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The aim of the present study was, first, to evaluate the prognostic value of mid-regional proadrenomedullin (proADM) in emergency department (ED) patients with a diagnosis of community acquired pneumonia (CAP) and, second, to analyze the added value of proADM as a risk stratification tool in comparison with other biomarkers and clinical severity scores. We evaluated proADM, C-reactive protein and procalcitonin, along with the Pneumonia Severity Index (PSI) score in consecutive CAP patients. Ability to predict 30-day mortality was assessed using receiver operating characteristic curve analysis, logistic regression, and reclassification metrics for all patients and for patients with high PSI scores. Primary outcome was death within 30 days after ED admission. One hundred nine patients were included (median age [interquartile range] 71 [27] years). Nine patients died within 30 days. A significant correlation between proADM and PSI was found (ρ = 0.584, P < .001). PSI and proADM levels were significantly predictive of risk of death. In patients with PSI class IV and V (score >90), proADM levels significantly predicted risk of death (OR [95% CI], 4.681 (1.661-20.221), P = .012) whereas PSI score did not (P = .122). ROC(AUC) (area under the receiver operating characteristic curve) was higher for proADM than for PSI score (ROC(AUC) [95% CI], 0.810 [0.654-0.965] and 0.669 [0.445-0.893] respectively). Reclassification analysis revealed that combination of PSI and proADM allows a better risk assessment than PSI alone (P = .001). MR-proADM may be helpful in individual risk stratification of CAP patients with a high PSI score in the ED, allowing to a better identification of patients at risk of death. [ABSTRACT FROM AUTHOR]

Objective: To describe lipid levels in antiretroviral (ARV)-naïve HIV-infected Ivorian children and assess their evolution after ARV-treatment initiation. Methods: Lipid concentrations were assessed at baseline and at least 6 months later in 93 children. Fifty-six children initiated ARV treatment at baseline, and 37 remained untreated. Results: At baseline, 65, 92 and 84% of the children had low levels of total cholesterol, HDL and APOA1, respectively, whereas 75 and 70% had triglycerides and APOB levels in the normal range. At baseline, low level of HDL cholesterol and high level of triglycerides were associated with high viral load and low levels of CD4 cell count. Levels of total, HDL cholesterol and APOA1 increased over time, and treatment was associated with a higher increase whereas levels of triglycerides and APOB decreased in treated children and remained stable in untreated group. Conclusions: The initiation of antiretroviral treatment was associated with a normalization of the infection-related lipid profile. [ABSTRACT FROM AUTHOR]

The aim of this prospective cohort study was to evaluate the effects of lipid lowering agent (LLA) intake on cognitive function in 6,830 community-dwelling elderly persons. Cognitive performance (global cognitive functioning, visual memory, verbal fluency, psychomotor speed, and executive function), clinical diagnosis of dementia, and fibrate and statin use, were evaluated at baseline, and 2, 4, and 7 year follow-up. Multivariate Cox models were stratified by gender and adjusted for sociodemographic characteristics, mental and physical health including vascular risk factors, and genetic vulnerability (apolipoprotein E and cholesteryl ester transfer protein). For women but not men, fibrate use was specifically associated with an increased risk over 7 years of decline in visual memory only (HR = 1.29, 95% CI = 1.09-1.54, p = 0.004), and did not increase risk for incident dementia. This association was independent of genetic vulnerability related to apolipoprotein E and cholesteryl exchange transfer protein polymorphisms and occurred only in women with higher low density lipoprotein (LDL)-cholesterol levels and treated with fibrate (HR = 1.39, 95% CI = 1.08-1.79, p = 0.01) and not in those with lower LDL-cholesterol levels irrespective of fibrate treatment. For both genders, no significant associations were found between statins (irrespective of their lipophilicity) and either cognitive decline or dementia incidence. This prospective study, adjusting for multiple confounders, found no evidence that LLA given in late life reduced the risk of cognitive decline and dementia, but did raise the possibility that women with treatment-resistant high LDL-cholesterol may be at increased risk of decline in visual memory. [ABSTRACT FROM AUTHOR]

Background: Reactive oxygen species production increases during aging, whereas protective mechanisms such as heat shock proteins (HSPs) or antioxidant capacity are depressed. Physical activity has been hypothesized to provide protection against oxidative damage during aging, but results remain controversial. This study aimed to investigate the effect of different levels of physical activity during aging on Hsp72 expression and systemic oxidative stress at rest and in response to maximal exercise.Methods: Plasma antioxidant capacity (Trolox equivalent antioxidant capacity, TEAC), thiobarbituric acid-reactive species (TBARS), advanced oxidized proteins products (AOPP), and Hsp72 expression in leukocytes were measured before and after maximal exercise testing in 32 elderly persons (aged 73.2 years), who were assigned to two different groups depending on their level of physical activity during the past 12 months (OLow = moderate to low level; OHigh = higher level).Results: The OHigh group showed higher aerobic fitness and TEAC (both representing 120% of OLow values) as well as lower oxidative damage (50% of OLow values) and Hsp72 expression. Exercise led to a lower increase in oxidative damage in the OHigh group. Aerobic fitness was positively correlated with TEAC and negatively with lipid peroxidation (TBARS). Hsp72 expression was negatively correlated with TEAC but positively correlated with TBARS levels.Conclusions: The key finding of this study is that, in people aged 60 to 90 years, long-term high level of physical activity preserved antioxidant capacity and limited oxidative damage accumulation. It also downregulated Hsp72 expression, an adaptation potentially resulting from lower levels of oxidative damage. [ABSTRACT FROM AUTHOR]

