Expression of HIF-1α in pediatric asthmatic patients.

Background: Several studies have suggested that HIF-1α regulates eosinophil activity and induces epithelial inflammation via NF-κB activation in the pathophysiology of asthma. The purpose of this study was to examine the expression of the transcription factors HIF-1α and nuclear HIF in mononuclear cells obtained from peripheral blood samples of healthy pediatric patients, asthmatic patients, and asthmatic exacerbations, regardless of disease severity. Methods: HIF-1 levels were measured using immunocytochemistry in 133 patients aged 6 to 17 years in this crosssectional and comparative study. A microscope was used to examine glass slides, and positive cells were counted in four fields per slide using an image analyzer. Results: HIF-1α and nuclear HIF levels were significantly higher in asthma patients and even higher in patients experiencing asthma attacks (p<0.0001, 95% CI). There was no significant difference in the percentage of HIF-1α expression between groups with intermittent asthma and those with mild persistent asthma, nor between patients with asthma and those experiencing asthma exacerbations. Conclusions: When compared to healthy individuals, the expression of nuclear HIF and HIF-1α is increased in peripheral mononuclear cells in asthma patients and even more so in asthma exacerbations. This suggests that HIF-1α is important in the pathogenesis of this disease.

Asthma exacerbations in the pediatric emergency area: Evaluation and prospects for improvement of pre-hospital care.

INTRODUCTION: The frequency of visits to emergency department for asthma is a significant public health problem in pediatrics. This study aimed to identify the characteristics of children who visited the pediatric emergency department for asthma exacerbation and evaluated their therapeutic management prior to admission. METHODS: A prospective study was conducted over a 6-month period in the pediatric emergency departments of five hospitals involving children aged 1-16 years admitted to the department with a clinical diagnosis of asthma exacerbation. RESULTS: In all, 143 patients were enrolled in the study. Asthma episodes were moderate to severe in 69.2% of cases (n = 99). Initial treatment prior to admission to the emergency department was adequate in only 17.5% of cases (n = 25). Hospitalization for more than 24 h occurred in 18.2% (n = 26) patients. In children aged <3 years, viral infection was present in 91.4% cases (n = 64) and exacerbations were more severe in younger patients (P = 0.002) and children belonging to low-income stratum (P = 0.025). Only 17.4% (n = 25) were positive for SARS-CoV-2 (antigen test or polymerase chain reaction test), suggesting that the involvement of traditional respiratory viruses in asthma exacerbation continued even during pandemic. Regarding the pre-hospital care, 70.6% (n = 101) had received prior treatment, but this treatment was inadequate in 53.1% cases (n = 76). CONCLUSION: This study showed that asthmatic children and their families had little knowledge about the disease and that physicians must be sufficiently aware of current recommendations for managing asthmatic children. Admission to the emergency department for asthma could be avoided partially by better diagnosis and therapeutic education.

Articular involvement in Henoch-Schönlein Purpura: A review of literature.

BACKGROUND: Henoch-Schönlein purpura (HSP), the most typical kind of pediatric vasculitis, can also affect adults. Over the last 10 years, research has been increasing on improvements in HSP diagnosis, physiopathology, symptoms, and therapy. Joint involvement is highly frequent in this condition; however, it typically undergoes spontaneous resolution and does not lead to long-term complications. OBJECTIVE: To provide a deeper understanding of the constituting pathogenic mechanisms and clinical presentation of articular involvement, focusing on the effect of neutrophil activation on systemic small vessels. METHODS: This literature review utilized a systematic search of academic databases, employing specific keywords to select recent peer-reviewed articles and scholarly sources on the topic. RESULTS: The manifestations of joint involvement in HSP can vary in severity and frequency. Non-steroidal anti-inflammatory medications or acetaminophen are considered the first-line treatment for joint pain; however, corticosteroids may help achieve quick remission. In cases where standard treatment fails or manifestations persist, immunosuppressive drugs like rituximab, methotrexate, cyclophosphamide, or azathioprine have been used. CONCLUSIONS: While it tends to resolve without lasting joint damage, accurate diagnosis and appropriate management are crucial to ensure optimal patient outcomes.

Comorbidities & burden of disease in atopic dermatitis.

BACKGROUND: Atopic dermatitis is associated with an increased frequency of other atopic & allergic manifestations, including asthma in 10% to 30% of cases depending on age, allergic rhinitis, food allergies, eosinophilic diseases, and allergic conjunctivitis. The comorbidities outside the atopic march are overall less frequent than in psoriasis. OBJECTIVE: This review aims to demonstrate the intense, broad burden of this disease, comorbidities and its multidimensional involvement as a complex, heterogeneous disease. METHODS: Methods: The present narrative review summarizes the findings from the world's largest epidemiological studies and smaller, AD-specific studies on the comorbidities and burdens of this disease. RESULTS: Results: The risk of asthma, specifically, and other atopic manifestations and skin infections, generally, is clearly increased among patients with AD. Of the other skin diseases, there is an undeniable risk of alopecia areata, vitiligo, and contact eczema and a lower risk of developing other autoimmune diseases. While comorbidities exist, their frequency seems to be modified by lifestyle, particularly by smoking. There is a link with overweight, obesity, and metabolic syndrome, especially in severe AD. This is also the case for cardiovascular diseases; however, with OR/HRs below 1.5. There is no link to type II diabetes but, rather, to type I in children. In all other areas, the data are often inconsistent, and any increase in risk is low. Eye diseases seem to be the only exception. AD also has psychiatric consequences, including attention-hyperactivity disorder, anxiety, depression, and sometimes suicidality, especially when severe. CONCLUSIONS: Conclusions: The recently published work largely confirms our existing understanding of AD.

