Impact of metabolic syndrome on the hospitalization rate of Crohn's disease patients seen at a tertiary care center: a retrospective cohort study.

BACKGROUND/AIMS: Recent studies suggest that markers of mesenteric inflammation, such as increased adipose tissue, may be associated with poor outcomes in Crohn's disease (CD). This study's hypothesis is that CD patients with metabolic syndrome (MetS) have more CD-related hospitalizations than CD patients without MetS. METHODS: We conducted a retrospective cohort study of CD patients seen from 2000 to 2012 at our tertiary care center. We analyzed crude and age-, sex- and duration of CD-adjusted incidence rate ratio (IRR) of CD-related hospitalization of those with MetS versus those without MetS. We also investigated possible associations between individual component conditions of MetS and rate of CD-related hospitalization. RESULTS: A total of 868 CD patients were included. There were 37 (4%) patients with MetS at initial observation. After multi-variable adjustment, patients with MetS had a CD-related hospitalization rate twice that of those who did not have MetS. High triglycerides (TG), low high density lipoprotein (HDL) cholesterol and diabetes mellitus (DM) were associated with increased risk of CD-related hospitalization. CONCLUSIONS: CD patients with MetS have a higher rate of CD-related hospitalization compared to those without MetS. Hypertriglyceridemia, low HDL cholesterol and DM may be good markers of local and systemic inflammation as seen in CD.

An efficient synthesis of 3-OBn-6ß,14-epoxy-bridged opiates from naltrexone and identification of a related dual MOR inverse agonist/KOR agonist.

In an effort to better understand the conformational preferences that inform the biological activity of naltrexone and related naltrexol derivatives, a new synthesis of the restricted analog 3-OBn-6ß,14-epoxymorphinan 4 is described. 4 was synthesized starting from naltrexone in 50% overall yield, proceeding through the OBn-6α-triflate intermediate 8. Key steps to the synthesis include benzylation (96% yield), reduction (90% yield, α:ß:3:2), followed by a one-pot triflation/displacement sequence (96% yield) to yield the desired bridged epoxy derivative 4. X-ray crystallographic analysis of intermediate 3-OBn-6α-naltrexol 7a supports population of the key boat conformation required for the epoxy ring closure. We also report that the 6ß-mesylate 10-a high affinity opioid receptor ligand, the epimeric derivative of 11, and an analog of 12-functions as an inverse agonist at the mu opioid receptor using herkinorin pre-conditioned cells and an agonist at the kappa opioid receptor when evaluated in independent in vitro [(35)S]-GTP-γ-S assays.

Association of Pulsatility with Gastrointestinal Bleeding in a Cohort of HeartMate II Recipients.

Gastrointestinal bleeding (GIB) is common in patients with continuous-flow left ventricular assist devices (CF-LVADs) possibly because of changes in blood flow. We aimed to test the hypothesis that a low pulsatility index (PI) is associated with an increased hazard of overt GIB in patients with CF-LVADs. We conducted a retrospective cohort study of patients who had a HeartMate II (HMII) CF-LVAD implanted at our center. The study end-point was the first overt GIB causing or occurring during a hospitalization between 6 days and 6 months after HMII implantation. HMII PI was recorded at 48 hours and at 1, 3, and 6 month intervals after implantation. We analyzed the associations of PI and clinical variables with the hazard of overt GIB. Ninety-five patients met eligibility criteria. PI ranged from 2.5 to 5.9 (low PI < 4.15 and high PI ≥ 4.15 on the basis of receiver operating characteristic curve analysis). Seventeen (18%) patients experienced overt GIB. In a multivariable model, only lower baseline hemoglobin was a significant predictor of an increased hazard of overt GIB. After adjusting for the baseline hemoglobin, low PI was independently associated with an increased hazard of overt GIB in our cohort of HMII recipients.

Socioeconomic Status and Race are both Independently associated with Increased Hospitalization Rate among Crohn's Disease Patients.

