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The transformation of clinical laboratories towards digitalization requires processes that improve digital maturity. This requires establishing connectivity, end-to-end workflow, and advanced analytical technologies and techniques. Digital technologies have the key role here, directing laboratory personnel and scientists to move their focus from routine to more complex and meaningful work. This requires their empowerment in working with new instruments and software. Strategies leading clinical laboratories through this transformation are not without challenges, but different models are being developed to overcome them. The essential is the role of interoperability.

ObjectivesTo evaluate the potential of soluble cluster of differentiation 146 (sCD146) in the detection and grading of congestion in patients with acute dyspnoea.DesignSubanalysis of the prospective observational Lithuanian Echocardiography Study of Dyspnoea in Acute Settings (LEDA) cohort.SettingTwo Lithuanian university centres.ParticipantsAdult patients with acute dyspnoea admitted to the emergency department.MethodsCongestion was assessed using clinical and sonographic parameters. All patients underwent sCD146 and N-terminal pro-B-type natriuretic peptide (NT-proBNP) testing.ResultsThe median value of sCD146 concentration in the study cohort (n=437) was 405 (IQR 315–509) ng/mL. sCD146 was higher in patients with peripheral oedema than in those without (median (IQR) 472 (373–535) vs 400 (304–501) ng/mL, p=0.009) and with pulmonary rales than in those without (439 (335–528) vs 394 (296–484) ng/mL, p=0.001). We found a parallel increase of estimated right atrial pressure (eRAP) and sCD146 concentration: sCD146 was 337 (300–425), 404 (290–489) and 477 (363–572) ng/mL in patients with normal, moderately elevated and high eRAP, respectively (p=0.001). In patients with low NT-proBNP, high sCD146 distinguished a subgroup with a higher prevalence of oedema as compared with patients with low levels of both biomarkers (76.0% vs 41.0%, p=0.010). Moreover, high sCD146 indicated a higher prevalence of elevated eRAP, irrespective of NT-proBNP concentration (pConclusionsCD146 concentration reflects the degree of intravascular and tissue congestion assessed by clinical and echocardiographic indices, with this association maintained in patients with low NT-proBNP. Our data support the notion that NT-proBNP might represent heart stretch while sCD146 rather represents peripheral venous congestion.

High-sensitivity troponin assay brought new challenges as we detect elevated concentration in many other diseases, and it became difficult to distinguish the real cause of this elevation. In this notion, diagnosis of acute coronary syndrome (ACS) remains a challenge in emergency department (ED). We aim to examine different approaches for rule-in and rule-out of ACS using risk scores, copeptin, and coronary computed tomography angiography (CCTA). A prospective observational study was designed to evaluate chest pain patients. Consecutive adult patients admitted to the ED with a chief complaint of chest pain due to any cause were included. All patients were followed-up for 6 months after discharge for major adverse cardiovascular events and readmissions. Admission data, ED processes, and diagnoses were analyzed. One hundred forty-six patients were included, average age was 63 ± 13.4 years, and 95 (65.1%) were male. Global Registry of Acute Coronary Events (GRACE) and History, ECG, Age, Risk factors, Troponin (HEART) scores showed good prognostic abilities, but HEART combination with copeptin improves diagnoses of myocardial infarction (area under the curve [AUC] 0.764 vs AUC 0.864 P = .0008). Patients with elevated copeptin were older, had higher risk scores, and were more likely to be admitted to hospital and diagnosed with ACS in ED. For copeptin, AUC was 0.715 (95% confidence interval 0.629-0.803), and for combination with troponin, AUC of 0.770 (0.703-0.855) did not improve rule-in of myocardial infarction. High-sensitivity troponin I assay alongside prior stroke, history of carotid stenosis, dyslipidemia, use of diuretics, and electrocardiogram changes (left bundle branch block or ST depression) are good predictors of myocardial infarction (χ² = 52.29, AUC = 0.875 [0.813-0.937], P < .001). The regression analysis showed that combination of copeptin and CCTA without significant stenosis can be used for ACS rule-out (χ² = 26.36, P < .001, AUC = 0.772 [0.681-0.863], negative predictive value of 96.25%). For rule-in of ACS, practitioner should consider not only scores for risk stratification but carefully analyze medical history and nonspecific electrocardiogram changes and even with normal troponin results, we strongly suggest thorough evaluation in chest pain unit. For rule-out of ACS combination of copeptin and CCTA holds great potential.

