Albuminuria is a measurement and determinant factor for diabetic kidney disease (DKD). Angiotensin receptor blocker (ARB) is recommended for albuminuria in DKD with variable response. To find surrogate markers to predict the therapeutic effect of ARB, we carried out a prospective study to correlate plasma metabolites and the progression of renal function/albuminuria in DKD patients. A total of 56 type 2 diabetic patients with various stages of chronic kidney disease and albuminuria were recruited. ARB was prescribed once albuminuria was established. Urinary albumin-to-creatinine ratio (UACR) was determined before and six months after ARB treatment, with a ≥30% reduction of UACR considered an ARB responder. Plasma levels of 145 metabolites were measured before ARB treatment; only those associated with albuminuria were selected and compared between ARB responders and non-responders. Both lower tryptophan (Trp ≤ 46.75 μmol/L) levels and a higher kynurenine/tryptophan ratio (KTR ≥ 68.5 × 10⁻³) were significantly associated with macroalbuminuria (MAU), but only KTR (≥54.7 × 10⁻³) predicts ARB responsiveness (sensitivity 90.0%, specificity 50%) in MAU. Together, these data suggest that the kynurenine/tryptophan ratio predicts angiotensin receptor blocker responsiveness in patients with diabetic kidney disease.

Differentiated thyroid cancer (DTC) patients are usually known for their excellent prognoses. However, some patients with DTC develop refractory disease and require novel therapies with different therapeutic mechanisms. Targeting Wee1 with adavosertib has emerged as a novel strategy for cancer therapy. We determined the effects of adavosertib in four DTC cell lines. Adavosertib induces cell growth inhibition in a dose-dependent fashion. Cell cycle analyses revealed that cells were accumulated in the G2/M phase and apoptosis was induced by adavosertib in the four DTC tumor cell lines. The sensitivity of adavosertib correlated with baseline Wee1 expression. In vivo studies showed that adavosertib significantly inhibited the xenograft growth of papillary and follicular thyroid cancer tumor models. Adavosertib therapy, combined with dabrafenib and trametinib, had strong synergism in vitro, and revealed robust tumor growth suppression in vivo in a xenograft model of papillary thyroid cancer harboring mutant BRAF^V600E, without appreciable toxicity. Furthermore, combination of adavosertib with lenvatinib was more effective than either agent alone in a xenograft model of follicular thyroid cancer. These results show that adavosertib has the potential in treating DTC.

Background: Renin-angiotensin system inhibitors (RASi), comprising angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB) are known for cardio- and renoprotection. However, there is uncertainty regarding the continuation of ACEi or ARB treatment in patients with chronic kidney disease (CKD) stages 3–5.Methods: In this meta-analysis, we systematically searched all relevant studies published in PubMed, Embase, and the Cochrane Library up to 30 May 2024. Our objective was to assess the impacts of continuation or discontinuation of RASi in patients with CKD stages 3–5 on all-cause mortality, end-stage kidney disease, major adverse cardiovascular events (MACE), and hyperkalemia. We rated the certainty of the evidence using the Cochrane methods and the GRADE approach.Results: The search identified 520 studies, of which 8 studies, encompassing a total of 243,775 patients, were included in the analysis. The incidence of all-cause mortality was 40.3% (29,993 out of 74,447 patients), while ESKD occurred in 27.9% (8,992 out of 32,191 patients), MACE in 37.3% (11,225 out of 30,059 patients), and hyperkalemia in 39.4% (8,533 out of 21,642 patients). Pooled analysis revealed that patients who discontinued RASi therapy had a higher risk of developing ESKD compared to those who continued treatment [Hazard ratio (HR): 1.40, 95% confidence interval (CI): 1.19–1.65, P < 0.001], but a lower risk of hyperkalemia [Odds ratio (OR): 0.68, 95% CI: 0.60–0.77, P < 0.001]. There were no significant differences between the groups in all-cause mortality (HR: 1.34, 95% CI: 0.91–1.95, P = 0.135) and MACE (OR: 1.27, 95% CI: 0.93–1.73, P = 0.138).Conclusion: Patients who discontinued RASi therapy exhibited a higher risk of developing ESKD but a reduced risk of hyperkalemia compared to those who continued RASi treatment. However, there were no significant differences in all-cause mortality and MACE between the two groups.Systematic Review Registration: identifer, PROSPERO (CRD42023494698).

The incidence of thyroid cancer has increased substantially worldwide. However, the overall mortality risk and actual causes of death in thyroid cancer patients have not been extensively evaluated. In this study, patients with thyroid cancer diagnosed between 2001 and 2017 were analyzed from Taiwan’s National Health Insurance Research Database. We compared these patients with control subjects matched for age, gender, history of cardiovascular disease (CVD), hyperlipidemia, diabetes mellitus, hypertension, and occupation to assess the risk of overall mortality and cause-specific mortality. Finally, our cohort comprised 30,778 patients with thyroid cancer. Three hundred and ninety-eight deaths (1.29%) occurred during a median follow-up of 60.0 months (range: 30.3 to 117.6 months). The primary cause of death was thyroid cancer mortality (31.2%), followed by other malignancy-related mortality (29.9%) and CVD mortality (12.3%). The overall mortality risk was similar between the thyroid cancer and control groups (unadjusted hazard ratio (HR): 0.98; 95% confidence interval (CI): 0.88–1.10); the adjusted HR was 1.07 (95% CI: 0.95–1.20) after multivariate adjustment for age, gender, history of CVD, hyperlipidemia, diabetes mellitus, hypertension, and occupation. The risk of other malignancy-related mortality was comparable between two groups. CVD mortality risk was lower in the thyroid cancer group, with an unadjusted HR of 0.51 (95% CI: 0.38–0.69) and adjusted HR of 0.56 (95% CI: 0.42–0.76). In conclusion, patients with thyroid cancer had excellent overall survival. Thyroid cancer-specific mortality was the leading cause of death, highlighting the importance of thyroid cancer management. Thyroid cancer patients had lower CVD mortality risk than the general population.

Anti-hypertensive medications may affect plasma renin activity and/or plasma aldosterone concentration, misleading the interpretation of the aldosterone-to-renin ratio when screening for primary aldosteronism. The Task Force of Taiwan PA recommends that, when necessary, using α-adrenergic receptor blocking agents, centrally acting α-adrenergic agonists, and/or non-dihydropyridine calcium channel blockers should be considered to control blood pressure before screening for PA. We recommend temporarily holding β-adrenergic receptor blocking agents, mineralocorticoid receptor antagonists, dihydropyridine calcium channel blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and all diuretics before screening for PA. Further large-scale randomized controlled studies are required to confirm the recommendations.