Faculty Bibliography

Although previously B cells had been underestimated in comparison to T cells in their role in autoimmunity, now, their impact is well established. Via secretion of autoantibodies, presentation of autoantigens, regulation of antigen processing and presentation, and release of inflammatory cytokines, B cells can mediate cytotoxicity and lead to organ damage. B cell depletion via CD20 targeting effectively eliminates B cells in the blood and primary lymph organs and has found an effective role in the treatment of both rheumatological and neurological diseases. The neonatal Fc receptor (FcRn) is a key component of immune regulation that prevents IgG (produced by B cells) from degradation by lysosomes, sending it back into the extracellular compartment, thereby extending its half-life. This abundance of pathogenic IgG can lead to the development of autoimmune disease. The interplay between these two mechanisms of autoimmunity provides the great potential for combination therapy to reduce existent pathogenic IgG as well as prevent the production of new autoantibodies, though further investigation is needed to determine the risks, particularly of infection. This paper will explore existing B cell depleting treatments and FcRn inhibitors, and consider the potential impact for autoimmune disease as well as for the treatment of atherosclerosis.

Prostatic artery embolization (PAE) is a safe and effective minimally invasive treatment for lower urinary tract symptoms (LUTS) attributed to benign prostatic hyperplasia (BPH), including in patients with large prostates, who are poor surgical candidates or wish to avoid the morbidity of conventional surgery or transurethral interventions. As PAE becomes more widely adopted for BPH-related LUTS, objective measures of assessing treatment response are needed beyond symptom-based tools such as the International Prostate Symptom Score (IPSS) and Quality-of-Life (QoL) index. Imaging biomarkers complement these subjective endpoints by quantifying structural, functional, ischemic, and microstructural changes within the prostate before and after embolization. This review summarizes the principal imaging modalities used for biomarker assessment in PAE, with emphasis on ultrasound, magnetic resonance imaging (MRI), and computed tomography (CT) scans, and examines the current literature on imaging biomarkers of treatment response. Volumetric biomarkers, including whole prostate volume, central gland volume, and zonal volumetry index, provide quantitative assessment of gland reduction and may help predict clinical improvement, with zonal parameters showing stronger associations with symptomatic outcomes than whole-gland measurements alone. Functional biomarkers such as postvoid residual volume offer objective evaluation of bladder emptying alongside volumetric assessment, whereas ischemia-based biomarkers derived from contrast-enhanced MRI directly reflect embolization-induced devascularization. Diffusion-weighted imaging and apparent diffusion coefficient mapping provide additional information regarding post-embolization tissue remodeling, with b-value selection influencing early infarct detection. Emerging tools, including ultrasound elastography, radiomics, and artificial intelligence-assisted image analysis, may further refine patient selection, standardize response assessment, and improve predictive modeling, though prospective PAE-specific validation remains needed. Imaging biomarkers provide a more objective framework for evaluating PAE treatment response, with the potential to standardize outcome reporting, facilitate earlier identification of treatment success or failure, and guide biomarker-driven clinical decision-making. Prospective validation in larger PAE-specific cohorts remains essential before broader clinical adoption.

