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Ischemic strokes are frequent neurological diseases. Annual incidence in Europe varies from 100 to 350/100.000 inhabitants per year. Strokes are leading cause of long-term invalidity and 3rd cause of death worldwide. Reperfusion therapy represents therapeutic keystone. In the year 2015, positive results of five randomized studies showed the superiority and efficacy of mechanical thrombectomy compared to standard treatment in acute ischemic stroke due to large vessel occlusion. Positive results of DAWN and DEFUSE-3 trials published in 2017/2018 showed benefit for endovascular therapy beyond standard therapeutic time window in strictly selected patients based on imaging of ischemic penumbra using CT perfusion or MRI. Thus, "tissue" window is becoming a limiting factor for mechanical thrombectomy now instead of previous "time" window. Use of aspiration thrombectomy and choice of suitable anesthesia caused increase of procedural efectivity of intervention. There are 3 possible positive outcome predictors which can be influenced in acute care. Blood pressure seems to be the key variable in acute phase. Lowering the values is associated with better outcome up to systolic blood pressure under 100 torr where growth of complications is observed. Oxygen stress protective effect of normoglycaemia appears to be more important in case of mechanical thrombectomy. Body temperature seems to be good predictor of outcome in relation to other characteristics of the patient. Its' sole decrease via therapeutic hypothermia is in the cases of acute ischaemic stroke associated with significantly higher incidence of severe complications. [ABSTRACT FROM AUTHOR]

Background: The application of therapeutic hypothermia (TH) for 12 to 24 hours following out-of-hospital cardiac arrest (OHCA) has been associated with decreased mortality and improved neurological function. However, the optimal duration of cooling is not known. We aimed to investigate whether targeted temperature management (TTM) at 33 ± 1 °C for 48 hours compared to 24 hours results in a better long-term neurological outcome.Methods: The TTH48 trial is an investigator-initiated pragmatic international trial in which patients resuscitated from OHCA are randomised to TTM at 33 ± 1 °C for either 24 or 48 hours. Inclusion criteria are: age older than 17 and below 80 years; presumed cardiac origin of arrest; and Glasgow Coma Score (GCS) <8, on admission. The primary outcome is neurological outcome at 6 months using the Cerebral Performance Category score (CPC) by an assessor blinded to treatment allocation and dichotomised to good (CPC 1-2) or poor (CPC 3-5) outcome. Secondary outcomes are: 6-month mortality, incidence of infection, bleeding and organ failure and CPC at hospital discharge, at day 28 and at day 90 following OHCA. Assuming that 50 % of the patients treated for 24 hours will have a poor outcome at 6 months, a study including 350 patients (175/arm) will have 80 % power (with a significance level of 5 %) to detect an absolute 15 % difference in primary outcome between treatment groups. A safety interim analysis was performed after the inclusion of 175 patients.Discussion: This is the first randomised trial to investigate the effect of the duration of TTM at 33 ± 1 °C in adult OHCA patients. We anticipate that the results of this trial will add significant knowledge regarding the management of cooling procedures in OHCA patients.Trial Registration: NCT01689077. [ABSTRACT FROM AUTHOR]

Aim: Comparing the outcome after out-of-hospital cardiac arrest (OHCA) in men and women and to determine whether sex modifies the effect of targeted temperature management (TTM) at 33 or 36°C.Methods: The TTM trial randomized 950 patients to TTM at 33 or 36°C for 24h. This predefined sub-study of the TTM trial assessed survival and neurological outcome defined as Cerebral Performance Category (CPC) and modified Rankin Scale (mRS) using female sex as main predictor of outcome, in relation to level of TTM and other confounding factors.Results: Compared to men, women more often had OHCA at home, p=0.04 and less often had bystander defibrillation, p=0.01. No other differences in arrest circumstances were found. Coronary angiography (CAG) and percutaneous coronary intervention (PCI) <24h after ROSC was less often performed in women, both: p=0.02. Female sex was associated with higher mortality in univariate analysis, hazard ratio (HR)=1.29, CI=1.04-1.61, p=0.02 compared to men. Adjusting for demographic factors (age and comorbidity), arrest circumstances, pre-hospital findings, inclusion sites, treatments and status at admission reduced this: HR=1.11, CI=0. 87-1.41, p=0.42, and sex was no longer an independent risk factor for death. The effect of sex did not modify the effect of TTM at 33 and 36°C, pinteraction=0.73.Conclusion: Female sex seems associated with adverse outcome, but this association is largely explained by differences in arrest circumstances and in-hospital treatment. Our data shows no interaction between sex and the effect of targeting 33 vs. 36°C. [ABSTRACT FROM AUTHOR]

