IGTP - Instituto de Investigación en Ciencias de la Salud Germans Trias i Pujol (Cataluña)

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12105/16971

El Instituto de Investigación Germans Trias i Pujol (IGTP) es un centro de investigación público situado en Badalona (Barcelonés) y que tiene como objetivo principal incrementar el conocimiento científico para, a continuación, transformarlo en una mejora en salud y en atención médica de los pacientes y de la comunidad. El Instituto de Investigación Germans Trias i Pujol lleva a cabo la investigación en grandes áreas como Ciencias de la conducta y abuso de sustancias, inmunología e inflamación, Enfermedades cardiovasculares y respiratorias, enfermedades infecciosas, enfermedades endocrinas y del metabolismo, de los huesos y de los riñones, enfermedades del hígado y del aparato digestivo, Cáncer, neurociencias y salud comunitaria. Acreditado por el Instituto de Salud Carlos III como Instituto de Investigación Sanitaria en 2009, y renovando esta acreditación cada 5 años, forma parte así del total de 34 Institutos de Investigación Sanitaria acreditados existentes en la actualidad.

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Sex differences in the comorbidity of patients seeking a first treatment for Alcohol Use Disorder
(Springer, 2023) García-Marchena, Nuria; Sanvisens, Arantza; Abellí-Deulofeu, Enric; Blanes, Rafael; Torrens, Marta; Miquel, Laia; Rubio, Gabriel; Bolao, Ferran; Muga, Robert; Zuluaga, Paola; Fuster, Daniel; Hernández-Rubio, Anna; Farre, Magi; Papasseit, Esther; Pérez-Mañá, Clara; Poyatos, Lourdes; Moranta, Catalina; Sion, Ana; Ortega, Lluisa; Bruguera, Pol; Caballeria, Elsa; Messeguer, Ana; Fonseca, Francina; Mestre-Pinto, Joan-Ignasi; Alías, María; Dinamarca, Fernando; Rodríguez-Fonseca, Fernando; Pavón-Morón, Francisco Javier; Marcos, Miguel; Martín, Candelaria; Pérez-Hernández, Onán; Manzanares, Jorge; Navarrete, Francisco; Gasparyan, Ani
Background: The CohRTA multicenter study aims to characterize patients undergoing a first treatment for alcohol use disorder (AUD). The objective is to analyze sex-specific differences in the comorbidity of AUD when starting the first treatment for the disorder. Methods: A multicenter study was carried out between 2014 and 2021 in 6 public centers in Spain. Sociodemographic characteristics were collected, variables related to alcohol consumption, medical comorbidity according to Cumulative Illness Rating Scale-Substance Abuse (CIRS-SA), antecedent of psychiatric comorbidity, general blood test and screening for drugs in urine. Logistic regression models were used to establish associations. Results: A total of 896 patients (634 M, 262 W) were included. Median age at admission was 48 years [IQR:41ﾖ56 years]. Men reported beginning regular alcohol consumption at an earlier age and drank more alcohol. The most frequent medical comorbidities were hepatic, respiratory, vascular and neurological. The median number of affected systems was three, with no differences between men and women. However, depressive disorder was more frequent in women. In the multivariate analysis, women were up to 4 times more likely to have a major depressive disorder, elevated ESR and elevated total cholesterol than men. Men started alcohol consumption earlier, had a higher body mass index (BMI), a higher probability of using cocaine and a higher frequency of GGT and bilirubin alteration than women. Conclusion: Differences by sex were found among individuals beginning first treatment for AUD. These differences must be taken into account when designing specific therapeutic strategies for men and women.
Dynamic changes in circulating tumor DNA assessed by shallow whole-genome sequencing associate with clinical efficacy of checkpoint inhibitors in NSCLC
(Wiley, 2023-05) Carbonell, Caterina; Frigola, Joan; Pardo, Nuria; Callejo, Ana; Iranzo, Patricia; Valdivia, Augusto; Priano, Ilaria; Cedrés, Susana; Martinez-Marti, Alex; Navarro, Alejandro; Lenza, Laura; Soleda, Mireia; Gonzalo-Ruiz, Javier; Vivancos, Ana; Sansó, Miriam; Carcereny, Enric; Morán, Teresa; Amat, Ramon; Felip, Enriqueta
Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis are the main therapeutic option for patients with advanced non-small cell lung cancer (NSCLC) without a druggable oncogenic alteration. Nevertheless, only a portion of patients benefit from this type of treatment. Here, we assessed the value of shallow whole-genome sequencing (sWGS) on plasma samples to monitor ICI benefit. We applied sWGS on cell-free DNA (cfDNA) extracted from plasma samples of 45 patients with metastatic NSCLC treated with ICIs. Over 150 samples were obtained before ICI treatment initiation and at several time points throughout treatment. From sWGS data, we computed the tumor fraction (TFx) and somatic copy number alteration (SCNA) burden and associated them with ICI benefit and clinical features. TFx at baseline correlated with metastatic lesions at the bone and the liver, and high TFx (≥ 10%) associated with ICI benefit. Moreover, its assessment in on-treatment samples was able to better predict clinical efficacy, regardless of the TFx levels at baseline. Finally, for a subset of patients for whom SCNA burden could be computed, increased burden correlated with diminished benefit following ICI treatment. Thus, our data indicate that the analysis of cfDNA by sWGS enables the monitoring of two potential biomarkers-TFx and SCNA burden-of ICI benefit in a cost-effective manner, facilitating multiple serial-sample analyses. Larger cohorts will be needed to establish its clinical potential.
