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Background Removal of anti-blood group antibodies is important for successful ABO-incompatible kidney transplantation (ABOi-KTx). Double-filtration plasmapheresis (DFPP) using albumin solution removes antibodies effectively. However, fibrinogen is largely removed resulting in hemostatic failure. Herein, we designed an altered combination of plasma membranes in DFPP (novel DFPP, nDFPP) to retain more fibrinogen while removing IgG, and assessed its efficacy and safety compared with conventional DFPP (cDFPP). Methods Consecutive ABOi-KTx recipients (from 2015 to 2018) were enrolled. For the first membrane, we used Cascadeflo EC-50W in nDFPP and Plasmaflo OP-08W in cDFPP, and Cascadeflo EC-20W as the second membrane in both modalities. Removal rates (RR) of IgG, IgM and fibrinogen per DFPP session, and adverse events were compared with historical control patients who underwent cDFPP before ABOi-KTx, between 2006 and 2015. Results nDFPP and cDFPP groups included 12 and 23 cases, respectively. nDFPP was inferior to cDFPP in RR of IgG and IgM. nDFPP was also inferior to cDFPP in the decline in anti-blood group IgG and IgM antibody titers. However, fibrinogen was more preserved in nDFPP compared with cDFPP, indicating that nDFPP has more selective removal properties (median RR of IgG, IgM, and fibrinogen: 62.1%, 15.7% and 37.6%, respectively, in nDFPP; and 74.5%, 85.0% and 76.6%, respectively, in cDFPP). In the comparison of hemostatic function among the patients who had arteriovenous fistula for hemodialysis, prolonged hemostasis (> 20 min) at the cannulation site was significantly less frequently observed in nDFPP group (1 in 9 cases, 9.1%) than in cDFPP group (all 18 cases, 10%, p < 0.0001). Conclusions nDFPP preserves fibrinogen while removing anti-blood type IgG antibodies before ABOi-KTx.

type:Journal Article, In this paper, we describe the wafer bonding technology Si (100) substrate and GaN/Si (111) substrate using surface activated bonding at room temperature and the removal technique for Si (111) substrate underneath the GaN and buffer layers for 3D power-supply on chip., 9th IEEE CPMT Symposium Japan (ICSJ2019), 18-20 November, 2019, Kyoto University, Kyoto, Japan

BackgroundTransabdominal ultrasonography (US) has been reported to be a useful tool for evaluating ulcerative colitis (UC) although with less well-established data than for Crohn's disease. This prospective multicenter study aimed to establish the usefulness of US compared with colonoscopy (CS) for assessing disease extent and activity of UC.MethodsAltogether, 173 patients with UC were prospectively enrolled, among whom 156 were eligible for this study. All patients underwent US and CS within 2days at five facilities. We divided the colon into six segments and examined each segment and the rectum using US and CS. US severity was graded 1-4 regarding bowel wall thickness, stratification, and ulceration. CS severity was also graded 1-4 according to Matts' endoscopic classification. Concordance between US and CS grades for all colonic segments was analyzed using kappa statistics. US and CS findings were also compared with the clinical disease activity index (CAI) and histological grade using Spearman's correlation coefficient.ResultsThere was moderate concordance between US and CS grades in all colonic segments (weighted =0.55, p<0.001). Concordance was rated moderate for each colonic segment but only slight for the rectum. The US grade was significantly correlated with the CAI score (r=0.40, p<0.001) and histological grade (r=0.35, p<0.001).ConclusionsThis prospective multicenter study showed moderate concordance between US and CS for assessing the disease activity of UC. Hence, US may be used more generally for evaluating UC in daily clinical practice.

