University of Tsukuba Hospital

PURPOSE: To evaluate the diagnostic performance of real-time freehand elastography by using the extended combined autocorrelation method (CAM) to differentiate benign from malignant breast lesions, with pathologic diagnosis as the reference standard. MATERIALS AND METHODS: This study was approved by the University of Tsukuba Human Subjects Institutional Review Board; all patients gave informed consent. Conventional ultrasonography (US) and real-time US elastography with CAM were performed in 111 women (mean age, 49.4 years; age range, 27-91 years) who had breast lesions (59 benign, 52 malignant). Elasticity images were assigned an elasticity score according to the degree and distribution of strain induced by light compression. The area under the curve and cutoff point, both of which were obtained by using a receiver operating characteristic curve analysis, were used to assess diagnostic performance. Mean scores were examined by using a Student t test. Sensitivity, specificity, and accuracy were compared by using the standard proportion difference test or the Delta-equivalent test. RESULTS: For elasticity score, the mean +/- standard deviation was 4.2 +/- 0.9 for malignant lesions and 2.1 +/- 1.0 for benign lesions (P < .001). When a cutoff point of between 3 and 4 was used, elastography had 86.5% sensitivity, 89.8% specificity, and 88.3% accuracy. When a best cutoff point of between 4 and 5 was used, conventional US had 71.2% sensitivity, 96.6% specificity, and 84.7% accuracy. Elastography had higher sensitivity than conventional US (P < .05). By using equivalence bands for noninferiority or equivalence, it was shown that the specificity of elastography was not inferior to that of conventional US and that the accuracy of elastography was equivalent to that of conventional US. CONCLUSION: For assessing breast lesions, US elastography with the proposed imaging classification, which was simple compared with that of the Breast Imaging Recording and Data System classification, had almost the same diagnostic performance as conventional US.

PURPOSE Patients with advanced esophageal cancer have a poor prognosis and limited treatment options after first-line chemotherapy. PATIENTS AND METHODS In this open-label, phase III study, we randomly assigned (1:1) 628 patients with advanced/metastatic squamous cell carcinoma or adenocarcinoma of the esophagus, that progressed after one prior therapy, to pembrolizumab 200 mg every 3 weeks for up to 2 years or chemotherapy (investigator’s choice of paclitaxel, docetaxel, or irinotecan). Primary end points were overall survival (OS) in patients with programmed death ligand-1 (PD-L1) combined positive score (CPS) ≥ 10, in patients with squamous cell carcinoma, and in all patients (one-sided α 0.9%, 0.8%, and 0.8%, respectively). RESULTS At final analysis, conducted 16 months after the last patient was randomly assigned, OS was prolonged with pembrolizumab versus chemotherapy for patients with CPS ≥ 10 (median, 9.3 v 6.7 months; hazard ratio [HR], 0.69 [95% CI, 0.52 to 0.93]; P = .0074). Estimated 12-month OS rate was 43% (95% CI, 33.5% to 52.1%) with pembrolizumab versus 20% (95% CI, 13.5% to 28.3%) with chemotherapy. Median OS was 8.2 months versus 7.1 months (HR, 0.78 [95% CI, 0.63 to 0.96]; P = .0095) in patients with squamous cell carcinoma and 7.1 months versus 7.1 months (HR, 0.89 [95% CI, 0.75 to 1.05]; P = .0560) in all patients. Grade 3-5 treatment-related adverse events occurred in 18.2% of patients with pembrolizumab versus 40.9% in those who underwent chemotherapy. CONCLUSION Pembrolizumab prolonged OS versus chemotherapy as second-line therapy for advanced esophageal cancer in patients with PD-L1 CPS ≥ 10, with fewer treatment-related adverse events.

