Hyun-Young Kim, Emmanuel Edward Ngasa, Hee-Jin Kim, Boram Kim, Gyujin Lim, Chang-Hun Park, Hyeon Jeong Kwon, Mi-Ae Jang, Jiyoung Woo
Background
Morphologic analysis of peripheral blood smears is essential for diagnosing hematologic diseases and patient management. Although manual microscopy is the traditional gold standard, it is time-consuming and subjective. Digital morphology analyzers have improved automation and accuracy; however, challenges remain, particularly in classifying certain cell types. Recently, the diffusion-based Wasserstein generative adversarial network with gradient penalty (DWGAN-GP) showed potential by enhancing image quality and addressing data imbalance. We aim to investigate the accuracy of blood cell classification using the DWGAN-GP model.
Methods
In this study, the DWGAN-GP model in conjunction with the EfficientNetB3 classification model was evaluated using 78,494 peripheral blood cell images. Samples were collected from patients with normal and abnormal hematologic conditions. Data were balanced by augmenting underrepresented classes with synthetic images, resulting in equal representation across 13 cell classes. Performance was compared with PBIA (ANI Co., Suwon, Korea), a commercial digital morphology analyzer.
Results
DWGAN-GP augmentation significantly improved classification accuracy of the EfficientNetB3 model to 97.74% with an F1-score of 91.13%. This result surpassed both the unbalanced dataset (accuracy 95.68%, F1-score 82.12%) and PBIA system (accuracy 95%). Notably, improvements were significant in minority classes such as blasts and myelocytes, which are critical in diagnosing leukemia.
Conclusion
Incorporating synthetic data using DWGAN-GP significantly enhanced model performance and addressed class imbalance. This method shows promise for more accurate and consistent blood cell classification, offering potential improvements in clinical diagnostics for hematologic disorders.
{"title":"Clinical Application of Using Diffusion-Based Wasserstein Generative Adversarial Network for Morphologic Analysis of Blood Cells","authors":"Hyun-Young Kim, Emmanuel Edward Ngasa, Hee-Jin Kim, Boram Kim, Gyujin Lim, Chang-Hun Park, Hyeon Jeong Kwon, Mi-Ae Jang, Jiyoung Woo","doi":"10.1002/jcla.70118","DOIUrl":"10.1002/jcla.70118","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Morphologic analysis of peripheral blood smears is essential for diagnosing hematologic diseases and patient management. Although manual microscopy is the traditional gold standard, it is time-consuming and subjective. Digital morphology analyzers have improved automation and accuracy; however, challenges remain, particularly in classifying certain cell types. Recently, the diffusion-based Wasserstein generative adversarial network with gradient penalty (DWGAN-GP) showed potential by enhancing image quality and addressing data imbalance. We aim to investigate the accuracy of blood cell classification using the DWGAN-GP model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, the DWGAN-GP model in conjunction with the EfficientNetB3 classification model was evaluated using 78,494 peripheral blood cell images. Samples were collected from patients with normal and abnormal hematologic conditions. Data were balanced by augmenting underrepresented classes with synthetic images, resulting in equal representation across 13 cell classes. Performance was compared with PBIA (ANI Co., Suwon, Korea), a commercial digital morphology analyzer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>DWGAN-GP augmentation significantly improved classification accuracy of the EfficientNetB3 model to 97.74% with an F1-score of 91.13%. This result surpassed both the unbalanced dataset (accuracy 95.68%, F1-score 82.12%) and PBIA system (accuracy 95%). Notably, improvements were significant in minority classes such as blasts and myelocytes, which are critical in diagnosing leukemia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Incorporating synthetic data using DWGAN-GP significantly enhanced model performance and addressed class imbalance. This method shows promise for more accurate and consistent blood cell classification, offering potential improvements in clinical diagnostics for hematologic disorders.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"39 22","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcla.70118","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Candida albicans exhibits significant genotypic diversity, and genotypes A and C are the most predominant clinical isolates. The aim of this study was to evaluate the virulence traits of these genotypes, focusing on exoenzyme production, biofilm formation, and cell surface hydrophobicity (CSH) property.
Methods
A total of 15 genotype A and 15 genotype C clinical C. albicans isolates were evaluated for proteinase, phospholipase, and esterase activities using standard methods. Biofilm formation was quantified using a microtiter plate assay, and CSH was measured using a water-octane two-phase assay.
Results
The study found that Genotype C had higher proteinase and phospholipase activity but no esterase production, while 40% of Genotype A isolates showed strong esterase activity. Biofilm formation and CSH did not differ significantly, though Genotype A trended toward stronger biofilm formation.
Conclusion
This study highlights how genotypic variation in C. albicans influences virulence, with Genotype C exhibiting a distinct profile (high proteinase/phospholipase, no esterase) that may enhance pathogenicity, while Genotype A shows adaptability through variable enzyme production and stronger biofilm trends. These differences underscore the need for genotype-specific diagnostics and targeted therapies to improve candidiasis treatment.
