Neuroendoscopy-Assisted Entire-Process Visualization Technique of Ventricular Puncture for External Ventricular Drainage.

OBJECTIVE: This study aimed to investigate the feasibility, safety, and efficacy of the neuroendoscopy-assisted entire-process visualization technique (NEAEVT) of ventricular puncture for external ventricular drainage. METHODS: Eighty-eight patients with cerebral hemorrhage who underwent unilateral ventricular puncture for external ventricular drainage in our hospital from June 2021 to June 2023 were analyzed. Patients were grouped according to puncture technique: NEAEVT (30 patients), freehand (30 patients), and laser-navigation-assisted (28 patients). Operation time, drainage tube placement, and catheter-related hemorrhage incidence were compared between the groups. RESULTS: Mean operation time significantly differed between the freehand, NEAEVT, and laser-assisted groups (17.07, 18.37, and 34.04 min, respectively; P <0.0001). The position of the drainage tube was optimal or adequate in all patients of the NEAEVT group; optimal/adequate positioning was achieved in 80% of the freehand group. No catheter-related hemorrhage occurred in the NEAEVT group. Three freehand group patients and 2 laser-assisted group patients experienced catheter-related hemorrhage. CONCLUSION: The NEAEVT of ventricular puncture is accurate and achieves ventricular drainage without significantly increasing surgical trauma, operation time, or incidence of hemorrhage.

Prognostic biomarkers of intracerebral hemorrhage identified using targeted proteomics and machine learning algorithms.

Early prognostication of patient outcomes in intracerebral hemorrhage (ICH) is critical for patient care. We aim to investigate protein biomarkers' role in prognosticating outcomes in ICH patients. We assessed 22 protein biomarkers using targeted proteomics in serum samples obtained from the ICH patient dataset (N = 150). We defined poor outcomes as modified Rankin scale score of 3-6. We incorporated clinical variables and protein biomarkers in regression models and random forest-based machine learning algorithms to predict poor outcomes and mortality. We report Odds Ratio (OR) or Hazard Ratio (HR) with 95% Confidence Interval (CI). We used five-fold cross-validation and bootstrapping for internal validation of prediction models. We included 149 patients for 90-day and 144 patients with ICH for 180-day outcome analyses. In multivariable logistic regression, UCH-L1 (adjusted OR 9.23; 95%CI 2.41-35.33), alpha-2-macroglobulin (aOR 5.57; 95%CI 1.26-24.59), and Serpin-A11 (aOR 9.33; 95%CI 1.09-79.94) were independent predictors of 90-day poor outcome; MMP-2 (aOR 6.32; 95%CI 1.82-21.90) was independent predictor of 180-day poor outcome. In multivariable Cox regression models, IGFBP-3 (aHR 2.08; 95%CI 1.24-3.48) predicted 90-day and MMP-9 (aOR 1.98; 95%CI 1.19-3.32) predicted 180-day mortality. Machine learning identified additional predictors, including haptoglobin for poor outcomes and UCH-L1, APO-C1, and MMP-2 for mortality prediction. Overall, random forest models outperformed regression models for predicting 180-day poor outcomes (AUC 0.89), and 90-day (AUC 0.81) and 180-day mortality (AUC 0.81). Serum biomarkers independently predicted short-term poor outcomes and mortality after ICH. Further research utilizing a multi-omics platform and temporal profiling is needed to explore additional biomarkers and refine predictive models for ICH prognosis.

Emergent Management of Intracerebral Hemorrhage.

OBJECTIVE: Nontraumatic intracerebral hemorrhage (ICH) is a potentially devastating cerebrovascular disorder. Several randomized trials have assessed interventions to improve ICH outcomes. This article summarizes some of the recent developments in the emergent medical and surgical management of acute ICH. LATEST DEVELOPMENTS: Recent data have underscored the protracted course of recovery after ICH, particularly in patients with severe disability, cautioning against early nihilism and withholding of life-sustaining treatments. The treatment of ICH has undergone rapid evolution with the implementation of intensive blood pressure control, novel reversal strategies for coagulopathy, innovations in systems of care such as mobile stroke units for hyperacute ICH care, and the emergence of newer minimally invasive surgical approaches such as the endoport and endoscope-assisted evacuation techniques. ESSENTIAL POINTS: This review discusses the current state of evidence in ICH and its implications for practice, using case illustrations to highlight some of the nuances involved in the management of acute ICH.

