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High levels of high-density lipoprotein cholesterol (HDL-C) are not necessarily effective in preventing atherosclerotic cardiovascular disease, and cholesterol efflux capacity (CEC) has attracted attention regarding HDL functionality. We aimed to elucidate whether drinking habits are associated with CEC levels, while also paying careful attention to confounding factors including serum HDL-C levels, other life style factors, and rs671 (A cross-sectional study was performed in 505 Japanese male subjects who were recruited from a health screening program. Associations of HDL-C and CEC levels with drinking habits and ALDH2 genotypes were examined.The genotype frequencies of ALDH2Our results suggest that heavy drinking habits may tend to decrease CEC levels, and in the ALDH2

Aims. This study is aimed at clarifying the relationship between visit-to-visit variability of glycated hemoglobin (HbA1c) and the risk of diabetic kidney disease (DKD) and to identifying the most useful index of visit-to-visit variability of HbA1c. Methods. This clinic-based retrospective longitudinal study included 699 Japanese type 2 diabetes mellitus patients. Visit-to-visit variability of HbA1c was calculated as the internal standard deviation of HbA1c (HbA1c-SD), the coefficient of variation of HbA1c (HbA1c-CV), the HbA1c change score (HbA1c-HVS), and the area under the HbA1c curve (HbA1c-AUC) with 3-year serial HbA1c measurement data, and the associations between these indices and the development/progression of DKD were examined. Results. Cox proportional hazards models showed that the HbA1c-SD and HbA1c-AUC were associated with the incidence of microalbuminuria, independently of the HbA1c level. These results were verified and replicated in propensity score (PS) matching and bootstrap analyses. Moreover, the HbA1c-SD and HbA1c-AUC were also associated with oxidized human serum albumin (HSA), an oxidative stress marker. Conclusions. Visit-to-visit variability of HbA1c was an independent risk factor of microalbuminuria in association with oxidative stress among type 2 diabetes mellitus patients. HbA1c-AUC, a novel index of HbA1c variability, may be a potent prognostic indicator in predicting the risk of microalbuminuria.

Fusobacterium nucleatum has been detected in 8%‐13% of human colorectal cancer, and shown to inhibit immune responses against primary colorectal tumors in animal models. Thus, we hypothesized that the presence of F. nucleatum might be associated with reduced T cell density in colorectal cancer liver metastases (CRLM). We quantified F. nucleatum DNA in 181 CRLM specimens using quantitative PCR assay. The densities of CD8+ T cells, CD33+ cells (marker for myeloid‐derived suppressor cells [MDSCs]), and CD163+ cells (marker for tumor‐associated macrophages [TAMs]) in CRLM tissue were determined by immunohistochemical staining. Fusobacterium nucleatum was detected in eight (4.4%) of 181 CRLM specimens. Compared with F. nucleatum‐negative CRLM, F. nucleatum‐positive CRLM showed significantly lower density of CD8+ T cells (P = .033) and higher density of MDSCs (P = .001). The association of F. nucleatum with the density of TAMs was not statistically significant (P = .70). The presence of F. nucleatum is associated with a lower density of CD8+ T cells and a higher density of MDSCs in CRLM tissue. Upon validation, our findings could provide insights to develop strategies that involve targeting microbiota and immune cells for the prevention and treatment of CRLM., Fusobacterium nucleatum was detected in eight (4.4%) of 181 colorectal cancer liver metastasis tissue. We found that the presence of F. nucleatum was associated with lower CD8+ T cell density and greater densities of both myeloid‐derived suppressor cells and tumor‐associated macrophages.

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%.

External genitalia development in mice involves multiple developmental processes under the regulation of various signaling pathways. Wnt5a, one of the major Wnt ligands, is a crucial developmental regulator of outgrowing organs such as the limb, the mandible, and the external genitalia. Defects in Wnt5a signaling have been linked to Robinow syndrome, a genetic disorder in which male patients manifest a micropenis and defective urethral tube formation. Whereas Wnt5a is required for cell proliferation during embryonic external genitalia outgrowth, its role for urethral tube formation has yet to be understood. Here, we show that Wnt5a contributes to urethral tube formation as well as external genitalia outgrowth. Wnt5a is expressed in the embryonic external genitalia mesenchyme, and mesenchymal-specific conditional Wnt5a knockout mice resulted in hypospadias-like urethral defects. Early deletion of Wnt5a at E10.5 showed severe defects in both external genitalia outgrowth and urethral tube formation, along with reduced cell proliferation. The severe urethral tube defect persisted during later timing deletion of Wnt5a (E13.5). Further analyses revealed that loss of Wnt5a disrupted cell polarity and led to a reduction of the phosphorylated myosin light chain and the focal adhesion protein, vinculin. Altogether, these results suggest that Wnt5a coordinates cell proliferation and directed cell migration in a stage-dependent manner during male external genitalia development. Furthermore, Wnt5a may regulate cell polarity, focal adhesion formation, and cell contractility, leading to directed cell migration during male-type urethral formation in a manner that has not been reported in other organ fusion events.

Background: Although the prognostic relevance of KRAS status in metastatic colorectal cancer (CRC) depends on tumor laterality, this relationship is largely unknown in non-metastatic CRC. Methods: Patients who underwent resection for non-metastatic CRC between 2000 and 2018 were identified from institutional databases at six academic tertiary centers in Europe and Japan. The prognostic relevance of KRAS status in patients with right-sided (RS), left-sided (LS), and rectal cancers was assessed. Results: Of the 1093 eligible patients, 378 had right-sided tumors and 715 had left-sided tumors. Among patients with RS tumors, the 5-year overall (OS) and recurrence-free survival (RFS) for patients with KRASmut versus wild-type tumors was not shown to differ significantly (82.2% vs. 83.2% and 72.1% vs. 76.7%, respectively, all p >.05). Among those with LS tumors, KRAS mutation was associated with shorter 5-year OS and RFS on both the univariable (OS: 79.4% vs. 86.1%, p =.004; RFS: 68.8% vs. 77.3%, p =.005) and multivariable analysis (OS: HR: 1.52, p =.019; RFS: HR: 1.32, p =.05). Conclusions: KRAS mutation status was independently prognostic among patients with LS tumors, but this association failed to reach statistical significance in RS and rectal tumors. These findings confirm reports in metastatic CRC and underline the possible biologic importance of tumor location.

Purpose In 2-dimensional lateral cephalometric radiographs, patients with severe obstructive sleep apnea (OSA) exhibit a more crowded oropharynx in comparison with non-OSA. We tested the hypothesis that machine learning, an application of artificial intelligence (AI), could be used to detect patients with severe OSA based on 2-dimensional images. Methods A deep convolutional neural network was developed (n = 1258; 90%) and tested (n = 131; 10%) using data from 1389 (100%) lateral cephalometric radiographs obtained from individuals diagnosed with severe OSA (n = 867; apnea hypopnea index > 30 events/h sleep) or non-OSA (n = 522; apnea hypopnea index Results The sensitivity/specificity was 0.87/0.82 for full image, 0.88/0.75 for main region, 0.71/0.63 for head only, and 0.54/0.80 for the manual analysis. The area under the receiver-operating characteristic curve was the highest for main region 0.92, for full image 0.89, for head only 0.70, and for manual cephalometric analysis 0.75. Conclusions A deep convolutional neural network identified individuals with severe OSA with high accuracy. Future research on this concept using AI and images can be further encouraged when discussing triage of OSA.

Introduction: Intracerebral hemorrhage (ICH) is a devastating hemorrhagic event and is associated with high mortality or severe neurological sequelae. Age-associated differences in hematoma location for nonlobar ICH are not well known. The aims of the present study were to elucidate the relationship between age and hematoma location and to assess the differences in small-vessel disease (SVD) burden as a potential surrogate marker for longstanding hypertension among various hematoma locations. Methods: From September 2014 through July 2019, consecutive patients with acute, spontaneous ICH were retrospectively enrolled from a prospective registry. Magnetic resonance imaging was performed during admission, and the total SVD burden score (including microbleeds, lacunes, enlarged perivascular spaces, and white matter hyperintensities) was calculated. The relationships of hematoma location with aging and SVD burden were assessed by using multivariate logistic regression analyses. Results: A total of 444 patients (156 women [35%]; median age 69 [interquartile range 59–79] years; National Institutes of Health Stroke Scale score 9 [17][3–17]) were enrolled in the present study. Multivariate logistic regression analyses showed that advanced age was independently associated with thalamic (odds ratio [OR]: 1.48, 95% confidence interval [CI]: 1.19–1.84, p < 0.001 for 10-year increment) and lobar hemorrhage (OR: 1.58, 95% CI: 1.19–2.09, p = 0.002) and was independently and negatively related to putaminal hemorrhage (OR: 0.55, 95% CI: 0.44–0.68, p < 0.001). The total SVD burden score was independently and positively associated with thalamic hemorrhage (OR: 1.27, 95% CI: 1.01–1.59, p = 0.045) and negatively with lobar hemorrhage (OR: 0.74, 95% CI: 0.55–0.99, p = 0.042), even after adjusting by age, but not with putaminal hemorrhage (OR: 0.91, 95% CI: 0.73–1.14, p = 0.395). Conclusion: Putaminal, thalamic, and lobar hemorrhages are prone to occur in specific ages and SVD states: putaminal in young patients, thalamic in old and high SVD burden patients, and lobar hemorrhages in old and low SVD burden patients. Susceptibility to bleeding with aging or severe SVD accumulation seems to differ considerably among brain locations.

