Search

Abstract Inhibiting tubular urate reabsorption may protect the kidney from urate-induced tubular injury. However, this approach may promote intratubular uric acid crystallization, especially in acidified urine, which could be toxic to the kidney. To assess how tubular urate handling affects kidney outcomes, we conducted a retrospective cohort study including 1042 patients with estimated glomerular filtration rates (eGFR) of 15–60 mL/min/1.73 m2. The exposures were fractional excretion of uric acid (FEUA) and urinary uric acid-to-creatinine ratio (UUCR). The kidney outcome was defined as a halving of eGFR from baseline or initiating kidney replacement therapy. The median FEUA and UUCR were 7.2% and 0.33 g/gCre, respectively. During a median follow-up of 1.9 years, 314 kidney outcomes occurred. In a multivariate Cox model, the lowest FEUA quartile exhibited a 1.68-fold higher rate of kidney outcome than the highest FEUA quartile (95% confidence interval, 1.13–2.50; P = 0.01). Similarly, lower UUCR was associated with a higher rate of kidney outcome. Notably, patients in the highest quartile of FEUA and UUCR were at the lowest risk of kidney outcome even among those with aciduria. In conclusion, lower FEUA and UUCR were associated with a higher risk of kidney failure, suggesting that increased urate reabsorption is harmful to the kidney.

Abstract Background The HACOR score for predicting treatment failure includes vital signs and acid–base balance factors, whereas the ROX index only considers the respiratory rate, oxygen saturation, and fraction of inspired oxygen (FiO2). We aimed to externally validate the HACOR score and ROX index for predicting treatment failure in patients with coronavirus disease 2019 (COVID-19) on high-flow nasal cannula (HFNC) therapy in Japan. Methods This retrospective, observational, multicenter study included patients, aged ≥ 18 years, diagnosed with COVID-19 and treated with HFNC therapy between January 16, 2020, and March 31, 2022. The HACOR score and ROX index were calculated at 2, 6, 12, 24, and 48 h after stating HFNC therapy. The primary outcome was treatment failure (requirement for intubation or occurrence of death within 7 days). We calculated the area under the receiver operating characteristic curve (AUROC) and assessed the diagnostic performance of these indicators. The 2-h time-point prediction was considered the primary analysis and that of other time-points as the secondary analysis. We also assessed 2-h time-point sensitivity and specificity using previously reported cutoff values (HACOR score > 5, ROX index

Abstract Secondhand smoke (SHS) exposure causes various health problems associated with an unhealthy lifestyle. However, the lifestyles of individuals exposed to SHS have not been characterized extensively. Therefore, this cross-sectional study aimed to investigate the association between SHS exposure and lifestyle behaviors. The participants were 2379 healthy male employees at Osaka University who underwent health examinations. Physical and biochemical parameters and lifestyle behavior data were obtained from all the participants. Participants with SHS exposure had significantly higher body mass index, waist circumference, and serum levels of triglycerides and uric acid than that of those without SHS exposure. SHS exposure was significantly correlated with several lifestyle behaviors, including TV time, frequency of breakfast consumption and fried food consumption, vegetable and fruit intake, alcohol consumption frequency and daily alcohol intake, and smoking status. Thus, SHS exposure may be associated with an unhealthy lifestyle. The lifestyle behaviors of the smoke-excluded population were assessed further; however, SHS exposure was still associated with dietary and drinking habits. Since participants with SHS exposure are likely to have an unhealthy life and combined unhealthy lifestyle behaviors, the confounding effect of these factors should be considered when assessing the impact of SHS exposure on health.

Background and Objectives: Minimally invasive trauma management, including interventional radiology and non-operative approaches, has proven effective. Consequently, our hospital established a trauma IVR protocol called “Ohta Nishinouchi Hospital trauma protocol (ONH trauma protocol) in 2013, mainly for trunk trauma. However, the efficacy of the ONH trauma protocol has remained unverified. We aimed to assess the protocol’s impact using interrupted time-series analysis (ITSA). Materials and Methods: This retrospective cohort study was conducted at Ohta Nishinouchi hospital, a tertiary emergency hospital, from January 2004 to December 2019. We included patients aged ≥ 18 years who presented to our institution due to severe trauma characterized by an Abbreviated Injury Scale of ≥3 in any region. The primary outcome was the incidence of in-hospital deaths per 100 transported patients with trauma. Multivariable logistic regression analysis was conducted with in-hospital mortality as the outcome, with no exposure before protocol implementation and with exposure after protocol implementation. Results: Overall, 4558 patients were included in the analysis. The ITSA showed no significant change in in-hospital deaths after protocol induction (level change −1.49, 95% confidence interval (CI) −4.82 to 1.84, p = 0.39; trend change −0.044, 95% CI −0.22 to 0.14, p = 0.63). However, the logistic regression analysis revealed a reduced mortality effect following protocol induction (odds ratio: 0.50, 95% CI: 0.37 to 0.66, p < 0.01, average marginal effects: −3.2%, 95% CI: −4.5 to −2.0, p < 0.01). Conclusions: The ITSA showed no association between the protocol and mortality. However, before-and-after testing revealed a positive impact on mortality. A comprehensive analysis, including ITSA, is recommended over before-and-after comparisons to assess the impact of the protocol.

Smoking causes various health problems. Limited studies have reported a clinical effect of skipping breakfast on smoking initiation among adolescents. This retrospective cohort study aimed to assess the dose-dependent association between skipping breakfast and smoking initiation in university students. This study included 17,493 male and 8880 female students aged 18−22 years at a national university in Japan. The association between breakfast frequency (eating every day and skipping occasionally, often, and usually) and smoking initiation was evaluated using Cox proportional hazards models adjusted for clinically relevant factors. Smoking initiation was observed in 2027 (11.6%) male and 197 (2.2%) female students over the median observational period of 3.0 and 3.1 years. Skipping breakfast was significantly associated with smoking initiation in a dose-dependent fashion in male students (the adjusted hazard ratios [95% confidence interval] of eating breakfast every day and skipping occasionally, often, and usually: 1.00 [reference], 1.30 [1.15, 1.46], 1.47 [1.21, 1.79], and 1.77 [1.40, 2.25], respectively). Female students skipping breakfast occasionally and often were more vulnerable to smoking initiation than those who ate breakfast every day (1.00 [reference], 1.86 [1.24, 2.78], 2.97 [1.66, 5.32], and 1.76 [0.55, 5.64], respectively). Breakfast frequency may be useful to identify university students at risk of smoking initiation who need improvement in their health literacy.

A 66-year-old male was diagnosed with cT4N0M1b small-cell neuroendocrine carcinoma of the prostate. Four months after the administration of combined androgen blockade, multiple novel metastatic regions in the lung and liver and progression of bone metastasis were observed. The patient was referred to our hospital because of biochemical and radiographic progression after four cycles of docetaxel as a first-line therapy for castration-resistant prostate cancer. Transurethral resection of the prostate and hepatic biopsy revealed small-cell carcinoma with positive expression of neuroendocrine markers. The FoundationOne CDx next-generation sequencing test revealed several pathogenic variants, including BRCA2 (W1692fs*3), KEAP1 (R320W), and TP53 (C2385) mutation. After four cycles of chemotherapy with carboplatin plus etoposide (CE), the metastatic regions regressed markedly. The prostate-specific antigen (PSA) and neuron-specific enolase (NSE) level decreased by 96.9% and 91.6%, respectively. However, 2 months after the completion of four cycles of CE, elevation of tumor marker levels, and re-growth of the metastatic regions were observed. Although olaparib, a poly (ADP-ribose) polymerase inhibitor (PARPi), achieved a 45.2% decrease in NSE, the patient rejected to continue therapy because of G2 adverse events. After receiving an additional two cycles of CE and one cycle of cabazitaxel, the patient died because of cancer progression 24 months after the initial treatment for prostate cancer. Here, we present a case of BRCA2-altered small-cell neuroendocrine prostate cancer treated with both platinum-containing chemotherapy and PARPi. Both therapies achieved an initial response; however, durable responses were not obtained. Additional discussion regarding the optimal treatment strategy for BRCA-altered small-cell/neuroendocrine prostate cancer is required.

