Albert Einstein College of Medicine

Peripheral artery diseases (PADs) are a growing public health problem globally and a common, debilitating comorbidity among dialysis patients. However, the impact of social determinants of health on PAD within this population remains underexplored. This study evaluated associations between zip code-level socioeconomic indicators and PAD incidence and prevalence among US dialysis patients. The 2022 Medicare Dialysis Facilities dataset was used to identify US dialysis centers and matched associated zip codes with the Centers for Disease Control and Prevention and Agency for Toxic Substance and Disease Registry Social Vulnerability Index. Variables included community-level indicators of income, housing, employment, insurance, and access to care. Multivariable linear regression models were constructed in SPSS between social determinants of health and PAD burden. PAD incidence and prevalence were highest in the Northeast (M = 9.11, M = 18.66 respectively). Incidence was positively associated with poverty (β = 0.200, P < 0.001) and uninsurance (β = 0.052, P = 0.015), whereas housing burden, unemployment, education, and region showed inverse associations. For PAD prevalence, uninsurance remained positively associated (β = 0.088, P < 0.001); poverty, rurality, and region were negative predictors. Interaction terms (uninsurance × region; uninsurance × rurality) were significant for both outcomes. Model fit was modest (adjusted R2 = 0.018-0.031). Uninsured status and poverty are key SDHs linked to PAD in dialysis patients, although effects vary by incidence and prevalence, reflecting the combined influence of structural, geographical, and facility disparities.

To investigate longitudinal trends in the American Board of Emergency Medicine (ABEM) Qualifying Examination (QE) performance, identify statistically significant inflection points in pass rates, and determine factors associated with the recent decline observed in 2022. This was a retrospective, observational study conducted in 2 phases. Phase 1 analyzed all QE attempts from 1980 to 2024 (n = 83,254) to identify changepoints using segmented regression and Bayes factor comparisons. Phase 2 focused on QE attempts surrounding the most recent changepoint from 2016 to 2024 (n = 23,784) and used multilevel nonlinear piecewise growth models to examine the association between physician characteristics and QE pass rates before and after the 2022 changepoint. Three statistically significant changepoints were identified: 1988, 2003, and 2022. Although increases in pass rates were noted in 1988 and 2003, 2022 was marked by a decline in pass rates with a steeper drop post-2022 (slope from 2016 to 2022 = -0.17 vs slope 2022 to 2024 = -0.67). From 2016 to 2022, MD graduates had a lesser decline in performance compared with non-MD peers. After 2022, those trained during the COVID pandemic also experienced a lesser decline. ABEM QE pass rates experienced 3 major inflection points since 1980, with the most recent occurring in 2022 and representing a meaningful decline. Physician-level characteristics, particularly medical school degree type and COVID-era training, were significantly associated with this trend.

Colorectal cancer (CRC) is the second-leading cause of cancer-related deaths. Mutations in the tumor-suppressor APC initiate CRC in part by preventing the glycogen synthase kinase 3 (GSK3) kinase from phosphorylating β-CATENIN, leading to its stabilization and transactivation of mitogenic target genes. While the importance of β-CATENIN phosphorylation by GSK3 is well established, APC regulation of GSK3 activity upon other targets is not understood. Here, we identify the H4K20 methyltransferase SETD8 as a target of APC-coordinated GSK3 phosphorylation in the intestinal epithelium. We find that phosphorylation by GSK3 restrains the oncogenic activity of SETD8, with loss of phosphorylation sensitizing mice to oncogenic insults. Mechanistically, loss of SETD8 phosphorylation in tumors results in a loss of H4K20 monomethylation (H4K20me1) deposition at oncogenic cholesterol biosynthesis and fetal intestinal genes, allowing for their activation in part through gain of YAP accessibility. These results underscore the importance of SETD8 in CRC and represent a novel β-CATENIN-independent oncogenic consequence of APC loss.

Pharmacological options for treating arrhythmic mitral valve prolapse (aMVP) are limited and anecdotal. Ranolazine as an antiarrhythmic has yielded satisfactory outcomes in suppressing ventricular arrhythmias, but its role in the case of aMVP is unknown. A 62-year-old female presented complaining of palpitations. ECG and the cardiac monitor showed very frequent and complex monomorphic premature ventricular contractions (PVCs), likely from the posteromedial papillary muscle. Cardiac MRI revealed the presence of mitral valve prolapse. Empirical treatment with ranolazine 1000 mg b.i.d. was initiated for antiarrhythmic purposes, with subjective clinical improvement and objective reduction of complex PVCs after 32 months of follow-up. Papillary muscle PVCs are a common finding in patients with aMVP. Antiarrhythmic properties of ranolazine can be safely used in patients with contraindications to other interventions for the treatment of PVCs associated with mitral valve prolapse. The effect seems more evident on complex PVCs and ventricular tachycardia and can be attributed to an intrinsic use dependence of the drug; therefore, this treatment should be explored for selected cases. To the best of our knowledge, this is the first report of a case of improvement in PVCs following the administration of a high dose of ranolazine in a patient with aMVP. Future investigations on a larger scale should focus on whether ranolazine can be safely used as an alternative treatment to reduce the risks of ventricular arrhythmia and improve patients' prognosis.

Postoperative hematoma is a common yet unfavorable complication following head and neck free flap reconstruction (HNFFR). This study aims to clarify how perioperative blood pressures influence postoperative neck hematoma development and its effect on outcomes in patients undergoing HNFFR.A retrospective chart review was conducted for all patients who underwent HNFFR at a single academic institution between January 2020 and December 2023. Data included demographics, radiation history, comorbidities, flap type, complications, and blood pressures at preoperative, intraoperative, early (<24 hours), and late (days 1-7) postoperative periods.A total of 317 patients with 329 flaps were included in our analysis. Twenty-seven patients developed a neck hematoma, and flap failure was significantly higher in these patients (11.1% vs. 2.4%, p = 0.044). After adjusting for potential confounding variables, hematoma formation was significantly associated with higher preoperative systolic and pulse pressures; peak early postoperative systolic pressures; and peak late postoperative systolic, diastolic, and mean arterial pressures (MAP). In a multivariate model including preoperative, early, and late postoperative MAP, only late postoperative MAP remained an independent predictor of hematoma. Each 1 mm Hg rise in late MAP raised hematoma odds by 4% (OR: 1.04, p = 0.004), and receiver operator curve analysis identified late MAP ≥ 117.8 carried a fivefold higher risk of hematoma (OR: 5.24, p < 0.001).Our findings suggest that postoperative blood pressure control is critical in reducing hematoma risk following HNFFR. Strict postoperative blood pressure management, particularly maintaining a MAP goal of < 110 mm Hg, may reduce hematoma risk and associated flap failure.