Faculty Bibliography

Background and study aims /UNASSIGNED:Self-expandable metallic stents (SEMS) have been increasingly used in benign conditions (e. g. strictures, fistulas, leaks, and perforations). Fully covered SEMS (FSEMS) were introduced to avoid undesirable consequences of partially covered SEMS (PSEMS), but come with higher risk of stent migration. Endoscopic suturing (ES) for stent fixation has been shown to reduce migration of FSEMS. Our aim was to compare the outcomes of FSEMS with ES (FS/ES) versus PSEMS in patients with benign upper gastrointestinal conditions. Patients and methods /UNASSIGNED:We retrospectively identified all patients who underwent stent placement for benign gastrointestinal conditions at seven US tertiary-care centers. Patients were divided into two groups: FSEMS with ES (FS/ES group) and PSEMS (PSEMS group). Clinical outcomes between the two groups were compared. Results /UNASSIGNED: = 0.005. Conclusions /UNASSIGNED:The proportion of stent migration of FS/ES and PSEMS are similar. Rates of other stent-related AEs were higher in the PSEMS group. PSEMS was associated with tissue ingrowth or overgrowth leading to difficult stent removal, and secondary stricture formation. Thus, FSEMS with ES for stent fixation may be the preferred modality over PSEMS for the treatment of benign upper gastrointestinal conditions.

Ceftazidime-avibactam and ceftolozane-tazobactam are newly approved agents for the treatment of infections caused by multidrug-resistant Gram-negative bacteria. Resistance to both agents has been described clinically. Susceptibility testing on automated systems is unavailable for either agent. Our objective was to compare the disk diffusion and Etest methods to standard broth microdilution (BMD) methods for testing ceftazidime-avibactam and ceftolozane-tazobactam against a diverse collection of carbapenem-resistantEnterobacteriaceae(CRE) and carbapenem-resistantPseudomonas aeruginosa(CRP) isolates, respectively. Among 74 ceftazidime-avibactam-susceptible and -resistant CRE isolates, BMD categorical agreement was higher with Etest (96%) than with disk diffusion (72%;P= 0.0003). Twenty-eight percent of ceftazidime-avibactam-susceptible CRE isolates were classified as resistant by disk diffusion. Results were comparable to those obtained with resistance defined genotypically. Among 72 ceftolozane-tazobactam-susceptible and -resistant CRP isolates, the levels of BMD categorical agreement with disk diffusion and Etest were 94% and 96%, respectively; the only errors identified were minor. Our findings demonstrate that Etest measurements of ceftazidime-avibactam and ceftolozane-tazobactam susceptibility correlate closely with standard BMD methods, suggesting a useful role clinically. On the other hand, disk diffusion measurements overcalled CRE resistance to ceftazidime-avibactam. A better understanding of ceftazidime-avibactam interpretive breakpoints is needed before disk diffusion is used routinely in the clinic. Until clinicians and microbiologists understand Etest and disk diffusion performance at their centers, test results should be interpreted cautiously.

OBJECTIVES/OBJECTIVE:The aim of this study was to evaluate the incidence, predictors, and associated mortality of pre-implantation, early, and late ventricular arrhythmias (VAs) in patients receiving continuous-flow left ventricular assist devices (CFLVADs). BACKGROUND:VAs are common both pre- and post-implantation of left ventricular assist devices. Limited data exist on their prognostic impact in contemporary CFLVADs. METHODS:A retrospective review was performed to identify patients who underwent CFLVAD implantation between 2000 and 2015 with 2 years of follow-up. All VAs, defined as ventricular fibrillation, ventricular tachycardia lasting >30 s, or a ventricular rhythm requiring defibrillation, were analyzed. VAs occurring within 30 days of implantation were defined as early. Recorded outcomes included death and receipt of cardiac transplant. RESULTS:A total of 517 patients were included for analysis. Early VAs were associated with a significant reduction in survival (hazard ratio: 1.83; 95% confidence interval: 1.28 to 2.61; p = 0.001) compared with patients with late or no VAs. Pre-implantation variables independently predictive of early VAs included prior cardiac surgery (odds ratio: 1.90; 95% confidence interval: 1.09 to 3.32; p = 0.023) and pre-CFLVAD ventricular tachycardia storm (odds ratio: 3.15; 95% confidence interval: 1.49 to 6.69; p = 0.003). The incidence of early VAs from 2000 to 2007 was as high as 47%, whereas the highest incidence from 2008 to 2015 was <22%. CONCLUSIONS:VAs within 30 days after CFLVAD implantation are associated with an increased risk for death. Predictors of early VAs include prior cardiac surgery and pre-CFLVAD ventricular tachycardia storm. Temporal trends have shown a decrease in VA from 2000 to 2015. Strategies to reduce arrhythmia burden shortly after CFLVAD implantation warrant further investigation.

