Abstract Introduction Dotinurad is a newer urate-lowering agent that selectively inhibits urate transporter 1 in the renal proximal tubule and increases urinary urate excretion. Currently, little is known about the clinical efficacies of dotinurad in patients with hyperuricemia and hypertension. The aim of this study was to assess the clinical effects of a selective urate reabsorption inhibitor dotinurad on serum uric acid (SUA) levels and relevant vascular markers in patients with hyperuricemia and treated hypertension. Methods This investigator-initiated, multicenter, prospective, single-arm, open-label, exploratory clinical trial in Japan enrolled patients with hyperuricemia and treated hypertension who received a 24-week dotinurad therapy (a starting dose at 0.5 mg once daily and up-titrated to 2 mg once daily). The primary endpoint was a percentage change in the SUA level from baseline to week 24. The secondary endpoints were cardiovascular and metabolic measurements, including changes in the cardio-ankle vascular index (CAVI) and derivatives of reactive oxygen metabolites (d-ROMs) concentration at week 24. Results Fifty patients (mean age 70.5 ± 11.0 years, with 76.0% being men, and mean SUA level 8.5 ± 1.2 mg/dL) were included in the analysis. The percentage change from baseline in the SUA level at week 24 was − 35.8% (95% confidence interval [CI] − 39.7% to − 32.0%, P < 0.001), with approximately three quarters of patients achieving an SUA level of ≤ 6.0 mg/dL at week 24. The proportional changes from baseline in the geometric mean of CAVI and d-ROMs at week 24 were 0.96 (95% CI 0.92 to 1.00, P = 0.044) and 0.96 (95% CI 0.92 to 1.00, P = 0.044), respectively. Conclusion In addition to meaningful SUA-lowering effects, 24 weeks of dotinurad therapy may favorably affect arterial stiffness and oxidative stress markers, suggesting off-target vascular protection of dotinurad. Further research is expected to verify our findings and elucidate the entire off-target effects of dotinurad. Trial registration jRCTs021210013, registration date June 24, 2021
Advances and improvements in cancer diagnosis and treatment have made it possible to find multiple primary cancers. We report here a rare case of metachronous quintuple cancer involving the stomach, rectum, colon, liver and prostate. An 80s‒ year‒old male was referred to our hospital with abnormality on upper GI series. He had undergone a distal gastrectomy in May 2005. Postoperative diagnosis was advanced gastric cancer (pT2N1M0, pStage ⅡA). In August 2006, anterior resection was performed with a diagnosis of advanced rectal cancer(pT3N0M0, pStage Ⅱa). For ascending colon polyps, endoscopic submucosal dissection was performed with a diagnosis of adenocarcinoma in adenoma(pTisN0M0, pStage 0)in September 2007. In June 2016, laparoscopic ileocecal resection was performed with a diagnosis of advanced cecum cancer(pT3N0M0, pStage Ⅱa). Follow up CT images showed a liver tumor in S4. Partial liver resection was performed in October 2010. Postoperative pathological diagnosis was hepatocellular carcinoma(pT2N0M0, pStage Ⅱ). Prostate cancer(cT2aN0M0)was treated by androgen deprivation therapy from February 2018. Although he had high‒frequency microsatellite instability, germline mutations in hMLH1 and hMSH2 genes were not detected. Histopathological examination showed that each tumor was an independent tumor and had not metastasized from any others. The patient had a good clinical course after these treatment until now.
