Clinical Chemistry Tests Research Articles

Hematological and Chemical Profiles in a Porcine Model of Severe Multiple Trauma

Background: Clinical chemistry and hematological tests are widely used to monitor the clinical course of several diseases. However, these parameters are sparse in large-animal models of multiple trauma (MT). Thus, we aimed to provide these missing data to improve future experimental setups in trauma research. Methods: Male pigs (German Landrace pigs) were randomized into either an MT group (n = 8) including blunt thoracic trauma, tibial fracture, and controlled hemorrhage or a sham group (n = 8) without any trauma. After trauma induction, all animals received intensive care treatment for 72 h under anesthesia, including mechanical ventilation and volume resuscitation. Blood and urine samples were obtained to measure common hematological and chemical parameters before trauma (0 h), after trauma (1.5 h), during resuscitation (2.5 h), after fracture stabilization (3.5 h), and at 12, 24, 48, and 72 h. Statistical analyses were performed using a linear mixed model (group × time) and Welch’s ANOVA. Results: MT led to a perceptible immunological reaction. Between groups, significantly different time courses of leukocyte counts (p = 0.034) and lymphocyte proportions (p = 0.001) were observed. Moreover, MT changed the time course of total protein (p = 0.006). Significantly lower concentrations compared to sham were found in MT at each single time point starting at 1.5 h to the end of the observation period (all p < 0.05). Conclusions: Our results indicate that a traumatic insult leads to significant alterations in the immune system already shortly after trauma. Together with the additional catabolic reactions observed, these alterations might contribute to the occurrence of later complications. The presented data provide valid references for further experimental setups with prolonged observation times, especially in similar porcine models of MT.

Improved Sample Quality and Decreased Turnaround Time When Using Plasma Blood Collection Tubes with a Mechanical Separator in a Large University Hospital.

Serum is commonly used for clinical chemistry testing but many conditions can affect the clotting process, leading to poor sample quality and impaired workflow. With serum gel tubes, we found a high proportion of sample probe aspiration errors on our Beckman AU5800 analyzers. We decided to implement the BD Barricor™ plasma tubes, and we validated an off-specification centrifugation scheme and verified that results obtained for 65 chemistry and immunochemistry tests were comparable to those obtained in serum gel tubes. Finally, we evaluated the impact of this new tube on sample error rate and laboratory turnaround time. To validate centrifugation settings, 50 paired samples were collected in Barricor tubes and centrifuged at 1912 × g for 10 min or 5 min (off-specification). To compare serum gel tubes with Barricor plasma tubes, 119 paired samples were collected from volunteers and results were analyzed using weighed Deming regression. Finally, the proportion of aspiration errors and laboratory TAT for potassium were measured before and after implementing Barricor tubes. Barricor tubes showed clinically acceptable equivalence to serum gel tubes for the studied analytes, and the off-specification centrifugation scheme did not affect the results. Implementing Barricor tubes improved the laboratory workflow by decreasing the aspiration error rates (2.01% to 0.77%, P < 0.001) and lowering hemolysis (P < 0.001). The laboratory TAT for potassium were also significantly lowered (P < 0.001). Use of Barricor tubes instead of serum gel tubes leads to better sample quality, shorter more reproducible laboratory TAT, and decreases costs associated with error management.

High dose ascorbic acid treatment in COVID-19 patients raised some problems in clinical chemistry testing

Abstract Objective COVID-19 pandemia still continues to threaten the whole world. High dose ascorbic acid (AA) infusion is a choice of treatment and its efficiency is still being investigated. AA interferes with many clinical chemistry tests. However, data about the interference of high concentrations of AA is not sufficient. In this study, we aimed to investigate the interference of AA at high concentrations on commonly used chemistry assays. Materials and Methods Serum samples at AA concentrations of 200, 150, 100, 75, 50, 25, 10, 5, 2 and 0 mg/dL were prepared by using the stock solution of 15000 mg/dL AA. Each sample was analyzed by using the most common 30 chemistry tests (Abbott Architect C8000, Illinois, USA) and a POCT glucometer (STANDARD GlucoNavii, Gyeonggi-do, Republic of Korea). Results Creatinine, sodium and glucose (POCT) tests were found to be positively interfered by increasing AA concentrations; while direct bilirubin, lipase, UIBC, triglyceride, total cholesterol, HDL/LDL cholesterol tests were negatively interfered. Absolute interference (%) increased as the AA concentration increased. Conclusion This is the largest and first study to investigate the interference of high dose AA, which is used in severe COVID-19 patients nowadays. Manufacturers and clinicians should be aware of the possibility of aberrant results due to high dose AA infusion. Clinicians should not forget to consult a laboratory specialist, since he is the only person to monitor the reactions in all assays, and know the technical subjects like interferences, assay method specifications. This issue is very important for correct decision-making and interpretation of the data-mining studies accurately and efficiently.

