Aims Inflammation and cardiac remodelling are common and synergistic pathways in heart failure (HF). Emerging biomarkers such as soluble suppression of tumorigenicity 2 (sST2) and growth differentiation factor-15 (GDF-15), which are linked to inflammation and fibrosis process, have been proposed as prognosis factors. However, their potential additive values remain poorly investigated. Methods and results Here, we aimed at evaluating inflammatory and remodelling biomarkers to predict both short-term and long-term mortality in a population with chronic HF in comparison with other classical clinical or biological markers (i.e. N terminal pro brain natriuretic peptide, hs-cTnT, C-reactive protein) alone or using meta-analysis global group in chronic HF risk score in a cohort of 182 patients followed during 80 months (interquartile range: 12.3-90.0). Proportional hazard assumption does not hold for sST2 and C-reactive protein, and follow-up was split into short term (less than 1 year), midterm (between 1 and 5 years), and long term (after 5 years). In univariate analysis, C-reactive protein and sST2 were predictive of short-term mortality but not of middle term and long term whereas GDF-15 was predictive of short and mid-term but not of long-term mortality. In a multivariate model after adjustment for meta-analysis global group in chronic HF score including the three markers, only sST2 was predictive of short-term mortality (P = 0.0225), and only GDF-15 was predictive of middle term mortality (P = 0.0375). None of the markers was predictive of long-term mortality. Conclusions Our results demonstrate that both sST2 and GDF-15 significantly improve the prognosis evaluation of HF patients and suggest that the value of GDF-15 is more sustained overtime and could predict middle term events.

The quantification of low abundant proteins in complex matrices by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) remains challenging. A measurement procedure based on optimized antibody-free sample preparation and isotope dilution coupled to LC-MS/MS was developed to quantify procalcitonin (PCT) in human serum at sub-microgram per liter level. A combination of sodium deoxycholate-assisted protein precipitation with acetonitrile, solid-phase extraction, and trypsin digestion assisted with Tween-20 enhanced the method sensitivity. Linearity was established through peptide-based calibration curves in the serum matrix (0.092-5.222 μg/L of PCT) with a good linear fit (R2 ≥ 0.999). Quality control materials spiked with known amounts of protein-based standards were used to evaluate the method's accuracy. The bias ranged from −2.6 to +4.3%, and the intra-day and inter-day coefficients of variations (CVs) were below 2.2% for peptide-based quality controls. A well-characterized correction factor was determined and applied to compensate for digestion incompleteness and material loss before the internal standards spike. Results with metrological traceability to the SI units were established using standard peptide of well-characterized purity determined by peptide impurity corrected amino acid analysis. The validated method enables accurate quantification of PCT in human serum at a limit of quantification down to 0.245 μg/L (bias −1.9%, precision 9.1%). The method was successfully applied to serum samples obtained from patients with sepsis. Interestingly, the PCT concentration reported implementing the isotope dilution LC-MS/MS method was twofold lower than the concentration provided by an immunoassay.

Objective To evaluate the association of baseline serum level of vitamin D (vitD) with disease activity, disability and radiographic damage over the first year in early rheumatoid arthritis (RA). Methods Among early arthritis patients included in the ESPOIR cohort, patients with early RA were evaluated. 25OH vitamin D2D3 level was measured at baseline. Baseline associations between vitD level and DAS28-ESR, Health Assessment Questionnaire Disability Index (HAQ-DI) and van der Heijde-modified total Sharp score (mTSS) were assessed. Bivariate analysis was used to assess the association between vitD level and radiographic progression (mTSS increased by ≥1 point) or disability (HAQ-DI ≥0.5) over 12 months. Forward stepwise multiple logistic regression was used to evaluate the independent association of baseline variables and outcomes. Results Among 813 patients with early arthritis, data for 645 RA patients were analyzed. VitD level was <10 ng/ml (deficiency, group 1), 10-30 ng/ml (low level, group 2) and ≥30 ng/ml (normal, group 3) for 114 (17.7%), 415 (64.6%), and 114 (17.7%) patients, respectively. At baseline, DAS28-ESR and HAQ-DI were higher with vitD deficiency as compared with groups 2 and 3 combined (p=0.007 and p=0.001, respectively) as was mean mTSS but not significantly (p=0.076). On multivariate analysis, baseline vitD deficiency was associated with HAQ-DI at 6 months (OR=1.70) and mTSS at 12 months (OR=1.76). Conclusion VitD deficiency was associated with more active and severe disease at baseline and may predict disability and radiographic progression over 1 year in early RA patients.

