Thyrolinguofacial trunk arising from the common carotid artery and diagnosed by computed tomography angiography.

PURPOSE: Various variations in the head and neck vasculature have been reported. The purpose of this report is to describe an extremely rare case of thyrolinguofacial trunk (TLFT) arising from the common carotid artery (CCA). METHODS: A 66-year-old woman with vertigo, dizziness, and heaviness in the head underwent computed tomography (CT) angiography of the neck and head region for evaluation of cerebrovascular diseases. RESULTS: The TLFT originated from the anterior wall of the right CCA and was divided into the superior thyroid artery and linguofacial trunk (LFT). The LFT was divided into lingual and facial arteries. In addition, we observed fusiform dilatation of the intracranial right vertebral artery, which might have caused these symptoms. CONCLUSION: The presence of a common trunk of the external carotid artery (ECA) branches increases the risk of complications such as bleeding and ischemia during treatment of the head and neck region, including chemoradiotherapy for oral bleeding and tongue cancer. Therefore, this is an area of significant interest across various medical specialties, including surgery, otolaryngology, and radiology. Understanding the diverse variations in the neck vasculature is expected to lead to a reduction in complications associated with various procedures.

High brain natriuretic peptide level is associated with severe stroke in patients taking oral anticoagulants: A sub-analysis of the PASTA registry study.

BACKGROUND: Brain natriuretic peptides (BNP) are an important diagnostic and prognostic marker in patients with heart failure. However, the relationship between BNP levels and stroke severity in patients with atrial fibrillation (AF) remains unelucidated. In this study, we aimed to investigate the association between stroke severity at admission and BNP levels. METHODS: In this prospective observational study, we used data from 513 patients with AF and acute ischemic stroke treated with oral anticoagulants (OAC) registered in the Multicenter Prospective Analysis of Stroke Patients Taking Oral Anticoagulants study. The patients were divided into two groups: high-BNP (≥200 pg/mL) and low-BNP level (<200 pg/mL) groups. We compared the clinical characteristics between the two groups and determined the effect of BNP levels on stroke severity on admission. RESULTS: Among the 513 enrolled patients, 248 (females, n = 30; median age, 82 years) and 265 (females, n = 76; median age, 71 years) were assigned to the high- and low-BNP level groups, respectively. The high-BNP level group had a higher proportion of patients with severe stroke (National Institutes of Health Stroke Scale score, ≥10) on admission (49.2% vs. 32.8%, p = 0.002) and major vessel occlusion (57.5% vs. 39.2%, p < 0.0001) than that had by the low-BNP level group. Multivariate analysis showed that high BNP level was independently associated with severe stroke on admission (odds ratio 1.07, 95% confidence interval 1.00-1.15; p = 0.0478). CONCLUSIONS: High BNP level compared with low BNP level was associated with severe stroke and major vessel occlusion, even before OAC treatment.

High pre-stroke CHADS2 score predicts unfavorable functional outcome in acute cardioembolic stroke patients prescribed oral anticoagulant therapy: A sub-analysis of the PASTA registry study.

BACKGROUND AND PURPOSE: The impact of CHADS2 score on outcome in patients with stroke taking an oral anticoagulant (OAC) has not yet been fully elucidated. We investigated the association between pre-stroke CHADS2 score and outcome at discharge in patients with acute cardioembolic (CE) stroke due to atrial fibrillation (AF) who were prescribed OAC. METHODS: The data of 548 OAC-treated patients with AF and CE stroke who were registered in the multicenter Prospective Analysis of Stroke patients Taking oral Anticoagulants (PASTA) study were analyzed. High CHADS2 score was defined as a pre-stroke CHADS2 score ≥2. Unfavorable outcome was defined as a modified Rankin scale (mRS) of 3-6. The impacts of pre-stroke CHADS2 score on outcome at discharge were evaluated using multiple logistic regression analysis. RESULT: A high CHADS2 score was found in 472/548 patients and unfavorable outcome was found in 330/548 patients. In patients with unfavorable outcome, age, male sex, pre-stroke CHADS2 score, initial National Institute Health Stroke Scale (NIHSS) score, and glucose level on admission were significantly higher, whereas creatinine clearance and body weight were significantly lower, than those with favorable outcome (each p < 0.001). Multivariate logistic regression analysis indicated that high CHADS2 score (OR 2.18, 95 %CI 1.08-4.42, p = 0.031), pre-stroke mRS (OR 2.21, 95 %CI 1.69-2.67, p < 0.001), and initial NIHSS score (OR 1.19, 95 %CI 1.17-1.24, p < 0.001) were independently associated with unfavorable outcome. CONCLUSION: Pre-stroke CHADS2 score was associated with poor outcome in patients with cardioembolic stroke due to AF, even in those taking OAC.

