Pulmonary tumor thrombotic microangiopathy due to early gastric carcinoma in a patient with no antemortem findings suggestive of primary malignancy.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare and critical malignancy-related disease characterized by acute progressive pulmonary hypertension (PH). In most cases of PTTM, the cancer can be diagnosed in advance. Identification of the primary cancer is valuable for PTTM diagnosis. Here, we present the case of a patient with PTTM due to early gastric carcinoma in whom the diagnosis of malignant cancer was not revealed until macroscopic autopsy findings. This case highlights the importance of recognizing causative occult early gastric cancer leading to PTTM in cases of acute progressive PH.

Association Between Serum GDF15 Concentration and Total Mortality in Community-Dwelling Japanese Older Populations: The Involvement of Renal Dysfunction.

BACKGROUND: Serum growth differentiation factor 15 (GDF15) is associated with age-related adverse outcomes. However, renal function has not been thoroughly evaluated in studies addressing the association between GDF15 and mortality. We aimed to clarify whether GDF15 is associated with total mortality after carefully controlling renal function markers. METHODS: We divided 1 801 community-dwelling Japanese older adults into quartiles according to their serum GDF15 concentrations. The correlation of GDF15 with renal function and inflammation markers was assessed by calculating Spearman correlation coefficients. Cumulative survival rates of the quartiles were estimated. In a Cox regression analysis adjusted for confounders, the association between GDF15 and mortality was evaluated. The discriminative capacity of GDF15 for the prediction of mortality was assessed with receiver-operating characteristic analysis. RESULTS: GDF15 was correlated with cystatin C (r = 0.394), ß2-microglobulin (r = 0.382), C-reactive protein (r = 0.124), and interleukin-6 (r = 0.166). The highest GDF15 quartile showed poor survival compared to the others. Older adults with higher GDF15 were associated with an increased mortality risk, independent of demographics and clinically relevant variables (hazard ratio [95% confidence interval]: 1.98 [1.09-3.59]). This significant association disappeared when additionally adjusted for cystatin C (1.65 [0.89-3.05]) or ß2-microglobulin (1.69 [0.91-3.12]). The ability to predict mortality was approximately comparable between GDF15 (area under the curve: 0.667), cystatin C (0.691), and ß2-microglobulin (0.715). CONCLUSIONS: Serum GDF15 is associated with total mortality in older Japanese after adjustment for major confounders. The increased mortality risk in older adults with higher GDF15 may be partly attributed to decreased renal function.

Association between sarcopenia and oral functions in community-dwelling older adults: A cross-sectional study.

BACKGROUND: Few studies have examined the state of oral function in older adults with sarcopenia. We assessed the oral functions of community-dwelling older adults with sarcopenia from multiple perspectives to clarify their potentially low oral function. METHODS: A total of 1517 (86.2%; 990 women, 527 men; mean age 76.1 ± 7.6 years) participants were included in this study. Grip strength, gait speed and skeletal muscle mass index were assessed, and sarcopenia was evaluated according to the criteria of the Asian Working Group for Sarcopenia 2019. The degree of tongue coating, oral moisture, occlusal force, tongue-lip motor function, tongue pressure, masticatory function and swallowing function were assessed. The criteria for oral hypofunction (a disease that is a combination of multiple low oral functions) were used to assess oral function. Statistical analyses were performed using Kolmogorov-Smirnov test, unpaired t-test, Mann-Whitney U test, χ2 test, and univariate and multivariable logistic regression analyses, with each oral function as the dependent variable and sarcopenia as one of the independent variables. The significance level was set at P < 0.05. RESULTS: The prevalence rates of sarcopenia and severe sarcopenia were 14.2% and 3.8%, respectively. The prevalence of oral hypofunction was 39.9%. Compared with the robust group, the sarcopenia and severe sarcopenia groups tended to have a higher frequency of the following components (all P < 0.01): low occlusal force, low tongue-lip motor function, low tongue pressure, low masticatory function, low swallowing function and oral hypofunction. Univariate logistic regression analysis showed that sarcopenia was associated with low occlusal force, low tongue-lip motor function, low tongue pressure, low masticatory function, low swallowing function and oral hypofunction. The odds ratios and 95% confidence intervals of sarcopenia for each oral function were 2.62 [2.00, 3.43], 2.21 [1.69, 2.89], 3.66 [2.79, 4.81], 3.23 [2.46, 4.25], 1.66 [1.26, 2.20] and 3.59 [2.72, 4.72], respectively. Multivariable logistic regression analysis showed that sarcopenia was associated with low occlusal force (1.63 [1.10, 2.40]), low tongue pressure (2.28 [1.65, 3.15]), low masticatory function, (1.94 [1.27, 2.97]), low swallowing function (1.64 [1.17, 2.28]) and oral hypofunction (2.17 [1.52, 3.09]). CONCLUSIONS: This study demonstrated that multiple aspects of oral function were low among community-dwelling older adults with sarcopenia. The potential decline in oral functions in older adults with sarcopenia may have been overlooked until now. This study indicates the need for dental perspectives in intervening with older adults with sarcopenia and the need to encourage them to see dental professionals.