IMPORTANCE/UNASSIGNED:As transcatheter aortic valve replacement (TAVR) is considered for younger and lower-risk populations, the durability of bioprosthetic valves is increasingly important. Limited data exist on long-term (7 years and beyond) valve durability. OBJECTIVE/UNASSIGNED:To report 7-year valve durability outcomes for low-risk patients with symptomatic severe aortic stenosis treated with TAVR vs surgery. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:Between March 2016 and October 2017, a total of 1000 patients were enrolled at 71 centers in the US and Canada and randomized to undergo TAVR vs surgery. The patient population for the present analysis consisted of all patients who underwent valve implantation (495 with TAVR and 453 with surgery). The last 7-year follow-up occurred in March 2025. INTERVENTIONS/UNASSIGNED:Patients were randomized to balloon-expandable TAVR with the SAPIEN 3 valve or surgery with any commercially available valve. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The main outcomes of this analysis were stage 2 or 3 bioprosthetic valve dysfunction (BVD) related to structural valve deterioration (SVD), thrombosis, or endocarditis; all-cause bioprosthetic valve failure (BVF); BVF related to SVD; and aortic valve reintervention at 7 years. Analyses are presented as cumulative incidence rates with death as a competing risk. RESULTS/UNASSIGNED:The mean (SD) age of the study population was 73.5 (6.0) years, and 657 participants (69.3%) were male. Of 671 patients who were still alive and enrolled in the study at 7-year follow-up, 537 (80.0%) were available for echocardiographic analysis. Cumulative incidence rates of stage 2 or 3 SVD-related BVD (7.3% vs 7.6%; hazard ratio [HR], 0.96; 95% CI, 0.59-1.57; P = .88), all-cause BVF (6.9% vs 7.5%; HR, 0.91; 95% CI, 0.55-1.49; P = .69), SVD-related BVF (3.9% vs 5.3%; HR, 0.72; 95% CI, 0.39-1.36; P = .31), and valve reintervention (6.0% vs 5.5%; HR, 1.09; 95% CI, 0.62-1.90; P = .77) were low and similar for TAVR and surgery, respectively. Stage 2 or 3 thrombosis-related BVD (subclinical and clinical) occurred more frequently with TAVR (5.2% vs 0.9%; HR, 5.52; 95% CI, 1.92-15.85; P < .001), although most events occurred within 3 years and few progressed to BVF. Rates of stage 2 or 3 endocarditis-related BVD were also low and similar (0.4% in the TAVR group vs 0.5% in the surgery group; HR, 0.85; 95% CI, 0.12-6.07; P = .87). The proportion of patients alive and free of all-cause BVF was 73.4% (331/451) with TAVR vs 74.8% (288/385) with surgery (P = .69). CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this ad hoc analysis of a randomized clinical trial among low-risk patients with symptomatic severe aortic stenosis randomized to TAVR or surgery, both TAVR and surgery demonstrated comparable and sustained valve durability, with low and similar rates of SVD, all-cause BVF, and reintervention through 7 years. These findings may inform discussions of valve replacement strategies. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT02675114.

INTRODUCTION/UNASSIGNED:There is uncertainty about the benefits of cerclage in patients with transvaginal cervical length (TVCL) ≤10 mm and no prior spontaneous preterm birth. Our aim was to assess whether cervical cerclage in these patients was associated with prolonged pregnancy latency. METHODS/UNASSIGNED:This was an observational study of asymptomatic singleton pregnancies without a history of spontaneous preterm birth with extremely short cervix (TVCL ≤10 mm) in the second trimester. Exposure and outcome data were extracted manually from medical charts by obstetric providers, with all outcomes occurring prior to study initiation. All patients were prescribed vaginal progesterone and those with a cervical dilation >1.5 cm were excluded. The primary outcome was time interval from diagnosis to delivery (or 37 weeks' gestation, whichever occurred first). Secondary outcomes included gestational age at delivery, mode of delivery, and neonatal outcomes. We adjusted for parity and used log-binomial regression to estimate the relative risk for categorical variables and linear regression to estimate mean differences for continuous variables. RESULTS/UNASSIGNED:There were 247 patients with TVCL ≤10 mm during anatomy scan. After exclusions, 87 remained, of which 55 (63.2%) received cervical cerclage. At the time of diagnosis, the mean cervical length was 5.8 mm (cerclage group) versus 7.4mm (no cerclage group, difference: -1.6, 95% CI -0.6, -2.6) and the gestational age was 21.0 weeks (cerclage group) versus 22.1 weeks (no cerclage group, -1.1, 95% CI -1.8, -0.3). Mean pregnancy latency was longer in the cerclage group compared to the no cerclage group (13.4 vs 11.1 weeks, 2.2, 95% CI -0.3, 4.9), though there was a high level of uncertainty in the estimate. Term delivery occurred 30% more often in the cerclage group compared to the no cerclage group (RR 1.31, 95% CI 0.96, 1.79). CONCLUSION/UNASSIGNED:In our cohort, patients with extremely short cervix who received a cerclage had longer pregnancy latency than those who did not receive cerclage and more patients achieved term gestation, suggesting a potential benefit of cerclage in this population. However, given the high level of uncertainty of our estimates, additional research is needed to investigate these findings.

