Relación entre el tamaño de deleción y afectación del lenguaje en síndrome de Phelan-McDermid: revisión sistemática

Background and aims: The Phelan-McDermid syndrome is a rare disease with an unknown prevalence produced by a neurodevelopmental disorder which causes the loss in the function of the SHANK3 gene, entailing a great variety of clinic symptoms, mostly linguistic alterations, and even been absent in a large number of subjects. The following revision consisted in a systematic review, whose main objective focused on assessing the existence of a correlation between the size of the 22q13 deletion, and the development or affectation of the language in subjects between 0 and 55 years old, suffering from the Phelan-McDermid syndrome. Method: for the completion of the following paper, research was conducted on the matter of fact in articles published on PubMed, Medline, Cochrane Plus, Psycinfo and Google Scholar, between 2010 and March 2020. Finally, this systematic revision was conducted with the content of the complete text of 8 articles. Results: the results indicated the existence, on a significant scale, of a correlation between the size of the 22q13 deletion and language the absence or disruption in patients with the Phelan-McDermid syndrome. Conclusions: not with standing, it is required from further research on the topic to determine and understand such correlation in-depth.Antecedentes y objetivo: el Síndrome Phelan-McDermid es una enfermedad rara con prevalencia desconocida, provocada por un desorden del neurodesarrollo que genera la pérdida de la función del gen SHANK3, ocasionando una gran variedad de síntomas clínicos, sobre todo alteraciones lingüísticas, incluso pudiendo estar ausente en una gran cantidad de sujetos. Este trabajo consistió en una revisión sistemática, cuyo objetivo se centró en valorar la existencia de una correlación entre el tamaño de la deleción 22q13 y el desarrollo o afectación del lenguaje en sujetos entre 0 y 55 años con Síndrome Phelan-McDermid. Método: para realizar el presente trabajo, se realizó una búsqueda en PubMed, Medline, Cochrane Plus, PsycInfo y Google Académico de artículos publicados sobre el tema en cuestión, entre los años 2010 y marzo del 2020. Finalmente, esta revisión sistemática se realizó con el contenido de 8 artículos a texto completo. Resultados: los resultados indicaron la existencia, de forma significativa, de la correlación entre el tamaño de la deleción 22q13 y la ausencia o alteración del lenguaje en pacientes con Síndrome Phelan-McDermid. Conclusiones: no obstante, se precisa de investigaciones futuras sobre el tema, para determinar y conocer en profundidad dicha relación

Vigilancia de Dióxido de Azufre y Dióxido de Nitrógeno en la Estación de Centro Habana. 2001-2003

Estudios previos han reportado altas concentraciones de contaminantesatmosféricos en Centro Habana, asociadas a un mayor riesgo de enfermedadesrespiratorias y alérgicas. Con el objetivo de describir la contaminación atmosférica enCentro Habana y sus posibles riesgos para la salud, se realizó un estudio descriptivo delcomportamiento de las concentraciones diarias de dióxido de azufre (SO2), dióxido denitrógeno (NO2) e índice de acidez en el periodo de octubre del 2001 a octubre del2003. Las bases de datos fueron confeccionadas en dBase y EXCEL y procesadasmediante Epi Info v. 2.6 y SPSS v. X. El análisis estadístico incluyó valores detendencia central, porcentajes de trasgresión de las concentraciones máximasadmisibles (CMA), valores máximos y percentiles 25, 75 y 95. Se evaluó la correlaciónentre contaminantes mediante el coeficiente rho de Spearman. Se construyeronmodelos de regresión lineal múltiple para cada contaminante y las variablesmeteorológicas seleccionadas. Las concentraciones medias diarias de acidez, SO2 yNO2 resultaron inferiores a las CMA. Se observaron correlaciones directas moderadasentre todos los contaminantes, más fuerte entre el SO2 y la acidez

Reporte del monitoreo ambiental en el marco de la supervisión regular a la Municipalidad Provincial de Chincha - Botadero de Residuos Sólidos Municipales Chincha; ubicado en el distrito Chincha Alta, provincia Chincha, departamento lca, llevado a cabo del 02 al 06 de junio 2014.

