Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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The likelihood of admission to an intensive care bed dramatically decreased in elderly patients during the first wave of the COVID-19 pandemic in Spain
(2024-08-01) Miró i Andreu, Òscar; Burillo Putze, Guillermo; Lopez-Ayala, Pedro; Aguiló, Sira; Fernández, Cesáreo; Alquézar Arbé, Aitor; González del Castillo, Juan
Background During the first wave of the COVID-19 pandemic, the availability of mechanical ventilators was very limited and ad hoc recommendations establishing age to be used for patient triage for having access to intensive care beds (ICBs) were proposed. No reports have evaluated how this policy impacted ICB admission in Western countries. Aims We analyzed the age-related probability of ICB admission during first COVID-19 pandemic wave. Materials and Methods We included all patients ≥65 years attended in 42 Spanish emergency departments (EDs) covering around 22% of the Spanish population during 1-week of the first wave of the COVID-19 pandemic (9128 ED visits) and compared the probability of ICB admission respect to patients coming to these EDs 1-week of 1-year earlier (24,128 ED visits). Results We found that compared with patients aged 65, the probability of ICB admission was significantly reduced from 79 years and up during the pandemic period (odds ratio [OR] = 0.60 for patients aged 79, 95% confidence interval [CI] = 0.39–0.94), while a significant reduction of ICB admission probabilities was found from 88 years and up during the pre-COVID-19 period (OR = 0.66 for patients aged 88, 95% CI = 0.45–0.95) (p < 0.001 for interaction). Similar results were found when analyses were limited to hospitalized or deceased patients and also after adjustment using sex and several baseline status covariates. Conclusion There was a real limitation in clinical practice of ICB admission based on age during the first wave of the COVID-19 pandemic.
Lipid droplets provide metabolic flexibility for cancer progression
(FEBS Press, 2024-05-01) Safi, Rémi; Menéndez Buján, Pablo; Pol i Sorolla, Albert
A hallmark of cancer cells is their remarkable ability to efficiently adapt to favorable and hostile environments. Due to a unique metabolic flexibility, tumor cells can grow even in the absence of extracellular nutrients or in stressful scenarios. To achieve this, cancer cells need large amounts of lipids to build membranes, synthesize lipid-derived molecules, and generate metabolic energy in the absence of other nutrients. Tumor cells potentiate strategies to obtain lipids from other cells, metabolic pathways to synthesize new lipids, and mechanisms for efficient storage, mobilization, and utilization of these lipids. Lipid droplets (LDs) are the organelles that collect and supply lipids in eukaryotes and it is increasingly recognized that the accumulation of LDs is a new hallmark of cancer cells. Furthermore, an active role of LD proteins in processes underlying tumorigenesis has been proposed. Here, by focusing on three major classes of LD-resident proteins (perilipins, lipases, and acyl-CoA synthetases), we provide an overview of the contribution of LDs to cancer progression and discuss the role of LD proteins during the proliferation, invasion, metastasis, apoptosis, and stemness of cancer cells.
Longitudinal Assessment of Abnormal Cortical Folding in Fetuses and Neonates With Isolated Non-Severe Ventriculomegaly
(John Wiley & Sons, 2025-01-01) Urru, Andrea; Benkarim, Oualid; Martí Juan, Gerard; Hahner, Nadine; Piella, Gemma; Eixarch Roca, Elisenda; González Ballester, Miguel Ángel
Purpose: The impact of ventriculomegaly (VM) on cortical development and brain functionality has been extensively explored in existing literature. VM has been associated with higher risks of attention-deficit and hyperactivity disorders, as well as cognitive, language, and behavior deficits. Some studies have also shown a relationship between VM and cortical overgrowth, along with reduced cortical folding, both in fetuses and neonates. However, there is a lack of longitudinal studies that study this relationship from fetuses to neonates. Method: We used a longitudinal dataset of 30 subjects (15 healthy controls and 15 subjects diagnosed with isolated non-severe VM (INSVM)) with structural MRI acquired in and ex utero for each subject. We focused on the impact of fetal INSVM on cortical development from a longitudinal perspective, from the fetal to the neonatal stage. Particularly, we examined the relationship between ventricular enlargement and both volumetric features and a multifaceted set of cortical folding measures, including local gyrification, sulcal depth, curvature, and cortical thickness. Findings: Our results show significant effects of isolated non-severe VM (INSVM) compared to healthy controls, with reduced cortical thickness in specific brain regions such as the occipital, parietal, and frontal lobes. Conclusion: These findings align with existing literature, confirming the presence of alterations in cortical growth and folding in subjects with isolated non-severe VM (INSVM) from the fetal to neonatal stage compared to controls.
JAK inhibitors in refractory dermatomyositis: A case series
(Wiley, 2024-11-01) Corbella Bagot, Lluís; Bosch Amate, Xavier; Gimeno Ribes, E.; Gil Lianes, Javier; Giavedoni, Priscila; Milisenda, José; Prieto González, Sergio; Hurtado García, R.; Mascaró Galy, José Manuel
This retrospective cohort study assessed the efficacy and safety of Janus kinase (JAK) inhibitors, tofacitinib and baricitinib, in 14 patients with refractory dermatomyositis (DM), a multisystemic autoimmune disorder with limited therapeutic options. Results demonstrated a significant median decrease of 21 points and a 76% reduction in the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) scores, along with a complete resolution of muscular symptoms in 64% of the patients. JAK inhibitors were effective in managing refractory DM across various subtypes with mild and manageable adverse events.