AbstractIn sports and rehabilitation settings, although haptic guidance is a general method for facilitating motor learning, the effects of verbal instruction on motor learning remain unclear when using haptic guidance. This study thus investigated the influence of verbal instruction on a novel visuo-motor task presented before practice, while also implementing haptic guidance. Thirty participants, who performed a mirror drawing task, were randomly allocated to three groups: control—without augmented verbal instruction, HG-with relying (HG-with)—instructed to rely on guidance devices, and HG-without relying (HG-without)—instructed not to rely on guidance devices. We assessed the tracing time and error area of the mirror drawing task as performance measurements. The self-made guidance devices used in the practice session were constructed of 2-mm-thick cardboard and had a 5-mm-wide groove that matched the shape of the target figure. The tracing time in HG-with condition during the practice session (median = 66.5 s, IQR = 55.3–80.5 s) was significantly shorter compared with that in control condition (median = 132.5 s, IQR = 125.0–144.8 s) (p = .019). The error area (median = 585.0 mm2, IQR = 559–687.0 mm2) was also significantly larger in the HG-with condition than in control condition (median = 413.5 mm2, IQR = 350.5–494.0 mm2) (p = .029). Additionally, HG-with condition (mean = 46 %, SD = 12.3 %) showed greater improvement rate for tracing time from pre-test to post-test than HG-without condition (mean = 30 %, SD = 8.3 %) (p = .032). Our results suggest that, even if the same haptic guidance was implemented, visuo-motor task improvement was influenced by verbal instructions.

Abstract Fibroblast growth factor 23, parathyroid hormone, and 1,25-dihydroxyvitamin D are critical in phosphate homeostasis. Despite these factors’ importance, regulators of phosphaturia in the acute postprandial phase remain largely unknown. This study investigated the mechanism of acute phosphate regulation in the postprandial phase in rats. Duodenal administration of radiolabeled phosphate (32P) showed that 32P levels in the inferior vena cava (IVC) blood were lower than those in the portal vein (PV) blood. Serum phosphate concentration transiently increased 5 min after phosphate solution administration through IVC, while it was maintained after the administration through PV. Phosphate administration through both IVC and PV resulted in increased fractional excretion of phosphate (FEPi) at 10 min without elevation of the known circulating factors, but urinary phosphate excretion during the period was 8% of the dose. Experiments using 32P or partial hepatectomy showed that the liver was one of the phosphate reservoirs. The elevation of FEPi and suppression of sodium-phosphate cotransporter 2a in the kidney at 10 min was attenuated in rats with SCH23390, hepatic denervation, or renal denervation, thus indicating that the liver communicated with the kidney via the nervous system to promote phosphaturia. These results revealed previously unknown mechanisms for serum phosphate maintenance.

Abstract We sought to verify the reliability of machine learning (ML) in developing diabetes prediction models by utilizing big data. To this end, we compared the reliability of gradient boosting decision tree (GBDT) and logistic regression (LR) models using data obtained from the Kokuho-database of the Osaka prefecture, Japan. To develop the models, we focused on 16 predictors from health checkup data from April 2013 to December 2014. A total of 277,651 eligible participants were studied. The prediction models were developed using a light gradient boosting machine (LightGBM), which is an effective GBDT implementation algorithm, and LR. Their reliabilities were measured based on expected calibration error (ECE), negative log-likelihood (Logloss), and reliability diagrams. Similarly, their classification accuracies were measured in the area under the curve (AUC). We further analyzed their reliabilities while changing the sample size for training. Among the 277,651 participants, 15,900 (7978 males and 7922 females) were newly diagnosed with diabetes within 3 years. LightGBM (LR) achieved an ECE of 0.0018 ± 0.00033 (0.0048 ± 0.00058), a Logloss of 0.167 ± 0.00062 (0.172 ± 0.00090), and an AUC of 0.844 ± 0.0025 (0.826 ± 0.0035). From sample size analysis, the reliability of LightGBM became higher than LR when the sample size increased more than $$10^4$$ 10 4 . Thus, we confirmed that GBDT provides a more reliable model than that of LR in the development of diabetes prediction models using big data. ML could potentially produce a highly reliable diabetes prediction model, a helpful tool for improving lifestyle and preventing diabetes.

Background: It is crucial to understand the seasonal variation of Metabolic Syndrome (MetS) for the detection and management of MetS. Previous studies have demonstrated the seasonal variations in MetS prevalence and its markers, but their methods are not robust. To clarify the concrete seasonal variations in the MetS prevalence and its markers, we utilized a powerful method called Seasonal Trend Decomposition Procedure based on LOESS (STL) and a big dataset of health checkups. Methods: A total of 1,819,214 records of health checkups (759,839 records for men and 1,059,375 records for women) between April 2012 and December 2017 were included in this study. We examined the seasonal variations in the MetS prevalence and its markers using 5 years and 9 months health checkup data and STL analysis. MetS markers consisted of waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure (DBP), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), fasting plasma glucose (FPG). Results: We found that the MetS prevalence was high in winter and somewhat high in August. Among men, MetS prevalence was 2.64 ± 0.42 (mean ± SD) % higher in the highest month (January) than in the lowest month (June). Among women, MetS prevalence was 0.53 ± 0.24% higher in the highest month (January) than in the lowest month (June). Additionally, SBP, DBP, and HDL-C exhibited simple variations, being higher in winter and lower in summer, while WC, TG, and FPG displayed more complex variations. Conclusions: This finding, complex seasonal variations of MetS prevalence, WC, TG, and FPG, could not be derived from previous studies using just the mean values in spring, summer, autumn and winter or the cosinor analysis. More attention should be paid to factors affecting seasonal variations of central obesity, dyslipidemia and insulin resistance.

Abstract In this study, we investigated the differences of the effectiveness from concurrent visual feedback among younger and older adults in learning tasks that require adjustability of grasping force (AGF), as well as the functions related to AGF in each generation. The younger and older adult groups were evaluated for simple visual reaction time as visual-motor speed (VMS) and a 100 g AGF task that reflected the difference between desired performance and actual performance. The main learning task was then practiced using concurrent visual feedback and tested without feedback. The VMS of older adults was slower than that of the younger, and the error in the 100 g AGF task was larger in older adults than in the younger adults. Performance improved from pre-test to retention test in both groups, but the older adult group failed to reach the level of the younger adult group. The results of this study show that concurrent visual feedback is effective for learning the tasks that require AGF in both groups. Indicatively, improvement in performance during practice is insufficient in older people for whom there is a large difference between desired performance and actual performance, or whose VMS is slow.

Abstract The effects of lower tidal volume ventilation (LTV) were controversial for patients with acute respiratory distress syndrome (ARDS). This systematic review and meta-analysis aimed to evaluate the use of LTV strategy in patients with ARDS. We performed a literature search on MEDLINE, CENTRAL, EMBASE, CINAHL, “Igaku-Chuo-Zasshi”, clinical trial registration sites, and the reference of recent guidelines. We included randomized controlled trials (RCTs) to compare the LTV strategy with the higher tidal volume ventilation (HTV) strategy in patients with ARDS. Two authors independently evaluated the eligibility of studies and extracted the data. The primary outcomes were 28-day mortality. We used the GRADE methodology to assess the certainty of evidence. Among the 19,864 records screened, 13 RCTs that recruited 1874 patients were included in our meta-analysis. When comparing LTV (4–8 ml/kg) versus HTV (> 8 ml/kg), the pooled risk ratio for 28-day mortality was 0.79 (11 studies, 95% confidence interval [CI] 0.66–0.94, I2 = 43%, n = 1795, moderate certainty of evidence). Subgroup-analysis by combined high positive end-expiratory pressure with LTV showed interaction (P = 0.01). Our study indicated that ventilation with LTV was associated with reduced risk of mortality in patients with ARDS when compared with HTV. Trial registration: UMIN-CTR (UMIN000041071).

