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    Preterm prelabor rupture of membranes: the use of amniocentesis to detect intraamniotic infection reduces maternal and neonatal duration of antibiotic exposure
    (Elsevier, 2025-11-01) Cobo Cobo, Maria Teresa; Aldecoa Bilbao, Victoria; Ferrero Martinez, Sílvia ; Balcells, Judith; Contreras, Ana Lucia; Valenzuela Rodríguez, Andrea; Pastor Lorca, María; Boada, David; Herranz Barbero, Ana; Izquierdo Renau, Montserrat; Murillo Bravo, Clara; Río, Ana del; Hernández Meneses, Marta; Fidalgo, Berta; Rodriguez Reyes, Montserrat; Figueras Retuerta, Francesc; Gratacós Solsona, Eduard; Palacio, Montse
    Current management guidelines for patients with preterm prelabor rupture of membranes at <32þ0 weeks of gestation recommend administering antibiotics, although evidence on their benefits for short- and long-term neonatal outcomes is poor. OBJECTIVE: This study aimed to evaluate whether the use of amniocentesis to detect intraamniotic infection reduces maternal and neonatal duration of antibiotic exposure. STUDY DESIGN: This was a retrospective observational cohort study (2014e2023) including patients diagnosed with preterm prelabor rupture of membranes at <32þ0 weeks of gestation who underwent amniocentesis at admission to assess the presence of intraamniotic infection. We compared 2 groups according to antenatal antibiotic management. From 2014 to 2019, patients received at least 5 days of broad-spectrum antibiotic treatment (including intravenous ampicillin and gentamicin and a single dose of oral azithromycin), regardless of intraamniotic infection status (standard management group). Beyond 2019, gentamicin was substituted for intravenous ceftriaxone and azithromycin for oral clarithromycin. Antibiotic treatment duration was optimized on the basis of amniotic fluid analysis (amniocentesis-based management): if amniotic fluid glucose concentrations were 14 mg/dL and Gram staining did not show the presence of bacteria, antibiotic treatment was discontinued at 48 hours. Otherwise, antibiotic therapy was prolonged at least until microbiological amniotic fluid results. Regardless of the management group, if intraamniotic infection was diagnosed, the type of antibiotic was individualized according to the bacteria isolated, and treatment was prolonged for 7 to 10 days unless delivery occurred earlier. There were no other differences in maternal management between the 2 periods. RESULTS: A total of 172 patients diagnosed with preterm prelabor rupture of membranes at <32þ0 weeks of gestation were included (122 in the standard management group and 50 in the amniocentesis-based management group). The prevalence of intraamniotic infection was 29% in both periods, with most cases (61%) being due to Ureaplasma species. There were no differences in maternal characteristics between the 2 groups. As expected, in the amniocentesis-based management group, maternal exposure to antibiotics was shorter (median [25th centilee75th centile] of 2 [2e3] days [amniocentesis-based management] vs 5 days [4e5] [standard management]; P<.0001). In line with the reduction of the duration of antibiotic therapy, we observed that maternal hospital stay was significantly shorter (5 [4e9] vs 11 [5e21] days; P¼.001) and outpatient management was more frequent (68% vs 47%; P¼.011) in the amniocentesis-based management group. No differences were observed in maternal morbidity. Similar results were found when neonatal outcomes were evaluated. In the amniocentesis-based management group, neonates received less antibiotic treatment at admission (odds ratio [95% confidence interval], 0.31 [0.15e0.61]; P<.001) and had less exposure to antibiotics during hospitalization (614 vs 1318 days in the standard management group; P¼.023). This did not translate into worse neonatal outcomes. CONCLUSION: Management of preterm prelabor rupture of membranes based on amniotic fluid analysis was associated with shorter maternal and neonatal antibiotic exposure and shorter maternal length of hospitalization, and allowed outpatient management without jeopardizing maternal or neonatal outcomes
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    Real-world use of terlipressin in cirrhosis and acute kidney injury: frequent use beyond hepatorenal syndrome
