WSAVA Nov 2021 Proceedings

Antiemetic agents 0132 Until recently the choices for antiemetic agents for use in cats with MEDICAL AND NUTRITIONAL THERAPY FOR pancreatitis was limited. Metoclopramide, a dopamine inhibitor, was most OSTEOARTHRITIS widely used. However, its effect on splanchnic perfusion remains in ques- C. Villaverde1, R. Palmer2 tion. Fortunately, several other antiemetic agents have become available. Ondansetron and dolasetron are 5HT3 antagonists and are very effective 1Fermoy/Ireland, 2Fort Collins/United States of America antiemetic agents in cats. Maropitant, an NK1 antagonist is highly effec- tive in cats and should be the first drug of choice as an antiemetic. Other therapeutic strategies Qualifications: In contrast to human beings, infectious complications of pancreatitis are Cecilia Villaverde rare in cats with pancreatitis. Also, even though such complications occur frequently in human pancreatitis patients, a clear advantage of antibiotic BVSc, PhD, DACVN, DECVCN use has not been demonstrated to date. Therefore, the use of antibiotic agents should be limited to those cases where an infectious complication cvillaverde@expertpetnutrition.com can be identified or is strongly suspected. Ross H. Palmer Many other therapeutic strategies, such as the administration of antiin- flammatory agents, trypsin-inhibitors (e.g., trasylol), platelet activating DVM, MS, DACVS factor inhibitors (PAFANTs), dopamine, antacids, antisecretory agents (i.e., anticholinergics, calcitonin, glucagon, somatostatin), or selenium, ross.Palmer@ColoState.edu and peritoneal lavage all have been evaluated in human patients with Osteoarthritis (OA) is a catabolic disease that affects the whole joint pancreatitis. organ, pain perception, cardiovascular fitness, and, ultimately, the whole patient. The painful patient is less active and loses muscle mass and Dopamine has been shown to be useful in preventing progression of cardiovascular fitness while gaining weight. Normal family routines are pancreatitis when administered to cats within 12 hours of initiating often disrupted. Effective joint health management must be directed at pancreatitis. While this time-limit would preclude dopamine to be effective the entire patient. in routine therapy of spontaneous pancreatitis, patients with pancreatitis that have to undergo anesthesia may benefit from treatment with dopa- Pet-owner engagement is necessary to gain their active involvement and mine during the procedure. development of treatment goals. Mild chronic pancreatitis Attaining & maintaining a lean body conformation through proper nutrition and feeding practices is the cornerstone of effective OA treatment. It is It should also be noted that many feline patients have mild forms of chron- also important for prevention: keeping dogs lean from weaning onwards ic pancreatitis. Often times these patients have concurrent conditions, reduces the risk of orthopedic disease1. Being overweight can both con- most notably IBD. Very little is known about appropriate therapy for these tribute to the development of OA and, for patients with pre-existing dis- animals and management is often limited to evaluation and treatment of ease, worsen its clinical presentation1, this can be due to both mechanical the concurrent condition and careful monitoring of the pancreatitis. Serum stress on the joints and the systemic inflammation status in obesity2. For calcium, triglyceride, cobalamin, and folate concentrations should always dogs with OA and that have a lean body condition score (BCS), portion be evaluated in these patients in order to identify any potential risk factors control should be adjusted to ensure weight maintenance throughout their that can potentially be addressed therapeutically. Also, the use of low fat life. A BCS of 4 or 5 out of 9 is the target (4 better for larger breeds, 5 in diets is recommended in these patients. cats). For patients with OA that are overweight, a weight loss plan should be initiated with a veterinary diet formulated for weight loss. These diets Over the last two decades a new form of pancreatitis, autoimmune are nutrient fortified, to help prevent marginal nutrient intakes while calo- pancreatitis has been described in humans. Autoimmune pancreatitis is rie restricting, besides being bulky and potentially more satiating vs main- characterized by a lymphocytic-plasmacytic infiltration of the pancreas. tenance diets. Even modest weight loss3 (without reaching ideal BCS) Human patients with autoimmune pancreatitis respond favorably to the can result in marked improvements in mobility and quality of life. Weight administration of corticosteroids. There are anecdotal reports of cats with loss rates recommended are 1-2% per week, although slower rates can be mild chronic pancreatitis responding to corticosteroids or cyclosporine. acceptable, especially if a veterinary weight loss diet cannot be used. However, further studies are needed before immunosuppressive therapy can be recommended for routine treatment of chronic pancreatitis in cats. An active lifestyle of regular activity that is moderated away from inter- mittent extremes is essential. This can be difficult for pet-owners because Reference it impacts their daily schedule, but that lifestyle shift often benefits the pet-owner as well. 1. Forman MA, Steiner JM, Armstrong PJ, et al. ACVIM consensus state- ment on pancreatitis in cats. J Vet Intern Med. 2021; 35. Therapeutic exercise and physical rehabilitation are key steps in convert- ing the osteoarthritic, overweight and sedentary dog to a lean, physically fit dog that is enthusiastic about activity again. Diets specifically formulated for the dog with OA can be useful in this condition, and there is some evidence of diets enriched in omega 3 fatty acids from fish oil (EPA and DHA) in improving mobility and clinical signs in dogs4 and (even though there is less evidence overall) in cats5. The proposed mechanism of action relates to the fact that omega 3 and 6 families compete for the same metabolic enzymes. Increasing omega 3 in the diet, especially EPA, can result in increased production of anti-inflam- matory eicosanoids, especially if combined with a low omega 6: omega 3 ratio, which would reduce eicosanoid production from arachidonic acid 201

13–15 NOVEMBER, 2021 (more pro-inflammatory). The rate of conversion of alpha-linolenic acid microparticles decay to inert tin. (the omega 3 precursor) is quite low, so providing EPA and DHA directly is more efficient; however, alpha-linolenic acid inclusion can also contribute Biologic therapies are gaining advocates. Platelet rich plasma (PRP), to the reduction of the 6 to 3 ratio. While there is no specific recommenda- an autologous concentration of platelets in a small volume of plasma, tion for the ratio, the EPA and DHA dose for OA ranges from 240-310 mg/ contains a concentration of critical growth factors that are secreted kg of metabolic body weight6. Using a diet enriched in these fatty acids to stimulate cellular proliferation, migration, differentiation and matrix is easier than supplementation separately and permits achieving higher synthesis. Several studies show favorable clinical outcomes as compared dosages. These diets can also include other joint nutraceuticals, although to positive and negative intra-articular controls in humans and dogs. There the evidence of their efficacy is still scarce. is substantial variation in PRP preparation and formulation, but affordable point-of-care preparation is certainly feasible. Nutraceuticals are controversial. Evidence of symptomatic benefit with chondroitin, glucosamine, manganese ascorbate and avocado soybean Mechanical therapies for OA include pulsed ultrasound and shockwave. unsaponifiables (ASU) in dogs is sparse, but demonstration of an- There is some evidence for the efficacy of shockwave therapy in OA ti-catabolic effects and joint protection in animal models is promising. management. Decreased OA pain scores and NSAID-reliance is reported in human, pla- cebo-controlled clinical trials. Undenatured type-II collagen may offer pain 1. Kealy RD, Olsson SE, Monti KL, Lawler DF, Biery DN, Helms RW, Lust G, relief comparable to NSAID-therapy and greater than that of glucosamine, Smith GK. Effects of limited food consumption on the incidence of hip chondroitin supplementation. dysplasia in growing dogs. J Am Vet Med Assoc. 1992 Sep 15;201(6):857- 63 Control of joint inflammation/pain is vital to restoration of mobility, com- fort and quality of life. NSAIDs have been the cornerstone of this strategy 2. Frye CW, Shmalberg JW, Wakshlag JJ. Obesity, Exercise and Orthopedic through their effects on prostaglandin E2 as a potent mediator of inflam- Disease. Vet Clin North Am Small Anim Pract. 2016 Sep;46(5):831-41. mation. Though the incidence of adverse reactions to COX-2 selective NSAID therapy is not fully known, significant adverse effects apparently 3. Marshall WG, Hazewinkel HA, Mullen D, De Meyer G, Baert K, Carmi- occur at a very low frequency when NSAIDs are properly administered.7 chael S. The effect of weight loss on lameness in obese dogs with osteo- arthritis. Vet Res Commun. 2010 Mar;34(3):241-53 Prostaglandin Receptor Antagonist NSAIDs (PRA’s) are designed to block the action of selected prostaglandins rather their production. PGE2 exerts 4. Roush JK, Cross AR, Renberg WC, Dodd CE, Sixby KA, Fritsch DA, Allen its nociceptive and inflammatory effects by binding to EP receptors in- TA, Jewell DE, Richardson DC, Leventhal PS, Hahn KA. Evaluation of the cluding EP4. Grapiprant targets PGE2 activity at the EP4 receptor. Adverse effects of dietary supplementation with fish oil omega-3 fatty acids on reactions associated with COX-inhibiting NSAIDs may also be seen with weight bearing in dogs with osteoarthritis. J Am Vet Med Assoc. 2010 Jan PRA’s. Grapiprant should not be used in cats. 1;236(1):67-73. All NSAIDs must be accurately dosed and should not be given concurrent- 5. Corbee RJ, Barnier MM, van de Lest CH, Hazewinkel HA. The effect ly with other NSAIDs or corticosteroids. Blood tests are performed prior to of dietary long-chain omega-3 fatty acid supplementation on owner’s any class of NSAID therapy and periodically throughout treatment. NSAIDs perception of behaviour and locomotion in cats with naturally occurring should be discontinued and immediate consultation be sought if adverse osteoarthritis. J Anim Physiol Anim Nutr (Berl). 2013 Oct;97(5):846-53. effects occur. 6. Bauer JE. Therapeutic use of fish oils in companion animals. J Am Vet Nerve growth factor (NGF), which circulates in high concentrations in Med Assoc. 2011 Dec 1;239(11):1441-51. OA-joints, is another potent pain signaling protein that represents a novel therapeutic target for treatment of joint pain and inflammation. Binding of 7. Monteiro-Steagall BP, Lascelles BDX. Systematic review of nonsteroidal free circulating NGF with species-specific monoclonal antibodies produc- anti-inflammatory drug-induced adverse effects in dogs. J Vet Intern Med es potent pain relief in OA-affected humans, dogs and cats.8 2013;27:1011-1019. Adjunctive systemic medications can augment NSAIDs in OA patients. 8. Enomoto M, Mantyh PW, Murrell J, et al. Antinerve growth factor mono- Amantadine acts via central N-methyl-D-aspartate receptor antagonism clonal antibodies for the control of pain in dogs and cats. Vet Rec 2018; and is often used with NSAIDs. Amantadine enhances mobility and the https://doi.org/10.1136/vr.104590 . ability to perform everyday activities in OA-dogs when used in combina- tion with NSAIDs as compared to NSAIDs alone. Gabapentin has analgesic 9. Budsberg SC, Torres BT, Kleine SA, Sandberg GS, Berjeski AK. Lack of properties though its mechanism of action is poorly understood. Sedation effectiveness of tramadol hydrochloride for the treatment of pain and is its most common adverse effect. Tramadol is a synthetic, central- joint dysfunction in dogs with chronic osteoarthritis. J Am Vet Med Assoc ly-acting, mu-receptor agonist that acts via inhibition of serotonin and 2018;252:427-432. norepinephrine reuptake. A placebo-controlled, cross-over study design found that use of tramadol alone failed to improve pain scores or limb 10. Donecker J, Fabiani M, Gaschen L, Aulakh KS. Treatment response in dysfunction in dogs with chronic OA as compared to placebo- or carpro- dogs with naturally occurring grade 3 elbow arthritis following intra-ar- fen-treatment.9 ticular injection of 117mSn (tin) colloid. PloS one 2021; https://doi. org/10.1371/journal.pone.0254613 Non-systemic OA therapy using a radio-isotope (tin-117m) in homoge- neous colloid suspension via intra-articular injection is an encouraging novel therapy for up to 1 year relief of OA pain in dogs.10 The tin-117m microparticle remains within the joint and emits low-energy conversion electrons with 0.3mm range of activity. This provides targeted therapy without systemic side effects. Circulating inflammatory macrophages and synoviocytes selectively engulf the microparticles and undergo apopto- sis by the conversion electron activity. Limited penetration of tin-117m preserved the integrity and functionality of non-synovial tissues such as bone, cartilage, tendons and ligaments in healthy dogs. Ultimately, the 202 WSAVA GLOBAL COMMUNITY CONGRESS

0133 Home-Prepared Diets – Cooked & Raw: HOMEMADE VS COMMERCIAL DIETS Home-prepared diets have grown in popularity over the last few years. For some pet owners, it is in response to concerns about the production of L. Weeth commercial diets, for others feeding home-prepared foods reinforces the human-animal bond, and for still others, a home-prepared diet is required Los Angeles/United States of America to manage a medical condition. Proponents of home-prepared foods claim that these diets are a safe and natural way to feed animals. It is true that Qualifications: fresh meat whether it is fed raw or cooked is palatable to most dogs and cats, can be highly digestible, and depending on the cut of meat selected Lisa Weeth is higher in fat than most dry kibbles. The result is an animal that readily eats its food, has low stool volume, and a shiny coat. These positives as- DVM, DACVIM (Nutrition) pects are often held up as “proof” of nutritional superiority to commercial foods while ignoring the potential negative consequences. weethnutrition@gmail.com Published reviews of the nutritional adequacy of home-prepared (cooked INTRODUCTION and raw) diet recipes in recent years found that less than half of the reci- pes used by the pet owners provided a complete and balanced source of Pet food recalls, human diet and nutrition trends, and a growing appreci- nutrients.1-4 Unless someone with veterinary nutrition training developed ation for the role of diet in health and disease has led pet owners to seek the diet, there are a few consistent deficiencies found in most home-pre- out diets they believe will “optimize” health in their companion animals. pared recipes irrespective of the ingredients used. Most home-prepared Feeding a complete and balanced diet is known to promote wellness in diets for dogs and cats are lacking a sufficient source of calcium; a dogs and cats, but it can be challenging for pet owners to evaluate their source of trace minerals (such as iodine, selenium, copper, and zinc); a options in the face of marketing efforts by manufacturers and retailers. source of linoleic acid; and a source of essential fat-soluble and water-sol- Owners then turn to veterinarians for guidance when making these deci- uble vitamins. While the perceived benefits of home-prepared diets are sions and it is important for veterinary professionals (both doctors and reinforced daily to the owner, nutrient deficiencies in adult animals are support staff) to understand not only nutrition concepts but benefits and insidious and can lead to long-term complications, which can vary from limitations of various diet options. Many owners, and some veterinarians, poor skin and coat health to chronic diarrhea, osteopenia, anemia, altered will advocate feeding home-prepared foods exclusively (raw or cooked, or drug metabolism, and hepatic lipidosis depending on the specific nutrients both) and either cite perceived health benefits or a general mistrust of the lacking in the diet. pet food industry, but these diets can have multiple nutrient deficiencies if not formulated correctly and these deficiencies can have long-term and The negative aspects of raw meat diets can be disastrous for the animals potentially fatal consequences for individual dogs or cats. It is important and the people in the household. Any raw meat ingredients can be a for veterinarians and supports staff to understand the benefits and risks potential source of parasitic and bacterial exposure, which can include of any given diet type and to help ensure that, no matter the diet selected, Neospora, Toxoplasma, Salmonella, E. coli, Campylobacter, and Crypto- the nutritional needs of the individual animal are being met. sporidium;5-8 raw and cooked bones specifically carry a risk of gastro- intestinal obstruction/perforation and oral trauma;9,10 and are a poor BASIC NUTRIENT REQUIREMENTS FOR DOGS AND CATS source of essential minerals (such as calcium, phosphorus, and magne- sium) due to the poor digestibility of larger bones within the canine and fe- Dogs and cats are both classified into the order Carnivora, but selective line digestive tract.11 Ultimately, the animal’s acceptance of a home-pre- pressures over the last 15,000-30,000 years have allowed dogs to adapt to pared diet does not change significantly when the meat is cooked or when an omnivorous diet, while cats remained obligate carnivores. Dogs, unlike more bioavailable sources of nutrients are used. cats, are able to taste sweet; can synthesize adequate amounts of taurine from the sulfur amino acid precursors methionine and cysteine; can split Commercial Diets: b-carotene found in fruit and root vegetables into two vitamin A subunits; and have the ability to convert linoleic acid (found in high concentrations Complete and balanced commercial diets (dry, moist, pasteurized or raw- in plant seeds and grains) into arachidonic acid. Based on genetic map- meat-based frozen or dehydrated) are designed to be fed as a sole source ping, domestic dog developed a series of adaptations that allowed them of nutrition to dogs and cats and include adequate amounts and ratios of to metabolize a more carbohydrate-rich diet compared to wild wolves. all essential nutrients. Nutrient levels are either formulated on an energy These metabolic adaptations have allowed domestic dogs to thrive on a basis (nutrient per 1000 kcal of diet) or on a Dry Matter basis (nutrient wide variety of plant and animal-based ingredients. per kg of food). Pet food formulation and labeling requirements may vary by region, but most countries have adopted guidelines recommended by Despite metabolic differences between dogs and cats, they have similar the European Pet Food Industry Federation (FEDIF) and the Association of requirements for specific essential amino acids, essential long-chain American Feed Control Officials (AAFCO). FEDIAF and AAFCO have estab- fatty acids, macrominerals, trace minerals, water-soluble vitamins, and lished model guidelines for the countries and states regarding pet food fat-soluble vitamins. Both dogs and cats can synthesize vitamin C in the labels, ingredient definitions, what can and cannot go into pet foods, and liver; neither species can synthesize vitamin D from UV exposure of skin; levels of specific essential nutrients required for a given life-stage. Any and both lack salivary amylase for the initial step in carbohydrate metab- pet food with a FEDIAF or AAFCO label of adequacy must have met these olism but have pancreatic amylases activity and glucose receptors on guidelines, though it is up to individual nations or states to regulate and enterocytes for further carbohydrate utilization. Altogether dogs require enforce these recommendations. Commercial diets will then be labeled 37 essential nutrients in their diets and cats require 41 and it is important as having gone through “feeding trials” to ensure nutrient adequacy or as that the diet selected and fed on a regular basis meets these ongoing having been “formulated” to meet these requirements. Commercially pro- nutritional needs. Food is the means of getting essential nutrients into the duced fresh-food diets (raw or cooked) still must meet industry labeling body and providing a complete and balanced diet that optimized health requirements and any diet or brand lacking this basic, required informa- and wellness for the individual dog or cat is more important than the form tion should be viewed with concern. that food takes. SUMMARY 203

13–15 NOVEMBER, 2021 Individual animals may vary in their response to specific commercially 0134 available diets and there is no one diet-that-fits-all. If an owner elects to feed a home-prepared diet they should be counseled on the risks of this TEACHERS ARE STRESSED TOO! TRAINING AND feeding strategy and cautioned that nutritionally-related disease can mim- SUPPORT FOR EDUCATORS ic other forms of chronic illness. Any animal eating a home-prepared diet should have at least an annual physical exam and health screening, in- M. Peterson cluding serum biochemistry (with T4), hematology, and urinalysis profiles. While blood work and urinalysis results will give you a general overview Washington,/United States of America of the animal’s health status, they will not pick out specific deficiencies or excesses. A complete diet history (all foods and supplements) should Qualifications: be collected from the owner at each visit. Any home-prepared diet recipes should be obtained from a reputable, trained source. As a member of their senior leadership team, Makenzie Peterson serves as the Director for Wellbeing at the American Association of Veterinary References Medical Colleges (AAVMC). She works to advance AAVMC’s strategic goal of fostering a culture of wellbeing throughout academic veterinary • Lauten SD, et al. Computer analysis of nutrient sufficiency of published medicine by promoting preventative systems-based initiatives. Maken- home-cooked diets for dogs and cats [abstract]. JVIM 2005; 19:476-477. zie provides subject-matter expertise on the science and application of evidence-based wellbeing practices, as well as the development and • Larsen JA, et al. Evaluation of recipes for home-prepared diets for dogs implementation of strategic organizational changes to improve the overall and cats with chronic kidney disease. JAVMA 2012; 240:532-538 wellbeing of academic communities. She speaks on a variety of wellbe- ing-related topics, and also currently serves on the Board of Directors • Heinze CR, et al. Assessment of commercial diets and recipes for for the Women’s Veterinary Leadership Development Initiative. Born and home-prepared diets recommended for dogs with cancer. JAVMA 2012; raised in Alaska, Makenzie graduated from the University of Utah with a 241:1453-1460. master’s degree in Health Promotion & Health Education and will complete her Doctorate of Social Work from the University of Southern California in • Stockman J, Fascetti AJ, Kass PH, and Larsen. Evaluation of recipes of 2022. home-prepared maintenance diets for dogs. JAVMA 2013;242(11):1500-5. Makenzie Peterson: mpeterson@aavmc.org • Strohmeyer RA, et al. Evaluation of bacterial and protozoal contami- Teachers are stressed too! Training and support for educators nation of commercially available raw meat diets for dogs. JAVMA 2006; 228(4):537-542. This presentation will provide participants with the current research results related to the Clinician Wellbeing Initiative: Faculty & Educator • Lejeune JT and Hancock DD. Public health concerns associated with Wellbeing - the first-ever U.S. faculty wellbeing study in the veterinary feeding raw meat diets to dogs. JAVMA 2001; 219:1222-1225. profession, identify potential implementation points and provide evi- dence-based approaches and recommendations for consideration. Envi- • Martinez-Anton L, et al. Investigation of the role of Campylobacter ronmental factors that impact wellbeing integration in veterinary medicine infection in suspected acute polyradiculoneuritis in dogs. JVIM 2018; will also be discussed. 32:352–360. • Investigation into an outbreak of Shiga toxin producing Escherichia coli (STEC) O157 PT 21/28 Stx2 in England, August 2017. Public Health England 17 October 2018. • Frowde PE, et al. Oesophageal disease in 33 cats. J Fel Med Surg 2011; 13:564-596. • Thompson HC, et al. Esophageal foreign bodies in dogs: 34 cases (2004-2009). JVECCS 2012; 22:253-261. • Delay J and Laing J. Nutritional osteodystrophy in puppies fed a BARF diet. AHL Newsletter. 2002; 6(2):23. 204 WSAVA GLOBAL COMMUNITY CONGRESS

0135 Dietary composition may favor growth or repression of certain species: E.g. prebiotics that stimulate growth of Clostridiales and Faecalibacteri- BACTERIAL GASTROINTESTINAL DISEASES OF PETS um. Dietary fat and sugars may suppress symbionts and promote growth AND THEIR PEOPLE of pathosymbionts: “Western diet” K. Simpson Intestinal Inflammation of any type How does dysbiosis develop? Ithaca/United States of America Does dysbiosis precede overt inflammation in a genetically predisposed host? Qualifications: Genes such as NOD2 and ATG16L have been associated with dysbiosis, but in and off itself the dysbiosis associated with genetic polymorphisms Kenneth W Simpson in the absence of inflammation, is not as extreme as that associated with inflammation. BVM&S, PhD, DipACVIM, DipECVIM Do good bugs suppress bad bugs? Yes! They can secrete products that suppress Gram negative paythosym- kws5@cornell.edu bionts e.g. Lactobacillus Mechanistically, inflammatory disorders of the intestinal tract, categorized Do bad bugs suppress good bugs? as “inflammatory bowel disease (IBD)” or “chronic enteropathy”, are con- Yes! They can directly inhibit the growth of resident symbionts . E.g. sidered a consequence of dysregulated interplay between host-suscepti- Klebsiella bility and immunity, the enteric microbial and chemical microenvironment, Does inflammation in and of itself cause dysbiosis?(Figure 1) and environmental “triggers”, but the specific interactions that promoting Yes! It is has been clearly shown that inflammation in the absence of ge- chronic inflammation are unresolved. The microbiome of the inflamed in- netic susceptibility can create marked dysbiosis. The degree of dysbiosis testines in people, dogs, cats and mice is characterized by the expansion is related to the severity of inflammation of ‘aggressive’ bacteria such as Proteobacteria and mucosa-associated E. coli, relative to depletion in ‘protective’ bacteria such as Firmicutes. This Figure 1. Inflammation Drives Dysbiosis in the absence of genetic sus- imbalance in the composition of the enteric microbiome is referred to as ceptibility: Genetic defects associated with IBD impact the threshold and dysbiosis. magnitude of floral shifts Dysbiosis across species Why do beneficial bacteria become depleted in the inflamed intestine? Altered mucosal niche? Chronic enteropathies and Lymphoplasmacytic enteritis in dogs and cats Loss of mucus, loss of surface area (villus atrophy), loss of metabolic capacity of a related symbiont, loss of nutrients/metabolites associated Expansion of proteobacteria and reduction in beneficial firmicutes with a healthy flora Inability to utilize inflammation associated substrates Granulomatous colitis in dogs Lack of metabolic plasticity to adapt to a changing intraluminal microen- vironment Comparative sequence based analysis reveal dysbiosis characterized by Direct attack by proliferating pathosymbionts enrichment in E.coli and depletion in Clostridiales. I situ analysis indicates an association with intracellular E.coli in PAS+ GC in French bulldogs, Boxers and mastiff cluster breeds. HGE/AHDS HGE/AHDS associated with Clostridium spp (culture and molecular stud- ies) and most recently NetF producing C.perfringens Crohn’s disease Expansion of proteobacteria such as AIEC E.coli and reduction in benefi- cial firmicutes such as F.prausnitzii What causes dysbiosis? Genetic makeup Defects impacting Paneth cell function E.g. ATG16L, NOD2, Xbp1,IRGM Defects associated with innate immunity E.g. NOD2, CD48/SLAM, NCF Defects associated with barrier function and endoplasmic reticulum stress E.g. Sel1L, AGR2 Antimicrobial therapy Metronidazole, fluroqionolones? Diet 205

13–15 NOVEMBER, 2021 Why do “bad bugs” proliferate in the inflamed intestine? a selective increase in invasive Escherichia coli of novel phylogeny relative to depletion of Clostridiales in Crohn’s disease involving the ileum. Loss of surveillance from good bacteria ISME J 1(5):403-418. Resident beneficial bacteria such as Lactobacillus can secrete products • Craven MD, et al. Inflammation Drives Dysbiosis and Bacterial Invasion that antagonize the growth of proteobacteria such as E.coli in Murine Models of Ileal Crohn’s Disease. PLOSOne 7(7):e41594. Epub 2012 Jul 25. Ability to adapt to the inflamed environment • Dogan B, et al. Inflammation-associated adherent- invasive Escherichia Dysbiotic bacteria are frequently adept at resisting oxidative and osmotic coli are enriched in pathways for use of propanediol and iron and M-cell stress and injurious bile salts translocation. Inflammatory bowel diseases. 2014; 20(11):1919-32. Ability to utilize inflammation associated substrates • Dogan B, Zhang S, Kalla SE, Dogan EI, Guo C, Ang CR, Simpson KW.Anti- biotics (Basel). 2020 Aug 25;9(9):540. doi: 10.3390/antibiotics9090540. Dysbiotic bacteria have a portfolio of metabolic pathways that enable Molecular and Phenotypic Characterization of Escherichia coli Associated them to utilize many different nitrogen and carbon sources. with Granulomatous Colitis of Boxer Dogs. Many Gram negative dysbiotic bacteria are enriched in pathways that • Dogan B., ef al. Multidrug resistance is common in Escherichia coli enable them to use chemicals that are increased in the inflamed gut. E.g associated with ileal Crohn’s disease. Inflamm Bowel Dis. Apr 16. doi: ethanolamine, glutamine. 10.1002/ibd.22971. Dysbiotic bacteria can be seen feasting on cellular material associated • Hayward JJ, et al.Complex disease and phenotype mapping in the with IBD and the magnitude and type of dysbiosis may correlate with domestic dog. Nat Commun. 2016 Jan 22;7:10460. levels of host DNA (tissue damage) in feces. • Hoehne SN, et al.Identification of Mucosa-Invading and Intravascular Opportunities for therapeutic intervention Bacteria in Feline Small Intestinal Lymphoma.Vet Pathol. 2016 Sep 14. pii: 0300985816664792. Elimination of known pathogens (bacteria, algae, protozoa etc) • Janeczko S, et al . The relationship of mucosal bacteria to duodenal Antimcrobials , bacteriophage, environmental modification histopathology, cytokine mRNA, and clinical disease activity in cats with inflammatory bowel disease.Vet Microbiol 128(1-2):178-93. Dietary modification • Manchester AC, Dogan B, Guo Y, Simpson KW.J Vet Intern Med. 2021 avoidance of foods inducing clinical signs and intestinal inflammation e.g. Jan;35(1):150-161. doi: 10.1111/jvim.15995. Epub 2020 Dec 15. Esche- food responsive enteropathy. Prebiotics to support probiotics. richia coli-associated granulomatous colitis in dogs treated according to antimicrobial susceptibility profiling. Eradicate pathosymbionts • Simpson KW, et al Adherent and Invasive Escherichia coli are Asso- Antibiotics, bacteriophage, modify luminal environment, ciated with Ulcerative Colitis of Boxer Dogs. Infection and Immunity 74(8):4778-92. Selectively restrict growth and virulence of pathosymbionts • Suchodolski JS, et al. The fecal microbiome in dogs with acute e.g., inhibit growth by modifying luminal microenvironment, antagonzing diarrhea and idiopathic inflammatory bowel disease. PLoS One. metabolism, reduce motility and virulence gene expression, block adhe- 2012;7(12):e51907. sion and invasion • Viladomiu, M, et al. Functional characterization of IgA-targeted E. coli Anti-inflammatory agents in Crohn’s Disease-associated Spondyloarthritis Links Mucosal Immunity with Systemic Inflammation. Science Translational Medicine. Sci Transl Prednisolone at dose to restore epithelial function and reduce inflamma- Med. 2017 Feb 8;9(376). tion without immunosuppression, ASA (dual effect on bacteria and host), rifaximin (dual effect on bacteria and host) Immunomodulation Reduce or eliminate inflammation that is driving dysbiosis Enhance protective immunity Replenish beneficial symbionts Probiotics: “live microorganisms, which when administered in adequate amounts, confer a health benefit on the host” Prebiotics Postbiotics Synbiotics Microbiome transplantation References / further reading: • Arthur JC, et al. 2012. Intestinal inflammation targets cancer-inducing activity of the microbiota. Science (New York, N.Y.). 2012; 338(6103):120- 3. • Baumgart M, et al. Culture independent analysis of ileal mucosa reveals 206 WSAVA GLOBAL COMMUNITY CONGRESS

