A vision to the future: value-based laboratory medicine.

The ultimate goal of value-based laboratory medicine is maximizing the effectiveness of laboratory tests in improving patient outcomes, optimizing resources and minimizing unnecessary costs. This approach abandons the oversimplified notion of test volume and cost, in favor of emphasizing the clinical utility and quality of diagnostic tests in the clinical decision-making. Several key elements characterize value-based laboratory medicine, which can be summarized in some basic concepts, such as organization of in vitro diagnostics (including appropriateness, integrated diagnostics, networking, remote patient monitoring, disruptive innovations), translation of laboratory data into clinical information and measurable outcomes, sustainability, reimbursement, ethics (e.g., patient empowerment and safety, data protection, analysis of big data, scientific publishing). Education and training are also crucial, along with considerations for the future of the profession, which will be largely influenced by advances in automation, information technology, artificial intelligence, and regulations concerning in vitro diagnostics. This collective opinion paper, composed of summaries from presentations given at the two-day European Federation of Laboratory Medicine (EFLM) Strategic Conference "A vision to the future: value-based laboratory medicine" (Padova, Italy; September 23-24, 2024), aims to provide a comprehensive overview of value-based laboratory medicine, projecting the profession into a more clinically effective and sustainable future.

EFLM Task Force Preparation of Labs for Emergencies (TF-PLE) recommendations for reinforcing cyber-security and managing cyber-attacks in medical laboratories.

The healthcare systems are a prime target for cyber-attacks due to the sensitive nature of the information combined with the essential need for continuity of care. Medical laboratories are particularly vulnerable to cyber-attacks for a number of reasons, including the high level of information technology (IT), computerization and digitization. Based on reliable and widespread evidence that medical laboratories may be inadequately prepared for cyber-terrorism, a panel of experts of the Task Force Preparation of Labs for Emergencies (TF-PLE) of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) has recognized the need to provide some general guidance that could help medical laboratories to be less vulnerable and better prepared for the dramatic circumstance of a disruptive cyber-attack, issuing a number of consensus recommendations, which are summarized and described in this opinion paper.

The Effects of Pregestational Overweight and Obesity on Maternal Lipidome in Pregnancy: Implications for Newborns' Characteristics.

Obesity is an important risk factor for the development of pregnancy complications. We investigated the effects of pregestational overweight and obesity on maternal lipidome during pregnancy and on newborns' characteristics. The study encompassed 131 pregnant women, 99 with pre-pregnancy body mass index (BMI) < 25 kg/m2 and 32 with BMI ≥ 25 kg/m2. Maternal lipid status parameters, plasma markers of cholesterol synthesis and absorption and sphingolipids were determined in each trimester. Data on neonatal height, weight and APGAR scores were assessed. The results showed a higher prevalence (p < 0.05) of pregnancy and childbirth complications among the participants with elevated pregestational BMI. Levels of total cholesterol, HDL-cholesterol (p < 0.05) and LDL-cholesterol (p < 0.01) were significantly lower, and concentrations of triglycerides were higher (p < 0.05) in women with increased pre-gestational BMI. Lower concentrations of the cholesterol synthesis marker, desmosterol, in the 2nd trimester (p < 0.01) and the cholesterol absorption marker, campesterol, in each trimester (p < 0.01, p < 0.05, p < 0.01, respectively) were also found in this group. Markers of maternal cholesterol synthesis were in positive correlation with neonatal APGAR scores in the group of mothers with healthy pre-pregnancy weight but in negative correlation in the overweight/obese group. Our results indicate that gestational adaptations of maternal lipidome depend on her pregestational nutritional status and that such changes may affect neonatal outcomes.

Digital transformation towards the clinical laboratory of the future. Perspectives for the next decade.

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.

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.

Quality benchmarking of smartphone laboratory medicine applications: comparison of laboratory medicine specialists' and non-laboratory medicine professionals' evaluation.

