Interdisciplinary Implementation of a Synoptic Reporting Template for Melanoma Nodal Surveillance Ultrasound.

BACKGROUND: With nodal surveillance increasingly used for sentinel lymph node-positive (SLN+) melanoma following the Second Multicenter Selective Lymphadenectomy Trial (MSLT-II), high-quality nodal ultrasonography (U/S) has become a critical need. Previous work has demonstrated low utilization of MSLT-II U/S criteria to define abnormal lymph nodes requiring intervention or biopsy. To address this gap, an evidence-based synoptic template was designed and implemented in this single-center study. METHODS: Sentinel lymph node-positive patients undergoing nodal surveillance at a tertiary cancer center from July 2017 to June 2023 were identified retrospectively. Ultrasound reporting language was analyzed for MSLT-II criteria reported and clinically actionable recommendations (e.g., normal, abnormal with recommendation for biopsy). Following a multidisciplinary design process, the synoptic template was implemented in January 2023. Postimplementation outcomes were evaluated by using U/S reports and provider surveys. RESULTS: A total of 337 U/S studies were performed on 94 SLN+ patients, with a median of 3 U/S per patient (range 1-12). Among 42 synoptic-eligible U/S performed postimplementation, 32 U/S (76.0%) were reported synoptically. Significant increases were seen in the number of MSLT-II criteria reported (Pre 0.5 ± 0.8 vs. Post 2.5 ± 1.0, p < 0.001), and clinically actionable recommendations for abnormal findings (Pre 64.0% vs. Post 93.0%, p = 0.04). Nearly all surgeon and radiologist survey respondents were "very" or "completely" satisfied with the clinical utility of the synoptic template (90.0%). CONCLUSIONS: Following implementation of a synoptic template, U/S reports were significantly more likely to document MSLT-II criteria and provide an actionable recommendation, increasing usefulness to providers. Efforts to disseminate this synoptic template to other centers are ongoing.

CD8+ T cell-derived Fgl2 regulates immunity in a cell-autonomous manner via ligation of FcγRIIB.

The regulatory circuits dictating CD8+ T cell responsiveness versus exhaustion during anti-tumor immunity are incompletely understood. Here we report that tumor-infiltrating antigen-specific PD-1+ TCF-1- CD8+ T cells express the immunosuppressive cytokine Fgl2. Conditional deletion of Fgl2 specifically in mouse antigen-specific CD8+ T cells prolongs CD8+ T cell persistence, suppresses phenotypic and transcriptomic signatures of T cell exhaustion, and improves control of the tumor. In a mouse model of chronic viral infection, PD-1+ CD8+ T cell-derived Fgl2 also negatively regulates virus-specific T cell responses. In humans, CD8+ T cell-derived Fgl2 is associated with poorer survival in patients with melanoma. Mechanistically, the dampened responsiveness of WT Fgl2-expressing CD8+ T cells, when compared to Fgl2-deficient CD8+ T cells, is underpinned by the cell-intrinsic interaction of Fgl2 with CD8+ T cell-expressed FcγRIIB and concomitant caspase 3/7-mediated apoptosis. Our results thus illuminate a cell-autonomous regulatory axis by which PD-1+ CD8+ T cells both express the receptor and secrete its ligand in order to mediate suppression of anti-tumor and anti-viral immunity.

Gender-Diverse Youth with Turner Syndrome: Special Management Considerations.

Turner syndrome (TS) is a sex chromosome abnormality characterized by short stature and primary hypogonadism with increased risk for cardiovascular disease, osteopenia, metabolic syndrome, diabetes mellitus, abnormal liver enzymes, and impairment of nonverbal learning skills. Gender-diverse youth include youth who have a gender identity that is different from their sex assigned at birth. They have an increased risk of suicidality, which is decreased in those who receive gender-affirming care. There have been no prior reports on the association or management of gender-diverse youth with TS. We describe 3 cases of gender-diverse youth with TS that highlight the importance of discussing gender identity in patients with hypogonadism in need of sex hormone replacement. Goals of care should be discussed to determine whether estrogen or testosterone replacement aligns best with gender identity. If a patient chooses to start testosterone, special considerations of risks such as erythrocytosis, osteopenia, and cardiovascular disease should be discussed in relation to their TS.

Evaluation and medical care of intersex and gender diverse youth.

