Citations

Purpose To explore the relationship between alcohol abuse/dependence with burnout and other forms of distress among a national cohort of medical students. Method In 2012, the authors completed a national survey of medical students from the American Medical Association’s Physician Masterfile containing validated items assessing alcohol abuse/dependence, burnout, depression, suicidality, quality of life (QOL), and fatigue. Descriptive and comparative statistical analyses were computed, including chi-square and multivariate logistic regression, to determine relationships between variables. Results Of the 12,500 students, 4,402 (35.2%) responded. Of these, 1,411 (32.4%) met diagnostic criteria for alcohol abuse/dependence. Students who were burned out ( P = .01), depressed ( P = .01), or reported low mental ( P =.03) or emotional ( P = .016) QOL were more likely to have alcohol abuse/dependence. Emotional exhaustion and depersonalization domains of burnout were strongly associated with alcohol abuse/dependence. On multivariate analysis, burnout (OR 1.20; 95% CI 1.05–1.37; P < .01), having $50,000 to $100,000 (OR 1.21 versus < $50,000; CI 1.02–1.44; P < .05) or > $100,000 (OR 1.27 versus < $50,000; CI 1.08–1.48; P < .01) of educational debt, being unmarried (OR 1.89; CI 1.57–2.27; P < .001), and being younger (for every five years, OR 1.15; CI 1.02–1.28; P = .01) were independently associated with increased risk for alcohol abuse/dependence. Conclusions Burnout was strongly related to alcohol abuse/dependence among sampled medical students and increased educational debt predicted a higher risk. A multifaceted approach addressing burnout, medical education costs, and alcohol use is needed.

ABSTRACTBackgroundPatients with sinus node dysfunction (SND) have increased risk of atrial tachyarrhythmias, including atrial fibrillation (AF). To date, treatment patterns and outcomes of patients with SND and AF have not been well described.HypothesisPatients with SND and AF have higher risk of adverse cardiovascular outcomes.MethodsSinus node dysfunction was defined clinically, based on treating physician. Treatment patterns were described and logistic regression analysis performed to assess outcomes.ResultsOverall, 1710 (17.7%) out of 9631 patients had SND at enrollment. Patients with SND and AF had increased comorbid medical illnesses, more severe symptoms (European Heart Rhythm Association class IV: 17.5% vs 13.9%; P = 0.0007), and poorer quality of life (median 12‐month Atrial Fibrillation Effect on Quality of Life score: 79.6 vs 85.2; P = 0.0008). There were no differences in AF management strategy between patients with SND and those without (rate control, 69.7% vs 67.7%; rhythm control, 30.0% vs 32.0%; P = 0.11). After adjustment, patients with SND were more likely than those without SND to progress from paroxysmal AF at baseline to persistent or permanent AF at any follow‐up, or persistent AF at baseline to permanent AF at any follow‐up (odds ratio: 1.23, 95% confidence interval: 1.01‐1.49, P = 0.035). However, there was no association between SND and major risk‐adjusted outcomes.ConclusionsSinus node dysfunction is present in 1 of 6 patients with AF and is associated with increased comorbidities and higher symptom burden. However, SND is not associated with an increase in major risk‐adjusted outcomes.

AbstractAiming to decipher immunological mechanisms of the autoimmune disorder alopecia areata (AA), we hypothesized that interleukin‐6 (IL‐6) might be associated with juvenile‐onset AA, for which there is currently no experimental model. Upon intramuscular transgenesis to overexpress IL‐6 in pregnant female C57BL/6 (B6) mice, we found that the offspring displayed an initial normal and complete juvenile hair growth cycle, but developed alopecia around postnatal day 18. This alopecia was patchy and reversible (non‐scarring) and was associated with upregulation of Ulbp1 expression, the only mouse homolog of the human AA‐associated ULBP3 gene. Alopecia was also associated with inflammatory infiltration of hair follicles by lymphocytes, including alpha‐beta T cells, which contributed to surface hair loss. Despite these apparently shared traits with AA, lesions were dominated by follicular dystrophy that was atypical of human AA disease, sharing some traits consistent with B6 alopecia and dermatitis. Additionally, juvenile‐onset alopecia was followed by complete, spontaneous recovery of surface hair, without recurrence of hair loss. Prolonging exposure to IL‐6 prolonged the time to recovery, but once recovered, repeating high‐dose IL‐6 exposure de novo did not re‐induce alopecia. These data suggest that although substantial molecular and cellular pathways may be shared, functionally similar alopecia disorders can occur via distinct pathological mechanisms.

