Proceedings of the 5th Meeting of Translational Hepatology, organized by the Spanish Association for the Study of the Liver (AEEH).

This is the summary report of the 5th Translational Hepatology Meeting, endorsed by the Spanish Association for the Study of the Liver (AEEH) and held in Seville, Spain, in October 2023. The meeting aimed to provide an update on the latest advances in the field of basic and translational hepatology, covering different molecular, cellular, and pathophysiological aspects of the most relevant clinical challenges in liver pathologies. This includes the identification of novel biomarkers and diagnostic tools, the understanding of the relevance of immune response and inflammation in liver diseases, the characterization of current medical approaches to reverse liver diseases, the incorporation of novel molecular insights through omics techniques, or the characterization of the impact of toxic and metabolic insults, as well as other organ crosstalk, in liver pathophysiology.

Prospective Assessment of Bone Metabolism Biomarkers and Survival in Metastatic Castration-resistant Prostate Cancer Patients Treated with Radium-223: The PRORADIUM Study.

Background: Radium-223 is an active therapy option for bone metastatic castration-resistant prostate cancer (mCRPC). The lack of adequate biomarkers for patient selection and response assessment are major drawbacks for its use.

Objective: To assess the prognostic value of bone metabolism biomarkers (BMBs) in ra-223-treated mCRPC patients.

Mortality Attributable to Environmental Tobacco Smoke Exposure in Spain in 2020.

Introduction And Objectives: Exposure to environmental tobacco smoke (ETS) is associated with increased mortality and morbidity. The objective of this study was to estimate the impact of ETS exposure in Spain on mortality in 2020 in the population aged 35 years and over.

Methods: A method of estimating attributable mortality (AM) based on the prevalence of ETS exposure was applied.

Prevalence of atherogenic dyslipidemia, related factors and level of lipid control in the general population of Galicia. GALIPEMIAS study.

Objectives: GALIPEMIAS is a study designed to establish the prevalence of familial dyslipidemia in the general population of Galicia. The objective of the present study was to assess the prevalence of atherogenic dyslipidemia (AD), its relationship with other cardiovascular risk (CVR) factors, and the degree of lipid control.

Methods: Cross-sectional study carried out in the general population over 18 years of age residing in Galicia and with a health card from the Galician Health Service (N=1,000).

Effectiveness of COVID-19 vaccine booster in the general population and in subjects with comorbidities. A population-based study in Spain.

Background: Research on the effectiveness of COVID-19 booster-based vaccine schedule is ongoing and real-world data on vaccine effectiveness (VE) in comorbid patients are limited. We aimed to estimate booster dose VE against SARS-CoV-2 infection and COVID-19 severity in the general population and in comorbid patients.

Method: A retrospective test-negative control study was undertaken in Galicia-Spain (December 2020-November 2021).

Locoregional relapse after sparing mastectomies and immediate reconstruction in women with breast cancer.

Introduction: In recent years, cultural changes in today's society and improved risk assessment have increased the indication for mastectomies in women with breast cancer. Various studies have confirmed the oncological safety of sparing mastectomies and immediate reconstruction. The objective of this study is to analyze the incidence of locoregional relapses of this procedure and its impact on reconstruction and overall survival.

Hospitalizations due to and with chronic obstructive pulmonary disease in Galicia: 20 years of evolution.

Objective: This work aims to analyze the evolution of COPD-related hospitalizations in Galicia from 1996 to 2018 both as main cause of admission (DUE TO COPD) or when coded in any diagnostic order (WITH COPD), assessing the influence of age, sex, seasonality, and other main causes of the hospitalization.

Methods: An analysis was conducted of administrative healthcare database (CMBD) data on index COPD-related hospitalizations in Galicia from 1996 to 2018. Crude, specific, and standardized rates were calculated for the entire sample and according to age and sex groups.

COVID-19 vaccine effectiveness against hospitalization due to SARS-CoV-2: A test-negative design study based on Severe Acute Respiratory Infection (SARI) sentinel surveillance in Spain.

Background: With the emergence of SARS-CoV-2, influenza surveillance systems in Spain were transformed into a new syndromic sentinel surveillance system. The Acute Respiratory Infection Surveillance System (SiVIRA in Spanish) is based on a sentinel network for acute respiratory infection (ARI) surveillance in primary care and a network of sentinel hospitals for severe ARI (SARI) surveillance in hospitals.

