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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.

Nonalcoholic fatty liver disease (NAFLD) affects a quarter of the adult world population and the degree of liver fibrosis represents the best predictor of the development of liver-related outcomes. Easily applicable and well performing non-invasive fibrosis tests can overcome the limitations of liver biopsy and are of paramount importance to identify at-risk subjects in clinical practice. While tests with optimal performance and ease of use do not exist at this stage, available markers can be divided in three broad groups: simple serum tests, complex serum tests and elastographic methods. Simple scores (such as Fibrosis-4 and NAFLD Fibrosis Score) are based on readily available biochemical data and clinical features, while complex/proprietary tests (such as Fibrotest, Enhanced Liver Fibrosis and Hepascore) directly measure markers of fibrogenesis and fibrolysis, but have higher costs. Elastography techniques estimate the degree of fibrosis from liver stiffness and are based on either ultrasound or magnetic resonance (MR) imaging. MR elastography has better performance compared with sonographic techniques and is not affected by obesity and inflammation, but is highly costly and less available. In general, non-invasive tests are able to exclude the presence of fibrosis, but their positive predictive value is low to moderate and they lead to a high number of indeterminate results. In this context, a combination of different tests might increase accuracy while reducing gray-zone results. Their ability to predict future events and response to treatment is suboptimal and needs to be studied further. Finally, recent studies have tried different approaches, spanning from “omics” to the microbiome and micro-RNAs, with some promising results.

Objective. Problematic Social Media Use (PSMU) has an addictive potential for young users. The aim of this study was to show the prevalence of PSMU across Italian regions and its association with health complaints. Materials and methods. Data are gathered from the Italian 2018 Health Behaviour in School-aged Children survey using a representative sample of Italian adolescents aged 11, 13 and 15 years (50.6% males). Participants completed self-administered questionnaires assessing PSMU and health complaints. Results. PSMU affects 8.9% adolescents in Italy and the prevalence is quite consistent across regions. 13-year-olds girls showed the highest percentage of PSMU (13%). Problematic users of social media are more likely to report multiple somatic (OR = 1.84 [95% CI 1.82-1.85]) and psychological (OR = 2.60 [95% CI 2.58-2.63]) symptoms. Conclusions. PSMU represents a widespread problem in Italy. National prevention interventions are needed in order to promote a positive use of social media.

Objective. The aim is to describe dietary habits and their association with socio-demographic characteristics in a large nationally representative sample of Italian adolescents aged 11, 13 and 15 years. Materials and methods. Data from the 2018 Italian Health Behaviour in School-aged Children (HBSC) survey on 58,976 adolescents were analysed to determine eating habits. Logistic regression was used to investigate the association between incorrect dietary habits and potential predictors. Results. 38.3% of boys and 48.1% of girls skipped breakfast and 54.1% did not consume fruit and/or vegetables daily. 15.9% of boys and 11.3% of girls drank carbonated-sugary beverages at least once a day. Incorrect dietary habits were more common among boys, adolescents with lower socio-economic conditions, residents in Southern Italy and those spending more time watching TV. Italian adolescents were more likely to have incorrect dietary habits compared with those from most other countries involved in 2018 HBSC. Conclusions. Action is needed to improve dietary habits among adolescents.

The spatial distribution of selected metals (Fe, Ni, Mn, Zn, Cu, Pb, Hg and Cd) and their partition in the different chemical forms (speciation) were determined in benthic sediments from Mar Piccolo, Taranto (Ionic Sea, Southern Italy). The aim of this study was to assess the degree of sediment contamination and bioavailability of metals, very important for Italian mussel culture, in a semi-enclosed marine ecosystem. In sediments, grain size distribution, total organic carbon (TOC), and humic (HA) and fulvic (FA) acids contents were also determined. The compounds TOC, HA and FA, in fact, have a great influence on metal complexation. High concentrations of copper, lead, zinc and mercury were found, especially in sediments of the first inlet of Mar Piccolo. Statistical analysis of results shows significant correlation among Cu, Pb and Zn concentrations and the influence of organic matter on the sediment distribution of Cu, Pb and Zn. Metal speciation analysis, carried out with sequential extraction method, shows that Fe and Ni are present in sediments mainly as sulphides. Mn and Pb are present principally in an ion-exchangeable form or bound to carbonate and Cu is associated to organic matter. Metal pollution index (MPI), calculated as a weighed mean of the metal contamination factors in each station, shows that with regard to Cu, Ni, Pb and Zn, some stations investigated are unpolluted (MPI