RATIONALE: Acquired pulmonary alveolar proteinosis (PAP) is a syndrome characterized by pulmonary surfactant accumulation occurring in association with granulocyte/macrophage colony-stimulating factor autoantibodies (autoimmune PAP) or as a consequence of another disease (secondary PAP). Because PAP is rare, prior reports were based on limited patient numbers or a synthesis of historical data. OBJECTIVES: To describe the epidemiologic, clinical, physiologic, and laboratory features of autoimmune PAP in a large, contemporaneous cohort of patients with PAP. METHODS: Over 6 years, 248 patients with PAP were enrolled in a Japanese national registry, including 223 with autoimmune PAP. MEASUREMENTS AND MAIN RESULTS: Autoimmune PAP represented 89.9% of cases and had a minimum incidence and prevalence of 0.49 and 6.2 per million, respectively. The male to female ratio was 2.1:1, and the median age at diagnosis was 51 years. A history of smoking occurred in 56%, and dust exposure occurred in 23%; instances of familial onset did not occur. Dyspnea was the most common presenting symptom, occurring in 54.3%. Importantly, 31.8% of patients were asymptomatic and were identified by health screening. Intercurrent illnesses, including infections, were infrequent. A disease severity score reflecting the presence of symptoms and degree of hypoxemia correlated well with carbon monoxide diffusing capacity and serum biomarkers, less well with pulmonary function, and not with granulocyte/macrophage colony-stimulating factor autoantibody levels or duration of disease. CONCLUSIONS: Autoimmune PAP had an incidence and prevalence higher than previously reported and was not strongly linked to smoking, occupational exposure, or other illnesses. The disease severity score and biomarkers provide novel and potentially useful outcome measures in PAP.

Loss of heterozygosity (LOH) at locus 10q23.3 and mutation of the PTEN tumor suppressor gene occur frequently in both endometrial carcinoma and ovarian endometrioid carcinoma. To investigate the potential role of the PTEN gene in the carcinogenesis of ovarian endometrioid carcinoma and its related subtype, clear cell carcinoma, we examined 20 ovarian endometrioid carcinomas, 24 clear cell carcinomas, and 34 solitary endometrial cysts of the ovary for LOH at 10q23.3 and point mutations within the entire coding region of the PTEN gene. LOH was found in 8 of 19 ovarian endometrioid carcinomas (42.1%), 6 of 22 clear cell carcinomas (27.3%), and 13 of 23 solitary endometrial cysts (56.5%). In 5 endometrioid carcinomas synchronous with endometriosis, 3 cases displayed LOH events common to both the carcinoma and the endometriosis, 1 displayed an LOH event in only the carcinoma, and 1 displayed no LOH events in either lesion. In 7 clear cell carcinomas synchronous with endometriosis, 3 displayed LOH events common to both the carcinoma and the endometriosis, 1 displayed an LOH event in only the carcinoma, and 3 displayed no LOH events in either lesion. In no cases were there LOH events in the endometriosis only. Somatic mutations in the PTEN gene were identified in 4 of 20 ovarian endometrioid carcinomas (20.0%), 2 of 24 clear cell carcinomas (8.3%), and 7 of 34 solitary endometrial cysts (20.6%). These results indicate that inactivation of the PTEN tumor suppressor gene is an early event in the development of ovarian endometrioid carcinoma and clear cell carcinoma of the ovary.

PURPOSE: This prospective study was conducted to assess the influence of overnight orthokeratology (OK) on axial elongation in children, with those wearing spectacles as controls. METHODS: One hundred five subjects (210 eyes) were enrolled in the study. The OK group comprised 45 patients (90 eyes, age 12.1 ± 2.5 years, mean ± SD; OK group) who matched the inclusion criteria for OK. The control group comprised 60 patients (120 eyes, 11.9 ± 2.0 years) who also matched the inclusion criteria for OK but preferred spectacles for myopia correction. Axial length was measured at baseline and after 2 years using ocular biometry, and the changes were evaluated and compared between the groups. RESULTS: Ninety-two subjects (42 and 50 in the OK and control groups, respectively) completed the 2-year follow-up examinations. At baseline, the spherical equivalent refractive error was -2.55 ± 1.82 and -2.59 ± 1.66 D, and the axial length was 24.66 ± 1.11 and 24.79 ± 0.80 mm in the OK and control groups, respectively, with no significant differences between the groups. The increase in axial length during the 2-year study period was 0.39 ± 0.27 and 0.61 ± 0.24 mm, respectively, and the difference was significant (P < 0.0001, unpaired t-test). CONCLUSIONS: OK suppressed axial elongation in myopic children, suggesting that this treatment can slow the progression of myopia to a certain extent.

