Scientia, Dipòsit d’Informació Digital del Departament de Salut
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C-reactive protein expression in acute ischemic stroke blood clots: Implications for etiology
Get PDFStroke; Etiology; InflammationAccident cerebrovascular; Etiologia; InflamacióAccidente cerebrovascular; Etiología; InflamaciónIntroduction: C-reactive protein (CRP) is a prototypic inflammation marker, with elevated levels associated with an increased risk of cerebrovascular events. To determine whether CRP could be a useful biomarker of stroke etiology, we investigated CRP expression in acute ischemic stroke (AIS) clots from large-artery atherosclerosis (LAA), cardio-embolism (CE) and cryptogenic (Crypt) subtypes.
Patients and methods: We analysed clot samples from AIS patients (LAA, CE, Crypt; n = 50 each), collected across five stroke centres in France, Serbia, Spain, and Japan between February 2021 and February 2024, as part of the prospective Clotbase International Registry of 460 patients who underwent mechanical thrombectomy. Clot components were assessed using Martius Scarlet Blue staining. CRP expression was examined using immunohistochemistry and its co-localisation with clot components was detected using immunofluorescence. Clinical parameters were compared across etiologies.
Results: CRP expression varied significantly among clots. Most clots (65%) had minimal (⩽1%) CRP and 35% showed substantial (>1%) CRP. CE group had significantly more clots with substantial CRP than LAA and Crypt (48% vs 30% and 26%; p = 0.048). Clots with substantial CRP contained more fibrin (28.9%) than those with low CRP (20.6%; p = 0.005). Confocal microscopy showed CRP co-localised with fibrin and white blood cells (WBCs).
Discussion and conclusion: Significantly more AIS clots of CE expressed substantial CRP compared to those of LAA and Crypt, suggesting CE strokes may be more strongly linked to inflammation. Clots with substantial CRP expression displayed significantly more fibrin compared to those with minimal CRP expression, suggesting a potential association between inflammation and fibrin-rich clots. Further study of the relationship between CRP, fibrin and WBCs in clots may improve our understanding of the processes of thrombo-inflammation.The funders and award number are Research Ireland: 13/RC/2073_2 and Sensome; Chinese Scholarship Council
Non-relapse mortality with bispecific antibodies: A systematic review and meta-analysis in lymphoma and multiple myeloma
Get PDFCAR T-cell therapy; Bispecific antibodies; LymphomaTeràpia amb cèl·lules T CAR; Anticossos biespecífics; LimfomaTerapia con células T CAR; Anticuerpos biespecíficos; LinfomaBispecific antibodies (BsAb) are associated with distinct immune-related toxicities that impact morbidity and mortality. This systematic review and meta-analysis examined non-relapse mortality (NRM) with BsAb therapy in B-cell non-Hodgkin lymphoma (NHL) and multiple myeloma (MM). A PubMed and Embase search up to October 2024 identified 29 studies (21 NHL, 8 MM) involving 2,535 patients. The overall NRM point estimate was 4.7% (95% confidence interval [CI] 3.4%-6.4%), with a median follow-up of 12.0 months. We noted no significant difference in NRM across disease entities (NHL: 4.2%, MM: 6.2%, p = 0.22). In NHL, prespecified subgroup analyses revealed increased NRM in real-world studies compared to clinical trials. For MM, an association between NRM and higher response rates and longer follow-up was noted. Meta-regression comparing BsAb and CAR-T therapies (n = 8,592) showed no significant NRM difference when accounting for key study-level confounders (p = 0.96). Overall, infections were the leading cause of NRM, accounting for 71.8% of non-relapse deaths. Of the infection-related deaths, 48% were attributed to COVID-19. In a pre-specified sensitivity analysis excluding COVID-19 fatalities, the overall NRM estimate was 3.5% (95% CI 2.6%-4.6%). Taken together, these results provide a benchmark for the estimated NRM with BsAb therapy and highlight the paramount importance of infection reporting, prevention, and mitigation
In utero therapy for spinal muscular atrophy: closer to clinical translation
Get PDFIn-utero therapy; Fetus; Gene therapyTeràpia intrauterina; Fetus; Teràpia gènicaTerapia intrauterina; Feto; Terapia génica5q-Spinal muscular atrophy (SMA) has been a trailblazer in the development of advanced therapies for inherited diseases. SMA is an autosomal recessive disorder affecting mainly motor neurons in the anterior horn of the spinal cord and brainstem motor nucle but currently considered a systemic disease. Advances in understanding the genetics of SMA led to the development of disease-modifying therapies, either transferring a healthy version of SMN1, the causative gene absent or altered in SMA, or modulating SMN2, a highly homologous but less functional version of SMN1, present in all patients. After successful clinical trials, these approaches have resulted in three marketed therapies. Severe SMA, ‘type I’, is the most common type and is considered both a developmental arrest and neurodegenerative disorder. As pathology starts during fetal life in type I patients, a cure is unlikely even when treatment is started shortly after birth in the pre- or mildly symptomatic state. In utero fetal therapy offers the opportunity to mitigate further or possibly prevent manifestations of the disease.
