Faculty Bibliography

BACKGROUND:The number of graduates from accelerated 3-year MD (A3YP) programs has increased over the past decade. Previous work showed that A3YP graduates perform comparably to non-accelerated (4-year) graduates from the same medical schools on mid-year and end-year Accreditation Council of Graduate Medical Education (ACGME) harmonized milestones. In shifting to the residency program perspective, it remains unclear how the performance of A3YP graduates compares to non-accelerated graduates including traditional 4-year, international, and osteopathic medical school graduates. OBJECTIVE:To compare the intern performance of A3YP graduates compared with non-accelerated graduates using mid-year and end-year ACGME milestones in Internal Medicine (IM) residency programs. DESIGN/METHODS:The study employed a retrospective cohort design, hypothesizing that graduates from A3YPs were comparable to non-accelerated graduates in the same program. PARTICIPANTS/METHODS:108 interns who graduated from A3YP were compared to 3,542 interns from non-accelerated programs at the same 34 IM residency programs. MAIN MEASURES/METHODS:Descriptive statistics were provided for ACGME milestone performance. Cross-classified random-effects regression was used to account for residency program effects and estimate group differences. KEY RESULTS/RESULTS:After controlling for residency programs, the milestone ratings of A3YP graduates were higher in all competency domains at mid-year except practice-based learning and improvement (PBLI) at .04 (P = .089) (coefficients ranged from 0.08 for medical knowledge (MK) (P < .001) to 0.23 in professionalism (PROF) (P < .001)). These differences persisted at the end-year period (coefficients ranged from 0.05 in PBLI (P = .039) to 0.17 in PROF (P < .001)) except MK at .02 (P = .656). Patient care differences were 0.15 (P < .001) at mid- and 0.14 (P = .005) at end-year. CONCLUSIONS:This study contributes to the literature demonstrating that interns graduating from A3YP are at least equivalent in terms of milestone assessment and possibly better in the competencies of PC and PROF than their non-accelerated counterparts.

BACKGROUND/UNASSIGNED:Endocrine findings in premature adrenarche have been characterized by elevated DHEAS levels in the past. METHODS/UNASSIGNED:We reviewed 44 female patients, aged 4 to 8 years, with premature adrenarche who were seen at our center between 2019 and 2023. Data were collected on the traditional androgens (DHEA and DHEAS) and novel 11-oxo-androgens. 11-oxo-androgens, DHEAS, and DHEA levels were measured using Liquid chromatography/tandem mass spectrometry (LC/MS-MS) assays in commercial laboratories (Lab Corp). RESULTS/UNASSIGNED:The majority, 89% of patients from the youngest group (4-5year olds), presented with apocrine odor as the only symptom of premature adrenarche. We have demonstrated that DHEA and DHEAS levels were within the normal range in many girls with premature adrenarche, whereas 11-oxo-androgens, particularly 11-hydroxyandrostenedione and 11β-hydroxytestosterone, were elevated. Out of those with normal DHEAS, 75 % had elevated 11-hydroxyandrostenedione, and 77.8% of those patients with normal DHEA had the same elevated oxo-adrogen. Additionally, advanced bone age greater than 1 year compared to chronological age was positively associated with 11-ketotestosterone (Spearman correlation coefficient = 0.32, 95% CI: 0.01-0.57, p=0.0429) and 11β-hydroxy testosterone (Spearman correlation coefficient=0.32, 95% CI: 0.01-0.58, p=0.0395). CONCLUSION/UNASSIGNED:We propose that 11-oxoandrogens are a more sensitive steroid to be measured in premature adrenarche.

