Effect of Plasma Unit Weight and Donor Sex on Post-Donation Citrate Level: An Experimental Study on Plasmapheresis Donors.

Introduction: Plasmapheresis donation is considered safe and well tolerated, although long-term effects need to be clarified. The volumes of anticoagulant (ACD-A) used are variable and depend primarily on hematocrit (HCT), total blood processed, amount of plasma collected, and donor characteristics. To elucidate the effect of the plasma unit weight setting on plasmapheresis efficiency and ACD-A distribution, we enrolled male donors undergoing a controlled apheresis process donating 700 g and 720 g in two different sessions. In parallel, we investigated a possible effect of sex, recruiting women donating 700 g of plasma. Methods: The study was conducted on men donating 720 g and (12 months later) 700 g of plasma, and on women donating 700 g of plasma. The main outcomes were pre-/post-donation delta (Δ) citrate concentration in donor plasma and ACD-A reinfused to the donor. Information concerning the annual check-up and the procedure was also collected. Intergroup comparisons (men donating 720 g vs. men donating 700 g and men vs. women both donating 700 g) and intragroup associations with donor and procedural characteristics were reported. Results: With the procedure set at 720 g, the machine processed around 44 mL more whole blood to collect 20 g more plasma, and 720 g donors received around 12 mL more anticoagulant than 700 g donors. Accordingly, Δ citrate concentration was 1.5 times higher (12 µm), with a greater variability observed for 720 g donations. Citrate concentration in the plasma unit was lower in the 720 g group, although not significantly. Comparing outcomes between women and men donating 700 g, we observed higher (and highly variable) Δ citrate and reinfused ACD-A in women, accompanied by lower anticoagulant levels in the unit. Increased Δ citrate is inversely associated with HCT and age in men and with HCT and triglycerides in women. Reinfused ACD-A correlates with HCT in women but not in men. Conclusion: Unit weight setting and sex influence an ACD-A shift from the estimated values toward an increased reinfusion to donor. In parallel, we observed an impact of age and sex on post-donation citrate metabolism. Altogether, these elements should be taken into account for the development of tailored approaches aimed at maintaining similar safety profiles for all donors using different plasmapheresis settings.

Functional Characterization of p.(Arg160Gln) PCSK9 Variant Accidentally Found in a Hypercholesterolemic Subject.

Familial hypercholesterolaemia (FH) is an autosomal dominant dyslipidaemia, characterised by elevated LDL cholesterol (LDL-C) levels in the blood. Three main genes are involved in FH diagnosis: LDL receptor (LDLr), Apolipoprotein B (APOB) and Protein convertase subtilisin/kexin type 9 (PCSK9) with genetic mutations that led to reduced plasma LDL-C clearance. To date, several PCSK9 gain-of-function (GOF) variants causing FH have been described based on their increased ability to degrade LDLr. On the other hand, mutations that reduce the activity of PCSK9 on LDLr degradation have been described as loss-of-function (LOF) variants. It is therefore important to functionally characterise PCSK9 variants in order to support the genetic diagnosis of FH. The aim of this work is to functionally characterise the p.(Arg160Gln) PCSK9 variant found in a subject suspected to have FH. Different techniques have been combined to determine efficiency of the autocatalytic cleavage, protein expression, effect of the variant on LDLr activity and affinity of the PCSK9 variant for the LDLr. Expression and processing of the p.(Arg160Gln) variant had a result similar to that of WT PCSK9. The effect of p.(Arg160Gln) PCSK9 on LDLr activity is lower than WT PCSK9, with higher values of LDL internalisation (13%) and p.(Arg160Gln) PCSK9 affinity for the LDLr is lower than WT, EC50 8.6 ± 0.8 and 25.9 ± 0.7, respectively. The p.(Arg160Gln) PCSK9 variant is a LOF PCSK9 whose loss of activity is caused by a displacement of the PCSK9 P' helix, which reduces the stability of the LDLr-PCSK9 complex.

Modifications of Chest CT Body Composition Parameters at Three and Six Months after Severe COVID-19 Pneumonia: A Retrospective Cohort Study.

