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Background: Neuromodulation through spinal cord stimulation (SCS) is a therapeutic option for relieving leg pain and improving the chances of limb salvage in patients with intractable chronic limb‐threatening ischemia (CLTI); however, there is no consensus on its indications. Objective: The aim of this study was to assess the clinical outcomes of SCS in patients with intractable leg pain caused by various diseases treated in the department of cardiovascular medicine in Japan. Methods: This was a retrospective study of patients who underwent SCS for pain management. Patients were considered eligible for the therapy if they met the following criteria: (1) intractable leg pain (numerical rating scale [NRS] score of 10), (2) no revascularization option, and (3) no septicemia. Results: Twenty patients (mean age: 77 years; men/women: 11/9) were included in this study. The NRS score of the patients significantly reduced from 10 ± 0 before procedure to 4 ± 3 at discharge (p < 0.001). The clinical response rate of the entire cohort was 65% (13/20) at 17 ± 14 months after implantation; however, patients with intractable CLTI showed a low response rate (45%), whereas those with subacute limb ischemia showed a high response rate (100%). A multivariable regression analysis showed that hemoglobin level was significantly associated with treatment response, even after adjusting for age and sex (p = 0.026). The area under the receiver operating characteristic curve for the correlation between hemoglobin level (cutoff, 11.4 g/dL) and clinical response to SCS was 0.824 (0.619–1). Conclusions: SCS can reduce clinical symptoms in majority of patients with intractable leg pain. Although implantation of an SCS device has been shown to improve microvascular perfusion insufficiency, the correlation between hemoglobin level and the clinical effect of SCS indicates that a preserved microcirculatory vascular bed is essential for the therapy to be effective. [ABSTRACT FROM AUTHOR]

Objective This study aimed to establish prediction models for respiratory-related mortality in microscopic polyangiitis (MPA) complicated by interstitial lung disease (ILD) using clinical characteristics. Methods We enrolled patients with MPA with ILD between May 2005 and June 2021 in a multicentre cohort of Japanese patients with MPA (REVEAL cohort). We evaluated the demographic, clinical, laboratory, radiological findings, treatments and the presence of honeycombing 1 cm above the diaphragm using chest high-resolution CT (HRCT) on admission. We explored the risk factors predictive of respiratory-related mortality. Results Of 115 patients, 26 cases died of respiratory-related diseases during a median follow-up of 3.8 years. Eighteen patients (69%) died due to respiratory infection, three (12%) had diffuse alveolar haemorrhage, and five (19%) had exacerbation of ILD. In univariate analysis, older age, lower percent forced vital capacity (%FVC), lower percent diffusing capacity of carbon monoxide (%DLCO), and the presence of honeycombing in the right lower lobe were identified as risk factors. Additionally, in multivariate analysis adjusted for age and treatment, %FVC, %DLCO and the presence of honeycombing in the right lower lobe were independently associated with respiratory-related mortality. We created prediction models based on the values of %FVC, %DLCO and presence of honeycombing on chest HRCT (termed "MPF model"). The 5-year respiratory-related death-free rate was significantly different between patients with MPA with ILD stratified by the number of risk factors based on the MPF model. Conclusions Our study indicates that the MPF model may help predict respiratory-related death in patients with MPA with ILD. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to investigate the effects of diabetes care on periodontal inflammation. Materials and Methods: This prospective cohort study included 51 Japanese patients with type 2 diabetes who underwent intensive diabetes care including educational hospitalization and regular outpatient treatment for 6 months. Dental prophylaxis without subgingival scaling was provided three times during the observational period. Associations between changes in periodontal parameters and glycaemic control levels were evaluated using multiple regression analysis. Results: Overall, 33 participants (mean age: 58.7 ± 12.9) were followed up for 6 months. At baseline examination, 82% were diagnosed with Stage III or IV periodontitis. Haemoglobin A1c (HbA1c) level changed from 9.6 ± 1.8% at baseline to 7.4 ± 1.3% at 6 months. The ratio of probing pocket depth (PPD) ≥4 mm, bleeding on probing (BOP), full‐mouth plaque control record (PCR), periodontal epithelial surface area (PESA) and periodontal inflamed surface area (PISA) also significantly improved. The reduction in PPD and PESA was significantly associated with changes in both HbA1c and fasting plasma glucose (FPG) levels, and the reduction in PISA was significantly associated with an improvement in FPG after adjusting for smoking, change in body mass index and full‐mouth PCR. Conclusions: This is the first study to report a significant improvement in PPD and BOP after intensive diabetes care and dental prophylaxis without subgingival scaling. Clinical trial registration number: UMIN000040218. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to evaluate a human rights-informed dementia prevention program promoting better health and social care among older adults. In this study, the authors examined whether a dual-task training would improve cognition in healthy older adults. Design/methodology/approach: Individuals attending the systematic health education program for older adults based in Japan were recruited for study inclusion, and divided into a dual-task training group (TG) and a control group (CG). The TG underwent 90 min of a weekly dual-task training for 12 weeks. Severity of dementia was measured using the Mini-Mental State Examination (MMSE) test. Brain function was assessed using a go/no-go task paradigm, during which cerebral blood flow was additionally measured using functional near-infrared spectroscopy to quantify oxyhemoglobin (oxy-Hb). Findings: MMSE total score, number of errors in the go/no-go tasks and oxy-Hb values showed significant improvements in the TG. Research limitations/implications: Owing to the small number of participants allocated to the CG, the results must be interpreted with caution. Replication and further validation based on large-scale, randomized-controlled trials is warranted. Practical implications: This study highlights potential benefits of incorporating an early prevention training for dementia into a human rights-friendly health education program. Social implications: This study suggests a potential means to reduce costs of social security and health care by introducing a human rights-informed dementia prevention program. Originality/value: The results suggest that dual-task training may improve cognitive function in healthy older adults, thereby contributing to better health and improvement of social health care, based on a human rights-informed health education program for the prevention of dementia. [ABSTRACT FROM AUTHOR]

Simple Summary: The development of biomarkers that can predict the effectiveness of treatments for metastatic castration-resistant prostate cancer (mCRPC) has been a recent challenge. We focused on the efficacy of circulating tumor cell (CTC) status as a prognostic biomarker after enzalutamide administration. A retrospective subgroup analysis and prognostic survey were conducted on 43 patients with mCRPC and bone metastases. The results showed that patients with no detected CTCs at baseline showed significantly longer overall survival (OS) than those with CTCs at baseline. Furthermore, patients who exhibited a negative reversion of CTC status during enzalutamide treatment had significantly longer OS compared to patients with persistent CTC positivity. Achieving CTC-negative reversion during treatment for mCRPC with bone metastases was associated with improved long-term OS. Chronological measurement of CTC status might be clinically useful in the treatment of mCRPC. Enzalutamide is a second-generation androgen receptor inhibitor that increases overall survival (OS) rates in patients with metastatic castration-resistant prostate cancer (mCRPC). This study evaluates the efficacy of circulating tumor cell (CTC) status as a prognostic biomarker following enzalutamide administration. A retrospective subgroup analysis and prognostic survey were conducted on 43 patients with mCRPC and bone metastases treated in Juntendo University-affiliated hospitals from 2015 to 2022. Patients were treated with 160 mg enzalutamide daily. CTC analyses on blood samples were performed regularly before and every three months after treatment. The relationship between the patients' clinical factors and the OS rate was analyzed using the log-rank test; the median OS was 37 months. Patients with no detected CTCs at baseline showed significantly longer OS than those with detectable CTCs at baseline. Furthermore, patients demonstrating negative reversion of CTCs during enzalutamide treatment had significantly longer OS than patients with CTC-positivity. Two biomarkers—higher hemoglobin at baseline and achieving negative reversion of CTCs—were significantly associated with prolonged OS. This study suggests that patients achieving CTC-negative reversion during treatment for mCRPC with bone metastases exhibit improved long-term OS. Chronological measurement of CTC status might be clinically useful in the treatment of mCRPC. [ABSTRACT FROM AUTHOR]

Objectives Anaemia, a common comorbidity of RA, is related to high disease activity and poor prognosis. It is unknown which biologic/targeted synthetic (b/ts)-DMARDs are optimal for patients with anaemia and RA in regulating anaemia and controlling disease activity. Methods We investigated the change in haemoglobin (Hb) levels, drug retention rates and disease activities after the administration of b/ts-DMARDs with different modes of action [TNF inhibitors (TNFis), immunoglobulin fused with cytotoxic T-lymphocyte antigen (CTLA-4-Ig), IL-6 receptor inhibitors (IL-6Ris) and Janus kinase inhibitors (JAKis)] in patients with RA stratified by baseline Hb levels using the multicentre observational registry for patients with RA in Japan (ANSWER cohort). Results A total of 2093 patients with RA were classified into three groups based on tertiles of the baseline Hb levels (Hblow, anaemic; Hbint, intermediate; Hbhigh, non-anaemic). IL-6Ri increased Hb levels in all groups (the mean change at 12 months in Hblow was +1.5 g/dl, Hbint +0.7 g/dl and Hbhigh +0.1 g/dl). JAKis increased the Hb level in patients with anaemia and RA and retained or decreased the Hb level in non-anaemic patients (the mean change at 12 months in Hblow was +0.6 g/dl, Hbint 0 g/dl and Hbhigh −0.3 g/dl). In patients with anaemia and RA, overall adjusted 3-year drug retention rates were higher in JAKi followed by IL-6Ri, CTLA4-Ig and TNFi (78.6%, 67.9%, 61.8% and 50.8%, respectively). Change of disease activity at 12 months was not different among different b/ts-DMARDs treatments. Conclusion IL-6Ri and JAKi can effectively treat patients with anaemia and RA in a real-world setting. [ABSTRACT FROM AUTHOR]

