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Background & Aim: Liver fibrosis is the strongest predictor of liver-related mortality in many chronic liver diseases. NT-ProBNP is independently associated with cardiovascular mortality in general population settings. Here, we evaluate the relative contribution of non-invasively identified liver fibrosis and NT-ProBNP on all-cause and cardiovascular mortality in patients with metabolic (dysfunction)-associated steatotic liver disease (MASLD)., Methods and Results: Serum NT-ProBNP levels were measured in 4229 patients with MASLD from the general population without a known history of heart failure that participated in the 1999-2004 cycles of the National Health and Nutrition Examination Survey. Presence of liver fibrosis was estimated using the Fibrosis-4 index (FIB-4). We applied Cox proportional hazard models adjusted for cardiovascular risk factors to evaluate the association between NT-ProBNP and FIB-4 levels and all-cause and cardiovascular mortality through December 2019. Mortality was lower for participants with normal levels of both biomarkers, intermediate if a single biomarker was elevated and highest when both were above the chosen threshold. In the multivariable-adjusted models, both elevated FIB-4 (≥2.67) and elevated NT-ProBNP levels (≥125 pg/ml) were independently associated with higher risks of all-cause mortality (HR 2.2, 95 % CI 1.5-3.2 and HR 1.6, 95 % CI 1.4-2.0, respectively) and cardiovascular mortality (HR 2.1, 95 % CI 1.2-3.7 and HR 2.1, 95 % CI 1.5-2.9, respectively). The associations remained consistent in subgroup analyses based on sex, obesity and age., Conclusions: Both FIB-4 and NT-ProBNP are independently associated with higher mortality in patients with MASLD. Their combined use might prove useful to risk-stratify patients in clinical practice., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier B.V.)

Competing Interests: Conflict of interest None declared.

Objectives: To assess whether the use of the revised Cochrane risk of bias tool for randomized trials (RoB2) in systematic reviews (SRs) adheres to RoB2 guidance., Methods: We searched MEDLINE, Embase, Cochrane Library from 2019 to May 2021 to identify SRs using RoB2. We analyzed methods and results sections to see whether risk of bias was assessed at outcome measure level and applied to primary outcomes of the SR as per RoB2 guidance. The relation between SR characteristics and adequacy of RoB2 use was examined by logistic regression analysis., Results: Two hundred-eight SRs were included. We could assess adherence in 137 SRs as 12 declared using RoB2 but actually used RoB1 and 59 did not report the number of primary outcomes. The tool usage was adherent in 69.3% SRs. Considering SRs with multiple primary outcomes, adherence dropped to 28.8%. We found a positive association between RoB2 guidance adherence and the methodological quality of the reviews assessed by AMSTAR2 (p-for-trend 0.007). Multivariable regression analysis suggested journal impact factor [first quartile vs. other quartiles] was associated with RoB2 adherence (OR 0.34; 95% CI: 0.16-0.72)., Conclusions: Many SRs did not adhere to RoB2 guidance as they applied the tool at the study level rather than at the outcome measure level. Lack of adherence was more likely among low and very low quality reviews., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Aims: Glycated albumin (GA) reflects short-term glycemic control, but few data are available on its association with hard clinical outcomes. The purpose of this study is to evaluate the association between GA levels and all-cause and cardiovascular mortality in people with and without a previous diagnosis of diabetes., Methods and Results: Serum GA levels were measured in 12147 people from the general population (1319 with and 10828 without diabetes) that participated in the 1999-2004 cycles of the National Health and Nutrition Examination Survey (NHANES). We evaluated the association between GA and all-cause and cardiovascular mortality through December 2015 by linking NHANES data with data from the National Death Index. Associations were compared with those observed for hemoglobin A1c (HbA1c). After a median follow-up of 13 years, 2785 participants (619 with and 2166 without diabetes) died, 651 of cardiovascular causes. Multivariable-adjusted Cox proportional hazard models showed that higher baseline GA levels were significantly associated with a higher incidence of both outcomes in participants with (all-cause: HR 1.03, 95% CI 1.01-1.04; cardiovascular: HR 1.04, 95% CI 1.02-1.07) and without diabetes (all-cause: HR 1.05, 95% CI 1.03-1.08; cardiovascular: HR: 1.08, 95% CI 1.02-1.14); on the other hand, we found a trend for increased mortality with increasing HbA1c levels in patients with known diabetes, but not in participants without., Conclusions: For a novel measure of hyperglycemia to be considered useful, its association with hard, long term clinical outcomes is of great importance. We showed that GA is associated with mortality in the general population independently of a previous diagnosis of diabetes., Competing Interests: Conflict of interest All authors declare no conflicts of interest related to this study., (Copyright © 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: The aim of this study is to evaluate trends in heart failure (HF) prevalence, impact of accompanying risk factors and use of effective therapeutic regimens during the last two decades in the general adult US population., Methods: We analyzed data obtained from the 1999-2018 cycles of the National Health and Nutrition Examination Survey (NHANES). Among a total of 34,403 participants 40 years or older who attended the mobile examination center visit, 1690 