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Introduction and Objectives: : C-reactive protein (CRP) and D-dimer have been shown to be predictors of severity in patients with COVID-19. The FIB-4 and APRI scoring systems are tools calculated using routine laboratory parameters that allow non-invasive evaluation of liver fibrosis. Some studies have demonstrated that the parameters comprising these scores predict mortality in COVID-19. The objective of this study was to determine the role of various liver injury biomarkers in stratifying the severity of hospitalized patients with COVID-19. Materials and Patients: Analytical and retrospective study. Patients with COVID-19 were included, while those with liver disease were excluded. A receiver operating characteristic (ROC) analysis with 95% confidence intervals (CI) was performed to determine the predictive performance of FIB-4, APRI, D-dimer, and CRP in terms of the need for invasive mechanical ventilation (IMV) and mortality. Results: A total of 448 hospitalized patients with COVID-19 were included in the study. 68.2% were male, with a mean age of 56.27 ± 14.7 years. 35.1% had systemic arterial hypertension, 29.2% had diabetes mellitus, 6% had cancer, 5% had chronic obstructive pulmonary disease, and 3.3% had chronic kidney disease. 21.4% required nasal cannula support, 29.4% required mask with reservoir, 35.5% required high-flow oxygen therapy, and 13.1% required IMV. 48% had severe disease, and 28.1% died. ROC analysis with 95% CI revealed that the best predictor of the need for IMV was the FIB-4 index, with an AUC of 0.637 (95% CI 0.545 - 0.732, p= 0.003), followed by APRI with an AUC of 0.596 (95% CI 0.504-0.687, p=0.04). The best predictor of mortality was FIB-4 with an AUC of 0.689 (95% CI 0.620 - 0.785, p=

Introduction and Objectives: It is estimated that 71 million people live with chronic hepatitis C viral infection (HCV). Part of the comorbidities associated with cirrhosis is frailty. Remarkably, diet is highly important in the management of cirrhosis and liver diseases. Therefore, it is necessary to evaluate the quality of the diet in this population. In this context, we evaluated the frailty and quality of the diet in patients with chronic HCV infection with or without cirrhosis, as well as the association between demographic, clinical, and anthropometric variables. Materials and Patients: A cross-sectional study was conducted in the hepatitis clinic of the Civil Hospital of Guadalajara Fray Antonio Alcalde. Each participant was required to complete the Liver Frailty index (LFI) which include hand grip strength, chair stand test and balance test. Additionally, the mini survey was applied to evaluate the quality of food consumption (Mini-ECCA v.2). This questionnaire includes 14 questions, each with 3 or 4 response options on a Likert scale. The outcome yields three classifications: “healthy food intake, habit to be improved, and unhealthy food intake.'' Finally, upper arm anthropometry was performed. P< 0.05 was considered statistically significant. Results: A preliminary sample of 20 patients was assessed. Of them, 60% (n=12) had only chronic HCV infection, 85% (n=17) of LFI were considered pre-fragile, while the rest of the participants were classified as fragile. The quality of the diet, 65% (n=13), was considered “a habit to be improved.” A relationship was found between the quality of the diet and LFI. Likewise, a negative correlation was also found between the mean arm muscle circumference (MAMC) and the LFI score (r=-0.577; p=0.008) as well as MAMC and time in chair supports (r=-0.504;p=0.023). In addition, we found a positive correlation between the MAMC and hand grip strength (r=-0.624; p=0.003). Conclusions: Some degree of frailty was found in the participants, and the quality of the diet was found to be “a habit to be improved” in most of the population sample.

