Smartphone-Based Digital Peer Support for a Walking Intervention Among Public Officers in Kanagawa Prefecture: Single-Arm Pre- and Postintervention Evaluation.

BACKGROUND: Digital peer support, defined as peer support delivered through technology such as smartphone apps, may be promising to promote activity in the form of step counts. Interactions among users have a positive impact on retention rates, and apps with social elements show significant improvements in daily step count. However, the feasibility of digital peer support in promoting physical activity (PA) is unknown; therefore, its effectiveness on step count and the clinical implications remain unconfirmed. OBJECTIVE: This study aimed to assess the feasibility of digital peer support over a 3-month intervention period using the retention rate as the outcome. Moreover, changes in daily step count and physical measurements were compared between pre- and postintervention. METHODS: The study design was a 3-month 1-arm intervention with participants from local government offices in Kanagawa, Japan. We used an available smartphone app, Minchalle, as the tool for the group intervention. Participants were required to report their daily step count to a maximum of 5 members composed exclusively of study participants. The primary outcome was the retention rate. Secondary outcomes included daily step count, the rate of achieving daily step goals, physical measurements, and lifestyle characteristics. Descriptive statistics and the Pearson coefficient were used to examine the relationship between goal achievement and step count, as well as changes in step count and various variables including physical measurements. RESULTS: Of the 63 participants, 62 completed the intervention. The retention rate was 98% (62/63). The average daily step count during the intervention was 6993 (SD 2328) steps, an 1182-step increase compared with the count observed 1 week before the intervention began. The rate of achieving the daily step count during the intervention was 53.5% (SD 26.2%). There was a significant correlation (r=0.27, P=.05) between achieving daily step goals and increasing daily step count. Comparative analyses showed that changes in weight (68.56, SD 16.97 kg vs 67.30, SD 16.86 kg; P<.001), BMI (24.82, SD 4.80 kg/m2 vs 24.35, SD 4.73 kg/m2; P<.001), somatic fat rate (28.50%, SD 7.44% vs 26.58%, SD 7.90%; P=.005), systolic blood pressure (130.42, SD 17.92 mm Hg vs 122.00, SD 15.06 mm Hg; P<.001), and diastolic blood pressure (83.24, SD 13.27 mm Hg vs 77.92, SD 11.71 mm Hg; P=.002) were significantly different before and after the intervention. Similarly, the daily amount of PA significantly improved from 5.77 (SD 3.81) metabolic equivalent (MET)-hours per day to 9.85 (SD 7.84) MET-hours per day (P<.001). CONCLUSIONS: This study demonstrated that digital peer support is feasible for maintaining a high retention rate and can, therefore, effectively promote PA. It can be a promising tool to improve daily step count, subjective PA, and clinical outcomes, such as weight and somatic fat rate. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000042520; https://tinyurl.com/46c4nm8z.

High serum growth differentiation factor 15 is a risk factor for the occurrence of hepatocellular carcinoma in chronic hepatitis B patients treated with nucleos(t)ide analogs.

AIM: Patients with chronic hepatitis B (CHB) remain at risk for hepatocellular carcinoma (HCC) even with nucleos(t)ide analog therapy. We evaluated risk factors for HCC development, including serum hepatitis B virus (HBV) RNA, hepatitis B core-related antigen level, and growth differentiation factor 15 (GDF15) level, a predictor of HCC development in patients with chronic hepatitis C. METHODS: We collected clinical data and stored serum from CHB patients without a history of HCC who were receiving nucleos(t)ide analog treatment for more than 1 year and whose HBV DNA level was less than 3.0 log IU/mL. We measured the serum levels of HBV RNA and GDF15. RESULTS: Among 242 CHB patients, 57 had detectable HBV RNA, and GDF15 was quantified in all patients. The median GDF15 level was 0.86 ng/mL. Cox proportional hazards analysis revealed that male sex and higher GDF15, FIB-4 index, alpha-fetoprotein and gamma-glutamyl transpeptidase were independent risk factors for HCC. The presence of HBV RNA above the lower limit of quantification was not a risk factor. When we set cutoff values based on the Youden index, the cumulative incidence of HCC was significantly higher in the male, AFP ≥3.0 ng/mL, gamma-glutamyl transpeptidase ≥22 U/L, FIB-4 index ≥1.93, and GDF-15 ≥1.17 ng/mL groups. In patients with no or more than three of these five risk factors, the 10-year HCC cumulative incidence rates were 0% and 41.0%, respectively. CONCLUSIONS: High serum GDF15 is an independent risk factor for the occurrence of HCC in CHB patients treated with nucleos(t)ide analogs.

