Molecular Diagnosis & Therapy最新文献

{"title":"Advances and Challenges in the Diagnosis of Leishmaniasis.","authors":"Sanjana Mehrotra, Rahul Tiwari, Rajiv Kumar, Shyam Sundar","doi":"10.1007/s40291-024-00762-6","DOIUrl":"10.1007/s40291-024-00762-6","url":null,"abstract":"<p><p>Leishmaniasis remains a significant public health challenge, particularly in endemic regions with limited resources. Traditional diagnostic methods, including microscopy, culture, and serology, though widely utilized, often suffer from limitations such as variable  sensitivity, time delays, and the need for specialized infrastructure. Some of these limitations have been addressed with the emergence of molecular diagnostic techniques. Quantitative PCR (q-PCR), loop-mediated isothermal amplification (LAMP), and recombinase polymerase amplification (RPA) assays have improved  the diagnostic sensitivity and specificity, enabling species identification and detection of asymptomatic infections. Further, nanodiagnostics and portable sequencing technologies such as the MinION™, along with lab-on-chip platforms, are revolutionizing the diagnostic landscape of leishmaniasis by offering point-of-care (POC) options for remote settings and field-based diagnosis. This review provides an in-depth analysis of these cutting-edge advances, discusses their application in resource-constrained settings, and evaluates their potential to reshape the future of leishmaniasis diagnosis and management.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"195-212"},"PeriodicalIF":4.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Evidence of the Prevalence of Driver Mutations in Anorectal Melanoma.","authors":"E Jutten, L C L T van Kempen, G F H Diercks, B L van Leeuwen, S Kruijff, K P Wevers","doi":"10.1007/s40291-024-00764-4","DOIUrl":"10.1007/s40291-024-00764-4","url":null,"abstract":"<p><strong>Introduction: </strong>Anorectal melanoma is a rare neoplasm with an aggressive behavior and poor prognosis. Recently, recurrent gene mutations related to anorectal melanoma have been identified in a small series of cases, and this holds promise for targeted therapies, analogous to cutaneous melanoma. The purpose of this study was to analyze testing rates and prevalence of mutations in anorectal melanoma in the Dutch population.</p><p><strong>Methods: </strong>The Netherlands Cancer Registry and the Dutch Nationwide Pathology Databank were queried for all patients with a diagnosis of anorectal melanoma (2009-2019) and for whom a molecular analysis was performed. The genes that were tested and mutations that were reported were recorded. Mutation status was correlated with clinical characteristics.</p><p><strong>Results: </strong>In the period 2009-2019, 121 patients were diagnosed with anorectal melanoma. A molecular analysis was performed for 81 (67%) using single gene testing and various next-generation sequencing panels. Testing rates increased from 53% in 2009-2012 to 73% in 2016-2019. In 29/81 (36%) analyzed tumors, one or more mutations were reported: mutations in KIT (16/70, 23%), CTNNB1 (3/20, 15%), NRAS (6/60, 10%), BRAF non-V600E (4/74, 5%), GNAS (1/19, 5%), KRAS (1/28, 4%), BRAF V600E (1/74, 1%), and SF3B1 (1/1). In this cohort, a positive correlation was found between BRAF mutation status and age. Mutation status did not correlate with sex, date of diagnosis, tumor stage or surgical treatment. Survival was not influenced by any mutation status.</p><p><strong>Conclusion: </strong>KIT was the most frequently mutated gene in the 81 analyzed anorectal melanomas in the period 2009-2019. With the increasing testing rates and use of next generation sequencing, the molecular landscape of anorectal melanomas is gradually being revealed. Adoption of broad mutation analysis will reveal potentially actionable targets for treatment of patients with anorectal melanoma.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"229-238"},"PeriodicalIF":4.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing Rabies Diagnosis: Time for a New \"Gold Standard\"?","authors":"Lonika Lodha, Ashwini Manoor Ananda, Reeta S Mani","doi":"10.1007/s40291-024-00758-2","DOIUrl":"10.1007/s40291-024-00758-2","url":null,"abstract":"<p><p>Rabies, a neglected zoonosis, claims approximately 60,000 lives globally each year. One of the significant challenges in rabies control efforts is the lack of surveillance data and underreporting, stemming from inadequate diagnostic facilities, particularly in low- and middle-income countries. At present, the World Health Organization recognizes the fluorescent antibody test (FAT) on postmortem brain specimens as the \"gold standard\" for confirming rabies in humans and animals. In this opinion article, we highlight several limitations of FAT and advocate for superior alternatives to replace it as the reference diagnostic technique for rabies. We argue that molecular techniques, specifically PCR-based methods, offer rapid, accurate, and convenient means of laboratory confirmation for rabies. Their implementation is now feasible due to the expanded technical and logistical capabilities achieved during the COVID-19 pandemic.