Arrhythmogenic cardiomyopathy (ACM) is a heart muscle disease characterized by prominent "non-ischemic" myocardial scarring predisposing to ventricular electrical instability. Diagnostic criteria for the original phenotype, arrhythmogenic right ventricular cardiomyopathy (ARVC), were first proposed in 1994 and revised in 2010 by an international Task Force (TF). A 2019 International Expert report appraised these previous criteria, finding good accuracy for diagnosis of ARVC but a lack of sensitivity for identification of the expanding phenotypic disease spectrum, which includes left-sided variants, i.e., biventricular (ABVC) and arrhythmogenic left ventricular cardiomyopathy (ALVC). The ARVC phenotype together with these left-sided variants are now more appropriately named ACM. The lack of diagnostic criteria for the left ventricular (LV) phenotype has resulted in clinical under-recognition of ACM patients over the 4 decades since the disease discovery. In 2020, the "Padua criteria" were proposed for both right- and left-sided ACM phenotypes. The presently proposed criteria represent a refinement of the 2020 Padua criteria and have been developed by an expert European TF to improve the diagnosis of ACM with upgraded and internationally recognized criteria. The growing recognition of the diagnostic role of CMR has led to the incorporation of myocardial tissue characterization findings for detection of myocardial scar using the late‑gadolinium enhancement (LGE) technique to more fully characterize right, biventricular and left disease variants, whether genetic or acquired (phenocopies), and to exclude other "non-scarring" myocardial disease. The "ring-like' pattern of myocardial LGE/scar is now a recognized diagnostic hallmark of ALVC. Additional diagnostic criteria regarding LV depolarization and repolarization ECG abnormalities and ventricular arrhythmias of LV origin are also provided. These proposed upgrading of diagnostic criteria represents a working framework to improve management of ACM patients., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Exercise echocardiography (ExE) may assess left ventricular (LV) systolic and diastolic function, LV outflow tract (LVOT) obstruction, and mitral regurgitation (MR). We aimed to evaluate the prognostic value of these assessments during exercise in patients with hypertrophic cardiomyopathy (HCM)., Methods: LV systolic function, LV-derived filling pressures, LVOT gradients, and MR were prospectively evaluated during treadmill ExE in 285 patients with HCM and preserved LV ejection fraction (EF) (≥50%). Recordings were obtained at rest and peak exercise for LV systolic function and at rest and post-exercise for LVOT gradients, MR, and ratio of early LV inflow velocity to early tissue Doppler annulus velocity (E/e´)., Results: Thirty-seven patients (13%) had LVOT obstruction at rest, and 76 (27%) developed exercise-induced LVOT obstruction. New wall motion abnormalities were detected in 38 patients (13%). E/e´>14 was observed in 129 patients at rest (45%) and in 134 at post-exercise (47%). Corresponding figures for significant MR (moderate or severe) were 21 (7%) and 17 (6%). During follow-up (3.9 ± 2.5 years), 27 patients had a hard event, 39 a combined event (hard plus new atrial fibrillation or syncope), and 58 a combined event or intervention. Exercise electrocardiographic testing, exercise LVEF, and the combination of positive ExE and increased E/e´ with exercise predicted outcome. The worst event rate corresponded to patients with raised E/e' values at post-exercise and positive ExE (annualized hard event-rate of 5.9%)., Conclusions: A comprehensive assessment during ExE is feasible for patients with HCM and preserved LV systolic function, and provides significant incremental prognostic information., Competing Interests: Declaration of competing Interest There is no conflict of interest to disclose., (Copyright © 2020. Published by Elsevier Ltd.)