This prospective multicenter randomized comparative cross-over trial aimed at evaluating the influence of hemodialysis vs post-dilution hemodiafiltration with high-flux dialyzers in solute clearance and biocompatibility profile. 32 patients were sequentially dialyzed with Leoceed-21HX, Polypure-22S+, Rexsys-27H and VIE-21A. Primary outcome was β2-microglobulin removal. Secondary outcomes were (i) extraction of other uremic solutes (ii) parameters of inflammation and nutrition and (iii) comparative quantification of perdialytic albumin losses (using total ‘TDC’ vs partial ‘PDC’ collection of dialysate). Significant increases in removal rates of β2-microglobulin (84.7 ± 0.8 vs 71.6 ± 0.8 mg/L), myoglobin (65.9 ± 1.3 vs 38.6 ± 1.3 µg/L), free immunoglobulin light chains Kappa (74.9 ± 0.8 vs 55.6 ± 0.8 mg/L), β-trace protein (54.8 ± 1.3 vs 26.8 ± 1.4 mg/L) and orosomucoid (11.0 ± 1.1 vs 6.0 ± 1.1 g/L) but not myostatin (14.8 ± 1.5 vs 13.0 ± 1.5 ng/mL) were observed in HDF compared to HD when pooling all dialyzers. Rexsys and VIE-A use in both HD and HDF subgroups was associated to a better removal of middle/large-size molecules compared to Leoceed and Polypure, except β2-microglobulin for Rexsys. Inflammatory parameters were unchanged between dialyzers without any interaction with dialysis modality. Mean dialysate albumin loss was comparable between TDC and PDC (1.855 vs 1.826 g/session for TDC and PDC respectively). In addition, a significant difference in albumin loss was observed between dialyzers with the highest value (4.5 g/session) observed using Rexsys. Use of all dialyzers was associated with good removals of the large spectrum of uremic toxins tested and good biocompatibility profiles, with an additional gain in removal performances with HDF. Larger surface area, thinner wall and resultant very high ultrafiltration coefficient of Rexsys should be taken into account in its clear performance advantages.

Background Limited information exists on nursing home (NH) residents regarding BNT162b2 vaccine efficacy in preventing SARS‐CoV‐2 and severe COVID‐19, and its association with post‐vaccine humoral response. Methods 396 residents from seven NHs suffering a SARS‐CoV‐2 B.1.1.7 (VOC‐α) outbreak at least 14 days after a vaccine campaign were repeatedly tested using SARS‐CoV‐2 real‐time reverse‐transcriptase polymerase chain reaction on nasopharyngeal swab test (RT‐qPCR). SARS‐CoV‐2 receptor‐binding domain (RBD) of the S1 subunit (RBD‐IgG) was measured in all residents. Nucleocapsid antigenemia (N‐Ag) was measured in RT‐qPCR‐positive residents and serum neutralizing antibodies in vaccinated residents from one NH. Results The incidence of positive RT‐qPCR was lower in residents vaccinated by two doses (72/317; 22.7%) vs one dose (10/31; 32.3%) or non‐vaccinated residents (21/48; 43.7%; p < .01). COVID‐19–induced deaths were observed in 5 of the 48 non‐vaccinated residents (10.4%), in 2 of the 31 who had received one dose (6.4%), and in 3 of the 317 (0.9%) who had received two doses ( p = .0007). Severe symptoms were more common in infected non‐vaccinated residents (10/21; 47.6%) than in infected vaccinated residents (15/72; 21.0%; p = .002). Higher levels of RBD‐IgG ( n = 325) were associated with a lower SARS‐CoV‐2 incidence. No in vitro serum neutralization activity was found for RBD‐IgG levels below 1050 AU/ml. RBD‐IgG levels were inversely associated with N‐Ag levels, found as a risk factor of severe COVID‐19. Conclusions Two BNT162b2 doses are associated with a 48% reduction of SARS‐CoV‐2 incidence and a 91.3% reduction of death risk in residents from NHs facing a VOC‐α outbreak. Post‐vaccine RBD‐IgG levels correlate with BNT162b2 protection against SARS‐CoV‐2 B.1.1.7.