Differentiation of aseptic and septic nonunion using molecular biological, histopathological and laboratory criteria

Status:

ongoing

Aims:

The treatment of aseptic and septic nonunion is based on different principles. An early, at best, preoperative determination of nonunion genesis is an important step in therapy optimization, especially regarding economic aspects. In addition, microbial diagnostics alone often fail to detect germs despite the occurrence of typical clinical signs of infection. This results in a continued delay in therapeutic approach due to further steps necessary in order to confirm diagnosis.

Therefore, the aim of this study is to develop additional (pre-) operative diagnostic criteria for the improved differentiation of aseptic and septic nonunion using molecular biological, histopathological and laboratory methods, using microbiological diagnostics as the gold standard. For this purpose, preoperative laboratory and molecular biological findings of peripheral blood samples were analyzed in combination with the microbiological, histological, and molecular biological findings of intraoperative tissue samples with regard to the cause of nonunion. In future work, threshold values and a classification system based on these results should be developed for the appropriate assignment of aseptic or septic nonunion.

Activities/Methods:

This multicenter study will include 90 patients who received surgical revision for a nonunion developed after a femoral or tibial shaft fracture and 30 patients who demonstrated regular bone healing after a femoral or tibial shaft fracture and need elective removal of osteosynthesis material. Subsequently, peripheral blood and tissue samples at the nonunion zone will be collected during surgery.

Afterwards, in addition to the determination of routine laboratory parameters such as C-reactive protein and white blood cell count, microbiological processing of the tissue samples and extracted osteosynthesis material will be performed. Sonication, aerobic and anaerobic long-term incubation, antibiotic resistance determination, and polymerase chain reaction for germ identification, among other things, are used for this purpose.

Additional tissue samples will be examined with regard to morphological differentiation between aseptic and septic nonunion using histological methods.

For the molecular biological portion of this research project, the obtained blood and tissue samples will be analyzed for the expression of inflammatory and counter-regulatory cytokines (e.g. IFNα, TNFα, IL-1, IL-2) and the presence of antimicrobial peptides (e.g. HBD-2, HBD-3).

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