Introduction and Objectives: Up to 50% of patients with hypertrophic cardiomyopathy (HCM) show no disease-causing variants in genetic studies. Mutations in CSRP3 have been associated with HCM, but evidence supporting pathogenicity is inconclusive. In this study, we describe an HCM cohort with a missense variant in CSRP3 (p.Cys150Tyr) with supporting evidence for pathogenicity and a description of the associated phenotype., Methods: CSRP3 was sequenced in 6456 index cases with a diagnosis of HCM and in 5012 probands with other cardiomyopathies. In addition, 3372 index cases with hereditary cardiovascular disorders other than cardiomyopathies (mainly channelopathies and aortopathies) were used as controls., Results: The p.(Cys150Tyr) variant was identified in 11 unrelated individuals of the 6456 HCM probands, and it was not identified in patients with other cardiomyopathies (p < 0.0001) or in our control population (p < 0.0001). Ten of the index cases were heterozygous and one was homozygous. Homozygous had a more severe phenotype. Family screening identified 17 other carriers. Wild-type individuals showed no signs of disease. The mean age at diagnosis of affected individuals was 55 ± 13 years, and the mean left ventricular wall thickness was 18 ± 3 mm. The variant showed highly age-dependent penetrance. After a mean follow-up of 11 (±8) years, no adverse events were reported in any of the HCM patients., Conclusions: The p.(Cys150Tyr) variant in CSRP3 causes late-onset and low risk form of hypertrophic cardiomyopathy in heterozygous carriers., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background: Filamin C is a cytoskeletal protein expressed in cardiac cells. Nonsense variations in the filamin C gene (FLNC) were associated with dilated and arrhythmogenic cardiomyopathies., Methods and Results: We identified an intronic variation in FLNC gene (c.3791-1G > C) in three unrelated Ashkenazi Jewish families with variable expression of arrhythmia and cardiomyopathy. cDNA was prepared from a mutation carrier's cultured skin fibroblasts. Quantitative PCR demonstrated a reduction in total FLNC transcript, and no other FLNC splice variants were found. Single-nucleotide polymorphism (SNP) analysis revealed heterozygous variations in the genomic DNA that were not expressed in the messenger RNA. Immunohistochemical analysis of cardiac sections detected a normal distribution of filamin C protein in the heart ventricles., Conclusion: The transcript that included the FLNC variant was degraded. Haploinsufficiency in filamin C underlies arrhythmogenic cardiomyopathy with variable symptoms., Competing Interests: Declaration of competing interest None for all authors., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction and Objectives: TTN gene truncating variants (TTNtv) are a frequent cause of dilated cardiomyopathy (DCM). However, there are discrepant data on the associated prognosis. Our objectives were to describe the prevalence of TTNtv in our cohort and to compare the clinical course with that described in the literature., Methods: We included patients with DCM and genetic testing performed using next-generation sequencing. Through a systematic literature research, we collected information about carriers and affected relatives with TTNtv. We compared the cumulative percentage of affected carriers and the survival free of cardiovascular death., Results: One hundred and ten DCM patients were evaluated. A total of 13 TTNtv distributed in 14 probands were identified (12.7%). We found a 21.4% prevalence in familial cases. No significant differences in the relation between age and clinical disease expression were identified. Survival free of cardiovascular death curves constructed from data in the literature seems not to overestimate the risk in our population., Conclusions: The identification of TTNtv in patients with DCM is frequent and provides relevant information about the disease prognosis. The risk of cardiovascular death should not be underestimated. Age related penetrance need to be considered in the familial evaluation., Competing Interests: Declaration of competing interest Drs Juan Pablo Ochoa, Marcos Cicerchia, Joel Salazar-Mendiguchia, Arsonval Lamounier, Diego Garcia-Giustiniani, Xusto Fernandez, Martin