The Park‐Bench Position (PBP) is associated with a high incidence rate of intraoperatively acquired pressure injuries (IAPIs). Preventive measures must be established to prevent the development of IAPIs. We investigated the risk factors for PBP by applying a soft silicone multilayered foam dressing (SMD) under core temperature management to prevent IAPIs. We conducted a prospective, single‐centre, open‐label observational study of patients undergoing elective neurosurgery operations using PBP in a university hospital in Japan. The incidence rate of IAPIs in this study was compared with that in our two previous studies, in which a film dressing was applied and core temperature management was not performed. IAPIs developed in 90 patients (6.7%); in the lateral thoracic region in five patients and the iliac crest region in one patient. The operative time (every 1 h: p = 0.0001, OR: odds ratio 3.62, 95% CI: confidence interval 1.73–11.42) was significantly associated with the incidence of IAPIs. In our two previous studies, the incidence rate of IAPIs was 11.0% and 24.1%, respectively, when film dressing was used. SMD may weaken the involvement of risk factors in IAPIs. [ABSTRACT FROM AUTHOR]

Local low‐frequency vibration promotes blood flow and wound healing in hard‐to‐heal diabetic foot ulcers (DFUs). However, vibration treatment is challenging in patients with DFUs due to wound management difficulties and low adherence. Consequently, developing wearable self‐care devices becomes imperative for effective wound healing. This study introduces a wearable vibration dressing and assesses its impact on wound healing in hyperglycemic rats. Low‐frequency vibration at 52 Hz was applied to the wound for 40 min/day in awake rats. Relative wound areas on post‐wounding days (PWDs) 4–7 were significantly smaller and the wound closure rate was significantly higher in the vibration group than in the control group (p < 0.05, respectively). The total haemoglobin at baseline and after vibration on post‐wounding day 7 was significantly larger in the vibration group than in the control group (p < 0.05). On PWD 7, the thickness of the granulation tissue was significantly higher in the vibration group than in the control group (p < 0.05). Moreover, the number of blood vessels at the wound site and vascular endothelial growth factor A protein expression were significantly higher in the vibration group than in the control group (p < 0.05, respectively). The ratio of (CD68+/iNOS+)/(CD163+) macrophages in the vibration group was significantly lower than that in the control group (p < 0.05). These results indicate the potential of wearable vibration dressings as new self‐care devices that can promote angiogenesis and blood flow, improve inflammation, and enhance wound healing in DFUs. [ABSTRACT FROM AUTHOR]

Aim: The effects of statins on muscle health are not well established. Therefore, this study investigated the impact of statin use on muscle strength and mass recovery in patients with sarcopenia after stroke. Methods: This retrospective cohort study included stroke patients with sarcopenia hospitalized between 2015 and 2021 at a post‐acute rehabilitation hospital. Sarcopenia was diagnosed using handgrip strength and skeletal muscle mass index measured using bioelectrical impedance analysis according to the 2019 criteria of the Asian Working Group for Sarcopenia. The study outcomes included handgrip strength and skeletal muscle mass index at hospital discharge. We used multivariate analyses to examine whether statin use was independently associated with the outcomes. Statistical significance was set at P < 0.05. Results: Of the 586 patients enrolled, 241 (mean age 79.3 years, 44.4% men) presented with sarcopenia and were included in the analysis. Statin use was observed in 61 (25.3%) patients. Statin use was independently negatively associated with handgrip strength at discharge (β = −0.095, P = 0.032), but not with skeletal muscle mass index at discharge (β = 0.019, P = 0.692). Conclusions: Statin use was negatively associated with muscle strength recovery, but not with muscle mass in patients with sarcopenia who underwent rehabilitation after stroke. To maximize outcomes, sufficient consideration is needed for statin use in these patients. Geriatr Gerontol Int 2023; 23: 676–683. [ABSTRACT FROM AUTHOR]

Background: Anemia is encountered in patients with nonvalvular atrial fibrillation (NVAF) on oral anticoagulants (OACs) but the prognostic impact was not well scrutinized in real‐world settings. Methods: We conducted a historical multicenter registry of patients with NVAF taking OACs at 71 centers in Japan. Those with mechanical heart valves or a history of pulmonary thrombosis or deep venous thrombosis were excluded. Anemic patients were divided into three groups of hemoglobin (Hb) level: moderate/severe (Hb < 11.0 g/dL), mild (men: Hb of 11.0–12.9 g/dL; women: Hb of 11.0–11.9 g/dL), and no anemia. The endpoints included major bleeding, hemorrhagic stroke, ischemic events, ischemic stroke, and all‐cause mortality. Results: Among 7558 consecutive patients (mean age, 73 years; men 67%) registered in February 2013 and followed until February 2017, 2100 (28%) patients had anemia. The anemic patients were older (moderate/severe: 79 years; mild: 77 years; no anemia: 71 years, p <.001), and HAS‐BLED score was significantly higher in the anemic patients (p <.001). The cumulative incidences at 4 years of major bleeding in moderate/severe, mild, and no anemia group, were 14.9%, 10.7%, and 6.4%, respectively. The adjusted hazard ratios (HRs) (95% confidential intervals (CIs)) of major bleeding of moderate/severe and mild anemia group were 1.96 (1.49–2.58) and 1.48 (1.17–1.87) compared to no anemia group. The adjusted HRs (95% CIs) for ischemic events were 0.63 (0.39–0.99) and 1.03 (0.76–1.39). Conclusions: The severity of anemia in the patients with NVAF on OACs was associated with major bleeding. [ABSTRACT FROM AUTHOR]

Anemia is prevalent in pregnant women, and the causes include inadequate diet, increased demand for iron, and inflammation. We hypothesized that gestational diabetes mellitus (GDM) and hepcidin-related gene polymorphisms may contribute to maternal anemia and that an anti-inflammatory diet can alleviate this negative effect. The aim of this study was to investigate the association of an inflammatory diet, GDM, and single nucleotide polymorphisms (SNPs) in hepcidin-related genes, which are key regulators of iron, with maternal anemia. This was a secondary data analysis of a prospective prenatal diet and pregnancy outcome study in Japan. The Energy-Adjusted Dietary Inflammatory Index was calculated using a brief self-administered diet history questionnaire. We analyzed 121 SNPs in 4 genes: TMPRS6 (43 SNPs), TF (39 SNPs), HFE (15 SNPs), and MTHFR (24 SNPs). Multivariate regression analysis was conducted to determine the association between the first variable and maternal anemia. The prevalence of anemia in first, second, and third trimesters were 5.4%, 34.9%, and 45.8%, respectively. The pregnant women with GDM had a significantly higher incidence of moderate anemia than those without GDM (40.0% vs. 11.4%, P =.029). In multivariate regression analysis, Energy-adjusted Dietary Inflammatory Index (β = −0.057, P =.011) and GDM (β = −0.657, P =.037) were significantly associated with hemoglobin levels during the third trimester. Using Stata's qtlsnp command, TMPRSS6 rs2235321 was found to be associated with hemoglobin levels during the third trimester. These results indicate that inflammatory diets, GDM, and TMPRSS6 rs2235321 polymorphism are associated with maternal anemia. This result suggests that a pro-inflammatory diet and GDM are associated with maternal anemia. Dietary quality was assessed using the Energy-Adjusted Dietary Inflammatory Index (E-DII) in a cohort of 169 pregnant Japanese women. Moderate anemia (hemoglobin <10.0 g/dL) was more frequently observed in the gestational diabetes mellitus (GDM) group than in the non-GDM group. Lower hemoglobin levels during the third trimester were attributed to both high E-DII score (B = −0.057) and GDM (B = −0.657). Additionally, hemoglobin levels during the third trimester were significantly associated with the rs2235321 variant of TMPRSS6. [Display omitted] [ABSTRACT FROM AUTHOR]

Aim: To investigate the association between locomotive syndrome and anemia among community‐dwelling older adults. Methods: This cross‐sectional study was conducted at specific health checkup centers in Japan between 2019 and 2020. We sent a questionnaire to older adults aged ≥65 years who participated in health checkups. A total of 2507 community‐dwelling older adults were included in this study (mean age = 72.3 years, 51.4% women). Locomotive syndrome was measured using a 25‐question Geriatric Locomotive Function Scale with a score range of 0–100, and was defined as ≥16 points. Anemia was defined using World Health Organization criteria, as a hemoglobin concentration of <13.0 g/dL in men and <12.0 g/dL in women. Logistic regression analyses were performed to investigate the association between locomotive syndrome and anemia, adjusted for age, sex, body mass index, depression symptoms, self‐reported comorbidities (cancer, rheumatoid arthritis, knee osteoarthritis, fractures, and spinal disease), hypertension, and renal function. Results: Of all the participants, 11.6% had locomotive syndrome and 12.8% had anemia. Even after adjustment, a relationship between locomotive syndrome and anemia was observed (adjusted odds ratio = 1.9, 95% confidence interval = 1.3–2.7). Conclusions: Community‐dwelling older adults with anemia had a significantly higher prevalence of locomotive syndrome than those without. This finding suggests that older adults with anemia are at risk of locomotive syndrome, and appropriate measures should be taken for prevention. Geriatr Gerontol Int 2023; 23: 426–429. [ABSTRACT FROM AUTHOR]

