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Efficacy and adverse effects of insulin versus plasmapheresis in patients with hypertriglyceridemia-3-induced acute pancreatitis: a systematic review and meta-analysis
Piplani, S., Jain, A., Singh, K., Gulati, S., Chaturvedi, S., Bejugam, V. R., Brown, D., Asuzu, C., Kolli, S. T., Shah, U., et al
Annals of gastroenterology. 2024;37(1):109-116
Abstract
BACKGROUND Hypertriglyceridemia is a common cause of acute pancreatitis (AP). This literature review compared the effectiveness and adverse events of insulin therapy, with or without heparin, and plasmapheresis, in reducing triglyceride levels in patients with hypertriglyceridemia-induced AP. METHODS Systematic reviews, meta-analyses, evidence syntheses, editorials, commentaries, protocols, abstracts, theses and preprints were excluded. Review Manager was used to conduct the meta-analysis. The literature search yielded 2765 articles, but only 5 were included in the systematic review and meta-analysis and the total number of participants in the review was 269. RESULTS From this study's analysis, insulin ± heparin was more successful in reducing triglyceride levels than plasmapheresis (standardized mean difference -0.37, 95% confidence interval [CI] 0.99 to 0.25; P=0.25). Insulin ± heparin therapy had a lower mortality rate than plasmapheresis (risk ratio [RR] 0.70, 95%CI 0.25-1.95). Hypotension, hypoglycemia, and acute renal failure were less common in the plasmapheresis therapy group than in insulin ± heparin therapy (RR 1.13, 95%CI 0.46-2.81, RR 3.90, 95%CI 0.45-33.78, and RR 0.48, 95%CI 0.02-13.98 for hypotension, hypoglycemia, and acute renal failure, respectively). CONCLUSIONS This study found no significant difference in mortality between insulin ± heparin therapy and plasmapheresis used for the reduction in triglyceride levels. It is notable that no substantial differences were observed in the most common side-effects encountered during these therapies, thus indicating non-inferiority.
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Tranexamic acid for gastrointestinal bleeding: can a reduction in the risk of death be discounted? A systematic review and meta-analysis of individual patient data from 64 724 bleeding patients
Ker, K., Mansukhani, R., Shakur-Still, H., Arribas, M., Beaumont, D., Roberts, I.
BMJ open. 2023;13(2):e059982
Abstract
OBJECTIVES HALT-IT was an international, randomised trial which assessed the effects of tranexamic acid (TXA) in 12 009 patients with gastrointestinal (GI) bleeding. The results found no evidence that TXA reduces death. It is widely accepted that results of trials should be interpreted in the context of other relevant evidence. We conducted a systematic review and individual patient data (IPD) meta-analysis to assess if the results of HALT-IT are compatible with evidence for TXA in other bleeding conditions. DESIGN Systematic review and IPD meta-analysis of randomised trials involving ≥5000 patients assessing TXA for bleeding. We searched our Antifibrinolytics Trials Register on 1 November 2022. Two authors extracted data and assessed risk of bias. DATA SYNTHESIS We used a one-stage model to analyse IPD in a regression model stratified by trial. We assessed heterogeneity of the effect of TXA on death within 24 hours and vascular occlusive events (VOEs). RESULTS We included IPD for 64 724 patients from four trials involving patients with traumatic, obstetric and GI bleeding. Risk of bias was low. There was no evidence for heterogeneity between trials for the effect of TXA on death or for the effect of TXA on VOEs. TXA reduced the odds of death by 16% (OR=0.84, 95% CI: 0.78 to 0.91, p<0.0001; p-heterogeneity=0.40). In patients treated within 3 hours of bleeding onset, TXA reduced the odds of death by 20% (0.80, 0.73 to 0.88, p<0.0001; p-heterogeneity=0.16). TXA did not increase the odds of VOEs (0.94, 0.81 to 1.08, p for effect=0.36; p-heterogeneity=0.27). CONCLUSIONS There is no evidence for statistical heterogeneity between trials assessing the effect of TXA on death or VOEs in different bleeding conditions. When the HALT-IT results are considered in the context of other evidence, a reduction in the risk of death cannot be discounted. TRIAL REGISTRATION NUMBER PROSPERO CRD42019128260.Cite Now.
