Accounting for differences between serum and plasma: An indirect approach to derive reference intervals for total protein, albumin, and globulin.

BACKGROUND: Observable quantitative variations exist between plasma and serum in routine protein measurements, often not reflected in standard reference intervals. In this study, we describe an indirect approach for estimating a combined reference interval (RI) (i.e., serum and plasma), for commonly ordered protein measurands: total protein, albumin, and globulin. METHODS: We applied an indirect reference interval estimation for protein measurements in serum and plasma using data from July 2018 to February 2024. The data were divided into three Epochs based on a period of plasma separator tube shortage during the COVID-19 pandemic. Bootstrap resampling was used to calculate RIs and corresponding 95% confidence intervals for each month. RESULTS: Our results demonstrate notable changes in RI limits for total protein, albumin, and globulin between Epochs, reflecting the influence of changing sample matrix. A combined RI was identified for all components and verified using plasma and serum samples from 20 healthy individuals and retrospective analysis of flagging rates on our outpatient population using new and historical RIs. CONCLUSION: The study demonstrates notable differences in the RIs for total protein, albumin, and globulin when container type changes. In addition, the results demonstrate the effectiveness of big data analytics in deriving RIs and highlights the necessity of continuous RI assessment and adjustment based on the patient population and acceptable specimen types.

Puzzling undetectable haptoglobin in a transfused pregnant patient.

BACKGROUND-AIM: Pregnancy induces physiological changes that can affect serologic and immunologic markers, potentially resulting in lower or undetectable haptoglobin values compared to non-pregnant counterparts. Such variations may lead to inaccurate diagnosis of hemolysis. METHODS: We report a case of a patient in second trimester of pregnancy receiving induction chemotherapy due to B-cell acute lymphocytic leukemia with undetectable haptoglobin levels in a routine laboratory sample collected less than 12 h posttransfusion of red cell unit. Despite undetectable haptoglobin, lactate dehydrogenase (LD) was within reference intervals (RI). The patient was evaluated for acute hemolytic transfusion reaction (AHTR) and followed up. Haptoglobin levels showed an upward trend during follow-up visits, reaching 15 mg/dL, and within RI in the third trimester. RESULTS: The patient did not meet the Center for Disease Control (CDC) criteria for AHTR. Alternative explanations for the observed laboratory findings were explored. Undetectable haptoglobin levels were attributed to various factors, including recent RBC transfusion, pregnancy-related physiological changes, and potential hyperhydration treatment plan due to chemotherapy. CONCLUSION: This case underscores the importance of cautious interpretation of laboratory results in pregnant patients, necessitating trimester-specific reference intervals for haptoglobin. A multidisciplinary approach to patient care is crucial for accurate diagnosis and management.

Biomarkers vs Machines: The Race to Predict Acute Kidney Injury.

BACKGROUND: Acute kidney injury (AKI) is a serious complication affecting up to 15% of hospitalized patients. Early diagnosis is critical to prevent irreversible kidney damage that could otherwise lead to significant morbidity and mortality. However, AKI is a clinically silent syndrome, and current detection primarily relies on measuring a rise in serum creatinine, an imperfect marker that can be slow to react to developing AKI. Over the past decade, new innovations have emerged in the form of biomarkers and artificial intelligence tools to aid in the early diagnosis and prediction of imminent AKI. CONTENT: This review summarizes and critically evaluates the latest developments in AKI detection and prediction by emerging biomarkers and artificial intelligence. Main guidelines and studies discussed herein include those evaluating clinical utilitiy of alternate filtration markers such as cystatin C and structural injury markers such as neutrophil gelatinase-associated lipocalin and tissue inhibitor of metalloprotease 2 with insulin-like growth factor binding protein 7 and machine learning algorithms for the detection and prediction of AKI in adult and pediatric populations. Recommendations for clinical practices considering the adoption of these new tools are also provided. SUMMARY: The race to detect AKI is heating up. Regulatory approval of select biomarkers for clinical use and the emergence of machine learning algorithms that can predict imminent AKI with high accuracy are all promising developments. But the race is far from being won. Future research focusing on clinical outcome studies that demonstrate the utility and validity of implementing these new tools into clinical practice is needed.

Nitrous oxide abuse direct measurement for diagnosis and follow-up: update on kinetics and impact on metabolic pathways.

Recreational use of nitrous oxide (N2O) has become a major health issue worldwide, with a high number of clinical events, especially in neurology and cardiology. It is essential to be able to detect and monitor N2O abuse to provide effective care and follow-up to these patients. Current recommendations for detecting N2O in cases of recreational misuse and consumption markers are lacking. We aimed to update current knowledge through a review of the literature on N2O measurement and kinetics. We reviewed the outcomes of experiments, whether in preclinical models (in vitro or in vivo), or in humans, with the aim to identify biomarkers of intoxication as well as biomarkers of clinical severity, for laboratory use. Because N2O is eliminated 5 min after inhalation, measuring it in exhaled air is of no value. Many studies have found that urine and blood matrices concentrations are connected to ambient concentrations, but there is no similar data for direct exposure. There have been no studies on N2O measurement in direct consumers. Currently, patients actively abusing N2O are monitored using effect biomarkers (biomarkers related to the effects of N2O on metabolism), such as vitamin B12, homocysteine and methylmalonic acid.

Cannabis positivity rates in 17 emergency departments across the United States with varying degrees of marijuana legalization.

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.

A preliminary study of hydrocodone and hydromorphone to oxycodone ratios for distinguishing impurities from independent opioid use.

