Identifying differentially expressed genes between experimental conditions is still the gold-standard approach to interpret transcriptomic profiles. Alternative approaches based on diversity measures ...have been proposed to complement the interpretation of such datasets but are only used marginally.
Here, we reinvestigated diversity measures, which are commonly used in ecology, to characterize mice pregnancy microenvironments based on a public transcriptome dataset. Mainly, we evaluated the Tsallis entropy function to explore the potential of a collection of diversity measures for capturing relevant molecular event information.
We demonstrate that the Tsallis entropy function provides additional information compared to the traditional diversity indices, such as the Shannon and Simpson indices. Depending on the relative importance given to the most abundant transcripts based on the Tsallis entropy function parameter, our approach allows appreciating the impact of biological stimulus on the inter-individual variability of groups of samples. Moreover, we propose a strategy for reducing the complexity of transcriptome datasets using a maximation of the beta diversity.
We highlight that a diversity-based analysis is suitable for capturing complex molecular events occurring during physiological events. Therefore, we recommend their use through the Tsallis entropy function to analyze transcriptomics data in addition to differential expression analyses.
Microcirculatory dysfunction has been well reported in clinical studies in septic shock. However, no clinical studies have investigated microcirculatory blood flow behavior in hemorrhagic shock. The ...main objective of this study was to assess the time course of sublingual microcirculation in traumatic hemorrhagic shock during the first 4 days after trauma.
Prospective observational study.
Eighteen traumatic hemorrhagic shock patients.
The sublingual microcirculation was estimated at the study inclusion after surgical or angiographic embolization to control bleeding (D1), and then three times at 24-hour intervals (D2, D3, and D4).
Sublingual microcirculation was impaired for 72 hours despite restoration of the macrovascular circulation after control of bleeding in traumatic hemorrhagic shock patients. Furthermore, we found significantly higher decreases in the microvascular flow index and proportion of perfused vessels in high Sequential Organ Failure Assessment score patients at D4 (Sequential Organ Failure Assessment score ≥ 6) compared to low Sequential Organ Failure Assessment score patients at D4 (Sequential Organ Failure Assessment score < 6) without any differences in global hemodynamics between these two groups. Finally, the initial proportion of perfused vessels at D1 appears to be a good predictor of high Sequential Organ Failure Assessment score at D4.
Alterations of microcirculation in traumatic hemorrhagic shock patients result from the interplay among hemorrhage-induced tissue hypoperfusion, trauma injuries, inflammatory response, and subsequent resuscitation interventions. Despite restoration of the macrocirculation, the sublingual microcirculation was impaired for at least 72 hours. The initial proportion of perfused vessels appears to be a good predictor of high Sequential Organ Failure Assessment score at D4. Further studies are required to firmly establish the link between microvascular alterations and organ dysfunction in traumatic hemorrhagic shock patients.
Summary Background The clinical benefit of preventive eradication of unruptured brain arteriovenous malformations remains uncertain. A Randomised trial of Unruptured Brain Arteriovenous malformations ...(ARUBA) aims to compare the risk of death and symptomatic stroke in patients with an unruptured brain arteriovenous malformation who are allocated to either medical management alone or medical management with interventional therapy. Methods Adult patients (≥18 years) with an unruptured brain arteriovenous malformation were enrolled into this trial at 39 clinical sites in nine countries. Patients were randomised (by web-based system, in a 1:1 ratio, with random permuted block design block size 2, 4, or 6, stratified by clinical site) to medical management with interventional therapy (ie, neurosurgery, embolisation, or stereotactic radiotherapy, alone or in combination) or medical management alone (ie, pharmacological therapy for neurological symptoms as needed). Patients, clinicians, and investigators are aware of treatment assignment. The primary outcome is time to the composite endpoint of death or symptomatic stroke; the primary analysis is by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00389181. Findings Randomisation was started on April 4, 2007, and was stopped on April 15, 2013, when a data and safety monitoring board appointed by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health recommended halting randomisation because of superiority of the medical management group (log-rank Z statistic of 4·10, exceeding the prespecified stopping boundary value of 2·87). At this point, outcome data were available for 223 patients (mean follow-up 33·3 months SD 19·7), 114 assigned to interventional therapy and 109 to medical management. The primary endpoint had been reached by 11 (10·1%) patients in the medical management group compared with 35 (30·7%) in the interventional therapy group. The risk of death or stroke was significantly lower in the medical management group than in the interventional therapy group (hazard ratio 0·27, 95% CI 0·14–0·54). No harms were identified, other than a higher number of strokes (45 vs 12, p<0·0001) and neurological deficits unrelated to stroke (14 vs 1, p=0·0008) in patients allocated to interventional therapy compared with medical management. Interpretation The ARUBA trial showed that medical management alone is superior to medical management with interventional therapy for the prevention of death or stroke in patients with unruptured brain arteriovenous malformations followed up for 33 months. The trial is continuing its observational phase to establish whether the disparities will persist over an additional 5 years of follow-up. Funding National Institutes of Health, National Institute of Neurological Disorders and Stroke.
