Association between maternal blood or cord blood metal concentrations and catch-up growth in children born small for gestational age: an analysis by the Japan environment and children's study.

BACKGROUND: Catch-up growth issues among children born small for gestational age (SGA) present a substantial public health challenge. Prenatal exposure to heavy metals can cause adverse effects on birth weight. However, comprehensive studies on the accurate assessment of individual blood concentrations of heavy metals and their effect on the failure to achieve catch-up growth remain unavailable. This study aimed to evaluate the effects of uterine exposure to toxic metals cadmium, lead, and mercury and essential trace metals manganese and selenium at low concentrations on the postnatal growth of children born SGA. METHODS: Data on newborn birth size and other factors were obtained from the medical record transcripts and self-administered questionnaires of participants in the Japan Environment and Children's Study. The blood concentrations of lead, cadmium, mercury, selenium, and manganese in pregnant women in their second or third trimester were determined by inductively coupled plasma mass spectrometry. These heavy metal concentrations were also assessed in pregnant women's cord blood. Furthermore, the relationship between each heavy metal and height measure/catch-up growth in SGA children aged 4 years was analyzed using linear and logistic regression methods. These models were adjusted for confounders. RESULTS: We studied 4683 mother-child pairings from 103,060 pregnancies included in the Japan Environment and Children's Study. Of these, 278 pairs were also analyzed using cord blood. At 3 and 4 years old, 10.7% and 9.0% of children who were born below the 10th percentile of body weight had height standard deviation scores (SDSs) below 2, respectively. Cord blood cadmium concentrations were associated with the inability to catch up in growth by 3 or 4 years old and the height SDS at 3 years old. In maternal blood, only manganese was positively associated with the height SDS of SGA children aged 2 years; however, it was not significantly associated with catch-up growth in these children. CONCLUSION: Cadmium exposure is associated with failed catch-up development in SGA children. These new findings could help identify children highly at risk of failing to catch up in growth, and could motivate the elimination of heavy metal (especially cadmium) pollution to improve SGA children's growth.

Adult-onset idiopathic peripheral pulmonary artery stenosis.

BACKGROUND: Peripheral pulmonary artery stenosis (PPS) refers to stenosis of the pulmonary artery from the trunk to the peripheral arteries. Although paediatric PPS is well described, the clinical characteristics of adult-onset idiopathic PPS have not been established. Our objectives in this study were to characterise the disease profile of adult-onset PPS. METHODS: We collected data in Japanese centres. This cohort included patients who underwent pulmonary angiography (PAG) and excluded patients with chronic thromboembolic pulmonary hypertension or Takayasu arteritis. Patient backgrounds, right heart catheterisation (RHC) findings, imaging findings and treatment profiles were collected. RESULTS: 44 patients (median (interquartile range) age 39 (29-57) years; 29 females (65.9%)) with PPS were enrolled from 20 centres. In PAG, stenosis of segmental and peripheral pulmonary arteries was observed in 41 (93.2%) and 36 patients (81.8%), respectively. 35 patients (79.5%) received medications approved for pulmonary arterial hypertension (PAH) and 22 patients (50.0%) received combination therapy. 25 patients (56.8%) underwent transcatheter pulmonary angioplasty. RHC data showed improvements in both mean pulmonary arterial pressure (44 versus 40 mmHg; p<0.001) and pulmonary vascular resistance (760 versus 514 dyn·s·cm-5; p<0.001) from baseline to final follow-up. The 3-, 5- and 10-year survival rates of patients with PPS were 97.5% (95% CI 83.5-99.6%), 89.0% (95% CI 68.9-96.4%) and 67.0% (95% CI 41.4-83.3%), respectively. CONCLUSIONS: In this study, patients with adult-onset idiopathic PPS presented with segmental and peripheral pulmonary artery stenosis. Although patients had severe pulmonary hypertension at baseline, they showed a favourable treatment response to PAH drugs combined with transcatheter pulmonary angioplasty.

Initial Triple Combination Therapy Including Intravenous Prostaglandin I2 for the Treatment of Patients with Severe Pulmonary Arterial Hypertension.

