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.

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.

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.

Antithrombotic Treatment and Clinical Outcomes After Intracerebral Hemorrhage: A Retrospective Cohort Study from the Swedish Stroke Register.

BACKGROUND: A rapid shift has occurred from vitamin K antagonists toward direct oral anticoagulants, which have a lower risk of intracerebral hemorrhage (ICH). However, effects on clinical outcomes after ICH are understudied. We aimed to describe the prevalence of antithrombotic drugs and to study the prognosis among prestroke functionally independent Swedish patients with ICH. METHODS AND RESULTS: We identified all patients diagnosed with nontraumatic ICH in 2017 to 2021 from the Swedish Stroke Register (n=13 155) and assessed death and functional outcome at 3 months after ICH in prestroke functionally independent patients (n=10 014). Functional outcome was estimated among 3-month survivors on the basis of self-reported activities of daily living scores. Risks of outcomes were estimated using Poisson regression. In 13 155 patients, 14.5% used direct oral anticoagulant, 10.1% vitamin K antagonists, and 21.6% antiplatelets at ICH onset. Among 10 014 pre-stroke activities of daily living-independent patients, oral anticoagulants and antiplatelets were associated with increased mortality risk (adjusted risk ratio, 1.27 [95% CI, 1.13-1.43]; P<0.001; and adjusted risk ratio, 1.23 [95% CI, 1.13-1.34]; P<0.001 respectively). Mortality risk did not statistically differ between antiplatelets and oral anticoagulants nor between direct oral anticoagulant and vitamin K antagonists. Among 5126 patients with nonmissing functional outcome (69.1% of survivors), antiplatelets (adjusted risk ratio, 1.06 [95% CI, 0.99-1.13]; P=0.100) and oral anticoagulants (adjusted risk ratio, 1.01 [95% CI, 0.92-1.12]; P=0.768) were not statistically significantly associated with functional dependence. CONCLUSIONS: There was no statistically significant difference in mortality risk between direct oral anticoagulant and vitamin K antagonists in prestroke functionally independent patients (unadjusted for oral anticoagulant class indication). Furthermore, mortality risk in antiplatelet and oral anticoagulant users might differ less than previously suggested.

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.

Association of large core middle cerebral artery stroke and hemorrhagic transformation with hospitalization outcomes.

Historically, investigators have not differentiated between patients with and without hemorrhagic transformation (HT) in large core ischemic stroke at risk for life-threatening mass effect (LTME) from cerebral edema. Our objective was to determine whether LTME occurs faster in those with HT compared to those without. We conducted a two-center retrospective study of patients with ≥ 1/2 MCA territory infarct between 2006 and 2021. We tested the association of time-to-LTME and HT subtype (parenchymal, petechial) using Cox regression, controlling for age, mean arterial pressure, glucose, tissue plasminogen activator, mechanical thrombectomy, National Institute of Health Stroke Scale, antiplatelets, anticoagulation, temperature, and stroke side. Secondary and exploratory outcomes included mass effect-related death, all-cause death, disposition, and decompressive hemicraniectomy. Of 840 patients, 358 (42.6%) had no HT, 403 (48.0%) patients had petechial HT, and 79 (9.4%) patients had parenchymal HT. LTME occurred in 317 (37.7%) and 100 (11.9%) had mass effect-related deaths. Parenchymal (HR 8.24, 95% CI 5.46-12.42, p < 0.01) and petechial HT (HR 2.47, 95% CI 1.92-3.17, p < 0.01) were significantly associated with time-to-LTME and mass effect-related death. Understanding different risk factors and sequelae of mass effect with and without HT is critical for informed clinical decisions.

Triglyceride-glucose index as a potential predictor for in-hospital mortality in critically ill patients with intracerebral hemorrhage: a multicenter, case-control study.