Aim: The predictors of restenosis after endovascular therapy (EVT) with paclitaxel drug-coated balloons (DCBs) have not been clearly established. The present study aimed to investigate the association of post-procedural dissection, as evaluated using intravascular ultrasound (IVUS), with the risk of restenosis following femoropopliteal EVT with paclitaxel DCBs. Methods: In the present single-center retrospective study, 60 de novo femoropopliteal lesions (44 patients) that underwent EVT with DCBs, without bail-out stenting, were enrolled. The primary outcome was 1-year primary patency. Risk factors for restenosis were evaluated using a Cox proportional hazards regression model and random survival forest analysis. Results: The 1-year primary patency rate was 57.2% [95% confidence interval, 45%–72%]. IVUS-evaluated post-procedural dissection was significantly associated with the risk of restenosis ( P =0.002), with the best cutoff point of 64o [range, 39o–83o]. The random survival forest analysis showed that the variable importance measure of IVUS-evaluated dissection was significantly lower than that of the reference vessel diameter ( P ＜0.001), not different from that of the lesion length ( P =0.41), and significantly higher than that of any other clinical feature (all P ＜0.05). Conclusion: IVUS-evaluated post-procedural dissection was associated with 1-year restenosis following femoropopliteal EVT with DCB.

BACKGROUND AND PURPOSE Urinary liver-type fatty-acid binding protein (L-FABP), which is a biomarker of kidney tubule injury, has been studied extensively and established as a risk marker of acute kidney injury (AKI). The aim of this study was to investigate whether kidney tubule injury is associated with the development of AKI and mortality in patients with acute ischaemic stroke. METHODS Acute ischaemic stroke patients hospitalized in the stroke care unit (SCU) within 24 h after symptom onset were prospectively investigated. AKI was defined on the basis of Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Baseline urinary L-FABP was measured on admission. We evaluated the associations among urinary L-FABP, incidence of AKI, and 90-day mortality adjusted for renal function, albuminuria and other potentially predictive variables, using multivariable analysis. RESULTS In total, 527 acute ischaemic stroke patients (342 men, median age 74 years) were enrolled in the study. Twenty-seven patients (5.1%) experienced AKI within 7 days of admission. In the univariate analysis, high urinary L-FABP level had positive associations with AKI [53.8 μg/g creatinine (Cr) vs. 3.9 μg/g Cr; P

Some hyperacute stroke patients have unfavorable outcomes after endovascular thrombectomy (EVT) despite successful recanalization. We hypothesized that a cardiac parameter, moderate-to-severe mitral regurgitation (MR), might decrease the rate of favorable clinical outcome after EVT in patients with atrial fibrillation (AF).From our prospective EVT registry, AF patients who underwent transthoracic echocardiography (TTE) were retrospectively analyzed. Based on the presence of moderate-to-severe MR, patients were assigned to either significant MR or nonsignificant MR group. The severity of MR was determined by the ratio of the color Doppler jet area to the left atrial area in mid-systole. Moderate-to-severe MR was estimated to be at a ratio of20%. Favorable outcome was defined as having a modified Rankin Scale score of 0-1 at 3 months.127 patients with AF who underwent TTE were included in the study. TTE results found that 25 (20%) patients had significant MR. Patients with significant MR were older (p = 0.051) and had enlarged left (p = 0.015) and right (p = 0.002) atria. Tricuspid and aortic regurgitation (p = 0.007 and 0.043, respectively) were more severe in significant MR group. At 3 months, favorable outcomes were 11% in the significant MR group and 26% in the non-significant MR group (p = 0.031). Multivariate regression analysis reported that moderate-to-severe MR was a negative predictor of favorable outcome (odds ratio = 0.14; 95% confidence interval = 0.02, 0.84; p = 0.031).Significant MR might prevent the clinical recovery of AF patients.

BackgroundThe feasibility of performing MRI first for patients with suspected hyperacute stroke in real-world practice has not been fully examined. Moreover, most past studies of reducing door-to-reperfusion time (DRT) in endovascular treatment (EVT) were conducted using CT. The aim of this study was to evaluate the feasibility of an MRI-first policy and to examine the effects of a quality improvement (QI) process for reducing DRT using MRI.MethodsFrom January 2013 to December 2018, consecutive patients with acute stroke who came to hospital directly and were treated with emergent EVT were prospectively enrolled into the present study. In principle, MRI was performed first for patients with suspected acute stroke. A step-by-step QI process for decreasing DRT was adopted during this period. Time metrics for EVT were compared between specific time periods.ResultsA total of 180 patients (71 women; median age 76 years (range 69–64); National Institutes of Health Stroke Scale score 17 (range 10–23)) were included in the present study. More patients in the late phase were managed with the MRI-first policy (pConclusionAn MRI-first policy was feasible, and DRT decreased considerably with a step-by-step QI process. This process may be applicable to other hospitals.

The effects of FM system fitted into the normal hearing ear (NHE) or a cartilage conduction hearing aid (CCHA) fitted into the affected ear (AE) on the speech recognition ability in noise were examined in children with unilateral congenital aural atresia (UCAA). In children with bilateral normal hearing (BNH), speech recognition score (SRS) was significantly decreased in the noisy environment of -5 dB signal-to-noise ratio (SNR), compared with those in quiet. In children with UCAA, SRS was significantly decreased in noisy environments of 0 and -5 dB SNR, compared with those in quiet. In noisy environments of 0 and -5 dB SNR, SRS in children with UCAA was significantly decreased, compared those in children with BNH. In the noisy environment of -5 dB SNR, SRS in UCAA children aided by FM system fitted into NHE was significantly better than those in unaided children in the same group. In the noisy environment of 0 dB SNR, SRS in UCAA children aided by CCHA into AE tended to be higher than those in unaided children in the same group. FM system and CCHA can be recommended as an audiological management for the improvement of speech recognition in children with UCHL in classrooms. J. Med. Invest. 67 : 134-138, February, 2020.

Serum anti-p53 antibody is used clinically as a tumor marker of colorectal cancer. However, its prognostic significance in patients with metastatic colorectal cancer (mCRC) remains unclear. KRAS status may influence the host immune response against tumor progression. In the present study, we investigated the prognostic significance of serum anti-p53 in mCRC patients with wild-type KRAS and mutant KRAS treated with systemic chemotherapy. A retrospective study of 150 mCRC patients in whom serum anti-p53 antibody was measured before first-line chemotherapy was conducted. The patients were divided into two groups, high p53 and low p53, based on their serum anti-p53 antibody levels. Associations between serum anti-p53 level and clinical outcomes were evaluated in conjunction with KRAS status. There were 97 (64.7%) patients with wild-type KRAS and 53 (35.3%) with mutant KRAS. In an analysis of all patients, there was no significant difference in overall survival (OS) between the high p53 and low p53 groups. In patients with mutant KRAS, those in the high p53 group exhibited significantly longer OS than those in the low p53 group (p = 0.017, log-rank test). In the multivariate analysis, serum p53 antibody level was an independent predictor of OS in mCRC patients (high vs. normal; hazard ratio 0.438, 95% confidence interval 0.178–0.974, p

