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Background: Precision nutrition is based on the integration of individual's phenotypical and biological characteristics including genetic variants, epigenetic marks, gut microbiota profiles, and metabolite fingerprints as well as medical history, lifestyle practices, and environmental and cultural factors. Thus, nutriomics areas including nutrigenomics, nutrigenetics, nutriepigenetics, nutrimetabolomics, and nutrimetagenomics have emerged to comprehensively understand the complex interactions between nutrients, diet, and the human body's molecular processes through precision nutrition., Summary: This document from the Ibero-American Network of Nutriomics and Precision Nutrition (RINN22; https://rinn22.com/) provides a comprehensive overview of the concepts of precision nutrition approaches to guide their application in clinical and public health as well as establish the position of RINN22 regarding the current and future state of precision nutrition., Key Messages: The progress and participation of nutriomics to precision nutrition is an essential pillar for addressing diet-related diseases and developing innovative managing strategies, which will be promoted by advances in bioinformatics, machine learning, and integrative software, as well as the description of specific novel biomarkers. In this context, synthesizing and critically evaluating the latest developments, potential applications, and future needs in the field of nutrition is necessary with a holistic perspective, incorporating progress in omics technologies aimed at precision nutrition interventions. This approach must address and confront healthy, social, food security, physically active lifestyle, sanitation, and sustainability challenges with preventive, participatory, and predictive strategies of personalized, population, and planetary nutrition for a precision tailored health., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: The diagnosis of pulmonary embolism (PE) is based on the application of a priori probability scales such as the Wells scale or PERC. However, the clinical heterogeneity of this pathology results in the absence of a target population to apply these algorithms. The Wells score does consider the possibility of an alternative diagnosis, awarding an additional point if no other diagnosis is likely, yet the presence of objective alternative diagnoses can still complicate clinical assessment and lead to unnecessary testing or missed diagnoses., Objective: The aim of this study is to evaluate the discrimination capacity of clinical objective factors with a high negative predictive value for PE, compared to PERC in terms of reducing unnecessary testing across different risk strata of the Wells scale., Materials and Methods: This was a single-center retrospective cohort study, including patients who underwent chest CT angiography to rule out PE at a university hospital between 2008 and 2017, considering the presence of PE as the study outcome. The study collected demographic data, comorbidities, and clinical presentation data. The presence of objective criteria for pneumonia, heart failure, exacerbation of COPD, or the use of anticoagulation in non-oncological patients were considered a priori criteria with a high negative predictive value., Results: The analyses were performed on a cohort of 399 patients with an average age of 65 years and 53% females. A total of 139 patients were diagnosed with PE by CT angiography. The presence of factors with a high NPV showed a sensitivity of 100% in low-risk patients according to Wells, with sensitivity dropping below 50% in other populations. The association of these factors in the PERC plus criteria would allow a reduction of up to 34% in CT angiographies in patients with low risk according to the Wells scale., Conclusions: The combination of risk stratification of the Wells scale and PERC plus criteria allows an absolute reduction of 34.3% in the performance of CT angiographies in patients classified as low risk with a sensitivity and a negative predictive value of 100%. The preexistence of an alternative diagnosis does not allow ruling out PE in patients with intermediate or high risk according to the Wells scale.