Impact of the 2008 economic crisis on the burden of hepatitis B and C diseases in Southern European countries
(BioMed Central (BMC), 2024-06-20) Palladino, Claudia; Ramis, Rebeca; Ezeonwumelu, Ifeanyi Jude; Biondi, Antonio; Carreras, Giulia; Fischer, Florian; Gallus, Silvano; Golinelli, Davide; Gorini, Giuseppe; Hassan, Shoaib; Kabir, Zubair; Koyanagi, Ai; Lazarus, Jeffrey V; Mentis, Alexios-Fotios A; Meretoja, Tuomo J; Mokdad, Ali H; Monasta, Lorenzo; Mulita, Francesk; Postma, Maarten J; Tabarés-Seisdedos, Rafael; Thiyagarajan, Arulmani; Taveira, Nuno; Briz, Veronica; GBD 2019 Southern Europe Hepatitis B & C Collaborators; Bill & Melinda Gates Foundation
Background: The economic crisis that began in 2008 has severely affected Southern (Greece, Italy, Portugal, Spain) Western European (SWE) countries of Western Europe (WE) and may have affected ongoing efforts to eliminate viral hepatitis. This study was conducted to investigate the impact of the economic crisis on the burden of HBV and HCV disease. Methods: Global Burden of Diseases 2019 data were used to analyse the rates of epidemiological metrics of HBV and HCV acute and chronic infections in SWE and WE. Time series modelling was performed to quantify the impact of healthcare expenditure on the time trend of HBV and HCV disease burden in 2000-2019. Results: Declining trends in incidence and prevalence rates of acute HBV (aHBV) and chronic HBV were observed in SWE and WE, with the pace of decline being slower in the post-austerity period (2010-2019) and mortality due to HBV stabilised in SWE. Acute HCV (aHCV) metrics and chronic HCV incidence and mortality showed a stable trend in SWE and WE, whereas the prevalence of chronic HCV showed an oscillating trend, decreasing in WE in 2010-2019 (p < 0.001). Liver cancer due to both hepatitis infections showed a stagnant burden over time. An inverse association was observed between health expenditure and metrics of both acute and chronic HBV and HCV. Conclusions: Epidemiological metrics for HBV and HCV showed a slower pace of decline in the post-austerity period with better improvement for HBV, a stabilisation of mortality and a stagnant burden for liver cancer due to both hepatitis infections. The economic crisis of 2008 had a negative impact on the burden of hepatitis B and C. Elimination of HBV and HCV by 2030 will be a major challenge in the SWE countries.
Prevalence and associations of metabolic syndrome in patients with alcohol use disorder
(Nature Publishing Group, 2022-02-16) Hernández-Rubio, Anna; Sanvisens, Arantza; Bolao, Ferran; Cachon-Suarez, Isabel; Garcia-Martin, Carme; Short, Antoni; Bataller, Ramon; Muga, Roberto
Excessive alcohol consumption has been associated with different components of the metabolic syndrome (MetS) such as arterial hypertension, dyslipidemia, type 2 diabetes or obesity. We aimed to analyze the prevalence and associations of MetS in patients with Alcohol Use Disorder (AUD). Cross-sectional study in heavy drinkers admitted for the treatment of AUD between 2013 and 2017. Medical comorbidity, anthropometric data, alcohol use and biological parameters were obtained. MetS was established according to the harmonized definition. A total of 728 patients (22% women) were included; median age was 47 years (IQR: 40-53.5), median alcohol consumption was 160 g/day (IQR: 115-240) and prevalence of MetS was 13.9%. The multivariate analysis showed a significant dose-response effect of estimated glomerular filtration (eGFR) and MetS: relative to patients with eGFR > 90 mL/min, those with eGFR (60-90 mL/min) and those with eGFR < 60 mL/min were 1.93 times (95% CI 1.18-3.15) and 5.61 times (95% CI 1.66-19.0) more likely to have MetS, respectively. MetS was significantly associated with hyperuricemia (OR 2.28, 95% CI 1.36-3.82) and elevated serum GGT (OR 3.67, 95% CI 1.80-7.46). Furthermore, for every increase of 1 year in age, the probability of MetS increased significantly (OR 1.03, 95% CI 1.01-1.05). MetS in heavy drinkers is independently associated with reduced kidney function and metabolic risk factors including hyperuricemia and elevated serum GGT.
Gut to lung translocation and antibiotic mediated selection shape the dynamics of Pseudomonas aeruginosa in an ICU patient
(Nature Publishing Group, 2022-11-22) Wheatley, Rachel M; Diaz Caballero, Julio; van der Schalk, Thomas E; de Winter, Fien HR; Shaw, Liam P; Kapel, Natalia; Recanatini, Claudia; Timbermont, Leen; Kluytmans, Jan; Esser, Mark; Lacoma, Alicia; Prat-Aymerich, Cristina; Oliver, Antonio; Kumar-Singh, Samir; Malhotra-Kumar, Surbhi; Craig MacLean, R
Bacteria have the potential to translocate between sites in the human body, but the dynamics and consequences of within-host bacterial migration remain poorly understood. Here we investigate the link between gut and lung Pseudomonas aeruginosa populations in an intensively sampled ICU patient using a combination of genomics, isolate phenotyping, host immunity profiling, and clinical data. Crucially, we show that lung colonization in the ICU was driven by the translocation of P. aeruginosa from the gut. Meropenem treatment for a suspected urinary tract infection selected for elevated resistance in both the gut and lung. However, resistance was driven by parallel evolution in the gut and lung coupled with organ specific selective pressures, and translocation had only a minor impact on AMR. These findings suggest that reducing intestinal colonization of Pseudomonas may be an effective way to prevent lung infections in critically ill patients.
