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Advances in the approaches used to repurpose drugs for neuroblastoma.
No full text20.500.12530/87857Neuroblastoma (NB) remains a challenging pediatric malignancy with limited treatment options, particularly for high-risk cases. Drug repurposing offers a convenient and cost-effective strategy for treating rare diseases like NB. Using existing drugs with known safety profiles accelerates the availability of new treatments, reduces development costs, and mitigates risks, offering hope for improved patient outcomes in challenging conditions. This review provides an overview of the advances in approaches used to repurpose drugs for NB therapy. The authors discuss strategies employed in drug repurposing, including computational and experimental methods, and rational drug design, highlighting key examples of repurposed drugs with promising clinical results. Additionally, the authors examine the challenges and opportunities associated with drug repurposing in NB and discuss future directions and potential areas for further research. The fact that only one new drug has been approved in the last 30 years for the treatment of neuroblastoma plus a significant proportion of high-risk NB patients that remain uncurable, evidences the need for new fast and cost-effective alternatives. Drug repurposing may accelerate the treatment development process while reducing expenses and risks. This approach can swiftly bring effective NB therapies to market, enhancing survival rates and patient quality of life
Vascular Calcification: Molecular Networking, Pathological Implications and Translational Opportunities.
No full text20.500.12530/87887Calcification is a process of accumulation of calcium in tissues and deposition of calcium salts by the crystallization of PO43- and ionized calcium (Ca2+). It is a crucial process in the development of bones and teeth. However, pathological calcification can occur in almost any soft tissue of the organism. The better studied is vascular calcification, where calcium salts can accumulate in the intima or medial layer or in aortic valves, and it is associated with higher mortality and cardiovascular events, including myocardial infarction, stroke, aortic and peripheral artery disease (PAD), and diabetes or chronic kidney disease (CKD), among others. The process involves an intricate interplay of different cellular components, endothelial cells (ECs), vascular smooth muscle cells (VSMCs), fibroblasts, and pericytes, concurrent with the activation of several signaling pathways, calcium, Wnt, BMP/Smad, and Notch, and the regulation by different molecular mediators, growth factors (GFs), osteogenic factors and matrix vesicles (MVs). In the present review, we aim to explore the cellular players, molecular pathways, biomarkers, and clinical treatment strategies associated with vascular calcification to provide a current and comprehensive overview of the topic
Recommendations on the treatment of metastatic hormone-sensitive prostate cancer: Patient selection.
No full textThe standard treatment for metastatic hormone-sensitive prostate cancer (mHSPC) is now a combination of androgen deprivation therapy plus an androgen receptor-targeted therapy (abiraterone, apalutamide, enzalutamide or darolutamide), with or without chemotherapy (docetaxel). The selection of suitable patients for each therapeutic approach has become a determining factor to ensure efficacy and minimize side effects. This article combines recent clinical evidence with the accumulated experience of experts in medical oncology, radiation oncology and urology, to provide a comprehensive view and therapeutic recommendations for mHSPC
ProsTAV, a clinically useful test in prostate cancer: an extension study.
No full text20.500.12530/87852To assess the clinical performance of ProsTAV®, a blood-based test based on telomere associate variables (TAV) measurement, to support biopsy decision-making when diagnosing suspicious prostate cancer (PCa). Preliminary data of a prospective observational pragmatic study of patients with prostate-specific antigen (PSA) levels 3-10 ng/ml and suspicious PCa. Results were combined with other clinical data, and all patients underwent prostate biopsies according to each center's routine clinical practice, while magnetic resonance imaging (MRI) before the prostate biopsy was optional. Sensitivity, specificity, positive and negative predicted values, and subjects where biopsies could have been avoided using ProsTAV were determined. The mean age of the participants (n = 251) was 67.4 years, with a mean PSA of 5.90 ng/ml, a mean free PSA of 18.9%, and a PSA density of 0.14 ng/ml. Digital rectal examination was abnormal in 21.1% of the subjects, and according to biopsy, the prevalence of significant PCa was 47.8%. The area under the ROC curve of ProsTAV was 0.7, with a sensitivity of 0.90 (95% CI, 0.85-0.95) and specificity of 0.27 (95% CI, 0.19-0.34). The positive and negative predictive values were 0.53 (95% CI, 0.46-0.60) and 0.74 (95% CI, 0.62-0.87), respectively. ProsTAV could have reduced the biopsies performed by 27% and showed some initial evidence of a putative benefit in the diagnosis pathway combined with MRI. ProsTAV increases the prediction capacity of significant PCa in patients with PSA between 3 and 10 ng/ml and could be considered a complementary tool to improve the patient diagnosis pathway
Emergency psychiatric care for children and adolescents: factors associated with multiple visits and hospital admissions.
