Diagnostic performance of sixteen biomarkers for MASLD: A study in a Mexican cohort.

BACKGROUND AND AIMS: Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD) poses a heightened cardiovascular risk. Identifying efficient biomarkers for early MASLD detection in resource-limited Latin American regions is crucial. We aimed to evaluate the diagnostic efficacy of sixteen biomarkers for MASLD in Mexican individuals. METHODS: In this cross-sectional and analytical study, steatosis was assessed using vibration-controlled transient elastography. MASLD was defined according to international standards. Assessed biomarkers included: Visceral Fat (VF), Waist Circumference (WC), Waist-Height Ratio (WHtr), Waist-Hip Ratio (WHr), Visceral Adiposity Index (VAI), Hepatic Steatosis Index (HSI), Body Mass Index (BMI), Homeostatic Model Assessment (HOMA), Weight-Adjusted-Waist Index (WWI), Lipid Accumulation Product (LAP), Uric Acid-Creatinine Ratio (UACR), Triglyceride-Glucose Index (TyG) and its variants TyG-WC, TyG-HDL, TyG-BMI, TyG-WHtr. RESULTS: 161 participants were included, of which 122 met MASLD criteria (56 % women, age 53.9 years [47.5-64]) and 39 were healthy controls (76 % women, age 52 [45-64]). The AUROCs of the biomarkers for MASLD were: TyG-WC (0.84), LAP (0.84), TyG-BMI (0.82), TyG-WHtr (0.80), WC (0.78), TyG (0.77), WHtr (0.75), BMI (0.76), VF (0.75), HSI (0.75), TyG-HDL (0.75), WHr (0.72), VAI (0.73), UA/CR (0.70), HOMA (0.71), and WWI (0.69). Sex-based differences were observed. After adjusting for sociodemographic variables, the TyG-WC index was the best predictor of MASLD. CONCLUSIONS: In conclusion, our results underscore the potential of several noninvasive biomarkers for MASLD assessment in a Mexican population, highlighting variations in diagnostic efficacy and cut-off values between sexes. After adjusting, TyG-WC was the best MASLD predictor.

Osteocalcin associates with bone mineral density and VDR gene polymorphisms in type 1 and type 2 diabetes.

Objectives: Bone metabolism is impaired in diabetes mellitus (DM). Our objective is to evaluate the association of bone turnover markers (BTM) and vitamin D receptor (VDR) gene polymorphisms with bone mineral density (BMD) in DM type 1 (T1D) and DM type 2 (T2D). Methods: A total of 165 patients (53 T1D and 112 T2D) were enrolled. BMD was measured by dual-energy X-ray absorptiometry (DEXA). Plasma osteocalcin (OC), beta-CrossLaps (ß-CTX) and N-amino terminal propeptide of type I collagen (P1NP) and VDR gene polymorphisms were evaluated. Results: Participants were 53 T1D (41 years [31-48]) and 112 T2D (60 years [51-66]). BMD were not statistically different between the groups. OC (p<0.001) and P1NP levels (p<0.001) were higher in patients with T1D. The areas under the curve for the prediction of bone pathology were 0.732 (p=0.038) for OC in T1D and 0.697 (p=0.007) in T2D. A significant association was found between lower lumbar BMD and the A allele of BsmI (p=0.03), the A allele of ApaI (p=0.04) and the allele C of the Taql (p=0.046). Also, a significant correlation was found with higher OC levels and the G allele of BsmI (p=0.044), C allele of ApaI (p=0.011), T allele of Taql (p=0.006) and with C allele of FokI (p=0.004). Conclusions: The high negative predictive value of the cut-off point for OC suggests that could be useful in excluding the risk suffering bone loss, allowing offering a personalized clinical approach to prevent this pathology.

Symptomatic gallstone disease: Recurrence patterns and risk factors for relapse after first admission, the RELAPSTONE study.

