Residual Coronary Risk Factors Associated With Long-Term Clinical Outcomes in Patients With Coronary Artery Disease Treated With High- vs. Low-Dose Statin Therapy　- REAL-CAD Substudy.

BACKGROUND: It remains unclear which comorbidities, other than lipid parameters, or combination of comorbidities, best predicts cardiovascular events in patients with known coronary artery disease (CAD) treated with statins. Therefore, we aimed to identify the nonlipid-related prognostic factors and risk stratification of patients with stable CAD enrolled in the REAL-CAD study.Methods and Results: Blood pressure, glucose level, and renal function were considered as risk factors in the 11,141 enrolled patients. The primary endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, and unstable angina. The secondary composite endpoint was the primary endpoint and/or coronary revascularization. A significantly worse prognosis at the primary endpoint was observed in the estimated glomerular filtration rate (eGFR) ≤60 group, and the combination of eGFR ≤60 and HbA1c ≥6.0 was the worst (hazard ratio (HR) 1.66; P<0.001). However, even in the eGFR >60 group, systolic blood pressure (SBP) ≥140 mmHg met the secondary endpoint (HR 1.33; P=0.006), and the combination of eGFR ≤60 and HbA1c ≥6.0 was also the worst at the secondary endpoint (HR 1.35; P=0.002). CONCLUSIONS: Regarding nonlipid prognostic factors contributing to the incidence of cardiovascular events in statin-treated CAD patients, renal dysfunction was the most significant, followed by poor glucose control and high SBP.

Risk factor structure of heart failure in patients with cancer after treatment with anticancer agents' assessment by big data from a Japanese electronic health record.

As the prognosis of cancer patients has been improved, comorbidity of heart failure (HF) in cancer survivors is a serious concern, especially in the aged population. This study aimed to examine the risk factors of HF development after treatment by anticancer agents, using a machine learning-based analysis of a massive dataset obtained from the electronic health record (EHR) in Japan. This retrospective, cohort study, using a dataset from 2008 to 2017 in the Diagnosis Procedure Combination (DPC) database in Japan, enrolled 140,327 patients. The structure of risk factors was determined using multivariable analysis and classification and regression tree (CART) algorithm for time-to-event data. The mean follow-up period was 1.55 years. The prevalence of HF after anticancer agent administration were 4.0%. HF was more prevalent in the older than the younger. As the presence of cardiovascular diseases and various risk factors predicted HF, CART analysis of the risk factors revealed that the risk factor structures complicatedly differed among different age groups. The highest risk combination was hypertension, diabetes mellitus, and atrial fibrillation in the group aged ≤ 64 years, and the presence of ischemic heart disease was a key in both groups aged 65-74 years and 75 ≤ years. The machine learning-based approach was able to develop complicated HF risk structures in cancer patients after anticancer agents in different age population, of which knowledge would be essential for realizing precision medicine to improve the prognosis of cancer patients.

Gestational age-related changes in cervical gland length in normal singleton pregnancies from 17 to 36 weeks of gestation.

AIM: To determine the gestational age-related changes in cervical gland length in relation to cervical length (CL) in normal singleton pregnancies. METHODS: We studied 363 women with an uncomplicated singleton pregnancy (188 nulliparous and 175 multiparous women with one or more previous transvaginal deliveries). A total of 1138 cervical gland and CLs were measured longitudinally at 17-36 weeks of gestation using transvaginal ultrasonography along the curvature from the external os to the lower uterine segment and the internal end of the cervical gland area (CGA), respectively. Gestational age-related changes in cervical gland and CLs and their relationships were analyzed using a linear mixed model. RESULTS: Cervical gland and CLs decreased in different ways with advancing gestation depending on parity, and their changes were related to each other. The CGAs in nulliparous women were longer than those in multiparous women at 17-25 weeks of gestation (p < 0.05), but with no differences thereafter. CLs in multiparous women were different from those in nulliparous women at 17-23 and 35-36 weeks (p < 0.05), but there were no differences at 24-34 weeks. The cervix did not shorten compared with the CGA throughout the observational periods in nulliparous and multiparous women. CONCLUSIONS: Shortening of the cervix indicates changes to the lower uterine segment in normal pregnancies. The cervical gland region can be a useful marker representing the true cervix beyond 25 weeks of gestation, irrespective of parity.

