SingleNucleotide Polymorphisms as Biomarkers of Mepolizumab and Benralizumab Treatment Response in Severe Eosinophilic Asthma.

The most promising treatment options for severe uncontrolled asthma (SUA) have emerged in recent years with the development of monoclonal antibodies for blocking selective targets responsible for the underlying inflammation, such as mepolizumab and benralizumab. However, there is variability in treatment response that is not fully controlled. The variability of the response to mepolizumab and benralizumab could be influenced by single-nucleotide polymorphisms (SNPs), and it would be useful to detect these and use them as predictive biomarkers of response. We conducted a retrospective observational cohort study of 72 Caucasian patients recruited from a tertiary hospital with severe uncontrolled eosinophilic asthma treated with mepolizumab and benralizumab. Polymorphisms in the IL5 (rs4143832, rs17690122), RAD50 (rs11739623, rs4705959), IL1RL1 (rs1420101, rs17026974, rs1921622), GATA2 (rs4857855), IKZF2 (rs12619285), FCGR2A (rs1801274), FCGR2B (rs3219018, rs1050501), FCGR3A (rs10127939, rs396991), FCER1A (rs2251746, rs2427837), FCER1B (rs1441586, rs573790, rs569108), and ZNF415 (rs1054485) genes were analyzed by real-time polymerase chain reaction (PCR) using Taqman probes. The response was analyzed after 12 months of treatment. In patients under mepolizumab treatment, a treatment response defined as a reduction in exacerbations was associated with ZNF415 rs1054485-T (p = 0.042; OR = 5.33; 95% CI = 1.06-30.02), treatment response defined as a reduction in oral corticosteroids use was associated with the number of exacerbations in the previous year (p = 0.029; OR = 3.89; 95% CI = 1.24-14.92), and treatment response defined as improvement in lung function was associated with the age at the beginning of biological therapy (p = 0.002; OR = 1.10; 95% CI = 1.04-1.18), FCER1B rs569108-AA (p < 0.001; OR = 171.06; 95% CI = 12.94-6264.11), and FCER1A rs2427837-A (p = 0.021; OR = 8.61; 95% CI = 1.71-76.62). On the other hand, in patients under benralizumab treatment, treatment response, defined as a reduction in exacerbations, was associated with ZNF415 rs1054485-T (p = 0.073; OR = 1.3 × 108; 95% CI = 1.8 × 10-19-NA), FCER1B rs569108-AA (p = 0.050; OR = 11.51; 95% CI = 1.19-269.78), allergies (p = 0.045; OR = 4.02; 95% CI = 1.05-16.74), and sex (p = 0.028; OR = 4.78; 95% CI = 1.22-20.63); and treatment response defined as improvement in lung function was associated with polyposis (p = 0.027; OR = 9.16; 95% CI = 1.58-91.4), IKZF2 rs12619285-AA (p = 0.019; OR = 9.1; 95% CI = 1.7-75.78), IL5 rs4143832-T (p = 0.017; OR = 11.1; 95% CI = 1.9-112.17), and FCER1B rs1441586-C (p = 0.045; OR = 7.81; 95% CI = 1.16-73.45). The results of this study show the potential influence of the studied polymorphisms on the response to mepolizumab and benralizumab and the clinical benefit that could be obtained by defining predictive biomarkers of treatment response.

Evolution of Acute Respiratory Distress Syndrome in Emergency and Critical Care: Therapeutic Management before and during the Pandemic Situation.

Background and Objectives: Acute respiratory distress syndrome is a life-threatening lung condition that prevents enough oxygen from getting to the lungs and blood. The causes can be varied, although since the COVID-19 pandemic began there have been many cases related to this virus. The management and evolution of ARDS in emergency situations in the last 5 years was analyzed. Materials and Methods: A systematic review was carried out in the PubMed and Scopus databases. Using the descriptors Medical Subject Headings (MeSH), the search equation was: "Emergency health service AND acute respiratory distress syndrome". The search was conducted in December 2021. Quantitative primary studies on the care of patients with ARDS in an emergency setting published in the last 5 years were included. Results: In the initial management, adherence to standard treatment with continuous positive airway pressure (CPAP) is recommended. The use of extracorporeal membrane reduces the intensity of mechanical ventilation or as rescue therapy in acute respiratory distress syndrome (ARDS). The prone position in both intubated and non-intubated patients with severe ARDS is associated with a better survival of these patients, therefore, it is very useful in these moments of pandemic crisis. Lack of resources forces triage decisions about which patients are most likely to survive to start mechanical ventilation and this reflects the realities of intensive care and emergency care in a resource-limited setting. Conclusions: adequate prehospital management of ARDS and in emergency situations can improve the prognosis of patients. The therapeutic options in atypical ARDS due to COVID-19 do not seem to vary substantially from conventional ARDS.