This paper presents a blind source separation method for convolutive mixtures of speech/audio sources. The method can even be applied to an underdetermined case where there are fewer microphones than sources. The separation operation is performed in the frequency domain and consists of two stages. In the first stage, frequency-domain mixture samples are clustered into each source by an expectation-maximization (EM) algorithm. Since the clustering is performed in a frequency bin-wise manner, the permutation ambiguities of the bin-wise clustered samples should be aligned. This is solved in the second stage by using the probability on how likely each sample belongs to the assigned class. This two-stage structure makes it possible to attain a good separation even under reverberant conditions. Experimental results for separating four speech signals with three microphones under reverberant conditions show the superiority of the new method over existing methods. We also report separation results for a benchmark data set and live recordings of speech mixtures.

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created as revised from J-SSCG 2016 jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in September 2020 and published in February 2021. An English-language version of these guidelines was created based on the contents of the original Japanese-language version. The purpose of this guideline is to assist medical staff in making appropriate decisions to improve the prognosis of patients undergoing treatment for sepsis and septic shock. We aimed to provide high-quality guidelines that are easy to use and understand for specialists, general clinicians, and multidisciplinary medical professionals. J-SSCG 2016 took up new subjects that were not present in SSCG 2016 (e.g., ICU-acquired weakness [ICU-AW], post-intensive care syndrome [PICS], and body temperature management). The J-SSCG 2020 covered a total of 22 areas with four additional new areas (patient- and family-centered care, sepsis treatment system, neuro-intensive treatment, and stress ulcers). A total of 118 important clinical issues (clinical questions, CQs) were extracted regardless of the presence or absence of evidence. These CQs also include those that have been given particular focus within Japan. This is a large-scale guideline covering multiple fields; thus, in addition to the 25 committee members, we had the participation and support of a total of 226 members who are professionals (physicians, nurses, physiotherapists, clinical engineers, and pharmacists) and medical workers with a history of sepsis or critical illness. The GRADE method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members.As a result, 79 GRADE-based recommendations, 5 Good Practice Statements (GPS), 18 expert consensuses, 27 answers to background questions (BQs), and summaries of definitions and diagnosis of sepsis were created as responses to 118 CQs. We also incorporated visual information for each CQ according to the time course of treatment, and we will also distribute this as an app. The J-SSCG 2020 is expected to be widely used as a useful bedside guideline in the field of sepsis treatment both in Japan and overseas involving multiple disciplines.

The role of CD4(+) vs CD8(+) T cells in contact hypersensitivity (CHS) remains controversial. In this study, we used gene knockout (KO) mice deficient in CD4(+) or CD8(+) T cells to directly address this issue. Mice lacking either CD4(+) or CD8(+) T cells demonstrated depressed CHS responses to dinitrofluorobenzene and oxazolone compared with wild-type C57BL/6 mice. The depression of CHS was more significant in CD8 KO mice than in CD4 KO mice. Furthermore, in vivo depletion of either CD8(+) T cells from CD4 KO mice or CD4(+) T cells from CD8 KO mice virtually abolished CHS responses. Lymph node cells (LNCs) from hapten-sensitized CD4 and CD8 KO mice showed a decreased capacity for transferring CHS. In vitro depletion of either CD4(+) T cells from CD8 KO LNCs or CD8(+) T cells from CD4 KO LNCs resulted in a complete loss of CHS transfer. LNCs from CD4 and CD8 KO mice produced significant amounts of IFN-gamma, indicating that both CD4(+) and CD8(+) T cells are able to secrete IFN-gamma. LNCs from CD8, but not CD4, KO mice were able to produce IL-4 and IL-10, suggesting that IL-4 and IL-10 are mainly derived from CD4(+) T cells. Intracellular cytokine staining of LNCs confirmed that IFN-gamma-positive cells consisted of CD4(+) (Th1) and CD8(+) (type 1 cytotoxic T) T cells, whereas IL-10-positive cells were exclusively CD4(+) (Th2) T cells. Collectively, these results suggest that both CD4(+) Th1 and CD8(+) type 1 cytotoxic T cells are crucial effector cells in CHS responses to dinitrofluorobenzene and oxazolone in C57BL/6 mice.

