Erratum to "Evaluation of MoPyC-prosthesis implantation and the use of angular stable plates in the treatment of comminuted radial head fractures" [J. Orthop. 16 (2019) 288-293].

[This corrects the article DOI: 10.1016/j.jor.2019.03.002.].

[Conservative treatment options for non-unions]. / Konservative Therapieoptionen der Pseudarthrosen.

BACKGROUND: Non-unions occur in 5-10% of all fractures, whereby there is a large variability in the rate with respect to the anatomical location. All non-unions have in common that without any further medical treatment no healing can be expected, independent of the time. There is a wide range of surgical approaches for treatment of these extremely complex pathological situations, which are successful in 75-85% of the cases. Besides surgical approaches there are various conservative treatment options, which should be considered in every treatment planning. Vital non-unions sometimes shows a very good response to noninvasive procedures, particularly in the early stages. METHODS AND RESULTS: Healing can be achieved even by using basic medical measures, such as optimization of comorbidities, reduction of risk factors and conditioning of an extremity. More elaborate procedures, such as low-intensity pulsed ultrasound (LIPUS) or extracorporeal shockwave therapy (EWST) can make surgical treatment superfluous in 63-94% of cases and show no or only very few side effects at a much lower cost; however, a high patient compliance level is necessary when performing these procedures. As optimal preconditions for a successful conservative treatment, non-unions should be stable due to an adequate osteosynthesis and free of infections, should not show any malalignment and the defect area should be less than 5 mm. CONCLUSION: In every individual case an experience physician should determine whether a conservative treatment option is possible for this complex condition.

Use of Masquelet technique in treatment of septic and atrophic fracture nonunion.

BACKGROUND: Treatment of atrophic non-unions and large bone defects or infections remains a challenging task for the treating surgeon. In the herein study, we present our experience of the 'Masquelet technique' according to the 'diamond concept' for the treatment of complex long bone reconstruction procedures. METHODS: Between February 2010 and March 2015, 150 patients (mean age 51.4) with atrophic and- /or infected non-unions were included in this prospective study. All patients received autologous bone graft, a graft expander (TCP (tricalcium phosphate)) and BMP (bone morphogenic protein). Clinical and radiological parameters were assessed at 6 weeks, and at 3, 6 and 12 months. The SF-12 questionnaire was used to evaluate the subjective health of patients. RESULTS: A successful bony consolidation of the non-unions was observed in 120 (80%) cases with a median healing time of 12.1 months. The mean defect gap was 4.4cm. Initial infection was documented in 54 cases. The most frequently identified pathogen was staphylococcus epidermidis and staphylococcus aureus. A successful removal of microorganisms with subsequent healing was achieved in 39 cases (72%). The SF-12 scores of subjective physical and mental health increased from PCS 31.5 preoperatively to 36.7 one year postoperatively, while MCS increased from 45.5 to 48.7. CONCLUSIONS: Our study showed that the Masquelet technique according to the 'diamond concept' is a valid method to treat complex atrophic non-unions with large bone defects and associated infection. Following the principles of the 'diamond concept' (targeted optimization of tissue engineering and bone regeneration) a high rate of success can be expected in these difficult reconstruction cases.

Evaluation of MoPyC-prosthesis implantation and the use of angular stable plates in the treatment of comminuted radial head fractures.

OBJECTIVE: Comminuted radial head fractures are disproportionately often accompanied by injuries of the bone or ligaments and can be treated in different ways. METHODS: 15 patients with a comminuted radial head fracture were treated with an angular stable plate (=G1) and 8 with a MoPyC-prosthesis (=G2). RESULTS: G1 shows an average Morrey-score of 83,87 points. Complications occurred in 5/15 patients. Within G2 an average Morrey-score of 86 was achieved. Complications could be shown in 2/8 patients. CONCLUSION: Both the treatment provides a clear individual benefit for the patients and predict promising results for the treatment of comminuted radial head fractures.

Evaluation of MoPyC-prosthesis implantation and the use of angular stable plates in the treatment of comminuted radial head fractures.

