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.

Association between elevated fibrosis-4 index of liver fibrosis and risk of hemorrhagic stroke.

BACKGROUND: Cirrhosis is associated with an increased risk of hemorrhagic stroke. Liver fibrosis, typically a silent condition, is antecedent to cirrhosis. The objective of this study was to test the hypothesis that elevated Fibrosis-4 (FIB-4) index, indicating a high probability of liver fibrosis, is associated with an increased risk of hemorrhagic stroke. METHODS: We performed a cohort analysis of the prospective United Kingdom Biobank cohort study. Participants 40-69 years old were enrolled between 2007 and 2010 and had available follow-up data until March 1, 2018. We excluded participants with prevalent hemorrhagic stroke or thrombocytopenia. High probability of liver fibrosis was defined as having a value >2.67 of the validated FIB-4 index. The primary outcome was hemorrhagic stroke (intracerebral or subarachnoid hemorrhage), defined based on hospitalization and death registry data. Secondary outcomes were intracerebral and subarachnoid hemorrhage, separately. We used Cox proportional hazards models to evaluate the association of FIB-4 index >2.67 with hemorrhagic stroke while adjusting for potential confounders including hypertension, alcohol use, and antithrombotic use. RESULTS: Among 452,994 participants (mean age, 57 years; 54% women), approximately 2% had FIB-4 index >2.67, and 1241 developed hemorrhagic stroke. In adjusted models, FIB-4 index >2.67 was associated with an increased risk of hemorrhagic stroke (HR, 2.0; 95% CI, 1.6-2.6). Results were similar for intracerebral hemorrhage (HR, 2.0; 95% CI, 1.5-2.7) and subarachnoid hemorrhage (HR, 2.2; 95% CI, 1.5-3.5) individually. CONCLUSIONS: Elevated FIB-4 index was associated with an increased risk of hemorrhagic stroke.

Association Between Hematoma Volume and Risk of Subsequent Ischemic Stroke: A MISTIE III and ATACH-2 Analysis.

BACKGROUND: Nontraumatic intracerebral hemorrhage (ICH) is independently associated with a long-term increased risk of major arterial ischemic events. While the relationship between ICH location and ischemic risk has been studied, whether hematoma volume influences this risk is poorly understood. METHODS: We pooled individual patient data from the MISTIE III (Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation Phase 3) and the ATACH-2 (Antihypertensive Treatment of Acute Cerebral Hemorrhage-2) trials. The exposure was hematoma volume, treated as a continuous measure in the primary analysis, and dichotomized by the median in the secondary analyses. The outcome was a symptomatic, clinically overt ischemic stroke, adjudicated centrally within each trial. We evaluated the association between hematoma volume and the risk of an ischemic stroke using Cox regression analyses after adjustment for demographics, vascular comorbidities, and ICH characteristics. RESULTS: Of 1470 patients with ICH, the mean age was 61.7 (SD, 12.8) years, and 574 (38.3%) were female. The median hematoma volume was 17.3 mL (interquartile range, 7.2-35.7). During a median follow-up of 107 days (interquartile range, 91-140), a total of 30 ischemic strokes occurred, of which 22 were in patients with a median ICH volume of ≥17.3 mL and a cumulative incidence of 4.6% (95% CI, 3.1-7.1). Among patients with a median ICH volume <17.3 mL, there were 8 ischemic strokes with a cumulative incidence of 3.1% (95% CI, 1.7-6.0). In primary analyses using adjusted Cox regression models, ICH volume was associated with an increased risk of ischemic stroke (hazard ratio, 1.02 per mL increase [95% CI, 1.01-1.04]). In secondary analyses, ICH volume of ≥17.3 mL was associated with an increased risk of ischemic stroke (hazard ratio, 2.5 [95% CI, 1.1-7.2]), compared with those with an ICH volume <17.3 mL. CONCLUSIONS: In a heterogeneous cohort of patients with ICH, initial hematoma volume was associated with a heightened short-term risk of ischemic stroke.

