Efficient synthesis for each of the eight stereoisomers of the iminosugars lentiginosine and 1,4-dideoxy-1,4-imino-D-arabinitol (DAB).

Herein, we describe the efficient, diastereoselective syntheses of the iminosugars 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) 1b, lentiginosine 3a, and the seven stereoisomers of each of these iminosugars starting from 4-benzoyl-6-deoxy-6-iodoglycopyranosides 47 with yields ranging from 38 % to 68 % for the DAB and isomers 1a-1h and from 44 % to 89 % for the lentiginosine and isomers 3a-3h. We also report the syntheses of the eight stereoisomers of the 4-benzoyl-6-deoxy-6-iodoglycopyranosides 47 from commercially available sugars. Key to the iminosugar syntheses is a single multistep reaction that converts the 4-benzoyl-6-deoxy-6-iodoglycopyranosides 47 to a vinyl pyrrolidine through a one-pot zinc mediated reductive elimination, followed by a reductive amination and finally an intramolecular nucleophilic substitution. Strategic selection of the amine utilized in the reductive amination and the functionalization of the intermediate carbon-carbon double bond provides access to a vast array of iminosugars.

Incidence of Pathologic Nodal Disease in Clinically Node-Negative, Microinvasive or T1a Breast Cancers.

BACKGROUND: Axillary staging in early-stage breast cancer can impact adjuvant treatment options but also has associated morbidity. The incidence of pathologic nodal positivity (pN+) in patients with microinvasive or T1a disease is poorly characterized and the value of sentinel node biopsy remains controversial. METHODS: Women with cN0 and pathologic microinvasive or T1a cancer who underwent upfront surgery were identified from the National Cancer Database. Pathologic nodal stage at the time of surgery was the primary outcome. Multivariable logistic modeling was used to assess predictors of pN+. RESULTS: Overall, 141,840 women were included; 139,206 had pathologic node-negative (pN0) disease and 2634 had pN+ disease. Rates of pN+ disease differed by receptor status, with the highest rates in hormone receptor-negative/human epidermal growth factor receptor 2-positive (HR-/HER2+) disease compared with triple-negative breast cancer (TNBC), HR-positive/HER2-negative (HR+/HER2-), and triple positive breast cancer. Rates of pN+ were also higher with lobular histology compared with ductal histology. Multivariable analysis demonstrated that compared with White women, Black women had higher odds of pN+ disease, and compared with women <50 years of age, women >70 years of age had higher odds of pN+ disease. Compared with women with HR+/HER2- disease, women with TNBC, triple-positive breast cancer, and HR-/HER2+ all had lower odds, and women with invasive lobular disease had higher odds compared with women with invasive ductal disease. Women with significant comorbidities also had higher odds of node positivity. CONCLUSION: Over 90% of patients with clinically node-negative, microinvasive and T1a breast cancer remain pathologically node-negative following axillary staging. However, higher rates of nodal disease were found among Black patients, older patients, and patients with lobular cancer and significant comorbidities.

Cultural Competency Curricula in US Graduate Medical Education: A Scoping Review.

BACKGROUND: Cultural competency training provides participants with knowledge and skills to improve cross-cultural communication and is required for all graduate medical education (GME) training programs. OBJECTIVE: The authors sought to determine what cultural competency curricula exist specifically in GME. METHODS: In April 2020, the authors performed a scoping review of the literature using a multidatabase (PubMed, Ovid, MedEdPORTAL) search strategy that included keywords relevant to GME and cultural competency. The authors extracted descriptive data about the structure, implementation, and analysis of cultural competency curricula and analyzed these data for trends. RESULTS: Sixty-seven articles met criteria for inclusion, of which 61 (91%) were focused exclusively on residents. The most commonly included specialties were psychiatry (n=19, 28.4%), internal medicine (n=16, 23.9%), and pediatrics (n=15, 22.4%). The shortest intervention was a 30-minute online module, while the longest contained didactics, electives, and mentoring programs that spanned the entirety of residency training (4 years). The sample sizes of included studies ranged from 6 to 833 participants. Eight (11.9%) studies utilized OSCEs as assessment tools, while 17 (25.4%) conducted semi-structured interviews or focus groups. Four common themes were unique interventions, retention of learning, trainee evaluation of curricula, and resources required for implementation. CONCLUSIONS: Wide variation exists in the design, implementation, and evaluation of cultural competency curricula for residents and fellows.

Perceived Discrimination Among Surgical Residents at Academic Medical Centers.

