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Polygenic risk scores mediating functioning outcomes through cognitive and clinical features in youth at family risk and controls
(Elsevier B.V., 2024-04) Segura, Alex G.; Serna, Elena de la, 1978-; Sugranyes Ernest, Gisela; Baeza, Inmaculada, 1970-; Valli, Isabel; Martínez Serrano, Irene; Díaz Caneja, Covadonga M.; Andreu-Bernabeu, Álvaro; Moreno, Dolores; Gassó Astorga, Patricia; Rodriguez Ferret, Natalia; Martínez Pinteño, Albert; Prohens Coll, Llucia; Torrent Font, Carla; García Rizo, Clemente; Mas, Sergi; Castro Fornieles, Josefina
Schizophrenia and bipolar disorder exhibit substantial clinical overlap, particularly in individuals at familial high risk, who frequently present sub-threshold symptoms before the onset of illness. Severe mental disorders are highly polygenic traits, but their impact on the stages preceding the manifestation of mental disorders remains relatively unexplored. Our study aimed to examine the influence of polygenic risk scores (PRS) on sub-clinical outcomes over a 2-year period in youth at familial high risk for schizophrenia and bipolar disorder and controls. The sample included 222 children and adolescents, comprising offspring of parents with schizophrenia (n = 38), bipolar disorder (n = 80), and community controls (n = 104). We calculated PRS for psychiatric disorders, neuroticism and cognition using the PRS-CS method. Linear mixed-effects models were employed to investigate the association between PRS and cognition, symptom severity and functioning. Mediation analyses were conducted to explore whether clinical features acted as intermediaries in the impact of PRS on functioning outcomes. SZoff exhibited elevated PRS for schizophrenia. In the entire sample, PRS for depression, neuroticism, and cognitive traits showed associations with sub-clinical features. The effect of PRS for neuroticism and general intelligence on functioning outcomes were mediated by cognition and symptoms severity, respectively. This study delves into the interplay among genetics, the emergence of sub-clinical symptoms and functioning outcomes, providing novel evidence on mechanisms underpinning the continuum from sub-threshold features to the onset of mental disorders. The findings underscore the interplay of genetics, cognition, and clinical features, providing insights for personalized early interventions.
Hepatitis C-related cirrhosis will be a marginal cause of hospital admissions by 2025
(Elsevier, 2020-12-01) Rodriguez-Tajes, Sergio; Pocurull Aparicio, Anna; Castillo Iturra, Joaquín; Casanova, Gherzon; Vega, Laia; Lens García, Sabela; Mariño, Zoe; Londoño, María Carlota; Forner González, Alejandro; Torres, Ferran; Forns, Xavier
Background & Aims Complications of cirrhosis are the main cause of hospital admissions in liver units. In areas where HCV is prevalent, most of these admissions are attributable to HCV-related cirrhosis (HCV-cirrhosis). This study assessed the impact of direct-acting antivirals (DAA) in the profile of patients with liver disease admitted to a referral liver unit from a university hospital. Methods We registered hospital admissions resulting from cirrhosis to the Liver Unit of the Hospital Clinic of Barcelona, from 2011 to 2014 (pre-DAA period) and from 2015 to 2019 (post-DAA period). Results From a total of 14,865 hospital admissions, 10,053 resulted from cirrhosis (corresponding to 6,272 patients). The number and proportion of hospital admissions because of HCV-cirrhosis remained stable during the period 2011–2014 (525 per year, 48.8% of the total), but decreased progressively after 2015 (p <0.001), reaching <300 (27.1%) admissions in 2019. Similarly, HCV-cirrhosis accounted for 3,885 inpatient days per year (44.9%) during the pre-DAA period and decreased steadily after 2015 (p >0.001), reaching only 1,909 inpatient days (22%) in 2019. The figures for intensive care unit admissions followed a similar pattern. By means of a slope analysis (binomial regression model), we predicted that HCV-cirrhosis hospital admissions will be residual by 2025 (2.3%, 95% CI 0–10.9%). By contrast, we observed a significant increase in hospital admissions because of metabolic-associated fatty liver disease (5-fold) and autoimmune hepatitis (4-fold) during the study period. Conclusions In summary, our data showed a profound reduction in HCV-cirrhosis hospitalisation burden since 2015, coincident with the wide use of DAAs in Spain. Our predictions suggest that, by 2025, HCV-cirrhosis will be a marginal cause of hospital admissions for patients with liver disease. Lay summary Over the past few years, the wide use of antiviral drugs that cure HCV has had a significant effect on patients being admitted to hospital. Most patients with HCV and cirrhosis are treated (and often cured) in the community and, thus, the number of hospital admissions because of severe forms of HCV has decreased drastically. HCV is no longer the first cause of admission into liver units and, in only a few years from now, it is likely to be only a residual cause of hospitalisation.
Risk factors in severe anaphylaxis: which matters the most, food or cofactors?
