[Impact of different angles of pulmonary surfactant administration on bronchopulmonaryplasia and intracranial hemorrhage in preterm infants: a prospective randomized controlled study]. / ä¸åŒè§’åº¦æ³¨å ¥è‚ºè¡¨é¢æ´»æ€§ç‰©è´¨å¯¹æ—©äº§å„¿æ”¯æ°”ç®¡è‚ºå‘è‚²ä¸è‰¯å’Œé¢ å† å‡ºè¡€çš„å½±å“ï¼šä¸€é¡¹å‰çž»æ€§éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To investigate the effects of different angles of pulmonary surfactant (PS) administration on the incidence of bronchopulmonary dysplasia and intracranial hemorrhage in preterm infants. METHODS: A prospective study was conducted on 146 preterm infants (gestational age <32 weeks) admitted to the Department of Neonatology, Provincial Hospital Affiliated to Anhui Medical University from January 2019 to May 2023. The infants were randomly assigned to different angles for injection of pulmonary surfactant groups: 0° group (34 cases), 30° group (36 cases), 45° group (38 cases), and 60° group (38 cases). Clinical indicators and outcomes were compared among the groups. RESULTS: The oxygenation index was lower in the 60° group compared with the other three groups, with shorter invasive ventilation time and oxygen use time, and a lower incidence of bronchopulmonary dysplasia than the other three groups (P<0.05). The incidence of intracranial hemorrhage was lower in the 60° group compared to the 0° group (P<0.05). The cure rate in the 60° group was higher than that in the 0° group and the 30° group (P<0.05). CONCLUSIONS: The clinical efficacy of injection of pulmonary surfactant at a 60° angle is higher than other angles, reducing the incidence of intracranial hemorrhage and bronchopulmonary dysplasia in preterm infants.

Low-Dose Aspirin and the Risk of Stroke and Intracerebral Bleeding in Healthy Older People: Secondary Analysis of a Randomized Clinical Trial.

Importance: Low-dose aspirin has been widely used for primary and secondary prevention of stroke. The balance between potential reduction of ischemic stroke events and increased intracranial bleeding has not been established in older individuals. Objective: To establish the risks of ischemic stroke and intracranial bleeding among healthy older people receiving daily low-dose aspirin. Design, Setting, and Participants: This secondary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) randomized, double-blind, placebo-controlled trial of daily low-dose aspirin was conducted among community-dwelling people living in Australia or the US. Participants were older adults free of symptomatic cardiovascular disease. Recruitment took place between 2010 and 2014, and participants were followed up for a median (IQR) of 4.7 (3.6-5.7) years. This analysis was completed from August 2021 to March 2023. Interventions: Daily 100-mg enteric-coated aspirin or matching placebo. Main Outcomes and Measures: Stroke and stroke etiology were predetermined secondary outcomes and are presented with a focus on prevention of initial stroke or intracranial bleeding event. Outcomes were assessed by review of medical records. Results: Among 19 114 older adults (10 782 females [56.4%]; median [IQR] age, 74 [71.6-77.7] years), 9525 individuals received aspirin and 9589 individuals received placebo. Aspirin did not produce a statistically significant reduction in the incidence of ischemic stroke (hazard ratio [HR], 0.89; 95% CI, 0.71-1.11). However, a statistically significant increase in intracranial bleeding was observed among individuals assigned to aspirin (108 individuals [1.1%]) compared with those receiving placebo (79 individuals [0.8%]; HR, 1.38; 95% CI, 1.03-1.84). This occurred by an increase in a combination of subdural, extradural, and subarachnoid bleeding with aspirin compared with placebo (59 individuals [0.6%] vs 41 individuals [0.4%]; HR, 1.45; 95% CI, 0.98-2.16). Hemorrhagic stroke was recorded in 49 individuals (0.5%) assigned to aspirin compared with 37 individuals (0.4%) in the placebo group (HR, 1.33; 95% CI, 0.87-2.04). Conclusions and Relevance: This study found a significant increase in intracranial bleeding with daily low-dose aspirin but no significant reduction of ischemic stroke. These findings may have particular relevance to older individuals prone to developing intracranial bleeding after head trauma. Trial Registration: ISRCTN.org Identifier: ISRCTN83772183.

The safety and efficacy of periprocedural intravenous anticoagulants for acute ischemic stroke patients who underwent endovascular treatment: Sub-analysis of the RESCUE-Japan Registry 2.

