The Body Mass Index as a Determinant of Acute Ischemic Location in Mild Non-cardioembolic Stroke Patients.

Objective Although the body mass index (BMI) is considered a meaningful parameter for evaluating obesity, the association between the BMI and acute non-cardioembolic stroke remains unclear. We investigated how the BMI was related to patients' background, type of infarction, and infarction location in patients with non-cardioembolic stroke using an acute dual study (ADS) cohort. Methods The ADS trial was conducted between May 2011 and June 2017 in Japan. The BMI classifications were those proposed by the World Health Organization classification: underweight, <18.5 kg/m2; normal weight, 18.5-24.9 kg/m2; overweight, 25-29.9 kg/m2; and obese, ≥30 kg/m2. Results Data from 1136 patients were analyzed. The median BMI was 23.6 kg/m2 (interquartile range: 21.6-25.8 kg/m2), with a BMI ≥30 kg/m2 in 63 patients (6%), 25-29.9 kg/m2 in 321 (28%), 18.5-24.9 kg/m2 in 692 (61%), and <18.5 kg/m2 in 60 (5%). The group with a BMI ≥30 kg/m2 was the youngest, and the group with a BMI <18.5 kg/m2 was the oldest (p<0.001). The proportion of patients with a history of hypertension (p<0.001), diabetes (p<0.001), dyslipidemia (p<0.001), and statin therapy (p=0.005) increased with increasing BMI. Pontine infarcts were frequent in the following order: obese, overweight, normal weight, and underweight (24%, 18%, 14%, and 13%, respectively; p=0.034). In contrast, cortical infarct were frequent in the order of underweight, normal weight, overweight, and obese at 20%, 19%, 14%, and 3%, respectively (p=0.007). Conclusion Acute stroke patients with a high BMI have more atherosclerosis-related factors in their backgrounds than those with lower BMIs. In addition, the BMI may be a determinant of infarct location in patients with acute stroke.

Magnetic Resonance Imaging-Guided Intravenous Thrombolysis in Cardioembolic Stroke Patients With Unknown Time of Onset　- Subanalysis of the THAWS Randomized Control Trial.

BACKGROUND: We investigated the clinical effect of intravenous thrombolysis using a magnetic resonance imaging (MRI)-guided approach in cardioembolic stroke (CE) patients with unknown time of onset.Methods and Results: This subanalysis of the THAWS trial assessed the efficacy and safety of alteplase 0.6 mg/kg in CE patients with unknown time of onset and showing diffusion-weighted imaging-fluid-attenuated inversion recovery mismatch. Patients were classified as CE and non-CE using the SSS-TOAST classification system during the acute period. The efficacy outcome was a modified Rankin Scale score of 0-1 at 90 days. In all, 126 patients from the THAWS trial were included in this study, of whom 45 (35.7%) were diagnosed with CE. In the CE group, a favorable outcome was numerically more frequent in the alteplase than control group (52% vs. 35%; adjusted odds ratio [aOR] 2.25; 95% confidence interval [CI] 0.50-9.99). However, in the non-CE group, favorable outcomes were comparable between the alteplase and control groups (44% vs. 55%, respectively; aOR 0.39; 95% CI 0.12-1.21). Treatment-by-cohort interaction for a favorable outcome was modestly significant between the CE and non-CE groups (P=0.069). In the CE group, no patients experienced symptomatic intracranial hemorrhage (ICH) or parenchymal hematoma Type II following thrombolysis. CONCLUSIONS: When an MRI-guided approach is used, CE patients with unknown time of onset appear to be suitable candidates for thrombolysis.

The effect of asymptomatic intracranial hemorrhage after mechanical thrombectomy on clinical outcome.