Upfront combination therapy including intravenous prostaglandin I2 (PGI2-IV) is recognized as the most appropriate treatment for patients with severe pulmonary arterial hypertension (PAH). This retrospective study aimed to determine reasons why this therapy is not used for some patients with severe PAH and describe the hemodynamic and clinical prognoses of patients receiving initial combination treatment with (PGI2-IV+) or without (PGI2-IV-) PGI2-IV.Data for patients with severe PAH (World Health Organization Functional Class III/IV and mean pulmonary arterial pressure [mPAP] ≥ 40 mmHg) were extracted from the Japan Pulmonary Hypertension Registry. Overall, 73 patients were included (PGI2-IV + n = 17; PGI2-IV- n = 56). The PGI2-IV+ cohort was younger than the PGI2-IV- cohort (33.8 ± 10.6 versus 52.6 ± 18.2 years) and had higher mPAP (58.1 ± 12.9 versus 51.8 ± 9.0 mmHg), greater prevalence of idiopathic PAH (88% versus 32%), and less prevalence of connective tissue disease-associated PAH (0% versus 29%). Hemodynamic measures, including mPAP, showed improvement in both cohorts (post-treatment median [interquartile range] 38.5 [17.0-40.0] for the PGI2-IV + cohort and 33.0 [25.0-43.0] mmHg for the PGI2-IV - cohort). Deaths (8/56) and lung transplantation (1/56) occurred only in the PGI2-IV - cohort.These Japanese registry data indicate that older age, lower mPAP, and non-idiopathic PAH may influence clinicians against using upfront combination therapy including PGI2-IV for patients with severe PAH. Early combination therapy including PGI2-IV was associated with improved hemodynamics from baseline, but interpretation is limited by the small sample size.

Study Design and Participants' Profile in the Sub-Cohort Study in the Japan Environment and Children's Study (JECS).

BACKGROUND: The Japan Environment and Children's Study (JECS) is a nationwide birth cohort study investigating environmental effects on children's health and development. A Sub-Cohort Study has begun, conducting extended exposure and outcome measurements by targeting a subgroup randomly selected from the JECS Main Study. We report the Sub-Cohort Study methodology and participants' baseline profiles. METHODS: Of 100,148 children in the JECS Main Study, children born after April 1, 2013 who met eligibility criteria ([1] all questionnaire and medical record data from children and their mothers collected from the first trimester to 6 months of age, [2] biospecimens [except umbilical cord blood] from children and their mothers collected at first to second/third trimester and delivery) were randomly selected for each Regional Centre at regular intervals. Face-to-face assessment of neuropsychiatric development, body measurement, paediatrician's examination, blood/urine collection for clinical testing and chemical analysis, and home visits (ambient and indoor air measurement and dust collection) are conducted. Participants are followed up at 1.5 and 3 years old for home visits, and 2, 4, 6, and 8 years old for developmental/medical examination. The details of protocols after age 10 are under discussion. RESULTS: Of 10,302 selected children, 5,017 participated. The profiles of the participating mothers, fathers and children did not substantially differ between the Main Study and Sub-Cohort Study. CONCLUSION: The JECS Sub-Cohort Study offers a platform for investigating associations between environmental exposure and outcomes.

Mixed venous oxygen tension is a crucial prognostic factor in pulmonary hypertension: a retrospective cohort study.

BACKGROUND: The prognostic value of mixed venous oxygen tension (PvO2) at pulmonary hypertension diagnosis treated with selective pulmonary vasodilators remains unclear. This study sought to investigate the association of PvO2 with long-term prognosis in pulmonary arterial hypertension (PAH) and medically treated chronic thromboembolic pulmonary hypertension (CTEPH) and to identify the distinct mechanisms influencing tissue hypoxia in patients with CTEPH or PAH. METHODS: We retrospectively analyzed data from 138 (age: 50.2 ± 16.6 years, 81.9% women) and 268 (age: 57.4 ± 13.1 years, 72.8% women) patients with PAH and CTEPH, respectively, diagnosed at our institution from 1983 to 2018. We analyzed the survival rates of patients with/without tissue hypoxia (PvO2 < 35 mmHg) and identified their prognostic factors based on the pulmonary hypertension risk stratification guidelines. RESULTS: Survival was significantly poorer in patients with tissue hypoxia than in those without it for PAH (P = 0.001) and CTEPH (P = 0.017) treated with selective pulmonary vasodilators. In patients with PAH, PvO2 more strongly correlated with prognosis than other hemodynamic prognostic factors regardless of selective pulmonary vasodilators usage. PvO2 was the only significant prognostic factor in patients with CTEPH treated with pulmonary hypertension medication. Patients with CTEPH experiencing tissue hypoxia exhibited significantly poorer survival than those in the intervention group (P < 0.001). PvO2 more strongly correlated with the cardiac index (CI) than the alveolar-arterial oxygen gradient (A-aDO2) in PAH; whereas in CTEPH, PvO2 was more strongly correlated with A-aDO2 than with CI. CONCLUSIONS: PvO2 may represent a crucial prognostic factor for pulmonary hypertension. The prognostic impact of tissue hypoxia affects different aspects of PAH and CTEPH, thereby reflecting their distinct pathogenesis.