European Union (EU) Directive 2013/55/EC (The Recognition of Professional Qualifications) allows Member States to decide on a common set of minimum knowledge, skills and competences that are needed to pursue a given profession through a Common Training Framework. To be adopted the framework must combine the knowledge, skills and competences of at least one third of the Member States. Professionals who have gained their qualifications under a Common Training Framework will be able to have these recognised automatically within the Union. The backbone of the European Federation of Clinical Chemistry and Laboratory Medicine’s (EFLM) proposed Common Training Framework for non-medical Specialists in Laboratory Medicine is outlined here. It is based on an Equivalence of Standards in education, training, qualifications, knowledge, skills, competences and the professional conduct associated with specialist practice. In proposing the recognition of specialist practice EFLM has identified 15 EU Member States able to meet Equivalence and in whom the profession and/or its training is regulated (an additional EU Commission requirement). The framework supports and contributes to the Directive’s enabling goals for increasing professional mobility, safeguarding consumers and ensuring a more equitable distribution of skills and expertise across the Member States. It represents EFLM’s position statement and provides a template for professional societies and/or competent authorities to engage with the EU Commission.

Background. To evaluate the diagnostic potential of [-2] proPSA (p2PSA), %p2PSA, Prostate Health Index (phi), and phi density (PHID) as independent biomarkers and in composition of multivariable models in predicting high-grade prostatic intraepithelial neoplasia (HGPIN) and overall and clinically significant prostate cancer (PCa). Methods. 210 males scheduled for prostate biopsy with total PSA (tPSA) range 2-10 ng/mL and normal digital rectal examination were enrolled in the prospective study. Blood samples to measure tPSA, free PSA (fPSA), and p2PSA were collected immediately before 12-core prostate biopsy. Clinically significant PCa definition was based on Epstein’s criteria or ISUP grade≥2 at biopsy. Results. PCa has been diagnosed in 112 (53.3%) patients. Epstein significant and ISUP grade≥2 PCa have been identified in 81 (72.3%) and 40 (35.7%) patients, respectively. Isolated HGPIN at biopsy have been identified in 24 (11.4%) patients. Higher p2PSA and its derivative mean values were associated with PCa. At 90% sensitivity, PHID with cut-off value of 0.54 have demonstrated the highest sensitivity of 35.7% for overall PCa detection, so PHID and phi with cut-off values of 33.2 and 0.63 have demonstrated the specificity of 34.7% and 34.1% for ISUP grade≥2 PCa detection at biopsy, respectively. In univariate ROC analysis, PHID with AUC of 0.77 and 0.80 was the most accurate predictor of overall and Epstein significant PCa, respectively, so phi with AUC of 0.77 was the most accurate predictor of ISUP grade≥2 PCa at biopsy. In multivariate logistic regression analysis, phi improved diagnostic accuracy of multivariable models by 5% in predicting ISUP grade≥2 PCa. Conclusions. PHID and phi have shown the greatest specificity at 90% sensitivity in predicting overall and clinically significant PCa and would lead to significantly avoid unnecessary biopsies. PHID is the most accurate predictor of overall and Epstein significant PCa, so phi is the most accurate predictor of ISUP grade≥2 PCa. phi significantly improves the diagnostic accuracy of multivariable models in predicting ISUP grade≥2 PCa.

The role of parvovirus B19 (PVB19) in the pathogenesis of idiopathic dilated cardiomyopathy (DCM) remains poorly understood. Therefore, we have measured the levels of inflammation, fibrosis, apoptosis, and necrosis in endomyocardial biopsies (EMBs) and sera of nonischemic PVB19-positive (n = 14) and PVB19-negative (n = 18) DCM patients. Chronic persistence of PVB19 in myocardium did not induce significant infiltration of T cells (CD3 and CD45Ro) and macrophages (CD68), and did not secrete TNFα, IL-6, and CRB. The fibrosis in PVB19-positive EMBs was also lower compared to the virus-negative ones, while ECM degrading matrix metalloproteinase MMP1 and gelatinase MMP2 were significantly (by twofold) upregulated. In addition, there was no activation of neither apoptotic nor necrotic pathways. However, levels of antiapoptotic mitochondrial Bcl-2 and heat shock protein 60 (Hsp60) in PVB19-positive biopsies were almost threefold lower than in PVB19-negative ones revealing impairment of mitochondria. Altogether, data indicate that persistence of PVB19 in myocardiums of nonischemic DCM patients can cause myocardial ECM remodeling through the MMPs, such as MMP1 and MMP2, and mitochondrial impairment. The correlative analysis of measured biomarkers suggested likely further activation of apoptotic cell death pathways rather than fibrosis. Data also suggest that antiviral therapy could be beneficial for PVB19-positive DCM patients by managing further pathological myocardial remodeling.

