Clinical and translational discovery最新文献

{"title":"Towards a one-time cure for Fabry disease: Lentivirus-mediated haematopoietic stem and progenitor cell gene therapy","authors":"Rina Kansal","doi":"10.1002/ctd2.70042","DOIUrl":"https://doi.org/10.1002/ctd2.70042","url":null,"abstract":"<p>Fabry disease, also known as Anderson‒Fabry disease, is an X-linked systemic disease first described independently in Germany and England over 125 years ago, in 1898, in patients presenting with small, reddish purple telangiectatic cutaneous papules called <i>angiokeratoma corporis diffusum</i>.<span><sup>1</sup></span> Five decades later, in 1947, the concept of a lipid storage disease emerged following postmortem studies, and the abnormal lipid was identified as trihexosyl ceramide in 1963.<span><sup>1</sup></span> Subsequently, the underlying deficiency of the lysosomal enzyme α-galactosidase, which cleaves galactose from the neutral glycosphingolipid, globotriaosylceramide (Gb<sub>3</sub>) or trihexosyl ceramide, in the normal cellular degradation pathway, was identified.<span><sup>1, 2</sup></span> The enzyme activity was near-completely deficient in leukocytes in affected males and reduced in female carriers of the disease compared to normal leukocytes.<span><sup>2</sup></span> In 1978, the α-galactosidase A (<i>GLA)</i> gene, which encodes the enzyme, was found to be located in the Xq22 chromosomal region, and the gene's nucleotide sequence was identified in 1986. Gene mutations in <i>GLA</i> that do not allow enzyme expression were recognised as the fundamental cause of Fabry disease.<span><sup>3</sup></span></p><p>Although the clinical features of this inherited disease, including neurologic pain in the extremities, cutaneous angiokeratomas, hypohidrosis, and corneal opacities, are evident in childhood, the diagnosis of classic Fabry disease is often missed and delayed, with an average age of 29 years at diagnosis.<span><sup>3, 4</sup></span> The disease worsens in untreated adults due to the progressive accumulation of glycosphingolipids in various cells across multiple organ systems, leading to cardiovascular, cerebrovascular, and renal damage that shortens lifespan. Females exhibit variability in disease severity and may be asymptomatic or experience complications like affected males. Until 2001, no treatment was available to halt disease progression, when enzyme replacement therapy (ERT) was approved for treating Fabry disease in Europe, followed by approval in the United States in 2003.<span><sup>4</sup></span> Nonetheless, ERT is very expensive, requires biweekly infusions for life, and its efficacy may be reduced if the patient develops an antibody response. Migalastat, a pharmacologic chaperone therapy approved for adults with Fabry disease since 2016, is only applicable for 30%–50% of patients who have <i>GLA</i> mutations that are amenable to increase the activity of the deficient enzyme with the drug; furthermore, the in vitro determinations of amenability do not translate to in vivo drug efficacy.<span><sup>5</sup></span></p><p>Medin et al. began their gene therapy efforts more than two decades ago with the vision of developing a one-time cure for Fabry disease.<span><sup>6, 7</sup></span> In an accompanying article in thi","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"5 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell therapy based on stem cells or their extracellular vesicles during kidney graft preservation: Current state of the art and novelties","authors":"Nessma Chenaf-Benabdelmoumene, Thierry Hauet, Clara Steichen","doi":"10.1002/ctd2.70040","DOIUrl":"https://doi.org/10.1002/ctd2.70040","url":null,"abstract":"<p>Transplantation often remains the best therapeutic option in terms of life quality and disease prognosis improvement to treat chronic or even acute organ failure. According to a report published by the World Health Organization in 2023,<span><sup>1</sup></span> less than 10% of the world's organ needs are covered. Focusing on the kidney, which is now the most transplanted organ in the world, the latest report of the Global Observatory on Donation and Transplantation published in 2023 (based on 2022 data)<span><sup>2</sup></span> pointed out the gap between supply and demand: there are currently more patients on the active waiting list than there are grafts available for them worldwide. Kidney grafts can come from two main different sources: living donors, which represent a