Factors associated with independent ambulation at 3 months after putaminal hemorrhage: an observational study.

[Purpose] This study was aimed at evaluating the clinical indicators for predicting ambulation at 3 months after putaminal hemorrhage. [Participants and Methods] The participants were 84 inpatients with putaminal hemorrhage. The patients' background characteristics and computed tomography findings at the time of the onset of putaminal hemorrhage were obtained from their medical records. Impaired consciousness, severity of hemiplegia, higher brain dysfunction, sensory impairment, activities of daily living, and ambulatory ability were evaluated. Logistic regression analysis was performed to identify factors associated with ambulation at 3 months, and receiver operating characteristic curve analysis was conducted to determine the predictive value of the identified factors and the optimal cut-off values. [Results] Ventricular rupture, severity of hemiplegia (determined using the 12-grade hemiplegia function test), and Functional Independence Measure cognitive score were found to be independent predictors of prognosis. Severity of hemiplegia was the strongest predictor of ambulation, with a sensitivity of 80.4% and specificity of 100% when the cut-off was set at grade 6 (the ability for coordinated movement of the extensor and flexor muscles of the hip joint). [Conclusion] The severity of hemiplegia, Functional Independence Measure cognitive score, and ventricular rupture were independently associated with ambulation in patients with putaminal hemorrhage. The ability of the hip joint movement is one of the most important factors in ambulation prognosis.

Current Situation and Causes Analysis of Cadmium Pollution in the Kakehashi River Basin.

Cadmium (Cd) pollution is a public environmental problem worthy of attention. Long-term exposure to Cd may have adverse effects on human health. Our previous study showed that urinary concentration of Cd (U-Cd) in the residents decreased when Cd-polluted paddy soil was removed. However, from 2008 to 2014, the concentration of U-Cd increased. At the same time, the concentration of urinary ß2-microglobulin (ß2-MG), which is considered to be an early sign of cadmium-induced renal dysfunction, increased continuously. To find the cause of elevated urinary cadmium (U-Cd) in residents of cadmium-contaminated areas, we measured the concentration of cadmium in the blood (B-Cd) of 29 elderly residents (15 female and 14 male) and edible rice (R-Cd), and correlations between R-Cd, B-Cd, and U-Cd were analyzed in the formerly cadmium-polluted areas (the Kakehashi River basin). In 2016, we collected blood, urine, and rice samples from each participant. The analysis showed a significant correlation between age and B-Cd, U-Cd, and ß2-MG. However, there was no significant correlation between R-Cd and U-Cd, B-Cd, or ß2-MG concentrations. Although we found a slightly higher level of Cd in rice and urine than reported in 2008, we cannot be sure that it indicates an increased Cd contamination in the Kakehashi River basin because larger studies are required for such a conclusion. The increased urinary Cd concentrations in this area may be because Cd in tissues and organs returns to blood and urine as participants age, which leads to an increasing trend.

Radiographic Evaluation and Changes in Bone Density of the Humeral Side after Reverse Total Shoulder Arthroplasty.

After artificial joint surgery, bone density may decrease around the artificial joint; thus, postoperative bone density evaluation around the artificial joint is crucial. We investigated changes in bone mineral density and performed radiographic evaluation around the stem after reverse shoulder arthroplasty (RSA) surgery in 17 males (18 shoulders) and 19 females (19 shoulders), aged >65 years, with >1-year follow-up. In total, 20 and 17 cases involved massive rotator cuff tears and rotator cuff tear arthropathy, respectively. The Comprehensive Reverse Shoulder System (Standard Ingrowth) was used for all cases and cement was used in eight patients due to bone fragility. We examined lucent lines, loosening, bone resorption, and spot welds in non-cemented cases using plain radiography and postoperative bone density changes around the stem using dual-energy X-ray absorptiometry (DEXA). Lucent lines and bone resorption occurred in 5 (13.5%) and 19 (51.4%) shoulders, respectively. No loosening occurred. Compared to stem bone density at 2 weeks postoperatively, the decrease rate was the largest in the proximal medial humerus. One-year postoperative bone density was not related to sex, age, cement use, or preoperative diagnosis. Higher preoperative bone density was better maintained postoperatively. Furthermore, 1 year post RSA, spot welds were observed in approximately 48.2% of cases at the distal medial portion of the stem coating, and bone resorption occurred in the proximal medial humerus in 43.2% of cases. Therefore, postoperative bone density is related to preoperative bone density, suggesting the importance of maintaining high preoperative bone density.

