Scientia, Dipòsit d’Informació Digital del Departament de Salut
Not a member yet
12576 research outputs found
Sort by
Longitudinal assessment of migraine burden in resistant and refractory migraine – Data from the prospective REFINE study
Get PDFChronic migraine; Disability; GepantsMigranya crònica; Discapacitat; GepantsMigraña crónica; Discapacidad; GepantesBackground: Some individuals with migraine fail to respond adequately to preventive treatments, bearing most of migraine burden. The European Headache Federation (EHF) classifies these individuals into resistant migraine (ResM) or refractory migraine (RefM) according to treatment failures, debilitating headache days, and disease duration. We investigated the evolution of these categories over six months in patients treated at tertiary headache centers and whether they accurately reflect disability and burden.
Methods: Participants from the multicenter, prospective REFINE study were classified into three categories of treatment responsiveness, namely RefM, ResM, and non-refractory non-resistant migraine (NRNRM). The primary objective was to determine the trajectories of category changes over six months. Secondary outcomes included changes in the 6-item Headache Impact Test (HIT-6), Headache-Attributed Lost Time (HALT), and Hospital Anxiety and Depression Scale (HADS-A and HADS-D) scores.
Results: Overall, 489 participants were included with a median age of 45 years (IQR = 36-53); 389 participants (79.7%) were female; 256 (52.4%) had NRNRM, 178 (36.4%) ResM, and 55 (11.2%) RefM. At follow-up, 200/256 (78.1%) NRNRM remained stable, while 56/256 (21.9%) progressed to ResM. Among those with ResM, 98/178 (55.1%) remained stable, 72/178 (40.5%) improved to NRNRM, and 8/178 (4.5%) worsened to RefM. Among participants with RefM, 37/55 (67.3%) remained stable, while 18/55 (32.7%) improved to NRNRM. Participants with RefM and ResM presented significantly higher scores at baseline than those with NRNRM. Over time, HIT-6, HALT, and HADS-A scores improved substantially in the overall cohort (p < 0.001, p < 0.001, and p = 0.006, respectively). Improvements were observed in participants with ResM across all scores and HIT-6 and HALT for NRNRM, but no improvement was noted in participants with RefM.
Conclusions: Over six months, ~ 40% of ResM and ~ 30% of RefM individuals improved to NRNRM, while ~ 20% of NRNRM developed treatment resistance after receiving care in tertiary headache centers. Participants with ResM had a better prognosis than those with RefM. While both ResM and RefM reflect high migraine disability burden, they might present relevant differences in their management and prognosis
Metabolic dysfunction-associated steatohepatitis reduces hepatic H2S-producing enzymes altering persulfidome composition
Get PDFSteatohepatitis; Metabolic dysfunction; PersulfidomeEsteatohepatitis; Disfunció metabòlica; PersulfidomaEsteatohepatitis; Disfunción metabólica; PersulfidomaMetabolic dysfunction–associated steatohepatitis (MASH) is a progressive disease driven by obesity-related hepatic inflammation and oxidative stress. Recently, cysteine persulfidation (PSSH), a protective post-translational modification by hydrogen sulfide (H2S), was established to play a role in redox regulation. Despite the role of the liver in H2S metabolism, the function of PSSH in MASH remains underexplored. We demonstrated that H2S-producing enzymes are downregulated in both human and mouse livers with steatosis and fibrosis, resulting in a decline in global PSSH levels. Dimedone-switch mass spectrometry in dietary mouse models of distinct obesity-associated liver disease stages revealed dysregulated PSSH on specific proteins. Surprisingly, increased hepatic PSSH levels of protein tyrosine phosphatases and redox regulators were found in advanced disease stages, suggesting a targeted adaptive response to oxidative stress. Overall, our findings demonstrated that impaired H2S production disrupts protective PSSH networks in MASH. However, selective PSSH preservation on redox-sensitive proteins may represent a compensatory mechanism, underscoring the therapeutic potential of persulfidation in restoring redox homeostasis during obesity-associated chronic liver disease.European Research Council (ERC) Consolidator grant METAPTPs GA817940 (ENG). FNRS-WELBIO grant (35112672), FNRS-Aspirant fellowship (40010598, 40024372) and ULB Foundation (ENG). European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme Grant Agreement No. 864921 (MRF). VIB grant (JM). Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A∗STAR) (WW). Biomedical Research Council (BMRC) Core Research Fund for use-inspired basic research and IAF-PP project H22J2a0043 (WW). Singapore National Medical Research Council (NMRC) project MOH-001401-00 (WW). FNRS-ASP scholarship and ENG is a Research Associate of the FNRS, Belgium (TKS)
Best practices in sample management and molecular profiling of cholangiocarcinoma: a practical guide
Get PDFCholangiocarcinoma; Molecular profiling; Tissue analysisColangiocarcinoma; Perfil molecular; Análisis de tejidosColangiocarcinoma; Perfil molecular; Anàlisi de teixitsIntroduction
Cholangiocarcinoma (CCA) is an uncommon yet aggressive malignancy often diagnosed at advanced stages. Its management is challenged by significant molecular heterogeneity and limited treatment options. Advances in next-generation sequencing (NGS) have identified actionable alterations, such as FGFR2 fusions, thereby facilitating a precision oncology approach for CCA management.
