Washington University School of Medicine (WUSM) is the medical school of Washington University in St. Louis in St. Louis, Missouri. Founded in 1891, the School of Medicine has 1,260 students, 604 of which are pursuing a medical degree with or without a combined Doctor of Philosophy or other advanced degree. It also offers doctorate degrees in biomedical research through the Division of Biology and Biological Sciences. The School has developed large physical therapy (273 students) and occupational therapy (233 students) programs, as well as the Program in Audiology and Communication Sciences (100 students) which includes a Doctor of Audiology (Au.D.) degree and a Master of Science in Deaf Education (M.S.D.E.) degree. There are 1,772 faculty, 1,022 residents, and 765 fellows.The clinical service is provided by Washington University Physicians, a comprehensive medical and surgical practice providing treatment in more than 75 medical specialties. Washington University Physicians are the medical staffs of the two teaching hospitals – Barnes-Jewish Hospital and St. Louis Children's Hospital. They also provide inpatient and outpatient care at the St. Louis Veteran's Administration Hospital, hospitals in the BJC HealthCare system and 35 other office locations throughout the greater St Louis region. U.S. News and World Report ranks the college high; the school is currently ranked 6th for research and has been ranked as high as 2nd in 2003 and 2004, It has been listed among the top ten medical schools since rankings were first published in 1987. The school ranks first in the nation in student selectivity. As of 2019, it also receives the third most funding among all medical schools in the US from the National Institue of Health, totalling an amount of $218 million. Globally, the school is ranked as the 20th and 35th best medical program in 2020 by the Times Higher Education’s World University Rankings for medicine and QS World University Ranking for medicine, respectively.
Background: Substance use disorders (SUDs) are moderately to highly heritable and develop in stages that typically begin in adolescence or young adulthood. The predominant use of cross-sectional adult samples to study SUDs and their genetic liability leaves it unclear whether their correlates may plausibly reflect predispositional risk and/or arise as a consequence of exposure. Methods: We conducted a phenome-wide association study (PheWAS) of polygenic scores (PGSs) for SUDs (i.e., problematic alcohol use, tobacco use disorder, cannabis use disorder [CUD], opioid use disorder [OUD], and a general addiction risk factor) in children ages 8 to 13 years ( n European ancestry = 5556; n African American ancestry = 1584) enrolled in the Adolescent Brain Cognitive Development (ABCD) Study. Up to 1697 phenotypes were examined across several domains, including mental health, substance use, physical health, cognition, and screen media. Results: The PheWAS yielded 309 significant associations with the SUD PGS, particularly among mental health, sleep, screen time, and caffeine consumption phenotypes. Most associations remained significant in substance-naïve participants. The CUD PGS had the largest number of associations and was particularly associated with externalizing behavior in both genetic ancestry subsamples. OUD PGS associations were enriched for cognitive and neighborhood environmental phenotypes. Neuroimaging phenotypes (e.g., resting-state functional connectivity) partially accounted for associations between the SUD PGS and screen time phenotypes. Conclusions: Genetic liability to SUDs is expressed during childhood as potentially modifiable risk factors that could be targeted to attenuate its expression in adolescence and adulthood.
Purpose Type 2 diabetes mellitus is a risk factor for compressive neuropathy. The purpose of this study was to determine whether metformin use is associated with reduced rates of compressive neuropathy, primary nerve decompression surgery, and revision after carpal tunnel release and cubital tunnel release, while controlling for concurrent diabetes medications. Methods We performed a retrospective cohort study using the TriNetX federated research network. Adults with type 2 diabetes mellitus were stratified by metformin exposure, defined as at least 10 prescriptions over 5 years. The primary outcomes were incident compressive neuropathy and nerve decompression surgery. In a unilateral revision cohort, the outcome was ipsilateral revision between 30 days and 5 years after the index procedure. One-to-one propensity score matching balanced cohorts on demographics, comorbidities, and concurrent diabetes medications. Four prespecified medication-stratified sensitivity analyses addressed insulin, sodium-glucose cotransporter-2 inhibitors, and glucagon-like peptide-1 receptor agonists. Carpal tunnel release and cubital tunnel release revision results were pooled via fixed-effect meta-analysis. Results After matching, the primary analysis included 260,823 pairs. Metformin users had lower rates of nerve decompression surgery (0.60% vs 0.72%; odds ratio, OR, 0.831 [0.776–0.889]) and compressive neuropathy diagnosis (2.78% vs 3.05%; OR, 0.909 [0.879–0.941]). The surgery-level association was stronger without concurrent insulin (OR, 0.727 [0.662–0.799]) and attenuated to nonsignificance with concurrent insulin (OR, 0.948 [0.836–1.076]), though the diagnosis-level association persisted. Among patients with unilateral carpal or cubital tunnel syndrome, ipsilateral revision was less frequent in metformin users (pooled OR, 0.711 [0.533–0.950]). Metformin users also had lower vitamin B12 levels (mean, 646.4 vs 707.4 pg/mL), consistent with sustained metformin exposure. Conclusions Metformin use was associated with reduced incidence of nerve decompression surgery and ipsilateral revision after carpal tunnel release and cubital tunnel release in patients with type 2 diabetes mellitus, with directionally consistent effects across sensitivity analyses. These findings suggest that maintaining metformin therapy may carry benefit beyond glycemic control. Prospective studies are needed to validate these findings. Type of study/level of evidence Prognostic II.