Utility of axial magnetic resonance images for detecting meniscal ramp lesions associated with anterior cruciate ligament injuries.

Background: Ramp lesions (RLs), associated with anterior cruciate ligament (ACL) injuries, should be repaired to ensure postoperative knee stability. However, it is difficult to identify all RLs before surgery using conventional sagittal magnetic resonance (MR) images and arthroscopy from the anterior, medial, and lateral portals that are usually used during ACL reconstruction. We report the effectiveness of axial images for detecting RL. Methods: From January 2018, a total of 316 knees underwent primary ACL reconstruction with preoperative magnetic resonance imaging (MRI) examination at our hospital. Among these, 149 knees, which required meniscal suturing at the same time, were retrospectively investigated. This study evaluated 22 knees with confirmed RLs around the posterior horn of the medial meniscus. The effectiveness of the preoperative sagittal and axial MR images for detecting RL was assessed. With the MR image, a three-dimensional double-echo steady-state image with a flip angle of 25° was reconstructed into the sagittal and axial planes, respectively. Reconstructed images with 3-mm slices for sagittal slices and 1-mm slices for axial sections were used. The diagnosis was made based on the presence of RL (RL was present, RL may be present, and RL was not present) by four knee surgeons with more than 10 years of experience. Results: Approximately 53% of knee cases were diagnosed with RLs using sagittal images. Meanwhile, a diagnosis was achieved using axial images in 89% of cases. Conclusion: Axial MRI may be superior in detecting RLs.

Earlier menopause is associated with higher risk of incident frailty in community-dwelling older women in England.

BACKGROUND: Although it is well known that women have higher risk of frailty, mechanisms are not clear. Reproductive history may be related to the sex difference in frailty. METHODS: A total of 1249 community-dwelling women aged ≥60 in England were examined for associations between age at menopause and risk of developing frailty. Frailty defined by the frailty phenotype was measured at baseline and 4 years later. Age at menopause was used as a continuous variable and categorical groups: premature/early (10-45 years), normal (46-55 years), and late (56 years or older). Men with comparable conditions from the same cohort were also used as a comparison. RESULTS: Earlier age at menopause was significantly associated with higher risk of incident frailty. One year later menopause age was associated with a 3% decrease in incident frailty risk (Odds ratio [OR] = 0.97, 95%CI = 0.95-1.00, p = 0.02). Women with premature or early menopause had a significantly higher risk of developing frailty compared with those with normal menopause (OR = 1.90, 95%CI = 1.28-2.81, p = 0.001), while those with late menopause did not. In a supplementary analysis with older men, older women with premature or early menopause were more likely to develop frailty compared with older men (OR = 2.29, 95%CI = 151-3.48, p < 0.001), however, there was no significant difference between women with normal or late menopause. CONCLUSIONS: Earlier menopause was significantly associated with higher risk of developing frailty. Our findings suggest that menopause or its related factors, such as decline in estrogen after menopause, potentially play an important role in the sex difference in frailty.

Deterioration after Liver Transplantation and Transthyretin Stabilizer Administration in a Patient with ATTRv Amyloidosis with a Leu58Arg (p.Leu78Arg) TTR Variant.