{"title":"A Comparative Evaluation of Exoenzyme Production, Biofilm Development, and Cell Surface Hydrophobicity in Dominant Genotypes of Candida albicans","authors":"Hasti Nouraei, Neda Amirzadeh, Fatemeh Ahmadi, Keyvan Pakshir","doi":"10.1002/jcla.70115","DOIUrl":"10.1002/jcla.70115","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p><i>Candida albicans</i> exhibits significant genotypic diversity, and genotypes A and C are the most predominant clinical isolates. The aim of this study was to evaluate the virulence traits of these genotypes, focusing on exoenzyme production, biofilm formation, and cell surface hydrophobicity (CSH) property.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 15 genotype A and 15 genotype C clinical <i>C. albicans</i> isolates were evaluated for proteinase, phospholipase, and esterase activities using standard methods. Biofilm formation was quantified using a microtiter plate assay, and CSH was measured using a water-octane two-phase assay.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study found that Genotype C had higher proteinase and phospholipase activity but no esterase production, while 40% of Genotype A isolates showed strong esterase activity. Biofilm formation and CSH did not differ significantly, though Genotype A trended toward stronger biofilm formation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study highlights how genotypic variation in <i>C. albicans</i> influences virulence, with Genotype C exhibiting a distinct profile (high proteinase/phospholipase, no esterase) that may enhance pathogenicity, while Genotype A shows adaptability through variable enzyme production and stronger biofilm trends. These differences underscore the need for genotype-specific diagnostics and targeted therapies to improve candidiasis treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"39 22","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcla.70115","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p>We read with great interest the study by Lutfi et al., which represents the first region-specific attempt to establish hematological reference intervals (RIs) in Northern Sudan [<span>1</span>]. The authors' rigorous field-based methodology and stratification by gender within a reasonably powered sample is commendable. However, several analytical, interpretive, and generalizability-related issues warrant attention.</p><p>First, while the study adhered to the Clinical and Laboratory Standards Institute (CLSI) recommendations for a minimum of 120 participants per subgroup, no power calculation was presented to justify the sufficiency of subgroup-specific sample sizes (e.g., females, <i>n</i> = 112). Considering that the study also conducted gender-wise comparisons for 13 hematological indices, the absence of a Bonferroni correction or other method to adjust for multiple comparisons increases the risk of Type I error [<span>2</span>]. This is particularly concerning, given the borderline significance of several findings (e.g., PDW: <i>p</i> = 0.021; MPV: <i>p</i> = 0.021).</p><p>Second, the use of the Mann–Whitney <i>U</i> test to compare medians was appropriate due to non-normal data distribution. However, the authors did not explore potential confounding factors that could influence hematological values, such as BMI, marital status, educational attainment, or occupational status [<span>3-5</span>], variables that were collected but not statistically modeled. Multivariable regression or stratified analyses could offer more nuanced insights, particularly given the observed sociodemographic heterogeneity.</p><p>Third, while the study excluded individuals with chronic illnesses and recent infections, reliance solely on self-report and observational screening without confirmatory laboratory diagnostics (e.g., stool microscopy for helminths, serum ferritin for iron status, and hemoglobin electrophoresis for hemoglobinopathies) raises concerns about subclinical confounders. Given the high endemicity of iron-deficiency anemia and sickle cell trait in Northern Africa [<span>6</span>], the established RIs may have inadvertently incorporated pathological values, thereby underestimating true physiological norms.</p><p>Fourth, the study's comparison with previous RI studies from other Sudanese regions and neighboring countries offers a useful context but fails to systematically account for methodological heterogeneity. For instance, variations in analyzer types, calibration standards, sample handling time, and altitude-related hypoxia could significantly impact parameters such as hemoglobin and RBC count [<span>7</span>]. Without standardizing these variables, direct cross-country RI comparisons may yield misleading conclusions.</p><p>Fifth, the inclusion of only one district (Wad Hamid) restricted extrapolation. The authors correctly noted ethnic and environmental diversity across the River Nile, but the study's design did not capture this intra-regional v
