Dietary Iron, Anemia Markers, Cognition, and Quality of Life in Older Community-Dwelling Subjects at High Cardiovascular Risk.

Anemia causes hypo-oxygenation in the brain, which could lead to cognitive disorders. We examined dietary iron intake as well as anemia markers (i.e., hemoglobin, hematocrit, mean corpuscular volume) and diabetes coexistence in relation to neuropsychological function and quality of life. In this study, 6117 community-dwelling adults aged 55-75 years (men) and 60-75 years (women) with overweight/obesity and metabolic syndrome were involved. We performed the Mini-Mental State Examination (MMSE), the Trail Making Test parts A and B (TMT-A/B), Semantic Verbal Fluency of animals (VFT-a), Phonological Verbal Fluency of letter P (VFT-p), Digit Span Test (DST), the Clock Drawing Test (CDT), and the Short Form-36 Health Survey (SF36-HRQL test). Dietary iron intake did not influence neuropsychological function or quality of life. However, anemia and lower levels of anemia markers were associated with worse scores in all neurophysiological and SF36-HRQL tests overall, but were especially clear in the MMSE, TMT-B (cognitive flexibility), and the physical component of the SF36-HRQL test. The relationships between anemia and diminished performance in the TMT-A/B and VFT tasks were notably pronounced and statistically significant solely among participants with diabetes. In brief, anemia and reduced levels of anemia markers were linked to inferior cognitive function, worse scores in different domains of executive function, as well as a poorer physical, but not mental, component of quality of life. It was also suggested that the coexistence of diabetes in anemic patients may exacerbate this negative impact on cognition. Nevertheless, dietary iron intake showed no correlation with any of the outcomes. To make conclusive recommendations for clinical practice, our findings need to be thoroughly tested through methodologically rigorous studies that minimize the risk of reverse causality.

Estimation of fatty liver disease clinical role on glucose metabolic remodelling phenotypes and T2DM onset.

INTRODUCTION: Metabolic syndrome (MetS), prediabetes (PreDM) and Fatty Liver Disease (FLD) share pathophysiological pathways concerning type 2 diabetes mellitus (T2DM) onset. The non-invasive assessment of fatty liver combined with PreDM and MetS features screening might provide further accuracy in predicting hyperglycemic status in the clinical setting with the putative description of singular phenotypes. The objective of the study is to evaluate and describe the links of a widely available FLD surrogate -the non-invasive serological biomarker Hepatic Steatosis Index (HSI)- with previously described T2DM risk predictors, such as preDM and MetS in forecasting T2DM onset. PATIENTS AND METHODS: A retrospective ancillary 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) with standardized thresholds was used to discriminate patients with FLD, which was referred as estimated FLD (eFLD). RESULTS: MetS and PreDM were more common in patients with eFLD as compared to those with an HSI < 36 points (35% vs 8% and 34% vs. 18%, respectively). Interestingly, eFLD showed clinical effect modification with MetS and PreDM in the prediction of T2DM [eFLD-MetS interaction HR = 4.48 (3.37-5.97) and eFLD-PreDM interaction HR = 6.34 (4.67-8.62)]. These findings supported the description of 5 different liver status-linked phenotypes with increasing risk of T2DM: Control group (1,5% of T2DM incidence), eFLD patients (4,4% of T2DM incidence), eFLD and MetS patients (10,6% of T2DM incidence), PreDM patients (11,1% of T2DM incidence) and eFLD and PreDM patients (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. CONCLUSION: Estimated Fatty Liver Disease using HSI criteria (eFLD) interplay with MetS features and PreDM might help to discriminate patient risk of T2DM in the clinical setting through the description of independent metabolic risk phenotypes. [Correction added on 15 June 2023, after first online publication: The abstract section was updated in this current version.].

Epidemiology of Herpes Zoster in the pre-vaccination era: establishing the baseline for vaccination programme's impact in Spain.

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.

Machine learning insights concerning inflammatory and liver-related risk comorbidities in non-communicable and viral diseases.

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.

The Role of Nutrition on Meta-inflammation: Insights and Potential Targets in Communicable and Chronic Disease Management.

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.

One-year longitudinal association between changes in dietary choline or betaine intake and cardiometabolic variables in the PREvención con DIeta MEDiterránea-Plus (PREDIMED-Plus) trial.

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.

