IL-7 receptor signaling drives human B-cell progenitor differentiation and expansion.

Although absence of interleukin-7 (IL-7) signaling completely abrogates T and B lymphopoiesis in mice, patients with severe combined immunodeficiency caused by mutations in the IL-7 receptor α chain (IL-7Rα) still generate peripheral blood B cells. Consequently, human B lymphopoiesis has been thought to be independent of IL-7 signaling. Using flow cytometric analysis and single-cell RNA sequencing of bone marrow samples from healthy controls and patients who are IL-7Rα deficient, in combination with in vitro modeling of human B-cell differentiation, we demonstrate that IL-7R signaling plays a crucial role in human B lymphopoiesis. IL-7 drives proliferation and expansion of early B-cell progenitors but not of pre-BII large cells and has a limited role in the prevention of cell death. Furthermore, IL-7 guides cell fate decisions by enhancing the expression of BACH2, EBF1, and PAX5, which jointly orchestrate the specification and commitment of early B-cell progenitors. In line with this observation, early B-cell progenitors of patients with IL-7Rα deficiency still expressed myeloid-specific genes. Collectively, our results unveil a previously unknown role for IL-7 signaling in promoting the B-lymphoid fate and expanding early human B-cell progenitors while defining important differences between mice and humans. Our results have implications for hematopoietic stem cell transplantation strategies in patients with T- B+ severe combined immunodeficiency and provide insights into the role of IL-7R signaling in leukemogenesis.

Defects in B-lymphopoiesis and B-cell maturation underlie prolonged B-cell depletion in ANCA-associated vasculitis.

OBJECTIVES: B-cell depletion time after rituximab (RTX) treatment is prolonged in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) compared with other autoimmune diseases. We investigated central and peripheral B-cell development to identify the causes for the defect in B-cell reconstitution after RTX therapy. METHODS: We recruited 91 patients with AAV and performed deep phenotyping of the peripheral and bone marrow B-cell compartment by spectral flow and mass cytometry. B-cell development was studied by in vitro modelling and the role of BAFF receptor by quantitative PCR, western blot analysis and in vitro assays. RESULTS: Treatment-naïve patients with AAV showed low transitional B-cell numbers, suggesting impaired B-lymphopoiesis. We analysed bone marrow of treatment-naïve and RTX-treated patients with AAV and found reduced B-lymphoid precursors. In vitro modelling of B-lymphopoiesis from AAV haematopoietic stem cells showed intact, but slower and reduced immature B-cell development. In a subgroup of patients, after RTX treatment, the presence of transitional B cells did not translate in replenishment of naïve B cells, suggesting an impairment in peripheral B-cell maturation. We found low BAFF-receptor expression on B cells of RTX-treated patients with AAV, resulting in reduced survival in response to BAFF in vitro. CONCLUSIONS: Prolonged depletion of B cells in patients with AAV after RTX therapy indicates a B-cell defect that is unmasked by RTX treatment. Our data indicate that impaired bone marrow B-lymphopoiesis results in a delayed recovery of peripheral B cells that may be further aggravated by a survival defect of B cells. Our findings contribute to the understanding of AAV pathogenesis and may have clinical implications regarding RTX retreatment schedules and immunomonitoring after RTX therapy.

Nonpermissive bone marrow environment impairs early B-cell development in common variable immunodeficiency.

Common variable immunodeficiency (CVID) is a disease characterized by increased susceptibility to infections, hypogammaglobulinemia, and immune dysregulation. Although CVID is thought to be a disorder of the peripheral B-cell compartment, in 25% of patients, early B-cell development in the bone marrow is impaired. Because poor B-cell reconstitution after hematopoietic stem cell transplantation has been observed, we hypothesized that in some patients the bone marrow environment is not permissive to B-cell development. Studying the differentiation dynamics of bone marrow-derived CD34+ cells into immature B cells in vitro allowed us to distinguish patients with B-cell intrinsic defects and patients with a nonpermissive bone marrow environment. In the former, immature B cells did not develop and in the latter CD34+ cells differentiated into immature cells in vitro, but less efficiently in vivo. In a further group of patients, the uncommitted precursors were unable to support the constant development of B cells in vitro, indicating a possible low frequency or exhaustion of the precursor population. Hematopoietic stem cell transplantation would result in normal B-cell repopulation in case of intrinsic B-cell defect, but in defective B-cell repopulation in a nonpermissive environment. Our study points to the importance of the bone marrow niche in the pathogenesis of CVID.