BACKGROUND AND OBJECTIVE: Whether asymptomatic intracranial hemorrhage (ICH) affects the clinical outcomes in patients with acute large vessel occlusion treated with mechanical thrombectomy (MT) remains unclear. This study aimed to address this uncertainty. METHODS: We retrospectively analyzed patients with acute ischemic stroke and internal carotid or middle cerebral (M1 segment) artery occlusion treated with MT between April 2011 and March 2021 at a single center. All patients had a premorbid modified Rankin scale (mRS) score ≤ 2 and an anterior circulation occlusion and underwent magnetic resonance imaging at admission. Asymptomatic ICH was defined as ICH without symptomatic ICH defined by the SITS-MOST criteria. A favorable outcome was defined as an mRS score ≤ 2 at 90 days after stroke onset. RESULTS: Our study included 349 patients; 62% were men, the median age was 76 [67-83] years, and the median National Institutes of Health Stroke Scale (NIHSS) score was 15 [8-21]. As determined via computed tomography, 103 (30%) patients had ICH (20 symptomatic and 83 asymptomatic). The favorable outcome rate was significantly lower for asymptomatic vs. no ICH (30% vs. 67%, p < 0.01). In a multivariate regression analysis, a high NIHSS score (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.02-1.10; p < 0.01) and low Alberta Stroke Program Early CT Score (OR, 0.78; 95% CI, 0.65-0.92; p < 0.01) were independent risk factors for ICH. CONCLUSIONS: Asymptomatic ICH is associated with poor clinical outcome at 90 days after stroke onset.

Thrombolysis for Acute Wake-Up and Unclear-Onset Strokes with Alteplase at 0.6 mg/kg in Clinical Practice: THAWS2 Study.

INTRODUCTION: The aim of this study was to determine the safety and efficacy of intravenous (IV) alteplase at 0.6 mg/kg for patients with acute wake-up or unclear-onset strokes in clinical practice. METHODS: This multicenter observational study enrolled acute ischemic stroke patients with last-known-well time >4.5 h who had mismatch between DWI and FLAIR and were treated with IV alteplase. The safety outcomes were symptomatic intracranial hemorrhage (sICH) after thrombolysis, all-cause deaths, and all adverse events. The efficacy outcomes were favorable outcome defined as an mRS score of 0-1 or recovery to the same mRS score as the premorbid score, complete independence defined as an mRS score of 0-1 at 90 days, and change in NIHSS at 24 h from baseline. RESULTS: Sixty-six patients (35 females; mean age, 74 ± 11 years; premorbid complete independence, 54 [82%]; median NIHSS on admission, 11) were enrolled at 15 hospitals. Two patients (3%) had sICH. Median NIHSS changed from 11 (IQR, 6.75-16.25) at baseline to 5 (3-12.25) at 24 h after alteplase initiation (change, -4.8 ± 8.1). At discharge, 31 patients (47%) had favorable outcome and 29 (44%) had complete independence. None died within 90 days. Twenty-three (35%) also underwent mechanical thrombectomy (no sICH, NIHSS change of -8.5 ± 7.3), of whom 11 (48%) were completely independent at discharge. CONCLUSIONS: In real-world clinical practice, IV alteplase for unclear-onset stroke patients with DWI-FLAIR mismatch provided safe and efficacious outcomes comparable to those in previous trials. Additional mechanical thrombectomy was performed safely in them.

Cilostazol addition to aspirin may worsen the short-term outcome in patients with large artery disease: ADS subanalysis.

BACKGROUND: Our previous acute dual study (ADS) reported that dual antiplatelet therapy (DAPT) using cilostazol and aspirin did not reduce the rate of neurological deterioration in non-cardioembolic stroke patients. In this post-hoc analysis, we investigated whether the impact of dual antiplatelet therapy (DAPT) may depend on neurological severity, as represented by large artery disease. METHODS: Neurological deterioration was defined as neurological progression with an increment of the National Institutes of Health Stroke Scale (NIHSS) score of ≥2. NIHSS score subgroups were divided into that of 0-1, 2-4, 5-10, and >10. RESULTS: Among 1014 patients, 203 (20%) had the large artery disease, and 811 (80%) did not. In the total cohort, the rate of neurological deterioration was 10.8% in the DAPT group and 8.3% in the aspirin group (P = 0.197). When we focused on the large artery disease group, DAPT group had a higher rate of neurological deterioration as 18.3% compared to 8.2% in the aspirin group (P = 0.036). Among patients with NIHSS score of 0-1 and 2-4, the rates of neurological deterioration were not different between the two group (both, P = 1.000). However, when NIHSS score elevated to 5-10, 45% in the DAPT group and 9.1% in the aspirin group deteriorated (P = 0.013). Among the patients with NIHSS score of >10, 60% in the DAPT group and none (0%) in the aspirin group had the neurological deterioration (P = 0.045). CONCLUSION: DAPT with aspirin and cilostazol was associated with higher rate of neurological deterioration when patients have large artery disease and not mild neurological deficits.