OBJECTIVES: There are many mobile health applications (apps) now available and some that use in some way laboratory medicine data. Among them, patient-oriented are of the lowest content quality. The aim of this study was to compare the opinions of non-laboratory medicine professionals (NLMP) with those of laboratory medicine specialists (LMS) and define the benchmarks for quality assessment of laboratory medicine apps. METHODS: Twenty-five volunteers from six European countries evaluated 16 selected patient-oriented apps. Participants were 20-60 years old, 44% were females, with different educational degrees, and no professional involvement in laboratory medicine. Each participant completed a questionnaire based on the Mobile Application Rating Scale (MARS) and the System Usability Scale, as previously used for rating the app quality by LMS. The responses from the two groups were compared using the Mann-Whitney U test and Spearman correlation. RESULTS: The median total score of NLMP app evaluation was 2.73 out of 5 (IQR 0.95) compared to 3.78 (IQR 1.05) by the LMS. All scores were statistically significantly lower in the NLMP group (p<0.05), except for the item Information quality (p=0.1631). The suggested benchmarks for a useful appear: increasing awareness of the importance and delivering an understanding of persons' own laboratory test results; understandable terminology; easy to use; appropriate graphic design, and trustworthy information. CONCLUSIONS: NLMP' evaluation confirmed the low utility of currently available laboratory medicine apps. A reliable app should contain trustworthy and understandable information. The appearance of an app should be fit for purpose and easy to use.

Quality evaluation of smartphone applications for laboratory medicine.

Background Many of the mobile applications (apps) used for delivering health interventions involve laboratory medicine data. This survey was conducted to search the online market for health apps that manage laboratory medicine data. The aim was to review them and perform a quality evaluation. Methods Apps search criteria were "Lab results blood work", "Lab results", and "Health apps". After the stepwise exclusion process, 52 selected apps were downloaded and analyzed. For review and content analysis of the apps, a multidimensional tool for classifying and rating the quality of mobile health apps - Mobile App Rating Scale (MARS), was used. Results Selected apps were classified into five categories according to their intended use by patients or physicians, and the type of data engaged. Spearman's correlation analysis found significant correlations between MARS individual scoring items, as with the subjective quality and number of technical aspects. Kruskal-Wallis analysis showed a significant difference in the number of technical aspects employed, MARS engagement and informational quality score items, total score, and subjective quality. The lowest values for all of these items were in the category of apps designed for patients, and the post hoc test showed that the difference was statistically significant between this and the values in all other categories. Conclusions Apps designed for patients, are of the poorest quality, considering the total quality of the content and information they provide, estimated using the MARS tool. This estimation needs to be validated for laboratory medicine apps, and eventually modified after consideration of specific quality benchmarks.

Evaluation of the renal function using serum Cystatin C following open and endovascular aortic aneurysm repair.

Objectives Controversies regarding renal function impairment after open and endovascular aortic aneurysm repair still exist. The purpose of this study was to evaluate the renal function following open repair and endovascular aneurysm repair using Cystatin C. Methods This prospective, observational case-control study was conducted in tertiary referral centre over 3 years, starting from 2012. In total, 60 patients operated due to infrarenal AAA either by means of open repair (30 patients) or endovascular aneurysm repair (30 patients) were included in the study. Biochemical markers of renal function (sCr, urea, potassium) were recorded pre-operatively and at these specific time points, immediately after the operation and at discharge, home (third postoperative day, endovascular aneurysm repair group) or from intensive care unit (third postoperative day, open repair group). Multivariate and propensity score adjustments were used to control for the baseline differences between the groups. Results Creatinine levels in serum remained unchanged during the hospital stay in both groups without significant differences at any time point. Cystatin C levels in endovascular aneurysm repair patients significantly increased postoperatively and restored to values comparable to baseline at the discharge (0.865 ± 0.319 vs. *0.962 ± 0.353 vs. 0.921 ± 0.322, * p < 0.001). Cystatin C levels in patients treated with the open surgery was decreasing over time but not statistically significant comparing to Cystatin C values at the admission. However, decrease in Cystatin C serum levels in patients treated with conventional surgery resulted in statistically significant lower values compared to endovascular aneurysm repair patients both postoperatively and at the time of discharge (0.760 ± 0.225 vs. 0.962 ± 0.353, p < 0.05; 0.750 vs. 0.156, p < 0.05). Both multivariate linear regression models and propensity score adjustment confirm that, even after correction for previously observed intergroup differences, type of surgery, i.e. endovascular aneurysm repair is independently associated with the higher levels of Cystatin C both postoperatively and at the discharge. Conclusions Dynamics of Cystatin C levels have been proven as a more vulnerable marker of renal dysfunction. Endovascular aneurysm repair is associated with higher levels of kidney injury markers.

A survey of patients' views from eight European countries of interpretive support from Specialists in Laboratory Medicine.

