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A 40-year-old Japanese woman developed malignant-phase hypertension complicated by thrombotic microangiopathy, progressing to end-stage renal disease. Five years later, she was diagnosed with pulmonary arterial hypertension and interstitial pneumonia. Despite a lack of overt skin sclerosis, nucleolar staining in our indirect immunofluorescence analysis and nailfold capillaroscopy facilitated the diagnosis of anti-PM/Scl antibody-positive systemic sclerosis. We observed the persistent presence of anti-PM/Scl antibodies throughout the clinical course, suggesting that her kidney disease was scleroderma renal crisis. Anti-PM/Scl antibodies can be associated with multiple organ diseases. Careful attention to a patient's antinuclear antibody pattern and dermatological findings may help clarify the etiology of undiagnosed diseases.

This meta-analysis aimed to evaluate the device performance of conventional balloon catheters (POBA), drug-coated balloons (DCB), bare-metal stents (BMS), and drug-eluting stents (DES) in below-the-knee (BTK) ischemic lesions with regard to lesion characteristics. Online searches of PubMed, Web of Science, and Cochrane databases (2010–2019) were conducted for each of the test devices. Primary patency rates (pp) and major amputation rates 1 year after the use of each device were analyzed using a random-effects meta-analysis model. Meta-regression analysis was conducted to test associations between the outcomes and lesion characteristics. The analysis included 18 studies reporting on 24 separate cohorts comprising 2,438 patients. DES demonstrated the best pp among the test devices (83.6%; 95% confidence interval = 78.4–88.8%, studies = 8; I2 = 66%, P = 0.005). A negative coefficient between lesion length and pp (P = 0.002) was obtained. The ratio of critical limb ischemia (CLI) patients impacted the amputation rates (P = 0.031), whereas no statistically significant difference was found between the devices. DES showed favorable pp in BTK lesions; however, as the lesion lengths using DES were short, pp in long lesions still needs to be evaluated. Shorter lesions gained better pp. A higher ratio of CLI patients resulted in increased amputation rates.

Study Design: Single-center retrospective study.Purpose: We aimed to explore the postoperative prognostic factors for spinal intramedullary ependymoma.Overview of Literature: Ependymoma (World Health Organization grade II) is the most frequent intramedullary spinal tumor and is treated by total resection. However, postoperative deterioration of motor function occasionally occurs.Methods: Eighty patients who underwent surgical resection at Keio University and Fujita Health University in Tokyo, Japan between 2003 and 2015 with more than 2 years of follow-up were enrolled. A good surgical result was defined as an improvement in the modified McCormick Scale score by one grade or more or having the same clinical grade as was observed preoperatively. Meanwhile, a poor result was defined as a reduction in the McCormick Scale score of one grade or more or remaining in grade IV or V at final follow-up. Univariate and multivariate logistic regression analyses of the following factors were performed in the two groups: sex, age, preoperative Visual Analog Scale (VAS), tumor location, the extent of tumor resection, hemosiderin caps, cavity length, and tumor length on magnetic resonance imaging.Results: At final follow-up, 15 patients were included in the poor results group and 65 in the good results group. In the univariate analysis, the factors related to poor results were as follows: higher age, preoperative McCormick Scale score severity, higher preoperative VAS, thoracic location, hemosiderin capped, and non-gross total resection (GTR). A multiple logistic regression analysis was conducted and showed that age, worse preoperative McCormick Scale score, and non-GTR were significant factors for poor prognosis.Conclusions: The independent risk factors for motor deterioration after ependymoma resection were age, worse preoperative McCormick Scale score, and non-GTR. Early surgery for patients with even mild neurological disorders could facilitate functional outcomes. These results may contribute to determining the optimal timing of surgery for spinal intramedullary ependymoma.

