In this era of precision medicine, molecular biology is becoming increasingly significant for the diagnosis and therapeutic management of non-small cell lung cancer. The specimen as the primary element of the whole testing flow is particularly important for maintaining the accuracy of gene alteration testing. Presently, the main sample types applied in routine diagnosis are tissue and cytology biopsies. Liquid biopsies are considered as the most promising alternatives when tissue and cytology samples are not available. Each sample type possesses its own strengths and weaknesses, pertaining to the disparity of sampling, preparation and preservation procedures, the heterogeneity of inter- or intratumors, the tumor cellularity (percentage and number of tumor cells) of specimens, etc., and none of them can individually be a “one size to fit all”. Therefore, in this review, we summarized the strengths and weaknesses of different sample types that are widely used in clinical practice, offered solutions to reduce the negative impact of the samples and proposed an optimized strategy for choice of samples during the entire diagnostic course. We hope to provide valuable information to laboratories for choosing optimal clinical specimens to achieve comprehensive functional genomic landscapes and formulate individually tailored treatment plans for NSCLC patients that are in advanced stages.

Publicly Available May 5, 2017

The impact of pneumatic tube system on routine laboratory parameters: a systematic review and meta-analysis

Georgia V. Kapoula, Panagiota I. Kontou, Pantelis G. Bagos

Page range: 1834-1844

More Download PDF

Abstract

Background: Pneumatic tube system (PTS) is a widely used method of transporting blood samples in hospitals. The aim of this study was to evaluate the effects of the PTS transport in certain routine laboratory parameters as it has been implicated with hemolysis. Methods: A systematic review and a meta-analysis were conducted. PubMed and Scopus databases were searched (up until November 2016) to identify prospective studies evaluating the impact of PTS transport in hematological, biochemical and coagulation measurements. The random-effects model was used in the meta-analysis utilizing the mean difference (MD). Heterogeneity was quantitatively assessed using the Cohran’s Q and the I 2 index. Subgroup analysis, meta-regression analysis, sensitivity analysis, cumulative meta-analysis and assessment of publication bias were performed for all outcomes. Results: From a total of 282 studies identified by the searching procedure, 24 were finally included in the meta-analysis. The meta-analysis yielded statistically significant results for potassium (K) [MD=0.04 mmol/L; 95% confidence interval (CI)=0.015–0.065; p=0.002], lactate dehydrogenase (LDH) (MD=10.343 U/L; 95% CI=6.132–14.554; p<10 −4 ) and aspartate aminotransferase (AST) (MD=1.023 IU/L; 95% CI=0.344–1.702; p=0.003). Subgroup analysis and random-effects meta-regression analysis according to the speed and distance of the samples traveled via the PTS revealed that there is relation between the rate and the distance of PTS with the measurements of K, LDH, white blood cells and red blood cells. Conclusions: This meta-analysis suggests that PTS may be associated with alterations in K, LDH and AST measurements. Although these findings may not have any significant clinical effect on laboratory results, it is wise that each hospital validates their PTS.

Opinion Paper

Publicly Available October 14, 2017

How to reduce scientific irreproducibility: the 5-year reflection

Clare Fiala, Eleftherios P. Diamandis

Page range: 1845-1848

More Download PDF

Abstract

We discuss in depth six causes of scientific irreproducibility and their ramifications for the clinical sciences: fraud, unfounded papers published by prominent authorities, bias, technical deficiencies, fragmented science and problems with big data. Some proposed methods to combat this problem are briefly described, including an effort to replicate results from some high impact papers and a proposal that authors include detailed preclinical data in papers with supposedly high translational value. We here advocate for a 5-year reflection on papers with seemingly high clinical/translational potential, published alongside the original paper where authors reflect on the quality, reproducibility and impact of their findings. These reflections can be used as a benchmark for credibility, and begin a virtuous cycle of improving the quality of published findings in the literature.

EFLM Paper

Publicly Available October 14, 2017

Strategies to define performance specifications in laboratory medicine: 3 years on from the Milan Strategic Conference

Mauro Panteghini, Ferruccio Ceriotti, Graham Jones, Wytze Oosterhuis, Mario Plebani, Sverre Sandberg, on behalf of the Task Force on Performance Specifications in Laboratory Medicine of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Page range: 1849-1856

More Download PDF

Abstract

Measurements in clinical laboratories produce results needed in the diagnosis and monitoring of patients. These results are always characterized by some uncertainty. What quality is needed and what measurement errors can be tolerated without jeopardizing patient safety should therefore be defined and specified for each analyte having clinical use. When these specifications are defined, the total examination process will be “fit for purpose” and the laboratory professionals should then set up rules to control the measuring systems to ensure they perform within specifications. The laboratory community has used different models to set performance specifications (PS). Recently, it was felt that there was a need to revisit different models and, at the same time, to emphasize the presuppositions for using the different models. Therefore, in 2014 the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) organized a Strategic Conference in Milan. It was felt that there was a need for more detailed discussions on, for instance, PS for EQAS, which measurands should use which models to set PS and how to set PS for the extra-analytical phases. There was also a need to critically evaluate the quality of data on biological variation studies and further discussing the use of the total error (TE) concept. Consequently, EFLM established five Task Finish Groups (TFGs) to address each of these topics. The TFGs are finishing their activity on 2017 and the content of this paper includes deliverables from these groups.

General Clinical Chemistry and Laboratory Medicine

May 5, 2017

Intensive educational efforts combined with external quality assessment improve the preanalytical phase in general practitioner offices and nursing homes

Una Ørvim Sølvik, Wenche Iren Bjelkarøy, Kari van den Berg, Anne Lise Saga, Helle Borgstrøm Hager, Sverre Sandberg

Page range: 1857-1864

Abstract

Background: Errors in the preanalytical phase in clinical laboratories affect patient safety. The aim of this study was to evaluate the effect of intensive educational efforts together with external quality assessment (EQA) of the preanalytical phase from 2013 to 2015 to improve patient identification in primary health care in Norway. In addition, routines for venous and capillary blood sampling were investigated. Methods: A preanalytical EQA was circulated in 2013 by the Norwegian Quality Improvement of Laboratory Examinations (Noklus) to general practitioner offices and nursing homes (n=2000) to obtain information about important issues to focus on before launching an intensive educational program with courses, posters and visits in 2013–2015. Preanalytical EQA surveys were further circulated in 2014 and 2015. Results: The response rate varied between 42% and 55%. The percentages of participants asking for the patients’ name and the Norwegian identification number increased from about 8% in 2013 to about 35% in 2015. The increase was similar for those participating in only one EQA survey and for those who participated in EQA surveys both in 2013 and 2015. Guidelines for venous and capillary blood sampling were not always followed. Conclusions: Educational efforts more than the preanalytical EQA influenced the actions and resulted in an increase in the percentages of participants that followed the guidelines for patient identification. Some aspects of blood sampling routines need improvement.