我们怀着极大的兴趣阅读了Lutfi等人的研究，这是在苏丹北部地区首次尝试建立血液学参考区间（RIs）。作者严格的基于实地的方法和在合理有力的样本中按性别分层是值得称赞的。然而，有几个与分析、解释和概括性有关的问题值得注意。首先，虽然该研究遵循临床和实验室标准协会（CLSI）的建议，每个亚组至少有120名参与者，但没有提出功率计算来证明亚组特定样本量的充分性（例如，女性，n = 112）。考虑到本研究还对13项血液学指标进行了性别比较，缺乏Bonferroni校正或其他方法来调整多重比较，增加了I型误差[2]的风险。考虑到几个结果的临界意义（例如，PDW: p = 0.021; MPV: p = 0.021），这一点尤其令人担忧。其次，由于非正态数据分布，使用Mann-Whitney U检验比较中位数是合适的。然而，作者没有探索可能影响血液学值的潜在混杂因素，如BMI、婚姻状况、受教育程度或职业状况[3-5]，这些变量是收集的，但没有进行统计建模。多变量回归或分层分析可以提供更细致入微的见解，特别是考虑到观察到的社会人口异质性。第三，虽然该研究排除了患有慢性疾病和近期感染的个体，但仅依靠自我报告和观察性筛查而没有确认的实验室诊断（例如，粪便显微镜检查蠕虫，血清铁蛋白检查铁状态，血红蛋白电泳检查血红蛋白病）引起了对亚临床混杂因素的担忧。鉴于缺铁性贫血和镰状细胞特征在北非地区的高地方性，已建立的RIs可能在不经意间纳入了病理学值，从而低估了真实的生理标准。第四，该研究与其他苏丹地区和邻国以前的国际扶轮研究的比较提供了一个有用的背景，但未能系统地解释方法的异质性。例如，分析仪类型、校准标准、样品处理时间的变化以及与海拔相关的缺氧都会显著影响血红蛋白和红细胞计数等参数。如果不将这些变量标准化，直接的跨国国际指数比较可能会产生误导性的结论。第五，仅纳入一个地区（瓦德哈米德）限制了外推。作者正确地指出了尼罗河两岸的种族和环境多样性，但是这项研究的设计并没有捕捉到这种区域内的可变性。此外，尽管收集了连续的年龄数据，但缺乏年龄分层的RIs，限制了其在老年或年轻成人亚组的临床解释的实用性。最后，尽管血液学参数的性别差异具有统计学意义，但其临床相关性仍然不明确。例如，男性（14.1 g/dL）和女性（12.5 g/dL）的血红蛋白中位数在广泛接受的正常范围内，但缺乏关于诊断阈值或错误分类风险的讨论，降低了翻译价值。总之，虽然本研究提供了基础的区域数据，但未来的研究应纳入更广泛的采样框架、亚临床条件的生化验证、混杂因素调整模型和年龄特异性RIs。这些改进可大大提高北部苏丹血液学基准的临床适用性，并促进将其纳入国家诊断方案。Rachana Mehta：写作-原稿，写作-审查和编辑。Ranjana Sah：概念化，方法论，验证，监督，项目管理，写作-原稿，写作-审查和编辑。生成式人工智能工具，包括Paperpal和chatgpt - 40，仅用于语言，语法和风格改进。这些工具在本文的概念化、数据分析、结果解释或实质性内容开发中没有作用。所有的智力贡献，数据分析和科学解释仍然是作者的唯一工作。最后的内容经过严格审查和编辑，以确保准确性和原创性。作者对文章的准确性、原创性和完整性承担全部责任。不适用，因为本研究未收集或分析患者数据。作者声明无利益冲突。不适用，因为本研究没有生成或分析数据。
{"title":"Comment on “Reference Intervals of Hematological Parameters Among Healthy Adults in Northern Sudan: A Community-Based Cross-Sectional Study”","authors":"Rachana Mehta, Ranjana Sah","doi":"10.1002/jcla.70121","DOIUrl":"10.1002/jcla.70121","url":null,"abstract":"<p>We read with great interest the study by Lutfi et al., which represents the first region-specific attempt to establish hematological reference intervals (RIs) in Northern Sudan [<span>1</span>]. The authors' rigorous field-based methodology and stratification by gender within a reasonably powered sample is commendable. However, several analytical, interpretive, and generalizability-related issues warrant attention.</p><p>First, while the study adhered to the Clinical and Laboratory Standards Institute (CLSI) recommendations for a minimum of 120 participants per subgroup, no power calculation was presented to justify the sufficiency of subgroup-specific sample sizes (e.g., females, <i>n</i> = 112). Considering that the study also conducted gender-wise comparisons for 13 hematological indices, the absence of a Bonferroni correction or other method to adjust for multiple comparisons increases the risk of Type I error [<span>2</span>]. This is particularly concerning, given the borderline significance of several findings (e.g., PDW: <i>p</i> = 0.021; MPV: <i>p</i> = 0.021).</p><p>Second, the use of the Mann–Whitney <i>U</i> test to compare medians was appropriate due to non-normal data distribution. However, the authors did not explore potential confounding factors that could influence hematological values, such as BMI, marital status, educational attainment, or occupational status [<span>3-5</span>], variables that were collected but not statistically modeled. Multivariable regression or stratified analyses could offer more nuanced insights, particularly given the observed sociodemographic heterogeneity.</p><p>Third, while the study excluded individuals with chronic illnesses and recent infections, reliance solely on self-report and observational screening without confirmatory laboratory diagnostics (e.g., stool microscopy for helminths, serum ferritin for iron status, and hemoglobin electrophoresis for hemoglobinopathies) raises concerns about subclinical confounders. Given the high endemicity of iron-deficiency anemia and sickle cell trait in Northern Africa [<span>6</span>], the established RIs may have inadvertently incorporated pathological values, thereby underestimating true physiological norms.</p><p>Fourth, the study's comparison with previous RI studies from other Sudanese regions and neighboring countries offers a useful context but fails to systematically account for methodological heterogeneity. For instance, variations in analyzer types, calibration standards, sample handling time, and altitude-related hypoxia could significantly impact parameters such as hemoglobin and RBC count [<span>7</span>]. Without standardizing these variables, direct cross-country RI comparisons may yield misleading conclusions.</p><p>Fifth, the inclusion of only one district (Wad Hamid) restricted extrapolation. The authors correctly noted ethnic and environmental diversity across the River Nile, but the study's design did not capture this intra-regional v","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"39 23","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcla.70121","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mohammad Darvishi, Mohammad Mahdi Heidari, Reza Kheradmand, Nava Moghadasian Niaki, Mahsa Tabean, Ahmad Mobed
Objective
This study investigates the innovative application of nanomaterial-based micro-devices aimed at enhancing the diagnosis and management of acyclovir (ACV) for herpes virus infections, specifically those caused by HSV-1, HSV-2, CMV, and VZV.
