Intravenous Thrombolysis in Patients With Cervical Artery Dissection: A Secondary Analysis of the STOP-CAD Study.

OBJECTIVES: Cervical artery dissection (CeAD) accounts for 25% of ischemic strokes in young adults. This study evaluated the benefits and harms of intravenous thrombolysis (IVT) in patients presenting with spontaneous CeAD and acute ischemic stroke symptoms. METHODS: This analysis used data from the retrospective STOP-CAD study and included patients with spontaneous CeAD who presented within 1 day of acute ischemic stroke symptoms. Patients were dichotomized into those who received IVT and those managed without IVT. We assessed the association between IVT and 90-day functional independence (modified Rankin Scale scores 0-2) and the incidence of symptomatic intracranial hemorrhage (ICH, defined as ICH causing new or worsening neurologic symptoms within 72 hours after CeAD diagnosis). RESULTS: This study included 1,653 patients from the original STOP-CAD cohort of 4,023. The median age was 49 years, and 35.1% were women; 512 (31.0%) received IVT. IVT was associated with 90-day functional independence (adjusted odds ratio [aOR] = 1.67, 95% CI 1.23-2.28, p = 0.001), but not with symptomatic ICH (aOR = 1.52, 95% CI 0.79-2.92, p = 0.215). DISCUSSION: In patients with spontaneous CeAD and suspected ischemic stroke, IVT improved functional outcomes, without increasing symptomatic ICH risk. These findings support current guideline recommendations to consider thrombolysis for otherwise eligible patients with CeAD. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that IVT significantly increases the probability of 90-day functional independence in patients with CeAD.

Thrombolysis After Dabigatran Reversal for Acute Ischemic Stroke: A National Registry-Based Study and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Limited data exist on the safety of IV thrombolysis (IVT) for acute ischemic stroke (AIS) after dabigatran reversal with idarucizumab. We sought to evaluate the safety and efficacy of idarucizumab pretreatment in patients with AIS receiving IVT. METHODS: A national registry-based study evaluated the safety and efficacy of IVT in this specific subgroup. We also conducted a systematic review and meta-analysis of cohort studies and case series, aiming to document the pooled rates of (1) symptomatic intracranial hemorrhage (sICH), (2) any intracranial hemorrhage, (3) 3-month mortality, and (4) the proportion of excellent (modified Rankin Scale [mRS] scores 0-1) and (5) good (mRS scores 0-2) functional outcome at 3 months among patients with AIS, who received IVT after dabigatran reversal with idarucizumab. Moreover, we sought to compare these outcomes between IVT-treated patients after dabigatran reversal with idarucizumab and IVT-treated patients without dabigatran pretreatment. RESULTS: Thirteen cohorts including our nation-wide registry-based cohort and 1 case series comprising 553 patients with AIS (mean age: 75 years; male sex: 65%; median baseline NIH Stroke Scale score: 11 points) receiving idarucizumab before IVT were included in this meta-analysis. The pooled rate of sICH after IVT after idarucizumab administration was 4% (95% CI 1-9; I2 = 26%), while the pooled rates of any intracranial hemorrhage and 3-month mortality were 10% (95% CI 5-16; I2 = 24%) and 18% (95% CI 10-27; I2 = 0%), respectively. The pooled rates of excellent and good functional outcomes at 3 months were 56% (95% CI 27-83; I2 = 69%) and 70% (95% CI 57-81; I2 = 40%), respectively. The risk of sICH (risk ratio [RR] 1.86; 95% CI 0.91-3.80; I2 = 0%), any intracranial hemorrhage (RR 1.76; 95% CI 0.99-3.11; I2 = 8%), and 3-month mortality (RR 1.50; 95% CI 0.91-2.48; I2 = 0%) did not differ between patients with AIS receiving IVT with and without idarucizumab. Moreover, idarucizumab administration was associated with higher likelihood of achieving a 3-month good functional outcome (RR 1.35; 95% CI 1.11-1.65; I2 = 27%). DISCUSSION: IVT for AIS after dabigatran reversal with idarucizumab seems to be safe and effective in observational studies with limited number of patients. Randomized-controlled clinical trials are warranted to provide robust evidence on the safety and efficacy of IVT in this specific AIS subgroup.

Adjunctive Intravenous Argatroban or Eptifibatide for Ischemic Stroke.

