{"title":"The Hidden Threat in Immunoassays: A Case of Persistent False-Positive CK-MB.","authors":"Siwei Xue, Weiqiang Huang, Degui Ou, Wenda Huang, Jianwen Liu, Zetian Zhong","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>This report aims to explore the significant impact of heterophilic antibodies on CK-MB immunoassays, leading to persistent false-positive results.</p><p><strong>Case report: </strong>A 59-year-old male with a history of coronary artery disease exhibited persistently elevated CK-MB levels for over two years, despite normal troponin I levels. Further investigations, including serial dilution, blocking experiments, and testing across different platforms, confirmed the presence of heterophilic antibody interference, which was responsible for the falsely elevated CK-MB levels.</p><p><strong>Conclusion: </strong>This case underscores the critical importance of recognizing heterophilic antibody interference in immunoassays. The use of appropriate diagnostic approaches, such as blocking antibodies, cross-platform testing, and the integration of additional diagnostic markers, is essential to prevent misdiagnosis and ensure accurate clinical decision-making.</p>","PeriodicalId":8228,"journal":{"name":"Annals of clinical and laboratory science","volume":"55 2","pages":"272-276"},"PeriodicalIF":1.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mansur A Ramalan, Zainab U Ibrahim, Aishatu M Nalado, Hassan A Murtala, Ibrahim D Gezawa, Baba M Musa, Andrew E Uloko, Musa Babashani, Mahmoud U Sani, Zubairu Iliyasu, C William Wester, Hamisu M Salihu, Muktar H Aliyu
{"title":"Adrenal Insufficiency among People Living with HIV in Africa: Does Salivary Cortisol Make a Difference?","authors":"Mansur A Ramalan, Zainab U Ibrahim, Aishatu M Nalado, Hassan A Murtala, Ibrahim D Gezawa, Baba M Musa, Andrew E Uloko, Musa Babashani, Mahmoud U Sani, Zubairu Iliyasu, C William Wester, Hamisu M Salihu, Muktar H Aliyu","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>Diagnosing adrenal insufficiency in people living with HIV (PLWH) is challenging, especially in resource limited settings. Salivary cortisol assessment, however, is simple, minimally invasive, efficient, and cost-effective, making it a viable alternative. We evaluated whether early morning salivary cortisol measurement among PLWH could replace Synacthen test in Africans.</p><p><strong>Methods: </strong>This cross-sectional study included 201 PLWH recruited from the HIV clinic of a tertiary health facility and a comparison group of 200 HIV-negative individuals. We used a locally established cut off and a low-dose Synacthen test to determine adrenal function. Serum and salivary cortisol samples were obtained simultaneously at baseline and during the test (at 30 and 60 minutes).</p><p><strong>Results: </strong>The prevalence of adrenal insufficiency among PLWH was 54.7% when using a salivary cortisol-based locally established cut off, compared to 10.5% using a serum derived diagnostic cut-off (<i>p</i><0.001). Adrenal insufficiency was associated with HIV diagnosis and dolutegravir (DTG) use. Compared to HIV-negative participants, PLWH on DTG had 18 times the odds of developing adrenal insufficiency (adjusted odds ratio [aOR]=18.3, 95% confidence interval [CI]: 9.58-36.5), while PLWH not on DTG had 13 times the odds (aOR=13.7, 95% CI: 6.60-30.3).</p><p><strong>Conclusion: </strong>HIV status is associated with development of adrenal insufficiency. Salivary cortisol measurement could serve as a useful non-invasive tool for diagnosing adrenal insufficiency among PLWH in similar settings.</p>","PeriodicalId":8228,"journal":{"name":"Annals of clinical and laboratory science","volume":"55 2","pages":"212-219"},"PeriodicalIF":1.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Exploring Ovarian Cancer Prediction Models and Potential Markers Using Machine Learning.","authors":"Huijing Luo, Xiaofang Zhang, Dongsha Shi, Yanv Ren, Wenyan Tian, Ruiyu Ma, Zuoliang Dong","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>To develop machine learning models, facilitate a more accurate diagnosis of ovarian cancer (OC), and explore potential markers.</p><p><strong>Methods: </strong>Overall, 311 patients diagnosed with OC, 56 with borderline ovarian tumors (OTs), and 368 patients with benign OTs were defined as derivation cohort and randomly divided into training (70%) and internal validation (30%) sets. An independent external validation cohort was also established. A total of 34 variables including patients' demographic characteristics and laboratory test results were collected. Models were developed using artificial neural network, support vector machine, random forest, and extreme gradient boosting (XGBoost).