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Acute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Stem cell source or HLA disparity may exert a significant impact on the overall survival (OS) after the development of aGVHD. In order to clarify this point, we performed a retrospective analysis using a database of the Japan Society for HCT. We analyzed the clinical outcomes of 10,035 patients who developed grade II-IV aGVHD. The median age of the patients was 48 years. The probability of 2-year OS after the onset of grade II-IV aGVHD in the study cohort was 54.1%. The multivariate analysis showed that the HLA ≥2-loci mismatched related donor and HLA 1-locus mismatched unrelated donor were significantly associated with an inferior OS after grade II-IV aGVHD. In a subgroup analysis, peripheral blood stem cells and HLA disparity were associated with an inferior OS in patients who received related or unrelated HCT. Thus, the clinical outcome after grade II-IV aGVHD significantly varied as per the combination of the presence of HLA disparity and stem cell source. Further research using other databases is necessary to confirm our findings.

Introduction: In patients requiring both hemodialysis (HD) and apheresis, the 2 treatments can be performed simultaneously. At our hospital, selective plasma exchange (SePE) is often performed along with HD for removal of isoagglutinins before ABO-incompatible (ABOi) kidney transplantation. The 2 treatments can be completed within the HD schedule, which allows the treatment time to be shortened. This approach is also less stressful for patients because fewer punctures are required. In this study, we investigated the safety and efficacy of tandem HD and SePE. Methods: A total of 58 SePE sessions in 30 ABOi kidney transplant recipients were investigated. The SePE circuit was connected in parallel with the HD circuit, and tandem HD and SePE therapy was performed using filtration methods. The SePE sessions were divided into 2 groups: those with SePE monotherapy (group S, n = 20) and those with tandem therapy (group T, n = 38). Changes in transmembrane pressure (TMP), arterial pressure (AP), venous pressure (VP), and decrease in isoagglutinin titers over time were compared between the groups with adjustment for background data. Results: The internal pressures (AP and VP) were higher in group T, and there were significant differences in changes of TMP and AP over time between groups T and S. Membrane exchange was required in 1 case in group T due to coagulation. There was a more significant decrease of immunoglobulin G isoagglutinin titers in group T compared to group S. No case had antibody-mediated rejection after transplantation. Discussion/Conclusion: In HD/SePE tandem therapy, internal pressures were higher and TMP and AP tended to increase more compared to SePE monotherapy, but we were able to perform the 2 treatments without any functional problems. Tandem therapy was also effective in decreasing isoagglutinin titers, which suggests that this may be a beneficial treatment modality as apheresis before ABOi kidney transplantation.

The use of antiplatelet drugs is thought to increase the risk for intracerebral hemorrhage (ICH) in patients with cerebral microbleeds (CMBs). However, hemodialysis (HD) patients have a high prevalence of CMBs and diverse pathologies that require antiplatelet therapy. In this study, we investigated whether the use of antiplatelet drugs increases the risk for ICH in HD patients with CMBs. Brain magnetic resonance imaging (MRI), including T2*-weighted MRI, was performed in 179 HD patients with no history of cerebrovascular events. CMBs were detected and patients were followed prospectively with a median follow-up period of 5.2 [1.4-6.2] years. To investigate whether the influence of antiplatelet therapy on the development of ICH differs in cases with and without CMBs, the inverse probability of treatment weighting method was used, including an interaction term between the presence or absence of CMBs and use of antiplatelet drugs. As a result, CMBs were detected in 45 patients (25.1%), and antiplatelet drugs were used in 66 patients (36.9%). When the effect of antiplatelet therapy on the incidence of ICH was modified by the presence of CMBs at baseline (P for interaction0.001), the use of antiplatelet drugs was a significant risk factor for ICH in HD patients without CMBs, but not in HD patients with CMBs. Furthermore, the burden of CMBs significantly increased the risk for ICH, but the increase in this risk was slower in antiplatelet drug users as compared to non-antiplatelet drug users (P for interaction = 0.02). The influence of antiplatelet drugs on the development of ICH differed depending on the presence or absence of CMBs. In fact, the use of antiplatelet drugs did not increase the risk for ICH in HD patients with CMBs.

The ability of perioperative fluid management to prevent postoperative recurrence of atrial tachyarrhythmia remains controversial. The aim of the present study was to assess if intraoperative net fluid balance was associated with atrial tachyarrhythmia recurrence after the Cryo-Maze procedure.An observational cohort study.A tertiary care hospital from April 2007 to May 2019.Four hundred forty-four patients undergoing the Cryo-Maze procedure in conjunction with other cardiac surgeries.The Cryo-Maze procedure in conjunction with other cardiac surgeries.The main outcome was early atrial tachyarrhythmia recurrence, consisting of atrial fibrillation, atrial flutter, or atrial tachycardia, within the first three months after surgery. Complete follow-up was achieved in 443 patients (99.8%), of them 127 (28.6%) developed early atrial tachyarrhythmia recurrence. The median intraoperative net fluid balance was 1,627 mL (interquartile range, -215 to 3,557 mL). Multivariate logistic regression showed that intraoperative net fluid balance (p = 0.001), preoperative AF duration (adjusted odds ratio, 1.40; 95% CI, 1.17-1.68; p0.001) and left atrial volume index (aOR, 1.61; 95% CI, 1.06-2.45; p = 0.025) were independent predictors of early atrial tachyarrhythmia recurrence. The adjusted log odds were lowest (-1.52) when net fluid balance was 1,557 mL.There is a significant U-shaped association between intraoperative net fluid balance and early atrial tachyarrhythmia recurrence among patients undergoing the Cryo-Maze procedure.

Introduction: Chronic low back pain (CLBP) is a leading cause of disability, yet there is limited high-quality evidence to identify the most suitable pharmacological therapy. The purpose of this Japanese nationwide, multicenter, prospective study was to compare the effectiveness of four representative drug therapies―acetaminophen, celecoxib, loxoprofen, and a tramadol and acetaminophen (T+A) combination drug―to establish evidence for a drug of choice for CLBP. Methods: Patients with CLBP (N=471) received one of the four treatments and were evaluated, prospectively and comprehensively, once every month for six months using a visual analog scale (VAS) for LBP, the Japanese Orthopedic Association (JOA) score, the JOA Back Pain Evaluation Questionnaire (JOABPEQ), the Roland-Morris Disability Questionnaire (RDQ), the EuroQol five-dimensions three-levels (EQ-5D-3L), and the Short Form-8 item health survey (SF-8). We conducted multivariable linear regression analyses of the four drugs at 1 and 6 months after drug allocation. Differences with P

Background The gut microbiota are reported to be altered in critical illness. The pattern and impact of dysbiosis on prognosis has not been thoroughly investigated in the ICU setting. Aims We aimed to evaluate changes in the gut microbiota of ICU patients via 16S rRNA gene deep sequencing, assess the association of the changes with antibiotics use or disease severity, and explore the association of gut microbiota changes with ICU patient prognosis. Methods Seventy-one mechanically ventilated patients were included. Fecal samples were collected serially on days 1–2, 3–4, 5–7, 8–14, and thereafter when suitable. Microorganisms of the fecal samples were profiled by 16S rRNA gene deep sequencing. Results Proportions of the five major phyla in the feces were diverse in each patient at admission. Those of Bacteroidetes and Firmicutes especially converged and stabilized within the first week from admission with a reduction in α-diversity (p 8 or

Background To evaluate the effectiveness of the nurse-led alcohol guidance to control home blood pressure (HBP) in the morning among male patients with hypertension during outpatient visits. Methods We enrolled 53 male patients with an HBP of ≥135/85 mm Hg with excessive drinking (alcohol ≥210 g/week or ≥60 g/day habitually) among outpatients in a randomized trial. Patients were assigned to a nurse-led alcohol guidance intervention or to the control. The primary outcomes were the mean HBP of 5 consecutive days at 6 months and alcohol consumption. Results Twenty-eight and 25 patients were randomized to intervention and control groups, respectively (mean age; 62.7 years old and 64.5, respectively). At baseline, the groups were well balanced across most characteristics. At 6 months, the mean HBP was 131/82 mm Hg in the intervention group vs. 145/87 mm Hg in the control group (SBP Conclusions We confirmed the effectiveness of the nurse-led alcohol guidance to control the HBP in male patients with hypertension during outpatient visits. Public trials registry number UMIN000017454 (UMIN Clinical Trials Registry).

