center dot Context.-Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) assay reagents are available both with and without supplementation with pyridoxal-5'-phosphate (P5P; the active form of vitamin B6), a catalytic cofactor required for their enzymatic reactions. Nonsupplemented assays may miss ALT or AST elevations in patients with vitamin B6 deficiency. Objective.-To assess awareness and adoption of ALT and AST reagents that are supplemented with P5P. Design.-A 4-question survey about ALT and AST reagent supplementation with P5P was included in the College of American Pathologists General Chemistry and Therapeutic Drugs (C program) proficiency testing 2023 B mailing. Results.-Overall, 38% (1651 of 4304) of responding laboratories reported using ALT and/or AST reagent supplemented with P5P. P5P supplementation was more common for nonacademic hospital/medical center laboratories (44%; 713 of 1629) relative to other settings. Of the laboratories that reported not using P5P-supplemented reagents, few (5%; 141 of 2611) cited plans to convert in the future. Despite the availability of P5P-supplemented reagents from several major assay manufacturers, the most common stated barrier for adoption was that the laboratory's reagent manufacturer does not provide P5P-supplemented reagents. Conclusions.-There is a lack of awareness of the existence and benefits of P5P-supplemented ALT and AST reagents. There is a need for ALT and AST assay manufacturers to clarify and standardize the P5P status of ALT and AST reagents. (Arch Pathol Lab Med. 2025;149:400-404; doi: 10.5858/ arpa.2024-0097-CP)

Context.— Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) assay reagents are available both with and without supplementation with pyridoxal-5’-phosphate (P5P; the active form of vitamin B6), a catalytic cofactor required for their enzymatic reactions. Nonsupplemented assays may miss ALT or AST elevations in patients with vitamin B6 deficiency. Objective.— To assess awareness and adoption of ALT and AST reagents that are supplemented with P5P. Design.— A 4-question survey about ALT and AST reagent supplementation with P5P was included in the College of American Pathologists General Chemistry and Therapeutic Drugs (C program) proficiency testing 2023 B mailing. Results.— Overall, 38% (1651 of 4304) of responding laboratories reported using ALT and/or AST reagent supplemented with P5P. P5P supplementation was more common for nonacademic hospital/medical center laboratories (44%; 713 of 1629) relative to other settings. Of the laboratories that reported not using P5P-supplemented reagents, few (5%; 141 of 2611) cited plans to convert in the future. Despite the availability of P5P-supplemented reagents from several major assay manufacturers, the most common stated barrier for adoption was that the laboratory’s reagent manufacturer does not provide P5P-supplemented reagents. Conclusions.— There is a lack of awareness of the existence and benefits of P5P-supplemented ALT and AST reagents. There is a need for ALT and AST assay manufacturers to clarify and standardize the P5P status of ALT and AST reagents.

Sepsis, a dysregulated host immune response to an infectious agent, significantly increases morbidity and mortality for hospitalized patients worldwide. This chapter reviews (1) the basic principles of infectious diseases, pathophysiology and current definition of sepsis, (2) established sepsis biomarkers such lactate, procalcitonin and C-reactive protein, (3) novel, newly regulatory-cleared/approved biomarkers, such as assays that evaluate white blood cell properties and immune response molecules, and (4) emerging biomarkers and biomarker panels to highlight future directions and opportunities in the diagnosis and management of sepsis.

There is a close relationship between the goals of laboratory stewardship and efforts to improve health equity for vulnerable populations. Laboratory stewardship programs should evaluate their policies and interventions to ensure that they improve access to testing, test selection, and result interpretation and delivery for all populations. Specific solutions to consider are (1) to evaluate the benefits of point-of-care testing when it can decrease barriers to specimen collection, (2) to use standardized naming conventions to help providers select the best test, and (3) to partner with insurance processing departments to help reduce financial barriers for expensive testing.