Summary Background Optimum duration of dual antiplatelet treatment (DAPT) after coronary stenting remains uncertain, with an unknown efficacy to safety ratio of extended treatment leading to ...discrepancies between international guidelines and clinical practice. We assessed whether DAPT continuation beyond 1 year after coronary stenting is beneficial. Methods This analysis was a planned extension of the previously published ARCTIC-Monitoring trial, in which we randomly allocated 2440 patients to a strategy of platelet function testing with antiplatelet treatment adjustment or a conventional strategy after coronary stenting with drug-eluting stent (DES). We recruited patients (aged 18 years or older) scheduled for planned DES implantation at 38 centres in France. After 1 year of follow-up, patients without contraindication to interruption of DAPT were eligible for a second randomisation to this second phase of the study (ARCTIC-Interruption). Using a computer-generated randomisation sequence (1:1; stratified by centre), we allocated patients to a strategy of interruption of DAPT where the thienopyridine was interrupted and single aspirin antiplatelet treatment was maintained (interruption group) or a strategy of DAPT continuation for 6–18 months (continuation group). The primary endpoint was the composite of death, myocardial infarction, stent thrombosis, stroke, or urgent revascularisation, analysed by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00827411. Findings Between Jan 4, 2011, and March 3, 2012, 1259 eligible patients were randomly allocated to treatment in ARCTIC-Interruption: 624 to the interruption group and 635 to the continuation group. After a median follow-up of 17 months (IQR 15–18), the primary endpoint occurred in 27 (4%) patients in the interruption group and 24 (4%) patients in the continuation group (hazard ratio HR 1·17 95% CI 0·68–2·03; p=0·58). STEEPLE major bleeding events occurred more often in the continuation group (seven 1% patients) compared with the interruption group (one <0·5% patient; HR 0·15 0·02–1·20; p=0·073). Major or minor bleedings were also more common in the continuation group compared with the interruption group (12 2% patients vs three 1% patients; HR 0·26 0·07–0·91; p=0·04). Interpretation Our finding suggests no apparent benefit but instead harm with extension of DAPT beyond 1 year after stenting with DES when no event has occurred within the first year after stenting. No conclusion can be drawn for high-risk patients who could not be randomised. The consistency between findings from all trials of such interruption suggests the need for a reappraisal of guidelines for DAPT after coronary stenting towards shorter duration of treatment. Funding Allies in Cardiovascular Trials Initiatives and Organized Networks (ACTION Study Group), Fondation de France, Sanofi-Aventis, Cordis, Medtronic, Boston Scientific, Fondation SGAM.
The impact of continuous venovenous hemofiltration on sepsis-induced multiple organ failure severity is controversial. We sought to assess the effect of early application of hemofiltration on the ...degree of organ dysfunction and plasma cytokine levels in patients with severe sepsis or septic shock.
Prospective, randomized, open, multicenter study setting, 12 French intensive care units.
A total of 80 patients were enrolled within 24 hours of development of the first organ failure related to a new septic insult.
Patients were randomized to group 1 (HF), who received hemofiltration (25 mL/kg/hr) for a 96-hour period, or group 2 (C) who were managed conventionally.
The primary end point was the number, severity, and duration of organ failures during 14 days, as evaluated by the Sepsis-Related Organ Failure Assessment score, on an intention-to-treat analysis. Strict guidelines were provided to perform continuous hemofiltration under the same conditions and bearing the same objectives in all centers. Because of inclusion stagnation, the trial was discontinued after an interim analysis by which time 76 patients had been randomized. The number and severity of organ failures were significantly higher in the HF group (p < 0.05). No modifications in plasma cytokine levels could be detected.
These data suggest that early application of standard continuous venovenous hemofiltration is deleterious in severe sepsis and septic shock. This study does not rule out an effect of high-volume hemofiltration (>35 mL/kg/hr) on the course of sepsis.
Abstract
Erythrocyte aggregation kinetics is accelerated in diseases with a strong inflammation component. This study aimed to evaluate whether, in an emergency setting, a new point-of-care test ...measuring erythrocyte aggregation kinetics (EAK) can identify patients with underlying inflammation. Patients visiting an emergency department and needing a blood exam were successively included. EAK was measured at the point-of-care in 20 s directly on the blood samples collected in regular tubes without any manipulation. The primary measure was EAK’s half-life during the first 5 s (EAK5s). Each patient’s inflammation status was assessed blind to the EAK test results. Receiver Operating Characteristic (ROC) curves for inflammation status were built. 268 patients had their EAK5s measured, and a clear inflammation status was determined for 214 patients (65 had inflammation). Mean EAK5s were 2.18 s and 1.75 s for no inflammation and inflammation groups respectively (p < 0.001). EAK5s appears to be a better inflammation marker than C-Reactive protein (CRP), with an area under the ROC curve of 0.845 compared to 0.806 for CRP (p < 0.0001). The Youden threshold for prediction of inflammation was 1.86 s with 84.6% (78.5–89.9%) specificity and 70.8% (60–81.5%) sensitivity. Point-of-care EAK is an easily measured, immediately available marker of inflammation with a better predictive power than CRP’s.