HY5: a key regulator for light-mediated nutrient uptake and utilization by plants.

ELONGATED HYPOCOTYL 5 (HY5), a bZIP-type transcription factor, is a master regulator of light-mediated responses. ELONGATED HYPOCOTYL 5 binds to the promoter of c. 3000 genes, thereby regulating various physiological and biological processes, including photomorphogenesis, flavonoid biosynthesis, root development, response to abiotic stress and nutrient homeostasis. In recent decades, it has become clear that light signaling plays a crucial role in promoting nutrient uptake and assimilation. Recent studies have revealed the molecular mechanisms underlying such encouraging effects and the crucial function of the transcription factor HY5, whose activity is regulated by many photoreceptors. The discovery that HY5 directly activates the expression of genes involved in nutrient uptake and utilization, including several nitrogen, iron, sulphur, phosphorus and copper uptake and assimilation-related genes, enhances our understanding of how light signaling regulates uptake and utilisation of multiple nutrients in plants. Here, we review recent advances in the role of HY5 in light-dependent nutrient uptake and utilization.

Association Between Neutrophil-Lymphocyte Ratio and 30-Day Infection and Thrombotic Outcomes After Intraventricular Hemorrhage: A CLEAR III Analysis.

BACKGROUND: Serum neutrophil-lymphocyte ratio (NLR) is a surrogate marker for the inflammatory response after intracerebral hemorrhage (ICH) and is associated with perihematomal edema and long-term functional outcomes. Whether NLR is associated with short-term ICH complications is poorly understood. We hypothesized that NLR is associated with 30-day infection and thrombotic events after ICH. METHODS: We performed a post hoc exploratory analysis of the Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage III trial. The study exposure was the serum NLR obtained at baseline and on days 3 and 5. The coprimary outcomes, ascertained at 30 days, were any infection and a thrombotic event, defined as composite of cerebral infarction, myocardial infarction, or venous thromboembolism; both infection and thrombotic event were determined through adjudicated adverse event reporting. Binary logistic regression was used to study the relationship between NLR and outcomes, after adjustment for demographics, ICH severity and location, and treatment randomization. RESULTS: Among the 500 patients enrolled in the Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage III trial, we included 303 (60.6%) without missing data on differential white blood cell counts at baseline. There were no differences in demographics, comorbidities, or ICH severity between patients with and without data on NLR. In adjusted logistic regression models, NLR ascertained at baseline (odds ratio [OR] 1.03; 95% confidence interval [CI] 1.01-1.07, p = 0.03) and NLR ascertained at day 3 were associated with infection (OR 1.15; 95% CI 1.05-1.20, p = 0.001) but not with thrombotic events. Conversely, NLR at day 5 was associated with thrombotic events (OR 1.07, 95% CI 1.01-1.13, p = 0.03) but not with infection (OR 1.13; 95% CI 0.76-1.70, p = 0.56). NLR at baseline was not associated with either outcome. CONCLUSIONS: Serum NLR ascertained at baseline and on day 3 after randomization was associated with 30-day infection, whereas NLR obtained on day 5 was associated with thrombotic events after ICH, suggesting that NLR could be a potential early biomarker for ICH-related complications.

Catheter Tract Hemorrhages and Intracerebral Hemorrhage Outcomes in the Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Trial.

