Clinical laboratory characteristics and gene mutation spectrum of Ph-negative MPN patients with atypical variants of JAK2, MPL, or CALR.

OBJECTIVE: To evaluate the incidence, clinical laboratory characteristics, and gene mutation spectrum of Ph-negative MPN patients with atypical variants of JAK2, MPL, or CALR. METHODS: We collected a total of 359 Ph-negative MPN patients with classical mutations in driver genes JAK2, MPL, or CALR, and divided them into two groups based on whether they had additional atypical variants of driver genes JAK2, MPL, or CALR: 304 patients without atypical variants of driver genes and 55 patients with atypical variants of driver genes. We analyzed the relevant characteristics of these patients. RESULTS: This study included 359 patients with Ph-negative MPNs with JAK2, MPL, or CALR classical mutations and found that 55 (15%) patients had atypical variants of JAK2, MPL, or CALR. Among them, 28 cases (51%) were male, and 27 (49%) were female, with a median age of 64 years (range, 21-83). The age of ET patients with atypical variants was higher than that of ET patients without atypical variants [70 (28-80) vs. 61 (19-82), p = 0.03]. The incidence of classical MPL mutations in ET patients with atypical variants was higher than in ET patients without atypical variants [13.3% (2/15) vs. 0% (0/95), p = 0.02]. The number of gene mutations in patients with atypical variants of driver genes PV, ET, and Overt-PMF is more than in patients without atypical variants of PV, ET, and Overt-PMF [PV: 3 (2-6) vs. 2 (1-7), p < 0.001; ET: 4 (2-8) vs. 2 (1-7), p < 0.05; Overt-PMF: 5 (2-9) vs. 3 (1-8), p < 0.001]. The incidence of SH2B3 and ASXL1 mutations were higher in MPN patients with atypical variants than in those without atypical variants (SH2B3: 16% vs. 6%, p < 0.01; ASXL1: 24% vs. 13%, p < 0.05). CONCLUSION: These data indicate that classical mutations of JAK2, MPL, and CALR may not be completely mutually exclusive with atypical variants of JAK2, MPL, and CALR. In this study, 30 different atypical variants of JAK2, MPL, and CALR were identified, JAK2 G127D being the most common (42%, 23/55). Interestingly, JAK2 G127D only co-occurred with JAK2V617F mutation. The incidence of atypical variants of JAK2 in Ph-negative MPNs was much higher than that of the atypical variants of MPL and CALR. The significance of these atypical variants will be further studied in the future.

Laboratory Data Timeliness and Completeness Improves Following Implementation of an Electronic Laboratory Information System in Côte d'Ivoire: Quasi-Experimental Study on 21 Clinical Laboratories From 2014 to 2020.

BACKGROUND: The Ministry of Health in Côte d'Ivoire and the International Training and Education Center for Health at the University of Washington, funded by the United States President's Emergency Plan for AIDS Relief, have been collaborating to develop and implement the Open-Source Enterprise-Level Laboratory Information System (OpenELIS). The system is designed to improve HIV-related laboratory data management and strengthen quality management and capacity at clinical laboratories across the nation. OBJECTIVE: This evaluation aimed to quantify the effects of implementing OpenELIS on data quality for laboratory tests related to HIV care and treatment. METHODS: This evaluation used a quasi-experimental design to perform an interrupted time-series analysis to estimate the changes in the level and slope of 3 data quality indicators (timeliness, completeness, and validity) after OpenELIS implementation. We collected paper and electronic records on clusters of differentiation 4 (CD4) testing for 48 weeks before OpenELIS adoption until 72 weeks after. Data collection took place at 21 laboratories in 13 health regions that started using OpenELIS between 2014 and 2020. We analyzed the data at the laboratory level. We estimated odds ratios (ORs) by comparing the observed outcomes with modeled counterfactual ones when the laboratories did not adopt OpenELIS. RESULTS: There was an immediate 5-fold increase in timeliness (OR 5.27, 95% CI 4.33-6.41; P<.001) and an immediate 3.6-fold increase in completeness (OR 3.59, 95% CI 2.40-5.37; P<.001). These immediate improvements were observed starting after OpenELIS installation and then maintained until 72 weeks after OpenELIS adoption. The weekly improvement in the postimplementation trend of completeness was significant (OR 1.03, 95% CI 1.02-1.05; P<.001). The improvement in validity was not statistically significant (OR 1.34, 95% CI 0.69-2.60; P=.38), but validity did not fall below pre-OpenELIS levels. CONCLUSIONS: These results demonstrate the value of electronic laboratory information systems in improving laboratory data quality and supporting evidence-based decision-making in health care. These findings highlight the importance of OpenELIS in Côte d'Ivoire and the potential for adoption in other low- and middle-income countries with similar health systems.

