Efficacy and Safety of IV albumin for non-spontaneous bacterial peritonitis infection among patients with cirrhosis: A systematic review and meta-analysis
Wong YJ, Qiu TY, Tam YC, Mohan BP, Gallegos-Orozco JF, Adler DG
Dig Liver Dis. 2020
Efficacy and Safety of intravenous albumin for non-spontaneous bacterial peritonitis infection among patients with cirrhosis: A systematic review and meta-analysis of randomized controlled trials INTRODUCTION Bacterial infection is a common cause of acute-on-chronic liver failure (ACLF) and death among cirrhosis. The benefit of intravenous (IV) albumin among cirrhosis with non-SBP infection remains unclear as individual studies are underpowered to detect the survival benefit of IV albumin. AIM: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of intravenous albumin for non-SBP infection among cirrhosis patients. METHODS We performed a systematic search of electronic databases (Pubmed, MEDLINE and Clinicalkey) up to 1(st) December 2019. Studies evaluating IV albumin for non-SBP infection were selected. Using random effect model, the pooled odds ratio (OR), 95% confidence interval (95%CI) and heterogeneity were assessed. RESULTS A total of 3 RCTs (406 subjects) fulfilling the inclusion criteria among 218 citations were identified. There was no significant heterogeneity across included studies. In this meta-analysis, we found that the pooled risk of renal impairment (RI) (OR=0.58, 95%CI: 0.28-1.23, I(2)=0%), mortality at 30 days (OR=1.61, 95%CI: 0.87-3.00, I(2)=0%) as well as mortality at 90 days (OR=1.30, 95%CI: 0.81-2.07, I(2)=0%) were similar between albumin and control group. Pooled event of pulmonary edema occurred more commonly in albumin group (OR 5.17, 95%CI 1.62-16.47, I(2)=0%). More subjects achieved resolution of ACLF in IV albumin group as compared to control group (OR=0.11, 95%CI: 0.02-0.69, p=0.02). CONCLUSION Albumin did not reduce the risk of RI and mortality, yet increases the risk of pulmonary edema. Albumin may promote recovery of ACLF, however, more data is required to validate this benefit.
Strategies to Optimize Anti-tumor Necrosis Factor Therapy for Perianal Fistulizing Crohn's Disease: A Systematic Review
Tandon P, Rhee GG, Schwartz D, McCurdy JD
Digestive diseases and sciences. 2019
Tumor necrosis factor (TNF) antagonists are considered the cornerstone therapy for fistulizing perianal Crohn's disease (PCD), yet a substantial proportion of patients fail to achieve healing. Therefore, we reviewed the evidence for strategies to enhance the efficacy of TNF antagonists for PCD. A systematic search of electronic databases through July 2018 was performed to identify studies that assessed the effectiveness of TNF antagonists combined with another medical or surgical intervention for PCD; or assessed the association between anti-TNF serum concentrations and fistula healing. Twelve studies compared anti-TNF therapy alone versus a combined approach: four with surgery, three with antibiotics, and five with immunomodulators. Only two studies, both with antibiotics, were rated high quality. The addition of antibiotics to anti-TNF therapy resulted in significantly higher rates of fistula response and healing in one study, and a trend toward reduction in fistula drainage in the other. Three of four studies found higher rates of fistula healing when surgery was combined with TNF antagonists. In contrast, one of five studies found a trend toward higher rates of fistula healing in patients treated concomitantly with immunomodulators. Five observational studies assessed the association between anti-TNF concentration and fistula healing. Higher infliximab serum concentrations were consistently associated with fistula healing. In conclusion, few high-quality studies assessing strategies to optimize anti-TNF therapy for PCD exist. Although antibiotics, possibly surgery, and higher serum infliximab concentrations appear to improve fistula healing, future prospective studies are needed to determine the optimal treatment strategy.
Four-factor prothrombin complex concentrate reduces time to procedure in vitamin K antagonist-treated patients experiencing gastrointestinal bleeding: a post hoc analysis of two randomized controlled trials
Refaai MA, Kothari TH, Straub S, Falcon J, Sarode R, Goldstein JN, Brainsky A, Omert L, Lee ML, Milling TJ
Emergency Medicine International. 2017;2017:8024356.