BACKGROUND: Residents of color experience microaggressions in the work environment, are less likely to feel that they fit into their training programs, and feel less comfortable asking for help. Discrimination has been documented among surgical residents, but has not been extensively studied and largely remains unaddressed. We sought to determine the extent of perceived discrimination among general surgery residents. MATERIALS AND METHODS: Residents who were enrolled in a randomized controlled trial investigating a cultural dexterity curriculum completed baseline assessments prior to randomization that included demographic information and the Everyday Discrimination Scale (EDS). Data from the baseline assessments were analyzed for associations of EDS scores with race, ethnicity, sex, socioeconomic level, language ability, and training level. RESULTS: Of 266 residents across seven residency programs, 145 (55%) were men. Racial breakdown was 157 (59%) White, 45 (17%) Asian, 30 (11%) Black, and 12 (5%) Multiracial. The median EDS score was seven (range: 0-36); 58 (22%) fell into the High EDS score group. Resident race, fluency in a language other than English, and median household income were significantly associated with EDS scores. When controlling for other sociodemographic factors, Black residents were 4.2 (95% CI 1.62-11.01, P = 0.003) times as likely to have High EDS scores than their White counterparts. CONCLUSIONS: Black surgical residents experience high levels of perceived discrimination on a daily basis. Institutional leaders should be aware of these findings as they seek to cultivate a diverse surgical training environment.

How Protective are Nipple-Sparing Prophylactic Mastectomies in BRCA1 and BRCA2 Mutation Carriers?

BACKGROUND: Nipple-sparing mastectomy (NSM) is now routinely offered to BRCA mutation carriers for risk reduction. We assessed the rates of ipsilateral cancer events after prophylactic and therapeutic NSM in BRCA1 and BRCA2 mutation carriers. METHODS: BRCA1 and BRCA2 mutation carriers undergoing NSM from October 2007 to June 2019 were identified in a single-institution prospective database, with variants of unknown significance being excluded. Patient, tumor, and outcomes data were collected. Follow-up analysis was by cumulative breast-years (total years of follow-up of each breast) and woman-years (total years of follow-up of each woman). RESULTS: Overall, 307 BRCA1 and BRCA2 mutation carriers (160 BRCA1, mean age 41.4 years [range 21-65]; and 147 BRCA2, mean age 43.8 years [range 23-65]) underwent 607 NSMs, with a median follow-up of 42 months (range 1-143). 388 bilateral prophylactic NSMs had 744 cumulative woman-years of follow-up, with no new cancers seen (< 0.0013 new cancers per woman-years); 251 BRCA1 prophylactic NSMs had 1034 cumulative breast-years of follow-up, with no new ipsilateral cancers seen (< 0.0010 per breast-year); 66 BRCA1 therapeutic NSMs had 328 cumulative breast-years of follow-up, with one ipsilateral cancer recurrence not directly involving the nipple or areola (0.0030 per breast-year); 237 BRCA2 prophylactic NSMs had 926 cumulative breast-years of follow-up, with no new ipsilateral cancers seen (< 0.0011 per breast-year); and 53 BRCA2 therapeutic NSMs had 239 cumulative breast-years of follow-up, with two ipsilateral recurrent cancers, neither of which directly involved the nipple or areola (0.0084 per breast-year). CONCLUSIONS: The risk of new ipsilateral breast cancers is extremely low after NSM in BRCA1 and BRCA2 mutation carriers. NSM is an effective risk-reducing strategy for BRCA gene mutations.

Variations in the Delivery of Emergency General Surgery Care in the Era of Acute Care Surgery.

BACKGROUND: Acute care surgery (ACS) was proposed to improve emergency general surgery (EGS) care; however, the extent of ACS model adoption in the United States is unknown. A national survey was conducted to ascertain factors associated with variations in EGS models of care, with particular focus on ACS use. METHODS: A hybrid mail/electronic survey was sent in 2015 to 2,811 acute care hospitals with an emergency room and an operating room. If a respondent indicated that the approach to EGS was a dedicated clinical team whose scope encompasses EGS (± trauma, ± elective general surgery, ± burns), the hospital was considered an ACS hospital. RESULTS: Survey response was 60.1% (n = 1,690); 272 (16.1%) of these hospitals reported having used an ACS model of care for EGS patients. Teaching status and general hospital practices (for example, interventional radiology available within one hour) were associated with ACS use. In bivariate analyses, ACS use was associated with many EGS-specific practices (40.1% of ACS hospitals freed their surgeons of daytime clinical responsibilities after operating overnight vs. 4.7% of general surgeon on call (GSOC) hospitals; p < 0.0001). CONCLUSION: There are wide variations in EGS practices in the United States, with use of an ACS model of care being relatively low despite reported benefits of ACS models of care on EGS access, quality, and costs. Hospital factors associated with using ACS models are overall size and higher level of existing resources. These findings could be applied to the development of centers of excellence for EGS care.

Geographic Diffusion and Implementation of Acute Care Surgery: An Uneven Solution to the National Emergency General Surgery Crisis.