Background: The progress of digital transformation in clinical practice opens the door to transforming the current clinical line for liver disease diagnosis from a late-stage diagnosis approach to an early-stage based one. Early diagnosis of liver fibrosis can prevent the progression of the disease and decrease liver-related morbidity and mortality. We developed here a machine learning (ML) algorithm containing standard parameters that can identify liver fibrosis in the general US population.Materials and methods: Starting from a public database (National Health and Nutrition Examination Survey, NHANES), representative of the American population with 7265 eligible subjects (control population n = 6828, with Fibroscan values E < 9.7 KPa; target population n = 437 with Fibroscan values E >= 9.7 KPa), we set up an SVM algorithm able to discriminate for individuals with liver fibrosis among the general US population. The algorithm set up involved the removal of missing data and a sampling optimization step to managing the data imbalance (only similar to 5 % of the dataset is the target population).Results: For the feature selection, we performed an unbiased analysis, starting from 33 clinical, anthropometric, and biochemical parameters regardless of their previous application as biomarkers of liver diseases. Through PCA analysis, we identified the 26 more significant features and then used them to set up a sampling method on an SVM algorithm. The best sampling technique to manage the data imbalance was found to be oversampling through the SMOTE-NC. For final model validation, we utilized a subset of 300 individuals (150 with liver fibrosis and 150 controls), subtracted from the main dataset prior to sampling. Performances were evaluated on multiple independent runs.Conclusions: We provide proof of concept of an ML clinical decision support tool for liver fibrosis diagnosis in the general US population. Though the presented ML model represents at this stage only a prototype, in the future, it might be implemented and potentially applied to program broad screenings for liver fibrosis.

BACKGROUND Observational studies showed that exposure to exogenous insulin increases fracture risk. However, it remains unclear whether the observed association is a function of the severity of underlying type 2 diabetes mellitus, complications, therapies, comorbidities, or all these factors combined. That being so, and because of the relative infrequency of these events, it is important to study this further in a large-database setting. QUESTION/PURPOSES: (1) Is switching from oral antidiabetic agents to insulin associated with an increased fracture risk? (2) How soon after switching does the increased risk appear, and for how long does this increased risk persist? METHODS Data from healthcare utilization databases of the Italian region of Lombardy were used. These healthcare utilization databases report accurate, complete, and interconnectable information of inpatient and outpatient diagnoses, therapies, and services provided to the almost 10 million residents in the region. The 216,624 patients on treatment with oral antidiabetic therapy from 2005 to 2009 were followed until 2010 to identify those who modified their antidiabetic therapy (step 1 cohort). Among the 63% (136,307 patients) who experienced a therapy modification, 21% (28,420 patients) switched to insulin (active exposure), and the remaining 79% (107,887 patients) changed to another oral medication (referent exposure). A 1:1 high-dimension propensity score matching design was adopted for balancing patients on active and referent exposure. Matching failed for 3% of patients (926 patients), so the cohort of interest was formed by 27,494 insulin-referent couples. The latter were followed until 2012 to identify those who experienced hospital admission for fracture (outcome). A Cox proportional hazard model was fitted to estimate the hazard ratio (HR) for the outcome risk associated with active-exposure (first research question). Between-exposure comparison of daily fracture hazard rates from switching until the 24 successive months was explored through the Kernel-smoothed estimator (second research question). RESULTS Compared with patients on referent exposure, those who switched to insulin had an increased risk of experiencing any fracture (HR = 1.5 [95% CI 1.3 to 1.6]; p < 0.001). The same risk was observed for hip and vertebral fractures, with HRs of 1.6 (95% CI 1.4 to 1.8; p < 0.001) and 1.8 (95% 1.5 to 2.3; p < 0.001), respectively. Differences in the daily pattern of outcome rates mainly appeared the first 2 months after switching, when the hazard rate of patients on active exposure (9 cases for every 100,000 person-days) was higher than that of patients on referent exposure (4 cases for every 100,000 person-days). These differences persisted during the remaining follow-up, though with reduced intensity. CONCLUSIONS We found quantitative evidence that switching from oral antidiabetic therapy to insulin is associated with an increased fracture risk, mainly in the period immediately after the start of insulin therapy. The observed association may result from higher hypoglycemia risk among patients on insulin, which leads to a greater number of falls and resulting fractures. However, although our study was based on a large sample size and highly accurate data, its observational design and the lack of clinical data suggest that future research will need to replicate or refute our findings and address the issue of causality, if any. Until then, though, prescribers and patients should be aware of this risk. Careful control of insulin dosage should be maintained and measures taken to reduce fall risk in these patients. LEVEL OF EVIDENCE Level III, therapeutic study.