Background
Herpes viruses are associated with various clinical diseases, highlighting the urgent need for effective antiviral therapies. Acyclovir remains a primary treatment option; however, its potential for kidney toxicity and allergic reactions necessitates careful dosage monitoring, particularly in immunocompromised patients.
Methods
Recent advancements in drug monitoring systems have been developed to optimize dosing regimens and reduce the risk of misuse. This study focuses on the integration of biological and electrochemical nanosensors utilizing nanomaterials, which have shown significant improvements in detection capabilities and diagnostic sensitivity for ACV.
Results
We delineate the novel features and applications of these micro-devices, emphasizing their unique configurations and unprecedented limits of detection.
Conclusion
This research illustrates how these advanced technologies can enhance existing methodologies in herpes virus management, ultimately leading to improved treatment outcomes.
{"title":"Nanomaterial-Enhanced Electrochemical Sensors for Clinical Monitoring of Acyclovir: Integration Into Molecular Diagnostics","authors":"Mohammad Darvishi, Mohammad Mahdi Heidari, Reza Kheradmand, Nava Moghadasian Niaki, Mahsa Tabean, Ahmad Mobed","doi":"10.1002/jcla.70104","DOIUrl":"10.1002/jcla.70104","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study investigates the innovative application of nanomaterial-based micro-devices aimed at enhancing the diagnosis and management of acyclovir (ACV) for herpes virus infections, specifically those caused by HSV-1, HSV-2, CMV, and VZV.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Herpes viruses are associated with various clinical diseases, highlighting the urgent need for effective antiviral therapies. Acyclovir remains a primary treatment option; however, its potential for kidney toxicity and allergic reactions necessitates careful dosage monitoring, particularly in immunocompromised patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Recent advancements in drug monitoring systems have been developed to optimize dosing regimens and reduce the risk of misuse. This study focuses on the integration of biological and electrochemical nanosensors utilizing nanomaterials, which have shown significant improvements in detection capabilities and diagnostic sensitivity for ACV.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We delineate the novel features and applications of these micro-devices, emphasizing their unique configurations and unprecedented limits of detection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This research illustrates how these advanced technologies can enhance existing methodologies in herpes virus management, ultimately leading to improved treatment outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"39 20","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcla.70104","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The present study aimed to investigate the association between vitamin D receptor (VDR) FokI gene variants and the risk of type 2 diabetes mellitus (T2DM) and its complications, as well as with oxidative stress parameters.
Methods
We investigated 300 individuals with diabetes with and without neuropathy and retinopathy, and 100 individuals without diabetes. The PCR-RFLP technique was used to determine the genotypes of VDR FokI T>C (rs2228570). The oxidative stress parameters were measured using chemical methods.
Results
In individuals with diabetes, there were significantly higher levels of body mass index (BMI) and oxidative stress than in controls. The presence of the FokI CC genotype and the C allele were associated with 2.46 times and 1.6-fold increased risk of T2DM, respectively, and enhanced diabetic neuropathy risk by 3.41- and 3.68-fold, respectively, and elevated diabetic retinopathy risk by 2.45 and 1.59 times, respectively. The presence of FokI TC + CC compared to the TT genotype resulted in higher triglycerides, total oxidative status, and BMI levels in individuals with diabetes. We found significantly higher BMI, oxidative stress index, and significantly lower levels of total antioxidant capacity in females than in males among individuals with diabetes and controls.
Conclusion
This study indicates that the FokI CC genotype and the FokI C allele are associated with an increased risk of T2DM and its complications. We observed the influence of VDR FokI variants on dyslipidemia, oxidative stress, and BMI. It seems the risk factors of developing T2DM, obesity, and oxidative stress among women are more prevalent than in men.
{"title":"The Association of VDR FokI T>C (rs2228570) Gene Variants With T2DM, and Its Complications: Influence on BMI, Oxidative Stress, and Dyslipidemia","authors":"Armin Sharifi, Mahsa Nouri, Ebrahim Shakiba, Zahra Ghorbani, Zohreh Rahimi","doi":"10.1002/jcla.70090","DOIUrl":"10.1002/jcla.70090","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The present study aimed to investigate the association between vitamin D receptor (VDR) <i>FokI</i> gene variants and the risk of type 2 diabetes mellitus (T2DM) and its complications, as well as with oxidative stress parameters.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We investigated 300 individuals with diabetes with and without neuropathy and retinopathy, and 100 individuals without diabetes. The PCR-RFLP technique was used to determine the genotypes of VDR <i>FokI</i> T>C (rs2228570). The oxidative stress parameters were measured using chemical methods.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In individuals with diabetes, there were significantly higher levels of body mass index (BMI) and oxidative stress than in controls. The presence of the FokI CC genotype and the C allele were associated with 2.46 times and 1.6-fold increased risk of T2DM, respectively, and enhanced diabetic neuropathy risk by 3.41- and 3.68-fold, respectively, and elevated diabetic retinopathy risk by 2.45 and 1.59 times, respectively. The presence of FokI TC + CC compared to the TT genotype resulted in higher triglycerides, total oxidative status, and BMI levels in individuals with diabetes. We found significantly higher BMI, oxidative stress index, and significantly lower levels of total antioxidant capacity in females than in males among individuals with diabetes and controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study indicates that the <i>FokI</i> CC genotype and the <i>FokI</i> C allele are associated with an increased risk of T2DM and its complications. We observed the influence of VDR <i>FokI</i> variants on dyslipidemia, oxidative stress, and BMI. It seems the risk factors of developing T2DM, obesity, and oxidative stress among women are more prevalent than in men.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"39 19","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcla.70090","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lingde Shen, Yuanfang Lin, Weifeng Chen, Dan Zhou, Hui Peng
Background
The purpose of this research is to investigate the particular connection between the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and non-alcoholic fatty liver disease (NAFLD) to offer a more precise foundation for evaluating NAFLD risk.