BACKGROUND: Intravenous thrombolysis is a standard treatment of acute ischemic stroke. The efficacy and safety of combining intravenous thrombolysis with argatroban (an anticoagulant agent) or eptifibatide (an antiplatelet agent) are unclear. METHODS: We conducted a phase 3, three-group, adaptive, single-blind, randomized, controlled clinical trial at 57 sites in the United States. Patients with acute ischemic stroke who had received intravenous thrombolysis within 3 hours after symptom onset were assigned to receive intravenous argatroban, eptifibatide, or placebo within 75 minutes after the initiation of thrombolysis. The primary efficacy outcome, the utility-weighted 90-day modified Rankin scale score (range, 0 to 10, with higher scores reflecting better outcomes), was assessed by means of centralized adjudication. The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours after randomization. RESULTS: A total of 514 patients were assigned to receive argatroban (59 patients), eptifibatide (227 patients), or placebo (228 patients). All the patients received intravenous thrombolysis (70% received alteplase, and 30% received tenecteplase), and 225 patients (44%) underwent endovascular thrombectomy. At 90 days, the mean (±SD) utility-weighted modified Rankin scale scores were 5.2±3.7 with argatroban, 6.3±3.2 with eptifibatide, and 6.8±3.0 with placebo. The posterior probability that argatroban was better than placebo was 0.002 (posterior mean difference in utility-weighted modified Rankin scale score, -1.51±0.51) and that eptifibatide was better than placebo was 0.041 (posterior mean difference, -0.50±0.29). The incidence of symptomatic intracranial hemorrhage was similar in the three groups (4% with argatroban, 3% with eptifibatide, and 2% with placebo). Mortality at 90 days was higher in the argatroban group (24%) and the eptifibatide group (12%) than in the placebo group (8%). CONCLUSIONS: In patients with acute ischemic stroke treated with intravenous thrombolysis within 3 hours after symptom onset, adjunctive treatment with intravenous argatroban or eptifibatide did not reduce poststroke disability and was associated with increased mortality. (Funded by the National Institute of Neurological Disorders and Stroke; MOST ClinicalTrials.gov number, NCT03735979.).

Racial and ethnic differences in restarting antiplatelet therapy in patients with primary intracranial hemorrhage: a systematic review and meta-analysis.

BACKGROUND: There has long been clinical disagreement over the resumption of antiplatelet therapy in patients with primary intracranial hemorrhage (ICH). This meta-analysis aimed to systematically evaluate the efficacy and safety of restarting antiplatelet therapy after ICH among different races and ethnicities. METHODS: All relevant medical studies involving adults with antiplatelet-associated ICH published in PubMed, The Cochrane Library and Chinese National Knowledge Infrastructure from inception to March 2024 were sourced. Outcome measures were thromboembolic events (stroke and myocardial infarction) and recurrence of ICH. After assessing study heterogeneity and publication bias, we performed a meta-analysis using random-effects model to assess the strength of association between resumption of antiplatelet therapy and our outcomes.The review was not registered and the review protocol was not prepared. RESULTS: Thirty-five studies were included, with 9758 ICH patients. Subgroup analysis revealed that restarting antiplatelet therapy was associated with a significantly higher risk of recurrence or aggravation of cerebral hemorrhage in Asians[OR = 1.48, 95% CI (1.13-1.94), P = 0.004]; in Caucasians, on the contrary, reinitiation of antiplatelet therapy was not associated with a significantly higher risk of recurrence or aggravation of cerebral hemorrhage [OR = 0.85, 95% CI (0.67-1.06), P = 0.149]. Reinitiation of antiplatelet therapy was associated with a significantly lower risk of cerebral infarction [OR = 0.61, 95% CI (0.39-0.96), P = 0.033]. Restarting antiplatelet therapy after cerebral hemorrhage was not associated with a higher incidence rate of mortality [OR = 0.79, 95% CI (0.57, 1.08), P = 0.138], myocardial infarction [OR = 2.40, 95%CI (0.53,10.79), P = 0.253], hemiparesis [OR = 0.38, 95%CI (0.03,4.81), P = 0.451], neurological deficit [OR = 0.86,95%CI(0.32,2.33),P = 0.766]. CONCLUSION: Reinstitution of antiplatelet therapy after ICH was associated with a lower risk of thromboembolic complications.Resumption of antiplatelet therapy was not associated with a higher incidence of cerebral hemorrhage in Caucasians, but may be associated with a higher risk of cerebral hemorrhage recurrence in Asian populations.

[The prevalence and risk factors of intracranial non-traumatic hemorrhage in newborns]. / Rasprostranennost' i faktory riska vnutricherepnogo netravmaticheskogo krovoizliyaniya u novorozhdennykh.

