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Background: Antiretroviral drug combinations affect dolutegravir trough concentrations. Here, the authors focused on dolutegravir plus booster darunavir antiretroviral regimens to investigate the effect of the booster and/or timing of drug administration on dolutegravir and darunavir plasma trough concentrations., Methods: This retrospective observational study included consecutive people with HIV (PWH) receiving dolutegravir plus booster darunavir antiretroviral regimens for at least 3 months, with at least one assessment of dolutegravir and darunavir plasma trough concentrations., Results: A total of 200 drug therapeutic drug monitoring results from 116 PWH were included. Dolutegravir and darunavir trough concentrations ranged, respectively, from 70 to 3648 mcg/L and from 102 to 11,876 mcg/L. The antiretroviral drug combination associated with the highest dolutegravir trough concentration was dolutegravir plus darunavir/cobicistat, both once daily (1410 ± 788 mcg/L), whereas dolutegravir once daily plus darunavir/ritonavir twice daily had the lowest trough concentrations (686 ± 481 mcg/L). Doubling the dose of dolutegravir did not significantly increase drug trough concentrations compared with that of once-daily regimens. Instead, the highest darunavir trough concentrations were with ritonavir (2850 ± 1456 mcg/L, P < 0.05 versus cobicistat-based regimens). Doubling the drug dose resulted in a significant increase in the darunavir trough concentration (4445 ± 2926 mcg/L, P < 0.05)., Conclusions: Dolutegravir trough concentrations were significantly reduced in PWH receiving darunavir/ritonavir twice daily. This evidence should be carefully considered in clinical conditions requiring higher dolutegravir exposure, such as in the presence of drug-drug interactions with drugs known to reduce dolutegravir bioavailability or in highly experienced PWH., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Cognitive impairment is projected to affect a preponderant proportion of the aging population. Lifelong dietary habits have been hypothesized to play a role in preventing cognitive decline. Among the most studied dietary components, fish consumptionhas been extensively studied for its potential effects on the human brain., Aims: To perform a meta-analysis of observational studies exploring the association between fish intake and cognitive impairment/decline and all types of dementia., Methods: A systematic search of electronic databases was performed to identify observational studies providing quantitative data on fish consumption and outcomes of interest. Random effects models for meta-analyses using only extreme exposure categories, subgroup analyses, and dose-response analyses were performed to estimate cumulative risk ratios (RRs) and 95% confidence intervals (CIs)., Results: The meta-analysis comprised 35 studies. Individuals reporting the highest vs. the lowest fish consumption were associated with a lower likelihood of cognitive impairment/decline (RR = 0.82, 95% CI: 0.75, 0.90, I 2  = 61.1%), dementia (RR = 0.82, 95% CI: 0.73, 0.93, I 2  = 38.7%), and Alzheimer's disease (RR = 0.80, 95% CI: 0.67, 0.96, I 2  = 20.3%). The dose-response relation revealed a significantly decreased risk of cognitive impairment/decline and all cognitive outcomes across higher levels of fish intake up to 30% for 150 g/d (RR = 0.70, 95% CI: 0.52, 0.95). The results of this relation based on APOE ε4 allele status was mixed based on the outcome investigated., Conclusions: Current findings suggest fish consumption is associated with a lower risk of cognitive impairment/decline in a dose-response manner, while for dementia and Alzheimer's disease there is a need for further studies to improve the strength of evidence., (© 2024. The Author(s).)

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)., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

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%.

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.

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., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

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 (U Osm ) 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 U Osm . 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 U Osm . 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., (© 2022. The Author(s).)

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 B 12 , 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., (© 2022 the author(s), published by De Gruyter, Berlin/Boston.)

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.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Birindelli, Tarkowski, Gallucci, Schiuma, Covizzi, Lewkowicz, Aloisio, Falvella, Dolci, Riva, Galli and Panteghini.)

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., (© 2021. The Author(s).)

Objectives: The TOP-HOLE (Towards OPtimal glycoHemOgLobin tEsting) project aimed to validate the HbA 1c enzymatic method on the Abbott Alinity c platform and to implement the HbA 1c 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 HbA 1c 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 HbA 1c 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 HbA 1c 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 HbA 1c enzymatic assay to the IFCC reference system was correctly implemented. We successfully completed the integration of the HbA 1c testing on our TLA system, without worsening the optimal analytical performance. The shift of HbA 1c testing from s-a mode to TLA significantly decreased TAT., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

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., (© 2021. The Author(s).)