We investigated the relationship between trunk muscle mass and spinal pathologies by gender. This multicenter cross-sectional study included patients aged ≥ 30 years who visited a spinal outpatient clinic. Trunk and appendicular muscle mass were measured using bioelectrical impedance analysis. The Oswestry Disability Index (ODI), visual analog scale (VAS) score for low back pain, sagittal vertical axis (SVA), and EuroQol 5 Dimension (EQ5D) score were investigated to evaluate spinal pathology. The association between trunk muscle mass and these parameters was analyzed by gender using a non-linear regression model adjusted for patients’ demographics. We investigated the association between age and trunk muscle mass. We included 781 men and 957 women. Trunk muscle mass differed significantly between men and women, although it decreased with age after age 70 in both genders. Lower trunk muscle mass was significantly associated with ODI, SVA, and EQ5D score deterioration in both genders; its association with VAS was significant only in men. Most parameters deteriorated when trunk muscle mass was

BACKGROUND AND OBJECTIVES: Vitamin D receptor activators and calcimimetics (calcium-sensing receptor agonists) are two major options for medical treatment of secondary hyperparathyroidism. A higher serum calcification propensity (a shorter T(50) value) is a novel surrogate marker of calcification stress and mortality in patients with CKD. We tested a hypothesis that a calcimimetic agent etelcalcetide is more effective in increasing T(50) value than a vitamin D receptor activator maxacalcitol. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A randomized, multicenter, open-label, blinded end point trial with active control was conducted in patients with secondary hyperparathyroidism undergoing hemodialysis in Japan. Patients were randomly assigned to receive intravenous etelcalcetide 5 mg thrice weekly (etelcalcetide group) or intravenous maxacalcitol 5 or 10 µg thrice weekly (maxacalcitol group). The primary, secondary, and tertiary outcomes were changes in T(50) value, handgrip strength, and score of the Dementia Assessment Sheet for Community-Based Integrated Care System from baseline to 12 months, respectively. RESULTS: In total, 425 patients from 23 dialysis centers were screened for eligibility, 326 patients were randomized (etelcalcetide, n=167; control, n=159), and 321 were included in the intention-to-treat analysis (median age, 66 years; 113 women [35%]). The median (interquartile range) of T(50) value was changed from 116 minutes (interquartile range, 90–151) to 131 minutes (interquartile range, 102–176) in the maxacalcitol group, whereas it was changed from 123 minutes (interquartile range, 98–174) to 166 minutes (interquartile range, 127–218) in the etelcalcetide group. The increase in T(50) value was significantly greater in the etelcalcetide group (difference in change, 20 minutes; 95% confidence interval, 7 to 34 minutes; P=0.004). No significant between-group difference was found in the change in handgrip strength or in the Dementia Assessment Sheet for Community-Based Integrated Care System score. CONCLUSIONS: Etelcalcetide was more effective in increasing T(50) value than maxacalcitol among patients on hemodialysis with secondary hyperparathyroidism. There was no difference in handgrip strength or cognition between the two drugs. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: VICTORY; UMIN000030636 and jRCTs051180156

Aim Both oxidative stress and inflammation are involved in the pathogenesis of cardiovascular disease (CVD). The serum level of derivatives of reactive oxygen metabolites (d-ROMs) is a measure of the total amount of hydroperoxides serving as a marker of oxidative stress. We investigated whether d-ROMs could predict the clinical outcomes in hemodialysis patients and whether the associations of d-ROMs with the outcomes are independent of a marker of inflammation, C-reactive protein (CRP). Methods This was a prospective cohort study in hemodialysis patients. The key exposures were the serum levels of d-ROMs and CRP. The outcome measures were all-cause mortality and new CVD events. Results A total of 517 patients were analyzed. d-ROMs correlated positively with CRP. During follow-up for 5 years, 107 patients died, and 190 patients experienced new CVD events. In the Kaplan-Meier analyses, both higher d-ROMs and higher CRP levels predicted higher risks for mortality and CVD events. By Cox proportional-hazard regression analysis adjusted for potential confounders excluding CRP, d-ROMs exhibited a significant association with all-cause mortality, but this association was no longer significant after further adjustment for CRP. Using the same model, CRP exhibited a significant association with all-cause mortality, but this association was no longer significant after further adjustment for d-ROMs. When we analyzed new CVD events as the outcome, CRP was a significant predictor, whereas the level of d-ROMs was not. Conclusions Although d-ROMs predicted mortality and CVD events in unadjusted models, the associations of d-ROMs with these outcomes were not independent of CRP. Oxidative stress and inflammation appear to share common causal pathways.

Aim Although nivolumab improves progression-free (PFS) and overall (OS) survival of patients previously treated for metastatic non-small-cell lung cancer (NSCLC), approximately 50% of treated patients experience disease progression within 3 months. As predictive biomarkers of response are not yet established, development of biomarkers to predict longer PFS and OS of patients treated with nivolumab is crucial. Therefore, we analyzed the impact of predictive markers of response to nivolumab and quantified the impact of each factor using nomograms. Patients and methods Clinical data at nivolumab commencement were retrospectively collected from 201 patients treated with nivolumab between December 2015 and July 2016. Immunohistochemistry for programmed cell death ligand 1 (PD-L1) was performed using two assay systems (22C3 and 28-8). OS was calculated from nivolumab treatment initiation. Multivariate Cox regression analysis was conducted to identify independent predictors of OS. A nomogram was constructed to estimate OS. Results The median patient age was 68 years (135 males). Thirty-nine patients had driver mutations (epidermal growth factor receptor mutations and anaplastic lymphoma kinase rearrangement). In 22C3 and 28-8 immunostaining assays, 36.3% and 36.8% patients had PD-L1-negative cells, 17.4% and 14.4% had 1-49% PD-L1-positive cells, 11.9% and 14.9% had ≥50% PD-L1-positive cells, and 34.3% and 33.8% had unknown PD-L1 status, respectively. Kendall's rank correlation coefficient between the staining assays was 0.8414. The median OS of the whole patient cohort was 12.27 months [95% confidence interval (CI)=10.87-15.6]. Performance status ≥2 [hazard ratio (HR)=2.15, 95% CI=1.35-3.42, p=0.001) and high baseline lactate dehydrogenase (HR=1.15, 95% CI=1.05-1.26, p=0.004] were independent predictors of shorter OS. There was no significant correlation between PD-L1 status and OS. We constructed a nomogram to estimate the OS of patients previously treated with nivolumab. Conclusion The multivariate analysis-based nomogram might be useful to estimate the OS of patients previously treated with nivolumab for advanced NSCLC.

Introduction: Chronic low back pain (CLBP) is a major health burden worldwide and requires patient satisfaction with treatment. Consultation length can be an important factor in patient satisfaction, but few studies have investigated the impact of consultation length on satisfaction in patients with CLBP. This study tried to elucidate the impact of consultation length on clinical outcomes in patients with CLBP. Methods: This study is part of an analysis using the database of the nationwide, multicenter cohort for CLBP performed by the Project Committee of the Japanese Society for Spine Surgery and Related Research. A total of 427 patients aged 20-85 years (median age, 73.0 years; female, 58.6%) with CLBP were prospectively followed-up monthly for 6 months. Multivariable nonlinear regression analyses were performed to assess the effect of consultation length on outcome measures including subjective satisfaction score, EuroQol 5-dimension, Japanese Orthopaedic Association (JOA) score, Roland-Morris Disability Questionnaire, JOA Back Pain Evaluation Questionnaire, visual analog scale (VAS) and Medical Outcome Survey short-form 8-item health survey that evaluated at the next phase. Furthermore, we assessed whether the effect of consultation length on patient satisfaction was modified by the baseline Brief Scale for Psychiatric Problems in Orthopaedic Patients (BS-POP) score for patient and physician versions. Results: VAS for CLBP was the only score that correlated significantly with consultation length (P = 0.018). Satisfaction score showed a significant positive correlation with consultation length in patients with the highest baseline BS-POP scores (P < 0.2). Moreover, consultation lengths more than 7.6 min and 15.1 min offered increase of satisfaction if patients show the highest BS-POP scores on patient and physician versions, respectively. Conclusions: These findings suggest that a sufficiently long consultation is an important factor for subjective satisfaction in the patients with CLBP, particularly in patients with psychological problems.