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Erythromycin prior to endoscopy for acute upper gastrointestinal haemorrhage
Adão, D., Gois, A. F., Pacheco, R. L., Pimentel, C. F., Riera, R.
The Cochrane Database of Systematic Reviews. 2023;2(2):Cd013176
Abstract
BACKGROUND Upper endoscopy is the definitive treatment for upper gastrointestinal haemorrhage (UGIH). However, up to 13% of people who undergo upper endoscopy will have incomplete visualisation of the gastric mucosa at presentation. Erythromycin acts as a motilin receptor agonist in the upper gastrointestinal (GI) tract and increases gastric emptying, which may lead to better quality of visualisation and improved treatment effectiveness. However, there is uncertainty about the benefits and harms of erythromycin in UGIH. OBJECTIVES To evaluate the benefits and harms of erythromycin before endoscopy in adults with acute upper gastrointestinal haemorrhage, compared with any other treatment or no treatment/placebo. SEARCH METHODS We used standard, extensive Cochrane search methods. The latest search date was 15 October 2021. SELECTION CRITERIA We included randomised controlled trials (RCTs) that investigated erythromycin before endoscopy compared to any other treatment or no treatment/placebo before endoscopy in adults with acute UGIH. DATA COLLECTION AND ANALYSIS We used standard Cochrane methods. Our primary outcomes were 1. UGIH-related mortality and 2. serious adverse events. Our secondary outcomes were 1. all-cause mortality, 2. visualisation of gastric mucosa, 3. non-serious adverse events, 4. rebleeding, 5. blood transfusion, and 5. rescue invasive intervention. We used GRADE criteria to assess the certainty of the evidence for each outcome. MAIN RESULTS We included 11 RCTs with 878 participants. The mean age ranged from 53.13 years to 64.5 years, and most participants were men (72.3%). One RCT included only non-variceal haemorrhage, one included only variceal haemorrhage, and eight included both aetiologies. We defined short-term outcomes as those occurring within one week of initial endoscopy. Erythromycin versus placebo Three RCTs (255 participants) compared erythromycin with placebo. There were no UGIH-related deaths. The evidence is very uncertain about the short-term effects of erythromycin compared with placebo on serious adverse events (risk difference (RD) -0.01, 95% confidence interval (CI) -0.04 to 0.02; 3 studies, 255 participants; very low certainty), all-cause mortality (RD 0.00, 95% CI -0.03 to 0.03; 3 studies, 255 participants; very low certainty), non-serious adverse events (RD 0.01, 95% CI -0.03 to 0.05; 3 studies, 255 participants; very low certainty), and rebleeding (risk ratio (RR) 0.63, 95% CI 0.13 to 2.90; 2 studies, 195 participants; very low certainty). Erythromycin may improve gastric mucosa visualisation (mean difference (MD) 3.63 points on 16-point ordinal scale, 95% CI 2.20 to 5.05; higher MD means better visualisation; 2 studies, 195 participants; low certainty). Erythromycin may also result in a slight reduction in blood transfusion (MD -0.44 standard units of blood, 95% CI -0.86 to -0.01; 3 studies, 255 participants; low certainty). Erythromycin plus nasogastric tube lavage versus no intervention/placebo plus nasogastric tube lavage Six RCTs (408 participants) compared erythromycin plus nasogastric tube lavage with no intervention/placebo plus nasogastric tube lavage. There were no UGIH-related deaths and no serious adverse events. The evidence is very uncertain about the short-term effects of erythromycin plus nasogastric tube lavage compared with no intervention/placebo plus nasogastric tube lavage on all-cause mortality (RD -0.02, 95% CI -0.08 to 0.03; 3 studies, 238 participants; very low certainty), visualisation of the gastric mucosa (standardised mean difference (SMD) 0.48 points on 10-point ordinal scale, 95% CI 0.10 to 0.85; higher SMD means better visualisation; 3 studies, 170 participants; very low certainty), non-serious adverse events (RD 0.00, 95% CI -0.05 to 0.05; 6 studies, 408 