Purpose Spinal angiography is the gold standard for evaluation or diagnosis of spinal arteriovenous malformations (AVMs). However, some feeding arteries might be overlooked when multiple feeders exist. This study aimed to retrospectively review cases of spinal intra-dural AVMs, which were identified by three-dimensional digital subtraction angiography (3D-DSA), and attempted to estimate the number of feeding arteries.Methods We retrospectively reviewed patients with spinal intra-dural AVMs who underwent 3D-DSA at Hokkaido University Hospital from January 2005 to December 2016. We selected 9 patients in whom we could obtain data of multi-planar reconstruction of 3D-DSA. We measured the computed tomography (CT) values of feeding arteries and draining veins. The CT values represented the averages of maximum CT values of 5 continuous axial slices. The ratio of the CT value of feeders to that of drainers (F/D ratio) was calculated. The correlation between the F/D ratio and the number of feeders was examined with Pearson's correlation coefficient.Results The average number of feeders was 2.3 (1-4), and the number of feeders was significantly positively correlated with the F/D ratio (r=0.855, P=.003).Conclusions We conclude that the number of feeding arteries of spinal intra-dural AVMs can be estimated by using the F/D ratio obtained from 3D-DSA.

Background Outcomes of endovascular treatment for acute ischemic stroke depend on the time interval from onset to reperfusion. Although the centralized 'mothership' method is considered preferable, the required transportation time increases the risk that a patient with a stroke may not receive intravenous or endovascular therapy. In contrast, 'drive and retrieve' describes a system wherein doctors from comprehensive stroke centers travel to primary stroke centers and provide endovascular treatment for acute ischemic stroke. Objective To describe the drive and retrieve system and verify the effects of this new collaboration on outcomes in patients with acute ischemic stroke among facilities. Methods This non-randomized, single-arm study retrospectively analyzed patients who met the inclusion criteria for endovascular treatment provided through a drive and retrieve system. Among the 122 patients treated by this system, we analyzed the time of onset to recanalization as the primary outcome. We also analyzed the efficacy of the drive and retrieve system using geographic information system analysis. Results The median time from onset to recanalization was 229 min (IQR 170-307 min, 95% CI 201 to 252 min). The upper limit of the 95% CI for the time from onset to recanalization was shorter than the median times reported in two previous trials. Geographic information system analysis revealed an upward trend in the population coverage rate in each secondary medical area after the drive and retrieve method was introduced. Conclusion The drive and retrieve method may be an effective form of cooperation between facilities located within 1 hour of a comprehensive stroke center.

type:Journal Article, In recent years, miniaturization and thinning of the power supply are attracted attentions. In this paper, we discuss the structure for the on-chip inductor and assembly technology suitable for 3D power SoC, which stacks GaN power device, passive devices, control circuit, and driver, based on wafer direct bonding technology and clarified the potential of the high frequency switching applications. We also propose the optimum structure and technology according to the switching frequency based on simulations., 2018 IEEE 68th Electronic Components and Technology Conference (ECTC), 29 May-1 June 2018, San Diego, CA, USA

type:Conference Paper, Recently, power-SoC has been attracting attentions because it can realize ultimate miniaturization of power supply. The silicon-on-insulator (SOI) technology is one of the promising candidates for realizing power-SoC because this technology is suitable for high frequency switching, that is resulting from its smaller parasitic capacitance. However, the conventional SOI structure has a problem of self-heating because of low thermal conductivity of SiO2. In such situations, hexagonal-BN(h-BN) is attractive for the buried insulator layer of SOI because it has higher thermal conductivity with atomically flat surface (Ra of h-BN < 0.25 nm). In this paper, we evaluate the thermal performance of a 3D stacked power SoC utilizing h-BN as an insulator and thermal interface material through numerical simulations. We also discuss the impact of the through-silicon-via (TSV) for heat dissipation., Integrated Power Conversion and Power Management (PwrSoc 2018), October 17-19, 2018, Hsinchu, Taiwan, source:http://pwrsocevents.com

