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Background Sex-related differences in patients with aneurysmal subarachnoid hemorrhage (aSAH) exist. More females than males are affected. Aneurysm location is associated to sex. The relationship between sex and outcome, however, is unclear. Possible differences in management might influence the occurrence of primary and secondary brain injury and thus outcome. The study compares demographics, intensity of treatment, complications, and outcome among females and males with aSAH. Methods All consecutive patients with aSAH admitted to the neurocritical care unit, University Hospital Zurich over a 5-year period were eligible in this retrospective study. Patients’ characteristics, comorbidities, aSAH severity, frequency of vasospasm/delayed cerebral ischemia, frequency of invasive interventions, and 3-month outcome were compared by sex. Univariate analysis was performed with the data dichotomized by sex, and outcome. Multivariate analysis for prediction of outcomes was performed. Results Three hundred forty-eight patients were enrolled (64% females). Women were older than men. Comorbidities, scores at admission, and treatment modality were comparable among males and females. Vasospasm and DCI occurred similarly among females and males. Interventions and frequency of intraarterial spasmolysis were comparable between sexes. In the multivariate analysis, increasing age, female sex, increasing comorbidities, WFNS and Fisher grade, and presence of delayed cerebral ischemia were predictors of unfavorable outcome when considering all patients. However, after excluding death as a possible outcome, sex did not remain a predictor of unfavorable outcome. Conclusions In the study population, women with aSAH might have present a worse outcome at 3 months. However, no differences by sex that might explain this difference were found in intensity of treatment and management.

In patients with late-onset Pompe disease (LOPD), the efficacy of the enzyme replacement therapy (ERT) with recombinant human alpha-glucosidase (rhGAA) is difficult to evaluate, due to the clinical heterogeneity and the small sample sizes in published studies. Therefore, we conduct a systematic literature review and meta-analysis of the literature to evaluate the efficacy of ERT in LOPD patients considering the walking distance, respiratory function and muscle strength. Particularly, six-minute walk test (6MWT), forced vital capacity (FVC), medical research council (MRC) grading, quantitative muscle testing (QMT), and quick motor function test (QMFT) were outcomes of interest. Overall, 619 studies were identified in PubMed, EMBASE and by manual search on July 18th, 2020. After an initial assessment, 16 studies were included in the meta-analysis, containing clinical data from 589 patients with LOPD. For the 6MWT, 419 patients were analyzed. Walking distance improved on average, 32.2 m greater during the observed period (p = 0.0003), compared to the distance at the baseline. The meta-analysis did not show any improvement in FVC and only a tendency towards better muscle strength after treatment with ERT, but the difference was not statistically significant. In conclusion, the available data showed that ERT has a significant beneficial efficacy in the improvement of walking distance in LOPD patients and a non-significant improvement of muscle strength. No improvement in respiratory capacity was found. More prospective and controlled trials are needed to demonstrate a clear clinical benefit of ERT.

Purpose: Neurocritical care patients receive prolonged invasive mechanical ventilation (IMV), but there is poor specific information in this high-risk population about the liberation strategies of invasive mechanical ventilation. Methods: ENIO (NCT03400904) is an international, prospective observational study, in 73 intensive care units (ICUs) in 18 countries from 2018 to 2020. Neurocritical care patients with a Glasgow Coma Score (GCS) ≤ 12, receiving IMV ≥ 24h, undergoing extubation attempt or tracheostomy were included. The primary endpoint was extubation failure by day 5. An extubation success prediction score was created, with 2/3 of patients randomly allocated to the training cohort and 1/3 to the validation cohort. Secondary endpoints were the duration of IMV and in-ICU mortality. Results: 1512 patients were included. Among the 1193 (78.9%) patients who underwent an extubation attempt, 231 (19.4%) failures were recorded. The score for successful extubation prediction retained 20 variables as independent predictors. The area under the curve (AUC) in the training cohort was 0.79 95% confidence interval (CI95) [0.71–0.87] and 0.71 CI95 [0.61–0.81] in the validation cohort. Patients with extubation failure displayed a longer IMV duration (14 [7–21] vs 6 [3–11] days) and a higher in-ICU mortality rate (8.7% vs 2.4%). Three hundred and nineteen (21.1%) patients underwent tracheostomy without extubation attempt. Patients with direct tracheostomy displayed a longer duration of IMV and higher in-ICU mortality than patients with an extubation attempt (success and failure). Conclusions: In neurocritical care patients, extubation failure is high and is associated with unfavourable outcomes. A score could predict extubation success in multiple settings. However, it will be mandatory to validate our findings in another prospective independent cohort.