Evaluation of Laboratory Performance, Associated Factors and Staff Awareness Towards Achieving Turnaround Time in Tertiary Hospitals, Ethiopia.

WHO recommends that each laboratory should establish turnaround time (TAT) to monitor and evaluate performance throughout processes. The status of established TAT was not yet assessed in Ethiopian Armed Force Comprehensive Specialized Hospital. The aim of this study was to evaluate the laboratory performance and associated factors towards achieving TAT in clinical chemistry and hematology tests at Armed Force Comprehensive Specialized Hospital, Addis Ababa, Ethiopia. Hospital-based cross-sectional study was conducted from April 2019 to June 2019. Standardized questionnaire was designed to collected data on awareness of laboratory staffs about TAT. The data was entered, cleaned and analyzed using SPSS version 24.0 Software. Logistic regression analysis was done to find out statistically significant association and strength of association between dependent and independent variables at pvalue <0.05. A total of 422 test results were systematically selected with 100% response rates. Of these, 253(59.9%) were chemistry tests. From the expected < 90min TAT clinical chemistry tests, only 41(16.2%) and from < 60min TAT time for hematology tests, 37(21.9%) met the target. The laboratory TAT was affected by factors including high work load, laboratory information system problem, power interruption and sample collection time. Moreover, the level of knowledge, attitude and practices of laboratory staffs towards laboratory TAT were 60%, 85.7% and 62.9% respectively. Overall achievement of clinical Chemistry and hematology tests TAT was poor. The finding might reflect other public hospital situation in Addis Ababa. Thus, additional large scale studies need to conduct.

Subacute Oral Toxicity Evaluation of Freeze-Dried Powder of Locusta migratoria.

Novel food sources have enormous potential as nutritional supplements. For instance, edible insects are considered as an alternative food source due to their higher protein content; moreover, they are economically efficient reproducers and have high in nutritional value. In this study, we investigated the toxicity of the freeze-dried powder of Locusta migratoria (fdLM), known to contain rich proteins as well as fatty acids. The objective of the present study was to evaluate the subacute toxicity of fdLM in male and female Sprague-Dawley (SD) rats. The SD rats were divided into four groups based on the dosage of fdLM administered: dosage of 0 (vehicle control), 750, 1,500, and 3,000 mg/kg/day were administered for 28 days. Toxicological assessments including observations on food consumption, body and organ weights, clinical signs, mortality, ophthalmologic tests, urinalyses, hematologic tests, clinical chemistry tests, gross findings, and histopathology tests were performed. Clinical signs, urinalyses, hematology, serum biochemistry tests, and organ weight examinations revealed no fdLM-related toxicity. The no-observed-adverse-effect level for fdLM was higher than 3,000 mg/kg/day in rats of both sexes; therefore, fdLM, in conclusion, can be considered safe as an edible alternative human and animal food source material.

Establishing hemolysis and lipemia acceptance thresholds for clinical chemistry tests

BackgroundA key component of laboratory medicine is the evaluation of specimen suitability for downstream analytical testing. Accurate identification and characterization of the impact of interferents on clinical chemistry analytes is important for patient care. To empirically assess the influence of hemolysis and lipemia on clinical chemistry tests analyzed on a Roche cobas® c701 system, we evaluated serum pools spiked with increasing concentrations of hemolysate and Intralipid®. MethodsUsing an interferent acceptance threshold of within ± 10% of the non-hemolyzed or non-lipemic results, 31 routine chemistry analytes were evaluated. ResultsThe majority of analytes were determined to have the same or very similar acceptability thresholds as those listed in the vendor package insert. However, several analytes resulted in new thresholds that deviated from manufacturer recommendations (9 higher and 2 lower for lipemia, 7 higher and 6 lower for hemolysis). Samples with high enzyme activities (LDH, ALT, AST, ALP, and CK) were observed to tolerate higher levels of hemolysis, and tiered hemolysis thresholds were established for these enzymes. Independent evaluation of indices is recommended to enable thoughtful implementation of specimen quality criteria and to provide guidance to laboratorians and providers on the nature of these interferences.

Alteration of Clinical Chemistry Parameters Among Visceral Leishmaniasis Patients in Western Tigrai, Ethiopia, 2018/2019: A Comparative Cross-Sectional Study.