Physicians' Resilience as a Positive Effect of COVID-19.

People devoid of COVID-19 may exhibit mental health problems, such as anxiety disorders, depression, panic attack, insomnia, emotional disorder, and suicidal actions. Healthcare workers (HCWs) may also exhibit these problems. Physicians should be careful an "at-risk" population. Physicians revealed higher levels of resilience than the popular workers. Humans with stronger resilience have lower feeling of anxiety and depression. We investigated the risk to physicians from an infected environment to infected patients during the pandemic. The social and psychological support of all HCWs, particularly physicians, is significant in the fight against this pandemic. Physicians working with patients with COVID-19 should set enough time to relax, sleep, and spend time with family. Resilience in physicians facing COVID-19 can induce post-traumatic growth in the future.

The combination of the low immunohistochemical expression of peroxiredoxin 4 and perilipin 2 predicts longer survival in pancreatic ductal adenocarcinoma with peroxiredoxin 4 possibly playing a main role.

Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with poor prognosis. Therefore, indicators that can be used for the early prediction of the prognosis of PDAC are needed. Peroxiredoxin (PRDX) 4 is a secretion-type antioxidant enzyme located in the cytoplasmic endoplasmic reticulum. Recent studies have reported that it is closely related to the development and prognosis of many types of cancer. Perilipin (PLIN) 2 is a lipid droplet coating protein. The high expression of PLIN2 is known to be an indicator of some types of cancer and oxidative stress management. It is highly suggestive of the interplay between PRDX4 and PLIN2 to some degree. In this study, we collected 101 patients' clinical data and paraffin-embedded specimens with PDAC and analyzed them with immunohistochemical staining of PRDX4 and PLIN2. We found that the low expression of PRDX4 predicts longer survival and a better clinical condition in PDAC patients. Moreover, when the low expression of PRDX4 is combined with the low expression of PLIN2, the 3-year survival is significantly improved. Univariate and multivariate Cox proportional hazard analyses showed that the PRDX4 expression in PDAC was an independent prognostic factor for survival. Taken together, between PRDX4 and PLIN2, PRDX4 plays a main role in prognosis and has the potential to become a clinical prognostic indicator of PDAC.

Cadmium body burden and health effects after restoration of cadmium-polluted soils in cadmium-polluted areas in the Jinzu River basin.

BACKGROUND: Itai-itai disease is caused by environmental cadmium (Cd) pollution in the Jinzu River basin in Japan. To reduce the Cd contamination of rice, soil restoration of paddy fields was carried out. We evaluated the effect of soil restoration on the health status of residents of the former Cd-polluted area. METHODS: Participants were 1,030 men and 944 women who lived in the area of restoration of Cd-polluted rice paddies. First morning urine was collected and urinary Cd, ß2-microglobulin (ß2MG), and N-acetyl-ß-D-glucosaminidase (NAG) levels were measured. Associations among age, years of residence before and after soil restoration, and urinary Cd, ß2MG, and NAG levels were evaluated by multiple regression analysis. RESULTS: The geometric mean (interquartile range) of urinary Cd (µg/g Cr) was 1.00 (0.58-1.68) in men and 1.67 (1.02-2.91) in women. The geometric means of urinary ß2MG (µg/g Cr) and NAG (U/g Cr) were 174.6 (92.6-234.2) and 1.47 (0.72-3.14) in men, and 217.6 (115.3-28.7) and 1.48 (0.73-2.96) in women, respectively. Urinary Cd, ß2MG, and NAG were significantly positively correlated (p < 0.01 all). Age and duration of residence in the Cd-polluted area before soil restoration were independently associated with urinary Cd, ß2MG, and NAG. Among the 916 participants who had resided in the area before the soil restoration, urinary Cd concentrations were significantly higher, thus by 1.03-fold (95% CI, 1.01-1.04) in men and 1.03-fold (95% CI, 1.01-1.05) in women, when the years of residence before soil restoration by each 5-years increment. By contrast, urinary Cd concentrations were significantly lower, thus 0.97-fold (95% CI, 0.96-0.99) lower in men and 0.97-fold (95% CI, 0.95-0.99) lower in women, by each 5-year increment of residence after soil restoration. A similar association was observed for urinary ß2MG concentration, and no significant association was observed for urinary NAG levels in men or women. CONCLUSIONS: Cd exposure and associated renal tubular dysfunction in residents of a former Cd-polluted area were influenced by Cd exposure from the environment prior to soil restoration. Soil restoration in Cd-polluted areas reduced the Cd exposure of local residents.