OBJECTIVE: To assess the prevalence rate of intracranial hemorrhage in newborns and to detect the size of the relative risk for different characteristics of the background of intrauterine development according to the materials of the Republican Prenatal Center. MATERIAL AND METHODS: The study was conducted on the basis of the Republican Prenatal Center of the Azerbaijan Republic. All newborns (996 children) (birth weight - 500 grams or more, gestational age - over 22 completed weeks) have been examined by a neuropathologist. If there were signs of any neurological abnormalities, an ultrasound examination of the brain was performed. RESULTS: The prevalence rate of intracranial non-traumatic hemorrhage (INTH) among newborns was 15.66% (4.8% among full-term, 48.8% among premature). Depending on mother's age the prevalence rate of INTH changed from 12.7% (mother's age 20-24 years) to 23.0% (mother's age 35 years or more). CONCLUSION: The risk of INTH statistically significantly increased with maternal age 35 years or more, with 4 or more births, with the birth of a fetus weighing up to 2500 and more than 4000 grams, with a gestational age of less than 37 weeks, with multiple pregnancies and with vaginal delivery.

Timing of Anticoagulation Resumption and Risk of Ischemic and Hemorrhagic Complications in Patients With ICH and Mechanical Heart Valves.

BACKGROUND AND OBJECTIVES: In patients with mechanical heart valves and recent intracranial hemorrhage (ICH), clinicians need to balance the risk of thromboembolism during the period off anticoagulation and the risk of hematoma expansion on anticoagulation. The optimal timing of anticoagulation resumption is unknown. We aimed to investigate the relationship between reversal therapy and ischemic stroke, between duration off anticoagulation and risk of ischemic strokes or systemic embolism and between timing of anticoagulation resumption and risk of rebleeding and ICH expansion. METHODS: We conducted a retrospective cohort observational study in 3 tertiary hospitals. Consecutive adult patients with mechanical heart valves admitted for ICH between January 1, 2000, and July 13, 2022, were included. The primary end points of our study were thromboembolic events (cerebral, retinal, or systemic) while off anticoagulation and ICH expansion after anticoagulation resumption (defined by the following criteria: increase by one-third in intracerebral hematoma volume, increase by one-third in convexity subdural hemorrhage diameter, or visually unequivocal expansion of other ICH locations to the naked eye). RESULTS: A total of 171 patients with mechanical heart valves who experienced ICH were included in the final analysis. Most of the patients (79.5%) received reversal therapy for anticoagulation. Patients who received anticoagulation reversal therapy did not have increased risk of thromboembolic complications. Time off anticoagulation was not associated with risk of ischemic stroke; only 2 patients had a stroke within 7 days of the ICH, and both had additional major risk factors of thromboembolism. The rate of ischemic stroke/transient ischemic attack while off anticoagulation was lower than the rate of ICH expansion once anticoagulation was resumed (6.4% vs 9.9%). Furthermore, patients who developed ICH expansion had higher mortality compared with patients who had ischemic stroke while being off anticoagulation (41% vs 9%). Use of intravenous heparin bridging upon resumption of warfarin was strongly associated with increased risk of ICH expansion as compared with restarting warfarin without a heparin bridge. DISCUSSION: Withholding anticoagulation for at least 7 days after ICH may be safe in patients with mechanical heart valves. Heparin bridging during anticoagulation resumption may be associated with increased risk of bleeding.

Incidence and outcomes of delayed intracranial hemorrhage: a population-based cohort study.

Head trauma is a common reason for emergency department (ED) visits. Delayed intracranial hemorrhage (ICH) in patients with minor head trauma is a major concern, but controversies exist regarding the incidence of delayed ICH and discharge planning at the ED. This study aimed to determine the incidence of delayed ICH in adults who developed ICH after a negative initial brain computed tomography (CT) at the ED and investigate the clinical outcomes for delayed ICH. This nationwide population cohort study used data from the National Health Insurance Service of Korea from 2013 to 2019. Adult patients who presented to an ED due to trauma and were discharged after a negative brain CT examination were selected. The main outcomes were the incidence of ICH within 14 days after a negative brain CT at initial ED visit and the clinical outcomes of patients with and without delayed ICH. The study patients were followed up to 1 year after the initial ED discharge. Cox proportional hazard regression analysis was used to estimate the hazard ratio for all-cause 1-year mortality of delayed ICH. During the 7-year study period, we identified 626,695 adult patients aged 20 years or older who underwent brain CT at the ED due to minor head trauma, and 2666 (0.4%) were diagnosed with delayed ICH within 14 days after the first visit. Approximately two-thirds of patients (64.3%) were diagnosed with delayed ICH within 3 days, and 84.5% were diagnosed within 7 days. Among the patients with delayed ICH, 71 (2.7%) underwent neurosurgical intervention. After adjustment for age, sex, Charlson Comorbidity Index, and insurance type, delayed ICH (adjusted hazard ratio, 2.15; 95% confidence interval, 1.86-2.48; p < 0.001) was significantly associated with 1-year mortality. The incidence of delayed ICH was 0.4% in the general population, with the majority diagnosed within 7 days. These findings suggest that patient discharge education for close observation for a week may be a feasible strategy for the general population.