BackgroundVisceral leishmaniasis causes alterations of lipid metabolism and it is associated with hypocholesterolemia and severe hypertriglyceridemia. Hepatic dysfunction and life-threatening hepatitis are associated with visceral leishmaniasis. Kidney damage is frequently associated with increased morbidity and mortality in visceral leishmaniasis patients.MethodsA cross-sectional study was carried out to assess the alterations of clinical chemistry parameters among visceral leishmaniasis patients attending Kahsay Abera and Mearg hospitals, Northwest Ethiopia. A total of 100 visceral leishmaniasis patients and 100 healthy controls without visceral leishmaniasis were selected by using convenient sampling techniques. Data were entered and analyzed using statistical package for social sciences (SPSS) version 23.ResultsResults were showed that the mean value of serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, and triglyceride was significantly higher in visceral leishmaniasis patients than in apparently healthy controls, but the mean value of serum urea and total cholesterol was significantly lower in visceral leishmaniasis patients than healthy controls.ConclusionThe finding of this study concluded that visceral leishmaniasis causes significant alterations of clinical chemistry tests like liver and lipid profile tests compared to healthy controls.

SARS-COV-2 can induce an alteration of the autoimmune profile

Objective: The study evaluated the autoimmune profile of COVID-19 positive hospitalised patients. Methods: 40 hospitalised patients with a confirmed diagnosis of COVID-19 were given clinical chemistry and autoimmunity tests. Results: The 40 patients enrolled in our hospital had elevated levels of common inflammatory markers such as C-Reactive Protein (CRP), Lactate Dehydrogenase (LDH) and ferritin. Interleukin-6 (IL-6) concentration was also increased, confirming the key role of this interleukin during severe acute respiratory syndrome (SARS-CoV-2) infection. The most common autoimmunity tests were performed. A significant prevalence of anti-nuclear antibodies (ANA), anti-neutrophil cytoplasmic antibodies (ANCA) and anti-Saccaromyces cerevisiae (ASCA IgA and IgG) was found. Patients showing a de novo autoantibody response were those with a worse disease prognosis. Conclusion: Our study shows that COVID-19 infection can trigger an autoimmune response and could induce the onset of autoimmune diseases. These data explain why drugs used to treat autoimmune diseases could also be useful in combating SARS-CoV-2 infection.

Safety and Vision Outcomes of Subretinal Gene Therapy Targeting Cone Photoreceptors in Achromatopsia

Achromatopsia linked to variations in the CNGA3 gene is associated with day blindness, poor visual acuity, photophobia, and involuntary eye movements owing to lack of cone photoreceptor function. No treatment is currently available. To assess safety and vision outcomes of supplemental gene therapy with adeno-associated virus (AAV) encoding CNGA3 (AAV8.CNGA3) in patients with CNGA3-linked achromatopsia. This open-label, exploratory nonrandomized controlled trial tested safety and vision outcomes of gene therapy vector AAV8.CNGA3 administered by subretinal injection at a single center. Nine patients (3 per dose group) with a clinical diagnosis of achromatopsia and confirmed biallelic disease-linked variants in CNGA3 were enrolled between November 5, 2015, and September 22, 2016. Data analysis was performed from June 6, 2017, to March 12, 2018. Patients received a single unilateral injection of 1.0 × 1010, 5.0 × 1010, or 1.0 × 1011 total vector genomes of AAV8.CNGA3 and were followed up for a period of 12 months (November 11, 2015, to October 10, 2017). Safety as the primary end point was assessed by clinical examination of ocular inflammation. Systemic safety was assessed by vital signs, routine clinical chemistry testing, and full and differential blood cell counts. Secondary outcomes were change in visual function from baseline in terms of spatial and temporal resolution and chromatic, luminance, and contrast sensitivity throughout a period of 12 months after treatment. Nine patients (mean [SD] age, 39.6 [11.9] years; age range, 24-59 years; 8 [89%] male) were included in the study. Baseline visual acuity letter score (approximate Snellen equivalent) ranged from 34 (20/200) to 49 (20/100), whereas baseline contrast sensitivity log scores ranged from 0.1 to 0.9. All 9 patients underwent surgery and subretinal injection of AAV8.CNGA3 without complications. No substantial safety problems were observed during the 12-month follow-up period. Despite the congenital deprivation of cone photoreceptor-mediated vision in achromatopsia, all 9 treated eyes demonstrated some level of improvement in secondary end points regarding cone function, including mean change in visual acuity of 2.9 letters (95% CI, 1.65-4.13; P = .006, 2-sided t test paired samples). Contrast sensitivity improved by a mean of 0.33 log (95% CI, 0.14-0.51 log; P = .003, 2-sided t test paired samples). Subretinal gene therapy with AAV8.CNGA3 was not associated with substantial safety problems and was associated with cone photoreceptor activation in adult patients, as reflected by visual acuity and contrast sensitivity gains. ClinicalTrials.gov Identifier: NCT02610582.