Background Systemic inflammation may influence the response to systemic chemotherapy or the prognosis in patients with various cancers. The Naples prognostic score, based on inflammatory and nutritional statuses, is a useful prognostic marker in patients undergoing surgery for colorectal cancer; however, its significance in patients with metastatic colorectal cancer remains unclear. Objective We aimed to evaluate the prognostic significance of the Naples prognostic factor in patients with metastatic colorectal cancer receiving first-line chemotherapy and to compare its prognostic accuracy with the neutrophil:lymphocyte ratio, platelet:lymphocyte ratio, and the systemic immune-inflammatory index. Design This was a retrospective study of prospectively collected data. Settings This study was conducted at a university hospital. Patients A total of 259 patients received first-line systemic chemotherapy for metastatic colorectal cancer. Main outcome measures The Naples prognostic score was calculated by a composite score of albumin and cholesterol concentrations, lymphocyte:monocyte ratio, and neutrophil:lymphocyte ratio. The patients were divided into 3 groups based on increasing Naples scores (groups 0-2), and the associations of the Naples prognostic score with clinicopathologic features and overall survival were evaluated. Results Higher Naples prognostic score was positively associated with right-sided primary tumors and synchronous metastases and negatively with primary tumor resection. Patients in group 2 (high Naples prognostic score) had significantly shorter overall survival than those in groups 0 and 1 (p = 0.012 and 0.022). Multivariate Cox regression analysis identified the Naples prognostic score as an independent prognostic factor for overall survival (HR = 1.574; p = 0.004). Time-dependent receiver operating characteristic curve analysis showed that Naples prognostic score was more sensitive than other prognostic factors for predicting overall survival. Limitations The main limitations are the sample size, single institutional feature, and treatment heterogeneity. Conclusions The Naples prognostic score may be a useful prognostic marker in patients with metastatic colorectal cancer receiving systemic chemotherapy. See Video Abstract at http://links.lww.com/DCR/B72. LA PUNTUACION PRONOSTICA DE NAPOLES ES UN MARCADOR PRONOSTICO UTIL EN PACIENTES CON CANCER COLORRECTAL METASTASICO: La inflamacion sistemica puede influir en la respuesta a la quimioterapia sistemica o el pronostico en pacientes con varios tipos de cancer. La puntuacion pronostica de Napoles, basada en estados inflamatorios y nutricionales, es un marcador pronostico util en pacientes sometidos a cirugia por cancer colorrectal; sin embargo, su importancia en pacientes con cancer colorrectal metastasico sigue siendo incierta.El objetivo fue evaluar la importancia pronostica del factor pronostico de Napoles en pacientes con cancer colorrectal metastasico que reciben quimioterapia de primera linea y comparar su precision pronostica con la relacion neutrofilos: linfocitos, plaquetas: linfocitos y el indice sistemico inmune-inflamatorio.Este estudio se realizo en un hospital universitario.Este fue un estudio retrospectivo de datos recolectados prospectivamente.Un total de 259 pacientes recibieron quimioterapia sistemica de primera linea para el cancer colorrectal metastasico.La puntuacion pronostica de Napoles se calculo mediante una puntuacion compuesta de concentraciones de albumina y colesterol, proporcion de linfocitos: monocitos y proporcion de neutrofilos: linfocitos. Los pacientes se dividieron en tres grupos basados en el aumento de las puntuaciones de Napoles (grupos 0-2, respectivamente) y se evaluaron las asociaciones de la puntuacion pronostica de Napoles con las caracteristicas clinico-patologicas y la supervivencia general.La puntuacion pronostica de Napoles es mas alta se asocio positivamente con los tumores primarios del lado derecho y metastasis sincronicas, y negativamente con la reseccion del tumor primario. Los pacientes del grupo 2 (alto puntaje pronostico de Napoles) tuvieron una supervivencia general significativamente menor que los de los grupos 0 y 1 (p = 0.012 y 0.022, respectivamente). El analisis de regresion de Cox multivariado identifico la puntuacion pronostica de Napoles como un factor pronostico independiente para la supervivencia global (indice de riesgo = 1.574; p = 0.004). El analisis de la curva caracteristica de funcionamiento del receptor dependiente del tiempo mostro que la puntuacion pronostica de Napoles era mas sensible que otros factores pronosticos para predecir la supervivencia global.Las principales limitaciones son el tamano de la muestra, la caracteristica institucional unica y la heterogeneidad del tratamiento.La puntuacion pronostica de Napoles puede ser un marcador pronostico util en pacientes con cancer colorrectal metastasico que reciben quimioterapia sistemica. Vea el Abstract del video en http://links.lww.com/DCR/B72.

Aims Numerous experimental studies have shown that cellular therapy, including human dental pulp stem cells (DPSCs), is an attractive strategy for ischemic brain injury. Herein, we examined the effects of intravenous DPSC administration after transient middle cerebral artery occlusion in rats. Methods Male Sprague-Dawley rats received a transient 90 min middle cerebral artery occlusion. DPSCs (1 × 106 cells) or vehicle were administered via the femoral vein at 0 h or 3 h after ischemia-reperfusion. PKH26, a red fluorescent cell linker, was used to track the transplanted cells in the brain. Infarct volume, neurological deficits, and immunological analyses were performed at 24 h and 72 h after reperfusion. Results PKH26-positive cells were observed more frequently in the ipsilateral than the contralateral hemisphere. DPSCs transplanted at 0 h after reperfusion significantly reduced infarct volume and reversed motor deficits at 24 h and 72 h recovery. DPSCs transplanted at 3 h after reperfusion also significantly reduced infarct volume and improved motor function compared with vehicle groups at 24 h and 72 h recovery. Further, DPSC transplantation significantly inhibited microglial activation and pro-inflammatory cytokine expression compared with controls at 72 h after reperfusion. Moreover, DPSCs attenuated neuronal degeneration in the cortical ischemic boundary area. Conclusions Systemic delivery of human DPSCs after reperfusion reduced ischemic damage and improved functional recovery in a rodent ischemia model, with a clinically relevant therapeutic window. The neuroprotective action of DPSCs may relate to the modulation of neuroinflammation during the acute phase of stroke.

Background and Purpose: We investigated whether the signal change on fluid-attenuated inversion recovery (FLAIR) can serve as a tissue clock that predicts the clinical outcome after endovascular thrombectomy (EVT), independently of the onset-to-admission time. Methods: Consecutive patients with acute stroke treated with EVT between September 2014 and December 2018 were enrolled. Based on the parenchymal signal change on FLAIR, patients were classified into FLAIR-negative and FLAIR-positive groups. The clinical characteristics, imaging findings, EVT parameters, and the intracranial hemorrhage defined as Heidelberg Bleeding Classification ≥1c hemorrhage (parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, and/or subdural hemorrhage) were compared between the 2 groups. A modified Rankin Scale score 0 to 1 at 3 months was considered to represent a good outcome. Results: Of the 227 patients with EVT during the study period, 140 patients (62%) were classified into the FLAIR-negative group and 87 (38%) were classified into the FLAIR-positive group. In the FLAIR-negative group, the patients were older ( P =0.011), the onset-to-image time was shorter ( P P =0.006), and the rate of intravenous thrombolysis was higher ( P P =0.173), the frequency of both any-intracranial hemorrhage and Heidelberg Bleeding Classification ≥1c hemorrhage were higher in the FLAIR-positive group ( P =0.004 and 0.011). At 3 months, the percentage of patients with a good outcome (FLAIR-negative, 41%; FLAIR-positive, 27%) was significantly related to the FLAIR signal change ( P =0.047), while the onset-to-image time was not significant ( P =0.271). A multivariate regression analysis showed that a FLAIR-negative status was independently associated with a good outcome (odds ratio, 2.10 [95% CI, 1.02–4.31], P =0.044). Conclusions: A FLAIR-negative status may predict the clinical outcome more accurately than the onset-to-admission time, which may support the role of FLAIR as a tissue clock.

Introduction The present study assessed the utility of a dry box time trial during laparoscopic surgical training to improve laparoscopic surgical skills and surgical outcomes. Methods In a monthly time trial, surgeon trainees twice completed a set task that involved grasping a suture, aligning a needle with a needle holder, passing the suture, making three knots, and cutting the two tails of the suture. The mean suturing time was then analyzed. To assess the utility of this time trial, we analyzed the short-term outcomes of patients with stage I to III colon cancer who had undergone laparoscopic colectomy before and after the introduction of the time trial. Results The monthly time trial was introduced in October 2018, and 52 surgeon trainees participated in the trials examined in this study. Within 6 months of the program's introduction, the mean suturing time had significantly declined to less than 70% of the time trial, while the standard deviations had declined to less than 30%. In comparisons of the short-term outcomes of laparoscopic colon cancer surgery before (n = 49) and after (n = 46) the introduction of the time trial, the operative time tended to decline (P = .074) after the introduction of the time trial, and blood loss was significantly reduced (P = .018). The rate of postoperative complications was similar before and after the introduction. Conclusion Regular time trials of laparoscopic surgical suture training using a dry box can be useful for improving laparoscopic surgical skills and surgical outcomes. Moreover, time trials can keep trainees motivated.