"Pediatric Spontaneous Intracranial Dissecting Aneurysms: Impact of Ischemic and Hemorrhagic Manifestations on Endovascular Treatment Strategies - Insights from a Developing World Setting".

BACKGROUND: Pediatric spontaneous intracranial dissecting aneurysms are rare, but systematic studies comparing hemorrhagic and ischemic presentations are lacking. This study addresses gaps in understanding their epidemiology, clinical presentation, management, and outcome. METHODS: A retrospective analysis of 23 pediatric patients with nontraumatic intracranial dissecting aneurysms treated between July 2018 and December 2023 was conducted. Patients were divided into 2 groups based on presentation: hemorrhagic (n = 16) and ischemic (n = 7). Clinical data were analyzed, including demographics, radiologic findings, treatment modalities, and outcomes. RESULTS: Clinical presentations varied, with limb weakness being more prevalent in hemorrhagic cases (P = 0.014), while headache and seizures were more common in ischemic cases. Angiographic analysis revealed distinct patterns, with hemorrhagic cases showing more distal involvement on vessel segments with stenosis and dilatation (pearl string sign). At the same time, the ischemic group exhibited the double-lumen sign. Various treatments, including microsurgery and endovascular techniques, were utilized, with perioperative complications observed, including one mortality in a hemorrhagic case. Multiple regression analysis identified significant risk factors for perioperative complications, namely, the configuration of the dissecting aneurysm (P = 0.016) and the type of presentation (P = 0.0006). Long-term Glasgow Outcome Scores were comparable, but patients with hemorrhagic manifestations experienced prolonged hospital and ICU stays (P = 0.001). CONCLUSIONS: Pediatric intracranial dissecting aneurysms, particularly hemorrhagic cases, are associated with severe neurologic deficits and higher perioperative complications. Despite similar long-term outcomes, hemorrhagic cases require prolonged hospitalization, increasing treatment costs. Optimizing management strategies for pediatric intracranial dissecting aneurysms, especially those with hemorrhagic features, is essential to improve outcomes and reduce healthcare expenditures.

Association of early changes in arterial carbon dioxide with acute brain injury in adult patients with extracorporeal membrane oxygenation: A ten-year retrospective study in a German tertiary care hospital.

PURPOSE: To assess the association between fluctuations of arterial carbon dioxide early after start of extracorporeal membrane oxygenation (ECMO) with intracranial hemorrhage (ICH) or ischemic stroke (IS). MATERIALS AND METHODS: This single-center retrospective study included patients who required ECMO for circulatory or respiratory failure between January 2011 and April 2021 and for whom a cerebral computed tomography (cCT) scan was available. Multivariable logistic regression models were fitted to evaluate the association between the relative change of arterial carbon dioxide (RelΔPaCO2) and ICH, IS or a composite of ICH, IS, and mortality. RESULTS: In 618 patients (venovenous ECMO: n = 295; venoarterial ECMO: n = 323) ICH occurred more frequently in patients with respiratory failure (19.0%) compared with patients with circulatory failure (6.8%). Conversely, the incidence of IS was higher in patients with circulatory failure (19.2%) compared with patients with respiratory failure (4.7%). While patients with ECMO for respiratory failure were more likely to have ICH (OR 3.683 [95% CI: 1.855;7.309], p < 0.001), they had a lower odds for IS (OR 0.360 [95%CI: 0.158;0.820], p = 0.015) compared with patients with circulatory failure. There was no significant association between RelΔPaCO2 and ICH or IS. CONCLUSIONS: Irrespective of the indication for ECMO, we did not find a significant association between the relative change in PaCO2 early after ECMO initiation and acute brain injury. Aside from early PaCO2 decline at cannulation, future studies should address fluctuations of PaCO2 throughout the course of ECMO support and their effect on acute brain injury.

Deep Learning to Detect Intracranial Hemorrhage in a National Teleradiology Program and the Impact on Interpretation Time.

