Methods to reduce lipemic interference in clinical chemistry tests: a systematic review and recommendations.

OBJECTIVES: Lipemia is the presence of abnormally high lipoprotein concentrations in serum or plasma samples that can interfere with laboratory testing. There is little guidance available from manufacturers or professional bodies on processing lipemic samples to produce clinically acceptable results. This systematic review summarizes existing literature on the effectiveness of lipid removal techniques in reducing interference in clinical chemistry tests. METHODS: A PubMed search using terms relating to lipid removal from human samples for clinical chemistry tests produced 1,558 studies published between January 2010 and July 2021. 15 articles met the criteria for further analyses. RESULTS: A total of 66 analytes were investigated amongst the 15 studies, which showed highly heterogenous study designs. High-speed centrifugation was consistently effective for 13 analytes: albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, creatine kinase (CK), creatinine (Jaffe method), gamma-glutamyl transferase (GGT), glucose (hexokinase-based method), lactate dehydrogenase (LDH), phosphate, potassium, and urea. Lipid-clearing agents were uniformly effective for seven analytes: ALT, AST, total bilirubin, CK, creatinine (Jaffe method), lipase, and urea. Mixed results were reported for the remaining analytes. CONCLUSIONS: For some analytes, high-speed centrifugation and/or lipid-clearing agents can be used in place of ultracentrifugation. Harmonized protocols and acceptability criteria are required to allow pooled data analysis and interpretation of different lipemic interference studies.

A curious case of a negative control line on a dengue duo assay due to interference - A case report.

An elderly patient who presented with 1 week of fever and respiratory symptoms was tested for dengue infection with an Abbott Bioline™ Dengue Duo immunochromatographic assay. Unexpectedly, the control line of the dengue non-structural protein 1 (NS1) component was absent, necessitating result invalidation. It remained absent when the test was repeated on the SD Biosensor Standard™ Q Dengue Duo, but present on the Wells Bio careUSTM Dengue Combo and Asan Easy Test® Dengue DUO assays, suggesting potential interference. Dilution, polyethylene glycol (PEG) precipitation and centrifugation with a 100 kDa filter were performed to reduce/remove the potential interferent. Sera from other patients that showed a control line, and a test line that was either positive or negative for NS1, were used as controls. Upon dilution with negative control serum, a faint control line emerged. PEG precipitation resulted in disappearance of control and test lines in the positive control. Filtration led to emergence of the control line for the patient's serum but caused the test line for the positive control serum to disappear. Overall, investigations suggested the presence of a high molecular weight (>100 kDa) substance which interferes with chicken IgY-anti-chicken IgY binding at the control line of affected assays. Our results highlight two important points: firstly, some commonly used laboratory procedures (e.g. PEG or filtration) may inadvertently remove the target biomarker (e.g. multimeric NS1) and should be interpreted with appropriate controls. Secondly, alternative kits that use a different antigen-antibody combination for the control line can be considered when similar patients are encountered in future.

A systematic review and meta-analysis of individual patient data on the impact of the BIM deletion polymorphism on treatment outcomes in epidermal growth factor receptor mutant lung cancer.

BACKGROUND: A germline deletion in the BIM (BCL2L11) gene has been shown to impair the apoptotic response to tyrosine kinase inhibitors (TKIs) in vitro but its association with poor outcomes in TKI-treated non-small cell lung cancer (NSCLC) patients remains unclear. We conducted a systematic review and meta-analysis on both aggregate and individual patient data to address this issue. RESULTS: In an aggregate data meta-analysis (n = 1429), the BIM deletion was associated with inferior PFS (HR = 1.51, 95%CI = 1.06-2.13, P = 0.02). Using individual patient data (n = 1200), we found a significant interaction between the deletion and ethnicity. Amongst non-Koreans, the deletion was an independent predictor of shorter PFS (Chinese: HR = 1.607, 95%CI = 1.251-2.065, P = 0.0002; Japanese: HR = 2.636, 95%CI = 1.603-4.335, P = 0.0001), and OS (HR = 1.457, 95% CI = 1.063-1.997, P = 0.019). In Kaplan-Meier analyses, the BIM deletion was associated with shorter survival in non-Koreans (PFS: 8.0 months v 11.1 months, P < 0.0005; OS: 25.7 v 30.0 months, P = 0.042). In Koreans, the BIM deletion was not predictive of PFS or OS. MATERIALS AND METHODS: 10 published and 3 unpublished studies that reported survival outcomes in NSCLC patients stratified according to BIM deletion were identified from PubMed and Embase. Summary risk estimates were calculated from aggregate patient data using a random-effects model. For individual patient data, Kaplan-Meier analyses were supported by multivariate Cox regression to estimate hazard ratios (HRs) for PFS and OS. CONCLUSIONS: In selected populations, the BIM deletion is a significant predictor of shorter PFS and OS on EGFR-TKIs. Further studies to determine its effect on response to other BIM-dependent therapeutic agents are needed, so that alternative treatment strategies may be devised.