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The letter addresses concerns regarding the inaccurate definition of Bence Jones proteinuria (BJP) in the EFLM European Urinalysis Guideline 2023. The authors argue that the guideline's terminology does not accurately reflect the characteristics of BJP, which is defined as monoclonal free light chains of immunoglobulins. They caution against using total proteinuria as a screening method for BJP, as it may not be sensitive enough to detect clinically significant concentrations. The authors emphasize the importance of using strict and accurate definitions in guidelines and recommend urine immunofixation as the gold standard test for detecting BJP. [Extracted from the article]

Growing evidence suggests that sustained concentrated urine contributes to chronic metabolic and kidney diseases. Recent results indicate that a daily urinary concentration of 500 mOsm/kg reflects optimal hydration. This study aims at providing personalized advice for daily water intake considering personal intrinsic (age, sex, height, weight) and extrinsic (food and fluid intakes) characteristics to achieve a target urine osmolality (UOsm) of 500 mOsm/kg using machine learning and optimization algorithms. Data from clinical trials on hydration (four randomized and three non-randomized trials) were analyzed. Several machine learning methods were tested to predict UOsm. The predictive performance of the developed algorithm was evaluated against current dietary guidelines. Features linked to urine production and fluid consumption were listed among the most important features with relative importance values ranging from 0.10 to 0.95. XGBoost appeared the most performing approach (Mean Absolute Error (MAE) = 124.99) to predict UOsm. The developed algorithm exhibited the highest overall correct classification rate (85.5%) versus that of dietary guidelines (77.8%). This machine learning application provides personalized advice for daily water intake to achieve optimal hydration and may be considered as a primary prevention tool to counteract the increased incidence of chronic metabolic and kidney diseases. [ABSTRACT FROM AUTHOR]

Appropriateness in Laboratory Medicine has been the object of various types of interventions. From published experiences, it is now clear that to effectively manage the laboratory test demand it is recommended to activate evidence-based preventative strategies stopping inappropriate requests before they can reach the laboratory. To guarantee appropriate laboratory test utilization, healthcare institutions should implement and optimize a computerized provider order entry (CPOE), exploiting the potential of electronic requesting as "enabling factor" for reinforcing appropriateness and sustaining its effects over time. In our academic institution, over the last 15 years, our medical laboratory has enforced various interventions to improve test appropriateness, all directly or indirectly based on CPOE use. The following types of intervention were implemented: (1) applying specific recommendations supported by monitoring by CPOE as well as a continuous consultation with clinicians (tumour markers); (2) removing outdated tests and avoiding redundant duplications (cardiac markers, pancreatic enzymes); (3) order restraints to selected wards and gating policy (procalcitonin, B-type natriuretic peptide, homocysteine); (4) reflex testing (bilirubin fractions, free prostate-specific antigen, aminotransferases, magnesium in hypocalcemia); and (5) minimum retesting interval (D-Dimer, vitamin B12, C-reactive protein, γ-glutamyltranspeptidase). In this paper, we reviewed these interventions and summarized their outcomes primarily related to the changes in total test volumes and cost savings, without neglecting patient safety. Our experience confirmed that laboratory professionals have an irreplaceable role as "stewards" in designing, implementing, evaluating, and maintaining interventions focused to improving test appropriateness. [ABSTRACT FROM AUTHOR]

Purpose: Growing evidence suggests hydration plays a role in metabolic dysfunction, however data in humans are scarce. This study examined the cross-sectional association between hydration and metabolic dysfunction in a representative sample of the US population. Methods: Data from 3961 adult NHANES (National Health and Nutrition Examination Survey) participants (49.8% female; age 46.3 ± 0.5 years) were grouped by quartile of urine specific gravity (USG, 2007–2008 cohort) or urine osmolality (UOsm, 2009–2010 cohort) as measures of hydration. Metabolic dysfunction was assessed by glycemic and insulinemic endpoints and by components of the metabolic syndrome. Multivariate-adjusted linear and logistic regression models were used. Results: Increasing quartiles of USG but not UOsm was associated with higher fasting plasma glucose (FPG), glycated hemoglobin (all P < 0.01), HOMA-IR and elevated insulin (all P < 0.05). Compared with the lowest quartile, those with the highest USG but not UOsm had greater risk of metabolic syndrome (Q4 vs. Q1, OR (99% CI): 1.6 (1.0, 2.7), P = 0.01) and diabetes (Q4 vs. Q1, OR: 1.8 (1.0, 3.4), P < 0.05). Additionally, those with USG > 1.013 or UOsm > 500 mOsm/kg, common cut-off values for optimal hydration based on retrospective analyses of existing data, had less favorable metabolic markers. In a subset of participants free from diabetes mellitus, impaired kidney function, hypertension and diuretic medication, USG remained positively associated with FPG (P < 0.01) and elevated FPG (P < 0.05). Conclusion: These analyses provide population-based evidence that USG as a proxy for hydration is associated with glucose homeostasis in NHANES 2007–2008. The same association was not significant when UOsm was used as a proxy for hydration in the 2009–2010 wave. Clinical trial registry: Not applicable, as this was a reanalysis of existing NHANES data. [ABSTRACT FROM AUTHOR]

Objectives: Procalcitonin (PCT) has been proposed for differentiating viral vs. bacterial infections. In COVID-19, some preliminary results have shown that PCT testing could act as a predictor of bacterial co-infection and be a useful marker for assessment of disease severity. Methods: We studied 83 COVID-19 hospitalized patients in whom PCT was specifically ordered by attending physicians. PCT results were evaluated according to the ability to accurately predict bacterial co-infections and death in comparison with other known biomarkers of infection and with major laboratory predictors of COVID-19 severity. Results: Thirty-three (39.8%) patients suffered an in-hospital bacterial co-infection and 44 (53.0%) patients died. In predicting bacterial co-infection, PCT showed a relatively low accuracy (area under receiver-operating characteristic [ROC] curve [AUC]: 0.757; 95% confidence interval [CI]: 0.651–0.845), with a strength for detecting the outcome not significantly different from that of white blood cell count and C-reactive protein (CRP). In predicting patient death, PCT showed an AUC of 0.815 (CI: 0.714–0.892), not better than those of other more common laboratory tests, such as blood lymphocyte percentage (AUC: 0.874, p=0.19), serum lactate dehydrogenase (AUC: 0.860, p=0.47), blood neutrophil count (AUC: 0.845, p=0.59), and serum albumin (AUC: 0.839, p=0.73). Conclusions: Procalcitonin (PCT) testing, even when appropriately ordered, did not provide a significant added value in COVID-19 patients when compared with more consolidated biomarkers of infection and poor clinical outcome. The major application of PCT in COVID-19 is its ability, associated with a negative predictive value >90%, to exclude a bacterial co-infection when a rule-out cut-off (<0.25 μg/L) is applied. [ABSTRACT FROM AUTHOR]

