Background: Metabolic syndrome (MetS), prediabetes (PreDM) and metabolic-associated fatty liver disease (MAFLD) share pathophysiological pathways concerning type 2 diabetes mellitus (T2DM) onset. The non-invasive assessment of MAFLD combined with PreDM and MetS features might provide further accuracy in predicting hyperglucaemic status with the description of singular clinical phenotypes.Methods: A retrospective cohort study was performed on 2799 patients recruited in the Vascular-Metabolic CUN cohort. The main outcome was the incidence of T2DM according to ADA criteria. MetS and PreDM were defined according to ATP III and ADA criteria, respectively. Hepatic steatosis index (HSI) was used to detect patients with MAFLD.Results: MetS and PreDM were more common in patients with MAFLD (35% vs. 8% and 34% vs. 18%, respectively). MAFLD showed clinical interaction with MetS and PreDM in the prediction of T2DM [MAFLD-MetS interaction HR= 4.48 (3.37-5.97) and MAFLD-PreDM interaction HR = 6.34 (4.67-8.62)]. These findings supported the description of five different liver status-linked phenotypes with increasing risk of T2DM: Metabolically healthy patients (1,5% of T2DM incidence), MAFLD (4,4% of T2DM incidence), MAFLD and MetS (10,6% of T2DM incidence), PreDM (11,1% of T2DM incidence) and MAFLD and PreDM (28,2% of T2DM incidence). These phenotypes provided independent capacity of prediction of T2DM incidence after adjustment for age, sex, tobacco and alcohol consumption, obesity and number of SMet features with a c-Harrell=0.84.Conclusions: MAFLD interplay with MetS and PreDM might help to discriminate patient risk of T2DM in the clinical setting through metabolic remodelling-based phenotypes.

AimsThe association between body mass index (BMI) fluctuation and BMI fluctuation rate with cardiovascular stress morbidities in a Caucasian European cohort was evaluated to ascertain the impact of weight cycling. MethodsA total of 4,312 patients of the Vascular-Metabolic CUN cohort (VMCUN cohort) were examined and followed up during 9.35 years ( +/- 4.39). Cox proportional hazard ratio analyses were performed to assess the risk of developing cardiovascular stress-related diseases (CVDs) across quartiles of BMI fluctuation, measured as the average successive variability (ASV) (ASV = |BMIt0 - BMIt1| + |BMIt1 - BMIt2| + |BMIt2-BMIt3| + horizontal ellipsis + |BMItn - 1 - BMItn|/n - 1), and quartiles of BMI fluctuation rate (ASV/year). ResultsThere were 436 incident cases of CVD-associated events involving 40,323.32 person-years of follow-up. A progressively increased risk of CVD in subjects with greater ASV levels was found. Also, a higher level of ASV/year was significantly associated with an increased risk of developing CVD stress independent of confounding factors with a value of 3.71 (95% CI: 2.71-5.07) for those in the highest quartile and 1.82 (95% CI: 1.33-2.50) for those in the third quartile. ConclusionsThe BMI fluctuation rate seems to be a better predictor than BMI fluctuation of the potential development of cardiovascular stress morbidities. The time-rated weight fluctuations are apparently more determinant in increasing the risk of a CVD than the weight fluctuation itself, which is remarkable in subjects under yo-yo weight patterns for precision medicine.

Introduction: The combination of easy-to-obtain validated biomarkers is interesting in the prognostic evaluation of patients at cardiovascular risk in a precision medicine scenario. The evaluation of the effect modification of insulin resistance and liver fibrosis with the Triglyceride-Glucose index (TyG) and Fibrosis-4 index (FIB4) might provide prognostic information in patients at cardiovascular risk. Patients and methods: A retrospective cohort study was performed with 2055 patients recruited in the Vascular Metabolic CUN cohort. The studied outcome was the incidence rate of major cardiovascular events (MACE). The Systematic Coronary Risk Evaluation (SCORE), FIB4 and TyG indexes were calculated according to validated formulas. Results: FIB4 and TyG showed a synergistic interaction using validated cut-offs for both indexes in the prediction of MACE (Hazard ratio (HR) 1.05 CI95% 1.01-1.08) which remained after adjustment by age, sex, SCORE subgroup, presence of diabetes, or previous MACE using standardized cut-off (HR 2.29 CI95% 1.33-3.94). Finally, a subgroup with significant TyG and FIB4 showed a higher cardiovascular risk in the study population (adjusted HR 3.34 CI 95% 1.94-5.77). Conclusion: The combined interpretation of TyG and FIB4 indexes might have a potential predictive value of major cardiovascular events.