Purpose of Review: This integrative search aimed to provide a scoping overview of the relationships between the benefits and harms of alcohol drinking with cardiovascular events as associated to body fat mass and fatty liver diseases, as well as offering critical insights for precision nutrition research and personalized medicine implementation concerning cardiovascular risk management associated to ethanol consumption., Recent Findings: Frequent alcohol intake could contribute to a sustained rise in adiposity over time. Body fat distribution patterns (abdominal/gluteus-femoral) and intrahepatic accumulation of lipids have been linked to adverse cardiovascular clinical outcomes depending on ethanol intake. Therefore, there is a need to understand the complex interplay between alcohol consumption, adipose store distribution, metabolic dysfunction-associated steatotic liver disease (MASLD), and cardiovascular events in adult individuals. The current narrative review deals with underconsidered and apparently conflicting benefits concerning the amount of alcohol intake, ranging from abstention to moderation, and highlights the requirements for additional robust methodological studies and trials to interpret undertrained and existing controversies. The conclusion of this review emphasizes the need of newer multifaceted clinical approaches for precision medicine implementation, considering epidemiological strategies and pathophysiological mechanistic. Newer investigations and trials should be derived and performed particularly focusing both on alcohol's objective consequences as putatively mediated by fat deposition, including associated roles in fatty liver disease as well as to differentiate the impact of different levels of alcohol consumption (absence or moderation) concerning cardiovascular risks and accompanying clinical manifestations. Indeed, the threshold for the safe consumption of alcoholic drinks remains to be fully elucidated., (© 2024. The Author(s).)

The prevalence of cardiovascular diseases (CVDs) is a growing global health concern. Recent advances have demonstrated significant reductions in acute cardiovascular events through the management of modifiable cardiovascular risk factors. However, these factors are responsible for about 50% of the global cardiovascular disease burden. Considering that CVDs are one of the top mortality causes worldwide, the concept of residual cardiovascular risk is an important emerging area of study. Different factors have been proposed as sources of residual risk markers, including non-HDL particles characterization, as well as inflammation measured by serum and imaging technics. Among these, metabolic-associated steatotic liver disease (MASLD) remains controversial. Two opposing viewpoints contend: one positing that fatty liver disease merely reflects classical risk factors and thus adds no additional risk and another asserting that fatty liver disease independently impacts cardiovascular disease incidence. To address this dilemma, one hypothetical approach is to identify specific hepatic energy-yielding mechanisms and assess their impact on the cardiovascular system. Ketogenesis, a metabolic intermediate process particularly linked to energy homeostasis during fasting, might help to link these concepts. Ketogenic metabolism has been shown to vary through MASLD progression. Additionally, newer evidence supports the significance of circulating ketone bodies in cardiovascular risk prediction. Furthermore, ketogenic metabolism modification seems to have a therapeutic impact on cardiovascular and endothelial damage. Describing the relationship, if any, between steatotic liver disease and cardiovascular disease development through ketogenesis impairment might help to clarify MASLD's role in cardiovascular risk. Furthermore, this evidence might help to solve the controversy surrounding liver steatosis impact in CVD and might lead to a more accurate risk assessment and therapeutic targets in the pursuit of precision medicine.

Objective: Comirnaty® is an mRNA vaccine against COVID-19 which has been administered to millions of people since the end of 2020. Our aim was to study epidemiological and clinical factors influencing reactogenicity and functional limitation after the first two doses of the vaccine in health care workers (HCWs)., Methods: Prospective post-authorization cohort study to monitor safety and effectiveness of the vaccine., Results: Local side effects were mild and presented both with first and second dose of Comirnaty. Systemic side effects were more frequent after 2nd dose. Nevertheless, previous SARS-CoV-2 infection was associated with systemic effects after the first dose of the vaccine (OR ranging from 2 to 6). No severe adverse effects were reported. According to multivariate analysis, the degree of self-reported functional limitation after the first dose increased with age, female sex, previous COVID-19 contact, previous SARS-CoV-2 infection, and Charlson Comorbidity Index (CCI). After the second dose, the degree of functional limitation observed was lower in those with previous SARS-CoV-2 infection, and it was positively associated to the degree of functional limitation after the first dose., Conclusions: Systemic adverse effects were more frequent after the second dose of Comirnaty. Previous SARS-CoV-2 infection was associated with systemic effects after the first dose. Age, female sex, previous COVID-19, previous isolation due to COVID-19 contact, and CCI showed to be independent predictors of the degree of functional limitation after the 1st dose of Comirnaty®. After the 2nd dose, the degree of functional limitation was lower in those who previously had SARS-CoV-2 infection., (©The Author 2023. Published by Sociedad Española de Quimioterapia. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)(https://creativecommons.org/licenses/by-nc/4.0/).)

