Faculty Bibliography

BACKGROUND:Perioperative immune-checkpoint inhibition improves outcomes in muscle-invasive bladder cancer (MIBC). The phase III, randomized CA017-078 (ENERGIZE) trial evaluated perioperative nivolumab plus neoadjuvant gemcitabine-cisplatin (GC) versus neoadjuvant GC alone for previously untreated, resectable MIBC. PATIENTS AND METHODS/METHODS:Adults with previously untreated cT2-T4aN0M0 MIBC eligible for radical cystectomy (RC) and cisplatin were randomized to neoadjuvant nivolumab plus GC followed by RC and adjuvant nivolumab (nivolumab plus GC arm), or neoadjuvant GC followed by RC alone (GC arm). Co-primary endpoints were pathological complete response (pCR; defined as ypT0N0) and event-free survival (EFS). Overall survival (OS) was a secondary endpoint within the prespecified hierarchical testing strategy, and formal testing was contingent on a statistically significant EFS result. RESULTS:At this final analysis with 54.5 months of median follow-up, 325 patients were randomized to the nivolumab plus GC arm, 328 to the GC arm. pCR rates were 39.1% and 29.6%, respectively (adjusted difference 9.5%, 99.91% CI -2.6-21.6). EFS was not improved in the nivolumab plus GC versus GC arm (104 events in each arm; HR 0.94, 95.74% CI 0.71-1.25; P=0.6697). OS was summarized descriptively because EFS did not meet the testing criterion (HR 0.88, 95% CI 0.64-1.21). Grade 3-4 treatment-related adverse events occurred in 50.0% versus 49.5%; one treatment-related death occurred with nivolumab plus GC. Pretreatment ctDNA was positive in 229/416 tested patients (55%) overall, 108/211 (51%) in the GC arm, and 121/205 (59%) in the nivolumab plus GC arm. Clearance by cycle 4 day 1 (C4D1) occurred in 153/199 patients (76.9%) overall, 87/107 (81.3%) with nivolumab plus GC, and 66/92 (71.7%) with GC. ctDNA detection at baseline and at C4D1 was associated with shorter EFS and OS. CONCLUSIONS:The addition of perioperative nivolumab to neoadjuvant GC did not improve outcomes and was associated with predictable toxicity. Exploratory analysis showed ctDNA was strongly prognostic.

IMPORTANCE/UNASSIGNED:Syringe services programs (SSPs) are an evidence-based intervention to reduce bloodborne disease transmission and other risks related to injection drug use; however, SSP access is uneven. State and local syringe distribution laws may influence variation in the presence and number of SSPs across local jurisdictions. OBJECTIVE/UNASSIGNED:To assess the association between state and local syringe distribution laws and presence of publicly listed SSPs in a sample of US cities. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cross-sectional study linked state and local laws with information on publicly reported SSPs in 2024 for the largest US municipalities and census-designated places (localities). The outcomes of policy exposure in SSP presence and total number of SSP locations among localities with at least 1 SSP were estimated using a 2-part negative binomial hurdle model, adjusting for state and local policy and demographic and health characteristics. The study team collected the legal data from January 11, 2023, through May 7, 2024. EXPOSURE/UNASSIGNED:State and local syringe distribution policy environment as of December 31, 2022, categorized from most restrictive (state prohibition) to least restrictive (neither state nor locality prohibits syringe distribution). MAIN OUTCOMES AND MEASURES/UNASSIGNED:Publicly reported SSP presence (binary) and total count of SSP locations within each locality as of February 2024. RESULTS/UNASSIGNED:In this study using data from 482 US localities, there was at least 1 SSP in 181 (37.6%) localities. Localities with the least restrictive legal environment had increased odds of SSP presence (adjusted odds ratio, 16.3; 95% CI, 6.0-44.1) compared with those with the most restrictive legal environment. Among localities with 1 or more SSP, localities in the least restrictive legal environment or a legal environment that exempted SSPs from a syringe distribution prohibition had increased rates of SSPs, relative to the most restrictive legal environment (rate ratio for least restrictive policy environment, 2.7; 95% CI, 1.1-6.4; rate ratio for legal environment that exempts SSPs from prohibition, 2.4; 95% CI, 1.1-5.6). Overall, policies that exempted SSPs from syringe distribution prohibitions and those with no syringe distribution prohibitions had the highest estimated SSP counts (1.9 SSPs; 95% CI, 1.5-2.4; 1.5 SSPs; 95% CI, 1.1-1.9, respectively). CONCLUSIONS AND RELEVANCE/UNASSIGNED:This study found that state and local syringe distribution laws were associated with publicly listed SSP presence. Legal environments that prohibit or restrict syringe distribution may limit the presence and total number of SSPs, highlighting the role of policy context in shaping access to harm-reduction services.

