Diurnal and day-to-day biological variation of salivary cortisol and cortisone.

OBJECTIVES: There is a growing interest in the relevance of salivary cortisol and cortisone concentrations in stress-related research. To correctly attribute the magnitude of salivary cortisol and cortisone variation as an effect of a stressful event, a coherent understanding of the day-to-day intra-individual and inter-individual variability across the diurnal cycle of the two steroids is required. However, such information is currently lacking. METHODS: This study aimed to overcome these existing limitations by performing an investigation of the biological variation (BV) of salivary cortisol and cortisone within one day and between five days using an LC-MS/MS method. Saliva samples were collected from 20 healthy volunteers immediately after waking up, at 8:00, 12:00, 15:00, 19:00 and 23:00 on each day over five days. All samples were analyzed in duplicate in one run. Nested ANOVA was used to calculate the sums of squares for analytical and biological components of variation. RESULTS: The within-subject BV of salivary cortisol and cortisone (CVI) ranged from a minimum of 29.3 and 19.0 % to a maximum of 56.5 and 49.1 %, respectively, while the between-subject biological variation (CVG) ranged from 29.7 and 29.0 % to 51.6 and 43.6 %. The reference change values (RCVs) ranged from 96 to 245 % for cortisol and from 55 to 194 % for cortisone. A medium index of individuality was observed for both compounds at all time points. CONCLUSIONS: This study provides updated BV estimates and RCVs for different times of day that can be used to assess the magnitude of change in biomarkers in future stress-related research.

Recommendations for blood sampling in emergency departments from the European Society for Emergency Medicine (EUSEM), European Society for Emergency Nursing (EuSEN), and European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group for the Preanalytical Phase. Executive summary.

AIM: Blood Sampling Guidelines have been developed to target European emergency medicine-related professionals involved in the blood sampling process (e.g. physicians, nurses, phlebotomists working in the ED), as well as laboratory physicians and other related professionals. The guidelines population focus on adult patients. The development of these blood sampling guidelines for the ED setting is based on the collaboration of three European scientific societies that have a role to play in the preanalytical phase process: EuSEN, EFLM, and EUSEM. The elaboration of the questions was done using the PICO procedure, literature search and appraisal was based on the GRADE methodology. The final recommendations were reviewed by an international multidisciplinary external review group. RESULTS: The document includes the elaborated recommendations for the selected sixteen questions. Three in pre-sampling, eight regarding sampling, three post-sampling, and two focus on quality assurance. In general, the quality of the evidence is very low, and the strength of the recommendation in all the questions has been rated as weak. The working group in four questions elaborate the recommendations, based mainly on group experience, rating as good practice. CONCLUSIONS: The multidisciplinary working group was considered one of the major contributors to this guideline. The lack of quality information highlights the need for research in this area of the patient care process. The peculiarities of the emergency medical areas need specific considerations to minimise the possibility of errors in the preanalytical phase.

Analysis of thicknesses of blood collection needle by scanning electron microscopy reveals wide heterogeneity.

OBJECTIVES: The preanalytical phase in clinical laboratory diagnostics is currently receiving more and more attention. This term describes one part of actions and aspects of the "brain-to-brain cycle" of the medical laboratory diagnostic procedure that take place before the analytical phase. However, the preanalytical activities, the handling of unsuitable samples and the reporting procedures are neither fully standardized nor harmonized worldwide. The influence of the properties of the blood collection needle must be acknowledged. In this work, we focused on the investigation of the internal structure and size of standardized 21G blood collection needles. METHODS: All parameters were measured with a scanning electron microscope using a Jeol model JSM-6000PLUS. Our. RESULTS: The obtained data shows that the internal surfaces of the needles vary greatly from manufacturer to manufacturer (by around 35 %), and this may play an important role in influencing blood flow and even the risk of blood cell injury (especially hemolysis) during blood drawing. CONCLUSIONS: The differential actual needle diameters can vary greatly between needle manufactures and this variety may have a significant impact on laboratory values and may also lead to specimen rejection.