Serum Zinc and Selenium in Children with Inflammatory Bowel Disease: A Multicenter Study in Japan.

BACKGROUND: Reports of zinc and selenium deficiencies accompanying inflammatory bowel disease (IBD) mostly have originated from Western countries and concerned adult patients. Whether Japanese children with IBD have similar deficiencies remained unclear. AIM: We aimed to elucidate differences in serum zinc and selenium concentrations in Japanese children between types of IBD. METHODS: Children under 17 years old undergoing care at 12 Japanese pediatric centers were retrospectively enrolled between November 2016 and February 2018 to 3 groups representing Crohn's disease (CD), ulcerative colitis (UC), and normal controls (NC) with irritable bowel syndrome or no illnesses. Serum zinc and selenium were measured by atomic absorption spectrophotometry. Zinc and selenium deficiencies were defined by serum concentrations < 70 µg/dL and < 9.5 µg/dL, respectively. RESULTS: Subjects included 98 patients with CD (median age, 13 years), 118 with UC (11 years), and 43 NC (11 years). Serum zinc and selenium were significantly lower in CD (median, 64 and 12.6 µg/dL respectively) than in UC (69 and 14.6; P < 0.05 and P < 0.001) or NC (77 and 15.7; P < 0.01 and P < 0.001). Zinc deficiency was significantly more prevalent in CD (60.2%) than in NC (37.2%; P < 0.05), but not than in UC (51.7%; P = 0.22). Selenium deficiency was significantly more prevalent in CD (15.3%) than in UC (5.9%; P < 0.05) or NC (0%; P < 0.01). CONCLUSIONS: In Japanese children under 17 years old, serum zinc and selenium were significantly lower in CD than in UC or NC. Zinc and selenium should be monitored, and supplemented when deficient, in children with IBD, especially CD.

Airway hyperresponsiveness and inflammation in Japanese patients with human immunodeficiency virus 1 infection.

INTRODUCTION: Despite the growing population of long-term survivors with human immunodeficiency virus 1 (HIV) exhibiting asthma-like features worldwide, the pathogenesis underlying airway hyperresponsiveness (AHR) and airway inflammation remains unclear. We aimed to investigate AHR and airway inflammation in an HIV-infected Japanese population. METHODS: Of 94 Japanese participants, 10 HIV-infected participants with asthma were excluded from the study. We compared the characteristics of HIV-infected (n = 34) and non-HIV-infected participants (n = 50). Eosinophilic, neutrophilic, mixed (eosinophilic and neutrophilic), and paucigranulocytic airway inflammatory phenotypes were classified based on induced sputum characteristics. RESULTS: The prevalence of AHR in HIV-infected participants (32.4%) was significantly higher than that in their non-HIV-infected counterparts (10.0%) (P = 0.0213). The multivariate nominal logistic regression analysis revealed HIV as an independent risk factor for AHR. HIV-infected participants were significantly more likely to have a neutrophilic airway inflammatory phenotype than non-HIV-infected participants (P = 0.0358). Furthermore, HIV-infected participants with AHR demonstrated a significant correlation between AHR levels and the percentage of sputum neutrophils (r = -0.65, P = 0.0316). The percentage of sputum neutrophils was negatively associated with the blood CD4 cell count (r = -0.66, P = 0.0266). CONCLUSIONS: We observed the high prevalence of AHR and neutrophilic airway inflammatory phenotype in Japanese participants with stable HIV infection. Our findings provide insight into the mechanisms of AHR and may facilitate the development of novel treatment for individuals with AHR and HIV infection.

Diagnostic accuracy of serum proteinase 3 antineutrophil cytoplasmic antibodies in children with ulcerative colitis.