(Esmon Publicidad S.A., 2022) Casas Saucedo, Rocio; Cruz, Cinthia de la; Araujo Sánchez, Giovanna; Gelis, Sònia; Jimenez, T.; Riggioni, S.; San Bartolome, Clara; Pascal i Capdevila, Mariona; Bartra Tomàs, Joan; Muñoz-Cano, Rosa
Background: The prevalence of anaphylactic shock, the most severe manifestation of anaphylaxis, remains unknown. Risk factors and biomarkers have not been fully identified. Objective: To identify risk factors in patients who experience anaphylactic shock. Methods: Using lipid transfer protein (LTP) allergy as a model, we compared the characteristics of patients who developed anaphylaxis and anaphylactic shock. We recorded demographics, pollen sensitization, foods ingested up to 2 hours before onset of the reaction, and the presence of cofactors. Culprit foods were identified through a compatible clinical history and positive allergology work-up (skin prick test and/or sIgE). Results: We evaluated 150 reactions in 55 patients with anaphylaxis (134 reactions) and 12 with anaphylactic shock (16 reactions). Patients in the anaphylaxis group experienced twice as many reactions (mean [SD], 2.4 [2.5] for anaphylaxis vs 1.3 [1.5] for anaphylactic shock; P<.02). No relationship was found between any food group and severity of the reaction. The most frequent food involved in both groups of patients was the combination of several plant-derived foods (plant food mix), followed by peach and nuts. Indeed, in the reactions caused by plant food mix, the presence of a cofactor was observed more often than in other food groups. On the other hand, cofactors were not present in peach- and nut-related reactions. Exercise was the most frequent cofactor in all groups. Conclusion: In our series, the severity of the reactions was not determined by the kind of food or presence of a cofactor. Anaphylactic shock seems to be an infrequent presentation that may be associated with other individual-related factors requiring further evaluation.
Gastrointestinal Symptoms: Under the Tip of the Iceberg in Lipid Transfer Protein Food Allergy
(Esmon Publicidad S.A., 2024-07-30) Ruano Zaragoza, Maria; Araujo Sánchez, Giovanna; Gelis, Sònia; Loli Ausejo, David Enrique; Mir Ihara, Patricia Karina; Mascaró Hereza, Berta; Sánchez Fernández, M.C.; Pascal i Capdevila, Mariona ; Muñoz-Cano, Rosa; Bartra Tomàs, Joan
Gastrointestinal symptoms (GIS) have been reported to be a manifestation of IgE-mediated food allergy (FA), although epidemiologic data are limited. Patients with FA caused by lipid transfer proteins (LTP-FA) may react to many different plant foods, present a broad spectrum of clinical symptoms (ranging from oral allergy syndrome to anaphylaxis), and develop GIS.
Methylation profile scores of environmental exposures and risk of relapse after a first episode of schizophrenia.
(Elsevier B.V., 2025-02-16) González Segura, Àlex; Prohens Coll, Llucia; Julià, Laura; Amoretti Guadall, Silvia; RIbero Rodríguez, Maria; Pino Camacho, Laura; Cano Escalera, Guillermo; Mané, Anna; Rodriguez Jimenez, Roberto; Roldán, Alexandra; Sarró, Salvador; Ibañez, Angela; Usall i Rodié, Judith; Lobo, Antonio; García Rizo, Clemente; Cuesta, Manuel J.; Parellada, Mara; González-Pinto, Ana; Berrocoso, Esther; Bernardo Arroyo, Miquel; Mas Herrero, Sergi; Rodriguez Ferret, Natalia
Both genetic and environmental factors have been found to play a significant role in psychosis relapse, either independently or through their synergistic interaction. Recently, DNA methylation (DNAm) has been proposed through the calculation of methylation profile scores (MPS). The aim of the present study is to evaluate the association of MPS as a surrogate marker of the biological impact of early stressful life events (including stressful intrauterine conditions and obstetric complications, childhood adversity and toxic habits), with the risk of schizophrenia (SCZ) relapse. 91 participants from a cohort of first-episode schizophrenia (FES) patients with less than five years of evolution were classified as non-relapse (patients who had not experienced a relapse after 3 years of enrollment) or relapse (patients who relapsed during the 3-year follow-up). As inclusion criteria, patients fulfilled Andreasen’s criteria of symptomatic remission. Genome-wide DNA methylation (DNAm) was profiled and fourteen MPS reflecting environmental exposure were constructed including both early stressful life events (including stressful intrauterine conditions and delivery issues, childhood adversity) and toxic habits. Increased levels of MPS reflecting gestational diabetes (p = 0.009), hypertensive disorders during pregnancy (p = 0.004), pre-eclampsia (p = 0.049), early preterm birth (p = 0.030), childhood adversity abuse (p = 0.021) and all childhood adversity (p = 0.030) were significantly associated with an increased risk of relapse. Our study suggests that changes in specific methylation patterns may represent one of the biological mechanisms linking early stressful life events to an increased risk of relapse.
