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Heterogeneity of reduced FEV1 in early adulthood: A looking forward, looking backwards analysis
(Blackwell, 2025-01-12) Olvera Ocaña, Núria; Agustí García-Navarro, Àlvar; Vonk, Judith M.; Wang, Guangchuan; Hallberg, J.; Boezen, H.M.; Berge, Maarten van den; Melén, Erik; Faner, Rosa
Background Some individuals never achieve normal peak FEV1 in early adulthood. It is unknown if this is due to airflow limitation and/or lung restriction. Methods To investigate this, we: (1) looked forward in 19,791 participants in the Dutch Lifelines general population cohort aged 25–35 years with 5-year follow-up; and (2) looked backwards in 2032 participants in the Swedish BAMSE birth cohort with spirometry at 24 years of age but also at 16 and/or 8 years. Results (1) In Lifelines 8.5% of participants had reduced FEV1 at 25–35 years, 68% due to Preserved Ratio Impaired Spirometry (‘PRISm’) and 32% to airflow limitation (‘low-limited’); besides, 3.8% participants with normal FEV1 showed airflow-limitation (‘normal-limited’). Low-limited and normal-limited, but not PRISm, reported higher smoking exposures and asthma diagnosis than normal (p < 0.05). At 5-year follow-up, 91.2% of participants remained in the same group, and FEV1 decline was similar in normal and normal-limited participants, but statistically smaller (p < 0.05) in PRISm and low-limited; (2) these observations were largely reproduced in BAMSE at 24 years of age; and, (3) in BAMSE, low-limited or PRISm individuals were already identifiable at 8–16 years of age. Conclusion Low peak FEV1 in early adulthood is most often due to PRISm and results in a significant burden of respiratory symptoms. Only low-limited and normal-limited, but not PRISm, associate with a doctor diagnosis of asthma, and FEV1 decline was statistically different in PRISm indicating a need for differentiated clinical approaches. These spirometric abnormalities can be already identified in childhood and adolescence.
A European Survey to Identify Challenges in the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease
(John Wiley & Sons, 2025-01-03) Castera, Laurent; Alazawi, William; Bugianesi, Elisabetta; Caussy, Cyrielle; Federici, Massimo; Romero-Gómez, M.; Schattenberg, Jorn M.; Basuroy, Ron; Prasad, Preethy; Estulin, Dmitry; Lazarus, Jeffrey V.
Background and Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) and its more severe subtype, metabolic dysfunction associated steatohepatitis (MASH), are highly prevalent and strongly associated with obesity and type 2 diabetes (T2D). This study sought to identify challenges to the diagnosis, treatment and management of people living with MASLD and MASH and understand the key barriers to adopting relevant clinical guidelines. Methods: A real-world, cross-sectional study (BARRIERS-MASLD) consisting of a quantitative survey and qualitative interviews of physicians in France, Germany, Italy, Spain and the United Kingdom was conducted from March to September 2023. Descriptive statistics were used for data analysis. Results: A total of 626 physicians completed the survey; n=10 from each country participated in the qualitative interviews. Physicians considered the presence of MASH to be highly impactful on how they treated people living with obesity (66%) and T2D (69%). Over one-third (35%) of the respondents could not identify any MASH-specific clinical guidelines issued by medical societies or associations top-of-mind, but overall awareness rose when prompted about country-specific guidelines. Physicians said they would need evidence of success (48%) and clinical guidelines that address common MASLD comorbidities (38%) to increase their adoption.