The diagnostic performance of an artificial intelligence (AI) clinical decision support solution for acute intracranial hemorrhage (ICH) detection was assessed in a large teleradiology practice. The impact on radiologist read times and system efficiency was also quantified. A total of 61 704 consecutive noncontrast head CT examinations were retrospectively evaluated. System performance was calculated along with mean and median read times for CT studies obtained before (baseline, pre-AI period; August 2021 to May 2022) and after (post-AI period; January 2023 to February 2024) AI implementation. The AI solution had a sensitivity of 75.6%, specificity of 92.1%, accuracy of 91.7%, prevalence of 2.70%, and positive predictive value of 21.1%. Of the 56 745 post-AI CT scans with no bleed identified by a radiologist, examinations falsely flagged as suspected ICH by the AI solution (n = 4464) took an average of 9 minutes 40 seconds (median, 8 minutes 7 seconds) to interpret as compared with 8 minutes 25 seconds (median, 6 minutes 48 seconds) for unremarkable CT scans before AI (n = 49 007) (P < .001) and 8 minutes 38 seconds (median, 6 minutes 53 seconds) after AI when ICH was not suspected by the AI solution (n = 52 281) (P < .001). CT scans with no bleed identified by the AI but reported as positive for ICH by the radiologist (n = 384) took an average of 14 minutes 23 seconds (median, 13 minutes 35 seconds) to interpret as compared with 13 minutes 34 seconds (median, 12 minutes 30 seconds) for CT scans correctly reported as a bleed by the AI (n = 1192) (P = .04). With lengthened read times for falsely flagged examinations, system inefficiencies may outweigh the potential benefits of using the tool in a high volume, low prevalence environment. Keywords: Artificial Intelligence, Intracranial Hemorrhage, Read Time, Report Turnaround Time, System Efficiency Supplemental material is available for this article. © RSNA, 2024.

Intensive Versus Moderate Statin-Based Therapies in Patients With Mild Ischemic Stroke: A Prospective Multicenter Cohort Study.

BACKGROUND: Statins are widely used for treating patients with ischemic stroke at risk of secondary cerebrovascular events. It is unknown whether Asian populations benefit from more intensive statin-based therapy for stroke recurrence. Therefore, in the present study we evaluated the effectiveness and safety of high-dose and moderate-dose statins for patients who had experienced mild ischemic stroke during the acute period. METHODS AND RESULTS: This multicenter prospective study included patients with mild ischemic stroke who presented within 72 hours of symptom onset. The outcomes of patients in the high-intensity and moderate-intensity statin treatment groups were compared, with the main efficacy outcome being stroke recurrence and the primary safety end point being intracranial hemorrhage. The propensity score matching method was employed to control for imbalances in baseline variables. Subgroup analyses were conducted to evaluate group differences. In total, the data of 2950 patients were analyzed at 3 months, and the data of 2764 patients were analyzed at 12 months due to loss to follow-up. According to the multivariable Cox analyses adjusted for potential confounders, stroke recurrence occurred similarly in the high-intensity statin and moderate-intensity statin groups (3 months: adjusted hazard ratio [HR], 1.12 [95% CI, 0.85-1.49]; P=0.424; 12 months: adjusted HR, 1.08 [95% CI, 0.86-1.34]; P=0.519). High-intensity statin therapy was associated with an increased risk of intracranial hemorrhage (3 months: adjusted HR, 1.81 [95% CI, 1.00-3.25]; P=0.048; 12 months: adjusted HR, 1.86 [95% CI, 1.10-3.16]; P=0.021). The results from the propensity score-matched analyses were consistent with those from the Cox proportional hazards analysis. CONCLUSIONS: Compared with moderate-intensity statin therapy, high-dose statin therapy may not decrease the risk of mild, noncardiogenic ischemic stroke recurrence but may increase the risk of intracranial hemorrhage. REGISTRATION: URL: www.chictr.org.cn/. Unique Identifier: ChiCTR1900025214.

Incidence and clinical analysis of asymptomatic intracranial hemorrhage in neonates with cerebral hypoxic-ischaemic risk based on multisequence MR images.

The incidence and clinical distribution of intracranial haemorrhage (ICH) in neonates at risk of cerebral hypoxia-ischaemia have not been reported in specific studies. Based on conventional magnetic resonance imaging (MRI) versus susceptibility weighted imaging (SWI), this study aimed to analyse the occurrence of asymptomatic ICH in newborns with or without risk of cerebral hypoxia-ischaemia and to accumulate objective data for clinical evaluations of high-risk neonates and corresponding response strategies. 317 newborns were included. MRI revealed that the overall incidence of ICH was 59.31%. The most common subtype was intracranial extracerebral haemorrhage (ICECH) which included subarachnoid haemorrhage (SAH) and subdural haemorrhage (SDH). ICECH accounted for 92.02% of ICH. The positive detection rate of ICECH by SWI was significantly higher than that by T1WI. The incidence of total ICH, ICECH and SAH was greater among children who were delivered vaginally than among those who underwent caesarean delivery. Asymptomatic neonatal ICH may be a common complication of the neonatal birth process, and SWI may improve the detection rate. Transvaginal delivery and a weight greater than 2500 g were associated with a high incidence of ICECH in neonates. The impact of neonatal cerebral hypoxia-ischaemia risk factors on the occurrence of asymptomatic ICH may be negligible.

Early postoperative acetylsalicylic acid administration does not increase the risk of postoperative intracranial bleeding in patients with spontaneous intracerebral hemorrhage.