April 27, 2017

Separate patient serum sodium medians from males and females provide independent information on analytical bias

Steen Ingemann Hansen, Per Hyltoft Petersen, Flemming Lund, Callum G. Fraser, György Sölétormos

Page range: 1865-1872

Abstract

Background: During monitoring of monthly medians of results from patients undertaken to assess analytical stability in routine laboratory performance, the medians for serum sodium for male and female patients were found to be significantly related. Methods: Daily, weekly and monthly patient medians of serum sodium for both male and female patients were calculated from results obtained on samples from the population >18 years on three analysers in the hospital laboratory. The half-range of medians was applied as an estimate of the maximum bias. Further, the ratios between the two medians were calculated. Results: The medians of both genders demonstrated dispersions over time, but they were closely connected in like patterns, which were confirmed by the half-range of the ratios of medians for males and females that varied from 0.36% for daily, 0.14% for weekly and 0.036% for monthly ratios over all instruments. Conclusions: The tight relationship between the gender medians for serum sodium is only possible when raw laboratory data are used for calculation. The two patient medians can be used to confirm both and are useful as independent estimates of analytical bias during constant calibration periods. In contrast to the gender combined median, the estimate of analytical bias can be confirmed further by calculation of the ratios of medians for males and females.

April 17, 2017

Are admission procalcitonin levels universal mortality predictors across different medical emergency patient populations? Results from the multi-national, prospective, observational TRIAGE study

Ramon Sager, Yannick Wirz, Devendra Amin, Adina Amin, Pierre Hausfater, Andreas Huber, Sebastian Haubitz, Alexander Kutz, Beat Mueller, Philipp Schuetz

Page range: 1873-1880

Abstract

Background: Procalcitonin (PCT), an inflammatory blood biomarker, is well studied in infectious diseases. Its prognostic value in unselected emergency department (ED) patients remains yet undefined. Herein, we investigated association of admission PCT levels and mortality in a large, international-multicenter ED patient cohort. Methods: We prospectively enrolled 6970 unselected, consecutive, adult, medical patients seeking ED care in three tertiary-care hospitals in Switzerland, France and the USA. We used multivariable logistic regression models to examine association of admission PCT levels (as a continuous predictor and across cut-offs) and 30-day mortality. We also investigated subgroup effects by main diagnosis, comorbidities and clinical features at presentation. Results: During the 30-day follow-up, 328 (4.7%) participants died. Mortality increased stepwise within higher PCT cut-offs (0.05, 0.1, 0.25, 0.5 ng/mL) from 1%, 3%, 7%, 13% to 15%, respectively. This association was also confirmed in a fully-adjusted model including age, gender, main symptom, main diagnosis and vital parameters on admission. Receiver operating characteristic (ROC) curve analysis showed that PCT differentiated well between survivors and non-survivors in the overall cohort (area under ROC curve [AUC] 0.75) with best results for patient with metabolic (AUC: 0.85) and cardiovascular disease (AUC: 0.82). Addition of PCT also improved the prognostic accuracy of the quick sequential organ failure assessment (qSOFA) score from an AUC of from 0.61 to 0.76 (p<0.001). Results were similar for other secondary endpoints including intensive care unit (ICU) admission and hospital readmission. Conclusions: In this large and heterogenous medical ED patient cohort, admission PCT was a strong and independent outcome predictor for 30-day mortality across different medical diagnoses independent of underlying infection. PCT may help to improve risk stratification in unselected medical ED patients.

March 15, 2017

Biochemical testing in a laboratory tent and semi-intensive care of Ebola patients on-site in a remote part of Guinea: a paradigm shift based on a bleach-sensitive point-of-care device

Leonid M. Irenge, Jean-Michel Dindart, Jean-Luc Gala

Page range: 1881-1890

Abstract

Abstract: Background: During the West Africa Ebola virus disease (EVD) outbreak, a Belgian laboratory was deployed for supporting the Ebola treatment unit (ETU) of N’Zerekore, Guinea. Besides diagnosis of EVD and malaria, biochemical parameters were tested and used to guide supportive treatment of EVD. Methods: To preserve analytes stability, lithium-heparin blood samples were analyzed using the i-STAT ® point-of-care testing (POCT) handheld device without the viral inactivation step. To mitigate the risk of Ebola virus transmission, assays were performed inside a portable glovebox with strict biosafety procedures. Results: Providing the medical staff with real-time biochemical data modified their therapeutic attitude, shifting from empiric to a semi-intensive laboratory-guided treatment of hydro-electrolytic disturbances, metabolic acidosis and/or impaired kidney function. As illustrated with representative EVD cases (n=8), optimized supportive treatment with intravenous fluid therapy and electrolyte replacement often helped correct these abnormalities. However, the harsh operating conditions, especially the use of bleach decontamination inside the glovebox, caused several technical failures and the final breakdown of the POCT device. Conclusions: POCT availability resulted in a paradigm shift in laboratory practice and care delivery at the N’Zerekore ETU. We conclude that there is urgent need for novel well-designed and validated POCT devices usable by non-expert operators in high ambient temperature and limited space. These devices should withstand regular and thorough decontamination by the personnel working on-site with life-threatening pathogens and be compatible with high biosafety level procedures. Such specific users’ requirements need a European validation and standardization process of proposed solutions led by the EU Standardization Committee (CEN).

