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Global frequency, diagnosis, and treatment of hereditary angioedema with normal C1 inhibitor
Full text linkHereditary angioedema; Diagnostics; TreatmentAngioedema hereditario; Diagnóstico; TratamientoAngioedema hereditari; Diagnòstic; TractamentBackground: Hereditary angioedema (HAE) is a rare genetic disease, most frequently associated with deficiency or dysfunction in the C1 inhibitor protein. HAE with normal C1 inhibitor (HAE-nC1INH) lacks standardized diagnostic tests, limiting precise prevalence estimates and development of specific treatment guidelines.
Objective: This study sought to describe the global frequency, diagnostic pathway, and current treatment patterns of HAE-nC1INH.
Methods: Board-certified HAE-treating physicians from accredited Angioedema Centers of Reference and Excellence (ACAREs) were invited to complete a 27-item online survey between December 2022 and April 2023.
Results: Thirty physicians from 30 ACAREs across 15 countries reported a mean of 71 (range, 11-148) patients with HAE assessed/treated within the previous 12 months. On average, physicians estimated 24% (range, 2-44%) of patients with HAE were diagnosed with HAE-nC1INH, most of whom were adults (88%). To diagnose HAE-nC1INH, physicians most commonly assessed family history and plasma C4 levels (90% each), and C1 function and quantitative levels (87% each). On-demand and prophylactic treatment patterns varied widely across countries, with an average (range) of 56% (33-100%) of patients receiving on-demand treatment only, and 37% (0-67%) receiving both on-demand and prophylactic treatment. Physicians identified the greatest unmet needs in HAE-nC1INH management as treatment specifically indicated for this patient population and availability of an oral treatment.
Conclusion: HAE-nC1INH may be more prevalent than previously reported. Importantly, our findings revealed varying diagnostic and treatment approaches. Validated, accessible diagnostic biomarkers and clinical outcomes derived from rigorous clinical trials assessing mechanistically based treatments would advance understanding and management of HAE-nC1INH
Postoperative Outcomes Are Comparable Between Arthroscopic Subscapularis Repairs Performed With Either All-Suture Anchors or Hard-Body Anchors
Full text linkResultats postoperatoris; Reparacions artroscòpiques; Ancoratges de sutura completaResultados posoperatorios; Reparaciones artroscópicas; Anclajes de sutura completaPostoperative outcomes; Arthroscopic repairs; All-suture anchorsPurpose
To compare clinical outcomes and tendon healing rates of patients undergoing arthroscopic rotator cuff repairs involving the subscapularis (SSC) tendon (isolated or combined) with all-suture anchors (ASAs) versus hard-body anchors (HBAs) and to compare SSC healing rates between these 2 anchors.
Methods
A retrospective comparative study was performed on patients who underwent arthroscopic rotator cuff repair of the SSC with either ASAs or HBAs and had a minimum 2-year follow-up. Range of motion and patient-reported outcomes were collected pre- and postoperatively, including a visual analog scale for pain, American Shoulder and Elbow Surgeons score, and Subjective Shoulder Value. Postoperative strength was measured, including Constant strength and belly press test. SSC healing was evaluated on ultrasounds at the final follow-up.
Results
Eighty-four patients met the study criteria. Twenty-eight underwent SSC repair with ASAs and 56 with HBAs. The mean follow-up for the ASA group and HBA group was 44 ± 22.7 months and 48.4 ± 28.3, respectively (P = .743). Baseline characteristics were comparable between groups (P > .05). Overall, patient-reported outcomes and range of motion showed significant improvements from baseline to the final follow-up in all groups (P < .001). Postoperatively, patients in the ASA group had greater improvement in forward flexion compared to the HBA group: 31° (95% confidence interval, 20°-42°) versus 14° (95% confidence interval, 5°-8°), respectively (P = .002). Postoperative Constant strength was higher in the ASA group compared to the HBA group: 17.5 ± 7.5 versus 13.5 ± 5.6, respectively (P = .04). No statistically significant difference in SSC retear rates was observed between groups: none in the ASA group and 3 (10.7%) in the HBA group (P = .27).
Conclusions
Arthroscopic SSC repair leads to significant functional improvement, with both ASAs and HBAs demonstrating similar low failure rates.