BACKGROUND: The correlation between the triglyceride-glucose index (TyG) and the prognosis of ischemic stroke has been well established. This study aims to assess the influence of the TyG index on the clinical outcomes of critically ill individuals suffering from intracerebral hemorrhage (ICH). METHODS: Patients diagnosed with ICH were retrospectively retrieved from the Medical Information Mart for Intensive Care (MIMIC-IV) and the eICU Collaborative Research Database (eICU-CRD). Various statistical methods, including restricted cubic spline (RCS) regression, multivariable logistic regression, subgroup analysis, and sensitivity analysis, were employed to examine the relationship between the TyG index and the primary outcomes of ICH. RESULTS: A total of 791 patients from MIMIC-IV and 1,113 ones from eICU-CRD were analyzed. In MIMIC-IV, the in-hospital and ICU mortality rates were 14% and 10%, respectively, while in eICU-CRD, they were 16% and 8%. Results of the RCS regression revealed a consistent linear relationship between the TyG index and the risk of in-hospital and ICU mortality across the entire study population of both databases. Logistic regression analysis revealed a significant positive association between the TyG index and the likelihood of in-hospital and ICU death among ICH patients in both databases. Subgroup and sensitivity analysis further revealed an interaction between patients' age and the TyG index in relation to in-hospital and ICU mortality among ICH patients. Notably, for patients over 60 years old, the association between the TyG index and the risk of in-hospital and ICU mortality was more pronounced compared to the overall study population in both MIMIC-IV and eICU-CRD databases, suggesting a synergistic effect between old age (over 60 years) and the TyG index on the in-hospital and ICU mortality of patients with ICH. CONCLUSIONS: This study established a positive correlation between the TyG index and the risk of in-hospital and ICU mortality in patients over 60 years who diagnosed with ICH, suggesting that the TyG index holds promise as an indicator for risk stratification in this patient population.

Anticoagulation therapy in non-valvular atrial fibrillation after intracerebral hemorrhage: A propensity score-matched study.

BACKGROUND: The effect of antithrombotic therapy on patients with atrial fibrillation who sustained previous intracerebral hemorrhage (ICH) remains uncertain. Data regarding antithrombotic therapy use in these patients are limited. This study aims to compare the clinical and overall outcomes of antithrombotic therapy and usual care in patients with atrial fibrillation who sustained ICH. METHODS: We assembled consecutive patients with atrial fibrillation sustaining an ICH from our institution. Multivariable regression analysis and propensity-matched analysis were applied to assess associations of different antithrombotic therapies and outcomes. The primary outcome was mortality within the longest follow-up. Kaplan-Meier curves and log-rank tests of the time-to-event data were used to assess differences in survival. RESULTS: In total, 296 consecutive patients with atrial fibrillation who survived an ICH were included in this study. Our analysis demonstrated that antithrombotic therapy was associated with reduced mortality up to a 4-year duration of follow-up (OR, 0.49, 95 % CI 0.30-0.81). Similar results were obtained from the propensity-matched analysis (OR, 0.58, 95 % CI 0.34-0.98). Subgroup analysis showed that compared with usual care, direct oral anticoagulant (DOAC) with or without antiplatelet was associated with a lower risk of long-term mortality (OR, 0.34, 95 % CI 0.17-0.69). In addition, our analysis observed a significant interaction between cardiac insufficiency and treatment effect (P = 0.04). CONCLUSIONS: In patients with atrial fibrillation who have a history of ICH, administration of antithrombotic therapy, especially DOAC, was associated with lower mortality. Future randomized trials are warranted to test the positive net clinical benefit of DOAC therapy.

Trends in prior antithrombotic medication and risk of in-hospital mortality after spontaneous intracerebral hemorrhage: the J-ICH registry.