Prevalence and outcome of pre-onset frailty in patients with acute stroke.

BACKGROUND: Frailty in older individuals is an underappreciated condition that affects the incidence and/or prognosis of stroke. OBJECTIVES: We evaluated the prevalence of pre-onset frailty in patients with acute first-onset and recurrent strokes and association between pre-onset frailty and functional disability at hospital discharge. METHODS: This prospective cohort study included 210 acute stroke patients admitted to the Stroke Unit of Nippon Medical School Hospital during November 2021-June 2022. The mean participant age was 79.2 ± 7.4 years. Age, sex, pre-onset frailty, body mass index (BMI), stroke type, medical history, and National Institutes of Health Stroke Scale (NIHSS) score at admission were evaluated. Frailty was defined as a clinical frailty scale (CFS) score ≥ 5. Frailty prevalence was calculated for all patients, and scores of functional disabilities at discharge were evaluated using modified Rankin scale. RESULTS: Overall frailty prevalence was 31% in all stroke patients, with 24% and 47% of first-onset and recurrent strokes, respectively. Pre-onset frailty, NIHSS score at admission, age, stroke type, previous stroke, sex, BMI, dyslipidemia, and atrial fibrillation were significantly associated with functional disability at discharge. Logistic regression analysis revealed that CFS score, NIHSS score at admission, and previous stroke were independent predictors of functional disability at discharge. CONCLUSIONS: Approximately one-fourth of patients with first-onset stroke had pre-onset frailty; the rate doubled in recurrent stroke; these rates appear to be much larger than rate in healthy individuals. Pre-onset frailty, a negative independent factor affecting functional disability at discharge, is important for pre-onset frailty evaluation and rehabilitation intervention in acute stroke patients.

Endovascular treatment of postoperative hemorrhage after pancreatectomy: a retrospective study.

BACKGROUND: Ruptured aneurysm is a serious complication of distal pancreatectomy (DP) or pancreatoduodenectomy (PD) that can be life-threatening if not treated promptly. This study aimed to examine the efficacy of a Viabahn stent graft for stopping bleeding after pancreatectomy. METHODS: Between April 2016 and June 2022, we performed 245 pancreatectomies in our institution. Six patients experienced postoperative bleeding and underwent endovascular treatment. RESULTS: All six cases of bleeding occurred post-PD (3.7%). The bleeding was from gastroduodenal artery (GDA) pseudoaneurysms in three patients, and Viabahn stent grafts were inserted. All three patients did not show liver function abnormalities or hepatic blood flow disorders. One patient with a Viabahn stent graft experienced rebleeding, which required further management to obtain hemostasis. Of the six cases in which there was hemorrhage, one case of bleeding from the native hepatic artery could not be managed. CONCLUSIONS: Using the Viabahn stent graft is an effective treatment option for postoperative bleeding from GDA pseudoaneurysms following PD. In most cases, using this device resulted in successful hemostasis, without observed abnormalities in hepatic function or blood flow.

Resumption of oral anticoagulation in patients with non-valvular atrial fibrillation after intracerebral hemorrhage: A sub-analysis of the PASTA registry study.

