Influence of Genetics on the Response to Omalizumab in Patients with Severe Uncontrolled Asthma with an Allergic Phenotype.

Omalizumab is a monoclonal antibody indicated for the treatment of severe uncontrolled asthma with an allergic phenotype. Its effectiveness could be influenced by clinical variables and single nucleotide polymorphisms (SNPs) in one or more of the genes involved in the mechanism of action and process of response to omalizumab, and these could be used as predictive biomarkers of response. We conducted an observational retrospective cohort study that included patients with severe uncontrolled allergic asthma treated with omalizumab in a tertiary hospital. Satisfactory response after 12 months of treatment was defined as (1) Reduction ≥ 50% of exacerbations or no exacerbations, (2) Improvement of lung function ≥ 10% FEV1, and (3) Reduction ≥ 50% of OCS courses or no OCS. Polymorphisms in the FCER1A (rs2251746, rs2427837), FCER1B (rs1441586, rs573790, rs1054485, rs569108), C3 (rs2230199), FCGR2A (rs1801274), FCGR2B (rs3219018, rs1050501), FCGR3A (rs10127939, rs396991), IL1RL1 (rs1420101, rs17026974, rs1921622), and GATA2 (rs4857855) genes were analyzed by real-time polymerase chain reaction (PCR) using TaqMan probes. A total of 110 patients under treatment with omalizumab were recruited. After 12 months of treatment, the variables associated with a reduction in exacerbations were the absence of polyposis (odds ratio [OR] = 4.22; 95% confidence interval [CI] = 0.95-19.63), IL1RL1 rs17026974-AG (OR = 19.07; 95% CI = 1.27-547), and IL1RL1 rs17026974-GG (OR = 16.76; 95% CI = 1.22-438.76). Reduction in oral corticosteroids (OCS) was associated with age of starting omalizumab treatment (OR = 0.95; 95% CI = 0.91-0.99) and blood eosinophil levels > 300 cells/µL (OR = 2.93; 95% CI = 1.01-9.29). Improved lung function showed a relationship to the absence of chronic obstructive pulmonary disease (COPD) (OR = 12.16; 95% CI = 2.45-79.49), FCGR2B rs3219018-C (OR = 8.6; 95% CI = 1.12-117.15), GATA2 rs4857855-T (OR = 15.98; 95% CI = 1.52-519.57) and FCGR2A rs1801274-G (OR = 13.75; 95% CI = 2.14-142.68; AG vs. AA and OR = 7.46; 95% CI = 0.94-89.12; GG vs. AA). Meeting one response criterion was related to FCER1A rs2251746-TT (OR = 24; 95% CI = 0.77-804.57), meeting two to age of asthma diagnosis (OR = 0.93; 95% CI = 0.88-0.99), and meeting all three to body mass index (BMI) < 25 (OR = 14.23; 95% CI = 3.31-100.77) and C3 rs2230199-C (OR = 3; 95% CI = 1.01-9.92). The results of this study show the possible influence of the polymorphisms studied on the response to omalizumab and the clinical benefit that could be obtained by defining predictive biomarkers of treatment response.

Validation of RayStation Monte Carlo dose calculation algorithm for multiple LINACs.

PURPOSE: A photon Monte Carlo (MC) model was commissioned for flattened (FF) and flattening filter free (FFF) 6 MV beam energy. The accuracy of this model, as a single model to be used for three beam matched LINACs, was evaluated. METHODS: Multiple models were created in RayStation v.10A for three linacs equipped with Elekta "Agility" collimator. A clinically commissioned collapsed cone (CC) algorithm (GoldCC), a MC model automatically created from the CC algorithm without further optimization (CCtoMC) and an optimized MC model (GoldMC) were compared with measurements. The validation of the model was performed by following the recommendations of IAEA TRS 430 and comprised of basic validation in a water tank, validation in a heterogeneous phantom and validation of complex IMRT/VMAT paradigms using gamma analysis of calculated and measured dose maps in a 2D-Array. RESULTS: Dose calculation with the GoldMC model resulted in a confidence level of 3% for point measurements in water tank and heterogeneous phantom for measurements performed in all three linacs. The same confidence level resulted for GoldCC model. Dose maps presented an agreement for all models on par to each other with γ criteria 2%/2mm. CONCLUSIONS: The GoldMC model showed a good agreement with measured data and is determined to be accurate for clinical use for all three linacs in this study.

Association between Single Nucleotide Polymorphisms Related to Vitamin D Metabolism and the Risk of Developing Asthma.