0136 rize 2 key studies regarding the potential effects of this probiotic in the management of different canine or feline diarrheal syndromes. Additional USE OF PROBIOTICS IN THE MANAGEMENT OF studies with other probiotics or synbiotics will be presented in the presen- DIARRHEA IN PETS AND THEIR PEOPLE tation. M. Lappin In the first study, it was hypothesized that cats and dogs housed in an animal shelter that were fed E. faecium strain SF68 would have decreased Fort Collins/United States of America episodes of diarrhea and improved fecal scores compared with untreat- ed cats and dogs in the same environment.7 The cats were housed in Qualifications: two different rooms and the dogs were housed in two different rooms in a northern Colorado Animal Shelter. The cats and dogs were all fed a Michael R. Lappin standardized diet by species. Animals in one room were supplemented daily with E. faecium strain SF68 and animals in the alternate room were DVM, PhD, DACVIM (Small Animal Internal Medicine) supplemented daily with a placebo. To reduce risk of a room influence on study results, the room in which cats or dogs were being supplemented mlappin@colostate.edu with E. faecium strain SF68 was switched after one month, with a one- Probiotics are live microorganisms that when administered in adequate week washout period. Prior to cleaning the room each morning, feces in amounts confer a beneficial health effect on the host. When combined the cage of each animal was scored by a masked investigator using the with a prebiotic like inulin or psyllium the product is called a synbiotic. Purina Fecal Scoring System for Dogs and Cats (fecal score of 5, 6, or 7 There have been many studies and reviews of the effects of probiotics on considered diarrhea). The percentages of dogs or cats with diarrhea of > 2 the health of humans, but fewer in small animals.1-3 Evidence supporting days duration were calculated over the course of the study. A generalized the use of probiotics is generally strongest for managing gastrointestinal linear mixed model using a bionomial distribution with treatment being a syndromes such as acute or chronic diarrhea due to infectious diseases fixed effect and the room being a random effect was used to assess for or inflammatory bowel disease. There is also some evidence that probiot- statistical differences between treatment groups. Presence of parasites ics might be beneficial for mitigating antibiotic-associated vomiting or di- was included as a covariate. Significance was defined as p < 0.05. arrhea.4-6 It is known that some probiotics help balance the endogenous microbiota and that some can inhibit replication of pathogenic bacteria. Diarrhea prevalence rates were low for all dogs in the study, so statistical Some of the proposed mechanisms of action include competition for differences were not detected. However, the percentage of cats with diar- essential nutrients or receptor sites, binding of pathogenic bacteria, and rhea > 2 days was 7.7% for the probiotic group and 20.7% for the placebo production of inhibitory substances. There is also evidence that some pro- group. This result was significantly different (p = 0.0297) and suggests biotics induce immune modulating effects with potential benefits for the that administration of E. faecium strain SF68 to cats housed in shelters management of inflammatory bowel disease, atopy, or infectious diseases may lessen the numbers of days with diarrhea. As this was a short-term with systemic involvement (e.g., feline herpesvirus-1; FHV-1). study, this beneficial effect was likely from probiotic influences on intesti- nal flora rather than systemic immune enhancing effects. Infectious diseases are common in small animals, so the potential benefi- cial effects of probiotics could impact veterinary practice significantly. It In the second research study, at total of 16 healthy, young-adult research is also now known that some probiotics can beneficially influence innate colony cats fed a commercial dry food were administered amoxicil- and acquired immunity systemically. Not all of the methods by which lin-clavulanate (Clavamox) at 62.5 mg/cat twice daily.8 Using a standard- probiotics modulate the immune system have been characterized and it ized fecal scoring system, trained, masked personnel scored feces every is likely that these effects vary by probiotic. Thus, a clinical effect that is twelve hours, with scores >4 considered diarrhea. Amoxicillin-clavula- shown to be induced by one probiotic may not be induced by others, even nate as discontinued if fecal scores were >4 for 2 days. Cats were then in the same genus and species of bacteria. For example, there are many randomized into 2 treatment groups, one group was supplemented with a strains of Enterococcus faecium, but positive clinical effects in dogs or symbiotic that consists of E. faecium stain SF68 with psyllium (FortiFlora cats have only been shown with the E. faecium strain SF68. SA) in 15g of canned food once daily and the other group supplemented with the palatability enhancer from the synbiotic in 15g of canned food While probiotic use is generally considered safe, consumers should ask once daily. companies marketing probiotics for the product’s safety information. One of the other major issues concerning probiotic use in small animal Diarrhea was less severe overall in the synbiotic group, with 24.5% of practice is quality control. In recent veterinary studies, the majority of fecal samples scored >5, compared with 48.9% in the control group (p = products claiming to contain probiotics generally did not meet the label 0.0132). Time to diarrhea resolution was 4.5 periods from initiation of claim when evaluated.Other unresolved issues for probiotic use in small treatment in the probiotic group, compared with 6.5 periods in the control animals is the optimal number of bacteria to be used and whether there group (p = 0.472). Clinical resolution of diarrhea was achieved in all cats are clinical benefits to having multiple strains of bacteria in a product. in the synbiotic group. Two cats in the control group had a rescue protocol Since each bacterium in a probiotic can have unique effects, products instituted for diarrhea that failed to resolve during the study period. containing multiple bacteria actually may have competing mechanisms of action lessening potential beneficial effects. These results indicate that supplementing this symbiotic to cats with diarrhea provoked by administration of amoxicillin-clavulanate reduces There are several veterinary probiotic products marketed in the United severity of diarrhea and may decrease time to resolution. States that have been shown to be safe, meet label claims, and have clin- ical studies supporting potential beneficial effects, including E. faecium References strain SF68 (FortiFlora®-Nestlé Purina PetCare). Recently, studies evalu- ating gastrointestinal effects of other commercially available probiotics 1. De Vrese M, Scherezenmeir J. Probiotics, prebiotics, and synbiotics. or synbiotics have been published and can be used to help veterinarians Adv Biochem Eng Biotechnol 2008;111:1-66. choose which products to make available to their clients. 2. Schmidt SS. Value of probiotics in canine and feline gastroenterology. Enterococcus faecium strain SF68 (NCIMB 10415) was originally isolated Vet Clin Small Anim 2021:51:171-217. from the feces of a healthy baby and was initially shown to inhibit the growth of a number of enteropathogens. In this proceedings, I will summa- 3. Jugan MC, Rudinsky AJ, Parker VJ, et al. Use of probiotics in small 207

13–15 NOVEMBER, 2021 animal veterinary medicine. J Am Vet Med Assoc 2017;250:519-528. 0137 4. Torres-Henderson C, Summers S, Suchodolski J, et al. Effect of Entero- NOT CUSHING’S DISEASE: DIAGNOSIS AND coccus faecium strain SF68 on gastrointestinal signs and fecal microbi- MANAGEMENT OF ADRENAL TUMORS IN THE DOG ome in cats administered amoxicillin-clavulanate. Top Companion Anim AND CAT Med 2017;32:104-108 A. Hohenhaus 5. Stokes JE, Price JM, Whittemore JC. Randomized, controlled, crossover trial of prevention of clindamycin-induced gastrointestinal signs using a New York City/United States of America synbiotic in healthy research cats. J Vet Intern Med. 2017;31:1406-1413. Qualifications: 6. Whittemore JC, Stokes JE, Price JM, Suchodolski JS. Effects of a synbiotic on the fecal microbiome and metabolomic profiles of healthy Ann Hohenhaus research cats administered clindamycin: a randomized, controlled trial. Gut Microbes. 2019;10:521-539. DVM, Diplomate, ACVIM (Oncology and Small Animal Internal Medicine) 7. Bybee SN, Scorza AV, Lappin MR. Effect of the probiotic Enterococcus Member, WSAVA Oncology Working Group faecium SF68 on presence of diarrhea in cats and dogs housed in an animal shelter. J Vet Intern Med. 2011;25:856-860. ann.hohenhaus@amcny.org Adrenal tumors represent a small number of tumors in dogs and cats, but 8. Kiene JA, Dobesh KC, Gagne J, Lappin MR. Use of a Synbiotic for they can cause significant paraneoplastic effects. Autonomous hormone Treating Antibiotic-induced Diarrhea in Cats. Abstract. American College production or complications due to the presence of an abdominal mass of Veterinary Internal Medicine Annual Forum 2020. Virtual Poster with vascular invasion can clue veterinarians into the presence of an adrenal tumor in a canine or feline patient. This presentation will focus on tumors of the adrenal gland that do not produce cortisol as Cushing’s disease or hyperadrenocorticism is a topic extensively covered elsewhere. Adrenal gland surgery will be covered in a separate lecture at WSAVA 2021 by Dr. Nicholas Bacon. Classification of adrenal tumors Adrenal tumors can be classified by multiple different schemes including: Anatomic location of tumor origin – cortex, medulla or metastatic Symptomatic or Asymptomatic (Incidentaloma) Hormone production – catecholamines versus steroid hormones Cancer metastatic to the adrenal glands is the most common type of cancer identified at necropsy, occurring in 26% of dog necropsies and 60% of cat necropsies. Addison’s disease from adrenal metastasis is rare but has been reported in both dogs and cats. The adrenal incidentaloma is a common finding in clinical practice and accounts for about 50% of adrenal tumors arising from the adrenal medulla and cortex. An incidentaloma is a tumor found incidentally during a diagnostic evaluation for an illness such as lower urinary tract signs, elevated liver enzymes or chronic kidney disease. Approximately 4% of abdominal ultrasounds and 9% of abdominal CT scans identify an adrenal incidentaloma. Adrenal tumors of the medulla are called pheochromocytomas and can make catecholamine hormones. Tumors of the adrenal cortex can make a variety of hormones including estrogen, testosterone or aldosterone and cortisol. Clinical signs of canine adrenal tumors About 50% of adrenal tumors are clinically silent. The clinical signs of adrenal tumors that do not produce cortisol are very nonspecific. Signs depend on if the tumor is large and palpable, invasive, and causes venous obstruction, ascites or is producing hormones. The most common clinical signs found in dogs with pheochromocytoma are weight loss, anorexia, depressions weakness/collapse. Sudden death from arrhythmias or hemoabdomen also occur. Dogs with adrenal cortical tumors producing hormones show clinical signs related to hormone production such as urine spraying, estrus behavior or weakness from hypokalemia. Diagnostic evaluation of canine patient with an adrenal gland tumor 208 WSAVA GLOBAL COMMUNITY CONGRESS

Routine blood tests may be normal or if the adrenal tumor is producing hypertension. Abdominal ultrasound and CT scans are useful for surgical a hormone such as aldosterone, postassium can be profoundly low. planning to determine extent of vascular invasion by the tumor. A standard Measurement of blood pressure is a key component of the diagnostic endocrine testing protocol for cats with adrenal tumors has not been rec- evaluation of a dog with hypertension since hypertension is common in ommended, but tests to consider are measurement of plasma aldosterone dogs with pheochromocytoma and cortisol producing tumors. Abdominal or an ACTH stimulated adrenal panel or a low dose dexamethasone sup- ultrasound and CT scan are useful for surgical planning to determine pression test. Plasma aldosterone reported in one study was greater than extent of vascular invasion by the tumor. Occasionally nephrectomy is 1047 ng/dl in all cats (reference range 194-388 ng/dl). Scant information required for complete tumor removal and if nephrectomy is anticipated, an suggests testing metanephrine and normetanephrine may be useful feline evaluation of individual kidney glomerular filtration rate would be useful. A patients suspected of having a pheochromocytoma. standard endocrine testing protocol for pets with adrenal tumors has not been recommended, but evaluations of cortisol, aldosterone and catechol- Surgical treatment amine production should be carefully chosen. Currently the tests of choice for catecholamine overproduction in dogs are urine metanephrine: creat- Surgery is the treatment of choice for feline adrenal tumors. Following inine ratio and the urine normetanephrine: creatinine ratio. Metanephrine adrenalectomy, survival of cats can be prolonged, and the median survival and normetanephrine are metabolites of epinephrine and norepinephrine. was reported to be 61 weeks (range 0-149 weeks). Metastasis occurred in While it sounds risky, fine needle aspiration cytology of the adrenal glands 2/33 cats. In the same study of feline adrenal tumors, 17/33 were carcino- has been shown to have an accuracy of 90-100% in differentiating cortical ma, 13 adenoma and 3 pheochromocytoma. from medullary tumors and also to be relatively low risk. Medical management Surgical treatment Because cats with adrenal tumors are not always good surgical candi- Surgery is the treatment of choice for canine adrenal tumors and carries dates, a few reports of medical management have been published. Cats the possibility of long-term tumor control. Surgery has the best outcome diagnosed with hyperaldosteronism were treated with amlodipine for when the tumor is small and has not invaded into the nearby blood vessel. hypertension, spironolactone to counteract aldosterone and potassium Most, but not all surgeons recommend phenoxybenzamine be adminis- supplementation. Survival was reported to be 1-2 years. If a pheochromo- tered for 2 weeks prior to surgery, because of an improved outcome. The cytoma is diagnosed, medical management should consist of amlodipine, excised adrenal gland should be submitted for histopathological exam- phenoxybenzamine and atenolol. ination after excision to help give an accurate prognosis to the owner and plan post-surgical follow up. Adrenal tumors are roughly about equally References divided between adenoma, adenocarcinoma and pheochromocytoma. One year survival is > 80% for all histologic tumor types. Approximately of Daniel G, Mahony OM, Markovich JE, et al. (2016) “Clinical findings, malignant adrenal tumors 20% metastasize. diagnostics and outcome in 33 cats with adrenal neoplasia (2002-2013).” Feline Med Surg. Feb;18(2):77-84. Medical management Arenas C, Pérez-Alenza D, Melián C. (2013) “Clinical features, outcome Because dogs with adrenal tumors are not always good surgical candi- and prognostic factors in dogs diagnosed with non-cortisol-secreting dates, a few reports of medical management have been published. One adrenal tumours without adrenalectomy: 20 cases (1994-2009).” Vet Rec. study of non-cortisol producing tumors found dogs lived a median of Nov 23;173(20):501. 17.8 months following diagnosis. Metastasis and tumor size > 50 mm indicated a poor prognosis. Dogs with a cortisol producing adrenal tumor Schwartz P, Kovak JR, Koprowski A, et al. (2008) “Evaluation of prognos- did not live as long and were reported to have a median survival of 277 tic factors in the surgical treatment of adrenal gland tumors in dogs: 41 days if treated with mitotane or trilostane. Limited data is available on the cases (1999-2005).” J Am Vet Med Assoc. 232(1):77-84. efficacy of chemotherapy for malignant adrenal tumors. One study of five dogs diagnosed with inoperable or metastatic pheochromocytoma treated Cook AK, Spaulding KA, Edwards JF. (2014) “Clinical findings in dogs with toceranib phosphate, demonstrated stable disease (4 dogs) and with incidental adrenal gland lesions determined by ultrasonography: 151 partial response (1 dog). cases (2007-2010).” J Am Vet Med Assoc. 244(10):1181-5. Clinical signs feline adrenal gland tumors Baum JI, Boston SE, Case JB. (2016) “Prevalence of adrenal gland masses as incidental findings during abdominal computed tomography in dogs: Adrenal gland tumors are much less common in cats than in dogs. About 270 cases (2013-2014).” J Am Vet Med Assoc. 249(10):1165-1169. 25% do not secrete hormones; those tumors that do secrete hormones are most likely to secrete aldosterone, but sex hormone production from fe- Gilson SD, Withrow SJ, Wheeler SL, et al. “Pheochromocytoma in 50 dogs.” line adrenal tumors has been described. Cats with excessive aldosterone (1994) J Vet Intern Med. 8(3):228-32. production are typically hypokalemic and hypertensive. Some cats present for blindness due to hypertension. Less than 10 cases of pheochromocy- Barthez PY, Marks SL, Woo J, et al. (1997) “Pheochromocytoma in dogs: toma have been reported in cats and clinical signs are poorly character- 61 cases (1984-1995).” J Vet Intern Med. 1997 Sep-Oct;11(5):272-8. ized. Herrera MA, Mehl ML, Kass PH, et al. (2008) Predictive factors and the Diagnostic evaluation of feline patient with an adrenal gland effect of phenoxybenzamine on outcome in dogs undergoing adrenalecto- tumor my for pheochromocytoma. J Vet Intern Med. 22(6):1333-9. In cats with an aldosterone producing tumors, median serum potassi- Quante S, Boretti FS, Kook PH, et al. (2010) “Urinary catecholamine and um concentration was 3 mEq/L demonstrating the effects of excessive metanephrine to creatinine ratios in dogs with hyperadrenocorticism or aldosterone production. No other consistent laboratory findings have been pheochromocytoma, and in healthy dogs.” J Vet Intern Med. 24(5):1093-7. reported. Blood pressure is a key component of the diagnostic evalua- tion of a cat with an adrenal tumor since hyperaldosteronism results in Pey P, Diana A, Rossi F, Mortier J, et al. (2020) “Safety of percutaneous ultrasound-guided fine-needle aspiration of adrenal lesions in dogs: Per- ception of the procedure by radiologists and presentation of 50 cases.” J Vet Intern Med.34(2):626-635. 209

13–15 NOVEMBER, 2021 0138 mere presence of an adrenal mass is not in itself an indication, as many are found incidentally, and can be followed by ultrasound for several SURGICAL APPROACHES TO ADRENAL TUMORS months or longer without a significant change in growth. Evidence of invasion, rapid growth, obvious paraneoplastic signs, or clinical signs due N. Bacon to the physical presence (pain, ascites) are all indications that surgery is warranted. Guildford/United Kingdom If there are no clinical signs attributable to the mass, and there is no Qualifications: local invasion, then it is quite acceptable to re-ultrasound in a month and determine rate (or lack) of growth before committing the dog and owner Nicholas James Bacon to surgery. MA VetMB CertVR CertSAS DipECVS DACVS FRCVS CT imaging is recommended wherever possible when surgery is being considered or if vena cava invasion is suspected or known. A CT more ACVS Founding Fellow (Surgical Oncology) accurately delineates extent of tumour thrombus within the vena cava, phrenicoabdominal veins and involvement or displacement of the renal RCVS Specialist in Small Animal Surgery (Surgical Oncology) vessels, important for surgical planning. The CT will also identify any obviously enlarged lymph nodes that can be inspected or excised after ad- nickb@fitzpatrickreferrals.co.uk renalectomy. A high quality CT allows for accurate pre-operative planning Each canine adrenal gland consists of the outer cortex and the central of where tourniquets need to be placed, how many need to be used, likely medulla. The cortex is responsible for producing aldosterone, glucocorti- involvement of the kidneys (esp left renal vein), muscular invasion, and coids and sex hormones. Tumours of the medulla secrete catecholamines importantly early detection of nodal metastasis and lung metastasis. The and the most common tumour is the pheochromocytoma. There is little exact likelihood of metastasis varies depending on the source read, from sex or breed consistency with adrenal tumours, although not surprisingly 0-50%, but an attempt should be made to rule it out prior to surgery. dogs tend to be older. Glucocorticoid-secreting tumours (Cushingoid) tend to be seen in larger bred dogs. Adrenal tumours are often functional and Pre-op stabilization for functional cortical tumours is not normally neces- clinical signs relate to the hormones they produce. 41% of tumours arise sary although some surgeons will prescribe trilostane or mitotane before in the cortex and of these 10-20% invade the vena cava. 32% of adrenal tu- excision of a functional cortical tumour. Before excising a suspected mours are pheos but 30-50% invade the vena cava. This might be because pheochromocytoma however, phenoxybenzamine (0.6mg/kg po BID for the central location and proximity to the phrenicoabdominal vein allows a median of 20 days) has been associated with a lower morbidity, as is for tumor to grow down this into the cava. 27% of adrenal tumours are decreased age, lack of intra-operative arrhythmias and decreased surgery metastatic, with metastasis in decreasing order of frequency: carcinoma time (likely linked to increased surgical familiarity and availability of expe- highest incidence (pulmonary CA, mammary CA, prostatic CA, gastric CA, rienced surgical assistance). pancreatic CA), melanoma, histiocytic sarcoma, haemangiosarcoma, TCC, MCT, Lymphoma, OSA, SCC, leiomyosarcoma, mesothelioma, islet cell The exact techniques for adrenalectomy will be covered in the lecture. tumor, CSA, cholangiosarcoma, renal CA, FSA, Nasal CA, C-cell tumor, anal This will include simple excisions, dealing with invasion of the phrenicoab- sac adenoCA, liposarcoma, sweat gland CA, granulosa cell tumour dominal vein, renal vein and/or vena cava, and a paracostal approach for difficult right-sided tumours invading the liver. Standard operating instru- Presentation is variable. Most present for paraneoplastic signs if function- ments are used with the addition of vascular clamps (e.g. Satinskys), long al. These include; dissecting instruments and DeBakey forceps, and equipment available to prepare Rumel tourniquets intra-operatively. Functional cortical tumours Bilateral adrenalectomy is to be considered in cases with bilateral, often Glucocorticoid-secreting tumours; Cushingoid signs - polyuria/polydipsia, asymmetrical enlargement. Both adrenals should be removed in a single polyphagia, pot belly, thin skin procedure with dexamethasone being given pre-operatively and DOCP started intra-operatively to counter the inevitable Addisonian compli- Aldosterone-secreting tumours (Conn’s syndrome); muscle weakness cations. These patients can do very well, often living months-years on through hypokalaemia, sudden onset blindness through hypertension from supplemental therapy. hypernatraemia Post-operative management post functional adrenalectomy is not as many Functional medullary tumours consider a roller-coaster of de-stabilisation, but only as long as patients have been appropriately stabilised before surgery, surgery was well Catecholamine secretion leads to weakness, collapse, weight loss, anxi- planned and executed, an experienced critical care team is available and ety, panting, depression, hypertension, sudden-onset blindness due consideration and pre-emptive treatment given for potential compli- cations. Many cases have uneventful recoveries and leave after 48 hours Diagnosis of adrenal tumours is otherwise difficult, especially if non-func- under observation, but the worst can be affected by thrombo-embolic tional. The majority will not be visible on abdominal radiographs unless disease, persistent endocrine disease from functional metastasis, acute large. Approximately 10% are calcified. Many are found on abdominal renal failure from temporary renal pedicle occlusion during surgery often ultrasound, which raises a dilemma as to whether this mass is responsible compounded by concurrent nephrectomy, haemorrhage, pancreatitis, ileus for the clinical signs being investigated, or if it incidental. Evidence of in- and cardio-vascular and electrolyte abnormalities. vasion into local structures including the kidney and vena cava confirm the mass is malignant and so increase the index of suspicion that the mass Long-term outcome can be excellent following adrenalectomy, with a is a significant finding. Clinical signs with adrenal tumours (especially median survival long over a year to be expected, regardless of tumour his- pheos) can be vague and intermittent, and physical examination findings togenesis. Metastasis is not commonly documented and local recurrence can be variable. Abnormalities in laboratory tests are often nonspecific is unusual. Often the cause of death is not adrenal tumour-related, rather and not hugely helpful. These are typically older dogs and so many have another old age disease. concurrent diseases that complicate the overall picture. Post operative care – Bilateral Adrenalectomy Whether or not an adrenal tumor needs to be removed depends on a num- ber of factors, not counting cost, surgeon familiarity with the anatomy, and availability of intra-operative and post-operative high-end care. The 210 WSAVA GLOBAL COMMUNITY CONGRESS

Bilateral adrenalectomy is considered when bilateral asymmetric adre- 0139 nomegaly is observed. Adrenomegaly in itself is not an indication for immediate surgery, as many tumors are incidentally found and progress HOW I TREAT POSTOPERATIVE DELIRIUM/ slowly or not at all. The situation changes however with an enlarging DYSPHORIA mass, a mass over 3cm in diameter, or if a functional adrenal disease is suspected. T. Grubb Given that either one or both adrenal masses could be a pheochromocyto- Uniontown/United States of America ma, even in patients with hyperadrenocorticism, it is sensible to pre-treat all bilateral adrenalectomies with phenoxybenzamine prior to surgery, at Qualifications: a dose of 0.6mg/kg by mouth twice daily ideally for at least 7-10 days. Just as with unilateral disease, surgery is planned with a CT scan to help Tamara Grubb DVM, PhD, Diplomate ACVAA, President-Elect IVAPM, Fear identify the relative involvement of the phrenico-abdominal veins, the Free Level 3 Certified cava, the renal veins (especially the left) and any local invasion into the Recovery is often the most dangerous phase of anesthesia and the mor- liver, typically the caudate lobe from right-sided invasion. tality rate during this phase is higher than that of other phases (Brodbelt 2009). Patient status generally falls into one of 3 categories during The surgical technique for bilateral adrenalectomy does not differ from recovery: 1) Normal recovery, no treatment needed, 2) Dysphoric or painful two individual procedures. recovery, trouble-shoot to determine cause, analgesia and/or sedation may be needed, or 3) Excessively long recovery, attentive monitoring and Intra-operatively, prior to the second adrenal being removed, DOCP is support required and reversal drugs potentially needed. Follow these injected (SQ) at a dose of 2.15 mg/kg (range 1.9-2.4mg/kg), along with steps to determine/correct the cause of dysphoric/painful recoveries: dexamethasone SP (intravenously) at a dose of 0.20mg/kg (range 0.02- 0.40mg/kg). Determine emergency causes first. The primary emergent cause of delir- ium in recovery would be inability to breathe. Correct any /gas exchange On recovery the dexamethasone SP is repeated at the same dose every 24 issues. Often repositioning the head and administering supplemental hours until the dog is eating and this is then switched to oral prednisolone oxygen will correct the problem. If necessary, re-anesthetize and intubate at a dose of 0.25mg/kg every 12 hours. This is decreased to the long-term until patient cause can be determined. maintenance dose of 0.25mg/kg/d over 1-2 weeks post-operatively. Hyperthermia can also cause delirium in recovery. Take body temperature In the immediate post-operative period, electrolytes are measured every and start cooling procedures (ice, fan, etc.) if the patient is hyperthermic. 12 hours for 48-72 hours until it is clear that K and Na are stable and are not trending up and down respectively. If this occurs (rarely) then an Determine if the patient behavior is pain or dysphoria or fear additional dose of DOCP at 0.5mg/kg can be given. One of the many difficulties during recovery is differentiation of the Following discharge, electrolytes should be monitored every 7 days post effects of pain from ‘emergence delirium’ or excitement caused by the DOCP for the first month then at 48 hour intervals starting approximately anesthetic drugs themselves or fear/anxiety. day 22 post DOCP with the second dose of DOCP given once K and/or Na can be seen to be trending outside the normal range. This gives the Pain can cause excitement as the patient regains consciousness, result- patient DOCP interval and it is idiosyncratic for each patient. In month 2, ing in a turbulent recovery (Vaurio et al. 2006). a similar plan is followed but K/Na measured 2 days before the antici- pated interval is met and then at 48 hrs to fine tune the interval. By the Appropriate use of analgesic drugs in the preemptive and intraoperative third month you should expect the interval to now be predictable and it is period will decrease the amount of pain that the patient experiences in unusual to check electrolytes again unless clinically indicated. recovery (Lascelles et al. 1998), however, break through pain commonly occurs. We do advise clients to double the dose of prednisolone at times of patient stress to 0.25mg/kg/d every 12 hours at times of stress. This Thus, regardless of the use of preemptive or intraoperative analgesia, pain includes events like boarding kennels, other illness, moving house, house should still be anticipated and all patients should be assessed for pain in full of visitors, the introduction of new pets or family members etc.. recovery. Survival times following bilateral adrenalectomy are good with an approxi- Fortunately, differentiation really isn’t necessary since excitement, regard- mate 10% mortality rate, comparable to unilateral procedures. Just as with less of the cause, is not appropriate in the recovery period. unilateral adrenalectomy, prognosis appears independent to histopatholo- gy of the mass, including whether benign or malignant. With a well regulat- Excitement with subsequent physiologic stress in the recovery period ed patient after surgery, it should be not be expected that the patient dies can lead to respiratory and hemodynamic crisis, thus, all forms of stress from an Addisonian-related complication. should be treated (Manworren et al. 2004; Pandharipande et al. 2005). Drugs that provide both sedation AND analgesia should be utilized. Options in this category include opioids and alpha-2 agonists. Opioids are generally first choice therapy because of their analgesic potency. Give opioid bolus IV Full to ½ dose of original opioid Hydromorphone, morphine, methadone, butorphanol, etc…. Buprenorphine is slow so use it with an alpha-2 if recovery is really bad If opioid therapy is already appropriate or the patient is really frantic, 211