BACKGROUND/UNASSIGNED:Ulcerative colitis is monitored through clinical, laboratory, endoscopic, and histologic measures. Persistence of histologic inflammation despite clinical and endoscopic remission is associated with disease flare. METHODS/UNASSIGNED:We compared the identification of clinically significant histologic inflammation by general and IBD-specialized gastroenterologists (GI) using a simplified binary scoring system and looked at associations with disease relapse. RESULTS/UNASSIGNED:Both general and IBD-specialized GIs identified significant inflammation associated with relapse, though IBD-specialized GIs scoring had stronger correlations with relapse. CONCLUSIONS/UNASSIGNED:Our findings suggest simple histologic assessment can inform risk stratification, and further work is needed to optimize monitoring patients with histologic inflammation despite endoscopic remission.

INTRODUCTION/UNASSIGNED:Patients with Crohn's disease are at increased risk for both colorectal carcinoma and opportunistic infections due to chronic inflammation and long-term immunosuppressive therapy. Fungal infections such as histoplasmosis may mimic malignancy or inflammatory exacerbation, leading to diagnostic delay. CASE PRESENTATION/UNASSIGNED:, confirmed by polymerase chain reaction. The urinary Histoplasma galactomannan antigen test was negative, while serum 1,3 β-D-glucan was positive. The patient was successfully treated with amphotericin B followed by itraconazole, with complete clinical recovery. Retrospective history revealed travel to Ecuador. CONCLUSION/UNASSIGNED:Gastrointestinal histoplasmosis can closely mimic Crohn's flare or malignancy, especially in immunosuppressed patients. Careful histopathologic evaluation and integration of clinical and laboratory findings are essential for timely diagnosis and effective antifungal therapy.

Low-grade serous ovarian carcinoma (LGSOC) is a rare epithelial malignancy characterized by frequent mitogen-activated protein kinase (MAPK) pathway alterations, hormone receptor expression, relative resistance to cytotoxic chemotherapy, and a prolonged, relapsing clinical course. Since publication of the 2023 international expert consensus, significant advances have reshaped the management of both newly diagnosed and recurrent disease. The 2026 LGSOC Consensus Conference convened an international multidisciplinary panel of experts in the field to review emerging evidence and update recommendations across pathology, molecular testing, translational biology, frontline and recurrent treatment, imaging, treatment-associated toxicity, regulatory strategy, patient advocacy, and future research priorities. Recommendations were informed by contemporary clinical evidence, multidisciplinary discussion, and patient perspectives. The updated consensus incorporates practice-changing data from NRG-GY019 supporting chemotherapy-containing postoperative therapy as the current reference approach for stage II-IV disease while recognizing selected circumstances in which endocrine monotherapy may represent individualized de-escalation. It also integrates recent advances in recurrent disease, including the US Food and Drug Administration's accelerated approval of avutometinib in combination with defactinib for KRAS-mutated LGSOC, emerging evidence supporting endocrine therapy combined with CDK4/6 inhibition, and refined guidance for biomarker-directed treatment selection, imaging assessment, toxicity management, and patient-centered survivorship. The panel emphasizes treatment-specific biomarker interpretation, multidisciplinary care, central pathology review for clinical trials, and the continued need for prospective studies addressing treatment sequencing, predictive biomarkers, and quality-of-life outcomes. This updated international consensus provides an evidence-based framework for the diagnosis and management of LGSOC while identifying priorities for future clinical research and drug development.