minority of donations, and deceased donors. Nevertheless, the organ shortage, which has been worsening year after year, has led to extend donation criteria over the years. This means, for example, the use of deceased donors not only after brainstem death but also after unpredictable irreversible circulatory arrest with immediate cardiopulmonary resuscitation attempted by trained providers (according to the Maastricht classification, second category) and after circulatory arrest occurring based on a decision to withhold or withdraw life-sustaining treatment (according to the Maastricht classification, third category). These death circumstances are usually associated with intensive donor reanimation processes consisting in noradrenaline administration, in massive vascular filling to prevent reanimation complications such as inflammation, haemodynamic instability or acute kidney failure. Extended criteria donors also include older donors aged over 65 years and donors with comorbidities such as arterial hypertension, cardiopathy, diabetes and even chronic kidney failure. The growing need for organs may also result in organs being transported from more distant regions. In all these situations kidney grafts are more susceptible to be affected by ischaemia‒reperfusion (IR) injuries.</p><p>IR is a pathophysiological phenomenon taking place from the donor's reanimation to the recipient's transplantation. Ischaemia is induced by the sudden arrest of oxygen and nutrients supply during the organ retrieval step, which may be prolonged during organ preservation sequence depending on its modalities. Reperfusion occurs when anastomoses are performed between the graft and the recipient and refers to the massive oxygen supply in a medium, which was previously deprived of oxygen.<span><sup>3</sup></span> On a microscopic scale, this phenomenon is associated with shifts in mitochondrial metabolism and function, by a release of reactive oxidative species causing cytoskeleton destruction, complement system activation and recruitment of innate and adaptative immune cells.<span><sup>4</sup></span> Faced with these perturbations, the cell eventually dies by necrosis, phagocytosis or apoptosis. On a ","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"5 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Involvement of S100A8 and S100A9 in nonischaemic cardiomyopathy","authors":"Qiu-Yue Lin,&nbsp;Wen-Xi Jiang,&nbsp;Hui-Hua Li","doi":"10.1002/ctd2.70039","DOIUrl":"https://doi.org/10.1002/ctd2.70039","url":null,"abstract":"<p>The heterodimeric complex of S100 calcium binding proteins A8 and A9 (S100A8/A9, also known as Calprotectin) is constitutively expressed in myeloid neutrophils and monocytes and plays a role in the modulation of the inflammatory response and cytoskeleton rearrangement. Recently, S100A8/A9 complex has garnered significant attention as a critical alarmin involved in regulating the pathogenesis of various inflammatory cardiovascular diseases, particularly nonischaemic cardiomyopathy (NICM). Furthermore, S100A8/A9 is reportedly associated with the pathophysiological processes of myocardial ischaemia‒reperfusion injury and has also been recognised as a predictor and a potential mediator of heart failure caused by acute myocardial infarction. Recent studies have attempted to provide a comprehensive and detailed overview of the involvement of the S100A8/A9 protein in NICM, covering topics such as hypertrophic myocardial remodelling, septic and dilated cardiomyopathy, myocarditis, chemotherapeutic cardiotoxicity, senescent cardiac dysfunction and cardiac allograft rejection. Ultimately, we aimed to evaluate the application of S100A8/A9 as promising biomarkers and therapeutic strategies for the prediction, prevention and treatment of NICM.</p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"5 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Commentary on ‘Lentivirus-mediated gene therapy for Fabry disease: 5-year end-of-study results from the Canadian FACTS trial’","authors":"Alessandro Rossi,&nbsp;Nicola Brunetti-Pierri","doi":"10.1002/ctd2.70038","DOIUrl":"https://doi.org/10.1002/ctd2.70038","url":null,"abstract":"&lt;p&gt;Fabry disease is an X-linked lysosomal storage disorder of glycosphingolipid catabolism caused by pathogenic variants in the &lt;i&gt;GLA&lt;/i&gt; gene encoding α-galactosidase A (α-Gal A). It is a progressive disorder with involvement of the renal, cardiac, neurologic and cerebrovascular systems, leading to reduced life expectancy.