Molecular Diagnosis & Therapy最新文献

{"title":"Long-Read Nanopore Sequencing of RPGR ORF15 is Enhanced Following DNase I Treatment of MinION Flow Cells.","authors":"Samar Yahya,&nbsp;Christopher M Watson,&nbsp;Ian Carr,&nbsp;Martin McKibbin,&nbsp;Laura A Crinnion,&nbsp;Morag Taylor,&nbsp;Hope Bonin,&nbsp;Tracy Fletcher,&nbsp;Mohammed E El-Asrag,&nbsp;Manir Ali,&nbsp;Carmel Toomes,&nbsp;Chris F Inglehearn","doi":"10.1007/s40291-023-00656-z","DOIUrl":"10.1007/s40291-023-00656-z","url":null,"abstract":"<p><strong>Introduction: </strong>RPGR ORF15 is an exon present almost exclusively in the retinal transcript of RPGR. It is purine-rich, repetitive and notoriously hard to sequence, but is a hotspot for mutations causing X-linked retinitis pigmentosa.</p><p><strong>Methods: </strong>Long-read nanopore sequencing on MinION and Flongle flow cells was used to sequence RPGR ORF15 in genomic DNA from patients with inherited retinal dystrophy. A flow cell wash kit was used on a MinION flow cell to increase yield. Findings were confirmed by PacBio SMRT long-read sequencing.</p><p><strong>Results: </strong>We showed that long-read nanopore sequencing successfully reads through a 2 kb PCR-amplified fragment containing ORF15. We generated reads of sufficient quality and cumulative read-depth to detect pathogenic RP-causing variants. However, we observed that this G-rich, repetitive DNA segment rapidly blocks the available pores, resulting in sequence yields less than 5% of the expected output. This limited the extent to which samples could be pooled, increasing cost. We tested the utility of a MinION wash kit containing DNase I to digest DNA fragments remaining on the flow cell, regenerating the pores. Use of the DNase I treatment allowed repeated re-loading, increasing the sequence reads obtained. Our customised workflow was used to screen pooled amplification products from previously unsolved inherited retinal disease (IRD) in patients, identifying two new cases with pathogenic ORF15 variants.</p><p><strong>Discussion: </strong>We report the novel finding that long-read nanopore sequencing can read through RPGR-ORF15, a DNA sequence not captured by short-read next-generation sequencing (NGS), but with a more reduced yield. Use of a flow cell wash kit containing DNase I unblocks the pores, allowing reloading of further library aliquots over a 72-h period, increasing yield. The workflow we describe provides a novel solution to the need for a rapid, robust, scalable, cost-effective ORF15 screening protocol.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/29/d6/40291_2023_Article_656.PMC10299921.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9707043","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":"Nucleic Acid Quality Assessment is Critical to the Success of the Oncomine Dx Target Test for Lung Cancer.","authors":"Yuki Nagakubo,&nbsp;Yosuke Hirotsu,&nbsp;Kenji Amemiya,&nbsp;Hitoshi Mochizuki,&nbsp;Toshiharu Tsutsui,&nbsp;Yumiko Kakizaki,&nbsp;Yoshihiro Miyashita,&nbsp;Rumi Higuchi,&nbsp;Takahiro Nakagomi,&nbsp;Taichiro Goto,&nbsp;Toshio Oyama,&nbsp;Masao Omata","doi":"10.1007/s40291-023-00653-2","DOIUrl":"10.1007/s40291-023-00653-2","url":null,"abstract":"<p><strong>Background and objective: </strong>The Oncomine Dx Target Test (ODxTT) has been used as a companion diagnostic test for lung cancer. Here, we evaluated whether the amount of nucleic acid and the degree of RNA degradation are related to the success of the ODxTT.</p><p><strong>Methods: </strong>This study included 223 samples from 218 patients with lung cancer. For all samples, DNA and RNA concentrations were quantified using Qubit, and the degree of RNA degradation was evaluated using the Bioanalyzer.</p><p><strong>Results: </strong>Of the 223 samples, 219 samples were successfully analyzed in the ODxTT and four were not. DNA analysis failed in two samples, which were attributed to low DNA concentrations and both were cytology specimens. Meanwhile, RNA analysis failed in the other two samples. These samples had sufficient amounts of RNA, but it was highly degraded with DV200 (the percentage of RNA fragments > 200 base pairs) less than 30. Compared with RNA samples with DV200 ≥ 30, analysis of RNA with DV200 < 30 yielded significantly fewer reads for the internal control genes. This test showed actionable mutations were identified in 38% (83/218) of all patients and in 46.6% (76/163) of patients with lung adenocarcinoma.</p><p><strong>Conclusions: </strong>DNA concentration and degree of RNA degradation are key factors determining the success of diagnostic testing by the ODxTT.