The efficacy and safety of periprocedural anticoagulant therapy are still controversial. We investigated the effects of periprocedural anticoagulation on patients who underwent endovascular therapy (EVT) for acute ischemic stroke (AIS). The patients were dichotomized into two groups according to the use of intravenous anticoagulant during or within 24 h after EVT (AC or non-AC group). Primary outcome was defined as a modified Rankin Scale (mRS) score of 0-2 at 90 days. Safety outcomes were defined as any or symptomatic intracerebral hemorrhages (ICH). Among 1278 enrolled patients, 740 patients (57.9%) were in the AC group and the remaining 538 patients (42.1%) were in the non-AC group. The median dose of heparin was 5000 units intraoperatively, and 10,000 units /day postoperatively. In the AC group, hypercholesterolemia, higher pre-stroke modified Rankin Scale score, non-cardiac embolism etiology, higher rate of anticoagulant premedication, non-administration of t-PA (tissue plasminogen activator), later admission, and longer procedure time were observed. The rate of primary outcomes was not significantly different between the AC and non-AC groups (40.1% vs. 43.9%; adjusted odds ratio, 1.29; 95% CI, 0.96-1.73; p = 0.09). The incidence of any (26.2% vs. 25.7%; p = 0.80; adjusted odds ratio, 0.97; 95% CI, 0.72-1.22) and symptomatic (4.3% vs. 5.0%; p = 0.52; adjusted OR, 0.83; 95% CI, 0.46-1.51) intracranial hemorrhage within 72 h were not significantly different between the groups. Periprocedural anticoagulant therapy after acute revascularization did not relate to prognosis and intracranial hemorrhage after EVT.

Blood pressure management for secondary stroke prevention.

Hypertension is the most important vascular risk factor for stroke; therefore, optimal blood pressure (BP) management is essential for the prevention of recurrent stroke; lowering BP was shown to reduce the risk of recurrent stroke by 25-30%. A recent meta-analysis showed that intensive BP lowering to levels <130/80 mmHg significantly reduced the risk of recurrent stroke compared to standard management with BP levels <140/90 mmHg. The benefit of intensive BP management is evident with regard to a reduced risk of intracranial hemorrhage. Therefore, clinical practice guidelines have established a target BP of <130/80 mmHg. However, the target BP needs to be individualized. A stepped-care approach for cautious BP lowering (usually to levels <140/90 mmHg) is preferred for patients with severe diseases of the major cerebral vessels, who have a high risk of recurrent ischemic stroke. In contrast, more aggressive BP lowering (to levels <120/80 mmHg) tends to benefit patients at high risk of intracranial hemorrhage. The selection of BP management strategies should be guided by the risk of recurrent ischemic and hemorrhagic strokes.

Associations of Early Systolic Blood Pressure Control and Outcome After Thrombolysis-Eligible Acute Ischemic Stroke: Results From the ENCHANTED Study.

BACKGROUND AND PURPOSE: In thrombolysis-eligible patients with acute ischemic stroke, there is uncertainty over the most appropriate systolic blood pressure (SBP) lowering profile that provides an optimal balance of potential benefit (functional recovery) and harm (intracranial hemorrhage). We aimed to determine relationships of SBP parameters and outcomes in thrombolyzed acute ischemic stroke patients. METHODS: Post hoc analyzes of the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study), a partial-factorial trial of thrombolysis-eligible and treated acute ischemic stroke patients with high SBP (150-180 mm Hg) assigned to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) alteplase and intensive (target SBP, 130-140 mm Hg) or guideline-recommended (target SBP <180 mm Hg) treatment. All patients were followed up for functional status and serious adverse events to 90 days. Logistic regression models were used to analyze 3 SBP summary measures postrandomization: attained (mean), variability (SD) in 1-24 hours, and magnitude of reduction in 1 hour. The primary outcome was a favorable shift on the modified Rankin Scale. The key safety outcome was any intracranial hemorrhage. RESULTS: Among 4511 included participants (mean age 67 years, 38% female, 65% Asian) lower attained SBP and smaller SBP variability were associated with favorable shift on the modified Rankin Scale (per 10 mm Hg increase: odds ratio, 0.76 [95% CI, 0.71-0.82]; P<0.001 and 0.86 [95% CI, 0.76-0.98]; P=0.025) respectively, but not for magnitude of SBP reduction (0.98, [0.93-1.04]; P=0.564). Odds of intracranial hemorrhage was associated with higher attained SBP and greater SBP variability (1.18 [1.06-1.31]; P=0.002 and 1.34 [1.11-1.62]; P=0.002) but not with magnitude of SBP reduction (1.05 [0.98-1.14]; P=0.184). CONCLUSIONS: Attaining early and consistent low levels in SBP <140 mm Hg, even as low as 110 to 120 mm Hg, over 24 hours is associated with better outcomes in thrombolyzed acute ischemic stroke patients. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01422616.