Magnetic resonance (MR) imaging is useful not only for preoperative staging of gynecologic malignancies but also for prediction of the histopathologic features of a variety of intrapelvic tumors. Familiarity with the specific imaging findings that have been reported for the uterine cervix is a goal of radiologists. The typical MR imaging findings of uterine cervical lesions correspond to the histopathologic features. These lesions can be categorized as epithelial neoplasms, nonepithelial neoplasms, and nonneoplastic diseases. Cervical carcinoma accounts for most cases of malignant lesions and is staged by using the classification system established by the International Federation of Gynecology and Obstetrics. MR imaging allows differentiation between endophytic and exophytic growth and between normal and abnormal findings after hysterectomy and irradiation. Other epithelial neoplasms of the uterine cervix include adenoma malignum, which is a special type of cervical adenocarcinoma, as well as carcinoid tumor and malignant melanoma. Nonepithelial neoplasms of the uterine cervix include malignant lymphoma and leiomyoma. Nonneoplastic diseases of the uterine cervix include cervical pregnancy, cervicitis, nabothian cysts, polyps, and endometriosis.

Germ cell tumors (GCTs) occur most frequently in the gonads and are relatively rare in other sites, such as the pineal gland, neurohypophysis, mediastinum, and retroperitoneum. GCTs are thought to originate from primordial germ cells, which migrate to the primitive gonadal glands in the urogenital ridge. Extragonadal GCTs might also originate from these cells when the cells are sequestered during their migration. Pathologic subtypes of GCTs vary, and the prevalence of mixed tumors is high. These factors produce a diversity of radiologic findings and make prospective radiologic diagnosis difficult in many cases. However, similar radiologic findings have been observed in pathologically equivalent tumors in varying sites. Seminomas appear as uniformly solid, lobulated masses with fibrovascular septa that enhance intensely. Nonseminomatous GCTs appear as heterogeneous masses with areas of necrosis, hemorrhage, or cystic degeneration. Fat and calcifications are hallmarks of teratomas, most of which are benign. In immature teratomas, scattered fat and calcification within larger solid components are occasionally seen. These imaging characteristics reflect the pathologic features of each tumor, and histologically similar GCTs at varying sites have similar radiologic features. Knowledge of the pathologic appearances of GCTs and their corresponding radiologic appearances will allow radiologists to diagnose these tumors correctly.

PURPOSE This phase III, multicenter, randomized, open-label study investigated the efficacy and safety of nivolumab versus chemotherapy (gemcitabine [GEM] or pegylated liposomal doxorubicin [PLD]) in patients with platinum-resistant ovarian cancer. MATERIALS AND METHODS Eligible patients had platinum-resistant epithelial ovarian cancer, received ≤ 1 regimen after diagnosis of resistance, and had an Eastern Cooperative Oncology Group performance score of ≤ 1. Patients were randomly assigned 1:1 to nivolumab (240 mg once every 2 weeks [as one cycle]) or chemotherapy (GEM 1000 mg/m 2 for 30 minutes [once on days 1, 8, and 15] followed by a week's rest [as one cycle], or PLD 50 mg/m 2 once every 4 weeks [as one cycle]). The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), overall response rate, duration of response, and safety. RESULTS Patients (n = 316) were randomly assigned to nivolumab (n = 157) or GEM or PLD (n = 159) between October 2015 and December 2017. Median OS was 10.1 (95% CI, 8.3 to 14.1) and 12.1 (95% CI, 9.3 to 15.3) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.0; 95% CI, 0.8 to 1.3; P = .808). Median PFS was 2.0 (95% CI, 1.9 to 2.2) and 3.8 (95% CI, 3.6 to 4.2) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.5; 95% CI, 1.2 to 1.9; P = .002). There was no statistical difference in overall response rate between groups (7.6% v 13.2%; odds ratio, 0.6; 95% CI, 0.2 to 1.3; P = .191). Median duration of response was numerically longer with nivolumab than GEM or PLD (18.7 v 7.4 months). Fewer treatment-related adverse events were observed with nivolumab versus GEM or PLD (61.5% v 98.1%), with no additional or new safety risks. CONCLUSION Although well-tolerated, nivolumab did not improve OS and showed worse PFS compared with GEM or PLD in patients with platinum-resistant ovarian cancer.