13–15 NOVEMBER, 2021 administer an alpha-2 agonist 0140 Provides sedation, enhance analgesia provided by opioids and decreases HOW I TREAT GENETIC DISEASE BEFORE ONSET the anesthesia-induced stress response. J. Bell Alpha-2 agonists are often used in human medicine to control excitement and pain following recovery from anesthesia. (Pandharipande et al. 2005). Enfield/United States of America ‘Micro’ dose = 1-5 microg/kg Qualifications: IV if you can – it works faster Jerold S Bell, DVM Quick tip: ‘Hub’ for small dog, 0.1 mls for medium dog or cat, 0.2 for large Adjunct Professor of Clinical Genetics dog, 0.3 for giant dog jerold.bell@tufts.edu Don’t worry if you use a larger dose – the patient needs sedation! The hallmarks of hereditary disease are its pre-programed liability and the possibility to identify disease risk prior to clinical onset. Therefore, the If pain persists after initial treatment, other analgesic protocols that can role of the veterinarian is early identification of genetic risk and interven- be utilized include local anesthetic blockade and constant rate infusions. tion to prevent or mitigate the expression of genetic disease. What if the problem is opioid-induced dysphoria There are well documented, breed-specific hereditary diseases that occur in purebred dogs and pedigreed cats. For some of these diseases there Are you SURE? are genetic tests that can be run to determine disease predisposition. The WSAVA Canine and Feline Hereditary Disease (DNA) Test website, hosted RARE in private practice, academicians talk about it a lot at meetings by the University of Pennsylvania contains information on all DNA tests because opioids are used aggressively in academia, not as aggressively in available in dogs and cats. You can search by breed, disease, or laborato- most private practices ry. It contains links to the original published article on each disease test, as well as which laboratories run the tests: (http://research.vet.upenn. First choice: Sedate with an alpha-2 agonist or acepromazine and leave edu/WSAVA-LabSearch). This site lists all identified mutations, including the opioid alone if the patient is really painful rare mutations that may not be present in pet populations. Second choice (or first if patient isn’t very painful): Titrate butorphanol IV The International Partnership for Dogs - Harmonization of Genetic Testing up to 0.2 mg/kg website lists testable canine disorders and provides test relevancy ratings for individual breeds: https://dogwellnet.com/ctp/. Common genetic Third choice: Reverse with naloxone (titrate 0.01- 0.04 mg/kg IV – can disorders and tests for cat breeds can be found on the International Cat also administer IM) Care website: (https://icatcare.org/advice/cat-breeds). For choices 2 and 3: Be sure to add analgesia: Local blocks, NSAIDs, Some organizations list important testable disorders for each breed. eEtc… These can alert practitioners to the disorders that might more commonly be present in a breed. An example is the OFA-Canine Health Information In addition to the measures listed above, or instead of the measures listed Center website: http://www.ofa.org/breedtests.html. above depending on the patient: Screening for Hereditary Predisposition Treat for nausea/vomiting Certain breeds should undergo genetic testing early in life if evidence Ensure that the patient’s bladder is empty of parental DNA testing is not documented. For example, patients from breeds with an incidence of von Willebrand’s disease should be tested Check for hypoglycemia (more likely to cause long recoveries but can so that measures can be taken to prevent excessive hemorrhage during cause what looks like delirium) surgery or injury. Herding-type dogs with Collie lineage at risk of carrying the mdr-1 mutation should be tested before drug treatment. Boxers should Check electrolytes be tested while young for the dominant arrhythmogenic right ventricular cardiomyopathy (ARVC) gene. Carriers can be monitored for arrhythmias Administer anxiolytics through life, and when they occur can be put on antiarrhythmic drugs to prevent heart failure. We counsel owners of large-breed puppies to feed If the patient has cognitive decline, the patient may need added human lower calorie “large breed growth or puppy” foods to provide for a more attention (petting, etc.) uniform growth rate and better joint development. The expression of some genetic disorders cannot be altered. If a genetic test is available, it should be utilized pre-purchase so that owners are not burdened with predictable genetic disease. However, for owned animals it is a personal decision whether the owner wants to know if their pet has liability of developing a non-treatable genetic condition later in life. Some of these tests are for liability genes, and even an “affected” or “at risk” test result does not uniformly identify patients that will all develop the disease. Examples include polycystic kidney disease (PKD) in Persian, Himalayan and related cats, hypertrophic cardiomyopathy (HCM) in Maine Coon and Ragdoll cats, dilated cardiomyopathy (DCM) in Doberman Pinschers, and the (poorly penetrant) liability gene for degenerative my- 212 WSAVA GLOBAL COMMUNITY CONGRESS

elopathy (DM). For PKD and DM, these tests could also be used to rule out 0141 diagnoses in clinical patients with suspected genetic disease. HOW I TREAT DERMATOPHYTOSIS Dietary recommendations should be offered for identified genetic predis- positions such as; FUS/inflammatory cystitis in cats, dogs and cats with C. Noli non-struvite bladder stones, and obese “pre-diabetic” cats. Behavioral counseling and early training recommendations should be offered with CN/Italy breeds or individuals demonstrating aberrant or pathological behaviors. Qualifications: Gentle palpation for hip laxity should be performed on all puppy visits and on all dog spays and neuters while under anesthesia. The amount of laxity Chiara Noli or positive Ortolani motion should be noted in the patient record. Hip laxity does not guarantee future development of hip dysplasia, but most DVM, Dip ECVD will develop arthritis later in life. If a dog later presents with hind limb lameness, the notation of hip laxity under anesthesia may be informative. info@dermatologiaveterinaria.it If there is significant laxity identified in a young dog, pre-emptive surgery Introduction (triple pelvic osteotomy or juvenile pubic symphysiodesis) could be indi- cated. For dogs with hip laxity, weight control is an important method of In an animal with a normal immune system dermatophytosis is a self-lim- mitigating the severity and progression of arthritic changes. iting disease that resolves within a period of months to years, however all cases should be treated. Dermatophytes are not part of the normal skin Palpation for patella laxity when present is predictive of progressive dis- flora. Especially in the case of M. Canis, spread to other animals, contami- ease over time, and the same recommendations for weight control should nation of the environment and contagion to humans are significant issues. be offered. As opposed to hip dysplasia, patella laxity is not usually M. Canis is a significant zoonosis, particularly dangerous to children and present in young animals. The hereditary predisposition to patella luxation immunosuppressed individuals. Over 50% of persons exposed to infected may first become evident after an acute episode. Liability for ACL rupture cats will develop dermatophytosis and 15% of human dermatophyte infec- is also hereditary, but no predisposing clinical signs or genetic tests are tions are of animal origin. currently available (except for the risk of dogs to rupture their opposite ACL after rupturing the first one). Contrary to past opinions, systemic therapy is always required even in the case of localized disease. Fungi can be isolated from “normal” skin locat- The predisposition for hereditary disease is lifelong, so most hereditary ed well away from an obvious lesion and systemic therapy results in more diseases must utilize lifelong control and monitoring. Hereditary diseases rapid cure. Topical therapy reduces the number of spores and hyphae on should not be treated as episodic disease, as owners will quickly become the skin. These fungal elements are not exposed to circulating systemic dissatisfied with repeated treatments for the same presentation. These antifungal agents until the drug has been incorporated into new keratin. include allergies (chronic ear infections, seasonal pruritis, hot spots), Topical therapy reduces environmental contamination and contagion, non-struvite bladder stones, feline inflammatory bladder disease/FUS, and shortens the duration of systemic therapy and reduces the risk of relapse. chronic gastroenteritis. The usual therapeutic protocol is systemic therapy combined with 1-2 times a week shampooing or soaking with a topical fungicide. The clinical presentation of hereditary disease can be preceded by recognizable clinical signs. The “red line” of marginal gingivitis in cats is a Topical therapy precursor to lymphoplasmacytic gingivostomatitis. Waiting for advanced dental disease to occur in these cats misses the opportunity to employ Prior to beginning treatment, clipping the coat is vital. The hair should diagnostics or therapeutics to mitigate the progression of the disease. be clipped with a 2-3cm margin from localized lesions but in the case of generalized dermatophytosis or patients with a long coat the whole animal Biomarkers are becoming more readily available to diagnose and differ- should be clipped. The clipping may need to be repeated monthly. Clipping entiate hereditary from non-hereditary presentations. These are available should be done carefully as trauma to the epidermis provides a portal of for inflammatory GI disease, cardiac disease, and early identification of entry for dermatophytes. cancer. Topical treatment should be applied 1-2 times weekly until cured. The more effective topical treatments include the azole derivatives (mi- conazole, ketoconazole, econazole and enilconazole) and lime sulfur. Recent evidence casts doubt on the effectiveness of chlorhexidine in der- matophytosis. Enilconazole is highly effective and has resulted in negative fungal cultures after only two applications but is only registered for use in dogs and horses. Enilconazole has been extensively used in cats but adverse reactions, including death, have been reported after even a single application. Commercial shampoos containing econazole or miconazole are now registered for cats and are to be preferred over medications for humans. Chlorhexidine foams and shampoos are useful if at high per- centage (over 2%). Povidone iodine is irritant and stains the coat. Creams are generally of reduced value as they are licked off. Creams or lotions are useful in animals too young for systemic therapy. In-contact animals should be considered infected and treated at least with topical therapy. Systemic therapy Griseofulvin is still widely used in veterinary medicine and will cure nearly all cases of M. Canis and many cases of T. mentagrophytes. Griseofulvin acts on the microtubules of the fungal cell inhibiting mitosis and hence, is fungistatic rather than fungicidal and is effective only against actively 213

13–15 NOVEMBER, 2021 dividing fungal cells. The clearance of the fungus relies on an exfoliation es. There is no evidence of teratogenic side effects but there have been of the infected keratin and hair and an effective immune system. Prior to no studies to confirm the safe use of itraconazole in pregnancy. therapy, cats should be checked for FIV and FeLV. Terbinafine is fungicidal with actions against the fungal cell wall and Absorption of griseofulvin is enhanced by being given with a fatty meal. membrane. Normal dose rates quoted are between 10-20mg/kg daily but Ultramicrosized forms of griseofulvin are better absorbed at can be used dose rates of 30-40mg/kg day have produced faster cure rates in a study at a lower dose. In man, griseofulvin enters the stratum corneum by with cats. The drug accumulates in sebum, keratinocytes and hair follicles passive diffusion and active secretion by the apocrine glands, remaining and maintains therapeutic levels for up to 2-3 weeks after administration. there for 36-72 hours after administration. Because of this short duration Terbinafine is indicated in cases of resistant M. canis infections or in of action and its fungistatic action, griseofulvin should be given daily cases of onychomycosis where traditional therapy required 6-12 months for at least 6 weeks. Treatment should be continued at least until the of treatment. Terbinafine has poor activity against yeasts. Liver enzyme lesions have resolved and preferably confirmed by a negative culture. The elevation can occur but the drug is regarded as safe and highly effective. standard dose for cats is 40-50 mg/kg/day and dogs 50-100mg/kg/day. No studies have indicated that terbinafine is superior to itraconazole. The use of the ultramicrosized form allows a reduction to 1/3 of these dose rates. Monitoring therapy The drug may produce gastrointestinal side effects, in which case, the Standard treatment is systemic treatment for at least eight weeks com- clinician may wish to switch to an alternative drug. Lethal bone mar- bined with once or twice a week topical therapy. After three weeks, the row suppression can occur in cats especially Siamese, Himalayan and topical therapy can be suspended. On the fourth week, perform a fungal Abyssinian breeds and cats positive to FIV and FeLV. Alternative drugs culture from material collected using the McKenzie toothbrush technique. (itraconazole) should be considered in these breeds and individuals. Cats While awaiting the results, the systemic therapy should be continued. receiving griseofulvin should be have their hematological parameters Should the culture be negative then treatment can be suspended. If posi- monitored monthly. Delayed toxic reactions, with systemic signs, weeks tive, treatment should continue for a further four weeks and then a further after therapy has been stopped have been reported. Griseofulvin is highly culture taken. teratogenic and must not be used in breeding animals. Griseofulvin should not be given before six weeks of age. Environmental decontamination Ketoconazole is a fungistatic imadazole that inhibits ergosterol synthesis Spores remain viable in the environment for up to 18 months but the most in the fungal and yeast cell membrane. Ketoconazole is better absorbed important contaminant is pieces of infected hair. It is essential to decon- with acidic food such as tomato juice. Skin levels are maintained for at taminate the environment of the patient, limit the area in which the animal least 10 days after administration and thus ketoconazole can be given for has access and to minimize contact with other animals and persons. a shorter period than griseofulvin. The standard dose for cats is 5mg/kg BID and 5-10mg/kg BID for dogs and maintained for at least 30 days. Disinfectants showing the best results are either 1:10 solutions of com- mon bleach (diluted to 0.05 - 0.5% sodium hypochlorite) or enilconazole Up to 50% of strains of M. canis are resistant to ketoconazole and the spray (marketed for Aspergillus control in poultry houses). Chlorhexidine drug offers no advantages over griseofulvin for routine use. Ketoconazole alone is ineffective as an environmental decontaminant. Curtains and has a role in dogs that fail to tolerate griseofulvin or in cases of resistant carpets can be vacuumed then steam cleaned with added disinfectant. All Trichophyton infection. surfaces should be cleaned twice weekly with a disinfectant solution and any combs or other objects in contact with an infected animal should be In cats, and sometimes in dogs at high dose rates, the drug causes soaked for at least 10 minutes in a bleach solution. elevations in liver enzymes and occasional hepatotoxicity. Ketoconazole inhibits steroid hormone synthesis, resulting in adrenal suppression and lowered testosterone levels. Gastrointestinal side effects also occur. Ketoconazole should not be used in pregnant animals or patients under six weeks of age. Itraconazole has an action similar to ketoconazole, being more effective and less toxic. Itraconazole accumulates in the skin and levels in the sebaceous glands may be ten times that of plasma. Therapeutic levels persist in the epidermis for 2-4 weeks after administration. Itraconazole is best absorbed with food and given at a dose of 5-10mg/kg daily. The drug is available in 100mg capsules and, in some countries, as a 10mg/ ml solution. The capsules may be opened, mixed with butter and stored in the refrigerator to dose smaller patients. Because of its accumulation and persistence in skin, itraconazole can be used on an alternate week sched- ule (1 week on, 1 week off) for a total of 6-8 weeks. Itraconazole is the drug of choice for pseudomycetoma of the Persian cat. The granulomas may be so well encapsulated that the drug fails to penetrate effectively. In such cases, itraconazole should be given until the nodules have shrunk to a size suitable for surgical resection and then continued for at least 4-6 weeks post surgery. Gastrointestinal side effects occur with itraconazole together with mild elevations in liver enzymes. A slight rise in ALT indicates good absorption but levels above 200IU/l suggest the dose should be lowered or therapy suspended. A lack of any rise in ALT indicates that the drug is being given at too low a dose or not on a full stomach. An idiopathic vasculitis, with deep crater like ulcers, has been reported in dogs on prolonged high dos- 214 WSAVA GLOBAL COMMUNITY CONGRESS

0142 Occasionally, these teeth can become infected through the dentinal tu- bules. Again, this infection will go undiagnosed without dental radiology. HOW I TREAT FRACTURED TEETH However, teeth with no to small pulpal exposures tend to be the ones with clinical abscessation. B. Niemiec First, perform a thorough visual exam to determine pulp exposure or other San Diego/United States of America extensive damage. Next, use a dental explorer or small endodontic file to definitively rule out pulp exposure (any soft spot should be a suspect). Qualifications: Finally, expose a dental radiograph to rule out endodontic disease. Brook A. Niemiec DVM If the dental radiographs are within normal limits, perform a bonded sealant (see below) and recheck radiographs in 9-12 months to ensure Diplomate, American Veterinary Dental College continued vitality. Diplomate, European Veterinary Dental College If there is radiographic evidence of endodontic disease root canal therapy or extraction is indicated. Fellow, Academy of Veterinary Dentistry Tooth Anatomy: Complicated crown fractures: Teeth are roughly broken up into three layers: enamel, dentin, and pulp. Broken teeth are a very common problem in animal patients. As a matter of fact, 1 out of 10 dogs has a broken tooth in their mouth with direct root The innermost layer is the endodontic system (root canal or pulp). It canal (nerve) exposure, which is called a complicated crown fracture. contains the nerves, blood vessels, and connective tissue which supply While it may seem obvious that an exposed nerve hurts or a diseased and nourish the tooth during life. The blood and nervous supply enters the tooth would be a source of infection, this knowledge is not universal. It is tooth through the very bottom or apex of the root. a common misconception amongst clients and general practice veterinari- ans that this doesn’t hurt by the fact that the pet is eating just fine. In fact, The outer layer of the tooth crown is enamel, which is an inorganic many clients are told by their veterinarians to “watch it” or “it doesn’t both- substance. It is virtually all (97%) calcium and phosphorus and is the er him, wait until it abscesses”. The fact is, once the nerve is exposed, the hardest substance in the body. Enamel has no nervous or circulatory tooth cannot heal itself and therefore requires therapy. system. It is applied in a very thin layer (less than 1 mm thick in veterinary patients) over the tooth surface during development by a cell layer called Direct pulp exposure is initially excruciatingly painful for the pet. If it is amelioblasts. Once eruption has occurred, enamel cannot be replaced or not treated, the exposure will invariably result in pulp death, necrosis, and repaired. subsequent infection. The central layer, which is the vast majority of the tooth structure in Fractured and/or infected teeth do affect animals by creating pain, mature patients, is dentin. Dentin has roughly the same mineral content as infection, and even fatigue, but often these signs are subtle or hidden. In bone. Dentin is a somewhat living structure which has a nervous supply addition, signs of infection generally present gradually, and are therefore and can occur can respond to stresses. Running at right angles to the root less noticeable. However, most owners see a notable or even dramatic canal all the way around the tooth from the root canal out to the enamel improvement in their pet’s attitude and energy level after therapy is are dentinal tubules. Each one of these dentinal tubules contains an provided. Because animal patients are typically much more stoic than odontoblastic process, which is basically a nervous supply; however they humans, a lack of obvious signs of oral pain should not be misinterpreted are only sensory and can only report changes as pain. There are approxi- as a benign state. It is typical for animals to continue to eat normally mately 50,000 dentinal tubules per mm2 coronal dentin. Therefore, a 1 cm despite intense oral pain. Furthermore, after a broken tooth eventually area of enamel loss will expose 3-4 million odontoblasts! dies and much of the associated pain subsides, the root canal system acts as a bacterial pathway, creating not only a local infection, but also Response to Damage: allowing bacteria to spread systemically into the bloodstream. Bacteria in the bloodstream can negatively affect numerous vital organs including the Exposure of the dentinal tubules will lead to much quicker dentinal fluid heart, liver, kidney, lungs and brain, leading to serious systemic disorders. flow out through these dentinal tubules via the capillary effect. This increase in fluid flow deforms the A-delta C-delta fibers and thus will be All teeth with direct pulp/nerve exposure must be treated; ignoring these perceived by the patient as pain. Anything that will change the flow rate teeth is NOT an option. will cause the nerves to fire and result in pain (sensitivity). This includes heat, cold, and desiccation. The sensitivity is actually a sign of low grade Treatment: pulp inflammation known as pulpitis. These fractures are exceedingly common in large breed dogs. However, they rarely show clinical signs and The treatment options for these teeth are vital pulp therapy, root canal therefore are only diagnosed with a careful oral exam, often under general therapy, or extraction. When properly performed, root canal or extraction anesthesia. Therefore, this commonly goes undiagnosed and therefore should result in complete and lifelong resolution of pain and/or infection. untreated. There are advantages and disadvantages to each treatment option, and recommendations vary depending on which tooth is involved and the level In addition to the sensitivity produced by the exposure of the dentinal of disease. We will discuss these treatment options and where indicated. tubules, there is a possibility of ingress of bacteria into the root canal system. In some cases this can result in endodontic infection and subse- Vital pulp therapy quent abscessation. This occasionally can be seen clinically as a swelling or draining tract, but is generally subclinical and therefore undiagnosed. Vital pulp therapy (or pulp capping) is designed to keep the tooth alive by The only way to diagnose this infection is via dental radiographs. medicating and protecting it from the oral environment. This procedure in- volves sterilely removing a small part of the coronal root canal (about 5-7 Uncomplicated Crown Fractures mm). After haemorrhage is controlled; a protective product called mineral trioxide aggregate is placed directly on the pulp. On top of this, a layer These are very common in large breed dogs. They occur when a piece of glass ionomer restorative is placed on top of the MTA and light cured. of the crown is broken off, which exposes the dentin but not the pulp. 215

13–15 NOVEMBER, 2021 This product bonds chemically to the dentin and gives and excellent bac- 0143 terial seal. However, this is not a super strong restorative, and therefore, the final restoration is composite resin. FELINE HEALTHY AGING When performed within 48 hours this has an OK prognosis, but is still N. Dowgray far less than standard root canal therapy. After 48 hours the prognosis becomes poor. For this reason, we do not use this procedure on mature Tisbury/United Kingdom teeth. However, for immature teeth it will keep the patient comfortable and the tooth alive long enough to accept root canal therapy. (See below) Qualifications: Note, this must be performed properly and immediately to have a chance of success. Even under ideal conditions, vital pulp therapy carries a lower Nathalie Dowgray prognosis than standard root canal therapy. BVSc, MRCVS, PGDip, PhD Root Canal Therapy Introduction to ageing Briefly described, root canal therapy involves removal of the nerve and as- sociated structures, disinfection and filling of the canal, and restoration of Ageing is the process of growing older and healthy ageing is the process the surface of the tooth. When properly performed, this has an EXCELLNT of growing older in the absence of age related disease. In UK cats the long term prognosis and maintains the structure and function of the tooth. current life expectancy is around 14 years but cats have the potential to Further, this procedure is far less painful and has fewer complications live up to 30 years, so to expend the healthy life-span of a cat the goal is than extraction, especially in regards to major (canine and carnassial) to delay or prevent the development of age related diseases and to slow teeth. The lower canine teeth are specifically associated with jaw strength, the progress of any age-related conditions that occur. which makes it optimal to avoid extraction of these teeth if possible. Although almost any tooth may be treated with root canal therapy, it is There are a number of biological processes that are considered hall marks especially recommended for treating larger, strategic teeth. of ageing; genomic instability, telomer attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunc- Extraction tion, cellular senescence, stem cell exhaustion and altered intracellular communication. To be considered a hall mark of ageing the process must This involves complete removal of the tooth and its root(s). This is an be potently reversable and through being reversed the signs of ageing are important point, as only complete extraction will resolve the infection and also reversed. Caloric restriction protocols have been shown in many spe- retained roots are a very common complication with extractions. This is cies to improve nutrient sensing pathways, protein formation, autophagy a good choice for small teeth, but large teeth should be saved. The ad- and insulin sensitivity as well as reducing genomic instability, telomere vantages of extraction include decreased surgical time and expense (for shortening and oxidative damage to mitochondria. Exercise protocols smaller teeth), and this treatment option requires no long term follow-up. have been also shown to reduce mitochondrial dysfunction and improve muscle mass and insulin sensitivity. Both diet and exercise have been Conclusions: shown to reduce chronic inflammatory states that occur as the result of altered intracellular communication. There is currently a lot of interest in Fractured teeth are a very common condition in small animal veterinary ‘Nutraceuticals’ that activate some of these biological pathways without patients. Therefore, a complete (as possible) conscious oral exam should the hard work. be performed on every patient and a thorough oral exam and radiographs completed during every dental procedure. Finally, all fractured teeth with What can we do in the cat? direct pulp exposure must be treated. Ideally, this would be root canal therapy (especially with strategic/large teeth), but complete extraction is The majority of age related diseases in the cat start to increase in prev- also an acceptable means of therapy. In immature pets, vital pulp therapy alence from 8-10 years of age but the biological processes that lead to can be performed to allow the tooth to mature for future root canal the physical appearance of ageing and the development of these disease therapy. are starting to occur from around 7 years of age. Regular examinations of cats from 7 years of age to prevent conditions such as obesity developing Suggested readings: and to diagnosis diseases such as hypertension, hyperthyroidism or renal disease earlier in the process to prevent or slow down disease progres- Restorative dentistry for the general practitioner. Practical Veterinary sion so extend the healthspan if not the lifespan of the cat. Publishing, San Diego CA The Feline Healthy Ageing Clinic Dupont G: Pathologies of the Dental Hard Tissues In: Small Animal Dental, Oral and Maxillofacial Disease--A Color Handbook, Manson Publishing Ltd, The Feline Healthy Ageing Clinic (FHAC) recruited and examined cats for London 2010 the first cohort between February 2017 and March 2020. Cats aged 7-10 years living in the North West of the UK were invited to attend the clinic. Cats were assessed every 6 months in a combination of veterinary and veterinary nurse lead clinical examinations. These included weighing, measuring blood pressure, recording body condition score and a dental assessment. Veterinary lead examination also included an orthopaedic examination and the collection of blood and urine samples. Two hundred and size cats were enrolled in this 1st cohort, median age 8Y (IQR 7-9). On their enrolment examination, 29% of the cats had a heart murmur, 5% had BP>160mmHg, 54% had dental disease and 58% had findings on their orthopaedic examination suspicious of musculoskeletal disease. 10 cats had increased liver enzyme concentrations, 19 cats had potential kidney disease and 6 cats were hyperthyroid. Only 12% of cats 216 WSAVA GLOBAL COMMUNITY CONGRESS

had abnormalities found following complete screening. 0145 CASE STUDIES IN FELINE MEDICINE S. Taylor, N. Dowgray Tisbury/United Kingdom Qualifications: Samantha Taylor BVetMed(Hons) CertSAM DipECVIM-CA MANZCVS FRCVS sam.taylor@icatcare.org Nathalie Dowgray BVSc, MRCVS, MANZCVS (feline), PGDip IAWEL, PhD Nathalie.dowgray@icatcare.org Case studies in feline medicine In this talk, Nathalie Dowgray, head of ISFM, and Samantha Taylor, feline specialist, present a series of case studies from Nat’s Feline Healthy Ageing Clinic and Sam’s work in referral medicine. In all cases we discuss Cat Friendly Clinic approaches and what we learnt from the cases. 217

13–15 NOVEMBER, 2021 0146 they truly can become pets to their owners and most koi pond keepers are willing to invest in veterinary care for their fish to help them live long lives, THE ABC’S OF KOI PRACTICE - GETTING STARTED 60 years or more! N. Saint-Erne Glendale/United States of America Qualifications: Nicholas Saint-Erne, DVM Certified Aquatic Veterinarian nsainterne@gmail.com THE ABCs OF KOI PRACTICE - GETTING STARTED Nick Saint-Erne, DVM, CertAqV nsainterne@gmail.com Phoenix, Arizona USA Introduction Koi is the common name given to an ornamental carp that was produced by selective breeding from the Amur carp (Cyprinus rubrofuscus). The original Japanese name for this fish is Nishikigoi, which means “brocaded carp.” The carp were originally bred in ponds for food, but natural color mutations stimulated an interest in producing a prettier fish that was kept for aesthetic pleasure. Now, koi are one of the most commonly kept orna- mental fish, and also among the most expensive, with some show winning koi selling for over a million dollars! Objectives To teach basic health care for koi patients seen by veterinarians. Aquatic Veterinary Medicine is a rapidly growing field and Veterinarians around the world are involved in the production of food fish species as well as orna- mental fish for ponds and aquariums. Among the ornamental fish species, koi are very often treated by veterinarians because of their beauty, large size (up to a meter in length), long lifespan (60 years or more), and value (koi can be sold for hundreds of dollars each, up to thousands and tens of thousands of dollars for fancier varieties). Koi pond owners are very likely to seek veterinary care for their fish when problems arise. A Assess: Examine the fish, the pond or aquarium, the water quality to assess the conditions in which the fish is kept. Many health issues initially are related to poor water quality, inefficient filtration, improper diet, or overcrowding. B Biopsy: perform skin mucus scrape with direct smear microscopic ex- amination, along with a wet mount examination of a fin and gill biopsies. These tests will help determine if protozoa, flukes, crustacean parasites are present, and sometimes will reveal bacterial and fungal problems. C Care: provide the correct treatment protocol based on the findings from the biopsies and other diagnostic tests performed. Often, the primary concern will be water quality or filtration capacity, and these need to be corrected as well as adding any therapeutic drugs for treating the fish. Conclusion Learning the basics of koi care will help veterinarians better assess, diagnose and care for their patients. As koi are long lived and large fish, 218 WSAVA GLOBAL COMMUNITY CONGRESS

0147 0148 FEED, FEEDING BEHAVIOR AND BODY CONDITION WHICH ANCYLOSTOMA SPECIES IS WHERE IN THE DOMESTIC CATS OF THE WORLD J. Tepper D. Bowman Manorville/United States of America Ithaca/United States of America Qualifications: Qualifications: Dwight D. Bowman, MS, PhD Julius M. Tepper, DVM, CertAqV Professor of Parasitology cypcarpio@aol.com A review of koi food and feeding behavior is important to treating clinical ddb3@cornell.edu issues seen in koi practice. Although obesity is occasionally encountered, especially in individuals of certain varieties of koi, the majority of cases in- Introduction volve low body weight. This may involve only one or several individuals or In recent publications it has been stated that the common hookworm all the koi in the pond. Examples of individuals displaying abnormal body parasite present in cats in Thailand and parts of China is the canine hook- condition will be given. An overview of typical koi food and feeding prac- worm, Ancylostoma caninum. tices will help to guide the practitioner in correcting these issues. Feeding behavior can also be reviewed in an effort to understand abnormalities. Objectives In koi, 3 distinct actions can be observed during normal feeding behavior: This talk will examine the different publications and examine the differ- anticipation, intake and chewing/ swallowing. Examples of conditions ences between the more common species found in cats, Ancylostoma associated with disturbances to normal feeding behavior will be given. tubaeforme, Ancylostoma braziliense, and Ancylostoma ceylanicum and how they differ in morphology and pathogenesis both tin cats and as zoonotic agents. Methods The discussion will focus on means of telling the different forms apart and the molecular methods that can be used to distinguish the different species. Results The hope is to begin a discussion as to what species are present where and to initiate more research to categorize the specific forms that are found in different parts of the world. Conclusions All the infections in cats are probably treated in the same fashion, but it is important to note that some of these parasites are more important zoonotic agents than others. 219

13–15 NOVEMBER, 2021 0149 0150 THREE WORLD-TRAVELERS – FELICOLA CARDIOVASCULAR PHYSICAL EXAMINATION SUBROSTRATUS, LYNXACARUS RADOVSKYI AND NOTOEDRES CATI E. Durham D. Bowman Bonita Springs/United States of America Ithaca/United States of America Qualifications: Qualifications: Dwight D Bowman H. Edward Durham Jr. MS, PhD Professor of Parasitology CVT, LATG, VTS (Cardiology) Introduction PhoenixVTS@outlook.com There is a louse and two mites that have travelled the world on the domes- A complete and thorough physical examination is critical to every veteri- tic cat. nary patient. Objectives Observe the patient when they are relaxed and breathing normally if This talk will examine the world distribution of these parasites and show possible. Note any coughing, muscle wasting, or abdominal distention. that the cat has successfully helped these parasites move between conti- Record the rate, depth, and effort of respiration. The normal respiratory nents and islands. rate in small animals is ~ 18 - 30 breaths/minute. Tachypnea = increased respiratory rate. Dyspnea = distressed and labored breathing Methods The work will present the geographic range of the parasites, how they Inspiratory dyspnea is characterized by a prolonged, labored inspiratory differ from various “local” species, and how they have in some cases effort, and a quicker, easier expiratory phase. Inspiratory dyspnea usually supplanted the native species. indicates an upper airway disorder. Results Orthopnea is a term applied to respiratory distress exacerbated by recum- These parasites have appeared now from the far north to tropical islands. bency. Animals showing orthopnea assume a standing or sitting position with elbows abducted and neck extended. Conclusions When known, diagnosis and treatment will be considered and discussed. Mucous membranes allow you to assess hydration, cardiac output, and oxygenation. Normal mucous membranes are pink and moist, with a cap- illary refill time of < 2 seconds. Pale mucous membranes may indicate de- creased cardiac output, anemia, or peripheral vasoconstriction. Peripheral vasoconstriction occurs with hypothermia and shock. Cyanotic mucous membranes (blue-colored) indicate an increase in the concentration of deoxygenated hemoglobin. Persistent jugular distention is an important indicator of right heart fail- ure. And is commonly seen with pericardial effusion, but also occurs with other causes of right-sided congestive heart failure (e.g., dilated cardio- myopathy). A jugular pulse that extends more than about one third of the way up the neck usually indicates tricuspid regurgitation. Thoracic palpation of the precordial impulse allows you to assess the strength and location of the apex beat. The apex beat is the point on the chest where you feel the heart beating the strongest against your hand. The apex beat is sometimes incorrectly called the point of maximal inten- sity (PMI), which is a term to describe the location of a murmur. A thrill is a vibration felt over the heart and it is associated with turbulent blood flow from a murmur. During cardiac auscultation the animal should be standing during aus- cultation to maintain the normal anatomic position of the heart. All valve areas MUST be ausculted. Begin your cardiac auscultation at the apex beat. The apex beat is a convenient “landmark” for the mitral valve area of auscultation in normal animals. The aortic valve area of auscultation is located one intercostal space further cranially (i.e., left fourth intercostal space) just above the costochondral junction. The pulmonic valve area of auscultation is usually located one intercostal space further cranially (i.e., left third intercostal space) just above the sternum. The tricuspid valve area is located on the right side at about the level of the costochon- dral junction between the third to fifth intercostal spaces. This is usually directly across from the apex beat on the left. One should also auscultate the left hemithorax high in the axilla (about the second intercostal space). This location is where the continuous murmur of a patent ductus arterio- sus (PDA) is best heard. 220 WSAVA GLOBAL COMMUNITY CONGRESS

