Jung-Taek Kang, Joo-Hee Park, Mi-Young Jung, Pu-Hyeon Cha, Choul Yong Park
{"title":"Development of stromal corneal grafts using a novel decellularization method with sodium cocoyl glutamate on <i>GGTA1</i>/<i>CMAH</i>/<i>β4GalNT2</i> knock-out porcine corneas.","authors":"Jung-Taek Kang, Joo-Hee Park, Mi-Young Jung, Pu-Hyeon Cha, Choul Yong Park","doi":"10.21037/atm-25-3","DOIUrl":"10.21037/atm-25-3","url":null,"abstract":"<p><strong>Background: </strong>Diseases of the human cornea often necessitate corneal transplantation. However, donor corneas are not always readily available, leaving many patients waiting for donated corneas. Porcine corneas are a promising alternative to human donor corneas due to their close anatomical and physiological similarities. In this study, we produced <i>GGTA1</i>/<i>CMAH</i>/<i>β4GalNT2</i> knockout pigs [triple knockout (TKO)] to minimize immune rejection. We investigated the efficacy and safety of a novel corneal decellularization process using sodium cocoyl glutamate (SCG) and supernuclease (SN).</p><p><strong>Methods: </strong>We harvested cornea stromal grafts from 2-month-old TKO pigs, decellularized them using SCG and SN. The optical transparency, DNA content, collagen content, glycosaminoglycan content, and tensile strength of the decellularized corneas were measured. The <i>in vivo</i> safety and efficacy of the decellularized corneas were evaluated by transplanting them into the stromal pockets of rabbit corneas. Comparisons between wild type (WT) and TKO corneas, both decellularized and non-decellularized, were performed over a 4-week period post-transplantation.</p><p><strong>Results: </strong>Compared to a previous method using sodium N-lauroyl glutamate (SLG), the method using 0.5% SCG and SN more effectively removed DNA from the corneal stroma without significantly changing tensile strength, transparency, collagen, or glycosaminoglycan content. When decellularized corneas were implanted into corneal stromal pockets of rabbits, at 4 weeks post-surgery, decellularized corneas from WT pigs showed significant corneal neovascularization and opacity. In contrast, those from TKO pigs with 0.5% SCG plus SN decellularization maintained good transparency with minimal vascularization.</p><p><strong>Conclusions: </strong>Corneas from TKO pigs could be successfully decellularized using 0.5% SCG plus SN method, showing promising results after transplanting them into rabbit corneas.</p>","PeriodicalId":8216,"journal":{"name":"Annals of translational medicine","volume":"13 3","pages":"28"},"PeriodicalIF":0.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12272801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jonathan Day, Juliana S Lee, Jeffrey J Stewart, Hannah K Paul-Warburton, Bryan W Cunningham
{"title":"An investigational time-course study using an <i>in vivo</i> ovine laminectomy model for the neurohistopathological evaluation of hemostatic agents.","authors":"Jonathan Day, Juliana S Lee, Jeffrey J Stewart, Hannah K Paul-Warburton, Bryan W Cunningham","doi":"10.21037/atm-25-10","DOIUrl":"10.21037/atm-25-10","url":null,"abstract":"<p><strong>Background: </strong>Preclinical <i>in vivo</i> analysis of hemostatic agents is a fundamental requirement in the assessment of implant safety and efficacy prior to utilization in the clinical operative setting. The purpose of this study served to investigate the hemostatic, peri-operative outcomes and histopathologic responses following epidural application of a novel hemostatic agent in an ovine lumbar laminectomy model. Despite routine utilization of hemostatic agents, the potential for inflammation and compression of neural structures, fibrosis, and neurotoxicity remains a clinical concern. Epidural fibrosis resulting from hemorrhage creates chronic pain and is often refractory to treatment. Experimental endpoints, including intraoperative hemostasis, perioperative neurologic assessment, clinical pathology, and neurohistopathology, were used to evaluate the translational efficacy of this model.</p><p><strong>Methods: </strong>Nine healthy crossbred Suffolk sheep (skeletally mature females, 1.5-2 years old, approximately 150 pounds) underwent posterior surgical lumbar laminectomies at the L3 and L5 levels followed by epidural application of a novel hydrophobically modified chitosan-based hydrogel hemostatic agent (test article). The Surface Bleeding Severity Scale (SBSS) score was recorded immediately after completion of the laminectomy at baseline, and then at 3-, 6-, and 10-minute intervals following application of the hemostatic agent. Postoperative survival analysis, specifically focused on animal recovery and neurological status was performed. Clinical pathology including comprehensive vet screens (CVS), complete blood count (CBC) with differential, and cerebrospinal fluid (CSF) assays were completed. Animals were humanely sacrificed at 12 days (n=6), 30 days (n=1), 60 days (n=1), and 90 days (n=1). Necropsy was performed at the time of sacrifice and the operative levels were axially sectioned for histopathologic evaluation.