Efficacy and safety of neuroendoscopy surgery versus craniotomy for supratentorial intracerebral hemorrhage: an updated meta-analysis of randomized controlled trials.

Neuroendoscopy (NE) surgery emerged as a promising technique for the treatment of spontaneous intracerebral hemorrhage (ICH). A previous meta-analysis of randomized controlled trials (RCTs) analyzed the efficacy and safety of NE compared to craniotomy, but NE did not present a significant improvement in functional outcomes. However, a new study provided an opportunity to update the current knowledge. We searched PubMed, Embase, and Cochrane Central Register of Controlled Trials for RCTs reporting NE evacuation of spontaneous supratentorial ICH compared to craniotomy. The efficacy outcomes of interest were favorable functional outcome, functional disability, hematoma evacuation rate, and residual hematoma volume. The safety outcomes of interest were rebleeding, infection, and mortality. Seven RCTs were included containing 879 patients. The NE approach presented a significantly higher rate of favorable functional outcome compared with craniotomy (RR: 1.42; 95% CI 1.17, 1.73; p < 0.001). The evacuation rate was higher in patients who underwent the NE approach (MD: -8.36; 95% CI -12.66, -4.07; p < 0.001). NE did not show a benefit in improving the mortality rate (RR: 0.81, 95% CI 0.54, 1.22; p = 0.32). NE was associated with more favorable functional outcomes and lower rates of functional disabilities compared to craniotomy. Also, NE was superior regarding evacuation rate, while presenting a reduction in residual hematoma volume. NE might be associated with lower infection rates. Mortality was not improved by NE surgery. Larger, higher-quality randomized studies are needed to adequately evaluate the efficacy and safety of NE compared to craniotomy.

Cumulative Systolic Blood Pressure and Incident Stroke Type Variation by Race and Ethnicity.

Importance: Stroke risk varies by systolic blood pressure (SBP), race, and ethnicity. The association between cumulative mean SBP and incident stroke type is unclear, and whether this association differs by race and ethnicity remains unknown. Objective: To examine the association between cumulative mean SBP and first incident stroke among 3 major stroke types-ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH)-and explore how these associations vary by race and ethnicity. Design, Setting, and Participants: Individual participant data from 6 US longitudinal cohorts (January 1, 1971, to December 31, 2019) were pooled. The analysis was performed from January 1, 2022, to January 2, 2024. The median follow-up was 21.6 (IQR, 13.6-31.8) years. Exposure: Time-dependent cumulative mean SBP. Main Outcomes and Measures: The primary outcome was time from baseline visit to first incident stroke. Secondary outcomes consisted of time to first incident IS, ICH, and SAH. Results: Among 40 016 participants, 38 167 who were 18 years or older at baseline with no history of stroke and at least 1 SBP measurement before the first incident stroke were included in the analysis. Of these, 54.0% were women; 25.0% were Black, 8.9% were Hispanic of any race, and 66.2% were White. The mean (SD) age at baseline was 53.4 (17.0) years and the mean (SD) SBP at baseline was 136.9 (20.4) mm Hg. A 10-mm Hg higher cumulative mean SBP was associated with a higher risk of overall stroke (hazard ratio [HR], 1.20 [95% CI, 1.18-1.23]), IS (HR, 1.20 [95% CI, 1.17-1.22]), and ICH (HR, 1.31 [95% CI, 1.25-1.38]) but not SAH (HR, 1.13 [95% CI, 0.99-1.29]; P = .06). Compared with White participants, Black participants had a higher risk of IS (HR, 1.20 [95% CI, 1.09-1.33]) and ICH (HR, 1.67 [95% CI, 1.30-2.13]) and Hispanic participants of any race had a higher risk of SAH (HR, 3.81 [95% CI, 1.29-11.22]). There was no consistent evidence that race and ethnicity modified the association of cumulative mean SBP with first incident stroke and stroke type. Conclusions and Relevance: The findings of this cohort study suggest that cumulative mean SBP was associated with incident stroke type, but the associations did not differ by race and ethnicity. Culturally informed stroke prevention programs should address modifiable risk factors such as SBP along with social determinants of health and structural inequities in society.

Predicting early mortality and severe intraventricular hemorrhage in very-low birth weight preterm infants: a nationwide, multicenter study using machine learning.