BACKGROUND AND AIM: Serologic markers such as myeloperoxidase (MPO) antineutrophil cytoplasmic antibodies (ANCA) (MPO-ANCA) have been used to screen patients for ulcerative colitis (UC). However, MPO-ANCA shows limited accuracy in Asians. Proteinase 3 ANCA (PR3-ANCA) has performed better at UC diagnosis in Japanese adults than MPO-ANCA. The present study aimed to evaluate usefulness of PR3-ANCA for diagnosis of UC in Japanese pediatric practice. METHODS: Patients under 17 years old undergoing assessment at 12 Japanese pediatric centers between November 2016 and February 2018 were prospectively enrolled and divided into groups with UC, Crohn's disease (CD), intestinal disease control (IC), and healthy control (HC). Serum PR3-ANCA and MPO-ANCA were analyzed using chemiluminescence enzyme immunoassay kits. RESULTS: Sera from 367 patients (148 with UC at a median age of 12 years; 120 with CD, 13 years; 56 with IC, 10.5 years; and 43 with HC, 10 years) were examined. Median PR3-ANCA values in UC (1.6 U/mL) were greater than in CD (0.2; P < 0.001), IC (0.15; P < 0.001), and HC (0.1; P < 0.001). In receiver operating characteristic curve analyses, the area under the curve for PR3-ANCA was 0.79, significantly greater than for MPO-ANCA (0.58; P < 0.001). Using a cut-off value of 0.8 U/mL determined from the receiver operating characteristic analyses, PR3-ANCA showed significantly greater sensitivity (64.9%) than MPO-ANCA (cut-off, 0.2 U/mL; sensitivity, 19.6%; P < 0.001) and good specificity (83.6%). CONCLUSIONS: In Japanese children and adolescents, PR3-ANCA performed better as a serologic marker for diagnosis of UC than MPO-ANCA. To our knowledge, this is the first report of such a comparison.

Androgen receptor expression is useful to predict the therapeutic effect in HER2-positive breast carcinoma.

PURPOSE: Although HER2-positive (HER2+) invasive breast carcinomas (BC) have a different clinical therapeutic responsiveness according to estrogen and progesterone receptor expression, the relationship with androgen receptors (AR), which are the same family of steroid hormones, is poorly understood. We investigated the relationship between AR expression in HER2 BCs and therapeutic responsiveness and prognosis in this study. METHODS: We evaluated patients with HER2 (H) + invasive BC undergoing surgery after neoadjuvant chemotherapy (± HER2-targeted therapies) from 2007-2017, classified as hormone receptor-positive (Allred score: 2-8) (luminal B: LH) and receptor-negative groups (Allred: score 0) (non-luminal: NLH). AR expression was assessed by immunostaining pre-neoadjuvant chemotherapy biopsy specimens, positive with Allred score ≥ 4. The pathological complete response, disease-free survival, and overall survival rates were compared between AR-positive and AR-negative groups. RESULTS: We classified 82 patients with HER2 + invasive BC into LH (n = 45, 54.9%) and NLH groups (n = 37, 45.1%), and AR + was observed in 43 patients (52.4%) (LH: 23, 51.1%; NLH: 20, 54.1%; p = 0.79). Quasi-pathological complete response was observed in 40 patients (48.8%) (LH: 18, 40%; NLH: 22, 59.5%; p = 0.08) overall, and in 31 AR + patients (72.1%) (LH: 15, 34.9%; NLH: 16, 37.2%), significantly higher than in the AR - group for both subgroups (p < 0.001). Regarding prognosis, disease-free survival was relatively better in the AR + group in all HER2 + BCs (p = 0.085), and overall survival was significantly better in the AR + group for NLH (p = 0.029). CONCLUSIONS: High AR expression may be a useful predictor of therapeutic effects and prognosis in both subgroups of HER2 + BCs.

Diverse histomorphology of HER2-positive breast carcinomas based on differential ER expression.