BACKGROUND AND OBJECTIVES: Factors associated with external ventricular catheter tract hemorrhage (CTH) are well studied; whether CTH adversely influence outcomes after intracerebral hemorrhage (sICH), however, is poorly understood. We therefore sought to evaluate the association between CTH and sICH outcomes. METHODS: We performed a post hoc analysis of the Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage trial. The exposure was CTH and evaluated on serial computed tomography scans between admission and randomization (approximately 72 hours). The primary outcomes were a composite of death or major disability (modified Rankin Score >3) and mortality alone, both assessed at 6 months. Secondary outcomes were functional outcomes at 30 days, permanent cerebrospinal fluid (CSF) shunt placement, any infection, and ventriculitis. We performed logistic regression adjusted for demographics, comorbidities, sICH characteristics, and treatment assignment, for all analyses. RESULTS: Of the 500 patients included, the mean age was 59 (SD, ±11) years and 222 (44%) were female. CTH occurred in 112 (22.4%) patients and was more common in minority patients, those on prior antiplatelet therapy, and patients who had more than 1 external ventricular drain placed. The end of treatment intraventricular hemorrhage volume was higher among patients with CTH (11.7 vs 7.9 mL, P = .01), but there were no differences in other sICH characteristics or the total duration of external ventricular drain. In multivariable regression models, CTH was not associated with death or major disability (odds ratio, 0.7; 95% CI: 0.4-1.2) or death alone (odds ratio, 0.8; 95% CI, 0.5-1.4). There were no relationships between CTH and secondary outcomes including 30-day functional outcomes, permanent CSF shunt placement, any infection, or ventriculitis. CONCLUSION: Among patients with sICH and large intraventricular hemorrhage, CTH was not associated with poor sICH outcomes, permanent CSF shunt placement, or infections. A more detailed cognitive evaluation is needed to inform about the role of CTH in sICH prognosis.

Cerebral Amyloid Angiopathy and Risk of Isolated Nontraumatic Subdural Hemorrhage.

Importance: Cerebral amyloid angiopathy (CAA) is a common cause of spontaneous intracerebral hemorrhage in older patients. Although other types of intracranial hemorrhage can occur in conjunction with CAA-related intracerebral hemorrhage, the association between CAA and other subtypes of intracranial hemorrhage, particularly in the absence of intracerebral hemorrhage, remains poorly understood. Objective: To determine whether CAA is an independent risk factor for isolated nontraumatic subdural hemorrhage (SDH). Design, Setting, and Participants: A population-based cohort study was performed using a 2-stage analysis of prospectively collected data in the UK Biobank cohort (discovery phase, 2006-2022) and the All of Us Research Program cohort (replication phase, 2018-2022). Participants included those who contributed at least 1 year of data while they were older than 50 years, in accordance with the diagnostic criteria for CAA. Participants with prevalent intracranial hemorrhage were excluded. Data were analyzed from October 2022 to October 2023. Exposure: A diagnosis of CAA, identified using the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnosis code. Main Outcomes and Measures: The outcome was an isolated nontraumatic SDH, identified using ICD-10-CM codes. Two identical analyses were performed separately in the 2 cohorts. First, the risk of SDH in patients with and without CAA was assessed using Cox proportional hazards models, adjusting for demographic characteristics, cardiovascular comorbidities, and antithrombotic medication use. Second, multivariable logistic regression was used to study the association between CAA and SDH. Results: The final analytical sample comprised 487 223 of the total 502 480 individuals in the UK Biobank cohort and 158 008 of the total 372 082 individuals in the All of Us cohort. Among the 487 223 participants in the discovery phase of the UK Biobank, the mean (SD) age was 56.5 (8.1) years, and 264 195 (54.2%) were female. There were 649 cases of incident SDH. Of the 126 participants diagnosed with CAA, 3 (2.4%) developed SDH. In adjusted Cox regression analyses, participants with CAA had an increased risk of having an SDH compared with those without CAA (hazard ratio [HR], 8.0; 95% CI, 2.6-24.8). Multivariable logistic regression analysis yielded higher odds of SDH among participants with CAA (odds ratio [OR], 7.6; 95% CI, 1.8-20.4). Among the 158 008 participants in the All of Us cohort, the mean (SD) age was 63.0 (9.5) years, and 89 639 (56.7%) were female. The findings were replicated in All of Us, in which 52 participants had CAA and 320 had an SDH. All of Us participants with CAA had an increased risk of having an SDH compared with those without CAA (HR, 4.9; 95% CI, 1.2-19.8). In adjusted multivariable logistic regression analysis, CAA was associated with higher odds of SDH (OR, 5.2; 95% CI, 0.8-17.6). Conclusions and Relevance: In 2 large, heterogeneous cohorts, CAA was associated with increased risk of SDH. These findings suggest that CAA may be a novel risk factor for isolated nontraumatic SDH.

