Anna Eder

Background: We aim to evaluate the impact of prepregnancy overweight on treatment modalities of Gestational Diabetes Mellitus (GDM). We assessed the association of increased pregravid Body Mass Index (BMI) with dosing of basal and rapid acting insulin as well as pregnancy outcome. Methods: We included 509 gestational diabetic women (normal weight: 200, overweight: 157, obese: 152), attending the pregnancy outpatient clinic at the Department of Obstetrics and Gynecology, Medical University of Vienna, in this retrospective study. We used a prospectively compiled database to assess patient characteristics, treatment approaches - particularly maximum doses of basal and rapid acting insulin or metformin - and pregnancy outcome. Results: Increased BMI was associated with the need of glucose lowering medication (odds ratio (OR): 1.08 for the increase of 1 kg/m² BMI, 95%CI 1.05-1.11, p<0.001). Mothers with pregestational obesity received the highest amount of insulin. Metformin was more often used in patients with obesity who also required higher daily doses. Maternal BMI was associated with increased risk of cesarean section (OR 1.04, 95%CI 1.01-1.07, p<0.001) and delivering large for gestational age offspring (OR 1.09, 95%CI 1.04-1.13, p<0.001). Birthweight percentiles were highest in patients with obesity who required glucose lowering therapy. Conclusions: Treatment modalities and outcome in GDM pregnancies are closely related to the extent of maternal BMI. Patients with obesity required glucose lowering medication more often and were at higher risk of adverse pregnancy outcomes. It is crucial to further explore the underlying pathophysiologic mechanisms to optimize clinical management and individual treatment approaches.

BACKGROUND: In COPD, the course of the disease including morbidity and mortality is strongly associated with severe exacerbations. The current GOLD recommendations emphasize blood eosinophil counts as a marker for responsiveness to inhaled corticosteroids (ICS). Retrospective analyses from randomized clinical trials indicate a favorable response to systemic corticosteroids in exacerbated COPD patients with blood eosinophils > 2%, however data outside clinical trials are scarce. PATIENTS AND METHODS: We retrospectively evaluated data from 1007 cases of patients who were admitted to the University Medical Center Marburg between 01/2013 and 12/2018. All patients had been diagnosed with an acute exacerbation of COPD (ICD-10 J44.0/J44.1). Our analysis was based on a subgroup of 417 patients in whom a full blood cell count was obtained at the day of admission. Patients were predominantly male (63.3%), had a median age of 74 years (IQR 65 years - 83 years) and a median FEV1 of 1.03 l (42.6% predicted). We compared the hospital length of stay and other outcome parameters using established thresholds for the eosinophil blood cell count (100 and 300 eosinophils/μl and 2%). RESULTS: Patients with low eosinophils (< 2%, <100 cells/μl) had a longer median time in hospital (length of hospital stay - LOS) as compared to patients with high eosinophils (< 2%: 9.31 vs. ≥2%:7 days, and < 100/μl: 10 vs. 100-300/μl: 8 vs. > 300/μl: 7 days). The median CRP was higher in patients with low eosinophils as compared to the other groups (< 2%: 22.7 vs. ≥2%: 9 mg/dl and < 100: 25 vs. 100-300: 13.5 vs. > 300: 7.1 mg/dl). Time to re-hospitalization or time to death did not differ between strata of eosinophils. Sensitivity analysis in a subgroup of patients in which pneumonia was excluded by chest x-ray did not significantly alter the results. CONCLUSION: The results support the hypothesis that patients with severe COPD exacerbations and elevated blood eosinophil counts respond better to systemic corticosteroid treatment than patients with a non-eosinophilic exacerbation.

To assess the humoral response to vaccination against SARS-CoV-2 in patients with rheumatoid arthritis treated with methotrexate (MTX). In total, 142 fully vaccinated individuals were included at 6 ± 1 weeks after their second vaccination [BioNTech/Pfizer (70.4%), AstraZeneca (20.4%), and Moderna (9.2%)]. The primary goal was to assess the humoral immune response as measured by titres of neutralising antibodies against the S1 antigen of SARS-CoV-2. In a cross-sectional, single-centre study, titres were compared between patient subgroups with (n = 80) and without (n = 62) methotrexate exposure. MTX patients showed a significantly reduced humoral response to vaccination in the oldest patient subgroup (> 70 years: P = 0.038), whereas titres of neutralising antibodies were not significantly different between MTX and non-MTX patients in patients less than 70 years of age (< 56 years: P = 0.234; 56-70 years: P = 0.446). In patients > 70 years, non-MTX patients showed a maximum immune response in 76.5% of cases, whereas this percentage was reduced to 53.7% in study participants on MTX medication (effect size d = 0.21). Older age in patients with rheumatoid arthritis in combination with methotrexate results in a significantly reduced humoral response after vaccination against SARS-CoV-2. Our data underline the importance of age regarding the humoral response and may support the temporary cessation of methotrexate, particularly in elderly patients in the context of vaccination against SARS-CoV-2.

Abstract Objective Several studies on the immunogenicity of vaccination against coronavirus disease 2019 (COVID-19) in patients with immune-mediated inflammatory diseases have evaluated the influence of DMARDs. The aim of the work presented here was to compare the humoral vaccine response after two vaccinations between patients with RA undergoing TNF inhibitor therapy and healthy controls. Methods We assessed the humoral immune response, as measured by titres of neutralizing antibodies against the S1 antigen of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in patients with RA and anti-TNF treatment vs. controls without immunomodulatory medication. One hundred and seven fully vaccinated individuals were included at 6 ± 1 weeks after the second vaccination [BioNTech/Pfizer (72.9%), AstraZeneca (17.8%) and Moderna (9.3%)]. Immune responses in terms of antibody titres were compared between both subgroups with (n = 45) and without (n = 62) exposure to anti-TNF medication. The comparison was performed as a cross-sectional, single-centre study approach using non-parametric tests for central tendency. Results Anti-TNF medication produced a significantly impaired humoral immune response to vaccination against COVID-19. The maximum immune response was detected in 77.4% of control patients, whereas this decreased to 62.2% in participants treated with TNF inhibitors (P = 0.045; effect size, d = 0.194). Patients on combination treatment (anti-TNF medication and MTX, 17 of 45 subjects in the treatment group) did not differ significantly regarding humoral immune response compared with patients on monotherapy with TNF inhibitors only (P = 0.214). Conclusion TNF inhibitors significantly reduce the humoral response following dual vaccination against COVID-19 in patients with RA.