Simple Summary: Unresectable biliary tract cancer has a poor prognosis, with insufficient response rates from the standard treatment. We developed a new combination therapy regimen of intra-arterial chemotherapy plus radiation therapy based on a retrospective study, and we found its high effectiveness in cases of some unresectable biliary tract cancers. Then, we conducted this prospective study, which demonstrated the benefits for some patients with unresectable biliary tract cancer, resulting in high clinical response and disease control rates of 71.4% and 100%, respectively. Furthermore, two patients converted to surgery, indicating its high potential as a preoperative therapeutic strategy to achieve a long-term prognosis. This treatment was considered tolerated due to the absence of treatment-related deaths. This prospective pilot study is an important step toward determining the usefulness and safety of intra-arterial chemotherapy plus radiation therapy, as well as its potential future utility. The standard treatment of unresectable biliary tract cancer (BTC) has shown an insufficient response rate (RR). Our retrospective setting revealed that a combination therapy consisting of intra-arterial chemotherapy plus radiation therapy (IAC + RT) provided a high RR and long-term survival benefits in unresectable BTC. This prospective study aimed to test the effectiveness and safety of IAC + RT as the first-line therapy. The regimen included one-shot IAC with cisplatin, 3–6 months of reservoir IAC (5-FU and cisplatin, q/week), and 50.4 Gy of external radiation. The primary endpoints include the RR, disease control rate, and adverse event rate. This study included seven patients with unresectable BTC without distant metastasis, with five cases classified as stage 4. RT was completed in all cases, and the median number of reservoir IAC sessions was 16. The RR was 57.1% for imaging and 71.4% for clinical assessment, and the disease control rate was 100%, indicating a high antitumor efficacy, which allowed two cases to be transferred to surgery. Five cases of leukopenia and neutropenia; four cases of thrombocytopenia; and two cases of hemoglobin depletion, pancreatic enzyme elevation, and cholangitis were observed, but with no treatment-related deaths. This study revealed a very high antitumor effect with IAC + RT for some unresectable BTC, and it could be useful for conversion therapy. [ABSTRACT FROM AUTHOR]

Introduction: This study examined the association between hemoglobin (Hb) levels and all-cause mortality in community-dwelling individuals in Japan. Methods: Participants were 1,243 males (62 ± 14 years old) and 1,754 females (64 ± 12 years old). The research was based on a follow-up study with 7- and 19-year intervals. Results: The follow-up survey revealed 448 male deaths (36.0% of male participants) and 419 female deaths (23.9% of female participants). Male participants' hazard ratio (HR) for all-cause mortality was significantly higher for groups whose Hb level was < 11.0 g/dL (HR: 2.39; 95% confidence interval [CI]: 1.28-4.47) or in the range 11.0-11.9 g/dL (2.11; 1.23-3.62) or 12.0-12.9 g/dL (1.66; 1.15-2.41) than for the reference group (14.0-14.9 g/dL). For female participants, the HR for all-cause mortality was significantly higher in groups whose Hb level was < 11.0 g/dL (1.91; 1.19-3.05), in the range 11.0-11.9 g/dL (1.44; 1.03-2.03), or ≥15.0 g/dL (1.77; 1.10-2.85) than for the reference group (13.0-13.9 g/dL). Conclusions: The study revealed a linear positive association between Hb levels and the risk of all-cause mortality for male participants. However, this association formed a J-shaped curve for female participants. [ABSTRACT FROM AUTHOR]

Aim: Single‐arm, open‐label, phase 3 study to evaluate the efficacy and safety of ferric derisomaltose (FDI) for iron deficiency anemia (IDA) in Japanese women with postpartum hemorrhage (PPH). Methods: Postpartum women aged 20–39 years with serum ferritin <25.0 ng/ml, hemoglobin (Hb) <10.0 g/dl, and blood loss ≥500 ml within 24 h post‐delivery were eligible to receive high‐dose intravenous FDI. The primary endpoint was the maximum change in Hb concentration by Week 8. Key secondary endpoints included change in iron parameters and percentage of patients with a total Edinburgh Postnatal Depression Score (EPDS) ≥9. Safety assessments included treatment‐emergent adverse events (TEAEs) and iron concentrations in maternal milk. Results: All (n = 21 [100.0%]) patients received the predetermined total iron dose by Day 8. Hb concentrations increased rapidly and significantly (p < 0.001) following FDI. Serum ferritin levels also increased rapidly and were maintained near or above the upper limit of normal reference value (250 ng/ml). Following FDI, two (9.5%) patients had a total EPDS score of ≥9. TEAEs occurred in 23 of 42 (54.8%) patients and neonates overall, including 18 of 21 (85.7%) patients and 5 of 21 (23.8%) neonates. TEAEs were mild in all adult patients and four neonates, and moderate in one neonate. Iron concentrations in maternal milk remained within normal reference values. Appropriate patient selection and patient‐adjusted dosage selection facilitated safe and effective administration of high‐dose (≥1000 mg) FDI. Conclusions: Rapid and sustained improvements in Hb and iron stores occurred following FDI for IDA with PPH, with no new safety signals identified. Clinical trial identifier: JapicCTI‐194888. [ABSTRACT FROM AUTHOR]

Objective: The hemoglobin glycation index (HGI) reflects biological variability in hemoglobin A1c. Even so, studies on the relationship between HGI and nonalcoholic fatty liver disease (NAFLD) are limited. Therefore, this study aimed to explore the relationship between HGI and NAFLD. In addition, the study also aimed to provide new methods to identify patients with a high risk for the development of NAFLD. Methods: This was a retrospective study based on physical examination data from Japan. Patients were divided into quartiles (Q1–Q4) according to their HGI level; the lowest quartile (Q1) was used as the reference group. Patents were also classified into two subgroups based on the presence or absence of NAFLD. Baseline characteristics between the groups were compared. Multivariate logistic regression analysis was used to investigate the association between the HGI and NAFLD. A mediation analysis examined the mediation relationship between HGI and NAFLD. Subgroup analyses were performed to the reliability of the results. Results: A total of 14280 patients were eligible for inclusion in this study; 2515 had NAFLD. Patients in the NAFLD group had higher levels of HGI than patients in the non-NAFLD group. Increases in HGI correlated with an increased risk of NAFLD. After adjusting for confounding factors, the multivariate logistic regression analysis revealed that HGI was positively related to the prevalence of NAFLD. In addition, mediation analysis showed that body mass index (BMI) partly mediated the indirect impact of HGI on NAFLD preference. Subgroup analyses were performed according to age, sex, smoking status, and waist circumference. Our results indicated that HGI significantly correlated with NAFLD in patients with one of the following factors: age ≤60 years, BMI >28 kg/m², female sex, a history of smoking, and abdominal obesity. Conclusions: HGI was an independent risk factor for NAFLD, and BMI partly mediated the association between HGI and NAFLD. [ABSTRACT FROM AUTHOR]

Enarodustat (JTZ-951) is a hypoxia-inducible factor prolyl hydroxylase inhibitor that has been approved and marketed in Japan for patients with anemia with chronic kidney disease (CKD). The pharmacometric approach was applied to assess the relationship between plasma concentrations of enarodustat and hemoglobin (Hb) levels, and to provide information regarding the optimal use of enarodustat in clinical practice by simulations based on the pharmacokinetic and pharmacodynamic (PK/PD) model that was developed. The PK/PD data of enarodusat obtained from phase 2 and phase 3 studies in Japanese patients with CKD were well described by the models: a 1-compartment model with first-order absorption and elimination for PK, and a semimechanistic model based on transit compartment model for PD. Although several factors were identified as statistically significant covariates on the PK/PD of enarodustat, model-based simulations showed that none of them had clinically relevant impacts on the treatment effect (ie, Hb levels) of enarodustat. Hence, enarodustat treatment provides the stable Hb control with the initial dose (hemodialysis-dependent CKD: 4 mg/day, non-dialysis-dependent CKD: 2 mg/day) and maintenance dose (1-8 mg/day) to the patients with varied demographic characteristics. [ABSTRACT FROM AUTHOR]