Methods
This study involves a secondary analysis of a retrospective cohort study conducted from 2004 to 2015 in a Japanese population, which included 14,106 participants. The TG/HDL-C ratio was determined by the levels of triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C). Participants were grouped according to the quartiles of TG/HDL-C. We analyzed the relationship between TG/HDL-C and NAFLD using Cox proportional hazards regression, smooth curve fitting, and sensitivity analysis.
Results
The average age of the study participants was 43.51 ± 8.89 years, with 7275 (51.57%) being male. After considering potential confounding factors, the study found a positive correlation between TG/HDL-C and NAFLD (OR: 1.37, 95% CI: 1.31–1.43, p < 0.001). Moreover, a nonlinear relationship between TG/HDL-C and NAFLD was found, with a turning point at 1.42. The odds ratio (OR) on either side of this inflection point were 3.71 (95% CI: 2.87–4.79) on the left and 1.23 (95% CI: 1.17–1.29) on the right, indicating a stronger correlation when TG/HDL-C is below 1.42, particularly in younger individuals, females, and those with a BMI under 25 kg/m2.
Conclusion
The TG/HDL-C index shows a nonlinear positive correlation with NAFLD risk, particularly when the TG/HDL-C ratio is below 1.42, with a stronger association observed in younger individuals, females, and lower-BMI populations.
背景：本研究的目的是探讨甘油三酯与高密度脂蛋白胆固醇（TG/HDL-C）比值与非酒精性脂肪性肝病（NAFLD）之间的特殊关系，为评估NAFLD风险提供更精确的基础。方法：本研究对2004年至2015年在日本人群中进行的回顾性队列研究进行了二次分析，其中包括14106名参与者。TG/HDL-C比值由甘油三酯（TG）和高密度脂蛋白胆固醇（HDL-C）水平决定。参与者根据TG/HDL-C的四分位数分组。我们使用Cox比例风险回归、平滑曲线拟合和敏感性分析分析TG/HDL-C与NAFLD之间的关系。结果：研究对象平均年龄43.51±8.89岁，男性7275人（51.57%）。在考虑了潜在的混杂因素后，研究发现TG/HDL-C与NAFLD呈正相关（OR: 1.37, 95% CI: 1.31-1.43, p 2）。结论：TG/HDL-C指数与NAFLD风险呈非线性正相关，特别是当TG/HDL-C比值低于1.42时，在年轻个体、女性和低bmi人群中观察到更强的相关性。
{"title":"Nonlinear Relationship Between Triglyceride-to-High-Density Lipoprotein Cholesterol Ratio and Non-Alcoholic Fatty Liver Disease: A Secondary Retrospective Analysis Based on a Japanese Longitudinal Study","authors":"Lingde Shen, Yuanfang Lin, Weifeng Chen, Dan Zhou, Hui Peng","doi":"10.1002/jcla.70107","DOIUrl":"10.1002/jcla.70107","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The purpose of this research is to investigate the particular connection between the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and non-alcoholic fatty liver disease (NAFLD) to offer a more precise foundation for evaluating NAFLD risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study involves a secondary analysis of a retrospective cohort study conducted from 2004 to 2015 in a Japanese population, which included 14,106 participants. The TG/HDL-C ratio was determined by the levels of triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C). Participants were grouped according to the quartiles of TG/HDL-C. We analyzed the relationship between TG/HDL-C and NAFLD using Cox proportional hazards regression, smooth curve fitting, and sensitivity analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The average age of the study participants was 43.51 ± 8.89 years, with 7275 (51.57%) being male. After considering potential confounding factors, the study found a positive correlation between TG/HDL-C and NAFLD (OR: 1.37, 95% CI: 1.31–1.43, <i>p</i> < 0.001). Moreover, a nonlinear relationship between TG/HDL-C and NAFLD was found, with a turning point at 1.42. The odds ratio (OR) on either side of this inflection point were 3.71 (95% CI: 2.87–4.79) on the left and 1.23 (95% CI: 1.17–1.29) on the right, indicating a stronger correlation when TG/HDL-C is below 1.42, particularly in younger individuals, females, and those with a BMI under 25 kg/m<sup>2</sup>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The TG/HDL-C index shows a nonlinear positive correlation with NAFLD risk, particularly when the TG/HDL-C ratio is below 1.42, with a stronger association observed in younger individuals, females, and lower-BMI populations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"39 20","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcla.70107","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Manqing Nie, Hang Du, Tiancheng Xie, Bo Zheng, Xiaoli Zou, Guokang Sun, Qiurong He, Ling Wu, Jing Zhang, Dingzi Zhou
Background
Environmental metal pollution poses a potential threat to public health, and reference intervals (RIs) are crucial tools for assessing exposure levels.