We aimed to describe body composition changes up to 6-7 months after severe COVID-19 and to evaluate their association with COVID-19 inflammatory burden, described by the integral of the C-reactive protein (CRP) curve. The pectoral muscle area (PMA) and density (PMD), liver-to-spleen (L/S) ratio, and total, visceral, and intermuscular adipose tissue areas (TAT, VAT, and IMAT) were measured at baseline (T0), 2-3 months (T1), and 6-7 months (T2) follow-up CT scans of severe COVID-19 pneumonia survivors. Among the 208 included patients (mean age 65.6 ± 11 years, 31.3% females), decreases in PMA [mean (95%CI) -1.11 (-1.72; -0.51) cm2] and in body fat areas were observed [-3.13 (-10.79; +4.52) cm2 for TAT], larger from T0 to T1 than from T1 to T2. PMD increased only from T1 to T2 [+3.07 (+2.08; +4.06) HU]. Mean decreases were more evident for VAT [-3.55 (-4.94; -2.17) cm2] and steatosis [L/S ratio increase +0.17 (+0.13; +0.20)] than for TAT. In multivariable models adjusted by age, sex, and baseline TAT, increasing the CRP interval was associated with greater PMA reductions, smaller PMD increases, and greater VAT and steatosis decreases, but it was not associated with TAT decreases. In conclusion, muscle loss and fat loss (more apparent in visceral compartments) continue until 6-7 months after COVID-19. The inflammatory burden is associated with skeletal muscle loss and visceral/liver fat loss.

Performance evaluation of the high sensitive troponin I assay on the Atellica IM analyser.

Introduction: The Fourth Universal Definition of Myocardial Infarction Global Taskforce recommends the use of high sensitive troponin (hs-Tn) assays in the diagnosis of acute myocardial infarction. We evaluated the analytical performance of the Atellica IM High-sensitivity Troponin I Assay (hs-TnI) (Siemens Healthcare Diagnostics Inc., Tarrytown, USA) and compared its performance to other hs-TnI assays (Siemens Advia Centaur, Dimension Vista, Dimension EXL, and Abbott Architect (Wiesbaden, Germany)) at one or more sites across Europe. Materials and methods: Precision, detection limit, linearity, method comparison, and interference studies were performed according to Clinical and Laboratory Standards Institute protocols. Values in 40 healthy individuals were compared to the manufacturer's cut-offs. Sample turnaround time (TAT) was examined. Results: Imprecision repeatability CVs were 1.1-4.7% and within-lab imprecision were 1.8-7.6% (10.0-25,000 ng/L). The limit of blank (LoB), detection (LoD), and quantitation (LoQ) aligned with the manufacturer's values of 0.5 ng/L, 1.6 ng/L, and 2.5 ng/L, respectively. Passing-Bablok regression demonstrated good correlations between Atellica IM analyser with other systems; some minor deviations were observed. All results in healthy volunteers fell below the 99th percentile URL, and greater than 50% of each sex demonstrated values above the LoD. No interference was observed for biotin (≤ 1500 µg/L), but a slight bias at 5.0 g/L haemoglobin and 50 ng/L Tn was observed. TAT from was fast (mean time = 10.9 minutes) and reproducible (6%CV). Conclusions: Real-world analytical and TAT performance of the hs-TnI assay on the Atellica IM analyser make this assay fit for routine use in clinical laboratories.

Inflammatory burden and persistent CT lung abnormalities in COVID-19 patients.

Inflammatory burden is associated with COVID-19 severity and outcomes. Residual computed tomography (CT) lung abnormalities have been reported after COVID-19. The aim was to evaluate the association between inflammatory burden during COVID-19 and residual lung CT abnormalities collected on follow-up CT scans performed 2-3 and 6-7 months after COVID-19, in severe COVID-19 pneumonia survivors. C-reactive protein (CRP) curves describing inflammatory burden during the clinical course were built, and CRP peaks, velocities of increase, and integrals were calculated. Other putative determinants were age, sex, mechanical ventilation, lowest PaO2/FiO2 ratio, D-dimer peak, and length of hospital stay (LOS). Of the 259 included patients (median age 65 years; 30.5% females), 202 (78%) and 100 (38.6%) had residual, predominantly non-fibrotic, abnormalities at 2-3 and 6-7 months, respectively. In age- and sex-adjusted models, best CRP predictors for residual abnormalities were CRP peak (odds ratio [OR] for one standard deviation [SD] increase = 1.79; 95% confidence interval [CI] = 1.23-2.62) at 2-3 months and CRP integral (OR for one SD increase = 2.24; 95%CI = 1.53-3.28) at 6-7 months. Hence, inflammation is associated with short- and medium-term lung damage in COVID-19. Other severity measures, including mechanical ventilation and LOS, but not D-dimer, were mediators of the relationship between CRP and residual abnormalities.