March 15, 2017

Efficient reporting of the estimated glomerular filtration rate without height in pediatric patients with cancer

Tae-Dong Jeong, Eun-Jung Cho, Woochang Lee, Sail Chun, Ki-Sook Hong, Won-Ki Min

Page range: 1891-1897

Abstract

Abstract: Background: The updated bedside Schwartz equation requires constant, serum creatinine concentration and height measurements to calculate the estimated glomerular filtration rate (eGFR) in pediatric patients. Unlike the serum creatinine levels, obtaining height information from the laboratory information system (LIS) is not always possible in a clinical laboratory. Recently, the height-independent eGFR equation, the full age spectrum (FAS) equation, has been introduced. We evaluated the performance of height-independent eGFR equation in Korean children with cancer. Methods: A total of 250 children who underwent chromium-51-ethylenediamine tetra acetic-acid ( 51 Cr-EDTA)-based glomerular filtration rate (GFR) measurements were enrolled. The 51 Cr-EDTA GFR was used as the reference GFR. The bias (eGFR – measured GFR), precision (root mean square error [RMSE]) and accuracy (P30) of the FAS equations were compared to those of the updated Schwartz equation. P30 was defined as the percentage of patients whose eGFR was within ±30% of the measured GFR. Results: The FAS equation showed significantly lower bias (mL/min/1.73 m 2 ) than the updated Schwartz equation (4.2 vs. 8.7, p<0.001). The RMSE and P30 were: updated Schwartz of 43.8 and 64.4%, respectively, and FAS of 42.7 and 66.8%, respectively. Conclusions: The height-independent eGFR-FAS equation was less biased and as accurate as the updated Schwartz equation in Korean children. The use of the height-independent eGFR equation will allow for efficient reporting of eGFR through the LIS in clinical laboratories.

March 15, 2017

Evaluation of thyroid test utilization through analysis of population-level data

Jasmine Gill, Vilte E. Barakauskas, Dylan Thomas, Karina Rodriguez-Capote, Trefor Higgins, Don Zhang, Amanda VanSpronsen, Oksana Babenko, Roberta Martindale, Mathew P. Estey

Page range: 1898-1906

Abstract

Abstract: Background: Inappropriate laboratory test utilization can result in unnecessary patient testing and increased healthcare costs. While several thyroid function tests are available, thyroid-stimulating hormone (TSH) is recommended as the first-line test for investigating and monitoring thyroid dysfunction. We evaluate thyroid test utilization in Northern Alberta in terms of testing patterns, frequencies, and reflex cutpoints. Methods: This retrospective study analyzed thyroid test requests from January to December 2014. Each request was designated as appropriate or potentially inappropriate as per clinical practice guidelines and Choosing Wisely recommendations, and the frequencies of each testing pattern were calculated. Sub-analysis was performed to categorize testing patterns based on physician specialty. The number of test requests per patient was determined to assess the appropriateness of testing frequency. Receiver operating characteristic (ROC) curves were generated to define optimal TSH cutpoints for automatic reflex to FT4 testing. Results: Of 752,217 test requests, approximately 10% were potentially inappropriate in terms of testing patterns. Free thyroxine (FT4) and free triiodothyronine (FT3) requested with TSH accounted for 59% of all potentially inappropriate test requests, and 49% of requests from endocrinologists (ENDO) were potentially inappropriate, occurring most frequently among those with less experience. Excessive testing frequencies were observed in 869 patients, accounting for 9382 test requests. Adjustment of our TSH reflex cutpoint would significantly increase specificity for identifying a low FT4 without compromising sensitivity. Conclusions: This study suggests that questionable testing patterns, excessive testing frequencies, and suboptimal reflexive testing cutpoints contribute to inappropriate thyroid test utilization.

March 7, 2017

Relation of serum γ-glutamyl transferase activity with copper in an adult population

You-Fan Peng, Chun-Fang Wang, Guo-Gang Pan

Page range: 1907-1911

Abstract

Background: The aim of this study was to evaluate the relationship between serum γ-glutamyl transferase (γ-GGT) activity and serum copper in an adult population. Methods: We analyzed 281 adult subjects who regularly attended the physical examination center at the Affiliated Hospital of Youjiang Medical University for Nationalities. Results: The demographic and laboratory data of the participants were divided into two groups according to the median of serum γ-GGT activity. Serum copper concentrations in individuals with higher γ-GGT levels were significantly increased compared with those with lower γ-GGT concentrations (9.9±2.41 vs. 11.2±3.36 μmol/L, p<0.001). There was a positive correlation between serum γ-GGT activity and copper in all eligible subjects (r=0.198, p=0.001). Further, serum γ-GGT maintained a positive correlation with serum copper in both males and females (r=0.322, p<0.001; r=0.230, p=0.010). The results of multiple linear regression analysis showed that serum γ-GGT maintained a significantly positive correlation with copper after adjusting for multiple potential confounders (b=0.464, p=0.001). Conclusions: This study suggests that serum γ-GGT activity is correlated with copper in the study population, indicating that serum γ-GGT may be a biomarker to evaluate serum copper levels in an adult population.

Publicly Available March 22, 2017

Impact of a single oral dose of 100,000 IU vitamin D3 on profiles of serum 25(OH)D3 and its metabolites 24,25(OH)₂D3, 3-epi-25(OH)D3, and 1,25(OH)₂D3 in adults with vitamin D insufficiency

Lanja Saleh, Jonathan Tang, Joanna Gawinecka, Lukas Boesch, William D. Fraser, Arnold von Eckardstein, Albina Nowak

Page range: 1912-1921

More Download PDF

Abstract

Background: We investigate the effect of a high dose of vitamin D3 on circulating concentrations of 25(OH)D3 and its metabolites 24,25(OH) 2 D3, 3-epi-25(OH)D3, and 1,25(OH) 2 D3 in healthy individuals with self-perceived fatigue and vitamin D insufficiency [25(OH)D3<50 nmol/L]. Methods: One hundred and seven study participants (age 20–50 years) were randomized to receive a single 100,000 IU dose of vitamin D3 (n=52) or placebo (n=55). Vitamin D metabolite concentrations in serum were measured before, and 4 weeks after, supplementation. Results: Overall, 52% of participants receiving vitamin D3 attained a serum 25(OH)D3 level >75 nmol/L. Among individuals who received vitamin D3, there were significant increases in serum concentrations of 25(OH)D3 and its metabolites 24,25(OH) 2 D3, 3-epi-25(OH)D3, and 1,25(OH) 2 D3 at 4 weeks; however, inter-individual variability in these changes was substantial. Positive correlations between serum 25(OH)D3 and 24,25(OH) 2 D3 and 3-epi-25(OH)D3, and a significant negative correlation between serum 1,25(OH) 2 D3 and 3-epi-25(OH)D3, were found 4 weeks after supplementation. The 24,25(OH) 2 D3/25(OH)D3 and 24,25(OH) 2 D3/1,25(OH) 2 D3 ratios were significantly increased, compared with baseline, in participants receiving vitamin D3. Baseline 25(OH)D3 concentration was the only factor predictive of the change in 25(OH)D3 after supplementation. Conclusions: Administration of a single high dose of vitamin D3 leads to a significant increase in concentrations of 25(OH)D3, 24,25(OH) 2 D3, 3-epi-25(OH)D3 and 1,25(OH) 2 D3; induction of the catabolic pathway predominates over the production of 1,25(OH) 2 D3. Due to the high inter-individual variation in the 25(OH)D3 response to supplementation, any given dose of vitamin D is unlikely to achieve optimal vitamin D status in all treated individuals

