Pub Date : 2024-09-06DOI: 10.1097/JS9.0000000000002077
Xin-Jia Cai, Chao-Ran Peng, Ying-Ying Cui, Long Li, Ming-Wei Huang, He-Yu Zhang, Jian-Yun Zhang, Tie-Jun Li
Background: Loss of chromosome 9p is an important biomarker in the malignant transformation of oral leukoplakia (OLK) to head and neck squamous cell carcinoma (HNSCC), and is associated with the prognosis of HNSCC patients. However, various challenges have prevented 9p loss from being assessed in clinical practice. The objective of this study was to develop a pathomics-based artificial intelligence (AI) model for the rapid and cost-effective prediction of 9p loss (9PLP).
Materials and methods: 333 OLK cases were retrospectively collected with hematoxylin and eosin (H&E)-stained whole slide images and genomic alteration data from multicenter cohorts to develop the genomic alteration prediction AI model. They were divided into a training dataset (n=217), a validation dataset (n=93), and an external testing dataset (n=23). The latest Transformer method and XGBoost algorithm were combined to develop the 9PLP model. The AI model was further applied and validated in two multicenter HNSCC datasets (n=42, n=365, respectively). Moreover, the combination of 9PLP with clinicopathological parameters was used to develop a nomogram model for assessing HNSCC patient prognosis.
Results: 9PLP could predict chromosome 9p loss rapidly and effectively using both OLK and HNSCC images, with the area under the curve achieving 0.890 and 0.825, respectively. Furthermore, the predictive model showed high accuracy in HNSCC patient prognosis assessment (the area under the curve was 0.739 for 1-year prediction, 0.705 for 3-year prediction, and 0.691 for 5-year prediction).
Conclusion: To the best of our knowledge, this study developed the first genomic alteration prediction deep learning model in OLK and HNSCC. This novel AI model could predict 9p loss and assess patient prognosis by identifying pathomics features in H&E-stained images with good performance. In the future, the 9PLP model may potentially contribute to better clinical management of OLK and HNSCC.
{"title":"Identification of genomic alteration and prognosis using pathomics-based artificial intelligence in oral leukoplakia and head and neck squamous cell carcinoma: A multicenter experimental study.","authors":"Xin-Jia Cai, Chao-Ran Peng, Ying-Ying Cui, Long Li, Ming-Wei Huang, He-Yu Zhang, Jian-Yun Zhang, Tie-Jun Li","doi":"10.1097/JS9.0000000000002077","DOIUrl":"https://doi.org/10.1097/JS9.0000000000002077","url":null,"abstract":"<p><strong>Background: </strong>Loss of chromosome 9p is an important biomarker in the malignant transformation of oral leukoplakia (OLK) to head and neck squamous cell carcinoma (HNSCC), and is associated with the prognosis of HNSCC patients. However, various challenges have prevented 9p loss from being assessed in clinical practice. The objective of this study was to develop a pathomics-based artificial intelligence (AI) model for the rapid and cost-effective prediction of 9p loss (9PLP).</p><p><strong>Materials and methods: </strong>333 OLK cases were retrospectively collected with hematoxylin and eosin (H&E)-stained whole slide images and genomic alteration data from multicenter cohorts to develop the genomic alteration prediction AI model. They were divided into a training dataset (n=217), a validation dataset (n=93), and an external testing dataset (n=23). The latest Transformer method and XGBoost algorithm were combined to develop the 9PLP model. The AI model was further applied and validated in two multicenter HNSCC datasets (n=42, n=365, respectively). Moreover, the combination of 9PLP with clinicopathological parameters was used to develop a nomogram model for assessing HNSCC patient prognosis.</p><p><strong>Results: </strong>9PLP could predict chromosome 9p loss rapidly and effectively using both OLK and HNSCC images, with the area under the curve achieving 0.890 and 0.825, respectively. Furthermore, the predictive model showed high accuracy in HNSCC patient prognosis assessment (the area under the curve was 0.739 for 1-year prediction, 0.705 for 3-year prediction, and 0.691 for 5-year prediction).</p><p><strong>Conclusion: </strong>To the best of our knowledge, this study developed the first genomic alteration prediction deep learning model in OLK and HNSCC. This novel AI model could predict 9p loss and assess patient prognosis by identifying pathomics features in H&E-stained images with good performance. In the future, the 9PLP model may potentially contribute to better clinical management of OLK and HNSCC.</p>","PeriodicalId":14401,"journal":{"name":"International journal of surgery","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: The present study aims to explore the roles of infusion time, administration sequence and interval of immunochemotherapy (IO) in predicting overall survival (OS) in patients with locally advanced ESCC.
Methods: This multi-center retrospective study enrolled advanced ESCC who received IO between Nov 2019 and Nov 2021. Patients were divided into groups according to the three classifiers (IO infusion time, administration sequence, and infusion interval), and were further analyzed for the roles of these classifiers in predicting the prognosis of the ESCC patients.
Results: A total of 183 eligible patients with locally advanced ESCC were included in this study. Patients who received ≥ 75% of immunotherapy drug infusions after 12:00 h had better OS compared to those who received < 75% of immunotherapy drug infusions after 12:00 h in the 1:1 propensity score matching analysis (HRadjusted: 0.38, 95% CI: 0.17-0.82; P = 0.013). Cox proportional hazards regression revealed that ESCC patients with shorter infusion interval (< 3.3 h) had better OS (HRadjusted: 0.34, 95% CI: 0.15-0.76; P = 0.008).