Areas Covered
This review consolidates current evidence and expert insights on molecular profiling in CCA. It examines the histopathological subtypes and addresses diagnostic challenges associated with their diagnosis. Critical pre-analytical factors, including biopsy techniques, tissue handling, and tumor heterogeneity, are discussed in relation to their impact on molecular testing. The review also evaluates DNA-based versus RNA-based NGS methodologies, highlighting their strengths and limitations in detecting complex genomic alterations. The role of liquid biopsy as a minimally invasive tool for dynamic tumor monitoring is also explored.
Expert Opinion
The routine integration of molecular profiling for CCA requires the best histopathological diagnosis and pre-analytical preparation practices. Diagnostic workflows should prioritize meticulous tissue handling to ensure robust molecular analyses to avoid tissue exhaustion and preserve the integrity of nucleic acids. Employing DNA plus RNA sequencing platforms, supported by molecular tumor boards, is recommended to enhance patient stratification and guide therapeutic decision-making in CCA.This paper was funded by Incyte Corporation
Deep Brain Stimulation in Children and Adolescents with ε-Sarcoglycan Myoclonus Dystonia Causes a Sustained Improvement in Motor Functionality and Quality of Life
Get PDFEstimulación cerebral profunda; Distonía mioclónica; Calidad de vidaDeep brain stimulation; Myoclonus dystonia; Quality of LifeEstimulació cerebral profunda; Distonia mioclònica; Qualitat de vidaBackground
Deep brain stimulation of the globus pallidus internus (DBS-GPi) has shown efficacy in adult patients with SGCE-related myoclonus dystonia. However, evidence regarding its impact in pediatric populations is limited.
Objectives
The aim was to evaluate motor and non-motor outcomes following DBS-GPi intervention in children and adolescents with SGCE-MD.
Methods
Ten patients (mean age 12.8 ± 3.4 years) underwent DBS-GPi. Blinded experts rated patients with the Unified Myoclonus, Burke-Fahn-Marsden, Writer's cramp and Gait Dystonia rating scales. Psychiatric and quality-of-life outcomes were evaluated using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria and Quality of Life in Neurological Disorders.
Results
Significant improvements were observed in myoclonus (68.1%), generalized dystonia (63.2%), and dystonia during writing (48.1%), walking (70.3%) and running (44.2%) after 3.8 ± 2.4 years of the surgery. Psychiatric symptoms remained stable, while quality-of-life assessments revealed reductions in anxiety, fatigue, and stigma (P < 0.05).
Conclusions
DBS-GPi in children with SGCE-myoclonus dystonia mitigates long-term disability, potentially enhancing academic, social, and professional prospects.The authors declare no potential conflict of interest with the present work. This work was supported by Instituto de Salud Carlos III (grant numbers PI21/00248, PI24/01083, and FORT23/00034) and the Boston Scientific Corporation (grant number PR[AMI]481/2021). A.S.V. was supported by La Caixa Postgraduate Abroad fellowship. A.C.G. was supported by the Agency for Management of University and Research Grants, AGAUR (2022 FI_B 00996). A.M.G. is granted a postdoctoral contract funded by Instituto de Salud Carlos III (ISCIII) through the project FORT23/00034
Expanding the SIAH1-Associated Phenotypic Spectrum: Insights From Loss-of-Function Variants