Background: After the Great East Japan Earthquake on March 11, 2011 and the subsequent accident at the Tokyo Electric Power Company‐operated Daiichi Nuclear Power Plant, the Fukushima Prefecture government initiated the Fukushima Health Management Survey (FHMS) to assess the long‐term health effects of the disaster on Fukushima residents. The blood tests of children aged ≤15 years between 2011 and 2012 did not reveal any changes regarding peripheral blood data; however, long‐term monitoring is still necessary. Therefore, this study aimed to investigate the long‐term health status of children aged ≤15 years who had evacuated the Fukushima Prefecture. Methods: From 2011 to 2018, 71,250 evacuees aged 15 years or younger participated in the FMHS and were subjected to blood tests. By analyzing the data of the comprehensive health check survey managed by the FHMS, we examined the changes in hemoglobin (Hb) levels, white blood cell (WBC) counts, including fractions, and platelet (PLT) counts among children from 2011 to 2018. Results: Minor fluctuations in Hb levels, PLT counts, and WBC counts were observed during the study period, but the central 95% intervals of distribution of the laboratory values were generally within previously reported reference intervals. In particular, there was no increase in the proportions of patients with anemia, polycythemia, or deviating WBC counts. Conclusion: From 2011 to 2018, there was no increase in the percentages of children with anemia, polycythemia, or deviating WBC counts among the Fukushima Prefecture evacuees. [ABSTRACT FROM AUTHOR]

Low birth weight (LBW), small for gestational age (SGA), and preterm birth (PTB) are important neonatal outcomes that may affect infant morbidity and mortality. The aim of this study is to investigate associations between maternal hemoglobin (Hb) concentrations and pregnancy outcomes of LBW, SGA, and PTB. This was a prospective birth cohort study using data of the Japan Environment and Children's Study. Participants were divided into five groups according to maternal Hb (g/dL) in the first and second trimesters: group 1, Hb < 9; group 2, 9 ≤ Hb < 11.0; group 3, 11.0 ≤ Hb < 13.0; group 4, 13.0 < Hb < 14.0; and group 5, 14.0 ≤ Hb. We examined the relationships between LBW, PTB, SGA, and maternal Hb in the first and second trimesters. Excluding 29,673, a total of 74,392 newborns (first trimester: n = 39,084, second trimester: n = 35,308) were included. We obtained adjusted odds ratios (aORs) (95% confidence intervals (CIs)) using multivariate analysis; compared with group 3 in the first trimesters, women in group 1 were at increased risk of PTB (aOR, 3.20; 95% CI, 1.69–6.09), LBW (aOR, 2.21; 95% CI, 1.19–4.09). In the second trimester, multivariate analysis revealed that, compared with group 3 in the second trimester, women in group 1 were at increased risk of PTB (aOR, 2.30; 95% CI, 1.19–4.42) and women in group 5 were at increased risk of LBW (aOR, 1.87; 95% CI, 1.24–2.81) and PTB (aOR, 1.73; 95% CI, 1.06–2.83). Elevated maternal Hb in the second trimester was associated with risks of PTB and LBW. [ABSTRACT FROM AUTHOR]

Although there are clear moral components to traffic violations and risky and aggressive driving behavior, few studies have examined the relationship between moral values and risky driving. This study aimed to examine the relationship between moral views of driving behavior and brain activity. Twenty healthy drivers participated in this study. A questionnaire regarding their moral values concerning driving behavior was administered to the participants. Brain activity was measured using near-infrared spectroscopy while eliciting moral emotions. Based on the results of the questionnaire, the participants were divided into two groups: one with high moral values and the other with low moral values. Brain activity was statistically compared between the two groups. Both groups had significantly lower activity in the prefrontal cortex during the self-risky driving task. The low moral group had significantly lower activity in the left dorsolateral prefrontal cortex than the high moral group, while it had lower activity in the right dorsolateral prefrontal cortex in the self-risky driving task than in the safe driving task. Regardless of their moral values, the participants were less susceptible to moral emotions during risky driving. Furthermore, our findings suggest that drivers with lower moral values may be even less susceptible to moral emotions. [ABSTRACT FROM AUTHOR]

Aims: Lower haemoglobin levels are common among females without kidney diseases. However, little is known about the sex‐specific management of anaemia in haemodialysis patients. Methods: This prospective cohort study investigated the role of sex differences in the association between categorical baseline or time‐varying haemoglobin levels and all‐cause mortality via cox regression using data from 6890 patients in the Japan Dialysis Outcomes and Practice Patterns Study (J‐DOPPS, 2005–2015). Likelihood ratio tests were used to evaluate the effect modification of sex on the relationship between haemoglobin and mortality. Results: A total of 781 patients died during the median follow‐up of 31 months. Mortality risk, adjusted for case mix, varied between five haemoglobin categories, with the highest category (≥12 g/dL) having a hazard ratio of 0.73 (0.41–1.29) for females and 2.02 (1.03–3.95) for males versus 10–10.9 g/dL. Despite this difference, the p‐value comparing the overall among males versus females was.35. Similar associations were observed in models stratified by patient age (<75 years), time on dialysis (≤1 year), and models lagging the haemoglobin exposure. Conclusion: The results based on this sample of Japanese haemodialysis patients did not support the hypothesis that the association between haemoglobin and survival differed by sex. We also could not conclude that the association was identical, as the parameter estimates are consistent with male patients having a relatively greater mortality risk than female patients at higher haemoglobin levels. More detailed investigations into the effects of higher haemoglobin levels by sex might help better understand strategies for anaemia management. Summary at a Glance: Haemoglobin levels in haemodialysis patients are known to be associated with survival. Despite women usually have lower haemoglobin levels than men, the results of this study did not strongly indicate that sex modifies the association between haemoglobin and survival. [ABSTRACT FROM AUTHOR]

Background: Diabetes and the etiology of breast cancer are clearly associated. However, the impact of diabetes on prognosis is not yet understood. Therefore, we conducted a retrospective cohort study to examine the relationship between diabetes and patient outcomes in breast cancer patients. Methods: We investigated 332 Japanese women with breast cancer who underwent curative surgery at our hospital. Patients without sufficient clinical information including hemoglobin A1c (HbA1c) and those with an observation period of less than 1 year were excluded. Results: Among the patients examined, 106 had diabetes at the time of their breast cancer diagnosis. Among the 296 patients with invasive breast carcinoma, 36 patients developed distant metastases during the mean observation period of 45 months. Sixteen patients died due to breast cancer, while 13 died of other causes. Multivariate analysis revealed that diabetes, tumor size, and estrogen receptor (ER) status were independent factors related to distant metastasis-free survival (DMFS) (p = 0.038, p < 0.001, and p = 0.006, respectively). Kaplan-Meier curve analysis revealed that diabetes negatively affected the outcomes of ER-negative breast cancer patients both in DMFS and overall survival (p = 0.045 and p = 0.029, respectively). Meanwhile, patient outcomes did not differ according to the level of HbA1c in diabetes patients. Conclusion: Patients with diabetes had a significantly shorter DMFS, and the negative effect of diabetes on patient outcomes was more evident in ER-negative breast cancer. Our data indicates the importance of primary prevention of diabetes for breast cancer patients. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Fat mass and fat‐free mass affect glycated hemoglobin A1c (HbA1c) levels and blood glucose levels, respectively. The aim of the present study was to examine the association between the fat mass index and fat‐free mass index with HbA1c. Materials and Methods: We carried out a cross‐sectional study that included 3,731 men and 9,191 women aged ≥20 years, living in Miyagi Prefecture, Japan, who were not treated for diabetes. The fat mass index and fat‐free mass index were calculated as fat mass and fat‐free mass divided by the height squared, respectively. The indices were classified into sex‐specific quartiles and combined into 16 groups. An analysis of covariance was used to assess associations between the combined fat mass index and fat‐free mass index with HbA1c adjusted for potential confounders. The linear trend test was carried out by stratifying the fat mass index and fat‐free mass index, entering the number as a continuous term in the regression model. Results: In multivariable models, a higher fat mass index was related to higher HbA1c levels in men and women in all fat‐free mass index subgroups (P < 0.001 for linear trend). When we excluded the participants who had been identified as having diabetes, the fat‐free mass index was also related to higher HbA1c levels in most fat mass index subgroups (P < 0.05 for linear trend). Conclusions: Fat mass index was positively related to HbA1c levels. The fat‐free mass index was also related to HbA1c levels when we excluded participants who had been identified as having have diabetes. [ABSTRACT FROM AUTHOR]

To determine prevalence of depressive symptoms and their associated factors in geriatric inpatient rehabilitation. A cross-sectional study was conducted with 118 older adult inpatients ≥ 65 years using the Geriatric Depression Scale to assess depressive symptoms. Average age of participants was 78.9 years old. Depressive symptoms were found in 46.6% of study participants. Multinomial logistic regression analysis was conducted to confirm the association between presence of depressive symptoms and each factor. Malnutrition was significantly associated with depressive symptoms (OR = 0.90, 95% CI: 0.87–0.96, p < 0.001). Similar results were obtained in model 1 (OR = 0.91, 95% CI: 0.87–0.95, p < 0.001) with the addition of age and gender confounders and in model 2 with additional adjustment for underlying disease, Functional Independence Measure (FIM) exercise items, and FIM cognitive items (OR = 0.92, 95% CI: 0.88–0.96, p < 0.001). Prevalence of depressive symptoms is high in geriatric rehabilitation patients and is associated with malnutrition. [ABSTRACT FROM AUTHOR]

The article describes the results of a study on the effectiveness of a combined therapy of rituximab and belimumab for the management of female Japanese patients with systemic lupus erythematosus-associated immune thrombocytopenia (SLE-ITP). Topics mentioned include the physical symptoms experienced by the patients, the influence of the combined therapy on the early withdrawal of glucocorticoid, and the cause of severe bleeding in primary ITP.