The central function of the liver in the regulation of the metabolisms of hormones and nutrients makes it an integral part of the endocrine system. In everyday clinical practice, the endocrinologist usually encounters patients with altered liver function tests. This condition might be a cause or a consequence of the endocrine disease (e.g. type 2 diabetes mellitus, polycystic ovary syndrome), an associated condition as in the case of concomitant autoimmune diseases, a consequence of a specific pharmacological treatment, or an unrelated condition. In this chapter, we focus on the most common causes of alteration of liver function tests and provide indications on how to perform the first assessment of liver disease and when to refer patients to a hepatologist.

Introduction Serum neurofilament light chain (sNfL) levels are biomarkers of neuro-axonal injury in multiple neurological diseases. Little is known on their potential role as prognostic markers in people without known neurological conditions. Objective The aim of this study is to evaluate the association between sNfL levels and all-cause mortality in a general population setting. Methods sNfL levels were measured in 2071 people aged 25–75 years from the general US population that participated in the 2013–2014 cycles of the National Health and Nutrition Examination Survey (NHANES). Cognitive function was evaluated in a subset of participants aged 60–75 years using the Consortium to Establish a Registry for Alzheimer’s Disease-Word Learning test, the Animal Fluency test and the Digit Symbol Substitution test. We applied Cox proportional hazard models adjusted for several potential confounders to evaluate the association between sNfL and all-cause mortality through December 2019 by linking NHANES data with data from the National Death Index. Results In a cross-sectional analysis, higher sNfL levels were associated with worse performance in all three cognitive function tests. Over a median follow-up of 6.1 years, 85 participants died. In a multivariable model adjusted for age, sex, race-ethnicity, diabetes, chronic kidney disease, harmful alcohol consumption, cigarette smoke and prevalent cardiovascular disease, higher sNfL levels were significantly and positively associated with all-cause mortality (HR per unit increase in log-transformed sNfL: 2.46, 95% CI 1.77–3.43, p Conclusion We found a positive association between sNfL levels and mortality in the general US population. Further studies are needed to understand the biological mechanisms underlying this association.

Aims: Evidence on the role of 25-Hydroxyvitamin D (25(OH)D) in the occurrence and progression of nonalcoholic fatty liver disease (NAFLD) is conflicting and population-based data are scarce. Here, we assess the association between 25(OH)D levels, NAFLD and liver fibrosis in the general population. Materials and Methods: This is an analysis of data from the 2017–2018 cycle of the National Health and Nutrition Examination Survey. We included adult participants with available data on vibration-controlled transient elastography (VCTE) and without viral hepatitis and significant alcohol consumption. Steatosis and fibrosis were diagnosed by the median values of controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), respectively. 25(OH)D was measured by high performance liquid chromatography-tandem mass spectrometry. Results: A total of 3970 participants (1928 men and 2042 women) were included in the study. The prevalence of NAFLD (CAP ≥ 274 dB/m) and significant liver fibrosis (LSM ≥ 8 kPa) were 41.7% (95% CI 39.4–44.0) and 8.4% (95% CI 7.0–9.9), respectively, while 21.1% (95% CI 17.3–25.4) of participants had low 25(OH)D levels (

