Hematoma Growth Research Articles

Anticoagulation therapy in atrial fibrillation after intracranial hemorrhage

Intracerebral hemorrhage (ICH) is severe and fatal complication of anticoagulant therapy with an incidence 0.3-0.7% per year. For patients with atrial fibrillation (AF) anticoagulants are administered for decreasing risk of stroke and systemic embolism. In this case the occurrence of intracranial bleeding is hard task for doctor. From the one side it is necessary to reverse the action of the drug for preventing the growth of hematoma. At the same time the discontinuation of therapy increases the risk of systemic embolism for patients with AF significantly. Clinical guidelines and studies have been reviewed about ICH during anticoagulant therapy. Nowadays there is no quality evidence about reversal of anticoagulant effects after ICH and optimal time of resumption of anticoagulant therapy. Firstly, we do not have large randomized controlled trials on this issue. The majority of clinical guidelines were based on retrospective studies and opinions of experts. Soon several randomized controlled trials will be finished and new data will be presented.

Melatonin attenuates microglial activation and improves neurological functions in rat model of collagenase-induced intracerebral hemorrhage

Intracerebral hemorrhage (ICH) is a severe form of stroke with a high mortality rate. It is also an important cause of permanent disability. Apart from hematoma growth and edema development, inflammatory responses and oxidative stress are responsible for poor outcomes after ICH. Due to its antioxidant, anti-inflammatory and anti-apoptotic properties, melatonin is a neuroprotective molecule against different neurological diseases. The protective roles of melatonin on ICH, particularly in the collagenase-induced ICH model, have not been well studied. The present study aims to explore neuroprotective effects of melatonin against ICH. At 24 hours after ICH induction, rats exhibited neurological deficits with mild loss in body weight (BW). Hematoma was found in the brain parenchyma with ED-1+ activated microglia and TUNEL+ apoptotic cells in the perihematomal region. As an in vitro model of ICH, SH-SY5Y cells were treated with red blood cell lysate. This treatment significantly reduced cell viability; however, melatonin (10-5 M) restored the cell viability. At 72 hours after ICH, rats treated with melatonin (50 mg/kg) at 2, 24 and 48 hours had reduced perihematomal microglial activation. However, there was no effect on hematoma size or perihematomal apoptosis. We further treated rats with 50 mg/kg melatonin starting at 2 hours and repeating at 24-hour intervals for two or seven more days. Both melatonin treatments improved post-ICH neurological functions, and the effect was most pronounced at 4 days after ICH. Since studies regarding the protective roles of melatonin on ICH remain very limited, our study advances our understanding of the potential use of melatonin as a treatment for ICH.

Predictors of Brain Natriuretic Peptide Serum Level Elevation in Patients with Symptomatic Chronic Subdural Hematoma: A Prospective Study.

Background: Brain natriuretic peptide serum levels (BNP) on admission are frequently elevated in patients with symptomatic chronic subdural hematoma (cSDH) and predict unfavorable long-term functional outcomes. However, the reasons for these elevated levels remain unclear. Therefore, we aimed to identify the predictors of BNP elevation. Methods: Patients with unilateral symptomatic cSDH who were surgically treated in our department between November 2016 and May 2020 were enrolled. Patients’ symptoms and neurological deficits were prospectively assessed using a study questionnaire. On initial computer tomography, hematoma volumes and midline shift (MLS) values were measured to analyze the degree of brain compression. Results: In total, 100 patients were analyzed. Linear regression analysis showed that higher BNP levels were significantly associated with smaller hematoma volumes (p = 0.003) and littler MLS values (p = 0.022). Multivariate analysis revealed that presence of a neurological deficit (p = 0.041), a hematoma volume < 140 mL (p = 0.047), advanced age (p = 0.023), and head trauma within 24 h of admission (p = 0.001) were independent predictors of BNP elevation. Conclusion: In symptomatic cSDH, BNP elevation is related, among others, to the presence of neurological deficits and smaller hematoma volumes. Whether BNP elevation may coincide with the early stage of hematoma growth, i.e., immaturity of cSDH neomembrane, requires further investigations.