A 28-year-old woman was admitted during the eighth week of her pregnancy because her clinical course was consistent with rapid progressive glomerulonephritis (RPGN). Anti-glomerular basement membrane antibody (anti-GBM Ab) and myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) were positive, and the anti-GBM Ab titer being extremely high. She was treated with hemodialysis, plasma exchange and prednisolone. She survived the illness; however, neither the fetus nor her kidney function could be rescued. She had human leukocyte antigen (HLA)-DRB1*1502:01, which differs from the DRB1*1501 associated with anti-GBM GN. When patients have particular symptoms, we should check the urine and serum creatinine to exclude RPGN, even in cases of pregnancy.

Case report: an 80-year-old woman presented with rapidly progressive glomerulonephritis and was admitted to our hospital. Myeloperoxidase-specific antineutrophil cytoplasmic antibody (MPO-ANCA) was positive. We diagnosed ANCA-associated renal vasculitis (ANCA-RV). Treatment was initiated with intravenous methylprednisolone pulse therapy, followed by prednisolone (PSL) at 30 mg/day. We gradually reduced the PSL dose to 7.5 mg/day over 6 months. At that time, the patient developed disturbances of consciousness which progressed subacutely. MRI revealed regions of patchy white matter with an increased signal on T2-weighted, fluid attenuated inversion recovery (FLAIR) sequences and diffusion-weighted sequences. JC virus DNA was detected in the cerebrospinal fluid (CSF) by polymerase chain reaction (PCR), leading to a diagnosis of progressive multifocal leukoencephalopathy (PML). PML is a rare infectious demyelinating disease of the central nervous system caused by JC virus infection, occurring in highly immunosuppressed individuals such as HIV-infected patients and patients using some biological agents, and having a very poor prognosis. In the present case, PML may have been associated with steroid use, although there are very few case reports of PML in patients taking only steroids. We report progressive multifocal leukoencephalopathy during steroid treatment of ANCA-RV. When patients show progressive disturbance of consciousness during treatment for ANCA-RV, we need to take PML into consideration for differential diagnosis.

Background The Response Evaluation Criteria in Solid Tumors (RECIST) for computed tomography (CT) is preoperatively used to evaluate therapeutic effects. However, it does not reflect the pathological treatment response (PTR) of pancreatic ductal adenocarcinoma (PDAC). The Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) for positron emission tomography (PET)/CT is effective in other cancers. This study aimed to confirm the usefulness of PERCIST and the prognostic utility of PET/CT for PDAC. Methods Forty‐two consecutive patients with PDAC who underwent neoadjuvant therapy (NAT) and pancreatectomy at our institution between 2014 and 2018 were retrospectively analyzed. We evaluated the treatment response and prognostic significance of PET/CT parameters and other clinicopathological factors. Results Twenty‐two patients who underwent PET/CT both before and after NAT with the same protocol were included. RECIST revealed stable disease and partial response in 20 and 2 cases, respectively. PERCIST revealed stable metabolic disease, partial metabolic response, and complete metabolic response in 8, 9, and 5 cases, respectively. The PTR was G3, G2, and G1 in 8, 12, and 2 cases, respectively. For comparing the concordance rates between PTR and each parameter, PERCIST (72.7% [16/22]) was significantly superior to RECIST (36.4% [8/22]) (P = .017). The area under the curve survival values of PET/CT parameters were 0.777 for metabolic tumor volume (MTV), 0.500 for maximum standardized uptake value, 0.554 for peak standardized uptake value corrected for lean body mass, and 0.634 for total lesion glycolysis. A 50% cut‐off value for the MTV reduction rate yielded the largest difference in survival between responders and nonresponders. On multivariate analysis, MTV reduction rates, 18F‐fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) was more accurate in determining the therapeutic effects of neoadjuvant therapy for pancreatic ductal adenocarcinoma than CT, which detects anatomical changes. The reduction rate of the PET/CT parameter was an independent prognostic factor for pancreatic ductal adenocarcinoma.

