Nonalcoholic steatohepatitis Fitness Intervention in Thrombosis (NASHFit): Study protocol for a randomized controlled trial of a supervised aerobic exercise program to reduce elevated clotting risk in patients with NASH.

Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease worldwide affecting upwards of one third the global population. For reasons not fully understood, individuals with NAFLD and its more severe variant, nonalcoholic steatohepatitis (NASH), are at increased risk for venous thromboembolism which significantly increases morbidity and mortality. Lifestyle changes centering around exercise training are the mainstay of treatment for NAFLD/NASH. While exercise training can lessen venous thromboembolic risk in healthy persons and those with cardiovascular disease, whether or not this benefit is seen in patients with NAFLD/NASH remains unknown. In order to better understand how exercise training impacts thrombosis risk in NAFLD, we present the design of a thirty-two week randomized controlled clinical trial of 42 sedentary subjects age 18-69 with biopsy proven NASH. The main aim is to determine the impact of an aerobic exercise training program on the abnormal hemostatic system unique to NAFLD/NASH. The main outcome is change in plasminogen activator inhibitor one level, an established marker for venous thromboembolism. Secondary outcomes include body composition, cardiorespiratory fitness, control of comorbid metabolic conditions (e.g., obesity, hypertension, hyperlipidemia, diabetes), dietary composition, health related quality of life, liver enzymes and histology, NAFLD/NASH disease activity (e.g., biomarkers, clinical decision aids), microbiome, other markers of hemostasis, and PNPLA3 gene expression. The study represents the first clinical trial of an exercise training program to reduce elevated clotting risk in subjects with NAFLD/NASH.

Hyponatremia Is Protective Against the Development of Portal Vein Thrombosis in Patients Undergoing Liver Transplant.

BACKGROUND: Both hyponatremia and portal vein thrombosis (PVT) reflect the severity of liver dysfunction and are independently associated with increased morbidity in cirrhotic patients. In this study, we analyzed effects of hyponatremia on PVT development. METHODS: Data on adult liver transplants (LTs) in the Model for End-Stage Liver Disease era through September 2016 were obtained. Receiver operating curves and multivariable logistic regression models were constructed to evaluate the association between serum sodium level and PVT. Based on the receiver operating curves, hyponatremia was defined as a sodium level below 125 mEq/L. RESULTS: Of the 49,155 recipients included, 16% had hyponatremia (n = 7828) and 9% had PVT (n = 4414) at transplant. Subjects with hyponatremia had lower rates of PVT at the time of LT (4.4% vs 10.1%, P < .001), incidence of nonalcoholic steatohepatitis (10.8% vs 16.5%, P < .001), diabetes (19.7% vs 24.3%, P < .001), and need for dialysis (8.8% vs 16.0%, P < .001) as well as higher rates of chronic hepatitis C and B (37.6% vs 29.1%, P < .001 and 2.9% vs 1.7%, P < .001). Multivariable regression analysis confirmed that hyponatremia was independently associated with a decreased likelihood of PVT (odds ratio [OR], 0.44, P < .001). African American patients had a lower incidence of PVT (OR, 0.70; P < .001). Variables associated with a higher incidence of PVT were: nonalcoholic steatohepatitis (OR, 1.15; P = .005), moderate-to-severe ascites (OR, 1.10; P = .008), and Hispanic ethnicity (OR, 1.2; P < .001). CONCLUSION: Hyponatremia is associated with a lower rate of PVT independent of severity of liver disease and other thrombotic risk factors. This protective effect should be taken into consideration during the perioperative management of hyponatremia in patients undergoing LT.

Increased Risk of Influenza and Influenza-Related Complications Among 140,480 Patients With Inflammatory Bowel Disease.