Context Serum neurofilament light chain (sNfL) levels are biomarkers of neuroaxonal injury in multiple neurological diseases. Objective Given the paucity of data on the distribution of sNfL levels in the general population, in the present study we identified predictors of sNfL levels in a community setting and investigated the association between diabetes and sNfL. Methods sNfL levels were measured in 2070 people aged 20 to 75 years from the general US population (275 with and 1795 without diabetes) that participated in the 2013-2014 cycle of the National Health and Nutrition Examination Survey. We evaluated the association between diabetes and sNfL levels after adjustment for age, sex, race-ethnicity, alcohol use, and kidney function using a multivariable linear regression model. Cognitive function was evaluated in a subset of participants aged 60 to 75 years using the Consortium to Establish a Registry for Alzheimer's Disease-Word Learning test, the Animal Fluency test, and the Digit Symbol Substitution test. Results The weighted prevalence of diabetes was 10.4% (95% CI, 9.0-11.9). In each age stratum, patients with diabetes exhibited higher sNfL levels compared with nondiabetic participants. Age, proportion of males, prevalence of diabetes, and homeostatic model of insulin resistance increased progressively across quartiles of sNfL levels in the overall population, whereas estimated glomerular filtration rate (eGFR) showed an opposite trend. In the multivariable model, age, sex, eGFR, alcohol use and diabetes were significantly associated with sNfL levels. Moreover, higher sNfL levels were associated with worse performance in all 3 cognitive function tests. Conclusion Diabetes is associated with higher sNfL. Further large-scale and prospective studies are needed to replicate our results and evaluate the ability of sNfL to predict the incidence of neuropathy and dementia in this patient population.

A large number of epidemiological studies identified diabetes as an independent risk factor for cardiovascular (CV) events, the excess risk being proportional to blood glucose levels. Based on these data, several large randomized clinical trials (RCTs) were initiated to evaluate whether better glycemic control obtained with medications would lead to a lower incidence of CV events. Although results of the single RCTs were inconsistent, meta-analytic evidence suggests that the achievement of a more ambitious glycemic target is able to reduce both micro- and macro-vascular complications, and that this protective effect is evident only if patients are followed for a long period of time (~10 years). It also became clear that apart from the achieved glycemic levels, the use of specific medications could have an impact on CV outcomes. Regulatory agencies started to request that in order to receive approval for commercialization, candidate drugs for the treatment of type 2 diabetes had to have a safe CV profile. As a consequence, a considerable number of CV safety trials were conducted with several classes of drugs. Among them, sodium-glucose transporter 2 inhibitors (SGLT2-i) and glucagon like peptide 1 receptor agonists (GLP1-RA) were able to reduce the incidence of CV events compared with placebo, an effect that was largely independent from their glucose-lowering ability. These results profoundly changed clinical practice guidelines from international societies, which now recommend the use of these drugs independently from glycemic control for their protective properties on CV and renal outcomes.

