Effect of Immune-Enhancing Nutrition on Radical Cystectomy Outcomes- MERIT extension

项目摘要/摘要 接受手术治疗膀胱癌的患者经历了持续的并发症 做手术。对感染抵抗力较低和肌肉萎缩是手术的常见并发症。 根治性膀胱切除术不仅分解代谢严重，而且并发症发生率最高。 在所有的泌尿外科肿瘤手术中。改善免疫功能，促进愈合，减少 感染将为膀胱癌带来显著的好处。该项目的总体目标是减少后 提高对晚期膀胱癌手术并发症的认识 专门化免疫营养如何调节免疫系统以减少感染和骨骼肌 浪费。本项目的目标是评估在RC之前和之后SIM摄入的有效性 手术与热量和氮匹配的ONS相比，可以减少术后并发症。这个 中心假设是SIM将通过抑制血管扩张来减少术后并发症 来自RC手术的MDSCs，保存肌肉，减少感染。这一假说已经被提出。 根据申请者的实验室和实践产生的初步数据。理由是 手术诱导称为髓系抑制细胞的未成熟免疫细胞的扩张，这种细胞 降低对感染的抵抗力，可能会导致肌肉萎缩。SIM卡的引入抑制了扩张 这些细胞，降低感染率，并似乎保护整体并发症和肌肉 浪费。在强劲的初步数据的指导下，这一假设将在三个具体目标上进行检验：1) 比较服用SIM和ONS对RC术后并发症的影响 手术；2)确定与ONS相比，服用SIM对感染和骨骼肌的影响 RC手术造成的浪费；3)评估SIM与ONS在抑制方面的影响 MDSCs，减少炎症，调节免疫环境，营养代谢，或 微生物组。该项目意义重大，因为目前还没有已知的预防感染和 RC手术后肌肉萎缩。这一创新的方法可以改变临床实践，以减少 手术并发症，从而减轻膀胱癌手术负担。

PROJECT SUMMARY/ABSTRACT Patients undergoing surgery to treat their bladder cancer experience persisting complications from their surgery. A lower resistance to infection and muscle wasting are common complications from the surgery. The radical cystectomy operation is not only extremely catabolic, but fraught with the highest complication rate of all the urologic oncology surgeries performed. Improve immune function, enhanced healing and reduced infections would offer significant benefit to bladder cancer. The overall goal of this project is to reduce post- operative complications from the surgical treatment of advanced bladder cancer and to better understand how specialized immunonutrition modulates the immune system to reduce infections and skeletal muscle wasting. The objective of this project is to assess the effectiveness of SIM intake before and after RC surgery compared to a calorie- and nitrogen-matched ONS to reduce post-operative complications. The central hypothesis is that SIM will reduce post-operative complications by restraining the expansion of MDSCs from RC surgery, preserving muscle, and reducing infections. This hypothesis has been formulated on the basis of preliminary data produced in the applicants’ laboratories and practice. The rationale is that surgery induces the expansion of immature immune cells called myeloid-derived suppressor cells, which lower the resistance to infection and may contribute to muscle wasting. SIM intake restrains the expansion of these cells, reduces infection rates, and appears to protect against overall complications and muscle wasting. Guided by strong preliminary data, the hypothesis will be tested in three specific aims: 1) To determine the impact of consuming SIM compared to ONS on post-operative complications from RC surgery; 2) To determine the impact of consuming SIM compared to ONS on infections and skeletal muscle wasting from RC surgery; 3) To evaluate the impact of consuming SIM compared to ONS for restraining MDSCs, decreasing inflammation, and modulating the immune landscape, nutrient metabolism, or the microbiome. The project is significant because there is currently no known means to prevent infections and muscle-wasting after RC surgery. This innovative approach could transform clinical practice to reduce post- operative complications, thereby diminishing the burden of bladder cancer surgery.