participants; very low certainty), rebleeding (RR 1.13, 95% CI 0.63 to 2.02; 1 study, 169 participants; very low certainty), and blood transfusion (MD -1.85 standard units of blood, 95% CI -4.34 to 0.64; 3 studies, 180 participants; very low certainty). Erythromycin versus nasogastric tube lavage Four RCTs (287 participants) compared erythromycin with nasogastric tube lavage. There were no UGIH-related deaths and no serious adverse events. The evidence is very uncertain about the short-term effects of erythromycin compared with nasogastric tube lavage on all-cause mortality (RD 0.02, 95% CI -0.05 to 0.08; 3 studies, 213 participants; very low certainty), visualisation of the gastric mucosa (RR 1.19, 95% CI 0.79 to 1.79; 2 studies, 198 participants; very low certainty), non-serious adverse events (RD -0.10, 95% CI -0.34 to 0.13; 3 studies, 213 participants; very low certainty), rebleeding (RR 0.77, 95% CI 0.40 to 1.49; 1 study, 169 participants; very low certainty), and blood transfusion (median 2 standard units of blood, interquartile range 0 to 4 in both groups; 1 study, 169 participants; very low certainty). Erythromycin plus nasogastric tube lavage versus metoclopramide plus nasogastric tube lavage One RCT (30 participants) compared erythromycin plus nasogastric tube lavage with metoclopramide plus nasogastric tube lavage. The evidence is very uncertain about the effects of erythromycin plus nasogastric tube lavage on all the reported outcomes (serious adverse events, visualisation of gastric mucosa, non-serious adverse events, and blood transfusion). AUTHORS' CONCLUSIONS We are unsure if erythromycin before endoscopy in people with UGIH has any clinical benefits or harms. However, erythromycin compared with placebo may improve gastric mucosa visualisation and result in a slight reduction in blood transfusion.
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Treatment Options for Gastrointestinal Bleeding Blue Rubber Bleb Nevus Syndrome: a systematic review
Rimondi A, Sorge A, Murino A, Nandi N, Scaramella L, Vecchi M, Tontini GE, Elli L
Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society. 2023
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Abstract
INTRODUCTION Blue Rubber Bleb Nevus Syndrome (BRBNS) is a rare challenging cause of gastrointestinal bleeding. We performed a systematic review of case reports and case series on BRBNS to gather information on the treatment options currently available. METHOD All studies reporting a case of BRBNS in humans were evaluated. Papers were ruled out whether CARE criteria and explanations on patient's selection, ascertainment, causality, and reporting were not respected or identified. PROSPERO 2021 CRD 42021286982. RESULTS BRNBS was treated in 106 cases from 76 reports. 57.5% of the population was under 18 years old, and up to 50% of the cases reported a previous treatment. Clinical success was achieved in 98 patients (92.4%). Three main types of interventions were identified: systemic drug therapy, endoscopy and surgery. After BRBNS recurrence or previous therapy failure, systemic drug therapy emerged as a preferred second-line treatment over endoscopy (p=0.01), but with a higher rate of reported adverse events when compared with surgery and endoscopy (p < 0.001). Endoscopic treatment was associated with a higher number of required sessions to achieve complete eradication when compared with surgery (p < 0.001). No differences between the three main areas were found in the overall follow-up time (p=0.19) and in the recurrence rate (p=0.45). CONCLUSION Endoscopy, surgery and systemic drug therapy are feasible treatment options for BRBNS. Systemic drug therapy was the favourite second-line treatment after endoscopic failure or recurrence of BRBNS, but adverse events were more frequently reported.
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Effects of high-dose versus low-dose proton pump inhibitors for treatment of gastrointestinal ulcer bleeding: a meta-analysis of randomized controlled trials
Zhu, W., Chen, L., Zhang, J., Wang, P.
