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Background: Patients with inflammatory arthritis (IA) are at increased risk of prosthetic joint infections (PJI), yet differentiating between septic and aseptic failure is a challenge. The aim of our systematic review is to evaluate synovial biomarkers and their efficacy at diagnosing PJI in patients with IA., Methods: A comprehensive literature search was performed in the following databases from inception to January 2018: Ovid MEDLINE, Ovid EMBASE, and the Cochrane Library. Searches across the databases retrieved 367 results. Two of 5 reviewers independently screened a total of 298 citations. Discrepancies were resolved by a third reviewer. Twenty articles fit our criteria, but due to methodological differences findings could not be pooled for meta-analysis. For 5 studies, raw data were provided, pooled, and used to derive optimal diagnostic cut points., Results: Our final analysis included 1861 non-IA patients, including 426 patients with PJI, and 90 IA patients of whom 26 had PJI. There was a significant difference among the 4 groups for serum C-reactive protein (CRP), erythrocyte sedimentation rate, and synovial CRP, polymorphonuclear neutrophil percent, white blood cells, interleukin (IL)-6, IL-8, and IL-1b. Polymorphonuclear neutrophil percent had the highest sensitivity (95.2%) and specificity (85.0%) to detect infections with an optimum threshold of 78%., Conclusion: While levels of synovial white blood cells, IL-6, IL-8, and serum CRP appear higher in patients with IA, there is overlap with those who are not infected. Further studies are needed to explore diagnostic tests that will better detect PJI in patients with IA., (Copyright © 2019 Elsevier Inc. All rights reserved.)

BackgroundA significant minority of patients receiving cardiac resynchronization therapy (CRT) remain nonresponsive to this intervention.ObjectiveThis study aimed to determine whether coronary sinus (CS) or baseline peripheral venous (PV) levels of established and emerging heart failure (HF) biomarkers are predictive of CRT outcomes.MethodsIn 73 patients (aged 68 ± 12 years; 83% men; ejection fraction 27% ± 7%) with CS and PV blood samples drawn simultaneously at the time of CRT device implantation, we measured amino-terminal pro-B-type natriuretic peptide (NT-proBNP), galectin-3 (gal-3), and soluble ST2 (sST2) levels. NT-proBNP concentrations >2000 pg/mL, gal-3 concentrations >25.9 ng/mL, and sST2 concentrations >35 ng/mL were considered positive on the basis of established PV cut points for identifying "high-risk" individuals with HF. CRT response was adjudicated by the HF Clinical Composite Score. A major adverse cardiovascular event (MACE) was defined as the composite end point of death, cardiac transplant, left ventricular assist device, and HF hospitalization at 2 years.ResultsNT-proBNP concentrations were 20% higher in the CS than in the periphery, while gal-3 and sST2 concentrations were 10% higher in the periphery than in the CS (all P < .001). There were 45% CRT nonresponders at 6 months and 16 (22%) patients with MACE. Triple-positive CS values yielded the highest specificity of 95% for predicting CRT nonresponse. Consistently, CS strategies identified patients at higher risk of developing MACE, with >11-fold adjusted increase for triple-positive CS patients compared to triple-negative patients (all P ≤ .04). PV strategies were not predictive of MACE.ConclusionOur findings suggest that CS sampling of HF biomarkers may be better than PV sampling for predicting CRT outcomes. Larger studies are needed to confirm our findings.

Background: Cardiorenal syndrome comprises a heterogeneous group of disorders characterized by acute or chronic cardiac and renal dysfunction.Objective: The purpose of this study was to determine the effect of cardiorenal status using a dual-marker strategy with amino-terminal pro-brain natriuretic peptide (NT-proBNP) and cystatin C on cardiac resynchronization therapy (CRT) outcomes.Methods: In 92 patients (age 66 ± 13 years; 80% male; left ventricular ejection fraction 26% ± 7%), NT-proBNP and cystatin C levels were measured at CRT implantation and at 1 month. NT-proBNP >1000 pg/mL and cystatin C >1 mg/L were considered high. Baseline cardiorenal patients were defined as having high NT-proBNP and cystatin C. At 1 month, CRT patients were categorized as (1) irreversible cardiorenal if cystatin C was persistently high; (2) progressive cardiorenal with transition from low to high cystatin C; (3) reversible cardiorenal with transition from high to low cystatin C; and (4) "normal" with stable low cystatin C. Outcomes were 6-month clinical and echocardiographic CRT response and 2 -year major adverse cardiovascular event (MACE).Results: Compared to patients with low NT-proBNP and cystatin C, cardiorenal patients had >9-fold increase risk of CRT nonresponse (odds ratio uncompensated 9.0; compensated 36.4; both P ≤.004) and >6-fold risk of MACE (hazard ratio uncompensated 8.5; P = .005). Compared to "normal" and reversible patients (referent), irreversible patients had a 9-fold increase for CRT nonresponse (odds ratio 9.1; P <.001) and had >4-fold risk of MACE (adjusted hazard ratio 5.1; P <.001). Irreversible patients were most likely echocardiographic CRT nonresponders.Conclusion: Cardiorenal status by NT-proBNP and cystatin C can identify high-risk CRT patients, and those with both elevated concentrations have worse prognosis. [ABSTRACT FROM AUTHOR]