Asthma is a chronic non-communicable disease that affects all age groups. The main challenge this condition poses is its heterogeneity. The role of vitamin D in asthma has aroused great interest, correlating low vitamin D levels and polymorphisms in the genes involved in its metabolic pathway with the risk of asthma. The aim of this study was to evaluate the influence of 13 single nucleotide polymorphisms (SNPs) related to the vitamin D metabolism on the susceptibility to asthma. An observational case-control study was performed, including 221 patients with asthma and 442 controls of Caucasian origin from southern Spain. The SNPs CYP24A1 (rs6068816, rs4809957), CYP27B1 (rs10877012, rs4646536, rs703842, rs3782130), GC (rs7041), CYP2R1 (rs10741657) and VDR (ApaI, BsmI, FokI, Cdx2, TaqI) were analyzed by real-time PCR, using TaqMan probes. The logistic regression model adjusted for body mass index revealed that in the genotype model, carriers of the Cdx2 rs11568820-AA genotype were associated with a higher risk of developing asthma (p = 0.005; OR = 2.73; 95% CI = 1.36-5.67; AA vs. GG). This association was maintained in the recessive model (p = 0.004). The haplotype analysis revealed an association between the ACTATGG haplotype and higher risk of asthma for the rs1544410, rs7975232, rs731236, rs4646536, rs703842, rs3782130 and rs10877012 genetic polymorphisms (p = 0.039). The other SNPs showed no effect on risk of developing asthma. The Cdx2 polymorphism was significantly associated with the susceptibility of asthma and could substantially act as a predictive biomarker of the disease.

Impact of Omalizumab in Patients with Severe Uncontrolled Asthma and Possible Predictive Biomarkers of Response: A Real-Life Study.

Most patients with asthma can control their symptoms with a basic standard of medical care and with maintenance and rescue medication. However, between 5% and 10% of asthmatics worldwide do not achieve control of their symptoms and have recurrent exacerbations and respiratory difficulties. The objective of the study was the real-life evaluation of the clinical improvement of patients with severe eosinophilic asthma treated with omalizumab, together with the search for biomarkers associated with the response. An observational retrospective cohort study was conducted that included patients with severe uncontrolled allergic asthma being treated with omalizumab. Three types of response were evaluated: lower use of oral corticosteroids, improvement in lung function, and reduction in exacerbations. A total of 110 patients under treatment with omalizumab were included, with a mean age of 48 ± 16 years. After 12 months had elapsed, significant reductions were found in the number of exacerbations, use of oral cortico-steroids and doses of inhaled corticosteroids (p < 0.001). Lung function and asthma control improved significantly (p < 0.001; p = 0.004) and eosinophil levels were significantly reduced (p = 0.004). Low scores in the Asthma Control Test were associated with the oral corticosteroid-saving effect; lower previous FEV1 levels and absence of chronic obstructive pulmonary disease (COPD) were related to improvement in lung function, and prior FEV1 values higher than 80% and absence of gastroesophageal reflux disease (GERD) with a reduction in exacerbations. The results of this study confirm the clinical benefit obtained after the introduction of omalizumab and the possible predictive biomarkers of response to the treatment.

Impact of Anti-IL5 Therapies on Patients with Severe Uncontrolled Asthma and Possible Predictive Biomarkers of Response: A Real-Life Study.

Severe Uncontrolled Asthma (SUA) counts for more than 25% of cases of severe asthma. The main factors that impair the quality of life of these patients are high doses of oral corticosteroids, the presence of exacerbations, and reduced lung function. The objective of this study was to evaluate, in real life, the clinical improvement of patients with SUA treated with anti-interleukin 5 (IL5) therapies: mepolizumab and benralizumab, together with the search for biomarkers associated with the response. We conducted a retrospective observational cohort study that included patients with severe uncontrolled eosinophilic asthma in a tertiary hospital receiving biological therapies. Three types of response were evaluated: improvement in lung function, reduction in exacerbations, and decrease in the use of oral corticosteroids. After 12 months of treatment, significant reductions were found in the number of exacerbations, the use of oral corticosteroids, and blood eosinophil levels for both biological therapies (p < 0.001). Lung function improved, achieving a significant improvement in %FEV1 (p < 0.001), as well as asthma control, with a significant increase in asthma control test (ACT) scores in both therapies. The markers associated with the corticosteroid-saving effect were the low doses of oral corticosteroids and absence of exacerbations for mepolizumab, and higher blood eosinophilia, absence of chronic obstructive pulmonary disease (COPD), and reduction in oral corticosteroid cycles for benralizumab. The greatest improvement in lung function in both therapies was linked to lower previous FEV1 levels and absence of other respiratory diseases. The reduction in exacerbations was associated with absence of exacerbations the previous year for mepolizumab and never smokers for benralizumab. The results of this real-life study confirm the clinical benefit obtained after the introduction of an anti-IL5 biological therapy and the possible predictive biomarkers of response to treatment.

