Journal of Clinical Laboratory Analysis最新文献

{"title":"Enhanced Commendable Sensitivity and Specificity for MSI in Colorectal Cancer by a New PCR-HRM Based 8-Loci MSI Assay","authors":"Xueping Xiang,&nbsp;Xiaojing Ma,&nbsp;Linlin Ying,&nbsp;Hong Zou","doi":"10.1002/jcla.25085","DOIUrl":"10.1002/jcla.25085","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>This study evaluated the performance of the PCR-HRM assay by comparing it with immunohistochemistry (IHC) for mismatch repair (MMR) proteins and the PCR capillary electrophoresis (PCR-CE) methods.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 224 patients with colorectal cancer participated in the study, with nearly half having mismatch repair deficiency (dMMR) tissues and the remainder possessing pMMR tissues. There was a 97.77% concordance between the PCR-HRM assay and IHC, and a 97.56% concordance between PCR-HRM and the PCR-CE assay. In comparison with IHC for dMMR proteins, the PCR-HRM demonstrated a sensitivity of 96.36% and a specificity of 99.12%. When juxtaposed with the PCR-CE assay, its sensitivity was 98.96% and specificity stood at 96.33%. The mutations observed in the microsatellite loci were uniformly distributed across all eight loci. Discrepant outcomes were more frequent in instances of MLH1 and PMS2 deficiency. Furthermore, the germline mutation status of MLH1, MSH2, PMS2, and MSH6 in 62 patients was ascertained using next-generation sequencing. All patients displaying MMR gene pathogenic mutations (<i>N</i> = 14) were identified as MSI-H by PCR-HRM, whereas those with MSS tissues (<i>N</i> = 43) did not exhibit MMR gene pathogenic mutations. Thus, the PCR-HRM method proficiently pinpoints tumors with verified germline MMR mutations, indicative of Lynch syndrome.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Conclusively, the PCR-HRM assay emerges as a swift and congruent diagnostic tool for microsatellite instability, boasting commendable sensitivity and specificity in colorectal cancer.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"38 15-16","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcla.25085","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916861","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}

{"title":"Changes in Red Cell Morphology and Haematological Laboratory Parameters Associated With Alectinib","authors":"Ting Hon Stanford Li,&nbsp;Yin Kwan Jeannie Chik,&nbsp;Ka Yan Ng,&nbsp;Wai Shan Wong","doi":"10.1002/jcla.25089","DOIUrl":"10.1002/jcla.25089","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alectinib is a second-generation anaplastic lymphoma kinase (ALK) inhibitor indicated for ALK-mutated non-small-cell lung cancer. Recently, the association between alectinib and red cell morphological abnormalities has been reported in a few case series. This retrospective observational study aims to determine the frequency of occurrence of acanthocytosis in patients taking alectinib and to evaluate the red cell indices, biochemical markers of haemolysis and eosin-5-maleimide (EMA) binding assay results in patients receiving alectinib.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients who were on alectinib and had a complete blood count test performed in Queen Elizabeth Hospital Haematology Laboratory between 1 May 2021 and 31 August 2021 were included in the study. Haematological investigations that had been performed before and after the commencement of alectinib were reviewed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fifty patients receiving alectinib were evaluated in this analysis. One hundred per cent of patients showed 3+ acanthocytes on the peripheral blood smears. Compared with the test results before starting alectinib, the post-alectinib blood tests showed a significantly lower haemoglobin concentration, red blood cell count and haematocrit; and a significantly higher mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration and red cell distribution width. All the tested patients showed a marked reduction in EMA mean channel fluorescence compared with normal control.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our cohort revealed that alectinib caused significant acanthocytosis in all patients. Alectinib was also associated with changes in red cell indices and biochemical markers of haemolysis, compatible with a spherocytic and anisopoikilocytic morphology with haemolysis. Patients on alectinib had reduced EMA binding.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"38 13-14","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcla.25089","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916862","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}