The impact of SAH finding on CT to the clinical outcome after mechanical thrombectomy for large vessel occlusion.

BACKGROUND AND PURPOSE: Whether subarachnoid haemorrhage (SAH) after mechanical thrombectomy affects the clinical outcomes of patients with acute large-vessel occlusion remains unclear. This study aimed to investigate the clinical impact of SAH on computed tomography (CT) after mechanical thrombectomy. METHODS: The SKIP study was an investigator-initiated, multicentre, randomised, open-label clinical trial. This study was performed in 23 hospital networks in Japan from January 1, 2017, to July 31, 2019. Among the 204 patients, seven were excluded because they did not undergo mechanical thrombectomy (MT) and had a modified Rankin scale (mRS) score > 2. The main outcome was the association between SAH within 36 h after mechanical thrombectomy and the clinical outcome at 90 days. RESULTS: Among 197 patients, the median age was 74 (67-79) years, 62.9% were male. Moreover, 26 (13.2%) patients had SAH (seven isolated SAH) on CT within 36 h. The SAH rate did not differ according to IV rt-PA administration (p = 0.4). The rate of favourable clinical outcomes tended to be lower in patients with SAH rather than patients without SAH (11 [42%] vs. 106 [62%], p = 0.08). Among the seven patients with isolated SAH, 6 showed favourable outcomes at 90 days. In the multivariate regression analysis, the presence of SAH within 36 h from onset was not associated with clinical outcome (Odd ratio, 0.59; 95% confidence interval, 0.18-1.95; p = 0.38). CONCLUSIONS: Among patients with acute stroke treated with MT, SAH, especially isolated SAH findings on CT, were not associated with poor clinical outcomes after 90 days. TRIAL REGISTRATION NUMBER: UMIN000021488.

Ultra-early rt-PA administration should improve patient outcome on mechanical thrombectomy: Post hoc analysis of SKIP.

BACKGROUND: To investigate whether ultra-early recombinant tissue-plasminogen activator (rt-PA) administration can improve patient outcomes on mechanical thrombectomy (MT) in patients with large vessel occlusion (LVO). METHODS: Participants comprised rt-PA-eligible 204 patients with internal carotid artery or middle cerebral artery occlusion in the SKIP trial, who were randomly assigned to receive mechanical thrombectomy alone or combined intravenous thrombolysis (rt-PA: alteplase at 0.6 mg/kg) plus mechanical thrombectomy. We assessed associations between onset-to-puncture time and onset-to-rt-PA administration time and frequency of favorable outcome at 90 days and any intracerebral hemorrhage (ICH) at 36 h after onset. RESULTS: As a cut-off onset-to-puncture time for favorable outcome, receiver operating characteristic curves defined 2.5 h (57% sensitivity, 62% specificity). For onset-to-puncture times ≤2.5 h and > 2.5 h, frequencies of favorable outcomes were 72% and 63% (p = 0.402) in patients with rt-PA therapy and 44% and 58% (p = 0.212) in patients without rt-PA therapy, respectively. In terms of onset-to-rt-PA administration time, frequencies of favorable outcomes among patients with ultra-early rt-PA administration at ≤100, >100 min after onset, and without rt-PA therapy with onset-to-puncture time ≤ 2.5 h, and with and without rt-PA therapy with onset-to-puncture time > 2.5 h were 84% and 64%, 63%, and 44% and 58%, respectively (p = 0.025). Frequencies of any ICH among those patients were 37% and 32%, 32%, and 63% and 40%, respectively (p = 0.006). CONCLUSION: Ultra-early rt-PA administration should improve patient outcomes on mechanical thrombectomy among patients with LVO. Relatively late rt-PA administration might increase the frequency of any ICH.

A differential detailed diffusion-weighted imaging-ASPECTS for cerebral infarct volume measurement and outcome prediction.