In vitro and in vivo activity of daptomycin plus ceftaroline for the treatment of experimental endocarditis due to Enterococcus faecalis with and without high-level aminoglycoside resistance
(Oxford University Press, 2026-05-01) Cañas, María Alexandra; García González, Javier; Luque Paz, David; Cuervo Requena, Guillermo; Krivak, Filip; Nin Blanch, Judit; Hernández Meneses, Marta; Falces Salvador, Carles; Maristany Bosch, Marta; Perissinotti, Andrés; Vidal, Bàrbara; Tolosana, José M. (José María); Quintana, Eduard; Llopis Pérez, Jaime; Moreno Camacho, Ma. Asunción; García de la Mària, Cristina; Miró Meda, José M. (José María), 1956-; Hospital Clínic Endocarditis Study Group
Objectives Effective alternatives to standard of care treatment for E. faecalis infective endocarditis (EFIE) are needed. Some in vitro studies have suggested daptomycin and ceftaroline have synergistic activity against E. faecalis. We aimed to assess the in vitro and in vivo activity of daptomycin in combination with ceftaroline against E. faecalis clinical isolates with and without high-level of aminoglycoside resistance (HLAR). Materials and methods A panel of six endocarditis-associated E. faecalis isolates were used for time–kill assays at initial standard and high inocula. Daptomycin (10 mg/kg/day intravenously) and daptomycin (10 mg/kg/day iv) plus ceftaroline (600 mg q12 hours intravenous) were compared in vivo using a human-like pharmacokinetic model in two treatment groups using the experimental EFIE model in rabbits. Results The combination of daptomycin plus ceftaroline achieved synergy against all three HLAR and all three non-HLAR strains in time–kill assays at initial standard inoculum. A bactericidal effect was observed in two of the three HLAR E. faecalis isolates. For HLAR EFAE-188, the use of daptomycin plus ceftaroline significantly decreased the bacterial density in vegetations compared with daptomycin alone (median density 5.2 versus 6.7 log10 cfu/g; P = 0.028). For non-HLAR EFAE-468, the bacterial density in vegetations was lower with the combination therapy than with daptomycin alone (median density 5.2 versus 6.8 log10 cfu/g; P = 0.072). Adding ceftaroline prevented the development of daptomycin-resistant E. faecalis isolates in all cases. Conclusions Daptomycin plus ceftaroline represents a promising alternative for treating EFIE. Further clinical studies are needed to confirm these findings.
Increasing prevalence of self-harm, suicidal behavior and suicidal ideation throughout a three-year period in the context of COVID-19 pandemic in Spain
(Elsevier B.V., 2024-09-01) Giménez Palomo, Anna; Fico, Giovanna; Borràs, Roger; Sagué Vilavella, Maria; Gómez-Ramiro, Marta; Fortea, Adriana; Fortea González, Lydia; Vazquez, Mireia; Vieta i Pascual, Eduard, 1963-
The COVID-19 pandemic had a great impact on mental health both in the general population and in individuals with preexisting mental disorders. Lockdown, social restrictions, changes in daily habits and limited access to health services led to changes in consultations in mental health services. This study aimed to determine changing trends in psychiatric admissions by the inclusion of adult patients admitted to the Emergency Department (ED) of Hospital Clínic of Barcelona between 2019 and 2021. Acute admissions, social issues and psychiatric diagnoses were compared between years, seasons and considering the interaction between both years and seasons. A total of 13,677 individuals were included in the analysis. An overall reduction in consultations to the ED and a higher proportion of acute admissions was observed in 2020 in context of the COVID-19 outbreak. Increased prevalence of sleeping disorders and substance use disorders was found in 2020. Self-harming behavior, suicidal thoughts and suicidal behavior showed an increasing tendency over time, with their highest rates in 2021. Prevention and management strategies should be considered in order to address increasing needs in mental health car
In vitro activity of amoxicillin combined with oral cephalosporins against endocarditis-associated E. faecalis clinical isolates
(Oxford University Press, 2026-04-03) Luque Paz, David; Cañas, María Alexandra; Cuervo Requena, Guillermo; Espasa, Mateu; Hernández Meneses, Marta; Quintana, Eduard; Falces Salvador, Carles; Tolosana, José M. (José María); Vidal, Bàrbara; Perissinotti, Andrés; Llopis Pérez, Jaime; Moreno Camacho, Ma. Asunción; García de la Mària, Cristina; Miró Meda, José M. (José María), 1956-
Objectives: Aminopenicillin associated with parenteral cephalosporins provides synergistic activity against Enterococcus faecalis. Oral consolidation treatment is an option for infective endocarditis E. faecalis (EFIE), but optimal oral regimen remains under debate. We aimed to assess the in vitro activity of combinations based on amoxicillin plus an oral cephalosporin, namely, cephalexin or cefixime, against E. faecalis strains. Methods: MIC and MBC values were determined against 6 clinical isolates of endocarditis-associated E. faecalis. Time-kill (TK) experiments were performed using amoxicillin (½MIC) plus cephalexin or cefixime at different concentrations (Cmax, ½Cmax and Cmin). Comparator regimens were amoxicillin/cefazolin and amoxicillin/ceftriaxone. TK experiments were carried out at standard (∼5 × 105 cfu/mL) and high inoculum (∼108 cfu/mL). Results: Using amoxicillin combined with Cmax, ½Cmax or Cmin of oral cephalosporin at standard inoculum, synergy or additivity was observed in 66, 33 and 0% of E. faecalis isolates with adjunctive cephalexin; and in 83, 50 and 33% of isolates with adjunctive cefixime, respectively. In comparator regimens, synergy was found in all isolates at standard inoculum. At high inoculum, amoxicillin/cefixime at Cmax had similar efficacy to amoxicillin/ceftriaxone, showing synergy in 50% of E. faecalis isolates, while amoxicillin/cephalexin at Cmax and amoxicillin/cefazolin only achieved synergy in 17% of isolates. Conclusions: The combination of amoxicillin/cefixime exhibits synergy in most E. faecalis strains at standard inoculum. Cefixime could represent an interesting adjunctive therapy to amoxicillin for oral consolidation treatment of EFIE.
