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Uncertainty persists over the effects of blood pressure lowering in acute intracerebral haemorrhage. We aimed to combine individual patient-level data from the two largest randomised controlled trials of blood pressure lowering strategies in patients with acute intracerebral haemorrhage to determine the strength of associations between key measures of systolic blood pressure control and safety and efficacy outcomes. We did a preplanned pooled analysis of individual patient-level data acquired from the main phase of the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT2) and the second Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH-II) trial. These trials included adult patients aged 19–99 years with spontaneous (non-traumatic) intracerebral haemorrhage and elevated systolic blood pressure, without a clear indication or contraindication to treatment. Patients were excluded if they had a structural cerebral cause for the intracerebral haemorrhage, had a low score (3–5) on the Glasgow Coma Scale, or required immediate neurosurgery. Our primary analysis assessed the independent associations between three post-randomisation systolic blood pressure summary measures—magnitude of reduction in 1 h, mean achieved systolic blood pressure, and variability in systolic blood pressure between 1 h and 24 h—and the primary outcome of functional status, as defined by the distribution of scores on the modified Rankin Scale at 90 days post-randomisation. We analysed the systolic blood pressure measures as continuous variables using generalised linear mixed models, adjusted for baseline covariables and trial. The primary and safety analyses were done in a modified intention-to-treat population, which only included patients with sufficient data on systolic blood pressure. 3829 patients (mean age 63·1 years [SD 12·9], 1429 [37%] women, and 2490 [65%] Asian ethnicity) were randomly assigned in INTERACT2 and ATACH-II, with a median neurological impairment defined by scores on the National Institutes of Health Stroke Scale of 11 (IQR 6–16) and median time from the onset of symptoms of intracerebral haemorrhage to randomisation of 3·6 h (2·7–4·4). We excluded 20 patients with insufficient or no systolic blood pressure data, and we imputed missing systolic blood pressure data in 23 (1%) of the remaining 3809 patients. Overall, the mean magnitude of early systolic blood pressure reduction was 29 mm Hg (SD 22), and subsequent mean systolic blood pressure achieved was 147 mm Hg (15) and variability in systolic blood pressure was 14 mm Hg (8). Achieved systolic blood pressure was continuously associated with functional status (improvement per 10 mm Hg increase adjusted odds ratio [OR] 0·90 [95% CI 0·87–0·94], p<0·0001). Symptomatic hypotension occurred in 28 (1%) patients, renal serious adverse events occurred in 26 (1%) patients, and cardiac serious adverse events occurred in 99 (3%) patients. Our pooled analyses indicate that achieving early and stable systolic blood pressure seems to be safe and associated with favourable outcomes in patients with acute intracerebral haemorrhage of predominantly mild-to-moderate severity. None.

Abstract BACKGROUND Minimally invasive surgery procedures, including stereotactic catheter aspiration and clearance of intracerebral hemorrhage (ICH) with recombinant tissue plasminogen activator hold a promise to improve outcome of supratentorial brain hemorrhage, a morbid and disabling type of stroke. A recently completed Phase III randomized trial showed improved mortality but was neutral on the primary outcome (modified Rankin scale score 0 to 3 at 1 yr). OBJECTIVE To assess surgical performance and its impact on the extent of ICH evacuation and functional outcomes. METHODS Univariate and multivariate models were used to assess the extent of hematoma evacuation efficacy in relation to mRS 0 to 3 outcome and postulated factors related to patient, disease, and protocol adherence in the surgical arm (n = 242) of the MISTIE trial. RESULTS Greater ICH reduction has a higher likelihood of achieving mRS of 0 to 3 with a minimum evacuation threshold of ≤15 mL end of treatment ICH volume or ≥70% volume reduction when controlling for disease severity factors. Mortality benefit was achieved at ≤30 mL end of treatment ICH volume, or >53% volume reduction. Initial hematoma volume, history of hypertension, irregular-shaped hematoma, number of alteplase doses given, surgical protocol deviations, and catheter manipulation problems were significant factors in failing to achieve ≤15 mL goal evacuation. Greater surgeon/site experiences were associated with avoiding poor hematoma evacuation. CONCLUSION This is the first surgical trial reporting thresholds for reduction of ICH volume correlating with improved mortality and functional outcomes. To realize the benefit of surgery, protocol objectives, surgeon education, technical enhancements, and case selection should be focused on this goal.