Granulocytes and mast cells in AllergoOncology—Bridging allergy to cancer: An EAACI position paper
(John Wiley & Sons, 2024-07-22) Pascal i Capdevila, Mariona; Bax, Heather J.; Bergmann, Christoph; Bianchini, Rodolfo; Castells, Mariana; Chauhan, Jitesh; Vecillas, Leticia de las; Hartmann, Karin; Izquierdo, Elena; Jappe, Uta; Jimenez Rodriguez, Teodorikez Wilfox; Knol, Edward; Levi-Schaffer, Francesca; Mayorga, Cristobalina; Poli, Aurélie; Redegeld, Frank; Santos, Alexandra F.; Jensen Jarolim, Erika; Karagiannis, Sophia N.
Derived from the myeloid lineage, granulocytes, including basophils, eosinophils, and neutrophils, along with mast cells, play important, often disparate, roles across the allergic disease spectrum. While these cells and their mediators are commonly associated with allergic inflammation, they also exhibit several functions either promoting or restricting tumor growth. In this Position Paper we discuss common granulocyte and mast cell features relating to immunomodulatory functions in allergy and in cancer. We highlight key mechanisms which may inform cancer treatment and propose pertinent areas for future research. We suggest areas where understanding the communication between granulocytes, mast cells, and the tumor microenvironment, will be crucial for identifying immune mechanisms that may be harnessed to counteract tumor development. For example, a comprehensive understanding of allergic and immune factors driving distinct neutrophil states and those mechanisms that link mast cells with immunotherapy resistance, might enable targeted manipulation of specific subpopulations, leading to precision immunotherapy in cancer. We recommend specific areas of investigation in AllergoOncology and knowledge exchange across disease contexts to uncover pertinent reciprocal functions in allergy and cancer and allow therapeutic manipulation of these powerful cell populations. These will help address the unmet needs in stratifying and managing patients with allergic diseases and cancer.
Astrocytes, via RTP801, contribute to cognitive decline by disrupting GABAergic-regulated connectivity and driving neuroinflammation in an Alzheimer's disease mouse model
(Elsevier Masson, 2025-04-01) Chicote González, Almudena; Solana Balaguer, Júlia; García Segura, Pol; Campoy Campos, Genís; Pérez Pérez, Inés; Pérez Navarro, Esther; Rodríguez Allué, Manuel José; Alberch i Vié, Jordi, 1959-; Giralt Torroella, Albert; Soria, Guadalupe; Malagelada Grau, Cristina
Introduction: Alzheimer's disease (AD) pathogenesis involves astrocytic responses to extracellular amyloid beta deposits and phospho-tau neurofibrillary tangles, which drive inflammatory activation. RTP801, a stress-responsive protein, has been implicated in mediating neuroinflammation. Its levels are increased in AD hippocampal samples, correlating with disease severity and cognitive decline. Methods: Using astrocyte-specific RTP801 silencing in the hippocampus of 5xFAD mice, we evaluated cognition, neuroinflammation, and hippocampal connectivity by magnetic resonance spectroscopy (MRS) and resting-state functional connectivity analyses. Histological and biochemical analyses assessed microgliosis, astrogliosis, and inflammasome-related protein levels. Results: Astrocytic RTP801 silencing in 5xFAD mice preserved spatial memory, maintained hippocampal γ-aminobutyric acid (GABA) levels, and preserved resting-state brain networks. In addition, RTP801 silencing significantly reduced markers of microgliosis, astrogliosis, and inflammasome effectors. Discussion: Astrocytic RTP801 contributes to AD-associated cognitive decline by disrupting GABAergic-regulated connectivity and amplifying inflammatory responses. Targeting astrocytic RTP801 may therefore offer therapeutic potential to mitigate AD progression by preserving neural connectivity and reducing neuroinflammation. Highlights: The 5xFAD mouse model of Alzheimer's disease presents higher levels of RTP801 in hippocampal astrocytes. Normalizing the levels of astrocytic RTP801 prevents cognitive decline and restores anxiety-like behavior in the 5xFAD mouse model. Knocking down astrocytic RTP801 preserves the resting-state functional connectivity in the 5xFAD mouse model. Astrocytic RTP801 mediates the loss of Parvalbumin+ interneurons, negatively affecting the levels of γ-aminobutyric acid (GABA) in the 5xFAD mouse model. Astrocytic RTP801 contributes to astro- and microgliosis and inflammasome expression in the 5xFAD mouse model.
