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Background: The number of mechanical thrombectomy (MT) for acute ischemic stroke (AIS) in elderly patients has increased, but the feasibility and safety are still debated. We aimed to investigate the risk factors and produce a prognostic scoring system for MT in elderly AIS patients. Methods: We analyzed data from 763 consecutive patients who underwent MT for AIS between January 2013 and January 2020 at seven comprehensive stroke centers for derivation group. We defined elderly patients as ≥ 75 years of age. We investigated the risk factors of MT among these elderly patients and developed a prognostic scoring system assigned weighted points proportional to their standardized coefficient values. We conducted a subsequent validation study that included 287 consecutive patients treated between February 2020 and December 2021. Results: In total, 251 elderly patients in derivation group were analyzed retrospectively. According to the multivariable analysis, we developed a scoring system (SNA 3 P score) consisting of six factors, including age ≥ 90 (2 points), female sex (2 points), a pre-modified Rankin Scale (mRS) score of 2 (1 point), anticoagulant drug use (2 points), the NIHSS score (4 points), and the ASPECTS (4 points). A score ≤ 5 predicted an mRS score of 0-2 at 90 days with a sensitivity of 74% and a specificity of 65%, and the area under the curve (AUC) was 0.76. In the validation study, a score ≤ 5 predicted an mRS score of 0-2 at 90 days with a sensitivity of 70% and a specificity of 60% (AUC was 0.74). Conclusions: We created the novel scoring system to predict the functional outcome of elderly AIS patients undergoing MT. This simple scoring system may provide the information for indication of MT for elderly AIS patients, but further investigation for external validation is needed.

Background and Purpose: The efficacy of mechanical thrombectomy (MT) for posterior circulation large vessel occlusions has not been fully elucidated. We investigated the efficacy and safety of MT for posterior circulation stroke (PCS) compared with anterior circulation stroke (ACS). Methods: We analyzed 885 consecutive patients who underwent MT for acute ischemic stroke between January 2013 and December 2020 at six comprehensive stroke centers. The patients were divided into two groups; the PCS and ACS group. The procedural and clinical outcomes were compared between the groups. Results: A total of 767 patients (PCS group, 83; ACS group, 684), were analyzed. PCS patients were significantly younger (75 vs. 79, P = 0.008) and had a higher NIHSS score at baseline (23 vs 19, p=0.012) and longer door to puncture time (97 vs 73 min, p=0.009). The rate of male (67.0 vs 46.9% p Conclusions: MT for PCS seemed to be beneficial, having similar complication, recanalization rate, and clinical outcomes with ACS.

Background and Purpose: Japan has a rapidly aging population and the application of mechanical thrombectomy (MT) for acute ischemic stroke (AIS) among elderly patients has increased, but feasibility and safety of MT for elderly patients are still debated. Therefore, this study aimed to elucidate feasibility and safety of MT by analyzing the retrospective multicenter database. Methods: A total of 763 consecutive patients who underwent MT for AIS between January 2013 and January 2020 at six comprehensive stroke centers were enrolled in this study. We analyzed elderly AIS patients defined as those aged ≥ 75 years with IC/M1/M2 occlusion. Good outcome was defined mRS 0-2 at 90 days after onset, and we investigated the factors associated with good outcome. Results: A total of 523 patients with IC/M1/M2 occlusion were analyzed, of which 316 were elderly (52%). Good outcome was significantly decreased in elderly AIS patients compared with non-elderly patients (35 % vs 56 %, p=0.0007). Among the elderly AIS patients, aged < 90 years, male sex, NIH stroke scale, prior administration of anticoagulants, mRS before onset, ASPECTS, M2 occlusion, and dyslipidemia were associated with good outcome with multivariable analysis. An elderly AIS prognostic scoring system (eAIS-PSS) was set up based on these factors , and the areas under the curves (AUC) was 0.78 at the optimal cut-off value of 7 / 22 with this scoring system. eAIS-PSS predicted good outcome with a sensitivity of 72% and a specificity of 75%. Conclusion: eAIS-PSS was useful to predict good outcome in MT for elderly AIS patients.

BACKGROUND After the Great East Japan Earthquake in 2011, backup systems for clinical information were launched in Japan. The system in Miyagi Prefecture called the Miyagi Medical and Welfare Information Network (MMWIN) is used as a health information exchange network to share clinical information among various medical facilities for patients who have opted in. Hospitals and clinics specializing in chronic renal failure require patients’ data and records during hemodialysis to facilitate communication in daily clinical activity and preparedness for disasters. OBJECTIVE This study aimed to facilitate the sharing of clinical data of patients undergoing hemodialysis among different hemodialysis facilities. METHODS We introduced a document-sharing system to make hemodialysis reports available on the MMWIN. We also recruited hospitals and clinics to share the hemodialysis reports of their patients and promoted the development of a network between emergency and dialysis clinics. RESULTS In addition to basic patient information as well as information on diagnosis, prescription, laboratory data, hospitalization, allergy, and image data from different facilities, specific information about hemodialysis is available, as well as a backup of indispensable information in preparation for disasters. As of June 1, 2021, 12 clinics and 10 hospitals of 68 dialysis facilities in Miyagi participated in the MMWIN. The number of patients who underwent hemodialysis in Miyagi increased by more than 40%. CONCLUSIONS Our backup system successfully developed a network of hemodialysis facilities. We have accumulated data that are beneficial to prevent the fragmentation of patient information and would be helpful in transferring patients efficiently during unpredictable disasters.