ABSTRACT Varicella-zoster virus (VZV) is a highly neurotropic virus that can cause infections in both the peripheral nervous system and the central nervous system. Several studies of VZV reactivation in the peripheral nervous system (herpes zoster) have been published, while exceedingly few investigations have been carried out in a human brain. Notably, there is no animal model for VZV infection of the central nervous system. In this report, we characterized the cellular environment in the temporal lobe of a human subject who recovered from focal VZV encephalitis. The approach included not only VZV DNA/RNA analyses but also a delineation of infected cell types (neurons, microglia, oligodendrocytes, and astrocytes). The average VZV genome copy number per cell was 5. Several VZV regulatory and structural gene transcripts and products were detected. When colocalization studies were performed to determine which cell types harbored the viral proteins, the majority of infected cells were astrocytes, including aggregates of astrocytes. Evidence of syncytium formation within the aggregates included the continuity of cytoplasm positive for the VZV glycoprotein H (gH) fusion-complex protein within a cellular profile with as many as 80 distinct nuclei. As with other causes of brain injury, these results suggested that astrocytes likely formed a defensive perimeter around foci of VZV infection (astrogliosis). Because of the rarity of brain samples from living humans with VZV encephalitis, we compared our VZV results with those found in a rat encephalitis model following infection with the closely related pseudorabies virus and observed similar perimeters of gliosis. IMPORTANCE Investigations of VZV-infected human brain from living immunocompetent human subjects are exceedingly rare. Therefore, much of our knowledge of VZV neuropathogenesis is gained from studies of VZV-infected brains obtained at autopsy from immunocompromised patients. These are not optimal samples with which to investigate a response by a human host to VZV infection. In this report, we examined both flash-frozen and paraffin-embedded formalin-fixed brain tissue of an otherwise healthy young male with focal VZV encephalitis, most likely acquired from VZV reactivation in the trigeminal ganglion. Of note, the cellular response to VZV infection mimicked the response to other causes of trauma to the brain, namely, an ingress of astrocytes and astrogliosis around an infectious focus. Many of the astrocytes themselves were infected; astrocytes aggregated in clusters. We postulate that astrogliosis represents a successful defense mechanism by an immunocompetent human host to eliminate VZV reactivation within neurons.

Abstract Background. The salivary gland is one of the most common sites involved by nongastric, extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT). A large series of patients with long-term follow-up has not been documented. This multicenter, international study sought to characterize the clinical characteristics, treatment, and natural history of salivary gland MALT lymphoma. Methods. Patients with biopsy-confirmed salivary gland MALT lymphoma were identified from multiple international sites. Risk factors, treatment, and long-term outcomes were evaluated. Results. A total of 247 patients were evaluated; 76% presented with limited-stage disease. There was a history of autoimmune disorder in 41%, with Sjögren disease being the most common (83%). Fifty-seven percent of patients were initially treated with local therapy with surgery, radiation, or both; 37 of patients were treated with systemic therapy initially, with 47% of those receiving rituximab; and 6% of patients were observed. The median overall survival (OS) was 18.3 years. The median progression-free survival (PFS) following primary therapy was 9.3 years. There was no difference in the outcomes between patients receiving local or systemic therapy in first-line management. On multivariate analysis, age &lt;60 years and low to intermediate international prognostic index were associated with improved OS and PFS; Sjögren disease was associated with improved OS. Conclusion. Salivary gland MALT lymphoma has an excellent prognosis regardless of initial treatment, and patients with Sjögren disease have improved survival. Risks for long-term complications must be weighed when determining initial therapy. Implications for Practice: Patients with salivary gland extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) have an excellent prognosis, particularly those with associated Sjögren's disease. A wide range of available therapies may provide similar durable rates of disease control and survival. Therefore, an important goal in selection of therapy should be to minimize morbidity from treatment. When determining initial therapy for these patients, practitioners should consider the potential side effects and long-term toxicities of treatment.