Abstract Previous studies reported conflicting results regarding an association between serum albumin concentration and the cumulative incidence of remission of proteinuria in adult patients with minimal change disease (MCD). The present study aimed to clarify the clinical impact of serum albumin concentration and the cumulative incidence of remission and relapse of proteinuria in 108 adult patients with MCD at 40 hospitals in Japan, who were enrolled in a 5-year prospective cohort study of primary nephrotic syndrome, the Japan Nephrotic Syndrome Cohort Study (JNSCS). The association between serum albumin concentration before initiation of immunosuppressive treatment (IST) and the cumulative incidence of remission and relapse were assessed using multivariable-adjusted Cox proportional hazards models. Remission defined as urinary protein 1.5 g/dL) showed significantly slow remission. In conclusion, lower serum albumin concentration and higher eGFR were associated with earlier remission in MCD, but not with relapse.

Abstract Introduction Warm ischemia time (WIT) is a primary concern for robot-assisted laparoscopic partial nephrectomy (RALPN) patients because longer WIT is significantly associated with postoperative deteriorating kidney function. Tumor complexity, determined by the RENAL nephrometry score (RENAL score), can help predict surgical outcomes, but it is unclear what RENAL score and clinical factors affect WIT. This study explored the clinical factors predicting long WIT in experienced surgeon to RALPN. Materials and methods In our institute, 174 RALPNs were performed between November 2013 and February 2021, of which 114 were performed by a single surgeon and included in this study. Clinical staging and the total RENAL score were determined based on preoperative CT scans. The cases were divided into three groups based on experience: period 1: 1–38, period 2: 39–76, and period 3: 77–114. The clinical factors associated with longer WIT were analyzed per period. Results The overall median tumor diameter was 32 mm, and one patient had a positive surgical margin, but there were no cancer-related deaths. In total, there were 18 complications (15.8%). Periods 2 and 3 had larger tumor diameters (p < 0.01) and worse preoperative kidney function (p = 0.029) than period 1. A RENAL L-component score of 3 was associated with longer WIT in period 3 (odds ratio: 3.900; 95% confidence interval: 1.004–15.276; p = 0.044), but the tumor diameter and the total RENAL score were not. Conclusions A large tumor in the central lesion indicated by the RENAL L-component score was associated with increased WIT in RALPN.

Abstract Background Post-extubation dysphagia (PED) is recognized as a common complication in the intensive care unit (ICU). Speech and language therapy (SLT) can potentially help improve PED; however, the impact of the timing of SLT initiation on persistent PED has not been well investigated. This study aimed to examine the timing of SLT initiation and its effect on patient outcomes after extubation in the ICU. Methods We conducted this multicenter, retrospective, cohort study, collecting data from eight ICUs in Japan. Patients aged ≥ 20 years with orotracheal intubation and mechanical ventilation for longer than 48 h, and those who received SLT due to PED, defined as patients with modified water swallowing test scores of 3 or lower, were included. The primary outcome was dysphagia at hospital discharge, defined as functional oral intake scale score

Abstract Background Phlebitis is an important complication occurring in patients with peripheral intravascular catheters (PIVCs). The risk factors for phlebitis in the intensive care unit (ICU) was examined. Methods A secondary analysis of a prospective multicenter cohort study was conducted, involving 23 ICUs in Japan—the AMOR–VENUS study. Consecutive patients aged ≥ 18 years admitted to the ICU with newly inserted PIVCs after ICU admission were enrolled. Characteristics of the ICU, patients, PIVCs, and the drugs administered via PIVCs were recorded. A marginal Cox regression model was used to identify the risk factors associated with phlebitis. Results A total of 2741 consecutive patients from 23 ICUs were reviewed for eligibility, resulting in 1359 patients and 3429 PIVCs being included in the analysis population. The median dwell time was 46.2 h (95% confidence interval [CI], 21.3–82.9). Phlebitis occurred in 9.1% (95% CI, 8.2–10.1%) of catheters (3.5 cases/100 catheter days). The multivariate analysis revealed that the only factors that increased the risk of developing phlebitis were drugs administered intravenously. This study included 26 drugs, and 4 were associated with increased phlebitis: nicardipine (HR, 1.85; 95% CI, 1.29–2.66), noradrenaline (HR, 2.42; 95% CI, 1.40–4.20), amiodarone (HR, 3.67; 95% CI, 1.75–7.71) and levetiracetam (HR, 5.65; 95% CI, 2.80–11.4). Alternatively, factors significantly associated with a reduced risk of phlebitis were: standardized drug administration measures in the ICU (HR, 0.35; 95% CI, 0.17–0.76), 30≤ BMI (HR, 0.43; 95% CI, 0.20–0.95), catheter inserted by a doctor as nurse reference (HR, 0.55; 95% CI, 0.32–0.94), and upper arm insertion site as forearm reference (HR, 0.52; 95% CI, 0.32–0.85). The nitroglycerin was associated with a reduced phlebitis risk (HR, 0.22; 95% CI, 0.05–0.92). Conclusion Various factors are involved in the development of phlebitis caused by PIVCs in critically ill patients, including institutional, patient, catheter, and drug-induced factors, indicating the need for appropriate device selection or models of care in the ICU. Trial registration: UMIN-CTR, the Japanese clinical trial registry (registration number: UMIN000028019, July 1, 2017).

Abstract Aim Multicenter collaborative research accelerates patient recruitment and strengthens evidence. Nevertheless, the factors influencing emergency and critical care physicians’ involvement in such research in Japan remain unclear. Methods A nationwide web‐based survey conducted in early 2023 targeted emergency physicians working a minimum of 3 days per week in Japan. The survey descriptively assessed their backgrounds, work and research environments, experiences, and perceived impediments and motivators for multicenter research. Results Of the 387 respondents, 348 were included in the study, yielding a 5.1% response rate. Women comprised 11% of the participants; 33% worked in university hospitals, 65% served in both emergency departments and intensive care units, and 54% did shift work. Only 12% had designated research time during working hours, with a median of 1 hour per week (interquartile range 0–5 h), including time outside of work. While 73% had participated in multicenter research, 58% noted barriers to participation. The key obstacles were excessive data entry (72%), meeting time constraints (59%), ethical review at each facility (50%), and unique sample collection, such as bronchoalveolar lavage specimens or pathological tissues (51%). The major incentives were networking (70%), data sets reuse (65%), feedback on research results (63%), and recognition from academic societies (63%). Financial rewards were not highly prioritized (38%). Conclusions While valuing clinical research, emergency physicians face barriers, especially data entry burden and limited research time. Networking and sharing research findings motivate them. These insights can guide strategies to enhance collaborative research in emergency and critical care in Japan.