Stroke Prevention by Anticoagulants in Daily Practice Depending on Atrial Fibrillation Pattern and Clinical Risk Factors.

Background and Purpose: The objective of the study was to assess the effectiveness of individual direct oral anticoagulants versus vitamin K antagonists for primary prevention of stroke (ischemic and hemorrhagic) in routine clinical practice in patients with various clinical risk factors depending on their atrial fibrillation (AF) patterns. Methods: A nested case-referent study was conducted using data from 2 national registries of patients with stroke and AF. Stroke cases with previous history of AF were matched to up to 2 randomly selected referent patients with AF and no stroke. The association of individual anticoagulant use with ischemic or hemorrhagic stroke was studied in patients with or without permanent AF using multivariable conditional logistic models, controlled for clinically significant risk factors and multiple other cardiovascular risk factors. Results: In total, 2586 stroke cases with previous AF and 4810 nonstroke referent patients with AF were retained for the study. Direct oral anticoagulant users had lower odds of stroke of any type than vitamin K antagonist users: the adjusted-matched OR for ischemic stroke were 0.70 (95% CI, 0.50­0.98) for dabigatran, 0.68 (95% CI, 0.53­0.86) for rivaroxaban, and 0.73 (95% CI, 0.52­1.02) for apixaban while for hemorrhagic stroke they were 0.31 (95% CI, 0.14­0.68), 0.64 (95% CI, 0.39­1.06), and 0.70 (95% CI, 0.33­1.49), respectively. The effects of individual direct oral anticoagulants relative to vitamin K antagonists were similar in permanent AF and nonpermanent AF patients. Conclusions: Similar results were observed for each direct oral anticoagulant in real life as those observed in the pivotal clinical trials. The pattern of AF did not affect the outcome.

Big Data Analysis of the Risk of Intracranial Hemorrhage in Korean Populations Taking Low-Dose Aspirin.

OBJECTIVES: Aspirin has traditionally been used as an analgesic and anti-inflammatory drug; however, low-dose aspirin is known to increase the risk of gastrointestinal and intracranial hemorrhage. In this study, the risk of intracranial hemorrhage in patients taking low-dose aspirin was assessed. MATERIALS AND METHODS: We used the Standard Sample Cohort DB dataset from the National Health Insurance Sharing Service of Korea. This dataset includes details of medical care and prescriptions for patients who used hospital services during a 14-year period throughout Korea. Of approximately 1 million total patients, data from 746,703 adults over the age of 30 years were included for analysis. An Χ2 test was performed to assess the effect of low-dose aspirin on intracranial hemorrhage. In addition, the relationship between use of low-dose aspirin and intracranial hemorrhage was analyzed using multiple logistic regression with consideration of all confounding variables. RESULTS: The results revealed no significant positive correlations between the use of low-dose aspirin and intracranial hemorrhage requiring hospitalization. CONCLUSIONS: Big data analysis of 746,703 patients in Korea over a period of 14 years showed that serious intracranial hemorrhage requiring hospitalization was unrelated to low-dose aspirin use. Moreover, low-dose aspirin use reduced the risk of intracranial hemorrhage in Korean populations.

Continuous Glibenclamide Prevents Hemorrhagic Transformation in a Rodent Model of Severe Ischemia-Reperfusion.

