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Still cooling after all these years: Meta-analysis of pre-clinical trials of therapeutic hypothermia for acute ischemic stroke.

ABSTRACT: Therapeutic hypothermia is the most potent neuroprotectant for experimental cerebral ischemia, illustrated in a 2007 meta-analysis published in this journal. To address recent therapeutic nihilism, we systematically reviewed recent experimental literature. Quality scoring showed considerable improvement in study design. Using several outcome measures in a variety of models and species, therapeutic hypothermia was protective compared with normothermia, with powerful and statistically significant normalized treatment effect sizes, in 60 papers comprising 216 comparisons. In the past 5 years, preclinical studies of ischemic stroke re-emphasize that therapeutic hypothermia is potently effective, justifying further development in larger human clinical trials.

SUBMITTER: Dumitrascu OM

PROVIDER: S-EPMC4929706 | biostudies-other | 2016 Jul

REPOSITORIES: biostudies-other

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Still cooling after all these years: Meta-analysis of pre-clinical trials of therapeutic hypothermia for acute ischemic stroke.

Dumitrascu Oana M OM Lamb Jessica J Lyden Patrick D PD

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20160418 7

Therapeutic hypothermia is the most potent neuroprotectant for experimental cerebral ischemia, illustrated in a 2007 meta-analysis published in this journal. To address recent therapeutic nihilism, we systematically reviewed recent experimental literature. Quality scoring showed considerable improvement in study design. Using several outcome measures in a variety of models and species, therapeutic hypothermia was protective compared with normothermia, with powerful and statistically significant ...[more]

PMID: 27089911

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Project description:BackgroundHypoxic perinatal brain injury is caused by lack of oxygen to baby's brain and can lead to death or permanent brain damage. However, the effectiveness of therapeutic hypothermia in birth asphyxiated infants with encephalopathy is uncertain. This systematic review and meta-analysis was aimed to estimate the pooled relative risk of mortality among birth asphyxiated neonates with hypoxic-ischemic encephalopathy in a global context.MethodsWe used the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines to search randomized control trials from electronic databases (PubMed, Cochrane library, Google Scholar, MEDLINE, Embase, Scopus, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and meta register of Current Controlled Trials (mCRT)). The authors extracted the author's name, year of publication, country, method of cooling, the severity of encephalopathy, the sample size in the hypothermic, and non-hypothermic groups, and the number of deaths in the intervention and control groups. A weighted inverse variance fixed-effects model was used to estimate the pooled relative risk of mortality. The subgroup analysis was done by economic classification of countries, methods of cooling, and cooling devices. Publication bias was assessed with a funnel plot and Eggers test. A sensitivity analysis was also done.ResultsA total of 28 randomized control trials with a total sample of 35, 92 (1832 hypothermic 1760 non-hypothermic) patients with hypoxic-ischemic encephalopathy were used for the analysis. The pooled relative risk of mortality after implementation of therapeutic hypothermia was found to be 0.74 (95%CI; 0.67, 0.80; I2 = 0.0%; p<0.996). The subgroup analysis revealed that the pooled relative risk of mortality in low, low middle, upper-middle and high income countries was 0.32 (95%CI; -0.95, 1.60; I2 = 0.0%; p<0.813), 0.5 (95%CI; 0.14, 0.86; I2 = 0.0%; p<0.998), 0.62 (95%CI; 0.41-0.83; I2 = 0.0%; p<0.634) and 0.76 (95%CI; 0.69-0.83; I2 = 0.0%; p<0.975) respectively. The relative risk of mortality was the same in selective head cooling and whole-body cooling method which was 0.74. Regarding the cooling device, the pooled relative risk of mortality is the same between the cooling cap and cooling blanket (0.74). However, it is slightly lower (0.73) in a cold gel pack.ConclusionsTherapeutic hypothermia reduces the risk of death in neonates with moderate to severe hypoxic-ischemic encephalopathy. Both selective head cooling and whole-body cooling method are effective in reducing the mortality of infants with this condition. Moreover, low income countries benefit the most from the therapy. Therefore, health professionals should consider offering therapeutic hypothermia as part of routine clinical care to newborns with hypoxic-ischemic encephalopathy especially in low-income countries.

Project description:BackgroundThe current guideline recommended the use of intravenous thrombolysis (IVT) before Endovascular thrombectomy (EVT), but the effectiveness and safety of tenecteplase compare to alteplase in patients before EVT remain uncertain.MethodsWe searched PubMed, Embase, Web of Science, and the Cochrane Library to identify eligible articles from inception until September 16, 2023. The primary outcome was functional independence (mRS 0-2) at 90 days. Secondary outcomes included excellent outcome (mRS 0-1) at 90 days, all-cause mortality at follow-up, successful reperfusion (TICI 2b-3) after the end of EVT, symptomatic intracranial hemorrhage (sICH) or any intracranial hemorrhage (aICH). The PROSPERO registration number is CRD42023470419.ResultsEight randomized controlled trials (RCTs) were included involving 2,836 acute ischemic stroke (AIS) patients. Compared to EVT alone, tenecteplase (0.25 mg/kg and 0.4 mg/kg) + EVT and 0.9 mg/kg alteplase + EVT were significant difference associated with higher successful reperfusion (TICI 2b-3) after the end of EVT (RR = 2.31; 95% CI 1.15-4.63; RR = 2.31; 95% CI 1.00-5.33; RR = 1.05; 95% CI 1.01-1.09). And compared to 0.25 mg/kg tenecteplase + EVT, alteplase (0.6 mg/kg and 0.9 mg/kg) + EVT were significant difference associated with lower successful reperfusion (TICI 2b-3) after the end of EVT (RR = 0.45; 95% CI 0.22-0.90; RR = 0.45; 95% CI 0.23-0.91). The risk of aICH (RR = 1.50; 95% CI 1.07-2.09) was significantly higher for 0.6 mg/kg alteplase + EVT than EVT alone. There was no significant difference in functional independence (mRS 0-2), excellent outcome (mRS 0-1), all-cause mortality or sICH among the different IVT strategies (0.25 mg/kg or 0.4 mg/kg tenecteplase and 0.6 mg/kg or 0.9 mg/kg alteplase) before EVT.ConclusionThe use of alteplase before EVT may potentially improve the successful reperfusion after EVT compared to tenecteplase. Due to the insufficient sample size, more high-quality RCTs are needed to confirm effectiveness and safety of tenecteplase compare to alteplase in patients before EVT.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier: CRD42023470419.

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Still cooling after all these years: Meta-analysis of pre-clinical trials of therapeutic hypothermia for acute ischemic stroke.

Publications

Still cooling after all these years: Meta-analysis of pre-clinical trials of therapeutic hypothermia for acute ischemic stroke.

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