We evaluated the influence of anesthetic management with sevoflurane or propofol on recurrence in patients undergoing breast cancer surgery. This single center, retrospective study, included patients who received either sevoflurane or propofol during primary breast cancer surgery between 2008 and 2012. Our primary outcome was recurrence-free survival (RFS) at 1 year. Recurrence was defined as locoregional recurrence and distal metastasis. Propensity scores were calculated using seven variables (age, sex, body mass index, cancer stage, tumor size, intrinsic subtype, and deviation from standard therapy), and Kaplan–Meier survival curves were constructed from the date of diagnosis of recurrence. Hazard ratios (HRs) were estimated using univariable Cox proportional hazard regression analysis. Two-hundred-twelve patients received sevoflurane and 814 patients received total intravenous anesthesia with propofol. The median follow-up was 59 (interquartile range, 44–75) months. Regional anesthetic techniques were not used. Recurrence occurred in 95 patients (9.26%), with 19 (8.96%) and 76 (9.33%) in the sevoflurane and propofol groups, respectively. The HR was 1.167 (95% confidence interval, 0.681–2.000, p = 0.574) for the use of sevoflurane over propofol. After 1:1 propensity-score matching, 318 patients were analyzed. The 1-year RFS rates were similar between the groups (sevoflurane group: 7.5% [n = 12], propofol group: 8.2% [n = 13]), yielding an HR of 1.002 (95% confidence interval 0.457–2.198, p = 0.995) associated with the use of sevoflurane over propofol. In patients undergoing primary breast cancer surgery, the use of either sevoflurane or propofol without regional anesthesia did not appear to affect the risk of recurrence after 1 year.

Background/aimsTo investigate the chronological corneal changes associated with long-term rigid gas-permeable contact lens (RGP-CL) wear in patients with keratoconus (KC).MethodsClinical records of 405 patients with KC or with KC suspect were retrospectively reviewed. Patients with mild-to-moderate KC and uneventful follow-up were classified into the CL (RGP-CL wear) and non-CL (without CL wear) groups. Inclusion criteria were (1) at least 3-year follow-up and (2) Scheimpflug-based corneal imaging examination at each visit. The anterior (ARC) and posterior (PRC) radius of curvature obtained in a 3.0 mm optical zone, the thinnest pachymetry reading of the corneal thickness (Tmin), and maximum keratometry values (Kmax) were investigated as tomographic parameters.ResultsTwenty-two and 15 patients who met the inclusion criteria were included in the CL and non-CL groups, respectively (31 and 20 eyes, respectively). The mean observation periods were 75 (CL group) and 63 (non-CL group) months. A multivariable non-linear regression analysis to assess the change in tomographic parameters over the follow-up period and difference of the trend between the two groups demonstrated no significant differences in the chronological change in ARC, PRC and Tmin between the CL and non-CL groups (p=0.318, p=0.280 and p=0.874, respectively).ConclusionBased on corneal tomographic evaluation over 5–6 years, the effects of long-term RGP-CL wear had no effect on KC progression.

Background It is uncertain whether health counselling after community-based health checkups for high-risk individuals of lifestyle-related disease enhances their referral to physicians. Methods We performed a clustered randomized controlled trial of untreated high-risk individuals aged 40 to 74 years who were screened from the annual health checkup in 2014 and 2015 under the national health insurance in 43 municipalities around Japan, assigning 21 intervention and 22 usual care municipalities. The high-risk conditions were severe forms of hypertension, diabetes, dyslipidemia (for men), and proteinuria. For the intervention group, the theory-based health counselling was performed to enhance referrals to physicians, while each municipality performed its own standard counselling for the usual care group. Data on clinical visits and risk factors were collected systematically and anonymously from the databases of health insurance qualification, health insurance claims, and annual health checkups. Hypotheses are that the cumulative proportion of seeing physicians (clinical visits) is higher in the intervention than the usual care groups, and that those in the intervention group have lower cumulative incidence of composite outcomes associated with lifestyle-related diseases. Results The numbers of subjects for the analyses were 8,977 in the intervention group and 6,733 in the usual care group. Among them, 6,758 had hypertension, 2,147 had diabetes, 2,861 had dyslipidemia, and 1,221 had proteinuria in the intervention group, with corresponding numbers of 4,833, 1,517, 2,262, and 845, respectively, in the usual care group. There were no material differences in mean levels and proportions of major cardiovascular risk factors between the two groups. Conclusions We expect to provide scientific evidence on the effectiveness of health counselling.

Objectives High transprosthetic valvular peak velocity (PV) is indicative of prosthesis–patient mismatch (PPM), which exacerbates mortality and morbidity after surgical aortic valve replacement (AVR). During surgical AVR, a high intraoperative PV sometimes is detected, but whether it affects mortality and morbidity is unknown. The aims of this study were to determine whether intraoperative and postoperative PV were correlated and what factors predicted postoperative PPM. Design Retrospective, observational, cohort study. Setting Tertiary medical center. Interventions None. Measurements and Main Results The study comprised 556 patients who underwent AVR with a bioprosthetic valve. PV was measured intraoperatively, 1 month after surgery, and 1 year after surgery. The occurrence of PPM was defined as an effective orifice area index of less than 0.85 cm2/m2. The associations between PV values at the aforementioned 3 time points were analyzed using a multivariable nonlinear regression model. A multivariable logistic regression model was used to identify the predictors of PPM at 1 year. There was no significant association between intraoperative PV and PV at 1 month (p = 0.419) or 1 year (p = 0.115). The implanted valve type (p Conclusions There was no significant association between intraoperative and postoperative PV values. Implanted valve type and size, but not intraoperative PV, predicted postoperative PPM.

Background Severely burned patients often suffer white blood cell and platelet drop following the injury. Though coagulopathy after burn injury have been reported, the association between leukopenia or thrombopenia and mortality is still unrevealed. To determine whether early drastic drops in white blood cells (WBCs) and platelets following injury can be prognostic markers in patients with major burns. Methods This is a retrospective cohort study setting in a single Burn Center in Japan. Data comprising patients’ characteristics and blood cell counts (red blood cells [RBCs], WBCs including neutrophils, monocytes, and lymphocytes, and platelets) over the first 30 days after burn injury were serially collected from patients suffering major burn injury (≥20% TBSA) from January 1, 2006 to December 31, 2015. To determine blood cell counts affecting 60-day mortality, we used multivariable Cox proportional hazard analysis to assess associations between each blood cell count and mortality, adjusting for age and %TBSA as covariates, and evaluated predicted value of the hazard ratio (HR) of death. Results We enrolled 280 patients. Following burn injury, all blood cell counts were high at admission, then decreased. RBCs diminished progressively and plateaued 2 weeks after injury. WBCs decreased suddenly 2 days after injury, then increased and stabilized. Platelets decreased more rapidly than WBCs to their nadir at 3 days, then continually increased. After covariate adjustment, low RBCs from day 1 (HR: 0.566, 95% C.I. 0.423, 0.759) to day 5 (HR: 0.524, 95% C.I. 0.175, 0.576) were predictors of mortality. Neutrophil count was not a risk factor, but day 3 lymphocyte count (HR: 0.131, 95% C.I. 0.026, 0.646) and day 10 monocyte count (HR: 0.044, 95% C.I. 0.005, 0.396) were risk factors. Low platelet counts from day 3 (HR: 0.545, 95% C.I. 0.300, 0.981) to day 30 following injury were always a predictor of mortality. Conclusions Early thrombopenia and lymphopenia were independent risk factors for 60-day mortality, and prolonged thrombopenia and monocytopenia were independent risk factors for mortality. These findings might shed light on mechanisms of immune response following severe burns.

BackgroundThe Japanese Society for Dialysis Therapy (JSDT) published in 2013 inaugural hemodialysis (HD) guidelines. Specific targets include 1.4 for single-pool Kt/V (spKt/V) with a minimum dose of 1.2, minimum dialysis session length of 4 hours, minimum blood flow rate (BFR) of 200 mL/min, fluid removal rate no more than 15 mL/kg/hr, and hemodiafiltration (HDF) therapy for certain identified symptoms. We evaluated the effect of these guidelines on actual practice in the years spanning 2005 – 2018.MethodsAnalyses were carried out to describe trends in the above HD prescription practices from December 2005 to April 2013 (before guideline publication) to August 2018 based on prevalent patient cross-sections from approximately 60 randomly selected HD facilities participating in the Japan Dialysis Outcomes and Practice Patterns Study.ResultsFrom April 2006 to August 2017 continual rises occurred in mean spKt/V (from 1.35 to 1.49), and percent of patients having spKt/V>1.2 (71% to 85%). Mean BFR increased with time from 198.3 mL/min (April 2006) to 218.4 mL/min (August 2017) , along with percent of patients with BFR >200 ml/min (65% to 85%). HDF use increased slightly from 6% (April 2006 and August 2009) to 8% by April 2013, but increased greatly thereafter to 23% by August 2017. In contrast, mean HD treatment time showed little change from 2006-2017, whereas mean UFR declined from 11.3 in 2006 to 8.4 mL/Kg/hour in 2017.ConclusionsFrom 2006 – 2018 Japanese HD patients experienced marked improvement in reaching the spKt/V target specified by the 2013 JSDT guidelines. This may have been due to moderate increase in mean BFR even though mean HD session length did not change much. In addition, HDF use increased dramatically in this time period. Other HD delivery changes during this time, such as increased use of super high flux dialyzers, also merit study. While we cannot definitively conclude a causal relationship between the publication of the guidelines and the subsequent practice changes in Japan, those changes moved practice closer to the recommendations of the guidelines.