Concentration of clarified pool by single-pass tangential flow filtration to improve productivity of protein A capture step: Impact of clarification strategies.

Protein A capture chromatography remains a high-cost and relatively low-productivity step for downstream processing of monoclonal antibodies. As bioprocessing transitions toward intensified processes, maximizing the efficiency of individual steps is key to achieving economic targets. This study was performed to assess the impact of inline concentration of clarified cell culture fluid (CCF), using single-pass tangential flow filtration, on protein A chromatography purification productivity. CCF with varying levels of impurities and turbidity were obtained dependent upon the clarification method. These CCFs were concentrated and processed over a protein A capture step. Productivity increases of 1.8- to 2.6-fold were achieved as compared to a protein A capture step with no CCF concentration. Achieving such targeted improvements requires careful consideration of the multiple components in the clarification strategy before implementation.

Overexpression of HMGB1 in hepatocytes accelerates PTEN inactivation-induced liver cancer.

BACKGROUND: Liver cancer is increasing due to the rise in metabolic dysfunction-associated steatohepatitis (MASH). High-mobility group box-1 (HMGB1) is involved in the pathogenesis of chronic liver disease, but its role in MASH-associated liver cancer is unknown. We hypothesized that an increase in hepatocyte-derived HMGB1 in a mouse model of inactivation of PTEN that causes MASH could promote MASH-induced tumorigenesis. METHODS: We analyzed publicly available transcriptomics datasets, and to explore the effect of overexpressing HMGB1 in cancer progression, we injected 1.5-month-old Pten∆Hep mice with adeno-associated virus serotype-8 (AAV8) vectors to overexpress HMGB1-EGFP or EGFP, and sacrificed them at 3, 9 and 11 months of age. RESULTS: We found that HMGB1 mRNA increases in human MASH and MASH-induced hepatocellular carcinoma (MASH-HCC) compared to healthy livers. Male and female Pten∆Hep mice overexpressing HMGB1 showed accelerated liver tumor development at 9 and 11 months, respectively, with increased tumor size and volume, compared to control Pten∆Hep mice. Moreover, Pten∆Hep mice overexpressing HMGB1, had increased incidence of mixed HCC-intrahepatic cholangiocarcinoma (iCCA). All iCCAs were positive for nuclear YAP and SOX9. Male Pten∆Hep mice overexpressing HMGB1 showed increased cell proliferation and F4/80+ cells at 3 and 9 months. CONCLUSION: Overexpression of HMGB1 in hepatocytes accelerates liver tumorigenesis in Pten∆Hep mice, enhancing cell proliferation and F4/80+ cells to drive MASH-induced liver cancer.

Mechanistic Evaluation of Diffusion Weighted Hyperintense Lesions After Large Spontaneous Intracerebral Hemorrhage: A Subgroup Analysis of MISTIE III.

