Rescue therapy for vasospasm following aneurysmal subarachnoid hemorrhage:a propensity score-matched analysis with machine learning

OBJECTIVE Rescue therapies have been recommended for patients with angiographic vasospasm (aVSP) and delayed cerebral ischemia (DCI) following subarachnoid hemorrhage (SAH). However, there is little evidence from randomized clinical trials that these therapies are safe and effective. The primary aim of this study was to apply game theory-based methods in explainable machine learning (ML) and propensity score matching to determine if rescue therapy was associated with better 3-month outcomes following post-SAH aVSP and DCI. The authors also sought to use these explainable ML methods to identify patient populations that were more likely to receive rescue therapy and factors associated with better outcomes after rescue therapy. METHODS Data for patients with aVSP or DCI after SAH were obtained from 8 clinical trials and 1 observational study in the Subarachnoid Hemorrhage International Trialists repository. Gradient boosting ML models were constructed for each patient to predict the probability of receiving rescue therapy and the 3-month Glasgow Outcome Scale (GOS) score. Favorable outcome was defined as a 3-month GOS score of 4 or 5. Shapley Additive Explanation (SNAP) values were calculated for each patient-derived model to quantify feature importance and interaction effects. Variables with high S HAP importance in predicting rescue therapy administration were used in a propensity score-matched analysis of rescue therapy and 3-month GOS scores. RESULTS The authors identified 1532 patients with aVSP or DCI. Predictive, explainable ML models revealed that aneurysm characteristics and neurological complications, but not admission neurological scores, carried the highest relative importance rankings in predicting whether rescue therapy was administered. Younger age and absence of cerebral ischemia/ infarction were invariably linked to better rescue outcomes, whereas the other important predictors of outcome varied by rescue type (interventional or noninterventional). In a propensity score-matched analysis guided by SHAP-based variable selection, rescue therapy was associated with higher odds of 3-month GOS scores of 4-5 (OR 1.63, 95% CI 1.22-2.17). CONCLUSIONS Rescue therapy may increase the odds of good outcome in patients with aVSP or DCI after SAH. Given the strong association between cerebral ischemia/infarction and poor outcome, trials focusing on preventative or therapeutic interventions in these patients may be most able to demonstrate improvements in clinical outcomes. Insights developed from these models may be helpful for improving patient selection and trial design

Development and validation of outcome prediction models for aneurysmal subarachnoid haemorrhage:the SAHIT multinational cohort study

Objective To develop and validate a set of practical prediction tools that reliably estimate the outcome of subarachnoid haemorrhage from ruptured intracranial aneurysms (SAH). Design Cohort study with logistic regression analysis to combine predictors and treatment modality. Setting Subarachnoid Haemorrhage International Trialists' (SAHIT) data repository, including randomised clinical trials, prospective observational studies, and hospital registries. Participants Researchers collaborated to pool datasets of prospective observational studies, hospital registries, and randomised clinical trials of SAH from multiple geographical regions to develop and validate clinical predicti

Neuroinflammation as a Target for Intervention in Subarachnoid Hemorrhage

Aneurysmal subarachnoid hemorrhage (SAH) is a sub-type of hemorrhagic stroke associated with the highest rates of mortality and long-term neurological disabilities. Despite the improvement in the management of SAH patients and the reduction in case fatality in the last decades, disability and mortality remain high in this population. Brain injury can occur immediately and in the first days after SAH. This early brain injury can be due to physical effects on the brain such as increased intracranial pressure, herniations, intracerebral, intraventricular hemorrhage, and hydrocephalus. After the first 3 days, angiographic cerebral vasospasm (ACV) is a common neurological complication that in severe cases can lead to delayed cerebral ischemia and cerebral infarction. Consequently, the prevention and treatment of ACV continue to be a major goal. However, most treatments for ACV are vasodilators since ACV is due to arterial vasoconstriction. Other targets also have included those directed at the underlying biochemical mechanisms of brain injury such as inflammation and either independently or as a consequence, cerebral microthrombosis, cortical spreading ischemia, blood–brain barrier breakdown, and cerebral ischemia. Unfortunately, no pharmacologic treatment directed at these processes has yet shown efficacy in SAH. Enteral nimodipine and the endovascular treatment of the culprit aneurysm, remain the only treatment options supported by evidence from randomized clinical trials to improve patients’ outcome. Currently, there is no intervention directly developed and approved to target neuroinflammation after SAH. The goal of this review is to provide an overview on anti-inflammatory drugs tested after aneurysmal SAH

Análise De Desfecho Clínico Em Pacientes Com Hemorragia Subaracnóide De Alto Grau

