Brigham and Women's Hospital Department of Surgery Harvard Medical School External Review 2017-2021

needs. In a long-running partnership with the Uniformed Services University of the Health Sciences, CSPH has studied some of the most pressing health care challenges faced by military and civilian populations, demonstrating the absence of racially disparate outcomes in a universally insured population and providing evidence-based guidance for opioid prescribing practices. In recent years, CSPH has merged research with advocacy, serving as a leading voice in setting national research agendas and bringing needed focus and funding to critical areas. Joined by the National Institutes of Health and the American College of Surgeons, a 2015 symposium organized by CSPH resulted in the first national research agenda focused on surgical disparities. CSPH has since partnered with the ACS on several initiatives, including the Metrics for Equitable Access and care in Surgery (MEASUR) project, which developed hospital-level metrics sensitive to inequities in access, treatment and outcomes for surgical care. As part of this research agenda, CSPH is also leading a multisite trial at eight surgical residency programs across the country to develop, implement and evaluate a cultural dexterity curriculum aimed at improving a physician’s ability to deliver compassionate care to patients of all backgrounds. More recently, CSPH researchers have applied their expertise to the COVID-19 pandemic, establishing a surgical health services research agenda to assess the pandemic’s wide-ranging impacts on the United States surgical system, including changes to health care infrastructure, payment systems, safety standards, clinical training and population health. Subsequent studies have examined how to have shared decision-making conversations when caregivers and family cannot be present. Researchers have also examined the impact of cancer surgery and screening delays on clinical outcomes and patient experience. They have made the case for operationalizing equity in health system emergency response, using the experiences at the Brigham to build a case study on how to explicitly integrate equity into Hospital Incident Command Systems guidelines. Bringing together a diverse team of multidisciplinary experts at the intersection of surgery and public health, CSPH strives to make surgery safer, more patient-centered, and more accessible in the U.S. and around the world. Exemplary Publications Haider AH, Herrera-Escobar JP, Al Rafai SS, Harlow AF, Apoj M, Nehra D, Kasotakis G, Brasel K, Kaafarani HMA, Velmahos G, Salim A. Factors Associated with Long-Term Outcomes after Injury: Results of the Functional Outcomes and Recovery after Trauma Emergencies (FORTE) Multicenter Cohort Study. Ann Surg. 2020;271(6):1165-1173. PMID: 30550382. Lee KC, Sokas CM, Streid J, Senglaub SS, Coogan K, Walling AM, Cooper Z. Quality Indicators in Surgical Palliative Care: A Systematic Review. J Pain Symptom Manage. 2021 Jan 30: S0885-3924(21)00143-3. PMID: 33524478. Chaudhary MA, de Jager E, Bhulani N, Kwon NK, Haider AH, Goralnick E, Koehlmoos TP, Schoenfeld AJ. No Racial Disparities in Surgical Care Quality Observed after Coronary Artery Bypass Grafting in TRICARE Patients. Health Aff (Millwood). 2019;38(8):1307-1312. PMID: 31381404. 147

Scully RE, Schoenfeld AJ, Jiang W, Lipsitz S, Chaudhary MA, Learn PA, Koehlmoos T, Haider AH, Nguyen LL. Defining Optimal Length of Opioid Pain Medication Prescription after Common Surgical Procedures. JAMA Surg. 2018;153(1):37-43. PMID: 28973092. Jarman MP, Bergmark RW, Chhabra K, Scott JW, Shrime M, Cooper Z, Tsai T. The Surgical Health Services Research Agenda for the COVID-19 Pandemic. Ann Surg. 2020;272(3): e226-e229. PMID: 32541230. 148

The Gillian Reny Stepping Strong Center for Trauma Innovation Directors: Ali Salim, MD, and Julie Alperen, DrPH The Gillian Reny Stepping Strong Center for Trauma Innovation fosters multidisciplinary research and innovation, with the goal of preventing traumatic injuries before they occur and transforming the nature and delivery of trauma care. The center oversees the Innovator Award program, which provides $100,000 one-year grants to advance basic science research, clinical innovation and evidence-based interventions, with a focus on injury prevention, acute care, recovery and rehabilitation. The center also administers the Breakthrough Award that provides follow-up funding of up to $500,000 to previous Innovator Award recipients to accelerate the progress and scope of their research. The specific research areas of interest of the Stepping Strong Center align with the research priority topics outlined by the Centers for Disease Control for injury prevention and the National Trauma Research Action Plan for trauma research, as well as projects which translate military medical innovation to the civilian setting. The Stepping Strong Center has supported research teams at Mass General Brigham and beyond to advance a broad range of projects, which span this spectrum of trauma prevention and care, including: • Making the Invisible Visible: Bringing Intimate Partner Violence into Focus (PI: Bharti Khurana, MD) • Using Gene Therapy and Antibiotic Delivery to Treat Bone Infections (PI: Natalie Artzi, PhD) • Recovering Limb Function: A Surgical Approach for the 21st Century (PI: Matthew Carty, MD). This year, in a first for the center, the Breakthrough Award will support a multidisciplinary collaboration among three former Innovator Award recipients—Drs. Marc Wein, Ara Nazarian and Natalie Artzi—for their project, “Stimulating Fracture Healing by Blocking Salt Inducible Kinases.” Exemplary Publications Cites TR, Carty MJ, Ullauri JB, Carney ME, Mooney LM, Duval JF, Srinivasan SS, Herr HM. Proprioception from a Neurally Controlled Lower-Extremity Prosthesis. Sci Transl Med. 2018;10(443): eaap8373. doi: 10.1126/scitranslmed.aap8373.PMID: 29848665. 149

McCarty JC, Hashmi ZG, Herrera-Escobar JP, de Jager E, Chaudhary MA, Lipsitz SR, Jarman M, Caterson EJ, Goralnick E. Effectiveness of the American College of Surgeons Bleeding Control Basic Training Among Laypeople Applying Different Tourniquet Types: A Randomized Clinical Trial. JAMA Surg. 2019;154(10):923-929. PMID: 31339533. Tang CC, Castro Andrade CD, O’Meara MJ, Yoon SH, Sato T, Brooks DJ, Bouxsein ML, da Silva Martins J, Want J, Gray NS, Misof B, Roschger P, Blouin S, Klaushofer K. Velduis-Vlug A, Vegting Y, Rosen CJ, O’Connell D, Sundberg TB, Xavier RJ, Ung P, Schlessinger A, Kronenberg HM, Berdeaux R, Foretz M, Wein MN. Dual Targeting of Salt Inducible Kinases and CSF1R Uncouples Bone Formation and Bone Resorption. eLife. 2021;10e67772 doi: 10.7554/eLife.67772. PMID: 34160349. Khedigikar V, Charles JF, Lehoczky JA. Mouse LGR6 Regulates Osteogenesis In Vitro and In Vivo Through Differential Ligand Use. Bone. 2021 Nov 29; 155:116267. Online ahead of print. PMID: 34856421. Gosangi B, Park H, Thomas R, Gujrathi R, Bay CP, Raja AS, Seltzer SE, Balcom MC, McDonald ML, Orgill DP, Harris MB, Boland GW, Rexrode K, Khurana B. Exacerbation of Physical Intimate Partner Violence During COVID-19 Pandemic. Radiology. 2021;298(1): E38-E45. doi: 10.1148/radiol.2020202866. PMID:32787700. 150

Patient-Reported Outcomes, Value and Experience (PROVE) Center Directors: Andrea Pusic, MD, and Maria Edelen, PhD Founded in 2018 by Dr. Pusic, the mission of the PROVE Center is to expand the collection, analysis and use of patient-reported outcomes data in clinical care. The center focuses on using innovative techniques to study outcomes that matter most to patients and their caregivers. PROVE researchers specialize in qualitative and quantitative research methods, evidence synthesis, psychometrics (including computer adaptive testing) and health economic evaluations. With these skills, our multidisciplinary team aims to promote and operationalize high-value, patient-centered care at Mass General Brigham and around the world. In 2020, the PROVE Center welcomed associate director Dr. Edelen, a psychometrician and health policy researcher with a specific focus on patient-reported outcomes. The center has also expanded its support to include five Brigham surgery faculty members, one research faculty member, a postdoctoral research fellow, two research assistants, a program manager and an informatician. Furthermore, over the course of three years, the PROVE Center has supported 14 research fellows and residents, nine research trainees, as well as eight visiting scholars from the United Kingdom, Germany and the Netherlands. Since 2018, the PROVE team has published 70 papers in peer-reviewed journals that are related to patient-reported outcome measure (PROM) development and implementation, as well as comparative effectiveness studies that use PROMs to evaluate outcomes. They’ve also presented their work at 11 national and international conferences. An example of an important program initiated by the PROVE team is imPROVE Breast Cancer Care. imPROVE is an innovative electronic patient-reported data collection platform developed in collaboration with ADK Group, breast cancer care providers, patients at the Brigham and DFCI, and members of the Harvard Business School and the International Consortium of Outcomes Research (ICHOM). imPROVE consists of a patient-facing web application and clinician-facing portals developed through iterative cycles of feedback from patients and expert stakeholders. imPROVE has recently been implemented across the breast oncology and plastic surgery services at the Brigham and DFCI. 151

Exemplary Publications Klassen AF, Kaur MN, Tsangaris E, de Vries CEE, Bordeleau L, Zhong T, Cano SJ, Breitkopf T, Pusic AL. Development and Psychometric Validation of BREAST-Q Scales Measuring Cancer Worry, Fatigue, and Impact on Work. Ann Surg Oncol. 2021 May 24. doi: 10.1245/s10434-021-10090-2. Epub ahead of print. PMID: 34028633. Tsangaris E, Klassen AF, Kaur MN, Voineskos S, Bordeleau L, Zhong T, Broyles J, Pusic AL. Development and Psychometric Validation of the BREAST-Q Sensation Module for Women Undergoing Post- Mastectomy Breast Reconstruction. Ann Surg Oncol. 2021 May 14. doi: 10.1245/s10434-021-10094-y. Epub ahead of print. PMID: 33988795. Kaur MN, Klassen AF, Xie F, Bordeleau L, Zhong T, Cano SJ, Tsangaris E, Breitkopf T, Kuspinar A, Pusic AL. An International Mixed Methods Study to Develop a New Preference-Based Measure for Women with Breast Cancer: The BREAST-Q Utility Module. BMC Womens Health. 2021;21(1):8. doi: 10.1186/s12905- 020-01125-z. PMID: 33407389. Pusic AL, Temple LK, Carter J, Stabile CM, Assel MJ, Vickers AJ, Niehaus K, Ancker JS, McCready T, Stetson PD, Simon BA. A Randomized Controlled Trial Evaluating Electronic Outpatient Symptom Monitoring after Ambulatory Cancer Surgery. Ann Surg. 2021 Jun 16. doi: 10.1097/SLA.0000000000005005. Online ahead of print. PMID: 34132697. Pusic AL, Stetson P, Temple L. Remote Monitoring for Patients after Ambulatory Surgery – Is it Ready for Prime Time? JAMA Surg. 2021 Jun 2. doi: 10.1001/jamasurg.2021.1799. Online ahead of print. PMID: 34076693. 152

F. RESEARCH PROGRAMS In addition to the CSPH, the Stepping Strong Center and PROVE, the DOS has a number of dedicated research programs. Several of these are listed below. Laboratory for Surgical and Metabolic Research Bariatric surgery is the most effective therapy for obesity and associated metabolic disease, but the mechanism of action of these operations remains unclear. The Department of Surgery bariatric program is one of the largest clinical programs in the region and has created a comprehensive research program that covers basic science research (under the umbrella of the Laboratory for Surgical and Metabolic Research), clinical research, as well as health services and health policy research. Ali Tavakkoli, MD, and Eric Sheu, MD, have focused on studying mechanisms underlying anti-diabetic mechanisms of bariatric operations, with a focus on the molecular connections between the metabolic outcome of surgery and physiological changes in intestinal function, gut luminal factors (microbiota, bile acids, metabolites) and the immune system. The team has several animal models of surgery and translational studies of patients. Through their animal studies, Dr. Tavakkoli, in collaboration with Jeffrey Karp, PhD, from the Brigham, has developed a novel oral intestinal coating product that has shown promising anti-diabetic effects and has been licensed to a startup company. Dr. Sheu has recently discovered a novel gut-liver pathway activated by sleeve gastrectomy that leads to the production of an intestinal metabolite that improves glucose metabolism. The team is now working on manipulating this pathway as a new, non-invasive treatment for diabetes that mimics surgery. In collaboration with James Yoo, MD, another investigator within the Division of General and GI Surgery, the team is using models of bariatric surgery and colon cancer to understand the mechanisms by which bariatric surgery influences colon cancer pathogenesis. The lab is funded by the NIH, as well as nonprofit and society grants. We also have active collaborations with local investigators in microbiome, endocrinology and colon cancer. Past surgical residents in the lab have been highly productive, with high 153

impact publications and multiple national presentations, and have had success in obtaining extramural funding and research awards. Over the past five years, the group’s psychology team has started a collaboration with the Department of Psychiatry and the MGH Weight Center to study neurological changes after bariatric surgery. Functional MRIs were performed on sleeve gastrectomy patients prior to surgery, as well as six and 12 months after surgery. This important effort was one of the first in the world to demonstrate neural network changes that may help explain not only the power of the sleeve surgery but may be a key in explaining the variability in weight outcomes after surgery. The research was funded by the Harvard Nutrition Obesity Research Center, the Global Foundation for Eating Disorders and the Harvard Catalyst/The Harvard Clinical and Translational Science Center. A portion of the PIs’ time was provided by the National Institute of Mental Health and the Brigham BRI Fund for Research Excellence. Other research efforts – including multiple clinical studies and publications led by fellows and residents that have focused on a diverse list of topics related to bariatric surgery – include a collaboration with Dr. Pusic at the PROVE Center that has led to the generation of a novel PROM survey used to evaluate outcomes of bariatric operations. Dr. Tavakkoli has also been involved in several PCORI-funded projects focused on studying outcomes of bariatric operations at a national level. These studies have helped provide contemporary data on weight and metabolic outcomes of common bariatric operations and have been used by PCORI to generate several patient-focused educational materials. Exemplary Publications Chaudhari SN, Harris DA, Aliakbarian H, Luo JN, Henke MT, Subramaniam R, Vernon AH, Tavakkoli A, Sheu EG, Devlin AS. Bariatric Surgery Reveals a Gut-Restricted TGR5 Agonist with Anti-Diabetic Effects. Nat. Chem. Biol. 2021; 17(1): 20-29. PMID: 32747812. Harris DA, Mina A, Cabarkapa D, Heshmati K, Subramaniam R, Banks AS, Tavakkoli A, Sheu EG. Sleeve Gastrectomy Enhances Glucose Utilization and Remodels Adipose Tissue Independent of Weight Loss. Am J Physiol Endocrinol Metab. 2020; 318(5): E679-688. PMID: 32069072. Harris DA, Subramaniam R, Brenner T, Tavakkoli A, Sheu EG. Weight and Organ-Specific Immune Cell Profiling of Sleeve Gastrectomy in Mice. Metabolism. 2021 May; 118:154729. doi: 10.1016/j.metabol.2021.154729. Epub 2021 Feb 17. PMID: 33607195. Mou D, DeVries CEE, Pater N, Poulsen L, Makarawung DJS, Wiezer MJ, van Veen RN, Hoogbergen MM, Sorensen JA, Klassen AF, Pusic AL, Tavakkoli A. BODY-Q Patient-Reported Outcomes Measure (PROM) to Assess Sleeve Gastrectomy Vs. Roux-En-Y Gastric Bypass: Eating Behavior, Eating-Related Distress, and Eating-Related Symptoms. Surg Endosc. 2021 Aug;35(8):4609-4617. doi: 10.1007/s00464-020-07886-w. Epub 2020 Aug 19. PMID: 32815020. Courcoulas A, Coley RY, Clark JM, McBride CL, Cirelli E, McTigue K, Arterburn D, Coleman KJ, Wellman R, Anau J, Toh S, Janning CD, Cook AJ, Williams N, Sturtevant JL, Horgan C, Tavakkoli A; PCORnet Bariatric Study Collaborative. Interventions and Operations Five Years after Bariatric Surgery in a Cohort from the 154