Sepsis is a life-threatening organ dysfunction caused by a dysregulated response of the host to infection. It represents one of the major health care problems worldwide. Unfortunately, the diagnosis of sepsis is challenging for many reasons, including a lack of a sufficiently sensitive and specific diagnostic test. When procalcitonin (PCT) was discovered, it was thought that it could become the best test for identifying patients with sepsis. From the evidence sources in the available literature, it is now clear that the power of PCT in differentiating infectious from non-infectious forms of systemic inflammatory response syndrome in adults, and in stratifying morbidity and mortality risk, is limited. Nevertheless, PCT determination can be a useful tool for diagnosing late-onset neonatal sepsis, bacterial meningitis and other forms of organ-related bacterial infections and, above all, it can be used for guiding antibiotic stewardship in critical patients. The real impact of this application of PCT testing, however, still needs to be clearly defined. Laboratories should offer unrestricted PCT testing only to intensive care units (as an aid in decision for continuing or stopping antibiotics) and pediatric wards. For all other clinical wards, the laboratory should guide PCT requests and give them support towards the most appropriate approach to testing. • PCT is a poor diagnostic/prognostic marker for sepsis. • PCT is a reliable marker to assist intensivists in the decision to stop antibiotics. • PCT can be useful in pediatrics, but its interpretation can be complicated by some confounding issues. • Vetting of PCT requests by laboratory is recommended to improve appropriateness. [ABSTRACT FROM AUTHOR]

The introduction of "highly sensitive" cardiac troponin assays (hsTn) has reinforced the evidence that only serial testing incorporated in running algorithms allows a more accurate diagnosis of acute myocardial infarction. In this report, we consider the available evidence supporting the use of fast track protocols for ruling out and ruling in non-ST elevation myocardial infarction (NSTEMI) and compare it with the content of recently released guideline by the European Society of Cardiology, noting some uncomfortable aspects that need urgent clarification and/or revision. Firstly, the guideline drafters have to reconsider the available evidence that does not permit to assign the same class and level of evidence to the very well-validated 0-3 h algorithm and to the 0-1 h algorithm. In agreement with the validity of available data, the limitations of fast track protocols, in particular of the 0-1 h algorithm for NSTEMI rule-in, calls for caution. Secondly, as the current diagnostics guidance by the UK National Institute for Health and Care Excellence recommends, rapid diagnostic protocols should be performed only using well-validated hsTn; recommending the use of an assay before being commercially available is not fair and scientifically sound. [ABSTRACT FROM AUTHOR]

During the past decades the healthcare systems have rapidly changed and today hospital care is primarily advocated for critical patients and acute treatments, for which laboratory test results are crucial and need to be always reported in predictably short turnaround time (TAT). Laboratories in the hospital setting can face this challenge by changing their organization from a compartmentalized laboratory department toward a decision making-based laboratory department. This requires the implementation of a core laboratory, that exploits total laboratory automation (TLA) using technological innovation in analytical platforms, track systems and information technology, including middleware, and a number of satellite specialized laboratory sections cooperating with care teams for specific medical conditions. In this laboratory department model, the short TAT for all first-line tests performed by TLA in the core laboratory represents the key paradigm, where no more stat testing is required because all samples are handled in real-time and (auto)validated results dispatched in a time that fulfills clinical needs. To optimally reach this goal, laboratories should be actively involved in managing all the steps covering the total examination process, speeding up also extra-laboratory phases, such sample delivery. Furthermore, to warrant effectiveness and not only efficiency, all the processes, e.g. specimen integrity check, should be managed by middleware through a predefined set of rules defined in light of the clinical governance. [ABSTRACT FROM AUTHOR]

C-reactive protein (CRP) is a cytokine-mediated acute phase reactant with a recognized role in inflammatory conditions and infectious disease. In coronavirus disease 2019 (COVID-19), elevated CRP concentrations in serum were frequently detected and significantly associated with poor outcome in terms of disease severity, need for intensive care, and in-hospital death. For these reasons, the marker was proposed as a powerful test for prognostic classification of COVID-19 patients. In most of available publications, there was however confounding information about how interpretative criteria for CRP in COVID-19 should be derived, including quality of employed assays and optimal cut-off definition. Assuring result harmonization and controlling measurement uncertainty in terms of performance specifications are fundamental to allow worldwide application of clinical information according to specific CRP thresholds and to avoid risk of patient misclassification. [ABSTRACT FROM AUTHOR]

Abstract: The major source of errors producing unreliable laboratory test results is the pre-analytical phase with hemolysis accounting for approximately half of them and being the leading cause of unsuitable blood specimens. Hemolysis may produce interference in many laboratory tests by a variety of biological and analytical mechanisms. Consequently, laboratories need to systematically detect and reliably quantify hemolysis in every collected sample by means of objective and consistent technical tools that assess sample integrity. This is currently done by automated estimation of hemolysis index (HI), available on almost all clinical chemistry platforms, making the hemolysis detection reliable and reportable patient test results more accurate. Despite these advantages, a degree of variability still affects the HI estimate and more efforts should be placed on harmonization of this index. The harmonization of HI results from different analytical systems should be the immediate goal, but the scope of harmonization should go beyond analytical steps to include other aspects, such as HI decision thresholds, criteria for result interpretation and application in clinical practice as well as report formats. With regard to this, relevant issues to overcome remain the objective definition of a maximum allowable bias for hemolysis interference based on the clinical application of the measurements and the management of unsuitable samples. Particularly, for the latter a recommended harmonized approach is required when not reporting numerical results of unsuitable samples with significantly increased HI and replacing the test result with a specific comment highlighting hemolysis of the sample. [Copyright &y& Elsevier]