Lung cancer tumor marker analysis: A clinical laboratory perspective.

 Clinical laboratories are responsible for performing lung cancer tumor marker testing as part of routine clinical care. It is their responsibility to guarantee that the reported tumor marker results are reliable and meet the necessary quality standards for proper clinical use. During the different laboratory phases, pre-analytical, analytical and post-analytical, specific steps and processes can introduce errors and generate incorrect clinical interpretation. This editorial briefly outlines critical laboratory issues related to lung cancer tumor markers, specific for each of these three laboratory phases.

Dissociation Phenomenon of Erythrocyte Agglutination and Its Application to Assay of Functional Activity of the Complement System in Clinical Laboratory.

OBJECTIVE: The objective of the study was to validate the dissociation phenomenon of erythrocyte agglutination which is based on erythrocyte fragments and to apply it in the functional activity assay of the complement system. METHODS: The dissociation-agglutination effect of erythrocyte fragments was validated by detecting the number of free erythrocytes after the action of erythrocyte fragments on agglutinated erythrocytes. The number of free erythrocytes produced after hemolysis of agglutinated erythrocytes caused by complements and complement activators(CAs) was detected by auto hematology analyzer and the results were indicated by mean hemoglobin concentration of erythrocytes (MCHC). We optimized the test conditions and validated the inter-batch stability, explored the resolution of the assay method, and assayed for the total complement activity (AC) and the CAs activated complement activity (ACA) in serum from patients and healthy individual groups. RESULTS: Erythrocyte fragments have a dissociative effect on agglutinated erythrocytes. The auto hematology analyzer was able to detect AC and ACA, where AC showed an inverse correlation with MCHC, and ACA demonstrated a positive correlation with MCHC. The inter-batch CV of AC, ACA, and ACA/AC was found to be 5%, 9%, and 11.7%, respectively, with good stability. The study found that serum samples from acute phase reaction patients showed significant differences in ACA compared with healthy individuals, with a p value of 0.018; serum samples from patients with nephrotic syndrome showed significant differences in AC, ACA, and ACA/AC compared with healthy individuals, with p values of 0.014, 0.002, and 0.041, respectively. CONCLUSION: Erythrocyte fragments have dissociation-agglutination effect. The complement system immunological functional detection method, based on this effect, has potential clinical application value due to its sensitivity and accuracy.

Insights from semi-structured interviews on integrating artificial intelligence in clinical chemistry laboratory practices.

BACKGROUND: Artificial intelligence (AI) is gradually transforming the practises of healthcare providers. Over the last two decades, the advent of AI into numerous aspects of pathology has opened transformative possibilities in how we practise laboratory medicine. Objectives of this study were to explore how AI could impact the clinical practices of professionals working in Clinical Chemistry laboratories, while also identifying effective strategies in medical education to facilitate the required changes. METHODS: From March to August 2022, an exploratory qualitative study was conducted at the Section of Clinical Chemistry, Department of Pathology and Laboratory Medicine, Aga Khan University, Karachi, Pakistan, in collaboration with Keele University, Newcastle, United Kingdom. Semi-structured interviews were conducted to collect information from diverse group of professionals working in Clinical Chemistry laboratories. All interviews were audio recorded and transcribed verbatim. They were asked what changes AI would involve in the laboratory, what resources would be necessary, and how medical education would assist them in adapting to the change. A content analysis was conducted, resulting in the development of codes and themes based on the analyzed data. RESULTS: The interviews were analysed to identify three primary themes: perspectives and considerations for AI adoption, educational and curriculum adjustments, and implementation techniques. Although the use of diagnostic algorithms is currently limited in Pakistani Clinical Chemistry laboratories, the application of AI is expanding. All thirteen participants stated their reasons for being hesitant to use AI. Participants stressed the importance of critical aspects for effective AI deployment, the need of a collaborative integrative approach, and the need for constant horizon scanning to keep up with AI developments. CONCLUSIONS: Three primary themes related to AI adoption were identified: perspectives and considerations, educational and curriculum adjustments, and implementation techniques. The study's findings give a sound foundation for making suggestions to clinical laboratories, scientific bodies, and national and international Clinical Chemistry and laboratory medicine organisations on how to manage pathologists' shifting practises because of AI.

