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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. 利用基于病理组学的人工智能识别口腔白斑病和头颈部鳞状细胞癌的基因组改变和预后:一项多中心实验研究。
IF 12.5 2区 医学 Q1 SURGERY Pub Date : 2024-09-06 DOI: 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.

背景:9p 染色体缺失是口腔白斑(OLK)恶变为头颈部鳞状细胞癌(HNSCC)的重要生物标志物,与 HNSCC 患者的预后有关。然而,各种挑战阻碍了 9p 缺失在临床实践中的评估。本研究旨在开发一种基于病理组学的人工智能(AI)模型,用于快速、经济地预测9p缺失(9PLP)。材料与方法:回顾性收集了333例OLK病例的苏木精和伊红(H&E)染色的全切片图像以及多中心队列的基因组改变数据,以开发基因组改变预测AI模型。这些数据被分为训练数据集(n=217)、验证数据集(n=93)和外部测试数据集(n=23)。结合最新的 Transformer 方法和 XGBoost 算法,建立了 9PLP 模型。人工智能模型在两个多中心 HNSCC 数据集(分别为 n=42、n=365)中得到了进一步应用和验证。此外,还将 9PLP 与临床病理参数相结合,建立了评估 HNSCC 患者预后的提名图模型:结果:9PLP能利用OLK和HNSCC图像快速有效地预测9p染色体缺失,曲线下面积分别达到0.890和0.825。此外,该预测模型在 HNSCC 患者预后评估中表现出较高的准确性(1 年预测的曲线下面积为 0.739,3 年预测的曲线下面积为 0.705,5 年预测的曲线下面积为 0.691):据我们所知,本研究开发了首个针对 OLK 和 HNSCC 的基因组改变预测深度学习模型。这种新型人工智能模型可以预测 9p 缺失,并通过识别 H&E 染色图像中的病理组学特征来评估患者的预后,效果良好。未来,9PLP模型可能有助于更好地临床管理OLK和HNSCC。
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引用次数: 0
Effect of immunochemotherapy infusion timing, sequence, and interval on prognosis of advanced esophageal cancer: A retrospective cohort study. 免疫化疗输注时间、顺序和间隔对晚期食管癌预后的影响:一项回顾性队列研究。
IF 12.5 2区 医学 Q1 SURGERY Pub Date : 2024-09-06 DOI: 10.1097/JS9.0000000000002085
Shujie Huang, Zijie Li, Zhen Gao, Sichao Wang, Jiating Sun, Hansheng Wu, Jixian Liu, Patrick Ming-Kuen Tang, Rixin Chen, Guibin Qiao

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.

目的:本研究旨在探讨免疫化疗(IO)的输注时间、给药顺序和间隔在预测局部晚期 ESCC 患者总生存期(OS)中的作用:本研究旨在探讨免疫化疗(IO)的输注时间、给药顺序和间隔在预测局部晚期ESCC患者总生存期(OS)中的作用:这项多中心回顾性研究纳入了2019年11月至2021年11月期间接受IO治疗的晚期ESCC患者。根据三个分类指标(IO输注时间、给药顺序和输注间隔)将患者分为几组,并进一步分析这些分类指标在预测ESCC患者预后中的作用:本研究共纳入了183名符合条件的局部晚期ESCC患者。在1:1倾向评分匹配分析中,12:00后接受免疫治疗药物输注≥75%的患者的OS优于12:00后接受免疫治疗药物输注<75%的患者(HR调整后:0.38,95% CI:0.17-0.82;P = 0.013)。Cox比例危险回归显示,输液间隔较短(< 3.3 h)的ESCC患者的OS更好(HR调整后:0.34,95% CI:0.15-0.76;P = 0.008):对于ESCC患者,12:00后进行免疫治疗的患者的OS明显更好。
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引用次数: 0
Translational evaluation of metabolic risk factors impacting DBS efficacy for PD-Related sleep and depressive disorders: preclinical, prospective and cohort studies. 影响 DBS 对与帕金森病相关的睡眠和抑郁障碍疗效的代谢风险因素的转化评估:临床前、前瞻性和队列研究。
IF 12.5 2区 医学 Q1 SURGERY Pub Date : 2024-09-06 DOI: 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.