Aim: Identifying patients with fibrotic nonalcoholic steatohepatitis (NASH) is crucial in order to refer them to specialist care as fibrotic NASH represents one of the major inclusion criteria for clinical trials. The aim of this study is to report the prevalence of fibrotic NASH in the general US population across the spectrum of glucose tolerance and evaluate the performance of the recently proposed Fibrotic NASH Index (FNI). Methods: This is a cross-sectional study of US adults participating in the 2017–2020 cycles of the National Health and Nutrition Examination Survey. Participants with available data to calculate FNI (which is based on AST, HbA1c and HDL-cholesterol) and with a reliable vibration controlled transient elastography examination were included. We excluded participants with chronic viral hepatitis, significant alcohol consumption or other forms of liver disease. Probable fibrotic NASH was defined as a Fibroscan-AST (FAST) score ≥ 0.35. Results: We included a total of 6268 participants. The overall prevalence of probable fibrotic NASH was 5.9 % (95 % CI 5.2–6.7) and it increased progressively from participants with normal glucose tolerance (3.7 %, 95 % CI 2–9-4.7) to those with diabetes (14.7 %, 95 % CI 12.1–17.8). The performance of FNI for probable fibrotic NASH was satisfactory in the overall population (area under the receiver operating characteristic curve (AUROC): 0.93, 95 % CI 0.92–0.94) and it maintained a good accuracy also in participants with diabetes (n = 1113, AUROC 0.89, 95 % CI 0.86–0.92). In all groups it outperformed Fibrosis-4. Conclusions: FNI is an easy and reliable test to screen for NASH and its performance is maintained in patients with diabetes, a condition that was shown to negatively influence the performance of several non-invasive scores.

Data are limited on the epidemiology of fibrotic non-alcoholic steatohepatitis (NASH). We applied the recently proposed Fibrotic NASH Index (FNI) to estimate trends in the prevalence of probable fibrotic NASH in the general United States population using data from the 1999–2016 cycles of the National Health and Nutrition Examination Survey. A total of 40 273 participants aged 20 years and older were included in the analysis. The prevalence of probable fibrotic NASH (FNI ≥0.33) in the overall population was 8.4% (95% CI 8.0–8.8), with higher values found in males and in Hispanic participants. It increased from 6.9% (95% CI 6.3–7.6) in 1999–2004 to 9.2% (95% CI 8.4–10.0) in 2011–2016. This positive trend was evident in both sexes and in participants with obesity and diabetes. Finally, it increased progressively with increasing age, body mass index and worse glucose tolerance. NASH prevalence is increasing in the general US population, synchronous with increasing rates of obesity and type 2 diabetes.

Context Laparoscopic sleeve gastrectomy (LSG) is a recognized effective procedure of bariatric surgery, but a poor response in weight loss may still represent a clinical problem. To date there are no validated predictors useful to better perform patient selection. Objective To establish the association of baseline anthropometric, metabolic, and psychologic features with the percent total weight loss (%TWL) and percent excess weight loss (%EWL) 12 months after surgery. Design Retrospective longitudinal analysis of a set of data about obese patients attending the outpatient service of a single obesity center from June 2016 to June 2019. Patients A total of 106 obese patients underwent LSG with presurgery evaluation and follow-up at 12 months after surgery. Main outcome Weight loss 12 months after LSG. Results Patients who achieved a %TWL higher than the observed median (≥34%) were younger, with a lower fasting plasma glucose and glycated hemoglobin, with a lower prevalence of hypertension and with a lower score in the impulsiveness scale, compared with patients with a %TWL Conclusion Metabolic and psychologic features at baseline were independently associated with weight loss and explained a non-negligible effect on the response to LSG. These data suggest that careful metabolic and psychologic profiling could help in sharper indications and personalized pre- and postsurgical follow-up protocols in candidates for LSG.