Background After the Great East Japan Earthquake in 2011, backup systems for clinical information were launched in Japan. The system in Miyagi Prefecture called the Miyagi Medical and Welfare Information Network (MMWIN) is used as a health information exchange network to share clinical information among various medical facilities for patients who have opted in. Hospitals and clinics specializing in chronic renal failure require patients’ data and records during hemodialysis to facilitate communication in daily clinical activity and preparedness for disasters. Objective This study aimed to facilitate the sharing of clinical data of patients undergoing hemodialysis among different hemodialysis facilities. Methods We introduced a document-sharing system to make hemodialysis reports available on the MMWIN. We also recruited hospitals and clinics to share the hemodialysis reports of their patients and promoted the development of a network between emergency and dialysis clinics. Results In addition to basic patient information as well as information on diagnosis, prescription, laboratory data, hospitalization, allergy, and image data from different facilities, specific information about hemodialysis is available, as well as a backup of indispensable information in preparation for disasters. As of June 1, 2021, 12 clinics and 10 hospitals of 68 dialysis facilities in Miyagi participated in the MMWIN. The number of patients who underwent hemodialysis in Miyagi increased by more than 40%. Conclusions Our backup system successfully developed a network of hemodialysis facilities. We have accumulated data that are beneficial to prevent the fragmentation of patient information and would be helpful in transferring patients efficiently during unpredictable disasters.

To elucidate the differences in ocular biometric parameters by generation and gender and to identify axial length (AL)-associated genetic variants in Japanese individuals, we analyzed Tohoku Medical Megabank Organization (ToMMo) Eye Study data.We designed the ToMMo Eye Study, examined AL variations, and conducted genome-wide association studies (GWASs).In total, 33 483 participants aged18 years who were recruited into the community-based cohort (CommCohort) and the birth and three-generation cohort (BirThree Cohort) of the ToMMo Eye Study were examined.Each participant was screened with an interview, ophthalmic examinations, and a microarray analysis. The GWASs were performed in 22 379 participants in the CommCohort (discovery stage) and 11 104 participants in the BirThree Cohort (replication stage). We evaluated the associations of single nucleotide polymorphisms (SNPs) with AL using a genome-wide significance threshold (5 × 10We identified the association of SNPs with AL and distributions of AL in right and left eyes and individuals of different sexes and ages.In the discovery stage, the mean AL of the right eye (23.99 mm) was significantly greater than that of the left eye (23.95 mm). This difference was reproducible across sexes and ages. The GWASs revealed 703 and 215 AL-associated SNPs with genome-wide significance in the discovery and validation stages, respectively, and many of the SNPs in the discovery stage were replicated in the validation stage. Validated SNPs and their associated loci were meta-analyzed for statistical significance (Our large-scale GWASs exploiting ToMMo Eye Study data identified 31 loci linked to variations in AL, 7 of which are newly reported in this article. The results revealed genetic heterogeneity and similarity in SNPs related to ethnic variations in AL.

On March 11, 2011, the Great East Japan Earthquake and ensuing tsunami that hit the northeastern coastal region of Japan caused about 18,000 casualties and destroyed numerous buildings. Additionally, many medical facilities were damaged and patient medical records lost. In order to maintain patient clinical information, a prefectural medical network system, the Miyagi Medical and Welfare Information Network (MMWIN), began providing backup data storage services in 2013 for hospitals, clinics, pharmacies, and other care facilities as a precaution for upcoming disasters. This system also facilitates the sharing of clinical information trans-institutionally as long as patients provide consent for this. In the present study, we examined the development of the MMWIN and its efficiency during the 5 years from its launch, and identified general problems to maintain such a backup system. At the end of 2018, the system contained backup data from more than 11 million patients with more than 420 million data items; more than 900 facilities were MMWIN users, and the number of patients consenting to sharing their clinical information reached 90,000. The use of the system has become widespread and the accumulating data should be utilized for research in the future. Maintaining a balance between income and cost is critical to make this project independent from local government subsidies.

ObjectivesThis cross-sectional survey explored the characteristics and outcomes of direct oral anticoagulant (DOAC)–associated nontraumatic intracerebral hemorrhages (ICHs) by analyzing a large nationwide Japanese discharge database.MethodsWe analyzed data from 2,245 patients who experienced ICHs while taking anticoagulants (DOAC: 227; warfarin: 2,018) and were urgently hospitalized at 621 institutions in Japan between April 2010 and March 2015. We compared the DOAC- and warfarin-treated patients based on their backgrounds, ICH severities, antiplatelet therapies at admission, hematoma removal surgeries, reversal agents, mortality rates, and modified Rankin Scale scores at discharge.ResultsDOAC-associated ICHs were less likely to cause moderately or severely impaired consciousness (DOAC-associated ICHs: 31.3%; warfarin-associated ICHs: 39.4%; p = 0.002) or require surgical removal (DOAC-associated ICHs: 5.3%; warfarin-associated ICHs: 9.9%; p = 0.024) in the univariate analysis. Propensity score analysis revealed that patients with DOAC-associated ICHs also exhibited lower mortality rates within 1 day (odds ratio [OR] 4.96, p = 0.005), within 7 days (OR 2.29, p = 0.037), and during hospitalization (OR 1.96, p = 0.039).ConclusionsThis nationwide study revealed that DOAC-treated patients had less severe ICHs and lower mortality rates than did warfarin-treated patients, probably due to milder hemorrhages at admission and lower hematoma expansion frequencies.