Publicly Available May 3, 2017

Automated antinuclear immunofluorescence antibody analysis is a reliable approach in routine clinical laboratories

Bing Zheng, Enling Li, Haoming Zhu, Jingbo Lu, Xinming Shi, Jie Zhang, Min Li

Page range: 1922-1930

More Download PDF

Abstract

Background: Indirect immunofluorescence (IIF) assays are recommended as the gold standard method for the detection of antinuclear antibodies (ANAs). This study aimed to investigate the reliability of an automated system. Methods: We compared 3745 serum samples using NOVA View archived images with manual analysis via microscopy. A custom cutoff value was established to distinguish ANA titers and was validated in two clinical laboratories. The automatic ANA pattern recognition system was evaluated, and all ANA-positive sera were subjected to two commercial ANA IIF kits to compare the consistency of the pattern interpretation results. For inconsistent patterns, a third ANA IIF testing kit was utilized. Results: Agreement of the interpretation of the ANA IIF test using the platform of NOVA View and manual microscopy was 96.9%. The local cutoff value to discriminate ANA titers in four main ANA patterns was calculated based on 1390 serum samples. In our laboratory, the titer prediction accuracy was superior to the preset cutoff in NOVA View (p<0.01); the performance was similar in another laboratory (p=0.11). The automatic pattern recognition accuracies of speckled, homogeneous, centromere, nucleolar and nuclear dot patterns were 62.7%, 57.4%, 92.6%, 30.5% and 27.3%, respectively. The consistency of the pattern interpretation results between INOVA and MBL kits was 95.3%. Conclusions: It is necessary to establish a custom value-added ANA report. However, confirmation of the digital immunofluorescence images by expert technicians was essential, and suspect results of an ANA pattern should be reconfirmed by another commercial ANA IIF kit to achieve more reliable results.

March 15, 2017

Infrared analyzers for breast milk analysis: fat levels can influence the accuracy of protein measurements

Celia Kwan, Gerhard Fusch, Aldin Bahonjic, Niels Rochow, Christoph Fusch

Page range: 1931-1935

Abstract

Abstract: Background: Currently, there is a growing interest in lacto-engineering in the neonatal intensive care unit, using infrared milk analyzers to rapidly measure the macronutrient content in breast milk before processing and feeding it to preterm infants. However, there is an overlap in the spectral information of different macronutrients, so they can potentially impact the robustness of the measurement. In this study, we investigate whether the measurement of protein is dependent on the levels of fat present while using an infrared milk analyzer. Methods: Breast milk samples (n=25) were measured for fat and protein content before and after being completely defatted by centrifugation, using chemical reference methods and near-infrared milk analyzer (Unity SpectraStar) with two different calibration algorithms provided by the manufacturer (released 2009 and 2015). Results: While the protein content remained unchanged, as measured by elemental analysis, measurements by infrared milk analyzer show a difference in protein measurements dependent on fat content; high fat content can lead to falsely high protein content. This difference is less pronounced when measured using the more recent calibration algorithm. Conclusions: Milk analyzer users must be cautious of their devices’ measurements, especially if they are changing the matrix of breast milk using more advanced lacto-engineering.

Hematology and Coagulation

March 16, 2017

A new approach to define acceptance limits for hematology in external quality assessment schemes

Mohamed Rida Soumali, Marjan Van Blerk, Abdelhadi Akharif, Stéphanie Albarède, Dagmar Kesseler, Gabriela Gutierrez, Barbara de la Salle, Inger Plum, Anne Guyard, Ana Paula Favia, Wim Coucke

Page range: 1936-1942

Abstract

Abstract: Background: A study performed in 2007 comparing the evaluation procedures used in European external quality assessment schemes (EQAS) for hemoglobin and leukocyte concentrations showed that acceptance criteria vary widely. For this reason, the Hematology working group from the European Organisation for External Quality Assurance Providers in Laboratory Medicine (EQALM) decided to perform a statistical study with the aim of establishing appropriate acceptance limits (AL) allowing harmonization between the evaluation procedures of European EQAS organizers. Methods: Eight EQAS organizers from seven European countries provided their hematology survey results from 2010 to 2012 for red blood cells (RBC), hemoglobin, hematocrit, mean corpuscular volume (MCV), white blood cells (WBC), platelets and reticulocytes. More than 440,000 data were collected. The relation between the absolute value of the relative differences between reported EQA results and their corresponding assigned value (U-scores) was modeled by means of an adaptation of Thompson’s “characteristic function”. Quantile regression was used to investigate the percentiles of the U-scores for each target concentration range. For deriving AL, focus was mainly on the upper percentiles (90th, 95th and 99th). Results: For RBC, hemoglobin, hematocrit and MCV, no relation was found between the U-scores and the target concentrations for any of the percentiles. For WBC, platelets and reticulocytes, a relation with the target concentrations was found and concentration-dependent ALs were determined. Conclusions: The approach enabled to determine state of the art-based ALs, that were concentration-dependent when necessary and usable by various EQA providers. It could also easily be applied to other domains.

May 5, 2017

The effects of transport by car on coagulation tests

Merve Ergin, Serpil Erdogan, Onur Akturk, Ozcan Erel

Page range: 1943-1947

Abstract

Background: This research investigated the effects of the transport of blood samples between centers/laboratories by car on coagulation tests. Methods: Five tubes of blood samples were taken from 20 healthy volunteers. The samples consisted of a baseline (control) group, centrifuged and noncentrifuged transported samples; centrifuged and noncentrifuged untransported samples. The groups of centrifuged and noncentrifuged samples were transported by car for 2 h. The centrifuged and noncentrifuged untransported samples were incubated in the laboratory until the transported samples arrived. Prothrombin time (PT) and activated partial thromboplastin time (APTT) tests were conducted for all samples. Results: Significant differences between the baseline group and the centrifuged and noncentrifuged transported samples and the noncentrifuged untransported samples were found for APTT levels (p<0.05, for all). In addition, significant mean percentage differences in PT values were found between the baseline group and the noncentrifuged transported samples (p<0.001) and the noncentrifuged untransported samples (p=0.005). The mean level of PT in the noncentrifuged transported samples was outside the upper limit of the clinical decision level. Conclusions: Noncentrifuged transported samples showed clinically significant differences in PT test results that may have stemmed from mechanical agitation during transportation. Therefore, we recommend not transporting noncentrifuged specimens for PT testing by car.