This review discusses clinical and developmental aspects of SMA, the advanced therapies approved (gene therapy, antisense oligonucleotide and small molecule compounds), and the rationale, options and challenges, including ethical and safety issues, to initiate in utero therapy. Looking beyond sporadic case reports of prenatal intervention, clinical trials of in utero SMA therapy can be envisaged and should be carefully designed and evaluated to move closer to clinical translation.G.L. was supported by the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant (H2020 Marie Skłodowska-Curie Actions) agreement no. 9561859 (SMABEYOND ITN to E.F. T.)
La atrofia muscular espinal
Get PDFAtròfia muscular espinal; Cribratge neonatal; Prova del talóAtrófia muscular espinal; Cribado neonatal; Prueba del talónSpinal muscular atrophy; Newborn screening; Heel prick testAquest document, adreçat a les famílies, ofereix informació bàsica sobre l’atròfia muscular espinal en nadons: en què consisteix, com es detecta, com cal actuar amb rapidesa i quines opcions de tractament existeixen.Este documento, dirigido a las familias, ofrece información básica sobre la atrofia muscular espinal en bebés: en qué consiste, cómo se detecta, cómo actuar con rapidez y qué opciones de tratamiento existen.This document, intended for families, provides basic information about spinal muscular atrophy in infants: what it is, how it is detected, how to act quickly, and what treatment options are available
Insights on Oligometastatic Non-Small-Cell Lung Cancer
Get PDFBiomarkers; Immunotherapy; Local ablative therapiesBiomarcadors; Immunoteràpia; Teràpies ablatives localsBiomarcadores; Inmunoterapia; Terapias ablativas localesOligometastatic non-small-cell lung cancer (OMD-NSCLC) has emerged as a biologically and clinically distinct subtype of advanced disease, characterized by limited metastatic burden and a more indolent course. In this narrative review, we examine the current definition of OMD-NSCLC, diagnostic tests, possible biomarkers, and current therapeutic strategies. Biological insights highlight the role of microRNAs in differentiating true oligometastatic state from polymetastatic disease. The main local ablative therapies (LAT) include surgery and radiotherapy. The integration of LAT with systemic therapies has been explored in clinical trials, yielding promising but occasionally inconsistent results. As the therapeutic landscape of OMD-NSCLC patients continues to evolve, refining definitions, identifying predictive biomarkers, and individualizing care are essential steps toward achieving the potential of radical-intent therapy
Actualització del marc estratègic i full de ruta (2022-24) del Pla director de salut mental i addiccions
Get PDFSalut mental; Addiccions; SMiA; Planificació sanitàriaMental health; Addictions; Health planningSalud mental; Adicciones; Planificación sanitariaL’Actualització del marc estratègic i full de ruta (2022-24) del Pla director de salut mental i addiccions (PDSMiA) reafirma l’objectiu d’integrar funcionalment les xarxes de salut mental d’adults, infantil i la xarxa de drogodependències. Aquesta integració és clau per millorar la coordinació entre dispositius i garantir una atenció més eficient i centrada en la persona. El Pla de salut 2021-2025 també subratlla la necessitat d’enfortir la connexió entre els Centres de Salut Mental d’Adults (CSMA) i els Centres d’Atenció i Seguiment (CAS), especialment en casos complexos com la patologia dual o el consum problemàtic en menors, que sovint requereixen serveis de totes dues xarxes. Els beneficis esperats inclouen una major continuïtat assistencial, reducció de duplicitats i eliminació d’exclusions en la intervenció. Operativament, això implica establir circuits comuns, protocols compartits i mecanismes que assegurin la col·laboració entre professionals i