U.S. National Patient-Centered Clinical Research Network Bariatric Study. JAMA Surg. 2020 Mar 1;155(3):194-204. doi: 10.1001/jamasurg.2019.5470. PMID: 31940024. Immunotherapy in Oncology Several DOS investigators who focus their clinical and research efforts in oncology have active programs investigating the role of immunotherapy in the treatment of cancer. We have highlighted two of them below. Dr. Ravindra Uppaluri Research Ravindra Uppaluri, MD, PhD, is a head and neck cancer surgeon/scientist with a longstanding interest in both basic and translational efforts in head and neck squamous cell carcinomas (HNSCC). His research program is focused on defining immunotherapeutic and signaling dependencies in HNSCC. These efforts include developing and interrogating robust pre-clinical models and extending these investigations to first-in-class clinical trials in surgically treated HNSCC patients. With respect to pre-clinical modeling, the Uppaluri Lab developed carcinogen-induced mouse oral carcinoma (MOC) models, which are transplantable cell lines that can be used in immunocompetent settings. The MOC models have significant parallels with the human disease, including carcinogen origin, conserved genomic alterations and biologic behavior, including regional and distant metastasis. These cell lines have become a platform for their work where they studied molecular signatures of metastasis, RAS/ERK/MAPK signaling pathways as HNSCC therapeutic targets, neoantigen targets of immunotherapy and anti-PD1 resistance. They have shared these MOC models with the entire head and neck research community; these models are now the most widely used mouse HNSCC model in the world. Using an immunogenomic approach, they identified a mutated ICAM-1 protein as a neoantigen target and have extended this work to both Class I and II targets. Dr. Uppaluri has been focused on extending findings from the lab to the translational, patient-centered setting. Given the ease of access to head and neck cancers, especially of the oral cavity subsite, his team has focused on the so-called “window of opportunity studies.” Dr. Uppaluri first led a window of opportunity clinical trial testing the impact of short course trametinib, an MEK inhibitor, in oral squamous cell cancer patients. This biomarker-based trial showed that these approaches can be safely completed in a multidisciplinary HNSCC setting. Extending this patient data, they have also focused on defining mechanisms of trametinib resistance. Their current work continues to examine response and resistance mechanisms to trametinib in HNSCC. To create a renewable resource of tumor tissue from patients pre- and post-treatment, they also developed a large bank of HNSCC patient-derived xenografts. Extending this clinical trial effort, Dr. Uppaluri also developed a neoadjuvant/adjuvant anti-PD1 clinical trial for surgically resectable HNSCC patients. This investigator-initiated clinical trial, funded by Merck, explored whether adding pembrolizumab pre- and postoperatively would impact clinical outcomes for the highest-risk HNSCC patients. An unexpected (for the time in 2016) finding from this work was that a 155

significant number of patients exhibited pathologic tumor responses (PTR) in the surgical specimens after a single preoperative dose of pembrolizumab. PTR thus represents an activated immune response and in several studies is correlated with clinical outcomes. To define response and resistance metrics, they completed detailed correlative work from these trial tumor specimens, including multiplex immunofluorescence and extended genomic analysis. Importantly, intriguing results from this Phase II clinical trial have led Merck to open an international Phase III trial, testing the exact concept described in our early work. They have also completed additional clinical trials testing other checkpoint inhibitors in oral cavity squamous cell carcinomas. Dr. Uppaluri’s immuno-oncology work has been funded by the NIH and V Foundation for Cancer Research, as well as industry. Exemplary Publications Uppaluri R, Winkler AE, Lin T, Law JH, Haughey BH, Nussenbaum B, Paniello RC, Rich JT, Diaz JA, Michel LP, Wildes T, Dunn GP, Zolkind P, Kallogjeri D, Piccirillo JF, Dehdashti F, Siegel BA, Chernock RD, Lewis JS Jr, Adkins DR. Biomarker and Tumor Responses of Oral Cavity Squamous Cell Carcinoma to Trametinib: A Phase II Neoadjuvant Window-of-Opportunity Clinical Trial. Clin Cancer Res. 2017 May 1;23(9):2186- 2194. doi: 10.1158/1078-0432.CCR-16-1469. Epub 2016 Nov 9. PMID: 28151720; PMCID: PMC5509449. Uppaluri R, Campbell KM, Egloff AE, Zolkind P, Skidmore ZL, Nussenbaum B, Paniello RC, Rich JT, Jackson R, Pipkorn P, Michel LP, Ley J, Oppelt P, Dunn GP, Barnell EK, Spies NC, Lin T, Li T, Mulder DT, Hanna Y, Cirlan I, Pugh TJ, Mudianto T, Riley R, Zhou L, Jo V, Stachler M, Hanna GJ, Kass J, Haddad R, Schoenfeld JD, Gjini E, Lako A, Thorstad W, Gay HA, Daly M, Rodig SJ, Hagemann IS, Kallogjeri D, Piccirillo JF, Chernock RD, Griffith M, Griffith OL, and Adkins DR. Neoadjuvant and Adjuvant Pembrolizumab in Resectable Locally Advanced, Human Papillomavirus-Unrelated Head and Neck Cancer: A Multicenter, Phase 2 Trial. Clin Cancer Res. 2020;26: 5140-5152. Note: Clinical Cancer Research featured article figure on the October 1 journal cover. Schoenfeld JD, Hanna GJ, Jo VY, Rawal B, Chen YH, Catalano PS, Lako A, Ciantra Z, Weirather JL, Criscitiello S, Luoma A, Chau N, Lorch J, Kass JI, Annino D, Goguen L, Desai A, Ross B, Shah HJ, Jacene HA, Margalit DN, Tishler RB, Wucherpfennig KW, Rodig SJ, Uppaluri R, Haddad RI. Neoadjuvant Nivolumab or Nivolumab Plus Ipilimumab in Untreated Oral Cavity Squamous Cell Carcinoma: A Phase 2 Open-Label Randomized Clinical Trial. JAMA Oncol. 2020 Oct 1;6(10):1563-1570. doi: 10.1001/jamaoncol.2020.2955. PMID: 32852531. R Uppaluri and RI Haddad, equal contribution. Shibata H, Xu N, Saito S, Zhou L, Ozgenc I, Webb J, Fu C, Zolkind P, Egloff AM, Uppaluri R. Integrating CD4+ T Cell Help for Therapeutic Cancer Vaccination in a Preclinical Head and Neck Cancer Model. Oncoimmunology. 2021 Aug 10;10(1):1958589. doi: 10.1080/2162402X.2021.1958589. PMID: 34408919. Mudianto T, Campbell KM, Webb J, Zolkind P, Skidmore ZL, Riley R, Barnell EK, Ozgenc I, Giri T, Dunn GP, Adkins DR, Griffith M, Egloff AM, Griffith OL, Uppaluri R. Yap1 Mediates Trametinib Resistance in Head and Neck Squamous Cell Carcinomas. Clin Cancer Res. 2021 Apr 15;27(8):2326-2339. doi: 10.1158/1078- 0432.CCR-19-4179. Epub 2021 Feb 5. PMID: 33547198. 156

Dr. Elizabeth Mittendorf Research A second DOS investigator focused on tumor immunology is Elizabeth Mittendorf, MD, PhD. Dr. Mittendorf is a fellowship-trained surgical oncologist who focuses her clinical and research efforts on the study of breast cancer. Dr. Mittendorf was one of the first breast cancer clinicians to consider a potential role for using therapy to enhance a patient’s immune response to help treat their malignancy. Her early efforts focused on the development of an HER2-targeted vaccine that was designed to elicit a CD8+ T cell response. Unlike previous investigators evaluating vaccines in patients with metastatic disease, Dr. Mittendorf and her colleagues administered their vaccine in the adjuvant setting to patients who were thought to be at high risk, with the intent to stimulate an immune response to prevent recurrence. Following a phase II study that demonstrated the vaccine to be safe and capable of decreasing the risk of recurrence from 20% to less than 10%, Dr. Mittendorf led an international phase III trial that enrolled more than 750 women and randomized them to vaccine versus placebo. Ultimately, the trial was stopped due to futility. Recognizing that the vaccine did not provide enough benefit as monotherapy, Dr. Mittendorf studied ways to enhance response to vaccination to include combining the vaccine with the HER2-targeted monoclonal antibody trastuzumab. Her preclinical studies showing synergism led to the design and conduct of two clinical trials looking at the combination; one in patients with HER2 1+/2+ breast cancer in whom trastuzumab would not routinely be administered as standard care. That trial demonstrated a significant benefit in women with hormone receptor negative HER2 1+/2+ breast cancer that had received preoperative systemic therapy and not experienced a pathologic complete response. The second study, funded by a prestigious grant from the Department of Defense, examined the combination therapy in women with HER2 3+ breast cancer. That trial has completed accrual and study intervention and is anticipated to report out in 2022. Dr. Mittendorf also studies immune aspects of the breast tumor microenvironment and the impact of standard therapy, as well as how immunologic aspects of the TME or a patient’s peripheral immune system impact therapeutic response. She was one of the first to show PD-L1 expression in triple- negative breast cancer. This led to her being the international PI on a phase III trial evaluating the anti- PD-L1 agent atezolizumab in combination with chemotherapy administered in the preoperative setting to patients with stage II or III triple-negative breast cancer. The trial enrolled more than 200 patients and importantly demonstrated an almost 20% increase in the rate of pathologic complete response. Dr. Mittendorf is currently investigating the use of atezolizumab combined with the antibody drug conjugate in an investigator-initiated trial supported by Stand Up To Cancer (SU2C), enrolling patients with triple-negative cancer who do not experience a pathologic complete response and are found to have circulating ctDNA as a marker of residual disease. Exemplary Publications Mittendorf EA, Lu B, Melisko M, Price Hiller J, Bondarenko I, Brunt AM, Sergii G, Petrakova K, Peoples GE. Efficacy and Safety Analysis of Nelipepimut-S Vaccine to Prevent Breast Cancer Recurrence: A Randomized, Multicenter, Phase III Clinical Trial. Clin Cancer Res. 2019 Jul 15;25(14):4248-4254. doi: 10.1158/1078-0432.CCR-18-2867.PMID: 31036542 157

Waks AG, Stover DG, Guerriero JL, Dillon D, Barry WT, Gjini E, Hartl C, Lo W, Savoie J, Brock J, Wesolowski R, Li Z, Damicis A, Philips AV, Wu Y, Yang F, Sullivan A, Danaher P, Brauer HA, Osmani W, Lipschitz M, Hoadley KA, Goldberg M, Perou CM, Rodig S, Winer EP, Krop IE, Mittendorf EA*, Tolaney SM*. The Immune Microenvironment in Hormone Receptor-Positive Breast Cancer Before and After Preoperative Chemotherapy. Clin Cancer Res. 2019 Aug 1;25(15):4644-4655. doi: 10.1158/1078- 0432.CCR-19-0173.PMID: 31061067 (* co-senior authors). Clifton GT, Hale D, Vreeland TJ, Hickerson AT, Litton JK, Alatrash G, Murthy GK, Qiao N, Philips AV, Lukas JJ, Holmes JP, Peoples GE, Mittendorf EA. Results of a Randomized Phase III Trial of Nelipepiumut-S + Trastuzumab Versus Trastuzumab to Prevent Recurrence in Patients with High-Risk HER2 Low-Expressing Breast Cancer. Clin Cancer Res. 2020 Jun 1;26(11):2515-2523. doi: 10.1158/1078-0432.CCR-19-2741. PMID: 32071118. Mittendorf EA, Zhang H, Barrios CH, Saiji S, Jung KH, Hegg R, Koehler A, Sohn J, Iwata H, Telli ML, Ferrario C, Punie K, Penault-Llorca F, Patel S, Duc AN, Liste-Hermoso M, Maiya V, Molinero L, Chui SY, Harbeck N. Neoadjuvant Atezolizumab in Combination with Sequential Nab-Paclitaxel and Anthracycline-Based Chemotherapy Versus Placebo and Chemotherapy in Patients with Early-Stage Triple-Negative Breast Cancer (Impassion0310: A Randomized, Double-Blind, Phase 3 Trial). Lancet. 2020 Oct 10;396 (10257):1090-1100. doi: 10.1016/S0140-6736(20)31953-X. PMID: 32966830. Yam C, Yen EY, Chang JT, Bassett RL Jr, Alatrash G, Garber H, Huo L, Yang F, Philips AV, Ding QQ, Lim B, Ueno NT, Kannan K, Sun X, Sun B, Parra Cuentas ER, Symmans WF, White JB, Ravenberg E, Seth S, Guerriero JL, Rauch GM, Damodaran S, Litton JK, Wargo JA, Hortobagyi GN, Futreal A, Wistuba II, Sun R, Moulder SL, Mittendorf EA. Immune Phenotype and Response to Neoadjuvant Therapy in Triple- Negative Breast Cancer. Clin Cancer Res. 2021 Jul 12. doi: 10.1158/1078-0432.CCR-21-0144. Online ahead of print. PMID: 34253579 158

