Obesity, Chronic Stress, and Stress Reduction.

The obesity epidemic is caused by the misalignment between human biology and the modern food environment, which has led to unhealthy eating patterns and behaviors and an increase in metabolic diseases. This has been caused by the shift from a "leptogenic" to an "obesogenic" food environment, characterized by the availability of unhealthy food and the ability to eat at any time of day due to advances in technology. Binge Eating Disorder (BED) is the most commonly diagnosed eating disorder, characterized by recurrent episodes of binge eating and a sense of loss of control over eating, and is treated with cognitive-behavioral therapy-enhanced (CBT-E). Shift work, especially night shift work, can disrupt the body's natural circadian rhythms and increase the risk of obesity and other negative health consequences, such as cardiovascular disease and metabolic syndrome. One dietary approach to address circadian dysregulation is time-restricted eating (TRE), which involves restricting food intake to specific periods of the day to synchronize the body's internal clock with the external environment. TRE has been found to cause modest weight loss and improve metabolic outcomes such as insulin sensitivity and blood pressure, but the extent to which it is beneficial may depend on adherence and other factors such as caloric restriction.

A Clinical Predictive Model for One-year Colectomy in Adults Hospitalized for Severe Ulcerative Colitis.

Background: Models to predict colectomy in ulcerative colitis (UC) are valuable for identification, clinical management, and follow-up of high-risk patients. Our aim was to develop a clinical predictive model based on admission data for one-year colectomy in adults hospitalized for severe UC. Methods: We performed a retrospective analysis of patients hospitalized at a tertiary academic center for management of severe UC from 1/2013 to 4/2018. Multivariate regression was performed to identify individual predictors of one-year colectomy. Outcome probabilities of colectomy based on the prognostic score were estimated using a bootstrapping technique. Results: Two hundred twenty-nine individuals were included in the final analytic cohort. Four independent variables were associated with one-year colectomy which were incorporated into a point scoring system: (+) 1 for single class biologic exposure prior to admission; (+) 2 for multiple classes of biologic exposure; (+) 1 for inpatient salvage therapy with cyclosporine or a TNF-alpha inhibitor; (+) 1 for age <40. The risk probabilities of colectomy within one year in patients assigned scores 1, 2, 3, and 4 were 9.4% (95% CI, 1.7-17.2), 33.7% (95% CI, 23.9-43.5), 58.5% (95% CI, 42.9-74.1), 75.0% (95% CI, 50.5-99.5). An assigned score of zero was a perfect predictor of no colectomy. Conclusion: Risk factors most associated with one-year colectomy for severe UC included: prior biologic exposure, need for inpatient salvage therapy, and younger age. We developed a simple scoring system using these variables to identify and stratify patients during their index hospitalization.

Inpatient Therapy With Calcineurin Inhibitors in Severe Ulcerative Colitis.

BACKGROUND: Inpatient management of severe ulcerative colitis is complicated by the use of prior immunosuppressant therapies. Our aim was to determine the rate of 1-year colectomy among individuals receiving inpatient calcineurin inhibitor (CNI)-based therapy stratified by prior biologic therapy. METHODS: A retrospective cohort study was performed between January 1, 2013 and April 1, 2018. Only individuals requiring inpatient administration of intravenous cyclosporine or oral tacrolimus were included in the analysis. Individuals were stratified according to prior biologic therapy exposure. The primary outcome of interest was 1-year risk of colectomy. Kaplan-Meier curves were generated for time-to-event data, and regression models were performed to examine the effects of covariates on the clinical endpoint. RESULTS: Sixty-nine (62.3% male) patients were treated with an inpatient CNI-based therapy and were included in the analysis. Fifteen (21.7%) patients were biologic-naïve, 42 (60.9%) patients had prior exposure to 1 class of biologic therapy, and 12 (17.4%) patients had prior exposure to 2 classes of biologic therapy (third-line CNI therapy). Third-line CNI therapy showed a greater risk of 1-year colectomy risk when compared with the risk for patients who were biologic-naïve (hazard ratio, 3.63; 95% confidence interval, 1.17-13.45; P = 0.025). In a multivariate proportional hazards model, third-line CNI therapy remained significantly associated with 1-year colectomy risk (hazard ratio, 7.94; 95% confidence interval, 1.97-39.76; P = 0.003). CONCLUSIONS: The use of CNI-based therapy in individuals exposed to multiple classes of prior biologic therapies leads to a significantly increased risk of 1-year colectomy. Future studies will be required to compare inpatient management strategies with the expanding novel therapies in UC.

Role of Diet in the Development and Management of Crohn's Disease.

PURPOSE OF REVIEW: This article provides an updated review on the role of diet in the risk of developing Crohn's disease (CD) and CD management, areas of ongoing study. RECENT FINDINGS: Higher intake of dietary fiber (fruit fiber) has been associated with a reduced risk for CD. The exclusive enteral nutrition (EEN) diet remains the most validated nutritional recommendation for inducing remission in CD. The specific carbohydrate diet (SCD) has demonstrated reductions in CD severity scores in conjunction with medical therapies, and larger trials on its efficacy are ongoing. Several new exclusion diets modeled after EEN and SCD have shown potential efficacy in smaller studies that warrant replication. There is a paucity of clear dietary recommendations for the reduction in risk of CD clinical relapse. There are various components of diet that likely impact risk for CD development and contribute to its disease course; however, studies are often limited in their size or ability to demonstrate mechanistic causation. Further studies including diets that aim to expand on the restrictive nature of EEN may lead to stronger evidence for a diet-based approach to CD management.

Na+-sensitive elevation in blood pressure is ENaC independent in diet-induced obesity and insulin resistance.

The majority of patients with obesity, insulin resistance, and metabolic syndrome have hypertension, but the mechanisms of hypertension are poorly understood. In these patients, impaired sodium excretion is critical for the genesis of Na(+)-sensitive hypertension, and prior studies have proposed a role for the epithelial Na(+) channel (ENaC) in this syndrome. We characterized high fat-fed mice as a model in which to study the contribution of ENaC-mediated Na(+) reabsorption in obesity and insulin resistance. High fat-fed mice demonstrated impaired Na(+) excretion and elevated blood pressure, which was significantly higher on a high-Na(+) diet compared with low fat-fed control mice. However, high fat-fed mice had no increase in ENaC activity as measured by Na(+) transport across microperfused cortical collecting ducts, electrolyte excretion, or blood pressure. In addition, we found no difference in endogenous urinary aldosterone excretion between groups on a normal or high-Na(+) diet. High fat-fed mice provide a model of metabolic syndrome, recapitulating obesity, insulin resistance, impaired natriuresis, and a Na(+)-sensitive elevation in blood pressure. Surprisingly, in contrast to previous studies, our data demonstrate that high fat feeding of mice impairs natriuresis and produces elevated blood pressure that is independent of ENaC activity and likely caused by increased Na(+) reabsorption upstream of the aldosterone-sensitive distal nephron.