SummaryBackgroundAntifibrinolytics reduce death from bleeding in trauma and post-partum haemorrhage. We examined the effect of treatment delay on the effectiveness of antifibrinolytics.MethodsWe did an individual patient-level data meta-analysis of randomised trials done with more than 1000 patients that assessed antifibrinolytics in acute severe bleeding. We identified trials done between Jan 1, 1946, and April 7, 2017, from MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, PubMed, Popline, and the WHO International Clinical Trials Registry Platform. The primary measure of treatment benefit was absence of death from bleeding. We examined the effect of treatment delay on treatment effectiveness using logistic regression models. We investigated the effect of measurement error (misclassification) in sensitivity analyses. This study is registered with PROSPERO, number 42016052155.FindingsWe obtained data for 40 138 patients from two randomised trials of tranexamic acid in acute severe bleeding (traumatic and post-partum haemorrhage). Overall, there were 3558 deaths, of which 1408 (40%) were from bleeding. Most (884 [63%] of 1408) bleeding deaths occurred within 12 h of onset. Deaths from post-partum haemorrhage peaked 2–3 h after childbirth. Tranexamic acid significantly increased overall survival from bleeding (odds ratio [OR] 1·20, 95% CI 1·08–1·33; p=0·001), with no heterogeneity by site of bleeding (interaction p=0·7243). Treatment delay reduced the treatment benefit (p<0·0001). Immediate treatment improved survival by more than 70% (OR 1·72, 95% CI 1·42–2·10; p<0·0001). Thereafter, the survival benefit decreased by 10% for every 15 min of treatment delay until 3 h, after which there was no benefit. There was no increase in vascular occlusive events with tranexamic acid, with no heterogeneity by site of bleeding (p=0·5956). Treatment delay did not modify the effect of tranexamic acid on vascular occlusive events.InterpretationDeath from bleeding occurs soon after onset and even a short delay in treatment reduces the benefit of tranexamic acid administration. Patients must be treated immediately. Further research is needed to deepen our understanding of the mechanism of action of tranexamic acid.FundingUK NIHR Health Technology Assessment programme, Pfizer, BUPA Foundation, and J P Moulton Charitable Foundation (CRASH-2 trial). London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation (WOMAN trial).

Background Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0•9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0•9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124.

Splenic flexure cancers (SFCs) account for up to 8% of all colon cancers (CCs) [1,2]. Although relatively uncommon, the prognosis for SFC is generally poor, with patients often presenting with colonic obstruction, advanced tumour stages and distant metastasis [1-3]. Surgical resection of CC has traditionally been undertaken viaan open approach [1]. Laparoscopic resection, however, has gained popularity, with randomized clinical trials demonstrating superior short-term outcomes (lower pain scores, reduced blood loss and shorter convalescence) and similar long-term oncological outcomes to open surgery [4][5][6]. Laparoscopic resection of SFC is technically demanding due to the steep learning curve associated with the procedure and the complex regional anatomy characterized by the presence of embryological adhesions, proximity to important organs such as the spleen and pancreas, and a highly heterogeneous

Rouvière's sulcus (RS) is increasingly being recognized as an important extra‐biliary landmark during laparoscopic cholecystectomy (LC). The aim of this study was to conduct a systematic analysis of the prevalence and morphological types of RS. A systematic search was conducted through the major databases PubMed, ScienceDirect, Google Scholar, China National Knowledge Infrastructure (CNKI), SciELO, and the Cochrane Library to identify studies eligible for inclusion. The data were extracted and pooled into a random‐effects meta‐analysis using STATA software. The primary and secondary outcomes of the study were the pooled prevalence of RS and its morphological types, respectively. A total of 23 studies (n = 4,495 patients) were included. The overall pooled prevalence of RS was 83% (95% confidence interval [CI] [78, 87]). There were no significant differences in prevalence between cadaveric studies (82%, 95% CI [76, 87]) and laparoscopic studies (83%, 95% CI [77, 88]). The open RS constituted 66% (95% CI [61, 71]) of all cases, while the closed type was present in 34% (95% CI [29, 39]). RS is a relatively constant anatomical structure that can be reliably identified in most patients undergoing cholecystectomy. It can therefore be used as a fixed extra‐biliary landmark for the appropriate site at which to start dissecting during LC to help prevent iatrogenic bile duct injury.

Background: Early administration of the antifibrinolytic drug tranexamic acid reduces death from bleeding in trauma and postpartum haemorrhage. We examined how the effectiveness and safety of antifibrinolytic drugs varies by the baseline risk of death as a result of bleeding. Methods: We performed an individual patient-level data meta-analysis of randomised trials including more than 1000 patients that assessed antifibrinolytics in acute severe bleeding. We identified trials performed between January 1, 1946 and July 5, 2018 (PROSPERO, number 42016052155). Results: Two randomised trials were selected where 28 333 patients received tranexamic acid treatment within 3 h after the onset of acute bleeding. Baseline characteristics to estimate the risk of death as a result of bleeding were divided into four categories: Low (0e5%), intermediate (6e10%), high (11e20%), and very high (>20%). Most patients had a low baseline risk of death as a result of bleeding (23 008 [81%]). Deaths as a result of bleeding occurred in all baseline risk categories with 240 (1%), 202 (8%), 232 (14%), and 357 (30%) deaths in the low-, intermediate-, high-, and very high-risk categories, respectively. The effectiveness of tranexamic acid did not vary by baseline risk when given within 3 h after bleeding onset (P¼0.51 for interaction term). There was no increased risk of vascular occlusive events with tranexamic acid and it did not vary by baseline risk categories (P¼0.25). Conclusions: Tranexamic acid appears to be safe and effective regardless of baseline risk of death. Because many deaths are in patients at low and intermediate risk, tranexamic acid use should not be restricted to the most severely injured or bleeding patients.