Johnson University

Epidermolysis bullosa acquisita (EBA) is a rare, acquired autoimmune blistering disease developing due to autoantibodies against collagen VII (COL7), a protein crucial to maintaining skin integrity [1]. While the exact cause of EBA is unknown, medications and vaccines have been described as triggers in limited studies [2]. In this study, we utilize various pharmacovigilance databases, including the United States Food and Drug Administration Adverse Event Reporting System (FAERS), Vaccine Adverse Event Reporting System, and Database of Adverse Event Notifications, to identify drug-associated EBA (DAEBA) cases. The databases were queried for all cases of DAEBA at any age, and patients who developed EBA following monotherapy and as one reaction term were included. Patients who were being treated for EBA were excluded. All data were reviewed by two authors, and duplicates were manually removed. Demographic information, including age, gender, reporter type, and country of report, as well as severity and clinical outcome, were extracted. Offending medications were identified and organized by medication class. After initial data extraction, a total of 118 cases were identified, of which 58 met eligibility criteria (https://data.mendeley.com/datasets/p3y84zcnhx/1). Males comprised 48.3% of cases; there was a mean age of 55.4 years for all cases, and 72.4% of cases were reported by healthcare providers worldwide (Table 1). Most reactions were classified as “serious” with 32.8% of cases requiring hospitalization and three related deaths. Immunomodulatory biologic agents were the most commonly implicated agents (24.1%), followed by antineoplastics/targeted therapy (13.8%) and immune checkpoint inhibitors (ICIs) (13.8%) (Table 2). The three deaths were associated with methotrexate, drotecogin alpha, and rituximab use. The Pfizer COVID-19 vaccine was the most commonly implicated vaccine (4/5 cases). We find a heterogeneous range of medications/vaccinations associated with DAEBA, with immunomodulatory biologic agents, antineoplastics, and ICIs being the most frequently implicated. We propose that ICI-mediated T cell activation, or biologic/antineoplastic-mediated immune dysregulation may lead to a host B cell response that triggers the production of IgG, IgA, and/or IgM antibodies, resulting in dermo-epidermal detachment [3]. Cross-reactivity in previously sensitized individuals or molecular mimicry, where drugs resemble non-self-antigens and trigger CD4+ T cell–mediated autoimmune responses, may also explain DAEBA [4]. Previous studies of drug-associated bullous pemphigoid suggested that antibiotics, anti-inflammatory drugs, and cardiovascular agents may bind to proteins in the lamina lucida of the basement membrane zone (BMZ), altering the antigenicity of the BMZ and triggering the production of anti-BMZ antibodies [4]. We find similarly implicated agents in DAEBA, whereby the offending agent may function as a hapten that alters the antigenicity of COL7 directly, releasing anti-COL7 antibodies [3]. Although the incidence of DAEBA is rare, prompt discontinuation of potential culprit medications is imperative for improved patient outcomes. Limitations of this analysis include the utilization of spontaneous adverse event reporting databases that may have incomplete and missing data, underreport total cases, and show a lack granular detail regarding diagnosis confirmation. The lack of specific AE severity scoring details and distinctions between de novo EBA versus EBA flares occurring in patients taking these medications also limit generalizability. Providers and patients can be aware that many drug classes, particularly immunomodulators and antineoplastics, may be associated with DAEBA and can be potentially discontinued or switched to alternative agents/anti-tumor therapy during disease flares when feasible. The authors have nothing to report. The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.

BK polyomavirus (BKPyV) is a common opportunistic infection in kidney transplant recipients, typically reactivating in the context of immunosuppression. Although asymptomatic in immunocompetent individuals, reactivation in transplant recipients can cause BKPyV-associated nephropathy (BKPyVAN), a leading cause of graft dysfunction and loss. BKPyV viremia affects approximately 10%-15% of transplant recipients, and once BKPyVAN is established, the risk of graft failure can exceed 50%. The current standard of care involves immunosuppression reduction to restore virus-specific immunity, but this approach increases the risk of acute and chronic rejection. Intravenous immunoglobulin (IVIg), which contains antiviral and immunomodulatory antibodies, has been proposed as an adjunctive therapy, although evidence supporting its efficacy remains limited to small observational studies. The BEAT-BK trial is a multicenter, adaptive, randomized controlled trial comparing standard immunosuppression reduction with or without IVIg in kidney and simultaneous pancreas-kidney transplant recipients with BKPyV viremia or biopsy-confirmed BKPyVAN. The trial will enroll participants aged 2 y and older, randomizing them 1:1 to receive standard care alone or in combination with a total IVIg dose of 2 g/kg for 8 wk. An adaptive Bayesian design will permit interim analyses with the potential for early trial success or futility. The primary endpoint is a composite ordinal outcome at 12 wk, incorporating death, graft loss, estimated glomerular filtration rate decline, acute rejection, viral load, and degree of immunosuppression reduction. Secondary outcomes include viral clearance, development of BKPyVAN and donor-specific antibodies, infections, malignancy, quality of life, and cost-effectiveness. This trial will provide the first high-quality evidence on the role of IVIg in BKPyV management and inform clinical decision-making in posttransplant care.