Presenta el reporte del Monitoreo Ambiental realizado en el marco de la supervisión regular a la Municipalidad Provincial de Chincha - Botadero de Residuos Sólidos Municipales de Chincha; ubicado en el distrito Chincha Alta, provincia Chincha, departamento lca, llevado a cabo del 2 al 6 de junio de 2014. Además de los residuos domésticos municipales se observó dentro del botadero residuos hospitalarios y desmonte. Esta ficha no incluye los resultados analíticos del monitoreo ambiental. Contiene los siguientes anexos: copia de cadena de custodia con sello de recepción del laboratorio y registro fotográfico

Reporte del monitoreo ambiental en el marco de la supervisión regular a la Municipalidad Provincial de Pasco- Botadero de Residuos Sólidos Municipales Rumiallana; ubicado en el distrito Yanacancha, provincia Cerro de Pasco, departamento Pasco, llevado a cabo del 21 al 24 de abril 2014.

Presenta los reportes del monitoreo ambiental realizado en el marco de la supervisión regular a la Municipalidad Provincial de Pasco - Botadero de Residuos Sólidos Municipales Rumiallana; ubicado en el distrito Yanacancha, provincia Cerro de Pasco, departamento Pasco, llevado a cabo el 21 al 24 de abril de 2014. La toma de muestras de aguas residuales industriales se realizó de acuerdo al Protocolo para Monitoreo de Efluentes Líquidos y Emisiones, aprobado por Resolución Ministerial W 026-2000- ITINCI-DM, que aprueba el Protocolo de Monitoreo de Efluentes Líquidos del Sector Industrial. Esta ficha no incluye los resultados analíticos del monitoreo ambiental. Contiene los siguientes anexos: registro fotográfico, copia de certificado de calibración de equipo potenciómetro, y copia de cadena de custodia con sello de recepción del laboratorio

Skin autofluorescence–indicated advanced glycation end products as predictors of cardiovascular and all-cause mortality in high-risk subjects: a systematic review and meta-analysis

Background Chronic deposits of advanced glycation end products produced by enzymatic glycation have been suggested as predictors of atherosclerotic-related disorders. This study aimed to estimate the relationship between advanced glycation end products indicated by skin autofluorescence levels and the risk of cardiovascular and all-cause mortality based on data from observational studies. Methods and Results We systematically searched Medline, Embase, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and the Web of Science databases from their inceptions until November 2017 for observational studies addressing the association of advanced glycation end products by skin autofluorescence levels with cardiovascular and all-cause mortality. The DerSimonian and Laird random-effects method was used to compute pooled estimates of hazard ratios and their respective 95% confidence intervals for the risk of cardiovascular and all-cause mortality associated with levels of advanced glycation end products by skin autofluorescence. Ten published studies were included in the systematic review and meta-analysis. Higher skin autofluorescence levels were significantly associated with a higher pooled risk estimate for cardiovascular mortality (hazard ratio: 2.06; 95% confidence interval, 1.58-2.67), which might not be important to moderate heterogeneity (I2=34.7%; P=0.163), and for all-cause mortality (hazard ratio: 1.91; 95% confidence interval, 1.42-2.56) with substantial heterogeneity (I2=60.8%; P=0.0.18). Conclusions Our data suggest that skin autofluorescence levels could be considered predictors of all-cause mortality and cardiovascular mortality in patients at high and very high risk.Cavero-Redondo and Martínez-Hortelano are supported by a grant from the Universidad de Castilla-La Mancha (FPU13/ 01582 and PREDUCLM16/14, respectively). Soriano-Cano is supported by a grant from Spanish Ministry of Economy, Industry, and Competitiveness (Fi 17/332). Garrido-Miguel and Berlanga-Macías are supported by a grant from the Spanish Ministry of Education, Culture, and Sport (FPU15/ 03847 and FPU16/02380, respectively).info:eu-repo/semantics/publishedVersio

Case Report: A Case Study Documenting the Activity of Atezolizumab in a PD-L1-Negative Triple-Negative Breast Cancer