</p><p><strong>Results: </strong>All four models achieved high accuracy, with XGBoost achieving the highest area under the curve (AUC). When using the XGBoost model to differentiate OC from borderline and benign OTs, the AUC and 95% confidence interval, sensitivity, specificity, positive predictive value, and negative predictive value of the training set were 0.973 (0.962-0.985), 84.2%, 96.6%, 93.9%, and 90.6%, respectively. For the internal validation set, the values were 0.932 (0.897-0.966), 74.7%, 92.0%, 85.5%, and 85.2%. The eight most important variables were human epididymis protein 4, carbohydrate antigen 125, lactate dehydrogenase, D-dimer, age, testosterone, follicle-stimulating hormone, and hemoglobin. Subgroup analyses also revealed that this model exhibited outstanding performance in identifying early-stage OC and epithelial OC.</p><p><strong>Conclusion: </strong>Machine learning models demonstrate excellent accuracy in distinguishing OC from borderline and benign OTs, with several potential markers being validated.</p>","PeriodicalId":8228,"journal":{"name":"Annals of clinical and laboratory science","volume":"55 2","pages":"153-165"},"PeriodicalIF":1.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jianbo Yang, Kimberly Robyak, Christopher Hamilton, Yusheng Zhu
{"title":"Development and Validation of a Serum Total Testosterone LC-MS/MS assay Certified by the CDC Hormone Standardization Program.","authors":"Jianbo Yang, Kimberly Robyak, Christopher Hamilton, Yusheng Zhu","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>We aimed to develop and validate a serum testosterone liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay and sought certification by the CDC Hormone Standardization (HoSt) Program.</p><p><strong>Methods: </strong>Serum samples mixed with internal standards were extracted with hexane: ethyl acetate. An Agilent Poroshell 120 EC-C18 column and an Agilent 1260 Infinity HPLC system were used for liquid chromatography. An Agilent 6460C QQQ triple quadrupole mass spectrometer was used for multiple reaction monitoring. The assay was validated for matrix effect, lower limit of quantification, analytical measurement range, precision, accuracy, dilution, specificity, interference, and carryover.</p><p><strong>Results: </strong>The LC-MS/MS testosterone assay demonstrated an analytical measurement range (AMR) of 2.9-2330.4 ng/dl with a mean bias of 0.4% (95% CI: -2.8% to 3.6%) for the certified reference materials from the HoSt Program. The total CVs were 2.4-4.7%. The correlation between this LC-MS/MS (y) and a reference laboratory LC-MS/MS (x) was excellent: y=0.939x-8.3 (R=0.9978). The method was certified by the CDC HoSt Program.</p><p><strong>Conclusion: </strong>An accurate and sensitive LC-MS/MS assay to measure serum testosterone is developed, validated, and certified by the HoSt Program. The assay can be used for serum testosterone testing in pediatric, female, and hypogonadal male populations.</p>","PeriodicalId":8228,"journal":{"name":"Annals of clinical and laboratory science","volume":"55 2","pages":"192-202"},"PeriodicalIF":1.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sultan Alasmari, Faisal Alhajori, Mohammed Makkawi
{"title":"Diagnostic and Prognostic Value of Hematological and Biochemical Profiles in Pediatric Hematologic Malignancies.","authors":"Sultan Alasmari, Faisal Alhajori, Mohammed Makkawi","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to evaluate the hematological parameters and biochemical profiles of common pediatric hematological malignancies in the Madinah region of Saudi Arabia. The objective was to identify a factor that could be utilized for screening and/or prognosis.</p><p><strong>Methods: </strong>This study is a retrospective analysis conducted from 2016 to 2022. The research involved 172 children under the age of 16 who had received a diagnosis of hematological malignancies. The data was obtained from King Salman Medical City's Maternity and Children's Hospital located in Madinah, Saudi Arabia.</p><p><strong>Results: </strong>This study found 13 types of HMs. The hematological and biochemical profiles have been assessed for the four predominant HM subtypes in the research region: B-cell acute lymphoblastic leukemia (B-ALL), acute myelomonocytic leukemia (AML-M4), T-cell acute lymphoblastic leukemia (T-ALL), and acute myeloid leukemia M3 (AML-M3). Only AML-M4 and T-ALL had significantly variable WBCs, whereas all four types evaluated in this study had significantly different Hb and platelets. WBC differentials were varied, but some were significant, and others were not. Biochemical profile data on the four prevalent types varied. B-ALL had elevated AST, GGT, and BUN. However, only GGT and BUN were significant in AML-M4. T-ALL had significant ALT, AST, GGT, and CREA. AST alone was significant in AML-M3. LDH was noticeably significant in all four categories.