COVID-19 Computed tomography patterns in renal replacement therapy patients / Padrões de tomografia computadorizada da COVID-19 em pacientes em terapia renal substitutiva

ABSTRACT Introduction: Lung diseases are common in patients with end stage kidney disease (ESKD), making differential diagnosis with COVID-19 a challenge. This study describes pulmonary chest tomography (CT) findings in hospitalized ESKD patients on renal replacement therapy (RRT) with clinical suspicion of COVID-19. Methods: ESKD individuals referred to emergency department older than 18 years with clinical suspicion of COVID-19 were recruited. Epidemiological baseline clinical information was extracted from electronic health records. Pulmonary CT was classified as typical, indeterminate, atypical or negative. We then compared the CT findings of positive and negative COVID-19 patients. Results: We recruited 109 patients (62.3% COVID-19-positive) between March and December 2020, mean age 60 ± 12.5 years, 43% female. The most common etiology of ESKD was diabetes. Median time on dialysis was 36 months, interquartile range = 12-84. The most common pulmonary lesion on CT was ground glass opacities. Typical CT pattern was more common in COVID-19 patients (40 (61%) vs 0 (0%) in non-COVID-19 patients, p < 0.001). Sensitivity was 60.61% (40/66) and specificity was 100% (40/40). Positive predictive value and negative predictive value were 100% and 62.3%, respectively. Atypical CT pattern was more frequent in COVID-19-negative patients (9 (14%) vs 24 (56%) in COVID-19-positive, p < 0.001), while the indeterminate pattern was similar in both groups (13 (20%) vs 6 (14%), p = 0.606), and negative pattern was more common in COVID-19-negative patients (4 (6%) vs 12 (28%), p = 0.002). Conclusions: In hospitalized ESKD patients on RRT, atypical chest CT pattern cannot adequately rule out the diagnosis of COVID-19.

RESUMO Introdução: Doenças pulmonares são comuns em pacientes com doença renal em estágio terminal (DRET), dificultando o diagnóstico diferencial com COVID-19. Este estudo descreve achados de tomografia computadorizada de tórax (TC) em pacientes com DRET em terapia renal substitutiva (TRS) hospitalizados com suspeita de COVID-19. Métodos: Indivíduos maiores de 18 anos com DRET, encaminhados ao pronto-socorro com suspeita de COVID-19 foram incluídos. Dados clínicos e epidemiológicos foram extraídos de registros eletrônicos de saúde. A TC foi classificada como típica, indeterminada, atípica, negativa. Comparamos achados tomográficos de pacientes com COVID-19 positivos e negativos. Resultados: Recrutamos 109 pacientes (62,3% COVID-19-positivos) entre março e dezembro de 2020, idade média de 60 ± 12,5 anos, 43% mulheres. A etiologia mais comum da DRET foi diabetes. Tempo médio em diálise foi 36 meses, intervalo interquartil = 12-84. A lesão pulmonar mais comum foi opacidades em vidro fosco. O padrão típico de TC foi mais comum em pacientes com COVID-19 (40 (61%) vs. 0 (0%) em pacientes sem COVID-19, p < 0,001). Sensibilidade 60,61% (40/66), especificidade 100% (40/40). Valores preditivos positivos e negativos foram 100% e 62,3%, respectivamente. Padrão atípico de TC foi mais frequente em pacientes COVID-19-negativos (9 (14%) vs. 24 (56%) em COVID-19-positivos, p < 0,001), enquanto padrão indeterminado foi semelhante em ambos os grupos (13 (20%) vs. 6 (14%), p = 0,606), e padrão negativo foi mais comum em pacientes COVID-19-negativos (4 (6%) vs. 12 (28%), p = 0,002). Conclusões: Em pacientes com DRET em TRS hospitalizados, um padrão atípico de TC de tórax não pode excluir adequadamente o diagnóstico de COVID-19.

COVID-19 Computed tomography patterns in renal replacement therapy patients.