Abstract: Background: Glycated hemoglobin (HbA1c) has a key role for diagnosing diabetes and monitoring glycemic state. As recently reviewed, available data on HbA1c biological variation show marked heterogeneity. Here we experimentally revaluated these data using a well designed protocol. Methods: We took five EDTA whole blood specimens from 18 apparently healthy subjects on the same day, every two weeks for two months. Samples were stored at −80°C until analysis and assayed in duplicate in a single run by Roche Tina-quant® Gen.2 immunoassay. Data were analyzed by the ANOVA. To assess the assay traceability to the IFCC reference method, we preliminarily carried out a correlation experiment. Results: The bias (mean±SD) of the Roche immunoassay was 0.3%±0.7%, confirming the traceability of the employed assay. No difference was found in HbA1c values between men and women. Within- and between-subject CV were 2.5% and 7.1%, respectively. Derived desirable analytical goals for imprecision, bias, and total error resulted 1.3%, 1.9%, and 3.9%, respectively. HbA1c had marked individuality, limiting the use of population-based reference limits for test interpretation. The estimated critical difference was ~10%. Conclusions: For the first time we defined biological variation and derived indices for the clinical application of HbA1c measurements using an accurately designed protocol and an assay standardized according to the IFCC. [Copyright &y& Elsevier]

Abstract: Background: The measurement of glycated hemoglobin (HbA1c) has a pivotal role in monitoring glycemic state in diabetic patients. Furthermore, the American Diabetes Association has recently recommended the use of HbA1c for diabetes diagnosis, but a clear definition of the clinically allowable measurement error is still lacking. Information on biological variability of the analyte can be used to achieve this goal. Methods: We systematically reviewed the published studies on the biological variation of HbA1c to check consistency of available data in order to accurately define analytical goals. Results: The nine recruited studies were limited by choice of analytic methodology, population selection, protocol application and statistical analyses. Conclusions: There is an urgent need to determine biological variability of HbA1c using a specific and traceable assay, appropriate protocol and appropriate statistical evaluation of data. [ABSTRACT FROM AUTHOR]

Background: Monitoring of test imprecision is one of the most important quality indicators in clinical laboratories. Imprecision goals should be derived from biological variation. The aim of this study was to evaluate the imprecision of eight tumour biomarker assays routinely measured on the Modular E170 system. Methods: Method coefficient of variations (CVs) were obtained by an appropriate Internal Quality Control programme based on the measurement every working day of a fresh-frozen human serum pool with biomarkers concentrations around the clinical cut-offs. We evaluated data collected along the whole year 2008 (n range: 21-461); monthly CVs and their cumulative means were calculated and compared with corresponding goals. Results: Biomarkers concentration means and average yearly CVs (desirable goals in parentheses) were as follows: α-fetoprotein, 9.6 μg/L, 3.9% (6.0%); CA125, 41.2 U/L, 2.8% (12.4%); CA15.3, 32.7 U/L, 3.1% (3.1%); CA19.9, 35.1 U/L, 2.8% (8.0%); CEA, 7.7 μg/L, 4.3% (6.4%); prostate-specific antigen (PSA), 4.1 μg/L, 4.3% (9.1%); CYFRA 21.1, 2.4 μg/L, 5.7% (11.3%); and ferritin, 64.5 μg/L, 4.0% (7.1%). Conclusions: Our study shows that in routine laboratory practice and over a clinically and analytically relevant time-span, the imprecision of the tumour biomarker measurements on the Roche Modular E170 fulfills desirable goals. For four assays (CA125, CA19.9, PSA and CYFRA 21.1) the optimum CV can even be achieved. [ABSTRACT FROM AUTHOR]

Results are automatically calculated by the system as follows: HbA SB 1c sb (mmol/mol)=[HbA SB 1c sb ( mol/L)/total haemoglobin (mol/L)] × 1,000. A bias >1 mmol/mol for Alinity became however evident only in samples with HbA SB 1c sb values >=69 mmol/mol. Keywords: clinical governance; diabetes; HbA1c; metrological traceability; total laboratory automation EN clinical governance diabetes HbA1c metrological traceability total laboratory automation 441 450 10 02/07/22 20220201 NES 220201 Introduction There are approximately 500 million people living with diabetes mellitus (DM) worldwide [[1]]. Alinity showed a mean positive absolute bias of 0.54 mmol/mol (range: -0.4 to 2.6 mmol/mol), corresponding to a mean percentage difference of 0.87% (range: -1.13 to 2.74%). [Extracted from the article]

Previous studies reported lipase elevations in serum of COVID-19 patients trying to establish a causal link between SARS-CoV-2 infection and pancreatic damage. However, the degree and prevalence of hyperlipasemia was not uniform across studies. We retrospectively evaluated 1,092 hospitalized patients with COVID-19 and at least one available lipase result. The number and frequency of patients with lipase above the upper reference limit (URL), >3 URL, and >6 URL were estimated. Correlations between lipase values and other biomarkers of organ or tissue damage were performed to identify possible extra-pancreatic sources of lipase release. The potential prognostic role of lipase to predict death and intensive care unit (ICU) admission during hospitalization was also evaluated. Lipase was >URL in 344 (31.5%) of COVID-19 patients. Among them, 65 (5.9%) and 25 (2.3%) had a peak lipase >3 URL and >6 URL, respectively. In the latter group, three patients had acute pancreatitis of gallstone or drug-induced etiology. In others, the etiology of lipase elevations appeared multifactorial and could not be directly related to SARS-CoV-2 infection. No correlation was found between lipase and other tested biomarkers of organ and tissue damage. Lipase concentrations were not different between survivors and non-survivors; however, lipase was significantly increased (p<0.001) in patients admitted to the ICU, even if the odds ratio for lipase as predictor of ICU admission was not significant. Lipase was elevated in ∼1/3 of COVID-19 patients, but the clinical significance of this finding is unclear and irrelevant to patient prognosis during hospitalization. [ABSTRACT FROM AUTHOR]

