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Background: The guidelines recommend the initiation or up-titration of heart failure (HF) treatments following an HF hospitalization; however, concerns about adverse events may limit the use of mineralocorticoid receptor antagonists (MRAs). Patient profiles or disease severity might impact adverse events associated with MRA therapy in acute HF., Methods: The EARLIER trial included patients with acute HF who were randomized to eplerenone or placebo over 6 months. Adverse events (i.e., worsening renal function [WRF], hyperkalemia, hypotension, and volume depletion/dehydration) were assessed. HF-related outcome included a composite of all-cause mortality, HF re-hospitalization, investigator-reported worsening HF and out-of-hospital diuretic intensification., Results: In 297 patients (mean age: 67 ± 13 years; 73% males), adverse events were observed: 44.4% experienced WRF (>20% drop in estimated glomerular filtration rate[eGFR] and/or investigator-reported WRF), 8.4% had hyperkalemia (potassium >5.5 mmol/L and/or investigator-reported hyperkalemia), 27.9% experienced hypotension (systolic blood pressure[SBP] <90 mmHg and/or investigator-reported hypotension), and 16.8% had investigator-reported volume depletion/dehydration. Eplerenone vs. placebo did not elevate the incidence of these events (all-p-values>0.0 5). Multivariable analyses revealed that, irrespective of treatment allocation, older age (>7 5 years), prevalent diabetes, symptomatic congestion, and microalbuminuria were associated with increased risk of WRF. Baseline eGFR<60 ml/min/1.73m 2 and SBP < 90 mmHg predicted hyperkalemia and hypotension, respectively, while older patients were more likely to experience volume depletion/dehydration. However, these patient profiles did not alter the benefit of eplerenone on outcomes (HR [9 5%CI] = 0.53 [0.29 to 0.97], P = 0.04; all-p-for-interaction>0.10)., Conclusion: Eplerenone did not increase adverse events compared with placebo in acute HF. Importantly, disease severity and comorbidity burden greatly influence adverse events, but not benefit from eplerenone., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Acne vulgaris is a common skin disease that greatly impacts the quality of life of affected individuals. Several treatment modalities are available for acne, with variable degrees of success. Our aim was to compare the safety and efficacy of topical spironolactone 5% gel and topical dapsone 5% gel as treatment modalities for acne vulgaris. The study included 28 patients with mild to moderate acne. They were randomly divided into two equal groups. Group I treated with topical spironolactone 5% gel, and group II treated with topical dapsone 5% gel. In both groups, the gel was applied twice daily for 12 weeks, and patients were evaluated using the acne severity index. Group I included 14 patients [11 (78.6%) females and 3 (21.4%) males]. More than one-half of this group (64.3%) had moderate acne severity. Group II included 14 patients [12 (85.7%) females and 2 (14.3%) males]. Half of patients had moderate acne severity. Therapeutic response was poor, moderate, good, and excellent (14.3%), (28.6%), (50%), (7.1%), respectively, in topical spironolactone group versus poor, moderate, and good (50%), (42.9%), (7.1%), respectively, in topical dapsone group. The therapeutic response between the studied groups was statistically significant in favor of the topical spironolactone group. Regarding adverse effects, burning sensation was evident after application of topical spironolactone while itching was significantly common with topical dapsone. The data provided by the current study support the use of topical spironolactone 5% gel in treating acne vulgaris in both male and female patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Spironolactone (SPL) is an effective treatment for women acne, but other effects on skin biophysical properties remain to be investigated., Objectives: The aim of the current study was to explore the effects of oral SPL used to treat women acne on skin biophysical properties, including hydration, transepidermal water loss (TEWL), skin surface lipid (SSL) levels, mechanical properties, color, pH, and pore size., Materials and Methods: Twenty-five Thai women with acne treated with oral SPL were followed for 6 months. Skin hydration, TEWL, SSL levels, mechanical properties, color, pH, and pore size of the forehead, chest, and inner arm were evaluated at baseline and 2, 4, and 6 months after treatment with oral SPL. Facial and upper back pore size were also assessed. Clinical outcomes were changes in these skin biophysical properties at each visit compared with baseline., Results: Skin hydration, TEWL, SSL levels, color, pH, and pore size remained stable throughout the study. Facial skin parameters at 6 months demonstrated the following changes: hydration levels, 7.60 (95% confidence interval [CI], -59.74 to 74.94); TEWL, -2.36 (95% CI, -5.77 to 1.06); L* value, 0.51 (95% CI, -0.70 to 1.72); individual typology angle, 1.65 (95% CI -2.27 to 5.57); pH, 0.01 (95% CI -0.43 to 0.46); pore size, -0.24 (95% CI, -1.21 to 0.73); and SSL levels, 7.60 (95% CI -59.74 to 74.94). Improvement of facial mechanical properties was observed. R0 (indicating skin tightness) and R1 (indicating elasticity) showed significant decreases (-0.076 [95% CI, -0.141 to -0.010] and -0.016 [95% CI, -0.033 to -0.001]). R3 and R4 (representing tiring effects) were also improved (-0.091 [95% CI, -0.158 to -0.025] and -0.022 [95% CI, -0.044 to -0.001]). Parameters in the truncal and inner arm areas remained stable, except for skin elasticity and tiring effects, which exhibited a similar trend of improvement as the facial area. The changes were notable as early as 4 months., Conclusion: Oral SPL used for acne did not impair the skin barrier. Moreover, the skin mechanical properties were improved at 4 to 6 months., (© 2024 Japanese Dermatological Association.)

Background: Mineralocorticoid receptor antagonists (MRAs) improve outcomes in patients with heart failure and reduced ejection fraction (HFrEF). However, MRAs are often underused because of hyperkalemia concerns., Objectives: The purpose of this study was to assess whether sodium zirconium cyclosilicate (SZC), a nonabsorbed crystal that traps and rapidly lowers potassium, enables MRA use in patients with HFrEF and prevalent hyperkalemia (or at high risk)., Methods: REALIZE-K is a prospective, double-blind, placebo-controlled trial in patients with HFrEF (NYHA functional class II-IV; left ventricular ejection fraction ≤40%), optimal therapy (except MRA), and prevalent hyperkalemia (or at high risk). During the open-label run-in, all participants underwent protocol-mandated spironolactone titration (target: 50 mg daily); those with prevalent (cohort 1) or incident (cohort 2) hyperkalemia during titration started SZC. Participants achieving normokalemia while on spironolactone ≥25 mg daily were randomized to continuing SZC or matching placebo for 6 months. The primary composite endpoint was proportion of participants with optimal response (normokalemia, on spironolactone ≥25 mg daily, no rescue for hyperkalemia [months 1-6])., Results: Of 365 patients (run-in), 202 were randomized. Baseline characteristics included mean age 70 years, prevalent comorbidities (78% estimated glomerular filtration rate <60 mL/min/1.73 m 2 , 38% atrial fibrillation/flutter), high N-terminal pro B-type natriuretic peptide (median 1,136 pg/mL), and high HFrEF therapy use (64% sacubitril/valsartan, 96% beta-blocker, 42% sodium glucose co-transporter 2 inhibitor). At randomization, 78% were receiving spironolactone 50 mg daily., Conclusions: REALIZE-K is the first trial to evaluate whether SZC can enable rapid and safe MRA optimization and long-term continuation in patients with HFrEF and prevalent/high risk of hyperkalemia. (Study to Assess Efficacy and Safety of SZC for the Management of High Potassium in Patients with Symptomatic HFrEF Receiving Spironolactone [REALIZE-K]; NCT04676646)., Competing Interests: Funding Support and Author Disclosures The REALIZE-K trial was funded by AstraZeneca. Drs Kosiborod, Cherney, Connelly, Desai, Guimarães, Kuthi, Lala, Madrini, Merkely, Villota, Squire, Testani, Vaclavik, Verma, Wranicz, and Petrie have received research funding in the form of grants to institutions from AstraZeneca and/or consulting for AstraZeneca. Mr Dahl, Mr Eudicone, and Ms Friberg are employees of, and hold or may hold stock in, AstraZeneca., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: To perform a comparative analysis of the efficacy of antihypertensive therapy (AHT) containing spironolactone or eplerenone in patients with essential arterial hypertension (AH) and atrial fibrillation (AF)., Material and Methods: The study included 99 male and female patients with essential AH complicated by permanent AF, who were receiving the outpatient treatment at the National Specialized Scientific and Practical Medical Center of Cardiology (Tashkent). The patients aged 61.3±9.5 years, the mean duration of AH was 12.9±8.3 years. All patients were divided into two groups: Group 1, patients who completed a 6-month combination AHT containing spironolactone (n=51); Group 2, patients who completed a 6-month combination AHT containing eplerenone (n=48). AF was diagnosed by electrocardiogram (ECG) and/or 24-hour ECG monitoring according to standard diagnostic criteria. The ECG study was performed in compliance with the American Society of Echocardiography Guidelines in M- and B-modes. The degree of structural vascular alterations was determined by the intima-media thickness of the common carotid artery by duplex scanning and microalbuminuria in morning urine. The concentrations of sex hormones were measured by the enzyme immunoassay. The serum concentrations of lipids, glucose, creatinine, and uric acid were measured by the enzymatic method. The glomerular filtration rate (GFR) was calculated with the EPI formula. Results of all studies were considered statistically significant at p&lt;0.05., Results: The proportion of patients who achieved the target diastolic blood pressure (BP) values was significantly greater in the eplerenone-containing treatment group than in the spironolactone-containing treatment group: 87.8% vs. 67.5% (p=0.043). The proportion of patients who simultaneously achieved the target systolic and diastolic BP values was slightly greater in the eplerenone-containing treatment group than in the spironolactone-containing group (100% vs. 92.1%, p=0.060). The best cardioprotective efficacy was observed in the group of combination AHT containing eplerenone. Specifically, in Group 2, the left ventricular ejection fraction (LVEF) was significantly improved compared to Group 1: from 55.4±10.6% at baseline to 52.6±9.1% in Group 1 (p&gt;0.05) and from 54.8±8.8% at baseline to 58.2±6.4% in Group 2 (p&lt;0.02). Only in Group 2, the left atrial volume index (LAVI) was significantly decreased compared to Group 1. Thus, in Group 1, the LAVI changed from 42.2±15.1 ml/m2 at baseline to 40.4±12.2 ml/m2 (p&gt;0.05) and in Group 2, from 41.2±15.3 ml/m2 at baseline to 37.3±13.5 ml/m2 after the treatment (p&lt;0.05); the ∆% LAVI in the eplerenone group was -5.9% vs. -0.36% in the spironolactone group. In men of Group 1, estradiol significantly increased from 13.9±12.6 pmol/l at baseline to 22.7±12.4 pmol/l (p&lt;0.001)., Conclusion: The good antihypertensive efficacy of the 6-month combination therapy containing eplerenone was significantly superior to spironolactone in achieving the target BP values. The eplerenone-containing treatment significantly improved LVEF and decreased LAVI compared to the spironolactone-containing treatment. A trend towards a beneficial effect of the AHT containing eplerenone on concentrations of sex hormones was noted in both women and men.

