Faculty Bibliography

Prader-Willi syndrome (PWS) is a rare genetic disorder marked by metabolic, endocrine, and behavioral challenges, with hyperphagia as a central feature contributing to significant health risks. Diazoxide choline extended-release (DCCR; VYKAT™ XR) is a once-daily adenosine triphosphate (ATP)-sensitive potassium channel activator recently approved for the treatment of hyperphagia in individuals with genetically confirmed PWS aged 4 years and older. As this novel therapy enters clinical practice, clinicians require practical guidance on appropriate use. This manuscript provides actionable recommendations for patient selection, baseline assessments, and strategies for optimizing comorbid conditions prior to initiation. Structured, weight-based dosing and titration protocols are outlined, along with recommendations for monitoring glycemia and edema and managing common adverse events (AEs), including hyperglycemia, peripheral edema, and rash. Special considerations are discussed for patients with diabetes, cardiopulmonary risk factors, and those on concomitant medications with potential drug-drug interactions. The guidance is informed by data from the phase 3 DESTINY-PWS program, long-term extension studies, and real-world clinical experience. Emphasis is placed on early identification and management of AEs and the importance of a multidisciplinary approach to care. These recommendations aim to support clinicians in safely and effectively incorporating DCCR into the management of PWS, improving outcomes for affected individuals. Ongoing research and real-world evidence will continue to refine best practices and address remaining gaps in knowledge.

OBJECTIVE:To develop, implement, and assess the utility of a standardized letter of evaluation (SLOE) for OBGYN residency applicants in the US. DESIGN/METHODS:OBGYN program directors (PDs) were surveyed over 2 consecutive years and asked to estimate the percentage of applicants submitting an SLOE and to indicate its helpfulness compared to traditional letters of recommendation. Sub-group analysis by program type was performed. In 2023, comments for improvement were collected and analyzed for themes using a large language model. SETTING/METHODS:OB/GYN residency programs in the United States. PARTICIPANTS/METHODS:OB/GYN PDs in the United States. RESULTS:The survey was completed by 254 of 293 (86.7%) of PDs in 2022 and 253/293 (86.3%) in 2023. From 2022 to 2023, there was no difference in the estimated percentage of applicants who submitted an SLOE to a program (median 50%-74%), though in 2023, university and combined university-community programs estimated receiving higher percentage of applicants submitting SLOEs compared to community and military programs (p < 0.001). Over the study period, the favorability of the SLOE improved, and feedback indicates a need for continued improvement in the SLOE process, including faculty development, standardization, and more honest assessment of applicants. CONCLUSIONS:An SLOE was submitted by most applicants to OBGYN residency programs. Iterative modification of the SLOE based on PD, applicant, and faculty advisor feedback is needed to assess its utility in the application process.

Stereotactic body radiotherapy (SBRT) is established as standard therapy for organ-confined prostate cancer (PC) based on 5-yr phase 2-3 outcomes, but 10-yr data are lacking. Here, we report 10-yr results of a trial conducted at 21 centers. Patients were treated from January 2008 to April 2010. SBRT was delivered on a noncoplanar robotic platform with real-time motion management, to a total dose of 40 Gy in five fractions. Adjuvant hormone therapy was not allowed. Late toxicities (>90 d) were assessed with Common Terminology Criteria for Adverse Events version 3 (CTCAE v3). Biochemical failure is defined as nadir+2. Relapses are defined as biochemical or clinical failure or salvage/systemic PC therapy. Out of 310 evaluable patients, median age 68 yr; 172 were low-risk (LR), and 138 patients were intermediate-risk (IR). Median follow-up was 9 yr. Ten-yr cumulative grade 3 gastrointestinal (GI) or genitourinary (GU) toxicities were 1.4% and 1.5% in the LR and IR cohorts, respectively. There were no grade 4-5 events observed. Ten year grade 2+ GI and GU toxicity rates were 2.1% and 14% respectively. Overall survival in 10 yr was 84%. Overall, relapse-free survival (RFS) was 90%; 94% in the LR cohort, 86% in the IR cohort, and 92% versus 77% in the favorable vs unfavorable intermediate subgroups. In this multi-institutional trial, the 10-yr follow-up demonstrates that prostate SBRT yields minimal toxicity and favorable RFS.