Our aim was to develop a machine learning-based predictor for early mortality and severe intraventricular hemorrhage (IVH) in very-low birth weight (VLBW) preterm infants in Taiwan. We collected retrospective data from VLBW infants, dividing them into two cohorts: one for model development and internal validation (Cohort 1, 2016-2021), and another for external validation (Cohort 2, 2022). Primary outcomes included early mortality, severe IVH, and early poor outcomes (a combination of both). Data preprocessing involved 23 variables, with the top four predictors identified as gestational age, birth body weight, 5-min Apgar score, and endotracheal tube ventilation. Six machine learning algorithms were employed. Among 7471 infants analyzed, the selected predictors consistently performed well across all outcomes. Logistic regression and neural network models showed the highest predictive performance (AUC 0.81-0.90 in both internal and external validation) and were well-calibrated, confirmed by calibration plots and the lowest two mean Brier scores (0.0685 and 0.0691). We developed a robust machine learning-based outcome predictor using only four accessible variables, offering valuable prognostic information for parents and aiding healthcare providers in decision-making.

Development of a time-resolved immunochromatographic test strip for rapid and quantitative determination of GFAP in serum.

Glial fibrillary acidic protein (GFAP) in serum has been shown as a biomarker of traumatic brain injury (TBI) which is a significant global public health concern. Accurate and rapid detection of serum GFAP is critical for TBI diagnosis. In this study, a time-resolved fluorescence immunochromatographic test strip (TRFIS) was proposed for the quantitative detection of serum GFAP. This TRFIS possessed excellent linearity ranging from 0.05 to 2.5 ng/mL for the detection of serum GFAP and displayed good linearity (Y = 598723X + 797198, R2 = 0.99), with the lowest detection limit of 16 pg/mL. This TRFIS allowed for quantitative detection of serum GFAP within 15 min and showed high specificity. The intra-batch coefficient of variation (CV) and the inter-batch CV were both < 4.0%. Additionally, this TRFIS was applied to detect GFAP in the serum samples from healthy donors and patients with cerebral hemorrhage, and the results of TRFIS could efficiently discern the patients with cerebral hemorrhage from the healthy donors. Our developed TRFIS has the characteristics of high sensitivity, high accuracy, and a wide linear range and is suitable for rapid and quantitative determination of serum GFAP on-site.

Andexanet for Factor Xa Inhibitor-Associated Acute Intracerebral Hemorrhage.

BACKGROUND: Patients with acute intracerebral hemorrhage who are receiving factor Xa inhibitors have a risk of hematoma expansion. The effect of andexanet alfa, an agent that reverses the effects of factor Xa inhibitors, on hematoma volume expansion has not been well studied. METHODS: We randomly assigned, in a 1:1 ratio, patients who had taken factor Xa inhibitors within 15 hours before having an acute intracerebral hemorrhage to receive andexanet or usual care. The primary end point was hemostatic efficacy, defined by expansion of the hematoma volume by 35% or less at 12 hours after baseline, an increase in the score on the National Institutes of Health Stroke Scale of less than 7 points (scores range from 0 to 42, with higher scores indicating worse neurologic deficit) at 12 hours, and no receipt of rescue therapy between 3 hours and 12 hours. Safety end points were thrombotic events and death. RESULTS: A total of 263 patients were assigned to receive andexanet, and 267 to receive usual care. Efficacy was assessed in an interim analysis that included 452 patients, and safety was analyzed in all 530 enrolled patients. Atrial fibrillation was the most common indication for factor Xa inhibitors. Of the patients receiving usual care, 85.5% received prothrombin complex concentrate. Hemostatic efficacy was achieved in 150 of 224 patients (67.0%) receiving andexanet and in 121 of 228 (53.1%) receiving usual care (adjusted difference, 13.4 percentage points; 95% confidence interval [CI], 4.6 to 22.2; P = 0.003). The median reduction from baseline to the 1-to-2-hour nadir in anti-factor Xa activity was 94.5% with andexanet and 26.9% with usual care (P<0.001). Thrombotic events occurred in 27 of 263 patients (10.3%) receiving andexanet and in 15 of 267 (5.6%) receiving usual care (difference, 4.6 percentage points; 95% CI, 0.1 to 9.2; P = 0.048); ischemic stroke occurred in 17 patients (6.5%) and 4 patients (1.5%), respectively. There were no appreciable differences between the groups in the score on the modified Rankin scale or in death within 30 days. CONCLUSIONS: Among patients with intracerebral hemorrhage who were receiving factor Xa inhibitors, andexanet resulted in better control of hematoma expansion than usual care but was associated with thrombotic events, including ischemic stroke. (Funded by Alexion AstraZeneca Rare Disease and others; ANNEXA-I ClinicalTrials.gov number, NCT03661528.).