Large cardiac wall hematoma with rapid growth: a case report of a potentially catastrophic complication during cardiac surgery

BackgroundRapid growth of cardiac wall hematoma is a rare but potentially fatal complication of cardiac surgery. However, its pathophysiology and optimal management remain undefined.Case presentationHere we present a rare case of a large cardiac wall hematoma in the right ventricle during a thoracic aortic and valvular surgery. The hematoma expanded rapidly with epicardial rupture during cardiopulmonary bypass. We could establish non-surgical hemostasis and prevent further expansion of hematoma by early weaning of the cardiopulmonary bypass, followed by the administration of protamine and manual compression by hemostatic agent application. His postoperative recovery was uneventful and upon computed tomography analysis, the hematoma was observed to have absorbed completely at 1 week postoperatively. The patient is doing well 1 year after the surgery without evidence of recurrent cardiac wall hematoma on follow-up computed tomography.ConclusionsCardiovascular surgeons should bear in mind this potentially catastrophic complication during cardiac surgery. Because of the vulnerability of the cardiac wall at the area of the hematoma, we believe that a hemostatic approach without sutures may be effective for this lethal complication.

Tranexamic acid for acute intracerebral haemorrhage growth based on imaging assessment (TRAIGE): a multicentre, randomised, placebo-controlled trial

BackgroundStudies show tranexamic acid can reduce the risk of death and early neurological deterioration after intracranial haemorrhage. We aimed to assess whether tranexamic acid reduces haematoma expansion and improves outcome...

Feasibility of a combined swirl and blending sign on non-contrast computed tomography for predicting early hematoma expansion after spontaneous intracerebral hemorrhage.

For predicting the hematoma expansion of spontaneous intracerebral hemorrhage, spot and swirl signs have been investigated. However, the clinical effectiveness of these signs remains debatable. These signs do not consider the peripheral hypodense lesions, which may imply a greater chance of ongoing bleedings. We proposed a new combined swirl and blending sign and evaluated its clinical usefulness in predicting hematoma expansion in non-contrast computed tomography settings. A total of 201 patients who were diagnosed with spontaneous intracerebral hemorrhage were enrolled. Their clinical and radiologic data were retrospectively reviewed. Patients were classified into hematoma expansion (N.=51) and nonexpansion groups (N.=150), and multivariable logistic regression analyses were performed to identify the factors associated with hematoma expansion. In the hematoma expansion group, an average of 20 mL of volume increase was noted. In multivariate analyses, several factors, including higher systolic blood pressure (P=0.026), larger initial hematoma volume (0.002), spot sign (0.019) and combined swirl and blending sign (<0.001), were identified as reliable predictors of hematoma expansion. A swirl (P=0.396) or blending sign (P=0.124) alone was not identified as a significant predictor of hematoma growth. The sensitivity, specificity, and positive and negative predictive values of the combined swirl and blending sign were 31%, 97%, 80%, and 81%, respectively. A newly defined "combined swirl and blending sign" on non-contrast computed tomography was positively associated with an increased risk of hematoma expansion of spontaneous intracerebral hemorrhage and could be regarded as a reliable predictor in non-contrast computed tomography settings.

Proposal of a prediction score for hematoma expansion after intracerebral hemorrhage

ObjectiveTo propose and validate a prediction score for intracerebral hemorrhage (ICH) patients at risk of hematoma expansion (HE). DesignA retrospective observational study was designed to propose and validate the score. SettingSanxiang Road branch and Xuguan branch belonging to the Second Affiliated Hospital of Soochow University (China). PatientsA total of 317 ICH patients in Sanxiang Road branch were registered as the development cohort, and 109 ICH patients in Xuguan branch were enrolled as the validation cohort. ProcedureIndependent risk factors for HE were identified using multiple logistic regression analysis. A prediction score was then proposed based on β coefficients and preliminarily verified in the validation cohort. Main variablesAll clinical data of the patients were compiled from the electronic medical records. Hematoma expansion was defined as an increase in hematoma volume >33% or absolute hematoma growth >6ml from the initial scan. Specific non-contrast CT(NCCT) signs were identified by two observers independently. ResultsOur score demonstrated satisfactory discrimination ability for HE (area under the ROC curve 0.854 in the development cohort versus 0.893 in the validation cohort). Appropriate calibration was found in the development cohort, whereas calibration in the validation cohort was slightly lower but still within the accuracy range (maximum deviation, average deviation and P were 0.070, 0.028, 0.773, respectively, versus 0.114, 0.056, 0.156). Decision curve analysis of the score from two samples were both far from the curve of treat all and curve of treat none, which verified its security and reliability. Patients with a total score ≥4.5 were at greatest risk of HE. ConclusionThe score may provide some reference and help in accurately identifying individuals at high risk of HE, allowing rapid guidance of clinical management and also serving as an aid in clinical trials.

