Clinical and translational discovery最新文献

{"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}

{"title":"Recent advances in mitochondrial replacement therapy and its future expectations","authors":"Qifeng Lyu,&nbsp;Weiwei Zou,&nbsp;Taosheng Huang","doi":"10.1002/ctd2.70010","DOIUrl":"https://doi.org/10.1002/ctd2.70010","url":null,"abstract":"<p>The prevention of mitochondrial diseases is particularly important due to the lack of specific therapies. Therefore, mitochondrial replacement therapy (MRT) is expected to be a technology to prevent mitochondrial diseases. Admittedly, this technology sparked a lot of controversy and discussion. In this article, we review the recent advances in MRT, discuss its safety and ethical issues, and finally explore its potential to completely block the inheritance of mitochondrial diseases.</p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143112299","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":"Roads diverged in a wood: Proteins and RNAs encoded by cytochrome b (CYTB) gene in health and disease","authors":"Cijie Du,&nbsp;Baodan Chen,&nbsp;Yile Huang,&nbsp;Wenxi Liang,&nbsp;Ying Hua Su,&nbsp;Xingguo Liu","doi":"10.1002/ctd2.70026","DOIUrl":"https://doi.org/10.1002/ctd2.70026","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The cytochrome b (<i>CYTB</i>) gene, a crucial component of the mitochondrial genome, plays a multifaceted role in cellular metabolism, energy production and various biological processes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Main body</h3>\u0000 \u0000 <p>It is well known that the <i>CYTB</i> gene encodes a subunit of complex III in the electron transport chain, which is vital for the oxidative phosphorylation process and ATP generation. Various studies report that the <i>CYTB</i> gene not only encodes a core protein in the mitochondrial respiratory chain but also produces a long non-coding RNA called lncCYTB, which participates in a variety of physiological and pathological processes. Inspiringly, a study has recently revealed that the <i>CYTB</i> gene also encodes a novel 187 amino acid long polypeptide, CYTB-187AA, a mitochondrial DNA-encoded protein produced by cytosolic translation and important for early mammalian development.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This review will provide insight into the functional and expression properties of the <i>CYTB</i> gene, as well as its unique non-coding RNA signature, and describe the diseases associated with the <i>CYTB</i> gene, ranging from mitochondrial dysfunction to more complex genetic disorders.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143111064","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":"The FACTs trial for Fabry disease highlights the promise and challenges of gene therapy","authors":"Jeffrey A. Medin,&nbsp;Michael L. West","doi":"10.1002/ctd2.70028","DOIUrl":"https://doi.org/10.1002/ctd2.70028","url":null,"abstract":"&lt;p&gt;Gene therapy studies in Fabry disease (FD) are proceeding utilising either lentivirus (LV) or adeno-associated virus (AAV) vectors with either ex vivo or in vivo transductions, respectively. In the FACTs (Fabry Disease Clinical Research and Therapeutics) gene therapy trial,&lt;span&gt;&lt;sup&gt;1, 2&lt;/sup&gt;&lt;/span&gt; five male patients with classical FD (aged 29–48 years) received autologous LV-transduced CD34+ haematopoietic stem/progenitor cells (HSPCs). Cells were transduced ex vivo with a recombinant LV harbouring the cDNA for human α-galactosidase A (α-gal A) and returned to non-myeloablated hosts who had received low-dose melphalan. Cells engrafted well and polyclonal haematopoiesis was observed.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; In FD, as with a number of lysosomal storage disorders (LSDs), the overexpressed hydrolase can be used by primary corrected cells and can also be secreted, enabling uptake via a mannose-6-phosphate receptor into bystander cells. This was the rationale for targeting HSPCs as they, and their progeny, can circulate and thereby deliver the corrective enzyme systemically. In contrast to enzyme therapy (ET), this approach utilised a single infusion rather than continual biweekly treatments. This single infusion of LV-transduced cells led to continuous production of the α-gal A&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; rather than variable peaks and troughs of activity as is seen with ET. The promise and challenges in gene therapy for amelioration of single-gene defects are highlighted by this study (See Figure 1).&lt;/p&gt;&lt;p&gt;The 5-year data show that this LV-based gene therapy was safe and impactful.