Spontaneous intracerebral hemorrhage (SICH) remains a devastating form of stroke. Prior use of antiplatelets or warfarin before SICH is associated with poor outcomes, but the effects of direct oral anticoagulants (DOACs) remain unclear. This study aimed to clarify trends in prior antithrombotic use and to assess the associations between prior use of antithrombotics and in-hospital mortality using a multicenter prospective registry in Japan. In total, 1085 patients were analyzed. Prior antithrombotic medication included antiplatelets in 14.2%, oral anticoagulants in 8.1%, and both in 1.8%. Prior warfarin use was significantly associated with in-hospital mortality (odds ratio [OR] 5.50, 95% confidence interval [CI] 1.30-23.26, P < 0.05) compared to no prior antithrombotic use. No such association was evident between prior DOAC use and no prior antithrombotic use (OR 1.34, 95% CI 0.44-4.05, P = 0.606). Concomitant use of antiplatelets and warfarin further increased the in-hospital mortality rate (37.5%) compared to warfarin alone (17.2%), but no such association was found for antiplatelets plus DOACs (8.3%) compared to DOACs alone (11.9%). Prior use of warfarin remains an independent risk factor for in-hospital mortality after SICH in the era of DOACs. Further strategies are warranted to reduce SICH among patients receiving oral anticoagulants and to prevent serious outcomes.

Predictors of 30-Day Mortality for Surgically Treated Patients with Spontaneous Supratentorial Intracerebral Hemorrhage and Validation of the Surgical Swedish Intracerebral Hemorrhage Score: A Retrospective Single-Center Analysis of 136 Cases.

OBJECTIVE: We aimed to identify independent risk factors of 30-day mortality in patients with surgically treated spontaneous supratentorial intracerebral hemorrhage (ICH), validate the Surgical Swedish ICH (SwICH) score within Polish healthcare system, and compare the SwICH score to the ICH score. METHODS: We carried out a single-center retrospective analysis of the medical data juxtaposed with computed tomography scans of 136 ICH patients treated surgically between 2008 and 2022. Statistical analysis was performed using the same characteristics as in the SwICH score and the ICH score. Backward stepwise logistic regression with both 5-fold crossvalidation and 1000× bootstrap procedure was used to create new scoring system. Finally predictive potential of these scales were compared. RESULTS: The most important predictors of 30-day mortality were: ICH volume (P < 0.01), Glasgow Coma Scale at admission (P < 0.01), anticoagulant status (P = 0.03), and age (P < 0.01). The SwICH score appears to have a better predictive potential than the ICH score, although this did not reach statistical significance [area under the curve {AUC}: 0.789 (95% confidence interval {CI}: 0.715-0.863) vs. AUC: 0.757 (95% CI: 0.677-0.837)]. Moreover, based on the analyzed characteristics, we developed our score (encompassing: age, ICH volume, anticoagulants status, Glasgow Coma Scale at admission), [AUC of 0.872 (95% CI: 0.815-0.929)]. This score was significantly better than previous ones. CONCLUSIONS: Differences in health care systems seem to affect the accuracy of prognostic scales for patients with ICH, including possible differences in indications for surgery and postoperative care. Thus, it is important to validate assessment tools before they can be applied in a new setting and develop population-specific scores. This may improve the effectiveness of risk stratification in patients with ICH.

Trial of Early Minimally Invasive Removal of Intracerebral Hemorrhage.