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; α-Gal A deficiency causes lysosomal accumulation of glycosphingolipids such as globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3) in the vascular endothelium, epithelial cells, podocytes, cardiomyocytes, mesangial cells and renal tubular cells. Currently available treatments for Fabry disease [enzyme replacement therapy (ERT) and chaperone therapy] are effective in mitigating the decline of renal and cardiac functions and increasing survival.&lt;span&gt;&lt;sup&gt;2, 3&lt;/sup&gt;&lt;/span&gt; However, ERT is hampered by the enzyme's short half-life, incomplete tissue penetration, infusion-related reactions, and the development of antidrug antibodies. On the other hand, oral chaperone therapy has broad tissue distribution and penetration, but its efficacy is restricted to patients carrying specific &lt;i&gt;GLA&lt;/i&gt; variants.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; Therefore, novel and more effective treatments are needed. The Fabry Disease Clinical Research and Therapeutics (FACTs) study aimed to overcome these limitations using ex vivo lentiviral vector (LV)-mediated gene transfer into autologous haematopoietic stem/progenitor cells (HSPCs) harvested from peripheral blood after mobilisation. Following non-myeloablative conditioning, genetically corrected HSPCs were infused into each patient to engraft and proliferate with all progeny cells carrying the therapeutic gene. After LV-mediated HSPC gene therapy, tissue-resident immune cells and circulating blood cells express the therapeutic gene if they are the progeny of the genetically corrected cells. The lysosomal enzyme secreted by the cells derived from genetically corrected HPSCs is then internalised by nearby and distant uncorrected cells and directed into their lysosomes for cross-correction. LV-mediated HSPC gene therapy has been used in several clinical trials including various inherited immunodeficiencies, haematological disorders, X-linked adrenoleukodystrophy, as well as other lysosomal storage disorders, such as metachromatic leukodystrophy and mucopolysaccharidosis type I.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;The FACTs trial involved five adult male individuals with classic Fabry disease. The interim results of the trial showed sustained reductions in Gb3 and lyso-Gb3.&lt;span&gt;&lt;sup&gt;6, 7&lt;/sup&gt;&lt;/span&gt; In their follow-up article, Khan and colleagues presented longer 5-year data of the FACTs study.&lt;span&gt;&lt;sup&gt;8&lt;/sup&gt;&lt;/span&gt; Importantly, no additional adverse events attributable to the gene therapy were observed and long-term α-Gal A expression along with sustained reductions in lyso-Gb3 and Gb3 continue to be observed in all study participants. Plasma and white blood cell α-Gal A ","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"5 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143521909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From multi-omics to cancer digital twins: Novel paradigm in cancer research and treatment response","authors":"Sara Sadat Aghamiri,&nbsp;Rada Amin","doi":"10.1002/ctd2.70035","DOIUrl":"https://doi.org/10.1002/ctd2.70035","url":null,"abstract":"&lt;p&gt;Integrating multi-omics in cancer research has expanded our understanding of the intricate molecular mechanisms underlying malignancies. Traditional single-omics approaches, while informative, only capture one molecular layer at a time.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; However, cancer is a multifaceted disease driven by genetic, epigenetic, metabolic and signalling interactions. In addition, the crosstalk between tumour cells and their environment, whether occurring during malignancies or modulated through therapy, is inherently multiscale. For instance, the crosstalk spans molecular-, cellular- and systems-level processes, operating across temporal and spatial scales. Such complexity renders the tumour ecosystem an archetype of a hierarchical system, requiring integrative approaches to fully comprehend and address.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Multi-omics bridges this gap by integrating diverse data types from the same patients to provide a multidimensional view of the tumour ecosystem. Each of these modalities contributes unique insights into the core tumour; for example, genomics focuses on the mutational landscape, transcriptomics highlights aberrant gene expression, proteomics elucidates protein interactions, epigenomics reveals regulatory mechanisms, metabolomics uncovers metabolic reprogramming and spatial omics map biomolecules directly onto the physical position of tumour niches.