The integration of sex-related differences in neurosurgery is crucial for new, possible sex-specific, therapeutic approaches. In neurosurgical emergencies, such as traumatic brain injury and aneurysmal subarachnoid hemorrhage, these differences have been investigated. So far, little is known concerning the impact of sex on frequency of postoperative complications after elective craniotomy. This study investigates whether sex-related differences exist in frequency of postoperative complications in patients who underwent elective craniotomy for intracranial lesion.All consecutive patients who underwent an elective intracranial procedure over a 2-year period at our center were eligible for inclusion in this retrospective study. Demographic data, comorbidities, frequency of postoperative complications at 24 hours following surgery and at discharge, and hospital length of stay were compared among females and males.Overall, 664 patients were considered for the analysis. Of those, 339 (50.2%) were females. Demographic data were comparable among females and males. More females than males suffered from allergic, muscular, and rheumatic disorders. No differences in frequency of postoperative complications at 24 hours after surgery and at discharge were observed among females and males. Similarly, the hospital length of stay was comparable.In the present study, no sex-related differences in frequency of early postoperative complications and at discharge following elective craniotomy for intracranial lesions were observed.

Background Sex-related differences in patients with spontaneous, non-traumatic intracerebral hemorrhage (ICH) are poorly investigated so far. This study elucidates whether sex-related differences in ICH care in a neurocritical care setting exist, particularly regarding provided care, while also taking patient characteristics, and outcomes into account. Methods This retrospective single center study includes all consecutive patients with spontaneous ICH admitted to the neurocritical care unit in a 10-year period. Patients’ demographics, comorbidities, symptoms at presentation, radiological findings, surgical and medical provided care, intensive care unit mortality and 12 month-mortality, and functional outcome at discharge were compared among men and women. Results Overall, 398 patients were included (male = 198 and female = 200). No differences in demographics, Charlson Comorbidity Index (CCI), symptoms at presentation, radiological findings, intensive care unit mortality and 12-month mortality were observed among men and women. Men received an external ventricular drain (EVD) for hydrocephalus-therapy significantly more often than women, despite similar location of the ICH and radiographic parameters. In the multivariate analysis, EVD insertion was independently associated with male sex (odds ratio 2.82, 95% confidence interval 1.61–4.95, P P = 0.044). Conclusions Sex-related differences in patients with ICH regarding to provided neurosurgical care exist. We provide evidence that insertion of EVD is associated with male sex, disregarding clear reasoning. A sex-bias as well as social factors may play a significant role in decision-making for the insertion of an EVD.

This pilot study assesses the feasibility to detect covert consciousness in clinically unresponsive patients by means of functional near infrared spectroscopy (fNIRS) in a real intensive care unit setting. We aimed to verify if the hemodynamic response to familiar music measured with fNIRS varies according to the level consciousness of the patients.22 neurocritical patients and 6 healthy controls were included. The experiment consisted in 3 subsequent blocks including a first resting state recording, a period of music playback and a second resting state recording. fNIRS measurement were performed on each subject with two optodes on the forehead. Main oscillatory frequencies of oxyhemoglobin signal were analyzed. Spectral changes of low frequency oscillations (LFO) between subsequent experimental blocks were used as a marker of cortical response. Cortical response was compared to the level of consciousness of the patients and their functional outcome, through validated clinical scores.Cortical hemodynamic response to music on the left prefrontal brain was associated with the level of consciousness of the patients and with their clinical outcome after three months.Variations in LFO spectral power measured with fNIRS may be a new marker of cortical responsiveness to detect covert consciousness in neurocritical patients. Left prefrontal cortex may play an important role in the perception of familiar music.We showed the feasibility of a simple fNIRS approach to detect cortical response in the real setting of an intensive care unit.

