Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial

Background Tranexamic acid reduces surgical bleeding and decreases mortality in patients with traumatic extracranial bleeding. Intracranial bleeding is common after traumatic brain injury (TBI) and can cause brain herniation and death. We aimed to assess the effects of tranexamic acid in patients with TBI. Methods This randomised, placebo-controlled trial was done in 175 hospitals in 29 countries. Adults with TBI who were within 3 h of injury, had a Glasgow Coma Scale (GCS) score of 12 or lower or any intracranial bleeding on CT scan, and no major extracranial bleeding were eligible. The time window for eligibility was originally 8 h but in 2016 the protocol was changed to limit recruitment to patients within 3 h of injury. This change was made blind to the trial data, in response to external evidence suggesting that delayed treatment is unlikely to be effective. We randomly assigned (1:1) patients to receive tranexamic acid (loading dose 1 g over 10 min then infusion of 1 g over 8 h) or matching placebo. Patients were assigned by selecting a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was head injury-related death in hospital within 28 days of injury in patients treated within 3 h of injury. We prespecified a sensitivity analysis that excluded patients with a GCS score of 3 and those with bilateral unreactive pupils at baseline. All analyses were done by intention to treat. This trial was registered with ISRCTN (ISRCTN15088122), ClinicalTrials.gov (NCT01402882), EudraCT (2011-003669-14), and the Pan African Clinical Trial Registry (PACTR20121000441277). Results Between July 20, 2012, and Jan 31, 2019, we randomly allocated 12 737 patients with TBI to receive tranexamic acid (6406 [50·3%] or placebo [6331 [49·7%], of whom 9202 (72·2%) patients were treated within 3 h of injury. Among patients treated within 3 h of injury, the risk of head injury-related death was 18·5% in the tranexamic acid group versus 19·8% in the placebo group (855 vs 892 events; risk ratio [RR] 0·94 [95% CI 0·86-1·02]). In the prespecified sensitivity analysis that excluded patients with a GCS score of 3 or bilateral unreactive pupils at baseline, the risk of head injury-related death was 12·5% in the tranexamic acid group versus 14·0% in the placebo group (485 vs 525 events; RR 0·89 [95% CI 0·80-1·00]). The risk of head injury-related death reduced with tranexamic acid in patients with mild-to-moderate head injury (RR 0·78 [95% CI 0·64-0·95]) but not in patients with severe head injury (0·99 [95% CI 0·91-1·07]; p value for heterogeneity 0·030). Early treatment was more effective than was later treatment in patients with mild and moderate head injury (p=0·005) but time to treatment had no obvious effect in patients with severe head injury (p=0·73). The risk of vascular occlusive events was similar in the tranexamic acid and placebo groups (RR 0·98 (0·74-1·28). The risk of seizures was also similar between groups (1·09 [95% CI 0·90-1·33]). Interpretation Our results show that tranexamic acid is safe in patients with TBI and that treatment within 3 h of injury reduces head injury-related death. Patients should be treated as soon as possible after injury. Funding National Institute for Health Research Health Technology Assessment, JP Moulton Charitable Trust, Department of Health and Social Care, Department for International Development, Global Challenges Research Fund, Medical Research Council, and Wellcome Trust (Joint Global Health Trials scheme)

Hepatoprotective activity of hydroalcoholic extract of leaves of <i style="">Alocasia indica</i> (Linn.)<i style=""></i>

816-821Oral administration of hydroalcoholic extract of A. indica (250 and 500 mg/kg) effectively inhibited CCl4 and paracetamol induced changes in the serum marker enzymes, cholesterol, serum protein and albumin in a dose-dependent manner as compared to the normal and the standard drug silymarin-treated groups. Hepatic steatosis, fatty infiltration, hydropic degeneration and necrosis observed in CCl4 and paracetamol-treated groups were completely absent in histology of the liver sections of the animals treated with the extracts. The results suggests that the hydroalcoholic extract of leaves of A. indica possess significant potential as hepatoprotective agent.</b

Acute coronary syndrome in patients with prior coronary artery bypass surgery: observations from a 20-year registry in a middle-eastern country.

