Expression of VEGF in Peripheral Serum Is a Possible Prognostic Factor in Bone-Regeneration via Masquelet-Technique-A Pilot Study.

Two-step Masquelet-technique established a new procedure in the treatment of osseous defects, addressing prerequisites postulated by the "diamond concept". Increase in blood perfusion and growth factors are enhanced by the "Masquelet-membrane". To describe this, we measured serum levels of Vascular Endothelial Growth Factor (VEGF) of patients with atrophic non-unions of long bones undergoing Masquelet-technique. From over 500 non-union patients undergoing Masquelet-technique with prospective follow-up we randomly selected 30 patients. 23 were included, 7 lost to follow-up or excluded because of incomplete data. Serum was drawn at specified intervals before and after surgery. Patients were followed for at least 6 months after step 2. Classification into both groups was performed according to radiological results and clinical outcome 6 months after step 2. Concentration of VEGF in patients' serum was performed via ELISA. 14 achieved osseous consolidation (responder group), 9 cases did not (non-responder). Responders showed a significant increase of serum-VEGF in the first and second week when compared to the preoperative values of step 1. Non-responders showed a significant increase of VEGF in the second week after Steps 1 and 2. Comparison of groups showed significantly higher increase of serum-VEGF week2 after step 1 and preoperative to step 2 for responders. Results show one possibility of illustrating therapeutic progress by monitoring growth factors and possibly allowing prognostic conclusions thereof. This might lead to a more targeted treatment protocol.

Complications and imaging artifacts related to MRI in patients with intramedullary osteosynthesis after proximal femur fracture.

BACKGROUND: Fractures of the proximal femur is one of the most frequent human injuries, and most of the patients are treated with osteosynthesis, such as intramedullary nails. These patients often require magnetic resonance imaging (MRI) scans in their further lives due to various reasons. This raises the question of whether complications with implanted osteosynthesis material such as implant loosening, burning, dislocation, or other complications are to be expected or whether an MRI examination is even suitable with regard to imaging artifacts. METHODS: The aim of this retrospective study was to investigate the rate and type of complications after MRI examinations in patients with inserted intramedullary osteosynthesis device. Furthermore, artifacts in MRI caused by this device were assessed. RESULTS: MRI scans of the head (20 of 62), spine (20 of 62), pelvis (10 of 62), and lower extremity (6/62) were performed. Three of the 62 patients received an MRI of the abdomen, and 2 of the 62 patients received an MRI of the thorax and the upper extremity. Of the 62 patients, noneexperienced complications during the immediate examination. Similarly, none of the patients showed early complications within the first 2 weeks after MRI. In our long-term follow-up examination, no long-term complication after MRI was observed in the recorded 15 patients. Artifacts were found in 14 patients: in MRI scans of the pelvis (10/10), of the abdomen (2/3), and of the lower extremity (2/6). CONCLUSION: There were no complications during the MRI scan, in the first 2 weeks after MRI, or in the recorded long-term results. MRI with an enclosed intramedullary nail provided good image quality unless the immediate implant site was imaged. MRI diagnosis is thus possible in patients with an inserted intramedullary nail. The inserted intramedullary nail should therefore not be an exclusion criterion when sectional imaging with MRI is required.

Safety study: is there a pathologic IGF-1, PDGF and TGF-ß cytokine expression caused by adjunct BMP-7 in tibial and femoral non-union therapy?

BACKGROUND: In this prospective safety study, we investigated if the characteristic cytokine expression during bone regeneration is manipulated by the local application of bone morphogenetic protein-7 (BMP-7) in non-union surgery. Therefore, the levels of insulin like growth factor 1 (IGF-1), platelet-derived growth factor AB (PDGF-AB) and transforming growth factor beta (TGF-ß) were compared between patients with the gold standard use of autologous bone graft (ABG) and those with additional application of BMP-7 as part of the diamond concept. PATIENTS AND METHODS: Between 2009 and 2014, of the 153 patients with tibial and femoral non-unions, a matched pair analysis was performed to compare the serological cytokine expressions. Blood samples were collected preoperatively, 1, 2 and 6 weeks as well as 3 and 6 months after non-union surgery. Matching criteria were smoking status, fracture location, gender, age and body mass index (BMI). Patients in G1 (n=10) were treated with ABG and local BMP-7 while their matching partners in G2 (n=10) received ABG only. The routine clinical and radiologic follow-up was 1 year. RESULTS: Although the IGF-1 quantification in G2 showed higher pre- and postoperative values compared to G1 (p<0.05), the courses of both groups were similar. Likewise, PDGF-AB and TGF-ß expressions appeared similar in G1 and G2 with peaks in both groups at 2 weeks follow-up. Osseous consolidation was assessed in all operated non-unions. The adjunct application of BMP-7 did not cause any pathologic cytokine expression. CONCLUSION: Similar expressions of the serum cytokines IGF-1, PDGF-AB and TGF-ß were demonstrated in non-union patients treated with ABG and additional application of BMP-7 according to the diamond concept. Our findings indicate that the local application of BMP-7, which imitates the physiologic secretion of growth factors during bone regeneration, is safe and without the risk of abnormal systemic cytokine expression. Studies with higher patient numbers will have to validate these assumptions.

Validity of subjective smoking status in orthopedic patients.

PURPOSE: In this level 1 diagnostic study, we analyzed the validity of subjective smoking status and, as secondary research question, the smoking cessation adherence in orthopedic patients during a routine hospital stay of nonunion patients by measuring serum cotinine. METHODS: We included patients undergoing revision surgery due to nonunion of long bones. Patients were interviewed about their smoking status. Blood samples were taken from all the patients prior to surgery and for an additional 6 weeks following surgery. Serum levels of cotinine were measured, and coherence between subjective smoking status and objective cotinine analysis was evaluated. RESULTS: Between March 2012 and August 2014, we enrolled 136 patients. Six of the 26 "previous smokers" (23%) and four of the 65 "nonsmokers" (6%) had serum cotinine above cutoff levels. In self-labeled smokers, serum cotinine levels averaged at 2,367.4±14,885.9 ng/mL (with a median of 100 ng/mL), whereas in previous smokers the levels averaged at 4,270±19,619.4 ng/mL (with a median of 0 ng/mL) and in the nonsmokers group the levels averaged at 12±53.9 ng/mL (with a median of 0.03 ng/mL). Overall, the subjective smoking status matched serum cotinine testing in 88% of the cases. Sensitivity was 79.6% and specificity was 93.1%. Ninety-one percent of the patients with preoperative positive serum values were still positive at follow-up. CONCLUSION: In this study, we could show that subjective smoking status in orthopedic patients is predominantly reliable as validated by objective cotinine measurements; however, patients who declare themselves as "previous smokers" are at elevated risk for underreporting continued smoking and patients who smoked preoperatively are at high risk for continuing their habit. In the future, caregivers should consider introducing effective treatments for smoking cessation to smokers and furthermore offer effective treatments to maintain smoking cessation in previous smokers during their routine consultation prior to orthopedic and trauma surgery.