INTRODUCTION/BACKGROUND:Biliary strictures (BS) are a significant challenge, with malignant strictures frequently diagnosed at advanced stages, limiting curative options. Digital single-operator cholangioscopy (D-SOC) enables high-resolution, direct visualization of the bile duct, yet with suboptimal accuracy. Artificial intelligence (AI) has shown promise for detection and differentiation of BS in frame-level analysis and small clinical series. This study aimed to validate a deep learning model for AI-assisted D-SOC image analysis. METHODS:This multicenter study included 135 D-SOC exams from 129 patients (61 with malignant BS) across 14 centers in the United States, Brazil, Spain, Colombia, Australia, and Saudi Arabia. For each exam, up to 25 clinically relevant frames were selected and uploaded to a web-based platform for AI analysis. The model performed both detection and differentiation of BS: detection was assessed by comparing AI-generated bounding boxes with expert-defined annotations using intersection-over-union (IoU), while differentiation was benchmarked against histopathology. Performance metrics included accuracy, sensitivity, specificity, and positive and negative predictive values (PPV and NPV). RESULTS:At the patient level, malignant BS were identified with 86.0% accuracy, 84.1% sensitivity and 85.7% specificity, with an AUC of 0.904. The model demonstrated robust detection performance, achieving a mean IoU of 70.3%. Performance was maintained across demographic variables and centers. DISCUSSION/CONCLUSIONS:This first multicentric validation study demonstrates real-world performance of AI-assisted D-SOC analysis across multiples continents and devices, with robust accuracy for BS detection and differentiation. These findings support AI as an adjunctive tool in D-SOC, enhancing a more accurate evaluation of patients with indeterminate BS.

INTRODUCTION/BACKGROUND:Early lymph node (LN) metastasis often precedes systemic metastasis and corresponds with significantly inferior survival for patients diagnosed with early-stage breast cancer (EBC). To understand the biological pathways involved in early LN metastasis, differential gene expression (DGE) analysis compared large tumors without evidence of LN metastasis (pT2-3pN0) to small tumors with LN metastasis (pT1pN+). METHODS:This study included 2,349 patients with EBC who underwent MammaPrint and BluePrint testing as part of the FLEX (NCT03053193). DGE was performed between pT2-3pN0/pT1pN + and across their MP/BP subtypes. Immune deconvolution was assessed using gene-signature-based methods, complemented by conventional tumor-infiltrating lymphocyte (TIL) analyses on a representative subset of patients. RESULTS:Greater DGE was observed within the MammaPrint High Risk and BluePrint Luminal B subgroups compared to pathological stages. MammaPrint High Risk tumors saw 73 differentially expressed genes (DEGs), while 34 were found for Luminal B tumors. Gene set enrichment analysis (GSEA) of MammaPrint High Risk/Luminal B tumors showed upregulated proliferation pathways and downregulated epithelial-to-mesenchymal transition (EMT) and immune profiles in pT2-3pN0 vs. pT1pN+, respectively. Immune deconvolution analyses showed a higher abundance of T gamma delta cells and CD4 + Th1 cells and a lower abundance of T regulatory cells, M2 macrophages, and cancer-associated fibroblasts within pT2-3pN0 tumors. Conventional histological assessment revealed no significant differences in TILs. CONCLUSION/CONCLUSIONS:This study lays the groundwork for exploring mechanisms of LN metastasis in EBC and their relation to MammaPrint High Risk and Luminal B subtypes. These data support previous studies' association of LN metastasis with EMT and immune dysregulation.

BACKGROUND AND AIMS/OBJECTIVE:The TRISCEND II trial demonstrated superior clinical benefits for patients with ≥severe tricuspid regurgitation (TR) treated with the EVOQUE transcatheter tricuspid valve replacement (TTVR) system plus medical therapy versus medical therapy alone. This work reports 1-year and 18-month outcomes in patients stratified by baseline TR severity. METHODS:The multicentre, prospective TRISCEND II trial enrolled 400 patients with symptomatic, ≥severe TR and randomised 2:1 to TTVR (n=267) or control (n=133). In a post-hoc analysis, patients were stratified into severe TR (n=172) and massive/torrential TR (n=220) cohorts. Clinical and quality-of-life outcomes were reported at 1 year, with Kaplan-Meier estimates for all-cause mortality and heart failure (HF) hospitalisation assessed at 18 months. Study oversight included an independent echocardiographic core laboratory, clinical events committee, and data safety monitoring board. RESULTS:One year after TTVR, TR was ≤mild in 95.2% of severe TR and 95.3% of massive/torrential TR patients. The primary safety and effectiveness endpoint (win ratio) favoured TTVR over control regardless of baseline TR severity: severe (1.64 [95% CI: 1.11, 2.43]) and massive/torrential (2.20 [1.55, 3.14]). At 18 months, TTVR patients had similar mortality to controls (rate difference: severe 0.2% [-11.6, 11.9], massive/torrential -5.8% [-17.6, 6.0], whereas HF hospitalisation rates favoured TTVR in the massive/torrential cohort (vs. control, severe 9.8% [-3.0, 22.7], massive/torrential -15.2% [-28.9, -1.5]). CONCLUSIONS:Patients with ≥severe TR benefit from TTVR, experiencing improvements in TR severity, functional capacity, and quality of life regardless of baseline TR severity, with a signal for greater benefit in patients with more advanced disease.