Background We aimed to develop quality indicators (QIs) related to primary and comprehensive stroke care and examine the feasibility of their measurement using the existing Diagnosis Procedure Combination (DPC) database. Methods and results We conducted a systematic review of domestic and international studies using the modified Delphi method. Feasibility of measuring the QI adherence rates was examined using a DPC-based nationwide stroke database (396,350 patients admitted during 2013-2015 to 558 hospitals participating in the J-ASPECT study). Associations between adherence rates of these QIs and hospital characteristics were analyzed using hierarchical logistic regression analysis. We developed 17 and 12 measures as QIs for primary and comprehensive stroke care, respectively. We found that measurement of the adherence rates of the developed QIs using the existing DPC database was feasible for the 6 QIs (primary stroke care: early and discharge antithrombotic drugs, mean 54.6% and 58.7%; discharge anticoagulation for atrial fibrillation, 64.4%; discharge antihypertensive agents, 51.7%; comprehensive stroke care: fasudil hydrochloride or ozagrel sodium for vasospasm prevention, 86.9%; death complications of diagnostic neuroangiography, 0.4%). We found wide inter-hospital variation in QI adherence rates based on hospital characteristics. Conclusions We developed QIs for primary and comprehensive stroke care. The DPC database may allow efficient data collection at low cost and decreased burden to evaluate the developed QIs.

Visual Abstract, Treatment options for cerebral infarction beyond the time window of reperfusion therapy are limited, and novel approaches are needed. PDGF-B is considered neuroprotective; however, it is difficult to administer at effective concentrations to infarct areas. Nanoparticles (NPs) are small and stable; therefore, we modified PDGF-B to the surface of naturally occurring heat shock protein NPs (HSPNPs) to examine its therapeutic effect in cerebral infarction. PDGF-B modified HSPNPs (PDGF-B HSPNPs) were injected 1 d after transient middle cerebral artery occlusion (t-MCAO) in CB-17 model mice. We analyzed the infarct volume and motor functional recovery at 3 and 7 d. PDGF-B HSPNPs were specifically distributed in the infarct area, and compared with HSPNPs alone, they significantly reduced infarct volumes and improved neurologic function 3 and 7 d after administration. PDGF-B HSPNP administration was associated with strong phosphorylation of Akt in infarct areas and significantly increased neurotrophin (NT)-3 production as well as reduced cell apoptosis compared with HSPNPs alone. Moreover, astrogliosis in peri-infarct area was significantly upregulated with PDGF-B HSPNPs compared with HSPNPs alone. Treatment with PDGF-B HSPNPs might be a novel approach for treating cerebral infarction.

The epidemiology of patients with traumatic brain injury (TBI) has changed dramatically over recent decades as a result of rapid advances in aging societies. We assessed the influence of age on outcomes of patients with TBI and sought to identify prognostic factors for in-hospital mortality of TBI among elderly patients.Using a nationwide database, we analyzed data from 5651 patients with TBI. Univariate analysis was conducted to compare patient demographics, neurologic status on admission, radiologic findings, systemic complication rates, length of hospital stay, in-hospital mortality, and home discharge rates between elderly and nonelderly groups. Multivariable analysis was conducted to determine prognostic factors for in-hospital mortality among elderly patients.Overall in-hospital mortality was significantly higher in elderly patients (12.8% vs. 19.3%; P0.001). In-hospital mortality of elderly patients with mild TBI increased significantly at7 days after admission, whereas that of elderly patients with moderate or severe TBI was significantly higher immediately after admission. Age (odds ratio [OR], 1.62; P = 0.024), male sex (OR, 1.30; P = 0.004), Japan Coma Scale score on admission (OR, 5.95, P0.001), and incidence of acute subdural hematoma (OR, 1.89; P0.001) were associated with in-hospital mortality in elderly patients with TBI.Elderly patients with TBI showed significantly higher in-hospital mortality. Delayed increases in in-hospital mortality were observed among elderly patients with mild TBI. Level of consciousness on admission was the strongest predictor of in-hospital mortality among elderly patients.

Background: Improving the quality of stroke care is an urgent issue worldwide. To facilitate the measurement of quality of stroke care in Japan, we aimed to develop the Close The Gap-Stroke initiative in the J-ASPECT Study. Methods and Results: Quality indicators (QIs) were developed by a multidisciplinary board between 2015 and 2017. The process involved a systematic review of domestic and international studies related to primary and comprehensive stroke care. Adherence rates for the defined QIs were calculated for 8,826 patients with acute ischemic stroke from 227 hospitals between 2013 to 2015. Seventeen and 12 measures were identified as QIs for primary and comprehensive stroke care (PSC and CSC), respectively. We analyzed adherence rates of all 17 QIs for PSC and 8 QIs for CSC related with acute ischemic stroke. We found NIHSS documentation (91.0 %), CT/MRI performed within 25min and 24hr (80.9 % and 99.1 %), evaluation of extracranial vascular imaging (90.4 %), treated in stroke unit (57.4 %), tPA administration (89.5 %), tPA performed within 1hr (37.4 %), early and discharge antithrombotics medication (75.1 % and 49.0 %), discharge anticoagulation for atrial fibrillation patients (76.2 %), discharge statin medication (32.7 %), discharge antihypertensive agents (54.3 %), deep vein thrombosis prophylaxis (34.5 %), early rehabilitation (57.0 %), dysphagia screening (76.6 %), smoking cessation (59.8 %) and stroke education (71.4 %) for primary stroke care; and median time to multimodal CT or MR brain and vascular imaging (33 min), proper endovascular recanalization (81.7 %), tPA before endovascular recanalization (65.7 %), TICI grade 2b/3 after endovascular recanalization (73.0 %), median time of door to puncture (105 min), symptomatic intracranial hemorrhage after thrombolytic or endovascular therapy (7.45 %), 90 days mRS documentation after thrombolytic or endovascular therapy (60.8 %), occurrence of complication within 24 hours of diagnostic neuroangiography (7.27 %) for comprehensive stroke care. Conclusion: This is a promising first step to measure the QIs related to primary and comprehensive stroke care at a national level in Japan.