Quantitative HER2 tissue and plasma profiling predicts the activity of trastuzumab deruxtecan for breast cancer
(Springer Nature, 2026-03-13) Tarantino, Paolo; Kim, Se-Eun; Hughes, Melissa E.; Kusmick, Ross J.; Smith, Kalie; Brasó-Maristany, Fara; Nyein Chan, Nay Nwe; Paré Brunet, Laia; Alder, Laura; Garcia Cortes, Diana; Gomez Tejeda Zanudo, Jorge; Pereslete, Alyssa M.; Noteware, Laura; Moore, Heather M.; Swearingen, Amanda E. D. Van; Li, Tianyu; Gupta, Hersh; D'Amico, Olivia; Martini, Alba; Morganti, Stefania; Spindel, Jennifer; Cook, Charmaine; McLaughlin, Christine; Dvir, Kathrin; Garrido Castro, Ana C.; Sammons, Sarah; Files, Janet L.; Sendrick, Kerry; Buck, Simone; Dillon, Deborah; Jeselsohn, Rinath; Li, Yvonne Y.; Cherniack, Andrew D.; LoRusso, Patricia; Lustberg, Maryam; Vega León, Rosario; Pardo, Francisco; Davis, Justin; Mueller, Claudius; Corgiat, Brian; Curigliano, Giuseppe; Anders, Carey K.; Petricoin, Emanuel F.; Rimm, David L.; Prat Aparicio, Aleix; Tayob, Nabihah; Lin, Nancy U.; Tolaney, Sara M.
Trastuzumab deruxtecan (T-DXd) is commonly used for treating metastatic breast cancer (MBC); however, traditional HER2 immunohistochemistry has largely failed to predict T-DXd activity. We reviewed survival outcomes and tested the reliability of multiple HER2 quantitative assays in predicting T-DXd's performance among 191 patients with MBC. We demonstrate that T-DXd's activity varies depending on the temporal evolution of HER2 immunohistochemical expression, with the longest activity observed among patients with HER2-positive disease or maintaining HER2-low disease across primary and metastatic settings. Quantitative HER2 assessment on pre-T-DXd samples showed that time-to-next treatment progressively increased by High Sensitivity-HER2 quartiles, Reverse Phase Protein Array HER2 quartiles, HER2DX ERBB2 mRNA scores and plasma-based DNADX HER2 signature tertiles (all with log-rank p < 0.05). Conversely, HER2 immunohistochemical subtypes showed limited predictive value for clinical outcomes. Additionally, elevated TOPO1 expression was associated with worse outcomes with T-DXd in HER2-negative breast cancer, suggesting potential relevance for payload-related markers in predicting T-DXd performance.
Talimogene laherparepvec and atezolizumab in HER2-negative breast cancer following neoadjuvant chemotherapy: a window-of-opportunity phase II trial (SOLTI-1503 PROMETEO)
(Nature Publishing Group, 2026-02-16) Pascual, Tomás; Vidal Losada, Maria Jesús; Cejalvo Andújar, Juan Miguel; Vega, Estela; Sanfeliu Torres, Esther ; Villacampa, Guillermo; Ganau, Sergi; Julve Parreño, Ana María; Zamora, Esther; Miranda, Ignacio; Delgado, Ana; Bermejo de las Heras, Begoña; Seguí, Elia; Brasó-Maristany, Fara; Cruz Merino, Luis de la; Juan, Manel; Galván, Patricia; González Farré, Xavier; Chillara, Samyukta; Villagrasa, Patricia; Pfefferle, Adam D.; O'Connell, Constandina E.; Ferrero Cafiero, Juan Manuel; Oliveira, Mafalda; Perou, Charles M.; Prat Aparicio, Aleix
This single-arm, phase II, preoperative window-of-opportunity trial (ClinicalTrials.gov Identifier: NCT03802604) investigated the efficacy and safety of talimogene laherparepvec (T-VEC), an oncolytic virus, with atezolizumab, an anti-PD-L1 antibody, in patients with breast cancer and radiologically and pathologically confirmed residual disease prior to surgery. Eligible patients had triple-negative breast cancer (TNBC) or hormone receptor-positive (HR+)/HER2-negative disease with a high proliferation index (Ki67 ≥ 20%) prior to neoadjuvant chemotherapy. Treatment consisted of one intratumoral injection of T-VEC (10<sup>6</sup> plaque-forming units [PFU]/mL), followed by four biweekly T-VEC doses (10<sup>8</sup> PFU/mL) plus atezolizumab (840 mg, intravenously). Among the 28 patients enrolled, 20 patients (71.4%) had HR+/HER2-negative and 8 patients (28.6%) had TNBC. At surgery, 7 patients (26.9%) achieved Residual Cancer Burden (RCB)-0/I (primary endpoint), 12 (46.2%) RCB-II and 7 (26.9%) RCB-III. Safety profile was favorable, with mostly low-grade adverse events and no serious events (secondary endpoint). Therapy induced immune modulation, including increased tumor-infiltrating lymphocytes, elevated PD-L1 expression, and enhanced immune-related gene signatures (exploratory endpoints). The trial met its pre-specified efficacy and safety endpoints. These findings support the feasibility of T-VEC plus atezolizumab as a preoperative immunotherapy approach for managing HER2-negative residual disease post-neoadjuvant chemotherapy and warrant further exploration in larger trials.