BACKGROUND: Delayed cholecystectomy in patients with symptomatic gallstone disease is associated with recurrence. Limited data on the recurrence patterns and the factors that determine them are available. OBJECTIVE: We aimed to determine the pattern of relapse in each symptomatic gallstone disease (acute pancreatitis, cholecystitis, cholangitis, symptomatic choledocholithiasis, and biliary colic) and determine the associated factors. METHODS: RELAPSTONE was an international multicenter retrospective cohort study. Patients (n = 3016) from 18 tertiary centers who suffered a first episode of symptomatic gallstone disease from 2018 to 2020 and had not undergone cholecystectomy during admission were included. The main outcome was relapse-free survival. Kaplan-Meier curves were used in the bivariate analysis. Multivariable Cox regression models were used to identify prognostic factors associated with relapses. RESULTS: Mean age was 76.6 [IQR: 59.7-84.1], and 51% were male. The median follow-up was 5.3 months [IQR 2.1-12.4]. Relapse-free survival was 0.79 (95% CI: 0.77-0.80) at 3 months, 0.71 (95% CI: 0.69-0.73) at 6 months, and 0.63 (95% CI: 0.61-0.65) at 12 months. In multivariable analysis, older age (HR = 0.57; 95% CI: 0.49-0.66), sphincterotomy (HR = 0.58, 95% CI: 0.49-0.68) and higher leukocyte count (HR = 0.79; 95% CI: 0.70-0.90) were independently associated with lower risk of relapse, whereas higher levels of alanine aminotransferase (HR = 1.22; 95% CI: 1.02-1.46) and multiple cholelithiasis (HR = 1.19, 95% CI: 1.05-1.34) were associated with higher relapse rates. CONCLUSION: The relapse rate is high and different in each symptomatic gallstone disease. Our independent predictors could be useful for prioritizing patients on the waiting list for cholecystectomies.

Incidence of Small Intestinal Bacterial Overgrowth and Symptoms After 7 Days of Proton Pump Inhibitor Use: A Study on Healthy Volunteers.

INTRODUCTION: Proton pump inhibitors (PPIs) are commonly prescribed drugs. Chronic PPI use has recently been associated with the risk for developing small intestinal bacterial overgrowth (SIBO). It is not known whether the short-term prescription of a PPI can trigger SIBO. Therefore, the aim of the present study was to evaluate the incidence of SIBO and gastrointestinal symptoms after 7 days of PPI use. MATERIALS AND METHODS: A prospective, pilot, open-label study was conducted on asymptomatic healthy volunteers. The incidence of SIBO was evaluated at the baseline and after administration of 40 mg of pantoprazole once a day for 7 days, through a glucose breath test. In addition, the presence of gastrointestinal symptoms, the number of bowel movements, and the consistency of stools, according to the Bristol scale, were assessed. RESULTS: Thirty-eight healthy subjects (71.1% women, mean age 25.18 ± 6.5 years) were analyzed. The incidence of SIBO after 7 days of PPI administration was 7.8% (95% CI 1.6-21.3%). The patients that developed SIBO had a greater prevalence of bloating (p = 0.0002) and flatulence (p = 0.004) after 7 days of treatment. CONCLUSIONS: Our study showed that a short-term 7-day PPI course produced SIBO in 7.8% of healthy subjects. Although, inappropriate use of PPIs should be discouraged, but since more than 90% of subjects who received PPIs for one week did not develop SIBO, the advantages of PPI administration seem to outweigh the disadvantages.

Recurrent genetic variants and prioritization of variants of uncertain clinical significance associated with hereditary breast and ovarian cancer in families from the Region of Murcia.