BackgroundPrevious studies have shown that diarrhea, defined as a dichotomized cutoff, is associated with increased mortality of patients in intensive care units (ICUs). This study aimed to examine the dose-response relationship between the quantity of diarrhea and mortality in ICU patients with newly developed diarrhea.MethodsWe conducted this single-center retrospective cohort study. We consecutively included all adult patients with newly developed diarrhea in the ICU between January 2017 and December 2018. Newly developed diarrhea was defined according to the World Health Organization definition. The consistency of diarrhea was evaluated by the Bristol stool chart scale, and the quantity of diarrhea was assessed on the day when patients newly developed diarrhea. The primary outcome was in-hospital mortality. The risk ratio (RR) and 95% confidence interval (CI) for the association between diarrhea quantity and mortality were estimated using multivariable modified Poisson regression models.ResultsAmong the 231 participants, 68.4% were men; the median age was 72 years. The median diarrhea quantity was 401g (interquartile range [IQR] 230‒645g), and in-hospital mortality was 22.9%. More diarrhea at baseline was associated with higher in-hospital mortality; the adjusted RR (95% CI) per 200-g increase was 1.10 (1.01‒1.20), p = 0.029. In sensitivity analyses with near quartile categories of diarrhea quantity (ConclusionsA greater quantity of diarrhea was an independent risk factor for in-hospital mortality. The diarrhea quantity may be an indicator of disease severity in ICU patients.

Introduction: Knowledge of results (KR) is a method of augmented feedback where frequency or timing varies depending on the individual’s performance. In previous studies, bandwidth (BW) KR was not established according to the individual’s performance; thus, it is unclear how BW should be set based on changes in individual performance. Therefore, this study investigated the effectiveness of adjusted BW KR. Method: Forty-seven participants were divided into four groups (control, narrow BW, wide BW, and adjusted BW). The adjustability of the grasping force task was measured by having participants perform the task for 60 seconds, with each group receiving a different KR. We used the absolute constant error (ACE) and variable error (VE) as respective measures of the accuracy and consistency of the movements, and the sum of ACEs outside of the BW as a measure of the amount of error information. Measurements (pretest, practice sessions, and immediate- and delayed-retention tests) were performed over the course of two days. Results: The adjusted BW group showed a significant decrease in VE compared with the wide BW group in the immediate-retention test. Conclusion: This study partially indicates the effectiveness of adjusted BW KR compared to traditional BW KR.

Abstract Radiation therapy is one of standard treatment for malignant glioma after surgery. The microenvironment after irradiation is considered not to be suitable for the survival of tumor cells (tumor bed effect). This study investigated whether the effect of changes in the microenvironment of parenchymal brain tissue caused by radiotherapy affect the recurrence and progression of glioma. 65-Gy irradiation had been applied to the right hemisphere of Fisher rats. After 3 months from irradiation, we extracted RNA and protein from the irradiated rat brain. To study effects of proteins extracted from the brains, we performed WST-8 assay and tube formation assay in vitro. Cytokine production were investigated for qPCR. Additionally, we transplanted glioma cell into the irradiated and sham animals and the median survival time of F98 transplanted rats was also examined in vivo. Immunohistochemical analyses and invasiveness of implanted tumor were evaluated. X-ray irradiation promoted the secretion of cytokines such as CXCL12, VEGF-A, TGF-β1 and TNFα from the irradiated brain. Proteins extracted from the irradiated brain promoted the proliferation and angiogenic activity of F98 glioma cells. Glioma cells implanted in the irradiated brains showed significantly high proliferation, angiogenesis and invasive ability, and the post-irradiation F98 tumor-implanted rats showed a shorter median survival time compared to the Sham-irradiation group. The current study suggests that the microenvironment around the brain tissue in the chronic phase after exposure to X-ray radiation becomes suitable for glioma cell growth and invasion.

Abstract Fibroblast growth factor (FGF) 21 has various functions, including glucose and lipid metabolism. This cross-sectional study aimed to investigate specific conditions that might influence the functions of FGF21. 398 men who underwent a health examination were enrolled in this study. Physical and biochemical parameters and information on several lifestyle behaviors were obtained from all subjects. FGF21 levels correlated with age, body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure (DBP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (γ-GTP), uric acid, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDLC), fasting plasma glucose (FPG), and HbA1c. Moreover, FGF21 levels were significantly associated with lifestyle behaviors, including smoking status and breakfast and alcohol consumption frequency. Multivariable regression analysis showed that age, ALT, γ-GTP, smoking status, and breakfast and alcohol consumption frequency were independent variables for FGF21 levels. Assessment among the non-obese and obese groups showed that FGF21 levels correlated with WC, SBP, and TC only in the non-obese group. Thus, serum FGF21 levels were affected by several factors, including lifestyle behaviors, age, and liver function. To assess the functions of FGF21 in individuals, considering these factors would be essential.

Abstract No study has assessed the association between no health checkup and end-stage kidney disease (ESKD). This retrospective cohort study, including 69,147 adults aged ≥ 40 years in Japan who were insured by the National Health Insurance and the Late-Stage Medical Care System for the Elderly, assessed the associations of kidney tests at medical facilities and health checkups with incident ESKD. The main exposure was the histories of kidney tests using dipstick urinalysis and/or serum creatinine measurement at medical facilities and checkups in the past year: “checkups,” “no kidney test (without checkup),” and “kidney tests (without checkup)” groups. During the median observational period of 5.0 years, ESKD was observed in 246 (0.8%) men and 124 (0.3%) women. The “no kidney test” group was associated with ESKD in men (adjusted subhazard ratio of “no kidney test” vs. “checkups”: 1.66 [95% confidence interval, 1.04–2.65], but not in women. Age-specific subgroup analyses identified the “no kidney test” group as a high-risk population of ESKD in elderly men (1.30 [0.70–2.41] and 2.72 [1.39–5.33] in men aged 40–74 and ≥ 75 years, respectively). Elderly men with no kidney test at medical facilities and no health checkup were at higher risk of ESKD.

Increased expression of angiotensin-converting enzyme 2 (ACE2) is one of the likely explanations for disease severity in patients with coronavirus disease 2019 (COVID-19). In this study, we aimed to test whether soluble ACE2 (sACE2) levels are correlated to known risk factors of severe COVID-19 including biochemical parameters, body mass index and smoking habits. We cross-sectionally evaluated serum sACE2 levels in obese or tobacco-smoking populations and compared them to those in non-obese and non-smoking healthy participants. Additionally, fibroblast growth factor-21 (FGF21) was investigated as a candidate regulator of sACE2. A total of 220 male participants aged 30–59 years undergoing an annual health checkup were enrolled in this study: 59 obese, 80 smokers, and 81 healthy. Serum sACE2 levels were significantly higher in obese participants but not in tobacco-smoking participants when compared to healthy participants. sACE2 levels were significantly correlated with total cholesterol and triglycerides but not with body mass index. Furthermore, no regulatory relationship was found between FGF21 and sACE2. Lipid metabolism disorders accompanied by upregulation of serum sACE2 may be underlying mechanisms of COVID-19 aggravation and might be a novel breakthrough treatment target.

This retrospective cohort study investigates the association between the incidence of sleep problems and changes in digital media use among university students during the COVID-19 pandemic. It used data from annual health check-ups performed at a Japanese university in 2019 and 2020. Students undergoing these check-ups were identified to respond to questions about sleep problems, digital media use, breakfast and exercise habits, and stress. In total, 3,869 students were included in the analysis. The association between the incidence of sleep problems in 2020 and the changes in digital media use between 2019 and 2020 was assessed using logistic regression models. The rate of long digital media use (≥ 2 hours) in 2019 was 42.6%, while in 2020 it was 53.6%. Incidence of sleep problems was observed in 244 students (6.3%) in 2020. There were 786 students (20.3%) who used digital media for ≤ 2 h in 2019 and ≥ 2 h in 2020. From the sample, 66 students (8.4%) reported incidence of sleep problems in 2020. Additionally, those respondents who specifically reported increased digital media use between 2019 and 2020 (increased use) where at greater risk (OR: 1.76; 95% CI: 1.21, 2.55) of reporting sleep problems in 2020, even after controlling for other study variables. Thus, this study provides evidence that the incidence of sleep problems has had a significant association with an increase in digital media use among university students throughout the COVID-19 pandemic. These findings highlight the importance of ensuring appropriate digital media use among students for improved quality of sleep.