Importance: Owing to lack of adequate emergency care infrastructure and decline in general surgery workforce, the United States faces a crisis in access to emergency general surgery (EGS) care. Acute care surgery (ACS), an organized system of trauma, general surgery, and critical care, is a proposed solution; however, ACS diffusion remains poorly understood. Objective: To investigate geographic diffusion of ACS models of care and characterize the communities in which ACS implementation is lagging. Design, Setting, and Participants: A national survey on EGS practices was developed, tested, and administered at all 2811 US acute care hospitals providing EGS to adults between August 2015 and October 2015. Surgeons responsible for EGS coverage at these hospitals were approached. If these surgeons failed to respond to the initial survey implementation, secondary surgeons or chief medical officers at hospitals with only 1 general surgeon were approached. Interventions: Survey responses on ACS implementation were linked with geocoded hospital data and national census data to determine geographic diffusion of and access to ACS. Main Outcomes and Measures: We measured the distribution of hospitals with ACS models of care vs those without over time (diffusion) and by US counties characterized by sociodemographic characteristics of county residents (access). Results: Survey response rate was 60% (n = 1690); 272 responding hospitals had implemented ACS by 2015, steadily increasing from 34 in 2001 to 125 in 2010. Acute care surgery implementation has not been uniform. Rural regions have limited ACS access, with hospitals in counties with greater than the 75th percentile population having 5.4 times higher odds (95% CI, 1.66-7.35) of implementing ACS than hospitals in counties with less than 25th percentile population. Communities with greater percentages of adults without a college degree also have limited ACS access (OR, 3.43; 95% CI, 1.81-6.48). However, incorporating EGS into ACS models may be a potential equalizer for poor, black, and Hispanic communities. Conclusions and Relevance: Understanding and addressing gaps in ACS implementation across communities will be crucial to ensuring health equity for US residents experiencing general surgery emergencies.

Disparities in access to emergency general surgery care in the United States.

BACKGROUND: As fewer surgeons take emergency general surgery call and hospitals decrease emergency services, a crisis in access looms in the United States. We examined national emergency general surgery capacity and county-level determinants of access to emergency general surgery care with special attention to disparities. METHODS: To identify potential emergency general surgery hospitals, we queried the database of the American Hospital Association for "acute care general hospital," with "surgical services," and "emergency department," and ≥1 "operating room." Internet search and direct contact confirmed emergency general surgery services that covered the emergency room 7 days a week, 24 hours a day. Geographic and population-level emergency general surgery access was derived from Geographic Information Systems and US Census. RESULTS: Of the 6,356 hospitals in the 2013 American Hospital Association database, only 2,811 were emergency general surgery hospitals. Counties with greater percentages of black, Hispanic, uninsured, and low-education individuals and rural counties disproportionately lacked access to emergency general surgery care. For example, counties above the 75th percentile of African American population (10.2%) had >80% odds of not having an emergency general surgery hospital compared with counties below the 25th percentile of African American population (0.6%). CONCLUSION: Gaps in access to emergency general surgery services exist across the United States, disproportionately affecting underserved, rural communities. Policy initiatives need to increase emergency general surgery capacity nationwide.

RAHI-SATHI Indo-U.S. Collaboration: The Evolution of a Trainee-Led Twinning Model in Global Health Into a Multidisciplinary Collaborative Program.

BACKGROUND: In recent years there has been a surge in the number of global health programs operated by academic institutions. However, most of the existing programs describe partnerships that are primarily faculty-driven and supported by extramural funding. PROGRAM DESCRIPTION: Research and Advocacy for Health in India (RAHI, or "pathfinder" in Hindi) and Support and Action Towards Health-Equity in India (SATHI, or "partnership" in Hindi) are 2 interconnected, collaborative efforts between the University of Massachusetts Medical School (UMMS) and Charutar Arogya Mandal (CAM), a medical college and a tertiary care center in rural western India. The RAHI-SATHI program is the culmination of a series of student/trainee-led research and capacity strengthening initiatives that received institutional support in the form of faculty mentorship and seed funding. RAHI-SATHI's trainee-led twinning approach overcomes traditional barriers faced by global health programs. Trainees help mitigate geographical barriers by acting as a bridge between members from different institutions, garner cultural insight through their ability to immerse themselves in a community, and overcome expertise limitations through pre-planned structured mentorship from faculty of both institutions. Trainees play a central role in cultivating trust among the team members and, in the process, they acquire personal leadership skills that may benefit them in their future careers. CONCLUSION: This paradigm of trainee-led twinning partnership promotes sustainability in an uncertain funding climate and provides a roadmap for conducting foundational work that is essential for the development of a broad, university-wide global health program.