We herein report a 44-year-old Japanese man with hereditary transthyretin amyloidosis (ATTRv amyloidosis) harboring the variant Leu58Arg (p.Leu78Arg) in TTR in whom we conducted an observational study with liver transplantation (LT) and transthyretin (TTR) stabilizers (tafamidis and diflunisal) for 9 years. This patient showed gradual deterioration of sensory, motor, and autonomic neuropathy symptoms after LT. Furthermore, cardiac amyloidosis gradually developed. Although the present case showed deterioration of the symptoms after disease-modifying treatments, LT might be suitable in patients with the same variant if they are young and in good condition due to a long survival after LT.

Dose-response relationships of sarcopenia parameters with incident disability and mortality in older Japanese adults.

BACKGROUND: Sarcopenia-related parameters may have differential impacts on health-related outcomes in older adults. We examined dose-response relationships of body composition, muscle strength, and physical performance with incident disability and mortality. METHODS: This prospective study included 1765 Japanese residents (862 men; 903 women) aged ≥65 years who participated in health check-ups. Outcomes were incident disability and all-cause mortality. Fat mass index (FMI) and skeletal muscle mass index (SMI), determined using segmental multi-frequency bioelectrical impedance analysis, handgrip strength (HGS), and usual gait speed (UGS) were measured. We determined multivariate-adjusted hazard ratios (HRs) for disability and mortality relative to sex-specific reference values (FMI: medians; SMI: 7.0 kg/m2 for men and 5.7 kg/m2 for women; HGS: 28 kg for men and 18 kg for women; or UGS: 1.0 m/s for both sexes). Association shapes were examined using restricted cubic splines or fractional polynomial functions. RESULTS: The median follow-up was 5.3 years; 107 (12.7%) men and 123 (14.2%) women developed disability, and 101 (11.7%) men and 56 (6.2%) women died. FMI did not impact any outcome in men and disability in women, while an FMI ≤ 7.3 kg/m2 (median) was significantly associated with higher mortality risk in women, compared with median FMI. SMI did not impact disability in either sex and mortality in women, but showed a significant inverse dose-response relationship with mortality risk in men [HRs (95% confidence intervals) of minimum and maximum values compared with the reference value: 2.18 (1.07-4.46) and 0.43 (0.20-0.93), respectively], independent of HGS and UGS. HGS and UGS showed a significant inverse dose-response relationship with disability in both sexes [HGS: 1.71 (1.00-2.91) and 0.31 (0.09-0.99), respectively, in men, 2.42 (1.18-4.96) and 0.41 (0.20-0.85), respectively, in women; UGS: 2.14 (1.23-3.74) and 0.23 (0.08-0.67), respectively, in men, 3.26 (2.07-5.14) and 0.11 (0.05-0.26), respectively, in women] and mortality in women [HGS: 6.84 (2.84-16.47) and 0.06 (0.02-0.21), respectively; UGS: 2.67 (1.14-6.27) and 0.30 (0.11-0.85), respectively], independent of body composition, but did not impact mortality in men. CONCLUSIONS: Disability risk was more dependent on muscle strength and physical performance in both sexes. Mortality risk in men was more dependent on muscle mass, and mortality risk in women was influenced by lower fat mass along with muscle strength and physical performance. Although improving muscle strength and physical performance should be the first target for health promotion, it is also necessary to pay attention to body composition to extend life expectancy in older adults.

Development of a Self-made Cement Bead Maker and Its Clinical Application for the Treatment of Periprosthetic Joint Infection.

Antibiotic-loaded acrylic cement beads have a large surface area and excellent sustained-release properties. However, there are some difficulty manufacturing reasonably sized beads and their careful handling. We developed a self-made cement bead maker using a mold of a sphere with a diameter of 8 and 10 mm with a 2-mm-diameter connecting hole. With this instrument, approximately 32 beads can be made from 40 g of bone cement. We clinically applied this technique to 11 cases of periprosthetic joint infection. There was no recurrence of infection noted. The advantages of this device were that it was possible to adjust the combination of antimicrobial agents and that the shape was uniform and easy to handle during surgery.

Association of prenatal exposure to cadmium with neurodevelopment in children at 2 years of age: The Japan Environment and Children's Study.