STWEAK is a marker of early haematoma growth and leukoaraiosis in intracerebral haemorrhage

ObjectiveTo study the association between early growth of haematoma with biomarkers of endothelial dysfunction such as leukoaraiosis (LA) and the soluble tumour necrosis factor-like weak inducer of apoptosis (sTWEAK) in...

Abstract P422: Chronic Nicotine Exposure Increases Hematoma Growth Following Intracerebral Hemorrhage in Young Rats of Both Sexes

Spontaneous intracerebral hemorrhage (sICH) is the deadliest stroke subtype. There is strong evidence that tobacco use / smoking increases the risk of sICH, and some epidemiological studies have observed sex differences in sICH outcomes. However, systematic controlled studies on the effect of tobacco / smoking on post-sICH outcomes in both sexes are lacking. Therefore, we determined the effect of nicotine exposure on outcomes following collagenase-induced sICH both sexes. Young animals of both sexes were randomly divided into nicotine (4.5 mg / kg / day b.w.) and vehicle (saline) treatment groups (using osmotic pumps for two to three weeks). sICH in females was induced during the diestrous stage of estrous cycle. sICH was induced by collagenase injection into the right striatum and ~24 hours later, neurological scores were evaluated, rats were euthanized, and brains were sectioned to measure hematoma volume. Hematoma volumes for male rats was 42% higher (p&lt;0.01) in the nicotine-treated group (139 ± 9 mm 3 , n=10) versus vehicle-treated group (98 ± 9 mm 3 , n=10). Hematoma volumes for female rats was 48% higher (p&lt;0.01) in the nicotine-treated group (134 ± 11 mm 3 , n=10) versus vehicle-treated group (90 ± 7 mm 3 , n=10). Hematoma volumes for the vehicle and nicotine-treated male groups were not different from their respective female groups. The neurological score for the nicotine-treated male group (9.3 ± 0.6) was significantly higher (p&lt;0.05) when compared to vehicle group (7.4 ± 0.6). The neurological score for the nicotine-treated female group (10.7 ± 0.2) was significantly higher (p&lt;0.001) than the vehicle group (7.7 ± 0.7). The neurological score for the vehicle-treated male group was not different from its respective female group. However, the neurological score for the nicotine-treated male group was significantly lower than the female group. Our results show that chronic nicotine exposure increases hematoma volume post-sICH in animals of both sexes. Future studies into the mechanism of nicotine-induced increase in hematoma growth following sICH are required. Support: James and Esther King Biomedical Research Grant 9JK08

Abstract 40: Hematoma Expansion Shift Analysis to Assess Acute Intracerebral Hemorrhage Treatments

Background and Purpose: In present-day intracerebral hemorrhage (ICH) trials, hematoma expansion (HE) is often analyzed as a binary variable - present or absent. However, dichotomizing intrinsically wide-ranging variables discards substantial information reflective of treatment effect and can reduce the ability to detect relationships between the exposure and outcome of interest. We explored the concept of a “HE shift analysis” as a novel analytic mode for ICH treatment trials using previously published clinical trial data. Methods: Using data from the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-2) trial, patients were stratified by treatment status (intensive vs. standard blood pressure lowering with IV nicardipine) and HE shift was evaluated by generating strata based on a) previously established HE definitions, b) quartiles of 24-hour total hematoma volume, and c) quartiles of 24-hour total hematoma volume (THV) change. The relationship between blood pressure treatment and hematoma expansion shift was explored using proportional odds models and adjusted Wilcoxon testing. Results: The primary analysis population included 863 patients. In both treatment groups, approximately one-third of patients exhibited no hematoma growth. Using a conventional threshold, significant intraparenchymal expansion (≥33%) was reduced by 5.8% in those assigned to the intensive therapy arm (aOR: 0.77 [95% CI: 0.60-0.99], Figure 1A). The stratified quartiles of 24-hour total hematoma volumes were associated with a 5% shift within the highest and lowest strata in the intensive arm, (aOR: 0.83 [0.66-1.05], Figure 1B). Intensive therapy was associated with a 5.2% reduction from &gt; 3 mL to 0.5-3 mL (aOR: 0.86 [0.68-1.09], Figure 1C). Conclusions: A shift analysis model of HE provides additional insights into the biological effects of a given therapy and may be an alternate way to assess hemostatic agents in future hemorrhage trials.