Clinical chemistry tests for patients with COVID-19 – important caveats for interpretation

Article Clinical chemistry tests for patients with COVID-19 – important caveats for interpretation was published on July 1, 2020 in the journal Clinical Chemistry and Laboratory Medicine (CCLM) (volume 58, issue 7).

Therapeutic effect of an anti-human-TNF-alpha antibody and itraconazole on feline infectious peritonitis.

Feline infectious peritonitis (FIP) is a fatal disease in wild and domestic cat species. Although several drugs are expected to be useful as treatments for FIP, no drugs are available in clinical practice. In this study, we evaluated the therapeutic effect of combined use of adalimumab (an anti-human-TNF-alpha monoclonal antibody, ADA) and itraconazole (ICZ), which are presently available to veterinarians. The neutralizing activity of ADA against fTNF-alpha-induced cytotoxicity was measured in WEHI-164 cells. Ten specific pathogen-free (SPF) cats were inoculated intraperitoneally with type I FIPV KU-2. To the cats that developed FIP, ADA (10 mg/animal) was administered twice between day 0 and day 4 after the start of treatment. ICZ (50 mg/head, SID) was orally administered daily from day 0 after the start of treatment. ADA demonstrated dose-dependent neutralizing activity against rfTNF-alpha. In an animal experiment, 2 of 3 cats showed improvements in FIP clinical symptoms and blood chemistry test results, an increase in the peripheral blood lymphocyte count, and a decrease in the plasma alpha 1-AGP level were observed after the beginning of treatment. One of the cats failed to respond to treatment and was euthanized, although the viral gene level in ascites temporarily decreased after the start of treatment. ADA was found to have neutralizing activity against rfTNF-alpha. The combined use of ADA and ICZ showed a therapeutic effect for experimentally induced FIP. We consider these drugs to be a treatment option until effective anti-FIPV drugs become available.

Review of interference indices in body fluid specimens submitted for clinical chemistry analyses

ObjectivesThe aims of this study were to retrospectively investigate interference indices in a wide range of body fluid specimens and compare these indices to those found in serum/plasma. Design and MethodsThis retrospective study evaluated interference indices for hemolysis, icterus, and lipemia in 2752 body fluid specimens submitted for clinical chemistry testing. ResultsThe distribution of interference indices for body fluid samples was generally similar to that of serum/plasma interference indices. Hemolysis of specimens submitted for lactate dehydrogenase (LD) represented the most common interference for body fluid chemistries. Body fluids collected from postsurgical drain sites had a higher proportion of tests exceeding both icterus and lipemic limits compared to serum/plasma specimens. ConclusionsOverall, degrees of hemolysis, icterus, and lipemia observed in body fluid specimens were in large part similar to serum/plasma specimens, with a few notable differences. Body fluids exhibited a higher proportion of samples with severe icterus or lipemia. Severely lipemic body fluid samples were significantly less likely to also be hemolyzed relative to severely lipemic serum/plasma specimens. LD was the test most commonly affected by interference across all body fluid types. False elevations in pleural fluid LD induced by hemolysis can lead to mis-classification of transudative effusions as exudative using Light’s criteria. The possible impact of interferences on clinical chemistry testing in body fluids is an important post-analytical consideration.

P252 Incidental finding of a chronic left ventricular pseudoaneurysm years after surgical aortic valve replacement

Abstract Case presentation A 35-years old female was referred to our outpatient clinic with unclear thoracic pain and dyspnea. Clinical chemistry testing was unremarkable. Electrocardiography (ECG) showed T-wave inversion in the anterior-lateral leads. Chest X-ray displayed an oval bulge on the left border of the heart. The physical exam revealed a systolic murmur on top of the closing click sound of a mechanical aortic valve prothesis which had been implanted nine years ago. Since that time, the patient had not had regular checkups and the actual consultation was motivated by her aggravating symptoms only. Findings. In transthoracic echocardiography, the mechanical aortic valve prothesis exhibited an acceptable peak velocity of 2.7 m/s with a mean gradient of 18 mm Hg and only mild paravalvular regurgitation. The native mitral and tricuspid valves were functionally and morphologically normal. Left and right ventricle were of normal systolic and diastolic function and normal size. No signs of pericardial effusion were detected. However, a big (40x22mm) saccular structure with a narrow (10 mm) neck was visible at the apex of the left ventricle, see left panel of figure. At the neck, a bidirectional flow between the saccular structure and the left ventricle was detected with a peak velocity of 2,5 m/sec indicating the presence of a pseudoaneurysm. Its linings were calcified and free of discernable thrombus formation, although the flow inside was turbulent as evidenced in the contrast echocardiogram, see right panel of figure. Subsequently, CT-imaging confirmed the diagnosis and surgical resection of the pseudoaneurysm was successfully performed 10 days later. The surgeon noted that the walls of the resected cavity contained thrombotic masses despite respective negative findings on CT and echo. The postoperative course was uneventful, and the patient was discharged in good condition with normal left and right ventricular function and no regional left ventricular wall abnormalities. A year later, she was however re-admitted with prosthetic aortic valve stenosis due to thrombus formation on one the leaflets in the second trimester of a pregnancy. Discussion This is an exceptional case of chronic left ventricular pseudoaneurysm following aortic valve replacement. Since the patient had no history of myocardial infarction or of other potential causes that could explain the formation of a pseudoaneurysm, it is likely to be a remnant of venting the left ventricle during the original surgical procedure. The patient had been unattended and asymptomatic for several years which allowed chronification as indicated by the calcifications of the inner linings. Still, immediate surgical repair was mandatory due to the high risk of rupture and thromboembolism. Abstract P252 Figure.

