Serological response and breakthrough infection after COVID-19 vaccination in patients with cirrhosis and post-liver transplant

BACKGROUND: Vaccine hesitancy and lack of access remain major issues in disseminating COVID-19 vaccination to liver patients globally. Factors predicting poor response to vaccination and risk of breakthrough infection are important data to target booster vaccine programs. The primary aim of the current study was to measure humoral responses to 2 doses of COVID-19 vaccine. Secondary aims included the determination of factors predicting breakthrough infection. METHODS: COVID-19 vaccination and Biomarkers in cirrhosis And post-Liver Transplantation is a prospective, multicenter, observational case-control study. Participants were recruited at 4-10 weeks following first and second vaccine doses in cirrhosis [n = 325; 94% messenger RNA (mRNA) and 6% viral vaccine], autoimmune liver disease (AILD) (n = 120; 77% mRNA and 23% viral vaccine), post-liver transplant (LT) (n = 146; 96% mRNA and 3% viral vaccine), and healthy controls (n = 51; 72% mRNA, 24% viral and 4% heterologous combination). Serological end points were measured, and data regarding breakthrough SARS-CoV-2 infection were collected. RESULTS: After adjusting by age, sex, and time of sample collection, anti-Spike IgG levels were the lowest in post-LT patients compared to cirrhosis (p < 0.0001), AILD (p < 0.0001), and control (p = 0.002). Factors predicting reduced responses included older age, Child-Turcotte-Pugh B/C, and elevated IL-6 in cirrhosis; non-mRNA vaccine in AILD; and coronary artery disease, use of mycophenolate and dysregulated B-call activating factor, and lymphotoxin-α levels in LT. Incident infection occurred in 6.6%, 10.6%, 7.4%, and 15.6% of cirrhosis, AILD, post-LT, and control, respectively. The only independent factor predicting infection in cirrhosis was low albumin level. CONCLUSIONS: LT patients present the lowest response to the SARS-CoV-2 vaccine. In cirrhosis, the reduced response is associated with older age, stage of liver disease and systemic inflammation, and breakthrough infection with low albumin level

Serum miR-181b-5p predicts ascites onset in patients with compensated cirrhosis

Altres ajuts: Ministerio de Ciencia e Innovación; Fondo Europeo de Desarrollo Regional (FEDER); Gilead Sciences (GLD19/00045).Background & Aims: Treatment with non-selective beta-blockers (NSBBs) reduces the risk of ascites, which is the most common decompensating event in cirrhosis. This study aimed to assess the ability of a serum microRNA (miRNA) signature to predict ascites formation and the hemodynamic response to NSBBs in compensated cirrhosis. Methods: Serum levels of miR-452-5p, miR-429, miR-885-5p, miR-181b-5p, and miR-122-5p were analyzed in patients with compensated cirrhosis (N = 105). Hepatic venous pressure gradient (HVPG) was measured at baseline, after intravenous propranolol, and 1 year after randomization to NSBBs (n = 52) or placebo (n = 53) (PREDESCI trial). miRNAs were analyzed at baseline and at 1 year. Results: Nineteen patients (18%) developed ascites, of whom 17 developed ascites after 1 year. miR-181b-5p levels at 1 year, but not at baseline, were higher in patients that developed ascites. The AUC of miR-181b-5p at 1 year to predict ascites was 0.7 (95% CI 0.59-0.78). miR-429 levels were lower at baseline in acute HVPG responders to NSBBs (AUC 0.65; 95% CI, 0.53-0.76), but levels at baseline and at 1 year were not associated with the HVPG response to NSBBs at 1 year. Conclusions: Serum miR-181b-5p is a promising non-invasive biomarker to identify patients with compensated cirrhosis at risk of ascites development. Lay summary: Ascites marks the transition from the compensated to decompensated stage in cirrhosis and indicates a worsening in prognosis. There are currently no easily accessible tools to identify patients with compensated cirrhosis at risk of developing ascites. We evaluated the levels of novel molecules termed microRNAs in the blood of patients with compensated cirrhosis and observed that miR-181b-5p can predict which patients are going to develop ascites

Serum miR-181b-5p predicts ascites onset in patients with compensated cirrhosis.