Impact of cognitive reserve in clinical, neurocognitive and lifestyle factors in chronic schizophrenia and early stages of schizophrenia
(Elsevier España, 2024-07-01) Amoretti Guadall, Silvia; Arranz, Belén; Anmella, Gerard; Bernardo Arroyo, Miquel; Alfonso, Miqueu; Hernández, Carla; García-Portilla González, María Paz, 1962-; González-Blanco, Leticia; Safont, Gemma; Garrido, Ignacio; Sanchez Autet, Mónica
Introduction Although there is evidence that higher cognitive reserve (CR) is a protective factor and it has been related to better prognosis, there have been no studies to date that have explored the CR level and its impact in clinical, neurocognitive and lifestyle outcomes according to the stage of the disease: early stage of psychosis (ESP) or chronic schizophrenia (SCZ). Material and methods A total of 60 patients in the ESP and 225 patients with SCZ were enrolled in the study. To test the predictive capacity of CR for each diagnostic group, a logistic regression analysis was conducted. Hierarchical linear regression analyses were performed to explore the associations between CR and different outcomes. The mediation analyses were performed according to the principles of Baron and Kenny. Results Patients with SCZ showed lower CR than those in the ESP (p < 0.001). CR correctly classified 79.6% of the cases (p < 0.001; Exp(B) = 1.062). In ESP group, CR was related to working memory (p = 0.030) and negative symptoms (p = 0.027). CR (t = 3.925, p < 0.001) and cannabis use (t = 2.023, p = 0.048) explained 26.7% of the variance on functioning (p = 0.003). In patients with SCZ, CR predicted all cognitive domains, negative symptoms (R2 = 0.091, p = 0.001) and functioning (R2 = 0.074, p = 0.005). In both ESP and SCZ groups, higher CR was associated with lower body mass index and circumference. In ESP group, the effect of adherence to Mediterranean diet on functioning (p = 0.037) was mediated by CR level (p = 0.003).
Dynamic biomarkers in hormone receptor-positive/HER2-negative breast cancer trials: a new hope for precision oncology
(Springer Nature, 2026-01-28) Grazia, Giuseppe Di; Schettini, Francesco; Sánchez Bayona, Rodrigo; Casals Pascual, Climent; Pascual, Tomás; Generali, Daniele; Gennari, Alessandra; Vigneri, Paolo; Harbeck, Nadia; Cortés, Javier; Prat Aparicio, Aleix
Hormone receptor-positive/HER2-negative breast cancer evolves in response to therapy, demanding smarter, adaptive biomarker-based treatment strategies. We review emerging dynamic biomarkers to guide therapeutic decision-making, spanning tissue and liquid biopsies, metabolic imaging, and microbiome profiling, that capture tumor or host-related changes over time. By contrasting Academic and Industry approaches, we advocate for a cultural shift in clinical trial design and implementation, aiming to move from reactive to proactive Oncology.
Neoadjuvant palbociclib and endocrine therapy versus chemotherapy in ER + /HER2- breast cancer: a randomized phase II trial
(Nature Publishing Group, 2026-04-08) Pascual, Tomás; Gavilá, Joaquín; Prat Aparicio, Aleix; Perou, Charles M.; Brandberg, Yvonne; Bergh, Jonas; Hatschek, Thomas; Foukakis, Theodoros; Johansson, Hemming; Hellström, Mats; Agartz, Susanne; Grybäck, Per; Salgkamis, Dimitrios; Zerdes, Ioannis; Wang, Kang; Hartman, Johan; Acs, Balazs; Sun, Wenwen; Matikas, Alexios; Tzoras, Evangelos; Sarafidis, Michail; Sifakis, Emmanouil G.; Bjöhle, Judith; Barnekow, Elin; Margolin, Sara; Isaksson Friman, Erika; Edman Kessler, Luisa; Zouzos, Athanasios; Boyaci, Ceren; Villacampa, Guillermo
n PREDIX LumB patients with estrogen receptor positive and human epidermal growth factor receptor negative (ER + /HER2-) breast cancer > 20 mm and/or with lymph node metastasis were randomized 1:1 to receive either paclitaxel weekly for 12 weeks followed by palbociclib and endocrine therapy for 12 weeks (arm A), or the reverse sequence (arm B). Primary endpoint is objective radiologic response at 12 weeks (ORR12), and key secondary endpoints are ORR24, pathologic complete response, event-free survival, safety and correlative studies of tissue and circulating biomarkers. Whole exome sequencing and RNA sequencing were performed on baseline fresh frozen tissue samples. In total, 179 patients comprise the intention-to-treat population. There is no statistically significant difference between the two arms in ORR12 (59% vs 45%, p = 0.058). An exploratory gene expression analysis identified differentially expressed genes and gene sets between responders and non-responders at 12 weeks. A predictive signature, CDKPredX, comprising 31 genes related to proliferation, ER signaling and immune activity was developed to identify patients resistant to chemotherapy but responding to palbociclib plus endocrine therapy (pinteraction=0.03). The predictive signature was independently validated in the CORALLEEN trial (pinteraction=0.048). Clinicaltrials.gov identifier: NCT02603679