Objectives: Hereditary breast and ovarian cancer (HBOC) follows an autosomal dominant inheritance pattern of cancer susceptibility genes. The risk of developing this disease is primarily associated with germline mutations in the BRCA1 and BRCA2 genes. The advent of massive genetic sequencing technologies has expanded the mutational spectrum of this hereditary syndrome, thereby increasing the number of variants of uncertain clinical significance (VUS) detected by genetic testing. Methods: A prevalence study of HBOC was performed within 2,928 families from the Region of Murcia, in southeastern Spain. Genetic testing enabled the identification of recurrent pathogenic variants and founder mutations, which were mainly related to the BRCA1 and BRCA2 genes. VUS testing was performed using a prioritization algorithm designed by our working group. Results: Variants c.68_69del, c.212+1G>A, and c.5123C>A were detected in 30 % of BRCA1 carriers, whereas exon 2 deletion concurrent with c.3264dupT, c.3455T>G and c.9117G>A variants were found in 30 % of BRCA2 carriers. A total of 16 VUS (15 %) were prioritized. Conclusions: The genotype-phenotype correlation observed in our study is consistent with the scientific literature. Furthermore, the founder effect of c.1918C>T (BRCA1) and c.8251_8254del (ATM) was verified in the Murcian population, whereas exon 2 deletion (BRCA2) was proven to be a Spanish founder mutation. Our algorithm enabled us to prioritize potentially pathogenic VUS that required further testing to determine their clinical significance and potential role in HBOC.

Value of increased soluble suppressor tumorigenicity biomarker 2 (sST2) on admission as an indicator of severity in patients with COVID-19 / Valor del aumento del biomarcador supresor soluble de tumorigenicidad 2 (sST2) al ingreso como indicador de gravedad en pacientes con COVID-19

Background Soluble suppressor of tumorigenicity-2 (sST2) is a biomarker for heart failure and pulmonary injury. We hypothesize that sST2 could help predict severity of SARS-CoV-2 infections. Methods sST2 was analyzed in patients consecutively admitted for SARS-CoV-2 pneumonia. Other prognostic markers were also measured. In-hospital complications were registered, including death, ICU admission, and respiratory support requirements. Results 495 patients were studied (53% male, age: 57.6±17.6). At admission, median sST2 concentrations was 48.5ng/mL [IQR, 30.6–83.1ng/mL] and correlated with male gender, older age, comorbidities, other severity biomarkers, and respiratory support requirements. sST2 levels were higher in patients who died (n=45, 9.1%) (45.6 [28.0, 75.9]ng/mL vs. 144 [82.6, 319] ng/mL, p<0.001) and those admitted to ICU (n=46, 9.3%) (44.7 [27.5, 71.3] ng/mL vs. 125 [69.0, 262]ng/mL, p<0.001). sST2 levels>210ng/mL were a strong predictor of complicated in-hospital courses, with higher risk of death (OR, 39.3, CI95% 15.9, 103) and death/ICU (OR 38.3, CI95% 16.3–97.5) after adjusting for all other risk factors. The addition of sST2 enhanced the predictive capacity of mortality risk models. Conclusions sST2 represents a robust severity predictor in COVID-19 and could be an important tool for identifying at-risk patients who may benefit from closer follow-up and specific therapies (AU)

Antecedentes El supresor soluble de tumorigenicidad 2 (sST2) es un biomarcador de insuficiencia cardiaca y daño pulmonar. Nuestra hipótesis es que la determinación de sST2 al ingreso podría ayudar a predecir la gravedad de la infección por SARS-CoV-2. Métodos Se analizó la concentración de sST2 en pacientes ingresados por neumonía por SARS-CoV-2, junto con otros biomarcadores pronósticos conocidos. Asimismo, se registraron las complicaciones durante la estancia hospitalaria, incluidas la muerte, el ingreso en Unidad de Cuidados Intensivos (UCI) y los requerimientos de soporte respiratorio. Resultados Se estudiaron 495 pacientes (53% hombres, edad 57,6 ± 17,6). Al ingreso, la mediana de la concentración de sST2 fue 48,5 ng/mL (índice intercuartílico [IQR] 30,6-83,1 ng/mL) y correlacionó con el género masculino, una mayor edad, comorbilidades, otros biomarcadores de gravedad, así como necesidad de soporte respiratorio. Los niveles de sST2 fueron mayores en pacientes que fallecieron (n = 45, 9,1%) (45,6 [28,0, 75,9] ng/mL vs. 144 [82,6, 319] ng/mL, p < 0,001) y aquellos que requirieron ingreso en UCI (n = 46, 9,3%) (44,7 [27,5, 71,3] ng/mL vs. 125 [69,0, 262] ng/mL, p < 0,001). Así, los valores de sST2 > 210 ng/mL se han demostrado como un fuerte predictor de complicaciones, con un mayor riesgo de fallecimiento (odds ratio [OR], 39,3, intervalo de confianza [IC] 95% 15,9, 103) y fallecimiento o ingreso en UCI (OR 38,3, IC 95% 16,3-97,5), tras el ajuste por todos los demás factores de riesgo. La adición de la determinación de los niveles de sST2 mejoró la potencia predictiva de los modelos de riesgo desarrollados. Conclusiones El sST2 representa un predictor robusto de la gravedad en pacientes con COVID-19 y podría convertirse en una herramienta importante para la identificación de pacientes en riesgo que podrían beneficiarse de un mayor seguimiento y terapias específicas (AU)