International Mesothelioma Program The International Mesothelioma Program, centered in the Division of Thoracic Surgery, has been in existence for nearly 20 years. It initially focused on clinical activity and patient support, but in parallel has built up a considerable infrastructure for research, collaboration and innovation. Since the 1990s, the team has been prospectively collecting tumor specimens and blood from patients undergoing surgery, and tracking outcomes. Most recently, they developed and populated a complex data infrastructure that connects specimen information with patient data. This allows them to update outcome data and link it with any analysis done for specific tumors, thus overlaying multiple platforms on individual patients and enhancing the ability to innovate. The program has five ongoing projects. • Project I: Continuously funded by an R01 award for 20 years, the program has been working on developing, validating and optimizing molecular tests in order to better stratify patients for treatment and predict outcomes in a more rational manner. As part of this work, they developed an algorithm for predicting outcomes for patients undergoing surgery for mesothelioma, prospectively validated it and provided in a recent publication an online tool to apply to patients. • Project II: The focus of project II has been on sequencing the mesothelioma genome. This began with publication of the first mesothelioma transcriptome, then the genome and progressed with evolving next-gen technologies. In 2016, they published the landmark genetic sequencing analysis of mesothelioma in Nature Genetics, which has been the basis of many follow-up studies, including the Cancer Genome Atlas. They are currently working on a single-cell transcriptomic assessment of the mesothelioma tumor microenvironment. • Project III: This project is part of a Department of Defense-funded multicenter effort to profile tumors obtained from veterans of the U.S. armed forces, to understand why they comprise one- third of patients with mesothelioma in the country. • Project IV: The focus of project IV is to define new treatments based on specific genetic alterations. This has included a prospective phase I-II clinical trial with novel biologic drugs, as well as preclinical studies in cell lines and in mice. • Project V: Project V has focused on the clinical characterization of mesothelioma in general, surgical outcomes, diagnosis, radiographic characterization, as well as special features in subgroups of patients (e.g., women). This work has included collaborations with dozens of other academic centers (Duke, Massachusetts General Hospital, Boston Medical Center, NYU, UCSF, and the universities of Zurich, Western Australia, Toronto and Leicester). The work has been supported by NCI, BIDH and VA intramural funding, as well as through grants via pharmaceutical companies (Genentech, Merck, Verastem, Instill Bio, Epizyme). Exemplary Publications Yeap BY, De Rienzo A, Gill RR, Oster ME, Dao MN, Dao NT, Levy RD, Vermilya K, Gustafson CE, Ovsak G, Richards WG, Bueno R. Mesothelioma Risk Score: A New Prognostic Pretreatment, Clinical-Molecular Algorithm for Malignant Pleural Mesothelioma. J Thorac Oncol. 2021 Nov;16(11):1925-1935. doi: 10.1016/j.jtho.2021.06.014. Epub 2021 Jul 6. PMID: 34242791. 159

Lapidot M, Case AE, Larios D, Gandler HI, Meng C, Tošić I, Weisberg EL, Poitras MJ, Gokhale PC, Paweletz CP, Podar K, Salgia R, Saladi SV, Griffin JD, Frank DA, Bueno R, Sattler M. Inhibitors of the Transcription Factor STAT3 Decrease Growth and Induce Immune Response Genes in Models of Malignant Pleural Mesothelioma (MPM). Cancers (Basel). 2020 Dec 22;13(1):7. doi: 10.3390/cancers13010007. PMID: 33374980. Lapidot M, Case AE, Weisberg EL, Meng C, Walker SR, Garg S, Ni W, Podar K, Hung YP, Carrasco RD, Knott A, Gokhale PC, Sharma S, Pozhitkov A, Kulkarni P, Frank DA, Salgia R, Griffin JD, Saladi SV, Bueno R, Sattler M. Essential Role of the Histone Lysine Demethylase KDM4A in the Biology of Malignant Pleural Mesothelioma (MPM). Br J Cancer. 2021 Aug;125(4):582-592. doi: 10.1038/s41416-021-01441-7. Epub 2021 Jun 4. PMID: 34088988. Lapidot M, Gill RR, Mazzola E, Freyaldenhoven S, Swanson SJ, Jaklitsch MT, Sugarbaker DJ, Bueno R. Pleurectomy Decortication in the Treatment of Malignant Pleural Mesothelioma: Encouraging Results and Novel Prognostic Implications Based on Experience in 355 Consecutive Patients. Ann Surg. 2020 Dec 3. doi: 10.1097/SLA.0000000000004306. Epub ahead of print. PMID: 33278174. De Rienzo A, Chirieac LR, Hung YP, Severson DT, Freyaldenhoven S, Gustafson CE, Dao NT, Meyerovitz CV, Oster ME, Jensen RV, Yeap BY, Bueno R, Richards WG. Large-Scale Analysis of BAP1 Expression Reveals Novel Associations with Clinical and Molecular Features of Malignant Pleural Mesothelioma. J Pathol. 2021 Jan;253(1):68-79. doi: 10.1002/path.5551. Epub 2020 Oct 15. PMID: 32944962. COVID-19 Research in Thoracic Surgery At the beginning of the COVID-19 pandemic, members of the Division of Thoracic Surgery wanted to better understand COVID-19 and develop potential solutions. They embarked on a number of projects to help patients and the institution: • In February 2020, the division anticipated that some patients would require ECMO support and reorganized the ECMO team to strategically care for COVID-19 patients. The team then raised nearly $600,000 in philanthropic funds and bought four additional ECMO devices for the institution. Furthermore, they developed safe methods to manage ECMO for COVID-19 patients and shared the experience with others via publications. • Through existing collaborations with colleagues in Germany, Steve Mentzer, MD, studied lung specimens and helped establish some of the patterns of COVID-19 progression in the lungs. • The team invented and built a new method to filter the effluent and air from chest tubes and Pleurovacs to reduce the risk of viral contamination in the hospital. This device was optimized by the Mass General Brigham COVID task force and research group and was successfully evaluated through a clinical trial of 20 patients at the Brigham. It is now ready for implementation for further use across the system. 160

Exemplary Publications Weiss KD, Coppolino A, Wiener DC, McNamee C, Riviello R, Ng JM, Jaklitsch MT, Marshall MB, Rochefort MM. Controlled Apneic Tracheostomy in Patients with Coronavirus Disease 2019 (COVID-19). JTCVS Tech. 2021 Apr; 6:172-177. doi: 10.1016/j.xjtc.2020.11.016. Epub 2020 Dec 7. PMID: 33319213. Rinewalt D, Coppolino A, Seethala R, Sharma N, Salim A, Keller S, Mallidi HR. COVID-19 Patient Bridged to Recovery with Veno-Venous Extracorporeal Membrane Oxygenation. J Card Surg. 2020 Oct;35(10):2869-2871. doi: 10.1111/jocs.14829. Epub 2020 Jul 15. PMID: 32668041. Dolan DP, Swanson SJ, Lee DN, Polhemus E, Kucukak S, Wiener DC, Bueno R, Wee JO, White A. Esophagectomy for Esophageal Cancer Performed During the Early Phase of the COVID-19 Pandemic. Semin Thorac Cardiovasc Surg. 2021 Jul 1: S1043-0679(21)00303-8. doi: 10.1053/j.semtcvs.2021.06.022. Epub ahead of print. PMID: 34217786. Mislang AR, Soto-Perez-de-Celis E, Russo C, Colloca G, Williams GR, O'Hanlon S, Cooper L, O'Donovan A, Audisio RA, Cheung KL, Sarrió RG, Stauder R, Jaklitsch M, Cairo C, Gil LA Jr, Sattar S, Kantilal K, Loh KP, Lichtman SM, Brain E, Wildiers H, Kanesvaran R, Battisti NML. The SIOG COVID-19 Working Group Recommendations on the Rollout of COVID-19 Vaccines among Older Adults with Cancer. J Geriatr Oncol. 2021 Jun;12(5):848-850. doi: 10.1016/j.jgo.2021.03.003. Epub 2021 Mar 5. PMID: 33715995. Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F, Vanstapel A, Werlein C, Stark H, Tzankov A, Li WW, Li VW, Mentzer SJ, Jonigk D. Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in COVID-19. N Engl J Med. 2020 Jul 9;383(2):120-128. doi: 10.1056/NEJMoa2015432. Epub 2020 May 21. PMID: 32437596. G. JUNIOR FACULTY Development of junior faculty members is a priority for the DOS research leadership. To support these early career investigators, the department has conducted grant writing seminars in collaboration with the departments of surgery at Beth Israel Deaconess Medical Center and Massachusetts General Hospital, established a formal process for mock study sections to review their grant applications and established two internal funding mechanisms. Several of the clinical divisions have established mentoring committees to oversee the early career development of these investigators. Details of the research programs of some of the department’s most promising junior faculty are highlighted below. Regan W. Bergmark, MD Dr. Bergmark is a subspecialized otolaryngologist in rhinology and endoscopic sinonasal and skull base surgery, who practices at the Brigham, Brigham Faulkner Hospital and DFCI. Her focus is on the clinical and surgical care of patients with complex rhinologic disease, ranging from inflammatory sinus disease and complex immunologic disease to cancer. Dr. Bergmark serves as the co-director of the Rhinology Education Curriculum for HMS Otolaryngology. 161

Dr. Bergmark is also a core faculty member at the CSPH. Her research focuses on equitable access to high quality surgical care, with a specific focus on understanding the mechanisms that drive disparities in surgical health care access and outcomes for historically underserved communities. Most recently, she has focused on 1) the surgical workforce composition and geographical distribution; and 2) the role of surgical referral networks in perpetuating the use of lower performing hospitals and lower volume surgeons by patients of low socioeconomic status and racial/ethnic minority backgrounds. Dr. Bergmark has received three grants for this work, has published 50 papers since joining the Brigham faculty in August of 2018 and has given numerous national talks on health equity. Marie Billaud, PhD Dr. Billaud is a PhD investigator whose research focuses on the physiology of small and large blood vessels, with a specific interest in how cardiovascular diseases affect their structure and functions at the organ, cellular and subcellular levels. Dr. Billaud has developed a clinically driven research program in close collaboration with cardiac surgeons exclusively focused on human ascending aortic disease. Despite guidelines recommending “watchful waiting” and surgical aortic replacement of ascending aortic aneurysms to prevent aortic dissection, nearly 20% of patients with aortic dissection die before reaching the hospital, and one of three patients die in the hospital. Dr. Billaud’s published work has introduced new paradigms in ascending aortic aneurysm pathophysiology, including a role for hypoxia and the prospect for progenitor-based regenerative therapies Her current research efforts examine the interplay between cellular metabolism and extracellular matrix remodeling in ascending aortic aneurysm, with a focus on sex differences. Using single-cell and proteomic analyses, she has initiated a comprehensive investigation of the cellular phenotype of men and women aneurysmal specimens and the network pathways underlying the disease. Through these efforts, Dr. Billaud’s work will provide a better understanding of the differences in clinical presentation of ascending aortic disease in men and women, positioning the medical community to provide tailored, sex-based care to these patients. Jennifer L. Guerriero, PhD Dr. Guerriero oversees a translational laboratory in the Division of Breast Surgery that is working to elucidate the biology and mechanistic regulation of tumor-associated macrophages (TAMs) in breast cancer. She and her lab members aim to understand the diversity of TAM subsets, as well as their diverse ontogeny in breast tumors and, ultimately, identify novel strategies to target TAMs for anti- cancer therapy to enhance response to both chemo- and immunotherapy in breast cancer. They have successfully developed and characterized several first-in-class, novel, class IIa HDAC inhibitors (Patent No. 16880073.8-1109) and showed that they induce a switch in TAM phenotype from pro- to anti-tumor and mediated an anti-tumor response in pre-clinical models of breast cancer. They have recently shown that breast tumor cell intrinsic mutations influence the tumor microenvironment, including recruitment of TAMs. They demonstrated that BRCA1 mutations induce high levels of cytosolic DNA, which activates 162

the STING pathway leading to activation of the IFN pathway. PARP inhibitor (PARPi) therapy further enhances this pathway, and the PARPi treated breast cancer cells secrete high levels of CXCL10 and CCL5, which recruit certain types of T-cells and macrophages. This work revealed that the efficacy of PARPi is dependent on cGAS-STING pathway activation and recruitment of CD8 T-cells. This work contributed to the design of a clinical trial evaluating PARPi plus immune checkpoint blockade (ICB; to further activate T-cells) that was included in the recently renewed Dana-Farber Breast Cancer Program SPORE Award. Dr. Guerriero is an investigator on the SPORE and serves as the translational PI on that trial investigating PARPi plus ICB (DFCI 20-371; PI: Mayer). More recently, Dr. Guerriero’s lab identified that TAMs are the predominant white blood cell in BRCA- associated tumors both before and after PARPi, and that PARPi directly regulate macrophage phenotype function and metabolic signaling. Importantly, they found that PARPi-treated macrophages inhibited T- cell function and activation, which limited PARPi responses. They identified a novel strategy to overcome PARPi resistance through pharmacological targeting of macrophages (Mehta et al. Nature Cancer 2021). This work reveals a previously unknown mechanism of PARPi resistance and lays the groundwork for future clinical trials to enhance PARPi plus ICB by targeting macrophages. Christina A. Minami, MD Dr. Minami’s research efforts focus on decision-making, treatment patterns and outcomes in older women with early-stage breast cancer. She currently has three ongoing SEER-Medicare analyses addressing variations in care for these patients, in addition to two National Cancer Database analyses examining hospital-level factors associated with axillary surgery use and time to treatment in this population. Dr. Minami also has three qualitative projects that examine patient and physician attitudes toward omission of axillary surgery, as well as one that will be using discourse analysis to study the content of treatment conversations among surgical, medical and radiation oncologists and older women with early-stage breast cancer. She is also starting a clinical initiative to perform geriatric screening in all patients evaluated by the breast surgical oncologists at the Longwood campus of Dana-Farber Cancer Institute (DFCI), with an accompanying evaluation to understand how this data impacts treatment conversations and decision-making. During the height of the pandemic, Dr. Minami also carried out several COVID-related projects in cancer patients, including a retrospective analysis evaluating outcomes in cancer patients with a prolonged time to surgery and a qualitative analysis of our own breast and prostate cancer patients treated at DFCI who suffered COVID-related surgical delays. George Molina, MD, MPH Dr. Molina’s current research focuses on health systems innovation in pursuit of safety, quality and equity in surgical care. Specifically, he is interested in understanding and addressing the barriers to receiving surgical treatment for colorectal liver metastasis. His overall career objective is to reduce the variation in surgical treatment of colorectal cancer liver metastasis locally, regionally and nationally. 163