Public perception of healthcare system response to COVID-19: Findings from a web based observational study in Villavicencio, Colombia.

This study explores the community perceptions of COVID-19 and the healthcare system's response to it.: A web-based descriptive observational study was conducted on the general population during the third quarter of 2020 through the application of a survey via social media. Of the sample, 55% have minimal connection with prevention programs, while 66.3% received little or no information about COVID-19, and 69.62% were considered at risk of getting sick from COVID-19. Further, 73.14% were afraid to go to healthcare centers fearing the risk of becoming infected by COVID-19. The low-income population is at greater risk (OR 4.32), as well as those who have not been informed by their insurer of the risks of COVID-19 (OR 2.18). There is a need to strengthen the healthcare system and the quality and design of effective self-care educational interventions during the pandemic.

Experimental evidences support the existence of an aggregation/disaggregation step in the Turkevich synthesis of gold nanoparticles.

Turkevich method is one of the most employed techniques to synthesize gold nanoparticles. Despite its simplicity, the mechanism has been an issue of debate over the past years. The general belief is that particles are formed by a classical nucleation and growth theory, originally described by LaMer's model. In the present work, we provide new experimental evidences that supports either LaMer's theory and their detractors. In the former model, it is proposed that particles are generated by a burst nucleation form the initial 'seeds', from which their growth in a second and quasi-independent step. Instead, our experiments (DLS, UV/VIS and TEM measurements) support the idea that nanoparticles 'seeds' tend to form large intermediate clusters at the beginning of the synthesis, that afterwards disassemble to yield the final nanoparticles. However, unlike other reports, we propose that during the cluster formation the particles do not coalesce, instead they come close to each other without losing their identity. As the synthesis continues, these clusters are progressively separated into the final particles. As a consequence, a path to synthesize ultra-narrow size nanoparticles is provided, along with their stability against salt aggregation, and shelf-time. We found that these ultra-homogeneous nanoparticles are stable for several months, making them suitable for many applications in the biomedical and analytical research.

Is asthma in the elderly different? Functional and clinical characteristics of asthma in individuals aged 65 years and older.

BACKGROUND: The prevalence of chronic diseases in the elderly (> 65 years), including asthma, is growing, yet information available on asthma in this population is scarce.Our objective is to determine the differential clinical and functional characteristics of the population > 65 years old with asthma included in the Integrated Research Programs of Asthma Databank of the Spanish Society of Pneumology and Thoracic Surgery (www.bancodatosasma.com). METHODS: Retrospective comparative descriptive study of demographic, clinical and functional variables for 1713 patients with asthma categorized into 3 age groups as follows: adults aged < 65 years (A), younger elderly aged 65-74 years (B) and older elderly aged ≥75 years (C). RESULTS: Predominant features of elderly patients with asthma (N = 471) were the female sex, fewer smokers, greater obesity, poorer lung function, and lower values of nitric oxide in exhaled air (p < 0.01). The most frequently associated comorbidity was gastroesophageal reflux. The highest doses of inhaled corticosteroids were by group A (60.8%). For the sample overall, 23.2% (N = 398) were being treated with omalizumab and 8.2% (N = 140) were corticosteroid-dependent (10.6% in group B). The highest percentage of patients receiving antileukotriene agents was in group B (42.9%). CONCLUSIONS: Asthma in adults aged> 65 is more severe and associated with greater comorbidity, which would indicate the need for a more integrated and multidimensional approach to asthma treatment for these patients.