OBJECTIVES/OBJECTIVE:This study evaluates how access to abortion training influenced OBGYN residents who selected residency programs before and after the Dobbs decision. STUDY DESIGN/METHODS:Current OBGYN residents completed a survey in January 2024 as part of their annual in-training exam. Residents rated the importance of abortion training and compared access to abortion training to other factors (e.g., residency culture and happiness, geographic location) when selecting and ranking programs. We computed the percentage of residents reporting abortion training as important and a top factor when ranking programs. We used chi-squared test to compare differences between cohorts. RESULTS:Of the 6,134 residents surveyed, 3,182 consented to participation and had complete responses (52%). Overall, 2,281 (72%) considered abortion training important when choosing programs and 2,179 (69%) when ranking programs; 1,105 (71%) of post-Dobbs and 1,074 (66%) of pre-Dobbs residents considered abortion training important when ranking programs (p<0.01). Access to abortion training was a top three factor for 741 (23%) respondents when ranking programs. More post-Dobbs (392, 25%) than pre-Dobbs residents (349, 21%) considered access to abortion training as a top factor when ranking programs (p=0.01). CONCLUSIONS:Applicants weigh a variety of factors when selecting programs and may match to abortion restricted environments - this includes the 23% who considered abortion training a top factor. Future work should continue to focus on the impact of the Dobbs decision on residency program selection and the ability of all residents to develop abortion-care skills. IMPLICATIONS/CONCLUSIONS:Abortion training is an important consideration in residency program selection and essential for patient care. Without prioritization of abortion education, programs risk losing viable candidates and graduating residents without essential skills.

BACKGROUND AND STUDY AIMS/UNASSIGNED:Cholangiocarcinoma (CCa) is a complex malignancy of the biliary tract, classified as intrahepatic, perihilar, or distal. Digital single-operator cholangioscopy (D-SOC) enhances evaluation of biliary strictures, although it remains limited by suboptimal biopsy yield and technical constraints. Artificial intelligence (AI), particularly convolutional neural networks (CNNs), has emerged as a promising adjunct. However, performance across anatomical subtypes is not well defined. This study evaluated diagnostic performance of an AI-based model in detecting CCa lesions by location. PATIENTS AND METHODS/UNASSIGNED:A YOLOv8-based CNN was trained and validated using 315,993 D-SOC images from 183 patients across six international high-volume centers. Images were labeled as benign or malignant based on expert consensus. Frame-based analysis assessed diagnostic performance using macro-average F1-score, precision, and recall. Subgroup analysis explored anatomical site-specific performance. RESULTS/UNASSIGNED:Among the included patients (mean age 66.1±12.1 years; 64.5% male), 43.2% had perihilar, 37.2% intrahepatic, and 19.7% distal biliary strictures. The model demonstrated high overall performance: F1 score 95.3%, precision 95.5%, and recall 95.1%. Site-specific analysis revealed an F1 score of 89.6% for distal strictures and 91.1% for perihilar strictures. Receiver operating characteristic curves showed areas under the curve of 0.980 for intrahepatic strictures and 0.990 for perihilar and distal strictures. CONCLUSIONS/UNASSIGNED:This is the first study to demonstrate AI-based diagnostic performance across CCa topography using a large, multicenter D-SOC dataset. Although anatomical complexity affects detection, the model's high precision and generalizability suggest potential for clinical utility. These results support application of an AI-enhanced algorithm decision algorithm for cholangioscopy.