The glutathione cycle shapes synaptic glutamate activity.

Glutamate is the most abundant excitatory neurotransmitter, present at the bulk of cortical synapses, and participating in many physiologic and pathologic processes ranging from learning and memory to stroke. The tripeptide, glutathione, is one-third glutamate and present at up to low millimolar intracellular concentrations in brain, mediating antioxidant defenses and drug detoxification. Because of the substantial amounts of brain glutathione and its rapid turnover under homeostatic control, we hypothesized that glutathione is a relevant reservoir of glutamate and could influence synaptic excitability. We find that drugs that inhibit generation of glutamate by the glutathione cycle elicit decreases in cytosolic glutamate and decreased miniature excitatory postsynaptic potential (mEPSC) frequency. In contrast, pharmacologically decreasing the biosynthesis of glutathione leads to increases in cytosolic glutamate and enhanced mEPSC frequency. The glutathione cycle can compensate for decreased excitatory neurotransmission when the glutamate-glutamine shuttle is inhibited. Glutathione may be a physiologic reservoir of glutamate neurotransmitter.

Improving visualization of the articular cartilage of the knee with magnetic resonance imaging under axial traction: a comparative study of different traction weights.

OBJECTIVE: Lesions of the articular cartilage of the knee, especially early grades, are not always accurately detected by magnetic resonance imaging (MRI) because of contact between the articular cartilage surfaces of the femur and the tibia. This study aimed to assess the effects of axial leg traction during knee MRI examination on joint space widening and articular cartilage visualization and evaluate the ideal weight for traction. METHODS: MRI was performed on ten healthy volunteers using a 3-T MRI unit with a 3D dual-echo steady-state gradient-recalled echo sequence. Conventional MRI was performed first, followed by traction MRI. The traction weight increased in the order of 5 kg, 10 kg, and 15 kg. Joint space widths were measured, and articular cartilage visualization was assessed at the medial and lateral tibiofemoral joints. Volunteers were asked to evaluate pain and discomfort using a visual analog scale during each procedure with axial traction to assess the safety of traction MRI. RESULTS: The medial tibiofemoral joint space width significantly increased, and the visualization of the articular cartilage significantly improved by applying traction. The joint space width and the articular cartilage visualization showed no significant differences among traction weights of 5 kg, 10 kg, and 15 kg. Pain and discomfort during traction MRI examination were lowest with a traction weight of 5 kg. CONCLUSION: Traction MRI examination may be useful in evaluating articular cartilage lesions at the medial tibiofemoral joint. A traction weight of 5 kg may be sufficient with minimum pain and discomfort.

Indoor air quality of 5,000 households and its determinants. Part A: Particulate matter (PM2.5 and PM10-2.5) concentrations in the Japan Environment and Children's Study.

Exposure to particulate matter (PM) is one of the important risk factors for morbidity and mortality. Although PM concentrations have been assessed using air quality monitoring stations or modelling, few studies have measured indoor PM in large-scale birth cohorts. The Japan Environment and Children's Study (JECS) measured indoor and outdoor air quality in approximately 5000 households when the participating children were aged 1.5 and 3 years. PM was collected using portable pumps for 7 days (total of 24 h), inside and outside each home. Prediction models for indoor PM concentrations were built using data collected at age 1.5 years and post-validated against data collected at age 3 years. Median indoor/outdoor PM2.5 and PM10-2.5 concentrations at age 1.5 years [3 years] were 12.9/12.7 [12.5/11.3] µg/m3 and 5.0/6.3 [5.1/6.1] µg/m3, respectively. Random forest regression analysis found that the major predictors of indoor PM2.5 were indoor PM10-2.5, outdoor PM2.5, indoor smoking, observable smoke and indoor/outdoor temperature. Indoor PM2.5, outdoor PM10-2.5, indoor humidity and opening room windows were important predictors of indoor PM10-2.5 concentrations. Indoor benzene, acetaldehyde, ozone and nitrogen dioxide concentrations were also found to predict indoor PM2.5 and PM10-2.5 concentrations, possibly due to the formation of secondary organic aerosols. These findings demonstrate the importance of reducing outdoor PM concentrations, avoiding indoor smoking, using air cleaner in applicable and diminishing sources of VOCs that could form secondary organic aerosols, and the resulting models can be used to predict indoor PM concentrations for the rest of the JECS cohort.

