Failing to Make Ends Meet: The Broad Clinical Spectrum of DNA Ligase IV Deficiency. Case Series and Review of the Literature

DNA repair defects are inborn errors of immunity that result in increased apoptosis and oncogenesis. DNA Ligase 4-deficient patients suffer from a wide range of clinical manifestations since early in life, including: microcephaly, dysmorphic facial features, growth failure, developmental delay, mental retardation; hip dysplasia, and other skeletal malformations; as well as a severe combined immunodeficiency, radiosensitivity, and progressive bone marrow failure; or, they may present later in life with hematological neoplasias that respond catastrophically to chemo- and radiotherapy; or, they could be asymptomatic. We describe the clinical, laboratory, and genetic features of five Mexican patients with LIG4 deficiency, together with a review of 36 other patients available in PubMed Medline. Four out of five of our patients are dead from lymphoma or bone marrow failure, with severe infection and massive bleeding; the fifth patient is asymptomatic despite a persistent CD4+ lymphopenia. Most patients reported in the literature are microcephalic females with growth failure, sinopulmonary infections, hypogammaglobulinemia, very low B-cells, and radiosensitivity; while bone marrow failure and malignancy may develop at a later age. Dysmorphic facial features, congenital hip dysplasia, chronic liver disease, gradual pancytopenia, lymphoma or leukemia, thrombocytopenia, and gastrointestinal bleeding have been reported as well. Most mutations are compound heterozygous, and all of them are hypomorphic, with two common truncating mutations accounting for the majority of patients. Stem-cell transplantation after reduced intensity conditioning regimes may be curative

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

MASK (Mobile Airways Sentinel Network), una app móvil con la solución integral de ARIA en países de habla hispana

Aunque existen guías clínicas de alta calidad sobre rinitis alérgica, numerosos pacientes reciben tratamiento deficiente, en parte debido al alto grado de automedicación. MASK (Mobile Airways Sentinel Network) forma parte integral de un proyecto apoyado por la Unión Europea contra las enfermedades crónicas y enfocado al envejecimiento activo y saludable. Constituye la tercera fase de ARIA (Allergic Rhinitis and its Impact on Asthma), en la cual mediante una aplicación móvil en un dispositivo inteligente se intenta guiar al paciente en el control de su multimorbilidad, rinitis o conjuntivitis alérgicas o asma. La aplicación Diario de Alergia por MACVIA-ARIA es gratuita y está disponible para Android e iOS; en ella, los pacientes indican diariamente cuánto les molestan los síntomas a través de cinco pantallas con una escala visual análoga; recientemente se agregaron dos pantallas más (afectación del sueño). La aplicación también permite descargar los datos del “Diario de alergias” en la computadora del médico en el momento de la consulta a través de un código QR. En este artículo reseñamos el primer año de experiencia en España, México y Argentina, que utilizan la versión española.Fil: Larenas Linnemann, Désirée. Fundación Clínica Médica Sur; ArgentinaFil: Mullol, Joaquim. Universitat de Barcelona; EspañaFil: Ivancevich, Juan Carlos. Clínica Santa Isabel; ArgentinaFil: Anto, Josep M. Universitat Pompeu Fabra; EspañaFil: Cardona, Victoria. Hospital Vall d’Hebron; EspañaFil: Dedeu, Toni. European Regional and Local Health Association; BélgicaFil: Rodríguez González, Mónica. Hospital Español; MéxicoFil: Huerta Villalobos, Yunuen Rocío. Instituto Mexicano del Seguro Social; MéxicoFil: Neffen, Hugo. Center of Allergy; ArgentinaFil: Fuentes Pérez, José Miguel. Instituto Mexicano del Seguro Social; MéxicoFil: Rodríguez Zagal, Endira. Instituto Mexicano del Seguro Social; MéxicoFil: Valero, Antonio. Universidad de Barcelona; EspañaFil: Zernotti, Mario Emilio. Universidad Católica de Córdoba. Facultad de Ciencias de la Salud; ArgentinaFil: Bartra, Joan. Hospital Clínic; EspañaFil: Alobid, Isam. Hospital de La Fe; EspañaFil: Castillo Vizuete, José Antonio. Hospital Universitari Quirón; EspañaFil: Dordal, Teresa. Hospital Municipal Badalona; EspañaFil: Hijano, Rafael. Hospital del Mar; EspañaFil: Picado, César. European Federation of Allergy and Respiratory; España Diseases PatientsFil: Sastre, Joaquín. Fundación Jiménez Díaz; EspañaFil: Blua, Ariel Eduardo. Hospital Privado Universitario de Córdoba; ArgentinaFil: Jares, Edgardo. Sociedad Latinoamericana de Alergia; ArgentinaFil: Lavrut, Alberto Jorge. Hospital General de Niños Pedro de Elizalde; ArgentinaFil: Máspero, Jorge. Fundación Centro de Investigación de Enfermedades Alérgicas y Respiratorias; ArgentinaFil: Bedolla Barajas, Martín. Centro Médico Zambrano Hellion; MéxicoFil: Burguete Cabañas, María Teresa. Hospital Ángeles de Puebla; MéxicoFil: García Cobas, Cecilia Yvonne. Hospital Star Médica Aguascalientes; ArgentinaFil: García Cruz, María de la Luz Hortensia. Hospital Ángeles de Puebla; MéxicoFil: Hernández Velázquez, Luiana. 8Universidad Autónoma de Baja California Campus Ensenada; MéxicoFil: Luna Pech, Jorge A. Universidad de Guadalajara; MéxicoFil: Matta, Juan José. Instituto Mexicano del Seguro Social; MéxicoFil: Mogica Martínez, María Dolores. Instituto Mexicano del Seguro Social; MéxicoFil: Rivero Yeverino, Daniela. Universidad Autónoma de Puebla; ArgentinaFil: Ruiz, Lucy Tania. Instituto Mexicano del Seguro Social; MéxicoFil: Del Río Navarro, Blanca E. Hospital Infantil de México; MéxicoFil: Gómez Vera, Javier. Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado; MéxicoFil: Macías Weinmann, Alejandra. Universidad Autónoma de Nuevo León; MéxicoFil: Murray, Ruth. MedScript Ltd; IrlandaFil: Onorato, Gabrielle. MACVIA-France; FranciaFil: Laune, Daniel. Kyomed; FranciaFil: Bedbrook, Anna. MACVIA-France; FranciaFil: Bousquet, Jean. Université Versailles St-Quentin-en-Yvelines; Franci

