Eventos adversos y complicaciones del tratamiento antineoplásico administrados durante la infancia

El cáncer infantil es una enfermedad crónica potencialmente mortal, la cual representa un gran impacto no solo para los pacientes, sino para su familia. El niño con cáncer debe enfrentarse al impacto emocional, físico, social, psicológico y a los efectos de la enfermedad y su tratamiento. Se considera que uno de cada 640 adultos jóvenes entre las edades de 20 y 39 años presentaron cáncer en su infancia, esto sumado al aumento de sobrevida debido a los tratamientos actuales, hace que las complicaciones que se puedan presentar en el tratamiento o por su enfermedad sean un marcador de morbimortalidad a largo plazo. Por tal motivo, el niño con cáncer debe hacer frente a los cambios adquiridos y a las complicaciones de la enfermedad y su tratamiento. Todos estos factores pueden poner en peligro la calidad de vida del niño con diagnóstico de cáncer y hacer más difícil el cumplimiento del régimen de terapia antineoplásica propuesto. El objetivo de este artículo es hacer una revisión de las principales complicaciones y efectos adversos que pueden ocurrir en pacientes que son sometidos a tratamientos antineoplásicos detallando las complicaciones por sistemas, las complicaciones propias de los medicamentos y los eventos adversos ocurridos por la atención a estos pacientes. MÉD.UIS. 2014;27(3):77-88.Childhood cancer is a life-threatening chronic disease, which represents a great impact not only for patients, but for their family. The child with cancer must face the emotional, physical, social, and psychological effects of the disease and its treatment impact. It is believed that 1 in every 640 young adults between the ages of 20 and 39 years had cancer in their infancy, this added to increased survival due to current treatments, causes complications that may arise in the treatment or their disease be a marker of long-term morbidity. Therefore children with cancer must face the acquired changes and complications of the disease and its treatment. All these factors can impair the quality of life of children with cancer diagnosis and ensure implementation of the proposed scheme antineoplastic therapy more difficult. The aim of this article is to review major complications and side effects that can occur in patients who are undergoing cancer treatments detailing complications systems, the complications of drugs and adverse events that occurred in the care of these patients. MÉD.UIS. 2014;27(3):77-88

Síndrome de Werdnig-Hoffmann (atrofia muscular espinal de la infancia). Presentación de un caso y revisión en la literatura

El síndrome de Werdnig-Hoffmann o atrofia muscular espinal (AME)  de  la  infancia  es  una  enfermedad  de  patrón autosómico  recesivo de origen neuromuscular y degenerativo, poco prevalente en  la población general, y que se caracteriza por la destrucción de las neuronas motoras del asta anterior de la medula espinal debido a alteraciones cromosómicas. La enfermedad no tiene tratamiento, es de mal pronóstico y, por  lo general,  culmina  con  la  muerte  del  menor  en  los primeros años de vida por dificultad respiratoria, infecciones respiratorias o ambas. En el presente artículo se describe un caso de  la enfermedad que se pone en evidencia con el árbol genealógico en el que se encuentra el patrón de herencia de la  enfermedad, además  de  los  síntomas  y  signos  que  la caracterizan

Girls4STEM: gender diversity in STEM for a sustainable future

Science, Technology, Engineering, and Mathematics (STEM) are key disciplines towards tackling the challenges related to the Sustainable Development Goals. However, evidence shows that women are enrolling in these disciplines in a smaller percentage than men, especially in Engineering related fields. As stated by the United Nations Women section, increasing the number of women studying and working in STEM fields is fundamental towards achieving better solutions to the global challenges, since the potential for innovation is larger. In this paper, we present the Girls4STEM project, which started in 2019 at the Escola Tècnica Superior d'Enginyeria de la Universitat de València, Spain. This project works towards breaking the stereotypes linked to STEM fields, addressing both boys and girls aged from 6 to 18, but especially trying to open the range of career options for young girls through interaction with female STEM experts. The goal is to spark girls' interest in STEM disciplines from childhood, so that they become more self-confident in these areas. To achieve this goal, the project is built over three main actions: the Girls4STEM Family Talks, where students, families, and teachers participate; the Girls4STEM Professional Talks, where the target is a general audience; and the Initial Training Seminars for teachers. Short-term results are here presented, showing that aspects related to self-perception and perception from others (family, teachers) play a significant role. Moreover, these results also indicate that there may not be a general understanding of which disciplines are included in STEM

Mutational spectrum of GNAL, THAP1 and TOR1A genes in isolated dystonia: study in a population from Spain and systematic literature review

