Inhibitory effect against polymerase and ribonuclease activities of HIV-reverse transcriptase of the aqueous leaf extract of Terminalia triflora

Dichloromethane, methanol and aqueous extracts from the leaves of Terminalia triflora were investigated for their inhibitory effect on polymerase and ribonuclease activities of HIV reverse transcriptase.The most potent activity was found in the aqueous extract, which inhibited both polymerase and ribonuclease activities of the enzyme with an IC50 of 1.6 micro g/mL and 1.8 micro g/mL respectively. The antiinfective activity of the extract was demonstrated in HLT4LacZ-IIIB cell culture with an IC50 of 1.0 micro g/mL. The extract was submitted to a purification process by extractive and chromatographic methods. The activity remained in the hydrophillic fraction. Tannins present in this active purified fraction, as determined by TLC and HPLC methods, could account for the anti HIV-RT activity found in the aqueous extract

International consensus conference on stool banking for faecal microbiota transplantation in clinical practice

Although faecal microbiota transplantation (FMT) has a well-established role in the treatment of recurrent Clostridioides difficile infection (CDI), its widespread dissemination is limited by several obstacles, including lack of dedicated centres, difficulties with donor recruitment and complexities related to regulation and safety monitoring. Given the considerable burden of CDI on global healthcare systems, FMT should be widely available to most centres. Stool banks may guarantee reliable, timely and equitable access to FMT for patients and a traceable workflow that ensures safety and quality of procedures. In this consensus project, FMT experts from Europe, North America and Australia gathered and released statements on the following issues related to the stool banking: general principles, objectives and organisation of the stool bank; selection and screening of donors; collection, preparation and storage of faeces; services and clients; registries, monitoring of outcomes and ethical issues; and the evolving role of FMT in clinical practice, Consensus on each statement was achieved through a Delphi process and then in a plenary face-to-face meeting. For each key issue, the best available evidence was assessed, with the aim of providing guidance for the development of stool banks in order to promote accessibility to FMT in clinical practice.Peer reviewe

Autologous Haematopoietic Stem Cell Transplantation for Crohn's Disease: A Retrospective Survey of Long-term Outcomes From the European Society for Blood and Marrow Transplantation

Background and Aims: Autologous haematopoietic stem cell transplantation [AHSCT] is a therapeutic option for patients with severe, treatment-refractory Crohn’s disease [CD]. The evidence base for AHSCT for CD is limited, with one randomised trial [ASTIC] suggesting benefit. The aim of this study was to evaluate safety and efficacy for patients undergoing AHSCT for CD in Europe, outside the ASTIC trial. Methods: We identified 99 patients in the European Society for Blood and Marrow Transplantation [EBMT] registry, who were eligible for inclusion. Transplant and clinical outcomes were obtained for 82 patients from 19 centres in seven countries. Results: Median patient age was 30 years [range 20–65]. Patients had failed or been intolerant to a median of six lines of drug therapy; 61/82 [74%] had had surgery. Following AHSCT, 53/78 [68%] experienced complete remission or significant improvement in symptoms at a median follow-up of 41 months [range 6–174]; 22/82 [27%] required no medical therapy at any point post-AHSCT. In patients who had re-started medical therapy at latest follow-up, 57% [24/42] achieved remission or significant symptomatic improvement with therapies to which they had previously lost response or been non-responsive. Treatment-free survival at 1 year was 54%. On multivariate analysis, perianal disease was associated with adverse treatment-free survival (hazard ratio 2.34, 95% confidence interval [CI] 1.14–4.83, p = 0.02). One patient died due to infectious complications [cytomegalovirus disease] at Day +56. Conclusions: In this multicentre retrospective analysis of European centres, AHSCT was relatively safe and appeared to be effective in controlling otherwise treatment-resistant Crohn’s disease. Further prospective randomised controlled trials against standard of care are warranted

Liver function test results predict nutritional status evaluated by arm anthropometric indicators