Abstract: Background: Therapeutic hypothermia (TH) following perinatal asphyxial encephalopathy in term infants improves mortality and neurodevelopmental outcome. In Europe, most neonatal units perform active cooling whereas in Switzerland passive cooling is predominantly used. Aims: (i) To determine how many infants were cooled within the last 5years in Switzerland, (ii) to assess the cooling methods, (iii) to evaluate the variation of temperature of different cooling methods, and (iv) to evaluate the use of neuromonitoring. Study design: Retrospective cohort study. Patients: Notes of all cooled term infants between March 2005 and December 2010 in 9 perinatal and two paediatric intensive care centres were retrospectively reviewed. Active cooling was compared to passive cooling alone and to passive cooling in combination with gel packs. Results: 150 infants were cooled. Twenty-seven (18.2%) were cooled actively, 34 (23%) passively and 87 (58.8%) passively in combination with gel packs. Variation of temperature was significantly different between the three methods. Passive cooling had a significant higher variation of temperature (SD of 0.89) than both passive cooling in combination with gel packs (SD of 0.79) and active cooling (SD of 0.76). aEEG before TH was obtained in 35.8% of the infants and 86.5% had full EEG. One cUS was performed in 95.3% and MRI in 62.2% of the infants. Conclusion: Target temperature can be achieved with all three cooling methods. Passive cooling has the highest variation of temperature. Neuromonitoring should be improved in Swiss neonatal and paediatric intensive care units. Our results stress the importance of national registries. [Copyright &y& Elsevier]

Therapeutic hypothermia allows us to improve both survival and neurological recovery in patients with different causes of neuronal aggression. This article is based on demographic studies conducted both in the U.S. and Europe, and aims to present the pathophysiological mechanisms of these therapeutic methods and their indications, focusing on patients who suffered cardiac arrest. There are also presented criteria for including and excluding patients in the studies, methods of inducing hypothermia, and treatment protocols. Variables related to the timing of the start method of cooling, process cooling, rate, depth, duration of cooling and reheating are disputed here, which may all have an impact on mortality and morbidity. However, at this time, these variables are not well studied and are at present in several experimental and clinical studies. In addition, these variables are most likely to have different levels of importance depending on clinical indications. [ABSTRACT FROM AUTHOR]

Background: Perinatal asphyxia and resulting hypoxic-ischemic encephalopathy is a major cause of death and long-term disability in term born neonates. Up to 20,000 infants each year are affected by HIE in Europe and even more in regions with lower level of perinatal care. The only established therapy to improve outcome in these infants is therapeutic hypothermia. Allopurinol is a xanthine oxidase inhibitor that reduces the production of oxygen radicals as superoxide, which contributes to secondary energy failure and apoptosis in neurons and glial cells after reperfusion of hypoxic brain tissue and may further improve outcome if administered in addition to therapeutic hypothermia.Methods: This study on the effects of ALlopurinol in addition to hypothermia treatment for hypoxic-ischemic Brain Injury on Neurocognitive Outcome (ALBINO), is a European double-blinded randomized placebo-controlled parallel group multicenter trial (Phase III) to evaluate the effect of postnatal allopurinol administered in addition to standard of care (including therapeutic hypothermia if indicated) on the incidence of death and severe neurodevelopmental impairment at 24 months of age in newborns with perinatal hypoxic-ischemic insult and signs of potentially evolving encephalopathy. Allopurinol or placebo will be given in addition to therapeutic hypothermia (where indicated) to infants with a gestational age ≥ 36 weeks and a birth weight ≥ 2500 g, with severe perinatal asphyxia and potentially evolving encephalopathy. The primary endpoint of this study will be death or severe neurodevelopmental impairment versus survival without severe neurodevelopmental impairment at the age of two years. Effects on brain injury by magnetic resonance imaging and cerebral ultrasound, electric brain activity, concentrations of peroxidation products and S100B, will also be studied along with effects on heart function and pharmacokinetics of allopurinol after iv-infusion.Discussion: This trial will provide data to assess the efficacy and safety of early postnatal allopurinol in term infants with evolving hypoxic-ischemic encephalopathy. If proven efficacious and safe, allopurinol could become part of a neuroprotective pharmacological treatment strategy in addition to therapeutic hypothermia in children with perinatal asphyxia.Trial Registration: NCT03162653, www.ClinicalTrials.gov , May 22, 2017. [ABSTRACT FROM AUTHOR]

Approximately 400,000 Europeans are yearly resuscitated from out-of-hospital cardiac arrest (OHCA).(1,2) Despite evolving evidence based guidelines for cardiopulmonary resuscitation (CPR), survival rates after OHCA has not improved much in several places around the world. However, a potential for improved survival is absolutely present, based on the huge spread in worldwide survival; some cities with survival over 20-30% and some cities with just a few percent.(1,2) These survival differences can partly be explained by different definitions of OHCA,(2) but mainly due to the overall quality of the local Chain of Survival (COS)(3); early arrest recognition and call for help, early CPR, early defibrillation and early post resuscitation care. By identifying and thereafter improving weak links in the local COS, survival can indeed increase. This review will focus on the quality of the last link in the COS, the hospital treatment after return of spontaneuous circulation (ROSC), and how good quality post resuscitation care can improve not only survival, but survival with neurologically intact outcome., (Copyright © 2013 Elsevier Ltd. All rights reserved.)