AIMS: HER2-positive (HER2+) breast carcinoma (BC) cases are often treated similarly; however, they can be classified as either luminal B (LH) or non-luminal type (NLH) BC, which have different prognoses. In this study, we investigated the clinicohistomorphological features of each HER2+ BC subgroup. METHODS AND RESULTS: We classified 166 patients with HER2+ invasive BC into LH (n = 110, 66.3%) and NLH groups (n = 56, 33.7%). We further subclassified LH into patients with carcinomas expressing high levels of hormone receptors [LH-high; Allred score, oestrogen receptor (ER) and/or progesterone receptor (PgR) 4-8, n = 89, 53.6%] or low levels (LH-low; Allred score, ER and/or PgR 2 or 3, n = 21, 12.7%) for clinicohistomorphological characterisation. Morphological review showed that NLH included a percentage of patients with comedo necrosis, while LH patients had significantly more central scarring. In terms of immune responsiveness, NLH showed significantly higher rates of tumour-infiltrating lymphocytes and healing. The LH-high and NLH groups showed distinct characteristics (by both models, P < 0.05) and the LH-low group appeared to demonstrate intermediate characteristics according to multinomial analyses using covariates reflecting tumour morphology and immune response outcomes. CONCLUSIONS: These results support the classification of HER2+ BC into two major subgroups, LH-high and NLH, based on tumour morphology and immune response; LH-high proliferates via scirrhous and/or spiculated growth with a central scar, while the primary proliferation pattern of NLH is based on in-situ carcinomas containing comedo necrosis with noticeable TILs and healing.

Association between children's sleep patterns and problematic behaviors at age 5.

BACKGROUND: Night-shift lifestyles affect children as well as adults, and are associated with sleep and behavioral problems among children. This study aimed to investigate associations among sleep patterns, individual/environmental factors, and problematic behaviors in children at age 5 years. METHODS: Data for sleep patterns, individual / environmental factors, and problematic behaviors for 8,689 5-year-old children were collected from health-checkup records. Problematic behaviors investigated were anxious behavior (being afraid, difficulty being separated from the mother), developmental behavior (violence, restlessness, rebellious behavior, restrictive diet, stereotypic play), personal habits (thumb-sucking, nail-biting, tic, masturbation), and excretory problems. The relationships between sleep patterns (bedtime, sleep duration) and the presence of these behaviors were analyzed. Individual / environmental factors that affected problematic behaviors were statistically identified using a tree-form model. RESULTS: Late bedtime and short sleep duration showed significant adverse effects on children's problematic behaviors - odds ratio (OR): 1.07, 95% confidence interval (CI): 1.03-1.11 and OR: 0.92, 95% CI: 0.87-0.97, respectively. Long television watching time, abnormality at birth, and lack of father's support also showed significant adverse effects on problematic behaviors (OR: 2.34, 95% CI: 1.87-2.94), and significantly affected late bedtime and short sleep duration. CONCLUSIONS: There were significant associations among sleep patterns, individual / environmental factors, and problematic behaviors in 5-year-old children. Improving children's sleep patterns, reducing the duration of television watching, and improving support from fathers may reduce problematic behaviors.

Malic enzyme 1 is a potential marker of combined hepatocellular cholangiocarcinoma, subtype with stem-cell features, intermediate-cell type.

AIM: Combined hepatocellular cholangiocarcinoma, subtype with stem-cell features, intermediate-cell subtype (INT) shows various histological appearances and could be misdiagnosed as intrahepatic cholangiocarcinoma (iCCA). In the present study, we aimed to identify specific histological diagnostic markers of INT. METHODS: We extracted RNA from FFPE sections of six INT, five iCCA, and five hepatocellular carcinoma (HCC) cases and compared gene expression between INT, iCCA, and HCC by microarray analysis. We then undertook immunohistochemical (IHC) staining of potential key molecules identified by microarray analysis, the conventional hepatocytic marker, hepatocyte paraffin (HepPar)-1, and the cholangiocytic markers, keratin (K) 7 and K19, on 35 INT, 25 iCCA, and 60 HCC cases. RESULTS: Microarray analysis suggested that malic enzyme 1 (ME1) was significantly upregulated in INT. Immunohistochemical analysis revealed that the positive rates of ME1 in INT, iCCA, and HCC were 77.1% (27/35), 28.0% (7/25), and 61.7% (37/60), respectively. Analysis of classification and regression trees based on IHC scores indicated that HepPar-1 could be a good candidate for discriminating HCC from the others with high sensitivity (93.3%) and high specificity (96.7%). A multiple logistic regression model and receiver operating characteristic curve analysis based on the IHC scores of ME1, K7, and K19 generated a composite score that can discriminate between INT and iCCA. Using this composite score, INT could be discriminated from iCCA with high sensitivity (88.6%) and high specificity (88.0%). CONCLUSIONS: We propose that ME1 is a useful diagnostic marker of INT when used in combination with other hepatocytic and cholangiocytic markers.