Abstract Angiotensin‐converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are prescribed as conservative or adjunctive therapies for adult idiopathic nephrotic syndrome. However, studies on real‐world practice patterns are scarce. This study aimed to examine the prevalence and incidence of ACEI/ARB prescription and their associated factors. This nationwide cohort study included adult Japanese patients with idiopathic nephrotic syndrome including minimal change disease (MCD), membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS), and others. The outcomes were the prevalence of ACEI/ARB prescription at baseline (date of renal biopsy or date of immunosuppressant initiation) and at 2 months after baseline. Of the 326 eligible patients, 122 (37.4%) had already been prescribed ACEIs/ARBs. Of the remaining 204 patients, 67 (32.7%) were newly prescribed within the 2‐month period. MN/FSGS (vs. MCD, adjusted odds ratio [AOR]: 4.96 [95% confidence interval {CI} 2.53–9.72] and 3.95 [95% CI 1.61–9.66], respectively), higher age (per 1‐yr increase, AOR: 1.02 [95% CI 1.00–1.04]), other hypertensive agents (AOR: 2.18 [95% CI 1.21–3.92]), antidiabetic drug (AOR: 6.57 [95% CI 1.77–24.4]) were associated with a higher prevalence of ACEI/ARB prescription. MN (vs. MCD, AOR: 6.00 [95% CI 2.57–14.0]) and higher baseline systolic blood pressure (SBP) (per 10‐mmHg increase, AOR: 1.36 [95% CI 1.09–1.70]) were associated with a higher incidence of ACEI/ARB prescription. On average, incidence of ACEI/ARB prescription increased from 19.2% to 40.8% as baseline SBP increased from 100 to 140 mmHg. Thus, Japanese nephrologists are likely to prescribe ACEIs/ARBs for nephrotic patients with MN or high baseline SBP, even below the hypertensive range.

Previous cohort studies have reported conflicting associations between alcohol consumption and chronic kidney disease, characterized by proteinuria and low glomerular filtration rate (GFR). This systematic review, which included 14,634,940 participants from 11 cohort studies, assessed a dose-dependent association of alcohol consumption and incidence of proteinuria and low estimated GFR (eGFR) of 2. Compared with non-drinkers, the incidence of proteinuria was lower in drinkers with alcohol consumption of ≤12.0 g/day (relative risk 0.87 [95% confidence interval 0.83, 0.92]), but higher in drinkers with alcohol consumption of 36.1–60.0 g/day (1.09 [1.03, 1.15]), suggesting a J-shaped association between alcohol consumption and the incidence of proteinuria. Incidence of low eGFR was lower in drinkers with alcohol consumption of ≤12.0 and 12.1–36.0 than in non-drinkers (≤12.0, 12.1–36.0, and 36.1–60.0 g/day: 0.93 [0.90, 0.95], 0.82 [0.78, 0.86], and 0.89 [0.77, 1.03], respectively), suggesting that drinkers were at lower risk of low eGFR. In conclusion, compared with non-drinkers, mild drinkers were at lower risk of proteinuria and low eGFR, whereas heavy drinkers had a higher risk of proteinuria but a lower risk of low eGFR. The clinical impact of high alcohol consumption should be assessed in well-designed studies.

Previous studies have reported conflicting results on the clinical impact of alcohol consumption on the glomerular filtration rate (GFR). This retrospective cohort study aimed to assess the dose-dependent association between alcohol consumption and the slope of the estimated GFR (eGFR) in 304,929 participants aged 40–74 years who underwent annual health checkups in Japan between April 2008 and March 2011. The association between the baseline alcohol consumption and eGFR slope during the median observational period of 1.9 years was assessed using linear mixed-effects models with the random intercept and random slope of time adjusting for clinically relevant factors. In men, rare drinkers and daily drinkers with alcohol consumptions of ≥60 g/day had a significantly larger decline in eGFR than occasional drinkers (difference in multivariable-adjusted eGFR slope with 95% confidence interval (mL/min/1.73 m2/year) of rare, occasional, and daily drinkers with ≤19, 20–39, 40–59, and ≥60 g/day: −0.33 [−0.57, −0.09], 0.00 [reference], −0.06 [−0.39, 0.26], −0.16 [−0.43, 0.12], −0.08 [−0.47, 0.30], and −0.79 [−1.40, −0.17], respectively). In women, only rare drinkers were associated with lower eGFR slopes than occasional drinkers. In conclusion, alcohol consumption was associated with the eGFR slope in an inverse U-shaped fashion in men but not in women.

Abstract Background The lack of precise information on the epidemiology of peripheral intravascular catheter (PIVC)-related phlebitis and complications in critically ill patients results in the absence of appropriate preventive measures. Therefore, we aimed to describe the epidemiology of the use of PIVCs and the incidence/occurrence of phlebitis and complications in the intensive care unit (ICU). Methods This prospective multicenter cohort study was conducted in 23 ICUs in Japan. All consecutive patients aged ≥ 18 years admitted to the ICU were enrolled. PIVCs inserted prior to ICU admission and those newly inserted after ICU admission were included in the analysis. Characteristics of the ICU, patients, and PIVCs were recorded. The primary and secondary outcomes were the occurrence and incidence rate of PIVC-related phlebitis and complications (catheter-related blood stream infection [CRBSI] and catheter failure) during the ICU stay. Results We included 2741 patients and 7118 PIVCs, of which 48.2% were inserted in the ICU. PIVC-related phlebitis occurred in 7.5% (95% confidence interval [CI] 6.9–8.2%) of catheters (3.3 cases / 100 catheter-days) and 12.9% (95% CI 11.7–14.2%) of patients (6.3 cases / 100 catheter-days). Most PIVCs were removed immediately after diagnosis of phlebitis (71.9%). Grade 1 was the most common phlebitis (72.6%), while grade 4 was the least common (1.5%). The incidence rate of CRBSI was 0.8% (95% CI 0.4–1.2%). In cases of catheter failure, the proportion and incidence rate per 100 intravenous catheter-days of catheter failure were 21% (95% CI 20.0-21.9%) and 9.1 (95% CI 8.7–10.0), respectively. Conclusion PIVC-related phlebitis and complications were common in critically ill patients. The results suggest the importance of preventing PIVC-related complications, even in critically ill patients. Trial registration UMIN-CTR, the Japanese clinical trial registry (registration number: UMIN000028019 , July 1, 2017).

Abstract Heart failure is a major cause of death with an increasing population of elderly individuals. Several studies have demonstrated the involvement of soluble alpha-Klotho (sαKl) in various diseases. However, the correlation between sαKl and heart failure remains to be understood. The aim of this study is to investigate the levels and role of sαKl in patients with heart failure. Twenty-eight consecutive patients with acute heart failure (19 male, 9 female), admitted to the Osaka University Hospital from 2010 to 2018, were enrolled in this study. Mean NYHA score, left ventricular ejection fraction and BNP were 3.3, 17.0% and 588 pg/mL, respectively. SαKl significantly increased in heart failure patients. SαKl on admission were significantly higher in patients with heart failure who showed improvement after intensive treatment than that in patients who did not show improvement after the treatment. SαKl levels decreased significantly in patients who showed improvement. Interestingly, sαKl levels increased in male patients with heart failure, but not in female patients. Our data suggest that soluble αKl may be a novel biomarker for the responsiveness against treatment in patients with heart failure with reduced ejection fraction. Our findings may help developing a personalized therapy for different patients with heart failure.

