The utility of serum amyloid A and other acute-phase reactants determination in ambulatory care COVID-19 patients.

Background: The unpredictable course of Coronavirus Disease 19 (COVID-19) is making good severity assessment tools crucial. This study aimed to assess the usefulness of serum amyloid A (SAA) and other acute-phase reactants (APRs) in ambulatory care COVID-19 patients and identified relationships between these markers and disease outcomes. Methods: From August to November 2020, patients seen in the outpatient department of the Clinic for Infectious and Tropical Diseases (Belgrade, Serbia) with confirmed COVID-19 were included. Patients were classified into mild, moderate, and severe disease groups based on World Health Organization criteria. SAA, C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT), ferritin, fibrinogen, D-dimer, albumin, and transferrin were measured. The median values of all APRs were compared between COVID-19 severity groups, hospitalized and non-hospitalized patients, and survivors and non-survivors. The Receiver operator characteristic (ROC) curve analysis was used for the classification characteristics assessment of individual APRs for the severity of illness, hospitalization, and survival.

Vitamin D Serum Levels and Vitamin D Receptor Genotype in Patients with Parkinson's Disease.

BACKGROUND: Vitamin D is a steroid hormone, known to be involved in the pathogenesis of various neurodegenerative disorders, including Parkinson's disease (PD). We aimed to clarify the relationship between hypovitaminosis D and the predisposition for PD and its clinical presentation. An additional aim was to examine the specific gene polymorphisms associated with vitamin D level. MATERIAL AND METHODS: Total level of 25(OH)-vitamin D (25(OH)D) was measured in the serum of parkinsonian patients (n = 113) and controls (n = 82) using a commercial immunoassay. Genetic analyses were performed using Taqman assays on Real Time PCR amplification system. RESULTS: Higher frequency of vitamin D deficiency (<50 nmol/L) was observed in PD patients, compared to controls (40.7% and 23.2%, respectively, P = 0.010). It was also a positive predictive marker of PD (OR, 2.27; 95% CI, 1.206-4.298; P < 0.011). Significantly higher UPDRS (35.85 ± 1.35 and 32.09 ± 0.99, respectively, P = 0.023) and HY scores (2(1.5-2.5) and 1.5(1.0-2.0), respectively, P = 0.005) were present in patients with 25(OH)D level < 50 nmol/L compared to patients with 25(OH)D level ≥ 50 nmol/L. Despite some trends observed, differences in allelic and genotypic distribution between controls and patients, as well as between subgroups, did not reach the level of significance (P > 0.05). CONCLUSIONS: Findings of this study confirm the hypothesis of a significant relationship between hypovitaminosis D and PD. We demonstrated higher prevalence of vitamin D deficiency in PD patients, as well as its predictive potential for the onset and progression of PD.

Comparison of the ELISA method with the nephelometric method for determination of serum amyloid A in patients with COVID 19.

This study aimed to examine the agreement of the serum amyloid A (SAA) values determined using the ELISA test and the nephelometric automated method. This study included 80 serum samples obtained from patients with COVID-19. Samples were determined using ELISA and the nephelometric method. Wilcoxon signed ranks test showed a statistically significant difference in the calculated median values (Z = -2.432, p = 0.015). The correlation between methods was statistically significant (r = 0.603, p < 0.0001). Bland Altman analysis showed a bias of 56.6 mg/L and a relative bias of 7.4% between the methods. The results of this study indicate that further studies are needed that will examine the compliance between the ELISA and the nephelometric method for determining SAA, and the results must be carefully interpreted based on the method used.

Antiphospholipid antibodies in healthy Serbian middle-aged subjects: Preliminary data.

