Faculty Bibliography

The balance between protein synthesis and degradation regulates the amount of expressed proteins. This protein turnover is usually quantified as the protein half-life time. Several studies suggest that protein degradation decreases with age and leads to increased deposits of damaged and non-functional proteins. Glycation is an age-dependent, non-enzymatic process leading to posttranslational modifications, so-called advanced glycation endproducts (AGE), which usually damage proteins and lead to protein aggregation. AGE are formed by the Maillard reaction, where carbonyls of carbohydrates or metabolites react with amino groups of proteins. In this study, we quantified the half-life time of two important receptors of the immunoglobulin superfamily, the neural cell adhesion molecule (NCAM) and the receptor for advanced glycation end products (RAGE) before and after glycation. We found, that in two rat PC12 cell lines glycation leads to increased turnover, meaning that glycated, AGE-modified proteins are degraded faster than non-glycated proteins. NCAM is the most prominent carrier of a unique enzymatic posttranslational modification, the polysialylation. Using two PC12 cell lines (a non-polysialylated and a polysialylated one), we could additionally demonstrate, that polysialylation of NCAM has an impact on its turnover and that it significantly increases its half-life time.

BACKGROUND:Hepatitis B virus is a viral infection that can lead to acute and/or chronic liver disease, and hepatocellular carcinoma (HCC). Hepatitis B vaccination is 95% effective in preventing infection and the development of chronic liver disease and HCC due to hepatitis B. In 2011, the Centers for Disease Control updated their guidelines recommending that adults at high-risk for hepatitis B infection be vaccinated against hepatitis B including those with diabetes mellitus (DM). We hypothesize that adults at high-risk for hepatitis B infection are not being adequately screened and/or vaccinated for hepatitis B in a large urban healthcare system. AIM/OBJECTIVE:To investigate clinical factors associated with Hepatitis B screening and vaccination in patients at high-risk for Hepatitis B infection. METHODS:We conducted a retrospective review of 999 patients presenting at a large urban healthcare system from 2012-2017 at high-risk for hepatitis B infection. Patients were considered high-risk for hepatitis B infection based on hepatitis B practice recommendations from the Center for Disease Control. Medical history including hepatitis B serology, concomitant medical diagnoses, demographics, insurance status and social history were extracted from electronic health records. Multivariate logistic regression was used to identify clinical risk factors independently associated with hepatitis B screening and vaccination. RESULTS:< 0.05. CONCLUSION/CONCLUSIONS:Patients at high-risk for hepatitis B are not being adequately screened and/or vaccinated. Improvements in hepatitis B vaccination should be strongly encouraged by all healthcare systems.

Introduction Cholangiocarcinoma is an aggressive and rare cancer of the bile duct with a very poor prognosis. It accounts for approximately three percent of gastrointestinal cancers but nearly 20 percent of deaths are from hepatobiliary cancers. Cholangiocarcinoma is also a clinically silent disease that presents at advanced stages. In this study, we wanted to identify subpopulations at the greatest risk of developing cholangiocarcinoma such that we can improve diagnosis and ultimately reduce the cancer mortality rate. Methods The United States Cancer Registry (USCS) was used to obtain data for cholangiocarcinoma from 2001 to 2015. Incidence analysis was done for sex, race, stage, primary location (intrahepatic bile duct or extrahepatic bile duct), and US regional location. Results The overall incidence of cholangiocarcinoma from 2001 to 2015 was 1.26 per 100,000 people per year. The overall incidence rates were greatest for each stratification in males, Asian and Pacific Islanders (API), distant disease, intrahepatic bile duct cholangiocarcinoma (ICC), and in the Northeast. Incidence rates were increasing between 2001 and 2015 in all subpopulations. Compared to extrahepatic bile duct cholangiocarcinoma (ECC), ICC increased significantly between 2001 and 2015. From 2001 to 2007, the annual percent change (APC) for ICC was 2.79, from 2007 to 2010 the APC was 17.02, and from 2010 to 2015 the APC was 9.67. Moreover, the incidence of distant disease also increased significantly with an APC of 9.22. Conclusion In our study, we analyzed the incidence of cholangiocarcinoma in all 50 states in the USA. We found that the incidence is increasing in all subpopulations and specifically at a dramatic rate for ICC and those with distant disease at the time of diagnosis. Ultimately, our findings identified at-risk populations who need closer monitoring for cholangiocarcinoma.