BACKGROUND: Ischemic lesions on diffusion weighted imaging (DWI) are common after acute spontaneous intracerebral hemorrhage (ICH) but are poorly understood for large ICH volumes (> 30 mL). We hypothesized that large blood pressure drops and effect modification by cerebral small vessel disease markers on magnetic resonance imaging (MRI) are associated with DWI lesions. METHODS: This was an exploratory analysis of participants in the Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation phase 3 trial with protocolized brain MRI scans within 7 days from ICH. Multivariable logistic regression analysis was performed to assess biologically relevant factors associated with DWI lesions, and relationships between DWI lesions and favorable ICH outcomes (modified Rankin Scale 0-3). RESULTS: Of 499 enrolled patients, 300 had MRI at median 7.5 days (interquartile range 7-8), and 178 (59%) had DWI lesions. The incidence of DWI lesions was higher in patients with systolic blood pressure (SBP) reduction ≥ 80 mm Hg in first 24 h (76%). In adjusted models, factors associated with DWI lesions were as follows: admission intraventricular hematoma volume (p = 0.03), decrease in SBP ≥ 80 mm Hg from admission to day 1 (p = 0.03), and moderate-to-severe white matter disease (p = 0.01). Patients with DWI lesions had higher odds of severe disability at 1 month (p = 0.04), 6 months (p = 0.036), and 12 months (p < 0.01). No evidence of effect modification by cerebral small vessel disease on blood pressure was found. CONCLUSIONS: In patients with large hypertensive ICH, white matter disease, intraventricular hemorrhage volume, and large reductions in SBP over the first 24 h were independently associated with DWI lesions. Further investigation of potential hemodynamic mechanisms of ischemic injury after large ICH is warranted.

SOD-GIF-FIT module controls plant organ size and iron uptake.

Plant organ growth is controlled by various internal and external cues. However, the underlying molecular mechanisms that coordinate plant organ growth and nutrient homeostasis remain largely unknown. Recently, Zheng et al. identified the key regulators SOD7 (suppressor of da1-1) and GRF-INTERACTING FACTOR1 (GIF1) that control organ size and iron uptake in arabidopsis (Arabidopsis thaliana).

Antithrombotic and Statin Prescription After Intracerebral Hemorrhage in the Get With The Guidelines-Stroke Registry.

BACKGROUND: Survivors of intracerebral hemorrhage (ICH) face an increased risk of ischemic cardiovascular events. Current ICH guidelines do not provide definitive recommendations regarding the use of antithrombotic and statin therapies. We, therefore, sought to study practice patterns and factors associated with the use of such medications after ICH. METHODS: This was a cross-sectional study of patients with ICH in the Get With The Guidelines-Stroke registry, between 2011 and 2021. Patients transferred to another hospital, those who died during hospitalization, and those with missing information on discharge medications were excluded. The study exposure was the proportion of patients who were prescribed antithrombotic or statin medications. We first ascertained the proportion of patients prescribed antithrombotic and lipid-lowering medications at discharge overall and across strata defined by pre-ICH use and history of previous ischemic vascular disease or atrial fibrillation. We then studied factors associated with the discharge prescription of these medications after ICH, using multiple logistic regressions. RESULTS: In the final cohort, 50 416 (10.4%) of 486 586 patients with ICH were prescribed antiplatelet medications, 173 322 (35.1%) of 493 491 patients with ICH were prescribed statins, and 27 085 (5.4%) of 486 585 patients with ICH were prescribed anticoagulation therapy at discharge. The proportion of patients with antiplatelet therapy was 16.6% with pre-ICH use and 15.6% in those with previous ischemic vascular disease. Statins were prescribed to 41.1% and 43.7% of patients on previous lipid-lowering therapy and ischemic vascular disease, respectively. Anticoagulation therapy was restarted in 11.1% of patients. In logistic regression analysis, factors associated with higher use of antithrombotic or statin therapies after ICH were younger age, male sex, pre-ICH medication use, previous ischemic vascular disease, atrial fibrillation, lower admission National Institutes of Health Stroke Scale, longer length of stay, and favorable discharge outcome. CONCLUSIONS: Few patients with ICH are prescribed antithrombotic or statin therapies at hospital discharge. Given the emerging association between ICH and future major cardiovascular events, trials examining the net benefit of antiplatelet and lipid-lowering therapy after ICH are warranted.

Cerebral small vessel disease modifies outcomes after minimally invasive surgery for intracerebral haemorrhage.

