Background: Standard therapy for cancer-associated venous thromboembolism (VTE) is low-molecular-weight heparin. The use of direct oral anticoagulants for cancer-associated VTE has increased; however, their efficacy and safety in lung cancer patients remain unclear. Objectives: We examined the efficacy and safety of rivaroxaban compared with dalteparin for cancer-associated VTE in patients with primary lung cancer. Methods: A single-center retrospective study of 204 patients with primary lung cancer who were prescribed rivaroxaban (n = 131) or dalteparin (n = 73) for VTE was performed. The primary endpoint was a composite event including recurrence and major or clinically relevant nonmajor bleeding. Secondary endpoints included the incidence of recurrence, major and clinically relevant nonmajor bleeding, all-cause mortality, and bleeding or pulmonary embolism-related mortality. Results: The composite event occurred in 38 (29.0) and 12 (16.4%) patients in the rivaroxaban and dalteparin (p = 0.045) groups, respectively. The multivariate Cox proportional hazards model for age, Eastern Cooperative Oncology Group performance score, and bleeding risk factors revealed the rivaroxaban group showed a 1.176-fold composite event risk without statistical significance (0.595–2.324, p = 0.641). There was no statistically significant intergroup difference for the incidence of VTE recurrence (5.3% in the rivaroxaban group versus 2.7% in the dalteparin group, p = 0.495) and major or clinically relevant nonmajor bleeding (23.7% in the rivaroxaban group versus 13.7% in the dalteparin group, p = 0.089). There was no significant difference in the all-cause mortality rate (hazard ratio 0.864, 95% CI 0.624–1.196, p = 0.337). Conclusions: There was no difference in the safety and efficacy profile of rivaroxaban compared with dalteparin. Therefore, rivaroxaban may be a valuable treatment option for lung cancer-associated VTE.

Purpose Although osimertinib is the standard-of-care treatment of epidermal growth factor receptor (EGFR) T790M mutation–positive non–small cell lung cancer, real-world evidence on the efficacy of osimertinib is not enough to reflect the complexity of the entire course of treatment. Herein, we report on the use of osimertinib in patients with EGFR T790M mutation–positive non–small cell lung cancer who had previously received EGFR tyrosine kinase inhibitor (TKI) treatment in Korea.Materials and Methods Patients with confirmed EGFR T790M after disease progression of prior EGFR-TKI were enrolled and administered osimertinib 80 mg daily. The primary effectiveness outcome was progression-free survival, with time-to-treatment discontinuation, treatment and adverse effects leading to treatment discontinuation, and overall survival being the secondary endpoints.Results A total of 558 individuals were enrolled, and 55.2% had investigator-assessed responses. The median progression-free survival was 14.2 months (95% confidence interval [CI], 13.0 to 16.4), and the median time-to-treatment discontinuation was 15.0 months (95% CI, 14.1 to 15.9). The median overall survival was 36.7 months (95% CI, 30.9 to not reached). The benefit with osimertinib was consistent regardless of the age, sex, smoking history, and primary EGFR mutation subtype. However, hepatic metastases at the time of diagnosis, the presence of plasma EGFR T790M, and the shorter duration of prior EGFR-TKI treatment were poor predictors of osimertinib treatment. Ten patients (1.8%), including three with pneumonitis, had to discontinue osimertinib due to severe adverse effects.Conclusion Osimertinib demonstrated its clinical effectiveness and survival benefit for EGFR T790M mutation–positive in Korean patients with no new safety signals.

Two randomized, controlled studies comparing outcomes in patients treated with direct oral anticoagulants or low-molecular weight heparin for cancer-associated venous thromboembolism (VTE) have previously been performed. However, gynecologic cancers accounted for approximately 10% of the study populations. We compared the outcomes of patients with primary gynecological cancers who were treated for cancer-associated VTE with either rivaroxaban or dalteparin. The 162 eligible patients with gynecologic cancers who were treated with either dalteparin (n=60) or rivaroxaban (n=102) were reviewed. The primary outcome was a composite event, which included recurrence or clinically relevant bleeding events during the therapeutic period. Secondary outcomes were recurrence, clinically relevant bleeding events, and mortality. During the therapeutic period, there were no significant differences between the groups in the proportion of composite events, recurrence, or clinically relevant bleeding. Multivariate analysis using the Cox proportional hazards model also showed no significant difference in the number of composite events and clinically relevant bleeding between the groups. In the rivaroxaban group, 44.0% of patients experienced gastrointestinal bleeding and 24.0% experienced urinary tract bleeding. In the dalteparin group, bleeding was most common in the urinary tract (44.4%) and at the injection site (22.2%). In this study, although there were no significant differences in effectiveness or safety between the rivaroxaban and dalteparin groups, rivaroxaban use was associated with a higher rate of clinically relevant bleeding than dalteparin. Therefore, caution should be taken when prescribing rivaroxaban for gynecologic cancer-associated VTE and bleeding events should be carefully monitored.