Background We aimed to evaluate the association between seizures as divided by timing and type (seizures or status epilepticus) and outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). Methods All consecutive patients with aSAH admitted to the neurocritical care unit of the University Hospital Zurich between 2016 and 2020 were included. Seizure type and frequency were extracted from electronic patient files. Results Out of 245 patients, 76 experienced acute symptomatic seizures, with 39 experiencing seizures at onset, 18 experiencing acute seizures, and 19 experiencing acute nonconvulsive status epilepticus (NCSE). Multivariate analysis revealed that acute symptomatic NCSE was an independent predictor of unfavorable outcome (odds ratio 14.20, 95% confidence interval 1.74–116.17, p = 0.013) after correction for age, Hunt-Hess grade, Fisher grade, and delayed cerebral ischemia. Subgroup analysis showed a significant association of all seizures/NCSE with higher Fisher grade (p p = 0.031 for remote symptomatic seizures). However, although acute seizures/NCSE (p = 0.750 and 0.060 for acute seizures/NCSE respectively) were not associated with unfavorable outcome in patients with a high Hunt-Hess grade, they were significantly associated with unfavorable outcome in patients with a low Hunt-Hess grade (p = 0.019 and p Conclusions Acute symptomatic NCSE independently predicts unfavorable outcome after aSAH. Seizures and NCSE are associated with unfavorable outcome, particularly in patients with a low Hunt-Hess grade. We propose that NCSE and the ictal or postictal reduction of Glasgow Coma Scale may hamper close clinical evaluation for signs of delayed cerebral ischemia, and thus possibly leading to delayed diagnosis and therapy thereof in patients with a low Hunt-Hess grade.

Background Venous thromboembolism (VTE) is a recognized complication in patients with traumatic brain injury (TBI) and is associated with increased morbidity and mortality. Currently, no standard exists for optimal timing or a pharmacological agent for VTE prophylaxis (pharmacological thromboprophylaxis - PTP) in patients with TBI. PTP is often delayed out of fear of causing extension of intracranial hemorrhage (ICH). The purpose of this study was to report the frequency of VTE and ICH progression after initiation of PTP with a continuous infusion of unfractionated heparin in patients with moderate to severe TBI, and to identify risk factors associated with development of VTE. Methods In this single-center retrospective study, patients with moderate to severe TBI admitted to the ICU of a Swiss Level I Trauma Center over a three-year period were analyzed. Results In 23 (13%) of the 177 patients included in the study a VTE episode occurred during the hospital stay. ICH progression after initiation of PTP occurred in 7 (4%) patients. In a multivariable logistic regression model, only the timing of initiation of PTP was identified as an independent predictor of VTE. Conclusions In this study population, the risk of developing VTE increased with the delay of initiation of a pharmacological VTE prophylaxis, while ICH progression after initiation of PTP was a rare event.