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"153-159"},"PeriodicalIF":4.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142669736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author's Reply to ''Comment on 'Prognostic and Clinical Significance of Human Leukocyte Antigen Class I Expression in Breast Cancer: A Meta-Analysis''.","authors":"Weiqiang Qiao, Zhiqiang Jia, Wanying Guo, Qipeng Liu, Xiao Guo, Miao Deng","doi":"10.1007/s40291-024-00765-3","DOIUrl":"10.1007/s40291-024-00765-3","url":null,"abstract":"","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"273-276"},"PeriodicalIF":4.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of [¹⁸F]F-FDG PET/CT for Predicting Histology and Prognosis in Patients with Thymic Lesions.","authors":"Daniele Antonio Pizzuto, Angelo Castello, Marco Chiappetta, Massimo Castellani, Salvatore Annunziata, Annalisa Campanella, Giuseppe Calabrese, Margherita Cattaneo, Lorenzo Rosso, Giacomo Cusumano, Filippo Lococo, Paolo Mendogni","doi":"10.1007/s40291-024-00767-1","DOIUrl":"10.1007/s40291-024-00767-1","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate whether 18F-fluorodeoxyglucose positron emission tomography-computed tomography ([¹⁸F]F-FDG PET/CT) metabolic parameters were associated with histology and to assess their prognostic role in patients with thymic lesions.</p><p><strong>Patients and methods: </strong>In total, 116 patients (49/67 M/F; mean age 59.5 years) who underwent preoperative [¹⁸F]F-FDG PET/CT and thymectomy from 2012 to 2022 were retrospectively analyzed. Associations between histology and metabolic parameters (maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), peak standardized uptake value (SUVpeak), total lesion glycolysis (TLG), metabolic tumor volume (MTV), ratio between target lesion and liver SUVmax (rPET), quotient of SUVpeak in the tumor residual and SUVmean in a 20-cm³ volume of interest (qPET), and tumor-to-mediastinum (T/M) were analyzed. Freedom from recurrence (FFR) was determined and compared using the Kaplan-Meier and the log-rank test. The median follow-up was 38 months (range 14-72 months).</p><p><strong>Results: </strong>In total, 27 thymic hyperplasia, 41 low-risk thymomas (LRT) (types A, AB, and B1), and 48 high-risk thymomas (HRT) (B2, B3 thymoma, and carcinoma) were included. SUVmax, SUVmean, SUVpeak, rPET, qPET, and T/M were significantly higher in HRT than LRT and hyperplasia (p < 0.001). TLG and MTV were significantly higher in patients with LRT (p < 0.001). Only rPET, qPET, and T/M remained significantly higher in HRT than in LRT subgroups (p = 0.042, p = 0.049, and p = 0.028, respectively). SUVmax, SUVmean, and SUVpeak cutoffs of < 4.3, < 2.87, and 4.03, respectively, significantly distinguished patients with longer FFR (p = 0.009, p = 0.05, and p = 0.05).</p><p><strong>Conclusions: </strong>Positron emission tomography (PET) metabolic parameters could help to differentiate thymic histotypes. Standardized uptake value (SUV)-based parameters appear promising to predict recurrent disease.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"239-248"},"PeriodicalIF":4.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inner Ear Gene Therapy: An Overview from Bench to Bedside.","authors":"Anselm Joseph Gadenstaetter, Paul Emmerich Krumpoeck, Lukas David Landegger","doi":"10.1007/s40291-024-00759-1","DOIUrl":"10.1007/s40291-024-00759-1","url":null,"abstract":"<p><p>Hearing loss represents a highly prevalent and debilitating sensory disorder affecting roughly one in five people worldwide. In a majority of patients with congenital hearing loss, genetic mutations cause the disease. Up until recently, therapeutic options for individuals with hearing loss were limited to hearing aids and different types of auditory implants. However, after numerous years of intensive basic and translational research, gene therapy strategies are now being investigated in clinical trials. First results show significant hearing improvement in treated patients, highlighting gene therapy's role as a promising treatment for certain forms of genetic hearing loss. In this article, we provide an overview of genetic hearing loss and inner ear gene therapy research including relevant strategies that have been established in animal models and will likely be investigated in human patients soon. Furthermore, we summarize and contextualize the novel findings of recently completed and ongoing clinical trials, and discuss future hurdles needed to be overcome to allow for a broad and safe clinical application of inner ear gene therapy.