Objective: We performed a nationwide study to evaluate the effectiveness of stent-retriever in addition to intravenous thrombolysis in acute ischemic stroke patients in the ‘‘real-world’’ settings. Methods: This was a retrospective cohort study using the Diagnosis Procedure Combination nationwide inpatient database in Japan. Patients with acute ischemic stroke who were admitted to hospitals between April 1, 2013, and March 31, 2014 were identified. The rate of functional independence (modified Rankin scale score, 0 to 2) at discharge and mortality at 30 days were compared between patients who received intravenous thrombolysis alone (IVT group) and those who received stent-retriever after intravenous thrombolysis (IVET group) using 1:1 propensity score-matching. Results: In total, 71,519 acute ischemic patients were identified in a year. Among those, 3,367 patients were eligible (3,110 in IVT group and 257 in IVET group). Post-matching, 134 pairs of patients were analysed. The rate of functional independence at discharge was higher in IVET group than in IVT group (odds ratio 1.96, 95% CI 1.16-3.35; p=0.012). In addition, there was no significant differences in mortality at 30 days between the two groups (odds ratio 1.80, 95% CI 0.81-4.23; p=0.153). Conclusion: This nationwide study revealed that mechanical thrombectomy with stent-retriever in addition to intravenous thrombolysis improves functional outcomes in patients with acute ischemic stroke, and with no evidence of increased mortality. A randomized clinical trial seems warranted.

Background: Many studies have reported that high-volume center was associated with the favorable outcomes in subarachnoid hemorrhage (SAH) patients with treatment. However, in Japan, the effect of the case volume of the hospital in SAH patients remains elusive. The aim of this study is to investigate the associations between case volume and outcomes of clipping or coiling using data obtained from the Japanese Diagnosis Procedure Combination [DPC]-based Payment System. Methods: Of the 847 certified training institutions of the Japan Neurosurgical Society, 327 institutions agreed to participate in this DPC discharge database study. Data on patients hospitalized for SAH between April 1, 2012 and March 31, 2013 were obtained from the DPC database. Patients hospitalized because of SAH were identified using International Classification of Diseases-10 diagnosis codes (I60.0-9). The case volumes of clipping and coiling in each hospital were divided into quintiles (Q1-Q4). Odd ratios (ORs) of in-hospital mortality and modified Rankin Scale (mRS) at discharge were estimated after adjustment for age, sex, comorbidities, and SAH severity. The category of Q1 was assigned a reference for OR. Results: A total of 5214 patients with SAH (3624 clipping, 1590 coiling) were analyzed. Mortality was 9.8%, and proportion of discharge mRS3-6 was 44.0%. No significant associations were found between case volume and in-hospital mortality in both the clipping (Q2, Q3, and Q4; OR = 0.97, 0.69, and 0.77; P = 0.902, 0.148, and 0.263) and coiling group (Q2, Q3, and Q4; OR = 0.94, 1.62, and 0.84; P = 0.864, 0.140, and 0.586). No significant associations were found between case volume and discharge mRS3-6 in both the clipping (Q2, Q3, and Q4; OR = 1.28, 1.27, and 1.09; P = 0.194, 0.189, and 0.619) and coiling group (Q2, Q3, and Q4; OR = 0.89, 1.15, and 0.78; P = 0.691, 0.599, and 0.315). Conclusion: In Japan, case volume did not show the correlation with outcomes in SAH patients. This nationwide database study reflects the real-world practice.

Introduction: Certification system of the primary and comprehensive stroke center (PSC and CSC) is still under discussion in Japan. This study attempts to examine associations between the variation of stroke center capabilities and the improvement of outcomes for acute ischemic stroke on a national scale. Hypothesis: Improvements in hospital stroke center capabilities leads to better outcome of acute ischemic stroke patients. Methods: Using a validated score for evaluating CSC capabilities, which consists of 5 categories (personnel, diagnostic techniques, specific expertise, infrastructure, and education) on a 25 point scale, we assessed CSC capabilities for 137 certified training hospitals in 2011 and 2015 (Kada et al. BMC Neurol 2017). A consecutive health insurance claims data known as the Japanese Diagnosis Procedure Combination/Per Diem Payment Systems of 2011 and 2015 was obtained from the hospitals. The proportion of favorable outcome—score 0 to 1 on the modified Rankin Scale (mRS)—at discharge was quantified as the primary outcome. The change in CSC score with more than two points over time was quantified as an independent variable. We regressed the change of CSC score on morbidity with adjustment of average age and sex in the hospitals. Results: In total, 18,658 in 2011 and 29,999 in 2015 ischemic stroke patients were admitted to 137 hospitals. Median annual number of ischemic stroke patients per hospital increased from 115 to 183 over time. Mean age (74.5 year vs 74.2 years) and proportions of men (56.8% vs 58.2%) were almost the same. The mean CSC scores increased from 15.9±4.0/25 to 17.2±4.2/25 point. The mean hospital mortality decreased from 6.1% to 4.3%. The mean proportion of patients with the favorable outcome at discharge increased from 39.2% to 45.5%. We selected random-effect model based on Housman test. In regression analyses, the increase of CSC score over time was significantly associated with the increasing proportion of the favorable outcome at discharge (coefficient, 2.76; 95% CI, 0.04-5.47; p-value, 0.047). Conclusions: Improvements in CSC capabilities overtime was significantly related to the improvement of functional outcome at discharge in ischemic stroke patients.