dispositius. L’actualització del PDSMiA aposta per una visió integrada que permeti abordar la salut mental i les addiccions de manera global, amb un enfocament preventiu i assistencial que respongui a les necessitats reals de la població.La Actualización del marco estratégico y hoja de ruta (2022-24) del Plan director de salud mental y adicciones (PDSMiA) reafirma el objetivo de integrar funcionalmente las redes de salud mental de adultos, infantil y la red de drogodependencias. Esta integración es clave para mejorar la coordinación entre dispositivos y garantizar una atención más eficiente y centrada en la persona. El Plan de salud 2021-2025 subraya también la necesidad de fortalecer la conexión entre los Centros de Salud Mental de Adultos (CSMA) y los Centros de Atención y Seguimiento (CAS), especialmente en casos complejos como la patología dual o el consumo problemático en menores, que a menudo requieren servicios de ambas redes. Los beneficios esperados incluyen una mayor continuidad asistencial, reducción de duplicidades y eliminación de exclusiones en la intervención. Operativamente, esto implica establecer circuitos comunes, protocolos compartidos y mecanismos que aseguren la colaboración entre profesionales y dispositivos. La actualización del PDSMiA apuesta por una visión integrada que permita abordar la salud mental y las adicciones de forma global, con un enfoque preventivo y asistencial que responda a las necesidades reales de la población.The Update of the Strategic Framework and Roadmap (2022-24) of the Mental Health and Addictions Master Plan (PDSMiA) reaffirms the objective of functionally integrating the adult, child and drug addiction mental health networks. This integration is key to improving coordination between devices and ensuring more efficient and person-centered care. The 2021-2025 Health Plan also emphasizes the need to strengthen the connection between Adult Mental Health Centers (CSMA) and Care and Monitoring Centers (CAS), especially in complex cases such as dual pathology or problematic consumption in minors, which often require services from both networks. The expected benefits include greater continuity of care, reduction of duplication and elimination of exclusions in intervention. Operationally, this involves establishing common circuits, shared protocols and mechanisms that ensure collaboration between professionals and devices. The update of the PDSMia is committed to an integrated vision that allows mental health and addictions to be addressed globally, with a preventive and care approach that responds to the real needs of the population
Per què m’he de vacunar contra la grip? Personal de centres sanitaris
Get PDFVacunació antigripal; Vacunació contra la grip; Rebuig a la vacunacióFlu vaccination; Healthcare workers; Refusal to vaccinationVacunación antigripal; Vacunación contra la gripe; Rechazo a la vacunaciónDocument amb arguments per aconsellar la vacunació de la grip. Consells i recomanacions destinats als professionals sanitaris.Documento con argumentos para aconsejar la vacunación de la gripe. Consejos y recomendaciones destinados a los profesionales sanitarios.Arguments to advise flu vaccination. Advice and recommendations for health professionals
Intracranial activity of sotorasib vs docetaxel in pretreated KRAS G12C-mutated advanced non-small cell lung cancer from a global, phase 3, randomized controlled trial
Get PDFBrain metastases; Non-small cell lung cancer; SotorasibMetàstasis cerebrals; Càncer de pulmó de cèl·lules no petites; SotorasibMetástasis cerebrales; Cáncer de pulmón de células no pequeñas; SotorasibObjectives
To assess the efficacy and safety of sotorasib in patients with brain metastases using data from the phase 3 CodeBreaK 200 study, which evaluated sotorasib in adults with pretreated advanced or metastatic KRAS G12C-mutated non-small cell lung cancer (NSCLC).