BACKGROUND: In patients with atrial fibrillation (AF), most thrombus forms in the left atrial appendage (LAA). However, the relation of LAA morphology with LAA thrombus is unknown. METHODS AND RESULTS: We prospectively enrolled 633 consecutive patients who were candidates for catheter ablation for symptomatic drug-resistant AF. Transesophageal echocardiography (TEE) was performed to assess LAA thrombus. LAA structure was assessed by 3-dimensional TEE. LAA orifice area, depth, volume, and number of lobes were measured on reconstructed 3-dimensional images. Clinical characteristics and echocardiographic measures were compared to determine variables predicting LAA thrombus. Excluded were 69 (10.9%) patients who met the exclusion criteria. Finally, this study comprised 564 patients, of whom LAA thrombus was observed in 36 (6.4%) patients. Multivariate analysis revealed CHADS2 (Congestive heart failure, Hypertension Age>75, Diabetes mellitus and prior Stroke or transient ischemic attack) score (P=0.002), left ventricular ejection fraction (P=0.01), degree of spontaneous echo contrast (P=0.02), left atrial volume (P=0.02), and number of LAA lobes (P<0.001) to be independently associated with thrombus formation. Most patients with LAA thrombus (32/34, 94.4%) had ≥3 LAA lobes, whereas LAA thrombus was observed in only 2 (0.7%) of 296 patients with 1 or 2 lobes. LAA volume significantly decreased in patients maintaining sinus rhythm after catheter ablation (P=0.0009). Number of LAA lobes did not change in any patient. CONCLUSIONS: Complex LAA morphology characterized by an increased number of LAA lobes was associated with the presence of LAA thrombus independently of clinical risk and blood stasis. This study suggests that LAA morphology might be a congenital risk factor for LAA thrombus formation in patients with AF.

Kabuki syndrome is a congenital anomaly syndrome characterized by developmental delay, intellectual disability, specific facial features including long palpebral fissures and ectropion of the lateral third of the lower eyelids, prominent digit pads, and skeletal and visceral abnormalities. Mutations in MLL2 and KDM6A cause Kabuki syndrome. We screened 81 individuals with Kabuki syndrome for mutations in these genes by conventional methods (n = 58) and/or targeted resequencing (n = 45) or whole exome sequencing (n = 5). We identified a mutation in MLL2 or KDM6A in 50 (61.7%) and 5 (6.2%) cases, respectively. Thirty-five MLL2 mutations and two KDM6A mutations were novel. Non-protein truncating-type MLL2 mutations were mainly located around functional domains, while truncating-type mutations were scattered through the entire coding region. The facial features of patients in the MLL2 truncating-type mutation group were typical based on those of the 10 originally reported patients with Kabuki syndrome; those of the other groups were less typical. High arched eyebrows, short fifth finger, and hypotonia in infancy were more frequent in the MLL2 mutation group than in the KDM6A mutation group. Short stature and postnatal growth retardation were observed in all individuals with KDM6A mutations, but in only half of the group with MLL2 mutations.