</p><p><strong>Conclusion: </strong>In this study, 13 HMs were identified. The study assessed the hematological and biochemical profiles of the four most common HM subtypes in the region. Pediatric malignancies, although infrequent, play a significant role in child mortality. The data from this study may facilitate swift disease diagnosis and prognosis.</p>","PeriodicalId":8228,"journal":{"name":"Annals of clinical and laboratory science","volume":"55 2","pages":"203-211"},"PeriodicalIF":1.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tamar A Smith-Norowitz, Yecheskel Gold, Esther M Norowitz, Rauno Joks, Stephan Kohlhoff
{"title":"Effect of Serum IgE on Clinical Variables and Comorbidities Associated with Asthma Severity in Adults with Asthma in Brooklyn, New York.","authors":"Tamar A Smith-Norowitz, Yecheskel Gold, Esther M Norowitz, Rauno Joks, Stephan Kohlhoff","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>Elevated serum immunoglobulin (Ig)E levels are associated with increased asthma and atopy severity in adults. The aim of this study was to determine whether levels of serum IgE or allergic sensitization affected clinical variables and increased the risk of asthma severity in adults with asthma in Brooklyn, NY.</p><p><strong>Methods: </strong>Retrospective study of adults with moderate asthma and atopy (N=66, mean age 49+/-14 y/o, 75% female). The primary analysis assessed the relationship between total serum IgE, presence of specific IgE (skin prick test), and clinical variables (body mass index (BMI) and pulmonary function tests). Data preparation and analysis was conducted using SPSS (Version 28.0.1.1).</p><p><strong>Results: </strong>Subjects with elevated total serum IgE had higher levels of pulmonary obstruction/asthma severity (FEV1/FVC, mean difference: -5.62±3.4, P=0.05 and FEF25-75, mean difference: 15.49±9.5, P= 0.05) (T-test for equality of means). Mean BMI was higher in subjects with allergic sensitization versus those without (32.59±8.14 vs. 29.5±4.4, <i>P</i>=0.05).</p><p><strong>Conclusion: </strong>In adults with asthma there was a trend observed toward an association of atopy with clinical variables, including decreased lung function and higher BMI. The presence of high serum IgE levels should be considered when assessing asthma outcomes.</p>","PeriodicalId":8228,"journal":{"name":"Annals of clinical and laboratory science","volume":"55 2","pages":"220-223"},"PeriodicalIF":1.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Early Prediction of Acute Gastrointestinal Injury in Patients with Acute Pancreatitis by C-reactive Protein/Albumin Ratio Combined with IL-23.","authors":"KeWu Chen, Dong Yang, ChangYun Luo","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>To explore the effect of C-reactive protein/albumin ratio (CAR) combined with IL-23 on early prediction of acute gastrointestinal injury (AGI) in patients with acute pancreatitis (AP).</p><p><strong>Methods: </strong>The clinical data of 120 AP patients were retrospectively analyzed, of which 103 patients were in the non-severe AP group and 20 were in the severe AP group (SAP group). The medical records and clinical indicators of all the patients were collected and statistically analyzed.</p><p><strong>Results: </strong>At admission, there was no statistically significant difference in temperature, respiratory rate, alanine aminotransferase, aspartate aminotransferase, LPS, and total bilirubin, and there was a statistically significant difference in heart rate, IL-23, procalcitonin, blood creatinine, CRP, blood urea nitrogen, serum albumin, blood glucose, and CAR. Multifactorial logistic regression analysis revealed that CAR and IL-23 were significant predictors of SAP. CAR and IL-23 at admission were positively correlated with BISAP score (r=0.301, <i>P</i><0.001; r=0.295, <i>P</i><0.01). ROC curves showed that the area under the curve of CAR was 0.732 (95% CI: 0.770-0.901), with a sensitivity of 75.00% and a specificity of 85.9%, respectively, and the area under the curve of IL-23 was 0.848 (95% CI: 0.731-0.887), with a sensitivity of 80% and a specificity of 71.4%, respectively. The area under the curve of CAR and IL-23 was 0.899 (95% CI: 0.846-0.936), with a sensitivity of 78% and a specificity of 86.2%.</p><p><strong>Conclusion: </strong>CAR and IL-23 have significant advantages in predicting the severity of AGI in patients with AP, and their predictive efficacy is further increased especially when they are combined.</p>","PeriodicalId":8228,"journal":{"name":"Annals of clinical and laboratory science","volume":"55 2","pages":"224-230"},"PeriodicalIF":1.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"In Memoriam: Kilmer S. McCully, MD, PhD (1933-2025).","authors":"Charles D Hawker, Roger L Bertholf","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":8228,"journal":{"name":"Annals of clinical and laboratory science","volume":"55 2","pages":"151-152"},"PeriodicalIF":1.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gang Wang, Xue Zhao, Guangyu He, Zhuo Li, Guixia Wang, You Lv