Get PDFExome sequencing; Loss‐of‐function; Phenotypic expansionSecuenciación del exoma; Pérdida de función; Expansión fenotípicaSeqüenciació de l'exoma; Pèrdua de funció; Expansió fenotípicaSIAH1 encodes for a RING-type E3 ubiquitin ligase involved in protein ubiquitination. More specifically, it positively regulates Wnt signaling through promoting the accumulation of β-catenin and mediates ubiquitination and degradation of Akt3 in neural development. Heterozygous de novo missense pathogenic variants in SIAH1 have been described in five unrelated individuals and are associated with developmental delay, hypotonia, and dysmorphic features. In this report, we present additional individuals from eight unrelated families and their clinical and genetic findings. We identified two missense and six predicted loss-of-function variants. Motor and speech delay and intellectual disabilities of varying severity were observed in all individuals. Neurodevelopmental issues, as well as infantile hypotonia and facial dysmorphism, were observed in the majority of individuals. Hearing loss, gastroesophageal reflux disease or other gastrointestinal issues, endocrinology abnormalities, and recurrent infections were observed in over 50% of individuals. This study expands the phenotypic spectrum of this syndrome and emphasizes the diverse impact of SIAH1 variation on multi-system clinical manifestations
Comparative Analysis of Ultrasonography and MicroCT Imaging for Organ Size Evaluation in Mice
Get PDFMice; Organ volume; UltrasoundRatolins; Volum d'òrgans; EcografiaRatones; Volumen de órganos; EcografíaIn this work, the authors compared microCT and in vivo ultrasonography in terms of accuracy and efficacy for measuring the volume of various organs in mice. Two quantification protocols were applied: ellipsoidal volume measuring maximum diameters in all three axes in both imaging systems and manual delineation of organ borders in microCT studies. The results were compared with ex vivo volumes. In general, both imaging techniques and quantification protocols are accurate, but ultrasound is faster in both acquisition and analysis. The only accurate method for heart volume measurement is manual segmentation on microCT. For the ovary, none of the techniques and protocols had a positive correlation with ex vivo volume. The three-diameter method can be used for ellipsoid organs because of its rapidity, but for more irregular structures, manual segmentation is recommended, although it is time-consuming
Secondary resistance to sonidegib is rare in locally advanced basal cell carcinoma
Get PDFSecondary resistance; Locally advanced basal cell carcinomaResistencia secundaria; Carcinoma basocelular localmente avanzadoResistència secundària; Carcinoma basocel·lular localment avançatThe BOLT study was sponsored and funded by Novartis; this analysis was funded by Sun Pharma. Medical writing and editorial support were funded by Sun Pharma Europe B.V
Robotic ventral rectopexy videos on youtube: reliability of quality and educational value assessment among raters with different degrees of surgical experience
Get PDFRobotic rectopexy; Surgical videos; Ventral rectopexyRectopèxia robòtica; Vídeos quirúrgics; Rectopèxia ventralRectopexia robótica; Vídeos quirúrgicos; Rectopexia ventralPurpose
Robotic ventral rectopexy (RVR) has gained acceptance as a minimally invasive approach for treating rectal prolapse and rectocele. Although numerous surgical videos have been published, their educational quality remains underexplored. This study aimed to evaluate the overall quality, adherence to reporting guidelines, and educational value of the most-viewed RVR videos on YouTube, as rated by surgical trainees, fellows, and senior surgeons.
Methods
The 25 most-viewed YouTube videos on RVR were selected and assessed for adherence to LAP-VEGaS and consensus reporting guidelines, overall quality, and educational value. Surgeons’ performance was evaluated using the Global Evaluative Assessment of Robotic Skills (GEARS) scale. A Bayesian ordinal regression model analyzed factors influencing video quality and utility ratings.
Results
Video quality and educational value varied significantly among viewer groups. Only 40% of videos underwent peer review before publication. Adherence to reporting guidelines was low (median conformity rate: 13.5%-16.7%). Inter-rater reliability differed across GEARS domains, with senior surgeons rating video quality and utility more critically than trainees and fellows. Videos with more likes and shorter online duration were more likely to be rated as high-quality.