April 17, 2017

Combined measurement of factor XIII and D-dimer is helpful for differential diagnosis in patients with suspected pulmonary embolism

Ning Tang, Ziyong Sun, Dengju Li, Jun Yang, Shiyu Yin, Qing Guan

Page range: 1948-1953

Abstract

Background: D-dimer has been used to rule out pulmonary embolism (PE). Based on previous reports of decreased concentrations of coagulation factor XIII (FXIII) in venous thromboembolism, and no change in FXIII concentration in patients with acute cardiovascular disease, we evaluated the benefit of simultaneously measuring D-dimer and FXIII concentrations for diagnosing PE. Methods: In this prospective single-center study, we enrolled 209 patients initially suspected of having PE, and measured their D-dimer and FXIII concentrations. Forty-one patients were diagnosed with PE and 168 with other final diagnoses, including acute coronary syndrome (ACS); aortic dissection (AD); spontaneous pneumothorax (SP); other respiratory, heart, digestive and nervous diseases; and uncertain diagnoses. Results: Patients with PE had significantly higher D-dimer and lower FXIII concentrations than did patients without PE. Combined D-dimer and FXIII measurements provided a higher positive predictive value (76.6%) for PE than single tests, especially in patients with Wells score >4.0 (89.3%). Specifically, patients with AD or ACS showed higher FXIII concentrations and mean platelet volumes than did patients with PE or SP, and patients with PE and AD had higher D-dimer concentrations than did other patients. At the thresholds of 69.0% for FXIII and 1.10 μg/mL for D-dimer, 123/151 patients (81.5%) with serious diseases (PE, AD, ACS and SP) were correctly distinguished. Conclusions: Combined measurement of D-dimer and FXIII helps distinguish PE from serious diseases with similar symptoms and appears to relate to increased FXIII release from active platelets in cardiovascular disease.

Reference Values and Biological Variations

May 5, 2017

Influence of age, gender and body mass index on late-night salivary cortisol in healthy adults

Sabrina Coelli, Camila Bergonsi Farias, Ariana Aguiar Soares, Gabriele Martins Crescente, Vânia Naomi Hirakata, Luiza Barboza Souza, Mauro Antônio Czepielewski, Joíza Lins Camargo, Sandra Pinho Silveiro

Page range: 1954-1961

Abstract

Background: Late-night salivary cortisol (LNSC) is one of the most reliable tests to screen for endogenous Cushing syndrome. This test is simple, inexpensive and noninvasive and has high sensitivity and specificity. The aim of our study was to analyze the putative influence of age, gender and body mass index (BMI) on LNSC levels in a healthy population. Methods: Cross-sectional study conducted in healthy adults. Midnight saliva samples were collected at home. Participants refrained from teeth brushing, eating or drinking for 2 h prior to collection. Salivary cortisol measured by electrochemiluminescence immunoassay (ECLIA). The study was approved by the Ethics Committee of the hospital (number 140073). Results: We evaluated 122 nonsmoking healthy volunteers. Mean age was 35±14 years (range, 18–74 years); 63% were women. Mean BMI was 24±3 kg/m 2 , blood pressure 115/74 mmHg and fasting plasma glucose 4.8±0.5 mmol/L. LNSC presented a non-Gaussian distribution; the median was 3.58 (range, 0.55–8.55) nmol/L (0.13 [range, 0.02–0.31] μg/dL), and the 97.5th percentile (P97.5) was 8.3 nmol/L (0.3 μg/dL). Multiple linear regression disclosed a significant positive association between salivary cortisol levels and age (r 2 =0.21, p<0.001), but no association with gender (p=0.105) or BMI (p=0.119). Accordingly, participants aged >50 years had significantly higher salivary cortisol as compared to those aged <50 years (5.24 nmol/L [0.19 μg/dL] vs. 3.31 nmol/L [0.12 μg/dL], respectively, p<0.001). Conclusions: The maximum reference value (P97.5) of LNSC was set at 8.3 nmol/L (0.3 μg/dL) using ECLIA. Advanced age was associated with higher LNSC levels, with no evident influence of gender or BMI.

Cancer Diagnostics

March 17, 2017

Assessment of real-time PCR method for detection of EGFR mutation using both supernatant and cell pellet of malignant pleural effusion samples from non-small-cell lung cancer patients

Saeam Shin, Juwon Kim, Yoonjung Kim, Sun-Mi Cho, Kyung-A Lee

Page range: 1962-1969

Abstract

Background: EGFR mutation is an emerging biomarker for treatment selection in non-small-cell lung cancer (NSCLC) patients. However, optimal mutation detection is hindered by complications associated with the biopsy procedure, tumor heterogeneity and limited sensitivity of test methodology. In this study, we evaluated the diagnostic utility of real-time PCR using malignant pleural effusion samples. Methods: A total of 77 pleural fluid samples from 77 NSCLC patients were tested using the cobas EGFR mutation test (Roche Molecular Systems). Pleural fluid was centrifuged, and separated cell pellets and supernatants were tested in parallel. Results were compared with Sanger sequencing and/or peptide nucleic acid (PNA)-mediated PCR clamping of matched tumor tissue or pleural fluid samples. Results: All samples showed valid real-time PCR results in one or more DNA samples extracted from cell pellets and supernatants. Compared with other molecular methods, the sensitivity of real-time PCR method was 100%. Concordance rate of real-time PCR and Sanger sequencing plus PNA-mediated PCR clamping was 98.7%. Conclusions: We have confirmed that real-time PCR using pleural fluid had a high concordance rate compared to conventional methods, with no failed samples. Our data demonstrated that the parallel real-time PCR testing using supernatant and cell pellet could offer reliable and robust surrogate strategy when tissue is not available.