Background: The investigation of the prevalence of the IgG and the IgM isotypes of anticardiolipin (aCL) and antib2glycoprotein I (ab2gpI) Abs in healthy Serbian middleaged subjects was the main goal of our study. In addition, we analyzed the potential associations of above-mentioned Abs with serum proteins and lipids/lipoproteins. Methods: Forty healthy subjects were included in our study. Obesity (BMI 30 kg/m2) was present in 8/40 (20%) subjects. Titers of analyzed Abs were measured by ELISA. Results: The prevalence of IgG and IgM ab2gpI Abs was 5% and 12.5%, respectively, while the prevalence of IgM aCL was 10%. The IgG ab2gpI Abs were significantly different between subjects with normal triglycerides levels and those with hypertriglyceridemia (Mann-Whitney, P = 0.014). The significant difference in hsCRP concentrations was observed between subjects with the increased levels of the IgM isotype of aCL Abs and those with normal IgM aCL values (Mann-Whitney, P = 0.028). Conclusions: Dyslipidemia and BMI ≥30 were associated with aPL Abs and therefore, the correction of BMI and lipid status might be beneficial in reduction or elimination of predisposing factors that might trigger thrombotic events in otherwise healthy middle-aged subjects. Larger national study is necessary to confirm our findings.

Magnesium supplementation and iron status among female students: The intervention study.

Background: Literature data indicate the benefit of magnesium (Mg) supplementation. The aim of this study was to examine the effect of short-term Mg supplementation on iron status in healthy female participants. Methods: One hundred healthy female students of the University of Belgrade - Faculty of Pharmacy participated the study during eleven intervention days. Students ingested Mg preparations with the same dose of the active substance. The analysis included the measurement of serum iron, unsaturated iron binding capacity (UIBC), total iron binding capacity (TIBC), total Mg (tMg), ionized Mg (iMg), complete blood count, met-, carboxyand oxy-haemoglobin (metHgb, COHgb, O2Hgb). Transferrin concentrations and percentage of transferrin saturation (SAT) were calculated manually. The association among the analyzed biochemical parameters was examined using polynomial regression. A principal component analysis (PCA) was used for the evaluation of interdependence between the analyzed parameters. Results: A statistically significant trend for change in O2Hgb (%) by tertiles of iMg concentrations was found (P = 0.029). Serum tMg reached significant positive correlation with the SAT at concentration levels greater than 0.9 mmol/L, after 11 days of intervention (R2=0.116). Ionized Mg in a concentration higher than 0.6 mmol/L is positively correlated with SAT and serum Fe (R2=0.214; 0.199, respectively). PCA revealed variability of 64.7% for two axes after 11 days. Conclusions: Mg supplementation leads to an improvement in the certain iron status parameters even in individuals with optimal levels of these indices. However, caution should be exercised when supplementing Mg, and laboratory monitoring of the interaction is required.

Integrating moving average control procedures into the risk-based quality control plan in small-volume medical laboratories.

Introduction: The modern approach to quality control (QC) in medical laboratories implies the development of a risk-based control plan. This paper aims to develop a risk-based QC plan for a laboratory with a small daily testing volume and to integrate the already optimized moving average (MA) control procedures into this plan. Materials and methods: A multistage bracketed QC plan for ten clinical chemistry analytes was made using a Westgard QC frequency calculator. Previously, MA procedures were optimized by the bias detection simulation method. Results: Aspartate aminotransferase, HDL-cholesterol and potassium had patient-risk sigma metrics greater than 6, albumin and cholesterol greater than 5, creatinine, chlorides, calcium and total proteins between 4 and 5, and sodium less than 4. Based on the calculated run sizes and characteristics of optimized MA procedures, for 6 tests, it was possible to replace the monitoring QC procedure with an MA procedure. For the remaining 4 tests, it was necessary to keep the monitoring QC procedure and introduce MA control for added security. Conclusion: This study showed that even in a laboratory with a small volume of daily testing, it is possible to make a risk-based QC plan and integrate MA control procedures into that plan.

Sensitivity of three thyrotropin receptor antibody assays in thyroid-associated orbitopathy.