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9751196","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":"Urothelial Bladder Cancer: Genomic Alterations in Fibroblast Growth Factor Receptor.","authors":"Maroun Bou Zerdan,&nbsp;Gennady Bratslavsky,&nbsp;Joseph Jacob,&nbsp;Jeffrey Ross,&nbsp;Richard Huang,&nbsp;Alina Basnet","doi":"10.1007/s40291-023-00647-0","DOIUrl":"10.1007/s40291-023-00647-0","url":null,"abstract":"<p><strong>Background and objective: </strong>Genomic alterations in fibroblast growth factor receptor (FGFR) genes have been linked to a reduced response to immune checkpoint inhibitors. Some of the immune microenvironment of urothelial bladder cancer (UBC) could be distorted because of the inhibition of interferon signaling pathways. We present a landscape of FGFR genomic alterations in distorted UBC to evaluate the immunogenomic mechanisms of resistance and response.</p><p><strong>Methods: </strong>There were 4035 UBCs that underwent hybrid, capture-based comprehensive genomic profiling. Tumor mutational burden was determined in up to 1.1 Mbp of sequenced DNA and microsatellite instability was determined in 114 loci. Programmed death ligand expression in tumor cells was assessed by immunohistochemistry (Dako 22C3).</p><p><strong>Results: </strong>The FGFR tyrosine kinases were altered in 894 (22%) UBCs. The highest frequency of alterations was in FGFR genomic alterations with FGFR3 at 17.4% followed by FGFR1 at 3.7% and FGFR2 at 1.1%. No FGFR4 genomic alterations were identified. The age and sex distribution were similar in all groups. Urothelial bladder cancers that featured FGFR3 genomic alterations were associated with lower driver genomic alterations/tumors. 14.7% of the FGFR3 genomic alterations were FGFR3 fusions. Other findings included a significantly higher frequency of ERBB2 amplification in FGFR1/2-altered UBCs compared with FGFR3-altered UBCs. Urothelial bladder cancers with FGFR3 genomic alterations also had the highest frequency of the activating mTOR pathway. FGFR3-altered UBCs also featured significantly higher frequencies of biomarkers associated with a lack of response to immune checkpoint inhibitors including a lower tumor mutational burden, lower programmed death-ligand 1 expression, and higher frequencies of genomic alterations in MDM2. Also linked to IO drug resistance, CDKN2A/B loss and MTAP loss were observed at a higher frequency in FGFR3-driven UBC.</p><p><strong>Conclusions: </strong>An increased frequency of genomic alterations is observed in UBC FGFR. These have been linked to immune checkpoint inhibitor resistance. Clinical trials are needed to evaluate UBC FGFR-based biomarkers prognostic of an immune checkpoint inhibitor response. Only then can we successfully incorporate novel therapeutic strategies into the evolving landscape of UBC treatment.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10053969","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":"Relationship between Proclarix and the Aggressiveness of Prostate Cancer.","authors":"Miriam Campistol,&nbsp;Marina Triquell,&nbsp;Lucas Regis,&nbsp;Ana Celma,&nbsp;Inés de Torres,&nbsp;María E Semidey,&nbsp;Richard Mast,&nbsp;Olga Mendez,&nbsp;Jacques Planas,&nbsp;Enrique Trilla,&nbsp;Juan Morote","doi":"10.1007/s40291-023-00649-y","DOIUrl":"10.1007/s40291-023-00649-y","url":null,"abstract":"<p><strong>Introduction: </strong>Proclarix is a CE-marked test that provides the risk of clinically significant prostate cancer (csPCa), ranging from 0% to 100%, based on the serum measurement of Thrombospondin-1, cathepsin D, prostate-specific antigen (PSA), and percentage of free PSA in addition to age. We hypothesize that Proclarix could be correlated with PCa aggressiveness. We analyzed the association of this new biomarker with four surrogates of aggressiveness: grade group (GG) in the biopsy, clinical stage, risk of biochemical recurrence after primary treatment of localized PCa, and pathology in the surgical specimen.</p><p><strong>Material and methods: </strong>This is a retrospective study from 606 men with suspicion of PCa [PSA of ≥ 3.0 ng/mL and/or abnormal digital rectal examination (DRE)], in whom Proclarix was assessed (0-100%). The GG was defined by the International Society of Urological Pathology categories. The TNM was used for clinical staging (cT based on DRE, whereas cN and cM were established with computed tomography and 99-technetium bone scintigraphy). The risk of biochemical recurrence of localized PCa after primary treatment was defined by combining PSA, GG, and cT. Finally, an unfavorable pathology in a surgical specimen was defined as GG > 2 or pT ≥ 3.