The Journal of International Medical Research. 2022;50(4):3000605211067396
Abstract
BACKGROUND We performed a meta-analysis to compare the effects of high-dose (80 mg/day) versus low-dose (40 mg/day) proton pump inhibitors (PPIs) on gastrointestinal ulcer bleeding. METHODS We retrieved studies of randomized controlled trials of PPIs administered according to different schedules for the treatment of gastrointestinal ulcer bleeding from Medline, Embase, Web of Science, Clinical Trials, and the Cochrane Database in April 2020. RESULTS Nine randomized controlled trials including 2329 patients were included in this meta-analysis. There were no significant differences in the incidences of re-bleeding, operation intervention, postoperative mortality, and length of hospital stay between the low-dose and high-dose groups. However, the blood transfusion volume was significantly higher in the high-dose group. CONCLUSION Compared with low-does PPIs, high-dose PPIs had no effect on the incidence of re-bleeding, operation intervention, or postoperative mortality, and did not reduce hospital stay in patients treated with endoscopic hemostasis for gastrointestinal bleeding.
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Effectiveness of hemostatic powders in lower gastrointestinal bleeding: a systematic review and meta-analysis
Facciorusso A, Bertini M, Bertoni M, Tartaglia N, Pacilli M, Ramai D, Mohan BP, Chandan S, Ambrosi A, Sacco R
Endoscopy international open. 2021;9(8):E1283-e1290
Abstract
Background and study aims There is limited evidence on the effectiveness of hemostatic powders in the management of lower gastrointestinal bleeding (LGIB). We aimed to provide a pooled estimate of their effectiveness and safety based on the current literature. Patients and methods Literature review was based on computerized bibliographic search of the main databases through to December 2020. Immediate hemostasis, rebleeding rate, adverse events, and mortality were the outcomes of the analysis. Pooled effects were calculated using a random-effects model. Results A total of 9 studies with 194 patients were included in the meta-analysis. Immediate hemostasis was achieved in 95 % of patients (95 % confidence interval [CI] 91.6 %-98.5 %), with no difference based on treatment strategy or bleeding etiology. Pooled 7- and 30-day rebleeding rates were 10.9 % (95 %CI 4.2 %-17.6 %) and 14.3 % (95 %CI 7.3 %-21.2 %), respectively. Need for embolization and surgery were 1.7 % (95 %CI 0 %-3.5 %) and 2.4 % (95 %CI 0.3 %-4.6 %), respectively. Overall, two patients (1.9 %, 95 %CI 0 %-3.8 %) experienced mild abdominal pain after powder application, and three bleeding-related deaths (2.3 %, 95 %CI 0.2 %-4.3 %) were registered in the included studies. Conclusion Novel hemostatic powders represent a user-friendly and effective tool in the management of lower gastrointestinal bleeding.
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Computer-Aided Diagnosis of Gastrointestinal Ulcer and Hemorrhage Using Wireless Capsule Endoscopy: Systematic Review and Diagnostic Test Accuracy Meta-analysis
Bang CS, Lee JJ, Baik GH
Journal of medical Internet research. 2021;23(12):e33267
Abstract
BACKGROUND Interpretation of capsule endoscopy images or movies is operator-dependent and time-consuming. As a result, computer-aided diagnosis (CAD) has been applied to enhance the efficacy and accuracy of the review process. Two previous meta-analyses reported the diagnostic performance of CAD models for gastrointestinal ulcers or hemorrhage in capsule endoscopy. However, insufficient systematic reviews have been conducted, which cannot determine the real diagnostic validity of CAD models. OBJECTIVE To evaluate the diagnostic test accuracy of CAD models for gastrointestinal ulcers or hemorrhage using wireless capsule endoscopic images. METHODS We conducted core databases searching for studies based on CAD models for the diagnosis of ulcers or hemorrhage using capsule endoscopy and presenting data on diagnostic performance. Systematic review and diagnostic test accuracy meta-analysis were performed. RESULTS Overall, 39 studies were included. The pooled area under the curve, sensitivity, specificity, and diagnostic odds ratio of CAD models for the diagnosis of ulcers (or erosions) were .97 (95% confidence interval, .95-.98), .93 (.89-.95), .92 (.89-.94), and 138 (79-243), respectively. The pooled area under the curve, sensitivity, specificity, and diagnostic odds ratio of CAD models for the diagnosis of hemorrhage (or angioectasia) were .99 (.98-.99), .96 (.94-0.97), .97 (.95-.99), and 888 (343-2303), respectively. Subgroup analyses showed robust results. Meta-regression showed that published year, number of training images, and target disease (ulcers vs erosions, hemorrhage vs angioectasia) was found to be the source of heterogeneity. No publication bias was detected. CONCLUSIONS CAD models showed high performance for the optical diagnosis of gastrointestinal ulcer and hemorrhage in wireless capsule endoscopy.
