The IL1B-511 Polymorphism (rs16944 AA Genotype) Is Increased in Aspirin-Exacerbated Respiratory Disease in Mexican Population

Aspirin exacerbated respiratory disease (AERD) is characterized by chronic hyperplastic rhinosinusitis, nasal polyposis, asthma, and aspirin sensitivity. The mechanisms which produce these manifestations of intolerance are not fully defined, current research focuses on cyclooxygenase 1 (COX-1) inhibition, metabolism of arachidonic acid, and the COX pathway to the lipoxygenase (LO) route, inducing increased synthesis of leukotrienes (LT). The biological plausibility of this model has led to the search for polymorphisms in genes responsible for proinflammatory cytokines synthesis, such as IL1B and IL8. We performed a genetic association study between IL8-251 (rs4073) and IL1B-511 (rs16944) polymorphisms in AERD, aspirin-tolerant asthma (ATA), and healthy control subjects. Using allelic discrimination by real-time PCR, we found statistically nonsignificant associations between AERD, ATA, and healthy control subjects for the GG and GA genotypes of IL1B (rs16944). Interestingly, the AA genotype showed an increased frequency in the AERD patients versus the ATA group (GF = 0.19 versus 0.07, p = 0.018, OR 2.98, and 95% CI 1.17–7.82). This is the first observation that IL1B polymorphisms are involved in AERD. Thus, future studies must investigate whether interleukin-1β is released in the airways of AERD patients and whether it relates to genetic polymorphisms in the IL1B gene

Evaluation of two treatment strategies for the prevention of preterm birth in women identified as at risk by ultrasound (PESAPRO Trial): Study protocol for a randomized controlled trial

Background: Premature birth is considered one of the main problems in modern Obstetrics. It causes more than 50 % of neonatal mortality; it is responsible for a large proportion of infant morbidity and incurs very high economic costs. Cervical length, which can be accurately measured by ultrasound, has an inverse relationship with the risk of preterm birth. As a result, having an effective intervention for asymptomatic patients with short cervix could reduce the prematurity. Although recently published data demonstrates the effectiveness of vaginal progesterone and cervical pessary, these treatments have never been compared to one another. Methods/Design: The PESAPRO study is a noncommercial, multicenter, open-label, randomized clinical trial (RCT) in pregnant women with a short cervix as identified by transvaginal ultrasonography at 19 to 22 weeks of gestation. Patients are randomized (1:1) to either daily vaginal progesterone or cervical pessary until the 37th week of gestation or delivery; whichever comes first. During the trial, women visit every 4 weeks for routine questions and tests. The primary outcome is the proportion of spontaneous preterm deliveries before 34 weeks of gestation. A sample size of 254 pregnant women will be included at 29 participating hospitals in order to demonstrate noninferiority of placing a pessary versus vaginal progesterone. The first patient was randomized in August 2012, and recruitment of study subjects will continue until the end of December 2015. Discussion: This trial assesses the comparative efficacy and safety between two accepted treatments, cervical pessary versus vaginal progesterone, and it will provide evidence in order to establish clinical recommendationsThe study has been funded by two national grants from the Spanish Ministry of Health and ISCIII

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Curso de especialidad en la carrera de Administración y Negocios Internacionales, de carácter teórico-práctico, dirigido a los estudiantes del 1er ciclo, que aborda los principios básicos de la teoría administrativa global y su evolución, naturaleza y funcionamiento, desde una perspectiva del libre comercio en el contexto de la globalización del Siglo XXI. Los contenidos teóricos, además, están asociados al estudio de factores internos y externos para la definición de la estrategia de negocios, midiendo y analizando variables vinculadas a la cultura, las relaciones laborales, los entornos empresariales, el mercado y las actividades de los competidores nacionales e internacionales. 1La globalización de los negocios significa que los decisores y el personal gerencial administrativo de una organización trabajen e interactúen con miembros de otras culturas, valorando los distintos entornos y siendo capaces de gestionarlo de manera eficiente para lograr los resultados de una organización empresarial

