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Evaluating the effects of sodium glucose co-transporter -2 inhibitors from a renin-angiotensin-aldosterone system perspective in patients infected with COVID-19: contextualizing findings from the dapagliflozin in respiratory failure in patients with COVID-19 study.
Moustafa, DA, Imran, Z, Ismail, R, Rayan, M, Gadeau, AP, Eldassouki, H, Abdulrahman, N, Mraiche, F
Molecular biology reports. 2022;(3):2321-2324
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Abstract
Numerous studies demonstrate parallels between CVD, type 2 diabetes mellitus (T2DM) and COVID-19 pathology, which accentuate pre-existing complications in patients infected with COVID-19 and potentially exacerbate the infection course. Antidiabetic drugs such as sodium-glucose transporter-2 (SGLT-2) inhibitors have garnered substantial attention recently due to their efficacy in reducing the severity of cardiorenal disease. The effect of SGLT-2 inhibitors in patients with COVID-19 remains unclear particularly since SGLT-2 inhibitors contribute to altering the RAAS cascade activity, which includes ACE-2, the major cell entry receptor for SARS-CoV2. A study, DARE-19, was carried out to unveil the effects of SGLT-2 inhibitor treatment on comorbid disease complications and concomitant COVID-19 outcomes and demonstrated no statistical significance. However, the need for further studies is essential to provide conclusive clinical findings.
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Sodium-Glucose Cotransporter Inhibitors in Non- Diabetic Heart Failure: A Narrative Review.
Dahal, R, Acharya, Y, Mukherjee, D
Cardiovascular & hematological disorders drug targets. 2021;(1):1-6
Abstract
BACKGROUND Heart failure (HF) is one of the leading public health problems with a substantial burden in the global healthcare system. Although significant efforts are based on prevention, early recognition, and proper management of HF, the worldwide surge of risk factors like hypertension, diabetes, and obesity has further complicated the existing problem. OBJECTIVE This study aims to define the role of the sodium-glucose cotransporter 2 (SGLT2) inhibitors in non-diabetic HF. METHODS We performed a comprehensive literature review to examine the available evidence in the clinical implications of SGLT2 inhibitors in non-diabetic HF using the online databases (PubMed and Embase). RESULTS We identified two RCTs-DAPA-HF and DEFINE-HF, which were conducted to analyze the net clinical benefit of dapagliflozin in non-diabetic HF patients. Although we could not study the composite effects of these studies due to the difference in outcome measures, the individual outcomes look promising. The number needed to treat (NNT) to prevent one primary event was 21 (95% CI: 15 to 38) in the DAPA study. In DEFINE HF study, responder analysis showed a significant proportion of patients in the treatment arm experienced improvements in the functional status with clinically meaningful improvement in KCCQ-OS by 3.7 points and KCCQ-CS by 4.6 points with NNT of 10 and 7, respectively, at 12 weeks. Both studies also showed low safety concerns in patients without T2D. CONCLUSION The outcomes of the two RCTs, DAPA-HF and DEFINE-HF, that studied the effects of SGLT2 inhibitors in non-diabetic HF showed promising clinical outcomes. Although we are waiting for other prospective RCTs to reflect similar results and safety profiles, it seems the SGLT2 inhibitors can have broader clinical implications in managing non-diabetic HF with improved cardiovascular outcomes.
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The Impact of Bisphenol A on Thyroid Function in Neonates and Children: A Systematic Review of the Literature.
Koutaki, D, Paltoglou, G, Vourdoumpa, A, Charmandari, E
Nutrients. 2021;(1)
Abstract
BACKGROUND Bisphenol A (BPA) is an endocrine-disrupting chemical widely used in plastic products that may have an adverse effect on several physiologic functions in children. The aim of this systematic review is to summarize the current knowledge of the impact of BPA concentrations on thyroid function in neonates, children, and adolescents. METHODS A systematic search of Medline, Scopus, Clinical Trials.gov, Cochrane Central Register of Controlled Trials CENTRAL, and Google Scholar databases according to PRISMA guidelines was performed. Only case-control, cross-sectional, and cohort studies that assessed the relationship between Bisphenol A and thyroid function in neonates and children aged <18 years were included. Initially, 102 articles were assessed, which were restricted to 73 articles after exclusion of duplicates. A total of 73 articles were assessed by two independent researchers based on the title/abstract and the predetermined inclusion and exclusion criteria. According to the eligibility criteria, 18 full-text articles were selected for further assessment. Finally, 12 full-text articles were included in the present systematic review. RESULTS The presented studies offer data that suggest a negative correlation of BPA concentrations with TSH in children, a gender-specific manner of action, and a potential effect on proper neurodevelopment. However, the results are inconclusive with respect to specific thyroid hormone concentrations and the effect on thyroid autoimmunity. CONCLUSION The potential negative effect of BPA in the developing thyroid gland of children that may affect proper neurodevelopment, suggesting the need to focus future research on designing studies that elucidate the underlying mechanisms and the effects of BPA in thyroid function in early life.