Detection and Prevalence of Macrolide and Fluoroquinolone Resistance in Mycoplasma genitalium in Badalona, Spain
(Multidisciplinary Digital Publishing Institute (MDPI), 2022-04) Rivaya, Belen; Le Roy, Chloe; Jordana-Lluch, Elena; Fernandez-Rivas, Gema; Casan, Cristina; Gonzalez, Victoria; Wang-Wang, Jun Hao; Bebear, Cecile; Matas, Lurdes; Pereyre, Sabine
Macrolide and fluoroquinolone resistance (MLr/FQr) in Mycoplasma genitalium (MG) infections is concerning worldwide. Current guidelines recommend performing MLr detection in MG-positive cases to adjust antimicrobial therapy. We aimed to evaluate the usefulness of PCR followed by pyrosequencing for MLr detection in comparison with a one-step commercial assay and to assess the prevalence of MLr and FQr in Badalona, Spain. A total of 415 MG-positive samples by Allplex STI-7 (Seegene) were analyzed for MLr detection by pyrosequencing. From those, 179 samples were further analyzed for MG and MLr by ResistancePlus® MG kit (SpeeDx) and 100 of them also for fluoroquinolone resistance (FQr) by sequencing the parC gene. Regarding MG detection, Allplex and Resistance Plus® showed an overall agreement of 87%, but this value rose to 95.4% if we compare them for MLr detection. Prevalence of MLr was 23.1% in Badalona, but this rate increased to 73.7% in the HIV-positive patients cohort. FQr detection showed 3% of resistant strains. Pyrosequencing is a convenient and cheap technique for MLr detection, but one-step tools should be considered in high-throughput laboratories. Despite the fact that MLr remained moderate and FQr was low in our study, simultaneous MG and MLr detection would improve patient's management applying resistance-guided treatment strategies.
A Polygenic Risk Score Based on a Cardioembolic Stroke Multitrait Analysis Improves a Clinical Prediction Model for This Stroke Subtype
(Frontiers Media, 2022) Cárcel-Márquez, Jara; Muiño, Elena; Gallego-Fabrega, Cristina; Cullell, Natalia; Lledós, Miquel; Llucià-Carol, Laia; Sobrino, Tomas; Campos, Francisco; Castillo, José; Freijo Guerrero, Maria del Mar; Arenillas, Juan Francisco; Obach, Victor; Álvarez-Sabín, José; Molina, Carlos A; Ribo, Marc; Jiménez-Conde, Jordi; Roquer, Jaume; Muñoz-Narbona, Lucia; Lopez-Cancio, Elena; Millán, Mònica; Diaz Navarro, Rosa; Vives-Bauza, Cristofol; Serrano-Heras, Gemma; Segura, Tomas; Ibañez, Laura; Heitsch, Laura; Delgado, Pilar; Dhar, Rajat; Krupinski, Jerzy; Delgado-Mederos, Raquel; Prats-Sánchez, Luis; Camps-Renom, Pol; Blay, Natalia; Sumoy, Lauro; de Cid, Rafael; Montaner, Joan; Cruchaga, Carlos; Lee, Jin-Moo; Martí-Fàbregas, Joan; Fernandez-Cadenas, Israel; Cárcel-Márquez, Jara; Muiño, Elena; Gallego-Fabrega, Cristina; Cullell, Natalia; Lledós, Miquel; Llucià-Carol, Laia; Sobrino, Tomas; Campos, Francisco; Castillo, José; Freijo Guerrero, Maria del Mar; Arenillas, Juan Francisco; Obach, Victor; Álvarez-Sabín, José; Molina, Carlos A; Ribo, Marc; Jiménez-Conde, Jordi; Roquer, Jaume; Muñoz-Narbona, Lucia; Lopez-Cancio, Elena; Millán, Mònica; Diaz Navarro, Rosa; Vives-Bauza, Cristofol; Serrano-Heras, Gemma; Segura, Tomas; Ibañez, Laura; Heitsch, Laura; Delgado, Pilar; Dhar, Rajat; Krupinski, Jerzy; Delgado-Mederos, Raquel; Prats-Sánchez, Luis; Camps-Renom, Pol; Blay, Natalia; Sumoy, Lauro; de Cid, Rafael; Montaner, Joan; Cruchaga, Carlos; Lee, Jin-Moo; Martí-Fàbregas, Joan; Fernandez-Cadenas, Israel
Background: Occult atrial fibrillation (AF) is one of the major causes of embolic stroke of undetermined source (ESUS). Knowing the underlying etiology of an ESUS will reduce stroke recurrence and/or unnecessary use of anticoagulants. Understanding cardioembolic strokes (CES), whose main cause is AF, will provide tools to select patients who would benefit from anticoagulants among those with ESUS or AF. We aimed to discover novel loci associated with CES and create a polygenetic risk score (PRS) for a more efficient CES risk stratification. Methods: Multitrait analysis of GWAS (MTAG) was performed with MEGASTROKE-CES cohort (n = 362,661) and AF cohort (n = 1,030,836). We considered significant variants and replicated those variants with MTAG p-value < 5 × 10-8 influencing both traits (GWAS-pairwise) with a p-value < 0.05 in the original GWAS and in an independent cohort (n = 9,105). The PRS was created with PRSice-2 and evaluated in the independent cohort. Results: We found and replicated eleven loci associated with CES. Eight were novel loci. Seven of them had been previously associated with AF, namely, CAV1, ESR2, GORAB, IGF1R, NEURL1, WIPF1, and ZEB2. KIAA1755 locus had never been associated with CES/AF, leading its index variant to a missense change (R1045W). The PRS generated has been significantly associated with CES improving discrimination and patient reclassification of a model with age, sex, and hypertension. Conclusion: The loci found significantly associated with CES in the MTAG, together with the creation of a PRS that improves the predictive clinical models of CES, might help guide future clinical trials of anticoagulant therapy in patients with ESUS or AF.