While there is considerable overlap in the treatment of patients with intersex traits and differences in sex development (I/DSD) with transgender and gender diverse (TGD) youth, the initial medical evaluation varies significantly. I/DSD youth often present due to differences in genitalia development in infancy or pubertal development in adolescence, and this leads to comprehensive biochemical, radiologic, and genetic evaluation. TGD youth, however, tend to have typical development noted at birth and during puberty, but present with a gender identity that does not align with their sex assigned at birth and do not require evaluation for underlying pathology. For both I/DSD and TGD youth, the mainstays of treatment are to better align one's physical appearance to their gender identity. This review discusses the non-medical and medical interventions utilized in gender affirming care. A multidisciplinary team of mental health providers, pediatric medical providers, and surgeons is recommended for providing gender affirming care to both I/DSD youth and TGD youth and their families. Radiologists have an important role in initial evaluation of I/DSD youth and in ongoing monitoring of growth and bone mineral density during puberty induction in I/DSD and TGD youth.

Decision-Making Confidence of Clinical Competency Committees for Entrustable Professional Activities.

Importance: A competency-based assessment framework using entrustable professional activities (EPAs) was endorsed by the American Board of Surgery following a 2-year feasibility pilot study. Pilot study programs' clinical competency committees (CCCs) rated residents on EPA entrustment semiannually using this newly developed assessment tool, but factors associated with their decision-making are not yet known. Objective: To identify factors associated with variation in decision-making confidence of CCCs in EPA summative entrustment decisions. Design, Setting, and Participants: This cohort study used deidentified data from the EPA Pilot Study, with participating sites at 28 general surgery residency programs, prospectively collected from July 1, 2018, to June 30, 2020. Data were analyzed from September 27, 2022, to February 15, 2023. Exposure: Microassessments of resident entrustment for pilot EPAs (gallbladder disease, inguinal hernia, right lower quadrant pain, trauma, and consultation) collected within the course of routine clinical care across four 6-month study cycles. Summative entrustment ratings were then determined by program CCCs for each study cycle. Main Outcomes and Measures: The primary outcome was CCC decision-making confidence rating (high, moderate, slight, or no confidence) for summative entrustment decisions, with a secondary outcome of number of EPA microassessments received per summative entrustment decision. Bivariate tests and mixed-effects regression modeling were used to evaluate factors associated with CCC confidence. Results: Among 565 residents receiving at least 1 EPA microassessment, 1765 summative entrustment decisions were reported. Overall, 72.5% (1279 of 1765) of summative entrustment decisions were made with moderate or high confidence. Confidence ratings increased with increasing mean number of EPA microassessments, with 1.7 (95% CI, 1.4-2.0) at no confidence, 1.9 (95% CI, 1.7-2.1) at slight confidence, 2.9 (95% CI, 2.6-3.2) at moderate confidence, and 4.1 (95% CI, 3.8-4.4) at high confidence. Increasing number of EPA microassessments was associated with increased likelihood of higher CCC confidence for all except 1 EPA phase after controlling for program effects (odds ratio range: 1.21 [95% CI, 1.07-1.37] for intraoperative EPA-4 to 2.93 [95% CI, 1.64-5.85] for postoperative EPA-2); for preoperative EPA-3, there was no association. Conclusions and Relevance: In this cohort study, the CCC confidence in EPA summative entrustment decisions increased as the number of EPA microassessments increased, and CCCs endorsed moderate to high confidence in most entrustment decisions. These findings provide early validity evidence for this novel assessment framework and may inform program practices as EPAs are implemented nationally.

Silicon Composite Anode Degradation during Freeze-Thaw Temperature-Swings.

Batteries used in space applications can be exposed to large temperature-swings. During these large temperature-swings, the battery electrolyte can undergo a phase transformation from a liquid to a solid and back to a liquid. The nature of the solvent and the type of salt influence the crystallization processes. Herein, we aim to understand how pressure build-up in confined regions of an electrode (e.g., pores) influences degradation processes in silicon-oxide graphite anodes undergoing freeze-thaw dynamics. Our results show that high porosity electrodes lead to a greater density of nucleation sites for electrolyte crystallization. Local pressure build-up at pores results in active material loss and decreased cycle lifetime in batteries exposed to extreme temperature swings.

Entrustable Professional Activities in Surgery: A Review.

