Sample management for clinical biochemistry assays: Are serum and plasma interchangeable specimens?

The constrained economic context leads laboratories to centralize their routine analyses on high-throughput platforms, to which blood collection tubes are sent from peripheral sampling sites that are sometimes distantly located. Providing biochemistry results as quickly as possible implies to consolidate the maximum number of tests on a minimum number of blood collection tubes, mainly serum tubes and/or tubes with anticoagulants. However, depending on the parameters and their pre-analytical conditions, the type of matrix - serum or plasma - may have a significant impact on results, which is often unknown or underestimated in clinical practice. Importantly, the matrix-related effects may be a limit to the consolidation of analyses on a single tube, and thus must be known by laboratory professionals. The purpose of the present critical review is to put forward the main differences between using serum and plasma samples on clinical biochemistry analyses, in order to sensitize laboratory managers to the need for standardization. To enrich the debate, we also provide an additional comparison of serum and plasma concentrations for approximately 30 biochemistry parameters. Properties, advantages, and disadvantages of serum and plasma are discussed from a pre-analytical standpoint - before, during, and after centrifugation - with an emphasis on the importance of temperature, delay, and transport conditions. Then, differences in results between these matrices are addressed for many classes of biochemistry markers, particularly proteins, enzymes, electrolytes, lipids, circulating nucleic acids, metabolomics markers, and therapeutic drugs. Finally, important key-points are proposed to help others choose the best sample matrix and guarantee quality of clinical biochemistry assays. Moreover, awareness of the implications of using serum and plasma samples on various parameters assayed in the laboratory is an important requirement to ensure reliable results and improve patient care.

Prevalence of obesity hypoventilation syndrome in ambulatory obese patients attending pathology laboratories.

BACKGROUND AND OBJECTIVE: The prevalence of obesity hypoventilation syndrome (OHS) in the unselected obese is unknown. Our objectives were: (i) to determine the prevalence of OHS in ambulatory obese patients not previously referred to a pulmonologist for suspicion of sleep breathing disorders and (ii) to assess whether venous bicarbonate concentration [HCO3-v ] can be used to detect OHS. METHODS: In this prospective multicentric study, we measured [HCO3-v ] in consenting obese patients attending pathology analysis laboratories. Patients with [HCO3-v ] ≥ 27 mmol/L were referred to a pulmonologist for comprehensive sleep and respiratory evaluations. Those with [HCO3-v ] < 27 mmol/L were randomized to either referral to a pulmonologist or ended the study. RESULTS: For the 1004 screened patients, the [HCO3-v ] was ≥27 mmol/L in 24.6% and <27 mmol/L in 45.9%. A total of 29.5% who had previously consulted a pulmonologist were excluded. A population of 241 obese patients underwent sleep and respiratory assessments. The prevalence of OHS in this population was 1.10 (95% CI = 0.51; 2.27). In multivariate analysis, PaCO2 , forced expiratory volume in 1 s (FEV1 ), apnoea-hypopnoea index (AHI), BMI, use of ≥3 anti-hypertensive drugs, anti-diabetics, proton pump inhibitors and/or paracetamol were related to raised [HCO3-v ]. CONCLUSION: The prevalence of OHS in our obese population was lower than previous estimations based on hospitalized patients or clinical cohorts with sleep breathing disorders. Apart from hypercapnia, increased [HCO3-v ] may also reflect multimorbidity and polypharmacy, which should be taken into account when using [HCO3-v ] to screen for OHS.

[Moving towards a personalized oncology: The contribution of genomic techniques and artificial intelligence in the use of circulating tumor biomarkers]. / En marche vers une oncologie personnalisée : l'apport des techniques génomiques et de l'intelligence artificielle dans l'usage des biomarqueurs tumoraux circulants.

Technological advances, in particular the development of high-throughput sequencing, have led to the emergence of a new generation of molecular biomarkers for tumors. These new tools have profoundly changed therapeutic management in oncology, with increasingly precise molecular characterization of tumors leading to increasingly personalized therapeutic targeting. Detection of circulating tumor cells and/or circulating tumor DNA in blood samples -so-called 'liquid biopsies'- can now provide a genetic snapshot of the patient's tumor through an alternative and less invasive procedure than biopsy of the tumor tissue itself. This procedure for characterizing and monitoring the disease in real time facilitates the search for possible relapses, the emergence of resistance, or emergence of a new therapeutic target. In the long term, it might also provide a means of early detection of cancer. These new approaches require the treatment of ever-increasing amounts of clinical data, notably, with the goal of calculating composite clinical-biological predictive scores. The use of artificial intelligence will be unavoidable in this domain, but it raises ethical questions and implications for the health-care system that will have to be addressed.

[Clinical use and evolution of circulating biomarkers in the era of personalized oncology: From protein markers to bioclinical scores]. / Utilisation clinique et évolution des biomarqueurs circulants à l'ère de l'oncologie personnalisée : des marqueurs protéiques aux scores clinicobiologiques.

In oncology, the identification of targets that correlate with a type of cancer has led to a profound change in the notion of "tumor markers". Technological advances, in particular the development of high-throughput sequencing, have led to the emergence of a new generation of molecular biomarkers for tumors. Despite their limited utility for screening and diagnosis, conventional tumor markers remain interesting for evaluation of prognoses, the choice and optimization of treatments, as well as for monitoring the effectiveness of those treatments. In this article, we revisit the conventional serum markers that are enjoying a 'come back' thanks to the development of high-performance scores based on biological, cytological, clinical, or radiological criteria.

[Use of « Reference change value ¼ in medical biology: about two examples: total PSA and hemoglobin]. / Utilisation de la « Reference change value ¼ en biologie médicale : à propos de deux exemples : PSA total et hémoglobine.

