Hospital del Mar Research Institute
L'Hospital del Mar Research Institute és un centre d'excel·lència per a la recerca biomèdica i sanitària. Forma part de l’Hospital del Mar, i està format per més de 700 professionals, amb una composició mixta d'investigadors de l'Institut de Recerca i investigadors clínics de l'Hospital del MAR i altres investigadors de la Universitat Pompeu Fabra (UPF), la Universitat Autònoma de Barcelona (UAB) i la Fundació BarcelonaBeta Brain Research Center (BBRC).
URI permanent per a aquesta comunitat http://hdl.handle.net/10230/23115
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Item type: Item , 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, MichaelThe 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.Item type: Item , 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, ErnestThe 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.Item type: Item , Evidence-based personalised medicine in critical care: a framework for quantifying and applying individualised treatment effects in patients who are critically ill(Elsevier, 2025) Munroe, Elizabeth S.; Castellví Font, Andrea; Goligher, Ewan C.Clinicians aim to provide treatments that will result in the best outcome for each patient. Ideally, treatment decisions are based on evidence from randomised clinical trials. Randomised trials conventionally report an aggregated difference in outcomes between patients in each group, known as an average treatment effect. However, the actual effect of treatment on outcomes (treatment response) can vary considerably between individuals, and can differ substantially from the average treatment effect. This variation in response to treatment between patients-heterogeneity of treatment effect-is particularly important in critical care because common critical care syndromes (eg, sepsis and acute respiratory distress syndrome) are clinically and biologically heterogeneous. Statistical approaches have been developed to analyse heterogeneity of treatment effect and predict individualised treatment effects for each patient. In this Review, we outline a framework for deriving and validating individualised treatment effects and identify challenges to applying individualised treatment effect estimates to inform treatment decisions in clinical care.Item type: Item , 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, AndreaBackground: 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.Item type: Item , Involvement of microRNAs-449/FASN axis in response to trastuzumab therapy in HER2-positive breast cancer(BioMed Central, 2025) Lameirinhas, Ana; Torres-Ruiz, Sandra; Garrido-Cano, Iris; Hernando, Cristina; Martínez, María Teresa; Rovira, Ana; Albanell Mestres, Joan; Zazo, Sandra; Rojo, Federico; Bermejo, Begoña; Lluch, Ana; Cejalvo, Juan Miguel; Tormo, Eduardo; Eroles, PilarThe anti-HER2 monoclonal antibody trastuzumab and new derivative formulations are the standard treatment for HER2-positive breast cancer. However, after 1 to 5 years of treatment, some patients acquire resistance to therapy, leading to relapse. The microRNA-449 family members were downregulated in HER2-positive breast cancer cell lines and low levels were associated with patients¿ worse prognosis. Moreover, trastuzumab-resistant HER2-positive breast cancer cell lines showed lower microRNAs-449 and higher Fatty Acid Synthase (FASN) expression, compared to sensitive cell lines. The direct regulation of FASN by microRNA-449a and microRNA-449b-5p was demonstrated. Moreover, microRNAs-449 overexpression and FASN inhibition decreased cell proliferation and sensitized cells to trastuzumab treatment by inhibiting the PI3K/AKT signaling pathway. Together, these results suggest the microRNAs-449/FASN axis as a potential therapeutic target in combination with anti-HER2 agents to overcome trastuzumab resistance and to improve treatment response in HER2-positive breast cancer patients.