Background and Purpose – Poor-grade subarachnoid hemorrhage (SAH) [World Federation of Neurosurgical Societies (WFNS) grade 4 and 5] is associated with high mortality rates and unfavorable functional outcomes. Our aim was to report a single centre cohort of poor-grade SAH patients, combined with a systematic review of studies reporting functional outcome in the poor-grade SAH population. Methods: Data on a cohort of poor-grade SAH patients treated between 2009−2013 was retrospectively collected and combined with a systematic review (from inception to November 2015; PubMed, EMBASE). Two reviewers assessed the studies independently based on predefined inclusion criteria: consecutive poor-grade SAH; functional outcome measured at least 3 months after hemorrhage; and the report of patients who died before aneurysm treatment. Results: A total of 179 patients poor-grade SAH were admitted during the study period. Thirty-three patients (33/179 - 18%) died before, and 25 (25/179 - 14%) after aneurysm treatment, resulting in a total of 58 deaths (58/179 - 32%). One hundred and twenty one patients (121/179 - 68%) were alive at hospital discharge. Sixteen patients (16/179 - 9%) were lost during follow-up. In total, 80 patients (80/179 - 45%) had a favorable functional outcome (mRS ≤ 2). The search yielded 329 publications, 23 met our inclusion criteria with 2,713 subjects enrolled from 1977 to 2014 in 10 countries (including 179 poor-grade patients from our cohort). Mortality rate was 60% (1,683 patients), of which 806 (29%) died before and 877 (31%) died after aneurysm treatment, respectively. Treatment was undertaken in 1,775 patients (1,775/2,826 − 63%): 1,347 by surgical clipping (1,347/1,775 − 76%) and 428 (428/1775 − 24%) by endovascular methods. Outcome was favorable in 794 patients (28%) and unfavorable in 1,867 (66%). When the studies were grouped into decades, favorable outcome increased from 13% in the late 70’s to early 80’s, to 35% in the late 80’s to early 90’s, and remained unchanged thereafter. Conclusion: Although mortality remains high in poor-grade SAH patients, a favorable functional outcome can be achieved in approximately one third of patients. The development of new diagnostic methods and implementation of therapeutic approaches were probably responsible for the decrease in mortality and improvement in the functional outcome from 1970’ to 1990’s. The plateau in functional outcome seen thereafter might be explained by the treatment of sicker and older patients, and by the lack of new therapeutic interventions specific for subarachnoid hemorrhage.Objetivos: A hemorragia subaracnóide (HSA) de alto grau [World Federation of Neurosurgical Societies (WFNS) graus 4 e 5] está associada a altas taxas de mortalidade e desfecho funcionais desfavoráveis. O objetivo deste estudo foi descrever uma coorte de pacientes com HSA de alto grau e realizar uma revisão sistemática de estudos que descreveram desfecho funcional nessa população. Métodos: Coorte retrospectiva de pacientes com HSA de alto grau tratados entre 2009−2013 em centro único em Toronto/Canadá, combinada com uma revisão sistemática da literatura (desde o início até novembro de 2015, PubMed, EMBASE). Dois revisores avaliaram os estudos de forma independente com base em critérios de inclusão pré-definidos: pacientes com HSA de alto grau admitidos consecutivamente; desfecho funcional avaliado pelo menos 3 meses após a hemorragia; e a descrição e inclusão de pacientes que morreram antes do tratamento do aneurisma. Resultados: Um total de 179 pacientes com HSA de alto grau foram admitidos durante o período do estudo. Trinta e três pacientes (33/179 − 18%) morreram antes e 25 (25/179 − 14%) após tratamento do aneurisma, resultando em um total de 58 mortes (58/179 − 32%). Cento e vinte e um pacientes (121/179 − 68%) estavam vivos no momento da alta hospitalar. Dezesseis pacientes (16/179 − 9%) foram perdidos durante o seguimento. No total, 80 pacientes (80/179 − 45%) tiveram um resultado funcional favorável (mRS ≤ 2). A pesquisa bibliográfica obteve 329 publicações, 23 atendendo aos critérios de inclusão, com 2.713 indivíduos incluídos entre 1977 e 2014, em 10 países (incluindo 179 pacientes da nossa coorte). A mortalidade foi de 60% (1.683 pacientes), dos quais 806 (29%) morreram antes, e 877 (31%) morreram após tratamento do aneurisma, respectivamente. O tratamento foi realizado em 1.775 pacientes (1.775/2.826 − 63%): 1.347 tratados com por clipping cirúrgico (1.347/1.775 − 76%) e 428 (428/1775 − 24%) por métodos endovasculares. O desfecho foi favorável em 794 pacientes (28%) e desfavorável em 1.867 (66%). Quando os estudos foram agrupados em décadas, o desfecho favorável aumentou de 13% no final dos anos 70 para início dos anos 80, para 35% no final dos anos 80 e início dos anos 90, e manteve-se inalterado a partir de então. Conclusão: Embora a mortalidade permaneça alta em pacientes com HSA de alto grau, desfecho funcional favorável pode ser alcançado em aproximadamente um terço dos pacientes. O desenvolvimento de novos métodos diagnósticos e a implementação de abordagens terapêuticas foram provavelmente responsáveis pela diminuição da mortalidade e melhora nos resultados funcionais entre 1970 e 1990. O platô observado no desfecho funcional posteriormente pode ser explicado pelo tratamento de pacientes mais garves e mais idosos, e pela ausência de novas intervenções terapêuticas específicas para hemorragia subaracnóidea.Dados abertos - Sucupira - Teses e dissertações (2017

Editorial: Outcomes in subarachnoid hemorrhage

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Use a "gHOST-CAP" in acute brain injury

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