OBJECTIVE: Comminuted radial head fractures are disproportionately often accompanied by injuries of the bone or ligaments and can be treated in different ways. METHODS: 15 patients with a comminuted radial head fracture were treated with an angular stable plate (=G1) and 8 with a MoPyC-prosthesis (=G2). RESULTS: G1 shows an average Morrey-score of 83,87 points. Complications occurred in 5/15 patients. Within G2 an average Morrey-score of 86 was achieved. Complications could be shown in 2/8 patients. CONCLUSION: Both the treatment provides a clear individual benefit for the patients and predict promising results for the treatment of comminuted radial head fractures.

Options and limits of angle stable plates in the treatment of comminuted radial head fractures.

OBJECTIVE: New angle-stable plates provide more stability and better anatomical fit than previous plates. METHODS: 22 patients treated with an angle-stable plate were included. Postoperative the outcomes were evaluated according to the scoring systems of Morrey, Radin and Riseborough. RESULTS: 3 patients received a score of excellent, 14 good, and 5 satisfactory. We detected 3 cases of implant failure and 2 cases of postoperative neurological damage. 3 patientes received a radial head necrosis. CONCLUSIONS: Our results show that the angle-stable radial head locking plate can only be used in limited cases in the treatment of multi-fragment radial head fractures.

Evaluation of matrix metalloproteases as early biomarkers for bone regeneration during the applied Masquelet therapy for non-unions.

INTRODUCTION: In the current study, we sought to determine if serum concentrations of MMPs correlate with bone regeneration occurring during the course of the Masquelet-therapy and to identify if MMPs may serve as early biomarkers reflecting successful bone regeneration and tissue remodeling. MATERIAL AND METHODS: This study was designed as a prospective clinical observer study. We compared serum samples over the time of treatment, as a matched-pair analysis, from 10 patients who were treated successfully with the Masquelet-therapy (Responder) with 10 patients who did not respond to the Masquelet-therapy (Non-Responder). The quantitative measurement was performed with Luminex Performance Human High Sensitivity Assays according to manufacturer's instructions. The lab technician performing the Luminex assays was blinded to both patient data and clinical outcome. RESULTS: Analysis of the expression pattern of MMP-2, -8 and -9 showed significant differences between groups. Two days after the first step of the Masquelet therapy Responder showed peak values of MMP-8 and MMP-9 that where significantly higher (p = 0.003 and p = 0.042, respectively) than in Non-Responder. In contrast serum levels of MMP-2 were lower after the first step of the Masquelet therapy in the Non-Responder group. The ratio of MMP-9 and MMP-2 was significantly higher in the Responder group two days after step I (p = 0.031) as well as 4 weeks after step II (p = 0.030). CONCLUSION: The findings of the current study emphasize the potential role of MMPs as biomarkers in bone remodeling. In particular, a distinct expression of MMP-2 correlates with successful bone regeneration, whereas initial overexpression of MMP-2 serum levels might identify patients that have a higher risk for a poor outcome of the Masquelet-therapy. Furthermore, we were able to introduce the serum analysis of the ratio of MMP-9 and MMP-2 as promising novel modality for early prediction of the outcome of the Masquelet therapy. Further analysis of this ratio over time subsequent to the second step might serve as an early indicator of a favorable response to the induced membrane technique.

Combining advantages: Direct correlation of two-dimensional microcomputed tomography datasets onto histomorphometric slides to quantify three-dimensional bone volume in scaffolds.

Microcomputed tomography (mCT) belongs to the most powerful tools for the three-dimensional (3D) assessment of bone. While it is possible to refer to landmarks in mCT scans of actual bone structure, the assessment of calcified osteoid within scaffolds is problematic, due to the missing morphological correlates. Therefore, bone formation within scaffolds is mostly analyzed using indirect parameters such as changes in volume or surface alteration, preserving histomorphometry the gold standard in the direct analysis of bone formation. The presented method combines the advantages of mCT and histomorphometry: by creating an overlay image of the exact same histomorphometric and mCT slice, a grey-value-threshold representing calcified tissue was defined. Compared to the scaffolds global threshold, a direct evaluation of bone formation within scaffolds is possible by mCT-applied on the whole dataset, evaluation of bone volume is achievable. Two groups of human mesenchymal-stem-cell-seeded ß-Tricalciumphosphate-scaffolds were analyzed: whilst group B was stimulated with 0.1 µg/mL Bone Morphogenetic Protein-7, group A remained unstimulated during in vivo differentiation. Strong correlations (r > 0.8) were obtained between percentage bone area in mCT and histomorphometry, as well as for 3D bone volume. Using the presented method, 3D bone volume can be directly estimated within scaffolds by combination of histomorphometric and mCT-analysis. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1812-1821, 2018.

