Serum calprotectin and joint ultrasound in the definition of disease relapse in non-systemic juvenile idiopathic arthritis: a prospective longitudinal study.

OBJECTIVES: The aim of our study was to investigate the role of serum calprotectin (SC) and muscle-skeletal ultrasound (MSUS) as predictive markers of relapse in patients with juvenile idiopathic arthritis (JIA). METHODS: Sixty non-systemic (ns) JIA patients in clinical remission were recruited to evaluate the risk of disease relapse. SC levels and JIA disease activity were assessed at every visit (3, 6, 12 and 18 months). Joint synovitis, characterised by both synovial effusion (SE) and synovial hyperplasia (SH), was measured by US score (sum of SE, SH, power Doppler and bone erosions) given to each examined joint and US ratio (US score/number of joints examined) at every visit. Associations of SC, US score and US ratio with relapse prevalence was studied longitudinally by using generalised estimating equations model. RESULTS: Thirty-one (51.6%) patients relapsed within 18 months. Patients with higher baseline US scores showed higher risk of relapse at 6 months (OR (95% confidence interval (CI)): 1.96 (1.09-3.52)). Additionally, patients with higher SC values at baseline showed higher risk of relapse at 18 months (1.66 (1.13-2.44)). Patients with higher baseline SC values showed an increased overall odds of relapse up to 18 months of follow-up (1.21 (1.08-1.36)). Furthermore, patients with higher US scores showed an increased overall odds of relapse up to 18 months of follow-up (1.96 (1.56-2.46)). Similarly, patients with higher US ratio showed an increased overall odds of relapse up to 18 months of follow-up (16.62 (7.17-38.54)). CONCLUSIONS: SC was able to identify JIA patients with unstable remission and increased risk of relapse. MSUS represents an interesting additional tool to the clinical evaluation, especially in predicting early relapse.

The Role of Serum Calprotectin in Defining Disease Outcomes in Non-Systemic Juvenile Idiopathic Arthritis: A Pilot Study.

Serum calprotectin (MRP8/14) is currently being studied as a promising biomarker of disease activity and outcome in patients with juvenile idiopathic arthritis (JIA) but the data in the literature are conflicting. The aim of our study was to investigate the potential role of serum calprotectin as biomarker of disease activity and flare/remission in a group of nsJIA patients during a follow-up period of 18 months. In this prospective longitudinal study, two groups of patients with ns-JIA (55 active patients and 56 patients in remission according to Wallace's criteria) and a control group (50 children) were recruited at baseline from January 2020 to September 2021. JIA patients were followed for up to 18 months at four timepoints: 3 months (T1), 6 months (T2), 12 months (T3) and 18 months (T4). At each timepoint, the following were recorded: JADAS27, blood counts, ESR, CRP, albumin, ferritin and serum calprotectin. To illustrate the performance of calprotectin, Kaplan-Meier curves were constructed from baseline to relapse/remission, dichotomizing patients at baseline in positive/negative on the basis progressive calprotectin cut-offs. Associations between baseline factors and relapse were determined using Cox regression models. Multivariate models were constructed to analyze the effect of covariates. Comparing baseline clinical and laboratory data of the three groups (active vs. inactive JIA vs. controls), only serum calprotectin reached statistical significance (active patients vs. inactive (p = 0.0016) and vs. controls (p = 0.0012)). In the inactive group, during the 18 months of follow up, 31 patients (55.3%) had a relapse. Comparing the baseline data of relapsers vs. non-relapsers, serum calprotectin showed higher levels (p = 0.001) in relapsers. In survival analysis, a log rank test showed significant differences of up to 12 ng/mL (p = 0.045). Multivariate Cox regression confirmed that only baseline calprotectin levels were independently associated with disease recurrence. In the active group, in the 12 months of follow-up, 19 patients (38%) entered remission of the disease. In addition, in this group, the only statistical difference at the baseline was the value of MPR8/14 (p = 0.0001). Log rank test showed significant differences up to 10 ng/mL (p = 0.003). In the multivariate Cox regression, serum calprotectin levels at baseline were independently associated with remission. In conclusion, our study would suggest a dual role for calprotectin in predicting future relapse and treatment response in patients with nsJIA, thus influencing therapeutic decisions and management of these patients during follow up.