LDOM has enhanced treatment options for female AGA, yet its combined efficacy with therapies such as spironolactone, finasteride, or dutasteride remains inadequately explored. This study aims to compare the efficacy and safety of LDOM in combination with spironolactone versus LDOM with finasteride or dutasteride in women with AGA. Our analysis revealed that both combination therapies produced similar improvements in hair growth and had comparable safety profiles. Although the LDOM with finasteride/dutasteride group showed a greater average increase in hair width and density, these differences were not statistically significant. These results endorse the use of LDOM in combination with either spironolactone or finasteride/dutasteride for female AGA, and underscore the necessity for further research to validate these findings and assess long-term treatment outcomes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The combination of torsemide and spironolactone presents a promising approach to managing conditions such as edema and hypertension. Torsemide, a loop diuretic, enhances diuresis by inhibiting sodium reabsorption in the kidneys, while spironolactone, a potassium-sparing diuretic and mineralocorticoid receptor antagonist (MRA), complements this effect by preventing potassium loss and offering additional cardiovascular benefits. This review examines clinical evidence supporting their combined effectiveness in treating fluid retention and improving outcomes in conditions like heart failure (HF). Given the limited research available, it is essential to carefully evaluate patient-specific factors. However, several side effects necessitate careful patient selection and monitoring. Moreover, optimizing dosing regimens is crucial to ensure the safety and efficacy of torsemide and MRAs in clinical settings., (© Journal of the Association of Physicians of India 2024.)

Background: Acne is common, can cause significant impact on quality of life and is a frequent reason for long-term antibiotic use. Spironolactone has been prescribed for acne in women for many years, but robust evidence is lacking., Objective: To evaluate whether spironolactone is clinically effective and cost-effective in treating acne in women., Design: Pragmatic, parallel, double-blind, randomised superiority trial., Setting: Primary and secondary healthcare and community settings (community and social media advertising)., Participants: Women aged 18 years and older with facial acne persisting for at least 6 months, judged to potentially warrant oral antibiotic treatment., Interventions: Participants were randomised 1 : 1, using an independent web-based procedure, to either 50 mg/day spironolactone or matched placebo until week 6, increasing to 100 mg/day spironolactone or matched placebo until week 24. Participants continued usual topical treatment., Main Outcome Measures: Primary outcome was the adjusted mean difference in Acne-Specific Quality of Life symptom subscale score at 12 weeks. Secondary outcomes included Acne-Specific Quality of Life total and subscales; participant self-assessed improvement; Investigator's Global Assessment; Participant's Global Assessment; satisfaction; adverse effects and cost-effectiveness., Results: Of 1267 women assessed for eligibility, 410 were randomised (201 intervention, 209 control), 342 in the primary analysis (176 intervention, 166 control). Mean age was 29.2 years (standard deviation 7.2) and 7.9% (28/356) were from non-white backgrounds. At baseline, Investigator's Global Assessment classified acne as mild in 46%, moderate in 40% and severe in 13%. At baseline, 82.9% were using topical treatments. Over 95% of participants in both groups tolerated the treatment and increased their dose. Mean baseline Acne-Specific Quality of Life symptom subscale was 13.0 (standard deviation 4.7) across both groups. Mean scores at week 12 were 19.2 (standard deviation 6.1) for spironolactone and 17.8 (standard deviation 5.6) for placebo [difference favouring spironolactone 1.27 (95% confidence interval 0.07 to 2.46) adjusting for baseline variables]. Mean scores at week 24 were 21.2 (standard deviation 5.9) in spironolactone group and 17.4 (standard deviation 5.8) in placebo group [adjusted difference 3.77 (95% confidence interval 2.50 to 5.03) adjusted]. Secondary outcomes also favoured spironolactone at 12 weeks with greater differences at 24 weeks. Participants taking spironolactone were more likely than those taking placebo to report overall acne improvement at 12 weeks {72.2% vs. 67.9% [adjusted odds ratio 1.16 (95% confidence interval 0.70 to 1.91)]} and at 24 weeks {81.9% vs. 63.3% [adjusted odds ratio 2.72 (95% confidence interval 1.50 to 4.93)]}. Investigator's Global Assessment was judged successful at week 12 for 31/201 (18.5%) taking spironolactone and 9/209 (5.6%) taking placebo [adjusted odds ratio 5.18 (95% confidence interval 2.18 to 12.28)]. Satisfaction with treatment improved in 70.6% of participants taking spironolactone compared with 43.1% taking placebo [adjusted odds ratio 3.12 (95% confidence interval 1.80 to 5.41)]. Adverse reactions were similar between groups, but headaches were reported more commonly on spironolactone (20.4% vs. 12.0%). No serious adverse reactions were reported. Taking account for missing data through multiple imputation gave an incremental cost per quality-adjusted life-year of £27,879 (adjusted) compared to placebo or £2683 per quality-adjusted life-year compared to oral antibiotics., Conclusions: Spironolactone resulted in better participant-reported and investigator-reported outcomes than placebo, with greater differences at week 24 than week 12., Trial Registration: This trial is registered as ISRCTN12892056 and EudraCT (2018-003630-33)., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/13/02) and is published in full in Health Technology Assessment ; Vol. 28, No. 56. See the NIHR Funding and Awards website for further award information.