INTRODUCTION: Lung diseases are common in patients with end stage kidney disease (ESKD), making differential diagnosis with COVID-19 a challenge. This study describes pulmonary chest tomography (CT) findings in hospitalized ESKD patients on renal replacement therapy (RRT) with clinical suspicion of COVID-19. METHODS: ESKD individuals referred to emergency department older than 18 years with clinical suspicion of COVID-19 were recruited. Epidemiological baseline clinical information was extracted from electronic health records. Pulmonary CT was classified as typical, indeterminate, atypical or negative. We then compared the CT findings of positive and negative COVID-19 patients. RESULTS: We recruited 109 patients (62.3% COVID-19-positive) between March and December 2020, mean age 60 ± 12.5 years, 43% female. The most common etiology of ESKD was diabetes. Median time on dialysis was 36 months, interquartile range = 12-84. The most common pulmonary lesion on CT was ground glass opacities. Typical CT pattern was more common in COVID-19 patients (40 (61%) vs 0 (0%) in non-COVID-19 patients, p < 0.001). Sensitivity was 60.61% (40/66) and specificity was 100% (40/40). Positive predictive value and negative predictive value were 100% and 62.3%, respectively. Atypical CT pattern was more frequent in COVID-19-negative patients (9 (14%) vs 24 (56%) in COVID-19-positive, p < 0.001), while the indeterminate pattern was similar in both groups (13 (20%) vs 6 (14%), p = 0.606), and negative pattern was more common in COVID-19-negative patients (4 (6%) vs 12 (28%), p = 0.002). CONCLUSIONS: In hospitalized ESKD patients on RRT, atypical chest CT pattern cannot adequately rule out the diagnosis of COVID-19.

People first: a participatory community approach on patient-reported outcomes in tuberculosis.

Patient-reported outcomes (PROs) play a crucial role in understanding the impact of tuberculosis (TB) on both individuals and communities. Despite advances in TB treatment, conventional outcome definitions often overlook essential components of people with TB's experiences, leading to disparities in treatment understanding. The incorporation of PROs in TB scientific research can help bridge the gap between the health system and people's needs and expectations. PROs can offer valuable insights into non-observable constructs like health literacy, self-efficacy and overall wellbeing, contributing to the comprehensive assessment of diagnosis, treatment and research end-points. Participatory community approaches, such as Community-Based Participatory, emphasise the engagement and involvement of relevant stakeholders in designing interventions tailored to their needs. Key stakeholders, including healthcare professionals, researchers, clinical trial investigators, public health officials, and community health workers, TB survivors and people with TB, can play a vital role in promoting patient-centred care and engaging directly with the TB-affected community. An increased and cross-collaborative effort for the inclusion of PROs in TB research can entail their potential role in developing effective treatment regimens and promoting adherence, while maximising community engagement and improving outcomes for those affected by TB.

Betulinic Acid for Glioblastoma Treatment: Reality, Challenges and Perspectives.

Betulinic acid is a naturally occurring compound that can be obtained through methanolic or ethanolic extraction from plant sources, as well as through chemical synthesis or microbial biotransformation. Betulinic acid has been investigated for its potential therapeutic properties, and exhibits anti-inflammatory, antiviral, antimalarial, and antioxidant activities. Notably, its ability to cross the blood-brain barrier addresses a significant challenge in treating neurological pathologies. This review aims to compile information about the impact of betulinic acid as an antitumor agent, particularly in the context of glioblastoma. Importantly, betulinic acid demonstrates selective antitumor activity against glioblastoma cells by inhibiting proliferation and inducing apoptosis, consistent with observations in other cancer types. Compelling evidence published highlights the acid's therapeutic action in suppressing the Akt/NFκB-p65 signaling cascade and enhancing the cytotoxic effects of the chemotherapeutic agent temozolomide. Interesting findings with betulinic acid also suggest a focus on researching the reduction of glioblastoma's invasiveness and aggressiveness profile. This involves modulation of extracellular matrix components, remodeling of the cytoskeleton, and secretion of proteolytic proteins. Drawing from a comprehensive review, we conclude that betulinic acid formulations as nanoparticles and/or ionic liquids are promising drug delivery approaches with the potential for translation into clinical applications for the treatment and management of glioblastoma.

Effects of cold stress on physiologic metabolism in the initial phase and performance of broiler rearing.