Clinical experiences in the use of a gentamicin-coated titanium nail in tibia fractures.

Despite the improvement of surgical techniques surgical site infections (SSIs) still remain clinically challenging in high risk patients undergoing osteosynthesis for tibia fractures. The use of an antibiotic coated implant might reduce the adhesion of bacteria on the implant surface and could therefore reduce the rate of implant-related infection or osteomyelitis. A gentamicin-coated tibia nail was evaluated in a prospective study. Four centers enrolled 100 patients (99 treated) with fresh open or closed tibia fractures, or for non-union revision surgery and followed them for 18 months. Data collected included infection events, radiographs, SF-12, EQ-5D, Iowa Ankle score, and the WOMAC questionnaire. Sixty-eight of the 99 treated patients suffered from a fresh fracture, while in 31 patients, the intramedullary nail was implanted for revision purposes, including non-unions due to infection. Fifteen (22%) of the fresh fractures were GA Type III. The follow-up rate was 87% and 82% at 12 months and 18 months, respectively. Deep surgical site infections occurred in 3 fresh fractures and two in revision surgeries. We did not observe any local or systemic toxic effects related to gentamicin during this study. The use of the antibiotic coated nail is an option in patients with a high infection risk, like open factures or infected non unions, in the prevention of the onset of an implant-related infection or osteomyelitis.

CCL-2 as a possible early marker for remission after traumatic spinal cord injury.

STUDY DESIGN: Prospective observational study. OBJECTIVES: To describe the correlation between CCL-2, CCL-3, CCL-4 and CXCL-5 serum levels and remission after traumatic spinal cord injury (SCI) in a human protocol compared with animal studies. SETTING: Germany, Rhineland-Palatinate (Rheinland-Pfalz). METHODS: We examined the serum levels of CCL-2, CCL-3, CCL-4 and CXCL-5 over a 12-week period; in particular, at admission and 4, 9 and 12 h, 1 and 3 days and 1, 2, 4, 8 and 12 weeks after trauma. According to our study design, we matched 10 patients with TSCI and neurological remission with 10 patients with an initial ASIA A grade and no neurological remission. In all, 10 patients with vertebral fracture without neurological deficits served as control. Our analysis was performed using a Luminex Cytokine Panel. Multivariate logistic regression models were used to examine the predictive value with respect to neurological remission vs no neurological remission. RESULTS: The results of our study showed differences in the serum expression patterns of CCL-2 in association with the neurological remission (CCL-2 at admission P=0.013). Serum levels of CCL-2 and CCL-4 were significantly different in patients with and without neurological remission. The favored predictive model resulted in an area under the curve (AUC) of 93.1% in the receiver operating characteristic (ROC) analysis. CONCLUSIONS: Our results indicate that peripheral serum analysis is a suitable concept for predicting the patient's potential for neurological remission after TSCI. Furthermore, the initial CCL-2 concentration provides an additional predictive value compared with the NLI (neurological level of injury). Therefore, the present study introduces a promising approach for future monitoring concepts and tracking techniques for current therapies. The results indicate that future investigations with an enlarged sample size are needed in order to develop monitoring, prognostic and scoring systems.

[Tibial defects and infected non-unions : Treatment results after Masquelet technique]. / Tibiadefekt- und Infektpseudarthrosen : Behandlungsergebnisse nach Masquelet-Technik.