High Sensitivity Detection of Anti-DFS70 Antibodies by Radioimmunoprecipitation Assay (RIPA).

Autoantibodies against the chromosome associated protein DFS70/LEDGF (dense fine speckled 70/ lens epithelial growth factor; anti-DSF70) are increasingly being regarded as biomarkers for the diagnostic exclusion of systemic autoimmune rheumatic diseases (SARD). In routine ANA screening by indirect immunofluores-cence (IIFT) tests the presence of anti-DFS70 may first be presumed because of their characteristic immunofluo-rescence pattern (AC-2 pattern) and then be confirmed by antigen specific assays, a sequential approach, which may underestimate the prevalence of anti-DFS70 because of the inherent shortcomings of the ANA-IIFT. We therefore, for the first time, determined the prevalence of anti-DFS70 in patient sera by means of a sensitive and specific radioimmunoprecipitation assay (RIPA) as compared to a commercial ELISA. Blood specimens referred for routine ANA screening (n = 1.100, ANA-Series) or for basic clinical chemistry tests (n = 350, CC-Series) were assayed for the prevalence of anti-DFS70 by RIPA using 35S-methionine labelled full-length DFS70 (FL-DFS70) as well as a C-terminal DFS70 fragment (CT-DFS70) generated by in vitro transcription/translation (ivTT) of the respective cDNAs. ELISA was performed using an anti-DFS70 test-kit (Eu-roimmun) and ANA-IIFT by means of commercial HEp-2 cells (INOVA) and appropriately chessboard titrated conjugates (Dianova). Accessory SARD markers (anti-dsDNA, anti-ENA) were determined in sera positive for anti-DFS70. The detection of anti-DFS70 by RIPA was considerably more sensitive than by ELISA, resulting in an overall detection rate of 9.0% (ANA-Series) and 8.0% (CC-Series) compared to ELISA revealing 4.6% (ANA-Se-ries) and 2.6% (CC-Series) anti-DFS70 positive sera. Of 99 RIPA reactive sera (ANA-Series) 72% were reactive against anti-FL-DFS70, 93% against CT-DFS70, polyspecific antibodies coexisted in 65%, reacting with both antigen specificities, 28% showed monospecific reaction with CT-DFS70 and 7% monospecific with FL-DFS70, indicating also the possible existence of antibodies specific for N-terminal epitopes in DSF70. Similar frequencies were seen in sera of the CC-series. The RIPA measured antibody concentrations (Rratio) obtained with FL-DSF70 antigen and CT-DSF70 antigen showed a correlation. There was also a correlation between the IIFT-ANA titers and Rratio found by RIPA. The consensus of suspected AC-2 pattern in ANA-IIFT and anti-DFS70 measured by RIPA was about 80%. No significant correlation existed between the antibody concentrations measured by RIPA and ELISA. Additional SARD markers were present in 24% of anti-DFS70 positive sera referred for ANA screening. No additional markers were seen in sera of the CC-Series. RIPA constitutes a highly-sensitive assay for detection of anti-DFS70 in human sera. ANA-IIFT screening performed under consideration of the AC-2 pattern for verification of antibodies to DFS70 under routine conditions may incorrectly estimate a considerable number of not only low but also high titer anti-DSF70 positive sera. The significance of RIPA reactive antibodies, especially of low titer range, in the context of SARD and healthy individuals now has to be scrutinized in further clinical studies.

