A Multi-Modal Approach to Islet and Pancreas Transplantation With Calcineurin-Sparing Immunosuppression Maintains Long-Term Insulin Independence in Patients With Type I Diabetes.

Long-term success in beta-cell replacement remains limited by the toxic effects of calcineurin inhibitors (CNI) on beta-cells and renal function. We report a multi-modal approach including islet and pancreas-after-islet (PAI) transplant utilizing calcineurin-sparing immunosuppression. Ten consecutive non-uremic patients with Type 1 diabetes underwent islet transplant with immunosuppression based on belatacept (BELA; n = 5) or efalizumab (EFA; n = 5). Following islet failure, patients were considered for repeat islet infusion and/or PAI transplant. 70% of patients (four EFA, three BELA) maintained insulin independence at 10 years post-islet transplant, including four patients receiving a single islet infusion and three patients undergoing PAI transplant. 60% remain insulin independent at mean follow-up of 13.3 ± 1.1 years, including one patient 9 years after discontinuing all immunosuppression for adverse events, suggesting operational tolerance. All patients who underwent repeat islet transplant experienced graft failure. Overall, patients demonstrated preserved renal function, with a mild decrease in GFR from 76.5 ± 23.1 mL/min to 50.2 ± 27.1 mL/min (p = 0.192). Patients undergoing PAI showed the greatest degree of renal impairment following initiation of CNI (56% ± 18.7% decrease in GFR). In our series, repeat islet transplant is ineffective at maintaining long-term insulin independence. PAI results in durable insulin independence but is associated with impaired renal function secondary to CNI dependence.

The incidence and natural history of ascites after liver transplantation.

BACKGROUND: Ascites is common in cirrhosis but uncommon after liver transplant. We aimed to characterize the incidence, natural history, and current management strategies of post-transplant ascites. METHODS: We performed a retrospective cohort study of patients who underwent liver transplantation at 2 centers. We included patients who underwent deceased donor whole graft liver transplants between 2002 and 2019. Chart review identified patients with post-transplant ascites, requiring a paracentesis between 1 and 6-month post-transplants. Detailed chart review identified clinical and transplant characteristics, evaluation of ascites etiology, and treatments. RESULTS: Of 1591 patients who successfully underwent a first-time orthotopic liver transplant for chronic liver disease, 101 (6.3%) developed post-transplant ascites. Only 62% of these patients required large volume paracentesis for ascites before transplant. 36% of patients with post-transplant ascites had early allograft dysfunction. Most patients with post-transplant ascites (73%) required a paracentesis within 2 months of transplant, but 27% had delayed ascites onset. From 2002 to 2019, ascites studies were obtained less often, and hepatic vein pressure measurement was performed more often. Diuretics were the mainstay of treatment (58%). The use of albumin infusion and splenic artery embolization to treat post-transplant ascites increased over time. Larger pre-transplant spleen size was associated with a greater number of post-transplant paracenteses (r=0.32 and p=0.003). For patients who underwent splenic intervention, paracentesis frequency was significantly reduced (1.6-0.4 paracenteses/month, p=0.0001). The majority (72%) of patients had clinical resolution of their ascites at 6-month post-transplant. CONCLUSIONS: Persistent or recurrent ascites continues to be a clinical issue in the modern era of liver transplantation. Most had clinical resolution within 6 months, some requiring intervention.

Distributions of Residency Interviews With the Implementation of Virtual Interviews and Standardization of Interview Offer Dates.

OBJECTIVE: Virtual interviews were widely implemented alongside many other changes in the 2021 residency application process. We investigated how these many interventions may have influenced interview distributions and completions. DESIGN: Cross-sectional survey distributed electronically to obstetrics and gynecology (OBGYN) residency applicants in February 2021. Distributions of interview invitations, interviews completed, and percent of interview offers completed were compared to the previous application cycle. The odds ratios of receiving interviews were calculated based on applicant characteristics including test scores, number of applications, and race/ethnicity. SETTING: All OBGYN residency applicants registered through the Electronic Residency Application Service. PARTICIPANTS: The 915 (36%) of 2577 total OBGYN applicants who responded to the survey. RESULTS: US allopathic medical students received fewer interview offers in 2021 (median 13 [interquartile range 9-19]) compared to 2020 (median 15 [interquartile range 11-20]). There was no difference in the absolute numbers of interviews completed. A United States Medical Licensing Exam Step 1 score ≥221 resulted in more than a five-fold increase in adjusted odds of receiving at least 12 interviews for allopathic students. Black or African American US allopathic seniors had a 2.3 odds ratio for receiving at least 12 interview invitations compared to White non-Hispanic or Latino US allopathic seniors, adjusted for Step 1 score and the number of programs applied to. Interview offers released on standardized dates had a mitigating effect on completing more interviews among allopathic seniors with at least 12 interview invitations. CONCLUSIONS: Virtual interviews did not change the overall number of interviews completed. Standardization of interview offer dates mitigated excessive virtual interviewing, yet additional measures are needed to curb interview inflation and the effects on interview distributions.