</p><p><strong>Results: </strong>The median age of the cohort was 67 years old, with a median PSA of 7 ng/mL and a rate of abnormal DRE of 23.3%. CsPCa was detected in 254 men (41.9%), with a median Proclarix of 60.1% compared with 37.3% obtained in patients with insignificant PCa and 20.7% in men without PCa. Among patients with GG > 3, Proclarix was significantly higher (58.2%) than in those with GG of 3 or lower (33.1%, p < 0.001). Men with localized tumors exhibited a Proclarix median of 37.3% compared with those with advanced disease (60.1%, p < 0.001). Proclarix levels among 197 patients with low and intermediate risk of biochemical recurrence were 24.9% and 35.0%, respectively, significantly lower compared with patients with high-risk disease (58.7%, p < 0.001). Unfavorable pathology was observed in 35 patients out of the 79 who underwent radical prostatectomy, with a Proclarix median of 35.7% compared with 23.7% obtained in patients with favorable pathology (p = 0.013). Proclarix and magnetic resonance imaging were independent predictors of the four surrogates of aggressiveness analyzed.</p><p><strong>Conclusion: </strong>There is a correlation between Proclarix and the aggressiveness of PCa.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10073238","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":"Recent Advancements in Nanomaterials: A Promising Way to Manage Neurodegenerative Disorders.","authors":"Thuy Trang Nguyen,&nbsp;Phuong-Trang Nguyen-Thi,&nbsp;Thi Hong Anh Nguyen,&nbsp;Thanh-Tam Ho,&nbsp;Nguyen-Minh-An Tran,&nbsp;Toi Van Vo,&nbsp;Giau Van Vo","doi":"10.1007/s40291-023-00654-1","DOIUrl":"10.1007/s40291-023-00654-1","url":null,"abstract":"<p><p>Neurodegenerative diseases (NDs) such as dementia, Alzheimer's disease, Parkinson's disease, frontotemporal dementia, and amyotrophic lateral sclerosis are some of the most prevalent disorders currently afflicting healthcare systems. Many of these diseases share similar pathological hallmarks, including elevated oxidative stress, mitochondrial dysfunction, protein misfolding, excitotoxicity, and neuroinflammation, all of which contribute to the deterioration of the nervous system's structure and function. The development of diagnostic and therapeutic materials in the monitoring and treatment of these diseases remains challenging. One of the biggest challenges facing therapeutic and diagnostic materials is the blood-brain barrier (BBB). The BBB is a multifunctional membrane possessing a plethora of biochemical, cellular, and immunological features that ensure brain homeostasis by preventing the entry and accumulation of unwanted compounds. With regards to neurodegenerative diseases, the recent application of tailored nanomaterials (nanocarriers and nanoparticles) has led to advances in diagnostics and therapeutics. In this review, we provide an overview of commonly used nanoparticles and their applications in NDs, which may offer new therapeutic strategies for the prevention and treatment of neurodegenerative diseases.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10073269","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":"Validation of a Transcriptome-Based Assay for Classifying Cancers of Unknown Primary Origin.","authors":"Jackson Michuda,&nbsp;Alessandra Breschi,&nbsp;Joshuah Kapilivsky,&nbsp;Kabir Manghnani,&nbsp;Calvin McCarter,&nbsp;Adam J Hockenberry,&nbsp;Brittany Mineo,&nbsp;Catherine Igartua,&nbsp;Joel T Dudley,&nbsp;Martin C Stumpe,&nbsp;Nike Beaubier,&nbsp;Maryam Shirazi,&nbsp;Ryan Jones,&nbsp;Elizabeth Morency,&nbsp;Kim Blackwell,&nbsp;Justin Guinney,&nbsp;Kyle A Beauchamp,&nbsp;Timothy Taxter","doi":"10.1007/s40291-023-00650-5","DOIUrl":"10.1007/s40291-023-00650-5","url":null,"abstract":"<p><strong>Introduction: </strong>Cancers assume a variety of distinct histologies, and may originate from a myriad of sites including solid organs, hematopoietic cells, and connective tissue. Clinical decision-making based on consensus guidelines such as the National Comprehensive Cancer Network (NCCN) is often predicated on a specific histologic and anatomic diagnosis, supported by clinical features and pathologist interpretation of morphology and immunohistochemical (IHC) staining patterns. However, in patients with nonspecific morphologic and IHC findings-in addition to ambiguous clinical presentations such as recurrence versus new primary-a definitive diagnosis may not be possible, resulting in the patient being categorized as having a cancer of unknown primary (CUP). Therapeutic options and clinical outcomes are poor for patients with CUP, with a median survival of 8-11 months.</p><p><strong>Methods: </strong>Here, we describe and validate the Tempus Tumor Origin (Tempus TO) assay, an RNA-sequencing-based machine learning classifier capable of discriminating between 68 clinically relevant cancer subtypes. Model accuracy was assessed using primary and/or metastatic samples with known subtype.