Background: Rheumatoid arthritis (RA) is an autoimmune inflammatory disease with complex etiopathogenesis launched by multiple risk factors, including epigenetic alterations. RA is possibly linked to vitamin D that is epigenetically active and may alter DNA methylation of certain genes. Therefore, the study aimed to evaluate the relationship between DNA methylation status of vitamin D signaling pathway genes (VDR, CYP24A1, CYP2R1), vitamin D level and associations with RA.Materials and Methods: Totally 76 participants (35 RA patients and 41 healthy controls) were enrolled from a case-control vitamin D and VDR gene polymorphisms study regarding age and vitamin D concentration. CpG islands in promoter regions of the VDR, CYP24A1, CYP2R1 genes were chosen for DNA methylation analysis by means of pyrosequencing. Chemiluminescent microplate immunoassay was used to assess 25(OH)D serum levels. RA clinical data, i.e. the disease activity score C-reactive protein 28 (DAS28 – CRP) as well as patient-reported outcome questionnaires were recorded.Results: The study showed similar methylation pattern in the promoter regions of vitamin D pathway genes in RA and control group with p>0.05 (VDR gene 2.39% vs. 2.48%, CYP24A1 gene 16.02% vs. 15.17% and CYP2R1 2.53% vs. 2.41%). CYP24A1 methylation intensity was significantly higher in compare to methylation intensity of VDR and CYP2R1 genes in both groups (p0.05). A significantly higher CYP24A1 methylation intensity (p=0.0104) was detected in blood cells of vitamin D deficient (

Objectives Medical laboratories may, at their own discretion, exceed but not undercut regulatory quality requirements. Available economic resources, however, may drive or hinder eagerness to exceed minimum requirements. Depending on the respective scopes of regulatory and economic framework conditions, differing levels of quality efforts to safeguard laboratory performance can be anticipated. However, this has not yet been investigated. Methods Immunohaematology external quality assessment (EQA) results collected by 26 EQA providers from their participant laboratories in 73 countries from 2004 to 2019 were evaluated. Error rates were aggregated in groups according to the respective national regulatory and economic framework conditions, to whether or not expert advice was provided in case of incorrect results, and the frequency of EQA samples. Results These representative data indicate no association between national regulatory (mandatory participation in EQA, monitoring of performance of individual laboratories by authorities, financial consequences of incorrect results) and economic (level of national income, share of national health expenditure) conditions to the quality performance of medical laboratories in immunohaematology. However, EQA providers’ support for laboratories in the event of incorrect results appear to be associated with lower error rates, but a high EQA sample frequency with higher error rates. Conclusions Further research into the impact of introducing or changing services of EQA providers is needed to confirm the results found in this first of its kind study.

Inflammation-related biomarkers are associated with clinical outcomes in mixed-etiology chronic heart failure populations. Inflammation-related markers tend to be higher in ischemic than in non-ischemic dilated cardiomyopathy (NI-DCM) patients, which might impact their prognostic performance in NI-DCM patients. Therefore, we aimed to assess the association of inflammation-related biomarkers with heart failure severity parameters and adverse cardiac events in a pure NI-DCM patient cohort. Fifty-seven patients with NI-DCM underwent endomyocardial biopsy. Biopsies were evaluated by immunohistochemistry for CD3+, CD45ro+, CD68+, CD4+, CD54+, and HLA-DR+ cells. Blood samples were tested for high-sensitivity C-reactive protein (hs-CRP), interleukin-6, tumor necrosis factor-α (TNF-α), soluble urokinase-type plasminogen activator receptor and adiponectin. During a five-year follow-up, twenty-seven patients experienced at least one composite adverse cardiac event: left ventricle assist device implantation, heart transplantation or death. Interleukin-6, TNF-α and adiponectin correlated with heart failure severity parameters. Patients with higher levels of interleukin-6, TNF-α, adiponectin or hs-CRP, or a higher number of CD3+ or CD45ro+ cells, had lower survival rates. Interleukin-6, adiponectin, and CD45ro+ cells were independently associated with poor clinical outcomes. All patients who had interleukin-6, TNF-α and adiponectin concentrations above the threshold experienced an adverse cardiac event. Therefore, a combination of these cytokines can identify high-risk NI-DCM patients.

Background and Objectives: Kidney transplant recipients represent a unique population with metabolic abnormalities, altered nutritional and immune status, as well as an imbalanced regulation of adipocytokine metabolism. Leptin is a hormonally active protein mainly produced by fat tissue that modulates appetite, satiety, and influences growth, energy, and bone metabolism. There has been great interest in the role of this hormone in chronic kidney disease-related protein energy wasting, thus, a positive leptin correlation with body mass index and fat mass was confirmed. This study was designed to determine the association of pre and post-kidney transplant leptin concentration with nutritional status and body composition. Materials and Methods: We studied 65 kidney transplant recipients. Nutritional status was evaluated before kidney transplantation and 6 months later using three different malnutrition screening tools (Subjective Global Assessment Scale (SGA), Malnutrition Inflammation Score (MIS), and Geriatric Nutritional Risk Index (GNRI)), anthropometric measurements, and body composition (bioelectrical impedance analysis (BIA)). Demographic profile, serum leptin levels, and other biochemical nutritional markers were collected. Statistical analysis was performed with R software. Results: Median age of the studied patients was 45 years, 42% were females, and 12% had diabetes. Leptin change was associated with body weight (p &lt, 0.001), waist circumference (p &lt, 0.001), fat mass (p &lt, 0.001) and body fat percentage (p &lt, 0.001), decrease in parathyroid hormone (PTH) (p &lt, 0.001) transferrin (p &lt, 0.001), diabetes mellitus (p = 0.010), and residual renal function (p = 0.039), but not dependent on dialysis vintage, estimated glomerular filtration rate (eGFR), or delayed graft function at any time during the study. After adjustment for age and sex, body mass index (BMI) (p &lt, 0.001), and body fat percentage (p &lt, 0.001) were independent variables significantly associated with post-transplant leptin change. Lower leptin values were found both before and after kidney transplantation in the SGA B group. GNRI as a nutritional status tool was strongly positively related to changes in leptin within the 6-month follow-up period. Conclusions: Kidney transplant recipients experience change in leptin concentration mainly due to an increase in fat mass and loss of muscle mass. GNRI score as compared to SGA or MIS score identifies patients in whom leptin concentration is increasing alongside an accumulation of fat and decreasing muscle mass. Leptin concentration evaluation in combination with BIA, handgrip strength measurement, and GNRI assessment are tools of importance in defining nutrition status in the early post-kidney transplant period.