Background: Helicobacter pylori (H. pylori) infection causes various extragastric diseases. Its transmission route has still not been clarified. However, no large‐scale studies have examined the extragastric diseases caused by H. pylori in adolescents. This study aimed to examine the association of H. pylori infection with anemia, serum cholesterol levels, physique, and birth delivery method (vaginal or cesarean) in a large number of Japanese adolescents. Methods: From 2016 to 2018, we screened 2,399 adolescents (aged 13–15 years) in their second and third years of junior high school using an enzyme‐linked immunosorbent assay‐based antibody test. Red blood cells, hemoglobin, hematocrit, total cholesterol, high‐density lipoprotein (HDL) cholesterol, and serum antibody levels were measured. Results: Hemoglobin and hematocrit levels were significantly lower in the H. pylori antibody‐positive group than in the H. pylori antibody‐negative group in both sexes (boys: P = 0.0004 and 0.0022; girls: P = 0.0019 and 0.0005, respectively). Total cholesterol and non‐HDL cholesterol levels were significantly higher in the H. pylori‐positive group than in the H. pylori‐negative group among boys (P = 0.0370 and 0.0293 respectively). There was no significant difference in body mass index percentile and birth delivery method between the H. pylori‐positive and H. pylori‐negative groups in both boys and girls. Conclusions: Among Japanese junior high school students, H. pylori antibody‐positive status was associated with anemia in both sexes while total cholesterol and non‐HDL cholesterol levels were associated among boys. There was no association between H. pylori antibody status, body mass index percentile, and birth‐delivery method. [ABSTRACT FROM AUTHOR]

Background Vadadustat is an investigational, oral hypoxia-inducible factor prolyl hydroxylase inhibitor in development in Japan for the treatment of chronic kidney disease (CKD)-induced anemia. Methods Two Phase 2, multicenter, double-blind, placebo-controlled studies randomized Japanese patients with nondialysis-dependent (NDD, n  = 51) or dialysis-dependent (DD, n  = 60) CKD-induced anemia to once-daily vadadustat (150, 300 or 600 mg) or placebo. A 6-week, fixed-dose primary efficacy period was followed by a 10-week vadadustat dose adjustment/maintenance period. The primary endpoint was the mean change in hemoglobin (Hb) level from pretreatment to Week 6. Results Statistically significant (P < 0.01) dose-dependent increases in mean Hb values were observed at Week 6 in all vadadustat groups versus placebo [placebo and vadadustat 150, 300 and 600 mg: −0.47, 0.43, 1.13 and 1.62 (NDD-CKD) and −1.48, −0.28, 0.08 and 0.41 (DD-CKD), respectively]. By Week 16, 91% (NDD-CKD) and 71% (DD-CKD) of vadadustat-treated participants achieved target Hb levels (10.0–12.0 g/dL) and significant dose-dependent changes in iron utilization and mobilization biomarkers were observed with vadadustat. During the primary efficacy period, the incidence of treatment-emergent adverse events (AEs) with placebo and vadadustat 150, 300 and 600 mg was 36, 33, 58 and 54% (NDD-CKD) and 40, 53, 73 and 40% (DD-CKD), respectively. The most common AEs during the primary efficacy period were nausea and hypertension (NDD-CKD) and diarrhea, nasopharyngitis and shunt stenosis (DD-CKD). Of 23 serious AEs in 18 patients, 1 was deemed related (hepatic function abnormal); no deaths were reported. Conclusions The efficacy and safety results from these studies support the development of vadadustat for the treatment of anemia in patients with CKD. [ABSTRACT FROM AUTHOR]

Background: Although a tool for sharing patient prognosis among all medical staff is desirable in heart failure (HF) cases, only a few simple HF prognostic scores are available. We previously presented the A 2 B score, a simple user-friendly HF risk score, and validated it in a small single-center cohort. In the present study, we validated it in a larger nationwide cohort., Methods and Results: We examined the 2-year mortality in relation to the A 2 B scores in 3483 patients from a Japanese nationwide cohort and attempted to stratify their prognoses according to the scores. The A 2 B score was determined by assigning points for age, anemia, and brain natriuretic peptide (BNP) level at discharge: age (<65 years, 0; 65-74 years, 1; ≥75 years, 2), anemia (hemoglobin ≥12 g/dL, 0; 10-11.9 g/dL, 1; <10 g/dL, 2), and BNP (<200 pg/mL, 0; 200-499 pg/mL, 1; ≥500 pg/mL, 2). Hemoglobin and BNP levels were applied to the data at discharge. The 2-year survival rates for A 2 B scores 1, 2, 3, 4, 5, and 6 were 94.1%, 83.2%, 74.1%, 63.5%, 51.6%, and 41.5%, respectively; the mortality rate increased by ≈10% for each point increase (c-index, 0.702). The A 2 B score was applicable in HF cases with reduced or preserved ejection fraction and remained useful when BNP was substituted with N-terminal proBNP (c-index, 0.749, 0.676, and 0.682, respectively)., Conclusions: The A 2 B score showed a good prognostic value for HF in a large population even when BNP was replaced with N-terminal proBNP.

Objective: We investigated whether pretreatment systemic inflammatory markers are associated with survival outcomes in patients with endometrial cancer (EC)., Methods: Data from the Japanese Gynecologic Oncology Group 2043 were analyzed. Patients who did not receive chemotherapy or were lost to follow-up were excluded. Associations of pretreatment systemic inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and hemoglobin, albumin, lymphocyte, and platelet (HALP) score, with progression-free survival (PFS) and overall survival (OS) were analyzed. The optimal NLR, PLR, and HALP score cutoff values for PFS and OS were determined. Survival estimates were calculated and compared using the Kaplan-Meier method and log-rank test., Results: We included 712 patients (median age: 55 [range, 28-74] years; body mass index [BMI]: 21.1 [15.2-38.6] kg/m 2 ). For PFS, optimal NLR, PLR, and HALP score cutoff values were 1.48, 0.017, and 35.52, respectively, and for OS, the values were 1.88, 0.026, and 19.87, respectively. At optimal PFS-related cutoff values, NLR was associated with BMI; PLR with age, BMI, and clinical stage; and HALP score with BMI, clinical stage, and lymph node metastasis. At optimal OS-related cutoff values, NLR was associated with BMI, PLR, and BMI; the HALP score was associated with age and BMI. The HALP score was a prognostic factor for PFS (p = 0.025), while PLR and HALP scores were prognostic factors for OS (both p = 0.028)., Conclusions: Pretreatment systemic inflammatory markers are associated with survival outcomes in patients with EC, with the HALP score being a prognostic factor for PFS and OS., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: To quantify the changes of hemoglobin mass (Hbmass) and maximum oxygen consumption (VO2max) after 22 days training at 1300-1800 m combined with nightly exposure to 3000-m simulated altitude. We hypothesized that with simulated 3000-m altitude, an adequate beneficial dose could be as little as 10 h/24 h. Methods: Fourteen male collegiate runners were equally divided into 2 groups: altitude (ALT) and control (CON). Both groups spent 22 days at 1300-1800 m. ALT spent 10 h/night for 21 nights in simulated altitude (3000 m), and CON stayed at 1300 m. VO2max and Hbmass were measured twice before and once after the intervention. Blood was collected for assessment of percent reticulocytes (%retics), serum erythropoietin (EPO), ferritin, and soluble transferrin receptor (sTfR) concentrations. Results: Compared with CON there was an almost certain increase in absolute VO2max (8.6%, 90% confidence interval 4.8-12.6%) and a likely increase in absolute Hbmass (3.5%; 0.9-6.2%) at postintervention. The %retics were at least very likely higher in ALT than in CON throughout the 21 nights, and sTfR was also very likely higher in the ALT group until day 17. EPO of ALT was likely higher than that of CON on days 1 and 5 at altitude, whereas serum ferritin was likely lower in ALT than CON for most of the intervention. Conclusions: Together the combination of the natural and simulated altitude was a sufficient total dose of hypoxia to increase both Hbmass and VO2max [ABSTRACT FROM AUTHOR]

Japanese police conduct highly sensitive and quick blood tests to detect human hemoglobin (Hb), because bloodstains left at a crime scene have probative value of circumstantial evidence in a criminal investigation. Although DNA detection from a bloodstain is a useful tool to identify an individual, doing so requires evidence that the bloodstain is of human origin. Stimulant drug abuse and dependence causes major social problems and crimes in Japan, and bloodstains are often found inside syringes seized from drug abusers. In this case, Hb often cannot be detected by conventional testing as high concentrations of stimulants, such as methamphetamine hydrochloride (MA), in blood trigger polymerization of Hb molecules, which become insoluble under non-reducing conditions and can no longer be detected by immunochromatographic detection kits. To overcome this problem, we analyzed methods to detect denatured Hb from bloodstains contaminated with MA. Reduction of polymerized Hb with a strong denaturing agent was required to solubilize polymers into monomers, suggesting that Hb aggregation is caused by aberrant formation of disulfide bonds. Based on these results, we established a pretreatment method, called Fukui's Reduction and Eiken's Dilution (FRED), that enables highly sensitive detection of human Hb from bloodstains mixed with MA by reducing and refolding of denatured Hb. This powerful method can be applied to blood that has been boiled or has otherwise deteriorated for over 20 years. [ABSTRACT FROM AUTHOR]