INTRODUCTION To investigate the impact of a 4-factor prothrombin complex concentrate (4F-PCC [Beriplex(R)/Kcentra(R)]) versus plasma on "time to procedure" in patients with acute/severe gastrointestinal bleeding requiring rapid vitamin K antagonist (VKA) reversal prior to invasive procedure. METHODS A post hoc analysis of two phase III trials of 4F-PCC versus plasma in patients with acute/severe gastrointestinal bleeding. The treatment arms were compared for study treatment volume, infusion times, and time from start of study treatment to procedure. RESULTS Analysis included 42 patients (plasma, n = 20; 4F-PCC, n = 22). Median (interquartile range) infusion time was significantly shorter for the 4F-PCC group than for the plasma group (16 [13, 26] min versus 210 [149, 393] min; P < 0.0001). Median infusion volumes were significantly smaller (103 [80, 130] mL versus 870 [748, 1001] mL; P < 0.0001) and median time from study treatment initiation to first procedure was significantly shorter in the 4F-PCC group than in the plasma group (17.5 [12.8, 22.8] versus 23.9 [18.5, 62.0] h; P = 0.037). CONCLUSIONS In this analysis of patients with acute/severe gastrointestinal bleeding requiring urgent VKA reversal prior to an invasive procedure, 4F-PCC (compared with plasma) was associated with smaller infusion volumes, shorter infusion times, and reduced time to procedure.
Fibrin glue is effective healing perianal fistulas in patients with Crohn's disease
Grimaud JC, Munoz-Bongrand N, Siproudhis L, Abramowitz L, Sénéjoux A, Vitton V, Gambiez L, Flourié B, Hébuterne X, Louis E, et al
Gastroenterology. 2010;138((7):):2275-81, 2281.e1.
BACKGROUND & AIMS Fibrin glue is a therapeutic for fistulas that activates thrombin to form a fibrin clot, which mechanically seals the fistula tract. We assessed the efficacy and safety of a heterologous fibrin glue that was injected into the fistula tracts of patients with Crohn's disease (ClinicalTrials. gov No. NCT00723047). METHODS This multicenter, open-label, randomized controlled trial included patients with a Crohn's disease activity index < or =250 and fistulas between the anus (or low rectum) and perineum, vulva, or vagina, that drained for more than 2 months. Magnetic resonance imaging or endosonography was performed to assess fistula tracts and the absence of abscesses. Patients were stratified into groups with simple or complex fistulas and randomly assigned to receive fibrin glue injections (n = 36) or only observation (n = 41) after removal of setons. The primary end point was clinical remission at week 8, defined as the absence of draining, perianal pain, or abscesses. At week 8, a fibrin glue injection was offered to patients who were not in remission. RESULTS Clinical remission was observed in 13 of the 34 patients (38%) of the fibrin glue group compared with 6 of the 37 (16%) in the observation group; these findings demonstrate the benefit of fibrin glue (odds ratio, 3. 2; 95% confidence interval: 1. 1-9. 8; P = . 04). The benefit seemed to be greater in patients with simple fistulas. Four patients in the fibrin glue group and 6 in the observation group had adverse events. CONCLUSIONS Fibrin glue injection is a simple, effective, and well-tolerated therapeutic option for patients with Crohn's disease and perianal fistula tracts.
A double-blind, placebo-controlled trial of oral human immunoglobulin for gastrointestinal dysfunction in children with autistic disorder
Handen BL, Melmed RD, Hansen RL, Aman MG, Burnham DL, Bruss JB, McDougle CJ
Journal of Autism and Developmental Disorders. 2009;39((5):):796-805.
Free full text
Controversy exists regarding the extent and possible causal relationship between gastrointestinal symptoms and autism. A randomized, double-blind, placebo-controlled, parallel groups, dose-ranging study of oral, human immunoglobulin (IGOH 140, 420, or 840 mg/day) was utilized with 125 children (ages 2-17 years) with autism and persistent GI symptoms. Endpoint analysis revealed no significant differences across treatment groups on a modified global improvement scale (validated in irritable bowel syndrome studies), number of daily bowel movements, days of constipation, or severity of problem behaviors. IGOH was well-tolerated; there were no serious adverse events. This study demonstrates the importance of conducting rigorous trials in children with autism and casts doubt on one GI mechanism presumed to exert etiological and/or symptomatic effects in this population.