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Four of the five patients went home the same day as their cell infusions. Febrile neutropenia was observed in one patient; another developed a PICC line infection. These were the only two severe adverse events. All patients achieved sufficient α-gal A activity that they technically did not have FD and were eligible to pause their ET. Three patients stopped ET and remained off for between 3 and 5 years duration. Other benefits were also observed: three of the patients had IgG-based antibody titres against α-gal A. In each case, these titres were reduced to background following the gene therapy and remained there for all 5 years. This was likely due to the conditioning regimen or to tolerisation generated by continual production of low levels of α-gal A from LV-transduced cells. Plasma globotriaosylsphingosine, an important biomarker, was also decreased in four of five patients. Further, estimated glomerular filtration rate, proteinuria and left ventricular mass index stabilised in most patients.&lt;/p&gt;&lt;p&gt;After 5 years, no haematopoietic (or any other) malignancies have been seen in our study. This mirrors data to March 2022 in the entire gene therapy field when recombinant LV were employed.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; However, three recent trials contrast this situation.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; Haematological cancers developed in seven out of 67 pat","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143110950","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":"Exosomes and machine perfusion as a therapy to improve organ transplantation","authors":"Wayne J. Hawthorne,&nbsp;Rajith Amaratunga,&nbsp;Ahmer Hameed","doi":"10.1002/ctd2.70025","DOIUrl":"https://doi.org/10.1002/ctd2.70025","url":null,"abstract":"&lt;p&gt;Cellular therapies are cutting-edge technologies that are now expanding into all spheres of medicine including transplantation. We are increasingly reliant upon marginal or less optimal donor organs for transplantation, however, to close the ever-widening gap between organ demand and supply. Such organs have higher discard rates and less ideal short and longer-term outcomes and ideally require improved organ preservation and resuscitation methods which can be utilised regardless of the jurisdiction.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Various cellular therapies are gaining significant momentum as a novel approach to reducing transplant organ ischemia/reperfusion injury (IRI), and potential improvement in graft outcomes. As seen in Figure 1, machine perfusion of organs provides the ideal setting to specifically deliver many targeted therapies to individual grafts, including therapies such as; stem cells, organoids, viral transduction, nanoparticles, and the use of exosome-based treatments.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Exosomes are small extracellular vesicles (30–150 nm in diameter), that play a unique role in cellular communication, derived from the endosomal pathway, with intraluminal vesicles being formed in multivesicular bodies and subsequently released with fusion of the plasma membrane. Unlike traditional cell-based therapies, exosomes do not contain live cells, reducing concerns about immune interaction in both the organ and subsequently recipient. In the study by Burdeyron et al.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; innovatively delivered exosomes derived from porcine urine progenitor cells (UPCs) to kidneys using hypothermic and normothermic machine perfusion (HMP and NMP).&lt;/p&gt;&lt;p&gt;IRI is a critical challenge in transplantation, particularly impacting organs from extended criteria donors and those from donors after circulatory death. These types of organs are generally more sensitive to ischemia, with attendant magnification of injury during reperfusion, and a subsequent higher incidence of graft dysfunction/rejection.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; Technologies such as HMP and NMP are variably employed by different centres to improve organ quality prior to transplantation. HMP involves the continuous circulation of a cold preservation solution through the kidney, whilst NMP involves perfusing the kidney with a warm, oxygenated solution to simulate physiological conditions. While these methods offer some protective effects, they do not completely ameliorate IRI, and significant further work is required to enhance their efficacy.