The first heart sound (S1) is produced by vibrations of the heart at the Innocent murmurs are heard in puppies and kittens as soft systolic beginning of contraction and is associated with closure of the atrioven- murmurs heard best at the mitral or aortic valves. Physiological murmurs tricular (mitral and tricuspid) valves. S1 is loudest over the mitral valve are common in animals that are anemic and occur as a result of changes area, and is louder, longer, and lower pitched than the second heart sound in blood viscosity (which results in disruption of normal laminar blood (S2). S2 is produced by vibrations of the heart at the end of systole and flow). Pathologic murmurs are secondary to valve abnormalities or septal is associated with closure of the semilunar (pulmonic and aortic) valves. defects. Often, it is not possible to distinguish physiologic from patho- S2 is heard loudest by moving the stethoscope cranially to the left heart logic murmurs on physical examination, and additional diagnostics are base. S2 is shorter and higher pitched than S1. needed. The loudness of a murmur does NOT necessarily correlate with the seriousness of the defect. In dogs and cats, it is always abnormal to hear the third and fourth heart sounds :S3 and S4. If you have a gallop in a small animal, there is cardiac A systolic click is an extra heart sound that is occasionally heard between pathology.Muffled heart sounds may indicate the presence of pericardial S1 and S2. They are usually mid to late systolic sounds, relatively high or pleural effusion. It can also occur in animals that are overweight or pitched, and labile. They are thought to be due to buckling of the mitral have intrathoracic masses. or tricuspid valves in early degenerative valve disease. Clicks are most common in small breed, older dogs. Heart rate should be counted to identify bradycardia or tachycardia. There are two normal rhythm variations in the dog. Normal sinus rhythm The animal should be standing and relaxed when you perform ausculta- has regular beat with a normal rate. A sinus arrhythmia has a normal to tion of the respiratory system and they should not be panting. If neces- slow heart rate which is characterized by cyclic increase and decrease in sary, the animal’s mouth must be gently held shut during auscultation. The heart rate. This is sometimes specifically associated with respiration, and entire thorax should be systematically ausculted. Normal breathing should results in an increase in heart rate during inspiration and a decrease in be almost silent. heart rate with expiration. Crackles (which are frequently classified as coarse or fine) are discon- Common rate and rhythm abnormalities include beats that occur pre- tinuous sounds usually heard during inspiration. Crackles are caused by maturely, and that are associated with pulse deficits. These are termed various pulmonary disorders (e.g., chronic bronchitis, pulmonary edema) extrasystoles (e.g., atrial and ventricular premature complexes). Bursts in which some of the smaller airways are collapsed during the early phase or runs of extrasystoles are termed paroxysmal tachyarrhythmias (e.g., of inspiration, then suddenly open with a crackling sound as inspiration with paroxysmal atrial and ventricular tachycardia). A remarkably irregular progresses. Crackles with a low to normal heart rate suggests primary tachyarrhythmia is termed a chaotic tachyarrhythmia (e.g., as occurs with pulmonary disease (increased vagal tone). Crackles with an elevated heart atrial fibrillation). A persistent regular tachycardia (e.g., with a continuous rate suggests congestive heart failure (increased sympathetic tone). supraventricular or ventricular tachycardia) or a persistent regular brady- cardia (e.g., with complete AV block). Any abnormality in heart rate and/ Pulses are characterized in terms of rate, rhythm, and quality. At some or rhythm that is detected during auscultation is a clear, unambiguous point during auscultation, it is important to simultaneously palpate the indication to perform electrocardiography to determine the precise nature pulses. The femoral artery is usually the most convenient to locate. of the rate and/or rhythm abnormality. Pulses should be synchronous with cardiac auscultation. In a patient with a normal rhythm, the heart rate and pulse rate will be equal. Pulse deficits Characterization of heart murmurs is based on the timing during the cycle, indicate an arrhythmia is present. Assessment of pulse quality can be location or PMI of the murmur, and intensity (loudness) are the most very useful. Hyperkinetic pulses are excessively strong. These occur in important. states of increased cardiac output such as anemia, and with a left-to-right shunting PDA. Hypokinetic pulses are those that are weak. This occurs Timing and duration in the cycle: If the murmur occurs between S1 and S2, with poor cardiac output and subaortic stenosis. The term variable is used it is systolic (common in small animals). If it occurs between S2 of one to describe pulses that vary in strength (e.g., with atrial fibrillation). It is beat, and S1 of the following beat, it is diastolic (extremely uncommon important to remember that palpation of the pulse does not estimate the in small animals). Continuous murmurs (e.g., such as with left-to-right blood pressure, as you are palpating the difference in systolic to diastolic shunting patent ductus arteriosus) are heard throughout the cardiac cycle, pulse pressure. and peak in intensity at about the time of S2. The abdomen should be palpated for the presence of asites which can be Location and radiation: Location refers to the position of the stethoscope related to right ventricular heart failure. at which the murmur is heard the loudest. We frequently describe PMI as the valve area at which the murmur is heard loudest, e.g., “the murmur [ED1] is heard loudest at the mitral valve” or “at the pulmonic valve”. . Correct recognition of the PMI and pattern of radiation can be helpful in identify- ing the specific cardiac abnormality. Intensity: Grade 1/6: Softest murmur audible in a quiet room after minutes of listening Grade 2/6: Soft, readily heard, but focal over one valve only Grade 3/6: Prominent, easily heard, radiates to other areas Grade 4/6: Loud, radiates widely, without a palpable thrill Grade 5/6: Loud and accompanied by a palpable thrill Grade 6/6: Loud enough to be heard with the stethoscope held off the thorax Murmurs are also classified as innocent, physiological, or pathological. 221

13–15 NOVEMBER, 2021 0151 SNS stimulation tax the heart’s ability to function. Again, forward cardiac output is affected, yet any increases in RAAS and other mechanisms only NURSING OF THE CARDIAC PATIENT exacerbate the situation. As the vascular volume continues to be retained and cardiac output is decreased, the volume “back up” starts to increase E. Durham pressure in the heart chambers and vessels attached to it. Heart failure is often termed “right-sided” or “left-sided” referring to the ventricle that Bonita Springs/United States of America is primarily affected. Generally, when someone uses the term congestive heart failure (CHF) or just heart failure; they are referring to failure of Qualifications: the LV, back-up of pressure in the LA, and the development of pulmonary edema. If the pressure in the LA exceeds ~ 24 mmHg, then fluid will H. Edward Durham Jr. transude into the pulmonary interstitium and alveoli. (1) Most will specify “right heart failure” when referring to failure of the RV, pressure and fluid CVT, LATG, VTS (Cardiology) back-up in the abdominal organs and/or ascites. It should be noted that both may occur in a single patient, either in series or simultaneously. You PhoenixVTS@outlook.com may also hear the term, “biventricular failure” meaning both the right and The most logical beginning point is understanding the anatomy, and left ventricles are affected, and both ascites and pulmonary edema can physiology of the heart. In Normal circulation deoxygenated blood returns develop. to the right atrium (RA, pressure ~3-7 mmHg) from the venous system culminating with the cranial and caudal vena cave, which enter the RA. Heart failure in dogs has several causes. Chronic Myxomatous Valvular This blood then passes through the tricuspid valve (TV) from the RA, and Degeneration (CMVD), is common in smaller breed dogs but may be seen into the right ventricle (RV, pressure ~25/0 mmHg) during ventricular in any breed, especially the geriatric. With this heart disease, the connec- diastole. During systole, the RV forces the TV closed, and blood past the tive tissue layers of the heart valves begin to degenerate and become pulmonary valve (PV) into the main pulmonary artery (pressure ~25/10 unable to completely occlude blood flow during systole. Most often occur- mmHg). This is when the S1 heart sound occurs. The Main PA bifurcates ring on the mitral valve, it allows excess pressure and volume to move into into right and left pulmonary branches, then divides further to create the the LA. The LA will dilate to attempt to keep pulmonary venous pressures pulmonary arterial system. These smallest pulmonary capillaries carry normal. Eventually, the patient will decompensate due to the activity of this deoxygenated blood past the alveoli, allowing for the gas transfer of RAAS, and the pressure and volume load increases in the pulmonary carbon dioxide (CO2) out, and oxygen (O2) into the bloodstream. After venous system will lead to pulmonary edema. Dilated Cardiomyopathy passing by the alveoli, blood is said to be in the pulmonary venous sys- (DCM) is more often presented in mid-sized to large breed dogs, although tem. This O2 rich blood moves through the progressively increasing sized exceptions do occur. Dilated Cardiomyopathy is a disease of the heart pulmonary veins until finally reaching the four main pulmonary veins (PV) muscle, the myocardium. The hallmark of DCM is poor contractility, and a which empty into the left atrium (LA, pressure ~7-10 mmHg). At the end of large LV and LA. Since the heart loses the ability to move blood forward by ventricular ejection, the AV and PV close creating the S2 heart sound. The vigorous contraction, ABP drops. blood will hold in the LA and pulmonary venous system until the onset of the next ventricular diastole when the left ventricular (LV, pressure ~120/O Heart failure in cats is similar to dogs but with some notable differences. mmHg) pressure drops below LA pressure, and the mitral valve (MV) The cause of heart failure in cats may be from any myocardial disease; opens. This allows the O2 rich blood to move from the LA to fill the LV. At hypertrophic cardiomyopathy, restrictive cardiomyopathy, or less com- the onset of the next systole, the LV pushes blood into the aorta (pressure monly dilated and unclassified cardiomyopathies. Valvular heart disease ~120/80 mmHg), where it travels through the systemic circulation to in cats is uncommon. Once CHF has begun, the cause is less important supply nutrients to the body tissues. Once passed the systemic capillary than dealing with the result. An overview of CHF in cats shows that they bed, the blood moves into the systemic venous system and returns to the present one of two ways; “can’t breathe or can’t walk”. The symptoms are RA, initiating the cycle again. usually pulmonary or thromboembolic in nature. The body will attempt to maintain blood pressure preferentially if the Acute treatment of CHF is performed with an injectable diuretic such core organs (heart, brain, and kidney) are in danger. Several components as furosemide and oxygen therapy. An intravenous catheter facilitates of blood pressure regulation are directly related to the heart. Heart rate drug administration and does not need to be large bore since IV fluids (HR) and stroke volume (SV) are the determinants of cardiac output (CO). are not administered. Furosemide is a diuretic that can be administered Cardiac output is the volume of blood flowing over one minute. Cardiac intravenously (IV), intramuscularly (IM) or subcutaneously (SC). The time output multiplied by the systemic vascular resistance (SVR) created in to onset is 5-10 minutes, and the dose range is from 2-6 mg/kg IV. (2,3) It the arterioles combine to make systemic arterial blood pressure. (ABP) is very effective in treating pulmonary edema and the patient usually will Hence, if an arrhythmia changes the heart rate significantly then cardiac have to urinate about 20 minutes post furosemide administration. Diuretic output could be decreased, which decreases blood pressure. Likewise, effects last approximately 2 hours. The pulmonary edema decreases the defects in the mechanical system such as leaky valves, stenotic valves, patient’s ability to oxygenate, and by increasing their fiO2 with oxygen cardiomyopathies, and shunts can all create inefficiencies in the mechani- supplementation hypoxemia can be avoided. Patients with life-threatening cal function of the heart and also decrease ABP. heart failure usually benefit from initial therapy and no other action for the first 15 to 20 minutes. It is important to reduce stress in these cases. The main thurst of cardiac nursing is care of patients with congestive Some patients may even benefit from light sedation with a benzodiazepine heart failure.The term heart failure means the inability of the heart or a mixed receptor opioid. Chronic therapy of CHF relies on transition to to maintain perfusion and blood pressure in the face of adequate oral diuretics, angiotensin-converting -enzyme inhibitor (which supresses or increased preload. This triggers a complex adrenomedullary and RAAS), pimobendan, and spironolactone generally once the patient begins neurohumoral reaction in the body to restore blood pressure. One of eating.Cats usually need the addition of anti-platelet medication such as the most important neurohumoral responses is the activation of the clopidogrel. Renin-Angiotensin-Aldosterone System (RAAS). This system directly and in-directly works to restore blood pressure by sympathetic nervous Pericardial effusion (PCE) is a condition that often presents as an emer- system (SNS) stimulation and fluid retention to increase preload. Initially, gency with cardiac tamponade. Cardiac tamponade describes a condition RAAS does increase blood pressure, but in the presence of a weak heart, in which the pericardial effusion creates pressure in the pericardium the long-term effects are detrimental. The increased volume and chronic greater than that of the RA. (4) The increased pressure causes the RA wall 222 WSAVA GLOBAL COMMUNITY CONGRESS

to collapse during diastole, limiting filling of the right heart and, therefore, 0152 cardiac output to the whole body. A thoracic FAST scan can be used to diagnose PCE.This condition requires counter intuitive therapy. Pericar- COBALAMIN AND COBALAMIN DEFICIENCY diocentesis and recusitation volumes of intravenous fluids are usually J. Steiner needed to treat pericardial effusion. College Station/United States of America Arrhythmias with or without CHF can lead to emergency visits. Both profound tachycardia and bradycardia can cause symptoms. The most Qualifications: common presenting complaint is syncope or collapse. Ventricular tachy- cardia (VT) is the most immediate life-threatening tachycardia. Other Joerg M. Steiner, Dr.med.vet., PhD, DACVIM-SAIM, DECVIM-CA, AGAF tachycardias can lead to heart failure and/or syncope if left untreated, but VT can lead to ventricular fibrillation and death. Atrial fibrillation is University Distinguished Professor common in advanced structural heart disease and may lead to increased severity of CHF. Treatement for VT is considered emergent with ldiocaine Dr. Mark Morris Chair for Small Animal Gastroenterology and Nutrition administered at 2 mg/kg. Atrial fibrillation is usually treated with a calci- um channel blocker such as diltiazem. Director, Gastrointestinal Laboratory Bradycardia, such as Complete or 3rd Degree Atrioventricular Block gilab@cvm.tamu.edu (3AVB) or Sinus Arrest leading to syncope, can present for emergency evaluation. Sympotmatic bradycadia is treated with pacemaker implanta- Summary tion. Cobalamin (vitamin B12) deficiency occurs commonly in both dogs and References: cats with chronic gastrointestinal disease and it is widely accepted that patients may not respond favorably to treatment of the underlying condi- 1 Guyton AC, Lindsey AW. Effect of Elevated Left Atrial Pressure and De- tion unless they are also treated with cobalamin supplementation. Tradi- creased Plasma Protein Concentration on the Development of Pulmonary tionally, cobalamin has been supplemented by parenteral administration, Edema. Circulation Research, 1959 Volume 7, July pp. 649-657. but recent data would suggest that oral cobalamin supplementation may be as efficacious as parenteral supplementation. Given the ease of oral 2 Plumb DC. Furosemide In: Plumb DC. Handbook of Veterinary Drugs administration this mode of supplementation would be much preferable 8th Ed. Ames IA, Wiley-Blackwell; 2015 pp. 643-648 over the parenteral route. 3 Stepien RL. Acute Pulmonary Edema: 5 Steps to Success. Proceed of the Cobalamin Function NAVC; 2005: Orlando. Pp.147. Website: (http://www.ivis.org/proceedings/ navc/2005/SAE/056.pdf?LA=1) Cobalamin is an essential cofactor for several enzyme systems in many mammalian cells. The first enzyme system, methylmalonyl-CoA mutase, is 4 Myers A. Pericardial Effusion and Cardiac Neoplasia. In: Durham, HE, located in the mitochondria and plays a crucial role in the transformation Editor Cardiology for Veterinary Technicians and Nurses. Ames, IA. Wi- of propionyl-CoA to succinyl-CoA. Thus, cobalamin plays a major role in ley-Blackwell; 2017, pp. 302 the metabolism of several amino acids. Cobalamin Absorption Dietary cobalamin is tightly bound to dietary animal-derived protein. In the stomach, dietary protein is partially digested by pepsin and HCl and cobalamin is released. However, cobalamin immediately binds to a transporter protein called haptocorrin or R-protein. Haptocorrin is mostly synthesized and secreted by the gastric mucosa. Haptocorrin in turn is digested by pancreatic proteases in the small intestine. Free cobalamin binds to intrinsic factor. In humans, intrinsic factor is mostly synthesized and secreted by the parietal cells of the gastric mucosa, but there is good evidence that in dogs and cats most of intrinsic factor is synthesized and secreted by pancreatic acinar cells. Cobalamin/intrinsic factor complexes are absorbed by a complex receptor in the microvillus pits of the apical brush border membrane of the ileal enterocytes. Thus, the absorption of cobalamin is an extremely complex system that relies on a multitude of factors and processes. As cobalamin is being absorbed into the intestinal epithelial cells, it dissociates from intrinsic factor and free cobalamin is released into the circulation, where most of it binds to yet another protein, transcobalamin II. The main storage compartments for cobalamin in the body are the liver and the kidney, which maintain serum cobalamin con- centrations by releasing cobalamin whenever needed. Cobalamin Deficiency The most common causes of cobalamin deficiency in dogs and cats are chronic and severe distal or diffuse small intestinal disease and EPI. In addition, short-bowel syndrome, an exclusively vegetarian or vegan diet, or hereditary cobalamin deficiency are less common causes of cobalamin deficiency. 223

13–15 NOVEMBER, 2021 A recent study has shown that 82% of dogs with EPI were cobalamin tration. However, measurement of MMA concentration in serum or urine is deficient. Similar studies in cats have shown that most, if not all, cats with technically involved and expensive. Thus, MMA is currently not routinely EPI are cobalamin deficient. As discussed above, intrinsic factor in dogs assessed in patients evaluated for cobalamin deficiency. and cats is mostly supplied by pancreatic acinar cells. Therefore dogs and cats with EPI may lack enough intrinsic factor for cobalamin absorption. Thus, the only routinely available diagnostic tool to assess cobalamin The lack of pancreatic proteases and the alteration of the small intestinal status in dogs and cats is serum cobalamin concentration, which should microbiota may also play minor roles. be evaluated in every dog and cat with chronic signs of gastrointestinal disease or with clinical signs compatible with cobalamin deficiency that Dogs and cats with severe and long-standing small intestinal disease cannot be attributed to other conditions (i.e., unexplained immunodefi- involving the ileum may also show cobalamin deficiency. In one study, 49 ciencies, anemias, neuropathies). of 80 cats (61%) with chronic signs of gastrointestinal disease had cobal- amin deficiency, as evidenced by a subnormal serum cobalamin concen- Cobalamin Supplementation tration. There appear to be considerable cobalamin stores, but it is unclear where most of the cobalamin stores are located in dogs or cats, but as in Patients with severe cobalamin deficiency often do not respond to therapy humans it takes a considerable amount of time for these body stores to of the underlying gastrointestinal disorder unless or until cobalamin is be depleted if an insufficient amount of cobalamin is being absorbed. being supplemented. As mentioned, patients with low-normal serum cobalamin concentrations should be considered for cobalamin supple- Hereditary cobalamin deficiency has been recorded in a few dog breeds, mentation as measurement of serum cobalamin concentration may not be including the Giant Schnauzer, Beagle, Border Collie, Australian Shepherd, optimally sensitive for the diagnosis of cobalamin deficiency and there is and Chinese Shar Pei. Recently, a region of chromosome 13 has been no indication that over-supplementation of cobalamin leads to complica- identified that cosegregates with cobalamin deficiency in the Chinese Shar tions. The most common form of cobalamin used for supplementation is Pei, but the actual gene causing the disease has not yet been identified. cyanocobalamin, but hydroxocobalamin or methylcobalamin can also be used in patients that don’t respond to cyanocobalamin supplementation Most dogs and cats with cobalamin deficiency only show clinical signs (most of these patients will also fail to respond to other forms of cobal- of gastrointestinal disease, which could either be a cause or the effect amin) or those that appear to have side effects to supplementation with of cobalamin deficiency. Other clinical signs include weight loss, central cyanocobalamin (side effects from cyanocobalamin administration have neuropathies, peripheral neuropathies, or immunodeficiencies. never been definitively demonstrated in either dogs or cats). Traditionally, the standard route of cobalamin application is by parenteral administra- Diagnosis of Cobalamin Deficiency tion. This is because cobalamin deficiency has been shown to lead to cobalamin malabsorption in the ileum. However, there are recent data that A definitive diagnosis of cobalamin deficiency can be challenging. Clinical show that oral supplementation may be as efficacious as parenteral sup- signs are ultimately caused by cobalamin deficiency on a cellular level. plementation. Dosing schedules for parenteral supplementation have been However, the cellular cobalamin status is difficult to assess. Serum described. As for parenteral administration, dosing for oral supplementa- cobalamin concentration has been traditionally measured to help assess tion is empiric with 250 µg of cyanocobalamin being administered orally cobalamin status, but some patients with cobalamin deficiency on a once a day in cats or in dogs up to 10 kg BW, 500 µg in dogs weighing over cellular level do not always have severely decreased serum cobalamin 10 kg but less than 20 kg, and 1000 µg in dogs weighing more than 20 kg. concentrations. Thus, in order to avoid missing patients with cobala- Daily supplementation is required and after a 3-months period one should min deficiency, cobalamin supplementation should be considered even discontinue supplementation for about a two weeks and recheck serum when serum cobalamin concentration is low normal. Several assays for cobalamin concentration. the measurement of serum concentrations of cobalamin in humans are available. In order to be used in dogs and cats, these assays designed for In one large retrospective study of 51 client-owned dogs with low-normal use in humans must be validated for use in dogs and cats. The GI Lab at or subnormal serum cobalamin concentrations patients were supplement- Texas A&M University has analytically validated an automated chemilu- ed with oral cyanocobalamin (250-1000 µg cobalamin orally once a day) minescence assay designed for the measurement of cobalamin concen- and serum cobalamin concentrations increased in all of the dogs. Simi- trations in humans for use in dogs and cats. A reference range for serum larly, a recent study looked at oral cobalamin supplementation in geriatric cobalamin concentration in dogs and cats was established. Reference cats, only some of which were actually cobalamin deficient. Similarly to ranges are not transferrable between labs and each lab should establish the study in dogs serum cobalamin concentrations increased significantly their own reference range. with oral supplementation. Also, more recently a small retrospective study in 16 cats with chronic enteropathy or intestinal lymphoma and low or Serum or urine methylmalonic acid (MMA) concentration can also be low-normal serum cobalamin concentrations showed dramatic increases used as an indicator of cobalamin status. Cobalamin deficiency leads in serum cobalamin concentrations in all 16 cats. to accumulation of MMA and thus concentrations of MMA are often dramatically increased in the serum or urine of patients with cobalamin deficiency. Serum MMA concentrations have been shown to be increased in cats with cobalamin deficiency and have been shown to decrease with cobalamin supplementation. Also, recently dogs with severely decreased serum cobalamin concentrations were shown to have increased serum MMA concentrations. Interestingly, several dogs with low-normal serum cobalamin concentrations were also shown to have increased serum MMA concentrations, demonstrating that a severely decreased serum cobala- min concentration is not optimally sensitive for the diagnosis of cobala- min deficiency on a cellular level and that a cut-off value for cobalamin supplementation should be chosen that is in the low-normal reference range. This is especially true if one considers that cobalamin supplemen- tation is minimally invasive, safe, and relatively cheap. As suggested by these data, measurement of serum MMA concentration may be a better diagnostic test for cobalamin deficiency than serum cobalamin concen- 224 WSAVA GLOBAL COMMUNITY CONGRESS

0153 serum folate concentration a decreased serum cobalamin concentration is not specific for intestinal dysbiosis. Any severe small intestinal disease DYSBIOSIS AND FECAL MICROBIOTA involving the ileum can lead to cobalamin deficiency. Also, a lack of intrin- TRANSPLANTATION sic factor and digestive proteases in dogs with exocrine pancreatic insuf- ficiency can cause cobalamin deficiency. A decreased serum cobalamin J. Steiner concentration is rather insensitive for intestinal dysbiosis and in one study only 25% of dogs with intestinal dysbiosis had decreased serum cobala- College Station/United States of America min concentrations. A combination of a decreased serum cobalamin and an increased serum folate concentration is highly specific for intestinal Qualifications: dysbiosis but rather insensitive. These two parameters are to date the most practical diagnostic tools for the diagnosis of intestinal dysbiosis. Joerg M. Steiner, Dr.med.vet., PhD, DACVIM-SAIM, DECVIM-CA, AGAF The GI Lab at Texas A&M University has recently developed PCR based University Distinguished Professor assays that are able to measure the fecal abundances of some key bacte- rial groups. A mathematical algorithm is used to report these changes as Dr. Mark Morris Chair for Small Animal Gastroenterology and Nutrition a single numerical value; the so called dysbiosis index (DI). A negative DI indicates normobyosis, whereas a positive DI indicates dysbiosis. The DI Director, Gastrointestinal Laboratory was specifically trained to diagnose the dysbiosis associated with chronic enteropathy in dogs and an increased DI in dogs with chronic enteropathy gilab@cvm.tamu.edu provides additional information during the diagnostic work-up of these dogs. Introduction Treatment The microbiota is the collection of all microorganisms in the GI tract, in- cluding viruses, bacteria, and fungi. A physiologic microbiota is essential The therapeutic goal in dogs with dysbiosis is the identification and treat- for gastrointestinal and overall health of the host. Intestinal dysbiosis ment of a possible inciting cause. For example, serum TLI concentration describes a situation where the intestinal microbiota is altered in either should be evaluated. If a primary cause cannot be identified one of several composition or numbers, which can lead to clinical signs of gastroin- therapeutic strategies or a combination thereof should be employed. testinal disease. There are several different terms that describe similar clinical conditions: antibiotic-responsive diarrhea (ARD), tylosin-respon- Fecal transplantation sive diarrhea, small intestinal bacterial overgrowth (SIBO), and intestinal dysbiosis. Intestinal dysbiosis is probably the best term and will be used In humans with chronic intestinal disease there has been some experience for the remainder of this presentation. with fecal transplantation. This procedure can aid in restoration of the normal microbiota. FMT is the transfer of stool from a healthy donor into Etiology the gut of a recipient via oral capsules, endoscopy, or enema. For FMT, a healthy donor has to be chosen – this requires careful assessment of Intestinal dysbiosis is caused by an abnormal proliferation of bacteria the potential donor. While there are currently no universal guidelines for and/or the change in bacterial species present in the intestinal lumen. this, the author recommends a complete medical history and a thorough However, dysbiosis should not be considered a primary disorder in most physical examination to rule out signs of gastrointestinal or systemic dis- if not all patients with this disorder. There are several protective mech- ease, screening for enteropathogens and intestinal parasites, a minimum anisms that prevent a patient from dysbiosis. Gastric acid, intestinal database (CBC, chemistry profile, urinalysis), serum concentrations of motility, and antibacterial activity of pancreatic juice all limit the bacterial cobalamin and folate, and a fecal dysbiosis index. The feces are ideally numbers in the small intestine. Any disease process that affects one or collected fresh, diluted with some water, blenderized, strained, and admin- more of these protective mechanisms. istered to the patient. It is currently unknown whether stored FMT (e.g., freeze dried, frozen) is equally beneficial as is fresh FMT. Also, the optimal Clinical Findings route of administration is unknown, although the majority of anecdotal applications has been through enemas. Most patients will require repeat Intestinal dysbiosis in dogs and cats leads to chronic small bowel diar- application for sustained response to therapy. Thus, there are many open rhea that is often intermittent. Weight loss can be present in some cases. questions concerning the exact protocols and associated efficacy for FMT Other clinical signs maybe due to the primary underlying disease process, in small animal patients. such as partial obstruction, exocrine pancreatic insufficiency, or others. Diagnosis Part of the controversy about intestinal dysbiosis is due to the fact that this disorder is difficult to diagnose. Traditionally, the gold standard for assessment of the intestinal bacterial ecosystem is bacterial culture, but it is now recognized that this does not allow for accurate characterization of the intestinal microbiota. Serum folate concentration – folate is synthesized by enteric bacteria and is available for absorption. In dogs with intestinal dysbiosis for a long pe- riod of time, serum folate concentration can increase. While an increased serum folate concentration is fairly specific for intestinal dysbiosis, it is not very sensitive. In one study only 50% of all dogs with intestinal dysbio- sis had increased serum folate concentrations. Serum cobalamin concentration - Many species of bacteria utilize cobal- amin and compete with the body for dietary supplies. Unlike an increased 225