BACKGROUND: Diffusion-weighted imaging-Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS) has been used to estimate infarct core volume in acute stroke. However, the same and indiscriminate score deduction for punctate or confluent DWI high-intensity lesion might lead to variation in performance. AIMS: To develop and evaluate a differential detailed DWI-ASPECTS method in comparison with the conventional DWI-ASPECTS in core infarct volume measurement and clinical outcome prediction. METHODS: We retrospectively recruited patients with acute ischemic stroke (AIS) treated with endovascular treatment between April 2013 and October 2019. In differential detailed DWI-ASPECTS, restricted diffusion lesion that was punctate or less than half of a cortical region (M1-M6) would not lead to subtraction of point. A favorable outcome was modified Rankin Scale score ⩽2 at 90 days after stroke onset. RESULTS: Among 298 AIS patients, mean age was 75 years (interquartile range (IQR) 67-82), and 194 patients (65%) were males. Mean infarct core volume was 11 mL (IQR 3-37). Overall, the score by detailed DWI-ASPECTS was significantly higher than conventional DWI-ASPECTS (8 (7-9) vs. 7 (5-9); P < 0.01). The detailed DWI-ASPECTS resulted in a higher correlation coefficient (r) for core infarct volume estimation than the conventional DWI-ASPECTS (r = 0.832 vs. 0.773; P < 0.01). Upon re-classification of those scored ⩽6 in conventional DWI-ASPECTS (n = 134) by detailed DWI-ASPECTS, the rate of favorable outcome in patients with detailed DWI-ASPECTS >6 was significantly higher than those with ⩽6 (29 (48%) vs. 14 (19%); P < 0.01). CONCLUSIONS: Detailed DWI-ASPECTS appeared to provide a more accurate infarct core volume measurement and clinical outcome correlation than conventional DWI-ASPECTS among AIS patients treated with endovascular therapy.

Persistent High Pulse Pressure in Acute Non-Cardiogenic Ischemic Stroke as a Predictor of Neurological Deterioration and Recurrence of Ischemic Stroke: ADS Post-Hoc Analysis.

AIM: Studies investigating the relationship between pulse pressure (PP) and prognosis in acute ischemic stroke remain limited. Thus, in this study, we aim to determine whether changes in PP in the early phase of ischemic stroke are associated with neurological deterioration or stroke recurrence. METHODS: Patients who participated in the Acute Aspirin Plus Cilostazol Dual Therapy for Non-cardiogenic Stroke Patients Within 48 Hours of Symptom Onset (ADS) trial were included in this study. We then divided the patients into four groups (low-low, low-high, high-low, high-high) according to low or high PP both on admission and 24 h after admission. The threshold PP calculated by receiver operating characteristic curve analysis of PP on admission for neurological deterioration within 14 days and recurrent ischemic stroke/transient ischemic attack (TIA) within 3 months was 69 mmHg. RESULTS: Neurological deterioration within 14 days was observed in 118 patients (10.6%), whereas recurrent ischemic stroke/TIA within 3 months was noted in 34 patients (3.2%). Among these four groups, both neurological deterioration within 14 days (odds ratio [OR] 2.09, 95% confidence interval [CI] 1.12-3.91; p=0.0209) and recurrent ischemic stroke/TIA within 3 months (OR 4.80; 95% CI 1.62-14.86; p=0.0064) were significantly more frequent in the high-high group than in the low-low group as per the results of our multivariate analysis. In addition, neurological deterioration within 14 days was significantly higher in the high-low group than that in the low-low group (OR 2.70; 95% CI 1.44-5.05; p=0.0019). CONCLUSIONS: High PP during the acute phase of ischemic stroke appears to be associated with ischemic stroke recurrence and neurological deterioration, particularly if PP is elevated both on admission and 24 h later after admission.

[A case of neurosyphilis presenting as bilateral temporal, cortical and subcortical encephalitis].

A 37-year-old man who had a low grade fever for 5 days admitted to our hospital due to disturbance of consciousness and seizure. Brain MRI showed abnormal hyperintensity in the bilateral temporal lobes, cortical and subcortical lesions on fluid-attenuated inversion recovery image. Treponemal and non-treponemal specific antibodies were positive in serum and cerebrospinal fluid, therefore he was diagnosed as having neurosyphilis. Treatment with intravenous penicillin G and metylpredonisolone improved his clinical symptons, imaging abnormalities and CSF findings. Patients of neurosyphilis with mesiotemporal encephalitis show common features such as young age, HIV-negative, subacute cognitive impairment and seizure, as seen in our case. Early diagnosis of neurosyphilis and appropriate treatment make clinical improvement, however the clinical diagnosis of neurosyphilis is sometime difficult because most patients present with disturbance of consciousness or seizure. The possibility of neurosyphilis should be considered when MRI results indicate temporal abnormalities.

