Abstract

PURPOSE Peptic ulcer is a multifactorial and complex disease and affects a wide range of people worldwide. We provided a novel therapeutic approach for peptic ulcer and observed its effect. METHODS Peptic ulcer patients were enrolled from 2016 to 2017 in Chongqing and randomly assigned to two groups: a control group that used only rabeprazole and a platelet-rich plasma (PRP) group that received a combination therapy of autologous PRP (aPRP) and rabeprazole. The therapeutic effect was assessed via the ulcer size and symptom score. RESULTS A total of 27 patients were included (12 patients in the control group and 15 patients in the PRP group) in this study. Our results showed that all participants have healed in 30 days, and there was no significant difference in healing time between the PRP group and the control group in different independent variables. However, regression analysis revealed that the healing time was 6.99 days shorter in the PRP group than that in the control group, and patients with higher symptom scores in the initial examination need more time to heal during treatment. Endoscopic results showed that the repaired ulcer in the PRP group was more similar to the normal gastric mucosa tissue than that the control group. CONCLUSION This study showed an encouraging preliminary result that aPRP has a positive result in patients with peptic ulcer and seems to be a better choice for refractory peptic ulcer treatment. Although further follow-up studies are needed to determine the duration of efficacy of aPRP, the approach will be helpful in improving the clinical treatment of peptic ulcer.

Abstract

BACKGROUND Acute upper gastrointestinal bleeding is a leading indication for red blood cell (RBC) transfusion worldwide, although optimal thresholds for transfusion are debated. METHODS We searched MEDLINE, Embase, CENTRAL, CINAHL, and the Transfusion Evidence Library from inception to Oct 20, 2016, for randomised controlled trials comparing restrictive and liberal RBC transfusion strategies for acute upper gastrointestinal bleeding. Main outcomes were mortality, rebleeding, ischaemic events, and mean RBC transfusion. We computed pooled estimates for each outcome by random effects meta-analysis, and individual participant data for a cluster randomised trial were re-analysed to facilitate meta-analysis. We compared treatment effects between patient subgroups, including patients with liver cirrhosis, patients with non-variceal upper gastrointestinal bleeding, and patients with ischaemic heart disease at baseline. FINDINGS We included four published and one unpublished randomised controlled trial, totalling 1965 participants. The number of RBC units transfused was lower in the restrictive transfusion group than in the liberal transfusion group (mean difference -1.73 units, 95% CI -2.36 to -1.11, p<0.0001). Restrictive transfusion was associated with lower risk of all-cause mortality (relative risk [RR] 0.65, 95% CI 0.44-0.97, p=0.03) and rebleeding overall (0.58, 0.40-0.84, p=0.004). We detected no difference in risk of ischaemic events. There were no statistically significant differences in the subgroups. INTERPRETATION These results support more widespread implementation of restrictive transfusion policies for adults with acute upper gastrointestinal bleeding. FUNDING None.

Abstract

BACKGROUND Acute upper gastrointestinal bleeding is a common and potentially life-threatening emergency with substantial mortality. Fresh frozen plasma (FFP), a good source of coagulation factors, might be an ideal injection agent based on its physiologic properties. Therefore, we evaluated the role of FFP as a hemostatic agent in patients with high-risk bleeding peptic ulcers. MATERIALS AND METHODS From August 2015 to April 2016, 108 consecutive patients with high-risk bleeding ulcers were admitted to our university hospital. They were randomly assigned to undergo injection of epinephrine alone (A) or epinephrine plus FFP (B). The primary outcomes assessed were the initial hemostasis, recurrent bleeding, hospital stay, blood transfusion, surgery rate, and 14-day mortality. RESULTS Initial hemostasis was achieved in 47 of 50 patients (94%) in the Group A and 49 of 50 patients (98%) in the Group B (P = 0.61). There were no significant differences in the rate of recurrent bleeding between Group A (14%) and Group B (8%) (P = 0.52). We found no significant differences between Group A and Group B with respect to the surgery rate, bleeding death, procedure-related death, and duration of hospitalization (P > 0.05). CONCLUSION It is concluded the injection of epinephrine alone was equally effective as injection of epinephrine plus FFP to endoscopic hemostasis. Epinephrine alone and epinephrine plus FFP were not different in recurrent bleeding, rate of surgery, blood transfusion, or mortality.