Administration of acetylsalicylic acid (ASA) at early stage after surgery for spontaneous intracerebral hemorrhage (SICH) may increase the risk of postoperative intracranial bleeding (PIB), because of potential inhibition of platelet function. This study aimed to investigate whether early ASA administration after surgery was related to increased risk of PIB. This retrospective study enrolled SICH patients receiving surgery from September 2019 to December 2022 in seven medical institution. Based on postoperative ASA administration, patients who continuously received ASA more than three days within seven days post-surgery were identified as ASA users, otherwise as non-ASA users. The primary outcome was symptomatic PIB events within seven days after surgery. Incidence of PIB was compared between ASA users and non-ASA users using survival analysis. This study included 744 appropriate patients from 794 SICH patients. PIB occurred in 42 patients. Survival analysis showed no statistical difference between ASA users and non-ASA users in incidence of PIB (P = 0.900). Multivariate Cox analysis demonstrated current smoker (hazard ratio [HR], 2.50, 95%CI, 1.33-4.71, P = 0.005), dyslipidemia (HR = 3.03; 95%CI, 1.31-6.99; P = 0.010) and pre-hemorrhagic antiplatelet therapy (HR = 3.05; 95% CI, 1.64-5.68; P < 0.001) were associated with PIB. Subgroup analysis manifested no significant difference in incidence of PIB between ASA users and non-ASA users after controlling the effect from factors of PIB (i.e., sex, age, current smoker, regular drinker, dyslipidemia, pre-hemorrhagic antiplatelet therapy and hematoma location). This study revealed that early ASA administration to SICH patients after surgery was not related to increased risk of PIB.

Time-in-therapeutic-range defined warfarin and direct oral anticoagulants in atrial fibrillation: a Nationwide Cohort Study.

BACKGROUND: Little is known how individual time-in-therapeutic-range (TTR) impacts the effectiveness and safety of warfarin therapy compared to direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF). OBJECTIVE: To compare the effectiveness and safety of standard dose DOACs to warfarin in patients with AF, while categorizing warfarin treated patients into quartiles based on their individual TTR. MATERIALS AND METHODS: We conducted a nationwide study including all patients with new-onset AF between 2011 and 2018 in Finland. Hazard ratios (HR) were calculated using Cox regression analysis with the inverse probability of treatment weighted method to assess the risks of ischaemic stroke (IS), intracranial haemorrhage (ICH) and mortality for users of apixaban (n = 12,426), dabigatran (n = 4545), rivaroxaban (n = 12,950) and warfarin (n = 43,548). RESULTS: The median TTR for warfarin users was 72%. Compared to the second best TTR quartile (reference), the risk of IS was higher in the two poorest TTR quartiles, and lower in the best TTR quartile and on rivaroxaban [2.35 (95% confidence interval, 1.85-2.85), 1.44 (1.18-1.75), 0.60 (0.47-0.77) and 0.72 (0.56-0.92)]. These differences were non-significant for apixaban and dabigatran. HR of ICH was 6.38 (4.88-8.35) and 1.87 (1.41-2.49) in the two poorest TTR groups, 1.44 (1.02-1.93) on rivaroxaban, and 0.58 (0.40-0.85) in the best TTR group compared to the reference group. Mortality was higher in the two poorest TTR groups and lowest in the best TTR group. CONCLUSIONS: The outcome was unsatisfactory in the two lowest TTR quartiles - in half of the patients treated with warfarin. The differences between the high TTR groups and standard dose DOACs were absent or modest.

Comorbidity burden and outcomes after mechanical thrombectomy for large vessel occlusion: A retrospective analysis.

OBJECTIVES: Patients with acute ischemic stroke (AIS) often have an accumulation of pre-existing comorbidities, but its clinical impact on outcomes after mechanical thrombectomy (MT) remains unknown. Therefore, we examined whether comorbidity burden before AIS onset could predict clinical outcomes after MT. METHODS: In this retrospective cohort, we enrolled consecutive patients with community-onset AIS who underwent MT between April 2016 and December 2021. To evaluate each patient's comorbidity burden, we calculated Charlson comorbidity index (CCI), then classified the patients into the High CCI (≥ 3) and the Low CCI (< 3) groups. The primary outcome was a good neurological outcome at 90 days, defined as a modified Rankin scale 0-2 or no worse than the previous daily conditions. All-cause mortality at 90 days and hemorrhagic complications after MT were also compared between the two groups. We estimated the odds ratios and their confidence intervals using a multivariable logistic regression model. RESULTS: A total of 388 patients were enrolled, of whom 86 (22.2%) were classified into the High CCI group. Patients in the High CCI group were less likely to achieve a good neurological outcome (adjusted odds ratio of 0.26 [95% confidence interval, 0.12-0.58]). Moreover, symptomatic intracranial hemorrhage was more common in the High CCI (14.0% vs. 4.6%; adjusted odds ratio, 4.10 [95% confidence interval, 1.62-10.3]). CONCLUSIONS: Comorbidity burden assessed by CCI was associated with clinical outcomes after MT. CCI has the potential to become a simple and valuable tool for predicting neurological prognosis among patients with AIS and MT.