BACKGROUND: Trials of surgical evacuation of supratentorial intracerebral hemorrhages have generally shown no functional benefit. Whether early minimally invasive surgical removal would result in better outcomes than medical management is not known. METHODS: In this multicenter, randomized trial involving patients with an acute intracerebral hemorrhage, we assessed surgical removal of the hematoma as compared with medical management. Patients who had a lobar or anterior basal ganglia hemorrhage with a hematoma volume of 30 to 80 ml were assigned, in a 1:1 ratio, within 24 hours after the time that they were last known to be well, to minimally invasive surgical removal of the hematoma plus guideline-based medical management (surgery group) or to guideline-based medical management alone (control group). The primary efficacy end point was the mean score on the utility-weighted modified Rankin scale (range, 0 to 1, with higher scores indicating better outcomes, according to patients' assessment) at 180 days, with a prespecified threshold for posterior probability of superiority of 0.975 or higher. The trial included rules for adaptation of enrollment criteria on the basis of hemorrhage location. A primary safety end point was death within 30 days after enrollment. RESULTS: A total of 300 patients were enrolled, of whom 30.7% had anterior basal ganglia hemorrhages and 69.3% had lobar hemorrhages. After 175 patients had been enrolled, an adaptation rule was triggered, and only persons with lobar hemorrhages were enrolled. The mean score on the utility-weighted modified Rankin scale at 180 days was 0.458 in the surgery group and 0.374 in the control group (difference, 0.084; 95% Bayesian credible interval, 0.005 to 0.163; posterior probability of superiority of surgery, 0.981). The mean between-group difference was 0.127 (95% Bayesian credible interval, 0.035 to 0.219) among patients with lobar hemorrhages and -0.013 (95% Bayesian credible interval, -0.147 to 0.116) among those with anterior basal ganglia hemorrhages. The percentage of patients who had died by 30 days was 9.3% in the surgery group and 18.0% in the control group. Five patients (3.3%) in the surgery group had postoperative rebleeding and neurologic deterioration. CONCLUSIONS: Among patients in whom surgery could be performed within 24 hours after an acute intracerebral hemorrhage, minimally invasive hematoma evacuation resulted in better functional outcomes at 180 days than those with guideline-based medical management. The effect of surgery appeared to be attributable to intervention for lobar hemorrhages. (Funded by Nico; ENRICH ClinicalTrials.gov number, NCT02880878.).

Reduced racial disparities among newborns with intraventricular hemorrhage.

INTRODUCTION: Intraventricular hemorrhage (IVH) can ensue permanent neurologic dysfunction, morbidity, and mortality. While previous reports have identified disparities based on patient gender or weight, no prior study has assessed how race may influence in neonatal or infantile IVH patients. The aim of this study was to investigate the impact of race on adverse event (AE) rates, length of stay (LOS), and total cost of admission among newborns with IVH. METHODS: Using the 2016-2019 National Inpatient Sample database, newborns diagnosed with IVH were identified using ICD-10-CM codes. Patients were stratified based on race. Patient characteristics and inpatient outcomes were assessed. Multivariate logistic regression analyses were used to identify the impact of race on extended LOS and exorbitant cost. RESULTS: Of 1435 patients, 650 were White (45.3%), 270 African American (AA) (18.8%), 300 Hispanic (20.9%), and 215 Other (15.0%). A higher percentage of AA and Other patients than Hispanic and White patients were < 28 days old (p = 0.008). Each of the cohorts had largely similar presenting comorbidities and symptoms, although AA patients did have significantly higher rates of NEC (p < 0.001). There were no observed differences in rates of AEs, rates of mortality, mean LOS, or mean total cost of admission. Similarly, on multivariate analysis, no race was identified as a significant independent predictor of extended LOS or exorbitant cost. CONCLUSIONS: Our study found that in newborns with IVH, race is not associated with proxies of poor healthcare outcomes like prolonged LOS or excessive cost. Further studies are needed to validate these findings.

Risk factors for unfavorable outcome after spontaneous intracerebral hemorrhage in elderly patients.