Higher seroprevalence of hepatitis E virus in autoimmune hepatitis: Role of false-positive antibodies
(John Wiley & Sons, 2020-03) Llovet, Laura Patricia; Londoño, María Carlota; Gratacós Ginès, Jordi; Ortiz, Oswaldo; Rodriguez Tajes, Sergio; Lens García, Sabela; Reverter, Enric; Ruiz Ortiz, Estíbaliz; Costa Faidella, Jordi; Viñas, Odette; Forns, Xavier; Parés Darnaculleta, Albert
Background and aims Recent studies have found an increase in the seroprevalence of hepatitis E virus (HEV) infection in patients with autoimmune hepatitis (AIH). We aimed to assess the prevalence of positive anti-HEV IgM and IgG, and HEV-RNA in a cohort of patients with AIH, to determine the impact of positive HEV serology on patient outcome, and to evaluate the role of hypergammaglobulinemia and positive autoantibodies in the presence of positive anti-HEV serology. Methods One hundred and five patients tested for HEV infection between 2014 and 2018 were included in the study: 50 with chronic AIH (more than 1 year on treatment), and 55 with an acute hepatitis (30 patients with acute AIH and 25 with non-AIH). Results Seroprevalence of HEV was higher in patients with acute AIH (17% vs 10% in patients with chronic AIH and 8% in patients with non-AIH). Patients with acute AIH and positive anti-HEV IgG were older (58 vs 40; P = .006), had higher IgG levels (27 g/dL vs 13 g/dL; P = .03) and antismooth muscle antibodies (ASMA) titres (1:160 vs 1:80; P = .045), and were more likely to have another autoimmune disease (60% vs 16%; P = .03). At the time of HEV testing, anti-HEV IgG positive patients had significantly higher serum IgG levels (17 g/L vs 11 g/L; P = .009), ANA (1:160 vs 1:60; P = .026) and ASMA titres (1:80 vs 1:40; P = .021). Conclusion Seroprevalence of HEV in patients with AIH in Catalonia does not differ from that of the general population. The higher HEV seroprevalence in patients with acute AIH with higher levels of gammaglobulins and high antibody titres suggest the presence of cross-reactivity between HEV and liver antigens.
Protocol d'estudi prospectiu, unicèntric, doble ceg, randomitzat i Controlat amb Placebo sobre la eficacia d'una dieta baixa en histamina i suplementació amb l'enzima DAO en malalts amb intolerància a la histamina.
(MDPI, 2024-12-25) Combalia, Andrea; Comas Basté, Oriol; Casas Rodríguez, Rosa M.; Latorre Moratalla, Mariluz; Estruch Riba, Ramon; Vidal Carou, Ma. Carmen; Duelo, Adriana; Sánchez Pérez, Sònia; Ruiz León, Ana María; Casanovas Garriga, Francesc; Pellicer Roca, Salvador; Iduriaga-Platero, Irache; Costa-Catala, Judit; Veciana Nogués, María Teresa; Fernández-Solà, J. (Joaquim); Muñoz-Cano, Rosa; Bartra Tomàs, Joan
Background/Objectives: Histamine intolerance is primarily caused by a deficiency in the diamine oxidase (DAO) enzyme at the intestinal level. The reduced histamine degradation in the gut leads to its accumulation in plasma, thereby causing multiple clinical manifestations, such as urticaria, diarrhea, headache, dyspnea, or tachycardia, among others. The dietary management of this food intolerance consists of the follow-up of a low-histamine diet, often combined with DAO supplementation. To date, around twenty studies have investigated the effectiveness of these dietary strategies in reducing the frequency and/or intensity of symptoms, with promising results. However, the limitations of these studies (small patient cohort, lack of control group, and short dietary intervention periods) highlight the need for more ambitiously designed research. Therefore, the main objective of this prospective, unicentric, double-blind, randomized, and placebo-controlled trial is to evaluate the efficacy of a low-histamine diet and/or DAO supplementation over a three-month period in improving symptoms of histamine intolerance. Additionally, the impacts of these dietary strategies on the intestinal microbiota composition, urinary profile of histamine metabolites, serum DAO activity, and plasma histamine levels will be assessed throughout the intervention. Methods: The trial will enroll 400 patients who will be randomly assigned to one of two groups: the intervention group, which will follow a low-histamine diet, or the control group, which will maintain their habitual dietary habits. Within each of these groups, participants will be further divided into four subgroups to receive either exogenous DAO enzyme supplementation (from porcine or plant sources, with the latter administered at two different dosages) or a placebo. Therefore, a total of eight distinct intervention groups will be considered. The comparison of these groups will allow the evaluation of the individual effects of the low-histamine diet or DAO enzyme supplementation, as well as their possible synergistic effect. Results: The results of this study should help to improve dietary recommendations for histamine-intolerant patients and ultimately enhance their quality of life.
Effects of JNJ-46356479 and clozapine on VGLUT1 and GAD65/67 brain levels and expression of genes related to glutamate and GABA in mice postnatally exposed to ketamine.
(Elsevier Masson SAS, 2025-11) Martínez Pinteño, Albert; Olivares-Berjaga, D.; Rodriguez Ferret, Natalia; Mena, Juan Ignacio; Prohens Coll, Llucia; Mas, Sergi; Morén Núñez, Constanza; Parellada Rodón, Eduard; Gassó Astorga, Patricia
Schizophrenia (SZ) is a complex mental disorder influenced by genetic, environmental, and neurobiological factors, with current treatments ineffective for negative symptoms and cognitive deficits. The glutamatergic hypothesis of SZ highlights the N-methyl-D-aspartic acid (NMDA) receptor dysfunction as a key factor, causing excitatory-inhibitory imbalance and synaptic inefficiency. Positive allosteric modulators (PAMs) of the metabotropic glutamate receptor 2 (mGluR2), such as JNJ-46356479 (JNJ), could be useful in treating these symptoms, especially when used in early stages of the disease. Previous results have shown that JNJ can reverse certain SZ-related behavioral and neuropathological deficits. This study evaluates, for the first time, the effects of early treatment with JNJ or clozapine (CLZ) in reversing molecular deficits related to glutamatergic and GABAergic pathways in mice postnataly exposed to ketamine (KET) on postnatal days (PND) 7, 9, and 11. Animals received JNJ or CLZ daily in the adolescent period (PND 35–60). Specifically, we investigated alterations in brain protein levels of VGLUT1, as a marker of glutamatergic synapses, and GAD65/67, as markers of GABAergic synapses. Changes in brain expression of 240 selected genes involved in glutamate and GABA pathways were also evaluated. Results demonstrated that postnatal KET exposure increased hippocampal VGLUT1 levels which were partially normalized after both pharmacological treatments, especially with JNJ. Additionally, we identified some genes that showed altered brain expression after drug treatment in our mouse model. In conclusion, this study provides evidence of SZ-related glutamate signaling alterations in adult mice postnatally exposed to KET, as well as of the effectiveness of JNJ in improving these alterations when administered during the early stages of the disease.