Tobacco Use: A Major Risk Factor of Intracerebral Hemorrhage.

Spontaneous intracerebral hemorrhage (sICH) is one of the deadliest subtypes of stroke, and no treatment is currently available. One of the major risk factors is tobacco use. In this article, we review literature on how tobacco use affects the risk of sICH and also summarize the known effects of tobacco use on outcomes following sICH. Several studies demonstrate that the risk of sICH is higher in current cigarette smokers compared to non-smokers. The literature also establishes that cigarette smoking not only increases the risk of sICH but also increases hematoma growth, results in worse outcomes, and increases the risk of death from sICH. This review also discusses potential mechanisms activated by tobacco use which result in an increase in risk and severity of sICH. Exploring the underlying mechanisms may help alleviate the risk of sICH in tobacco users as well as may help better manage tobacco user sICH patients.

Nitric Oxide generating coating alters hematoma structure and soft tissue healing

IntroductionPeri-implantitis remains a major clinical problem due to the challenges in soft tissue integration on implants surfaces. During tissue healing processes, hematoma formation is the initial response to implant surfaces, which serves as a reservoir for growth factors and provides a natural scaffold for cell infiltration. However, little information is available regarding whether altering hematoma properties can benefit soft tissue healing and tissue integration. This study aims to modulate hematoma properties to create a friendly microenvironment for a strong soft tissue seal on implant surfaces. MethodsWe developed a polydopamine (PDAM) based coating capable of well-controlled nitric oxide (NO) generation by applying the copper (Cu) dose gradient. The incorporated copper with progressive raw concentrations of 10, 50 and 250µg/mL in the coating (PDAM@Cu coatings) served as a catalyst and reacted with endogenous NO donors in the blood. The resulting influence on clot structure and tissue healing microenvironment were analyzed along with its impact on the migration and proliferation of human gingival fibroblasts (HGFs). ResultsIt was noted that NO generation rates could be controlled using Cu from the coatings as a catalyst. As a result of this, the clot formation, structural properties, clot degradation, and growth factor release could be manipulated. Consequently, the NO generating surfaces of PDAM@Cu coating yielded a desired porous structure in clots and growth factor release profile, especially of platelet derived growth factors such as platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF). The NO generating surfaces of PDAM@Cu coating subsequently allowed increased migration and proliferation of HGFs. ConclusionIn this study, we developed a novel NO-generating strategy to regulate hematoma properties and growth factors release. The optimized coating could provide a favourable micro-environment for soft tissue healing and prompt cell migration and proliferation of HGFs. Therefore, PDAM surface modification with incorporation of Cu as a catalyst for NO generation could induce a functional implant surface for soft tissue integration.

Intracerebral Hemorrhage Hematoma Expansion Prediction with Deep Learning

Background: Hematoma expansion (HE) is associated with poor clinical outcomes following intracerebral hemorrhage (IcH). Existing predictors of HE from non-contrast computed tomography (NCCT) have low sensitivity and high inter-observer variability. Availability of an objective, standardized method to predict HE remains an unmet need. Methods: This multicenter observational cohort study analyzed a retrospective dataset of 2350 patients (December 2011 to June 2018, NCCT only, 86 centers), and a prospective dataset of 460 patients (March 2018 to February 2019, NCCT plus clinical data, 28 centers) with acute IcH . Prediction of HE, defined as a hematoma growth of > 6ml within 48 hours was the primary outcome of the study. A deep learning system (DLS) was developed and validated to autonomously predict HE based on the NCCT images using retrospectively collected data. A multivariate logistic regression model and a five-point score based on clinical variables and DLS prediction score were then developed using prospectively collected data. Findings: The DLS, using only NCCT, achieved HE prediction AUC of 0·783 (95% CI, 0·693-0·871) on the prospective validation dataset. Multivariate analysis of clinical variables indicated a higher risk of HE in patients with higher baseline NIHSS (OR: 4·37(1·56-12·25)), shorter onset-to-NCCT time (OR: 2·92(1·13-7·56)), and lack of antihypertensive therapy history (OR: 2·61 (1·05-6·53)) . Inclusion of these clinical variables along with DLS prediction, further improved the HE prediction accuracy, achieving an AUC of 0·812 (0·732-0·891) which was higher than all the previous methods. Finally, an easy-to-use five-point score was developed, which achieved an AUC of 0·789 (0·707-0·871). Interpretation: Deep learning systems could provide an automated, objective, multicenter generalizable, and observer bias-free solution for HE prediction from NCCT images. Inclusion of clinical factors may further improve the prediction accuracy and the system can be used to identify patients at risk of HE leading to a personalized treatment planning. Funding: Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, Beijing Municipal Committee of Science and Technology, Ministry of Science and Technology of the People’s Republic of China, National Natural Science Foundation of China, and Beijing Nova Program. Declaration of Interest: None to declare. Ethical Approval: This study was approved by the Institutional Review Board of Beijing TianTan hospital which covers all the hospitals contributing data to this study as part of the Chinese Stroke Center Alliance