Conclusion: For patients with ESCC, the OS is significantly better when immunotherapy was administered after 12:00 h. A shorter infusion interval (< 3.3 hours) on the same-day immunochemotherapy could lead to a better prognosis.
{"title":"Effect of immunochemotherapy infusion timing, sequence, and interval on prognosis of advanced esophageal cancer: A retrospective cohort study.","authors":"Shujie Huang, Zijie Li, Zhen Gao, Sichao Wang, Jiating Sun, Hansheng Wu, Jixian Liu, Patrick Ming-Kuen Tang, Rixin Chen, Guibin Qiao","doi":"10.1097/JS9.0000000000002085","DOIUrl":"https://doi.org/10.1097/JS9.0000000000002085","url":null,"abstract":"<p><strong>Objective: </strong>The present study aims to explore the roles of infusion time, administration sequence and interval of immunochemotherapy (IO) in predicting overall survival (OS) in patients with locally advanced ESCC.</p><p><strong>Methods: </strong>This multi-center retrospective study enrolled advanced ESCC who received IO between Nov 2019 and Nov 2021. Patients were divided into groups according to the three classifiers (IO infusion time, administration sequence, and infusion interval), and were further analyzed for the roles of these classifiers in predicting the prognosis of the ESCC patients.</p><p><strong>Results: </strong>A total of 183 eligible patients with locally advanced ESCC were included in this study. Patients who received ≥ 75% of immunotherapy drug infusions after 12:00 h had better OS compared to those who received < 75% of immunotherapy drug infusions after 12:00 h in the 1:1 propensity score matching analysis (HRadjusted: 0.38, 95% CI: 0.17-0.82; P = 0.013). Cox proportional hazards regression revealed that ESCC patients with shorter infusion interval (< 3.3 h) had better OS (HRadjusted: 0.34, 95% CI: 0.15-0.76; P = 0.008).</p><p><strong>Conclusion: </strong>For patients with ESCC, the OS is significantly better when immunotherapy was administered after 12:00 h. A shorter infusion interval (< 3.3 hours) on the same-day immunochemotherapy could lead to a better prognosis.</p>","PeriodicalId":14401,"journal":{"name":"International journal of surgery","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-06DOI: 10.1097/JS9.0000000000002081
Longping Yao, Rui Chen, Zijian Zheng, Maryam Hatami, Sumeyye Koc, Xu Wang, Yang Bai, Chen Yao, Guohui Lu, Thomas Skutella
Background: Parkinson's disease (PD) is linked with metabolic risk factors including body mass index (BMI), fasting blood glucose (FBG), cholesterol levels, and triglycerides (TG). The extent to which these factors affect motor symptoms, depression, and sleep problems in PD, as well as their role in determining the success of deep brain stimulation (DBS) therapy, is yet to be fully understood.
Methods: This study delved into the effects of metabolic risk factors like BMI, FBG, cholesterol, and TG on the outcomes of DBS in treating PD-related depression and sleep disturbances, across both mouse models and human subjects.
Results: DBS showcased noticeable betterment in depression and sleep perturbations in both PD-afflicted mice and patients. High-sugar-high-fat diet aggravates MPTP-induced depression and sleep disorders in mice. PD-afflicted individuals presenting with depressive and sleep disorders demonstrated elevated metrics of BMI, FBG, blood cholesterol, and TG. Remarkably, these metrics bore considerable adverse influences on the efficiency of DBS in ameliorating depression and sleep issues, yet spared motor symptoms. The favorable impacts of DBS persisted for approximately 6 years, post which a significant decline was noted. Importantly, our translational evidence from both murine controls and patient cohorts indicated that antihyperglycemic and antihyperlipidemic therapies bolstered the efficacy of DBS in mitigating PD-related depression and sleep disturbances, without impinging upon motor functions in patients.
Conclusion: In summary, this research emphasizes that DBS is a powerful treatment option for depression and sleep issues in PD, with its success influenced by metabolic risk factors. It further suggests that incorporating treatments for high blood sugar and cholesterol can enhance the efficacy of DBS in treating depression and sleep disturbances in PD, without impacting motor symptoms, highlighting the importance of metabolic risk management in PD patients receiving DBS.
