Pub Date : 2025-12-02DOI: 10.1093/clinchem/hvaf120
Steffen Halbgebauer, Badrieh Fazeli, Veronika Klose, Gabriele Nagel, Angela Rosenbohm, Dietrich Rothenbacher, Franziska Bachhuber, Sarah Jesse, Markus Otto, G Bernhard Landwehrmeyer, Ahmed Abdelhak, Axel Petzold, Albert C Ludolph, Hayrettin Tumani
Background: Serum glial fibrillary acidic protein (GFAP) is a biomarker for astrocytic injury and astrogliosis. Concentrations are elevated in numerous neurological disorders, including a pronounced increase in Alzheimer disease (AD). However, GFAP levels in the serum also increase with age. Consequently, the integration of GFAP levels into clinical routine and their interpretation demands age-adjusted reference values.
Methods: Serum from 1273 subjects (952 noninflammatory and nonneurodegenerative neurological controls and 321 subjects with AD) was analyzed for GFAP using the microfluidic Ella system. Age-dependent serum GFAP reference values were estimated by additive quantile regression analysis and visualized with percentiles and z-scores.
Results: AD exhibited elevated serum GFAP levels in comparison to control patients (P < 0.0001). This remained the case when the newly generated age-corrected z-scores were applied (P < 0.0001). In the control cohort, a nonlinear elevation of serum GFAP with increasing age was observed (Spearman correlation coefficient 0.62, 95% CI 0.58-0.66, P < 0.0001). In contrast, the AD cohort exhibited a more linear increase (0.16, 95% CI 0.05-0.26, P = 0.004). Age-dependent cut-offs for serum GFAP were determined for different AD age groups. The calculated areas under the curve (AUCs; 0.97) demonstrated excellent diagnostic test performance in the early-onset age group. This effect was less marked in the elderly subjects (AUC 0.72).
Conclusions: Our novel GFAP z-scores enable the integration and interpretation of serum GFAP levels in clinical practice, moving from the group to individual level. They support both intra- and interindividual interpretation of single GFAP levels in neurological diseases with astrocytic pathology, including an accurate discrimination of AD.
背景:血清胶质原纤维酸性蛋白(GFAP)是星形胶质细胞损伤和星形胶质增生的生物标志物。在许多神经系统疾病中浓度升高,包括阿尔茨海默病(AD)的显著增加。然而,血清中GFAP水平也随着年龄的增长而增加。因此,将GFAP水平纳入临床常规及其解释需要年龄调整的参考值。方法:采用微流控Ella系统分析1273例血清GFAP,其中952例为非炎症性和非神经退行性神经对照,321例为AD患者。年龄依赖性血清GFAP参考值通过加性分位数回归分析估计,并以百分位数和z分数可视化。结果:AD患者血清GFAP水平高于对照组(P < 0.0001)。当应用新生成的年龄校正z分数时,情况仍然如此(P < 0.0001)。在对照组中,血清GFAP随年龄增长呈非线性升高(Spearman相关系数0.62,95% CI 0.58-0.66, P < 0.0001)。相比之下,AD组表现出更线性的增加(0.16,95% CI 0.05-0.26, P = 0.004)。测定不同AD年龄组血清GFAP的年龄依赖性截止值。计算出的曲线下面积(auc; 0.97)在早发年龄组中表现出良好的诊断测试性能。这种效应在老年受试者中不太明显(AUC为0.72)。结论:我们的新GFAP z-评分能够在临床实践中整合和解释血清GFAP水平,从群体水平转移到个体水平。它们支持在星形细胞病理的神经系统疾病中单个GFAP水平的个体内和个体间解释,包括对AD的准确区分。
{"title":"Age-Specific Control and Alzheimer Disease Reference Curves and z-Scores for Glial Fibrillary Acidic Protein in Blood.","authors":"Steffen Halbgebauer, Badrieh Fazeli, Veronika Klose, Gabriele Nagel, Angela Rosenbohm, Dietrich Rothenbacher, Franziska Bachhuber, Sarah Jesse, Markus Otto, G Bernhard Landwehrmeyer, Ahmed Abdelhak, Axel Petzold, Albert C Ludolph, Hayrettin Tumani","doi":"10.1093/clinchem/hvaf120","DOIUrl":"10.1093/clinchem/hvaf120","url":null,"abstract":"<p><strong>Background: </strong>Serum glial fibrillary acidic protein (GFAP) is a biomarker for astrocytic injury and astrogliosis. Concentrations are elevated in numerous neurological disorders, including a pronounced increase in Alzheimer disease (AD). However, GFAP levels in the serum also increase with age. Consequently, the integration of GFAP levels into clinical routine and their interpretation demands age-adjusted reference values.