{"title":"Frequency of rs1051338 and rs116928232 Variants in Individuals from Northwest Mexico","authors":"Angélica Alejandra Hernández-Orozco,&nbsp;Lennon Melendez-Aranda,&nbsp;Sandra del Carmen Mendoza-Ruvalcaba,&nbsp;Francisco Javier Perea-Díaz,&nbsp;Jorge J. Cebolla,&nbsp;Pilar Giraldo,&nbsp;Aniel Jessica Leticia Brambila-Tapia,&nbsp;José Elías García-Ortíz","doi":"10.1002/jcla.25083","DOIUrl":"10.1002/jcla.25083","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p><i>LIPA</i>, situated on chromosome 10q23.2-q23.3, encodes the enzyme lysosomal acid lipase (LAL) (EC 3.1.1.13). Genetic alterations in <i>LIPA</i> lead to lysosomal acid lipase deficiency (LALD), an inborn error causing lipid metabolism anomalies and impairing cholesterol and triacylglyceride degradation. Over 40 <i>LIPA</i> variants have been documented, yet this study focuses on just two. The rs1051338 variant (NM_000235:c.46A&gt;C) affects the signal peptide in Exon 2, whereas rs116928232, located in Exon 8, alters the splice site (NM_000235:c.894G&gt;A), impacting lysosomal acid lipase activity. Considering the diverse clinical manifestations of LALD and the rising hepatic steatosis prevalence in Mexican population, mainly due to diet, these variants were investigated within this demographic to uncover potential contributing factors. This study aimed to reveal the frequency of rs1051338 and rs116928232 among healthy mestizo individuals in Northwest Mexico, marking a significant genetic exploration in this demographic.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Three hundred ten healthy mestizo individuals underwent PCR-RFLP analysis for both variants, and Sanger sequencing was performed for variant rs116928232. Bioinformatic analysis was also performed to predict protein changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Allele frequencies for rs1051338 (FA = 0.39, <i>p</i> value = 0.15) and rs116928232 (FA = 0.0016, <i>p</i> value = 0.49) aligned with reported data, while bioinformatic analysis allowed us to identify the protein alteration observed in both variants; finally, the variants showed no linkage between them (normalized <i>D</i>′ = 1.03, <i>p</i> value = 0.56).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Allelic frequencies closely matched reported data, and protein structure analysis confirmed variant impacts on LAL enzyme function. Notably, this study marks the first analysis of rs1051338 and rs116928232 in a healthy Mexican mestizo population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"38 13-14","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcla.25083","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893556","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}

{"title":"Importance of In Vitro Embryo Model Procedure Standardization","authors":"Kubilay Doğan Kılıç,&nbsp;Zeynep Simge Yılmaz","doi":"10.1002/jcla.25082","DOIUrl":"10.1002/jcla.25082","url":null,"abstract":"<p>In vivo studies offer a detailed understanding of organism functioning, surpassing the insights provided by in vitro studies. These experiments are crucial for comprehending disease emergence, progression, and associated mechanisms in humans, as well as for developing treatments. When choosing experimental models, factors such as genomic similarity, physiological relevance, ethical appropriateness, and economic feasibility must be considered. Standardized protocols enhance the reliability, and reproducibility of scientific methods, promoting the assessment of research in the scientific literature. Researchers conducting embryo studies should establish and document standardized protocols for increased data comparability. Standardization is vital for scientific validity, reproducibility, and comparability in both in vivo and in vitro studies, ensuring the accuracy and reliability of experimental results and advancing scientific knowledge.</p>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"38 13-14","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcla.25082","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788232","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}