Abstract

BACKGROUND Transfusion thresholds for acute upper gastrointestinal bleeding are controversial. So far, only three small, underpowered studies and one single-centre trial have been done. Findings from the single-centre trial showed reduced mortality with restrictive red blood cell (RBC) transfusion. We aimed to assess whether a multicentre, cluster randomised trial is a feasible method to substantiate or refute this finding. METHODS In this pragmatic, open-label, cluster randomised feasibility trial, done in six university hospitals in the UK, we enrolled all patients aged 18 years or older with new presentations of acute upper gastrointestinal bleeding, irrespective of comorbidity, except for exsanguinating haemorrhage. We randomly assigned hospitals (1:1) with a computer-generated randomisation sequence (random permuted block size of 6, without stratification or matching) to either a restrictive (transfusion when haemoglobin concentration fell below 80 g/L) or liberal (transfusion when haemoglobin concentration fell below 100 g/L) RBC transfusion policy. Neither patients nor investigators were masked to treatment allocation. Feasibility outcomes were recruitment rate, protocol adherence, haemoglobin concentration, RBC exposure, selection bias, and information to guide design and economic evaluation of the phase 3 trial. Main exploratory clinical outcomes were further bleeding and mortality at day 28. We did analyses on all enrolled patients for whom an outcome was available. This trial is registered, ISRCTN85757829 and NCT02105532. FINDINGS Between Sept 3, 2012, and March 1, 2013, we enrolled 936 patients across six hospitals (403 patients in three hospitals with a restrictive policy and 533 patients in three hospitals with a liberal policy). Recruitment rate was significantly higher for the liberal than for the restrictive policy (62% vs 55%; p=004). Despite some baseline imbalances, Rockall and Blatchford risk scores were identical between policies. Protocol adherence was 96% (SD 10) in the restrictive policy vs 83% (25) in the liberal policy (difference 14%; 95% CI 7-21; p=0005). Mean last recorded haemoglobin concentration was 116 (SD 24) g/L for patients on the restrictive policy and 118 (20) g/L for those on the liberal policy (difference -20 [95% CI -120 to 70]; p=050). Fewer patients received RBCs on the restrictive policy than on the liberal policy (restrictive policy 133 [33%] vs liberal policy 247 [46%]; difference -12% [95% CI -35 to 11]; p=023), with fewer RBC units transfused (mean 12 [SD 21] vs 19 [28]; difference -07 [-16 to 03]; p=012), although these differences were not significant. We noted no significant difference in clinical outcomes. INTERPRETATION A cluster randomised design led to rapid recruitment, high protocol adherence, separation in degree of anaemia between groups, and non-significant reduction in RBC transfusion in the restrictive policy. A large cluster randomised trial to assess the effectiveness of transfusion strategies for acute upper gastrointestinal bleeding is both feasible and essential before clinical practice guidelines change to recommend restrictive transfusion for all patients with acute upper gastrointestinal bleeding. FUNDING NHS Blood and Transplant Research and Development.Copyright © 2015 Elsevier Ltd. All rights reserved.