Low caveolin-1 levels and symptomatic intracranial haemorrhage risk in large-vessel occlusive stroke patients after endovascular thrombectomy.

BACKGROUND AND PURPOSE: Caveolin-1 (Cav-1) is reported to mediate blood-brain barrier integrity after ischaemic stroke. Our purpose was to assess the role of circulating Cav-1 levels in predicting symptomatic intracranial haemorrhage (sICH) amongst ischaemic stroke patients after endovascular thrombectomy (EVT). METHODS: Patients with large-vessel occlusive stroke after EVT from two stroke centres were prospectively included. Serum Cav-1 level was tested after admission. sICH was diagnosed according to the Heidelberg Bleeding Classification. RESULTS: Of 325 patients (mean age 68.6 years; 207 men) included, 47 (14.5%) were diagnosed with sICH. Compared with patients without sICH, those with sICH had a lower concentration of Cav-1. After adjusting for potential confounders, multivariate regression analysis demonstrated that the increased Cav-1 level was associated with a lower sICH risk (odds ratio 0.055; 95% confidence interval 0.005-0.669; p = 0.038). Similar results were obtained when Cav-1 levels were analysed as a categorical variable. Using a logistic regression model with restricted cubic splines, a linear and negative association of Cav-1 concentration was found with sICH risk (p = 0.001 for linearity). Furthermore, the performance of the conventional risk factors model in predicting sICH was substantially improved after addition of the Cav-1 levels (integrated discrimination index 2.7%, p = 0.002; net reclassification improvement 39.7%, p = 0.007). CONCLUSIONS: Our data demonstrate that decreased Cav-1 levels are related to sICH after EVT. Incorporation of Cav-1 into clinical decision-making may help to identify patients at a high risk of sICH and warrants further consideration.

Incidence of intracranial bleeding in mild traumatic brain injury patients taking oral anticoagulants: a systematic review and meta-analysis.

BACKGROUND: Traumatic brain injury (TBI) is one of the leading causes of disability and death worldwide. Most TBI cases occur in older people, because they are at a higher risk of accidental falling. As the population ages, the use of anticoagulants is increasing. Some serious complications of TBI, such as intracranial hemorrhage (ICH), may occur even in mild cases. According to the current guidelines regarding managing mild TBI patients, a CT head scan is recommended for all patients receiving anticoagulation. We aim to assess the incidence of ICH in patients with mild TBI taking oral anticoagulants. METHODS: Our systematic review and meta-analysis were performed using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) checklist. The protocol was registered in PROSPERO (CRD42024503086). Twenty-eight studies evaluating patients with a mild TBI from ten countries with a total sample size of 11,172, 5671 on DOACs, and 5501 on VKAs were included in our meta-analysis. RESULTS: The random-effects overall incidence of ICH among oral anticoagulated patients with mild TBI was calculated to be 9.4% [95% CI 7.2-12.1%, I2 = 89%]. The rates of immediate ICH for patients taking DOACs and VKAs were 6.4% and 10.5%, respectively. The overall rate of immediate ICH in anticoagulated mild TBI patients was 8.5% [95% CI 6.6-10.9%], with a high heterogeneity between studies (I2 = 88%). Furthermore, the rates of delayed ICH in patients with mild TBI taking DOACs and VKAs were 1.6% and 1.9%, respectively. The overall incidence of delayed ICH among oral anticoagulated mild TBI patients was 1.7% [95% CI 1-2.8%, I2 = 79%]. The overall rate of ICH among mild TBI patients taking DOAC was calculated to be 7.3% [95% CI 5.2-10.3%], with significant heterogeneity between studies (I2 = 79%). However, the overall ICH rate is higher in patients who take only VKAs 11.3% [95% CI 8.6-14.7%, I2 = 83%]. Patients on DOACs were at lower risk of ICH after mild TBI compared to patients on VKAs (OR = 0.64, 95% CI 0.48-0.86, p < 0.01, I2 = 28%). CONCLUSION: Our meta-analysis confirms the need for performing brain CT scan in patients with mild TBI patients who receive oral anticoagulants before injury. Due to limited data, further multi-center, prospective studies are warranted to confirm the true incidence of traumatic ICH in patients on anticoagulants.

Pediatric Patients with Intracranial Arteriovenous Malformations: Trends in Emergency Room Presentation.

