Encapsulating peritoneal sclerosis (EPS) is a life-threatening complication of long-term peritoneal dialysis (PD), which may even occur after patients have switched to hemodialysis (HD) or undergone kidney transplantation. The incidence of EPS varies across the globe and increases with PD vintage. Causative factors are the chronic exposure to bioincompatible PD solutions, which cause long-term modifications of the peritoneum, a high peritoneal transporter status involving high glucose concentrations, peritonitis episodes, and smoldering peritoneal inflammation. Additional potential causes are predisposing genetic factors and some medications. Clinical symptoms comprise signs of intestinal obstruction and a high peritoneal transporter status with incipient ultrafiltration failure. In radiological, macro-, and microscopic studies, a massively fibrotic and calcified peritoneum enclosed the intestine and parietal wall in such cases. Empirical treatments commonly used are corticosteroids and tamoxifen, which has fibrinolytic properties. Immunosuppressants like azathioprine, mycophenolate mofetil, or mTOR inhibitors may also help with reducing inflammation, fibrin deposition, and collagen synthesis and maturation. In animal studies, N-acetylcysteine, colchicine, rosiglitazone, thalidomide, and renin-angiotensin system (RAS) inhibitors yielded promising results. Surgical treatment has mainly been performed in severe cases of intestinal obstruction, with varying results. Mortality rates are still 25–55% in adults and about 14% in children. To reduce the incidence of EPS and improve the outcome of this devastating complication of chronic PD, vigorous consideration of the risk factors, early diagnosis, and timely discontinuation of PD and therapeutic interventions are mandatory, even though these are merely based on empirical evidence.

The disruption of balance between production of reactive oxygen species and antioxidant systems in favor of the oxidants is termed oxidative stress (OS). To counteract the damaging effects of prooxidant free radicals, all aerobic organisms have antioxidant defense mechanisms that are aimed at neutralizing the circulating oxidants and repair the resulting injuries. Antioxidants are either endogenous (the natural defense mechanisms produced by the human body) or exogenous, found in supplements and foods. OS is present at the early stages of chronic kidney disease, augments progressively with renal function deterioration, and is further exacerbated by renal replacement therapy. End-stage renal disease patients, on hemodialysis (HD) or peritoneal dialysis (PD), suffer from accelerated OS, which has been associated with increased risk for mortality and cardiovascular disease. During HD sessions, the bioincompatibility of dialyzers and dialysate trigger activation of white blood cells and formation of free radicals, while a significant loss of antioxidants is also present. In PD, the bioincompatibility of solutions, including high osmolality, elevated lactate levels, low pH, and accumulation of advanced glycation end-products trigger formation of prooxidants, while there is significant loss of vitamins in the ultrafiltrate. A number of exogenous antioxidants have been suggested to ameliorate OS in dialysis patients. Vitamins B, C, D, and E, coenzyme Q10, L-carnitine, a-lipoic acid, curcumin, green tea, flavonoids, polyphenols, omega-3 polyunsaturated fatty acids, statins, trace elements, and N-acetylcysteine have been studied as exogenous antioxidant supplements in both PD and HD patients.

Association between nonalcoholic fatty liver disease and acute ischemic stroke severity and outcome

Barrett's esophagus (BE) is a premalignant condition of the distal esophagus. For diagnostic purposes it is important to find biomarkers that can specifically identify BE, for instance to differentiate BE epithelial cells from gastric cardia epithelial cells in brush cytology specimens. The objective of this study was to determine the specificity of CDX-2 and a set of cytokeratins (CKs) as specific markers for BE as compared with normal squamous esophageal and gastric cardia tissue. Immunohistochemistry (IHC) with specific antibodies against CDX-2, and a set of CKs was performed on fresh frozen consecutive tissue sections of normal squamous, gastric cardia and non-dysplastic BE of 80 patients. IHC results showed CK8, CK18 and CK20 expression in both BE and gastric cardia, while CK7 was seen in all BE but also in 26% of gastric cardia biopsies. CK10/13 was only expressed in normal squamous epithelium. CDX-2 nuclear staining was found in 87.5% of the BE biopsies, whereas normal squamous esophagus and cardia biopsies were negative. CDX-2 in combination with a set of CKs can be used as biomarkers to distinguish between BE and normal squamous esophagus. In order to distinguish BE from cardia tissue, a combination of CDX-2 and CK7 is most informative.

Bile acids may play a role in the pathogenesis of Barrett’s esophagus (BE). Bile composition can be influenced by oral administration of ursodeoxycholic acid (UDCA). We prospectively investigated the effect of proton pump inhibitors (PPI) supplemented with UDCA in vivo in patients with BE. Patients with no or low-grade dysplasia who were clinically asymptomatic on PPI were eligible for the study. In order to exclude the effects of acid reflux, all patients were initially treated with 40 mg esomeprazole (ESO) twice daily for 6 months and continued on this dose till the end of the study (t = 12 months). During a period of 6 months (t = 6 month – t = 12 month) patients were treated with oral UDCA (600 mg twice daily). Patients underwent endoscopy at t = 0 months, t = 6 months and t = 12 months with multiple biopsies of the distal and proximal BE segment, normal squamous and gastric cardia. In addition, pH was measured at t = 0 months and t = 6 months using a BRAVO wireless pH capsule. Bile was sampled at the beginning of the UDCA treatment and 6 months later (t = 6 month and t = 12 month). All biopsies were reviewed for the extent of metaplasia, dysplasia, and acute and chronic inflammation. In addition, proliferation (Ki67), differentiation (villin, cytokeratins 7 and 20) and inflammation (COX-2) were investigated by immunohistochemistry (IHC). Nine patients (mean age 60 years, median BE length 7 cm) were included, of whom six had no dysplasia and three had low-grade dysplasia. pH measurements revealed a normal acid exposure in most patients at t = 0 and t = 6 months. In addition, bile composition analysis demonstrated the efficacy of UDCA. Combining the results of both phases of the study, no significant changes were seen in any of the histological or IHC parameters. Differentiation and proliferation parameters showed no significant changes. In this study, in BE patients who were clinically asymptomatic on PPI, increasing the PPI dose to the maximum for 6 months followed by the addition of UDCA for 6 months did not result in significant histological or IHC changes in their BE.