This study aimed to investigate the effects of 8 h of cold stress (18 °C) every day in broiler chicks during the first 7 days of rearing on crop filling analysis, yolk sac consumption, digestive and immune organs weights, and physiological metabolism at seven days and performance between 1 and 35 days. Cobb500 male broiler chickens (n = 274) were randomly assigned to two treatments. The treatments consisted of varying environmental temperatures during the first week post-housing. Chicks were reared at a thermoneutral temperature (32 °C) or under cold stress (18 °C) for 8 h/day during the first week, and both groups were subsequently reared at a thermoneutral temperature for 8-35 days. The thermoneutral group reached 90% full crop after 48 h of housing (P < 0.05), while the cold-stressed group had more empty crops at 2 h and 48 h after housing (P < 0.05). The chick cloacal temperature was not affected by the treatments (P > 0.05). Additionally, the treatment did not affect serum amylase and corticosterone levels, feed intake, body weight gain, or feed conversion ratio (P > 0.05, while the cold-stressed group had elevated heterophil/lymphocyte count at day 7 (P < 0.05). The thermoneutral group showed higher viability (%) at 7 and 35 days and a higher production factor at 35 days (P < 0.05). Broiler chickens under cyclic cold stress experienced decreased yolk sac absorption during the first week and increased feed intake and feed conversion ratio after 35 days of rearing. Viability was also lower in the cold-stressed group. An appropriate strategy to minimize these adverse effects is to rear the chicks in a thermoneutral environment during the first week.

The role of IL10 and IL17 gene polymorphisms in treatment response in children and adolescents with severe asthma.

OBJECTIVE: To determine whether polymorphisms of the IL10 and IL17 genes are associated with severe asthma control and bronchodilator reversibility in children and adolescents with severe asthma. METHODS: This was a cross-sectional study, nested within a prospective cohort study of patients with severe asthma. Two outcomes were evaluated: asthma control and bronchodilator reversibility. We extracted DNA from peripheral blood and genotyped three single nucleotide polymorphisms: rs3819024 and rs2275913 in the IL17A gene; and rs3024498 in the IL10 gene. For the association analyses, we performed logistic regression in three genetic models (allelic, additive, and dominant). RESULTS: The rs3024498 C allele in the IL10 gene was associated with failure to achieve asthma control despite regular treatment (p = 0.02). However, the G allele of the IL17A rs3819024 polymorphism was associated with failure to respond to stimulation with a b2 agonist. The rs2275913 polymorphism of the IL17A gene showed no relationship with asthma control or bronchodilator reversibility. CONCLUSIONS: In pediatric patients with severe asthma, the IL10 polymorphism appears to be associated with failure to achieve clinical control, whereas the IL17A polymorphism appears to be associated with a worse bronchodilator response. Knowledge of the involvement of these polymorphisms opens future directions for pharmacogenetic studies and for the implementation of individualized therapeutic management of severe asthma in pediatric patients.

Dissatisfaction with body image and weight gain in middle-aged women: A cross sectional study.

OBJECTIVES: To investigate the relationship between weight gain and body image perception in in middle-aged women. METHODS: Cross-sectional study with 453 women. Body image was assessed using the Stunkard scale, in which women were classified as: satisfied or dissatisfied (general, thinness or obesity). The identification of possible factors associated with body image dissatisfaction was performed using binary logistic regression analysis. RESULTS: The mean age was 55.7 (±9.6) years; 80.8% were classified as dissatisfied with body image. As for body composition, women satisfied with their body image had lower values of body fat and higher values of lean mass. In the logistic regression, for general dissatisfaction and obesity, the associated variables were BMI, education and physical activity. As for "dissatisfaction with thinness", only BMI was associated. CONCLUSION: Thus, the prevalence of body image dissatisfaction is high in women and part of associated factors are linked to lifestyle behaviors.

Fluorescent composite beads: An advanced tool for environmental monitoring and harmful pollutants removal from water.

The quality and safety of water sources have been significantly impacted by various pollutants, including trace elements. To address this concern, this study utilized composite beads made of alginate and carbon quantum dots (CDs) for detecting and removing As(III) and Se(IV) ions in tap water. Fluorescent CDs were hydrothermally synthesized and incorporated into an alginate-Ca2+ matrix through a straightforward procedure. Characterization analyses revealed distinct properties of the composite beads, containing varying amounts of CDs, compared to the pristine beads. Optimal adsorption parameters (30 mg of adsorbent, 10 mg/L of initial pollutant concentration, 35 °C, and 180 min of contact time) for the beads containing 30 w/w-% of CDs (Alg@CDs30) were determined through a fractional factorial design. These composite beads exhibited the highest adsorption capacity for both metals, achieving a removal rate of 94.5% for As(III) and 98.0% for Se(IV) in tap water. Kinetic and isothermal analyses indicated that the adsorption of both metals on Alg@CDs30 involves a combination of chemisorption and diffusion processes. Recycling experiments demonstrated that the composite beads could be reused up to 20 times without a noticeable loss of adsorption efficiency. Regarding the sensing property, our experiments revealed a significant reduction in the fluorescence emission intensity of Alg@CDs30 upon interaction with As(III) and Se(IV), confirming its ability to detect both ions in tap water, with limits of detection (LOD) of 2.6 ± 0.5 µg/L for As(III) and 1.1 ± 0.2 µg/L for Se(IV). The alginate-Ca2+ matrix s contributed to the stability of the CDs' fluorescence. These results confirm the potential of Alg@CDs beads as effective tools for the simultaneous monitoring and removal of hazardous metal ions from real water samples.

