Search Results (11)

Background/Objectives: This PETHEMA PCR-LMA study aimed to evaluate whether mutations detected by NGS (VAF cut-off of ≥5%) correlate with NPM1, FLT3-ITD, FLT3-TKD, IDH1, and IDH2 mutations detected using conventional PCR (analytical sensitivity 3%) in a nationwide network of seven reference laboratories. Methods: Between 2019 and 2021, 1685 adult AML patients with at least one centralized sample (NGS or PCR) at primary diagnosis or relapse/refractory episode were included. Results: During this period, 1288 paired NGS/PCR samples (1094 at diagnosis, 103 at relapse and 88 at refractoriness) were analyzed. Considering PCR the gold-standard, for NPM1 NGS sensitivity was 98.5% and specificity 98.9%, for FLT3-ITD 73.8% and 99.6%, for FLT3-TKD 84.5% and 99.3%, for IDH1 98.7% and 98.7%, and for IDH2 99.1% and 97.7%, respectively. Overall concordance rate of positive results between NGS (and PCR was 95% (262/276) for NPM1, 72% (149/206) for FLT3-ITD, 74% (49/66) for FLT3-TKD, 87% (77/89) for IDH1 and 84% (107/127) for IDH2. Overall, median days from sample reception until report were 7 for PCR and 28 for NGS. Conclusions: This study shows high concordance between NPM1 and IDH results using PCR and NGS. However, sensible important discrepancies are observed for FLT3 mutations. In our context, rapid screening for these druggable mutations should be performed by conventional PCR. Full article

Background: Patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who are ineligible for high-dose chemotherapy have limited treatment options and poor life expectancy. The purpose of this study is to identify a serum metabolomic profile that may be predictive of outcome in patients with R/R-DLBCL. Methods: This study included 69 R/R DLBCL patients from the R2-GDP-GOTEL trial (EudraCT 2014-001620-299). Serum samples were collected at baseline, and the mean length of follow-up was 41 months. Serum metabolites were analyzed by nuclear magnetic resonance (NMR). Metabolites were correlated with treatment response, progression-free survival (PFS), and overall survival (OS). Results: Serum levels of 3-hydroxybutyrate (3OHB) and acetone were significantly (p < 0.001) associated with PFS (3OHB: hazard ratio [HR] 7.7, 95% confidence interval [CI] 2.5–24.1; acetone: HR 9.32, 95% CI 2.75–31.6) and OS (3OHB: HR 9.32, 95% CI 2.75–31.6; acetone: HR 1.92, 95% CI 1.36–2.69). Serum values of 141 µM for 3OHB and 40 µM for acetone were the optimal cutoffs associated with the survival outcomes. Elevated 3OHB levels (>141 μM) were specific to the ABC subtype of DLBCL, while acetone levels were elevated in both types of DLCBL but more pronounced in ABC cases. In a multivariate survival analysis, including the International Prognostic Index (IPI) score and refractoriness status (R/R), 3OHB and acetone remained significant. To aid oncologists employing the R2-GDP regime, we constructed PFS and OS nomograms for R/R-DLBCL risk stratification, incorporating 3OHB levels or acetone levels, IPI score, and refractoriness status. The nomogram with 3OHB and refractoriness status showed a time-dependent AUC of 0.86 for 6-month PFS and 0.84 for 12-month OS. These nomograms provide a comprehensive tool for individualized risk assessment and treatment optimization. Conclusions: The ketone bodies 3OHB and acetone are potential prognostic biomarkers of poor outcome in R/R DLBCL patients treated with the R2-GDP regimen, independently of IPI score and chemorefractoriness status. Full article

The primary objective of this study was to conduct a cost–utility analysis of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in real-world, comparing their use with standard care for managing cardiovascular disease. A multicenter prospective study was conducted across 12 Spanish hospitals from May 2020 to April 2022, involving 158 patients with hypercholesterolemia or atherosclerotic cardiovascular disease. This study assessed health-related quality of life (QoL) using the EQ-5D-3L questionnaire. The cost–utility analysis evaluated the economic impact of PCSK9 inhibitors when used with standard care compared to standard care alone, calculating the incremental cost–effectiveness ratio (ICER). This study included 158 patients with an average age of 61 years, male (66.5%). For patients initiating PCSK9 inhibitors, the treatment cost was EUR 13,633.39, while standard therapy cost EUR 3638.25 over two years. QoL for PCSK9 inhibitors stood at 1.6489 over two years, compared to 1.4548 for standard therapy. The results revealed favorable cost–utility outcomes, with an ICER of EUR 51,427.72. Significant improvements were observed in the domains of mobility, self-care, daily activities, pain/discomfort, and anxiety/depression (p < 0.001). This study presents the first real-world cost–utility analysis of PCSK9 inhibitors, supporting their economic rationale and highlighting their benefits in clinical practice. Healthcare decision-makers can use these results to inform their decisions and reimbursement policies concerning PCSK9 inhibitors. Trial Registration clinicaltrials.gov Identifier: NCT04319081. Full article