Level of Evidence
Level III, retrospective cohort study
Educació en neurociència del dolor: material de suport en l’abordatge multimodal del dolor crònic [manual]
No full textNeurociència del dolor; Dolor crònic; DesmedicalitzacióNeurociencia del dolor; Dolor crónico; DesmedicalizaciónNeuroscience of pain; Chronic pain; DemedicalizationEl Grup de treball sobre SSC del PADEICS (Programes Assistencials d’Expertesa de l’ICS) proposa un material educatiu en Neurociència del Dolor per utilitzar individualment a la consulta d’Atenció Primària i Hospitalària.El Grupo de trabajo sobre SSC del PADEICS (Programas Asistenciales de Expertosa del ICS) propone un material educativo en Neurociencia del Dolor para utilizar individualmente en la consulta de Atención Primaria y Hospitalaria.The Working Group on SSC of the PADEICS (ICS Expert Assistance Programs) proposes an educational material on Neuroscience of Pain to be used individually in Primary Care and Hospital consultations
Population pharmacokinetics and exposure-response relationships of dostarlimab in primary advanced or recurrent endometrial cancer in part 1 of RUBY
Full text linkClinical pharmacology; Oncology; PharmacokineticsFarmacología clínica; Oncología; FarmacocinéticaFarmacologia clínica; Oncologia; FarmacocinèticaAims
Dostarlimab-gxly is a humanized monoclonal antibody of the IgG4 isotype that binds to the programmed cell death protein-1 (PD-1) receptor and blocks its ligands. RUBY (NCT03981796) is a two-part multicentre study in patients with recurrent or primary advanced endometrial cancer. The overall aims were to characterise the population pharmacokinetics (PopPK) from Part 1 of this study, identify relevant covariates of interest, and assess exposure–efficacy/safety (ER) relationships.
Methods
A PopPK model developed using GARNET (NCT02715284) study data for dostarlimab monotherapy was externally validated with RUBY Part 1 study data. Subsequently, the model was updated with data across the two studies. Exposure–safety analyses for adverse events related to dostarlimab alone or in combination with standard of care (SOC) were modelled using logistic regression. Exposure–efficacy analysis included Cox proportional hazards analysis of the primary efficacy endpoint of progression-free survival (PFS).
Results
For the model update, 7957 pharmacokinetics observations from 868 patients pooled from both RUBY and GARNET studies were available. The model was consistent with the previous model. Dostarlimab clearance was estimated to be 7.79% lower when dostarlimab was given as SOC combination therapy. However, no significant covariates were clinically relevant. Hepatic or renal impairment did not affect pharmacokinetics. Among the safety endpoints, only rash showed a small yet statistically significant effect (P < .05) in all subjects; however, this was not not deemed clinically relevant. There were no other clinically significant exposure–safety or exposure–PFS relationships.
Conclusions
The addition of chemotherapy to dostarlimab had limited effect on dostarlimab PopPK, with no clinically significant covariates or clinically relevant exposure–safety or exposure–PFS relationships.These studies (NCT02715284 and NCT03981796) were funded by GSK
Real-world radiology data for artificial intelligence-driven cancer support systems and biomarker development
Full text linkRadiology; Artificial intelligence; OncologyRadiología; Inteligencia artificial; OncologíaRadiologia; Intel·ligència artificial; OncologiaThe integration of artificial intelligence (AI) and real-world data (RWD) opens up a new paradigm for exploiting radiology data to develop advanced diagnostic and therapeutic support systems. This review explores the advantages and challenges of utilizing vast digital image datasets from routine clinical practice and computational AI capabilities to enhance cancer patient care. Particularly, the application of AI to radiology data has shown promise in developing tools that automate clinical processes, such as tumor detection, while also identifying novel biomarkers in cancer for potential treatment support. Deep learning models, crucial for this transformation, require substantial data, making RWD a valuable resource for accelerating assay development. RWD offer diverse, extensive data reflecting real-world clinical practices, complementing clinical trial data and providing a broader understanding of patient populations and treatment responses. However, challenges such as data access, variability in quality, and processing complexities must be addressed. Standardizing data processing protocols and feature extraction methods is essential to ensure reproducibility and clinical applicability. Moreover, building trust among clinicians, patients, and regulatory bodies is crucial for successful implementation. This review highlights the potential of AI to analyze RWD imaging data and radiology reports, extracting relevant information and enhancing biomarker discovery. To facilitate practical use, we offer tools to address the main challenges associated with utilizing real-world imaging data, such as key aspects of image access and data processing