BACKGROUND: Prenatal cadmium exposure has been associated with adverse neurodevelopmental outcomes. However, previous findings are contradictory, and little is known about the potential modifiers of the cadmium-related neurodevelopmental risk. We investigated the associations between prenatal cadmium exposure and neurodevelopment in 2-year-old children and examined the influence of mother/child characteristics. METHODS: We recruited 3545 mother-child pairs from the Japan Environment and Children's Study. We collected maternal blood during mid/late pregnancy and cord blood at delivery, and measured cadmium concentrations using inductively coupled plasma mass spectrometry. Neurodevelopment was assessed using the Kyoto Scale of Psychological Development (KSPD), which includes cognitive-adaptive (C-A), language-social (L-S), postural-motor (P-M) and developmental quotient (DQ) domains. Associations between cadmium and KSPD scores were tested using multivariable models after controlling for confounders. RESULTS: Median levels (interquartile ranges) of cadmium in maternal and cord blood were 0.70 (0.52-0.95) and 0.04 (0.03-0.06) µg/L, respectively. Maternal blood cadmium concentrations were inversely associated with P-M scores in boys (ß = -1.4, 95% confidence interval (CI): -2.7, -0.038), DQ in children of mothers who smoked during pregnancy (ß = -2.9, 95% CI: -5.7, -0.12), P-M (ß = -5.4, 95% CI: -10, -0.67), C-A (ß = -6.1, 95% CI: -11, -1.8), L-S (ß = -9.0, 95% CI: -13, -4.8) and DQ scores (ß = -6.4, 95% CI: -9.6, -3.1) in children born to mothers with gestational diabetes. Cord blood cadmium concentrations were negatively associated with L-S scores (ß = -6.0., 95% CI: -11, -0.91) in children born to mothers with gestational diabetes. CONCLUSIONS: Prenatal cadmium exposure was negatively associated with neurodevelopment in boys, in children whose mothers smoked, and in children born to mothers with gestational diabetes. Further studies in other populations are needed to confirm our findings.

Urinary Metabolites of Organophosphate Pesticides among Pregnant Women Participating in the Japan Environment and Children's Study (JECS).

Organophosphate pesticides (OPPs) exhibit neurodevelopmental toxicity. To evaluate the effect of prenatal exposure to OPPs in the Japan Environment and Children's Study, a nationally representative birth cohort study, 4575 maternal urine samples were analysed for six OPP metabolites, i.e., dialkylphosphates (DAPs). This study aimed to investigate predictors of urinary DAPs using machine learning approaches and to assess the cumulative risk based on relative potency factors among Japanese pregnant women. The median creatinine-normalised urinary concentrations (interquartile ranges) of dimethylphosphate, dimethylthiophosphate and diethylphosphate, which had a detection rate of 50% or higher, were 3.53 (1.91-6.78), 4.09 (1.66-10.8) and 3.28 (1.88-5.98) µg/g-creatinine, respectively. Possible predictors of urinary DAP concentrations were the month of urine sampling, consumption of apple and maternal body mass index. When fenitrothion was used as an index chemical for cumulative risk assessment, 0.36% of participants exceeded the lower 95% confidence limit of the benchmark dose10.

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.

Assessment of oxygenation after balloon pulmonary angioplasty for patients with inoperable chronic thromboembolic pulmonary hypertension.