Impact of molecular point-of-care testing for respiratory pathogens on antibiotic use and clinical outcomes in acute respiratory tract infections: a systematic review and meta-analysis
(Elsevier, 2026-02-01) Li, Qinyuan; Zhou, Qi; Fan, Jiangbo; Feng, Xifeng; Lai, Honghao; Chen, Yaolong; Ye, Zhikang; Song, Fujian; Liu, Jiao; Chen, Dechang; Kang, Rui; Tang, Daolin; Teboul, Jean-Louis; Timsit, Jean-Francois; Torres Martí, Antoni; De Waele, Jan J.; Carratalà, Jordi; Jiang, Jianxin; Luo, Zhengxiu; Zeng, Ling
Background: Molecular point-of-care testing (mPOCT) offers rapid identification of respiratory pathogens, but its impact on antibiotic use and patient outcomes remains uncertain. We aimed to comprehensively evaluate the effects of mPOCT on antibiotic use and major clinical outcomes in patients presenting with acute respiratory tract infections (ARTIs). Methods: We searched MEDLINE, Embase, Web of Science, CENTRAL, CNKI, and Wanfang Data from inception to July 1, 2025, for randomised controlled trials (RCTs) evaluating mPOCT for patients presenting with ARTIs (PROSPERO CRD420251069333). The primary outcome was antibiotic use, assessed using pooled risk ratio (RR) with random-effects models. Risk of bias and certainty of evidence were assessed using the Risk Of Bias instrument for Use in SysTematic reviews-for Randomised Controlled Trials (ROBUST-RCT) and core Grading of Recommendations, Assessment, Development and Evaluation (GRADE), respectively. Findings: We included 25 RCTs involving 12,638 patients, of whom 61.0% were adults. Overall, mPOCT probably had little to no important effect on antibiotic use (RR 0.95, 95% CI 0.90–1.00; moderate certainty) or treatment duration (mean difference −0.44 days, 95% CI −0.98 to 0.09; moderate certainty). In adults, high-certainty evidence showed no effect on antibiotic use (RR 1.00, 95% CI 0.98–1.02), whereas in children, low-certainty evidence suggested a potential reduction (RR 0.79, 95% CI 0.65–0.97). Although mPOCT increased appropriate antibiotic prescribing (RR 2.07, 95% CI 1.55–2.77; moderate certainty), it did not affect 30-day mortality (RR 0.97, 95% CI 0.82–1.15; high certainty) and intensive care unit admission (RR 0.90, 95% CI 0.65–1.25; high certainty). Interpretation: Moderate to high certainty evidence suggests that mPOCT does not meaningfully reduce overall antibiotic use or improve patient outcomes, particularly in adults, despite enhancing prescribing appropriateness. Routine use of mPOCT for adults with ARTIs is therefore not supported. Funding: National Natural Science Foundation of China, the Postdoctoral Science Foundation, the Chongqing Municipality Joint Science and Health Major Medical Research Project, Outstanding Youth in Science and Technology, the Chongqing Youth Talent Fund, and the Research Foundation Flanders.