{"title":"Translational evaluation of metabolic risk factors impacting DBS efficacy for PD-Related sleep and depressive disorders: preclinical, prospective and cohort studies.","authors":"Longping Yao, Rui Chen, Zijian Zheng, Maryam Hatami, Sumeyye Koc, Xu Wang, Yang Bai, Chen Yao, Guohui Lu, Thomas Skutella","doi":"10.1097/JS9.0000000000002081","DOIUrl":"https://doi.org/10.1097/JS9.0000000000002081","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease (PD) is linked with metabolic risk factors including body mass index (BMI), fasting blood glucose (FBG), cholesterol levels, and triglycerides (TG). The extent to which these factors affect motor symptoms, depression, and sleep problems in PD, as well as their role in determining the success of deep brain stimulation (DBS) therapy, is yet to be fully understood.</p><p><strong>Methods: </strong>This study delved into the effects of metabolic risk factors like BMI, FBG, cholesterol, and TG on the outcomes of DBS in treating PD-related depression and sleep disturbances, across both mouse models and human subjects.</p><p><strong>Results: </strong>DBS showcased noticeable betterment in depression and sleep perturbations in both PD-afflicted mice and patients. High-sugar-high-fat diet aggravates MPTP-induced depression and sleep disorders in mice. PD-afflicted individuals presenting with depressive and sleep disorders demonstrated elevated metrics of BMI, FBG, blood cholesterol, and TG. Remarkably, these metrics bore considerable adverse influences on the efficiency of DBS in ameliorating depression and sleep issues, yet spared motor symptoms. The favorable impacts of DBS persisted for approximately 6 years, post which a significant decline was noted. Importantly, our translational evidence from both murine controls and patient cohorts indicated that antihyperglycemic and antihyperlipidemic therapies bolstered the efficacy of DBS in mitigating PD-related depression and sleep disturbances, without impinging upon motor functions in patients.</p><p><strong>Conclusion: </strong>In summary, this research emphasizes that DBS is a powerful treatment option for depression and sleep issues in PD, with its success influenced by metabolic risk factors. It further suggests that incorporating treatments for high blood sugar and cholesterol can enhance the efficacy of DBS in treating depression and sleep disturbances in PD, without impacting motor symptoms, highlighting the importance of metabolic risk management in PD patients receiving DBS.</p>","PeriodicalId":14401,"journal":{"name":"International journal of surgery","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-06DOI: 10.1097/JS9.0000000000001868
Marjorie T Q Hoang, Ye Xin Koh, Rehena Sultana, John C Allen, Dimitrios Moris, Peng Chung Cheow, Alexander Y F Chung, Prema Raj Jeyaraj, Peter O P Mack, London Lucien P J Ooi, Ek Khoon Tan, Jin Yao Teo, Juinn Huar Kam, Fiona N N Moe, Jacelyn S S Chua, Ashley W Y Ng, Jade S Q Goh, Brian K P Goh, Sabino Zani, Pierce K H Chow
Background: Surgical resection is a curative therapy for early-stage hepatocellular carcinoma (HCC) patients meeting the Milan criteria as well as a widely used therapy in intermediate-stage HCC. However, intermediate-stage HCC encompasses a wide spectrum of disease and there is a lack of good predictive models for the long-term clinical outcome of HCC patients currently. Here, we adopt Mazzaferro's Metroticket 2.0 to create a robust survival prediction model for intermediate-stage HCC patients undergoing surgical resection. Our algorithm considers age, AFP levels, ALBI score, and nodule size/number to generate survival estimates in an accessible graph format. Importantly, our model surpasses the American Joint Committee on Cancer staging model and was validated with independent US patient data.
Methods: We conducted a retrospective analysis of OS and RFS in early- and intermediate-stage HCC patients treated with liver resection, including a training cohort in Singapore and a validation cohort in North Carolina, USA.
Results: We recorded 278 deaths (35.0%) and 428 patients (53.9%) in the first 5-years after surgical resection; higher ALBI score, higher lnAFP, more advanced age and higher tumour burden index were identified as significant parameters. The overall predictive capability of our model, with the inclusion of AFP, is reflected with a UNO's C-statistic of 0.655, which is 1.11 times better than the 0.5895 C-statistic of the 8th AJCC TNM Staging model.
Conclusions: Our modified Metroticket model allows for more granular and better-informed prognostication. This will help surgeons and patients make accurate comparisons between the clinical outcomes of surgical resection and other non-surgical treatments.
{"title":"Metroticket approach in a retrospective cohort study to predict overall survival after surgical resection for intermediate stage hepatocellular carcinoma.","authors":"Marjorie T Q Hoang, Ye Xin Koh, Rehena Sultana, John C Allen, Dimitrios Moris, Peng Chung Cheow, Alexander Y F Chung, Prema Raj Jeyaraj, Peter O P Mack, London Lucien P J Ooi, Ek Khoon Tan, Jin Yao Teo, Juinn Huar Kam, Fiona N N Moe, Jacelyn S S Chua, Ashley W Y Ng, Jade S Q Goh, Brian K P Goh, Sabino Zani, Pierce K H Chow","doi":"10.1097/JS9.0000000000001868","DOIUrl":"https://doi.org/10.1097/JS9.0000000000001868","url":null,"abstract":"<p><strong>Background: </strong>Surgical resection is a curative therapy for early-stage hepatocellular carcinoma (HCC) patients meeting the Milan criteria as well as a widely used therapy in intermediate-stage HCC. However, intermediate-stage HCC encompasses a wide spectrum of disease and there is a lack of good predictive models for the long-term clinical outcome of HCC patients currently. Here, we adopt Mazzaferro's Metroticket 2.0 to create a robust survival prediction model for intermediate-stage HCC patients undergoing surgical resection. Our algorithm considers age, AFP levels, ALBI score, and nodule size/number to generate survival estimates in an accessible graph format. Importantly, our model surpasses the American Joint Committee on Cancer staging model and was validated with independent US patient data.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of OS and RFS in early- and intermediate-stage HCC patients treated with liver resection, including a training cohort in Singapore and a validation cohort in North Carolina, USA.</p><p><strong>Results: </strong>We recorded 278 deaths (35.0%) and 428 patients (53.9%) in the first 5-years after surgical resection; higher ALBI score, higher lnAFP, more advanced age and higher tumour burden index were identified as significant parameters. The overall predictive capability of our model, with the inclusion of AFP, is reflected with a UNO's C-statistic of 0.655, which is 1.11 times better than the 0.5895 C-statistic of the 8th AJCC TNM Staging model.</p><p><strong>Conclusions: </strong>Our modified Metroticket model allows for more granular and better-informed prognostication. This will help surgeons and patients make accurate comparisons between the clinical outcomes of surgical resection and other non-surgical treatments.</p>","PeriodicalId":14401,"journal":{"name":"International journal of surgery","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-06DOI: 10.1097/JS9.0000000000002045
L J van Heurn, Jpm Derikx, N Hall, J H Aldrink, M M Bailez, L B Chirdan, S Fumino, A Hesse, T Soyer, S StPeter, J Twisk, T Yang, Lwe van Heurn
Introduction: Sacrococcygeal teratoma (SCT) is a rare congenital tumour. The risk of malignancy and recurrence are not well defined. Previous studies are small and report differing conclusions about the timing of surgery and the duration of follow-up. We studied the risk of malignant transformation and SCT recurrence after surgery to address these gaps.
