Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1007/s00520-023-08193-5

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.jiac.2024.06.015

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.alit.2024.10.007

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1007/s11523-024-01116-2

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Other Link： https://link.springer.com/article/10.1007/s11523-024-01116-2/fulltext.html

Authorship：Lead author   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.jiac.2024.04.007

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.cgh.2024.04.035

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Language：English   Publishing type：Research paper (scientific journal)  

Background Patients with chronic kidney disease (CKD) were excluded in most trials that investigated the effects of urate-lowering agents, such as febuxostat and allopurinol, in hyperuricemic patients. This exclusion leads to uncertainty regarding the efficacy of febuxostat in patients with CKD. Due to the high prevalence of hyperuricemia in patients with CKD, we aimed to assess the effect of febuxostat on improving patient outcomes concerning cardiovascular events and survival compared with those treated with allopurinol among patients with CKD. Methods We conducted a retrospective cohort study using Japanese nationwide administrative data from Jan 1, 2013, to Sep 30, 2020. Patients aged over 60 years diagnosed with CKD were included in this study if they were prescribed either febuxostat or allopurinol. The primary outcome was the occurrence of cardiovascular events including myocardial infarction, stroke, unstable angina requiring urgent revascularization, and all-cause deaths. We estimated hazard ratios (HR) and 95% CI using a Cox proportional hazard regression model adjusted for comorbidities, medications, and laboratory data. We also assessed defined starting kidney replacement therapy as a secondary endpoint treating death as a competing risk using the Fine & Gray regression model. Results A total of 21,015 patients included those with febuxostat (n=17,796) and those with allopurinol (n=3,219). The association between the type of drug and the occurrence of cardiovascular events did not show a significant difference (0.107 vs. 0.116 events per patient-year; adjusted HR 0.953, 95% CI: 0.854 to 1.062, P=0.381). Similar results were seen for all-cause deaths (0.060 vs. 0.068 events per patient-year; adjusted HR 0.877, 95% CI: 0.760 to 1.012, P=0.073). Regarding the secondary endpoint, the association between the type of drug and the timing of starting kidney replacement therapy did not show a significant difference (0.118 vs. 0.097 events per patient-year; adjusted HR 0.953, 95% CI: 0.854 to 1.062, P=0.425). Conclusion The use of febuxostat was neither associated with a decreased risk of cardiovascular events or deaths nor with the timing of starting kidney replacement therapy compared to the use of allopurinol in patients with CKD.

DOI： 10.7759/cureus.70351

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.cllc.2023.11.003

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Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media SA  

Background: Urate-lowering drugs (ULDs) have been approved for treatment of asymptomatic hyperuricemia and gout in Japan. Although serum urate levels and rates of gout onset are known to have seasonal variations, no survey results regarding the seasonality of ULD prescriptions for asymptomatic hyperuricemia and gout have been reported.

Methods: A large-scale database of medical claims in Japan filed between January 2019 and December 2022 was accessed. In addition to total size of the recorded population for each month examined, the numbers of patients every month with newly prescribed ULDs for asymptomatic hyperuricemia and gout were noted, based on the International Classification of Diseases, 10th Revision, codes E79.0 and M10.

Results: The results identified 201,008 patients with newly prescribed ULDs (median age 49.0 years, male 95.6%). Of those, 64.0% were prescribed ULDs for asymptomatic hyperuricemia and 36.0% for gout. The proportion of new ULD prescriptions was seasonal, with that significantly (p < 0.001) higher in summer (June–August) [risk ratio (RR) 1.322, 95% CI 1.218 to 1.436] and autumn (September–November) (RR 1.227, 95% CI 1.129–1.335) than in winter (December–February), whereas the proportion in spring (March–May) was not significantly different from winter. There was no significant difference after stratification by drug type (uric acid production inhibitor/uricosuric agent) or size of the medical institution, nor subgrouping by age or sex (p for interaction = 0.739, 0.727, 0.886, and 0.978, respectively). On the other hand, the proportions of new ULD prescriptions for asymptomatic hyperuricemia were significantly lower and for gout significantly higher in spring than winter, while those were similar in summer and autumn for both groups (p for interaction<0.001).

Conclusion: The present findings indicate that new prescriptions for ULDs to treat asymptomatic hyperuricemia or gout in Japan show seasonal differences, with higher rates noted in summer and autumn as compared to winter.

DOI： 10.3389/fphar.2024.1230562

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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Abstract

Alectinib is the first‐line therapy for anaplastic lymphoma kinase‐positive non‐small‐cell lung cancer. Although some guidelines have recommended using other anaplastic lymphoma kinase inhibitors after alectinib failure, evidence for such regimens in patients who fail to respond to alectinib is limited. This study involved using administrative claims data from acute care hospitals in Japan. We extracted the data of 634 patients diagnosed with lung cancer between September 1, 2014, and January 31, 2023, who received alectinib treatment before treatment with another anaplastic lymphoma kinase inhibitor. We assessed distributions of patients according to their treatment sequencing and prognosis among three periods defined based on the initial marketing dates of lorlatinib and brigatinib. The type of anaplastic lymphoma kinase inhibitors after alectinib failure changed over time. In the most recent period, lorlatinib (58%) and brigatinib (40%) became predominant. Two‐year overall survival improved over time (47%–84%), accompanied by an increased 2‐year proportion of patients who continuously used anaplastic lymphoma kinase inhibitors after alectinib failure (13%–44%). The times to treatment discontinuation of the regimen between patients treated with lorlatinib and brigatinib were similar, with a hazard ratio of 1.02 (95% confidence interval, 0.64–1.64) in the period after marketing brigatinib. This study provides insights into the evolving treatment landscape for patients with anaplastic lymphoma kinase‐positive non‐small‐cell lung cancer who experience failed alectinib treatment and highlights the need for further studies and data accumulation to determine the optimal treatment strategy.