Background: The pathogenicity of the different genetic variants causing hypertrophic cardiomyopathy (HCM) and the genotype/phenotype correlations are difficult to assess in clinical practice, as most mutations are unique or identified in non-informative families. Pathogenic variants in the sarcomeric gene MYBPC3 inherited with an autosomal dominant pattern, whereas incomplete and age-dependent penetrance are the most common causes of HCM. Methods: We describe the clinical characteristics of a new truncating MYBPC3 variant, p.Val931Glyfs*120, in 75 subjects from 18 different families from northern Spain with the p.Val931Glyfs*120 variant. Results: Our cohort allows us to estimate the penetrance and prognosis of this variant. The penetrance of the disease increases with age, whereas 50% of males in our sample developed HCM by the age of 36 years old, and 50% of women developed the disease by the time they reached 48 years of age (p = 0.104). Men have more documented arrhythmias with potential risk of sudden death (p = 0.018), requiring implantation of cardioverter defibrillators (p = 0.024). Semi-professional/competitive sport among males is related to earlier onset of HCM (p = 0.004). Conclusions: The p.Val931Glyfs*120 truncating variant in MYBPC3 is associated with a moderate phenotype of HCM, with a high penetrance, onset in middle age, and a worse outcome in males due to higher risk of sudden death due to arrhythmias. Full article

Drones have become a crucial research tool across marine environments over the past decade, being specifically useful in marine mammal research. Fin whales (Balaenoptera physalus) have been monitored feeding along the Catalan coast, Spain (NW Mediterranean), since 2014. To overcome issues such as the distance between a whale and a research vessel or the lack of distinctive dorsal fin features, an aerial identification technique was developed. It uses the fin whales’ characteristic central chevron pattern (CCP) and blaze, which are clearly visible from an overhead position. A total of 237 individual whales were identified between 2015–2022 in this study area, of which there were 35 interannual recaptures. While the dorsal fin may undergo modifications over time, the CCP and blaze patterns did not naturally alter over the years, with one whale displaying the same characteristics 8 years apart between the first and the most recent sightings. As such, this coloration pattern provides a reliable identification feature to be used for the interannual identification and population monitoring of fin whales using drones. This novel technique aims to improve and unify this species cataloguing overseas by using the CCP and blaze obtained from UAV (unmanned aerial vehicle) zenithal videos as a robust identification tool. Full article

Inclusive education is fundamental, consisting of enabling all students, irrespective of their characteristics, to receive appropriate education and actively participate in school life. Teachers play an important role in this regard; thus, this study aims to analyze teachers’ perceptions regarding their preparation for inclusion by assessing possible differences depending on the educational stage (early childhood, primary, or secondary education). A total of 1098 Spanish teachers, from Extremadura, responded to three dichotomic answers about their inclusive education preparation perception and the Evaluation of Teachers’ Inclusion Readiness (CEFI-R) questionnaire, a 19-item tool composed of four dimensions: (1) conception of diversity, (2) methodology, (3) support, and (4) community participation. Pearson’s chi-square test was used to assess differences between the dichotomous questions and educational stage; Kruskal–Wallis was used to determine whether the educational stage conditioned the CEFI-R dimensions responses, and the Spearman rho was used to test the association between age groups and the CEFI-R dimensions. Statistical differences were found between secondary education and preschool education and primary education teachers in the dimensions (1) conception of diversity, (2) methodology, and (3) support. Significant differences in dimension (4) community participation between preschool education teachers and secondary and primary education teachers were found. Full article

Introduction. Inclusive education is one of the main objectives of the educational system toward achieving equal opportunities among students. To this end, teacher training plays an important role in the different educational stages. Objectives. To analyze the perceived readiness of teachers for inclusive education and to see the differences in primary and secondary education. Methods: A total of 961 active teachers from public schools, 53.3% Primary and 46.7% Secondary Education, were analyzed by means of a questionnaire on Teachers’ perceptions about their preparation for inclusive education and the CEFI-R instrument. Results. There are statistically significant differences between the two stages in the first questionnaire (question 1: p = 0.03; question 2: p < 0.01 and question 3: p < 0.01) and also, in 3 of the four CEFI-R dimensions, with the primary score being higher. Conclusions: This study shows that there is a large percentage of teachers who believe that their initial training is insufficient to deal with student diversity. In addition, most of them state that continuous training has helped them to improve inclusive education and that they would be willing to attend training courses on inclusion, although in secondary school, the predisposition is lower than in high school. On the other hand, teachers of both educational stages show a mostly favorable attitude according to the CEFI-R, being higher in primary than in secondary school. In this sense, the public administration has work to do. Full article