Introduction: In recent years, the treatment of the acute phase of cerebral infarction such as tPA and endovascular thrombectomy has been rapidly changing, and development of a medical system for acute cerebral infarction is desired. Objective: To examine the effect of tPA and endovascular thrombectomy on mortality in patients with acute ischemic stroke in the nationwide 5 years hospital cohort in Japan. Methods: We conducted annual nationwide survey from 2011 to 2015 using data from the Japanese Diagnosis Procedure Combination database on patients hospitalized with ischemic and hemorrhagic stroke in a nationwide hospital cohort in Japan (J-ASPECT Study). The effect of tPA or endovascular thrombectomy on stroke mortality was analyzed by mixed effect model with years (from 2011 to 2015), age, gender, Japan Coma Scale (JCS), and Comprehensive stroke care (CSC) score as a fixed effect, and hospital as a random effect. CSC score was developed by our study group based on the institutional survey conducted in 2011. Results: The total numbers of patients were 292,230 in ischemic stroke. In 5 years, the proportion of tPA or endovascular thrombectomy has increased from 7.2% to 8.4%, while the mortality has decreased from 7.6% to 5.5%. The mortality varied by JCS, which was 37.5% for JCS 3 digit, 15.4% for JCS 2 digit, 4.8% for JCS 1 digit and 1.4% for JCS 0 in 2015. In the analysis of subjects with severe JCS 3 digit, years (OR = 0.97, 95% CI = 0.94 - 1.00), CSC score increase (0.98, 95% CI = 0.97 - 0.99), and tPA or endovascular thrombectomy (OR = 0.75, 95% CI = 0.67 - 0.84) were found to reduce the risk of death. Conclusion: According to the analysis of patients with acute ischemic stroke for 5 years, tPA or endovascular thrombectomy was related to reduced mortality in subjects with high severity.

Objective: We previously demonstrated comprehensive stroke care (CSC) capabilities of the hospitals affect in-hospital mortality of patients with acute stroke. With the advent of unprecedented aging society, proper implementation of stroke centers requires understanding of geographical disparity of patient characteristics as well as stroke care capabilities. The aim of this study was to elucidate such geographical disparity regarding acute stroke care in Japan using a nationwide database. Materials and methods: We analyzed the data obtained from the Japanese Diagnosis Procedure Combination-based Payment System in 445 institutions between 2010 and 2012. Patients hospitalized emergently for ischemic stroke(IS), non-traumatic intracerebral hemorrhage(ICH) and non-traumatic subarachnoid hemorrhage(SAH) were identified using International Classification of Diseases-10 diagnosis codes. We classified the location of the hospitals into 4 areas, “Metropolitan Employment Area-Central (MEA-C)”, “ Metropolitan Employment Area-Outlying (MEA-O)”, “Micropolitan Employment Area-Central (McEA-C)”, and “ Micropolitan Employment Area-Outlying (McEA-O)”. We investigated patient characteristics, medical backgrounds, interventions and outcomes for each area. Results: Data obtained from a total of 214,910 patients with acute strokes (136,753 IS, 60,379 ICH and 17,778 SAH) were analyzed. As for patient characteristics, elderly patients and those with hypertension were more common in McEA-C and McEA-O, and stroke severity was more severe in McEA-C in all stroke types. As for hospital characteristics, proportion of admission by ambulance and CSC capabilities of the hospitals were smaller in all stroke types. Moreover, emergent interventions such as intravenous rt-PA infusion were performed at a lesser extent and in-hospital mortality was higher in McEA-C and McEA-O, and severe disability with mRS 3-6 was more often noted in McEA-C in all stroke types. Conclusion: We demonstrated geographical disparity of acute stroke care in Japan from a nationwide database. For proper implementation of stroke centers, centralization of acute stroke care capabilities should be considered in the rural areas to improve outcomes of acute stroke.

Objective: This study aimed to investigate recent nationwide trends in the epidemiology of acute ischemic stroke (AIS) in Japan. Methods: We analyzed 328,147 acute ischemic stroke patients in 350 certified training hospitals in Japan using data obtained from the Japanese Diagnosis Procedure Combination Database. Data between the period April 1, 2010 and May 31, 2014 were used. We divided patients into three treatment groups: medical treatment only (group M), intravenous t-PA infusion only (group IVT), and endovascular treatment (group ET). Outcome was assessed by in-hospital mortality and modified Rankin Scale (mRS) score at discharge, and poor outcome was defined as a mRS score of 3-6. Results: The patient proportion in groups M, IVT, and ET changed from 94.3%, 3.2%, and 1.6% in 2010 to 90.9%, 4.3%, and 3.7% in 2014, respectively (P Conclusion: In Japan, during the 5-year period before the guidelines concerning proper use of ET for AIS were revised in 2015, a significant improvement in in-hospital mortality and functional outcomes of AIS patients undergoing medical treatment and intravenous rt-PA infusion was observed. This was probably due to a gradual increase in the proportion of patients undergoing IVT; the outcomes of ET, however, remained the same.