</p><p><strong>Results: </strong>There were no neurologic, vascular, or infectious complications and animals exhibited normal recovery for this 2-level laminectomy surgical model. Complete intraoperative hemostasis was achieved in 16 out of 18 operative levels by the 3-minute interval and all 18 laminectomy levels demonstrated complete hemostasis by the 6-minute interval. Clinical pathology results were unremarkable. Histological characterization exhibited normal inflammatory and healing responses of the tissues at all postmortem time points, without evidence of abnormal spinal cord changes or infection. Residual test article was observed to decrease between the 30- and 60-day intervals, with no residual material in the epidural space observed at 90 days.</p><p><strong>Conclusions: </strong>This pilot study demonstrates the translational utility of the ovine model in evaluating the safety and efficacy of a novel hemostatic agent in the lumbar spine. Based on these early findings in intraoperative hemostasis,","PeriodicalId":8216,"journal":{"name":"Annals of translational medicine","volume":"13 3","pages":"27"},"PeriodicalIF":0.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12272799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Miguel Muniz, Daniel S Childs, Jack Andrews, Ahmed M Mahmoud, Sean Park, Oliver Sartor, Adam M Kase, Irbaz B Riaz, Bradley J Stish, Aadel A Chaudhuri, Pradeep S Chauhan, Ryan Phillips, Fabrice Lucien, Jacob J Orme
{"title":"Deferral of systemic therapy in patients with oligorecurrent prostate cancer treated with metastasis-directed radiotherapy.","authors":"Miguel Muniz, Daniel S Childs, Jack Andrews, Ahmed M Mahmoud, Sean Park, Oliver Sartor, Adam M Kase, Irbaz B Riaz, Bradley J Stish, Aadel A Chaudhuri, Pradeep S Chauhan, Ryan Phillips, Fabrice Lucien, Jacob J Orme","doi":"10.21037/atm-24-187","DOIUrl":"10.21037/atm-24-187","url":null,"abstract":"<p><p>Distant metastasis marks a critical transition in prostate cancer, separating potentially curable from canonically incurable disease. Oligometastatic disease, defined as limited metastases (e.g., less than 3, 5, or 10), can encompass different clinical scenarios, including oligorecurrent disease (characterized by a limited number of metastatic lesions that recur after initial definitive treatment), and has emerged as an intermediate or transitional state. While intensified systemic therapies are increasingly applied to metastatic cases, many patients prefer to delay starting castrating therapies. Metastasis-directed therapy (MDT) is a safe and effective alternative to systemic therapy in a subset of patients with well-defined oligometastatic disease. Recent advances in imaging technologies and emerging treatment paradigms pose clinical challenges for patient risk stratification and optimal treatment selection. Here, we explore two key developments in the field: the influence of advanced imaging on clinical decision-making and the growing role of radiotherapy (RT) in oligometastatic disease management. We explore the landscape of novel biomarkers to estimate micrometastatic disease burden, which eludes imaging, using the concept of \"liquid tumor burden\" (LTB) measured by blood-based markers like circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and tumor-derived extracellular vesicles (tdEVs). Promising data suggest that LTB assessment may refine patient selection for MDT and systemic treatment. These findings suggest potential for a combined approach of MDT and systemic therapy in oligometastatic prostate cancer (omPC).</p>","PeriodicalId":8216,"journal":{"name":"Annals of translational medicine","volume":"13 3","pages":"29"},"PeriodicalIF":0.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12272797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Erratum to Phosphorylated nuclear factor erythroid 2-related factor 2 promotes the secretion of C-C motif chemokine ligand 2 and the recruitment of M2 macrophages.","authors":"","doi":"10.21037/atm-2024-17","DOIUrl":"10.21037/atm-2024-17","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.21037/atm-21-2947.].</p>","PeriodicalId":8216,"journal":{"name":"Annals of translational medicine","volume":"13 3","pages":"35"},"PeriodicalIF":0.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12272791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Iago Pinal-Fernandez, Maria Casal-Dominguez, Andrew L Mammen