Oxidative stress has been implicated in the development of Alzheimer's disease (AD). Consequently, antioxidant therapies including Vitamin E (VitE) supplementation for both prevention and treatment of neurodegenerative diseases currently appears to be a promising avenue of research. The aim of the present study was to examine the relationship between AD and the ApoE phenotype, lipid parameters and VitE levels in a large cohort of elderly subjects. No absolute deficit was observed in plasma VitE levels. However in AD, ApoE4 is not associated with an increase in total cholesterol (TC) and VitE levels. Moreover, our results suggest that oxidative stress-induced injury and protection by VitE in AD are related to the ApoE phenotype. Our study strongly supports the hypothesis of an impairment of lipophilic antioxidant delivery to neuronal cells in AD leading to a tissular antioxidant deficiency which could facilitate oxidative stress. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background : Acute heart failure (AHF) represents a leading cause of unscheduled hospital stays, frequent rehospitalisations, and mortality worldwide. The aim of our study was to develop a bedside prognostic tool, a multivariable predictive risk score, that is useful in daily practice, thus providing an early prognostic evaluation at admission and an accurate risk stratification after discharge in patients with AHF. Methods : This study is a subanalysis of the STADE HF study, which is a single-centre, prospective, randomised controlled trial enrolling 123 patients admitted to hospital for AHF. Here, 117 patients were included in the analysis, due to data exhaustivity. Regression analysis was performed to determine predictive variables for one-year mortality and/or rehospitalisation after discharge. Results : During the first year after discharge, 23 patients died. After modellisation, the variables considered to be of prognostic relevance in terms of mortality were (1) non-ischaemic aetiology of HF, (2) elevated creatinine levels at admission, (3) moderate/severe mitral regurgitation, and (4) prior HF hospitalisation. We designed a linear model based on these four independent predictive variables, and it showed a good ability to score and predict patient mortality with an AUC of 0.84 (95%CI: 0.76-0.92), thus denoting a high discriminative ability. A risk score equation was developed. During the first year after discharge, we observed as well that 41 patients died or were rehospitalised; hence, while searching for a model that could predict worsening health conditions (i.e., death and/or rehospitalisation), only two predictive variables were identified: non-ischaemic HF aetiology and previous HF hospitalisation (also included in the one-year mortality model). This second modellisation showed a more discrete discriminative ability with an AUC of 0.67 (95% C.I. 0.59-0.77). Conclusions : The proposed risk score and model, based on readily available predictive variables, are promising and useful tools to assess, respectively, the one-year mortality risk and the one-year mortality and/or rehospitalisations in patients hospitalised for AHF and to assist clinicians in the management of patients with HF aiming at improving their prognosis.

Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: The authors report the relevance of using a point of care test (Helge ® ) for free hemoglobin determination and concordance of the values the with Cobas ® 8000 and spectrophotometer methods. Results: The within-run of the point of care test was <3%. Good correlations among the three methods were observed and an acceptable concordance for hemolysis index values from 50 mg/dl. An excellent agreement between the Cobas 8000 and the spectrophotometer was found. Conclusion: Automated methods represent methods of choice for free hemoglobin determination. An advantage of the Helge system is that it can be applied to samples experiencing a delay in evaluation due to the long distance between the collection site and the central laboratory. Another advantage is its use at the bedside, in the monitoring of extracorporeal membrane oxygenation patients.

Background and Aims: The dialysate magnesium (Mg) concentration is a major determinant of Mg balance in hemodialysis. This study aimed to assess the systemic variations of total (tMg) and ionized Mg (iMg) during a dialysis session using acetate or citrate fluids and 0.5 or 0.75 mM Mg., Materials and Methods: 134 patients in maintenance hemodialysis were assigned to a dialysis session with 4 different dialysates: acetate fluid with 0.5 mM Mg (1) or 0.75 mM Mg (2), citrate fluid with 0.5 mM Mg (3) or 0.75 mM Mg (4). Ionized form was measured by direct ion-selective electrode., Results: A Mg loss was observed in both acetate (0.12 and 0.08 mmol/L) and citrate (0.13 and 0.14 mmol/L for tMg and iMg, respectively) fluid groups containing 0.5 mM Mg. The use of acetate and citrate dialysates with 0.75 mM Mg led to a significant median intra-dialytic increase of 0.15 and 0.08 mmol/L for tMg, respectively. A significant augmentation in iMg concentration with acetate (0.11 mmol/L) but not with citrate dialysate (0.02 mmol/L) was observed., Conclusion: While a dialysate Mg concentration at 0.5 mM leads to a negative balance, increasing the concentration to 0.75 mM significantly raises post-dialysis circulating Mg. Monitoring of iMg should allow a personalized prescription in dialysate Mg., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: Blood microsampling, particularly dried blood spots (DBSs), is an attractive minimally-invasive approach that is well suited for home sampling and predictive medicine associated with longitudinal follow-up of the elderly. However, in vitro diagnostic quantification of biomarkers from DBS poses a major challenge. Clinical mass spectrometry can reliably quantify blood proteins in various research projects. Our goal here was to use mass spectrometry of DBS in a real-world clinical setting and compared it to the standard immunoassay method. We also sought to correlate DBS mass spectrometry measurements with clinical indices., Methods: A clinical trial of diagnostic equivalence was conducted to compare conventional venous samples quantified by immunoassay and DBSs quantified by mass spectrometry in an elderly population. We assayed three protein biomarkers of nutritional and inflammatory status: prealbumin (transthyretin), C-reactive protein, and transferrin., Results: The analysis of DBSs showed satisfactory variability and low detection limits. Statistical analysis confirmed that the two methods give comparable results at clinical levels of accuracy. In conclusion, we demonstrated, in a real-life setting, that DBSs can be used to measure prealbumin, CRP and transferrin, which are commonly used markers of nutritional status and inflammation in the elderly. However, there was no correlation with patient frailty for these proteins., Conclusions: Early detection and regular monitoring of nutritional and inflammatory problems using DBS appear to be clinically feasible. This could help resolve major public health challenges in the elderly for whom frailty leads to serious risks of health complications., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Faced with the pandemic viral circulation of SARS-CoV-2, healthcare establishments have had to maintain an effective screening strategy in order to prevent nosocomial clusters. Automated antigenic tests appear to be a reliable and complementary alternative to RT-PCR (reverse transcriptase polymerase chain reaction) in order to optimize patient care in the emergency department. We report our experience of the deployment of the LumiraDx antigen tests on the LumiraDx platform, as well as the comparison of these tests' results with the RT-PCR results on a population of patients sampled in the emergency department.