TAK1 inhibition mitigates intracerebral hemorrhage-induced brain injury through reduction of oxidative stress and neuronal pyroptosis via the NRF2 signaling pathway.

Introduction: Intracerebral hemorrhage (ICH) often triggers oxidative stress through reactive oxygen species (ROS). Transforming growth factor-ß-activated kinase 1 (TAK1) plays a pivotal role in regulating oxidative stress and inflammation across various diseases. 5Z-7-Oxozeaenol (OZ), a specific inhibitor of TAK1, has exhibited therapeutic effects in various conditions. However, the impact of OZ following ICH and its underlying molecular mechanisms remain elusive. This study aimed to explore the possible role of OZ in ICH and its underlying mechanisms by inhibiting oxidative stress-mediated pyroptosis. Methods: Adult male Sprague-Dawley rats were subjected to an ICH model, followed by treatment with OZ. Neurobehavioral function, blood-brain barrier integrity, neuronal pyroptosis, and oxidative stress markers were assessed using various techniques including behavioral tests, immunofluorescence staining, western blotting, transmission electron microscopy, and biochemical assays. Results: Our study revealed that OZ administration significantly inhibited phosphorylated TAK1 expression post-ICH. Furthermore, TAK1 blockade by OZ attenuated blood-brain barrier (BBB) disruption, neuroinflammation, and oxidative damage while enhancing neurobehavioral function. Mechanistically, OZ administration markedly reduced ROS production and oxidative stress by facilitating nuclear factor-erythroid 2-related factor 2 (NRF2) nuclear translocation. This was accompanied by a subsequent suppression of the NOD-like receptor protein 3 (NLRP3) activation-mediated inflammatory cascade and neuronal pyroptosis. Discussion: Our findings highlight that OZ alleviates brain injury and oxidative stress-mediated pyroptosis via the NRF2 pathway. Inhibition of TAK1 emerges as a promising approach for managing ICH.

Signature and function of plasma exosome-derived circular RNAs in patients with hypertensive intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is one of the major causes of death and disability, and hypertensive ICH (HICH) is the most common type of ICH. Currently, the outcomes of HICH patients remain poor after treatment, and early prognosis prediction of HICH is important. However, there are limited effective clinical treatments and biomarkers for HICH patients. Although circRNA has been widely studied in diseases, the role of plasma exosomal circRNAs in HICH remains unknown. The present study was conducted to investigate the characteristics and function of plasma exosomal circRNAs in six HICH patients using circRNA microarray and bioinformatics analysis. The results showed that there were 499 differentially expressed exosomal circRNAs between the HICH patients and control subjects. According to GO annotation and KEGG pathway analyses, the targets regulated by differentially expressed exosomal circRNAs were tightly related to the development of HICH via nerve/neuronal growth, neuroinflammation and endothelial homeostasis. And the differentially expressed exosomal circRNAs could mainly bind to four RNA-binding proteins (EIF4A3, FMRP, AGO2 and HUR). Moreover, of differentially expressed exosomal circRNAs, hsa_circ_00054843, hsa_circ_0010493 and hsa_circ_00090516 were significantly associated with bleeding volume and Glasgow Coma Scale score of the subjects. Our findings firstly revealed that the plasma exosomal circRNAs are significantly involved in the progression of HICH, and could be potent biomarkers for HICH. This provides the basis for further research to pinpoint the best biomarkers and illustrate the mechanism of exosomal circRNAs in HICH.

Paroxysmal sympathetic hyperexcitability after brain injury: A clinical analysis of case series.

BACKGROUND: Paroxysmal sympathetic hyperexcitability (PSH) is a group of complex syndromes with various etiologies. Previous studies were limited to the description of traumatic brain injury (TBI), and the description of PSH after other types of brain injury was rare. We explored the clinical features, treatment, and prognosis of PSH after various types of brain injuries. METHODS: Patients admitted to the neurosurgery intensive care unit with PSH after brain injury from July 2019 to December 2022 were included. Demographic data, clinical manifestations, drug therapy, and disease prognosis were retrospectively collected and analyzed. RESULTS: Fifteen male and 9 female patients with PSH after brain injury were selected. TBI was most likely to cause PSH (66.7%), followed by spontaneous intracerebral hemorrhage (25%). Glasgow coma scale scores of 19 patients (79.2%) were lower than 8 and 14 patients (58.3%) underwent tracheotomy. Electroencephalogram monitoring was performed in 12 individuals, none of which showed epileptic waves. Clinical symptom scale showed mild symptoms in 17 cases (70.8%). Almost all patients were administered a combination of drugs. After follow-up, most patients had a poor prognosis and 2 (8.3%) died after discharge. CONCLUSION: The etiology of PSH is complex. TBI may be the most common cause of PSH. Non-TBI may also be an important cause of PSH. Therefore, early identification, prevention and diagnosis are helpful for determining the prognosis and outcome of the disease.