April 22, 2017

Detection of EGFR mutations in patients with non-small cell lung cancer by high resolution melting. Comparison with other methods

Carlos Martínez-Carretero, Fernando Iguaz Pascual, Antonio Rus, Ivan Bernardo

Page range: 1970-1978

Abstract

Background: The discovery of mutations in the epidermal growth factor receptor gene ( EGFR ) related to the clinical response to tyrosine kinase inhibitors, has transformed the management of non-small cell lung cancer (NSCLC). Several methods have been developed for determination of mutations in EGFR , with different sensitivity and potential ability to detect a different number of mutations. Methods: We developed a screening method by high resolution melting (HRM) to detect EGFR mutations, and compared the results of 123 fixed in formalin and paraffin embedded (FFPE) tumor tissue samples with the detection of mutations by allele-specific PCR. In samples with discordant results, Sanger and massive parallel sequencing (MPS) were additionally performed. Results: Eight samples showed discordant results between both methods. Three samples with negative results by allele specific PCR and positive by HRM were confirmed by Sanger sequencing (p.S768I+p.V769L, T751_I759del and p.E709K+p.G719A; patients 1, 3 and 4, respectively). One sample with a negative result by HRM, and positive by allele specific PCR (p.T790M; patient 2), was confirmed by Sanger sequencing. Additionally, two positive samples for a deletion in exon 19 by allele-specific PCR, were negative by Sanger sequencing and HRM (patients 2 and 5) and finally, two samples were negative by allele-specific PCR and positive by HRM and Sanger sequencing due to synonymous variants in exon 21. Conclusions: HRM is a good method for mutational screening in EGFR . It is able to detect any change in the sequence of exons 18–21, providing high cost/effectiveness, but samples with low tumor burden may produce false negatives results.

August 8, 2017

Predicting outcomes of EGFR-targeted therapy in non-small cell lung cancer patients using pleural effusions samples and peptide nucleic acid probe assay

Mei-Chia Wang, Chih-Liang Wang, Tai-Long Chen, John Wen-Cheng Chang, Jang-Jih Lu, Pi-Yueh Chang, Chiuan-Chian Chiou

Page range: 1979-1986

Abstract

Background: Mutation of epidermal growth factor receptor ( EGFR ) is a prediction marker of the response to tyrosine kinase inhibitor (TKI) drugs in non-small cell lung cancer (NSCLC) patients. As late stage lung cancer patients rarely undergo surgery, samples for EGFR mutation identification usually come from computed tomography (CT)-guided or endoscopic biopsies, which is invasive and costly. Pleural effusion may serve as a less invasive sample for EGFR mutation detection. Methods: We designed a fluorophore-labeled peptide nucleic acid (PNA) probe assay for three types of EGFR mutations, including exon 19 deletions, L858R point mutations and T790M point mutations. The assay was applied in 39 pleural effusion samples from NSCLC patients. The correlation between detected EGFR status and clinical outcome were analyzed. Results: In 15 paired samples, PNA probe assay in pleural effusion samples could detect all the mutations that were identified by conventional PCR plus Sanger sequencing in tissue biopsies. In addition, PNA probe assay detected three more T790M mutations. In all 39 pleural effusions, the PNA probe assay detected 27 having at least one of the three EGFR mutations. Among the patients before TKI treatment, those with a sensitizing mutation (either exon 19 deletion or L858R) but without T790M, had 94.1% response rate and longer progression-free survival (mean 10.8 months) than patients without detected mutation (mean 4.2 months) and patients with T790M (mean 1.7 months). Conclusions: Mutations detected in pleural effusions using PNA probe assay are highly associated with clinical outcome. This method appears to be a reliable way for the prediction of the efficacy of EGFR -targeted therapy.

June 23, 2017

Analytical and clinical performance of thyroglobulin autoantibody assays in thyroid cancer follow-up

Waddah Katrangi, Stephan K.G. Grebe, Alicia Algeciras-Schimnich

Page range: 1987-1994

Abstract

Background: While thyroglobulin autoantibodies (TgAb) can result in false low serum thyroglobulin (Tg) immunoassay (IA) measurements, they might also be indicators of disease persistence/recurrence. Hence, accurate TgAb measurement, in addition to Tg quantification, is crucial for thyroid cancer monitoring. We compared the analytical and clinical performance of four commonly used TgAb IAs. Methods: We measured Tg by mass spectrometry (Tg-MS) and by four pairs of Tg and TgAb IAs (Beckman, Roche, Siemens, Thermo) in 576 samples. Limit of quantitation (LOQ) and manufacturers’ upper reference interval cut-off (URI) were used for comparisons. Clinical performance was assessed by receiving operator characteristics (ROC) curve analysis. Results: Quantitative and qualitative agreement between TgAb-IAs was moderate with R 2 of 0.20–0.70 and κ from 0.41–0.66 using LOQ and 0.47–0.71 using URI. In samples with TgAb interference, detection rates of TgAb were similar using LOQ and URI for Beckman, Siemens, and Thermo, but much lower for the Roche TgAb-IA when the URI was used. In TgAb positive cases, the ROC areas under the curve (AUC) for the TgAb-IAs were 0.59 (Beckman), 0.62 (Siemens), 0.59 (Roche), and 0.59 (Thermo), similar to ROC AUCs achieved with Tg. Combining Tg and TgAb measurements improved the ROC AUCs compared to Tg or TgAb alone. Conclusions: TgAb-IAs show significant qualitative and quantitative differences. For 2 of the 4 TgAb-IAs, using the LOQ improves the detection of interfering TgAbs. All assays showed suboptimal clinical performance when used as surrogate markers of disease, with modest improvements when Tg and TgAb were combined.

