Translating the power of high-throughput sequencing technologies from research area into clinical medicine is one of the major goal for several researchers and health-care providers. One of the important advantages of these technologies is that they can be successfully used in a numerous range of clinical applications. The efficiency of sequencing, that can now be achieved, is leading impressive progress in the diagnostics of common and rare genetic disorders, inherited forms of cancer, prenatal testing or infectious diseases, to cite some examples. Despite several challenges and limitations still remain to overcome, the high-throughput sequencing technologies are leading to real and unprecedented benefits for the medical care of patients.

With an aging population, there is a marked increase in prevalence of metabolic bone diseases, especially osteoporosis. Perhaps the most dreaded complication of metabolic bone disease, fractures typically impose a huge burden on the ailing body and are associated with high co-morbidity and mortality. The consequent public health and socioeconomic burden warrant timely diagnosis, treatment and follow-up of these disorders. Knowing the limitations of radiological techniques, biochemical markers of bone turnover measurements come handy since the changes in their levels readily reflect bone physiology. Bone biomarkers typically analyzed in high throughput automated routine laboratories are collagen degradation products, reflecting osteoclast activity, and the collagenous or non-collagenous proteins produced by the osteoblasts. Since bone biomarker levels vary considerably due to quite a few endogenous and exogenous pre-analytical factors, knowledge of these limitations is mandatory prior to clinical utilization since these variabilities complicate test result interpretation. Standardization to harmonize different assay methodologies is desired, and the primary aims of the IFCC/IOF bone marker standards working group are also presented. Current literature data advocate bone markers as best used in monitoring anti-osteoporosis therapy efficacy and compliance, nonetheless, there is abundant data supporting their role in predicting bone loss and fracture risk. Furthermore, they have widespread clinical utility in osteoporosis, renal osteodystrophy, and certain oncological conditions and rheumatic diseases.

BackgroundThe examination of peripheral blood is routinely used as a basic test in daily medical practice. Reliable reference intervals are necessary to avoid misdiagnoses, and the establishment of those intervals is an important task for clinical laboratories.The aim of the present study was to establish the reference intervals for complete blood count (CBC) on a Sysmex XN haematology analyser in healthy adults from the southern metropolitan area of Barcelona (Spain).MethodsA total of 213 apparently healthy adults who received a general health examination at Hospital Universitari de Bellvitge were recruited to this study. Blood samples collected in K3EDTA tubes were analysed on a Sysmex XN. Statistically relevant gender based partition was assessed, outliers removed, and the reference intervals calculated in concordance with Clinical and Laboratory Standards Institute (CLSI) EP28-A3C guidelines.ResultsThe CBC reference intervals were established in 191 adults (64 men and 127 women) who fulfilled all of the inclusion criteria. Significant gender-dependent differences in red blood cells, haematocrit, haemoglobin and platelets were found. The rest of the CBC reference intervals were obtained from the overall data.ConclusionsWe report CBC reference intervals established on a Sysmex XN analyser, a widely used automated analyser for which reference intervals were previously lacking in the literature. However, these reference intervals we recommend should be validated by individual laboratories for the local population as recommended by CLSI.

ObjectiveThe aim of the present study was to evaluate the possible association between the Q223R Leptin receptor (LEPR) polymorphism (A>G; rs1137101) and leptin levels in patients with rheumatoid arthritis (RA) from Western Mexico.MethodsA cross-sectional study was performed with 70 RA patients and 74 controls subject (CS). Disease activity was evaluated using DAS28 score, the Q223R LEPR polymorphism was determined by the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) and serum leptin levels, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and rheumatoid factor (RF) were quantified.ResultsRA patients had significant high serum leptin levels compared with CS; leptin levels correlated strongly with body composition measures, but not with inflammatory markers, disease evolution, and activity. The genotype and allele frequencies of the Q223R LEPR polymorphism were not associated with RA. Similarly, leptin levels did not differ between Q223R LEPR genotypes.ConclusionThe LEPR Q223R polymorphism was not associated with RA risk in patients from Mexican population, even though high levels of serum leptin were present and these could explain the low weight observed in RA patients when they were compared to control subjects. However, the serum leptin levels did not correlate with inflammatory markers, severity and disease evolution.