MASK (Mobile Airways Sentinel Network), una app móvil con la solución integral de ARIA en países de habla hispana

Aunque existen guías clínicas de alta calidad sobre rinitis alérgica, numerosos pacientes reciben tratamiento deficiente, en parte debido al alto grado de automedicación. MASK (Mobile Airways Sentinel Network) forma parte integral de un proyecto apoyado por la Unión Europea contra las enfermedades crónicas y enfocado al envejecimiento activo y saludable. Constituye la tercera fase de ARIA (Allergic Rhinitis and its Impact on Asthma), en la cual mediante una aplicación móvil en un dispositivo inteligente se intenta guiar al paciente en el control de su multimorbilidad, rinitis o conjuntivitis alérgicas o asma. La aplicación Diario de Alergia por MACVIA-ARIA es gratuita y está disponible para Android e iOS; en ella, los pacientes indican diariamente cuánto les molestan los síntomas a través de cinco pantallas con una escala visual análoga; recientemente se agregaron dos pantallas más (afectación del sueño). La aplicación también permite descargar los datos del “Diario de alergias” en la computadora del médico en el momento de la consulta a través de un código QR. En este artículo reseñamos el primer año de experiencia en España, México y Argentina, que utilizan la versión española.Although there are high quality clinical guidelines about allergic rhinitis, many patients receive deficient treatment, partly due to the high level of self-medication. MASK (Mobile Airways Sentinel Network) is an integral part of a project against chronic diseases which it is focused on active and healthy aging and is supported by the European Union. It forms the third phase of ARIA (Allergic Rhinitis and its Impact on Asthma) in which, through a mobile app on a smart device, the purpose is to guide patients in the control of their multimorbidity, allergic rhinitis or conjunctivitis, or asthma. The "Allergy Diary" app by MACVIA-ARIA is free and it is available for Android and iOS; on it, patients indicate how unpleasant the symptoms are on a daily basis through five screens with an analogous visual scale; two more screens were recently added (sleep affectation). With the app, it is also possible to download the information of the "Allergy Diary" on the physician's computer through a QR code at the moment of the medical consultation. In this article, we review the first year of experience in Spain, Mexico and Argentina, where the Spanish version is used

Executive Summary of ARIA 2019: Integrated care pathways for allergic rhinitis in Argentina, Spain and Mexico

El impacto sanitario y económico de las enfermedades alérgicas está aumentando rápidamente y se necesitan cambios en las estrategias para su manejo. Su influencia reduce al menos en un tercio la capacidad de desempeño laboral y escolar. Los ICP (Vías Integradas de Atención) de las enfermedades de las vías respiratorias son planes de atención estructurados y multidisciplinarios, que promueven las recomendaciones de las guías en protocolos locales y su aplicación a la práctica clínica. En este documento se presenta un resumen ejecutivo para Argentina, México y España. Se desarrollan las guías ARIA de próxima generación para el tratamiento farmacológico de la rinitis alérgica (RA) utilizando las pautas basadas en GRADE para RA, probadas con evidencia de la vida real proporcionada por tecnología móvil basada en escalas visuales analógicas. Se concluye que en el tratamiento de la RA, los antihistamínicos anti-H1 son menos efectivos que los corticoides intranasales (CINS), que en la rinitis grave los CINS representan la primera línea de tratamiento, y que la combinación intranasal de CINS + anti-H1 es más eficaz que la monoterapia. Sin embargo, según el estudio MASK observacional en vida real, los pacientes tienen pobre adherencia al tratamiento y frecuentemente se automedican de acuerdo con sus necesidades.The health and economic impact of allergic diseases are increasing rapidly, and changes in management strategies are required. Its influence reduces the capacity of work and school performance by at least a third. The ICPs of the airways (integrated care pathways for respiratory diseases) are structured multidisciplinary healthcare plans, promoting the recommendations of the guidelines in local protocols and their application to clinical practice. This document presents an executive summary for Argentina, Mexico, and Spain. Next-generation ARIA guidelines are being developed for the pharmacological treatment of allergic rhinitis (AR), using the GRADE-based guidelines for AR, tested with real-life evidence provided by mobile technology with visual analogue scales. It is concluded that in the AR treatment, H1-antihistamines are less effective than intranasal corticosteroids (INCS), in severe AR the INCS represent the first line of treatment, and intranasal combination INCS + anti-H1 is more effective than monotherapy. However, according to the MASK real-life observational study, patients have poor adherence to treatment and often self-medicate, according to their needs

Cabbage and fermented vegetables: From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT1R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT1R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.</p