13–15 NOVEMBER, 2021 0154 serum bile acids are once again measured. Very little food is required to stimulate CCK release and gall bladder contraction and thus the test DIAGNOSTIC USE OF BILE ACIDS should be meaningful even in patients with a poor appetite. J. Steiner In healthy dogs and cats, baseline serum bile acids concentrations should be within the reference interval. After gall bladder stimulation serum College Station/United States of America bile acids concentrations should slightly rise. This is why the reference interval for postprandial serum bile acids concentrations is usually slightly Qualifications: higher than that for baseline values for most commercial laboratories and in-house analyzers. However, in many patients, baseline and postprandial Joerg M. Steiner bile acids concentrations are very similar. Dr.med.vet., PhD, DACVIM-SAIM, DECVIM-CA, AGAF Paradoxical Results University Distinguished Professor As mentioned above, in healthy dogs and cat’s postprandial serum bile acids concentrations should be slightly higher than baseline values. Dr. Mark Morris Chair for Small Animal Gastroenterology and Nutrition However, in about 20% of dogs and cats, postprandial serum bile acids concentrations are actually lower than baseline values and many clini- Director, Gastrointestinal Laboratory cians initially suspect a laboratory error. A preprandial serum bile acids concentrations that is lower at the postprandial sample than the baseline gilab@cvm.tamu.edu sample can be interpreted as a paradoxical result as long as both results are within the reference interval for the postprandial measurement. Introduction Traditionally, it had been hypothesized that paradoxical bile acids results The measurement of serum bile acids concentrations (SBAs) has been uti- happen because the dog or cat sees, smells, or thinks of food prior to lized as a diagnostic test to assess hepatic function for many years. Mea- collection of the baseline sample. However, in a study in which eight surement of SBAs can be a marker of global hepatic failure, as it occurs in healthy dogs were held off food for 12 hours and then a bowl of wet food patients with hepatic cirrhosis, but also in patients with a portosystemic was placed in front of their cage for 20 minutes, but then removed without vascular anomaly. If utilized as a dynamic test, the measurement of serum feeding the dogs, no specific patterns of serum bile acids concentrations bile acids concentrations can be used to differentiate between different could be observed. Thus, it would appear to be more likely that the migrat- types of patients as it relates to the underlying cause of the liver disease. ing motor complex leads to intermittent gall bladder contractions during This session will summarize the physiology and diagnostic utility of the the interdigestive phase, leading to paradoxical results. measurement of serum bile acids concentrations. The Patient With Liver Failure Serum Bile Acids Concentrations in Healthy Dogs and Cats When hepatic function is significantly impaired, extraction of bile acids Bile acids are synthesized in hepatocytes of all mammalian species from the portal blood becomes less efficient and both pre- and postpran- from cholesterol. The primary bile acids that are being synthesized vary dial SBAs increase. Feeding of a dog or cat with liver failure, for example between species and may include, for example, cholic acid. These primary due to cirrhosis, leads to contraction of the gall bladder and release of bile acids are then conjugated with an amino acid, glycine or taurine, to bile acids into the intestines. These get absorbed in the ileum and reach form, for example, glycocholic acid or taurocholic acid. These conjugat- the liver via the portal vein. Normally, hepatocytes would extract these bile ed bile acids are then secreted into the biliary canaliculi that ultimately acids from the portal blood with high efficiency during the first pass, but in collect into the common bile duct. There is a side arm of the common bile patients with liver failure, the bile acids remain in the blood and leave the duct, the cystic duct, that connects the common bile duct to the gall blad- liver via the hepatic vein, leading to very high serum bile acids concen- der. Bile collects in the gall bladder over time and is being concentrated. trations postprandially. The blood comes back to the liver as the blood When an animal ingests a meal that contains fat, the presence of fat in the circulates back to the liver through the hepatic artery, but no matter how small intestines leads to release of cholecystokinin (CCK) from neuroen- often the bile acids pass by the hepatocytes these cells are not efficiently docrine cells in the small intestinal mucosa. In turn, CCK stimulates the removing the bile acids from the blood, leading to increased baseline contraction of the gall bladder and release of bile containing bile acids bile acids concentrations even 12-hours after feeding and beyond. This into the small intestines. Some bile acids are being deconjugated in the explains the typical pattern for SBAs for patients with liver failure with small intestines to form unconjugated bile acids. Both conjugated and both baseline and postprandial SBAs being very high. unconjugated bile acids can be absorbed in the ileum and can undergo enterohepatic circulation. The Patient With a Portosystemic Vascular Anomaly It should be noted that bile acids can be quantified in various ways. For In patients with a portosystemic vascular anomaly, pre-prandial SBAs example, for metabolomic analysis, each primary and secondary bile acid maybe only slightly increased, while post-prandial SBAs often are severely is measured separately by gas chromatography followed by mass spec- increased. Similarly, to patients with classical liver failure, feeding of a trometry. This kind of analysis is labor intensive and rather expensive and, dog or cat with a portosystemic vascular anomaly, leads to contraction at the current time, is limited to research applications. However, serum of the gall bladder and release of bile acids into the intestines. These get bile acids concentrations can also be measured more globally, using a absorbed in the ileum and are carried away in the blood of the portal vein. biochemistry analyzer or newer patient-side analyzers. When utilizing However, in patients with a portosystemic vascular anomaly, a portion of such assays, we quantify the total amount of bile acids in the serum, both the blood does not go to the liver and thus hepatocytes are not receiving conjugated and unconjugated. the bile acids to extract them from the blood. Thus, in patients with a portosystemic vascular anomaly the bile acids remain in the blood leading Also, the measurement of serum bile acids concentrations is traditionally to very high serum bile acids concentrations postprandially. The blood used as a dynamic test. In other words, the patient is held off food for comes back to the liver as the systemic blood circulates back to the liver a minimum for 12 hours. A baseline blood sample is collected and the through the hepatic artery and the hepatocytes extract the bile acids from patient is then fed a small quantity of a fatty food to stimulate gall bladder contraction, and two hours later a second blood sample is collected and 226 WSAVA GLOBAL COMMUNITY CONGRESS

the arterial blood. Thus, as time goes by, SBAs decrease and might even 0155 reach values within the reference interval or slightly above the upper limit of the reference interval at the time of measurement of the pre-prandial ETHICS AND EMERGING DIGITAL TECHNOLOGIES IN value. VETERINARY MEDICINE S. Coghlan It is important to note, that while these patterns can be helpful in arriving at a diagnosis, they are not definitive. For example, patients with a por- Melbourne/Australia tosystemic vascular anomaly may develop hepatic dysfunction over time and both baseline and postprandial serum bile acids concentrations may Qualifications: be very high. Simon Coghlan When to Request Serum Bile Acids Measurements PhD, BVSc In patients with increased serum hepatic enzyme activities, SBAs can help to assess global hepatic function. In addition, the pattern of serum bile simon.coghlan@unimelb.edu.au acids concentrations may also help to further hone in on the definitive Ethics and emerging digital technologies in veterinary medicine diagnosis. While serum bile acids concentrations are most useful when utilized as a dynamic test, in other words both measuring pre-prandial Simon Coghlan PhD, BVSc (i.e., baseline and post-prandial bile acids), an increased SBAs concentra- tion postprandially does at least provide some information about global WSAVA conference November 2021 hepatic dysfunction. Introduction However, SBAs concentrations have a limited specificity and thus measur- ing them in dogs and cats with no suspicion of liver disease may lead to Emerging technologies such as Artificial Intelligence (AI) and machine false positive results that then need to be further worked-up. learning (ML) are already having some impact in human medicine. Cut- ting-edge technologies may advance medicine, but also carry risks (1). In addition, patients with cholestasis always have increased SBAs con- Although migration of emerging technologies into veterinary medicine is centrations and thus SBAs should not be evaluated in hyperbilirubinemic relatively slower, it is likely to accelerate. We should start thinking now patients. about the ethical issues. Some patients with small intestinal dysbiosis may have increased serum Emerging technologies unconjugated bile acids concentrations that are high enough that SBAs are increased above the upper limit of the reference interval. However, Increases in computing power and sensors have enabled smarter systems these patients should only have mild increases of SBAs and a small to emerge. For example, smartphones contain accelerometers, GPS increase after stimulation of gall bladder contraction. systems, gyroscopes, light sensors. Wearables can continuously record in- formation like heart rates, O2 levels, and activities (e.g. sleeping, walking, eating). Big Data has allowed AI to get more powerful. Machine learning (ML) is a statistical process for making predictions, classifications, and decisions. Data (inputs) are algorithmically processed to produce predictions etc. (outputs). Inputs could include images, medical records, pathology results, ambient data, etc. Such AI learns from training data and devises an algorithmic model of its own, and is in this sense autonomous. Digital veterinary medicine AI can make predictions or decisions about triage, diagnosis, prognosis, treatment. ML has been experimentally applied to various areas of small animal veterinary medicine. For example, a machine learning algorithm was reported to have a sensitivity of 96.3% and a specificity of 97.2% in screening dogs for hyperadrenocorticism (HPA). Reportedly, this AI screening tool outperforms other screening methods (2). ML has been designed for detecting or classifying abnormalities like can- cer, retinal atrophy, and colitis from images and slides (3). Radiological ML has been used to identify cardiac enlargement (4). Some ML models can already outperform veterinary radiologists and pathologists (5) . AI ethics principles Various organisations have fashioned ethical principles to guide AI use (6). Some can be usefully applied to animals. AI scholars highlight the notion of trustworthiness (1). A given automated medical system should be trustworthy so that users are right to rely on it when it could help them fulfil certain responsibilities. Acute questions of fairness have arisen with human AI. For example, AI 227

13–15 NOVEMBER, 2021 used in policing and job recruitment has been heavily criticised. Bias in nal of the American Medical Informatics Association. 2021;28(4):890–4. machine decision-making can occur when training data is problematic. This can lead to automated decisions that penalise minoritized groups. 2. Reagan KL, Reagan BA, Gilor C. Machine learning algorithm as a diag- nostic tool for hypoadrenocorticism in dogs. Domestic Animal Endocrinol- So-called ‘black box’ AI lacks transparency. Deep learning employs arti- ogy. 2020 Jul;72:106396. ficial neural networks that make it impossible to fully understand how a prediction was made. Another AI principle is accountability, or the need to 3. Zuraw A, Aeffner F. Whole-slide imaging, tissue image analysis, and assign responsibility for AI to the right parties. artificial intelligence in veterinary pathology: An updated introduction and review. Vet Pathol. 2021 Sep 14;03009858211040484. Veterinary ethics 4. Li S, Wang Z, Visser LC, Wisner ER, Cheng H. Pilot study: Application of Veterinarians generally aim to improve patient wellbeing for the sake artificial intelligence for detecting left atrial enlargement on canine thorac- of those patients. Veterinarians are also typically ethically motivated to ic radiographs. Veterinary Radiology & Ultrasound. 2020;61(6):611–8. benefit their clients. Practitioners consider it important to continually improve their professional services to benefit patients and clients. Main- 5. Boissady E, de La Comble A, Zhu X, Hespel A. Artificial intelligence eval- taining personal wellbeing is also important, partly because professional uating primary thoracic lesions has an overall lower error rate compared to performance can be affected by stress and burnout. Technologies that veterinarians or veterinarians in conjunction with the artificial intelligence. benefit patients, clients, and vets are prima facie desirable; technologies Vet Radiol Ultrasound. 2020 Nov;61(6):619–27. that harm them are not. 6. Jobin A, Ienca M, Vayena E. The global landscape of AI ethics guide- Possible benefits of emerging technologies lines. Nature Machine Intelligence. 2019 Sep;1(9):389–99. Some digital technologies promise to be less invasive for patients. In 7. Poplin R, Varadarajan AV, Blumer K, Liu Y, McConnell MV, Corrado GS, et humans, cardiovascular risk factors may potentially be divined from subtle al. Prediction of cardiovascular risk factors from retinal fundus photo- retinal changes using deep learning (7). Similar relatively non-invasive graphs via deep learning. Nat Biomed Eng. 2018 Mar;2(3):158–64. techniques may be used in animals. For example, sensors may be used to detect lameness, behavioural disturbance, or neurological issues in 8. Quinn TP, Jacobs S, Senadeera M, Le V, Coghlan S. The three ghosts comfortable home settings. of medical AI: Can the black-box present deliver? Artificial Intelligence in Medicine. 2021 Aug 28;102158. ML may prove more competent in some domains than are most veterinari- ans. Because AI can sometimes detect invisible disease-relevant features, it may facilitate improved screening, prevention, and early intervention. AI medical analyses can be fast and convenient. Getting input on clinical cases from journals, pathologists, radiologists, and specialists can take time. If AI could speed up decision-making, it might benefit patients and reduce vet stress, allowing practitioners to spend more time with patients and clients and in self-care. Concerns about emerging technologies Veterinary AI has been explored experimentally in laboratory settings. This may not translate to actual patient benefits. If ML algorithms are trained on biased data, they may fail in real-life. Consider a ML model trained on data from beagles applied to other dog breeds. Any resulting bias could generate false positive or negative outputs harmful to patients. AI needs to be validated outside the lab (1). Concerns of insufficient transparency may also be raised about deep learning algorithms. It may, for instance, be impossible to know exactly why a deep learning system predicts that a dog or cat has disease X, a prognosis of Y months, or a need for drug Z. This may fail to satisfy clients who want to understand the reasons. Powerful AI may encourage veterinarians to over-reliance. One possible problem here is the gradual erosion of medical skills. Another is that complex ethical decisions could be improperly avoided. Digital technologies could exacerbate stress through information over- load. Finally, since automated decision-making may lack transparency, there could be a problem of accountability. If AI kills a patient due to a flawed recommendation, who is responsible: the veterinarian, designer, or company? Vets and boards may ask whether and how ‘black box’ medical AI should be employed (8). References 1. Quinn TP, Senadeera M, Jacobs S, Coghlan S, Le V. Trust and medical AI: the challenges we face and the expertise needed to overcome them. Jour- 228 WSAVA GLOBAL COMMUNITY CONGRESS

0156 Bernard Rollin, a pioneer in this field, describes the fundamental question of veterinary ethics as whether the veterinarian’s primary obligation is to ETHICALLY CHALLENGING SITUATIONS IN the animal, or the animal owning client. VETERINARY CLINICAL PRACTICE A global survey of veterinary team members undertaken during the early A. Quain months of the COVID-19 pandemic found that, in addition to those ECS previously reported in major surveys, common ethical challenges included Sydney/Australia conflict between personal wellbeing and professional role, challenging decisions about what counts as an essential veterinary service, conflict Qualifications: between the wellbeing of household members and professional role, and whether to perform non-contact vet visits (1). Additionally, among the Anne Quain most stressful ECS was conflict between the interests of my employer and my own interests. BA (Hons) BSc(Vet)(Hons) BVSc(Hons) MVS GradCertEdStud (HigherEd) MANZCVS (Animal Welfare) DipECAWBM The most common barriers to resolving an ECS to one’s satisfaction were: pressure from an employer or client; financial limitations; differences in anne.quain@sydney.edu.au values between stakeholders; lack of time and communication difficulties. ETHICALLY CHALLENGING SITUATIONS IN VETERINARY CLINICAL PRAC- In addition, workplace policies were the sixth most frequent barrier to TICE resolving ECS. What is an ethical decision? The most common resources that veterinary team members used to help resolve an ECS were: discussions with colleagues; policies from their An ethical decision is one that has the potential to impact the welfare of work (this was also experienced as a barrier by some); reference to the others; is generally given priority over other decisions; and is a decision code of conduct or oath; discussion with a spouse or partner or use of a which is typically justified according to values, principles and frameworks. decision-making framework. What is an ethically challenging situation? In the early stages of the COVID-19 pandemic, we found that being a veterinary nurse or veterinary technician, working in companion animal An ethically challenging situation (ECS) is a situation where we are practice, working in North America or Canada, or being not-confident required to manage competing choices, or where there may be conflict or underconfident in dealing with ethically challenging situations were between the interests of different stakeholders or parties who may be associated with an higher risk of experiencing an increase in frequency impacted by a decision. of ECS, relative to being a veterinarian, working in non-clinical practice, working in Australia or New Zealand, or being confident or very confident Ethically challenging situations are encountered by all members of the in resolving ECS. veterinary team – veterinarians, veterinary nurses, veterinary technicians, practice managers, animal attendants. It is important to stress that ethical Years of experience, gender, ethics training, hours worked and autonomy challenges are experienced by veterinary team members working in in making ethical decisions were not significantly correlated with increase non-clinical roles (for example, those working for the Government, NGOs, in ECS during the early months of the pandemic. in education and training, public health an so on). What can we do? Why should veterinary team members, educators and professional organi- sations be concerned about ECS? Our findings suggest a need to train and support veterinary team members in managing ECS encountered during the pandemic, as well as those ECS Surveys have shown that ECS are common in veterinary settings, and documented in previous surveys. are a source of stress (1). ECS give rise to a type of stress known as moral stress, which – if a person feels they are not able to do what they Additionally, some key barriers to resolving ECS, such as pressure from consider the “right” or best thing, or if they act in a way that transgresses employers or clients, differences in values between stakeholders and their deeply values – can lead to moral distress. Some authors argue that communication difficulties MAY be addressed by further training in burnout, a common affliction among veterinary team members, is actually communication and conflict management. Risk factor analysis suggests a form of moral injury or the consequence of severe moral distress (2). that we need to focus on equipping nurses and veterinary technicians to Moral stress, moral distress, moral injury or burnout may contribute to navigate ethical challenges or communicate their concerns if they are not career attrition, psychological morbidity, and potentially mortality, in able to make decisions. veterinary professionals (3). As the primary resource used in approaching ethical challenges was What types of ECS do veterinary team members encounter? talking to colleagues, improved training of veterinary teams in ethical debriefing may assist. A number of surveys have been undertaken to identify the frequency, stressfulness and types of ECS encountered in veterinary clinical settings In human health care, a range of interventions, from critical incident (1, 4-9). debriefing and professional supervision to ethics rounds are used to help reduce moral distress, and improve ethical reasoning. Ethics rounds The majority of surveys have focused on ethical challenges encountered involves discussing ethical aspects of cases with team members after the by veterinarians working in clinical practice, particularly those working in fact. We are piloting ethics rounds with veterinary teams. companion animal practice. Therefore it is important to expand the field of enquiry to incorporate other veterinary team members, and those working The 90-minute, online sessions comprise 4-10 participants, in addition outside of companion animal practice, as well. to a facilitator. We are administering a slightly modified version of the Euro-MCD, or moral cognitive deliberation score, which was developed to The most common ECS is how to proceed when clients have financial assess the impact of ethics rounds in healthcare (10). This questionnaire limitations. Other common ECS include conflicts between the interests of is administered before the after the session. This will facilitate compari- the client and the interests of the animal. Perhaps this is why Professor son of scores before and after to determine whether there is a change, for 229

13–15 NOVEMBER, 2021 example in ability to recognise an ethically challenging situation. 0157 An expanded fundamental question of veterinary ethics? CANINE BREEDING MANAGEMENT VS MISMATING Veterinary team members work in a range of contexts. Not all ECS involve N. Krekeler conflicts involve the conflict between the interests of an animal and the interests of a client. In the case of wildlife or stray animals, for example, Victoria/Australia there may be no client at all. In the case of antimicrobial resistance, stake- holders may include different populations and species, persons who are Qualifications: not clients of veterinary services, and even the environment. Natali Krekeler Perhaps what we need from veterinary ethics is some help answering the question: What would a “Good” veterinary team member do? …in this sit- Dr. med. vet., PhD, DACT uation, in this context, with the skills, knowledge, and resources available to them? krekeler@unimelb.edu.au Breeding management and mismating Despite one’s best efforts, one – even the Good vet – can be wrong. Natali Krekeler Human error, overlooking one or more stakeholders, failure to predict unin- The University of Melbourne tended consequences and so on can lead to near misses, poor outcomes Melbourne, Australia and/or transgression of personal values. Monitoring the canine oestrous cycle closely to optimize breeding man- The Good veterinary team member reflects on and seeks to learn from agement is recommended to achieve optimal conception rates and litter these experiences. It is a position that requires ethical humility. size. Same principles can be used to improve management of mismating. Tools to determine the stage of the oestrous cycle References Test for “breeding reflexes”: Stimulation of the perineal area will result in “flagging” (lateral deviation 1. Quain A, Mullan S, McGreevy PD, Ward MP. Frequency, Stressfulness of the tail) and “winking” (upward tipping of the vulva). Lumbar pressure and Type of Ethically Challenging Situations Encountered by Veterinary will result in “lordosis” (standing firmly and arching of back); note vaginal Team Members During the COVID-19 Pandemic. Frontiers in veterinary discharge science. 2021;8(311). Vaginoscopy: Vaginoscopy is best performed using a vaginal speculum made from plexi- 2. Dean W, Talbot S, Dean A. Reframing Clinician Distress: Moral Injury Not glass and a strong light source. An endoscope can also be used. Along Burnout. Fed Pract. 2019;36(9):400-2. with being useful for monitoring the oestrous cycle, it is also essential for diagnosing several genital disorders. 3. Arbe Montoya AI, Hazel SJ, Matthew SM, McArthur ML. Why do During oestrous monitoring the vaginal wall and its mucosal folds (plicae) veterinarians leave clinical practice? A qualitative study using thematic are assessed. analysis. Veterinary Record. 2021;188(1):e2. Cytology: Exfoliative vaginal cytology is a valuable clinical method to monitor the 4. Batchelor CEM, McKeegan DEF. Survey of the frequency and perceived oestrous cycle as changes in cytology closely follow endocrinological stressfulness of ethical dilemmas encountered in UK veterinary practice. events. For a representative sample harvest cells from the cranial vagina. Veterinary Record. 2012;170(19). This is best done at the time of vaginoscopy through the speculum with a saline moistened cotton swab. The cotton swab should be rolled in 5. Crane MF, Phillips JK, Karin E. Trait perfectionism strengthens the nega- several non-overlapping rows over a glass slide and the slide air dried. tive effects of moral stressors occurring in veterinary practice. Australian “Modified or rapid Wright Giemsa stain can be used for staining. Veterinary Journal. 2015;93(10):354-60. The major cell types present are: 6. Kipperman B, Morris P, Rollin B. Ethical dilemmas encountered by small non cornified cells animal veterinarians: characterisation, responses, consequences and beliefs regarding euthanasia. Veterinary Record. 2018;182(548). parabasal cells: small, round – oval, “fried egg” appearance 7. Moses L, Malowney MJ, Wesley Boyd J. Ethical conflict and moral intermediate cells: larger than parabasal cells, higher cytoplasm : nuclear distress in veterinary practice: A survey of North American veterinarians. ratio Journal of Veterinary Internal Medicine. 2018;32(6):2115-22. cornified cells 8. Dürnberger C. Am I actually a veterinarian or an economist? Under- standing the moral challenges for farm veterinarians in Germany on the superficial cells: pyknotic nuclei, angular shape to the cytoplasm basis of a qualitative online survey. Research in Veterinary Science. 2020;133:246-50. anuclear squamous cells: anuclear, largest of vaginal epithelial cells, resemble “cornflakes” 9. Lehnus KS, Fordyce PS, McMillan MW. Ethical dilemmas in clinical practice: A perspective on the results of an electronic survey of veterinary Cells that can be present: erythrocytes, bacteria (especially early in anaesthetists. Veterinary anaesthesia and analgesia. 2019;46:260-75. prooestrus) BUT inflammatory cells (especially bacteria phagocytosing cells) should not be seen in oestrus as they would originate from uterus 10. de Snoo-Trimp JC, de Vet HCW, Widdershoven GAM, Molewijk AC, (-> warrants further work up). Svantesson M. Moral competence, moral teamwork and moral action - the European Moral Case Deliberation Outcomes (Euro-MCD) Instrument 2.0 and its revision process. BMC Medical Ethics. 2020;21(1):53. Serum hormone levels: Although, LH surge detection by measuring luteinizing hormone (LH) is 230 WSAVA GLOBAL COMMUNITY CONGRESS

considered the gold standard, it is often not practical in clinical settings. < 70% cornified As the LH surge varies in length from 24 to 60 h, it can be missed if blood sampling is not undertaken daily at the same time. Exfoliative vag- iaieopnscmdnnuerruaefctiylpcmrxesnlrtastreqrehoubebm;rarunrafeaopsiae-esrcscceemdeiaooyorsaicstloffarleenautecwasneinspofnhtidacireadcitnnledghseeaidleefmllnilslesiuaadclllle-cnmtsa>obchmoeeer9vaalurial0peynnnstga%rri;nisfeoirniEnomseporatepdhfyalnbrticleolshtelseepomriloprniseltescrhnhsoeayouteiesnrrtumlueesialsstndblr;teonruosstnpe1dco“ocpnmeapeolr/iffaaelnuinlpeDltstsest-heetfm1ceruo;eoro/onaklceluap~oitnoresanrnhLfdc(ntgldiinrHynftlecupiseatioe8esean)ungdn;lsrtupelctia-srnihcmre(onboemcoeolptaflbsrrenshacseneeriyaiaDnirmlnftsslsitaolee;yey-d- As a proxy, the initial rise in the serum or plasma progesterone concentra- inal cytology tion (> 1.5- 2ng/ml) has been widely used for the determination of the LH surge, with the radioimmunoassay still being considered most accurate.1 cells) Endocrinologically, the LH surge marks the beginning of oestrus. In a large study of 1300 individual bitches, the mean progesterone concentration day of the LH surge (±SD) at the time of the LH surge was found to be 2.7 ±0.6 ng/ml, indepen- dent of breed and body weight.2 is defined as the first Ovulation occurs approximately 2 days after the LH peak. Canine oocytes are ovulated as primary oocytes and need to go through a phase of mat- starts at baseline (< day ofoestrus (day 0/ uration before they can be fertilized. It takes 48 to 72 hours for them to undergo meiotic division to become secondary oocytes. 0.2ng/ml). increase d0/ LH0). Plasma pro- peak between 20 – 90 Peak progesterone levels in dioestrus are extremely variable in the bitch in late prooestrus, gesterone levels beginng/ml by 15 to 30 and therefore not suited to estimate the gestational age. The corpora lutea are the main source of progesterone throughout the pregnancy and Serum proges- when luteinization of to increase slowly in days after the LH ovariectomy or luteolysis in the pregnant bitch will result in termination of the pregnancy. terone levels praeovulatory follicles late prooestrus but surge Serum progesterone levels in the pregnant and the non-pregnant bitch are almost the same with non-pregnant bitch not having a sharp decline begins suddenly double the of progesterone at the end of dioestrus. This is suggesting that the bitch is lacking a luteolytic mechanism, which distinguishes her from other time of the LH surge domestic species. (> 1.5 ng/ml). BEWARE! Whole blood should not be chilled prior to centrifugation as Lower case “d” refers to LH surge, upper case “D” refers to dioestrus this affects the accuracy of the assay. Ideally, it should be kept at room (therefore, d0 = D -8), e.g. temperature and centrifuged as soon as possible. Serum can be stored at – 20 degrees Celsius. 3 d0 or LH0: day of the LH surge (based on serum progesterone or LH levels) Prooestrus Oestrus Dioestrus d1-7 or LH1-7: days of oestrus in relation to LH surge D1 or ~LH8: first day of dioestrus (based on cytology) Breeding males are attracted become pronounced usually subside of reflexes to bitch in prooestrus; around the time of LH within three days Breeding Management bitch usually not re- surge, onset can vary dioestrus onset ceptive to mating yet from 3 days before to At the first sign of prooestrus (vulvar swelling/ bleeding), take first vaginal 5 days after LH surge smear for cytology and a serum sample for progesterone determination. Keep doing this every other day until the serum progesterone indicates it vulvar turgidity peaks Vulva less turgid; dis- is the time of the LH surge. Stop cytology at the first day of dioestrus (D1). Vulva and in late prooestrus; charge more serous When to breed depends on the method of mating: discharge Oocytes remain viable for 2 to 3 days. That means that on d6/ LH6 some serosanguineous (straw colour); stays “diestrus dumping” oocytes can begin to show signs of degeneration. An additional serum sample for progesterone measurement should be taken at the time of D1 discharge changing to (sero)sanguineous in (can be frozen in case of non-pregnancy). serous later some bitches Natural mating: Bitches should be mated every other day from d3 of oestrus until the first Vaginoscopy decreasing oedema. day of dioestrus pronounced wrinkling/patchy, hyperaemic (D1). Alternatively, let them mate on d3 and 5 or d4 and 6, if the stud dog crumpling of vaginal appearance of vaginal is in high demand or other restraints limit the frequency. oedematous moist, folds (crenation); wall and crenation dis- Dog semen can survive up to 10 days (average 6 days) in the female repro- pink vaginal folds. Ad- findings progress appears; vaginal folds ductive tract. Therefore, a mating between two days before the LH surge ditional folds develop during oestrus; vagi- become; rounded, (d -2) until d 6 of oestrus can result in high conception rates. Multiple in cranial vagina nal wall is pale-pink, clear to gray mucus males can sire the same litter (superfecundation). small amount of strawcan be present in coloured fluid often copious amounts present Artificial insemination: fresh and chilled semen: insemination either on d3 and d5 or day d4 and d6. 231

13–15 NOVEMBER, 2021 frozen semen: depending on how many doses are available; 0158 if only one dose is used: insemination on d5 CLINICAL USE OF REPRODUCTIVE HORMONES S. Romagnoli if two doses are used: inseminaton on d4 and d5 or d5 and d6. Legnaro/Italy Frozen semen has a limited life span (only up to 24 hours). Therefore, it should be deposited into the uterus the closest to d5. Mismating Qualifications: Only 40-70% of bitches presented for mismating are actually pregnant, therefore it is prudent to diagnose pregnancy prior to treatment. To ensure Stefano Romagnoli early, reliable pregnancy examination at around 28 days after the LH surge (LH28) it is important to examine the bitch as soon as mismating has oc- DVM, MS, PhD, Dipl ECAR curred. At the first visit breeding reflexes and the serum progesterone lev- el should be assessed and a vaginoscopy and exfoliative cytology should stefano.romagnoli@unipd.it be performed. The presence of sperm on the cytology should be noted, but an absence of sperm does not rule out mismating. A vaginal speculum PROSTAGLANDINS exam and an exfoliative cytology should then be performed every other day until the first day of dioestrus is diagnosed. An ultrasound exam can Pregnancy termination (see paper on How I treat mismating in bitches and be scheduled 20 days later to assess the bitch for pregnancy. In case the queens) pregnancy is to go to term, the whelping date can be calculated 57±1 day from the first day of diestrus and confirmed by performing appropriate Uterine evacuation (including treatment of open cervix pyometra) in gestational measurements at the time of the pregnancy exam. bitches and queens References The mioconctracting action of PGF compounds is well known, and can become useful when dealing with cases of open-cervix pyometra or late • Fraser N, Wilborn R, Scultz W, Randall R, Pew C, Greer M. Comparative abortions with incomplete fetal expulsion. PGE compounds (see over) progesteroneassay. Clinical Theriogenology. 2015 7(3):207e10 are similary effective and characterized by less side effects. Dosage are the same as listed for pregnancy termination. We frequently use PGF • Hollinshead FK, Hanlon DW. Normal progesterone profiles during estrus compounds combined with aglepristone (see paper on How I treat mis- in the bitch: A prospective analysis of 1420 estrous cycles. Theriogenolo- mating in bitches and queens) as such combined treatments are shorter gy. 2019 Feb 1;125:37-42. and more efficacious. Care should be taken to make sure that the cervix is open, as inducing uterine contractions on a closed cervix may cause • Volkmann DH. The effects of storage time and temperature and uterine rupture or force uterine content up into the oviducts. Therefore, anticoagulant on laboratory measurements of canine blood progesterone aglepristone is administered first and then PGF or PGE (see over) are used concentrations. Theriogenology. 2006 Oct 1;66(6-7):1583-6. once cervical opening has occurred. Other clinical applications Prostaglandin F2a (PGF) products have been used also to induce parturi- tion (albeit with a continuous infusion pump) in 57-day pregnant bitches with whelping occurring normally within 2-3 days. A shortening of the interstrous interval may be obtained using PGF alone or in combination with antiprolactinics. The use of a 6-10 day course of PGF starting after day 10 of cytological diestrus will achieve a complete luteolysis which will shorten diestrus and often also anestrus. In male dogs, an increase in se- men volume and occasionally also quality (often motility) may be obtained by administration of PGF at the dose of 100 mcg/kg 15 minutes prior to semen collection; this has resulted in an increase of 270% of total sperm numbers when compared to saline treated controls, with no deleterious effect on refrigeration and freezing. PGF may also be used to obtain an ejaculate from a reluctant or inexperienced dog. Prostaglandin E1 - A synthetic analogue of Prostaglandin E1 (PGE), misoprostol, has a strong uterotonic action and may be used to help evac- uating uterine content in bitches and queens with pyometra. Misoprostol is marketed as a human compound under different trade names and is available in 200 mcg tablets. In the bitch it is administered at 10 mcg/kg BID orally (1/2 tablets/10 kg. It is very well tolerated and may be admin- istered at home by clients. It has no luteolytic properties and little if any side effects mostly on the first day of treatment (vomiting = 25% of cases; diarrhoea = 30% of cases). It can be used in both bitches and queens as an adjunct to a PGF2a or aglepristone treatment to improve uterine contractility, or to continue causing uterine contractions once luteolysis has been accomplished thus sparing the female the PGF2a related side effects. PGE pills may also be dissolved in saline solution and adminis- tered intravaginally. 232 WSAVA GLOBAL COMMUNITY CONGRESS