The interpretation of the variation between the results of two dosages performed on the same patient is generally quite empirical. It is usually based on the experience of the biologist or physician. Through two examples, total PSA and hemoglobin, we hoped to set up an indicator of the significance variation between results: The Reference change value or RCV to provide assistance to the validator biologist and prescriber based on measured statistical arguments. This article describes the methodology used for the RCV calculation, the formatting on analysis reports and the limitations of the system.

Discrepancies between the Cockcroft-Gault and Chronic Kidney Disease Epidemiology (CKD-EPI) Equations: Implications for Refining Drug Dosage Adjustment Strategies.

INTRODUCTION: The dosages of many medications require adjustment for renal function. There is debate regarding which equation, the Chronic Kidney Disease Epidemiology (CKD-EPI) equation vs. the Cockcroft-Gault (CG) equation, should be recommended to estimate glomerular filtration rate. METHODS: We used a mathematical simulation to determine how patient characteristics influence discrepancies between equations and analyzed clinical data to demonstrate the frequency of such discrepancies in clinical practice. In the simulation, the modifiable variables were sex, age, serum creatinine, and weight. We considered estimated glomerular filtration rate results in mL/min, deindexed for body surface area, because absolute excretory function (rather than per 1.73 m2 body surface area) determines the rate of filtration of a drug at a given plasma concentration. An absolute and relative difference of maximum (±) 10 mL/min and 10 %, respectively, were considered concordant. Clinical data for patients aged over 60 years (n = 9091) were available from one hospital and 25 private laboratories. RESULTS: In the simulation, differences between the two equations were found to be influenced by each variable but age and weight had the biggest effect. Clinical sample data demonstrated concordance between CKD-EPI and CG results in 4080 patients (45 %). The majority of discordant results reflected a CG result lower than the CKD-EPI equation. With aging, the CG result became progressively lower than the CKD-EPI result. When weight increased, the opposite occurred. DISCUSSION: The choice of equation for excretory function adjustment of drug dosage will have different implications for patients of different ages and body habitus. CONCLUSIONS: The optimum equation for drug dosage adjustment should be defined with consideration of individual patient characteristics.

Evolution of EBV seroprevalence and primary infection age in a French hospital and a city laboratory network, 2000-2016.

BACKGROUND: According to rare studies, the age at EBV primary infection (PI) has recently risen in some developed countries. A later age at infection is generally considered a risk factor for severe EBV PI, although few studies exist on this subject. Our investigation aimed to determine whether EBV seroprevalence and EBV PI epidemiology have evolved in France, and to what extent age and infection intensity (regarding biological parameters) are correlated. METHODS AND FINDINGS: We conducted a retrospective study of the following EBV serological tests databases: tests carried out at Grenoble University Hospital (2000-2016) (n = 53,553); and tests carried out by a network of city laboratories in Grenoble area (2008-2015) (n = 27,485). The hospital population showed a continuous, significant decrease in EBV seroprevalence over the studied period for patients aged 20 and over (p<0.01). The seroprevalence also decreased for different age classes (<10, 15-19, 20-30, and 30-40 years old) over the periods 2001-2005, 2006-2010, and 2011-2015. Consistently, the age at PI was significantly higher in the years 2008-2015 than in the years 2001-2007 (15.6±12.0 vs. 13.7±11.0; p = 0.03). The city laboratory population showed the same trend of decreasing seroprevalence (p = 0.06); no significant variations in age at PI were observed. The age at PI was positively correlated with ASAT, ALAT, γGT, and bilirubin blood levels (p<0.01) and negatively correlated with platelet counts (p<0.05). CONCLUSION: In the last 15 years, the age at EBV PI has increased, whereas seroprevalence has decreased. Moreover, our findings confirm the positive correlation between age and biological abnormalities. Taken together, these results suggest that the incidence of severe EBV PI will increase in the future.

[Dosing adjustment and renal function: Which equation(s)?]. / Adaptation posologique des médicaments et fonction rénale : quel(s) estimateur(s) faut-il choisir ?

While the CKD-EPI (for Chronic Kidney Disease Epidemiology) equation is now implemented worldwide, utilization of the Cockcroft formula is still advocated by some physicians for drug dosage adjustment. Justifications for this recommendation are that the Cockcroft formula was preferentially used to determine dose adjustments according to renal function during the development of many drugs, better predicts drugs-related adverse events and decreases the risk of drug overexposure in the elderly. In this opinion paper, we discuss the weaknesses of the rationale supporting the Cockcroft formula and endorse the French HAS (Haute Autorité de santé) recommendation regarding the preferential use of the CKD-EPI equation. When glomerular filtration rate (GFR) is estimated in order to adjust drug dosage, the CKD-EPI value should be re-expressed for the individual body surface area (BSA). Given the difficulty to accurately estimate GFR in the elderly and in individuals with extra-normal BSA, we recommend to prescribe in priority monitorable drugs in those populations or to determine their "true" GFR using a direct measurement method.

Drugs influencing acid base balance and bicarbonate concentration readings.

Serum bicarbonate dosage is sensitive to pharmacological interferences. However, elevated bicarbonate concentration reflects chronic hypoventilation and has been proposed as a simple marker for screening patients with Obesity Hypoventilation Syndrome (OHS), a currently underdiagnosed multimorbid and high mortality disease. We provide a practical overview of the different drugs acting on the acid-base equilibrium to aid clinicians to interpret bicarbonate concentration readings. Little is known about the chronic impact of the usual doses of these drugs on serum bicarbonate concentration and further studies are needed. It is essential to take into account drugs that could interfere with this parameter to avoid misinterpretation of serum bicarbonate levels.