Association between Non-Lipid Residual Risk Factors and Cardiovascular Events in Patients with Stable Coronary Artery Disease Treated with Pitavastatin: An Observation from the REAL-CAD Study.

AIMS: We aimed to investigate the association between non-lipid residual risk factors and cardiovascular events in patients with stable coronary artery disease (CAD) who achieved low-density lipoprotein cholesterol (LDL-C) ＜100 mg/dL from the Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy with Pitavastatin in Coronary Artery Disease (REAL-CAD) study. METHODS: The REAL-CAD study was a prospective, multicenter, open-label trial. As a sub-study, we examined the prognostic impact of non-lipid residual risk factors, including blood pressure, glucose level, and renal function, in patients who achieved LDL-C ＜100 mg/dL at 6 months after pitavastatin therapy. Each risk factor was classified according to severity. The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, and unstable angina requiring emergency hospitalization. RESULTS: Among 8,743 patients, the mean age was 68±8.2 years, and the mean LDL-C level was 84.4±18 mg/dL. After adjusting for the effects of confounders, an estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73 m2 showed the highest risk of the primary outcome (hazard ratio [HR] 1.92; 95% confidence interval [CI] 1.45-2.53). The combination of eGFR ≤ 60 and hemoglobin A1c (HbA1c) ≥ 6.0% also showed the highest risk of all-cause death (HR, 2.42; 95% CI, 1.72-3.41). CONCLUSIONS: In patients with stable CAD treated with pitavastatin and who achieved guidelines-directed levels of LDL-C, eGFR and HbA1c were independently associated with adverse events, suggesting that renal function and glycemic control could be residual non-lipid therapeutic targets after statin therapy.

Risk factors for placenta accreta spectrum in pregnancies conceived after frozen-thawed embryo transfer in a hormone replacement cycle.

OBJECTIVE: Assisted reproductive technology (ART), especially frozen-thawed embryo transfer (FET) in a hormone replacement cycle (HRC), is a risk factor for placenta accreta spectrum (PAS). This study aimed to clarify the risk factors for PAS related to the maternal background and ART techniques in pregnancies achieved after FET in an HRC. STUDY DESIGN: We performed a case-control study in two tertiary perinatal centres in Japan. Among 14,028 patients who delivered at ≥24 weeks of gestation or were transferred after delivery to two tertiary perinatal centres between 2010 and 2021, 972 conceived with ART and 13,056 conceived without ART. PAS was diagnosed on the basis of the FIGO classification for the clinical diagnosis of PAS or retained products of conception after delivery at ≥24 weeks of gestation. We excluded women with fresh embryo transfer, FET with a spontaneous ovulatory cycle, a donor oocyte cycle, and missing details of the ART treatment. Finally, among women who conceived after FET in an HRC, 62 with PAS and 340 without PAS were included in this study. Multivariate logistic regression models were used for case-control comparisons, with adjustment for maternal age at delivery, parity, endometriosis or adenomyosis, the number of previous uterine surgeries of caesarean section, myomectomy, endometrial polypectomy or endometrial curettage, placenta previa, the stage of transferred embryos, and endometrial thickness at the initiation of progestin administration. RESULTS: PAS was associated with ≥2 previous uterine surgeries (adjusted odds ratio, 3.57; 95 % confidence interval, 1.60-7.97) and the stage of embryo transfer (blastocysts: adjusted odds ratio, 2.89; 95 % confidence interval, 1.15-7.26). In patients with <2 previous uterine surgeries, PAS was associated with an endometrial thickness of <7.0 mm (adjusted odds ratio, 5.18; 95 % confidence interval, 1.10-24.44). CONCLUSION: Multiple uterine surgeries and the transfer of blastocysts are risk factors for PAS in pregnancies conceived after FET in an HRC. In women with <2 previous uterine surgeries, a thin endometrium before FET is also a risk factor for PAS in these pregnancies.