May 3, 2017

Thyroglobulin autoantibodies before radioiodine ablation predict differentiated thyroid cancer outcome

Pierpaolo Trimboli, Valentina Zilioli, Mauro Imperiali, Luca Giovanella

Page range: 1995-2001

Abstract

Background: Serum thyroglobulin (Tg) is essential to manage differentiated thyroid carcinoma (DTC). However, Tg determination is affected by circulating Tg antibodies (TgAb), and a role of TgAb as surrogate biomarker has been proposed. Here we evaluated the role of TgAb measured before and after radioiodine ablation (RRA) as potential predictors of prognosis. Methods: Patients treated since 2006 were screened. Cancers with structural relapse were defined as recurrent. Both Tg and TgAb were measured by immunoassays on the fully automated Kryptor ® platform (BRAHMS Gmbh, Henningsdorf, Germany). Results: A series of 215 DTC patients was enrolled, of whom 28.8% had positive preablation TgAb. Overall, 2.8% patients died by DTC and 11% recurred. High-risk class (p=0.004) and cancer relapse (p=0.007) occurred more frequently in positive TgAb, whereas better disease-free survival was observed in negative group (hazard ratio 2.59, p=0.01). Having positive preablation TgAb was significantly associated with risk to develop recurrence (odds ratio 3.57, p=0.004). Among positive TgAb subgroup, higher levels were recorded in recurrent cases (p=0.0001), and the most accurate preablation TgAb threshold was 107.5 IU/mL. When TgAb were measured at first follow-up, recurrence rate was significantly (p<0.0001) higher in persistently TgAb-positive patients (75%) than normalized ones (2.4%). At that time, the highest negative predictive value could be obtained when considering TgAb normalization (<33 IU/mL) or reduction by ≥36.4%. Conclusions: Positive TgAb before RRA indicates higher risk of poor prognosis, but their significant drop 6–12 months later could be considered a favorable factor.

Cardiovascular Diseases

March 22, 2017

Real life dabigatran and metabolite concentrations, focused on inter-patient variability and assay differences in patients with atrial fibrillation

Kristel Boonen, Ellen Schmitz, Fleur Rozestraten, Dennis van den Heuvel, Luc Brunsveld, Pepijn van der Voort, Daan van de Kerkhof

Page range: 2002-2009

Abstract

Background: Dabigatran is prescribed to increasing numbers of patients with atrial fibrillation (AF). Although routine monitoring is not considered to be useful, measuring drug concentrations can be clinically relevant in specific situations. The aim of this study was the comparison of different functional and non-functional assays for determination of dabigatran concentrations at different timepoints in a real-life patient population with AF. We focused on the differences between assays in identifying patients with low drug concentrations. Furthermore, we studied the effect of glucuronidation on the established concentration as determined with different assays. Methods: This study established dabigatran concentration ranges in 40 real-life AF patients by an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) reference method and compared these with results from coagulation assays (Hemoclot dTT, LD-dTT and ECA). Samples were taken just before and 2 and 4 h after taking the drug. Results: A wide range of concentrations at different time points was found in this patient group. Coagulation assays correlate best with UPLC-MS/MS results that include the glucuronidated metabolites, showing that the pharmacologically active glucuronides are also measured in coagulation testing. The LD-dTT has the best agreement with UPLC-MS/MS and combines good sensitivity with high specificity. Several patients show consistently low or high drug concentrations, implying that drug exposure differs between patients. Conclusions: Based on the association of dabigatran concentrations with bleeding and thromboembolic risk, we believe that dabigatran monitoring could be beneficial for further optimizing anticoagulation therapy in AF.

Infectious Diseases

June 24, 2017

HIV avidity index performance using a modified fourth-generation immunoassay to detect recent HIV infections

Barbara Suligoi, Vincenza Regine, Mariangela Raimondo, Anna Rodella, Luigina Terlenghi, Arnaldo Caruso, Patrizia Bagnarelli, Maria Rosaria Capobianchi, Nadia Zanchetta, Valeria Ghisetti, Claudio Galli

Page range: 2010-2019

Abstract

Background: Detecting recent HIV infections is important to evaluate incidence and monitor epidemic trends. We aimed to evaluate the diagnostic performance and accuracy of the avidity index (AI) for discriminating for recent HIV infections. Methods: We collected serum samples from HIV-1 positive individuals: A) with known date of infection (midpoint in time between last HIV-negative and first HIV-positive test); B) infected for >1 year. Samples were divided into two aliquots: one diluted with phosphate buffered saline (PBS) and the other with 1 M guanidine. Both aliquots were assayed by the Architect HIV Ag/Ab Combo 4th generation assay (Abbott). We compared AI found in recent (RI=<6 months from seroconversion) and established (EI) infections. The diagnostic accuracy was evaluated by receiver operating characteristic (ROC) curve analysis. The proportion of samples misclassified as recent (FRR) was calculated. Results: In total, 647 samples were collected: 455 in group A (51.6% RI and 48.4% EI) and 192 in group B. Among these, sixteen samples were from elite controllers, 294 from treated patients, 328 from patients infected with non-B subtypes. Samples before antiretroviral initiation showed a mean AI significantly lower among RI compared to EI (0.66+0.28 vs. 1.00±0.12; p<0.000). The FRR was 0% using a cut-off of ≤0.70. An extremely low FRR was observed among elite controllers, samples with low VL or CD4. HIV subtype had no impact on AI misclassifications. All individuals in group A reached the AI threshold of 0.80 within 24 months after seroconversion. Conclusions: The AI is an accurate serological marker for discriminating recent from established HIV infections and meets WHO requirements for HIV incidence assays.

Letters to the Editor

April 22, 2017

Effect of age on serum prostate-specific antigen in women

Eleftherios P. Diamandis, Emma Eklund, Carla Muytjens, Clare Fiala, Sarah Wheeler, Galina Nikolenko, Anu Mathew, Martin Stengelin, Eli Glezer, Marshall D. Brown, Yingye Zheng, Angelica Lindén Hirschberg

Page range: e271-e272

June 9, 2017

Falsely elevated thyroid-stimulating hormone value due to anti-ruthenium antibodies in a patient with primary hypothyroidism: a case report

Rocío Suarez Rivero, Francisco Ponce Lorenzo, Joaquina Díaz Torres, José Manuel Ruiz Palomar, Domingo Orozco-Beltran

Page range: e273-e275

May 6, 2017

High titers of anti-infliximab antibody do not interfere with Abbott immunoassays

Il Jo, Balázs Szalay, Zsuzsanna Végh, Zsuzsanna Kürti, Ferenc Olajos, Barna Vásárhelyi

Page range: e276-e278

June 23, 2017

Extraordinarily elevated serum CA19-9 in a patient with posterior mediastinum cyst: a case report

Junying Chen, Qianwen Liu, Yihong Ling, Hong Yang, Jing Wen, Kongjia Luo, Yihuai Hu, Zihui Tan, Jianhua Fu

Page range: e279-e281

April 28, 2017

Low levels of 25-OH vitamin D in women with endometriosis and associated pelvic pain

Emanuela Anastasi, Eliana Fuggetta, Corrado De Vito, Giuseppe Migliara, Valentina Viggiani, Lucia Manganaro, Teresa Granato, Pierluigi Benedetti Panici, Antonio Angeloni, Maria Grazia Porpora