BackgroundDiets high in acid load may contribute to kidney function impairment. This study aimed to investigate the association between dietary acid load and 1-year changes in glomerular filtration rate (eGFR) and urine albumin/creatinine ratio (UACR). MethodsOlder adults with overweight/obesity and metabolic syndrome (mean age 65 +/- 5 years, 48% women) from the PREDIMED-Plus study who had available data on eGFR (n = 5,874) or UACR (n = 3,639) at baseline and after 1 year of follow-up were included in this prospective analysis. Dietary acid load was estimated as potential renal acid load (PRAL) and net endogenous acid production (NEAP) at baseline from a food frequency questionnaire. Linear and logistic regression models were fitted to evaluate the associations between baseline tertiles of dietary acid load and kidney function outcomes. One year-changes in eGFR and UACR were set as the primary outcomes. We secondarily assessed >= 10% eGFR decline or >= 10% UACR increase. ResultsAfter multiple adjustments, individuals in the highest tertile of PRAL or NEAP showed higher one-year changes in eGFR (PRAL, beta: -0.64 ml/min/1.73 m(2); 95% CI: -1.21 to -0.08 and NEAP, beta: -0.56 ml/min/1.73 m(2); 95% CI: -1.13 to 0.01) compared to those in the lowest category. No associations with changes in UACR were found. Participants with higher levels of PRAL and NEAP had significantly higher odds of developing >= 10% eGFR decline (PRAL, OR: 1.28; 95% CI: 1.07-1.54 and NEAP, OR: 1.24; 95% CI: 1.03-1.50) and >= 10 % UACR increase (PRAL, OR: 1.23; 95% CI: 1.04-1.46) compared to individuals with lower dietary acid load. ConclusionsHigher PRAL and NEAP were associated with worse kidney function after 1 year of follow-up as measured by eGFR and UACR markers in an older Spanish population with overweight/obesity and metabolic syndrome.

Purpose of Review Chronic low-grade inflammation may contribute to the onset and progression of communicable and chronic diseases. This review examined the effects and eventual mediation roles of different nutritional factors on inflammation. Recent Findings Potential nutritional compounds influencing inflammation processes include macro and micronutrients, bioactive molecules (polyphenols), specific food components, and culinary ingredients as well as standardized dietary patterns, eating habits, and chrononutrition features. Therefore, research in this field is still required, taking into account critical aspects of heterogeneity including type of population, minimum and maximum intakes and adverse effects, cooking methods, physiopathological status, and times of intervention. Moreover, the integrative analysis of traditional variables (age, sex, metabolic profile, clinical history, body phenotype, habitual dietary intake, physical activity levels, and lifestyle) together with individualized issues (genetic background, epigenetic signatures, microbiota composition, gene expression profiles, and metabolomic fingerprints) may contribute to the knowledge and prescription of more personalized treatments aimed to improving the precision medical management of inflammation as well as the design of anti-inflammatory diets in chronic and communicable diseases.

Background: Immunosuppression increases the risk of malignancy in liver transplant recipients. The potential impact of mycophenolate mofetil monotherapy on this risk has not been studied. Material/Methods: The incidence and risk factors for de novo malignancies of 392 liver transplant recipients with a survival higher than 3 months and a mean follow-up of 8.5 years were studied. Results: De novo malignancies were diagnosed in 126 patients (32.1%) (64 non-melanoma skin cancer and 81 other malignancies). Sixty-nine patients (18.1%) stopped receiving calcineurin inhibitors and were maintained on mycophenolate mofetil monotherapy. The proportion of time on mycophenolate mofetil monotherapy (obtained after dividing the time on monotherapy by the time until diagnosis of neoplasia/last follow-up) was independently associated with a lower risk of de novo malignancy (HR: 0.16, 95% CI: 0.05-0.48; P=0.001), non-melanoma skin cancer (HR: 0.17, 95% CI: 0.03-0.79; P=0.024), and other malignancies (HR: 0.23, 95% CI: 0.07-0.77; P=0.017). Older age and male sex were also associated with a higher risk of malignancy, and transplantation for hepatocellular carcinoma increased the risk of non-melanoma skin cancer. Conclusions: Mycophenolate mofetil monotherapy is associated with a lower risk of cancer in liver transplant recipients compared with maintenance immunosuppression with calcineurin inhibitors.

