INTRODUCTION Mepolizumab was the first licensed anti-IL5 mAb for severe eosinophilic asthma (SEA). To date there is little data to confirm its efficacy in the real-world setting or assessment of baseline characteristics associated with response. METHODS We conducted a retrospective review of all patients who received at least 16 weeks of treatment with mepolizumab (100mg sc) for SEA at our regional asthma centre in the UK. Clinical data was collected at each 4-weekly visit. At 16, 24 and 52 weeks, patients were classified as ‘responders’ or ‘non-responders’. A response was defined as ≥50% reduction in exacerbations, or for patients requiring maintenance oral corticosteroids (mOCS), ≥50% reduction in prednisolone dose. Super-responders were defined as exacerbation-free and off mOCS at one year. RESULTS 99 patients were included in the analysis. Asthma exacerbations decreased from a baseline of 4.04(2.57) to 1.86(2.17) at 1 year (54% reduction, p less then 0.001). 68 subjects were on mOCS at the time of commencing mepolizumab. By one year the daily median dose fell from 10mg (IQR 10-15) to 0mg (IQR 0-10, p less then 0.001). 57% were able to discontinue mOCS. 72.7% (95%CI 63.0-80.7) patients were classified as responders and 28.3% (95%CI 20.2-38.0) as super-responders. Baseline characteristics associated with responder and super-responder status included the presence of nasal polyposis (p=0.012), lower baseline ACQ6 (p=0.006), a lower BMI (p=0.014), and in those on mOCS a significantly lower prednisolone dose at baseline (p=0.005). At 16 weeks, the 1-year responder status was correctly identified in 80.8% patients and by 24 weeks this rose to 92.9%. CONCLUSION In a real-world SEA cohort, treatment with mepolizumab reduced exacerbation frequency and mOCS requirements. Nasal polyposis, a lower BMI and a lower maintenance prednisolone requirement at baseline were associated with better outcomes. Twelve-month response was identifiable in over 90% of patients by week 24. BACKGROUND Elevated surfactant protein D (SP-D) is a relatively specific indicator of lung injury and is associated with both acute and chronic lung disease in adults and respiratory distress syndrome in premature infants. The relationship between plasma SP-D and lung injury in children with acute respiratory failure is unclear. RESEARCH QUESTION Is plasma SP-D associated with lung injury or outcome in children with acute respiratory failure? STUDY DESIGN AND METHODS This was a prospective cohort study in children 2 weeks to 17 years of age with acute respiratory failure who participated in the BALI multi-center study. Analyses were done using SP-D levels in plasma from the first sample taken on either the day of intubation or one of the following 2 days. SP-D level was measured by ELISA. RESULTS Plasma samples from 350 patients were used in the analysis, 233 had pediatric acute respiratory distress syndrome (PARDS). SP-D levels varied across primary diagnoses (p less then 0.001). Elevated SP-D levels were associated with severe PARDS after adjusting for age, PRISM-III and primary diagnosis (OR=1.02, CI=1.01-1.04, p=0.011). Multivariable analyses also indicated that elevated SP-D levels were associated with death (OR=1.02, CI=1.01-1.04, p=0.004), duration of mechanical ventilation (p=0.012), PICU length of stay (p=0.019), and highest oxygenation index (p=0.040). SP-D levels also correlated with age (rs=0.16, p=0.002). INTERPRETATION Elevated plasma SP-D levels are associated with severe PARDS and poor outcomes in children with acute respiratory failure. Future studies will determine whether SP-D can be used to predict the degree of lung injury and/or response to treatment and whether SP-D is useful in identifying PARDS endotypes. With more than 900,000 confirmed cases worldwide and nearly 50,000 deaths during the first three months of 2020, the COVID-19 pandemic has emerged as an unprecedented healthcare crisis. The spread of COVID-19 has been heterogeneous, resulting in some regions having sporadic transmission and relatively few hospitalized patients with COVID-19 and others having community transmission that has led to overwhelming numbers of severe cases. For these regions, healthcare delivery has been disrupted and compromised by critical resource constraints in diagnostic testing, hospital beds, ventilators, and healthcare workers who have fallen ill to the virus exacerbated by shortages of personal protective equipment. While mild cases mimic common upper respiratory viral infections, respiratory dysfunction becomes the principal source of morbidity and mortality as the disease advances. Thoracic imaging with chest radiography (CXR) and computed tomography (CT) are key tools for pulmonary disease diagnosis and management, but t9. Cancer-associated fibroblasts (CAFs) are an important component of the tumor microenvironment and mediate tumor progression in various cancers. A previous study demonstrated that TRAF6 promotes melanoma cells’ malignant phenotype. LY-188011 However, the role of TRAF6 in melanoma CAFs remains unclear. In this study, we found that TRAF6 is significantly upregulated in CAFs adjacent to melanoma cells. Functional assays demonstrated that TRAF6 promotes fibroblast proliferation and migration as well as MMP and α-SMA expression. Moreover, the expression of TRAF6 in fibroblasts promoted the malignant phenotype of melanoma cells in vitro and in vivo. Meanwhile, the intervention of TRAF6 expression in melanoma cells affected the activation of CAFs. We found that FGF19 is a key cytokine regulated by TRAF6 through NF-κB1 using luciferase assay and chromatin immunoprecipitation in melanoma cells. Since plasma FGF19 levels are elevated in melanoma patients, it may significantly induce fibroblast activation in vitro and in vivo. Taken together, our results support that TRAF6 is a key molecule that mediates the interaction between melanoma cells and stromal fibroblasts, suggesting that TRAF6 is a potentially promising target in melanoma therapy. Breslow thickness (BT) is the most important histopathologic factor for primary melanoma staging. Breslow thickness determines the margins for wide local excision, whether sentinel lymph node biopsy should be performed and subsequent melanoma staging and patient management. The correct determination of a 0.8 mm cut-off in melanoma is important for pathologists since discrepancies leading to a change in stage can have significant clinical implications, including incorrect/inappropriate prognostic information, investigation, management and follow-up. Difficulties in Breslow thickness determination are mostly represented by the presence of regression, or melanoma associated with a pre-existing nevus.