Elevated copeptin, a surrogate marker of vasopressin, is linked to low water intake and increased diabetes risk. Water supplementation in habitual low-drinkers with high copeptin significantly lowers both fasting plasma (fp) copeptin and glucose. This study aims at investigating possible underlying mechanisms. Thirty-one healthy adults with high copeptin (> 10.7 pmol·L−1 (men), > 6.1 pmol−1 (women)) and 24-h urine volume of < 1.5L and osmolality of > 600 mOsm·kg−1 were included. The intervention consisted of addition of 1.5 L water daily for 6 weeks. Fp-adrenocorticotropic hormone (ACTH), fp-cortisol, 24-h urine cortisol, fasting and 2 h (post oral glucose) insulin and glucagon were not significantly affected by the water intervention. However, decreased (Δ baseline-6 weeks) fp-copeptin was significantly associated with Δfp-ACTH (r = 0.76, p < 0.001) and Δfp-glucagon (r = 0.39, p = 0.03), respectively. When dividing our participants according to baseline copeptin, median fp-ACTH was reduced from 13.0 (interquartile range 9.2–34.5) to 7.7 (5.3–9.9) pmol L−1, p = 0.007 in the top tertile of copeptin, while no reduction was observed in the other tertiles. The glucose lowering effect from water may partly be attributable to decreased activity in the hypothalamic–pituitary–adrenal axis. ClinicalTrials.gov: NCT03574688. [ABSTRACT FROM AUTHOR]

• The management strategy of affected results in haemolysed samples is widely debated. • A dedicated approach tailored to the characteristics of young patients is desirable. • We propose an alternative approach for laboratory reports of paediatric wards. • Our report can act as a driving force for improving the phlebotomy quality. The management of affected results in haemolysed samples (HS) is debated. In an infant-maternity setting, for reporting interfered test results, we provided the result itself, the degree of haemolysis (as free haemoglobin concentration), and a warning recommending sample recollection. We investigated the impact of this approach on sample quality and clinicians' decision-making. Free haemoglobin was measured on Beckman Coulter AU680 as haemolytic index. We estimated the total HS number, the clinical wards more affected by HS, the most interfered analytes, and the retesting rate of interfered tests, by comparing data from Apr-Dec 2017, the period just after the introduction of the new policy, vs. Apr-Dec 2018. One year after the new report introduction, a significant HS decrease (5.8% vs. 7.8%, P < 0.001) was detected, together with a reduction of the frequency by which haemolysis affected results. The most affected wards, i.e., Paediatric and Neonatal Intensive Care Units, showed an improvement in sample quality (HS rate, 30.6% to 16.1%, P < 0.001, and 25.2% to 20.9%, P = 0.048, respectively). We noted a significant decrease in retesting after an alerted result for aspartate aminotransferase, magnesium, potassium, conjugated bilirubin, and lactate dehydrogenase. Our approach led to a HS decrease, suggesting that the provided report could be a driving force for improvement of phlebotomy quality, also helping clinicians in deciding if retesting is essential or not. [ABSTRACT FROM AUTHOR]

Plenty of studies demonstrate that hospital-acquired anemia (HAA) can increase transfusion rates, mortality, morbidity and cause unnecessary patient burden, including additional length of hospital stay, sleep disruption and venipuncture harms resulting from blood samples unlikely to change clinical management. Beyond patient costs, community costs should also be considered, such as laboratory time and resources waste, environmental impact, increasing pressure on labs and fewer tests available on time for patients who can benefit from them most. Blood over-testing does not support the principles of non-maleficence, justice and respect for patient autonomy, at the expense dubious beneficence. Reducing the number and frequency of orders is possible, to a certain extent, by adopting nudge strategies and raising awareness among prescribing doctors. However, reducing the orders may appear unsafe to doctors and patients. Therefore, reducing blood volume from each order is a better alternative, which is worth implementing through technological, purchasing and organizational arrangements, possibly combined according to need (smaller tubes, adequate analytic platforms, blind dilution, blood conservative devices, aggregating tests and laboratory units). [ABSTRACT FROM AUTHOR]

This letter to the editor addresses the issue of incomplete information provided by manufacturers regarding the metrological traceability of in vitro diagnostic calibrators, using plasma ethanol as an example. The authors argue that this lack of transparency can hinder accurate measurement in laboratories. They provide examples of manufacturers who do not disclose the traceability of their calibrators. The authors stress the importance of accurate information and measurement uncertainty estimation for identifying analytical limitations and improving standardization. The document includes references to scientific articles and resources related to analytical performance specifications and calibration of breath alcohol analyzers, which may be helpful for library patrons researching forensic science or alcohol analysis. [Extracted from the article]

No Abstract available [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about heat-shock proteins.

This article discusses the importance of appropriate laboratory test orders in order to prevent misdiagnosis, incorrect treatment, and negative outcomes for patients. The authors highlight a study that introduced a decision support alert to improve compliance with clinical guidelines for ordering serum protein electrophoresis pattern (SPEP) testing with a concurrent serum free light chain (sFLC) measurement. The study found that the alert led to increased compliance and the identification of new diagnoses. However, the authors also acknowledge the potential for overordering if an order set defaults both SPEP and sFLC tests. The authors then present their own experience in verifying the appropriateness of sFLC orders in their academic institution, finding that 10-15% of orders were inappropriate. They suggest the need for specific interventions to reduce inappropriate orders, such as algorithmic approaches. [Extracted from the article]

The letter published in the Annals of Clinical Biochemistry discusses the impact of the Hub & Spoke organization on the measurement of plasma ammonia levels. The study conducted a retrospective analysis comparing results from outpatients and inpatients, revealing differences in haemolysis index values and sample handling protocols. As a result of the findings, the authors revised their ammonia testing procedures within the organization to ensure efficient sample delivery, rapid analysis, and appropriate result reporting. Age-related reference intervals will also be implemented in the future. [Extracted from the article]

This is vital in order to assure the correct differentiation, after a single hs-cTn measurement at ED admission, between patients with a negligible risk of cardiac adverse events who are potentially suitable for immediate discharge and those needing further evaluation in order to exclude/confirm AMI. Therefore, manufacturers of hs-cTn measuring systems should be encouraged to provide quality control materials that cover all the clinically relevant concentrations of the analyte, including those close to the LOD to monitor baseline drifts. [Extracted from the article]