Identifying potential (re)hemorrhage among sporadic cerebral cavernous malformations using machine learning.

The (re)hemorrhage in patients with sporadic cerebral cavernous malformations (CCM) was the primary aim for CCM management. However, accurately identifying the potential (re)hemorrhage among sporadic CCM patients in advance remains a challenge. This study aims to develop machine learning models to detect potential (re)hemorrhage in sporadic CCM patients. This study was based on a dataset of 731 sporadic CCM patients in open data platform Dryad. Sporadic CCM patients were followed up 5 years from January 2003 to December 2018. Support vector machine (SVM), stacked generalization, and extreme gradient boosting (XGBoost) were used to construct models. The performance of models was evaluated by area under receiver operating characteristic curves (AUROC), area under the precision-recall curve (PR-AUC) and other metrics. A total of 517 patients with sporadic CCM were included (330 female [63.8%], mean [SD] age at diagnosis, 42.1 [15.5] years). 76 (re)hemorrhage (14.7%) occurred during follow-up. Among 3 machine learning models, XGBoost model yielded the highest mean (SD) AUROC (0.87 [0.06]) in cross-validation. The top 4 features of XGBoost model were ranked with SHAP (SHapley Additive exPlanations). All-Elements XGBoost model achieved an AUROCs of 0.84 and PR-AUC of 0.49 in testing set, with a sensitivity of 0.86 and a specificity of 0.76. Importantly, 4-Elements XGBoost model developed using top 4 features got a AUROCs of 0.83 and PR-AUC of 0.40, a sensitivity of 0.79, and a specificity of 0.72 in testing set. Two machine learning-based models achieved accurate performance in identifying potential (re)hemorrhages within 5 years in sporadic CCM patients. These models may provide insights for clinical decision-making.

Predicting severe intraventricular hemorrhage or early death using machine learning algorithms in VLBWI of the Korean Neonatal Network Database.

Severe intraventricular hemorrhage (IVH) in premature infants can lead to serious neurological complications. This retrospective cohort study used the Korean Neonatal Network (KNN) dataset to develop prediction models for severe IVH or early death in very-low-birth-weight infants (VLBWIs) using machine-learning algorithms. The study included VLBWIs registered in the KNN database. The outcome was the diagnosis of IVH Grades 3-4 or death within one week of birth. Predictors were categorized into three groups based on their observed stage during the perinatal period. The dataset was divided into derivation and validation sets at an 8:2 ratio. Models were built using Logistic Regression with Ridge Regulation (LR), Random Forest, and eXtreme Gradient Boosting (XGB). Stage 1 models, based on predictors observed before birth, exhibited similar performance. Stage 2 models, based on predictors observed up to one hour after birth, showed improved performance in all models compared to Stage 1 models. Stage 3 models, based on predictors observed up to one week after birth, showed the best performance, particularly in the XGB model. Its integration into treatment and management protocols can potentially reduce the incidence of permanent brain injury caused by IVH during the early stages of birth.

Red cell distribution width to lymphocyte ratio could serve as a new inflammatory biomarker for predicting hematoma expansion in patients with intracerebral hemorrhage.

BACKGROUND: Hematoma expansion is a critical factor associated with increased mortality and adverse outcomes in patients with intracerebral hemorrhage (ICH). Identifying and preventing hematoma expansion early on is crucial for effective therapeutic intervention. This study aimed to investigate the potential association between the Red cell distribution width to lymphocyte ratio (RDWLR) and hematoma expansion in ICH patients. METHODS: We conducted a retrospective analysis of clinical data from 303 ICH patients treated at our department between May 2018 and May 2023. Demographic, clinical, radiological, and laboratory data, including RDWLR upon admission, were assessed. Binary logistic regression analysis was employed to determine independent associations between various variables and hematoma expansion. RESULTS: The study included 303 ICH patients, comprising 167 (55.1%) males and 136 (44.9%) females, with a mean age of 65.25 ± 7.32 years at admission. Hematoma expansion occurred in 73 (24.1%) cases. Multivariate analysis revealed correlations between hematoma volume at baseline (OR, 2.73; 95% CI: 1.45 -4,78; P < 0.001), admission systolic blood pressure (OR, 2.98 ; 95% CI: 1.54-4.98; P < 0.001), Glasgow Coma Scale (GCS) (OR, 1.58; 95% CI: 1.25-2.46; P = 0.017), and RDWLR (OR, 1.58; 95% CI: 1.13-2.85; P = 0.022) and hematoma expansion in these patients. CONCLUSIONS: Our findings suggest that RDWLR could serve as a new inflammatory biomarker for hematoma expansion in ICH patients. This cost-effective and readily available biomarker has the potential for early prediction of hematoma expansion in these patients.