Background: The COVID-19 pandemic has renewed interest and discussion about clinical phenotypes of acute respiratory distress syndrome (ARDS). Since the Berlin definition, various clinical disease courses with fatal outcome have been described but early objective indicators predicting distinct clinical courses have remained elusive. Objectives: Identify clinically available predictors that distinguish between two phenotypes of fatal ARDS due to pneumonia.Methods: 104 Japanese patients with pneumonia induced ARDS were extracted from our prospectively collected database. Fatal cases were divided into early (< 7 days after diagnosis) and late death (≥ 7 days) groups and their clinical variables and prognostic factors were statistically evaluated.Results: Of 50 cases, fatal within 180 days, 18 (36%) comprised the early death group (median 2 days, IQR [1, 5]) and 32 (64%), the late death group (median 16 days, IQR [13, 29]). Multivariate regression analyses showed APACHE II score (HR 1.14, 95%CI 1.01-1.28, p 0.047) was the only independent prognostic factor for early death. Late deaths were associated with disseminated intravascular coagulation score (HR 1.30, 95%CI 1.07-1.58, p 0.007), culture sensitivity to initial antimicrobials (HR 3.42, 95%CI 1.86-6.29, p

Introduction Cerebral microbleeds (CMBs) are detected on gradient-echo T2*-weighted magnetic resonance imaging (MRI). Clinically, CMBs are often detected after stroke, including in cases of intracerebral hemorrhage and ischemic cerebrovascular disease. Hemodialysis (HD) patients are widely known to have a high incidence of stroke, and HD patients without stroke history have been reported to have a high prevalence of CMBs. In this study, we investigated whether history of stroke affects the prevalence of CMBs in HD patients. Methods A cross-sectional study was performed in 241 HD patients who underwent brain T2*-weighted MRI. We compared the prevalence of CMBs between the patients with and without a history of stroke. Moreover, the relationship between history of stroke and presence of CMBs was examined by multivariate logistic regression analysis. Results Among these patients, 22 (9.1%) had a history of stroke. CMBs were detected in 70 patients (29.0%). The prevalence of CMBs was significantly higher in patients with a history of stroke compared to those without this history (54.5 vs. 26.5%, p = 0.012). In the multivariable analysis adjusted for background characteristics, history of stroke was a significant and independent factor related to CMBs (OR: 3.24, 95%CI: 1.18–8.89, p = 0.02). Discussion/conclusions As has been reported for non-dialysis patients, our results showed a high prevalence of CMBs in HD patients with a history of stroke, and indicated that a history of stroke is significantly and independently associated with CMBs in HD patients.

We describe the results of testing healthcare workers from a tertiary care hospital in Japan, which had experienced a COVID-19 outbreak during the first peak of the pandemic, for SARS-CoV-2 specific antibody seroconversion. Using two chemiluminescent immunoassays and a confirmatory surrogate virus neutralization test, serological testing unveiled that a surprising 42.2% (27/64) of overlooked COVID-19 diagnoses had occurred when case detection had relied solely on SARS-CoV-2 nucleic acid amplification testing. This undetected portion of the COVID-19 iceberg beneath the surface may potentially have led to silent transmissions and triggered the spread. A questionnaire-based risk assessment was further indicative of exposures to specific aerosol-generating procedures, i.e. non-invasive ventilation, having had conveyed the highest transmission risks and served as the origin of outbreak. Our observations are supportive of a multi-tiered testing approach, including the use of serological diagnostics, in order to accomplish exhaustive case detection along the whole COVID-19 spectrum.

BACKGROUND AND AIM Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) remains the most common and serious adverse event associated with ERCP. Risk factors for PEP have been described in various reports. However, risk factors have not been quantified to date. The aim of this study was to investigate the risk factors for PEP by quantification of pancreatic volume using pre-ERCP images. METHODS Overall, 800 patients were recruited from April 2012 to February 2015 for this study. There were 168 patients who satisfied the inclusion criteria. Measurement of pancreatic volume was achieved using the volume analyzer SYNAPSE VINCENT in all cases and was used to evaluate the risk factors for PEP. RESULTS According to the criteria established by the consensus guidelines (Cotton classification), 17 patients (10.1%) were classified as having mild disease, 4 (2.4%) as having moderate disease, and 5 (3.0%) as having severe disease. Multivariate model analysis showed that a large pancreatic volume was a significant risk factor for PEP (odds ratio [OR] 1.10, 95% confidence interval [CI] 1.06-1.13; P

Objective The Risk Assessment Profile (RAP) score is used as a tool of risk prediction in post-traumatic venous thromboembolism (VTE), but this scoring system is complicated to use in clinical settings due to its many variables. The objective of this study was to validate the utility of the RAP model and to develop a simpler risk prediction model for post-traumatic VTE. Methods We conducted an observational study at two emergency and critical care centres in Japan between 2013 and 2016. Consecutive adult trauma patients who survived for 24 h or more after admission to the hospital were enroled. One prediction model (quick RAP model) was created with 6 variables based on clinical utility, experience, and thrombogenic mechanism from 17 variables in the conventional RAP model. We calculated diagnostic performance with 95% confidence interval (95% CI) by exact method. Results We identified and analysed 859 patients. Twenty-six patients (3.0%) had VTE (17 with deep venous thrombosis alone, 2 with pulmonary embolism alone, and 7 with both). In the external validation, the RAP model had a sensitivity of 100% (95% CI, 86.8–100%) and specificity of 37.9% (95% CI, 34.6–41.3%). In contrast, the qRAP model had a sensitivity of 96.2% (95% CI, 80.4–99.9%) and specificity of 56.2% (95% CI, 52.7–59.6%). In the internal validation, receiver-operating characteristic curve analysis showed that the two models had similar area under the curve values that were not significantly different (0.832 and 0.800, respectively; RAP vs qRAP, p = 0.477). Conclusions We developed a practical, modified predictive model for VTE, the qRAP model, which appeared only slightly less accurate than the conventional RAP model and had the advantage of being simpler to use to predict VTE. In our dataset, the conventional RAP model was also evaluated as useful for the prediction of post-traumatic VTE.

Background Anticoagulant therapy has seldom been achieved in randomized trials targeting nonspecific overall sepsis patients. Although the key components to identify the appropriate target in sepsis may be disseminated intravascular coagulation (DIC) and high disease severity, the interaction and relation of these two components for the effectiveness of therapy remain unknown. Objective This article identifies the optimal target of anticoagulant therapy in sepsis. Methods We used a prospective nationwide cohort targeting consecutive adult severe sepsis patients in 59 intensive care units in Japan to assess associations between anticoagulant therapy and in-hospital mortality according to DIC (International Society on Thrombosis and Haemostasis [ISTH] overt and Japanese Association for Acute Medicine DIC scores) and disease severity (Acute Physiology and Chronic Health Evaluation II [APACHE II] and Sequential Organ Failure Assessment scores). Multivariable Cox proportional hazard regression analysis with nonlinear restricted cubic spline including a two-way interaction term (treatment × each score) and three-way interaction term (treatment × ISTH overt DIC score × APACHE II score) was performed. Results The final study cohort comprised 1,178 sepsis patients (371 received anticoagulants and 768 did not). The regression model including the two-way interaction term showed significant interaction between intervention and disease severity as indicated by the ISTH overt DIC score and APACHE II score (p = 0.046 and p = 0.101, respectively). Three-way interaction analysis revealed that risk hazard was suppressed in the anticoagulant group compared with the control group in the most severe subset of both scores. Conclusion Anticoagulant therapy was associated with better outcome according to the deterioration of both DIC and disease severity, suggesting that anticoagulant therapy should be restricted to patients having DIC and high disease severity simultaneously.

Background/objective Reduction of muscle markers, such as creatine phosphokinase (CK), in rheumatic diseases and its association with reduced muscle mass may be of clinical importance in osteoarthritis (OA). Considering the complexity of secondary sarcopenia, clarifying the association between muscle markers and sarcopenia and disentangling the involvement of OA-related conditions are of clinical importance. We investigated the association between serum muscle biomarkers and sarcopenia among patients with OA, considering the presence of pain and inflammation. Methods Overall, 1425 patients with knee and hip OA scheduled for joint replacement surgery were included in a single-center cross-sectional study from Screening for People Suffering Sarcopenia in Orthopedic cohort of Kobe study. Primary outcome was sarcopenia defined by 2 criteria (the Asian Working Group for Sarcopenia and the European Working Group on Sarcopenia in Older People). Pain and inflammation were measured using the numeric rating scale and serum C-reactive protein (CRP) levels, respectively. Associations between the biomarkers (serum CK, aspartate aminotransferase, alanine aminotransferase) and sarcopenia were examined using logistic regression models. Results Sarcopenia by the Asian Working Group for Sarcopenia criteria was present in 4.0% of patients. In adjusted analyses, sarcopenia was negatively associated with higher serum CK levels, but not with serum aspartate aminotransferase or alanine aminotransferase levels independent of pain score and serum CRP. Neither pain score nor serum CRP level was associated with sarcopenia. Similar results were found when the European Working Group on Sarcopenia in Older People criteria were used. Conclusions Serum CK was associated with sarcopenia, suggesting the potential usefulness for sarcopenia detection regardless of pain or inflammation in OA.

