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
AIMS:Obesity, a risk factor for atherosclerosis development and progression, is marked by excessive reactive oxygen species (ROS) production. We previously demonstrated that high-glucose (HG) conditions induce mitochondrial ROS (mtROS) production in aortic endothelial cells (ECs). However, the link between elevated mtROS levels in obesity and atherosclerosis progression remains unclear. This study aimed to investigate whether endothelial-specific mtROS suppression by overexpressing manganese superoxide dismutase (MnSOD) could attenuate atherosclerosis progression in high-fat diet (HFD)-induced obese apolipoprotein E-deficient (ApoE KO) mice. RESULTS:Atherosclerotic lesion formation did not differ significantly between normal chow-fed control ApoE KO mice and endothelial cell-specific MnSOD-overexpressing ApoE KO (eMnSOD-Tg/ApoE KO) mice. However, in HFD-fed groups, eMnSOD-Tg/ApoE KO mice exhibited reduced atherosclerotic lesion size, decreased relative ROS levels, and lower Icam1 and Ccl2 expression compared to HFD-fed control ApoE KO mice. In obese ApoE KO mice, serum glucose, lipopolysaccharide (LPS), and low-density lipoprotein (LDL) levels were elevated. In human aortic endothelial cells, exposure to LPS, oxidized LDL, and high glucose increased relative mtROS levels, which was effectively attenuated by MnSOD overexpression. MnSOD also suppressed intercellular adhesion molecule-1 and monocyte chemoattractant protein-1 expression under these conditions. INNOVATION:Our findings demonstrate that endothelial-specific MnSOD overexpression suppresses obesity-related atherosclerosis in ApoE KO mice. CONCLUSION:mtROS plays a pivotal role in obesity-associated atherosclerosis, and targeting endothelial mtROS may offer a therapeutic strategy for preventing vascular complications in obesity. Antioxid. Redox Signal. 45, 63-77.
This study aimed to identify patient groups in which myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC) regimens induced superior progression-free survival (PFS) in patients with acute myeloid leukemia (AML) in complete remission (CR) using a machine-learning approach. Our study included 3273 patients aged 40–69 with AML in CR. The patients were divided into training (N = 2020) and validation cohorts (N = 1253). We employed a machine learning-based group identification model in the training cohort. Subsequently, in the validation cohort, we estimated the impact of the optimal conditioning group compared with the non-optimal conditioning group on PFS using an inverse probability weight analysis. The developed model was consistent with the eight factors and combinations, and the high score suggested that RIC was more appropriate than MAC. In the validation cohort, 127 patients with high scores and who received RIC and 769 patients with low scores and who received MAC were categorized into the optimal conditioning group (896, 71.5
The impact of chronic kidney disease (CKD) stage on outcomes after percutaneous coronary intervention (PCI) for left main (LM) coronary artery disease remains unclear. We investigated the impact of CKD stage on long-term outcomes after contemporary LM-PCI. We analyzed 756 consecutive patients who underwent LM-PCI for de novo lesion under intracoronary imaging-guidance across 19 hospitals. Patients were categorized by CKD stage: I/II (n = 360), IIIa (n = 212), IIIb (n = 105), IV (n = 40), and V (n = 39). Three-year major adverse cardiovascular and cerebrovascular events (MACCE), including all-cause death, clinically driven revascularization, myocardial infarction, and cerebrovascular events, were evaluated. Patients with CKD stage IIIb or worse had higher comorbidity burdens than those with CKD I/II, including high age, hypertension, peripheral artery disease, and reduced left ventricular ejection fraction. Patients with CKD-IIIb and -IV presented more acute coronary syndrome and required mechanical circulatory support, whereas these frequencies in CKD-V were similar as in CKD-I/II. In contrast, CKD V patients exhibited greater lesion complexity, with more true bifurcation lesion and calcified lesions needing atherectomy. MACCE rates were significantly higher in CKD IV and V (CKD-I/II: 28.9%, IIIa: 31.3%, IIIb: 35.7%, IV: 45.8%, V: 48.7%). All-cause mortality rose stepwise with worsening CKD (CKD-I/II: 8.4%, IIIa: 14.9%, IIIb: 24.2%, IV: 34.9%, V: 34.6%). Clinically driven revascularization rates did not increase with advancing CKD stage. In conclusion, advanced CKD was associated with progressively worse clinical outcomes after contemporary LM-PCI, primarily driven by increased mortality, whereas clinically driven revascularization did not increase with CKD severity despite greater lesion complexity.