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Exosomes carry bioactive molecules, including microRNAs (miRNAs), mRNAs, and proteins, which can influence cellular interaction and regulate immune activity. Exosome-based therapy can leverage the potential for intercellular communication, signalling cascades, and other physiological effects without the complexity and risks associated with administering whole cells. Studies have shown that exosomes derived f","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143118160","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":"Molecular mechanisms underlying oesophageal cancer development triggered by chronic alcohol consumption","authors":"Huai Yi Chen,&nbsp;Chia Rou Por,&nbsp;Yong Kai Hong,&nbsp;Eason Qi Zheng Kong,&nbsp;Vetriselvan Subramaniyan","doi":"10.1002/ctd2.70021","DOIUrl":"https://doi.org/10.1002/ctd2.70021","url":null,"abstract":"<p>This review explores the mechanisms underlying alcohol-induced oesophageal carcinogenesis, including DNA damage, oxidative stress, and nutritional deficiencies. Alcohol metabolism primarily involves alcohol dehydrogenase (ADH) converting ethanol to acetaldehyde, which can cause DNA damage, inhibit repair mechanisms, and form DNA adducts thus inhibiting DNA replication. Plus, it delves into the epidemiological evidence, genetic susceptibility, epigenetic modifications, biomarkers, and preventive strategies associated with alcohol-related oesophageal cancers. Consumption of alcohol increases the risk of gastroesophageal reflux disease thus compromising mucosal integrity of the oesophagus as dysregulation of cytokines such as IL-18, TNFA, GATA3, TLR4, and CD68 expands the intercellular spaces of epithelial cells. Genetic variants, such as ADH1B rs1229984 and ALDH2 rs671, significantly influence susceptibility to alcohol-related oesophageal cancers, with these variations affecting acetaldehyde metabolism and cancer risk. Understanding these factors is crucial for early detection, effective treatment, and the development of targeted prevention strategies. Biomarkers, such as miRNA and metabolite markers, offer non-invasive methods for early detection, while advanced endoscopic techniques provide better diagnostic accuracy. Pharmacological interventions, such as statins and proton pump inhibitors, also show potential for reducing cancer progression in high-risk individuals. Despite advances, late-stage oesophageal cancer diagnoses are still common, highlighting the need for better screening and prevention. Further research, including this study, should aim to improve early detection, personalise prevention, and explore new treatments to reduce cases and enhance outcomes in alcohol-related oesophageal cancers.</p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142860041","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":"An auxiliary diagnostic approach based on traditional Chinese medicine constitutions for older patients with frailty","authors":"Xuchao Gu,&nbsp;Xiaojun Wang,&nbsp;Yijing Yang,&nbsp;Kangwei Guan,&nbsp;Hung-Chen Chang,&nbsp;Dehua Liu,&nbsp;Wenhao Wang,&nbsp;Tao Wu,&nbsp;Peiqing He,&nbsp;Jiaofeng Wang,&nbsp;Jie Chen,&nbsp;Zhijun Bao","doi":"10.1002/ctd2.70019","DOIUrl":"https://doi.org/10.1002/ctd2.70019","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>As global population ages, frailty has surfaced as a major public health challenge. Given the heterogeneity of frailty in the clinical presentation, it is imperative to develop personalised diagnostic and treatment strategies. The traditional Chinese medicine (TCM) constitution offers notable advantages in discerning individual differences. This study aims to elucidate the association between TCM constitutions and frailty, providing insights into the application of TCM for the frailty management.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>An observational study was conducted at Huadong hospital from July 2022 to November 2023. A total of 241 older patients were recruited. Each patient underwent assessments for the TCM constitution and frailty status. Comprehensive data collection encompassed medical history, biochemical indicators, bone mineral density (BMD), body composition and physical performance metrics. Plasma samples were also collected to detect levels of inflammatory factors and lymphogenesis-related factors, including IL-1β, TNF-α, VEGF-C, ANGPTL4 and ACV-A. Multi-level statistical analysis was used to establish the relationship of TCM constitutions with frailty.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Amongst all participants, 54 individuals were classified as non-frail, 90 individuals as pre-frail and 97 individuals as frail. Regression analysis indicated that frailty was closely associated with four imbalanced TCM constitutions: Qi deficiency, phlegm dampness, blood stasis and Qi depression. Subsequent analysis demonstrated that Qi deficiency was associated with decreased BMD, phlegm dampness with elevated high-density lipoprotein levels, Blood stasis with elevated blood glucose levels, and Qi depression with both decreased BMD and elevated low-density lipoprotein levels. Furthermore, individuals characterised by imbalanced TCM constitutions exhibited inferior handgrip strength, walking pace, lower limb strength and higher levels of inflammatory factors and lymphogenesis-related factors compared to those with balanced TCM constitution.