Genetic immune escape in cancer: timing and implications for treatment
Full text linkImmunotherapy resistance; Tumor evolution; Tumor microenvironmentResistencia a la inmunoterapia; Evolución del tumor; Microambiente tumoralResistència a la immunoteràpia; Evolució del tumor; Microambient tumoralGenetic immune escape (GIE) alterations pose a significant challenge in cancer by enabling tumors to evade immune detection. These alterations, which can vary significantly across cancer types, may often arise early in clonal evolution and contribute to malignant transformation. As tumors evolve, GIE alterations are positively selected, allowing immune-resistant clones to proliferate. In addition to genetic changes, the tumor microenvironment (TME) and non-genetic factors such as inflammation, smoking, and environmental exposures play crucial roles in promoting immune evasion. Understanding the timing and mechanisms of GIE, alongside microenvironmental influences, is crucial for improving early detection and developing more effective therapeutic interventions. This review highlights the implications of GIE in cancer development and immunotherapy resistance, and emphasizes the need for integrative approaches
Psychometric properties of the nursing critical thinking in clinical practice questionnaire in clinical nurse educators
Full text linkCritical thinking; Nurse educator; Psychometric propertiesPensament crític; Infermera educadora; Propietats psicomètriquesPensamiento crítico; Enfermera educadora; Propiedades psicométricasThe Nursing Critical Thinking in Clinical Practice Questionnaire is an instrument designed to measure the critical thinking capacity of nurses working in clinical areas. However, there is little existing research on the potential applications of this instrument specifically in clinical nurse educators involved in the training of university nursing students. Therefore, we used a descriptive cross-sectional design to examine the psychometric properties of the questionnaire in clinical nurse educators. We evaluated the construct and convergent validity, assessed the reliability of the questionnaire, and performed a confirmatory factor analysis. A total of 639 clinical nurse educators took part in this study. Results of the Confirmatory Factor Analysis showed a good fit to the model (CFI 0.97, NFI: 0.95). The total Cronbach’s alpha was 0.97. The four factors had an internal consistency > 0.7. The interclass correlation coefficient values were 0.78 [95% CI 0.75–0.81] for the whole instrument and 0.70–0.75 for the various dimensions, and all were statistically significant at p < 0.05. These findings suggests that the Nurse Critical Thinking in Practice Questionnaire is a useful tool for measuring critical thinking levels in clinical nurse educators. This enhances the knowledge of all agents involved in the learning process, making it easier to implement in clinical practice.
Clinical Trial Registration: This study was prospectively registered at the two Institutional review boards.This study was financed by the University of Barcelona (Universitat de Barcelona), grant number PREI-20-001-A. Barcelona, Spain. And also funded by the Departament de Recerca i Universitats de la Generalitat de Catalunya - AGAUR (grant number 2021 SGR 00929)
Prognostic Models From Transcriptomic Signatures of the Tumor Microenvironment and Cell Cycle in Stage III Colon Cancer From PETACC-8 and IDEA-France Trials
Full text linkPrognostic models; Tumor microenvironment; Colon cancerModelos pronósticos; Microambiente tumoral; Cáncer de colonModels pronòstics; Microambient tumoral; Càncer de còlonPurpose
The objective of this work was to establish prognostic models in stage III colon cancer (CC) on the basis of transcriptomic signatures of the tumor microenvironment (TME) and cell cycle from the PETACC-8 (training set) and IDEA-France (validation set) trials.
Patients and Methods
3'RNA sequencing was performed in 1,733 patients from the PETACC-8 trial and 1,248 patients from the IDEA-France trial. Four transcriptomic signatures were analyzed: T-cell and macrophage M2 signatures, the expression of CXCL13, and a score on the basis of the Oncotype DX CC Recurrence Score using the same formula from the stromal score and the cell cycle score. The Immune Proliferative Stromal (IPS) score was defined as the number of dichotomized signatures that fall under the category of a dismal prognosis (from 0 to 4). Time to recurrence (TTR) was defined as the time from the date of random assignment to local and/or metastatic relapse and/or death because of CC, whichever occurs first.
Results
High Oncotype-like and M2 scores and low CXCL13 expression and T-cell score were associated with a shorter TTR. A multivariable model including these signatures and all known prognostic factors applied to the IDEA-France cohort by obtaining a value of this model for each patient showed TTR significantly different depending on the quartile of this value and a 3-year rate of patients without recurrence ranging from 56% for the lowest quartile to 89% for the highest quartile (P < .0001). The IPS score was significantly associated with TTR in multivariable analysis.