Colon cancer is one of the most common cancers and a large proportion of these patients will develop liver metastasis. According to the National Comprehensive Cancer Network Guidelines, patients with resectable liver metastasis from colorectal cancer should be offered a curative liver resection. Despite this recommendation, previous research has shown that surgical treatment for colorectal cancer liver metastasis is underutilized. Dr. Molina’s research efforts have included evaluating the association among race, hospital volume of major liver surgery and access to metastasectomy for colorectal liver metastases (selected for an oral presentation at the 2021 Americas Hepato-Pancreato-Biliary Association meeting); and evaluating the association between likelihood of undergoing liver metastasectomy and seeking care from more than one Commission on Cancer hospital for colorectal liver metastasis. Indranil Sinha, MD Dr. Sinha’s research focuses on skeletal muscle regeneration, both in the settings of aging and trauma. As a surgical resident, he was awarded an F32 from the National Institutes of Health to spend two dedicated research years at the Harvard Stem Cell Institute in the laboratory of Dr. Amy Wagers. There, Dr. Sinha learned how aging limits muscle stem cell regeneration and how this can lead to muscle loss. When Dr. Sinha completed his residency, he began a research laboratory focused on promoting and improving functional recovery in aging and trauma, two situations which severely limit muscle regeneration. His initial work, funded by the Boston Claude D. Pepper Older Americans Independence Center, found that hypoxia signaling, which regulates many processes in the body, decreases dramatically in aging muscle and contributes to loss of muscle regeneration. This finding led to Dr. Sinha being awarded a K76 as a Beeson Scholar and emerging leader in aging research from the National Institute of Aging. He is currently focused on how hypoxia signaling factors are differentially regulated by aging and how these changes impact muscle mass, function and response to exercise in the elderly. Ultimately, the goal is to develop pharmacotherapies that can target aging-associated loss of muscle mass. Dr. Sinha also collaborates with bioengineers to promote functional recovery following traumatic muscle injury. Normally, these injuries heal with scar and not functional muscle tissue, greatly limiting recovery and muscle function. His work focuses on using scaffolds impregnated with growth factors and stem cells to allow for muscle tissue regeneration, rather than scar formation. He is a co-investigator on three National Institutes of Health R01s regarding tissue regenerative strategies for traumatic muscle loss. Thomas Tsai, MD, MPH Dr. Tsai’s research focuses on generating rapid empirical evidence to guide effective public health and public policy interventions. By leveraging national claims, health system and population health datasets, he studies the effectiveness and unintended consequences of health policy interventions on the affordability, accessibility, quality and equity of health care in the United States. His work currently 164

focuses on three core areas: 1) evaluation of Medicare alternative payment models; 2) the role of hospital mergers and health systems in increasing health care value by site of care optimization; and 3) COVID-19 public health and policy response. Dr. Tsai’s Medicare projects are focused on payment and delivery system reform to improve health care value. Using Medicare Advantage encounter data, he is assessing rates of low-value care and variations in quality of care in beneficiaries enrolled in Medicare Advantage versus traditional Medicare. He is currently designing a study to evaluate the Centers for Medicare & Medicaid Services Hospital Without Walls waiver programs initiated during the COVID-19 pandemic. Dr. Tsai is also leading a randomized controlled trial of a surgical home hospital for bariatric surgery patients at the Brigham. From the standpoint of hospital mergers and health systems, Dr. Tsai is completing a project using Medicare claims to assess the effect of rural hospital mergers on patient outcomes and hospital financial performance. He is also collaborating with a team of researchers from Harvard Business School to merge U.S. Census data on hospital management with hospital discharge data, to assess whether hospitals with better management performance were associated with improved outcomes during the COVID-19 pandemic. During the pandemic, Dr. Tsai led policy development at the Harvard Global Health Institute to provide guidance on public health policy for local, state and federal agencies. As part of this effort, he has: • generated national and state testing targets in collaboration with NPR • published estimates of hospital capacity in collaboration with The New York Times • developed a COVID vaccination dashboard in collaboration with Microsoft AI for Health • developed the Google-Harvard COVID-19 Public Forecast model in collaboration with Google Cloud • evaluated the relationship between internet symptom search queries and COVID-19 case growth with Google Health. 165

Bruce A. Beal and Robert L. Beal Surgical Fellow In 2020 the Department of Surgery, supported by a generous philanthropic gift from Bruce and Robert Beal, created the Beal Surgical Fellow program to further support the research efforts of junior investigators. All faculty members at the rank of instructor or assistant professor are eligible to submit grant applications that undergo peer review by the department’s Research Oversight Committee. A description of the recipients to date and their supported projects are detailed below. 2020 - Eric Sheu, MD, PhD, and James Yoo, MD Emerging evidence suggests that one unrecognized effect of bariatric surgery is a potential association with increased risk of colorectal cancer (CRC). Therefore, a key question remains unanswered: What are the biologic effects of bariatric surgery on the development of CRC? Recent attempts to answer this question have been observational or retrospective, yielding an array of mixed results. A persistent obstacle in this endeavor has been the lack of fundamental understanding that would place obesity and bariatric surgery in their proper physiologic context vis-à-vis CRC pathogenesis. As the burden of obesity and CRC continues to rise, particularly in young patients and patients of color, so has the urgency of addressing this unmet need. Recent efforts to gain mechanistic clarity have identified several potential biological pathways linking obesity and bariatric surgery with intestinal inflammation and colorectal carcinogenesis. Of those, the colonic microbiome has emerged as a compelling intermediary linking these processes. This research collaboration has focused on how sleeve gastrectomy-induced alterations in the colonic microbiome may regulate the development of inflammation-associated cancer, a particularly aggressive variant of CRC. Utilizing a murine sleeve gastrectomy (SG) model in combination with the well-validated azoxymethane- dextran sulfate sodium (AOM-DSS) model of inflammation-associated cancer, they found that the post- SG microbiome is characterized by enrichment of key colitogenic microbial taxa, which exacerbates colonic inflammation and plays a causal role in inflammation-associated CRC. Specifically, following SG there was a greater than four-fold increase in CRC after exposure to AOM-DSS. Strikingly, microbiota transplant from SG mice into germ-free mice independently led to a nearly five-fold increase in CRC compared to sham mice. These findings reveal a novel, microbially-driven mechanism of colorectal carcinogenesis that may allow for CRC risk prediction and modification through highly personalized prevention strategies. 2021 - Shailesh Agarwal, MD Dr. Agarwal’s laboratory is innovating new technology with translational potential using patients’ fat tissue. His team has developed a strategy for isolating a patient’s adipocytes from fat tissue in a resource-restricted environment, such as the operating room. They are able to perform point-of-care gene delivery to enable these adipocytes to express and secrete therapeutic peptides, as well as human (and mouse) adipocytes to express anti-fibrotic peptides, including inhibitors of the pro-fibrotic transforming growth factor-beta signaling cascade. Their strategy utilizing adipocytes presents a substantial advantage over alternative strategies for peptide delivery. First, these adipocytes synthesize and secrete the desired peptide; therefore, these strategies obviate ex vivo peptide manufacturing, 166

formulation and delivery. Furthermore, adipocytes can be delivered throughout the body in various anatomic sites, allowing for directed drug delivery beyond traditional scaffolds. Finally, these adipocytes can be programmed using transcriptional networks to regulate expression; therefore, how much of the desired peptide is released and when it is released can be controlled. Because adipocytes are abundant in most patients, they can be harvested and do not require in vitro expansion. As a result, genetically modified adipocytes can be redelivered into the patient as autologous adipocyte bioreactors, which enable endogenous peptide production and secretion. They are testing these adipocytes in several mouse models of disease and tissue injury; positive findings from these studies will inform the development of large-animal studies en-route to clinical translation. 2021 - Christina A. Minami, MD With the aging of the U.S. population comes a growing interest in how age and age-related syndromes alter cancer outcomes, and how cancer treatments themselves may change the trajectory of aging. Frailty, a condition that becomes increasingly prevalent with advancing age, is characterized by decreased physiologic reserves, loss of adaptive capacity and increased vulnerability to stressors. In older patients with breast cancer present with ductal carcinoma in situ (DCIS) or early-stage, hormone receptor-positive (HR+) disease, chemotherapy has limited benefits, leaving locoregional therapy as the mainstay of treatment. Standard locoregional therapy for early-stage breast cancer includes: 1) surgery consisting of mastectomy or breast-conserving surgery (BCS); 2) axillary evaluation, which can refer to either axillary lymph node dissection (ALND) or sentinel lymph node biopsy (SLNB) – the latter of which is considered the current standard of care in early-stage disease; and 3) radiation therapy (RT) if BCS is pursued. Although these treatments are not without morbidity (e.g., seroma, hematoma, infection, skin toxicities, second malignancies), surgery and RT for breast cancer is thought to have relatively low rates of postoperative and treatment-related complications. Recent data, however, has demonstrated that cancer diagnosis serves as an inflection point in frailty trajectory over time, reflecting an acceleration of worsening frailty over time. The extent to which these locoregional treatments may significantly contribute to worsening frailty, thus rendering patients more susceptible to other stressors down the line, remains unclear. The ramifications of cancer treatment itself are important to understand, especially given the low disease-specific mortality rates currently documented (4.1% five-year breast cancer-specific mortality in women over 85 years of age with stage I disease). Thus, the objective of Dr. Minami’s project is to determine the prevalence of and factors associated with sustained or worsening frailty in older adults undergoing locoregional therapy for DCIS and stage I HR+ breast cancer using SEER-Medicare data between 2010 and 2015. Dr. Minami postulated that older age (over 80 years of age), pre-frail status prior to treatment (compared to robust status), undergoing mastectomy rather than lumpectomy, and the addition of RT, will be significantly associated with sustained or worsening frailty. 167

Junior Fellowship in Honor of Robert T. Osteen, MD (Osteen Fellowship) Established in 2016 as part of the Harvard Medical School Office for Faculty Affairs Shore Program, the Osteen Fellowship supports the research of a junior faculty member in the Brigham Department of Surgery. 2017 - Gita Mody, MD, MPH Dr. Mody used the support of the Osteen Award to complete a project in collaboration with thoracic surgeons in Latin America as part of a longstanding relationship among the Peruvian Ministry of Health, the non-governmental medical volunteer organization, Partners in Health, and its sister organization Socios En Salud. The project focused on outcomes of pulmonary resection for patients with multi-drug resistant tuberculosis. Patients with tuberculosis have been treated in a multidisciplinary fashion for more than 20 years. Around the time Dr. Mody began her work, there was increasing awareness and concern for transmission of tuberculosis to health care workers, therefore surgical services for patients with tuberculosis were curtailed. Working with an infectious disease physician and a pulmonologist from the Brigham, an epidemiologist from Harvard Medical School and thoracic surgeons from Hipolito Unanue National Hospital in Lima, Peru, Dr. Mody served as an advisor for the redesign of the operating room and postoperative wards. As part of the process, the team identified clinical research questions for patients requiring pulmonary resection for tuberculosis, including how to improve outcomes and the referral process leading to additional lines of investigation. Findings from her investigations detailing the referral process for surgical management of tuberculosis in Lima have been published in the Journal of Surgical Research (2021). 2018 - Matthew A. Nehs, MD Dr. Nehs’ Osteen Award was granted for his proposal in studying the metabolism and therapeutics for anaplastic thyroid cancer. It came at a critical juncture in funding for his lab, and it paved the way for numerous abstracts and presentations resulting from this grant. In short, they studied the effects of glucose metabolism and the ketogenic diet (KD) on tumor growth in anaplastic thyroid cancer (ATC). They found that ATC was sensitive to glucose as a substrate and that KD was as an effective adjunct in a mouse model when combined with other metabolic inhibitors. These experiments led to the development of a diabetic mouse model of ATC and to antidiabetic metabolic therapy as an adjunctive treatment. The data that was generated from the Osteen Award helped pave the way for successfully obtaining the Thyroid Cancer Survivors Network Research Grant in 2019. To date, the Nehs Lab has two publications (Surgery 2020, Surgery 2021) and eight abstracts that were directly attributable to this year of funding, and many other publications are in preparation from experiments that built on this work. Moreover, the Osteen Award provided important funding not just for Dr. Nehs, but also for the laboratory fellows and research assistants in his lab during that time. One of his research fellows, Bixiao Zhao, MD, a general surgery resident, had the opportunity to present the Osteen-supported work as podium presentations at multiple local, state and national meetings. 168