Palbociclib with adjuvant endocrine therapy in early breast cancer: 5-year follow-up analysis of the global multicenter, open-label, randomized phase III PALLAS trial (ABCSG-42/AFT-05/PrE0109/BIG-14-13)
(Oxford University Press, 2026-02) Mayer, Erika L.; Hlauschek, D.; Gnant, Michael F. X.; O'Brien, Peter J.; Bellet Ezquerra, Meritxell; Goetz, Matthew P.; Ruiz Borrego, Manuel; Chan, Andrew T.; Clifton, K.; Egle, D.; Lake, D.; Cabrera, P.; Mamounas, T.; Pristauz Telsnigg, G.; Dayao, Z.; Gil Gil, Miguel; Cameron, David A.; Traina, Tiffany A.; Morris, Patrick Glyn; Sabanathan, D.; Rinnerthaler, Gabriel; Meisel, Jane Lowe; Prat Aparicio, Aleix; Wolff, A. C.; Tseng, Lingming; Isaacs, Claudine; Singer, Christian F.; Rubovszky, Gábor; Foukakis, Theodoros; Jassem, Jacek; Winer, Eric P.; Vetter, Marcus; Federmann, J.; Metzger Filho, Otto
Background: In the phase III PALLAS trial, the addition of 2 years of palbociclib to adjuvant endocrine therapy (ET) did not improve short-term invasive disease-free survival (iDFS) compared with ET alone in high-risk early-stage hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer. In this article, we report 5-year efficacy outcomes, including updated iDFS and overall survival (OS). Patients and methods: PALLAS is an international, open-label, randomized phase III trial evaluating the addition of 2 years of palbociclib to adjuvant ET in patients with stage II-III HR-positive/HER2-negative breast cancer. The primary endpoint was iDFS. Results: The trial enrolled 5753 patients, with 2883 randomized to receive palbociclib plus ET and 2870 to receive ET alone. With a median follow-up of 59.8 months, the 5-year iDFS was 84.2% [95% confidence interval (CI) 82.7% to 85.6%] in the palbociclib plus ET arm and 82.4% (95% CI 80.8% to 83.9%) in the ET-alone arm [hazard ratio (HR) 0.88, 95% CI 0.77-1.01, log-rank P = 0.0614]. No significant iDFS benefit of palbociclib was observed in any subgroup, including analyses by anatomic stage, T-stage, N-stage, tumor grade, prior (neo)adjuvant chemotherapy, age, or clinical risk. The 5-year OS was 92.6% (95% CI 91.5% to 93.6%) in the palbociclib plus ET arm and 93.2% (95% CI 92.1% to 94.1%) in the ET-alone arm (HR 1.09, 95% CI 0.89-1.33, log-rank P = 0.4051). More patients in the ET-alone arm (65.7%) than in the palbociclib plus ET arm (33.0%) received cyclin-dependent kinase 4/6 inhibitors after recurrence. Conversely, more patients in the palbociclib plus ET arm (52.5%) than in the ET-alone arm (41.0%) received chemotherapy after recurrence. Conclusions: In conclusion, 5-year follow-up from the PALLAS trial confirms initially reported results. These long-term findings will provide investigators with important benchmarks for clinical outcomes in the contemporary management of HR-positive/HER2-negative breast cancer, and may be further used to guide adjuvant therapy for patients with high-risk early-stage HR-positive/HER2-negative breast cancer.
Implementation of the precision oncology program in catalonia's public health system: results, lessons learned, and future prospects
(Springer Verlag, 2026-03) Mur, Pilar; Pozuelo, Anna; Tabernero Caturla, Josep; Albanell Mestres, Joan; Bellosillo Paricio, Beatriz; Bosch Albareda, Francesc; Briones, Javier; Brunet, Joan; Colomer Pujol, Dolors; Domenech, Montserrat; Fontanet, Manel; Matias-Guiu, Xavier, 1958-; Salazar Soler, Ramón; Vivanco Hidalgo, Rosa Maria; Mollà, Meritxell; Moreno, Lucas; Prat Aparicio, Aleix; Ribera, Josep M.; Clèries Soler, Ramon; Guarga, Alex; Espinàs Piñol, Josep Alfons; Borràs Andrés, Josep Maria
Purpose: The Precision Oncology Program (POP) in Catalonia aims to provide equitable access to molecular testing for individuals with cancer, integrating Next-Generation Sequencing (NGS) into clinical practice to inform diagnosis, prognosis, and treatment decisions for both adult and pediatric patients with solid and hematologic malignancies, including somatic and germline alterations. This study evaluates the program's outcomes and impact. Methods: This evaluation covers the period from the program’s implementation in July 2021 through December 2023, with a more detailed analysis focusing on 2022–2023. The program involved 12 reference centers utilizing NGS technology for cancer genetic analysis, coordinated by CatSalut, the regional public health service payer. Data collected from each reference laboratory included the number of tests performed, types of tumor panels used, clinical indications, and associated outcomes. Results: Between July 2021 and December 2023, a total of 23,135 molecular tests were performed on 22,501 patients. The most frequently analyzed panels were for solid tumors (38.1%), hematologic cancers (17.3%), and germline mutations (42.2%). Pediatric patients accounted for 2.4% of the total. Notably, 24.7% of patients underwent a change in clinical management, contributing to more targeted treatment strategies, particularly in solid tumors (58.7%). Reports were delivered within an average of four weeks, meeting program benchmarks and facilitating timely decision-making. Sample submission compliance was high, reaching 98.5%. Conclusions: This POP successfully addressed operational, financial, and logistic challenges, ensuring equitable access to molecular testing. This program led to more efficient and personalized clinical management, with growing impact on cancer care and patient outcomes.