BACKGROUND: Endovascular thrombectomy (EVT) is highly effective but may also lead to hemorrhagic transformation (HT) and edema, which may be more pronounced in severe ischemia. We sought to determine whether glibenclamide can attenuate HT and edema in a severe ischemia-reperfusion model that reflects EVT. METHODS: Using a transient middle cerebral artery occlusion (tMCAo) rodent model of stroke, we studied two rat cohorts, one without rt-PA and a second cohort treated with rt-PA. Glibenclamide or vehicle control was administered as an intravenous bolus at reperfusion, followed by continuous subcutaneous administration with an osmotic pump. RESULTS: Compared to vehicle control, glibenclamide improved neurological outcome (median 7, interquartile range [IQR 6-8] vs. control median 6 [IQR 0-6], p = 0.025), reduced stroke volume (323 ± 42 vs. 484 ± 60 mm3, p < 0.01), swelling volume (10 ± 4 vs. 28 ± 7%, p < 0.01) and water content (84 ± 1 vs. 85 ± 1%, p < 0.05). Glibenclamide administration also reduced HT based on ECASS criteria, densitometry (0.94 ± 0.1 vs. 1.15 ± 0.2, p < 0.01), and quantitative hemoglobin concentration (2.7 ± 1.5 vs. 6.2 ± 4.6 uL, p = 0.011). In the second cohort with rt-PA coadministration, concordant effects on HT were observed with glibenclamide. CONCLUSIONS: Taken together, these studies demonstrated that glibenclamide reduced the amount of edema and HT after severe ischemia. This study suggests that co-administration of glibenclamide may be worth further study in severe stroke patients treated with EVT with or without IV rt-PA.

On the Use of Digital Subtraction Angiography in Stereoelectroencephalography Surgical Planning to Prevent Collisions with Vessels.

OBJECTIVE: Stereoelectroencephalography (SEEG) consists of the implantation of microelectrodes for the electrophysiological characterization of epileptogenic networks. To reduce a possible risk of intracranial bleeding by vessel rupture during the electrode implantation, the stereotactic trajectories must follow avascular corridors. The use of digital subtraction angiography (DSA) for vascular visualization during planning is controversial due to the additional risk related to this procedure. Here we evaluate the utility of this technique for planning when the neurosurgeon has it available together with gadolinium-enhanced T1-weighted magnetic resonance sequence (T1-Gd) and computed tomography angiography (CTA). METHODS: Twenty-two implantation plans for SEEG were initially done using T1-Gd imaging (251 trajectories). DSA was only used later during the revision process. In 6 patients CTA was available at this point as well. We quantified the position of the closest vessel to the trajectory in each of the imaging modalities. RESULTS: Two thirds of the trajectories that appeared vessel free in the T1-Gd or CTA presented vessels in their proximity, as shown by DSA. Those modifications only required small shifts of both the entry and target point, so the diagnostic aims were preserved. CONCLUSIONS: T1-Gd and CTA, despite being the most commonly used techniques for SEEG planning, frequently fail to reveal vessels that are dangerously close to the trajectories. Higher-resolution vascular imaging techniques, such as DSA, can provide the neurosurgeon with crucial information about vascular anatomy, resulting in safer plans.

Timing, Outcome, and Risk Factors of Intracranial Hemorrhage in Acute Respiratory Distress Syndrome Patients During Venovenous Extracorporeal Membrane Oxygenation.

OBJECTIVES: Intracranial hemorrhage is a serious complication in patients receiving venovenous extracorporeal membrane oxygenation during treatment of the acute respiratory distress syndrome. We analyzed timing, outcome, and risk factors of intracranial hemorrhage in patients on venovenous extracorporeal membrane oxygenation. DESIGN: Retrospective cohort study. SETTING: Single acute respiratory distress syndrome referral center. PATIENTS: Patients receiving venovenous extracorporeal membrane oxygenation were identified from a cohort of 1,044 patients with acute respiratory distress syndrome. Patients developing an intracranial hemorrhage during venovenous extracorporeal membrane oxygenation therapy were compared with patients without evidence for intracranial hemorrhage. The primary objective was to assess the association of intracranial hemorrhage with 60-day mortality. Further objectives included the identification of risk factors for intracranial hemorrhage and the evaluation of clinical cutoff values. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 444 patients treated with venovenous extracorporeal membrane oxygenation, 49 patients (11.0% [95% CI, 8.3-14.4%]) developed an intracranial hemorrhage. The median time to intracranial hemorrhage occurrence was 4 days (95% CI, 2-7 d). Patients who developed an intracranial hemorrhage had a higher 60-day mortality compared with patients without intracranial hemorrhage (69.4% [54.4-81.3%] vs 44.6% [39.6-49.6%]; odds ratio 3.05 [95% CI, 1.54-6.32%]; p = 0.001). A low platelet count, a high positive end expiratory pressure, and a major initial decrease of Paco2 were identified as independent risk factors for the occurrence of intracranial hemorrhage. A platelet count greater than 100/nL and a positive end expiratory pressure less than or equal to 14 cm H2O during the first 7 days of venovenous extracorporeal membrane oxygenation therapy as well as a decrease of Paco2 less than 24 mm Hg during venovenous extracorporeal membrane oxygenation initiation were identified as clinical cutoff values to prevent intracranial hemorrhage (sensitivity 91% [95% CI, 82-99%], 94% [85-99%], and 67% [48-81%], respectively). CONCLUSIONS: Intracranial hemorrhage occurs early during venovenous extracorporeal membrane oxygenation and is a determinant for 60-day mortality. Appropriate adjustment of identified modifiable risk factors might lower the prevalence of intracranial hemorrhage during venovenous extracorporeal membrane oxygenation therapy.