With ageing, normal human tissues experience an expansion of somatic clones that carry cancer mutations1-7. However, whether such clonal expansion exists in the non-neoplastic intestine remains unknown. Here, using whole-exome sequencing data from 76 clonal human colon organoids, we identify a unique pattern of somatic mutagenesis in the inflamed epithelium of patients with ulcerative colitis. The affected epithelium accumulates somatic mutations in multiple genes that are related to IL-17 signalling-including NFKBIZ, ZC3H12A and PIGR, which are genes that are rarely affected in colon cancer. Targeted sequencing validates the pervasive spread of mutations that are related to IL-17 signalling. Unbiased CRISPR-based knockout screening in colon organoids reveals that the mutations confer resistance to the pro-apoptotic response that is induced by IL-17A. Some of these genetic mutations are known to exacerbate experimental colitis in mice8-11, and somatic mutagenesis in human colon epithelium may be causally linked to the inflammatory process. Our findings highlight a genetic landscape that adapts to a hostile microenvironment, and demonstrate its potential contribution to the pathogenesis of ulcerative colitis.

Objectives The aims of this study were to evaluate the feasibility of quantitative synthetic magnetic resonance imaging (SyMRI) for characterizing bone lesions in prostate cancer and to discriminate viable progressive osteoblastic bone metastasis from nonviable bone metastases with treatment-induced sclerosis during the treatment course. Materials and Methods This institutional review board-approved prospective study included 96 consecutive prostate cancer patients who underwent whole-body MRI including diffusion-weighted imaging at the time of staging at diagnosis or starting a new line of anticancer treatment. Additional synthetic MRI of the lumbosacral spine, pelvis, and proximal femurs was performed. A region of interest of 1.0 cm in diameter was set in each bone lesion by 2 independent readers who were blinded to bone lesions' diagnosis. Differences in SyMRI variables between the different bone lesions were compared with the Wilcoxon rank sum test, and associations of SyMRI variables with active disease were analyzed with logistic regression analysis. Performance of T1, T2, and proton density (PD) for diagnosing active disease was assessed using the area under the receiver operating characteristic curve. Results Ninety-three bone lesions were eligible for analysis. The PD values of active (viable) bone metastatic lesions were significantly higher than those of inactive (nonviable) bone metastatic lesions without sclerosis and those of red bone marrow (P

A retrospective cohort study OBJECTIVE: To establish a logarithmic model to predict functional independence after spinal cord injury.The National Hospital Organization, Murayama Medical Center, Japan.Thirty-one adults with a traumatic spinal cord injury (SCI) were enrolled. The Spinal Cord Independence Measure (SCIM) III scores obtained at month 1 and 3 after admission were used to construct a simple logarithmic model to predict SCIM III scores. The validity of the predicted scores was evaluated using a linear mixed model, and agreement between the predicted and measured scores were assessed using the Bland-Altman analysis.In the linear mixed model, the fixed effect slope [95% CI] and the intercept [95% CI] were 1.18 [0.78, 1.58] and -1.75 [-10.3, 6.83], respectively. The scatter plot showed non-linear correlation between the predicted and actual SCIM III scores. This non-linearity became inconspicuous when Sphincter Management scores were omitted. The fixed effect slope and the intercept were 1.12 [0.89, 1.36] and -1.64 [-4.95, 1.68], respectively. A significant fixed or proportional bias was not identified on the Bland-Altman analysis of the total SCIM III score, with most scores lying between an upper limit of +15.3 and a lower limit of -19.3.The logarithmic model provided an accurate prediction of the functional independence score of individuals with SCI in our cohort which included various neurological levels and severity of the injury. Along with its simplicity, our prediction model could be useful in daily practice.