OBJECTIVE:Exposure to antidepressants, particularly agents that work through serotonin-reuptake inhibition, may increase potential for bleeding, especially among patients with other bleeding risk factors. There is limited guidance for clinicians in the use of serotonin reuptake inhibitors (SRIs) and other antidepressants in the setting of increased bleeding risk. METHODS:A PubMed literature search was conducted for English-language articles (1992-2024) examining the bleeding risk associated with antidepressants. Physicians from the Association of Medicine and Psychiatry then convened to develop consensus recommendations. RESULTS:Consensus recommendations were established for managing antidepressant use in patients with medical and psychiatric comorbidities. Additionally, a clinical decision algorithm was created to assist clinicians in assessing the appropriateness of antidepressant prescribing in patients at risk for bleeding. CONCLUSIONS:The proposed algorithm can aid clinicians in determining whether antidepressant (including SRI) initiation, discontinuation, or dose adjustment should be considered for patients susceptible to bleeding. These guidelines preserve a role for clinical judgment in selection of treatments that balance the risks and benefits, which may be particularly relevant for patients with complex medical and psychiatric comorbidities. Additional studies are needed to better guide clinical decision making.

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:Accurate preoperative evaluation of pancreatic cysts is essential. However, cytology and biochemical analysis are often limited by low cellularity, and risk stratification is critical for management. PancreaSeq Genomic Classifier (GC) analyzes cyst fluid for molecular alterations to aid diagnosis and risk assessment. MATERIALS AND METHODS/METHODS:We retrospectively analyzed 219 pancreatic cysts from 206 patients using PancreaSeq GC, integrating molecular findings with cytology, biochemical, imaging, surgical pathology, and follow-up. RESULTS:PancreaSeq GC successfully analyzed 216/219 cysts (99%) and detected alterations in 182 (83%). Among cases with both cytology and molecular data (n = 201), concordance was high in cytologically mucinous neoplasms (94%) and atypical cases (95%). Notably, among cases reported as negative for malignancy or nondiagnostic on cytology (n = 128), PancreaSeq GC identified mucinous neoplasms in 82 cases (64%), demonstrating added value in limited samples. Surgical pathology correlation (n = 24) showed excellent performance for distinguishing mucinous from nonmucinous cysts (area under the curve [AUC] = 0.94, P < 0.001). Risk stratification for detection of any dysplasia yielded an AUC of 0.78 (P = 0.006), and for high-grade dysplasia an AUC of 0.74 (P = 0.046). PancreaSeq GC reliably predicted neuroendocrine tumors, but the sensitivity for focal high-grade dysplasia in mucinous neoplasms and serous cystadenoma was limited. Compared with carcinoembryonic antigen (CEA), cyst fluid glucose showed higher sensitivity but lower specificity for mucinous cyst detection. CONCLUSIONS:PancreaSeq GC provides significant diagnostic and risk-stratification value that complements cytological evaluation, particularly in indeterminate or nondiagnostic cytology specimens and when biochemical data are unavailable. Integration of molecular findings improves cyst classification and dysplasia risk assessment. Multidisciplinary assessment remains essential, given the assay's limited sensitivity for focal high-grade dysplasia and serous cystadenomas.

BACKGROUND:2-octyl cyanoacrylate (2-OCA) topical skin adhesives are widely used for surgical wound closure but are increasingly associated with allergic contact dermatitis (ACD). We conducted a systematic review and meta-analysis to define the incidence, clinical features, and risk factors for 2-OCA-associated ACD. STUDY DESIGN/METHODS:A PRISMA systematic review of PubMed, Embase, and Web of Science (2008-2025) identified studies reporting cutaneous hypersensitivity to 2-OCA in human wound closure. Randomized, observational, and case-based reports were included. Risk of bias was assessed using ROBINS-I and RoB 2. Incidence from analytic cohorts was pooled using a random-effects model with prespecified subgroup analyses by surgical specialty. RESULTS:Seventy-four studies comprising 26,330 exposed patients were included; 20 analytic cohorts (25,442 patients) contributed to meta-analysis. The pooled ACD incidence was 4% (95% CI 3-5%) with substantial heterogeneity (I²=94.5%; prediction interval 0-12%). Incidence was 4% in orthopedic cohorts and 8% in plastic surgery cohorts, with lower rates in dermatology and obstetrics/gynecology (p=0.015 for subgroup differences). Re-exposure markedly increased risk, with reaction rates rising from 1-3% after initial exposure to >20% in staged or repeat procedures in several cohorts. Prior adhesive/contact allergy and cosmetic acrylate exposure were also strong risk factors. Diagnosis was primarily clinical, with selective patch testing. Management typically involved adhesive removal and topical corticosteroids; systemic therapy was reserved for severe cases. CONCLUSIONS:ACD to 2-OCA is a clinically meaningful and likely under-recognized complication of surgical wound closure. Re-exposure is strongly associated with increased postoperative reaction rates, supporting preoperative risk assessment and caution in repeat adhesive use.

