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Purpose: Uncertainties remain about the safety and efficacy of therapies for managing intracranial hypertension in acute brain injured (ABI) patients. This study aims to describe the therapeutical approaches used in ABI, with/without intracranial pressure (ICP) monitoring, among different pathologies and across different countries, and their association with sixmonths mortality and neurological outcome. Methods: A preplanned subanalysis of the SYNAPSE-ICU study, a multicentre, prospective, international, observational cohort study, describing the ICP treatment, graded according to Therapy Intensity Level (TIL) scale, in patients with ABI during the first week of intensive care unit (ICU) admission. Results: 2320 patients were included in the analysis. The median age was 55 (I-III quartiles = 39-69) years, and 800 (34.5%) were female. During the first week from ICU admission, no-basic TIL was used in 382 (16.5%) patients, mild-moderate in 1643 (70.8%), and extreme in 295 cases (eTIL, 12.7%). Patients who received eTIL were younger (median age 49 (I-III quartiles = 35-62) vs 56 (40-69) years, p

(1) Background: There are limited data regarding the efficacy of convalescent plasma (CP) in critically ill patients admitted to the intensive care unit (ICU) due to coronavirus disease 2019 (COVID-19). We aimed to determine whether CP is associated with better clinical outcome among these patients. (2) Methods:&nbsp, A&nbsp, retrospective single-center study including adult patients with laboratory-confirmed SARS-CoV-2 infection admitted to the ICU for acute respiratory failure. The primary outcome was time to clinical improvement, within 28 days, defined as patient discharged alive or reduction of 2 points on a 6-point disease severity scale. (3)&nbsp, Results:&nbsp, Overall, 110 COVID-19 patients were admitted. Thirty-two patients (29%) received CP, among them, 62.5% received at least one CP with high neutralizing antibody titers (≥1:160). Clinical improvement occurred within 28 days in 14 patients (43.7%) of the CP group vs. 48 patients (61.5%) in the non-CP group (hazard ratio (HR): 0.75 (95% CI: 0.41–1.37), p = 0.35). After adjusting for potential confounding factors, CP was not independently associated with time to clinical improvement (HR: 0.53 (95% CI: 0.23–1.22), p = 0.14). Additionally, the average treatment effects of CP, calculated using the inverse probability weights (IPW), was not associated with the primary outcome (−0.14 days (95% CI: −3.19–2.91 days), p = 0.93). Hospital mortality did not differ between CP and non-CP groups (31.2% vs. 19.2%, p = 0.17, respectively). Comparing CP with high neutralizing antibody titers to the other group yielded the same findings. (4) Conclusions: In this study of life-threatening COVID-19 patients, CP was not associated with time to clinical improvement within 28 days, or hospital mortality.

Objectives: There are limited data regarding the efficacy of methylprednisolone in patients with acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) requiring invasive mechanical ventilation. We aimed to determine whether methylprednisolone is associated with increases in the number of ventilator-free days (VFDs) among these patients. Design: Retrospective single-center study. Setting: Intensive care unit. Patients: All patients with ARDS due to confirmed SARS-CoV-2 infection and requiring invasive mechanical ventilation between 1 March and 29 May 2020 were included. Interventions: None. Measurements and Main Results: The primary outcome was ventilator-free days (VFDs) for the first 28 days. Defined as being alive and free from mechanical ventilation. The primary outcome was analyzed with competing-risks regression based on Fine and Gray’s proportional sub hazards model. Death before day 28 was considered to be the competing event. A total of 77 patients met the inclusion criteria. Thirty-two patients (41.6%) received methylprednisolone. The median dose was 1 mg·kg−1 (IQR: 1–1.3 mg·kg−1) and median duration for 5 days (IQR: 5–7 days). Patients who received methylprednisolone had a mean 18.8 VFDs (95% CI, 16.6–20.9) during the first 28 days vs. 14.2 VFDs (95% CI, 12.6–16.7) in patients who did not receive methylprednisolone (difference, 4.61, 95% CI, 1.10–8.12, p = 0.001). In the multivariable competing-risks regression analysis and after adjusting for potential confounders (ventilator settings, prone position, organ failure support, severity of the disease, tocilizumab, and inflammatory markers), methylprednisolone was independently associated with a higher number of VFDs (subhazards ratio: 0.10, 95% CI: 0.02–0.45, p = 0.003). Hospital mortality did not differ between the two groups (31.2% vs. 28.9%, p = 0.82). Hospital length of stay was significantly shorter in the methylprednisolone group (24 days [IQR: 15–41 days] vs. 37 days [IQR: 23–52 days], p = 0.046). The incidence of positive blood cultures was higher in patients who received methylprednisolone (37.5% vs. 17.8%, p = 0.052). However, 81% of patients who received methylprednisolone also received tocilizumab. The number of days with hyperglycemia was similar in the two groups. Conclusions: Methylprednisolone was independently associated with increased VFDs and shortened hospital length of stay. The combination of methylprednisolone and tocilizumab was associated with a higher rate of positive blood cultures. Further trials are needed to evaluate the benefits and safety of methylprednisolone in moderate or severe COVID-19 ARDS.