Awake blood pressure variability, inflammatory markers and target organ damage in newly diagnosed hypertension.

Increased blood pressure (BP) may stimulate vascular inflammation, which may itself induce pathological arterial changes. BP variability has been associated with target-organ damage and future cardiovascular complications. We hypothesized that BP variability, as derived from ambulatory BP monitoring, is related to inflammatory markers in newly diagnosed hypertension. Systolic (S) and diastolic (D) BP variabilities were assessed as the SD of 24-h pressure recordings in a cohort of 190 recently (<6 months) diagnosed, untreated hypertensive subjects. Target organ damage, assessed by measuring the carotid artery intima-media thickness, left ventricular mass index, and microalbuminuria, was related to plasma high-sensitivity C-reactive protein (hsCRP) and soluble (s) E-selectin, an endothelium-specific molecule. The patients' age (mean+/-SD) was 53.0+/-8.5 years, and 59% were male. Multivariable analysis identified awake SBP variability (95% confidence interval [CI]: 0.002-0.042, p=0.034) as an independent correlate of hsCRP and awake SBP (95% CI: 0.003-0.014, p=0.003), awake SBP variability (95% CI: 0.003-0.035, p=0.018), and microalbuminuria (95% CI: 0.075-0.280, p=0.001) as independent correlates of sE-selectin. When patients were divided into low and high awake SBP variability groups, age (p=0.001), hsCRP (p=0.0001), and sE-selectin (p=0.005) were significantly different in the two groups. After adjusting for age, these differences remained significant (p=0.022 and p=0.001 for hsCRP and sE-selectin, respectively). In recently diagnosed hypertensive subjects, hsCRP and sE-selectin levels are related to awake SBP variability. High SBP variability is likely associated with vascular inflammation in newly diagnosed hypertension, independent of SBP. (Hypertens Res 2008; 31: 2137-2146).

Comparison of Serum Total Valproic Acid Levels and %CDT Values in Chronic Alcohol Addictive Patients in an Italian Clinic: A Retrospective Study.

BACKGROUND: Valproate is a broad-spectrum anticonvulsant that is effective in the treatment of tonic-clonic, myoclonic and absence seizures as well as in partial seizures as a second-line drug. It has been widely demonstrated in the literature that the effect of valproate on type-A γ-aminobutyric acid (GABA-A) receptors may reduce relapse to ethanol abuse. This retrospective study evaluated a 3-year period in which 42 patients from the Department of Alcoholism and Substance Abuse (DASA) were treated with valproate. OBJECTIVES: We compared different serum total valproic acid (VPA) concentrations, and the effectiveness of this drug in maintaining alcohol abstinence was evaluated by percentage of carbohydrate deficient transferrin (%CDT) values. METHOD: CDT is a biochemical marker used for identifying regular high alcohol consumption and monitoring abstinence in outpatients during treatment. Serum concentrations of valproate were divided into four groups: <10, 10-30, 31-50, and >50 µg/mL. RESULTS: This study shows that a mean serum total VPA concentration >30 µg/mL is more effective in maintaining alcohol abstinence than a lower one (p < 0.05). In this study, mean serum total VPA concentrations between 31 and 50 µg/mL showed the same effectiveness as higher ones (>50 µg/mL); in fact, there was no significant difference in mean %CDT values between these two groups (p > 0.05). After at least 12 months' treatment with valproate, mean platelet counts increased by 12 × 103/µL compared with baseline (254 ± 63 vs 242 × 103/µL, p > 0.05, respectively) in patients with mean serum total VPA levels <10 µg/mL; increased by 8 × 103/µL from baseline (253 ± 59 vs 245 × 103/µL, p > 0.05, respectively) in patients with levels between 10 and 30 µg/mL; decreased by 2 × 103/µL from baseline (265 ± 63 vs 267 × 103/µL, p > 0.05, respectively) in patients with levels between 31 and 50 µg/mL, and decreased by 48 × 103/µL from baseline (215 ± 56 vs 263 × 103/µL, p < 0.05, respectively) in patients with levels >50 µg/mL. CONCLUSION: A mean serum total concentration lower than the currently accepted therapeutic level (50-100 µg/mL) may have the same effectiveness in maintaining alcohol abstinence with a lower risk of presenting side effects.