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Introduction Chronic hyperglycemia affects neutrophil functions, leading to reduced pathogen killing and increased morbidity. This impairment has been directly linked to increased glycemia, however, how this specifically affects neutrophils metabolism and their differentiation in the bone marrow is unclear and difficult to study.Research design and methods We used high-resolution respirometry to investigate the metabolism of resting and activated donor neutrophils, and flow cytometry to measure surface CD15 and CD11b expression. We then used HL-60 cells differentiated towards neutrophil-like cells in standard media and investigated the effect of doubling glucose concentration on differentiation metabolism. We measured the oxygen consumption rate (OCR), and the enzymatic activity of carnitine palmitoyl transferase 1 (CPT1) and citrate synthase during neutrophil-like differentiation. We compared the surface phenotype, functions, and OCR of neutrophil-like cells differentiated under both glucose concentrations.Results Donor neutrophils showed significant instability of CD11b and OCR after phorbol 12-myristate 13-acetate stimulation at 3 hours post-enrichment. During HL-60 neutrophil-like cell differentiation, there was a significant increase in surface CD15 and CD11b expression together with the loss of mitochondrial mass. Differentiated neutrophil-like cells also exhibited higher CD11b expression and were significantly more phagocytic. In higher glucose media, we measured a decrease in citrate synthase and CPT1 activities during neutrophil-like differentiation.Conclusions HL-60 neutrophil-like differentiation recapitulated known molecular and metabolic features of human neutrophil differentiation. Increased glucose concentrations correlated with features described in hyperglycemic donor neutrophils including increased CD11b and phagocytosis. We used this model to describe metabolic features of neutrophil-like cell differentiation in hyperglycemia and show for the first time the downregulation of CPT1 and citrate synthase activity, independently of mitochondrial mass.

Objectives Real-world data regarding rheumatoid arthritis (RA) and its association with interstitial lung disease (ILD) is still scarce. This study aimed to estimate the prevalence of RA and ILD in patients with RA (RAILD) in Spain, and to compare clinical characteristics of patients with RA with and without ILD using natural language processing (NLP) on electronic health records (EHR).Methods Observational case–control, retrospective and multicentre study based on the secondary use of unstructured clinical data from patients with adult RA and RAILD from nine hospitals between 2014 and 2019. NLP was used to extract unstructured clinical information from EHR and standardise it into a SNOMED-CT terminology. Prevalence of RA and RAILD were calculated, and a descriptive analysis was performed. Characteristics between patients with RAILD and RA patients without ILD (RAnonILD) were compared.Results From a source population of 3 176 165 patients and 64 241 683 EHRs, 13 958 patients with RA were identified. Of those, 5.1% patients additionally had ILD (RAILD). The overall age-adjusted prevalence of RA and RAILD were 0.53% and 0.02%, respectively. The most common ILD subtype was usual interstitial pneumonia (29.3%). When comparing RAILD versus RAnonILD patients, RAILD patients were older and had more comorbidities, notably concerning infections (33.6% vs 16.5%, p

Background The recent outbreak of COVID-19 has raised concerns in the rheumatology community about the management of immunosuppressed patients diagnosed with inflammatory rheumatic diseases. It is not clear whether the use of biological agents may suppose a risk or protection against SARS-CoV-2 infection; however, it has been suggested that severe respiratory forms of COVID-19 occur as a result of exacerbated inflammation status and cytokine production. This prompted the use of interleukin 6 (IL-6) (tocilizumab and sarilumab) and IL-1 inhibitors (anakinra) in severe COVID-19 disease and more recently JAK1/2 inhibitor (baricitinib). Therefore, patients with rheumatic diseases provide a great opportunity to learn about the use of biological agents as protective drugs against SARS-CoV-2.Objectives To estimate COVID-19 infection rate in patients treated with biological disease-modifying antirheumatic drugs (bDMARDs) for inflammatory rheumatic diseases (RMD), determine the influence of biological agents treatment as risk or protective factors and study the prognosis of patients with rheumatic diseases receiving biological agents compared to the general population in a third-level hospital setting in León, Spain.Methods We performed a retrospective observational study including patients seen at our rheumatology department who received bDMARDs for rheumatic diseases between December 1st 2019 and December 1st 2020, and analysed COVID-19 infection rate. All patients who attended our rheumatology outpatient clinic with diagnosis of inflammatory rheumatic disease receiving treatment with biological agents were included. Main variable was the hospital admission related to COVID-19. The covariates were age, sex, comorbidities, biological agent, duration of treatment, mean dose of glucocorticoids and need for intensive care unit . We performed an univariate and multivariate logistic regression models to assess risk factors of COVID-19 infection.Results There were a total of 4464 patients with COVID-19 requiring hospitalisation. 40 patients out of a total of 820 patients with rheumatic diseases (4.8%) receiving bDMARDs contracted COVID-19 and 4 required hospital care. Crude incidence rate of COVID-19 requiring hospital care among the general population was 3.6%, and it was 0.89% among the group with underlying rheumatic diseases. 90% of patients receiving bDMARDS with COVID-19 did not require hospitalisation. Out of the 4464 patients, 869 patients died, 2 of which received treatment with biological agents. Patients with rheumatic diseases who tested positive for COVID-19 were older (female: median age 60.8 IQR 46-74; male: median age 61.9 IQR 52-70.3) than those who were negative for COVID-19 (female: median age 58.3 IQR 48-69; male: median age 56.2 IQR 47-66), more likely to have hypertension (45% vs 26%, OR 2.25 (CI 1.18-4.27),p 0.02), cardiovascular disease (23 % vs 9.6%, OR 2.73 (1.25-5.95), p 0.02), be smokers (13% vs 4.6%, OR 2.95 (CI 1.09-7.98), p 0.04), receiving treatment with rituximab (20% vs 8%, 2.28 (CI 1.24-6.32), p 0.02) and a higher dose of glucocorticoids (OR 2.5 (1.3-10.33, p 0.02) and were less likely to be receiving treatment with IL-6 inhibitors (2.5% vs 14%, OR 0.16, (CI 0.10-0.97, p 0.03). When exploring the effect of the rest of the therapies between groups (affected patients vs unaffected), we found no significant differences in bDMARD proportions. IL-1 inhibitors, IL-6 inhibitors, JAK inhibitors and belimumab-treated patients showed the lowest incidence of COVID-19 among adult patients with rheumatic diseases. We found no differences in sex or rheumatological disease between patients who tested positive for COVID-19 and patients who tested negative.Conclusions Overall, the use of biological disease-modifying antirheumatic drugs (bDMARDs) does not associate with severe manifestations of COVID-19. Patients with rheumatic disease diagnosed with COVID-19 were more likely to be receiving a higher dose of glucocorticoids and treatment with rituximab. IL-6 inhibitors may have a protective effect.