Search for familial hypercholesterolemia patients in an Italian community: A real-life retrospective study.

BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is a common inherited disorder of low-density lipoprotein (LDL) catabolism that causes elevated LDL-cholesterol (LDL-C) and premature atherosclerotic cardiovascular disease (ASCVD). Despite the availability of effective treatments, FH remains underdiagnosed and undertreated. The aims of the study were to identify putative FH subjects using data from laboratory and cardiology databases, genetically characterize suspected FH patients referred to the Lipid Clinic and monitor attainment of treatment goals in identified patients. METHODS AND RESULTS: We retrieved the electronic health records of 221,644 individuals referred to laboratory for routine assessment and of 583 ASCVD patients (age ≤65) who underwent percutaneous transluminal coronary angioplasty (PTCA). We monitored the lipid profiles of subjects with LDL-C ≥ 250 mg/dl identified by laboratory survey (LS-P), PTCA patients and patients from the Lipid Clinic (LC-P). The laboratory survey identified 1.46% of subjects with LDL-C ≥ 190 mg/dl and 0.08% with LDL-C ≥ 250 mg/dl. Probable/definite FH was suspected in 3% of PTCA patients. Molecularly-confirmed FH was found in 44% of LC-P subjects. Five new LDLR mutations were identified. The 50% LDL-C reduction target was achieved by 70.6% of LC-P patients. Only 18.5% of PTCA patients reached the LDL-C < 55 mg/dl target. CONCLUSION: By using a combined approach based on laboratory lipid profiles, documented ASCVD and Lipid Clinic data, we were able to identify subjects with a high probability of being FH. Attainment of LDL-C goals was largely suboptimal. Efforts are needed to improve FH detection and achievement of lipid targets.

Four cases of acquired hemophilia A following immunization with mRNA BNT162b2 SARS-CoV-2 vaccine.

Acquired hemophilia A (AHA) is a rare autoimmune disease caused by neutralizing autoantibodies against coagulation Factor VIII. Immunomodulatory effects of SARS-CoV-2 vaccination are still poorly understood, with reports of immune-mediated conditions developing after immunization. In the province of Reggio Emilia, Northern Italy, we observed four cases of AHA following SARS-CoV-2 immunization with mRNA BNT162b2 vaccine (produced by Pfizer-BioNTech) during the first eight months from the beginning of SARS-CoV-2 vaccination campaign. During this time frame, 235,597 people received at least one dose of BNT162b2 vaccine. The total population of Reggio Emilia province is 526,349. The unusual observation of four cases of AHA in our province could be of interest and could sensitize healthcare personnel toward a possible complication of SARS-Cov-2 immunization. Nonetheless, vaccination benefits exceed potential side effects and play a central role in individual and public health to effectively protect people from COVID-19 and to stop the pandemic.

Comparison of Two Alternative Procedures to Obtain Packed Red Blood Cells for ß-Thalassemia Major Transfusion Therapy.

ß-thalassemia major (ßTM) patients require frequent blood transfusions, with consequences that span from allogenic reactions to iron overload. To minimize these effects, ßTM patients periodically receive leucodepleted packed red blood cells (P-RBCs) stored for maximum 14 days. The aim of this study was to compare two alternative routine procedures to prepare the optimal P-RBCs product, in order to identify differences in their content that may somehow affect patients' health and quality of life (QoL). In method 1, blood was leucodepleted and then separated to obtain P-RBCs, while in method 2 blood was separated and leucodepleted after removal of plasma and buffycoat. Forty blood donors were enrolled in two independent centers; couples of phenotypically matched whole blood units were pooled, divided in two identical bags and processed in parallel following the two methods. Biochemical properties, electrolytes and metabolic composition were tested after 2, 7 and 14 days of storage. Units prepared with both methods were confirmed to have all the requirements necessary for ßTM transfusion therapy. Nevertheless, RBCs count and Hb content were found to be higher in method-1, while P-RBCs obtained with method 2 contained less K+, iron and storage lesions markers. Based on these results, both methods should be tested in a clinical perspective study to determine a possible reduction of transfusion-related complications, improving the QoL of ßTM patients, which often need transfusions for the entire lifespan.