[Objective] We aimed to investigate the prevalence of TOR1A, GNAL and THAP1 variants as the cause of dystonia in a cohort of Spanish patients with isolated dystonia and in the literature.[Methods] A population of 2028 subjects (including 1053 patients with different subtypes of isolated dystonia and 975 healthy controls) from southern and central Spain was included. The genes TOR1A, THAP1 and GNAL were screened using a combination of high-resolution melting analysis and direct DNA resequencing. In addition, an extensive literature search to identify original articles (published before 10 August 2020) reporting mutations in TOR1A, THAP1 or GNAL associated to dystonia was performed.[Results] Pathogenic or likely pathogenic variants in TOR1A, THAP1 and GNAL were identified in 0.48%, 0.57% and 0.29% of our patients, respectively. Five patients carried the variation p.Glu303del in TOR1A. A very rare variant in GNAL (p.Ser238Asn) was found as a putative risk factor for dystonia. In the literature, variations in TOR1A, THAP1 and GNAL accounted for about 6%, 1.8% and 1.1% of published dystonia patients, respectively.[Conclusions] There is a different genetic contribution to dystonia of these three genes in our patients (about 1.3% of patients) and in the literature (about 3.6% of patients), probably due the high proportion of adult-onset cases in our cohort. As regards age at onset, site of dystonia onset, and final distribution, in our population there is a clear differentiation between DYT-TOR1A and DYT-GNAL, with DYT-THAP1 likely to be an intermediate phenotype.This work was supported by the Carlos III Health Institute-European Regional Development Fund (ISCIII-FEDER) [PI14/01823, PI16/01575, PI18/01898, PI19/01576], the Andalusian Regional Ministry of Economics, Innovation, Science and Employment [CVI-02526, CTS-7685], the Andalusian Regional Ministry of Health and Welfare [PI-0741-2010, PI-0471-2013, PE-0210-2018, PI-0459-2018, PE-0186-2019], and the Alicia Koplowitz and Mutua Madrileña Foundations. Pilar Gómez-Garre was supported by the "Miguel Servet" program [MSII14/00018] (from ISCIII-FEDER) and “Nicolás Monardes” program [C-0048-2017] (from the Andalusian Regional Ministry of Health). Silvia Jesús was supported by the "Juan Rodés" program [B-0007-2019] and Daniel Macías-García by the “Río Hortega” program [CM18/00142] (both from ISCIII-FEDER). María Teresa Periñán was supported by the Spanish Ministry of Education [FPU16/05061]. Cristina Tejera was supported by VPPI-US from the University of Seville.Peer reviewe

Chemotherapy or allogeneic transplantation in high-risk Philadelphia chromosome–negative adult lymphoblastic leukemia

The need for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adults with Philadelphia chromosome–negative (Ph−) acute lymphoblastic leukemia (ALL) with high-risk (HR) features and adequate measurable residual disease (MRD) clearance remains unclear. The aim of the ALL-HR-11 trial was to evaluate the outcomes of HR Ph− adult ALL patients following chemotherapy or allo-HSCT administered based on end-induction and consolidation MRD levels. Patients aged 15 to 60 years with HR-ALL in complete response (CR) and MRD levels (centrally assessed by 8-color flow cytometry) <0.1% after induction and <0.01% after early consolidation were assigned to receive delayed consolidation and maintenance therapy up to 2 years in CR. The remaining patients were allocated to allo-HSCT. CR was attained in 315/348 patients (91%), with MRD <0.1% after induction in 220/289 patients (76%). By intention-to-treat, 218 patients were assigned to chemotherapy and 106 to allo-HSCT. The 5-year (±95% confidence interval) cumulative incidence of relapse (CIR), overall survival (OS), and event-free survival probabilities for the whole series were 43% ± 7%, 49% ± 7%, and 40% ± 6%, respectively, with CIR and OS rates of 45% ± 8% and 59% ± 9% for patients assigned to chemotherapy and of 40% ± 12% and 38% ± 11% for those assigned to allo-HSCT, respectively. Our results show that avoiding allo-HSCT does not hamper the outcomes of HR Ph− adult ALL patients up to 60 years with adequate MRD response after induction and consolidation. Better postremission alternative therapies are especially needed for patients with poor MRD clearance

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Regulatory sites for splicing in human basal ganglia are enriched for disease-relevant information

Genome-wide association studies have generated an increasing number of common genetic variants associated with neurological and psychiatric disease risk. An improved understanding of the genetic control of gene expression in human brain is vital considering this is the likely modus operandum for many causal variants. However, human brain sampling complexities limit the explanatory power of brain-related expression quantitative trait loci (eQTL) and allele-specific expression (ASE) signals. We address this, using paired genomic and transcriptomic data from putamen and substantia nigra from 117 human brains, interrogating regulation at different RNA processing stages and uncovering novel transcripts. We identify disease-relevant regulatory loci, find that splicing eQTLs are enriched for regulatory information of neuron-specific genes, that ASEs provide cell-specific regulatory information with evidence for cellular specificity, and that incomplete annotation of the brain transcriptome limits interpretation of risk loci for neuropsychiatric disease. This resource of regulatory data is accessible through our web server, http://braineacv2.inf.um.es/

Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: a meta-analysis of genome-wide association studies