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Frailty is independently associated with Qi deficiency, phlegm dampness, blood stasis and Qi depression. Personalised diagnostic approaches based on the TCM constitution may offer valuable insights for directing treatment for older patients with frailty.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708345","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":"Application of machine learning-based phenotyping in individualized fluid management in critically ill patients with heart failure","authors":"Chengjian Guan,&nbsp;Bing Xiao","doi":"10.1002/ctd2.70020","DOIUrl":"https://doi.org/10.1002/ctd2.70020","url":null,"abstract":"&lt;p&gt;Heart failure (HF) is a major public health challenge, with fluid management being one of the most critical aspects of treatment. Fluid management is particularly a complex and challenging issue in critically ill patients, especially when cardiac pump function fails to meet the body's needs.&lt;span&gt;&lt;sup&gt;1-3&lt;/sup&gt;&lt;/span&gt; Clinicians often face multiple challenges when formulating fluid management strategies, including significant individual variations, complex dynamic changes, and diverse monitoring indicators. Most current intervention studies targeting fixed fluid management in HF patients have reported negative outcomes,&lt;span&gt;&lt;sup&gt;4, 5&lt;/sup&gt;&lt;/span&gt; reflecting the heterogeneity of severe HF patients and highlighting the urgent need for precision medicine. Therefore, our study aims to identify distinct characteristics of critically ill HF patients through retrospective analyses and develop targeted treatment strategies based on the optimal fluid balance ranges identified by longitudinal infusion data for each patient phenotype (Figure 1).&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;The advancement of artificial intelligence and machine learning (ML) technology offers innovative solutions to these challenges. Unsupervised ML has emerged as a powerful tool in medical research, capable of identifying patterns in complex, high-dimensional data without explicit labelling. The patient data were extracted from two intensive care unit databases, integrating both numerical and categorical variables to maintain comprehensive clinical characteristics. The K-Prototypes algorithm was selected for its ability to effectively combine the principles of K-Means and K-Modes principles, thereby enhancing clustering quality by considering the differential contributions of various variable types to the total distance between samples.&lt;span&gt;&lt;sup&gt;7&lt;/sup&gt;&lt;/span&gt; Furthermore, fluid management is a dynamic process, where daily interventions and test results can affect subsequent outcomes. To address this, we analyzed 7-day fluid balance records using the G-formula parameter.&lt;span&gt;&lt;sup&gt;8&lt;/sup&gt;&lt;/span&gt; a sophisticated statistical approach to eliminate confounding effects between time-varying exposures and outcomes, thus providing more reliable clinical guidance.&lt;/p&gt;&lt;p&gt;Our analysis identified four distinct phenotypes of HF patients, each exhibiting significant differences in clinical characteristics and prognosis. The optimal fluid balance ranges for each phenotype aligned closely with their distinct clinical features. Phenotype A, characterized by severe inflammation and aggressive interventions including high rates of vasoactive drug use and mechanical ventilation, showed optimal outcomes with a moderate fluid balance of between –1000 and 500 mL per day. This finding indicates that a positive fluid balance is associated with adverse effects on mechanical ventilation duration and mortality. Phenotype C, despite having milder clinical parameters but combined with advanced age and multiple c","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708343","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":"Use of short-term cervical collars is associated with emotional discomfort","authors":"Abha Somesh,&nbsp;Jackson Catalano,&nbsp;Andrew Underhill,&nbsp;Jessica Hocking,&nbsp;Evan Symons,&nbsp;Biswadev Mitra","doi":"10.1002/ctd2.70016","DOIUrl":"https://doi.org/10.1002/ctd2.70016","url":null,"abstract":"&lt;p&gt;We read with interest the manuscript on the topic of cervical collars for the management of spinal cord injuries.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Kolli et al. provide compelling evidence on the low levels of evidence for cervical collars to restrict movement and prevent worsening injury. On the contrary, evidence towards delayed recovery and worse pain profiles suggest adverse effects from collar use.