Biomarcadores; Cáncer de mama; InmunoterapiaBiomarcadors; Càncer de mama; ImmunoteràpiaBiomarkers; Breast cancer; ImmunotherapyThe immune checkpoint inhibitor atezolizumab is approved for PD-L1-positive triple-negative breast cancer (TNBC). However, no activity of atezolizumab in PD-L1-negative TNBC has been reported to date. Here, we present the case study of a woman with TNBC with low tumor infiltrating lymphocytes and PD-L1-negative disease, which achieved a significant response to atezolizumab monotherapy and durable response after the combination of atezolizumab and nab-paclitaxel. The comprehensive genomic analysis that we performed in her tumor and plasma samples revealed high tumor mutational burden (TMB), presence of the APOBEC genetic signatures, high expression of the tumor inflammation signature, and a HER2-enriched subtype by the PAM50 assay. Some of these biomarkers have been shown to independently predict response to immunotherapy in other tumors and may explain the durable response in our patient. Our work warrants further translational studies to identify biomarkers of response to immune checkpoint inhibitors in TNBC beyond PD-L1 expression and to better select patients that will benefit from immunotherapy.This study has received funding from Instituto de Salud Carlos III—PI19/01846 (to AP), Breast Cancer Now—2018NOVPCC1294 (to AP), Breast Cancer Research Foundation-AACR Career Development Awards for Translational Breast Cancer Research 19-20-26-PRAT (to AP), Fundació La Marató TV3 201935-30 (to AP), the European Union’s Horizon 2020 research and innovation programme H2020-SC1-BHC-2018-2020 (to AP), Asociación de Cáncer de Mama Metastásico CMM_CHIARAG19_001 (to AP), Pas a Pas (to AP), Save the Mama (to AP), Fundación Científica Asociación Española Contra el Cáncer AECC_Postdoctoral17-1062 (to FB-M) and INVES19056SANS (to MiS), FERO-ghd 2020 breast cancer award (MS), and Generalitat de Catalunya Peris PhD4MD 2019 SLT008/18/00122 (to NC)

Early-Stage Breast Cancer Detection in Breast Milk

Breast cancer; Breast milkCáncer de mama; Leche maternaCàncer de mama; Llet maternaBreast cancer occurring during pregnancy (PrBC) and postpartum (PPBC) is usually diagnosed at more advanced stages compared with other breast cancer, worsening its prognosis. PPBC is particularly aggressive, with increased metastatic risk and mortality. Thus, effective screening methods to detect early PrBC and PPBC are needed. We report for the first time that cell-free tumor DNA (ctDNA) is present in breast milk (BM) collected from patients with breast cancer. Analysis of ctDNA from BM detects tumor variants in 87% of the cases by droplet digital PCR, while variants remain undetected in 92% of matched plasma samples. Retrospective next-generation sequencing analysis in BM ctDNA recapitulates tumor variants, with an overall clinical sensitivity of 71.4% and specificity of 100%. In two cases, ctDNA was detectable in BM collected 18 and 6 months prior to standard diagnosis. Our results open up the potential use of BM as a new source for liquid biopsy for PPBC detection. Significance: For the first time, we show that BM obtained from patients with breast cancer carries ctDNA, surpassing plasma-based liquid biopsy for detection and molecular profiling of early-stage breast cancer, even prior to diagnosis by image.We thank the patients who participated in the study and donated samples for analysis for their generous contribution, with particular thanks to the first patient, Maite, and her daughter Àneu, who inspired us to initiate this study (oral consent to name the patient and her daughter was provided by the patient, and her legal partner provided written consent after patient's exitus). We are grateful to Javier Carmona for his valuable contributions and support in the manuscript's conceptualization, preparation, and revision. VHIO would like to acknowledge the Cellex Foundation for providing research facilities and equipment and the CERCA Programme from the Generalitat de Catalunya for their support of this research. The authors from VHIO acknowledge the State Agency for Research (Agencia Estatal de Investigación) for the financial support as a Center of Excellence Severo Ochoa (CEX2020-001024-S/AEI/10.13039/501100011033). This research is financially supported by the “El paseíco de la mama” Foundation. C. Saura was the recipient of a II FERO-GHD grant from the FERO Foundation (FERO/5086), a Junior Clinical award from the Spanish Association Against Cancer Foundation (FAECC; CLJUN212026ORTI), and a SEOM-Daiichi Sankyo grant for its support on the Breast Cancer Research Projects 2021 (SEOM/FECMA2022) and received funding from the Department of Health (Generalitat de Catalunya SLT008/18/00198) and from the Instituto de Salud Carlos III (ISCIII) and Fondo Europeo de Desarrollo Regional (FEDER), cofunded by the European Union (PI21/01020). C. Ortiz was the recipient of a Junior Clinician award from the FAECC (CLJUN212026ORTI) and a SEOM-Daiichi Sankyo grant for its support on the Breast Cancer Research Projects 2021 (SEOM/FECMA2022), and received funding from the Department of Health (Generalitat de Catalunya SLT008/18/00198). N. Bayó-Puxan received funding from the Department of Health (Generalitat de Catalunya SLT008/18/00205), MCIN/AEI/10.13039/501100011033 (GPE2022-001029) and MCIN/AEI/10.130.39/501100011033, and the European Union “Next GenerationEU/PRTR” (ECT2020-000827). J.M. Miquel received funding from the Department of Health (Generalitat de Catalunya SLT008/18/00205), MCIN/AEI/10.130.39/501100011033, and the European Union “Next GenerationEU/PRTR” (ECT2020-000827). J. Arribas is funded by the Breast Cancer Research Foundation (BCRF-23-008), Instituto de Salud Carlos III (project reference numbers AC15/00062, CB16/12/00449, and PI22/00001), and the European Commission under the framework of the ERA-NET TRANSCAN-2 initiative cofinanced by FEDER and Asociación Española Contra el Cáncer. A. Vivancos was the recipient of a project award from the FAECC (AVP/18/AECC/3219) and received funding from the Advanced Molecular Diagnostic (DIAMAV) program from the FERO Foundation (8361) and from ISDIN for supporting the development of liquid biopsy applications at the Cancer Genomics Lab (1848). M. Sansó was the recipient of a II FERO-GHD grant from the FERO Foundation (FERO/5086) and an investigator award from the FAECC (INVES19056SANS), and received funding from the Health Research Institute of the Balearic Islands (IdISBa), the RADIX-Janssen program (RADIX/JANSSEN21/01), and the Miguel Servet Program funded by the ISCIII (CP22/00131)