Purpose: To investigate the utility of post-acquisition computed diffusion-weighted imaging (cDWI) for primary prostate cancer (PCa) evaluation in biparametric whole-body MRI (bpWB-MRI).Methods: Patients who underwent pelvic MRI for PCa screening and subsequent bpWB-MRI for staging were included.Two radiologists assessed the diagnostic performance of the following datasets for clinically significant PCa diagnosis (grade group >= 2 according to the Prostate Imaging-Reporting and Data System, version 2.1): bpMRI(2000) (axial DWI scans with a b-value of 2,000 s/mm(2) + axial T2WI scans from pre-biopsy pelvic MRI), computed bpWB-MRI2000 (computed WB-DWI scans with a b-value of 2,000 s/mm(2) + axial WB-T2WI scans), and native bpWB-MRI1000 (native axial WB-DWI scans with a b-value of 1,000 s/mm(2) + axial WB-T2WI scans). Systemic biopsy was used as reference standard.Results: Fifty-one patients with PCa were included. The areas under the curve (AUCs) of bpMRI(2000) (0.89 for reader 1 and 0.86 for reader 2) and computed bpWB-MRI2000 (0.86 for reader 1 and 0.83 for reader 2) were significantly higher (p < 0.001) than those of native bpWB-MRI1000 (0.67 for both readers). No significant difference was observed between the AUCs of bpMRI(2000) and computed bpWB-MRI2000 (p = 0.10 for reader 1 and p = 0.25 for reader 2).Conclusions: The diagnostic performance of computed bpWB-MRI2000 was similar to that of dedicated pelvic bpMRI(2000) for primary PCa evaluation. cDWI can be recommended for implementation in standard WB-MRI protocols to facilitate a one-step evaluation for concurrent detection of primary and metastatic PCa.

Objectives: To investigate the clinical utility of the Vesical Imaging-Reporting and Data System (VI-RADS) by comparing its diagnostic performance for muscle-invasive bladder cancer (MIBC) between radiologists and urologists based on multiparametric MRI, including three-dimensional (3D) fast spin-echo (FSE) T2-weighted acquisitions. Methods: This study included 66 treatment-naïve patients (60 men, 6 women; mean age 74.0 years) with pathologically proven bladder cancer who underwent multiparametric MRI, including 3D FSE T2-weighted imaging, before transurethral bladder tumour resection between January 2010 and November 2018. The MRI scans were categorised according to the five-point VI-RADS score by four independent readers (two board-certified radiologists and board-certified urologists each), blinded to the histopathological findings. The VI-RADS scores were compared with the postoperative histopathological diagnosis. Interobserver agreement was assessed using weighted kappa coefficients. ROC analysis and generalised estimating equations were used to evaluate the diagnostic performance. Results: Forty-nine (74.2%) and 17 (25.8%) tumours were confirmed to be non-MIBC and MIBC, respectively, based on pathological examination. The interobserver agreement was good-to-excellent between all pairs of readers (range, 0.73–0.91). The urologists’ sensitivity/specificity values for DCE-MRI VI-RADS scores were significantly lower than those of radiologists. No significant differences were observed for the overall VI-RADS score. The AUC for the overall VI-RADS score was 0.94, 0.92, 0.89, and 0.87 for radiologists 1 and 2 and urologists 1 and 2, respectively. Conclusions: The VI-RADS score, based on multiparametric MRI including 3D FSE T2-weighted acquisitions, can be useful for radiologists and urologists to determine the bladder cancer muscle invasion status preoperatively. Key Points: • VI-RADS (using multiparametric MRI including 3D FSE T2-weighted acquisitions) achieves good to excellent interobserver agreement and has similar diagnostic performance for detecting muscle invasion by both radiologists and urologists. • The diagnostic performance of the overall VI-RADS score is high for both radiologists and urologists, particularly due to the dominant effect of diffusion-weighted imaging on the overall VI-RADS score. • The sensitivity and specificity values of the T2WI VI-RADS scores for four readers in our study (using 3D FSE T2-weighted acquisitions) were similar (with slightly higher specificity values) to previously published results (using 2D FSE T2-weighted acquisitions).

Fetal fractional limb volume is a useful measure for predicting birth weight and newborn adiposity, however, a normal growth curve has been reported solely in the United States. As the birth weight of neonates in Japan is significantly lower than that in the US, fetal fractional limb volume is likely to be smaller in the Japanese population. This study aimed to define the normal growth curve of fractional arm volume (AVol) and thigh volume (TVol) in the Japanese population. Ultrasound scans of 453 AVol and TVol pairs were obtained, each AVol and TVol percentile at each gestational age was calculated. The measured AVol and TVol at each gestational week were also converted to z-scores based on a previous report. The growth curves increased linearly until the second trimester and exponentially in the third trimester. Linear regression showed a significant negative correlation between gestational age and AVol and TVol z-scores. The growth pattern of fetal fractional limb volume in the Japanese population is consistent with, but smaller than, that reported in the US, this difference becomes greater as the gestational age progresses.