In this randomized trial involving patients with acute stroke, prehospital administration of magnesium sulfate by paramedics within 2 hours after the onset of stroke symptoms (within 1 hour for 74% of patients) did not improve neurologic outcomes. Stroke is the second leading cause of death and a leading cause of adult disability worldwide. Unfortunately, currently available therapies for acute ischemic stroke, which are all reperfusion-based, are only moderately effective. 1 , 2 Treatment with tissue plasminogen activator (t-PA), the only pharmacologic treatment approved by a regulatory agency for the treatment of acute ischemic stroke, results in early reperfusion in less than half of treated patients, can be started only after neuroimaging has ruled out intracerebral hemorrhage, and is used in only 2 to 7% of patients with acute ischemic stroke in the United States. 1 Mechanical thrombectomy devices improve patient . . .

Purpose We develop a new risk score to predict patients with stroke-associated pneumonia (SAP) who have an acute intracranial hemorrhage (ICH). Method We applied logistic regression to develop a new risk score called ICH-LR2S2. It was derived from examining a dataset of 70,540 ICH patients between 2015 and 2018 from the Chinese Stroke Center Alliance (CSCA). During the training of ICH-LR2S2, patients were randomly divided into two groups – 80% for the training set and 20% for model validation. A prospective test set was developed using 12,523 patients recruited in 2019. To further verify its effectiveness, we tested ICH-LR2S2 on an external dataset of 24,860 patients from the China National Stroke Registration Management System II (CNSR II). The performance of ICH-LR2S2 was measured by the area under the receiver operating characteristic curve (AUROC). Results The incidence of SAP in the dataset was 25.52%. A 24-point ICH-LR2S2 was developed from independent predictors, including age, modified Rankin Scale, fasting blood glucose, National Institutes of Health Stroke Scale admission score, Glasgow Coma Scale score, C-reactive protein, dysphagia, Chronic Obstructive Pulmonary Disease, and current smoking. The results showed that ICH-LR2S2 achieved an AUC = 0.749 [95% CI 0.739–0.759], which outperforms the best baseline ICH-APS (AUC = 0.704) [95% CI 0.694–0.714]. Compared with the previous ICH risk scores, ICH-LR2S2 incorporates fasting blood glucose and C-reactive protein, improving its discriminative ability. Machine learning methods such as XGboost (AUC = 0.772) [95% CI 0.762–0.782] can further improve our prediction performance. It also performed well when further validated by the external independent cohort of patients (n = 24,860), ICH-LR2S2 AUC = 0.784 [95% CI 0.774–0.794]. Conclusion ICH-LR2S2 accurately distinguishes SAP patients based on easily available clinical features. It can help identify high-risk patients in the early stages of diseases.

Background The aim of this study is to investigate the association between intravenous tirofiban and symptomatic intracranial hemorrhage (SICH) in patients with acute ischemic stroke (AIS) secondary to large vessel occlusion (LVO) receiving endovascular thrombectomy (EVT) within 24 h of time last known well (LKW). Methods Patients with AIS-LVO who were randomly assigned to receive intravenous tirofiban or placebo before EVT within 24 h of time LKW and had follow-up brain non-contrast computed tomography within 24 h after stopping tirofiban treatment were derived from “RESCUE BT”: a multicenter, randomized, placebo-controlled, double-blind trial. All eligible patients were divided into SICH and NO-SICH groups. Subgroup analyses were performed to explore for heterogeneity. Results Of 945 patients included in this cohort, there were 76 (8.0%) in the SICH group and 869 (92.0%) in the NO-SICH group. The incidence of SICH was not higher in patients receiving intravenous tirofiban compared with placebo (adjusted risk ratio (RR), 1.51; 95% confidence interval (CI), 0.97–2.36; P  = 0.07). Subgroup analyses showed that age greater than 67-year-old (adjusted RR, 2.18; 95% CI 1.18–4.00), NIHSS greater than 16 (adjusted RR, 1.88; 95% CI 1.06–3.34), and cardioembolism (adjusted RR, 3.73; 95% CI 1.66–8.35) were associated with increased SICH risk. Conclusions In patients with acute large vessel occlusion stroke, intravenous tirofiban before EVT within 24 h of time from last known well is not associated with increased risk of SICH. Patients who are older, have more severe neurological deficits, or with cardioembolism are at higher risk of SICH with intravenous tirofiban. Trial registration number URL: http://www.chictr.org.cn ; Unique identifier: ChiCTR-INR-17014167.