reported a diagnosis of HF. Trends in participant features across calendar periods were assessed by linear regression for continuous variables and logistic regression for binary variables., Results: Prevalence of self-reported HF did not change significantly from 1999 to 2002 to 2015-2018 (~3.5%), while obesity and diabetes showed a progressive increase in prevalence, affecting ~65% and ~ 45% of patients with HF in the most recent calendar period, respectively. In parallel, use of glucose lowering drugs (especially metformin and insulin) as well as statins increased from 1999 to 2010, with significant improvement of the lipid control. A modest improvement in blood pressure control was achieved in association with a significant increase in the use of angiotensin receptor blockers and beta-blockers., Conclusions: In the last 20 years, the prevalence of HF in US adults remained stable, while both obesity and diabetes increased, with the two conditions affecting half of patients with HF. Improvements in the control of dyslipidemia and, to a lesser extent, blood pressure, was detected; nonetheless, a significant gap remains in guideline-directed use of HF and diabetes medications., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Few population-based studies have investigated the association between body fat distribution and the risk of nonalcoholic fatty liver disease (NAFLD) and significant liver fibrosis., Objectives: We aimed to evaluate the relations of total body fat and body fat distribution with NAFLD in the general US population., Methods: This is a cross-sectional, population-based study based on the 2017-2018 cycle of the NHANES. Participants aged 18-59 y without known liver conditions or significant alcohol consumption were studied by DXA and vibration-controlled transient elastography to assess body composition and liver steatosis and fibrosis, respectively. Multivariable logistic regression analysis was performed to evaluate the contribution of BMI and android:gynoid ratio (A:G ratio) to the prevalence of liver steatosis and fibrosis in males and females., Results: Weighted prevalence of steatosis was 41.5% and 29.9% among the 1115 males and 1113 females included in the study, respectively, whereas 7.0% of males and 4.0% of females had elastographic evidence of significant liver fibrosis. After adjustment for age, race-Hispanic origin, diabetes, cigarette smoke, and BMI, a higher A:G ratio was associated with increased odds of steatosis in both males (OR: 1.79; 95% CI: 1.07, 2.99; P = 0.029) and females (OR: 1.95; 95% CI: 1.11, 3.41; P = 0.023). Conversely, a significant association between A:G ratio and liver fibrosis was identified in females (OR: 2.09; 95% CI: 1.11, 3.97; P = 0.026), but not in males (OR: 0.56; 95% CI: 0.29, 1.08; P = 0.078)., Conclusions: Independently from BMI, an android fat deposition pattern is associated with increased prevalence of NAFLD in both sexes, whereas the effect on fibrosis was only evident in females., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) are frequent and progressive conditions that share traditional risk factors: obesity, type 2 diabetes and hypertension., Aims: To evaluate whether an independent relationship exists between liver steatosis and fibrosis and different CKD phenotypes., Methods: Cross sectional study based on data from the 2017-18 cycle of the National Health and Nutrition Examination Survey. Vibration controlled transient elastography (VCTE) was performed in a US representative sample allowing the simultaneous assessment of liver steatosis (CAP: controlled attenuation parameter) and fibrosis (LSM: liver stiffness measurement) and their relationships with CKD phenotypes (albuminuria and reduced estimated glomerular filtration rate, eGFR)., Results: 4746 adult participants had a complete VCTE exam. Prevalence of liver steatosis and significant fibrosis was 33.7% (95%CI: 30.9-36.6%) and 8.9% (95%CI: 7.5-10.5%), respectively. Logistic regression analysis showed that liver fibrosis, but not steatosis, was associated with albuminuria (OR 2.19, 95%CI: 1.49-3.20) and albuminuria or reduced eGFR (OR 2.18, 95%CI: 1.59-3.00) also when adjusted for age, sex, ethnicity, BMI, diabetes, blood pressure categories, glycated haemoglobin, use of renin-angiotensin-aldosterone system blockers and CAP., Conclusions: In the general US population liver fibrosis assessed using VCTE is associated with CKD, and in particular with the albuminuric phenotype, regardless of traditional risk factors., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest related to this study., (Copyright © 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: Seasonal variations in several risk factors for cardiovascular events (CVD) were described. Here, we evaluate the impact of seasonal variations in blood pressure (BP), lipid profile and glycemic control on estimated CVD risk in patients with type 2 diabetes (T2D)., Methods and Results: Retrospective monocentric study of patients with T2D who were visited at least once in the winter period and once in the summer period, less than 8 months apart, for which data related to systolic (S) BP, diastolic (D) BP, body mass index, glycosylated hemoglobin (HbA1c), total cholesterol, HDL cholesterol and smoking habit were available on both occasions. The 10-year CVD risk was calculated using the UKPDS risk engine and the ASCVD risk estimator. As many as 411 patients were included in the study. Significant within-patient differences between summer and winter were found for the absolute risk of events assessed with both calculators (Δs-w UKPDS-CHD: -1.33%, Δs-w UKPDS-Stroke: -0.84%, Δs-w ASCVD: -2.21%). The seasonal change in SBP was the main responsible for the change in risk estimated with both the UKPDS-Stroke (r 2  = 0.43) and the ASCVD (r 2  = 0.50) scores, while the change in total cholesterol was the main determinant of the change in risk for the UKPDS-CHD (r 2  = 0.34). A significant correlation was identified between changes in temperature and changes in SBP (ρ = 0.130, p = 0.008), but not in other risk factors., Conclusions: Seasonal variations in the classic CVD risk factors influence the risk estimated using validated calculators., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest related to this study., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Sodium glucose transporter 2 inhibitors (SGLT2-i) reduce renal and cardiovascular events in patients with type 2 diabetes (T2D) and their use is recommended by the 2020 KDIGO guidelines in patients with T2D and chronic kidney disease (CKD). The aim of this study is to estimate the proportion of patients with T2D and CKD in the US that should be treated with these agents for renal and cardiovascular protection., Methods: We conducted a retrospective analysis of 2005-2018 National Health and Nutrition Examination Survey (NHANES) data. We focused on participants with a prior diagnosis of diabetes or that met diagnostic criteria for diabetes during the survey, with the exclusion of probable type 1 diabetic patients. Inclusion criteria for completed and ongoing renal and cardiovascular outcome trials in patients with CKD were applied., Results: We estimated that 35.3% of patients with T2D in the US (projected to 8.96 million) should be treated with SGLT2-i according to the 2020 KDIGO guidelines. Moreover, 2.9-10.1% (projected to 0.75-2.55 million) met the inclusion criteria for dedicated kidney outcome trials, which were focused on a population of individuals with proteinuria., Conclusions: About a third of patients with T2D in the US should be treated with an SGLT2-i. While compelling evidence of renal protection is present for patients with proteinuria, all patients with CKD obtain a cardiovascular benefit with this class of drugs., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The advent of Sodium Glucose Transporter 2-inhibitors (SGLT2-i) in recent years gave endocrinologists the opportunity to actively treat and prevent heart failure (HF) in patients with type 2 diabetes (T2DM). While the relationship between T2DM and HF has been extensively reviewed, previous works focused mostly on epidemiology, pathophysiology and treatment of HF in T2DM. The aim of our work was to aid health care professionals in identifying individuals at high risk for this dreadful complication. Recent guidelines recommend to use drugs with proven cardiovascular benefits (Glucagon-like peptide-1 receptor agonists (GLP1-RA) and SGLT2-i) in patients with previous cardiovascular disease (CVD) and to prefer SGLT2-i in patients with known HF. In everyday clinical practice, the choice between these two drug classes in patients without known HF or atherosclerotic CVD is mostly arbitrary and based on the side effect profile. Recently, risk stratification tools to estimate HF incidence have been developed in order to guide treatment with a view to bring precision medicine into diabetes care. With this purpose, we provide a review of the tools able to predict HF incidence for patients in primary CVD prevention as well as risk of future hospitalizations for patients with known HF., (Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Arsenic (As) speciation in muscle tissues of freshwater fish was investigated with special emphasis on extraction yields and mass balances. For the quantification of water-soluble As compounds, samples were extracted using a 1:1 (v/v) methanol/water mixture. Various extraction parameters, such as extraction volume, number of additional extractions, intermediate and final volume in sample preconcentration were optimized so as to improve the extraction efficiency. Arsenic compounds were determined by HPLC with online ICP-MS, using both cation and anion exchange separation. The species studied were eel (Anguilla anguilla L.), flathead grey mullet (Mugil cephalus L.), chub (Leuciscus cephalus L.), and carp (Cyprinus carpio L.). Mean total As concentrations ranged from 354 microg kg(-1) dry weight (carp) to 1804 microg kg(-1) dry weight (mullet). Under optimized conditions, the percentage of total As extracted ranged from 64% for carp, to 82%, 84%, and 89% for grey mullet, eel and chub, respectively. Extraction of lipid-rich eel with n-hexane recovered some additional 3% of total As. The sizeable effect of sample matrix on HPLC retention time of some organoarsenicals in gradient elution cation exchange chromatography was exploited to achieve separation of coeluting compounds by analysing the same sample at different dilutions. The recovery of As from chromatographic columns was 101%, 102%, 103% and 104% for carp, chub, mullet and eel, respectively, indicating that no As was retained during chromatography. Arsenobetaine (AB) was the dominating As compound, but several other arsenicals, including arsenous acid (Asiii), arsenic acid (Asv), methylarsonic acid (MMA), dimethylarsinic acid (DMA), trimethylarsine oxide (TMAO), arsenocholine ion (AC), tetramethylarsonium ion (TETRA), oxo-arsenosugar-glycerol (AS1), oxo-arsenosugar-phosphate (AS2), oxo-arsenosugar-sulfate (AS4), thio-arsenosugar-phosphate (ThioAS2), and three unknown As compounds, were found. Arsenic speciation in carp was different compared to the other fish species, and a lower proportion of AB along with a high contribution of AS2 and ThioAS2 was found. DMA and TMAO were noteworthy minor compounds in eel and carp, respectively. Arsenic speciation and the chemical composition of fish muscle both appeared to affect the extraction yield., ((c) 2009 Elsevier B.V. All rights reserved.)