Intentional Stent Stenosis to Prevent Hyperperfusion Syndrome after Carotid Artery Stenting for Extremely High-Grade Stenosis.

BACKGROUND AND PURPOSE: Intracranial hemorrhage due to hyperperfusion syndrome is a severe carotid artery stent placement complication of extremely high-grade stenosis, causing hemodynamic insufficiency. To prevent hyperperfusion syndrome, we attempted intentional residual stent stenosis and implemented "gentle" carotid artery stent placement, defined as carotid artery stent placement using a closed-cell stent coupled with slight balloon predilation, without balloon postdilation. Gradual stent expansion was expected. We investigated the incidence of hyperperfusion syndrome and long-term outcomes after gentle carotid artery stent placement. MATERIALS AND METHODS: We included patients who underwent carotid artery stent placement for extremely high-grade stenosis from January 2015 to March 2019. We defined extremely high-grade stenosis as carotid stenosis with conventional angiographic "slow flow" and a reduced MCA signal intensity on MRA. A reduced MCA signal intensity was defined as MCA with a relative signal intensity of <0.9 in the ipsilateral compared with the contralateral MCA. We evaluated the stent diameter, CBF on SPECT, hyperperfusion syndrome, and intracranial hemorrhage. We defined hyperperfusion syndrome as a triad of ipsilateral headache, seizure, and hemiparesis. RESULTS: Twenty-eight of the 191 patients met our inclusion criteria. After carotid artery stent placement, their median minimal stent diameter was 2.9 mm, which expanded to 3.9 mm at 4 months. Neither cerebral hyperperfusion syndrome nor intracranial hemorrhage occurred. CONCLUSIONS: The gentle carotid artery stent placement strategy for intentional residual stent stenosis may prevent hyperperfusion syndrome in high-risk patients. Stents spontaneously dilated in 4 months.

Outcomes in relation to antithrombotic therapy among patients with atrial fibrillation after percutaneous coronary intervention.

BACKGROUNDS: We investigated the prognostic impact of antithrombotic regimens at 1-year after percutaneous coronary intervention (PCI) among patients with atrial fibrillation (AF). METHOD AND RESULTS: A total of 13,278 AF patients who underwent PCI from 2009 to 2013 were selected from Korean National Health Insurance Service database. Patients were categorized by antithrombotic regimens at 1-year after PCI: (1) OAC with or without single antiplatelet (OAC±SAPT); (2) triple therapy (TT) and (3) antiplatelets (APT) only. After propensity score matching, composite ischaemia (death, myocardial infarction, and stroke), composite bleeding (intracranial hemorrhage and gastrointestinal bleeding), and a composite clinical outcome (composite ischaemia and bleeding) were compared. Of total population, 1,100 (8.3%), 746 (5.6%), and 11,432 (86.1%) were treated with OAC±SAPT, TT, and APT only, respectively. Compared to OAC±SAPT group, the TT group had significantly higher risk of the composite clinical outcome (hazard ratio [HR] 1.46, 95% confidence interval [CI] 1.00-2.13) attributed to a higher trend in both ischaemia (HR 1.63, 95% CI 0.99-2.67) and bleeding (HR 1.22, 95% CI 0.69-2.13). The APT only group showed a higher risk of ischaemia (HR 1.85, 95% CI 1.25-2.74), despite a lower risk of bleeding (HR 0.55, 95% CI 0.32-0.94) compared to OAC±SAPT group. CONCLUSIONS: OAC±SAPT was associated with better clinical outcomes compared to TT or APT only treatments, beyond 1-year after PCI among Asians with AF.

Therapeutic Effects of Iron Chelation in Atorvastatin-Induced Intracranial Hemorrhage of Zebrafish Larvae.