Background Genome-wide association studies (GWAS) in Parkinson's disease have increased the scope of biological knowledge about the disease over the past decade. We aimed to use the largest aggregate of GWAS data to identify novel risk loci and gain further insight into the causes of Parkinson's disease. Methods We did a meta-analysis of 17 datasets from Parkinson's disease GWAS available from European ancestry samples to nominate novel loci for disease risk. These datasets incorporated all available data. We then used these data to estimate heritable risk and develop predictive models of this heritability. We also used large gene expression and methylation resources to examine possible functional consequences as well as tissue, cell type, and biological pathway enrichments for the identified risk factors. Additionally, we examined shared genetic risk between Parkinson's disease and other phenotypes of interest via genetic correlations followed by Mendelian randomisation. Findings Between Oct 1, 2017, and Aug 9, 2018, we analysed 7·8 million single nucleotide polymorphisms in 37 688 cases, 18 618 UK Biobank proxy-cases (ie, individuals who do not have Parkinson's disease but have a first degree relative that does), and 1·4 million controls. We identified 90 independent genome-wide significant risk signals across 78 genomic regions, including 38 novel independent risk signals in 37 loci. These 90 variants explained 16–36% of the heritable risk of Parkinson's disease depending on prevalence. Integrating methylation and expression data within a Mendelian randomisation framework identified putatively associated genes at 70 risk signals underlying GWAS loci for follow-up functional studies. Tissue-specific expression enrichment analyses suggested Parkinson's disease loci were heavily brain-enriched, with specific neuronal cell types being implicated from single cell data. We found significant genetic correlations with brain volumes (false discovery rate-adjusted p=0·0035 for intracranial volume, p=0·024 for putamen volume), smoking status (p=0·024), and educational attainment (p=0·038). Mendelian randomisation between cognitive performance and Parkinson's disease risk showed a robust association (p=8·00 × 10−7). Interpretation These data provide the most comprehensive survey of genetic risk within Parkinson's disease to date, to the best of our knowledge, by revealing many additional Parkinson's disease risk loci, providing a biological context for these risk factors, and showing that a considerable genetic component of this disease remains unidentified. These associations derived from European ancestry datasets will need to be followed-up with more diverse data. Funding The National Institute on Aging at the National Institutes of Health (USA), The Michael J Fox Foundation, and The Parkinson's Foundation (see appendix for full list of funding sources)

Ciencia Odontológica 2.0

Libro que muestra avances de la Investigación Odontológica en MéxicoEs para los integrantes de la Red de Investigación en Estomatología (RIE) una enorme alegría presentar el segundo de una serie de 6 libros sobre casos clínicos, revisiones de la literatura e investigaciones. La RIE está integrada por cuerpos académicos de la UAEH, UAEM, UAC y UdeG

Eventos adversos y complicaciones del tratamiento antineoplásico administrados durante la infancia

AbstractChildhood cancer is a life-threatening chronic disease, which represents a great impact not only for patients, but for their family. The child with cancer must face the emotional, physical, social, and psychological effects of the disease and its treatment impact. It is believed that 1 in every 640 young adults between the ages of 20 and 39 years had cancer in their infancy, this added to increased survival due to current treatments, causes complications that may arise in the treatment or their disease be a marker of long-term morbidity. Therefore children with cancer must face the acquired changes and complications of the disease and its treatment. All these factors can impair the quality of life of children with cancer diagnosis and ensure implementation of the proposed scheme antineoplastic therapy more difficult. The aim of this article is to review major complications and side effects that can occur in patients who are undergoing cancer treatments detailing complications systems, the complications of drugs and adverse events that occurred in the care of these patients. MÉD.UIS. 2014;27(3):77-88.Keywords: Antineoplastic protocols. Radiation oncology. Neoplasm metastasis. Neoplasm, Residual. Neoplasm invasiveness. Drug therapy. Febrile neutropenia.ResumenEl cáncer infantil es una enfermedad crónica potencialmente mortal, la cual representa un gran impacto no solo para los pacientes, sino para su familia. El niño con cáncer debe enfrentarse al impacto emocional, físico, social, psicológico y a los efectos de la enfermedad y su tratamiento. Se considera que uno de cada 640 adultos jóvenes entre las edades de 20 y 39 años presentaron cáncer en su infancia, esto sumado al aumento de sobrevida debido a los tratamientos actuales, hace que las complicaciones que se puedan presentar en el tratamiento o por su enfermedad sean un marcador de morbimortalidad a largo plazo. Por tal motivo, el niño con cáncer debe hacer frente a los cambios adquiridos y a las complicaciones de la enfermedad y su tratamiento. Todos estos factores pueden poner en peligro la calidad de vida del niño con diagnóstico de cáncer y hacer más difícil el cumplimiento del régimen de terapia antineoplásica propuesto. El objetivo de este artículo es hacer una revisión de las principales complicaciones y efectos adversos que pueden ocurrir en pacientes que son sometidos a tratamientos antineoplásicos detallando las complicaciones por sistemas, las complicaciones propias de los medicamentos y los eventos adversos ocurridos por la atención a estos pacientes. MÉD.UIS. 2014;27(3):77-88.Palabras clave: Protocolos antineoplásicos. Oncología por radiación. Metástasis de la neoplasia. Neoplasia residual.Invasividad neoplásica. Quimioterapia. Neutropenia febril