Probiotic prophylaxis in patients with predicted severe acute pancreatitis (PROPATRIA): design and rationale of a double-blind, placebo-controlled randomised multicenter trial [ISRCTN38327949]

BACKGROUND: Infectious complications are the major cause of death in acute pancreatitis. Small bowel bacterial overgrowth and subsequent bacterial translocation are held responsible for the vast majority of these infections. Goal of this study is to determine whether selected probiotics are capable of preventing infectious complications without the disadvantages of antibiotic prophylaxis; antibiotic resistance and fungal overgrowth. METHODS/DESIGN: PROPATRIA is a double-blind, placebo-controlled randomised multicenter trial in which 200 patients will be randomly allocated to a multispecies probiotic preparation (Ecologic 641) or placebo. The study is performed in all 8 Dutch University Hospitals and 7 non-University hospitals. The study-product is administered twice daily through a nasojejunal tube for 28 days or until discharge. Patients eligible for randomisation are adult patients with a first onset of predicted severe acute pancreatitis: Imrie criteria 3 or more, CRP 150 mg/L or more, APACHE II score 8 or more. Exclusion criteria are post-ERCP pancreatitis, malignancy, infection/sepsis caused by a second disease, intra-operative diagnosis of pancreatitis and use of probiotics during the study. Administration of the study product is started within 72 hours after onset of abdominal pain. The primary endpoint is the total number of infectious complications. Secondary endpoints are mortality, necrosectomy, antibiotic resistance, hospital stay and adverse events. To demonstrate that probiotic prophylaxis reduces the proportion of patients with infectious complications from 50% to 30%, with alpha 0,05 and power 80%, a total sample size of 200 patients was calculated. CONCLUSION: The PROPATRIA study is aimed to show a reduction in infectious complications due to early enteral use of multispecies probiotics in severe acute pancreatitis

Pancreatitis, very early compared with normal start of enteral feeding (PYTHON trial): design and rationale of a randomised controlled multicenter trial

Contains fulltext : 97199.pdf (publisher's version ) (Open Access)BACKGROUND: In predicted severe acute pancreatitis, infections have a negative effect on clinical outcome. A start of enteral nutrition (EN) within 24 hours of onset may reduce the number of infections as compared to the current practice of starting an oral diet and EN if necessary at 3-4 days after admission. METHODS/DESIGN: The PYTHON trial is a randomised controlled, parallel-group, superiority multicenter trial. Patients with predicted severe acute pancreatitis (Imrie-score >/= 3 or APACHE-II score >/= 8 or CRP > 150 mg/L) will be randomised to EN within 24 hours or an oral diet and EN if necessary, after 72 hours after hospital admission.During a 3-year period, 208 patients will be enrolled from 20 hospitals of the Dutch Pancreatitis Study Group. The primary endpoint is a composite of mortality or infections (bacteraemia, infected pancreatic or peripancreatic necrosis, pneumonia) during hospital stay or within 6 months following randomisation. Secondary endpoints include other major morbidity (e.g. new onset organ failure, need for intervention), intolerance of enteral feeding and total costs from a societal perspective. DISCUSSION: The PYTHON trial is designed to show that a very early (< 24 h) start of EN reduces the combined endpoint of mortality or infections as compared to the current practice of an oral diet and EN if necessary at around 72 hours after admission for predicted severe acute pancreatitis. TRIAL REGISTRATION: ISRCTN: ISRCTN18170985

