Blood over-testing: impact, ethical issues and mitigating actions.

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).

Fish Intake in Relation to Fatal and Non-Fatal Cardiovascular Risk: A Systematic Review and Meta-Analysis of Cohort Studies.

Epidemiological studies have shown that eating fish significantly reduces cardiovascular disease (CVD) incidence and mortality. However, more focused meta-analyses based on the most recent results from prospective cohort studies are needed. This systematic review and meta-analysis aims to update the association between fish intake and cardiovascular disease (CVD) risk using recent prospective studies. A systematic review and meta-analysis following the PRISMA guideline was conducted based on a random effects synthesis of multivariable-adjusted relative risks (RRs) of high vs. low categories of fish intake in relation to CVD incidence and mortality. Non-linear meta-regression was applied to investigate the shape of the association between fish intake and CVD risk. Sensitivity analysis and stratifications by type of CVD outcome, type of fish intake and type of cooking were performed. Based on 18 papers reporting 17 independent estimates of CVD risk (1,442,407 participants and 78,805 fatal and non-fatal CVD events), high vs. low intake of fish corresponded to about 8% reduced CVD risk (RR = 0.93 [0.88-0.98]). According to a non-linear dose-response meta-regression, 50 g of fish intake per day corresponded to a statistically significant 9% reduced fatal and non-fatal CVD risk (RR = 0.92 [0.90-0.95]). Similarly, fish intake in the range of a weekly intake of two to three portions of fish with a size of 150 g resulted in 8% fatal and non-fatal CVD risk reduction (RR = 0.93 [0.91-0.96]). The recommended two portions of fish a week reduces the risk of CVD outcomes by approximately 10%. A full portion of fish a day reduces CVD risk by up to 30%.

Corrigendum: Definition of the immune parameters related to COVID-19 severity.

[This corrects the article DOI: 10.3389/fimmu.2022.850846.].

C-reactive protein and clinical outcome in COVID-19 patients: the importance of harmonized measurements.

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.

The laboratory investigation of pleural fluids: An update based on the available evidence.

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.

Personalized prediction of optimal water intake in adult population by blended use of machine learning and clinical data.

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.

Pursuing appropriateness of laboratory tests: a 15-year experience in an academic medical institution.

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.

Inverse Association between Canned Fish Consumption and Colorectal Cancer Risk: Analysis of Two Large Case-Control Studies.

Fish is among the foods exerting favourable effects on colorectal cancer (CRC), but the possible role of canned fish has been insufficiently investigated. We aimed to investigate the relationship between canned fish consumption and CRC risk. We analysed data from two case−control studies conducted between 1992 and 2010 in several Italian areas, comprising a total of 2419 incident cases and 4723 hospital controls. Canned fish consumption was analysed according to the weekly frequency of consumption as <1 serving per week (s/w) (reference category), 1 < 2 s/w, and ≥2 s/w. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression models, adjusting for several recognised confounding factors. Overall, canned fish consumption was lower among cases than among controls (23.8% vs. 28.6%). An inverse association was found between canned fish consumption and CRC risk with a significant trend in risk (OR = 0.81, 95% CI: 0.71−0.92 for intermediate consumption and OR = 0.66, 95% CI: 0.51−0.85 for the highest one), which was consistent across strata of several covariates. This study is the first to offer a basis of support for canned fish consumption as a component of a healthy diet, and it has relevant public health implications given the high ranking of CRC in incidence and mortality worldwide.

Definition of the Immune Parameters Related to COVID-19 Severity.

A relevant portion of patients with disease caused by the severe acute respiratory syndrome coronavirus 2 (COVID-19) experience negative outcome, and several laboratory tests have been proposed to predict disease severity. Among others, dramatic changes in peripheral blood cells have been described. We developed and validated a laboratory score solely based on blood cell parameters to predict survival in hospitalized COVID-19 patients. We retrospectively analyzed 1,619 blood cell count from 226 consecutively hospitalized COVID-19 patients to select parameters for inclusion in a laboratory score predicting severity of disease and survival. The score was derived from lymphocyte- and granulocyte-associated parameters and validated on a separate cohort of 140 consecutive COVID-19 patients. Using ROC curve analysis, a best cutoff for score of 30.6 was derived, which was associated to an overall 82.0% sensitivity (95% CI: 78-84) and 82.5% specificity (95% CI: 80-84) for detecting outcome. The scoring trend effectively separated survivor and non-survivor groups, starting 2 weeks before the end of the hospitalization period. Patients' score time points were also classified into mild, moderate, severe, and critical according to the symptomatic oxygen therapy administered. Fluctuations of the score should be recorded to highlight a favorable or unfortunate trend of the disease. The predictive score was found to reflect and anticipate the disease gravity, defined by the type of the oxygen support used, giving a proof of its clinical relevance. It offers a fast and reliable tool for supporting clinical decisions and, most important, triage in terms of not only prioritization but also allocation of limited medical resources, especially in the period when therapies are still symptomatic and many are under development. In fact, a prolonged and progressive increase of the score can suggest impaired chances of survival and/or an urgent need for intensive care unit admission.