Indoor air quality of 5,000 households and its determinants. Part B: Volatile organic compounds and inorganic gaseous pollutants in the Japan Environment and Children's study.

Volatile organic compounds (VOCs) are major indoor air pollutants. Quantification of indoor concentrations of VOCs and identification of factors associated with these concentrations can help manage indoor air quality. This study measured the concentrations of VOCs and inorganic gaseous pollutants in around 5000 households in Japan and utilised a random forest model to estimate these concentrations and identify important determinants. The homes of 5017 randomly selected participants in the Japan Environment and Children's Study (JECS) were visited twice, when the children were aged 1.5 and 3 years. Twelve VOCs and inorganic gaseous pollutants were measured during 7 days by passive samplers. Various factors in these households, including household appliances, building characteristics, cooking styles, use of consumer products, renovation, pets, personal behaviours and ventilation were recorded. A random forest model with recursive feature elimination was utilised to identify factors predictive of VOCs and inorganic gaseous pollutants. Toluene, formaldehyde and acetaldehyde were the dominant indoor VOCs. The 95th percentiles of indoor p-dichlorobenzene concentrations at 1.5 and 3 years were 67 µg/m3 and 71 µg/m3, respectively. Random forest models with coefficients of determination ranging from 0.34 to 0.76 outperformed the traditional linear regression models. Factors associated with indoor VOC and inorganic gaseous pollutant concentrations included their outdoor concentrations, indoor and outdoor temperature and relative humidity, month of the year, hours windows were open, kerosene heater use and times of operation and building age. The results provided basic descriptions of indoor VOCs and inorganic gaseous pollutants in Japan and identified several determinants of these concentrations. These determinants should be considered to maintain indoor air quality. These results can be used in epidemiological assessments of the effects of VOCs and inorganic gaseous pollutants on health in children.

A combined stepping and visual tracking task predicts cognitive decline in older adults better than gait or visual tracking tasks alone: a prospective study.

BACKGROUND: It is unclear whether motor-cognitive dual tasks predict cognitive decline better than either motor or cognitive tasks alone. AIMS: To examine the utility of the novel motor-cognitive dual-task test [Stepping Trail Making Test (S-TMT)], as a predictor of cognitive decline, and compare its predictive performance with single motor or cognitive tests. METHODS: This 2-year population-based prospective study included 626 adults aged ≥ 70 years from Takashimadaira, Itabashi, Tokyo. The S-TMT measured the time taken to step on 16 numbers in order. Gait speed and TMT-A were assessed with standardized methods as single motor and cognitive tasks, respectively. A decline in the Mini-Mental State Examination score by ≥ 3 points over 2 years was defined as a significant cognitive decline. RESULTS: Over 2 years, 97 (15.5%) experienced cognitive decline. After adjusting for confounders, binary logistic regression models showed no significant associations between gait speed, TMT-A time tertiles, and risk of cognitive decline, but participants in the longest tertile of S-TMT time were more likely to develop cognitive decline than those of the shortest tertile (odds ratio 2.14; 95% confidence interval 1.17-3.90). Only the addition of the S-TMT time to the covariates model significantly improved the reclassification indices for predicting cognitive decline (net reclassification improvement: 0.31, P < 0.01; integrated discrimination improvement: 0.01, P = 0.02). DISCUSSION AND CONCLUSION: Only the S-TMT was significantly associated with cognitive decline and improved reclassification indices, indicating that it is more useful for predicting cognitive decline than individual gait speed or visual tracking tests alone.

[Trajectories of Dietary Variety Score among community-dwelling older Japanese and their related factors].