ANTIPROLACTINICS by increased GH mammary secretion, and is particularly evident in cats during treatment with MA. Endocrine side effects are transient and irrele- Prolactin is a major luteotrophic hormone and is important for canine vant when a young and healthy female receives a progestogen treatment and feline progesterone secretion from day 30 after ovulation onwards. with the right dosage and for an appropriate length of time. Unfortunately, Dopamine agonists like bromocriptine or cabergoline can directly reduce overdosing has occurred many times in the second half of last century prolactin secretion thereby suppressing progesterone levels. The sero- both in bitches and queens, and many of these cases have been report- tonin antagonist metergoline indirectly stimulates endogenous dopamine ed in the literature and cited over and again causing a widespread fear secretion and thus can inhibit prolactin secretion as well. Cabergoline about the use of these compounds. On the contrary, a large amount of has a slow clearance, which allows for a single oral daily administration. experimental data is available on the use of progestogens in bitches and Bromocryptine inhibits PRL secretion during relatively short periods of queens which dates back to when these animal species had to be used time (half-life: ± 4-6 hours) therefore it should be administered at least for approval of marketing of P4 compounds as human drugs in the ‘60s twice a day orally at doses 10-20 mcg/kg. Its lack of specificity leads to and ‘70s of last century. When reading the literature carefully it becomes side effects on the cardiorespiratory system, causing hypotension due to evident that all the case reports of pyometras, mammary nodules and vasodilatation (adrenergic type effect), or emesis whenever the dosage hypertrophy, diabetes, endocrine imbalances and many others were all exceeds 20 mcg/kg. Metergoline is essentially a serotoninergic antagonist due to a) the use of very high dosing, b) too long treatments, or c) choice with dopaminergic agonist properties when used orally at doses of 0.1-0.2 of the wrong candidate. For instance, treatment during diestrus should mg/kg BID. Its shorter half-life requires at least administrations twice a be avoided as it could easily cause overdosing even if the correct dosage day. Its antiserotoninergic properties may occasionally induce central is used; serum P4 assay may be useful to identify risk patients, and effects such as depression, nervousness, increased excitability, changes should be assayed also in queens due to a relevant incidence of sponta- in appetite (anorexia or bulimia), psychotic effects (escaping from home, neous ovulations in this species. Diabetic, pregnant or pseudopregnant rarely aggressiveness), rarely vomition. Antiprolactinic drugs can be used patients or females with a history of irregular cycling, vulvar discharge, in the bitch and the queen with three indications: pseudopregnancy, induc- mammary nodules or liver/kidney insufficiency should not be treated. tion of abortion and induction of estrus. Also, treatment during oestrus to suppress an unwanted heat should be done with caution and only with short-acting drugs for short periods of Pseudopregnancy time, as progestongens side effects are likely to be amplified by previous estrogen exposure. Table n° 1 shows the suggested dosages of the most Antiprolactinics are currently considered the treatment of choice for commonly used progestogen-based compounds in bitches and queens. pseudopregnancy. Their administration for 5-6 days at pharmacological The lowest effective dose should be used even if this may cause an earlier doses is effective in treating pseudopregnancy signs and reducing milk return to oestrus. Treatment durations of more than one year are probably production. Occasional failures can be dealt with by repeating the treat- adequate for young, healthy females, while shorter treatments should be ment protocol and extending it to 8-10 days, and also by associating the 2 considered for middle age females who may have subclinical uterine or drugs caberolne and metergoline mammary conditions. The use of progestogens in older females should be discouraged. Induction of abortion (see paper on How I treat mismating in bitches and queens) Estrus induction Suggested Bitch Queen Dosage The estrus inducing action of antiprolactinic drugs was initially thought to be due to the lowering of prolactin concentrations, but studies done at Megestrol Oestrus suppression <2.0 mg/ Oestrus postponement 0.02 Utrecht have demonstrated that shortening of anestrus occurs irrespec- Acetate kg for 8 days in proestrus to 0.09 mg/kg/day per os up tive of prolactin concentrations. Cabergoline and bromocriptine have to 1 year consistently given positive results, while metergoline’s results have been Oestrus postponement 0.05 more variable depending on dosage. Using low metergoline doses (0.1 to 0.01 mg/kg daily per os up mg/kg BID) from 100 days after ovulation until the following proestrus, the to 1 yr interoestrous interval will be significantly shortened. In our experience, the clinical use of cabergoline to induce oestrus has proven to be effective Oestrus postponement 1.5-2.0 in about 70-80% of cases. Occasionally a bitch may take more than 40- mg/kg SC or IM every 13 weeks 50 days of treatment which may cause the owner to get frustrated and discontinue the treatment. Medroxy-pro- 2.5-3.0 mg/kg SC or IM every Oestrus postponement 0.01- gesterone PROGESTOGENS Acetate 4-5 mos 0.05 mg/kg/day for up 1 year The mechanism of action of progestogens involves disruption of pitu- 0.05 mg/kg/day per os up to itary-ovarian communication resulting in lowered LH and FSH release and 1 year reduced concentrations of estrogen receptors in target tissues. Duration of effect depends on degree of pituitary responsiveness which increases Proligestone Oestrus postponement 10-33 Oestrus postponement 25-30 progressively during anestrus: therefore, early-mid anestrus treatments mg/kg SC every 3,4,5,5 months mg/kg SC every 5 months will be longer lasting than late anestrus treatments. Progestogens act on all target organs of P4 such as uterus (increased endometrial growth Table n° 1 – Suggested dosages of the 3 most commonly used progesto- and secretion), cervix (closure), motility of reproductive tract (decreased gen compounds in bitches for the control of reproduction. The dosage for gamete transport), mammary glands (stimulation of growth). Other proligestone in bitches should be intended 10 mg/kg in large size dogs hormones affected by a (short- or long-acting) progestogen treatments and up to 33 mg/kg in medium to small size dogs include, estrogens, inhibin and activin which may be decreased, growth hormone (GH) whose secretion by the mammary gland is increased, and prolactin which is inhibited during treatment and then shows a significant surge once treatment is discontinued. Insulin resistance is mediated 233

13–15 NOVEMBER, 2021 0159 Comparisons of the local control rates achieved with re-excision of the scar compared to radiation therapy of the scar suggest that the outcomes SOFT TISSUE SARCOMA & SURGERY, THE IDEAL of surgery, when possible, may be equivalent to those achieved with COMBI? adjunctive radiation therapy. In fact, when the costs and relative morbidity of radiation are factored in, an attempt at surgical excision alone may be N. Bacon a more desirable first line approach. The question then arises, what if the site of recurrence does not afford an extensive re-excision, or the owner Guildford/United Kingdom declines further treatment after a tumour positive margin is confirmed? Qualifications: Recent studies have evaluated the local recurrence rate of canine STS of the distal limbs treated by marginal excision alone (wait-and-see). Nicholas James Bacon Cavanaugh et al, 2007 followed 26 dogs with tumours of the distal ante- MA VetMB CertVR CertSAS DipECVS DACVS FRCVS brachium or pes, all of whom were determined to have tumour positive margins after marginal excision by a variety of surgeons, some planned, ACVS Founding Fellow (Surgical Oncology) some unplanned.All grades of STS were represented and follow-up inter- vals were long (median, 781 days, minimum 594 days).The rate of local RCVS Specialist in Small Animal Surgery (Surgical Oncology) recurrence was 37% (10/27 tumours) with only 12% (3/26) of the dogs being euthanized for problems relating to local disease. nickb@fitzpatrickreferrals.co.uk Soft tissue sarcoma (STS) is a catch-all classification referring to tumours Stefanello 2008 published a retrospective review of planned marginal that arise from the embryonic mesoderm and as such can occur anywhere excisions of low grade distal extremity soft tissue sarcomas by two expe- in the body. Surgical resection is the principal treatment for primary rienced surgeons. Using this technique, 32% surgeries has clean margins, localised disease as STS are relatively chemo-insensitive and radiotherapy 34% were ‘clean but close’ and 34% incomplete/dirty margins. Recurrence is more of value in a curative context as an adjunct to surgery. The great rate for this study was 11%. Follow up ranged from 210-2202 days. variation in anatomic location, factored with variable size and grade, can present significant problems when making a treatment plan. Chase et al, 2009 published the results of the removal of canine spindle cell tumours in first opinion practice (104 dogs). 53.8% of tumours were Surgical resection is the most effective treatment for STS. The aim of cu- on the limbs. 44% of all surgeries were marginal and the total rate of local rative-intent surgery is to widely excise the primary tumour (dogma; 3cm recurrence was 27.9%. Tumour location on the body was not significant- and/or a fascial plane) and achieve negative histopathological margins. ly related to survival or tumour recurrence. Those tumours that were The requirement for a 3cm margin to maximize local control of STS was palpably adherent to underlying tissues had a significantly worse DFI and challenged by Banks and Straw in 2004. In a prospective study, 14 dogs survival time. The tumours on the limbs were typically 1-5cm in diameter, with 15 subcutaneous STS were treated using a standardized protocol. fixed, marginally and incompletely excised, and the overall median survival A lateral surgical margin of > 10mm and a single fascial plane deep (or > time post surgery was 1040 days. 10mm of deep tissue) yielded a local disease control rate of 100% with a 93% one year disease-free interval. Radiation has a role if incomplete These studies seem to challenge the dogma that local recurrence rate margins are found, if further surgery is declined, or if the mass is close to following incomplete resection of STS is high, common, inevitable or guar- important unresectable structures. anteed, depending on your text source. As is the goal of any retrospective study, they raise questions rather than provide answers. The question This is a different situation in the distal limbs however (typically at/below which needs to be answered now is not HOW MANY recur, but what can the stifle, and at/below the elbow) where a wide surgical margin of skin is we do to predict WHICH are likely to recur. Ettinger and Scase have shown usually only achievable using free skin grafts or random flaps. Historically that AgNORs and possibly Ki67 could be used over and above grade to options such as amputation or marginal resection and radiation have been help predict overall survival in STS, and for a starter, this work needs to considered considered. Both these options have drawbacks in terms of be repeated in the context of local recurrence with a similar population altered function, morbidity and cost. Whereas it is expected amputation to of dogs with similar wounds in terms of tumour burden. McSporran in treat an extremity sarcoma will effect a local cure, marginal or incomplete 2009 demonstrated in 139 tumours that local recurrence rates between excision of a STS plus adjunctive curative-intent (hypofractionated) radia- different grades differed significantly with grade 1 and 2, and 1 and 3 tion results in a local recurrence rate of 19-35%. both differing significantly. Clean margins predicted nonrecurrence, NOT marginal versus wide. Interestingly actual survival was not impacted by A recent study reported the results of intentional marginal excision of tumour recurrence. canine soft tissue sarcomas, followed by a coarsely fractionated radiation protocol (once weekly 8-9Gy x 4weeks) (Demetriou et al, JSAP 2012). 39 A ‘palliative’ four fraction radiation therapy alone has also been used to dogs in the study had distal tumours (out of a total of 56) and these dogs treat macroscopic soft tissue sarcomas in 16 dogs (Lawrence et al, 2008). did not have a statistically significant different disease free interval with Dogs received 8Gy x 4 (days 0,7,14,21). 7 tumours were on limbs and 4/7 this therapeutic protocol compared to more proximally located tumours had a partial response (greater than 50% reduction in tumour volume) or tumours on the flank. A local recurrence rate of 18% was seen across and 3/7 had stable disease (less than 50% reduction and less than 25% all tumours in all locations, with a further 9% having metastasis with or growth). The median progression free interval for all dogs in all anatomic without local recurrence. sites was 155 days. In all dogs, 75% were alive at 6 months and 37% alive at 12 months. It was suggested this protocol is suitable for cases where Retrospective investigation into the results of surgery alone (‘primary definitive treatment (surgery with/without curative RT) is not elected or is re-excision’) for the treatment of STS after incomplete resection studied not expected to improve local control. 41 dogs that had undergone aggressive scar revision (attempted wide margins (1-3cm)/1 fascial plane deep) for incompletely excised STS. A palliative three fraction cobalt protocol (8Gyx3, one weekly) was Complete margins were obtained after re-excision in 90% (37/41) of all reported in 15 dogs with non-resectable soft tissue sarcomas, 10 of which the cases with mean margin widths of 2.7cm on the proximal portion of had tumours on the extremities. In all 15 patients, stable disease was limbs and 1.4cm on the distal portion of limbs. Local tumour recurrence achieved in 87%, with median time to progression and survival being 263 occurred in 15% (6/39) of the dogs at a median time to recurrence of 142 and 332 days respectively. days. 234 WSAVA GLOBAL COMMUNITY CONGRESS

In both human and veterinary surgical oncology, accepted guidelines on 0160 treatment of solid tumours have been difficult to establish. A large stum- bling block in creating guidelines on treatment of STS is the uncertainty EVIDENCE BASED ADJUNCTIVE MANAGEMENT OF over what to do with an incomplete surgical margin and its relevance CANINE SOFT TISSUE SARCOMAS on local recurrence and overall survival. The impact of leaving residual P. Clemente-Vicario tumour cells in the wound bed of an excised STS is a many fold increase in the rate of local recurrence (Kuntz, McSporran) but the relationship Calpe/Spain between local recurrence and overall survival remains unclear. Future directions and treatments?? Qualifications: It would be ideal to identify those at risk of local recurrence or metastasis Pachi Clemente-Vicario BEFORE surgery based on imaging and better predicting biological be- haviour. We could then tailor the dose of surgery and treatment accord- DVM, MSc, Diplomate ACVIM (Oncology) ingly taking into account the animal’s age, status and prognosis. If we follow human advances, then intra-arterial chemotherapy, interventional pachi@lamerced.net chemo-embolisation or isolated limb-perfusion (melphalan/TNFµ) are also Mesenchymal tumors include those arising from the supporting mesen- treatments that may be considered in the future. chymal tissues of the dermis and subcutis as fibrous connective tissue, blood vessels, lymphatics, nerves, adipose tissue and smooth muscle1. The bigger picture here is that STS in humans are relatively uncommon, All these tumors are called soft tissue sarcomas (STS) and locally infiltra- accounting for <1% of all cancers, with 8500 new cases being diagnosed tive, have a propensity to have pseudocapsule and have low metastatic a year in the US, and 13000 in the EU. Although relatively rare in the dog, potential. Some of the STS may behave in a different pattern depending STS are seen commonly in secondary and tertiary referral practices. on the location, with an expansile growth in in distal limbs and infiltrative Scope for translational (what would be called pre-clinical trials in the growth with satellite nodules in other sites2. human setting) exists and is likely to benefit both parties. Up to 11% of cases may have metastasis at diagnosis, being as well relat- ed with the histological grade of malignancy: 6% of all the grade I cases, 6% of all the grade II cases and 38% of the grade III cases have pulmonary nodules at presentation3. One study found up to 23% of cases of soft tissue sarcoma to have pulmonary nodules4. Soft tissue sarcomas are more common in the legs, with approximately 50-60% of cases, followed by the trunk (30-35%), and head and neck (4- 12%). Low grade tumors are more common with 50-66% of cases being grade I, 27-42% grade II and 6-7% grade III5,6. Surgery When treated in first opinion practice, many cases go to surgery without a previous diagnosis and resected with conservative surgeries. Despite the lack of an aggressive surgery, recurrence rate after surgery by general practitioners is 20-28% but is dependent on grade and completeness of surgical margins. The recurrence rate is 7% for grade I, 34% for grade II and up to 75% in grade III) and the disease free interval is usually more then 12 months5-7. Complete resection of the tumor is associated with lower risk of recurrence -or no recurrence in some studies2- and the risk increases for less aggressive surgeries with a cumulative risk at three years after surgery of 42% for infiltrated margins, 23% for “Clean but close” and 7% for clean margins8. Size and depth are associated with increased risk of relapse2. Radiation therapy Due to the risk of local recurrence, radiation therapy has been investigated as adjuvant therapy of soft tissue sarcomas. Definitive protocols given postoperatively (42 to 57 Gy given in 3 to 4.2 fractions) were administered to 35 dogs, eleven of which developed local recurrence (31%) with median time to recurrence greater than 800 days. 14% of cases developed distant metastases9. Hypofractionated protocols (4-5 weekly fractions of 6 to 8 Gy) for microscopic soft tissue sarcoma was administered to 48 dogs. 21% developed local recurrence at a median time of 276 days. Progres- sion free survival was associated with tumor grade, being longer for grade I (1904 d) than for grade III (292). 23% of cases developed metastases that was more common in grade II and III10. Definitive protocols (16 to 25 daily fractions) in incompletely excised high grade tumors was associated to development of local recurrence in 20% of cases and 23% developed metastases11. 235

13–15 NOVEMBER, 2021 Chemotherapy • Chase D, Bray J, Ide A, Polton G. Outcome following removal of canine spindle cell tumours in first opinion practice: 104 cases. J Small Anim Only a few studies have been published investigating the role of adjuvant Pract. 2009 Nov;50(11):568-74. chemotherapy in the management of soft tissue sarcomas. Only 7 out of 167 dogs with hemangiopericytomas were treated with chemotherapy af- • Chiti LE, Ferrari R, Roccabianca P, Boracchi P, Godizzi F, Busca GA, Ste- ter surgery, with no difference in the recurrence rate compared with cases fanello D. Surgical Margins in Canine Cutaneous Soft-Tissue Sarcomas: A treated only surgically12. Crownshaw et al did not find a benefit adding Dichotomous Classification System Does Not Accurately Predict the Risk chemotherapy to the radiation therapy protocol11. of Local Recurrence. Animals (Basel). 2021 Aug 11;11(8):2367. Another local approach that has been investigated is the placement of • Forrest LJ, Chun R, Adams WM, Cooley AJ, Vail DM. Postoperative intralesional cisplatin-impregnated beads after marginal surgery. A study radiotherapy for canine soft tissue sarcoma. J Vet Intern Med. 2000 Nov- with 51 cases found that toxicity was common (47%) and recurrence was Dec;14(6):578-82. 29%, having better disease free intervals in grades I and II, and only 148 days for grade III13. A similar study found common wound complications • Kung MBJ, Poirier VJ, Dennis MM, Vail DM, Straw RC. Hypofractionated (84% of cases) and recurrence in 16% of dogs14. radiation therapy for the treatment of microscopic canine soft tissue sarcoma. Vet Comp Oncol. 2016 Dec;14(4):e135-e145. Metronomic chemotherapy reported a 20% recurrence rate (similar to oth- er studies that used no adjuvant therapy) with a 40% toxicity15. Potential mechanism of action of the metronomic chemotherapy include modula- tion of immune system and antiangiogenesis15. Electrochemotherapy combines the administration of anticancer drugs with the delivery of electric pulses that increase the drug uptake through the cell membranes. 30 dogs with incompletely excised STS were treated with electrochemotherapy using bleomycin IV and cisplatin injected under the surgical scar. Treatment was repeated after two weeks, with a result of 13% recurrence rate, and an estimated disease free interval of 857 days17. In another study with 50 cases, 26 were treated with intra-op- erative electrochemotherapy and 24 cases were treated with adjuvant ECT. Recurrence rates and DFI were 23% at 81 days and 25% at 243 days respectively18. Some of the cases that recurred were treated a second time, but over 90% of cases received only one treatment. Most of references of this review are retrospective case series, of low level of evidence (4). Similar findings are shown in a paper by Ann Hohen- haus et al that uses evidence base medicine to make treatment recom- mendations in a case of STS19. In summary, soft tissues sarcomas are common in small animal practice. Approximately one out of four will develop local recurrence (more likely with incomplete margins and/or high grade) and one out of ten may devel- op metastasis (higher risk with higher grade). Although with some adju- vant therapies, the disease free interval can be prolonged, the recurrence rate does not change substantially and new therapies are needed. References • Ehrhart N. Soft-tissue sarcomas in dogs: a review. J Am Anim Hosp Assoc. 2005 Jul-Aug;41(4):241-6. • Avallone G, Boracchi P, Stefanello D, Ferrari R, Rebughini A, Roccabianca P. Canine perivascular wall tumors: high prognostic impact of site, depth, and completeness of margins. Vet Pathol. 2014 Jul;51(4):713-21. • Villedieu EJ, Petite AF, Godolphin JD, Bacon NJ. Prevalence of pul- monary nodules suggestive of metastasis at presentation in dogs with cutaneous or subcutaneous soft tissue sarcoma. J Am Vet Med Assoc. 2021 Jan 15;258(2):179-185. • Lamb CR, Whitlock J, Foster-Yeow ATL. Prevalence of pulmonary nodules in dogs with malignant neoplasia as determined by CT. Vet Radiol Ultrasound. 2019 May;60(3):300-305. • Bray JP, Polton GA, McSporran KD, Bridges J, Whitbread TM. Canine soft tissue sarcoma managed in first opinion practice: outcome in 350 cases. Vet Surg. 2014 Oct;43(7):774-82. • McSporran KD. Histologic grade predicts recurrence for marginally excised canine subcutaneous soft tissue sarcomas. Vet Pathol. 2009 Sep;46(5):928-33. 236 WSAVA GLOBAL COMMUNITY CONGRESS

0161 - Periodontal disease HOW TO MANAGE DENTAL PROBLEMS IN RABBITS - Odontogenic abscesses - DRAFT OF DENTAL GUIDELINES - Soft tissue pathology V. Jekl - Oral tumours Brno/Czech Republic Section 4: Anaesthesia and Pain management Qualifications: - Local anaesthesia Vladimir Jekl - General anaesthesia Associate Professor, MVDr., Ph.D., DipECZM (Small Mammal) How to manage dental problems in Rabbits - Draft of dental guidelines - Pain management Assoc. Prof., MVDr. Vladimir Jekl, Ph.D., DipECZM1,2 Section 5: Necessary Equipment 1Jekl & Hauptman Veterinary Clinic – Focused on Exotic Companion Section 6: Oral Examination and Recording Mammal Care, Mojmirovo namesti 3105/6a, 61200 Brno, 2Department of Pharmacology and Pharmacy, Faculty of Veterinary Medicine, University Section 7: Diagnostic imaging of dental disease of Veterinary and Pharmaceutical Sciences Brno, Palackeho trida 1, 61242 Brno, Czech Republic - Endoscopy Rabbits are commonly kept as pet animals in Europe, USA and throughout - Radiography the world. Oral cavity diseases are the most frequently reported diseases in privately kept small herbivorous mammals. In rabbits, guinea pigs, - Computed tomography chinchillas and degus a wide range of local and systemic conditions which affect the mouth and oral cavity have been described: hereditary, Section 8: Dental extractions infectious, metabolic, lack of chewing, lack of diet abrasive properties, traumatic (foreign bodies included), and neoplasm. With increasing popu- - Incisor extraction larity, the complexity of diagnostic and surgical procedures performed in rabbits is increasing. - Intraoral premolar and molar extraction In dogs and cats, “World Small Animal Veterinary Association Global - Apicoectomy Dental Guidelines” was published as the guidelines to assist practitioners from around the world. Their purpose is to guide the general practitioner Section 9: Odontogenic abscesses management towards successful detection, diagnosis and therapy of the most common oral and dental conditions. While continued research is required in all Section 10: Antibiotic treatment of dental disease, if indicated areas represented in these guidelines, a distinct effort has been made to provide peer reviewed, evidence-based, recommendations in all areas. Section 11: Animal Welfare issues concerning dental health The similar guidelines are under development also for exotic companion mammals. This article shows a summary of the draft of dental guidelines References for pet rabbits. - more references on request The emphasis is given on diagnostics as exact pathological process/ lesion or processes/lesions identification together with general clinical • Artiles CA, Sanchez-Migallon Guzman D, Beaufrère H, Phillips KL. examination can only lead to proper therapeutic protocol and prognosis Computed tomographic findings of dental disease in domestic rabbits establishment. This knowledge is of great importance also for further (Oryctolagus cuniculus): 100 cases (2009-2017). J Am Vet Med Assoc. client treatment plan discussion. 2020;257(3):313-327. Each section contains an extensive reference list should the practitioner • Boehmer E, Crossley D. Objective interpretation of dental disease in require additional information. rabbits, guinea pigs and chinchillas. Tierärztl Prax 2009;37(K):250–260 The sections include: • Bohmer, E. Dentistry in Rabbits and Rodents. Oxford: Wiley-Blackwell, 2015 Section 1: Species definition • Capello V. Diagnostic Imaging of Dental Disease in Pet Rabbits and - European rabbit (Oryctolagus cuniculus) Rodents. Vet Clin North Am Exot Anim Pract. 2016;19(3):757-82 Section 2: Oral anatomy • Capello V. Surgical Treatment of Facial Abscesses and Facial Surgery in Pet Rabbits. Vet Clin North Am Exot Anim Pract, 2016;19(3):799-823. - Oral and dental anatomy and physiology • Jekl V, Redrobe S. Rabbit dental disease and calcium metabolism--the Section 3: Pathophysiology of dental disease science behind divided opinions. J Small Anim Pract. 2013;54(9):481-90 Section 3: Dental and soft tissue pathologies • Jekl V. Radiography in pet rabbits, ferrets, and rodents. In: Niemec BA, Gawor J., Jekl V. Practical Veterinary Radiography. CCR Press, USA, 2017, - Incisor pathology pp 271-346 - Premolar and molar pathology • Niemiec B, Gawor J, Nemec A, Clarke D, McLeod K, Tutt C, Gioso M, Steagall PV, Chandler M, Morgenegg G, Jouppi R, McLeod K. World Small Animal Veterinary Association Global Dental Guidelines. J Small Anim Pract. 2020 Jul;61(7):395-403. • Regalado A, Legendre L. Full-Mouth Intraoral Radiographic Survey in Rabbits. J Vet Dent. 2017;34(3):190-200. 237

13–15 NOVEMBER, 2021 • Summa NM, Brandão J. Evidence-Based Advances in Rabbit Medicine. 0162 Vet Clin North Am Exot Anim Pract. 2017;20(3):749-771 HOW TO MANAGE DENTAL PROBLEMS IN CHINCHILLAS - DRAFT OF DENTAL GUIDELINES V. Jekl Brno/Czech Republic Figure 1: Comparison of a lateral rostro-caudal radiograph and oblique Qualifications: sagittal view of the same rabbit with odontogenic abscess located caudal to right mandibula M2 (410) – arrows. Last molar (411) is missing and Vladimir Jekl clinical and the clinical and reserve crown M2 (410) is partially lytic from its distal surface. Note also irregular (different clinical crown high) occlu- Associate Professor, MVDr., Ph.D., DipECZM (Small Mammal) sal premolar and molar surface and apical premolar and molar elongation How to manage dental problems in Chinchillas (Image courtesy of Vladimir Jekl) - Draft of dental guidelines - Assoc. Prof., MVDr. Vladimir Jekl, Ph.D., DipECZM1,2 1Jekl & Hauptman Veterinary Clinic – Focused on Exotic Companion Mammal Care, Mojmirovo namesti 3105/6a, 61200 Brno, 2Department of Pharmacology and Pharmacy, Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences Brno, Palackeho trida 1, 61242 Brno, Czech Republic Dental disorders are commonly diagnosed in pet chinchillas as it is in other small herbivorous mammals with complete elodont (continuously growing) dentition, such are rabbits, guinea pigs and degus. However, subclinical dental disease has been detected in 35% of clinically healthy chinchillas examined, therefore subclinical dental abnormalities should not be always assumed to be responsible for clinical signs and symptoms such as anorexia.1 Older chinchillas are more likely to be diagnosed with dental disease. In comparison to rabbits, lower incidence of odontogenic abscesses and high incidence of periodontal disease, caries, and tooth resorption are reported. In chinchillas, incisor hypoplasia and gingival hyperplasia is also very commonly seen as one of the associate pathologies with dental disease. As many dental disorders are not detected, a thorough oral cavity examination and dental/skull radiology and/or computed tomography is recommended to exactly show pathological lesions. In dogs and cats, “World Small Animal Veterinary Association Global Dental Guidelines” was published as the guidelines to assist practitioners from around the world. Their purpose is to guide the general practitioner towards successful detection, diagnosis and therapy of the most common oral and dental conditions. While continued research is required in all areas represented in these guidelines, a distinct effort has been made to provide peer reviewed, evidence-based, recommendations in all areas. The similar guidelines are under development also for exotic companion mammals. This article shows a summary of the draft of dental guidelines for pet chinchillas. The sections include: Section 1: Species definition - chinchilla (Chinchilla lanigera) Section 2: Oral anatomy - Oral and dental anatomy and physiology Section 3: Pathophysiology of dental disease Section 3: Dental and soft tissue pathologies (Figure 1) - Incisor pathology 238 WSAVA GLOBAL COMMUNITY CONGRESS

