爱知医科大学

Abstract We analyzed the impact of the diagnosis-to-treatment interval (DTI) on survival in patients with CD5-positive diffuse large B-cell lymphoma (CD5 + DLBCL), using a data set of newly diagnosed patients. Among the 336 eligible patients, 247 (74%) received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone), and 89 (26%) were treated with dose-adjusted (DA)-EPOCH-R (etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin, and rituximab). The median DTI was 18 days (range 0–118). The short DTI (≤ 14 days) group included 135 patients (40%), and the long DTI (> 14 days) group included 201 patients (60%). Compared with the long DTI group, the short DTI group had more aggressive disease characteristics. Both the progression-free survival (PFS) (P = 0.01) and the overall survival (OS) (P < 0.01) were significantly inferior in the short DTI group compared with those in the long DTI group. Among 89 patients who received DA-EPOCH-R, no significant differences in PFS (P = 0.92) or OS (P = 0.86) were observed between the two groups. Multivariate analysis revealed that no DA-EPOCH-R was a risk factor for PFS in the short DTI group (P = 0.06). A short DTI was a negative prognostic factor in our CD5 + DLBCL cohort. DA-EPOCH-R could be considered a potential treatment option for patients with a short DTI.

This study examined changes in practice patterns and outcomes of allogeneic hematopoietic cell transplantation (HCT) over the past 20 years. Data were analyzed from a Japanese nationwide registry of consecutive adult patients with acute myeloid leukemia who underwent allogeneic HCT between 2001 and 2020. The study population included 17,553 patients, of whom 6653 underwent allogeneic HCT in 2001–2010 and 10,900 in 2011–2020. Patients in the later period were older, were more likely to be in first complete remission, and more frequently received umbilical cord blood transplantation. After adjusting for major covariates, the 2011–2020 cohort had lower risks of overall mortality (hazard ratio [HR], 0.84; 95

Background: Although the COVID-19 pandemic has impacted the management of acute coronary syndrome (ACS), the prognostic implications for ACS patients with concurrent COVID-19 undergoing percutaneous coronary intervention (PCI) remain to be determined, particularly in large nationwide cohorts. This study investigated the association between concomitant COVID-19 and clinical outcomes in patients undergoing emergent PCI for ACS. Methods and Results: This retrospective cohort study utilized data from the Japanese Percutaneous Coronary Intervention (J-PCI) nationwide registry, encompassing all patients presenting with ACS who underwent primary or emergent PCI between January 2021 and December 2023. Multivariable logistic regression models were employed to ascertain the independent association between COVID-19 positivity and in-hospital all-cause and cardiovascular mortality. The analysis included 279,662 ACS patients, of whom 1,812 (0.65%) tested positive for COVID-19. After multivariable adjustment, COVID-19 remained an independent predictor of in-hospital all-cause mortality (adjusted odds ratio [aOR] 1.46; 95% confidence interval [CI] 1.21-1.77). The association between COVID-19 and cardiovascular mortality was significant in univariable analysis but not after multivariable adjustment (aOR 1.22; 95% CI 0.98-1.52). Conclusions: In this nationwide cohort, concomitant COVID-19 was independently associated with higher in-hospital all-cause mortality among patients with ACS undergoing PCI. These findings highlight the need for heightened surveillance and consideration of tailored therapeutic strategies in this high-risk population.

Pleural mesothelioma (PM) is an uncommon yet deadly cancer linked to asbestos exposure. The lack of effective early diagnosis and treatment leads to reduced life expectancy among patients with PM. This study aims to identify a novel molecular target inhibitor to develop more effective therapeutics for PM. Our drug screening assay showed that the fatty acid synthase (FASN) inhibitor cerulenin demonstrates strong and selective antiproliferative properties against NF2/CDKN2A(p16)-deficient PM cells, surpassing the effects of C75, cisplatin or pemetrexed. FASN protein is frequently detected in NF2/p16-deficient PM tumor-derived tissues (15/15, 100%), but rarely in NF2/p16-intact PM tumors (8/25, 32%). Notably, cerulenin administration successfully reduced the growth of NF2/p16-deficient PM tumors in xenografted mice. Cerulenin inhibits mitochondrial fission by targeting dynamin-related protein 1 (DRP1) in NF2/p16-deficient cells. Moreover, the disruption of the FASN gene leads to increased ubiquitination of DRP1. These findings suggest that FASN might play a role in the tumorigenesis of PM cells through the regulation of mitochondrial dynamics. This research offers a novel perspective on the potential development of precision medicine for PM.