Ultra-Early Venous Thromboembolism (VTE) Prophylaxis in Spontaneous Intracerebral Hemorrhage (sICH)

To determine if ultra-early (<24h) venous thromboembolism (VTE) prophylaxis was associated with hematoma growth in spontaneous intracerebral hemorrhage (ICH). Patients with ICH have a high risk of VTE. Pharmacological prophylaxis such as unfractionated heparin (UFH) have been demonstrated to reduce VTE. However, published datasets exclude patients with recent ICH out of concern for hematoma enlargement. American Heart/Stroke Association guidelines recommend UFH 1-4 days after hematoma stabilization while the European Stroke Organization has no recommendations on when to begin UFH. Our institutional practice is to obtain stability CT scans at 6 to 24h and to begin UFH following documented clinical and radiologic stability. We examined the impact of this practice on hematoma expansion. We performed a retrospective cohort analysis of consecutive ICH patients treated at a single tertiary academic referral center in the US. Demographic and clinical characteristics were abstracted. ICH volume was measured via 3D volumetrics for a CT head done on admission, follow-up stability, and prior to discharge. The primary outcome was analyzed as ≥3mL hematoma enlargement. Secondary outcomes include hematoma expansion of ≥6mL and ≥ 33%, length of stay (LOS), discharge disposition and mortality. A total of 163 ICH patients were analyzed. There were 58 (35.6%) patients in the ultra-early UFH group and UFH was initiated on average at 13.8h from initial scan. There were 105 (64.6%) patients in the standard group who initiated UFH at an average of 46.6h. The primary outcome of hematoma enlargement ≥3mL was observed in 2/58(3.4%) patients with ultra-early initiation of UFH and in 7/105(6.7%) in the standard group (p=0.49). Secondary outcomes were not significant including hematoma expansion in the ultra-early group ≥ 6mL 3/58 (5.2%) and ≥33% 7/58 (12.1%) (p=0.91, 0.61, respectively) as well as mortality or LOS. Venous thromboembolism prophylaxis started ultra-early (≤24h) after ICH was not associated with hematoma expansion.

Development and validation of a nomogram for predicting hematoma expansion in intracerebral hemorrhage

Background and objectiveTo develop and validate a clinical nomogram for individualized predicting hematoma expansion (HE) in patients with Intracerebral Hemorrhage (ICH). MethodsA total of 1025 patients with ICH were retrospectively enrolled in the development cohort between 2010 and 2016. We identified and integrated significant factors for HE to build a nomogram. The model was subjected to validation with a separate cohort of 397 patients from the 2017–2019. The predictive accuracy and discriminative ability were measured by concordance index (C-index). The primary outcome was HE, defined as hematoma growth more than 6 mL or 33% increase in the volume. ResultsA total of 1025 patients were included for univariable analysis. HE occurred in 180 patients (17.6%). The time to initial CT (≤6h vs. >6 h; p = 0.001), NIHSS score (0–4 vs. 5–14 vs. ≥15; p = 0.031), CTA spot sign (yes vs. no vs. absent; p = 0.018), hypodensities (p = 0.000), blend sign (p = 0.005), and INR (<1.2 vs. ≥1.2; p = 0.009) were identified and entered into the nomogram. The calibration curves for probability of HE showed optimal agreement between nomogram prediction and actual observation. The C-index was 0.751. The validation cohort consisted of 397 patients and HE occurred in 78 patients (19.6%). The C-index was 0.743. ConclusionsWe developed and validated a nomogram that can individually predict HE for ICH in Chinese populations. This practical prognostic nomogram may help clinicians make decision of clinical practice and design of clinical studies.