Being fit in the COVID-19 era and future epidemics prevention: Importance of cardiopulmonary exercise test in fitness evaluation.

Endurance and resistance physical activity have been shown to stimulate the production of immunoglobulins and boost the levels of anti-inflammatory cytokines, natural killer cells, and neutrophils in the bloodstream, thereby strengthening the ability of the innate immune system to protect against diseases and infections. Coronavirus disease 19 (COVID-19) greatly impacted people's cardiorespiratory fitness (CRF) and health worldwide. Cardiopulmonary exercise testing (CPET) remains valuable in assessing physical condition, predicting illness severity, and guiding interventions and treatments. In this narrative review, we summarize the connections and impact of COVID-19 on CRF levels and its implications on the disease's progression, prognosis, and mortality. We also emphasize the significant contribution of CPET in both clinical evaluations of recovering COVID-19 patients and scientific investigations focused on comprehending the enduring health consequences of SARS-CoV-2 infection.

Artificial intelligence in the pre-analytical phase: State-of-the art and future perspectives.

The use of artificial intelligence (AI) has become widespread in many areas of science and medicine, including laboratory medicine. Although it seems obvious that the analytical and post-analytical phases could be the most important fields of application in laboratory medicine, a kaleidoscope of new opportunities has emerged to extend the benefits of AI to many manual labor-intensive activities belonging to the pre-analytical phase, which are inherently characterized by enhanced vulnerability and higher risk of errors. These potential applications involve increasing the appropriateness of test prescription (with computerized physician order entry or demand management tools), improved specimen collection (using active patient recognition, automated specimen labeling, vein recognition and blood collection assistance, along with automated blood drawing), more efficient sample transportation (facilitated by the use of pneumatic transport systems or drones, and monitored with smart blood tubes or data loggers), systematic evaluation of sample quality (by measuring serum indices, fill volume or for detecting sample clotting), as well as error detection and analysis. Therefore, this opinion paper aims to discuss the state-of-the-art and some future possibilities of AI in the preanalytical phase.

Physical Activity, Long-COVID, and Inactivity: A Detrimental Endless Loop.

The risk of developing medium- and long-term sequelae after recovery from COVID-19 is validated. Long-COVID burden represents a major health care issue, thus paving the way to effective prevention and/or treatment measures. Physical activity prevents many human pathologies, including COVID-19. Being physically active before and immediately after a severe acute respiratory syndrome coronavirus 2 infection substantially lowers the risk of developing long-COVID. In addition, long-COVID is an important cause of physical inactivity. Physically inactive individuals are at increased risk of developing long-COVID, while patients with long-COVID are more likely to reduce their physical activity levels after recovering from the acute infection, with the risk of generating a continuous loop. This harmful interaction needs to be recognized by public health institutions, and the adoption of physical activity as a routine clinical practice in all individuals after a severe acute respiratory syndrome coronavirus 2 infection needs to be proactively promoted.

The impact of physiological variations on personalized reference intervals and decision limits: an in-depth analysis.

The interpretation of laboratory data is a comparative procedure. Physicians typically need reference values to compare patients' laboratory data for clinical decisions. Therefore, establishing reliable reference data is essential for accurate diagnosis and patient monitoring. Human metabolism is a dynamic process. Various types of systematic and random fluctuations in the concentration/activity of biomolecules are observed in response to internal and external factors. In the human body, several biomolecules are under the influence of physiological rhythms and are therefore subject to ultradian, circadian and infradian fluctuations. In addition, most biomolecules are also characterized by random biological variations, which are referred to as biological fluctuations between subjects and within subjects/individuals. In routine practice, reference intervals based on population data are used, which by nature are not designed to capture physiological rhythms and random biological variations. To ensure safe and appropriate interpretation of patient laboratory data, reference intervals should be personalized and estimated using individual data in accordance with systematic and random variations. In this opinion paper, we outline (i) the main variations that contribute to the generation of personalized reference intervals (prRIs), (ii) the theoretical background of prRIs and (iii) propose new methods on how to harmonize prRIs with the systematic and random variations observed in metabolic activity, based on individuals' demography.