Efficacy of exercise with the hybrid assistive limb lumbar type on physical function in mobility-limited older adults: A 5-week randomized controlled trial.

BACKGROUND: Sarcopenia and frailty often worsen in older adults because of declines in activities of daily living and social connections that are associated with chronic diseases and traumatic injuries such as falls and fractures. Exercise intervention for sarcopenia can take >3 months to improve muscle mass, muscle strength, and walking speed. Thus, a specialized intervention system for shorter periods of time is needed. In this study, we aimed to evaluate the short-term efficacy of an exercise program using the wearable cyborg Hybrid Assistive Limb (HAL) lumbar type in physical function in mobility-limited older adults who do not require transition to long-term care. METHODS: This randomized, single-blind, parallel-group study involved 79 community-dwelling older adults with physical frailty or locomotive syndrome assigned to an intervention group (n = 40) with the HAL lumbar type exercise program or a control group (n = 39) without the exercise program. The intervention group underwent trunk training (including trunk and hip flexion, standing and sitting from a single sitting position, and squats) and gait training (treadmill and parallel bars) twice a week for 5 weeks while wearing the HAL lumbar type. The 10-m usual and maximum walking speeds, Timed Up and Go test results, 5-times chair-standing test results, 5-question Geriatric Locomotive Function Scale (GLFS-5) scores, body-fat percentage, and muscle mass were measured before and after the intervention and analyzed using the intention-to-treat method. RESULTS: The intervention (23 % male; mean age, 74.7 ± 4.7 years) and control (21 % male; mean age, 75.1 ± 4.1 years) groups did not differ significantly in baseline characteristics. Seventy-seven participants completed the program; two withdrew for personal reasons. The mean difference (standard error) between the groups for the primary outcome (usual walking speed) was 0.35 (0.04) m/s; the time-by-group interaction was significant (p < 0.001). Secondary outcomes (maximum walking speed, Timed Up and Go test results, 5-times chair-standing test results, and GLFS-5 scores) significantly improved in the intervention group. Body composition was unchanged in both groups. CONCLUSIONS: A 5-week exercise program using the HAL lumbar type is a promising option for community-dwelling older adults with limited mobility who do not require nursing care, resulting in clinically meaningful improvements in most physical functions within a short period.

Streptococcal Toxic Shock Syndrome with Multiple Cerebral Infarctions Caused by Streptococcus dysgalactiae subsp. equisimilis: An Autopsy Case Report.

We herein report an autopsy case of streptococcal toxic shock syndrome with disseminated intravascular coagulation and multiple cerebral infarctions induced by Streptococcus dysgalactiae subsp. equisimilis (STSS) in an 84-year-old male. Pathological examination revealed sepsis with hemophagocytosis in the reticular system and intravascular bacteria in multiple organs, originating from bacterial necrotizing fasciitis of the lower extremities. The brain MRI findings showed a DWI-FLAIR mismatch, whereas the pathology was almost normal, thus supporting a hyperacute phase of cerebral infarction. The findings in this case help to elucidate the pathogenesis of STSS and develop appropriate treatment strategies.

[Association between indoor temperature during winter and falls at home in the past year among community-dwelling older adults: A cross-sectional analysis of the nationwide Smart Wellness Housing survey in Japan].

AIM: Some studies have reported a higher incidence of falls during winter with similar proportions of indoor and outdoor falls. We investigated the relationship between indoor temperature during winter and falls at home in the past year among community-dwelling older adults. METHODS: This cross-sectional study enrolled 964 individuals of ≥65 years of age in Japan. Participants answered questions about falls (including trips) at home within the past year, and the living room temperature was measured for 2 weeks during winter. Participants were divided into those living in cold (mean temperature near the floor <12°C), slightly cold (12-17.9°C), and warm (≥18°C) houses. The association between indoor temperature (cold vs. slightly cold vs. warm houses) and falls at home in the past year was examined using a logistic regression analysis adjusted for potential confounding factors. RESULTS: Valid data were obtained from 907 participants (mean age: 72.0±6.3 years), of whom 265,553, and 89 lived in cold, slightly cold, and warm houses, respectively. In the past year, falls occurred once in 325 (35.8%) participants and multiple times in 148 (16.3%) participants. In warm houses, the odds ratio of falling once and multiple times in the past year was 0.49 (p=0.032) and 0.34 (p=0.035), respectively, in comparison to cold houses. CONCLUSIONS: Living in cold houses may be associated with an increased risk of falling at home among older adults. Maintaining an appropriate indoor thermal environment during winter may reduce the risk of falling among individuals who spend most of their time at home.