10-year follow-up of the Columbus knee prostheses system in a prospective multicenter study.

INTRODUCTION: As endpoint of a prospective multicenter 10-year documentation using the Columbus system, this evaluation carried out results of clinical scores (Knee Society Score and Oxford Knee Score), an evaluation of radiological imaging, survival rates and a collection of complication statistics. MATERIALS AND METHODS: There was a multicenter prospective recruitment of consecutive patients with the indication for total knee replacement (TKR). Preoperatively and 10 years after implantation, clinical scores, range of motion and radiological imaging was performed. During this period, a detailed documentation of complications was made. RESULTS: A total of 210 patients were recruited in 5 centers. 140 patients were available for endpoint examination 10 years after surgery. A survival rate of 96.6% (CI 95%) for the implanted Columbus prostheses after 10 years was demonstrated. Cumulative KSS showed an improvement of 75.3 (± 38.1) points and was highly significant (p < 0.0001, t test). The average functional improvement in the Oxford score was 20.6 (± 9.5) points and was also highly significant (p < 0.0001). The ROM improved from 106.5° (± 20.5) preoperatively to 116.0° (± 11.5) (p < 0.0001, t test). There were no implant-related complications as well as no new complication documented between 5- and 10-year follow-up. CONCLUSIONS: The endpoint analysis after an observation period of 10 years provided good clinical and radiographic results. In particular, an excellent survival rate of 96.6% after 10 years was demonstrated. The data published in this study are the first to be available in a prospective multicenter study on this system, which leads to a high level of clinical significance.

Inhibition of the anti-apoptotic protein MCL-1 severely suppresses human hematopoiesis

BH3-mimetics inhibiting anti-apoptotic BCL-2 proteins represent a novel and promising class of antitumor drugs. While the BCL-2 inhibitor venetoclax is already FDA-approved, BCL-XL and MCL-1 inhibitors are currently in early clinical trials. To predict side effects of therapeutic MCL-1 inhibition on the human hematopoietic system, we used RNAi and the small molecule inhibitor S63845 on cord blood-derived CD34+ cells. Both approaches resulted in almost complete depletion of human hematopoietic stem and progenitor cells. As a consequence, maturation into the different hematopoietic lineages was severely restricted and CD34+ cells expressing MCL-1 shRNA showed a very limited engraftment potential upon xenotransplantation. In contrast, mature blood cells survived normally in the absence of MCL-1. Combined inhibition of MCL-1 and BCL-XL resulted in synergistic effects with relevant loss of colony-forming HSPCs already at inhibitor concentrations of 0.1 µM each, indicating "synthetic lethality" of the two BH3-mimetics in the hematopoietic system.

Rehabilitation before regenerative cartilage knee surgery: a new prehabilitation guideline based on the best available evidence.

INTRODUCTION: Focal cartilage defects are an increasingly relevant clinical problem especially in athletes. Cartilage regenerative surgery (CRS) including microfracture and autologous chondrocyte implantation (ACI) to treat such isolated cartilage defects in the knee joint has been well established in the last two decades. In contradiction to high-level evidence concerning the surgical technique, cell-related issues, and clinical results, the knowledge about the optimal rehabilitation process is still sparse although the importance of optimizing the rehabilitation process has recently led to new research focus in this field. The preoperative time frame may be used to start rehabilitation which may fasten the postoperative recovery and optimize clinical outcome ("Prehabilitation"-PREHAB). The aim of this article, therefore, was to review the available literature on prehabilitation concepts and to present a prehabilitation guideline for CRS patients based on the best evidence available. METHODS: A systemic literature research was conducted on rehabilitation for cartilage regenerative surgery as well as prehabilitation in knee joint procedures. From the available literature a prehabilitation concept was generated and tested in 10 ACI patients. RESULTS: As the literature search found no studies addressing prehabilitation in CRS patients, an evidence-based PREHAB program has been compiled based on the available evidence from (a) studies addressing postoperative rehabilitation in CRS patients and (b) PREHAB studies on other knee procedures including TKA. This presented prehabilitation guideline has been tested in > 50 CRS patients and was found to be feasible as all of the patients showed a good compliance and were able to perform the protocol as suggested. CONCLUSION: The presented PREHAB regimen may serve clinicians as a guideline for early rehabilitation of their CRS patients. Obviously, further research is mandatory to quantify its clinical effect and to demonstrate its cost-effectiveness and benefits in surgically treated patients.