{"title":"Unlocking Optimal Glycemic Interpretation: Redefining HbA1c Analysis in Female Patients With Diabetes and Iron-Deficiency Anemia Using Machine Learning Algorithms","authors":"Kadra Mohamed Abdillahi,&nbsp;Fatma Ceyla Eraldemir,&nbsp;Irfan Kösesoy","doi":"10.1002/jcla.25087","DOIUrl":"10.1002/jcla.25087","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>In response to the nuanced glycemic challenges faced by women with iron deficiency anemia (IDA) associated with diabetes, this study uses advanced machine learning algorithms to redefine hemoglobin (Hb)A1c measurement values. We aimed to improve the accuracy of glycemic interpretation by recognizing the critical interaction between erythrocytes, iron, and glycemic levels in this specific demographic group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective observational study included 17,526 adult women with HbA1c levels recorded from 2017 to 2022. Samples were classified as diabetic, prediabetic, or non-diabetic based on HbA1c and fasting blood glucose (FBG) levels for distribution analysis without impacting model training. Support Vector Machines, Linear Regression, Random Forest, and K-Nearest Neighbor algorithms as machine learning (ML) methods were used to predict HbA1c levels. Following the training of the model, HbA1c values were predicted for the IDA samples using the trained model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>According to our results, there has been a 0.1 unit change in HbA1c values, which has resulted in a clinical decision change in some patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Using ML to analyze HbA1c results in women with IDA may unveil distinctions among patients whose HbA1c values hover near critical medical decision thresholds. This intersection of technology and laboratory science holds promise for enhancing precision in medical decision-making processes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"38 13-14","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcla.25087","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563454","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}

{"title":"A Study on Associations of Long Noncoding RNA HOTAIR Polymorphisms With Genetic Susceptibility to Chronic Kidney Disease","authors":"Mahdi Majidpour,&nbsp;Ramin Saravani,&nbsp;Saman Sargazi,&nbsp;Sara Sargazi,&nbsp;Mahdiyeh Harati-Sadegh,&nbsp;Shadi Khorrami,&nbsp;Mohammad Sarhadi,&nbsp;Ali Alidadi","doi":"10.1002/jcla.25086","DOIUrl":"10.1002/jcla.25086","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The importance of long noncoding RNAs (lncRNAs) in various biological processes has been increasingly recognized in recent years. This study investigated how gene polymorphism in HOX transcript antisense RNA (HOTAIR) lncRNA affects the predisposition to chronic kidney disease (CKD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study comprised 150 patients with CKD and 150 healthy controls. A PCR-RFLP and ARMS-PCR techniques were used for genotyping the five target polymorphisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>According to our findings, rs4759314 confers strong protection against CKD in allelic, dominant, and codominant heterozygote genetic patterns. Furthermore, rs3816153 decreased CKD risk by 78% when TT versus GG, 55% when GG+GT versus TT, and 74% when GT versus TT+GG. In contrast, the CC+CT genotype [odds ratio (OR) = 1.66, 95% confidence intervals (CIs) = 1.05–2.63] and the T allele (OR = 1.50, 95% CI = 1.06–2.11) of rs12826786, as well as the TT genotype (OR = 2.52, 95% CI = 1.06–5.98) of rs3816153 markedly increased the risk of CKD in the Iranian population. Although no linkage disequilibrium was found between the studied variants, the C_rs12826786T_rs920778G_rs1899663G_rs4759314G_rs3816153 haplotype was associated with a decreased risk of CKD by 86% (OR = 0.14, 95% CI = 0.03–0.66).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The rs920778 was not correlated with CKD risk, whereas the <i>HOTAIR</i> rs4759314, rs12826786, rs1899663, and rs3816153 polymorphisms affected the risk of CKD in our population. It seems essential to conduct repeated studies across various ethnic groups to explore the link between <i>HOTAIR</i> variants and their impact on the disease outcome.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"38 11-12","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcla.25086","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492205","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}

{"title":"Importance of CD71+ Erythrocyte Cell Levels in Prognosis in Patients With β-Thalassemia","authors":"Gizem Zorlu Görgülügil,&nbsp;Ayşegül Uğur Kurtoğlu,&nbsp;Sevcan Uğur,&nbsp;Erdal Kurtoğlu","doi":"10.1002/jcla.25084","DOIUrl":"10.1002/jcla.25084","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background/Objectives</h3>\u0000 \u0000 <p>CD71⁺ erythroid cells (CECs) are immature red blood cells (proerythroblasts, erythroblasts, and reticulocytes). CECs play an important role in the development of sepsis and cancer by causing immunosuppression. We examined the CEC levels in the peripheral blood of beta thalassemia (βThal) patients and investigated the relationship between CECs and the clinical status of the patients, especially splenectomy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Sixty-eight patients with βThal (46 splenectomized and 22 nonsplenectomized) and 15 healthy controls were included in this study. The hemogram parameters, ferritin, and CECs (flow cytometry method) were measured.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>It was observed that the CEC level in the patient group was significantly higher than the control group (<i>p</i> &lt; 0.05). CEC levels were found to be significantly higher in patients with splenectomy than in patients with nonsplenectomy (<i>p</i> &lt; 0.05). CEC levels were higher in patients with nontransfusion-dependent βT (NTD-βThal) than in patients with transfusion-dependent βT (TD-βThal) (<i>p</i> &lt; 0.05). CEC levels were found to be significantly higher in patients with splenectomy than in patients with nonsplenectomy in both TD-βThal and NTD-βThal groups (<i>p</i> &lt; 0.05). There was a moderate-negative correlation was detected between CECs and Hb levels (<i>r</i> = −0.467; <i>p</i> &lt; 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>High CEC levels in βThal patients develop as a result of ineffective erythropoiesis. We think that keeping CEC levels under control is important for prognosis, especially in patients with splenectomy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"38 11-12","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcla.25084","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141457172","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}