Background Outcomes of endovascular treatment for acute ischemic stroke depend on the time interval from onset to reperfusion. Although the centralized 'mothership' method is considered preferable, the required transportation time increases the risk that a patient with a stroke may not receive intravenous or endovascular therapy. In contrast, 'drive and retrieve' describes a system wherein doctors from comprehensive stroke centers travel to primary stroke centers and provide endovascular treatment for acute ischemic stroke. Objective To describe the drive and retrieve system and verify the effects of this new collaboration on outcomes in patients with acute ischemic stroke among facilities. Methods This non-randomized, single-arm study retrospectively analyzed patients who met the inclusion criteria for endovascular treatment provided through a drive and retrieve system. Among the 122 patients treated by this system, we analyzed the time of onset to recanalization as the primary outcome. We also analyzed the efficacy of the drive and retrieve system using geographic information system analysis. Results The median time from onset to recanalization was 229 min (IQR 170-307 min, 95% CI 201 to 252 min). The upper limit of the 95% CI for the time from onset to recanalization was shorter than the median times reported in two previous trials. Geographic information system analysis revealed an upward trend in the population coverage rate in each secondary medical area after the drive and retrieve method was introduced. Conclusion The drive and retrieve method may be an effective form of cooperation between facilities located within 1 hour of a comprehensive stroke center.

Background: Oxygen uptake (V̇O2) at peak workload and anaerobic threshold (AT) workload are often used for grading heart failure (HF) severity and predicting all-cause mortality. The clinical relevance of respiratory exchange ratio (RER) during exercise, however, is unknown.Methods and Results: We retrospectively studied 295 HF patients (57±15 years, NYHA class I–III) who underwent cardiopulmonary exercise testing. RER was measured at rest; at AT workload; and at peak workload. Peak V̇O2 had an inverse correlation with RER at AT workload (r=−0.256), but not at rest (r=−0.084) or at peak workload (r=0.090). Using median RER at AT workload, we divided the patients into high RER (≥0.97) and low RER (<0.97) groups. Patients with high RER at AT workload were characterized by older age, lower body mass index, anemia, and advanced NYHA class. After propensity score matching, peak V̇O2 tended to be lower in the high-RER than in the low-RER group (14.9±4.5 vs. 16.1±5.0 mL/kg/min, P=0.06). On Kaplan-Meier analysis, HF patients with a high RER at AT workload had significantly worse clinical outcomes, including all-cause mortality and rate of readmission due to HF worsening over 3 years (29% vs. 15%, P=0.01). Conclusions: High RER during submaximal exercise, particularly at AT workload, is associated with poor clinical outcome in HF patients.

Introduction: Fatty acid oxidation disorders (FAODs) are rare diseases caused by defects in mitochondrial fatty acid oxidation (FAO) enzymes. While the efficacy of bezafibrate, a peroxisome proliferator-activated receptor agonist, on the in vitro FAO capacity has been reported, the in vivo efficacy remains controversial. Therefore, we conducted a clinical trial of bezafibrate in Japanese patients with FAODs. Materials and methods: This trial was an open-label, non-randomized, and multicenter study of bezafibrate treatment in 6 patients with very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency and 2 patients with carnitine palmitoyltransferase-II (CPT-2) deficiency (median age, 8.2 years; ranging from 5.8 to 26.4 years). Bezafibrate was administered for 6 months following a 6-month observation period. The primary endpoint was the frequency of myopathic attacks, and the secondary endpoints were serum acylcarnitines (ACs, C14:1 or C16 + C18:1), creatine kinase (CK) levels, degree of muscle pain (VAS; visual analog scale) during myopathic attacks, and quality of life (QOL; evaluated using validated questionnaires). Results: The frequency of myopathic attacks after bezafibrate administration decreased in 3 patients, increased in 3, and did not change in 2. The CK, AC, and VAS values during attacks could be estimated in only three or four patients, but a half of the patients did not experience attacks before or after treatment. Changes in CK, AC, and VAS values varied across individuals. In contrast, three components of QOL, namely, physical functioning, role limitation due to physical problems (role physical), and social functioning, were significantly elevated. No adverse drug reactions were observed. Conclusion: In this study, the frequency of myopathic attacks and CK, AC, and VAS values during the attacks could not be evaluated due to several limitations, such as a small trial population. Our findings indicate that bezafibrate improves the QOL of patients with FA