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 (U SG , 2007-2008 cohort) or urine osmolality (U Osm , 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 U SG but not U Osm 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 U SG but not U Osm 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 U SG  > 1.013 or U Osm  > 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, U SG remained positively associated with FPG (P < 0.01) and elevated FPG (P < 0.05)., Conclusion: These analyses provide population-based evidence that U SG as a proxy for hydration is associated with glucose homeostasis in NHANES 2007-2008. The same association was not significant when U Osm 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., (© 2021. The Author(s).)

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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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., (© 2021 Simone Caruso et al., published by De Gruyter, Berlin/Boston.)

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., (Copyright © 2021 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

It is unclear if mild-to-moderate dehydration independently affects mood without confounders like heat exposure or exercise. This study examined the acute effect of cellular dehydration on mood. Forty-nine adults (55 % female, age 39 (sd 8) years) were assigned to counterbalanced, crossover trials. Intracellular dehydration was induced with 2-h (0·1 ml/kg per min) 3 % hypertonic saline (HYPER) infusion or 0·9 % isotonic saline (ISO) as a control. Plasma osmolality increased in HYPER (pre 285 (sd 3), post 305 (sd 4) mmol/kg; P < 0·05) but remained unchanged in ISO (pre 285 (sd 3), post 288 (sd 3) mmol/kg; P > 0·05). Mood was assessed with the short version of the Profile of Mood States Questionnaire (POMS). The POMS sub-scale (confusion-bewilderment, depression-dejection, fatigue-inertia) increased in HYPER compared with ISO (P < 0·05). Total mood disturbance score (TMD) assessed by POMS increased from 10·3 (sd 0·9) to 16·6 (sd 1·7) in HYPER (P < 0·01), but not in ISO (P > 0·05). When TMD was stratified by sex, the increase in the HYPER trial was significant in females (P < 0·01) but not in males (P > 0·05). Following infusion, thirst and copeptin (surrogate for vasopressin) were also higher in females than in males (21·3 (sd 2·0), 14·1 (sd 1·4) pmol/l; P < 0·01) during HYPER. In conclusion, cellular dehydration acutely degraded specific aspects of mood mainly in women. The mechanisms underlying sex differences may be related to elevated thirst and vasopressin.

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.

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% V̇O 2 max, - 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.

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 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., (© 2020 College of American Pathologists.)

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.

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 U col ., 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 U col changed from > 4 to < 4 (+ 1435 ± 812 mL) than those whose U col 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.

Background: Epidemiological studies in humans show increased concentrations of copeptin, a surrogate marker of arginine vasopressin (AVP), to be associated with increased risk for type 2 diabetes., Objectives: To examine the acute and independent effect of osmotically stimulated AVP, measured via the surrogate marker copeptin, on glucose regulation in healthy adults., Methods: Sixty subjects (30 females) participated in this crossover design study. On 2 trial days, separated by ≥7 d (males) or 1 menstrual cycle (females), subjects were infused for 120 min with either 0.9% NaCl [isotonic (ISO)] or 3.0% NaCl [hypertonic (HYPER)]. Postinfusion, a 240-min oral-glucose-tolerance test (OGTT; 75 g) was administered., Results: During HYPER, plasma osmolality and copeptin increased (P < 0.05) and remained elevated during the entire 6-h protocol, whereas renin-angiotensin-aldosterone system hormones were within the lower normal physiological range at the beginning of the protocol and declined following infusion. Fasting plasma glucose did not differ between trials (P > 0.05) at baseline and during the 120 min of infusion. During the OGTT the incremental AUC for glucose from postinfusion baseline (positive integer) was greater during HYPER (401.5 ± 190.5 mmol/L·min) compared with the ISO trial (354.0 ± 205.8 mmol/L·min; P < 0.05). The positive integer of the AUC for insulin during OGTT did not differ between trials (HYPER 55,850 ± 36,488 pmol/L·min compared with ISO 57,205 ± 31,119 pmol/L·min). Baseline values of serum glucagon were not different between the 2 trials; however, the AUC of glucagon during the OGTT was also significantly greater in HYPER (19,303 ± 3939 ng/L·min) compared with the ISO trial (18,600 ± 3755 ng/L·min; P < 0.05)., Conclusions: The present data indicate that acute osmotic stimulation of copeptin induced greater hyperglycemic responses during the oral glucose challenge, possibly due to greater glucagon concentrations.This study was registered at clinicaltrials.gov as NCT02761434., (Copyright © American Society for Nutrition 2019.)

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.