Proceedings of the Clinical Microbiology Open 2022-assessing clinical laboratory and industry responses to COVID-19 pandemic testing capacity challenges (part 1).

As the COVID-19 pandemic winds down, clinical and public health laboratories, along with industry partners, reflect on the successes and failures of the pandemic response. To capture the lessons learned and better prepare for the next pandemic, the Clinical Microbiology Open (CMO) assembled key stakeholders including directors of clinical laboratories, industry partners, and state and federal agencies such as the Centers for Disease Control and Prevention and the Food and Drug Administration. Participants were asked to provide their perspectives on the initial pandemic response, supply chain constraints especially during surges, staffing challenges, test triage and communication strategies, clinical informatics needs, laboratory financial impacts of SARS-CoV-2 testing, and the emergency use authorization process. This manuscript summarizes the diagnostic laboratory and industry perspectives on these issues that were presented and discussed at CMO and proposes some steps that could be taken to improve future pandemic responses.

Development and validation of a prognostic model based on clinical laboratory biomarkers to predict admission to ICU in Omicron variant-infected hospitalized patients complicated with myocardial injury.

Aims: The aim of this study was to develop and validate a prognostic model based on clinical laboratory biomarkers for the early identification of high-risk patients who require intensive care unit (ICU) admission among those hospitalized with the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and complicated with myocardial injury (MI). Methods: This single-center study enrolled 263 hospitalized patients with confirmed Omicron variant infection and concurrent MI. The patients were randomly divided into training and validation cohorts. Relevant variables were collected upon admission, and the least absolute shrinkage and selection operator (LASSO) was used to select candidate variables for constructing a Cox regression prognostic model. The model's performance was evaluated in both training and validating cohorts based on discrimination, calibration, and net benefit. Results: Of the 263 eligible patients, 210 were non-ICU patients and 53 were ICU patients. The prognostic model was built using four selected predictors: white blood cell (WBC) count, procalcitonin (PCT) level, C-reactive protein (CRP) level, and blood urea nitrogen (BUN) level. The model showed good discriminative ability in both the training cohort (concordance index: 0.802, 95% CI: 0.716-0.888) and the validation cohort (concordance index: 0.799, 95% CI: 0.681-0.917). For calibration, the predicted probabilities and observed proportions were highly consistent, indicating the model's reliability in predicting outcomes. In the 21-day decision curve analysis, the model had a positive net benefit for threshold probability ranges of 0.2 to 0.8 in the training cohort and nearly 0.2 to 1 in the validation cohort. Conclusion: In this study, we developed a clinically practical model with high discrimination, calibration, and net benefit. It may help to early identify severe and critical cases among Omicron variant-infected hospitalized patients with MI.

A call-to-action for energy conservation and sustainability in the clinical laboratory: Experiences from the University of Padova.

OBJECTIVES: Healthcare has a considerable environmental impact, yet it has been largely overlooked. Clinical laboratories, in particular, consume significantly more energy and water per unit area compared to standard office buildings. It is crucial to raise awareness among laboratories about the significance of embracing eco-friendly practices. Numerous energy-saving measures do not incur additional costs but necessitate a shift in organizational culture and mindset. DESIGN & METHODS: This paper conducts a cost-benefit analysis of energy consumption at the Laboratory Medicine Unit of University Hospital of Padova, beginning with laboratory refrigerators and freezers. RESULTS: The need to rationalize the existing units, especially the combined refrigerators-freezers, and reorganize the contents of the Ultra-Low Temperature freezers with an energy-saving perspective has emerged. CONCLUSIONS: By implementing these practices, this initiative can gradually expand to encompass more green activities in the future.