Selecting appropriate laboratory tests based on available evidence is central to improve clinical effectiveness and impacting on patient outcome. Although long studied, there is no mutual agreement upon pleural fluid (PF) management in the laboratory context. Given the experienced confusion about the real contribution of laboratory investigations to guide clinical interpretation, in this update, we tried to identify useful tests for the PF analysis, aiming to unravel critical points and to define a common line in requesting modalities and practical management. We performed a careful literature review and a deepened study on available guidelines to finalize an evidence-based test selection, intended for clinicians' use to streamline PF management. The following tests depicted the basic PF profile routinely needed: (1) abbreviated Light's criteria (PF/serum total protein ratio and PF/serum lactate dehydrogenase ratio) and (2) cell count with differential analysis of haematological cells. This profile fulfils the primary goal to determine the PF nature and discriminate between exudative and transudative effusions. In specific circumstances, clinicians may consider additional tests as follows: the albumin serum to PF gradient, which reduces exudate misclassification rate by Light's criteria in patients with cardiac failure assuming diuretics; PF triglycerides, in differentiating chylothorax from pseudochylothorax; PF glucose, for identification of parapneumonic effusions and other causes of effusion, such as rheumatoid arthritis and malignancy; PF pH, in suspected infectious pleuritis and to give indications for pleural drainage; and PF adenosine deaminase, for a rapid detection of tuberculous effusion. [ABSTRACT FROM AUTHOR]

This study systematically examined the influence of carbohydrate (sucrose), sodium, and caffeine on the fluid retention potential of beverages under euhydrated conditions, using the beverage hydration index method. Three cohorts, each of 12 young, healthy, active men, ingested 1 L of beverages containing four different concentrations of a single component (sucrose, sodium, or caffeine) in a double-blind, crossover manner. Urine output was collected for the subsequent 4 hr. Cumulative urine output was lower and net fluid balance was higher after 10 and 20% sucrose beverages than 0 and 5% sucrose beverages (p <.05), and after 27 and 52 mmol/L sodium beverages than 7 and 15 mmol/L sodium beverages (p <.05). No difference in urine output or net fluid balance was apparent following ingestion of caffeine at concentrations of 0–400 mg/L (p =.83). Consequently, the calculated beverage hydration index was greater in beverages with higher sucrose or sodium content, but caffeine had no effect. No difference was observed in arginine vasopressin or aldosterone between any trials. These data highlight that the key drivers promoting differences in the fluid retention potential of beverages when euhydrated are energy density, likely through slowed fluid delivery to the circulation (carbohydrate content effect), or electrolyte content through improved fluid retention (sodium content effect). These data demonstrate that beverage carbohydrate and sodium content influence fluid delivery and retention in the 4 hr after ingestion, but caffeine up to 400 mg/L does not. Athletes and others can use this information to guide their daily hydration practices. [ABSTRACT FROM AUTHOR]

Abstract: Determination of serum soluble transferrin receptor (sTfR) has been proposed to identify iron-deficiency anemia (IDA) in patients affected by concurrent inflammatory disease that may spuriously increase ferritin concentration. The aim of this study was to critically review the available literature to assess the diagnostic efficacy of sTfR in complicated anemia. The criteria for study selection were: enrolment of patients with complicated anemia; bone marrow examination used as diagnostic gold standard for IDA; evaluation of sTfR vs. ferritin and binary data presentation. Six published studies met the criteria. However, the small size and wide heterogeneity of the studies did not allow us to conduct a meta-analysis. sTfR was overall more sensitive, even though it was evident that the ferritin sensitivity was influenced by selected cut-offs. Well-designed studies are still needed to define the added value, if any, of sTfR to ferritin for IDA detection in complicated anemia. [Copyright &y& Elsevier]

Purpose: It remains unclear whether exercise-induced muscle damage (EIMD) increases heat strain during subsequent exercise heat stress, which in turn may increase the risk of exertional heat illness. We examined heat strain during exercise heat stress 30 min after EIMD to coincide with increases in circulating pyrogens (e.g., interleukin-6 [IL-6]) and 24 h after EIMD to coincide with the delayed muscle inflammatory response when a higher rate of metabolic energy expenditure (Ṁ) and thus decreased economy might also increase heat strain. Methods: Thirteen non-heat-acclimated males (mean ± SD, age = 20 ± 2 yr) performed exercise heat stress tests (running for 40 min at 65% ̇VO2max in 33°C, 50% humidity) 30 min (HS1) and 24 h (HS2) after treatment, involving running for 60 min at 65% ̇VO2max on either −10% gradient (EIMD) or +1% gradient (CON) in a crossover design. Rectal (Tre) and skin (Tsk) temperature, local sweating rate, and Ṁ were measured throughout HS tests. Results: Compared with CON, EIMD evoked higher circulating IL-6 pre-HS1 (P < 0.01) and greater plasma creatine kinase and muscle soreness pre-HS2 (P < 0.01). The ΔTre was greater after EIMD than CON during HS1 (0.35°C, 95% confidence interval = 0.11°C-0.58°C, P < 0.01) and HS2 (0.17°C, 95% confidence interval = 0.07°C-0.28°C, P < 0.01). Ṁ was higher on EIMD throughout HS1 and HS2 (P < 0.001). Thermoeffector responses (Tsk, sweating rate) were not altered by EIMD. Thermal sensation and RPE were higher on EIMD after 25 min during HS1 (P < 0.05). The final Tre during HS1 correlated with the pre-HS1 circulating IL-6 concentration (r = 0.67). Conclusions: Heat strain was increased during endurance exercise in the heat conducted 30 min after and, to a much lesser extent, 24 h after muscle-damaging exercise. These data indicate that EIMD is a likely risk factor for exertional heat illness particularly during exercise heat stress when behavioral thermoregulation cues are ignored. [ABSTRACT FROM AUTHOR]

Junglee NA, Di Felice U, Dolci A, Fortes MB, Jibani MM, Lemmey AB, Walsh NP, Macdonald JH. Exercising in a hot environment with muscle damage: effects on acute kidney injury biomarkers and kidney function. Am J Physiol Renal Physiol 305: F813-F820, 2013. First published July 3, 2013; doi:10.1152/ajprenal.00091.2013.--Unaccustomed strenuous physical exertion in hot environments can result in heat stroke and acute kidney injury (AKI). Both exercise-induced muscle damage and AKI are associated with the release of interleukin- 6, but whether muscle damage causes AKI in the heat is unknown. We hypothesized that muscle-damaging exercise, before exercise in the heat, would increase kidney stress. Ten healthy euhydrated men underwent a randomized, crossover trial involving both a 60-min downhill muscle-damaging run (exercise-induced muscle damage; EIMD), and an exercise intensity-matched non-muscle-damaging flat run (CON), in random order separated by 2 wk. Both treatments were followed by heat stress elicited by a 40-min run at 33°C. Urine and blood were sampled at baseline, after treatment, and after subjects ran in the heat. By design, EIMD induced higher plasma creatine kinase and interleukin-6 than CON. EIMD elevated kidney injury biomarkers (e.g., urinary neutrophil gelatinase-associated lipocalin (NGAL) after a run in the heat: EIMD-CON, mean difference [95% CI]: 12 [5, 19] ng/ml) and reduced kidney function (e.g., plasma creatinine after a run in the heat: EIMD-CON, mean difference [95% CI]: 0.2 [0.1, 0.3] mg/dl), where CI is the confidence interval. Plasma interleukin-6 was positively correlated with plasma NGAL (r 0.9, P 0.001). Moreover, following EIMD, 5 of 10 participants met AKIN criteria for AKI. Thus for the first time we demonstrate that muscle-damaging exercise before running in the heat results in a greater inflammatory state and kidney stress compared with non-muscle-damaging exercise. Muscle damage should therefore be considered a risk factor for AKI when performing exercise in hot environments. [ABSTRACT FROM AUTHOR]