    (Elsevier, 2026-04) Ma, Ann T.; Juanola Mayos, Adrià; Patidar, Kavish R.; Barone, Anna; Incicco, Simone; Kulkarni, Anand V.; Verma, Nipun; Lange, Christian Markus; Xie, Qing; Alessandria, Carlo; Cerda, Eira; Maiwall, Rakhi; Kim, Jeong Han; Marciano, Sebastián; Queiroz Farias, Alberto; Toledo, Claudio; Nardelli, Silvia; Vorobioff, Julio D.; Roblero, Juan Pablo; Thevenot, Thierry; Papp, Maria; Maan, Raoel; Solé, Cristina; Cordova Gallardo, Jacqueline; Simonetto, Douglas A.; Fouad, Yasser; Balcar, Lorenz; Raevens, Sarah; Nabilou, Puria; Merli, Manuela; Presa, José; Laleman, Wim; Krag, Aleksander; Bruns, Tony; Pereira, Gustavo; Mattos, Angelo Z.; Arab, Juan Pablo; Wentworth, Brian; Abdelaaty Abdelkader, Nadia; Wong, Yu Jun; Kim, Sung Eun; Roux, Olivier; Takkenberg, R. Bart; Galante, Antonio; Lofego Goncalves, Luciana; Pyrsopoulos, Nikolaos; Caraceni, Paolo; Pérez Hernández, José Luís; Asrani, Sumeet K.; Torre, Aldo; Díaz Ferrer, Javier; Orman, Eric S.; Perricone, Giovanni; Gadano, Adrian; Ivashkin, Vladimir; Fassio, Eduardo; Marino, Mónica; Vargas, Víctor; Rabinowich, Liane; Montes, Pedro; Mohammed, Abdulsemed; Carrera, Enrique; Cabrera, María Cecilia; Girala, Marcos; Samant, Hrishikesh; Madaleno, Joao; Kim, W. Ray; Ferreira, Carlos Noronha; Allegretti, Andrew S.; Sarin, Shiv K.; Ginès i Gibert, Pere; Angeli, Paolo; Solà, Elsa; Piano, Salvatore; International Club of Ascites GLOBAL AKI team
    Background & Aims Terlipressin is indicated to treat hepatorenal syndrome (HRS)-acute kidney injury (AKI) but is likely used outside this primary indication in clinical practice. We aimed to investigate real-world practice patterns on the use of terlipressin in AKI in cirrhosis. Methods International prospective study including patients hospitalized for decompensated cirrhosis. This was a subgroup analysis of patients who received terlipressin to treat AKI. Primary outcome was AKI resolution. Secondary outcomes were respiratory failure and 28-day mortality. Results Among 1456 patients with AKI, 243 (17%) received terlipressin. Terlipressin was predominantly administered as a continuous infusion (75%). The AKI phenotype was HRS-AKI in 50%, acute tubular necrosis (ATN) in 17%, hypovolemic in 25%, and other in 8%. AKI resolution occurred in 49% of the patients, and was lowest in ATN (29%), followed by HRS-AKI (51%) and hypovolemic (63%). ATN was independently associated with lack of AKI resolution (odds ratio, 2.77; 95% confidence interval, 1.24–6.54; P = .02). De novo respiratory failure occurred in 20% of patients. There were no significant differences in the amount of albumin received nor acute-on-chronic liver failure grade between those who did and did not develop respiratory failure. The presence of pneumonia independently predicted respiratory failure (odds ratio, 7.80; 95% confidence interval, 2.43–26.95; P < .001). Mortality rate at 28 days was 36%; ATN and hospital-acquired AKI independently predicted 28-day mortality. Conclusions Terlipressin is often used for treatment of AKI outside its primary indication of HRS-AKI. Compared with patients with HRS-AKI, response to terlipressin is significantly lower in patients with ATN, in whom the risks may outweigh the benefits. Respiratory failure is common but does not seem to be driven by the amount of albumin received nor acute-on-chronic liver failure grade.
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    Determinants of Intention to Use HIV Pre-exposure Prophylaxis and Condom Use Among a Sample of Cisgender Female Sex Workers Working Mostly Outdoors in Madrid, Spain
    (Springer Verlag, 2024-06-10) Vazquez Guillamet, Laia J.; Valencia, Jorge; Ryan, Pablo; Cuevas Tascón, Guillermo; Del Olmo Morales, Miguel Angel; Cobo, Inés; Lazarus, Jeffrey V.; Chevance, Guillaume
    There is scant knowledge regarding pre-exposure prophylaxis (PrEP) use among female sex workers (FSWs) in Europe. Spain recognized FSWs as a population at high risk of acquiring HIV and granted them subsidized access to PrEP when the medication first became nationally available in 2019. Nevertheless, FSWs represented just 0.2% of PrEP users in 2022. A total of 102 HIV-negative FSWs reached through field activities of local NGOs located in Madrid were interviewed between January and March 2022. Participants were selected through convenience sampling over a fixed recruitment period. FSWs completed a 73-item survey with questions about individual, occupational, social, and structural determinants. The objective of this study was to identify (1) the prevalence of intention to use oral PrEP and its determinants, and (2) the prevalence of inconsistent condom use, which is the risk factor that qualifies FSWs for subsidized PrEP in the national health system, and its determinants. Importantly, the study sample overrepresented street-based FSWs (71.6%). A quarter (25.5%) of the study participants used condoms inconsistently. PrEP awareness was low (9.8%), but intention to use PrEP was high (72.5%). Intention to use oral PrEP was significantly associated with feeling protected against HIV by taking PrEP and perceiving insufficient protection by condom use alone. Inconsistent condom use was significantly associated with frequent heroin/cocaine use, having clients who inject drugs, and willingness to take PrEP despite it not protecting 100% against HIV infection. FSWs, in this specific sample, are likely to benefit from targeted PrEP awareness campaigns and implementation projects that prioritize those who use drugs and are more likely to engage in condomless sex.