Mangafodipir Protects against Hepatic Ischemia-Reperfusion Injury in Mice

Mangafodipir is a contrast agent used in magnetic resonance imaging that concentrates in the liver and displays pleiotropic antioxidant properties. Since reactive oxygen species are involved in ischemia-reperfusion damages, we hypothesized that the use of mangafodipir could prevent liver lesions in a mouse model of hepatic ischemia reperfusion injury. Mangafodipir (MnDPDP) was compared to ischemic preconditioning and intermittent inflow occlusion for the prevention of hepatic ischemia-reperfusion injury in the mouse.Mice were subjected to 70% hepatic ischemia (continuous ischemia) for 90 min. Thirty minutes before the ischemic period, either mangafodipir (10 mg/kg) or saline was injected intraperitoneally. Those experimental groups were compared with one group of mice preconditioned by 10 minutes' ischemia followed by 15 minutes' reperfusion, and one group with intermittent inflow occlusion. Hepatic ischemia-reperfusion injury was evaluated by measurement of serum levels of aspartate aminotransferase (ASAT) activity, histologic analysis of the livers, and determination of hepatocyte apoptosis (cytochrome c release, caspase 3 activity). The effect of mangafodipir on the survival rate of mice was studied in a model of total hepatic ischemia.<0.01), and by higher rates of survival in treated than in untreated animals (P<0.001). The level of protection by mangafodipir was similar to that observed following intermittent inflow occlusion and higher than after ischemic preconditioning.Mangafodipir is a potential new preventive treatment for hepatic ischemia-reperfusion injury

Prevention of postoperative recurrence of Crohn's disease.

BACKGROUND: Up to 75% of patients with Crohn's disease (CD) will have intestinal resection during their life. Most patients will, however, develop postoperative recurrence (endoscopic, clinical or surgical). Several medical and surgical strategies have been attempted to prevent postoperative recurrence. This review evaluates the efficacy of different drug regimens and surgical techniques in the prevention of clinical, endoscopic and surgical postoperative recurrence of CD. METHODS: A literature search for randomized controlled trials on medical or surgical interventions was performed. The endpoints for efficacy were clinical, endoscopic and surgical recurrence. Meta-analyses were performed in case two or more RCTs evaluated the same drug or surgical technique. RESULTS: Mesalamine is more effective in preventing clinical recurrence than placebo (P=0,012), as well as nitroimidazolic antibiotics at one year follow-up (P&lt;0.001) and thiopurines (P=0.018). Nitroimidazolic antibiotics are also more effective than placebo in preventing endoscopic recurrence (P=0.037), as well as thiopurines (P=0.015) and infliximab (P=0.006). Budenoside, probiotics, Interleukin-10 nor any of the different surgical procedures showed any significant difference compared to placebo in postoperative recurrence rates of CD. CONCLUSION: Among the different drug regimens and surgical techniques, only thiopurines and nitroimidazolic antibiotics are able to reduce postoperative clinical as well as endoscopic recurrence of CD. Mesalamine and infliximab also seem to be superior to placebo in preventing clinical recurrence and endoscopic recurrence, respectively. There is a paucity of trials evaluating long-term follow-up and prevention of surgical recurrence of CD

Small bowel preservation for intestinal transplantation: a review.

Intestinal transplantation has become the therapy of choice for patients with intestinal failure and life-threatening complications from total parenteral nutrition. Results, however, remain inferior as compared with other transplant types with the quality of the organ graft as the most important factor of outcome after transplantation. The intestine is extremely sensitive to ischemia. Unfortunately, a relatively long ischemic preservation period is inevitable. The current standard in organ preservation [cold storage (CS) with University of Wisconsin solution] was developed for kidney/liver preservation and is suboptimal for the intestinal graft despite good results for other organs. This review aimed at appraising the results from the use of previously applied and recently developed preservation solutions and techniques to identify key areas for improvement. As the studies available do not reveal the most effective method for intestinal preservation, an optimal strategy will result from a synergistic effect of different vital elements identified from a review of published material from the literature. A key factor is the composition of the solution using a low-viscosity solution to facilitate washout of blood, including amino acids to improve viability, impermeants and colloids to prevent edema, and buffer for pH-homeostasis. Optimizing conditions include a vascular flush before CS and luminal preservation. The most effective composition of the luminal solution and a practical, clinically applicable optimal technique are yet to reach finality. Short-duration oxygenated arterial and/or luminal perfusion have to be considered. Thus, a tailor-made approach to luminal preservation solution and technique need further investigation in transplant models and the human setting to develop the ultimate technique meeting the physiologic demands of the intestinal graft during preservation

Propofol-based anaesthesia versus sevoflurane-based anaesthesia for living donor kidney transplantation: results of the VAPOR-1 randomized controlled trial