Background and Aims: Mobility and migration flows are growing from different countries of the world to European countries, including France and in particular the Mediterranean basin. This study aimed to investigate the presence of hemoglobin (Hb) variants in outpatients/inpatients of the Montpellier Hospital (France) in whom an HbA1c assay had been performed and for which the country of birth had been informed., Methods: This is a retrospective study from January 2016 to December 2020 based on all high-performance liquid chromatography (HPLC) chromatograms (Tosoh Bioscience HLC-723G8) having an alarm of suspected Hb variant during HbA1c measurement. The corresponding samples were systematically sent to the hematology laboratory for confirmation and identification of Hb variant. Patient's medical history, clinical and demographic data were extracted from each medical chart. Statistical analyses were performed using XLSTAT® software, version 2016.06.35661., Results: Three hundred sixty-three patients were confirmed with Hb variant exhibiting 17 different Hb profiles, highlighting the pivotal role of glycated hemoglobin (HbA1c) as a detection step. The prevalence of Hb variant in this southern French population was 0.71%, with the highest frequency for the beta-globin variants ( n  = 342/363; i.e., 94.2%), including the most common: S, C, E, and D in 200/342 (58.5%), 83/342 (24.3%), 29/342 (8.5%), and 11/342 (3.2%), respectively. Among patients with Hb variants, almost half (165/363; i.e., 45.4%) were born in the African continent with a predominance for Morocco (32/165; i.e., 19.3%) and Algeria (29/165; i.e., 17.5%)., Conclusion: HbA1c assay is a useful tool to detect Hb variants. Hemoglobinopathies are a public health issue in the current French population which is a multiethnic society. Despite the monocentric nature of our study, we note a high frequency of Hb variants in the south of France, which underlines the importance of screening for Hb variants in the whole population., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Blood microsampling combined with large panels of clinically relevant tests are of major interest for the development of home sampling and predictive medicine. The aim of the study was to demonstrate the practicality and medical utility of microsamples quantification using mass spectrometry (MS) in a clinical setting by comparing two types of microsamples for multiplex MS protein detection. In a clinical trial based on elderly population, we compared 2 µL of plasma to dried blood spot (DBS) with a clinical quantitative multiplex MS approach. The analysis of the microsamples allowed the quantification of 62 proteins with satisfactory analytical performances. A total of 48 proteins were significantly correlated between microsampling plasma and DBS ( p < 0.0001). The quantification of 62 blood proteins allowed us to stratify patients according to their pathophysiological status. Apolipoproteins D and E were the best biomarker link to IADL (instrumental activities of daily living) score in microsampling plasma as well as in DBS. It is, thus, possible to detect multiple blood proteins from micro-samples in compliance with clinical requirements and this allows, for example, to monitor the nutritional or inflammatory status of patients. The implementation of this type of analysis opens new perspectives in the field of diagnosis, monitoring and risk assessment for personalized medicine approaches.

Many Point-of-Care devices have been released over the past decade. However, data regarding their analytical performances in real-world situations remains scarce. Herein, we aimed to assess the analytical performances of the i-STAT Alinity system. We conducted an analytical performances study with the i-STAT Alinity device using cartridges CG4+ (pH, Pco2, Po2, lactate, bicarbonate and base excess); CHEM8+ (Na, K, Cl, ionized Ca, urea, creatinine, glucose, hematocrit and hemoglobin) and PT/INR (prothrombin time and international normalized ratio). We assessed the imprecision and compared the results to those obtained on existing instruments in the central laboratory. We found that the within-lab coefficients of variation (CV) were very low (<2%) or low (2−5%), except for creatinine and PT (CV = 5.2% and CV = 6.3%, respectively). For almost all the parameters, the results were strongly (R2 = 90−95%) or very strongly (R2 > 95%) correlated with those of the existing laboratory instruments, and the biases were very low (<2%) or low (2−5%). However, correlations of the PT and INR measurements with existing instruments were lower (R2 = 86.0% and 89.7%), and biases in the Po2 (7.9%), creatinine (5.4%) and PT (−6.6%) measurements were higher. The i-STAT Alinity appeared as a convenient device for measurements of numerous parameters. However, clinicians should interpret Po2, creatinine and PT results with caution.

Tubular injury is the main cause of acute kidney injury (AKI) in critically ill COVID-19 patients. Proximal tubular dysfunction (PTD) and changes in urinary biomarkers, such as NGAL, TIMP-2, and IGFBP7 product ([TIMP-2]•[IGFBP7]), could precede AKI. We conducted a prospective cohort study from 2020/03/09 to 2020/05/03, which consecutively included all COVID-19 patients who had at least one urinalysis, to assess the incidence of PTD and AKI, and the effectiveness of PTD, NGAL, and [TIMP-2]•[IGFBP7] in AKI and persistent AKI prediction using the area under the receiver operating characteristic curves (AUCs), Kaplan-Meier methodology (log-rank tests), and Cox models. Among the 60 patients admitted to the ICU with proven COVID-19 (median age: 63-year-old (interquartile range: IQR, 55-74), 45 males (75%), median simplified acute physiology score (SAPS) II: 34 (IQR, 22-47) and median BMI: 25.7 kg/m 2 (IQR, 23.3-30.8)) analyzed, PTD was diagnosed in 29 patients (48%), AKI in 33 (55%) and persistent AKI in 20 (33%). Urinary NGAL had the highest AUC for AKI prediction: 0.635 (95%CI: 0.491-0.779) and persistent AKI prediction: 0.681 (95%CI: 0.535-0.826), as compared to PTD and [TIMP-2]•[IGFBP7] (AUCs <0.6). AKI was independently associated with higher SAPSII (HR = 1.04, 95%CI: 1.01-1.06, p  = 0.005) and BMI (HR = 1.07, 95%CI: 1.00-1.14, p  = 0.04) and persistent AKI with higher SAPSII (HR = 1.03, 95%CI: 1.00-1.06, p  = 0.048) and nephrotoxic drug use (HR = 3.88, 95%CI: 1.20-12.5, p  = 0.02). In conclusion, in critically ill COVID-19 patients, the incidence of PTD and AKI was relatively high. NGAL was the best urinary biomarker for predicting AKI, but only clinical severity was independently associated with its occurrence.