Background: Thyrotropin receptor autoantibodies (TSH-RAb) are indispensable biomarkers in the laboratory assessment of thyroid-associated orbitopathy (TAO). Clinical sensitivity of three different assays for TSH-R-Ab determination was evaluated in patients with TAO. Methods: 87 consecutive TAO patients were enrolled and their serum samples analyzed in parallel with three assays. An ECLIA competitive binding and a chemiluminescent bridge immunoassay were used to measure total and binding TSH-R-Ab concentration, while their functional activity was determined using a stimulatory TSH-R-Ab (TSAb) cellbased bioassay. Results: Compared to the two binding assays (ECLIA p<0.001, bridge p=0.003), the TSAb bioassay was more sensitive pertaining to the positive detection of TSH-R-Ab in TAO patients. No difference (p=0.057) was noted between the ECLIA and bridge assays regarding sensitivity rate. All patients with active and/or moderate-to-severe TAO tested positive in the TSAb bioassay (100% and 100%, respectively), while the positivity rates for bridge and ECLIA binding assays were 89.7% and 82.1% for active TAO, and 90.2% and 86.3% for severe TAO, respectively. Negative predictive values of the bioassay, bridge, and ECLIA assays were 100%, 75%, and 71%, respectively for active TAO, and 100%, 86%, and 71%, respectively for moderate-to-severe TAO. The superiority of the bioassay was most prominent in euthyroid (ET) TAO. Positivity rates of the TSAb bioassay, bridge and ECLIA binding assays were 89.6%, 75%, and 64.6%, respectively for inactive TAO; 86.1%, 69.4%, and 52.8%, respectively for mild TAO; 87.5%, 62.5%, and 12.5%, respectively for euthyroid TAO. The bridge assay correlated better with the ECLIA binding assay (r=0.893, p<0.001), compared to the bioassay (r=0.669, p<0.001). Conclusions: In patients with TAO of various activity and severity, the TSAb bioassay demonstrates a superior clinical performance compared to both ECLIA and bridge binding assays.

Effects of short-term magnesium supplementation on ionized, total magnesium and other relevant electrolytes levels.

This study aimed to investigate the short-term effects of three magnesium (Mg) dietary supplements containing mineral immediately available for absorption on Mg biochemical status indices (ionized and total Mg), as well as their effects on electrolytes levels in healthy female young adults (n = 61). After a 10-days intervention period supplementation with powder/granulate containing Mg oxide led to an increase in both ionized Mg concentration and % in total Mg in comparison with the baseline. Supplementation with Mg citrate was associated with the significant increase in % of ionized fraction and decrease in serum total Mg concentration. By contrast, among participants consuming Mg carbonate in the form of effervescent tablets ionized Mg concentration and % in total Mg decreased, without detectable changes in serum total Mg. In conclusion, after the short-term supplementation period, Mg oxide demonstrated superior bioavailability compared to the other examined Mg supplements without affecting other minerals' levels.

Overweight and obesity in polycystic ovary syndrome: association with inflammation, oxidative stress and dyslipidaemia.

Polycystic ovary syndrome (PCOS) is associated with altered lipid profile and increased small, dense LDL particles (sdLDL). Considering that paraoxonase 1 (PON1) is an antioxidative enzyme located on HDL particles, the aim of this study was to investigate the connection between oxidative stress (OS) and PON1 activity with lipoprotein subclasses in PCOS depending on obesity. In 115 PCOS patients, lipoprotein subclasses distributions were determined by gradient gel electrophoresis. OS status was assessed by total oxidative status (TOS), advanced oxidation protein products, malondialdehyde (MDA), prooxidant-antioxidant balance (PAB), total antioxidative status (TAS) and superoxide dismutase (SOD) and PON1 activity. Overweight/obese PCOS patients (n 55) had increased OS compared with normal weight patients (n 60). In addition, overweight/obese group had lower HDL size and higher proportion of HDL 3a subclasses (P < 0·05). PAB was in negative correlation with HDL 2a (P < 0·001), whereas MDA and SOD correlated positively with HDL 3 subclasses (P < 0·05). Serum PON1 activity was positively associated with proportions of PON1 activity on HDL 2b (P < 0·05) and 2a (P < 0·01), but negatively with the proportion on HDL 3 particles (P < 0·01). LDL B phenotype patients had increased TAS, SOD and PON1 activity on HDL 2b, but decreased PON1 activity on HDL 3 subclasses. OS is associated with altered lipoprotein subclasses distribution in PCOS patients. Obesity in PCOS affects the profile of HDL subclasses, reflected through the reduced proportion of PON1 activity on HDL 3 subclasses in the presence of sdLDL particles.

Moving average procedures as an additional tool for real-time analytical quality control: challenges and opportunities of implementation in small-volume medical laboratories.