Clinical and radiological characteristics and outcome of wake-up intracerebral hemorrhage

There is little information on the characteristics of patients with wake-up intracerebral hemorrhage (WU-ICH). We aimed to evaluate frequency and relevant differences between WU-ICH and while-awake (WA) ICH patients. This is a retrospective study of a prospective database of consecutive patients with spontaneous ICH, who were classified as WU-ICH, WA-ICH or UO-ICH (unclear onset). We collected demographic, clinical and radiological data, prognostic and therapeutic variables, and outcome [(neurological deterioration, mortality, functional outcome (favorable when modified Rankin scale score 0–2)]. From a total of 466 patients, 98 (25.8%) were classified as UO-ICH according to the type of onset and therefore excluded. We studied 368 patients (mean age 73.9 ± 13.8, 51.4% men), and compared 95 (25.8%) WU-ICH with 273 (74.2%) WA-ICH. Patients from the WU-ICH group were significantly older than WA-ICH (76.9 ± 14.3 vs 72.8 ± 13.6, p = 0.01) but the vascular risk factors were similar. Compared to the WA-ICH group, patients from the WU-ICH group had a lower GCS score or a higher NIHSS score and a higher ICH score, and were less often admitted to a stroke unit or intensive care unit. There were no differences between groups in location, volume, rate of hematoma growth, frequency of intraventricular hemorrhage and outcome. One in five patients with spontaneous ICH are WU-ICH patients. Other than age, there are no relevant differences between WU and WA groups. Although WU-ICH is associated with worse prognostic markers vital and functional outcome is similar to WA-ICH patients.

Serum IgG titers against periodontal pathogens are associated with cerebral hemorrhage growth and 3-month outcome.

To assess the influence of periodontal disease on cerebral hemorrhage and its clinical course, we examined the association of the serum IgG titer of periodontal pathogens with hemorrhage growth and 3-month outcome. We consecutively enrolled 115 patients with acute cerebral hemorrhage (44 females, aged 71.3 ± 13.1 years) and used ELISA to evaluate the serum IgG titers of 9 periodontal pathogens: Porphyromonas gingivalis, Aggregatibacter (A.) actinomycetemcomitans, Prevotella intermedia, Prevotella nigrescens, Fusobacterium (F.) nucleatum, Treponema denticola, Tannerella forsythensis, Campylobacter rectus, and Eikenella corrodens. Significant hematoma growth was defined as an increase in the volume of >33% or an absolute increase in the volume of >12.5 mL. A poor outcome was defined as a 3 or higher on the modified Rankin Scale. We observed hemorrhage growth in 13 patients (11.3%). Multivariate analysis revealed that increased IgG titers of A. actinomycetemcomitans independently predicted the elevated hemorrhage growth (odds ratio 5.26, 95% confidence interval 1.52-18.25, p = 0.01). Notably, augmented IgG titers of F. nucleatum but not A. actinomycetemcomitans led to a poorer 3-month outcome (odds ratio 7.86, 95% confidence interval 1.08-57.08, p = 0.04). Thus, we demonstrate that elevated serum IgG titers of A. actinomycetemcomitans are an independent factor for predicting cerebral hemorrhage growth and that high serum IgG titers of F. nucleatum may predict a poor outcome in patients with this disease. Together, these novel data reveal how systemic periodontal pathogens may affect stroke patients, and, should, therefore, be taken into consideration in the management and treatment of these individuals.

Head down tilt 15° in experimental intracerebral hemorrhage: a randomized noninferiority safety trial.

