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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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Diagnostic and therapeutic yields of early capsule endoscopy and device-assisted enteroscopy in the setting of overt GI bleeding: a systematic review with meta-analysis
Estevinho, M. M., Pinho, R., Fernandes, C., Rodrigues, A., Ponte, A., Gomes, A. C., Afecto, E., Correia, J., Carvalho, J.
Gastrointestinal Endoscopy. 2022;95(4):610-625.e9
Abstract
BACKGROUND AND AIMS Small-bowel capsule endoscopy (SBCE) and device-assisted enteroscopy (DAE) are essential in obscure GI bleeding (OGIB) management. However, the best timing for such procedures remains unknown. This meta-analysis aimed to compare, for the first time, diagnostic and therapeutic yields, detection of active bleeding and vascular lesions, recurrent bleeding, and mortality of "early" versus "nonearly" SBCE and DAE. METHODS MEDLINE, ScienceDirect, and Cochrane Central Register of Controlled Trials were searched to identify studies comparing early versus nonearly SBCE and DAE. Random-effects meta-analysis was performed; reporting quality was assessed. RESULTS From 1974 records, 39 were included (4825 patients). Time intervals for the early approach varied, within 14 days in SBCE and 72 hours in DAE. The pooled diagnostic and therapeutic yields of early DAE were superior to those of SBCE (7.97% and 20.89%, respectively; P < .05). The odds for active bleeding (odds ratio [OR], 5.09; I(2) = 53%), positive diagnosis (OR, 3.99; I(2) = 45%), and therapeutic intervention (OR, 3.86; I(2) = 67%) were higher in the early group for SBCE and DAE (P < .01). Subgroup effects in diagnostic yield were only identified for the early group sample size. Our study failed to identify differences when studies were classified according to time intervals for early DAE (I(2) < 5%), but the analysis was limited because of a lack of data availability. Lower recurrent bleeding in early SBCE and DAE was observed (OR, .40; P < .01; I(2) = 0%). CONCLUSIONS The role of small-bowel studies in the early evaluation of OGIB is unquestionable, impacting diagnosis, therapeutic intervention, and prognosis. Comparative studies are still needed to identify optimal timing.
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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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Plasmapheresis compared with conventional treatment for hypertriglyceridemia-induced acute pancreatitis: A systematic review and meta-analysis
Yan LH, Hu XH, Chen RX, Pan MM, Han YC, Gao M, Liu H
Journal of clinical apheresis. 2022
Abstract
BACKGROUND The treatment of acute pancreatitis (AP) induced by hypertriglyceridemia (HTG) remains controversial with regard to plasmapheresis vs conventional treatment. We reviewed relevant articles to explore the efficacy of plasmapheresis in the management of HTG-induced AP. METHODS We systematically reviewed studies that compared plasmapheresis with conventional treatment for HTG-induced AP using three databases: PubMed, Embase, and Cochrane Library, as well as relevant references. The primary outcomes were 24 h triglyceride reduction rate and in-hospital mortality. RESULTS A total of 791 articles were retrieved. Finally, 15 observational studies (1080 participants) were included, most of which were historical cohort studies. Compared with conventional treatment, plasmapheresis assisted in the reduction of serum triglyceride (TG) levels in the first 24 h after hospital admission (standardized mean difference [SMD]: 0.58; 95% confidence interval [CI]: 0.17 to 0.99; P = 0.005). However, it resulted in increased hospitalization costs (thousand yuan) (weighted mean difference [WMD]: 24.32; 95% CI: 12.96 to 35.68; P < 0.001). With regard to in-hospital mortality, although the mortality rate in the plasmapheresis group was higher than that in the conventional treatment group (relative risk [RR]: 1.74; 95% CI: 1.03 to 2.94; P = 0.038), the result was disturbed by confounding factors as per the subgroup and sensitivity analysis, as well as trial sequential analysis (TSA). No significant differences were found in other outcomes, including systematic complications, local complications, the requirement for surgery, and hospitalization duration. CONCLUSION The effect of plasmapheresis in HTG-induced AP is not superior to that of conventional treatment, even resulting in a greater economic burden to patients and health care system. High quality randomized control trials are required to obtain a more a definitive understanding of this issue.