Mitochondrial Oxidative Phosphorylation System Dysfunction in Schizophrenia.
(MDPI, 2025-05-06) Morén Núñez, Constanza; Olivares Berjaga, David; Martínez Pinteño, Albert; Bioque Alcázar, Miquel; Rodriguez Ferret, Natalia; Gassó Astorga, Patricia; Martorell, Lourdes; Parellada Rodón, Eduard
Schizophrenia (SCZ) is a severe, chronic mental disorder of unknown etiology and limited therapeutic options. Bioenergetic deficits in the oxidative phosphorylation system (OXPHOS) during early postnatal brain development may underlie disrupted neuronal metabolism and synaptic signaling, contributing to the neurodevelopmental and behavioral disturbances observed in patients. This narrative review summarizes updated evidence linking mitochondrial-OXPHOS dysfunction to SCZ pathophysiology. The novelty lies in the focus on OXPHOS dysfunction at the enzymatic/functional level, rather than on genetic, transcriptional, or oxidative parameters. While complex I impairment has long been highlighted and proposed as a peripheral marker of the disease, recent studies also report alterations in other OXPHOS complexes and their precursors. These findings suggest that OXPHOS dysfunction is not isolated to a single enzymatic component but affects broader mitochondrial function, alongside oxidative stress, contributing to disease progression through mechanisms involving apoptosis, accelerated aging, and synaptic deterioration. OXPHOS dysfunction in both central and peripheral tissues further supports its relevance to SCZ. Overall, the literature points to mitochondrial OXPHOS abnormalities as a significant biological feature of SCZ. Whether these alterations are causal factors or consequences of disease processes remains unclear. Understanding OXPHOS dysregulation may open new avenues for targeted therapies.
Effectiveness of positive allosteric modulators of metabotropic glutamate receptor 2/3 (mGluR2/3) in animal models of schizophrenia.
(Nature Publishing Group, 2025-01-14) Olivares Berjaga, David; Martínez Pinteño, Albert; Rodriguez Ferret, Natalia; Mas Herrero, Sergi; Morén Núñez, Constanza; Parellada Rodón, Eduard; Gassó Astorga, Patricia
Schizophrenia (SZ) is a deleterious brain disorder characterised by its heterogeneity and complex symptomatology consisting of positive, negative and cognitive deficits. Current antipsychotic drugs ameliorate the positive symptomatology, but are inefficient in treating the negative symptomatology and cognitive deficits. The neurodevelopmental glutamate hypothesis of SZ has opened new avenues in the development of drugs targeting the glutamatergic system. One of these new therapies involves the positive allosteric modulators (PAMs) of metabotropic glutamate receptors, mainly types 2/3 (mGluR2/3). mGluR2/3 PAMs are selective for the receptor, present high tolerability and can modulate the activity of the receptor for long periods. There is not much research in clinical trials regarding mGluR2/3 PAMs. However, several lines of evidence from animal models have indicated the efficiency of mGluR2/3 PAMs. In this review, focusing on in vivo animal studies, we will specifically discuss the utilization of SZ animal models and the various methods employed to assess animal behaviour before summarising the evidence obtained to date in the field of mGluR2/3 PAMs. By doing so, we aim to deepen our understanding of the underlying mechanisms and the potential efficiency of mGluR2/3 PAMs in treating SZ. Overall, mGluR2/3 PAMs have demonstrated efficiency in attenuating SZ-like behavioural and molecular deficits in animal models and could be useful for the early management of the disorder or to treat specific subsets of patients.
Time to Diagnosis and Presenting Symptoms of Patients Diagnosed With Cancer Through Emergency and Nonemergency Routes: A Large Retrospective Study From a High-Volume Center
(American Society of Clinical Oncology, 2024-03-08) Bosch Genover, Xavier; Mota Gomes, Tiago; Montori Palacín, Elisabet; Moreno Lozano, Pedro Juan; López-Soto, Alfonso
Purpose The symptoms with which a patient with cancer presents and the route taken to diagnosis (emergency v nonemergency) may affect the speed with which the diagnosis of cancer is made, thereby affecting outcomes. We examined time to diagnosis by symptom for cancers diagnosed through emergency and nonemergency routes (NERs). Methods We performed a retrospective review of patients diagnosed with 10 solid cancers at Hospital Clínic of Barcelona between March 2013 and June 2023. Cancers were diagnosed through emergency presentation and admission (inpatient emergency route [IER]), emergency presentation and outpatient referral (outpatient emergency route [OER]), and primary care presentation and outpatient referral (NER). We assessed the effect of diagnostic routes on intervals to diagnosis for 19 cancer symptoms. Results A total of 5,174 and 1,607 patients were diagnosed with cancer through emergency routes and NERs, respectively. Over 85% of patients presenting with alarm (localizing) symptoms such as hematuria through emergency routes were diagnosed with the expected cancer, whereas those with nonlocalizing symptoms such as abdominal pain had a more heterogeneous cancer-site composition. Median intervals were shorter for alarm than nonlocalizing symptoms and tended to be shorter in IERs than OERs. However, for most symptoms, intervals in both routes were invariably shorter than in the NER. For example, diagnostic intervals for hematuria and abdominal pain were 3 and 5 days shorter in IERs than OERs, but they were 5-8 and 17-22 days shorter than in the NER, respectively. Conclusion For patients with alarm symptoms, intervals were shorter than for those with nonlocalizing symptoms and, for most symptoms, intervals were shorter when patients were evaluated by emergency routes rather than NERs.
