Transcript levels of Toll-Like receptors 5, 8 and 9 correlate with inflammatory activity in Ulcerative Colitis

<p>Abstract</p> <p>Background</p> <p>Dysregulation of innate immune response by Toll-Like Receptors (TLRs) is a key feature in Ulcerative Colitis (UC). Most studies have focused on <it>TLR2, TLR3</it>, and <it>TLR4 </it>participation in UC. However, few studies have explored other TLRs. Therefore, the aim of this study was to evaluate the mRNA profiles of <it>TLR1 to 9 </it>in colonic mucosa of UC patients, according to disease activity.</p> <p>Methods</p> <p>Colonic biopsies were taken from colon during colonoscopy in 51 patients with Ulcerative Colitis and 36 healthy controls. mRNA levels of <it>TLR1 to 9, Tollip</it>, inflammatory cytokines <it>IL6 </it>and <it>TNF </it>were assessed by RT-qPCR with hydrolysis probes. Characterization of <it>TLR9 </it>protein expression was performed by Immunohistochemistry.</p> <p>Results</p> <p>Toll-like receptors <it>TLR8, TLR9</it>, and <it>IL6 </it>mRNA levels were significantly higher in the colonic mucosa from UC patients (both quiescent and active) as compared to healthy individuals (p < 0.04). In the UC patients group the <it>TLR2, TLR4, TLR8 </it>and <it>TLR9 </it>mRNA levels were found to be significantly lower in patients with quiescent disease, as compared to those with active disease (p < 0.05), whereas <it>TLR5 </it>showed a trend (p = 0.06). <it>IL6 </it>and <it>TNF </it>mRNA levels were significantly higher in the presence of active disease and help to discriminate between quiescent and active disease (p < 0.05). Also, <it>IL6 </it>and <it>TNF </it>mRNA positively correlate with TLRs mRNA with the exception for <it>TLR3</it>, with stronger correlations for <it>TLR5, TLR8</it>, and <it>TLR9 </it>(p < 0.0001). <it>TLR9 </it>protein expression was mainly in the lamina propria infiltrate.</p> <p>Conclusions</p> <p>This study demonstrates that <it>TLR2, TLR4, TLR8</it>, and <it>TLR9 </it>expression increases in active UC patients, and that the mRNA levels positively correlate with the severity of intestinal inflammation as well as with inflammatory cytokines.</p

Detection of epithelial apoptosis in pelvic ileal pouches for ulcerative colitis and familial adenomatous polyposis

<p>Abstract</p> <p>Background</p> <p>Ileal pouch-anal anastomosis (IPAA) is the surgical procedure of choice for patients with refractory ulcerative colitis (UC) and for familial adenomatous polyposis (FAP) with many rectal polyps. Pouchitis is one of the more frequent complications after IPAA in UC patients; however, it is rare in FAP.</p> <p>Objective</p> <p>Evaluate pro-apoptotic activity in endoscopically and histological normal mucosa of the ileal pouch in patients with UC and FAP.</p> <p>Methods</p> <p>Eighteen patients (nine with UC and nine with FAP) with J pouch after total rectocolectomy were studied. Biopsies were obtained from the mucosa of the pouch and from normal ileum. The specimens were snap-frozen and the expressions of Bax and Bcl-2 were determined by immunoblot of protein extracts and by immunohistochemistry analysis. FADD, Caspase-8, APAF-1 and Caspase-9 were evaluated by immunoprecipitation and immunoblot.</p> <p>Results</p> <p>Patients with UC had significantly higher protein levels of Bax and APAF-1, Caspase-9 than patients with FAP, but were similar to controls. The expressions of Bcl-2 and FADD, Caspase-8 were similar in the groups. Immunohistochemistry for Bax showed less intensity of immunoreactions in FAP than in UC and Controls. Bcl-2 immunostaining was similar among the groups.</p> <p>Conclusion</p> <p>Patients with FAP present lower levels of pro-apoptotic proteins in all methods applied, even in the absence of clinical and endoscopic pouchitis and dysplasia in the histological analysis. These findings may explain a tendency of up-regulation of apoptosis in UC patients, resulting in higher rates of progression to pouchitis in these patients, which could correlate with mucosal atrophy that occurs in inflamed tissue. However, FAP patients had low pro-apoptotic activity in the mucosa, and it could explain the tendency to low cell turn over and presence of adenomas in this syndrome.</p