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"161-181"},"PeriodicalIF":4.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11861411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leveraging Multi-omics to Disentangle the Complexity of Ovarian Cancer.","authors":"Shijuan Lin, Lily L Nguyen, Alexandra McMellen, Michael S Leibowitz, Natalie Davidson, Daniel Spinosa, Benjamin G Bitler","doi":"10.1007/s40291-024-00757-3","DOIUrl":"10.1007/s40291-024-00757-3","url":null,"abstract":"<p><p>To better understand ovarian cancer lethality and treatment resistance, sophisticated computational approaches are required that address the complexity of the tumor microenvironment, genomic heterogeneity, and tumor evolution. The ovarian cancer tumor ecosystem consists of multiple tumors and cell types that support disease growth and progression. Over the last two decades, there has been a revolution in -omic methodologies to broadly define components and essential processes within the tumor microenvironment, including transcriptomics, metabolomics, proteomics, genome sequencing, and single-cell analyses. While most of these technologies comprehensively characterize a single biological process, there is a need to understand the biological and clinical impact of integrating multiple -omics platforms. Overall, multi-omics is an intriguing analytic framework that can better approximate biological complexity; however, data aggregation and integration pipelines are not yet sufficient to reliably glean insights that affect clinical outcomes.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"145-151"},"PeriodicalIF":4.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142669737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Somatic Genetic Variants in Superficial Vascular Malformations by Liquid Biopsy in a Cohort of 88 Patients from a French Hospital.","authors":"Franck Neil El Sissy, Annouk Bisdorff, Alexandre Perrier, Erell Guillerm, Jérôme Denis, Löetitia Favre, Mathilde Aubertin, Mélanie Eyries, Florence Coulet","doi":"10.1007/s40291-025-00770-0","DOIUrl":"https://doi.org/10.1007/s40291-025-00770-0","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objective: &lt;/strong&gt;Superficial vascular anomalies are complex disorders characterized by abnormal vascular growth. Next-generation sequencing has recently identified somatic genetic alterations associated with these malformations, offering new insights for targeted treatments. However, tissue biopsies for genetic testing can be invasive and difficult to obtain, especially in arteriovenous malformations (AVM) with hemorrhagic risks. A liquid biopsy, a non-invasive approach, offers a promising solution by detecting genetic mutations in cell-free DNA. This pilot study aimed to evaluate the feasibility of using a liquid biopsy for the genetic analysis of patients with superficial vascular anomalies through cell-free DNA sampling. Additionally, it explored whether specific sampling sites, such as the afferent artery, nidus, and efferent vein, could enhance the sensitivity of detecting pathogenic variants in patients with AVM.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A total of 88 patients were enrolled, including 55 with AVM and 33 with lymphatic malformations. For patients with AVM, cell-free DNA samples were collected from peripheral blood, efferent veins, afferent arteries, and the AVM nidus. In patients with lymphatic malformations, cystic lymphatic fluid was collected by a direct puncture during diagnostic procedures. A molecular analysis was performed using a targeted gene panel relevant to somatic alterations in solid tumors. Pathogenic variants were validated by digital polymerase chain reaction for patients with lymphatic malformations.