Time intervals and previous primary care consultations in the pathway to emergency cancer diagnosis
(Elsevier, 2023-10-01) Bosch Genover, Xavier; Montori Palacín, Elisabet; Calvo Jiménez, Júlia; Carbonell, Irene; Naval Álvarez, José; Moreno Lozano, Pedro Juan; López-Soto, Alfonso
Background: Time intervals and number of prior consultations in primary care (PC) are recognised metrics of diagnostic timeliness of cancer and are interrelated. However, whether and how the two measures correlate with each other in the emergency diagnostic pathway is unknown. We investigated the association between the number of prereferral consultations and the length of intervals from PC presentation to cancer diagnosis following emergency referral to hospital. Methods: Patients were eligible if they first consulted in PC and were diagnosed with cancer following emergency or nonemergency referral to hospital. We analysed for differences in PC and diagnostic intervals and number of consultations between emergency and nonemergency presenters and determined their associations by cancer type. Differences in presenting symptoms and stage at diagnosis between populations and according to number of consultations were also examined. Results: There were 796 emergency and 865 nonemergency presenters with comparable sociodemographic and comorbidity data. Correlation analysis in emergency presenters revealed a strong positive association between number of consultations and intervals for seven of 13 different cancers, including cancers characterised by high proportions of > 3 consultations and long intervals (pancreatic, lung, and colorectal cancer) and vice versa for others (e.g., endometrial, cervical, or oesophageal cancer). Additionally, emergency presenters with > 3 consultations were more likely than those with 1-2 to report nonspecific symptoms (60 vs. 40%, respectively) and to be diagnosed at a later stage. Conclusion: System level interventions are needed to reduce unnecessary delays in the emergency diagnostic pathway, particularly in cancer patients with multiple prereferral consultations. The findings also suggest opportunities to reduce the proportion of emergency diagnoses by targeting symptomatic individuals pre-presentation.
Time intervals in the pathway to emergency cancer diagnosis.
(Taylor & Francis, 2023) Bosch Genover, Xavier; Montori Palacín, Elisabet; Naval Álvarez, José; Matas García, Ana; Moreno Lozano, Pedro Juan; López-Soto, Alfonso
Aim: Evidence on time-based metrics for cancers diagnosed through emergency presentation is lacking. We examined the duration of intervals from first symptoms to cancer diagnosis in the emergency versus primary care (PC) presentation route. Methods: Retrospective study of outpatients diagnosed with 15 solid cancers over 5 years. The outcome was the length of prediagnostic intervals by diagnostic route. Results: Median intervals in emergency presenters (n = 3167) were shorter than in PC presenters (n = 2215). However, intervals in emergency presenters with three or more prior PC consultations were similar to PC but remarkably longer than in those with one or two and no consultations. Conclusion: As we provide new interval measures for the emergency diagnostic pathway, results highlight the contribution of prior consultations to interval lengths.
Prognostic risk and survival of asymptomatic IgM monoclonal gammopathy: Results from a Spanish Multicenter Registry
(Wolters Kluwer, 2024-11-12) Moreno Fajardo, David; Jiménez, Cristina; Escalante, Fernando; Askari, Elham; Castellanos Alonso, Marta; Arnao, Mario; Heredia, Ángela; Canales Albendea, Miguel Ángel; Alcalá, Magdalena; Bermúdez, Arancha; Saus Carreres, Ana; Casanova, María; Palomera Bernal, Luis; Motlló, Cristina; Garcia Sánchez, Ricarda; Rios Rull, P.J.; García Sanz, Ramón; Fernández de Larrea, Carlos
Asymptomatic IgM gammopathy encompasses IgM monoclonal gammopathy of undetermined significance (MGUS) and asymptomatic Waldenström macroglobulinemia (AWM), both having a risk of progression to symptomatic disease. Here, we assessed the risk of progression and the mortality of 956 patients with asymptomatic IgM gammopathy across 25 Spanish centers. After a median follow-up of 5.7 years, 156 patients progressed, most of them to symptomatic WM (SWM). The cumulative incidence of progression was 13% and 20% at 5 and 10 years, respectively. The serum IgM ≥10 g/L, bone marrow (BM) infiltration ≥20%, β2-microglobulin ≥3 mg/L, and albumin <4 g/dL were the most potent predictors of disease progression in a multivariate Cox regression model, allowing the identification of three risk categories. The probability of progression to symptomatic disease at 5 years was 4.5%, 15.7%, and 42.8% for low-, intermediate-, and high-risk groups, respectively. In patients without a BM evaluation, the presence of none or 1 risk factor and 2 or 3 risk factors conferred a progression risk of 6% and 27% at 5 years, respectively. The model was independent of the presence of MYD88 L265P, which conferred a negative impact only in AWM patients. The relative survival (RS) ratio at 5 years of asymptomatic patients was similar to the Spanish population, which contrasted with the 0.76 5-year RS of SWM patients. Overall, the Spanish Multicenter Model comprehensively describes the risk of progression of asymptomatic patients and shows that the excess mortality is increased only in the symptomatic stage of the disease.