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Low carbohydrate diet while taking dapagliflozin: A case report and review of literature.
Paul, N, Jonklaas, J
Diabetes & metabolic syndrome. 2021;(1):361-363
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Fournier's gangrene and SGLT2 inhibitors: A case study.
García-García, A, Galeano-Valle, F, Nuevo-González, JA, Demelo-Rodríguez, P
Endocrinologia, diabetes y nutricion. 2020;(6):423-425
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Bisphenol A and Male Fertility: Myths and Realities.
Castellini, C, Totaro, M, Parisi, A, D'Andrea, S, Lucente, L, Cordeschi, G, Francavilla, S, Francavilla, F, Barbonetti, A
Frontiers in endocrinology. 2020;:353
Abstract
Bisphenol A (BPA) represents the main chemical monomer of epoxy resins and polycarbonate plastics. The environmental presence of BPA is widespread, and it can easily be absorbed by the human body through dietary and transdermal routes, so that more than 90% of the population in western countries display detectable BPA levels in the urine. As BPA is qualified as an endocrine disruptor, growing concern is rising for possible harmful effects on human health. This review critically discusses the available literature dealing with the possible impact of BPA on male fertility. In rodent models, the in vivo exposure to BPA negatively interfered with the regulation of spermatogenesis throughout the hypothalamic-pituitary-gonadal axis. Furthermore, in in vitro studies, BPA promoted mitochondrial dysfunction and oxidative/apoptotic damages in spermatozoa from different species, including humans. To date, the claimed clinical adverse effects on male fertility are largely based on the results from studies assessing the relationship between urinary BPA concentration and conventional semen parameters. These studies, however, produced controversial evidence due to heterogeneity in the extent of BPA exposure, type of population, and enrollment setting. Moreover, the cause-effect relationship cannot be established due to the cross-sectional design of the studies as well as the large spontaneous between- and within-subject variability of semen parameters. The best evidence of an adverse effect of BPA on male fertility would be provided by prospective studies on clinically relevant endpoints, including natural or medically assisted pregnancies among men either with different exposure degrees (occupational/environmental) or with different clinical conditions (fertile/subfertile).
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Severe euglycemic diabetic ketoacidosis of multifactorial etiology in a type 2 diabetic patient treated with empagliflozin: case report and literature review.
Sampani, E, Sarafidis, P, Dimitriadis, C, Kasimatis, E, Daikidou, D, Bantis, K, Papanikolaou, A, Papagianni, A
BMC nephrology. 2020;(1):276
Abstract
BACKGROUND Sodium-glucose co-transporter-2 (SGLT-2) inhibitors are a relatively novel class of oral medications for the treatment of Type 2 DM with a generally acceptable safety profile. However, these agents have been associated with rare events of a serious and potentially life-threatening complication named euglycemic diabetic ketoacidosis (euDKA). euDKA is not identical with the typical diabetic ketoacidosis, as it often presents with serious metabolic acidosis but only mild to moderate glucose and anion gap elevation. CASE PRESENTATION We report a case of a 51-year old female with Type 2 DM treated with an SGLT-2 inhibitor, developing severe metabolic acidosis with only mild blood glucose elevation after a routine surgery. A careful evaluation of involved factors led to the diagnosis of euDKA, followed by cautious application of simple therapeutic measures that resulted in complete restoration of acidosis and glycemic control in less than 48-h. CONCLUSIONS Euglycemic ketoacidosis is a rare but rather serious complication of SGLT-2 inhibitors use, often with a multifactorial etiology. Its atypical presentation requires a high level of awareness by physicians as early recognition of this complication can quickly and safely restore acid-base balance.
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Glucagon-Like Peptide 1 Receptor Agonists and Heart Failure: The Need for Further Evidence Generation and Practice Guidelines Optimization.