BACKGROUND: The efficacy of balloon pulmonary angioplasty (BPA) in patients with inoperable chronic thromboembolic pulmonary hypertension would be promising. However, some patients showed residual dyspnea or symptoms, despite normalized hemodynamics. We aimed to clarify the clinical impact of oxygenation parameters on BPA outcome. METHOD: Ninety-nine consecutive patients who underwent BPA from September 2011 to December 2019 were enrolled. We evaluated hemodynamics with right heart catheterization, arterial blood gas examination, New York Heart Association functional class (NYHA-FC), respiratory function tests, nocturnal oximetry, and exercise capacity (6-min walk test and cardiopulmonary exercise testing) at baseline and after BPA. RESULT: Nearly normal hemodynamics was achieved after BPA (mean pulmonary artery pressure (PAP): 37.5 ± 10.0 to 20.6 ± 4.9 mmHg, p < 0.01). Oxygenation slightly improved (partial pressure of arterial oxygen; 61.5 ± 12.3 to 67.7 ± 12.7 mmHg, p < 0.01). Exertional desaturation remained unchanged (-8.1 ± 4.8 to -7.8 ± 5.1, p = 0.59), and this was associated with residual symptom (NYHA-FC ≥ 2) after BPA (OR 0.591, 95% CI 0.416-0.840, p = 0.003) in multivariate regression analyses. Lower vital capacity (r2 = 0.03, p = 0.01), higher mean PAP (r2 = 0.08, p = 0.02), and higher minute ventilation/carbon dioxide production (VE/VCO2) slope (r2 = 0.18, p < 0.01), the marker of ventilatory inefficiency, were correlated with exertional desaturation after BPA in multivariate linear analyses. CONCLUSION: Although hemodynamics nearly normalized, oxygenation did not. Moreover, exertional desaturation remained unchanged. This might cause residual symptom after BPA. Residual pulmonary hypertension suggesting incurable arteriopathy, and higher VE/VCO2 slope suggesting ventilation-perfusion mismatch might be related to exertional desaturation. Domiciliary oxygen therapy should be continued, if necessary.

Oral frailty and gait performance in community-dwelling older adults: findings from the Takashimadaira study.

Purpose This cross-sectional study compared gait performance between community-dwelling older adults with and without accumulated deficits in oral health, defined as oral frailty.Methods A total of 1,082 individuals (439 men and 643 women; mean age, 77.1 years) from the Takashimadaira study were included in the current analysis. Based on a multifaceted oral health assessment, oral frailty was defined as having three or more of the following six components: (i) fewer teeth, (ii) low masticatory performance, (iii) low articulatory oral motor skills, (iv) low tongue pressure, (v) difficulties in eating, and (vi) swallowing. Eight gait parameters were assessed using an electronic walkway. Gait characteristics comparison between groups with and without oral frailty was performed using multiple linear regression models. Models were adjusted for age, sex, educational status, income, smoking, drinking, physical activity level, height, body mass index, comorbidities, and the presence of chronic pain.Results Oral frailty was observed in 227 (21.0%) participants. After adjusting for potential confounders, the participants with oral frailty had slower gait speed, shorter stride and step length, wider step width, and longer double support duration as well as higher variability of stride length and step length.Conclusions Oral frailty was associated with poor gait performance among community-dwelling older adults.

[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.

Difficult Diagnosis of Fungal Arthritis After Arthroscopic Anterior Cruciate Ligament Reconstruction: A Case Report.

CASE: An 18-year-old woman underwent arthroscopic anterior cruciate ligament reconstruction (ACLR) but developed recurrent knee effusion. At age 25 years, her right knee pain worsened, and radiographs revealed extensive bone loss. She was diagnosed with fungal (Candida parapsilosis) osteomyelitis by synovial fluid cultures. She underwent 2-stage surgery involving an amphotericin B-loaded cement spacer implantation and bone defect grafting. No recurrence of infection has been noted for 3 years postoperatively. CONCLUSIONS: Fungal osteomyelitis may have few signs of local infection and often remains undiagnosed until bone loss occurs. Differential diagnosis should include this disease when there is recurrent knee effusion after ACLR.

Sarcopenia: prevalence, associated factors, and the risk of mortality and disability in Japanese older adults.