BACKGROUND: The treatment of non-unions with large bone defects or osteitis is a major challenge in orthopedic and trauma surgery. A new concept of therapy is a two-step procedure: Masquelet technique according to the diamond concept. METHODS: Between February 2010 and June 2014, 55 patients with tibia non-unions or infections were treated in a two-step Masquelet technique in our center. The patients' average age was 48 (median 50; minimum 15-maximum 72) with an average BMI (body mass index) of 28 (27; 18-52). There were 10 (18 %) female and 45 (82 %) male patients in the group. All study patients went through a follow up. Bone healing and clinical functional data were collected, as well as data according to subjective patient statements about pain and everyday limitations. RESULTS: In 42 cases (76.4 %) the outcome was a sufficient bony consolidation. On average, the time to heal was 10.3 (8, 5; 3-40) months, defect gaps were 4 cm (3 cm; 0,6-26 cm), and on average the patients had had 6 (median 4; range 1-31) previous operations . In all cases patients received osteosynthesis as well as a defect filling with RIA (reamer-irrigator-aspirator), and growth factor BMP-7 (bone morphogenetic protein-7). In 13 cases (23.6 %) there was no therapeutic success. In the evaluation of the SF12 questionnaire the mental health score increased from 47.4 (49.1; 27.6-65.7) to 49.8 (53.0; 28.7-69.4) and the well-being score from 32.7 (32.7;16.9-55.7) to 36.6 (36.5; 24.6-55.9). CONCLUSION: The two-step bone grafting method in the Masquelet technique used for tibia non-unions according to the diamond concept is a promising treatment option. Its application for tibia shaft non-unions with large bone defects or infections means a high degree of safety for the patient.

Immunological characterization of the early human fracture hematoma.

The initial inflammatory phase of fracture healing is of great importance for the clinical outcome. We aimed to develop a detailed time-dependent analysis of the initial fracture hematoma. We analyzed the composition of immune cell subpopulations by flow cytometry and the concentration of cytokines and chemokines by bioplex in 42 samples from human fractures of long bones <72 h post-trauma. The early human fracture hematoma is characterized by maturation of granulocytes and migration of monocytes/macrophages and hematopoietic stem cells. Both T helper cells and cytotoxic T cells proliferate within the fracture hematoma and/or migrate to the fracture site. Humoral immunity characteristics comprise high concentration of pro-inflammatory cytokines such as IL-6, IL-8, IFNγ and TNFα, but also elevated concentration of anti-inflammatory cytokines, e.g., IL-1 receptor antagonist and IL-10. Furthermore, we found that cells of the fracture hematoma represent a source for key chemokines. Even under the bioenergetically restricted conditions that exist in the initial fracture hematoma, immune cells are not only present, but also survive, mature, function and migrate. They secrete a cytokine/chemokine cocktail that contributes to the onset of regeneration. We hypothesize that this specific microenvironment of the initial fracture hematoma is among the crucial factors that determine fracture healing.

In vivo quantification of gentamicin released from an implant coating.

Drug-releasing implants are gaining increasing interest. The present study reports a detailed physicochemical analysis of a polymeric coating based on poly(D,L-lactide) and the incorporated gentamicin combined with an in vitro and in vivo study of the gentamicin release. Differential scanning calorimeter, Fourier transform infrared spectroscopy, gel permeation chromatography and high-performance liquid chromatography showed no effect of the gamma sterilisation on the coating components or an interaction of the polymer and the gentamicin. Microbiological analysis revealed an inhibition of bacterial growth on the implant surface. For the in vivo study, gentamicin-coated wires were implanted into the tibiae of rats and harvested at different time points up to day 42. To monitor the release in vivo, gentamicin was quantified in serum, bone, endosteum, kidney, and on the explanted wires. Gentamicin was detectable over a time period of 42 days in the endosteum, up to seven days in the kidney, up to 4 h in the bone and at the end of the experiment on one of eight wires. The locally released gentamicin caused no histological changes of the kidney. Microbiologically active concentrations of released gentamicin were found in the endosteum up to 4 h after implantation. The combination of different methods supports the individual results, where quantification is complemented by visualisation or antimicrobial activity. This work demonstrates that the coating procedure results in no substantial alteration of the incorporated drug and that the in vitro burst release occurs also in vivo.

Treatment of nonunions in fractures of the humeral shaft according to the Diamond Concept.