Population-based retrospective study. To compare the impact of cigarette smoking and smokeless tobacco use on postoperative outcomes after anterior cervical discectomy and fusion. Cigarette smoking has been associated with negative postoperative outcomes after anterior cervical discectomy and fusion (ACDF). While cigarette use has declined, the use of smokeless tobacco has increased. Although several studies have investigated the effects of smokeless tobacco in orthopedic surgery, limited data exist for ACDF. The Nationwide Readmissions Database was used to identify patients who underwent ACDF between 2020 and 2022. Patients were stratified as traditional tobacco users, smokeless tobacco users, and tobacco-naive. After propensity score matching, baseline characteristics and postoperative outcomes were compared across cohorts. There were no differences in postoperative outcomes between smokeless tobacco and tobacco-naive patients. Compared with tobacco-naive patients, cigarette smokers demonstrated higher odds of overall complications (OR=1.49), 180-day mortality (OR=2.72), pulmonary complications (OR=2.01), cardiovascular complications (OR=1.75), surgical complications (OR=1.23), and dysphagia (OR=1.31). Smokeless tobacco users had decreased odds of surgical complications compared with cigarette smokers (OR=0.36). In this national cohort of ACDF patients, smokeless tobacco use was not associated with increased postoperative complications compared with tobacco-naive controls, whereas cigarette smoking demonstrated consistently higher odds of adverse outcomes. When comparing tobacco modalities directly, smokeless tobacco users had no statistically significant difference compared with cigarette smokers for most postoperative complications. Further studies incorporating granular nicotine exposure data, contemporary distinctions among smokeless products, and detailed surgical variables are needed to clarify how the mode of nicotine delivery influences outcomes after ACDF. Level III.

ABSTRACT Adverse cardiometabolic factors and poor mental health in early adulthood are linked to long-term disease risk. We conducted a cross-sectional study of 2,783 adults aged 21–35 years in Puerto Rico to characterize self-reported demographic, health, and behavioral profiles and examine sex and age differences. Findings showed that 40.5% reported ≥6 days of poor mental health and 20.4% ≥6 days of poor physical health in the past month. Most participants had health insurance (90.3%), yet 36.9% reported financial barriers to care, and 32.3% lacked a primary care provider. Preventive care engagement was mixed, with low influenza vaccination (30.4%) but higher HIV/STD testing (70.7%), PAP smear screening (77.9%), and HPV vaccination (54.7%). Over half were overweight or obese (57.2%), 14.7% reported elevated levels of blood sugar or prediabetes, and 10.9% hypertension. Females reported poorer mental health but higher engagement in preventive services, whereas males were more likely to lack insurance or a primary care provider and to report hypertension and tobacco use. Younger adults reported worse mental health and higher loneliness, while older groups showed greater cardiometabolic factors. These findings highlight the need for interventions to improve preventive care, increase awareness of cardiometabolic risk, and enhance mental health among young adults.

Delay discounting, or the propensity to devalue rewards as the time to reward receipt increases, is a robust predictor of psychiatric and neurodevelopmental outcomes across the life course. However, less is known about environmental antecedents that may be associated with delay discounting tendencies during adolescence, a developmental period during which delay discounting behaviors are still developing. Here, we examined the relation between delay discounting and the exposome—multi-level environmental exposures experienced from conception onwards. Participants included 9,848 children (Mage = 10.94 years, SD = 0.64; 53.2% female; 72% White) from the Adolescent Brain Cognitive Development Study who completed the Adjusting Delay Discounting Task at the 1-year follow-up. Predictors included six exposome factors that captured aspects of proximal and distal environments including: positive day-to-day experiences, family values, household adversity, neighborhood poverty, birth/pregnancy complications, and state-level conservatism/rurality. Greater household adversity, lower positive day-to-day experiences, and greater birth/pregnancy complications were associated with greater delay discounting, after adjusting for age, sex, race, household income and parent education. These findings highlight potential intervention and policy targets aimed at modifying delay discounting preferences in adolescence and reducing risk for negative sequelae across development.