New Metrics to Assess Type 2 Diabetes after Bariatric Surgery: The Time-Within-Remission Range
(Multidisciplinary Digital Publishing Institute (MDPI), 2020-04) de Hollanda, Ana; Lecube, Albert; Rubio, Miguel Angel; Sanchez, Enric; Vilarrasa, Nuria; Oliva, Jose Gregorio; Fernandez-Soto, Maria Luisa; Salas-Salvado, Jordi; Ballesteros-Pomar, Maria D.; Ciudin, Andreea; Torres, Ferran; Vidal, Concepcion; Morales, Maria Jose; Valdes, Sergio; Pellitero, Silvia; Minambres, Inka; Masmiquel, Lluis; Goday, Albert; Suarez, Lorena; Flores, Liliam; Bueno, Marta; Caixas, Assumpta; Breton, Irene; Camara, Rosa; Olbeyra, Romina; Penso, Rona; de la Cruz, Maria Jose; Simo-Servat, Andreu; Pereyra-Garcia, Francisca Maria; Lopez-Mezquita, Elena Teresa; Gils, Anna; Fidilio, Enzamaria; Bandres, Orosia; Martinez, Angel; Abuin, Jose; Marques-Pamies, Montserrat; Tuneu, Laura; Arteaga, Magdalena; Castaner, Olga; Goñi, Fernando; Arrizabalaga, Cristina; Antonio Botana, Manuel; Calanas, Alfonso; Rebollo, Angel
Almost one third of patients do not achieve type 2 diabetes remission after bariatric surgery or are unable to sustain this effect long term. Our objective was to delve further into the dynamic responses of diabetes after bariatric surgery and to evaluate the time-within-remission range as a variable of metabolic control. A descriptive cohort study was done using a computerised multicentre and multidisciplinary registry. All data were adjusted by propensity score. A total of 1186 subjects with a follow-up of 4.5 +/- 2.5 years were included. Type of surgery, diabetes remission, recurrence of diabetes, time-within-remission range and key predictors of diabetes outcomes were assessed. All patients (70% women, 51.4 +/- 9.2 years old, body mass index (BMI) 46.3 +/- 6.9 kg/m(2)) underwent primary bariatric procedures. Time-within-remission range were 83.3% (33.3-91.6) after gastric bypass, 68.7% (7.1-87.5) after sleeve gastrectomy and 90% (83.3-92.8) after malabsorptive techniques (p < 0.001 for all). Duration of diabetes, baseline HbA1c and insulin treatment were significantly negatively correlated with the time-within-remission range. The association of bariatric techniques with time-within-remission range, using gastric bypass as a reference, were: odds ratio (OR) 3.70 (2.34-5.84), p < 0.001 for malabsorptive techniques and OR 0.55 (0.40-0.75), p < 0.001 for sleeve gastrectomy. Characteristics of type 2 diabetes powerfully influence the outcomes of bariatric surgery. The time-within-remission range unveils a superiority of gastric bypass compared to sleeve gastrectomy.
Early diagnosis of HIV in Primary Care in Spain. Results of a pilot study based on targeted screening based on indicator conditions, behavioral criteria and region of origin
(Elsevier, 2018-03) Agusti, Cristina; Martin-Rabadan Muro, Maria; Zarco, Jose; Aguado, Cristina; Carrillo, Ricard; Codinach, Roger; Manuel Carmona, Jose; Casabona, Jordi
Objectives: To estimate the prevalence of HIV infection in patients diagnosed with an indicator condition (IC) for HIV and/or risk behavior for their acquisition and/or coming from high prevalence countries. To determine the acceptability and feasibility of offering HIV testing based on IC and behavioral and origin criteria in Primary Care (PC). Design: Cross-sectional study in a convenience sample. Location: Six PC centers in Spain. Participants: The inclusion criteria were: patients between 16 and 65 years old who presented at least one of the proposed ICs and/or at least one of the proposed behavioral and/or origin criteria. A total of 388 patients participated. Intervention: HIV serology was offered to all patients who met the inclusion criteria. Main measurements: Description of IC frequency, behavioral and origin criteria. Prevalence of HIV infection. Level of acceptability and feasibility of the HIV screening based on IC and behavioral and origin criteria. Results: A total of 174 patients had an IC (44.84%). The most common behavioral criterion was: having unprotected sex at some time in life with people who did not know their HIV status (298; 76.8%). Four HIV+ patients (1.03%) were diagnosed. All had an IC and were men who had sex with men. The level of acceptability in PC was high. Conclusions: Offering HIV testing to patients with IC and behavioral criteria is feasible and effective in PC.