Background: Managing the inflammatory response to SARS-Cov-2 could prevent respiratory insufficiency. Cytokine profiles could identify cases at risk of severe disease., Methods: We designed a randomized phase II clinical trial to determine whether the combination of ruxolitinib (5 mg twice a day for 7 days followed by 10 mg BID for 7 days) plus simvastatin (40 mg once a day for 14 days), could reduce the incidence of respiratory insufficiency in COVID-19. 48 cytokines were correlated with clinical outcome., Participants: Patients admitted due to COVID-19 infection with mild disease., Results: Up to 92 were included. Mean age was 64 ± 17, and 28 (30%) were female. 11 (22%) patients in the control arm and 6 (12%) in the experimental arm reached an OSCI grade of 5 or higher (p = 0.29). Unsupervised analysis of cytokines detected two clusters (CL-1 and CL-2). CL-1 presented a higher risk of clinical deterioration vs CL-2 (13 [33%] vs 2 [6%] cases, p = 0.009) and death (5 [11%] vs 0 cases, p = 0.059). Supervised Machine Learning (ML) analysis led to a model that predicted patient deterioration 48h before occurrence with a 85% accuracy., Conclusions: Ruxolitinib plus simvastatin did not impact the outcome of COVID-19. Cytokine profiling identified patients at risk of severe COVID-19 and predicted clinical deterioration., Trial Registration: https://clinicaltrials.gov/, identifier NCT04348695., Competing Interests: JR-M: Advisory boards and Consulting for BMS, Amgen, Novartis. Rainier, Janssen, Pierre-Fabre. Speaker honoraria from Roche, BMS, Novartis, MSD, Janssen, Pfizer, Astra-Zeneca. Travel, accommodations, expenses: Astellas, Novartis, Roche, BMS, Pfizer, MSD, Astra-Zeneca. Corporate-sponsored research: Astra- Zeneca, BMS, Amgen, Roche, Novartis, MSD, Janssen, Pfizer, Astellas, GSK, PharmaMar, lpsen, Tesaro, Abbvie, Aprea Therapeutics, Eisai, Bayer, Merck, IOVANCE, Nektar. JG-D: Advisory boards and Consulting for Janssen, Pierre-Fabre, BMS, Amgen, Novartis. Speaker honoraria from Pfizer, Janssen, Roche, BMS, Novartis, MSD, Astra-Zeneca. Travel, accommodations, expenses: Astellas, Novartis, Astra-Zeneca. Funding for research: Astra- Zeneca, BMS, Amgen, Roche, Novartis, MSD, Janssen, Pfizer, Astellas, GSK, PharmaMar, lpsen, Tesaro, Abbvie, Merck. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Garcia-Donas, Martínez-Urbistondo, Velázquez Kennedy, Villares, Barquin, Dominguez, Rodriguez-Moreno, Caro, Suarez del Villar, Nistal-Villan, Yagüe, Ortiz, Barba, Ruiz-Llorente, Quiralte, Zanin, Rodríguez, Navarro, Berraondo and Madurga.)

BackgroundHerpes zoster (HZ) affects 1 in 3 persons in their lifetime, and the risk of HZ increases with increasing age and the presence of immunocompromising conditions. In Spain, vaccination guidelines were recently updated to include the recommendation of the new recombinant zoster vaccine (RZV) for certain risk groups.AimTo describe the epidemiology of HZ-related hospitalisations in Spain in order to prioritise vaccination recommendations and define a baseline to monitor the effectiveness of vaccination policies.MethodsRetrospective study using the National Health System's Hospital Discharge Records Database, including all HZ-related hospitalisations from 1998 to 2018.ResultsThe 65,401 HZ-related hospitalisations, corresponded to an annual mean hospitalisation rate of 6.75 per 100,000 population. There was an increasing trend of HZ hospitalisations over the study period. This rate was higher in males and older age groups, particularly over 65 years. Comorbidities with higher risk of readmission were leukaemia/lymphoma (RR 2.4; 95% CI: 2.3-2.6) and solid malignant neoplasm (RR 2.2; 95% CI: 2.1-2.4). Comorbidities associated with higher risk of mortality were leukaemia/lymphoma (RR 2.9; 95% CI: 2.7-3.2), solid malignant neoplasm (RR 2.9; 95% CI: 2.7-3.1) and HIV infection (RR 2.2; 95% CI: 1.8-2.7).ConclusionOf all patients hospitalised with HZ, those with greater risk of mortality or readmission belonged to the groups prioritised by the current vaccination recommendations of the Spanish Ministry of Health. Our study provided relevant information on clinical aspects of HZ and established the base for future assessments of vaccination policies.

