e-Repositori UPF :: Articles (Departament de Medicina i Ciències de la Vida)

Recent Submissions

The projected economic burden and complications of revision hip and knee arthroplasties: insights from national registry studies
(Wiley, 2025) Sadoghi, Patrick; Koutp, Amir; Pérez-Prieto, Daniel; Clauss, Martin; Kayaalp, M. Enes; Hirschmann, Michael
The rising volume of primary hip and knee arthroplasties has led to a parallel increase in revision surgeries, creating significant clinical and economic challenges for healthcare systems worldwide. This study synthesizes national arthroplasty registry data to evaluate trends in revision aetiology, associated costs and regional disparities. While advancements in prosthetic design have reduced aseptic loosening rates (declining to 35.1% for hips and 18.3% for knees), septic complications now account for a growing proportion of revision cases, rising to 18.2% for hips and 21.6% for knees. Additionally, instability and malalignment persist at 15.9% and 14.1%, respectively. Revision procedures are 76% more costly than primary surgeries, with two-stage septic revisions incurring costs of up to $37,297 per case. Beyond direct surgical costs, prolonged recovery and productivity loss contribute to a broader economic impact. Regional variations, such as higher periprosthetic fracture rates in England and Wales, highlight inconsistencies in data reporting and healthcare practices. Addressing these challenges requires standardized infection definitions, enhanced registry collaboration and investment in infection prevention strategies. The role of referral centres in improving outcomes and reducing costs through multidisciplinary care is increasingly recognized. By integrating evidence-based infection management protocols and leveraging emerging technologies, the orthopaedic community can optimize patient outcomes and reduce the financial burden of revising arthroplasties.
Mutations in the small nuclear RNA gene RNU2-2 cause a severe neurodevelopmental disorder with prominent epilepsy
(Nature Research, 2025) Greene, Daniel; Sevilla-Porras, Marta; Pérez Jurado, Luis Alberto; Turro, Ernest
The major spliceosome includes five small nuclear RNA (snRNAs), U1, U2, U4, U5 and U6, each of which is encoded by multiple genes. We recently showed that mutations in RNU4-2, the gene that encodes the U4-2 snRNA, cause one of the most prevalent monogenic neurodevelopmental disorders. Here, we report that recurrent germline mutations in RNU2-2 (previously known as pseudogene RNU2-2P), a 191-bp gene that encodes the U2-2 snRNA, are responsible for a related disorder. By genetic association, we identified recurrent de novo single-nucleotide mutations at nucleotide positions 4 and 35 of RNU2-2 in nine cases. We replicated this finding in 16 additional cases, bringing the total to 25. We estimate that RNU2-2 syndrome has a prevalence of ~20% that of RNU4-2 syndrome. The disorder is characterized by intellectual disability, autistic behavior, microcephaly, hypotonia, epilepsy and hyperventilation. All cases display a severe and complex seizure phenotype. We found that U2-2 and canonical U2-1 were similarly expressed in blood. Despite mutant U2-2 being expressed in patient blood samples, we found no evidence of missplicing. Our findings cement the role of major spliceosomal snRNAs in the etiologies of neurodevelopmental disorders.
Efficacy and safety of topical delgocitinib cream versus oral alitretinoin capsules in adults with severe chronic hand eczema (DELTA FORCE): a 24-week, randomised, head-to-head, phase 3 trial
(Elsevier, 2025) Giménez Arnau, Anna Maria; Pinter, Andreas; Sondermann, Wiebke; Reguiai, Ziad; Woolf, Richard; Lynde, Charles; Legat, Franz J.; Costanzo, Antonio; Silvestre Salvador, Juan Francisco; Mellerup, Natja; Østerdal, Marie Louise; Plohberger, Ursula; Ryttig, Lasse; Bauer, Andrea
Background: Chronic hand eczema is a heterogeneous, fluctuating, and long-lasting disease affecting the hands and wrists that substantially affects quality of life. For severe chronic hand eczema, topical corticosteroids are often unsatisfactory and systemic treatment can be required. The aim of the head-to-head, phase 3 DELTA FORCE trial was to evaluate the efficacy and safety of topical delgocitinib cream versus oral alitretinoin, the only currently approved systemic drug for severe chronic hand eczema. Methods: This randomised, assessor-masked, trial was conducted at 102 trial centres in Austria, Canada, France, Germany, Italy, Norway, Poland, Slovakia, Spain, and the UK. Adults (aged ≥18 years) with severe chronic hand eczema were randomly assigned (1:1) via an interactive response technology system to delgocitinib cream 20 mg/g (twice daily) or alitretinoin 30 mg (once daily) for up to 24 weeks. The primary endpoint was change in Hand Eczema Severity Index (HECSI) score from baseline to week 12. Efficacy of delgocitinib cream versus alitretinoin was assessed in all eligible randomly assigned patients who had available data at baseline, and safety was assessed in all patients exposed to trial treatment. The trial is registered with ClinicalTrials.gov (NCT05259722) and is complete. Findings: Between June 15, 2022, and Dec 5, 2023, 513 (334 [65%] female and 179 [35%] male) patients were randomly assigned to receive delgocitinib cream (n=254) or alitretinoin (n=259). Ten patients were excluded after randomisation due to not meeting eligibility criteria, so the full analysis set consisted of 250 patients in the delgocitinib group and 253 in the alitretinoin group. One patient in the delgocitinib group and three in the alitretinoin group were excluded from the primary analysis as they had missing HECSI data at baseline. A significantly greater least squares mean change in HECSI score from baseline to week 12 was observed with delgocitinib cream (-67·6 [SE 3·4]; n=249) versus alitretinoin (-51·5 [3·4]; n=250; difference -16·1 [95% CI -23·3 to -8·9], p<0·0001). Fewer patients reported adverse events in the delgocitinib group (125 [49%] of 253 patients) than in the alitretinoin group (188 [76%] of 247). The most frequent adverse events were headache (ten [4%] in the delgocitinib group vs 80 [32%] in the alitretinoin group), nasopharyngitis (30 [12%] vs 34 [14%]), and nausea (one [<1%] vs 14 [6%]). Interpretation: Delgocitinib cream showed superior efficacy and a more favourable safety profile versus oral alitretinoin over 24 weeks. These results support the benefit of delgocitinib cream in patients with severe chronic hand eczema. Funding: LEO Pharma.