During the last decade, a lot of efforts has been made to improve the evaluation of renal functions. Measured Glomerular Filtration Rate (GFR) remains the only valuable test to confirm or confute the status of chronic kidney disease (CKD) and is recommended by Kidney Disease Global Outcomes guidelines when estimation of GFR is not reliable. However, in routine clinical practice, serum creatinine remains the one of the most prescribed biological parameters and is an undeniable factor, alone or in association with other parameters, of the estimation of GFR. Since many years, a great improvement in the creatinine measurements was realized because of the standardization of the methods and fabrication of an international standard with concentration near to physiological ones (SRM967). Standardization according to Isotopic Dilution Mass Spectrometry dramatically improves the analytical performances of creatinine assays resulting in a more accurate estimation of GFR using creatinine based equations. Indeed, the standardization of creatinine improves the analytical performance by reducing the bias and removing the influence of the interfering substances.However, biological variability of creatinine is not affected by analytical standardization and remains a limitation to the use of creatinine in some selected populations, having extreme ages or weights like children, elderly subjects, obese or malnourished populations. Standardization of creatinine assays result in a clear improvement of estimated GFR in general population but alternative methods should be used when creatinine production or metabolism is impaired.

[This corrects the article on p. 6 in vol. 28, PMID: 28439216.].

The assessment of the general inflammatory condition of patients with autoimmune connective tissue disorders (ACTD) is a major challenge. The use of traditional inflammatory markers including CRP-levels and erythrocyte sedimentation rate (ESR) is limited by several preanalytical factors and their low specificities. Soluble urokinase plasminogen activator receptor (suPAR) is one of the novel candidate markers that is increasingly used in immune mediated disorders. In our studies we compared suPAR levels of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and ankylosing spondylitis with those of healthy controls.suPAR provided valuable clinical information on disease activity in RA, SLE and SSc. We identified a subgroup of remitted RA patients, who presented still clinical symptoms of inflammatory activity which correlated to high plasma suPAR (while ESR and CRP were normal). In SLE we established specific suPAR cut-off values that support the discrimination between patients with high and those with moderate SLE activity. In patients with SSc suPAR correlated with objective measures of lung and other complications.In the majority of ACTDs including SLE, SSc or RA, suPAR is seemingly a good biomarker that would provide valuable clinical information. However, before the introduction of this novel parameter in laboratory repertoire important issues should be elucidated. These include the establishment of appropriate and disease specific cutoff values, clarification of interfering preanalytical values and underlying conditions and declaration of age- and gender-specific reference ranges.

At the start of the 21st century, a dramatic change occurred in the clinical laboratory community. Concepts from Metrology, the science of measurement, began to be more carefully applied to the in vitro diagnostic (IVD) community, that is, manufacturers. A new appreciation of calibrator traceability evolved. Although metrological traceability always existed, it was less detailed and formal. The In Vitro Diagnostics Directive (IVDD) of 2003 required manufacturers to provide traceability information, proving assays were anchored to internationally accepted reference materials and/or reference methods. The intent is to ensure comparability of patient test results, regardless of the analytical system used to generate them. Results of equivalent quality allows for the practical use of electronic health records (EHRs) capture a patient’s complete laboratory test history and allow healthcare providers to diagnose and treat patients, confident the test results are suitable for correct interpretation, i.e., are “fit for purpose” and reflect a real change in a patient’s condition and not just “analytical noise.” The healthcare benefits are obvious but harmonization of test systems poses significant challenges to the IVD Industry. Manufacturers must learn the theory of metrological traceability and apply it in a practical manner to assay calibration schemes. It’s difficult to effect such a practical application because clinical laboratories do not test purified analytes using reference measurement procedures but instead deal with complex patient samples, e.g., whole blood, serum, plasma, urine, etc., using “field methods.” Harmonization in the clinical laboratory is worth the effort to achieve optimal patient care.