Real-world second- and third-line progression-free survival after progression on first-line CDK4/6 inhibitors in HR+/HER2- metastatic breast cancer by PAM50 intrinsic subtype: the SOLTI-1801 CDK-PREDICT study
(Springer Verlag, 2026-02-28) Tolosa, Pablo; Garcia Fructuoso, Isabel; Pascual, Tomás; Martínez-Sáez, Olga; Cejalvo Andújar, Juan Miguel; Servitja, Sonia; Fernández Abad, María; Benitez Fuentes, Javier David; Brasó-Maristany, Fara; Sanfeliu Torres, Esther ; Lema, Laura; Ruano, Yolanda; Parrilla, Lucía; Roncero, Ana María; Cobos-Fernandez, Maria Angeles; Díaz, Irene; Centelles López, Karla Alicia; Sánchez Bayona, Rodrigo; Alva, Manuel; Madariaga, Ainhoa; Villacampa, Guillermo; Salvador, Fernando; Sánchez Belmonte, Agustín; Malumbres, Marcos; Prat Aparicio, Aleix; Ciruelos, Eva
Purpose: Estrogen receptor-positive (ER+), HER2-negative (HER2-) metastatic breast cancer (MBC) shows variable outcomes after first-line CDK4/6 inhibitors (CDK4/6i) plus endocrine therapy (ET). The prognostic role of PAM50 intrinsic subtypes (IS) in this setting remains unestablished. We evaluated IS and biomarker profiles in the SOLTI-1801 CDK-PREDICT cohort, focusing on real-world second- and third-line progression-free survival (rwPFS-2L and rwPFS-3L). Methods: This multicenter observational study reports a post hoc secondary analysis of ER+ /HER2- MBC patients previously treated with first-line CDK4/6i plus ET. Baseline metastatic biopsies were molecularly profiled (PAM50, CCNE1, PDCD1) using the nCounter platform. rwPFS-2L and rwPFS-3L were defined from initiation of second- or third-line therapy to progression or death. Kaplan-Meier and Cox models assessed associations with clinical, molecular, and treatment variables. Results: Among evaluable patients (n = 125 for rwPFS-2L; n = 95 for rwPFS-3L), Luminal A/B subtypes represented most cases, while advanced lines showed more aggressive profiles. Median rwPFS-2L was 7.2 months in luminal IS vs. 6.1 in non-luminal (HR 1.40; 95% CI 0.86-2.30); the Basal-like (BL) subtype correlated with significantly shorter rwPFS-2L (HR 3.82; 95% CI 1.07-13.63). In rwPFS-3L, similar trends were seen (6.4 vs. 3.3 months; HR 1.74; 95% CI 0.98-3.08), with BL showing the poorest outcomes (HR 5.63; 95% CI 1.17-27.02). High CCNE1 expression was linked to shorter rwPFS-2L (HR 1.22; 95% CI 1.02-1.47). Targeted agents were frequent in 2L (51%) and capecitabine in 3L (36%), while endocrine monotherapy yielded poorest rwPFS. Conclusions: Outcomes after CDK4/6i progression differ by PAM50 IS, supporting its role in guiding post-progression treatment.
Validation of the HER2DX genomic test in first-line advanced HER2-positive breast cancer treated with trastuzumab, pertuzumab, and taxane
(Springer Nature, 2026-02-10) Kubeczko, Marcin; Cobo, Sandra; Sánchez Bayona, Rodrigo; Pycinski, Bartlomiej; Soberino, Jesús; Chmielik, Ewa; Sanfeliu Torres, Esther ; Rey, Maria; Pardo, Francisco; Aguirre, Ángela; Castillo, Oleguer; Lesniak, Aleksandra; Oczko-Wojciechowska, Malgorzata; Carcelero San Martin, Esther; Adamo, Barbara; Vidal Losada, Maria Jesús; Bergamino Sirvén, Milana; Maues, Julia; Villacampa, Guillermo; Paré, Laia; Villagrasa, Patricia; Ciruelos, Eva; Prat Aparicio, Aleix; Jarzab, Michal; Brasó-Maristany, Fara
Trastuzumab, pertuzumab, and a taxane (THP) has been the standard first-line therapy for HER2+ advanced breast cancer for over a decade. With new regimens emerging, genomic tools like HER2DX may help identify patients who benefit durably from THP versus those requiring intensification. Here, baseline tumor tissue from 122 patients with HER2+ treated with THP in Poland was tested with HER2DX. A previously published Spanish real-world cohort (n = 93) was added to generate a combined cohort (n = 215). Univariable analyses were performed in the Polish cohort, and multivariable Cox and logistic regression models were applied to the combined cohort. A HER2DX metastatic prognostic score was trained on overall survival (OS) in the Spanish cohort and validated in the Polish cohort. In the Polish cohort, high ERBB2 mRNA scores were associated with significantly longer real-world progression-free survival (rwPFS) (33.8 vs. 17.9 months; hazard ratio [HR] 0.57; p = 0.022) and real-world overall survival (rwOS) (75.1 vs. 40.2; HR 0.48; p = 0.009). In the combined cohort, ERBB2 high-score tumors showed prolonged rwPFS (33.8 vs. 12.5; HR 0.50; p < 0.001) and rwOS (not reached vs. 37.1; HR 0.36; p < 0.001), and higher rwORR (84.4% vs. 52.0%; p < 0.001). Prognostic value was independent of clinical variables, including number of metastatic sites. Subgroup analyses showed particularly favorable outcomes in patients with <3 sites (median rwPFS 51.7 vs. 20.3 months). The HER2DX metastatic prognostic score outperformed ERBB2 alone in the validation cohort. In conclusion, the HER2DX ERBB2 mRNA score provides independent prognostic information in HER2+ advanced breast cancer treated with THP. The HER2DX metastatic prognostic score further improves prognostic accuracy.