BACKGROUND: Spontaneous intracerebral hemorrhage (SICH) of the elderly is a devastating form of stroke with a high morbidity and economic burden. There is still a limited understanding of the risk factors for an unfavorable outcome where a surgical therapy may be less meaningful. Thus, the aim of this study is to identify factors associated with unfavorable outcome and time to death in surgically treated elderly patients with SICH. METHODS: We performed a single-center retrospective study of 70 patients (age > 60 years) with SICH operated between 2008 and 2020. Functional outcome was assessed by modified Rankin Scale. Various clinical and neuroradiological variables including type of neurosurgical treatment, anatomical location of hemorrhage, volumetry and distribution of hemorrhage were assessed. Univariate and multivariate logistic regression models were performed. Length of stay (LOS) and hospital costs are presented. RESULTS: The overall mortality (mean follow-up time of 22 months) in this study was 32/70 patients (45.71%), 30-days mortality was 8/70 (11.42%), and 12-months mortality was 22/70 (31.43%). Average LOS was 73.5 days with a median of 58, 766 € estimated in hospital costs per patient. Multivariate analysis for 12-months mortality was significant for intraventricular hemorrhage (IVH) (p = 0.007, HR = 1.021, 95% CI = 1.006 - 1.037). ROC analysis for 12-months mortality for IVH volume >= 7 cm3 presented an are under the curve of 0.658. CONCLUSIONS: We identified IVH volume > 7 cm3 as an independent prognostic risk factor for mortality in elderly patients after SICH. This may help clinicians in decision-making for this critical and growing subgroup of patients.

Utilizing the International Normalized Ratio-Platelet Index for Predicting Hospital Outcomes After Spontaneous Supratentorial Intracerebral Hemorrhage.

OBJECTIVE: Spontaneous intracerebral hemorrhage (ICH) poses a public health issue due to its elevated mortality rates. The International Normalized Ratio-platelet index (INR-Plt index) has recently been recognized as a predictive factor for liver disease progression. The potential of applying the INR-Plt index in forecasting ICH prognosis presents an intriguing subject. This study endeavors to examine the correlation between the INR-Plt index and hospital outcomes in patients with spontaneous supratentorial ICH. METHODS: A retrospective examination of 283 adult ICH patients was undertaken. The INR-Plt index was computed using the formula: [INR/platelet counts (1000/µL)] × 100. The clinical outcomes evaluated consisted of mortality rates and the Modified Rankin Scale (mRS) at discharge. An unfavorable outcome was defined as an mRS score from 4 to 6. RESULTS: The study found a significant correlation between the INR-Plt index and hospital mortality (odds ratio: 4.31, 95% CI: 1.07-17.31, P = 0.04). There was a 43% rise in mortality risk for every 0.1 unit increase in the INR-Plt index. Kaplan-Meier survival curves illustrated a considerably lower survival rate at discharge for patients with an INR-Plt index >0.8 (log-rank test: P = 0.047). Regarding unfavorable outcomes, the INR-Plt index was not a significant factor according to logistic regression analyses. CONCLUSIONS: The INR-Plt index is a predictor of hospital mortality in patients with spontaneous supratentorial ICH. A higher INR-Plt index value is associated with an increased risk of mortality, underlining the potential usefulness of this composite index in guiding clinical decision-making and enabling risk stratification.

Functional outcome improvement from 3 to 12 months after intracerebral hemorrhage.

INTRODUCTION: Most intracerebral hemorrhage (ICH) trials assessed outcome at 3 months but the recovery trajectory of ICH survivors may continue up to 1 year after the index event. We aimed to describe the predictors of functional outcome improvement from 3 to 12 months after ICH. MATERIALS AND METHODS: Retrospective analysis of patients admitted to six European Stroke Centers for supratentorial ICH. Functional outcome was measured with the modified Rankin Scale (mRS) at 3 and 12 months. Predictors of functional outcome improvement were explored with binary logistic regression. RESULTS: We included 703 patients, of whom 245 (34.9%) died within 3 months. Among survivors, 131 (28.6%) had an mRS improvement, 78 (17.0%) had a worse mRS and 249 (54.4%) had a stable functional status at 12 months. Older age and the presence of baseline disability (defined as pre-stroke mRS > 1), were associated with lower odds of functional outcome improvement (Odds Ratio (OR) 0.98 per year increase, 95% Confidence Interval (CI) 0.96-1.00, p = 0.017 and OR 0.45, 95% CI 0.25-0.81, p = 0.008 respectively). Conversely, deep ICH location increased the probability of long term mRS improvement (OR 1.67, 95% CI, 1.07-2.61, p = 0.023). Patients with mild-moderate disability at 3 months (mRS 2-3) had the highest odds of improvement at 12 months (OR 8.76, 95% CI 3.68-20.86, p < 0.001). DISCUSSION AND CONCLUSION: Long term recovery is common after ICH and associated with age, baseline functional status, mRS at 3 months and hematoma location. Our findings might inform future trials and improve long-term prognostication in clinical practice.