Pancreatic cancer, autoimmune or chronic pancreatitis, beyond tissue diagnosis: Collateral imaging and clinical characteristics may differentiate them.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies and is developing into the 2nd leading cause of cancer-related death. Often, the clinical and radiological presentation of PDAC may be mirrored by other inflammatory pancreatic masses, such as autoimmune pancreatitis (AIP) and mass-forming chronic pancreatitis (MFCP), making its diagnosis challenging. Differentiating AIP and MFCP from PDAC is vital due to significant therapeutic and prognostic implications. Current diagnostic criteria and tools allow the precise differentiation of benign from malignant masses; however, the diagnostic accuracy is imperfect. Major pancreatic resections have been performed in AIP cases under initial suspicion of PDAC after a diagnostic approach failed to provide an accurate diagnosis. It is not unusual that after a thorough diagnostic evaluation, the clinician is confronted with a pancreatic mass with uncertain diagnosis. In those cases, a re-evaluation must be entertained, preferably by an experienced multispecialty team including radiologists, pathologists, gastroenterologists, and surgeons, looking for disease-specific clinical, imaging, and histological hallmarks or collateral evidence that could favor a specific diagnosis. Our aim is to describe current diagnostic limitations that hinder our ability to reach an accurate diagnosis among AIP, PDAC, and MFCP and to highlight those disease-specific clinical, radiological, serological, and histological characteristics that could support the presence of any of these three disorders when facing a pancreatic mass with uncertain diagnosis after an initial diagnostic approach has been unsuccessful.

In Vitro Hemocompatibility and Genotoxicity Evaluation of Dual-Labeled [99mTc]Tc-FITC-Silk Fibroin Nanoparticles for Biomedical Applications.

Nuclear imaging is a highly sensitive and noninvasive imaging technique that has become essential for medical diagnosis. The use of radiolabeled nanomaterials capable of acting as imaging probes has shown rapid development in recent years as a powerful, highly sensitive, and noninvasive tool. In addition, quantitative single-photon emission computed tomography (SPECT) images performed by incorporating radioisotopes into nanoparticles (NPs) might improve the evaluation and the validation of potential clinical treatments. In this work, we present a direct method for [99mTc]Tc-radiolabeling of FITC-tagged silk fibroin nanoparticles (SFN). NPs were characterized by means of dynamic light scattering and scanning electron microscopy. In vitro studies were carried out, including the evaluation of stability in biological media and the evaluation of hemocompatibility and genotoxicity using the cytokinesis block micronucleus (CBMN) assay. The radiolabeling method was reproducible and robust with high radiolabeling efficiency (∼95%) and high stability in biological media. Hydrodynamic properties of the radiolabeled NPs remain stable after dual labeling. The interaction of SFN with blood elicits a mild host response, as expected. Furthermore, CBMN assay did not show genotoxicity induced by [99mTc]Tc-FITC-SFN under the described conditions. In conclusion, a feasible and robust dual-labeling method has been developed whose applicability has been demonstrated in vitro, showing its value for further investigations of silk fibroin NPs biodistribution in vivo.