Contrasting the clinical and biological characteristics of young and old COPD patients
(European Respiratory Society, 2025-02-25) Vila Muntadas, Marc; Agustí García-Navarro, Àlvar; Vestbo, Jørgen; Celli, Bartolome R.; Cosío, Borja G.; Silverman, Edwin K.; Sibila Vidal, Oriol; Badia, Joan Ramon; Bakke, Per; Tal-Singer, Ruth; MacNee, William; Faner, Rosa
Background The ECLIPSE study was a large, international, prospective, controlled, observational study that included COPD patients (Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 2–4), as well as smoking and non-smoking participants with normal spirometry, aged 40–75 years, who were followed-up regularly for 3 years. Here we sought to contrast the clinical and biological characteristics of young COPD versus controls of similar age and older COPD patients included in ECLIPSE. Methods We compared 106 young (<50 years) and 488 old (>70 years) COPD patients, as well as 119 young smokers and 92 nonsmoker controls (<50 years) with normal spirometry. Results Young COPD patients: 1) were more symptomatic than young controls, often reported a family history of chronic bronchitis, emphysema and asthma, as well as a personal history of asthma and bronchitis, and suffered from a similar disease burden to older patients; 2) were at higher risk of substantial forced expiratory volume in 1 s decline over time; and 3) had reduced serum levels of CC16 (a lung-derived anti-inflammatory protein that relates to lung damage) and, at the same time, reduced pro-inflammatory markers compared to older COPD patients. Conclusions Young COPD patients suffer from significant disease burden, display an altered biomarker and disease progression profile reflected by an accelerated risk of lung function decline highlighting the need for early life diagnosis, prevention approaches and treatment.
The role of childhood maltreatment and mental health disorders on suicidal behaviour in adolescents
(Elsevier Ltd., 2025-01-01) Gómez Vallejo, Sandra; Díaz-Marsá, Marina; Fernández Rodrigues, Verónica; Andreo-Jover, Jorge; Bobes-Bascarán, T.; Cebriá, Anabel; Crespo Facorro, Benedicto; Garrido Torres, Nathalia; González-Pinto, Ana; Jiménez Treviño, Luis; Lara, Elvira; López Pena, Purificación; Palao Tarrero, Angela; Palao Vidal, Diego J.; Pérez, Víctor; Ruiz Veguilla, Miguel; Saiz Martínez, Pilar Alejandra; Sánchez Carro, Yolanda; Torre Luque, Alejandro de la; Vidal Bermejo, Emma; Vieta i Pascual, Eduard, 1963-; Zorrilla, Iñaki; Roberto, Natalia; Grande i Fullana, Iria; Bobes García, Julio; Lázaro García, Luisa; Bracco, Lorenzo; Corbalán, Fernando; Fares Otero, Natalia Elena; Ayad Ahmed, Wala; Ayuso Mateos, José Luis; Fernández Fernández, Jennifer; García Fernández, Ainoa; Garcia Ramos, Adriana; Imaz, Carlos; Leal Leturia, Itziar; Olivares, Luís; Payá, Beatriz; Pemau, Andres; Pérez Guerra, Carla; Seijo Zazo, Elisa; Tur, Nuria
Abstract Background Suicide stands as a grave and pressing public health concern, ranking among the foremost causes of death in the youth demographics. While childhood maltreatment (CM) and mental disorders have garnered substantial attention as risk factors for suicide, there remains an enigmatic aspect concerning how these two elements interact, influencing the nature of suicidal ideation and suicidal behaviour, and the transition between them. Objective This study endeavours to shed light on the intricate interplay between CM, mental disorders, and suicide. Participants and setting We gathered data from 289 adolescents aged 12–17 (87.2 % female) drawn from eight different hospitals across Spain, all of whom had attempted suicide within the past 10 days. Methods We assessed suicidal ideation severity and intensity, suicidal behaviour by attempts using the C-SSRS, and the presence of CM using CTQ and identified concurrent mental disorders according to the MINI. Regression analysis and moderation analysis were conducted by PROCESS macro. Results Moderation analysis revealed that higher scores of CM were associated with a higher number of suicide attempts with the presence of a mental disorder. Additionally, we found that those with higher scores of CM reported less severe characteristics of suicidal ideation, when presenting along with an anxiety disorder. Conclusions These findings revealed CM increased risk of suicidal behaviour among young individuals. Additionally, the results suggest that adolescents with CM and anxiety disorder might under-report suicidal ideation. Hence, these findings offer a potential key to identifying and preventing suicide risk among young individuals.