Racial disparities are observed clinically in Crohn's Disease (CD) with research suggesting African Americans (AA) have worse outcomes than Caucasian Americans (CA). The aim of this study is to assess whether socioeconomic status (SES) rather than race is the major predictor of worse outcomes. We designed a retrospective cohort study of 944 CD patients seen at our center. Patients' billing zip codes were collected and average income and percent of population living above or below poverty level (PL) for each zip code calculated. Patients were separated by quartiles using average state income level and federal PL. Demographics and hospitalization rates were collected. Poison regression models estimated incidence rate ratios (IRR) for CD-related hospitalizations. Incidence rate (IR) of hospitalization per 100-person years for the lowest income group was 118 (CI 91.4-152.3), highest income group was 29 (CI 21.7-38.9), Above PL was 26.9 (25.9-28.9), Below PL was 35.9 (33.1-38.9), CA was 25.3 (23.7-27), and AA was 51.4 (46.8-56.3). IRR for a CD-related hospitalization for lowest income group was 2.01 (CI 1.34-3.01), for Below PL was 1.26 (CI 1.12-1.42), and for AAs was 1.88 (CI 1.66-2.12). SES and race are both associated with hospitalization among CD patients and need further investigation.

Effect of Hepatitis C Treatment on Renal Function in Liver Transplant Patients.

Background and Aims: Hepatitis C Virus (HCV) is uniformly recurrent after liver transplant (LT) and recurrence is associated with an increased risk of mortality. Immunosuppressive medications increase the risk of chronic kidney disease, and the presence of chronic kidney disease presents a challenge for HCV treatment in LT recipients. The aim of this study was to assess changes in glomerular filtration rates (GFRs) of LT recipients receiving HCV treatment. Methods: This is a retrospective study of LT patients who received HCV treatment between 2015 and 2016 (n = 60). The outcomes of interest were differences in serum creatinine levels and in GFR, measured at treatment initiation and at 24 weeks after treatment. The average age of the patients was 59 years-old, and 17% were cirrhotic and 67% were treatment-experienced. All patients received sofosbuvir/ledipasvir without ribavirin. Results: All patients achieved sustained virologic response at 12 weeks after treatment (SVR12). At baseline, 55% of patients had GFR <60 mL/min per 1.73 m2. Among those patients, GFR did not change in 18%, 33% had improved GFR, and 48% had worsened GFR. Up to 45% of the patients had a GFR >60 mL/min per 1.73 m2. Among those patients, GFR did not change in 81%, and 19% had worsened GFR. In the entire cohort, 65% of patients had improved or stable GFR and 35% had worsened GFR. The average change in serum creatinine between baseline and 24 weeks was 0.10 (p = 0.18). Conclusions: This study showed improved or unchanged GFR in 65% and worsened GFR in 35% of LT recipients who achieved SVR12. Worsening of GFR was more frequently encountered in those with impaired renal function at baseline. Caution should be used when treating HCV in LT recipients, especially those with baseline status of renal impairment.

Biomarkers of Renal Injury in Cirrhosis: Association with Acute Kidney Injury and Recovery after Liver Transplantation.

BACKGROUND: To define urine or serum biomarkers in predicting renal function recovery after liver transplantation (LT). METHODS: Adults listed for LT (February 2011-July 2014) and with modified diet for renal disease-6 (MDRD-6) <60 mL/min provided urine/blood samples at baseline and serially until LT for biomarkers in serum (pg/mL) and urine (pg/mg creatinine). RESULTS: Of 271 LT listed patients (mean age 57 years, 63% males, median listing MELD 17.5), 1 year acute kidney injury (AKI) probability was 49%, with odds of 1.3-, 3.0-, 4.6-, and 8.5-fold times for listing MELD 16-20, 21-25, 26-30, and >30, compared to MELD <16. Thirty-seven people died over 1 year from the time of listing, with twofold increased odds with AKI. Among 67 patients with MDRD <60, only urinary epidermal growth factor was different comparing AKI (increase in serum creatinine ≥0.3 mg/dL from baseline within past 3 months) vs. no AKI (2,254 vs. 4,253, p = 0.003). Differences between acute tubular necrosis (ATN) and hepatorenal syndrome could not be ascertained for a small sample of 3 patients with ATN. Analyzing 15 of 43 receiving LT and MDRD-6 <30 prior to LT, biomarkers were not different comparing 5 patients recovering renal function (MDRD-6 >50 mL/min) at 6 months vs. 10 without recovery. CONCLUSIONS: AKI is common among LT listed patients, with a negative impact on transplant-free survival. Serum and urine biomarkers are not associated with the recovery of renal function after LT. Multicenter studies are suggested to (a) develop strategies to reduce the development of AKI and (b) derive novel biomarkers for use in accurately predicting renal recovery after LT.

Short article: Alcohol and substance use, race, and insurance status predict nontreatment for hepatitis C virus in the era of direct acting antivirals: a retrospective study in a large urban tertiary center.