BACKGROUND: There is increasing interest in direct patient engagement including receiving their laboratory medicine results. We previously established an appetite for Specialists in Laboratory Medicine to support patients in understanding results. The aim of this study was to establish whether patients agreed with such an approach, determined through surveying views in eight European countries. METHODS: A standardized five-question survey was administered across eight European countries to a total of 1084 individuals attending medical outpatient clinics, with 100 patients each in Poland, Serbia, Netherlands, Turkey and Czech Republic, 101 in Estonia, 116 in Denmark and 367 in Norway. The responses across countries were compared using the chi-square test (p<0.05). RESULTS: Patients wanting their results ranged from 50% to 94% (mean 65%) of those responding positively, a mean of 72% wanted additional information with their results; direct receipt was preferred over referral to a website. Specialists in Laboratory Medicine providing such information were acceptable to a mean of 62% of those respondents wishing their results; in countries where payment was possible, there was little interest in making additional payment for such a service. CONCLUSIONS: A clear proportion of patients are interested in receiving their laboratory medicine results, the majority with explanatory notes; a role for Specialists in Laboratory Medicine is acceptable and raises the potential for direct engagement by such specialists with patients offering a new paradigm for the provision of laboratory medicine activities.

The Role of Oxidative Stress in the Clinical Manifestations of Childhood Asthma.

INTRODUCTION: The significance of oxidative stress in pathogenesis of childhood asthma was recognized, but its role in the clinical manifestations of disease is still unclear. MATERIALS AND METHODS: The study was conducted in 96 asthmatic children. The urinary biomarker of oxidative stress, 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxodG/creatinine) was determined by using HPLC-MS/MS. ELISA was performed to measure myeloperoxidase (MPO) and Cu,Zn- superoxide dismutase (Cu,Zn-SOD) in serum. RESULTS: Logistic regression analysis revealed that female gender, tobacco smoke exposure, and increased 8-oxodG/creatinine were associated with risk for intermittent asthma, while the positive allergy test and increased Cu,Zn-SOD were associated with eczema in asthmatic children. Higher MPO (p = 0.033), and percent of granulocytes (p = 0.030) were found in severe persistent asthma in comparison to intermittent or mild persistent asthma. CONCLUSION: The main findings that TSE-induced oxidative stress is a risk for intermittent asthma and eczema may be clinically significant for the disease prevention and therapeutic improvements.

European views on patients directly obtaining their laboratory test results.

BACKGROUND: Medicine is a highly professionalized endeavour, by tradition centred on the authority of physicians. Better education and the advent of the information age cater for increased demands on society in general and on health care in particular to enable people to make informed decisions regarding themselves. Participation in medical decisions requires informed knowledge which is hard to obtain without substantial and time consuming professional help. METHODS: We performed a survey amongst the member organizations of European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) in order to investigate the recognition and preparedness of providing help to patients in interpreting their laboratory results. RESULTS: Out of 40 EFLM Member Societies, 27 sent their responses to the survey. In most cases the first line delivery of laboratory results to physicians is by computer link (63%). Patients receive their laboratory results on demand from their physician in 60% of cases. However, 34% of laboratory specialists showed a negative attitude for delivering laboratory results to patients. Yet, in 48% of countries 1-5 patients per day ask a laboratory specialist about the significance of laboratory results outside the reference range. When patients are informed about the purpose of laboratory testing, they seek information primarily from their physician, followed by the internet and the Specialist in Laboratory Medicine. CONCLUSIONS: Changing practices increasingly enabling patient access to their records are on the increase facilitated by recent innovations in information technologies. Successful transfer of some of the responsibilities of physicians, demands a mutual triangular dialogue between the patient, their physician and laboratory medicine.

Structural myocardial alterations in diabetes and hypertension: the role of galectin-3.

BACKGROUND: Galectin-3 is a protein widely distributed in the heart, brain and blood vessels, and has a regulatory role in inflammation, immunology and cancer. Many studies demonstrated that the increased level of galectin-3 is associated with progressive fibrosis and stiffening of the myocardium. The aim of this study was to investigate the role of galectin-3 in patients with type 2 diabetes (T2D) and/or arterial hypertension (HT). METHODS: Study population included 189 patients, with no coronary artery disease, divided into three groups: group 1 (T2D), group 2 (T2D+HT), and group 3 (HT). All subjects underwent routine laboratory tests, as well as specific biomarkers assessment [galectin-3, glycosylated hemoglobin (HbA1c), N- terminal fragment B-type natriuretic peptide (NT-proBNP)]. Cardiological evaluation included physical examination, transthoracic tissue Doppler echocardiography and stress echocardiography. RESULTS: The results of this study demonstrated significantly increased levels of galectin-3, blood glucose, and HbA1c in group 2. Also, echocardiographicaly, left ventricular (LV) diameters and IVS thickness were increased in this group of patients. Furthermore, in the same cohort a positive correlation between galectin-3 and NT-pro BNP, and galectin-3 and LV mass were demonstrated. In addition, a negative correlation between galectin-3 and LV end-diastolic diameter was revealed. CONCLUSIONS: This study revealed that levels of galectin-3 were higher in patients with both T2D and HT, and correlated with LV mass, indicating the potential role of this biomarker for early detection of myocardial structural and functional alterations.