A Biomarker to Differentiate between Primary and Cocaine-Induced Major Depression in Cocaine Use Disorder: The Role of Platelet IRAS/Nischarin (I-1-Imidazoline Receptor)
(Frontiers Media, 2017-12-01) Keller, Benjamin; Mestre-Pinto, Joan-Ignasi; Alvaro-Bartolome, Maria; Martinez-Sanvisens, Diana; Farre, Magi; Julia Garcia-Fuster, M; Garcia-Sevilla, Jesus A; Torrens, Marta; NEURODEP Grp
The association of cocaine use disorder (CUD) and comorbid major depressive disorder (MDD; CUD/MDD) is characterized by high prevalence and poor treatment outcomes. CUD/MDD may be primary (primary MDD) or cocaine-induced (CUD-induced MDD). Specific biomarkers are needed to improve diagnoses and therapeutic approaches in this dual pathology. Platelet biomarkers [5-HT2A receptor and imidazoline receptor antisera selected (IRAS)/nischarin] were assessed by Western blot in subjects with CUD and primary MDD (n = 16) or CUD-induced MDD (n = 9; antidepressant free, AD-; antidepressant treated, AD+) and controls (n = 10) at basal level and/or after acute tryptophan depletion (ATD). Basal platelet 5-HT2A receptor (monomer) was reduced in comorbid CUD/MDD subjects (all patients: 43%) compared to healthy controls, and this down-regulation was independent of AD medication (decreases in AD-: 47%, and in AD+: 40%). No basal differences were found for IRAS/nischarin contents in AD+ and AD-comorbid CUD/MDD subjects. The comparison of IRAS/nischarin in the different subject groups during/after ATD showed opposite modulations (i.e., increases and decreases) in response to low plasma tryptophan levels with significant differences discriminating between the subgroups of CUD with primary MDD and CUD-induced MDD. These specific alterations suggested that platelet IRAS/nischarin might be useful as a biomarker to discriminate between primary and CUD-induced MDD in this dual pathology.
Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2
(Nature Publishing Group, 2024-02-19) Pérez-Jurado, Luis Alberto; Cáceres, Alejandro; Balagué-Dobón, Laura; Esko, Tonu; López de Heredia, Miguel; Quintela, Inés; Cruz, Raquel; Lapunzina, Pablo; Carracedo, Ángel; SCOURGE Cohort Group; González, Juan R; Meijome, Xose M; Brochado-Kith, Oscar; Ceballos, Francisco C; Fernandez-Rodriguez, Amanda; Jimenez-Sousa, Maria Angeles; Martin-Vicente, Maria; Resino, Salvador; Virseda-Berdices, Ana; Government of Catalonia (España); Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España); Ministerio de Ciencia e Innovación (España); Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Estonian Research Council; Instituto de Salud Carlos III; Amancio Ortega Foundation; Banco Santander
The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people.
Estimation of Improvements in Mortality in Spectrum Among Adults With HIV Receiving Antiretroviral Therapy in High-Income Countries
(Wolters Kluwer, 2024-01-01) Trickey, Adam; Glaubius, Robert; Pantazis, Nikos; Zangerle, Robert; Wittkop, Linda; Vehreschild, Janne; Grabar, Sophie; Cavassini, Matthias; Teira, Ramon; d'Arminio Monforte, Antonella; Casabona, Jordi; van Sighem, Ard; Jarrin Vera, Inmaculada; Ingle, Suzanne M; Sterne, Jonathan A C; Imai-Eaton, Jeffrey W; Johnson, Leigh F; NIH - National Institute on Alcohol Abuse and Alcoholism (NIAAA) (Estados Unidos); National Institute for Health Research (Reino Unido); Wellcome Trust; Gilead Sciences (Spain); Ministère de la Santé (Francia); Agence Nationale de Recherches sur le sida et les hépatites virales (Francia); Austrian Agency for Health and Food Safety; Stichting HIV Monitoring; Ministry of Health Welfare and Sport (Países Bajos); Centers for Disease Control and Prevention (Estado Unidos); German Center for Infection Research (Alemania); Instituto de Salud Carlos III; RETICS-Sida (RIS-ISCIII) (España); Plan Nacional de I+D+i (España); Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); ViiV Healthcare; Preben og Anna Simonsens Fond; Institut National de la Santé et de la Recherche Médicale (Francia); Janssen Cilag; Ministerio de Sanidad (España); Swiss National Science Foundation; United States Department of Veterans Affairs; NIH - National Institute of Allergy and Infectious Diseases (NIAID) (Estados Unidos); Joint United Nations Programme on HIV/AIDS; Bill & Melinda Gates Foundation; Merck KGaA; Pfizer; Astellas Pharma; University of Freiburg (Alemania); University of Manchester (Reino Unido); University of Bristol (Reino Unido); Universitätsklinikum Aachen (Alemania)
Introduction: Mortality rates for people living with HIV (PLHIV) on antiretroviral therapy (ART) in high-income countries continue to decline. We compared mortality rates among PLHIV on ART in Europe for 2016-2020 with Spectrum's estimates. Methods: The AIDS Impact Module in Spectrum is a compartmental HIV epidemic model coupled with a demographic population projection model. We used national Spectrum projections developed for the 2022 HIV estimates round to calculate mortality rates among PLHIV on ART, adjusting to the age/country distribution of PLHIV starting ART from 1996 to 2020 in the Antiretroviral Therapy Cohort Collaboration (ART-CC)'s European cohorts. Results: In the ART-CC, 11,504 of 162,835 PLHIV died. Between 1996-1999 and 2016-2020, AIDS-related mortality in the ART-CC decreased from 8.8 (95% CI: 7.6 to 10.1) to 1.0 (0.9-1.2) and from 5.9 (4.4-8.1) to 1.1 (0.9-1.4) deaths per 1000 person-years among men and women, respectively. Non-AIDS-related mortality decreased from 9.1 (7.9-10.5) to 6.1 (5.8-6.5) and from 7.0 (5.2-9.3) to 4.8 (4.3-5.2) deaths per 1000 person-years among men and women, respectively. Adjusted all-cause mortality rates in Spectrum among men were near ART-CC estimates for 2016-2020 (Spectrum: 7.02-7.47 deaths per 1000 person-years) but approximately 20% lower in women (Spectrum: 4.66-4.70). Adjusted excess mortality rates in Spectrum were 2.5-fold higher in women and 3.1-3.4-fold higher in men in comparison to the ART-CC's AIDS-specific mortality rates. Discussion: Spectrum's all-cause mortality estimates among PLHIV are consistent with age/country-controlled mortality observed in ART-CC, with some underestimation of mortality among women. Comparing results suggest that 60%-70% of excess deaths among PLHIV on ART in Spectrum are from non-AIDS causes.