Effects of reverse osmosis membrane replacement of pure water system on clinical chemistry and immunoassay in clinical laboratory.

Introduction: Reverse osmosis (RO) membrane, key component of water-purifying equipment, is often stored in protection fluid containing substances such as glycerol, which may contaminate the water at replacement. This study aims to explore the effects of RO membrane replacement on clinical chemistry and immunoassay, particularly triglyceride (TG), providing reference for managing test interference caused by RO membrane replacement. Materials and methods: The RO membrane of water-purifying equipment A, which provided water to C16000 biochemistry analyzer (Abbott Laboratories, Abbott Park, USA) and E801 electrochemiluminescence analyzer (Roche, Basel, Switzerland), was replaced. Water resistivity was recorded, and quality control (QC) tests were performed on C16000 and E801. Moreover, TG was measured in 29 of selected serum samples on C16000 at 0.5h and 10.5h after RO membrane replacement and on reference biochemistry analyzer BS2000M (Mindray Biomedical Electronics Co., Shenzhen, China), which was connected to water-purifying equipment B without RO membrane replacement. Finally, blank, calibrator 1 and calibrator 2 of TG reagent were measured on C16000 before and at 0.5h, 2.5h and 10.5h after RO membrane replacement. All statistical analyses of data were done using GraphPad Prism (GraphPad Software Inc., San Diego, USA), and a value of P < 0.05 was considered statistically significant. Results: After RO membrane replacement, all QC results of clinical chemistry and immune tests passed except TG that showed positive bias of 536% and 371% at two levels, respectively. Moreover, TG results of the same serum samples were significantly higher at 0.5h than 10.5h after RO membrane replacement. Meanwhile, there was worse agreement and correlation of TG results between C16000 and BS2000M at 0.5h than 10.5h after replacement. Furthermore, the absorbance of TG blank, calibrator 1 and calibrator 2 was significantly higher at 0.5h and 2.5h after replacement than before replacement, and the absorbance gradually returned to normal value at 10.5h after replacement. Conclusions: Replacement of RO membrane could cause significant interference to TG test while have no effects on other laboratory tests performed in the study, which may be due to glycerol contamination. Our data provides important reference for management of test interference caused by RO membrane replacement. Clinical laboratory should observe the effects of RO membrane replacement on laboratory tests through both water quality monitoring and QC detection.

Screening for Colorectal Cancer: The Role of Clinical Laboratories.

BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer incidence and mortality. Screening can result in reductions in incidence and mortality, but there are many challenges to uptake and follow-up. CONTENT: Here, we will review the changing epidemiology of CRC, including increasing trends for early and later onset CRC; evidence to support current and emerging screening strategies, including noninvasive stool and blood-based tests; key challenges to ensuring uptake and high-quality screening; and the critical role that clinical laboratories can have in supporting health system and public health efforts to reduce the burden of CRC on the population. SUMMARY: Clinical laboratories have the opportunity to play a seminal role in optimizing early detection and prevention of CRC.

Taking Center Stage: Clinical Laboratory Leading Diagnostic Stewardship Efforts.

This article will discuss diagnostic stewardship from the perspective of those who are just starting, or have recently started, a diagnostic stewardship effort. This document will provide guidance on how to identify opportunities for intervention and tools that can be used to affect change. Specifically, we will discuss key components of a diagnostic stewardship committee, referral laboratory testing, prior authorization, miscellaneous test orders, establishing a laboratory test formulary, and conclude with some specific examples of interventions that can be considered.

Home and Clinical Laboratory Improvement Amendments-Waived Testing for Infectious Diseases-How Do These Fit in the Testing Landscape?

Though testing for infectious diseases has long been performed in traditional clincial laboratory settings, more widespread availability of waived testing is expanding accessibility of patients to rapid test results. This is being further expanded to home testing. Nevertheless, with this greater democratization and availability of clinical testing there are important limitations that need to be balanced. In this article, we review the current test landscape for infectious diseases waived testing and opportunities for assuring optimal quality testing.

ICSH guidance for internal quality control policy for blood cell counters.