Objectives: Aldosterone and renin determinations play an important role in the etiological diagnosis of secondary hypertension. The analytical performances of new aldosterone and renin immunoassays on the Lumipulse G600II ® system (Fujierbio) were investigated and compared with those of the iSYS ® system (IDS) on patients concerned by medical investigations in a context of suspected or proven Primary aldosteronism., Methods: By using the Lumipulse ® G Aldosterone and Renin assays we performed imprecision study, linearity and method comparison (n=107). Accuracy of this new renin assay was tested using the International Standard (WHO IS 68/356). We also assessed the equivalence of the different samples types (n=29)., Results: The imprecision evaluation showed all CVs <3% and <6% for Lumipulse ® G Aldosterone and Renin assays respectively. The linearity was excellent over the clinical range and the comparison with the iSYS ® assays (n=79) showed a strong correlation (R 2 =1) despite a slight tendency to underestimation (bias of -17.53 pg/mL or 48.56 pmol/L for aldosterone and -15.395 pg/mL for renin). Moreover, the contingency studies based on diagnostic criteria showed that Lumipulse ® G results lead to the same clinical diagnosis that iSYS ® results. A clear correlation was obtained between EDTA and heparin plasma as well as with the serum for all range of measures., Conclusions: The Lumipulse ® G Aldosterone and Renin assays present performances compatible with a routine use in medical laboratories. The precise quantification in the low range can be of interest in some clinical contexts especially standing/laying tests. However, the standardisation against the WHO International Standard Renin would be advisable., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Fibroblast growth factor 19 (FGF19) is a hormone with pleiotropic metabolic functions, leading to ongoing development of analogues for treatment of metabolic disorders. On the other hand, FGF19 is overexpressed in a sub-group of hepatocellular carcinoma (HCC) patients and has oncogenic properties. It is therefore crucial to precisely define FGF19 effects, notably in the context of chronic exposure to elevated concentrations of the hormone. Here, we used hydrodynamic gene transfer to generate a transgenic mouse model with long-term FGF19 hepatic overexpression. We describe a novel effect of FGF19, namely the stimulation of water intake. This phenotype, lasting at least over a 6-month period, depends on signaling in the central nervous system and is independent of FGF21, although it mimics some of its features. We further show that HCC patients with high levels of circulating FGF19 have a reduced natremia, indicating dipsogenic features. The present study provides evidence of a new activity of FGF19, which could be clinically relevant in the context of FGF19 overexpressing cancers and in the course of treatment of metabolic disorders by FGF19 analogues., (Copyright © 2022 The Authors. Published by Elsevier GmbH.. All rights reserved.)

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., (© 2021 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Objectives: The two-fold aim of this study was: (i) to determine the effects of undernutrition on the myokines in patients with restrictive anorexia nervosa (AN) and (ii) to examine the potential link between myokines and bone parameters., Methods: In this study, 42 young women with restrictive AN and 42 age-matched controls (CON) (mean age, 18.5 ± 4.2 years and 18.6 ± 4.2 years, respectively) were enrolled. aBMD and body composition were determined with DXA. Resting energy expenditure (REEm), a marker of energy status, was indirectly assessed by calorimetry. Bone turnover markers and myokines (follistatin, myostatin and irisin) were concomitantly evaluated., Results: AN patients presented low aBMD at all bone sites. REEm, bone formation markers, myostatin and IGF-1 were significantly lower, whereas the bone resorption marker and follistatin were higher in AN compared with controls. No difference was observed between groups for irisin levels. When the whole population was studied, among myokines, only myostatin was positively correlated with aBMD at all bone sites. However, multiple regression analyses showed that in the AN group, the independent variables for aBMD were principally amenorrhoea duration, lean tissue mass (LTM) and procollagen type I N-terminal propeptide (PINP). For CON, the independent variables for aBMD were principally LTM, age and PINP. Whatever the group analysed, none of the myokines appeared as explicative independent variables of aBMD., Conclusion: This study demonstrated that despite the altered myokine levels in patients with AN, their direct effect on aBMD loss and bone turnover alteration seems limited in comparison with other well-known disease-related factors such as oestrogen deprivation.

Objectives: Methotrexate requires therapeutic drug monitoring in oncology because of narrow therapeutic index, especially the metabolite 7-hydroxymethotrexate exhibits nephrotoxicity. The goal of this study was to evaluate different assays and their impact on clinical decisions., Methods: Following routine measurement with Abbott TDxFLx® assay (MTX-TDX), 62 samples were analysed on Architect®i1000 (MTX-ARCHI), Xpand® (ARK/XPND), Indiko® (ARK/INDI), and HPLC (MTX-HPLC) as the reference method. The influence of 7-hydroxymethotrexate was explored on ARK reagent to document the cause of the observed bias. ROC curves were built to study the impact of the method on the discharge thresholds for the patients at three levels., Results: Total imprecision was below 2.60% for the methotrexate-ARCHI and close to 10% for both ARK assays for plasma pools. The correlation coefficients were 0.93, 0.93, 0.89 and 0.95, the Bland-Altman difference plot revealed a bias of 0.075, 0.037, 0.049 and -0.002, and the number of results exceeding the TE criteria of 0.1 µM was 17 (27%), 13 (21%), 15 (24%) and 15 (24%) for MTX-TDX, ARK/INDI, ARK/XPND and MTX-ARCHI, respectively. Cross reactivity with 7-hydroxymethotrexate was between 1 and 9%. Overestimation of methotrexate concentration was between -4% and +32%. The most robust clinical level was found to be the highest level (0.2 µM) with ROC curves., Conclusions: The authors found the best results for imprecision with chemiluminescent microparticle immunoassay method on methotrexate-ARCHI, with bias below to the RICOS recommendations and best correlation to the reference method. Impact on the threshold values for clinical decision need to be clearly exposed to clinicians.