Background: Diseases of immune dysregulation are associated with an increased risk of viral infections, some of which may be preventable. To date, there are very limited data on the incidence and risk of influenza and related complications in patients with inflammatory bowel disease (IBD). Furthermore, the impact of immunosuppressive medications on that risk is unclear. Therefore, the aim of this study was to estimate the incidence and severity of influenza infections in IBD patients. In addition, we looked specifically at the effect of medications on influenza risk. Methods: Using the MarketScan Database (January 2008 to December 2011), we conducted a retrospective cohort study to estimate the incidence of influenza and risk of related complications in IBD patients compared with those without IBD. We employed a nested case-control study design to evaluate the potential independent effect of IBD medications on influenza risk. Results: A total of 140,480 patients with IBD and non-IBD controls were studied. There were 2963 patients with influenza compared with 1941 non-IBD subjects. Inflammatory bowel disease patients had an increased influenza risk compared with those without IBD (incidence rate ratio, 1.54; 95% confidence interval [CI], 1.49-1.63). A higher rate of hospitalizations (162/2994 [5.4%] vs 36/1941 [1.85%]; P < 0.001) was noted. Systemic corticosteroids were found to be independently associated with influenza (odds ratio, 1.22; 95% CI, 1.08-1.38). Conclusions: Inflammatory bowel disease patients had an increased risk of influenza compared with those without IBD and were more likely to require hospitalization. Steroids were the only medication class independently associated with flu risk.

Influences and Impact of Anxiety and Depression in the Setting of Inflammatory Bowel Disease.

Background: Individuals with inflammatory bowel disease (IBD) are at increased risk of developing anxiety or depression (A&D). Crohn's disease (CD) and ulcerative colitis (UC) with comorbid A&D are both more challenging to manage. IBD providers need to better understand the causes and impact of A&D in order to improve care for IBD patients. We sought to identify clinical factors that influence development of A&D and healthcare utilization in IBD. Methods: This is a retrospective analysis using an IBD natural history registry from a single tertiary care referral center. Presence of A&D was determined based upon responses to the Hospital Anxiety and Depression Scale. Demographic and clinical factors were abstracted to evaluate for significant associations. Results: Four hundred thirty-two IBD patients (132 UC, 256 CD, and 44 indeterminate colitis) were included in this study. One hundred ninety-two (44.4%) had anxiety or depression or both, and most were female (59.4%, P < 0.05). History of surgery (P < 0.05), female gender (P < 0.05), smoking (P < 0.05), and extra-intestinal manifestations (P < 0.01) were each independently predictive of A&D. Inflammatory bowel disease patients with A&D more often underwent imaging studies (53.6% vs 36.7%, P < 0.05), visited the ED (30.7% vs 20.8%, P < 0.05), or were hospitalized (31.7% vs 21.7%, P < 0.05). They were also more frequently prescribed corticosteroids (50.5% vs 36.7%, P < 0.01) and biologic medications (62.5% vs 51.3%, P < 0.05). Finally, they were more likely to have had at least 1 "no-show" (29.2% vs 16.7%, P < 0.01) and had a higher mean number of "no-shows" (0.69 +/- 0.1 vs 0.30 +/- 0.1, P < 0.01) over the study period. Discussion: Anxiety and depression are common in the setting of IBD and are strongly associated with surgical history, disease complications (including extra-intestinal manifestations), smoking, and female gender. Inflammatory bowel disease patients with A&D are also more likely to require therapy and to utilize healthcare resources. This study refines our understanding of A&D development and its impact in IBD and provides additional considerations for management in this setting.

Predictors of 30-Day Mortality in Hospitalized Patients with Clostridium difficile Infection.

OBJECTIVES: Clostridium difficile infection (CDI) is a significant cause of morbidity and mortality and is the most common nosocomial infection in the United States, with associated annual costs of approximately $3 billion. The epidemiology of CDI has changed with the identification of novel risk factors for incident and recurrent CDI. The aim of this study was to identify the predictors of 30-day mortality in hospitalized patients with CDI. METHODS: We identified all of the patients diagnosed as having CDI from January 2011 to December 2014 at our university-setting hospital. Data were extracted using electronic medical records and chart review. The data of all of the patients who died within 30 days of incident CDI were compared with those who survived beyond 30 days of incident CDI. A multivariable logistic regression model was created for mortality after finding a subset of significant predictor variables by making bivariate comparisons also using logistic regression. RESULTS: A total of 893 patients were diagnosed as having CDI during the study period. The mean age was 62 years and 49.5% were women. The mean length of hospital stay was 11.73 days. Of the 893 patients with CDI, 98 (10.97%) died within 30 days of incident CDI. CDI recurrence was noted in 76 patients (8.51%). On multivariate logistic regression analysis, peptic ulcer disease, advanced age, Charlson comorbidity index, and intensive care unit status were found to be significantly associated with 30-day mortality. There was no significant association between acid suppression and CDI mortality. CONCLUSIONS: Advanced age, Charlson comorbidity index, intensive care unit status, and peptic ulcer disease are predictors of all-cause 30-day mortality in hospitalized patients with CDI.