Objective: In this study, we sought to refine histologic scoring of rheumatoid arthritis (RA) synovial tissue by training with gene expression data and machine learning. Methods: Twenty histologic features were assessed in 129 synovial tissue samples (n = 123 RA patients and n = 6 osteoarthritis [OA] patients). Consensus clustering was performed on gene expression data from a subset of 45 synovial samples. Support vector machine learning was used to predict gene expression subtypes, using histologic data as the input. Corresponding clinical data were compared across subtypes. Results: Consensus clustering of gene expression data revealed 3 distinct synovial subtypes, including a high inflammatory subtype characterized by extensive infiltration of leukocytes, a low inflammatory subtype characterized by enrichment in pathways including transforming growth factor β, glycoproteins, and neuronal genes, and a mixed subtype. Machine learning applied to histologic features, with gene expression subtypes serving as labels, generated an algorithm for the scoring of histologic features. Patients with the high inflammatory synovial subtype exhibited higher levels of markers of systemic inflammation and autoantibodies. C‐reactive protein (CRP) levels were significantly correlated with the severity of pain in the high inflammatory subgroup but not in the others. Conclusion: Gene expression analysis of RA and OA synovial tissue revealed 3 distinct synovial subtypes. These labels were used to generate a histologic scoring algorithm in which the histologic scores were found to be associated with parameters of systemic inflammation, including the erythrocyte sedimentation rate, CRP level, and autoantibody levels. Comparison of gene expression patterns to clinical features revealed a potentially clinically important distinction: mechanisms of pain may differ in patients with different synovial subtypes. [ABSTRACT FROM AUTHOR]

Objective The aim of the study was to determine the relationship of various thoracic fat depots with the presence and extent of coronary artery plaque and circulating biomarkers. Methods In 342 patients (52 ± 11 years, 61% male, BMI 29.1 ± 5.9 kg/m2) with coronary computed tomography (CT), angiography, we measured the fat volume in four thoracic depots (pericoronary, epicardial, periaortic, extracardiac), assessed coronary plaque, and determined the circulating levels of C-reactive protein, tumor necrosis factor alpha, plasminogen activator inhibitor-1, monocyte chemoattractant protein-1, and adiponectin. The extent of coronary plaque was classified into three groups: 0, 1−3, and >3 segments. Results Patients with plaque ( n =169, 49%) had higher volumes of all four fat depots as compared to patients without plaque (all P < 0.01), despite similar BMI ( P = 0.18). Extracardiac fat was most strongly correlated with BMI ( r = 0.45, P < 0.001), while pericoronary fat was least ( r = 0.21, P < 0.001). Only pericoronary fat remained associated with coronary plaque in adjusted analyses. Inflammatory biomarkers showed a positive correlation with pericoronary fat (all P < 0.0001), whereas adiponectin was not associated with this fat compartment ( P = 0.60) and showed a negative correlation with all other fat depots (all P < 0.001). Conclusions Pericoronary fat is independently associated with coronary artery disease (CAD). Its correlation with inflammatory biomarkers suggests that while systemic inflammation plays a role in the pathogenesis of CAD, there are additional local effects that may exist. [ABSTRACT FROM AUTHOR]