Effect of renal tubular damage on non-cancer mortality in the general Japanese population living in cadmium non-polluted areas.

This study aimed to clarify the cause-effect relationship between renal tubular damage and non-cancer mortality in the general Japanese population. We conducted a 19-year cohort study including 1110 men and 1,03 women who lived in three cadmium-non-polluted areas in 1993 or 1994. Mortality risk ratios based on urinary ß2-microglobulin (ß2MG) and N-acetyl-ß-glucosaminidase (NAG) concentrations were estimated for specific non-cancer diseases using the Fine and Gray competing risks regression model. In men, continuous urinary NAG (+1 µg/g cre) concentrations were significantly correlated with increased mortality caused by diseases of the respiratory system (hazard ratio (HR): 1.09, 95% confidence interval (CI): 1.03-1.15). Urinary ß2MG (+100 µg/g cre) concentrations were significantly correlated with increased mortalities caused by kidney and urinary tract diseases (HR: 1.01, 95% CI: 1.00-1.03), renal diseases (HR: 1.01, 95% CI: 1.00-1.03), renal failure (HR: 1.02, 95% CI: 1.00-1.03), and external causes of mortality (HR: 1.01, 95% CI: 1.00-1.02). In women, urinary NAG (+1 µg/g cre) concentrations were significantly associated with increased mortality caused by ischemic heart diseases (HR: 1.02, 95% CI: 1.00-1.04) and kidney and urinary tract diseases (HR: 1.01, 95% CI: 1.00-1.04). Urinary ß2MG (+100 µg/g cre) concentrations were significantly correlated with increased mortality caused by cardiovascular diseases (HR: 1.01, 95%CI: 1.00-1.02), ischemic heart diseases (HR: 1.01, 95%CI: 1.00-1.02), and kidney and urinary tract diseases (HR: 1.02, 95% CI: 1.01-1.03). The present study indicates that renal tubular damage was significantly related to several non-cancer disease causes of mortality in Japan's general population living in cadmium-non-polluted areas.

Corrigendum: The effects of pemafibrate and Omega-3 fatty acid ethyl on apoB-48 in dyslipidemic patients treated with statin: A prospective, multicenter, open-label, randomized, parallel group trial in Japan (PROUD48 study).

[This corrects the article DOI: 10.3389/fcvm.2023.1094100.].

The effects of pemafibrate and omega-3 fatty acid ethyl on apoB-48 in dyslipidemic patients treated with statin: A prospective, multicenter, open-label, randomized, parallel group trial in Japan (PROUD48 study).