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; Together, these multiple modalities resume tumours' molecular and functional dynamics, improving applications such as precision medicine, biomarker discovery, drug target identification and patient stratification (Figure 1).&lt;/p&gt;&lt;p&gt;Integrating multi-omics requires sophisticated computational methods capable of handling high-dimensional datasets.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; To tackle these challenges, artificial intelligence (AI), machine learning (ML) and deep learning (DL) have emerged as powerful tools. The AI- and ML/DL-based models facilitate the fusion of multiple modalities into a unified framework, addressing the challenges of disparate data types that vary in size, scales, formats, distributions and noise levels. Its ability to process and harmonize multi-omics data at scale allows this approach to analyse complex datasets, identify hidden patterns and uncover correlations across multi-omics layers often imperceptible to human analysis.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; For example, Zhang et al. developed a comprehensive multi-omics platform called COMOS, designed as a non-invasive approach to enhance the diagnosis and prognosis of diffuse large B-cell lymphoma. The authors utilized cell-free DNA (cfDNA) extracted from a single tube of patient blood to analyse several features simultaneously. Using ML algorithms, authors integrated diverse parameters, including nucleosome positioning, CpG island methylation, DNase hypersensitive sites, methylated regions, and copy number alterations, providing a comprehensive view of the cfDNA landscape. COMOS demonst","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143423882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post-COVID-19 pulmonary fibrosis: Mechanisms, biomarkers, and therapeutic perspectives","authors":"Urvinder Kaur Sardarni,&nbsp;Siddappa N. Byrareddy","doi":"10.1002/ctd2.70034","DOIUrl":"https://doi.org/10.1002/ctd2.70034","url":null,"abstract":"<p>Post-COVID-19 pulmonary fibrosis (post-CPF) has emerged as a serious complication with profound implications for long-term respiratory health. This short review explores the multifactorial mechanisms underlying post-CPF, emphasising the role of oxidative stress, epithelial-to-mesenchymal transition (EMT), and dysregulated immune responses. Key signalling pathways, such as TGF-β, WNT, and Cadherin, are pivotal in fibrosis progression, offering potential therapeutic targets. Biomarkers, such as MUC4, KRT5, and ATP12A show promise for early detection and therapeutic targeting, as they share molecular features with idiopathic pulmonary fibrosis (IPF) and fibrotic interstitial lung diseases (f-ILDs), suggesting opportunities to repurpose antifibrotic therapies. Despite these advancements, significant gaps remain in understanding the cellular and molecular mechanisms underlying fibrosis progression, hindering effective management of post-CPF. Addressing these challenges through a targeted approach is critical to improving outcomes for survivors of severe COVID-19.</p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143111845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utilising single-cell sequencing in clinical nutraceutical research: Recent progress and perspectives","authors":"Xiaoqiang Wang,&nbsp;Yin S. Chan,&nbsp;David Sadava,&nbsp;Shiuan Chen","doi":"10.1002/ctd2.70032","DOIUrl":"https://doi.org/10.1002/ctd2.70032","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Single-cell sequencing technologies have revolutionised pharmaceutical research by providing in-depth insights into human biology at the single-cell level. These tools enable researchers to identify rare cell types and analyse cellular diversity within tissues, facilitating the discovery of new therapeutic targets and biomarkers. However, their application in nutraceutical research is still in its early stages.