Intravenous Alteplase at 0.6 mg/kg for Unknown Onset Stroke with Prior Antithrombotic Medication: THAWS Randomized Clinical Trial.

AIM: This study aimed to assess the potential effect of prior antithrombotic medication for thrombolysis in an unknown onset stroke. METHODS: This was a predefined sub-analysis of the THAWS trial. Stroke patients with a time last known well ＞4.5 h who had a DWI-fluid-attenuated inversion recovery mismatch were randomly assigned (1:1) to receive alteplase at 0.6 mg/kg (alteplase group) or standard medical treatment (control group). Patients were dichotomized by prior antithrombotic medication. RESULTS: Of 126 patients (intention-to-treat population), 40 took antithrombotic medication (24 with antiplatelets alone, 13 with anticoagulants alone, and 3 with both), and the remaining 86 did not before stroke onset. Of these, 17 and 52 patients, respectively, received alteplase, and 23 and 34, respectively, had standard medical treatment. Antithrombotic therapy was initiated within 24 h after randomization less frequently in the alteplase group (12% vs. 86%, p＜0.01). Both any intracranial hemorrhage within 22-36 h (26% vs. 14%) and a modified Rankin Scale score of 0-1 at 90 days (good outcome) (47% vs. 48%) were comparable between the two groups. A good outcome was more common in the alteplase group than in the control group in patients with prior antithrombotic medication [relative risk (RR) 2.25, 95% confidence interval (CI) 1.02-4.99], but it tended to be less common in the alteplase group in those without (RR 0.69, 95% CI 0.46-1.03) (p＜0.01 for interaction). The frequency of any intracranial hemorrhage did not significantly differ between the two groups in any patients dichotomized by prior antithrombotic medication. CONCLUSION: Alteplase appears more beneficial in patients with prior antithrombotic medication.

Tachycardia Changes Increase Neurological Deterioration in Patients with Acute Non-Cardioembolic Stroke: An ADS Post-Hoc Analysis.

AIM: A previous randomized study showed that dual antiplatelet therapy (DAPT) with aspirin and cilostazol is not superior to aspirin monotherapy for patients with acute non-cardioembolic stroke; however, the reason for this remains uncertain. We focused on the unusual side effects of cilostazol, namely, tachycardia changes, and validated their influence on patients with acute non-cardioembolic stroke. METHODS: This post-hoc study extracted data from the acute aspirin plus cilostazol dual therapy study (ADS) registry, a multicenter, prospective, randomized, open-label trial. Patients were randomly allocated to the dual group (aspirin plus cilostazol) and the aspirin monotherapy group (aspirin alone). Tachycardia changes were defined as ≥ 5% heart rate increase at 48 h after admission compared with that at admission. Baseline data and outcomes were validated with four divided groups: aspirin-non-tachycardia changes (AN), aspirin-tachycardia changes (AT), dual-non-tachycardia changes (DN), and dual-tachycardia changes (DT). RESULTS: Finally, 1,188 patients were analyzed in this ADS post-hoc analysis (aspirin monotherapy group, 594; dual group, 594). The proportion of change in tachycardia was 19.2% in the aspirin monotherapy group and 38.2% in the dual group (p＜0.001＊＊＊). Although the recurrences of symptomatic stroke and transient ischemic attack were not significantly different, the neurological deterioration was significantly different among the AN, AT, DN, and DT groups (p＜0.05＊). CONCLUSIONS: Tachycardia changes increase neurological deterioration even in patients with non-cardioembolic acute stroke. DAPT consisting of aspirin and cilostazol increases the proportion of tachycardia changes and is not superior to aspirin monotherapy.

National Institutes of Health Stroke Scale Score Less Than 10 at 24 hours After Stroke Onset Is a Strong Predictor of a Favorable Outcome After Mechanical Thrombectomy.