Background No standards exist regarding decision making for comatose patients, especially concerning life-saving treatments. The aim of this retrospective, single-center study was to analyze outcomes and the decision-making process at the end of life (EOL) in patients with traumatic brain injury (TBI) in a Swiss academic tertiary care hospital. Methods Consecutive admissions to the surgical intensive care unit (ICU) with stays of at least 48 hours between January 1, 2012 and June 30, 2015 in patients with moderate to severe TBI and with fatality within 6 months after trauma were included. Descriptive statistics were used. Results Of 994 ICU admissions with TBI in the study period, 182 had an initial Glasgow Coma Scale 48 hours. For 174 of them, a 6-month outcome assessment based on the Glasgow Outcome Scale (GOS) was available: 43.1% (36.0%-50.5%) had favorable outcomes (GOS 4 or 5), 28.7% (22.5%-35.9%) a severe disability (GOS 3), 0.6% (0%-3.2%) a vegetative state (GOS 2), and 27.6% (21.5%-34.7%) died (GOS 1). Among the GOS 1 individuals, 45 patients had a complete dataset (73% men; median age, 67 years; interquartile range, 43-79 years). Life-prolonging therapies were limited in 95.6% (85.2%-99.2%) of the cases after interdisciplinary prognostication and involvement of the surrogate decision maker (SDM) to respect the patient's documented or presumed will. In 97.7% (87.9%-99.9%) of the cases, a next of kin was the SDM and was involved in the EOL decision and process in 100% (96.3%-100.0%) of the cases. Written advance directives (ADs) were available for 14.0% (6.6%-27.3%) of the patients, and 34.9% (22.4%-49.8%) of the patients had shared their EOL will with relatives before trauma. In the other cases, each patient's presumed will was acknowledged after a meeting with the SDM and was binding for the EOL decision. Conclusions At our institution, the majority of deaths after TBI follow a decision to limit life-prolonging therapies. The frequency of patients in vegetative state 6 months after TBI is lower than expected; this could be due to the high prevalence of limitation of life-prolonging therapies. EOL decision making follows a standardized process, based on patients' will documented in the ADs or on preferences assumed by the SDM. The prevalence of ADs was low and should be encouraged.

Background Hyperventilation-induced hypocapnia (HV) reduces elevated intracranial pressure (ICP), a dangerous and potentially fatal complication of traumatic brain injury (TBI). HV decreases the arteriolar diameter of intracranial vessels, raising the risk of cerebral ischemia. The aim of this study was to characterize the effects of moderate short-term HV in patients with severe TBI by using concomitant monitoring of cerebral metabolism, brain tissue oxygen tension (PbrO2), and cerebral hemodynamics with transcranial color-coded duplex sonography (TCCD). Methods This prospective trial was conducted between May 2014 and May 2017 in the surgical intensive care unit (ICU) at the University Hospital of Zurich. Patients with nonpenetrating TBI older than 18 years of age with a Glasgow Coma Scale (GCS) score

BACKGROUND The purpose of the present study was to analyze clinical features of patients with traumatic brain injury (TBI), their age-related outcomes and determinants of long-term outcome. METHODS This retrospective cohort study was conducted in a level I University Swiss trauma center. Consecutive patients with moderate to severe TBI admitted for more than 48 hours to the Intensive Care Unit (ICU) were included. Patients' and trauma characteristics, management during ICU stay, prognostic scores and long-term outcomes were analyzed. RESULTS Hundred-seventy-four patients (72% males, mean age 49 years) were divided in three age groups: young (≤39 years, N.=69, 39.7%), middle aged (40-64 years, N.=55, 31.6%), and elderly (≥65 years, N.=50, 28.7%). In elderly patients, falls (62%) were the most common cause of TBI. Overall ICU mortality was 15% with no difference among age groups. Within six-months after TBI, 80% of elderly patients presented unfavorable outcomes. Age, pre-existing cardiovascular disease, use of anticoagulants and/or antiplatelet agents, abnormal pupillary reactivity, a high score in Marshall CT classification, and a higher glucose level were associated with unfavorable outcomes in a univariable logistic regression. In a multivariable logistic regression, age and abnormal pupillary reactivity were identified as independent risk factors for unfavorable outcomes, while presence of epidural hematoma and higher hemoglobin levels were predictors for favorable outcomes. CONCLUSIONS Older patients are at higher risk for long-term unfavorable outcomes than younger patients. Use of anticoagulants and/or antiplatelet agents and lower hemoglobin levels during rescue phase are associated with unfavorable long-term outcomes. Fall prevention in the elderly should be a key target of intervention programs.