Conclusions
Online surgical videos on RVR offer easily accessible but potentially unreliable educational resources and exhibit significant variability in quality and guideline adherence. Structured, peer-reviewed video-based educational programs and standardized reporting practices are crucial for improving the educational impact of online surgical videos
Emergency Department Reconsultations After a Secondary Prevention Bundle for Medication-Related Problems: A Retrospective Cohort Study
Get PDFDrug-related problems; Emergency department; Older adults; Readmission; Secondary preventionProblemas relacionados con medicamentos; Servicio de urgencias; Reingreso; Prevención secundariaProblemes relacionats amb medicaments; Servei d'urgències; Reingrés; Prevenció secundàriaBackground/Objective: Drug-related problems (DRPs) are a common, potentially avoidable cause of emergency department (ED) use. In December 2022, our hospital integrated a pharmacist-led intervention into routine ED practice. This intervention comprised medication optimization, adherence counseling, and coordinated hand-off to primary care. We quantified 30- and 90-day reconsultations after discharge and explored factors associated with DRP-related revisits. Methods: A retrospective cohort of adults (≥18 years) who attended a tertiary ED (Barcelona, Spain). We included index DRP visits from 1 December 2022 to 30 June 2024. All received the bundle. Demographic, clinical, and pharmacotherapeutic data were extracted from the Catalan Shared Health Record; an independent committee classified revisits as a DRP or non-DRP. Predictors of 30-day DRP revisits were assessed with multivariable logistic regression. Results: Among 1247 patients (mean age 78.6 ± 16.2 years; 59.2% women; and median nine drugs), 120 (9.6%) reconsulted the ED within 30 days, and 194 (15.5%) within 90 days for any cause. DRP-specific rates were 30.8% (37/120) at 30 days and 26.3% (51/194) at 90 days; 81% and 80% of these revisits, respectively, involved a recurrence of the same DRP. The most frequent index DRPs were constipation (14.2%), gastrointestinal bleeding (9.2%), hypertension (8.3%), seizures (8.3%) and hyponatraemia (6.7%). An age ≥ 80 years independently predicted fewer 30-day DRP revisits (OR 0.32; 95% CI 0.13-0.79); hypertension and cognitive impairment were not significant after adjustment. Conclusions: In this single-arm implementation cohort, overall, 30-day ED reconsultations were 9.6% and about one-third were DRP-related, predominantly recurrences, and chiefly gastrointestinal bleeding and seizures. These descriptive findings should be interpreted cautiously given potential survivorship bias and residual confounding; the apparently lower risk among patients aged ≥ 80 years is hypothesis-generating and may reflect geriatric care pathways and caregiver engagement. Targeted post-discharge monitoring for high-recurrence DRPs may help reduce avoidable ED use, and future evaluations should test this in quasi-experimental or randomized designs
Cabozantinib plus Atezolizumab in Advanced, Progressive Endocrine Malignancies: A Multicohort, Basket, Phase II Trial (CABATEN/GETNE-T1914)
Get PDFCabozantinib; Atezolizumab; Advanced progressive endocrine malignanciesCabozantinib; Atezolizumab; Neoplasias endocrinas avanzadas y progresivasCabozantinib; Atezolizumab; Neoplàsies endocrines avançades i progressivesPurpose:
Multikinase inhibitors have shown efficacy in endocrine neoplasms, and synergism with immune checkpoint inhibitors has been noted in other tumors.
Patients and Methods:
This is a prospective, multicenter, open-label, Simon two-stage optimal design, phase II study including patients with advanced and refractory endocrine and neuroendocrine neoplasms in six cohorts: lung well-differentiated neuroendocrine tumors, anaplastic thyroid cancer (ATC), adrenocortical carcinoma (ACC), pheochromocytoma/paraganglioma (PPGL), well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NET), and grade 3 extrapulmonary neuroendocrine neoplasms. Patients received atezolizumab 1,200 mg intravenously every 3 weeks plus cabozantinib 40 mg/day orally until disease progression or unacceptable toxicity. The primary objective was the overall response rate (ORR) by RECIST 1.1.
Results:
From October 2020 to December 2022, 93 patients were included. The ORR was 14.3% [95% confidence interval (CI), 1.8–42.8] in ATC (N = 14); 8.3% (95% CI, 1.0–27.0) in ACC (N = 24); 15.4% (95% CI, 1.9–45.5) in PPGL (N = 13), and 16.7% (95% CI, 4.7–37.4) in GEP-NET (N = 24). Lung well-differentiated neuroendocrine tumors and grade 3 extrapulmonary neuroendocrine neoplasms had no responses. The duration of response was 20.4 months in ATC, 13.1 months in ACC, 12.2 months in PPGL, and 15.8 months in GEP-NET. Survival rates at 12 months in ATC and ACC were 47.6% and 47.6%, respectively. No unexpected toxicity was observed.
Conclusions:
Cabozantinib and atezolizumab were safely administered and showed promising ORR, and preliminary long-term survival rates were observed in aggressive and pretreated ACC and ATC, which warrants further investigation.This work was supported by the Grupo Español de Tumores Neuroendocrinos y Endocrinos. Roche provided atezolizumab, whereas Ipsen supplied cabozantinib and awarded a grant to Grupo Español de Tumores Neuroendocrinos y Endocrinos to cover the costs of the study. The funders have no role in the design, conduct, or analysis of the study. The authors thank all patients and families, investigators, and study staff involved in the CABATEN trial; special thanks to the MFAR Clinical Research team for their support in regulatory, monitoring, and quality assurance activities; Pau Doñate, Ph.D., and Fanny Rubio, Ph.D., for their assistance with manuscript and language editing; and Oriol Prat M.S. for his statistical support