DOI： 10.1111/cas.16056

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Xanthine oxidoreductase (XOR) inhibitor administration, known to reduce uric acid and reactive oxygen species (ROS) production, also improves vascular endothelial function (VEF). This cross-sectional study examined our hypothesis that XOR contributes to impaired VEF through ROS but not uric acid production. METHODS: In 395 subjects (196 males, 199 females) without urate-lowering agent administration who underwent a health examination, plasma XOR activity was determined using our highly sensitive assay based on [13C2,15N2] xanthine and liquid chromatography/triple quadrupole mass spectrometry. For VEF evaluation, flow-mediated dilatation (FMD) in the brachial artery was determined by ultrasound, with physical and laboratory measurements also obtained. RESULTS: The median values for plasma XOR activity, serum uric acid, and FMD were 26.6 pmol/h/mL, 5.4 mg/dL, and 6.2%, respectively. Simple regression analysis showed weak correlations of both log plasma XOR activity and serum uric acid level with FMD (r = -0.213, p < 0.001 and r = -0.139, p = 0.006, respectively). However, multivariable linear regression analyses revealed that log plasma XOR activity but not serum uric acid level remained associated with FMD (β = -0.116, p = 0.037 and β = 0.041, p = 0.549, respectively) after adjustments for various clinical parameters, with no remarkable inconsistencies for the association observed in subgroups divided based on sex or uric acid level. Finally, a series of mediation analyses showed that serum uric acid level did not meet the criteria for mediator of the association of plasma XOR activity with FMD (p = 0.538). CONCLUSIONS: These findings suggest the possibility that XOR contributes to the pathophysiology of impaired VEF through ROS but not uric acid production.

DOI： 10.1016/j.ijcha.2023.101264

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Language：English   Publishing type：Research paper (scientific journal)  

Uric acid has antioxidant properties. To examine whether a low uric acid level is associated with severe coronavirus disease 2019 (COVID-19) progression via inflammation, alveolar damage, and/or coagulation abnormality, a retrospective observational study of 488 patients with non-severe COVID-19 and serum uric acid level ≤7 mg/dL at admission was conducted. Serum C-reactive protein (CRP), serum Krebs von den Lungen 6 (KL-6), and plasma D-dimer levels were also measured as markers of inflammation, alveolar damage, and coagulation abnormality, respectively. Median values for uric acid, CRP, KL-6, and D-dimer at admission were 4.4 mg/dL, 3.33 mg/dL, 252.0 U/mL, and 0.8 µg/mL, respectively. Among the total cohort, 95 (19.5%) progressed to severe COVID-19 with a median (interquartile range) time of 7 (4-14) days. Multivariable Cox proportional hazards regression analysis showed that low uric acid level was associated with a higher rate of severe COVID-19 progression. However, uric acid level was inversely associated with CRP level, and the association between the level of uric acid and severe COVID-19 progression was significantly different with and without CRP level inclusion. In contrast, no such association was found for KL-6 or D-dimer level. Low uric acid may contribute to severe COVID-19 progression via increased inflammation in subjects without hyperuricemia.

DOI： 10.3390/biomedicines11030854

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Language：English   Publishing type：Research paper (scientific journal)  

Coronavirus disease 2019 (COVID-19) vaccination reduces the risk of progression to severe COVID-19 in the general population. To examine that preventive effect in dialysis patients, the association of vaccination status with severe COVID-19 progression was investigated in this retrospective observational study conducted from December 2020 to May 2022 of 100 such patients hospitalized for non-severe COVID-19 at Inoue Hospital (Suita, Japan). Fifty-seven were fully vaccinated, defined as receiving a COVID-19 vaccine second dose at least 14 days prior to the onset of COVID-19, while 43 were not. Among all patients, 13 (13.0%) progressed to severe COVID-19 with a median (interquartile range) time of 6 (2.5-9.5) days, while 87 (87.0%) were discharged after 11 (8-16) days. Kaplan-Meier analysis showed that fully vaccinated patients had a significantly lower rate of progression to severe COVID-19 (p = 0.001, log-rank test). Cox proportional hazard analysis also indicated that full COVID-19 vaccination was significantly associated with reduced instances of progression to severe COVID-19 (hazard ratio 0.104, 95% confidence interval 0.022 to 0.483; p = 0.004) after balancing patient background characteristics using an inverse probability of treatment weight method. These results suggest that full vaccination status contributes to reducing the risk of progression from non-severe to severe COVID-19 in dialysis patients.

DOI： 10.3390/jcm11216348

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J-GLOBAL

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Event date： 2023.11

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Event date： 2023.6

Language：Japanese  

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Event date： 2023.2

Language：Japanese  

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Event date： 2022.12

Language：Japanese  

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Event date： 2022.9

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