Related Factors for Abnormal Umbilical Cord Insertion: A Preliminary Study Based on Two Regional Tertiary Hospitals in Japan.

OBJECTIVE: We elucidated maternal background, perinatal complications and outcomes as potential related factors for abnormal umbilical cord insertion (ACI) -velamentous and marginal- based on data from two tertiary perinatal hospitals in Japan. MATERIALS AND METHODS: The subjects were 3,741 women with singleton pregnancies who delivered at ≥ 22 weeks' gestation in Kurume University Hospital and St. Mary's Hospital, Kurume, Japan from January 2013 to December 2015. They were divided into two groups, with and without ACI. Related factors were extracted from the medical registry database of the perinatal committee in the Japan Society of Obstetrics and Gynecology. Random Forest and stepwise logistic regression models were employed to evaluate their impact on ACI. RESULTS: Related factors for ACI in terms of maternal background and perinatal complications and outcomes were: pre-pregnancy smoking habit (adjusted odds ratio, OR, 3.38; 95% confidence interval, CI, 2.20-5.20; P < 0.0001); conception using assisted reproductive technology (adjusted OR, 2.00; 95% CI, 1.11-3.60; P = 0.021); placenta previa (adjusted OR, 4.74; 95% CI, 2.06-10.90; P < 0.0001); fetal growth restriction (adjusted OR, 2.43; 95% CI, 1.49-3.97; P < 0.0001); and non-reassuring fetal status during labor (adjusted OR, 2.74; 95% CI, 1.71-4.38; P < 0.0001). CONCLUSION: This was a preliminary study attempting to elucidate related factors for ACI in a Japanese population. However, further large-scale studies are needed in Japan.

Dynamics in the expression of programmed death ligand 1 and cluster of differentiation 163 in the tumor microenvironment of uterine cervical cancer: a single-center retrospective study.

BACKGROUND: Radiotherapy (RT) destroys cancer cells and activates the immune system while suppressing the immunity of tumor-associated tissues, including the tumor microenvironment (TME). However, to date, no anti-tumor therapeutic strategy that uses these immune mechanisms has been established. This study investigated changes in the immunity of the TME during standard radical RT for cervical cancer combined with external beam RT and brachytherapy and determined whether these changes affect prognosis. METHODS: Twenty-six patients who had completed radical RT for cervical cancer were categorized into the following two groups according to whether the cancer recurred and/or metastasized within 2 years after the start of treatment: treatment failure (n = 14) and treatment success (n = 12). We assessed the expression of programmed death 1, programmed death ligand 1 (PD-L1), cluster of differentiation (CD) 8, CD68, CD163, Forkhead box protein P3, and hypoxia-inducible factor-1α in the TME of cervical tissues collected periodically during treatment and evaluated the difference in expression rates of each marker between the success and failure groups and assessed its effect on prognosis. RESULTS: The expression levels of PD-L1 and CD163 in the TME in the treatment success group were lower than those in the treatment failure group at the midpoint during brachytherapy (p < 0.01 and p = 0.08, respectively), and the 2-year progression-free-survival (PFS) rate depended on the expression levels of PD-L1 and CD163 (p = 0.04 and p = 0.02, respectively). CONCLUSIONS: The expression rates of CD163 and PD-L1 in the TME during brachytherapy were related to treatment response and the 2-year PFS. This study may increase our understanding of tumor-associated immunity in the TME and aid in the development of therapies targeting PD-L1 or M2 macrophages in the TME in conjunction with RT, especially brachytherapy, for cervical cancer patients.

Correlation Between Work Motivation and Life Events in Female Physicians.

This study interviewed 39 mother-doctors from two university hospitals in Japan to investigate how certain stages in their lives influenced their working motivation. We conceptualized a Motivational Drive Chart to track changes of work motivation from enrollment in medical courses to the present day, recording changes in motivational values, age, and life events. It was found that the average value of motivation increased from the beginning of medical school enrollment until graduation; however, a sudden drop was noted in the age group 25 to 29 due to childcare and work-life conflicts. Motivational values were found to gradually increase in the 30 to 34 age group, owing to professional accomplishments, such as obtaining a specialist license. In Japanese society, social roles have traditionally been divided between men and women. The present study found that Japanese female doctors faced a decrease in work motivation during childrearing stages. The finding suggests that new avenues should be explored to support mother-doctors.