Importance: Entrustable professional activities (EPAs) compose a competency-based education (CBE) assessment framework that has been increasingly adopted across medical specialties as a workplace-based assessment tool. EPAs focus on directly observed behaviors to determine the level of entrustment a trainee has for a given activity of that specialty. In this narrative review, we highlight the rationale for EPAs in general surgery, describe current evidence supporting their use, and outline some of the practical considerations for EPAs among residency programs, faculty, and trainees. Observations: An expanding evidence base for EPAs in general surgery has provided moderate validity evidence for their use as well as practical recommendations for implementation across residency programs. Challenges to EPA use include garnering buy-in from individual faculty and residents to complete EPA microassessments and engage in timely, specific feedback after a case or clinical encounter. When successfully integrated into a program's workflow, EPAs can provide a more accurate picture of residents' competence for a fundamental surgical task or activity compared with other assessment methods. Conclusions and Relevance: EPAs represent the next significant shift in the evaluation of general surgery residents as part of the overarching progression toward CBE among all US residency programs. While pragmatic challenges to the implementation of EPAs remain, the best practices from EPA and other CBE assessment literature summarized in this review may assist individuals and programs in implementing EPAs. As EPAs become more widely used in general surgery resident training, further analysis of barriers and facilitators to successful and sustainable EPA implementation will be needed to continue to optimize and advance this new assessment framework.

Circulating N-lactoyl-amino acids and N-formyl-methionine reflect mitochondrial dysfunction and predict mortality in septic shock.

INTRODUCTION: Sepsis is a highly morbid condition characterized by multi-organ dysfunction resulting from dysregulated inflammation in response to acute infection. Mitochondrial dysfunction may contribute to sepsis pathogenesis, but quantifying mitochondrial dysfunction remains challenging. OBJECTIVE: To assess the extent to which circulating markers of mitochondrial dysfunction are increased in septic shock, and their relationship to severity and mortality. METHODS: We performed both full-scan and targeted (known markers of genetic mitochondrial disease) metabolomics on plasma to determine markers of mitochondrial dysfunction which distinguish subjects with septic shock (n = 42) from cardiogenic shock without infection (n = 19), bacteremia without sepsis (n = 18), and ambulatory controls (n = 19) - the latter three being conditions in which mitochondrial function, proxied by peripheral oxygen consumption, is presumed intact. RESULTS: Nine metabolites were significantly increased in septic shock compared to all three comparator groups. This list includes N-formyl-L-methionine (f-Met), a marker of dysregulated mitochondrial protein translation, and N-lactoyl-phenylalanine (lac-Phe), representative of the N-lactoyl-amino acids (lac-AAs), which are elevated in plasma of patients with monogenic mitochondrial disease. Compared to lactate, the clinical biomarker used to define septic shock, there was greater separation between survivors and non-survivors of septic shock for both f-Met and the lac-AAs measured within 24 h of ICU admission. Additionally, tryptophan was the one metabolite significantly decreased in septic shock compared to all other groups, while its breakdown product kynurenate was one of the 9 significantly increased. CONCLUSION: Future studies which validate the measurement of lac-AAs and f-Met in conjunction with lactate could define a sepsis subtype characterized by mitochondrial dysfunction.

Effectiveness of Hypertension Management Strategies in SPRINT-Eligible US Adults: A Simulation Study.

BACKGROUND: Despite reducing cardiovascular disease (CVD) events and death in SPRINT (Systolic Blood Pressure Intervention Trial), intensive systolic blood pressure goals have not been adopted in the United States. This study aimed to simulate the potential long-term impact of 4 hypertension management strategies in SPRINT-eligible US adults. METHODS AND RESULTS: The validated Blood Pressure Control-Cardiovascular Disease Policy Model, a discrete event simulation of hypertension care processes (ie, visit frequency, blood pressure [BP] measurement accuracy, medication intensification, and medication adherence) and CVD outcomes, was populated with 25 000 SPRINT-eligible US adults. Four hypertension management strategies were simulated: (1) usual care targeting BP <140/90 mm Hg (Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure usual care), (2) intensive care per the SPRINT protocol targeting BP <120/90 mm Hg (SPRINT intensive), (3) usual care targeting guideline-recommended BP <130/80 mm Hg (American College of Cardiology/American Heart Association usual care), and (4) team-based care added to usual care and targeting BP <130/80 mm Hg. Relative to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure usual care, among the 18.1 million SPRINT-eligible US adults, an estimated 138 100 total CVD events could be prevented per year with SPRINT intensive, 33 900 with American College of Cardiology/American Heart Association usual care, and 89 100 with team-based care. Compared with the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure usual care, SPRINT intensive care was projected to increase treatment-related serious adverse events by 77 600 per year, American College of Cardiology/American Heart Association usual care by 33 300, and team-based care by 27 200. CONCLUSIONS: As BP control has declined in recent years, health systems must prioritize hypertension management and invest in effective strategies. Adding team-based care to usual care may be a pragmatic way to manage risk in this high-CVD-risk population.

Validity of Entrustable Professional Activities in a National Sample of General Surgery Residency Programs.