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;The association of long-term collar use with poorer quality of life was highlighted.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; especially in older adults.&lt;span&gt;&lt;sup&gt;2, 3&lt;/sup&gt;&lt;/span&gt; However, patient experiences of wearing cervical collars for shorter times in an emergency department (ED) setting have not been previously evaluated. The current standard of care in Victoria, Australia is the use of rigid foam cervical collars for spinal immobilisation in a patient with suspected cervical spine injury.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;We conducted a pilot prospective cohort study at an adult major trauma centre in Australia which records approximately 10 000 trauma presentations a year. The aim of this study was to evaluate patients’ experiences in a short-term cervical collar and the purpose of the study was to generate a hypothesis of harm. Short-term was defined as the period between application of the collar and until being cleared of any cervical spine injuries, which is less than 12 h.&lt;/p&gt;&lt;p&gt;A total of 20 participants enrolled by convenience sampling who were managed in cervical collars awaiting clearance with a Glasgow Coma Scale rating of 15, and who could converse in English formed the exposure group. A non-exposure group of 20 participants included adult patients not in cervical collars awaiting the results of investigations in the ED. All 40 participants were admitted to the short-stay unit in the ED with an aim to be discharged home in 24 h which suggests they all had low disease severity. The groups were matched for age (± 2 years) and gender. All 40 participants were assessed at a single time point using the Patient Evaluation of Emotional Comfort Experience (PEECE) questionnaire.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; This tool evaluates positive mental well-being elements like emotional comfort rather than negative health outcomes.&lt;/p&gt;&lt;p&gt;Each component of the PEECE score and the total were summarised using medians (inter-quartile range) and differences were compared using the Wilcoxon Rank Sum test. A &lt;i&gt;p&lt;/i&gt;-value of &lt;.05 was defined to be statistically significant. All analyses were conducted using Stata v18.0.&lt;/p&gt;&lt;p&gt;The total PEECE score among patients with a collar was 30.5 (interquartile range [IQR] 21–39.5), significantly lower than patients without a collar (total score 38.5; IQR 32–41.5, &lt;i&gt;p&lt;/i&gt; = .016) (Figure 1). With a collar in place, patients reported significantly lower scores for positive emotions of being at ease, relaxed or wanting to smile. In addition, they also scored significantly lower perceptions of being valued, f","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142641392","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":"Challenges and advances of immune checkpoint therapy","authors":"Lingyu Li,&nbsp;Yingli Sun","doi":"10.1002/ctd2.70001","DOIUrl":"https://doi.org/10.1002/ctd2.70001","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Objectives</h3>\u0000 \u0000 <p>Immuno-checkpoint therapy (ICT) significantly alters the clinical course of cancer patients, providing long-lasting clinical benefits and offering the potential for cure to some patients. However, response rates for different tumour types vary, and predictive biomarkers are needed to enhance patient selection for the purpose of optimising effectiveness and reducing toxicity. This has driven efforts to decipher the immune and non-immune factors that regulate ICT response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Main Content</h3>\u0000 \u0000 <p>This review offers a thorough examination of the advantages and future challenges of immune checkpoint inhibitors in cancer therapy. Additionally, we explore ongoing efforts to address current challenges, such as guiding subsequent clinical trials, developing ICT combination therapy strategies and utilising epigenetics to enhance clinical efficacy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion and Perspectives</h3>\u0000 \u0000 <p>Despite significant progress, ICT faces challenges including immune-related adverse events (irAEs) and resistance mechanisms. Ongoing research focuses on developing novel biomarkers, combination therapies, and epigenetic strategies to improve the efficacy and safety of ICT for cancer patients worldwide. Future studies are required to validate these findings across different tumor types and treatment settings.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142587927","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}