- Premolar and molar pathology • Niemiec B, Gawor J, Nemec A, Clarke D, McLeod K, Tutt C, Gioso M, - Periodontal disease Steagall PV, Chandler M, Morgenegg G, Jouppi R, McLeod K. World Small - Dental caries Animal Veterinary Association Global Dental Guidelines. J Small Anim - Odontogenic abscesses Pract. 2020 Jul;61(7):395-403. - Soft tissue pathology Figure 1: Oral cavity endoscopy images of a female  - Oral tumours Section 4: Anaesthesia and Pain management chinchilla affected with parodontitis and secondary odontogenic abscess - Local anaesthesia (A-D). A – examination immediately after the right maxillary premolar - General anaesthesia (108) and molar (109) extraction with parodontal probe in place, where the - Pain management fistulation to the soft tissue was present; B-D – recheck in day 7, day 20 Section 5: Necessary Equipment and day 40 after the extraction. D - Note healed gingiva mesial to the M2 Section 6: Oral Examination and Recording (110) (Image courtesy of Vladimir Jekl) Section 7: Diagnostic imaging of dental disease - Endoscopy - Radiography - Computed tomography Section 8: Dental extractions - Incisor extraction - Intraoral premolar and molar extraction Section 9: Odontogenic abscesses management Section 10: Antibiotic treatment of dental disease, if indicated Section 11: Animal Welfare issues concerning dental health References - more references on request • Boehmer E, Crossley D. Objective interpretation of dental disease in rabbits, guinea pigs and chinchillas. Tierärztl Prax 2009;37(K):250–260 • Bohmer, E. Dentistry in Rabbits and Rodents. Oxford: Wiley-Blackwell, 2015 • Brenner S.Z.G., Hawkins M.G., Tell L.A., Hornof W.J., Plopper C.G., Verstraete F.J.M. Clinical anatomy, radiography, and computed tomogra- phy of the chinchilla skull. Compendium on Continuing Education for the Practicing Veterinarian 2005;27(12):933-942. • Capello V. Diagnostic Imaging of Dental Disease in Pet Rabbits and Rodents. Vet Clin North Am Exot Anim Pract. 2016;19(3):757-82 • Crossley DA. Dental disease in chinchillas in the UK. J Small Anim Pract. 2001 Jan;42(1):12-9. • Jekl V, Hauptman K, Knotek Z. Quantitative and qualitative assess- ments of intraoral lesions in 180 small herbivorous mammals. Vet Rec. 2008;162(14):442-9 • Jekl V. Radiography in pet rabbits, ferrets, and rodents. In: Niemec BA, Gawor J., Jekl V. Practical Veterinary Radiography. CCR Press, USA, 2017, pp 271-346 • Legendre LF. Malocclusions in guinea pigs, chinchillas and rabbits. Can Vet J. 2002;43(5):385-90. • Mans C, Jekl V. Anatomy and Disorders of the Oral Cavity of Chinchillas and Degus. Vet Clin North Am Exot Anim Pract. 2016;19(3):843-69. 239

13–15 NOVEMBER, 2021 0163 Common causes MASTERING DRY EYE DISEASE- A SYSTEM FOR Immune-mediated constitutes to a large percentage of cases with some breeds CLINICAL SUCCESS KCS being disproportionally affected suggesting a genetic pre- M.-C. Fischer disposition. Patients usually respond well to treatment with topical CsA. Hatfield/United Kingdom Infectious KCS distemper virus (dogs), feline herpesvirus (FHV-1), leishmania infection or any chronic bacterial or viral conjunctivitis. The Qualifications: tear production may improve once the primary infection has Maria-Christine Fischer resolved. Dr.med.vet. DipECVO PGCertVetEd MRCVS Surgically induced can occur after excision of a prolapsed third eyelid gland (2) KCS and evisceration/ prosthesis (3). mfischer@rvc.ac.uk Drug induced KCS Most common toxic agents are sulfur drugs. Up to 50% of dogs develop KCS within 7-30 days of starting the drug MASTERING DRY EYE- A SYSTEM FOR CLINICAL SUCCESS and animals weighing less than 12kg may be at increased risk. The adverse effects of sulfur drugs on lacrimation Dry eye disease (keratoconjunctivitis sicca/KCS) is one of the most com- can be transient with short duration of administration (4). mon ocular diseases in dogs and frequently undiagnosed. We will discuss Topical/ systemic atropine as well as general anaesthesia symptoms that raise suspicion for KCS. Although it is a chronic disease and sedation (effect 24 hours, but prolonged when duration with an inflammatory vicious cycle, a strategic approach frequently leads longer than 2 hours) can lead to a temporarily reduced tear to a good treatment response and clinical improvement of affected production. patients. Systemic diseases KCS may be associated with metabolic diseases such as How do I recognize dry eye patients? hypothyroidism, diabetes mellitus and Cushing’s disease. Severe KCS occurs together with dilated pupils, protrusion of Clinical signs are the initial alert that a tear film disorder is present. The the third eyelid, ptosis and systemic signs with dysautonomia classical signs are mucoid or mucopurulent discharge (aqueous deficien- (Key- Gaskell Syndrome). For dysautonomia cases artificial cy), epiphora (mucin/ lipid deficiency), conjunctivitis, ocular discomfort, tears and anticholinergic drugs (pilocarpine) should be used. keratitis with corneal vascularisation and pigmentation, non-/ slow-healing corneal ulcers, blepharitis (primary meibomitis resulting in lipid deficiency Neoplasia Neoplasia of the lacrimal glands is rare, but KCS can be or secondary with periocular dermatitis due to accumulation of periocular associated with orbital disease (inflammatory or neoplastic). discharge), visual deficits (with chronic keratitis), and an ipsilateral dry Exophthalmos, strabismus and altered globe retropulsion can nostril with neurogenic KCS due to impaired innervations of the lateral raise suspicion and should prompt orbital imaging. Irradiation nasal gland and the lacrimal glands. of head neoplasia can damage the lacrimal and nictitans gland. How do I diagnose dry eye disease? Congenital acrinar Unilateral absent tear production, unlikely to respond to CsA, hypoplasia usually requires parotid duct transposition. Orbital or supraorbital trauma and proptosis of the globe can cause disruption of the blood supply and innervation of the lacrimal gland. Injury to the facial nerve (particularly with Traumatic & neuro- middle ear disease) can lead to neurogenic dry eye. Concur- genic KCS rent xeromycteria of the ipsilateral nostril strongly suggests neurogenic dysfunction. Impaired blinking due to facial nerve paralysis/paresis and/or dysfunction of the sensory trigemi- nal nerve can exacerbate KCS. How do I manage dry eye patients? 2. Improve tear distribution, prevent loss of tears and improve comfort: 1. Determine the underlying cause; Careful assessment of the history, Affected patients benefit from correction of ectropion or entropion, remov- clinical signs, and thorough diagnostic testing will facilitate recognition of al of distichiasis and/ or reduction of the palpebral fissure. the underlying cause and selection of appropriate treatment. 3. Stimulate the natural tear production - Cyclosporine A (CsA). This calcineurin inhibitor remains the cornerstone of KCS treatment due to its immune-modulatory (5) and tear stimulating properties. Dogs with STT values of 0-1mm/min have an approximately 50% chance of improving and dogs with STT values of over 2mm/min have an 80% chance (6). Improvement is evident as decreased mucopu- rulent discharge, corneal vascularisation and pigmentation and occurs in most patients, even in dogs whose tear production does not increase. The recommended regime is topical, long-term application every 12 hours. Its maximal effect is reached after 60-90 days. Incorporative patients benefit from an episcleral CsA implant. The effect lasted over one year (7). CsA is ineffective in neurogenic KCS, drug-induced and congenital acrinar hypoplasia. 240 WSAVA GLOBAL COMMUNITY CONGRESS

- Tacrolimus. This calineurin inhibitor operates via a different cellular re- people. Cases with granulomatous blepharitis secondary to ruptured ceptor than CsA and appears to be more potent. It increases tear produc- meibomian gland benefit from additional systemic corticosteroids. Warm tion and improves clinical signs in dogs, including some animals that were eyelid compresses 2-3 x daily can support secretion from the inspissated nonresponsive to topical CsA treatment (8). Its potential carcinogenicity meibomian glands. requires further studies and as use for KCS in dogs is off-label, CsA 0.2% ophthalmic ointment should remain the first-line treatment, with tacrolim- - Mucin-deficient KCS responds to treatment with CsA, which restores the us reserved for cases unresponsive to CsA. of conjunctival goblet cell mucin production independent of the lacrimo- genic effect. - Pilocarpine. This cholinergic agent can be administered in cases with neurogenic KCS to provide parasympathetic stimulation of the lacrimal References gland (9). Ophthalmic preparation of 2% pilocarpine can be added to the patient’s food (1 drop twice daily for 10kg and increase the dose in 1 drop 1. Giuliano EA. Diseases and Surgery of the Canine Lacrimal Secretory increments every 2-3 days until tearing or systemic side effects (inappe- System. In: Gelatt KN, editor. Veterinary Ophthalmology. 6th ed. Wiley tence, hypersalivation, vomiting, diarrhea, bradycardia) develop). Blackwell; 2021. p. 1008–44. 4. Supplement tears depending on which component (aqueous, mucin, 2. White C, Brennan ML. veterinary sciences An Evidence-Based Rapid Re- lipid) is insufficient view of Surgical Techniques for Correction of Prolapsed Nictitans Glands in Dogs. Vet Sci. 2018;5(75):442–52. Unfortunately, there is no ideal product that adequately replaces all func- tions served by the tears. Following properties should be considered when 3. Blocker T, Hoffman A, Schaeffer DJ, Wallin JA, Blocker T. Corneal sen- choosing lacromimetics: sitivity and aqueous tear production in dogs undergoing evisceration with intraocular prosthesis placement. Vet Ophthalmol. 2007;10(3):147–54. - Viscosity: High viscosity agents cause blurry vision but provide pro- longed comfort. 4. Miller P. Lacrimal System. In: Maggs D, Miller P, Ofri R, editors. Slatter’s Fundamentals of Veterinary Ophthalmology. 5th ed. St. Louis: Elsevier - pH: The canine tear film pH is 8 (10). A mismatch between patient and Saunders; 2013. p. 165–84. artificial tear pH can cause irritation upon instillation. 5. Sussadee M, Rucksaken R, Havanapan PO, Reamtong O, Thayanan- - Osmolarity: As dry eye is a hyperosmolar stare, hyposmolar drops are uphat A. Changes in tear protein profile in dogs with keratoconjunctivi- preferrable. tis sicca following topical treatment using cyclosporine A. Vet World. 2021;14(6):1711–7. - Preservatives prevent contamination and bacterial growth, but have dose dependent, deleterious ocular effects (tear film instability, goblet 6. Kaswan RL, Salisbury MA. A new perspective on canine keratoconjunc- cell loss, epithelial apoptosis, squamous metaplasia, subconjunctival tivitis sicca: Treatment with ophthalmic cyclosporine. Vet Clin North Am fibrosis, hypersensitivity). High-security, high-technology bottles without - Small Anim Pract. 1990;20(3):583–613. preservatives are available. They dispense the drops through a filter which prevents microbial contamination. 7. Barachetti L, Rampazzo A, Mortellaro CM, Scevola S, Gilger BC. Use of episcleral cyclosporine implants in dogs with keratoconjunctivitis sicca: Hyaluronate demonstrates numerous desirable properties (high viscosity, Pilot study. Vet Ophthalmol. 2015;18(3):234–41. water retentive properties, localized anti-inflammatory activity, improved cellular migration/ healing, CD44 adhesion molecule inactivation) and 8. Berdoulay A, English R V, Nadelstein B. Effect of topical 0.02 % tacrolim- products without preservatives are available. Lipid based artificial tears us aqueous suspension on tear production in dogs with keratoconjunctivi- should be used for treatment of evaporative dry eye and meibomian gland tis sicca. Vet Ophthalmol. 2005;8(4):225–32. dysfunction. Autologous serum is similar to tears in many ways and has shown to improve e.g. tear film breakup times and pain scores. Its han- 9. Klauss G, Constantinescu GM. Nonhypotensive autonomic agents dling remains challenging, and we are awaiting more rigorous controlled in veterinary ophthalmology. Vet Clin North Am - Small Anim Pract. studies on its clinical efficacy. 2004;34(3):777–800. 5. Reduce ocular surface inflammation 10. Beckwith-Cohen B, Elad D, Bdolah-Abram T, Ofri R. Comparison of tear pH in dogs, horses, and cattle. Am J Vet Res. 2014;75(5):494–9. CsA and Tacrolimus have anti- inflammatory properties. CsA appears to be safe to use with corneal ulceration as it does not alter the ocular surface flora. Additional corticosteroids should ideally be avoided as KCS patients are prone to ulceration and corticosteroids will complicate corneal heal- ing. They should only be used with extreme caution. 6. Control secondary infection Mucopurulent discharge does not necessarily indicate secondary bacterial infection, as neutrophiles are present as a result of the inflammation occuring with KCS. Conjunctival cytology is useful to determine whether the discharge is sterile or septic. In general, long-term topical antibiotics are not required and their continuous application only results in irritation and resistant microorganisms. 7. Special consideration for qualitative tear film deficiency - Lipid tear film disorders: Opportunistic or pathogenic bacterial infection of the meibomian glands should be treated with systemic and topical antibiotics after culture and sensitivity from expressed meibum. Oral tetracyclines and omega-3 fatty acids are commonly recommended in 241

13–15 NOVEMBER, 2021 0164 abnormalities such as entropion, ectropion, trichiasis, distichiasis, ectopic cilia, as well as eyelid function resulting in lagophthalmos, neuroparalytic CORNEAL ULCER- WHAT TO DO WHEN IT WON’T keratitis. Further the position and size of the globe, tear film quantity and HEAL quality, innervation of the cornea must be evaluated. Corneal endothelial M.-C. Fischer dystrophy or degeneration, immune-mediated keratitis, stromal calcific degeneration, corneal sequestra in cats and foreign bodies should be Hatfield/United Kingdom ruled out. Qualifications: • Infection Maria-Christine Fischer A bacterial infection typically results in stromal involvement or loss. A Dr. med. vet. Dip ECVO MRCVS whitish or yellow infiltrate suggests the presence of inflammatory cells. European Specialist in Veterinary Ophthalmology The cornea may become malacic (gelatinous). Fungal infections are typ- ically more painful, vascularize only slowly, are usually heavily infiltrated. Lecturer in Ophthalmology Surrounding satellite lesion may be present. Feline herpes virus typically results in superficial, dendritic lesions at first, that become geographic. mfischer@rvc.ac.uk Some cats develop a chronic, superficial ulcers with nonadherent epitheli- um that looks like an indolent ulcer in a dog. CORNAL ULCER- WHAT TO DO WHEN IT WON’T HEAL Corneal ulcers that heal abnormally slow are frequently a reason for refer- • Superficial chronic corneal epithelial defect (SCEED) ral and can be very frustrating for both the client and the veterinarian. This session is intended to aid the veterinarian in identifying complications in A SCCED is characterized as an uninfected, superficial ulcer without stro- corneal wounds healing and in strategically diagnosing the cause of delay. mal loss and with a lip of non-adherent corneal epithelium. This syndrome It also informs about available treatment options which can be used in is typically present in elderly dogs and occurs secondary to formation of addition to standard therapy. an abnormal superficial stromal hyaline acellular zone that interferes with the normal corneal healing. To start with, it is essential to understand normal corneal wound healing. This is especially helpful to manage expectations and identify complica- The following methodical methodical work up will help you to assign the tions in the corneal wound healing. ulcer to one of the three categories: BASICS OF CORNEAL WOUND HEALING (1) ULCER TREATMENT Epithelial defects heal by epithelial sliding and mitosis. The limbus is the Most important for supporting corneal wound healing is to identify and source of epithelial stem cells. The entire cornea can re-epithelialise with- remove or treat the underlying cause. in 4-7 days. The anchoring fibrils and hemidesmosomal attachments to the basement membrane will however take longer to form and if the basal ● Standard medical therapy lamina has been damaged this can take weeks to months. During this time the epithelium can easily be removed. Standard medical therapy for corneal ulcers includes topical use of antimi- crobials to treat or prevent bacterial infections. Cytology and culture and Stromal healing takes longer and depends on the depth and size of the sensitivity are essential to choose the appropriate anitbiotic. Systemic defect. Uncomplicated and complicated stromal wound healing can be administration of nonsteroidal anti-inflammatory drugs (NSAIDs) is often distinguished. Uncomplicated stromal wounds heal without vascularisa- indicated to reduce pain and potential corneal white blood cell infiltration. tion. Keratocytes transform into fibroblasts, which synthesize collagen They can however reduce the rate of corneal vascularisation. Cycloplegic and extracellular matrix components. Complicated, deeper and more agents are used to address ocular pain associated with reflex uveitis. extensive stromal injuries heal with additional vascularisation. Fibro- Topical corticosteroids are contraindicated unless used for treatment vascular ‘granulation tissue’ fills up the defect and eventually regresses. of immunemediated keratitis. They predispose for infection and corneal Although the disorganized arrangement of the new collagen fibres results melting, and delay corneal healing. Topical NSAIDs may also delay corneal in scar tissue formation and opacities, corneal clarity can improve while healing. Complicated stromal ulcers can benefit from a loading dose and the stroma remodels over a period of 3-6 months. Corneal melting or kera- require frequent topical medication (often every 1-2 hours). We therefore tomalacia can develop, when the balance between collagenolytic enzymes recommend hospitalisation in the intial phase. and proteinase inhibitors, both required for physiological wound healing and remodelling, is disturbed. Damage to the endothelial cells is irreversible as these cells are postmi- totic and heal mainly by endothelial sliding. If the pump function of the remaining endothelial cells is overwhelmed, corneal decompensation and subsequent corneal oedema develop. IDENTIFYING THE INCTING CAUSE- A METHODICAL WORKUP When an ulcer persists longer than 7 days or involves the stroma it should be assigned to one of the three categories: • The inciting cause persists To identify the cause, it is essential to pay special attention to eyelid 242 WSAVA GLOBAL COMMUNITY CONGRESS

● Additional topical treatment rate of superficial chronic corneal epithelial defects in dogs. J Am Vet Med Assoc. 2017;250(9):1014–22. Serum It is mainly used in patients with keratomalacia, where its antipro- teinase activity reduces the enzymatic digestions. It contains numerous 4. Gronkiewicz KM, Giuliano EA, Sharma A, Mohan RR. Effects of topical growth factors, immunoglobulins, fibronectin and vitamin A, which pro- hyaluronic acid on corneal wound healing in dogs: a pilot study. Vet Oph- mote cell proliferation and migration (2) and improves tear film breakup thalmol. 2017;20(2):123–30. times and pain scores in dry eye patients. However, more rigorous con- trolled studies on its clinical efficacy are required. Serum did not reduce 5. Gosling AA, Labelle AL, Breaux CB. Management of spontaneous time of reepitheliazation in SCCEDs (3). chronic corneal epithelial defects (SCCEDs) in dogs with diamond burr debridement and placement of a bandage contact lens. Vet Ophthalmol. Hyaluronic acid plays and important role in the corneal wound healing. In 2013;16(2):83–8. vitro and in vivo studies have confirmed its ability to promote healing, but topical administration in combination with standard medical treatment did 6. Wooff PJ, Norman JC. Effect of corneal contact lens wear on healing not accelerate healing (4). time and comfort post LGK for treatment of SCCEDs in boxers. Vet Oph- thalmol. 2015;18(5):364–70. ● Corneal bandage lens (CBL) 7. Dees DD, Fritz KJ, Wagner L, Paglia D, Knollinger AM, Madsen R. Effect Placement of a CBL in addition to standard treatment has been intensely of bandage contact lens wear and postoperative medical therapies on cor- studied in SCCED patients. CBLs are safe to use in this setting, signifi- neal healing rate after diamond burr debridement in dogs. Vet Ophthalmol. cantly decreased median healing time when retained, but might not affect 2017;20(5):382–9. subjective comfort scores (5–7). 8. Jirsova K, Jones GLA. Amniotic membrane in ophthalmology: prop- Most recently corneal bandage lenses were used to secure amniotic mem- erties, preparation, storage and indications for grafting—a review. Cell brane (AM) in place. AM supports epithelialization and exhibits anti-fi- Tissue Bank. 2017;18(2):193–204. brotic, anti-inflammatory, anti-angiogenic and anti-microbial features (8). The combined use with a CBL has been efficient in treating persistent or 9. Maqsood S, Elsawah K, Dhillon N, Soliman S, Laginaf M, Lodhia V, et al. non-healing ulcers of various etiologies in humans (9). Further AM extract Management of persistent corneal epithelial defects with human amniotic is available as a drop, but did not show a significant benefit in the healing membrane-derived dry matrix. Clin Ophthalmol. 2021;15:2231–8. rate for equine superficial corneal ulcers (10). 10. Lyons VN, Townsend WM, Moore GE, Liang S. Commercial amniotic ● Surgical treatment/ interventions membrane extract for treatment of corneal ulcers in adult horses. Equine Vet J. 2020;1–9. Corneal burring or debridement under topical anaesthesia is a potent treatment for SCCEDs in dogs, but contraindicated in all other types of 11. Michau TM, Gilger BC, Maggio F, Davidson MG. Use of thermoker- ulcers and erosions and should not be performed in cats. Some SCCEDs atoplasty for treatment of ulcerative keratitis and bullous keratopathy require superficial keratectomy in general anaesthesia for remove of the secondary to corneal endothelial disease in dogs: 13 Cases (1994-2001). abnormal corneal tissue and achieve healing. J Am Vet Med Assoc. 2003;222(5):607–12. Corneal collagen crosslinking should be considered for cases with 12. Horikawa T, Thomasy SM, Stanley AA, Calderon AS, Li J, Linton LL, infectious and sterile keratomalacia with a remaining stromal thickness et al. Superficial keratectomy and conjunctival advancement hood flap of more than 50%. It increases the cornea’s resistance to digestion and (SKCAHF) for the management of bullous keratopathy: Validation in dogs reduces the microbial load killing bacteria, viruses and fungi. with spontaneous disease. Cornea. 2016;35(10):1295–304. Corneal grafting procedures are generally recommended for ulcers with a stromal loss of more than 50%. Corneal endothelial dysfunction with sec- ondary bullous keratopathy and corneal ulceration also requires surgical management (11,12). In the past, third eyelid flaps have been widely used, but should be avoided as they are associated with two unwanted effects- they prevent topical medication to reach the ocular surface and don’t allow monitoring of the healing process. Their only indication remains feline acute corneal hydrops. CONCLUSION Key to successful treatment of complicated corneal ulcers is performing a methodical work up, removing/ treating of the inciting cause and manag- ing client’s expectations with the knowledge on corneal wound healing. References 1. Whitley RD, Hamor RE. Diseases and Surgery of the Canine Cornea and Sclera. In: Gelatt KN, editor. Veterinary Ophthalmology. 6th ed. Hoboken: Wiley Blackwell; 2021. p. 1082–172. 2. Geerling G, MacLennan S, Hartwig D. Autologous serum eye drops for ocular surface disorders. Br J Ophthalmol. 2004;88(11):1467–74. 3. Eaton JS, Hollingsworth SR, Holmberg BJ, Brown MH, Smith PJ, Maggs DJ. Effects of topically applied heterologous serum on reepithelialization 243

13–15 NOVEMBER, 2021 0165 ables can now be monitored non-invasively. Although their reliability and accuracy may not still match 100% the actual cardiovascular status of the WHAT IS NEW IN VETERINARY ANESTHESIA? patient, they may allow for the evaluation of some trends (i.e. non-invasive REVIEW OF NEW ANESTHETIC AGENTS AND cardiac output, oxygen consumption, peripheral perfusion, etc). Similarly, TECHNIQUES neurophysiological monitoring is now more accessible to the veterinary practitioner, although not many monitors have been adapted, let alone vali- P. Larenza dated, for use in the anesthetized animal. Camperdown/Australia RESEARCH ON ANESTHESIA-RELATED MORBIDITY AND MORTALITY - One of the most important advancements in veterinary anesthesia regards Qualifications: the research on anesthetic techniques and/or drugs and their influence on short and long term survival and the incidence of determined disease M. Paula Larenza Menzies processes. World-wide multi center studies have been conducted in order to identify risks factors associated with short-term survival in almost all DVM, Dr.Med.Vet., PhD, EBVS® European Specialist in Veterinary Anaes- domestic species. At a lesser extent, risk factors that may be associated thesia and Analgesia with incidence of regurgitation, cancer recurrence and perianesthetic infections have also been evaluated in clinical and in-vitro studies. paula_larenza@hotmail.com NEW DRUGS USED IN VETERINARY ANESTHESIA - Recent advances in RENAISSANCE OF LOCOREGIONAL TECHNIQUES - With the development veterinary anesthetic drug development have been primarily focused on of neurostimulators, more access to ultrasonography and following the modifying the chemical structures of existing drugs in order to improve steps of human anesthesia trends, there has been an explosion of local their pharmacodynamic and pharmacokinetic effects. In the past 10—15 anesthetic techniques developed for small animals. These technologies years, active enantiomers of well established racemic agents have been make the administration of local anesthetics at the target site much more developed and marketed for animal use (e.g. S-ketamine, dexmedetomi- reliable, allowing for a more efficacious management of the intraoperative dine). These agents have the ability to provide similar properties as the and postoperative. These techniques have also helped the veterinarians parent compounds with the advantage of using half of the dose and often to work with opioid-free techniques, specially in the presence of a global showing faster elimination profiles, thus providing faster recoveries from opioid crisis which not only affected the human medicine industry but also anesthesia/sedation. In the case of the local anesthetics, efforts have several veterinary practices. been made to extend the duration of action of commonly used drugs. This is the case of bupivacaine liposome injectable suspension, a local EDUCATION AND CHECKLISTS - Today’s veterinary students have more anesthetic formulation that contains multivesicular liposomes that en- consistent and reliable education in the field of veterinary anesthesia capsulate aqueous bupivacaine, therefore reducing the elimination of this compared with 10 or 20 years ago. This is probably the consequence of local anesthetic and prolonging its duration of action for up to 72 hours. the development and institution of the veterinary anesthesia specialty by Recently, the rediscovery of an old molecule, vatinoxan (formerly known the Association of Veterinary Anaesthetists, and both the American and as MK-467 and L-659’066), that reverses the cardiovascular and gastroin- European Colleges of Veterinary Anesthesia and Analgesia, among other testinal side-effects, but not the sedative effects of alpha-2 adrenergic ag- relevant international institutions. The veterinary anesthesia community is onists has also been extensibly studied. On 7 October 2021, the European well represented worldwide in most countries and in veterinary colleges, Committee for Medicinal Products for Veterinary Use adopted a positive faculties and universities. In addition, the veterinary anesthesia education opinion, recommending the granting of a marketing authorization for a has been gaining many adepts in the veterinary technician and nursing solution containing containing medetomidine hydrochloride and vatinoxan groups around the world. Today, in order to obtain a specialty degree in hydrochloride to be used in dogs. the field, veterinarians, nurses and technicians should undergo intensive training and arduous examinations. All this has been translated in a better TARGET-CONTROLLED INFUSIONS - Innovations in computer technology, understanding of veterinary anesthesia as a whole and also in a better pharmacokinetic modeling, and IV infusion delivery devices have fostered dissemination of the knowledge. As a consequence, numerous working the development intravenous agents. When using pharmacokinetic-de- groups have developed an array of safety check lists, anesthetic proto- rived models specific to a particular drug, a computerized pump system cols, scales and algorithms aiming to facilitate the delivery of anesthesia incorporates patient characteristics (e.g. weight, age) to achieve a and analgesia and improve the safety and quality of such delivery. targeted serum-level concentration. This technology constantly estimates the concentration of a drug at the target and in the plasma, allowing the REFERENCES clinician to make changes based on clinical or physiological indicators. Argano M et al. Canine mammary tumour cells exposure to sevoflurane: AIRWAY MANAGEMENT AND VENTILATION - A variety of case specific effects on cell proliferation and neuroepithelial transforming gene 1 endotracheal tubes, supraglottic airway devices (e.g. laryngeal masks expression. VAA, 46:369-374; 2019. airway) and devices used to place these airway devices (fiber-optic bronchoscopes, video laryngoscopes) exist today. Some have been Barletta M & Reed R. Local Anesthetics: Pharmacology and Special Prepa- specifically developed for animal use and others have been adapted from rations.Vet Clin North Am Small Anim Pract. 49:1109-1125; 2019. human medicine. Modern ventilators reflect refinements in biomechanical engineering and allow for accurate lung ventilation and monitoring, even European Medicines Agency. Summary of positive opinion on Zenalpha. in small-sized animals. https://www.ema.europa.eu/en/medicines/veterinary/summaries-opinion/ zenalpha. Accessed October 18th, 2021. ANESTHESIA AND ANALGESIA MONITORING - Today’s anesthetic mon- itors are compact in size, affordable and can display a large amount of Larenza MP et al. Anaesthesia recovery quality after racemic ketamine variables in one screen. What seemed inaccessible in the past, has now or S-ketamine administration to male cats undergoing neutering surgery. been transformed in routine standard of care. With the advancement of Schweiz Arch Tierheilkd. 50:599-607; 2008. monitoring technologies and the use of internet, anesthetists and pain specialists can now provide assessment or advice on cases remotely - a Mahmoud M and Mason KP. Recent advances in intravenous anesthesia particularly good aid during COVID19. Many of the cardiovascular vari- and anesthetics. F1000Research:470; 2018. Obey DH et al. Prevalence and risk factors for canine post-anesthetic aspi- 244 WSAVA GLOBAL COMMUNITY CONGRESS

ration pneumonia (1999-2009): a multicenter study. VAA 41:127-36; 2014. 0166 Otero P. & Portela D. Manual of Small Animal Regional Anesthesia: Illus- ANESTHESIA FOR PATIENTS WITH CARDIAC trated Anatomy for Nerve Stimulation and Ultrasound-Guided Nerve Blocks DISEASE - Second edition. Buenos Aires, Argentina; Inter-Medica publisher; 2019. P. Larenza Camperdown/Australia Qualifications: M. Paula Larenza Menzies DVM, Dr.Med.Vet., PhD, EBVS® European Specialist in Veterinary Anaes- thesia and Analgesia paula_larenza@hotmail.com Patients with cardiac disease may present to anesthesia for reasons related to their cardiac abnormalities or they may need to be anesthetized for unrelated procedures. Maintaining acceptable levels of cardiac output and oxygen delivery throughout anesthesia is essential. Because stress activates the sympathetic nervous system and increases cardiac work, techniques should be employed to reduce/avoid stress in the cardiac compromised patient. The beneficial aspects of providing pre-operative tranquilizers and/or analgesics will potentially decrease the need of anesthetic agents. However, withholding sedation may be indicated in patients who cannot tolerate respiratory or cardiovascular depression. An- esthetic agents should be selected based on cardiac dysfunction to cause the least amount of disturbance to normal function. Usually, balanced anesthetic techniques are preferred in order to decrease doses of each agent thereby reducing detrimental side effects and also to provide multi- modal analgesia. Pre-oxygenation for about 5 minutes before anesthesia induction can enhance the alveolar oxygen concentration which in turn will provide enough oxygen to be transported by the hemoglobin for about 2 minutes after administration of induction agents. Fluids should be cal- culated to maintain normovolemia, hydration and blood pressure without overloading the ability of the myocardium to move blood forward. In addi- tion, intravenous fluids might be given to correct electrolytes imbalances, low colloid-osmotic pressure and anemia. However, as pulmonary edema due to fluid overload is of particular concern in patients with left-sided heart failure, in some patients intravenous fluids might be restricted. ANESTHETIC RISK ASSESSMENT Decisions about anesthetizing patient with heart disease should be based on degree of disease as well as the type of disease. The American Society of Anesthesiologists (ASA) classification for patients with regard to anes- thetic risk is described in the table below. A classification of patients with heart disease has been developed by the International Small Animal Car- diac Health Council (ISACHC) in 1994 and can be compared with the ASA anesthetic risk classification. Patients with mild cardiovascular changes may be considered as low anesthetic risk (ASA II). On the other hand, patients with exercise intolerance and mild respiratory complications may be considered of a moderate risk (ASA III) and patients with evident signs of congestive heart failure may be classified as high anesthetic risk (ASSA IV & V) and may need additional supportive therapies during anesthesia. Table 1.- Comparison between the anesthetic risk classification as per the American Society of Anesthesiologists (ASA) and a classification of patients with heart disease developed by the International Small Animal Cardiac Health Council (ISACHC). ASA ISACHC I A normal healthy patient 245

