Faculty Bibliography

In patients with coronary artery disease (CAD), aspirin has long represented the cornerstone of antiplatelet therapy for secondary prevention. In patients with an acute coronary syndrome (ACS) and undergoing percutaneous coronary intervention (PCI), oral P2Y₁₂ inhibitors have traditionally been used as adjuncts to aspirin, a strategy known as dual antiplatelet therapy (DAPT). Although DAPT reduces the risk of ischemic recurrences, it carries a risk of bleeding. In CAD patients with a concomitant indication for oral anticoagulation (OAC)-who account for approximately 15% of patients--the combination of aspirin and OAC is associated with an increased risk of bleeding without ischemic benefit. The adverse impact of bleeding on prognosis has prompted investigations aimed at identifying antithrombotic treatment regimens associated with reduced bleeding without compromised ischemic protection. Among these, a strategy of aspirin withdrawal after a brief period of combination therapy has emerged as an attractive option. The efficacy and safety of aspirin withdrawal, however, vary substantially according to clinical setting, patient profile (eg, age, sex, ethnicity, genetic background, and comorbidities), timing of discontinuation after ACS or PCI, and alternative adjunctive antithrombotic therapy, including use of OAC and choice of P2Y₁₂ inhibitor. After reviewing the pharmacologic rationale for aspirin withdrawal, the clinical trial evidence, and guideline recommendations, we provide practical considerations for the implementation of this strategy in patients with CAD, with and without an indication to be on OAC.

PURPOSE OF REVIEW/OBJECTIVE:Diabetes care is characterized by the widespread use of plastics. With plastic-associated endocrine-disrupting chemicals (EDCs) implicated in diabetes pathogenesis, this review examines how medical plastics relate to diabetes and related disorders and proposes interventions to improve the situation. RECENT FINDINGS/RESULTS:Plastic-associated EDCs and micro-/nanoplastics (MNPs) are linked to metabolic dysfunction. Medical care exposes patients to these agents; however, the precise contribution of diabetes care to these exposures and their associated adverse health effects remains poorly defined. Diabetes care is an increasingly important contributor to plastic pollution and climate change, yet inadequate systems exist to mitigate its environmental impact. Plastic-associated EDCs and MNPs remain an underappreciated metabolic health threat. Mitigating the deleterious impacts of plastics on human and planetary health requires concerted actions from manufacturers, scientists, policymakers, professional organizations, healthcare providers, and patients. Doing so has the potential to improve metabolic health and promote health equity.

Acromioclavicular joint injury reconstructive options include a wide number of described techniques. Although no single technique has consistently demonstrated superior clinical outcomes in the literature, there are theoretical biomechanical benefits to a combined reconstructive technique using cortical suture button and semitendinosus allograft. This review describes an acromioclavicular joint reconstruction using a cortical suture button and semitendinosus allograft.

BACKGROUND AND AIMS/OBJECTIVE:Non-selective beta-blockers (NSBB) are widely used to prevent decompensation in cirrhosis. Guidelines recommend discontinuing NSBB in patients with cirrhosis and acute kidney injury (AKI), although based largely on expert opinion and limited evidence. We evaluated the impact of NSBB on AKI outcomes in patients with cirrhosis. METHODS:This multicenter study enrolled patients hospitalized for decompensated cirrhosis and AKI. Data on NSBB treatment, type and dose and continuation/discontinuation/tapering were collected. Outcomes were compared between patients receiving and not receiving NSBB and between those who discontinued/tapered and those who did not. Inverse probability of treatment weighting (IPTW) balanced demographics, liver disease severity, hemodynamic parameters, AKI stage and acute-on-chronic liver failure (ACLF) grade. Main outcomes were AKI resolution and 28-day mortality. RESULTS:Out of 1,238 patients with AKI, 503 were on NSBB (propranolol 55%; carvedilol 45%). After IPTW adjustment, NSBB treatment at AKI diagnosis was associated with higher likelihood of AKI resolution (sHR=1.29 [95% CI=1.12-1.48], p<0.001) and reduced 28-day mortality (sHR=0.70 [95% CI=0.55-0.91], p=0.006). At 48-72 hours from AKI diagnosis, NSBB were continued in 122 patients (24%) and discontinued/tapered in 349 (69%); 4 patients died, and data were not available for the remaining 28 patients. After excluding patients in whom NSBB continuation was not clinically feasible (n=59), IPTW-adjusted analysis showed no evidence of an association between NSBB continuation and AKI resolution (sHR=0.84 [95% CI=0.57-1.25], p=0.391) or 28-day mortality (sHR=0.51 [95% CI=0.23-1.11], p=0.089). CONCLUSION/CONCLUSIONS:NSBB use at AKI diagnosis was associated with improved renal recovery and survival in patients with acutely decompensated cirrhosis and AKI. Continuation during hospitalization does not appear harmful, supporting careful individualized management rather than systematic withdrawal. IMPACT AND IMPLICATIONS/UNASSIGNED:Owing to potential adverse hemodynamic effects, current guidelines recommend discontinuation of non-selective beta-blockers (NSBB) in patients with Acute Decompensation (AD) of liver cirrhosis and Acute Kidney Injury (AKI). However, this recommendation relies largely on expert opinion, since robust clinical evidence is lacking. This study prospectively evaluated the impact of NSBB on AKI outcomes in a large multicentre cohort of patients with AD and AKI. Treatment with NSBB at AKI diagnosis was associated with greater likelihood of AKI resolution and lower risk of 28-day mortality, while no evidence of an association between early discontinuation and improved outcomes was observed. These findings support a personalized approach to NSBB management in decompensated patients with AKI and highlight the need to identify patients who may benefit most from NSBB discontinuation.