Inclusive education (IE) refers to the education of all learners, with or without disabilities, irrespective of their status or origin, who share the same learning spaces. IE is a multidimensional approach based on rights and quality of life paradigms. As teachers are agents of change, they must have the knowledge and competencies to meet this challenge. This study aimed to find potential associations between teachers’ preparation and their age and years of teaching experience. A cross-sectional study with a sample of 1275 teachers working in early childhood, primary and secondary education was performed. They answered three dichotomic questions about their initial and ongoing preparation and The Evaluation of Teacher Preparation for Inclusion (CEFI-R) Questionnaire. The dichotomic questions showed that 26.4% of respondents felt qualified to face the challenges of their students’ diversity. There were significant inverse associations between the CEFI-R Dimension 1 (diversity conception), Dimension 3 (supports), and Dimension 4 (community participation) and the teachers’ age and years of teaching experience. This means that the higher the age or the years of experience, the teachers’ perceived preparation for inclusion is worse, which should encourage us to take measures to improve teachers’ competencies and preparedness. Full article

Inclusive education is a right for every student, being one of the current challenges with which the education system is struggling. The teacher’s role in this process is essential in building an inclusive and transformative school. This study aims to measure Spanish secondary school teachers’ perceptions of their preparation to address inclusive education, exploring whether there are differences concerning their gender. A total of 420 Spanish secondary school teachers responded to three dichotomous questions about their initial and ongoing preparation using the Evaluation of Teacher Education for Inclusion Questionnaire (CEFI-R). The results suggest that there are no significant differences between men and women regarding their perceived readiness to deal with diversity. However, women seem to be more confident in their competence, as they show less need for preparation in addressing the diversity of needs in their students with disabilities, and in promoting inclusive education. Full article

Annexin-A1 (AnxA1) and its N-terminal derived peptide Ac2-26 regulate the inflammatory response in several experimental models of disorders. This study evaluated the effect of endogenous AnxA1 and its N-terminal peptide Acetyl 2-26 (Ac2-26) on allergic asthma triggered by house dust mite (HDM) extract in mice. ANXA1^−/− and wildtype (WT) mice were exposed to intranasal instillation of HDM every other day for 3 weeks, with analyses performed 24 h following the last exposure. Intranasal administration of peptide Ac2-26 was performed 1 h before HDM, beginning 1 week after the initial antigen application. ANXA1^−/− mice stimulated with HDM showed marked exacerbations of airway hyperreactivity (AHR), eosinophil accumulation, subepithelial fibrosis, and mucus hypersecretion, all parameters correlating with overexpression of cytokines (IL-4, IL-13, TNF-α, and TGF-β) and chemokines (CCL11/eotaxin-1 and CCL2/MCP-1). Intranasal treatment with peptide Ac2-26 decreased eosinophil infiltration, peribronchiolar fibrosis, and mucus exacerbation caused by the allergen challenge. Ac2-26 also inhibited AHR and mediator production. Collectively, our findings show that the AnxA1-derived peptide Ac2-26 protects against several pathological changes associated with HDM allergic reaction, suggesting that this peptide or related AnxA1-mimetic Ac2-26 may represent promising therapeutic candidates for the treatment of allergic asthma. Full article

Reprimo-like (RPRML) is an uncharacterized member of the Reprimo gene family. Here, we evaluated the role of RPRML and whether its regulation by DNA methylation is a potential non-invasive biomarker of gastric cancer. RPRML expression was evaluated by immunohistochemistry in 90 patients with gastric cancer and associated with clinicopathologic characteristics and outcomes. The role of RPRML in cancer biology was investigated in vitro, through RPRML ectopic overexpression. Functional experiments included colony formation, soft agar, MTS, and Ki67 immunofluorescence assays. DNA methylation-mediated silencing was evaluated by the 5-azacytidine assay and direct bisulfite sequencing. Non-invasive detection of circulating methylated RPRML DNA was assessed in 25 gastric cancer cases and 25 age- and sex-balanced cancer-free controls by the MethyLight assay. Downregulation of RPRML protein expression was associated with poor overall survival in advanced gastric cancer. RPRML overexpression significantly inhibited clonogenic capacity, anchorage-independent growth, and proliferation in vitro. Circulating methylated RPRML DNA distinguished patients with gastric cancer from controls with an area under the curve of 0.726. The in vitro overexpression results and the poor patient survival associated with lower RPRML levels suggest that RPRML plays a tumor-suppressive role in the stomach. Circulating methylated RPRML DNA may serve as a biomarker for the non-invasive detection of gastric cancer. Full article