Abstract

Acute upper gastrointestinal bleeding (AUGIB) is the commonest reason for hospitalization with hemorrhage in the UK and the leading indication for transfusion of red blood cells (RBCs). Observational studies suggest an association between more liberal RBC transfusion and adverse patient outcomes, and a recent randomised trial reported increased further bleeding and mortality with a liberal transfusion policy. TRIGGER (Transfusion in Gastrointestinal Bleeding) is a pragmatic, cluster randomized trial which aims to evaluate the feasibility and safety of implementing a restrictive versus liberal RBC transfusion policy in adult patients admitted with AUGIB. The trial will take place in 6 UK hospitals, and each centre will be randomly allocated to a transfusion policy. Clinicians throughout each hospital will manage all eligible patients according to the transfusion policy for the 6-month trial recruitment period. In the restrictive centers, patients become eligible for RBC transfusion when their hemoglobin is <8 g/dL. In the liberal centers patients become eligible for transfusion once their hemoglobin is <10 g/dL. All clinicians will have the discretion to transfuse outside of the policy but will be asked to document the reasons for doing so. Feasibility outcome measures include protocol adherence, recruitment rate, and evidence of selection bias. Clinical outcome measures include further bleeding, mortality, thromboembolic events, and infections. Quality of life will be measured using the EuroQol EQ-5D at day 28, and the costs associated with hospitalization for AUGIB in the UK will be estimated. Consent will be sought from participants or their representatives according to patient capacity for use of routine hospital data and day 28 follow up. The study has ethical approval for conduct in England and Scotland. Results will be analysed according to a pre-defined statistical analysis plan and disseminated in peer reviewed publications to relevant stakeholders. The results of this study will inform the feasibility and design of a phase III randomized trial. Copyright 2013 Elsevier Inc. All rights reserved.

Abstract

BACKGROUND Previous research has suggested an association between more liberal red blood cell (RBC) transfusion and greater risk of further bleeding and mortality following acute upper gastrointestinal bleeding (AUGIB). METHODS AND DESIGN The Transfusion in Gastrointestinal Bleeding (TRIGGER) trial is a pragmatic cluster-randomised feasibility trial which aims to evaluate the feasibility of implementing a restrictive vs. liberal RBC transfusion policy for adult patients admitted to hospital with AUGIB in the UK. This trial will help to inform the design and methodology of a phase III trial. The protocol for TRIGGER has been published in Transfusion Medicine Reviews. Recruitment began in September 2012 and was completed in March 2013. This update presents the statistical analysis plan, detailing how analysis of the TRIGGER trial will be performed. It is hoped that prospective publication of the full statistical analysis plan will increase transparency and give readers a clear overview of how TRIGGER will be analysed. TRIAL REGISTRATION ISRCTN85757829.

Abstract

BACKGROUND The hemoglobin threshold for transfusion of red cells in patients with acute gastrointestinal bleeding is controversial. We compared the efficacy and safety of a restrictive transfusion strategy with those of a liberal transfusion strategy. METHODS We enrolled 921 patients with severe acute upper gastrointestinal bleeding and randomly assigned 461 of them to a restrictive strategy (transfusion when the hemoglobin level fell below 7 g per deciliter) and 460 to a liberal strategy (transfusion when the hemoglobin fell below 9 g per deciliter). Randomization was stratified according to the presence or absence of liver cirrhosis. RESULTS A total of 225 patients assigned to the restrictive strategy (51%), as compared with 65 assigned to the liberal strategy (15%), did not receive transfusions (P<0.001). The probability of survival at 6 weeks was higher in the restrictive-strategy group than in the liberal-strategy group (95% vs. 91%; hazard ratio for death with restrictive strategy, 0.55; 95% confidence interval [CI], 0.33 to 0.92; P=0.02). Further bleeding occurred in 10% of the patients in the restrictive-strategy group as compared with 16% of the patients in the liberal-strategy group (P=0.01), and adverse events occurred in 40% as compared with 48% (P=0.02). The probability of survival was slightly higher with the restrictive strategy than with the liberal strategy in the subgroup of patients who had bleeding associated with a peptic ulcer (hazard ratio, 0.70; 95% CI, 0.26 to 1.25) and was significantly higher in the subgroup of patients with cirrhosis and Child-Pugh class A or B disease (hazard ratio, 0.30; 95% CI, 0.11 to 0.85), but not in those with cirrhosis and Child-Pugh class C disease (hazard ratio, 1.04; 95% CI, 0.45 to 2.37). Within the first 5 days, the portal-pressure gradient increased significantly in patients assigned to the liberal strategy (P=0.03) but not in those assigned to the restrictive strategy. CONCLUSIONS As compared with a liberal transfusion strategy, a restrictive strategy significantly improved outcomes in patients with acute upper gastrointestinal bleeding. (Funded by Fundacio Investigacio Sant Pau; ClinicalTrials.gov number, NCT00414713.).