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    Report of three azole-resistant Aspergillus fumigatus cases with TR34/L98H mutation in hematological patients in Barcelona; Spain.
    (Springer Verlag, 2024-05-27) Monzó Gallo, Patricia; Alastruey Izquierdo, Ana; Chumbita, Mariana; Aiello, Tommaso Francesco; Gallardo Pizarro, Antonio; Peyrony, Olivier; Teijon Lumbreras, Christian; Alcázar Fuoli, Laura; Espasa, Mateu; Soriano Viladomiu, Alex; Marco Reverté, Francesc; García Vidal, Carolina
    Objectives We aimed to report the emergence of azole-resistant invasive aspergillosis in hematologic patients admitted to a tertiary hospital in Spain during the last 4 months. Methods Prospective, descriptive study was performed to describe and follow all consecutive proven and probable invasive aspergillosis resistant to azoles from hematological cohort during the last 4 months. All patients had fungal cultures and antifungal susceptibility or real-time PCR detection for Aspergillus species and real-time PCR detection for azole-resistant mutation. Results Four cases of invasive aspergillosis were diagnosed in 4 months. Three of them had azole-resistant aspergillosis. Microbiological diagnosis was achieved in three cases by means of fungal culture isolation and subsequent antifungal susceptibility whereas one case was diagnosed by PCR-based aspergillus and azole resistance detection. All the azole-resistant aspergillosis presented TR34/L98H mutation. Patients with azole-resistant aspergillosis had different hematologic diseases: multiple myeloma, lymphoblastic acute leukemia, and angioimmunoblastic T lymphoma. Regarding risk factors, one had prolonged neutropenia, two had corticosteroids, and two had viral co-infection. Two of the patients developed aspergillosis under treatment with azoles. Conclusion We have observed a heightened risk of azole-resistant aspergillosis caused by A. fumigatus harboring the TR34/L98H mutation in patients with hematologic malignancies. The emergence of azole-resistant aspergillosis raises concerns for the community, highlighting the urgent need for increased surveillance and the importance of susceptibility testing and new drugs development.
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    In Vitro Activity of Ampicillin Plus Ceftriaxone Against Non-faecalis and Non-faecium Enterococcal Isolates With/Without VanC Phenotype: Clinical Implications for Infective Endocarditis. 
    (MDPI, 2024-12-05) García González, Javier; Cañas, María Alexandra; Cuervo Requena, Guillermo; Hernández Meneses, Marta; Verdejo, Miguel Ángel; Bodro, Marta; Díez de los Ríos, Javier; Gasch, Oriol; Ribera, Alba; Falces Salvador, Carles; Perissinotti, Andrés; Vidal, Bàrbara; Quintana, Eduard; Moreno Camacho, Ma. Asunción; Piquet, Maria; Roca Subirà, Ignasi; Fernández Pittol, Mariana José; San José Villar, Sol María; García de la Mària, Cristina; Miró Meda, José M. (José María), 1956- ; Hospital Clínic Endocarditis Study Group
    1) Background: Alternative antibiotics are needed to treat infective endocarditis (IE) caused by non-faecalis/non-faecium enterococci; we aimed to assess the in vitro activity of ampicillin plus ceftriaxone (AMP + CTR) against these enterococci and to describe its clinical efficacy in IE cases. (2) Methods: Time–kill curves with standard (ISI) and high (IHI) inocula were performed to test VanC isolates [3 E. casseliflavus (ECAS) and 1 E. gallinarum (EGALL)] and non-VanC isolates [1 E. durans (EDUR), 1 E. hirae (EHIR) and 1 E. raffinosus (ERAF)]. The narrative literature review of IE cases treated with AMP + CTR was analyzed alongside three study cases. Clinical outcomes were relapse and death. (3) Results: Ampicillin plus gentamicin (AMP + GEN) showed synergistic and bactericidal activity against most isolates. AMP + CTR was synergistic at ISI for EGALL, EDUR, and EHIR and bactericidal against EHIR. At IHI, indifferent activity was observed for all isolates. In IE cases treated with AMP + CTR, it was only effective for EDUR and EHIR. Clinical information for EGALL IE is lacking. For IE caused by ECAS and ERAF, AMP + CTR seems suboptimal or ineffective, respectively. (4) AMP + CTR cannot be recommended for treating IE due to ECAS/ERAF. In contrast, this combination was effective in IE caused by EDUR/EHIR and could be recommended.