Modelo predictivo de ansiedad y depresión en pacientes españoles con enfermedad pulmonar obstructiva crónica estable / Predictive Model for Anxiety and Depression in Spanish Patients with Stable Chronic Obstructive Pulmonary Disease

Introducción: La asociación entre la enfermedad pulmonar obstructiva crónica (EPOC) y la ansiedad o la depresión no se conoce adecuadamente, y puede haber diferencias entre distintos países. Investigamos un modelo predictivo para esta asociación en una población española. Pacientes y método: Estudio prospectivo descriptivo transversal incluyendo 204 pacientes con EPOC estable. Se diagnostica la presencia de ansiedad o depresión mediante valoración psiquiátrica, aplicando los criterios diagnósticos de la 10.ª revisión del International Statistical Classification of Diseases and Related Health Problems (ICD-10). Se analizan variables sociodemográficas, clínicas y de función pulmonar. Resultados: Un 36% de pacientes con EPOC estable tienen comorbilidad psiquiátrica, pero en el 76% de los casos se desconocía dicho diagnóstico. Presentan un trastorno de ansiedad pura el 19%, depresión aislada el 9,8% y un trastorno mixto de ansiedad y depresión el 7,3% de los pacientes. En el análisis multivariante las variables predictoras son: edad más joven, mayor nivel de estudios, falta de apoyo domiciliario, mayor índice de BODE y mayor número de agudizaciones. La curva ROC del modelo muestra un AUC de 0,765 (p<0,001). Conclusiones: En la EPOC, una mayoría de pacientes con comorbilidad psiquiátrica no son identificados. Los trastornos de ansiedad son más frecuentes que la depresión, en base a un diagnóstico mediante entrevista estructurada. Los pacientes más jóvenes y con mayor nivel de estudios tienen más riesgo de de padecer ansiedad o depresión. Otros factores predictivos son: un mayor índice BODE, más agudizaciones y la falta de apoyo domiciliario

Introduction: The association between chronic obstructive pulmonary disease (COPD) and anxiety and depression is not yet completely characterized, and differences between countries may exist. We used a predictive model to assess this association in a Spanish population. Patients and method: Prospective transversal descriptive study of 204 patients with stable COPD. Concomitant anxiety or depression were diagnosed by psychiatric assessment, using the diagnostic criteria of the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10). Sociodemographic, clinical and lung function parameters were analyzed. Results: In total, 36% of stable COPD patients had psychiatric comorbidities, but 76% were unaware of their diagnosis. Nineteen percent had a pure anxiety disorder, 9.8% had isolated depression, and 7.3% had a mixed anxiety-depression disorder. Predictive variables in the multivariate analysis were younger age, higher educational level, lack of home support, higher BODE index, and greater number of exacerbations. The ROC curve of the model had an AUC of 0.765 (P<0.001). Conclusions: In COPD, concomitant psychiatric disorders are significantly associated with sociodemographic factors. Anxiety disorders are more common than depression. Patients with more severe COPD, according to BODE, younger patients and those with a higher educational level have a greater risk of being diagnosed with anxiety or depression in a structured psychiatric interview. In our population, most patients with psychiatric comorbidities remain unidentified

Predictive Model for Anxiety and Depression in Spanish Patients with Stable Chronic Obstructive Pulmonary Disease.

INTRODUCTION: The association between chronic obstructive pulmonary disease (COPD) and anxiety and depression is not yet completely characterized, and differences between countries may exist. We used a predictive model to assess this association in a Spanish population. PATIENTS AND METHOD: Prospective transversal descriptive study of 204 patients with stable COPD. Concomitant anxiety or depression were diagnosed by psychiatric assessment, using the diagnostic criteria of the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10). Sociodemographic, clinical and lung function parameters were analyzed. RESULTS: In total, 36% of stable COPD patients had psychiatric comorbidities, but 76% were unaware of their diagnosis. Nineteen percent had a pure anxiety disorder, 9.8% had isolated depression, and 7.3% had a mixed anxiety-depression disorder. Predictive variables in the multivariate analysis were younger age, higher educational level, lack of home support, higher BODE index, and greater number of exacerbations. The ROC curve of the model had an AUC of 0.765 (P<0.001). CONCLUSIONS: In COPD, concomitant psychiatric disorders are significantly associated with sociodemographic factors. Anxiety disorders are more common than depression. Patients with more severe COPD, according to BODE, younger patients and those with a higher educational level have a greater risk of being diagnosed with anxiety or depression in a structured psychiatric interview. In our population, most patients with psychiatric comorbidities remain unidentified.

A reference consensus genetic map for molecular markers and economically important traits in faba bean (Vicia faba L.).