BACKGROUND: Urine drug testing (UDT) monitors prescription compliance and/or drug abuse. However, interpretation of UDT results obtained by liquid chromatography-tandem mass spectrometry (LC-MS-MS) can be complicated by the presence of drug impurities that are detected by highly sensitive methods. Hydrocodone is a drug impurity that can be found as high as 1% in oxycodone pills. OBJECTIVES: We evaluated the frequency and concentration of hydrocodone and its metabolite, hydromorphone, in patients taking oxycodone to check if the ratio of hydrocodone or hydromorphone to oxycodone could distinguish between oxycodone only use from those consuming additional opiates. DESIGN & METHODS: We correlated LC-MS/MS results with medication records of 319 patients with positive oxycodone results over 7 months (4/2021-11/2021). RESULTS: Fifteen of 319 patients with positive oxycodone results were taking oxycodone only. For these 15 patients, the mean ratio of hydrocodone to oxycodone was 0.57% (range 0.05%-3.35%), and the mean ratio of hydromorphone to oxycodone was 0.81% (range 0.18-3.51%). CONCLUSIONS: Hydrocodone and/or hydromorphone are detectable in patients taking only oxycodone and can likely be identified as an impurity if their calculated ratio to oxycodone is <1 %. Further validation of the ratios in a larger sample size is recommended.

Resolving icteric interference by a novel photoisomerization device: Bilibox.

Icterus, a phenomenon caused by bilirubin elevation in the blood, is a common endogenous interference in chemistry testing, occurring either spectrally or through chemical reactivity with assay reagents. Often, laboratories have few options other than to dilute or reject samples exceeding icteric thresholds. However, recent studies have optimized in vitro photoisomerization of bilirubin to a 17-minute bilirubin half-life using 500 nm light at 37 °C. Using an enzymatic creatinine assay as a model, due to its prevalence in routine laboratory testing and susceptibility to icteric interference, our study explores the usage of in vitro photoisomerization by replicating these conditions in a device, the Bilibox, as means of resolving icterus in laboratory testing. Left-over icteric and non-icteric clinical samples, collected by lithium heparin vacutainer (n = 10), were analyzed for baseline creatinine, diluted creatinine (1:4 0.9 % NaCl), total bilirubin, direct bilirubin, and hemolysis, icterus and lipemia (HIL) indices. Samples were then placed in the Bilibox in two intervals of 30 min with repeat measurements of the aforementioned analytes. On average, icteric-index, total bilirubin (TBIL), and direct bilirubin (DBIL) decreased by 33.5, 39.1 and 39.9 % respectively following 30 min of Bilibox treatment; and by 47.6 %, 63.7 % and 59.8 % following 60 min. The average percent difference between the pre-exposure diluted and undiluted creatinine was 5.8 %, demonstrating the icterus interference. Following Bilibox treatment, the difference between undiluted (post-exposure) and diluted (pre-exposure) creatinine decreased to 0.02 % (p = 0.0232) and 2.2 % (p = 0.0021) at 30 and 60 min of treatment respectively, demonstrating resolution of interference. Consequently, photoisomerization can be utilized as an additional and reasonably quick method for resolving icterus when dilutional methods cannot be applied.

Contamination of clinical blood samples with crystalloid solutions: An experimental approach to derive multianalyte delta checks.

BACKGROUND: Laboratorians are left unguided by a paucity of literature on how to configure rules for the detection of intravenous (IV) fluid contamination in blood samples. We designed a study to determine the in vitro effect of increasing blood sample contamination from commonly used crystalloid solutions and how these observations can guide the derivation of multianalyte delta checks to detect such pre-analytical error. METHODS: In this study, we spiked increasing volumes of commonly used IV fluids (normal saline (NS), lactated ringers (LR), and 5% dextrose) into blood samples that were collected from healthy donors. Routine chemistry analytes were measured and compared between neat and contrived samples. From these observations, we derived several permutations of multianalyte delta checks using the basic metabolic panel framework and evaluated rule performance using retrospective data. RESULTS: The wet chemistry experiments showed that increasing the volume of crystalloid solution contamination significantly changed several analytes. Subsequently derived multianalyte delta check procedures were applied to retrospective data. For all IV fluids tested, smaller magnitudes of analyte change resulted in more samples flagged. CONCLUSION: Multianalyte delta checks may be an effective method for the detection of IV fluid contamination.

Rapid serum tubes reduce transport hemolysis and false positive rates for high-sensitivity troponin T.

INTRODUCTION: Hemolysis in the emergency department (ED) can significantly delay results and appropriate action. We evaluated the main sources of hemolysis during sample collection, and to evaluate the use of rapid serum tubes (RST) as a transport hemolysis-mitigating measure for high-sensitivity troponin T (hs-cTnT) testing. METHODS: We examined the effect of tube type, tube fill, types of sample draw and collection methods on hemolysis and hs-cTnT in samples (n = 158) from ED patients. We also compared hs-cTnT values in paired RST and plasma separate tube (PST) samples that were hemolysis-free. RESULTS: The primary source of hemolysis in samples collected in the ED was underfilling tubes. In both tube types, PST and RST, filled tubes showed a median reduction in hemolysis of 69.1 % (p < 0.0001). Blood collected in RST also experienced less hemolysis compared to PST. In hemolysis-free samples, false positive results in PST were noted in patients with hs-cTnT values < 50 ng/l. CONCLUSION: We suggest that proper tube filling during sample collection and use of RST tubes can significantly reduce the effects of hemolysis. In addition, laboratories should be aware that PST tubes have a non-trivial rate of false positives when hs-cTnT < 50 ng/l.