Influence of social isolation and loneliness on the prognosis of advanced lung cancer patients: a prospective cohort study.

PURPOSE: The purpose of this study was to investigate the impact of social isolation and loneliness on the overall survival and death at home in patients with lung cancer. METHODS: This prospective cohort study was conducted in a Japanese tertiary hospital. The enrollment period was from April 2018 to March 2020. Patients with pathologically diagnosed advanced lung cancer were included in this study. The primary outcome was overall survival, whereas the secondary outcome was death at home. The exposures were social isolation and loneliness. RESULTS: A total of 211 patients were enrolled and divided into two groups and further into quartiles according to their social isolation and loneliness level, respectively. The hazard ratios of social isolation were 1.65 (95% confidence interval; 1.12 to 2.44) and 1.87 (95% confidence interval; 1.15 to 3.03) in the univariate analysis, while 1.40 (95% confidence interval; 0.92 to 2.13) in the multivariate analysis with complete case and multiple imputation. The odds ratio of death at home with social isolation was 3.47 (95% confidence interval; 1.08 to 11.1) in the multivariate analysis with multiple imputation. Loneliness was not associated with overall survival or death at home. CONCLUSIONS: Our study suggests that social isolation may be related to overall survival and death at home among patients with advanced lung cancer. More attention should be given to such patients at the time of diagnosis.

Dissection of Wnt5a-Ror2 signaling leading to matrix metalloproteinase (MMP-13) expression.

It has been shown that constitutively active Wnt5a-Ror2 signaling in osteosarcoma cell lines plays crucial roles in induced expression of matrix metalloproteinase-13 (MMP-13), required for their invasiveness; however, it remains largely unclear about the molecular basis of MMP-13 gene induction by Wnt5a-Ror2 signaling. Here we show by reporter assay that the activator protein 1 (AP1) (binding site in the promoter region of MMP-13 gene is primarily responsible for its transcriptional activation by Wnt5a-Ror2 signaling in osteosarcoma cell lines SaOS-2 and U2OS. Chromatin immunoprecipitation assays revealed that c-Jun and ATF2 are crucial transcription factors recruited to the AP1-binding site in the MMP-13 gene promoter during Wnt5a-Ror2 signaling in SaOS-2 cells. Using siRNA-mediated suppression or specific inhibitors, we also show that Dishevelled2 (Dvl2) and c-Jun N-terminal kinase are required for MMP-13 gene induction presumably via phosphorylation of c-Jun and ATF2 during Wnt5a-Ror2 signaling in SaOS-2 cells. Interestingly, Dvl2 and Rac1, but not Dvl3, are required for MMP-13 expression in SaOS-2 cells, whereas Dvl3, but not Dvl2 and Rac1, is required for its expression in U2OS cells, indicating the presence of distinct intracellular signaling machineries leading to expression of the same gene, in this case MMP-13 gene in different osteosarcoma cell lines. Moreover, we provide evidence suggesting that Wnt5a-Ror2 signaling might also be required for expression of MMP-13 gene during the development of the cartilaginous tissue.

Influence of loneliness and social isolation on the diagnosis and treatment of Japanese patients with advanced lung cancer: a prospective cohort study.

BACKGROUND: Social determinants of health (SDHs) are social factors that affect human health; loneliness and social isolation are core SDH factors. There is a possibility that SDHs are related to passive decision-making. However, few studies have evaluated SDHs, especially social isolation and loneliness, among lung cancer patients. This study aims to investigate the effects of social isolation and loneliness on the diagnosis and treatment of Japanese lung cancer patients. METHODS: This is a prospective cohort study that was conducted in a tertiary referral hospital in Japan (University Hospital Medical Information Network registration: UMIN000031810). The enrollment period was between April 2018 and March 2020. Patients with clinical and/or pathological diagnosis of lung cancer were enrolled in this study. Exposures were social isolation and loneliness, and main outcomes were diagnosis methods and whether the initial treatment involved active therapy or best supportive care (BSC). The confounding factors were defined as sex, age, smoking status, respiratory symptoms, weight loss, presentation with any symptoms, Eastern Cooperative Oncology Group (ECOG) performance status, tumor nodes metastasis (TNM) classification, driver gene mutations [i.e., epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK)], and programmed death-ligand 1 (PD-L1) tumor proportion score. RESULTS: The study enrolled 264 patients who were divided into quartiles according to their loneliness scores and into two groups according to the social isolation level. Univariate analysis, complete case analysis, and multivariate analysis with multiple imputation failed to detect significant differences in diagnostic method or initial treatment strategy according to loneliness or social isolation level. CONCLUSIONS: Physicians may not need to consider a patient's loneliness and/or social isolation when diagnosing lung cancer and selecting treatment under universal health insurance coverage. Further studies are needed to understand the influences of loneliness and social isolation on the prognosis of lung cancer patients.

A rare case of parathyroid crisis with respiratory failure successfully treated using extracorporeal membrane oxygenation.