Ten-year national trends in in-hospital mortality and functional outcomes after intracerebral hemorrhage by age in Japan: J-ASPECT study.

INTRODUCTION: National-level data on trends in the prognosis of age-stratified patients with intracerebral hemorrhage (ICH) are lacking. This study aimed to assess time trends in in-hospital mortality and functional outcomes of ICH patients by sex and age, and to explore factors associated with changes in in-hospital mortality trend. PATIENTS AND METHODS: Using the largest nationwide, J-ASPECT stroke database in Japan, this serial cross-sectional study included ICH patients aged ⩾18 years who were hospitalized for non-traumatic ICH from April 2010 to March 2020. We examined trends in in-hospital mortality and functional outcomes using the modified Rankin Scale at discharge, as well as differences in in-hospital mortality change between age groups. RESULTS: Among 262,399 ICH patients from 934 hospitals, crude in-hospital mortality showed a significant decreasing time trend (from 19.5% to 16.7%), and this trend was consistent across sex and age groups. In addition, differences in in-hospital mortality change over the 10-year study period were significant between male patients aged ⩾75 years and those aged ⩽64 years (-3.9% [95% confidence interval, -5.4 to -2.4] for 75-84 years; -4.1% [-6.3 to -1.9] for ⩾85 years). On the other hand, the proportion of dependent patients (mRS 3-5) at discharge increased from 52.0% to 54.9% over the 10-year study period. CONCLUSION: The in-hospital mortality of ICH patients improved, whereas the proportion of patients with dependent functional outcome at discharge increased, over the 10-year study period. Elucidating the mechanism underlying differences in in-hospital mortality reduction in men may provide insights into effective interventions in the future.

Impact of concomitant necrotizing enterocolitis on mortality in very low birth weight infants with intraventricular hemorrhage.

OBJECTIVE: To evaluate the impact of necrotizing enterocolitis (NEC) on mortality in very low birth weight (VLBW) infants with intraventricular hemorrhage (IVH). STUDY DESIGN: Data were collected on VLBW infants born 2014-2018 at Vermont Oxford Network (VON) centers. NEC and IVH were categorized by severity. Adjusted risk ratios (ARR) for in-hospital mortality were calculated. RESULTS: This study included 187 187 VLBW infants. Both medical and surgical NEC increased mortality risk compared to those without NEC. Stratification by IVH severity modified this effect (no IVH: ARR 3.04 (95%CI 2.74-3.38) for medical NEC and 4.17 (3.84-4.52) for surgical NEC; mild IVH: ARR 2.14 (1.88-2.44) for medical NEC and 2.49 (2.24-2.78) for surgical NEC; severe IVH: ARR 1.14 (1.03-1.26) for medical NEC and 1.10 (1.02-1.18) for surgical NEC). CONCLUSION: The relative impact of NEC on mortality decreased as IVH severity increased. Given the frequent coexistence of NEC and IVH, these data inform multidisciplinary management of these complex patients.

Efficacy and safety of activated prothrombin complex concentrate for the reversal of vitamin K antagonist major bleeding.