Aims: Creatinine‐based estimated glomerular filtration rate (eGFRcre) has been shown to overestimate the glomerular filtration rate (GFR) when it is compared with cystatin C‐based estimated GFR (eGFRcys) in older people. We investigated clinical determinants of GFR overestimation by eGFRcre and developed a score for prediction of GFR overestimation (OE) in heart failure patients. Methods: We retrospectively examined 244 Japanese heart failure patients (aged 72.2 ± 13.1 years; 48% women) who had no known extrarenal factors that affect serum cystatin C concentration. eGFR OE by eGFRcre was defined as eGFRcre being ≥120% of cystatin C‐based eGFR. Results: The proportion of heart failure patients with OE was 14.3%. Patients with OE were older, had lower body weight and total skeletal muscle mass than those in patients without OE. Laboratory examinations showed that hemoglobin concentration was lower, and the ratio of blood urea nitrogen‐to‐creatinine was higher in patients with OE than in patients without OE. In multivariate regression analysis, body weight (<63.0 kg in men and <42.0 kg in women), hemoglobin level (<12.4 g/dL in men and <11.0 g/dL in women) and ratio of blood urea nitrogen‐to‐creatinine (>26.5) in addition to skeletal muscle mass were independently associated with OE. A score calculated by using cut‐off levels of body weight, hemoglobin concentration and ratio of blood urea nitrogen‐to‐creatinine predicted OE with a sensitivity of 97.1% and a specificity of 98.1%. Conclusion: Overestimation of GFR by eGFRcre is predictable by a novel scoring system, which might be useful for the detection of patients who require cystatin C‐based eGFR measurement for accurate assessment of renal function. Geriatr Gerontol Int 2020; 20: 752–758. [ABSTRACT FROM AUTHOR]

Aims/Introduction: We examined the association between hemoglobin A1c (HbA1c) and anemia, which was categorized into three groups according to mean corpuscular volume (MCV), as well as the association between hemoglobin in the non‐anemic range and HbA1c. Materials and Methods: We used the 2016 health checkup data from 36,422 workers without diabetes. Anemic people were divided into three groups based on MCV: <80, 80–90 and >90 fL. Non‐anemic people were divided into four groups based on their hemoglobin levels. We carried out multiple linear regression models to estimate the means and 95% confidence intervals (CIs) of HbA1c. Results: For men, 0.2% had anemia with MCV <80 fL, 0.5% had anemia with MCV 80–90 fL, 0.9% had anemia with MCV >90 fL and 98.4% had no anemia. For women, the corresponding values were 6.1, 6.4, 2.8 and 84.7%, respectively. The adjusted mean HbA1c (%) values for men with anemia with MCV <80, 80–90 and >90 fL were 5.67 (95% CI 5.60–5.74), 5.58 (95% CI 5.54–5.62) and 5.41 (95% CI 5.37–5.44), respectively. Among men without anemia, HbA1c (%) increased from 5.36 (95% CI 5.34–5.39) in those with hemoglobin ≥17.5 mg/dL to 5.45 (95% CI 5.45–5.46) in those with hemoglobin 13.0 to <14.5 mg/dL (P for trend <0.001). The HbA1c values were higher in men with anemia with MCV <80 fL or MCV 80–90 fL, but lower in men with MCV >90 fL, compared with non‐anemic men with hemoglobin 13.0 to <14.5 mg/dL (All P < 0.001). Similar findings were observed in women. Conclusions: We observed elevated HbA1c among anemic people with MCV <80 fL or MCV 80–90 fL, and decreased HbA1c among anemic people with MCV >90 fL, suggesting that different types of anemia might influence HbA1c differently. In addition, non‐anemic people with lower hemoglobin levels had higher HbA1c levels, suggesting that hemoglobin levels are in need of consideration when interpreting HbA1c values among non‐anemic people. [ABSTRACT FROM AUTHOR]

Background: A recent study revealed that whole-body vibration (WBV) tends to decrease spasticity in stroke-related hemiplegic legs. However, acute changes in cortical activation after WBV are unclear. Objective: To examine whether WBV induces acute changes in sensorimotor cortical activation in patients with stroke-related hemiplegic legs. Methods: Eleven stroke patients (mean age 52.6 [SD 15.4] years; median time after stroke 3 [25th and 75th percentiles; 3 and 10.5, respectively] months) participated in a comparative before-and-after intervention trial. Six healthy adults were also studied. WBV at 30 Hz was applied for 5 min to the hamstrings, gastrocnemius, and soleus muscles. Spasticity was assessed according to the modified Ashworth scale (MAS). Active and passive range of motion (A-ROM and P-ROM, respectively) were also measured. Change in Oxy-Hb concentration in bilateral sensorimotor cortex associated with voluntary ankle dorsiflexion of the affected limb was assessed via functional near-infrared spectroscopy (fNIRS) before and immediately after WBV. Results: MAS score, A-ROM, and P-ROM improved immediately after WBV. In the patients, while there was no significant interaction between effects of region (ipsilesional and contralesional sensorimotor cortex) and the WBV intervention (before and immediately after WBV) (F1,10 = 0.702, p =.422), there was a significant main effect of the WBV intervention (F1,10 = 6.971, p =.025). In the healthy participants, there was no association with the WBV intervention or region. Conclusions: In patients with stroke-related spastic-hemiplegic legs, WBV might result not only in clinical improvement but also in acute increase in sensorimotor cortical activation. [ABSTRACT FROM AUTHOR]

Background: Ultrafiltration during hemodialysis (HD) causes hemoconcentration. Little is known about the relationships between intra-dialytic changes in hemoglobin concentration and cardiovascular events. Thus, this study aimed to elucidate the relationships between intra-dialytic changes in hemoglobin concentration and cardiovascular events among HD patients.Methods: This prospective cohort study was based on the Japanese Dialysis Outcomes and Practice Pattern Study phases 4 and 5. The predictor was the ratio of post-dialysis hemoglobin concentration to pre-dialysis hemoglobin concentration (post-Hb/pre-Hb) at baseline. The primary outcome was major adverse cardiovascular events (MACEs). Hazard ratios (HRs) were estimated using a Cox model for the association between post-Hb/pre-Hb and MACEs, adjusting for potential confounders.Results: A total of 865 patients were enrolled. During a median follow-up of 2.6 years, 145 (16.8%) patients developed MACEs. Patients were divided into 4 categories according to baseline post-Hb/pre-Hb (<1.0, ≥1.0 to <1.1, ≥1.1 to <1.2, and ≥1.2). The multivariable-adjusted HRs for MACEs were 1.69 (95% CI 1.36-2.10), 1.29 (95% CI 1.10-1.51), and 1.31 (95% CI 1.02-1.68) in patients with post-Hb/pre-Hb ratios of <1.0, ≥1.0 to <1.1, and ≥1.2, respectively, compared with the reference post-Hb/pre-Hb ratio of ≥1.1 to <1.2. Cubic spline analyses revealed a U-shaped association between post-Hb/pre-Hb and MACEs.Conclusion: High and low intra-dialytic changes in hemoglobin concentration are associated with a high risk of MACEs in patients undergoing HD. [ABSTRACT FROM AUTHOR]

Objective: Associations between the overall quality of Japanese diets and metabolic risk factors are largely unknown. This cross-sectional study investigated this issue using data from the 2012 National Health and Nutrition Survey, Japan. Methods: Dietary intake was assessed by a 1-day weighed dietary record in 15,618 Japanese adults aged ≥ 20 years. Overall diet quality was assessed by adherence to the Japanese Food Guide Spinning Top (JFG score), its modified version (modified JFG score), the Mediterranean diet score (MDS) and the Dietary Approaches to Stop Hypertension (DASH) score. Metabolic risk factors included BMI, waist circumference, blood pressure, total, HDL- and LDL-cholesterol and glycated haemoglobin. Results: While DASH score was consistently associated with favourable nutrient intake patterns (including higher micronutrient and dietary fibre intakes and lower SFA and sodium intakes), other scores were associated with both favourable and unfavourable aspects (e.g., lower micronutrient intakes for JFG score, higher SFA intakes for modified JFG score and higher sodium intakes for MDS). The associations with metabolic risk factors were also inconsistent and unexpected, including positive associations of JFG and modified JFG scores with LDL-cholesterol, inverse associations of MDS with HDL-cholesterol and null associations of DASH score with blood pressure. Conclusions: This study did not show expected and consistent associations of the four available diet quality scores with nutrient intakes and metabolic risk factors in Japanese adults. This in turn suggests the need for a scientific base on which to develop an appropriate tool for assessing the quality of diets in the Japanese context. [ABSTRACT FROM AUTHOR]