Association of 24 h-movement behaviors with cerebral and hippocampal amyloid beta levels and executive function in cognitively normal older adults: a compositional data analysis from the AGUEDA trial
(Elsevier, 2025) Sclafani, Alessandro; Migueles, Jairo H.; Olvera-Rojas, Marcos; Solis-Urra, Patricio; Fernandez-Gamez, Beatriz; Coca-Pulido, Andrea; Bellón, Darío; Fernández-Ortega, Javier; Sanchez-Martinez, Javier; Sánchez-Aranda, Lucía; Toval, Ángel; Martín-Fuentes, Isabel; Bakker, Esmée A.; Gispert, Juan Domingo; Triviño-Ibañez, Eva M.; Liu-Ambrose, Teresa; Erickson, Kirk I.; Gomez-Rio, Manuel; Ortega, Francisco B.; Esteban-Cornejo, Irene
Objectives: This study investigated the associations between movement behaviors (physical activity, sedentary behavior, and sleep duration), global and hippocampal amyloid beta levels, and executive function in cognitively normal older adults. Design: Cross-sectional analysis using data from the Active Gains in brain Using Exercise During Aging study, including 86 participants (mean age 71.51 years, 57% female). Methods: Movement behaviors were assessed using a wrist-worn accelerometer over a 9-day. Amyloid beta levels were quantified via positron emission tomography, and executive function was assessed using validated cognitive tests (e.g., Trail Making Test, Digit Symbol Substitution Test, Spatial Working Memory test, and Dimensional Change Card Sort test). Compositional data analysis and multiple linear regression models were used to examine associations, adjusting for age, sex, education, and APOEε4 genotype status. Results: No significant associations emerged between any movement behaviors and total cerebral amyloid beta levels or executive function (all p > 0.05). However, higher moderate-to-vigorous physical activity was significantly associated with lower hippocampal amyloid levels in males (β = -0.039, p = 0.010), but not in females (β = 0.004, p = 0.741) (Moderate-to-vigorous physical activity × sex interaction p = 0.017). Conclusions: Movement behaviors were not associated with global amyloid levels or executive function. However, higher moderate-to-vigorous physical activity may be protective against hippocampal amyloid levels in older males. Further research is needed to confirm these findings and explore potential sex differences. These results underscore the importance of moderate-to-vigorous physical activity in brain health and suggest avenues for future research on the role of movement behaviors in amyloid burden.
