Ultrasound halo count in the diferential diagnosis of atherosclerosis and large vessel giant cell arteritis

Objective To determine the diagnostic discriminant validity between large vessel giant cell arteritis (LV-GCA) and atherosclerosis using ultrasound (US) intima-media thickness (IMT) measurements. Methods We included 44 patients with LV-GCA and 42 with high-risk atherosclerosis. US examinations of the axillary, subclavian, and common carotid arteries (CCA) were systematically performed using a MylabX8 system (Genoa, Italy) with a 4–15-MHz probe. IMT≥1 mm was accepted as pathological. Results The LV-GCA cohort included 24 females and 20 males with a mean age of 72.8±7.6 years. The atherosclero‑ sis group included 25 males and 17 females with a mean age of 70.8±6.5 years. The mean IMT values of all arteries included were signifcantly higher in LV-GCA than in atherosclerosis. Among LV-GCA patients, IMT≥1 mm was seen in 31 axillary, 30 subclavian, and 28 CCA. In the atherosclerotic cohort, 17 (38.6%) had IMT≥1 mm with axillary involve‑ ment in 2 patients, subclavian in 3 patients, carotid distal in 14 patients (5 bilateral), and isolated carotid proximal afectation in 1 case. A cutof point greater than 1 pathological vessel in the summative count of axillary and sub‑ clavian arteries or at least 3 vessels in the count of six vessels, including CCA, showed a precision upper 95% for GCA diagnosis. Conclusion The IMT is higher in LV-GCA than in atherosclerosis. The proposed US halo count achieves an accuracy of>95% for the diferential diagnosis between LV-GCA and atherosclerosis. The axillary and subclavian arteries have higher discriminatory power, while carotid involvement is less specifc in the diferential diagnosi

Clinical predictors of multiple failure to biological therapy in patients with rheumatoid arthritis.

Biological therapies have improved the clinical course and quality of life of rheumatoid arthritis (RA) patients. Despite the availability and effectiveness of these treatments, some patients experience multiple failures to biologic disease-modifying antirheumatic drugs (bDMARDs), constituting a particular challenge to clinicians. This study aims to determine the percentage of rheumatoid arthritis (RA) patients who fail to respond to subsequent bDMARDs, describe their characteristics, and identify specific baseline and early features during the first bDMARD as possible predictors of consecutive multiple bDMARD failure. This is a longitudinal study involving RA patients from the prospective biological cohort drawn from the La Paz University Hospital RA Registry (RA-Paz), starting a bDMARD during the years 2000 to 2019. Patients who presented insufficient response (due to primary or secondary inefficacy) to at least three bDMARDs or two bDMARDs with different mechanism of action were considered multi-refractory (MR-patients). Patients who achieved low disease activity or remission (by DAS-28) with the first bDMARD and maintained this over a follow-up period of at least 5 years were considered non-refractory (NR-patients). A total of 41 out of 402 (10%) patients were MR-patients and 71 (18%) NR-patients. In the multivariate analysis, the presence of erosions, younger age, higher baseline DAS-28 and mostly achieving delta-DAS < 1.2 after 6 months of the first bDMARD (OR 11.12; 95% CI 3.34-26.82) were independently associated with being MR-patients to bDMARDs. In our cohort, 10% of patients with RA were observed to have multi-refractoriness to bDMARDs. This study supports the contention that younger patients with erosive disease and especially the early absence of clinical response to the first bDMARDs are predictors of multi-refractoriness to consecutive biologics. Hence, patients with these characteristics should be monitored more closely and may benefit from personalized treatments.This work was supported by the Fundación Española de Reumatología (FER) and Instituto de Salud Carlos III (ISCIII), Ministry of Health, Spain (Juan Rodés research contract to MNN).S

Increased frequency of circulating CD19+CD24hiCD38hi B cells with regulatory capacity in patients with Ankylosing spondylitis (AS) naïve for biological agents.

Our objective was to study the frequency of circulating CD19+CD24hiCD38hi B cells (Breg) in AS patients. To this end, peripheral blood was drawn from AS patients naïve for TNF blockers (AS/nb) (n = 42) and healthy controls (HC) (n = 42). Six patients donated blood for a second time, 6 months after initiating treatment with anti-TNFα drugs. After isolation by Ficoll-Hypaque, PBMCs were stained with antibodies to CD3, CD4, CD19, CD24, and CD38, and examined by cytometry. For functional studies, total CD19+ B cells were isolated from PBMCs of 3 HC by magnetical sorting. Breg-depleted CD19+ B cells were obtained after CD19+CD24hiCD38hi B cells were removed from total CD19+ cells by cytometry. Total CD19+ B cells or Breg-depleted CD19+ B cells were established in culture and stimulated through their BCR. Secretion of IFNγ was determined by ELISA in culture supernatants. When compared with HC, AS/nb patients demonstrated a significantly increased frequency of Breg cells, which was independent of disease activity. Anti-TNFα drugs induced a significant reduction of circulating Breg numbers, which were no longer elevated after six months of treatment. Functional in vitro studies showed that the secretion of IFNγ was significantly higher in Breg-depleted as compared with total CD19+ B cells, indicating that Breg can downmodulate B cell pro-inflammatory cytokine secretion. In summary, an increased frequency of circulating CD19+CD24hiCD38hi B cells is observed in AS/nb patients, that is not related with disease activity; anti-TNFα drugs are able to downmodulate circulating Breg numbers in AS

Numbers of circulating CD19+CD24^hiCD38^hi B cells in AS patients naïve for TNF blockers (AS/nb).

<p>PBMCs isolated from the peripheral blood of AS/nb patients (n = 42) and from age and gender-matched healthy controls (HC) (n = 42) were stained with fluorochrome-labeled antibodies against cell surface markers and examined by flow cytometry. AS/nb patients showed an increased proportion and absolute numbers of circulating CD19+CD24^hiCD38^hi B cells. A. Representative dot plots demonstrate CD24 and CD38 expression in cells gated for CD19. B, C. Frequency (B) and absolute numbers (C) of circulating CD19+CD24^hiCD38^hi B cells in HC and AS/nb patients. Bars represent the median and interquartile range. *p<0.01.</p

Suppressive capacity of CD19+CD24^hiCD38^hi B cells in healthy subjects.

<p>Total CD19+ or B cells depleted of CD19+CD24^hiCD38^hi cells (Breg-depleted CD19+ B cells), isolated from the peripheral blood of three healthy controls (HC), were established in culture, and stimulated with anti-IgM+IgG. Secretion of IFNγ was determined in culture supernatants by sandwich ELISA at 2, 5 or 7 days. Bar graphs represent the mean and SEM for IFNγ concentrations of 3 independent experiments.</p

Clinical characteristics of AS/nb patients.

<p>Clinical characteristics of AS/nb patients.</p

Treatment with anti-TNF agents is associated with a significant reduction of circulating CD19+CD24^hiCD38^hi B cell numbers in AS patients.

<p>A. Frequency of CD19+CD24^hiCD38^hi B cells in six AS patients before and six months after initiating treatment with anti-TNFα agents, and in their 6 age and gender-matched healthy controls at the basal and 6 month study. (*p<0.05) B. CRP, calprotectin and ASDAS-CRP values in these 6 AS/nb patients before and six months after initiating treatment with anti-TNFα. (*p<0.05)</p