13–15 NOVEMBER, 2021 II Patient with mild systemic I a Asymptomatic; heart murmur they cause vasoconstriccion, bradycardia and reduce cardiac output. disease Ib Asymptomatic, cardiomegaly Hypertrophic cardiomyopathy (Rx, US) Hypertrophic cardiomyopathy (HCM) is the most commonly seen heart Patient with severe systemic Exercise intolerance, cough, disease in cats, and is usually associated with hyperthyroidism. HCM disease is characterized by thickening of the left ventricular wall and decreased III II tachypnea, respiratory distress chamber size, all of which lead to a poor relaxation of the ventricle, par- ticularly during diastole. As a result, the ventricular filling time is reduced (mild), ascites. with an inadequate stroke volume. This makes cardiac output particularly rate dependent, thus tachycardia must be avoided. Tachycardia may IV Patient with severe systemic III Clinical signs of heart failure at impede relaxation and perfusion of the myocardium and may increase disease that is a constant threat a rest myocardial oxygen consumption. Therefore, when handling patients with to life HCM, particularly in cats with hyperthyroidism, avoidance of stress is vital since they are prone to tachyarrythmias. V Moribund patient III Cardiogenic shock, requires b hospitalization Anesthesia premedication regimes in these cases are somewhat challeng- ing as most cardiovascularly sparing agents like opioids and benzodiaze- ANESTHETIC CONSIDERATIONS FOR PARTICULAR CARDIAC pines do not always provide reliable sedation in cats. However, sedation DISEASES may be endeavored by combining an opioid (0.2-0.4 mg/kg of butorphanol or 0.2 mg/kg methadone) with a benzodiazepine (0.2 mg/kg of midazol- Dilated Cardiomyopathy and Mitral Valve Insufficiency am) and a low dose of an alpha-2 agonist such as dexmedetomidine (0.5- 3 mcg/kg), all intramuscularly. This drug combination usually provides Mitral valve insufficiency is a common cardiac disorders in dogs. A reliable sedation in most cats while bradycardia and hypertension may be defective mitral valve allows some blood to be pumped back into the left seen. Alternatively, instead of an alpha-2 agonist, alfaxalone may be given atrium therefore reducing cardiac output and systemic blood pressure. intramuscularly together with a benzodiazepine and an opioid. Controver- Dilated cardiomyopathy is a condition seen in medium to larger breed sies exist in regards to the use of ketamine in these cases, as it usually dogs. It is characterized by the stretching and weakening of the heart increases heart rate. Nevertheless, the benefits of intramuscular ketamine muscle, with increases in that chamber size and reduced myocardial con- administered at low doses (2-4 mg/kg) with an opioid and a benzodiaz- tractility. Chamber enlargement may alter the shape and function of the epine may outweigh the risk of tachycardia, especially in fractious cats. mitral valve, leading to valvular insufficiency. In both conditions, changes Anticholinergics are usually not administered as part of the premedication in myocardial architecture disrupt cell communication and leading to as they may induce tachycardia. arrhythmias (i.e.: atrial fibrillation, premature ventricular contractions and ventricular tachycardia). Stroke volume is reduced resulting in decreased Induction of anesthesia is usually achieved with propofol at 1-4 mg/kg IV blood pressure. Compensatory mechanisms for hypotension happen (i.e. or with midazolam at 0.2 mg/kg IV and alfaxalone 1-2 mg/kg IV. Fentanyl increases in systemic vascular resistance as a result of vasoconstriction). (1-2 mcg/kg) may also be included. Maintenance of general anesthesia These patients are at grave risk of developing pulmonary edema/conges- may include isoflurane or sevoflurane in oxygen, at 1 MAC. Opioids and tive heart failure. locoregional techniques may be used pre/intra-operatively to decrease the requirements of inhalant anesthetics. Although bradycardia is better When anesthetizing a patient with dilated cardiomyopathy or mitral valve tolerated than tachycardia in these cases, excessive bradycardia (i.e. HR insufficiency, the goal is to maintain contractility and a normal heart below 80) may necessitate treatment with low doses of anticholinergics rate. Bradycardia, tachycardia and vasoconstriction should be avoided. (atropine or glycopyrrolate 5-10 mcg/kg IV). Adequate IV cryatalloid thera- Premedication may consist of an intramuscularly given opioid (0.2 – 0.5 py should be administered in order to prevent hypovolemia and decreased mg/kg of methadone or 0.2 mg/kg of butorphanol). An anticholiner- filling volumes. An IV fluid rate of a balanced electrolyte solution may gic (0.01mg/kg glycopyrrolate or atropine) may be also administered be administered at a rate of 2-5 ml/kg/hour. Alpha-adrenergic agonists depending on patient’s heart rate. Low doses of acepromacine (0.005- such as phenylephrine may be required to treat hypotension. An increase 0.02 mg/kg) might be considered in case of excessive vasoconstriction in contractility or heart rate is undesirable, therefore beta-adrenergic or to enhance the sedative effects of opioids. Following pre-oxygenation agonists such as dobutamine are not recommended. (2–5 minutes), induction may be achieved with midazolam at 0.2 mg/kg given IV associated with etomidate (1–2 mg/kg) or alfaxalone (1–2 mg/ REFERENCES kg) given IV to effect. Ketamine is not recommended in patients that are tachycardic or have had tachyarrhythmias. High doses of propofol may Pascoe, P. Anesthesia for Patients with Cardiovascular Disease. Proceed- cause significant decreases in contractility and vasodilation causing ings of the Spring Meeting of the Association of Veterinary Anaesthetists. hypotension. However, propofol (1–2 mg/kg) and ketamine (1–2 mg/kg) Rimini, Italy; 2005. may be used in association as induction agents aiming to minimize their individual side effects. Anesthetic maintenance may include isoflurane or sevoflurane in oxygen, at 1 minimum alveolar concentration (MAC). Constant rate infusions of fentanyl may be used at 2–10 mcg/kg/h to de- crease the delivered concentrations of the inhalants. Hypotension may be corrected with the use of beta-adrenergic agonists such as dobutamine. These drugs focus on improving contractility without increasing afterload. Dobutamine should be diluted and administered as a constant rate infu- sion, beginning at 2 mcg/kg/min, and increased as needed (up to 10 mcg/ kg/min). Dopamine as a CRI may also be used to support blood pressure and is calculated to be delivered at a starting rate of 2–10 mcg/kg/min. High doses of dopamine (i.e. 15-20 mcg/kg/min) may cause vasoconstric- tion and should be avoided. Ventricular arrhythmias may be exacerbated with the use of these vasoactive agents, therefore close monitoring of the electrocardiogram is necessary. Fluids must be administered conserva- tively, to avoid overload and pulmonary edema. Alpha-2 adrenergic agonist (i.e. xylazine, medetomidine) are not recommended for these patients as 246 WSAVA GLOBAL COMMUNITY CONGRESS

0167 builds on the work of all preceding researchers. USING ANONYMIZED CLINICAL RECORDS AS Data Sharing BIG DATA TO GENERATE COMPANION ANIMAL EVIDENCE: THE VETCOMPASS UK EXPERIENCE VetCompass shares deidentified data on all animals under veterinary care at a wide range of partner practices and practice groups (4). The D. O’Neill VetCompass concept is that veterinary practices already record large and sufficient volumes of electronic information on their practice management Hatfield/United Kingdom systems (PMS) and that it is unnecessary to ask practices to record any additional data. Consequently, participation in VetCompass requires no Qualifications: updates to current data entry processes at the point of clinical care. This lowers the barriers for participation from the clinical perspective and has Dan O’Neill promoted widespread interest in the VetCompass approach from veteri- MVB BSc(hons) GPCert(SAP) GPCert(FelP) GPCert(Derm) GPCert(B&PS) nary professionals and organisations in the UK. PGCertVetEd FHEA MSc(VetEpi) PhDFRCVS doneill@rvc.ac.uk VetCompass is compliant with general data protection regulations (UK GDPR). The PMS data fields that are shared with VetCompass exclude Background fields deigned to hold information on humans or that may be otherwise sensitive. Client data fields covering names, addresses and contact Until recently, veterinary beliefs about important health issues affecting information are not shared, nor are fields covering financials. A par- the wider general population of companion animals were largely shaped tial postcode is shared to facilitate geographic analyses but without by expert opinion (‘eminence-based veterinary medicine’) or based on breaching personal de-identification. The fields that are shared include information derived from referral-based studies. Although often highly species, breed, sex, neuter, date of birth, colour, insurance, microchip persuasive, expert opinion is now regarded as a weak source of evidence and bodyweight. All clinical notes and items sold are also shared, along because the belief systems of any individual expert are inevitably framed with relevant dates. Deidentified ID codes are shared that allow individual by many cognitive biases. Likewise, referral studies may offer useful infor- animals to be followed over time within veterinary groups. These data mation for referral specialists but are now accepted as often being poorly enable a broad picture of the animal and its clinical care to be generated generalisable to the wider companion animal population. There is now and explored during analyses. Clients are informed about the practice’s increasing recognition of the valuable contribution to knowledge creation participation via posters and leaflets within the practice as well as on from analyses of first opinion veterinary clinical records. This presentation practice websites, social media and registration forms. Clients are offered will bring you on the journey that the Royal Veterinary College has taken opt-out consent for sharing data relating to their own animals. in the UK over the past 10 years to build the VetCompass concept of primary-care companion animal veterinary research. And we will explore Data sharing occurs in the back end of the PMS and requires no manual how the VetCompass concept is now expanding to embrace broader par- input or effort from the practices. Data sharing covers a standard list of adigms including other species, geographies and data sources. With this fields defined by VetCompass. Automated data queries are defined for background, I welcome you into my exciting and entrancing world of Vet- each PMS and/or practice group and these queries run nightly such that Compass Big Data epidemiology based on primary-care clinical records. VetCompass data are quasi-realtime. Data are shared in encrypted for- mats and via secure pathways. Each of the many incoming data sources Ethos to VetCompass are reformatted to a standard format before their upload to the VetCompass research database. Building on several years of previous Royal Veterinary College work, the ‘VetCompass Programme’ formally came into being from 2010 during my Researcher data access PhD that aimed to report on the comparative health of purebred versus crossbred dogs and cats in the UK (1, 2). The VetCompass concept is The VetCompass concept embraces the rich complexity of the prima- predicated on a series of key maxims: ry-care veterinary world. Sophisticated methods to collate, clean, structure and interrogate data have been developed to capture the full complexity Epidemiology is one of man’s most powerful tool to understand the of the rich clinical data recorded by the thousands of veterinary pro- real-world of veterinary care and animal welfare. fessionals sharing data with VetCompass. To this end, all VetCompass researchers work in a single virtual research space and build on the same Health issues of companion animals generally have complex ‘webs of underlying dataset. New researchers gain hugely from the prior cleaning causation’ and require collection of information on many factors to enable and coding done by hundreds of previous researchers, and in turn are multivariable analytic methods that account for confounding (3). benefitting the work of researchers yet to come. Primary-care veterinary teams work in highly complex and busy environ- VetCompass operates to high levels of data security. Incoming raw data ments and should not be asked to do anything extra AT ALL at the point of shared by veterinary practices never leave the VetCompass environment. clinical care. Instead, researchers access and work on the data by accessing the VetCompass research database online at vetcompass.org. Each research- All proposed VetCompass studies must have a strong a priori welfare er signs a stringent agreement specifying their data security and usage statement before study authorization. responsibilities before being given access to the required study denomina- tor of animals for their work. Every study requires formal ethics approval VetCompass operates on a not-for-profit basis. before commencement. VetCompass embraces, and is nourished by, wide collaboration. Current UK status Wide dissemination of VetCompass results to all relevant stakeholders, Currently, 1803 (>30% of all) UK veterinary clinics have shared data on >20 including owners, is a key step towards maximising real-world animal million companion animals. VetCompass now holds >60 million measure- welfare impact. ments, >200 million clinical notes and >500 million treatments. VetCompass operates in a cumulative learning environment. Each study 247

13–15 NOVEMBER, 2021 Publications to date 0168 Up to Sept 2021, there have been 91 VetCompass peer-reviewed publica- USING ANONYMIZED CLINICAL RECORDS AS tions that are available on the VetCompass website (4). These papers are BIG DATA TO GENERATE COMPANION ANIMAL almost all published under Gold or Green open access. Broad accessibility EVIDENCE: THE VETCOMPASS AUSTRALIA without paywalls is a key goal of VetCompass work. These papers cover a EXPERIENCE broad spectrum of topics areas, reflecting the complexity of the veterinary primary-care arena. These topic areas include species (dog, cat, rabbit) N. Dhand1, S. Masters1, C. Mansfield2, B. Hur2, J. Be- and breed (eg Pug, Chihuahua), single disorders (e.g. lipoma), infectious atty1, R. Squires3, M. Bruce4, M. Combs5, R. Soares disease (e.g. leptospirosis), pathophysiology (e.g. oncology), drug therapy Magalhaes6, J. Gilkerson2, A. Peaston7 (e.g. antimicrobials), pharmacovigilance (e.g. glucocorticoids), scientific methods (e.g. text-mining) as well as also crossing into human transla- 1Camden/Australia, 2Werribee/Australia, 3Townsville/Austra- tional work (e.g. aging). Authors and research teams for these studies lia, 4Murdoch/Australia, 5Wagga Wagga/Australia, 6Gatton/Austra- based on UK clinical data are spread worldwide, including Australia, US lia, 7Roseworthy/Australia and many countries in Europe. Qualifications: Wide dissemination of study findings is a key VetCompass goal. To this end, the publications of most VetCompass papers are now accompanied Navneet K Dhand with open access to some of the underlying data to assist students and other researchers, with a press release to share the core welfare messag- BVSc&AH, MVSc, MANZCVS (Epidemiology), PhD es with the wider public and also with a colorful infographic that summa- rized the key findings especially for a social media audience (4). navneet.dhand@sydney.edu.au VetCompass Australia is a nationwide companion animal surveillance Current and future directions system that collects data from >130 veterinary practices in Australia and provides collated data to researchers to analyse (1). Established in 2016 The VetCompass concept of primary-care research on companion animal with funding from the Australian Research Council, VetCompass Australia health using clinical records is now firmly embedded within veterinary involves representatives from all seven veterinary schools of Australia. research. To support this work, we continue to create robust methods for It uses a software program developed by the Royal Veterinary College, data collection, analysis, reporting and dissemination. Building on this University of London to import electronic patient records from veterinary novel and solid platform, the VetCompass concept has been extended practices into a centralised repository. These data are then transformed over recent years to cover new paradigms including: using relational database queries and made available to researchers and students to analyse for answering research questions about the frequency International: VetCompass Australia is now firmly established as con- and distribution of health problems in companion animals. VetCompass sortium of Australia’s seven veterinary schools (5) with several papers Australia is managed by an Executive Board comprising of representatives already published. There are also plans for VetCompass projects in coun- from six veterinary schools. Supported by a Project Manager, the Board tries including Singapore, Ireland, Germany, Spain and the US. meets monthly to make strategic and policy decisions. Species: In addition to small companion animals, VetCompass in the UK VetCompass projects also has projects working on equine and cattle species (4) VetCompass Australia offers four types of projects: Student, Strategic, Referral practices: Data sharing in the UK now also extends to several Major and Operational. referral hospitals and there are already many projects underway exploring these referral data. Student projects are open to students enrolled in a veterinary programme in Australia and focus on determining longevity, bodyweight curve, Artificial Intelligence (AI): With access to such a vast veterinary dataset, disease frequency or certain pharmacotherapy issues for a specific breed. VetCompass continues to expand its development of AI methods includ- Working under the supervision of a supervisor or advisory team, students ing machine learning and natural language processing to continuously manage and analyse data and prepare reports or dissertations. Currently, improve our information extraction over time. 71 breeds have been selected for student projects. Protocols for data management and analyses developed by a team of epidemiologists are References provided to students to support them in conducting their projects. 1. O’Neill DG, Church DB, McGreevy PD, Thomson PC, Brodbelt DC. Strategic projects are offered to early- to mid-career researchers or clini- Prevalence of disorders recorded in cats attending primary-care veterinary cal investigators. The number of strategic projects offered to a university practices in England. The Veterinary Journal. 2014;202(2):286-91. depends on their relative financial contribution to the project. The project proposals are only considered if they do not duplicate a current strate- 2. O’Neill DG, Church DB, McGreevy PD, Thomson PC, Brodbelt DC. Prev- gic or major project and have realistic goals and scope. Currently, 56 alence of disorders recorded in dogs attending primary-care veterinary approved strategic projects are being carried out. practices in England. PLoS ONE. 2014;9(3):1-16. Major projects are large externally funded projects. Currently, VetCom- 3. O’Neill DG, Pegram C, Crocker P, Brodbelt DC, Church DB, Packer RMA. pass Australia is supporting four major projects investigating the burden Unravelling the health status of brachycephalic dogs in the UK using multi- of infectious diseases, the effectiveness of antimicrobial stewardship, the variable analysis. Scientific Reports. 2020;10(1):17251. impact of canine obesity and snake envenomation. VetCompass Australia also supports four operational projects, primarily aimed at improving the 4. VetCompass. VetCompass Programme London: RVC Electronic Media VetCompass Australia database, systems, or stakeholder engagement. Unit; 2021 [Available from: http://www.rvc.ac.uk/VetCOMPASS/. 5. VetCompass Australia. VetCompass Australia Sydney: The University of Sydney; 2021 [Available from: http://www.vetcompass.com.au/. 248 WSAVA GLOBAL COMMUNITY CONGRESS

Case studies the results which can be very time consuming and error prone. To solve this problem, we will pre-process the text with natural language process- VetCompass Australia currently holds > 30 million consultation records, ing to assign Veterinary Nomenclatures diagnostic codes which will vastly which have been used by researchers and students to investigate a wide improve the search facility. Secondly, VetCompass Australia currently range of diseases, conditions, and risk factors (2-5). Three case studies only provides data to researchers, who conduct analyses using varied ap- from the research conducted based on VetCompass Australia data are proaches, which reduces the comparability of results. To solve this prob- presented below and will be discussed further at the conference. lem, we will develop pipelines of analyses for some specific policy/clini- cally relevant research questions and provide access to researchers to a Case study 1: Early age desexing of cats single unified data analysis portal which will improve comparability and reproducibility of findings. Similarly, veterinary clinics currently capture Desexing cats before puberty is a safe and recommended practice, but pathological data inconsistently with most clinics adding only summary objective information about the uptake of this practice in Australia was data leaving detailed reports in separate files that cannot currently be not available. Cats born between 1 January 2010 and 31 December 2017 accessed by VetCompass Australia. We are developing a system to ingest were identified from VetCompass data. Desexing status was recorded data from pathology PDFs and then link them to the animal’s VetCompass for 52,941 cats, of which 83.6% were desexed. The median age at which Australia record. This will enable us to better understand pathological cats were desexed was 6 months. Of the desexed cat population, 23.2% processes across a highly representative animal population. had been desexed by 4 months of age and 62.6% by 6 months of age. The odds of being desexed were significantly higher in males than females VetCompass Australia has developed four categories of research projects and of mixed breed cats than purebred cats. Being desexed was less likely as described above, but so far most of these projects have been initi- in areas with less access to resources, more low-income households, and ated by the Executive Board or academics/students at the associated greater relative socioeconomic disadvantage. Early age desexing was veterinary schools with limited involvement of veterinary practitioners who more likely to have been carried out among desexed cats born between provide the data. The problems faced by private practice veterinarians, 2010 to 2017, than in those born previously indicating a clear shift over and hence their priority research questions, could be different than veter- time towards desexing cats at a younger age. However, only 21.5% of inary academics or clinicians working at university clinics. Therefore, we desexed females were desexed before 4 months of age. Thus, valuable in- are planning to conduct a stakeholder consultation to reach out to small formation was gained about the age of desexing in cats in Australia using animal veterinary practitioners, particularly those who are providing data VetCompass Australia data. A paper based on this study is published (6). to VetCompass Australia, to identify their problems and prioritise ques- tions. This will enable us to create a pool of questions that are important Case study 2: Megaoesophagus in dogs for general veterinary practitioners in Australia and will also improve our engagement with our stakeholders. The second case study investigated megaoesophagus in dogs, conduct- ed following the detection of an outbreak of megaoesophagus in police VetCompass Australia has made substantial achievements within the first working dogs in early 2018. Clinical records were retrieved from the five years of being established. We are now extending and refining the VetCompass Australia database using keywords ‘vomiting’, ‘regurgitation’, system to improve our processes and the quality of data. VetCompass and ‘megaoesophagus’ (or their variants). The age of the animal was Australia is expected to continue to provide data to students, researchers, calculated from the animal’s date of birth. The incidence of megaoesoph- and clinicians to generate evidence for making evidence-based policy and agus was calculated using survival analysis. Consultations for 1,160,940 practice decisions. dogs meeting the selection criteria were available, of which 1312 dogs were over 6 months of age and had the term ‘megaoesophagus’ (or one of its variants) recorded on at least one occasion in the consultation record. There was a 7-fold increase in the incidence rate of canine megaoesopha- gus from 2014 to 2018 with the incidence increasing from 0.11 cases per 100,000 dogs per day in 2014 to 0.82 cases per 100,000 dogs per day in 2018. In a follow-up case-control study, the feeding of a particular thera- peutic diet was found to be associated with the outbreak (7). Case study 3: Antimicrobial prescribing patterns The third case study showcases the use of natural language processing to analyse text data. Although the VetCompass Australia database contains several fields containing numerical or categorical data, a lot of informa- tion in the patient consultation record is contained in a free text format, which is quite challenging to analyse. This study was conducted using cutting edge machine learning approaches to describe the antimicrobial usage patterns of companion animal veterinary practices by free-text anal- ysis of more than 4.4 million consultation records. The results indicated that critically important antimicrobials including cefovecin, polymyxin, enrofloxacin and other fluoroquinolones are being prescribed. However, they were used very sparingly, and most antimicrobials used in companion animal practice are of medium or low risk. Please refer to the published articles (8-10) for further information. Future directions VetCompass Australia has recently obtained additional funding from Australian Research Data Commons(ARDC) to strengthen its data asset, expand its capabilities and to solve some of the technical issues. As dis- cussed above, a lot of VetCompass Australia data is in the form of a free text. Currently, researchers manually query it using search terms and read 249

13–15 NOVEMBER, 2021 0169 tion of low volumes of low concentrated antigens, followed by less fre- quent injections of higher volumes and concentrations. The maintenance ALLERGEN SPECIFIC IMMUNOTHERAPY injection scheme is usually one ml of the full concentration once a month. C. Noli Oral immunotherapy is glycerol-based and has higher stability and better tolerability, although it should be administered once or twice daily. CN/Italy Intranodal ultrasound guided allergen injection has been recently Qualifications: described and is a promising alternative to SC or SL therapy: doses and concentration of allergens are much smaller and side effects are reduced. Chiaa Noli Rush immunotherapy has been described to be safe and effective in both DVM, Dip ECVD cats and dogs. With this protocolk the entire induction phase is conducted in one day (instead of several weeks) in the clinic, under strict monitoring. info@dermatologiaveterinaria.it The animal is then sent home with just the maintenance dose and concen- tration to be injected once a month. This protocol has the advantage of Introduction making the administration easier for the owner, who will not undergo the whole induction scheme, for a better treatment compliance. Atopic dermatitis is defined as the allergi reaction towards environmental allergens, these include mites, epithelia, pollen, moulds and yeasts. In Efficacy order to decrease pruritus and clinical lesions a symptomatic therapy is initiated. However, there is also the possibility to administer an etiologic Good to very good responses are achieved in 50-80% of dogs and cats therapy, able to normalize the pathological immune response to harmless treated. Usually one third of the animals experience no improvement, one aìenvironmental allergens. The mechanism of action of allergen-specif- third a mild to good improvement and one third an excellent result, with no ic immunotherapy (ASIT) is the stimulation of T-regulatory tolerogenic need for further medications. Clinical results, as measured by a decrease lymphocytes, will induce immunitary tolerance towards the responsible in symptoms, are seen anywhere from one month to eight months after allergens. ASIT is thus an individualised therapy, customized on the starting treatment. If no improvement is seen by 12 months of therapy, allergic profile of every patient. Immunotherapy is indicated if the duration then mostr the patient should be regarded as a treatment failure. Efficacy of pruritus is more than four months of the year, if the duration is shorter, of subcutaneous and of sublingual therapy is similar in cats as in dogs. then maybe symptomatic therapy alone is more practical. Clinical results do not depend on the species, sex, reproductive state, Allergen identification breed, age of development of the first signs or of initiation of the therapy or type of allergens included in the vial (e.g. mites, pollens, etc). Some au- Allergen-specific immunotherapy is prepared after the identification of rel- thors are of the opinion that molds proteases can inactivate allergens and evant allergens through in vivo or in vitro allergy tests. These tests should advice to kepp them in a separate vial, while other authors did not observe be performed uniquely to identify the allergens responsible atopic derma- any difference in efficacy with molds being mixed with other allergens in titis, with the aim of producing an ASIT solution. Allergy tests should not the same vial. be used diagnose atopic dermatitis. Many non-atopic patients with pruritic skin disease due to other causes (such as dietary allergy or mange), and On factor that may influence efficacy id the number of allrgens included even clinically normal animals, may show positive reactions to one or both in the vial, as the higher the number, the smalle would be the amount of of these tests. False negatives results can occur in up to 10% of atopic the individual allegens in the therapy solution (which has a fixed volume). animals due to absence fo measurable allergen-specific IgEs. Another very important factor is the choice of the allergens (see below). Allergy testing can be in vitro (serum test) or in vivo (intradermal allergy Choice of the allergens for the composition of the therapy solution test). A meta-analysis of the two testing methods (in vitro versus in vivo) has failed to show the superiority of one or the other test when related to The choice of the relevant allergens is pivotal for the therapy success. the clinical outcome of immunotherapy. Serum in vitro test is the easiest Allergens should be chosen among those that resulted positive in in vitro option for the veterinary practitioner. Most of the more reliable vitro tests or in vivo test, but also present in the patients’s environment. Most dogs are based on the ELISA (enzyme linked immunosorbent assay) technique. and cats are allergic to house dust mites (Dermatophagoide farinae >> Both an indoor panel (mites, molds, flea, cat epithelium) as well as an Dermatophagoide pteronyssinus) and some also to storage mites (Acarus outdoor panel (trees, grasses, weeds) should be tested. Testing is usually siro, Tyrophagus putrescentiae, Lepidoglyphus destructor and Glycipha- carried out in specialized laboratories using monoclonal (more specific, gus mallei), even if the latter positivities may represent cross-reactions less sensitive) or polyclonal (less specific, more sensitive) antibodies to with storage mites. Depending on the geographical area dogs may also detect allergen-specific IgE in the patient’s serum. The test is easy to per- be allergic to trees (birch, olive, pine are aong the most frequent ones), form (just blood drawing) and is not influenced by concurrent corticoste- weeds (Cynodon, Lolium, Anthoxanthum), grasses (nettle, Parietaria, roid administration (except at higher depot immunosuppressive doses). Ambrosia, Artemisia, Tarassacum, Plantago etc) or moulds (Penicillum, A test with CCD-blocking technology should be chosen, in oder to avoid Aspergillus, Cladusporum). It is said that treesdo not cross react but false positive results related to clinically non-significant binding of IgE to having a short pollination season (a couple of weeks), it is not always CCD (cross-reactive carbohydrate determinants) bound on pollens. necessary to include them in the ASIT solution. With exception of Cynodon (Bermuda grass) all weeds are consider to cross react, as well as all Types of therapy solutions grasses among them, while molds probably do not cross react and need to be considered individually. Malassezia, flea and cat epithelium is also Different types of vaccine exist. Aqueous solutions in phenol based solu- often tested. Malassezia an flea can be treated, while cat allergens can be tions require more frequent injections, at least in the initial phase. Alum included in the vial. precipitated allergens or those in glycerin or glycol emulsions are released more slowly and require less frequent subcutaneous administration. Ad- Side effects ministration schemes in the induction phase vary among producers, and generally initially include the frequent (once or twice weekly) administra- On occasion side effects of SC immunotherapy such as increased pruri- tus, restlessness, anorexia, vomit or diareeha can be observed in the few 250 WSAVA GLOBAL COMMUNITY CONGRESS