This paper is a description of the ICSH guidance for internal quality control (IQC) policy for blood cell counters. It follows from and links to a separate ICSH review for such policies and practices. The ICSH has gathered information regarding the current state of practice through review of published guidance from regulatory bodies, a questionnaire to six major cell counter manufacturers and a survey issued to 191 diagnostic laboratories in four countries (China, the Republic of Ireland, Spain, and the United Kingdom) on their IQC practice and approach to the use of commercial IQC materials. This has revealed diversity both in guidance and in practice around the world. There is diversity in guidance from regulatory organizations in regard to IQC methods each recommends, clinical levels to use and frequency to run commercial controls, and finally recommended sources of commercial control materials. The diversity in practice among clinical laboratories spans the areas of IQC methods used, derivation of target values, and action limits used with commercial control materials, and frequency of running commercial controls materials. These findings and their implications for IQC Practice are addressed in this guidance document, which proposes a harmonized approach to address the issues faced by diagnostic laboratories.

Defining allowable total error limits in the clinical laboratory.

Allowable total error (ATE) are performance specification limits predefined for a variety of laboratory analytes. These limits define the maximum amount of error that is allowed for an assay when judging acceptability of a new assay during method verification/validation, evaluating patient or instrument comparison data, or in designing a quality control strategy. There are several widely available resources and models that can serve as a guide in selecting ATE. They may be based on legal requirements or set by providers of proficiency testing (PT) and external quality assessment schemes (EQAS). ATE can be also determined by professional expert groups or be based on biological variation of an analyte. Because there are several resources to choose from, there have been several attempts in reaching consensus on which ATE resource should be given preference. This chapter reviews several of these resources in more detail and discusses the difference between allowable total error (ATE) and observed total analytical error (TAE).

Blood culture quality and turnaround time of clinical microbiology laboratories in Chinese Teaching Hospitals: A multicenter study.

PURPOSE: Blood culture (BC) remains the gold standard for the diagnosis of bloodstream infections. Improving the quality of clinical BC samples, optimizing BC performance, and accelerating antimicrobial susceptibility test (AST) results are essential for the early detection of bloodstream infections and specific treatments. METHODS: We conducted a retrospective multicenter study using 450,845 BC specimens from clinical laboratories obtained from 19 teaching hospitals between 1 January 2021 and 31 December 2021. We evaluated key performance indicators (KPIs), turnaround times (TATs), and frequency distributions of processing in BC specimens. We also evaluated the AST results of clinically significant isolates for four different laboratory workflow styles. RESULTS: Across the 10 common bacterial isolates (n = 16,865) and yeast isolates (n = 1011), the overall median (interquartile range) TATs of AST results were 2.67 (2.05-3.31) and 3.73 (2.98-4.64) days, respectively. The specimen collections mainly occurred between 06:00 and 24:00, and specimen reception and loadings mainly between 08:00 and 24:00. Based on the laboratory workflows of the BCs, 16 of the 19 hospitals were divided into four groups. Time to results (TTRs) from specimen collection to the AST reports were 2.35 (1.95-3.06), 2.61 (1.98-3.32), 2.99 (2.60-3.87), and 3.25 (2.80-3.98) days for groups I, II, III, and IV, respectively. CONCLUSION: This study shows the related BC KPIs and workflows in different Chinese hospitals, suggesting that laboratory workflow optimization can play important roles in shortening time to AST reports and initiation of appropriate timely treatment.

Exploration of useful clinical laboratory values as diagnostic criteria for eosinophilic gastroenteritis.