Invited perspective: improving our approach to studies of outdoor artificial light at night and cancer risk
(American Chemical Society (ACS), 2026) Bhatti, Parveen; Kogevinas, Manolis
Comprehensive immunophenotyping of gastric adenocarcinoma identifies an inflamed class of tumors amenable to immunotherapies
(BMJ Publishing Group, 2025) Veas Rodriguez, Joel; Piñol, Miquel; Sorolla, Maria Alba; Parisi, Eva; Sorolla, Anabel; Santacana, Maria; Ruiz, Maria; Parra Farré, Genís; Bernabeu, Mario; Iglesias Coma, Mar; Aracil, Carles; Escartin, Alfredo; Vilardell, Felip; Matias-Guiu, Xavier; Salud, Antonieta; Montal, Robert
Background: Gastric adenocarcinoma (GAC) imposes a considerable global health burden. Molecular profiling of GAC from the tumor microenvironment perspective through a multi-omics approach is eagerly awaited in order to allow a more precise application of novel therapies in the near future. Methods: To better understand the tumor-immune interface of GAC, we identified an internal cohort of 82 patients that allowed an integrative molecular analysis including mutational profiling by whole-exome sequencing, RNA gene expression of 770 genes associated with immune response, and multiplex protein expression at spatial resolution of 34 immuno-oncology targets at different compartments (tumorous cells and immune cells). Molecular findings were validated in 595 GAC from the TCGA and ACRG external cohorts with available multiomics data. Prediction of response to immunotherapies of the discovered immunophenotypes was assessed in 1039 patients with cancer from external cohorts with available transcriptome data. Results: Unsupervised clustering by gene expression identified a subgroup of GAC that includes 52% of the tumors, the so-called Inflamed class, characterized by high tumor immunogenicity and cytotoxicity, particularly in the tumor center at protein level, with enrichment of PIK3CA and ARID1A mutations and increased presence of exhausted CD8+ T cells as well as co-inhibitory receptors such as PD1, CTLA4, LAG3, and TIGIT. The remaining 48% of tumors were called non-inflamed based on the observed exclusion of T cell infiltration, with an overexpression of VEGFA and higher presence of TP53 mutations, resulting in a worse clinical outcome. A 10-gene RNA signature was developed for the identification of tumors belonging to these classes, demonstrating in evaluated datasets comparable clinical utility in predicting response to current immunotherapies when tested against other published gene signatures. Conclusions: Comprehensive immunophenotyping of GAC identifies an inflamed class of tumors that complements previously proposed tumor-based molecular clusters. Such findings may provide the rationale for exploring novel immunotherapeutic approaches for biomarker-enriched populations in order to improve GAC patient's survival.
Rilzabrutinib in antihistamine-refractory chronic spontaneous urticaria: The RILECSU phase 2 randomized clinical trial
(American Medical Association, 2025) Giménez Arnau, Anna Maria; Ferrucci, Silvia M.; Ben-Shoshan, Moshe; Mikol, Vincent; Lucats, Laurence; Sun, Iris; Mannent, Leda P.; Gereige, Jessica
Importance: Chronic spontaneous urticaria (CSU) is a skin disease driven mainly by the activation of cutaneous mast cells through various mechanisms. Bruton tyrosine kinase (BTK), expressed in B cells and mast cells, plays a critical role in multiple immune-mediated disease processes. Objective: To determine the efficacy and risk profile of rilzabrutinib (SAR444671), an oral, reversible, covalent, next-generation BTK inhibitor, in treating patients with CSU. Design, setting, and participants: The Rilzabrutinib Efficacy and Safety in CSU (RILECSU) randomized clinical trial was a 52-week phase 2 study comprising a 12-week, double-blind, placebo-controlled, dose-ranging period, followed by a 40-week open-label extension. The trial was conducted from November 24, 2021, through April 23, 2024. Fifty-one centers enrolled and randomized participants across 12 countries in Asia, Europe, North America, and South America. The trial participants included adults aged 18 to 80 years with moderate to severe CSU (weekly Urticaria Activity Score [UAS7] of 16 or more; weekly Itch Severity Score [ISS7] of 8 or more) not adequately controlled with H1-antihistamine treatment. Interventions: Patients were randomized 1:1:1:1 to rilzabrutinib, 400 mg, once every evening (400 mg/d), twice per day (800 mg/d), 3 times per day (1200 mg/d), or matching placebo. Main outcomes: The primary end point was change from baseline at week 12 in ISS7 (for US and US reference countries) or UAS7 (for non-US reference countries). Results: A total of 160 omalizumab-naive and omalizumab-incomplete responders were randomized (mean [SD] age, 44.1 [13.4] years; 112 [70.0%] female). The primary analysis population included only the 143 omalizumab-naive patients. Significant reductions at week 12 were observed with rilzabrutinib, 1200 mg/d, vs placebo from baseline in ISS7 (least squares [LS] mean, -9.21 vs -5.77; difference, -3.44 [95% CI, -6.25 to -0.62]; P = .02) and UAS7 (LS mean, -16.89 vs -10.14; difference, -6.75 [95% CI, -12.23 to -1.26]; P = .02). In addition, improvements in weekly Hives Severity Score (HSS7) and weekly Angioedema Activity Score (AAS7) were observed. Improvements in ISS7, UAS7, HSS7, and AAS7 were observed as early as week 1. CSU-related biomarkers, including soluble Mas-related G protein-coupled receptor X2, immunoglobulin (Ig)-G antithyroid peroxidase, IgG anti-Fc-ε receptor 1, and interleukin-31, were reduced compared to placebo at week 12. Rilzabrutinib demonstrated a favorable risk-benefit profile; adverse events occurring at a higher frequency with rilzabrutinib vs placebo included diarrhea, nausea, and headache. Conclusions and relevance: The results of the RILECSU randomized clinical trial demonstrated efficacy and rapid onset of action of rilzabrutinib, 1200 mg/d, over 12 weeks, in addition to an acceptable adverse event profile. Together, these data support the use of rilzabrutinib in treating patients with moderate to severe CSU refractory to H1-antihistamines. Further research is needed to determine long-term efficacy and potential harms. Trial registration: ClinicalTrials.gov Identifier: NCT05107115.