Epidemiology of adverse events related to sports among community people: a scoping review.

OBJECTIVES: Numerous reports have described injuries and illnesses in competitive athletes, but studies on leisure-time physical activity and associated adverse events in the general population have not been adequately reviewed. This study aimed to summarise the previous findings on this topic. DESIGN: Scoping review. DATA SOURCES: PubMed and Ichushi-Web for articles in English and Japanese, respectively (13 April 2023). ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Articles on adverse events related to sports performed by 'individuals and groups active in the community' were included, whereas those on elite athletes, exercise therapy and rehabilitation, and school sports were excluded. Terms related to physical activity, exercise, sports and adverse events were used for the search strategies. RESULTS: The literature search yielded 67 eligible articles. Most articles were from the USA, Japan and Australia. Running, scuba diving, rugby and soccer were the most commonly reported sports. Adults were the most common age category in the samples. The most commonly reported adverse events were injuries; only 10 articles reported diseases. 13 longitudinal studies reported the frequency of adverse events based on the number of events/participants×exposure. CONCLUSION: Adverse events such as sports trauma, disability and certain diseases occur sometimes during sporting activities by residents; however, the articles identified in this review showed biases related to the countries and regions where they were published and the sports disciplines and types of adverse events reported, and articles reporting the frequency of adverse events were also limited. This highlights the need for more high-quality observational studies on diverse populations in the future.

Serum growth differentiation factor 15 is a novel biomarker with high predictive capability for liver cancer occurrence in patients with MASLD regardless of liver fibrosis.

BACKGROUND AND AIMS: Although metabolic dysfunction-associated steatotic liver disease (MASLD) patients with a Fib-4 index >1.3 are recommended for fibrosis evaluation via elastography or biopsy, a more convenient method identifying high-risk populations requiring follow-up is needed. We explored the utility of serum levels of growth differentiation factor-15 (GDF15), a cell stress-responsive cytokine related to metabolic syndrome, for stratifying the risk of clinical events in MASLD patients. METHODS: Serum GDF15 levels were measured in 518 biopsy-performed MASLD patients, 216 MASLD patients for validation, and 361 health checkup recipients with MASLD. RESULTS: In the biopsy-MASLD cohort, multivariate analysis indicated that the serum GDF15 level was a risk factor for liver cancer, independent of the fibrosis stage or Fib-4 index. Using a GDF15 cutoff of 1.75 ng/mL based on the Youden index, high-GDF15 patients, regardless of fibrosis status, had a higher liver cancer incidence rate. While patients with a Fib-4 index <1.3 or low-GDF15 rarely developed liver cancer, high-GDF15 patients with a Fib-4 index >1.3 developed liver cancer and decompensated liver events at significantly higher rates and had poorer prognoses. In the validation cohort, high-GDF15 patients had significantly higher incidences of liver cancer and decompensated liver events and poorer prognoses than low-GDF15 patients, whether limited to high-Fib-4 patients. Among health checkup recipients with MASLD, 23.0% had a Fib-4 index >1.3, 2.7% had a Fib-4 index >1.3 and >1.75 ng/mL GDF15. CONCLUSIONS: Serum GDF15 is a biomarker for liver cancer with high predictive capability and is useful for identifying MASLD patients requiring regular surveillance.

The serum tenascin C level is a marker of metabolic disorder-related inflammation affecting pancreatic cancer prognosis.

Obesity is a risk factor for pancreatic cancer development, partly due to the tissue environment of metabolic disorder-related inflammation. We aimed to detect a tissue environment marker triggered by obesity-related metabolic disorders related to pancreatic cancer progression. In murine experiments, Bl6/j mice fed a normal diet (ND) or a high-fat diet (HFD) were orthotopically injected with mPKC1, a murine-derived pancreatic cancer cell line. We used stocked sera from 140 pancreatic cancer patients for analysis and 14 colon polyp patients as a disease control. Compared with ND-fed mice, HFD-fed mice exhibited obesity, larger tumors, and worse prognoses. RNA sequencing of tumors identified tenascin C (TNC) as a candidate obesity-related serum tissue environment marker with elevated expression in tumors of HFD-fed mice. Serum TNC levels were greater in HFD-fed mice than in ND-fed mice. In pancreatic cancer patients, serum TNC levels were greater than those in controls. The TNC-high group had more metabolic disorders and greater CA19-9 levels than did the TNC-low group. There was no relationship between serum TNC levels and disease stage. Among 77 metastatic patients treated with chemotherapy, a high serum TNC concentration was an independent poor prognostic factor. Pancreatic cancer patients with high serum TNC levels experienced progression more rapidly.