INTRODUCTION/BACKGROUND:Endoscopic retrograde cholangiopancreatography (ERCP) is essential for pancreaticobiliary disease management; however, there are risks associated with the procedure, particularly post-ERCP pancreatitis (PEP). Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), widely used in metabolic disease, possess anti-inflammatory and cytoprotective properties that may influence periprocedural outcomes. Their impact on ERCP adverse events remains unclear; therefore, we aimed to investigate whether GLP-1 influences short-term postprocedural outcomes using a large real-world database. METHODS:We conducted a retrospective cohort study using the TriNetX US Collaborative Network, identifying adults (18 y or older) who underwent ERCP between January 2015 and December 2024. Patients were categorized based on documented preprocedure GLP-1 receptor agonist exposure. Propensity score matching (1:1) was performed using demographic, clinical, procedural, and pharmacologic covariates to minimize confounding, yielding 2 well-balanced cohorts. Thirty-day post-ERCP outcomes-including acute pancreatitis, cholangitis, sepsis, gastrointestinal bleeding, biliary stricture, choledocholithiasis, and repeat ERCP-were assessed using ICD-10 and CPT codes. Risk ratios (RRs) and hazard ratios (HRs) with 95% CIs were calculated. RESULTS:Of 250,502 patients with ERCP screened, 21,818 propensity-matched individuals were included in the final analysis. Compared with matched nonusers, patients receiving GLP-1 receptor agonists had significantly lower 30-day rates of all major ERCP-related adverse events. GLP-1 RA exposure was associated with reduced risks of acute pancreatitis (RR: 0.47, 95% CI: 0.43-0.51), cholangitis (RR: 0.56, 95% CI: 0.50-0.62), sepsis (RR: 0.51, 95% CI: 0.46-0.57), gastrointestinal bleeding (RR: 0.49, 95% CI: 0.40-0.61), biliary stricture (RR: 0.52, 95% CI: 0.48-0.55), repeat ERCP (RR: 0.53, 95% CI: 0.48-0.58), and choledocholithiasis (RR: 0.66, 95% CI: 0.62-0.71). Results were consistent across time-to-event analyses over the 30-day follow-up period. CONCLUSIONS:In this large real-world analysis, preprocedure GLP-1 RA therapy was associated with markedly reduced 30-day ERCP-related adverse events, most notably PEP. These findings highlight a potential protective role of GLP-1 signaling in the periprocedural inflammatory response and support prospective studies evaluating GLP-1 RAs as adjunctive prophylactic agents in ERCP. Further prospective studies are needed.

The Patient-Oriented Eczema Measure (POEM) is a validated patient-reported outcome measure for atopic dermatitis (AD), though its use in routine pediatric dermatology practice remains underexplored. In this cross-sectional study of 297 pediatric patients with AD at a tertiary pediatric dermatology clinic, POEM scores were collected and compared with physician-rated investigator global assessment (IGA) and IGA × body surface area, as well as treatment selection. Older patients (> 12 years) had significantly higher mean POEM scores (17.5 vs. 10.4; p < 0.001) with no significant differences observed by race, ethnicity, or socioeconomic status; total POEM scores correlated strongly with IGA (r = 0.68) and moderately with IGA×BSA (r = 0.54), and higher severity scores were associated with more potent topical corticosteroids and systemic treatments (p < 0.001). POEM detected clinically relevant changes, aligned with physician-rated measures, and correlated with treatment intensity, underscoring its utility in both clinical practice and future predictive modeling applications.

This AM Last Page provides a visual depiction of how to best implement successful hybrid learning practices in academic -medicine using the Community of Inquiry conceptual framework.

BACKGROUND:Infection with the severe acute respiratory syndrome coronavirus-2 (SARSCoV-2), the virus which causes the corona virus disease-2019 (COVID-19) has substantial evidence that patients with pre-existing coronary artery disease (CAD) have an increased risk of serious illness, adverse coronary events, and mortality following infection. The COVID-CT registry will assess whether COVID-19 alters progression of coronary atherosclerotic plaque in patients with previously defined anatomic CAD on coronary computed tomographic angiography (CCTA). Mediators and covariates such as disease severity, inflammation, and neighborhood deprivation will also be assessed. DESIGN/METHODS:The COVID-CT registry is a multicenter, longitudinal observational registry enrolling patients including patients with pre-pandemic atherosclerosis observed by CCTA from New York City and Long Island to determine the impact of COVID-19 infection. The primary aim is to test the hypothesis that patients with previously defined anatomic CAD by CCTA who are subsequently infected with SARS-CoV-2 have accelerated progression of total and noncalcified atherosclerotic plaque volumes when compared to uninfected patients. We hypothesize that systemic inflammation is a key promoter in the formation and progression of atherosclerotic plaque. Additionally, we will test whether measurement of the perivascular fat attenuation index detects high risk, coronary artery inflammation following COVID infection. SUMMARY/CONCLUSIONS:The impact of this first in-kind registry will be foundational for revising standard diagnostic pathways and risk assessment used to guide preventive care for millions of patients with CAD at increased risk from viral infection.