Little is known about the association between glycemic status and herpes zoster. The aim of this study was to evaluate whether glycemic status, including both high and low hemoglobin A1c(HbA1c), is associated with subsequent herpes zoster. We conducted a retrospective longitudinal study in a large teaching hospital in Tokyo, Japan, from 2005 to 2016. We included all participants who underwent voluntary health check-ups at the hospital. Our primary outcome was the incidence of herpes zoster in groups of individuals stratified by HbA1c levels, which were compared using the generalized estimating equation (GEE), adjusting for participants' demographic characteristics, social history, body mass index, and comorbidities. A total of 81,466 participants were included in this study. The mean age (standard deviation) was 46.5 (12.1), and 39,643 (48.7%) participants were male. Among them, 1751 (2.1%) were diagnosed with diabetes prior to their first visits. After a median follow-up of 1784 [interquartile range (IQR), 749–3150] days, 673 (0.8%) participants developed herpes zoster. The incidence of herpes zoster was 1.45 per 1000 person-years. Compared with the reference group (HbA1c of 5.0–6.4%), the lowest HbA1c group (HbA1c of < 5.0%) had a significantly higher adjusted odds ratio (OR) (OR 1.63; 95% confidence interval (CI), 1.07–2.48) of developing herpes zoster. The group with an HbA1c of ≥ 9.5% had a higher but nonsignificant OR than the reference group (OR 2.15; 95% CI, 0.67–6.94). Our longitudinal study demonstrated that individuals in the lowest (< 5.0%) HbA1c group had a significantly higher risk of developing herpes zoster than the reference group (HbA1c of 5.0–6.4%) after adjusting for covariates. [ABSTRACT FROM AUTHOR]

Purpose: It is important to accurately estimate accurate vancomycin (VCM) clearance (CLvcm) for appropriate VCM dosing in the treatment of patients with sepsis. However, the pathophysiology of sepsis can make CLvcm prediction less accurate. Clearance of hydrophilic antibiotics is disturbed by organ dysfunction, and hemoglobin levels are negatively correlated with sequential organ function assessment scores. We investigated whether hemoglobin levels are associated with CLvcm in sepsis patients. Methods: We performed a retrospective cohort study of patients treated with VCM in the Emergency and Critical Care Center of Nihon University Itabashi Hospital between 2005 and 2015. We enrolled 72 patients after exclusion of patients who received renal replacement therapy or surgery, had a change in hemoglobin levels more than 2 g/dL or received an erythrocyte infusion during the interval between initial VCM administration and measurement of initial trough levels, had a serum baseline creatinine level of ≥ 2 mg/dL, or were under 18 years old. Results: Enrolled patients consisted of 13 non-sepsis patients and 59 sepsis patients. In sepsis patients, although CLvcm was correlated with CrCl in HGB ≥ 9 group as well as in non-sepsis patients, its correlation was not observed in HGB < 9 group. Hemoglobin levels were correlated with CLvcm in sepsis patients but not in non-sepsis patient. Multiple linear regression analysis also indicated that lower CLvcm was associated with lower hemoglobin and CrCl. Conclusion: Lower hemoglobin levels influence a relationship between CLvcm and CrCl in sepsis patients. We propose that VCM dosing should be adjusted for hemoglobin levels in sepsis patients. [ABSTRACT FROM AUTHOR]

Background: Laboratory data in children with newly diagnosed inflammatory bowel disease (IBD) have been reported from Europe and North America, but not Asia. The aim of this study was to clarify laboratory data in Japanese children with newly diagnosed IBD, and to compare them with those in Western reports. Methods: We retrospectively reviewed patients <16 years old, newly diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) at Kurume University Hospital between January 2008 and December 2015. Results: UC and CD patients numbered 31 and 15, respectively. The percentages of patients with normal values for hemoglobin (Hb), platelet count (Plt), albumin (Alb), C‐reactive protein (CRP), and erythrocyte sedimentation rate (ESR) in the UC and CD groups were 45% and 47%; 68% and 53%; 84% and 40%; 81% and 7%; and 35% and 0%, respectively. The frequency of normal results for these five tests were similar to Western findings except for the greater frequency of normal CRP in UC. Alb and ESR differed significantly between UC and CD in both mild and moderate–severe cases. Plt, Alb, CRP, and ESR differed significantly between diseases in late‐onset IBD, whereas early onset IBD showed no differences. In UC, ESR correlated positively, while Hb and Alb correlated negatively, with disease activity. In CD, CRP and ESR correlated positively with activity. Conclusions: The proportion of Japanese children with IBD having normal values at diagnosis was mostly similar to that in Western reports. In early onset cases, UC parameters may be similar to CD. Of the five tests, ESR was particularly indicative of disease activity at diagnosis in both pediatric UC and CD. [ABSTRACT FROM AUTHOR]

Background: Serum albumin and hemoglobin levels are independently associated with subsequent cognitive deterioration in older adults. This prospective study used repeated measures analysis to identify aging trajectories in serum albumin and hemoglobin levels and investigated if these trajectories were associated with incident disabling dementia among community-dwelling older Japanese. Methods: A total of 2,005 adults aged 65–90 years participated in annual geriatric health assessments during the period from June 2002 through July 2017; the total number of observations was 9,330. A review of a municipal database of the Japanese public long-term care insurance system identified 1,999 of 2,005 adults without dementia at baseline, 278 (13.9%) of whom developed disabling dementia during the follow-up period (June 2002 through December 2017). Results: We identified three trajectory patterns (high, moderate, and low) for serum albumin and hemoglobin levels for the age period 65 through 90 years. After controlling for potential confounders, participants with moderate and low trajectories for serum albumin level had hazard ratios of 1.27 (95% confidence interval 0.94–1.72) and 2.07 (1.37–3.11), respectively, for the development of incident disabling dementia, with the high trajectory group as reference. The respective hazard ratios for hemoglobin level were 1.31 (0.93–1.85) and 1.58 (1.04–2.40), respectively. Conclusion: Dementia risk was higher for individuals with low trajectories for serum albumin and hemoglobin levels. This finding highlights the importance of interventions that improve nutritional status and control relevant diseases in middle-aged and older adults with low serum albumin and hemoglobin levels. [ABSTRACT FROM AUTHOR]

Objective: To investigate the prevalence and causes of diabetes in patients with primary aldosteronism (PA) in a multi-institutional cohort study in Japan.Research Design and Methods: The prevalence of diabetes was determined in 2,210 patients with PA (diagnosed or glycated hemoglobin [HbA1c] ≥6.5% [≥48 mmol/mol]; NGSP) and compared with that of the Japanese general population according to age and sex. In 1,386 patients with PA and clear laterality (unilateral or bilateral), the effects of plasma aldosterone concentration (PAC), hypokalemia (<3.5 mEq/L), suspected subclinical hypercortisolism (SH; serum cortisol ≥1.8 µg/dL after 1-mg dexamethasone suppression test), and PA laterality on the prevalence of diabetes or prediabetes (5.7% ≤ HbA1c <6.5% [39 mmol/mol ≤ HbA1c <48 mmol/mol]) were examined.Results: Of the 2,210 patients with PA, 477 (21.6%) had diabetes. This prevalence is higher than that in the general population (12.1%) or in 10-year cohorts aged 30-69 years. Logistic regression or χ2 test revealed a significant contribution of suspected SH to diabetes. Despite more active PA profiles (e.g., higher PAC and lower potassium concentrations) in unilateral than bilateral PA, BMI and HbA1c values were significantly higher in bilateral PA. PA laterality had no effect on the prevalence of diabetes; however, the prevalence of prediabetes was significantly higher in bilateral than unilateral PA.Conclusions: Individuals with PA have a high prevalence of diabetes, which is associated mainly with SH. The prevalence of prediabetes is greater for bilateral than unilateral PA, suggesting a unique metabolic cause of bilateral PA. [ABSTRACT FROM AUTHOR]

Background: The perinatal period is associated with a high risk of infant anemia. The aim of the present study was to determine the prevalence of infant and maternal anemia during the late lactation period and the risk factors for anemia in Japan. Methods: This retrospective cohort study was based on data from health checkups of healthy infants at 6–7 and 9–10 months of age and their mothers who visited Akitsu Children's Clinic between September 2013 and August 2015. Complete blood count data from infant blood samples obtained at 6–7 months and 9–10 months and from maternal blood samples obtained at 6–7 months, information on feeding methods, and other related parameters were analyzed. Results: Data from 388 mother–infant pairs were analyzed. The prevalence of infant anemia was 21.1% at 6–7 months and 29.1% at 9–10 months. The prevalence of anemia in exclusively breast‐fed infants was 28.4% at 6–7 months and 40.0% at 9–10 months. The risk factors for infant anemia at 9–10 months were exclusive breast‐feeding, lower gestational age at birth, male sex, and high weight gain. The prevalence of maternal anemia was 10.5%. There was no correlation between infant and maternal hemoglobin in exclusively breast‐fed infants. Conclusions: Japanese infants who were breast‐fed exclusively had a high prevalence of anemia. A nationwide strategy to prevent anemia is required to prevent infant anemia, even in a nutrition‐rich country such as Japan. [ABSTRACT FROM AUTHOR]