Methods: This was a global retrospective cohort study. Data of consecutive SCT patients was obtained from 145 institutes in 62 countries. Malignant transformation, defined as malignancy at initial resection, malignant recurrence or death due to malignancy, and its risk factors were analysed.
Results: Of the 3612 included patients, 3407 entered analysis. Risk of malignant transformation of the initial tumour, was 3.3%, 5.1%, 10.1%, and 32.9% at age three months, six months, one year, and two years, respectively. After six years, the censored risk of malignancy (64%) did not further increase. Recurrent SCT was diagnosed in 349 (10·2%) children with 126 (36·1%) malignant recurrences. Risk factors for recurrence were Altman type II (odds ratio (OR): 1·6, 95% confidence interval (CI): 1·2-2·3), Altman type III (OR: 1·6, 95% CI: 1·2-2·3), initial immature histology (OR: 1·9, 95% CI: 1·4-2·6), and initial malignant histology (OR: 4·0, 95% CI: 2·9-5·4).
Conclusion: The risk of malignancy at initial resection in SCT increases with age reaching a plateau at six years of age. Recurrence after resection occurred in 10% of patients and 36% of these were malignant at that time. Altman type II or type III, and immature or malignant histology were associated with recurrence.
{"title":"Malignant transformation and tumour recurrence in sacrococcygeal teratoma: a global, retrospective cohort study.","authors":"L J van Heurn, Jpm Derikx, N Hall, J H Aldrink, M M Bailez, L B Chirdan, S Fumino, A Hesse, T Soyer, S StPeter, J Twisk, T Yang, Lwe van Heurn","doi":"10.1097/JS9.0000000000002045","DOIUrl":"https://doi.org/10.1097/JS9.0000000000002045","url":null,"abstract":"<p><strong>Introduction: </strong>Sacrococcygeal teratoma (SCT) is a rare congenital tumour. The risk of malignancy and recurrence are not well defined. Previous studies are small and report differing conclusions about the timing of surgery and the duration of follow-up. We studied the risk of malignant transformation and SCT recurrence after surgery to address these gaps.</p><p><strong>Methods: </strong>This was a global retrospective cohort study. Data of consecutive SCT patients was obtained from 145 institutes in 62 countries. Malignant transformation, defined as malignancy at initial resection, malignant recurrence or death due to malignancy, and its risk factors were analysed.</p><p><strong>Results: </strong>Of the 3612 included patients, 3407 entered analysis. Risk of malignant transformation of the initial tumour, was 3.3%, 5.1%, 10.1%, and 32.9% at age three months, six months, one year, and two years, respectively. After six years, the censored risk of malignancy (64%) did not further increase. Recurrent SCT was diagnosed in 349 (10·2%) children with 126 (36·1%) malignant recurrences. Risk factors for recurrence were Altman type II (odds ratio (OR): 1·6, 95% confidence interval (CI): 1·2-2·3), Altman type III (OR: 1·6, 95% CI: 1·2-2·3), initial immature histology (OR: 1·9, 95% CI: 1·4-2·6), and initial malignant histology (OR: 4·0, 95% CI: 2·9-5·4).</p><p><strong>Conclusion: </strong>The risk of malignancy at initial resection in SCT increases with age reaching a plateau at six years of age. Recurrence after resection occurred in 10% of patients and 36% of these were malignant at that time. Altman type II or type III, and immature or malignant histology were associated with recurrence.</p><p><strong>Level of evidence: </strong>level III.</p>","PeriodicalId":14401,"journal":{"name":"International journal of surgery","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-06DOI: 10.1097/JS9.0000000000002075
Chunhao Zhou, Guanyu Hu, Yikai Li, Sheng Zheng
Background: Polydatin (POL), a natural stilbenoid, has multiple pharmacological activities. However, its effect on osteoporotic bone defect has not yet been examined. This study was designed to explore the unknown role of POL on osteoporotic bone repair.
Methods: The effect of POL on osteogenesis and angiogenesis were investigated firstly. Then a series of angiogenesis-related assays were carried out to explore the relationship between osteogenesis and angiogenesis of POL, and the underlying mechanism was further explored. Whereafter, ovariectomy-induced osteoporosis rats with bone defect were treated with POL or placebo, the imageological and histological examinations were conducted to assess the effect of POL on osteoporotic bone repair.
Results: The moderate concentrations (1 μM and 10 μM) of POL enhanced osteogenesis of bone marrow mesenchymal stem cells (BMSCs) and elevated the expression of angiogenic-specific markers. Further research found that POL induced human umbilical vein endothelial cells migration and tube formation through the osteogenesis-angiogenesis coupling of BMSCs, and the POL-induced osteogenesis-angiogenesis coupling was reversed after co-cultured with LY294002, Mechanistically, this was conducted via activating PI3K/AKT/GSK-3β/β-catenin pathway. After that, using osteoporotic bone defect rat model, we observed that POL facilitated osteoporotic bone repair through enhancing osteogenesis and CD31hiEMCNhi type H-positive vessels formation via the PI3K/AKT/GSK-3β/β-catenin pathway.