{"title":"Identification of a Novel Deletion Variant (c.2999_3005delTGTGTGT/p.Asn1000SerfsTer4) in NPHP4 Associated With Nephronophthisis-4","authors":"Zahra Miri Karam,&nbsp;Atieh Karimi Gohari,&nbsp;Mohammad Javad Rezazadeh Khabaz,&nbsp;Abolfazl Yari,&nbsp;Seyed Mahdi Emami Meybodi,&nbsp;Rezvan Attari,&nbsp;Maryam Torabi,&nbsp;Farzane Vafaeie,&nbsp;Fateme Moradi Moraddahande,&nbsp;Sara Amiri,&nbsp;Kolsoum Saeidi","doi":"10.1002/jcla.25077","DOIUrl":"10.1002/jcla.25077","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Nephronophthisis-4 (NPHP4) is an inherited renal ciliopathy described by renal fibrosis and progressive impairment of kidney function. This study aimed to investigate the genetic basis and clinical manifestations of NPHP4 in two Iranian siblings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The proband was a 27-year-old male with features of end-stage renal disease, including anemia, uremia, polyuria, and polydipsia. It is worth mentioning that he has a 22-year-old sister with a similar presentation. Clinical diagnosis procedures, such as renal biopsy, brain imaging, blood and urine tests, cardiac evaluation, ophthalmic inspection, and auditory function assessment, were carried out to evaluate organ involvement and potential comorbidities. Whole-exome sequencing (WES) and segregation analysis were performed to identify and confirm genetic variants associated with the condition. Computational variant analysis was conducted to evaluate the pathogenicity of the candidate variant. Furthermore, the SWISS-MODEL server was utilized for protein modeling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The brain, cardiac, ocular, and auditory functions were normal. Renal biopsy of the proband showed chronic interstitial inflammation and fibrosis. We found a novel homozygous 7-base pair deletion (c.2999_3005delTGTGTGT/ p.Asn1000SerfsTer4) in exon 21 of <i>NPHP4</i> by WES. Segregation analysis confirmed homozygosity for the NPHP4 variant in affected individuals and heterozygous carrier status in parents, supporting autosomal recessive inheritance. 3D protein modeling indicated significant structural changes due to the variant.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study expands the genetic causes and phenotypic spectrum of nephronophthisis-4 and reveals the importance of genetic analysis in diagnosing and managing rare inherited kidney disorders, particularly those involving consanguinity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"38 11-12","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcla.25077","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419363","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}