Update of complications and functional outcome of the ileo-pouch anal anastomosis: overview of evidence and meta-analysis of 96 observational studies

Item does not contain fulltextOBJECTIVE: The objective of this study is to provide a comprehensive update of the outcome of the ileo-pouch anal anastomosis (IPAA). DATA SOURCES: An extensive search in PubMed, EMBASE, and The Cochrane Library was conducted. STUDY SELECTION AND DATA EXTRACTION: All studies published after 2000 reporting on complications or functional outcome after a primary open IPAA procedure for UC or FAP were selected. Study characteristics, functional outcome, and complications were extracted. DATA SYNTHESIS: A review with similar methodology conducted 10 years earlier was used to evaluate developments in outcome over time. Pooled estimates were compared using a random-effects logistic meta-analyzing technique. Analyses focusing on the effect of time of study conductance, centralization, and variation in surgical techniques were performed. RESULTS: Fifty-three studies including 14,966 patients were included. Pooled rates of pouch failure and pelvic sepsis were 4.3% (95% CI, 3.5-6.3) and 7.5% (95% CI 6.1-9.1), respectively. Compared to studies published before 2000, a reduction of 2.5% was observed in the pouch failure rate (p = 0.0038). Analysis on the effect of the time of study conductance confirmed a decline in pouch failure. Functional outcome remained stable over time, with a 24-h defecation frequency of 5.9 (95% CI, 5.0-6.9). Technical surgery aspects did not have an important effect on outcome. CONCLUSION: This review provides up to date outcome estimates of the IPAA procedure that can be useful as reference values for practice and research. It is also shows a reduction in pouch failure over time.1 juli 201

Home parenteral nutrition-associated thromboembolic and bleeding events: results of a cohort study of 236 individuals

Essentials Sparse or outdated studies focus on thrombotic and bleeding risk in home parenteral nutrition (HPN). 236 HPN patients followed at a single center for a total of 684 patient-years were evaluated. Rates of venous thrombosis and major bleeding, and prevalence of vena cava syndrome are provided. Anticoagulants might reduce thrombosis risk, but population-specific safety concerns remain. Background Home parenteral nutrition (HPN) is necessary for patients with intestinal failure. Recurrent catheter-related thrombosis (CRT) is common, leading to infectious complications, pulmonary embolism, vascular access loss and intestinal transplantation. The efficacy and safety of anticoagulants are unknown in this setting and based on sparse and low-quality observational data. Objectives Our aim was to estimate the incidence of thromboembolic, bleeding and anticoagulant-related complications in HPN patients, and evaluate risk factors for first venous thrombosis (VT). Methods This retrospective cohort study included all adult patients followed for long-term HPN at our center between 1986 and 2014. Primary outcomes were symptomatic objectively diagnosed VT, encompassing CRT and venous thromboembolism, and major bleeding. Secondary outcomes were vena cava syndrome and heparin-induced thrombocytopenia or hypersensitivity. Results A total of 236 patients were included (median HPN duration, 17 months) and 136 received anticoagulants at HPN onset (57.6%). Overall, the annual incidence of first VT was 11.4% (95% confidence interval [95% CI], 8.6-14.7%); VT was associated with a personal history of thrombosis (adjusted hazard ratio, 2.22; 95% CI, 1.06-4.64), whereas anticoagulation seemed to account only for a mild protection (adjusted hazard ratio, 0.72; 95% CI, 0.36-1.44). The annual incidence of major bleeding was 4.3% for patients on anticoagulants vs. 1.8% for those off anticoagulants. Vena cava syndrome developed in 20.7% of patients with VT. One patient had isolated heparin-induced thrombocytopenia (0.6%) and four had heparin hypersensitivity (2.5%). Conclusions Patients on HPN have a significant risk of venous thrombosis, major bleeding and vena cava syndrome. Anticoagulants might reduce thrombosis risk, but population-specific safety concerns remai

Internet-based behavioural activation therapy versus online psychoeducation for self-reported suicidal ideation in individuals with depression in Indonesia: a secondary analysis of an RCT