Background: The effectiveness of comprehensive stroke center (CSC) capabilities on outcome of carotid endarterectomy (CEA) and carotid artery stenting (CAS) remains uncertain. We performed a nationwide study to examine whether CSC capabilities influenced in-hospital outcome of CEA and CAS. Methods: We analyzed 12,943 carotid artery stenosis patients treated with CEA or CAS in 350 certified training hospitals in Japan. Data between April 1, 2013 and May 31, 2015 was obtained from Japanese Diagnosis Procedure Combination Database. Among the institutions that responded, outcome was assessed by in-hospital mortality, ischemic stroke and myocardial infarction. CSC capabilities were evaluated from the 749 certified training institutions in Japan, which responded to a questionnaire survey regarding CSC capabilities that queried the availability of personnel, diagnostic techniques, specific expertise, infrastructure, and educational components recommended for CSCs. Total CSC scores of the participating hospitals were classified into quartiles (Q1: 0-15, Q2: 16-17, Q3: 18-19, Q4: 20-24). Results: The proportion of CEA and CAS were 5068 and 7875 (2013: 1685 and 2590, 2014: 1668 and 2564, 2015: 1715 and 2721). Between CEA and CAS, mortality rates were 0.24% and 0.75%, ischemic stroke were 8.41% and 7.56% and myocardial infarction were 0.76% and 0.17%. These outcomes had no differences among the years. There was tendency that mortality rates were lower with high total CSC scores in patients with CEA (Q1: 0.42%, Q2: 0.26%, Q3: 0.12%, Q4: 0%, P=0.16), but there were no differences with CAS (Q1: 1.0%, Q2: 0.74%, Q3: 0.63%, Q4: 0.83%, P=0.73). Ischemic stroke were significantly lower with high CSC scores in CEA (Q1: 9.76%, Q2: 10.77%, Q3: 9.14%, Q4: 6.59%, P Conclusion: It is reported using the data of Nationwide Inpatient Sample that operator volume was an important predictor of postprocedural outcomes in CAS. We demonstrated that CSC capabilities were associated with reduced in-hospital ischemic stroke in patients with CEA and CAS.

Background and purpose: The incidence of non-traumatic intracranial hemorrhage (ICH) during treatment with direct oral anticoagulants (DOACs) is lower than that during warfarin treatment. The characteristics of intracranial hemorrhage during DOAC therapy, however, remain unclear. Therefore, we performed a nationwide survey in Japan to examine the clinical characteristics and outcomes of DOAC-associated ICH using data obtained from the Japanese Diagnosis Procedure Combination (DPC)-based Payment System. Methods: We analyzed the data of 1,567 patients with ICH (DOAC-associated ICH, 88; warfarin-associated ICH, 1,479) who were urgently hospitalized at 575 institutions across Japan from April 2010 to March 2013 for whom prescription data before admission were available. Results: The annual number of patients with all anticoagulant (DOAC or warfarin)- associated ICH in each year from 2010 to 2013 was 226, 252, 426, and 663, representing 15.7%, 15.4%, 16.1%, and 16.1% of all ICH cases in the same period, respectively. There was an increase in the proportion of patients who presented with DOAC-associated ICH in all anticoagulant-associated ICH in each year from 2010 to 2013 (0%→0.4%→3.8%→10.7%). The proportion of patients with impaired consciousness (three-digit score on Japan Coma Scale) at admission (DOAC, 19.3%; Warfarin, 25.4%; P=0.20), in-hospital mortality within 7 days (DOAC, 11.4%; Warfarin, 19.5%; P=0.06), and mRS score of 5-6 at discharge (DOAC, 27.3%; Warfarin, 37.4%; P=0.06) were lower in the patients with DOAC-associated ICH. The rates of surgery for hematoma removal were significantly lower in the patients with DOAC-associated ICH (NOAC, 2.3%; Warfarin, 9.7%; P=0.019). Conclusions: This is the largest nationwide study of DOAC-associated ICH in a real-world situation in Japan, revealing that the patients with DOAC-associated ICH had better clinical outcomes compared with warfarin-associated ICH, probably due to milder hemorrhage at admission.

Background and purpose: The outcomes of subarachnoid hemorrhage (SAH) in aged patients are more severe than those in non-aged patients. There are few reports about the relationship between the age and the effect of perioperative care for SAH patients. We performed a nationwide survey in Japan to determine the relationship between perioperative care and SAH outcomes in aged and non-aged patients. Methods: We analyzed 17,343 subarachnoid hemorrhage (SAH) patients treated with clipping or coiling in 579 hospitals who participated in the J-ASPECT study. Data between 2010 and 2013 were obtained from the Japanese Diagnosis Procedure Combination Database. We stratified patients into two groups according to their age (aged group >75 y.o., n=3885; non-aged group < 75 y.o., n=13,458) and analyzed the association between perioperative care and poor outcome (modified Rankin Scale score 3-6 at the time of discharge). With respect to perioperative care, we evaluated time from onset to surgery (days), treatment (clipping or coiling), and drugs delivered after surgery (fasudil hydrochloride, ozagrel sodium, cilostazol, statin, EPA, edaravone). Results: In the non-aged group, coiling (OR=0.84; P Conclusion: Coiling and treatment with fasudil hydrochloride, statins, and EPA improved outcomes of non-aged patients. Although perioperative care did not improve the outcome of aged SAH patients, in cases of relatively mild SAH, perioperative care had the potential to improve the outcome.