Objectives: Human growth hormone (hGH) provocation test is an essential tool to assess growth hormone deficiency (GHD) in children and young adults. It is important to have a robust method to determine the hGH peak of stimulation. This work aimed to compare three common automated immunoassays for hGH quantification and to ascertain whether there are still result-related differences which can impact clinical decision., Methods: We analyzed the GH provocation test for 39 young subjects from pediatric department of Montpellier hospital, admitted for suspicion of growth hormone deficiency. The full range of measurements as well as the peak level of serum GH were compared using three automated immunoassays on three different immunoanalyzers: IDS-hGH on iSYS, LIAISON-hGH on Liaison XL and Elecsys ROCHE-hGH, on COBAS 8000., Results: A good correlation was obtained between methods for all measurements ( r 2 >0.99) by using Passing-Bablok regression analysis. Bland-Altman analysis showed the best agreement between IDS-hGH and LIAISON-hGH systems (bias=-14.5%) compared to Elecsys ROCHE-hGH (bias=28.3%). When considering stratification of the study population and a unique cutoff, there were some discrepancies in interpretation of the results especially concerning the more recent Elecsys ROCHE-hGH assay. Nevertheless, when the adequate cutoff for each method was taken into account results were well correlated for all systems., Conclusions: A cutoff for Elecsys Roche-hGH method was established to better explain the results. Clinician must be aware of the use of assay-specific cutoff to correctly integrate the results of GH tests in the GHD diagnosis., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Discharging patients home as quickly as possible, or gaining the ability to eliminate a serious event is a goal requested by clinicians in the emergency department (ED). For this, risk scores, taking into account co-morbidities, have been established. The aim of our study consists to evaluate in patients with chest pain admitted in ED the risk stratification obtained with clinico-biological risk scores (CCS, GRACE score, TIMI score and HEART score) using Ortho hs-cTnI assay (Ortho Clinical Diagnostics, Illkirch, France) on the Vitros 3600® instrument or Roche hs-cTnT assay on the Cobas8000/e801® module (Roche diagnostics, Meylan, France), with comparison to hs-cTn-only strategy. Prognostic performances were evaluated according to AMI with or without STEMI, and deaths during hospitalization., Methods: Patients admitted to the ED presenting chest pain or symptoms suggesting of acute coronary syndrome (ACS) were included. Hs-cTnT was performed on a Roche hs-cTnT assay on the Cobas8000/e801® module using a fifth-generation assay and was used for the clinical diagnosis. In addition, hs-cTnI was tested using Ortho hs-cTnI assay on the Vitros 3600® analyzer. Retrospectively, we collected the variables needed for each score in clinical records. Our endpoint were occurrence of AMI in patients with chest pain after presentation to the ED and all cause death during the hospitalization., Results: We enrolled 160 patients with suspected ACS. The adjudicated diagnosis was AMI in 37 patients (with 9 STEMI and 28 NSTEMI), cardiac pathologies in 57 patients and other causes in 66 patients. The majority of patients were classified at high risk for each risk scores (from 42% to 68%) whatever the considered hs-cTn assay, except for TIMI score. Cohen's kappa agreements with GRACE, TIMI and HEART scores were excellent between Roche hs-cTnT vs Ortho hs-cTnI. The AUC of the HEART score was highest for both hs-cTn to predict AMI, NSTEMI or death, with no statistical difference according to the hs-cTn (p = NS) assay used. NRI analysis confirmed the interest of HEART score which improved individual risk prediction for AMI (or NSTEMI) and death., Conclusion: In view of our results, the decision aids using only biological variables (hs-cTn-only strategy and CCS) would seem more effective for rule-out AMI whereas bioclinical risk scores could better identify patients at low and high risk for mortality. In consequence, risk scores taking in account comorbidities, appear necessary to determine the outcome and thus to adapt the therapeutic options. It is interesting to note that the HEART score could be useful for the rule out AMI but also for the risk prediction as confirmed by the NRI., (Copyright © 2021. Published by Elsevier B.V.)

Palm olein (PO) and olive oil (OO) are widely consumed in the world. PO is considered harmful to health, whereas OO is considered healthy. The aim of the study was to compare the effects of consumption of these oils on antioxidant status and inflammation in rats. This was an experimental study in male wistar rats fed a diet containing 30% of each oil. Rats had free access to food and water. After being fed for 12 weeks, animals were sacrificed and liver and aortic blood were collected. Plasma was used for the determination of interleukin-6 (IL-6) and oxidative stress parameters (Superoxide dismutase -SOD; Gluthation peroxidase - GPx; Thiobarbituric acid reactive substances - TBARS; Thiol groups and isoprostane). The inflammation and oxidative stress status as well as the expression of several genes/proteins were also analyzed in liver homogenate. No significant differences were observed between PO and OO in plasma and liver levels of the studied inflammation and oxidative stress parameters. This study showed that the consumption of PO induces an antioxidant status superimposable to that of OO.   Key words : Palm olein - Olive oil - Oxidative stress - Inflammation - High fat diet.