Background: Choline and betaine intakes have been related to cardiovascular health., Objectives: We aimed to explore the relation between 1-y changes in dietary intake of choline or betaine and 1-y changes in cardiometabolic and renal function traits within the frame of the PREDIMED (PREvención con DIeta MEDiterránea)-Plus trial., Methods: We used baseline and 1-y follow-up data from 5613 participants (48.2% female and 51.8% male; mean ± SD age: 65.01 ± 4.91 y) to assess cardiometabolic traits, and 3367 participants to assess renal function, of the Spanish PREDIMED-Plus trial. Participants met ≥3 criteria of metabolic syndrome and had overweight or obesity [BMI (in kg/m2) ≥27 and ≤40]. These criteria were similar to those of the PREDIMED parent study. Dietary intakes of choline and betaine were estimated from the FFQ., Results: The greatest 1-y increase in dietary choline or betaine intake (quartile 4) was associated with improved serum glucose concentrations (-3.39 and -2.72 mg/dL for choline and betaine, respectively) and HbA1c levels (-0.10% for quartile 4 of either choline or betaine intake increase). Other significant changes associated with the greatest increase in choline or betaine intake were reduced body weight (-2.93 and -2.78 kg, respectively), BMI (-1.05 and -0.99, respectively), waist circumference (-3.37 and -3.26 cm, respectively), total cholesterol (-4.74 and -4.52 mg/dL, respectively), and LDL cholesterol (-4.30 and -4.16 mg/dL, respectively). Urine creatinine was reduced in quartile 4 of 1-y increase in choline or betaine intake (-5.42 and -5.74 mg/dL, respectively)., Conclusions: Increases in dietary choline or betaine intakes were longitudinally related to improvements in cardiometabolic parameters. Markers of renal function were also slightly improved, and they require further investigation.This trial was registered at https://www.isrctn.com/ as ISRCTN89898870., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