Background: Patients experiencing myocardial infarction (MI) remain at high risk of future major adverse cardiovascular events (MACE). While low-dose colchicine and spironolactone have been shown to decrease post-MI MACE, more data are required to confirm their safety and efficacy in an unselected post-MI population. Therefore, we initiated the CLEAR SYNERGY (OASIS 9) trial to address these uncertainties., Methods: The CLEAR SYNERGY trial is a 2 × 2 factorial randomized controlled trial of low-dose colchicine 0.5 mg daily versus placebo and spironolactone 25 mg daily versus placebo in 7,062 post-MI participants who were within 72 hours of the index percutaneous coronary intervention (PCI). We blinded participants, healthcare providers, research personnel, and outcome adjudicators to treatment allocation. The primary outcome for colchicine is the first occurrence of the composite of cardiovascular death, recurrent MI, stroke, or unplanned ischemia-driven revascularization. The coprimary outcomes for spironolactone are (1) the composite of the total numbers of cardiovascular death or new or worsening heart failure and (2) the first occurrence of the composite of cardiovascular death, new or worsening heart failure, recurrent MI or stroke. We finished recruitment with 7,062 participants from 104 centers in 14 countries on November 8, 2022, and plan to present the results in the fall of 2024., Conclusions: CLEAR SYNERGY is a large international randomized controlled trial that will inform the effects of low-dose colchicine and spironolactone in largely unselected post-MI patients who undergo PCI. (ClinicalTrials.gov Identifier: NCT03048825)., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the association between spironolactone use and controlled ovarian hyperstimulation (COH) outcomes., Methods: Retrospective study, including patients who underwent COH. Oocyte yield and maturation rates were compared by categories of spironolactone use at the start of their cycle., Results: 402 patients were included. 83 patients continued spironolactone, 44 patients discontinued spironolactone, and 275 matched control patients were spironolactone-naïve. No difference was observed in the number of oocytes retrieved (17 ± 14 vs. 15 ± 13, p = 0.4) or mature oocytes vitrified (15 ± 9.5 vs. 12 ± 11, p = 0.4) in patients who continued spironolactone use and spironolactone naïve patients, respectively. When comparing patients who continued spironolactone use and patients who discontinued spironolactone use, no difference was seen in the number of oocytes retrieved (17 ± 14 vs. 17.5 ± 7.8, p = 0.9) or mature oocytes vitrified (15 ± 9.5 vs. 13.5 ± 6.5, p = 0.5), respectively. There was no observed relationship between total daily spironolactone dose (< 100mg/day, 100mg/day, 150mg/day and > 200 mg/day) and the total number of mature oocytes vitrified (respectively, 14.0 ± 13.0, 16.0 ± 7.8, 14.0 ± 4.5, 11.0 ± 7.0 oocytes, p = 0.4)., Conclusions: This is the first study to evaluate the association between spironolactone and oocyte yield and maturation rates during COH cycles. These findings can assist in counseling patients on the implications of continuing spironolactone during COH cycle., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To compare the efficacy and safety of subthreshold micropulse laser (SML) and spironolactone therapy for treating chronic central serous chorioretinopathy (CSC)., Methods: This was a quasi-randomized controlled trial. Eligible patients were quasi-randomized at a 1:1 ratio to receive SML or oral spironolactone and were assessed at 3 months after treatment., Results: A total of 84 patients (90 eyes) were randomly assigned to receive SML (n = 45) or spironolactone (n = 39) initially. At last follow-up, 59.5% of patients in the SML group had complete resolution of subretinal fluid (SRF) compared to 43.6% in spironolactone group (P = 0.362). The mean visual acuity did not significantly improve between the two groups (0.38 ± 0.44 vs. 0.43 ± 0.43 logMAR). The central retinal thickness was decreased from 335.06 ± 120.25 µm to 222.15 ± 94.90 µm in the SML group and from 308.02 ± 90.69 µm to 257.27 ± 102.28 µm in the spironolactone group. After treatment, subfoveal choroidal thickness, total choroidal area, and stromal and luminal choroidal area were significantly lower in the spironolactone group as compared to the SML group. During the entire visit, the recurrence rate of SRF was 9.1% in the SML group compared to 35.3% in the spironolactone group. Slight adverse events occurred more frequently in the spironolactone group (0% vs. 16%)., Conclusions: Both SML and oral spironolactone were effective and safe treatments to ameliorate retinal anatomical structures for chronic CSC. A lower recurrence rate and fewer adverse effects were observed in the SML group, and better choroidal structure recovery was seen in the spironolactone group., Translational Relevance: The investigation of SML and oral spironolactone may inform evidence-based clinical decisions for chronic CSC patients.

Acne vulgaris is prevalent among adolescents and adults worldwide and can significantly impact patients' quality of life. Steroidal molecules, including oral and intralesional corticosteroids, combined oral contraceptives (COCs), oral spironolactone, and topical clascoterone, are an important part of the acne treatment armamentarium. The recommended use, mechanism of action, and available evidence supporting the use of steroids for acne treatment are reviewed, and differences in acne clinical presentation and treatment approaches based on patient characteristics relevant to the selection of an appropriate steroid are also discussed.&nbsp;Steroid-based approaches target the systemic or local hormones (ie, testosterone and androgens) and inflammation that contribute to acne pathogenesis. Oral corticosteroids are primarily used as a short-term adjunctive therapy early in treatment, whereas intralesional corticosteroid injections are used for individual acne lesions. COCs and oral spironolactone are limited to female patients who wish to avoid pregnancy. Topical clascoterone can be used by female and male patients 12 years of age and older. Patients' characteristics (including age and patients with darker skin color) and preferences for the route of administration can impact treatment response and adherence, respectively. Overall, healthcare providers must be aware of the differences among steroidal acne treatments and use shared decision-making to select the optimal therapy. J Drugs Dermatol. 2024;23(6):404-409.&nbsp; &nbsp;&nbsp; doi:10.36849/JDD.7846.

Background: Cuff blood pressure (BP) is recommended for guiding hypertension management. However, central BP has been proposed as a superior clinical measurement. This study aimed to determine whether controlling hypertension as measured by central BP was beneficial in reducing left ventricular mass index beyond control of standard cuff hypertension., Methods: This multicenter, open-label, blinded-end point trial was conducted in individuals treated for uncomplicated hypertension with controlled cuff BP (<140/90 mm Hg) but elevated central BP (≥0.5 SD above age- and sex-specific normal values). Participants were randomized to 24-months intervention with spironolactone 25 mg/day (n=148) or usual care control (n=153). The primary outcome was change in left ventricular mass index measured by cardiac MRI. Cuff and central BPs were measured by clinic, 7-day home and 24-hour ambulatory BPs., Results: At 24-months, there was a greater reduction in left ventricular mass index (-3.2 [95% CI, -5.0 to -1.3] g/m 2 ; P =0.001) with intervention compared with control. Cuff and central BPs were lowered by a similar magnitude across all BP measurement modes (eg, clinic cuff systolic BP, -6.16 [-9.60 to -2.72] mm Hg and clinic central systolic BP, -4.96 [-8.06 to -1.86] mm Hg; P ≥0.48 all). Secondary analyses found that changes in left ventricular mass index correlated to changes in BP, with the magnitude of effect nearly identical for BP measured by cuff (eg, 24-hour systolic BP, β, 0.17 [0.02-0.31] g/m 2 ) or centrally (24-hour systolic BP, β, 0.16 [0.01-0.32] g/m 2 )., Conclusions: Among individuals with central hypertension, spironolactone had beneficial effects in reducing LV mass. Secondary analyses showed that changes in LV mass were equally well associated with lower measured standard cuff BP and central BP., Registration: URL: https://www.anzctr.org.au/; Unique identifier: ACTRN12613000053729., Competing Interests: Disclosures J.E. Sharman is principal investigator of a National Health and Medical Research Council of Australia partnership grant (S0026615) that includes a medical technology company that manufactures a central blood pressure (BP) device, not referred to in this article. He has no personal financial conflicts relating to BP technology. S. Stewart is supported by a National Health and Medical Research Council of Australia Fellowship (GNT 1135894). The other authors report no conflicts.