Determination of the Variance of Complex Calculated Clinical Chemistry Tests; Application in Calculated Low Density Lipoprotein and Atherogenic Index of Plasma

Determination of the Variance of Complex Calculated Clinical Chemistry Tests; Application in Calculated Low Density Lipoprotein and Atherogenic Index of Plasma

Clinical Application of Overlapping Confidence Intervals for Monitoring Changes in Serial Clinical Chemistry Test Results.

BackgroundInterpretation of changes in serial laboratory results is necessary for both clinicians and laboratories; however, setting decision limits is not easy. Although the reference change value (RCV) has been widely used for auto-verification, it has limitations in clinical settings. We introduce the concept of overlapping confidence intervals (CIs) to determine whether the changes are statistically significant in clinical chemistry laboratory test results.MethodsIn total, 1,202,096 paired results for 33 analytes routinely tested in our clinical chemistry laboratory were analyzed. The distributions of delta% absolute values and cut-off values for certain percentiles were calculated. The CIs for each analyte were set based on biological variation, and data were analyzed at various confidence levels. Additionally, we analyzed the data using RCVs and compared their clinical utility.ResultsMost analytes had low indexes of individuality with large inter-individual variability. The 97.5th percentile cut-offs for each analyte were much larger than conventional RCVs. The percentages of results exceeding RCV95% and RCV99% corresponded to those with no overlap at the 83.4% and 93.2% confidence levels, respectively.ConclusionsThe use of overlapping CIs in serial clinical chemistry test results can overcome the limitations of existing RCVs and replace them, especially for analytes with large intra-individual variation.

Evaluation of the clinical chemistry tests analytical performance by using different models and specifications

Abstract Background The importance of managing analytical quality in clinical laboratories is known. Goal-setting models are critical for analytical quality management, along with correctly implemented error models. However, the methods used to determine analytical performance and more importantly, the relevant analytical quality goals are open to discussion. Our aim was to compare the analytical performance characteristics of routine clinical chemistry tests with different goal-setting models which was proposed by various establishments. In addition, to provide a perspective to Turkish total analytical error (TAE) circular letter that compulsory to calculate from 2016. Materials and methods This study was performed by the data obtained from the internal and external quality control of clinical chemistry tests which were measured by Roche Cobas c501 biochemistry analyzer. TAE calculated with TAE% = 1.65 ×(CV%) + Bias% formula. Nordtest uncertainty model was used in the calculation of measurement uncertainty (MU). In this context, total analytical error was evaluated with biological variation (BV), RCPA, CLIA and Turkish allowable total error (ATE) goals. Measurement uncertainty was evaluated with only permissible measurement uncertainty (pU%) goal. Results In our study, RCPA goals are the most stringent, followed by the BVEuBIVAS, BVRicos, pU%, CLIA and finally the ATETurkey goals coming in last. In cumulatively, BVEuBIVAS goals were 18.3% lower than BVRicos for evaluated parameters. Conclusion The balance between applicability and analytical assurance of goals should be well ensured when determining goal-setting models. Circular letter (2016/18) creates awareness to the analytical quality management but still open to development. Biological variation dependent total allowable error model never designed to be used as benchmarks for measurement uncertainty and it is not methodologically appropriate for assessing measurement uncertainty which was estimated by the Nordtest method. Also considered that, the use of “permissible MU” is more methodologically appropriate in the evaluation of measurement uncertainty.

Effects of commonly used medicinal herbs in Jordan on serum total antioxidant status and clinical laboratory testing

The use of medicinal herbs is widespread and growing. We tested the in-vivo effects of commonly used medicinal herbs in Jordan, on normal human volunteers after oral administration of aqueous extracts for several days, to see whether the in-vitro chemical antioxidant activity of a given herb replicates in-vivo and to see whether a given medicinal herb affects the results of selected clinical chemistry tests performed on the serum. Healthy volunteers were given orally aqueous herbal extracts daily for five days. Venous blood samples were taken before and one hour after the first dose of aqueous extract and then one day after the last dose of day five. Total antioxidant status and 13 of routine clinical chemistry tests were assayed on the serum. The tested herbs caused a significant increase in serum total antioxidant status. The studied herbs can be arranged in decreasing order of their in-vivo antioxidant strength after one hour of first consumption as follows: Nigella sativum &gt; Rosmarinus officinalis &gt; Zingiber officinale &gt; Verbena triphylla &gt; Origanum syriacum &gt; Salvia triloba. The studied herbs except for Rosmarinus officinalis also caused a significant increase and/or decrease in 10 out of 13 laboratory tests performed on the serum. These results indicate that oral administration of aqueous extracts of medicinal herbs although improve the serum total antioxidant status, they could also significantly alter some laboratory results used for diagnosis or evaluation of diseases and this may negatively affect patient’s care. The present study highlights the importance of obtaining information regarding patients’ uptake of herbal products that might interfere with some laboratory testing.