OBJECTIVE:The objective of this study was to evaluate cross-sectional associations of sodium and potassium with BMI, waist circumference (WC), and body fat and to determine whether the nativity and/or duration of United States (US) residence modified these associations. METHODS:Sodium and potassium were derived from 24-hour diet recalls from 16,156 US participants of the 2008 to 2011 Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and from 24-hour urine in 447 HCHS/SOL participants. BMI, WC, and body fat were measured. RESULTS:higher BMI (P < 0.01) and 0.54 kg more body fat (P < 0.01). CONCLUSIONS:Sodium intake was associated with higher BMI, WC, and body fat. Potassium intake was associated with lower BMI and smaller WC among US-born participants and participants with a longer duration of US residence.

Effective screening in primary care among asylum-seekers in the US is critical as this population grows. This study aimed to evaluate disease prevalence and screening methods in this high-risk group. Two hundred ten new clients from 51 countries, plus Tibet, who were accepted into a program for asylum seekers from 2012 to 2014 were included. Screening rates and outcomes for infectious, non-communicable, and mental illnesses were evaluated. Screening rates were highest for PTSD, depression, hepatitis B, and latent tuberculosis. Seventy-one percent of clients screened positive for depression and 55 % for PTSD, followed by latent tuberculosis (41 %), hypertension (10 %), hepatitis B (9.4 %), and HIV (0.8 %). Overall screening rates were high. Point of care testing was more effective than testing that required a repeat visit. A large psychiatric and infectious disease burden was identified. These findings can inform future primary care screening efforts for asylum seekers in the US.

BACKGROUND:Obesity is a worldwide epidemic, and its prevalence is higher among Veterans in the United States. Based on our prior research, primary care teams at a Veterans Affairs (VA) hospital do not feel well-equipped to deliver effective weight management counseling and often lack sufficient time. Further, effective and intensive lifestyle-based weight management programs (e.g. VA MOVE! program) are underutilized despite implementation of systematic screening and referral at all VA sites. The 5As behavior change model (Assess, Advise, Agree, Assist, Arrange) is endorsed by the United States Preventive Service Task Force for use in counseling patients about weight management in primary care and reimbursed by Medicare. In this paper, we describe the iterative development of a technology-assisted intervention designed to provide primary care-based 5As counseling within Patient-Centered Medical Homes without overburdening providers/healthcare teams. METHODS:Thematic analyses of prior formative work (focus groups with patients [n = 54] and key informant interviews with staff [n = 25]) helped to create a technology-assisted, health coaching intervention called Goals for Eating and Moving (GEM). To further develop the intervention, we then conducted two rounds of testing with previous formative study participants (n = 5 for Round 1, n = 5 for Round 2). Each session included usability testing of prototypes of the online GEM tool, pilot testing of 5As counseling by a Health Coach, and a post-session open-ended interview. RESULTS:Three main themes emerged from usability data analyses: participants' emotional responses, tool language, and health literacy. Findings from both rounds of usability testing, pilot testing, as well as the open-ended interview data, were used to finalize protocols for the full intervention in the clinic setting to be conducted with Version 3 of the GEM tool. CONCLUSIONS:The use of qualitative research methods and user-centered design approaches enabled timely detection of salient issues to make iterative improvements to the intervention. Future studies will determine whether this intervention can increase enrollment in intensive weight management programs and promote clinically meaningful weight loss in both Veterans and in other patient populations and health systems.

Hyperleptinemia, associated with obesity, is related with immune dysfunction and carcinogenesis. Natural Killer (NK) cells, a major component of the innate immune system are mediators of anti-tumor immunity and the most actively migrating cells among leukocytes. Actin rearrangement, promoted by cofilin plays a central role in cellular migration. Leptin affects the phosphorylation-dependent activity of cofilin and thus actin remodeling. We used human NK-92 cells to explore the in vitro effects of leptin on co-localization of cofilin and F-actin and on morphological changes in NK cells. NK-92 cells were incubated with different leptin concentrations (10 and 100 ng/mL) for 30 min and 24 h and immunocytochemically stained. Results demonstrate a dose- and time-dependent influence of leptin on cellular morphology. Utilizing confocal microscopy, we observed that the co-localization of cofilin-1 and F-actin was slightly influenced by leptin. In summary, the present study demonstrates an impact of a physiological leptin stimulation on the filopodia length, and a time-dependent effect on the co-localization of cofilin and F-actin in NK-92 cells.

Humans tend to form social relationships with others who resemble them. Whether this sorting of like with like arises from historical patterns of migration, meso-level social structures in modern society, or individual-level selection of similar peers remains unsettled. Recent research has evaluated the possibility that unobserved genotypes may play an important role in the creation of homophilous relationships. We extend this work by using data from 5,500 adolescents from the National Longitudinal Study of Adolescent to Adult Health (Add Health) to examine genetic similarities among pairs of friends. Although there is some evidence that friends have correlated genotypes, both at the whole-genome level as well as at trait-associated loci (via polygenic scores), further analysis suggests that meso-level forces, such as school assignment, are a principal source of genetic similarity between friends. We also observe apparent social-genetic effects in which polygenic scores of an individual's friends and schoolmates predict the individual's own educational attainment. In contrast, an individual's height is unassociated with the height genetics of peers.