IBD and Motherhood: A Journey through Conception, Pregnancy and Beyond.

Inflammatory Bowel Disease (IBD) presents distinct challenges during pregnancy due to its influence on maternal health and pregnancy outcomes. This literature review aims to dissect the existing scientific evidence on pregnancy in women with IBD and provide evidence-based recommendations for clinical management. A comprehensive search was conducted across scientific databases, selecting clinical studies, systematic reviews, and other pertinent resources. Numerous studies have underscored an increased risk of complications during pregnancy for women with IBD, including preterm birth, low birth weight, neonates small for gestational age, and congenital malformations. Nevertheless, it's evident that proactive disease management before and throughout pregnancy can mitigate these risks. Continuation of IBD treatment during pregnancy and breastfeeding is deemed safe with agents like thiopurines, anti-TNF, vedolizumab, or ustekinumab. However, there's a call for caution when combining treatments due to the heightened risk of severe infections in the first year of life. For small molecules, their use is advised against in both scenarios. Effective disease management, minimizing disease activity, and interdisciplinary care are pivotal in attending to women with IBD. The emphasis is placed on the continual assessment of maternal and infant outcomes and an expressed need for further research to enhance the understanding of the ties between IBD and adverse pregnancy outcomes.

Prevalence and Risk Factors of Respiratory Syncytial Virus in Children under 5 Years of Age in the WHO European Region: A Systematic Review and Meta-Analysis.

A respiratory syncytial virus (RSV) is the major cause of respiratory tract infection in children under 5 years. However, RSV infection in the European Region of the World Health Organization has not been systematically reviewed. The aim was to determine the prevalence and factors associated with RSV in children under 5 years of age in European regions. A systematic review and meta-analysis was performed. CINAHL, Medline, LILACS, ProQuest, SciELO, and Scopus databases were consulted for studies published in the last 5 years, following Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. The search equation was "respiratory syncytial virus AND (newborn OR infant OR child) AND (prevalence OR risk factors)". Studies reporting the prevalence of RSV were eligible for inclusion in the meta-analysis. A total of 20 articles were included. The meta-analytic prevalence estimation of RSV, with a sample of n = 16,115 children, was 46% (95% CI 34-59%). The main risk factors were age, male gender, winter season, and environmental factors such as cold temperatures, higher relative humidity, high concentrations of benzene, exposure to tobacco, and living in urban areas. Robust age-specific estimates of RSV infection in healthy children should be promoted in order to determine the optimal age for immunization. In addition, it is necessary to analyse in greater depth the potentially predictive factors of RSV infection, to be included in prevention strategies.

Risk Factors for Short-Term Lung Cancer Survival.

BACKGROUND: Lung cancer is typically diagnosed in an advanced phase of its natural history. Explanatory models based on epidemiological and clinical variables provide an approximation of patient survival less than one year using information extracted from the case history only, whereas models involving therapeutic variables must confirm that any treatment applied is worse than surgery in survival terms. Models for classifying less than one year survival for patients diagnosed with lung cancer which are able to identify risk factors and quantify their effect for prognosis are analyzed. METHOD: Two stepwise binary logistic regression models, based on a retrospective study of 521 cases of patients diagnosed with lung cancer in the Interventional Pneumology Unit at the Hospital "Virgen de las Nieves", Granada, Spain. RESULTS: The first model included variables age, history of pulmonary neoplasm, tumor location, dyspnea, dysphonia, and chest pain. The independent risk factors age greater than 70 years, a peripheral location, dyspnea and dysphonia were significant. For the second model, treatments were also significant. CONCLUSIONS: Age, history of pulmonary neoplasm, tumor location, dyspnea, dysphonia, and chest pain are predictors for survival in patients diagnosed with lung cancer at the time of diagnosis. The treatment applied is significant for classifying less than one year survival time which confirms that any treatment is markedly inferior to surgery in terms of survival. This allows to consider applications of more or less aggressive treatments, anticipation of palliative cares or comfort measures, inclusion in clinical trials, etc.