BACKGROUND: There are a few accurate predictors of patient outcomes after mechanical thrombectomy (MT). OBJECTIVE: To investigate whether the National Institutes of Health Stroke Scale (NIHSS) score 24 hours after stroke onset could predict favorable outcomes at 90 days in patients with acute stroke treated with MT. METHODS: Patients from the SKIP study were enrolled in this study. Using receiver operating characteristic curves, the optimal cut-off NIHSS score 24 hours after stroke onset was calculated to distinguish between favorable (modified Rankin Scale score 0-2) and unfavorable (modified Rankin Scale score 3-6) outcomes at 90 days. These receiver operating characteristic curves were compared with those of previously reported predictors of favorable outcomes, such as the ΔNIHSS score (baseline NIHSS score-NIHSS score at 24 h), percent delta (ΔNIHSS score × 100/baseline NIHSS score), and early neurological improvement indices. RESULTS: A total of 177 patients (median age, 72 years; female, 65 [37%]) were enrolled, and 109 (61.9%) had favorable outcomes. The respective sensitivity, specificity, and area under the curve values for an NIHSS of 10 were 92.6%, 80.7%, and .906; a ΔNIHSS score of 7 were 70.6%, 76.1%, and .797; and percent delta of 48.3% were 85.3%, 80.7%, and .890. CONCLUSION: NIHSS score <10 at 24 hours after stroke onset is a strong predictor of favorable outcomes at 90 days in patients treated with MT.

[Delayed white matter lesion after mechanical thrombectomy for middle cerebral artery occlusion with Libman-Sacks endocarditis].

A 59-year-old woman presented with right hemiparesis and was transported from outside hospital. MRI revealed acute infarction and the left middle cerebral artery M2 occlusion. Intravenous infusion of recombinant tissue-type plasminogen activator, and mechanical thrombectomy (MT) were performed. The cause of cerebral infarction was diagnosed as Libman-Sacks endocarditis. She discharged without sequelae. After 10 months later, she presented with mild cognitive decline, and MRI showed new white matter lesion in left deep white matter. In magnetic resonance spectroscopy, the lesion showed an increased rate of choline/creatine, and a decreased rate of N-acetylaspartate/creatine, elevated lactate peak. When new higher brain dysfunction presented after recanalization by MT, it might be related to the delayed white matter lesion.

The safety of rapid administration of enteral nutrition in acute stroke patients.

BACKGROUND/AIMS: Early initiation of enteral nutrition (EN) is recommended for acute stroke patients, but it is time-consuming. Reducing EN administration time without increasing the frequency of complications is a worthwhile goal. We aimed to determine whether this goal was feasible. METHODS: Consecutive acute stroke patients with severe dysphagia within 72 h of hospital admission who received EN were retrospectively enrolled. Patients were classified into two groups (Rapid administration group: 100 mL/5 min on days 1-3 after stroke onset and 200 mL/30 min on days 4-7, Conventional administration group: 100 mL/h on days 1-3 and 200 mL/h on days 4-7). RESULTS: Among 118 consecutive acute stroke patients, 71 patients [median age, 77 (68-82) years; 37 (52%) males] were enrolled. The baseline clinical characteristics of the rapid administration group (45 patients) and the conventional administration group (26 patients) did not differ. The total duration of EN administration in the first week after stroke onset was significantly longer in the conventional vs. rapid administration group [21 (15-21) h vs. 6 (2-8) h, p < 0.01]. There were no significant differences in the frequency of diarrhea (42% vs. 42%, p = 1.00), vomiting (0% vs. 7%, p = 0.29), or pneumonia (15% vs. 7%, p = 0.41). There was also no difference in the percentage of patients with one or more complications (54% vs. 49%, p = 0.81). CONCLUSIONS: Rapid administration of EN is safe and has the potential to decrease the time required for EN feeding.

Direct to angiography suite approaches for the triage of suspected acute stroke patients: a systematic review and meta-analysis.