Materials and methods
Patients with KRAS G12C-mutated NSCLC who progressed after platinum-based chemotherapy and checkpoint inhibitor therapy were randomized 1:1 to sotorasib or docetaxel. An exploratory post-hoc analysis evaluated central nervous system (CNS) progression-free survival (PFS) and time to CNS progression in patients with treated and stable brain metastases at baseline. Measures were assessed by blinded independent central review per study-modified Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria.
Results
Of the patients randomly assigned to receive sotorasib (n=171) or docetaxel (n=174), baseline CNS metastases were present in 40 (23%) and 29 (17%) patients, respectively. With a median follow-up of 20.0 months for this patient subgroup, median CNS PFS was longer with sotorasib compared with docetaxel (9.6 vs 4.5 months; hazard ratio, 0.43 [95% CI, 0.20–0.92]; P=0.02). Among patients with baseline treated CNS lesions of ≥10 mm, the percentage of patients who achieved CNS tumor shrinkage of ≥30% was two-fold higher with sotorasib than docetaxel (33.3% vs 15.4%). Treatment-related adverse events among patients with CNS lesions at baseline were consistent with those of the overall study population.
Conclusions
These results suggest intracranial activity with sotorasib complements the overall PFS benefit observed with sotorasib vs docetaxel, with safety outcomes similar to those in the general CodeBreaK 200 population.
Clinical trials registration number: NCT04303780.Representatives of the sponsor, Amgen Inc., designed the clinical study in collaboration with some of the study investigators. Amgen Inc. managed patient data collection at the study sites, maintained the study database, performed the analyses, funded medical writing support, paid publication costs, and paid the open access charge for this article
Ultrasound-Guided Botulinum Toxin Infiltrations in Essential Tremor Patients: A 36-week Follow Up
Get PDFBotulinum toxin; Essential tremor; Ultrasound-guided injectionToxina botulínica; Tremolor essencial; Infiltració guiada per ecografiaToxina botulínica; Temblor esencial; Infiltración guiada por ecografíaEssential tremor (ET) presents therapeutic challenges as oral therapies, are often partially effective and carry adverse effects. Deep Brain Stimulation and High-intensity Focused Ultrasound targeting the ventral intermediate thalamic nucleus show efficacy in managing ET; however, their cost and invasiveness deter some patients. Botulinum toxin infiltrations for ET in the upper limbs have been limited by adverse effects. Most studies used manual or electromyography guidance, while ultrasound guidance has been less explored. The purpose of the present study was to investigate the potential long-term improvement in tremor and quality of life among ET patients following ultrasound-guided IncobotulinumtoxinA (IncoBoNT) infiltrations.
We present 18 ET patients who received IncoBoNT injections guided by ultrasounds. We also propose an anatomo-physiological paradigm for targeting muscles in ET patients based on two different tremor patterns.
Eighteen ET patients (mean age 68.2 years) were followed over 12 months. After 36 weeks, patients with supination/pronation (SPP) and flexion/extension (FEP) patterns showed significant TETRAS score improvements: 46.4% in SPP (p = 0.0022) and 48.2% in FEP (p = 0.0021). The QUEST-QOL score also improved (65% in SPP, p = 0.0018; 62.7% in FEP, p = 0.0018). All patients presented notable improvements in mean scores on the self-evaluating spiral test and neurophysiological measures (p < 0.01 for all). Treatment effects lasted 8-12 weeks, with temporary numbness and pain reported, and no cumulative effects observed.
Ultrasound-guided IncoBoNT infiltrations show promise for oral treatment-resistant ET patients with minimal adverse effects. The anatomophysiological paradigm utilized proved beneficial for our patients, although tremor pattern variability remains a consideration.
Essential tremor patients often face limited options, as oral therapies often yield only partial efficacy, and invasive interventions, like Deep Brain Stimulation, may not always be viable. In this open-label study, 18 patients received ultrasound-guided IncobotulinumtoxinA injections, showing significant tremor improvement and enhanced quality of life, with minimal adverse events reported.This research was partially funded by Merz Therapeutics Iberia. The authors independently designed and conducted the study. No representatives from Merz Therapeutics Iberia participated in the collection, management, analysis, or interpretation of the data or in preparation, review, or approval of the manuscript