背景:帕金森病(PD)与代谢风险因素有关,包括体重指数(BMI)、空腹血糖(FBG)、胆固醇水平和甘油三酯(TG)。这些因素对帕金森病患者的运动症状、抑郁和睡眠问题有多大影响,以及它们在决定脑深部刺激(DBS)疗法成功与否方面的作用,目前尚不完全清楚:本研究通过小鼠模型和人类受试者,深入研究了BMI、FBG、胆固醇和TG等代谢风险因素对DBS治疗PD相关抑郁和睡眠障碍效果的影响:结果:DBS明显改善了帕金森病小鼠和患者的抑郁和睡眠障碍。高糖高脂饮食会加重 MPTP 诱导的小鼠抑郁和睡眠障碍。伴有抑郁和睡眠障碍的帕金森病患者的体重指数(BMI)、血脂、血胆固醇和总胆固醇指标都有所升高。值得注意的是,这些指标对 DBS 改善抑郁和睡眠问题的效率有相当大的不利影响,但对运动症状却没有影响。DBS 的有利影响持续了约 6 年,之后出现了显著下降。重要的是,我们从小鼠对照组和患者队列中获得的转化证据表明,降血糖和降血脂疗法增强了DBS在减轻与帕金森病相关的抑郁和睡眠障碍方面的疗效,而不会影响患者的运动功能:总之,这项研究强调,DBS 是治疗帕金森病抑郁和睡眠问题的有效方法,其成功与否受代谢风险因素的影响。研究进一步表明,结合高血糖和高胆固醇治疗可提高 DBS 治疗帕金森病抑郁和睡眠障碍的疗效,同时不会影响患者的运动症状。
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引用次数: 0
Metroticket approach in a retrospective cohort study to predict overall survival after surgical resection for intermediate stage hepatocellular carcinoma. 在一项回顾性队列研究中采用 Metroticket 方法预测中期肝细胞癌手术切除后的总生存率。
IF 12.5 2区 医学 Q1 SURGERY Pub Date : 2024-09-06 DOI: 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.

背景:对于符合米兰标准的早期肝细胞癌(HCC)患者来说,手术切除是一种根治性疗法,也是一种广泛应用于中期 HCC 的疗法。然而,中晚期 HCC 的病变范围很广,目前还缺乏对 HCC 患者长期临床预后的良好预测模型。在此,我们采用 Mazzaferro 的 Metroticket 2.0 为接受手术切除的中晚期 HCC 患者创建了一个稳健的生存预测模型。我们的算法考虑了年龄、甲胎蛋白水平、ALBI 评分和结节大小/数量,以易于理解的图表格式生成生存率估计值。重要的是,我们的模型超越了美国癌症联合委员会的分期模型,并通过独立的美国患者数据进行了验证:我们对接受肝切除术治疗的早期和中期 HCC 患者的 OS 和 RFS 进行了回顾性分析,包括新加坡的训练队列和美国北卡罗来纳州的验证队列:我们记录了278例死亡病例(35.0%)和428例患者(53.9%)在手术切除后头5年的生存期;较高的ALBI评分、较高的lnAFP、较高的年龄和较高的肿瘤负荷指数被确定为重要参数。加入 AFP 后,我们模型的整体预测能力体现在 UNO's C 统计量为 0.655,是第 8 版 AJCC TNM 分期模型 C 统计量 0.5895 的 1.11 倍:我们改进后的Metroticket模型可以提供更精细、更有依据的预后判断。这将有助于外科医生和患者准确比较手术切除和其他非手术治疗的临床结果。
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引用次数: 0
Malignant transformation and tumour recurrence in sacrococcygeal teratoma: a global, retrospective cohort study. 骶尾部畸胎瘤的恶性转化和肿瘤复发:一项全球性回顾性队列研究。
IF 12.5 2区 医学 Q1 SURGERY Pub Date : 2024-09-06 DOI: 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.

Level of evidence: level III.

简介:骶尾部畸胎瘤(SCT)是一种罕见的先天性肿瘤:骶尾部畸胎瘤(SCT)是一种罕见的先天性肿瘤。恶性肿瘤和复发的风险尚不明确。以往的研究规模较小,对手术时机和随访时间的结论也不尽相同。为了弥补这些不足,我们研究了手术后恶性转化和SCT复发的风险:这是一项全球性的回顾性队列研究。我们从 62 个国家的 145 家机构获得了连续 SCT 患者的数据。研究分析了恶性转化(定义为初次切除时的恶性肿瘤、恶性肿瘤复发或因恶性肿瘤死亡)及其风险因素:结果:在纳入的 3612 例患者中,有 3407 例进入分析。3个月、6个月、1年和2岁时,初始肿瘤恶性转化的风险分别为3.3%、5.1%、10.1%和32.9%。六年后,恶性肿瘤的删减风险(64%)没有进一步增加。349例(10-2%)患儿被诊断为复发性SCT,其中126例(36-1%)为恶性复发。复发的风险因素为Altman II型(几率比(OR):1-6,95%置信区间(CI):1-2-2-3)、Altman III型(OR:1-6,95% CI:1-2-2-3)、初始不成熟组织学(OR:1-9,95% CI:1-4-2-6)和初始恶性组织学(OR:4-0,95% CI:2-9-5-4):结论:SCT最初切除时发生恶性肿瘤的风险随着年龄的增长而增加,到6岁时达到高峰。10%的患者在切除术后复发,其中36%当时为恶性。阿尔特曼II型或III型、组织学不成熟或恶性与复发有关。
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引用次数: 0
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. 多肽通过PI3K/AKT/GSK-3β/β-catenin途径诱导骨髓间充质干细胞的成骨-血管生成耦合,从而加速骨质疏松性骨修复。
IF 12.5 2区 医学 Q1 SURGERY Pub Date : 2024-09-06 DOI: 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。
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引用次数: 0
Preoperative endoscopic ultrasound-guided biopsy for resectable pancreatic head tumors increases operative time but not complications - a single center cohort study. 对可切除的胰头肿瘤进行术前内镜超声引导活检会延长手术时间,但不会增加并发症--一项单中心队列研究。
IF 12.5 2区 医学 Q1 SURGERY Pub Date : 2024-09-05 DOI: 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.