Objective Few studies investigated the role of different predictors of advanced liver fibrosis in unselected populations. Here, we estimate the prevalence of steatosis and fibrosis in the general United States population by means of transient elastography and evaluate the impact of blood pressure (BP) and diabetes on disease severity. Methods This is a cross-sectional study of United States adults participating in the 2017-2018 cycle of the National Health and Nutrition Examination Survey. Participants underwent a transient elastography examination, and liver steatosis and fibrosis were estimated through the controlled attenuation parameter (CAP) score and liver stiffness measurement (LSM), respectively. Results Four thousand, three hundred and seventy-one participants had reliable transient elastography and BP readings. Steatosis (CAP ≥ 248 dB/m), advanced fibrosis (LSM ≥ 9.6 kPa) and cirrhosis (LSM ≥ 13 kPa) were present in 56.9, 5.5 and 2.9% of participants, respectively. After controlling for potential confounders, risk of steatosis increased proportionally going from participants with optimal (reference) to those with normal [odds ratio (OR) 1.24, 95% confidence interval (CI) 0.83-1.86], high normal (OR 1.41, 95% CI 1.01-1.97) and elevated BP (OR 1.64, 95% CI 1.21-2.21), whereas no significant association was found between BP status and liver fibrosis. Conversely, presence of diabetes increased the risk of both steatosis (OR 2.15, 95% CI 1.49-3.11) and advanced fibrosis (OR 2.25, 95% CI 1.36-3.72). Conclusion Liver steatosis and fibrosis are highly prevalent in the multiethnic United States adult population, raising concerns for future incidence of cirrhosis and its complications. BP status was associated with a progressively higher risk of steatosis, whereas obesity and diabetes were consistently associated with both steatosis and fibrosis.

Aims Liver steatosis, a typical finding in patients with type 2 diabetes (T2D), can lead to cirrhosis and hepatocellular carcinoma. The aim of the present study is to estimate the awareness of liver disease among patients with T2D and whether it differs according to the degree of liver fibrosis estimated by transient elastography (TE). Methods This is a population-based cross-sectional study. We included all patients with T2D that participated in the 2017–2018 cycle of the National Health and Nutrition Examination Survey and underwent a TE examination. Presence of liver steatosis and fibrosis was assessed by the median values of controlled attenuation parameter and liver stiffness measurement, respectively. Results Among the 825 patients included in the analysis, 8.1% (95% CI 5.1%-12.7%) of patients with steatosis were aware of having a liver condition. Even if awareness increased proportionally with increasing severity of organ damage, it remained limited even among patients with advanced fibrosis (17.9%, 95% CI 8.8%-33.3%). Conclusions Despite increasing evidence of a frequent hepatic involvement associated with poor prognosis, awareness of suffering of advanced liver disease in patients with T2D is remarkably low, likely reflecting little recognition also among the team of health care professionals.

Chronic hepatitis C (CHC) and diabetes represent two severe chronic conditions responsible for a considerable number of deaths worldwide. They have a complex, bidirectional relationship. On the one hand, several cohort studies have shown that chronic HCV infection increases both the risk of developing diabetes in non-diabetic subjects (by inducing insulin resistance and promoting β-cell dysfunction) as well as the risk of developing macro and microvascular complications in patients with known diabetes; on the other hand, diabetes is an independent risk factor for liver-related events among patients with CHC, including a higher incidence of hepatocellular carcinoma, liver-related death and transplantation. Importantly, sustained virological response, which can be obtained in the vast majority of patients with the use of direct antiviral agents, does not only lead to a lower rate of liver-related outcomes, but also to improvements of glycemic control and reduction in the rate of complications among patients with diabetes. The aim of this review is to summarize available clinical evidence on the association among CHC, diabetes and related clinical outcomes. We will also briefly discuss the biological mechanisms underpinning the association between CHC and diabetes, as well as the implications this relationship should have on everyday clinical practice.