Background Southeast Asia has the highest suicide mortality worldwide. To improve our knowledge on the effectiveness of interventions for suicidal ideation (SI) in individuals with depression in Indonesia, we conducted a secondary analysis of a randomised controlled trial.Objective We explored whether an internet-based behavioural activation (BA) intervention (‘Guided Act and Feel Indonesia’ (GAF-ID)) was superior in targeting SI compared with online-delivered psychoeducation (PE).Methods In total, 313 participants were randomised between treatment allocation. The SI item of the Patient Health Questionnaire-9 was the primary outcome measure. Mediation analyses were conducted to identify if BA at week 10 mediated the relationship between intervention and SI at week 24.Findings The GAF-ID intervention was not superior in reducing SI compared with online minimal PE at week 10 (OR 0.61, 95% CI (0.37 to 1.01)), nor at week 24 (OR 0.84, 95% CI (0.47 to 1.52)). SI at week 24 was not mediated by BA at week 10 (b=−0.03, 95% CI (−0.05 to 0.00), p=0.07).Conclusions In individuals with depression in Indonesia, the GAF-ID intervention was not superior in reducing self-reported SI compared with PE. Also, the association between treatment condition and SI at week 24 was not mediated via BA at week 10.Clinical implications This study supports the need for further research on the efficacy of psychological treatments targeting SI in the Southeast Asia context

Suicidal ideation in remitted major depressive disorder predicts recurrence

Introduction: Each year almost 800.000 people die from suicide, of which up to 87% are affected by major depressive disorder (MDD). Despite the strong association between suicidality and MDD, it remains unknown if suicidal symptoms during remission put remitted recurrent MDD patients (rrMDD) at risk for recurrence. Methods: At baseline we compared sociodemographic characteristics and suicidal symptoms in un-medicated rrMDD participants to matched never-depressed controls. We used the HDRS17 and IDS-SR30 to assess suicidal symptoms and depressive symptomatology. Next, we studied the longitudinal association between baseline suicidal symptoms and time to recurrence(s) in rrMDD during a 2.5-year follow-up period using cox regression analyses. Further, we studied with longitudinal data whether suicidal symptoms and depressive symptomatology were cross-sectionally associated using mixed model analysis. Results: At baseline, rrMDD participants (N = 73) had higher self-reported suicidal symptoms than matched never-depressed controls (N = 45) (χ2 = 12.09 p <.002). Self-reported suicidal symptoms were almost four times higher (27.9% versus 6.9%) compared to clinician-rated suicidal symptoms in rrMDD at baseline. Self-reported baseline suicidal symptoms, but not clinician-rated symptoms, predicted earlier MDD-recurrence during follow-up, independent of other residual depressive symptoms (χ2 = 7.26, p <.026). Higher suicidal symptoms were longitudinally related to higher depressive symptoms (HDRS17; F = 49.87, p <.001), IDS-SR30; (F = 22.36, p <.001). Conclusion: This study showed that self-reported – but not clinician-rated - suicidal symptoms persist during remission in rrMDD and predict recurrence, independent from residual symptoms. We recommend to monitor both suicidal and depressive symptomatology during remission in rrMDD, preferably also including self-reported questionnaires apart from clinician-rated. It would be beneficial for future research to assess suicidality using questionnaires primarily designed for measuring suicidal ideation

Perceived ethnic discrimination, suicidal ideation and mastery in a multi-ethnic cohort: The HELIUS study

Background The association between perceived ethnic discrimination (PED) and mental health conditions is well studied. However, less is known about the association between PED and suicidal ideation, or the role of positive psychosocial factors in this association. Aims To examine the association between PED and suicidal ideation among ethnic minority groups in Amsterdam, The Netherlands, and investigate whether ethnicity and mastery (people's extent of feeling in control of their lives and environment) moderate this association. Method Cross-sectional data from the multi-ethnic HELIUS study were analysed (n = 17 053) for participants of South-Asian Surinamese, African Surinamese, Ghanaian, Turkish and Moroccan origin. PED was measured using the Everyday Discrimination Scale, suicidal ideation using item 9 of the Patient Health Questionnaire-9 and mastery using the Pearlin-Schooler Mastery Scale. Results Logistic regression analyses demonstrated a small positive association between PED and suicidal ideation (OR = 1.068, 95% CI 1.059-1.077), which did not differ among ethnic minority groups. Mastery did not moderate the association between PED and suicidal ideation among the ethnic minority groups. Conclusions Our findings support the hypothesis that PED is associated with suicidal ideation and this association does not significantly vary between ethnic minority groups. Although higher levels of mastery were associated with lower suicidal ideation, mastery did not moderate the relationship between PED and suicidal ideation. Besides targeting ethnic discrimination as a societal problem, future longitudinal research is needed to investigate whether interventions aimed at improving mastery could reduce suicidal ideation in ethnic minority groups