Perioperative anemia is an important risk factor for cardiac surgery-associated acute kidney injury (CSA-AKI). Nonetheless, the severity of the anemia and the time in the perioperative period in which the hemoglobin level should be considered as a risk factor is conflicting. The present study introduces the concept of perioperative hemoglobin area under the curve (pHb-AUC) as a surrogate marker of the evolution of perioperative hemoglobin concentration. Through a retrospective analysis of prospectively collected data, we assessed this new variable as a risk factor for the development of acute kidney injury after cardiac surgery in 966 adult patients who underwent cardiac surgery with cardiopulmonary bypass, at twenty-three academic hospitals in Spain. Exclusion criteria were patients on renal replacement therapy, who needed a reoperation because of bleeding and/or with missing perioperative hemoglobin or creatinine values. Using a multivariate regression analysis, we found that a pHb-AUC < 19 g/dL was an independent risk factor for CSA-AKI even after adjustment for intraoperative red blood cell transfusion (OR 1.41, p < 0.05). It was also associated with mortality (OR 2.48, p < 0.01) and prolonged hospital length of stay (4.67 +/- 0.99 days, p < 0.001).

Five pharmaceutical strategies are currently approved by the US FDA for the treatment of obesity: orlistat, lorcaserin, liraglutide, phentermine/topiramate, and bupropion/naltrexone. The most effective treatment seems to be the combined administration of phentermine/topiramate followed by lorcaserin and bupropion/naltrexone. In relation to the management of excessive weight, other aspects also need to be considered, including comorbidities accompanying obesity, drug interactions, and the risk of negative collateral effects, as well as individualized treatments based on the genetic make-up. This review aims to provide an overview of the approved anti-obesity drugs and newer molecules that could affect different targets in the central nervous system or peripheral tissues, the molecular mechanisms, emerging dietary treatments and phytogenic compounds, and pharmacogenetic/nutrigenetic approaches for personalized obesity management.

Background Application of illness-severity scores in Intermediate Care Units (ImCU) shows conflicting results. The aim of the study is to design a severity-of-illness score for patients admitted to an ImCU. Methods We performed a retrospective observational study in a single academic medical centre in Pamplona, Spain. Demographics, past medical history, reasons for admission, physiological parameters at admission and during the first 24 hours of ImCU stay, laboratory variables and survival to hospital discharge were recorded. Logistic regression analysis was performed to identify variables for mortality prediction. Results A total of 743 patients were included. The final multivariable model (derivation cohort = 554 patients) contained only 9 variables obtained at admission to the ImCU: previous length of stay 7 days (6 points), health-care related infection (11), metastatic cancer (9), immunosuppressive therapy (6), Glasgow comma scale 12 (10), need of non-invasive ventilation (14), platelets 50000/mcL (9), urea 0.6 g/L (10) and bilirubin 4 mg/dL (9). The ImCU severity score (ImCUSS) is generated by summing the individual point values, and the formula for determining the expected in-hospital mortality risk is: eImCUSS points*0.099 ¿ 4,111 / (1 + eImCUSS points*0.099 ¿ 4,111). The model showed adequate calibration and discrimination. Performance of ImCUSS (validation cohort = 189 patients) was comparable to that of SAPS II and 3. Hosmer-Lemeshow goodness-of-fit C test was ¿2 8.078 (p=0.326) and the area under receiver operating curve 0.802. Conclusions ImCUSS, specially designed for intermediate care, is based on easy to obtain variables at admission to ImCU. Additionally, it shows a notable performance in terms of calibration and mortality discrimination.