Evaluation of hemodynamic goal-directed therapy to reduce the incidence of bone cement implantation syndrome in patients undergoing cemented hip arthroplasty - a randomized parallel-arm trial.

BACKGROUND: The bone cement implantation syndrome (BCIS) is a frequent and potentially disastrous intraoperative complication in patients undergoing cemented hip arthroplasty. Several risk factors have been identified, however randomized controlled trials to reduce the incidence of BCIS are still pending. We hypothesized that goal-directed hemodynamic therapy guided by esophageal Doppler monitoring (EDM) may reduce the incidence of BCIS in a randomized, controlled parallel-arm trial. METHODS: After approval of the local ethics committee, 90 patients scheduled for cemented hip arthroplasty at the Medical Center - University of Freiburg were randomly assigned to either standard hemodynamic management or goal-directed therapy (GDT) guided by an esophageal Doppler monitoring-based algorithm. The primary endpoint was the incidence of overall BCIS including grade 1-3 after cementation of the femoral stem. Secondary endpoints included cardiac function, length of hospital stay and postoperative complications. RESULTS: Ninety patients were finally analyzed. With regards to the primary endpoint, the overall incidence of BCIS showed no difference between the GDT and control group. Compared to the control group, patients of the GDT group showed a higher cardiac index before and after bone cement implantation (2.7 vs. 2.2 [l●min- 1●m- 2]; 2.8 vs. 2.4 [l●min- 1●m- 2]; P = 0.003, P = 0.042), whereas intraoperative amount of fluids and mean arterial pressure did not differ. CONCLUSIONS: The implementation of a specific hemodynamic goal-directed therapy did not reduce the overall incidence of BCIS in patients undergoing cemented hip arthroplasty. TRIAL REGISTRATION: This randomized clinical two-arm parallel study was approved by the local Ethics Committee, Freiburg, Germany [EK 160/15, PI: U. Goebel] and registered in the German Clinical Trials Register ( DRKS No. 00008778 , 16th of June, 2015).

[5-year follow-up of 210 Columbus knee prostheses : A prospective multicentre study]. / 5-Jahres-Follow-up von 210 Columbus-Knietotalendoprothesen : Eine prospektive multizentrische Studie.

INTRODUCTION: As part of 10-year documentation using the Columbus system, the interim evaluation was carried out 5 years after implantation with a collection of clinical scores, evaluation of radiological imaging and collection of statistics concerning complications. METHODS: There was a multicentre prospective recruitment of consecutive patients with the indication of implantation of a surface replacement prosthesis (Columbus CR, Deep Dish fixed inlay). Preoperatively, clinical scores were recorded (KSS and Oxford score). Five years postoperatively a new evaluation of clinical scores, the range of motion (ROM) and a radiological check-up including full leg imaging under load was performed. During this period, detailed complication documentation was made. RESULTS: A total of 210 patients were recruited in five centres. 187 patients were available for examination 5 years after surgery. Cumulative KSS increased from 87.5 (±26.6) preoperatively to 170 (±29.1) 5 years postoperatively. The cumulative KSS improvement was 81.5 (±35.2) points and was highly significant (p < 0.0001; t­test). The average functional improvement in the Oxford score between the preoperative and 5­year follow-up was 21.7 (±8.8) points and was also highly significant (p < 0.0001). The ROM improved from 106.3° (±20.2) preoperatively to 114.0° (±12.1) 5 years postoperatively (p < 0.0001; t test). Five years after implantation, the average mechanical leg axis was 178.0° (±2.1). There was no clinically apparent or native radiologic visible aseptic loosening of the femoral or tibial joint component. There were 33 complications, but no implant-related complications such as inlay dislocation, material fracture or aseptic loosening. In total, 6 revision surgeries were performed during the follow-up period, which corresponds to a survival rate of 97.1% (CI 95%) for the implanted Columbus knee in the present patient collective for 5 years. CONCLUSION: The interim analysis at 5 years of long-term observation of the Columbus system provided good clinical and radiographic results.