Building bridges: multidisciplinary teams in tuberculosis prevention and care.

People with or affected by tuberculosis (TB) experience complex social and cultural constraints that may affect treatment outcomes by impeding access to proper care or by hindering treatment adherence. Low levels of health literacy which leads to inadequate disease information; stigma, discrimination and other forms of prejudice that may result in marginalisation and ostracisation; and socioeconomic vulnerabilities that hamper one's capacity to access essential goods or increase the risk of exposure to the disease are some of the barriers highlighted. These complex hurdles are also disproportionately felt by people with or affected by TB due to gender-related inequalities that need to be properly addressed. Additionally, TB prevention and care should encompass interventions aimed at improving and promoting mental health, given that mental unhealth may further thwart treatment adherence and success. A multifaceted and multidisciplinary approach to TB is required to answer these complex barriers.

Compartmentalized Regulation of Pulmonary and Systemic Inflammation in Critical COVID-19 Patients.

Critical COVID-19 has been associated with altered patterns of cytokines. Distinct inflammatory processes in systemic and pulmonary sites have been reported, but studies comparing these two sites are still scarce. We aimed to evaluate the profile of pulmonary and systemic cytokines and chemokines in critically ill COVID-19 patients. Levels of cytokines and chemokines were measured in plasma samples and minibronchoalveolar lavage of critical COVID-19 patients within 48 h and 5-8 days after intubation. Distinct inflammatory processes were observed in the lungs and blood, which were regulated separately. Survivor patients showed higher lung cytokine levels including IFN-γ, IL-2, IL-4, G-CSF, and CCL4, while nonsurvivors displayed higher levels in the blood, which included IL-6, CXCL8, CXCL10, CCL2, and CCL4. Furthermore, our findings indicate that high TNF and CXCL8 levels in the mini-BAL were associated with better lung oxygen exchange capacity, whereas high levels of IFN-γ in plasma were associated with worse lung function, as measured using the PaO2/FiO2 ratio. These results suggest that a robust and localized inflammatory response in the lungs is protective and associated with survival, whereas a systemic inflammatory response is detrimental and associated with mortality in critical COVID-19.

Thirteen years of experience with eslicarbazepine acetate in the United Kingdom and Republic of Ireland: A safety perspective.

OBJECTIVE: Eslicarbazepine acetate (ESL) is a once-daily oral antiseizure medication. Its safety and tolerability from clinical trials have been mostly confirmed by real-world data. The main purpose of this report is to provide an overview of the safety profile of ESL in the United Kingdom (UK) and Republic of Ireland (ROI). METHODS: Safety data were obtained from the UK and ROI post-marketing sources (October 2009-April 2022) by the marketing authorization holder. All individual reports were included in the Argus Safety™ database. All adverse events (AEs) were coded using MedDRA® version 24.1. Only valid cases (meeting the minimum pharmacovigilance reporting requirements) were included. RESULTS: During 13 years of ESL marketing, with cumulative estimated exposure of 2 210 395 patients-years, 183 reports were received. A total of 402 AEs were reported for the 155 valid reports. The most common reported AEs (≥6% of total reported), per system organ class (SOC), were: nervous system disorders (23.4%), injury, poisoning, and procedural complications (18.9%), general disorders and administration site conditions (12.9%), psychiatric disorders (12.7%) and gastrointestinal disorders (6.7%). The most frequently reported (≥2% of total reported) AEs were: seizure (4.5%), hyponatremia (4.2%), dizziness (2.7%), rash, fatigue (2.5% each), and somnolence (2.0%). Twenty-six percent of events were classified as serious (including six fatal cases). SIGNIFICANCE: The current analysis supports the known safety profile of ESL, as generally well-tolerated with most AEs being non-serious. The most common AEs were considered either expected according to the disease itself or to the reference safety information. ESL continues to be a relevant medication in the treatment of partial (focal-onset) epilepsy, as also confirmed by the 2022 NICE guidelines.