BACKGROUND: The American Board of Surgery has endorsed competency-based education as vital to the assessment of surgical training. From 2018 to 2020, a national pilot study was conducted at 28 general surgery programs to evaluate feasibility of implementing entrustable professional activities (EPAs) for 5 common general surgical conditions. ACGME core competency Milestones were also rated for each resident by program clinical competency committees. This study aimed to evaluate the validity of general surgery EPAs compared with Milestones. STUDY DESIGN: Prospectively collected, de-identified EPA Pilot Study data were analyzed. EPAs studied were EPA-1 (gallbladder), EPA-2 (inguinal hernia), EPA-3 (right lower quadrant pain), EPA-4 (trauma), and EPA-5 (consult). Variables abstracted included levels of EPA entrustment (1 to 5) and corresponding ACGME Milestone subcompetency ratings (1 to 5) for the same study cycle. Spearman's correlations were used to evaluate the relationship between summative EPA scores and corresponding Milestone ratings. RESULTS: A total of 493 unique residents received a summative entrustment decision. EPA summative entrustment scores had moderate-to-strong positive correlation with mapped Milestone subcompetencies, with median rho value of 0.703. Among operation-focused EPAs, median rho values were similar between EPA-1 (0.688) and EPA-2 (0.661), but higher for EPA-3 (0.833). EPA-4 showed a strong positive correlation with diagnosis and communication competencies (0.724), whereas EPA-5, mapped to the most Milestone subcompetencies, had the lowest median rho value (0.455). CONCLUSIONS: Moderate-to-strong positive correlation was noted between EPAs and patient care, medical knowledge, and communication Milestones. These findings support the validity of EPAs in general surgery and suggest that EPA assessments can be used to inform Milestone ratings by clinical competency committees.

Racial and Ethnic Disparities in Operative Experience Among General Surgery Residents: A Multi-Institutional Study from the US ROPE Consortium.

OBJECTIVE: To determine the relationship between race/ethnicity and case volume among graduating surgical residents. BACKGROUND: Racial/ethnic minority individuals face barriers to entry and advancement in surgery; however, no large-scale investigations of the operative experience of racial/ethnic minority residents have been performed. METHODS: A multi-institutional retrospective analysis of the Accreditation Council for Graduate Medical Education case logs of categorical general surgery residents at 20 programs in the US Resident OPerative Experience Consortium database was performed. All residents graduating between 2010 and 2020 were included. The total, surgeon chief, surgeon junior, and teaching assistant case volumes were compared between racial/ethnic groups. RESULTS: The cohort included 1343 residents. There were 211 (15.7%) Asian, 65 (4.8%) Black, 73 (5.4%) Hispanic, 71 (5.3%) "Other" (Native American or Multiple Race), and 923 (68.7%) White residents. On adjusted analysis, Black residents performed 76 fewer total cases (95% CI, -109 to -43, P <0.001) and 69 fewer surgeon junior cases (-98 to -40, P <0.001) than White residents. Comparing adjusted total case volume by graduation year, both Black residents and White residents performed more cases over time; however, there was no difference in the rates of annual increase (10 versus 12 cases per year increase, respectively, P =0.769). Thus, differences in total case volume persisted over the study period. CONCLUSIONS: In this multi-institutional study, Black residents graduated with lower case volume than non-minority residents throughout the previous decade. Reduced operative learning opportunities may negatively impact professional advancement. Systemic interventions are needed to promote equitable operative experience and positive culture change.

Health System Integration and Cancer Center Access for Rural Hospitals.

BACKGROUND: Cancer centers provide superior care but are less accessible to rural populations. Health systems that integrate a cancer center may provide broader access to quality surgical care, but penetration to rural hospitals is unknown. METHODS: Cancer center data were linked to health system data to describe health systems based on whether they included at least one accredited cancer center. Health systems with and without cancer centers were compared based on rural hospital presence. Bivariate tests and multivariable logistic regression were used with results reported as P-values and odds ratios (OR) with 95% confidence intervals (CIs). RESULTS: Ninety percent of cancer centers are in a health system, and 72% of health systems (434/607) have a cancer center. Larger health systems (P = .03) with more trainees (P = .03) more often have cancer centers but are no more likely to include rural hospitals (11% vs 6%, P = .43; adjusted OR .69, 95% CI .28-1.70). The minority of cancer centers not in health systems (N = 95) more often serve low complexity patient populations (P = .02) in non-metropolitan areas (P = .03). DISCUSSION: Health systems with rural hospitals are no more likely to have a cancer center. Ongoing health system integration will not necessarily expand rural patients' access to surgical care under existing health policy infrastructure and incentives.