</p><p><strong>Results: </strong>We show that the Tempus TO model is 91% accurate when assessed on both a retrospectively held out cohort and a set of samples sequenced after model freeze that collectively contained 9210 total samples with known diagnoses. When evaluated on a cohort of CUPs, the model recapitulated established associations between genomic alterations and cancer subtype.</p><p><strong>Discussion: </strong>Combining diagnostic prediction tests (e.g., Tempus TO) with sequencing-based variant reporting (e.g., Tempus xT) may expand therapeutic options for patients with cancers of unknown primary or uncertain histology.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/49/44/40291_2023_Article_650.PMC10300170.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9706378","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":"Dynamic ctDNA Mutational Complexity in Patients with Melanoma Receiving Immunotherapy.","authors":"Sandra Fitzgerald, Cherie Blenkiron, Rosalie Stephens, Jon A Mathy, Tiffany Somers-Edgar, Gill Rolfe, Richard Martin, Christopher Jackson, Michael Eccles, Tamsin Robb, Euan Rodger, Ben Lawrence, Parry Guilford, Annette Lasham, Cristin G Print","doi":"10.1007/s40291-023-00651-4","DOIUrl":"10.1007/s40291-023-00651-4","url":null,"abstract":"<p><strong>Background: </strong>Circulating tumour DNA (ctDNA) analysis promises to improve the clinical care of people with cancer, address health inequities and guide translational research. This observational cohort study used ctDNA to follow 29 patients with advanced-stage cutaneous melanoma through multiple cycles of immunotherapy.</p><p><strong>Method: </strong>A melanoma-specific ctDNA next-generation sequencing (NGS) panel, droplet digital polymerase chain reaction (ddPCR) and mass spectrometry analysis were used to identify ctDNA mutations in longitudinal blood plasma samples from Aotearoa New Zealand (NZ) patients receiving immunotherapy for melanoma. These technologies were used in conjunction to identify the breadth and complexity of tumour genomic information that ctDNA analysis can reliably report.</p><p><strong>Results: </strong>During the course of immunotherapy treatment, a high level of dynamic mutational complexity was identified in blood plasma, including multiple BRAF mutations in the same patient, clinically relevant BRAF mutations emerging through therapy and co-occurring sub-clonal BRAF and NRAS mutations. The technical validity of this ctDNA analysis was supported by high sample analysis-reanalysis concordance, as well as concordance between different ctDNA measurement technologies. In addition, we observed > 90% concordance in the detection of ctDNA when using cell-stabilising collection tubes followed by 7-day delayed processing, compared with standard EDTA blood collection protocols with rapid processing. We also found that the undetectability of ctDNA at a proportion of treatment cycles was associated with durable clinical benefit (DCB).</p><p><strong>Conclusion: </strong>We found that multiple ctDNA processing and analysis methods consistently identified complex longitudinal patterns of clinically relevant mutations, adding support for expanded clinical trials of this technology in a variety of oncology settings.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b2/3e/40291_2023_Article_651.PMC10131510.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9695320","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":"Smelling the Disease: Diagnostic Potential of Breath Analysis.","authors":"Anju Sharma, Rajnish Kumar, Pritish Varadwaj","doi":"10.1007/s40291-023-00640-7","DOIUrl":"10.1007/s40291-023-00640-7","url":null,"abstract":"<p><p>Breath analysis is a relatively recent field of research with much promise in scientific and clinical studies. Breath contains endogenously produced volatile organic components (VOCs) resulting from metabolites of ingested precursors, gut and air-passage bacteria, environmental contacts, etc. Numerous recent studies have suggested changes in breath composition during the course of many diseases, and breath analysis may lead to the diagnosis of such diseases. Therefore, it is important to identify the disease-specific variations in the concentration of breath to diagnose the diseases. In this review, we explore methods that are used to detect VOCs in laboratory settings, VOC constituents in exhaled air and other body fluids (e.g., sweat, saliva, skin, urine, blood, fecal matter, vaginal secretions, etc.), VOC identification in various diseases, and recently developed electronic (E)-nose-based sensors to detect VOCs. Identifying such VOCs and applying them as disease-specific biomarkers to obtain accurate, reproducible, and fast disease diagnosis could serve as an alternative to traditional invasive diagnosis methods. However, the success of VOC-based identification of diseases is limited to laboratory settings. Large-scale clinical data are warranted for establishing the robustness of disease diagnosis. Also, to identify specific VOCs associated with illness states, extensive clinical trials must be performed using both analytical instruments and electronic noses equipped with stable and precise sensors.