Value of increased soluble suppressor tumorigenicity biomarker 2 (sST2) on admission as an indicator of severity in patients with COVID-19.

BACKGROUND: Soluble suppressor of tumorigenicity-2 (sST2) is a biomarker for heart failure and pulmonary injury. We hypothesize that sST2 could help predict severity of SARS-CoV-2 infections. METHODS: sST2 was analyzed in patients consecutively admitted for SARS-CoV-2 pneumonia. Other prognostic markers were also measured. In-hospital complications were registered, including death, ICU admission, and respiratory support requirements. RESULTS: 495 patients were studied (53% male, age: 57.6±17.6). At admission, median sST2 concentrations was 48.5ng/mL [IQR, 30.6-83.1ng/mL] and correlated with male gender, older age, comorbidities, other severity biomarkers, and respiratory support requirements. sST2 levels were higher in patients who died (n=45, 9.1%) (45.6 [28.0, 75.9]ng/mL vs. 144 [82.6, 319] ng/mL, p<0.001) and those admitted to ICU (n=46, 9.3%) (44.7 [27.5, 71.3] ng/mL vs. 125 [69.0, 262]ng/mL, p<0.001). sST2 levels>210ng/mL were a strong predictor of complicated in-hospital courses, with higher risk of death (OR, 39.3, CI95% 15.9, 103) and death/ICU (OR 38.3, CI95% 16.3-97.5) after adjusting for all other risk factors. The addition of sST2 enhanced the predictive capacity of mortality risk models. CONCLUSIONS: sST2 represents a robust severity predictor in COVID-19 and could be an important tool for identifying at-risk patients who may benefit from closer follow-up and specific therapies.

Usefulness of PIVKA-II for monitoring after liver transplantation in patients with hepatocellular carcinoma.

The high morbidity and mortality of hepatocellular carcinoma (HCC) has encouraged the search for new biomarkers to be used alongside alpha-foetoprotein (AFP) and imaging tests. The aim of this study was to evaluate the clinical contribution of protein induced by vitamin K absence or antagonist-II (PIVKA-II) for HCC monitoring after liver transplantation (LT) and compare it with AFP, a routinely used tumour marker. A total of 46 HCC patients (Milan criteria) were enrolled in this study. Serum levels of PIVKA-II and AFP were measured before and after transplantation. Clinical features were determined for all the patients that were included. Significant correlations were found between PIVKA-II expression levels and some clinicopathological features, such as tumour size and number of pre-transplant transarterial chemoembolizations (TACEs). Serum levels of PIVKA-II and AFP decreased significantly after LT and increased in patients with tumour recurrence. Serum PIVKA-II levels may play an important role in predicting disease severity. Furthermore, monitoring PIVKA-II levels in HCC transplant recipients reflects the tumor early recurrence after transplantation and could be used, complementing AFP and imaging tests, as a novel biomarker of this pathology.

Comparación de distintas herramientas para la evaluación de la malnutrición y la sarcopenia en pacientes con cirrosis hepática / Comparison of different tools for the evaluation of malnutrition and sarcopenia in patients with liver cirrhosis

Introducción: la malnutrición y la sarcopenia son frecuentes en la población con cirrosis hepática y generan un impacto negativo en el estado funcional y la esperanza de vida de estos pacientes. Existen múltiples herramientas para la valoración de la malnutrición y la sarcopenia en los pacientes con cirrosis hepática. Objetivo: valorar la malnutrición y la sarcopenia en la cirrosis hepática y comparar distintas herramientas diagnósticas aplicables en esta población. Método: se realizó un estudio analítico de corte transversal con muestreo a conveniencia mediante inclusión continua de pacientes con cirrosis hepática en un hospital de tercer nivel durante diciembre de 2018 a mayo de 2019. Se realizó la valoración nutricional con la antropometría del brazo, el índice de masa corporal (IMC) y el algoritmo del Royal Free Hospital Subjetive Global Assessment (RFH-SGA). Para la valoración de la sarcopenia se aplicó la fuerza de agarre de la mano con un dinamómetro. Los resultados se reportaron en medidas de tendencia central expresadas en frecuencia y porcentaje. (AU)