A second update on mapping the human genetic architecture of COVID-19
(Nature Publishing Group, 2023-09) COVID-19 Host Genetics Initiative; Fernandez-Rodriguez, Amanda; Jimenez-Sousa, Maria Angeles; Ceballos, Francisco C; Resino, Salvador
Evolving spectrum but persistent high mortality of COVID-19 among patients on kidney replacement therapy in the vaccine era: the Spanish COVID-19 KRT Registry.
(2022-06-03) Quiroga, Borja; Ortiz, Alberto; Cabezas-Reina, Carlos Jesús; Ruiz Fuentes, María Carmen; López Jiménez, Verónica; Zárraga Larrondo, Sofía; Toapanta, Néstor; Molina Gómez, María; de Sequera, Patricia; Sánchez-Álvarez, Emilio; Spanish COVID-19 KRT Registry collaborative group
Kidney replacement therapy (KRT) conferred a high risk for coronavirus disease 2019 (COVID-19) related mortality early in the pandemic. We evaluate the presentation, treatment and outcomes of COVID-19 in patients on KRT over time during the pandemic. This registry-based study involved 6080 dialysis and kidney transplant (KT) patients with COVID-19, representing roughly 10% of total Spanish KRT patients. Epidemiology, comorbidity, infection, vaccine status and treatment data were recorded, and predictors of hospital admission, intensive care unit (ICU) admission and mortality were evaluated. Vaccine introduction decreased the number of COVID-19 cases from 1747 to 280 per wave. Of 3856 (64%) COVID-19 KRT patients admitted to the hospital, 1481/3856 (38%) were admitted during the first of six waves. Independent predictors for admission included KT and the first wave. During follow-up, 1207 patients (21%) died, 500/1207 (41%) during the first wave. Among vaccinated patients, mortality was 19%, mostly affecting KT recipients. Overall, independent predictors for mortality were older age, disease severity (lymphopaenia, pneumonia) and ICU rejection. Among patient factors, older age, male sex, diabetes, KT and no angiotensin receptor blockers (ARB) were independent predictors of death. In KT recipients, individual immunosuppressants were independent predictors of death. Over time, patient characteristics evolved and in later pandemic waves, COVID-19 was mainly diagnosed in vaccinated KT recipients; in the few unvaccinated dialysis patients, ICU admissions increased and mortality decreased (28% for the first wave and 16-22% thereafter). The clinical presentation and outcomes of COVID-19 during the first wave no longer represent COVID-19 in KRT patients, as the pandemic has become centred around vaccinated KT recipients. Vaccines lowered the incidence of diagnosed COVID-19 and mortality. However, mortality remains high despite increased access to ICU care.
Plasma Amino Acid Concentrations in Patients with Alcohol and/or Cocaine Use Disorders and Their Association with Psychiatric Comorbidity and Sex.
(2022-05-14) García-Marchena, Nuria; Marcos, Alberto; Flores-López, María; Moreno-Fernández, Mario; Requena-Ocaña, Nerea; Porras-Perales, Oscar; Torres-Galván, Sandra; Araos, Pedro; Serrano, Antonia; Muga, Roberto; Ruiz-Ruiz, Juan Jesús; Rodríguez de Fonseca, Fernando; Ambrosio, Emilio; Pavón-Morón, Francisco Javier
Background: Co-occurrence of mental and substance use disorders (SUD) is prevalent, but complicates their clinical courses, and specific biomarkers are required. Amino acids are altered in primary mental disorders; however, little is known about SUD and psychiatric comorbidity. Because most psychiatric disorders and biomarkers show sex differences, we investigated amino acids in men and women with alcohol and/or cocaine use disorders (AUD and/or CUD) and psychiatric comorbidity. Methods: A cross-sectional study was conducted in 295 participants, who were divided into four groups (AUD, n = 60; CUD, n = 41; AUD + CUD, n = 64; and control, n = 130). Participants were clinically assessed, and plasma amino acid concentrations were analyzed in relation to sex, diagnosis of SUD and psychiatric comorbidity Results: In the total sample, there were sex differences, and women showed lower Iso, Leu, Gln and Glu than men. While patients with CUD and AUD + CUD had higher Glu, Gly, Orn and Ser than controls, patients with AUD showed no differences. In SUD, patients with psychiatric comorbidity had lower Orn and higher Ala than non-comorbid patients in the AUD group. Conclusions: There was a dysregulation of plasma amino acids in abstinent patients with SUD. However, our results suggest the importance of considering the clinical characteristics and sex in the validity of amino acids as potential biomarkers for SUD.
Sex Differences in Plasma Lysophosphatidic Acid Species in Patients with Alcohol and Cocaine Use Disorders.