Background & Aims: The purpose of our study was to prospectively compare the success rate and diagnostic accuracy of magnetic resonance elastography, ultrasound elastography, and aspartate ...aminotransferase to platelets ratio index (APRI) measurements for the noninvasive staging of fibrosis in patients with chronic liver disease. Methods: We performed a prospective blind comparison of magnetic resonance elastography, ultrasound elastography, and APRI in a consecutive series of patients who underwent liver biopsy for chronic liver disease in a university-based hospital. Histopathologic staging of liver fibrosis according to the METAVIR scoring system served as the reference. Results: A total of 141 patients were assessed. The technical success rate of magnetic resonance elastography was higher than that of ultrasound elastography (133/141 94% vs 118/141 84%; P = .016). Magnetic and ultrasound elastography, APRI measurements, and histopathologic analysis of liver biopsy specimens were technically successful in 96 patients. The areas under the receiver operating characteristic curves of magnetic resonance elasticity (0.994 for F ≥ 2; 0.985 for F ≥ 3; 0.998 for F = 4) were larger ( P < .05) than those of ultrasound elasticity, APRI, and the combination of ultrasound elasticity and APRI (0.837, 0.709, and 0.849 for F ≥ 2; 0.906, 0.816, and 0.936 for F ≥ 3; 0.930, 0.820, and 0.944 for F = 4, respectively). Conclusions: Magnetic resonance elastography has a higher technical success rate than ultrasound elastography and a better diagnostic accuracy than ultrasound elastography and APRI for staging liver fibrosis.
Summary Background Malignant infarction of the middle cerebral artery (MCA) is associated with an 80% mortality rate. Non-randomised studies have suggested that decompressive surgery reduces this ...mortality without increasing the number of severely disabled survivors. To obtain sufficient data as soon as possible to reliably estimate the effects of decompressive surgery, results from three European randomised controlled trials (DECIMAL, DESTINY, HAMLET) were pooled. The trials were ongoing when the pooled analysis was planned. Methods Individual data for patients aged between 18 years and 60 years, with space-occupying MCA infarction, included in one of the three trials, and treated within 48 h after stroke onset were pooled for analysis. The protocol was designed prospectively when the trials were still recruiting patients and outcomes were defined without knowledge of the results of the individual trials. The primary outcome measure was the score on the modified Rankin scale (mRS) at 1 year dichotomised between favourable (0–4) and unfavourable (5 and death) outcome. Secondary outcome measures included case fatality rate at 1 year and a dichotomisation of the mRS between 0–3 and 4 to death. Data analysis was done by an independent data monitoring committee. Findings 93 patients were included in the pooled analysis. More patients in the decompressive-surgery group than in the control group had an mRS≤4 (75% vs 24%; pooled absolute risk reduction 51% 95% CI 34–69), an mRS≤3 (43% vs 21%; 23% 5–41), and survived (78% vs 29%; 50% 33–67), indicating numbers needed to treat of two for survival with mRS≤4, four for survival with mRS≤3, and two for survival irrespective of functional outcome. The effect of surgery was highly consistent across the three trials. Interpretation In patients with malignant MCA infarction, decompressive surgery undertaken within 48 h of stroke onset reduces mortality and increases the number of patients with a favourable functional outcome. The decision to perform decompressive surgery should, however, be made on an individual basis in every patient.
This open-label, randomized, and multicentre trial tested the hypothesis that, on a background of aspirin, continuing clopidogrel would be superior to stopping clopidogrel at 12 months following ...drug-eluting stent (DES) implantation.
Patients (N = 1799) who had undergone placement of ≥1 DES for stable coronary artery disease or acute coronary syndrome were included in 58 French sites (January 2009-January 2013). Patients (N = 1385) free of major cardiovascular/cerebrovascular events or major bleeding and on aspirin and clopidogrel 12 months after stenting were eligible for randomization (1:1) between continuing clopidogrel 75 mg daily (extended-dual antiplatelet therapy, DAPT, group) or discontinuing clopidogrel (aspirin group). The primary outcome was net adverse clinical events defined as the composite of death, myocardial infarction, stroke, or major bleeding. Follow-up was planned from a minimum of 6 to a maximum of 36 months after randomization. Owing to slow recruitment, the study was stopped after enrolment of 1385 of a planned 1966 patients. Median follow-up after stenting was 33.4 months. The primary outcome occurred in 40 patients (5.8%) in the extended-DAPT group and 52 in the aspirin group (7.5%; hazard ratio 0.75, 95% confidence interval 0.50-1.28; P = 0.17). Rates of death were 2.3% in the extended-DAPT group and 3.5% in the aspirin group (HR 0.65, 95% CI 0.34-1.22; P = 0.18). Rates of major bleeding were identical (2.0%, P = 0.95).
Extended DAPT did not achieve superiority in reducing net adverse clinical events compared to 12 months of DAPT after DES placement. The power of the OPTIDUAL trial was however low and reduced by premature termination of enrolment.
NCT00822536.
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