Traumatic brain injury (TBI) is strongly associated with coagulopathy that occurs in 25–35% of patients. This complication is linked to higher mortality and morbidity. Recent lines of evidance have supported administration of fibrinogen concentrate (FC) in patients with severe TBI, while its efficacy remains controversial. In this study we aim to evaluate the effectiveness of serum fibrinogen level correction from 1.5 and 2.0 g/l to more than 2.0 g/l in patients with severe TBI undergoing traumatic cranial surgery. This randomized, single-blind, placebo-controlled clinical trial included trauma patients who had abbreviated injury scale (AIS) more than 3 in head and below 3 in other organs. FC was administered intravenously to patients with severe TBI undergoing TBI to correct the fibrinogen level above 2 g/l. Patients were randomly assigned to FC and control groups. The amount of intra-operative blood loss, packed cell (PC) transfusion, formation of new intracranial hemorrhage, and hemovac drainage were compared between the two study groups. Forty-seven of 65 participants received the study intervention within 40–112 min of admission. Intra-operative PC transfusion was higher in FC group (80%) compared to control group (55.5%) while the differance was not statistically significant (p > 0.05). Intra-operative blood loss was significantly higher in control group than FC group (P = 0.036). Chance of re-operation and new intracranial hematoma were not significantly different between two study groups. Early delivery of FC, decreases intraoperative bleeding. Although based on our findings it has no other effect on other parameters, further multicenter studies are recommended to investigate the role of early FC administration in management of post traumatic coagulopathy. •Early delivery of Fibrinogen concentrate, decreases intraoperative bleeding.•Fibrinogen has no other effect on other blood parameters.•Early administration of fibrinogen does not affect the prognosis of the patients with TBI.

High body temperature in the first 12–24 h after stroke onset is associated with poor functional outcome. The Paracetamol (Acetaminophen) In Stroke (PAIS) trial aimed to assess whether early treatment with paracetamol improves functional outcome in patients with acute stroke by reducing body temperature and preventing fever. In a multicentre, randomised, double-blind, placebo-controlled trial, patients with ischaemic stroke or intracerebral haemorrhage and body temperature between 36°C and 39°C were randomly assigned treatment with paracetamol (6 g daily) or placebo within 12 h from symptom onset. Treatment allocation was based on a computer-generated list of random numbers with varying block size. The primary outcome was improvement beyond expectation on the modified Rankin scale at 3 months, according to the sliding dichotomy approach. This trial is registered, number ISRCTN74418480. Between March, 2003, and May, 2008, 1400 patients were randomly allocated treatment. 260 (37%) of 697 patients receiving paracetamol and 232 (33%) of 703 receiving placebo improved beyond expectation (adjusted odds ratio [OR] 1·20, 95% CI 0·96–1·50). In a post-hoc analysis of patients with baseline body temperature 37–39°C, treatment with paracetamol was associated with improved outcome (1·43, 1·02–1·97). There were 55 serious adverse events in the paracetamol group (8%) and 70 in the placebo group (10%). These results do not support routine use of high-dose paracetamol in patients with acute stroke. Paracetamol might have a beneficial effect on functional outcome in patients admitted with a body temperature 37–39°C, but this post-hoc finding needs further study. Netherlands Heart Foundation.

