Biological variation of inflammatory and iron metabolism markers in high-endurance recreational athletes; are these markers useful for athlete monitoring?

OBJECTIVES: To deliver biological variation (BV) data for serum hepcidin, soluble transferrin receptor (sTfR), erythropoietin (EPO) and interleukin 6 (IL-6) in a population of well-characterized high-endurance athletes, and to evaluate the potential influence of exercise and health-related factors on the BV. METHODS: Thirty triathletes (15 females) were sampled monthly (11 months). All samples were analyzed in duplicate and BV estimates were delivered by Bayesian and ANOVA methods. A linear mixed model was applied to study the effect of factors related to exercise, health, and sampling intervals on the BV estimates. RESULTS: Within-subject BV estimates (CVI) were for hepcidin 51.9 % (95 % credibility interval 46.9-58.1), sTfR 10.3 % (8.8-12) and EPO 27.3 % (24.8-30.3). The mean concentrations were significantly different between sex, but CVI estimates were similar and not influenced by exercise, health-related factors, or sampling intervals. The data were homogeneously distributed for EPO but not for hepcidin or sTfR. IL-6 results were mostly below the limit of detection. Factors related to exercise, health, and sampling intervals did not influence the BV estimates. CONCLUSIONS: This study provides, for the first time, BV data for EPO, derived from a cohort of well-characterized endurance athletes and indicates that EPO is a good candidate for athlete follow-up. The application of the Bayesian method to deliver BV data illustrates that for hepcidin and sTfR, BV data are heterogeneously distributed and using a mean BV estimate may not be appropriate when using BV data for laboratory and clinical applications.

Cadmium exposure and growth differentiation factor-15 (GDF-15) levels in non-smoking older adults.

BACKGROUND: Cadmium (Cd) exposure is a risk factor for cardiovascular disease (CVD); however, understanding the effects of Cd at the cellular level remains incomplete. Since growth differentiation factor-15 (GDF-15) is a cytokine produced in many cell types in response to tissue injury and inflammation that may capture several pathways between Cd and CVD, this study examined the relationship between blood Cd levels and serum GDF-15 concentrations in community-dwelling older adults. METHODS: Cd and GDF-15 were measured in 1942 non-smoking individuals aged 65+ with no previous history of CVD. The association of Cd with GDF-15 was evaluated in linear regression models that adjusted for sociodemographic, lifestyle and biological risk factors, inflammatory biomarkers (IL-6, C-reactive protein and neutrophil to lymphocyte ratio), and markers of vascular damage (NTproBNP and cTnT-hs). RESULTS: Geometric mean Cd exposure was 0.11 µg/L (0.09 in never- and 0.15 in former-smokers) and geometric mean GDF-15 was 1186.21 pg/mL (1182.67 in never- and 1191.66 in former-smokers). In multivariable analyses, we found a dose-response association between Cd levels and GDF-15: adjusted mean percentage differences in GDF-15 (95% confidence interval) per 2-fold increase in Cd concentrations in the overall non-smoking population and in never smokers were, respectively, 2.54% (1.01, 4.06) and 2.50% (0.47, 4.54). In spline regression, the dose-response relationship was progressive over the range of Cd concentrations with no significant departures from linearity. CONCLUSIONS: Cd exposure may be related to enhanced GDF-15 expression. Future studies with repeated GDF-15 measurements should confirm the present findings to better understand the biological mechanisms underlying this association.

Bone mineral density and inflammatory and bone biomarkers after darunavir-ritonavir combined with either raltegravir or tenofovir-emtricitabine in antiretroviral-naive adults with HIV-1: a substudy of the NEAT001/ANRS143 randomised trial.