Synbiotic intervention reverses alcohol drinking-induced cognitive deficits in adolescent male mice by modulating the microbiota-gut-brain axis
(Taylor & Francis, 2025) Barrera Conde, Marta; Korchevaya, Elizaveta; Kossatz de Mello, Elk, 1977-; Veza, Emma; Pujadas, Mitona; Alechaga, Élida; Nebot Forcada, Pau; Pozo Mendoza, Óscar J., 1975-; Torre Fornell, Rafael de la; Pizarro Lozano, Ma. Nieves; Robledo, Patricia, 1958-
Adolescence is characterized by an increased vulnerability to substance abuse, including alcohol consumption. We investigated the effects of a synbiotic intervention on disruptions of the microbiota-gut-brain axis induced by a drinking in the dark model of intermittent alcohol exposure in adolescent mice. We found that alcohol drinking induced specific shifts in gut microbiota, namely it increased Erysipelotrichaceae and reduced fecal butyric and isovaleric acids. In adulthood, other types of gut bacteria were affected such as Rhodospirillales uncultured family and Entrorhabdus uncultured bacterium. Social and nonsocial cognitive impairments were also observed, and disruptions in prefrontal cortex ß-hydroxybutyrate and glutamate metabolic profile in the hippocampus were apparent. Importantly, the synbiotic restored gut microbiota alterations and exerted beneficial effects on alcohol-induced behavioral impairments and brain metabolite changes. In correlational studies, we identified two potential functional networks, one relating gut microbiota (Actinobacteria and Lactobacillaceae)-isovaleric acid with prefrontal glutamate metabolism and sociability, and the other relating SCFAs (propionic, butyric, valeric and isovaleric acids) with ß-hydroxybutyrate in the hippocampus and reference memory. These results provide correlative data showing that synbiotic supplementation may restore delayed behavioral alterations induced by voluntary sub-binge alcohol drinking during adolescence through microbiota-gut-brain interactions, and might represent a potential therapeutic tool against long-term alcohol induced behavioral and molecular disturbances.
Prepandemic levels of cytokines and immunoglobulins and risk of SARS-CoV-2 infection and COVID-19 in the general population of Barcelona
(Frontiers, 2025) Porta, Miquel; Pumarega Rodríguez, José Antonio; Aguilar, Ruth; Prieto-Merino, David; Campi, Laura; Rius, Cristina; Villar García, Judit; Vidal, Marta; Jiménez, Alfons; Peña, Antonio; Muñoz Pérez, Miguel Ángel; Trasande, Leonardo; Bolúmar, Francisco; Moncunill, Gemma; Gasull Panadès, Magda; Dobaño, Carlota
Background: From a public health perspective it is remarkable that there are yet no longitudinal studies in the general population investigating the influence of the basal immune state, measured before the pandemic, on the risk of SARS-CoV-2 infection and COVID-19. Objective: To investigate the specific and combined effects of personal levels of cytokines and immunoglobulins-measured in individuals' blood 4 years before the pandemic-on the risk of SARS-CoV-2 infection and COVID-19 in a general population. Methods: We conducted a prospective cohort study in 240 individuals from the general population of Barcelona. Thirty cytokines and 31 immunoglobulins were quantified in prepandemic serum samples (collected in 2016-17) by high-throughput multiplex quantitative suspension array technology. Results: Higher concentrations in 2016-17 of IL-8 and TNF-α significantly decreased the risk of SARS-CoV-2 seropositivity in 2020-21, whereas higher concentrations of MIP-1α were a risk factor for seropositivity. Most cytokines in mixtures with IL-8, MIP-1α, TNF-α or G-CSF were associated with SARS-CoV-2 seropositivity (all OR ≥2.0 or OR≤0.4 and p < 0.05). The five individual isotype-antigen pairs more clearly associated with seropositivity were: protectively, IgG to CMV pp150, IgG to CMV pp65, and IgG to N OC43; and, increasing risk of seropositivity, IgM to CMV pp65 and IgM to EBV EA-D. The four cytokines most consistently associated with the risk of COVID-19 were also G-CSF, IL-8, TNF-α, and MIP-1α. The four isotype-antigen pairs more strongly associated with risk of COVID-19 (all protective) were IgA to CMV pp65 and N 229E, and IgG to EBV EAD and VCAp18. Conclusion: The unique longitudinal design of this study, with measurements before and during the pandemic in a general population, provides novel knowledge on the protective and detrimental effects of specific individual cytokines and immunoglobulins, and their mixtures, on the risk of SARS-CoV-2 seropositivity and COVID-19. If confirmed, findings would be significantly relevant for medicine and public health.