Extracellular heat shock proteins (HSPs) mediate immunological functions and are involved in pathologies such as infection, stress, and cancer. Here, we demonstrated the dependence of an amount of HSP70 and HSP90 in serum vs. severity of acute pancreatitis (AP) on a cohort of 49 patients. Tethered bilayer lipid membranes (tBLMs) have been developed to investigate HSPs’ interactions with tBLMs that can be probed by electrochemical impedance spectroscopy (EIS). The results revealed that HSP70 and HSP90 interact via different mechanisms. HSP70 shows the damage of the membrane, while HSP90 increases the insulation properties of tBLM. These findings provide evidence that EIS offers a novel approach for the study of the changes in membrane integrity induced by HSPs proteins. Herein, we present an alternative electrochemical technique, without any immunoprobes, that allows for the monitoring of HSPs on nanoscaled tBLM arrangement in biologics samples such us human urine. This study demonstrates the great potential of tBLM to be used as a membrane based biosensor for novel, simple, and non-invasive label-free analytical system for the prediction of AP severity.

Background and Objectives: Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune, multi-factorial disease, in which environmental and genetic factors play a major role. RA is possibly linked to vitamin D deficiency and vitamin D receptor (VDR) gene polymorphisms, and research demonstrates that FokI variant susceptibility is associated with increased disease risk among Caucasians. The aim of this study was to evaluate vitamin D deficiency prevalence and its correlation to RA clinical parameters, and to determine the possible association of VDR gene polymorphisms and RA susceptibility in the Lithuanian population. Materials and Methods: Overall, 206 RA patients and 180 age- and sex-matched healthy controls were enrolled at Vilnius University Hospital Santaros Klinikos after informed consent was obtained. The disease activity score 28 C-reactive protein (DAS28 CRP), rheumatoid arthritis impact of disease (RAID) score, and health assessment questionnaire (HAQ) were recorded in RA patients, and 25(OH)D serum levels were evaluated by chemiluminescent microparticle immunoassay for all subjects. Four VDR gene polymorphisms, BsmI, FokI, ApaI, and TaqI, were assessed using real-time PCR instruments and genotyping assays in both groups. Results: The study registered a high prevalence of 25(OH)D deficiency (&lt, 50 nmol/L) in RA patients (61.55% (n = 127)). The mean serum concentration in RA patients (44.96 ± 21.92 (nmol/L)) was significantly lower than in the healthy controls (54.90 ± 22.82 (nmol/L)), p &lt, 0.0001. A significant inverse correlation between vitamin D level, DAS28 CRP, and HAQ scores was confirmed in RA patients, with p &lt, 0.05. Still, there was no significant association between the overall risk of RA disease for any allele or genotype of the four VDR loci tested. Conclusions: The study confirmed that vitamin D deficiency is prevalent among RA patients and the 25(OH)D level is significantly lower compared with healthy controls. Lower vitamin D concentration was related with increased disease activity and disability scores. However, genetic analysis of four VDR polymorphisms did not confer the susceptibility to RA in Lithuanian population.