Endoscopic injection with fibrin sealant versus epinephrine for arrest of peptic ulcer bleeding: a randomized, comparative trial
Lin HJ, Hsieh YH, Tseng GY, Perng CL, Chang FY, Lee SD
Journal of Clinical Gastroenterology. 2002;35((3):):218-21.
BACKGROUND endoscopic epinephrine and fibrin injection in the treatment of bleeding peptic ulcer are reported to be safe, effective, and easy to use. However, a wide range of rebleeding rates has been reported with epinephrine injection. GOALS to compare the hemostatic effects of endoscopic injection with fibrin sealant versus epinephrine. STUDY between December 1998 and July 2000, 51 patients with active bleeding or nonbleeding visible vessels entered this trial. The clinical parameters were comparable between both groups. In the epinephrine group, we injected 5 to 10 mL of 1:10,000 epinephrine, surrounding the bleeder. In the fibrin sealant group, we injected fibrin sealant 4 mL, surrounding the bleeder. RESULTS initial hemostasis was obtained in all enrolled patients. Rebleeding was more in the epinephrine group than in the fibrin sealant group (4 [15%] of 26 vs. 14 [56%] of 25, = 0.003 on the intention-to-treat basis, and 4 [16.7%] of 24 vs. 14 [58.3%] of 24, = 0.003 on the per protocol basis, respectively). Volume of blood transfusion, number of surgeries, hospital stay, and number of deaths were similar between both groups. CONCLUSION fibrin sealant injection is more effective in preventing rebleeding than epinephrine after endoscopic therapy, but this study showed no difference in outcomes with either therapy.
Epinephrine versus epinephrine plus fibrin glue injection in peptic ulcer bleeding: a prospective randomized trial
Pescatore P, Jornod P, Borovicka J, Pantoflickova D, Suter W, Meyenberger C, Blum AL, Dorta G
Gastrointestinal Endoscopy. 2002;55((3):):348-53.
BACKGROUND Peptic ulcer bleeding remains a disease with considerable morbidity and mortality. Epinephrine is the most widely used endoscopic injection agent, but bleeding recurs in 20% of high-risk cases. Fibrin glue might be an ideal injection agent, based on its physiologic properties, despite its demanding injection technique and high cost. The aim of this study was to determine whether the injection of fibrin glue in combination with epinephrine improves outcome for patients at high risk of recurrent bleeding. METHODS Patients were prospectively randomized to injection of epinephrine alone (n = 70) or epinephrine plus fibrin glue (n = 65). Endoscopy was repeated daily until the ulcer base was clean. All patients were treated with high-dose omeprazole. RESULTS Initial hemostasis was 100% in both groups. There was no significant overall difference in rates of recurrent bleeding (24.3% and 21.5%, respectively, for epinephrine and epinephrine plus fibrin). When patients were stratified according to Forrest criteria, no significant difference could be found, although there was a trend toward less recurrent bleeding after fibrin injection of actively bleeding ulcers. There was no significant difference in the proportions of patients who required surgery (10% and 6%, respectively, for epinephrine and epinephrine plus fibrin). Mortality was the same (3%) in each group. CONCLUSIONS Adding fibrin glue to epinephrine for injection treatment of bleeding peptic ulcers does not improve outcome. Fibrin glue might be of some value in selected cases.
Lack of clinical efficacy of additional factor XIII treatment in patients with steroid refractory colitis. The Factor XIII Study Group
Bregenzer N, Caesar I, Andus T, Hamling J, Malchow H, Schreiber S, Scholmerich J
Zeitschrift fur Gastroenterologie. 1999;37((10):):999-1004.