BACKGROUND: Osteopenia, osteoporosis, and low bone mineral density are frequent in patients with HIV. We assessed the 96 week loss of bone mineral density associated with a nucleoside or nucleotide reverse transcriptase inhibitor (NtRTI)-sparing regimen. METHODS: Antiretroviral-naive adults with HIV were enrolled in 78 clinical sites in 15 European countries into a randomised (1:1), open-label, non-inferiority trial (NEAT001/ANRS143) assessing the efficacy and safety of darunavir (800 mg once per day) and ritonavir (100 mg once per day) plus either raltegravir (400 mg twice per day; NtRTI-sparing regimen) or tenofovir (245 mg once per day) and emtricitabine (200 mg once per day; standard regimen). For this bone-health substudy, 20 of the original sites in six countries participated, and any patient enrolled at one of these sites who met the following criteria was eligible: plasma viral loads greater than 1000 HIV RNA copies per mL and CD4 cell counts of fewer than 500 cells per µL, except in those with symptomatic HIV infection. Exclusion criteria included treatment for malignant disease, testing positive for hepatitis B virus surface antigen, pregnancy, creatinine clearance less than 60 mL per min, treatment for osteoporosis, systemic steroids, or oestrogen-replacement therapy. The two primary endpoints were the mean percentage changes in lumbar spine and total hip bone mineral density at week 48, assessed by dual energy x-ray absorptiometry (DXA) scans. We did the analysis with an intention-to-treat-exposed approach with antiretroviral modifications ignored. The parent trial is registered with ClinicalTrials.gov, number NCT01066962, and is closed to new participants. FINDINGS: Between Aug 2, 2010, and April 18, 2011, we recruited 146 patients to the substudy, 70 assigned to the NtRTI-sparing regimen and 76 to the standard regimen. DXA data were available for 129, 121 and 107 patients at baseline, 48 and 96 weeks respectively. At week 48, the mean percentage loss in bone mineral density in the lumbar spine was greater in the standard group than in the NtRTI-sparing group (mean percentage change -2.49% vs -1.00%, mean percentage difference -1.49, 95% CI -2.94 to -0.04; p=0.046). Total hip bone mineral density loss was similarly greater at week 48 in the standard group than in the NtRTI-sparing group (mean percentage change -3.30% vs -0.73%; mean percentage difference -2.57, 95% CI -3.75 to -1.35; p<0.0001). Seven new fractures occurred during the trial (two in the NtRTI-sparing group and five in the standard group). INTERPRETATION: A raltegravir-based regimen was associated with significantly less loss of bone mineral density than a standard regimen containing tenofovir disoproxil fumarate, and might be a treatment option for patients at high risk of osteopenia or osteoporosis who are not suitable for NtRTIs such as abacavir or tenofovir alafenamide. FUNDING: The European Union Sixth Framework Programme, Inserm-ANRS, Ministerio de Sanidad y Asuntos Sociales de España, Gilead Sciences, Janssen Pharmaceuticals, and Merck Laboratories.

Clinical, operational and economic outcomes of point-of-care blood gas analysis in COPD patients.

INTRODUCTION: Arterial blood gas analysis is relevant in chronic obstructive pulmonary disease (COPD) management. The aim of this study was to evaluate whether the use of a blood gas analyzer in pulmonology departments improves the clinical, operational and economic outcomes when compared with clinical laboratory measurements. PATIENTS AND METHODS: It is an observational prospective study. 112 patients were selected. After specimen collection, the measurement was performed both in pulmonology office as point-of-care and in laboratory. We evaluated clinical outcomes (modification of the indication of long-term oxygen therapy (LTOT) according to results, changes in blood gas analysis results, relationship of the partial pressure of oxygen (PaO2) obtained in the medical visit and velocity of change of the PaO2, influence of total haemoglobin concentration and the change in PaO2), operational outcomes (turnaround time (TAT) from specimen collection to receiving the blood gas analysis report) and economic outcomes (overall cost per process of patient care). RESULTS: There were discrepancies in the indication of LTOT in 13.4% of patients. All parameters showed changes. PaO2 levels showed changes in 2 ways, though they frequently increase over time. The correlation was not good in the other two clinical outcomes. The median TATs in pulmonology office were 1 min versus 79 in laboratory, with 52 min for specimen preparation and transport and 17 min for TAT intralaboratory. The overall cost for the 112 patients in pulmonology office and laboratory was 16,769.89€ and 22,260.97€ respectively. CONCLUSIONS: The use of a blood gas analyzer in a pulmonology office improves clinical, operational and economic outcomes when compared with clinical laboratory.

Procalcitonin-guided therapy may reduce length of antibiotic treatment in intensive care unit patients with secondary peritonitis: A multicenter retrospective study.