Introduction: malnutrition and sarcopenia are frequent in the population with liver cirrhosis and have a negative impact on the performance status and life expectancy of these patients. There are multiple assessment tools for malnutrition and sarcopenia in cirrhosis. Some of these tools are reproducible and easy to apply, which facilitates their global application for screening malnutrition and sarcopenia. Objective: to assess malnutrition and sarcopenia in liver cirrhosis and to compare the accuracy of diagnostic tools in this population. Method: a cross-sectional analytical study was conducted with convenience sampling by using continuous inclusion of patients with liver cirrhosis in a tertiary care center during December 2018 to May 2019. The nutritional assessment was carried out with arm anthropometry, body mass index (BMI), and the algorithm of the Royal Free Hospital Subjective Global Assessment (RFH-SGA). For the evaluation of sarcopenia, the hand grip strength test with a hand dynamometer was applied. The results were reported in measures of central tendency expressed in frequency and percentage. A Kendall’s Tau-b rank correlation coefficient was performed with non-parametric variables, considering a p < 0.05 as a statistically significant value. (AU)

[Comparison of different tools for the evaluation of malnutrition and sarcopenia in patients with liver cirrhosis]. / Comparación de distintas herramientas para la evaluación de la malnutrición y la sarcopenia en pacientes con cirrosis hepática.

Introduction: Introduction: malnutrition and sarcopenia are frequent in the population with liver cirrhosis and have a negative impact on the performance status and life expectancy of these patients. There are multiple assessment tools for malnutrition and sarcopenia in cirrhosis. Objective: to assess malnutrition and sarcopenia in liver cirrhosis and to compare the accuracy of diagnostic tools in this population. Method: a cross-sectional analytical study was conducted with convenience sampling by using continuous inclusion of patients with liver cirrhosis in a tertiary care center during December 2018 to May 2019. The nutritional assessment was carried out with arm anthropometry, body mass index (BMI), and the algorithm of the Royal Free Hospital Subjective Global Assessment (RFH-SGA). For the evaluation of sarcopenia, the hand grip strength test with a hand dynamometer was applied. The results were reported in measures of central tendency expressed in frequency and percentage. Results: a total of 103 patients were included with a predominance of the male gender (79.6 %) and a mean age of 51 years (± 10). The etiology of liver cirrhosis corresponded more frequently to alcohol consumption (68 %) and most of the patients were Child-Pugh C (57.3 %) with a mean MELD of 21.9 (± 8.9). A mean BMI with dry weight of 25.2 kg/m2 was reported, and with respect to the WHO classification by BMI, 7.8 % were underweight and 59.2 % were malnourished by RFH-SGA. Sarcopenia was present in 88.3 % using the hand grip strength test, for which a mean of 18.99 kg was found. A Kendall's Tau-b rank correlation coefficient was performed between BMI and RFH-SGA, which showed no statistically significant association, as well as between mean arm muscle circumference percentiles and hand grip strength. Conclusions: global assessment in liver cirrhosis should include screening for malnutrition and sarcopenia, for which validated, accessible and safe application tools should be used, such as anthropometric assessment, RFH-SGA, and hand grip strength.