INTRODUCTION: Moving average (MA) is one possible way to use patient results for analytical quality control in medical laboratories. The aims of this study were to: (1) implement previously optimized MA procedures for 10 clinical chemistry analytes into the laboratory information system (LIS); (2) monitor their performance as a real-time quality control tool, and (3) define an algorithm for MA alarm management in a small-volume laboratory to suit the specific laboratory. MATERIALS AND METHODS: Moving average alarms were monitored and analysed over a period of 6 months on all patient results (total of 73,059) obtained for 10 clinical chemistry parameters. The optimal MA procedures were selected previously using an already described technique called the bias detection simulation method, considering the ability of bias detection the size of total allowable error as the key parameter for optimization. RESULTS: During 6 months, 17 MA alarms were registered, which is 0.023% of the total number of generated MA values. In 65% of cases, their cause was of pre-analytical origin, in 12% of analytical origin, and in 23% the cause was not found. The highest alarm rate was determined on sodium (0.10%), and the lowest on calcium and chloride. CONCLUSIONS: This paper showed that even in a small-volume laboratory, previously optimized MA procedures could be successfully implemented in the LIS and used for continuous quality control. Review of patient results, re-analysis of samples from the stable period, analysis of internal quality control samples and assessment of the analyser malfunctions and maintenance log have been proposed for the algorithm for managing MA alarms.

Antiphospholipid antibodies in patients with Graves' orbitopathy: preliminary data.

PURPOSE: Graves' orbitopathy (GO) is an inflammatory autoimmune disorder of the orbit and while the antiphospholipid antibodies (aPL) Abs were associated with the markers of inflammation in the antiphospholipid syndrome (APS), there is no literature that investigate the presence of aPL Abs in GO. We analyzed the prevalence of aPL Abs and the differences between aPL (+) and aPL (-) subgroups of GO patients. METHODS: Study included consecutive patients with GO (66 with Graves' (GD), 10 with Hashimoto (HD), and 8 were euthyroid). Anticardiolipin (aCL) and anti-beta 2glycoprotein I (aß2gpI) Abs were measured by ELISA. RESULTS: aPL Abs were present in 9/84 (10.71%) patients. The IgM aß2gpI Abs were present in 8/66 and in 1/10 patients with GD and HD. The IgG aCL Abs were present in one GD patient, and IgM aCL were present in 3/66 GD and in 1/10 patients with HD. In GD group, anti-Tg Abs were in positive correlation with aß2gpI IgG (p = 0.000) and with anti-TPO Abs (p = 0.016). In HD group, anti-Tg Abs were in positive correlation with IgM aCL (p = 0.042), while anti-TPO Abs were in positive correlation with aß2gpI IgM (p = 0.014). CONCLUSION: This study is the first report of the aPL Abs presence in GO patients. The anti-thyroid Abs were linked to aPL suggesting that their presence is not the sole consequence of hyperstimulation of autoreactive B-lymphocytes. Larger studies are necessary to confirm potential cause-effect relations.

Alpha-melanocyte-stimulating hormone during exercise recovery has prognostic value for coronary artery disease.

PURPOSE: Alpha-melanocyte-stimulating hormone (alpha-MSH) has proven cardiovascular effects and plays a significant role as an endogenous countermeasure to ischemia-reperfusion injury. The aim of the current study was to examine the response of alpha-MSH during exercise in patients diagnosed with coronary artery disease (CAD) and evaluate its value in the assessment of severity and prognosis. METHODS: Forty subjects with documented CAD (i.e., lesions on coronary angiography ≥ 50%) were included. Cardiopulmonary exercise testing (CPET) on a treadmill (TM) and recumbent ergometer (RE) were performed on two visits, 2-4 days apart, during 2 months of coronary angiography; subsequently, the subjects were followed up for 32 ± 10 months. At rest, at peak CPET, and after 3 min of recovery, plasma levels of alpha-MSH were measured by enzyme-linked immunosorbent assay technique. RESULTS: Mean ejection fraction was 56.7 ± 9.6%. Alpha-MSH similarly increased from rest to peak CPET on both modalities. There were no significant differences in alpha-MSH values during testing in patients with 1,2- and 3-vesel CAD, nor in patients with a SYNTAX score 0.05). Among CPET and hormonal parameters, ∆alpha-MSH recovery/peak during RE CPET was the best predictor of cardiac event occurrence (chi-square 6.67, HR = 0.51, CI = 0.25-1.02, p = 0.010). CONCLUSION: ∆alpha-MSH recovery/peak during RE CPET has predictive value for CAD prognosis, demonstrating involvement of alpha-MSH in CAD and a link between stress hormones and cardiac events.