BACKGROUND: Pediatric intracranial arteriovenous malformation (AVM) patients are commonly admitted to the emergency room (ER). Increasing patient utilization of the ER has been associated with healthcare disparities and a trend of decreased efficiency. The aim of this study was to evaluate the trends of pediatric AVM ER admissions over recent years and identify factors associated with health care resource utilization and outcomes. METHODS: The 2016-2019 National Inpatient Sample was queried for patients under the age of 18 admitted with AVM. Cases of admission through the ER were identified. Demographic and severity factors associated with ER admission were explored using comparative and regression statistics. RESULTS: Of 3875 pediatric patients with AVM admitted between 2016 and 2019, 1280 (33.0%) were admitted via the ER. Patients admitted via the ER were more likely to be in the lowest median income category (P < 0.001), on Medicaid insurance (P = 0.008), or in the South (P < 0.001) than patients admitted otherwise. There was increased severity and increased rates of intracranial hemorrhage (ICH) in patients admitted via the ER (P < 0.001). Finally, there were increasing trends in ER admissions and ICH throughout the years. CONCLUSIONS: ER admission of pediatric AVM patients with ICH is increasing and is associated with a distinct socioeconomic profile and increased healthcare resource utilization. These findings may reflect decreased access to more advanced diagnostic modalities, primary care, and other important resources. Identifying populations with barriers to care is likely an important component of policy aimed at decreasing the risk of severe disease presentation.

Causal relationship between gut microbiota and intracranial hemorrhage: A two-sample Mendelian randomization study.

Patients with intracranial hemorrhage (ICH) usually have an imbalance in the gut microbiota (GM); however, whether this is a causal correlation remains unclear. This study used summary data from an open genome-wide association study to conduct double-sample Mendelian randomization (MR) to test the causal correlation between GM and ICH. First, we used a cutoff value of P < 10E-5 to select single nucleotide polymorphisms critical for each GM. Inverse variance weighted, weighted median, and MR-PRESSO methods were used to evaluate the strength of this causal association. Finally, functional maps and annotations from genome-wide association studies were used to determine the biological functions of the genes. MR analysis revealed that Rikenellaceae RC9 gut group was significantly positively correlated with ICH risk. For every unit increase in Rikenellaceae RC9 gut group, the relative risk of ICH increased by 34.4%(P = 4.62E-04). Rhodospirillales, Terrisporobacter, Veillonellaceae, Coprococcus 3, unknown genus, Alphaproteobacteria, and Allisonella groups were negatively correlated with the risk of ICH, while Anaerofilum, Eubacteriumbrachy group, Clostridia, Howardella, and Romboutsia were negatively correlated with the risk of ICH. Nonetheless, the specific role of single nucleotide polymorphisms gene enrichment requires further investigation. This study suggests the causal effect on ICH. The discovery of >10 GMs associated with ICH could be used to prevent and treat ICH.

The prevalence of clinically relevant delayed intracranial hemorrhage in head trauma patients treated with oral anticoagulants is very low: a retrospective cohort register study.

BACKGROUND: Current guidelines from Scandinavian Neuro Committee mandate a 24-hour observation for head trauma patients on anticoagulants, even with normal initial head CT scans, as a means not to miss delayed intracranial hemorrhages. This study aimed to assess the prevalence, and time to diagnosis, of clinically relevant delayed intracranial hemorrhage in head trauma patients treated with oral anticoagulants. METHOD: Utilizing comprehensive two-year data from Region Skåne's emergency departments, which serve a population of 1.3 million inhabitants, this study focused on adult head trauma patients prescribed oral anticoagulants. We identified those with intracranial hemorrhage within 30 days, defining delayed intracranial hemorrhage as a bleeding not apparent on their initial CT head scan. These cases were further defined as clinically relevant if associated with mortality, any intensive care unit admission, or neurosurgery. RESULTS: Out of the included 2,362 head injury cases (median age 84, 56% on a direct acting oral anticoagulant), five developed delayed intracranial hemorrhages. None of these five cases underwent neurosurgery nor were admitted to an intensive care unit. Only two cases (0.08%, 95% confidence interval [0.01-0.3%]) were classified as clinically relevant, involving subdural hematomas in patients aged 82 and 87 years, who both subsequently died. The diagnosis of these delayed intracranial hemorrhages was made at 4 and 7 days following initial presentation to the emergency department. CONCLUSION: In patients with head trauma, on oral anticoagulation, the incidence of clinically relevant delayed intracranial hemorrhage was found to be less than one in a thousand, with detection occurring four days or later after initial presentation. This challenges the effectiveness of the 24-hour observation period recommended by the Scandinavian Neurotrauma Committee guidelines, suggesting a need to reassess these guidelines to optimise care and resource allocation. TRIAL REGISTRATION: This is a retrospective cohort study, does not include any intervention, and has therefore not been registered.