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Pathogenic variants were identified in 23.6% of patients with AVM, predominantly in MAP2K1 and KRAS genes, with higher sensitivity near the AVM nidus. In addition, pathogenic variants were identified in 27.3% of patients with lymphatic malformations, all involving the PIK3CA gene. Despite the lower sensitivity of a cell-free DNA analysis compared with a tissue biopsy, especially in patients with AVM, the detection rate suggests the utility for a cell-free DNA analysis, particularly when a tissue biopsy is not feasible.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This study confirms the feasibility of using a cell-free DNA liquid biopsy for genotyping patients with superficial vascular anomalies, although a tissue biopsy remains the gold standard for comprehensive genetic profiling because of its higher sensitivity. A liquid biopsy offers a non-invasive option for molecular analysis that is useful as a preliminary or alternative approach when direct tissue sampling is not possible. Importantly, the sensitivity of cell-free DNA sampling in AVM appeared highest when obtained close to the nidus, indicating an optimal sampling location for future studies. Further research is needed to improve detection sensitivity, especially for samples taken near the nidus, to validate and strengthen these findings. Although our study focused on superficial/extra-cranial AVM, further rese","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Obecabtagene Autoleucel: First Approval.","authors":"Arnold Lee","doi":"10.1007/s40291-025-00771-z","DOIUrl":"https://doi.org/10.1007/s40291-025-00771-z","url":null,"abstract":"<p><p>Obecabtagene autoleucel (AUCATZYL^®) is a CD19-directed genetically modified autologous T cell immunotherapy which is being developed by Autolus for the treatment of hematological cancers and systemic lupus erythematosus. In comparison with other chimeric antigen receptor T (CAR T) therapies, obecabtagene autoleucel has a fast off-rate binder for CD19. Obecabtagene autoleucel received approval following positive results from the FELIX phase I/II trial in adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL), and it is the first CAR T therapy that does not have mandatory Risk Evaluation Mitigation Strategy monitoring requirements. This article summarizes the milestones in the development of obecabtagene autoleucel leading to this first approval for the treatment of adults with relapsed or refractory B-cell precursor ALL.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Therapeutics in Development to Treat Hyperlipoproteinemia.","authors":"Maud Ahmad, Robert A Hegele","doi":"10.1007/s40291-024-00768-0","DOIUrl":"https://doi.org/10.1007/s40291-024-00768-0","url":null,"abstract":"<p><p>Clinical endpoints caused by hyperlipoproteinemia include atherosclerotic cardiovascular disease and acute pancreatitis. Emerging lipid-lowering therapies targeting proprotein convertase subtilisin/kexin 9 (PCSK9), lipoprotein(a), apolipoprotein C-III, and angiopoietin-like protein 3 represent promising advances in the management of patients with hyperlipoproteinemia. These therapies offer novel approaches for lowering pathogenic lipid and lipoprotein species, particularly in patients with serious perturbations who are not adequately controlled with conventional treatments or who are unable to tolerate them. Molecular targets for these novel therapeutic agents were identified and validated through genetic epidemiology studies. Proprotein convertase subtilisin/kexin 9 inhibitors (e.g., monoclonal antibodies and small interfering RNA) have revolutionized hypercholesterolemia management by significantly reducing both low-density lipoprotein cholesterol levels and major cardiovascular events. Genome editing of PCSK9 promises to provide a potential cure for patients with familial hypercholesterolemia. Several investigational lipoprotein(a)-targeting therapies aim to reduce the risk of atherosclerotic cardiovascular disease and aortic valve disease, although definitive clinical endpoint studies remain to be completed. Inhibition of APOC3 messenger RNA expression by olezarsen and plozasiran significantly lowers plasma triglyceride levels and markedly reduces pancreatitis risk in patients with familial chylomicronemia syndrome. Finally, angiopoietin-like protein 3 inhibition by the monoclonal antibody evinacumab has transformed management of patients with homozygous familial hypercholesterolemia. Together, these novel agents expand the therapeutic cache, offering personalized lipid-lowering strategies for high-risk patients with hyperlipoproteinemia, improving clinical outcomes and addressing previously unmet medical needs.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}