Prediction of the disease status is one of the most important objectives of genetic studies. To select the genes with strong evidence of the association with type 2 diabetes mellitus, we validated the associations of the seven candidate loci extracted in our earlier study by genotyping the samples in two independent sample panels. However, except for KCNQ1, the association of none of the remaining seven loci was replicated. We then selected 11 genes, KCNQ1, TCF7L2, CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, HHEX, GCKR, HNF1B, KCNJ11 and PPARG, whose associations with diabetes have already been reported and replicated either in the literature or in this study in the Japanese population. As no evidence of the gene-gene interaction for any pair of the 11 loci was shown, we constructed a prediction model for the disease using the logistic regression analysis by incorporating the number of the risk alleles for the 11 genes, as well as age, sex and body mass index as independent variables. Cumulative risk assessment showed that the addition of one risk allele resulted in an average increase in the odds for the disease of 1.29 (95% CI=1.25-1.33, P=5.4 x 10(-53)). The area under the receiver operating characteristic curve, an estimate of the power of the prediction model, was 0.72, thereby indicating that our prediction model for type 2 diabetes may not be so useful but has some value. Incorporation of data from additional risk loci is most likely to increase the predictive power.

To explain the finding that motion assimilation was dominant between nearby motion signals while motion contrast between distant ones, a center-surround antagonistic mechanism was proposed [Nawrot & Sekuler (1990). Vision Research, 30, 1439–1451]. However, motion assimilation occurred not only between nearby signals but also between distant ones, suggesting the existence of a center-surround non-antagonistic mechanism [Ido, Ohtani & Ejima (1997). Vision Research, 37, 1565–1574]. The present study was designed to provide direct evidence for the non-antagonistic mechanism, and to examine further the motion interactions which operate in different spatial scales. The nature of motion interaction between the test and the inducer was examined by varying the size, the number of frames, the frame duration and the inter-frame displacement of random-dot kinematograms. The results were consistent with the notion that there are three types of interactions in human motion processing; one is a summation process effective within nearby regions, and the other two are facilitative and inhibitory induction processes operating over larger spatial scales. Analysis of the results in terms of the Fourier components suggests that the facilitative and the inhibitory induction processes may be sensitive, respectively to the lower and the higher temporal frequency components of the stimulus.

Objective To report a newly developed intraluminal triple-balloon shunt designed to preserve the blood flow of both the internal carotid artery (ICA) and the external carotid artery (ECA) during carotid endarterectomy in patients with a previous ipsilateral extracranial-intracranial bypass, in whom hemodynamic cerebral ischemia might be caused by cross-clamping at the ICA as well as the ECA. Methods The novel device consists of 3 silicone tubes equipped with balloons at each end. The design facilitates insertion proximally to the common carotid artery and distally to both the ICA and the ECA. Results The new shunt tube was used in 3 patients, each of whom had previously undergone ipsilateral superficial temporal artery–middle cerebral artery bypass for proximal middle cerebral artery occlusion. The blood flow of the middle cerebral artery and anterior cerebral artery was supplied independently from the ECA via the bypass and from the ICA, respectively. There were no shunt-related complications. Conclusions This novel shunt device can be used safely and effectively in cases requiring preservation of the blood supply to both the ICA and the ECA during carotid endarterectomy.

Here we report a case of spinal dural arteriovenous fistula that was diagnosed on MRA and CTA, and then treated by endovascular embolization. A 56-year-old male presented with slowly progressive intermittent claudication and numbness of the lower extremities. T2-weighted MR imaging showed the swelling of the spinal cord with an intramedullary high signal intensity area and dilated vessels with signal flow void at the dorsal aspect of spinal cord. Dynamic MRA demonstrated the feeding artery, shunt point and the overview of dilated veins as seen with a CTA. Endovascular embolization using liquid material was performed under local anesthesia. The injection of glue included the distal feeding artery, the shunt itself and the initial part of the draining vein. A complete cure was achieved. CTA after embolization demonstrated the glue cast and the disappearance of the AV shunt and dilated veins that were visible before embolization. It was suggested that dynamic MRA and CTA are useful for the final diagnosis and postoperative evaluation of spinal dural arteriovenous fistulas.

Background Variety of information relating between genome and the pathological findings in disease will yield a wealth of clues to discover new function, the role of genes and pathways, and future medicine. In addition to molecular information such as gene expression and genome copy number, detailed clinical information is essential for such systematic omics analysis. Results In order to provide a basic platform to realize a future medicine based on the integration of molecular and clinico-pathological information of disease, we have developed an integrated clinical omics database (iCOD) in which comprehensive disease information of the patients is collected, including not only molecular omics data such as CGH (Comparative Genomic Hybridization) and gene expression profiles but also comprehensive clinical information such as clinical manifestations, medical images (CT, X-ray, ultrasounds, etc), laboratory tests, drug histories, pathological findings and even life-style/environmental information. The iCOD is developed to combine the molecular and clinico-pathological information of the patients to provide the holistic understanding of the disease. Furthermore, we developed several kinds of integrated view maps of disease in the iCOD, which summarize the comprehensive patient data to provide the information for the interrelation between the molecular omics data and clinico-pathological findings as well as estimation for the disease pathways, such as three layer-linked disease map, disease pathway map, and pathome-genome map. Conclusions With these utilities, our iCOD aims to contribute to provide the omics basis of the disease as well as to promote the pathway-directed disease view. The iCOD database is available online, containing 140 patient cases of hepatocellular carcinoma, with raw data of each case as supplemental data set to download. The iCOD and supplemental data can be accessed at http://omics.tmd.ac.jp/icod_pub_eng