Inflammatory processes are deeply involved in ischemia-reperfusion injuries (IRI) and ventricular remodelling (VR) after a ST-segment elevation myocardial infarction (STEMI). They are associated with clinical adverse events (heart failure and cardiovascular death) adding damage to the myocardium after reperfusion. Moreover, acute myocardial infarction (AMI) induces a local sympathetic denervation leading to electrical instability and arrythmia. Colchicine, a well-known alkaloid with direct anti-inflammatory effects, was shown to reduce the myocardial necrosis size and limit the VR. In a recent proof of concept study, colchicine appears to prevent sympathetic denervation in a mice model of ischemia/reperfusion, but not in the necrosis or in the border zone areas. The Colchicine to Prevent Sympathetic Denervation after an AMI study (COLD-MI) is an ongoing, confirmative, prospective, monocentre, randomized, open-label trial. The COLD-MI trial aims to evaluate the intensity of sympathetic denervation after AMI and its potential modulation due to low dose colchicine. Sympathetic denervation will be noninvasively evaluated using single-photon emission computed tomography (SPECT). After a first episode of STEMI (Initial TIMI flow ≤ 1) and primary percutaneous coronary intervention (PPCI), patients will be randomized (n = 56) in a 1:1 ratio to either receive colchicine or not for 30 days. The primary end point will be the percentage of myocardial denervation measured by 123I-metaiodobenzylguanidine (123I-MIBG) SPECT at a 6-month follow-up. The main secondary end points will be basic ECG parameters (QRS duration, corrected QT) and HRV parameters from a 24 hour-recording Holter at 1- and 6-months follow-up. Results from this study will contribute to a better understanding of the cardioprotective effect of colchicine after AMI. The present study describes the rationale, design, and methods of the trial.

Half of the patients with heart failure (HF) have preserved ejection fraction (HFpEF). To date, there are no specific markers to distinguish this subgroup. The main objective of this work was to stratify HF patients using current biochemical markers coupled with clinical data. The cohort study included HFpEF ( n = 24) and heart failure with reduced ejection fraction (HFrEF) ( n = 34) patients as usually considered in clinical practice based on cardiac imaging (EF ≥ 50% for HFpEF; EF < 50% for HFrEF). Routine blood tests consisted of measuring biomarkers of renal and heart functions, inflammation, and iron metabolism. A multi-test approach and analysis of peripheral blood samples aimed to establish a computerized Machine Learning strategy to provide a blood signature to distinguish HFpEF and HFrEF. Based on logistic regression, demographic characteristics and clinical biomarkers showed no statistical significance to differentiate the HFpEF and HFrEF patient subgroups. Hence a multivariate factorial discriminant analysis, performed blindly using the data set, allowed us to stratify the two HF groups. Consequently, a Machine Learning (ML) strategy was developed using the same variables in a genetic algorithm approach. ML provided very encouraging explorative results when considering the small size of the samples applied. The accuracy and the sensitivity were high for both validation and test groups (69% and 100%, 64% and 75%, respectively). Sensitivity was 100% for the validation and 75% for the test group, whereas specificity was 44% and 55% for the validation and test groups because of the small number of samples. Lastly, the precision was acceptable, with 58% in the validation and 60% in the test group. Combining biochemical and clinical markers is an excellent entry to develop a computer classification tool to diagnose HFpEF. This translational approach is a springboard for improving new personalized treatment methods and identifying "high-yield" populations for clinical trials.

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., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Recently, Ortho Clinical Diagnostics have launched a high sensitivity cardiac troponin I assay adapted on Vitros3600 / 5600. We aimed at evaluating the analytical and clinical performances using the 0/3-hour algorithm, of the Ortho hs-cTnI assay on the Vitros 3600® (Ortho Clinical Diagnostics, Illkirch, France) analyzer with comparison to Roche hs-cTnT assay on the Cobas8000/e801® module (Roche diagnostics, Meylan, France) and the Abbott STAT hs-cTnI assay on the Alinity i® (Abbott, Rungis, France) analyzer., Methods: Imprecision studies, linearity, limit of detection, and the interference to hemolysis were performed for Ortho hs-cTnI assay. The concordance study was based on results of troponin obtained from 160 patients with chest pain to the emergency department. Testing was performed simultaneously measuring the Roche hs-cTnT and the Ortho hs-cTnI, then on remaining sample the concentration of Abbott hs-cTnI (n = 150). We applied the 0/3h algorithm to rule out/rule in, in acute myocardial infarction., Results: Analytical performances were acceptable and in accordance with manufacturer's data. For late presenters 100, 92.8 and 88.8% patients could be rule-out with Roche, Ortho and Abbott assay, respectively with one NSTEMI missed with both hs-TnI assays. Applying the hs-cTn cut-offs from 0/3-hour algorithm, 107 (66.8%) could be rule out with Roche hs-cTnT with no AMI missed (sensitivity 100% [95%CI: 90.5 to 100] and NPV 100%); 89 with Ortho hs-cTnI (sensitivity 97.3% [95%CI: 85.8-99.9] and NPV 98.8% [95%CI:92.7-99.8]); and 61 with Abbott hs-cTnI (sensitivity 97% [95%CI: 84.2-99.9] and NPV 98.4% [95%CI: 89.8-99.7]). For rule-in, 23.7% (n = 37) from the total population would be designated in this group, with a specificity of 86.9% (95%CI: 79.7-92.4) and PPV of 69.8% (95%CI: 59.4-78.5) vs specificity of 72.3% (95%CI:63.5-80.0) and PPV of 51.4% (95%CI: 44.1-58.2)with Roche hs-cTnT vs Ortho hs-cTnI respectively; and with Abbott, 33 patients had constitued this group with a specificity of 52.1% (95%CI:42.7-61.4) and PPV of 36.4% (95%CI: 32.0-41.0)., Conclusion: In conclusion, according to ESC guidelines, our results indicate that the Ortho hs-cTnI assay for the Vitros 3600 instrument is a method that may be used in the clinical practice using 0/3-hour algorithm., (Copyright © 2021. Published by Elsevier B.V.)