There has been increasing interest in the human anaerobic colonic bacterium Oxalobacter formigenes because of its ability to metabolize oxalate, and its potential contribution to protection from calcium oxalate kidney stones. Prior studies examining the prevalence of this organism have focused on subjects in developed countries and on adults. Now using O. formigenes-specific PCR, we have compared the prevalence of these organisms among subjects in two remote areas in which modern medical practices have hardly been present with a USA group of mothers and their infants for the first three years of life. Among the Amerindians of the Yanomami-Sanema and Yekwana ethnic groups in Venezuela and the Hadza in Tanzania, O. formigenes was detected in 60-80% of the adult subjects, higher than found in adults from USA in this and prior studies. In young children, the prevalence was much lower in USA than in either tribal village. These data extend our understanding of the epidemiology of O. formigenes carriage, and are consistent with the hypothesis that the rising incidence of kidney stones is associated with the progressive loss of O. formigenes colonization in populations that have been highly impacted by modern medical practices.

The Accreditation Council for Graduate Medical Education requires integration of quality improvement and patient safety education into graduate medical education (GME). The authors created a novel "Swiss Cheese Conference" to bridge the gap between GME and hospital patient safety initiatives. Residents investigate a specific patient safety event and lead a monthly multidisciplinary conference about the case. Resident presenters introduce the Swiss cheese model, present the case and their findings, and teach a patient safety topic. In groups, participants identify contributing factors and discuss how to prevent similar events. Presenters and stakeholders immediately huddle to identify next steps. The Swiss Cheese Conference has increased participants' comfort analyzing safety issues from a systems perspective, utilizing the electronic reporting system, and launching patient safety initiatives. The Swiss Cheese Conference is a successful multidisciplinary model that engages GME trainees by integrating resident-led, case-based quality improvement education with creation of patient safety initiatives.

BACKGROUND:HLA-B*57:01 screening was added to clinical care guidelines in 2008 to reduce the risk of hypersensitivity reaction from abacavir. The uptake of HLA-B*57:01 screening and incidence of hypersensitivity reaction were assessed in a prospective clinical cohort in the United States to evaluate the effectiveness of this intervention. METHODS:We included all patients initiating an abacavir-containing regimen for the first time in the pre-HLA-B*57:01 screening period (January 1, 1999 to June 14, 2008) or the post-HLA-B*57:01 screening period (June 15, 2008 to January 1, 2016). Yearly incidence of both HLA-B*57:01 screening and physician panel-adjudicated hypersensitivity reactions were calculated and compared. RESULTS:Of the 9619 patients eligible for the study, 33% initiated abacavir in the pre-screening period and 67% in the post-screening period. Incidence of HLA-B*57:01 screening prior to abacavir initiation increased from 43% in 2009 to 84% in 2015. The incidence of definite or probable hypersensitivity reactions decreased from 1.3% in the pre-screening period to 0.8% in 2009 and further to 0.2% in 2015 in the post-screening period. CONCLUSIONS:Frequency of HLA-B*57:01 screening increased steadily since its first inclusion in treatment guidelines in the United States. This increase in screening was accompanied by a decreasing incidence of definite or probable hypersensitivity reactions over the same period. However, a considerable proportion of patients initiating abacavir were not screened, representing a failed opportunity to prevent hypersensitivity reactions. Where HLA-B*57:01 screening is standard of care, patients should be confirmed negative for this allele before starting abacavir treatment.

Many hospitalists incorporate point-of-care ultrasound (POCUS) into their daily practice to answer specific diagnostic questions or to guide performance of invasive bedside procedures. However, standards for hospitalists in POCUS training and assessment are not yet established. Most internal medicine residency training programs, the major pipeline for incoming hospitalists, have only recently begun to incorporate POCUS in their curricula. The purpose of this document is to inform a broad audience on what POCUS is and how hospitalists are using it. This document is intended to provide guidance for the hospitalists who use POCUS and administrators who oversee its use. We discuss POCUS 1) applications, 2) training, 3) assessments, and 4) program management. Practicing hospitalists must continue to collaborate with their local credentialing bodies to outline requirements for POCUS use. Hospitalists should be integrally involved in decision-making processes surrounding POCUS program management.