Abstract

AIM: To compare the outcome of upper gastrointestinal bleeding (UGIB) between patients receiving restrictive and liberal transfusion. METHODS PubMed, EMBASE, and Cochrane Library databases were employed to identify all relevant randomized controlled trials regarding the outcome of UGIB after restrictive or liberal transfusion. Primary outcomes were death and rebleeding. Secondary outcomes were length of hospitalization, amount of blood transfused, and hematocrit and hemoglobin at discharge or after expansion. RESULTS Overall, 4 papers were included in this meta-analysis. The incidence of death was significantly lower in patients receiving restrictive transfusion than those receiving liberal transfusion (OR: 0.52, 95%CI: 0.31-0.87, P = 0.01). The incidence of rebleeding was lower in patients receiving restrictive transfusion than those receiving liberal transfusion, but this difference did not reach any statistical significance (OR: 0.26, 95%CI: 0.03-2.10, P = 0.21). Compared with those receiving liberal transfusion, patients receiving restrictive transfusion had a significantly shorter length of hospitalization (standard mean difference: -0.17, 95%CI: -0.30--0.04, P = 0.009) and a significantly smaller amount of blood transfused (standard mean difference: -0.74, 95%CI: -1.15--0.32, P = 0.0005) with a lower hematocrit and hemoglobin level at discharge or after expansion. CONCLUSION Restrictive transfusion should be employed in patients with UGIB.

Abstract

BACKGROUND : There exists uncertainty as to the optimal platelet values when managing patients with nonvariceal upper gastrointestinal (GI) bleeding. GOALS AND STUDY A systematic review was carried out to determine the optimal approach when managing patients with thrombocytopenia in the setting of nonvariceal upper GI bleeding. RESULTS : Eighteen of 803 potential articles were selected and reviewed, including 4 randomized controlled trials and 6 cohort studies. The only empirical clinical data available pertained to the management of hematology or oncology patients. There was no high-level evidence that determined the proper threshold of platelet transfusion specifically in GI bleeding. We were, therefore, limited to include principally consensus opinions, recommendations, and guidelines for platelet transfusion trigger as they apply to the treatment (including prophylaxis) of bleeding in general, with a paucity of data addressing major bleeding, let alone bleeding from a gastroenterologic origin. Randomized clinical trials were individually underpowered in allowing definitive conclusions, even though resulting recommendations were supported by similarly underpowered retrospective and prospective observational studies. CONCLUSIONS : There exist a paucity of data to recommend optimal therapeutic platelet count targets in patients with active GI bleeding. Based principally on expert opinion recommendations, we propose a count of 50x10/L. Some professional associations have suggested in very specific clinical settings (postcardiopulmonary bypass surgery or central nervous system trauma) a higher value of up to 100x10/L. Properly designed randomized trials are required to more precisely address this important clinical question.

Abstract

With the establishment of the inadequate efficiency of atropines and oximes in reducing morbidity and mortality of patients poisoned by organophosphates, more attention is given to using other methods such as Fresh Frozen Plasma (FFP) as a bioscavenger to mop up organophosphate toxins. This randomized clinical trial was conducted on 56 organophosphate poisoned patients who were randomly assigned to the FFP and control groups in order of admission. The routine treatment in both groups included atropine and, in moderate to severe cases of poisoning, pralidoxime. The FFP group received four packs of FFP as stat dose at the beginning of treatment. No significant difference was seen between the two groups on the atropine and pralidoxime dosage, hospitalization length and mortality. The present study showed that using four packs of FFP as stat dose at the onset of treatment had no significant effect on the clinical course of organophosphate poisoned patients.