Hidradenitis suppurativa in patients with inflammatory bowel disease: a national multicenter study from the GETECCU-ENEIDA Registry
(SAGE Publications, 2026-02-18) Madero-velázquez, Lucía; De Francisco, Ruth; Herreros, Belen; Yagüe, Carmen; Bujanda, Luis; Calvet, Xavier; Ponferrada, Angel; Aguas, Mariam; Rodríguez-moranta, Francisco; Marín-jiménez, Ignacio; Catalá, Lourdes; Gargallo-pueyo, Carla; Huguet, José; Mesonero, Francisco; Monfort, David; Sierra-ausín, Mónica; Igualada, Laura; Ricart-gomez, Elena; González-vivo, María; José García, María; Hernandez Camba, Alejandro; Elorza, Ainara; Zabalza-san Martín, Lucía; Ramos, Laura; Martín-arranz, María Dolores; Ruiz-núñez, Isabel; Martínez-montiel, Pilar; Soto, Pilar; Roig, Cristina; Molina, María; Mañosa, Miriam; Alba, Cristina; Barreiro-de Acosta, Manuel; P. Gisbert, Javier; Ramírez De La Piscina, Patricia; Lorente, Rufo; Zabana, Yamile; Botella, Belen; Riestra, Sabino; Belen-galipienso, Olivia; Busquets, David; Argüelles, Federico; Pascual, José Carlos; Zapater, Pedro; Domènech, Eugeni; Gutiérrez, Ana
Background: Hidradenitis suppurativa (HS) is a chronic, recurrent skin disease that may be associated with inflammatory bowel disease (IBD). Objectives: This study aimed to describe the features and therapeutic requirements of IBD and HS in patients who present both entities and the risk factors for HS development in patients with IBD. Methods: Case-controlled, retrospective study of all patients diagnosed with IBD-HS in the ENEIDA registry. Cases were paired 1:2 with controls (IBD without HS). Design: This was a retrospective, case-control study. Results: A total of 819 patients were included: 273 patients with IBD-HS and 546 controls. Female sex (62% vs 44%, p = 0.0001), active smoking (45% vs 18%, p = 0.0001), Crohn's disease (CD; 83% vs 55%, p = 0.0001), perianal disease (59% vs 33%, p = 0.0001), extraintestinal manifestations (38% vs 17%, p = 0.0001), and psychiatric disorders (18% vs 2%, p < 0.05) were more frequent among patients with IBD-HS than in controls. The average body mass index was greater in the IBD-HS group. The most frequently HS-affected locations were axillary (57%) and genital (43%) areas. Use of biologicals and CD-related perianal surgery was more common among patients with CD-HS (77% vs 66%, p = 0.003; 37% vs 13%, p < 0.001), compared to controls with only CD. Conclusion: Patients with IBD-HS exhibit a distinctive phenotype with higher therapeutic requirements for the subset of patients with CD-HS compared to those without HS. Assessment of this comorbidity should be considered in patients with suggestive skin lesions and IBD to improve the outcomes of both conditions.
Biological therapies for inflammatory pouch disorders: insights and outcomes from the RESERVO study of GETECCU
(SAGE Publications, 2026-02-18) Mesonero, Francisco; Zabana, Yamile; Fernández-clotet, Agnès; Leo-carnerero, Eduardo; Caballol, Berta; Núñez, Andrea; José García, María; Bertoletti, Federico; Bastida, Guillermo; Suris, Gerard; Casis, Begoña; Ferreiro-iglesias, Rocío; Calafat, Margalida; Jiménez, Itxaso; Miranda-bautista, José; Javier Lamuela, Luis; Fajardo, Ingrid; Torrealba, Leyanira; Nájera, Rodrigo; Sáiz-chumillas, Rosa María; González-partida, Irene; Vicuña, Miren; García-morales, Natalia; Gutiérrez, Ana; López-garcía, Alicia; Benítez, José Manuel; Rubín De Célix, Cristina; Tejido, Coral; Brunet-mas, Eduard; Hernandez-camba, Alejandro; Suarez Ferrer, Cristina; Rodríguez-lago, Iago; Piqueras, Marta; Castaño, Andrés; Ramos, Laura; Sobrino, Ana; Rodríguez-grau, María Carmen; Elosua, Alfonso; Montoro-huguet, Miguel A.; Baltar, Ruth; Huguet, José María; Hermida, Benito; Caballero-mateos, Antonio; Sánchez-guillén, Luis; Bouhmidi, Abdel; Pajares, Ramón; Baston-rey, Iria; López-sanromán, Antonio; Albillos, Agustín; Barreiro-de Acosta, Manuel
Background: Inflammatory pouch disorders can be refractory to conventional therapy. Evidence on biological therapy from large cohorts is scarce. Objective: To explore the use and effectiveness of biological therapy for inflammatory pouch disorders. Design: A retrospective and multicentre study. Methods: We included patients diagnosed with pouchitis, Crohn's Disease of the Pouch (CDP) or cuffitis and treated with biological therapy. Effectiveness was evaluated at 12 months based on normalisation of stool frequency, absence of pain, faecal urgency or fistula discharge (clinical remission), or as any improvement in these symptoms (clinical response). We also compared the effectiveness of a second biologic after anti-tumour necrosis factor (anti-TNF) failure using descriptive and comparative statistics. Results: In total, 145 patients were included; 62% were men and the median age was 54 (20-71) years. Overall, 212 lines of treatment were evaluated (95 infliximab, 69 adalimumab, 7 golimumab, 35 vedolizumab and 26 ustekinumab). At least a second line of treatment was received by 41% of patients. Overall, 66% had chronic pouchitis and 29% had CDP. Clinical remission rates at 12 months were 45%, 44%, 43%, 39% and 45% for infliximab, adalimumab, golimumab, vedolizumab and ustekinumab, respectively. No differences were found based on the type of disease. Vedolizumab was the only treatment to show better results as a first-line therapy (50% vs 33%, p < 0.05). Thirty-nine patients received a second therapy after anti-TNF failure. Second anti-TNF use had higher risks of failure (odds ratio (OR) 4.8, 95% confidence interval (CI) 2.3-19) and discontinuation (OR 5.52, 95% CI 1.94-25.5). Conclusion: Biological therapy is a cornerstone in the treatment of pouch disorders, demonstrating consistently high effectiveness. After anti-TNF failure, another mechanism of action should be employed.