Liver fibrosis influences liver regeneration and surgical outcomes, and several noninvasive models based on laboratory data have been developed to predict liver fibrosis. This study was performed to determine whether the Fibrosis-4 (FIB-4) index, a noninvasive fibrosis marker, can predict the prognosis in patients with colorectal liver metastases (CRLM) undergoing hepatectomy. This retrospective study involved 193 consecutive patients with CRLM who underwent hepatectomy. The FIB-4 index was calculated by laboratory data and age before hepatectomy and before preoperative chemotherapy. The FIB-4 cut-off was determined using survival classification and regression tree analysis. Patients were divided into two groups (high and low FIB-4 index), and post-hepatectomy overall survival (OS) and recurrence-free survival (RFS) were investigated. In total, 193 patients were evaluated. Chemotherapy before hepatectomy was performed in 105 (54.4%) patients. A high FIB-4 index (> 2.736) was found in 39 (20.2%) patients. OS was significantly shorter in patients with a high FIB-4 index than those with a low FIB-4 index in the univariate (45.9 vs. 74.4 months, log-rank p = 0.007) and multivariate analysis (hazard ratio 2.28, 95% confidence interval 1.39–3.74; p = 0.001). Among patients who received chemotherapy before hepatectomy, those with a high FIB-4 index had significantly shorter RFS (6.9 vs. 45.3 months, log-rank p = 0.047) and OS (23.9 vs. 55.0 months, log-rank p = 0.003) than those with a low FIB-4 index. This association was also confirmed by multivariate analysis (hazard ratio 4.28, 95% confidence interval 1.46–12.6; p = 0.008). Both the preoperative and prechemotherapy FIB-4 index can predict long-term outcomes after hepatectomy in patients with CRLM.

Accumulating evidence suggests that the inflammatory tumor microenvironment can potentiate tumor progression and metastasis. The C-reactive protein-to-albumin ratio (CAR) is a novel inflammation-based prognostic score. This study was performed to examine the associations of the preoperative CAR with clinical outcomes in patients with colorectal liver metastases (CRLM) after curative resection.We retrospectively assessed the preoperative CAR in 184 patients who underwent curative resection for CRLM from November 2001 to January 2018 at Kumamoto University (Kumamoto, Japan). The optimal cutoff level of the preoperative CAR was determined by survival classification and regression tree (CART) analysis. We compared clinicopathological factors and prognoses between the high-CAR and low-CAR groups. A Cox proportional hazards model was used to calculate hazard ratios (HRs), controlling for potential confounders.A higher preoperative CAR was associated with worse overall survival (OS) (p 0.0001) and recurrence-free survival (RFS) (p = 0.003). Applying survival CART analysis, the high-CAR group comprised 33 patients (17.9%). In the multivariate analyses, a high CAR was independently associated with shorter OS (HR, 2.82; 95% confidence interval, 1.63-4.72; p = 0.0004) and RFS (HR, 1.62; 95% confidence interval, 1.02-2.49; p = 0.040). A high CAR was associated with a large tumor size, high serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels, high intraoperative blood loss, and more postoperative complications.A high preoperative CAR is associated with shorter OS and RFS and might serve as a prognostic marker for patients with CRLM after curative resection.

Objective We retrospectively evaluated the impact of postoperative complications on long-term outcomes after curative resection for colorectal cancer (CRC), using propensity-score analysis (PSA). Patients and methods We reviewed data from 673 consecutive patients with stage I to III CRC, who underwent curative resections between 2005 and 2017. Patients were divided into the complication group (Clavien-Dindo [CD] grade ≥ 3) and the control group (others). We performed PSA to obtain unbiased estimates of the effects of the oncological background on each outcome. Results We matched for sex, age, American Society of Anesthesiologists grade, location (right colon/left colon/rectum), histology (tub1/tub2/por), pathological tumor depth, and lymph node metastases. Eighty-five patients (12.6%) developed postoperative complications with CD grade ≥ 3. After PSA, 81 patients were included in each group. The complication group showed significantly worse relapse-free survival (RFS) than the control group (5-year RFS rate: 62% vs 77%; P = .047). In multivariate analysis with inverse probability of treatment weights, the complication group had a higher risk of relapse or death than the control group (hazard ratio: 2.08, 95% confidence interval:1.3-3.3; P = .018). Conclusions Postoperative complications (CD grade ≥ 3) could cause poor long-term outcomes in patients with stage I to III CRC; their presence requires appropriate adjuvant chemotherapy and follow-up.

Melinjo seed extract (MSE) contains large amounts of polyphenols, including dimers of trans-resveratrol (e.g. gnetin C, L, gnemonoside A, B and D), and has been shown to potentially improve obesity. However, there is no clinical evidence regarding the anti-obesity effects of MSE, and its mechanisms are also unclear. We investigated the hypothesis that MSE supplementation increases the adiponectin (APN) multimerization via the up-regulation of disulfide bond A oxidoreductase-like protein (DsbA-L) under either or both physiological and obese conditions. To investigate the effect of MSE on the physiological condition, 42 healthy young volunteers were enrolled in a randomized, double-blind placebo-controlled clinical trial for 14 days. The participants were randomly assigned to the MSE 150 mg/day, MSE 300 mg/day or placebo groups. Furthermore, in order to investigate the effect of MSE on APN levels under obese conditions, we administered MSE powder (500 or 1000 mg/kg/day) to control-diet- or high-fat-diet (HFD)-fed C57BL/6 mice for 4 weeks. All participants completed the clinical trial. The administration of MSE 300 mg/day was associated with an increase in the ratio of HMW/total APN in relation to the genes regulating APN multimerization, including DsbA-L. Furthermore, this effect of MSE was more pronounced in carriers of the DsbA-L rs191776 G/T or T/T genotype than in others. In addition, the administration of MSE to HFD mice suppressed their metabolic abnormalities (i.e. weight gain, increased blood glucose level and fat mass accumulation) and increased the levels of total and HMW APN in serum and the mRNA levels of ADIPOQ and DsbA-L in adipose tissue. The present study suggests that MSE may exert beneficial effects via APN multimerization in relation to the induction of DsbA-L under both physiological and obese conditions.

Background and Purpose— The strong evidence of endovascular therapy in acute ischemic stroke patients with large vessel occlusion (LVO) is revealed. Such patients are required to direct transport to the hospital capable of endovascular therapy. There are several prehospital scales available for paramedics to predict LVO. However, they are time consuming, and several of them include factors caused by other types than LVO. Therefore, we need a fast, simple, and reliable prehospital scale for LVO. Methods— We developed a new prehospital stroke scale, emergent large vessel occlusion (ELVO) screen, for paramedics to predict LVO. The study was prospectively performed by multistroke centers. When paramedics referred to stroke center to accept suspected stroke patients, we obtain the following information over the telephone. ELVO screen was designed focusing on cortical symptoms: 1 observation; presence of eye deviation and 2 questions; paramedics show glasses, what is this? and paramedics show 4 fingers, how many fingers are there? If the presence of eye deviation or ≥1 of the 2 items were incorrect, ELVO screen was identified as positive. We evaluated between results of ELVO screen and presence of LVO on magnetic resonance angiography at hospital arrival. Results— A total of 413 patients (age, 74±13 years; men, 234 [57%]) were enrolled. Diagnosis was ischemic stroke, 271 (66%); brain hemorrhage 73 (18%); subarachnoid hemorrhage, 7 (2%); and not stroke, 62 (15%). One hundred fourteen patients had LVO (internal carotid artery, 33 [29%]; M1, 52 [46%]; M2, 21 [18%]; basilar artery, 5 [4%]; P1, 3 [3%]). Sensitively, specificity, positive predictive value, negative predictive value, and accuracy for ELVO screen to predict LVO were 85%, 72%, 54%, 93% and 76%, respectively. Among 233 patients with negative ELVO screen, only 17 (7%) had LVO, which indicated to be an ideal scale to avoid missing endovascular therapy. Conclusions— The ELVO screen is a simple, fast, and reliable prehospital scale for paramedics to identify stroke patients with LVO for whom endovascular therapy is an effective treatment.

Perampanel (PER), a noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor antagonist, clinically used for seizure control, has been reported to exert neuroprotective effects in experimental models of neurodegenerative diseases. However, few studies have investigated the therapeutic effects of PER in brain injury including stroke. Our aim was to investigate the neuroprotective potential of PER using a rat transient middle cerebral artery occlusion (MCAO) model. Sprague-Dawley rats underwent 90-min MCAO followed by intraperitoneal PER administration at a dose of 1.5 mg/kg. Infarct volumes, neurological deficits, and immunological analyses were performed at 7 days after MCAO. PER significantly reduced infarct volumes (p 0.05) and improved motor function (p 0.05) compared with vehicle. Immunological analysis showed that PER significantly inhibited microglial activation, pro-inflammatory cytokine expression, and oxidative stress compared with vehicle. Moreover, PER suppressed neurodegeneration in the cortical ischemic boundary zone, via downregulation of Bcl-2-associated x and upregulation of Bcl-extra-large with Akt activation. In addition, post-stroke secondary neuronal damage and cognitive impairments, using the Y-maze test, were assessed 30 days after MCAO. PER significantly improved spatial working memory, which was accompanied by hippocampal CA1 neuronal loss and cortical thinning, compared with vehicle. These results indicate that PER attenuates infarct volumes and motor function deficits possibly through its anti-inflammatory, antioxidant, and anti-apoptotic activities, mediated via activation of phosphatidylinositol 3-kinase (PI3K)/Akt pathways in the acute ischemic phase, and further ameliorates post-stroke cognitive impairments via the suppression of secondary neuronal damage in the chronic ischemic phase.