The value of computed tomography in assessing the risk of death in COVID-19 patients presenting to the emergency room.

OBJECTIVE: The aims of this study were to develop a multiparametric prognostic model for death in COVID-19 patients and to assess the incremental value of CT disease extension over clinical parameters. METHODS: Consecutive patients who presented to all five of the emergency rooms of the Reggio Emilia province between February 27 and March 23, 2020, for suspected COVID-19, underwent chest CT, and had a positive swab within 10 days were included in this retrospective study. Age, sex, comorbidities, days from symptom onset, and laboratory data were retrieved from institutional information systems. CT disease extension was visually graded as < 20%, 20-39%, 40-59%, or ≥ 60%. The association between clinical and CT variables with death was estimated with univariable and multivariable Cox proportional hazards models; model performance was assessed using k-fold cross-validation for the area under the ROC curve (cvAUC). RESULTS: Of the 866 included patients (median age 59.8, women 39.2%), 93 (10.74%) died. Clinical variables significantly associated with death in multivariable model were age, male sex, HDL cholesterol, dementia, heart failure, vascular diseases, time from symptom onset, neutrophils, LDH, and oxygen saturation level. CT disease extension was also independently associated with death (HR = 7.56, 95% CI = 3.49; 16.38 for ≥ 60% extension). cvAUCs were 0.927 (bootstrap bias-corrected 95% CI = 0.899-0.947) for the clinical model and 0.936 (bootstrap bias-corrected 95% CI = 0.912-0.953) when adding CT extension. CONCLUSIONS: A prognostic model based on clinical variables is highly accurate in predicting death in COVID-19 patients. Adding CT disease extension to the model scarcely improves its accuracy. KEY POINTS: • Early identification of COVID-19 patients at higher risk of disease progression and death is crucial; the role of CT scan in defining prognosis is unclear. • A clinical model based on age, sex, comorbidities, days from symptom onset, and laboratory results was highly accurate in predicting death in COVID-19 patients presenting to the emergency room. • Disease extension assessed with CT was independently associated with death when added to the model but did not produce a valuable increase in accuracy.

The impact of chest CT body composition parameters on clinical outcomes in COVID-19 patients.

We assessed the impact of chest CT body composition parameters on outcomes and disease severity at hospital presentation of COVID-19 patients, focusing also on the possible mediation of body composition in the relationship between age and death in these patients. Chest CT scans performed at hospital presentation by consecutive COVID-19 patients (02/27/2020-03/13/2020) were retrospectively reviewed to obtain pectoralis muscle density and total, visceral, and intermuscular adipose tissue areas (TAT, VAT, IMAT) at the level of T7-T8 vertebrae. Primary outcomes were: hospitalization, mechanical ventilation (MV) and/or death, death alone. Secondary outcomes were: C-reactive protein (CRP), oxygen saturation (SO2), CT disease extension at hospital presentation. The mediation of body composition in the effect of age on death was explored. Of the 318 patients included in the study (median age 65.7 years, females 37.7%), 205 (64.5%) were hospitalized, 68 (21.4%) needed MV, and 58 (18.2%) died. Increased muscle density was a protective factor while increased TAT, VAT, and IMAT were risk factors for hospitalization and MV/death. All these parameters except TAT had borderline effects on death alone. All parameters were associated with SO2 and extension of lung parenchymal involvement at CT; VAT was associated with CRP. Approximately 3% of the effect of age on death was mediated by decreased muscle density. In conclusion, low muscle quality and ectopic fat accumulation were associated with COVID-19 outcomes, VAT was associated with baseline inflammation. Low muscle quality partly mediated the effect of age on mortality.

The association between clinical laboratory data and chest CT findings explains disease severity in a large Italian cohort of COVID-19 patients.

