Low incidence but poor prognosis of complicated coeliac disease: A retrospective multicentre study.

Abstract BACKGROUND: Coeliac disease is a chronic enteropathy characterized by an increased mortality caused by its complications, mainly refractory coeliac disease, small bowel carcinoma and abdominal lymphoma. Aim of the study was to study the epidemiology of complications in patients with coeliac disease. METHODS: Retrospective multicenter case-control study based on collection of clinical and laboratory data. The incidence of complicated coeliac disease was studied among coeliac patients directly diagnosed in four Italian centres. Patients referred to these centres after a diagnosis of coeliac disease and/or complicated coeliac disease in other hospitals were therefore excluded. RESULTS: Between 1/1999 and 10/2011, 1840 adult coeliac patients were followed up for 7364.3 person-years. Fourteen developed complications. Since five patients died, at the end of the observation period (10/2011), the prevalence of complicated coeliac disease was 9/1835 (1/204, 0.49%, 95% CI 0.2-0.9%). The annual incidence of complicated coeliac disease in the study period was 14/7364 (0.2%, 95% CI 0.1-0.31%). Although complications tend to occur soon after the diagnosis of coeliac disease, Kaplan-Meier curve analysis showed that they can actually occur at any time after the diagnosis of coeliac disease. CONCLUSIONS: Complications of coeliac disease in our cohort were quite rare, though characterised by a very high mortality

Therapeutic potential of fetal liver cells transplantation in hemophilia A mice

: Hemophilia A (HA) cell therapy approaches in pediatric individuals require suitable factor (F)VIII-producing cells for stable engraftment. Liver sinusoidal endothelial cells (LSEC) and hematopoietic stem cells (HSC) have been demonstrated to be suitable for the treatment of adult HA-mice. However, after transplantation in busulfan (BU)-conditioned newborn mice, adult LSEC/HSC cannot efficiently engraft, while murine fetal liver (FL) hemato/vascular cells from embryonic day 11-13 of gestation (E11-E13), strongly engraft the hematopoietic and endothelial compartments while also secreting FVIII. Our aim was to investigate the engraftment of FL cells in newborn HA mice for obtaining a suitable "proof of concept" for the development of a new HA treatment in neonates. Hence, we transplanted FLE11 or E13 cells and adult bone marrow (BM) cells into newborn HA mice with or without BU preconditioning. The engraftment levels and FVIII activity was assessed starting from 6 weeks after transplantation. FLE11-E13+BU-transplanted newborns reached up to 95% engraftment with stable FVIII activity levels observed for 16 months. FLE13 cells showed engraftment ability even in absence of BU preconditioning, while FLE11 cells did not. BM+BU transplanted newborn HA mice showed high levels of engraftment; nevertheless, in contrast to FL cells, BM cells cannot engraft HA newborns in non-conditioning regimen. Finally, none of the transplanted mice developed anti-FVIII antibodies. Overall, this study sheds some light on the therapeutic potential of healthy FL cells in the cure of HA neonatal/pediatric patients

Bipolar disorders: is there an influence of seasonality or photoperiod?

Objective: To increase understanding of the influence of photoperiod variation in patients with bipolar disorders. Methods: We followed a sample of Italian bipolar patients over a period of 24 months, focusing on inpatients. All patients admitted to the Psychiatric Inpatient Unit of San Luigi Gonzaga Hospital in Orbassano (Turin, Italy) between September 1, 2013 and August 31, 2015 were recruited. Sociodemographic and clinical data were collected. Results: Seven hundred and thirty patients were included. The admission rate for bipolar patients was significantly higher during May, June and July, when there was maximum sunlight exposure, although no seasonal pattern was found. Patients with (hypo)manic episodes were admitted more frequently during the spring and during longer photoperiods than those with major depressive episodes. Conclusions: Photoperiod is a key element in bipolar disorder, not only as an environmental factor but also as an important clinical parameter that should be considered during treatment