{"title":"Effect of Butyric Acid on Apoptosis of Pancreatic β Cells.","authors":"Gang Wang, Xue Zhao, Guangyu He, Zhuo Li, Guixia Wang, You Lv","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>Islet β-cell dysfunction and insulin resistance are associated with obesity-associated type 2 diabetes mellitus. Short-chain fatty acids (SCFAs) are important regulatory factors for energy metabolism. We aimed to determine the effects of butyric acid (BA) on β-cell apoptosis in type 2 diabetes.</p><p><strong>Methods: </strong>A db/db transgenic mouse model and lipopolysaccharide (LPS)-stimulated β-cell model were used to determine the effects of BA on β-cells. The viability and apoptosis of β cells were determined using the MTT assay and flow cytometry, respectively. The expression of inflammatory factors IL-1β, TNF-<i>α</i>, IL-6, and IL-10 was measured using quantitative PCR. Activation of the NF-<i>κ</i>B signaling pathway was detected by quantitative PCR and Western blotting. Fasting plasma glucose (FPG), fasting insulin (FINS), total cholesterol (TC), and triglyceride (TG) levels were assessed to evaluate glycolipid metabolism. Intestinal flora and SCFA analyses were performed to explore the changes in the gut microbiota.</p><p><strong>Results: </strong>Butyric acid treatment notably suppressed LPS-induced expression of pro-inflammatory cytokines and improved β-cell apoptosis. The levels of TC, TG, FPG, and FINS were significantly elevated in diabetic mice and decreased after BA treatment. The expression of the β-cell regulatory genes Maf-A and Foxo1 was notably decreased in diabetes, and BA treatment restored their expression levels.</p><p><strong>Conclusions: </strong>Butyric acid notably alleviated β-cell apoptosis and the secretion of inflammatory cytokines in diabetes by suppressing NF-<i>κ</i>B signaling. Butyric acid improves the intestinal flora of diabetic mice, suggesting its potential as a novel therapeutic agent for diabetes.</p>","PeriodicalId":8228,"journal":{"name":"Annals of clinical and laboratory science","volume":"55 2","pages":"259-267"},"PeriodicalIF":1.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"<i>Technical Note:</i> Experience of Implementing Tacrolimus Immunoassay on the Alinity i Analyzer in an Academic Medical Center: Small Percentage of Specimens Were Sent to Reference Laboratory for LC-MS/MS Analysis.","authors":"Melody Nelson, Tracy Kisler, Kelsey Woodard, Amitava Dasgupta","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>Liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) is considered the gold standard for analysis of tacrolimus as this method is free from metabolite interferences. Due to complexity of analysis and initial high cost, many hospital laboratories use immunoassays for routine monitoring of tacrolimus. In 2023, we implemented a Federal Food and Drug Administration (FDA) approved Chemiluminescent microparticle immunoassay (CMIA) of tacrolimus on the Alinity i analyzer with an option for physicians to request LC-MS/MS analysis if they were not satisfied with the immunoassay result.</p><p><strong>Methods: </strong>CMIA tacrolimus was performed on the Alinity i analyzer, and the result was reported within four hours. After evaluating a particular tacrolimus result, if a physician requested LC-MS/MS analysis, the same whole blood specimen was sent to the reference laboratory. Then, we compared LC-MS/MS value with initial immunoassay result.</p><p><strong>Results: </strong>In a 12-month period, 25,897 tacrolimus tests were ordered by physicians. Only 388 specimens (1.49%) were sent to the reference laboratory for LC-MS/MS analysis. The overall correlation between LC-MS/MS value (x-axis) and immunoassay result was excellent (y=1.045x+0.652, r=0.96, n=388). Out of 388 specimens, only 70 specimens were considered discordant due to more than 20% bias between the LC-MS/MS and immunoassay values. When these specimens were compared, the regression equation was 1.277x+0.412, r=0.95.</p><p><strong>Conclusions: </strong>The CMIA assay on the Alinity i analyzer is suitable for routine therapeutic drug monitoring of tacrolimus with high physician satisfaction.</p>","PeriodicalId":8228,"journal":{"name":"Annals of clinical and laboratory science","volume":"55 2","pages":"268-271"},"PeriodicalIF":1.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}