Objectives: There are limited data regarding the efficacy of methylprednisolone in patients with acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) requiring invasive mechanical ventilation. We aimed to determine whether methylprednisolone increases the number of ventilator-free days (VFDs) among these patients. Design: Retrospective single-center study Setting: Intensive care unit Patients: All patients with ARDS due to confirmed SARS-CoV-2 infection and requiring invasive mechanical ventilation between 1 March and 29 May 2020 were included Interventions: None Measurements and Main Results: The primary outcome was ventilator-free days (VFDs) during the first 28 days, defined as being alive and free from mechanical ventilation. The primary outcome was analyzed with competing-risks regression based on Fine and Gray’s proportional subhazards model. Death before day 28 was considered to be the competing event. A total of 77 patients met the inclusion criteria. Thirty-two patients (41.6%) received methylprednisolone. The median dose was 1 mg.kg-1 (IQR: 1-1.3 mg.kg-1) and median duration of 5 days (IQR:5-7 days). Patients who received methylprednisolone had a mean 18.8 VFDs (95% CI, 16.6-20.9) during the first 28 days vs. 14.2 VFDs (95% CI, 12.6-16.7) in patients who did not receive methylprednisolone (difference, 4.61; 95% CI, 1.10-8.12; P = 0.001). In the multivariable competing-risks regression analysis and after adjusting for potential confounders (ventilator settings, prone position, organ failure support, severity of the disease, tocilizumab, and inflammatory markers), methylprednisolone was independently associated with a higher number of VFDs (subhazards ratio: 0.10, 95%CI: 0.02-0.45; p=0.003). Hospital mortality did not differ between the two groups (31.2% vs. 28.9%, p=0.82). Hospital length of stay was significantly shorter in the methylprednisolone group (24 days [IQR:15-41 days] vs. 37 days [IQR:23-52 days], p=0.046). The incidence of positive blood cultures was higher in patients who received methylprednisolone (37.5% vs. 17.8%, p=0.052). However, 91% of patients who received methylprednisolone also received tocilizumab. The number of days with hyperglycemia was similar in the two groups. Conclusions: Methylprednisolone was independently associated with increased VFDs and shortened hospital length of stay. The combination of methylprednisolone and tocilizumab was associated with a higher rate of positive blood cultures. Further trials are needed to evaluate the benefits and safety of methylprednisolone in moderate or severe COVID-19 ARDS.