UNLABELLED:Inflammation, particularly mediated through interleukin-6 (IL-6) signaling, plays a critical role in stroke pathophysiology. High levels of IL-6 are associated with poor outcomes in stroke patients. Therapeutic inhibition of IL-6 signaling may offer a novel strategy to mitigate post-stroke damage and improve recovery. This study evaluated the efficacy of tocilizumab (TCZ), a clinically approved monoclonal antibody that blocks IL-6 receptor signaling, using data from the Stroke Preclinical Assessment Network (SPAN), a multi-center, randomized, blinded, placebo-controlled trial in preclinical stroke models. METHODS:We analyzed behavioral and MRI morphometry data from 701 rodents (both males and females; 1:1), including healthy young mice, diet-induced obese mice, aging mice, and spontaneously hypertensive rats (SHR) treated with saline (N = 348) or TCZ (N = 353) at a dose of 100 mg/kg for mice, 10 mg/kg for rats after middle cerebral artery occlusion (MCAO). RESULTS:In the overall mouse cohort, TCZ did not significantly improve long-term sensorimotor recovery or reduce brain tissue loss measured by MRI. However, aging mice exhibited modest motor function improvements. In SHRs, TCZ treatment resulted in improved sensory-motor function, particularly in male rats, as demonstrated by enhanced corner test scores on days 7 and 28 post-MCAO. While TCZ in SHRs provided early (day 2) cerebroprotection with reduced lesion volume, it did not alter subsequent tissue loss, as measured by tissue atrophy at day 30. CONCLUSIONS:These results suggest that IL-6R blockade with TCZ was associated with functional improvement in aging mice (modest) and hypertensive rats (notably males), without durable effect of brain tissue loss. No benefit was observed in the overall mouse cohort. These findings support IL-6 signaling as a viable therapeutic target and warrant further investigation into IL-6 receptor inhibition as a potential treatment strategy for stroke recovery.

OBJECTIVE:We discuss implications of potential ascertainment biases for studies examining diabetes risk following SARS-CoV-2 infection using electronic health records (EHRs). We quantitatively explore sensitivity of results to misclassification of COVID-19 status using data from the U.S.-based Diabetes in Children, Adolescents and Young Adults (DiCAYA) Network on children (≤17 years) and young adults (18-44 years). MATERIALS AND METHODS/METHODS:In our retrospective case study from the DiCAYA Network, SARS-CoV-2 was identified using labs and diagnoses from June 1, 2020 to December 31, 2021. Patients were followed through December 31, 2022 for new diabetes diagnoses. Sites examined incident diabetes by COVID-19 status using Cox proportional hazards models. Results were pooled in meta-analyses. A bias analysis examined potential impact of COVID-19 misclassification scenarios on results, guided by hypotheses that sensitivity would be <50% and would be higher among those who developed diabetes. RESULTS:Prevalence of documented COVID-19 was low overall and variable across sites (children: 4.4%-7.7%, young adults: 6.2%-22.7%). Individuals with documented COVID-19 were at higher risk of incident diabetes compared to those with no documented infection, but results were heterogeneous across sites. Findings were highly sensitive to COVID-19 misclassification assumptions. Observed results could be biased away from the null under several differential misclassification scenarios. DISCUSSION/CONCLUSIONS:Although EHR-based documentation of COVID-19 was associated with incident diabetes, COVID-19 phenotypes likely had low sensitivity, with considerable variation across sites. Misclassification assumptions strongly impacted interpretation of results. CONCLUSION/CONCLUSIONS:Given the potential for low phenotype sensitivity and misclassification, caution is warranted when interpreting analyses of COVID-19 and incident diabetes using clinical or administrative databases.