PURPOSE: To investigate the rate and timing of oral anticoagulant (OAC) resumption and its safety in patients after intracerebral hemorrhage (ICH) in current clinical practice in Japan. METHODS: We conducted a sub-analysis of the PASTA registry, an observational, multicenter registry of 1043 patients with stroke receiving OACs in Japan, by including patients with ICH on OAC treatment for non-valvular atrial fibrillation (NVAF). The clinical characteristics of the patients in the resumption and non-resumption groups, rate and timing of OAC resumption, its safety, and switching of OACs after ICH were investigated. RESULTS: Of the 160 patients (women, n = 52; median age, 77 years) included, OACs were resumed in 108 (68%) at a median of 7 days (interquartile range, 4-11) after acute ICH onset. The non-resumption group had higher rates of hematoma expansion (21.2% vs. 7.4%; P = 0.0118) and modified Rankin Scale (mRS) scores at discharge (4 (Suda et al., 2019; Steiner et al., 2014 [3, 4]) vs. 4 (Suda et al., 2019; Steiner et al., 2014; Pasquini et al., 2014 [3-5]); P = 0.0302}. The resumption rate in the mRS 0-4 group was higher than that in the mRS 5 group (75.2% vs. 46.5%; P = 0.00006). The number of days to resumption after ICH onset was longer in the mRS 5 than that in the mRS 0-4 group (median 12 days vs. 7 days, P = 0.0065). There were no significant differences in new-onset ICH, symptomatic hematoma expansion, or gastrointestinal bleeding between groups (P > 0.05). CONCLUSIONS: Early resumption of OAC for NVAF in patients after ICH appeared to be safe. Expected functional outcomes at discharge were associated with OAC resumption and with the timing of resumption. REGISTRATION: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034958.

Regular pulse checks for patients with non-cardioembolic stroke in rehabilitation hospitals to improve recognition and detection of atrial fibrillation (the ESCORT study): protocol for a prospective multicenter observational study.

Background: Cryptogenic stroke (CS) are heterogeneous in origin; however, most CS are embolic mechanism. Paroxysmal atrial fibrillation (AF) is suspected to be a major type of CS that leads to severe cerebral infarction without anticoagulant use. Therefore, the identification of AF is vital in patients with CS. However, patients are often unaware of AF because they have no symptoms, and AF may not be detected on an electrocardiogram (ECG) or Holter ECG on admission. After patients with stroke are treated in the acute phase, they are promptly transferred to a rehabilitation hospital for functional recovery. Once the patient is transferred to a hospital, a few attempts are made to detect AF. In addition, rehabilitation therapists are considered to have insufficient awareness of the possibility of undiagnosed AF. Objective: This study aimed to increase the understanding of the importance of AF detection in patients with ischemic stroke among therapists in rehabilitation hospitals and to investigate whether regular pulse screening can aid in the detection of AF. If AF was detected, we determined the rate and timing of AF detection and identified the patient characteristics. Methods: This multicenter prospective observational study aimed to detect AF in patients with non-cardiac stroke at rehabilitation hospitals. Therapists performed pulse checks before, during, and after rehabilitation. If arrhythmia or tachycardia was detected, an ECG was performed, and the physician checked for AF. If the patient complained of chest symptoms, electrocardiography (ECG) was performed to check for AF. We investigated the characteristics, laboratory data, cognitive status, complications, such as stroke recurrence, and functional outcomes of patients with AF. Results: The study is in the enrollment phase. Recruitment began in September 2022 and will end in August 2023. Patients have provided written informed consent. The main results have been submitted for publication in your journal. Conclusion: The findings of this study will help identify patients with AF in rehabilitation hospitals and improve awareness among therapists.

iPSC-derived mesenchymal stem cells attenuate cerebral ischemia-reperfusion injury by inhibiting inflammatory signaling and oxidative stress.

Induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs) hold great promise as a cell source for transplantation into injured tissues to alleviate inflammation. However, the therapeutic efficacy of iMSC transplantation for ischemic stroke remains unknown. In this study, we evaluated the therapeutic effects of iMSC transplantation on brain injury after ischemia-reperfusion using a rat transient middle cerebral artery occlusion model and compared its therapeutic efficacy with that of bone marrow mesenchymal stem cells (BMMSCs). We showed that iMSCs and BMMSCs reduced infarct volumes after reperfusion and significantly improved motor function on days 3, 7, 14, 28, and 56 and cognitive function on days 28 and 56 after reperfusion compared with the vehicle group. Furthermore, immunological analyses revealed that transplantation of iMSCs and BMMSCs inhibited microglial activation and expression of proinflammatory cytokines and suppressed oxidative stress and neuronal cell death in the cerebral cortex at the ischemic border zone. No difference in therapeutic effect was observed between the iMSC and BMMSC groups. Taken together, our results demonstrate that iMSC therapy can be a practical alternative as a cell source for attenuation of brain injury and improvement of neurological function because of the unlimited supply of uniform therapeutic cells.