Page range: e282-e284

April 28, 2017

Evaluation of serum cortisol biological variation in the evening withdrawal

Ruggero Dittadi, Alessandro Fiorin Damiani, Chiara Olcese

Page range: e285-e287

June 3, 2017

Distinction between urine crystals by automated urine analyzer SediMAX conTRUST is specific but lacks sensitivity

Vincent Castiglione, Etienne Cavalier, Coumba Diop, Romy Gadisseur

Page range: e288-e290

July 14, 2017

Impact of heat-inactivation on anti-Toxoplasma IgM antibody levels

Marie-Pierre Brenier-Pinchart, Hélène Fricker-Hidalgo, Céline Dard, Hervé Pelloux

Page range: e291-e293

About this journal

Objective
Clinical Chemistry and Laboratory Medicine (CCLM) publishes articles on novel teaching and training methods applicable to laboratory medicine. It is focused on basic and applied research and cutting-edge clinical laboratory medicine. CCLM is one of the leading journals in the field, with an impact factor over 8. All contributions submitted for publication in CCLM are single-blind peer reviewed by at least two experts in the field. CCLM is led by a multi-institutional editorial board. It is issued monthly, both in print and electronically. Letters to the Editor and Congress Abstracts are published online only.

Please submit your manuscript here

Topics

clinical biochemistry
clinical genomics and molecular biology
clinical haematology and coagulation
clinical immunology and autoimmunity
clinical microbiology
drug monitoring and analysis
evaluation of diagnostic biomarkers
disease-oriented topics (cardiovascular disease, cancer diagnostics, diabetes)
new reagents, instrumentation and technologies
new methodologies
reference materials and methods
reference values and decision limits
quality and safety in laboratory medicine
translational laboratory medicine
clinical metrology

Article formats
Research Articles, Reviews, Mini Reviews and Opinion Papers on all aspects of clinical chemistry and laboratory medicine, Guidelines and Recommendations, Point/Counterpoint Articles, Letters to the Editor, Editorials

For EFLM Academy Members

To take advantage of all the opportunities offered to members of the EFLM Academy, please access your personal area in the EFLM Academy at the link https://academy.eflm.eu/secretariat/login (if you do not remember your login details, you can use the option FORGOT PASSWORD). Click on the section “International Journals” on the left-hand side where you find CCLM as the first listed journal.

Volume 55 Issue 12

Issue of Clinical Chemistry and Laboratory Medicine (CCLM)

Frontmatter

Tumor microenvironment and systemic disease: a dual target in medical oncology (also in the case of biomarkers)

Sample types applied for molecular diagnosis of therapeutic management of advanced non-small cell lung cancer in the precision medicine

Abstract

The impact of pneumatic tube system on routine laboratory parameters: a systematic review and meta-analysis

Abstract

How to reduce scientific irreproducibility: the 5-year reflection

Abstract

Strategies to define performance specifications in laboratory medicine: 3 years on from the Milan Strategic Conference

Abstract

Intensive educational efforts combined with external quality assessment improve the preanalytical phase in general practitioner offices and nursing homes

Abstract

Separate patient serum sodium medians from males and females provide independent information on analytical bias

Abstract

Are admission procalcitonin levels universal mortality predictors across different medical emergency patient populations? Results from the multi-national, prospective, observational TRIAGE study

Abstract

Biochemical testing in a laboratory tent and semi-intensive care of Ebola patients on-site in a remote part of Guinea: a paradigm shift based on a bleach-sensitive point-of-care device

Abstract

Efficient reporting of the estimated glomerular filtration rate without height in pediatric patients with cancer

Abstract

Evaluation of thyroid test utilization through analysis of population-level data

Abstract

Relation of serum γ-glutamyl transferase activity with copper in an adult population

Abstract

Impact of a single oral dose of 100,000 IU vitamin D3 on profiles of serum 25(OH)D3 and its metabolites 24,25(OH)2D3, 3-epi-25(OH)D3, and 1,25(OH)2D3 in adults with vitamin D insufficiency

Abstract

Automated antinuclear immunofluorescence antibody analysis is a reliable approach in routine clinical laboratories

Abstract

Infrared analyzers for breast milk analysis: fat levels can influence the accuracy of protein measurements

Abstract

A new approach to define acceptance limits for hematology in external quality assessment schemes

Abstract

The effects of transport by car on coagulation tests

Abstract

Combined measurement of factor XIII and D-dimer is helpful for differential diagnosis in patients with suspected pulmonary embolism

Abstract

Influence of age, gender and body mass index on late-night salivary cortisol in healthy adults

Abstract

Assessment of real-time PCR method for detection of EGFR mutation using both supernatant and cell pellet of malignant pleural effusion samples from non-small-cell lung cancer patients

Abstract

Detection of EGFR mutations in patients with non-small cell lung cancer by high resolution melting. Comparison with other methods

Abstract

Predicting outcomes of EGFR-targeted therapy in non-small cell lung cancer patients using pleural effusions samples and peptide nucleic acid probe assay

Abstract

Analytical and clinical performance of thyroglobulin autoantibody assays in thyroid cancer follow-up

Abstract

Thyroglobulin autoantibodies before radioiodine ablation predict differentiated thyroid cancer outcome

Abstract

Real life dabigatran and metabolite concentrations, focused on inter-patient variability and assay differences in patients with atrial fibrillation

Abstract

HIV avidity index performance using a modified fourth-generation immunoassay to detect recent HIV infections

Abstract

Effect of age on serum prostate-specific antigen in women

Falsely elevated thyroid-stimulating hormone value due to anti-ruthenium antibodies in a patient with primary hypothyroidism: a case report

High titers of anti-infliximab antibody do not interfere with Abbott immunoassays

Extraordinarily elevated serum CA19-9 in a patient with posterior mediastinum cyst: a case report

Low levels of 25-OH vitamin D in women with endometriosis and associated pelvic pain

Evaluation of serum cortisol biological variation in the evening withdrawal

Distinction between urine crystals by automated urine analyzer SediMAX conTRUST is specific but lacks sensitivity

Impact of heat-inactivation on anti-Toxoplasma IgM antibody levels

Impact of a single oral dose of 100,000 IU vitamin D3 on profiles of serum 25(OH)D3 and its metabolites 24,25(OH)₂D3, 3-epi-25(OH)D3, and 1,25(OH)₂D3 in adults with vitamin D insufficiency