Parathyroid crisis, which might occur during the natural history of primary hyperparathyroidism, presents fatal hypercalcemia. Although hyperparathyroidism is known to cause metastatic pulmonary calcification, parathyroid crisis with respiratory failure is rarely reported. Here, we present a case of parathyroid crisis with respiratory failure due to parathyroid adenoma. For the first 2 weeks after admission to our hospital, the patient was treated with hydration, calcium-lowering agents, dialysis and extracorporeal membrane oxygenation, with gradual improvement in her respiratory condition as blood calcium levels decreased. However, she still needed oxygen even after that. Therefore, parathyroidectomy was performed on day 48, and she no longer needed oxygen after the surgery. Chest computed tomography scan also demonstrated improvement in pulmonary calcification, although it did not completely disappear even 4 months after parathyroidectomy. Parathyroid crisis is an endocrine emergency, and its possibility should be considered in patients with respiratory failure with hypercalcemia.

Factors Influencing Social Isolation and Loneliness Among Lung Cancer Patients: A Cross-sectional Study.

BACKGROUND/AIM: Previous reviews of Social determinants of health in lung cancer patients have not examined essential factors such as social isolation and loneliness. This study aimed to explore the factors affecting social isolation and loneliness among lung cancer patients. PATIENTS AND METHODS: A cross-sectional study was conducted. Social isolation, loneliness, and the presence of dementia were measured using Japanese adaptations of the Lubben Social Network Scale, UCLA Loneliness Scale, and Life Function Evaluation for Care Provision, respectively. RESULTS: From March 2019 to March 2020, 264 patients were included. Social isolation was significantly higher for patients receiving welfare (adjusted OR=5.28, 95% CI=2.24-12.4). Loneliness was significantly higher for patients receiving welfare (beta coefficient=0.52, 95% Cl=0.13-0.90) with symptoms of dementia (beta coefficient=0.28, 95% Cl=0.03-0.54). CONCLUSION: Results showed that receiving welfare was associated with experiencing social isolation. Receiving welfare and symptoms of dementia were associated with experiencing loneliness.

Scholarly Activity Support Systems in Internal Medicine Residency Programs: A National Representative Survey in Japan.

Objective To describe the clinical research support systems in Japanese board certification programs of internal medicine and to assess the relationship between these support systems and the scholarly activities of residents. Methods In 2018, a 26-item web questionnaire was mailed to 542 points of contact of hospitals listed as certified residency programs of internal medicine in order to obtain information about the presence of a research support system and scholarly activity from 2016. We used hospital characteristic data from the Japanese Diagnostic Procedure Combination database, a national inpatient database, and the annual report of the Japanese Society of Internal Medicine. Results A total of 228 hospitals (42%) responded to the survey. There were regular research lectures in 129 hospitals (57%), protected time (time to perform research during working hours) in 53 hospitals (23%), research consultations in 175 hospitals (77%), regular journal clubs in 213 hospitals (77%), regular research conferences in 151 hospitals (66%), data warehouses in 139 hospitals (61%), and financial research support from the hospital budget in 140 hospitals (61%). A multivariate analysis showed that none of the research support systems were related to the number of conference presentations. In contrast, protected time [odds ratio (OR) 3.66, 95% confidence interval (CI) 1.43-9.39] and regular research conferences (OR 2.20, 95% CI 1.14-4.23) were related to the presence of clinical research presentations in scientific conferences hosted by residents. Conclusion Protected time and regular research conferences were related to the scholarly activity of residents in Japanese teaching hospitals.

Pleural effusion biomarkers and computed tomography findings in diagnosing malignant pleural mesothelioma: A retrospective study in a single center.

In this study, we aimed to examine the clinical value of the pleural effusion (PE) biomarkers, soluble mesothelin-related peptide (SMRP), cytokeratin 19 fragment (CYFRA 21-1) and carcinoembryonic antigen (CEA), and the utility of combining chest computed tomography (CT) findings with these biomarkers, in diagnosing malignant pleural mesothelioma (MPM). We conducted a retrospective cohort study in a single center. Consecutive patients with undiagnosed pleural effusions who underwent PE analysis between September 2014 and August 2016 were reviewed. This study included 240 patients (32 with MPM and 208 non-MPM). SMRP and the CYFRA 21-1/CEA ratio had a sensitivity and specificity for diagnosing MPM of 56.3% and 86.5%, and 87.5% and 74.0%, respectively. Using receiver operating characteristics (ROC) curve analysis of the ability of these markers to distinguish MPM from all other PE causes, the area under the ROC curve (AUC) for SMRP and the CYFRA 21-1/CEA ratio was 0.804 and 0.874, respectively. The sensitivity and specificity of SMRP combined with the CYFRA 21-1/CEA ratio were 93.8% and 64.9%, respectively. The sensitivity of the combination of SMRP, the CYFRA 21-1/CEA ratio, and the presence of Leung's criteria (a chest CT finding that is suggestive of malignant pleural disease) was 93.8%. In conclusion, the combined PE biomarkers had a high sensitivity for diagnosing MPM, although the addition of chest CT findings did not improve the sensitivity of SMRP combined with the CYFRA 21-1/CEA ratio. Combination of these biomarkers helped to rule out MPM effectively among patients at high risk of suffering MPM and would be valuable especially for old frail patients who have difficulty in undergoing invasive procedures such as thoracoscopy.