Indirect estimation of age-related reference limits of thyroid parameters: a cross-sectional study of outpatients' results.

OBJECTIVES: Defining adequate reference limits (RLs) for thyroid hormones is an important task for support monitoring and the treatment of subclinical thyroid disease. We determined whether there are age-related RLs for thyroid parameters in male and female outpatients free of overt thyroid disease. DESIGN: We analyzed 22,860 results (11,440 male and 11,420 female outpatients above the age of 18) for thyrotropin (TSH), free thyroxine (fT4) and total triiodothyronine (T3) that were stored in our laboratory information system between 2008 and 2011. We calculated the 2.5th and 97.5th centiles for the analyzed thyroid parameters. RESULTS: Our results indicate higher TSH levels with ageing, with a significant difference (p < 0.05) between the 97.5th centiles for males and females older than 70 (5.07 mIU/L and 4.10 mIU/L), but also a significant difference between male and female fT4 from 31 to 40 and from 41 to 50 years old (18.4 vs 14.9 pmol/L and 19.0 vs 15.9 pmol/L, p < 0.05), respectively. Overall indirect estimates of the 97.5th centiles for TSH for males and females were not significantly different and were below the generally recommended upper limit (4.01 mIU/L and 4.20 mIU/L, respectively). In addition, we found no statistically significant change in mean T3 values in the analyzed population. CONCLUSIONS: This cross-sectional study indicates change in TSH and fT4 levels with ageing and gender-related upper limits. This suggests that by using indirect estimation a laboratory could provide clinicians with more accurate gender- and age-specific RLs for thyroid parameters.

Analysis of total RNA as a potential biomarker of developmental neurotoxicity in silico.

A vast number of neurodegenerative disorders arise from neurotoxicity. In neurotoxicity, more than 250 RNA molecules are up and downregulated. The manuscript investigates the exposure of chlorpyrifos organophosphate pesticide (COP) effect on total RNA in murine brain tissue in 4 genotypes for in silico neurodegeneration development. The GSE58103 dataset from the Gene Expression Omnibus (GEO) database applies for data preprocessing, normalization, and quality control. Differential expression analysis (DEG) uses the limma package in R. Study compared expression profiles from murine fetal brain tissues across four genotypes: PON-1 knockout (KO), tgHuPON1Q192 (Q-tg), tgHuPON1R192 (R-tg), and wild-type (WT). We analyze 60 samples, 15 samples per genotype, to identify DEGs. The significance criteria are adjusted p-value <.05 and a |log2 fold change| > 1. The study identifies microRNA485 as the potential biomarker of COP toxicity using the GSE58103 dataset. Significant differences exist for microRNA485 between KO and WT groups by differential expression analysis. Moreover, graphical analysis shows sample relationships among genotype groups. MicroRNA485 represents a promising biomarker for developmental COP neurotoxicity by utilizing in silico analysis in scientific practice.

Enzyme ChE, cholinergic therapy and molecular docking: Significant considerations and future perspectives.

Enzyme Che plays an essential role in cholinergic and non-cholinergic functions. It is present in the fertilized/unfertilized eggs and sperm of different species. Inclusion criteria for data collection from electronic databases NCBI and Google Scholar are enzyme AChE/BChE, cholinergic therapy, genomic organization and gene transcription, enzyme structure, biogenesis, transport, processing and localization, molecular signaling and biological function, polymorphism and influencing factors. Enzyme Che acts as a signaling receptor during hematopoiesis, protein adhesion, amyloid fiber formation, neurite outgrowth, bone development, and maturation, explaining the activity out of synaptic neurotransmission. Polymorphism in the Che genes correlates to various diseases and diverse drug responses. In particular, change accompanies cancer, neurodegenerative, and cardiovascular disease. Literature knowledge indicates the importance of Che inhibitors that influence biochemical and molecular pathways in disease treatment, genomic organization, gene transcription, structure, biogenesis, transport, processing, and localization of Che enzyme. Enzyme Che polymorphism changes indicate the possibility of efficient and new inhibitor drug target mechanisms in diverse research areas.