OBJECTIVE: Direct acting antivirals (DAAs) have overcome many long-standing medical barriers to hepatitis C virus (HCV) treatment (i.e. host characteristics and medical contraindications) and treatment outcome disparities that were associated with interferon regimens. The public health and clinical benefit of current and forthcoming DAA discoveries will be limited if efforts are not made to examine racial, psychological, and socioeconomic factors associated with being treated with DAAs. This study examined racial, psychological, and socioeconomic factors that facilitate and inhibit patients receiving DAAs for HCV. PATIENTS AND METHODS: This was a single-center retrospective cohort study at a large urban tertiary center of patients (n=747) who were referred for evaluation and treatment of HCV. RESULTS: Sixty-eight percent of patients were non-Hispanic White, 31% were African American, and 1% were of other ethnicities. The majority of patients received treatment, but 29% (218/747) did not. Patients who were older [odds ratio (OR)=1.02, 95% confidence interval (CI): 1.01-1.04] and insured (OR=2.73, 95% CI: 1.12-6.97) were more likely to receive HCV treatment. Patients who were African American (OR=0.46, 95% CI: 0.46-1.06), used drugs (OR=0.09, 95% CI: 0.04-0.17), smoked (OR=0.55, 95% CI: 0.37-0.81), and used alcohol (OR=0.11, 95% CI: 0.06-0.20) were less likely to receive HCV treatment. CONCLUSION: Though DAAs have eliminated many historically, long-standing medical barriers to HCV treatment, several racial, psychological and socioeconomic barriers, and disparities remain. Consequently, patients who are African American, uninsured, and actively use drugs and alcohol will suffer from increased HCV-related morbidity and mortality in the coming years if deliberate public health and clinical efforts are not made to facilitate access to DAAs.

Rates of hospitalization among African American and Caucasian American patients with Crohn's disease seen at a tertiary care center.

BACKGROUND: There is equivocal evidence regarding differences in the clinical course and outcomes of Crohn's disease (CD) among African Americans compared with Caucasian Americans. We sought to analyze whether African Americans with CD are more likely to be hospitalized for CD-related complications when compared with Caucasian Americans with CD. METHODS: We conducted a retrospective cohort study including 909 African Americans and Caucasian Americans with CD who were seen at our tertiary care Inflammatory Bowel Disease (IBD) referral center between 2000 and 2013. We calculated the rate of hospitalization for CD-related complications among African Americans and Caucasian Americans separately. Zero-inflated Poisson regression models with robust variance estimates were used to estimate crude and multivariable adjusted rate ratios (RR) for CD-related hospitalizations. Multivariable adjusted models included adjustment for age, sex, duration of CD, smoking and CD therapy. RESULTS: The cumulative rate of CD-related hospital admissions was higher among African American patients compared with Caucasian American patients (395.6/1000 person-years in African Americans vs. 230.4/1000 person-years in Caucasian Americans). Unadjusted and multivariable adjusted rate ratios for CD-related hospitalization comparing African Americans and Caucasian Americans were 1.59 (95% confidence interval [95%CI]: 1.10-2.29; P=0.01) and 1.44 (95%CI: 1.02-2.03; P=0.04), respectively. CONCLUSIONS: African Americans with CD followed at a tertiary IBD-referral center had a higher rate for CD-related hospitalizations compared with Caucasian Americans. Future studies should examine whether socioeconomic status and biologic markers of disease status could explain the higher risk observed among African Americans.

Surveillance and Diagnosis of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is an important cause of cancer-related death worldwide. If the disease is detected early, the treatment is more likely to be curative. This article discusses the current evidence regarding the surveillance and diagnosis of HCC, focusing on recent articles and the recommendations of the American Association for the Study of Liver Diseases (AASLD), which are briefly compared with the recommendations of other liver disease organizations. HCC surveillance aims to detect disease at an early stage in order to augment the likelihood of curative treatment. According to AASLD recommendations, patients who have cirrhosis and those who do not have cirrhosis but are at high risk for HCC should be screened. Ultrasonogra-phy (USG) at 6-month intervals is recommended. The available serologic markers, including serum alpha-fetoprotein, are inadequate for surveillance, even when combined with USG. Despite achievements in HCC management, physicians continue to underutilize surveillance. Quadruple-phase, contrast-enhanced computed tomography scans or magnetic resonance images with characteristic radiologic findings are commonly used to diagnose HCC in suspicious cases. The available surveillance and diagnostic tests effectively identify HCC at an early stage, and as a result, the chances of cure are increased. Physicians caring for patients who have cirrhosis and chronic liver disease should be familiar with HCC surveillance recommendations and the prognostic importance of early diagnosis.