PURPOSE: Because procalcitonin (PCT) might be surrogate for antimicrobial discontinuation in general intensive care units (ICUs), this study explored its use for secondary peritonitis in 4 surgical ICUs (SICUs). METHODS: A retrospective study including all consecutive patients with secondary peritonitis, controlled infection source, requiring surgery, and at least 48-hour SICU admission was performed (June 2012-June 2013). Patients were divided following notations in medical records into PCT-guided (notation of PCT-based antibiotic discontinuation) and non-PCT-guided (no notation) groups. RESULTS: A total of 121 patients (52 PCT-guided, 69 non-PCT-guided) were included. No differences in clinical scores, biomarkers, or septic shock (30 [57.7%] PCT-guided vs 40 [58.0%] non-PCT-guided) were found. Length of intra-SICU (median, 5.0 days; both groups) or in-hospital (median, 20.0 vs 17.5 days) stay, and mortality intra-SICU (9.6% vs 13.0%), 28-day (15.4% vs 20.3%), or in-hospital (19.2% vs 29.0%) were not significantly different (PCT-guided vs non-PCT-guided). In septic shock patients, no mortality differences were found (PCT-guided vs non-PCT-guided): 16.7% vs 22.5% (intra-SICU), 26.7% vs 32.5% (28-day), and 33.3% vs 42.5% (in-hospital). Treatment was shorter in the PCT-guided group (5.1 ±2.1 vs 10.2 ± 3.7 days, P < .001), without differences between patients with and without septic shock. CONCLUSION: Procalcitonin guidance produced 50% reduction in antibiotic duration (P < .001, log-rank test).

Phase 1 study of two inodilators in neonates undergoing cardiovascular surgery.

BACKGROUND: Inodilators are routinely used in cardiovascular surgery with cardiopulmonary bypass (CPB). Information regarding safety and tolerability of the novel molecule, levosimendan (LEVO), in newborns is anecdotal; no pharmacokinetic data in this population are available. METHODS: This was a phase I, randomized, and blinded study. Neonates undergoing surgical repair for congenital heart defects received stepwise dose increases of milrinone (MR; 0.5-1 µg/kg/min, n = 9) or LEVO (0.1-0.2 µg/kg/min, n = 11) as an i.v. continuous infusion, starting before CPB. Infants had continuous, time-locked, physiological, and near-infrared spectroscopy (NIRS) (cerebral and peripheral) recordings during the first 24 h, and at 48 and 96 h postsurgery. Serial biochemistry and pharmacokinetic studies were performed. RESULTS: During the first 24 h postsurgery, patients showed time-related, group-independent increased cerebral tissue oxygenation and decreased diastolic blood pressure; in addition, group-dependent differences in heart rate and peripheral perfusion were found. Early postsurgery, MR-treated infants showed lower pH, higher glycemia, and higher inotrope score. The groups differed in cerebral NIRS-derived variables from 24 to 96 h. Study drug withdrawal at 96 h was more frequent with LEVO. LEVO intermediate metabolites were detected in plasma at day 14 after surgery. CONCLUSION: LEVO is well tolerated in critically ill neonates. LEVO may have advantages over MR in terms of the dosing regimen.

Minimum analytical quality specifications of inter-laboratory comparisons: agreement among Spanish EQAP organizers.

BACKGROUND: Four Spanish scientific societies organizing external quality assessment programs (EQAP) formed a working group to promote the use of common minimum quality specifications for clinical tests. Laboratories that do not meet the minimum specifications are encouraged to make immediate review of the analytical procedure affected and to implement corrective actions if necessary. METHODS: The philosophy was to use the 95th percentile of results sent to EQAP (expressed in terms of percentage deviation from the target value) obtained for all results (except the outliers) during a cycle of 1 year. The target value for a number of analytes of the basic biochemistry program was established as the overall mean. However, because of the substantial discrepancies between routine methods for basic hematology, hormones, proteins, therapeutic drugs and tumor markers, the target in these cases was the peer group mean. RESULTS: The resulting specifications were quite similar to those established in the US (CLIA), and Germany (Richtlinie). CONCLUSIONS: The proposed specifications stand for the minimum level of quality to be attained for laboratories, to assure harmonized service performance. They have nothing to do with satisfying clinical requirements, which are the final level of quality to be reached, and that is strongly recommended in our organizations by means of documents, courses, symposiums and all types of educational activities.