The following graduate thesis aims to identify important clinical variables, including injury, treatment and healing characteristics, that serve as prognostic indicators for complications in patients with fractures of the tibial shaft. In particular, the complications of focus in this thesis are surgical site infections and nonunion. The three analytical studies comprising this thesis were derived from large data sets arising from two randomized controlled trials and an observational cohort study. The first chapter (Open Tibial Fractures: Updated Guidelines for Management) is a published literature review that provides an overall introduction to the thesis. It highlights the paucity of high-quality evidence currently available to inform many of the treatment strategies for patients with open fractures of the tibial shaft. The second chapter (Timing of Irrigation & Debridement and Infection Risk in Severe Open Fractures) is a sub-study of all open fracture patients recruited in the International Orthopaedic Multicenter Study (INORMUS) in Fracture Care. The findings of this study suggest that timing delays to irrigation and debridement for patients with open fracture injuries is associated with an increased risk of surgical site infection. The third and fourth chapters evaluate the association between early healing measures and nonunion in patients with tibial fractures. Specifically, chapter three (Exploring the Association of 3-Month Radiographic Union Score for Tibia Fractures (RUST) with Nonunion in Tibial Shaft Fracture Patients) demonstrates that radiographic healing at three months post-operatively is strongly associated with nonunion at one year. Similarly, chapter four (Nonunion in Patients with Tibial Shaft Fractures—Can Early Functional Status Predict Healing?) demonstrates that functional status at three months post-operatively is also correlated to eventual healing. Both of these studies include patients from the randomized controlled trials, SPRINT (Study to Prospectively Evaluate Reamed Intramedullary Nails in Patients with Tibial Fractures) and FLOW (Fluid Lavage of Open Wounds). / Thesis / Master of Science (MSc) / The enclosed thesis work evaluates outcomes in patients with fractures primarily of the tibial shaft. In particular, the comprised studies assess whether certain characteristics, such as injury factors, treatment variables and early healing progression, are associated with adverse outcomes in these patients. One study found that delays in timing to appropriate surgical care for patients with open fractures (open wound at the site of the fracture) leads to greater risk of infection. Furthermore, two studies found that both the level of radiographic healing and functional status of patients at three months from surgery can help predict if the patient will ultimately heal radiographically at one year from injury. The findings of this thesis work should help orthopaedic care providers identify patients at high risk for infections and nonunions, such that these patients can be closely monitored to minimize the risk of such complications.

Background: In an ongoing study conducted at Karolinska Institutet & Karolinska University Hospital, Positron Emission Tomography (PET)/Computed Tomography (CT) scans are performed on patients with tibia fractures and deformations treated with Taylor Spatial Frames (TSFs) in order to monitor their bone remodeling progress. Each patients receive an administration of approximately 2 MBq/kg bodyweight of Na18F associated with PET scans on two sessions, six and twelve weeks after the attachment of the TSF. These PET/CT scans provide information about the progress of the healing bone and can be used to estimate the optimal time point for de-attachment of the TSF. The Standardized Uptake Value (SUV) is used as a measure of the rate of bone remodeling for these patients, however, there is a need for verification of this practice by a method independent of the PET scanner. Furthermore, information regarding the biodistribution of the Na18F throughout the body of these patients and the effects of the TSF on the CT scan X‑rays is required. Additionally, an investigation of alternative methods that have the potential to provide similar information with a lower absorbed dose to the patients is desirable. Materials and methods: Thermoluminescent Dosimeters (TLDs) were attached on the skin at the position of the heart, urinary bladder, femurs, fracture, and the contralateral tibia of twelve patients during the first one hour and five minutes after the administration of the Na18F. Additional TLD measurements were performed during the CT scan of two of these patients. From the PET scan images, SUVs at the fracture site of these patients were collected. An investigation of the possibility of exploiting the “naturally” occurring bone seeking radionuclide Strontium-90 (90Sr) in the human body to gain information about the fracture site was undertaken. Using a 90Sr source, three different detection techniques were evaluated and a practical methodology for in vivo measurements on the tibia fracture patients was developed. As it was concluded that TLD based measurements were the most suitable technique for this purpose, and it was tested on five patients with tibia fractures. Results: From the collected TLD data, it was concluded that for these patients the urinary bladder is the organ receiving the greatest amount of absorbed dose and the organ most affected as the administered activity exceeds 2 MBq/kg. On average, a three times higher surface dose was measured on the tibia fracture compared to the un-fractured tibia. A linear relationship between the surface dose and SUVmax was shown. A strong positive correlation between the activity concentration at the fracture site and the amount of injected activity was found, and it was demonstrated that this also affects the SUVs. For patients who were administered different amounts of Na18F for the two PET scans, maximum activity concentrationwas less affected than mean activity concentration. It was concluded that TSF’s effect on the scatter of the X-rays to organs higher up in the body is negligible. Regarding “naturally” occurring 90Sr in the human body, no higher activity at the fractured tibia compared to the non‑fractured tibia could be found. Conclusions: This project assessed the accumulation of Na18F in the fracture site of patients treated with TSF by a method independent of the PET scanner. The methodology of using SUVs as an indicator for bone remodeling was verified. It was shown that the uptake of Na18F by the fracture site is strongly correlated to the amount of injected activity. The importance of considering the amount of injected activity when evaluating and comparing SUVs was highlighted. In vivo measurements using LiF:Mn TLDs did not indicate any quantifiable higher concentration of 90Sr at the fracture in the tibia bone.