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    Combined CSF α-SYN RT-QuIC, CSF NFL and midbrain-pons planimetry in degenerative parkinsonisms: From bedside to bench, and back again.
    (Elsevier B.V., 2022-06) Compta, Yaroslau; Painous Martí, Cèlia; Soto Gimeno, Marta; Pulido Salgado, Marta; Fernández Sánchez, Manel; Cámara Lorenzo, Ana; Sánchez, V.; Bargalló Alabart, Núria; Caballol, Núria; Pont-Sunyer, Claustre; Buongiorno, Maria Teresa; Martín, Nuria; Basora Macaya, Misericordia; Tió, Montserrat; Giraldo, Darly M.; Pérez Soriano, Alexandra; Zaro, I.; Muñoz, Esteban; Martí Domènech, Ma. Josep; Valldeoriola Serra, Francesc
    Introduction Differential diagnosis between Parkinson's disease (PD) and atypical parkinsonisms (APs: multiple system atrophy[MSA], progressive supranuclear palsy[PSP], corticobasal degeneration[CBD]) remains challenging. Lately, cerebrospinal fluid (CSF) studies of neurofilament light-chain (NFL) and RT-QuIC of alpha-synuclein (α-SYN) have shown promise, but data on their combination with MRI measures is lacking. Objective (1) to assess the combined diagnostic ability of CSF RT-QuIC α-SYN, CSF NFL and midbrain/pons MRI planimetry in degenerative parkinsonisms; (2) to evaluate if biomarker-signatures relate to clinical diagnoses and whether or not unexpected findings can guide diagnostic revision. Methods We collected demographic and clinical data and set up α-SYN RT-QuIC at our lab in a cross-sectional cohort of 112 participants: 19 control subjects (CSs), 20PD, 37MSA, 23PSP, and 13CBD cases. We also determined CSF NFL by ELISA and, in 74 participants (10CSs, 9PD, 26MSA, 19PSP, 10CBD), automatized planimetric midbrain/pons areas from 3T-MRI. Results Sensitivity of α-SYN RT-QuIC for PD was 75% increasing to 81% after revisiting clinical diagnoses with aid of biomarkers. Sensitivity for MSA was 12% but decreased to 9% with diagnostic revision. Specificities were 100% against CSs, and 89% against tauopathies raising to 91% with diagnostic revision. CSF NFL was significantly higher in APs. The combination of biomarkers yielded high diagnostic accuracy (PD vs. non-PD AUC = 0.983; MSA vs. non-MSA AUC = 0.933; tauopathies vs. non-tauopathies AUC = 0.924). Biomarkers-signatures fitted in most cases with clinical classification. Conclusions The combination of CSF NFL, CSF RT-QuIC α-SYN and midbrain/pons MRI measures showed high discriminant ability across all groups. Results opposite to expected can assist diagnostic reclassification.
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    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.
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    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; Ibáñez Cuadrado, Ángela; 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; Rodríguez 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.
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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) Gonzàlez Segura, Àlex; 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; Rodríguez Ferret, Natalia ; Martínez Pinteño, Albert; Prohens Coll, Llucia; Torrent Font, Carla; García Rizo, Clemente; Mas Herrero, 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.
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    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; Rodríguez 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.
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    Prognostic risk and survival of asymptomatic IgM monoclonal gammopathy: Results from a Spanish Multicenter Registry
    (Wolters Kluwer, 2024-11-12) Moreno Fajardo, David Fernando ; 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 Rodríguez, Carlos José
    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.
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    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.
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    Current perspectives on psychedelic treatments in Europe
    (Elsevier Ltd., 2026-02-01) Madero Gómez, Santiago; Soto Angona, Oscar; Ona, Genis; Sánchez-Moreno, José; Vieta i Pascual, Eduard, 1963-
    In this viewpoint, we explore the evolving landscape of psychedelic-assisted therapy in Europe, focusing on clinical, regulatory, and therapeutic developments. While access remains limited, recent initiatives in Switzerland, Germany, and the Czech Republic illustrate growing momentum toward regulated use. We examine the debate surrounding psychedelics as pharmacological agents versus psychotherapeutic catalysts and argue for an integrative framework that considers neurobiological mechanisms, subjective experience, and contextual factors. We focus on how their effects, particularly those involving neuroplasticity and critical periods, may interact with psychotherapeutic processes. We highlight the importance of context and psychological support in shaping outcomes and discuss the challenges of implementing scalable care models. Regulatory fragmentation and methodological complexities continue to hinder progress, but publicly funded trials such as EPIsoDE and PsyPal offer promising examples of ethical and effective approaches. In our view, the future of psychedelic therapy lies not in simplifying its complexity, but in embracing it.