Genomic and immune profiling of prognostic risk groups in IgM gammopathy reveals novel biomarkers beyond MYD88 L265P
(Frontiers Media, 2025-07-01) Moreno, David F.; Nadeu Prat, Ferran; Brasó Maristany, Fara; Vaqué, Sergi; Paz, Sara; Mañé Pujol, Joan; Cardús, Oriol; Medina, Elena; Lozano, Ester; Rodríguez Lobato, Luis Gerardo; Daniel, Anna de; Tovar, Natalia; Cibeira, María Teresa; Bladé, J. (Joan); Rosiñol Dachs, Laura; Colomer Pujol, Dolors; Prat Aparicio, Aleix; Fernández de Larrea, Carlos
Background: MYD88 L265P is an early mutation in IgM monoclonal gammopathy of undetermined significance (MGUS) and asymptomatic Waldenström macroglobulinemia (WM). Given the high prevalence of the MYD88 mutation observed in epidemiological studies, its presence is not sufficient to drive disease progression. In fact, a recent risk model of progression reported that the impact of other laboratory biomarkers was superior to the MYD88 mutation's presence. Due to the low incidence of these clinicopathological entities, there is a need for a better characterization of tumor and immune cells that can help to identify novel biomarkers. We hypothesize that the characterization of the risk groups in asymptomatic patients could improve the discovery of drivers of disease progression. Methods: We characterized the genomic and immune landscape of the most recent prognostic risk categories in 19 IgM MGUS and 17 asymptomatic WM patients. We performed targeted next generation sequencing (NGS) on CD19+ cells from bone marrow samples at diagnosis using a panel of 54 lymphoma-driver genes. Whole bone marrow samples were also used to measure mRNA gene expression in tumor and immune cells using the PanCancer ImmuneProfiling panel on the nCounter platform (NanoString). Results: We observed that low-risk patients were only characterized by the presence of MYD88 L265P, while intermediate- and high-risk groups harbored additional mutations on CXCR4, KMT2D, ARID1A and EP300. Regarding the mRNA expression analyses, we found an increased proportion of myeloid cells in the low-risk group, with monocytes having a significant decrease in low versus high-risk patients. The high-risk group also upregulated genes involved in the activation of NF-κB and B-cell receptor (BCR) signaling, while low-risk patients upregulated genes associated with an alternative activation of B cells or a decrease of the BCR signaling, such as TOLLIP, CEACAM1 and CR1. Conclusions: Beyond the MYD88 mutation, we described novel molecular mechanisms associated with high-risk patients, as an effort moving towards easy-to use new biomarkers in IgM gammopathy.
Sleep–wake variations of electrodermal activity in bipolar disorder
(John Wiley & Sons, 2024-06-18) Valenzuela-Pascual, Clàudia; Mas, Ariadna; Borràs, Roger; Anmella, Gerard; Sanabra González, Miriam; González Campos, Meritxell; Valentí Ribas, Marc; Pacchiarotti, Isabella; Benabarre, Antonio; Grande i Fullana, Iria; De Prisco, Michele; Oliva, Vincenzo; Bastidas Salvadó, Anna; Agasi, Isabel; Young, Allan H.; Garriga, Marina; Murru, Andrea; Corponi, Filippo; Li, Bryan M.; Looff, Peter de; Vieta i Pascual, Eduard, 1963-; Hidalgo Mazzei, Diego
Background: Affective states influence the sympathetic nervous system, inducing variations in electrodermal activity (EDA), however, EDA association with bipolar disorder (BD) remains uncertain in real-world settings due to confounders like physical activity and temperature. We analysed EDA separately during sleep and wakefulness due to varying confounders and potential differences in mood state discrimination capacities. Methods: We monitored EDA from 102 participants with BD including 35 manic, 29 depressive, 38 euthymic patients, and 38 healthy controls (HC), for 48 h. Fifteen EDA features were inferred by mixed-effect models for repeated measures considering sleep state, group and covariates. Results: Thirteen EDA feature models were significantly influenced by sleep state, notably including phasic peaks (p < 0.001). During wakefulness, phasic peaks showed different values for mania (M [SD] = 6.49 [5.74, 7.23]), euthymia (5.89 [4.83, 6.94]), HC (3.04 [1.65, 4.42]), and depression (3.00 [2.07, 3.92]). Four phasic features during wakefulness better discriminated between HC and mania or euthymia, and between depression and euthymia or mania, compared to sleep. Mixed symptoms, average skin temperature, and anticholinergic medication affected the models, while sex and age did not. Conclusion: EDA measured from awake recordings better distinguished between BD states than sleep recordings, when controlled by confounders.