Recently, an expert panel proposed diagnostic criteria for metabolic dysfunction-associated fatty liver disease (MAFLD) in the pediatric population. The aim of this study was to evaluate the prevalence of MAFLD among US adolescents and to investigate whether the new MAFLD definition is able to identify individuals with more advanced liver disease. We analyzed data from participants 12-18 years old included in the 2017-2020 cycles of the National Health and Nutrition Examination Survey, a large survey aimed at including individuals representative of the non-institutionalized general US population. Participants with a complete vibration-controlled transient elastography exam were included. Steatosis was evaluated through the median controlled attenuation parameter (CAP) and fibrosis through median liver stiffness measurement (LSM). Recently proposed criteria for the diagnosis of MAFLD were applied. Multivariable logistic regression analysis was performed to evaluate the impact of the new MAFLD definition on the odds of significant liver fibrosis. We included a total of 1446 adolescents (mean age: 14.9 years; 52.0% male; 47.3% overweight or obese). No participant reported a previous history of viral hepatitis. Steatosis (CAP ≥ 248 dB/m) was present in 25.9% (95% confidence interval [CI] 23.3-28.9) of individuals, and among these, 87.7% met the MAFLD criteria. Only 22.9% of patients with steatosis had elevated alanine aminotransferase levels. Among participants with steatosis, prevalence of significant liver fibrosis (LSM ≥ 7.4 kPa) did not differ significantly according to whether they met MAFLD criteria (9.7% vs. 15.2%, p = 0.276). In the multivariable model, odds of significant fibrosis did not differ significantly between these two groups. MAFLD criteria are met by most US adolescents with elastographic evidence of steatosis. Nonetheless, these criteria do not appear to improve detection of subjects with more advanced liver disease. Further longitudinal studies are needed to evaluate whether metabolic dysfunction is associated with faster progression toward inflammation, fibrosis, and liver-related events.

Aims Soluble Klotho (s-Klotho) is associated with chronic kidney disease (CKD) and aging, but little is known on its relationship with chronic micro- and macro-vascular complications of type 2 diabetes and glycemic control. Here, we evaluate the association between s-Klotho levels, glycemic control and renal function in patients with type 2 diabetes (T2D). Methods This is a cross-sectional study including 2989 patients with T2D and available s-Klotho measurements from the 2007–2016 cycles of the National Health and Nutrition Examination Survey (mean ± SE, age: 60.0 ± 0.2 years, BMI 33.3 ± 0.2 kg/m2, 46.7 ± 1.3% female). Determination of s-Klotho concentrations was performed with a sandwich ELISA test. Results Patients with higher s-Klotho levels were younger, more frequently female and had a lower prevalence of CKD and higher HbA1c levels. In multivariable linear regression models adjusting for age, race-ethnicity and BMI, both estimated glomerular filtration rate (B = 2.21, 95% CI 1.41–3.01, p p Conclusions s-Klotho levels are dependent on kidney function and glycemic control in patients with T2D. Additional studies elucidating the mechanisms linking glycemic control and s-Klotho levels and exploring their predictive ability of clinically meaningful outcomes in patients with diabetes are needed.

An association between liver stiffness, a surrogate measure of liver fibrosis, and chronic kidney disease (CKD) in patients with nonalcoholic fatty liver disease (NAFLD) has been proposed. However, most studies were small and had low statistical power. We systematically searched PubMed-MEDLINE and Scopus from inception to August 2021 for cross-sectional or cohort studies reporting the association between liver stiffness diagnosed by vibration controlled transient elastography (VCTE) and renal dysfunction. The primary outcome was CKD, defined as a composite of urinary albumin to creatinine ratio (UACR) ≥ 30 mg/g and estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. Measures of association from individual studies were meta-analyzed using random effects models. Of the 526 titles initially scrutinized, 7 cross-sectional studies fulfilled the criteria and were included. For CKD, risk was higher in patients with liver fibrosis assessed by VCTE, compared with patients without (n = 5 studies: OR 2.49, 95% CI 1.89–3.29; test for overall effect z = 6.475, p < 0.001). When increased UACR was considered as an outcome, elevated liver stiffness was associated with a significantly increased risk as well (n = 3 studies: OR 1. 98 95% CI 1.29–3.05; test for overall effect z = 3.113, p = 0.002). Neither analysis showed significant heterogeneity (I2 = 0% and I2 = 46.5%, respectively for the two outcomes). This meta-analysis indicates that elevated liver stiffness is associated with increased odds of kidney outcomes among patients with NAFLD. Wider use of VCTE to screen for advanced fibrosis might help identify patients at risk of end-stage renal disease.