Objectives: This study aimed to evaluate the effectiveness of topical clascoterone (TC) compared to oral spironolactone for acne vulgaris treatment., Methods: A computerized search through PubMed/MEDLINE, SCOPUS, and the Cochrane Library was conducted to find relevant papers. We used the "netmeta" and "meta" packages for network meta-analysis (NMA) in RStudio 1.2.5019 (2009-2019 RStudio, Inc.) to conduct all of our statistical tests., Results: Seven articles (n = 2,006 patients) were included. The fixed-effect size showed that TC 1% bis in die (BID) showed potential effectiveness in reducing the inflammatory and non-inflammatory lesion count compared to placebo (Standardized mean difference, SMD = -0.27, 95% CI: -0.36 to -0.17) and (SMD = -0.31, 95% CI: -0.41 to -0.22), respectively. The random-effect size showed that TC 1% BID was significantly associated with a 12-week treatment success compared to placebo (Odds ratio, OR = 2.44, 95% CI: 1.12 to 5.30). Spironolactone 200 mg was associated with a significant reduction in total lesion count (SMD = -4.46, 95% CI: -5.60 to -3.32)., Conclusion: TC appears to reduce both inflammatory and non-inflammatory lesion count and may lead to treatment success. Spironolactone at 200 mg showed potential effectiveness in terms of total lesion count reduction. These results suggest that both TC and Spironolactone could be beneficial in treating patients with acne vulgaris., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Basendwh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Acne vulgaris commonly affects adults, adolescents, and preadolescents aged 9 years or older., Objective: The objective of this study was to provide evidence-based recommendations for the management of acne., Methods: A work group conducted a systematic review and applied the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of evidence and formulating and grading recommendations., Results: This guideline presents 18 evidence-based recommendations and 5 good practice statements. Strong recommendations are made for benzoyl peroxide, topical retinoids, topical antibiotics, and oral doxycycline. Oral isotretinoin is strongly recommended for acne that is severe, causing psychosocial burden or scarring, or failing standard oral or topical therapy. Conditional recommendations are made for topical clascoterone, salicylic acid, and azelaic acid, as well as for oral minocycline, sarecycline, combined oral contraceptive pills, and spironolactone. Combining topical therapies with multiple mechanisms of action, limiting systemic antibiotic use, combining systemic antibiotics with topical therapies, and adding intralesional corticosteroid injections for larger acne lesions are recommended as good practice statements., Limitations: Analysis is based on the best available evidence at the time of the systematic review., Conclusions: These guidelines provide evidence-based recommendations for the management of acne vulgaris., Competing Interests: Conflicts of interest Rachel V.S. Reynolds, MD, Carol E. Cheng, MD, Kelly Druby, Megha M. Tollefson, MD, and Jung Min Han, PharmD, MS, have no relationships to disclose. Howa Yeung, MD, MS, serves as an investigator for American Acne & Rosacea Society, Department of Veterans Affairs, and National Institutes of Health receiving grants and research funding; as an independent contractor for American Academy of Dermatology and Journal of the American Medical Association receiving fees; as a speaker/faculty educator for Dermatology Digest receiving honoraria. Fran Cook-Bolden, MD, serves as an advisory board member for AbbVie, Dermavant Sciences, Inc., Galderma Global, Novartis, Ortho Dermatologics, and Pfizer Inc. receiving honoraria; as an investigator for Arcutis Biotherapeutics receiving grant and research funding; as a speaker for Galderma Laboratories, LP, Journey Medical Corporation, and Ortho Dermatologics receiving honoraria; as others for Topix Pharmaceuticals, Inc. receiving other financial benefit. Seemal R. Desai, MD, serves an advisory board member for Foundation for Research & Education of Dermatology receiving fees; as a consultant for AbbVie, Allergan, Inc, Almirall, Amgen, Apogee, Avita, Ballature Beauty, Beiersdorf, Inc., Bristol-Myers Squibb, Candela Corporation, Cassiopea S.p.A., Castle Biosciences, Cutera, Inc., Dermavant Sciences, Dermira, Eli Lilly and Company, EPI Health, Ferndale Laboratories, Inc., Foamix, Galderma Laboratories, LP, Gore Range Capital, Hyphens Pharma, Incyte Corporation, Janssen Pharmaceuticals, Inc, Johnson and Johnson, Leo Pharma Inc., L'Oreal USA Inc., Lyceum Health, Ortho Dermatologics, Pfizer Inc., Revision Skincare, Sanofi/Regeneron, Scientis, Skin Science Advisors, UCB, Verrica Pharmaceuticals Inc., and VYNE Therapeutics receiving fees, honoraria, and/or stock options; as an investigator for AOBiome, LLC, Atacama Therapeutics, Dermavant Sciences, Incyte Corporation, and SkinMedica, Inc. receiving grants and research funding; as a speaker for AbbVie, Dermira, Galderma Laboratories, LP., and Pfizer Inc. receiving fees; as a stockholder for Gore Range Capital; as other role for Medscape receiving fees. Esther E. Freeman, MD, PhD, serves as an investigator for International League of Dermatologic Societies and National Institutes of Health receiving grants and research funding; as an author for UptoDate, Inc. and British Journal of Dermatology, receiving honoraria or salary; as a speaker for Harvard University. Jonette E. Keri, MD, PhD, serves as an advisory board member for Ortho Dermatologics receiving honoraria; as a consultant for Almirall receiving fees; as an investigator for Galderma USA receiving grants and research funding; as a speaker for Foamix Pharmaceuticals Ltd and VYNE Therapeutics receiving honoraria. Linda F. Stein Gold, MD, serves as an advisory board member for AbbVie, Almirall, Aqua, Dermavant Sciences, Foamix, Galderma Laboratories, L.P., GlaxoSmithKline, Incyte Corporation, La Roche-Posay Laboratorie Pharmaceutique, LEO Pharma, US, Lilly ICOS LLC, Merz Pharmaceuticals, LLC, Pfizer Inc., Promius Pharmaceuticals, Sanofi/Regeneron, Taro Pharm, and Valeant Pharmaceuticals International receiving honoraria; as a consultant for AnaptysBio, BMS, Botanix Pharmaceuticals, Cutera, Inc., Incyte Corporation, Janssen Scientific Affairs, LLC, Sol-Gel Technologies, Taro Pharm, The Acne Store, and UCB receiving honoraria or grants and research funding; as an investigator for AbbVie, Allergan, Inc., AnaptysBio, Galderma Laboratories, L.P., Leo Pharma Inc., Novartis Pharmaceuticals Corp., Pfizer Inc., Topica, and Valeant Pharmaceuticals International receiving grants and research funding; as a speaker for Actavis, Almirall, BMS, Dermira, Pfizer Inc., Sanofi/Regeneron, Sun Pharmaceutical Industries Ltd., and VYNE Therapeutics receiving honoraria. Jerry K. L. Tan, MD, serves as an advisory board member for Abbott Laboratories, Cutera, Inc., Galderma Laboratories, L.P, and Sun Pharmaceutical Industries Ltd receiving honoraria or grants and research funding; as a consultant for Bausch Health, Boots, Galderma Research & Development, LLC, and Loreal Research and Innovation receiving honoraria; as an independent contractor for Norvatis receiving fees; as an investigator for Allergan, AnaptysBio, Cutera, Inc., Eli Lilly and Co., Galderma Laboratories, L.P, Lilly ICOS LLC, Pfizer, and UCB for receiving grants and research funding; as a speaker for Bausch Health, LEO Laboratories Ltd (LEO Pharma), and Vichy Laboratories receiving honoraria. Jonathan S. Weiss, MD, serves as an advisory board member for Bristol-Myers Squibb, Dermavant Sciences, Foamix, Galderma Laboratories, L.P., Incyte Corporation, Novartis, and UCB receiving honoraria; as a consultant for Arcutis, Inc., Biofrontera, Cutera, Inc., Leo Pharma Inc, Ortho Dermatologics, and UCB receiving fees or honoraria; as an investigator for AbbVie, Bausch Health, Biofrontera, Bristol-Myers Squibb, Cutera, Inc., Dermavant Sciences, Foamix, Galderma Laboratories, L.P., LEO Pharma, Mindera, Moberg Pharma North, America LLC, Novartis, Palvella Therapeutics, and Verrica Pharmaceuticals Inc receiving grants and research funding; as a speaker for AbbVie, Arcutis, Inc., Galderma Laboratories, L.P., Ortho Dermatologics, Regeneron, and Sanofi Genzyme receiving honoraria. Peggy A. Wu, MD, serves as others for UptoDate, Inc. receiving honoraria. Andrea L. Zaenglein, MD, serves as a consultant for Church & Dwight Co., Inc. and UCB receiving fees or honoraria; as an investigator for AbbVie, Arcutis Biotherapeutics, Biofrontera AG, Galderma Laboratories, L.P., and Incyte Corporation receiving grants and research funding. John S. Barbieri, MD, MBA serves as investigator for National Institutes of Health and National Psoriasis Foundation receiving grants and research funding., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: Cyclosporin has been used for the treatment of pediatric refractory nephrotic syndrome (PRNS). However, the narrow therapeutic window and large pharmacokinetic variability make it difficult to individualize cyclosporin administration. Meanwhile, spironolactone has been reported to affect cyclosporin metabolism in PRNS patients. This study aims to explore the initial dosage optimization of cyclosporin in PRNS based on the impact of spironolactone co-administration., Methods: Monte Carlo simulation based on a previously established cyclosporin population pharmacokinetic model for PRNS was used to design cyclosporin dosing regimen., Results: In this study, the probability of drug concentration reaching the target and the convenience of times of administration were considered comprehensively. The optimal administration regimen in PRNS without spironolactone was 6, 5, 4 and 3 mg/kg cyclosporin split into two doses for the body weight of 5-8, 8-18, 18-46 and 46-70 kg, respectively. The optimal administration regimen in PRNS with spironolactone was 4, 3, 2 mg/kg cyclosporin split into two doses for body weight of 5-14, 14-65, and 65-70 kg, respectively., Conclusion: The cyclosporin dosing regimen for PRNS based on Monte Carlo simulation was systematically developed and the initial dosage optimization of cyclosporin in PRNS was recommended for the first time., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aim: The main treatment strategy in type 1 cardiorenal syndrome (CRS1) is vascular decongestion. It is probable that sequential blockage of the renal tubule with combined diuretics (CD) will obtain similar benefits compared with stepped-dose furosemide (SF)., Methods: In a pilot double-blind randomized controlled trial of CRS1 patients were allocated in a 1:1 fashion to SF or CD. The SF group received a continuous infusion of furosemide 100 mg during the first day, with daily incremental doses to 200 mg, 300 mg and 400 mg. The CD group received a combination of diuretics, including 4 consecutive days of oral chlorthalidone 50 mg, spironolactone 50 mg and infusion of furosemide 100 mg. The objectives were to assess renal function recovery and variables associated with vascular decongestion., Results: From July 2017 to February 2020, 80 patients were randomized, 40 to the SF and 40 to the CD group. Groups were similar at baseline and had several very high-risk features. Their mean age was 59 ± 14.5 years, there were 37 men (46.2%). The primary endpoint occurred in 20% of the SF group and 15.2% of the DC group (p = 0.49). All secondary and exploratory endpoints were similar between groups. Adverse events occurred frequently (85%) with no differences between groups (p = 0.53)., Conclusion: In patients with CRS1 and a high risk of resistance to diuretics, the use of CD compared to SF offers the same results in renal recovery, diuresis, vascular decongestion and adverse events, and it can be considered an alternative treatment. ClinicalTrials.gov with number NCT04393493 on 19/05/2020 retrospectively registered., (© 2021. The Author(s).)