Medullary thyroid cancer (MTC) is a rare neuroendocrine malignancy arising from parafollicular C cells. Diagnosis is based on cytologic and histologic features, supported by biochemical testing for calcitonin and carcinoembryonic antigen, RET germline testing, and appropriate imaging. This educational review, developed by the Society of Surgical Oncology's Endocrine and Head and Neck Disease Site Working Group, provides an updated overview of the diagnosis and management of MTC, emphasizing evolving surgical principles and the integration of targeted therapies. Ongoing multidisciplinary collaboration and participation in clinical trials remain essential to further refine prognostic tools, optimize treatment sequencing, and improve patient outcomes in MTC.
BACKGROUND:Plasma biomarkers, such as neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), phosphorylated tau (pTau217), and total tau (tTau), are associated with cognitive decline. However, the role of sleep quality in modifying these associations remains unclear. This study examines whether subjective sleep quality, as measured by the Pittsburgh Sleep Quality Index (PSQI), modifies the associations between plasma biomarkers and cognitive performance. METHODS:We analyzed cross-sectional data from 491 adults aged 36 years or older in the Aging Adult Brain Connectome study. Plasma levels of NfL, GFAP, pTau217, and total tTau were measured. Cognitive performance was assessed using the Montreal Cognitive Assessment (MoCA) and the Preclinical Alzheimer's Cognitive Composite (PACC). Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI). Generalized linear models were used to test main and moderation effects while adjusting for demographics. Sensitivity analyses included APOE ε4 status and body mass index. RESULTS:Higher plasma levels of NfL, GFAP, and pTau217 were associated with lower cognitive performance on both MoCA and PACC (all p < .05). Poorer sleep quality was independently associated with worse PACC outcomes. Critically, significant moderation effects were observed: PSQI moderated the negative associations between GFAP and MoCA (β = 0.0020, p = .009) and between pTau217 and MoCA (β = 0.0299, p = .003), indicating a synergistic relationship between sleep quality and glial/amyloid-related pathology in cognitive aging. CONCLUSION:Sleep quality modifies biomarker-cognition associations, highlighting its potential as a behavioral target to support brain health.
Importance:Early-onset colorectal cancer (EOCRC) (diagnosed age <50 years) incidence is increasing globally, in parallel with increased consumption of ultraprocessed foods (UPFs). The role of UPFs in early-onset colorectal neoplasia remains underexplored. Objective:To evaluate the association between UPF consumption and risk of EOCRC precursors. Design, Setting, and Participants:This prospective cohort study included participants of the Nurses' Health Study II, an ongoing US prospective cohort of female registered nurses established in 1989. Participants were followed up from June 1, 1991, through June 1, 2015. Data were analyzed from October 2024 to July 2025. UPF intake, derived from food-frequency questionnaires administered every 4 years and classified using the Nova system, was modeled as quintiles of energy-adjusted servings per day. Of the nurses enrolled, those who had completed the baseline 1991 food-frequency questionnaire, undergone at least 1 lower endoscopy before age 50 years after baseline, had no history of cancer (except for nonmelanoma skin cancer) before endoscopy, and no colorectal polyp or inflammatory bowel disease were included. Main Outcomes and Measures:Incidence of EOCRC precursors, including conventional adenomas and serrated lesions, confirmed via medical records and pathology reports. Multivariable logistic regression models with generalized estimating equations for clustered data were used to estimate adjusted odds ratios (AORs) and 95% CIs, accounting for known and putative risk factors. Results:Among 29 105 female participants (mean [SD] age, 45.2 [4.5] years) over 24 years of follow-up, 1189 cases were documented of early-onset conventional adenomas and 1598 serrated lesions. UPFs provided 34.8% of total daily calories (median, 5.7 [IQR, 4.5-7.4] servings per day). Participants with higher UPF intake had an increased risk of early-onset conventional adenomas (highest vs lowest intake: AOR, 1.45; 95% CI, 1.19-1.77; overall P < .001) but not serrated lesions (AOR, 1.04; 95% CI, 0.89-1.22; P = .48 for trend). Findings were consistent after further adjustment for body mass index, type 2 diabetes, dietary factors (fiber, folate, calcium, and vitamin D), and Alternative Healthy Eating Index-2010 score. Conclusions and Relevance:In this study, higher UPF intake was associated with increased risk of early-onset colorectal conventional adenomas. These data highlight the important role of UPFs in early-onset colorectal tumorigenesis and support improving dietary quality as a strategy to mitigate the increasing burden of EOCRC.
