Faculty Bibliography

Background/UNASSIGNED:Bacteremia caused by extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) is associated with inadequate empirical therapy and substantial mortality in neutropenic patients. Strategies are needed to identify neutropenic patients at high risk of these infections. Methods/UNASSIGNED:We collected perianal swabs from patients undergoing hematopoietic stem cell transplantation (HSCT) from April 2014-September 2016 on admission and weekly thereafter. Patients received prophylactic levofloxacin while neutropenic. Swabs were plated onto selective agar, colonies were identified and underwent antimicrobial susceptibility testing, and phenotypic ESBL testing and PCR for β-lactamase genes were performed on ceftriaxone-resistant Enterobacteriaceae. We then determined the prevalence of pre-transplant ESBL-E colonization and risk of ESBL-E bacteremia. Colonizing and bloodstream isolates from patients with ESBL-E bacteremia underwent multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). Results/UNASSIGNED:We analyzed 312 patients, including 212 allogeneic and 100 autologous HSCT recipients. Ten percent (31/312) of patients were colonized with ESBL-E pre-transplant. Antimicrobial susceptibility rates of colonizing ESBL-E were: levofloxacin, 25%, ceftazidime: 13%, cefepime: 9%, piperacillin-tazobactam: 84%, meropenem: 97%. Ten (32%) of 31 patients colonized with ESBL-E pre-transplant developed ESBL-E bacteremia during their transplant admission, compared to one (0.4%) of 281 patients not colonized with ESBL-E (P<0.001). All bloodstream ESBL-E were levofloxacin-resistant and colonizing and bloodstream isolates from individual patients had identical MLST and PFGE profiles. Conclusions/UNASSIGNED:HSCT recipients who are colonized with levofloxacin-resistant ESBL-E pre-transplant and receive levofloxacin prophylaxis have high rates of bacteremia from their colonizing strain during neutropenia. Assessing for ESBL-E colonization in neutropenic patients may be a strategy for optimizing empirical antibacterial therapy.

Direct or indirect exposure to an explosion can induce traumatic brain injury (TBI) of various severity levels. Primary TBI from blast exposure is commonly characterized by internal injuries, such as vascular damage, neuronal injury, and contusion, without external injuries. Current animal models of blast-induced TBI (bTBI) have helped to understand the deleterious effects of moderate to severe blast forces. However, the neurological effects of mild blast forces remain poorly characterized. Here, we investigated the effects caused by mild blast forces combining neuropathological, histological, biochemical and neurophysiological analysis. For this purpose, we employed a rodent blast TBI model with blast forces below the level that causes macroscopic neuropathological changes. We found that mild blast forces induced neuroinflammation in cerebral cortex, striatum and hippocampus. Moreover, mild blast triggered microvascular damage and axonal injury. Furthermore, mild blast caused deficits in hippocampal short-term plasticity and synaptic excitability, but no impairments in long-term potentiation. Finally, mild blast exposure induced proteolytic cleavage of spectrin and the cyclin-dependent kinase 5 activator, p35 in hippocampus. Together, these findings show that mild blast forces can cause aberrant neurological changes that critically impact neuronal functions. These results are consistent with the idea that mild blast forces may induce subclinical pathophysiological changes that may contribute to neurological and psychiatric disorders.

