164 research outputs found
Effect of Bempedoic Acid on Serum Uric Acid and Related Outcomes: A Systematic Review and Meta-analysis of the available Phase 2 and Phase 3 Clinical Studies
No full textIntroduction: Bempedoic acid (ETC-1002) is a first-in-class lipid-lowering agent recently approved by the United States (US) Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for commercialization.
Objective: The aim was to assess, through a systematic review of the literature and a meta-analysis of the available phase 2 and phase 3 clinical studies, the effect of treatment with bempedoic acid on serum uric acid (SUA) concentration. Secondary outcomes were treatment-related variations in creatinine serum level and incidence of gout.
Methods: A systematic literature search in SCOPUS, PubMed Medline, ISI Web of Science and Google Scholar databases was conducted up to November 13th, 2019, in order to identify clinical trials potentially eligible for the meta-analysis. Effect sizes were expressed as absolute mean differences (MDs) and 95% confidence intervals (CIs).
Results: Data were pooled from four clinical studies comprising ten arms, which included overall 3369 subjects, with 2213 in the active-treatment arm and 1156 in the control one. Meta-analysis of data suggested that treatment with bempedoic acid is related to a significant increase in SUA (MD 0.73, 95% CI 0.54-0.91, P < 0.001), serum creatinine (MD 0.04, 95% CI 0.03-0.05, P < 0.001) and the incidence of gout (odds ratio 3.56, 95% CI 1.24-10.19, P = 0.018). The relatively small number of subjects involved in the studies and the exclusion of patients with renal impairment from the clinical trials are important limitations of the meta-analysis. However, our data indicate potential safety issues with bempedoic acid and suggest that further studies are performed both to elucidate the pathogenetic mechanisms underlying these associations and to verify the long-term safety of this treatment.
Conclusion: Bempedoic acid seems to have unfavourable effects on SUA, creatinine level and the incidence of gout. The ongoing Cardiovascular Outcomes Trial (CVOT) will explore the longer-term safety of treatment with bempedoic acid and clarify its effect on cardiovascular events and mortality
Correction to: Outcomes on safety and efficacy of left atrial appendage occlusion in end stage renal disease patients undergoing dialysis (Journal of Nephrology, (2021), 34, 1, (63-73), 10.1007/s40620-020-00774-5)
No full textThe article Outcomes on safety and efficacy of left atrial appendage occlusion in end stage renal disease patients undergoing dialysis, written by Simonetta Genovesi, Luca Porcu, Giorgio Slaviero, Gavino Casu, Silvio Bertoli, Antonio Sagone, Monique Buskermolen, Federico Pieruzzi, Giovanni Rovaris, Alberto Montoli, Jacopo Oreglia, Emanuela Piccaluga, Giulio Molon, Mario Gaggiotti, Federica Ettori, Achille Gaspardone, Roberto Palumbo, Francesca Viazzi, Marco Breschi, Maurizio Gallieni, Gina Contaldo, Giuseppe D’Angelo, Pierluigi Merella, Fabio Galli, Paola Rebora, Mariagrazia Valsecchi, and Patrizio Mazzone, was originally published electronically on the publisher’s internet portal on 6 June 2020 without open access. With the author(s)’ decision to opt for Open Choice the copyright of the article changed on 10 July 2020 to © The Author(s) 2020 and this article is licensed under a Creative Commons Attribution 4.0 International License (http://creat iveco mmons .org/licen ses/ by/4.0/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The original article has been updated
Uric acid in CKD: has the jury come to the verdict?