BACKGROUND: Minimally invasive surgery (MIS) for spontaneous supratentorial intracerebral haemorrhage (ICH) is controversial but may be beneficial if end-of-treatment (EOT) haematoma volume is reduced to ≤15 mL. We explored whether MRI findings of cerebral small vessel disease (CSVD) modify the effect of MIS on long-term outcomes. METHODS: Prespecified blinded subgroup analysis of 288 subjects with qualified imaging sequences from the phase 3 Minimally Invasive Surgery Plus Alteplase for Intracerebral Haemorrhage Evacuation (MISTIE) trial. We tested for heterogeneity in the effects of MIS and MIS+EOT volume ≤15 mL on the trial's primary outcome of good versus poor function at 1 year by the presence of single CSVD features and CSVD scores using multivariable models. RESULTS: Of 499 patients enrolled in MISTIE III, 288 patients had MRI, 149 (51.7%) randomised to MIS and 139 (48.3%) to standard medical care (SMC). Median (IQR) ICH volume was 42 (30-53) mL. In the full MRI cohort, there was no statistically significant heterogeneity in the effects of MIS versus SMC on 1-year outcomes by any specific CSVD feature or by CSVD scores (all Pinteraction >0.05). In 94 MIS patients with EOT ICH volume ≤15 mL, significant reduction in odds of poor outcome was found with cerebral amyloid angiopathy score <2 (OR, 0.14 (0.05-0.42); Pinteraction=0.006), absence of lacunes (OR, 0.37 (0.18-0.80); Pinteraction=0.02) and absence of severe white matter hyperintensities (WMHs) (OR, 0.22 (0.08-0.58); Pinteraction=0.03). CONCLUSIONS: Following successful haematoma reduction by MIS, we found significantly lower odds of poor functional outcome with lower total burden of CSVD in addition to absence of lacunes and severe WMHs. CSVD features may have utility for prognostication and patient selection in clinical trials of MIS.

Antiplatelet therapy and outcomes after aneurysmal subarachnoid hemorrhage: A systematic review and meta-analysis.

BACKGROUND: The efficacy of antiplatelet therapy (APT) after aneurysmal subarachnoid hemorrhage (aSAH) remains unclear. We performed a systematic review and meta-analysis to summarize the associations of APT use after aSAH with outcomes. METHODS: We searched published medical literature to identify cohort studies involving adults with aSAH. The exposure was APT use after aSAH. Outcome measures were good functional outcome (modified Rankin Score 0-2 or Glasgow Outcome Scale 4-5), delayed cerebral ischemia (infarcts on neuroimaging), and intracranial hemorrhage. After assessing study heterogeneity and publication bias, we performed a meta-analysis using random-effects models to assess the strength of association between APT and SAH outcomes. RESULTS: A total of 14 studies with 4228 aSAH patients were included. APT after aSAH was associated with good functional outcome (pooled relative risk, 1.08; 95% confidence interval, [CI], 1.02-1.15; I2 = 45%, p for heterogeneity = 0.04), but there was no relationship with delayed cerebral ischemia (pooled relative risk, 0.80; 95% confidence interval, [CI], 0.63-1.02; I2 = 61%, p for heterogeneity <0.01) or intracranial hemorrhage (pooled relative risk, 1.50; 95% confidence interval, [CI], 0.98-2.31; I2 = 0, p for heterogeneity =0.71). In additional analyses, APT resulted in good functional outcomes in endovascularly-treated patients. When stratified by type of medication, aspirin, clopidogrel, and ticlopidine were associated with good functional outcomes. CONCLUSIONS: APT after aSAH was associated with a modest improvement in functional outcome, but there was no relationship with delayed cerebral ischemia or intracranial hemorrhage.

Hypoglycemic activity of Syzygium cumini (L.) Skeels seed extracts: an approach to in vitro, in vivo, and in silico studies.