Background & Aims Treatment with non-selective beta-blockers (NSBBs) reduces the risk of ascites, which is the most common decompensating event in cirrhosis. This study aimed to assess the ability of a serum microRNA (miRNA) signature to predict ascites formation and the hemodynamic response to NSBBs in compensated cirrhosis. Methods Serum levels of miR-452-5p, miR-429, miR-885-5p, miR-181b-5p, and miR-122-5p were analyzed in patients with compensated cirrhosis (N = 105). Hepatic venous pressure gradient (HVPG) was measured at baseline, after intravenous propranolol, and 1 year after randomization to NSBBs (n = 52) or placebo (n = 53) (PREDESCI trial). miRNAs were analyzed at baseline and at 1 year. Results Nineteen patients (18%) developed ascites, of whom 17 developed ascites after 1 year. miR-181b-5p levels at 1 year, but not at baseline, were higher in patients that developed ascites. The AUC of miR-181b-5p at 1 year to predict ascites was 0.7 (95% CI 0.59-0.78). miR-429 levels were lower at baseline in acute HVPG responders to NSBBs (AUC 0.65; 95% CI, 0.53-0.76), but levels at baseline and at 1 year were not associated with the HVPG response to NSBBs at 1 year. Conclusions Serum miR-181b-5p is a promising non-invasive biomarker to identify patients with compensated cirrhosis at risk of ascites development. Lay summary Ascites marks the transition from the compensated to decompensated stage in cirrhosis and indicates a worsening in prognosis. There are currently no easily accessible tools to identify patients with compensated cirrhosis at risk of developing ascites. We evaluated the levels of novel molecules termed microRNAs in the blood of patients with compensated cirrhosis and observed that miR-181b-5p can predict which patients are going to develop ascites

Metabolomics as a tool to predict the risk of decompensation or liver related death in patients with compensated cirrhosis.

BACKGROUND AIMS Patients with compensated cirrhosis with clinically significant portal hypertension (CSPH: HVPG >10 mmHg) have a high risk of decompensation. HVPG is, however, an invasive procedure not available in all centers. The present study aims to assess whether metabolomics can improve the capacity of clinical models in predicting clinical outcome in these compensated patients. APPROACH RESULTS This is a nested study from the PREDESCI cohort (a RCT of non-selective beta blockers (NSBB) versus placebo in 201 patients with compensated cirrhosis and CSPH) including 167 patients for whom a blood sample was collected. A targeted metabolomic serum analysis, using UHPLC-MS, was performed. Metabolites underwent univariate time-to event cox regression analysis. Top ranked metabolites were selected using LogRank P-value to generate a stepwise cox model. Comparison between models was done using DeLong's test. Eighty-two patients with CSPH were randomized to NSBB and 85 to placebo. Thirty-three patients developed the main endpoint (decompensation/liver-related death). The model including HVPG, Child-Pugh and treatment received (HVPG/Clinical model) had a C-index of 0.748 [CI95% 0.664-0.827]. Addition of two metabolites, Ceramide (d18:1/22:0) and Methionine (HVPG/Clinical/Metabolite model) significantly improved model's performance (C-index of 0.808 [CI95% 0.735-0.882]; P=0.032). The combination of these two metabolites together with Child-Pugh and type of treatment received (Clinical/Metabolite model) had a C-Index of 0.785 [CI95% 0.710-0.860] not significantly different from the HVPG based models including or not metabolites. CONCLUSIONS In patients with compensated cirrhosis and CSPH, metabolomics improves the capacity of clinical models and achieves similar predictive capacity than models including HVPG

Adequacy of early-stage breast cancer systemic adjuvant treatment to Saint Gallen-2013 statement: the MCC-Spain study