The liver is a key organ involved in a wide range of functions, whose damage can lead to chronic liver disease (CLD). CLD accounts for more than two million deaths worldwide, becoming a social and economic burden for most countries. Among the different factors that can cause CLD, alcohol abuse, viruses, drug treatments, and unhealthy dietary patterns top the list. These conditions prompt and perpetuate an inflammatory environment and oxidative stress imbalance that favor the development of hepatic fibrogenesis. High stages of fibrosis can eventually lead to cirrhosis or hepatocellular carcinoma (HCC). Despite the advances achieved in this field, new approaches are needed for the prevention, diagnosis, treatment, and prognosis of CLD. In this context, the scientific com-munity is using machine learning (ML) algorithms to integrate and process vast amounts of data with unprecedented performance. ML techniques allow the integration of anthropometric, genetic, clinical, biochemical, dietary, lifestyle and omics data, giving new insights to tackle CLD and bringing personalized medicine a step closer. This review summarizes the investigations where ML techniques have been applied to study new approaches that could be used in inflammatory-related, hepatitis viruses-induced, and coronavirus disease 2019-induced liver damage and enlighten the factors involved in CLD development., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Purpose of Review: Nonalcoholic fatty liver disease (NAFLD) is a rising epidemic burden affecting around 25% of the global population. Liver biopsy remains the reference for NAFLD. However, the application of several scales and clinical algorithms have been proposed to diagnose NAFLD using prediction questions and blood biomarkers. This review presents a summarized of the currently available and emerging diagnostic biomarkers and scores used to assess NAFLD., Recent Findings: The limitations of liver biopsy have fostered the development of alternative noninvasive strategies, which have been an area of intensive investigation over the past years. Diagnostic scores for NAFLD have shown to be a good alternative for disease diagnosis and prognosis due to a suitable applicability, good inter-laboratory reproducibility and widespread potential availability with reasonable costs., Summary: The growing NAFLD pandemic urges clinicians to seek alternatives for screening, early diagnosis, and follow-up, especially for those with contraindications for liver biopsy. New promising noninvasive biomarkers and techniques have been developed, evaluated and assessed, including diagnostic biomarkers scores. Moreover, multiomics markers panels involving phenotype, genotype, microbiome and clinical characteristics from patients will facilitate the diagnosis, stratification and prognosis of NAFLD patients with precision medicine approaches., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To evaluate the effect of Non-alcoholic fatty liver disease (NAFLD) status in the impact of lifestyle over Health-related quality of life (HRQoL) in patients with metabolic syndrome (MetS)., Methods: Baseline and 1 year follow up data from the PREDIMED-plus cohort (men and women, 55-75 years old with overweight/obesity and MetS) were studied. Adherence to an energy-restricted Mediterranean Diet (er-MeDiet) and Physical Activity (PA) were assessed with a validated screeners. Hepatic steatosis index (HSI) was implemented to evaluate NAFLD while the SF-36 questionnaire provided HRQoL evaluation. Statistical analyses were performed to evaluate the influence of baseline NAFLD on HRQoL as affected by lifestyle during 1 year of follow up., Results: Data from 5205 patients with mean age of 65 years and a 48% of female participants. Adjusted linear multivariate mixed regression models showed that patients with lower probability of NAFLD (HSI < 36 points) were more responsive to er-MeDiet (β 0.64 vs β 0.05 per er-MeDiet adherence point, p< 0.01) and PA (β 0.05 vs β 0.01 per MET-h/week, p = 0.001) than those with high probability for NAFLD in terms Physical SF-36 summary in the 1 year follow up. 10 points of er-MeDiet adherence and 50 MET-h/week were thresholds for a beneficial effect of lifestyle on HRQoL physical domain in patients with lower probability of NAFLD., Conclusion: The evaluation of NAFLD by the HSI index in patients with MetS might identify subjects with different prospective sensitivity to lifestyle changes in terms of physical HRQoL (http://www.isrctn.com/ISRCTN89898870)., Competing Interests: Author JS-S reports grants from CIBEROBN, ISCIII (Spain), during the conduct of the study; non-financial support from Nut and Dried Fruit Foundation, personal fees from Instituto Danone Spain, grants from Nut and Dried Fruit Foundation to this institution, grants from Eroski Distributors and personal fees from Nut and Dried Fruit Foundation, outside the submitted work. Moreover, he gratefully acknowledges the financial support by ICREA under the ICREA Academia program. The author DR declares the funding of the AstraZeneca Young Investigators Award in Category of Obesity and T2D 2017. The author RS-C acknowledges financial support from the Juan de la Cierva Program Training Grants of the Spanish State Research Agency of the Spanish Ministerio de Ciencia e Innovación y Ministerio de Universidades (FJC2018-038168- I). The author ER reports grants, personal fees, non-financial support and other from California Walnut Commission, grants, personal fees, non-financial support and other from Alexion, personal fees, non-financial support and other from Ferrer International, personal fees from Amarin, personal fees, non-financial support and other from Danone, outside the submitted work. The author JL-M reports personal fees and non-financial support from AMGEN, personal fees and non-financial support from SANOFI, personal fees from MSD, personal fees from Laboratorios Dr. Esteve, and personal fees from NOVO-NORDISK, outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Martínez-Urbistondo, San Cristóbal, Villares, Martínez-González, Babio, Corella, del Val, Ordovás, Alonso-Gómez, Wärnberg, Vioque, Romaguera, López-Miranda, Estruch, Tinahones, Lapetra, Serra-Majem, Bueno-Cavanillas, Tur, Marcos, Pintó, Delgado-Rodríguez, Matía-Martín, Vidal, Vázquez, Ros, Bullón Vela, Palau, Masagué, Abete, Moreno-Rodríguez, Candela-García, Konieczna, García-Ríos, Juárez, Martín, Goday, Zulet, Vaquero-Luna, Orea, Megías, Baltasar, Martínez and Daimiel.)

