Study Design Retrospective chart analysis of 199 individuals aged 18-80 years scheduled for lumbar spine surgery. Objective The purpose of this study was to quantify changes in muscle cross sectional area (CSA) and fat signal fraction (FSF) with age in men and women with lumbar spine pathology and compare them to published normative data. Summary of Background Data Pathological changes in lumbar paraspinal muscle are often confounded by age-related decline in muscle size (CSA) and quality (fatty infiltration). Individuals with pathology have been shown to have decreased CSA and fatty infiltration of both the multifidus and erector spinae muscles, but the magnitude of these changes in the context of normal aging is unknown. Methods Individuals aged 18-80 years who were scheduled for lumbar surgery for diagnoses associated with lumbar spine pain or pathology were included. Muscle CSA and FSF of the multifidus and erector spinae were measured from preoperative T2-weighted magnetic resonance images at the L4 level. Univariate and multiple linear regression analyses were performed for each outcome using age and gender as predictor variables. Statistical comparisons of univariate regression parameters (slope and intercept) to published normative data were also performed. Results There was no change in CSA with age in either gender (p>0.05), but women had lower CSA's than men in both muscles (p<0.0001). There was an increase in FSF with age in erector spinae and multifidus muscles in both genders (p<0.0001). Multifidus FSF values were higher in women with lumbar spine pathology than published values for healthy controls (p=0.03), and slopes tended to be steeper with pathology for both muscles in women (p<0.08) but not in men (p>0.31). Conclusions Lumbar muscle fat content, but not CSA changes with age in individuals with pathology. In women, this increase is more profound than age-related increases in healthy individuals.

Objective We investigated whether rheumatoid arthritis (RA)-related autoantibodies were associated with systemic inflammation in a prospective cohort of first-degree relatives (FDRs) of RA probands, a population without RA but at increased risk for its future development. Methods We studied 44 autoantibody positive FDRs, of whom 29 were rheumatoid factor (RF) positive, 25 were positive for the high risk autoantibody profile (HRP), that is, positive for anti-cyclic citrullinated peptide and/or for at least two RF IgM, IgG or IgA isotypes, and nine FDRs who were positive for both; and 62 FDRs who were never autoantibody positive. Twenty-five cytokines/chemokines were measured using a bead-based assay in serum. As a comprehensive measure of inflammation, we calculated a Cytokine Score by summing all cytokine/chemokine levels, weighted by their regression coefficients for RA-autoantibody association. We compared C-reactive protein, individual cytokines/chemokines and Cytokine Score to the outcomes: positivity for RF and for the HRP using logistic regression. Results Adjusting for age, sex, ethnicity and ever smoking, the Cytokine Score and levels of IL-6 and IL-9 were associated with both RF and HRP. IL-2, granulocyte macrophage-colony stimulating factor (GM-CSF), and interferon (IFN)-γ were associated with HRP only. Associations between the Cytokine Score and RF and HRP positivity were replicated in an independent military personnel cohort. Conclusions In first-degree relatives of patients with RA, RA-related autoimmunity is associated with inflammation, as evidenced by associations with multiple cytokines and chemokines.

Objective To compare commonly-available tests for antibodies to citrullinated protein antigens (ACPAs) for diagnostic accuracy and assay agreement in established rheumatoid arthritis (RA) and subjects at elevated risk for RA. Methods ELISA testing for anti-cyclic citrullinated peptide (anti-CCP) antibodies was performed using CCP2 (Axis-Shield) and CCP3.1 (IgA/IgG INOVA) in the following subjects: 1) probands with established RA (N=340) from the Studies of the Etiology of RA (SERA), 2) first degree relatives (FDRs) without RA (family members of SERA RA probands; N=681), 3) Department of Defense Serum Repository (DoDSR) RA cases with pre-diagnosis samples (N=83; 47/83 also had post-diagnosis samples), and 4) blood-donor and DoDSR controls (N=283). Results In established RA, CCP2 was more specific (99.2% vs. 93.1%, p<0.01), but less sensitive (58.7% vs. 67.4%, p=0.01) than CCP3.1, with specificity of CCP3.1 increasing to 97.2% if levels ≥3 times the standard cut-off level were considered. In all subjects, at standard cut-off levels, CCP3.1 positivity was more prevalent. In DoDSR cases, CCP2 was more specific than CCP3.1 for a future diagnosis of RA, and higher CCP levels trended towards greater specificity for disease onset within 2 years. At standard cut-off levels, assay agreement was good in established RA (kappa=0.76), but poor in FDRs without inflammatory arthritis (kappa=0.25). Conclusion Anti-CCP assays differ to an extent that may be meaningful in diagnosing RA in patients with inflammatory arthritis, and in evaluating the natural history of RA development in subjects at-risk for future RA. Mechanisms underlying these differences in test performance need further investigation.

Serum potassium concentration ≥5.0 mEq/L was associated with all-cause mortality, CVD death, and non-CVD death in community-living individuals; associations were stronger in diuretic users. Whether maintenance of potassium within the normal range may improve clinical outcomes requires future study.

STRUCTURED ABSTRACT Objectives We aimed to determine the correlation between coronary artery calcium (CAC) scores on 3mm ECG-gated computed tomography (CT) scans and standard 6mm chest CT scans, and to compare relative strength of associations of CAC on each scan type with mortality risk. Background Coronary artery calcification predicts cardiovascular disease (CVD) and all-cause mortality, and is typically measured on ECG-gated 3mm CT scans. Patients undergo standard 6mm chest CTs for various clinical indications much more frequently, but CAC is not usually quantified. To better understand the usefulness of standard chest CTs to quantify CAC, we conducted a case-control study among persons who had both scan types. Methods Between 2000–03, 4,544 community-living individuals self- or physician-referred for “whole body” CT scans, had 3mm ECG-gated CTs and standard 6mm chest CTs, and were followed for mortality through 2009. In this nested case-control study, we identified 157 deaths and 494 controls frequency matched (1:3) on age and gender. The Agatston method quantified CAC on both scan types. Unconditional logistic regression determined associations with mortality, accounting for CVD risk factors. Results Participants were 68±11 years old and 63% male. The Spearman correlation of CAC scores between the two scan types was 0.93 (p<0.001); median CAC scores were lower on 6mm CTs compared to 3mm CTs (22 vs.104 Agatston units, p<0.001). Adjusted for traditional CVD risk factors, each SD higher CAC score on 6mm CTs was associated with 50% higher odds of death (OR=1.5; 1.2–1.9), similar to 50% higher odds on the 3mm ECG-gated CTs (OR=1.5, 1.1–1.9). Conclusions CAC scores on standard 6mm chest CTs are strongly correlated with 3mm ECG-gated CTs and similarly predict mortality in community-living individuals. Chest CTs performed for other clinical indications may provide an untapped resource to garner CVD risk information without additional radiation exposure or expense.