Objective With the aim of making good use of internationally accumulated genomic sequence variation data, which is increasing rapidly due to the explosive amount of genomic research at present, the development of an interoperable data exchange format and its international standardization are necessary. Genomic Sequence Variation Markup Language (GSVML) will focus on genomic sequence variation data and human health applications, such as gene based medicine or pharmacogenomics. Design and method We developed GSVML through eight steps, based on case analysis and domain investigations. By focusing on the design scope to human health applications and genomic sequence variation, we attempted to eliminate ambiguity and to ensure practicability. We intended to satisfy the requirements derived from the use case analysis of human-based clinical genomic applications. Based on database investigations, we attempted to minimize the redundancy of the data format, while maximizing the data covering range. We also attempted to ensure communication and interface ability with other Markup Languages, for exchange of omics data among various omics researchers or facilities. The interface ability with developing clinical standards, such as the Health Level Seven Genotype Information model, was analyzed. Results We developed the human health-oriented GSVML comprising variation data, direct annotation, and indirect annotation categories; the variation data category is required, while the direct and indirect annotation categories are optional. The annotation categories contain omics and clinical information, and have internal relationships. For designing, we examined 6 cases for three criteria as human health application and 15 data elements for three criteria as data formats for genomic sequence variation data exchange. The data format of five international SNP databases and six Markup Languages and the interface ability to the Health Level Seven Genotype Model in terms of 317 items were investigated. Conclusion GSVML was developed as a potential data exchanging format for genomic sequence variation data exchange focusing on human health applications. The international standardization of GSVML is necessary, and is currently underway. GSVML can be applied to enhance the utilization of genomic sequence variation data worldwide by providing a communicable platform between clinical and research applications.

In order to realize gene-based medicine, a number of key challenges must be overcome. Construction of infrastructure capable of integrating genetic and clinical information is one of those challenges. The Genomic Sequence Variation Markup Language (GSVML) and the Health Level Seven Version 3 (HL7v3) are important electronic data exchange standards for clinical genome infrastructure, and compatibility between these two standards will promote the above integration. In this study, we analyzed the interface between GSVML and HL7v3, primarily for the Clinical Genomics Domain, from a view of the GSVML, and were able to create a blueprint for a functional interface between GSVML and HL7v3. We expect that these analytical results will help accelerate the realization of gene-based medicine.

Two sets of experiments were carried out to examine dependencies of two types of induced motion (motion assimilation and motion contrast) on spatial properties of stimuli in terms of spatial-frequency tuning of local motion detectors. In the first set, the magnitudes of motion assimilation and motion contrast for a sinusoidal grating were measured as a function of the spatial frequency of the inducing gratings, with the spatial frequency of the test grating as a parameter. In the second set, the magnitudes were measured as a function of the height of the inducing gratings with the spatial frequencies of the test and the inducing gratings as parameters. For motion assimilation, the magnitude was characterized by a low-pass function of the spatial frequency of the inducing gratings, and the critical height of the inducing gratings, which demarcates the extent of the spatial pooling, varied systematically depending on the spatial frequency of the inducing gratings. For motion contrast, on the other hand, the magnitude was characterized by a band-pass function, and the critical height depended on the frequency of the test grating. These results suggest that motion assimilation is mediated by the spatial-frequency nonselective interaction between the local detectors, in which the motion signals of the detectors tuned to different spatial frequencies are integrated with each other. Motion contrast is mediated by the spatial-frequency selective interaction, in which the motion signals of the local detectors tuned to the same or similar spatial frequencies are compared and differentiated. © 1997 Elsevier Science Ltd.

When a sinusoidal (test) grating is displaced horizontally by a phase angle of 180 deg in a two-frame apparent motion display, the perceived direction of motion is ambiguous; the test grating appears to move either to the left or to the right (or to both directions). On the other hand, when the test grating is displaced by 180 deg synchronously with the inducing gratings which, presented above and below the test grating, jump unambiguously in one direction (e.g. displaced by 90 deg), the test grating always appears to move in the same direction as the inducing gratings (motion assimilation). In the present study, the effects of luminance contrast and phase difference on motion assimilation were examined. The proportion of perceived direction of motion (left or right) was measured as a function of phase difference between the test grating in the first and the second frame. The magnitude of motion assimilation was evaluated as the change in the phase difference for which the proportions of observers' response were equal (50%) for both directions. The magnitude of motion assimilation increased with increase in the contrast of the inducing gratings or with decrease in the contrast of the test grating. Also, the magnitude increased as the phase difference of the inducing gratings departed from 180 deg. Based on these results, a quantitative formulation between the magnitude of motion assimilation, and the contrast and the phase difference of the stimulus gratings was derived. Further, a model was proposed which explains the stimulus dependences of motion assimilation in terms of response-integration among local motion detectors.

Using colored inducing patterns presented as increments upon a white uniform background, the increment thresholds needed for illusory contour perception were measured as a function of the wavelength of inducing pattern. The spectral sensitivity functions were obtained with varying adaptation level and stimulus configuration, high and low background illumination, and line-based and figure-based inducing patterns. The results showed a distinctive feature between the line-based and the figure-based illusory contours. The sensitivity functions for the line-based illusory contours showed the characteristics of non-opponent mechanisms and they were shape invariant with background intensity and spatial variables. On the other hand, the sensitivity functions for the figure-based illusory contours showed non-opponent nature for low background illumination but opponent nature for high background illumination. It is suggested that the generation of illusory contours involves concurrent processing of different cues of luminance and color, and that photopic adaptation level and stimulus configuration control the degree of the contributions of chromatic and achromatic mechanisms to contour formation.