Point of care testing makes it possible to obtain results in an extremely short time. Recently, radiometer has expanded the panel of tests available on its ABL90 FLEX PLUS blood gas analyzer (ABL90) by adding urea and creatinine. The aim of this study was to verify the performance of these new parameters. This included assessment of imprecision, linearity, accuracy by comparison with central laboratory standard assays and interferences. In addition, clinical utility in a dialysis center was evaluated. Within-lab coefficients of variation were close to 2%. The mean and limits of agreement (mean ± 1.96 SD) of the difference between ABL90 and Roche enzymatic assays on cobas 8000 were 0.5 (from -1.4 to 2.3) mmol/L and -0.9 (from -19.5 to 17.8) µmol/L for urea and creatinine, respectively. The ABL90 enzymatic urea and creatinine assays met the acceptance criteria based on biological variation for imprecision and showed good agreement with central laboratory. The two assays were unaffected by hematocrit variation between 20 and 70%, hemolysis and icterus interferences. It should be noted that the relationship between lab methods and ABL90 was conserved even for high pre-dialysis values allowing easy access to dialysis adequacy parameters ( Kt / V ) and muscle mass evaluation (creatinine index). Rapid measurement of creatinine and urea using whole blood specimens on ABL90 appears as a fast and convenient method. Analytical performances were in accordance with our expectations without any significant interferences by hemolysis or icterus.

Background: Adverse childhood events may have differential effects on the brain that persist into adulthood. Findings on structural brain alterations in older adults exposed to early-life adversity are inconsistent notably due to heterogeneity in imaging studies, population, psychiatric comorbidities, nature of adverse events, and genetic vulnerability. This study examines whether exposure related to physical or sexual maltreatment, emotional maltreatment, and global adverse environment during childhood are associated with specific alterations in grey matter volumes and if this varies according to sex and serotonin transporter-linked promoter region (5-HTTLPR) genotype., Method: Structural MRI was used to acquire anatomical scans from 398 community-dwelling older adults. Quantitative regional estimates of 23 subregional volumes were derived using FreeSurfer software. Retrospective reporting of childhood adversity was collected using structured self-reported questionnaire. Analyses adjusted for age, sex, brain volume, head injury, lifetime depression and anxiety disorder, psychiatric medication, and cardiovascular ischemic pathologies., Results: Exposure to adverse family environment was associated with smaller volumes of several frontal, cingulate, and parietal subregions and larger amygdala in the 5-HTTLPR SS genotype participants specifically but larger volumes of caudate, putamen, pallidum, and nucleus accumbens in the SL genotype participants. Highly significant differences were found with excessive sharing of parent problems with children, associated with larger grey-matter volumes in the thalamus and several frontal and parietal regions in 5-HTTLPR SL male participants specifically., Conclusions: Early-life adversity is associated with grey-matter volume alterations in older adults and this varies according to the type of adversity experienced, sex, and serotonergic genetic vulnerability; 5-HTTLPR SS participants appearing most vulnerable and SL individuals most resilient., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

We tested the hypothesis that a particular immune activation profile might be correlated with insulin resistance in a general population. By measuring 43 markers of immune, endothelial, and coagulation activation, we have previously shown that five different immune activation profiles may be distinguished in 150 volunteers. One of these profiles, Profile 2, characterized by CD4+ T cell senescence, inflammation, monocyte, B cell, and endothelial activation, presented elevated insulinemia, glycemia, triglyceridemia, and γ-glutamyl transferase, a marker of liver injury, in comparison with other profiles. Our data are compatible with a model in which a particular immune activation profile might favor the development of insulin resistance and metabolic syndrome. In this hypothesis, identification of this profile, that is feasible with only 3 markers with an error rate of 5%, might allow to personalize the screening and prevention of metabolic syndrome-driven morbidities as liver steatosis.

Objectives: A newly developed fully automated Lumipulse G AMH method (Fujirebio Diagnostics) was recently introduced in clinical laboratories for quantitative determination of anti-Müllerian hormone (AMH) level in human serum or plasma. AMH has emerged as value-added biomarker in the assessment of ovarian reserve, in diagnosis of granulosa cells cancer and in the investigation of gonadal disorders. We compared Lumipulse G AMH assay performances with other methods largely applied for AMH measurements., Design and Methods: The Lumipulse G AMH method based on two-step sandwich chemiluminescence enzyme immunoassay was assessed on Lumipulse G600II analyzer. The evaluation study included imprecisions, sensitivity and linearity whereas a comparison study was performed on a heterogeneous population of 114 patients by using the Elecsys AMH Plus assay on COBAS 8000 e602 module (Roche Diagnostics)., Results: Lumipulse G AMH system showed good repeatability (within-run imprecision) with CV values below 1% (0.5% and 0.9% for high and low serum pools). Similarly within-laboratory imprecision was assessed with CV values of 2.5% and 1.6% for high and low level controls respectively. A linearity regression formula of 1.0119x-0.067 with a coefficient of determination (r 2 ) equal to 0.999 was obtained in a range from 0.044 to 22.42 ​ng/ml. Passing-Bablok regression analysis was performed for assay comparability of AMH measurements. Results were closely correlated (correlation coefficient ​= ​0.997) with a regression equation (y ​= ​1.230x-0.025) showing a positive slope. Also, Bland-Altman analysis confirmed a good agreement between Lumipulse G AMH and Roche Elecsys AMH Plus assays with a bias of 17.76% in a large measurement range., Conclusions: The performance of Lumipulse G AMH system was highly comparable with that of Roche Elecsys AMH Plus assay although approximately 10% higher values of AMH levels were observed for Lumipulse AMH system at all range of concentrations. Nevertheless the Lumipulse G system seems to be largely suitable for quantitative determination of AMH level in small-scale laboratory because of the reduced size and the use of single cartridge per test assuring flexibility and easy handling., Competing Interests: None., (© 2021 The Authors.)