Ortiz-Genga are employees of Health in Code SL. Lorenzo Monserrat is CEO of Health in Code SL., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Stress echo (SE) may have a role in the outcome in patients with hypertrophic cardiomyopathy (HCM)., Objectives: The aim was to assess the prognostic value of SE in a retrospective multicenter study in HCM., Methods: We enrolled 706 HCM patients. The employed stress was exercise (n=608) and/or vasodilator (n=146, dipyridamole in 98 and adenosine in 48). We defined SE positivity according to clinical/hemodynamic criteria including: symptoms (all stress modalities), exercise-induced hypotension (failure to increase or fall >20mmHg, exercise) and exercise-induced left ventricular outflow tract obstruction (left ventricular outflow tract obstruction >50mmHg); and ischemic criteria, such as new wall motion abnormalities (new wall motion abnormality) and/or reduction of coronary flow reserve velocity (CFVR≤2.0) on left anterior descending coronary artery with vasodilator stress assessed in 116 patients. All patients completed the clinical follow-up., Results: Positive SE showed more frequently CFVR reduction, exercise-induced hypotension, left ventricular outflow tract obstruction, and symptoms (38, 23, 20 and 15% respectively), but new wall motion abnormality only in 6%. During a median follow-up of 49months 180 events were observed, including 40 deaths. Clinical/hemodynamic criteria did not predict outcome (X2 0.599, p=0.598), whereas ischemia-related SE criteria (X2: 111.120, p<0.0001) was significantly related to outcome. Similarly, mortality was predicted with SE ischemic-criteria (X2 16.645, p<0.0001)., Conclusions: SE has an important prognostic significance in HCM patients, with ischemia-related end-points showing greater predictive accuracy than hemodynamic endpoints. New wall motion abnormalities and impairment of CFVR should be specifically included in SE protocols for HCM., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Dilated cardiomyopathy (DCM) is the most frequent cause of heart transplantation (HTx). The genetic basis of DCM among patients undergoing HTx has been poorly characterized. We sought to determine the genetic basis of familial DCM HTx and to establish the yield of modern next generation sequencing (NGS) technologies in this setting., Methods: Fifty-two heart-transplanted patients due to familial DCM underwent NGS genetic evaluation with a panel of 126 genes related to cardiac conditions (59 associated with DCM). Genetic variants were initially classified as pathogenic mutations or as variants of uncertain significance (VUS). Final pathogenicity status was determined by familial cosegregation studies., Results: Initially, 24 pathogenic mutations were found in 21 patients (40%); 25 patients (48%) carried 19 VUS and 6 (12%) did not show any genetic variant. Familial evaluation of 220 relatives from 36 of the 46 families with genetic variants confirmed pathogenicity in 14 patients and allowed reclassification of VUS as pathogenic in 17 patients, and as non-pathogenic in 3 cases. At the end of the study, the DCM-causing mutation was identified in 38 patients (73%) and 5 patients (10%) harbored only VUS. No genetic variants were identified in 9 cases (17%)., Conclusions: The genetic spectrum of familial DCM patients undergoing HTx is heterogeneous and involves multiple genes. NGS technology plus detailed familial studies allow identification of causative mutations in the vast majority of familial DCM cases. Detailed familial studies remain critical to determine the pathogenicity of underlying genetic defects in a substantial number of cases., (Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: We identified 2 compound heterozygous mutations (p.D1690N and p.G1748D) in the SCN5A gene encoding cardiac Na(+) channels (Nav1.5) in a proband diagnosed with Brugada syndrome type 1. Furthermore, in the allele encoding the p.D1690N mutation, the p.H558R polymorphism was also detected., Objective: The purpose of this study was to analyze the functional properties of the mutated channels as well as the putative modulator effects produced by the presence of the polymorphism., Methods: Wild-type and mutated human Nav1.5 channels were expressed in Chinese hamster