BACKGROUND: Increasing evidence suggests improved time metrics leading to better clinical outcomes when stroke patients with suspected large vessel occlusion (LVO) are transferred directly to the angiography suite (DTAS) compared with cross-sectional imaging followed by transfer to the angiography suite. We performed a systematic review and meta-analysis on the efficacy and safety of DTAS approaches. METHODS: We searched Embase, Medline, Scopus, and clinicaltrials.gov for studies comparing outcomes of DTAS and conventional triage. Eligible studies were assessed for risk of bias. We performed a random-effects meta-analysis on the differences of median door-to-groin and door-to-reperfusion times between intervention and control group. Secondary outcomes included good outcome at 90 days (modified Rankin Scale ⩽ 2) rate of symptomatic intracranial hemorrhage (sICH) and mortality within 90 days. RESULTS: Eight studies (one randomized, one cluster-randomized trial and six observational studies) with 1938 patients were included. Door-to-groin and door-to-reperfusion times in the intervention group were on median 29.0 min [95% confidence interval (CI): 14.3-43.6; p < 0.001] and 32.1 min (95% CI: 15.1-49.1; p < 0.001) shorter compared with controls. Prespecified subgroup analyses for transfer (n = 1753) and mothership patients (n = 185) showed similar reductions of the door-to-groin and door-to-reperfusion times in response to the intervention. The odds of good outcome did not differ significantly between both groups but were numerically higher in the intervention group (odds ratio: 1.38, 95% CI: 0.97-1.95; p = 0.07). There was no significant difference for mortality and sICH between the groups. CONCLUSION: DTAS approaches for the triage of suspected LVO patients led to a significant reduction in door-to-groin and door-to-reperfusion times but an effect on functional outcome was not detected. The subgroup analysis showed similar results for transfer and mothership patients.Registration: This study was registered in PROSPERO (CRD42020213621).

p53 deficiency promotes bone regeneration by functional regulation of mesenchymal stromal cells and osteoblasts.

INTRODUCTION: The detailed mechanism of the process during bone healing of drill-hole injury has been elucidated, but a crucial factor in regulating drill-hole healing has not been identified. The transcription factor p53 suppresses osteoblast differentiation through inhibition of osterix expression. In present study, we demonstrate the effects of p53 deficiency on the capacity of MSCs and osteoblasts during drill-hole healing. MATERIALS AND METHODS: Mesenchymal stromal cells (MSCs) and osteoblasts were collected from bone marrow and calvaria of p53 knockout (KO) mice, respectively. The activities of cell mobility, cell proliferation, osteoblast differentiation, and wound healing of MSCs and/or osteoblasts were determined by in vitro experiments. In addition, bone healing of drill-hole injury in KO mice was examined by micro-CT and immunohistological analysis using anti-osterix, Runx2, and sclerostin antibodies. RESULTS: KO MSCs stimulated cell mobility, cell proliferation, and osteoblast differentiation. Likewise, KO osteoblasts enhanced cell proliferation and wound healing. KO MSCs and osteoblasts showed high potency in the inflammation and callus formation phases compared to those from wild-type (WT) mice. In addition, increased expression of osterix and Runx2 was observed in KO MSCs and osteoblasts that migrated in the drill-hole. Conversely, sclerostin expression was inhibited in KO mice. Eventually, KO mice exhibited high repairability of drill-hole injury, suggesting a novel role of p53 in MSCs and osteoblasts in improving bone healing. CONCLUSION: p53 Deficiency promotes bone healing of drill-hole injury by enhancing the bone-regenerative ability of MSCs and osteoblasts.

Cerebral microbleeds development after stroke thrombolysis: A secondary analysis of the THAWS randomized clinical trial.

BACKGROUND AND AIM: We determined to investigate the incidence and clinical impact of new cerebral microbleeds after intravenous thrombolysis in patients with acute stroke. METHODS: The THAWS was a multicenter, randomized trial to study the efficacy and safety of intravenous thrombolysis with alteplase in patients with wake-up stroke or unknown onset stroke. Prescheduled T2*-weighted imaging assessed cerebral microbleeds at three time points: baseline, 22-36 h, and 7-14 days. Outcomes included new cerebral microbleeds development, modified Rankin Scale (mRS) ≥3 at 90 days, and change in the National Institutes of Health Stroke Scale (NIHSS) score from 24 h to 7 days. RESULTS: Of all 131 patients randomized in the THAWS trial, 113 patients (mean 74.3 ± 12.6 years, 50 female, 62 allocated to intravenous thrombolysis) were available for analysis. Overall, 46 (41%) had baseline cerebral microbleeds (15 strictly lobar cerebral microbleeds, 14 mixed cerebral microbleeds, and 17 deep cerebral microbleeds). New cerebral microbleeds only emerged in the intravenous thrombolysis group (seven patients, 11%) within a median of 28.3 h, and did not additionally increase within a median of 7.35 days. In adjusted models, number of cerebral microbleeds (relative risk (RR) 1.30, 95% confidence interval (CI): 1.17-1.44), mixed distribution (RR 19.2, 95% CI: 3.94-93.7), and cerebral microbleeds burden ≥5 (RR 44.9, 95% CI: 5.78-349.8) were associated with new cerebral microbleeds. New cerebral microbleeds were associated with an increase in NIHSS score (p = 0.023). Treatment with alteplase in patients with baseline ≥5 cerebral microbleeds resulted in a numerical shift toward worse outcomes on ordinal mRS (median [IQR]; 4 [3-4] vs. 0 [0-3]), compared with those with <5 cerebral microbleeds (common odds ratio 17.1, 95% CI: 0.76-382.8). The association of baseline ≥5 cerebral microbleeds with ordinal mRS score differed according to the treatment group (p interaction = 0.042). CONCLUSION: New cerebral microbleeds developed within 36 h in 11% of the patients after intravenous thrombolysis, and they were significantly associated with mixed-distribution and ≥5 cerebral microbleeds. New cerebral microbleeds development might impede neurological improvement. Furthermore, cerebral microbleeds burden might affect the effect of alteplase.