Aims/Introduction To assess the prevalence of diabetic polyneuropathy (DPN)‐related sensory symptoms/signs and associated factors in patients with polyneuropathy, considering non‐linear effects for numerical variables. Materials and Methods A cross‐sectional survey of patients with type 2 diabetes mellitus from 17 primary care clinics across Japan was carried out. DPN and DPN‐related sensory symptoms/signs were diagnosed according to the Diabetic Neuropathy Study Group in Japan criteria. Results Of the 9,914 patients with type 2 diabetes mellitus in this study, 2,745 had DPN and 1,689 had DPN‐related sensory symptoms/signs (61.5% of patients with DPN). There were significant correlations between DPN‐related sensory symptoms/signs and smoking status (odds ratio 2.04 for current and 1.64 for former; P, This manuscript presents the results of a cross‐sectional Japanese study that assessed the risk factors associated with diabetic peripheral neuropathy‐related symptoms among patients with type 2 diabetes and diabetic peripheral neuropathy, with consideration for non‐linear effects for numerical variables. Some of the modifiable risk factors assessed in the large survey database appeared to be associated with diabetic peripheral neuropathy‐related symptoms, namely smoking, alcohol consumption and systolic blood pressure.

Background We examined whether inferior thyroid artery peak systolic velocity (ITA-PSV) predicts an increase in levothyroxine (LT4) dosage in pregnant women with Hashimoto’s thyroiditis. Methods Twenty-two women with Hashimoto’s thyroiditis who were planning and later achieved pregnancy or confirmed as pregnant were enrolled in this retrospective longitudinal observational study. ITA-PSV and thyroid volume were measured using ultrasonography. Serum concentrations of free thyroxine (F-T4), free triiodothyronine (F-T3), and thyroid stimulating hormone (TSH) were simultaneously determined. We adjusted LT4 dosage to maintain serum TSH at

Background Cerebral oximetry (rSO2) may be useful in assessing the probability of return of spontaneous circulation (ROSC). However, the potential of assessing the trend in the rSO2 value has not been discussed when determining the probability of ROSC. Methods This was a retrospective study of out-of-hospital cardiac arrest (OHCA) patients with continuous rSO2 values recorded during cardiopulmonary arrest. We used logistic regression analysis at each time point to investigate the best subsets of rSO2-related variables for ROSC, which included rSO2 (baseline), the baseline value of rSO2; amount of maximum rise, the maximum difference of rSO2 from rSO2 (baseline) over t minutes; ΔrSO2 (t):(amount of maximum rise)/rSO2 (baseline) over t minutes after hospital arrival. Results Among the 90 included patients, 35 achieved ROSC. Area under the curve (AUC) analysis revealed that ΔrSO2 over a 16-min measurement period was significantly higher than ΔrSO2 measured over 4-, 8-, 12-, and 20-min periods. During this 16-min period, the subset showing the best AUC value was interaction of the amount of maximum rise and rSO2 (baseline) rather than the amount of maximum rise or ΔrSO2 alone (AUC = 0.91). Conclusions The combination of rSO2 (baseline) with the amount of maximum rise in rSO2 value over time might be a new index for the prediction of ROSC that could be useful in guiding cardiopulmonary resuscitation. Further studies are needed to validate these findings.

A multicenter cross-sectional study. To clarify the relationship of trunk muscle mass with low back pain, spinal sagittal balance, and quality of life. Few reports have investigated the relationship of trunk muscle mass with lumbar spine function and spinal balance, and the clinical significance of trunk muscle mass remains unclear. Patients attending spinal outpatient clinics at 10 different medical institutions were enrolled in this study. Patient demographics, trunk muscle mass and appendicular skeletal muscle mass (ASM) measured by bioelectrical impedance analysis (BIA), body mass index (BMI), Charlson Comorbidity Index (CCI), the Oswestry Disability Index (ODI), visual analog scale (VAS) for low back pain, sagittal vertical axis (SVA), and EuroQol 5 Dimension (EQ5D) score were investigated. Multivariate nonlinear regression analysis was used to investigate the association of trunk muscle mass with the ODI, VAS score, SVA, and EQ5D score. Of 2551 eligible patients, 1738 (mean age 70.2 ± 11.0 years; 781 men and 957 women) were enrolled. Trunk muscle mass was significantly correlated with the ODI, VAS score, SVA, and EQ5D score (P

Background This multicenter retrospective study aimed to determine whether elective neck dissection (END) can be performed for T1-2N0M0 tongue cancer. Methods Patients with T1-2N0M0 tongue squamous cell carcinoma who received treatment between January 2000 and December 2012 were enrolled at 14 multicenter study sites. The 5-year overall survival (OS) and 5-year disease-specific survival (DSS) were compared between the propensity score-matched END and observation (OBS) groups. Results The results showed that the OS rates among the 1234 enrolled patients were 85.5% in the END group and 90.2% in the OBS group (P = 0.182). The DSS rates were 87.0% in the END group and 94.3% in the OBS group (P = 0.003). Among the matched patients, the OS rates were 87.1% in the END group and 76.2% in the OBS group (P = 0.0051), and the respective DSS rates were 89.2% and 82.2% (P = 0.0335). Conclusion This study showed that END is beneficial for T1-2N0M0 tongue cancer. However, END should be performed for patients with a tumor depth of 4–5 mm or more, which is the depth associated with a high rate of lymph node metastasis. The use of END should be carefully considered for both elderly and young patients.

The purpose of this study was to investigate and summarize our experience of a standardized strategy using computed tomography (CT) followed by colonoscopy for the assessment of colonic diverticular hemorrhage with focus on a comparison of CT and colonoscopy findings in patients with colonic diverticular hemorrhage.Colonic diverticular hemorrhage is usually diagnosed by colonoscopy, but it is difficult to identify the responsible bleeding point among many diverticula.We retrospectively included 257 consecutive patients with colonic diverticular hemorrhage. All patients underwent a CT examination before colonoscopy. All-cause mortality and rebleeding-free rate after discharge were analyzed by Kaplan-Meier analysis and compared using the log-rank test.In CT examinations, 184 patients (71.6%) had definite diverticular hemorrhage with 31.9% showing intraluminal high-density fluid on plain CT, 39.7% showing extravasation, and 31.1% showing arteriovenous increase of extravasation on enhanced CT. In colonoscopy, 130 patients (50.6%) showed endoscopic stigmata of bleeding with 12.1% showing active bleeding, 17.1% showing a nonbleeding visible vessel, and 21.4% showing an adherent clot. A comparison of the locations of bleeding in CT and colonoscopy showed that the agreement rate was 67.3%, and the disagreement rate was 0.8% when the lesion was identified by both modalities patients with definite diverticular hemorrhage identified by CT had a longer hospital stay, higher incidences of hemodynamic instability and rebleeding events than did patients with presumptive diverticular hemorrhage.CT evaluation before colonoscopy can be a good option for managing patients with colonic diverticular hemorrhage.

Background Selective plasma exchange (SePE) is a new simple plasma exchange (PE) modality that enables removal of small and medium-sized molecules without removing larger substances such as coagulation factors. In this study, we examined the efficacy of SePE for removal of isoagglutinins in pre-transplant desensitization for ABO-incompatible (ABOi) kidney transplantation. Materials and methods A case series study was performed in 15 ABOi kidney transplant recipients (KTRs) who underwent SePE alone (7 cases) and SePE in combination with double-filtration plasmapheresis or simple plasma exchange (8 cases). The target processed plasma volume (PV) was set at 2 PV, and 5% albumin solution was used as the substitution fluid in all SePE sessions. Changes in isoagglutinin titers (IgG and IgM) and serum IgG, IgM, and fibrinogen levels were examined. We also compared the decrease in isoagglutinin titers between SePE and conventional methods (PE and double-filtration plasmapheresis). Results A total of 29 sessions of SePE were performed in the 15 KTRs. Isoagglutinin titers were controlled to ≤ 1:16 in all patients except for 2 with high isoagglutinin titers, and there were no cases of antibody-mediated rejection. SePE led to a median twofold decrease in isoagglutinin titers (IgG and IgM), with median IgG, IgM, and fibrinogen removal rates of 64.2, 11.7, and 25.5%, respectively. Side effects occurred in only 4 of the 29 sessions. Neither titer decreased after SePE in 30% of the sessions. However, the reductions in isoagglutinin titers in patients undergoing SePE were significantly less than those in patients treated with conventional methods. Conclusion Because SePE is less efficient in removing isoagglutinins compared to conventional methods, the use of SePE alone should be limited to patients with low isoagglutinin titers, and SePE in combination with conventional methods should be used for patients with high isoagglutinin titers. SePE may be a useful treatment option, if applied in appropriate cases, due to its lower cost (about half the price of PE using fresh frozen plasma in Japan) and fewer side effects. However, care is required because about 25% of fibrinogen is removed during SePE.