BackgroundCoronavirus disease 2019 (COVID-19) patients reportedly have high bicarbonate concentration. However, its relationship to the disease progression are obscure.MethodsIn this two-center retrospective study, we included COVID-19 patients with moderate severity between March 2020 and May 2021. We classified patients into three groups according to bicarbonate concentrations: high (>27 mEq/L), normal (21 to 27 mEq/L), and low (ResultsOf the 60 participants (median age 72 years), 60% were men. Participants were classified into high (13 patients), normal (30 patients), and low (17 patients) groups. Clinical worsening occurred in 54% of patients in the high group, 23% in the normal group, and 65% in the low group. Both high and low groups were associated with a higher clinical worsening rate: HR, 3.02 (95% CI, 1.05 to 8.63) in the high group; 3.49 (95% CI: 1.33 to 9.12) in the low group.ConclusionMonitoring of bicarbonate concentrations may be useful to predict the prognosis.

The purpose of this study was to evaluate the effects of NR1I2 (7635G>A and 8055C>T) and ABCB1 (1236C>T, 2677G>T/A, and 3435C>T) genetic polymorphisms on everolimus pharmacokinetics in 98 Japanese renal transplant patients. On day 15 after everolimus administration, blood samples were collected just prior to and 1, 2, 3, 4, 6, 9, and 12 h after administration. The dose-adjusted area under the blood concentration–time curve (AUC0-12) of everolimus was significantly lower in patients with the NR1I2 8055C/C genotype than in those with other genotypes (p = 0.022) and was significantly higher in male patients than female patients (p = 0.045). Significant correlations between the dose-adjusted AUC0-12 of everolimus and age (p = 0.001), aspartate transaminase (p = 0.001), and alanine transaminase (p = 0.005) were found. In multivariate analysis, aging (p = 0.008) and higher alanine transaminase levels (p = 0.032) were independently predictive of a higher dose-adjusted everolimus AUC0-12. Aging and hepatic dysfunction in patients may need to be considered when evaluating dose reductions in everolimus. In renal transplant patients, management using everolimus blood concentrations after administration may be more important than analysis of NR1I2 8055C>T polymorphism before administration.

Abstract Purpose To examine the association of a simple frailty assessment, Life Space (LS), with in-hospital mortality in elderly patients with sepsis. Methods We used data from a single hospital between 2014 and 2017. We included elderly patients (age ≥ 65 years) admitted to the intensive care unit (ICU) with sepsis, as defined by sepsis-3 criteria. Frailty assessment was based on a patient’s ability to independently go out of the house before the ICU admission. We termed this dichotomous score as Life Space. The primary outcome was in-hospital mortality. Logistic regression was used to investigate the association of LS with each outcome after adjusting for age, sex, and Sequential Organ Failure Assessment score. Results Of the 335 participants included in the final analysis, 121 (36%) were classified as frail. LS-positive patients had a higher in-hospital mortality (adjusted odds ratio (aOR) 2.32; 95% confidence interval (CI) 1.36–3.96; P = 0.002) than did LS-negative patients. We observed similar patterns in six sets of sensitivity analyses after accounting for different confounders. In subgroup analyses, significant interactions were observed in participants with versus those without treatment limitations (aOR 1.02 vs. 2.66, P for interaction = 0.042). Conclusions In this single-center study, frailty assessed by LS was independently associated with a higher in-hospital mortality.

Cytoplasmic genomes affect various phenotypes, including abiotic stress responses, through interaction with nuclear genomes in plants. We focused on the effects of cytoplasmic substitution on germination and seedling growth in combinations with submergence and seed ageing, both of which are known to inhibit these traits posing a challenge in agriculture and seed banking. We carried out comparative phenotypic studies of submergence and seed ageing effects using a series of nucleus–cytoplasm (NC) hybrids of wheat, in which 11 heterologous cytoplasms of Triticum and Aegilops species were combined with a common nucleus. Adopting the test-tube bioassay, germination and seedling growth were studied using aged and non-aged seeds. Imbibed seeds were subjected to 3-days submergence followed by incubation under de-submergence conditions. Seed ageing reduced the germination rates in NC hybrids. Submergence and seed ageing both caused reduction of seedling growth evaluated by shoot length in all or most of the lines. The magnitude of shoot growth inhibition by submergence and seed ageing varied greatly among NC hybrids compared with the nuclear donor, and three distinct response types were recognized. Submergence and seed ageing, in combination, caused leaf chlorosis in most of NC hybrids. Our results suggested that the observed diverse effects of cytoplasmic substitution were exerted through differential interactions with submergence and seed ageing. Further studies are needed to clarify the mechanisms underlying cytoplasmic genome diversity and interaction with nuclear genomes affecting submergence and seed ageing responses in wheat.

Abstract Background A bronchopleural fistula (BPF) can lead to empyema and death after pulmonary resection. A minor leakage from a BPF has been reported to be successfully closed endobronchially, although thoracoplasty is usually needed. Case presentation A case of successful thoracoscopic BPF closure using an omental flap in a 74-year-old man with emphysema who developed a BPF after right lower lobectomy for lung cancer is reported. Reoperation was performed to close the BPF using an omental flap. After successful closure of the BPF, the empyema resolved with intravenous antibiotics. Conclusions Thoracoscopic single-stage omentoplasty without thoracotomy might be a useful treatment method when a BPF is diagnosed early.

Frequency of alcohol drinking is a potential predictor of binge drinking of alcohol, a serious social problem for university students. Although previous studies have identified skipping breakfast as a predictor of various health-compromising behaviors and cardiometabolic diseases, few studies have assessed the association between skipping breakfast and the incidence of frequent alcohol drinking. This retrospective cohort study included 17,380 male and 8799 female university students aged 18–22 years admitted to Osaka universities between 2004 and 2015. The association between breakfast frequency (eating every day, skipping occasionally, and skipping often/usually) and the incidence of frequent alcohol drinking, defined as drinking ≥4 days/week, was assessed using multivariable-adjusted Cox proportional hazards models. During the median observational period of 3.0 years, 878 (5.1%) men and 190 (2.2%) women engaged in frequent alcohol drinking. Skipping breakfast was significantly associated with the incidence of frequent alcohol drinking (adjusted hazard ratios [95% confidence interval] of eating every day, skipping occasionally, and skipping often/usually: 1.00 [reference], 1.02 [0.84–1.25], and 1.48 [1.17–1.88] in men; 1.00 [reference], 1.60 [1.03–2.49], and 3.14 [1.88–5.24] in women, respectively). University students who skipped breakfast were at a higher risk of frequent alcohol drinking than those who ate breakfast every day.

The reclassification of membranoproliferative glomerulonephritis (MPGN) into immune-complex MPGN (IC-MPGN) and C3 glomerulopathy (C3G) based on immunofluorescence findings in kidney biopsies has provided insights into these two distinct diseases. C3G is further classified into dense deposit disease and C3 glomerulonephritis (C3GN) based on electron micrographic findings. Although these diseases have poor outcomes, limited Japanese literature confined to small, single-center cohorts exist on these diseases. We retrospectively analyzed 81 patients with MPGN type I and III from 15 hospitals in the Japan Renal Biopsy Registry to compare demographic, clinical characteristics and treatment outcomes of patients with IC-MPGN to those with C3GN. Of the 81 patients reviewed by immunofluorescence findings in kidney biopsies, 67 patients had IC-MPGN and 14 patients had C3GN. Age at diagnosis and systolic and diastolic pressure were higher and proteinuria and impaired renal function were significantly more prevalent in patients with IC-MPGN than those with C3GN. About 80% of the patients in both groups were treated with immunosuppressive therapy. At last follow-up (median 4.8 years), complete remission rate of proteinuria was significantly higher in patients with C3GN (64.3%) than in those with IC-MPGN (29.9%; P = 0.015). The renal survival rate was lower in patients with IC-MPGN when compared to C3GN (73.1% vs. 100%; log-rank, P = 0.031). Systolic blood pressure and renal function at baseline were independent predictors of progression to end-stage kidney disease. The overall prognosis of patients with C3GN is more favorable than for patients with IC-MPGN.