Head down tilt 15° (HDT15°), applied before recanalization, increases collateral flow and improves outcome in experimental ischemic stroke. For its simplicity and low cost, HDT15° holds considerable potential to be developed as an emergency treatment of acute stroke in the prehospital setting, where hemorrhagic stroke is the major mimic of ischemic stroke. In this study, we assessed safety of HDT15° in the acute phase of experimental intracerebral hemorrhage. Intracerebral hemorrhage was produced by stereotaxic injection of collagenase in Wistar rats. A randomized noninferiority trial design was used to assign rats to HDT15° or flat position (n=64). HDT15° was applied for 1h during the time window of hematoma expansion. The primary outcome was hematoma volume at 24h. Secondary outcomes were mass effect, mortality, and functional deficit in the main study and acute changes of intracranial pressure, hematoma growth, and cardiorespiratory parameters in separate sets of randomized animals (n=32). HDT15° achieved the specified criteria of noninferiority for hematoma volume at 24h. Mass effect, mortality, and functional deficit at 24h showed no difference in the two groups. HDT15° induced a mild increase in intracranial pressure with respect to the pretreatment values (+2.91±1.76mmHg). HDT15° had a neutral effect on MRI-based analysis of hematoma growth and cardiorespiratory parameters. Application of HDT15° in the hyperacute phase of experimental intracerebral hemorrhage does not worsen early outcome. Further research is needed to implement HDT15° as an emergency collateral therapeutic for acute stroke.

Treatment of intracerebral hemorrhage: From specific interventions to bundles of care.

Intracerebral hemorrhage (ICH) represents a major, global, unmet health need with few treatments. A significant minority of ICH patients present taking an anticoagulant; both vitamin-K antagonists and increasingly direct oral anticoagulants. Anticoagulants are associated with an increased risk of hematoma expansion, and rapid reversal reduces this risk and may improve outcome. Vitamin-K antagonists are reversed with prothrombin complex concentrate, dabigatran with idarucizumab, and anti-Xa agents with PCC or andexanet alfa, where available. Blood pressure lowering may reduce hematoma growth and improve clinical outcomes and careful (avoiding reductions ≥60 mm Hg within 1 h), targeted (as low as 120–130 mm Hg), and sustained (minimizing variability) treatment during the first 24 h may be optimal for achieving better functional outcomes in mild-to-moderate severity acute ICH. Surgery for ICH may include hematoma evacuation and external ventricular drainage to treat hydrocephalus. No large, well-conducted phase III trial of surgery in ICH has so far shown overall benefit, but meta-analyses report an increased likelihood of good functional outcome and lower risk of death with surgery, compared to medical treatment only. Expert supportive care on a stroke unit or critical care unit improves outcomes. Early prognostication is difficult, and early do-not-resuscitate orders or withdrawal of active care should be used judiciously in the first 24–48 h of care. Implementation of acute ICH care can be challenging, and using a care bundle approach, with regular monitoring of data and improvement of care processes can ensure consistent and optimal care for all patients.

Sex differences in treatment, radiological features and outcome after intracerebral haemorrhage: Pooled analysis of Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage trials 1 and 2.

Reports vary on how sex influences the management and outcome from acute intracerebral haemorrhage. We aimed to quantify sex disparities in clinical characteristics, management, including response to blood pressure lowering treatment, and outcomes in patients with acute intracerebral haemorrhage, through interrogation of two large clinical trial databases. Post-hoc pooled analysis of the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage trials 1 and 2, where patients with a hypertensive response (systolic, 150-220 mmHg) after spontaneous intracerebral haemorrhage (<6 h) were randomised to intensive (target <140 mmHg <1 h) or guideline-recommended (<180 mmHg) blood pressure lowering treatment. The interaction of sex on early haematoma growth (24 h), death or major disability (modified Rankin scale scores 3-6 at 90 days), and effect of randomised treatment were determined in multivariable logistic regression models adjusted for baseline confounding variables. In 3233 participants, 1191 (37%) were women who were significantly older, had higher baseline National Institutes of Health Stroke Scale scores and smaller haematoma volumes compared to men. Men had higher three-month mortality (odds ratio 1.48, 95% confidence interval 1.10-2.00); however, there was no difference between women and men in the combined endpoint of death or major disability. There were no significant sex differences on mean haematoma growth or effect of randomised blood pressure lowering treatment. Men included in the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage trials had more comorbidities, larger baseline haematoma volumes and higher mortality after adjustment for age, as compared with women. Men included in the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage trials had a greater odds of dying after intracerebral haemorrhage than women, which could not be readily explained by differing casemix or patterns of blood pressure management. The Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage trials studies are registered with ClinicalTrials.gov (NCT00226096 and NCT00716079).