We compared treatment satisfaction between daily dipeptidyl peptidase-4 (DPP-4) inhibitors and a weekly DPP-4 inhibitor in patients with type 2 diabetes. The study was a 12-week, open-label, randomized, multicenter, controlled trial. Participants were Japanese patients with type 2 diabetes who had received daily DPP-4 inhibitors for more than 3 months. Patients were randomly assigned to a treatment cohort: (1) a group that continued taking daily DPP-4 inhibitors (daily group); or (2) a group that switched from daily DPP-4 inhibitors to a weekly DPP-4 inhibitor, trelagliptin (weekly group). The primary outcome was the change in treatment satisfaction levels from baseline to 12 weeks between the two groups, according to Diabetes Treatment Satisfaction Questionnaire (DTSQ) and Diabetes Therapy-Related Quality of Life (DTR-QOL) questionnaire scores. The changes in glycemic control and body weight were also assessed. Of 49 patients initially enrolled in the study, 47 completed the study. The change in DTSQ scores in the weekly group was not significantly different from that in the daily group. However, the improvements in total score and subscale domains 1 and 2 in the DTR-QOL analysis, which relate to burden on social/daily activities and anxiety/dissatisfaction with treatment, were significantly greater in the weekly group than the daily group (p = 0.048, 0.013 and 0.045, respectively). Mean changes in glycated hemoglobin levels and body weight were comparable between the groups. Switching from daily DPP-4 inhibitors to a weekly DPP-4 inhibitor, trelagliptin, could partially improve treatment satisfaction levels in patients with type 2 diabetes without affecting glycemic control.

This is a report of a single-institution prospective study evaluating the safety of a spot-scanning dedicated, small 360-degree gantry, synchrotron-based proton beam therapy (PBT) system. Data collection was performed for 56 patients with 59 treatment sites who received proton beam therapy at Hokkaido University Hospital between March 2014 and July 2015. Forty-one patients were male and 15 were female. The median age was 66 years. The primary lesion sites were prostate (n = 17), bone/soft tissue (n = 10), liver (n = 7), lung (n = 6), central nervous system (n = 5), colon (n = 2), pancreas (n = 2), kidney (n = 2) and others (n = 5). Chemotherapy was administered in 11 patients. The prescribed total dose was from 20 to 76 GyE (Radiobiological equivalent dose, RBE = 1.1), with the median dose of 65 GyE in 4 to 35 fractions. No PBT-related Common Terminology Criteria for Adverse Events Grade 4 or 5 toxicities were observed; the incidence of early PBT-related Grade 4 adverse events was 0% (95% confidence interval 0 to 6.38%). The most common Grade 3 toxicities were hematologic toxicity (12.5%) unlikely to be related to the PBT. One patient developed a left femoral neck fracture (Grade 3) at 14.5 months after PBT for chondrosarcoma of the left pelvis. The pathological findings showed no other malignancies, suggesting that it was possibly related to the PBT. In conclusion, the spot-scanning dedicated, synchrotron-based PBT system is feasible, but further studies on its long-term safety and efficacy are warranted.