Patients with active ulcerative colitis have decreased levels of factor XIII (FXIII) activity, which is important for woundhealing. Recent uncontrolled studies claimed a beneficial effect of Factor XIII on clinical symptoms of ulcerative colitis, in particular intestinal bleeding. The objective of this trial was to evaluate the benefits of additional FXIII treatment in steroid-refractory patients with ulcerative colitis in a prospective, double blind, placebo-controlled study. A total of 28 patients were enrolled between October 1994 and January 1997. Primary objective of this study was the time until cessation of visible intestinal bleeding with 14 days after the start of treatment. Patients were treated for ten days either by i.v. application of FXIII concentrate or by placebo. The analysis of the primary efficacy criterion, cessation of intestinal bleeding, by a planned interim analysis showed no significant differences between the treatment groups (p = 0.8). This resulted in the termination of the study. The same applied to the CAI score. No patient in both treatment groups reached remission according to the colo-/-sigmoidoscopy score. Due to the high number of patients (16 of 28) who had to be excluded from the per-protocol analysis (e.g. changes to the concomitant medication) only the intention-to-treat population was analyzed. Overall the study showed no beneficial effect of additional FXIII treatment on active steroid-refractory ulcerative colitis. These results do not confirm previous open label studies which had reported a significant improvement of clinical symptoms.
Evaluation of using fibrin tissue adhesive (Beriplast) and preparations of thrombin and adrenalin in injection hemostasis methods for gastric and duodenal ulcer hemorrhage. Randomized, prospective clinical trial Polish
Babicki A, Dobosz M, Marczewski R, Wajda Z
Wiadomosci Lekarskie. 1997;50((Suppl 1, Pt 2):):383-7.
A prospective randomized trial involving 30 patients was performed to assess whether second-look endoscopy could improve the efficacy of injection therapy for bleeding peptic ulcers. The inclusion criteria were the presence of active arterial bleeding or a non-bleeding visible vessel at emergency endoscopy. All the patients received emergency injection of thrombin with adrenaline solution and were subsequently randomized (15 patients in each group). All the patients receive a second elective endoscopy within the first 24 hours with repeated injection of thrombin-adrenaline solution (Group I) or fibrin sealant-Beriplast-(Group II). A tendency towards better results was noted in the Group II. Recurrent bleeding was observed in 6.6% versus 26.6% patients in Group I. The need for emergency surgery occurred in (6.6% in Group I versus 0 in Group II) and length of hospital stay was (13.2 in Group I versus 7.4 in Group II [p < 0.05]). No mortality was observed in both of the groups. In conclusion, our data suggest the possibility of a small benefit with second-look endoscopy with repeated injection of fibrin sealant.
Randomised trial of single and repeated fibrin glue compared with injection of polidocanol in treatment of bleeding peptic ulcer
Rutgeerts P, Rauws E, Wara P, Swain P, Hoos A, Solleder E, Halttunen J, Dobrilla G, Richter G, Prassler R
BACKGROUND Although injection treatments for ulcer haemostasis seem to be effective, recurrent bleeding remains a serious problem. Large randomised clinical trials are required to show differences between treatment modalities for gastrointestinal bleeding. The aim of this study was to compare the safety and efficacy of repeated endoscopic injection of fibrin glue (FG) with that of single endoscopic injection of polidocanol in the prevention of recurrent bleeding. METHODS 854 patients with active gastroduodenal bleeding (spurting, oozing), or ulcers with a visible non-bleeding vessel, were randomly assigned one of three endoscopic treatments: single application of polidocanol 1%, single application of FG, or daily repeated application of FG until the visible vessel had disappeared. All patients were pretreated with local injection of epinephrine (1/10,000), and had daily repeat endoscopies until the vessel observed at initial endoscopy was no longer visible. FINDINGS Recurrent bleeding rates among the 790 patients in whom the rates could be assessed were 58 (22.8%) of 254 in the polidocranol group, 51 (19.2%) of 266 in the FG-single group, and 41 (15.2%) of 270 in the FG-repeated group. The difference between FG-repeated treatment and polidocanol was significant (p = 0.036). Treatment failed, making other treatments (including surgery) necessary, in 34 (13.0%) of 261 in the polidocanol group, 34 (12.4%) of 274 in the FG-single group, and 21 (7.7%) of 274 in the FG-repeated group. The difference between FG-repeated treatment and polidocanol was significant (p = 0.046). The 30-day-mortality rates were low in all three treatment groups (polidocanol 4.7%; FG-single treatment 5.3%, FG-repeated treatment 4.3%). The safety profiles of the three treatment strategies were similar. INTERPRETATION Repeated injection with FG glue is significantly more effective than injection with polidocanol 1% in the treatment of bleeding from gastroduodenal ulcers.