Recurrent Stroke with Rapid Development of Intracranial Artery Stenosis and Subsequent Successful Mechanical Thrombectomy in Essential Thrombocythemia.

Essential thrombocythemia is a myeloproliferative neoplasm. Ischemic stroke is frequently the first manifestation of essential thrombocythemia. We herein report a patient with JAK2V617 mutation-positive essential thrombocythemia who developed recurrent ischemic stroke with rapid development of intracranial artery stenosis and subsequently underwent successful mechanical thrombectomy. The high JAK2V617F allele burden in our patient (58.4%) may have affected the patient's condition. We discuss similar reports in the literature and the possible pathophysiologic mechanism of large artery involvement in these patients.

Vitamin K antagonists but not non-vitamin K antagonists in addition on antiplatelet therapy should be associated with increase of hematoma volume and mortality in patients with intracerebral hemorrhage: A sub-analysis of PASTA registry study.

BACKGROUND AND PURPOSE: Prior concomitant use of vitamin K antagonists (VKAs) and antiplatelet (AP) therapy increase the hematoma volume and mortality compared with VKA monotherapy in patients with intracranial hemorrhage (ICH). However, the prior concomitant use of non-vitamin K oral antagonists (NOACs) and AP has not been clarified. METHODS: We conducted a PASTA registry study, which was an observational, multicenter, registry of 1043 patients with stroke receiving oral anticoagulants (OACs) in Japan. In the present study, ICH from the PASTA registry was used to analyze the clinical characteristics including mortality among the four groups (NOAC, VKA, NOAC and AP, and VKA and AP) using univariate and multivariate analyses. RESULTS: Among the 216 patients with ICH, 118 (54.6%), 27 (12.5%), 55 (25.5%), 16 (7.4%) were taking NOAC monotherapy, NOAC and AP, VKA, and VKA and AP, respectively. In-hospital mortality rates were the highest in VKA and AP (31.3%) than in NOACs (11.9%), NOACs and AP (7.4%), and VKA (7.3%). Multivariate logistic regression analysis demonstrated that the concomitant use of VKA and AP (odds ratio [OR], 20.57; 95% confidence interval [CI], 1.75-241.75, p = 0.0162), initial National Institutes of Health Stroke Scale score (OR, 1.21; 95%CI, 1.10-1.37, p < 0.0001), hematoma volume (OR, 1.41; 95%CI, 1.10-1.90, p = 0.066), and systolic blood pressure (OR, 1.31; 95%CI, 1.00-1.75, p = 0.0422) were independently associated with in-hospital mortality. CONCLUSIONS: Although VKA in addition to AP therapy could increase the in-hospital mortality, NOAC and AP did not increase the hematoma volume, stroke severity, or mortality compared to NOAC monotherapy.

Safety of recanalization therapy in patients with acute ischemic stroke on direct oral anticoagulants: A sub-analysis of PASTA registry study.

BACKGROUND: The safety of intravenous recombinant tissue plasminogen activator (rtPA) and mechanical thrombectomy (MT) in patients treated with direct oral anticoagulants (DOACs) before stroke has not been fully investigated. Therefore, we aimed to investigate the safety of recanalization therapy in patients receiving DOACs. METHODS: We assessed data from a prospective multicenter registry of patients with stroke, including those with acute ischemic stroke (AIS) treated with rtPA and/or MT who were administered DOACs. We evaluated the safety of recanalization considering the DOACs dosage and interval between the last DOAC intake and recanalization. RESULTS: The final analysis included 108 patients (women, n = 54; median age, 81 years; DOAC overdose, n = 7; appropriate dose, n = 74; and inappropriate low dose, n = 27). The rate of any ICH differed significantly among overdose-, appropriate dose-, and inappropriate-low dose DOACs groups (71.4, 23.0, and 33.3%, respectively; P = 0.0121), whereas no significant difference was observed in respect of symptomatic ICH (P = 0.6895). Multivariate analysis showed that the National Institutes of Health Stroke Scale score on admission (odds ratio [OR]: 1.06, 95% confidence interval [CI]: 1.01-1.11; P = 0.0267) and overdose-DOAC (OR: 8.40, 95% CI: 1.24-56.88; P = 0.0291) were independently associated with any ICH. No relationship was observed between the timing of the last DOAC intake and occurrence of ICH in patients treated with rtPA and/or MT (all P > 0.05). CONCLUSION: Recanalization therapy during DOAC treatment may be safe in selected patients with AIS, if it is performed >4 h after the last DOAC intake and the patient is not overdosed with DOACs. REGISTRATION: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034958.