Composite hydrogel based on alginate-g-poly(acrylamide)/carbon nanotubes for solid phase extraction of metals from corn cereal samples.

Composite hydrogels containing nanofillers are extensively applied in the sorption of different compounds from aqueous solutions; however, this ability is poorly exploited in the extraction and pre-concentration of analytes from complex matrices. As a contribution to this field, this study reports the synthesis of a composite hydrogel of alginate-g-poly(acrylamide) matrix filled with functionalized multi-walled carbon nanotubes (ALG-g-PAAM/MWCNT-f). This composite served as a solid-phase extractor (SPE) for the separation of Pb2+ and Cd2+ ions from a digested corn cereal sample before their analytical determination. After composite characterization, a series of experiments using low dosages of ALG-g-PAAM/MWCNT-f demonstrated that the composite has a higher sorption capacity for Pb2+ (5.1 mg/g) and Cd2+ (3.9 mg/g) under favorable experimental conditions. As demonstrated, the presence of the MWCNT-f benefited the SPE performance of the composite. The sorption of both cations followed the pseudo-first order kinetics, while the experimental data were well-fitted by the Freundlich isotherm. Also, ALG-g-PAAM/MWCNT-f showed selectivity for Pb2+, and it is reusable up to 10 times without losing sorption performance. After sorption and extraction, both metals were completely recovered, facilitating their quantification by the MIP OES technique. In short, ALG-g-PAAM/MWCNT-f was an effective SPE for the separation and extraction of Pb2+ and Cd2+, which can be beneficial for food control and safety.

Combined computational and experimental study about the incorporation of phosphorus into the structure of graphene oxide.

Phosphorus-containing graphene-based hybrids are materials with outstanding properties for diverse applications. In this work, an easy route to produce phosphorus-graphene oxide hybrid materials is described, involving the use of variable amounts of H3PO4 and H2SO4 during the reaction of oxidation of a graphitic precursor. The physical and chemical features of the hybrids change significantly with the variation in the acid amounts used in the syntheses. XPS and solid-state 13C and 31P NMR results show that the hybrids contain large amounts of oxygen functional groups, with the phosphorus incorporation proceeding mostly through the formation of phosphate-like linkages and other functions with C-O-P bonds. The experimental findings are supported by DFT calculations, which allow the assessment of the energetics and the geometry of the interaction between phosphate groups and graphene-based models; these calculations are also used to predict the chemical shifts in the 31P and 13C NMR spectra of the models, which show good agreement with the experimentally observed solid-state NMR spectra.

Diagnostic Accuracy of the Short Physical Performance Battery in Detecting Frailty and Prefrailty in Community-Dwelling Older Adults: Results From the PRO-EVA Study.

BACKGROUND AND PURPOSE: The Short Physical Performance Battery (SPPB) is widely used for older adults since it has a high level of validity, reliability, and responsiveness in measuring function in this population. However, only a few studies of diagnostic accuracy have assessed SPPB capacity in detecting frailty and prefrailty by estimating more detailed measurement properties. Thus, the present study aimed to evaluate the SPPB's diagnostic accuracy in detecting frailty and prefrailty, in addition to identifying cut-off points for walking time and chair stand time. METHODS: This is a cross-sectional study composed of 786 community-dwelling older adults 60 years or older, in which sociodemographic and anthropometric data, frailty phenotype, and total SPPB score, as well as walking time and chair stand time, were assessed. Analysis of a receiver operating characteristic curve was performed to identify the cut-off point, sensitivity, and specificity in the total SPPB score, as well as the walking time and chair stand time for frailty and prefrailty screening. Accuracy and positive and negative predictive values were subsequently calculated. RESULTS AND DISCUSSION: The cut-off points identified for the total SPPB score, walking time, and chair stand time were 9 points or less (accuracy of 72.6%), 5 seconds or less, and 13 seconds or less, respectively, for frailty screening and 11 points or less (accuracy of 58.7%), 4 seconds or less, and 10 seconds or less, respectively, for prefrailty screening. The walking time showed greater frailty discriminatory capacity compared with the chair stand time (effect size = 1.24 vs 0.64; sensitivity = 69% vs 59%; and specificity = 84% vs 75%). CONCLUSIONS: The total SPPB score has good diagnostic accuracy to discriminate between nonfrail and frail older adults using a cut-off point of 9 or less, being better to identify the true negatives (older adults who are not frail). Although the SPPB's diagnostic accuracy measures for detecting prefrailty were low to moderate, this instrument can help in screening prefrail older adults from the cutoff point of 11 or less in the total SPPB score. Identification of prefrail older adults enables implementing early treatment in this target audience and can prevent their advance to frailty.