OBJECTIVE: Intracranial hemorrhage (ICH) catastrophically damages the cerebral vasculature, and severely compromises blood-brain barrier (BBB) function. The prognosis of ICH is poor due to the drastic and rapid progression of its pathology, and the lack of effective treatments presents a significant unmet clinical need. The present paper provides several evidences about the relationship between ICH bleeding status and mortality and the potential therapeutic effects of an iron chelator for ICH. METHODS: Zebrafish are a highly transparent animal model, allowing live imaging of the complex cerebral vasculature. Thus, to further elucidate ATV-induced ICH, we investigated the concentration- and time-dependent phenotypes of ATV-induced ICH with zebrafish larvae. RESULTS: The effects of ATV on mortality and ICH incidence in zebrafish larvae were concentration-dependent. Further, ATV treatment decreased vascular density of the hindbrain in a concentration-dependent manner, and hematoma volume was inversely correlated with ATV concentration. The number of cranial TUNEL-positive apoptotic cells was markedly increased 3 days post-fertilization. Importantly, the iron chelator deferasirox (DFR) decreased the incidence of ATV-induced ICH in zebrafish larvae. CONCLUSION: These findings provided insight into the pathology and regulatory mechanism of ATV-induced ICH, and demonstrated the therapeutic effects of iron chelators.

Who may benefit from lower dosages of intravenous tissue plasminogen activator? Results from a cluster data analysis.

BACKGROUND: The risk of symptomatic intracranial haemorrhage (sICH) after thrombolysis is low but severe. Lower dose of alteplase may reduce the risk of sICH. We aim to identify subsets of patients who could benefit from lower dose of alteplase compared with standard dose. METHODS: Data from two observational registries were pooled together. A total of 3479 patients who had acute ischaemic stroke were entered into the interaction tree model. The response variable was the rate of sICH per the definition of the National Institute of Neurological Disorders and Stroke Study. Clinical improvement was measured by the National Institutes of Health Stroke Scale (NIHSS) and defined as NIHSS 0 or 1 or an improvement of more than 4 points (within 7 days or at discharge). Rare event logistic regression was performed to analyse the OR of safety outcome. RESULTS: To optimise the interaction effect between tissue plasminogen activator (tPA) dosage (standard/lower) and patient subgroups, three subgroups based on the severity of stroke were identified: (1) NIHSS ≤4, (2) NIHSS between 5 and 14, and (3) NIHSS ≥15. The estimated difference of OR of having sICH was 2.71 (95% CI 0.80 to 7.69, p=0.10) for mild, 0.13 (95% CI 0.02 to 0.68, p=0.01) for moderate, and 0.65 (95% CI 0.19 to 2.55, p=0.52) for severe, respectively. In addition, patients who had moderate stroke treated with lower dose had comparable efficacy outcome (OR 1.23, 95% CI 0.71 to 2.13, p=0.45). CONCLUSION: Our analysis demonstrated that in patients who had moderate stroke, lower doses of alteplase are associated with significant sICH reduction and non-inferior performance in efficacy, compared with those in the standard dose group. TRIAL REGISTRATION NUMBER: The TIMS-China was a national prospective stroke registry on thrombolytic therapy using intravenous tPA in patients who had acute ischaemic stroke. The results were initially published in 2012 without a clinical trial registration number. The Shanghai Stroke Service System was registered at www.clinicaltrial.gov (NCT02735226).

Management of Anticoagulant Treatment and Anticoagulation-Related Complications in Nonagenarians.

Given the aging population, the burden of age-dependent diseases is growing. Despite this, elderly patients are often underrepresented in clinical trials and little data are available on current anticoagulant management and outcomes in this unique population, especially those aged 90 years or older. There is uncertainty, and a fear of "doing harm," that often leads to de-prescription of antithrombotic agents in nonagenarian patients. Decision-making concerning the use of anticoagulant treatment needs to balance the risk of thrombotic events against the risk of major bleeding, especially intracranial hemorrhage. In this perspective, the development of direct oral anticoagulants (DOACs), acting as direct and selective inhibitors of a specific step or enzyme of the coagulation cascade, has dramatically changed oral anticoagulant treatment. In fact, given the lower incidence of intracranial hemorrhage, the favorable overall efficacy and safety, and the lack of routine monitoring, DOACs are the currently recommended anticoagulant agents for the treatment of both atrial fibrillation and venous thromboembolism even in very elderly patients. However, given the limited data available on the management of anticoagulation in nonagenarians, a few unanswered questions remain. In this review, we focused on recent evidence for anticoagulant treatment in atrial fibrillation and venous thromboembolism along with management of anticoagulation-related bleeding in nonagenarians.