Perspectives of Stakeholders About an Early Result Acceptance Program to Complement the Residency Match in Obstetrics and Gynecology.

Importance: The residency application process is flawed, costly, and distracts from the preparation for residency. Disruptive change is needed to improve the inefficiencies in current selection processes. Objective: To determine interest in an early result acceptance program (ERAP) among stakeholders in obstetrics and gynecology (OBGYN), and to estimate its outcome in future application cycles. Design, Setting, and Participants: Surveys of stakeholders in March 2021 queried interest in ERAP across the US. Respondents included OBGYN residency applicants, members of the Association of American Medical Colleges Group on Student Affairs, OBGYN clerkship directors, and residency program directors. Statistical analysis was performed from March to April 2021. Exposures: Respondents completed surveys sent by email from the Association of American Medical Colleges (to OBGYN applicants and members of the Group on Student Affairs), the Association of Professors of Gynecology and Obstetrics (to clerkship directors), and the Council on Resident Education in Obstetrics and Gynecology (to program directors). Main Outcomes and Measures: Applicants and program directors indicated their interest in participating in ERAP, and clerkship directors and members of the Group on Student Affairs indicated their likelihood of recommending ERAP using a 5-point Likert scale. Results: Respondents included 879 (34.0%) of 2579 applicants to OBGYN, 143 (50.3%) of 284 residency program directors, 94 (41.8%) of 225 clerkship directors, and 51 (32.9%) of 155 student affairs deans. The majority of respondents reported being either somewhat or extremely likely to participate in ERAP, including 622 applicants (70.7%) and 87 program directors (60.8%). Interest in ERAP was independent of an applicant's reported board scores, medical school type, race, number of applications submitted, or number of interviews completed. Among program directors, those at university programs were more likely to participate. Stakeholders supported a limit of 3 applications for ERAP, to fill 25% to 50% of residency positions. Estimating the outcome of ERAP using these data suggests 26 280 to 52 560 fewer applications could be submitted in the regular match cycle. Conclusions and Relevance: Stakeholders in the OBGYN application process expressed broad support for the concept of ERAP. The majority of applicants and programs indicated that they would participate, with potentially substantial positive impact on the application process. Careful pilot testing and research regarding implementation are essential to avoid worsening an already dysfunctional application process.

Building an Equitable Surgical Training Pipeline: Leadership Exposure for the Advancement of Gender and Underrepresented Minority Equity in Surgery (LEAGUES).

OBJECTIVE: Underrepresented minority (URM) medical students face many educational challenges. Barriers include lack of equitable representation, scarce mentorship, and the effects of systemic racism. For students interested in diversity and health equity, perceptions of surgical culture may discourage pursuing surgical specialties. We describe a national pilot for a novel surgical pipeline program, Leadership Exposure for the Advancement of Gender and Underrepresented Minority Equity in Surgery (LEAGUES), which utilizes early exposure, mentorship, and community building to empower URM students in pursuit of academic surgical careers. DESIGN: A 4-week virtual program included pairing students with faculty research mentors, virtual skills sessions, and seminars on leadership, advocacy, and career development. Participants underwent semi-structured interviews before and after participation, assessing experiences with mentorship and research, interest in surgery, career aspirations, and perceived barriers to career goals. SETTING: Department of Surgery, Michigan Medicine, Ann Arbor, Michigan. PARTICIPANTS: Rising second-year medical students. RESULTS: All 3 participants were Latinx; 2 were first-generation college students. Participants had no surgical mentorship and limited research exposure, citing a desire to learn research methodology, connect with mentors, and build towards a career working with underserved communities as motivating factors for participation. Perceived barriers to a surgical career included surgical culture, burnout, and lack of research expertise or academic network necessary for success. At completion of the program, participants described several themes: (1) new positive perspective on academic surgical culture, (2) interest and confidence in research, (3) hope for improving health disparities, (4) networking and longitudinal mentorship connections contributing to a sense of surgical community, and (5) eagerness to share resources with colleagues at their home institutions. CONCLUSIONS: LEAGUES program participants acquired tools and motivation to pursue careers in surgery, and established valuable longitudinal network and mentor relationships. LEAGUES is a novel model for national surgical pipeline programs.

Can Standardized Dates for Interview Offers Mitigate Excessive Interviewing?