Tuberculosis household contact tracing in children: axes of inequality, Barcelona 2003-2022
(Frontiers, 2025) Prieto-García, Raquel; Millet, Joan-Pau; Soriano-Arandes, Antoni; Espiau, María; Broto, Claudia; Ronda, Mar; López, Núria; Noguera Julian, Antoni; Masdeu, Eva; Domingo Jimenez, Cristina; Ros Samsó, Miriam; Marcos Arroita, Maria Isabel; Ospina Valencia, Jesús Edison; García Rebollo, Carmen; Simon Viván, Pere; Rius Gibert, Cristina
Children under 15 years of age living in the household of a tuberculosis case constitute a very vulnerable group to tuberculosis infection (TBI). The objective of this study was to determine the prevalence of TBI and the risk factors associated with presenting TBI in this group, considering sex, age, and migratory status as axes of inequality. A population-based, analytical, cross-sectional observational study was carried out in the city of Barcelona in the period 2003-2022. The study population was household contacts under 15 years of age with index cases of pulmonary TB reported to the Barcelona Public Health Agency in the period 2003-2022. The analyses were performed using Generalized Estimating Equations (GEE) to predict the risk of TBI among these cohabiting contacts and were stratified considering the inequality axes of sex and migratory status. A total of 1084 contacts under 15 years of age were studied from 693 cases of tuberculosis. TBI prevalence among contacts was 24.5%. The factors associated with the presence of TBI in the contacts were having a smear positive in the index case, being older than 5 years in the contacts ([5,10], [10-15]) and the case and the contact being migrants; smear positive when the index case was native women and being from a municipal district with a lower incidence of tuberculosis when the index case was native women and the men. The results of the study confirm the importance of carrying out contact tracing and follow-up of household children, especially if the index case is smear positive. Contact tracing should be carried out as soon as possible to assess the prescription of primary chemoprophylaxis and TBI treatment to avoid rapid TB progression in children.
Neurocognitive and psychosocial functioning profiles in bipolar disorder and comorbid attention deficit hyperactivity disorder: a systematic review and meta-analysis
(Elsevier, 2025) Amoretti, Silvia; Amann, Benedikt Lorenz; Torrent, Carla
Bipolar disorder (BD) and attention deficit hyperactivity disorder (ADHD) are chronic psychiatric conditions with significant impacts on neurocognitive and psychosocial functioning. Co-occurrence of BD and ADHD (BD-ADHD) presents unique clinical challenges and could exacerbate cognitive and functional impairments. This systematic review and meta-analysis aimed to provide an updated synthesis of the differences in neurocognitive and psychosocial functioning between patients with BD-ADHD, BD, ADHD, and healthy controls (HC). A comprehensive systematic search identified 5639 records, with 34 studies meeting the inclusion criteria for a systematic review and 31 for the meta-analysis. There were no significant differences in cognitive performance across none of the evaluated cognitive domains between BD-ADHD and BD patients. BD-ADHD patients exhibited significantly lower visual memory (SMD=-0.29, 95 % CI=-0.53,-0.04; p = 0.022) compared to ADHD patients. Compared to HC, BD-ADHD patients showed poorer performance in processing speed (SMD=-0.54, 95 % CI= -0.86,-0.22; p < 0.001), sustained attention (SMD=-0.40, 95 % CI=-0.62, -0.19; p < 0.001), visual memory (SMD=-0.47, 95 % CI=-0.69,-0.26; p < 0.001), working memory (SMD=-0.79, 95 % CI=-1.13,-0.44; p < 0.001), cognitive flexibility and higher-order executive functions (SMD=-0.52, 95 % CI=-0.84,-0.20; p = 0.001), and verbal memory (SMD=-0.95, 95 % CI=-1.43,-0.47; p < 0.001). Psychosocial functioning was significantly worse in BD-ADHD patients compared to BD (SMD=-0.46; p < 0.001), ADHD (SMD=-1.00; p < 0.001), and HC (SMD=-3.54; p < 0.001). Our results suggest that the co-occurrence of BD and ADHD is associated with significant neurocognitive and psychosocial impairments. These findings underscore the need for targeted interventions to address the unique challenges of this comorbid condition, informing clinical practice and guiding future research.
Drug-drug interactions in metastatic hormone-sensitive prostate cancer (mHSPC): practical considerations for treating men with androgen receptor pathway inhibitors and common medications in this stage
(Taylor & Francis, 2025) Ibáñez, Cristina; Tourís-Lores, Manuel; Montesa, Álvaro; López-Campos, Fernando; Ríos, Emilio; Usán, Paola; Moretones, Cristina; Conde Estévez, David
Introduction: New androgen receptor pathway inhibitors (ARPIs) are an essential part of the treatment strategy for patients with metastatic hormone-sensitive prostate cancer (mHSPC). Despite the good tolerability of ARPIs, after treatment is started, drug-drug interactions (DDIs) between these and other medications frequently taken by these patients may appear. DDIs may reduce the therapeutic effect of both and lead to increased adverse events. DDIs should be carefully assessed before an ARPI is started. Areas covered: We first review the current therapeutic landscape for mHSPC, common age-related comorbidities and other comorbidities or adverse events arising from previous or current treatments for prostate cancer, and patients' symptomatology. We then analyze the potential toxicities arising from medications for these conditions and those of mHSPC: ARPIs (abiraterone acetate plus prednisone/prednisolone, enzalutamide, apalutamide, and darolutamide) and docetaxel. Expert opinion: Before mHSPC patients are treated with an ARPI, careful assessment of patient eligibility for each treatment alternative and potential DDIs between these and treatments for current comorbidities is a fundamental component in clinical decision-making. ARPIs with low potential DDIs allow keeping current concomitant medications without significant relevant dose adjustments and help reduce the risk of toxicities and comorbidity-related decompensation.