Conclusion: The data above indicated that POL could accelerate osteoporotic bone repair by inducing the osteogenesis-angiogenesis coupling of BMSCs via the PI3K/AKT/GSK-3β/β-catenin pathway, which provided new insight and strategy for osteoporotic bone repair.
背景:多靛酚(POL)是一种天然类芪类化合物,具有多种药理活性。然而,它对骨质疏松性骨缺损的影响尚未得到研究。本研究旨在探索 POL 对骨质疏松性骨修复的未知作用:方法:首先研究 POL 对骨生成和血管生成的影响。方法:首先研究了 POL 对骨生成和血管生成的影响,然后进行了一系列血管生成相关试验,以探讨 POL 的骨生成和血管生成之间的关系,并进一步探索其潜在机制。之后,用 POL 或安慰剂治疗卵巢切除诱导的骨质疏松症大鼠的骨缺损,并进行影像学和组织学检查,以评估 POL 对骨质疏松症骨修复的影响:结果:中等浓度(1 μM和10 μM)的POL增强了骨髓间充质干细胞(BMSCs)的成骨能力,并提高了血管生成特异性标志物的表达。进一步研究发现,POL通过BMSCs的成骨-血管生成耦合诱导人脐静脉内皮细胞迁移和管形成,而与LY294002共培养后,POL诱导的成骨-血管生成耦合被逆转,其机制是通过激活PI3K/AKT/GSK-3β/β-catenin通路进行的。随后,我们利用骨质疏松性骨缺损大鼠模型观察到,POL通过PI3K/AKT/GSK-3β/β-catenin途径促进骨生成和CD31hiEMCNhi H型阳性血管形成,从而促进骨质疏松性骨修复:上述数据表明,POL可通过PI3K/AKT/GSK-3β/β-catenin通路诱导BMSCs的成骨-血管生成耦合,从而加速骨质疏松症骨修复,为骨质疏松症骨修复提供了新的思路和策略。
{"title":"Polydatin accelerates osteoporotic bone repair by inducing the osteogenesis-angiogenesis coupling of bone marrow mesenchymal stem cells via the PI3K/AKT/GSK-3β/β-catenin pathway.","authors":"Chunhao Zhou, Guanyu Hu, Yikai Li, Sheng Zheng","doi":"10.1097/JS9.0000000000002075","DOIUrl":"https://doi.org/10.1097/JS9.0000000000002075","url":null,"abstract":"<p><strong>Background: </strong>Polydatin (POL), a natural stilbenoid, has multiple pharmacological activities. However, its effect on osteoporotic bone defect has not yet been examined. This study was designed to explore the unknown role of POL on osteoporotic bone repair.</p><p><strong>Methods: </strong>The effect of POL on osteogenesis and angiogenesis were investigated firstly. Then a series of angiogenesis-related assays were carried out to explore the relationship between osteogenesis and angiogenesis of POL, and the underlying mechanism was further explored. Whereafter, ovariectomy-induced osteoporosis rats with bone defect were treated with POL or placebo, the imageological and histological examinations were conducted to assess the effect of POL on osteoporotic bone repair.</p><p><strong>Results: </strong>The moderate concentrations (1 μM and 10 μM) of POL enhanced osteogenesis of bone marrow mesenchymal stem cells (BMSCs) and elevated the expression of angiogenic-specific markers. Further research found that POL induced human umbilical vein endothelial cells migration and tube formation through the osteogenesis-angiogenesis coupling of BMSCs, and the POL-induced osteogenesis-angiogenesis coupling was reversed after co-cultured with LY294002, Mechanistically, this was conducted via activating PI3K/AKT/GSK-3β/β-catenin pathway. After that, using osteoporotic bone defect rat model, we observed that POL facilitated osteoporotic bone repair through enhancing osteogenesis and CD31hiEMCNhi type H-positive vessels formation via the PI3K/AKT/GSK-3β/β-catenin pathway.</p><p><strong>Conclusion: </strong>The data above indicated that POL could accelerate osteoporotic bone repair by inducing the osteogenesis-angiogenesis coupling of BMSCs via the PI3K/AKT/GSK-3β/β-catenin pathway, which provided new insight and strategy for osteoporotic bone repair.</p>","PeriodicalId":14401,"journal":{"name":"International journal of surgery","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-05DOI: 10.1097/JS9.0000000000002068
Chien-Hui Wu, Te-Wei Ho, Ching-Hsuan Chen, Kuo-Liong Chien, Yu-Wen Tien
Background: Endoscopic ultrasound-guided aspiration or biopsy allows preoperative confirmation of malignancy but is not necessary for resectable pancreatic cancer. Preoperative biopsy may induce pancreatitis, making surgery difficult and complex. Therefore, we performed a retrospective study to evaluate the association between preoperative endoscopic ultrasound-guided biopsy and surgical outcomes in patients with resectable pancreatic head tumors.
Materials and methods: A prospectively enrolled cohort from a single high-volume pancreatic center was analyzed. Between 2007 and 2019, a total of 518 patients with resectable pancreatic head tumors underwent pancreaticoduodenectomy. This analysis was performed to determine the association of preoperative endoscopic ultrasound-guided biopsy with operating time and major complications.
Results: In 518 patients who received pancreaticoduodenectomy, 164 patients (31.6%) underwent preoperative endoscopic ultrasound-guided biopsy. Endoscopic ultrasound-guided biopsy increased surgical time (46.9 min, confidence interval: 25.1-68.8, P-value <0.05) without increasing complications (odds ratio: 0.53, confidence interval: 0.31-1.29, P-value=0.29).