BACKGROUND: Eosinophilic gastroenteritis (EGE) is a rare eosinophilic infiltrative disorder. In Japan, EGE is diagnosed using clinical symptoms as well as microscopic, haematologic and histopathological findings. In this study, we examined the usefulness of laboratory data in the diagnosis of EGE. METHODS: Patients who were diagnosed with EGE at Fujita Health University Bantane Hospital between April 2015 and December 2020 were enrolled in this study and their data was retrospectively analysed. We evaluated their medical history, laboratory data including leukocyte count, eosinophil count, immunoglobulin (Ig) E, thymus and activation-regulated chemokine (TARC), C-reactive protein (CRP), etc. and histopathological data were collected from the electronic medical records. RESULTS: One hundred twelve of 168 patients who were treated for EGE could be analysed. The peripheral eosinophil count was correlated with the duodenal or ascending colon eosinophil count; moreover, the blood lymphocyte count and the TARC were correlated with the transverse colon eosinophil count. Multivariate regression analysis showed correlations only in the oesophagus, stomach and duodenum. Specifically, correlations were noted between blood eosinophils and gastric eosinophils, blood eosinophils and duodenal eosinophils, blood lymphocytes and gastric eosinophils, blood IgE and oesophageal, gastric and duodenal eosinophils and CRP and oesophageal eosinophils. CONCLUSION: The extent of blood eosinophil count, lymphocyte count, IgE and CRP elevation together with clinical features and pathology can be incorporated into a diagnostic scoring criteria system to improve the accuracy of diagnosing this uncommon condition in the future.

Clinical Laboratory Investigations and Antivenom Administration after Malayan Pit Viper (Calloselasma rhodostoma) Envenoming: A Retrospective Study from Southernmost Thailand.

The Malayan pit viper (MPV: Calloselasma rhodostoma) is a medically important venomous snake causing numerous envenomations in Thailand. Administration of specific snake antivenom is the only effective treatment for MPV-envenomed patients. However, inappropriate administration or misuse of snake antivenom is problematic in some remote areas of tropical countries where the snakebite envenoming rate is notable. Currently, the indications for administration of MPV antivenom are focused mainly on hematological factors. These include 1) venous clotting time > 20 min, 2) unclotted 20-minute whole-blood clotting time, 3) international normalized ratio > 1.2, 4) platelet count < 50 × 103/µL, 5) systemic bleeding, and 6) impending compartment syndrome. We aimed to determine the association between laboratory data and antivenom administration in MPV-envenomed patients. A retrospective study of data from 2016 to 2021 in Narathiwat Province, the southernmost province in Thailand, was conducted. A total of 838 MPV-bitten patients were included in this study. Local effects and systemic effects were observed in 58.8% and 27.7% of patients, respectively. Coagulopathies, which range from abnormal blood clotting to systemic bleeding, represented the majority of systemic effects. Acute kidney injury developed in 2.5% of patients. In this study, 57.3% of patients were considered appropriate antivenom recipients. Interestingly, the present study revealed that local bleeding and mild to moderate thrombocytopenia became the independent factors for inappropriate use of MPV antivenom. Reeducation and supervision regarding the rational use of snake antivenom are needed to minimize the misuse of antivenom.

Are analytical performance specifications derived from reference intervals of any use in the veterinary clinical laboratory? A preliminary study on the empirical biological variation model.

BACKGROUND: Analytical performance specifications (APS) are vital for method evaluation and quality control validation. However, the limited availability of biological variation (BV) data, regulatory guidelines, and expert opinion (EO) may present challenges in veterinary medicine. The empirical biological variation (EBV) approach, based on population reference intervals (pRI), has emerged as an alternative method to derive APS in human medicine. OBJECTIVES: This study aimed to assess the practicality and usefulness of the EBV approach in deriving performance limits for various measurands in dogs and cats. METHODS: Eight hematology and 13 biochemistry measurands were analyzed in dogs and cats. Estimates of combined biologic variation based on traditional biological (CVB ) and EBV-derived (CVE *) formulas were calculated and assessed for evidence of correlation. Performance limits for expanded uncertainty/total error and imprecision were compared among EO, BV, and EBV. RESULTS: Strong and significant correlations were found between CVB and CVE * for both dogs (r = .86, p < .00001) and cats (r = 0.95, p < .00001). The EBV-derived APS were generally comparable to EO and BV, with a subjective criterion of 1.5% difference for imprecision and 3% for total error/expanded uncertainty. CONCLUSION: The EBV approach, using pRI, shows promise as a surrogate marker for biological variation and as a practical tool for determining performance limits in dogs and cats. Assuming accurate pRI generated on analyzers with stable analytical performance, this approach could offer benefits when expert recommendations or robust BV studies are lacking or yield conflicting results. Further research is needed to explore the applicability and advantages of the EBV in veterinary medicine.