Background: Metachronous multiple squamous cell carcinoma (SCC) of the esophagus and the head and neck is commonly observed in patients who have previously undergone endoscopic resection (ER) for SCC of the esophagus (ESCC). We evaluated the risk for developing metachronous SCC following ER for ESCC based on the genetic polymorphisms for alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) as well as the alcohol consumption and smoking habits. Methods: We studied 158 patients who underwent ER for ESCC (median follow-up 80 months). Genotyping of ADH1B/ALDH2 was performed using saliva sampling. The alcohol consumption and smoking histories of the patients before and after the ER were documented. Results: Multivariate analyses revealed that inactive heterozygous ALDH2 [hazard ratio (HR) 2.25] and alcohol consumption after ER (HR 1.94) were independently associated with the risk of developing secondary SCC. Moreover, inactive heterozygous ALDH2 (HR 4.39) and alcohol consumption after the ER (HR 2.82) were independently associated with the risk of a third SCC. We analyzed 110 patients who had a history of moderate or heavy alcohol consumption before the ER. The 3-year cumulative incidence rates of secondary SCC in the temperance (n = 65) and non-temperance groups (n = 45) were 14.0 and 42.1% (p = 0.0002). Further, the 5-year cumulative incidence rates of a third SCC in the temperance and non-temperance groups were 0 and 15.6% (p = 0.0011), respectively. In addition, the 7-year cumulative incidence rates of a fourth SCC in the temperance and non-temperance groups were 0 and 15.3% (p = 0.0015), respectively. Conclusions: Continued alcohol consumption is an important risk factor for the onset of metachronous SCC and is a risk factor for the third and subsequent SCCs. Strict advice in favor of temperance is crucial.

OBJECTIVE: In combined revascularization surgery for patients with moyamoya disease, intracerebral hemorrhage (ICH) during the postoperative acute phase is a rarely observed but severe complication. Its clinical features remain unclear because of its low incidence rate. The aim of this study was to clarify the clinical characteristics of immediate postoperative ICH. METHODS: The frequency, onset timing, and hematoma location of patients who demonstrated immediate postoperative ICH were investigated in 201 consecutive surgeries performed in 134 patients. Associations between immediate postoperative ICH and demographics, clinical presentation type, perioperative blood pressure (BP), and neuroimaging data were analyzed. RESULTS: Postoperative ICH was observed in 6 cases (2.99%; mean age, 46.0 +/- 1 7.6 years). The onset timing of ICH was within 24 hours after surgery in most patients (83.3%). Hematomas were located at the subcortical lesion beneath the anastomosed cortex (n = 5) and caudate head (n = 1). Three cases (50.0%) required hematoma evacuation. A higher age at surgery was associated with postoperative ICH (P = 0.046). In adult cases (132 surgeries, 65.7%), hemorrhagic presentation at onset (P = 0.0027) and an increase in BP from pre- to postoperative stage (systolic BP increase: P = 0.0058, diastolic BP increase: P = 0.0274) were significantly associated with postoperative ICH. CONCLUSIONS: The results suggest that older patients, with hemorrhagic presentation and greater postoperative BP increase, should be carefully managed to avoid postoperative ICH. Immediate hematoma evacuation may be effective in preventing devastating outcomes after postoperative ICH.

This is a report of a single-institution prospective study evaluating the safety of a spot-scanning dedicated, small 360-degree gantry, synchrotron-based proton beam therapy (PBT) system. Data collection was performed for 56 patients with 59 treatment sites who received proton beam therapy at Hokkaido University Hospital between March 2014 and July 2015. Forty-one patients were male and 15 were female. The median age was 66 years. The primary lesion sites were prostate (n = 17), bone/soft tissue (n = 10), liver (n = 7), lung (n = 6), central nervous system (n = 5), colon (n = 2), pancreas (n = 2), kidney (n = 2) and others (n = 5). Chemotherapy was administered in 11 patients. The prescribed total dose was from 20 to 76 GyE (Radiobiological equivalent dose, RBE = 1.1), with the median dose of 65 GyE in 4 to 35 fractions. No PBT-related Common Terminology Criteria for Adverse Events Grade 4 or 5 toxicities were observed; the incidence of early PBT-related Grade 4 adverse events was 0% (95% confidence interval 0 to 6.38%). The most common Grade 3 toxicities were hematologic toxicity (12.5%) unlikely to be related to the PBT. One patient developed a left femoral neck fracture (Grade 3) at 14.5 months after PBT for chondrosarcoma of the left pelvis. The pathological findings showed no other malignancies, suggesting that it was possibly related to the PBT. In conclusion, the spot-scanning dedicated, synchrotron-based PBT system is feasible, but further studies on its long-term safety and efficacy are warranted.