Interstitial lung disease with prolonged fever that occurred during long-term administration of olaparib in a 74-year-old ovarian cancer patient: Radiological features and considerations for preventing delayed diagnosis.

A 74-year-old woman, who had been receiving olaparib for the treatment of ovarian cancer for more than a year, visited the emergency department complaining of a fever that had lasted for 1 month. She had been taking antipyretics and antibiotics for her fever, but without any effect. Although she had no symptoms other than fever, she had stopped taking olaparib for 1 week before her visit because she had developed anemia caused by myelosuppression from olaparib. After discontinuing olaparib, her maximum body temperature decreased. On admission, chest X-ray revealed no abnormalities, but chest CT showed diffuse ground-glass opacities. Chest CT taken 5 days later showed partial improvement; therefore, we diagnosed her with interstitial lung disease (ILD) associated with olaparib. After short-term steroid treatment, the ground-glass opacities disappeared, and the patient became afebrile. The CT scan taken for tumor evaluation 2 days before the onset of fever showed a few centrilobular nodular opacities and small patchy ground-glass opacities. These findings could indicate early lesions of ILD, but they seemed inconspicuous and nonspecific, and it might have been difficult to diagnose ILD then. To date, few cases of ILD associated with olaparib have been reported. However, based on previous reports, fever is often seen, and CT findings mainly comprise diffuse ground-glass opacities, and in some cases, centrilobular nodular shadows. Thus, in conjunction with the findings of the present case, these characteristics may be representative of olaparib-induced ILD.

Clinical course of COPD patients with exercise-induced elevation of pulmonary artery pressure or less severe pulmonary hypertension presenting with respiratory symptoms and the impact of bosentan intervention-prospective, single-center, randomized, parallel-group study.

BACKGROUND: The data on bosentan were lacking for the treatment of exercise-induced elevation of pulmonary artery pressure (eePAP) or less severe PH in COPD. This study was conducted to investigate long-term efficacy and safety of bosentan for the treatment of eePAP or less severe PH in COPD. METHODS: COPD patients diagnosed at this hospital as having COPD (WHO functional class II, III or IV) with eePAP or less severe PH whose respiratory symptoms were stable but remained and gradually progressed even after COPD therapy were randomly assigned in a 1:1 ratio to receive either bosentan or no PH treatment for two years and assessed at baseline and every 6 months for respiratory failure, activities of daily living (ADL), lung and heart functions by right heart catheterization (RHC), and other parameters. RESULTS: A total of 29 patients who underwent RHC for detail examination were enrolled in the current study between August 2010 and October 2018.No death occurred in drug-treated group (n = 14) for 2 years; 5 patients died in untreated group (n = 15). Significant differences were noted between the 2 group in hospital-free survival (686.00 ± 55.87 days vs. 499.94 ± 53.27 days; hazard ratio [HR], 0.18; P = 0.026) and overall survival (727 days vs. 516.36 ± 55.38 days; HR, 0.095; P = 0.030) in all causes of death analysis, but not in overall survival in analysis of respiratory-related death. Bosentan was not associated with increased adverse events including requiring O2 inhalation. CONCLUSIONS: This study suggested that the prognosis for COPD patients with eePAP or less severe PH presenting with respiratory symptoms was very poor and that bosentan tended to improve their prognosis and suppress ADL deterioration without worsening respiratory failure. TRIAL REGISTRATION: This study was registered with UMIN-CTR Clinical Trial as UMIN000004749 . First trial registration at 18/12/2010.

Identification of kynurenine and quinolinic acid as promising serum biomarkers for drug-induced interstitial lung diseases.