Determination of serum soluble transferrin receptor (sTfR) is proposed to distinguish between iron-deficiency anemia and anemia of chronic disease. Here we conducted a meta-analysis of the literature to evaluate the diagnostic efficacy of sTfR and sTfR/log ferritin index. The meta-analysis included 18 sTfR and 10 sTfR index studies. Three sTfR index studies were, however, eliminated as outliers. The odds ratio was significant for both sTfR (22.9, 95% confidence interval [CI], 9.6-55.0) and sTfR index (9.5, 95% CI, 5.0-18.1) in a heterogeneous set of studies. Meta-analysis for sensitivity, specificity, and likelihood ratios (LRs) was performed only in a subset of 10 sTfR studies. The overall sensitivity, specificity, and positive and negative LRs were 86%, 75%, 3.85, and 0.19, respectively, with an area under summary receiver operating characteristic curve of 0.912 (standard error, 0.039). Additional studies are needed to define the overall diagnostic accuracy of sTfR. [ABSTRACT FROM AUTHOR]

The purpose of measurement standardization is to achieve closer comparability of results obtained using different commercial systems. Regarding serum protein immunoassays, a reference preparation (BCR-470) was released in 1993 and adopted by manufacturers across the world to value-assign their assay calibrators for routine methods to reduce method-dependent variation. Moving from nephelometric (Beckman Immage 800) to turbidimetric determination (Roche Cobas c 501) of seven serum proteins, we preliminarily checked the comparability of results between the two systems. The study was performed according to the CLSI EP9-A protocol on 30 fresh sera, tested on each system in duplicate, and subdivided on two different days, without recalibration and using manufacturers’ control materials to validate the runs. Both manufacturers’ package inserts provide statements that kit calibrators are traceable to BCR-470. Suggested reference intervals are also the same. Although a fairly good correlation was observed ( r = 0.955), the comparison of ceruloplasmin methods produced evidence of highly significant proportional (regression slope, 0.572) and constant bias (intercept, 0.05 g/L). Absolute and percentage mean differences were −0.11 g/L (95% confidence interval (CI) −0.13 to −0.10 g/L) and −39.1% (CI −43.1 to −35.2%), respectively. No other evaluated proteins showed similar problems. Lacking a ceruloplasmin reference method, it is impossible to demonstrate that one of the two assays produces true ceruloplasmin values. The problem is, however, that results coming from the two assays are clearly not comparable. This may be either due to a lack of commutability of the reference material with biological samples in the evaluated assays or to calibration problems by manufacturers in one of the stages of the calibration hierarchy. [ABSTRACT FROM AUTHOR]

Background: Multisystem inflammatory syndrome in children (MIS-C) is a novel condition temporally associated with SARS-CoV2 infection. Cardiovascular involvement is mainly evident as acute myocardial dysfunction in MIS-C. The aim of this study was to describe the cardiac dysfunction in patients with MIS-C, defining the role of severity in the clinical presentations and outcomes in a single cohort of pediatric patients. Methods: A single-center retrospective study on patients diagnosed with MIS-C, according to the Center for Disease Control and Prevention (CDC) definition, and referred to Vittore Buzzi Children's Hospital in Milan from November 2020 to February 2021. Patients were managed according to a local approved protocol. According to the admission cardiac left ventricular ejection fraction (LVEF), the patients were divided into group A (LVEF < 45%) and group B (LVEF ≥45%). Pre-existing, clinical, and laboratory factors were assessed for evaluating outcomes at discharge. Results: Thirty-two patients were considered. Cardiac manifestations of MIS-C were reported in 26 patients (81%). Group A included 10 patients (9 M/1F, aged 13 years [IQR 5–15]), and group B included 22 patients (15 M/7 M, aged 9 years [IQR 7–13]). Significant differences were noted among clinical presentations (shock, diarrhea, intensive care unit admission), laboratory markers (leucocytes, neutrophils, and protein C-reactive), and cardiac markers (troponin T and N-terminal pro B-type Natriuretic Peptide) between the groups, with higher compromission in Group A. We found electrocardiogram anomalies in 14 patients (44%) and rhythm alterations in 3 patients (9%), without differences between groups. Mitral regurgitation and coronary involvement were more prevalent in group A. Total length of hospital stay and cardiac recovery time were not statistically different between groups. A recovery of cardiac functioning was reached in all patients. Conclusion: Despite significant differences in clinical presentations and need for intensive care, all of the MIS-C patients with significant cardiac involvement in this study completely recovered. This suggests that the heart is an involved organ and did not influence prognosis if properly treated and supported in the acute phase. [ABSTRACT FROM AUTHOR]

• Aspartate aminotransferase (AST) is often increased in COVID-19 patients. • Increases of AST in COVID-19 can be explained by summing the effects of hepatocellular injury and muscle damage. • The mechanisms for abnormal AST in COVID-19 are likely multifactorial. • The clinical significance of AST elevations in COVID-19 remains unclear. Aspartate aminotransferase (AST) is often increased in COVID-19 and, in some studies, AST abnormalities were associated with mortality risk. 2054 hospitalized COVID-19 patients were studied. To identify sources of AST release, correlations between AST peak values and other biomarkers of tissue damage, i.e., alanine aminotransferase (ALT) for hepatocellular damage, creatine kinase (CK) for muscle damage, lactate dehydrogenase for multiorgan involvement, alkaline phosphatase and γ-glutamyltransferase for cholestatic injury, and C-reactive protein (CRP) for systemic inflammation, were performed and coefficients of determination estimated. The role of AST to predict death and intensive care unit admission during hospitalization was also evaluated. All measurements were performed using standardized assays. AST was increased in 69% of patients. Increases could be fully explained by summing the effects of hepatocellular injury [AST dependence from ALT, 66.8% [95% confidence interval (CI): 64.5–69.1)] and muscle damage [AST dependence from CK, 42.6% (CI: 39.3–45.8)]. We were unable to demonstrate an independent association of AST increases with worse outcomes. The mechanisms for abnormal AST in COVID-19 are likely multifactorial and a status related to tissue suffering could play a significant role. The clinical significance of AST elevations remains unclear. [ABSTRACT FROM AUTHOR]