AIM: To categorize the age-related trajectories of dietary variety score (DVS) in the community-dwelling elderly and to examine the associated factors. METHODS: The study population included 1,195 people who underwent a medical checkup for the elderly in Kusatsu-town, Gunma Prefecture in 2012 to 2017. A multinomial logistic regression analysis was performed to examine the factors associated with the age-related trajectories of DVS. The dependent variables were sex, age, family structure, years of education, BMI, subjective chewing ability, TMIG-IC, GDS-15, MMSE, smoking, alcohol consumption, and history of hypertension, dyslipidemia, diabetes mellitus, and stroke. RESULTS: The adjusted odds ratio (95% confidence intervals) of the low trajectory group in comparison to the medium trajectory group were 2.69 (1.02-7.08) for subjective chewing ability (no chewing), 1.11 (1.06-1.17) for GDS-15, 1.76 (1.14-2.73) for current smoking, and 1.70 (1.19-2.43) for past smoking. In contrast, the adjusted odds ratio of the high trajectory group in comparison to the medium trajectory group were 0.61 (0.37-1.00) for men, 1.04 (1.01-1.07) for age, 0.58 (0.38-0.89) for subjective masticatory ability (difficult to chew), 0.88 (0.82-0.96) for GDS-15, and 0.55 (0.37-0.83) for a history of hypertension. CONCLUSIONS: The age-related trajectory patterns of DVS in the community-dwelling elderly can be categorized into three types. In order to maintain a high quality of food intake, it was shown that, in addition to subjective masticatory ability and mental health factors, such as depression, we should pay attention to the control of hypertension, which is a risk factor for lifestyle diseases, and lifestyle habits such as smoking.

Maternal intake of one-carbon metabolism-related B vitamins and anorectal malformations in the Japan Environment and Children's Study.

The occurrence of anorectal malformations (ARM) is thought to be reduced with sufficient folate intake. However, there is no apparent evidence. We focused on enzyme cofactors for one-carbon metabolism, including folate (vitamin B9), vitamin B6 and vitamin B12, and explored the association between maternal combined intake of these B vitamins and the risk of ARM. Using baseline data from a Japanese nationwide birth cohort study between 2011 and 2014, we analysed data of 89 235 women (mean age at delivery = 31·2 years) who delivered singleton live births without chromosomal anomalies. Information on dietary intake was obtained via a FFQ focused on early pregnancy and used to estimate B vitamin intake. We also collected information on the frequency of folic acid supplement use. ARM occurrence was ascertained from medical records. We identified forty-three cases of ARM diagnosed up to the first month after birth (4·8 per 10 000 live births). In terms of individual intake of the respective B vitamins, high vitamin B6 intake was non-significantly associated with reduced odds of ARM. Compared with women in the low combined B vitamin intake group, the OR of having an infant with ARM was 0·4 (95 % CI 0·2, 1·0) in the high intake group (folate ≥400 µg/d, and upper half of vitamin B6 and/or vitamin B12). In conclusion, our cohort analysis suggested an inverse association between the combined intake of one-carbon metabolism-related B vitamins in early pregnancy and ARM occurrence.

Trajectories of kidney function and associated factors among community-dwelling older Japanese: a 16-year longitudinal study.

BACKGROUND: No study has reported trajectories of kidney function in later life. This long-term prospective study attempted to classify trajectories of estimated glomerular filtration rate (eGFR) and identify factors associated with these trajectories. METHODS: We collected data from annual geriatric health checkups conducted during 2002-2017 in Kusatsu Town, Gunma Prefecture, Japan. The participants were 1990 adults aged 65-90 years (mean [SD] age, 71.0 [5.7] years; 57.0% women), and the total number of observations was 9291. Data were analyzed with a group-based semiparametric mixture model and age-adjusted univariable cumulative logit models. RESULTS: Trajectory of kidney function, as determined by eGFR, was classified as low, middle, and high (4.8%, 38.9%, and 56.3% of men, respectively, and 5.2%, 31.5%, and 63.3% of women). Among men and women in the low trajectory group, chronic kidney disease (CKD) stage worsened from stage G3a (51.8 ml/min/1.73 m2 in men and 53.6 in women) at age 65 years to stage G4 (28.0 ml/min/1.73 m2 in men and 28.5 in women) by age 85 years. A history of hypertension (men and women) and heart disease (men) were more likely in the low trajectory group than in the middle and high trajectory groups. CONCLUSIONS: About 5% of community-dwelling older adults had an eGFR < 30 later in life. Our findings suggest that those with stage G3a CKD at age 65 years should be managed intensively, to control risk factors for CKD progression.