{"title":"The Rising Tide of Antibiotic Resistance: A Study on Extended-Spectrum Beta-Lactamase and Carbapenem-Resistant Escherichia coli and Klebsiella pneumoniae","authors":"Hasan Ejaz,&nbsp;Muhammad Usman Qamar,&nbsp;Aisha Farhana,&nbsp;Sonia Younas,&nbsp;Alia Batool,&nbsp;Durreshahwar Lone,&nbsp;Muhammad Atif,&nbsp;Mashael W. Alruways,&nbsp;Muharib Alruwaili,&nbsp;Ismail Hamad,&nbsp;Samy Selim,&nbsp;Bi Bi Zainab Mazhari,&nbsp;Ali Farooq,&nbsp;Kashaf Junaid","doi":"10.1002/jcla.25081","DOIUrl":"10.1002/jcla.25081","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The global spread of extended-spectrum beta-lactamase (ESBL)-producing and carbapenem-resistant Enterobacterales (CRE) poses a significant concern. Acquisition of antimicrobial resistance genes leads to resistance against several antibiotics, limiting treatment options. We aimed to study ESBL-producing and CRE transmission in clinical settings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>From clinical samples, 227 ESBL-producing and CRE isolates were obtained. The isolates were cultured on bacterial media and confirmed by VITEK 2. Antibiograms were tested against several antibiotics using VITEK 2. The acquired resistance genes were identified by PCR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the 227 clinical isolates, 145 (63.8%) were <i>Klebsiella pneumoniae</i> and 82 (36.1%) were <i>Escherichia coli</i>; 76 (33.4%) isolates were detected in urine, 57 (25.1%) in pus swabs, and 53 (23.3%) in blood samples. A total of 58 (70.7%) ESBL-producing <i>E. coli</i> were resistant to beta-lactams, except for carbapenems, and 17.2% were amikacin-resistant; 29.2% of <i>E. coli</i> isolates were resistant to carbapenems. A total of 106 (73.1%) ESBL-producing <i>K. pneumoniae</i> were resistant to all beta-lactams, except for carbapenems, and 66.9% to ciprofloxacin; 38 (26.2%) <i>K. pneumoniae</i> were resistant to carbapenems. Colistin emerged as the most effective antibiotic against both bacterial types. Twelve (20.6%) <i>E. coli</i> isolates were positive for <i>bla</i>_CTX-M, 11 (18.9%) for <i>bla</i>_TEM, and 8 (33.3%) for <i>bla</i>_NDM. Forty-six (52.3%) <i>K. pneumoniae</i> isolates had <i>bla</i>_CTX-M, 27 (18.6%) <i>bla</i>_TEM, and 26 (68.4%) <i>bla</i>_NDM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study found a high prevalence of drug-resistant ESBL-producing and CRE, highlighting the need for targeted antibiotic use to combat resistance.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"38 10","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11211664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141331068","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}

{"title":"Novel Germline KIT Variants in Families With Severe Piebaldism: Case Series and Literature Review","authors":"Yuanyuan Zhang,&nbsp;Haiming Gao,&nbsp;Lu Zhang,&nbsp;Yunjing Zhao,&nbsp;Chuang Qiu,&nbsp;Xiaoliang Liu","doi":"10.1002/jcla.25073","DOIUrl":"10.1002/jcla.25073","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Piebaldism is a rare autosomal dominant disorder characterized by congenital white forelock and depigmented patches, which is most commonly caused by deleterious variants in the <i>KIT</i> gene.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Four <i>KIT</i> variants were identified in a piebaldism case series by whole-exome sequencing. Functional experiments, including in vitro minigene reporter assay and enzyme-linked immunosorbent assay, were carried out to elucidate the pathogenicity of the variants. The genotype–phenotype correlation was summarized through extensive literature reviewing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>All the four cases had severe piebaldism presented with typical white forelock and diffuse depigmentation on the ventral trunk and limbs. Four germline variants at the tyrosine kinase (TK) domains of the <i>KIT</i> gene were identified: two novel variants c.1990+1G&gt;A (p.Pro627_Gly664delinsArg) and c.2716T&gt;C (p.Cys906Arg), and two known variants c.1879+1G&gt;A (p.Gly592_Pro627delinsAla) and c.1747G&gt;A (p.Glu583Lys). Both splicing variants caused exon skipping and inframe deletions in the TK1 domain. The missense variants resided at the TK1 and TK2 domains respectively impairing PI3K/AKT and MAPK/ERK signaling pathways, the downstream of KIT. All severe cases were associated with variants in the TK domains, eliciting a major dominant-negative mechanism of the disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our data expand the mutation spectrum of <i>KIT</i>, emphasized by a dominant-negative effect of variants in the critical TK domains in severe cases. We also share the experience of prenatal diagnosis and informed reproductive choices for the affected families.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"38 11-12","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcla.25073","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419319","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}