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    General population-based lung function trajectories over the life course: an accelerated cohort study
    (Elsevier Ltd., 2025-07-01) Torrent, Maties; Vicendese, Don; Vonk, Judith M.; Vries, Maaike de; Walters, Eugene H.; Wang, Gang; Wedzicha, Jadwiga A.; Jarvis, Deborah; Faner, Rosa; Gislason, Thorarinn; Granell, Raquel; Imboden, Medea; Íñiguez, Carmen; Jeong, Ayoung; Koch, Sarah; Koppelman, Gerard H.; Leynaert, Bénédicte; Melén, Erik; Perret, Jennifer; García Aymerich, Judith; Heras, Martí de las; Carsin, Anne Elie; Accordini, Simone; Agustí García-Navarro, Àlvar; Bui, Dinh S.; Dharmage, Shyamali C.; Dodd, James W.; Eze, Ikenna; Gehring, Ulrike; Probst-Hensch, Nicole M.; Santa Marina, Loreto
    Background Lung function is a key determinant of health, but current knowledge on lung function growth and decline over the life course is based on fragmented, potentially biased data. We aimed to empirically derive general population-based life course lung function trajectories, and to identify breakpoints and plateaus. Methods We created an accelerated cohort by pooling data from eight general population-based child and adult cohort studies from Europe and Australia. We included all participants with information on lung function, smoking status, BMI, and asthma diagnosis status from at least two visits. We used cross-classified three-level linear mixed models to derive sex-specific life course trajectories of FEV1, forced vital capacity (FVC), and FEV1/FVC ratio based on observations at ages 4–80 years, and Bayesian time-series decomposition to identify breakpoints and plateaus. We repeated sex-specific analyses with separate stratification for asthma status (never had asthma vs persistent asthma, where persistent was defined as the risk factor being present at all participant visits) and smoking status (never smoker vs persistent smoker). Findings The accelerated cohort included 30 438 participants born between 1901 and 2006 (15 703 [51·6%] female and 14 735 [48·4%] male; mean age 26 [SD 16] years), who provided a total of 87 666 observations (range 2–8 observations per participant). In female participants, FEV1 increased non-linearly in two phases, at a mean of 234 (95% CI 223 to 245) mL/year until age 13 (95% credible interval [CrI] 12 to 15) years, then at 99 (76 to 122) mL/year until a peak at age 20 (18 to 22) years, and subsequently decreased throughout the rest of adulthood (−26 [−27 to −25] mL/year). In male participants, the pattern was similar, with an increase in FEV1 of 271 (263 to 280) mL/year until age 16 (14 to 18) years, which slowed to 108 (93 to 124) mL/year until reaching a maximum at age 23 (21 to 25) years, decreasing thereafter (−38 [−39 to −37] mL/year), representing a later peak than in female participants. In female participants, FVC increased non-linearly in two phases, at 232 (95% CI 222 to 243) mL/year until age 14 (95% CrI 12 to 15) years, then at 77 (59 to 94) mL/year until peaking at age 20 (19 to 22) years, after which it decreased throughout the rest of adulthood (−26 [−27 to −25] mL/year). In male participants, FVC also increased in two phases, at 326 (315 to 337) mL/year until age 15 (13 to 17) years, then at 156 (144 to 168) mL/year until a peak at 23 (19 to 30) years, and subsequently declined in two phases (−22 [−29 to −14] mL/year until age 42 [38 to 50] years, then −36 [−38 to −34] mL/year thereafter). No plateau after the peak was observed for either lung function parameter in both sexes. FEV1/FVC ratio decreased throughout life from the starting age of 4 years in both sexes with some distinct patterns. Stratified analysis showed that persistent asthma (vs never had asthma) was related to an earlier FEV1 peak, lower FEV1 throughout adulthood, and lower FEV1/FVC ratio across the life course in both sexes. Persistent smoking (vs never smoking) was related to an accelerated decrease in FEV1 and FEV1/FVC ratio during adulthood in both sexes. No statistically significant plateau was observed in any lung function parameter across the strata of asthma or smoking status. Interpretation In both sexes, FEV1 and FVC increased in two phases, with a fast increase until around age 13–16 years, and then a slower increase until a peak. Neither parameter showed a plateau phase after the peak, and decreases started earlier than previously described. FEV1/FVC ratio decreased throughout life. These observations provide an essential, but previously unavailable, framework to assess and monitor lung health over the life course.