Methods: Using a test-negative design and data from SARI admissions notified to SiVIRA between January 1 and October 3, 2021, we estimated COVID-19 vaccine effectiveness (VE) against hospitalization, by age group, vaccine type, time since vaccination, and SARS-CoV-2 variant.

Cognitive Status and Nutritional Markers in a Sample of Institutionalized Elderly People.

Background: Since many of the risk factors for cognitive decline can be modified by diet, the study of nutrition and its relationships with cognitive status in aging has increased considerably in recent years. However, there are hardly any studies that have assessed cognitive status using a comprehensive set of neuropsychological tests along with measures of functional capacity and mood and that have related it to nutritional status measured from several nutritional parameters that have shown its relationships with cognitive function.

Objective: To test the differences in depressive symptomatology and in several measures of nutritional status between three groups classified according to their cognitive status (CS hereafter).

Association of Cancer Diagnosis and Therapeutic Stage With Mortality in Pediatric Patients With COVID-19, Prospective Multicenter Cohort Study From Latin America.

Background: Children with cancer are at risk of critical disease and mortality from COVID-19 infection. In this study, we describe the clinical characteristics of pediatric patients with cancer and COVID-19 from multiple Latin American centers and risk factors associated with mortality in this population.

Methods: This study is a multicenter, prospective cohort study conducted at 12 hospitals from 6 Latin American countries (Argentina, Bolivia, Colombia, Ecuador, Honduras and Peru) from April to November 2021.

Sapanisertib plus Fulvestrant in Postmenopausal Women with Estrogen Receptor-Positive/HER2-Negative Advanced Breast Cancer after Progression on Aromatase Inhibitor.

Purpose: This phase II study investigated daily or weekly sapanisertib (a selective dual inhibitor of mTOR complexes 1 and 2) in combination with fulvestrant.

Patients And Methods: Postmenopausal women with estrogen receptor-positive (ER+)/HER2-negative (HER2-) advanced or metastatic breast cancer following progression during/after aromatase inhibitor treatment were randomized to receive fulvestrant 500 mg (28-day treatment cycles), fulvestrant plus sapanisertib 4 mg daily, or fulvestrant plus sapanisertib 30 mg weekly, until progressive disease, unacceptable toxicity, consent withdrawal, or study completion.

Results: Among 141 enrolled patients, baseline characteristics were balanced among treatment arms, including prior cyclin-dependent kinase-4/6 (CDK4/6) inhibitor treatment in 33% to 35% of patients.

Latin American Consensus on the Management of Sepsis in Children: Sociedad Latinoamericana de Cuidados Intensivos Pediátricos [Latin American Pediatric Intensive Care Society] (SLACIP) Task Force: Executive Summary.

The aim of this study was to develop evidence-based recommendations for the diagnosis and treatment of sepsis in children in low- and middle-income countries (LMICs), more specifically in Latin America. A panel was formed consisting of 27 experts with experience in the treatment of pediatric sepsis and two methodologists working in Latin American countries. The experts were organized into 10 nominal groups, each coordinated by a member.

Comprehensive NGS Panel Validation for the Identification of Actionable Alterations in Adult Solid Tumors.

The increasing identification of driver oncogenic alterations and progress of targeted therapies addresses the need of comprehensive alternatives to standard molecular methods. The translation into clinical practice of next-generation sequencing (NGS) panels is actually challenged by the compliance of high quality standards for clinical accreditation. Herein, we present the analytical and clinical feasibility study of a hybridization capture-based NGS panel (Action OncoKitDx) for the analysis of somatic mutations, copy number variants (CNVs), fusions, pharmacogenetic SNPs and Microsatellite Instability (MSI) determination in formalin-fixed paraffin-embedded (FFPE) tumor samples.

One-year efficacy and safety of naloxegol on symptoms and quality of life related to opioid-induced constipation in patients with cancer: KYONAL study.

Objectives: Naloxegol is a peripherally acting µ-opioid receptor antagonist (PAMORA) for treatment of opioid-induced constipation (OIC). The main objective was to analyse the long-term efficacy, quality of life (QOL) and safety of naloxegol in patients with cancer in a real-world study.

Methods: This one-year prospective study included patients older than 18 years, with active oncological disease who were under treatment with opioids for pain control and Karnofsky≥50 and OIC with inadequate response to treatment with laxative (s).