Detection of Atrial Fibrillation Using Insertable Cardiac Monitors in Patients With Cryptogenic Stroke in Japan (the LOOK Study): Protocol for a Prospective Multicenter Observational Study.

BACKGROUND: Paroxysmal atrial fibrillation (AF) is a probable cause of cryptogenic stroke (CS), and its detection and treatment are important for the secondary prevention of stroke. Insertable cardiac monitors (ICMs) are clinically effective in screening for AF and are superior to conventional short-term cardiac monitoring. Japanese guidelines for determining clinical indications for ICMs in CS are stricter than those in Western countries. Differences between Japanese and Western guidelines may impact the detection rate and prediction of AF via ICMs in patients with CS. Available data on Japanese patients are limited to small retrospective studies. Furthermore, additional information about AF detection, including the number of episodes, cumulative episode duration, anticoagulation initiation (type and dose of regimen and time of initiation), rate of catheter ablation, role of atrial cardiomyopathy, and stroke recurrence (time of recurrence and cause of the recurrent event), was not provided in the vast majority of previously published studies. OBJECTIVE: In this study, we aim to identify the proportion and timing of AF detection and risk stratification criteria in patients with CS in real-world settings in Japan. METHODS: This is a multicenter, prospective, observational study that aims to use ICMs to evaluate the proportion, timing, and characteristics of AF detection in patients diagnosed with CS. We will investigate the first detection of AF within the initial 6, 12, and 24 months of follow-up after ICM implantation. Patient characteristics, laboratory data, atrial cardiomyopathy markers, serial magnetic resonance imaging findings at baseline, 6, 12, and 24 months after ICM implantation, electrocardiogram readings, transesophageal echocardiography findings, cognitive status, stroke recurrence, and functional outcomes will be compared between patients with AF and patients without AF. Furthermore, we will obtain additional information regarding the number of AF episodes, duration of cumulative AF episodes, and time of anticoagulation initiation. RESULTS: Study recruitment began in February 2020, and thus far, 213 patients have provided written informed consent and are currently in the follow-up phase. The last recruited participant (May 2021) will have completed the 24-month follow-up in May 2023. The main results are expected to be submitted for publication in 2023. CONCLUSIONS: The findings of this study will help identify AF markers and generate a risk scoring system with a novel and superior screening algorithm for occult AF detection while identifying candidates for ICM implantation and aiding the development of diagnostic criteria for CS in Japan. TRIAL REGISTRATION: UMIN Clinical Trial Registry UMIN000039809; https://tinyurl.com/3jaewe6a. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/39307.

Comparative analysis of different response criteria at early phase after PD-1 blockade in non-small lung cancer.