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    HER2DX ERBB2 mRNA score in first-line advanced HER2-positive breast cancer treated with chemotherapy, trastuzumab, and pertuzumab
    (Springer Nature, 2025-04-25) Sánchez-Bayona, Rodrigo; Martínez-Sáez, Olga; Romero-Romero, Denys; Seguí, Elia; Carcelero San Martin, Esther ; Tolosa, Pablo; Soberino, Jesús; Alva, Manuel; Pascual, Tomás; Lema, Laura; Garcia-Fructuoso, Isabel; Cobos-Fernandez, Maria Angeles; Rey, Maria; Manso, Luis; Aguirre, Ángela; Madariaga, Ainhoa; Sirenko, Valeria; González-Deza, Cristina; Blasco, Paula; Mayhua, Astrid; Castillo, Oleguer; Galván, Patricia; Sanfeliu, Esther; Villacampa, Guillermo; Buckingham, Wesley; Marín-Aguilera, Mercedes; Paré, Laia; Villagrasa, Patricia; Perou, Charles M.; Maues, Julia; Brasó-Maristany, Fara; Ciruelos, Eva; Prat Aparicio, Aleix
    In advanced HER2-positive breast cancer, the standard taxane-trastuzumab-pertuzumab (THP) regimen faces competition from new therapies, emphasizing the need for biomarkers to guide treatment. This study evaluates the HER2DX <em>ERBB2</em> mRNA score as a prognostic predictor, aiming to tailor treatment strategies. We retrospectively analyzed 94 patients treated with the THP regimen between 2010 and 2024. The HER2DX <em>ERBB2</em> mRNA score was categorized as low (<em>n</em> = 14), medium (<em>n</em> = 20), or high (<em>n</em> = 60), and its correlation with progression-free survival (PFS) and overall survival (OS) was assessed using Cox regression models. The median follow-up was 31.5 months. Patients with <em>ERBB2</em>-high scores had significantly better median PFS (33.9 vs. 10.6 months, hazard ratio [HR] = 0.40, 95% CI: 0.24–0.69, <em>p</em> < 0.001) and OS (not reached vs. 30.8 months, HR = 0.26, 95% CI: 0.13–0.49, <em>p</em> < 0.001) compared to <em>ERBB2</em>-low patients. Based on these findings, further validation of this biomarker in tumor samples from the CLEOPATRA phase III trial is ongoing, which could help optimize treatment strategies in this population.
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    Patient-reported outcomes from DESTINY-Breast04: trastuzumab deruxtecan versus physician's choice of chemotherapy in patients with HER2-low mBC
    (AlphaMed Press, 2025-05-08) Ueno, Naoto T.; Cottone, Francesco; Dunton, Kyle; Jacot, William; Yamashita, Toshinari; Sohn, Joohyuk; Tokunaga, Eriko; Prat Aparicio, Aleix; Tsurutani, Junji; Park, Yeon Hee; Rugo, Hope S.; Xu, Binghe; Cardoso, Fatima; Mitri, Zahi; Mahtani, Reshma; Orbegoso Aguilar, Cecilia; Xiao, Feng; Harbeck, Nadia; Cameron, David A.; Modi, Shanu
    Background: The phase 3 DESTINY-Breast04 trial demonstrated superior efficacy and acceptable safety with trastuzumab deruxtecan (T-DXd) vs physician's choice of chemotherapy in previously treated patients with human epidermal growth factor receptor 2 (HER2)-low metastatic breast cancer (mBC). We report the patient-reported outcomes (PROs), focusing on the hormone receptor-positive cohort. Patients and methods: Patients were randomized 2:1 to T-DXd (5.4 mg/kg intravenously every 3 weeks) or physician's choice of chemotherapy and prospectively assessed for PRO measures. Change from baseline and time to definitive deterioration (TDD) were calculated from the EORTC QLQ-C30 and QLQ-BR45 and the EQ-5D-5L questionnaires. Results: Baseline global health status/quality of life (GHS/QoL) scores were similar between groups (T-DXd, 331 patients; physician's choice, 163 patients); there were no clinically meaningful changes while on either treatment (median duration: T-DXd, 8.2 months; physician's choice, 3.5 months). Median TDD for GHS/QoL was delayed with T-DXd vs physician's choice (11.4 vs 7.5 months, respectively; hazard ratio, 0.69; 95% CI, 0.52-0.92). Median TDD for all prespecified PROs, including pain, favored T-DXd. In an additional analysis, the median TDD was shorter for nausea and vomiting with T-DXd vs the physician's choice. Conclusions: Trastuzumab deruxtecan maintained GHS/QoL scores despite a longer treatment course compared with standard chemotherapy and delayed definitive deterioration across all prespecified PROs vs the physician's choice. Appropriate management of adverse events and use of preventive measures (ie, antiemetic prophylaxis) may further support patient health-related quality of life. These findings reinforce the benefit of T-DXd as an option for patients with HER2-low mBC. ClinicalTrials.gov: NCT03734029.