Conclusion
Using transcriptomic data of patients with stage III CC from two large-scale adjuvant trials, a prognostic model on the basis of signatures of the TME and the cell cycle provides important information in addition to known prognostic factors for patient stratification on risk of recurrence
How to combine multiple tools for the genetic diagnosis work-up of pediatric B-cell acute lymphoblastic leukemia
Full text linkAcute lymphoblastic leukemia; Genetic diagnosis; Multiple-technique approachLeucèmia limfoblàstica aguda; Diagnòstic genètic; Enfocament multitècnicLeucemia linfoblástica aguda; Diagnóstico genético; Enfocament multitécnicoThis study investigated the importance of comprehensive genetic diagnosis in pediatric B-cell acute lymphoblastic leukemia (B-ALL). We analyzed 175 B-ALL employing karyotyping, FISH, MLPA, targeted next-generation sequencing (t-NGS), and Optical Genome Mapping (OGM). This approach achieved an 83% classification rate, identifying 17 distinct genetic subtypes. Specifically, within B-other subtype, seven different subgroups were identified (ZNF384, IGH, DUX4, NUTM1 rearrangements, PAX5 alterations, PAX5 P80R, and IKZF1 N159Y). Secondary genetic alterations were observed, with copy number alterations (CNA) present in 60% of cases and mutations detected in 70.6%. While these alterations exhibited specific associations with certain genetic subtypes, CNAs did not appear to significantly impact the prognosis within these genetic groups. HeH, ETV6::RUNX1, ZNF384-r, and PAX5 P80R exhibited excellent outcomes, contrasting with the poor prognoses observed in KMT2A-r, hypodiploidy, and CRLF2-r (5-year overall OS were 50%, 50%, and 52%, respectively). These findings underscore the value of integrated genetic diagnostics for accurate subtyping, risk stratification, and guiding personalized treatment in pediatric B-ALL. Therefore, optimizing diagnostic workflows for routine clinical practice is crucial. Our study confirms the utility of conventional techniques (karyotyping and FISH), combined with t-NGS and OGM, for comprehensive genetic diagnosis.This work was supported by the FERO Foundation under Grant 3281
Real-world evidence of effectiveness and safety of pasireotide in the treatment of acromegaly: a systematic review and meta-analysis
Full text linkAcromegaly; Effectiveness; PasireotideAcromegalia; Efectividad; PasireotidaAcromegàlia; Efectivitat; PasireòtidaPasireotide long-acting release (PAS-LAR) is a second-generation somatostatin receptor ligand (SRL) approved for acromegaly treatment. This meta-analysis aimed to evaluate the real-world effectiveness and safety of PAS-LAR in patients with acromegaly resistant to first-generation somatostatin receptor ligands (fgSRL). A systematic literature search was conducted in PubMed and Web of Science for real-world studies on PAS-LAR in acromegaly published between 2014 and 2023. Random-effects meta-analyses were performed on biochemical control rates, tumor shrinkage, and metabolic parameters. Twelve studies comprising 409 patients were included. The pooled rate of insulin-like growth factor 1 (IGF-1) control was 57.9% [95% CI: 48.4–66.8] and the percentage of patients with tumor shrinkage was 33.3% [95%CI: 19.7–50.4]. Significant reductions were observed in growth hormone standardized mean difference (SMD) 0.6 ng/mL [95% CI: 0.3 to 1.0] and IGF-1 levels SMD 0.9 ULN [95% CI: 0.4 to 1.4]. However, as expected, a worsening in glucose metabolism was noted as an increase in fasting glucose SMD − 0.8 mg/dL [95% CI: -1.0 to -0.5, p < 0.01], glycated hemoglobin SMD − 0.5% [95% CI: -0.7 to -0.2]. and type 2 diabetes mellitus prevalence SMD − 11.5% (95% CI: -17.5 to -5.5). PAS-LAR demonstrated higher effectiveness in real-world settings, with over 60% of patients achieving IGF-1 control compared to the around 30% efficacy observed in clinical trials. These findings suggest that PAS-LAR is an effective option for acromegaly patients resistant to fgSRL, but careful monitoring of glucose levels is essential. The high heterogeneity observed across studies emphasizes the need for identifying PAS-LAR response biomarkers to set-up individualized treatment approaches for optimizing patient outcomes