Abstract BACKGROUND Traumatic brain injury (TBI) remains one of the most challenging health and socioeconomic problems of our times. Clinical courses may be complicated by hemostatic abnormalities either pre-existing or developing with TBI. OBJECTIVE To review frequencies, patterns, mechanisms, novel approaches to diagnostics, treatment, and outcomes of hemorrhagic progression and coagulopathy after TBI. METHODS Selective review of the literature in the databases Medline (PubMed) and Cochrane Reviews using different combinations of the relevant search terms was conducted. RESULTS Of the patients, 20% with isolated TBI display laboratory coagulopathy upon hospital admission with profound effect on morbidity and mortality. Preinjury use of antithrombotic agents may be associated with higher rates of hemorrhagic progression and delayed traumatic intracranial hemorrhage. Further testing may display various changes affecting platelet function/numbers, pro- and/or anticoagulant factors, and fibrinolysis as well as interactions between brain tissues, vascular endothelium, mechanisms of inflammation, and blood flow dynamics. The nature of hemostatic disruptions after TBI remains elusive but current evidence suggests the presence of both a hyper- and hypocoagulable state with possible overlap and lack of distinction between phases and states. More “global” hemostatic assays, eg, viscoelastic and thrombin generation tests, may provide more detailed and timely information on the overall hemostatic potential thereby allowing early “goal-directed” therapies. CONCLUSION Whether timely and targeted management of hemostatic abnormalities after TBI can protect against secondary brain injury and thereby improve outcomes remains elusive. Innovative technologies for diagnostics and monitoring offer windows of opportunities for precision medicine approaches to managing TBI.

Background Concomitant acute ischemic lesions are detected in up to a quarter of patients with spontaneous intracerebral hemorrhage (ICH). Influence of bleeding pattern and intraventricular hemorrhage (IVH) on risk of ischemic lesions has not been investigated. Methods Retrospective study of all 500 patients enrolled in the CLEAR III randomized controlled trial of thrombolytic removal of obstructive IVH using external ventricular drainage. The primary outcome measure was radiologically confirmed ischemic lesions, as reported by the Safety Event Committee and confirmed by two neurologists. We assessed predictors of ischemic lesions including analysis of bleeding patterns (ICH, IVH and subarachnoid hemorrhage) on computed tomography scans (CT). Secondary outcomes were blinded assessment of mortality and modified Rankin scale (mRS) at 30 and 180 days. Results Ischemic lesions occurred in 23 (4.6%) during first 30 days after ICH. Independent risk factors associated with ischemic lesions in logistic regression models adjusted for confounders were higher IVH volume ( p  = 0.004) and persistent subarachnoid hemorrhage on CT scan ( p  = 0.03). Patients with initial IVH volume ≥ 15 ml had five times the odds of concomitant ischemic lesions compared to IVH volume < 15 ml. Patients with ischemic lesions had significantly higher odds of death at 1 and 6 months (but not poor outcome; mRS 4–6) compared to patients without concurrent ischemic lesions. Conclusions Occurrence of ischemic lesions in the acute phase of IVH is not uncommon and is significantly associated with increased early and late mortality. Extra-parenchymal blood (larger IVH and visible subarachnoid hemorrhage) is a strong predictor for development of concomitant ischemic lesions after ICH.

We evaluated the acceptability of the Pediatric Quality of Life Inventory (PedsQL) and other outcomes as the primary outcomes for a pediatric hemorrhagic trauma trial (TIC-TOC) among clinicians. We conducted a mixed-methods study that included an electronic questionnaire followed by teleconference discussions. Participants confirmed or rejected the PedsQL as the primary outcome for the TIC-TOC trial and evaluated and proposed alternative primary outcomes. Responses were compiled and a list of themes and representative quotes was generated. 73 of 91 (80%) participants completed the questionnaire. 61 (84%) participants agreed that the PedsQL is an appropriate primary outcome for children with hemorrhagic brain injuries. 32 (44%) participants agreed that the PedsQL is an acceptable primary outcome for children with hemorrhagic torso injuries, 27 (38%) participants were neutral, and 13 (18%) participants disagreed. Several themes were identified from responses, including that the PedsQL is an important and patient-centered outcome but may be affected by other factors, and that intracranial hemorrhage progression assessed by brain imaging (among patients with brain injuries) or blood product transfusion requirements (among patients with torso injuries) may be more objective outcomes than the PedsQL. The PedsQL was a well-accepted proposed primary outcome for children with hemorrhagic brain injuries. Traumatic intracranial hemorrhage progression was favored by a subset of clinicians. A plurality of participants also considered the PedsQL an acceptable outcome for children with hemorrhagic torso injuries. Blood product transfusion requirement was favored by fewer participants. •Across a multidisciplinary cohort of clinicians, the PedsQL was a well-accepted outcome in a trial of injured children•Intracranial hemorrhage progression and blood transfusion requirement was favored by a smaller subset of clinicians•The main concern about the PedsQL as an outcome was it may be impacted by other factors outside of the study intervention