All Roads Lead to Rome: Results of Non-Invasive Respiratory Therapies Applied in a Tertiary-Care Hospital Without an Intermediate Care Unit During the COVID-19 Pandemic

Introducción. Las terapias respiratorias no invasivas (TRNI) fueron ampliamente utilizadas en la primera ola de la pandemia de COVID-19, en escenarios distintos según los medios disponibles. El objetivo fue presentar la supervivencia a 90 días y los factores asociados a esta de los pacientes tratados con TRNI en un centro de tercer nivel sin Unidad de Cuidados Respiratorios Intermedios. Como objetivo secundario comparar los resultados obtenidos de las distintas terapias. Métodos. Estudio observacional de pacientes tratados con TRNI fuera de un ambiente de Cuidados Intensivos o Unidad de Cuidados Respiratorios Intermedios, diagnosticados de COVID-19 y con síndrome de distrés respiratorio agudo por criterios radiológicos y de ratio SpO2/FiO2. Se desarrolló un modelo multivariante de regresión logística para determinar las variables independientemente asociadas, y se compararon los resultados de la terapia de alto flujo con cánula nasal y la presión positiva continua en la vía aérea. Resultados. Se trataron 107 pacientes y sobrevivieron 85 (79,4%) a los 90 días. Antes de iniciar la TRNI el ratio medio de SpO2/FiO2 fue de 119,8±59,4. Un mayor score de SOFA se asoció significativamente a la mortalidad (OR 2,09; IC95% 1,34 – 3,27), mientras que la autopronación fue un factor protector (OR 0,23; IC95% 0,06 – 0,91). La terapia de alto flujo con cánula nasal fue utilizada en 63 sujetos (58,9%), y la presión positiva continua en la vía aérea en 41 (38,3%). No se encontraron diferencias entre ellas. Conclusión. Aproximadamente cuatro de cada cinco pacientes tratados con TRNI sobrevivieron a los 90 días, y no se encontraron diferencias significativas entre la terapia de alto flujo con cánula nasal y la presión positiva continua en la vía aérea.S

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Biologic Therapies for Asthma and Allergic Disease: Past, Present, and Future

The discovery of the mechanism underlying allergic disease, mouse models of asthma, and bronchoscopy studies provided initial insights into the role of Th2-type cytokines, including interlukin (IL)-4, IL-5 and IL-13, which became the target of monoclonal antibody therapy. Omalizumab, Benralizumab, Mepolizumab, Reslizumab, and Tezepelumab have been approved. These biologicals have been shown to be good alternative therapies to corticosteroids, particularly in severe asthma management, where they can improve the quality of life of many patients. Given the success in asthma, these drugs have been used in other diseases with type 2 inflammation, including chronic rhinosinusitis with nasal polyps (CRSwNP), atopic dermatitis, and chronic urticaria. Like the Th2-type cytokines, chemokines have also been the target of novel monoclonal therapies. However, they have not proved successful to date. In this review, targeted therapy is addressed from its inception to future applications in allergic diseases

Galectin-10 Is Released in the Nasal Lavage Fluid of Patients with Aspirin-Sensitive Respiratory Disease

The aim of this work was to determine the presence of galectin-10 in nasal lavage fluid (NLF) of patients with aspirin-sensitive respiratory disease (ASRD) before and after challenge with L-ASA (aspirin) by ELISA. Fifteen ASRD patients, ten aspirin-tolerant asthmatics (ATA), and fifteen healthy controls (HC) were studied. The baseline presence of Galectin-10 in PBMC was determined using real time PCR. Galectin-10 was evaluated in tissue of nasal polyps by western blot. Our results showed a lower expression in PBMC of ASRD patients than in ATA and healthy controls. However, a higher concentration of galectin-10 in NLF was found in ASRD patients before and after L-ASA challenge; western blot confirmed a high expression of galectin-10 in tissue from nasal polyps obtained from ASRD patients. Our results suggest a probable role of galectin-10 in the inflammatory response observed in ASRD patients; however, confirmatory studies are needed