No full textEpidemiological studies show that hyperuricemia independently predicts the development of chronic kidney disease (CKD) in individuals with normal kidney function both in the general population and in subjects with diabetes. As a matter of fact, an unfavorable role of uric acid may somewhat be harder to identify in the context of multiple risk factors and pathogenetic mechanisms typical of overt CKD such as proteinuria and high blood pressure. Although the discrepancy in clinical results could mean that urate lowering treatment does not provide a constant benefit in all patients with hyperuricemia and CKD, we believe that the inconsistency in the results from available meta-analysis is mainly due to inadequate sample size, short follow-up times and heterogeneity in study design characterizing the randomized controlled trials included in the analyses. Therefore, available data support the view that hyperuricemia has a damaging impact on kidney function, while preliminary evidence suggests that treatment of so-called asymptomatic hyperuricemia may be helpful to slow or delay the progression of chronic kidney
Biblioteche e AI Literacy: alcune riflessioni sulle nuove competenze per la mediazione informativa
No full textIl tradizionale ruolo di mediazione informativa svolto dai/dalle bibliotecari/bibliotecarie, si arricchisce oggi di nuovi
contenuti che riguardano la divulgazione della conoscenza sull’uso il più possibile esperto degli strumenti basati
sull’intelligenza artificiale generativa. Questa nuova tecnologia, infatti, lungi da escludere i mediatori informativi,
quali sono i/le bibliotecari/e, e aggravare definitivamente le conseguenze del fenomeno della disintermediazione,
che ha caratterizzato questi decenni e ha messo in crisi la professione bibliotecaria, soprattutto nelle aree STEM e
Bio-Medical, può rappresentare un elemento di “riscatto” nei termini dell’evoluzione della professione verso una
dimensione spiccatamente divulgativa. A nostro avviso non esiste, o quasi, categoria professionale più adatta a
sanare i grandi vuoti di competenza e di conoscenza di un fenomeno così complesso, ma nello stesso tempo così
pervasivo come la diffusione dei tools di intelligenza artificiale, soprattutto nell’ambito frequentato dai/lle bibliotecari/
e, cioè l’informazione. Pensiamo a quanto possa essere utile “guidare” i ricercatori attraverso strumenti
che permettano loro di affidare all’AI gli aspetti più compilativi della loro attività di studio e ricerca, e permettere
loro di concentrarsi solo sugli aspetti speculativi e creativi, anche grazie ai suggerimenti delle macchine intelligenti.
E questo facendo solo il nostro consueto lavoro di fact checking e di verifica delle fonti informative, indipendentemente
dal contesto bibliotecario in cui ci si trovi a operare, oltre che dei contenuti proposti dall’AI che
possono essere falsati da bias e/o allucinazioni (che comunque dipendono sempre dall’interazione con gli umani).
La conoscenza dei tools - di cui ragioniamo nell’ultima parte di questo lavoro per dare concretezza ad un tema che
altrimenti rischia di essere troppo astratto per le nostre comunità di riferimento - si affianca così alla tradizionale
information literacy, una competenza che si pratica nelle nostre biblioteche e che trova così nuovi spunti per
aggiornarsi e continuare ad essere di supporto alla crescita informativa e intellettuale dei nostri utenti, per una
partecipazione sempre più consapevole ed esperta alla vita del XXI secolo
The liver and the kidney: two critical organs influencing the atherothrombotic risk in metabolic syndrome
No full textThe increased atherothrombotic risk in patients with metabolic syndrome (MetS) has been classically explained by the multiplicative effect of systemic concomitant pro-atherosclerotic factors. In particular, centripetal obesity, dyslipidaemia, glucose intolerance, hypertension (differently combined in the diagnosis of the disease) would be expected to act as classical cardiovascular risk conditions underlying accelerated atherogenesis. In order to better understand specific atherosclerotic pathophysiology in MetS, emerging evidence focused on the alterations in different organs that could serve as both pathophysiological targets and active players in the disease. Abnormalities in adipose tissue, heart and arteries have been widely investigated in a variety of basic research and clinical studies in MetS. In this narrative review, we focus on pathophysiological activities of the liver and kidney. Considering its key role in metabolism and production of soluble inflammatory mediators (such as C-reactive protein [CRP]), the liver in MetS has been shown to be altered both in its structure and function. In particular, a relevant amount of the fat accumulated within this organ has been shown to be associated with different degrees of inflammation and potential insulin resistance. In humans, non-alcoholic fatty liver disease (NAFLD) has been described as the hepatic manifestation of MetS. In an analogous manner, epidemiological evidence strongly suggested a "guilty" association between MetS and chronic kidney disease (CKD). Some biomarkers of hepatic (such as C-reactive protein, TNF-alpha or other cytokines) and renal diseases (such as uric acid) associated with MetS might be particularly useful to better manage and prevent the atherothrombotic risk