Autoantibodies are associated with worse outcomes in MASLD
(Elsevier, 2025-10-01) Soria, Anna; Diaz Lorca, Maria Alba; Iruzubieta, Paula; Martín Mateos, Rosa; Salcedo Allende, María Teresa; Jiménez Masip, Alba; Fuster Anglada, Clara; Arias Loste, Maria Teresa; Perna, Cristina; Maimouni, Cautar el; Pericàs, Juan M.; Ferrer Gómez, Ana; Jiménez González, Carolina; Muñoz Martínez, Sergio; Padilla, Marlene; Crespo, Javier; Calixto, Zyanya; Sabiote, Clara; Albillos, Agustín; Cervera Carbonell, Marta; Olivas, Ignasi; Arvaniti, Pinelopi; Hernández Évole, Helena; Jiménez Esquivel, Natalia; Gratacós-Ginès, Jordi; Juanola, Adrià; Pose Méndez, Elisa; Coll, Mar; Nadal, Ruth; Pérez-Guasch, Martina; Fabrellas i Padrès, Núria; Ginès, Pere; Londoño, María Carlota; Graupera, Isabel
Background & Aims Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease worldwide. Autoantibodies (Ab), such as antinuclear antibodies (ANA) and anti-smooth muscle antibodies (ASMA), are frequently detected in MASLD, but their role in disease progression remains controversial. This study aimed to evaluate the prevalence of positive Ab and the histological features of autoimmune hepatitis (AIH) in MASLD and their association with liver-related outcomes. Methods We conducted a multicenter, retrospective, longitudinal study of patients with biopsy-proven MASLD from the HEPAmet Registry. Data on ANA (≥1/80), ASMA (≥1/40), and AIH histological features (portal inflammation, interface hepatitis, and plasma cell infiltration) were analyzed for their association with compensated advanced chronic liver disease (cACLD), liver decompensation, and death. Results Of the 460 patients (49% women, median age 58 years, median BMI 33 kg/m2, and 45% with advanced fibrosis), 17% and 25% tested positive for ANA and ASMA, respectively. Histological features of AIH included interface hepatitis (19%), moderate/severe portal inflammation (12%), and plasma cell clusters (10%). Possible AIH based on histological criteria was present in 8% of patients. The presence of positive Ab was independently associated with cACLD development (odds ratio 2.890, p <0.030), liver decompensation (hazard ratio 3.969, p = 0.001), and death (hazard ratio 2.546, p = 0.036). In contrast, the presence of isolated histologic autoimmune features was not correlated with serological markers and did not affect the prognosis of MASLD. Conclusions ANA and ASMA are commonly found in patients with MASLD and are associated with poorer liver-related outcomes and reduced survival, whereas isolated histological autoimmune features provide no additional prognostic value. Impact and implications Metabolic dysfunction-associated steatotic liver disease (MASLD) can coexist with other liver diseases, including autoimmune hepatitis. The role of autoantibodies and histological autoimmune features in MASLD progression remains controversial. Understanding the relationship between autoimmune characteristics and disease progression in MASLD may help physicians identify high-risk populations, enhance risk stratification, and personalize disease treatment.
A cross-sectional pilot study to define anal cancer risk factors in HIV-positive solid organ transplant recipients.
(Taylor & Francis, 2025-11-14) Fuertes, Irene; Chivite, Ivan; Cranston, R.D.; Sánchez, Emilia; Lazzari, Elisa de; Marimon, Lorena; Ordi i Majà, Jaume; Miró Meda, José M. (José María), 1956-; Blanco, José L.
Background HIV-positive organ transplant recipients are at high risk of anal cancer, but there are no data on the prevalence of high-risk human papillomavirus (hr-HPV) or anal dysplasia, in this population. Objective To assess the prevalence of anal hr-HPV, and anal cytological and histological abnormalities in this population. Design and setting Prospective single tertiary hospital. Results Twenty-five (53%) transplant recipients were recruited from 47 eligible individuals. Median (IQR) age was 56 years (52.5–60), 17 were male, 9 (36%) were men who have sex with men and 8 (32%) were active smokers. Twelve (48%) patients had abnormal anal cytology and 12 (48%) had detectable hr-HPV DNA. Six (50%) individuals with abnormal cytology had high-grade squamous intraepithelial lesions (HSIL) on biopsy. Abnormal anal cytology was significantly associated with current hr-HPV infection [crude prevalence rate ratio, cRR = 2.3, 95% CI (1.43–3.7); p = 0.001] and any previous history of HPV associated disease [cRR = 2.49, 95% CI (1.09–5.67); p = 0.030]. Anal HSIL on biopsy was associated with presence of condyloma [cRR = 3.00, 95% CI (1.31–6.88); p = 0.001] and any previous history of any HPV associated disease [cRR = 6.67, 95% CI (0.96–46.32); p = 0.055]. Anal hr-HPV infection was associated with any previous HPV disease (Crude risk ratios [cRR = 2.89, 95% CI (1.21–6.88); p = 0.017]) and presence of condyloma (Crude risk ratios [cRR = 2.00, 95% CI (1.28–3.13); p = 0.002]). No cases of invasive anal cancer were detected among study participants. Conclusions This highly medicalized population of HIV-positive organ transplant recipients have a high prevalence of HPV-associated anal dysplasia and screening to prevent anal cancer may need to be prioritised.
Characteristics and outcome of acute heart failure in infective endocarditis: focus on cardiogenic shock.