Preoperative estimation of the pathological breast tumor size in architectural distortions: a comparison of DM, DBT, US, CEM, and MRI
(Springer, 2025) Azcona Sáenz, Javier; Molero Calafell, Javier; Román, Marta; Vall, Elisenda; Comerma Blesa, Laura, 1983-; Alcantara Souza, Rodrigo; Vernet-Tomás, Maria
Objective: This study aims to compare the accuracy of digital mammography (DM), digital breast tomosynthesis (DBT), ultrasound (US), magnetic resonance imaging (MRI), and contrast-enhanced mammography (CEM) in the preoperative evaluation of breast cancer size in architectural distortions (ADs). Additionally, it assesses whether including thin spicules in mammography measurements affects accuracy. Materials and methods: We planned a retrospective analysis of invasive breast cancers presenting as ADs in our breast screening program between 2018 and 2022. Tumor size was measured in mm using DM, DBT, US, MRI, and CEM. Measurements were compared to the surgical specimen sizes. Two measurement approaches for DM and DBT were applied, considering and not considering thin spicules. T-student test was used to compare mean sizes across imaging techniques with the surgical specimen. Results: The study encompassed 59 female patients with 63 ADs. Mean age was 60.1 years (Standard Deviation (SD): 6.3). The cancers included four histological subtypes, ductal (69.8%), lobular (23.8%), tubular (4.8%), and micropapillary (1.6%). All imaging techniques, except for US (mean: 12.4 mm, SD: 5.7), overestimated tumor size compared to histology (mean: 16.40 mm, SD: 9). CEM, MRI, and DBT without thin spicules closely matched histological size. Including thin spicules in DM and DBT led to overestimation. Concordance was highest with CEM (75%) and MRI (67.6%). No significant differences were found between ductal and lobular carcinoma. Conclusion: For preoperative tumor size estimation of breast cancer in ADs, DBT excluding thin spicules, CEM, and MRI seemed most accurate. Including thin spicules in mammography leads to overestimation. Key Points: Question Identifying the most accurate imaging technique for preoperative tumor staging of architectural distortions (ADs) is crucial now that contrast-enhanced mammography (CEM) is widely implemented. Findings Measuring thin wispy spicules in ADs on digital (DM) and digital breast tomosynthesis (DBT) should be avoided, as they consistently overestimate pathological tumor stage. Clinical relevance Precise tumor size estimation in ADs is critical for proper staging and treatment planning. This study favors the use of DBT excluding thin spicules, CEM, and magnetic resonance imaging (MRI) for optimal accuracy.
Biomarkers of palbociclib response in hormone receptor-positive advanced breast cancer from the PARSIFAL trial
(Nature Research, 2025) Albanell Mestres, Joan; Gamez-Pozo, Angelo; Arteaga, Carlos L.; Bellet, Meritxell; Rojo, Federico; González, Abel; Bellosillo Paricio, Beatriz; Serra, Violeta; Gener, Petra; Guerrero, José A.; Shimizu, Eileen; Mancino, Mario; Rodríguez-Morató, Jose, 1987-; Mina, Leonardo; Pérez-García, José Manuel; Cortés, Javier; Llombart-Cussac, Antonio
Currently, there are no clinically actionable biomarkers to predict patient to cyclin-dependent kinases 4 and 6 inhibitors (CDK4/6i) plus endocrine therapy for hormone receptor (HR)[+]/ human epidermal growth factor receptor 2 (HER2)[-] advanced breast cancer (ABC). Herein, we report an exploratory biomarker substudy (transFAL) from a subset of patients included in PARSIFAL, a phase II randomized clinical trial that evaluated first-line palbociclib plus fulvestrant or letrozole for HR[+]/HER2[-] ABC. No definitive biomarkers were discovered, however, worse outcomes were found with CDK6 postivity (p = 0.008), ER negativity (p = 0.008), high Ki67 (p = 0.04), and TP53 mutation (p = 0.04). ctDNA density (p = 0.036) and number of mutations (p = 0.033) at baseline were significantly higher for resistant patients. Our study reveals future directions to explore in the goal to determine biomarkers of response to CDK4/6i.