Background: Pteridines are metabolites of tetrahydrobiopterin, which serves as co-enzyme of nitric oxide synthase. We sought to investigate the usefulness of pteridines as biomarkers for childhood asthma control. Methods: We conducted a single-center prospective cohort study involving 168 asthmatic children aged 4–17 years who visited the periodical asthma checkup program. Serum neopterin and biopterin levels were measured as pteridines at each visit along with measurement of FeNO, respiratory function tests, nasal eosinophil test, blood eosinophil count, and IgE level. We calculated coefficients for relation between pteridines and asthma control, which was assessed by questionnaires (JPAC: Japanese Pediatric Asthma Control Program). Results: A total of 168 participants aged 10.3 ± 3.39 years (mean ± SD) with asthma were recruited. The participants in this study contained 58 patients (34.5%) of complete-controlled based on JPAC, 132 patients (76.0%) of well-controlled group based on GINA. FeNO and serum neopterin level did not correlate with following period's JPAC scores. In contrast, serum biopterin level significantly correlated with following period's JPAC total score (Coefficients 0.398; 95% CI 0.164 to 0.632; p value 0.001) and frequency of wheezing during exercise (Coefficients 0.272; 95% CI 0.217 to 0.328; p value

Background/Aims: Vascular calcification is common and progressive in chronic kidney disease, including kidney transplant recipients (KTRs). However, the risk factors associated with the progression of aortic calcification (AoC) in KTRs have not been fully elucidated. In the present study, we evaluated AoC and examined the factors associated with its advancement in KTRs. Materials: This was a prospective longitudinal study that included 98 KTRs. We quantitatively investigated infrarenal abdominal AoC using the Agatston score, as measured by multi-slice computed tomography. After the baseline investigation, a follow-up scan was performed after 3 years, and the Agatston scores were obtained again. The changes in laboratory data affecting the 2nd Agatston scores were examined by multivariable analysis using non-linear regression after adjustment for several confounders. Results: The 2nd Agatston scores were significantly greater than the baseline Agatston scores (p < 0.001). After adjustment for the confounders, the change in corrected serum calcium exhibited a significant non-linear correlation with the 2nd Agatston scores (p = 0.022 for non-linearity/p = 0.031 for the effect of corrected serum calcium). Moreover, an interaction was present from the baseline AoC in the effect of corrected serum calcium on the progression of AoC, and the effect of hypercalcemia was greater in patients with higher baseline Agatston scores (p = 0.049). Conclusion: The present study revealed that hypercalcemia is a risk factor for the development of infrarenal abdominal AoC in KTRs. Furthermore, the effect of hypercalcemia was greater in patients with more severe vascular calcification.

The yips are a set of conditions associated with intermittent motor disturbances that affect precision movement, especially in sports. Specifically, skilled golfers suffer from the yips, although its clinical characteristics and pathophysiology have not been well-studied. We surveyed skilled golfers to characterize their yips-related symptoms, to explore potential confounding factors associated with the yips. Golfers’ demographic information, golfing-career-related history, musculoskeletal status and manifestations of the yips are surveyed. Among the 1576 questionnaires distributed, 1457 (92%) responses were received, of which 39% of golfers had experienced the yips. The median age and golfing careers were 48 and 28 years, respectively. Golfers who had experienced the yips were older and had longer golfing careers and more frequent musculoskeletal problems than those without experience of the yips. The multivariate logistic regression analysis revealed that a longer golfing career and musculoskeletal problems were independent factors associated with yips experience. More severe musculoskeletal problems were associated with higher odds of experiencing the yips. A positive association between the yips and musculoskeletal problems was also observed. The yips have similar characteristics to task-specific movement disorders, with a detrimental effect caused by excessive repetition of a routine task. These findings support the notion that the yips are a type of task-specific dystonia.

Background: Empagliflozin reduces the risk of hospitalization for heart failure in patients with type 2 diabetes and cardiovascular disease. We sought to elucidate the effect of empagliflozin as an add-on therapy on decongestion and renal function in patients with type 2 diabetes admitted for acute decompensated heart failure. Methods: The study was terminated early due to COVID-19 pandemic. We enrolled 59 consecutive patients with type 2 diabetes admitted for acute decompensated heart failure. Patients were randomly assigned to receive either empagliflozin add-on (n=30) or conventional glucose-lowering therapy (n=29). We performed laboratory tests at baseline and 1, 2, 3, and 7 days after randomization. Percent change in plasma volume between admission and subsequent time points was calculated using the Strauss formula. Results: There were no significant baseline differences in left ventricular ejection fraction and serum NT-proBNP (N-terminal pro-B-type natriuretic peptide), hematocrit, or serum creatinine levels between the 2 groups. Seven days after randomization, NT-proBNP level was significantly lower in the empagliflozin group than in the conventional group ( P =0.040), and hemoconcentration (≥3% absolute increase in hematocrit) was more frequently observed in the empagliflozin group than in the conventional group ( P =0.020). The decrease in percent change in plasma volume between baseline and subsequent time points was significantly larger in the empagliflozin group than in the conventional group 7 days after randomization ( P =0.017). The incidence of worsening renal function (an increase in serum creatinine ≥0.3 mg/dL) did not significantly differ between the 2 groups. Conclusions: In this exploratory analysis, empagliflozin achieved effective decongestion without an increased risk of worsening renal function as an add-on therapy in patients with type 2 diabetes with acute decompensated heart failure. Registration: URL: https://www.umin.ac.jp/ctr/index.htm ; Unique identifier: UMIN000026315.

Background: The yips are a set of conditions associated with intermittent motor disturbance that affects precision movement, especially in sports. Specifically, skilled golfers suffer from the yips, although its clinical characteristics and pathophysiology have not been well studied. Methods: The purpose of this study was aimed to conduct an epidemiological investigation and explore potential confounding factors associated with the yips among skilled golfers in Japan. We surveyed highly-skilled golfers for characterizing the yips-related symptoms. The survey comprised golfers’ demographic information, golfing-career-related history, musculoskeletal status, and manifestations of the yips. The answers obtained were statistically analyzed to examine the association between golf and the yips.Results: Among the 1,576 questionnaires distributed, 1,457 (92%) responded, of which 39% experienced the yips. The median age and golfing careers were 48 and 28 years, respectively. Golfers with the yips experience were older, had longer golfing careers, and more frequent musculoskeletal problems than those without the yips experience. The multivariate logistic regression analysis revealed that a longer golfing career [odds ratio (OR), 1.07; 95% confidence interval (CI), 1.04–1.11] and musculoskeletal problems (OR, 1.08; 95% CI, 1.03–1.13) were independent factors associated with the yips experience. More severe musculoskeletal problems were associated with higher odds of experiencing the yips. Changing the training method and/or hitting style were effective for improving the yips.Conclusions: Our results revealed that the yips has similar characteristics to task-specific movement disorders, with a detrimental effect caused by excessive repetition of a routine task and a positive association between the yips and musculoskeletal problems. These findings supported the notion that the yips is a type of task-specific dystonia.