No full textGiven the increased demand for mental health resources in the child and adolescent population, this study aims to describe the emergency psychiatric care of the children and adolescents and to explore factors associated with multiple visits and hospital admissions. All patients
Patterns of First Recurrence and Oncological Outcomes in Locally Advanced Cervical Cancer Patients: Does Surgical Staging Play a Role?
No full text20.500.12530/87857We aimed to determine whether surgical aortic staging by minimally invasive paraaortic lymphadenectomy (PALND) affects the pattern of first recurrence and survival in treated locally advanced cervical cancer (LACC) patients when compared to patients staged by imaging (noPALND). This study was a multicenter observational retrospective cohort study of patients with LACC treated at tertiary care hospitals throughout Spain. The inclusion criteria were histological diagnosis of squamous carcinoma, adenosquamous carcinoma, and/or adenocarcinoma; FIGO stages IB2, IIA2-IVA (FIGO 2009); and planned treatment with primary chemoradiotherapy between 2000 and 2016. Propensity score matching (PSM) was performed before the analysis. After PSM and sample replacement, 1092 patients were included for analysis (noPALND n = 546, PALND n = 546). Twenty-one percent of patients recurred during follow-up, with the PALND group having almost double the recurrences of the noPALND group (noPALND: 15.0%, PALND: 28.0%, p After treatment, surgically staged patients with LACC recurred more frequently and showed worse survival rates
Training in cataract surgery in Spain: analysis of the results of a survey of the European Board of Ophthalmology in a Spanish cohort.
No full text20.500.12530/87908A survey conducted by the European Board of Ophthalmology (EBO) revealed significant differences in the surgical training of the ophthalmology residents in Europe, including a disparity between the sexes and a variation in the experience on cataract surgery (CC) between them. This study is about the Spanish sub-cohort of the survey, and its objective is to present and analyse the peculiarities of ophthalmology training in Spain within the European context, as well as discussing ways to harmonise and improve that training throughout the EU. We analyse data of the Spanish participants in the EBO exams, defining subgroups by the Autonomous Communities existing in Spain. 93 of 135 requested participants (68.9%) responded. A 60.2% passed the EBO exam between 2021 and 2022, being mostly women (65.59%) aged 31 years old on average. The 91.4% were right-handed, coming from 13 of the 17 Spanish autonomous communities, although mostly from the Community of Valencia, Madrid and Catalonia. Respectively, 16.1%, 3.2% and 8.7% of the respondents said they have completed 10 or more training sessions on animal eyes, synthetic eyes and through the virtual reality simulator. This training was correlated with greater self-confidence in the management of a posterior capsular tear during surgery (p .025). All respondents manifested to have already performed stages of the CC. The average number of operations reported was 181.6 with regional disparities. A significant difference is observed between the sexes against women (-28.3%, p 0.03). Ophthalmologists in Spain, much more than other European countries, have greater opportunities for surgical training, with surgical procedures during the residency, that nearly triples those made by the others. Spanish women refer, like their European colleagues, to be in disadvantage in learning opportunities about cataract surgery. The Simulation Based Medical Education (SBME) allows to respond to the training deficit and complements the training on the patient. Although we demonstrate a significant correlation between the number of procedures carried out and self-confidence to operate simple cases, the SBME would be a complementary tool in self-confidence in front of a complication like capsular rupture. Spain massively adopts the model named by us "surgery for all", despite the underrepresentation of women in this area, emphasising a need for cultural change that the SBME could facilitate
Effect of a Health Education Intervention to Reduce Fear of Falling and Falls in Older People: A Cluster Randomized Clinical Trial Protocol.
