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Association of Dip in eGFR With Clinical Outcomes in Unilateral Primary Aldosteronism Patients After Adrenalectomy

title: Association of Dip in eGFR With Clinical Outcomes in Unilateral Primary Aldosteronism Patients After Adrenalectomy abstract: Context: Primary aldosteronism (PA) leads to kidney function deterioration after treatment, but the effects of the estimated glomerular filtration rate (eGFR) dip following adrenalectomy and its long-term implications are unclear.Objective: This study aims to examine eGFR dip in patients with unilateral PA (uPA) after adrenalectomy and clarify their long-term prognosis.Methods: This multicenter prospective population-based cohort study, enrolled patients with uPA who underwent adrenalectomy. Patients were divided into 4 groups based on their eGFR dip ratio. Outcomes investigated included mortality, cardiovascular composite events, and major adverse kidney events (MAKEs).Results Among 445 enrolled patients, those with an eGFR dip ratio worse than -30% (n = 74, 16.6%) were older, had higher blood pressure, higher aldosterone concentration, and lower serum potassium levels. During 5.0 +/- 3.6 years of follow-up, 2.9% died, 14.6% had cardiovascular composite events, and 17.3% had MAKEs. The group with eGFR dip worse than -30% had a higher risk of MAKEs (P < .001), but no significant differences in mortality (P = .295) or new-onset cardiovascular composite outcomes (P = .373) were found. Multivariate analysis revealed that patients with an eGFR dip ratio worse than -30% were significantly associated with older age (odds ratio [OR], 1.04), preoperative eGFR (OR, 1.02), hypokalemia (OR, 0.45), preoperative systolic blood pressure (OR, 1.03), and plasma aldosterone concentration (OR, 0.99).Conclusion: Within 5 years post adrenalectomy, 17.3% of patients had reduced kidney function. Notably, individuals with an eGFR dip ratio worse than -30% faced higher MAKE risks, underscoring the need to monitor kidney function in PA patients after surgery.

Artesunate Exhibits Synergy With Cisplatin and Cytotoxicity for Upper Tract and Bladder Urothelial Carcinoma Cells

title: Artesunate Exhibits Synergy With Cisplatin and Cytotoxicity for Upper Tract and Bladder Urothelial Carcinoma Cells abstract: Background/Aim: Urothelial carcinoma (UC) may arise from the urothelium of the upper tract and the bladder. Cisplatin-based therapy remains the gold standard for UC treatment. The poor 5-year survival rate of UC patients creates an urgent need to develop new drugs for advanced UC therapy. Artesunate (ART), a traditional Chinese medicine for treating malaria, is a potential anticancer agent, but its antigrowth effects on upper tract and bladder UC have not been investigated. Materials and Methods: The antigrowth effect of ART in HT 1376 (bladder UC cells) and BFTC 909 [upper tract urothelial carcinoma (UTUC) cells] was determined by the CCK-8 assay. Flow cytometric analysis was used to evaluate the cell cycle distribution and apoptosis. The cell cycle, apoptosis, and autophagy-related protein expression were analyzed by western blotting. The efficacy of combination treatment with cisplatin was determined by the Calcusyn software. Results: ART induced HT 1376 and BFTC 909 cell death in a concentration- and time-dependent manner, inducing G2/M cell-cycle arrest. ART induced apoptosis and redox imbalance in HT 1376 and BFTC 909 cells. Application of the reactive oxygen species death in ART-treated UC cells. BFTC 909 cells show a better response after ART treatment. Conclusion: ART may be a candidate drug for treating UTUC and bladder UC while increasing the therapeutic effect of cisplatin.

Effect of extra-low dose levothyroxine supplementation on pregnancy outcomes in women with subclinical hypothyroidism undergoing in vitro fertilization and embryo transfer

title: Effect of extra-low dose levothyroxine supplementation on pregnancy outcomes in women with subclinical hypothyroidism undergoing in vitro fertilization and embryo transfer abstract: Objective: This study was undertaken to test the therapeutic effect of extra-low dose of levothyroxine (LT4; 25 mcg/day) to preconception and pregnant women with subclinical hypothyroidism (SCH). Materials and methods: This is a retrospective study, SCH women who succeeded in their first in vitro fertilization (IVF) cycle between January 1, 2018, to December 31, 2020 were included. SCH is defined as normal serum free thyroxine (T4) level and an elevated serum thyroid stimulating hormone (TSH) level >4 mIU/L. Extra-low dose of levothyroxine (LT4; 25 mcg/day) was prescribed to the SCH women from the establish of diagnosis of SCH to the end of pregnancy. The pregnancy outcomes (miscarriage, live birth, preterm birth, and small for gestational age baby) were compared to the euthyroid pregnant women. Results: Totally, 589 women were screened, and 317 cases received their first time IVF treatment. 167 women were clinically pregnant after IVF treatment, 155 of them were euthyroid and 12 of these women were diagnosed to have SCH. The average age of the participants was 35 years old. There were no significant differences in age, body mass index (BMI), anti-mullerian hormone (AMH), types of embryo transfer, number of embryos to transfer, or embryo stage during transfer between two groups. The live birth rate, miscarriage rate, and preterm birth rate in women with SCH supplemented with extra-low dose of LT4 were non-inferior to euthyroid patients (miscarriage rate: P = 0.7112; live birth rate: P = 0.7028; preterm delivery: P = 0.2419; small for gestational age: P = 0.2419). Conclusion: Our result demonstrated that supplementation with extra-low dose of levothyroxine at 25 mcg/day to SCH women can produce the comparable obstetrical and neonatal outcome as that in euthyroid pregnant women. Accordingly, we suggest extra-low-dose of levothyroxine may be considered as a safe and effective alternative for those SCH pregnant women who were not tolerated to the standard dose of levothyroxine.(c) 2023 Taiwan Association of Obstetrics & Gynecology. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Proper phosphorylation of septin 12 regulates septin 4 and soluble adenylyl cyclase expression to induce sperm capacitation

title: Proper phosphorylation of septin 12 regulates septin 4 and soluble adenylyl cyclase expression to induce sperm capacitation abstract: Septin-based ring complexes maintain the sperm annulus. Defective annular structures are observed in the sperm of Sept12- and Sept4-null mice. In addition, sperm capacitation, a process required for proper fertilization, is inhibited in Sept4-null mice, implying that the sperm annulus might play a role in controlling sperm capacitation. Hence, we analyzed sperm capacitation of sperm obtained from SEPT12 Ser196 phosphomimetic (S196E), phosphorylation-deficient (S196A), and SEPT4-depleted mutant mice. Capacitation was reduced in the sperm of both the Sept12 S196E- and Sept12 S196A-knock-in mice. The protein levels of septins, namely, SEPT4 and SEPT12, were upregulated, and these proteins were concentrated in the sperm annulus during capacitation. Importantly, the expression of soluble adenylyl cyclase (sAC), a key enzyme that initiates capacitation, was upregulated, and sAC was recruited to the sperm annulus following capacitation stimulation. We further found that SEPT12, SEPT4, and sAC formed a complex and colocalized to the sperm annulus. Additionally, sAC expression was reduced and disappeared in the annulus of the SEPT12 S196E- and S196A-mutant mouse sperm. In the sperm of the SEPT4-knockout mice, sAC did not localize to the annulus. Thus, our data demonstrate that SEPT12 phosphorylation status and SEPT4 activity jointly regulate sAC protein levels and annular localization to induce sperm capacitation.