Measurement uncertainty as a universal concept: can it be universally applicable in routine laboratory practice?

Measurement uncertainty (MU) of results is one of the basic recommended and accepted statistical methods in laboratory medicine, with which analytical and clinical evaluation of laboratory test quality is assessed. Literature data indicate that the calculation of MU is not a simple process, but that its assessment in daily laboratory practice should be reduced to routine and simple presentation, understandable to both laboratory professionals and physicians. In order to achieve this, it is necessary to understand the purpose of the test for which MU is to be determined. Various suggestions have been given for presentation of MU as a quantitative indicator of the quality of the final measurement result in the medical laboratory. Although MU refers to the final measurement result, this metrological concept reflects the entire laboratory measurement process. The data on estimated MU is used to interpret the measured numerical result, and represents quantitatively the quality of the measurement itself, i.e. how different are the results of multiple measurements of the analyte of interest in the same sample, as well as whether the method of determination itself is subjected to significant random and systematic deviation. Initially, in the metrological concept, the MU is viewed in relation to the true value of the analyte of interest. However, the true value of the analyte measured in the biological fluid matrix of the study population cannot be known. It is therefore considered the closest value obtained by the perfect method, for which the bias and inaccuracy, as measures of systematic and random error, are equal to zero, which is practically impossible to achieve in routine laboratory practice. Although current standards require accredited medical laboratories to estimate MU, none of these guidelines provide clear guidance on how this can be achieved in daily laboratory work. This review examines literary data and documents dealing with MU issues, but also highlights what additional terms and data should be considered when interpreting MU. This paper ultimately draws attention, and once again points out, that a simpler solution is needed for this universal concept to be formally and universally applicable in routine laboratory medicine practice.

Lipid status association with 25-hydroxy vitamin D: Cross sectional study of end stage renal disease patients.

BACKGROUND: Some observational studies indicate an association of 25-hydroxy vitamin D (25(OH)D) insufficiency and atherogenic cholesterol concentrations. The aim of this study was to investigate relationship between 25(OH)D concentrations and lipid parameters in end stage renal disease (ESRD) patients, separately for predialysis, hemodialysis and peritoneal dialysis patients. METHODS: We have adjusted 25(OH)D concentrations for seasonal variability with cosinor analysis, and performed all further analysis using these corrected 25(OH)D concentrations. Concentrations of 25(OH)D and the lipid parameters were determined in 214 ESRD patients and 50 control group participants. The analysis included the measurement of 25(OH)D by HPLC, apolipoprotein (Apo) AI, ApoB and Lp(a) by nephelometry, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) by spectrophotometry and manually calculated ApoB/ApoAI and LDL-C/HDL-C ratio. RESULTS: ESRD patients with adjusted 25(OH)D concentrations of 50 nmol/L had significantly higher TC (P = 0.005) and ApoAI (P = 0.049). Significantly higher HDLC (P = 0.011) and ApoAI (P = 0.020) were found in hemodialysis patients with the 25(OH)D concentrations of 50 nmol/L. The other analyzed lipid parameters differed significantly between predialysis, hemodialysis and peritoneal dialysis patients with 25(OH)D concentrations of < 50 nmol/L. CONCLUSIONS: Our study indicate the significant relationship between 25(OH)D repletion and optimal concentrations of lipid parameters in ESRD patients. Further research is necessary to explain whether joint evaluation of vitamin D status and lipid abnormalities could improve cardiovascular outcome in ESRD patients.

Comparison between bone alkaline phosphatase immunoassay and electrophoresis technique in hemodialysis patients.