Aims
Our study was the first to systematically establish RIs for lead, arsenic, mercury, and cadmium in a population in southwest China, examining differences across genders and ages. The study also compared the differences between RIs obtained by two sampling techniques, including direct and indirect sampling, to assess the substitutability and limitations between the two techniques.
Materials and Methods
Direct sampling employed atomic absorption spectrometry (AAS) and inductively coupled plasma-mass spectrometry (ICP-MS) on human biomonitoring (HBM) data, while indirect sampling utilized a Gaussian Mixture Model (GMM) applied to a local Laboratory Information System (LIS) database. RIs were determined using the nonparametric method for both approaches.
Results
RIs were established for each metal, with variations observed across age groups for cadmium and lead, and across genders for lead in certain age groups. Most of the RIs established by the direct sampling technique had a narrower range compared to that established by GMM, and the RIs established by the two techniques were partially biased.
Discussion and Conclusion
These RIs offer a vital baseline for assessing environmental metal exposure and identifying metal poisoning in Southwest China. Additionally, this study highlights the potential of the GMM-based indirect sampling technique as a viable alternative to the traditional direct sampling technique, with the dual-technique comparison enhancing our understanding of their substitutability and limitations, thus opening new avenues for environmental health research.
{"title":"Reference Intervals for Lead, Arsenic, Mercury, and Cadmium in the Population of Southwest China: A Comparative Study of Direct and Indirect Sampling Techniques","authors":"Manqing Nie, Hang Du, Tiancheng Xie, Bo Zheng, Xiaoli Zou, Guokang Sun, Qiurong He, Ling Wu, Jing Zhang, Dingzi Zhou","doi":"10.1002/jcla.70096","DOIUrl":"10.1002/jcla.70096","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Environmental metal pollution poses a potential threat to public health, and reference intervals (RIs) are crucial tools for assessing exposure levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Our study was the first to systematically establish RIs for lead, arsenic, mercury, and cadmium in a population in southwest China, examining differences across genders and ages. The study also compared the differences between RIs obtained by two sampling techniques, including direct and indirect sampling, to assess the substitutability and limitations between the two techniques.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Direct sampling employed atomic absorption spectrometry (AAS) and inductively coupled plasma-mass spectrometry (ICP-MS) on human biomonitoring (HBM) data, while indirect sampling utilized a Gaussian Mixture Model (GMM) applied to a local Laboratory Information System (LIS) database. RIs were determined using the nonparametric method for both approaches.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>RIs were established for each metal, with variations observed across age groups for cadmium and lead, and across genders for lead in certain age groups. Most of the RIs established by the direct sampling technique had a narrower range compared to that established by GMM, and the RIs established by the two techniques were partially biased.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion and Conclusion</h3>\u0000 \u0000 <p>These RIs offer a vital baseline for assessing environmental metal exposure and identifying metal poisoning in Southwest China. Additionally, this study highlights the potential of the GMM-based indirect sampling technique as a viable alternative to the traditional direct sampling technique, with the dual-technique comparison enhancing our understanding of their substitutability and limitations, thus opening new avenues for environmental health research.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"39 19","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcla.70096","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Globally, multidrug resistance (MDR), including extended-spectrum β-lactamase (ESBL) and carbapenemase production in Enterobacteriaceae, is increasing. Data concerning their presence in South Lebanon are scarce. This study aimed to determine the prevalence of ESBL and carbapenem-resistant Enterobacteriaceae (CRE) in Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) isolates from the Saida region.
Methods
In Hammoud Hospital University Medical Center (HHUMC), and over a period of 9 months, identification and susceptibility testing of the isolates using the Kirby–Bauer method were performed and then confirmed as recommended by the Clinical and Laboratory Standards Institute (CLSI). Molecular analysis of the genes encoding ESBL and carbapenemases was investigated by polymerase chain reaction (PCR).
Results
A total of 200 isolates (171 E. coli and 29 K. pneumoniae) were obtained from different clinical specimens (urine, rectal swabs, blood, sputum, pus, wound/tissue, nasal swabs, vaginal swabs) and were subsequently studied. Nearly 89.5% (179/200) and 10.5% (21/200) of the isolates were producers of ESBL and carbapenemase, respectively. The ESBL isolates showed high sensitivity toward carbapenem drugs, whereas the CRE isolates were most sensitive to tigecycline. Of 67 studied ESBL isolates, blaCTX-M (44.8%) was the most prevalent gene, followed by blaTEM (37.3%) and blaSHV (13.4%). Among the CRE isolates, only two of 21 collected isolates were positive for the blaOXA-48 gene.
Conclusion
This type of scenario highlights the necessity of using antibiotics sparingly and putting stringent measures in place to prevent infections.