The Pan-TRK Antibody is a Sensitive and Specific Tool for the Detection of NTRK Fusion Genes.

Pan-TRK antibodies have been used to detect gene fusions in diverse types of tumors. Several tyrosine receptor kinases (TRK) inhibitors have recently been developed and have shown good response rates in neoplasms with NTRK; therefore, identifying these fusions is an essential tool in assessing treatment options for certain oncological diseases. Various algorithms have been designed to diagnose and detect NTRK fusions to optimize time and resources. This study explores the use of immunohistochemistry (IHC) as a screening method for NTRK fusions by comparing next-generation sequencing (NGS) and IHC to evaluate the pan-TRK antibody's performance as a marker for NTRK rearrangements. The present work studied 164 formalin-fixed paraffin-embedded blocks of different solid tumors. Two pathologists confirmed the diagnosis and selected the correct area to assess with IHC and NGS. Specific cDNAs were generated for the genes involved. NTRK fusions were identified in 4 patients positive for the pan-TRK antibody through NGS. The identified fusions were NTRK1-TMP3, NTRK3-EML4, and NTRK3-ETV6. That shows sensitivity and specificity of 100% and 98%, respectively. NTRK fusions were identified in 4 patients positive for the pan-TRK antibody through NGS. IHC tests (with the pan-TRK antibody) are a sensitive and specific method for identifying the presence of NTRK1-3 fusions.

Asthma exacerbations in the pediatric emergency area: Evaluation and prospects for improvement of pre-hospital care

Introduction: The frequency of visits to emergency department for asthma is a significant public health problem in pediatrics. This study aimed to identify the characteristics of children who visited the pediatric emergency department for asthma exacerbation and evaluated their therapeutic management prior to admission. Methods: A prospective study was conducted over a 6-month period in the pediatric emergency departments of five hospitals involving children aged 1–16 years admitted to the department with a clinical diagnosis of asthma exacerbation. Results: In all, 143 patients were enrolled in the study. Asthma episodes were moderate to severe in 69.2% of cases (n = 99). Initial treatment prior to admission to the emergency department was adequate in only 17.5% of cases (n = 25). Hospitalization for more than 24 h occurred in 18.2% (n = 26) patients. In children aged <3 years, viral infection was present in 91.4% cases (n = 64) and exacerbations were more severe in younger patients (P = 0.002) and children belonging to low-income stratum (P = 0.025). Only 17.4% (n = 25) were positive for SARS–CoV-2 (antigen test or polymerase chain reaction test), suggesting that the involvement of traditional respiratory viruses in asthma exacerbation continued even during pandemic. Regarding the pre-hospital care, 70.6% (n = 101) had received prior treatment, but this treatment was inadequate in 53.1% cases (n = 76). Conclusion: This study showed that asthmatic children and their families had little knowledge about the disease and that physicians must be sufficiently aware of current recommendations for managing asthmatic children. Admission to the emergency department for asthma could be avoided partially by better diagnosis and therapeutic education (AU)

IL-10 suppressor activity and ex vivo Tr1 cell function are impaired in multiple sclerosis.

T regulatory cells type 1 (Tr1 cells) are excellent candidates for cell therapy in multiple sclerosis (MS). The aim of our study was to assess the functional state of Tr1 cells and IL-10R signaling in patients with MS. Tr1 cells were induced in vitro by activation with anti-CD46 antibodies in controls and patients with MS. Cells were phenotyped by cytometry and suppression assays, and the expression of cytokines and transcription factors was evaluated by real-time PCR, ELISA, cytometry and Western blotting. We found that the activity of Tr1 cells and IL-10R signaling is impaired in MS patients since Tr1 cells isolated from MS patients produced less IL-10 than those obtained from controls. Indeed, the supernatants from Tr1 cells from controls did not suppress the proliferation of stimulated CD4(+) cells from patients with MS. Furthermore, the IL-10R signaling pathway was not fully active in CD4(+) cells from MS patients and these cells had higher baseline levels of SOCS3 transcripts than controls. Indeed, after in vitro IL-10 stimulation, the expression levels of the STAT1, STAT3 and IL-10RA genes were higher in MS patients than in controls. Moreover, Stat-3 phosphorylation was lower in controls than in patients after IL-10 stimulation. These results indicate that IL-10 regulatory function is impaired in patients with MS.