Objective Coronary artery disease (CAD) is the leading cause of excess deaths in RA. However, identification of features denoting those with CAD risk is lacking. The composition of circulating mononuclear cell (PBMC) subsets in RA cases differs markedly from healthy controls in extent of T-cell activation with clonal expansion and differentiation to memory effector status and presence of inflammatory monocytes. We sought to evaluate whether elevations in these subpopulations in RA denote those with increased risk for subclinical CAD, as measured by coronary artery calcium (CAC). Methods 72 RA patients underwent cardiac computed tomography to assess CAC. PBMC subsets were determined by multiparameter flow cytometry. Multivariable logistic regression was used to determine the associations between PBMC subpopulations and presence of CAC. Results 33% had CAC and exhibited significant increases of circulating CD4 T cell subsets denoting activation and differentiation to memory effector phenotypes. Analogous increases in CD8 T cell subsets, and intermediate CD14hiCD16+monocytes, were also present compared to those without CAC. The CD4 and CD8 T cell subset increases were highly intercorrelated, while increases in CD14hiCD16+monocytes were independent of the elevated CD4 subsets. After adjustment for relevant confounders, levels of CD4+CD56+CD57+ T cells and CD14hiCD16+monocytes remained associated with the presence of CAC. Conclusions These PBMC subsets are markers for CAC and suggest mechanisms of atherogenesis in RA may operate in part through their increases, raising further questions about the mechanisms underlying the presence of these subset alterations in RA and the potential for shared etiologic pathways between RA and CVD.

BACKGROUND:The average length of buprenorphine treatment for opioid use disorder is less than 6 months. OBJECTIVE: We conducted a systematic review to determine what factors were associated with longer retention in buprenorphine treatment. DESIGN: We searched Medline, Embase, and Cochrane Database of Systematic Reviews in February 2018. Articles were restricted to randomized controlled trials on human subjects, written in English, which contained ≥ 24 weeks of objective data on retention in buprenorphine treatment. MAIN MEASURES:We assessed whether dose of buprenorphine, treatment setting, or co-administration of behavioral therapy was associated with retention rates. KEY RESULTS: Over 14,000 articles were identified. Thirteen articles (describing 9 studies) met inclusion criteria. Measures of retention varied widely. Three studies compared doses of buprenorphine between 1 and 8 mg and showed significantly higher rates of retention with higher doses (p values < 0.01). All other studies utilized buprenorphine doses between 8 and 24 mg daily, without comparison. No study found a significant difference in r e t e n t i o n b e t w e e n b u p r e n o r p h i n e a l o n e a n d buprenorphine plus behavioral therapy (p values > 0.05). Initiating buprenorphine while hospitalized or within criminal justice settings prior to outpatient treatment programs was significantly associated with retention in buprenorphine treatment (p values < 0.01 respectively). CONCLUSIONS: Setting of treatment initiation and a higher buprenorphine dose are associated with improved long-term treatment retention. More objective data on buprenorphine treatment programs are needed, including a standardized approach to defining retention in buprenorphine treatment programs. REGISTRATION: This review was registered with PROS-PERO (#CRD42019120336) in March 2019.

Objective. Adipose tissue macrophages (ATMs) are a potent source of inflammatory cytokines, with profound effects on adipose tissue function, yet their potential role in rheumatoid arthritis (RA) pathobiology is largely unstudied. Methods. Periumbilical subcutaneous adipose tissue was obtained from 36 RA patients and 22 non-RA controls frequency matched on demographics and body mass index. Samples were stained for the macrophage marker CD68, and the average proportions of ATMs, crown-like structures (periadipocyte aggregates of 3 or more ATMs), and fibrosis were compared between groups. Results. The adjusted proportion of ATMs among all nucleated cells was 76% higher in RA than in non-RA samples (37.7 versus 21.3%, respectively; P < 0.001), and the adjusted average number of crown-like structures was more than 1.5-fold higher in the RA group than in controls (0.58 versus 0.23 crown-like structure/high-power field, respectively; P = 0.001). ATMs were significantly more abundant in early RA and in those with anti-cyclic citrullinated peptide seropositivity. Users of methotrexate, leflunomide, and tumor necrosis factor inhibitors had a significantly lower proportion of ATMs compared with nonusers. Crown-like structures were significantly higher in patients with rheumatoid factor seropositivity and in those with C-reactive protein levels ≥10 mg/liter, and significantly lower among those treated with statins. Linear ATMs were significantly associated with whole-body insulin resistance, but not with serum lipids. Conclusion. ATMs and crown-like structures were more abundant in RA patients and were associated with systemic inflammation, autoimmunity, and whole-body insulin resistance, suggesting possible contributions to the RA disease process. Lower levels of ATMs and crown-like structures associated with specific RA treatments suggest that adipose tissue inflammation may be ameliorated by immunomodulation.

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