</p><p><strong>Methods: </strong>Serum from 1273 subjects (952 noninflammatory and nonneurodegenerative neurological controls and 321 subjects with AD) was analyzed for GFAP using the microfluidic Ella system. Age-dependent serum GFAP reference values were estimated by additive quantile regression analysis and visualized with percentiles and z-scores.</p><p><strong>Results: </strong>AD exhibited elevated serum GFAP levels in comparison to control patients (P < 0.0001). This remained the case when the newly generated age-corrected z-scores were applied (P < 0.0001). In the control cohort, a nonlinear elevation of serum GFAP with increasing age was observed (Spearman correlation coefficient 0.62, 95% CI 0.58-0.66, P < 0.0001). In contrast, the AD cohort exhibited a more linear increase (0.16, 95% CI 0.05-0.26, P = 0.004). Age-dependent cut-offs for serum GFAP were determined for different AD age groups. The calculated areas under the curve (AUCs; 0.97) demonstrated excellent diagnostic test performance in the early-onset age group. This effect was less marked in the elderly subjects (AUC 0.72).</p><p><strong>Conclusions: </strong>Our novel GFAP z-scores enable the integration and interpretation of serum GFAP levels in clinical practice, moving from the group to individual level. They support both intra- and interindividual interpretation of single GFAP levels in neurological diseases with astrocytic pathology, including an accurate discrimination of AD.</p>","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":"1234-1242"},"PeriodicalIF":6.3,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145279030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-02DOI: 10.1093/clinchem/hvaf117
Louis Nevejan, Xavier Bossuyt
{"title":"Commentary on Aberrant Plasma Cells in the Absence of M-protein: Ancillary Testing beyond Protein Electrophoresis.","authors":"Louis Nevejan, Xavier Bossuyt","doi":"10.1093/clinchem/hvaf117","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf117","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"71 12","pages":"1200"},"PeriodicalIF":6.3,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145654068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-02DOI: 10.1093/clinchem/hvaf130
Maria Alice Willrich, Linda B Baughn
{"title":"Commentary on Aberrant Plasma Cells in the Absence of M-Protein: Ancillary Testing beyond Protein Electrophoresis.","authors":"Maria Alice Willrich, Linda B Baughn","doi":"10.1093/clinchem/hvaf130","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf130","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"71 12","pages":"1201"},"PeriodicalIF":6.3,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145654008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-02DOI: 10.1093/clinchem/hvaf102
Andrew M Ford, Alberto Rubio Tapia
{"title":"The Devil Is in the Details: Clinical Relevance of Serologic Antibody Titers to Predict the Diagnosis of Celiac Disease in Pediatric Type 1 Diabetes.","authors":"Andrew M Ford, Alberto Rubio Tapia","doi":"10.1093/clinchem/hvaf102","DOIUrl":"10.1093/clinchem/hvaf102","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":"1184-1185"},"PeriodicalIF":6.3,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-02DOI: 10.1093/clinchem/hvaf106