Diabetes Stigma and Psychosocial Outcomes in Adolescents and Young Adults: The SEARCH for Diabetes in Youth Study.

OBJECTIVE: To examine the association between diabetes stigma, socioeconomic status, psychosocial variables, and substance use in adolescents and young adults (AYAs) with type 1 or type 2 diabetes. RESEARCH DESIGN AND METHODS: This is a cross-sectional analysis of AYAs from the SEARCH for Diabetes in Youth study who completed a survey on diabetes-related stigma, generating a total diabetes stigma score. Using multivariable modeling, stratified by diabetes type, we examined the relationship of diabetes stigma with variables of interest. RESULTS: Of the 1,608 AYAs who completed the diabetes-related stigma survey, 78% had type 1 diabetes, and the mean age was 21.7 years. Higher diabetes stigma scores were associated with food insecurity (P = 0.001), disordered eating (P < 0.0001), depressive symptoms (P < 0.0001), and decreased health-related (P < 0.0001) and diabetes-specific quality of life (P < 0.0001). CONCLUSIONS: Diabetes stigma is associated with food insecurity, disordered eating, and lower psychosocial well-being.

Contemporary trends in extent of surgery for differentiated thyroid cancer with extrathyroidal extension.

OBJECTIVE: Although lobectomy is acceptable for patients with small, low-risk differentiated thyroid cancer (DTC), gross extrathyroidal extension (ETE) remains an indication for total thyroidectomy (TT). Here we investigate evolving trends in extent of surgery for â€‹+ â€‹ETE DTC. METHODS: Patients with +ETE DTC who underwent resection from 2010 to 2020 were identified using the National Cancer Database. The primary outcome was performance of TT versus lobectomy. RESULTS: Among 5851 patients, most were female (79.7%), white (80.0%), and had minimal ETE (91.8%). Ninety-two percent of patients received TT. Year of treatment was influential (p â€‹< â€‹0.001), with increasing lobectomy rates in later years. On multivariable analyses, a decreased likelihood of TT was seen in years 2015 through 2020. CONCLUSIONS: Most patients with +ETE DTC underwent guideline-concordant TT, but lobectomy rates doubled over the study period. These findings may reflect increased preference for lobectomy in low-risk DTC, but could undertreat patients with high-risk features.

Effect of Remotely Supervised Weight Loss and Exercise Training Versus Lifestyle Counseling on Cardiovascular Risk and Clinical Outcomes in Older Adults With Rheumatoid Arthritis: A Randomized Controlled Trial.

OBJECTIVE: To compare a remotely supervised weight loss and exercise intervention to lifestyle counseling for effects on cardiovascular disease risk, disease activity, and patient-reported outcomes in older patients with rheumatoid arthritis (RA) and overweight/obesity. METHODS: Twenty older (60-80 years), previously sedentary participants with seropositive RA and overweight/obesity were randomized to 16 weeks of either Supervised Weight loss and Exercise Training (SWET) or Counseling Health As Treatment (CHAT). The SWET group completed aerobic training (150 minutes/week moderate-to-vigorous intensity), resistance training (two days/week), and a hypocaloric diet (7% weight loss goal). The CHAT control group completed two lifestyle counseling sessions followed by monthly check-ins. The primary outcome was a composite metabolic syndrome z-score (MSSc) derived from fasting glucose, triglycerides, high density lipoprotein-cholesterol, minimal waist circumference, and mean arterial pressure. Secondary outcomes included RA disease activity and patient-reported outcomes. RESULTS: Both groups improved MSSc (absolute change -1.67 ± 0.64 in SWET; -1.34 ± 1.30 in CHAT; P < 0.01 for both groups) with no between-group difference. Compared with CHAT, SWET significantly improved body weight, fat mass, Disease Activity Score-28 C-reactive protein, and patient-reported physical health, physical function, mental health, and fatigue (P < 0.04 for all between-group comparisons). Based on canonical correlations for fat mass, cardiorespiratory fitness, and leg strength, component-specific effects were strongest for (1) weight loss improving MSSc, physical health, and mental health; (2) aerobic training improving physical function and fatigue; and (3) resistance training improving Disease Activity Score-28 C-reactive protein. CONCLUSION: In older patients with RA and overweight/obesity, 16 weeks of remotely supervised weight loss, aerobic training, and resistance training improve cardiometabolic health, patient-reported outcomes, and disease activity. Less intensive lifestyle counseling similarly improves cardiovascular disease risk profiles, suggesting an important role for integrative interventions in the routine clinical care of this at-risk RA population.