The performance evaluation of unassayed biochemistry serum controls

Objective To evaluate the inter-bottle variations, stability in consumption and interchangeability of unassayed biochemistry serum controls. Methods Comparison between unassayed serum controls from a domestic Pretrol® and an international Bio-Rad manufacturer was conducted in department of laboratory, in May 2016, with Roche Cobas 8000, Roche Hitachi 7600 and Siemens 2400 modular analyzer. The inter-bottle variation was determined by monitoring the inter-batch variation of 10 bottles of control samples after eliminating the intra-batch variation from the same bottle. Stability in consumption was determined as the precision after 7 days storage under 2 ℃ to 8 ℃ or 30 days of storage under -20 ℃ since reconstitution. The interchangeability was determined as the precisionbetween the controls from different manufacturers for the same test. Results The inter-bottle imprecision of controls from domestic manufacturer for 13 biochemistry tests (CV concentration 1/CV concentration 2) were potassium (0.26%/0.42%), sodium (0.26%/0.21%), phosphorus (0.00%/0.62%), cholesterol (0.56%/0.54%), total protein (0.52%/0.33%), albumin (0.44%/2.00%), alanine aminotransferase (1.72%/0.57%), γ-glutamylaminotransferase (0.52%/0.62%), aspartate aminotransferase (3.10%/1.09%), lactate dehydrogenase (0.76%/0.91%), alkaline phosphatase (1.13%/0.97%), amylase (0.30%/0.39%) and glucose (0.00%/0.40%). The stability in consumption of the controls from the domestic manufacturer (CV concentration 1/CV concentration 2 under 2 ℃ to 8 ℃storage; CV concentration 1/CV concentration 2 under -20 ℃ storage) were potassium (1.06%/0.36%; 0.74%/0.48%), sodium (0.49%/0.59%; 0.72%/0.65%), phosphorus (0.95%/0.80%; 1.43%/0.84%), cholesterol (1.49%/1.58%; 2.17%/1.80%), total protein (0.84%/0.75%; 1.60%/1.68%), albumin (1.33%/2.28%; 1.94%/2.43%), alanine aminotransferase (1.41%/0.51%; 3.24%/1.60%) γ-glutamylaminotransferase (1.16%/1.16%; 2.85%/2.49%), aspartate aminotransferase (4.37%/2.14%; 2.99%/1.31%), lactate dehydrogenase (2.70%/2.54%; 3.84%/2.97%), alkaline phosphatase (2.63%/1.96%; 2.31%/2.10%), amylase (0.95%/2.19%; 1.58%/1.38%) and glucose (0.60%/0.48%; 1.41%/1.55%). The Inter-bottle variation and stability in consumption of biochemistry test unassayed controls from the domestic manufacturer were compatible for clinical assay according to the CV% specification from the Clinical Biochemistry Test Quality Requirement (WS/T 403-2012). The imprecision of the controls from both the domestic and international manufacturers (CVp concentration 1/CVp concentration2; CVq concentration 1/CVq concentration 2) were potassium (0.52%/0.46%; 2.39%/0.47%), sodium (0.30%/0.17%; 0.81%/0.47%), phosphorus (2.72%/1.11%; 4.57%/2.07%), cholesterol (0.29%/1.38%; 2.94%/1.81%), total protein (0.66%/2.46%; 1.85%/2.54%), alkaline phosphatase (2.67%/4.66%; 3.58%/8.55%), total bilirubin (5.71%/5.09%; 9.55%/7.41%), albumin (1.10%/2.61%; 4.79%/1.93%), alanine aminotransferase (6.42%/1.25%; 5.74%/1.63%), γ-glutamylaminotransferase (2.27%/4.35%; 4.38%/0.74%), aspartate aminotransferase (0.56%/2.84%; 0.91%/2.11%) and lactate dehydrogenase (2.36%/2.47%; 3.10%/1.52%). The interchangeability of serum controls from domestic manufacturer was better than clinical serum samples. Conclusion The unassayed serum biochemistry test controls from domestic manufacturer are suitable for the intra-laboratory quality control and showed a promising compatibility for inter-laboratory quality control usage. Key words: Quality control; Clinical chemistry tests; Diagnostic tests,routine; Clinical laboratory techniques

Effect of pH on the Quantification of Body Fluid Analytes for Clinical Diagnostic Testing