(2022-04-30) Flores-López, María; García-Marchena, Nuria; Araos, Pedro; Requena-Ocaña, Nerea; Porras-Perales, Oscar; Torres-Galván, Sandra; Suarez, Juan; Pizarro, Nieves; de la Torre, Rafael; Rubio, Gabriel; Ruiz-Ruiz, Juan Jesús; Rodríguez de Fonseca, Fernando; Serrano, Antonia; Pavón-Morón, Francisco Javier
Preclinical evidence suggests a main role of lysophosphatidic acid (LPA) signaling in drug addiction. Recently, we reported alterations in the plasma concentrations of LPA species in patients with alcohol use disorder (AUD). As there are sex differences in drug addiction, the main aim of the present study was to investigate whether relevant LPA species (16:0-LPA, 18:0-LPA, 18:1-LPA, 18:2-LPA and 20:4-LPA) were associated with sex and/or substance use disorder (SUD). This exploratory study was conducted in 214 abstinent patients with lifetime SUD, and 91 healthy control subjects. The SUD group was divided according to the diagnosis of AUD and/or cocaine use disorder (CUD). Participants were clinically assessed, and plasma samples were collected to determine LPA species and total LPA. We found that LPA concentrations were significantly affected by sex, and women showed higher concentrations than men. In addition, there were significantly lower 16:0-LPA, 18:2-LPA and total LPA concentrations in patients with SUD than in controls. Namely, patients with CUD and AUD + CUD showed lower LPA concentrations than controls or patients with AUD. In conclusion, our data suggest that LPA species could be potential biomarkers for SUD in women and men, which could contribute to a better stratification of these patients in treatment programs.
Vascular Endothelial Growth Factor as a Potential Biomarker of Neuroinflammation and Frontal Cognitive Impairment in Patients with Alcohol Use Disorder.
(2022-04-20) Requena-Ocaña, Nerea; Flores-Lopez, María; Papaseit, Esther; García-Marchena, Nuria; Ruiz, Juan Jesús; Ortega-Pinazo, Jesús; Serrano, Antonia; Pavón-Morón, Francisco Javier; Farré, Magí; Suarez, Juan; Rodríguez de Fonseca, Fernando; Araos, Pedro
Background: Alcohol Use Disorder (AUD) is associated with functional disruption of several brain structures that may trigger cognitive dysfunction. One of the mechanisms of alcohol-associated cognitive impairment has been proposed to arise from its direct impact on the immune system, which culminates in the release of cytokines and chemokines which can eventually reach the brain. Alcohol can also disrupt the blood-brain barrier, facilitating the penetration of pro-inflammatory molecules throughout vascular endothelial growth factor A (VEGFA). Thus, alcohol-induced alterations in chemokines and VEGFA might contribute to the neuroinflammation and cognitive impairment associated with AUD. Methods: The present cross-sectional study investigates whether patients with AUD (n = 86) present cognitive disability associated to alterations in plasma concentration of SDF-1, fractalkine, eotaxin, MCP-1, MIP-1α and VEGFA when compared to control subjects (n = 51). Results: The analysis indicated that SDF-1 and MCP-1 concentrations were higher in AUD patients than in controls. Concentrations of VEGFA were higher in AUD patients with severe frontal deficits, and the score of frontal lobe functions was negatively correlated with VEGFA and fractalkine. Acute alcohol effects on VEGFA plasma levels in healthy volunteers demonstrated the induction of VEGFA release by heavy alcohol drinking. VEGFA was positively correlated with pro-inflammatory chemokines in AUD patients with frontal cognitive impairment. Conclusions: we propose VEGFA/chemokine monitoring as biomarkers of potential cognitive impairment in AUD patients.
Impact of COVID-19 Lockdown in Eating Disorders: A Multicentre Collaborative International Study.
(2021-12-27) Baenas, Isabel; Etxandi, Mikel; Munguía, Lucero; Granero, Roser; Mestre-Bach, Gemma; Sánchez, Isabel; Ortega, Emilio; Andreu, Alba; Moize, Violeta L; Fernández-Real, Jose-Manuel; Tinahones, Francisco J; Diéguez, Carlos; Frühbeck, Gema; Le Grange, Daniel; Tchanturia, Kate; Karwautz, Andreas; Zeiler, Michael; Imgart, Hartmut; Zanko, Annika; Favaro, Angela; Claes, Laurence; Shekriladze, Ia; Serrano-Troncoso, Eduardo; Cecilia-Costa, Raquel; Rangil, Teresa; Loran-Meler, Maria Eulalia; Soriano-Pacheco, José; Carceller-Sindreu, Mar; Navarrete, Rosa; Lozano, Meritxell; Linares, Raquel; Gudiol, Carlota; Carratalà, Jordi; Plana, Maria T; Graell, Montserrat; González-Parra, David; Gómez-Del Barrio, José A; Sepúlveda, Ana R; Sánchez-González, Jéssica; Machado, Paulo P P; Håkansson, Anders; Túry, Ferenc; Pászthy, Bea; Stein, Daniel; Papezová, Hana; Gricova, Jana; Bax, Brigita; Borisenkov, Mikhail F; Popov, Sergey V; Gubin, Denis G; Petrov, Ivan M; Isakova, Dilara; Mustafina, Svetlana V; Kim, Youl-Ri; Nakazato, Michiko; Godart, Nathalie; van Voren, Robert; Ilnytska, Tetiana; Chen, Jue; Rowlands, Katie; Voderholzer, Ulrich; Monteleone, Alessio M; Treasure, Janet; Jiménez-Murcia, Susana; Fernández-Aranda, Fernando
The COVID-19 lockdown has had a significant impact on mental health. Patients with eating disorders (ED) have been particularly vulnerable. (1) To explore changes in eating-related symptoms and general psychopathology during lockdown in patients with an ED from various European and Asian countries; and (2) to assess differences related to diagnostic ED subtypes, age, and geography. The sample comprised 829 participants, diagnosed with an ED according to DSM-5 criteria from specialized ED units in Europe and Asia. Participants were assessed using the COVID-19 Isolation Scale (CIES). Patients with binge eating disorder (BED) experienced the highest impact on weight and ED symptoms in comparison with other ED subtypes during lockdown, whereas individuals with other specified feeding and eating disorders (OFSED) had greater deterioration in general psychological functioning than subjects with other ED subtypes. Finally, Asian and younger individuals appeared to be more resilient. The psychopathological changes in ED patients during the COVID-19 lockdown varied by cultural context and individual variation in age and ED diagnosis. Clinical services may need to target preventive measures and adapt therapeutic approaches for the most vulnerable patients.