{"title":"Phenotypic, Targeted Genotypic, and Antimicrobial Susceptibility Profiling of Extended-Spectrum β-Lactamase Production and Exclusive blaOXA−48 Gene Detection in Escherichia coli and Klebsiella pneumoniae Isolates From a South Lebanese Hospital","authors":"Aya Kahil, Elie Salem Sokhn","doi":"10.1002/jcla.70108","DOIUrl":"10.1002/jcla.70108","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Globally, multidrug resistance (MDR), including extended-spectrum β-lactamase (ESBL) and carbapenemase production in <i>Enterobacteriaceae</i>, is increasing. Data concerning their presence in South Lebanon are scarce. This study aimed to determine the prevalence of ESBL and carbapenem-resistant <i>Enterobacteriaceae</i> (CRE) in <i>Escherichia coli</i> (<i>E. coli</i>) and <i>Klebsiella pneumoniae</i> (<i>K. pneumoniae</i>) isolates from the Saida region.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In Hammoud Hospital University Medical Center (HHUMC), and over a period of 9 months, identification and susceptibility testing of the isolates using the Kirby–Bauer method were performed and then confirmed as recommended by the Clinical and Laboratory Standards Institute (CLSI). Molecular analysis of the genes encoding ESBL and carbapenemases was investigated by polymerase chain reaction (PCR).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 200 isolates (171 <i>E. coli</i> and 29 <i>K. pneumoniae</i>) were obtained from different clinical specimens (urine, rectal swabs, blood, sputum, pus, wound/tissue, nasal swabs, vaginal swabs) and were subsequently studied. Nearly 89.5% (179/200) and 10.5% (21/200) of the isolates were producers of ESBL and carbapenemase, respectively. The ESBL isolates showed high sensitivity toward carbapenem drugs, whereas the CRE isolates were most sensitive to tigecycline. Of 67 studied ESBL isolates, <i>bla</i><sub>CTX-M</sub> (44.8%) was the most prevalent gene, followed by <i>bla</i><sub>TEM</sub> (37.3%) and <i>bla</i><sub>SHV</sub> (13.4%). Among the CRE isolates, only two of 21 collected isolates were positive for the <i>bla</i><sub>OXA-48</sub> gene.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This type of scenario highlights the necessity of using antibiotics sparingly and putting stringent measures in place to prevent infections.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"39 20","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcla.70108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Francesco Janes, Paola Dalla Siega, Marco Comar, Matteo Furlani, Agnese Zanus Fortes, Daniela Visentini, Andrea Ripoli, Francesco Sbrana, Novella Carannante, Silvia Leonardi, Francesco Curcio, Mariarosaria Valente, Martina Fabris, Carlo Tascini
Objectives
Despite numerous pieces of evidence of its important role as a diagnostic and prognostic biomarker in infectious diseases and sepsis, adrenomedullin (ADM) was only poorly investigated in cerebrospinal fluid (CSF) in central nervous system (CNS) infections. In this multicentre retrospective study, we investigated ADM CSF concentrations in acute meningitis compared to other noninfectious neurological disorders.
Methods
Since ADM is rapidly metabolised in vivo, the available diagnostic methods are designed to measure its cognate metabolite called mid-regional proADM (MR-proADM). We collected detailed clinical and laboratory data about 293 patients in whom MR-proADM was measured in CSF and plasma as part of the diagnostic workup.
Results
Patients were finally classified in CNS infection (n = 59), other CNS disorders (n = 190) and 14 disease controls, in which CNS infections and other definite disorders were excluded. Both cerebrospinal MR-proADM levels and their CSF/blood ratio were significantly higher in CNS infections compared to the other two groups (p < 0.001 and p < 0.037 respectively). CSF MR-proADM resulted informative for patients' classification, furnishing a volume under the ROC surface of 0.513 [0.414–0.613], overcoming the 1/6 threshold value for undecidability. Threshold values of < 0.807 and > 1.590 nmol/L can differentiate controls from neurological disorders and neurological disorders from CNS infections respectively.
Conclusions
We demonstrated significant upregulation of Adrenomedullin in CSF during infections compared to other neurological diseases and proposed preliminary thresholds of CSF MR-proADM to be used in the diagnostic workup of acute CNS infections, to help with differential diagnosis and possibly guide targeted therapeutic interventions.