Aims Galectin-3 is a prognostic heart failure (HF) biomarker that may mediate cardiac fibrosis. We examined the value of serial galectin-3 measurement for prognosis and response to therapy in chronic HF. Methods and results A total of 151 subjects with LV systolic dysfunction (LVSD) were followed through 908 visits over 10 ± 3 months. The amount of time spent with a galectin-3 level ≤ 20.0 ng/mL and changes between baseline and subsequent values were considered across visits, and used to assess risk for adverse cardiovascular (CV) events and associations with LV remodelling. Medication effects on galectin-3 were examined. Median galectin-3 values at baseline, 3 months, and 6 months were higher in patients with CV events (21.7 vs. 18.4 ng/mL, P = 0.03; 21.7 vs. 16.5 ng/mL, P = 0.03; 23.2 vs. 16.0 ng/mL, P = 0.007). Galectin-3 concentration changed in 35.2% of subjects during study procedures; time spent at ≤ 20.0 ng/mL was significantly associated with a lower rate of CV events, independently predicted fewer CV events even adjusted for relevant variables including study allocation, NT-proBNP, and renal function [odds ratio (OR) = 0.90; P = 0.05], and predicted increase in LV ejection fraction (OR = 1.20; P = 0.04). Serial galectin-3 measurement at 6 months added prognostic value beyond the baseline level (P = 0.02). There were no significant effects of medications on galectin-3 levels. Conclusion In chronic HF due to LVSD, serial galectin-3 measurement adds incremental prognostic information and predicts LV remodelling. In this study, HF therapies had no clear effects on galectin-3 levels. [ABSTRACT FROM AUTHOR]

Background Despite the benefit of CRT in select patients with heart failure (HF), there remains significant need for predicting those at risk for adverse outcomes for this effective but costly therapy. CysC, an emerging marker of renal function, is predictive of worsening symptoms and mortality in patients with HF. This study assessed the utility of baseline and serial measures of cystatin C (CysC), compared to conventional creatinine-based measures of renal function (estimated glomerular filtration rate, eGFR), in predicting clinical outcomes following cardiac resynchronization therapy (CRT). Methods In 133 patients, we measured peripheral venous (PV) and coronary sinus (CS) CysC concentrations and peripheral creatinine levels at the time of CRT implant. Study endpoints included clinical response to CRT at 6 months and major adverse cardiac events (MACE) at 2 years. Results While all 3 renal metrics were predictive of MACE (all adjusted p ≤ 0.02), only CysC was associated with CRT non-response at 6 months (adjusted odds ratio 3.6, p = 0.02). CysC improved prediction of CRT non-response (p ≤ 0.003) in net reclassification index analysis compared to models utilizing standard renal metrics. Serial CysC > 1 mg/L was associated with 6-month CRT non-response and reduced 6-minute walk distance as well as 2-year MACE (all p ≤ 0.04). Conclusion In patients undergoing CRT, CysC demonstrated incremental benefit in the prediction of CRT non-response when compared to standard metrics of renal function. Baseline and serial measures of elevated CysC were predictive of CRT non-response and functional status at 6 months as well as long-term clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: With sacubitril/valsartan treatment, B-type natriuretic peptide (BNP) concentrations increase; it remains unclear whether change in BNP concentrations is similar across all assays for its measurement. Effects of sacubitril/valsartan on atrial natriuretic peptide (ANP) concentrations in patients are unknown. Lastly, the impact of neprilysin inhibition on mid-regional pro-ANP (MR-proANP), N-terminal pro-BNP (NT-proBNP), proBNP1-108, or C-type natriuretic peptide (CNP) is not well understood.Objectives: This study sought to examine the effects of sacubitril/valsartan on results from different natriuretic peptide assays.Methods: Twenty-three consecutive stable patients with heart failure and reduced ejection fraction were initiated and titrated on sacubitril/valsartan. Change in ANP, MR-proANP, BNP (using 5 assays), NT-proBNP (3 assays), proBNP1-108, and CNP were measured over 3 visits.Results: Average time to 3 follow-up visits was 22, 46, and 84 days. ANP rapidly and substantially increased with initiation and titration of sacubitril/valsartan, more than doubling by the first follow-up visit (+105.8%). Magnitude of ANP increase was greatest in those with concentrations above the median at baseline (+188%) compared with those with lower baseline concentrations (+44%); ANP increases were sustained. Treatment with sacubitril/valsartan led to inconsistent changes in BNP, which varied across methods assessed. Concentrations of MR-proANP, NT-proBNP, and proBNP1-108 variably declined after treatment; whereas CNP concentrations showed no consistent change.Conclusions: Initiation and titration of sacubitril/valsartan led to variable changes in concentrations of multiple natriuretic peptides. These results provide important insights into the effects of sacubitril/valsartan treatment on individual patient results, and further suggest the benefit of neprilysin inhibition may be partially mediated by increased ANP concentrations. [ABSTRACT FROM AUTHOR]