BACKGROUND:Procalcitonin (PCT), a peptide precursor of the hormone calcitonin, is a biomarker whose serum concentrations are elevated in response to systemic inflammation caused by bacterial infection and sepsis. Clinical adoption of PCT in the United States has only recently gained traction with an increasing number of Food and Drug Administration-approved assays and expanded indications for use. There is interest in the use of PCT as an outcomes predictor as well as an antibiotic stewardship tool. However, PCT has limitations in specificity, and conclusions surrounding its utility have been mixed. Further, there is a lack of consensus regarding appropriate timing of measurements and interpretation of results. There is also a lack of method harmonization for PCT assays, and questions remain regarding whether the same clinical decision points may be used across different methods.CONTENT:This guidance document aims to address key questions related to the use of PCT to manage adult, pediatric, and neonatal patients with suspected sepsis and/or bacterial infections, particularly respiratory infections. The document explores the evidence for PCT utility for antimicrobial therapy decisions and outcomes prediction. Additionally, the document discusses analytical and preanalytical considerations for PCT analysis and confounding factors that may affect the interpretation of PCT results.SUMMARY:While PCT has been studied widely in various clinical settings, there is considerable variability in study designs and study populations. Evidence to support the use of PCT to guide antibiotic cessation is compelling in the critically ill and in some lower respiratory tract infections but is lacking in other clinical scenarios, and evidence is also limited in the pediatric and neonatal populations. Interpretation of PCT results requires guidance from multidisciplinary care teams of clinicians, pharmacists, and clinical laboratorians.

Objectives:We sought to identify immune biomarkers associated with severe Coronavirus disease 2019 (COVID-19) in patients admitted to a large urban hospital during the early phase of the SARS-CoV-2 pandemic. Design:The study population consisted of SARS-CoV-2 positive subjects admitted for COVID-19 (n = 58) or controls (n = 14) at the Los Angeles County University of Southern California Medical Center between April 2020 through December 2020. Immunologic markers including chemokine/cytokines (IL-6, IL-8, IL-10, IP-10, MCP-1, TNF-α) and serologic markers against SARS-CoV-2 antigens (including spike subunits S1 and S2, receptor binding domain, and nucleocapsid) were assessed in serum collected on the day of admission using bead-based multiplex immunoassay panels. Results:We observed that body mass index (BMI) and SARS-CoV-2 antibodies were significantly elevated in patients with the highest COVID-19 disease severity. IP-10 was significantly elevated in COVID-19 patients and was associated with increased SARS-CoV-2 antibodies. Interactions among all available variables on COVID-19 disease severity were explored using a linear support vector machine model which supported the importance of BMI and SARS-CoV-2 antibodies. Conclusions:Our results confirm the known adverse association of BMI on COVID-19 severity and suggest that IP-10 and SARS-CoV-2 antibodies could be useful to identify patients most likely to experience the most severe forms of the disease.

BACKGROUND:Many states in the United States have progressed towards legalization of marijuana including decriminalization, medicinal and/or recreational use. We studied the impact of legalization on cannabis-related emergency department visits in states with varying degrees of legalization.METHODS:Seventeen healthcare institutions in fifteen states (California, Colorado, Connecticut, Florida, Iowa, Kentucky, Maryland, Massachusetts, Missouri, New Hampshire, Oregon, South Carolina, Tennessee, Texas, Washington) participated. Cannabinoid immunoassay results and cannabis-related International Classification of Diseases (ninth and tenth versions) codes were obtained for emergency department visits over a 3- to 8-year period during various stages of legalization: no state laws, decriminalized, medical approval before dispensaries, medical dispensaries available, recreational approval before dispensaries and recreational dispensaries available. Trends and monthly rates of cannabinoid immunoassay and cannabis-related International Classification of Diseases code positivity were determined during these legalization periods.RESULTS:For most states, there was a significant increase in both cannabinoid immunoassay and International Classification of Diseases code positivity as legalization progressed; however, positivity rates differed. The availability of dispensaries may impact positivity in states with medical and/or recreational approval. In most states with no laws, there was a significant but smaller increase in cannabinoid immunoassay positivity rates.CONCLUSIONS:States may experience an increase in cannabis-related emergency department visits with progression toward marijuana legalization. The differences between states, including those in which no impact was seen, are likely multifactorial and include cultural norms, attitudes of local law enforcement, differing patient populations, legalization in surrounding states, availability of dispensaries, various ordering protocols in the emergency department, and the prevalence of non-regulated cannabis products.

BACKGROUND In the United States, federal regulations under CLIA '88 require reportable range verification of quantitative assays used for clinical purposes. Some accreditation agencies and other standards development organizations have their own additional requirements, recommendations, and/or terminologies relating to reportable range verification, leading to varying practices among clinical laboratories. CONTENT Requirements and recommendations related to reportable range or analytical measurement range verification from different organizations are reviewed and compared. Optimal approaches to materials selection, data analysis, and troubleshooting are collated. SUMMARY This review clarifies key concepts and outlines various practical approaches to reportable range verification.