BACKGROUND: Drug-induced interstitial lung disease (DILD) is a lung injury caused by various types of drugs and is a serious problem in both clinical practice and drug development. Clinical management of the condition would be improved if there were DILD-specific biomarkers available; this study aimed to meet that need. METHODS: Biomarker candidates were identified by non-targeted metabolomics focusing on hydrophilic molecules, and further validated by targeted approaches using the serum of acute DILD patients, DILD recovery patients, DILD-tolerant patients, patients with other related lung diseases, and healthy controls. RESULTS: Serum levels of kynurenine and quinolinic acid (and kynurenine/tryptophan ratio) were elevated significantly and specifically in acute DILD patients. The diagnostic potentials of these biomarkers were superior to those of conventional lung injury biomarkers, Krebs von den Lungen-6 and surfactant protein-D, in discriminating between acute DILD patients and patients with other lung diseases, including idiopathic interstitial pneumonia and lung diseases associated with connective tissue diseases. In addition to identifying and evaluating the biomarkers, our data showed that kynurenine/tryptophan ratios (an indicator of kynurenine pathway activation) were positively correlated with serum C-reactive protein concentrations in patients with DILD, suggesting the potential association between the generation of these biomarkers and inflammation. Our in vitro experiments demonstrated that macrophage differentiation and inflammatory stimulations typified by interferon gamma could activate the kynurenine pathway, resulting in enhanced kynurenine levels in the extracellular space in macrophage-like cell lines or lung endothelial cells. Extracellular quinolinic acid levels were elevated only in macrophage-like cells but not endothelial cells owing to the lower expression levels of metabolic enzymes converting kynurenine to quinolinic acid. These findings provide clues about the molecular mechanisms behind their specific elevation in the serum of acute DILD patients. CONCLUSIONS: The serum concentrations of kynurenine and quinolinic acid as well as kynurenine/tryptophan ratios are promising and specific biomarkers for detecting and monitoring DILD and its recovery, which could facilitate accurate decisions for appropriate clinical management of patients with DILD.

Clinicopathological Characteristics of Everolimus-Associated Interstitial Lung Disease: A Single-Center Consecutive Analysis.

BACKGROUND: Everolimus, a mammalian target of rapamycin inhibitor used as an antineoplastic drug, is associated with a remarkably high incidence of interstitial lung disease (ILD). The clinical and pathological characteristics of ILD caused by everolimus have not been thoroughly investigated; therefore, we aimed to elucidate the features of everolimus-associated ILD. METHODS: We retrospectively reviewed the medical records of patients who received everolimus for cancer treatment at our hospital. Patient backgrounds were compared between the ILD and non-ILD groups. Chest computed tomography (CT), changes in biomarkers, and lung histopathological features were analyzed for ILD cases. RESULTS: Sixty-six patients were reviewed, and ILD developed in 19. There were no differences in patient demographics between the ILD and non-ILD groups. The severity of ILD was grade 1 (G1) in 9 and grade 2 (G2) in 10 cases. Chest CT showed organizing pneumonia (OP) or a hypersensitive pneumonia pattern. The levels of lactate dehydrogenase, C-reactive protein, Krebs von den lungen-6, and surfactant protein-D (SP-D) at the onset of ILD were significantly higher than those at baseline. Analysis of G1 and G2 ILD subgroups showed a higher SP-D levels in the G2 subgroup. Five patients underwent lung biopsies; all specimens demonstrated alveolitis with lymphocytic infiltration and granulomatous lesions, and some had OP findings. CONCLUSIONS: Everolimus-associated ILD is mild and has a favorable prognosis. Patients with symptomatic ILD were more likely to have higher SP-D levels than those with asymptomatic ILD. Granulomatous lesions are an important pathological feature of everolimus-associated ILD.

Smoking-Related Interstitial Fibrosis and Smoker's Macrophages.

Smoking-related interstitial lung diseases (SRILDs) are a group of heterogeneous diffuse pulmonary parenchymal diseases associated with tobacco exposure. Smoking-related interstitial fibrosis (SRIF) is relatively recent, a pathologically defined form of SRILDs. SRIF is characterized by the accumulation of macrophages in the alveolar spaces, which is associated with interstitial inflammation and fibrosis. The macrophages frequently contain light brown pigment and are called 'smoker's macrophages'. Patients with SRIF who have clinical evidence of interstitial lung disease are most commonly relatively young, heavy smokers with abnormalities on chest computed tomography showing ground-glass opacities, peripheral consolidation, and reticulation. Although SRIF is caused by cigarette smoking, the exact pathophysiological mechanisms by which smoking causes this type of interstitial fibrosis remain unknown. The degree of fibrosis and appearance of macrophage aggregates are important points of distinction when evaluating and diagnosing SRIF. Macrophage heterogeneity, particularly the activation and function of monocyte-derived alveolar macrophages (Mo-AMs) and interstitial macrophages (IMs), has important implications for the pathogenesis of SRIF and developing treatments. Further researches focused on smoker's macrophages are needed to understand of the pathogenesis of SRIF.