Spironolactone (SP) is a potassium sparing diuretic with antiandrogenic properties. This study aimed at formulating SP into hyaluronic acid enriched cerosomes (HAECs) for topical management of hirsutism. HAECs were prepared by ethanol injection method, according to D-optimal design, after a proper in silico study. HAECs were evaluated by measuring their entrapment efficiency (EE%), particle size (PS), and polydispersity index (PDI). Optimal hyaluronic acid enriched cerosomes (OHAECs) were subjected to further in vitro and ex-vivo and in-vivo studies. The in silico study concluded better interactions between SP and phosphatidyl choline in presence of hyaluronic acid (HA) and high stability of their binding in water. The prepared HAECs had acceptable EE%, PS, and PDI values. The statistical optimization process suggested OHAEC containing 10.5 mg ceramide III and 15 mg HA, utilizing Kolliphor ® RH40. OHAEC had EE% and PS of 89.3 ± 0.3% and 261.8 ± 7.0 nm, respectively. OHAEC was stable for up to 3 months. It also showed a mixed tubular and vesicular appearance under transmission electron microscope. The ex vivo and in vivo studies concluded better skin deposition and accumulation of SP from OHAEC. The histopathological study demonstrated the safety of OHAEC for topical application. Therefore, OHAEC could be considered as effective system for topical application of SP to manage hirsutism, with prolonged action, coupled with minimized side effects.

Diabetic retinopathy remains a major cause of vision loss worldwide. Mineralocorticoid receptor (MR) pathway activation contributes to diabetic nephropathy, but its role in retinopathy is unknown. In this study, we show that MR is overexpressed in the retina of type 2 diabetic Goto-Kakizaki (GK) rats and humans and that cortisol is the MR ligand in human eyes. Lipocalin 2 and galectin 3, two biomarkers of diabetes complications regulated by MR, are increased in GK and human retina. The sustained intraocular delivery of spironolactone, a steroidal mineralocorticoid antagonist, decreased the early and late pathogenic features of retinopathy in GK rats, such as retinal inflammation, vascular leakage, and retinal edema, through the upregulation of genes encoding proteins known to intervene in vascular permeability such as Hey1 , Vldlr , Pten , Slc7a1 , Tjp1 , Dlg1 , and Sesn2 but did not decrease VEGF. Spironolactone also normalized the distribution of ion and water channels in macroglial cells. These results indicate that MR is activated in GK and human diabetic retina and that local MR antagonism could be a novel therapeutic option for diabetic retinopathy., (© 2021 by the American Diabetes Association.)

Hirsutism is a dermatological condition that refers to the excessive growth of hair in androgen-sensitive areas in women. Recently, the enhancement of the visible signs of a hairy female has taken special concern that affected the quality of life. The present study was developed to compare the follicular targeting effect of topical spironolactone (SP) or progesterone (PG)-loaded nanostructured lipid carrier (NLC) on the management of hirsutism. Four NLC formulations were prepared using cold homogenization techniques and pharmaceutically evaluated. SP-NLC and PG-NLC topical hydrogels were prepared to explore their pharmacological effect on letrozole induced polycystic ovarian syndrome (PCOS) in rats. Inflammatory mediators, antioxidant, and hormonal parameters were assayed. Additionally, histopathological examination was carried out to confirm the successful induction of PCOS. Results confirmed that all NLC formulations have a spherical shape with particle size ranged from 225.92 ± 0.41 to 447.80 ± 0.66 nm, entrapment efficiency > 75%, and zeta potential (- 31.4 to - 36.5 mV). F1 and F3 NLCs were considered as selected formulations for SP and PG, respectively. Female Wistar rats treated with F1 formulation for 3 weeks displayed better outcomes as manifested by the measured parameters as compared to the other tested groups. A significant reduction in hair follicle diameter and density was observed after topical application of SP or PG nano-gels. Finally, the outcomes pose a strong argument that the development of topically administered SP-NLC can be explored as a promising carrier over PG-NLC for more effectual improvement in the visible sign of hirsutism., (© 2021. American Association of Pharmaceutical Scientists.)

Background: Spironolactone reduces morbidity and mortality in patients with heart failure (HF) with reduced ejection fraction (EF) and decreases hospitalizations in HF with preserved EF. To minimize the risk of hyperkalemia, patients must have an estimated glomerular filtration rate (eGFR) > 30 mL/min/1.73 m 2 and potassium < 5.0 mEq/L prior to initiation; however, spironolactone is prescribed outside these parameters. The objective of this study was to evaluate the safety and tolerability of spironolactone in patients with HF and chronic kidney disease (CKD)., Methods: This single-center, retrospective cohort study evaluated patients ≥ 18 years with HF and CKD stages 3-5 who received ≥ 48 h of spironolactone therapy and were hospitalized from February 2018 to August 2019. The primary outcome was incidence of hyperkalemia (potassium ≥ 5.5 mEq/L)., Results: Overall, 121 patients were evaluated: 52.1% (n = 63) had an EF > 40% and 47.9% (n = 58) had an EF ≤ 40% with 69.4% (n = 84) CKD stage 3, 24.8% (n = 30) stage 4, and 5.8% (n = 7) stage 5. Spironolactone was initiated prior to admission (PTA) for 54.5% (n = 66) of patients, while 45.5% (n = 55) of orders were initiated during hospitalization. Eight patients (6.6%) experienced inpatient hyperkalemia-all with PTA spironolactone. Patients who experienced inpatient hyperkalemia had a numerically lower eGFR that was not statistically significant (35.40 vs. 38.22 mL/min/1.73 m 2 ; p = 0.730). Patients with CKD stage 3 (n = 4) had numerically higher rates of inpatient hyperkalemia than stages 4 (n = 1) or 5 (n = 3) (50%, 12.5%, and 37.5% respectively; p < 0.05)., Conclusion: Spironolactone may be safe to initiate in hospitalized patients with HF and CKD; however, appropriateness of therapy must be assessed upon admission to the hospital. Larger studies are needed for conclusive results.

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an important cause of sudden cardiac death in young people and athletes. To date, no treatment has proven to slow the progression of the disease. Preload reducing agents such as nitrates and diuretics have shown promising results in preventing training-induced development of ARVC in a murine model., Objective: The purpose of this study was to describe our experience with preload reducing therapy in patients with ARVC and symptomatic right ventricular (RV) dysfunction., Methods: We performed retrospective chart review of prospectively collected registry data and included 20 patients with definite ARVC who had serial echocardiographic measurements and an implantable cardioverter-defibrillator. Six of the 20 patients with RV end-diastolic area (RVEDA) above median (>25 cm 2 ) and New York Heart Association functional class II-IV symptoms were successfully treated with long-term isosorbide dinitrate 5-40 mg tid (at maximum tolerated dose) and hydrochlorothiazide-spironolactone 25-25 mg daily. The main outcomes of interest were RVEDA, RV fractional area change (FAC), and RV outflow tract measurements. Generalized estimating equations with repeated measures were used to identify the association between preload reducing agents and echocardiographic structural progression., Results: Patients who received preload reducing agents (n = 6) were older and had larger RVs with lower FAC at baseline. However, treatment with preload reducing agents was associated with less RVEDA enlargement during mean 3.3 (range 1-6.7) years of treatment in multivariate analysis (% change in RVEDA associated with treatment -7.71; 95% confidence interval -13.29 to -2.13; P = .007)., Conclusion: Preload reducing agents show promising results in slowing RV enlargement in patients with ARVC and show possible disease-modifying potential., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Pharmacological targeting aberrant activation of epidermal growth factor receptor tyrosine kinase signaling is an established approach to treating lung adenocarcinoma. Osimertinib is a tyrosine kinase approved and effective in treating lung adenocarcinomas that have one of several common activating mutations in epidermal growth factor receptor. The emergence of resistance to osimertinib after a year or two is the rule. We developed a five-drug adjuvant regimen designed to increase osimertinib's growth inhibition and thereby delay the development of resistance. Areas of Uncertainty: Although the assembled preclinical data is strong, preclinical data and the following clinical trial results can be discrepant. The safety of OPALS drugs when used individually is excellent. We have no data from humans on their tolerability when used as an ensemble. That there is no data from the individual drugs to suspect problematic interaction does not exclude the possibility., Data Sources: All relevant PubMed.org articles on the OPALS drugs and corresponding pathophysiology of lung adenocarcinoma and glioblastoma were reviewed. Therapeutic Opinion: The five drugs of OPALS are in wide use in general medicine for non-oncology indications. OPALS uses the anti-protozoal drug pyrimethamine, the antihistamine cyproheptadine, the antibiotic azithromycin, the antihistamine loratadine, and the potassium sparing diuretic spironolactone. We show how these inexpensive and generically available drugs intersect with and inhibit lung adenocarcinoma growth drive. We also review data showing that both OPALS adjuvant drugs and osimertinib have data showing they may be active in suppressing glioblastoma growth.