The URRAH study
No full textBACKGROUND: Uric acid has long been considered responsible for a single specific disease, namely gout. In recent years, novel knowledge has emerged linking serum uric acid with a variety of conditions and related risk factors, from hypertension, metabolic syndrome, and type 2 diabetes, to fatal/nonfatal cardiovascular diseases and all-cause death, with the underlying mechanisms involving disrupted neurohormonal and metabolic signaling as well as oxidative stress and inflammation. Importantly, the cut-off value of serum uric acid that predicts the risk of incident events is within the range of normality and below the threshold for increased risk of gout. A large contribution to the advancement in knowledge in the cardiovascular implications of uric acid derives from the Italian study URic acid Right for heArt Health (URRAH). METHODS: The URRAH study is an Italian nationwide, multicenter retrospective, observational cohort study combining data from outpatients attending hypertension clinics, as well as individuals recruited in prospective observational cohort studies with a follow-up period of at least 20 years up to July 31st, 2017. Data were retrospectively collected from different databases. At the end of the follow-up, the following hard endpoints were evaluated: fatal myocardial infarction; non-fatal acute myocardial infarction; heart failure; fatal stroke; non-fatal stroke; coronary revascularization. RESULTS: A total of 22,714 subjects were included in the analysis. During a median follow-up time of 134 months, a total of 3279 deaths were recorded, of which 1571 were due to cardiovascular causes. Multivariate Cox regression analyses identified an independent association between serum uric acid concentrations and both total (HR=1.53, 95% CI 1.21-1.93, P<0.001) and cardiovascular deaths (HR=2.08, 95% CI 1.146-2.97; P<0.001). Of note, the cut-off values of serum uric acid that were identified as those able to predict total mortality were largely within the normal range (4.7 mg/dL, 95% CI 4.3-5.1 mg/dL). Similarly, the cut-off value that better predicted cardiovascular death was within the normal range (5.6 mg/dL, 95% CI 4.99-6.21 mg/dL). The information on serum uric acid levels provided a significant net reclassification improvement of 0.26 and 0.27 over the Heart Score risk chart for total and cardiovascular mortality, respectively (P<0.001). Serum uric acid levels ≥4.7 or <4.7 mg/ dL incrementally predicted all-cause mortality over the Heart Score. CONCLUSIONS: The results of studies from the URRAH database further strengthen the role of uric acid in cardiovascular disease, including heart failure, and total mortality. The identified cut-off values support clinicians in investigating serum uric acid levels in their patients and to consider uric acid as an additional cardiovascular risk factor. Taken together, the published papers deriving from the URRAH database emphasize the role of uric acid in favoring cardiovascular events, and strongly suggest the existence of “grey” areas, i.e. close but lower than the “traditional” threshold for hyperuricemia, which deserve further characterization
Nutritional Challenges in Pregnant Women with Renal Diseases: Relevance to Fetal Outcomes
No full textPregnancy in women affected by chronic kidney disease (CKD) has become more common in recent years, probably as a consequence of increased CKD prevalence and improvements in the care provided to these patients. Management of this condition requires careful attention since many clinical aspects have to be taken into consideration, including the reciprocal influence of the renal disease and pregnancy, the need for adjustment of the medical treatments and the high risk of maternal and obstetric complications. Nutrition assessment and management is a crucial step in this process, since nutritional status may affect both maternal and fetal health, with potential effects also on the future development of adult diseases in the offspring. Nevertheless, few data are available on the nutritional management of pregnant women with CKD and the main clinical indications are based on small case series or are extrapolated from the general recommendations for non-pregnant CKD patients. In this review, we discuss the main issues regarding the nutritional management of pregnant women with renal diseases, including CKD patients on conservative treatment, patients on dialysis and kidney transplant patients, focusing on their relevance on fetal outcomes and considering the peculiarities of this population and the approaches that could be implemented into clinical practice
The role of uric acid in renal damage: A history of inflammatory pathways and vascular remodeling
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