Background: We compared the lowering effects of pemafibrate and omega-3 fatty acid ethyl on fasting apolipoprotein (apo) B-48 (apoB-48), a marker that reflects postprandial hypertriglyceridemia, which is one of the residual risks for atherosclerotic cardiovascular disease (ASCVD) with statin treatment. Methods: This prospective, multicenter, open-label, randomized, parallel group trial was conducted at 4 medical institutions between April 2020 and May 2022. A total of 126 ambulatory patients with dyslipidemia receiving statin treatment for more than 4 weeks, aged 20-79 years with fasting triglyceride (TG) levels of ≥177 mg/dl were randomly assigned to 16-week pemafibrate 0.4 mg per day treatment group (PEMA, n = 63) or omega-3 fatty acid ethyl 4 g per day treatment group (OMEGA-3, n = 63). The primary endpoint was the percentage change in fasting apoB-48 from baseline to week 16. Results: The percentage changes in fasting apoB-48 in PEMA and OMEGA-3 were -50.8% (interquartile range -62.9 to -30.3%) and -17.5% (-38.3 to 15.3%) (P < 0.001), respectively. As the secondary endpoints, the changes in fasting apoB-48 in PEMA and OMEGA-3 were -3.10 µg/ml (-5.63 to -1.87) and -0.90 µg/ml (-2.95 to 0.65) (P < 0.001), respectively. Greater decreases with significant differences in the percentage changes in TG, remnant lipoprotein cholesterol, apoC-III, fasting plasma glucose, alanine aminotransferase, gamma-glutamyl transpeptidase, and alkaline phosphatase were observed in PEMA, compared with OMEGA-3. Greater increases with significant differences in those in high-density lipoprotein (HDL) cholesterol, apoA-I, and apoA-II were observed in PEMA, compared with OMEGA-3. PEMA showed anti-atherosclerotic lipoprotein profiles in gel-permeation high-performance liquid chromatography analyses, compared with OMEGA-3. Although adverse events occurred in 9 of 63 (14.3%) patients in PEMA and 3 of 63 (4.8%) patients in OMEGA-3, no serious adverse events associated with drug were observed in either group. Conclusions: This is the first randomized trial to compare the lowering effects of pemafibrate and omega-3 fatty acid ethyl on fasting apoB-48. We concluded that pemafibrate was superior to omega-3 fatty acid ethyl in lowering effect of fasting apoB-48. Pemafibrate is expected to reduce the residual risk for ASCVD with statin treatment. Clinical trial registration: https://rctportal.niph.go.jp/en, identifier jRCTs071200011.

Small High-Density Lipoprotein and Omega-3 Fatty Acid Intake Differentiates Japanese and Japanese-Americans: The INTERLIPID Study.

AIM: To identify the most differentiated serum lipids, especially concerning particle size and fractions, between Japanese living in Japan and Japanese-Americans in Hawaii, in the absence of possible genetic confounders, and cross-sectionally examine the associated modifiable lifestyle factors. METHODS: Overall, 1,241 (aged 40-59 years) Japanese living in Japan and Japanese-Americans in Hawaii were included. We quantified 130 serum lipid profiles (VLDL 1-5, IDL, LDL 1-6, high-density lipoprotein [HDL] 1-4, and their subfractions) using Bruker's 1H-nuclear magnetic resonance spectrometer for the primary outcome. Modifiable lifestyle factors included body mass index (BMI), physical activity, alcohol and smoking habits, and 70 nutrient parameters. We evaluated the different lipids between the groups using partial least squares-discriminant analysis and association between extracted lipids and lifestyle factors using multivariable linear regression analysis. RESULTS: Concentrations of HDL4, HDL with the smallest particle size, were lower in Japanese than in Japanese-Americans of both sexes. Higher fish-derived omega-3 fatty acid intake and lower alcohol intake were associated with lower HDL4 concentrations. A 1% higher kcal intake of total omega-3 fatty acids was associated with a 9.8-mg/dL lower HDL4. Fish-derived docosapentaenoic acid, eicosapentaenoic acid, and docosahexaenoic acid intake were inversely associated with HDL4 concentration. There was no relationship between country, sex, age, or BMI. CONCLUSIONS: Japanese and Japanese-Americans can be differentiated based on HDL4 concentration. High fish intake among the Japanese may contribute to their lower HDL4 concentration. Thus, HDL particle size may be an important clinical marker for coronary artery diseases or a fish consumption biomarker.

Prognostic factors in patients with septic disseminated intravascular coagulation treated with thrombomodulin: the effect of reduced thrombomodulin dose; a single-center, retrospective, observational study.