Case Report: Personalized management of HER2-positive breast cancer with advanced nodal disease during pregnancy: a clinical case and review
(Frontiers Media, 2026-01-19) Gullotta, Gullotta; Walbaum, Benjamin; Seguí, Elia; López Rojano, Marta; Mension Coll, Eduard; Cebrecos, Isaac; Mollà, Meritxell; Oses, Gabriela; Bargallo, Xavier; Ganau, Sergi; Sanfeliu Torres, Esther ; Brasó-Maristany, Fara; Muñoz Mateu, Montserrat; Prat Aparicio, Aleix; Vidal Losada, Maria Jesús; Adamo, Barbara
Background: Pregnancy-associated breast cancer (PrBC) poses complex challenges in diagnosis and treatment, particularly when associated with biologically aggressive subtypes and extensive nodal involvement. Management must be individualized, integrating oncologic urgency, fetal safety, and limited validated evidence in this unique setting.Case Summary: We present the case of a 36-year-old woman diagnosed during the second trimester of pregnancy with HER2-positive (HER2+), node-positive (cT2[m]N3a) breast cancer (BC). After a multidisciplinary team discussion, patient initiated anthracycline- and taxane-based neoadjuvant chemotherapy during gestation. Given its contraindication during pregnancy, anti-HER2 therapy was added postpartum, and surgery included nipple-sparing mastectomy with targeted axillary dissection (TAD) of clipped nodes. Pathology revealed minimal residual invasive disease in the breast and a complete axillary response, allowing omission of axillary lymph node dissection (ALND). Genomic profiling with HER2DX supported high-risk disease and informed systemic therapy with delayed anti HER2 therapy, and conservative axillary management (TAD without ALND) in cT2N3 PrBC, without compromising fetal outcome. The patient subsequently received adjuvant chest wall and nodal region radiotherapy plus trastuzumab-emtansine (T-DM1).Conclusion: This case underscores the value of personalized, multidisciplinary management in PrBC, particularly in patients with high-risk biologic features and advanced nodal disease. Integrating clinical judgment, genomic tools, and adaptive strategies, while accounting for gestational limitations, can optimize oncologic outcomes without compromising fetal safety
Spontaneous and perturbation-based EEG cortical excitability markers are associated with plasma p-tau181 concentration in healthy middle-aged adults
(Elsevier, 2024-12-30) Perellón Alfonso, Ruben; Abellaneda Pérez, Kilian; Pileckyte, Indre; Cabello Toscano, María del Rocío; Mulet Pons, Lídia; Vaqué Alcázar, Lídia; Cattaneo, Gabrielle; Redondo-Camós, María; España Irla, Goretti; Delgado Gallén, Selma; Solana Sánchez, Javier; Zetterberg, Henrik; Tormos, José María; Franzmeier, Nicolai; Pascual Leone, Álvaro, 1961-; Bartrés Faz, David
In early-stage Alzheimer's disease (AD) amyloid-β (Aβ) deposition can induce neuronal hyperactivity, thereby potentially triggering activity-dependent neuronal secretion of phosphorylated tau (p-tau), ensuing tau aggregation and spread. Therefore, cortical excitability is a candidate biomarker for early AD detection. Moreover, lowering neuronal excitability could potentially complement strategies to reduce Aβ and tau buildup. There is, however, a lack of understanding of the relationship between cortical excitability and p-tau increase in vivo. Therefore, in a sample of 658 healthy middle-aged (between the ages of 40 and 65) participants of the Barcelona Brain Health Initiative cohort study, we examined the relation of blood-based tau, phosphorylated at amino acid 181 (p-tau181), reflecting neuronal p-tau secretion; neurofilament light chain (NfL), as a passively released control for p-tau181; and electroencephalography (EEG) markers of cortical excitability. A subsample of 47 participants also completed a controlled brain perturbation approach via transcranial magnetic stimulation (TMS) with concurrent EEG. Results show that both spontaneous (i.e., resting-state) and perturbation-based TMS-EEG markers, are associated with blood p-tau181, particularly in older individuals. The perturbation-based marker was a significantly more sensitive predictor of p-tau181 concentration than the spontaneous resting state EEG-based marker. The relationships observed are not present for the NfL control. These results show that relationships between p-tau181 and cortical excitability are present in healthy middle-aged subjects and that p-tau181 increases may reflect activity-dependent secretion.