ADVERSE EVENTS OF ANTIPSYCHOTICS AND CYTOCHROME POLYMORPHISMS: A CASE SERIES ON 31 PATIENTS

Background: Adverse events (AEs) contribute to poor outcome in patients affected by mental disorders. The aim of this case series is to describe how many antipsychotics-associated serious AEs could have been prevented if we had known in advance the genetic profile of the patient. Subjects and methods: Data of patients who required the prescription of an antipsychotic drug, with a history of a documented antipsychotics-associated serious AE and who underwent Neuropharst were retrospectively collected. Results: Thirty-three subjects were selected for eligibility; two of them were excluded. Twelve subjects (38.7%) showed genetic polymorphisms most likely associated to an increased risk of AE, with pharmacokinetic variations being the most prevalent. Moreover, the 35.5% of the total sample revealed drug-drug interactions (pharmacodynamic/pharmacokinetic) associated with increased risk of AE. Conclusions: This case series highlights how pharmacogenetics testing with decision support tools, if applied earlier during the treatment with antipsychotics, could have led to identifying individuals at risk for serious AEs

The influence of sunlight exposure on hospitalization in emergency psychiatry

Objective: Environmental conditions during early life may affect individual vulnerability to both physiological changes as well as psychiatric conditions, especially in those with a genetic susceptibility. Among all factors, sunlight exposure intensity has a crucial effect on affecting circadian functions high-risk individuals. A potential explanation of this relation is that excessive sunlight exposure is able to impair biological mechanisms, possibly through the dysregulation of serotonin and/or melatonin production/metabolism. The aim of this study was to evaluate the influence of excessive sunlight exposure in a sample of emergency psychiatry inpatients. Methods: All subjects were consecutively recruited from the Psychiatric Inpatient Unit of San Luigi Gonzaga Hospital, Orbassano (University of Turin, Italy) from September 2013 to August 2015. Socio-demographic and clinical characteristics were carefully collected. Results: We initially screened a sample of 900 patients; however, only 730 subjects voluntary accepted to participate in the study. Patients with admissions in spring/summer (a period in which daylight/darkness ratio is longer) showed a higher prevalence of involuntary admission, an earlier age at illness onset, a longer duration of hospitalization and admission for (hypo)manic episode. Conclusions: Excessive sunlight exposure may exert a fundamental role on psychopathological conditions presumably affecting biological vulnerability. A better understanding of its effect on the course of bipolar and other psychiatric disorders may assist in tailoring the adequate treatment for patients resulting in a shorter stay within hospitalized settings and a better treatment response

Bioavailability of VEGF in Tumor-Shed Vesicles Depends on Vesicle Burst Induced by Acidic pH

Tumor angiogenesis is regulated by a dynamic cross-talk between tumor cells and the host microenvironment. Because membrane vesicles shed by tumor cells are known to mediate several tumor-host interactions, we determined whether vesicles might also stimulate angiogenesis. Vesicles shed by human ovarian carcinoma cell lines CABAI and A2780 stimulated the motility and invasiveness of endothelial cells in vitro. Enzyme-linked immunosorbent assay and Western blot analysis revealed relevant amounts of vascular endothelial growth factor (VEGF) and the two matrix metalloproteinases MMP-2 and MMP-9, but not fibroblast growth factor-2, contained in shed vesicles. An A2780 cell-derived clone transfected to overexpress VEGF shed the same amount of vesicles as did a control clone, but contained significantly more VEGF within the vesicles. Despite a greater amount of VEGF in vesicles of the over-expressing clone, vesicles of both clones stimulated endothelial cell motility to comparable levels, suggesting that VEGF was stored within the vesicle and was unavailable. Only following vesicle burst induced by acidic pH (a characteristic of the tumor microenvironment) was VEGF released, leading to significantly higher stimulation of cell motility. Thus, tumor-shed membrane vesicles carry VEGF and release it in a bioactive form in conditions typical of the tumor microenvironment