Imatinib Dramatically Improved Pulmonary Hypertension Caused by Pulmonary Tumor Thrombotic Microangiopathy (PTTM) Associated with Metastatic Breast Cancer.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare malignancy-related respiratory complication, showing rapid progression of respiratory dysfunction and pulmonary hypertension (PH). Accumulating evidence suggests that imatinib, a platelet-derived growth factor (PDGF) receptor-tyrosine kinase inhibitor, might be effective and improve severe PH in patients with PTTM associated with gastric cancer. However, its efficacy in PTTM with breast cancer is generally believed as very limited. We experienced a rare case of PTTM associated with metastatic breast cancer, a rare case who were treated with imatinib, exhibiting significant improvement of respiratory dysfunction and PH.

Rate of oral frailty and oral hypofunction in rural community-dwelling older Japanese individuals.

OBJECTIVE: To clarify the rate of oral frailty and oral hypofunction in rural community-dwelling older adults in Japan. BACKGROUND: Recently, the oral function of Japanese older adults has been evaluated multilaterally based on two concepts: oral frailty and oral hypofunction. Oral frailty is defined as a decrease in the oral function accompanied by a decrease in mental and physical functions. Oral hypofunction is a disease where the oral function is comprehensively decreased. However, their rates have not yet been elucidated. MATERIALS AND METHODS: Oral frailty and oral hypofunction were evaluated in 679 older adults from rural areas. To investigate the differences in occurrence rates due to the evaluation methods, one of the subordinate symptoms of oral hypofunction, the reduced occlusal force, was evaluated based on both the occlusal force (main method) and the number of teeth (alternative method). RESULTS: The rate of oral frailty was 22.3% in men and 22.7% in women. The rate of oral hypofunction was 39.0% in men and 46.9% in women. The overall rate of oral hypofunction was 43.6% when the reduced occlusal force of oral hypofunction was evaluated using the main method and 46.4% when evaluated using the alternative method. The proportion of participants with decreased occlusal force, the number of present teeth, oral diadochokinesis, tongue pressure and masticatory performance increased with age in both men and women. CONCLUSION: Among rural community-dwelling older adults, the rate of oral frailty was 22.5% and that of oral hypofunction was 43.6%.

[Impact of lifestyle-related diseases and frailty on the incidence of loss of independence in Japanese community-dwelling older adults: A Longitudinal Study on Aging and Health in Kusatsu].

Objectives　This study aimed to determine risk factors for frailty and lifestyle-related diseases impacting the incidence of loss of independence among Japanese community-dwelling older adults, and to measure the magnitude of these associations.Methods　We conducted an 8.1-year prospective study involving 1,214 residents of the town of Kusatsu, aged 65 years and over, who were initially free of disability and underwent the comprehensive geriatric assessment between 2002 and 2011. Loss of independence was defined as the incidence of disability or having died before the occurrence of disability was certified by the Long-Term Care Insurance program in Japan. Risk factors for lifestyle-related diseases and health status comprised hypertension, diabetes mellitus, overweight, chronic kidney disease, current smoking, past history of stroke, heart disease and cancer, frailty, underweight, anemia, hypoalbuminemia, and cognitive decline. Frailty was defined as the presence of three or more of the following criteria: Weight loss, weakness, exhaustion, slowness, and low levels of physical activity. Prefrailty was defined as the presence of one or two of these same criteria. Cox proportional-hazard regression model was used to estimate hazard ratios (HR) and the population attributable fraction (PAF) of loss of independence.Results　During the follow-up, 475 cases, including 372 disabilities and 103 deaths, were identified as having experienced loss of independence. The multivariable HRs for the loss of independence were 1.3 to 2.2-fold higher for the presence of frailty, past history of stroke, cognitive decline, prefrailty, and smoking. The PAF of loss of independence was the greatest for prefrailty (19%), followed by frailty (12%). The PAF was relatively large for prefrailty (19%) and smoking (11%) in men, and frailty (18%), prefrailty (18%), and chronic kidney disease (11%) in women. Stratified by age category, participants aged 65-74 years having frailty and several lifestyle-related diseases showed significantly higher HRs for loss of independence and greater PAFs for prefrailty (18%), frailty (13%), and smoking (11%).Conclusions　Loss of independence among Japanese community-dwelling older adults who underwent screening examinations was largely attributed to frailty and prefrailty. Our findings suggest that the screening and the intervention for frailty and lifestyle-related diseases in the early stages of old age might be beneficial in prolonging healthy life expectancy of Japanese community-dwelling older adults.

