Complement Factor H-Related Proteins CFHR2 and CFHR5 Represent Novel Ligands for the Infection-Associated CRASP Proteins of Borrelia burgdorferi

Background: One virulence property of Borrelia burgdorferi is its resistance to innate immunity, in particular to complement-mediated killing. Serum-resistant B. burgdorferi express up to five distinct complement regulator-acquiring surface proteins (CRASP) which interact with complement regulator factor H (CFH) and factor H-like protein 1 (FHL1) or factor H-related protein 1 (CFHR1). In the present study we elucidate the role of the infection-associated CRASP-3 and CRASP-5 protein to serve as ligands for additional complement regulatory proteins as well as for complement resistance of B. burgdorferi. Methodology/Principal Findings: To elucidate whether CRASP-5 and CRASP-3 interact with various human proteins, both borrelial proteins were immobilized on magnetic beads. Following incubation with human serum, bound proteins were eluted and separated by Glycine-SDS-PAGE. In addition to CFH and CFHR1, complement regulators CFHR2 and CFHR5 were identified as novel ligands for both borrelial proteins by employing MALDI-TOF. To further assess the contributions of CRASP-3 and CRASP-5 to complement resistance, a serum-sensitive B. garinii strain G1 which lacks all CFH-binding proteins was used as a valuable model for functional analyses. Both CRASPs expressed on the B. garinii outer surface bound CFH as well as CFHR1 and CFHR2 in ELISA. In contrast, live B. garinii bound CFHR1, CFHR2, and CFHR5 and only miniscute amounts of CFH as demonstrated by serum adsorption assays and FACS analyses. Further functional analysis revealed that upon NHS incubation, CRASP-3 or CRASP-5 expressing borreliae were killed by complement. Conclusions/Significance: In the absence of CFH and the presence of CFHR1, CFHR2 and CFHR5, assembly and integration of the membrane attack complex was not efficiently inhibited indicating that CFH in co-operation with CFHR1, CFHR2 and CFHR5 supports complement evasion of B. burgdorferi

Does Anticoagulant Medication Alter Fracture-Healing? A Morphological and Biomechanical Evaluation of the Possible Effects of Rivaroxaban and Enoxaparin Using a Rat Closed Fracture Model.

Low molecular weight heparin (LMWH) is routinely used to prevent thromboembolism in orthopaedic surgery, especially in the treatment of fractures or after joint-replacement. Impairment of fracture-healing due to increased bone-desorption, delayed remodelling and lower calcification caused by direct osteoclast stimulation is a well-known side effect of unfractioned heparin. However, the effect of LMWH is unclear and controversial. Recent studies strongly suggest impairment of bone-healing in-vitro and in animal models, characterized by a significant decrease in volume and quality of new-formed callus. Since October 2008, Rivaroxaban (Xarelto) is available for prophylactic use in elective knee- and hip-arthroplasty. Recently, some evidence has been found indicating an in vitro dose independent reduction of osteoblast function after Rivaroxaban treatment. In this study, the possible influence of Rivaroxaban and Enoxaparin on bone-healing in vivo was studied using a standardized, closed rodent fracture-model. 70 male Wistar-rats were randomized to Rivaroxaban, Enoxaparin or control groups. After pinning the right femur, a closed, transverse fracture was produced. 21 days later, the animals were sacrificed and both femora harvested. Analysis was done by biomechanical testing (three-point bending) and micro CT. Both investigated substances showed histomorphometric alterations of the newly formed callus assessed by micro CT analysis. In detail the bone (callus) volume was enhanced (sign. for Rivaroxaban) and the density reduced. The bone mineral content was enhanced accordingly (sign. for Rivaroxaban). Trabecular thickness was reduced (sign. for Rivaroxaban). Furthermore, both drugs showed significant enlarged bone (callus) surface and degree of anisotropy. In contrast, the biomechanical properties of the treated bones were equal to controls. To summarize, the morphological alterations of the fracture-callus did not result in functionally relevant deficits

Untersuchung zum Einfluß gerinnungshemmender Medikation auf die Frakturheilung anhand eines standardisierten Frakturmodells der Ratte: Eine biomechanische und morphologische Studie