Association of Antithrombotic Drug Use With Incident Intracerebral Hemorrhage Location.

BACKGROUND AND OBJECTIVES: Few population-based studies have assessed associations between the use of antithrombotic (platelet antiaggregant or anticoagulant) drugs and location-specific risks of spontaneous intracerebral hemorrhage (s-ICH). In this study, we estimated associations between antithrombotic drug use and the risk of lobar vs nonlobar incident s-ICH. METHODS: Using Danish nationwide registries, we identified cases in the Southern Denmark Region of first-ever s-ICH in patients aged 50 years or older between 2009 and 2018. Each verified case was classified as lobar or nonlobar s-ICH and matched to controls in the general population by age, sex, and calendar year. Prior antithrombotic use was ascertained from a nationwide prescription registry. We calculated odds ratios (aORs) for associations between the use of clopidogrel, aspirin, direct oral anticoagulants (DOACs) or vitamin K antagonists (VKA), and lobar and nonlobar ICH in conditional logistic regression analyses that were adjusted for potential confounders. RESULTS: A total of 1,040 cases of lobar (47.9% men, mean age [SD] 75.2 [10.7] years) and 1,263 cases of nonlobar s-ICH (54.2% men, mean age 73.6 [11.4] years) were matched to 41,651 and 50,574 controls, respectively. A stronger association with lobar s-ICH was found for clopidogrel (cases: 7.6%, controls: 3.5%; aOR 3.46 [95% CI 2.45-4.89]) vs aspirin (cases: 22.9%, controls: 20.4%; aOR 2.14 [1.74-2.63; p = 0.019). Corresponding estimates for nonlobar s-ICH were not different between clopidogrel (cases: 5.4%, controls: 3.4%; aOR 2.44 [1.71-3.49]) and aspirin (cases: 20.7%, controls: 19.2%; aOR 1.77 [1.47-2.15]; p = 0.12). VKA use was associated with higher odds of both lobar (cases: 14.3%, controls: 6.1%; aOR 3.66 [2.78-4.80]) and nonlobar (cases: 15.4%, controls: 5.5%; aOR 4.62 [3.67-5.82]) s-ICH. The association of DOAC use with lobar s-ICH (cases: 3.5%, controls: 2.7%; aOR 1.66 [1.02-2.70]) was weaker than that of VKA use (p = 0.006). Corresponding estimates for nonlobar s-ICH were not different between DOACs (cases: 5.1%, controls: 2.4%; aOR 3.44 [2.33-5.08]) and VKAs (p = 0.20). DISCUSSION: Antithrombotics were associated with higher risks of s-ICH, but the strength of the associations varied by s-ICH location and drug, which may reflect differences in the cerebral microangiopathies associated with lobar vs nonlobar hemorrhages and the mechanisms of drug action.

Traditional and Non-Traditional Lipid Parameters in Relation to Parenchymal Hemorrhage Following Endovascular Treatment for Acute Ischemic Stroke in Anterior Circulation.

Purpose: Lipid-lowering therapy is integral in acute ischemic stroke (AIS), yet the connection between lipid parameters and parenchymal hemorrhage (PH) after endovascular treatment (EVT) for AIS is not well-defined. This research aims to assess the association between various lipid parameters and the PH risk following EVT. Patients and Methods: We examined a database of patients who underwent EVT for AIS between September 2021 and May 2023 retrospectively. Traditional and non-traditional lipid parameters were documented. PH was identified on dual energy computed tomography images within 48 h. We employed logistic regression analysis and restricted cubic splines to examine the association between various lipid parameters and the risk of PH. The predictive capacity of the lipid parameters for PH was evaluated by comparing the area under the curve. Results: The study included 384 patients, 65 of whom (17.7%) developed PH. After adjusting for potential confounders, only triglyceride was associated with PH among the traditional lipid parameters, while all non-traditional lipid parameters were related to PH. Based on ROC curve, the ratio of remnant cholesterol to high-density lipoprotein cholesterol (RC/HDL-C) exhibited the highest predictive capability for PH. Furthermore, our analysis revealed a significant nonlinear correlation between triglyceride, non-high-density lipoprotein cholesterol, RC, RC/HDL-C and PH risk. Conclusion: In assessing the risk of PH after EVT, non-traditional lipid parameters are often superior to traditional lipid parameters. It is recommended that routine evaluation of non-traditional lipid parameters could also be conducted in clinical practice as well.