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    DNA methylation patterns and epigenetic aging associated with suicide attempts in bipolar disorder
    (Elsevier B.V., 2025-08-24) Mitjans Niubó, Marina; Acosta-Díez, Miriam; Giménez Palomo, Anna; Zafrilla-López, Marina ; Saiz, Pilar A.; Barrot i Feixat, Carme; Jiménez Martínez, Esther; Papiol, Sergi; Defez Torán, Javier; Xifró Collsamata, Alexandre; Ortega Sánchez, Marisa; Ruiz, Victoria; Gavín, Patrícia; García Portilla González, María Paz, 1962-; González-Blanco, Leticia; Bobes García, Julio; Schulze, Thomas G.; Vieta i Pascual, Eduard, 1963-; Benabarre, Antonio; Arias Sampériz, Bárbara
    Background: Suicidal thoughts and behaviors (STBs) are a public health issue highly prevalent in bipolar disorder (BD). Multiple factors contribute to STBs, and new evidence highlights the significant role of epigenetics, specifically DNA methylation (DNAm). Additionally, recent studies found accelerated epigenetic aging (EA) in both BD and STBs. This study aimed to detect epigenetic risk factors for STBs, particularly for suicide attempts (SAs), comparing DNAm patterns and EA between BD patients with (BD/SA) and without (BD/non-SA) a history of SAs. Moreover, EA was calculated to explore age acceleration (AgeAccel) in the BD/SA group. Methods: Genome-wide DNAm patterns of blood samples from 46 BD/SA and 32 BD/non-SA were assessed using Infinium HumanMethylationEPIC v1.0 BeadChip (Illumina). Differentially methylated positions (DMPs) and regions (DMRs) were compared between groups. Gene network analysis was performed using genes mapped to DMPs and DMRs. Lastly, EA from different epigenetic clocks was estimated and compared between groups. Results: We identified 18 DMPs and 2 DMRs (adjusted p-value < 0.05) between BD/SA and BD/non-SA. Among the 18 genes mapped to DMPs and DMRs, the MAD1L1 gene was previously associated with severe SAs. Trends of AgeAccel using the GrimAge and GrimAge2 clocks (p-value ≤ 0.022; adjusted p-value > 0.05) were found in BD/SA. Limitations: Relatively small sample size, cross-sectional design, and use of peripheral blood. Conclusions: Our findings highlight the importance of considering epigenetic markers when studying SAs in mental disorders. These results may contribute to a better understanding of the biological basis of SAs in BD, which could ultimately help identify at-risk individuals for SAs.
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    Impact of piR_004530 reactivation in lung cancer: implications for recurrence and survival of lung squamous cell carcinoma patients.
    (BioMed Central, 2025-10-07) He, Yangyi; Acosta Plasencia, Melissa; Sánchez Lorente, David; Viñolas Segarra, Núria; Martínez Hernández, Daniel; Díaz Sánchez, Tania; Altuna Coy, Antonio; Na, Risha; Liu, Yi; Boada, Marc; Guirao Montes, Àngela; Molins López-Rodó, Laureano; Marrades Sicart, Ramon Ma.; Navarro Ponz, Alfons
    Background PIWI-interacting RNAs (piRNAs) are germline-characteristic small noncoding RNAs whose reactivation has been recently observed during carcinogenesis because of the germline reactivation program, which can be considered a hallmark of cancer. We evaluated the prognostic impact of hsa_piR_004530 reactivation in non-small cell lung cancer (NSCLC) and studied its functional role in cell lines and organoids. Methods A total of 243 NSCLC resected patients were analyzed. Hsa_piR_004530 expression was quantified in tumor (n = 243) and normal tissue (n = 31) using qRT-PCR. Tumor recurrence, disease-free survival (DFS), and overall survival (OS) were used as clinical endpoints in survival analysis. Cox regression models were generated, and decision curve analysis for assessment of clinical benefit on disease prognosis was used. The effect of hsa_piR_004530 overexpression was assessed in NSCLC cell lines by cell migration, invasion, proliferation, apoptosis, and colony formation analysis. Patient-derived organoids from SCC patients were generated, and cell viability was evaluated after piRNA overexpression. Results Hsa_piR_004530 became reactivated on the tumor compared to normal tissue and was overexpressed in SCC patients. The prognosis analysis in the whole cohort showed that patients with high levels of hsa_piR_004530 had shorter DFS and OS. However, the subanalysis by histology revealed that the true prognostic impact of hsa_piR_004530 was specifically on SCC patients. These results became validated in an additional cohort. SCC patients with high hsa_piR_004530 had a higher relapse rate and shorter DFS and OS. Hsa_piR_004530 emerged as an independent prognostic factor in the multivariate analysis. Since the SCC patients who received adjuvant treatment had the best postsurgical prognosis, we focused on the role of hsa_piR_004530 on non-treated patients, which allowed us to identify a high-risk group where the piRNA ameliorated patients’ risk stratification, highlighting superior clinical benefit in postsurgical relapse prediction. Hsa_piR_004530 overexpression was associated with increased migration, invasion, and colony formation. Moreover, the overexpression induced stem cell gene activation and correlated with higher size spheroid formation. In patient-derived organoids, the overexpression boosted organoid cell viability. Conclusions Hsa_piR_004530 became reactivated in NSCLC, where it played a role as an oncogene, and its higher levels correlated with disease recurrence and shorter survival in SCC patients.