Purpose: An increasing body of evidence suggests that excreting a generous volume of diluted urine is associated with short- and long-term beneficial health effects, especially for kidney and metabolic function. However, water intake and hydration remain under-investigated and optimal hydration is poorly and inconsistently defined. This review tests the hypothesis that optimal chronic water intake positively impacts various aspects of health and proposes an evidence-based definition of optimal hydration. Methods: Search strategy included PubMed and Google Scholar using relevant keywords for each health outcome, complemented by manual search of article reference lists and the expertise of relevant practitioners for each area studied. Results: The available literature suggest the effects of increased water intake on health may be direct, due to increased urine flow or urine dilution, or indirect, mediated by a reduction in osmotically -stimulated vasopressin (AVP). Urine flow affects the formation of kidney stones and recurrence of urinary tract infection, while increased circulating AVP is implicated in metabolic disease, chronic kidney disease, and autosomal dominant polycystic kidney disease. Conclusion: In order to ensure optimal hydration, it is proposed that optimal total water intake should approach 2.5 to 3.5 L day−1 to allow for the daily excretion of 2 to 3 L of dilute (< 500 mOsm kg−1) urine. Simple urinary markers of hydration such as urine color or void frequency may be used to monitor and adjust intake. [ABSTRACT FROM AUTHOR]

Background: Recent international recommendations for the diagnosis of gestational diabetes (GD) were implemented in a university hospital. The aim was to audit the appropriateness of use of the new diagnostic approach. Methods: The same 5-month period, one before [2009, traditional two-step oral glucose tolerance test (OGTT) approach, S1] and one after the implementation of new criteria (2010, S2) were compared. Results: In the two periods, 256 (S1) and 245 (S2) pregnant women were examined and 298 (50 g, n=195; 100 g, n=103) and 252 (75 g) OGTTs were, respectively, executed. In S1, 54 (27.7%) 50 g OGTTs resulted positive and 36 (66.7%) of those performed the 100 g OGTT. In addition, three (1.5% of total) 50 g OGTT negative women were submitted to 100 g OGTT. Sixty-three women did 100 g OGTT only. In total, 14 (13.6%) 100 g OGTTs were positive. In S2, 38 (15.1%) 75 g OGTTs were positive. In women who did the complete protocol in the hospital, 98.3% in S1 and 77.0% in S2 performed the correct protocol (p<0.0001). Conclusions: In this hospital new recommendations for GD diagnosis are not correctly applied in 23% of cases. The main issue seems to be the lack of consideration of the new threshold for fasting glycemia (5.1 mmol/L) as a main decisional driver for performing OGTT. [ABSTRACT FROM AUTHOR]

Context.--A relevant portion of coronavirus disease 2019 (COVID-19) patients develop severe disease with negative outcomes. Several biomarkers have been proposed to predict COVID-19 severity, but no definite interpretative criteria have been established to date for stratifying risk. Objective.--To evaluate 6 serum biomarkers (C-reactive protein, lactate dehydrogenase, D-dimer, albumin, ferritin, and cardiac troponin T) for predicting COVID-19 severity and to define related cutoffs able to aid clinicians in risk stratification of hospitalized patients. Design.--A retrospective study of 427 COVID-19 patients was performed. Patients were divided into groups based on their clinical outcome: nonsurvivors versus survivors and patients admitted to an intensive care unit versus others. Receiver operating characteristic curves and likelihood ratios were employed to define predictive cutoffs for evaluated markers. Results.--Marker concentrations at peak were signifi significantly different between groups for both selected outcomes. At univariate logistic regression analysis, all parameters were significantly associated with higher odds of death and intensive care. At the multivariate analysis, high concentrations of lactate dehydrogenase and low concentrations of albumin in serum remained significantly associated with higher odds of death, whereas only low lactate dehydrogenase activities remained associated with lower odds of intensive care admission. The best cutoffs for death prediction were greater than 731 U/L for lactate dehydrogenase and 18 g/L or lower for albumin, whereas a lactate dehydrogenase activity lower than 425 U/L was associated with a negative likelihood ratio of 0.10 for intensive treatment. Conclusions.--Our study identifies which biochemistry tests represent major predictors of COVID-19 severity and defines the best cutoffs for their use. [ABSTRACT FROM AUTHOR]

Purpose: This investigation had three purposes: (a) to evaluate changes in hydration biomarkers in response to a graded rehydration intervention (GRHI) following 3 days of water restriction (WR), (b) assess within-day variation in urine concentrations, and (c) quantify the volume of fluid needed to return to euhydration as demonstrated by change in Ucol. Methods: 115 adult males and females were observed during 1 week of habitual fluid intake, 3 days of fluid restriction (1000 mL day−1), and a fourth day in which the sample was randomized into five different GRHI groups: no additional water, CON; additional 500 mL, G+0.50; additional 1000 mL, G+1.00; additional 1500 mL, G+1.50; additional 2250 mL, G+2.25. All urine was collected on 1 day of the baseline week, during the final 2 days of the WR, and during the day of GRHI, and evaluated for urine osmolality, color, and specific gravity. Results: Following the GRHI, only G+1.50 and G+2.25 resulted in all urinary values being significantly different from CON. The mean volume of water increase was significantly greater for those whose Ucol changed from > 4 to < 4 (+ 1435 ± 812 mL) than those whose Ucol remained ≥ 4 (+ 667 ± 722 mL, p < 0.001). Conclusions: An additional 500 mL of water is not sufficient, while approximately 1500 mL of additional water (for a total intake between 2990 and 3515 mL day−1) is required to return to a urine color associated with adequate water intake, following 3 days of WR. [ABSTRACT FROM AUTHOR]