OBJECTIVE: To determine the impact of specialty-specific guidelines for standardized interview offers on residency applicant behavior towards excessive interviewing. DESIGN: In 2019 to 2020, the Association of Professors of Gynecology and Obstetrics and the Council on Resident Education in Obstetrics and Gynecology (OBGYN) outlined standard dates for residency interview offers. A cross-sectional survey of applicants queried adherence to standardized interview offers, the number of interviews offers received, interviews completed, and application characteristics. Based on data that applicants in OBGYN with a mean number of 12 contiguous ranks are highly likely to match, factors associated with accepting an excessive percentage of interview offers were investigated in applicants with at least 12 interviews, using multiple logistic regression. SETTING: All OBGYN applicants were sent an anonymous electronic survey distributed through the Electronic Residency Application Service in February 2020, with the subset of US MD senior respondents selected for this analysis. PARTICIPANTS: There were a total of 1292 US MD senior applicants into OBGYN in 2020, with 505 (39%) providing their interview information through the survey. Three hundred and sixty (71%) of US MD senior respondents received at least 12 interviews. RESULTS: Applicants receiving at least 12 interview offers completed a median of 83% of their interviews, and excessive interviewing was defined as completing greater than this median percentage. Receiving most interview offers on standardized interview offer dates resulted in less excessive interviewing despite controlling for number of programs applied to, applying as a couple, and United States Medical Licensing Exams Step 1 score. CONCLUSIONS: The standardization of interview offer dates may mitigate interview inflation by altering applicant behavior. This promising pilot data suggests that applicants may be able to make more informed decisions about which interview offers to accept when all offers are received on predetermined dates.

Fostering Passion and Skills in Surgical Research Across the Medical Education Continuum: The Transplant Research, Education, and Engagement Group.

OBJECTIVE: We describe a multilevel, collaborative research group for trainees and faculty engaging in transplant surgery research within one institution. DESIGN: Transplant Research, Education, and Engagement (TREE) was designed to develop trainees' research skills and foster enthusiasm in transplant surgery along the educational continuum. Our research model intentionally empowers junior researchers, including undergraduates and medical students, to assume active roles on a range of research projects and contribute new ideas within a welcoming research and learning environment. SETTING: Section of Transplant Surgery, Department of Surgery, Michigan Medicine, Ann Arbor, Michigan. PARTICIPANTS: Undergraduate premedical students, first through fourth year medical students, general surgery residents, transplant surgery fellows, and transplant surgery faculty. RESULTS: TREE was founded in September 2019 and has grown to include over 30 active members who meet weekly and collaborate virtually on a range of research projects, many of which are led by students. Trainees can assume both mentee and mentor roles and build their research, presentation and writing skills while collaborating academically. CONCLUSIONS: Our model has increased trainees' engagement in transplant research projects and fosters early enthusiasm for the field. This model can be feasibly replicated at other institutions and within other subspecialties.

Habitual aerobic exercise and circulating proteomic patterns in healthy adults: relation to indicators of healthspan.

Habitual aerobic exercise enhances physiological function and reduces risk of morbidity and mortality throughout life, but the underlying molecular mechanisms are largely unknown. The circulating proteome reflects the intricate network of physiological processes maintaining homeostasis and may provide insight into the molecular transducers of the health benefits of physical activity. In this exploratory study, we assessed the plasma proteome (SOMAscan proteomic assay; 1,129 proteins) of healthy sedentary or aerobic exercise-trained young women and young and older men ( n = 47). Using weighted correlation network analysis to identify clusters of highly co-expressed proteins, we characterized 10 distinct plasma proteomic modules (patterns). In healthy young (24 ± 1 yr) men and women, 4 modules were associated with aerobic exercise status and 1 with participant sex. In healthy young and older (64 ± 2 yr) men, 5 modules differed with age, but 2 of these were partially preserved at young adult levels in older men who exercised; among all men, 4 modules were associated with exercise status, including 3 of the 4 identified in young adults. Exercise-linked proteomic patterns were related to pathways involved in wound healing, regulation of apoptosis, glucose-insulin and cellular stress signaling, and inflammation/immune responses. Importantly, several of the exercise-related modules were associated with physiological and clinical indicators of healthspan, including diastolic blood pressure, insulin resistance, maximal aerobic capacity, and vascular endothelial function. Overall, these findings provide initial insight into circulating proteomic patterns modulated by habitual aerobic exercise in healthy young and older adults, the biological processes involved, and their relation to indicators of healthspan. NEW & NOTEWORTHY This is the first study to assess the relation between plasma proteomic patterns and aerobic exercise status in healthy adults. Weighted correlation network analysis identified 10 distinct proteomic modules, including 5 patterns specific for exercise status. Additionally, 5 modules differed with aging in men, two of which were preserved in older exercising men. Exercise-associated modules included proteins related to inflammation, stress pathways, and immune function and correlated with clinical and physiological indicators of healthspan.