BACKGROUND/AIM The Controlling Nutritional Status (CONUT) score is a useful nutritional evaluation, that is calculated from serum albumin, total cholesterol concentrations, and total lymphocyte count. This study aimed to investigate the association between the CONUT score and prognosis in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS The CONUT score was retrospectively calculated in 211 patients with mCRC receiving first-line chemotherapy. The patients were divided into three groups: the CONUT low-group (0-1), intermediate-group (2-4), and high-group (5-). The associations of the CONUT score with clinicopathological factors and survival outcomes were evaluated. RESULTS The higher CONUT score was significantly associated with synchronous metastases, and no primary tumor resection. The higher CONUT score group showed a significant shorter progression-free survival (log-rank p

Anemia upon hospital admission is a known predictor of poor functional outcomes in patients with acute cerebral infarction. However, it remains unclear whether reductions in hemoglobin levels during hospitalization influence stroke outcomes. We investigated the association between in-hospital decline in hemoglobin and poor outcomes.We retrospectively analyzed data from 480 consecutive patients who had experienced acute cerebral infarction and presented without anemia between January 2012 and March 2015. Decline in hemoglobin was taken as the difference between hemoglobin levels upon admission and nadir hemoglobin. Poor outcome was defined as a modified Rankin Scale score 3-6. A multivariate analysis of the relationship between decline in hemoglobin and poor outcome at discharge was conducted for various patient characteristics.The mean hemoglobin level at admission was 14.3 ± 1.3 g/dL, whereas the mean nadir hemoglobin value was 13.1 ± 1.9 g/dL, with a mean decline in hemoglobin of 1.3 ± 1.5 g/dL. In patients with poor outcomes, mean decline in hemoglobin was significantly reduced to 3.1 g/dL (P .001). The optimal cutoff decline in hemoglobin required to distinguish a poor outcome was 1.5 g/dL whereas the sensitivity and specificity were 62% and 82.3%, respectively, with an area under the curve of .77 (P .0001). A decline in hemoglobin below 1.5 g/dL was found to be an independent predictor of poor outcome (odds ratio: 2.10; confidence interval: 1.10-3.99; P = .023).Decline in hemoglobin in patients hospitalized with acute stroke may be associated with poor outcome.

Background Poststroke infection (PSI) is common and is usually associated with a severe prognosis. We investigated the association between PSI and thyroid hormones, which are critical to immune regulation, in patients with acute stroke. Methods We retrospectively enrolled 520 consecutive patients with acute ischemic stroke (326 men; age, 71.9 ± 13.2 years) admitted to our department between September 2014 and June 2016. The impact of serum thyroid hormone levels measured at admission (thyroid-stimulating hormone [TSH], free triiodothyronine [FT3], and free thyroxine [FT4]) on the PSI was evaluated using multivariate logistic regression analysis. Results We diagnosed 107 patients (20.6%; pneumonia, 65; urinary tract infection, 19; others, 23) with PSIs. While age ( P .001), body mass index ( P = .0012), preadmission modified Rankin scale score ( P = .0001), National Institutes of Health Stroke Scale score on admission ( P .001), admission FT3 level ( P .001), atrial fibrillation ( P .001), and ischemic heart disease ( P = .0451) were significantly associated with PSI, we found no relationship among TSH levels, FT4 levels, and PSI occurrence. After multivariate adjustment, patients with PSIs were more frequently in the Q1 quartile (≤2.25 pg/mL) than in the Q2 (2.26-2.55 pg/mL; P = .0251), Q3 (2.56-2.89 pg/mL; P = .0007), or Q4 (≥2.90 pg/mL; P = .0010) quartiles of FT3 levels. Moreover, low FT3 levels ( P = .0013). Conclusions Low FT3 levels at admission are independently associated with PSI occurrence.

Background: It is unknown whether the effect of onset-­­to-door (OTD) time on clinical outcomes differs between ­patients with and without large artery occlusion (LAO) who undergo hyperacute recanalization therapy. Methods: Hyperacute recanalization therapy includes intravenous thrombolysis tissue-plasminogen activator (tPA), and endovascular therapy (EVT). Favorable clinical outcome was defined as modified Rankin Scale of ≤2 at discharge. Results: Among 164 patients, 117 (71%) patients received tPA, 86 (52%) received EVT, and 39 (24%) received tPA and EVT. One hundred and fifteen patients (70%) were classified into the LAO group and 49 (30%) into the non-LAO group. In the total cohort, multivariate regression analysis showed OTD time (OR 0.809 [95% CI 0.693–0.944], p = 0.007) was an independent factor related to the favorable outcome. Similarly, among patients with LAO, OTD was an independent negative factor for the favorable outcome (0.779 [0.646–0.940], p = 0.009). On the contrary, OTD was not associated with the favorable outcome (1.5 [0.7–2.5] vs. 1.7 [1.1–3.2], p = 0.155) in patients without LAO. This was confirmed with multivariate regression analysis, which did not show OTD to be an independent factor for the favorable outcome (0.900 [0.656–1.236], p = 0.516). Conclusion: The effect of early hospital arrival on clinical outcome differed between patients with and without LAO.

Stroke-associated infection (SAI) is a common and serious complication of stroke. This study aimed to assess the effects of SAI on patient mortality and functional outcome at 3 months after stroke onset. We retrospectively analyzed 809 consecutive patients with acute stroke (517 men and 292 women; median age, 72 years) who were admitted to our department between September 2014 and June 2016. SAI was defined as an infection diagnosed during the hospitalization period. Poor outcome was defined as a modified Rankin Scale (mRS) score of 3-5 or death (mRS score of 6). The effect of SAI on functional outcome was evaluated using a multivariate logistic regression analysis. SAI occurred in 169 patients (20.9%); of these, 106 (62.7%) had pneumonia, 23 (13.6%) had a urinary-tract infection, and 40 (23.7%) had other types of infection. Patients with SAI were older, more likely to be female, had lower body mass indices, had higher stroke severity, and were more likely to have atrial fibrillation and a history of ischemic heart disease than patients without SAI. Poor functional outcome and mortality were more common in patients with SAI than in patients without SAI (poor functional outcome 41.8 vs. 4.8%, mortality 24.3 vs. 3.9%, respectively). After adjusting for age, sex, stroke severity, and various comorbidities, SAI was independently associated with poor functional outcome [odds ratio (OR) 6.88; 95% confidence interval (CI) 3.72-12.73] and mortality (OR 4.45, 95% CI 2.27-8.72) at 3 months after stroke onset. Our results suggest that SAI during the hospitalization period is independently associated with 3-month poor functional outcome and mortality.

Background and Purpose Recent studies using magnetic resonance imaging (MRI) have reported that wake-up stroke (WUS) patients may be able to be treated using tissue-plasminogen activator (tPA) when showing no ischemia on fluid-attenuated inversion recovery (Negative-FLAIR). We investigated the frequency of WUS and calculated what percentage of WUS patients with Negative-FLAIR meets most of the conventional tPA criteria. We did not include a time parameter in this study. Methods Consecutive patients with acute stroke affecting the anterior circulation who presented within 12 h of onset were enrolled. All patients were examined using diffusion-weighted imaging (DWI) and FLAIR. As large infarctions are excluded from tPA therapy, an Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS) of ≤ 3 was used as the upper limit for exclusion. Results A total of 816 consecutive patients were included in the study and were separated into two groups; 163 (20%) WUS patients as the WUS group, and 653 (80%) non-WUS patients as the non-WUS group. The median National Institutes of Health Stroke Scale (NIHSS) score on admission was 7 (interquartile range, 3–17) in the WUS group and 8 (3–16) in the non-WUS group (p = 0.313). MRI study revealed Negative-FLAIR in 67 (41%) of 163 patients in the WUS group. Of the 67 patients with Negative-FLAIR, 19 patients were excluded from tPA therapy. Therefore, 48 (29%) of the 163 wake-up stroke patients met the tPA criteria. Conclusions About 30% of WUS patients may be candidates for tPA therapy based upon Negative-FLAIR findings.

