Implant-related Infections in Patients With Skeletal Sarcomas
试验速览
- 阶段
- 不适用
- 状态
- Enrolling By Invitation
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Difference in virulence properties in causative microbes in the two groups of PJI
研究概览
简要总结
The aim of this observational study is to gain knowledge on the microbial and immunological factors behind implant-related infections in patients with skeletal sarcoma.
The main research question the project aims to answer is:
• Are immunological factors more important than microbial factors in peri-prosthetic joint infections in orthopaedic oncology patients?
Patients with skeletal sarcoma planned for primary surgery (tumour resection and replacement with a megaprosthesis) will be sampled intraoperatively to obtain a cross-section bone tissue slice at the resection margin, three soft tissue biopsies and joint fluid (if possible). Patients who develop a peri-prosthetic joint infection after their primary surgery will be sampled in a similar manner during revision surgery.
An additional group of patients with periprosthetic joint infection of a hip or knee prosthesis due to osteoarthritis will be sampled during their revision surgery (bone biopsies, soft tissue biopsies and joint fluid, if possible).
Blood samples will be taken from all patients pre-operatively for extensive biochemical and cellular analyses.
Researchers will compare periprosthetic tissues before and after infection. Further, periprosthetic infected tissues in patients treated for skeletal sarcoma will be compared to periprosthetic infected tissues in patientens treated for osteoarthritis. This will be done to attempt to identify host and microbial mechanisms responsible for the increased infection rate in patients with a megaprosthesis due to skeletal sarcoma (infection incidence rate up to 30%) compared to patients with a hip or knee prosthesis due to osteoarthritis (infection incidence rate 1-2%).
详细描述
In orthopaedic oncology, the risk and consequences of orthopaedic device related infections (ODRIs) are heightened as the patients often have compromised immune responses due to underlying disease, chemotherapy or radiation. The implants used may be weight-bearing to the extent that they are impossible to remove or exchange in case of infection, and thereby, in worst case, resulting in amputation or death. Compared to the 1-2% incidence of PJI in a non-oncological population with a total hip- or knee prosthesis, patients with a megaprosthesis due to skeletal sarcoma have an infection incidence of 3-25%. Patient-related factors, extensive and repeated surgery and large reconstructive implants likely account for the increased incidence.
To our knowledge no study has evaluated the role of microbiological factors such as the biofilm production and susceptibility in this population. Further, deficient immunological factors in these patients, such as defect neutrophil migration, cytokine expression and phagocyte respiratory burst, involved in the killing of microbes, may provide an environment favouring more virulent phenotypes. Fundamental knowledge on the role of biofilm in this population could add to the improvement in treatment planning and outcome.
Distinguishing causative pathogens from contaminants may be challenging, especially in polymicrobial infections. The addition of metagenomic diagnostics, still sparsely used in clinical practice, may improve sensitivities, but predictive accuracy is still an issue. Comparing the results of conventional microbiological culturing with metagenomic sequencing would be of interest to determine the accuracy of current diagnostic methods.
The present study is an exploratory project addressing the multifactorial nature of PJI focusing on microbial phenotype in patients with skeletal sarcoma. The role of host, microbe and implant factors will be investigated using a set of different methods and compared to cases och PJI in patients will a conventional hip- or knee prosthesis.
Pre-operative blood samples will be taken and samples of peri-prosthetic soft tissue, bone and joint fluid will be collected intra-operatively. Patients will be sampled during their primary operation with a megaprosthesis due to skeletal sarcoma and in case of postoperative PJI, they will be sampled in the same manner during their revision surgery. Patients undergoing a reoperation due to PJI in a conventional total hip- or knee prosthesis will also be sampled with blood, bone, soft tissue and joint fluid intraoperatively.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients diagnosed with skeletal sarcoma planned for primary surgery with resection of tumour and replacement with a megaprosthesis.
- •Patients operated with a megaprosthesis due to skeletal sarcoma who develop a peri-prosthetic joint infection (PJI).
- •Patients diagnosed with PJI after total hip or knee replacement due to osteoarthritis.
排除标准
- •None in the group of patients with skeletal sarcoma.
- •Patients in the PJI group who have a total hip or knee replacement are excluded if they use immunomodulary medication or have a immunodeficiency.
结局指标
主要结局
Difference in virulence properties in causative microbes in the two groups of PJI
时间窗: Sampling will occur intraoperatively, bacteria will be frozen, no time frame neccessary
A descriptive analysis of genotype will be conducted
次要结局
- Differences in periprosthetic tissues in the two PJI groups(Sampling will occur intraoperatively, tissues will be preserved, no time frame neccessary)