OBJECTIVES/OBJECTIVE:To determine whether integrating an artificial intelligence (AI) decision-support system (VivoAID) into optical coherence tomography (OCT) interpretation improves diagnostic accuracy and efficiency for novice users evaluating basal cell carcinomas (BCCs). METHODS:Two dermatology research fellows completed a structured OCT training module for BCC identification using the VivoSight Dx system. Each independently reviewed 45 de-identified OCT scans (31 BCC-positive and 14 BCC-negative, negative ones included squamous cell carcinomas, keratoacanthomas, actinic keratoses and scar tissue), with ground truth established by expert clinical interpretation and histopathology, in two sessions: one unassisted and one AI-assisted. Session order was counterbalanced between learners, and scans were re-randomized for AI sessions. In unassisted sessions, learners manually classified scans; in AI-assisted sessions, they reviewed AI-annotated scans, recorded agreement/disagreement, and noted additional findings. Time-to-decision per scan was measured. A linear mixed-effects model in SAS assessed the effect of AI on decision time while accounting for scan difficulty. RESULTS:Without AI, correct BCC identification was 62% for Learner 1% and 64% for Learner 2 (combined 63%). With AI assistance, accuracy increased to 78% and 76%, respectively (combined 77%), reflecting relative improvements of 25% and 17% (combined +21%). Mean decision time decreased from 45 to 28 s for Learner 1 and from 35 to 22 s for Learner 2, yielding a combined reduction from 40 to 25 s (~38% faster). AI use significantly reduced decision time by an average of 15.1 s per image (p < 0.0001). AI standalone accuracy versus expert opinion was 64%, comparable to novice baseline performance. CONCLUSIONS:AI-enhanced OCT with VivoAID significantly improved novice users' diagnostic accuracy and efficiency, despite AI performance alone being similar to baseline novice interpretation. These data support VivoAID's role as a decision-support and potential educational tool in dermatology. Findings are limited by small sample size, single-institution design, and repeated review of the same scans. TRIAL REGISTRATION/BACKGROUND:None.

OBJECTIVE/UNASSIGNED:To study whether microfluidic sperm separation in intracytoplasmic sperm injection cycles provides any benefit over density gradient sperm separation for good-quality embryo formation. DESIGN/UNASSIGNED:Randomized sibling oocyte study. SUBJECTS/UNASSIGNED:Patients undergoing intracytoplasmic sperm injection. INTERVENTION/UNASSIGNED:Microfluidic sperm separation vs. density gradient sperm separation. MAIN OUTCOME MEASURES/UNASSIGNED:Primary outcomes were percentage of good-quality blastocyst formation. Secondary outcomes included sperm parameters after sperm separation, including percent motility, grade of forward progression, fertilization rates, blastocyst formation rates, and ploidy rates in the event that preimplantation testing for aneuploidy was performed. Additionally, subanalysis on those with male factor infertility was performed, evaluating primary and secondary outcomes above. RESULTS/UNASSIGNED:A total of 34 cycles enrolled into the study, yielding 456 oocytes, 231 randomized to microfluidics and 225 to density gradient (DG). Average microfluidic fertilization rate was 76.1% ± 19.2% and 72.4% ± 26.6% for DG. Microfluidic blastocyst formation rate was 58.4% ± 31.9% compared with 58.7% ± 30.5% for DG. Good-quality blastocyst formation rate for microfluidics was 51.4% ± 29.7% and for DG was 51.7% ± 30.9%. Euploid rates were 43.8% ± 35.5% in the microfluidics cohort and 33.7% ± 33.3% in the DG cohort. Subanalysis of cycles with male factor infertility revealed good-quality blastocyst formation rate was 45.9% ± 30.9% after microfluidics and 55.1% ± 29.2% for DG. Subanalysis of cycles with male factor infertility revealed an euploid rate of 50.0% ± 37.6% after microfluidics compared with 18.4% ± 24.5% for DG. CONCLUSION/UNASSIGNED:There were similar rates of good-quality embryo formation after intracytoplasmic sperm injection using sperm separated with microfluidics compared with density gradient; however, subanalysis of the male factor infertility group revealed higher euploid rates with microfluidics. TRIAL REGISTRATION/UNASSIGNED:This trial was registered in clinicaltrials.gov, ID number NCT04818593. URL: https://clinicaltrials.gov/study/NCT04818593. Date of registration: 3/25/2021. Date of first enrollment: 6/18/2021.