Association between muscle strength and echogenicity using greyscale ultrasound software: a diagnostic accuracy study in kidney transplant candidates
(Edizione Minerva Medica, 2025) Acuña-Pardo, Carolina; Muñoz Redondo, Elena; Delcros-Forestier, Lou; Curbelo Peña, Yulibeth; Rodríguez-Hernández, Carlos; Meza Valderrama, Delky; Sánchez-Rodríguez, Dolores; Pascual, Julio (Pascual Santos); Pérez-Sáez, María José; Marco Navarro, Ester
Background: Advanced chronic kidney disease disrupts the delicate equilibrium between protein anabolism and catabolism, leading to alterations in muscle quantity, quality, and function. Musculoskeletal ultrasound emerges as a promising assessment tool due to its widespread availability and high reliability. Aim: To evaluate the efficacy of rectus femoris (RF) echogenicity, measured using greyscale software, in identifying diminished muscle quality and strength in candidates for kidney transplant. Design: Post-hoc diagnostic accuracy study. Setting: Outpatients in a multimodal prehabilitation program pre kidney transplantation (KT). Population: Patients on the waiting list for KT. Methods: Sensitivity, specificity, likelihood ratios and area under the curve (AUC) for diagnostic efficacy of echogenicity (index test) assessed with the ImageJ software greyscale as a potential marker of quadriceps muscle weakness (reference test) were calculated. Muscle weakness was considered as maximal voluntary isometric contraction of the quadriceps (Q-MVIC) <40% of body weight. Other variables included body composition parameters derived from multifrequency electrical bioimpedance, upper limb muscle strength (handgrip), and RF thickness assessed by ultrasound. Statistical tests: Chi-square, t-Student, Pearson correlation coefficients (r), bivariate and multivariate logistic regression models. Statistical significance level ≤0.05. Results: Of 112 patients (mean age: 63.6, 76% male), 72 (63.7%) exhibited quadriceps weakness, while 80 (70.8%) had some degree of overhydration (extracellular water/total body water ratio >0.390). The echogenicity cut-off point of highest concordance with muscle weakness was 70, boasting a sensitivity of 83%, specificity of 57%, and AUC of 0.671 (CI 95% 0.570-0.772 [P=0.003]). Echogenicity >70 was associated with a 3.4-fold higher risk of muscle weakness (crude OR = 3.4 [CI95% 1.4 to 8.0]), which persisted after adjusting for age, height, weight and RF thickness. Conclusions: The RF echogenicity exhibits fair validity in identifying muscle weakness among candidates for KT. However, it cannot be endorsed as a standalone diagnostic tool in this population. Clinical rehabilitation impact: Early identification of muscle weakness would advance efforts to mitigate morbidity and mortality through targeted measures.
Local anaesthesia and pain management in image-guided breast interventions: empathy in action
(Elsevier, 2025) Alcantara Souza, Rodrigo; Arenas, Natalia; Azcona Sáenz, Javier; Pitarch, Mireia; Vall, Elisenda; Vila-Trias, Elisabet; Ejarque, Belén; Maiques Llácer, José María; Montes Pérez, Antonio
Effective pain management is critical in image-guided breast interventions, directly contributing to patient comfort and procedural success. This review provides breast radiologists with actionable insights into pain mechanisms, the optimisation of local anaesthetic delivery, and practical supplementary methods to minimise injection discomfort. Evidence-based techniques, including buffering, warming of solutions, and the addition of vasoconstrictors, are explored. Pharmacological properties, safety considerations, and innovative approaches, including patient-centred care and anxiety management strategies, are also discussed. Together, these considerations form a comprehensive framework to advance practices and elevate the standard of care in breast interventions.
Comorbidities are associated with unfavorable outcome in aquaporin-4 antibody positive neuromyelitis optica spectrum disorders and myelin oligodendrocyte glycoprotein antibody-associated disease: exploratory study from the CROCTINO cohort
(Wiley, 2025) Samadzadeh, Sara; Villoslada, Pablo; Asgari, Nasrin
Background: Comorbidities occur in aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and double seronegative NMOSD (DN-NMOSD), potentially contributing to a less favorable disease course. Objectives: To characterize comorbidities in AQP4-NMOSD, MOGAD, and DN-NMOSD and assess their association with optic neuritis (ON) outcomes by optical coherence tomography (OCT) in AQP4-NMOSD. Methods: Four hundred and forty-two participants from the CROCTINO cohort were evaluated for comorbidities. Results: In AQP4-NMOSD patients (n = 360), 43.5% (n = 161) had comorbidities, equally divided between single and multiple. In MOGAD (n = 49), 40.8% had comorbidities, with 75% (n = 15) single and 25% (n = 5) multiple. In DN-NMOSD (n = 33), 36.4% (n = 12) had comorbidities equally split. AQP4-NMOSD patients had more multiple comorbidities (50%, n = 81/161) than MOGAD (25%, n = 5/20, p = 0.03) and more autoimmune disorders (AID) (40.4%, n = 65) than MOGAD (20%, n = 4, p = 0.09) and DN-NMOSD (none, p = 0.004). Cardiovascular comorbidities and related risk factors (CVC/RF) occurred in 34.8% (n = 56) of AQP4-NMOSD, 50% (n = 10) of MOGAD, and 33.3% (n = 4) of DN-NMOSD. Expanded Disability Status Scale was higher in MOGAD (3.0 vs. 2.0, p = 0.006) and DN-NMOSD (5.0 vs. 2.0, p = 0.008) with comorbidities. AQP4-NMOSD patients with CVC/RF had higher ON relapse rates than those with AID (1.06 ± 3.33 vs. 0.49 ± 0.98, p < 0.001). OCT revealed reduced inner nuclear layer thickness in AQP4-NMOSD with comorbidities compared to non-comorbidity (B = -1.52, p = 0.047), more pronounced with CVC/RF (B = -2.96, p = 0.009). Conclusion: Comorbidities are frequent in AQP4-NMOSD and MOGAD and are associated with ON frequency and disability. These findings highlight the need for proactive comorbidity management to improve patient care.