Highlights • When comparing stroke admissions from March 1st-May 10th in 2019 and 2020 at a single comprehensive stroke center in Middle East, there was a 41.9% increase in stroke admissions in 2020. A higher rate of large vessel occlusion (LVO) and significant delay in initiation of mechanical thrombectomy after hospital arrival was observed in 2020. • Among all COVID-19 admissions in 2020, 5.24% patients suffered stroke including 3.21% with ischemic and 2% with hemorrhagic stroke. • Patients with COVID-19 and ischemic stroke were significantly younger, predominantly male, had fewer vascular risk factors, had more severe clinical presentation, and higher rate of LVO ccompared to ischemic stroke patients without COVID-19 • For hemorrhagic stroke, COVID-19 patients did not differ from non-COVID-19 patients., Objective: To compare ischemic and hemorrhagic stroke patients with COVID-19 to non-COVID-19 controls, and to describe changes in stroke admission patterns during the pandemic. Methods:This is a single center, retrospective, observational study. All consecutive patients admitted with primary diagnosis of ischemic/ hemorrhagic stroke between March1st -May10th 2020 were included and compared with the same time period in 2019. Results: There was a 41.9% increase in stroke admissions in 2020 (148 vs 210,P = .001). When comparing all ischemic strokes, higher rate of large vessel occlusion (LVO) (18.3% vs 33.8%,P = .008) and significant delay in initiation of mechanical thrombectomy after hospital arrival (67.75 vs 104.30 minutes,P = .001) was observed in 2020. When comparing all hemorrhagic strokes, there were no differences between the two years. Among 591 COVID-19 admissions, 31 (5.24%) patients with stroke including 19 with ischemic (3.21%) and 12 with hemorrhagic stroke (2.03%) were identified. Patients with COVID-19 and ischemic stroke were significantly younger (58.74 vs 48.11 years,P = .002), predominantly male (68.18% vs 94.74%,P = .016), had lesser vascular risk factors, had more severe clinical presentation (NIHSS 7.01 vs 17.05,P

The mechanisms and phenotype of ischemic stroke associated with coronavirus disease 2019 (COVID-19) remain uncertain. A retrospective study was conducted in patients with COVID-19 presenting with ischemic stroke from March 1 to May 25, 2020, and cases with large-vessel occlusion were identified. To provide baseline institutional stroke data within and outside the COVID-19 pandemic, all consecutive ischemic stroke and TIA admissions (COVID and non-COVID) to the hospital during a 10-week period from March 1 to May 10, 2020, were collected and compared with data from the same time period in 2019. Among 20 patients with COVID-19 and acute ischemic stroke, 15 (75%) had large-vessel occlusion. These patients were young (mean age, 46.5 years), male (93%), without major burden of traditional cardiovascular risk factors, and had a severe stroke presentation. Large-vessel occlusions were observed in multiple vessels (40%), uncommonly affected vessels, and atypical locations with a large thrombus burden. Systemic thrombosis separate from large-vessel occlusion was not uncommon (26%). At short-term follow-up, stroke etiology remained undetermined in 46% of patients and functional outcome was poor. The above findings raise the possibility of stroke related to mechanisms induced by the COVID-19 infection itself, including a hypercoagulable state and/or endothelial damage. In addition, they document the severe presentation and poor outcomes of large-vessel occlusion in COVID-19 ischemic stroke.

Activated prothrombin complex concentrates factor eight inhibitor bypassing activity (FEIBA) has been recommended for reversing novel oral anticoagulants (NOAC) in the context of intracerebral hemorrhage (ICH), though few clinical studies report its use.A prospective study of patients with spontaneous ICH was conducted from May 2013 to May 2015. Hospital complications including hemorrhage (gastrointestinal bleeding, anemia requiring transfusion, and surgical site bleeding) and thrombosis (pulmonary embolus, deep vein thrombosis, ischemic stroke, and myocardial infarction) were recorded. All ICH patients underwent baseline head CT and a follow-up stability scan in 6 h. NOAC taken within 48 h of presentation was reversed with FEIBA (50 u/kg) per protocol. Three-month outcomes were assessed using the modified rankin score (mRS).Of 127 ICH patients enrolled, 6 (5 %) had NOAC-related ICH including: oral factor XA inhibitor N = 5 (4 %; N = 4 rivaroxaban, N = 1 apixaban] and direct thrombin inhibitor N = 1 (0.8 %; dabigatran). The indication for NOAC was atrial fibrillation in all patients and the median CHADS2-VASC score was 4 (range 2-5). The median admission NIHSS was 2 (range 0-14) and the median ICH volume was 8 mL (range 1-20). Five patients (3 rivaroxaban, 1 apixaban, 1 dabigatran) presented within 48 h and received FEIBA within a median of 13 h (range 10-29 h) from their last NOAC dose and 8 h (range 4.5-20) from the time last known well. None of the patients had ICH expansion, hemorrhagic, or thrombotic complications. Three-month median mRS was 1 (range 0-6).In this small case series, reversal of NOAC with FEIBA was not associated with ICH expansion or any thrombotic or hemorrhagic complications.