BACKGROUND: Laboratory data and computed tomography (CT) have been used during the COVID-19 pandemic, mainly to determine patient prognosis and guide clinical management. The aim of this study was to evaluate the association between CT findings and laboratory data in a cohort of COVID-19 patients. METHODS: This was an observational cross-sectional study including consecutive patients presenting to the Reggio Emilia (Italy) province emergency rooms for suspected COVID-19 for one month during the outbreak peak, who underwent chest CT scan and laboratory testing at presentation and resulted positive for SARS-CoV-2. RESULTS: Included were 866 patients. Total leukocytes, neutrophils, C-reactive protein (CRP), creatinine, AST, ALT and LDH increase with worsening parenchymal involvement; an increase in platelets was appreciable with the highest burden of lung involvement. A decrease in lymphocyte counts paralleled worsening parenchymal extension, along with reduced arterial oxygen partial pressure and saturation. After correcting for parenchymal extension, ground-glass opacities were associated with reduced platelets and increased procalcitonin, consolidation with increased CRP and reduced oxygen saturation. CONCLUSIONS: Pulmonary lesions induced by SARS-CoV-2 infection were associated with raised inflammatory response, impaired gas exchange and end-organ damage. These data suggest that lung lesions probably exert a central role in COVID-19 pathogenesis and clinical presentation.

Pregnancy-related reference intervals for serum thyrotropin based on real-life clinical data.

AIM: During pregnancy, thyroid homeostasis is physiologically modified, leading to altered levels of thyrotropin (TSH): hence, the adoption of pregnancy-related, population- and method-specific reference ranges is recommended. This monocentric and retrospective study was conducted to establish local pregnancy-related reference intervals for serum TSH in singleton pregnant women using real-life clinical data. METHODS: We included women who measured serum TSH during pregnancy at our Laboratory over six years, excluding pregnant women with current or past history of thyroid disease, pituitary or autoimmune diseases, use of medications known to influence thyroid function, multiple and/or pathological pregnancies, BMI >30 Kg/m2. RESULTS: We retrieved a total of 3744 TSH results. Reference limits (90% confidence intervals) for TSH (in mIU/L) are: first trimester 0.09 (0.06-0.12) - 3.16 (3.05-3.29); second trimester 0.25 (0.11-0.30) - 3.55 (3.34-3.73); third trimester 0.42 (0.15-0.48) - 3.93 (3.80-4.08). CONCLUSION: In conclusion, real-life clinical data could be used to establish or verify local reference intervals for TSH in pregnant women: this may reduce the risk of misclassification of pregnant women undergoing thyroid function testing.

Accuracy of CT in a cohort of symptomatic patients with suspected COVID-19 pneumonia during the outbreak peak in Italy.

OBJECTIVE: To assess sensitivity/specificity of CT vs RT-PCR for the diagnosis of COVID-19 pneumonia in a prospective Italian cohort of symptomatic patients during the outbreak peak. METHODS: In this cross-sectional study, we included all consecutive patients who presented to the ER between March 13 and 23 for suspected COVID-19 and underwent CT and RT-PCR within 3 days. Using a structured report, radiologists prospectively classified CTs in highly suggestive, suggestive, and non-suggestive of COVID-19 pneumonia. Ground-glass, consolidation, and visual extension of parenchymal changes were collected. Three different RT-PCR-based reference standard definitions were used. Oxygen saturation level, CRP, LDH, and blood cell counts were collected and compared between CT/RT-PCR classes. RESULTS: The study included 696 patients (41.4% women; age 59 ± 15.8 years): 423/454 (93%) patients with highly suggestive CT, 97/127 (76%) with suggestive CT, and 31/115 (27%) with non-suggestive CT had positive RT-PCR. CT sensitivity ranged from 73 to 77% and from 90 to 94% for high and low positivity threshold, respectively. Specificity ranged from 79 to 84% for high positivity threshold and was about 58% for low positivity threshold. PPV remained ≥ 90% in all cases. Ground-glass was more frequent in patients with positive RT-PCR in all CT classes. Blood tests were significantly associated with RT-PCR and CT classes. Leukocytes, lymphocytes, neutrophils, and platelets decreased, CRP and LDH increased from non-suggestive to suggestive CT classes. CONCLUSIONS: During the outbreak peak (in a high-prevalence setting), CT presented high PPV and may be considered a good reference to recognize COVID-19 patients while waiting for RT-PCR confirmation. KEY POINTS: • During the epidemic peak, CT showed high positive predictive value and sensitivity for COVID-19 pneumonia when compared with RT-PCR. • Blood tests were significantly associated with RT-PCR and CT classes.

Serum Copeptin levels in the emergency department predict major clinical outcomes in adult trauma patients.