This research is carried out to explore the hypoglycemic activity of Syzygium cumini seed extracts by in vitro, in vivo, and in silico methods. For in vitro studies the α-amylase and α-glucosidase enzyme inhibition assays were employed. For in vivo studies 30 alloxan induced Wistar rats were used. They were orally administered with glibenclamide and low/high dose of the extracts and were monitored regularly for the change in blood glucose levels for about 28 days. The in silico molecular docking was conducted to evaluate the binding interaction of 1,2,3-Benzenetriol with human pancreatic α-amylase and α-glucosidase. It was found that all the extracts were able to inhibit the α-amylase and α-glucosidase enzymes. Among which the acetone extract showed greater inhibition with 72.52 ± 0.51% and 63.02 ± 0.73% for both the enzymes, respectively. There was significant (p < 0.05) reduction in blood glucose levels in the rats administered with glibenclamide and extracts. In silico docking results revealed that the compound 1,2,3-Benzenetriol exhibited the highest binding affinity for human pancreatic α-amylase with binding energy -7.7 kcal/mol. Thus suggesting the utilization of S. cumini seeds in the management of diabetes mellitus.Communicated by Ramaswamy H. Sarma.

Intensive Blood Pressure Reduction is Associated with Reduced Hematoma Growth in Fast Bleeding Intracerebral Hemorrhage.

OBJECTIVE: Patients with spontaneous intracerebral hemorrhage (ICH) at the highest risk of hematoma growth are those with the most potential to benefit from anti-expansion treatment. Large clinical trials have not definitively shown a clear benefit of blood pressure (BP) reduction. We aim to determine whether intensive blood pressure reduction could benefit patients with fast bleeding ICH. METHODS: An exploratory analysis of data from the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 (ATACH-2) randomized controlled trial was performed. In order to capture not just early bleeding (even if a small amount), but the rate of bleeding (ml/hour), we restricted the study to "Fast bleeding ICH," defined as an ICH volume/onset to computed tomography (CT) time >5 ml/hr. Hematoma growth, as defined as an increase of hematoma volume > 33% between baseline and 24 hours. RESULTS: A total of 940 patients were included (mean age = 62.1 years, 61.5% men), of whom 214 (22.8%) experienced hematoma expansion. Of these, 567 (60.3%) met the definition of "fast bleeding" with baseline ICH volume/time to presentation of at least 5 ml/hr. Intensive BP reduction was associated with a significantly lower rate of hematoma growth in fast bleeding patients (20.6% vs 31.0%, p = 0.005). In a subgroup of 266 (46.9%) fast-bleeding patients who received treatment within 2 hours after symptom onset, intensive BP lowering was associated with improved functional independence (odds ratio [OR] = 1.98, 95% confidence interval [CI] = 1.06-3.69, p = 0.031). INTERPRETATION: Our results suggest that early use of intensive BP reduction may reduce hematoma growth and improve outcome in fast bleeding patients. ANN NEUROL 2023.

Racial and Ethnic Differences in the Risk of Ischemic Stroke After Nontraumatic Intracerebral Hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) is associated with an increased risk of ischemic stroke. Whether there are racial and ethnic disparities in the risk of ischemic stroke after ICH is poorly understood. We therefore aimed to test the hypothesis that non-Hispanic Black and Hispanic ICH patients have a higher risk of ischemic stroke compared with non-Hispanic White ICH patients. METHODS: We performed a retrospective cohort study using the Healthcare Cost and Utilization Project (HCUP) on all hospitalizations at all nonfederal hospitals in Florida from 2005 to 2018 and New York from 2006 to 2016. Race and ethnicity were coded as a single variable in HCUP. We included patients with an ICH, and without a prior or concomitant diagnosis of ischemic stroke, ascertained using validated International Classification of Diseases-Clinical Modification-9 and 10 diagnosis codes. Using Cox proportional hazard models, we studied the relationship between race and risk of ischemic stroke starting from the time of discharge from ICH hospitalization, after adjustment of demographics and vascular comorbidities. RESULTS: We included 91 342 patients with ICH-62% non-Hispanic White, 18% non-Hispanic Black, and 12% Hispanic patients. Non-Hispanic Black and Hispanic patients were younger and had a higher prevalence of cardiovascular comorbidities; however, atrial fibrillation was more prevalent among non-Hispanic White patients. During a median follow-up period of 4.4 years (interquartile range, 1.5-8.1), an incident ischemic stroke occurred in 3377 (6%) non-Hispanic White, 1323 (8%) non-Hispanic Black, and 844 (8%) Hispanic patients. In adjusted Cox models, the risk of an ischemic stroke was significantly higher among non-Hispanic Black patients (hazard ratio, 1.6 [95% CI, 1.5-1.8]) and Hispanic patients (hazard ratio, 1.4 [95% CI, 1.3-1.5]), compared with non-Hispanic White patients. Similar results were obtained in sensitivity analyses when using death as a competing risk and after excluding patients with atrial fibrillation and valvular heart disease. CONCLUSIONS: In a large heterogeneous cohort of patients with ICH, we found that non-Hispanic Black and Hispanic patients had a significantly higher risk of ischemic stroke compared with non-Hispanic White patients.