Combination of Prednisolone and Calcineurin Inhibitors Prevents Lung Function Decline in Patients with Anti-aminoacyl-tRNA Synthetase Antibody-Positive Polymyositis/Dermatomyositis.

OBJECTIVE: Anti-aminoacyl-tRNA synthetase antibody-positive polymyositis/dermatomyositis-associ ated interstitial lung disease (ARS-ILD) has a good prognosis, with few cases progressing to respiratory failure. This study aimed to determine factors predictive of lung function changes in patients with ARS-ILD. METHODS: We retrospectively studied 49 patients with ARS-ILD treated at Kurume University Hospital Hospital between 2000 and 2018. We followed 30 patients for more than 2 years after prednisolone (PSL) therapy, with or without calcineurin inhibitors (CNIs), evaluating clinical, physiological, computed tomography, pulmonary func tion, and serological data. RESULTS: After treatment for 24 months, no significant differences were noted between clinical parameters and improvement in forced vital capacity (FVC), %FVC, % carbon monoxide diffusing capacity/alveolar volume (%DLCO), and %DLCO/alveolar volume. Conversely, the annual change of %FVC significantly correlated with the Medical Research Council dyspnea scale grade and %FVC at the first visit and treatment. Furthermore, the annual change of %DLCO/VA significantly correlated with the duration from the first visit to treatment initiation. CONCLUSION: Compared with PSL monotherapy, combining PSL and CNI showed greater mitigation of %FVC decline. The time from onset of ARS-ILD to the first visit is critical for preventing a decline in lung function, and as such, patients should be monitored carefully.

Evaluation of the effectiveness of the physician education program on primary palliative care in heart failure.

Major cardiology societies' guidelines support integrating palliative care into heart failure (HF) care. This study aimed to identify the effectiveness of the HEart failure Palliative care Training program for comprehensive care providers (HEPT), a physician education program on primary palliative care in HF. We performed a pre- and post-test survey to evaluate HEPT outcomes. Physician-reported practices, difficulties and knowledge were evaluated using the Palliative Care Self-Reported Practices Scale in HF (PCPS-HF), Palliative Care Difficulties Scale in HF (PCDS-HF), and Palliative care knowledge Test in HF (PT-HF), respectively. Structural equation models (SEM) were used to estimate path coefficients for PCPS-HF, PCDS-HF, and PT-HF. A total of 207 physicians participated in the HEPT between February 2018 and July 2019, and 148 questionnaires were ultimately analyzed. The total PCPS-HF, PCDS-HF, and PT-HF scores were significantly improved 6 months after HEPT completion (61.1 vs 67.7, p<0.001, 54.9 vs 45.1, p<0.001, and 20.8 vs 25.7, p<0.001, respectively). SEM analysis showed that for pre-post difference (Dif) PCPS-HF, "clinical experience of more than 14 years" and pre-test score had significant negative effects (-2.31, p = 0.048, 0.52, p<0.001, respectively). For Dif PCDS-HF, ≥ "28 years old or older" had a significant positive direct effect (13.63, p<0.001), although the pre-test score had a negative direct effect (-0.56, p<0.001). For PT-HF, "involvement in more than 50 HF patients' treatment in the past year" showed a positive direct effect (0.72, p = 0.046), although the pre-test score showed a negative effect (-0.78, p<0.001). Physicians who completed the HEPT showed significant improvements in practice, difficulty, and knowledge scales in HF palliative care.

Sleep disturbance has the largest impact on children's behavior and emotions.