BACKGROUND: Early prognostication in trauma patients is challenging, but particularly important. We wanted to explore the ability of copeptin, the C-terminal fragment of arginine vasopressin, to identify major trauma, defined as Injury Severity Score (ISS) > 15, in a heterogeneous cohort of trauma patients and to compare its performances with lactate. We also evaluated copeptin performance in predicting other clinical outcomes: mortality, hospital admission, blood transfusion, emergency surgery, and Intensive Care Unit (ICU) admission. METHODS: This single center, pragmatic, prospective observational study was conducted at Arcispedale Santa Maria Nuova, a level II trauma center in Reggio Emilia, Italy. Copeptin determination was obtained on Emergency Department (ED) arrival, together with venous lactate. Different outcomes were measured including ISS, Revised Trauma Score (RTS), hospital and ICU admission, blood transfusion, emergency surgery, and mortality. RESULTS: One hundred and twenty five adult trauma patients admitted to the ED between June 2017 and March 2018. Copeptin showed a good ability to identify patients with ISS > 15 (AUC 0.819). Similar good performances were recorded also in predicting other outcomes. Copeptin was significantly superior to lactate in identifying patients with ISS > 15 (P 0.0015), and in predicting hospital admission (P 0.0002) and blood transfusion (P 0.016). Comparable results were observed in a subgroup of patients with RTS 7.84. CONCLUSIONS: In a heterogeneous group of trauma patients, a single copeptin determination at the time of ED admission proved to be an accurate biomarker, statistically superior to lactate for the identification of major trauma, hospital admission, and blood transfusion, while no statistical difference was observed for ICU admission and emergency surgery. These results, if confirmed, may support a role for copeptin during early management of trauma patients.

Heparin-induced lipoprotein precipitation apheresis in dyslipidemic patients: A multiparametric assessment.

Low-density lipoprotein (LDL) apheresis (LA) selectively eliminates lipoproteins containing apolipoprotein B 100 (ApoB100) on patients affected by severe dyslipidemia. In addition to lowering lipids, LA is thought to exert pleiotropic effects altering a number of other compounds associated with atherosclerosis, such as pro- and anti-inflammatory cytokines or pro-thrombotic factors. More knowledge needs to be gathered on the effects of LA, and particularly on its ability to modify blood components other than lipids. We performed a multiparametric assessment of the inflammatory, metabolic and proteomic profile changes after Heparin-induced lipoprotein precipitation (H.E.L.P.) apheresis on serum samples from nine dyslipidemic patients evaluating cholesterol and lipoproteins, plasma viscosity and density, metabolites, cytokines, PCSK9 levels and other proteins selectively removed after the treatment. Our results show that H.E.L.P. apheresis is effective in lowering lipoprotein and PCSK9 levels. Although not significantly, complement and inflammation-related proteins are also affected, indicating a possible transient epiphenomenon induced by the extracorporeal procedure.

Multi-site performance evaluation and Sigma metrics of 20 assays on the Atellica chemistry and immunoassay analyzers.

Background The Atellica Solution comprises chemistry (CH) and immunoassay (IM) analyzers. Recently, six early adopter clinical laboratories across Europe evaluated the analytical performance of 20 CH and IM assays. To measure analytical performance quality, Sigma metrics were calculated for individual-site and pooled-site results. Methods Precision, detection capability, linearity, and method comparison studies were performed according to Clinical Laboratory Standards Institute protocols. Global Sigma metrics across sites were calculated from pooled data at the medical decision level using total allowable error (TEa) goals from CLIA for CH assays, and TEa goals from RiliBÄK for IM assays; and, the equation: Sigma metrics=%TEa-%bias/%CV. A pooled %CV was calculated by combining the imprecision obtained from individual sites. Bias calculations were performed against the ADVIA Chemistry system or ADVIA Centaur system using Deming regression analysis (Passing-Bablok regression for electrolytes) on the pooled-site data. The 103 individual-site Sigma metric calculations used individual-site imprecision and pooled-bias. Results The limits of blank and detection results agreed with the manufacturer's claims. Most assays were linear across the assay range tested. Pooled Sigma metrics were good or better (>4 Sigma) for 18 of 20 assays; and, acceptable for urea nitrogen (3.1) and sodium (3.9), the latter values attributable to higher imprecision at one of five sites. Conclusions Sigma metrics for data generated across multiple real-world sites evaluating the Atellica Solution demonstrated good or better performance of greater than 4 Sigma for 18 of 20 assays tested. Overall, results verified the manufacturer's claims that methods were fit for use in clinical laboratories.