Biomarkers in Hypertension and Hypertension-related Disorders.

Systemic arterial hypertension (SAH) is a major risk factor for several secondary diseases, especially cardiovascular and renal conditions. SAH has a high prevalence worldwide, and its precise and early recognition is important to prevent the development of secondary outcomes. In this field, the study of biomarkers represents an important approach to diagnosing and predicting the disease and its associated conditions. The use of biomarkers in hypertension and hypertension-related disorders, such as ischemic stroke, intracerebral hemorrhage, transient ischemic attack, acute myocardial infarction, angina pectoris and chronic kidney disease, are discussed in this review. Establishing a potential pool of biomarkers may contribute to a non-invasive and improved approach for their diagnosis, prognosis, risk assessment, therapy management and pharmacological responses to a therapeutic intervention to improve patients' quality of life and prevent unfavorable outcomes.

Dysfunctional phenotype of systemic and pulmonary regulatory T cells associate with lethal COVID-19 cases.

Severe cases of COVID-19 present hyperinflammatory condition that can be fatal. Little is known about the role of regulatory responses in SARS-CoV-2 infection. In this study, we evaluated the phenotype of regulatory T cells in the blood (peripheral blood mononuclear cell) and the lungs (broncho-alveolar) of adult patients with severe COVID-19 under invasive mechanical ventilation. Our results show important dynamic variation on Treg cells phenotype during COVID-19 with changes in number and functional parameters from the day of intubation (Day 1 of intensive care unit admission) to Day 7. We observed that compared with surviving patients, non-survivors presented lower numbers of Treg cells in the blood. In addition, lung Tregs of non-survivors also displayed higher PD1 and lower FOXP3 expressions suggesting dysfunctional phenotype. Further signs of Treg dysregulation were observed in non-survivors such as limited production of IL-10 in the lungs and higher production of IL-17A in the blood and in the lungs, which were associated with increased PD1 expression. These findings were also associated with lower pulmonary levels of Treg-stimulating factors like TNF and IL-2. Tregs in the blood and lungs are profoundly dysfunctional in non-surviving COVID-19 patients.

Unveiling the power of neutral and inclusive language in tuberculosis prevention and care.

Language plays a crucial role in shaping discourses and responses related to disease, particularly tuberculosis (TB). Stigmatising language and attitudes surrounding TB can lead to discrimination and marginalisation of affected individuals, creating barriers to seeking proper diagnosis and treatment. The terminology used to describe TB-affected individuals can be disempowering and criminalising, reinforcing an "othering" of those affected. To combat this, engaging with TB-affected communities is essential to co-construct a neutral and inclusive vocabulary that respects the dignity of individuals and fosters empathy and support. Thus, an inclusive language approach empowers affected individuals as active participants in their health management, encouraging open communication and the development of support networks. By adopting a neutral and inclusive language system, healthcare providers and communities can work together to remove unnoticed hurdles and align with the World Health Organization's TB care and prevention goals.

The role of IL10 and IL17 gene polymorphisms in treatment response in children and adolescents with severe asthma / O papel de polimorfismos dos genes IL10 e IL17 na resposta ao tratamento em crianças e adolescentes com asma grave

ABSTRACT Objective: To determine whether polymorphisms of the IL10 and IL17 genes are associated with severe asthma control and bronchodilator reversibility in children and adolescents with severe asthma. Methods: This was a cross-sectional study, nested within a prospective cohort study of patients with severe asthma. Two outcomes were evaluated: asthma control and bronchodilator reversibility. We extracted DNA from peripheral blood and genotyped three single nucleotide polymorphisms: rs3819024 and rs2275913 in the IL17A gene; and rs3024498 in the IL10 gene. For the association analyses, we performed logistic regression in three genetic models (allelic, additive, and dominant). Results: The rs3024498 C allele in the IL10 gene was associated with failure to achieve asthma control despite regular treatment (p = 0.02). However, the G allele of the IL17A rs3819024 polymorphism was associated with failure to respond to stimulation with a b2 agonist. The rs2275913 polymorphism of the IL17A gene showed no relationship with asthma control or bronchodilator reversibility. Conclusions: In pediatric patients with severe asthma, the IL10 polymorphism appears to be associated with failure to achieve clinical control, whereas the IL17A polymorphism appears to be associated with a worse bronchodilator response. Knowledge of the involvement of these polymorphisms opens future directions for pharmacogenetic studies and for the implementation of individualized therapeutic management of severe asthma in pediatric patients.