Background and aims Brazilian propolis reportedly contributed to suppressing disease activity in a mouse model of rheumatoid arthritis (RA), suggesting new treatment options using Brazilian propolis. However, only results from animal experiments have been available, and the suppressive effects of Brazilian propolis on disease activity in humans with RA remain unknown. The purpose of this study was to clinically validate how Brazilian propolis intake changes disease activity in RA patients. Methods This study was conducted as a multicenter, double-blinded, randomized, placebo-controlled, parallel-group study of 80 women with RA (median age, 61.5 years; interquartile range, 56.0 to 67.3 years) showing moderate disease activity on Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR). Test tablets containing Brazilian propolis were used in Group P (40 patients), and Brazilian propolis-free placebo tablets were used as control in Group C (40 patients). Group P received 5 tablets of propolis (508.5 mg of propolis) daily, and Group C received 5 tablets of placebo daily. The intervention lasted 24 weeks, with change in DAS28-ESR set as the primary endpoint. As secondary endpoints, other disease activity assessment (DAS28 using C-reactive protein, simplified disease activity index, clinical disease activity index), ultrasonographic evaluation of synovitis, activities of daily living, quality of life, changes in cytokine levels, and adverse events over the course of the study were also assessed. Data were statistically analyzed by analysis of covariance. Results No significant differences in the primary endpoint were identified between groups (Group P vs Group C, effect: 0.14, 95% confidence interval: -0.21 to 0.49, p = 0.427). Likewise, no significant differences were seen between groups for any secondary endpoints. The adverse event rate during the study period was 28% in Group P and 33% in Group C. Conclusions Brazilian propolis exerted no effects on disease activity in patients with RA.

Favipiravir is an oral broad-spectrum inhibitor of viral RNA-dependent RNA polymerase that is approved for treatment of influenza in Japan. We conducted a prospective, randomized, open-label, multicenter trial of favipiravir for the treatment of COVID-19 at 25 hospitals across Japan. Eligible patients were adolescents and adults admitted with COVID-19 who were asymptomatic or mildly ill and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients were randomly assigned at a 1:1 ratio to early or late favipiravir therapy (in the latter case, the same regimen starting on day 6 instead of day 1)., Favipiravir is an oral broad-spectrum inhibitor of viral RNA-dependent RNA polymerase that is approved for treatment of influenza in Japan. We conducted a prospective, randomized, open-label, multicenter trial of favipiravir for the treatment of COVID-19 at 25 hospitals across Japan. Eligible patients were adolescents and adults admitted with COVID-19 who were asymptomatic or mildly ill and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients were randomly assigned at a 1:1 ratio to early or late favipiravir therapy (in the latter case, the same regimen starting on day 6 instead of day 1). The primary endpoint was viral clearance by day 6. The secondary endpoint was change in viral load by day 6. Exploratory endpoints included time to defervescence and resolution of symptoms. Eighty-nine patients were enrolled, of whom 69 were virologically evaluable. Viral clearance occurred within 6 days in 66.7% and 56.1% of the early and late treatment groups (adjusted hazard ratio [aHR], 1.42; 95% confidence interval [95% CI], 0.76 to 2.62). Of 30 patients who had a fever (≥37.5°C) on day 1, times to defervescence were 2.1 days and 3.2 days in the early and late treatment groups (aHR, 1.88; 95% CI, 0.81 to 4.35). During therapy, 84.1% developed transient hyperuricemia. Favipiravir did not significantly improve viral clearance as measured by reverse transcription-PCR (RT-PCR) by day 6 but was associated with numerical reduction in time to defervescence. Neither disease progression nor death occurred in any of the patients in either treatment group during the 28-day participation. (This study has been registered with the Japan Registry of Clinical Trials under number jRCTs041190120.)

Objective Home care is important in patients with heart failure (HF) in order to maintain their quality of life. A biomarker that can be measured noninvasively is needed to optimize the home care of patients with HF. Urinary angiotensinogen (uAGT) is an indicator of the intrarenal renin-angiotensin system activity, which may be augmented in HF. We hypothesized that uAGT might be a urinary biomarker in HF. Methods We measured uAGT by an enzyme-linked immunosorbent assay and uAGT normalized by urinary creatinine (uCr)-designated uAGT/uCr-at admission and discharge in 45 patients hospitalized for HF. Results We found that both uAGT/uCr [median (interquartile range): 65.5 (17.1-127.7) μg/g Cr at admission; 12.1 (6.0-37.0) μg/g Cr at discharge; p

Background Smoking predisposes individuals to endothelial dysfunction. Both flow-mediated dilation (FMD) and reactive hyperemia peripheral artery tonometry (RH-PAT) are used to assess endothelial function. However, there are differences in the physiology of vascular beds being tested and in the response of conduit and resistive vessels to RH. Therefore, whether smoking cessation demonstrates comparable effects on endothelial function evaluated by FMD and by RH-PAT remains unclear. Purpose We aimed to evaluate the effects of smoking cessation on endothelial function evaluated simultaneously by FMD and RH-PAT. Methods Thirty-eight consecutive current smokers (mean±standard deviation; age, 65±10 years) who visited our smoking cessation outpatient department and succeeded in smoking cessation with varenicline were enrolled. Clinical variables, FMD, and natural logarithmic transformation of the reactive hyperemia index (Ln-RHI) were examined before and 20 weeks after treatment initiation. Fifteen current smokers who failed in smoking cessation were enrolled as age- and sex-matched controls. The Spearman's rank correlation coefficient and intraclass correlation coefficient (ICC) for a two-way mixed effects model were performed to assess the agreement of changes in FMD and Ln-RHI. Multivariate logistic regression analysis was performed to examine the associations between the presence of increase in FMD or Ln-RHI and clinical variables. Results FMD significantly improved after smoking cessation (3.42%±1.96% to 4.45%±2.28%; p=0.019), whereas Ln-RHI did not (0.53±0.25 to 0.59±0.21; p=0.223). The Spearman's rank correlation coefficient between changes in FMD and Ln-RHI was −0.013, and the ICC was −0.002 (p=0.506). In the multivariate logistic regression analysis, an increase in FMD or Ln-RHI was predicted based on the baseline FMD (odds ratio = 0.54, p=0.013) or Ln-RHI (odds ratio = 0.36, p=0.012), respectively, after adjusting for age and sex. Conclusions There was significant improvement in the endothelial function assessed by FMD, but not by Ln-RHI, after smoking cessation. In addition, there was disagreement between changes in FMD and those in Ln-RHI. Smoking cessation may have varying effects on the endothelial function of the conduit and digital vessels. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Grant-in-aid for scientific research from the ministry of education, science and culture of Japan

Background: The impact of pancreas transplantation, including kidney transplantation on patients&rsquo, life prognoses, is unclear in Japan. An analysis of the data of the Japan Pancreas Transplant Registry was performed to compare the patient survival between on the waiting list and after pancreas transplantation, and investigate the factors that affect the patient survival after pancreatic transplantation. Methods: The life prognoses of 361 patients who underwent pancreas transplantation from 2000 to December 2018 were examined. Results: The survival rates at 1, 5, and 10 years on the waiting list were 98.4%, 90.3%, and 78.1%, respectively, while those after transplantation were significantly improved (p = 0.029) at 100%, 97.5%, and 88.9%, respectively. Furthermore, the survival rates of patients waiting for simultaneous pancreas and kidney transplantation (SPK) at 1, 5, and 10 years were 98.2%, 89.4%, and 75.4%, respectively, while those after SPK were also significantly improved (p = 0.026) at 100%, 94.6%, and 88.8%. The multivariable analysis revealed that the duration of diabetes before surgery was the only independent risk factor (hazard ratio = 1.095, p = 0.012) that affected the patient survival after SPK. Conclusion: Pancreas transplantation was found to improve the life prognosis of patients with type 1 diabetes, especially those with end-stage renal failure waiting for SPK.

There are few studies developing a scoring system for short-term survival of patients with gynecologic malignancy. Seventy-three terminally ill patients with gynecologic malignancy who were admitted to our palliative care unit (PCU) from June 2009 to February 2018 were included. We accumulated routine blood data within 3 months before PCU discharge. Receiver-operating characteristic analysis was performed on each blood factor, and area under the curve (AUC) was calculated to determine the predictive value for 14-day survival after the blood test. Multivariable logistic regression analysis was performed to identify significant independent prognostic factors of 14-day mortality. To develop a scoring system for 14-day mortality, laboratory prognostic score for gynecologic malignancy (G-LPS) was calculated using the sum of indices of the independent prognostic factors. Multivariable analysis showed that 6 of 24 indices, namely, C-reactive protein ≥ 13.3 mg/dL, total bilirubin ≥ 1.1 mg/dL, sodium