Abstract Background Body fluid samples (BFs) with low pH have demonstrated underrecovery of enzyme activity. The aims of this study were (1) measure the frequency of abnormal pH in BFs received for clinical chemistry testing, (2) calculate recovery of analytes in BFs undergoing pH titration, and (3) investigate the mechanism of pH interference. Methods Residual BFs submitted for physician-ordered testing to the Central Clinical Laboratory (Mayo Clinic) were utilized for this study. BFs were centrifuged 10 minutes (3,200 rpm) prior to pH measurement (pH meter, Accumet X15; Fisher Scientific) and analysis. A Roche Cobas c501 (Roche Diagnostics) analyzer was used to measure amylase, lactate dehydrogenase (LDH), blood urea nitrogen (BUN), creatinine, glucose, albumin, total protein, bilirubin (all Roche Diagnostics reagents), and lipase (Sekisui Diagnostics). pH was measured in 122 BFs received between 10/23/2018 and 10/26/2018 within 24 hours of receipt. pH titration was performed using pooled BFs of similar source/type. Each pool was titrated over a range of pH (≤2 to ≥10) in 1-unit increments by addition of a fixed volume of acid (6M HCL) or base (6M NaOH). Analytes were measured before and after acid/base addition. Average percent recovery was calculated (measured/expected × 100%) from n = 3 to 9 pH measurements. A low pH BF pool was spiked (&lt;5% by volume) with a high-concentration BF to investigate mechanism of enzyme underrecovery. Additionally, low pH BF pool was neutralized by addition of base and % recovery calculated. For all titration/spiking experiments, a control sample having the same volume of diluent (7% bovine serum albumin or saline) was used to account for the effects of dilution. Results BFs received (n = 122) had mean (SD) pH = 8.0 (0.6) with 6.6% (n = 8) having pH &lt;7.0 and 2.5% (n = 3) having pH &lt;6.0. All recovery (%) and pH data are expressed as mean (range) values. Amylase recovery (initial pH = 8.4-8.9) was 1.3 (0.9-2.2)% at pH = 1.6 (1.0-2.2) (n = 6), 55.6 (37.4-67.0)% at pH = 4.4 (3.5-5.4) (n = 6), 81.4 (74.0-85.2)% at pH = 6.2 (6.1-6.5) (n = 3), 90.1 (84.4-95.4)% at pH = 7.5 (7.3-7.7) (n = 3), 98.8 (96.2-101.7)% at pH = 10.0 (9.8-10.2) (n = 3), and 14.5 (1.4-38.9)% at pH = 11.9 (11.5-12.1) (n = 3). LDH recovery (initial pH = 8.2-8.5) was 1.4 (0.1-3.7)% at pH = 1.7 (1.0-2.4) (n = 6), 18.3 (0.5-39.7)% at pH = 4.5 (3.5-5.4) (n = 6), 63.6 (54.9-68.4)% at pH = 6.2 (6.1-6.5) (n = 3), 85.9 (80.2-90.7)% at pH = 7.2 (6.8-7.4) (n = 3), 46.1 (36.4-61.0)% at pH = 10.0 (9.8-10.2) (n = 3), and 9.8 (0.0-28.9)% at pH = 11.3 (10.4-12.1) (n = 3). Lipase recovery (initial pH = 8.2-8.9) was 10.4 (&lt;1-18)% at pH = 1.8 (1.0-2.4) (n = 6), 73.9 (62.6-85.5)% at pH = 4.2 (3.4-5.2) (n = 3), 92.4 (90.8-93.5)% at pH = 6.2 (6.0-6.5) (n = 3), 96.3 (95.6-96.8)% at pH = 7.3 (6.8-7.7) (n = 3), and 92.9 (89.3-96.8)% at pH = 9.9 (9.8-10.1) (n = 3) and 80.9 (0.0-78.6)% at pH = 11.3 (10.4-12.1) (n = 3). Creatinine, BUN, albumin, glucose, total protein, and bilirubin recovery were 97.9 (92.2-102.9)%, 100 (96.6-103.1)%, 99.9 (97.6-102.4)%, 100.2 (97.8-103)%, 100.2 (98.7-101.9)%, and 100.1 (92.-105.9)%, respectively, between pH 1.3-11.7 (n = 9). Recovery of amylase, LDH, or lipase was &lt;1% after spiking enzymes into BF pool with pH &lt;3. pH adjustment to normal (pH = 8.6-9.0) also resulted in recovery of &lt;1%. Conclusion Enzyme activity in BFs was not affected (90%-110% recovery) when pH = 7.4-8.5 for LDH, pH = 7.3-10.2 for amylase, pH = 6.0-9.9 for lipase, and pH = 1.3-11.7 for all other analytes. An irreversible loss of enzyme activity occurs at low pH. Few clinical BFs have pH &lt;7.0, but laboratories should have awareness.