The immunohistochemistry was negative for human chorionic gonadotropin (hCG) subunit, even in the areas with intratubular neoplasia. At admission, serum AFP was undetectable, total hCG (Elecsys "hCG+ " assay, Roche Diagnostics) was 30 U/L (recommended cut-off for men <50 years, 0.3 U/L) and lactate dehydrogenase (LDH) 898 U/L (upper reference limit [URL], 220 U/L). We observed that the behavior of LDH and hCG+ paralleled, and the hCG+ peak at 1.1 U/L was anticipated of 1 week by a sudden increase in LDH (547 U/L). At admission of the patient, clinicians erroneously ordered the hCG Abbott, so laboratory professionals corrected the request and then recommended the ordering of hCG+ Roche for further evaluation. [Extracted from the article]

Background: Blood loss for laboratory testing may contribute to hospital-acquired anemia. When implementing the core laboratory (core-lab) section, we consolidated first-line tests decreasing the number of tubes previously dispatched to different sites. Here, hypothesized benefits of the amount of blood volume drawn were explored. Methods: We retrieved, using a laboratory information system (LIS), the number of tubes received by laboratories interested in the change from all clinical wards in a year-based period, i.e. 2013 for pre-core-lab and 2015 for core-lab system, respectively. Data were expressed as the overall number of tubes sent to laboratories, the corresponding blood volume, and the number of laboratory tests performed, normalized for the number of inpatients. Results: After consolidation, the average number of blood tubes per inpatient significantly decreased (12.6 vs. 10.7, p < 0.001). However, intensive care units (ICUs) did not reduce the number of tubes per patient, according to the needs of daily monitoring of their clinical status. The average blood volume sent to laboratories did not vary significantly because serum tubes for core-lab required higher volumes for testing up to 55 analytes in the same transaction. Finally, the number of requested tests per patient during the new osystem slightly decreased (−2.6%). Conclusions: Total laboratory automation does not automatically mean reducing iatrogenic blood loss. The new system affected the procedure of blood drawing in clinical wards by significantly reducing the number of handled tubes, producing a benefit in terms of costs, labor and time consumption. Except in ICUs, this also slightly promoted some blood saving. ICUs which engage in phlebotomizing patients daily, did not take advantage from the test consolidation. [ABSTRACT FROM AUTHOR]

Keywords: D-dimer; minimum retesting interval; testing appropriateness EN D-dimer minimum retesting interval testing appropriateness e175 e176 2 06/21/22 20220701 NES 220701 To the Editor, We read with great interest the review by Lang updating the experience about the application of the minimum retesting interval (MRI) concept [[1]]. For evaluating the efficacy and cost-effectiveness of this intervention, we collected data from laboratory information system about numbers of requested D-dimer tests through the same 9 month period (March-November 2017 vs. 2018), before and after the CPOE-based intervention. [Extracted from the article]

The article presents a study which examined the efficacy of using a Sysmex XN-9000 hematology system based on white blood cells (WBC), red blood cells (RBC), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), men corpuscular hemoglobin concentration (MCHC) and platelets (PLT). The parameters used for the material include stabilized lysable human RBC, simulated PLT components, and whole-blood sample. The commutability results for the material are described.

Aims: Acute mountain sickness (AMS) develops when the body fails to acclimatize to atmospheric changes at altitude. Preascent prediction of susceptibility to AMS would be a useful tool to prevent subsequent harm. Changes to peripheral oxygen saturation (SpO2) on hypoxic exposure have previously been shown to be of poor predictive value. Heart rate variability (HRV) has shown promise in the early prediction of AMS, but its use pre-expedition has not previously been investigated. We aimed to determine whether pre- and intraexpedition HRV assessment could predict susceptibility to AMS at high altitude with better diagnostic accuracy than SpO2. Methods: Forty-four healthy volunteers undertook an expedition in the Nepali Himalaya to >5000 m. SpO2 and HRV parameters were recorded at rest in normoxia and in a normobaric hypoxic chamber before the expedition. On the expedition HRV parameters and SpO2 were collected again at 3841 m. A daily Lake Louise Score was obtained to assess AMS symptomology. Results: Low frequency/high frequency (LF/HF) ratio in normoxia (cutpoint ≤2.28 a.u.) and LF following 15 minutes of exposure to normobaric hypoxia had moderate (area under the curve ≥0.8) diagnostic accuracy. LF/ HF ratio in normoxia had the highest sensitivity (85%) and specificity (88%) for predicting AMS on subsequent ascent to altitude. In contrast, pre-expedition SpO2 measurements had poor (area under the curve <0.7) diagnostic accuracy and inferior sensitivity and specificity. Conclusions: Pre-ascent measurement of HRV in normoxia was found to be of better diagnostic accuracy for AMS prediction than all measures of HRV in hypoxia, and better than peripheral oxygen saturation monitoring. [ABSTRACT FROM AUTHOR]

Background Automatic photometric determination of the hemolysis index (HI) on serum and plasma samples is central to detect potential interferences of in vitro hemolysis on laboratory tests. When HI is above an established cut-off for interference, results may suffer from a significant bias and undermine clinical reliability of the test. Despite its undeniable importance for patient safety, the analytical performance of HI estimation is not usually checked in laboratories. Here we evaluated for the first time the random source of measurement uncertainty of HI determination on the two Abbott Architect c16000 platforms in use in our laboratory. Methods From January 2016 to September 2017, we collected data from daily photometric determination of HI on a fresh-frozen serum pool with a predetermined HI value of ~ 100 (corresponding to ~ 1 g/L of free hemoglobin). Monthly and cumulative CVs were calculated. Results During 21 months, 442 and 451 measurements were performed on the two platforms, respectively. Monthly CVs ranged from 0.7% to 2.7% on c16000–1 and from 0.8% to 2.5% on c16000-2, with a between-platform cumulative CV of 1.82% (corresponding to an expanded uncertainty of 3.64%). Mean HI values on the two platforms were just slightly biased (101.3 vs. 103.1, 1.76%), but, due to the high precision of measurements, this difference assumed statistical significance (p < 0.0001). Conclusions Even though no quality specifications are available to date, our study shows that the HI measurement on Architect c16000 platform has nice reproducibility that could be considered in establishing the state of the art of the measurement. [ABSTRACT FROM AUTHOR]