Introduction: We have been developing a closed-circuit cardiopulmonary bypass (CPB) system ("Dihead CPB") for application during coronary artery bypass grafting (CABG) and valve surgery. To strive for minimal hemolysis during Dihead CPB, we compared the hemolysis caused by three different suction systems and performed a clinical study with the newly applied suction system. Materials & Methods: We evaluated the hemolysis caused by roller-pump suction, the SmartSuction® Harmony® and wall suction systems with respect to suction speed and compared the systems by means of in vitro studies. A clinical study was also performed on 15 volunteers to assess hemolysis and the adequacy of the newly applied suction system with Dihead CPB. Results: Pressure inside the suction cannula was −22.5 ± 0.1 mmHg at a maximum flow of 1.5 L/min for roller-pump suction and −43.4 ± 0.1 mmHg at −150 mmHg of the set vacuum pressure of wall suction. With the SmartSuction, the pressure inside the cannula varied from −76.3 ± 1.0 to −130.3 ± 1.5 mmHg, depending on suctioning conditions. Suction speed (to suction 50 ml of blood) was fastest with the SmartSuction (69.7 ± 3.58 s) whereas, with roller suction, it was 117.3 ± 8.47 s and with wall suction 96.9 ± 7.10 s. The SmartSuction had the highest hemolysis rate (2.00 ± 0.33%) vs. 0.61 ± 0.10% for roller suction and 0.41 ± 0.11% for wall suction (p<0.001). The clinical study with wall suction showed no significant increase in plasma free hemoglobin during or after CPB compared with before surgery. Conclusions: Wall suction had less hemolysis than roller suction or the SmartSuction in the in vitro study and the clinical study with wall suction showed efficient suction speed and acceptable hemolysis, suggesting that Dihead CPB with wall suction is feasible for CABG. [ABSTRACT FROM AUTHOR]

Motivation: This study presents a novel nonlinear model which can predict 10‐year carotid ultrasound image‐based phenotypes by fusing nine traditional cardiovascular risk factors (ethnicity, gender, age, artery type, body mass index, hemoglobin A1c, hypertension, low‐density lipoprotein, and smoking) with five types of carotid automated image phenotypes (three types of carotid intima‐media thickness (IMT), wall variability, and total plaque area). Methodology: Two‐step process was adapted: First, five baseline carotid image‐based phenotypes were automatically measured using AtheroEdge™ (AtheroPoint™, CA, USA) system by two operators (novice and experienced) and an expert. Second, based on the annual progression rates of cIMT due to nine traditional cardiovascular risk factors, a novel nonlinear model was adapted for 10‐year predictions of carotid phenotypes. Results: Institute review board (IRB) approved 204 Japanese patients' left/right common carotid artery (407 ultrasound scans) was collected with a mean age of 69 ± 11 years. Age and hemoglobin were reported to have a high influence on the 10‐year carotid phenotypes. Mean correlation coefficient (CC) between 10‐year carotid image‐based phenotype and age was improved by 39.35% in males and 25.38% in females. The area under the curves for the 10‐year measurements of five phenotypes IMTave10yr, IMTmax10yr, IMTmin10yr, IMTV10yr, and TPA10yr were 0.96, 0.94, 0.90, 1.0, and 1.0. Inter‐operator variability between two operators showed significant CC (P < 0.0001). Conclusions: A nonlinear model was developed and validated by fusing nine conventional CV risk factors with current carotid image‐based phenotypes for predicting the 10‐year carotid ultrasound image‐based phenotypes which may be used risk assessment. [ABSTRACT FROM AUTHOR]

Background: Enarodustat (JTZ-951) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that mimics adaptive responses to hypoxic conditions and may provide a new therapeutic approach for managing anemia in patients with chronic kidney disease (CKD). We evaluated the efficacy, safety, and maintenance dose of enarodustat in anemic patients with CKD not on dialysis.Methods: Erythropoiesis-stimulating agent (ESA) naïve patients (correction group) and patients on a stable dose of ESA (conversion group) were randomized to receive 2, 4, or 6 mg of enarodustat or placebo once daily for 6 weeks in a double-blind manner (Period 1) followed by 24 weeks of open enarodustat treatment to maintain their hemoglobin (Hb) levels within a target range of 10.0-12.0 g/dL in reference to a dose adjustment algorithm (Period 2).Results: In the correction group, Hb level increase rate per week increased in a dose-response manner. The proportion of subjects in the conversion group who maintained Hb levels within ± 1.0 g/dL of baseline did not differ between each enarodustat arm and placebo arm during Period 1. Over 70% of subjects in both groups maintained Hb levels within the target range at the end of treatment in Period 2. The mean prescribed doses were 3.58 and 3.74 mg/day in the correction group and the conversion group, respectively. Enarodustat was associated with decreases in hepcidin and ferritin and increased total iron-binding capacity and was generally well tolerated.Conclusions: Enarodustat corrects and maintains Hb levels in anemic patients with CKD not on dialysis. [ABSTRACT FROM AUTHOR]

Iron-deficiency anemia (IDA) accounts for majority of anemia. Although iron replacement therapy is effective, in Japan, conventional iron formulations have disadvantages such as gastrointestinal side effects for oral formulations and issues of frequent administration for intravenous (IV) formulations. Ferric carboxymaltose (FCM), which overcomes these limitations, is widely used as an IV iron source overseas. In this multi-center, open-label, single-arm study, we investigated the safety and efficacy of FCM up to 12 weeks after the start of administration in patients with IDA caused by digestive diseases. Thirty-nine patients diagnosed with IDA based on hemoglobin and serum ferritin levels were included. Eligible subjects were administered FCM until the total calculated iron dose (1000 or 1500 mg) was achieved over intervals of at least 1 week. A single iron dose was 500 mg. In the full analysis set (n = 39), the incidence of adverse events and adverse drug reactions was 71.8 and 48.7%, respectively. All events were as expected from the safety profile of IV iron. The mean change from baseline (10.39 g/dL) to the highest observed hemoglobin level was 3.31 g/dL. These results indicate the safety and efficacy of FCM for treating IDA caused by digestive diseases in Japanese patients. [ABSTRACT FROM AUTHOR]

Aim: This study was conducted to evaluate clinical characteristics, treatment patterns, and healthcare resource use (HCRU) for patients in Japan with non-dialysis-dependent chronic kidney disease (CKD) and anaemia., Methods: This retrospective, longitudinal, epidemiological database extraction study used the JMDC Claims Database, comprising ~9.4 million unique beneficiaries. The observation period for anaemia and erythropoiesis-stimulating agent (ESA)/iron treatment was 1 January 2015 to 31 December 2018, and for HCRU and costs was 1 April 2016 to 31 March 2018. The non-dialysis-dependent CKD anaemia population, and the ESA treatment, iron treatment, and no-treatment cohorts were evaluated. Patient characteristics, treatment patterns, and outcomes were summarised descriptively., Results: The non-dialysis-dependent CKD anaemia population included 5908 patients (7.9%), with 464 patients in the ESA treatment cohort, 809 patients (13.7%) in the iron treatment cohort (13.7%), and 4405 (74.6%) patients in the no-treatment cohort. The prevalence of patients prescribed an antihypertensive, antidiabetic, and/or antihyperlipidaemic medication generally increased with increasing baseline CKD stage. Proportions of no treatment for anaemia decreased while ESA treatment increased with increasing CKD stage; ESA treatment increased with decreasing baseline haemoglobin levels. Patients in the ESA treatment cohort generally had more frequent events associated with HCRU and higher costs from HCRU-associated activities (e.g., inpatient and outpatient care, pharmacy)., Conclusion: As CKD severity increased, anaemia management changed from iron use or no treatment to ESA use; however, anaemia may be undertreated across all CKD stages. ESA-treated patients incurred greater HCRU-associated costs relative to other patients with non-dialysis-dependent CKD anaemia in Japan., (© 2023 The Authors. Nephrology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Nephrology.)

Abstract: Background: Anemia in infancy is still prevalent in developing countries. Commercial iron‐fortified complementary foods or iron drops are not available in Japan, and breast‐fed infants have a higher risk of anemia. We studied anemia screening in 10‐month‐old infants to determine whether breast‐feeding is a risk factor for anemia. Methods: Anemia screening was performed during regular health check for 10‐month‐old children at four local pediatric clinics in Shimane Prefecture, Japan. Venous blood was obtained for complete blood count. The clinical characteristics of each child were obtained via questionnaire. Anemia was defined as hemoglobin <11.0 g/dL. Children were categorized into anemia and no‐anemia groups, and univariate analysis was conducted on comparison of the clinical variables. Multivariate logistic regression analysis for anemia was performed to adjust for several clinical variables. Results: We analyzed data in 325 children. On univariate analysis, anemia was associated with breast‐feeding, monthly bodyweight gain and gestational week. On multivariate logistic regression analysis, anemia was associated with feeding type and gestational week (OR of partial breast‐feeding and formula feeding, 0.446; 95%CI: 0.208–0.957; and 0.223; 95%CI: 0.075–0.660, respectively, compared with exclusive breast‐feeding, OR, 1.0; and gestational week, OR, 0.753; 95%CI: 0583–0.972). Conclusion: Breast‐feeding is an important factor for anemia in 10‐month‐old Japanese infants. Breast‐fed infants after 6 months of age may need iron supplements or iron‐fortified complimentary foods. [ABSTRACT FROM AUTHOR]