Conclusion: Preoperative endoscopic ultrasound-guided biopsy for pancreatic head tumors may increase operative time but is not associated with an increased risk of mortality and complications.
{"title":"Preoperative endoscopic ultrasound-guided biopsy for resectable pancreatic head tumors increases operative time but not complications - a single center cohort study.","authors":"Chien-Hui Wu, Te-Wei Ho, Ching-Hsuan Chen, Kuo-Liong Chien, Yu-Wen Tien","doi":"10.1097/JS9.0000000000002068","DOIUrl":"https://doi.org/10.1097/JS9.0000000000002068","url":null,"abstract":"<p><strong>Background: </strong>Endoscopic ultrasound-guided aspiration or biopsy allows preoperative confirmation of malignancy but is not necessary for resectable pancreatic cancer. Preoperative biopsy may induce pancreatitis, making surgery difficult and complex. Therefore, we performed a retrospective study to evaluate the association between preoperative endoscopic ultrasound-guided biopsy and surgical outcomes in patients with resectable pancreatic head tumors.</p><p><strong>Materials and methods: </strong>A prospectively enrolled cohort from a single high-volume pancreatic center was analyzed. Between 2007 and 2019, a total of 518 patients with resectable pancreatic head tumors underwent pancreaticoduodenectomy. This analysis was performed to determine the association of preoperative endoscopic ultrasound-guided biopsy with operating time and major complications.</p><p><strong>Results: </strong>In 518 patients who received pancreaticoduodenectomy, 164 patients (31.6%) underwent preoperative endoscopic ultrasound-guided biopsy. Endoscopic ultrasound-guided biopsy increased surgical time (46.9 min, confidence interval: 25.1-68.8, P-value <0.05) without increasing complications (odds ratio: 0.53, confidence interval: 0.31-1.29, P-value=0.29).</p><p><strong>Conclusion: </strong>Preoperative endoscopic ultrasound-guided biopsy for pancreatic head tumors may increase operative time but is not associated with an increased risk of mortality and complications.</p>","PeriodicalId":14401,"journal":{"name":"International journal of surgery","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-05DOI: 10.1097/JS9.0000000000002074
Ming Ma, Jun Zeng, Mengli Zhu, Hui Li, Tao Lin, Hao Yang, Xin Wei, Turun Song
Background: Human umbilical cord mesenchymal stem cells derived extracellular vesicles (HUMSC-EVs) have drawn much interest in kidney transplantation, mainly because of their renoprotection by alleviating cell injury and stimulating tissue repair. Cellular senescence has been proven to play a dual regulatory role in kidney ischemia-reperfusion injury (IRI), and the regulation of HUMSC-EVs on tubular epithelial cell senescence may be a potential therapeutic target.
Materials and methods: In vitro, the hypoxia-reoxygenation of human kidney-2 cells was used to simulate kidney IRI, and the regulation of HUMSC-EVs on human kidney-2 cells was detected. Transcriptome sequencing of human kidney-2 cells was used to explore the potential regulatory mechanism. In vivo, adult male mice were divided into five groups: control group, IRI group, HUMSC-EVs treatment group, senolytics treatment group (dasatinib + quercetin), and combined treatments group (HUMSC-EVs and senolytics). Kidney function, senescent features of tubular epithelial cells, acute kidney injury, and chronic interstitial fibrosis in mice were detected to explore the renoprotection effects of HUMSC-EVs.
Results: Kidney IRI significantly up-regulated expressions of LaminB1, p53, p21, p16, senescence-associated beta-galactosidase, and apoptosis of tubular epithelial cells. In the mouse kidney IRI model, kidney subcapsular injection of HUMSC-EVs significantly improved kidney function, reducing the senescent features of tubular epithelial cells and alleviating acute kidney injury and chronic interstitial fibrosis. HUMSC-EVs mainly achieved renoprotection by regulating Bax/Bcl-2-dependent apoptosis during acute kidney injury and mostly reduced tubular atrophy and kidney interstitial fibrosis by regulating Ras-pERK-Ets1-p53 pathway-dependent cell senescence. Oral administration of senolytics also alleviated kidney injury induced by IRI, while the combined treatments of HUMSC-EVs and senolytics had better renoprotection effects.
Conclusions: The combination of HUMSC-EVs and senolytics alleviated acute kidney injury and chronic interstitial fibrosis by dynamic regulation of cell senescence and apoptosis, which provides a therapeutic potential strategy for organ preservation and tissue repair in kidney transplantation.