Cortical superficial siderosis (cSS) is a pathologic and radiologic diagnosis of hemosiderin deposition in subpial brain layers. However, cSS has not been fully studied in patients with acute stroke. Here, we investigated the prevalence of cSS in patients with acute stroke and analyzed the relationship between cSS and different clinical and neuroimaging characteristics. From September 2014 through June 2016, consecutive patients with acute stroke who were admitted to our department were retrospectively investigated. We analyzed the prevalence of cSS and the associations between cSS and risk factors, the topographic distribution of cerebral microbleeds (CMBs), and the severity of white matter lesions (WMLs). In total, 739 patients (589 patients with ischemic stroke/transient ischemic stroke [IS/TIA] and 150 with intracerebral hemorrhage [ICH]; mean age, 71.4 years) were enrolled. We identified cSS in six (1.0%) patients with IS/TIA and seven (4.7%) patients with ICH. The presence of cSS was associated with ICH (P

Recently, adipose tissue has been regenerated by combining scaffolds, growth factors, and/or adipose tissue-derived stromal cells (ASCs). However, the safety of growth factors and ASCs has not been confirmed in cancer patients. We reported the regeneration of adipose tissue in the internal space of a polypropylene mesh containing a collagen sponge (CS), without using any growth factors or cells. We herein explored the formation of adipose tissue, using the bioabsorbable implant containing CS, in rats. We prepared the implants without and with CS, using threads of either poly l-lactide-co-e-caprolactone [P(LA/CL)] or poly-l-lactic acid (PLLA), and measured their strengths. The procedure was performed in the rat inguinal region. In the control group, no operative procedure was performed. In the sham-operation group, skin incision without implantation was performed. The other groups received CS alone and the two implants with and without CS, respectively. The areas of formed tissue and adipose tissue inside the implants and the remnants of CS were evaluated. All implants maintained the internal space before implantation. At 6 and 12 months post-implantation, the internal space was maintained and the formation of adipose tissue was promoted in the two PLLA groups. At 6 months, the internal space was maintained and more adipose tissue was formed in the PLLA with CS group than in the PLLA group. Porcine collagen was absorbed within 3 months. The PLLA implant with CS is a novel bioabsorbable implant that is replaced with autologous adipose tissue after implantation.

Background: Thrombus visualization in patients with acute ischemic stroke has been detected and reported using various imaging modalities. T1-weighted imaging (T1-WI) can depict thrombi as hyperintense signals within vessels. Moreover, in addition to thrombi, T1-WI hyperintensities in arteries may suggest arterial dissection. However, the frequency of and factors related to the T1-hyperintense vessel sign (T1-HVS) are not fully known. The aim of this study was to clarify the prevalence of and related factors for the T1-HVS in patients with acute ischemic stroke. Methods: From September 2014 through December 2015, consecutive acute ischemic stroke patients who were admitted to our stroke unit within 7 days from symptom onset were retrospectively recruited from the prospective registry. A T1-HVS was defined as the presence of a hyperintense signal, with intensity higher than surrounding brain, within the vessel lumen. Moreover, T1-HVSs were separated into filled T1-HVSs (hyperintensity fills whole vessel lumen) and non-filled T1-HVSs. The frequency of the T1-HVS and the timing of emersion and the relationship between the presence of the T1-HVS and arterial occlusion were assessed. Results: A total of 399 patients (139 women; median age 73 years; National Institutes of Health Stroke Scale score 3) were enrolled in the present study. Of these, 327 (82%) patients had T1-WI on admission. Two hundred and sixty-seven (67%) subjects had at least one follow-up T1-WI (median 6 days after admission), and 134 (34%) cases had ≥2 follow-up T1-WI examinations. The T1-HVS was observed in 18 patients during admission; therefore, the frequency of the T1-HVS in acute ischemic stroke patients was 4.5% (95% CI 2.5-6.5%). All but one (94%) of the T1-HVSs were first observed on follow-up imaging, and the median number of days from onset to T1-HVS appearance was 9. For patients having initial major artery occlusion and follow-up MRI (n = 95), sensitivity and specificity of the T1-HVS for persistent arterial occlusion on follow-up MR angiography were 22 and 100%, respectively. T1-HVS persisted for a few months and then normalized. Although there were no significant differences between filled and non-filled T1-HVS, more patients with non-filled T1-HVS had arterial dissection (43%) than those with filled T1-HVS (9%, p = 0.245). Conclusion: The T1-HVS was observed in 4.5% of acute ischemic stroke patients. T1-HVSs appeared in the subacute phase in arteries with persistent occlusion and remained for a few months.

Objective This study was performed to investigate whether the Penumbra 5MAX ACE is superior to other Penumbra systems. Materials and Methods We performed a retrospective, single center analysis of patients with acute ischemic stroke with occlusion of the internal carotid artery or middle cerebral artery (M1 segment) who underwent endovascular therapy using a Penumbra system. The reperfusion success rate, puncture-to-revascularization time, and number of passes were assessed. Multivariate regression analysis was conducted to evaluate independent factors related to revascularization within 60 minutes. Successful revascularization was defined by a thrombolysis in cerebral infarction score ≥2b. Results The Penumbra 5MAX ACE was used in 24 of the 40 patients (60%). Although the revascularization success rate was similar between patient groups ( P = .229), the number of passes was significantly lower (1.5 ± .8 versus 2.6 ± 1.3, P = .006) and the puncture-to-revascularization time was shorter (50 ± 26 minutes versus 116 ± 69 minutes, P = .002) in patients treated with the Penumbra 5MAX ACE. The Penumbra 5MAX ACE was identified as an independent factor for early revascularization (odds ratio, 5.80; P = .041). Among patients with a premorbid modified Rankin Scale score of 0-1, a modified Rankin Scale score of 0-2 at 3 months was observed in 15 of the 19 patients (79%) treated with the Penumbra 5MAX ACE and in 8 of the 16 (50%) who were not ( P = .072). Conclusion Acute revascularization therapy using the Penumbra 5MAX ACE can achieve rapid successful recanalization and tend to improve clinical outcomes.

Magnetic resonance imaging (MRI) has recently emerged as a first-line tool for investigating acute stroke. However, MRI requires long scan times, which could be detrimental for severe stroke patients with a large intracerebral hemorrhage (ICH). MRI scout images, which are taken prior to a study to determine the range of subsequent images, can be used to rapidly screen the whole brain. We examined whether MRI scout imaging can detect ICHs observed by computed tomography (CT).Between September 2014 and March 2016, consecutive acute ICH patients who underwent both MRI scout and CT imaging in the acute setting were studied. ICHs on MRI scout images were defined as space-occupying lesions. Two neurologists independently assessed the scout images. We investigated whether ICHs on CT scans can be detected on MRI scout images and the characteristics of ICHs not detected by MRI scout images.One hundred and forty-eight ICH patients (median age, 68 [interquartile range, 59-77] years; 99 [67%] males; median National Institutes of Health Stroke Scale score, 11 [4-17]) were enrolled. Among these, 138 (93%) patients were diagnosed as having ICH by MRI scout imaging (positive group), and 10 (7%) patients were not (negative group). The bleeding volume was 9.3 [4.5-22.4] ml in the positive group and 1.0 [0.4-2.0] ml in the negative group (p .001). The cut-off value of bleeding volume calculated from the receiver operating characteristic curve was 2.0 ml. Regarding ICH lesions, 4 (44%) of the 9 pontine hemorrhages were detected on MRI scout images, whereas 134 (96%) of the 139 other hemorrhages were diagnosed (p .001).We diagnosed90% of ICHs using MRI scout images. Low levels of ICH and pontine hemorrhaging might be difficult to detect using MRI scout imaging.

Cognitive assessment is not performed routinely in the acute stroke setting. We investigated factors associated with cognitive impairment and the differences between the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores in patients with acute stroke.In this prospective study, 881 consecutive patients (median age, 73 years) with acute stroke were enrolled. Clinical characteristics, such as education, vascular risk factors, premorbid cognitive status using the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), and stroke severity, were assessed. Cognitive performance was measured using MMSE and MoCA within 5 days of stroke onset.Both MMSE and MoCA were feasible in 621 (70.5%) patients. Factors independently associated with nonfeasibility were age (odds ratio [OR]: 1.05; 95% confidence interval [CI]: 1.02-1.08), IQCODE score (OR: 1.02; 95%CI: 1.00-1.04), and National Institutes of Health Stroke Scale (NIHSS) score (OR, 1.16; 95%CI, 1.12-1.20). Impaired MoCA (with a cut-off26/30) performance was observed in 544 of 621 (87.6%) patients. Factors independently associated with cognitive impairment were age (OR: 1.06; 95%CI: 1.03-1.10) and NIHSS score (OR: 1.34; 95%CI: 1.14-1.57). Eighty percent of patients with normal MMSE scores had an impaired MoCA score (MMSE-MoCA mismatch). The differences were highest in the visuospatial (94.8% versus 65.3%; P.0001), recall (76.6% versus 35.6%; P.0001), abstraction (82.5% versus 49.8%; P.0001), and language (72.3% versus 65.9%; P.0001) domains between the normal MMSE and MoCA group and MMSE-MoCA mismatch group.The MoCA can be particularly useful in patients with cognitive deficits undetectable on the MMSE in the acute stroke phase.