2019 - Anna C. Weiss, MD Dr. Weiss used funding from her Osteen Award to assemble the necessary study team and activate the Genetic Testing for All Breast Cancer Patients (GET FACTS) trial. GET FACTS is a randomized clinical trial assessing two forms of risk counseling for newly diagnosed unilateral breast cancer patients who receive panel gene testing. She developed GET FACTS in response to the critical need to determine the optimal genetic counseling strategy for these patients. Routine multigene panel testing combined with expanded testing practices has led to the identification of many more women with hereditary breast cancer predisposition, yet uncertainties remain about the impact of these practices on surgical decision- making. In fact, there is evidence that the act of genetic testing leads to increased use of contralateral prophylactic mastectomy (CPM), even among patients with negative results. The two randomization arms of GET FACTS include standard genetic counseling and quantitative counseling, in which patients are provided with their personal risk of contralateral breast cancer (CBC). The objectives of GET FACTS are to: 1) determine patients’ assessments of their own CBC risk by counseling method; 2) compare patients’ propensities to undergo CPM by counseling method; and 3) measure CPM rates by counseling method. The hypothesis is that including patients’ specific CBC risks in their pre-surgical risk counseling will lead to more accurate personal risk assessment and lower CPM rates. At completion of this proposed work, the expected outcome is to identify a counseling strategy that will allow patients to make informed surgical treatment decisions. Since activation in June 2020, more than 150 patients have been enrolled in GET FACTS. Dr. Weiss anticipates the trial will be complete within the next two years. She has subsequently been awarded additional internal funding for the GET FACTS trial, including a Friends of DFCI Grant and the Susan F. Smith Center for Women’s Cancers Breast & Gynecologic Cancer Innovation Award. 2020 - Erika Rangel, MD Dr. Rangel’s Osteen project focused on the impact of pregnancy complications and infertility in female surgeons on burnout and attrition. Surgeons often struggle to integrate professional and personal obligations, which leads to increased risk of career dissatisfaction, burnout and attrition. Given the difficulties of childbearing during residency, most women surgeons delay pregnancy until after completion of training, when the risks of adverse pregnancy outcomes and infertility rise sharply, in the mid-30s. Using a national sample of surgeons, this project examined risks of infertility and pregnancy complications among female surgeons to determine perceptions of workplace support for these challenges, and to assess how these adverse outcomes and workplace support for them may impact career satisfaction and burnout. An IRB-approved, self-administered survey that used validated questionnaires was completed by 1,175 surgeons, and 850 met inclusion criteria. Among the key findings were: • compared with female non-surgeon partners of male surgeons, female surgeons were more likely to have major pregnancy complications (48.3% vs. 27.2%; p<0.001), which was significant 169

after controlling for maternal age, work hours, in vitro fertilization use and multiple gestation (OR 1.72;95% CI: 1.11-2.66) • compared to male surgeons, female surgeons are more likely to delay having children because of surgical training (65.0% vs. 43.7%, p<0.001), have fewer children (mean [SD]:1.8 [0.8] vs. 2.3 [1.1]; p<0.001) and are more likely to use assisted reproductive technology (24.9% vs. 17.1%; p=0.04) • female surgeons had higher rates of postpartum depression than female non-surgeon partners of male surgeons (11.1% vs. 5.7%). This work was presented as the 2021 Presidential Address of the Association for Academic Surgery annual meeting and subsequently published in JAMA Surgery. The findings were used as preliminary data for a subsequent grant application submitted to the Association of Women Surgeons. 2021 - Jennifer Guerriero, PhD The most recent recipient of the Osteen Award was Dr. Guerriero in support of her project entitled, “Elucidating Mechanisms of Immune Evasion in Hormone-Receptor Positive (HR+) Breast Cancer.” Immunotherapy, which activates T-cells to fight tumors, is now a pillar of cancer care. Unfortunately, HR+ breast cancer has shown minimal response in multiple trials investigating immunotherapy. HR+ breast cancer accounts for roughly 70% of breast cancer cases, and even with optimal therapy, HR+ breast cancer patients have a lifelong risk of recurrence. Therefore, new treatment strategies are urgently needed. It has been well documented that there are limited T-cells in HR+ breast cancer, which is likely a major factor related to dismal responses to immunotherapy. Dr. Guerriero’s study seeks to uncover the mechanisms that prevent recruitment of T-cells into HR+ breast cancers and to inform opportunities for novel immunotherapy-based therapeutic strategies. H. RESIDENT RESEARCH Most residents completing their surgical training in the Brigham Department of Surgery spend two years dedicated to scholarly activity. The work completed by trainees spans a broad spectrum of research, from health services and public policy, to work evaluating the clinical care of surgical patients, to laboratory-based investigations. Based on their interests, residents have the choice to complete their academic time at the Brigham, at other institutions within the city of Boston or at remote sites. Under the direction of Mark Fairweather, MD, associate program director, residents begin considering different research opportunities during their intern year to facilitate a productive research experience. Dr. Fairweather guides residents through the process of identifying areas of interest and potential mentors. Critical aspects of the dedicated research time are to learn the scientific method, learn how to write competitive grant applications, and develop skills in communicating scientific findings through verbal and written communication. In 2020, to assist residents in gaining skills in grant writing, the department began hosting a grant- writing workshop, with a specific focus on F32 applications. Modeled after an F32 grant, the Hale Fellow 170

Award was recently established, with the first award to be presented in 2022. All residents will be required to apply, which will allow senior faculty to provide feedback that can be incorporated by the residents into subsequent applications. The department has also identified a grants administrator, who focuses on assisting residents with their grant applications. The department has two mechanisms to recognize residents for excellence in research: The Mannick Award and the Magnificent 7 Award. Examples of resident research activity during the 2020-2021 academic year are listed below. Exhibit 21: General Surgery Resident Research (2020-2021) Name Position/Location Research Focus Rachel Atkinson, MD Research Fellow, BWH CSPH Participated in the Provider Awareness and Cultural dexterity Toolkit for Surgeons (PACTS) trial: Sourav Bose, MD Research Fellow, Center for Fetal Research, Children's • Investigates impact of a novel surgical education Hospital of Philadelphia; curriculum for residents on outcomes for culturally Associate Fellow, Leonard diverse patients. Davis Institute of Health Economics • Other projects: Gender equity and reproductive challenges amongst surgeons. • Developing and implementing in utero gene therapy in small animal models of multiple diseases of the fetus. • Designing and implementing a mixed-methods study exploring the financial, clinical and intangible benefits of integrated care in children with thoracic disease. Samuel Enumah, MD Clinical Research Resident • Exploring the impacts of health policy on hospital-level James Etheridge, MD Scholar, Association for and patient-level spending in the delivery of surgical care. Frances Hu, MD Academic Surgery; NIH T32 Fellow, Research • Addressing the “know-do gap” to ensure all patients have Training in Alimentary Tract access to high-quality evidence-based surgical care. Surgery, Massachusetts General Hospital • Studying structured care processes such as clinical Safe Surgery/Safe Systems pathways. Research Fellow, Ariadne Labs; Postdoctoral Research • Implementing safety checklists. Fellow, Harvard T.H. Chan • Expanding Superior Surgical and Trauma Care for Elders School of Public Health Pathway (SSTEP) and evaluating its implementation Research Fellow, BWH CSPH through a research framework. • Examining ways to improve coordination of geriatric and palliative care for surgical patients. 171

Joshua Jolissaint, MD Hepatopancreatobiliary • Clinical and tissue-based translational research to study Research Fellow, Memorial intrahepatic cholangiocarcinoma, pancreatic cancer and Abby Larson, MD Sloan Kettering Cancer colorectal cancer. Center James Luo, MD • Treatment and genomic stratification of outcomes for Paige Newell, MD Research Fellow, Center for intrahepatic cholangiocarcinoma. Jason Pradarelli, MD, Fetal Research, Children's MS Hospital of Philadelphia • Use of radiation for locoregional control in pancreatic Laura Piechura, MD cancer. NIH T32 Research Fellow, Lily Saadat, MD BWH Laboratory for • Role of tumor-derived exosomes in multiple cancer types. Vanessa Welten, MD, Surgical and Metabolic • Master’s in clinical and translational investigation through MPH Research Vicky and Joseph Safra Weill Cornell Medical College funded by NIH/NCATS. Cardiac Surgery Clinical • Fetal development of the lung, heart, and brain in CDH Research Fellow; BWH CSPH Research Fellow and how these organ systems interact in utero via conventional Doppler ultrasound, contrast enhanced Safe Surgery Fellow, ultrasound (CEUS) and tissue elastography. Ariadne Labs • Novel pumpless ECMO system and the utility of perflurocarbon (PFC) ventilation in promoting Research Fellow, BWH oxygenation and lung recruitment to support severe Division of Thoracic Surgery postnatal CDH. • Metabolic effects of obesity and gut microbiome on Clinical Research Fellow, gastrointestinal cancer pathogenesis. Memorial Sloan Kettering • How a modified gut microbiome induced by obesity and Cancer Center bariatric surgery impacts colorectal tumor development. Research Fellow, BWH • Clinical outcomes of aortic and valvular surgery. Center for Surgery and • Evolution of socioeconomic disparities in cardiac surgery. Public Health • Surgical coaching: Implementing and studying strategies for practicing surgeons to improve intraoperative performance throughout their careers. • New device safety: Implementing team-based communication practices when new surgical devices enter practice. • Mechanisms related to pulmonary edema formation and primary graft dysfunction in a small-animal model of ex vivo lung perfusion to provide insight into measures for improving donor organ supply and patient outcomes following transplantation. • Evaluation of outcomes after surgery for hepatopancreatobiliary malignancies, with a particular focus on health system variability. • Development of a clinical trial for patients with borderline resectable and locally advanced pancreatic adenocarcinoma. • Colorectal cancer outcomes through quantitative, qualitative and mixed methods approaches. 172

Elizabeth Yates, MD Research Fellow, CSPH; • Developing a decision support tool for patients to MPH Student, Harvard T.H. promote patient-centered care and shared decision- Bixiao (Brian) Zhao, Chan School of Public making in the treatment of rectal cancer. MD Health • Examining the interface between surgery, sustainability T32 Fellow, BWH Nehs and climate change. Laboratory • Unpacking the role of surgeons in the broader climate crisis and its reciprocal impact on surgical patients. • The effects of various metabolic therapies on the growth and progression of anaplastic and poorly differentiated thyroid cancer to develop new adjuvant treatments. I. CURRENT CHALLENGES There are several potential challenges surrounding the attainment of our future goals. Perhaps the most significant is that surgeons who are clinically busy find it difficult to focus time and effort on research. In addition, the structure of the compensation plan, while fair, does not compensate for the time needed to write and submit grants; rather, the compensation plan allows faculty to “buy” non-clinical time by securing grants. Given the current funding environment, it may take an investigator several resubmissions before a grant is accepted for funding, and while the department supports this time through start-up packages and funded research time for an initial period (typically 20-40% for 3 years), that project-development time is scarce beyond the new member period. “Bridge funding” would allow select investigators to protect effort dedicated to writing and submitting competitive applications. It is also difficult for junior faculty to transition from their initial contract onto the compensation plan. Physical space is another challenge, as the institution has limited available wet and dry lab space. We need to optimize density to be good stewards, thereby justifying the need for space when requested. Finally, funding of the departmental core research infrastructure will be a challenge, particularly as we consider investments to improve the support offered to our investigators: increasing shared resources for laboratory investigators and expanding our ability to conduct clinical trials. However, there may be an opportunity to generate philanthropic support, and/or investigate innovative funding models, such as industry partnerships for biospecimen collection and data sharing. J. FUTURE GOALS Advancing scientific discovery by conducting impactful research remains a priority for the DOS. The goals over the next several years are focused on continuing to grow the DOS central research infrastructure to enhance the support of department faculty members engaged in scientific investigation. Specific areas of focus include: • Laboratory Investigation: Goals include continuing to work with institutional leadership to secure appropriate and adequate laboratory space for DOS investigators. In addition, we will work to acquire and maintain shared equipment to be used by all DOS lab teams. 173

• Clinical Research: To enhance clinical research, we will further integrate our newly hired senior clinical research manager into central research processes, to assist departmental investigators with the regulatory and financial aspects of conducting clinical research at the Brigham. In addition, we will expand the responsibilities of our senior clinical research manager to oversee research assistants (RA) in various divisions. For divisions who do not have a large enough footprint to require one full-time equivalent RA, we aim to establish a departmental pool of RAs that could be used by investigators to conduct their studies. Furthermore, we recognize the need to expand access to statistical support for the design and conduct of clinical research studies. • Junior Investigators: We are cognizant of the challenges faced by junior investigators working to establish independent research careers. As detailed in this report, we have increased internal funding opportunities for these investigators and enhanced pre- and post-award support. To further support junior faculty members as well as residents, we are working to establish a grant review committee comprised of senior faculty members. This committee would provide review and feedback on grant applications. • Multi-Investigator Awards: The DOS research program has stretch goals to include support of multi-investigator awards, such as T32 grants and program project grants. This work will be done collaboratively between investigators within the Brigham DOS, as well as with colleagues in other departments at the Brigham and other institutions, including Massachusetts General Hospital. 174

Surgical Education A. OVERVIEW AND ORGANIZATION Education is one of the core missions in the Department of Surgery at Brigham and Women’s Hospital. For over a century, we have been training medical students, residents and fellows in all aspects of surgery. Our faculty are national and international leaders in their field, and they impart their knowledge and expertise locally to our highly talented trainees. After their training, many of our graduates go on to become leaders in academic surgery, both domestically and internationally. The flagship of our training programs is the general surgery residency. Since the Peter Bent Brigham Hospital opened in 1913, general surgery residents have played an integral role in the care of our surgical patients, and in turn, they have received the most cutting-edge surgical training. Our General Surgery Residency Program remains one of the most highly respected training programs in the country. Each year we recruit the best and brightest medical school graduates from across the country to fill our nine available positions. Within this cadre of highly qualified individuals, we are proud to continually recruit a diverse class of trainees, year after year. The education programs are led by Douglas Smink, MD, MPH, the vice chair for Education; the surgical division chiefs; the residency program directors and associate program directors; the student clerkship course directors and associates; the elective student course directors; and the fellowship program directors. All teaching faculty in the department are appointed to the faculty of Harvard Medical School. The department offers six residency programs and 16 fellowships. In addition to the General Surgery Residency Program, other ACGME-accredited programs within the department include: • Cardiothoracic Surgery Integrated Residency • Urology Residency • Thoracic Surgery Residency • Colorectal Surgery Fellowship • Complex General Surgical Oncology Fellowship • Surgical Critical Care Fellowship • Vascular Surgery Fellowship Institutional oversight for graduate medical education at Brigham and Women's Hospital and Massachusetts General Hospital is under the direction of the Mass General Brigham Graduate Medical Education (MGB GME) Office. Each of the two hospitals also have their own education committees that work closely with MGB GME to oversee residency and fellowship programs and medical student education at their respective hospitals. Within the past five years, each residency program in the 175

department has been reviewed annually by the ACGME. The MGB GME Committee also requires an institutional internal review process each year. B. EDUCATION LEADERSHIP Vice Chair for Education Dr. Smink was appointed as the vice chair for Education for the Department of Surgery in 2014 under the leadership of the previous chairman, Michael Zinner, MD, and reappointed in 2017 under Dr. Doherty’s new open process. He has extensive experience and knowledge in surgical education and has held numerous national positions on surgery education boards and councils. He currently serves as the president of the Association of Program Directors in Surgery (APDS), a national association founded in 1977 to maintain high standards of surgical residency training by improving graduate surgical education and patient care. Dr. Smink also served as the associate program director and subsequently the program director of the general surgery Douglas S. Smink, MD, MPH residency for 10 years. Dr. Smink oversees all functions and operations of the Brigham fellowship, residency and student programs, as well as the Surgery Education Office. Surgery Education Office The Surgery Education Office director and staff report directly to the vice chair for Education regarding educational issues common to all residency and student programs within the department, and to the respective program directors of each residency and fellowship program, as well as to the student clerkship course director on issues regarding their individual programs. The education office maintains resident personnel records and provides administrative support for record keeping tasks, including scheduling of resident rotations and teaching conferences; preparing the residency program budget and payroll; processing loan deferrals and verifications of resident training; organizing resident and student orientations; and assisting with the organization of oral exams and annual in-training exams. The education office director also works closely with the program directors, department chair, hospital administration, the GME office and the Mass General Brigham legal counsel in coordinating activities relating to resident disciplinary issues. The Surgery Education Office also provides centralized residency support for the programs in colorectal surgery, general surgery, surgical critical care and vascular surgery; works with specialty coordinators in the divisions of Oral Medicine, Plastic and Reconstructive Surgery, Surgical Oncology, Thoracic and Cardiac Surgery, and Urology, to provide overall central support; and serves as a resource for all payroll, human resources and education-related issues, as well as a clearinghouse for all residencies and fellowships. 176