Objective: Children's behavior and emotions are affected by sleep disturbances, the parent-child relationship, media viewing time, and the social status of parents and caregivers. We conducted a questionnaire survey to identify the factors that have the greatest impact on children's behavior and emotions and how these factors relate to each other. Methods: A parental questionnaire survey was performed at a public elementary school. The questionnaire comprised questions on the family environment (e.g., family structure, media and game exposure, after-school lessons, and caregiver's work schedule) and physical information, the Strengths and Difficulties Questionnaire (SDQ), the Children's Sleep Habits Questionnaire (CSHQ), and the Pittsburgh Sleep Quality Index (PSQI) for parents' sleep condition. A path diagram was drawn to hypothesize the complex interrelationships among factors, and structural equation modeling was used to estimate the path coefficients. Result: We identified several factors that significantly affected the SDQ score. The CSHQ total score had the largest impact, followed by after-school lessons, single-mother families, and children's sex. In addition, several indirect pathways that led to the CSHQ score (i.e., a pathway from time spent watching television to CSHQ score via children's bedtime and a pathway from single-mother family to CSHQ score via PSQI total score) significantly affected the SDQ score. Conclusion: Children's sleep habits that were influenced by several environmental factors had the greatest impact on children's behavior and emotions, which suggested that children's behavioral problems can be improved by interventions focused on sleep habits, such as sleep hygiene instructions.

Comorbidities Associated With Residual Cardiovascular Risk in Patients With Chronic Coronary Syndrome Receiving Statin Therapy　- Subanalysis of the REAL-CAD Trial.

Background: Even with high-dose statin therapy, residual cardiovascular event risks remain in patients with chronic coronary syndrome (CCS). Thus, future treatment targets need to be elucidated. This study determined the factors associated with residual cardiovascular risk in patients with CCS treated with high-dose statins. Methods and Results: This study was a subanalysis of the REAL-CAD study. This study enrolled 5,540 patients with CCS receiving 4 mg/day pitavastatin and assessed the impacts of 3 representative risk factors (i.e., blood pressure, glucose level, and renal function), alone or in combination, on clinical outcomes. Each risk factor was classified according to its severity. The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, and unstable angina requiring emergency hospitalization. After adjusting for the effects of confounders, a significantly worse prognosis was observed in the group with an estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m2 (hazard ratio [HR] 1.36; 95% confidence interval 1.03-1.80; P=0.028). No other factors or combinations were associated with the primary endpoint. An eGFR ≤60 mL/min/1.73 m2 was also associated with cardiac (HR 2.38; P=0.004) and all-cause (HR 1.51; P=0.032) death. Conclusions: Insufficient renal function was associated with a worse prognosis in patients with CCS undergoing high-dose statin therapy, suggesting that renal function is the next target for reducing the risk of residual cardiovascular events.

Clinical Characteristics of Anti-TIF-1γ Antibody-Positive Dermatomyositis Associated with Malignancy.

We retrospectively analyzed the clinical and laboratory data of patients diagnosed with anti-transcriptional intermediary factor 1 (TIF-1γ) antibody-positive polymyositis (PM)/dermatomyositis (DM) to clarify the characteristics of this disease. We identified 14 patients with TIF-1γ antibody-positive DM (TIF-1γ DM), 47 with anti-aminoacyl-tRNA synthetase antibody (ARS)-positive PM/DM, and 24 with anti-melanoma differentiation-associated gene 5 antibody (MDA-5)-positive PM/DM treated at the Kurume University Hospital between 2002 and 2020. Patients with TIF-1γ DM were significantly older than the other two groups. Nine patients with TIF-1γ DM were female, thirteen patients had DM, and one had clinically amyopathic DM. Primary malignant lesions were lung (3), uterus (2), colon (2), breast (2), ovary (1), lymphoma (1), and unknown (2). Cutaneous manifestation and dysphagia were the most common symptoms in TIF-1γ DM. Erythema (9/14), the V-neck sign (8/14), heliotrope (9/14), and nailfold telangiectasia (14/14) were significantly more common in TIF-1γ DM. Furthermore, no patients with TIF-1γ DM had interstitial lung abnormality on high-resolution CT. In patients with TIF-1γ DM, the frequency of dysphagia and unusual erythema, particularly that which spreads from the trunk, and nailfold telangiectasia, were characteristic findings. In most patients with TIF-1γ DM, it is necessary to administer other immunosuppressive drugs along with glucocorticoids.