Since the first report in 1976, accumulated clinical evidence has supported intravesical Bacillus Calmette-Guerin (BCG) therapy as one of the standard methods of management of intermediate- and high-risk non-muscle invasive bladder cancer. Despite its efficacy, intravesical BCG therapy is associated with a variety of adverse events (AEs), most of which are tolerable or controllable with supportive care. However, some patients receiving intravesical BCG therapy may experience uncommon but severe AEs, leading to cessation of BCG therapy. Not all, but most severe AEs result from either local or systemic infection with live BCG. Intravesical instillation of BCG elicits multiple immune reactions, although the precise immunological mechanism of BCG therapy is not clear. It is convenient to separate the complex reactions into the following three categories: infection of urothelial cells or bladder cancer cells, induction of immune reactions, and induction of antitumor effects. Recently, our knowledge about each category has increased. Based on this understanding, predictors of the efficacy of intravesical BCG therapy, such as urinary cytokine measurement and cytokine gene polymorphism, have been investigated. Recently, preclinical studies using a novel engineered mycobacterium vaccine have been conducted to overcome the limitations of BCG therapy. One approach is Th1 cytokine-expressing recombinant forms of BCG; another approach is development of non-live bacterial agents to avoid AEs due to live BCG infection. We also briefly describe our approach using an octaarginine-modified liposome-incorporating BCG cell wall component to develop future substitutes for live BCG.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Co‐administration of proton pump inhibitors (PPIs) increases plasma methotrexate (MTX) concentration in cancer patients receiving high‐dose MTX (HDMTX) therapy. • There is controversy as to whether or not co‐administration of PPIs affects plasma MTX elimination in HDMTX therapy. • Inhibitory activity of PPIs on breast cancer resistance protein (BCRP) is a possible mechanism for the drug interaction between MTX and PPIs. WHAT THIS STUDY ADDS • Co‐administration of a PPI (omeprazole, lansoprazole, or rabeprazole) was more frequently observed in the delayed MTX elimination group than in the normal MTX elimination group. • Multiple logistic regression analysis with adjustment for significant covariates revealed that PPI co‐administration was a significant risk factor for delayed plasma MTX elimination. • The half‐maximal inhibitory concentration of each PPI in inhibiting BCRP function was much higher than the therapeutic unbound concentration in the plasma. AIM To assess whether or not co‐administration of proton pump inhibitors (PPIs) is a risk factor for delayed elimination of plasma methotrexate (MTX) in high‐dose MTX (HDMTX) therapy for malignant diseases. METHODS To assess the effects of PPI co‐administration on elimination of plasma MTX, we examined plasma MTX concentration data on 171 cycles of HDMTX therapy performed in 74 patients. We performed multiple logistic regression analysis to evaluate PPI co‐administration as a risk factor. Inhibitory potencies of omeprazole, lansoprazole, rabeprazole and pantoprazole on MTX transport via breast cancer resistance protein (BCRP, ABCG2) were also investigated in an in vitro study using membrane vesicles expressing human BCRP. RESULTS We identified co‐administration of PPIs as a risk factor for delayed elimination (odds ratio 2.65, 95% confidence interval 1.03, 6.82) as well as renal and liver dysfunction. All four PPIs inhibited BCRP‐mediated transport of MTX, with half‐maximal inhibitory concentrations of 5.5–17.6 µM – considerably higher than the unbound plasma concentrations of the PPIs. CONCLUSIONS Our results support previous findings suggesting that PPI co‐administration is associated with delayed elimination of plasma MTX in patients with HDMTX therapy. This drug interaction, however, cannot be explained solely by the inhibitory effects of PPIs on BCRP‐mediated MTX transport.

Japan's health system is well known for achieving one of the world's highest life expectancy with universal health coverage. However, the country now faces challenges of a rapidly aging population and changes in patterns and burden of disease. Primary care is an important component of a well-functioning health system. In Japan, primary care services are provided in both the community and hospital settings. The distinction between primary and secondary care may not always be clear. This review is based on the framework from the 2015 WHO publication on primary care systems in Europe. Our aim is to describe the journey of primary care in Japan, with its past, present, and future as a valuable addition to the academic English literature. We also hope that this article would inspire readers outside of Japan who might face similar issues in their respective countries.

OBJECTIVE: We investigated how regional body composition measured by dual-energy X-ray absorptiometry (DXA) is associated with risk factors for coronary heart disease (CHD) during weight reduction in obese women. METHODS AND RESULTS: Data were gathered from 128 overweight and obese women, aged 34 to 66 years, during a 14-week intervention study with diet and exercise. Regional (arms, legs, and trunk) fat tissue (FT) and lean soft tissue (LST) were measured by DXA. The FT change in legs correlated negatively with changes in diastolic blood pressure, low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), and the number of CHD risk factors per subject (r=-0.17, P<0.05 to -0.26, P<0.01) in response to weight reduction, whereas truncal FT change had positive correlations with changes in triglycerides, LDL-C, FPG, and the number of CHD risk factors per subject (r=0.17, P<0.05 to 0.25, P<0.01). LST change in legs correlated negatively with changes in systolic blood pressure, FPG, and the number of risk factors (r=-0.20 to -0.21, P<0.05). CONCLUSIONS: Regional body composition information is important for evaluating improvement of CHD risk factors during weight-reduction treatment for obesity; differential FTs had opposing effects on CHD risk factors during weight reduction in obese women.