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Main Body</h3>\u0000 \u0000 <p>Unlike pharmaceuticals, which have well-defined chemical structures and mechanisms, nutraceuticals are food-based materials intended for specific medical purposes and often contain complex and diverse food chemicals. These molecules can work synergistically, producing multi-targeted effects in various tissues. Traditional bulk profiling methods for tissues and tumours do not adequately capture cellular heterogeneity or specific cellular responses to treatments. Therefore, advanced single-cell sequencing is crucial for dissecting tissues into distinct cell types, helping to clarify the underlying mechanisms at the cellular level. Many derivatives of functional foods have been marketed or assessed, demonstrating health benefits. However, mechanistic insights are lacking, with most current data derived from observational studies or traditional in vitro and in vivo models. Human clinical trials are needed to validate these nutraceutical effects and determine effective and safe dosages. Edible mushrooms have gained attention as nutraceuticals due to their medicinal properties. They have been observed to enhance immunity, reduce inflammation, and combat cancer. These effects have been attributed to their unique bioactive components and historical uses in traditional medicine. Epidemiological studies show that higher consumption of edible mushrooms is linked to a reduced risk of certain cancers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In this review, we share important lessons learned in the design and execution of clinical trials focusing on white button mushrooms as anti-cancer nutraceuticals. We demonstrate the use of single-cell RNA sequencing (scRNA-seq) in nutraceutical research to capture the nuanced biological responses and health effects of dietary foods and their constituents.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143118527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intrarenal pressure monitoring via flexible and navigable suction ureteral access sheath in retrograde intrarenal surgery: A preclinical animal study and a pilot clinical study","authors":"Wei Zhu,&nbsp;Steffi Kar Kei Yuen,&nbsp;Jianwei Cao,&nbsp;Chu Ann Chai,&nbsp;Shusheng Liu,&nbsp;Jingzeng Du,&nbsp;Wen Zhong,&nbsp;Zhijian Zhao,&nbsp;Yongda Liu,&nbsp;Guohua Zeng","doi":"10.1002/ctd2.70031","DOIUrl":"https://doi.org/10.1002/ctd2.70031","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Elevated intrarenal pressure (IRP) during retrograde intrarenal surgery (RIRS) can lead to deleterious complications. Emerging non-invasive, real-time IRP monitoring tools are proving crucial for enhancing procedural safety. This study evaluates a newly developed flexible and navigable suction ureteral access sheath (FANS) with IRP monitoring capabilities through animal study and a clinical trial, assessing its accuracy and operational benefits.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A preclinical animal study and a prospective clinical trial involving 100 patients were conducted. The animal study confirmed the accuracy of IRP-monitoring FANS, whilst the clinical trial compared its performance to conventional FANS in RIRS. The evaluated outcomes included the accuracy of IRP measurements, the irrigation flow rate, the duration of the operation, and the stone-free rate (SFR). Statistical comparisons were performed using appropriate tests with a significant threshold of <i>p</i> &lt; .05. Registration for this study is recorded under the identifier NCT06729801 at ClinicalTrials.gov.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the animal study, IRP-monitoring FANS demonstrated high accuracy in real-time IRP measurement, comparable to percutaneous nephrostomy-based monitoring. In the clinical study, IRP-monitoring FANS enabled increased irrigation flow whilst maintaining safe IRP levels within 30 mmHg. Operative time was significantly shortened in IRP-monitoring FANS group (50.9 vs. 67.6 min, <i>p</i> &lt; .01), with similar SFRs between groups. No notable discrepancies in the rates of complications were observed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The IRP-monitoring FANS improves stone retrieval efficiency and shortens operative time whilst ensuring safety through real-time IRP monitoring. This novel device marks a major improvement in both the safety and effectiveness of RIRS for managing large renal stones.