Adipose-derived mesenchymal stromal cells for the treatment of patients with severe SARS-CoV-2 pneumonia requiring mechanical ventilation. A proof of concept study

Background: Identification of effective treatments in severe cases of COVID-19 requiring mechanical ventilation represents an unmet medical need. Our aim was to determine whether the administration of adipose-tissue derived mesenchymal stromal cells (AT-MSC) is safe and potentially useful in these patients. Methods: Thirteen COVID-19 adult patients under invasive mechanical ventilation who had received previous antiviral and/or anti-inflammatory treatments (including steroids, lopinavir/ritonavir, hydroxychloroquine and/or tocilizumab, among others) were treated with allogeneic AT-MSC. Ten patients received two doses, with the second dose administered a median of 3 days (interquartile range-IQR- 1 day) after the first one. Two patients received a single dose and another patient received 3 doses. Median number of cells per dose was 0.98 × 106 (IQR 0.50 × 106) AT-MSC/kg of recipient's body weight. Potential adverse effects related to cell infusion and clinical outcome were assessed. Additional parameters analyzed included changes in imaging, analytical and inflammatory parameters. Findings: First dose of AT-MSC was administered at a median of 7 days (IQR 12 days) after mechanical ventilation. No adverse events were related to cell therapy. With a median follow-up of 16 days (IQR 9 days) after the first dose, clinical improvement was observed in nine patients (70%). Seven patients were extubated and discharged from ICU while four patients remained intubated (two with an improvement in their ventilatory and radiological parameters and two in stable condition). Two patients died (one due to massive gastrointestinal bleeding unrelated to MSC therapy). Treatment with AT-MSC was followed by a decrease in inflammatory parameters (reduction in C-reactive protein, IL-6, ferritin, LDH and d-dimer) as well as an increase in lymphocytes, particularly in those patients with clinical improvement. Interpretation: Treatment with intravenous administration of AT-MSC in 13 severe COVID-19 pneumonia under mechanical ventilation in a small case series did not induce significant adverse events and was followed by clinical and biological improvement in most subjects. Funding: None.We would like to acknowledge the Instituto de Salud Carlos III (ISCIII) through the project “RD16/0011: Red de Terapia Celular”, from the sub-program RETICS, integrated in the “Plan Estatal de I+D+I 2013-2016” and co-financed by the European Regional Development Fund “A way to make Europe”, groups RD16/0011/0001, -/0002, -/005, -/0013, -/0015, -/0029), the Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, Spain and AvanCell-CM (Red de Investigación de Terapia Celular de la Comunidad de Madrid, Spain), for supporting some personnel and networking activities