Vrajesh Pandya
{"title":"Transdermal GFR Signals a New Horizon in Renal Diagnostics.","authors":"Vrajesh Pandya","doi":"10.1093/clinchem/hvaf106","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf106","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"71 12","pages":"1281-1282"},"PeriodicalIF":6.3,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145653995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-19DOI: 10.1093/clinchem/hvaf132
Khushbu Patel,Mitchell G Scott,Aasne K Aarsand,Ann M Gronowski,Shannon Haymond,Christina Lockwood,Nader Rifai,Mark D Zarella
{"title":"The Changing Face of Academic Laboratory Medicine-A Decade Later and Beyond.","authors":"Khushbu Patel,Mitchell G Scott,Aasne K Aarsand,Ann M Gronowski,Shannon Haymond,Christina Lockwood,Nader Rifai,Mark D Zarella","doi":"10.1093/clinchem/hvaf132","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf132","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"5 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145554742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-13DOI: 10.1093/clinchem/hvaf162
Andrea L Benedet, Burak Arslan, Kubra Tan, Hanna Huber, Ilaria Pola, Guglielmo Di Molfetta, Hlin Kvartsberg, Anna Orduña Dolado, Shorena Janelidze, Kaj Blennow, Henrik Zetterberg, Oskar Hansson, Pedro Rosa-Neto, Nicholas J Ashton
Background Phosphorylated tau 217 (p-tau217) has emerged as a leading blood-based biomarker for Alzheimer disease (AD). While typically measured in plasma, serum is a widely used matrix in clinical laboratories, yet few p-tau217 assays have been validated for serum. Evaluating serum p-tau217 performance is essential for expanding its use in clinical and research settings, particularly for cohorts with only serum samples available. Methods We quantified p-tau217 in plasma and serum from individuals within the AD continuum (n = 100; mean age 72.5 ± 5.0 years; 54% female) using 6 assays across 4 platforms. Spearman correlation, Passing–Bablok regression, and receiver operating characteristics analysis were used to assess intermatrix agreement and diagnostic performance. Specific validation parameters (e.g., precision, parallelism, dilution linearity, stability) were evaluated in both matrices. Results High correlations between plasma and serum were observed for most assays (ρ > 0.8), though plasma often yielded higher concentrations. Notably, the Lumipulse assay showed near-perfect correlation (ρ = 0.98) and minimal bias. Fold changes in p-tau217 levels across the AD continuum were comparable between matrices, though cutoffs for detecting AD pathology differed. Applying plasma-derived cutoffs to serum resulted in misclassification rates ranging from 16% to 47%, except for Lumipulse (10% in serum vs 5% in plasma). Not all assays performed equally in serum, as reflected in validation metrics. Conclusions Serum p-tau217, across multiple platforms, shows strong correlations with plasma p-tau217 and reflected comparable patterns across the AD continuum. However, absolute concentrations differed for most assays, thus requiring differing disease specific cutoffs. Most of the evaluated platforms demonstrated reliable quantification of p-tau217 in serum, yielding satisfactory validation performance. These findings support serum as a viable alternative to plasma for p-tau217 quantification in both research and clinical settings, provided matrix-specific validation is ensured.