Background: There are limited data regarding the long-term outcomes of spironolactone use for women with acne and its effect on truncal acne., Objective: To comprehensively describe outcomes of patients treated with spironolactone in routine clinical practice, including long-term outcomes., Methods: We performed a retrospective case series of 403 adult women treated for acne with spironolactone at an academic medical center between 2008 and 2019. Rates of objective, as assessed by Comprehensive Acne Severity Scale scores, and subjective acne clearance were evaluated, as well as rates of treatment discontinuation, dosage changes, and drug survival. Logistic regression was used to assess for association between incidence of menstrual adverse effects and combined oral contraceptive use., Results: As evaluated by Comprehensive Acne Severity Scale scores, at the first follow-up, 75.5%, 84.0%, and 80.2% of patients with available data had reduction or complete clearance of acne on the face, chest, and back, respectively. The mean drug survival was 470.7 days. Menstrual adverse effects were less common among those using combined oral contraception (odds ratio, 0.23; 95% confidence interval, 0.11-0.50)., Limitations: This study was conducted at a single academic medical center., Conclusions: Spironolactone improves clinical outcomes and is well tolerated for many adult women with acne using it for an extended duration., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Importance: Although recent studies and guideline recommendations indicate that potassium level monitoring is of low usefulness for healthy young women being treated for acne with spironolactone, little is known about whether these recommendations have been implemented in clinical practice., Objective: To evaluate trends in rates of potassium level monitoring among young women treated for acne with spironolactone and clinician variability in monitoring practices., Design, Setting, and Participants: This retrospective cohort study was conducted between January 1, 2008, and June 30, 2019, using data from the Optum deidentified Clinformatics Data Mart database. Participants comprised 108 547 healthy female patients aged 12 to 45 years who were treated for acne with spironolactone., Main Outcome and Measures: The primary outcome was the proportion of women who received a test for baseline potassium level and the proportion of women whose potassium levels were monitored in the first 180 days of being treated for acne with spironolactone. For clinicians who had prescribed at least 5 courses of spironolactone, the percentage of clinicians who ordered baseline potassium testing or monitoring and the percentage of clinicians who always monitored potassium were compared between 2008 and 2015 vs between 2016 and 2018., Results: For 108 547 women included in this cohort study, the mean (SD) age at the start of treatment was 30.7 (8.6) years, and the mean (SD) course duration was 159 (218) days. Between 2008 and 2018, the percentage of women whose potassium levels were monitored within 180 days of starting spironolactone by all clinicians decreased from 41.4% to 38.5%, with a decrease from 48.9% to 41.0% among dermatologists and from 39.7% to 37.7% among internists but with an increase from 71.4% to 75.4% among advanced practice clinicians (ie, nurse practitioners and physician assistants). The proportion of dermatologists who always monitored potassium decreased from 10.6% between 2008 and 2015 to 4.2% between 2016 and 2018. There was no significant difference in the proportion of internists who always monitored potassium from 2008 to 2015 (15.8%) vs from 2016 to 2018 (17.7%)., Conclusions and Relevance: Despite increasing evidence and guidelines supporting the elimination of potassium monitoring among healthy young women treated for acne with spironolactone, the present study findings suggest that potassium monitoring remains common, with substantial variability in clinician practices. There is a need for future implementation and dissemination research to understand underlying factors for this variation and to develop strategies to address this practice gap.

Clinical records of dogs with spontaneous degenerative mitral valve disease (DMVD) with clinical signs related to congestive heart failure (CHF) recruited during routine clinical practice between 2001 and 2018 at the Cardiology Unit of the Veterinary Teaching Hospital (University of Milan) were included in this retrospective cohort study. Baseline echocardiographic data were evaluated. Median survival time (MST) was calculated. Data on therapeutic treatment, ISACHC (International Small Animal Cardiac Health Council) or ACVIM (American College of Veterinary Internal Medicine) classes were reviewed based on the inclusion period and type of endpoint (i.e. cardiac death or death for other causes). A univocal classification was needed, and the patients classified in ISACHC classes II, IIIa and IIIb, visited before 2009, were reallocated to ACVIM class C. The main goal of this data review was to retrospectively evaluate 259 clinical records of subjects belonging to ACVIM C class examined between 2001 to 2018 and 202 dogs examined between 2010 to 2018. In this way, in the second group, the bias of the reclassification was avoided. The MST (median survival time) of these subjects was 531 d (2001-2018) and 335.5 d (2010-2018), respectively. Univariate survival regression analysis for subjects included from 2010 to 2018 showed as significantly related to cardiac death (CD): left atrium to aorta ratio (LA/Ao) (HR 2.754, p=0.000), E wave (HR 2.961, p=0.000), E/A ratio (HR 1.372, p=0.000), end-diastolic (HR 1.007, p=0.000) (EDVI) and end-systolic (HR 1.012, p=0.026) (ESVI) volume indexes, allometric diastolic (HR 4.018, p=0.000) (LVIDdN) and systolic (HR 2.674, p=0.049) (LVIDsN) left ventricular internal diameters, age (HR 1.006, p=0.009) and pulmonary hypertension severity (HR=1.309, p=0.012) (PH). Multivariate analysis, adjusted for age, showed that the only variable that determined a statistically significant difference in MST was PH severity (HR 1.334, p=0.033). The type of therapeutic treatment within this class was not significant for the MST of the subjects., (Copyright© by the Polish Academy of Sciences.)

Androgens play an important role in the pathogenesis of acne. Being an anti-androgen drug with many side effects, spironolactone has recently been used in dermatology as a topical therapy for acne. Off-label drug use in dermatology is common, although those drugs are basically available as compounded formulations; the choice of a proper vehicle is often neglected in that case. Alkyl polyglucosides (APGs) are a FDA certified class of polyethylene glycol (PEG)-free surfactants produced from the renewable resources. Following the preformulation tests, two different APG emulsifiers were used in this study to stabilize emulsions as carriers for topical spironolactone. Assessment of the physical stability of emulsions per se and after incorporation of 5% of spironolactone was performed using polarization microscopy, electrical conductivity and pH measurements. The skin irritation profile and moisturizing potential was assessed in vivo on human volunteers. APG-based emulsions per se and with 5% of spironolactone showed acceptable skin irritation profiles and significant potential for skin hydration, which is important in acne treatment. Good physical stability and satisfying preliminary safety profile of all investigated samples were also obtained showing that moisturizing APG-based emulsions could be promoted as vehicles for off-label topical spironolactone.