Remdesivir is an antiviral drug that results in clinical improvement after five days of treatment and accelerates recovery by 31%. No studies have discussed the pharmacokinetic analysis of remdesivir in patients with severe COVID-19 requiring extracorporeal membrane oxygenation (ECMO). A 63-year-old American man who underwent mechanical ventilation and ECMO for severe COVID-19 was administered remdesivir for ten days. The loading dosage was 200 mg at 7 PM on day 12 and 100 mg daily at 0:00 PM from day 13–21, administered within 1 h. The pharmacokinetic analysis was performed. The serum creatinine concentration was within the normal range of 0.5–0.7 mg/dL during treatment. According to the pharmacokinetic analysis, the plasma concentrations of remdesivir and GS-441524 4 h after administration (C4) were 662 ng/mL and 58 ng/mL, respectively, and the concentrations 18 h after administration (C18) were 32 ng/mL and 44 ng/mL, respectively. Therefore, the half-life of remdesivir and GS-441524 was 3.2 and 35.1 h, respectively. Monitoring the plasma concentrations of remdesivir and GS-441524 in patients undergoing ECMO may be necessary.

Causal relations among many statistical variables have been assessed using a Linear non-Gaussian Acyclic Model (LiNGAM). Using access to large amounts of health checkup data from Osaka prefecture obtained during the six fiscal years of years 2012-2017, we applied the DirectLiNGAM algorithm as a trial to extract causal relations among health indices for age groups and genders. Results show that LiNGAM yields interesting and reasonable results, suggesting causal relations and correlation among the statistical indices used for these analyses.

Lard diet (LD) is a risk factor for prostate cancer (PCa) development and progression. Two immunocompetent mouse models fed with isocaloric specific fat diets (LD) enriched in saturated and monounsaturated fatty acid (SMFA), showed significanftly enhanced PCa progression with weight gain compared with a fish oil diet (FOD). High gut microbial divergency resulted from difference in diets, and the abundance of several bacterial species, such as in the orders Clostridiales and Lactobacillales, was markedly altered in the feces of LD- or FOD-fed mice. The proportion of the order Lactobacillales in the gut was negatively involved in SMFA-induced body weight gain and PCa progression. We found the modulation of lipid metabolism and cholesterol biosynthesis pathways with three and seven commonly up- and downregulated genes in PCa tissues, and some of them correlated with the abundance of the order Lactobacillales in mouse gut. The expression of sphingosine 1-phosphate receptor 2, which is associated with the order Lactobacillales and cancer progression in mouse models, was inversely associated with aggressive phenotype and weight gain in patients with PCa using the NCBI Gene Expression Omnibus database. Therefore, SMFA may promote PCa progression with the abundance of specific gut microbial species and overexpression of lipogenic genes in PCa. Therapeutics with alteration of gut microbiota and candidate genes involved in diet-induced PCa progression may be attractive in PCa.

BackgroundHigh-quality training is required to improve the cardiopulmonary resuscitation (CPR) skills. Although it has been reported that the use of a feedback device is effective, the effects of feedback timing and frequency on CPR training have not been investigated. The aim of this study was to clarify the influence of feedback frequency and timing on the acquisition of CPR skills.MethodsSixty-eight undergraduates were first divided into female (n = 32) and male (n = 36) groups, and randomly assigned to one of four groups for each sex: concurrent-100%, concurrent-50%, terminal-100%, and terminal-50% feedback groups. The randomization was performed using a lottery method. This study consisted of a pre-test, practice sessions, a post-test, and a follow-up test. In the practice sessions, the participants performed six 2-minute CPR sessions in accordance with the condition assigned using mannequins and feedback devices. The post-test was conducted 24 hours after the completion of the practice sessions and the follow-up test was conducted 3 months after the completion of the practice sessions. The primary outcome of the study was the overall score at the follow-up test.ResultsThe results of the overall score at the follow-up test for each group were 88.2 ± 9.6% for concurrent-100%, 92.2 ± 6.4% for concurrent-50%, 82.6 ± 16.4% for terminal-100%, and 85.2 ± 16.9% for terminal-50%. We did not find any statistically significant difference for the overall score at the follow-up test among the four groups (p = 0.173). The ANOVA for the test sessions revealed that there were no significant main effects of feedback timing (p = 0.135) or frequency (p = 0.765), and no significant interaction between timing and frequency (p = 0.997).ConclusionThe present study reveals that the use of feedback devices is an important factor for higher quality CPR training, regardless of the timing and frequency with which they are used.

Although multiple studies have identified skipping breakfast as a risk factor for weight gain, there is limited evidence on the clinical impact of skipping lunch and dinner on weight gain. This retrospective cohort study including 17,573 male and 8860 female university students at a national university in Japan, assessed the association of the frequency of breakfast, lunch, and dinner with the incidence of weight gain (≥10%) and overweight/obesity (body mass index ≥ 25 kg/m2), using annual participant health checkup data. Within the observation period of 3.0 ± 0.9 years, the incidence of ≥10% weight gain was observed in 1896 (10.8%) men and 1518 (17.1%) women, respectively. Skipping dinner was identified as a significant predictor of weight gain in multivariable-adjusted Poisson regression models for both men and women (skipping ≥ occasionally vs. eating every day, adjusted incidence rate ratios, 1.42 (95% confidence interval: 1.02–1.98) and 1.67 (1.33–2.09) in male and female students, respectively), whereas skipping breakfast and lunch were not. Similarly, skipping dinner, not breakfast or lunch, was associated with overweight/obesity (1.74 (1.07–2.84) and 1.68 (1.02–2.78) in men and women, respectively). In conclusion, skipping dinner predicted the incidence of weight gain and overweight/obesity in university students.

Although multiple studies have revealed a close association of skipping breakfast with cardiometabolic diseases, few studies have reported its association with chronic kidney disease (CKD). Furthermore, there is scant reporting on the clinical impacts that skipping lunch and dinner has on cardiometabolic diseases and CKD. This retrospective cohort study, including 5439 female and 4674 male workers of a national university in Japan who underwent annual health checkups between January 2005 and March 2013, aimed to assess an association of frequencies of breakfast, lunch, and dinner with incidence of proteinuria (dipstick urinary protein ≥1+). The incidence of proteinuria was observed in 763 (14.0%) females and 617 (13.2%) males during the median 4.3 and 5.9 years of the observational period, respectively. In females, skipping breakfast as well as skipping dinner, but not lunch, were associated with the incidence of proteinuria (adjusted hazard ratios of breakfast frequency of “every day”, “sometimes”, and “rarely”: 1.00 (reference), 1.35 (1.09–1.66), and 1.54 (1.22–1.94), respectively; those of dinner frequency of “every day” and “≤sometimes”: 1.00 (reference) and 1.31 (1.00–1.72), respectively). However, no association was observed in male workers. Skipping breakfast and skipping dinner were identified as risk factors of proteinuria in females, but not in males.

BACKGROUND:Immunoglobulin A nephropathy (IgAN) is one of most common forms of glomerulonephritis. At this point, the clinical impact of hyperuricemia on IgAN is not clear. The aim of the present study was to explore the clinical impact of hyperuricemia on the progression of IgAN. STUDY DESIGN:Multicenter retrospective cohort study. SETTING & PARTICIPANTS:935 IgAN patients who were diagnosed by kidney biopsy at Osaka University Hospital, Osaka General Hospital, and Osaka Rosai Hospital. were included in this study. PREDICTOR:Uric acid levels at renal biopsy. OUTCOMES:The outcome of interest was the time from the kidney biopsy to the time when a 50% increase in the baseline serum creatinine level was observed, which was defined as "progression". MEASUREMENTS:The baseline characteristics according to the kidney biopsy at the time of diagnosis were collected from the medical records, and included age, gender, body mass index, hypertension, diabetes (use of antidiabetic drugs), serum levels of creatinine, urinary protein, smoking status, RAAS blockers and steroid therapy. RESULTS:An elevated serum uric acid level was an independent risk factor for progression in female patients (per 1.0 mg/dL, multivariate-adjusted incident rate ratio 1.33 [95% confidence interval 1.07, 1.64], P = 0.008) but not in male patients (1.02 [0.81, 1.29], P = 0.855). To control a confounding effect of renal function on an association between serum uric acid level and progression in female patients, age- and serum creatinine-matched and propensity score-matched analyses were performed, and these results also supported the effect by uric acid on kidney disease progression independent of basal kidney function. LIMITATIONS:A cohort analyzed retorospectively. CONCLUSIONS:This study revealed that an elevated uric acid level was an independent risk factor for ESKD in female IgAN patients. Therefore, uric acid might be a treatable target in female IgAN patients.