This paper evaluates the prevalence and severity of periodontitis (PD) in patients with rheumatoid arthritis (RA), focusing on the link between the severity of PD with RA disease activity/disability scores, the influence of RA treatment on PD, and levels of vitamin D.A total of 93 RA patients were enrolled in the cross-sectional study and analyzed accordingly as RA-PD (N = 63, 67.8%) and RA-only (N = 30, 32.2%) groups. A number of associations between rheumatological clinical data, i.e., Disease Activity Score (DAS28 CRP), health assessment questionnaires, and PD severity (measured by periodontal outcome parameters) with regard to serum levels of vitamin D were assessed. The outcome variables were compared by parametric and non-parametric tests.A total of 29% of RA patients were diagnosed with severe PD. The RA-PD group presented a higher mean DAS28 CRP score in moderate-severe PD compared to periodontally healthy-initial stage PD subjects (4.49 ± 1.22 vs. 3.86 ± 1.58, p = 0.033). RA patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs) were less likely to be diagnosed with PD (p = 0.022) and revealed significantly lower PD outcome parameters, i.e., bleeding on probing (%) and bone loss (%) (p0.05). Vitamin D concentration was significantly lower in RA-PD group with diagnosed advanced severe PD (IV stage) compared to moderate PD (II stage) (39.61 ± 17.12 vs. 52.07 ± 18.23 nmol/l, p = 0.031).The study revealed a high prevalence of severe PD in RA patients, being significantly associated with higher RA disease activity and lower vitamin D level in RA-PD group, while bDMARD treatment was related to lower PD outcome parameters. Key Points • Severe PD is prevalent amongst RA patients and is associated with RA disease activity. The higher RA DAS28 CRP score is associated with moderate-severe PD compared to periodontally healthy-initial stage PD in RA patients. • Biologic DMARDs treatment used for RA is linked to lower PD rates and PD outcome parameters. • Significantly lower vitamin D level is found in advanced severe PD compared to moderate PD stage in RA-PD subjects.

Although laboratory medicine practise varies across the European Union’s (EU) member states, the extent of overlap in scope is such that a common syllabus describing the education and training associated with high-quality, specialist practise can be identified. In turn, such a syllabus can help define the common set of skills, knowledge and competence in a Common Training Framework (CTF) for non-medical Specialists in Laboratory Medicine under EU Directive 2013/55/EU (The recognition of Professional Qualifications). In meeting the requirements of the directive’s CTF patient safety is particularly enhanced when specialists seek to capitalise on opportunities for free professional migration across EU borders. In updating the fourth syllabus, the fifth expands on individual discipline requirements, new analytical techniques and use of statistics. An outline structure for a training programme is proposed together with expected responsibilities of trainees and trainers; reference is provided to a trainee’s log book. In updating the syllabus, it continues to support national programmes and the aims of EU Directive 2013/55/EU in providing safeguards to professional mobility across European borders at a time when the demand for highly qualified professionals is increasing in the face of a disparity in their distribution across Europe. In support of achieving a CTF, the syllabus represents EFLM’s position statement for the education and training that underpins the framework.

Purpose The objective of the study was to determine the differences in the numbers of endothelial microvesicles (EMV) after myocardial infarction (MI) and their association with oxidative stress. Materials and methods We included 15 post MI patients and 28 healthy controls. Samples were analysed by flow cytometry. We examined four EMV populations: 1) CD144+, CD42a-, CD61−, 2) CD144+, CD42a+, CD61−, 3) CD105+, CD42a-, CD61−and 4) CD31+, CD42a-, CD61−and determined a percentage of CD62e + EMV. Malondialdehyde concentration was determined by ultra-high performance liquid chromatography. Results The median of EMV counts differed between controls and patients in: CD105+ (10.91 microvesicles/μl vs. 33.68 microvesicles/μl, P = 0.006), CD144+, CD42a+ (312.87 microvesicles/μl vs. 73.29 microvesicles/μl, P The median of percentage of CD62e expression differed between controls and patients in: CD105+ (1.35% vs. 14.8%, P In patients, EMV counts correlated with low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) concentrations: CD105+: R = −0.69, P = 0.004 (LDL-C), R = −0.64, P = 0.01 (TC); CD144+, CD42a-: R = −0.68, P = 0.005 (LDL-C), R = −0.63, P = 0.011 (TC); CD144+: R = −0.54, P = 0.038 (HDL-C) and CD144+, CD42a-, CD62e+: R = 0.78, P = 0.001 (HDL-C). In controls, HDL-C concentration correlated with CD105+ (R = −0.395, P = 0.038) and CD105+, CD62e+ (R = −0.716, P Conclusions Changes in EMV levels after the MI period were observed. Counts of EMV and their CD62e expression correlated with dyslipidaemia and oxidative stress.

