Predicting One-Year Mortality after Discharge Using Acute Heart Failure Score (AHFS).

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.

Free hemoglobin determination at patients' bedside to evaluate hemolysis.

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.

Monitoring of ionized magnesium in hemodialysis patients: A useful tool to allow a personalized prescription of dialysate composition.

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.

Use of dried blood spots for monitoring inflammatory and nutritional biomarkers in the elderly.

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.

Acute kidney injury in critical COVID-19 patients: usefulness of urinary biomarkers and kidney proximal tubulopathy.

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/m2 (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.

Feedback on the Implementation of a Rapid and Connectable Point-of-Care COVID-19 Antigen Test in an Emergency Department.

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.

The pivotal role of HbA1c assay to detect hemoglobinopathies: A 5-year observational retrospective study in the population of Southern France.

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.

New Perspectives of Multiplex Mass Spectrometry Blood Protein Quantification on Microsamples in Biological Monitoring of Elderly Patients.

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.

Eater-oriented knowledge framework for reducing salt and dietary sodium intake (scoping review).

Salt and dietary sodium are ubiquitously present in daily food practices and, at the same time, reducing salt intake presents an important public health issue. Given such an ambivalent position of salt in human diet, we argue that public health guidelines toward dietary sodium reduction require an eater-oriented knowledge framework. In this article we are making the first steps toward a flexible interdisciplinary database which would include nutritional, socio-economic, cultural, material, and socio-psychological determinants of salt consumption for comprehensive public health campaigns. We employ an explorative scoping review of academic articles and reports, limiting our review to the original data on salt or sodium consumption published in English or French between 2000 and 2022. We describe salt consumption as research object, identifying its representation in different research fields, data sources, methodologies, samples, and links with nutritional recommendations. We synthesize existing approaches via four eater-oriented categories: Socio-demographic and cultural descriptors of salt consumers; Knowledge, attitudes, and beliefs on nutritional norms; Salt practices associated with dietary or medical regimes; Salt materialities: interactions and contexts. In each category, we identify the dominant relational features, i.e., what kind of 'eater-salt' relation is being put forward. We thus build an interdisciplinary documentary base of dietary sodium consumption factors. We discuss the results, suggesting that comprehensive nutritional policies for global salt reduction require interdisciplinary eater-oriented data frameworks.

Analytical Performances of the Novel i-STAT Alinity Point-of-Care Analyzer.

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.

Analytical evaluation and bioclinical validation of new aldosterone and renin immunoassays.

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 (R2=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.

A case of inter-assay HbA1c discrepancy due to Hemoglobin G-Copenhagen.

BACKGROUND AND OBJECTIVE: A clinician was intrigued about HbA1c upper 9% (75 mmol/mol) in a 76 year-old women with normal glycemia. Further explorations were performed in order to understand this discordance. METHODS: First HbA1c test was performed on a HLC -723 G11 apparatus (Tosoh Bioscience) and thereafter compared to the HLC-723-G8 (Tosoh Bioscience), the Capillaris 3 Tera (Sebia) and the DCA Vantage point of care testing (POCT) (Siemens) apparatus. In addition, study of Hemoglobin (Hb) fraction and mutation analysis of HBB gene was realized due to the suspicion of an Hb variant. RESULTS: Twice high results of HbA1c (9.3%, 78 mmol/mol and 10%, 86 mmol/mol) on the HLC-723 G11 was not confirmed with other instruments. HbA1c result for the same sample was 5.2% (33 mmol/mol) for the HLC-723 G8, 5.3% (34 mmol/mol) for the Capillaris and 6.2% (44 mmol/mol) for the DCA Vantage POCT. The subject had normal glycemia and none signs of diabetes mellitus. An abnormal Hb fraction was visualized on the graphs for the HLC-723 G11 and Capillaris but not for the HLC-723 G8 analyzer. Study of Hb fraction confirmed the presence of an abnormal Hb fraction that was identifed as an Hb G-Copenhagen through mutation analysis of HBB gene. CONCLUSION: This case evidenced an interference on HbA1c test in presence of Hb G-Copenhagen depending to the analyzer used. This report help to alert of such possibility and to remain that a discordance between HbA1c and glycemia can be due to an Hb variant.

In patients with anorexia nervosa, myokine levels are altered but are not associated with bone mineral density loss and bone turnover alteration.

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.

Fibroblast growth factor 19 stimulates water intake.

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.

Comparative study of human growth hormone measurements: impact on clinical interpretation.

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 (r2>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.