CKD: The burden of disease invisible to research funders.
(2021-11-17) AIRG-E, EKPF, ALCER, FRIAT, REDINREN, RICORS2040, SENEFRO; SET, ONT
The uptake of the current concept of chronic kidney disease (CKD) by the public, physicians and health authorities is low. Physicians still mix up CKD with chronic kidney insufficiency or failure. In a recent manuscript, only 23% of participants in a cohort of persons with CKD had been diagnosed by their physicians as having CKD while 29% has a diagnosis of cancer and 82% had a diagnosis of hypertension. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. A prevalent view is that for those in whom kidneys fail, the problem is "solved" by dialysis or kidney transplantation. However, the main burden of CKD is accelerated aging and all-cause and cardiovascular premature death. CKD is the most prevalent risk factor for lethal COVID-19 and the factor that most increases the risk of death in COVID-19, after old age. Moreover, men and women undergoing KRT still have an annual mortality which is 10-100-fold higher than similar age peers, and life expectancy is shortened by around 40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth global cause of death by 2040 and the second cause of death in Spain before the end of the century, a time when 1 in 4 Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded CIBER network research structure in Spain. Leading Spanish kidney researchers grouped in the kidney collaborative research network REDINREN have now applied for the RICORS call of collaborative research in Spain with the support of the Spanish Society of Nephrology, ALCER and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true. However, only the highest level of research funding through the CIBER will allow to adequately address the issue before it is too late.
Influence of gender and education on cocaine users in an outpatient cohort in Spain
(Springer, 2021-10-22) Requena-Ocaña, Nerea; Flores-Lopez, María; San Martín, Alicia; García-Marchena, Nuria; Pedraz, María; Ruiz, Juan Jesús; Serrano, Antonia; Suarez, Juan; Pavón, Francisco Javier; Rodríguez de Fonseca, Fernando; Araos, Pedro; [Requena-Ocaña,N; Flores-Lopez,M; García-Marchena.N; Pedraz,M; Serrano,A; Suarez,J; Pavón,FJ; Rodríguez de Fonseca,F; Araos,P] Laboratorio de Medicina Regenerativa (LMR), Unidad de Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Málaga, Spain. [Requena-Ocaña,N; San Martín,A] Departamento de Psicobiología, Facultad de Psicología, Universidad Complutense de Madrid, Campus de Somosaguas, Pozuelo de Alarcón, Madrid, Spain. [García-Marchena,N] Institut D, Investigació en Ciències de la Salut Germans Trias i Pujol (IGTP), Unidad de Adicciones-Servicio de Medicina Interna, Campus Can Ruti, Carrer del Canyet s/n, 08916 Badalona, Spain. [Ruiz,JJ] Centro Provincial de Drogodependencias (CPD) de Málaga, Diputación de Málaga, C/Ana Solo de Zaldívar, Málaga, Spain. [Suarez,J] Department of Anatomy, Legal Medicine and History of Science, School of Medicine, University of Malaga, Boulevard Louis Pasteur, Málaga, Spain. [Pavón,FJ] Instituto de Investigación Biomédica de Málaga (IBIMA), Unidad de Gestión Clínica del Corazón, Hospital Universitario Virgen de la Victoria de Málaga, Malaga, Spain. [Pavón,FJ] Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Calle de Melchor Fernández Almagro, Madrid, Spain. [Araos,P] Departamento de Psicobiología y Metdología de las CC del Comportamiento, Facultad de Psicología, Universidad de Málaga, Málaga, Spain.
Gender significantly influences sociodemographic, medical, psychiatric and addiction variables in cocaine outpatients. Educational level may be a protective factor showing less severe addictive disorders, longer abstinence periods, and better cognitive performance. The aim was to estimate gender-based differences and the influence of educational level on the clinical variables associated with cocaine use disorder (CUD). A total of 300 cocaine-consuming patients undergoing treatments were recruited and assessed using the Psychiatric Research Interview for Substance and Mental Diseases according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Women developed CUD later but exhibited more consumption of anxiolytics, prevalence of anxiety disorders, eating disorders, and major depressive disorders. Alcohol and cannabis use disorders were more frequent in men. A predictive model was created and identified three psychiatric variables with good prognosis for distinguishing between women and men. Principal component analysis helped to describe the different profile types of men and women who had sought treatment. Low educational levels seemed to be a risk factor for the onset, development, and duration of CUD in both genders. Women and men exhibited different clinical characteristics that should be taken into account when designing therapeutic policies. The educational level plays a protective/risk role in the onset, development and progression of CUD, thus prolonging the years of compulsory education and implementing cognitive rehabilitation programmes could be useful.

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