Treatment strategies for patients with atrial fibrillation and anticoagulant-associated intracranial hemorrhage: an overview of the pharmacotherapy.

INTRODUCTION: Oral anticoagulants (OAC) reduce stroke/systemic embolism and mortality risks in atrial fibrillation (AF). However, there is an inherent bleeding risk with OAC, where intracranial hemorrhage (ICH) is the most feared, disabling, and lethal complication of this therapy. Therefore, the optimal management of OAC-associated ICH is not well defined despite multiple suggested strategies. AREAS COVERED: In this review, the authors describe the severity and risk factors for OAC-associated ICH and the associated implications for using DOACs in AF patients. We also provide an overview of the management of OAC-associated ICH and treatment reversal strategies, including specific and nonspecific reversal agents as well as a comprehensive summary of the evidence about the resumption of DOAC and the optimal timing. EXPERT OPINION: In the setting of an ICH, supportive care/measures are needed, and reversal of anticoagulation with specific agents (including administration of vitamin K, prothrombin complex concentrates, idarucizumab and andexanet alfa) should be considered. Most patients will likely benefit from restarting anticoagulation after an ICH and permanently withdrawn of OAC is associated with worse clinical outcomes. Although the timing of OAC resumption is still under debate, reintroduction after 4-8 weeks of the bleeding event may be possible, after a multidisciplinary approach to decision-making.

Neuroprotection Care Bundle Implementation to Decrease Acute Brain Injury in Preterm Infants.

BACKGROUND: We assessed the impact of an evidence-based neuroprotection care bundle on the risk of brain injury in extremely preterm infants. METHODS: We implemented a neuroprotection care bundle consisting of a combination of neuroprotection interventions such as minimal handling, midline head position, deferred cord clamping, and protocolization of hemodynamic and respiratory managements. These interventions targeted risk factors for acute brain injury in extremely preterm infants (born at gestational age less than 29 weeks) during the first three days of birth. Implementation occurred in a stepwise manner, including care bundle development by a multidisciplinary care team based on previous evidence and experience, standardization of outcome assessment tools, and education. We compared the incidence of the composite outcome of acute preterm brain injury or death preimplementation and postimplementation. RESULTS: Neuroprotection care bundle implementation associated with a significant reduction in acute brain injury risk factors such as the use of inotropes (24% before, 7% after, P value < 0.001) and fluid boluses (37% before, 19% after, P value < 0.001), pneumothorax (5% before, 2% after, P value = 0.002), and opioid use (19% before, 7% after, P value < 0.001). Adjusting for confounding factors, the neuroprotection care bundle significantly reduced death or severe brain injury (adjusted odds ratio, 0.34; 95% confidence interval, 0.20 to 0.59; P value < 0.001) and severe brain injury (adjusted odds ratio, 0.31; 95% confidence interval, 0.17 to 0.58; P < 0.001). CONCLUSIONS: Implementation of neuroprotection care bundle targeting predefined risk factors is feasible and effective in reducing acute brain injury in extremely preterm infants.

Comparative study of intravenous thrombolysis with rt-PA and urokinase for patients with acute cerebral infarction.

OBJECTIVE: Cerebral infarction has a poor prognosis and causes a serious burden on families and society. Recombinant tissue plasminogen activator (rt-PA) and urokinase (UK) are commonly used thrombolytic agents in the clinic. However, direct and powerful clinical trial evidence to determine the therapeutic effect of rt-PA and UK on intravenous thrombolysis is lacking. METHODS: In this study, 180 patients with acute cerebral infarction were treated with rt-PA or UK. The National Institutes of Health Stroke Scale (NIHSS) scores, Barthel index, bleeding complications, and biomarkers were evaluated. RESULTS: No significant differences in NIHSS or Barthel scores were found between the groups. However, UK increased the risk of intracranial haemorrhage compared with rt-PA. rt-PA had increased activity in reducing serum levels of MMP-9 than UK. CONCLUSION: Intravenous thrombolysis with rt-PA and UK in the time window of acute cerebral infarction can achieve similar therapeutic effects, but rt-PA can further reduce the risk of cerebral haemorrhage and is relatively safer than UK.