Analysis of the hemostatic potential of modern topical sealants on arterial and venous anastomoses: an experimental porcine study.

One of the widely accepted adjunctive agents in the variety of surgical modalities are sealants. Our study aim was to compare four commonly used modern sealants in a standardized experimental setting to assess their feasibility, and hemostatic efficacy in vascular anastomosis. Forty landrace pigs (weight: 24.7 ± 3.8 kg) were randomized into the control (n = 8) and four sealant groups; TachoSil® (n = 8), Tissucol Duo® (n = 8), Coseal® (n = 8), and FloSeal® (n = 8). After doing a portal vein end-to-end anastomosis as well as stitches of aortic incision, the sealants were applied on anastomotic site. The control group was left intact. In portal vein anastomosis, the sealants led to a complete hemostasis significantly better than control group. The mean of blood loss was also significantly reduced. In successful subgroups, there was a difference in the mean-time to reach complete hemostasis ranging from 15 s in Coseal® to 76 s in FloSeal® group (p < 0.05). In aortotomy experiments, except Tissucol Due®, which had insufficient hemostasis, other sealants led to a complete hemostasis. The mean blood loss was significantly reduced in sealants groups as well. The four sealants are effective in reducing the suture-hole bleeding in portal vein anastomosis. However, the hemostatic potential is heterogeneous among sealants. This means that "one-size-fits-all" approach is not appropriate for application of sealants in diversity of vascular surgery and it should be based on the type and the severity of injury and the structure of tissue. Comparison of hemostasis efficacy of four modern sealants (TachoSil®, Tissucol Duo®, Coseal®, and FloSeal®) in vascular anastomosis in porcine model. The figures below show the total blood loss (g) in the control and sealant groups after aortotomy (left) and portal vein anastomosis (right). The mean of blood loss decreased significantly by the usage of sealants in both experiment groups as compared to control group (*: p < 0.05; sealant groups vs. control group). 1. The right column shows the mean of blood loss (g) in all experiments in each group. 2. The middle column presents the subgroup with unsuccessful hemostasis at the end of observation time (Tmax = 20 sec. for aortotmy and 300 sec. for portal vein anastomosis). 3. The left column shows mean of total blood loss in subgroups with successful hemostasis during observation time (20 sec for aortotomy and 300 sec for portal vein).

Comparative analysis of locking plate versus hook plate osteosynthesis of Neer type IIB lateral clavicle fractures.

INTRODUCTION: Controversy exists on optimal operative treatment of vertically unstable Neer IIB lateral clavicle fractures. Aim of this study was to analyse and compare clinical and radiological results and complications of locking plate osteosynthesis (LPO) versus hook plate osteosynthesis (HPO) with acromioclavicular joint (ACJ) stabilization. The hypothesis was, that HPO would recreate coracoclavicular stability more effectively and potentially lead to a superior outcome. METHODS: This retrospective, observational cohort study included 32 patients (19 HPO, 13 LPO) with a mean age of 44.1 ± 14.2 years at surgery. The mean follow-up period was 54.2 months (range 25.2-111.4 months). Besides standard radiography, bilateral coracoclavicular distances were assessed by means of preoperative and follow-up stress radiographs after implant removal. Clinical outcome measures included the Constant score (CS), the Oxford shoulder score (OSS), the subjective shoulder value (SSV) and the Taft score (TS). RESULTS: Bone union occurred in all but one patient and proved to occur delayed in five patients (15.6%). Radiographical healing required a mean of 4.2 ± 4.0 months irrespective of the type of osteosynthesis. At follow-up, mean coracoclavicular distance was increased by 34% (±36) without significant differences between both groups. HPO patients obtained a significantly lower TS (HPO: 9.5 ± 1.5 points, LPO: 11.1 ± 1.3 points; p = 0.005). Other mean score values did not differ (CS: 90.1 ± 7.4 points, OSS: 43.2 ± 9.2 points, SSV: 91.1 ± 14.7%). Sixteen patients (50.0%) experienced complications. Overall prevalence of complications was significantly higher in the HPO group (p = 0.014). CONCLUSIONS: Both HPO and LPO were equally effective in relation to restoration of vertical stability, overall functional outcome and fracture consolidation in treatment of Neer IIB fractures. Contrary to our hypothesis, HPO was not associated with superior recreation of the coracoclavicular distance. Considerable drawbacks of HPO were an inferior ACJ-specific outcome (Taft-Score) and a higher overall complication rate. Level of evidence IV.