Abstract Coronavirus disease 2019 (COVID‐19) often causes radiological and functional pulmonary sequelae. However, evidence on 1‐year follow‐up of pulmonary sequelae is limited. We aimed to investigate the characteristics and time‐course of pulmonary sequelae after recovery from COVID‐19 through 1‐year follow‐up. We searched PubMed and EMBASE databases on 25 February 2022, and included studies with computed tomography (CT) findings at the 1‐year follow‐up. The extracted data on CT findings were analysed using a one‐group meta‐analysis. We further analysed the data in relation to COVID‐19 severity, improvement rate and lung function. Fifteen eligible studies ( N = 3134) were included. One year after COVID‐19, 32.6% (95% CI 24.0–42.6, I 2 = 92.9%) presented with residual CT abnormalities. Ground‐glass opacity and fibrotic‐like changes were frequently observed in 21.2% (95% CI 15.4–28.4, I 2 = 86.7%) and 20.6% (95% CI 11.0–35.2, I 2 = 91.9%), respectively. While the gradual recovery was seen on CT (52.9% [mid‐term] vs. 32.6% [1 year]), the frequency of CT abnormalities was higher in the severe/critical cases than in the mild/moderate cases (37.7% vs. 20.7%). In particular, fibrotic changes showed little improvement between 4–7 months and 1 year after COVID‐19. Pulmonary function tests at 1 year also showed the decline in diffusing capacity of the lung for carbon monoxide, especially in severe/critical cases. Our meta‐analysis indicated that residual CT abnormalities were common in hospitalized COVID‐19 patients 1 year after recovery, especially fibrotic changes in severe/critical cases. As these sequelae may last long, vigilant observations and longer follow‐up periods are warranted.

We compared the effects of 12-week programs of resistance training (RT), high-intensity interval aerobic training (HIAT), and moderate-intensity continuous aerobic training (MICT). The primary goal was to evaluate the therapeutic effects of the exercise modalities for the management of nonalcoholic fatty liver disease (NAFLD). A total of 61 sedentary obese men with NAFLD were randomized into one of the following exercise regimens (RT, HIAT, or MICT). Hepatic fat content was decreased to a similar extent in the RT, HIAT, and MICT groups (-14.3% vs. -13.7% vs. -14.3%) without significant changes in weight and visceral fat. The gene expression levels of fatty acid synthesis were significantly decreased in the subjects' monocytes. Hepatic stiffness was decreased only in the HIAT group (-16.8%). The stiffness change was associated with restored Kupffer cell phagocytic function (+17.8%) and decreased levels of inflammation such as leptin (-13.2%) and ferritin (-14.1%). RT, HIAT, and MICT were equally effective in reducing hepatic fat content, but only HIAT was effective in improving hepatic stiffness and restoring Kupffer cell function. These benefits appeared to be independent of detectable weight and visceral fat reductions; the benefits were acquired through the modulation of in vivo fatty acid metabolism and obesity-related inflammatory conditions.

BACKGROUND: In Japan, some residents develop mental health problems. In previous studies, it was reported that long working hours might be a cause of stress reaction such as depression. There were some reports that compared residents with 80 or more working hours with those with less than 80 working hours. However, many residents are practically detained for extra-long time, designated as 100 h or more per week, for medical practice, training, self-study, etc. There have been few reports on extra-long hours of work. This study evaluated the working environment and the amount of stress experienced by first-year residents, and examined the relationship between long working hours and depression, especially in the group of extra-long working hours. METHODS: The study included 1241 first-year residents employed at 250 training hospitals in 2011. A self-report questionnaire was administered at the beginning of the residency and 3 months later to collect data on demographics, depressive symptoms, and training conditions (e.g., duration of work, sleep, disposable time, and night shift). Depressive symptoms were rated using the Center for Epidemiologic Studies Depression Scale. RESULTS: The mean duration of work per week was 79.4 h, with 97 residents (7.8%) working 100 h or more. At 3 months, clinically significant depressive symptoms were reported by 45.5% of residents working 100 or more h per week, which proportion was significantly greater than that for respondents working less than 60 h (P < 0.001). Multivariate logistic regression analysis showed that a working week of 80 to 99.9 h was associated with a 2.83 fold higher risk and 100 h or more was associated with a 6.96-fold higher risk of developing depressive symptoms compared with a working week of less than 60 h. CONCLUSION: Working excessively long hours was significantly associated with development of depressive symptoms. Proper management of resident physicians' working hours is critical to maintaining their physical and mental health and to improve the quality of care they provide.