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Oral Proton Pump Inhibitors May Be as Effective as Intravenous in Peptic Ulcer Bleeding: A Systematic Review and Meta-analysis
Csiki E, Szabó H, Hanák L, Szakács Z, Kiss S, Vörhendi N, Pécsi D, Hegyi E, Hegyi P, Erőss B
Clinical and translational gastroenterology. 2021;12(4):e00341
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Abstract
INTRODUCTION Current guidelines recommend intravenous (IV) proton pump inhibitor (PPI) therapy in peptic ulcer bleeding (PUB). We aimed to compare the efficacy of oral and IV administration of PPIs in PUB. METHODS We performed a systematic search in 4 databases for randomized controlled trials, which compared the outcomes of oral PPI therapy with IV PPI therapy for PUB. The primary outcomes were 30-day recurrent bleeding and 30-day mortality. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for dichotomous outcomes, while weighted mean differences (WMDs) with CI were calculated for continuous outcomes in meta-analysis. The protocol was registered a priori onto PROSPERO (CRD42020155852). RESULTS A total of 14 randomized controlled trials reported 1,951 peptic ulcer patients, 977 and 974 of which were in the control and intervention groups, respectively. There were no statistically significant differences between oral and IV administration regarding 30-day rebleeding rate (OR = 0.96, CI: 0.65-1.44); 30-day mortality (OR = 0.70, CI: 0.35-1.40); length of hospital stay (WMD = -0.25, CI: -0.93 to -0.42); transfusion requirements (WMD = -0.09, CI: -0.07 to 0.24); need for surgery (OR = 0.91, CI: 0.40-2.07); further endoscopic therapy (OR = 1.04, CI: 0.56-1.93); and need for re-endoscopy (OR = 0.81, CI: 0.52-1.28). Heterogeneity was negligible in all analysis, except for the analysis on the length of hospitalization (I2 = 82.3%, P = 0.001). DISCUSSION Recent evidence suggests that the oral administration of PPI is not inferior to the IV PPI treatment in PUB after endoscopic management, but further studies are warranted.