Smoking and unstable hinge fractures cause delayed gap filling irrespective of early weight bearing after open wedge osteotomy.

PURPOSE: The purpose of this study was to examine the osteotomy gap filling rate with new bone after open wedge high tibial osteotomy (HTO) without bone graft and the effects of smoking, lateral hinge fracture, and early full weight bearing. METHODS: A prospective series (N = 70) of open wedge HTOs with the TomoFix plate (DePuy Synthes, Umkirch, Germany) was performed. Radiologic follow-up examinations took place postoperatively, after 6 and 12 weeks, and after 6, 12, and 18 months to measure osteotomy gap filling at each follow-up. Bone healing was compared in smokers versus nonsmokers who underwent open wedge HTOs with intact lateral hinges. Fractured lateral hinges were classified according to the Takeuchi classification and separately analyzed regarding bone healing. Patients were randomly assigned to undergo early (11 days) or standard (6 weeks) full-weight-bearing rehabilitation. RESULTS: A delay in the osteotomy gap filling rate between smokers and nonsmokers could be observed at all follow-up periods, but differences were not significant. A fracture of the lateral hinge was found in 39% of the patients. A type I fracture was observed in 14% of patients, a type II fracture was observed in 13%, and a type III fracture was found in 6%. The highest increase in the osteotomy gap filling rate was observed between 12 weeks and 6 months after surgery in patients with intact lateral hinges. For patients with unstable type II fractures, the highest increase in the gap filling rate was delayed until 6 to 12 months. Early full weight bearing had no effect on the gap filling rate in any of the patient groups evaluated. CONCLUSIONS: This study shows that osteotomy gap filling after open wedge HTO is delayed in smokers and in patients in whom opening of the gap resulted in unstable lateral hinge fractures. Early full weight bearing did not have a significant effect on the gap filling rate. LEVEL OF EVIDENCE: Level III, prognostic study.

Digital templating in total knee and hip replacement: an analysis of planning accuracy.

PURPOSE: The aim of this study was to determine how well pre-operative size selection for total knee and hip arthroplasties based on the digital imaging with and without additional referencing correlated with the size actually implanted. METHODS: Size selection planning of total knee arthroplasty by digital templating was documented in 46 cases with reference ball (group A) and in 48 cases without ball (group B). In addition, prospective analysis of pre-operative planning was conducted for 52 acetabular components with reference ball (group C) and 69 without ball (group D) as well as stem planning in 38 cases with ball (group E) and 54 cases without ball (group F). The data were analysed and compared with the size of the final component selected during surgery. RESULTS: The correlation between planned and implanted size for total knee arthroplasty in group A resulted in femoral anteroposterior (AP) r = 0.8622 and lateral r = 0.8333 and in group B AP r = 0.4552 and lateral r = 0.6950. Tibial in group A was AP r = 0.9030 and lateral r = 0.9074 and in group B AP r = 0.7000 and lateral r = 0.6376. For the acetabular components, the results in group C were r = 0.5998 and group D r = 0.6923. For stems, group E was r = 0.5306 and group F r = 0.5786. No correlation between BMI and the difference between planned and implanted size was found in any of the groups. CONCLUSION: In the case of total hip arthroplasty there was a relatively low correlation between planned and implanted sizes with or without reference ball. For total knee arthroplasties the already high precision of size planning was further improved by the additional referencing with a reference ball.