Introducción: Introducción: la malnutrición y la sarcopenia son frecuentes en la población con cirrosis hepática y generan un impacto negativo en el estado funcional y la esperanza de vida de estos pacientes. Existen múltiples herramientas para la valoración de la malnutrición y la sarcopenia en los pacientes con cirrosis hepática. Objetivo: valorar la malnutrición y la sarcopenia en la cirrosis hepática y comparar distintas herramientas diagnósticas aplicables en esta población. Método: se realizó un estudio analítico de corte transversal con muestreo a conveniencia mediante inclusión continua de pacientes con cirrosis hepática en un hospital de tercer nivel durante diciembre de 2018 a mayo de 2019. Se realizó la valoración nutricional con la antropometría del brazo, el índice de masa corporal (IMC) y el algoritmo del Royal Free Hospital Subjetive Global Assessment (RFH-SGA). Para la valoración de la sarcopenia se aplicó la fuerza de agarre de la mano con un dinamómetro. Los resultados se reportaron en medidas de tendencia central expresadas en frecuencia y porcentaje. Resultados: se incluyeron un total de 103 pacientes, predominando el género masculino (79,6 %), con una edad media de 51 años. La etiología más frecuente de la cirrosis hepática fue el consumo de alcohol (68 %), predominando la clase Child-Pugh C (57,3 %) con una media de MELD de 21,9 (± 8,9). Se reportó una media de IMC con peso seco de 25,2 kg/m2 y, respecto a la clasificación de la OMS, un 7,8 % se encontraban en bajo peso y un 59,2 % en malnutrición según la RFH-SGA. Un 88,3 % presentó sarcopenia al utilizar la fuerza de agarre de la mano, cuyo valor medio fue de 18,99 kg. Se realizó una correlación con Tau b de Kendall entre IMC y RFH-SGA sin evidenciarse ninguna asociación significativa, al igual que entre los percentiles de la circunferencia muscular media de brazo (MAMC) y la fuerza de agarre de la mano. Conclusiones: la valoración integral de la cirrosis hepática debe incluir el escrutinio de la malnutrición y la sarcopenia, existiendo herramientas de fácil acceso y aplicación segura validadas en esta población, como la valoración antropométrica, el RFH-SGA y la fuerza de agarre de la mano.

Position statement on the use of albumin in liver cirrhosis.

Cirrhosis is characterised by a prolonged asymptomatic period in which the inflammation persists, increasing as the disease progresses. Characteristic of this is the increase in pro-inflammatory cytokines and pro-oxidant molecules which are determining factors in the development of multiple organ dysfunction. In the early development of cirrhosis, splanchnic arterial vasodilation, activation of vasoconstrictor systems (renin-angiotensin-aldosterone) and the sympathetic nervous system (noradrenaline) bring about bacterial translocation and systemic dissemination via portal circulation of bacterial products, and molecular patterns associated with damage, which exacerbate the systemic inflammation present in the patient with cirrhosis. Albumin is a molecule that undergoes structural and functional changes as liver damage progresses, affecting its antioxidant, immunomodulatory, oncotic and endothelial stabilising properties. Our knowledge of the properties of albumin reveals a molecule with multiple treatment options in patients with cirrhosis, from the compensated then decompensated phases to multiple organ dysfunction. Its recognised uses in spontaneous bacterial peritonitis, post-paracentesis circulatory dysfunction, acute kidney injury and hepatorenal syndrome are fully validated, and a treatment option has opened up in decompensated cirrhosis and in acute-on-chronic liver disease.

CA 15-3 prognostic biomarker in SARS-CoV-2 pneumonia.

The severity of lung involvement is the main prognostic factor in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Carbohydrate antigen 15-3 (CA 15-3), a marker of lung damage and fibrosis, could help predict the prognosis of SARS-CoV-2 pneumonia. This was a retrospective and observational study. CA 15-3 was analyzed in the blood samples of patients consecutively admitted for SARS-CoV-2 pneumonia and whose blood samples were available in the biobank. Other prognostic markers were also measured (interleukin 6 [IL6], C-reactive protein [CRP], D-dimer, troponin T, and NT-ProBNP). The occurrence of in-hospital complications was registered, including death, the need for medical intensive care, and oxygen therapy at discharge. In this study, 539 patients were recruited (54.9% men, mean age: 59.6 ± 16.4 years). At admission, the mean concentrations of CA 15-3 was 20.5 ± 15.8 U/mL, and the concentration was correlated with male sex, older age, and other severity markers of coronavirus disease of 2019 (COVID-19) (IL6, CRP, D-dimer, troponine T, and NT-ProBNP). CA 15-3 levels were higher in patients who died (n = 56, 10.4%) (35.33 ± 30.45 vs. 18.8 ± 12.11, p < 0.001), who required intensive medical support (n = 78, 14.4%; 31.17 ± 27.83 vs. 18.68 ± 11.83; p < 0.001), and who were discharged with supplemental oxygen (n = 64, 13.3%; 22.65 ± 14.41 vs. 18.2 ± 11.7; p = 0.011). Elevated CA 15-3 levels (above 34.5 U/mL) were a strong predictor of a complicated in-hospital course, in terms of a higher risk of death (adjusted odds ratio [OR] 3.74, 95% confidence interval [CI]: 1.22-11.9, p = 0.022) and need for intensive care (adjusted OR 4.56, 95% CI: 1.37-15.8) after adjusting for all other risk factors. The degree of lung damage and fibrosis evaluated in terms of CA 15-3 concentrations may allow early identification of the increased risk of complications in patients with SARS-CoV-2 pneumonia.