RESUMO Objetivo: Determinar se existe relação entre polimorfismos dos genes IL10 e IL17 e controle da asma grave e reversibilidade com broncodilatador em crianças e adolescentes com asma grave. Métodos: Estudo transversal, aninhado em um estudo prospectivo de coorte com pacientes com asma grave. Foram avaliados dois desfechos: controle da asma e reversibilidade com broncodilatador. Extraímos DNA do sangue periférico e genotipamos três polimorfismos de nucleotídeo único: rs3819024 e rs2275913 no gene IL17A e rs3024498 no gene IL10. Para as análises de associação, realizamos regressão logística em três modelos genéticos (alélico, aditivo e dominante). Resultados: O alelo C do polimorfismo rs3024498 do gene IL10 apresentou relação com asma que permaneceu descontrolada mesmo com tratamento regular (p = 0,02). No entanto, o alelo G do polimorfismo rs3819024 do gene IL17A apresentou relação com ausência de resposta ao estímulo com b2-agonista. O polimorfismo rs2275913 do gene IL17A não apresentou relação com controle da asma ou reversibilidade com broncodilatador. Conclusões: Em pacientes pediátricos com asma grave, o polimorfismo do gene IL10 parece estar relacionado com ausência de controle clínico, ao passo que o polimorfismo do gene IL17A parece estar relacionado com pior resposta ao broncodilatador. O conhecimento a respeito do envolvimento desses polimorfismos abre perspectivas futuras para estudos farmacogenéticos e para a implantação de manejo terapêutico individualizado da asma grave em pacientes pediátricos.

Muscle strength is associated with fracture risk obtained by fracture risk assessment tool (FRAX) in women with breast cancer.

BACKGROUND: Women with breast cancer are at risk for the development of sarcopenia and occurrence of fractures. The initial and periodic screening of these conditions can prevent the risks of disability, poor quality of life, and death. The present study investigated the association between sarcopenia phenotypes and fracture risk, assessed by the Fracture Risk Assessment Tool (FRAX) in women with breast cancer. METHODS: Cross-sectional study. It included women aged between 40 and 80 years, diagnosed with Luminal subtype breast cancer, with time of diagnosis ≤ 12 months, who had not started endocrine therapy, did not have metastasis, had not been treated for another malignancy, and had no recurrences. Sociodemographic, habits and lifestyle, clinical, anthropometric, and body composition variables were considered. Muscle strength, skeletal muscle mass, and physical performance were investigated using handgrip strength (HGS), appendicular skeletal muscle mass index (ASMI), and Timed Up and Go test (TUGT), respectively. Fracture risk was assessed using FRAX. Multiple linear regression models were conducted to verify the association between exposure variables and sarcopenia phenotypes. A significance level of p < 0.05 was adopted for all tests using the SPPS 25.0 program. RESULTS: Sixty-two women with a mean age of 58.1 ± 10.4 years were evaluated. Of these, 66.1% self-declared to be non-white, 41.9% and 71.0% did not consume alcohol or smoke, respectively, and 61.3% were insufficiently active. A total of 45.2% had clinical stage II carcinoma and 65.5% had the invasive breast carcinoma histological subtype. There was a predominance of adequacy of HGS (88.7%), ASMI (94.5%), and TUGT (96.8%), as well as low risk of hip fractures (85.5%) and major fractures (82.3%). HGS remained associated with FRAX hip fractures (p = 0.007) and FRAX major fractures (p = 0.007) in the adjusted models, while ASMI was associated with body mass (p < 0.001). CONCLUSIONS: Low muscle strength was the sarcopenia phenotype that remained associated with fracture risk in women with breast cancer, independently of sociodemographic factors, level of physical activity, and clinical factors. In addition to the assessment of probable sarcopenia, this measurement may point out the risk of fractures.