Periprosthetic joint infection--effect on quality of life.

PURPOSE: Relatively little is known about the extent to which periprosthetic joint infections (PJI) affect the patient's long-term quality of life (QoL). Our study aim was to assess the effect of a periprosthetic infection on our patients' QoL. METHODS: We collected data retrospectively of patients who had undergone surgery in our institution between 2006 and 2011. To capture their overall QoL, we telephoned the patients who could be reached and asked them the questions on the SF-12 questionnaire. RESULTS: In 84 patients (53 male, 31 female, 43 TKA and 41 THA), 88 % of the hip infections and 62 % of the knee infections had been successfully treated. The hip infections' cure rate was significantly higher than that of the knee joint infections. The average SF-12 score was 36.2 points on the physical scale and 52 on the mental scale. The difference in QoL between patients with and without successful infection therapy was not significant, nor did the site of the infection (knee or hip) influence QoL significantly. Comparison of our patients' QoL data to that from the general population revealed a significant difference in the physical scale but not the mental scale. CONCLUSION: From these results QoL is substantially reduced after a prosthetic infection. We did however observe that post-Girdelstone procedure patients or those with an arthrodesis attained an acceptable QoL, and that those methods remain therapeutic alternatives as far as patient-perceived QoL is concerned.

Rotational limb alignment changes following total knee arthroplasty.

PURPOSE: The aim of the present study was to assess the changes in rotational alignment introduced by total knee arthroplasty (TKA) and the reproducibility of pre- and postoperative CT measurements of rotational limb alignment. METHODS: For this purpose we analyzed data from 196 consecutive cruciate-retaining, fixed bearing Columbus TKA procedures. Both pre- and postoperative scans torsion difference CT scans were available for measurements in 89 cases. Using these CT scans the neck-malleolar angle (NMA), the femoral posterior condylar angle (fPCA), the tibial posterior condylar axis (tPCA) and the tibial torsion angle (TTA) were independently assessed by three raters. CT scans were re-evaluated 8 weeks later by the most experienced rater for assessment of intraobserver agreement. RESULTS: Measurements of all angles were prone to high standard deviations reflecting interindividual variability. Mean fPCA changed from 1.3° to 2.7° internal rotation preoperatively to 0.1°-1.9° internal rotation postoperatively. Based on a relative external rotation of the tibial base plate as compared to the preoperative situation, we found a relative internal rotation of the postoperative NMA and tibial torsion of 3°-5.4° and 6°-7.5°, respectively. Intra- and interobserver agreement was strong for all angles assessed (ICCs 0.7-1.0) except for fPCA (ICC 0.2-0.6). However, mean absolute measurement differences for fPCA were clinically acceptable (1.2°-2.6°). CONCLUSIONS: Reproducibility of CT rotational limb alignment measurements was found to be clinically acceptable. Rotational alignment of the femoral and even more so of the tibial component will ultimately affect the rotational alignment of the entire limb-at least when fixed bearings are used. LEVEL OF EVIDENCE: Diagnostic study, Level III.

Modular sleeves with ceramic heads in isolated acetabular cup revision in younger patients-laboratory and experimental analysis of suitability and clinical outcomes.