BACKGROUND: Human soluble recombinant thrombomodulin (TM alfa), a treatment for septic Disseminated intravascular coagulation (DIC), is recommended for patients with severe renal dysfunction in reduced doses. However, no studies have examined yet how dose reduction affects clinical efficacy. In this study, we investigated the significance of the TM alfa dose as a prognostic factor in clarifying the clinical background factors related to the clinical effect of TM alfa in patients with septic DIC. METHODS: This study involved 102 patients with septic DIC admitted to a single-center intensive care unit between April 2013 and March 2020, receiving TM alfa. The following factors were retrospectively collected from the medical records of the target patients: (1) patient background, (2) sequential organ failure assessment (SOFA) score, (3) Japanese Association for Acute Medicine DIC diagnostic criteria score, (4) DIC treatment information, (5) TM alfa dose per bodyweight (normal dose: 0.06 mg/kg or reduced dose: 0.02 mg/kg), (6) DIC resolution within 7 days after the start of TM alfa administration (DIC resolution), (7) all deaths within 30 days after the start of TM alfa administration (30-days-all-cause mortality), (8) presence or absence of new hemorrhagic side effects after the start of TM alfa administration. Multiple logistic regression analysis was used to assess factors associated with DIC resolution and 30-days-all-cause mortality. RESULTS: The SOFA score (odds ratio: 95% confidence interval, 0.76: 0.66-0.89), pneumonia (0.24: 0.08-0.75), and reduced dose administration of TM alfa (0.23: 0.08-0.66) were independent of and negatively related to the DIC resolution. For the 30-days-all-cause mortality, the SOFA score (1.66: 1.31-2.09), pneumonia (9.50: 2.49-36.25), and TM alfa dose reduction (3.52: 1.06-11.69) were independent, poor prognostic factors. We found no association between the hemorrhagic side effects and the TM alfa dose per bodyweight. CONCLUSIONS: The reduced dose of TM alfa for patients with severe renal dysfunction was observed to be an influential factor for DIC resolution and 30-day all-cause mortality, as were SOFA scores and pneumonia. Further studies are required in the future to verify this finding.

Study protocol of the PROUD48 study comparing the effects of pemafibrate and omega-3 fatty acid ethyl esters on ApoB-48 in statin-treated patients with dyslipidaemia: a prospective, multicentre, open-label, randomised, parallel group trial in Japan.

INTRODUCTION: This study will compare the lowering effects of pemafibrate and omega-3 fatty acid ethyl esters on fasting apolipoprotein B-48 (apoB-48), a surrogate marker reflecting postprandial hypertriglyceridaemia, which is a residual risk for atherosclerotic cardiovascular disease with statin treatment. METHODS AND ANALYSIS: This is a prospective, multicentre, open-label, randomised, parallel group, comparative trial. Adult Japanese patients with dyslipidaemia receiving statin treatment for more than 4 weeks with a fasting triglyceride level ≥177 mg/dL will be randomly assigned in a 1:1 ratio to receive pemafibrate (0.4 mg orally per day) or omega-3 fatty acid ethyl esters (4 g orally per day) for 16 weeks. The primary endpoint is the percentage change in fasting apoB-48 from baseline to 16 weeks. The key secondary endpoints include the change in fasting apoB-48 from baseline to 16 weeks, the percentage changes in clinical variables from baseline to 16 weeks and the incidence of adverse events. A total sample size of 128 was set by considering the increased drop-out rate due to the COVID-19 pandemic, in addition to estimation based on a two-sided alpha of 0.05 and a power of 0.8 for apoB-48. ETHICS AND DISSEMINATION: The study protocol has been approved by the Certified Review Board of the University of the Ryukyus for Clinical Research Ethics (No. CRB7200001) and will be performed in accordance with the Declaration of Helsinki. Written informed consent will be obtained from all participants. The results of the study will be disseminated through publications and conference presentations to participants, healthcare professionals and the public. TRIAL REGISTRATION NUMBER: jRCTs071200011.

Renal tubular dysfunction and cancer mortality in the Japanese general population living in cadmium-non-contaminated areas.

