Atherosclerosis and osteoporosis are epidemiologically linked and oxidation specific epitopes (OSEs), such as phosphocholine (PC) of oxidized phospholipids (PC-OxPL) and malondialdehyde (MDA), are pathogenic in both. The proatherogenic effects of OSEs are opposed by innate immune antibodies. Here we show that high-fat diet (HFD)-induced bone loss is attenuated in mice expressing a single chain variable region fragment of the IgM E06 (E06-scFv) that neutralizes PC-OxPL, by increasing osteoblast number and stimulating bone formation. Similarly, HFD-induced bone loss is attenuated in mice expressing IK17-scFv, which neutralizes MDA. Notably, E06-scFv also increases bone mass in mice fed a normal diet. Moreover, the levels of anti-PC IgM decrease in aged mice. We conclude that OSEs, whether produced chronically or increased by HFD, restrain bone formation, and that diminished defense against OSEs may contribute to age-related bone loss. Anti-OSEs, therefore, may represent a novel therapeutic approach against osteoporosis and atherosclerosis simultaneously.

The purpose of the present study was to report cases of epidermal growth factor receptor‑tyrosine kinase inhibitor (EGFR‑TKI)‑naïve patients carrying a mutation associated with acquired resistance to the drug. Gene alterations in 77 lung carcinoma patients were analyzed by collecting and studying curette lavage fluid at the time of diagnosis. PCRs were performed to amplify mutation hotspot regions in EGFR genes. The PCR products were direct‑sequenced and the mutations confirmed by resequencing using different primers. Case 1 was a 78‑year‑old Japanese male diagnosed with stage IB lung adenocarcinoma who was found to have two EGFR mutations, G719S and L747S. Case 2 was a 73‑year‑old Japanese male diagnosed with stage IV squamous cell lung carcinoma and bone metastasis who had the EGFR mutation, L747S. Case 3 was an 82‑year‑old Japanese male diagnosed with hyponatremia due to inappropriate secretion of antidiuretic hormone and stage IIIB small cell lung carcinoma (SCLC) who had the EGFR mutation, L747S. Thus, the EGFR mutation L747S associated with acquired EGFR‑TKI resistance was detected in two non‑small cell lung carcinoma (NSCLC) patients and one SCLC patient, none of whom had ever received EGFR‑TKI. The patients were current smokers with stages at diagnosis ranging from IB to IV, and their initial tumors contained resistant clones carrying L747S. L747S may be associated with primary resistance. To the best of our knowledge, this study is the first report of an EGFR mutation associated with resistance to EGFR‑TKI in SCLC patients. The early detection of EGFR‑TKI resistance mutations may be beneficial in making treatment decisions for lung carcinoma patients, including those with SCLC.

Background: Patients with chronic obstructive pulmonary disease (COPD) are more inclined to have a high level of social vulnerability due to their physical and psychological burden. However, to date, there have been no study on social frailty in patients with COPD. This study aimed to investigate the prevalence, characteristics, and impact of social frailty in patients with COPD. Methods: Social frailty was assessed using five items in a questionnaire. A patient was diagnosed with social frailty if responses to two or more items were positive. Four hundred and five patients with COPD were assessed for social frailty, dyspnea, and appetite. We also prospectively examined the number of acute exacerbation and unexpected hospitalization for 1 year. Results: Thirty-six percent of patients with COPD had social frailty. They had reduced appetite and more severe dyspnea [Simplified Nutritional Appetite Questionnaire score: odds ratio (OR) 0.81, 95% confidence interval (CI) 0.69‒0.95, p < 0.01; modified Medical Research Council score: OR 1.42, 95% CI 1.05‒1.93, P = 0.02] than patients without social frailty. Social frailty was not a risk factor for moderate acute exacerbation of COPD but a risk factor for severe acute exacerbation and all-cause unexpected hospitalization (severe acute exacerbation: β, standardized regression coefficient: 0.13, 95% CI 0.01‒0.25, P = 0.04, unexpected hospitalization: β 0.17, 95% CI 0.05‒0.29, P = 0.01). Conclusion: The prevalence of social frailty is 36%; however, social frailty has a marked clinical impact in patients with COPD.

We herein report a case of squamous cell transformation combined with the epidermal growth factor receptor (EGFR) mutation T790M associated with acquired resistance to EGFR tyrosine kinase inhibitors (EGFR‑TKIs) in a 73‑year‑old male patient diagnosed with stage IVA lung adenocarcinoma. Gene alterations were analyzed by collecting and studying pleural effusion at the time of diagnosis. Examination revealed an exon 19 deletion in the EGFR gene. Following treatment with the second‑generation EGFR‑TKI afatinib, squamous cell carcinoma was identified by performing a re‑biopsy of the recurrent site. Although the levels of cytokeratin 19 fragment, which is a tumor marker for the follow‑up of squamous cell carcinoma, were increased at that point, the levels of carcinoembryonic antigen, a marker particularly associated with adenocarcinoma, remained within normal limits. The T790M mutation and the original exon 19 deletion were detected simultaneously. The patient received treatment with the third‑generation EGFR‑TKI osimertinib, achieving a good clinical response. These findings suggest that osimertinib is beneficial for lung adenocarcinoma patients with squamous cell transformation harboring the T790M mutation.

Background: Optimal timing for treatment initiation in Mycobacterium avium complex pulmonary disease (MAC-PD) remains unclear due to lack of established rules for predicting treatment response. Methods: A retrospective observational study was conducted to develop a prediction model for treatment failure at 2 Japanese university hospitals between 2012 and 2023. Participants were 135 patients with MAC-PD who received macrolides and ethambutol-containing regimens over 1 year. Treatment failure was defined as nonachievement culture conversion at 1 year. We selected model components as cavity (categorized by diameter) and bronchiectasis (categorized by modified Reiff score) on pretreatment computed tomography. Their combinations of each category were scored based on number of lobes involved and compared by average areas under the curve calculated using k-fold cross-validation. Results: Forty-three (31.9%) of the 135 patients failed in treatment. Number of lobes with cavities > 2cm or bronchiectasis with varicose or cystic changes was designated as the prediction model, with an average area under the curve of 0.798, and was named the Bronchiectasis and Cavity Distribution score. The representative metrics were sensitivity of 0.907 at the cutoff of 2 and specificity of 0.913 at the cutoff of 4 points. The patients were stratified into low-risk (0–1 points), intermediate-risk (2–3 points), and high-risk (4–6 points) groups. The treatment failure rates were 8.0%, 35.6%, and 69.2% in the respective groups. Conclusions: With simple assessment of computed tomography findings, the Bronchiectasis and Cavity Distribution score predicted treatment failure. Although validation studies are warranted, this score may provide guidance for treatment of MAC-PD.