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Is There a Role for Tranexamic Acid in Upper GI Bleeding? A Systematic Review and Meta-Analysis
Burke E, Harkins P, Ahmed I
Surgery research and practice. 2021;2021:8876991
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Editor's Choice
Abstract
INTRODUCTION Upper gastrointestinal (GI) bleeding is associated with increased morbidity and mortality. Tranexamic acid (TXA) is an antifibrinolytic agent which is licensed in the management of haemorrhage associated with trauma. It has been suggested that tranexamic acid may be able to play a role in upper GI bleeding. However, there is currently no recommendation to support this. AIM: The aim of this study was to synthesise available evidence of the effect of TXA on upper GI bleeding. METHODS AND MATERIALS A systematic review was conducted. PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for relevant studies. A random effects meta-analysis was performed to determine the risk ratio of primary and secondary outcomes pertaining to the use of TXA in upper GI bleeding. RESULTS A total of 8 studies were included in this systematic review. The total number of patients in all studies was 12994 including 4550 females (35%) and 8444 males (65%). The mean age of participants in 6 of the studies was 59.3; however the mean age for either intervention or placebo group was not reported in two of the studies. All studies reported on the effect of TXA on mortality, and the risk ratio was 0.95; however, with the 95% CI ranging from 0.80 to 1.13, this was not statistically significant. 6 of the studies reported on rebleeding rate, the risk ratio was 0.64, and with a 95% CI ranging from 0.47 to 0.86, this was statistically significant. 3 of the studies reported on the risk of adverse thromboembolic events, and the risk ratio was 0.93; however, the 95% CI extended from 0.62 to 1.39 and so was not statistically significant. 7 of the studies reported on the need for surgery, and the risk ratio was 0.59 and was statistically significant with a 95% CI ranging from 0.38 to 0.94. CONCLUSION In conclusion, the use of TXA in upper GI bleeding appears to have a beneficial effect in terms of decreasing the risk of re-bleeding and decreasing the need for surgery. However, we could not find a statistically significant effect on need for blood transfusions, risk of thromboembolic events, or effect on mortality. Future randomised controlled trials may elucidate these outcomes.
PICO Summary
Population
Patients with upper gastrointestinal (GI) bleeding (8 studies, n= 12,994).
Intervention
Meta-analysis to synthesise available evidence of the effect of tranexamic acid (TXA) on upper GI bleeding.
Comparison
Outcome
All studies reported on the effect of TXA on mortality, and the risk ratio was 0.95; however, this was not statistically significant. 6 of the studies reported on rebleeding rate, the risk ratio was 0.64, and this was statistically significant. 3 of the studies reported on the risk of adverse thromboembolic events, and the risk ratio was 0.93; however, was not statistically significant. 7 of the studies reported on the need for surgery, and the risk ratio was 0.59 and was statistically significant.
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Prophylactic transcatheter arterial embolization reduces rebleeding in non-variceal upper gastrointestinal bleeding: A meta-analysis
Boros, E., Sipos, Z., Hegyi, P., Teutsch, B., Frim, L., Váncsa, S., Kiss, S., Dembrovszky, F., Oštarijaš, E., Shawyer, A., et al
World Journal of Gastroenterology. 2021;27(40):6985-6999
Abstract
BACKGROUND Despite the improvement in the endoscopic hemostasis of non-variceal upper gastrointestinal bleeding (NVUGIB), rebleeding remains a major concern. AIM: To assess the role of prophylactic transcatheter arterial embolization (PTAE) added to successful hemostatic treatment among NVUGIB patients. METHODS We searched three databases from inception through October 19(th), 2020. Randomized controlled trials (RCTs) and observational cohort studies were eligible. Studies compared patients with NVUGIB receiving PTAE to those who did not get PTAE. Investigated outcomes were rebleeding, mortality, reintervention, need for surgery and transfusion, length of hospital (LOH), and intensive care unit (ICU) stay. In the quantitative synthesis, odds ratios (ORs) and weighted mean differences (WMDs) were calculated with the random-effects model and interpreted with 95% confidence intervals (CIs). RESULTS We included a total of 3 RCTs and 9 observational studies with a total of 1329 patients, with 486 in the intervention group. PTAE was associated with lower odds of rebleeding (OR = 0.48, 95%CI: 0.29-0.78). There was no difference in the 30-d mortality rates (OR = 0.82, 95%CI: 0.39-1.72) between the PTAE and control groups. Patients who underwent PTAE treatment had a lower chance for reintervention (OR = 0.48, 95%CI: 0.31-0.76) or rescue surgery (OR = 0.35, 95%CI: 0.14-0.92). The LOH and ICU stay was shorter in the PTAE group, but the difference was non-significant [WMD = -3.77, 95%CI: (-8.00)-0.45; WMD = -1.33, 95%CI: (-2.84)-0.18, respectively]. CONCLUSION PTAE is associated with lower odds of rebleeding and any reintervention in NVUGIB. However, further RCTs are needed to have a higher level of evidence.