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70031","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143117827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utilisation of a national database to characterise renal function in patients with COVID19 infection","authors":"Nicholas R. Nelson,&nbsp;Nicholas Farina,&nbsp;Denise H. Rhoney,&nbsp;the N3C consortium","doi":"10.1002/ctd2.70027","DOIUrl":"https://doi.org/10.1002/ctd2.70027","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Rationale</h3>\u0000 \u0000 <p>The incidence of renal function alterations among patients with COVID19 is unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To determine the incidence of acute kidney injury (AKI) or augmented renal clearance (ARC) in patients hospitalised with COVID19 and identify risk factors for patients who may exhibit each renal alteration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Retrospective, observational cohort analysis of hospitalise, adult patients within the National COVID Cohort Collaborative (N3C) database with laboratory confirmed COVID19 and available data to calculate creatinine clearance using the Cockcroft–Gault equation from 1 January 2020 through 9 April 2022.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Measurements</h3>\u0000 \u0000 <p>Incidence of AKI or ARC and patient demographics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Main results</h3>\u0000 \u0000 <p>15 608 patients were included for renal function characterisation where 20.9% experienced AKI and 34.8% exhibited ARC. ARC lasted longer than AKI; however, AKI was associated with increased hospital length of stay and mortality. 11 274 patients were included in logistic regression analysis. Height and White race were the only variables associated with decreased risk of AKI while male sex and diabetes were associated with increased risk. Male sex, Black race and hypertension were associated with decreased risk of ARC. Age was associated with decreased risk of both AKI and ARC while weight and Hispanic ethnicity were associated with increased risk in both renal alterations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>A significant proportion of patients exhibit renal alterations during their hospitalisation for COVID19. These results provide initial evidence of identifying patients at risk of AKI or ARC, but more research is needed, especially with respect to use of biomarkers for renal alteration risk stratification.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143113677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thyroglobulin mRNA ectopic expression was an excellent marker to detect lymph node metastasis for patients with papillary thyroid cancer","authors":"Wen-Hua Du,&nbsp;Ying-Chao Chen,&nbsp;Ning Jin,&nbsp;Yuan-yuan Zhang,&nbsp;Bao-Lan Ji,&nbsp;Jing Wu,&nbsp;Feng-Yao Wu,&nbsp;Shuang-Xia Zhao,&nbsp;Bing Han,&nbsp;Huai-Dong Song,&nbsp;Mei Dong","doi":"10.1002/ctd2.70029","DOIUrl":"https://doi.org/10.1002/ctd2.70029","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To investigate whether the mRNA expression of thyroglobulin (<i>TG</i>) and TSH receptor (<i>TSHR</i>) in lymph node could be used to diagnose lymph node metastasis in patients with papillary thyroid cancer (PTC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Subjects and methods</h3>\u0000 \u0000 <p>Around 156 paraffin samples of lymph nodes from 89 patients with PTC after surgery were collected, and the expressions of <i>TG</i> and <i>TSHR</i> mRNA were detected by nested qPCR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared with the results of confirmed histopathology, 86 out of 87 tissues of lymph nodes metastasis ectopically expressed <i>TG</i> mRNA, while 66 out of 69 tissues of non-metastasis lymph nodes did not express the <i>TG</i> mRNA. The specificity and sensitivity of <i>TG</i> mRNA measurement for detecting the lymph node metastasis were 95.65% and 98.85%, as effective as the first postoperative histopathology. However, the specificity and sensitivity of <i>TSHR</i> mRNA measurement were 92.75% and 85.06%, respectively. The accuracy of <i>TG</i>, <i>TSHR</i> mRNA measurement and the first postoperative histopathology were 97.44%, 88.46% and 95.51%, with the positive predictive rate (PPR) 96.63%, 93.67%, and 98.78%, respectively, negative predictive rate (NPR) 98.51%, 83.12% and 91.89%, respectively, as well as Youden's index 0.95, 0.78 and 0.92.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p><i>TG</i> mRNA ectopic expression in the lymph node might be an excellent marker to diagnose the lymph node metastasis for patients with PTCs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143113496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}