Nurse-led and Interdisciplinary Secondary Cardiovascular Prevention Programmes: Spanish Cohort of the EUROACTION Project.

BACKGROUND: Cardiovascular prevention and rehabilitation programmes (CVPRP) are a preventive tool, which can reverse unhealthy behaviours and improve risk factor management. They have been successfully implemented in a variety of settings in patients with coronary heart disease (CHD). OBJECTIVE: The objective of this study is to evaluate an interdisciplinary and nurse-led cardiovascular prevention and rehabilitation programme in patients with coronary heart disease. METHODS: Six pairs of hospitals were randomised between intervention (INT) and usual care (UC) patients. The interdisciplinary team in the intervention hospital carried out a 16-week CVPRP to reach European risk factor goals. The trial is registered as ISRCTN 71715857. RESULTS: The proportion of patients achieving European cardiovascular recommendations in Spain increased in the intervention hospital, mainly regarding fruit and vegetable consumption (INT 98% vs. UC 53%, p<0.001), oily fish consumption (INT 42% vs. UC 19.5%, p<0.001), self-reported physical activity (INT 31% vs. UC 12.4%, p=0.04), blood pressure (INT 69% vs. UC 47.1%) p< 0.05) and LDL concentrations (INT 86.1% vs. UC 67.6%, p=0.04). CONCLUSION: The EUROACTION nurse-led model of CVPR programme has shown that therapeutic goals in cardiovascular disease prevention are affordable and sustainable in everyday clinical practice. EUROACTION model adapted in Spain has produced a healthier lifestyle.

Next step in molecular genetics of hereditary breast/ovarian cancer: Multigene panel testing in clinical actionably genes and prioritization algorithms in the study of variants of uncertain significance.

INTRODUCTION: BRCA1 and BRCA2 are the two main genes causing hereditary breast and ovarian cancer (HBOC). However, thanks to the development of Next Generation Sequencing (NGS), other genes linked to this syndrome (CHEK2, BRIP1, ATM and PALB2 among others) can be analysed. MATERIAL AND METHODS: an analysis by multigene panel testing was performed in 138 index cases (ICs) from HBOC Spanish families with a previous non-informative result for BRCA1/2. The BRCA Hereditary Cancer Master™ Plus kit, including 26 actionable and candidate genes related to HBOC was employed. Once classified, an algorithm was employed to prioritized those variants of unknown significance with a higher risk of having a deleterious effect. Moreover, a mRNA splicing assay was performed for the prioritized VUS c.3402+3A > C in ATM, located at intron 23. RESULTS: A total of 82 variants were found: 70 VUS and 12 pathogenic or probably pathogenic variants. The diagnostic yield in actionable genes non-BRCA was 7.97% of the total tested ICs. Overall, 19 VUS were prioritized, which meant 27% of the 70 total VUS. RNA analysis of the variant 3402+3A > C confirmed a deleterious impact on splicing. DISCUSSION: The implementation of a multigene panel in HBOC studied families improved the diagnostic yield, concordant with results obtained in previous publications. Due to the important number of VUS obtained in NGS, the application of a prioritization algorithm is needed in order to select those variants in which it is necessary to conduct further studies.

The Liver and COVID-19 in Mexico.

Content available: Author Interview and Audio Recording.