Recommendations for the initial management of multisystem inflammatory syndrome temporally related to COVID-19, in children and adolescents.

Multisystem inflammatory syndrome temporally related to COVID-19 in children and adolescents is a clinical presentation of SARS-CoV-2 infection. It shares some features with Kawasaki disease, toxic shock, sepsis, macrophage activation syndrome, and myocarditis. Few publications have addressed its initial management, which is similar to that proposed for septic shock.

Dietary Patterns and Their Association with Body Composition and Cardiometabolic Markers in Children and Adolescents: Genobox Cohort.

Diet is a key factor for obesity development; however, limited data are available on dietary cluster analysis in children with obesity. We aimed to assess the associations between dietary patterns and obesity and several cardiometabolic markers. Anthropometry, bioelectrical impedance, blood pressure and plasma biomarkers of oxidative stress, inflammation and endothelial damage were determined in 674 Caucasian children, aged 5-16, with normal or excess weight.

Serum Phospholipids Fatty Acids and Breast Cancer Risk by Pathological Subtype.

This study evaluates whether serum phospholipids fatty acids (PL-FAs) and markers of their endogenous metabolism are associated with breast cancer (BC) subtypes. EpiGEICAM is a Spanish multicenter matched case-control study. A lifestyle and food frequency questionnaire was completed by 1017 BC cases and healthy women pairs.

Reduced PICU respiratory admissions during COVID-19.

Background: The COVID-19 pandemic reached the Southern Hemisphere in the autumn of 2020, thus coinciding with its expected annual viral respiratory season. The potential impact of national strategies aimed at mitigating COVID-19 during the pandemic on the incidence of other critical viral lower respiratory tract infections (LRTIs) in children is unknown.

Methods: We analysed admission data for LRTIs from 22 paediatric intensive care units (PICUs) in four countries, part of a large international Latin American registry of children with acute respiratory failure (Red Colaborativa Pediátrica de Latinoamérica [LARed Network]).

Phase III Trial of Adjuvant Capecitabine After Standard Neo-/Adjuvant Chemotherapy in Patients With Early Triple-Negative Breast Cancer (GEICAM/2003-11_CIBOMA/2004-01).

Purpose: Operable triple-negative breast cancers (TNBCs) have a higher risk of relapse than non-TNBCs with standard therapy. The GEICAM/2003-11_CIBOMA/2004-01 trial explored extended adjuvant capecitabine after completion of standard chemotherapy in patients with early TNBC.

Patients And Methods: Eligible patients were those with operable, node-positive-or node negative with tumor 1 cm or greater-TNBC, with prior anthracycline- and/or taxane-containing chemotherapy.

Burden of respiratory disease attributable to secondhand smoke exposure at home in children in Spain (2015).

This study aimed to estimate the number of incident cases and hospital admissions attributable to secondhand smoke (SHS) exposure at home for asthma, otitis media (OM), and lower respiratory infections (LRI) in children in Spain. The burden of respiratory disease caused by SHS exposure was estimated in terms of incident cases and hospitalized cases for asthma, OM, and LRI. Estimates were calculated using the population attributable fraction.

Plasma Androgen Receptor and Docetaxel for Metastatic Castration-resistant Prostate Cancer.

Plasma androgen receptor (AR) gain identifies metastatic castration-resistant prostate cancer (mCRPC) patients with worse outcome on abiraterone/enzalutamide, but its relevance in the context of taxane chemotherapy is unknown. We aimed to evaluate whether docetaxel is active regardless of plasma AR and to perform an exploratory analysis to compare docetaxel with abiraterone/enzalutamide. This multi-institutional study was a pooled analysis of AR status, determined by droplet digital polymerase chain reaction, on pretreatment plasma samples.

PROREPAIR-B: A Prospective Cohort Study of the Impact of Germline DNA Repair Mutations on the Outcomes of Patients With Metastatic Castration-Resistant Prostate Cancer.

Purpose: Germline mutations in DNA damage repair (DDR) genes are identified in a significant proportion of patients with metastatic prostate cancer, but the clinical implications of these genes remain unclear. This prospective multicenter cohort study evaluated the prevalence and effect of germline DDR (gDDR) mutations on metastatic castration-resistance prostate cancer (mCRPC) outcomes.

Patients And Methods: Unselected patients were enrolled at diagnosis of mCRPC and were screened for gDDR mutations in 107 genes.