背景:内镜超声引导下抽吸或活检可在术前确认恶性肿瘤,但对于可切除的胰腺癌来说并非必要。术前活检可能会诱发胰腺炎,使手术变得困难和复杂。因此,我们进行了一项回顾性研究,评估可切除胰头肿瘤患者术前内镜超声引导活检与手术结果之间的关联:分析了来自一个高容量胰腺中心的前瞻性入组患者。2007年至2019年期间,共有518名可切除胰头肿瘤患者接受了胰十二指肠切除术。该分析旨在确定术前内镜超声引导活检与手术时间和主要并发症的关系:结果:在518名接受胰十二指肠切除术的患者中,有164名患者(31.6%)在术前接受了内镜超声引导下活检。内镜超声引导下活检增加了手术时间(46.9 分钟,置信区间:25.1-68.8,P 值 结论:胰头肿瘤术前内镜超声引导下活检可能会增加手术时间,但与死亡率和并发症风险的增加无关。
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引用次数: 0
Human umbilical cord mesenchymal stem cells derived extracellular vesicles ameliorate kidney ischemia-reperfusion injury by suppression of senescent tubular epithelial cells - Experimental Study. 通过抑制衰老的肾小管上皮细胞改善肾缺血再灌注损伤--实验研究。
IF 12.5 2区 医学 Q1 SURGERY Pub Date : 2024-09-05 DOI: 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.

背景:人脐带间充质干细胞衍生的细胞外囊泡(HUMSC-EVs)在肾移植中备受关注,这主要是因为HUMSC-EVs具有减轻细胞损伤和促进组织修复的肾脏保护作用。细胞衰老已被证实在肾脏缺血再灌注损伤(IRI)中起着双重调控作用,HUMSC-EVs对肾小管上皮细胞衰老的调控可能是一个潜在的治疗靶点:体外模拟肾脏缺血缺氧损伤(IRI),检测HUMSC-EVs对肾小管上皮细胞衰老的调控。通过对人肾-2细胞的转录组测序来探索潜在的调控机制。在体内,成年雄性小鼠被分为五组:对照组、IRI组、HUMSC-EVs治疗组、衰老素治疗组(达沙替尼+槲皮素)和联合治疗组(HUMSC-EVs和衰老素)。通过检测小鼠肾功能、肾小管上皮细胞衰老特征、急性肾损伤和慢性肾间质纤维化,探讨HUMSC-EVs的肾保护作用:结果:肾脏IRI能明显上调LaminB1、p53、p21、p16、衰老相关β-半乳糖苷酶的表达,以及肾小管上皮细胞的凋亡。在小鼠肾脏IRI模型中,肾脏囊下注射HUMSC-EVs能显著改善肾功能,减少肾小管上皮细胞的衰老特征,缓解急性肾损伤和慢性肾间质纤维化。HUMSC-EVs主要通过调节急性肾损伤时Bax/Bcl-2依赖性细胞凋亡实现肾保护,并通过调节Ras-pERK-Ets1-p53通路依赖性细胞衰老减少肾小管萎缩和肾间质纤维化。口服解毒剂也能缓解IRI引起的肾损伤,而HUMSC-EVs和解毒剂联合治疗具有更好的肾保护效果:结论:HUMSC-EVs和抗衰老药物联合使用可通过动态调节细胞衰老和凋亡缓解急性肾损伤和慢性肾间质纤维化,为肾移植中的器官保护和组织修复提供了一种潜在的治疗策略。
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引用次数: 0
Diagnosis of periprosthesis joint infection and selection of replantation timing: A novel nomogram diagnosis model. 假体周围关节感染的诊断和再植时机的选择:新型提名图诊断模型。
IF 12.5 2区 医学 Q1 SURGERY Pub Date : 2024-09-05 DOI: 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.

假体周围关节感染(PJI)的术前诊断对于指导治疗方案和改善患者预后至关重要。在这封信中,我们讨论了基于血清和滑液指标的新型提名图诊断模型用于术前诊断 PJI 的经验结果。结果表明,新型提名图诊断模型可以在术前将 PJI 与无菌性松动区分开来。同时,它也是选择当前二次翻修时机的有用候选指标。
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引用次数: 0
Cumulative risk factors for flap failure, thrombosis, and hematoma in free flap reconstruction for head and neck cancer: a retrospective nested case-control study. 头颈癌游离皮瓣重建术中皮瓣失败、血栓形成和血肿的累积风险因素:一项回顾性巢式病例对照研究。
IF 12.5 2区 医学 Q1 SURGERY Pub Date : 2024-09-05 DOI: 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。
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引用次数: 0
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International journal of surgery
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