Objective To estimate atherosclerosis progression and identify influencing factors in rheumatoid arthritis (RA). Methods We used carotid ultrasound to measure intima-media thickness (IMT) in RA patients, and ascertained cardiovascular (CV) risk factors, inflammation markers and medications. A second ultrasound was performed approximately 3 years later. We calculated the progression rate by subtracting the baseline from the follow-up IMT, divided by the time between the two scans. We used logistic regression to identify baseline factors predictive of rapid progression. We tested for interactions of erythrocyte sedimentation rate (ESR) with CV risk factors and medication use. Results Results were available for 487 RA patients. The mean (SD) common carotid IMT at baseline was 0.571 mm (0.151). After a mean of 2.8 years, the IMT increased by 0.050 mm (0.055), p≤0.001, a progression rate of 0.018 mm/year (95% CI 0.016 to 0.020). Baseline factors associated with rapid progression included the number of CV risk factors (OR 1.27 per risk factor, 95% CI 1.01 to 1.61), and the ESR (OR 1.12 per 10 mm/h, 95% CI 1.02 to 1.23). The ESR×CV risk factor and ESR×medication product terms were significant, suggesting these variables modify the association between the ESR and IMT progression. Conclusions Systemic inflammation and CV risk factors were associated with rapid IMT progression. CV risk factors may modify the role of systemic inflammation in determining IMT progression over time. Methotrexate and antitumour necrosis factor agents may influence IMT progression by reducing the effect of the systemic inflammation on the IMT.

Objective To examine the association of socioeconomic status (SES) and delays in DMARD treatment with clinical measures in rheumatoid arthritis (RA) patients. Methods RA patients were recruited from rheumatology clinics. We assessed SES based on education, occupation and income and divided patients into tertiles. The time from RA symptom onset to DMARD initiation (DMARD lag) was determined by self-report of the two dates, and distance to the rheumatologist (Distance) was obtained from Google Maps. We examined disease activity, determined by DAS28ESR, joint damage, determined from hand radiographs by Sharp scores, and physical disability, determined by the Modified Health Assessment Questionnaire (MHAQ). We used linear regression models to examine the relationship between clinical measures and SES, Distance, and DMARD lag. Results We recruited 1,209 RA patients, 1159 of whom had received DMARD treatment. Average ± SD DMARD lag was 6.9 ± 9.0 years. On average, patients with lower SES waited 8.5 ± 10.2 years after onset of RA symptoms to begin DMARD treatment, compared to those in middle and upper SES tertiles who waited 6.1 ± 7.9 years (P=0.002) and 6.1 ± 8.6 years (P=0.009), respectively. Each year of delayed treatment was associated with a DAS28ESR increase of 0.02 (P≤0.001), a Sharp score increase of 1.33 (P≤0.001) and MHAQ score increase of 0.01 (P≤0.001). Conclusion Low SES was associated with delay in DMARD initiation, and both were independently associated with worse clinical measures in RA. Strategies to reduce treatment delay in low SES RA patients are needed.

The metabolic machinery for the biosynthesis of Coenzyme A (CoA) from exogenous pantothenic acid (Vitamin B5) has long been considered as an excellent target for the development of selective antimicrobials. Earlier studies in the human malaria parasite Plasmodium falciparum have shown that pantothenate analogs interfere with pantothenate phosphorylation and block asexual blood stage development. Although two eukaryotic-type putative pantothenate kinase genes (PanK1 and PanK2) have been identified in all malaria parasite species, their role in the development of Plasmodium life cycle stages remains unknown. Here we report on the genetic characterization of PanK1 and PanK2 in P. yoelii. We show that P. yoelii parasites lacking either PanK1 or PanK2 undergo normal asexual stages development and sexual stages differentiation, however they are severely deficient in ookinete, oocyst and sporozoite formation inside the mosquito vector. Quantitative transcriptional analyses in wild-type and knockout parasites demonstrate an important role for these genes in the regulation of expression of other CoA biosynthesis genes. Together, our data provide the first genetic evidence for the importance of the early steps of pantothenate utilization in the regulation of CoA biosynthesis and malaria parasite transmission to Anopheles mosquitoes.

No abstract

Background Cytokines seen in severe COVID-19 are associated with proliferation, differentiation, and survival of plasma cells. Plasma cells are not routinely found in peripheral blood, though may produce virus-neutralizing antibodies in COVID-19 later in the course of an infection. Methods Using the Johns Hopkins COVID-19 Precision Medicine Analytics Platform Registry, we identified hospitalized adult patients with confirmed SARS-CoV-2 infection and stratified by presence of plasma cells and WHO disease severity. To identify plasma cells, we employed a sensitive flow cytometric screening method for highly fluorescent lymphocytes and confirmed these microscopically. Cox regression models were used to evaluate time to death and time to clinical improvement by the presence of plasma cells in patients with severe disease. Results Of 2,301 hospitalized patients with confirmed infection, 371 had plasma cells identified. Patients with plasma cells were more likely to have severe disease, though 86.6% developed plasma cells after onset of severe disease. In patients with severe disease, after adjusting for age, sex, BMI, race and other covariates associated with disease severity, patients with plasma cells had a reduced hazard of death (aHR: 0.57; 95%CI: 0.38 to 0.87; p-value: 0.008). There was no significant association with the presence of plasma cells and time to clinical improvement. Conclusions Patients with severe disease who have detectable plasma cells in the peripheral blood have improved mortality despite adjusting for known covariates associated with disease severity in COVID-19. Further investigation is warranted to understand the role of plasma cells in the immune response to COVID-19.