Prognostic Value of Follow-Up Hemodynamic Variables After Initial Management in Pulmonary Arterial Hypertension.

BACKGROUND: Hemodynamic variables such as cardiac index and right atrial pressure have consistently been associated with survival in pulmonary arterial hypertension (PAH) at the time of diagnosis. Recent studies have suggested that pulmonary arterial compliance may also predict prognosis in PAH. The prognostic importance of hemodynamic values achieved after treatment initiation is less well established. METHODS: Our objective was to evaluate the prognostic importance of clinical and hemodynamic variables during follow-up, including pulmonary arterial compliance, after initial management in PAH. We evaluated incident patients with idiopathic, drug- and toxin-induced, or heritable PAH enrolled in the French pulmonary hypertension registry between 2006 and 2016 who had a follow-up right-sided heart catheterization (RHC). The primary outcome was death or lung transplantation. We used stepwise Cox regression and the Kaplan-Meier method to assess variables obtained at baseline and at first follow-up RHC. RESULTS: Of 981 patients, a primary outcome occurred in 331 patients (33.7%) over a median follow-up duration of 2.8 years (interquartile range, 1.1-4.6 years). In a multivariable model considering only baseline variables, no hemodynamic variables independently predicted prognosis. Median time to first follow-up RHC was 4.6 months (interquartile range, 3.7-7.8 months). At first follow-up RHC (n=763), New York Heart Association functional class, 6-minute walk distance, stroke volume index (SVI), and right atrial pressure were independently associated with death or lung transplantation, adjusted for age, sex, and type of PAH. Pulmonary arterial compliance did not independently predict outcomes at baseline or during follow-up. The adjusted hazard ratio for SVI was 1.28 (95% confidence interval, 1.11-1.49; P<0.01) per 10-mL/m2 decrease and for right atrial pressure was 1.05 (95% confidence interval, 1.02-1.09; P<0.01) per 1-mm Hg increase. Among patients who had 2 (n=355) or 3 (n=193) low-risk prognostic features at follow-up, including a cardiac index ≥2.5 L·min-1·m-2, 6-minute walk distance >440 m, and New York Heart Association class I or II functional class, lower SVI was still associated with higher rates of death or lung transplantation (P<0.01). CONCLUSIONS: SVI and right atrial pressure were the hemodynamic variables that were independently associated with death or lung transplantation at first follow-up RHC after initial PAH treatment. These findings suggest that the SVI could be a more appropriate treatment target than cardiac index in PAH.

French experience of balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension.

AIMS: To evaluate safety and efficacy of balloon pulmonary angioplasty (BPA) in a large cohort of patients with chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: From 2014 to 2017, 184 inoperable CTEPH patients underwent 1006 BPA sessions. Safety and efficacy during the first 21 months (initial period) were compared with those of the last 21 months (recent period). A total of 154 patients had a full evaluation after a median duration of 6.1 months. RESULTS: Overall, there was a significant improvement in New York Heart Association functional class, 6-min walk distance (mean change +45 m), and a significant decrease in mean pulmonary artery pressure (PAP) and in pulmonary vascular resistance (PVR) by 26% and 43%, respectively. The percentage decreases of mean PAP and PVR were 22% and 37% in the initial period versus 30% and 49% in the recent period, respectively (p<0.05). The main complications included lung injury, which occurred in 9.1% of 1006 sessions (13.3% in the initial period versus 5.9% in the recent period; p<0.001). Per-patient multivariate analysis revealed that baseline mean PAP and the period during which BPA procedure was performed (recent versus initial period) were the strongest factors related to the occurrence of lung injury. 3-year survival was 95.1%. CONCLUSION: This study confirms that a refined BPA strategy improves short-term symptoms, exercise capacity and haemodynamics in inoperable CTEPH patients with an acceptable risk-benefit ratio. Safety and efficacy improve over time, underscoring the unavoidable learning curve for this procedure.

Albumin and Hemoglobin Trajectories and Incident Disabling Dementia in Community-Dwelling Older Japanese.

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.