Serving as the departmental liaison to the various matching programs (ERAS, NRMP and the surgical specialty matches), the education office staff compiles and maintains residency applications and provides support for all phases of the residency selection and interview process for all residency and fellowship programs. With each of the departmental residency programs holding from one to three group interview sessions (depending upon the size of the residency), the education office organizes up to 10 large group interviews per year, either virtually or in person. C. MAJOR ACCOMPLISHMENTS Our education leaders and our department strive to be on the forefront of innovation in surgical education. We have accomplished this through leading and participating in educational research, and by developing new initiatives within our training programs. These initiatives and research projects have focused on the most challenging issues in surgical education today, including topics like assessment, non-technical skills, competency, disparities and workforce issues. Over the past five years, in pursuit of Dr. Doherty’s vision to enhance all academic aspects of the department, considerable investments of time and resources have been made into our education programs. Developments include the establishment of senior faculty member leadership for all training programs, a department education committee, establishment of an education innovation office and an increased awareness of faculty educational responsibilities. Along with incentives, these changes have all had great impact on our already strong and thriving programs. Departmental Educational Accomplishments • Created a department-wide Education Committee, which meets five times per year and includes all student, residency and program directors, as well as resident representatives, to discuss and steer all department-wide educational activity and action. • Held a department-wide Faculty Education Retreat in September 2018, which was an overwhelming success. The department chair closed the ORs for the day, allowing 113 faculty members and 15 chief residents and fellows to attend. After a keynote address by Steven Stain, MD, the former chair of the Residency Review Committee-Surgery, the attendees divided into breakout groups. These groups were assigned to one of the 10 most pressing educational topics for the department. • Established a new Office of Professional Development, based on feedback from the retreat. This office focuses on personal well-being, community and collegiality, enjoyment of work life, and career development and education. Led by Jennifer Shin, MD, SM, vice chair for Faculty Development, this office is supported by a full-time manager. They have sponsored many events to support the faculty, including interest groups, workgroups for OR culture, networking dinners, mentorship opportunities and professional lectures. • Hired Jamie Robertson, PhD, MPH, as the director of Innovation in Surgical Education in 2019. Dr. Robertson has specific responsibility for the development of innovative educational programs offered by and within the department. She has been integral in the following areas: 177

o Learning environment o Curriculum/program development, including new initiatives in curricula, feedback and evaluation tools o Faculty development, including workshops, teaching strategies and mentorship o Education research • Standardized the expectations and support for participation in educational activities. Base expectations for faculty participation were established. Support for time spent in educational leadership or administrative roles were harmonized to reflect the opportunity cost of this work. Incentivized participation in education by linking this to access to additional reimbursement funds for faculty members continuing education expenses. • Hired Jamie Robertson, PhD, MPH, as the director of Innovation in Surgical Education in 2019. Dr. Robertson has specific responsibility for the development of innovative educational programs offered by and within the department. She has been integral in the following areas: • Created a fellowship lecture series under the leadership of Olga Kantor, MD, MS, from the Division of Breast Surgery. Topics include: How to find a job/market yourself in the fall, contract negotiation in the winter, how to transition into practice in the spring and the logistics of practice. General Surgery Residency Accomplishments • Added two additional associate program directors to the leadership team: Naomi Shimizu, MD, associate program director for Wellness and Diversity; and Mark Fairweather, MD, associate program director for Curriculum Development and Research. • Participated in the Flexibility in Surgical Training project and increased elective time for senior residents, to enable them to enhance connection with their mentors and gain deeper experience in their future clinical area of expertise. • Created a new transportation policy in recognition of the role of fatigue on safety and wanting to ensure that residents have a safe ride home following long shifts. Each resident has an Uber account to use if they are post-call (24-hour) or on a shift that ends after 10 pm. If a resident leaves their car at the hospital and they take an Uber home post-call, they can use the residency Uber account to get back to work for their next shift. This initiative covers all post 24-hour shifts and includes affiliate hospitals. • Created the position of chief resident for Diversity, Equity and Inclusion, who oversees all residency diversity actions and events. • Partnered with the MGH surgery residency to create the Mass General Brigham Inclusion, Diversity and Equity Alliance (IDEAL), which created a mission statement and hosts quarterly meetings and social events. • Created a resident crowd-sourced mission statement by which each resident strives to abide. 178

Brigham and Women’s General Surgery Residency Mission Statement The central goal of the Brigham and Women’s Hospital General Surgery Residency is to provide trainees with the skills and experiences to be future leaders in surgery. Achieving these goals requires a collaborative environment in which each resident’s development is fostered by her/his fellow residents. As Brigham general surgery residents, we will (1) strive for excellence in patient care, (2) achieve the highest level of professionalism, (3) prioritize our education, (4) develop ourselves as leaders, (5) foster a culture of respect and (6) care for our community. Patient care. We are a team working in concert to provide outstanding care to all patients that we encounter. Professionalism. As individuals who bring a rich diversity of personal experiences to their training, Brigham residents set high standards for themselves, fellow residents and faculty. These high standards are rewarded with commensurate autonomy and responsibility. Education. Education is of paramount importance in our residency. We invest in the development of each other’s clinical, technical, educational and leadership skills. Leadership. As future academic surgeons, we strive to gain the expertise to become the future leaders in surgery through research, innovation, scholarship, policy and advocacy. Respect. We show respect in our words and actions. We expect this from all members of our community. Community. The Brigham residency relies on effective team-wide collaboration. All members of the community respect our patients and one another. We value the contributions to our team made by physician assistants, nurses, medical students and ancillary staff. Surgery Education Research Accomplishments • Dr. Smink and Steven Yule, PhD, focused on Non-Technical Skills for Surgeons (NOTSS) and partnered with the American College of Surgeons to adapt this teaching and assessment tool for the United States. • Erika Rangel, MD, MPH, has led a research team focused on the impact of maternity and paternity in surgical residency. This work has been widely published and has contributed to important changes of the family leave policy by the American Board of Surgery. • Dr. Smink and Adil Haider, MD, have led an NIH-funded R01 grant, the Provider Awareness and Cultural Dexterity Toolkit for Surgeons (PACTS) Trial, a multi-institutional, randomized controlled 179

trial to evaluate a novel cultural dexterity curriculum in surgical residencies across the United States. D. NEIL AND ELISE WALLACE STRATUS CENTER FOR MEDICAL SIMULATION The Neil and Elise Wallace STRATUS Center for Medical Simulation at Brigham and Women’s Hospital opened in February 2004. Initially encompassing 1,500 square feet of space, its primary focus was on team training and emergency management. Developed by the Department of Emergency Medicine, the Harvard Affiliated Emergency Medicine Residency integrated its curriculum into the simulation center, limiting lecture-based education to grand rounds and medical management conference. Other departments were invited to use this new facility and STRATUS quickly became part of the lexicon of the institution. In 2007, and in large part due to the needs of the Department of Surgery, Brigham and Women’s Hospital recognized medical simulation as a necessary component of modern graduate medical education. After organizing a multidisciplinary team of medical educators, STRATUS expanded to its current state, with more than 6,000 square feet of space that includes: two human patient simulation suites, a 500 square foot operating room/delivery suite, a virtual reality endoscopic/laparoscopic simulation arcade, a part task laboratory, a microsimulation laboratory as well as conference and classroom facilities. The DOS has been a major user of STRATUS since 2007. The general surgery residency curriculum includes an intern boot camp as well as a longitudinal curriculum throughout the residency. This curriculum encompasses technical skills in both open and laparoscopic surgery and non-technical skills such as leadership and communication. A number of divisions within the department utilize STRATUS as well, including the Division of Thoracic and Cardiac Surgery with its fellow boot camp, and many others making use of the robotic simulator to train and credential their surgeons and trainees. Faculty within the department have also benefitted 180

from STRATUS, as the DOS participates in the OR Team Training with Simulation Program, which teaches teamwork and communication to full OR teams, focused on attending surgeons, anesthesiologists, and nurses. E. MEDICAL STUDENT TEACHING The Department of Surgery offers a 12-week Core Surgery Clerkship to familiarize Harvard Medical School students with diseases encountered by surgeons, and to gain insight into surgical decision- making. Primary Core Clerkship in Surgery The 12-week surgery clerkship includes two three-week inpatient rotations. During these rotations, the student participates in the daily activities of an inpatient general surgery service and sees outpatients with two general surgery preceptors. In addition, the student participates in two two-week elective rotations in surgical subspecialty services. Students are also required to complete a one-week rotation in anesthesiology and a one-week rotation in the breast service. For five of the 12 weeks, the students spend one 12-hour shift each weekend in the Emergency Department overseeing surgical consults. Reza Askari, MD, has been the director of the Brigham Core Surgery Clerkship since 2017. Throughout his tenure as clerkship director, Dr. Askari has continually reassessed and reorganized aspects of the surgery clerkship to enhance the learning experience of third-year Harvard medical students. Over the past several years, Dr. Askari has introduced several educational tools and innovations to increase the effectiveness of the teaching program: 1. Expanded the topics covered during the Wednesday didactic conferences (e.g., non-technical skills, wellness, and global health). 2. Incorporated a Mini-Clinical Evaluation Exercise (Mini-CEX) in addition to oral exams. 3. Increased independent study time throughout the clerkship in advance of final exams. 4. Introduced three half-day \"wellness days\" for students during each 12-week block. Students are excused from all clinical duties during this time. 5. Continued and revamped simulation education during the clerkship. Surgery Electives Each year (pre-COVID), the department welcomes approximately 75 elective students for one-month electives in the specialties of cardiac surgery, otolaryngology, plastic surgery, surgical critical care, thoracic surgery and urology. There is also a general surgery course that accepts up to six students per month, with a choice of acute care surgery, breast surgery, colorectal surgery, general/gastrointestinal surgery, surgical oncology and vascular surgery. 181

Mark Fairweather, MD, was hired into an official role as the course director of advanced elective students in June 2021. He oversees all the organization, grading and education of these students. Dr. Fairweather meets with each student for one-on-one mentorship at the beginning and at the conclusion of their rotation. Additionally, the education office is currently developing an advanced elective student curriculum, which will feature a weekly student conference led by surgery residents, as well as a monthly meet-and-greet dinner with students and residents. OT501M.23 Advanced Clinical Otolaryngology - Head and Neck Surgery Director: Rachel Roditi, MD Description: This course provides in-depth exposure to the field of otolaryngology/head and neck surgery and its principal subspecialty areas including otology, neuro-otology, and head and neck surgical oncology. A combination of clinical opportunities in inpatient and ambulatory ORL-HNS subspecialties and related fields are tailored to the career objectives of the student. The student will be an active participant on the inpatient service, making rounds and providing care under supervision. Students participate in the operating room and follow those patients postoperatively. Students will perform consultations in the outpatient clinic setting with attending physicians, who will provide feedback about the student’s performance. Attendance at daily rounds, clinics and selected operations is expected. SU501M.23 General Surgery Director: Mark Fairweather, MD Description: This course will give students an in-depth experience in clinical management of patients with surgical problems on one of the six general surgery services at Brigham and Women’s Hospital: surgical oncology/breast, surgical oncology/endocrine, colorectal, GI/minimally invasive, vascular and emergency general surgery/trauma. Students will serve as clerks on a busy general surgical service and are expected to perform close to the level of an intern. The course will provide the opportunity to gain experience in preoperative, intraoperative and postoperative patient management, including evaluating patients, deciding on a diagnostic and management strategy, and providing care under supervision. The student will do up to four overnight/weekend shifts during the rotation, after discussion with the preceptor. The elective student will assist in management of patients in clinic and on the floor and will participate actively in procedures in the operating room. SU504M.23 Clinical and Experimental Cardiac Surgery Director: Ashraf Sabe, MD Description: The course is designed to acquaint students with the concepts, philosophy and techniques of clinical cardiac surgery. There will be opportunities to participate in pre- and postoperative care of cardiac surgical patients and assist at cardiac operations at the Brigham. Weekly lectures in clinical cardiology, conferences on preoperative evaluation of cardiac surgical patients, and rounds in the 182

intensive care units and general wards will be conducted. The course will give students sufficient experience in an academic atmosphere to judge the depth of their own interest in cardiac surgery. SU514M.Ja Plastic and Reconstructive Surgery Director: Justin Broyles, MD Description: The advanced plastic surgery elective exposes students to a wide array of reconstructive and cosmetic surgical patients seen in the practices of the 10 attending surgeons at Brigham and Women's Hospital. Areas of focus include head and neck trauma, hand surgery and cosmetic surgery, as well as reconstruction of the head and neck, breast, trunk, genitourinary system and the lower extremity. Students will function as sub-interns, assisting the Harvard Plastic Surgery residents with patient rounds, inpatient evaluation and operative procedures. In addition, students will be exposed to surgical management of wounds and pre- and postoperative care in the outpatient clinic. Students will participate in Grand Rounds and teaching conferences and will be expected to do a brief presentation at the end of their rotation. SU518M.23a Diseases of the Genitourinary Tract Director: Martin Kathrins, MD Description: This course is designed to enable students to concentrate on the clinical aspects of adult and pediatric urologic surgery, including pathology, physiology and radiology. Students will participate as members of the patient care team in diagnosis, clinical management and surgical treatment of patients with urologic disorders. Each student will review pertinent medical literature using evidence- based medicine and present to group conferences on special categories of interest in urologic surgery, such as renal calculi or neoplastic diseases of the genitourinary system. SU518M.23b Urologic Oncology Director: Martin Kathrins, MD Description: The increasing emphasis on a multidisciplinary approach to the treatment of genitourinary neoplasms has dramatically improved survival rates. This rotation acquaints students with the rapidly changing field of genitourinary oncology, providing a broad basic background for development of a systematic approach to many different tumor systems. The curriculum includes longitudinal exposure to patients with various malignancies; intraoperative exposure to open and minimally invasive urologic surgical procedures; correlation of histopathology with the patient's clinical course; understanding decision-making, including chemotherapy, radiotherapy and immunotherapy; and in-depth seminars covering various urologic malignancies. 183