The relationship between cadmium exposure, exposure-related renal tubular dysfunction, and mortality have been reported, mainly in the residents of Cd-contaminated areas in Japan. The aim of this study was to establish the cause-effect relationship between renal tubular dysfunction and cancer mortality in the general population in non-contaminated areas. A 19-year cohort study was conducted in 1110 men and 1703 women in 1993 or 1994, who lived in three cadmium-non-contaminated areas. Mortality risk ratios of urinary ß2-microglobulin (ß2MG) and N-acetyl-ß-glucosaminidase (NAG) for all malignant neoplasms and specific cancers were estimated using the Fine and Gray competing risks regression model. Significant hazard ratios (HRs) for liver and pancreas cancer were observed for NAG (liver: HR corresponding to an increase of 1 IU/g cr, 1.10, 95%CI, 1.02-1.19, pancreas: HR, 1.10, 95%CI, 1.02-1.19) in men. In women, a negative HR was observed for NAG (lung cancer: HR 0.80, 95% CI, 0.67-0.96) and for ß2MG (all malignant neoplasms: HR, 0.97, 95% CI, 0.93-1.00). The present study indicated that renal tubular dysfunction was significantly related to mortality in the general population of cadmium-non-contaminated areas in Japan.

Risk Classification for Metabolic Syndrome and the Incidence of Cardiovascular Disease in Japan With Low Prevalence of Obesity: A Pooled Analysis of 10 Prospective Cohort Studies.

Background It is uncertain whether risk classification under the nationwide program on screening and lifestyle modification for metabolic syndrome captures well high-risk individuals who could benefit from lifestyle interventions. We examined the validity of risk classification by linking the incidence of cardiovascular disease (CVD). Methods and Results Individual-level data of 29 288 Japanese individuals aged 40 to 74 years without a history of CVD from 10 prospective cohort studies were used. Metabolic syndrome was defined as the presence of high abdominal obesity and/or overweight plus risk factors such as high blood pressure, high triglyceride or low high-density lipoprotein cholesterol levels, and high blood glucose levels. The risk categories for lifestyle intervention were information supply only, motivation-support intervention, and intensive support intervention. Sex- and age-specific hazard ratios and population attributable fractions of CVD, which were also further adjusted to consider non-high density lipoprotein cholesterol levels, were estimated with reference to nonobese/overweight individuals, using Cox proportional hazard regression. Since the reference category included those with risk factors, we set a supernormal group (nonobese/overweight with no risk factor) as another reference. We documented 1023 incident CVD cases (565 men and 458 women). The adjusted CVD risk was 60% to 70% higher in men and women aged 40 to 64 years receiving an intensive support intervention, and 30% higher in women aged 65 to 74 years receiving a motivation-support intervention, compared with nonobese/overweight individuals. The population attributable fractions in men and women aged 40 to 64 years receiving an intensive support intervention were 17.7% and 6.6%, respectively, while that in women aged 65 to 74 years receiving a motivation-support intervention was 9.4%. Compared with the supernormal group, nonobese/overweight individuals with risk factors had similar hazard ratios and population attributable fractions as individuals with metabolic syndrome. Conclusions Similar CVD excess and attributable risks among individuals with metabolic syndrome components in the absence and presence of obesity/overweight imply the need for lifestyle modification in both high-risk groups.

The Relationship between the Urinary Cadmium Concentration and Cause-Specific Mortality in Subjects without Severe Renal Damage: A 35-Year Follow-Up Study in a Cadmium-Polluted Area of Japan.