The possible influence of Rivaroxaban and Enoxaparin on bone-healing was studied in vivo using a standardized, closed rodent fracture-model. After pinning of the right femur and randomization, a closed transverse fracture was produced. 21 days later, the animals (n=70) were euthanized and both femora harvested. Analysis was done by biomechanical testing (three-point bending) and micro CT. Both substances showed histomorphometric alterations of the new formed callus. In contrast, the biomechanical properties of the treated bones were equal to controls. To summarize, the morphological alterations of the fracture-callus did not result in functionally relevant deficits.In der vorliegenden Studie wurde in einem standardisierten Ratten-Frakturmodell die Auswirkungen von Rivaroxaban und Enoxaparin auf die Knochenheilung untersucht. Dabei zeigte sich im Vergleich zur Kontrollgruppe keine nachvollziehbare Veränderung biomechanischer Eigenschaften. Morphologische Unterschiede des gebildeten Kallus konnten jedoch für beide Substanzen mittels Micro CT nachgewiesen werden. Zumindest die erste Phase der Frakturheilung und die Formation des Frakturhämatoms scheinen durch die untersuchten Substanzen verändert

Surgical resection and radiation therapy of desmoid tumours of the extremities: results of a supra-regional tumour centre.

Desmoid tumours of the extremity have a high recurrence rate. The purpose of this study was to analyse the outcome after resection of these tumours with special emphasis on recurrent disease and adjuvant therapeutic strategies.In this retrospective study we evaluated prognostic factors for recurrence-free survival after surgical treatment of desmoid tumours of the extremity in 27 patients with an average age of 41 years treated from 1997 to 2009. Adjuvant radiotherapy (50-60 Gy) was given in five cases with primary and in nine patients with recurrent disease. The average follow-up was 64 months.The five-year recurrence-free survival in patients with primary disease was 33%. Patients with negative resection margins tended to have a better outcome than patients with positive resection margins, but the difference between both groups was not significant (56 vs 14%, p = 0.145). In patients with positive margins, adjuvant radiotherapy did not significantly improve recurrence-free survival (40 vs 14%, p = 0.523). Patients with local recurrence had a five-year further recurrence-free survival of 47%. In those patients further recurrence-free survival was significantly better after adjuvant radiation (89 vs 25%, p = 0.015). Two thirds of all patients suffered moderate or severe complications due to the treatment regimen.Compared to desmoids of the trunk or the head and neck region, desmoids affecting the limbs show by far the worst outcome in terms of relapse or treatment-related morbidity. The importance of negative resection margins is still not clear. Particularly in recurrent desmoids adjuvant radiotherapy appears to reduce the further recurrence rate. Therefore, a general use of radiation should be considered for this high-risk group

A novel technique to treat Grisel's syndrome: Results of a simplified, therapeutical algorithm

PURPOSE: Grisel’s syndrome is a rare entity and usually develops in paediatric patients after otolaryngologic surgery or infection. It is defined as a fixed torticollis combined with a rotatory atlanto-axial subluxation. The success rate of physiotherapy is low. Conventional therapy concepts imply stage-related recommendations based on the Fielding classification (type I–IV). This classification was introduced in 1977 to assess the degree of subluxation between atlas (C1) and axis (C2). Thus, instability increases from type I to IV. Higher stages may require surgical intervention. The purpose of this study was to evaluate the value of an alternative, less invasive treatment protocol in Grisel’s syndrome. METHODS: Irrespective of the underlying Fielding type we treated five children (Fielding type I–III) by manual repositioning under general anaesthesia. Consecutively, the cervical spine was immobilized with a Minerva cast for four to eight weeks. Additional surgical treatment or immobilization in a Halo-Fixateur was not necessary. RESULTS: Overall period of treatment was reduced, even in patients with delayed diagnosis. No case of recurrence was observed within a follow-up of six months. CONCLUSIONS: Current conventional recommendations suggest invasive treatment with Halo-Fixateur in patients with higher degrees of subluxation (e.g., Fielding type III) or after delayed diagnosis. Even in those patients, this novel therapy concept enables us to achieve excellent clinical results without surgical intervention