Small cell lung cancer: Recent changes in clinical presentation and prognosis.

BACKGROUND: Small cell lung cancer (SCLC) is a leading cause of death all over the world. Diagnostic and therapeutic arsenals have improved in recent years, but we are unsure as to whether these advances have been transferred to clinical practice. The aim of this study was to evaluate differences in SCLC diagnostic processes and short-term survival rates between two recent cohorts. METHODS: A prospective, observational study was conducted with patients diagnosed with SCLC (either at extensive or limited stages) in the 2011-2016 period. Patients were divided into two cohorts (2011-2013 and 2014-2016) and followed up for 1 year after diagnosis. RESULTS: Around 713 patients with lung cancer were selected, 134 of whom had SCLC (74 patients in the 2011-2013 cohort and 60 in the 2014-2016 cohort). We observed a chronological increase in the use of endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) and positron emission tomography-computed tomography (PET-CT) between the cohorts. Overall, short-term survival was similar between the two groups and improved survival was associated with age and limited stage. CONCLUSIONS: Changes in diagnostic process in SCLC have been observed towards a more precise stadification. Although short-term survival has not changed for SCLC, it is unclear that the real benefit of PET-CT and EBUS-TBNA is far from correct disease staging.

Changes in non-small cell lung cancer diagnosis, molecular testing and prognosis 2011-2016.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a leading cause of death all over the world. Diagnostic and therapeutic arsenals have improved in recent years, but we are unsure as to whether these advances have been transferred to clinical practice. The aim of this study was to evaluate differences in NSCLC diagnostic processes and short-term survival rates between two recent cohorts. METHODS: A prospective, observational study was conducted with patients diagnosed with NSCLC in the period of 2011-2016. Patients were divided into two cohorts (2011-2013 and 2014-2016), and monitored for up to 1 year after diagnosis. RESULTS: A total of 713 patients with lung cancer were selected, 500 of whom had NSCLC (222 patients in the 2011-2013 cohort, and 278 in the 2014-2016 cohort). We observed a chronological increase in the use of endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) and ultrasound-guided transthoracic puncture (US-TTP) between the cohorts. Overall short-term survival was similar between the two groups, both for locally and for advanced disease. Treatment with tyrosine kinase inhibitors (TKI) was the only therapeutic factor associated with an improved likelihood of survival. CONCLUSIONS: Changes in diagnostic process in NSCLC have been observed towards a more precise stratification. Although short-term survival has not changed for advanced NSCLC, some of the newer therapeutic options are associated with increased survival in real-world scenarios.

[Epidemiological Evolution of Lung Cancer in the South of Spain from 1990 to 2010].

BACKGROUND: Changes in lung cancer has been characterized by the increase of cases among women and the increase in adenocarcinomas among other histological subtypes. METHODS: Descriptive analysis of cases diagnosed with lung cancer in Hospital Virgen de las Nieves (Spain) from 1990 to 2010, based on five variables (age, sex, smoking, histology and pathological anatomy). The study establishes associations between these variables and compares the results with the literature. RESULTS: 2,026 patients were diagnosed with lung cancer in this period; 1,838 were males (90.7%) and 188 women (9.3%); 1,892 patients (93.4%) were smokers or ex-smokers and 134 (6.6%) had never smoked; the most frequent non-small cell histology types were squamous cell carcinoma and adenocarcinoma and it was the most frequent neoplasia in women and were associated with a lower tobacco consumption. CONCLUSIONS: The large majority of lung cancer cases is associated with a history of smoking tobacco and there are histopathological differences according to gender and cumulative tobacco smoke load.