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    Do patients with bipolar disorder and subsyndromal symptoms benefit from funcional remediation? A 12-month follow-up study
    (Elsevier B.V., 2017-04) Sánchez-Moreno, José; Bonnín Roig, Caterina del Mar; González-Pinto, Ana; Amann, Benedikt L.; Solé Cabezuelo, Brisa; Balanzá-Martínez, Vicent; Arango, Celso; Jiménez Martínez, Ester; Tabarés-Seisdedos, Rafael; García-Portilla González, María Paz, 1962-; Ibáñez Cuadrado, Ángela; Crespo, J. M. (José Manuel); Ayuso Mateos, José Luis; Vieta i Pascual, Eduard, 1963-; Martínez-Arán, Anabel, 1971-; Torrent Font, Carla; CIBERSAM Functional Remediation Group
    We analyzed the efficacy of functional remediation, in a sample of patients with bipolar disorder who presented with subsyndromal symptoms. From a total sample of 239 patients with bipolar I and II disorder, according to DSM-IV-TR diagnostic criteria, entering a randomized clinical trial, those patients who presented with subsyndromal symptoms were selected based on a method already described by Berk and colleagues was applied. It consists of using the Clinical Global Impression-Bipolar version (CGI-BP) to establish the scores of the Hamilton Depression Rating Scale (HAM-D) and of the Young Mania Rating Scale (YMRS) that correspond with 1 in the CGI-BP. Functional outcome and mood symptoms were assessed at 6 and at 12-month follow-up. A total of 99 patients were selected for this post-hoc analysis, allocated as follows: functional remediation (n=33); psychoeducation (n=37) and treatment as usual (TAU,n=29). The repeated-measures analyses at 12-month follow-up revealed a significant group x time interaction in favour of the patients who received functional remediation when compared to psychoeducation and TAU (F=2.93; p=0.02) at improving psychosocial functioning. Finally, mood symptoms did not significantly change in any of the three groups at any time of follow-up, as shown by the non-significant group x time interaction effect in HAM-D scores (F=1.57; p=0.18) and YMRS scores (F=1.51; p=0.20). Bipolar patients with subsyndromal symptoms improve their functional outcome when exposed to functional remediation regardless of the persistence of mood symptomatology.
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    The importance of organizational variables in treatment time for patients with ST-elevation acute myocardial infarction improve delays in STEMI
    (Elsevier, 2021-06-03) Berga Congost, Gemma; Brugaletta, Salvatore; Valverde Bernal, Jonatan; Marquez Lopez, Adrian; Ruiz Gabalda, Judit; Garcia Picart, Joan; Puig Campmany, Mireia; Martínez Momblan, Mª Antonia
    Background: The time between arrival at the emergency department (ED) and balloon (D2B) in STEMI is one of the best indicators of the quality of care. Our aim is to describe treatment times and evaluate the causes of delay. Methods: This is an observational retrospective study, including all consecutive STEMI code patients ≥18 years old treated in the ED from 2013 to 2016.All the patients were stratified into two groups: delayed group with D2B > 70 min and non-delayed ≤70. The primary variable was D2B time. Findings: In total 327 patients were included, stratified according to their D2B as follows: 166 (67·48%) in the delayed group and 80 (32·52%) in the non-delayed group. The delayed group was older (p = 0·005), with more females (p = 0·060) and more atypical electrocardiogram (ECG) STEMI signs or symptoms (p = 0·058) (p = 0·087). Predictors of shorter D2B time were: typical STEMI ECG signs and short training sessions for nurses on identifying STEMI patients. Interpretation: There are delays particularly in specific groups with atypical clinical presentations. Short training sessions aimed at emergency nurses correlate with shorter delay. This suggests that continuing training for emergency nurses, along with organizational strategies, can contribute to increasing the quality of care