The association between elevated liver enzymes or FIB-4 (fibrosis index 4) and outcome in patients with venous thromboembolism (VTE) has not been evaluated. Data from patients in RIETE (Registro Informatizado Enfermedad TromboEmbólica) were used to assess the association between elevated liver enzymes or FIB-4 levels and the rates of major bleeding or death in apparent liver disease-free patients with acute VTE under anticoagulation therapy. A total of 6206 patients with acute VTE and without liver disease were included. Of them, 92 patients had major bleeding and 168 died under anticoagulation therapy. On multivariable analysis, patients with elevated liver enzymes were at increased mortality risk (HR: 1.58; 95% CI: 1.10-2.28), while those with FIB-4 levels > 2.67 points were at increased risk for major bleeding (HR: 1.69; 95% CI: 1.04-2.74). Evaluation of liver enzymes and FIB-4 index at baseline in liver disease-free patients with VTE may provide additional information on the risk for major bleeding or death during anticoagulation., (© 2021. Società Italiana di Medicina Interna (SIMI).)

The objective of this study was to examine the interactions between comorbidity and five lifestyle single habits concerning different subscales of quality of life (QoL). For the study, 302 patients were consecutively recruited at the internal medicine department of a tertiary teaching hospital. Lifestyle habits, comorbidities and QoL were recorded according to validated questionnaires. Five single unhealthy habits, such as tobacco consumption, dietary intake of ultra-processed pastries, raw nuts or carbonated drinks, sleep time and physical activity patterns were selected according to previously published data. The main outcomes of the study were the scores of the eight subscales of the SF-36 QoL survey. The aggregate of unhealthy habits showed statistically significant association to every category in the SF-36 questionnaire, both in the univariate and the multivariate analysis when adjusting by age, sex and comorbidity. An interaction was found between comorbidity and unhealthy habits in both physical and mental summaries of SF-36. In conclusion, the lifestyle assessment according to five unhealthy habits is associated with a worse QoL. The interaction between comorbidity and unhealthy habits is especially clear in diseased patients due to the interplay between illness and lifestyle in the prediction of QoL.

Objective: To systematically explore genetic polymorphisms associated with the clinical outcomes in SARS-CoV infection in humans., Methods: This comprehensive literature search comprised available English papers published in PubMed/Medline and SCOPUS databases following the PRISMA-P guidelines and PICO/AXIS criteria., Results: Twenty-nine polymorphisms located in 21 genes were identified as associated with SARS-CoV susceptibility/resistance, disease severity, and clinical outcomes predominantly in Asian populations. Thus, genes implicated in key pathophysiological processes such as the mechanisms related to the entry of the virus into the cell and the antiviral immune/inflammatory responses were identified., Conclusions: Although caution must be taken, the results of this systematic review suggest that multiple genetic polymorphisms are associated with SARS-CoV infection features by affecting virus pathogenesis and host immune response, which could have important applications for the study and understanding of genetics in SARS-CoV-2/COVID-19 and for personalized translational clinical practice depending on the population studied and associated environments., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2020 Omar Ramos-Lopez et al.)