Abstract: To explore the short-term effect of high-dose spironolactone (80 mg/d) on chronic congestive heart failure (CHF).The general clinical data of 211 patients with CHF from February 2016 to August 2019 were collected and analyzed. Patients were divided into Low-dose group (taking 40 mg/d spironolactone) and High-dose group (taking 80 mg/d spironolactone) according to the patient's previous dose of spironolactone. The changes of B-type brain natriuretic peptide (BNP), NT-pro BNP (N terminal pro B type natriuretic peptide), echocardiography, 6-minute walking test (6MWT), and comprehensive cardiac function assessment data were collected for analysis.Compared with before treatment, the blood potassium of the two groups increased significantly (P < .05), but the blood potassium did not exceed the normal range. Compared with before treatment, BNP, NT-pro BNP, LVEDD, LVEDV and NYHA grading were significantly decreased (P < .05), LVEF and 6-MWT were significantly increased (P < .05). Compared with the Low-dose group, the high-dose group BNP (117.49 ± 50.32 vs 195.76 ± 64.62, P < .05), NT-pro BNP (312.47 ± 86.28 vs 578.47 ± 76.73, P < .05), LVEDD (45.57 ± 5.69 vs 51.96 ± 5.41, P <.05), LVEDV (141.63 ± 51.14 vs 189.85 ± 62.49, P < .05) and NYHA grading (1.29 ± 0.41 vs 1.57 ± 0.49, P < .05) were significantly reduced, but, 6-MWT (386.57 ± 69.72 vs 341.73 ± 78.62, P < .05), LVEF (41.62 ± 2.76 vs 36.02 ± 2.18, P < .05) and total effective rate (92.68% vs 81.39%, P < .05) increased significantly.Compared with 40 mg spironolactone, 80 mg spironolactone can rapidly reduce BNP and NT-pro BNP concentration, enhance exercise tolerance, improve clinical signs and cardiac function classification, and has better efficacy., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Polycystic ovarian syndrome (PCOS), is a multifactorial endocrine disorder in women of reproductive age. It usually associates with metabolic disorders (MDs), which aggravates the risk of infertility, cardiometabolic events and associated comorbidities in women with PCOS. Adiponectin, a circulating protein produced by adipocytes, which has been suggested to inversely correlate with MDs. Spironolactone, a non-selective mineralocorticoid receptor (MR) antagonist, has been in wide clinical use for several decades. Herein, we investigated the effects of low dose spironolactone (LDS) and the role of adiponectin in endocrine-metabolic disturbances in experimentally-induced PCOS rats. Eighteen female Wistar rats (160-180 g) were randomly allotted into 3 groups and treated with vehicle (p.o.), letrozole (LET; 1 mg/kg) and LET + LDS (0.25 mg/kg), once daily for 21 days, respectively. The results showed that LET-treated animals had features of PCOS, characterized by elevated plasma testosterone and prolactin, increased body weight gain and ovarian weight as well as disrupted ovarian cytoarchitecture and degenerated follicles. Additionally, elevated fasting blood glucose, 1 h-postload glucose and plasma insulin, impaired glucose tolerance, insulin resistance, reduced insulin sensitivity, increased plasma and ovarian lipid profile, plasma lipid peroxidation, TNF-α, IL-6 and decreased plasma glutathione peroxidase and glutathione content were observed. These alterations were associated with decreased circulating adiponectin and were reversed when treated with LDS. The present results suggest that LDS ameliorates endocrine-metabolic disturbances and inflammation-related comorbidities associated with LET-induced PCOS by modulating circulating androgen-adiponectin status., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Chronic renin-angiotensin-aldosterone system (RAAS) activation in course of heart diseases contributes to cardiac remodeling and heart failure. Myxomatous mitral valve disease (MMVD) is characterized by different stages of severity and trend of RAAS activity during the course of the disease is still uncertain. The urinary aldosterone-to-creatinine ratio (UAldo:C) has been proven to reflect RAAS activation in dogs and might be a useful marker in monitoring therapy and disease progression, but data about this parameter need to be expanded. The objective of this study was to evaluate the UAldo:C in healthy dogs and dogs with naturally occurring MMVD, and to investigate the relationships between this parameter and clinical, echocardiographic and laboratory variables., Results: The study population consisted of 149 dogs: 49 healthy and 100 MMVD dogs (45 stage B1, 13 stage B2 and 42 stage C). Urinary aldosterone-to-creatinine ratio was not significantly different among healthy and MMVD dogs of any stages. Breed, sex and age showed a significant impact on UAldo:C. In particular, Chihuahua and Cavalier King Charles spaniel showed significantly higher UAldo:C than other breeds, as well as intact females than other genders. In stage C dogs, UAldo:C appeared to be increased by spironolactone and was positively associated with furosemide dose (P = 0.024). Aldosterone breakthrough (ABT) appeared to occur in 36% (8/22) of stage C dogs not receiving spironolactone. A significant positive association between UAldo:C and left atrium-to-aortic root ratio (LA/Ao) was found., Conclusions: Individual factors such as breed, sex and age appeared to influence UAldo:C, and therapy seemed to add further variability. In the light of these results, comparing the UAldo:C of a single patient with a population-based reference value might lead to wrong interpretations and an individual monitoring should be considered. The prevalence of ABT in the present study (36%) was in line with those previously reported. However, due to the high individual variability of UAldo:C found in the study, even this result should be re-evaluated in the setting of an individual longitudinal approach. The positive association between UAldo:C and LA/Ao supports the mutual relationship between RAAS and cardiac remodeling.

There is a need to accelerate paediatric formulation evaluation and enhance quality of early stage data in drug development to alleviate the information pinch point present between formulation development and clinical evaluation. This present work reports application of DNA microarrays as a high throughput screening tool identifying markers for prediction of bioavailability and formulation driven physiological responses. With a focus on enhancing paediatric medicine provision, an oral liquid spironolactone suspension was formulated addressing a paediatric target product profile. Caco-2 cells cultured on transwell inserts were implemented in transport assays in vitro and DNA microarrays were used to examine gene expression modulation. Wistar rats were used to derive in vivo bioavailability data. In vitro , genomic, and in vivo data sets were concurrently evaluated linking drug transport and the genomic fingerprint generated by spironolactone formulation exposure. Significant changes in gene expression are reported as a result of formulation exposure. These include genes coding for ATP-binding cassette (ABC) transporters, solute carrier (SLC) transporters, cytochrome P450 (CYP) enzymes, and carboxylesterase enzymes. Genomic findings better inform pre-clinical understanding of pharmacokinetic and pharmacodynamic responses to spironolactone and its active metabolites than current in vitro drug transport assays alone.

For women with acne, their acne often persists into adulthood, with over 50% of women reporting acne between 20&ndash;29 years of age and over 35% of women reporting acne between 30&ndash;39 years of age.1 While mild acne can usually be managed with topical medications, moderate to severe acne often requires treatment with systemic medications such as oral antibiotics, spironolactone, and isotretinoin.2 Although oral antibiotics are the most common systemic medication prescribed for women with moderate to severe acne, spironolactone may represent a safe and effective therapeutic alternative that can decrease our reliance on oral antibiotics for the treatment of acne.3&ndash;5 However, while spironolactone use is increasing, oral antibiotics are still prescribed 3 to 5 times more often than spironolactone.3.

Electrolyte abnormalities are a known trigger for ventricular arrhythmia, and patients with heart disease on diuretic therapy may be at higher risk for electrolyte depletion. Our aim was to determine the prevalence of electrolyte depletion in patients presenting to the hospital with sustained ventricular tachycardia or ventricular fibrillation (VT/VF) versus heart failure, and identify risk factors for electrolyte depletion. Consecutive admissions to a tertiary care hospital for VT/VF were identified between July 2016 and October 2018 using the electronic medical record and compared with an equal number of consecutive admissions for heart failure (CHF). The study included 280 patients (140 patients in each group; mean age 63, 60% male, 59% African American). Average EF in the VT/VF and CHF groups was 30% and 33%, respectively. Hypokalemia (K < 3.5 mmol/L) and severe hypokalemia (K < 3.0 mmol/L) were present in 35.7% and 13.6%, respectively, of patients with VT/VF, compared to 12.9% and 2.7% of patients with CHF (p < 0.001 and p = 0.001, respectively, between groups). Hypomagnesemia was found in 7.8% and 5.8% of VT/VF and CHF patients, respectively (p = 0.46). Gastrointestinal illness and recent increases in diuretic dose were strongly associated with severe hypokalemia in VT/VF patients (odds ratio: 11.1 and 21.9, respectively; p < 0.001). In conclusion, hypokalemia is extremely common in patients presenting with VT/VF, much more so than in patients with CHF alone. Preceding gastrointestinal illness and increase in diuretic dose were strongly associated with severe hypokalemia in the VT/VF population, revealing a potential opportunity for early intervention and arrhythmia risk reduction., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Hyponatremia, a marker of disease severity and prognosis, has been associated with various clinical factors and drug use, especially diuretics., Methods: This observational prospective cohort study enrolled patients hospitalized at the University Hospital Center Split because of heart failure (HF). We investigated the association of clinical variables and cardiovascular drugs, including furosemide, hydrochlorothiazide, spironolactone, and their doses, with the presence of hyponatremia at admission., Results: Of the 565 included patients, 32.4% were hyponatremic, 62.6% were males, and the mean age was 73.1 ± 10.6 years. In the univariate analysis, hyponatremic patients were more often current smokers (p = 0.01), alcohol consumers (p = 0.01), receiving spironolactone (p = 0.004) or combination of furosemide and spironolactone (p = 0.003). Patients who received 50 and 100 mg of spironolactone, compared to those receiving 25 mg (p < 0.0001), as well as patients who received 250 to 500 mg of furosemide compared to ≤240 mg (p = 0.001), were significantly more often hyponatremic. In the multivariate analysis, when diuretic doses were accounted for, furosemide doses of 250 to 500 mg (p = 0.009), spironolactone doses of 50 to 100 mg (p = 0.0003), increasing age (p = 0.03), diabetes mellitus (p = 0.02) and alcohol consumption (p = 0.04) were independently associated with hyponatremia., Conclusion: High doses of furosemide and spironolactone, or concomitant use of these diuretics, seem to be an important cause of hyponatremia in HF patients, particularly in combination with advanced age, diabetes and alcohol consumption. Diuretic dose reduction may help avoid hyponatremia and improve clinical status and prognosis in such patients.