{"title":"Diagnostic Value of Serum p-tau217 in Alzheimer Disease: Equal to Plasma in Levels and Clinical Utility?","authors":"Andrea L Benedet, Burak Arslan, Kubra Tan, Hanna Huber, Ilaria Pola, Guglielmo Di Molfetta, Hlin Kvartsberg, Anna Orduña Dolado, Shorena Janelidze, Kaj Blennow, Henrik Zetterberg, Oskar Hansson, Pedro Rosa-Neto, Nicholas J Ashton","doi":"10.1093/clinchem/hvaf162","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf162","url":null,"abstract":"Background Phosphorylated tau 217 (p-tau217) has emerged as a leading blood-based biomarker for Alzheimer disease (AD). While typically measured in plasma, serum is a widely used matrix in clinical laboratories, yet few p-tau217 assays have been validated for serum. Evaluating serum p-tau217 performance is essential for expanding its use in clinical and research settings, particularly for cohorts with only serum samples available. Methods We quantified p-tau217 in plasma and serum from individuals within the AD continuum (n = 100; mean age 72.5 ± 5.0 years; 54% female) using 6 assays across 4 platforms. Spearman correlation, Passing–Bablok regression, and receiver operating characteristics analysis were used to assess intermatrix agreement and diagnostic performance. Specific validation parameters (e.g., precision, parallelism, dilution linearity, stability) were evaluated in both matrices. Results High correlations between plasma and serum were observed for most assays (ρ &gt; 0.8), though plasma often yielded higher concentrations. Notably, the Lumipulse assay showed near-perfect correlation (ρ = 0.98) and minimal bias. Fold changes in p-tau217 levels across the AD continuum were comparable between matrices, though cutoffs for detecting AD pathology differed. Applying plasma-derived cutoffs to serum resulted in misclassification rates ranging from 16% to 47%, except for Lumipulse (10% in serum vs 5% in plasma). Not all assays performed equally in serum, as reflected in validation metrics. Conclusions Serum p-tau217, across multiple platforms, shows strong correlations with plasma p-tau217 and reflected comparable patterns across the AD continuum. However, absolute concentrations differed for most assays, thus requiring differing disease specific cutoffs. Most of the evaluated platforms demonstrated reliable quantification of p-tau217 in serum, yielding satisfactory validation performance. These findings support serum as a viable alternative to plasma for p-tau217 quantification in both research and clinical settings, provided matrix-specific validation is ensured.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"233 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145509215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-12DOI: 10.1093/clinchem/hvaf121
Robert L Fitzgerald,Anya Umlauf,Raymond T Suhandynata,David J Grelotti,Marilyn A Huestis,Kyle F Mastropietro,Igor Grant,Thomas D Marcotte
BACKGROUNDSeveral US states have per se laws using 2 or 5 ng/mL of delta-9-tetrahydrocannabinol (THC) as cutpoints for driving under the influence of cannabis, while some have zero-tolerance statutes. These cutpoints are considered prima facia evidence of driving impairment.METHODSIn a cohort of people who regularly use cannabis (N = 190) we measured baseline concentrations of THC after instructing participants to abstain from cannabis for at least 48 hours. Baseline driving performance was evaluated using a driving simulator. We also measured blood THC concentrations serially following a smoking session (placebo or active cannabis).RESULTSForty-three percent of the participants exceeded zero-tolerance statutes (≥0.5 ng/mL) at baseline. Twenty-four percent had baseline blood THC concentrations that were ≥2 ng/mL and 5.3% were ≥5 ng/mL. The maximum observed baseline blood concentration was 16.2 ng/mL. Six hours after smoking active cannabis, the median (interquartile range) difference in THC concentrations compared with baseline was 0.5 (0-0.9) ng/mL; a 1-sample t-test comparing the mean change to 0 was significant (P < 0.001). There was no difference when comparing the mean change to 0 in the placebo group (P = 0.69). Simulated driving performance was not different between those who exceed zero tolerance and per se cutpoints vs those who are below these cutpoints (P > 0.05).CONCLUSIONSMany regular users of cannabis exceed zero tolerance and per se THC cutpoint concentrations days after their last use, risking legal consequences despite no evidence of impairment.