Cardiac dysfunction in Multisystem Inflammatory Syndrome in Children: An Italian single-center study.

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.

A step towards optimal efficiency of HbA1c measurement as a first-line laboratory test: the TOP-HOLE (Towards OPtimal glycoHemOgLobin tEsting) project.

OBJECTIVES: The TOP-HOLE (Towards OPtimal glycoHemOgLobin tEsting) project aimed to validate the HbA1c enzymatic method on the Abbott Alinity c platform and to implement the HbA1c testing process on the total laboratory automation (TLA) system of our institution. METHODS: Three different measuring systems were employed: Architect c4000 stand-alone (s-a), Alinity c s-a, and Alinity c TLA. Eight frozen whole blood samples, IFCC value-assigned, were used for checking trueness. A comparison study testing transferability of HbA1c results from Architect to Alinity was also performed. The alignment of Alinity TLA vs. s-a was verified and the measurement uncertainty (MU) estimated according to ISO 20914:2019. Turnaround time (TAT) and full time equivalent (FTE) were used as efficiency indicators. RESULTS: For HbA1c concentrations covering cut-offs adopted in clinical setting, the bias for both Architect and Alinity s-a was negligible. When compared with Architect, Alinity showed a mean positive bias of 0.54 mmol/mol, corresponding to a mean difference of 0.87%. A perfect alignment of Alinity TLA to the Alinity s-a was shown, and a MU of 1.58% was obtained, widely fulfilling the desirable 3.0% goal. After the full automation of HbA1c testing, 90% of results were released with a maximum TAT of 1 h, 0.30 FTE resource was also saved. CONCLUSIONS: The traceability of Alinity HbA1c enzymatic assay to the IFCC reference system was correctly implemented. We successfully completed the integration of the HbA1c testing on our TLA system, without worsening the optimal analytical performance. The shift of HbA1c testing from s-a mode to TLA significantly decreased TAT.

Lipase elevation in serum of COVID-19 patients: frequency, extent of increase and clinical value.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Investigation of possible underlying mechanisms behind water-induced glucose reduction in adults with high copeptin.

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.

Sources and clinical significance of aspartate aminotransferase increases in COVID-19.

BACKGROUND: Aspartate aminotransferase (AST) is often increased in COVID-19 and, in some studies, AST abnormalities were associated with mortality risk. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Impact of managing affected results in haemolysed samples of an infant-maternity hospital using an unconventional approach.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Associations between urinary hydration markers and metabolic dysfunction: a cross-sectional analysis of NHANES data, 2008-2010.

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.

The effect of Omega-3 polyunsaturated fatty acid supplementation on exercise-induced muscle damage.

BACKGROUND: Exercise-induced muscle damage (EIMD) results in transient muscle inflammation, strength loss, muscle soreness and may cause subsequent exercise avoidance. Omega-3 (n-3) supplementation may minimise EIMD via its anti-inflammatory properties, however, its efficacy remains unclear. METHODS: Healthy males (n = 14, 25.07 ± 4.05 years) were randomised to 3 g/day n-3 supplementation (N-3, n = 7) or placebo (PLA, n = 7). Following 4 weeks supplementation, a downhill running protocol (60 min, 65% V̇O2max, - 10% gradient) was performed. Creatine kinase (CK), interleukin (IL)-6 and tumour necrosis factor (TNF)-α, perceived muscle soreness, maximal voluntary isometric contraction (MVIC) and peak power were quantified pre, post, and 24, 48 and 72 h post-EIMD. RESULTS: Muscle soreness was significantly lower in N-3 vs PLA group at 24 h post-EIMD (p = 0.034). IL-6 was increased in PLA (p = 0.009) but not in N-3 (p = 0.434) following EIMD, however, no significant differences were noted between groups. Peak power was significantly suppressed in PLA relative to pre-EIMD but not in N-3 group at 24 h post-EIMD. However, no significant difference in peak power output was observed between groups. MVIC, CK and TNF-α were altered by EIMD but did not differ between groups. CONCLUSION: N-3 supplementation for 4 weeks may successfully attenuate minor aspects of EIMD. Whilst not improving performance, these findings may have relevance to soreness-associated exercise avoidance.