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Background: Few studies have investigated fracture risk and mortality in a Japanese chronic kidney disease (CKD) stages G3–5 population using a large-scale clinical database. Methods: This retrospective cohort study extracted data from 1 April 2008 to 30 April 2023. A single age–sex-matched control without CKD was matched with each non-dialysis CKD (estimated glomerular filtration rate < 60 mL/min/1.73 m2) patient. The incidences of all and hip fractures and all-cause mortality after the index date were calculated. Results: Among 76,598 (38,299 per group) individuals matched, the incidence of all fractures did not differ between the CKD and control groups (5.7% vs 5.8%; hazard ratio [HR] 1.022 [95% confidence interval CI 0.952–1.098], P = 0.542). The CKD group had higher risk of hip fracture than the control group (incidence of hip fracture, 1.7% vs 1.3%; HR 1.415 [95% CI 1.234–1.622], P < 0.001). Multivariable regression analysis showed an increased risk for hip fracture in the CKD vs control groups, and a greater difference in this risk was observed with younger age. Osteoporosis treatment and bone mineral density (BMD) measurements were 10.0% and 5.3% in the CKD group and 4.4% and 4.4% in the control group, respectively. Mortality was also higher in the CKD group (HR 1.413 [95% CI 1.330–1.501], P < 0.001). Conclusions: Japanese patients with CKD had higher risk of hip fracture than those without. Treatment and BMD measurement for fracture are insufficient in Japanese patients with CKD, and more adequate management of fracture risk is needed. [ABSTRACT FROM AUTHOR]

Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) has been reported to reduce patients’ quality of life and impair cancer treatment by causing anticancer drug withdrawal or interruption. However, there are currently no effective methods for the prevention of CIPN. Renin–angiotensin–aldosterone system (RAAS) inhibitors may be associated with a reduced risk of developing oxaliplatin-induced peripheral neuropathy, and it would be valuable to examine whether they have the same effect on CIPN caused by other anticancer drugs. Our study explored the potential preventive effects of RAAS inhibitors on preventing paclitaxel-induced peripheral neuropathy (PIPN). Methods: An exploratory cohort study was conducted using commercially available administrative claims data on lung cancer patients treated with paclitaxel-based chemotherapy. Cumulative paclitaxel doses, RAAS inhibitor prescriptions, and incidences of PIPN were identified using patient medical records. Fine–Gray analyses with death as a competing risk were performed. A propensity score approach was applied to address the problem of confounding. Results: Patients with lung cancer who received paclitaxel-based chemotherapy were classified into users of RAAS inhibitor (n = 1320) and non-users of RAAS inhibitor (n = 4566). The doses of RAAS inhibitors in our study were similar to those commonly used to treat hypertension. The PIPN incidence was significantly lower in users of RAAS inhibitor than in the non-users of RAAS inhibitor (sub-distribution hazard ratio, 0.842; 95% confidence interval, 0.762–0.929). The result was consistent in various sensitivity analyses and important subgroup analyses. Conclusions: RAAS inhibitors at doses commonly used for hypertension were associated with a reduced incidence of PIPN in patients with lung cancer. [ABSTRACT FROM AUTHOR]

Osteoblasts produce the receptor activator of nuclear factor-kappa B ligand (RANKL) and osteoprotegerin, the inducer and the suppressor of osteoclast differentiation and activation. We previously proposed that the degradation of osteoprotegerin by lysine-specific gingipain of Porphyromonas gingivalis and neutrophil elastase is one of the mechanisms of bone resorption associated with infection and inflammation. In the present study, we found that cathepsin K (CTSK) also degraded osteoprotegerin in an acidic milieu and the buffer with a pH of 7.4. The 37 k fragment of osteoprotegerin produced by the reaction with CTSK was further degraded into low molecular weight fragments, including a 13 k fragment, depending on the reaction time. The N-terminal amino acid sequence of the 37 k fragment matched that of the intact osteoprotegerin, indicating that CTSK preferentially hydrolyzes the death domain-like region of osteoprotegerin, not its RANKL-binding region. The 13 k fragment of osteoprotegerin was the C-terminal 13 k portion within the RANKL-binding region of the 37 k fragment. Finally, CTSK restored RANKL-dependent osteoclast differentiation that was suppressed by the addition of osteoprotegerin. Collectively, CTSK is a possible positive regulator of osteoclastogenesis. [ABSTRACT FROM AUTHOR]

Long-term sequelae of the coronavirus disease (COVID-19) constitute Long COVID. Although Long COVID has been reported globally, its risk factors and effects on quality of life (QOL) remain unclear. We conducted a cross-sectional study using questionnaires and electronic medical records of COVID-19 patients who were diagnosed or hospitalized at five facilities in Japan. Responses were obtained from 285 out of 1,150 patients. More than half of the participants reported Long COVID symptoms of varying severity 1 year after COVID-19. Common sequelae included fatigue, dyspnea, alopecia, concentration problems, memory problems, sleeplessness, and joint pain, which often significantly reduced their QOL. COVID-19 severity was strongly associated with sputum production, chest pain, dyspnea, sore throat, and diarrhea, but not with fatigue, dysgeusia, anosmia, alopecia, and sleeplessness. Fatigue, dysgeusia, anosmia, alopecia, and sleeplessness affected the QOL among participants with asymptomatic or mild COVID-19 during the acute phase. Moreover, these sequelae persisted for prolonged periods. [ABSTRACT FROM AUTHOR]

Amine quantification is an important strategy in patient stratification and personalised medicine. This is because amines, including amino acids and methylarginines impact on many homeostatic processes. One important pathway regulated by amine levels is nitric oxide synthase (NOS). NOS is regulated by levels of (i) the substrate, arginine, (ii) amino acids which cycle with arginine and (iii) methylarginine inhibitors of NOS. However, biomarker research in this area is hindered by the lack of a unified analytical platform. Thus, the development of a common metabolomics platform, where a wide range of amino acids and methylarginines can be measured constitutes an important unmet need. Here we report a novel high-throughput ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) platform where ≈40 amine analytes, including arginine and methylarginines can be detected and quantified on a molar basis, in a single sample of human plasma. To validate the platform and to generate biomarkers, human plasma from a well-defined cohort of patients before and after coronary artery bypass surgery, who developed systemic inflammatory response syndrome (SIRS), were analysed. Bypass surgery with SIRS significantly altered 26 amine analytes, including arginine and ADMA. Consequently, pathway analysis revealed significant changes in a range of pathways including those associated with NOS. [ABSTRACT FROM AUTHOR]