Selective internal radiation therapy (or radioembolization) by intra-arterial injection of radioactive yttrium-90-loaded microspheres is increasingly used for the treatment of patients with liver metastases or primary liver cancer. The high-dose beta-radiation penetrates an average of only 2.5 mm from the source, thus limiting its effects to the site of delivery. However, the off-target diversion of yttrium-90 microspheres to tissues other than the tumor may lead to complications. The most prominent of these complications include radiation gastritis and gastrointestinal ulcers, cholecystitis, radiation pneumonitis, and radioembolization-induced liver disease, which may occur despite careful pretreatment planning. Thus, selective internal radiation therapy demands an expert multidisciplinary team approach in order to provide comprehensive care for patients. This review provides recommendations to multidisciplinary teams on the optimal medical processes in order to ensure the safe delivery of selective internal radiation therapy. Based on the best available published evidence and expert opinion, we recommend the most appropriate strategies for the prevention, early diagnosis, and management of potential radiation injury to the liver and to other organs. (Hepatology 2017;66:969-982)., (© 2017 by the American Association for the Study of Liver Diseases.)

BACKGROUND Long-term morbidity and mortality in liver transplant recipients is frequently secondary to immunosuppression toxicity. However, data are scarce regarding immunosuppression minimization in clinical practice. MATERIAL AND METHODS In this cross-sectional, multicenter study, we reviewed the indications of immunosuppression minimization (defined as tacrolimus levels below 5 ng/mL or cyclosporine levels below 50 ng/mL) among 661 liver transplant recipients, as well as associated factors and the effect on renal function. RESULTS Fifty-three percent of the patients received minimized immunosuppression. The median time from transplantation to minimization was 32 months. The most frequent indications were renal insufficiency (49%), cardiovascular risk (19%), de novo malignancy (8%), and cardiovascular disease (7%). The factors associated with minimization were older age at transplantation, longer post-transplant follow-up, pre-transplant diabetes mellitus and renal dysfunction, and the hospital where the patients were being followed. The patients who were minimized because of renal insufficiency had a significant improvement in renal function (decrease of the median serum creatinine level, from 1.50 to 1.34 mg/dL; P=0.004). Renal function significantly improved in patients minimized for other indications, too. In the long term, glomerular filtration rate significantly decreased in non-minimized patients and remained stable in minimized patients. CONCLUSIONS Immunosuppression minimization is frequently undertaken in long-term liver transplant recipients, mainly for renal insufficiency. Substantial variability exists regarding the use of IS minimization among centers.

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 AND 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., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background and Objective: The neutrophil-to-lymphocyte ratio has demonstrated to be a prognostic inflammatory marker in cardiovascular disease. The objective of this study is to evaluate the association between neutrophil-to-lymphocyte ratio and pathologic urinary albumin/creatinine ratio as an early marker of cardiovascular risk and systemic endothelial dysfunction, associated with microvascular disease, in asymptomatic subjects., Materials and Methods: A unicenter cross-sectional study was conducted, including 1816 asymptomatic subjects. Patients with previous cardiovascular disease, those who were treated with ACE inhibitors and/or angiotensin II receptor blockers and patients with albumin/creatinine ratio over 300mg/g were excluded. The outcome of the study was the presence of a pathologic urinary albumin/creatinine ratio., Results: The neutrophil-to-lymphocyte ratio was significantly associated with altered urinary albumin/creatinine ratio in the univariate analysis and after adjustment for other known endothelial and cardiovascular risk factors (age, hypertension, dyslipidaemia, diabetes or altered glomerular filtration rate). Based on the sensitivity and specificity of different neutrophil-to-lymphocyte ratio thresholds, 3 risk groups were created for altered urinary albumin/creatinine ratio: low risk in those with neutrophil-to-lymphocyte ratio < 1.5, intermediate risk in patients between 1.5 and 3, and high risk in those with neutrophil-to-lymphocyte ratio > 3. These groups were found to have a statistically significant and independent prognostic power for altered urinary albumin/creatinine ratio in asymptomatic patients., Conclusions: The neutrophil-to-lymphocyte ratio appears to be a cost-efficient, non-invasive and independent potential marker of systemic endothelial dysfunction in asymptomatic subjects., (Copyright © 2015 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

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: e(ImCUSS points*0.099 - 4,111)/(1 + e(ImCUSS points*0.099 - 4,11)1). 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 χ2 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.