Drosophila melanogaster expressing amyloid-β42 (Aβ42) transgenes have been used as models to study Alzheimer’s disease. Various Aβ42 transgenes with different structures induce different phenotypes, which make it difficult to compare data among studies which use different transgenic lines. In this study, we compared the phenotypes of four frequently used Aβ42 transgenic lines, UAS-Aβ42^2X, UAS-Aβ42^BL33770, UAS-Aβ42^11C39, and UAS-Aβ42^H29.3. Among the four transgenic lines, only UAS-Aβ42^2X has two copies of the upstream activation sequence-amyloid-β42 (UAS-Aβ42) transgene, while remaining three have one copy. UAS-Aβ42^BL33770 has the 3′ untranslated region of Drosophila α-tubulin, while the others have that of SV40. UAS-Aβ42^11C39 and UAS-Aβ42^H29.3 have the rat pre-proenkephalin signal peptide, while UAS-Aβ42^2X and UAS-Aβ42^BL33770 have that of the fly argos protein. When the transgenes were expressed ectopically in the developing eyes of the flies, UAS-Aβ42^2X transgene resulted in a strongly reduced and rough eye phenotype, while UAS-Aβ42^BL33770 only showed a strong rough eye phenotype; UAS-Aβ42^H29.3 and UAS-Aβ42^11C39 had mild rough eyes. The levels of cell death and reactive oxygen species (ROS) in the eye imaginal discs were consistently the highest in UAS-Aβ42^2X, followed by UAS-Aβ42^BL33770, UAS-Aβ42^11C39, and UAS-Aβ42^H29.3. Surprisingly, the reduction in survival during the development of these lines did not correlate with cell death or ROS levels. The flies which expressed UAS-Aβ42^11C39 or UAS-Aβ42^H29.3 experienced greatly reduced survival rates, although low levels of ROS or cell death were detected. Collectively, our results demonstrated that different Drosophila AD models show different phenotypic severity, and suggested that different transgenes may have different modes of cytotoxicity. Abbreviations: Aβ42: amyloid-β42; AD: Alzheimer’s disease; UAS: upstream activation sequence

Purpose: Pulmonary rehabilitation (PR) is a well-established treatment for chronic obstructive pulmonary disease (COPD). The standard protocol for PR requires frequent hospital visits, which can be difficult for patients. We performed this study to assess whether unsupervised home-based PR (HBPR) is effective for patients with COPD. Patients and Methods: After assessing the outcome data, including the results of a COPD assessment test (CAT); the body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index; a spirometry; the modified Medical Research Council (mMRC) dyspnea scale; and the 6-min walking test (6MWT), specialists imparted 1-hour education to patients regarding unsupervised HBPR at the baseline visit. This included methods for breathing, inhaler use, stretching, and exercise. On reviewing diaries after 8 weeks from the first visit, patients who exercised at least thrice per week were classified as the compliant group and the others were categorized as the noncompliant group. Changes in the outcomes were compared between the compliant and noncompliant groups. Results: A total of 41 patients were enrolled in this study; for 8 weeks of unsupervised HBPR, there were significant improvements in CAT scores (− 4.62± 4.61 vs 2.40± 6.73; P=0.002), BODE index (− 1.00± 1.06 vs − 0.20± 0.56; P=0.01), and forced expiratory volume in 1 s (0.05± 0.19 vs − 0.09± 0.16; P=0.02) among patients in the compliant group, compared with the noncompliant group. Moreover, their CAT (16.46± 7.80 vs 11.85± 7.23; P=0.03) and mMRC scores (2.54± 0.76 vs 1.81± 0.63; P=0.001) improved significantly after 8 weeks, compared with those at baseline. On the other hand, patients in the noncompliant group showed no significant improvement in any of the outcomes. Conclusion: In this study, compliant patients with unsupervised HBPR achieved favorable outcomes in 8 weeks. Thus, we recommend unsupervised HBPR for patients with COPD, even when regular hospital visits for PR are not possible. Trial Registration: NCT03754881.

During the treatment of Mycobacterium avium complex pulmonary disease (MAC-PD), ethambutol or rifampin is often discontinued because of adverse events. This study investigated the treatment outcomes when later-generation fluoroquinolones replace ethambutol or rifampin in MAC-PD treatment based on the radiologic type.