OBJECTIVES:. The objective of this study was to compare the temporal dynamics of two viral-induced inflammatory proteins interferon gamma inducible protein-10 (IP-10) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), as well as C-reactive protein (CRP) among patients hospitalized for COVID-19 and examine their prognostic significance. DESIGN:. Prospective observational cohort study. SETTING:. Multicenter, inpatient. PATIENTS:. Adult patients infected with severe acute respiratory syndrome coronavirus 2 between March 2021 and October 2021. INTERVENTIONS:. Patient sera were collected on days 1, 3, 5, and 7 of hospitalization. Levels of IP-10, TRAIL, and CRP were measured using a point-of-need diagnostic immunoassay platform (MeMed BV, MeMed, Haifa, Israel) and compared between patients grouped by disease severity (severe vs nonsevere). MEASUREMENTS AND MAIN RESULTS:. Baseline characteristics were similar regardless of severity except for a higher prevalence of diabetes and heart failure among severe patients. The immune profile at admission was similar between groups; IP-10 and CRP levels generally decreased while TRAIL levels increased over time in all patients. However, the severe group had higher IP-10 (median 713 vs 328 pg/mL; p = 0.045) and lower TRAIL levels (median 21 vs 30 pg/mL; p = 0.003) on day 3 compared with nonsevere patients. A breakpoint IP-10 level of greater than or equal to 570 pg/mL and TRAIL level of less than 25 pg/mL on day 3 were associated with COVID-19 severity. Patients with elevated day 3 IP-10 levels (≥ 570 pg/mL) were more likely to experience prolonged recovery time (median 12 vs 3 d; p < 0.001). The severe group had prolonged use of corticosteroids (12 vs 5 d; p < 0.001) and had a higher rate of secondary infections (20% vs 6%; p = 0.04) and in-hospital mortality (20% vs 0%; p < 0.001) as compared with nonsevere patients. CONCLUSIONS:. The observed patterns in host immune response revealed a turning point in COVID-19 disease on hospital day 3 and the potential utility of IP-10 and TRAIL as sensitive markers associated with disease severity and time to recovery.

This study includes clinical laboratories that participated in the first general chemistry proficiency testing survey in 2022 to assess awareness and adoption of new equations from the Chronic Kidney Disease Epidemiology Collaboration for estimated glomerular filtration rate (eGFR) that eliminated race-adjustment factors, including one based on creatinine and one based on creatinine and cystatin C.

Background Commonly used estimated glomerular filtration rate (eGFR) equations include a Black race modifier (BRM) that was incorporated during equation derivation. Race is a social construct, and a poorly characterized variable that is applied inconsistently in clinical settings. The BRM results in higher eGFR for any creatinine concentration, implying fundamental differences in creatinine production or excretion in Black individuals compared to other populations. Equations without inclusion of the BRM have the potential to detect kidney disease earlier in patients at the greatest risk of chronic kidney disease (CKD), but also has the potential to over-diagnose CKD or impact downstream clinical interventions. The purpose of this study was to use an evidence-based approach to systematically evaluate the literature relevant to the performance of the eGFR equations with and without the BRM and to examine the clinical impact of the use or removal. Content PubMed and Embase databases were searched for studies comparing measured GFR to eGFR in racially diverse adult populations using the Modification of Diet in Renal Disease or the 2009-Chronic Kidney Disease Epidemiology Collaboration-creatinine equations based on standardized creatinine measurements. Additionally, we searched for studies comparing clinical use of eGFR calculated with and without the BRM. Here, 8632 unique publications were identified; an additional 3 studies were added post hoc. In total, 96 studies were subjected to further analysis and 44 studies were used to make a final assessment. There is limited published evidence to support the use of a BRM in eGFR equations.