{"title":"Human umbilical cord mesenchymal stem cells derived extracellular vesicles ameliorate kidney ischemia-reperfusion injury by suppression of senescent tubular epithelial cells - Experimental Study.","authors":"Ming Ma, Jun Zeng, Mengli Zhu, Hui Li, Tao Lin, Hao Yang, Xin Wei, Turun Song","doi":"10.1097/JS9.0000000000002074","DOIUrl":"https://doi.org/10.1097/JS9.0000000000002074","url":null,"abstract":"<p><strong>Background: </strong>Human umbilical cord mesenchymal stem cells derived extracellular vesicles (HUMSC-EVs) have drawn much interest in kidney transplantation, mainly because of their renoprotection by alleviating cell injury and stimulating tissue repair. Cellular senescence has been proven to play a dual regulatory role in kidney ischemia-reperfusion injury (IRI), and the regulation of HUMSC-EVs on tubular epithelial cell senescence may be a potential therapeutic target.</p><p><strong>Materials and methods: </strong>In vitro, the hypoxia-reoxygenation of human kidney-2 cells was used to simulate kidney IRI, and the regulation of HUMSC-EVs on human kidney-2 cells was detected. Transcriptome sequencing of human kidney-2 cells was used to explore the potential regulatory mechanism. In vivo, adult male mice were divided into five groups: control group, IRI group, HUMSC-EVs treatment group, senolytics treatment group (dasatinib + quercetin), and combined treatments group (HUMSC-EVs and senolytics). Kidney function, senescent features of tubular epithelial cells, acute kidney injury, and chronic interstitial fibrosis in mice were detected to explore the renoprotection effects of HUMSC-EVs.</p><p><strong>Results: </strong>Kidney IRI significantly up-regulated expressions of LaminB1, p53, p21, p16, senescence-associated beta-galactosidase, and apoptosis of tubular epithelial cells. In the mouse kidney IRI model, kidney subcapsular injection of HUMSC-EVs significantly improved kidney function, reducing the senescent features of tubular epithelial cells and alleviating acute kidney injury and chronic interstitial fibrosis. HUMSC-EVs mainly achieved renoprotection by regulating Bax/Bcl-2-dependent apoptosis during acute kidney injury and mostly reduced tubular atrophy and kidney interstitial fibrosis by regulating Ras-pERK-Ets1-p53 pathway-dependent cell senescence. Oral administration of senolytics also alleviated kidney injury induced by IRI, while the combined treatments of HUMSC-EVs and senolytics had better renoprotection effects.</p><p><strong>Conclusions: </strong>The combination of HUMSC-EVs and senolytics alleviated acute kidney injury and chronic interstitial fibrosis by dynamic regulation of cell senescence and apoptosis, which provides a therapeutic potential strategy for organ preservation and tissue repair in kidney transplantation.</p>","PeriodicalId":14401,"journal":{"name":"International journal of surgery","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-05DOI: 10.1097/JS9.0000000000002067
Jianye Yang, Leilei Qin, Chen Zhao, Hai Wang, Cheng Chen, Tao Zhang, Bo Zhu, Li Wei, Xudong Su, Yujian Li, Ning Hu, Wei Huang
Preoperative diagnosis of periprosthetic joint infection (PJI) is critical to guide treatment options and improve patient outcomes. In this letter, we discuss results from our experiences with a novel nomogram diagnosis model based on serum and synovial fluid indicators for the preoperative diagnosis of PJI. The results showed that the novel nomogram diagnosis model can distinguish PJI from aseptic loosening before the operation. And it is also a useful candidate for the selection of the timing of current secondary revision.
{"title":"Diagnosis of periprosthesis joint infection and selection of replantation timing: A novel nomogram diagnosis model.","authors":"Jianye Yang, Leilei Qin, Chen Zhao, Hai Wang, Cheng Chen, Tao Zhang, Bo Zhu, Li Wei, Xudong Su, Yujian Li, Ning Hu, Wei Huang","doi":"10.1097/JS9.0000000000002067","DOIUrl":"https://doi.org/10.1097/JS9.0000000000002067","url":null,"abstract":"<p><p>Preoperative diagnosis of periprosthetic joint infection (PJI) is critical to guide treatment options and improve patient outcomes. In this letter, we discuss results from our experiences with a novel nomogram diagnosis model based on serum and synovial fluid indicators for the preoperative diagnosis of PJI. The results showed that the novel nomogram diagnosis model can distinguish PJI from aseptic loosening before the operation. And it is also a useful candidate for the selection of the timing of current secondary revision.</p>","PeriodicalId":14401,"journal":{"name":"International journal of surgery","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-05DOI: 10.1097/JS9.0000000000002069
Pei-Hsin Hsiung, Ho-Yin Huang, Wei-Yu Chen, Yur-Ren Kuo, Ying-Chi Lin
Background: Free flap construction enhances quality of life for head and neck cancer (HNC) patients; however, complications, such as thrombosis and hematoma, threaten flap survival. This study aimed to identify factors influencing flap failure, thrombosis, and hematoma.
Methods: A retrospective nested case-control study was conducted on HNC patients who underwent free flap reconstruction at a tertiary medical center between January 2019 and January 2022. All patients received antithrombotic prophylaxis consisting of prostaglandin E1, dextran, aspirin, and dipyridamole. Risk factors were analyzed using multivariate logistic regression.
Results: Among 548 flaps analyzed, flap failure, thrombosis, and hematoma rates were 4.74%, 3.83%, and 9.65%, respectively. Risk factors for flap failure included thrombosis (OR 86.42, 95% CI 15.73-474.89), smoking (OR 49.44, 95% CI 1.28->1000), posteromedial thigh (PMT) flap usage (OR 14.05, 95% CI 2.48-79.54), hematoma (OR 9.68, 95% CI 2.35-39.79), and younger age (OR 0.93, 95% CI 0.87-0.99). Thrombosis risk factors included PMT usage (OR 11.45, 95% CI 2.60-50.38) and anastomosis with the superior thyroid vein (SThV) as the recipient vein after multiple reconstructions (OR 7.91, 95% CI 2.06-30.39). Hematoma risk factors included fibula osteocutaneous flap usage (OR 9.22, 95% CI 2.71-31.42), double-flap usage (OR 8.88, 95% CI 1.80-43.81), liver cirrhosis (OR 6.28, 95% CI 1.44-27.47), and postsurgery hypertension (OR 2.77, 95% CI 1.39-5.50), whereas ipsilateral recurrence (OR 0.14, 95% CI 0.03-0.73) and using the external jugular vein (EJV) as the recipient vein (OR 0.22, 95% CI 0.08-0.61) were protective factors.