ovary cells and recorded using whole-cell patch-clamp technique., Results: Separately, both p.D1690N and p.G1748D mutations produced a marked reduction in peak Na(+) current density (>80%), mainly due to their limited trafficking toward the membrane. Furthermore, p.G1748D mutation profoundly affected channel gating. Both p.D1690N and p.G1748D produced a marked dominant negative effect when cotransfected with either wild-type or p.H558R channels. Conversely, p.H558R was able to rescue defective trafficking of p.D1690N channels toward the membrane when both polymorphism and mutation were in the same construct. Surprisingly, cotransfection with p.D1690N, either alone or together with the polymorphism (p.H558R-D1690N), completely restored the profound gating defects exhibited by p.G1748D channels but only slightly rescued their trafficking., Conclusions: Our results add further support to the hypothesis that Nav1.5 subunits interact among them before trafficking toward the membrane and suggest that a missense mutation can "rescue" the defective gating produced by another missense mutation., (Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Seven- to 10-month-old calves are the typical production of Galician Blond (GB), the most important bovine local beef breed in Spain. As meat lipid repercussions on human health depend on their fatty acid (FA) profile, this study aimed at analysing the individual FA at weaning and at the end of the feeding finishing period, especially trans and cis 18:1 isomers in total lipids of the Longissimus thoracis muscle in GB male calves. Distribution of main FA in veal lipids was characterized by gas-liquid chromatography (GLC) analysis on a high polar glass capillary column. Total trans and cis 18:1 isomers were purified, from total FA (TFA) methyl esters, by preparative reversed-phase high-performance liquid chromatography, to allow subsequent specific analysis of their different isomers by GLC. Calves stayed with their mothers at pasture for 2 or 5 months in intensive or semi-extensive systems, followed by an indoor feeding period. The weaned (W) group was finished on concentrate and hay, whereas the non-weaned (NW) group was finished on concentrate and hay and it continued suckling until slaughter. The studied effects did not present interactions. The duration of the indoor finishing period hardly had a significant influence on the parameters analysed. Compared to W calves, NW calves had higher proportions (% TFA) of 18:3n-3 (+38%, P < 0.0001), 20:5n-3 (+22%, P = 0.005), 22:5n-3 (+13%, P = 0.042), cis monounsaturated FA (MUFA; +8%, P = 0.032), total MUFA (+8%, P = 0.013), n-3 polyunsaturated FA (PUFA; +25%, P = 0.0001) and conjugated linoleic acid (CLA; +48%, P < 0.0001) to the detriment of 18:0 (-10%, P = 0.002), 18:2n-6 (-25%, P = 0.004) and n-6 PUFA (-20%, P = 0.011). With regard to cis and trans 18:1 isomers, NW calves had higher proportions (% total cis or trans 18:1) of Δ11trans and Δ16trans (+25% and +22%, respectively, P < 0.01) and Δ13 + 14trans (+13%, P < 0.05) and lower proportions of Δ6 to 8 and Δ10trans (-28% and 58%, respectively, P < 0.001). NW calves' meat might be more suitable for human health than W calves' meat due to the increase of anti-atherogenous FA such as n-3 PUFA, CLA and 18:1 Δ11trans.

The effect of weaning calves at different ages (NW=not weaned, W5=5.5 months old and W2=weaned after being born and then fed with natural Holstein Friesian milk until 2 months old), on animal performance and carcass and Longissimus thoracis muscle quality, was studied in 36 eight month-old Rubia Gallega calves. Feed ingestions, weight gains, slaughter (SW) and carcass weights (CW), carcass conformation and fat scores, and meat characteristics (24 hours postmortem): colour, pH, water holding capacity, chemical composition and texture (Warner Bratzler (WB) test, sensory panel), were studied. NW calves showed the highest SW and CW (P<0.001). Yellowness (b*), redness (a*) and chroma (C*) were higher in NW than W2 calves (P<0.05). Shear firmness was higher in W2 than in NW and W5 veal. W2 veal was less elastic (P<0.05), tender (P<0.05) and juicy (P<0.01) than NW and W5 veal., (Copyright © 2010 The American Meat Science Association. Published by Elsevier Ltd. All rights reserved.)