{"title":"Dazukibart for dermatomyositis: expanding the therapeutic arsenal.","authors":"Iago Pinal-Fernandez, Maria Casal-Dominguez, Andrew L Mammen","doi":"10.21037/atm-25-44","DOIUrl":"10.21037/atm-25-44","url":null,"abstract":"","PeriodicalId":8216,"journal":{"name":"Annals of translational medicine","volume":"13 3","pages":"24"},"PeriodicalIF":0.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12272793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Matthew Van Oirschot, Saurav Verma, Daniel Breadner, Andrea Vucetic
{"title":"Raltitrexed as a substitute for 5-fluorouracil in combination with pembrolizumab and platinum in a patient with metastatic esophageal squamous cell carcinoma and coronary artery disease: a case report.","authors":"Matthew Van Oirschot, Saurav Verma, Daniel Breadner, Andrea Vucetic","doi":"10.21037/atm-25-38","DOIUrl":"10.21037/atm-25-38","url":null,"abstract":"<p><strong>Background: </strong>Chemoimmunotherapy is the standard treatment for patients with metastatic esophageal squamous cell carcinoma (ESCC), for which 5-fluorouracil (5-FU) is commonly part of the chemotherapy regimen. Given that 5-FU has a mean cardiotoxicity risk of approximately 5%, raltitrexed has often been used as an alternative in patients with a history of fluoropyrimidine-associated cardiotoxicity or significant coronary artery disease (CAD). We report the first case, to our knowledge, of the use of raltitrexed in place of 5-FU in combination with pembrolizumab and platinum-based chemotherapy for the treatment of metastatic esophageal cancer in a patient with CAD.</p><p><strong>Case description: </strong>A 75-year-old gentleman with preexisting multivessel CAD was diagnosed with metastatic gastroesophageal junction (GEJ) squamous cell carcinoma (SCC) after presenting to medical attention with a 2-month history of worsening chest pain in addition to progressive dysphagia associated with weight loss. Following initial treatment with palliative locoregional radiotherapy to the lower mediastinum, GEJ, and upper abdomen, the decision was made to proceed with palliative systemic therapy. Considering his significant cardiac history, 5-FU was replaced with raltitrexed and combined with carboplatin and pembrolizumab. After a total of 10 months of treatment, the patient presented to hospital with recurrent chest pain and was diagnosed with a non-ST-elevation myocardial infarction (NSTEMI). Despite radiographic evidence of stability of his malignancy on systemic therapy, he was not considered to be a candidate for cardiac intervention. He was thus transitioned to a comfort-focused care approach and passed away shortly thereafter, with the cause of death being acute coronary syndrome.</p><p><strong>Conclusions: </strong>Although the patient unfortunately passed away prematurely due to preexisting CAD, there was no evidence of disease progression in the 10 months that he received treatment. In addition to an encouraging progression-free survival (PFS), the patient reported an overall improvement in quality of life while on therapy with no signals of toxicity from raltitrexed or immunotherapy. Overall, the present case demonstrates that chemotherapy in combination with immunotherapy for the treatment of advanced esophageal cancer appears to be safe and effective when raltitrexed is substituted for 5-FU, which is of particular relevance due to the many overlapping characteristics of patients with cardiac pathology and esophageal cancer.</p>","PeriodicalId":8216,"journal":{"name":"Annals of translational medicine","volume":"13 3","pages":"32"},"PeriodicalIF":0.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12272798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Early restrictive versus liberal oxygen for trauma patients: does it make a difference?","authors":"Colin F Mackenzie","doi":"10.21037/atm-25-33","DOIUrl":"10.21037/atm-25-33","url":null,"abstract":"","PeriodicalId":8216,"journal":{"name":"Annals of translational medicine","volume":"13 2","pages":"12"},"PeriodicalIF":0.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Olverembatinib for heavily pretreated <i>BCR::ABL1</i>-positive leukemia, including resistance or intolerance to ponatinib and/or asciminib.","authors":"Yasushi Kubota","doi":"10.21037/atm-25-28","DOIUrl":"10.21037/atm-25-28","url":null,"abstract":"","PeriodicalId":8216,"journal":{"name":"Annals of translational medicine","volume":"13 2","pages":"13"},"PeriodicalIF":0.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106115/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Promising results with the daily oral small molecule lipoprotein(a) inhibitor, muvalaplin, in high-risk cardiovascular patients with elevated lipoprotein(a) levels.","authors":"Alpo Vuorio, Petri T Kovanen, Frederick Raal","doi":"10.21037/atm-25-40","DOIUrl":"10.21037/atm-25-40","url":null,"abstract":"","PeriodicalId":8216,"journal":{"name":"Annals of translational medicine","volume":"13 2","pages":"11"},"PeriodicalIF":0.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}