BACKGROUND: Problem of the variability between the different methods using for bone alkaline phosphatase (bALP) determination greately influences the clinical significance of bALP as direct marker of bone metabolism. The aim of this study was to compare immunoassay with electrophoresis technique for bALP determination. METHODS: We measured bALP in 71 patients on hemo - dialysis with agar gel electrophoresis (ISO-PAL, SEBIA) and immunoassay (OSTASE, Beckman Coulter). RESULTS: The analyzed methods showed significant correlation (Spearman's rho: 0.776, P < 0.01), but we found statistically significant (P < 0.01) positive bias (27%) for the results measured by immunoassay. In support of this, using electrophoresis technique we have detected presence of the intestinal isoenzymes of alkaline phosphatase in 55% of patients with median value of 30% of the total alkaline phoshatase and presence of liver-2 alkaline phosphatase isoform in 42% of patients with median value of 16.6%. The Kendall's W of 0.787 (P<0.0001) revealed significant concordance between two analysed methods. Cusum test showed no significant deviation from linearity (P=0.850). CONCLUSIONS: Despite good agreement between immuno - assay methods and electrophoresis technique for bALP determination, interchangeability between these two methods is questionable. Although immunoassays are increasingly used, as fully automated methods, in a large number of laboratories and become routine methods for bALP determination, it should be beared in mind, besides various interferences, also the heterogeneity of the bALP itself, especially in patients on hemodialysis.

In vivo toxicity evaluation of two polyoxotungstates with potential antidiabetic activity using Wistar rats as a model system.

In this study, the in vivo hypoglycemic effect of a donut-shaped polyanion salt (NH4)14[Na@P5W30O110]·31H2O {NaP5W30} and its Ag-containing derivative K14[Ag@P5W30O110]·22H2O·6KCl {AgP5W30}, as well as their hepatotoxicity and nephrotoxicity, was evaluated. In the screening hypoglycemic study, Wistar albino rats with streptozotocin induced diabetes were treated intraperitoneally with three single doses (5, 10, and 20 mg per kg per b.w.) of both investigated polyoxotungstates. The blood glucose levels, measured before and after 2, 4 and 6 h polyoxotungstate application, showed that both studied compounds induced the most pronounced and time dependent glucose lowering effects at the doses of 20 mg kg-1. Thus, daily doses of 20 mg kg-1 were administered to Wistar albino rats orally for 14 days in further toxicity examinations. The serum glucose concentration and biochemical parameters of kidney and liver function, as well as a histopathological analysis of kidney and liver tissues were evaluated 14 days after the polyoxotungstate administration. Both investigated compounds did not induce statistically significant alterations of the serum glucose and uric acid concentrations, as well as some of the liver function markers (serum alanine and aspartate aminotransferases, and alkaline phosphatase activities). However, the significant decrease in serum total protein and albumin concentrations and the increase in biochemical parameters of renal function - serum urea (up to 63.1%) and creatinine concentrations (up to 23.3%) were observed for both polyoxotungstates. In addition, the detected biochemical changes were in accordance with kidney and liver histhopathological analysis. Accordingly, the hepatotoxic and nephrotoxic effects of these potential antidiabetic polyoxotungstates could be considered as mild.

Optimizing moving average control procedures for small-volume laboratories: can it be done?

INTRODUCTION: Moving average (MA) means calculating the average value from a set of patient results and further using that value for analytical quality control purposes. The aim of this study was to examine whether the selection, optimization and validation of MA procedures can be performed using the already described bias detection simulation method and whether it is possible to select appropriate MA procedures for a laboratory with a small daily testing volume. MATERIALS AND METHODS: The study was done on four analytes: creatinine, potassium, sodium and albumin. All patient results of these tests processed during six months were taken from the laboratory information system. Using the MA Generator software, different MA procedures were analysed. Different inclusion criteria, calculation formulas, batch sizes and weighting factors were tested. Selection of optimal MA procedures was based on their ability to detect simulated biases of different sizes. After optimization, the validation of MA procedures was done. The results were presented by bias detection curves and MA validation charts. RESULTS: Simple MA procedures for albumin and sodium without truncation limits were selected as optimal. Exponentially weighted MA procedures were found optimal for creatinine and potassium, with the upper truncation limits of 150 µmol/L and 6 mmol/L, respectively. CONCLUSIONS: It has been experimentally confirmed that it is possible to perform the selection, optimization and validation of MA procedures using the bias detection simulation method. Also, it is possible to define MA procedures optimal for a laboratory with a small daily testing volume.