Background:Vitamin D is known for its immunomodulatory and epigenome interacting effects. Vitamin D deficiency is frequently observed in rheumatoid arthritis (RA) patients compared to healthy controls, is also named as a potential risk factor in RA ethiopatogenesis and may alter DNA methylation of certain genes [1,2]. Still, causality of vitamin D deficiency in RA patients needs to be elucidated.Objectives:The aim of the study was to evaluate relationship between DNA methylation status of vitamin D related genes (VDR,CYP24A1,CYP2R1), miRNA-155 expression, vitamin D level and its association with RA.Methods:CpG islands in promoter region of theVDR,CYP24A1,CYP2R1genes were chosen for DNA methylation analysis by means of pyrosequencing. DNA from blood mononuclear cells of 31 RA patients and 31 age and sex matched healthy controls was assessed for methylation pattern after informed consent was obtained in Vilnius university Hospital Santaros klinikos Centre of Rheumatology. For miRNA analysis quantitative reverse transcription PCR was used. Chemiluminescent microplate immunoassay was used to asses 25(OH)D serum levels.Results:25(OH)D concentrations varied from deficiency (CYP24A1methylation level was significantly higher in comparison toVDR(pCYP2R1(pCYP24A1hypermethylation was also observed in older subjects (p=0.012). The study demonstrated a significant positive correlation between vitamin D concentration andVDR,CYP2R1genes methylation intensity (r2=0.31, p=0.014; r2=0.25, p=0.042, respectively). However, gene methylation frequency and methylation intensity showed no significant difference between RA patients and healthy controls (VDR– 2.4vs2.6 %,CYP24A1– 16.6vs15.3 %,CYP2R1– 2.6vs2.6 %) (p>0.05). To note, miRNA-155 expression negatively correlated withCYP24A1methylation intensity (r2=-0.43, p=0.009).Conclusion:Our study identified significant associations between theVDRandCYP2R1promoter methylation and vitamin D concentration. However, no significant differences in DNA methylation pattern between RA patients and healthy controls were detected. MiR-155 expression was associated withCYP24A1methylation level, confirming its possible involvement in vitamin D metabolism. The data of our study suggests that epigenetic phenomena are significantly involved in vitamin D metabolism and may have an indirect effect on RA ethiopatogenesis.References:[1]Jeffery LE, et al. Nat Rev Rheumatol. 2016,12.4:201.[2]Fetahu IS et al. Front Physiol. 2014,5:164.Acknowledgments:This project has received funding from the Research Council of Lithuania (LMTLT), agreement No. S-MIP-17-12.Disclosure of Interests:None declared

Background Nowadays over-the-counter (OTC) drugs and dietary supplements are widely used. Their use can have a significant impact on the validity of laboratory results. The aim of this multicenter European study was to determine the frequency of consumption of various dietary products and OTC drugs among patients and explore their level of knowledge and awareness about the potential impact of various products on laboratory test results. Methods Eighteen European countries participated in this study. The survey was carried out anonymously on a subsequent series of outpatients (n=200) in each participating country. Included were patients who were referred to the laboratory for blood sampling and who voluntarily agreed to participate in the study. The survey included questions about the frequency of consumption of various products, awareness of the importance of informing physicians and laboratory staff about it and information about influence of preanalytical factors in general on laboratory test results. Results In total, 68% of patients were regularly taking at least one OTC drug or dietary supplement. The frequency of patients consuming at least one OTC drug or dietary supplement differed between countries (p=0.001). Vitamins (38%), minerals (34%), cranberry juice (20%), acetylsalicylic acid (ASA) (17%) and omega fatty acids (17%) were the most commonly used in our study. Conclusions The use of various OTC drugs and dietary supplements is highly prevalent in Europe and patients are often not willing to disclose this information to the laboratory staff and ordering physician. The education of both patients and healthcare staff is needed.

This study describes the development of a beverage made from curd whey with the addition of functional ingredients such as calcium, vitamin D3, prebiotic dietary fiber, and its influence on human health. Samples of beverages with added calcium phosphate or calcium lactate were analyzed for the selection of optimal calcium preparation. Quality attributes of beverages were evaluated in their fresh state and during storage at intervals of 15, 30, and 45 days. The beverage with calcium lactate was chosen as the one with most stable quality indices for evaluation of the effect on health status of volunteers (n=30). Five hundred milliliters of beverage were consumed daily by the volunteers over a period of 21 days. A significant decrease in low density lipoprotein (LDL)-cholesterol (P

Introduction : There are insufficient data regarding the changes in adipokine levels after laparoscopic adjustable gastric banding (LAGB) in diabetic and non-diabetic patients and their effects on insulin resistance and type 2 diabetes remission. Aim : To assess leptin, adiponectin, and insulin resistance changes after LAGB in diabetic and non-diabetic morbidly obese patients. Material and methods : One hundred and three patients (37 with and 66 without type 2 diabetes) underwent LAGB from January 2009 to January 2010. Glycated hemoglobin, insulin, adipokine levels and insulin resistance were evaluated preoperatively, and 1 and 4 years after LAGB. Results : The mean patient age was 45.9 ±11.7 years and mean preoperative body mass index was 47.5 ±7.3 kg/m2. A total of 80 of 103 patients (77.6%) completed the 4-year follow-up. After 4 years the mean excess weight loss was 38.8% and 39.5% in diabetic and non-diabetic patients respectively. Leptin levels decreased significantly in both groups at 1 year, but after 4 years this was noted only in non-diabetic patients. After 1 year adiponectin levels increased significantly only in non-diabetic patients (p = 0.003) and remained almost the same at 4 years. A significant decrease in insulin resistance was noted in both groups 1 year after LAGB and diabetes remission was observed in 23 (62.1%) patients. There was a negative correlation between preoperative insulin resistance and adiponectin levels throughout the follow-up period. Leptin levels positively correlated with BMI throughout the study period (baseline r = 0.45; p < 0.001; after 1 year r = 0.71; p < 0.001; after 4 years r = 0.68; p < 0.001). There was no significant correlation between leptin and adiponectin concentrations preoperatively or after 1 year; however, at 4 years it was significant (r = 0.27; p < 0.02). Conclusions : The most significant metabolic changes occurred within 1 year after LAGB. The 4-year follow-up revealed stabilization in metabolic indices rather than significant improvement.