Background Even though hyperglycemia is a well-known cardiovascular risk factor, the absolute risk of cardiovascular events varies to a great extent within each glycemic category. The aim of this study is to evaluate whether N-terminal pro-B natriuretic peptide (NT-ProBNP) could help identify subjects at higher cardiovascular risk, independently of blood glucose levels. Methods Serum NT-ProBNP levels were measured in 5502 people aged 45–79 years without heart failure from the general population (3380 with normoglycemia, 1125 with pre-diabetes and 997 with diabetes) that participated in the 1999–2004 cycles of the National Health and Nutrition Examination Survey. We applied Cox and Fine Gray models adjusted for cardiovascular risk factors to evaluate the association between NT-ProBNP levels and all-cause and cardiovascular mortality through December 2015. Results After a median follow-up of 13 years, 1509 participants died, 330 of cardiovascular causes. In the multivariable-adjusted models, compared with participants with NT-ProBNP Conclusions Elevated NT-ProBNP is independently associated with all-cause and cardiovascular mortality in the general population and could help identify patients at the highest risk. Further studies are needed to evaluate whether intensification of treatment based on biomarker data might lead to improvements in cardiovascular risk reduction.

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.

Purpose Cardiovascular disease (CVD) is the first cause of death in patients with non-alcoholic fatty liver disease (NAFLD) and risk stratification is recommended by current guidelines. The aim of this study is to assess the prevalence of peripheral arterial disease (PAD) in patients with NAFLD and its association with all-cause and cardiovascular disease (CVD) mortality. Methods 9145 participants 40 years or older attended a mobile examination center visit in the 1999–2004 cycles of the National Health and Nutrition Examination Survey. PAD was defined as an ankle-brachial index (ABI) Results The overall prevalence of PAD was 5.9% (95% CI 5.0–6.9). Over a median follow-up of 13 years, 876 participants died, 208 of cardiovascular causes. Incidence rates of all-cause mortality (for 1000 person-years) were 20.2 (95% CI 18.7–21.7) and 70.0 (95% CI 60.1–81.6) for participants without and with PAD, respectively. Multivariable-adjusted Cox proportional hazard models showed that PAD was associated with a higher risk of all-cause (1.8, 95% CI 1.4–2.4) and cardiovascular mortality (HR 2.5, 95% CI 1.5–4.3) after adjustment for potential confounders including prevalent CVD. Conclusion Current guidelines strongly encourage the screening of CVD in patients with NAFLD and the use of the simple and inexpensive measurement of ABI in routine clinical practice may find indication.

Purpose Obesity represents a well-known risk factor for metabolic-dysfunction associated fatty liver disease (MAFLD) and its progression towards cirrhosis. The aim of this study is to estimate the proportion of potential candidates to a bariatric surgery intervention that has an elevated liver stiffness on vibration-controlled transient elastography (VCTE). Materials and Methods This is a cross-sectional study performed using data obtained during the 2017–2018 cycle of the National Health and Nutrition Examination Survey. Potential candidates for a bariatric surgery intervention from the general US population were identified by applying criteria from international guidelines. All included participants were evaluated by VCTE. A controlled attenuation parameter (CAP) value ≥ 288 dB/m was considered indicative of steatosis while liver stiffness measurement (LSM) was considered elevated if ≥ 9.7 kPa. Multivariable logistic regression models were fitted to identify independent predictors of both outcomes. Results A total of 434 participants were included (mean age 42.9 ± 0.6 years; 54.4% women). Among them, 76.7% (95% CI 71.7–81.0) had steatosis, while 23.1% (95% CI 17.8–29.3) had an elevated LSM. Male sex, older age, γ-glutamyltranspeptidase levels, and body mass index (BMI) were independent predictors of steatosis, while BMI was the only independent predictor of elevated LSM. Non-Hispanic black participants were protected from both outcomes, while other ethnicities were not. Conclusion The prevalence of elevated LSM is high in potential candidates for a bariatric surgery intervention. Accurate screening for occult advanced liver disease might be indicated in this patient population. Graphical abstract