SU518M.J Adult and Pediatric Urology Director: Michael Kurtz, MD, Boston Children’s Hospital Description: This course gives students broad exposure to reconstructive techniques and urologic disease in adults and children. For three weeks, students will rotate on the urology service at Brigham and Women's Hospital, and for one week, students will rotate at Boston Children's Hospital. Students will have access to robotic, laparoscopic and abdominal ultrasound simulators in a dedicated simulation lab. The experience includes opportunities for rotation in the operating room, general and oncology clinics, multidisciplinary specialty clinics and urodynamics. Special emphasis is given to genitourinary reconstruction for acquired and congenital disease. A 20-minute presentation on a urologic topic of the student's choice is to be given at the end of the rotation to trainees and faculty. SU526M.23 General Thoracic Surgery Director: Ciaran McNamee, MD Description: PGY-4 students serve as sub-interns on one of the busiest thoracic surgery services in the United States. Operations range from open extrapleural pneumonectomies to minimally invasive esophageal and lung resections, to airway and esophageal stents. Starting with responsibility for two patients, students increase their clinical load as comprehension and confidence increases. Students will develop knowledge of clinical tests of cardiorespiratory reserve and become comfortable with postoperative management of non-cardiac thoracic surgery patients. Students are supported by didactic conferences, including multidisciplinary conferences, with the participation of radiology, pathology, medical oncology and thoracic surgery faculty. Students have the opportunity to participate in an actively growing lung transplant program. They will make clinical rounds on the thoracic surgical service on a daily basis and are expected to increase their knowledge and skill up to the capacity of an intern for their assigned patients. This is an operative rotation, and participation in the OR is an integral part of the experience. This includes teaching of basic surgical skills and encouragement of technical excellence. Students will become facile with bronchoscopy and endoscopy. This course is specifically designed to increase the confidence and skill of well-prepared PGY-4 students as they move toward surgical internship. SU535M.23 Surgical Critical Care Trauma and Burn Management Director: Stephanie Nitzschke, MD, MS Description: This course has a didactic and a clinical component. The didactic component consists of daily morning lectures, teaching rounds in the SICU and in the burn and trauma ICU and x-ray rounds. The ICU service provides daily conferences on all aspects of critical care. There is a weekly critical care fellow's presentation, a trauma conference and a thoracic surgery ICU conference. There is also a weekly ICU/infectious disease conference. The clinical experience component focuses on all aspects of critical 184

care, including ventilation management and nutritional support, as well as management of the severely traumatized and burned patients. The student is expected to learn the basic physiologic, metabolic and immunologic abnormalities which occur in critical illness, including the basic approaches to diagnosis and management of surgical critical care patients. This sub-internship provides an excellent opportunity for students to enhance their knowledge of postoperative management of complex patients following trauma or postoperative physiological derangements. Additional Harvard Medical School Teaching by Department Faculty Exhibit 22: HMS Teaching by DOS Faculty (2017 – 2021) ACADEMIC HARVARD MEDICAL SCHOOL EDUCATION YEAR Faculty Member Course Title Role AY17 Reza Askari Transition to the PCE-BWH PCE and Selectives Site Allocations AY18 Longitudinal Conference Preceptors Elizabeth Breen PCE-BWH Procedural Skills Tutorial Giorgio Giatsidis Assistant Director Joaquim Havens PCE-BWH PCE and Selectives Site Allocations Jennifer Irani Transition to the PCE-BWH Lab Instructor-Anatomy Chandrajit Raut Transition to the PCE Lab Instructor Douglas Smink Foundations PD3 Faculty PCE-BWH Lecturer Edward Whang Co-Director Introduction to Clinical Medicine Advisor Reza Askari PCE and Selectives Site Allocations Matthew Giangola PCE-BWH Surgical Patient Procurers Giorgio Giatsidis Transition to the PCE-BWH Surgical Preceptors/BWH DOS Joaquim Havens Introduction to Clinical Medicine Jennifer Irani Introduction to Clinical Medicine Core Clerkship-Teaching and Assessment Edward Kwasnik Surgery Clerkship Core Clerkship-Director Surgery Clerkship-Overlap Core Clerkship-Administrator Surgery Clerkship-Overlap Surgery Clerkship-Overlap Core Clerkship-Teaching and Assessment Homeostasis II Collaborative Learning Faculty Transition to the PCE-BWH PCE and Advanced Clinical Imm Transition to the PCE-BWH PCE and Advanced Clinical Imm Immunity in Defense and Disease Lab Instructor Foundations Lab Instructor Transition to the PCE Lab Instructor PCE-BWH PD3 Faculty Introduction to Clinical Medicine Lecturer Co-Director Immunity in Defense and Disease Lab Instructor Homeostasis II Collaborative Learning Faculty 185

Chandrajit Raut Foundations Lab Instructor Jeffrey Skubic Transition to the PCE Lab Instructor Edward Whang PCE-BWH Advisor Reza Askari PCE-BWH Advisor Joaquim Havens Transition to the PCE-BWH PCE and Advanced Clinical Imme Jennifer Irani Introduction to Clinical Medicine Surgical Preceptors/BWH DOS Surgery Clerkship Core Clerkship-Teaching and Assessment Edward Kwasnik Practice of Medicine-MGH Clinical Experience Faina Nakhlis Ambulatory-Central Malcolm Robinson Eric Sheu Homeostasis II Case-Based Collaborative Scott Shikora AY19 Ali Tavakkoli PCE-BWH PD3 Faculty AY20 Ashley Vernon Introduction to Clinical Medicine Lecturer Co-Director Joaquim Havens Professional Development Week I OSCE Exam Trainer Jennifer Irani PCE OSCE Exam Trainer Immunity in Defense and Disease Lab Instructor Edward Kwasnik Capstone OSCE Exam Trainer Homeostasis I Collaborative Learning Faculty Homeostasis II Case-Based Collaborative Foundations Lab Instructor Transition to the PCE Lab Instructor PCE-BWH Advisor Preceptor AISC-Metabolism, Nutrition and Lifestyle Medicine Preceptor AISC-Metabolism, Nutrition and Lifestyle Medicine Preceptor AISC-Metabolism, Nutrition and Lifestyle Medicine Preceptor AISC-Metabolism, Nutrition and Lifestyle Medicine AISC-Metabolism, Nutrition and Lifestyle Medicine Preceptor Introduction to Clinical Medicine Surgery Clerkship Surgical Preceptors/BWH DOS Core Clerkship-Teaching and Asse Capstone Clinical Sessions-Surgery PCE-BWH PD3 Faculty Introduction to Clinical Medicine Lecturer Co-Director Immunity in Defense and Disease Lab Instructor Homeostasis I Collaborative Learning Faculty Foundations Lab Instructor Transition To PCE Lab Instructor 186

Faina Nakhlis PCE-BWH Advisor Jamie Robertson Essentials of the Profession II Small Group Leader Essentials of the Profession Team-Building Malcolm Robinson Small Group Session Leader Scott Swanson Large Group Leader Joaquim Havens Small Group Leader Jennifer Irani AY21 AISC-Metabolism, Nutrition and Lifestyle Medicine Lecturer Edward Kwasnik Introduction to Clinical Medicine Capstone Surgical Preceptors/BWH DOS Faina Nakhlis Surgery Clerkship Clinical Sessions-Surgery Daniel Rinewalt PCE-BWH Core Clerkship-Teaching and Assessment Jamie Robertson Principal Clinical Experience-BWH PD3 Faculty Scott Swanson PD3 Faculty Introduction to Clinical Medicine Lecturer Co-Director PCE-Advanced Clinical Content and Skills Weeks Small Group Session Leader Homeostasis I Lab Instructor Homeostasis II Lab Instructor Foundations Collaborative Learning Faculty PCE-BWH Principal Clinical Experience-BWH Advisor-Head Homeostasis I Advisor-Head Foundations Lab Instructor Essentials of the Profession II Collaborative Learning Faculty Introduction to Clinical Medicine Lecturer Qualifying Sub-I Clerkship Clinical Capstone Surgical Preceptors/BWH DOS Surgery Clerkship Surgery Clinical Sessions-Surgery Core Clerkship-Teaching and Assessment 187

F. CURRENT RESIDENCY PROGRAMS The department offers six residency programs, which are listed below. In addition, refer to Appendix 2 for a detailed description of each program. Brigham-Based Name Length Number of Program Director Residents General Surgery 5 years +/- Stephanie Nitzschke, MD, Cardiothoracic Surgery Integrated (I-6) 2 years 9 categorical MS Program research per year Urology 6 years 2 per year Michael Jaklitsch, MD 5 years 3 categorical George Haleblian, MD per year Oral Medicine 3 years 2 per year Piamkamon Vacharotayangul, DDS, PhD Combined Programs Name Length Number of Program Director Mass Eye and Ear (MEE) Otolaryngology 5 years Residents Stacey Gray, MD 5 per year Harvard Plastic Surgery 6 years 3 integrated Kyle Eberlin, MD per year 3 years 2 independent per year 188

G. CURRENT FELLOWSHIP PROGRAMS The department offers 16 fellowship programs, which are listed below. In addition, refer to Appendix 3 for a detailed description of each program. Name Length Number of Program Director Fellows Acute Care Surgery Fellowship 1 year Reza Askari, MD Adult Cardiac Surgery Fellowship 1 year 1-2 per year Tsuyoshi Kaneko, MD Advanced Laparoscopic Fellowship 1 year 1 per year Ali Tavakkoli, MD Breast Surgery Fellowship 2 years 1 per year Tari King, MD Cardiothoracic Surgery Fellowship 2 years 2 per year Michael Jaklitsch, MD Cardiothoracic Surgery Transplant 4 per year Fellowship 1 year 1 per year Antonio Coppolino, MD Colorectal Surgery Fellowship Nelya Melnitchouk, MD, Endocrine Surgery Fellowship 1 year 1 per year MSc Endovascular Cardiac Surgery Fellowship 1 year 1 per year Matthew Nehs, MD General Thoracic Surgery Fellowship 1 year 1 per year Tsuyoshi Kaneko, MD Minimally Invasive Thoracic Surgery 1 year 1 per year Michael Jaklitsch, MD Fellowship Surgical Critical Care Fellowship 1 year 1 per year Jon Wee, MD Surgical Clinical Nutrition Support 1 year 4 per year Reza Askari, MD Fellowship Complex Surgical Oncology Fellowship 1 year 1 per year Malcolm Robinson, MD Urological Oncology Fellowship 2 years 1 per year Mark Fairweather, MD Vascular Surgery Fellowship 2 years 2 per year Steven Chang, MD, MS 2 years 2 per year Matthew Menard, MD H. CONTINUING MEDICAL EDUCATION Along with various specialty conferences within each of the surgical divisions, there are two weekly department-wide CME category 1 accredited teaching conferences. • The Morbidity and Mortality (M&M) conference is geared toward quality improvement, with three patient complications discussed each week. Each case is presented by a resident or fellow, with the attending surgeon participating, and is moderated by the CME course director. Discussion focuses on the technical and non-technical contributors to the complication, including the contribution of social determinates, but also on quality improvement that could minimize the risk of the complication in the future. Edward Whang, MD, is the course director for the M&M conferences, which has an average attendance of 85 people. 189

• Surgical Grand Rounds Conferences feature Harvard faculty members, as well as distinguished speakers from other institutions, covering a variety of basic science, clinical science, diversity and equity, and ethically related topics of interest, fulfilling ACGME core competencies and JCHAO requirements for residents, faculty and staff. CME for these conferences is granted through the Mass General Brigham Office of Continuing Professional Development. C. Keith Ozaki, MD, is the Grand Rounds course director. The conferences receive an average attendance of 70 people. Grand Rounds are designed to review diverse subjects to stimulate learning and discussion, direct future research and enhance collaborations. The curriculum is designed over a three to four-year cycle to address all practice areas in which such a gap might exist. The gaps address the latest methods of treatment, the results of the latest treatment or the latest understanding of disease pathogenesis across the entire range of surgery. This forum also addresses gaps in knowledge related to principles of health care utilization, ethical consideration, end-of-life issues, as well as risk management policies. Another major CME-accredited conference includes the Updates in General & GI Surgery, organized by the Division of General and Gastrointestinal Surgery. This three-day course is divided into three half- days with sessions focused on general surgery, colorectal surgery and bariatric surgery, including hernia management. Each module within those sessions includes a lecture, case presentation, panel discussion and Q&A session. Participants can discuss management of common GI surgical problems and weigh the pros and cons of the different treatment strategies. Participants also discuss management of abdominal wall and hiatal hernias, common colorectal conditions (e.g., anorectal disease, diverticular disease and colon cancer), biliary disease and complications, and surgical approaches to weight management. Overall, learners are equipped with new perspectives, treatment options and patient care methods, which they can bring back to their home institutions. Ali Tavakkoli, MD, is the course director for this program, which was introduced in September 2021 with 51 total attendees from across the globe. To support ongoing CME participation outside of department offerings including attendance at national meetings, the department provides $6,000 per year to each faculty member to be used at their discretion. To further incentivize participation in teaching and education, faculty members can earn an additional $1,000 per quarter (up to $10,000 annually in total) by participating in various education activities, such as interviewing resident or fellowship applicants, or teaching in the simulation laboratory. Other divisional CME-accredited conferences include: • Office of Professional Development Professional Fulfillment Series • Cardiothoracic Grand Rounds • Transplant Monthly Quality Assessment and Performance Improvement (QAPI) • Urology Grand Rounds • Urology Tumor Boards • Advanced Trauma Life Support (ATLS) Course 190