Background: Inflammatory dilated cardiomyopathy (iDCM) is a common debilitating disease with poor prognosis that often leads to heart failure and may require heart transplantation. The aim of this study was to evaluate sera and biopsy samples from chronic iDCM patients, and to investigate molecular mechanism associated with left ventricular remodeling and disease progression in order to improve therapeutic intervention. Methods: Patients were divided into inflammatory and non-inflammatory DCM groups according to the immunohistochemical expression of inflammatory infiltrates markers: T-lymphocytes (CD3), active-memory T lymphocyte (CD45Ro) and macrophages (CD68). The inflammation, apoptosis, necrosis and fibrosis were investigated by ELISA, chemiluminescent, immunohistochemical and histological assays. Results: The pro-inflammatory cytokine IL-6 was significantly elevated in iDCM sera (3.3 vs. 10.98 μg/ml; P

Laboratory medicine’s practitioners across the European community include medical, scientific and pharmacy trained specialists whose contributions to health and healthcare is in the application of diagnostic tests for screening and early detection of disease, differential diagnosis, monitoring, management and treatment of patients, and their prognostic assessment. In submitting a revised common syllabus for post-graduate education and training across the 27 member states an expectation is set for harmonised, high quality, safe practice. In this regard an extended ‘Core knowledge, skills and competencies’ division embracing all laboratory medicine disciplines is described. For the first time the syllabus identifies the competencies required to meet clinical leadership demands for defining, directing and assuring the efficiency and effectiveness of laboratory services as well as expectations in translating knowledge and skills into ability to practice. In a ‘Specialist knowledge’ division, the expectations from the individual disciplines of Clinical Chemistry/Immunology, Haematology/Blood Transfusion, Microbiology/ Virology, Genetics and In Vitro Fertilisation are described. Beyond providing a common platform of knowledge, skills and competency, the syllabus supports the aims of the European Commission in providing safeguards to increasing professional mobility across European borders at a time when demand for highly qualified professionals is increasing and the labour force is declining. It continues to act as a guide for the formulation of national programmes supplemented by the needs of individual country priorities., peer-reviewed

Changes in lipid metabolism is one of the most important features of steroid sensitive nephrotic syndrome. Increased serum lipid level not always is connected with disease activity and sometimes may persist for long time, especially in frequently relapsing nephrotic syndrome. Hyperlipidemia and dyslipidemia are connected with cardiovascular diseases and development of glomerulosclerosis. Omega-3 (omega-3) polyunsaturated fatty acids have positive influence on lipid metabolism, diminishing hypercoagulation and a risk of cardiovascular diseases. The aim of this study was to examine influence of omega-3 polyunsaturated fatty acids on lipid disturbances in children with steroid sensitive nephrotic syndrome. Forty-eight patients were included in the study; 24 of them were treated with prednisolone (control group) and 24 were treated with prednisolone and fish oil (6 mg/day) along with symptomatic therapies. Serum lipid profile and spectrum of fatty acids before treatment and three months after start of the treatment were evaluated. Before treatment, contents of serum fatty acids and lipids did not differ between the groups. The study showed decrease in serum triglycerides (p0.06) and omega-6 polyunsaturated fatty acids (p0.02), increase in concentration of omega-3 polyunsaturated fatty acids and the ratio of 20:5 omega-3/20: omega-6 (eicosapentaenoic/arachidonic acids) (p0.001). Cholesterol, HDL-Ch, LDL-Ch concentrations did not change under the treatment with fish oil. We conclude that fish oil might be useful as an agent normalising lipid metabolism in children with steroid sensitive nephrotic syndrome.