"Computed Tomography Perihematomal Rims": A Perihematomal Low-Density Area Is a Part of an Acute Brain Hemorrhage.

Objective Computed tomography (CT) can be used for visualizing acute intracerebral hemorrhages (ICHs) as distinct hyperdense areas and cerebral edema as perihematomal low-density areas (LDAs). We observed a perihematomal LDA on CT, which appeared to be part of a hemorrhage on magnetic resonance imaging (MRI) in acute ICH. We named this "CT perihematomal rim" and evaluated its characteristics and clinical significance. Methods We stratified patients with acute ICH according to the presence or absence of a CT perihematomal rim and then compared their radiologic findings. Logistic regression analyses were performed to assess whether the CT findings can predict the presence of a CT perihematomal rim. Patients Patients within 24 hours of ICH onset who were admitted between September 1, 2014, and October 31, 2018, were registered. Results Overall, 139 patients (91 men; mean age, 66 years) were investigated. CT perihematomal rims were observed in 40 patients (29%). ICH volumes on CT were 30% smaller than those on MRI in patients with CT perihematomal rims. On a multivariate analysis, the presence of a CT perihematomal rim was independently associated with the maximum diameter of the perihematomal LDA. According to a receiver operating characteristic analysis, the maximum LDA diameter threshold was 7.5 mm (sensitivity, 85%; specificity, 83%). Conclusion CT perihematomal rims were observed in 29% of the patients with acute ICH. A perihematomal LDA (>7.5 mm) in acute ICH cases should be considered a CT perihematomal rim. Clinicians should be aware that the ICH volume on CT may be underestimated by 30%.

Microbleeds and clinical outcome in acute mild stroke patients treated with antiplatelet therapy: ADS post-hoc analysis.

BACKGROUND AND PURPOSE: In this post-hoc analysis using acute dual study dataset, the impacts of cerebral microbleeds (MBs) after mild stroke on clinical outcome were investigated. METHODS: The number of MBs on admission was categorized as 1) no MBs, 2) MBs 1-4, 3) MBs 5-9, and 4) MBs ≥ 10. The efficacy outcome was defined as neurological deterioration and stroke recurrence within 14 days. Safety outcomes included ICH and/or SAH as well as extracranial hemorrhages. RESULTS: Of the 1102 patients, 780 (71%) had no MBs on admission, while 230 (21%) had MBs 1-4, 48 (4%) had MBs 5-9, and 44 (4%) had MBs ≥ 10. The number of MBs was not associated with the neurological deterioration and/or stroke recurrence (p = 0.934), ICH and/or SAH (p = 0.743), and extracranial hemorrhage (p = 0.205). Favorable outcome was seem in 84% in the No MBs group, 83% in the MBs 1-4, 94% in the MBs 5-9, and 85% in the MBs ≥ 10 (p = 0.304). Combined cilostazol and aspirin therapy did not alter any rates of efficacy and safety outcomes among the no MBs, MBs 1-4, MBs 5-9, and MBs ≥ 10 groups compared to aspirin alone (all p > 0.05). By multivariate regression analysis, a history of ICH and diastolic blood pressure were the independent parameters to all of the MBs criteria (presence, MBs ≥ 5, and MBs ≥ 10). CONCLUSIONS: MBs did not alter the clinical outcome at 3 months of onset. Elevated diastolic blood pressure and a history of ICH were the essential parameters related to the MBs.