Diagnostic scores and scales for appraising Nonalcoholic fatty liver disease and omics perspectives for precision medicine.

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.

Hematological- and Immunological-Related Biomarkers to Characterize Patients with COVID-19 from Other Viral Respiratory Diseases.

COVID-19 has overloaded health system worldwide; thus, it demanded a triage method for an efficient and early discrimination of patients with COVID-19. The objective of this research was to perform a model based on commonly requested hematological variables for an early featuring of patients with COVID-19 form other viral pneumonia. This investigation enrolled 951 patients (mean of age 68 and 56% of male) who underwent a PCR test for respiratory viruses between January 2019 and January 2020, and those who underwent a PCR test for detection of SARS-CoV-2 between February 2020 and October 2020. A comparative analysis of the population according to PCR tests and logistic regression model was performed. A total of 10 variables were found for the characterization of COVID-19: age, sex, anemia, immunosuppression, C-reactive protein, chronic obstructive pulmonary disease, cardiorespiratory disease, metastasis, leukocytes and monocytes. The ROC curve revealed a sensitivity and specificity of 75%. A deep analysis showed low levels of leukocytes in COVID-19-positive patients, which could be used as a primary outcome of COVID-19 detection. In conclusion, this investigation found that commonly requested laboratory variables are able to help physicians to distinguish COVID-19 and perform a quick stratification of patients into different prognostic categories.

Interactions of Comorbidity and Five Simple Environmental Unhealthy Habits Concerning Physical and Mental Quality of Life in the Clinical Setting.

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.

Real-World Multicenter Experience of Immunosuppression Minimization Among 661 Liver Transplant Recipients.

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.

Prevention and treatment of complications of selective internal radiation therapy: Expert guidance and systematic review.

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).

Conversion from Calcineurin Inhibitor-Based Immunosuppression to Mycophenolate Mofetil in Monotherapy Reduces Risk of De Novo Malignancies After Liver Transplantation.

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 hemoglobin area under the curve is an independent predictor of renal failure after cardiac surgery. Results from a Spanish multicenter retrospective cohort study.

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).

The neutrophil to lymphocyte and platelet to lymphocyte ratios as biomarkers for lung cancer development.

OBJECTIVES: Elevated neutrophil-to-lymphocyte ratios (NLR) and platelet-to-lymphocyte ratios (PLR) at time of cancer diagnosis have been associated to poor prognosis in various cancers. There is no data on their natural progression before the cancer diagnosis has been established. We aim to evaluate whether or not the annual changes in these ratios could be early indicators of lung cancer development. MATERIALS AND METHODS: Participants recruited into the Pamplona International Early Lung Cancer Action Program (P-IELCAP, n=3061) between 2001 and 2015 were considered. Complete blood counts (CBC) were registered at annual intervals between enrolment and time of diagnosis. Linear regression was used to calculate the mean annual change in NLR and PLR in participants with ≥3CBCs. Changes were expressed relative to baseline values. Lung cancer incidence density and lung cancer risk (Cox regression analysis) were calculated for different NLR and PLR annual thresholds (<0%, ≥0%, ≥1%, ≥2%, ≥4%). Results were compared to a matched group of participants who did not develop lung cancer. RESULTS: After a median follow-up of 80 months and a median of 4 (IQR 3-6) CBCs, subjects who developed lung cancer (n=32) showed greater NLR and PLR annual changes than matched controls (n=103) (2.56% vs. 0.27% [p=0.25] per year; and 3.75% vs. 0.33% [p=0.053] per year, respectively). Lung cancer incidence density per 100 person-years increased with higher annual NLR and PLR thresholds. On multivariable analysis (adjusting for emphysema and baseline lung-function), NLR and PLR were not significant lung cancer predictors. However, among individuals with emphysema, for each relative unit increase in PLR, lung cancer risk increased 5% (p=0.03). There was a significant supra-additive risk effect between PLR increase and emphysema. Annual NLR change was not a significant lung cancer predictor. CONCLUSION: In a lung cancer screening setting, the assessment of annual PLR change could help predict lung cancer development.

The neutrophil-to-lymphocyte ratio as a marker of systemic endothelial dysfunction in asymptomatic subjects. / El índice neutrófilo/linfocito como marcador de disfunción sistémica endotelial en sujetos asintomáticos.

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.

Design and Performance of a New Severity Score for Intermediate Care.

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.