PURPOSE: One possibility in hip arthroplasty revisions is to combine a modular ceramic head with an adapter or sleeve in isolated acetabular cup replacement. This study consisted of an experimental part to analyse the reliability of taper damage predictions, and a clinical part to analyse the outcomes of modular ceramic head implantation in a case series of isolated cup replacements. METHODS: Analysis of scratch size on 11 explanted hip stems were examined macroscopically and by stereomicroscopy to classify damage to the conical taper. The second part consisted of a prospective analysis of isolated cup revisions using a modular ceramic head, performed in two orthopedic centres. RESULTS: Analysis of scratch size on the taper yielded inter-observer correlations of 0.545-0.909; comparison with stereomicroscopic data recordings yielded a moderate correlation, with values between 0.545 and 0.090. The clinical study included 47 isolated acetabular cup revisions involving modular ceramic heads. Ceramic head failure did not occur during the average clinical and radiological observation period of 26 months. Mean Harris Hip Score (HHS) at follow-up was 70 points. CONCLUSION: From these results, it can be concluded that damage to the implanted stem taper cannot be reliably predicted intraoperatively. Nevertheless, the clinical outcomes did show that there were no problems with the ceramic heads over the short observation period. The application of modular ceramic heads in younger patients requiring isolated cup replacement requires proper risk-benefit analysis, but is possible and appears to be a safe procedure.

Effects of muscle-equivalent forces on the biomechanical behavior of proximal femur fracture models: a pilot study on artificial bones.

INTRODUCTION: There has been extensive analysis of the influence of muscle forces and their effects on the biomechanical behavior of the proximal femur. Nevertheless, these forces have only been taken into account in a handful of biomechanical studies in the field of traumatology. The aim of this study was to analyze the biomechanical behavior of two typical fracture models of the proximal femur based on muscle-equivalent forces. METHOD: Plate osteosynthesis was performed on two groups of artificial femora to stabilize either a trochanteric osteotomy (n= 5) or a femur shaft osteotomy (n = 5). After fixation axial loading was applied to the constructs first without muscle-equivalent forces and then with the addition of these forces (abductor groups and vastus lateralis). Displacement at the osteotomy site and the stiffness of the whole construct were measured during loading. RESULTS: Comparison of the two loading modes revealed no significant differences for displacement or stiffness for the trochanteric fractures. For the femur shaft fractures, a significant difference was found for displacement (p = 0.023) and stiffness (p = 0.003) with or without muscle-equivalent forces. CONCLUSION: The loading protocol for implant testing on femur shaft fractures should include muscle-equivalent forces. For trochanteric fractures, consideration of muscle forces is not entirely necessary since they will have little effect on the results, for example, when comparing implants.

Risk of graft fracture after dorso-ventral thoraco-lumbar spondylodesis: is there a correlation with graft size?

STUDY DESIGN: Retrospective clinical study in patients with dorso-ventral thoraco-lumbar spondylodesis. OBJECTIVE: To investigate whether the ratio between graft cross sectional area and the surface area of the adjacent endplates has any effect on the midterm stability of the spondylodesis. Dorso-ventral spondylodesis in the region of the thoraco-lumbar spine is one of the most frequent operations in orthopaedic surgery. Anterior stabilization with autologous iliac crest graft currently is a standard approach in many hospitals. Although numerous recommendations are given how to perform this technique, no clinical advice is available with regard to minimum graft size. METHODS: Sixty-four-slice CT-scans were obtained from 82 patients 4-12 months after posterior spondylodesis with anterior implantation of iliac crest graft and stabilization with an internal fixator. The scans were analyzed using image analysis software. First, the cross sectional area of the graft was calculated and then the surface area of the adjacent endplates. The ratio between graft cross sectional area and endplate surface area was then calculated from these two values. The grafts were then evaluated in sagittal reconstruction for signs of fracture. RESULTS: The probability for graft fracture in autologous tricortical grafts was >0.1% (p < 0.001) if the graft cross sectional area exceeded 23.9% of the surface area of the adjacent endplates. Patients with lower ratio values had a higher fracture risk and below a value of 10% all grafts fractured. CONCLUSION: The relationship between graft cross sectional area and adjacent endplate area has an important effect on graft midterm stability in ventral spondylodesis of the thoraco-lumbar spine. In our opinion, the risk of graft fractures in dorso-ventral spondylodesis can be reduced by implantation of an appropriately sized graft without any additional procedures or instrumentation.

High complication rate after biplanar open wedge high tibial osteotomy stabilized with a new spacer plate (Position HTO plate) without bone substitute.