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Apheresis Technique for Acute Hyperlipidemic Pancreatitis: A Systemic Review and Meta-Analysis
Lin YF, Yao Y, Xu Y, Huang HB
Digestive diseases and sciences. 2022
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Abstract
BACKGROUND The apheresis technique is increasingly used in patients with hypertriglyceridemia-induced pancreatitis (HTGP), while its role in this context is still not well established. Thus, we aimed to evaluate the clinical outcomes of an apheresis therapy compared to usual care in such a patient population. METHODS We searched PubMed, Embase, and Cochrane library databases up to July 10, 2021. Studies were included if they focused on HTGP treated with or without apheresis technique. We used the Newcastle-Ottawa Scale to assess the quality of the included studies. The primary outcome was the mortality rate. We also explored the heterogeneity, sensitivity analysis, subgroup analysis, and publication bias. RESULTS Sixteen observational studies with 1476 adults were included. The overall quality of included studies was moderate. Despite better TG level reduction with apheresis therapy (mean difference [MD], 12.27 mmol/L, 95% CI, 3.74 to 20.81; I(2) = 78%; P = 0.005), use of apheresis did not reduce the mortality (odds ratio [OR], 1.01; 95% CI, 0.65 to 1.59; P = 0.95) compared with usual care. This result was further confirmed by sensitivity analysis, subgroup analysis. The length of stay in hospital (MD, 0.96 days; 95% CI, - 1.22 to 3.14; I(2) = 70%; P = 0.39) and most complications were similar between the groups, while hospital cost was significantly higher in the apheresis group. CONCLUSIONS The apheresis technique did not decrease the mortality in HTGP patients compared with usual care. Until the results of high-quality RCTs are known, these findings do not support the routine use of the apheresis technique in such a patient population.
PICO Summary
Population
Patients with hypertriglyceridemia-induced pancreatitis, (16 studies, n= 1,476).
Intervention
Apheresis therapy.
Comparison
Usual care.
Outcome
Despite better triglycerides level reduction with apheresis therapy (mean difference [MD], 12.27 mmol/L), use of apheresis did not reduce the mortality compared with usual care. The length of stay in hospital (MD, 0.96 days) and most complications were similar between the groups, while hospital cost was significantly higher in the apheresis group. The overall quality of included studies was moderate.
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Role of routine second-look endoscopy in patients with acute peptic ulcer bleeding: meta-analysis of randomized controlled trials
Kamal, F., Khan, M. A., Lee-Smith, W., Sharma, S., Imam, Z., Henry, C., Jowhar, D., Khan, Z., Petryna, E., Iqbal, U., et al
Gastrointestinal Endoscopy. 2021;93(6):1228-1237.e5
Abstract
BACKGROUND AND AIMS Studies evaluating the role of routine second-look endoscopy in patients with acute upper GI bleed because of peptic ulcer disease (PUD) have reported conflicting results. This meta-analysis evaluates the usefulness of routine second-look endoscopy in these patients. METHODS We reviewed several databases from inception to September 15, 2020 to identify randomized controlled trials (RCTs) that compared routine second-look endoscopy with no planned second-look endoscopy in patients with acute upper GI bleed because of PUD. Our outcomes of interest were recurrent bleeding, mortality, need for surgery, and mean number of units of blood transfused. For categorical variables, we calculated pooled risk ratios (RRs) with 95% confidence intervals (CIs); for continuous variables, we calculated standardized mean difference with 95% CIs. Data were analyzed using a random effects model. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework to ascertain the quality of evidence. RESULTS We included 9 RTCs comprising 1452 patients; 726 patients underwent planned/routine second-look endoscopy and 726 did not. We found no significant difference in recurrent bleeding (RR, .79; 95% CI, .51-1.23), need for surgery (RR, .58; 95% CI, .29-1.15), mortality (RR, .69; 95% CI, .33-1.45), or mean number of units of blood transfused (standardized mean difference, -.06; 95% CI, -.19 to .07). Quality of evidence ranged from low to moderate based on the GRADE framework. CONCLUSIONS Single endoscopy with complete endoscopic hemostasis is not inferior to routine second-look endoscopy in reducing the risk of recurrent bleeding, mortality, or need for surgery in patients with acute upper GI bleed because of PUD.
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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.