Management of Stroke in Patients With Chronic Liver Disease: A Practical Review.

Chronic liver disease (CLD) is a highly prevalent condition. There is burgeoning recognition that there are many people with subclinical liver disease that may nonetheless be clinically significant. CLD has a variety of systemic aberrations relevant to stroke, including thrombocytopenia, coagulopathy, elevated liver enzymes, and altered drug metabolism. There is a growing body of literature on the intersection of CLD and stroke. Despite this, there have been few efforts to synthesize these data, and stroke guidelines provide scant guidance on this topic. To fill this gap, this multidisciplinary review provides a contemporary overview of CLD for the vascular neurologist while appraising data regarding the impact of CLD on stroke risk, mechanisms, and outcomes. Finally, the review addresses acute and chronic treatment considerations for patients with stroke-ischemic and hemorrhagic-and CLD.

Elucidation of intermolecular interactions between chlorogenic acid and glucose-6-phosphate translocase: A step towards chemically induced glycogen storage disease type 1b model.

Glucose-6-phosphate translocase enzyme, encoded by SLC37A4 gene, is a crucial enzyme involved in transporting glucose-6-phosphate into the endoplasmic reticulum. Inhibition of this enzyme can cause Von-Gierke's/glycogen storage disease sub-type 1b. The current study dealt to elucidate the intermolecular interactions to assess the inhibitory activity of Chlorogenic acid (CGA) against SLC37A4 was assessed by molecular docking and dynamic simulation. The alpha folded model of SLC37A4 and CGA 3D structure were optimized using CHARMM force field, using energy minimization protocol in the Discovery Studio software. Glucose-6-phosphate (G6P) and CGA molecular docking, Molecular dynamics (MD) simulation, analysis of binding free energy of G6P-SLC37A4 and CGA-SLC37A4 complexes was performed for 100 ns using GROMACS, followed by principal component analysis (PCA). The docking score of the CGA-SLC37A4 complex exhibited a higher docking score (- 8.2 kcal/mol) when compared to the G6P-SLC37A4 complex (- 6.5 kcal/mol), suggesting a stronger binding interaction between CGA and SLC37A4. Further, the MD simulation demonstrated a stable backbone and complex Root Mean Square Deviation (RMSD), the least RMS fluctuation, and stable active site residue interactions throughout the 100 ns production run. The CGA complex with SLC37A4 exhibits higher compactness and formed 8 hydrogen bonds to achieve stability. The binding free energy of the G6P-SLC37A4 and CGA-SLC37A4 complex was found to be - 12.73 and - 31.493 kcal/mol. Lys29 formed stable contact for both G6P (- 4.73 kJ/mol) and SLC37A4 (- 2.18 kJ/mol). This study imparts structural insights into the competitive inhibition of SLC37A4 by CGA. CGA shows potential as a candidate to induce manifestations of GSD1b by inhibiting glycogenolysis, and gluconeogenesis. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03661-5.