Faculty Bibliography

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.

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.

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.

INTRODUCTION/BACKGROUND:Immune checkpoint inhibitors (ICI) have transformed the treatment landscape for triple-negative breast cancer (TNBC), but their efficacy in older adults remains unclear. The objective of this systematic review is to evaluate the efficacy of ICI in patients with TNBC aged ≥65 years. MATERIALS AND METHODS/METHODS:We conducted a systematic review of randomized controlled trials (RCTs) between January 2013 and September 2023 using searches of Medline, Embase, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform. RESULTS:Eighteen full-text articles representing 11 unique RCTs were identified. Only four RCTs reported efficacy outcomes for patients ≥65 years: KEYNOTE 355, KEYNOTE 522, IMpassion130, and IMpassion131. Across these trials, 602 of 3215 patients (18.7%) were 65 and older. The overall risk of bias was low to intermediate, but heterogeneity in trial design and endpoints precluded meta-analysis. Pembrolizumab, the only FDA-approved ICI in TNBC, showed a nonsignificant trend toward improved pathological complete response and event-free survival among older adults with early-stage TNBC (KEYNOTE-522). In the metastatic setting, pembrolizumab may improve overall survival in older patients with PD-L1 combined positive score ≥ 10 (KEYNOTE-355). All studies enrolled few older patients, and none prespecified age-stratified analyses. DISCUSSION/CONCLUSIONS:These findings highlight a major evidence gap and underscore the need for further research evaluating ICI outcomes in older adults with TNBC.

Repetitive head impacts sustained during American football have been associated with neuropathological changes such as white matter shear injuries. However, the impact of specific factors, such as age of first exposure and cumulative head impact burden, on white matter integrity remains unclear. This study investigated in vivo white matter microstructural changes using diffusion tensor imaging and tract-based spatial statistics in 165 male former American football players (mean age 57.3 years, range 45-74) and 52 unexposed asymptomatic male controls (mean age 59.4 years, range 45-74) in the DIAGNOSE CTE Research Project. Compared to controls, former football players exhibited significantly higher fractional anisotropy (FA) in 1.97% of the white matter skeleton (1552 voxels; Cohen's d = 0.587) and higher tissue-corrected FA (FAt) in 1.48% of the white matter skeleton (1004 voxels; Cohen's d = 0.616). No significant differences were observed for mean diffusivity, axial diffusivity, radial diffusivity, or free water between football players and controls. Among football players, there were no significant differences in the white matter microstructure between players diagnosed with traumatic encephalopathy syndrome and those without the diagnosis. Lower FA was significantly associated with older age (P < 0.00001) and an earlier age of first exposure to tackle football (P < 0.01), while lower FAt was associated with greater cumulative head impact burden, specifically higher linear acceleration (P < 0.04) and rotational force (P < 0.02). This study highlights the influential role of exposure factors on white matter microstructure in former American football players, as well as the utility of diffusion tensor imaging to aid in characterizing the long-term effects of repetitive head impacts in contact sport athletes.

The American Society for Gastrointestinal Endoscopy (ASGE) Technology Committee provides reviews of existing, new, or emerging endoscopic technologies that have an impact on the practice of GI endoscopy. Evidence-based methodology is used, with a MEDLINE literature search to identify pertinent clinical studies on the topic and a MAUDE (U.S. Food and Drug Administration Center for Devices and Radiological Health) database search to identify the reported adverse events of a given technology. Both are supplemented by accessing the "related articles" feature of PubMed and by scrutinizing pertinent references cited by the identified studies. Controlled clinical trials are emphasized, but in many cases, data from randomized, controlled trials are lacking. In such cases, large case series, preliminary clinical studies, and expert opinions are used. Technical data are gathered from traditional and Web-based publications, proprietary publications, and informal communications with pertinent vendors. Technology Status Evaluation Reports are drafted by 1 or 2 members of the ASGE Technology Committee, reviewed and edited by the committee as a whole, and approved by the Governing Board of the ASGE. When financial guidance is indicated, the most recent coding data and list prices at the time of publication are provided. For this review, the MEDLINE database was searched through August 2024 for articles related to endoscopic submucosal dissection. Technology Status Evaluation Reports are scientific reviews provided solely for educational and informational purposes. Technology Status Evaluation Reports are not rules and should not be construed as establishing a legal standard of care or as encouraging, advocating, requiring, or discouraging any particular treatment or payment for such treatment.

Papillary renal neoplasm with reverse polarity (PRNRP) has been proposed as a distinct subtype of renal cell neoplasm with recurrent KRAS mutations and indolent behavior. However, its epigenetic landscape is poorly understood. In this study, 12 PRNRPs and a PRNRP initially diagnosed as "papillary adenoma" were analyzed. All 13 cases underwent targeted next-generation sequencing for driver mutations. Eleven PRNRPs were profiled using the Illumina MethylationEPIC array and compared with a reference cohort of 71 common renal cell tumors. KRAS mutations were identified in 12 of 13 (92%) cases of PRNRP. Copy-number analysis from methylation profiling showed that 9 of 11 (82%) PRNRPs lacked copy-number changes. Two cases showed a focal loss of chromosome 8 and a gain of chromosome 16, respectively. Unsupervised clustering based on methylation data showed that PRNRPs form a distinct epigenetic group, separate from papillary renal cell carcinomas (pRCCs) and other major renal tumors, but with the closest affinity to clear cell papillary renal cell tumors. In addition, DNA methylation analysis suggested PRNRP may arise from the distal nephron, in contrast to pRCC, which appears to recapitulate proximal tubules. These findings support PRNRP as a subtype of renal cell neoplasm with a distinct epigenetic signature.

The Yazidi community endured an unprecedented genocide by the Islamic State (ISIS) in August 2014, resulting in mass killings, kinocide, abductions, ongoing disappearances, and sexual enslavement. The intense trauma led to high prevalence rates of posttraumatic stress disorder (PTSD), depression, anxiety, and profound sleep disturbances. This comprehensive article integrates epidemiological data, neurobiological mechanisms, and clinical case reports to elucidate sleep disorders among Yazidi survivors. We detail the historical context, transgenerational trauma, specific sleep-related pathologies (insomnia, nightmares, parasomnias, and disrupted circadian rhythms), neurobiological underpinnings, cultural factors, and evidence-based interventions (e.g., Narrative Exposure Therapy (NET); Cognitive Behavioral Therapy for Insomnia (CBT-I)). Furthermore, we discuss the establishment and role of the Institute for Psychotherapy and Psychotraumatology (IPP) at the University of Duhok, outline barriers to care, and propose future research directions and policy recommendations.

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).