Background Nosocomial infections are frequent complications in patients with intracerebral hemorrhage. Objectives To determine the prevalence, risk factors, and outcomes of nosocomial infections in patients with intracerebral hemorrhage. Methods Prospectively collected data on patients with spontaneous intracerebral hemorrhage between January 2009 and June 2012 were retrospectively reviewed. Patients who had nosocomial infection during the hospital stay were compared with patients who did not. Poor outcome was defined as death or discharge to a long-term nursing facility. Results At least 1 nosocomial infection developed in 26% of 202 patients with intracerebral hemorrhage. The most common infections were pneumonia (18%), urinary tract infection (12%), meningitis or ventriculitis (3%), and bacteremia (1%). On univariate analysis, independent predictors of nosocomial infection were intraventricular hemorrhage, hydrocephalus, low score on the Glasgow Coma Scale at admission, hyperglycemia at admission, and treatment with mechanical ventilation. On multivariate regression analysis, the only significant predictor of nosocomial infection was intraventricular hemorrhage (odds ratio, 5.4; 95% CI, 1.2–11.4; P = .02). Patients with nosocomial infection were more likely than those without to require a percutaneous gastrostomy tube (odds ratio, 33.1, 95% CI, 23.3–604.4; P < .001) and to have a longer stay in the intensive care unit or hospital without a significant increase in mortality. Patients with nosocomial pneumonia were also more likely to have a poor outcome (P < .001). Conclusion Pneumonia was the most common infection among patients with intracerebral hemorrhage.

Subarachnoid hemorrhage is a cerebrovascular emergency that has potential for a prolonged and complicated hospital course, carrying high rates of morbidity and mortality. The most common cause of spontaneous subarachnoid hemorrhage is aneurysm rupture. Most patients with aneurysmal subarachnoid hemorrhage will need to be monitored closely in an intensive care unit after treatment of the ruptured aneurysm to monitor and prevent potential neurological and medical complications. Neurological complications include seizures, hydrocephalus, high intracranial pressure, cerebral vasospasm, and delayed cerebral ischemia, all of which can worsen outcome of postsubarachnoid hemorrhage. Medical complications that can occur in these patients include hyponatremia, which is commonly caused by either cerebral salt wasting syndrome or syndrome of inappropriate antidiuretic hormone secretion. Close monitoring of the extracellular fluid status and accurately diagnosing the etiology of hyponatremia is important in order to provide the appropriate management and avoid its potential sequelae such as hypovolemia, cerebral edema, and secondary symptomatic cerebral vasospasm.