Age group differences in psychological distress and leisure-time exercise/socioeconomic status during the COVID-19 pandemic: a cross-sectional analysis during 2020 to 2021 of a cohort study in Japan.

Objective: This study aimed to determine the association between psychological distress and leisure-time exercise/socioeconomic status by age group, using data from a cohort study in Japan during the COVID-19 pandemic. Methods: This cross-sectional study was conducted among participants in the ME-BYO cohort, aged 20-85 years, living or working in Kanagawa, Japan. A questionnaire was disseminated to 1,573 participants (51.7% men) between December 2020 and March 2021. The questionnaire items included psychological distress (using the 6-item Kessler Psychological Distress Scale [K6]), leisure-time exercise, and socioeconomic status. Multivariate analyses were conducted using logistic regression analysis for each age group. Results: We found that 47.4% of 20-39-year-olds, 40.6% of 40-64-year-olds, and 28.3% of 65-85-year-olds experienced psychological distress (K6: ≥5 points). For those aged 20-39 years, leisure-time exercise (odds ratio [OR] (95% confidence interval) = 0.45 (0.28-0.73)) and higher annual household income [0.53 (0.32-0.90)] were associated with less psychological distress. For those aged 40-64 years, older age was associated with less psychological distress, while full-time work [1.98 (1.05-9.71)] was associated with more psychological distress. In the 65-85-year age group, higher education and higher annual income tended to be associated with less psychological distress. For those over 40 years of age, living with other(s) was associated with reduced psychological distress. Conclusion: In the general population of Japan, not engaging in leisure-time exercise and low income affect psychological distress among young adults. Further detailed studies are needed to consider overall physical activity, job type, and work style.

Clinical and imaging features of interstitial lung disease in cancer patients treated with trastuzumab deruxtecan.

BACKGROUND: Interstitial lung disease/pneumonitis (ILD/pneumonitis) has been identified as a drug-related adverse event of special interest of trastuzumab deruxtecan (T-DXd), but there were a few reports of T-DXd-related ILD/pneumonitis in clinical practice. METHODS: Between May 25, 2020 (the launch of T-DXd in Japan) and February 24, 2022, there were 287 physician-reported potential ILD/pneumonitis cases from the Japanese post-marketing all-case surveillance. By February 27, 2022, an independent adjudication committee assessed 138 cases and adjudicated 130 cases as T-DXd-related ILD/pneumonitis. The clinical features and imaging characteristics of these cases were evaluated. RESULTS: The majority of adjudicated T-DXd-related ILD/pneumonitis cases were grade 1 or 2 (100/130, 76.9%). The most common radiological pattern types observed were organizing pneumonia patterns (63.1%), hypersensitivity pneumonitis patterns (16.9%), and diffuse alveolar damage (DAD) patterns (14.6%). Eleven cases (8.5%) from 130 resulted in death; the majority of these (8/11, 72.7%) had DAD patterns. The overall proportion of recovery (including the outcomes of recovered, recovered with sequelae, and recovering) was 76.9%, and the median time to recovery was 83.5 days (interquartile range: 42.25-143.75 days). Most cases (59/71, 83.1%) that were treated with corticosteroids were considered responsive to treatment. CONCLUSIONS: This is the first report to evaluate T-DXd-related ILD/pneumonitis cases in clinical practice. Our findings are consistent with previous reports and suggest that patients with DAD patterns have poor outcomes. Evaluation of a larger real-world dataset may further identify predictors of clinical outcome.

Pulmonary manifestation of inflammatory bowel disease: Two case reports.