We evaluated the association between urinary cadmium concentration (uCd, µg/g Cr) and risk of cause-specific mortality according to urinary ß2-microglobulin (MG) concentration. Participants were 1383 male and 1700 female inhabitants of the Cd-polluted Kakehashi River basin. The uCd and ß2-MG were evaluated in a survey in 1981-1982, where those participants were followed-up over 35 years later. Among the participants with a urinary ß2-MG < 1000, the hazard ratios (HRs) (95% confidence interval) for mortality were significantly higher in those with a uCd of ≥10.0 compared with <5.0 for cardiovascular disease [HR 1.92 (1.08-3.40) for men, 1.71 (1.07-2.71) for women], pneumonia or influenza [2.10 (1.10-4.00) for men, 2.22 (1.17-4.19) for women], and digestive diseases [for men; 3.81 (1.49-9.74)]. The uCd was significantly associated with mortality from heart failure in women and digestive diseases in men, after adjustment for other causes of death using the Fine and Gray competing risk regression model. For participants with a urinary ß2-MG of ≥1000, no significant association was observed between uCd and any major cause of death. In the absence of kidney damage, Cd may increase the risk of death from cardiovascular disease, pneumonia, and digestive diseases.

The Association between Anthropometric Indices of Obesity and Chronic Kidney Disease in Middle-aged Japanese Men and Women: A Cohort Study.

Objective This study investigated associations between three indices of obesity-the body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR)-and the incidence of chronic kidney disease (CKD). Methods The employees of a company in Japan (1,725 men, 1,186 women; aged 35-55 years) had BMI, WC, and WHtR measured in health examinations. The incidence of CKD was determined at annual medical examinations over a six-year period. The hazard ratios for CKD were calculated using proportional hazard models, and the χ2 statistic was used to compare the strengths of the associations. Results The mean BMI (kg/m2), WC (cm), and WHtR were 23.6, 84.3, and 0.49 for men and 22.3, 79.7, and 0.50 for women, respectively. The incidence of CKD (/1,000 person-years) was 18.1 for men and 8.4 for women. In men, positive linear associations were observed between the BMI, WC, and WHtR and the risk of CKD, even after adjusting for the presence of metabolic abnormalities (p for trend <0.001, 0.012, and 0.023, respectively). In women, a linear association was observed only between the WHtR and CKD, not the BMI or WC (p for trend =0.042, 0.057, and 0.186). The χ2 statistics were the highest for the BMI in both men and women. Conclusion The BMI, WC, and WHtR were linearly associated with the risk of CKD independently of metabolic abnormalities in men, while the associations were weaker or not significant in women. The BMI was the most strongly associated with the incidence of CKD in both men and women.

The relationship between cadmium exposure and renal volume in inhabitants of a cadmium-polluted area of Japan.

This follow-up study was conducted over 30 years in a cadmium-polluted area of Japan. Urinary cadmium (U-Cd) concentration decreased by nearly half from 1986 to 2008 in men and women. However, it increased from 2008 to 2014 and maintained similar levels in 2016. Because renal atrophy may induce an increase in U-Cd, kidney volumes were determined using magnetic resonance imaging (MRI) scans in 2018. Based on the MRI results, we divided the participants into two groups, namely the normal group (n = 6, three men and three women) and the lesion group (n = 6, three men and three women). The level of urinary N-acetyl-ß-d-glucosaminidase/creatinine (U-NAG/Cr) in the lesion group was significantly higher than in the normal group. The level of serum alkaline phosphatase (Al-P) was positively associated with U-Cd. Age and renal cortex volumes showed significantly negative associations. However, U-Cd and renal cortex and kidney volumes showed no significant associations. These results suggest that U-NAG and serum Al-P were sensitive biomarkers to reflect renal tubular dysfunction and bone damage caused by cadmium poisoning. Individuals chronically exposed to Cd should be observed carefully, due to the increased effect of aging on renal cortex volumes.

Sodium-glucose cotransporter 2 inhibitors in type 2 diabetes patients with renal function impairment slow the annual renal function decline, in a real clinical practice.