Background and Aims Repeated needle pain during haemodialysis (HD) access cannulations is a serious problem for HD patients. Although the efficacy of music for alleviating pain and anxiety is well established, there is insufficient scientific evidence related to its effectiveness in alleviating pain during access cannulations during HD. This study aimed to investigate the effects of music on reducing pain during access cannulating in HD patients. Method A prospective, multi-facility, single-blind, crossover, randomised controlled trial was conducted. The intervention included listening to Mozart and a white-noise control condition. Patients were randomly allocated to either an ‘Early-group’ or a ‘Later-group’. All patients who underwent cannulation wore headphones without sound in the first and third weeks (No-sound period). The Early-group received cannulation while listening to Mozart’s Sonata for Two Pianos in D major (K.448) during the second week (Music period), and white noise during the fourth week (White noise period). The Later-group received cannulation while listening to white noise first, followed by Mozart in the fourth week. During each period, the music or no-music protocol started 8 minutes prior to the cannulation, and participants finished listening after HD began. The Visual Analogue Scale (VAS) was used to measure pain and anxiety during cannulation and the VAS scores for pain and anxiety were compared for the music and no-music settings. We evaluated the ratio of outcome measures between the music and white noise periods with the repeated measure mixed effect regression. We analysed the effects according to the intention-to-treat principle. Two-sided-significance-level was set at 0.05. Results In total, one hundred and twenty-one patients were enrolled in this study, across four facilities. The median age was 64 years, and there were 84 males (69.4%). Sixty-five patients (53.7%) used analgesics for alleviating pain. The median VAS pain score was 28 and VAS anxiety score was 19 in No-sound period. The Mozart music setting had a 12.2% (95% confidence interval (CI): 2.3 to 21.1, p=0.017) lower VAS score than the white noise setting. On the other hand, there was no significant difference in the VAS anxiety score between the two groups, that is the Mozart music setting had a 7.96% (95% CI: -4.70 to 18.4, p=0.172) reduction compared to the white noise setting. Conclusion We examined the effects of Mozart’s music on alleviating pain using scientific methods. The music appears to reduce pain of access cannulation in HD patients. Although the trial assessed the effects of music using a single musical composition, the study did not clarify the effects of music on the physical, emotional, and cognitive status of patients. Further studies in this direction are required.

Smoking predisposes individuals to endothelial dysfunction. Flow-mediated dilation (FMD) and reactive hyperemia peripheral artery tonometry (RH-PAT) are used to assess endothelial function. However, whether smoking cessation demonstrates comparable effects on endothelial function evaluated by FMD and RH-PAT remains unclear. Thus, we aimed to evaluate the effects of smoking cessation on endothelial function evaluated simultaneously by FMD and RH-PAT and clarify the factors associated with these effects. Fifty-eight consecutive current smokers (mean ± standard deviation; age, 64 ± 11 years) who visited our smoking cessation outpatient department and succeeded with smoking cessation were enrolled. Twenty-one continued smokers were enrolled as age- and sex-matched controls. Clinical variables, FMD, and natural logarithmic transformation of the reactive hyperemia index (Ln-RHI) were examined before and 20 weeks after treatment initiation. In 58 smokers who succeeded with smoking cessation, FMD significantly improved (3.80 ± 2.24 to 4.60 ± 2.55%; p = 0.013), whereas Ln-RHI did not (0.59 ± 0.28 to 0.66 ± 0.22; p = 0.092). Spearman’s rank correlation coefficient between changes in FMD and Ln-RHI was −0.004, and the intraclass correlation coefficient for a two-way mixed effects model was

Introduction Polymyxin B hemoperfusion (PMX-HP) is an adjuvant therapy for sepsis or septic shock that removes circulating endotoxin. However, PMX-HP has seldom achieved expectations in randomized trials targeting nonspecific overall sepsis patients. If used in an optimal population, PMX-HP may be beneficial. This study aimed to identify the optimal population for PMX-HP in patients with septic shock. Methods We used a prospective nationwide cohort targeting consecutive adult patients with severe sepsis (Sepsis-2) in 59 intensive care units in Japan. Associations between PMX-HP therapy and in-hospital mortality were assessed using multivariable Cox proportional hazard regression models. To identify best targets for PMX-HP, we developed a non-linear restricted cubic spline model including two-way interaction term (treatment × Acute Physiology and Chronic Health Evaluation [APACHE] II score/Sequential Organ Failure Assessment [SOFA] score) and three-way interaction term (treatment × age × each score). Results The final study cohort comprised 741 sepsis patients (92 received PMX-HP, 625 did not). Cox proportional hazards regression model adjusted for the covariates suggested no association between PMX-HP therapy and improved mortality overall. Effect modification of PMX-HP by APACHE II score was statistically significant (P for interaction = 0.189) but non-significant for SOFA score (P for interaction = 0.413). Three-way interaction analysis revealed suppressed risk hazard in the PMX-HP group versus control group only in septic shock patients with high age and in the most severe subset of both scores, whereas increased risk hazard was observed in those with high age but in the lower severity subset of both scores. Conclusions Our results suggested that although PMX-HP did not reduce in-hospital mortality among overall septic shock patients, it may benefit a limited population with high age and higher disease severity.

We have performed selective plasma exchange (SePE) as apheresis before ABO-incompatible kidney transplantation since 2015. In this study, we divided the SePE sessions into two groups, those using albumin alone (Group A) and those partially using fresh frozen plasma (FFP) (Group F), and compared their clinical efficacies. A total of 58 sessions of SePE (Group A: n = 41, Group F: n = 17) were performed in 30 recipients of ABOi kidney transplantation during the study period and the decrease in isoagglutinin titers, changes in the levels of serum IgG and IgM as well as coagulation factors (fibrinogen, factor XIII), and incidence of side effects were retrospectively compared. There was a more significant decrease of isoagglutinin titers in Group F compared to Group A. Immunoglobulins and coagulants were replenished in Group F. Meanwhile, the incidence of side effects was significantly higher in Group F. SePE using FFP, which can effectively decrease isoagglutinins titers and replenish immunoglobulin and coagulation factors, may be a beneficial treatment modality as apheresis before ABO-incompatible kidney transplantation, in spite of a disadvantage that there are many side effects.

Background The present study aimed to examine whether variables including D-dimer, high-sensitivity C-reactive protein (hsCRP), hemoglobin, platelet count, and nutritional status mediate the pathway between cancer and ischemic stroke outcomes. Methods We reviewed data from consecutive patients with ischemic stroke admitted to Osaka University Hospital between January 1, 2006, and December 31, 2016. Patients with ischemic stroke were grouped according to the presence of cancer. Nutritional status was assessed using Controlling Nutritional Status (CONUT) scores. Mediation analyses were utilized to address the study aims. Results Among 1,570 patients with ischemic stroke, 185 (12%) had active cancer. Relative to patients with ischemic stroke in the non-cancer group, those in the cancer group exhibited higher National Institutes of Health Stroke Scale scores on admission, higher D-dimer and hsCRP levels, lower hemoglobin levels and platelet counts, higher CONUT scores, and poorer modified Rankin Scale scores at discharge. Mediation analysis revealed that D-dimer, hsCRP, hemoglobin, platelet count, and CONUT scores acted as mediators of poor prognosis in the cancer group. The association between the exposure and outcome variables was no longer significant in the models containing D-dimer and CONUT scores as mediator variables, suggesting that they were strong mediators. Regarding the association between the mediator and outcome variables, hemoglobin, platelet count, and CONUT exhibited non-linearity (p for non-linearity Conclusions D-dimer, hsCRP, hemoglobin, platelet count, and CONUT score act as mediators of poor prognosis in patients with ischemic stroke with comorbid cancer. Such abnormalities can help to predict ischemic stroke outcomes.

Objective: Recent guidelines propose that both proton pump inhibitor (PPI) responders and nonresponders are included in eosinophilic esophagitis (EoE). Although multiple biopsies should be required to diagnose EoE because of patchy distribution of esophageal eosinophils, it is unclear whether multiple biopsies are required to evaluate histological effectiveness of PPI therapy. This study aimed to determine the optimal biopsy protocol after PPI therapy in patients with EoE. Methods: Of 110 EoE patients, 22 PPI nonresponders were enrolled. Intraepithelial eosinophils were counted in areas of high density in multiple biopsy specimens after PPI therapy. The prevalence of esophageal eosinophilia and peak eosinophil counts after PPI therapy was analyzed according to the biopsy sites and endoscopic findings. Positive predictive value (PPV) was calculated according to the number of biopsies. Results: Of 124 biopsies, 59 (47.6%) specimens showed esophageal eosinophilia (≥15 per high-power field). Eosinophil counts were significantly higher in specimens from the lower esophagus than in those from the upper esophagus but not in those from the middle esophagus. Prevalence of esophageal eosinophilia was 76.2, 40.9, and 24.3% in the lower, middle, and upper esophagus respectively. PPI nonresponders were diagnosed in all cases with 4 biopsy specimens obtained from the lower and middle esophagus, showing that PPV for non-effectiveness of PPI therapy was 0.910 (95% CI 0.773–1.000). The prevalence of esophageal eosinophilia and peak eosinophil counts was higher in cases with white plaques and linear furrows. Conclusion: Multiple biopsies should be required to evaluate histological effectiveness of PPI therapy in patients with EoE. Four biopsies from the lower and middle esophagus may be sufficient.