Background: In coronavirus disease 2019 (COVID-19) patients, increases in high-sensitive cardiac troponin T (hs-cTnT) have been reported to be associated with worse outcomes. In the critically ill, the prognostic value of hs-cTnT, however, remains to be assessed given that most previous studies have involved a case mix of non- and severely ill COVID-19 patients., Methods: We conducted, from March to May 2020, in three French intensive care units (ICUs), a multicenter retrospective cohort study to assess in-hospital mortality predictability of hs-cTnT levels in COVID-19 patients., Results: 111 laboratory-confirmed COVID-19 patients (68% of male, median age 67 (58-75) years old) were included. At ICU admission, the median Charlson Index, Simplified Acute Physiology Score II, and PaO 2 /FiO 2 were at 3 (2-5), 37 (27-48), and 140 (98-154), respectively, and the median hs-cTnT serum levels were at 16.0 (10.1-31.9) ng/L. Seventy-five patients (68%) were mechanically ventilated, 41 (37%) were treated with norepinephrine, and 17 (15%) underwent renal replacement therapy. In-hospital mortality was 29% (32/111) and was independently associated with lower PaO 2 /FiO 2 and higher hs-cTnT serum levels., Conclusions: At ICU admission, besides PaO 2 /FiO 2 , hs-cTnT levels may allow early risk stratification and triage in critically ill COVID-19 patients.

Background: Whether soluble urokinase-type plasminogen activator receptor (suPAR) could be a valuable prognostic indicator remains uncertain., Materials & Methods: Patients from STADE-HF (Soluble Suppression of Tumorigenesis-2 as a Help for Management of Diagnosis, Evaluation and Management of Heart Failure) were included for analysis., Results: 95 patients were included. The suPAR level of expression was significantly higher in the group of patients who died at one month (7.90 ± 4.35 ng/ml vs 11.94 ± 6.86 ng/ml; p < 0.05) or 1 year (7.28 ± 4.27 ng/ml vs 11.81 ± 4.88 ng/ml; p < 0.01), but there was no significant difference according to the readmission., Conclusion: High suPAR levels during hospitalization for acute heart failure were highly predictive for the risk of mortality, but not the risk of readmission., Competing Interests: Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript., (© 2021 Fabien Huet.)

Objectives: Inflammation is a hallmark of heart failure (HF) and among inflammatory biomarkers, the most studied remains the C-reactive protein (CRP). In recent years several biomarkers have emerged, such as sST2 and soluble urokinase-type plasminogen activator receptor (suPAR). This study set out to examine the relative importance of long-time prognostic strength of suPAR and the potential additive information on patient risk with chronic HF in comparison with pronostic value of CRP and sST2., Methods: Demographics, clinical and biological variables were assessed in a total of 182 patients with chronic HF over median follow-up period of 80 months. Inflammatory biomarkers (i.e., CRP, sST2, and suPAR) were performed., Results: In univariate Cox regression analysis age, NYHA class, MAGGIC score and the five biomarkers (N-terminal pro brain natriuretic peptide [NT-proBNP], high-sensitive cardiac troponin T [hs-cTnT], CRP, sST2, and suPAR) were associated with both all-cause and cardiovascular mortality. In the multivariate model, only NT-proBNP, suPAR, and MAGGIC score remained independent predictors of all-cause mortality as well as of cardiovascular mortality. Risk classification analysis was significantly improved with the addition of suPAR particularly for all-cause short- and long-term mortality. Using a classification tree approach, the same three variables could be considered as significant classifier variables to predict all-cause or cardiovascular mortality and an algorithm were reported. We demonstrated the favorable outcome associated with patients with a low MAGGIC score and a low suPAR level by comparison to patients with low MAGGIC score but high suPAR values., Conclusions: The main findings of our study are (1) that among the three inflammatory biomarkers, only suPAR levels were independently associated with 96-month mortality for patients with chronic HF and (2) that an algorithm based on clinical score, a cardiomyocyte stress biomarker and an inflammatory biomarker could help to a more reliable long term risk stratification in heart failure., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Latent infectious agents, microbial translocation, some metabolites and immune cell subpopulations, as well as senescence modulate the level and quality of activation of our immune system. Here, we tested whether various in vivo immune activation profiles may be distinguished in a general population. We measured 43 markers of immune activation by 8-color flow cytometry and ELISA in 150 adults, and performed a double hierarchical clustering of biomarkers and volunteers. We identified five different immune activation profiles. Profile 1 had a high proportion of naïve T cells. By contrast, Profiles 2 and 3 had an elevated percentage of terminally differentiated and of senescent CD4+ T cells and CD8+ T cells, respectively. The fourth profile was characterized by NK cell activation, and the last profile, Profile 5, by a high proportion of monocytes. In search for etiologic factors that could determine these profiles, we observed a high frequency of naïve Treg cells in Profile 1, contrasting with a tendency to a low percentage of Treg cells in Profiles 2 and 3. Moreover, Profile 5 tended to have a high level of 16s ribosomal DNA, a direct marker of microbial translocation. These data are compatible with a model in which specific causes, as the frequency of Treg or the level of microbial translocation, shape specific profiles of immune activation. It will be of interest to analyze whether some of these profiles drive preferentially some morbidities known to be fueled by immune activation, as insulin resistance, atherothrombosis or liver steatosis.

Objective: To evaluate the association of baseline serum level of vitamin D 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. Levels of 25-hydroxy vitamin D2 and D3 were measured at baseline. Baseline associations between vitamin D level and 28-joint count Disease Activity Score based on erythrocyte sedimentation rate (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 vitamin D 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 patients with RA were analyzed. Vitamin D level was < 10 ng/mL (deficiency, group 1), 10-29.9 ng/mL (low level, group 2), and ≥ 30 ng/mL (normal, group 3) for 114 (17.7%), 415 (64.54%), and 114 (17.7%) patients, respectively. At baseline, DAS28-ESR and HAQ-DI were higher with vitamin D deficiency 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 vitamin D deficiency was associated with HAQ-DI at 6 months (OR 1.70) and mTSS at 12 months (OR 1.76)., Conclusion: Vitamin D 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. [ClinicalTrials.gov: NCT03666091].