OBJECTIVES: To compare the anthropometric indicators based on weight and height with the anthropometric indicators based on arm measurements and to predict the anthropometric nutritional status with liver function tests (LFTs) in children with chronic liver disease (CLD). PATIENTS AND METHODS: A cross-sectional study in a referral pediatric hospital enrolled 79 children with CLD (mean age 72.6 � 61.8 months, 54% female). An independent variable of LFT was used to determine the outcome variable of nutritional status. Anthropometric indicators of height versus age, weight versus height, head circumference versus age, and arm indicators versus age were analyzed with Pearson correlation, the determination coefficient r, and multiple regression. RESULTS: A total of 44.3% of patients studied had growth impairment. The anthropomorphic indicator of weight for height identified malnutrition in 11.4%, compared with 43% identified by mid- to upper arm circumference (MUAC) and 40.5% identified with total arm area. MUAC (P < 0.001), total arm circumference (P < 0.001), arm muscle area (P = 0.009), and arm fat area (P = 0.023) identified more cases of z score less than -2 SD than weight/height. The presence of ascites misled weight-for-height measurements. Conjugated bilirubin and albumin had significant correlations with almost all of the anthropometric indicators. Alkaline phosphatase correlated significantly with all of the arm anthropometric indicators. A regression analysis led to 7 prediction models; the highest prediction of z score less than -2 SD was with triceps skinfold and conjugated bilirubin, albumin, and ?-glutamyltransferase; height-for-age z score less than -2 SD was predicted by measurements of conjugated bilirubin, prothrombin time, and alanine aminotransferase. CONCLUSIONS: The data presented underline the correlation between the liver damage severity evaluated by LFT and the nutritional status estimated by anthropometric indicators. In our view these observations reflect the close relationship between liver function and the degree of liver damage to growth and current nutritional status. � 2007 Lippincott Williams & Wilkins, Inc

Long-term outcome of patients with steroid-refractory acute severe UC treated with ciclosporin or infliximab.

OBJECTIVE: Ciclosporin and infliximab have demonstrated short-term similar efficacy as second-line therapies in patients with acute severe UC (ASUC) refractory to intravenous steroids. The aim of this study was to assess long-term outcome of patients included in a randomised trial comparing ciclosporin and infliximab. DESIGN: Between 2007 and 2010, 115 patients with steroid-refractory ASUC were randomised in 29 European centres to receive ciclosporin or infliximab in association with azathioprine. Patients were followed until death or last news up to January 2015. Colectomy-free survival rates at 1 and 5 years and changes in therapy were estimated through Kaplan-Meier method and compared between initial treatment groups through log-rank test. RESULTS: After a median follow-up of 5.4 years, colectomy-free survival rates (95% CI) at 1 and 5 years were, respectively, 70.9% (59.2% to 82.6%) and 61.5% (48.7% to 74.2%) in patients who received ciclosporin and 69.1% (56.9% to 81.3%) and 65.1% (52.4% to 77.8%) in those who received infliximab (p=0.97). Cumulative incidence of first infliximab use at 1 and 5 years in patients initially treated with ciclosporin was, respectively, 45.7% (32.6% to 57.9%) and 57.1% (43.0% to 69.0%). Only four patients from the infliximab group were subsequently switched to ciclosporin. Three patients died during the follow-up, none directly related to UC or its treatment. CONCLUSIONS: In this cohort of patients with steroid-refractory ASUC initially treated by ciclosporin or infliximab, long-term colectomy-free survival was independent from initial treatment. These long-term results further confirm a similar efficacy and good safety profiles of both drugs and do not favour one drug over the other. TRIAL REGISTRATION NUMBER: EudraCT: 2006-005299-42; ClinicalTrials.gouv number: NCT00542152; post-results

Autologous haematopoietic stem cell transplantation for Crohn's disease: a retrospective study from the European Society for Blood &amp; Marrow Transplantation (EBMT) Autoimmune Diseases Working Party

Autologous haematopoietic stem cell transplantation (AHSCT) is an emerging therapeutic option for refractory Crohn’s disease (CD). The ASTIC trial of AHSCT failed to meet its stringent composite primary endpoint, but 1-year follow-up data demonstrate sustained efficacy. The real-world use and outcomes of AHSCT for CD are unknown. Using the EBMT registry, we evaluated long-term outcomes for patients (pts) undergoing AHSCT for CD in Europe

Efficacy and safety of tacrolimus in Crohn's disease: a nationwide, multi-centric study from GETECCU