Background Kidney transplantation is associated with harmful processes affecting the viability of the graft. One of these processes is associated with the phenomenon of ischaemia–reperfusion injury. Anaesthetic conditioning is a widely described strategy to attenuate ischaemia–reperfusion injury. We therefore conducted the Volatile Anaesthetic Protection of Renal Transplants-1 trial, a pilot project evaluating the influence of two anaesthetic regimens, propofol- vs sevoflurane-based anaesthesia, on biochemical and clinical outcomes in living donor kidney transplantation. Methods Sixty couples were randomly assigned to the following three groups: PROP (donor and recipient propofol), SEVO (donor and recipient sevoflurane), and PROSE (donor propofol and recipient sevoflurane). The primary outcome was renal injury reflected by urinary biomarkers. The follow-up period was 2 yr. Results Three couples were excluded, leaving 57 couples for analysis. Concentrations of kidney injury molecule-1 (KIM-1), N-acetyl-β-d-glucosaminidase (NAG), and heart-type fatty acid binding protein (H-FABP) in the first urine upon reperfusion showed no differences. On day 2, KIM-1 concentrations were higher in SEVO [952.8 (interquartile range 311.8–1893.0) pg mmol−1] compared with PROP [301.2 (202.0–504.7) pg mmol−1]. This was the same for NAG: SEVO, 1.835 (1.162–2.457) IU mmol−1vs PROP, 1.078 (0.819–1.713) IU mmol−1. Concentrations of H-FABP showed no differences. Measured glomerular filtration rate at 3, 6, and 12 months showed no difference. After 2 yr, there was a difference in the acute rejection rate (P=0.039). Post hoc testing revealed a difference between PROP (35%) and PROSE (5%; P=0.020). The difference between PROP and SEVO (11%) was not significant (P=0.110). Conclusions The SEVO group showed higher urinary KIM-1 and NAG concentrations in living donor kidney transplantation on the second day after transplantation. This was not reflected in inferior graft outcome. Clinical trial registration NCT01248871.</p

Propofol-based anaesthesia versus sevoflurane-based anaesthesia for living donor kidney transplantation : results of the VAPOR-1 randomized controlled trial

Background. Kidney transplantation is associated with harmful processes affecting the viability of the graft. One of these processes is associated with the phenomenon of ischaemia-reperfusion injury. Anaesthetic conditioning is a widely described strategy to attenuate ischaemia-reperfusion injury. We therefore conducted the Volatile Anaesthetic Protection of Renal Transplants-1 trial, a pilot project evaluating the influence of two anaesthetic regimens, propofol-vs sevoflurane-based anaesthesia, on biochemical and clinical outcomes in living donor kidney transplantation. Methods. Sixty couples were randomly assigned to the following three groups: PROP (donor and recipient propofol), SEVO (donor and recipient sevoflurane), and PROSE (donor propofol and recipient sevoflurane). The primary outcome was renal injury reflected by urinary biomarkers. The follow-up period was 2 yr. Results. Three couples were excluded, leaving 57 couples for analysis. Concentrations of kidney injury molecule-1 (KIM-1), N-acetyl-beta-D-glucosaminidase (NAG), and heart-type fatty acid binding protein (H-FABP) in the first urine upon reperfusion showed no differences. On day 2, KIM-1 concentrations were higher in SEVO [952.8 (interquartile range 311.8-1893.0) pg mmol(-1)] compared with PROP [301.2 (202.0-504.7) pg mmol(-1)]. This was the same for NAG: SEVO, 1.835 (1.162-2.457) IU mmol(-1) vs PROP, 1.078 (0.819-1.713) IU mmol(-1). Concentrations of H-FABP showed no differences. Measured glomerular filtration rate at 3, 6, and 12 months showed no difference. After 2 yr, there was a difference in the acute rejection rate (P = 0.039). Post hoc testing revealed a difference between PROP (35%) and PROSE (5%; P = 0.020). The difference between PROP and SEVO (11%) was not significant (P = 0.110). Conclusions. The SEVO group showed higher urinary KIM-1 and NAG concentrations in living donor kidney transplantation on the second day after transplantation. This was not reflected in inferior graft outcome