AIMS/INTRODUCTION: The aim of this study was to elucidate whether sodium-glucose cotransporter 2 inhibitors (SGLT2is) treatment has any renoprotective effect for type 2 diabetes mellitus patients with an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2 in clinical practice. MATERIALS AND METHODS: We evaluated the annual eGFR slope in 85 type 2 diabetes mellitus patients with renal impairment, treated with SGLT2is ≥2 years. Each patient's eGFR was <60 mL/min/1.73 m2 at the start of SGLT2is therapy. The calculation of the annual change in eGFR for each patient was obtained by acquired eGFR data before and after 2 years of the initial SGLT2is administration, followed by analysis of the changes in the mean eGFR slope. RESULTS: The participants' mean age was 72.0 ± 9.4 years, and the mean eGFR was 47.1 ± 9.7 mL/min/1.73 m2 at the start of additional treatment with SGLT2is. The mean annual eGFR slope after SGLT2is administration (-0.11 ± 0.20 mL/min/1.73 m2 /year) was significantly slower than before SGLT2is administration (-2.93 ± 0.59 mL/min/1.73 m2 /year; P < 0.0001). Additionally, SGLT2is treatment slowed the annual decline of eGFR, independent of the levels of both the initial eGFR and albuminuria levels before SGLT2is therapy was started. In the patient groups who showed an annual eGFR decline of ≥3 and 1-3 mL/min/1.73 m2 , there was a significant slowing of the decline after SGLT2is therapy, compared with before the treatment (P < 0.001, respectively). CONCLUSIONS: SGLT2is administration slows the decline observed in the annual renal function in type 2 diabetes mellitus patients with eGFR of <60 mL/min/1.73 m2 in clinical practice.

Environmental cadmium exposure and noncancer mortality in a general Japanese population in cadmium nonpolluted regions.

The objective of this study was to assess the effect of environmental cadmium exposure according to urinary cadmium concentration (U-Cd) on noncancer mortality in a general Japanese population. We conducted a longitudinal study for 19 years in 2804 inhabitants (1107 men and 1697 women) in some cadmium nonpolluted regions in Japan. The participants were classified into quartiles based on U-Cd (µg/g cre) adjusted for urinary creatinine. Hazard ratio (HR) and 95% confidence interval (95% CI) for continuous U-Cd or the quartiles of U-Cd were calculated for noncancer mortality. By applying a Fine and Gray competing risk model, continuous U-Cd (+1 µg/g cre) showed significant HR for cardiocerebrovascular diseases (HR 1.05, 95% CI: 1.00-1.11), cerebrovascular diseases (HR 1.08, 95% CI: 1.01-1.16), and cerebral infarction (HR 1.11, 95% CI: 1.04-1.20) in men. However, notable significant HR for continuous and quartered U-Cd were not observed in women. In this study, U-Cd was associated with increased cardiocerebrovascular mortality in a general Japanese population, suggesting that environmental cadmium exposure is detrimental to the life prognosis in cadmium nonpolluted regions in Japan.

Relationship between urinary ß2 -microglobulin concentration and mortality in a cadmium-polluted area in Japan: A 35-year follow-up study.

The relationship between urinary ß2 -microglobulin (ß2 -MG) and the risk of all-cause mortality and cause-specific mortality in a cadmium (Cd)-polluted area was investigated in 3139 inhabitants (1404 men and 1735 women) of the Kakehashi River basin in Japan at 35-year follow-up. The subjects had been participants in the 1981-1982 health impact survey that assessed Cd-induced renal dysfunction, as measured by the urinary ß2 -MG concentration. Hazard ratios were calculated to assess the risk of all-cause and cause-specific mortality according to the urinary ß2 -MG concentrations. Risk ratios (RRs) were assessed using the Fine and Gray regression model to account for competing risks of cause-specific mortality. The mortality rate was significantly higher in participants with urinary ß2 -MG concentrations >1000 µg/g creatinine (Cr) for men and >300 µg/g Cr for women. In the proportional hazard model, higher urinary ß2 -MG concentrations were associated with higher risks of circulatory disease, digestive system diseases, and kidney and urinary tract diseases in men and women, and with senility for women. However, when competing risk was accounted for, the RRs were significantly higher only for kidney and urinary tract diseases in men and women (RR for each increment of 1000 µg/g Cr [95% confidence interval]: 1.02 [1.00-1.04] for men, and 1.01 [1.00-1.02] for women). The long-term prognosis of participants with renal tubular dysfunction was poor, most likely due to kidney and renal tract diseases.