ImportanceTreatments for symptomatic intracerebral hemorrhage (sICH) are based on expert opinion, with limited data available on efficacy.ObjectiveTo better understand the natural history of thrombolysis-related sICH, with a focus on the efficacy of various treatments used.Design, setting, and participantsMulticenter retrospective study between January 1, 2009, and April 30, 2014, at 10 primary and comprehensive stroke centers across the United States. Participants were all patients with sICH, using the definition by the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST), which included a parenchymal hematoma type 2 and at least a 4-point increase in the National Institutes of Health Stroke Scale score.Main outcomes and measuresThe primary outcome was in-hospital mortality, and the secondary outcome was hematoma expansion, defined as a 33% increase in the hematoma volume on follow-up imaging.ResultsOf 3894 patients treated with intravenous recombinant tissue plasminogen activator (rtPA) within 4½ hours after symptom onset of ischemic stroke, 128 (3.3%) had sICH. The median time from initiation of rtPA therapy to sICH diagnosis was 470 minutes (range, 30-2572 minutes), and the median time from diagnosis to treatment of sICH was 112 minutes (range, 12-628 minutes). The in-hospital mortality rate was 52.3% (67 of 128), and 26.8% (22 of 82) had hematoma expansion. In the multivariable models, code status change to comfort measures after sICH diagnosis was the sole factor associated with increased in-hospital mortality (odds ratio, 3.6; 95% CI, 1.2-10.6). Severe hypofibrinogenemia (fibrinogen level

Background: The most feared complication from thrombolysis is symptomatic intracerebral hemorrhage (sICH). Current treatments for sICH are based on limited data. We aim to the efficacy of treatments utilized. Methods: We conducted a collaborative study from 5 academic stroke centers (Columbia University, Massachusetts General Hospital, University of Arkansas, Washington University, and UCLA) on acute post-thrombolysis sICH treatment. The definition of sICH was based on the Safe Implementation of Thrombolysis in Stroke criteria. The primary outcome was in-hospital mortality. Analysis was performed using Fisher’s test and independent t-test, followed by multivariable regression; p Results: We identified 87 patients with sICH from 1/09 to 4/14. Mean time from rtPA infusion to sICH diagnosis was 12±10 hours and mean time to treatment after diagnosis 2.5 ± 2.3 hours. 91% were diagnosed more than 2 hours from initiation of rtPA. The median NIHSS was lower in patients diagnosed in the first 3 hours versus after 3 hours (10 vs. 18, p=0.01). We found no association between receiving any treatment versus none with in-hospital mortality (37% vs 52%, p = 0.1). Factors associated with higher mortality were code status change within 24 hours (56% vs. 13%, p Conclusion: The treatment of post-thrombolysis sICH did not reduce mortality. Possible explanations include perception of futility, prolonged time to diagnosis, and endovascular treatment. More aggressive neurological monitoring beyond two hours from rtPA and screening high risk patients, especially those with high NIHSS score may potentially reduce time to diagnosis/treatment. Innovative treatment with high efficacy and short onset of action should be studied to improve the outcome of sICH.

Hematoma growth is an independent determinant of outcome in patients with intracerebral hemorrhage (ICH). Predictors of hematoma expansion are poorly defined. Our aim is to determine predictors of hematoma expansion in patients with ICH.We reviewed our prospective database of patients with ICH between January 2009 and June 2012. Patients were divided into two groups based on the presence or absence of hematoma expansion. Hematoma volume was calculated by thin volumetric cuts using special software. Expansion was defined as 33% increase in hematoma volume over 24 hours. We compared risk factors, laboratory parameters, medications and CT findings between the two groups using Fisher's exact test. A multivariate regression analysis was performed to identify predictors of expansion.We identified 200 patients with ICH. On univariate analysis, patients with hematoma expansion were more likely to have Warfarin use (37% vs. 11% p = 0.001), low admission GCS (9 ± 4, 11 ± 4, p = 0.003), intraventricular hemorrhage (IVH) (79% vs. 45% p = 0.002) and hydrocephalus (43% vs. 22% p = 0.032). On multivariate regression analysis, prior Warfarin use (OR = 3.6, 95% CI: 1.3,10.3; p = 0.016) and IVH (OR = 5.7, 95% CI: 1.5,20.9; p = 0.009) were significant predictors of hematoma expansion. The ICU length of stay (8 ± 8 vs. 4 ± 6, p = 0.004), intubation rate (82% vs. 32%, p = 0.034), and hospital mortality (68% vs. 20%, p =0.001) were significantly higher among patients with hematoma expansion.Patient with prior Warfarin use and IVHs are at risk of hematoma expansion. Aggressive measures to prevent hematoma growth are important in these patients.