Background and Purpose: Limited research has been conducted with the aim of understanding which upper extremity movements are difficult for persons with severe chronic stroke. The purpose of this study was to test the structure of the Fugl-Meyer Assessment for Upper Extremity (FMA-UE) using Rasch analysis in persons with chronic stroke with moderate to severe deficits and to determine the item difficulty hierarchy. Methods: This was a secondary analysis of data from previous randomized, controlled trials, or clinical trials. The participants were 101 persons with chronic stroke with moderate to severe hemiparesis (time after onset of stroke, 1375.3 ± 1157.9 days; the 33-item FMA-UE, 31.1 ± 12.8). Principal component analysis and infit statistics were used to evaluate dimensionality. Rasch analysis using a rating scale model was performed, and item difficulty was determined. Results: Six misfit items were removed. The results showed that the 27-item FMA-UE was unidimensional. Rasch analysis showed that the movements performed within synergies were among the easiest items. Shoulder and elbow movements were among the easiest items, whereas forearm and wrist movements were among the moderately to most difficult items. Hand items spanned various difficulty levels. Discussion and Conclusions: The FMA-UE is a valid assessment tool of upper extremity motor function in persons with chronic stroke with moderate to severe deficits. The results showed that item difficulty was consistent with the stepwise recovery course proposed by Fugl-Meyer. The movements that are difficult for patients with moderate to severe chronic paresis were determined, which would enable comparison of each movement using a measure of motion difficulty in future studies.

OBJECTIVE Fetal fractional limb volume has been proposed as a useful measure for quantifying fetal soft tissue development. The aim of this study was to investigate the growth of fractional arm volume (AVol) and fractional thigh volume (TVol) of fetuses with maternal gestational diabetes (GDM) compared with those of fetuses with normal glucose tolerance (NGT). We hypothesised fetal fractional limb volume would be larger in the GDM group than in the NGT group in late gestation. DESIGN Exploratory observational study. SETTING Saitama Municipal Hospital. SAMPLE A total of 165 (125 NGT and 40 GDM) singleton Japanese pregnant women. METHODS AVol and TVol were assessed between 20 and 37 weeks' gestation as cylindrical limb volumes based on 50% of the fetal humeral or femoral diaphysis length. Women were diagnosed as GDM based on the criteria of the Japan Society of Obstetrics and Gynecology. MAIN OUTCOME MEASURES AVol and TVol were compared between women with NGT and those with GDM at each gestational age period (2-week intervals from 20 to 37 weeks' gestation). RESULTS Overall, 287 ultrasound scans were performed (NGT group, 205 scans; GDM group, 82 scans). There was no significant difference of AVol between the groups before 32 weeks' gestation. AVol was significantly larger in the GDM group than in the NGT group after 32 weeks' gestation (P

–Accelerated failure time (AFT) models give an intuitive estimator for survival data analysis, but there is a risk of model misspecification. As a serious problem of model misspecification, the test size is likely to be far from the nominal level. Many researchers provided asymptotic corrections of various test statistics under model misspecification. However, their corrected statistics do not have good performance in small samples; in particular, they cause an inflation of test size. Although, the Bartlett adjustment is a popular approach for small-sample correction of the likelihood ratio statistic under the null hypothesis, it is impossible to derive the adjustment factor analytically under model misspecification. In this article, we proposed a robust test to model misspecification in small samples. Our proposed method is based on the Bartlett adjustment and we used the nonparametric bootstrap method to estimate the adjustment factor. We applied the proposed method to the AFT models when the error distribution and/or mean structure are misspecified in small samples. Our simulation results showed that the test size for the proposed method was close to the nominal level, although the existing methods resulted in substantial inflation of the test size. We illustrated our proposed method using two empirical examples.

