31 research outputs found

    Angiotensin II for the Treatment of Vasodilatory Shock

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    BACKGROUND Vasodilatory shock that does not respond to high-dose vasopressors is associated with high mortality. We investigated the effectiveness of angiotensin II for the treatment of patients with this condition. METHODS We randomly assigned patients with vasodilatory shock who were receiving more than 0.2 mu g of norepinephrine per kilogram of body weight per minute or the equivalent dose of another vasopressor to receive infusions of either angiotensin II or placebo. The primary end point was a response with respect to mean arterial pressure at hour 3 after the start of infusion, with response defined as an increase from baseline of at least 10 mm Hg or an increase to at least 75 mm Hg, without an increase in the dose of background vasopressors. RESULTS A total of 344 patients were assigned to one of the two regimens; 321 received a study intervention (163 received angiotensin II, and 158 received placebo) and were included in the analysis. The primary end point was reached by more patients in the angiotensin II group (114 of 163 patients, 69.9%) than in the placebo group (37 of 158 patients, 23.4%) (odds ratio, 7.95; 95% confidence interval [CI], 4.76 to 13.3; P<0.001). At 48 hours, the mean improvement in the cardiovascular Sequential Organ Failure Assessment (SOFA) score (scores range from 0 to 4, with higher scores indicating more severe dysfunction) was greater in the angiotensin II group than in the placebo group (-1.75 vs. -1.28, P = 0.01). Serious adverse events were reported in 60.7% of the patients in the angiotensin II group and in 67.1% in the placebo group. Death by day 28 occurred in 75 of 163 patients (46%) in the angiotensin II group and in 85 of 158 patients (54%) in the placebo group (hazard ratio, 0.78; 95% CI, 0.57 to 1.07; P = 0.12). CONCLUSIONS Angiotensin II effectively increased blood pressure in patients with vasodilatory shock that did not respond to high doses of conventional vasopressors. (Funded by La Jolla Pharmaceutical Company; ATHOS-3 ClinicalTrials.gov number, NCT02338843.)Peer reviewe

    The risk of deterioration in GCS13-15 patients with traumatic brain injury identified by CT imaging : a systematic review and meta-analysis

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    The optimal management of mild traumatic brain injury (TBI) patients with injuries identified by computed tomography (CT) brain scan is unclear. Some guidelines recommend hospital admission for an observation period of at least 24 h. Others argue that selected lower-risk patients can be discharged from the Emergency Department (ED). The objective of our review and meta-analysis was to estimate the risk of death, neurosurgical intervention, and clinical deterioration in mild TBI patients with injuries identified by CT brain scan, and assess which patient factors affect the risk of these outcomes. A systematic review and meta-analysis adhering to PRISMA standards of protocol and reporting were conducted. Study selection was performed by two independent reviewers. Meta-analysis using a random effects model was undertaken to estimate pooled risks for: clinical deterioration, neurosurgical intervention, and death. Meta-regression was used to explore between-study variation in outcome estimates using study population characteristics. Forty-nine primary studies and five reviews were identified that met the inclusion criteria. The estimated pooled risk for the outcomes of interest were: clinical deterioration 11.7% (95% confidence interval [CI]: 11.7%-15.8%), neurosurgical intervention 3.5% (95% CI: 2.2%-4.9%), and death 1.4% (95% CI: 0.8%-2.2%). Twenty-one studies presented within-study estimates of the effect of patient factors. Meta-regression of study characteristics and pooling of within-study estimates of risk factor effect found the following factors significantly affected the risk for adverse outcomes: age, initial Glasgow Coma Scale (GCS), type of injury, and anti-coagulation. The generalizability of many studies was limited due to population selection. Mild TBI patients with injuries identified by CT brain scan have a small but clinically important risk for serious adverse outcomes. This review has identified several prognostic factors; research is needed to derive and validate a usable clinical decision rule so that low-risk patients can be safely discharged from the ED

    On A. Raychaudhuri's paper “electronic energy bands in model three-dimensional lattices”

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    A trial of intrapleural adenoviral-mediated Interferon-α2b gene transfer for malignant pleural mesothelioma.

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    New therapeutic strategies are needed for malignant pleural mesothelioma (MPM). We conducted a single-center, open-label, nonrandomized, pilot and feasibility trial using two intrapleural doses of an adenoviral vector encoding human IFN-α (Ad.IFN-α2b). Nine subjects were enrolled at two dose levels. The first three subjects had very high pleural and systemic IFN-α concentrations resulting in severe flu-like symptoms necessitating dose de-escalation. The next six patients had reduced (but still significant) pleural and serum IFN-α levels, but with tolerable symptoms. Repeated vector administration appeared to prolong IFN-α expression levels. Anti-tumor humoral immune responses against mesothelioma cell lines were seen in seven of the eight subjects evaluated. No clinical responses were seen in the four subjects with advanced disease. However, evidence of disease stability or tumor regression was seen in the remaining five patients, including one dramatic example of partial tumor regression at sites not in contiguity with vector infusion. These data show that Ad.IFN-α2b has potential therapeutic benefit in MPM and that it generates anti-tumor immune responses that may induce anatomic and/or metabolic reductions in distant tumor. Clinical trial registered with www.clinicaltrials.gov (NCT 01212367)
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