PURPOSE: To compare different response criteria using computed tomography (CT) and positron emission tomography (PET) in measuring response and survival in the early phase after programmed death-1 (PD-1) blockade monotherapy in patients with advanced non-small cell lung cancer (NSCLC). METHODS: A total of 54 patients with advanced NSCLC who had 2-deoxy-2-[fluorine-18]-fluoro-D-glucose PET or CT at baseline, and 4 and 9 weeks after PD-1 blockade, were registered. Therapeutic response was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST), the immune-modified RECIST (irRECIST), the PET Response Criteria in Solid Tumors (PERCIST), the immune-modified PERCIST (iPERCIST), and the European Organization for Research and Treatment of Cancer (EORTC) criteria for dichotomous groups, such as responders vs. non-responders and controlled vs. uncontrolled diseases. Cohen's κ was used to evaluate the concordance among the different criteria. RESULTS: The concordance between CT and PET response criteria was fair or slight for responders vs. non-responders, but the agreement between iPERCIST and irRECIST was moderate for controlled vs. uncontrolled diseases. The agreement between EORTC and PERCIST or iPERCIST in detecting responders was higher in the application of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) than in the standardized uptake value corrected for lean body mass (SUL)peak. To distinguish controlled from uncontrolled disease, RECIST, irRECIST, and PET criteria (PERCIST, iPERCIST, and EORTC) defined by MTV or TLG were found to be significant predictors of progression-free survival. To distinguish responders from non-responders, iPERCIST by SULpeak or EORTC by TLG were identified as significant indicators. The EORTC criteria using TLG for the detection of responders or uncontrolled diseases had a significantly higher predictive value for response assessment. CONCLUSIONS: The EORTC criteria based on TLG for the early detection of responders and uncontrolled disease were effective as a response assessment at 4 weeks after the PD-1 blockade. When SULpeak was not used but MTV or TLG was, the agreement between EORTC and PERCIST or iPERCIST was almost perfect.

Association between Living Conditions and the Risk Factors, Etiology, and Outcome of Ischemic Stroke in Young Adults.

Objective In recent decades, living conditions have changed drastically. However, there are few data regarding the interaction between living conditions and the risk of ischemic stroke (IS) in young adults. The present study explored the association between living conditions or marital status and the risk factors, etiology, and outcome of IS in young adults. Methods We prospectively enrolled patients with incident IS who were 20-49 years old from 37 clinical stroke centers. We collected the demographic data, living conditions, marital status, vascular risk factors, disease etiology, treatment, and outcomes at discharge. A comparison group was established using the official statistics of Japan. We categorized patients into the two groups based on living conditions: solitary group and cohabiting group. Clinical characteristics were then compared between living conditions. Results In total, 303 patients were enrolled (224 men; median age at the onset: 44 years old). Significant factors associated with the incidence of IS were as follows: solitary status, body mass index >30 kg/m2, current smoking, heavy alcohol consumption, hypertension, diabetes mellitus, and dyslipidemia. Furthermore, in the solitary group, the proportions of men, unmarried individuals, and current smokers were significantly higher than in the cohabiting group. In addition, poor outcomes (modified Rankin Scale ≥4) of IS were more common in the solitary group than in the cohabiting group. Conclusion Our study showed that not only conventional vascular risk factors but also living conditions, especially living alone while unmarried, were independent risk factors for IS in young adults.

Prospective assessment using 18F-FDG PET/CT as a novel predictor for early response to PD-1 blockade in non-small-cell lung cancer.

Anti-programmed death-1 (PD-1) blockade is a standard treatment for advanced non-small-cell lung cancer (NSCLC). However, no appropriate modality exists for monitoring its therapeutic response immediately after initiation. Therefore, we aimed to elucidate the clinical relevance of 18F-FDG PET/CT versus CT in predicting the response to PD-1 blockade in the early phase. This prospective study included a total of 54 NSCLC patients. 18F-FDG PET/CT was performed at 4 weeks and 9 weeks after PD-1 blockade monotherapy. Maximum standardized uptake values (SULmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were evaluated. Among all patients, partial metabolic response and progressive metabolic disease after PD-1 blockade were observed in 35.2% and 11.1% on SULmax, 22.2% and 51.8% on MTV, and 27.8% and 46.3% on TLG, respectively, whereas a partial response (PR) and progressive disease (PD), respectively, based on RECIST v1.1 were recognized in 35.2% and 35.2%, respectively. The predictive probability of PR (MTV: 57.9% vs. 21.1%, p = 0.044; TLG: 63.2% vs. 21.1%, p = 0.020) and PD (MTV: 78.9% vs. 47.3%, p = 0.002; TLG: 73.7% vs. 21.1%, p = 0.007) detected based on RECIST at 4 weeks after PD-1 blockade initiation was significantly higher using MTV or TLG on 18F-FDG uptake than on CT. Multivariate analysis revealed that metabolic response by MTV or TLG at 4 weeks was an independent factor for response to PD-1 blockade treatment. Metabolic assessment by MTV or TLG was superior to morphological changes on CT for predicting the therapeutic response and survival at 4 weeks after PD-1 blockade.