BACKGROUND:The prevalence of global health in graduate medical education in the United States (US) has soared over the past two decades. The majority of US internal medicine and pediatric residency programs now offer global health electives abroad. Despite the prevalence of global health electives among US graduate medical programs today, challenges exist that may impact the experience for visiting trainees and/or host institutions. Previous reviews have predominately focused on experiences of undergraduate medical students and have primarily described positive outcomes. OBJECTIVES/OBJECTIVE:The aim of this study was to summarize the overall impact of global health electives on US internal medicine, medicine-pediatric, and pediatric residents, paying specific attention to any negative themes reported in the literature. METHODS:An Ovid MEDLINE and Ovid EMBASE literature search was conducted to identify studies that evaluated the effects of global health electives on US internal medicine, medicine-pediatric, and pediatric residents. FINDINGS/RESULTS:Ten studies were included. Four positive themes emerged: (1) improvement of medical knowledge, physical examination, and procedural skills, (2) improvement in resourcefulness and cost-effectiveness, (3) improvement in cultural and interpersonal competence, and (4) professional and career development. Two negative themes were identified: (1) health risks and (2) safety risks. CONCLUSIONS:Global health electives provide a number of perceived benefits for US medical trainees; however, we importantly highlight health and safety concerns described while abroad. Global health educators should recognize the host of unique challenges experienced during a global health elective and investigate how to best mitigate these concerns. Incorporation of mandatory pre-, intra-, and post-elective training programs and establishment of universally adopted global health best practice guidelines may serve to address some the challenges visiting trainees encounter while abroad.

Aims:Pathologic evidence supports unique sex-specific mechanisms as precursors for acute cardiovascular (CV) events. Current evidence on long-term CV risk among women when compared with men based on measures of coronary artery calcium (CAC) remains incomplete. Methods and results:A total of 63 215 asymptomatic women and men were enrolled in the multicentre, CAC Consortium with median follow-up of 12.6 years. Pooled cohort equation (PCE) risk scores and risk factor data were collected with the Agatston score and other CAC measures (number of lesions and vessels, lesion size, volume, and plaque density). Cox proportional hazard models were employed to estimate CV mortality (n = 919). Sex interactions were calculated. Women and men had average PCE risk scores of 5.8% and 9.1% (P < 0.001). Within CAC subgroups, women had fewer calcified lesions (P < 0.0001) and vessels (P = 0.017), greater lesion size (P < 0.0001), and higher plaque density (P = 0.013) when compared with men. For women and men without CAC, long-term CV mortality was similar (P = 0.67), whereas detectable CAC was associated with 1.3-higher hazard for CV death among women when compared with men (P < 0001). Cardiovascular mortality was higher among women with more extensive, numerous, or larger CAC lesions. The relative hazard for cardiovascular disease (CVD) mortality for women and men was 8.2 vs. 5.1 for multivessel CAC, 8.6 vs. 5.9 for ≥5 CAC lesions, and 8.5 vs. 4.4 for a lesion size ≥15 mm3, respectively. Additional explorations revealed that women with larger sized and more numerous CAC lesions had 2.2-fold higher CVD mortality (P < 0.0001) as compared to men. Moreover, CAC density was not predictive of CV mortality in women (P = 0.51) but was for men (P < 0.001), when controlling for CAC volume and cardiac risk factors. Conclusion:Our overall findings support that measures beyond the Agatston score provide important clues to sex differences in atherosclerotic plaque and may further refine risk detection and focus preventive strategies of care.

BACKGROUND:Medically underserved or low socioeconomic status (SES) patients face significant vulnerability and a high risk of adverse events following hospital discharge. The environmental, social, and economic factors, otherwise known as social determinants, that compound this risk have been ineffectually described in this population. As the underserved comprise 30% of patients discharged from the hospital, improving transitional care and preventing readmission in this group has profound quality of care and financial implications. METHOD/METHODS:EMBASE and MEDLINE searches were conducted to examine specific barriers to care transitions in underserved patients following an episode of acute care. Articles were reviewed for barriers and categorized within the context of five general themes. RESULTS:This review yielded 17 peer-reviewed articles. Common factors affecting care transitions were cost of medications, access to care, housing instability, and transportation. When categorized within themes, social fragility and access failures, as well as therapeutic misalignment, disease behavior, and issues with accountability were noted. DISCUSSION/CONCLUSIONS:Providers and health systems caring for medically underserved patients may benefit through dedicating increased resources and broadening collaboration with community partners in order to expand health care access and enhance coordination of social services within this population. Future studies are needed to identify potential interventions targeting underserved patients to improve their post-hospital care.