Pearls and Pitfalls in the Measurement of Direct Oral Anticoagulants.

Due to their widespread use, testing for direct oral anticoagulants (DOACs) has become urgent in certain clinical situations. Screening based on widely available, rapid, and simple hemostasis assays such as prothrombin time, activated partial thromboplastin time, or even diluted Russel Viper venom time may provide sufficient evidence of "over-coagulation" and could be used "in small/peripheral/spoke laboratories" as an emergency strategy, but is not thought to be reliable for driving clinical decision making. Given their good correlation with plasma concentration, urine dipsticks may be considered a valuable alternative for emergency screening, although their performance is dependent on renal function, may vary depending on the time since the last urination, and there may be problems of interfacing with the laboratory/hospital information system. Separation methods based on liquid chromatography and mass spectrometry may be clinically questionable, since they measure the concentration rather than the actual inhibitory effect of DOACs, are relatively expensive, cumbersome and time consuming, and therefore seem unsuitable for most conditions requiring urgent clinical decision making. A proposed approach therefore involves establishing a network of routine clinical laboratories, designating a reference center where DOAC tests could be available 24/7, establishing a clear diagnostic care pathway for ordering the tests from the laboratory and standard operating procedures for performing them, the use of the diluted thrombin time for dabigatran and anti-FXa assays (drug-calibrated) for rivaroxaban, apixaban, and edoxaban, as well as providing expert advice throughout the testing process, from ordering to interpretation of results.

Red blood cell distribution width (RDW) reflects disease severity in patients with carbon monoxide poisoning: systematic literature review and meta-analysis.

No definitive prognostic biomarkers for carbon monoxide (CO) poisoning have been proposed. The aim of this study is to investigate, through a systematic literature review and pooled analysis, whether red blood cell distribution width (RDW) can predict disease severity in CO-poisoned patients. We performed an electronic search in Scopus and PubMed using the keywords: 'red blood cell distribution width' OR 'RDW' AND 'carbon monoxide' AND 'poisoning,' with no time or language restrictions (i.e. through August 2023) to find clinical studies that examined the value of RDW in patients with varying severity of CO poisoning. The analysis was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 reporting checklist. We identified 29 articles, seven of which were included in our analysis, with a total of 1979 CO-poisoned patients, 25.9% of whom were severely ill. In all but one of the studies, the RWD mean or median value was higher in CO-poisoned patients with severe disease. The weighted mean difference (WMD) of RDW was 0.36 (95% confidence interval (CI), 0.26-0.47)%. In the three articles in which the severity of illness in CO-poisoned patients was defined as cardiac injury, the WMD of the RDW was 1.26 (95%CI, 1.02-1.50)%. These results suggest that monitoring RDW in CO-poisoned patients may help to determine the severity of disease, particularly cardiac injury.

Unfractionated heparin: optimizing laboratory monitoring and reducing unwanted interference in everyday hemostasis test practice.

Unfractionated heparin (UFH) serves as a commonly used anticoagulant. It is widely utilized for a variety of reasons, including to 1) anticoagulate patients and help treat and / or prevent thrombosis, 2) maintain patency in artificial blood flow circuits, and 3) anticoagulate blood samples collected for laboratory testing (typically for biochemical assays or blood gas analysis). As such, the presence of UFH is nearly ubiquitous in a hospital setting. Therefore, in laboratory practice, UFH may be present in samples intended for monitoring patients on UFH therapy or intended for biochemical tests, or it may interfere with other (hemostasis) laboratory tests. The aim of this manuscript is to review the role of UFH from the perspective of optimizing laboratory testing to monitor UFH therapy and to avoid or overcome unwanted interference with other laboratory tests.