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., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: Because elevated copeptin, a marker of vasopressin, is linked to low water intake and high diabetes risk, we tested the effect of water supplementation on copeptin and fasting glucose., Design, Setting, and Participants: Thirty-one healthy adults with high copeptin (>10.7 pmol · L-1 in men and >6.1 pmol·L-1 in women) identified in a population-based survey from 2013 to 2015 and with a current 24-hour urine osmolality of >600 mOsm · kg-1 were included., Intervention: Addition of 1.5 L water daily on top of habitual fluid intake for 6 weeks., Main Outcome Measure: Pre- and postintervention fasting plasma copeptin concentrations., Results: Reported mean water intake increased from 0.43 to 1.35 L · d-1 (P < 0.001), with no other observed changes in diet. Median (interquartile range) urine osmolality was reduced from 879 (705, 996) to 384 (319, 502) mOsm · kg-1 (P < 0.001); urine volume increased from 1.06 (0.90, 1.20) to 2.27 (1.52, 2.67) L · d-1 (P < 0.001); and baseline copeptin decreased from 12.9 (7.4, 21.9) pmol · L-1 to 7.8 (4.6;11.3) pmol · L-1 (P < 0.001). Water supplementation reduced fasting plasma glucose from a mean (SD) of 5.94 (0.44) to 5.74 (0.51) (P = 0.04). The water-associated reduction of both fasting copeptin and glucose concentration in plasma was most pronounced in participants in the top tertile of baseline copeptin., Conclusions: Water supplementation in persons with habitually low water consumption and high copeptin levels is effective in lowering copeptin. It appears a safe and promising intervention with the potential of lowering fasting plasma glucose and thus reducing diabetes risk. Further investigations are warranted to support these findings., (Copyright © 2019 Endocrine Society.)

The use of procalcitonin (PCT) as a tool to assist clinicians in using antibiotics in intensive care patients has been postulated. Here we evaluate the efficacy of procalcitonin determination in helping clinicians in the decision to start or discontinue an antibiotic treatment in patients admitted to infectious disease wards. A retrospective observational single centre study was conducted in two infectious disease wards. Descriptive and inferential statistical analysis was carried out and receiver operating characteristic curves and area under the curve (AUC) were used to assess the accuracy of PCT and C-reactive protein (CRP) in separating patients undergoing antibiotic treatment or otherwise. In all, 164 patients were analysed of whom 99 (60.4%) were not on antibiotic treatment at the time of PCT determination, whereas 65 (39.6%) took antibiotics. Regarding the accuracy of PCT and CRP in determining a subsequent antibiotic prescription in patients without an ongoing antibiotic treatment, no statistically significant difference between the two markers was detected [AUC, 0.75; confidence interval (CI) 95%: 0.66-0.84; vs 0.69; CI 95%: 0.59-0.79 for PCT and CRP, respectively; p=0.32]. Conversely, in patients with an ongoing antibiotic treatment a statistically significant difference between PCT and CRP AUC in their ability to determine an antibiotic interruption was observed [0.77 (CI 95%: 0.65-0.89) vs 0.59 (CI 95%: 0.45-0.73) (p=0.03)]. PCT determination appeared to be more helpful than CRP in determining discontinuation of an antibiotic treatment in non-intensive care patients. However, PCT should supplement and not supplant a careful clinical evaluation.

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.

Background: The morphological examination of urinary sediment (MEUS) is traditionally associated with urinalysis (UA), with workload implications and the need for automation of its execution., Methods: Considering MEUS as a test requiring specialized knowhow and skill for its execution, since 2005 in our laboratory it is performed for inpatients only upon specific request. Eleven years after, we have analyzed the long-term impact of this approach on the provided service. We evaluated results in the 2009-2016 period, in which our hospital did not undergo any change both in the number of beds and in the clinical case-mix., Results: From 2009 to 2013 an average of 2264 MEUS and 10,204 UA per year were ordered, respectively, with an average ratio of 22.2%. Since 2014, a change on computerized order entry involving MEUS caused a further decrease of its requests (in average, 923 per year), which was not associated to a decrease in UA (in average, 9810 per year) (in average, MEUS/UA 9.4%). MEUS requests came mainly from Paediatrics (47.8%), Nephrology (20.9%) and Rheumatology (18.3%) wards. By filling a satisfaction survey, clinical wards evaluated the provided service as satisfactory, while highlighting some critical issues, mainly referred to preanalytical phase., Conclusions: The alternative proposal for managing MEUS presented in this paper markedly reduces the number of requests and increases their appropriateness. This is achieved without any negative impact on patient care., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

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 ~1g/L of free hemoglobin). Monthly and cumulative CVs were calculated., Results: During 21months, 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., (Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

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.