BACKGROUND: Faba bean (Vicia faba L.) is among the earliest domesticated crops from the Near East. Today this legume is a key protein feed and food worldwide and continues to serve an important role in culinary traditions throughout Middle East, Mediterranean region, China and Ethiopia. Adapted to a wide range of soil types, the main faba bean breeding objectives are to improve yield, resistance to biotic and abiotic stresses, seed quality and other agronomic traits. Genomic approaches aimed at enhancing faba bean breeding programs require high-quality genetic linkage maps to facilitate quantitative trait locus analysis and gene tagging for use in a marker-assisted selection. The objective of this study was to construct a reference consensus map in faba bean by joining the information from the most relevant maps reported so far in this crop. RESULTS: A combination of two approaches, increasing the number of anchor loci in diverse mapping populations and joining the corresponding genetic maps, was used to develop a reference consensus map in faba bean. The map was constructed from three main recombinant inbreed populations derived from four parental lines, incorporates 729 markers and is based on 69 common loci. It spans 4,602 cM with a range from 323 to 1041 loci in six main linkage groups or chromosomes, and an average marker density of one locus every 6 cM. Locus order is generally well maintained between the consensus map and the individual maps. CONCLUSION: We have constructed a reliable and fairly dense consensus genetic linkage map that will serve as a basis for genomic approaches in faba bean research and breeding. The core map contains a larger number of markers than any previous individual map, covers existing gaps and achieves a wider coverage of the large faba bean genome as a whole. This tool can be used as a reference resource for studies in different genetic backgrounds, and provides a framework for transferring genetic information when using different marker technologies. Combined with syntenic approaches, the consensus map will increase marker density in selected genomic regions and will be useful for future faba bean molecular breeding applications.

Respuesta nauseosa durante el cepillado en mujeres embarazadas de Bogotá, D.C., Colombia / Nausea during toothbrushing in pregnant women from Bogotá, Colombia

ANTECEDENTES: los síntomas más comunes que trae el embarazo son las naúseas y el vomito, los cuales varían en cuanto a frecuencia, momento de preparación durante la gestación y factores desencadenantes, como la higiene oral, por ejemplo. Ello podría estar relacionado con el deterioro de la salud oral de la mujer en este periodo. PROPÓSITO: identificar y relacionar, en un grupo de mujeres residentes en Bogotá, Colombia, con experiencia previa o actual de embarazo, el porcentaje de aparición de náuseas y vómito, con el cepillado. METODOS: se aplico un cuestionario a 200 mujeres quienes cumplían con las características mencionadas arriba. La encuesta indagaba sobre: estado actual de embarazo, números de embarazos, experiencias de náuseas, momento del día en que fueron más frecuentes las náuseas, sensación de náuseas durante el cepillado, relación de las náuseas con la crema dental, percepción de las náuseas durante el cepillado; de relacionarse con la crema dental, característica de esta que produce las náuseas; cambio de dentífrico, y mejoramiento de los síntomas con esta conducta. Los resultados fueron analizados descriptivamente. HALLAZGOS: se encontró que las mujeres residentes en Bogotá Colombia, encuestadas, con experiencia previa y /o actual de embarazo, habían tenido una alta frecuencia de náuseas y vómito durante ese periodo (64.5/100);esta sintomatología se presentó principalmente en primigrávidas (43.4/100), en horas de la mañana (78.3/100) y en el primer trimestre (55.8/100) o durante todo el embarazo (29.5/100). Así mismo, los procedimientos de higiene oral fueron un factor frecuentemente asociados por ellas a la experiencia de náuseas y vómito durante el embarazo, lo que generó un llamado de atención a los odontólogos por los posibles cambios en estos hábitos y el concomitante desarrollo de enfermedades orales.

Tétanos complicado con hipercalcemia: reporte de un caso / Tetanus complicated with hypercalcemia: a case report

Antecedentes: el tétanos es una enfermedad cada vez menos frecuente y con mejor pronóstico. Sin embargo, la supervivencia de estos pacientes nos enfrenta a nuevas complicaciones. Objetivo: reporta un caso de tétanos que, además de las complicaciones pulmonares esperadas, desarrolló hipercalcemia relacionada con la inmovilización prolongada. Material y métodos: ingresó un paciente con herida punzocortante en el antebrazo; se manejó con sedación, relajación muscular, antibióticos, apoyo ventilatorio mecánico, insulina y nutrición parenteral. Resultados: egresó a los 128 días de hospitalización y permaneció en programa de diálisis peritoneal continua ambulatoria (DPCA) y rehabilitación física. Conclusiones: en la actualidad, los pacientes con diagnóstico de tétanos severo pueden recibir apoyo multisistémico, por lo cual las complicaciones relacionadas tienen una mejor evolución y disminuye la mortalidad. Ahora se deben enfrentar otras complicaciones que repercuten en el pronóstico de estos pacientes