Background: The diagnosis of arrhythmogenic right ventricular cardiomyopathy can be challenging. Disease-causing mutations in desmosomal genes have been identified. A novel diagnostic feature, loss of immunoreactivity for plakoglobin from the intercalated disks, recently was proposed., Objective: The purpose of this study was to identify two novel mutations in the intracellular cadherin segment of desmoglein-2 (G812S and C813R in exon 15). Co-segregation of the G812S mutation with disease expression was established in a large Caucasian family. Endomyocardial biopsies of two individuals showed reduced plakoglobin signal at the intercalated disk., Methods: To understand the pathologic changes occurring in the diseased myocardium, functional studies on three mutations in exon 15 of desmoglein-2 (G812C, G812S, C813R) were performed., Results: Localization studies failed to detect any differences in targeting or stability of the mutant proteins, suggesting that they act via a dominant negative mechanism. Binding assays were performed to probe for altered binding affinities toward other desmosomal proteins, such as plakoglobin and plakophilin-2. Although no differences were observed for the mutated proteins in comparison to wild-type desmoglein-2, binding to plakophilin-2 depended on the expression system (i.e., bacterial vs mammalian protein expression). In addition, abnormal migration of the C813R mutant protein was observed in gel electrophoresis., Conclusion: Loss of plakoglobin immunoreactivity from the intercalated disks appears to be the endpoint of complex pathologic changes, and our functional data suggest that yet unknown posttranslational modifications of desmoglein-2 might be involved., (Copyright © 2010 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

The effect of weaning at different ages (NW=not weaned, W5=5.5 months and W2=2 months) on fatty acids (FA) of the Longissimus thoracis (LT) muscle was studied in 36 Galician Blond (GB) calves. Total FA (TFA) were determined by gas chromatography (GC) and 18:1 isomers by a combination of reversed-phase high performance liquid chromatography (HPLC) and GC. NW group showed higher (P<0.001) values of n-3 polyunsaturated FA (PUFA), conjugated linoleic acid (CLA) and 18:1 trans-11 compared to LT from W5 and W2 calves. W2 calves showed the highest levels of n-6 PUFA (P<0.01), 18:1 trans-10 and 18:1 trans-6/7/8 (P<0.001). Generally, W5 calves had intermediate values for TFA and 18:1 isomers. As the suckling period was longer, GB milk and veal FA profiles became more similar, it seems that muscle FA were partially transmitted by the milk FA intake due to the persistence of the reticular grove closing reflex., (Copyright (c) 2010 The American Meat Science Association. Published by Elsevier Ltd.. All rights reserved.)

Fabry disease, an X-linked lysosomal storage disorder affecting both men and women, is a relatively prevalent cause of hypertrophic cardiomyopathy (HCM) and is associated with significant morbidity and early death due to heart failure or ventricular arrhythmias. Fabry cardiomyopathy results from progressive build-up of glycosphingolipids in cardiac structures, but the underlying complex pathophysiologic mechanisms remain poorly understood. Disease-specific enzyme replacement therapy (ERT) is available for Fabry disease and, therefore, attention should be focused on early diagnosis of this progressive, life-threatening disease. Selected cardiology patients at high risk for Fabry disease can be tested using simple enzymatic assays, and diagnosis is confirmed by demonstration of a Fabry mutation. Testing cardiology patients with HCM of unknown etiology may identify previously unrecognized Fabry patients and allow genetic mapping to be carried out to identify other affected family members at a relatively early stage of the disease. Timely intervention early on in the disease is a key, as the best responses to ERT are seen in patients with the lowest degree of cardiac hypertrophy and fibrosis at the start of treatment., (Crown Copyright (c) 2009. Published by Elsevier Ireland Ltd. All rights reserved.)

Seven to nine months old calves are the typical production of Rubia Gallega, which is the most important beef breed in Spain. A study about the influence of weaning status and vacuum storage time on veal quality characteristics is needed. The muscle longissimus thoracis from 22 non-weaned (NW) and 21 weaned (W) calves at 1day post-slaughter, and vacuum packaged for 7 and 14 days were analysed. NW showed higher yellowness and hue values than W but lower pigment concentration. The differences disappeared at longer storage times. The redness, yellowness, hue and chroma increased with aging, but the pigment concentration, expressible juice and toughness decreased with aging. Principal component analysis showed that colour variables were the most determinant characteristics in quality variation. The canonical discriminant analysis separated the samples in three groups: 1 day post-slaughter W, 1day post-slaughter NW, and vacuum packaged W and NW.