Cost during the first year after stroke by degree of functional disability: a societal perspective
(SAGE Publications, 2025-06-01) Ribó Jacobi, Marc; Abilleira, Sònia; Soler Font, Mercè; Ribera, Aida; Aznar Lou, Ignacio; Sánchez Viñas, Alba; Slof, John; Vela, Emili; Salvat Plana, Mercè; Villa García, Lorena; Serrano Blanco, Antoni; Pérez de la Osa, Natàlia
Introduction:The aim of this study was to estimate societal costs during the first year after stroke by degree of functional disability.Patients and methods:Descriptive study of the cumulative costs incurred during 1-year follow-up of a cohort of patients with stroke in Catalonia (Spain) participating in a multicentre, population-based, cluster-randomised trial (RACECAT). Patients were recruited between September 2017 and January 2019. Costs were collected for each patient from stroke onset to 1-year follow-up through hospital accounting records, electronic healthcare records and structured telephone-based interviews at 6 and 12-months follow-up. Disability was assessed using the 90-day modified Rankin Scale (mRS). Healthcare, community care, and patient/family costs were included. We used complete data from 567 eligible participants. Cost data were analysed using generalised linear models (GLMs) with gamma distributions and log link functions. For variables with >10% zero values, two-part models were applied. We performed sensitivity analyses modifying unit costs for patient/family costs.Results:Of the 567 patients included, 53% had ischaemic large vessel oclusion (LVO) stroke, 24% intracranial haemorrhage and 23% ischaemic non-LVO stroke. Mean cost per patient during the first year after stroke was €29,673 ± 28,632, and increased with degree of disability (mRS 0–2: €18,568 ± 12,244; mRS 3: €38,214 ± 28,172; mRS 4–5: €52,859 ± 36,383). Healthcare costs represented the highest proportion of total costs (63%; €18,724/patient) across all disability levels, with index hospitalisation being the highest (€12,319 ± 17,675); however, community care and patient/family costs represented over 40% of total cost in patients with higher disability levels.Discussion and conclusion:Our results are in line with other studies; the costs during the first year after stroke are high and increase with disability. These results are valuable for calculating the cost of severe stroke cases.
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.