Adiponectin: a therapeutic target in the antiphospholipid syndrome?

The antiphospholipid syndrome (APS) is an autoimmune disease characterized by the presence of the IgG and/or IgM isotypes of the antiphospholipid antibodies, thrombosis and/or recurrent pregnancy losses. Various markers of inflammation are associated with clinical and/or laboratory features of APS. Adiponectin (Ad) is a member of the adipocytokines that exert its roles by binding to its receptors (AdR). Peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonists induced Ad production. The aged Pparg null-mice represented the first animal model that spontaneously develops APS and this model emphasized the importance of PPAR-gamma signaling in the development of APS. Recombinant Ad (rAd) application was beneficial for the improvement of glucose, insulin and lipid levels in mice. Orally active AdR agonist exerted similar effects to Ad in mice. Due to the re-occurrence of thrombotic episodes in APS patients (despite life-long anticoagulation), administration of PPAR-gamma agonists, rAd, or AdR agonists should be further tested in experimental models of APS, which eventually, will provide more data for novel therapeutic strategies that will ameliorate clinical manifestations of the APS.

Uncertainty of Measurement in Laboratory Medicine.

An adequate assessment of the measurement uncertainty in a laboratory medicine is one of the most important factors for a reliable interpretation of the results. A large number of standards and guidelines indicate the need for a proper assessment of the uncertainty of measurement results in routine laboratory practice. The available documents generally recommend participation in the proficiency schemes/ external quality control, as well as the internal quality control, in order to primarily verify the quality performance of the method. Although all documents meet the requirements of the International Standard, ISO 15189, the standard itself does not clearly define the method by which the measurement results need to be assessed and there is no harmonization in practice regarding to this. Also, the uncertainty of measurement results is the data relating to the measured result itself, but all factors that influence the interpretation of the measured value, which is ultimately used for diagnosis and monitoring of the patient's treatment, should be taken into account. So in laboratory medicine, an appropriate assessment of the uncertainty of the measurement results should have the ultimate goal of reducing diagnostic uncertainty. However, good professional laboratory practice and understanding analytical aspects of the test for each individual laboratory is necessary to adequately define the uncertainty of measurement results for specific laboratory tests, which helps to implement good clinical practice. Also, setting diagnoses in medicine is a decision with a certain degree of uncertainty, rather than statistically and mathematically calculated conclusion.

Evaluation of a Summary Score for Dyslipidemia, Oxidative Stress and Inflammation (the Doi Score) in Women with Polycystic Ovary Syndrome and its Relationship with Obesity.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a cardiometabolic disorder whose features include dyslipidemia, increased oxidative stress (OS, oxy) and chronic inflammation. The aim of this study was to investigate the ability of a summary score for dyslipidemia, OS and inflammation (the DOI score) to discriminate PCOS patients from healthy individuals and to evaluate the effect of obesity on individual scores and the DOI score in patients. METHODS: Lipid status parameters, OS status parameters (advanced oxidation protein products; total oxidative status; prooxidant-antioxidant balance; malondialdehyde; total protein sulphydryl groups and paraoxonase 1 activity) and CRP were measured in 114 patients and 50 controls using standardised assays. The DOI score was calculated as the sum of dyslipidemia, oxy and inflammation scores, determined as Z-score values for every subject in relation to the controls. RESULTS: PCOS patients had significantly higher oxy-score compared to controls (P<0.001). In addition, the DOI score was significantly higher in PCOS patients (P<0.001) as the dyslipidemia (P<0.05) and inflammatory scores (P<0.001) were greater. According to ROC analysis, the oxy-score showed better diagnostic accuracy in discriminating PCOS patients compared to the DOI score (AUC>0.9, P<0.01). Furthermore, obesity affected the risk scores in patients, especially the DOI score (significantly higher DOI scores in such patients, P<0.001). CONCLUSION: PCOS patients had greater dyslipidemia, chronic inflammation and OS compared to controls and could be segregated using all four scores. Our data suggest that weight gain could be the common factor responsible for induction and propagation of dyslipidemia, OS and inflammation in PCOS patients.