Adipose tissue regeneration in breast cancer patients without additional growth factors or adipose-tissue-derived stromal cells is desirable because of the possibility of recurrence and metastasis. We report that a poly-L-lactic acid (PLLA) mesh implant containing a collagen sponge (CS) maintained the internal space in vivo for up to 12 months and substituted for adipose tissue. We developed a PLLA capsule that maintained the internal space longer than that of PLLA mesh and compared adipose tissue formation at 12 and 24 months after implantation between the PLLA mesh with CS implant and the PLLA capsule implant with or without CS in a rabbit model. After 12 months, all implants maintained the internal space, and the adipose tissue that formed in all implant groups was larger than that in the control group. At 24 months, PLLA mesh maintained the internal space just as well as that at 12 months, while the PLLA capsule collapsed and accumulated a large number of macrophages. The formed adipose tissue in the PLLA mesh group was maintained up to 24 months; however, those in two PLLA capsule groups decreased and showed no difference from the control group. In conclusion, the internal space of the PLLA mesh implant with CS was substituted for adipose tissue at 12 months and sustained the formed adipose tissue after 24 months. The PLLA mesh implant containing CS is a desirable bioabsorbable implant that can be replaced by autologous adipose tissue after implantation in vivo without using any growth factors or cells.

Background The aim of the present study was to investigate the efficacy and safety of antiplatelet (aspirin plus cilostazol) dual therapy for patients with noncardioembolic stroke within 48 hours of symptom onset. Methods and Results The ADS (Acute Aspirin Plus Cilostazol Dual Therapy for Non‐Cardiogenic Stroke Patients Within 48 Hours of Symptom Onset ) study is an investigator‐initiated, prospective, multicenter (34 hospitals in Japan), randomized, open‐label, and aspirin‐controlled trial. Acute stroke patients with noncardioembolic stroke within 48 hours of onset were studied. The subjects were randomly allocated to combination therapy with aspirin 81 to 200 mg plus cilostazol 200 mg (dual group) and single therapy with aspirin 81 to 200 mg (aspirin group) for 14 days. After the 14 days, all patients took the cilostazol 200 mg for 3 months. A primary efficacy outcome was defined as any one of the following occurring (neurological deterioration, symptomatic stroke recurrence, or transient ischemic attack) within 14 days. A primary safety outcome included intracerebral hemorrhage and subarachnoid hemorrhage. Between May 2011 and June 2017, 1201 patients (796 [66%] men; median age, 69 [61–77] years) randomized 1:1 to either the dual group or the aspirin group were analyzed. Initial National Institutes of Health Stroke Scale score was 2 (1–4) in both groups ( P =0.830). A primary efficacy outcome was observed in 11% in the dual group and 11% in the aspirin group ( P =0.853). A primary safety outcome occurred in 2 (0.3%) in the dual group and in 1 (0.2%) in the aspirin group ( P =0.624). Conclusions Dual antiplatelet therapy using cilostazol and aspirin was safe but did not reduce the rate of short‐term neurological worsening. Clinical Trial Registration URL : umin.ac.jp/ctr/index/htm. Unique identifier: UMIN 000004950.

Background Catheter ablation (CA) has been reported to reduce risk of stroke in patients with nonvalvular atrial fibrillation (NVAF) in retrospective studies. However, the risks and benefits of CA have not been well elucidated in patients with NVAF and who have suffered a recent ischemic stroke in prospective randomized trials. Thus, the aim of the STABLED clinical trial is to investigate the efficacy and safety of CA with anticoagulant therapy using edoxaban in patients with NVAF and a history of recent ischemic stroke. Methods and design The STABLED trial is a multicenter, prospective, randomized, open-label, standard medication-controlled study in Japan. The target patient number is 250, comprising 125 patients receiving standard medication and 125 receiving CA. For patients allocated to the CA group, ablation is to be performed between 1 to 6 months from the onset of index stroke. The observation period will be 3 years from the day of random allocation of the final patient to any of the groups. The primary outcome measure is the composite of recurrence of ischemic stroke, systemic embolism, all-cause death, and hospitalization for heart failure. Conclusion This study will investigate the effectiveness and safety of CA and basic anticoagulation treatment with edoxaban for patients with NVAF who have suffered a recent ischemic stroke. The aim is to determine the best evidence for an optimal treatment strategy for patients with NVAF and recent stroke. Trial registration: UMIN000031424/ NCT03777631 .

Dopamine transporter (DAT) imaging such asWe studied 99 subjects, including 39 patients with Alzheimer's disease (AD), 15 patients with Parkinson's disease (PD) and 10 patients with dementia with Lewy bodies (DLB). Each subject had undergoneThe SBR with TM was 0.53 percentage points lower than the SBR without TM overall (p 0.01). Positive and negative reversal of AI increased with age. The rate of the SBR change with TM was tended to be lower in groups with brain atrophy. The number of voxels excluded by TM in striatal volumes of interest (VOIs) was larger with high groups for EI, SI and CAI than in low groups. The number of voxels excluded using TM in reference VOIs was related to SI.The SBR was decreased using TM. The effect of TM on the SBR tended to be small in the subjects with severe brain atrophy. The effect of brain atrophy in the TM is larger in the striatal VOIs than in the reference VOIs. Even if quantitative analyses are available, visual assessment of

Background We aimed to clarify associations between prior anticoagulation and short‐ or long‐term clinical outcomes in ischemic stroke or transient ischemic attack patients with nonvalvular atrial fibrillation. Methods and Results A total of 1189 ischemic stroke or transient ischemic attack patients with nonvalvular atrial fibrillation who were hospitalized within 7 days after onset were analyzed. Of these, 813 patients (68.4%) received no prior anticoagulation, 310 (26.1%) received prior warfarin treatment with an international normalized ratio ( INR ) INR ≥2 on admission, and the remaining 38 (3.2%) received prior direct oral anticoagulant treatment. Prior warfarin treatment was associated with a lower risk of death or disability at 3 months compared with no prior anticoagulation ( INR P =0.001; INR ≥2: adjusted odds ratio: 0.40; 95% CI, 0.16–0.97; P =0.043) but was not associated with a lower risk of death or disability at 2 years. Prior warfarin treatment with an INR ≥2 on admission was associated with a higher risk of ischemic events within 2 years compared with no prior anticoagulation (adjusted hazard ratio: 2.94; 95% CI, 1.20–6.15; P =0.021). Conclusions Prior warfarin treatment was associated with a lower risk of death or disability at 3 months but was not associated with a lower risk of death or disability at 2 years in ischemic stroke or transient ischemic attack patients with nonvalvular atrial fibrillation. Prior warfarin treatment with an INR ≥2 on admission was associated with a higher risk of ischemic events within 2 years. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01581502.

Background Anticoagulant therapy often requires temporary interruption. Nevertheless, the frequency and clinical characteristics of stroke patients who develop stroke during anticoagulant interruption are not fully known. Methods From March 2011 through May 2017, consecutive acute ischemic stroke patients with AF who were admitted to our stroke unit were retrospectively recruited. Patients who developed ischemic stroke during anticoagulant interruption were defined as those who developed ischemic stroke within 30 days from anticoagulant interruption. The frequency and clinical characteristics of patients during anticoagulant interruption were analyzed. Results A total of 561 patients with AF and acute ischemic stroke (237 women; median age 78 [IQR 71–85] years) were admitted during the study period. Of these, 21 (3.7%, 12 patients discontinued vitamin K antagonist [VKA] and 9 discontinued direct oral anticoagulants [DOACs]) patients were admitted during the period of anticoagulant interruption. Severity and functional outcomes in stroke patients during anticoagulant interruption were not different from those without anticoagulant treatment. The number of days between anticoagulant interruption and stroke onset was shorter in patients who discontinued DOACs (3 [3–5] days) than in those who discontinuedVKAs (10 [7–20] days, p = .004). The major reason for interruption was planning of invasive procedures (52%). Guideline deviations were suspected in 82% of such cases. Conclusion Patients developing stroke during anticoagulant interruption accounted for 3.7% of stroke patients with AF. Strokes occurred relatively early after interruption, especially in patients who discontinued DOACs. Guideline deviations was frequent.