METHODS: Between 2005 and 2012, 50 patients (23 female, 27 male) with nonunion of the humeral shaft were included in this retrospective study. The mean age was 51.3 years (14 to 88). The patients had a mean of 1.5 prior operations (sd 1.2;1 to 8). All patients were assessed according to a specific risk score in order to devise an optimal and individual therapy plan consistent with the Diamond Concept. In 32 cases (64%), a change in the osteosynthesis to an angular stable locking compression plate was performed. According to the individual risk an additional bone graft and/or bone morphogenetic protein-7 (BMP-7) were applied. RESULTS: A successful consolidation of the nonunion was observed in 37 cases (80.4%) with a median healing time of six months (IQR 6). Younger patients showed significantly better consolidation. Four patients were lost to follow-up. Revision was necessary in a total of eight (16%) cases. In the initial treatment, intramedullary nailing was most common. DISCUSSION: The use of locking compression plates in combination with autologous cancellous bone graft has been shown to be a safe and effective treatment. In more complex cases, the use of the Masquelet technique and BMP-7 may be indicated at the first revision operation. TAKE HOME MESSAGE: Our results suggest the Diamond Concept is a successful treatment strategy for nonunions of the humeral shaft.

[Long Bone Nonunion]. / Pseudarthrosen langer Röhrenknochen.

The percentage of delayed or non-unions after fractures of long bones depends on the individual risk profile at approximately 10 %. The current definition states that a non-union is a fracture that will not consolidate without any further intervention - independent from the treatment time. At the early stage of a non-union a conservative treatment is possible in case of an adequately stable situation. The operative treatment depends on the type of the non-union. There are one-step or two-step procedures, all according to the principles of the "diamond concept". This means improvement of the mechanical situation - in most cases by means of a reosteosynthesis - and vascularization, local application of osteoconductive carriers e.g. tricalciumphosphate, vital cells from autologous bone and osteoinductive substances like bone morphogenetic proteins (BMP-2 or BMP-7). Hypertrophic and atrophic non-unions without large defect gaps or signs of infection can be treated with a one-step procedure. For treating infected non-unions or non-unions with large defect gaps the Masquelet technique is recommended.

[E-learning in orthopedics and traumatology. A comparative pilot study on acceptance and knowledge acquisition among users and non-users]. / E-Learning in der Orthopädie und Unfallchirurgie : Eine vergleichende Pilotstudie zur Akzeptanz und zum Wissenszuwachs unter Nutzern und Nichtnutzern.

BACKGROUND: Additional internet-based learning tools (e-learning) are successfully used in the curricula of many disciplines and are highly accepted among students. However, in orthopedics and traumatology e-learning is underrepresented and scientific papers are rare. The aim of the present pilot study was to evaluate the acceptance of the e-learning module network for students in traumatology and orthopedics (NESTOR) among users and non-users and to analyze the effect of this additional learning tool on knowledge acquisition. MATERIAL AND METHODS: A total of 544 students were asked to complete evaluation questionnaires at the end of two semesters using different ones for NESTOR users and non-users. The gain of knowledge was analyzed by two written knowledge tests (pre-post test, 20 multiple choice questions) at the beginning and end of the semester comparing these two groups. RESULTS: A total of 191 students took part in the evaluation and 152 completed both written tests. The NESTOR users showed a high acceptance of the e-learning system and non-users considered e-learning beneficial as well. Reasons given for not using NESTOR were lack of time, lack of information about the existence of NESTOR and a lack of interest in this discipline and e-learning in general. Both groups significantly increased their level of knowledge during the course of the semester (p < 0.01), whereas users scored significantly higher in the post-test (p < 0.05). CONCLUSION: The presented data support the high acceptance among users and the benefit of the e-learning project NESTOR in teaching students in orthopedics and traumatology. Based on experience and these results the permanent implementation of an additional e-learning module in the curriculum can be recommended for other faculties. In this process the critical comments of the non-users determined in the present study should be addressed.

[Treatment of Mason type II radial head fractures by percutaneous reduction]. / Die Behandlung von Radiusköpfchenfrakturen Typ Mason II durch perkutane Drahtreposition.