Dose length product and outcome of CT fluoroscopy-guided interventions using a new 320-detector row CT scanner with deep-learning reconstruction and new bow-tie filter.

OBJECTIVES: To investigate the dose length product (DLP) and outcomes of CT fluoroscopy (CTF)-guided interventions using a novel 320-detector row CT scanner with deep-learning reconstruction (DLR) and a new bow-tie filter (i.e., Aquilion ONE Prism Edition) and compare with a 320-detector row CT system without DLR and the new bow-tie filter (i.e., Aquilion ONE Vision Edition) (Vision). METHODS: CTF-guided interventions performed using Prism and Vision were retrospectively investigated in terms of the technical success rates, clinical success rates of biopsies, complications, DLPs of total CT scans (total DLPs) from February 2019 to January 2021. The total CT scans included pre-interventional CT scans, CTF scans during the CTF-guided procedure, additional CT scans for additional treatment, CTF scans for additional treatment, and post-interventional CT scans. RESULTS: In this study, 87 and 85 CTF-guided interventions were performed using Vision (Vision group) and Prism (Prism group), respectively. There was no significant difference in the technical success rate (96.6% vs 98.8%, p = 0.621), clinical success rate of biopsies (92.9% vs 93.4%, p = 1.000), and minor (8.0% vs 7.1%, p = 0.807) and major (0% vs 3.5%, p = 0.119) complications between the Prism and Vision groups. The total DLPs for the Prism group were significantly lower than those for the Vision group regardless of the procedure (278 vs 548 mGy*cm, p < 0.001, in the biopsy and 246 vs 667 mGy*cm, p < 0.001, in the drainage and aspiration). CONCLUSIONS: CTF-guided interventions on Prism reduce the total DLP without performance degradation of the intervention. ADVANCES IN KNOWLEDGE: The total DLPs of biopsies and drainages/aspirations in the Prism group decreased by 49 and 63%, respectively.

Randomised placebo-controlled multicentre trial to evaluate the efficacy and safety of JTR-161, allogeneic human dental pulp stem cells, in patients with Acute Ischaemic stRoke (J-REPAIR).

INTRODUCTION: JTR-161 is a novel allogeneic human cell product consisting of dental pulp stem cells isolated from the extracted teeth of healthy adults. It is currently under development as a cell-based therapy for ischaemic stroke. The aim of this study is to evaluate the safety and efficacy of JTR-161 in patients with acute ischaemic stroke when given as a single intravenous administration within 48 hours of symptom onset. METHODS AND ANALYSIS: This is a first-in-human, randomised, double-blind, placebo-controlled, multicentre, phase 1/2 clinical trial to be conducted in Japan (from January 2019 to July 2021). Patients with a clinical diagnosis of anterior circulation ischaemic stroke with a National Institutes of Health Stroke Scale (NIHSS）score of 5-20 at baseline were enrolled. Patients previously treated with recombinant tissue-type plasminogen activator and/or endovascular thrombectomy were allowed to be enrolled. The study consists of three cohorts: cohorts 1 and 2 (each eight patients) and cohort 3 (60 patients). Subjects were randomly assigned to receive either JTR-161 or placebo in a 3:1 ratio in cohorts 1 and 2, and in a 1:1 ratio in cohort 3. The number of cells administered was increased sequentially from 1×108 (cohort 1) to 3 x 108 (cohort 2). In cohort 3, the higher tolerated dose among the two cohorts was administered. The primary endpoint is the proportion of patients who achieve an excellent outcome as defined by all of the following criteria at day 91 in cohort 3: modified Rankin Scale ≤1, NIHSS ≤1 and Barthel Index ≥95. ETHICS AND DISSEMINATION: The protocol and informed consent form were approved by the institutional review board at each participating study site. A manuscript with the results of the primary study will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04608838; JapicCTI-194570 and Clinical Trials. gov.

Dental-Pulp Stem Cells as a Therapeutic Strategy for Ischemic Stroke.