Long-Term Observations on the European Photopatch Test Baseline Series (EPTBS) in Real Clinical Practice: 11 Years of Results in a Spanish Cohort and Suggestions for an EPTBS Update
(Wiley, 2025-04-01) Gómez Martínez, Sofia; Brufau Cochs, Magí; Iglesia Martín, Javier de la; Amat Samaranch, Victoria; Aguilera Peiró, Paula
Background The European Photopatch Testing Baseline Series (EPTBS) was published in 2013. However, limited data exist regarding the real-world clinical application of the EPTBS. Objectives This study aims to describe the photopatch test experience with the EPTBS over 11 years at a tertiary hospital in Spain. Methods A retrospective chart review spanning from February 2012 to October 2023 was conducted on patients who underwent photopatch testing (PPT) with the EPTBS. Additionally, patch testing was performed on all patients according to the European recommendations. Results Data from 148 patients were collected, and showed a PPT positivity rate of 7.4% (n = 11). Specifically, we found a photoallergic contact dermatitis (PACD) in 11/148 patients (15 positive reactions to 8 different allergens, including one patient own's product). Of them, 87% had current relevance and non-steroidal anti-inflammatory drugs (NSAIDS) were the main culprits of PACD (60%). Alternatively, we found a contact allergy to the EPTBS allergens in 14/148 (9.3%) patients, (21 positive reactions both in the irradiated and non-irradiated set to 17 different allergens, including many patients' products). Of them, UV solar filters represented the main cause of ACD. Regarding the patch testing results, we observed a positivity rate of 39.9% (116 positives in 59 different patients). The most frequent were methylchloroisothiazolinone/methylisothiazolinone, fragrance mix I and II and Myroxylon pereirae resin (balsam of Peru). Conclusion EPTBS implementation has permitted a more accurate study of PACD. Our positivity rate for PPT is slightly lower than previous reports, however the main culprits for PACD remain to be NSAIDS. The inclusion of contact allergens applied in photoexposed areas in the EPTBS could contribute to discriminating between PACD, photoaggravated ACD and ACD.
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.
A tailored approach to cardioneuroablation for reflex syncope and functional bradycardia: results from the ELEGANCE multicentre study
(Oxford University Press (OUP), 2025-12-12) Gigante, Carlo; Penela, Diego; Viveros, Daniel; Falasconi, Giulio; Teresi, Lucio; Chiara Latini, Alessia; Soto Iglesias, David ; Franco Ocaña, Paula; Francia, Pietro; Alderete, José; Turturiello, Dario; Francisco Bellido, Aldo; Zaraket, Fatima; Valeriano, Chiara; Mea, Roberta; Tonello, Bruno; Sanchez Mollá, Lautaro; De Lucia, Carmine; Matiello, María; Fernández Armenta, Juan; San Antonio, Rodolfo; Saglietto, Andrea; Ortiz Pérez, José Tomás; Martí Almor, Julio ; Berruezo, Antonio
Aims Cardioneuroablation (CNA) is a catheter-based intervention for reflex syncope and functional bradyarrhythmias that consists in the modulation of the parasympathetic cardiac autonomic nervous by targeting ganglionated plexi (GPs). To compare an ablation strategy of selective GP targeting based on clinical phenotype (tailored approach) vs. the standard approach of targeting all GPs (standard approach).Aims Cardioneuroablation (CNA) is a catheter-based intervention for reflex syncope and functional bradyarrhythmias that consists in the modulation of the parasympathetic cardiac autonomic nervous by targeting ganglionated plexi (GPs). To compare an ablation strategy of selective GP targeting based on clinical phenotype (tailored approach) vs. the standard approach of targeting all GPs (standard approach). Methods and results This is a prospective, multicentre European study (ELEGANCE study), including 123 patients who underwent CNA (73 men; median age 50 years). Among them 54 (44%) were treated with a tailored approach, targeting the superior paraseptal ganglionated plexus (SPSGP) for sinus node dysfunction and the inferior paraseptal ganglionated plexus (IPSGP) for AV block. Procedural data and clinical outcomes were compared with the remaining 69 patients treated using a standard approach. Clinical phenotypes included isolated functional sinus node dysfunction (43.1%), isolated functional AV block (9.8%), and dual presentations (47.2%). In the tailored group 1.6 +/- 0.7 GPs were targeted per patient. Compared to the standard approach, the tailored group had significantly shorter procedure times (63 vs. 85 min, P = 0.005) and reduced RF time (5.4 vs. 10.4 min, P < 0.001). Acute procedural success (tailored: 93% vs. standard: 90%, P = 0.98) and the increase in heart rate (tailored: 40 +/- 30.7% vs. standard: 40 +/- 31.4%, P = 0.96) were similar between groups. During a median 15.9 months [IQR: 9.8, 24.6] follow-up, there were no differences in syncope recurrence rate (log-rank P = 0.96). Inappropriate sinus tachycardia occurred in 8.1% of patients, (tailored 8.6% vs. standard 7.4%; P = 0.79). Conclusion An individualized CNA strategy, simplified by targeting specific GPs according to patient's pathophysiology, achieved outcomes equivalent to the standard approach while improving procedural efficiency through reduced RF delivery, shorter procedure duration, and limited ablation extent.
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).
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

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