No full text20.500.12530/87857Background/Objectives: Fear of falling (FOF) and falls are prevalent issues among older adults, leading to activity restriction, decreased quality of life, and increased dependency. This study aims to assess the effectiveness of a nurse-led health education intervention to reduce FOF and fall incidence in older adults within primary care settings. Methods: This two-arm, multicenter, parallel, cluster-randomized clinical trial includes ten primary care centers in Spain and will enroll 150 adults over 65 years with FOF, mild or no functional dependence, and independent ambulation. Participants will be randomized to either the intervention group, which will receive five initial group education sessions led by community nurses and a booster session at six months, or the control group, which will receive usual care. Primary outcomes include FOF, assessed using the Short Falls Efficacy Scale-International (FES-I), and fall incidence. Data collection will occur at baseline, one month, six months, and twelve months post intervention. This study has been approved by the Ethics Committee for Research with Medicinal Products at Gregorio Marañón University Hospital in accordance with the Declaration of Helsinki. Expected Outcomes: The health education intervention is expected to significantly reduce both FOF and fall incidence, supporting the integration of FOF management in routine primary care for older adults, with potential benefits for safety and quality of life. Trial Registration: ClinicalTrials.gov: NCT05889910. The study protocol follows CONSORT and SPIRIT guidelines
Quantification of human immunodeficiency virus type 2 (HIV-2) viral load in plasma: Comparison of three commercial assays.
No full textThere are few validated commercially available HIV-2 assays for the measurement of viral load. Our aim was to compare three commercial assays for the quantification of HIV-2 viral load in plasma of patients with HIV-2 infection from our hospital. We conducted a retrospective study at our tertiary-care hospital, analyzing samples from patients with known HIV-2 infection collected between 2022 and 2023. We compared three commercial assays for quantification of the viral load, Biomérieux® NASBA assay, Thermo Fisher® digital PCR (dPCR) assay and Altona® RT-PCR assay. A total of 27 samples from 11 different patients were included in the study. Sixteen out of them were negative across all three assays. One sample had a low viral load ( The Altona® RT-PCR assay and the ThermoFisher® dPCR assay could be reliable options as commercial assays for the quantification of HIV-2 RNA in plasma. However, the Biomérieux® NASBA assay, despite detecting both HIV-1 and HIV-2, may have limitations for HIV-2 detection in some cases
Long-Term Survival of Subcutaneous Biosimilar Tumor Necrosis Factor Inhibitors Compared to Originators: Results From a Multicenter Prospective Registry.
No full text20.500.12530/87910To analyze the long-term survival of subcutaneous biosimilar tumor necrosis factor inhibitors compared to the originator molecules in patients with rheumatic diseases, as well as the factors associated with drug discontinuation. Retrospective analysis of BIOBADASER, the Spanish multicenter prospective registry of patients with rheumatic disease receiving biologic and targeted disease-modifying antirheumatic drugs. Patients who started etanercept (ETN) or adalimumab (ADA) from January 2016 to October 2023 were included. The survival probabilities of biosimilars and originators were compared using Kaplan-Meier estimating curves. To identify factors associated with differences in the retention rates, hazard ratios (HR) were estimated using Cox regression models for all and specific causes (inefficacy or adverse events [AEs]) of discontinuation. A total of 4162 patients received 4723 treatment courses (2991 courses of ADA and 1732 courses of ETN), of which 722 (15.29%) were with originator molecules and 4001 (84.71%) were with biosimilars. The originators were more frequently discontinued than biosimilars (53.32% vs 33.37%, respectively). The main reason for discontinuation was inefficacy (60.35% of the treatments). The risk of overall discontinuation was lower for biosimilars (adjusted HR 0.84, 95% CI 0.75-0.95). Female sex, obesity, and second or later treatment lines increased the risk of discontinuation, whereas disease duration and the use of concomitant methotrexate were associated with a greater survival. When assessing cause-specific reasons of discontinuation, excluding nonmedical switching, the results from the crude and adjusted analyses showed no significant differences in the retention rate between biosimilars and originators. No significant differences were found between treatments in long-term survival due to inefficacy or AEs