Fully automated segmentation of callus by micro-CT compared to biomechanics

Abstract Background A high percentage of closed femur fractures have slight comminution. Using micro-CT (μCT), multiple fragment segmentation is much more difficult than segmentation of unfractured or osteotomied bone. Manual or semi-automated segmentation has been performed to date. However, such segmentation is extremely laborious, time-consuming and error-prone. Our aim was to therefore apply a fully automated segmentation algorithm to determine μCT parameters and examine their association with biomechanics. Methods The femura of 64 rats taken after randomised inhibitory or neutral medication, in terms of the effect on fracture healing, and controls were closed fractured after a Kirschner wire was inserted. After 21 days, μCT and biomechanical parameters were determined by a fully automated method and correlated (Pearson’s correlation). Results The fully automated segmentation algorithm automatically detected bone and simultaneously separated cortical bone from callus without requiring ROI selection for each single bony structure. We found an association of structural callus parameters obtained by μCT to the biomechanical properties. However, results were only explicable by additionally considering the callus location. Conclusions A large number of slightly comminuted fractures in combination with therapies that influence the callus qualitatively and/or quantitatively considerably affects the association between μCT and biomechanics. In the future, contrast-enhanced μCT imaging of the callus cartilage might provide more information to improve the non-destructive and non-invasive prediction of callus mechanical properties. As studies evaluating such important drugs increase, fully automated segmentation appears to be clinically important

Surgical resection and radiation therapy of desmoid tumours of the extremities: results of a supra-regional tumour centre

PURPOSE: Desmoid tumours of the extremity have a high recurrence rate. The purpose of this study was to analyse the outcome after resection of these tumours with special emphasis on recurrent disease and adjuvant therapeutic strategies. METHODS: In this retrospective study we evaluated prognostic factors for recurrence-free survival after surgical treatment of desmoid tumours of the extremity in 27 patients with an average age of 41 years treated from 1997 to 2009. Adjuvant radiotherapy (50–60 Gy) was given in five cases with primary and in nine patients with recurrent disease. The average follow-up was 64 months. RESULTS: The five-year recurrence-free survival in patients with primary disease was 33 %. Patients with negative resection margins tended to have a better outcome than patients with positive resection margins, but the difference between both groups was not significant (56 vs 14 %, p = 0.145). In patients with positive margins, adjuvant radiotherapy did not significantly improve recurrence-free survival (40 vs 14 %, p = 0.523). Patients with local recurrence had a five-year further recurrence-free survival of 47 %. In those patients further recurrence-free survival was significantly better after adjuvant radiation (89 vs 25 %, p = 0.015). Two thirds of all patients suffered moderate or severe complications due to the treatment regimen. CONCLUSIONS: Compared to desmoids of the trunk or the head and neck region, desmoids affecting the limbs show by far the worst outcome in terms of relapse or treatment-related morbidity. The importance of negative resection margins is still not clear. Particularly in recurrent desmoids adjuvant radiotherapy appears to reduce the further recurrence rate. Therefore, a general use of radiation should be considered for this high-risk group

Revision Arthroplasty Through the Direct Anterior Approach Using an Asymmetric Acetabular Component

Despite increasing numbers of primary hip arthroplasties performed through the direct anterior approach (DAA), there is a lack of literature on DAA revision arthroplasty. The present study was performed in order to evaluate outcomes and revision rates after revision through the DAA using an asymmetric acetabular component with optional intra- and extramedullary fixation. In a retrospective cohort study, we analyzed prospectively collected data of 57 patients (61 hips, 43 female, 18 male) who underwent aseptic acetabular component revision through the DAA with the abovementioned implant system between January 2015 and December 2017. The mean follow-up was 40 months (12–56). Survival rates were estimated using the Kaplan–Meier method. All complications were documented and functional outcomes were assessed pre- and postoperatively. Kaplan–Meier analysis revealed an estimated five-year implant survival of 97% (confidence interval CI 87–99%). The estimated five-year survival with revision for any cause was 93% (CI 83–98%). The overall revision rate was 6.6% (n = 4). Two patients had to undergo revision due to periprosthetic infection (3.3%). In one patient, the acetabular component was revised due to aseptic loosening four months postoperatively. Another patient suffered from postoperative iliopsoas impingement and was treated successfully by arthroscopic iliopsoas tenotomy. Two (3.3%) of the revised hips dislocated postoperatively. The mean Harris Hip Score improved from 35 (2–66) preoperatively to 86 (38–100) postoperatively (p < 0.001). The hip joint’s anatomical center of rotation was restored at a high degree of accuracy. Our findings demonstrate that acetabular revision arthroplasty through the DAA using an asymmetric acetabular component with optional intra- and extramedullary fixation is safe and practicable, resulting in good radiographic and clinical midterm results