Data on the use of activated prothrombin complex concentrate (aPCC) for the management of warfarin associated major bleeding is sparse. The objective of the study was to assess the achievement of effective clinical hemostasis using aPCC in patients presenting with major bleeding while on warfarin. We also assessed the safety of the drug. This retrospective study was conducted at a tertiary care teaching center in the USA where patients with major bleeding while receiving warfarin, and received aPCC were included. Efficacy of aPCC in achieving effective hemostasis was assessed according to the International Society of Thrombosis and Hemostasis Scientific and Standardization Subcommittee criteria. Efficacy was also assessed by achieving INR < 1.5 after treatment. The primary safety endpoint was the occurrence of any thromboembolic complications. A total of 67 patients were included in the study. The most common site for bleeding was intracerebral hemorrhage (n = 37, 55.2%), followed by gastrointestinal bleed (n = 26, 38.8%). Clinical hemostasis was achieved in 46 (68.7%) patients and of the 21 (31.3%) patients who did not achieve clinical hemostasis, 16 died. Thirty nine (58.2%) patients achieved INR < 1.5. Five (7.5%) patients developed thromboembolic complications. This study suggests that the use of aPCCs is effective in achieving effective hemostasis in patients on warfarin presenting with major bleeding.

Development and validation of a 30-day death nomogram in patients with spontaneous cerebral hemorrhage: a retrospective cohort study.

The purpose of this study was to establish and validate a nomogram to estimate the 30-day probability of death in patients with spontaneous cerebral hemorrhage. From January 2015 to December 2017, a cohort of 450 patients with clinically diagnosed cerebral hemorrhage was collected for model development. The minimum absolute contraction and the selection operator (lasso) regression model were used to select the strongest prediction of patients with cerebral hemorrhage. Discrimination and calibration were used to evaluate the performance of the resulting nomogram. After internal validation, the nomogram was further assessed in a different cohort containing 148 consecutive subjects examined between January 2018 and December 2018. The nomogram included five predictors from the lasso regression analysis, including: Glasgow coma scale (GCS), hematoma location, hematoma volume, white blood cells, and D-dimer. Internal verification showed that the model had good discrimination, (the area under the curve is 0.955), and good calibration [unreliability (U) statistic, p = 0.739]. The nomogram still showed good discrimination (area under the curve = 0.888) and good calibration [U statistic, p = 0.926] in the verification cohort data. Decision curve analysis showed that the prediction nomogram was clinically useful. The current study delineates a predictive nomogram combining clinical and imaging features, which can help identify patients who may die of cerebral hemorrhage.

C-Reaction Protein and the Severity of Intracerebral Hemorrhage: A Study from Chinese Stroke Center Alliance.

BACKGROUND: Intracerebral hemorrhage (ICH) has a high mortality and morbidity in the world. C-Reaction Protein (CRP) has been demonstrated to be an independent risk factor and could predict the severity and outcome of ischemic stroke. In our study, we aimed to find out the relationship between CRP levels and the severity and outcome of patients with ICH. METHODS: This study comes from the Chinese Stroke Center Alliance (CSCA). Patients' basic characteristics and laboratory examination results, including the concentration of CRP were taken from August 2015 to July 2019. Chi-square test and Logistic regression were used to analyze the relationship between different CRP levels and clinical outcome. RESULTS: A total of 9589 patients with acute ICH were enrolled in our study. In the logistic regression analysis, we found out that high CRP level is an independent risk factor for the prevalence of severe ICH and in-hospital death. After adjusting sex, age and other relevant stroke risk factors, the difference still exists (Severe ICH: odd ratio (OR) (95% confidence interval (CI) = 1.14 (1.04-1.26), P = 0.0076 for CRP between 3-10mg/l group and 1.64 (1.46-1.84), P<0.0001 for CRP>10mg/l group. In-hospital death: OR(95%CI)= 2.03(1.39-2.95), P=0.0002 for CRP>10mg/l group). CONCLUSIONS: High CRP level was independently associated with poorer clinical outcome and higher in-hospital death in patients with ICH.