OBJECTIVES: Clinical characteristics and trends in the outcome of acute coronary syndrome (ACS) in patients with prior coronary artery bypass graft surgery (CABG) are unclear. The aim of this study was to evaluate clinical characteristics, in-hospital treatment, and outcomes in patients presented with ACS with or without a history of prior CABG over 2 decades. METHODS: Data were derived from hospital-based study for collected data from 1991 through 2010 of patients hospitalized with ACS in Doha, Qatar. Data were analyzed according to their history of prior CABG. Baseline clinical characteristics, in-hospital treatment, and outcome were compared. RESULTS: A total 16,750 consecutive patients with ACS were studied, of which 693 (4.1%) had prior CABG. Patients with prior CABG were older (mean 60.5±11 vs. 53±12 years; P = 0.001), more likely to be females and have more cardiovascular risk factors than the non-CABG group. Prior CABG patients had larger infarct size, were less likely to receive reperfusion therapy, early invasive therapy and more likely to receive evidence-based therapies when compared to non-CABG patients. In-hospital mortality and stroke rates were comparable between the 2 groups. Over 2 decades, there was reduction in the in-hospital mortality rates and stroke rates in both groups (CABG, death; 13.2% to 4%, stroke; 1.9% to 0.0%, non-CABG, death; 10% to 3.2%, stroke 1.0% to 0.1%; all, p = 0.001). CONCLUSION: Significant reduction in-hospital morbidity and mortality among ACS patients with prior CABG over a 20-year period

The 20-year trend of medications prescribed during admission in patient with acute coronary syndrome.

<p>Data are expressed in numbers (%) of patients. Same abbreviations mentioned in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0040571#pone-0040571-t002" target="_blank">table 2</a>.</p

The predictors of in-hospital mortality in patients with prior coronary artery bypass surgery who presented with acute coronary syndrome.

<p>CABG  =  coronary artery bypass graft; ACS  =  acute coronary syndrome; ACE  =  angiotensin-converting enzyme; ARB  =  angiotensin receptor blocker; LMWH  =  low molecular weight heparin.</p

Targeting the adaptability of heterogeneous aneuploids

SummaryAneuploid genomes, characterized by unbalanced chromosome stoichiometry (karyotype), are associated with cancer malignancy and drug resistance of pathogenic fungi. The phenotypic diversity resulting from karyotypic diversity endows the cell population with superior adaptability. We show here, using a combination of experimental data and a general stochastic model, that the degree of phenotypic variation, thus evolvability, escalates with the degree of overall growth suppression. Such scaling likely explains the challenge of treating aneuploidy diseases with a single stress-inducing agent. Instead, we propose the design of an “evolutionary trap” (ET) targeting both karyotypic diversity and fitness. This strategy entails a selective condition “channeling” a karyotypically divergent population into one with a predominant and predictably drugable karyotypic feature. We provide a proof-of-principle case in budding yeast and demonstrate the potential efficacy of this strategy toward aneuploidy-based azole resistance in Candida albicans. By analyzing existing pharmacogenomics data, we propose the potential design of an ET against glioblastoma

Multivariate analysis of predictors of in-hospital mortality in patients presented with acute coronary syndromes.

<p>CABG  =  coronary artery bypass graft; LMWH  =  low molecular weight heparin; ACE =  angiotension converting enzyme, ARB  =  angiotensin receptor blocker; CI  =  confident interval.</p

The 20 years trend of mortality in 16,750 patients with acute coronary syndrome with or without history of prior coronary artery bypass surgery.

<p>CABG  =  coronary artery bypass graft; ACS  =  acute coronary syndrome.</p

Medication received before, during admission and at discharge in acute coronary syndrome patients with or without prior coronary artery bypass surgery.

<p>Data are expressed in numbers (%) of patients.CABG  =  coronary artery bypass graft; HMG-CoA  =  hydroxy methyl glutaryl-coenzyme A; GP  =  glycoprotein; LMWH  =  low molecular weight heparin; CCB  =  calcium channel blockers; ACE = angiotension converting enzyme inhibitor, ARB = angiotensin receptor blocker.</p