Regenerative medicine aims to restore human functions by regenerating organs and tissues using stem cells or living tissues for the treatment of organ and tissue defects or dysfunction. Clinical trials investigating the treatment of cerebral infarction using mesenchymal stem cells, a type of somatic stem cell therapy, are underway. The development and production of regenerative medicines using somatic stem cells is expected to contribute to the treatment of cerebral infarction, a central nervous system disease for which there is no effective treatment. Numerous experimental studies have shown that cellular therapy, including the use of human dental pulp stem cells, is an attractive strategy for patients with ischemic brain injury. This review describes the basic research, therapeutic mechanism, clinical trials, and future prospects for dental pulp stem cell therapy, which is being investigated in Japan in first-in-human clinical trials for the treatment of patients with acute cerebral ischemia.

Prior direct oral anticoagulant dosage and outcomes in patients with acute ischemic stroke and non-valvular atrial fibrillation: A sub-analysis of PASTA registry study.

BACKGROUND AND PURPOSE: Prescribing under-dose direct oral anticoagulants (DOACs) for non-valvular atrial fibrillation (NVAF) is alerted to increase cardiovascular events or death. However, the association between dose selection of DOACs and the clinical course remains unclear. This study aimed to propose a novel criterion for selecting the DOAC dose and investigate clinical characteristics of ischemic stroke (IS) under this criterion. METHODS: We assessed the pooled prospective multicenter registry data of stroke patients taking anticoagulant agents, including IS patients with NVAF and prior DOAC usage. The recommended dose according to the reduction criteria of each DOAC and the selected dose were identified for each patient, and patients were categorized into four groups: no alternative low-dose, selecting low-dose appropriately with all DOACs applicable for reduction criteria; selected low-dose, selecting low-dose appropriately or inappropriately despite at least one DOAC inapplicable for reduction criteria; selected standard-dose, appropriate standard-dose use; and absolute over-dose, inappropriate standard-dose regardless of criteria. We investigated the effects of dose selection of DOACs on short-term poor functional outcomes. RESULTS: 322 patients were included in the analysis. The prevalence of no alternative low-dose, selected low-dose, selected standard-dose, and absolute over-dose was 74 (23%), 144 (45%), 89 (27%), and 15 (5%), respectively. Multivariable analysis found that the selected low-dose group showed significantly poorer functional outcomes than the selected standard-dose group only in patients without renal dysfunction (OR, 2.60; 95% CI, 1.17-6.00; P = 0.0186). CONCLUSIONS: Selecting a low dose DOAC might be associated with poor functional outcomes in patients without renal dysfunction.

Sustained atrial fibrillation is related to a higher severity of stroke in patients taking direct oral anticoagulants.

BACKGROUND: Atrial fibrillation (AF) includes paroxysmal and sustained (persistent or permanent) AF, and both forms are considered risk factors for ischemic stroke. This study aimed to investigate the differences in stroke severity at admission between patients with paroxysmal AF and sustained AF when treated with direct oral anticoagulants (DOACs). METHODS: Using data from DOAC-treated 300 nonvalvular patients with AF and acute anterior circulation stroke who were registered in the Multicenter Prospective Analysis of Stroke Patients Taking Oral Anticoagulants study, patients were divided into two groups, namely, paroxysmal AF and sustained AF. We compared the clinical characteristics between the two groups and determined the effect of these two types of AF on stroke severity on admission. RESULTS: Of 300 patients, 246 (males, n = 149; median age, 80 years) and 54 (males, n = 32; median age, 78 years) were assigned to the sustained AF and paroxysmal AF groups, respectively. The sustained AF group had a higher proportion of severe stroke (National Institutes of Health Stroke Scale score, >20) on admission (22.0% vs. 5.7%, p = 0.006) and internal carotid artery occlusion (11.4% vs. 1.9%, p = 0.03) compared to the paroxysmal AF group. Multivariate analysis showed that sustained AF was independently associated with severe stroke on admission (odds ratio 4.31, 95% confidence interval 1.24-15.0, p = 0.02). CONCLUSIONS: Sustained AF was associated with a higher severity of stroke accompanied with major vessel occlusion than paroxysmal AF, even prior to DOACs treatment. Registration https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034958.