(Oxford University Press, 2021-09-07) Pericàs, Juan M.; Hernández Meneses, Marta; Muñoz, Patricia; Martínez Sellés, Manuel; Álvarez Uria, Ana; Alarcón, Aristides de; Gutiérrez Carretero, Encarnación; Goenaga Sánchez, Miguel Ángel; Zarauza Navarro, Manuel Jesús; Falces Salvador, Carles; Rodríguez Esteban, María Ángeles; Hidalgo Tenorio, Carmen; Hernández Cabrera, Michele; Miró Meda, José M.; Spanish Collaboration on Endocarditis—Grupo de Apoyo al Manejo de la Endocarditis Infecciosa en España (GAMES)
Background: Studies investigating the impact of cardiogenic shock (CS) on endocarditis are lacking. Methods: Prospectively collected cohort from 35 Spanish centers (2008-2018). Logistic regression analyses were performed to identify risk factors for developing CS and predictors of mortality. Results: Among 4856 endocarditis patients, 1652 (34%) had acute heart failure (AHF) and 244 (5%) CS. Compared with patients without AHF and AHF but no CS, patients with CS presented higher rates of surgery (40.5%, 52.5%, and 68%; P < .001) and in-hospital mortality (16.3%, 39.1%, and 52.5%). Compared with patients with septic shock, CS patients presented higher rates of surgery (42.5% vs 68%; P < .001) and lower rates of in-hospital and 1-year mortality (62.3% vs 52.5%, P = .008, and 65.3% vs 57.4%, P = .030). Severe aortic and mitral regurgitation (OR [95% CI], 2.47 [1.82-3.35] and 3.03 [2.26-4.07]; both P < .001), left-ventricle ejection fraction <60% (1.72; 1.22-2.40; P = .002), heart block (2.22; 1.41-3.47; P = .001), tachyarrhythmias (5.07; 3.13-8.19; P < .001), and acute kidney failure (2.29; 1.73-3.03; P < .001) were associated with higher likelihood of developing CS. Prosthetic endocarditis (2.03; 1.06 -3.88; P = .032), Staphylococcus aureus (3.10; 1.16 -8.30; P = .024), tachyarrhythmias (3.09; 1.50-10.13; P = .005), and not performing cardiac surgery (11.40; 4.83-26.90; P < .001) were associated with a higher risk of mortality. Conclusions: AHF is common among patients with endocarditis. CS is associated with high mortality and should be promptly identified and assessed for cardiac surgery. Trial registration: ClinicalTrials.gov NCT00871104.
Polygenic risk score of glycemic homeostasis, Type 2 Diabetes Mellitus and glycemic components in first episode psychosis
(Elsevier B.V., 2025-11-01) Segura, Alex G.; Verdolini, Norma; Valli, Isabel; García Rizo, Clemente; Diaz-Caneja, Covadonga M.; Vieta i Pascual, Eduard, 1963-; Mezquida Mateos, Gisela; Lobo, Antonio; González-Pinto, Ana; Andreu-Bernabeu, Álvaro; Roldán, Alexandra; Martínez-Arán, Anabel, 1971-; Baeza, Inmaculada, 1970-; Mane, Anna; Labad, Javier; Müller, Daniel J.; Guasch-Capella, Nora; Bernardo Arroyo, Miquel; Mas Herrero, Sergi; Bioque Alcázar, Miquel; González, Jairo; Andrés, Pablo; Cavone, Vito; Corripio, Iluminada; Duque, Alejandra; Mar Barrutia, Lorea; Marin, Julen; De-la-Camara, Concepción; Vaquero-Puyuelo, David; Rivero, Olga; Escartí Fabra, María José; Trabsa, Amira; Legido, Teresa; Forte, Maria Florencia; Serra Navarro, Maria; de la Serna, Helena; Castro-Fornielles, J.; Contreras, Fernando; García-Portilla González, María Paz, 1962-; González-Blanco, Leticia; Segarra Echevarría, Rafael; Zabala Rabadán, Arantzazu; Rodríguez-Jiménez, Roberto; Martínez-Gras, Isabel; Usall i Rodié, Judith; Barajas, Ana; Sarró, Salvador; Pomarol-Clotet, Edith; Ibañez, Angela; Cuesta, Manuel J.
Objective: First episode of psychosis (FEP) is associated with glucose homeostasis abnormalities even before pharmacological intervention. Given inconclusive GWAS results regarding a direct genetic link between schizophrenia and type 2 diabetes mellitus (T2DM), we hypothesized that FEP patients may exhibit altered genetic risk for glycemic traits. We compared polygenic risk scores (PRS) for T2DM (PRST2DM), fasting glucose (PRSFG), and glycated hemoglobin (HbA1c) (PRSHbA1c) between FEP patients and controls, examining their associations with glycemic measures over 24 months. Methods: We analyzed data from 242 FEP patients and 119 controls, assessing fasting serum glucose and HbA1c at baseline and 24 months. We examined cross-sectional and longitudinal associations between PRS and glycemic measures within each group. Results: FEP patients and controls did not differ significantly in PRS. Significant associations were observed for PRSFG with baseline serum glucose in controls (p = 0.008), PRSFG during follow-up (p = 0.034), PRSHbA1c at 24 months (p = 0.018), and HbA1c longitudinally (p = 0.025). After multiple testing corrections, only the association between PRSFG and baseline serum glucose in controls remained significant (p_adj = 0.023). No associations were found for PRST2DM. Conclusions: Despite the link between FEP and glycemic disturbances, PRST2DM did not differ between FEP patients and controls. However, PRS for glycemic traits showed associations with glycemic measures in both groups before multiple testing correction, suggesting that genetic predisposition may influence glucose homeostasis in early psychosis. The absence of a direct association between common genetic variants underlying T2DM and early glycemic dysregulation in FEP underscores the importance of considering environmental factors and epigenetic mechanisms.

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