The St Gallen Conference endorsed in 2013 a series of recommendations on early breast cancer treatment. The main purpose of this article is to ascertain the clinical factors associated with St Gallen-2013 recommendations accomplishment. A cohort of 1152 breast cancer cases diagnosed with pathological stage < 3 in Spain between 2008 and 2013 was begun and then followed-up until 2017/2018. Data on patient and tumour characteristics were obtained from medical records, as well as their first line treatment. First line treatments were classified in three categories, according on whether they included the main St Gallen-2013 recommendations, more than those recommended or less than those recommended. Multinomial logistic regression models were carried out to identify factors associated with this classification and Weibull regression models were used to find out the relationship between this classification and survival. About half of the patients were treated according to St Gallen recommendations; 21% were treated over what was recommended and 33% received less treatment than recommended. Factors associated with treatment over the recommendations were stage II (relative risk ratio [RRR] = 4.2, 2.9-5.9), cancer positive to either progesterone (RRR = 8.1, 4.4-14.9) or oestrogen receptors (RRR = 5.7, 3.0-11.0). Instead, factors associated with lower probability of treatment over the recommendations were age (RRR = 0.7 each 10 years, 0.6-0.8), poor differentiation (RRR = 0.09, 0.04-0.19), HER2 positive (RRR = 0.46, 0.26-0.81) and triple negative cancer (RRR = 0.03, 0.01-0.11). Patients treated less than what was recommended in St Gallen had cancers in stage 0 (RRR = 21.6, 7.2-64.5), poorly differentiated (RRR = 1.9, 1.2-2.9), HER2 positive (RRR = 3.4, 2.4-4.9) and luminal B-like subtype (RRR = 3.6, 2.6-5.1). Women over 65 years old had a higher probability of being treated less than what was recommended if they had luminal B-like, HER2 or triple negative cancer. Treatment over St Gallen was associated with younger women and less severe cancers, while treatment under St Gallen was associated with older women, more severe cancers and cancers expressing HER2 receptors

Changes in Individual and Contextual Socio-Economic Level Influence on Reproductive Behavior in Spanish Women in the MCC-Spain Study

Background: The association between socioeconomic level and reproductive factors has been widely studied. For example, it is well known that women with lower socioeconomic status (SES) tend to have more children, the age at first-born being earlier. However, less is known about to what extent the great socioeconomic changes occurred in a country (Spain) could modify women reproductive factors. The main purpose of this article is to analyze the influence of individual and contextual socioeconomic levels on reproductive factors in Spanish women, and to explore whether this influence has changed over the last decades. Methods: We performed a cross-sectional design using data from 2038 women recruited as population-based controls in an MCC-Spain case-control study. Results: Higher parent's economic level, education level, occupational level and lower urban vulnerability were associated with higher age at first delivery and lower number of pregnancies. These associations were stronger for women born after 1950: women with unfinished primary education had their first delivery 6 years before women with high education if they were born after 1950 (23.4 vs. 29.8 years) but only 3 years before if they were born before 1950 (25.7 vs. 28.0 years). For women born after 1950, the number of pregnancies dropped from 2.1 (unfinished primary school) to 1.7 (high education), whereas it remained almost unchanged in women born before 1950. Conclusions: Reproductive behavior was associated with both individual and area-level socio-economic indicators. Such association was stronger for women born after 1950 regarding age at first delivery and number of pregnancies and for women born before 1950 regarding consumption of hormonal contraceptives or postmenopausal therapy

Laboratorio de creación poética: un espacio colaborativo de escritura en la universidad

Este proyecto ha consistido en el desarrollo durante el curso 2023-2024 de un espacio colaborativo de escritura de poesía dirigido a estudiantes de distintos grados y másteres de la UCM. Se ha llevado a cabo un trabajo mensual colectivo de taller, seminarios de formación práctica, encuentros con poetas contemporáneas y publicaciones.Depto. de Lengua Española y Teoría de la LiteraturaFac. de FilologíaFALSEsubmitte