Reversal or Repletion Treatment Strategies and Outcomes of Patients With Major Bleeding Events Managed in the Emergency Department: Large Real-Life Investigation in the Northwestern Healthcare District of Tuscany.

OBJECTIVE: To verify the incidence of bleeding events in patients on ongoing anticoagulant treatment in the real world and compare the results of different reversal or repletion strategies currently available for pharmacological treatment. METHODS: Patients managed in the emergency department (ED) with major bleeding events, on ongoing anticoagulation were stratified according to bleeding site and reversal or repletion therapy with andexanet alfa (ADX), idarucizumab (IDA), prothrombin complex concentrate (PCC), and vitamin K (Vit-K). ENDPOINT: Death at 30 days was compared in the subgroups with cerebral hemorrhage (CH) and gastrointestinal (GI) bleeding. RESULTS: Of the 809,397 visits in the years 2022-2023 at 6 EDs in the northwestern health district of Tuscany, 5372 patients with bleeding events were considered; 3740 were excluded due to minor bleeding or propensity score matching. Of the remaining 1632 patients with major bleeding, 548 on ongoing anticoagulation were enrolled; 334 received reversal or repletion agents. Patients with CH (n = 176) and GI bleeding (n = 108) represented the primary analysis cohorts in the study's strategic treatment assessment. Overall, 30-day survival of patients on ongoing aFXa treatment receiving on-label ADX versus off-label PCC showed a relative increase of 71%, while 30-day survival of patients on ongoing aFII receiving on-label IDA versus off-label PCC showed a relative increase of 30%; no substantial difference was found when comparing on-label PCC combined with Vit-K versus off-label Vit-K alone. Indeed, patients undergoing on-label ADX or IDA showed a statistically significant difference over off-label PCC (ADX vs. PCC: n = 15, events = 4, mean ± SD 82.50 ± 18.9, vs. 49, 13, 98.82 ± 27, respectively; analysis of variance [ANOVA] variance 8627; P < 0.001; posthoc test diff 32, 95% confidence interval: 28-35; P < 001; IDA vs. PCC: 20, 5, 32.29 ± 15.0 vs. 2, 1, 28.00 ± 0.0, respectively; ANOVA 1484; P < 0.001; posthoc test -29, -29 -29, respectively; P = n.d.). On-label PCC combined with Vit-K showed overall a slight statistically significant difference versus off-label Vit-K alone (52, 16, 100.58 ± 22.6 vs. 53, 11, 154.62 ± 29.8, respectively; ANOVA 310; P < 0.02; posthoc test 4, 0.7-7.2, respectively; P < 0.02). Data were confirmed in the group of patients with CH (ADX vs. PCC: n = 13, events = 3, mean ± SD 91.55 ± 18.6 vs. 78, 21, 108.91 ± 20.9, respectively; ANOVA variance 10,091, F = 261; P < 0.001; posthoc difference test 36, 95% confidence interval: 30-41; P < 0.001; IDA vs. PCC: 10, 2, 4.50 ± 2.5 vs. 78, 21, 108.91 ± 20.9, respectively; ANOVA 16,876,303, respectively; P < 0.001; posthoc test 41, 34-47, respectively; P < 0.001). On-label PCC combined with Vit-K showed an overall slight statistically significant difference compared with off-label Vit-K alone (P < 0.01 and P < 0.001 in the subgroups of CH and GI bleeding). CONCLUSIONS: Patients undergoing specific reversal therapy with on-label ADX or IDA, when treated with aFXa or aFII anticoagulants, respectively, showed statistically elevated differences in 30-day death compared with off-label repletion therapy with PCC. Overall, 30-day survival of patients on ongoing aFXa or aFII receiving on-label reversal therapy with ADX or IDA compared with off-label PCC repletion agents showed an increase of 71% and 30%, respectively.

Risk Factors for Intracerebral Hemorrhage: Genome-Wide Association Study and Mendelian Randomization Analyses.