BACKGROUND:In the U.S., about one million people with active epilepsy are adults aged 55+. Older adults with epilepsy (OAWE) experience complex health conditions that compromise quality of life (QOL). The contribution of depressive symptom dimensions to health-related QOL remains underexplored in OAWE. METHODS:We analyzed baseline data from 13 epilepsy self-management studies in the CDC-sponsored MEW-DB (Managing Epilepsy Well Database), including adults ages 55 and older (N = 198). The primary outcome was health-related QOL, assessed via the 10-item Quality of Life in Epilepsy scale (QOLIE-10), which was inverse rank normalized (mean = 0, SD = 1). Primary predictors included the Patient Health Questionnaire (PHQ-9) total score, cognitive and somatic symptom sub scores, and suicide ideation. Multivariable mixed-effects linear regression was used to assess associations. Models included a random intercept for originating study. RESULTS:) were associated with worse QOLIE-10 total scores when adjusting for likely confounders. Suicide ideation was not associated with QOLIE-10 (β = 0.07 SD, 95% CI: -0.15 to 0.29, p = 0.51). Past 30-day seizure occurrence was associated with worse total QOLIE-10 only when depressive terms were excluded from the multivariable model (β = 0.38 SD, 95% CI: 0.05-0.72, p = 0.024). CONCLUSIONS:Among OAWE, depressive symptoms are strongly linked to reduced QOL. These findings underscore the importance of integrated mental health screening and intervention for OAWE.

This article synthesizes findings from the Reengineering Health Decision-Making Environments: Aligning Research, Policy, and Innovation for Societal Benefit symposium. Health decisions by patients and providers are often suboptimal, not because effective knowledge or tools are unavailable, but because the conditions under which decisions are made do not support their best use. The symposium brought together researchers, practitioners, and policy makers to examine how health decision-making environments could be reengineered to improve decisions across the care continuum. Three complementary levers emerged as especially promising: behavioral science principles, learning health systems, and artificial intelligence. Achieving these gains at scale will require sustained investment in embedded testing infrastructure, payment and regulatory models that support delivery innovation, and equity-centered design from the outset.

Squamous cell carcinomas (SCCs) are common epithelial malignancies frequently associated with EZH2 upregulation, which correlates with aggressive growth and poor prognosis. EZH2 functions as the catalytic subunit of Polycomb repressive complex 2 (PRC2), which deposits the repressive H3K27me3 histone mark, yet PRC2 function in SCC pathogenesis remains unresolved. Here, we uncover a paradox: although EZH2 is elevated, the PRC2-catalyzed H3K27me3 is profoundly reduced in human SCC and complementary murine models. Mechanistically, we identify that oncogenic Ras signaling causes degradation of the PRC2 subunit EED, destabilizing PRC2 and depleting H3K27me3. Loss of EED reprograms keratinocytes into an aggressive tumor-specific cell state and induces paracrine factors that remodel the tumor microenvironment, driving metastasis. Remarkably, reintroducing EED suppresses tumor growth via restoring PRC2 integrity and H3K27me3 levels, revealing the reversibility of this epigenetic collapse. These findings link oncogenic signaling to epigenetic reprogramming and uncover PRC2 reconstitution as a potential therapeutic option in epithelial cancers.

BACKGROUND/UNASSIGNED:Vascularized composite allotransplantation (VCA) restores form and function in patients with severe disfigurement, yet acute rejection remains common within the first year. In solid organ transplantation, rituximab, a B cell-depleting agent, has been shown to reduce rejection in highly sensitized recipients, and donor-specific antibodies (DSAs) are established biomarkers of rejection. The impact of rituximab and DSAs in VCA remains unclear. This study examined rejection-free survival following rituximab induction and the relationship between positive DSA levels and rejection in VCA recipients. METHODS/UNASSIGNED:This retrospective review analyzed 4 patients who underwent facial transplantation between 2015 and 2023 at our institution. All patients received rituximab and antithymocyte globulin as part of their induction immunosuppression. Rejection-free survival was the primary outcome, with DSA levels assessed at baseline and throughout follow-up. A generalized linear mixed-effects model was used to evaluate the relationship between DSA positivity and rejection. RESULTS/UNASSIGNED:= 0.693). Some patients were DSA-negative during clinical rejection, and some were DSA-positive without signs of rejection. CONCLUSIONS/UNASSIGNED:This is the first study to evaluate rituximab-based induction in a cohort of VCA recipients, demonstrating median rejection-free survival exceeding one and a half years. Although some patients were DSA-positive during rejection episodes, no significant correlation was observed, challenging the predictive value of DSAs as seen in solid organ transplantation and highlighting the need to explore alternative biomarkers for rejection in VCA.