{"title":"Per Se Driving Under the Influence of Cannabis Statutes and Blood Delta-9-Tetrahydrocannabinol Concentrations following Short-Term Cannabis Abstinence.","authors":"Robert L Fitzgerald,Anya Umlauf,Raymond T Suhandynata,David J Grelotti,Marilyn A Huestis,Kyle F Mastropietro,Igor Grant,Thomas D Marcotte","doi":"10.1093/clinchem/hvaf121","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf121","url":null,"abstract":"BACKGROUNDSeveral US states have per se laws using 2 or 5 ng/mL of delta-9-tetrahydrocannabinol (THC) as cutpoints for driving under the influence of cannabis, while some have zero-tolerance statutes. These cutpoints are considered prima facia evidence of driving impairment.METHODSIn a cohort of people who regularly use cannabis (N = 190) we measured baseline concentrations of THC after instructing participants to abstain from cannabis for at least 48 hours. Baseline driving performance was evaluated using a driving simulator. We also measured blood THC concentrations serially following a smoking session (placebo or active cannabis).RESULTSForty-three percent of the participants exceeded zero-tolerance statutes (≥0.5 ng/mL) at baseline. Twenty-four percent had baseline blood THC concentrations that were ≥2 ng/mL and 5.3% were ≥5 ng/mL. The maximum observed baseline blood concentration was 16.2 ng/mL. Six hours after smoking active cannabis, the median (interquartile range) difference in THC concentrations compared with baseline was 0.5 (0-0.9) ng/mL; a 1-sample t-test comparing the mean change to 0 was significant (P < 0.001). There was no difference when comparing the mean change to 0 in the placebo group (P = 0.69). Simulated driving performance was not different between those who exceed zero tolerance and per se cutpoints vs those who are below these cutpoints (P > 0.05).CONCLUSIONSMany regular users of cannabis exceed zero tolerance and per se THC cutpoint concentrations days after their last use, risking legal consequences despite no evidence of impairment.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"1 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145491481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-11DOI: 10.1093/clinchem/hvaf147
Kyla M Jorgenson, Robert A Middleberg, Brandy L Young, Alex J Krotulski, Nicholas E Nacca, Tanzy M Love, Joshua Marvald, Rachel Becker, Marilyn A Huestis, Y Victoria Zhang
Background: The increasing reports of xylazine in clinical and postmortem toxicology necessitate a survey of its clinical impact. This review examines reports of xylazine across the peer-reviewed literature and grey literature (government and public health reports).
Content: Before 2005, reports of xylazine abuse primarily involved veterinary-associated accidental and intentional exposures. A notable shift occurred in 2006 with increasing xylazine exposure documented among persons with illicit drug use, including fatal and nonfatal overdoses. Xylazine prevalence continued to increase in clinical and postmortem cases. Cases of xylazine abuse began in the northeast United States and expanded nationwide, with persistent high prevalence in the East and Midwest. Xylazine has been most frequently identified with fentanyl in clinical, drug-impaired driving, and postmortem analyses.
Summary: Xylazine's rising prevalence, especially as a fentanyl adulterant, contributes to increased opioid-related morbidity and mortality. Its presence across clinical, forensic, and environmental samples underscores the urgent need for enhanced surveillance, clinician education, public awareness, and targeted policy responses.
{"title":"Emerging Threat of Xylazine.","authors":"Kyla M Jorgenson, Robert A Middleberg, Brandy L Young, Alex J Krotulski, Nicholas E Nacca, Tanzy M Love, Joshua Marvald, Rachel Becker, Marilyn A Huestis, Y Victoria Zhang","doi":"10.1093/clinchem/hvaf147","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf147","url":null,"abstract":"<p><strong>Background: </strong>The increasing reports of xylazine in clinical and postmortem toxicology necessitate a survey of its clinical impact. This review examines reports of xylazine across the peer-reviewed literature and grey literature (government and public health reports).</p><p><strong>Content: </strong>Before 2005, reports of xylazine abuse primarily involved veterinary-associated accidental and intentional exposures. A notable shift occurred in 2006 with increasing xylazine exposure documented among persons with illicit drug use, including fatal and nonfatal overdoses. Xylazine prevalence continued to increase in clinical and postmortem cases. Cases of xylazine abuse began in the northeast United States and expanded nationwide, with persistent high prevalence in the East and Midwest. Xylazine has been most frequently identified with fentanyl in clinical, drug-impaired driving, and postmortem analyses.</p><p><strong>Summary: </strong>Xylazine's rising prevalence, especially as a fentanyl adulterant, contributes to increased opioid-related morbidity and mortality. Its presence across clinical, forensic, and environmental samples underscores the urgent need for enhanced surveillance, clinician education, public awareness, and targeted policy responses.</p>","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145488070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}