Diagnosis of chronic glomerulonephritis (CGN) depends primarily on renal biopsy, which is expensive and requires hospitalization, creating a demand for noninvasive diagnostic method for this disease. We used DNA microarray analysis to search for genes whose expression levels in peripheral blood mononuclear cells (PBMCs) could distinguish between patients with CGN and healthy volunteers (HVs). We selected immunoglobulin A nephropathy (IgAN) and membranous nephropathy (MN) as typical forms of CGN. The mRNA level of the gene encoding interferon (IFN)-alpha-inducible protein 27, IFI27, which is preferentially expressed in podocytes of glomeruli, was lower in PBMCs of IgAN and MN patients than in those of HVs. This result was confirmed by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Moreover, qRT-PCR analysis revealed that the IFI27 mRNA level was reduced in PBMCs of patients with other types of chronic glomerulonephritis. IFI27 immunohistochemical staining of biopsied specimens also confirmed reduced expression of IFI27 protein in IgAN and MN patients. Based on these results, we propose that IFI27 could serve as a noninvasive diagnostic marker for CGNs using peripheral blood.

BACKGROUND:The Agatston score, commonly used to quantify coronary artery calcification (CAC), is determined by the plaque area and density. Despite an excellent predictability of the Agatston score for cardiovascular events, the density of CAC has never been studied in patients with pre-dialysis chronic kidney disease (CKD). This study aimed to analyze the CAC density and its association with serum mineral levels in CKD. METHODS:We enrolled patients with pre-dialysis CKD who had diabetes mellitus, prior cardiovascular disease history, elevated low-density lipoprotein cholesterol levels, or smoking history. The average CAC density was calculated by dividing the Agatston score by the total area of CAC. RESULTS:The mean estimated glomerular filtration rate (eGFR) of 109 enrolled patients was 35.7 mL/min/1.73 m2. The correlation of the Agatston score with density was much weaker than that with the total area (R2 = 0.19, P < 0.001; and R2 = 0.99, P < 0.001, respectively). Multivariate analyses showed that serum magnesium level was inversely associated with the density, but not with the total area, after adjustment for demographics and clinical factors related to malnutrition-inflammation-atherosclerosis syndrome and mineral and bone disorders including fibroblast growth factor 23 (P = 0.006). This inverse association was pronounced among patients with higher serum phosphate levels (P for interaction = 0.02). CONCLUSION:CAC density was inversely associated with serum magnesium levels, particularly in patients with higher serum phosphate levels.

While tacrolimus and everolimus have common metabolic pathways through CYP3A4/5, tacrolimus is metabolized solely by CYP3A4 in recipients with the CYP3A5*3/*3. The purpose of this study was to evaluate how the area under the blood concentration-time curves (AUC) of tacrolimus could be predicted based on CYP3A5 genotype and the AUC of everolimus in renal transplant patients taking both drugs. The dose-adjusted AUC (AUC/D) of tacrolimus and everolimus were calculated at one month and one year after transplantation. Significant correlations between the AUC/D of tacrolimus and everolimus were found for patients with the CYP3A5*1 allele or CYP3A5*3/*3 at both one month and one year. At both stages, the determination coefficients were higher and the slopes of regression equations were larger for patients with CYP3A5*3/*3 compared to the CYP3A5*1 allele. A good correlation between single doses of tacrolimus and everolimus was found for CYP3A5*3/*3 patients at 1 year after transplantation (r = 0.794, p < 0.001). The variability of the AUC0–24/D of tacrolimus for each CYP3A5 genotype could be predicted based on the AUC0–12/D of everolimus. Clinicians may be able to comprehensively carry out the dose adjustments of tacrolimus and everolimus based on relationship with AUCs of both drugs in each CYP3A5 genotype.

BackgroundImmunoglobulin (Ig)A nephropathy (IgAN) is the most common form of primary glomerulonephritis in the world. Some bacteria were reported to be the candidate of the antigen or the pathogenesis of IgAN, but systematic analysis of bacterial flora in tonsil with IgAN has not been reported. Moreover, these bacteria specific to IgAN might be candidate for the indicator which can predict the remission of IgAN treated by the combination of tonsillectomy and steroid pulse.Methods and findingsWe made a comprehensive analysis of tonsil flora in 68 IgAN patients and 28 control patients using Denaturing gradient gel electrophoresis methods. We also analyzed the relationship between several bacteria specific to the IgAN and the prognosis of the IgAN. Treponema sp. were identified in 24% IgAN patients, while in 7% control patients (P = 0.062). Haemophilus segnis were detected in 53% IgAN patients, while in 25% control patients (P = 0.012). Campylobacter rectus were identified in 49% IgAN patients, while in 14% control patients (P = 0.002). Multiple Cox proportional-hazards model revealed that Treponema sp. or Campylobactor rectus are significant for the remission of proteinuria (Hazard ratio 2.35, p = 0.019). There was significant difference in remission rates between IgAN patients with Treponema sp. and those without the bacterium (p = 0.046), and in remission rates between IgAN patients with Campylobacter rectus and those without the bacterium (p = 0.037) by Kaplan-Meier analysis. Those bacteria are well known to be related with the periodontal disease. Periodontal bacteria has known to cause immune reaction and many diseases, and also might cause IgA nephropathy.ConclusionThis insight into IgAN might be useful for diagnosis of the IgAN patients and the decision of treatment of IgAN.

BACKGROUND: Multiple studies have shown cigarette smoking to be a risk factor for chronic kidney disease. However, it is unknown whether smoking similarly increases the risk for progression of membranous nephropathy. METHODS: This study used the Nagoya Nephrotic Syndrome Cohort Study (N-NSCS), including 171 patients with idiopathic membranous nephropathy (IMN) from 10 nephrology centers in Japan. The dose-response relationships between cigarette smoking and the outcomes were assessed by using multivariate Cox proportional hazards models adjusted for clinically relevant factors. The primary outcome was a 30% decline in the estimated glomerular filtration rate (eGFR). The secondary outcome was first complete remission (CR) of proteinuria. RESULTS: During the observation period (median, 37 months; interquartile range, 16-71 months), 37 (21.6%) patients developed a 30% decline in eGFR and 2 (1.2%) progressed to ESRD. CR occurred in 103 (60.2%) patients. Multivariate Cox proportional hazards models revealed current smoking (adjusted hazard ratio [HR], 7.81 [95% confidence interval (CI), 3.17-19.7]), female sex (adjusted HR, 3.58 [95% CI, 1.87-8.00]), older age (adjusted HR, 1.71 [95% CI, 1.13-2.62] per 10 years), the number of cigarettes smoked daily (adjusted HR, 1.61 [95% CI, 1.23-2.09] per 10 cigarettes daily), and cumulative smoking of ≥40 pack-years (adjusted HR, 5.56 [95% CI, 2.17-14.6]) to be associated with a 30% decline in eGFR. However, smoking was not associated with CR. CONCLUSION: Smoking is a significant and dose-dependent risk factor for IMN progression. All patients with IMN who smoke should be encouraged to quit.