Pulmonary involvement associated with inflammatory bowel disease (IBD) are a rare extraintestinal manifestation (EIM) of inflammatory bowel disease (IBD), we herein presented two cases. Case 1: 53-year-old man with Crohn's disease treated with mesalazine and azathioprine. Pulmonary nodular shadows were incidentally detected on chest imaging, and revealed granulomas through transbronchial lung biopsy. Case 2: 68-year-old man with ulcerative colitis treated with mesalazine. He presented with fever and respiratory symptoms, and chest imaging showed multiple nodular infiltrates. He was diagnosed with organizing pneumonia by lung biopsy. Both cases were diagnosed to have pulmonary involvement associated with inflammatory bowel disease (IBD) according to multidisciplinary examination including positron emission tomography-computed tomography (FDG-PET) and pathological test. Pulmonary manifestations with IBD may not always require discontinuation of drugs or additional use of steroids or immunosuppressants.

Increased CTGF expression in alveolar epithelial cells by cyclic mechanical stretch: Its mechanism and the therapeutic effect of pirfenidone.

The mechanisms of fibrosis onset and development remain to be elucidated. However, it has been reported that mechanical stretch promotes fibrosis in various organs and cells, and may be involved in the pathogenesis of pulmonary fibrosis. We demonstrated that ventilator-induced lung hyperextension stimulation in mice increased the expression of connective tissue growth factor (CTGF), a profibrotic cytokine, in lung tissue. Increased CTGF expression induced by cyclic mechanical stretch (CMS) was also observed in vitro using A549 human alveolar epithelial cells. Pathway analysis revealed that the induction of CTGF expression by CMS involved MEK phosphorylation. Furthermore, early growth response 1 (Egr-1) was identified as a transcription factor associated with CTGF expression. Finally, the antifibrotic drug pirfenidone significantly reduced CTGF expression, MEK phosphorylation, and Egr-1 levels induced by CMS. Thus, our results demonstrated that profibrotic cytokine CTGF induced by CMS may be a therapeutic target of pirfenidone.

The ME-BYO index: A development and validation project of a novel comprehensive health index.

Quantifying health status and identifying modifiable factors are essential for effective and individualized prevention of age-related conditions and for promoting health during aging. The ME-BYO concept from Kanagawa Prefecture, one of Japan's largest prefectures, can be used to establish a healthy aging society. In disease etiology, ME-BYO considers the status of an individual's body and mind as changing continuously from healthy to sick instead of being a dichotomy between the two. ME-BYO conceptualizes the entire process of this change. The ME-BYO index was developed in 2019 to comprehensively and numerically measure and visualize an individual's current health status and future disease risk by quantifying data on the four domains of metabolic function, locomotor function, cognitive function, and mental resilience. The ME-BYO index has been implemented in the personal health management application "My ME-BYO." However, scientific validation of this index and the development of a practical application using healthcare data remain to be completed. In 2020, our research team started a project to refine the ME-BYO index using data from the Kanagawa ME-BYO prospective cohort study, which is a large population-based genomic cohort study. This project will scientifically evaluate the ME-BYO index and develop a practical application for promoting healthy aging.

Pulmonary sarcoidosis complicated by rheumatoid arthritis in a patient presenting with progressive fibrosing interstitial lung disease and treated with nintedanib: a case report and literature review.

Sarcoidosis is a multisystem disease with an unknown etiology and is characterized by the formation of noncaseating granulomas in the affected organs. We present the case of a 69-year-old male Japanese patient with bilateral hilar lymphadenopathy on chest radiographs for more than 10 years, left without further investigation. The patient reported no clinical symptoms. Chest computed tomography revealed ground-glass opacities and reticular shadows in both lungs, along with bilateral hilar and mediastinal lymphadenopathy. Lymphocytosis was observed in bronchoalveolar lavage fluid. Pathological examination of transbronchial lung biopsy revealed noncaseating, epithelioid granulomas congruous with sarcoidosis, together with other findings. There were no abnormalities on electrocardiogram, echocardiogram, and ophthalmic examination.For progressive dyspnea on exertion, systemic corticosteroid therapy with oral prednisolone (25 mg/day) was initiated in 2017 and gradually tapered. Despite this intervention, the decline in forced vital capacity (FVC) was accelerated. Three years later, the patient noticed swelling in his right wrist. Further investigation revealed elevated anti-cyclic citrullinated peptide antibodies and absence of noncaseating epithelioid granuloma on surgical biopsy, leading to the diagnosis of rheumatoid arthritis (RA). Thereafter, the anti-fibrotic agent nintedanib was initiated, because interstitial lung disease (ILD) was considered to have converted into a progressive fibrosing phenotype (PF-ILD) with overlapping RA-associated lung involvement. With treatment, the progression of decline in FVC was slowed, although home oxygen therapy was introduced.