While planning clinical trials, when simple formulas are unavailable to calculate sample size, statistical simulations are used instead. However, one has to spend much computation time obtaining adequately precise and accurate simulated sample size estimates, especially when there are many scenarios for the planning and/or the specified statistical method is complicated. In this article, we summarize the theoretical aspect of statistical simulation-based sample size calculation. Then, we propose a new simulation procedure for sample size calculation by fitting the probit model to simulation result data. From the theoretical and simulation-based evaluations, it is suggested that the proposed simulation procedure provide more efficient and accurate sample size estimates than ordinary algorithm-based simulation procedure especially when estimated sample sizes are moderate to large, therefore it would help to dramatically reduce the computational time required to conduct clinical trial simulations.

Network meta-analysis has been gaining prominence as an evidence synthesis method that enables the comprehensive synthesis and simultaneous comparison of multiple treatments. In many network meta-analyses, some of the constituent studies may have markedly different characteristics from the others, and may be influential enough to change the overall results. The inclusion of these "outlying" studies might lead to biases, yielding misleading results. In this article, we propose effective methods for detecting outlying and influential studies in a frequentist framework. In particular, we propose suitable influence measures for network meta-analysis models that involve missing outcomes and adjust the degree of freedoms appropriately. We propose three influential measures by a leave-one-trial-out cross-validation scheme: (1) comparison-specific studentized residual, (2) relative change measure for covariance matrix of the comparative effectiveness parameters, (3) relative change measure for heterogeneity covariance matrix. We also propose (4) a model-based approach using a likelihood ratio statistic by a mean-shifted outlier detection model. We illustrate the effectiveness of the proposed methods via applications to a network meta-analysis of antihypertensive drugs. Using the four proposed methods, we could detect three potential influential trials involving an obvious outlier that was retracted because of data falsifications. We also demonstrate that the overall results of comparative efficacy estimates and the ranking of drugs were altered by omitting these three influential studies.

In recent years, a concept of renal rehabilitation has become widely known among nephrology specialists, dialysis specialists, kidney transplantation specialists, rehabilitation specialists, nutrition specialists, guideline specialists, nurses, physiotherapists, and representatives of patients. Therefore, in order to make it clear the definition, methods, and effectiveness of renal rehabilitation in Japan, we launched Renal Rehabilitation Guideline Preparation Committee in 2016 as a part of works in the Japanese Society of Renal Rehabilitation, and created a guideline in accordance to the “Minds Handbook for Clinical Practice Guideline Development 2014”. Here, we report systematic reviews and recommendations of exercise therapies in patients with kidney diseases based on the guideline preparation committee works. Six recommendations for the condition of each kidney disorder, groups addressing nephritis/nephrosis, chronic kidney diseases, dialysis therapy, and kidney transplantation were created. All the recommendation grades were determined by a consensus conference participated in by representatives of patients and various professionals. The purpose of this report is to provide an evidence-based, best practice summary to optimize the quality, safety and efficacy, and availability of renal rehabilitation service, and to provide care for maximum patient prognosis, quality of life, and satisfaction.

The total score, which is calculated as the sum of scores in multiple items or questions, is repeatedly measured in longitudinal clinical studies. A mixed effects model for repeated measures method is often used to analyze these data; however, if one or more individual items are not measured, the method cannot be directly applied to the total score. We develop two simple and interpretable procedures that infer fixed effects for a longitudinal continuous composite variable. These procedures consider that the items that compose the total score are multivariate longitudinal continuous data and, simultaneously, handle subject-level and item-level missing data. One procedure is based on a multivariate marginalized random effects model with a multiple of Kronecker product covariance matrices for serial time dependence and correlation among items. The other procedure is based on a multiple imputation approach with a multivariate normal model. In terms of the type-1 error rate and the bias of treatment effect in total score, the marginalized random effects model and multiple imputation procedures performed better than the standard mixed effects model for repeated measures analysis with listwise deletion and single imputations for handling item-level missing data. In particular, the mixed effects model for repeated measures with listwise deletion resulted in substantial inflation of the type-1 error rate. The marginalized random effects model and multiple imputation methods provide for a more efficient analysis by fully utilizing the partially available data, compared to the mixed effects model for repeated measures method with listwise deletion.