Biomarkers in gastroesophageal cancer 2025: an updated consensus statement by the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Pathology (SEAP)
(Springer, 2025) Alsina Maqueda, Maria; Teijo Quintáns, Ana; Cuatrecasas, Miriam; Fernández Aceñero, María Jesús; Fernández Montes, Ana; Gómez Martín, Carlos; Jiménez Fonseca, Paula; Martínez Ciarpaglini, Carolina; Rivera Herrero, Fernando; Iglesias Coma, Mar
Gastroesophageal carcinomas, including gastroesophageal adenocarcinoma (GEA) and esophageal squamous cell carcinoma (ESCC), pose a global health challenge due to their heterogeneity. The approach to diagnosis and treatment should first differentiate between GEA and ESCC. Over the past decade, therapies for metastatic or advanced GEA/ESCC have expanded, with several new therapeutic targets alongside trastuzumab for metastatic HER2-positive GEA. Four key biomarkers are essential for targeted therapy: HER2 overexpression/amplification, deficient mismatch repair/microsatellite instability (dMMR/MSI), PD-L1, and Claudin18.2 expression. Immunohistochemistry is the recommended method for these biomarkers evaluation. In addition, the assessment of biomarkers like FGFR2b is likely to become routine in the near future. Experts from the Spanish Society of Pathology (SEAP) and the Spanish Society of Medical Oncology (SEOM) have formed a consensus to optimize biomarker detection and usage in clinical practice. Their recommendations aim to improve personalized treatment strategies for GEA and ESCC patients, integrating new diagnostic insights into routine care.
Emergency inguinal hernia surgery: a proposed update to the clinical guidelines algorithm
(Elsevier, 2025) Rodrigues Gonçalves, Victor; Verdaguer-Tremolosa, Mireia; Bravo-Salva, Alejandro; Martínez-López, Pilar; Pereira Rodríguez, José Antonio; López Cano, Manuel
Introduction: Management strategies for acute irreducible hernias vary, with recent debates on the role of manual reduction versus immediate surgery. This study aimed to identify preoperative risk factors for bowel resection in acute irreducible inguinal hernias. Methods: A retrospective cohort study included patients from 2 university hospitals who underwent emergency surgery for acute irreducible hernias between January 2010 and December 2018. Results: Out of a total of 652 patients, 15% required intestinal resection; females, older individuals, and those with comorbidities were more likely to undergo resection. Multivariate analysis identified patients with femoral hernia (OR 2.272; 95%CI 1.275-4.047; P = .005) and preoperative intestinal obstruction (OR 8.071; 95%CI 4.331-15.043; P < .001). Patients needing resection experienced higher postoperative complication rates and longer hospital stays. Discussion: Femoral hernia and preoperative intestinal obstruction were independent predictors of bowel resection in acute irreducible hernias. Incorporating these factors into decision-making algorithms may improve patient outcomes and optimize surgical management.
Biomarkers to predict therapeutic response in chronic spontaneous urticaria: a review
(John Libbey Eurotext, 2024) Giménez Arnau, Anna Maria; Salman, Andaç; Podder, Indrashis
Chronic spontaneous urticaria (CSU) is a relatively common dermatological disorder characterized by sudden and unpredictable onset of pruritic wheals and/or angioedema, for more than six weeks. It is a mast cell-mediated histaminergic disorder, considerably worsening patients' quality of life. Current treatment options include anti-histamines, omalizumab and cyclosporine, in a step-wise algorithmic approach, aimed at complete symptom control. Patients do not respond uniformly to these therapeutic options due to phenotypic and endotypic heterogeneity, and often remain uncontrolled/poorly controlled. Recent research is focused on identifying certain biomarkers to predict therapeutic response and facilitate patient-targeted personalized treatment, for maximum benefit. The current article summarizes various biomarkers explored to date, and also elaborates their role in predicting therapeutic response to anti-histamines, omalizumab and cyclosporine, in CSU patients. High disease activity, elevated CRP/ESR and elevated D-dimer are the most important predictors of non/poor-response to antihistamines. Low and very low baseline IgE, elevated CRP/ESR, ASST+, BAT/BHRA+, basopenia, eosinopenia, and elevated D-dimer are predictors of poor and good response to omalizumab and cyclosporine, respectively. Additionally, normal or slightly elevated baseline IgE and FceR1 overexpression are predictors of a faster response with omalizumab. However, none of these predictors have so far been completely validated and are not yet recommended for routine use. Thus, large-scale prospective studies are needed to confirm these predictive biomarkers and identify new ones to achieve the goal of personalized medicine for CSU.

Navigate

Browse

Recent Submissions