Emergency department utilisation for inflammatory bowel disease in the United States from 2006 to 2014.

BACKGROUND: Despite advances in treatment, patients with inflammatory bowel disease (IBD) frequently require emergency department (ED) visits and hospitalisations. AIMS: To analyse trends in ED visits and subsequent hospitalisations for IBD in the United States (US). METHODS: Data were analysed from the Nationwide Emergency Department Sample (NEDS) years 2006-2014. The NEDS is the largest all-payer ED database in the US, weighted to represent 135 million visits/year. IBD was identified using ICD-9 codes for Crohn's disease (CD) or ulcerative colitis (UC). Surgeries were identified using procedure codes. RESULTS: The frequency of IBD-ED visits increased 51.8%, from 90 846 visits in 2006 to 137 946 in 2014, which was statistically significant in linear regression. For comparison, all-case ED use between 2006 and 2014 increased 14.8%. In-patient hospitalisations from the ED decreased 12.1% for IBD (from 64.7% rate of hospitalisation from the ED in 2006 to 52.6% in 2014), with a UC:CD ratio of 1.2:1 in 2006 and 1.3:1 in 2014. Chi-square analysis revealed that this was a significant decrease. Surgery rates also showed a statistically significant decrease. The mean ED charge per patient rose 102.5% and the aggregate national cost of IBD-ED visits increased 207.5%. CD accounted for over twice as many visits as UC in both years. UC, age, male gender, highest income quartile, private insurance, Medicaid/Medicare, and tobacco use were associated with in-patient admissions. CONCLUSIONS: The number of ED visits due to IBD and associated charges have continued to rise, while the rates of in-patient hospitalisations referred from the ED and surgeries have decreased.

A rare case series of concomitant inflammatory bowel disease, sporadic adenomas, and serrated polyposis syndrome.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) involving the colon is associated with an increased risk of colon cancer. Patients may develop sporadic adenomas further increasing their risk of colorectal cancer. Current knowledge of IBD with concomitant serrated polyposis syndrome (SPS) is limited. We describe four patients with both IBD and SPS. METHODS: Four patients with inflammatory bowel disease and hyperplastic polyps referred to Beth Israel Deaconess Medical Center meeting the World Health Organization (WHO) criteria for SPS were identified. RESULTS: Four patients with long standing IBD involving the colon were identified. All of these patients' IBD were in clinical remission. Additionally, 2 of the 4 patients were also noted to have sporadic adenomas. Each patient was also found to have multiple sessile serrated adenomas and hyperplastic polyps meeting the WHO criteria for SPS. Two of the patients had colonoscopy with chromoendoscopy which improved polyp detection. Discussions were held with each patient regarding the potentially increased risk of colorectal cancer with the combination of IBD and SPS. Patients were advised that colectomy would be the safest method to reduce the risk of cancer. None of the patients opted for colectomy and instead planned on a repeat colonoscopy with chromoendoscopy at 3-12 month intervals. CONCLUSION: Serrated polyposis syndrome develops in patients with IBD. It is unclear how high the risk of colon cancer is in patients who have both IBD and SPS and what the recommendations should be regarding the frequency of surveillance or surgery. Further studies are necessary to identify the optimal management of these patients.

Contribution of epithelial plasticity to renal transplantation-associated fibrosis.

Every year in the United States, 5000 renal transplant recipients start or restart dialysis because of the unusual propensity of these allografts to develop interstitial fibrosis and tubular atrophy (IF/TA). Although IF/TA often follows one or more identifiable events, our capacity to specifically treat, prevent, or even detect IF/TA at an early stage is poor. These limitations are largely related to our lack of adequate tools to assess graft failure over time. Data accumulated over the past 5 years have demonstrated that tubular epithelial cells may react to certain fibrogenic stimuli to engage in the process of epithelial-to-mesenchymal transition (EMT). In this review, we highlight the current view of EMT with a focus on both its role in the context of renal transplantation and the potential for utilizing markers of EMT to identify patients undergoing early IF/TA.

Evidence for a circulating islet cell growth factor in insulin-resistant states.

Insulin resistance is a feature of many common disorders including obesity and type 2 diabetes mellitus. In these disorders, the beta-cells compensate for the insulin resistance for long periods of time with an increase in secretory capacity, an increase in beta-cell mass, or both. To determine whether the beta-cell response might relate to a circulating growth factor, we have transplanted normal islets under the kidney capsule of normoglycemic insulin-resistant mice with two different models of insulin resistance: lean mice that have a double heterozygous deletion of the insulin receptor and insulin receptor substrate-1 (DH) or the obese, hyperglycemic ob/ob mice. In the grafts transplanted into both hosts, there was a marked increase in beta-cell mitotic activity and islet mass that was comparable with that observed in the endogenous pancreas. By contrast, islets of the DH mouse transplanted into normal mice showed reduced mitotic index. These data suggest the insulin resistance is associated with a circulating islet cell growth factor that is independent of glucose and obesity.

Altered function of insulin receptor substrate-1-deficient mouse islets and cultured beta-cell lines.

Insulin receptor substrate-1 (IRS-1) is pivotal in mediating the actions of insulin and growth factors in most tissues of the body, but its role in insulin-producing beta islet cells is unclear. Freshly isolated islets from IRS-1 knockout mice and SV40-transformed IRS-1-deficient beta-cell lines exhibit marked insulin secretory defects in response to glucose and arginine. Furthermore, insulin expression is reduced by about 2-fold in the IRS-1-null islets and beta-cell lines, and this defect can be partially restored by transfecting the cells with IRS-1. These data provide evidence for an important role of IRS-1 in islet function and provide a novel functional link between the insulin signaling and insulin secretion pathways. This article may have been published online in advance of the print edition. The date of publication is available from the JCI website, http://www.jci.org.

Leptin accelerates the onset of puberty in normal female mice.

The fat-derived hormone, leptin, is proposed to serve as an adipostatic signal to the brain to reduce food intake and body weight. In addition to its effects on body weight, chronic leptin treatment restores puberty and fertility to ob/ob mice with total leptin deficiency, and acute treatment substantially corrects hypogonadism in mice starved for 2 d without affecting body weight. Leptin may therefore be a critical signal, linking adiposity and reproduction. Since body weight and adiposity appear to play a critical role in the timing of puberty in humans and rodents, and leptin levels rise with increasing adiposity, we studied the effects of once daily injections of recombinant leptin on the onset of puberty in female mice weaned on day 21 and fed ad libitum. There was a linear increase in body weight during the study period, which was not altered by the dose of leptin used. Mice injected with leptin had an earlier onset of three classic pubertal parameters (i.e., vaginal opening, estrus, and cycling) compared with saline-injected controls. Leptin is the first peripheral molecule demonstrated to accelerate the maturation of the reproductive axis in normal rodents. We propose that leptin is the signal that informs the brain that energy stores are sufficient to support the high energy demands of reproduction, and may be a major determinant of the timing of puberty.