Background: Crohn's disease (CD) is chronic inflammatory disease of the gastrointestinal tract. Tacrolimus (TCR) is a calcineurin inhibitor drug commonly used for prophylaxis of rejection in renal and liver transplantation. There is some evidence on the short- and medium-term efficacy and safety of TCR in CD, but data are still scarce. The primary aim of our study was to evaluate the efficacy and safety of TCR in CD in clinical practice in Spain. Methods: We performed a retrospective, multi-centric study in 22 inflammatory bowel disease Units in Spain. We included all adult patients with an established diagnosis of CD in whom oral TCR was prescribed for this condition. Clinical response was assessed by Harvey?Bradshaw index (H-B) and physician global assessment after 3 months. Perianal disease was evaluated by fistula drainage assessment (FDA) at the same time point. Follow-up period was considered until the last visit during therapy or 12 months after stopping the drug. Descriptive statistics and non-parametric tests were used in the statistical analysis. Results: Between January 2000 and November 2017 a total of 85 patients received TCR (mean age 36 years; 55% female; 69% perianal disease; mean CRP 14 mg/l). The most common indications for TCR were refractory luminal disease (57%) and perianal disease (32%). Most patients (81%) had previously received at least one anti-TNF agent and 61% ?2. Blood drug levels were 5?10 ng/ml during induction (34%) and maintenance (47%). In 25% of cases, TCR was started concomitantly with systemic steroids, in 11% with an anti-TNF agent and in 6% with vedolizumab. The drug was maintained for a median time of 6 months (2.7?18) and the median follow?up was 28 months (15?56). We found statistically significant differences in H-B after 3 months (median 7.4 (SD 4.4), p = 0.014). FDA showed a complete response in 8%, while 34% had partial response. In the univariate analysis, concomitant thiopurines were significantly associated with short-term clinical response (OR 5.53 95% CI 1.36?22.5, p = 0.017). We observed statistically significant differences in CRP levels 1, 3, 6, and 12 months when compared with baseline (p < 0.03). The drug was stopped in 86% of patients after a median time of 6 months (2?17): 62% requiring a new immunomodulator, 44% hospitalisation and 42% surgery. A total of 34% patients suffered adverse events related to the drug (45% tremor, 28% acute kidney injury), and in 37% they led to the discontinuation of the drug. Conclusions: Tacrolimus shows a clinical benefit in CD in the short-term, but its lower long-term effectiveness and frequent adverse events remain relevant issues in clinical practice

International consensus conference on stool banking for faecal microbiota transplantation in clinical practice

Although faecal microbiota transplantation (FMT) has a well-established role in the treatment of recurrent Clostridioides difficile infection (CDI), its widespread dissemination is limited by several obstacles, including lack of dedicated centres, difficulties with donor recruitment and complexities related to regulation and safety monitoring. Given the considerable burden of CDI on global healthcare systems, FMT should be widely available to most centres. Stool banks may guarantee reliable, timely and equitable access to FMT for patients and a traceable workflow that ensures safety and quality of procedures. In this consensus project, FMT experts from Europe, North America and Australia gathered and released statements on the following issues related to the stool banking: general principles, objectives and organisation of the stool bank; selection and screening of donors; collection, preparation and storage of faeces; services and clients; registries, monitoring of outcomes and ethical issues; and the evolving role of FMT in clinical practice, Consensus on each statement was achieved through a Delphi process and then in a plenary face-to-face meeting. For each key issue, the best available evidence was assessed, with the aim of providing guidance for the development of stool banks in order to promote accessibility to FMT in clinical practice

Long-term outcome of patients with steroid-refractory acute severe UC treated with ciclosporin or infliximab

OBJECTIVE: Ciclosporin and infliximab have demonstrated short-term similar efficacy as second-line therapies in patients with acute severe UC (ASUC) refractory to intravenous steroids. The aim of this study was to assess long-term outcome of patients included in a randomised trial comparing ciclosporin and infliximab. DESIGN: Between 2007 and 2010, 115 patients with steroid-refractory ASUC were randomised in 29 European centres to receive ciclosporin or infliximab in association with azathioprine. Patients were followed until death or last news up to January 2015. Colectomy-free survival rates at 1 and 5 years and changes in therapy were estimated through Kaplan-Meier method and compared between initial treatment groups through log-rank test. RESULTS: After a median follow-up of 5.4 years, colectomy-free survival rates (95% CI) at 1 and 5 years were, respectively, 70.9% (59.2% to 82.6%) and 61.5% (48.7% to 74.2%) in patients who received ciclosporin and 69.1% (56.9% to 81.3%) and 65.1% (52.4% to 77.8%) in those who received infliximab (p=0.97). Cumulative incidence of first infliximab use at 1 and 5 years in patients initially treated with ciclosporin was, respectively, 45.7% (32.6% to 57.9%) and 57.1% (43.0% to 69.0%). Only four patients from the infliximab group were subsequently switched to ciclosporin. Three patients died during the follow-up, none directly related to UC or its treatment. CONCLUSIONS: In this cohort of patients with steroid-refractory ASUC initially treated by ciclosporin or infliximab, long-term colectomy-free survival was independent from initial treatment. These long-term results further confirm a similar efficacy and good safety profiles of both drugs and do not favour one drug over the other. TRIAL REGISTRATION NUMBER: EudraCT: 2006-005299-42; ClinicalTrials.gouv number: NCT00542152; post-results.status: publishe