BACKGROUND: The therapeutic algorithm for the treatment of Mason type II radial head fractures is still controversially discussed. This study describes the technique of percutaneous fracture reduction without additional internal fixation of the radial head as an alternative to open reduction and presents the results of the method. MATERIAL AND METHODS: The data from 26 out of 30 patients with a Mason type II radial head fracture who had been consecutively treated with percutaneous fracture reduction were evaluated retrospectively. The analysis comprised the disabilities of shoulder and hand (DASH) score, the Mayo elbow performance score (MEPS) and data from the radiological examinations. RESULTS: The average follow-up time was 21 months (range 6-47 months). In 22 cases (85 %) an anatomical reduction could be achieved, 2 cases (8 %) showed a complete redislocation of the fragment and 2 cases (8 %) a partial redislocation. The average DASH score was 5.6 points (range 0-56) and the average MEPS was 93.8 (range 60-100). Only 4 patients (15 %) reported persisting functional impairment with a DASH score >10. CONCLUSIONS: The method of percutaneous reduction of radial head fractures without additional internal fixation in Mason type II fractures has been demonstrated to be a good alternative to open reduction.

Local gentamicin application does not interfere with bone healing in a rat model.

For the prophylaxis and treatment of bony infections antibiotics are locally used. Since several decades antibiotics mixed with bone cement (methylmethacrylate) are successfully used in prosthetic surgery and a gentamicin coated tibial nail is approved in Europe for fracture stabilization. The goal of the present study was to investigate if gentamicin, locally applied from a polymeric coating of intramedullary nails, might interfere with the bone healing process. Female Sprague Dawley rats (n = 72) were used and the tibiae were intramedullary stabilized with Kirschner-wires (k-wires) after osteotomy. This model was established earlier and shows a delayed healing with a prolonged inflammatory reaction. The open approach is clinically more relevant compared to a closed one because it mimics the clinically critical case of an open fracture, which has a higher risk of infection. The k-wire was either coated with the polymer poly(d,l-lactide) (control group) or with 10% gentamicin incorporated into the polymer (gentamicin group). In vivo µCT analyses were performed at days 10, 28, 42, and 84 after osteotomy. Mechanical torsional testing and histological evaluation were done at the days of sacrifice: 28, 42, and 84. The µCT analyses revealed an increase in tissue mineral density (TMD) over the healing period in both groups. In the control group, the torsional stiffness and maximum load did not reach the values of the intact contralateral side at any time point. At day 84 the gentamicin treated tibiae, however, showed significantly better maximum load compared to the control group. The histology showed no bony bridging in the control, whereas in 2 of 5 calluses of the gentamicin group mineralized bridging occurred. Significantly more mineralized tissue was measured in the gentamicin group. This study shows that the local gentamicin application does not negatively interfere with the long term healing process. Local infection prophylaxis is effective without negative effects on bone healing.

Increase in soluble CD95L during subacute phases after human spinal cord injury: a potential therapeutic target.

STUDY DESIGN: A pilot study measuring the levels of serum-soluble CD95 ligand (CD95L) in eight spinal cord-injured patients. OBJECTIVES: To determine the soluble concentration of CD95L in spinal cord injury (SCI) patients after trauma. METHODS: We collected blood samples from eight patients with acute traumatic SCI. Soluble CD95L serum levels were determined using an enzyme-linked immunosorbent assay. American Spinal Injury Association (ASIA) was determined according to ASIA classification. The patients were monitored, and venous blood was drawn after arrival at the hospital on the 1st and 3rd day and during the 1st, 2nd, 4th, 8th and 12th weeks after trauma. RESULTS: The average patient age was 48.1 years (18-86 years). Three patients were paraplegic (two incomplete, one complete), five were quadriplegic (one complete, four incomplete). The serum concentration of soluble CD95L (sCD95L) decreased during the 1st week (41 ng(- l)) and increased after the 2nd week in all eight patients. It peaked during the 4th week (68.5 ng (- l)) and reached a plateau during the 12th week (76.2 ng (- l)). There are many possible explanations for not being able to detect a statistical significance, one of course being the small sample size. CONCLUSION: Promising results for anti-CD95L therapy have already been documented in lab studies with rodents. Anti-CD95L blocks the pro-apoptotic and proinflammatory activity of membrane-bound CD95L during the acute phase of SCI. We observed that sCD95L levels are elevated during the subacute and intermediate phases of SCI. It would be of great interest to study a larger group of patients to determine whether higher sCD95 levels are correlated with improved or impaired neurological outcome or with increasing levels of autoimmune components in peripheral blood.