BACKGROUND Because the efficacy and safety of anticoagulant therapy in patients with acute intracerebral hemorrhage (ICH) are not fully known, present study aimed to elucidate the current status and the safety of anticoagulant therapy, mainly direct oral anticoagulants (DOACs), for acute ICH and anticoagulant-indicated patients. Methods and Results: From September 2014 through March 2017, consecutive patients with acute (

Background and Purpose: Acute Stanford type A aortic dissection (AAD) is a devastating aortic disease, and prompt diagnosis is sometimes difficult to make. Identification of AAD in suspected acute stroke patients is especially challenging. Nevertheless, the frequencies and predictive factors of AAD in suspected acute stroke patients have not been well investigated. The aim of this study was to elucidate the prevalence of and predictors for AAD in patients with suspected acute stroke. Methods: From January 2012 through January 2013, consecutive patients who visited our emergency department (ED) due to suspected acute (Results: A total of 1,637 patients were included in this study. Five patients (0.31%, 95% CI 0.04-0.57) were diagnosed as having AAD. The prevalence of AAD in all AIS individuals during the study period was 1.09% (95% CI 0.14-2.05), and AAD accounted for 1.70% (95% CI 0.05-3.36) of AIS patients who appeared at the hospital within 4 h from onset. Most AAD patients presented with disturbed consciousness, and none of the AAD patients complained of chest pain. Neck ultrasonography detected an intimal flap in AAD patients. Two AAD cases died soon after ED arrival. The remaining 3 were promptly diagnosed as having AAD in the ED and underwent emergency surgery; all were discharged with only mild neurological symptoms. Low SBP in the right arm (cut-off value ≤110 mm Hg, sensitivity 100%, specificity 94.4%) and high D-dimer level (cut-off value ≥5.0 μg/ml, sensitivity 100%, specificity 91.7%) had high predictive values for detecting AAD in patients with AIS presenting within 4 h from onset. Conclusions: AAD was seen in 0.31% of suspected acute stroke patients and 1.70% of AIS patients presenting within 4 h from onset. AAD patients who were initially suspected as having acute stroke had severe neurological symptoms, including disturbance of consciousness, did not complain of typical chest pain, and when emergency surgery was performed, favorable neurological and survival outcomes were achieved. Low SBP in the right arm and high D-dimer level could predict AAD.

The objective of this study was to investigate the effects of latent TGF-β binding protein 4 (LTBP-4) on elastic fiber regeneration in three-dimensional cultures of human dermal fibroblasts (HDFs). Appropriate collagen scaffold for elastic fiber regeneration was also examined. Collagen sponges cross-linked at 120 °C and composed of small pores (25 μm on average) was favorable for elastic fiber regeneration by HDFs. Addition of LTBP-4, followed by culture for 21 days, accelerated elastic fiber accumulation within the scaffolds. Conditioned scaffolds containing either HDFs or LTBP-4-built mature elastic fibers were implanted between the dermis and the cutaneous muscle of mice. The combined use of HDFs and LTBP-4 resulted in thicker tissues containing elastic fibers. These results indicate that weakly cross-linked collagen sponges can be used as scaffolds for regenerating elastic fibers both in vitro and in vivo, and that the addition of LTBP-4 accelerates the deposition of both elastin and fibrillin-1, and increases cell proliferation. These techniques may be useful for generating cutaneous or cardiovascular tissue equivalents; furthermore, they may serve as a useful method for the three-dimensional analyses of drugs used to treat skin diseases or to examine the microstructure of elastin networks.

Ataxic hemiparesis (AH) is a classic lacunar syndrome associated with localized damage to the pons, internal capsule, thalamus, or corona radiata. A depression of metabolic activity known as crossed cerebellar diaschisis (CCD) is frequently observed in the cerebellar hemisphere contralateral to the site of the lesion in patients with AH. Though small cortical or subcortical lesions may result in AH, such occurrences are rare. The current report details the case of a patient with AH resulting from acute infarction associated with localized lesions of the postcentral gyrus who presented without CCD.

The long-term outcome in acute stroke patients with large vessel occlusion (LVO) treated with endovascular therapy (EVT) are unclear. We investigated functional outcomes one year after EVT in acute stroke patients with LVO.We retrospectively enrolled 149 stroke patients with LVO who underwent EVT from our prospective stroke registry. We assessed modified Rankin Scale (mRS) scores at one year from onset. The degree of recanalization was evaluated using modified thrombolysis in cerebral infarction (mTICI) grades. Good recanalization and a favorable outcome were defined as an mTICI grade ≥ 2b and mRS score ≤ 2, respectively.Favorable outcomes were observed in 76 (51.0%) patients. The favorable outcome group was younger (median age: 72 [interquartile range, 63-79] years vs. 79 [70-84] years, P .001) and had more male patients (79% vs. 60%, P = .013), lower National Institutes of Health Stroke Scale scores at admission (median 14 [7-18]) vs. 19 [15-25], P .001), higher DWI-ASPECTS upon admission (median [6-9] vs. 6 [4-8], P = .022), more patients with mTICI ≥ 2b (93% vs. 64%, P .001) and fewer post-therapy intracranial cerebral hemorrhages (13% vs. 29%, P = .019) than the poor outcome group. In our multivariate analysis, mTICI ≥ 2b were independently associated with favorable outcomes at one year from onset (odds ratio, 10.282; 95% confidence interval, 1.587-66.604; P = .015).Good recanalization was associated with favorable functional outcomes one year after EVT in acute stroke patients with LVO.

Objectives: Evaluation of cognitive status is not performed routinely in the acute stroke setting. This study aimed to evaluate the frequency of early cognitive impairment in patients with minor ischemic stroke, analyze the factors associated with early cognitive impairment, and assess functional outcomes. Methods: In this prospective study, 112 consecutive patients with acute minor ischemic stroke were enrolled. Neuroimages were assessed for semiquantitative evaluation of brain atrophy and small vessel disease (SVD) markers. Cognitive performance was measured within 5 days of onset using Montreal Cognitive Assessment (MoCA) scores. Functional outcome analyses were adjusted for demographic variables, premorbid cognitive status, education level, vascular risk factors, neuroimaging characteristics, stroke severity, and MoCA scores. Results: The median MoCA score was 22, and 63% of patients had cognitive impairment. Factors independently associated with cognitive impairment were education (odds ratios [OR], .79; confidence intervals [CI], .63-.99), smoking (OR, .26; 95%CI, .073-.89), and temporal horn atrophy (OR, 4.73; 95% CI, 1.66-13.49). Factors independently associated with poor functional outcome were total MoCA score (OR, .78; 95%CI, .62-.95) and the sum of 4 MoCA subscores (visuospatial/executive, attention, language, and orientation; OR, .72; 95%CI, .53-.92). The cutoff value of the sum of 4 MoCA subscores for predicting poor outcome was 13 points with 76.5% sensitivity and 81.1% specificity. Conclusions: Early cognitive impairment was common after minor ischemic stroke and was associated with preexisting temporal horn atrophy but not SVD markers. The sum of 4 MoCA subscores was useful in predicting the functional outcome.

Oxidative stress and inflammation play a key role in the age-related decline in the respiratory function. Adipokine in relation to the metabolic and inflammatory systems is attracting growing interest in the field of respiratory dysfunction. The present clinical and experimental studies investigated the role of the disulfide bond-forming oxidoreductase A-like protein (DsbA-L) gene, which has antioxidant and adiponectin multimeric (i.e. activation) properties, on the respiratory function of the elderly. We performed a retrospective longitudinal genotype-phenotype relationship analysis of 318 Japanese relatively elderly participants (mean age ± standard deviation: 67.0 ± 5.8 years) during a health screening program and an in vitro DsbA-L knock-down evaluation using 16HBE14o-cells, a commonly evaluated human airway epithelial cell line. The DsbA-L rs1917760 polymorphism was associated with a reduction in the ratio of forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) and %FEV1 and with the elevation of the prevalence of FEV1/FVC DsbA-L knock-down induced oxidative stress and up-regulated the mucus production in human airway epithelial cells. These findings suggest that the DsbA-L gene may play a role in protecting the respiratory function of the elderly, possibly via increased systemic adiponectin functions secreted from adipocytes or through systemic and/or local pulmonary antioxidant properties.

Background Atrial fibrillation (AF) is the leading cause of cardioembolic stroke (CES), and patients with stroke and AF are frequently assumed to have CES. However, strokes presumably due to atherosclerotic pathophysiologies in large or small vessels can also occur in patients with AF. The aims of the present study were to clarify the prevalence of and factors related to a non-cardioembolic etiology in acute stroke patients with AF. Methods From March 2011 through May 2017, consecutive acute ischemic stroke patients with AF were retrospectively recruited. The concomitant presence of non-cardioembolic features (small vessel occlusion [SVO] or large artery atherosclerosis [LAA]) on imaging was evaluated. The frequency of and factors associated with co-existing SVO/LAA features were assessed. Results A total of 560 consecutive patients with AF and acute stroke (237 women; median age 78 [IQR 71–85] years; NIHSS score 9 [3-20]) were enrolled. Of these, 42 (7.5%) had co-existing SVO/LAA features. Multivariable logistic regression analysis showed that the brain natriuretic peptide level (BNP, OR 0.78, p = .030 per 100 pg/mL increase) was independently and negatively associated with co-existing SVO/LAA features and receiver operating characteristic curve analysis revealed the practical cut-off BNP value was 130 pg/mL (sensitivity 54% and specificity 68%). Conclusion SVO/LAA features were found in 7.5% of acute stroke patients with AF. A relatively low BNP level on admission was independently associated with co-existing SVO/LAA features. Thorough examination for a more appropriate etiology may be particularly necessary in acute stroke patients with AF and a relatively low BNP level.