• Plastics Grand Rounds (in combination with MGH) • Esophageal Course • Lung Nodule Course • Chest Wall Course • Levin Lung Cancer Symposium • Cardiothoracic Surgery M&M • Lung Cancer Tumor Board • Esophageal Cancer Tumor Board • Stepping Strong Trauma Research and Innovation Symposium • Stepping Strong Injury Prevention Program Lunch & Learns I. VISITING PROFESSORS In addition to the regular Grand Rounds scheduling structure, the Department of Surgery hosts nine named visiting professors, as well as 11 named visiting professors sponsored by the divisions. A full list of named visiting professors can be found below, as well as the surgery education visiting professors. A few notable visiting professors include: • Mary Hawn – Stanford University • Tomislav Mihaljevic – Cleveland Clinic • Joanna Chikwe – Cedars-Sinai • Steven Rosenberg – National Cancer Institite • Gail Darling – University of Toronto • Nancy Ascher – UC San Francisco Exhibit 23: Visiting Professor Lecture Series Academic Year Lecturer Francis D. Moore Pro Tempore Visiting Professor in Surgery Institution 2015-2016 Jeffrey B. Matthews, MD University of Chicago Medicine ​ 2016-2017 John A. Olson, MD, PhD Presentation Title University of Maryland School of Medicine​ 2017-2018 Mary T. Hawn, MD, MPH, FACS Truth and Truthiness in Surgery Stanford University School of Medicine Timothy M. Pawlik, MD, MPH, The (Not-so) Trivial Pursuit of Primary Hyperparathyroidism: \"So who was Isaac Olch?\" 2018-2019 MTS, PhD, FACS, FRACS Big Data: Promises and Pitfalls Ohio State University College of Medicine Cure, Communication and Confusion: Aligning Goals of Cure for Our Cancer Patients Academic Year Lecturer Gordon C. Vineyard Lecturer in Surgery Institution Boston University School of Medicine 2016-2017 David McAnenay, MD Presentation Title University of Michigan School of Medicine A Heritage of Excellence Geisel School of Medicine at Dartmouth 2017-2018 Robert H. Bartlett, MD Surgical Research MITRE Health Leadership Lessons from Clinical Advances in Melanoma 2018-2019 Sandra L. Wong, MD, MS TBD 2021-2022 Jay J. Schnitzer, MD, PhD 191

Lawrence and Judith Schlager Family Lecturer in Surgical Oncology Academic Year Lecturer Presentation Title Institution 2016-2017 Raphael E. Pollock, MD, PhD Soft Tissue Tumors: Opportunities for Investigation and Collaboration Ohio State University​ 2017-2018 Andy Lowy, MD, FACS Novel Targets of the Pancreatic Cancer Chimera University of California, San Diego​ 2018-2019 Jeffrey A. Drebin, MD, PhD Translational Cancer Research: A Surgeon's Tale Memorial Sloan Kettering Cancer Center 2019-2020 Jennifer Tseng, MD, MPH Moving from Disparities to Cancer Treatment Equity: The View from Boston Medical Center Boston Medical Center 2021-2022 Carol Swallow MD, FRCSC Impossible is Nothing? The Power and Pain of International Collaboration to Improve Surgical University of Toronto Care for Rare Conditions Academic Year Lecturer Hechtman Trauma Lecturer in Surgery Institution 2016-2017 Raul Coimbra, MD, PhD University of California, San Diego​ 2017-2018 Eileen Bulger, MD Presentation Title University of Washington 2018-2019 Hasan B. Alam, MD The Brain-Gut-Lung Axis: Uncovering Multiple Organ Failure after Trauma University of Michigan Medical School 2020-2021 David A. Spain, MD Optimizing Prehospital Trauma Care through Research Stanford University School of Medicine Academic Life as a Trauma Surgeon: Lessons Learned After the Trauma Nina S. Braunwald Lecturer in Surgery Academic Year Lecturer Presentation Title Institution 2015-2016 2016-2017 Rosemary F. Kelly, MD Resilience: How our Hearts Recover University of Minnesota 2017-2018 2018-2019 Yolonda L. Colson, MD, PhD Oh, the Places You Will Go! Brigham and Women’s Hospital 2019-2020 Joanna Chikwe, MD Resilience Stony Brook Medicine Caprice C. Greenberg, MD, MPH Stop Fixing Women University of Wisconsin School of Medicine and Public Health Jennifer Romano, MD, MS, FACS, FACC Family Planning and the Surgical Trainee: Changing University of Michigan Medical School ​ Landscape and Awareness Gelman-Zinner Visiting Professor in Surgery, Anesthesiology, Perioperative and Pain Medicine Academic Year Lecturer Presentation Title Institution 2016-2017 Peter J. Pronovost, MD, PhD Toward Eliminating All Harms Johns Hopkins University School of Medicine 2017-2018 Taylor S. Riall, MD, PhD, FACS Maintaining the Fire: Physician Wellbeing, Resilience and Intentional Culture Arizona Cancer Center 2018-2019 Tomislav Mihaljevic, MD 2021-2022 Michael W. Mulholland, MD, PhD Cleveland Clinic 5-Year Strategy/Tiered Daily Huddles Cleveland Clinic Lerner College of Medicine of Case Western Reserve University TBD University of Michigan Medical School Academic Year Lecturer Dorothy R. Eisenberg Lecturer in Surgery Institution 2015-2016 Anthony Atala, MD Presentation Title Wake Forest School of Medicine George Washington University School of 2017-2018 Kurt Newman, MD Surgeon to CEO: Ten Lessons from a 30-Year Career Medicine and Public Health TBD University of Chicago Medicine 2021-2022 John C. Alverdy, MD, FACS Academic Year Lecturer Lawrence H. Cohn Visiting Professor in Cardiac Surgery Institution 2016-2017 David P. Taggart, MD (Hons), PhD Presentation Title University of Oxford​ 2017-2018 2018-2019  A.P. Kappetein, MD, PhD Using Randomized Trials to Distort Clinical Practice Erasmus University Medical Center, Rotterdam, Netherlands 2019-2020 2020-2021 Gebrine El Khoury, MD Maximizing Knowledge from Clinical Trial Data; Changing Face of Cliniques Universitaires Saint-Luc Brussels, Belgium 2021-2022 Scientific Research in Cardiac Surgery Cleveland Clinic Lerner College of Medicine of Case Western A. Marc Gillinov, MD Aortic Valve Repair: State of the Art Reserve University Washington University School of Medicine in St. Louis ​ Ralph J. Damiano, Jr., MD Robotic Mitral Valve Surgery: State of the Art Stanford University School of Medicine Joseph Woo, MD The Evolving Surgical Treatment of Lone Atrial Fibrillation TBD 192

Richard E. Wilson Visiting Professor in Surgical Oncology Academic Year Lecturer Presentation Title Institution 2017-2018 George Washington University School of Steven Rosenberg, MD, PhD Lymphocytes as a Drug for the Treatment of Cancer Medicine and Health Sciences 2018-2019 Perelman School of Medicine at the 2020-2021 Ronald DeMatteo, MD Interaction of Tyrosine Kinase Inhibition and Immunity in GIST University of Pennsylvania Nita Ahuja, MD, MBA Nature vs. Nurture: Epigenetics and Leadership in Academia Yale School of Medicine David J. Sugarbaker Lecturer in Thoracic Surgery Academic Year Lecturer Presentation Title Institution 2016-2017 2017-2018 Bryan Myers, MD, MPH Stage 1 Lung Cancer, Treatment Options, Barriers to Objective Decision- Washington University 2018-2019 Making on Therapy 2019-2020 Duke University Thomas D’Amico, MD Thoracoscopic Lobectomy: Past, Present, Future Medical University of Vienna, Austria 2021-2022 Walter Klepetko, MD ECLS in Lung Transplantation and General Thoracic Surgery University of Toronto Gail E. Darling, MD, FRCSC, FACS Innovations in Surgery: Improving Patient Outcomes After Seoul National University College of Esophagectomy Medicine Young Tae Kim, MD, PhD A Surgeon’s Journey in the Translational Research of Lung Cancer Gerald and Elaine Schuster Distinguished Lecturer in Thoracic Surgery Academic Year Lecturer Presentation Title Institution 2016-2017 St. John’s Health Center 2017-2018 Robert McKenna, Jr., MD Fast Tracking and Cost Effectiveness for VATS Lobectomy Mayo Clinic College of Medicine & Science 2018-2019 MD Anderson Cancer Center Mark Allen, MD E-Learning for Thoracic Surgery 2020-2021 Fudan University Shanghai Cancer Center  Ara Vaporciyan, MD, FACS, MHPE Modernizing Pedagogy in Cardiothoracic Surgical Education Haiquan Chen, MD Individualized Surgical Treatment Strategy for Early-Stage Lung Cancer: Translation of Knowledge Joseph E. Murray Visiting Professor in Plastic Surgery Academic Year Lecturer Presentation Title Institution Regenerative Peripheral Nerve Interfaces for Control of 2016-2017 Paul S. Cederna, MD Neuroprosthetic Devices University of Michigan School of Medicine Suturable Mesh: A New Concept for Load Bearing Closures 2018-2019 Greg Dumanian, MD Loss of Hypoxia Signaling Impairs Muscle Function in Aging Northwestern University 2020-2021 Indranil Sinha, MD TBD Brigham and Women’s Hospital 2021-2022 Justin M. Sacks, MD, MBA, FACS Washington University in St. Louis Joseph E. Murray Visiting Professor in Transplant Surgery Academic Year Lecturer Presentation Title Institution 2016-2017 A. Joseph Tector, III, MD, PhD Xenotransplantation: A Clinical Reality? University of Alabama at Birmingham School of Medicine​ 2017-2018 Peter Friend, MD Pancreas Transplantation: State-of-the-Art University of Minnesota School of Medicine 2018-2019 Nancy L. Ascher, MD, PhD Surgical Innovation in the 21st Century UCSF School of Medicine 2019-2020 Donna L. Farber, PhD Why Does Surgery Need Basic Research? Columbia University Medical Center John A. Mannick Visiting Professor in Vascular Surgery Academic Year Lecturer Presentation Title Institution 2016-2017 Bruce A. Perler, MD, MBA Evidence-Based Medicine and the Contemporary Management of Johns Hopkins University School of Medicine Carotid Artery Disease: After 60 Years, the Controversies Continue 2017-2018 Andres Schanzer, MD The Evolving Treatment of Aortic Disease: The Future is Now University of Massachusetts Medical School 2018-2019 Ronald M. Fairman, MD 20 + Years of Aortic Clinical Trials for Aneurysmal Disease Perelman School of Medicine at the University of Pennsylvania  193

Visiting Professor in Professional Development Academic Year Lecturer Presentation Title Institution University of Utah School of Medicine 2019-2020 Thomas K. Varghese Jr., Reflections on Diversity and Inclusion: Mentorship, Cochrane Library Brigham and Women's Hospital MD, MS, FACS Sponsorship and Equity 2020-2021 Karla Soares-Weiser, MD, Leadership, Systematic Reviews and COVID: An International PhD, MSc Perspective 2021-2022 Imoigele P. Aisiku, MD, Leadership: A Financial Perspective MBA Chief Resident Visiting Professor Academic Year Lecturer Presentation Title Institution 2017-2018 Johns Hopkins 2018-2019 Dorry Segev, MD, PhD Big Data: What's the Big Deal? University of Chicago 2019-2020 Selwyn O. Rogers, Jr., MD, MPH Violence Seen Through a Public Health Lens Northwestern School of Medicine 2020-2021 Karl Bilimoria, MD, MS Fanning the Burnout Fire: How our Misconceptions and Good Royal College of Surgeons of England 2021-2022 Intentions Could Fail Tomorrow’s Surgeons Medical University of South Carolina David Nott, MD, FRCS, DSc, OBE Leaving a Legacy in a Warzone David Mahvi, MD Finding your Path to a Surgical Career Visiting Professor in Surgery Education Academic Year Lecturer Presentation Title Institution University of Wisconsin 2016-2017 Rebecca Minter, MD The Promise of EPAs – A Paradigm Shift for Washington University in St. Louis Competency-Based Surgical Training? University of Toronto 2017-2018 Mary Klingensmith, MD Competency-Based Education in Surgery Brigham and Women's Hospital 2018-2019 Teodor Grantcharov, MD, PhD, FRCSC Using Data to Improve Education, Performance and Harvard University Surgical Safety American Board of Surgery 2019-2020 Nora Osman, MD Widening the Field: Mitigating Bias in the Learning Environment 2020-2021 Gary P. Cormier, MA Self-Management and Communication During High Stress Situations: A Personality-Based Approach 2021-2022 Jo Buyske, MD, DABS Pending J. CONSTRAINTS AND CHALLENGES Like most surgical training programs, we grapple with many of the same challenges in surgical education. Diversity is an important goal for us, and we are successful at attracting a diverse group of trainees. With that said, we strive for an even more diverse and inclusive group of trainees and faculty, and we have some challenges in providing mentorship to our diverse trainees. We are also focused on the learning environment for students, residents and fellows. As surgical care has become increasingly complex, we need to remember to create time for constructive feedback, direct teaching and faculty development — activities that we now incentivize for both faculty and department leaders. Feedback from our student and resident surveys (see Appendix 4) shows that we need to improve the learning environment, particularly around how we interact with both trainees and our colleagues around the hospital. We have initiated a number of projects directly focused on these issues. Finally, we constantly work to create the right balance of trainee autonomy, while providing the safest, highest quality care possible. 194

Work Hours Compliance In January 2020, the General Surgery Residency was placed on accreditation with warning from the ACGME, which included a citation for work hours. We have subsequently been moved to continued accreditation status. Department leaders continue to vigorously communicate the expectation that residents should be in complete compliance with work hours regulations as mandated by the ACGME. This importance of compliance has been communicated with the residents, faculty and department chair. Success requires diligence and compliance with all members involved with the residency. All interventions from the prior two years remain in place and we have implemented the following strategies to ensure compliance: 1. Work hour violations are reviewed at the weekly program director meeting. The issues surrounding each violation are discussed with the residents so that appropriate interventions can be made. 2. The Chief residents of each service are empowered to send residents home if they are in jeopardy of hours violations. This strategy has been particularly effective and it is utilized regularly. This process has improved over the past year as senior residents have become more engagement in this initiative. 3. In order to facilitate timely sign in and sign outs we have asked for increased PA coverage on our busy surgical services. Thus far we have been approved for two PAs on the General Surgery Service and have requested one PA for the Vascular and Endovascular Surgery Service. 4. The program director has met with the residents, both as a collective and with individual classes, to request complete transparency around work hours. As a result, residents have communicated issues, in real time, where hours violations were imminent and we have been able to make changes to schedules so that violations do not occur. This strategy has improved over time and is more effective with each new year. 195

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