Introduction: Acute pancreatitis (AP) is a leading indication for hospital admission. The relationship between AP and diabetes mellitus (DM) is becoming increasingly recognized. Many patients with DM have comorbid conditions (ex. heart and renal disease) that may increase the risk of severe pancreatitis or pancreatitis outcomes. We aim to identify the impact of DM on acute pancreatitis hospital outcomes including organ failure, readmission, and death. Methods: We identified patients hospitalized for acute pancreatitis between January 2015 and March 2021 using our prospective observational cohort. We included patients who had an episode of acute pancreatitis with or without pre-existing DM. Outcomes of interest included severity of pancreatitis, necessity of an intensive care unit (ICU) stay, organ failure, readmission, and death. Information on demographics, medical history, biochemical data, severity of the pancreatitis episode (Revised Atlanta Classification), and imaging were obtained for analysis. Logistic regression was used for analysis. Results: A total of 1340 unique patients were included in the analysis. 313 (23.4%) of the patients had pre-existing DM while 1027 (76.6%) did not. The overall cohort was 46.8% female and 81.3% Hispanic. The mean age in the patients with pre-existing DM was 53 ( ± 14) years old, while the non-diabetic cohort was 43 (± 15) years old. Patients with diabetes mellitus were significantly more likely to have moderate-to-severe pancreatitis [OR 1.52 (1.11-2.09)]. With regards to hospital outcomes, the diabetes cohort were more likely to have an intensive care unit (ICU) stay [2.26 (1.65-3.11)], and necessity of ICU interventions such as vasopressors [5.06 (2.25-11.38)], intubation [2.21 (1.13-4.35)], and renal replacement therapy (RRT) [4.77 (1.92-11.88)]. No significant difference was seen in readmission within 30 days [0.79 (0.51-1.23)] but patients with diabetes were more likely to have hospitalization result in death [3.49 (1.41-8.60)]. Conclusion: Within our acute pancreatitis population, patients with diabetes mellitus were more likely to have both local and systemic complications as well as necessity of more invasive hospital interventions such as intubation and vasopressors compared to their non-diabetic counterparts. These results emphasize the importance of adequately controlling patients’ underlying diabetes to minimize risk of hospital complications (Table). Table 1. - Comparison of hospitalization outcomes for acute pancreatitis in diabetics vs. non-diabetics No Diabetesn=1027, (76.6%) Diabetesn=313, (23.4%) P value OR (95% CI) Pancreatitis Severity Mild 857 (83.4%) 238 (76.0%) 0.003 Mod/Severe 170 (16.6%) 75 (24.0%) 0.003 1.52 (1.11-2.09) Organ Failure (any) 104 (10.1%) 54 (17.3%) 0.001 1.69 (1.16-2.44) Respiratory Failure 81 (7.9%) 34 (10.9%) 0.100 Circulatory Failure 20 (2.0%) 15 (4.8%) 0.006 Renal Failure 37 (3.6%) 33 (10.5%) < 0.0001 ICU Stay (yes/no) 138 (13.4%) 82 (26.2%) < 0.0001 2.26 (1.65-3.11) ICU LOHS (days) 0.8 1.5 0.031 Intubation 23 (2.2%) 16 (5.1%) 0.008 2.21 (1.13-4.35) Vasopressors 11 (1.1%) 17 (5.4%) < 0.0001 5.06 (2.25-11.38) RRT 9 (0.9%) 12 (3.8%) < 0.0001 4.77 (1.92-11.88) Readmission within 30 days 116 (11.3%) 29 (9.3%) 0.312 0.79 (0.51-1.23) Death 10 (1.0%) 12 (3.8%) < 0.0001 3.49 (1.41-8.60) Footnote: -OR=odds ratio, from multivariate analysis controlling for age, gender, and comorbidities such as heart failure, chronic kidney disease, and cirrhosis. ICU= intensive care unit; RRT = renal replacement therapy.

A female patient aged 47 years presented with a hemoglobin A1c (HbA1c) level of 54.6%, as measured by ion-exchange high-performance liquid chromatography (HPLC), and a glucose level of 106 mg/dL. The HbA1c was re-evaluated using a turbidimetric inhibition immunoassay and found below the level of detection. Hemoglobinopathy testing led to the identification of a hemoglobin variant consistent with Hb Raleigh, in which a valine → alanine substitution on the beta chain effects a charge difference, resulting in coelution with HbA1c on HPLC and a spuriously high reading. Many Hb variants may interfere with HbA1c measurement and generate misleading results. The unique properties of Hb Raleigh may give rise to analytical errors when evaluating HbA1c using 2 different methods-molecular charge-based (eg, HPLC) and molecular structure-based (eg, immunoassay)-yielding diametrically opposed results. Consequently, recognition and diagnosis of this entity are essential in patients with Hb Raleigh, especially when monitoring long-term glucose control.