BACKGROUND: There is limited evidence on sarcopenia in Asian populations. This study aimed to clarify the prevalence, associated factors, and the magnitude of association with mortality and incident disability for sarcopenia and combinations of its components among Japanese community-dwelling older adults. METHODS: We conducted a 5.8 year prospective study of 1851 Japanese residents aged 65 years or older (50.5% women; mean age 72.0 ± 5.9) who participated in health check-ups. Sarcopenia was defined according to the Asian Working Group for Sarcopenia 2019 algorithm. Appendicular lean mass index (ALMI) was measured using direct segmental multi-frequency bioelectrical impedance analysis. A Cox proportional hazards regression model was used to identify associations of sarcopenia and the combinations of its components with all-cause mortality and incident disability. RESULTS: The prevalence of sarcopenia was 11.5% (105/917) in men and 16.7% (156/934) in women. Significant sarcopenia-related factors other than ageing were hypoalbuminaemia, cognitive impairment, low activity, and recent hospitalization (all P-values <0.05) among men and cognitive impairment (P = 0.004) and depressed mood (P < 0.001) among women. Individuals with sarcopenia had higher risks of mortality [hazard ratios (95% confidence interval): 2.0 (1.2-3.5) in men and 2.3 (1.1-4.9) in women] and incident disability [1.6 (1.0-2.7) in men and 1.7 (1.1-2.7) in women]. Compared with the individuals without any sarcopenia components, those having low grip strength and/or slow gait speed without low ALMI tended to have an increased risk of disability [1.4 (1.0-2.0), P = 0.087], but not mortality [1.3 (0.8-2.2)]. We did not find increased risks of these outcomes in participants having low ALMI in the absence of low grip strength and slow gait speed [1.2 (0.8-1.9) for mortality and 0.9 (0.6-1.3) for incident disability]. CONCLUSIONS: Japanese older men and women meeting Asian criteria of sarcopenia had increased risks of all-cause mortality and disability. There were no significant increased risks of death or incident disability for both participants with muscle weakness and/or low performance without low muscle mass and those with low muscle mass with neither muscle weakness nor low performance. Further studies are needed to examine the interaction between muscle loss, muscle weakness, and low performance for adverse health-related outcomes.

Determination of Urinary Cotinine Cut-Off Concentrations for Pregnant Women in the Japan Environment and Children's Study (JECS).

Few studies have assessed the accuracy of self-reported questionnaires to determine smoking habits relative to urinary biomarkers. This study investigated urinary cotinine cut-off concentrations distinguishing active, passive and non-smokers among pregnant women who participated in the Japan Environment and Children's Study, a nationwide birth cohort study. Pregnant participants with measured urinary cotinine concentrations (UCCs) and who completed self-reported questionnaires on smoking status were included (n = 89,895). The cut-off values (COVs) for active and passive smokers were calculated by fitting mixed normal distribution functions to UCCs. The sensitivity and specificity of the questionnaires were subsequently evaluated. The median (interquartile range) UCC was 0.24 (0.083-0.96) µg/g-creatinine, with the detection rate of 89%. The COV for distinguishing active smokers from passive and non-smokers was 36.8 µg/g-creatinine. When this COV was considered to represent the true condition, the questionnaire had a sensitivity of 0.523, a specificity of 0.998, a positive predictive value (PPV) of 0.967 and a negative predictive value (NPV) of 0.957. The COV for distinguishing passive smokers from non-smokers was 0.31 µg/g-creatinine, with the questionnaire having a sensitivity of 0.222, a specificity of 0.977, a PPV of 0.868 and an NPV of 0.644. As many as 78% of passive smokers might be misclassified as non-smokers.

Number of Pregnancies and Trajectory of Frailty Index: English Longitudinal Study of Ageing.

OBJECTIVES: Women are frailer than men across different populations and age groups. However, the mechanisms are still not fully understood. One possible cause is pregnancy and motherhood. The objective of this study was to examine trajectories of Frailty Index over time according to the number of pregnancies. DESIGN: A prospective study with repeated measures over 14 years. SETTING AND PARTICIPANTS: A total of 2060 community-dwelling older women aged ≥60 years in England. METHODS: The number of pregnancies was calculated as a sum of the number of live births and the number of miscarriages, still-births, or abortions. The Frailty Index (FI) was constructed using 60 deficits and repeatedly calculated every 2 years over 14 years. Trajectories of FI according to the number of pregnancies were estimated by a mixed effects model. RESULTS: Mean FI was 0.15 at baseline. A mixed effects model adjusted for age, smoking, alcohol use, education, and wealth showed that FI increased over time. A higher number of pregnancies were significantly associated with a higher FI (estimate = 0.0047, 95% confidence interval = 0.0020, 0.0074). CONCLUSIONS AND IMPLICATIONS: The current study showed that a higher number of pregnancies were significantly associated with a higher degree of frailty at baseline and over time. Pregnancy and child rearing may explain some of the observed excess risk of frailty in women. Pregnancy-related factors, such as pregnancy loss, types of delivery, length of pregnancy, childbearing, and child rearing, should be examined in relation to frailty in future studies.

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.