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9893210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9419952","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":"A Cost-Effectiveness Analysis of Biomarkers for Risk Prediction in Atrial Fibrillation.","authors":"Gisèle Nakhlé, Jean-Claude Tardif, Denis Roy, Léna Rivard, Michelle Samuel, Anick Dubois, Jacques LeLorier","doi":"10.1007/s40291-023-00639-0","DOIUrl":"10.1007/s40291-023-00639-0","url":null,"abstract":"<p><strong>Rationale: </strong>Atrial fibrillation (AF) is associated with an increased risk of thromboembolism. This risk is currently assessed with scoring systems based on clinical characteristics. However, these tools have limited prognostic performance. Circulating biomarkers are proposed for improved prediction of major clinical events and individualization of treatments in patients with AF.</p><p><strong>Objective: </strong>The aim was to assess the cost-effectiveness of precision medicine (PM), i.e., the use of combined biomarkers and clinical variables, in comparison to standard of care (SOC) for risk stratification in a hypothetical cohort of AF patients at risk of stroke.</p><p><strong>Methods: </strong>A Markov cohort model was developed to evaluate the costs and quality-adjusted life-years (QALYs) of PM compared to SOC, over 20 years using a Canadian healthcare system perspective.</p><p><strong>Results: </strong>PM decreased the mean per-patient overall costs by 7% ($94,932 vs $102,057 [Canadian dollars], respectively) and increased the QALYs by 12% (8.77 vs 7.68 QALYs, respectively). The calculated incremental cost-effectiveness ratio was negative, indicating that PM is an economically dominant strategy. These results were robust to one-way and probabilistic sensitivity analyses.</p><p><strong>Conclusion: </strong>PM compared to SOC is economically dominant and is projected to generate cost savings.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/34/fa/40291_2023_Article_639.PMC9888735.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9779759","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":"Expression Signature of Immune-Related MicroRNAs in Autoimmune Skin Disease: Psoriasis and Vitiligo Insights.","authors":"Hoda Y Abdallah, Salwa Faisal, Noha Z Tawfik, Nourhan Hassan Soliman, Rania M Kishk, Alia Ellawindy","doi":"10.1007/s40291-023-00646-1","DOIUrl":"10.1007/s40291-023-00646-1","url":null,"abstract":"<p><strong>Background: </strong>Psoriasis and vitiligo are both chronic, skin-specific diseases classified as autoimmune diseases due to the involvement of several biochemical pathways in their pathogenesis, similar to those altered in other autoimmune diseases. The role of miRNAs in regulating skin autoimmune function has yet to be fully characterized.</p><p><strong>Aim: </strong>The aim of this study was to assess the expression profile of a panel of 11 circulating immune-related miRNAs in patients with autoimmune skin diseases, specifically psoriasis and vitiligo, and correlate their expression signature with the clinicopathological features of the diseases.</p><p><strong>Subjects and methods: </strong>Relative gene expression quantification for 11 immune-related circulating miRNAs in plasma was done for 300 subjects-100 patients with psoriasis, 100 patients with vitiligo and 100 normal healthy volunteers-followed by different modalities of bioinformatics analysis for the results.</p><p><strong>Results: </strong>The expression levels of all the studied immune-related miRNAs were elevated in both autoimmune skin disorders, with much higher levels of expression in psoriasis than in vitiligo patients. There was a significant correlation between most of the studied miRNAs, suggesting shared target genes and/or pathways. Moreover, all the studied miRNAs showed significant results as biomarkers for autoimmune skin disease, with miRNA-145 being the best candidate. Regarding the clinicopathological data, miRNA-7, miRNA-9, miRNA-145, miRNA-148a, and miRNA-148b were positively correlated with age. All the miRNAs were inversely correlated with obesity and disease duration.</p><p><strong>Conclusion: </strong>This study highlights the critical role of miRNAs in skin-specific autoimmune diseases that proved to be potential biomarkers for autoimmune skin disorders, warranting their exploration as therapeutic targets.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1f/71/40291_2023_Article_646.PMC10151313.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9483117","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}