PURPOSE: We performed a prospective clinical and radiographic evaluation after open wedge high tibial osteotomy (HTO) using the new Position HTO plate (Aesculap, Tuttlingen, Germany) without bone transplantation. METHODS: Thirty-five open wedge HTOs with the Position HTO plate were performed without bone wedges. The mean patient age was 44.6 ± 9.2 years at the time of osteotomy, which was planned with mediCAD II software (Hectec, Niederviehbach, Germany). The Hospital for Special Surgery score, Lysholm-Gillquist score, Tegner activity level, and International Knee Documentation Committee subjective score were used for clinical assessment. We evaluated radiographs obtained preoperatively and at 2, 6, and 12 months postoperatively using full-weight-bearing anteroposterior whole-leg views and anteroposterior and lateral views of the knee. For statistical analyses, JMP 8.0.1 (SAS, Cary, NC) was used. RESULTS: We observed an overall complication rate of 34% and a plate-related complication rate of 23%. Plate-related complications included loss of correction, fracture of the tibial plateau, screw failure, malunion, and fracture of the lateral cortical bone. A significant difference in the mechanical tibiofemoral angle of -1.3° ± 1.4° (P < .001) was found between the follow-up at 2 and 6 months. The mean Hospital for Special Surgery score was 74.8 ± 11.7 preoperatively, and it increased to 87.8 ± 11.0 (P < .001). The mean score on the Lysholm-Gillquist knee functional scoring scale was 55.5 ± 21.7 preoperatively, and it improved to 73.0 ± 23.9 (P < .001). The Tegner activity level was 2.6 ± 0.9 preoperatively, and it improved significantly at final follow-up to 3.7 ± 1.8 (P < .02). The International Knee Documentation Committee subjective score was 43.0 ± 14.9 preoperatively, and it increased to 66.1 ± 21 (P < .001). CONCLUSIONS: We have shown a high plate-related complication rate and a significant loss of correction between 2 and 6 months of follow-up after open wedge HTO using the new Position HTO plate without bone wedges. The preoperatively planned mechanical tibiofemoral angle was not achieved. Despite these complications, the clinical outcome improved significantly. The Position HTO plate cannot be recommended with the presented technique. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Does the extent of prebending affect the stability of femoral shaft fractures stabilized by titanium elastic nails? A biomechanical investigation on an adolescent femur model.

BACKGROUND: Elastic stable intramedullary nailing (ESIN) is a common procedure for stabilization of femoral shaft fractures in childhood. Prebending of the nail is generally recommended to achieve optimal nail tension at the fracture site. To our knowledge there are no published data on the effects of prebending on stability. The purpose of this biomechanical study was to compare the effects of different degrees of prebending on the stability of transverse femoral fractures after ESIN using a bone model. METHODS: Standardized transverse midshaft fractures were created in 20 synthetic, biomechanically validated adolescent bones (4th Generation Composite Femur--Sawbones Europe AB, Sweden) that were stabilized with 2 titanium nails (TEN) each (4 mm diameter, Synthes) and inserted in standardized retrograde technique. The 4 test series addressed nail prebending at 0 degree, 30 degrees, 45 degrees, and 60 degrees. The models were tested biomechanically in 4-point bending in the coronal and sagittal planes, relative stiffness was determined and analyzed statistically. The level of significance was set at P < 0.05. RESULTS: Comparison of the individual groups showed no significant differences in stiffness for different degrees of prebending in the coronal plane. Significantly reduced stiffness was found in the sagittal plane for the group with 60-degree prebending compared with the 0-degree, 30-degree, and 45-degree prebending groups. Intragroup comparison in the coronal and sagittal planes yielded a significantly reduced stiffness in the sagittal plane compared with the coronal plane in the group with 60-degree prebending. The 45-degree prebending group showed a similar tendency and in the 0-degree and 30-degree prebending groups there were no significant differences. CONCLUSIONS: On a synthetic bone model, prebending of TEN was found to affect the stability of transverse fractures of the femoral shaft, whereby indiscriminate prebending will reduce stability in the sagittal plane.Despite limited extrapolation of the findings to the in vivo situation, it can be stated that prebending of TEN by 0 to 30 degrees offers the greatest stability in the coronal and sagittal planes for transverse fractures of the femoral shaft.