Conclusion: Thrombosis poses a greater risk than hematoma for flap failure. Utilization of the PMT flap and the SThV markedly increased the risk of thrombosis and flap failure. These findings highlight the importance of antithrombotic prophylaxis and the selection of flaps and recipient veins in recurrent HNC patients.
背景:游离皮瓣可提高头颈癌(HNC)患者的生活质量,但血栓和血肿等并发症威胁着皮瓣的存活。本研究旨在确定影响皮瓣失败、血栓形成和血肿的因素:方法:对2019年1月至2022年1月期间在一家三级医疗中心接受游离皮瓣重建术的HNC患者进行了一项回顾性巢式病例对照研究。所有患者均接受了抗血栓预防治疗,包括前列腺素 E1、右旋糖酐、阿司匹林和双嘧达莫。使用多变量逻辑回归分析了风险因素:在分析的 548 个皮瓣中,皮瓣失败率、血栓形成率和血肿形成率分别为 4.74%、3.83% 和 9.65%。皮瓣失败的风险因素包括血栓形成(OR 86.42,95% CI 15.73-474.89)、吸烟(OR 49.44,95% CI 1.28->1000)、使用大腿后内侧(PMT)皮瓣(OR 14.05,95% CI 2.48-79.54)、血肿(OR 9.68,95% CI 2.35-39.79)和年龄较小(OR 0.93,95% CI 0.87-0.99)。血栓风险因素包括使用 PMT(OR 11.45,95% CI 2.60-50.38)和多次重建后以甲状腺上静脉(STHV)作为受体静脉进行吻合(OR 7.91,95% CI 2.06-30.39)。血肿风险因素包括使用腓骨骨皮瓣(OR 9.22,95% CI 2.71-31.42)、使用双瓣(OR 8.88,95% CI 1.80-43.81)、肝硬化(OR 6.28,95% CI 1.44-27.47)和术后高血压(OR 2.77,95% CI 1.39-5.50),而同侧复发(OR 0.14,95% CI 0.03-0.73)和使用颈外静脉(EJV)作为受体静脉(OR 0.22,95% CI 0.08-0.61)是保护因素:结论:与血肿相比,血栓形成对皮瓣失败的风险更大。结论:血栓形成比血肿更容易导致皮瓣失败。使用PMT皮瓣和SThV明显增加了血栓形成和皮瓣失败的风险。这些发现强调了抗血栓预防以及选择皮瓣和受体静脉对复发性 HNC 患者的重要性。
{"title":"Cumulative risk factors for flap failure, thrombosis, and hematoma in free flap reconstruction for head and neck cancer: a retrospective nested case-control study.","authors":"Pei-Hsin Hsiung, Ho-Yin Huang, Wei-Yu Chen, Yur-Ren Kuo, Ying-Chi Lin","doi":"10.1097/JS9.0000000000002069","DOIUrl":"https://doi.org/10.1097/JS9.0000000000002069","url":null,"abstract":"<p><strong>Background: </strong>Free flap construction enhances quality of life for head and neck cancer (HNC) patients; however, complications, such as thrombosis and hematoma, threaten flap survival. This study aimed to identify factors influencing flap failure, thrombosis, and hematoma.</p><p><strong>Methods: </strong>A retrospective nested case-control study was conducted on HNC patients who underwent free flap reconstruction at a tertiary medical center between January 2019 and January 2022. All patients received antithrombotic prophylaxis consisting of prostaglandin E1, dextran, aspirin, and dipyridamole. Risk factors were analyzed using multivariate logistic regression.</p><p><strong>Results: </strong>Among 548 flaps analyzed, flap failure, thrombosis, and hematoma rates were 4.74%, 3.83%, and 9.65%, respectively. Risk factors for flap failure included thrombosis (OR 86.42, 95% CI 15.73-474.89), smoking (OR 49.44, 95% CI 1.28->1000), posteromedial thigh (PMT) flap usage (OR 14.05, 95% CI 2.48-79.54), hematoma (OR 9.68, 95% CI 2.35-39.79), and younger age (OR 0.93, 95% CI 0.87-0.99). Thrombosis risk factors included PMT usage (OR 11.45, 95% CI 2.60-50.38) and anastomosis with the superior thyroid vein (SThV) as the recipient vein after multiple reconstructions (OR 7.91, 95% CI 2.06-30.39). Hematoma risk factors included fibula osteocutaneous flap usage (OR 9.22, 95% CI 2.71-31.42), double-flap usage (OR 8.88, 95% CI 1.80-43.81), liver cirrhosis (OR 6.28, 95% CI 1.44-27.47), and postsurgery hypertension (OR 2.77, 95% CI 1.39-5.50), whereas ipsilateral recurrence (OR 0.14, 95% CI 0.03-0.73) and using the external jugular vein (EJV) as the recipient vein (OR 0.22, 95% CI 0.08-0.61) were protective factors.</p><p><strong>Conclusion: </strong>Thrombosis poses a greater risk than hematoma for flap failure. Utilization of the PMT flap and the SThV markedly increased the risk of thrombosis and flap failure. These findings highlight the importance of antithrombotic prophylaxis and the selection of flaps and recipient veins in recurrent HNC patients.</p>","PeriodicalId":14401,"journal":{"name":"International journal of surgery","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}