Khan, MS, Fonarow, GC, McGuire, DK, Hernandez, AF, Vaduganathan, M, Rosenstock, J, Handelsman, Y, Verma, S, Anker, SD, McMurray, JJV, et al
Circulation. 2020;(12):1205-1218
Abstract
With worsening epidemiological trends for both the incidence and prevalence of type 2 diabetes mellitus (T2DM) and heart failure (HF) worldwide, it is critical to implement optimal prevention and treatment strategies for patients with these comorbidities, either alone or concomitantly. Several guidelines and consensus statements have recommended glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter type 2 inhibitors as add-ons to lifestyle interventions with or without metformin in those at high atherosclerotic cardiovascular disease risk. However, these recommendations are either silent about HF or fail to differentiate between the prevention of HF in those at risk versus the treatment of individuals with manifest HF. Furthermore, these documents do not differentiate among those with different HF phenotypes. This distinction, even though important, may not be critical for sodium-glucose cotransporter type 2 inhibitors in view of the consistent data for benefit for both atherosclerotic cardiovascular disease- and HF-related outcomes that have emerged from the regulatory-mandated cardiovascular outcome trials for all sodium-glucose cotransporter type 2 inhibitors and the recent DAPA-HF trial (Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction)demonstrating the benefit of dapagliflozin on HF-related outcomes in patients with HF with reduced ejection fraction with or without T2DM. However, the distinction may be crucial for glucagon-like peptide-1 receptor agonists and other antihyperglycemic agents. Indeed, in several of the new statements, glucagon-like peptide-1 receptor agonists are suggested treatment not only for patients with T2DM and atherosclerotic cardiovascular disease, but also in those with manifest HF, despite a lack of evidence for the latter recommendation. Although glucagon-like peptide-1 receptor agonists may be appropriate to use in patients at risk for HF, mechanistic insights and observations from randomized trials suggest no clear benefit on HF-related outcomes and even uncertainty regarding the safety in those with HF with reduced ejection fraction. Conversely, theoretical rationales suggest that these agents may benefit patients with HF with preserved ejection fraction. Considering that millions of patients with T2DM have HF, these concerns have public health implications that necessitate the thoughtful use of these therapies. Achieving this aim will require dedicated trials with these drugs in both patients who have HF with reduced ejection fraction and HF with preserved ejection fraction with T2DM to assess their efficacy, safety, and risk-benefit profile.
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Dapagliflozin and cardiovascular outcomes in patients with Type 2 diabetes.
Al-Bazz, DY, Wilding, JP
Future cardiology. 2020;(2):77-88
Abstract
The relationship between cardiovascular disease, heart failure (HF) and Type-2 diabetes (T2DM) is widely recognized. Cardiovascular (CV) outcome trials are required for all new glucose-lowering agents to confirm safety with respect to CV risk. CV outcome trials with SGLT2i inhibitors have shown CV benefit, with reductions in major CV events and HF. This review focuses on the DECLARE-TIMI 58 trial with dapagliflozin in T2DM, which showed noninferiority for major adverse cardiovascular events and reduction in hospitalization for HF and associated CV mortality in a broad range of patients with T2DM. The DAPA-HF trial of dapagliflozin in people with HF with reduced ejection fraction with and without T2DM confirms benefits for those with HF.
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The impact of xenoestrogens on effectiveness of treatment for hormone-dependent breast cancer - current state of knowledge and perspectives for research.
Boszkiewicz, K, Sawicka, E, Piwowar, A
Annals of agricultural and environmental medicine : AAEM. 2020;(4):526-534
Abstract
INTRODUCTION Breast cancer is the most common cancer occurring in women and causing the highest number of deaths among them. The role of xenoestrogens has been the subject of many studies in the pathogenesis of breast cancer. Less is known about the impact of xenoestrogens on the effectiveness of hormone therapy used to treat breast cancer, and thus possible drug-xenostrogen interactions. OBJECTIVE The aim of this review is to summarize the current state of knowledge and present perspectives for further research on the impact of xenoestrogens on the effectiveness of drugs used in the treatment of hormone-dependent breast cancer. CURRENT STATE OF KNOWLEDGE Phytoestrogens, in particular flavonoid genistein, are the best studied group of xenoestrogens in terms of interaction with drugs used in the treatment of breast cancer, due to their frequent use, including their use in alleviating the adverse effects of hormone therapy. Analyzing the current state of knowledge, it seems that phytoestrogens intake should be avoided during conventional anti-cancer treatment. Of the other xenoestrogens, bisphenol A (BPA) is one of the best-tested compounds for interactions with drugs used to treat breast cancer. It has been shown that bisphenol A could reduced therapeutic effect of active tamoxifen metabolite and cytostatics used in breast cancer treatment. CONCLUSIONS Confirmation in clinical trials of the results obtained in vitro and in vivo tests, would enable the creation of specific recommendations for patients undergoing breast cancer treatment, especially hormone therapy. An area requiring further research is the analysis of the effects of xenoestrogens other than phytoestrogens, e.g. metalloestrogens, on the effects of drugs used in the treatment of breast cancer.