High-resolution kinetics and cellular determinants of SARS-CoV-2 antibody response over two years after COVID-19 vaccination
(Elsevier Masson SAS, 2025-02-01) Rubio Bodí, Rocío; Macià Bros, Dídac; Barrios, Diana; Vidal, Marta; Jiménez, Alfons; Molinos Albert, Luis M.; Díaz Garrido, Natalia; Canyelles, Mar; Lara Escandell, Maria; Planchais, Cyril; Santamaria, Pere; Carolis, Carlo; Izquierdo, Luis; Aguilar, Ruth; Moncunill, Gemma; Dobaño, Carlota, 1969-
Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) studies usually rely on cross-sectional data of large cohorts but limited repeated samples, overlooking significant inter-individual antibody kinetic differences. By combining Luminex, activation-induced marker (AIM) and IFN-γ/IL-2 Fluorospot assays, we characterized the IgM, IgA, and IgG antibody kinetics using 610 samples from 31 healthy adults over two years after COVID-19 vaccination, and the T-cell responses six months post-booster. Antibody trajectories varied among isotypes: IgG decayed slowly, IgA exhibited an initial sharp decline, which gradually slowed down and stabilized above the seropositivity threshold. Contrarily, IgM rapidly dropped to undetectable levels after primary vaccination. Importantly, three vaccine doses induced higher and more durable anti-spike IgG and IgA levels compared to two doses, whereas infection led to the highest antibody peak and slowest antibody decay rate compared to vaccination. Comparing with ancestral virus, antibody levels recognizing Omicron subvariants had a faster antibody decay. Finally, polyfunctional T cells were positively associated with subsequent IgA responses. These results revealed distinctive antibody patterns by isotype and highlight the benefits of booster doses in enhancing and sustaining antibody responses.
Not all severe malaria cases are severe: Is it time to redefine severity criteria for malaria in non-endemic regions?
(Elsevier, 2024-07-01) Balerdi Sarasola, Leire; Muñoz Gutiérrez, José; Fleitas, Pedro E.; Rodriguez Valero, Natalia; Almuedo Riera, Alex; Antequera, Alba; Subirà, Carme; Grafia, Ignacio; Ortiz Fernández, Maria; Alba, Tessa de; Álvarez Martínez, Míriam; Valls Lolla, Ma. Eugenia; Parolo, Claudio; Castro Rebollo, Pedro; Camprubí Ferrer, Daniel
Background: The current definition of severe malaria in non-endemic areas follows WHO criteria, which mainly target children in malaria-endemic areas, potentially misclassifying cases in non-endemic regions. We assessed the performance of a modified severe malaria classification criteria within our patient cohort. Methods: A cohort study of patients managed for malaria in a non-endemic setting (2005-2023) was analyzed. We classified patients into severe malaria (SM) using WHO 2013 criteria except for hyperparasitemia, where 2 % threshold was applied. Patients with SM were distinguished as very severe malaria (VSM) when presenting at least one of the following conditions: parasitemia >10 %, pulmonary edema, impaired consciousness, seizures, renal failure, metabolic acidosis or hyperlactatemia, shock or hypoglycemia. In patients with SM and no criteria for VSM, less severe malaria (LSM) was defined by: 2-10 % parasitemia, hyperbilirubinemia, prostration, anemia or minor bleeding. The primary composite outcome was death or the need for a life-saving intervention, as analyzed in the three comparative groups. Secondary outcome was the prevalence of co-infections. Results: Among 506 patients with malaria, 176 (34.8 %) presented with SM. A total of 37 (7.3 %) patients developed a life-threatening condition, namely death (n = 4) and/or the need for life-saving interventions (n = 34). All fatalities and 33 out of the 34 life-saving interventions occurred in the VSM group. Patients in LSM group did not develop any life-threatening conditions. As to co-infections, 28 (5.5 %) patients had a community-acquired co-infection, with no differences between groups (p = 0.763). Conclusions: Severity criteria definitions would benefit from a review when assessing patients with malaria in non-endemic areas. Within the spectrum of SM, patients reclassified as LSM have a low risk of developing a life-threatening condition and present low co-infection incidence and could benefit from management out of intensive care units and a restrictive use of empirical antibiotics.
Trends in authorship in Medicina Clínica: an 11-year analysis of author gender Tendencias en la autoría en Medicina Clínica: un análisis de 11 años sobre el género de los autores
(Elsevier España, 2024-10-25) Artiga Solana, Xenia; Muñoz Mahamud, Ernesto; Combalía Aleu, Andrés
La publicación de artículos en revistas biomédicas, fruto de la investigación de sus autores, representa una aportación científica a la comunidad, un avance en el conocimiento y en la medicina de la evidencia, pero también se relaciona con la promoción académica de los mismos1. Las perspectivas profesionales en los hospitales y en la universidad, están fuertemente vinculadas a la autoría científica. En la actualidad, las publicaciones en revistas biomédicas indexadas representan el parámetro medible de mayor importancia en los baremos para acceder a una posición estable de los autores en los centros a los que están adscritos

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