PURPOSE/OBJECTIVE:SET is a member of the inhibitor of histone acetyltransferases (INHAT) complex, involved in transcriptional silencing and gene regulation. Pathogenic variants in SET are postulated to cause neurodevelopmental disorder (NDD) phenotypes, but as only few individuals are described, detailed clinical information is scarce. Hence, currently counseling on phenotype and prognosis of this condition remains challenging. METHODS:Here we describe the clinical phenotype and mutational spectrum of 23 unreported individuals harboring (likely) pathogenic variants in SET. RESULTS:Phenotypes include global developmental delay with often pronounced hypotonia, delayed motor development and speech and language delay, ultimately evolving into (mild) intellectual disability. Comorbidities include behavioral concerns, sleeping disturbance and variable unspecific ocular problems. Next generation computer-assisted phenotyping using GestaltMatcher showed limited overlapping facial features between affected individuals and differences compared to disorders caused by related chromatin modifying genes. In addition, we generated a DNA methylation signature, able to distinguish individuals carrying pathogenic variants in SET from individuals with other NDDs and healthy controls. We used this DNA methylation signature to assess pathogenicity of two variants of uncertain significance in SET found in two additional individuals. CONCLUSION/CONCLUSIONS:Together, this expands the knowledge on the SET-related disorder and provides novel approaches for its diagnosis.

BACKGROUND:Transcatheter aortic valve replacement (TAVR) is an alternative to surgical aortic valve replacement for patients with symptomatic severe aortic stenosis. However, long-term outcomes data are lacking for TAVR, particularly with newer-generation transcatheter heart valves. OBJECTIVES/OBJECTIVE:The purpose of this study was to compare 10-year outcomes of intermediate-risk patients who underwent TAVR with the third-generation, balloon-expandable SAPIEN 3 valve in the PARTNER 2 SAPIEN 3 Intermediate-risk Registry (P2S3i) with those who underwent surgery in the PARTNER 2A (P2A) randomized trial. METHODS:Intermediate-risk patients were enrolled in the P2A trial from 2011 through 2013 and in the P2S3i registry in 2014. These prospective, multicenter studies used the same eligibility criteria and stratified patients based on suitability for transfemoral or transthoracic (transapical/transaortic) access. Ten-year outcomes were evaluated, including all-cause mortality, aortic valve reintervention, and core laboratory-adjudicated echocardiographic outcomes. Patient reconsent was required at 5 years for extended 10-year follow-up, and vital status sweeps were implemented to improve data completeness for all-cause mortality. To account for potential baseline differences and reduce confounding, P2S3i TAVR patients were propensity score-matched 1:1 to P2A surgical patients. RESULTS:Among 2,005 patients who received a valve, 1,069 underwent TAVR in P2S3i and 936 underwent surgery in P2A. After propensity score matching (N = 783 patients in each group), baseline characteristics were similar between groups: mean age was approximately 82 years, 43% were female, and mean Society of Thoracic Surgeons score was 5.5%. At 10 years, all-cause mortality rate was 83.4% after TAVR and 82.3% after surgery, respectively (HR: 1.01 [95% CI: 0.91-1.13]; P = 0.82). Aortic valve reintervention rates adjusted for competing mortality were 2.0% for TAVR and 1.9% for surgery (P = 0.47). Among 32 TAVR and 30 surgical patients with available echocardiographic data at 10 years, mean gradients were 11.0 mm Hg and 12.6 mm Hg, respectively. CONCLUSIONS:At 10 years, TAVR with the SAPIEN 3 valve and surgery resulted in similar rates of mortality and aortic valve reintervention, and similar hemodynamics in intermediate-risk patients with symptomatic severe aortic stenosis. This analysis highlights challenges associated with extended long-term follow-up of clinical trials, including differential loss to follow-up and the competing risk of mortality in elderly populations. (PARTNER 2A Trial; NCT01314313; PARTNER 2 SAPIEN 3 Intermediate-Risk Registry; NCT03222128).