{"title":"Mid-Regional Proadrenomedullin in Cerebrospinal Fluid Is a Reliable Diagnostic and Prognostic Marker for Acute Meningoencephalitis and Neurological Disorders","authors":"Francesco Janes, Paola Dalla Siega, Marco Comar, Matteo Furlani, Agnese Zanus Fortes, Daniela Visentini, Andrea Ripoli, Francesco Sbrana, Novella Carannante, Silvia Leonardi, Francesco Curcio, Mariarosaria Valente, Martina Fabris, Carlo Tascini","doi":"10.1002/jcla.70110","DOIUrl":"10.1002/jcla.70110","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Despite numerous pieces of evidence of its important role as a diagnostic and prognostic biomarker in infectious diseases and sepsis, adrenomedullin (ADM) was only poorly investigated in cerebrospinal fluid (CSF) in central nervous system (CNS) infections. In this multicentre retrospective study, we investigated ADM CSF concentrations in acute meningitis compared to other noninfectious neurological disorders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Since ADM is rapidly metabolised in vivo, the available diagnostic methods are designed to measure its cognate metabolite called mid-regional proADM (MR-proADM). We collected detailed clinical and laboratory data about 293 patients in whom MR-proADM was measured in CSF and plasma as part of the diagnostic workup.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients were finally classified in CNS infection (<i>n</i> = 59), other CNS disorders (<i>n</i> = 190) and 14 disease controls, in which CNS infections and other definite disorders were excluded. Both cerebrospinal MR-proADM levels and their CSF/blood ratio were significantly higher in CNS infections compared to the other two groups (<i>p</i> < 0.001 and <i>p</i> < 0.037 respectively). CSF MR-proADM resulted informative for patients' classification, furnishing a volume under the ROC surface of 0.513 [0.414–0.613], overcoming the 1/6 threshold value for undecidability. Threshold values of < 0.807 and > 1.590 nmol/L can differentiate controls from neurological disorders and neurological disorders from CNS infections respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We demonstrated significant upregulation of Adrenomedullin in CSF during infections compared to other neurological diseases and proposed preliminary thresholds of CSF MR-proADM to be used in the diagnostic workup of acute CNS infections, to help with differential diagnosis and possibly guide targeted therapeutic interventions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"39 20","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcla.70110","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Can Liu, Yupeng Song, Siyan Niu, Yili Jiang, Tingting Zhu, Xin Li, Rui Cui, Qi Deng
Background
Hematologic malignancy patients with B lymphocytopenia after anti-CD20 monoclonal antibody or anti-CD19 chimeric antigen receptor (CAR) T cell therapy often face prolonged SARS-CoV-2 positivity on pharyngeal swabs and persistent or recurrent COVID-19 infection, resulting in high mortality.
Methods
Here, we describe three follicular lymphoma (FL) patients with persistent fever, cough, and hypoxemia, but they were ruled out for bacterial, viral, fungal, and other pathogen infections, and the throat swabs were consistently SARS-CoV-2 negative. These FL patients with B lymphocyte deficiency who were diagnosed with COVID-19 infection confirmed by bronchoalveolar lavage fluid (BALF) metagenomics next-generation sequencing (mNGS). Their COVID-19 infection was characterized by differences in viral load in the upper and lower respiratory tracts. When this particular COVID-19 infection occurred, although their percentages and absolute values of CD8+ T cells and CD4+ T cells were normal, they all had B lymphocyte deficiency and hypogammaglobulinemia. They all had low expression of interleukin (IL)-6 in peripheral blood inconsistent with clinical infection symptoms.
Results
The patients received a combination therapy of molnupiravir and methylprednisolone; then their symptoms were relieved over the next 2 weeks–2 months.
Conclusion
Therefore, for immunocompromised patients, especially those with B lymphocyte deficiency, hypogammaglobulinemia, and low expression of IL-6 in peripheral blood inconsistent with clinical infection symptoms, mNGS for BALF should be performed as soon as possible in this particular condition to confirm the diagnosis of COVID-19 infection.
{"title":"COVID-19 Infection Confirmed by Bronchoalveolar Lavage Fluid Metagenomics -Next-Generation Sequencing Instead of Pharyngeal Swabs in Follicular Lymphoma: Three-Case Report and Literature Review","authors":"Can Liu, Yupeng Song, Siyan Niu, Yili Jiang, Tingting Zhu, Xin Li, Rui Cui, Qi Deng","doi":"10.1002/jcla.70103","DOIUrl":"10.1002/jcla.70103","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hematologic malignancy patients with B lymphocytopenia after anti-CD20 monoclonal antibody or anti-CD19 chimeric antigen receptor (CAR) T cell therapy often face prolonged SARS-CoV-2 positivity on pharyngeal swabs and persistent or recurrent COVID-19 infection, resulting in high mortality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Here, we describe three follicular lymphoma (FL) patients with persistent fever, cough, and hypoxemia, but they were ruled out for bacterial, viral, fungal, and other pathogen infections, and the throat swabs were consistently SARS-CoV-2 negative. These FL patients with B lymphocyte deficiency who were diagnosed with COVID-19 infection confirmed by bronchoalveolar lavage fluid (BALF) metagenomics next-generation sequencing (mNGS). Their COVID-19 infection was characterized by differences in viral load in the upper and lower respiratory tracts. When this particular COVID-19 infection occurred, although their percentages and absolute values of CD8<sup>+</sup> T cells and CD4<sup>+</sup> T cells were normal, they all had B lymphocyte deficiency and hypogammaglobulinemia. They all had low expression of interleukin (IL)-6 in peripheral blood inconsistent with clinical infection symptoms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The patients received a combination therapy of molnupiravir and methylprednisolone; then their symptoms were relieved over the next 2 weeks–2 months.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Therefore, for immunocompromised patients, especially those with B lymphocyte deficiency, hypogammaglobulinemia, and low expression of IL-6 in peripheral blood inconsistent with clinical infection symptoms, mNGS for BALF should be performed as soon as possible in this particular condition to confirm the diagnosis of COVID-19 infection.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"39 20","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcla.70103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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