Daiva Bironaite*, Dainius Daunoravicius, Julius Bogomolovas, Arturas Jakubauskas, Dalius Vitkus, Edvardas Zurauskas, Ieva Zasytyte, Kestutis Rucinskas, Algirdas Venalis, Virginija Grabauskiene Department of Stem Cell Biology, State Research Institute, Center for Innovative Medicine, Department of Pathology, Forensic Medicine and Pharmacology, Vilnius University, Faculty of Medicine, Vilnius, Lithuania, Department of Integrative Pathophysiology, Universitatsmedizin Mannheim, Mannheim, Germany, Center of Immunogenetics, Hematology, Oncology and Transfusion Medicine, Vilnius University, Department of Physiology, Biochemistry and Laboratory medicine, Clinic of Cardiovascular Diseases, Vilnius University, Faculty of Medicine, State Research Institute, Center for Innovative Medicine, Vilnius, Lithuania

Daiva Bironaite*, Dainius Daunoravicius, Julius Bogomolovas, Arturas Jakubauskas, Dalius Vitkus, Edvardas Zurauskas, Ieva Zasytyte, Kestutis Rucinskas, Algirdas Venalis, Virginija Grabauskiene Department of Stem Cell Biology, State Research Institute, Center for Innovative Medicine, Department of Pathology, Forensic Medicine and Pharmacology, Vilnius University, Faculty of Medicine, Vilnius, Lithuania, Department of Integrative Pathophysiology, Universitatsmedizin Mannheim, Mannheim, Germany, Center of Immunogenetics, Hematology, Oncology and Transfusion Medicine, Vilnius University, Department of Physiology, Biochemistry and Laboratory medicine, Clinic of Cardiovascular Diseases, Vilnius University, Faculty of Medicine, State Research Institute, Center for Innovative Medicine, Vilnius, Lithuania

AIM: To analyze the prognostic value of adipokines in predicting the course, complications and fatal outcome of acute pancreatitis (AP). METHODS: We performed the search of PubMed database and the systemic analysis of the literature for both experimental and human studies on prognostic value of adipokines in AP for period 2002-2012. Only the papers that described the use of adipokines for prediction of severity and/or complications of AP were selected for further analysis. Each article had to contain information about the levels of measured adipokines, diagnosis and verification of AP, to specify presence of pancreatic necrosis, organ dysfunction and/or mortality rates. From the very beginning, study was carried out adhering to the PRISMA checklist and flowchart for systemic reviews. To assess quality of all included human studies, the Quality Assessment of Diagnostic Accuracy Studies tool was used. Because of the high heterogeneity between the studies, it was decided to refrain from the statistical processing or meta-analysis of the available data. RESULTS: Nine human and three experimental studies were included into review. In experimental studies significant differences between leptin concentrations at 24 and 48 h in control, acute edematous and acute necrotizing pancreatitis groups were found (P = 0.027 and P < 0.001). In human studies significant differences between leptin and resitin concentrations in control and acute pancreatitis groups were found. 1-3 d serum adiponectin threshold of 4.5 μg/mL correctly classified the severity of 81% of patients with AP. This threshold yielded a sensitivity of 70%, specificity 85%, positive predictive value 64%, negative predictive value88% (area under curve 0.75). Resistin and visfatin concentrations differ significantly between mild and severe acute pancreatitis groups, they correlate with severity of disease, need for interventions and outcome. Both adipokines are good markers for parapancreatic necrosis and the cut-off values of 11.9 ng/mL and 1.8 ng/mL respectively predict the high ranges of radiological scores. However, the review revealed that all nine human studies with adipokines are very different in terms of methodology and objectives, so it is difficult to generalize their results. It seems that concentrations of the leptin and resistin increases significantly in patients with acute pancreatitis compared with controls. Serum levels of adiponectin, visfatin and especially resitin (positive correlation with Acute Physiology and Chronic Health Evaluation II, Ranson and C-reactive protein) are significantly different in mild acute pancreatitis and severe acute pancreatitis patients, so, they can serve as a markers for the disease severity prediction. Resistin and visfatin can also be used for pancreatic and parapancreatic necrosis prediction, interventions needs and possible, outcome. CONCLUSION: High levels of adipokines could allow for prediction of a severe disease course and outcome even in small pancreatic lesions on computed tomography scans.

Liutkevicius A., Speicienė V., Alencikienė G., Mieželienė A., Narkevicius R., Kaminskas A., Abaravicius J.A., Vitkus D., Jablonskienė V., Sekmokienė D. (2016): Fermented buttermilk-based beverage: impact on young volunteers’ health parameters. Czech J. Food Sci., 34: 143–148. The technology of a functional fermented buttermilk-based beverage was developed and the impact of beverage con sumption on the health parameters of young volunteers was studied. Three functional beverages were made on the basis of buttermilk, which differed in the composition. The beverage containing the buttermilk-skimmed milk-milk protein concentrate (0.3%) as a product with the preferred quality characteristics (synaeresis, viscosity, sensory properties, and acceptability) was used for further studies regarding the impact on human health. The medical nutrition experi ments did not show any statistically significant effect on the biochemical blood parameters of 25 young volunteers after a 21-day period of the consumption of fermented buttermilk beverage with milk protein concentrate, although some of them (e.g. total, low- and high-density cholesterol, triacylglycerol concentrations, etc.) slightly decreased. The anthropometric and body composition, arterial blood pressure, and pulse evaluation indicators of recipients did not change significantly.