👤 Rina Onishi

Hospitalization-associated disability (HAD) is linked to poor post-discharge outcomes in older individuals with heart failure (HF). We investigated whether HAD could be predicted by physical activity measured using a wearable device. We retrospectively analyzed data from 104 older individuals with HF whose physical activity was recorded for 3 consecutive days after initiating cardiac rehabilitation. Physical activity was categorized as sedentary behavior (≤1.5 metabolic equivalents [METs]), light-intensity physical activity (LPA; 1.6-2.9 METs), and moderate-to-vigorous physical activity (≥3.0 METs). HAD was observed in 31 (29.8%) individuals. LPA duration was significantly shorter in the HAD than non-HAD group (mean [±SD] 45.7±24.9 vs. 121.2±67.4 min/day; P<0.0001). In receiver operating characteristic curve analysis, the optimal LPA cut-off was 68 min/day, with 87.1% sensitivity and 80.8% specificity (area under the curve=0.888; P<0.0001). Physical activity measured using a wearable device may be useful in predicting HAD in older individuals with HF. Show less

Hepatocellular carcinoma (HCC) arises from various etiologies, including viral hepatitis and non-viral liver diseases. Although comprehensive genomic profiling (CGP) is increasingly applied in oncology, the influence of disease etiology on the genomic landscape of HCC and biomarker applicability remains insufficiently characterized. CGP data from 551 patients with HCC, registered in the National Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database, were analyzed after excluding cases with undefined etiology. We characterized the mutational landscape, compared mutation frequencies among HBV-, HCV-, and non-viral, non-cholestatic (nBnC)-related HCC, assessed the association between homologous recombination repair (HRR)-related gene alterations and tumor mutation burden (TMB), and evaluated the detection rates of actionable mutations in tissue- versus liquid-based CGP. Telomerase reverse transcriptase splice site mutations were the most common genomic alteration and were consistently observed across all etiologic groups. Although mutations in AXIN1 and DDR2 genes showed modest enrichment in HCV- and HBV-related HCC, respectively, the overall mutational profiles remained largely conserved across etiologies. TMB was significantly lower in nBnC-HCC compared to HCV-related HCC but showed no association with HRR-related mutations. The detection rates of targetable mutations were similar between tissue and liquid biopsies; however, only a small proportion of patients received matched therapies. Real-world data indicate a conserved genomic architecture in HCC regardless of etiology, supporting unified therapeutic approaches. The absence of a relationship between HRR alterations and TMB suggests distinct biological mechanisms. Liquid biopsy remains a reliable option when tissues are unavailable in managing patients with HCC. Show less

AA amyloidosis is a rare renal complication of Waldenström's macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL). A 66-year-old man with WM/LPL presented with nephrotic syndrome. A renal biopsy showed AA amyloidosis. Chemotherapy resulted in the remission of hematologic and nephrotic syndromes. Two years into follow-up, he became infected with coronavirus disease 2019 and had massive proteinuria, despite no relapse of WM/LPL. A second renal biopsy confirmed a diagnosis of AA amyloidosis. However, increased prednisolone did not improve proteinuria. The patient ultimately died of cryptococcal meningitis. This case highlights the diverse spectrum of renal involvement in monoclonal IgM-secreting diseases and difficulty in managing fatal complications. Show less

Tamoxifen is a potent antagonist of estrogen, and hepatic steatosis is a frequent complication in adjuvant tamoxifen for breast cancer. Impaired hepatic FA beta-oxidation in peroxisomes, microsomes, and mitochondria results in progression of massive hepatic steatosis in estrogen deficiency. This impairment, although latent, is potentially serious: About 3% of the general population in the United States is now suffering from nonalcoholic steatohepatitis associated with obesity and hyperlipidemia. Therefore, in the present study we tried to restore impaired hepatic FA beta-oxidation by administering a novel statin, pitavastatin, to aromatase-deficient (Ar-/-) mice defective in intrinsic estrogen synthesis. Northern blot analysis of Ar-/- mice liver revealed a significant restoration of mRNA expression of essential enzymes involved in FA beta-oxidation such as very long fatty acyl-CoA synthetase in peroxisome, peroxisomal fatty acyl-CoA oxidase, and medium-chain acyl-CoA dehydrogenase. Severe hepatic steatosis observed in Ar-/- mice substantially regressed. Consistent findings were obtained in the in vitro assays of FA beta-oxidation activity. These findings demonstrate that pitavastatin is capable of restoring impaired FA beta-oxidation in vivo via the peroxisome proliferator-activated receptor-alpha-mediated signaling pathway and is potent enough to ameliorate severe hepatic steatosis in mice deficient in intrinsic estrogen. Show less