Background and Aim: The prognosis of cirrhotic patients with hepatic edema is poor. Although several short-term predictors of tolvaptan (novel diuretic agent) treatment for such patients have been reported, the factors related to long-term survival are still unclear., Methods: Among 459 patients with hepatic edema enrolled in a retrospective, multicenter collaborative study, we analyzed 407 patients who received tolvaptan., Results: Patients consisted of 266 men and 141 women, with the median age of 68 years (range, 28-93 years). The frequency of short-term responders to tolvaptan was 59.7% (243/407). In the Cox regression analysis, short-term response to tolvaptan, low average dosages of furosemide and spironolactone during tolvaptan treatment, Child-Pugh classification A and B, and absence of hepatocellular carcinoma were independent factors contributed to 1-year survival. The 1-year and long-term cumulative survival rates in short-term responders were significantly higher than those in non-responders (P = 0.011 and 0.010, respectively). Using a receiver operating characteristic curve analysis, the optimal cut-off values of average daily dosages of furosemide and spironolactone for predicting 1-year survival were 19 and 23 mg/day, respectively. The long-term cumulative survival rates in patients who received a mean dosage of spironolactone < 23 mg/day during tolvaptan treatment were significantly higher than those receiving a mean dosage of ≥ 23 mg/day (P = 0.001)., Conclusions: The present study suggests that the short-term response to tolvaptan and low dosages of conventional diuretics during tolvaptan treatment might improve the 1-year and long-term survival rates in cirrhotic patients with hepatic edema., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Purpose: To compare long-term visual/anatomical outcomes and recurrence rate between oral spironolactone (SPRL) treatment and half-dose photodynamic therapy for nonresolving central serous chorioretinopathy., Methods: This retrospective, interventional, comparative study included 50 nonresolving central serous chorioretinopathy patients who had exhibited subretinal fluid (SRF) accumulation for >3 months. Of the 50 patients, 26 (26 eyes) received oral SPRL treatment and 24 (24 eyes) received half-dose photodynamic therapy. Best-corrected visual acuity, central subfield thickness, SRF height, and subfoveal choroidal thickness were compared between groups at 1, 2, 3, 6, and 12 months after treatment by using repeated-measures analysis of variance., Results: After treatment, best-corrected visual acuity, central subfield thickness, and SRF height significantly improved in both groups, compared with baseline. There were no significant differences in best-corrected visual acuity, central subfield thickness, or SRF height between the two groups, with the exception of 3 and 12 months of follow-up for central subfield thickness (P = 0.016 and P = 0.028, respectively) and 3 months of follow-up for SRF height (P = 0.039). However, recurrence was more likely to occur in the oral SPRL group than in the half-dose photodynamic therapy group (P = 0.002)., Conclusion: Oral SPRL treatment for nonresolving central serous chorioretinopathy showed good long-term visual/anatomical outcomes, compared with half-dose photodynamic therapy. However, recurrence was more likely to occur when using oral SPRL.

An 8-year-old girl with recently diagnosed Systemic Lupus Erythematosus (SLE) (class 4 lupus nephritis with autoimmune hemolytic anemia) presented to the pediatric nephrology clinic with polyuria, tiredness and cramps; laboratory investigations revealed refractory hypokalemia, hypomagnesemia, metabolic alkalosis, hypocalciuria and hyperchloriuria. There was no history of diuretic administration. These features were consistent with the Gitelman syndrome. She required large doses of potassium and magnesium supplementation along with spironolactone, for normalization of the serum potassium and magnesium levels. Immunosuppressive therapy was continued with cyclophosphamide pulses administered on a monthly basis. The doses of potassium and magnesium supplements were tapered off over the next 6 months. The clinical exome sequencing was negative for any mutations in the SLC12A3 gene. An 'acquired' form of Gitelman syndrome has been reported earlier in association with Sjogren syndrome and systemic sclerosis. Though tubular disorders such as renal tubular acidosis have been reported in association with SLE, a Gitelman-like syndrome has not been reported earlier. This case adds Gitelman-like tubulopathy to the clinical spectrum of tubular disorders complicating SLE.

The aim of this study was to compare the efficacy and safety of adding metformin or spironolactone to rosiglitazone in women with polycystic ovary syndrome (PCOS). This is a prospective non-randomized study in a tertiary care with at in a tertiary care endocrine clinic. Women ( n  = 138) diagnosed with PCOS on the basis of Rotterdam criteria 2003 were categorized into three groups on the basis of drug intake as - rosiglitazone (R), rosiglitazone with spironolactone (R + S), and rosiglitazone with metformin (R + M). Clinical, biochemical, hormonal, and insulin sensitivity parameters were assessed at baseline and after six months of follow up. There was a significant improvement in number of menstrual cycles per year and Ferriman Gallwey (FG) score in all three groups after 6 months. Plasma insulin (0, 2 h), HOMA-IR and serum total testosterone levels decreased after six months in all the three groups. The inter group comparison showed higher efficacy of R + S in improving hyperandrogenism whereas R + M was most effective in decreasing body weight and plasma insulin levels compared to R and R + S ( p <.05). Treatment of women with PCOS using rosiglitazone alone and in combination with spironolactone or metformin is safe and efficacious with limited adverse events however randomized trials with longer duration of follow up are warranted.

Context: Polycystic ovary syndrome (PCOS) is a prevalent disorder in adolescent girls, purportedly driven by hepato-visceral fat excess, and often followed by subfertility and type 2 diabetes., Objective: We studied the baseline microRNA (miRNA) profile of girls with PCOS, and the effects of a randomized treatment with an oral contraceptive (OC) or with spironolactone-pioglitazone-metformin (SPIOMET, aiming at loss of hepato-visceral fat excess) for 1 year., Design & Patients: The miRNA profile was assessed by RNA sequencing in girls with PCOS who had participated in a randomized, open-label, single-center, pilot study (n = 31; age 15.7 years, body mass index (BMI) 23.1 kg/m2). Healthy age- and BMI-matched girls (n = 13) served as controls. Differentially expressed miRNAs were validated by RT-qPCR in the entire study population. Post-treatment ovulation rates were assessed by salivary progesterone in PCOS girls., Setting: Endocrinology Department, University Hospital., Results: Girls with PCOS, compared with controls, had markedly reduced concentrations of circulating miR-451a, miR-652-3p, miR-106b-5p, and miR-206; pathway enrichment analysis showed that these miRNAs target genes involved in energy homeostasis and cell cycle control. In the present study, miR-451a could diagnose PCOS with 100% sensitivity and 100% specificity. SPIOMET (but not OC) was accompanied by on-treatment normalization of the miRNA profile in girls with PCOS; miR-451a concentrations after 1 year on OC or SPIOMET treatment associated closely (r = 0.66; P < .0001) with post-treatment ovulation rates., Conclusion: SPIOMET treatment for 1 year normalizes the miRNA profile of girls with PCOS. Circulating miR-451a may become a biomarker to guide the diagnosis and treatment of PCOS in adolescence., (© Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

What Is Known and Objective: Hashimoto's thyroiditis, also referred to as autoimmune thyroiditis, is characterized by sexual dimorphism, suggesting an important role of sex hormones in its development. No interventional study has investigated whether drugs exerting antiandrogen properties affect thyroid antibody titres and thyroid function tests in subjects with autoimmune thyroiditis., Methods: This study included 35 levothyroxine-naïve men with euthyroid Hashimoto's thyroiditis. At the physician's discretion, 18 men were then treated with spironolactone (50-200 mg daily), while the remaining patients (n = 17) received other diuretics. Serum levels of thyrotropin, free thyroid hormones, testosterone and 25-hydroxyvitamin D, as well as titres of thyroid peroxidase and thyroglobulin, were measured at the beginning of the study and 6 months later. Based on hormone levels, constant structure parameters of thyroid homeostasis were calculated., Results and Discussion: At baseline, there was no difference between the treatment arms in terms of thyroid antibody titres, hormone levels and the calculated parameters of thyroid homeostasis. Thirty-two patients completed the study. Spironolactone increased thyroid antibody titres, decreased testosterone and 25-hydroxyvitamin D levels and reduced SPINA-GT. The drug produced a neutral effect on serum levels of thyrotropin, free thyroid hormones, Jostel's thyrotropin index and SPINA-GD. The effect of spironolactone on antibody titres correlated with treatment-induced changes in SPINA-GT, testosterone and 25-hydroxyvitamin D. No significant changes in antibody titres, hormone levels and the calculated parameters of thyroid homeostasis were observed in spironolactone-naïve men., What Is New and Conclusion: The obtained results indicate that spironolactone may exert an unfavourable effect on progression of autoimmune thyroiditis in men., (© 2019 John Wiley & Sons Ltd.)

PCOS is already a prevalent endocrinopathy in adolescent girls, and its prevalence is rising further since, in essence, it is the result of a mismatch between an energy-sparing (epi)genetic background and a (relatively) obesogenic environment. This mismatch results in an excess of fat storage in ectopic depots, notably in the liver and viscera (= hepato-visceral, or central fat). There is still no FDA-approved treatment for adolescent PCOS. The prime aim should be a preferential loss of central fat, through lifestyle measures. Failure to sustain these measures is frequent, and the standard approach is to add an estroprogestagen contraceptive, even for girls who do not need contraception. Treatment with SPIOMET, a low-dose combination of spironolactone (to antagonize androgen and mineralocorticoid effects, and to activate BAT thereby raising energy expenditure), pioglitazone (to raise circulating HMW adiponectin concentrations) and metformin, is an alternative approach that holds the potential to revert the PCOS phenotype., (© 2019 World Obesity Federation.)