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

Objectives To determine the clinical features and trends of occurrence of bilirubin encephalopathy in preterm infants (pBE) in Japan. Methods We conducted a third retrospective nationwide questionnaire-based survey (2024) on pBE in Japan. We performed a two-step questionnaire survey similar to the previous two nationwide surveys. The initial survey determined the number of children born after 2000 who were newly diagnosed with pBE after the 2021 survey. Using a structured questionnaire, the secondary survey clarified the clinical manifestations and characteristics of children with pBE, including demographic data, neurological symptoms, and magnetic resonance imaging (MRI) and auditory brainstem response (ABR) findings. Results were then compared between the three surveys (2017, 2021, and 2024). Results An initial survey identified 11 patients with pBE from six institutions. After excluding one patient included in previous studies, clinical information was collected from 10 patients (six boys and four girls) during the secondary survey. The median gestational age was 27 weeks and the median birth weight was 1028 g. Head control and functional gait were observed in 50% and 20% of the patients, respectively. Purposeful hand use and verbal communication were observed in 30% and 40% of patients, respectively. MRI showed T2 hyperintensities in the globus pallidus in nine of nine patients. ABR abnormalities were present in four of four patients. None of the variables differed significantly between the 2017, 2021, and 2024 surveys. Conclusions The clinical characteristics of pBE were consistent across the three surveys. Infants with pBE had severely impaired gross motor function but relatively preserved manual function and verbal communication. MRI and ABR findings can aid in the diagnosis of pBE.

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.

Abstract Backgrounds and objectives Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare lung disorder, and its long-term clinical outcomes, underlying determinants, and temporal dynamics of serum autoantibody levels remain poorly characterized. Methods This single-center retrospective observational study comprised 64 patients diagnosed with aPAP, all of whom had been monitored for a minimum of three years following disease onset. Clinical courses were evaluated using disease severity score (DSS), based on arterial oxygen tension and respiratory symptoms. Serum anti–granulocyte-macrophage colony-stimulating factor (GM-CSF) IgG autoantibody (αGM) levels were quantified by enzyme-linked immunosorbent assay. Results Among 64 patients with any DSS, 45.3% showed clinical improvement, 40.6% remained stable, and 14.1% experienced deterioration over median follow-up period of 7.8 years. In a binary logistic regression analysis excluding patients with an initial DSS of 1, for whom improvement was not feasible, higher initial DSS, higher baseline % forced vital capacity, and the absence of fibrotic patterns on computed tomography were identified as significant explanatory variables associated with DSS improvement, whereas whole lung lavage (WLL) and GM-CSF inhalation were not in the comparison of the initial and final DSS. Longitudinal assessment of serum αGM levels in 52 patients revealed a decline in 98% of them (n = 51) with an estimated antibody half-life of 3.5 years. GM-CSF inhalation therapy was significantly associated with lower final antibody levels adjusted for initial level and the interval between the initial and final measurements by analysis of covariance. Conclusions The overall decline in αGM levels observed in this study may suggest a favorable or stable long-term prognosis in aPAP; however, further longitudinal investigations are warranted to confirm this presumed association.