PURPOSE/OBJECTIVE:Uncertainty is inherent to clinical practice and impacts diagnostic reasoning, patient safety, and trust. Despite its ubiquity, health professions education has not adequately prepared learners to communicate uncertainty to patients, families, and care teams. Training remains variable and unevenly assessed. The authors examined how uncertainty communication is taught and assessed across the health professions and identified gaps to inform curricular development and scholarship. METHOD/METHODS:The authors conducted a scoping review guided by Arksey and O'Malley's framework and reported according to PRISMA-ScR guidelines. Eligible studies included learners from any health profession and addressed communication of uncertainty with patients and/or clinicians. Commentaries and reviews were excluded. Searches were conducted in PubMed, Ovid MEDLINE, Scopus, ERIC, CINAHL, and MedEdPORTAL beginning in March 2024 through August 2026. Data were analyzed using inductive and deductive analysis informed by Han's uncertainty taxonomy. Study quality was assessed using the Medical Education Research Study Quality Instrument (MERSQI). RESULTS:Searches identified 18,810 records. After screening, 213 full-text articles were reviewed and 21 were included in the final analysis. Most were conducted in the U.S. and published after 2019. Learners were predominantly physicians-in-training, with most studies focused on undergraduate and graduate medical education; fewer addressed continuing education or interprofessional learners. Diagnostic uncertainty was the most frequently addressed uncertainty type. Educational approaches were primarily experiential, including simulation, standardized patients, OSCEs, and role-playing. Fewer than half of studies involved patients in design, development, or assessment. Twenty studies assessed learners using self-reported surveys, faculty observations, or standardized patient evaluations. MERSQI scores ranged from 6.5 to 15.5 (mean 10.4). No study evaluated clinical practice or patient outcomes. CONCLUSIONS:Educational approaches to uncertainty communication are emerging but remain limited in scope, learner populations, and outcome evaluation. Future work should prioritize interprofessional, longitudinal curricula and rigorous assessment strategies linking education to clinical and patient-level outcomes.

In 2024, the International Anal Neoplasia Society (IANS) published the first consensus guidelines for anal cancer screening, outlining recommendations for patients who are most impacted by anal cancer. This study assesses provider knowledge and practice of these guidelines. A 37-item cross-sectional survey was distributed electronically to physicians, nurse practitioners, and physician assistants across ten specialties within a single health system. The survey assessed familiarity with anal cytology, guideline knowledge, screening practices, and barriers to screening. Descriptive statistics and bivariate analyses compared primary care providers (PCPs) to subspecialists. 87 providers completed the survey (62% physicians, 21% nurse practitioners, 17% physician assistants); 60% were Primary Care Physicians (PCPs) and 40% subspecialists. 55% had never heard of the IANS guidelines, and 76% had never performed an anal Pap test. Among the 70 providers completing the knowledge assessment, the median score was 10/20 (Inter Quartile Range (IQR) 8-12). Providers performed worst when identifying screening recommendations for solid organ transplant recipients (7% correct) and cisgender women with HIV (13% correct). No significant differences were found between PCPs and subspecialists across any measure. Qualitative responses identified scope of practice uncertainty (78%), lack of training (20%), and limited access to high-resolution anoscopy (9%) as primary barriers. Provider knowledge and utilization of anal cancer screening guidelines remain critically low across specialties. These findings highlight the urgent need for institution-wide education, standardized ordering pathways, and clear referral processes to improve screening rates.