Uncovering novel therapeutic targets in glucose, nucleotides and lipids metabolism during cancer and neurological diseases.

BACKGROUND: Cell metabolism functions without a stop in normal and pathological cells. Different metabolic changes occur in the disease. Cell metabolism influences biochemical and metabolic processes, signaling pathways, and gene regulation. Knowledge regarding disease metabolism is limited. OBJECTIVE: The review examines the cell metabolism of glucose, nucleotides, and lipids during homeostatic and pathological conditions of neurotoxicity, neuroimmunological disease, Parkinson's disease, thymoma in myasthenia gravis, and colorectal cancer. METHODS: Data collection includes electronic databases, the National Center for Biotechnology Information, and Google Scholar, with several inclusion criteria: cell metabolism, glucose metabolism, nucleotide metabolism, and lipid metabolism in health and disease patients suffering from neurotoxicity, neuroinflammation, Parkinson's disease, thymoma in myasthenia gravis. The initial number of collected and analyzed papers is 250. The final analysis included 150 studies out of 94 selected papers. After the selection process, 62.67% remains useful. RESULTS AND CONCLUSION: A literature search shows that signaling molecules are involved in metabolic changes in cells. Differences between cancer and neuroimmunological diseases are present in the result section. Our finding enables insight into novel therapeutic targets and the development of scientific approaches for cancer and neurological disease onset, outcome, progression, and treatment, highlighting the importance of metabolic dysregulation. Current understanding, emerging research technologies and potential therapeutic interventions in metabolic programming is disucussed and highlighted.

Differences in HDL Remodeling during Healthy Pregnancy and Pregnancy with Cardiometabolic Complications.

This study investigated the longitudinal trajectory of changes in antioxidative and anti-inflammatory high-density lipoprotein (HDL) components during healthy pregnancy and pregnancy with cardiometabolic complications. We recruited and longitudinally followed 84 women with healthy pregnancies and 46 pregnant women who developed cardiometabolic pregnancy complications (gestational diabetes mellitus and hypertensive disorders of pregnancy). Their general lipid profiles, oxidative stress status, inflammatory status, and antioxidative and anti-inflammatory HDL components were analyzed. The results of our study confirmed the expected trajectory for the routine lipid parameters. Our study results indicate more intensive oxidative stress and a higher level of inflammation in the group with complications compared with the control group. Sphingosine-1-phosphate (S1P) was significantly lower in the first trimester in the group with complications compared with the control group (p < 0.05). We did not find significant differences in the apolipoprotein A1 (Apo A1) concentrations in the first trimester between the control group and the group with complications, but in the second and third trimesters, the group with complications had significantly higher concentrations (p < 0.001, p < 0.05, respectively). The S1P, paraoxonase 1 (PON1), and serum amyloid A (SAA) concentrations were significantly lower in the group with complications in the first trimester. During the second trimester, only the SAA concentrations were identified as significantly lower in the group with complications compared with the control group, while in the third trimester, the PON1, apolipoprotein M (Apo M), and SAA concentrations were all significantly lower in the group with complications. Through a multivariate binary logistic regression analysis, the S1P concentration in the first trimester was distinguished as an HDL-associated marker independently associated with cardiometabolic pregnancy complications. In conclusion, our study results showed that HDL remodeling differs between healthy pregnancies and pregnancies with maternal cardiometabolic complications, with changed HDL composition and functionality consequently impacting its biological functionality in the latter case.

Measurement uncertainty.

Over time, the metrological concept of uncertainty in measurement has been very successfully integrated into laboratory sciences. For proper implementation, an understanding of specific metrology terminology and additional concepts such as metrology traceability and commutability is necessary. Although the original thinking about measurement uncertainty in laboratory medicine suggests the complexity of the concept, it basically refers to the result as the end product of the entire laboratory process. Although the data on measurement uncertainty can be expressed quantitatively, the basis of this concept is the continuous evaluation of all phases of the laboratory process. This means that laboratory experts should keep in mind that the extra-analytical phases (on which the uncertainty of the measurement results may depend the most) must be continuously monitored. The analytical phase can be "held in check" by established internal and external quality control processes. It is the internal/external quality control data that is used to calculate the numerical value of the measurement uncertainty of the measurement results. Although over time the awareness of laboratory experts regarding the concept of measurement uncertainty has increased, there are still many challenges that need to be followed, and the last one is how to achieve a balance between understanding, evaluation process and application of measurement uncertainty data of measurement results for complete and ultimate practical use.