BACKGROUND: The genetic and nongenetic causes of intracerebral hemorrhage (ICH) remain obscure. The present study aimed to uncover the genetic and modifiable risk factors for ICH. METHODS: We meta-analyzed genome-wide association study data from 3 European biobanks, involving 7605 ICH cases and 711 818 noncases, to identify the genomic loci linked to ICH. To uncover the potential causal associations of cardiometabolic and lifestyle factors with ICH, we performed Mendelian randomization analyses using genetic instruments identified in previous genome-wide association studies of the exposures and ICH data from the present genome-wide association study meta-analysis. We performed multivariable Mendelian randomization analyses to examine the independent associations of the identified risk factors with ICH and evaluate potential mediating pathways. RESULTS: We identified 1 ICH risk locus, located at the APOE genomic region. The lead variant in this locus was rs429358 (chr19:45411941), which was associated with an odds ratio of ICH of 1.17 (95% CI, 1.11-1.20; P=6.01×10-11) per C allele. Genetically predicted higher levels of body mass index, visceral adiposity, diastolic blood pressure, systolic blood pressure, and lifetime smoking index, as well as genetic liability to type 2 diabetes, were associated with higher odds of ICH after multiple testing corrections. Additionally, a genetic increase in waist-to-hip ratio and liability to smoking initiation were consistently associated with ICH, albeit at the nominal significance level (P<0.05). Multivariable Mendelian randomization analysis showed that the association between body mass index and ICH was attenuated on adjustment for type 2 diabetes and further that type 2 diabetes may be a mediator of the body mass index-ICH relationship. CONCLUSIONS: Our findings indicate that the APOE locus contributes to ICH genetic susceptibility in European populations. Excess adiposity, elevated blood pressure, type 2 diabetes, and smoking were identified as the chief modifiable cardiometabolic and lifestyle factors for ICH.

Machine learning models for predicting early hemorrhage progression in traumatic brain injury.

This study explores the progression of intracerebral hemorrhage (ICH) in patients with mild to moderate traumatic brain injury (TBI). It aims to predict the risk of ICH progression using initial CT scans and identify clinical factors associated with this progression. A retrospective analysis of TBI patients between January 2010 and December 2021 was performed, focusing on initial CT evaluations and demographic, comorbid, and medical history data. ICH was categorized into intraparenchymal hemorrhage (IPH), petechial hemorrhage (PH), and subarachnoid hemorrhage (SAH). Within our study cohort, we identified a 22.2% progression rate of ICH among 650 TBI patients. The Random Forest algorithm identified variables such as petechial hemorrhage (PH) and countercoup injury as significant predictors of ICH progression. The XGBoost algorithm, incorporating key variables identified through SHAP values, demonstrated robust performance, achieving an AUC of 0.9. Additionally, an individual risk assessment diagram, utilizing significant SHAP values, visually represented the impact of each variable on the risk of ICH progression, providing personalized risk profiles. This approach, highlighted by an AUC of 0.913, underscores the model's precision in predicting ICH progression, marking a significant step towards enhancing TBI patient management through early identification of ICH progression risks.

Improved differentiation of cavernous malformation and acute intraparenchymal hemorrhage on CT using an AI algorithm.

This study aimed to evaluate the utility of an artificial intelligence (AI) algorithm in differentiating between cerebral cavernous malformation (CCM) and acute intraparenchymal hemorrhage (AIH) on brain computed tomography (CT). A retrospective, multireader, randomized study was conducted to validate the performance of an AI algorithm in differentiating AIH from CCM on brain CT. CT images of CM and AIH (< 3 cm) were identified from the database. Six blinded reviewers, including two neuroradiologists, two radiology residents, and two emergency department physicians, evaluated CT images from 288 patients (CCM, n = 173; AIH, n = 115) with and without AI assistance, comparing diagnostic performance. Brain CT interpretation with AI assistance resulted in significantly higher diagnostic accuracy than without (86.92% vs. 79.86%, p < 0.001). Radiology residents and emergency department physicians showed significantly improved accuracy of CT interpretation with AI assistance than without (84.21% vs. 75.35%, 80.73% vs. 72.57%; respectively, p < 0.05). Neuroradiologists showed a trend of higher accuracy with AI assistance in the interpretation but lacked statistical significance (95.83% vs. 91.67%, p = 0.56). The use of an AI algorithm can enhance the differentiation of AIH from CCM in brain CT interpretation, particularly for nonexperts in neuroradiology.