Prospective Comparison of a Metal-Free Ceramic Total Knee Arthroplasty with an Identical Metal System.

AIMS: The aim of this open-label, prospective, short-term study was to carry out an initial comparison of a completely metal-free ceramic with a geometrically identical metallic arthroplasty over a 1-year follow-up period. METHODS: This study investigates a completely metal-free system using a composite matrix material containing aluminum oxide (Al2O3, BPK-S Integration, Peter Brehm GmbH, Weisendorf, Germany) or zirconium oxide (ZrO2, BPK-S Integration Ceramic, Biolox Delta-CeramTec GmbH, Plochingen, Germany). Eighty patients (40 in each group) received either a completely metal-free ceramic system (matrix of aluminum and zirconium oxide) or an anatomically identical metallic knee system made of a cobalt-chromium alloy. Clinical assessment was performed preoperatively, and during follow-up at 3 and 12 months, using the Knee Society Score, Oxford Knee Score, and EQ-5D-VAS. For radiological evaluation, standard preoperative and postoperative standardized radiographs were taken at the given follow-up visits. RESULTS: The postoperative clinical scores improved significantly at the 3- and 12-month follow-ups, but did not differ statistically between the two groups. The radiologically evaluated mean postoperative mechanical and anatomical axes showed proper alignment within both groups at all times. No revision surgery had to be performed, and no complications or loosening were recorded whatsoever. CONCLUSIONS: To our knowledge, this is the first study comparing a total ceramic metal-free knee system with a geometrically identical metallic TKA (total knee arthroplasty). Longer follow-ups will be required to demonstrate the overall efficiency of this TKR and perhaps to expand its medical indication.

The Operative Management of Flail Chest Injuries with Concomitant Sternal Fracture.

Background: Flail Chest Injuries (FCI) are one of the most severe thoracic injuries. Moreover, an additional sternal fracture (SF) even worsens the outcome, such as the duration of mechanical ventilation, therefore an surgical fixation of the fractures could be considered in certain cases to improve the weaning from the ventilator. This paper aims to emphasize on the management of different types of SF in FCI. Methods: All surgically treated cases (2012-2016) that showed the combination of FCI and SF have been evaluated for their clinical details, the morphology of the fractures and the technical aspects of the surgical procedure in a retrospective investigation. Results: All of the SF (n=15) had been fixed by locked plate osteosynthesis through a median approach in a supine position. Three main regions of the sternum showed the need for different fixation strategies: the upper manubrium, central and lower corpus sterni. Concomitant rib fractures were addressed either through the same approach or through additional limited incisions. Conclusions: Combinations of SF and FCI are high risc injuries with high demand on surgical skills. They can be properly fixed with a locking plate osteosynthesis through a combination of limited incisions employing different types of plates depending on the type of SF.

Antibacterial Effect of a 4x Cu-TiO2 Coating Simulating Acute Periprosthetic Infection-An Animal Model.

The purpose of our study was to investigate the antibacterial effect of a spacer (Ti6Al4V) coated with 4x Cu-TiO2 in an animal model simulating an acute periprosthetic infection by Staphylococcus aureus. Ti6Al4 bolts contaminated with Staphylococcus aureus were implanted into the femoral condyle of rabbits (n = 36) divided into 3 groups. After one week in group 1 (control) the bolts were removed without any replacement. In group2 Ti6Al4V bolts with a 4x Cu-TiO2 coating and in group 3 beads of a gentamicin-PMMA chain were imbedded into the borehole. Microbiological investigation was performed at the primary surgery, at the revision surgery and after scarification of the rabbits 3 weeks after the first surgery. Blood tests were conducted weekly. The initial overall infection rate was 88.9%. In group 2 and 3 a significant decrease of the infection rate was shown in contrast to the control group. The C-reactive protein (CRP) levels declined one week after the first surgery except in the control group where the CRP level even increased. This is the first in vivo study that demonstrated the antibacterial effects of a fourfold Cu-TiO2 coating. For the future, the coating investigated could be a promising option in the treatment of implant-associated infections.

Concomitant Sternal Fracture in Flail Chest: An Analysis of 21,741 Polytrauma Patients from the TraumaRegister DGU®.

Background Isolated sternal fractures (SFs) rarely show complications, but their influence in a thorax trauma of the seriously injured still remains unclear. Methods A retrospective analysis of the TraumaRegister DGU® was performed involving the years 2009 to 2013 (Injury Severity Score [ISS] ≥ 16, primary admission to a trauma center). Cohort formation: Unilateral and bilateral flail chest (FC) injuries with and without a concomitant SF, respectively. Results In total, 21,741 patients (25% female) met the inclusion criteria, with 3,492 (16.1%) showing SF. Unilateral FC patients were on average 53.6 ± 18.4 years old, and bilateral FC patients were on average 55.2 ± 17.7 years old. The ISS in unilateral FC and bilateral FC amounted to 31.2 ± 13.0 and 43.4 ± 13.1 points, respectively. FC with an SF occurred more frequently as an injury to car occupants and less frequently as an injury to motorcyclists or in injuries due to falls. Conclusion Patients with an SF additional to an FC had longer hospital and intensive care unit stays and were longer artificially respirated than those patients without an SF. SF indicates possible cardiac and thoracic spine injuries.

The oblique fracture of the manubrium sterni caused by a seatbelt--a rare injury? Treatment options based on the experiences gained in a level I trauma centre.

INTRODUCTION: Sternal fractures are rare with 3-8 % out of the total number of trauma cases mostly caused by direct impact to the anterior chest wall. Most cases described are due to motor vehicle crash either caused by direct impact to the steering wheel or by the seat belt. Fractures mainly occur to the sternal body. Only rarely are cases of manubrium fractures described in literature, for example, in relationship with a direct impact to the shoulder which caused an oblique fracture near to the sternoclavicular joint. Three patients with profoundly dislocated oblique manubrium fracture were admitted to our Level I Trauma Center in 2012 and 2013. Those patients suffered from instability of the upper sternum and the shoulder girdle. MATERIAL AND METHODS: Between January 2012 and October 2013, a total of 538 trauma patients were admitted to the emergency room and received whole body CT-scan. They were analysed retrospectively for sternal fractures. In cases of instability and dislocation, fracture stabilisation was performed by anterior plating through a medial approach using low profile titanium plates (MatrixRib®). RESULTS: Seventy-nine (14.7 %) patients showed sternal fracture, out of which 13 (2.4 %) patients showed a fracture of manubrium, ten caused by seatbelt. In three cases stabilization was performed. Follow up showed sufficient consolidation without complications. DISCUSSION: A total of 16.5 % of sternal fractures were localized at the manubrium, mostly caused by seat belt. Fractures without significant dislocation seemed to be stable and healed well under conservative treatment. Dislocation in this region leads to unstable shoulder girdle. Anterior plating provides sufficient stabilisation and allowed consolidation.

Surgical fixation of sternal fractures: preoperative planning and a safe surgical technique using locked titanium plates and depth limited drilling.

Different ways to stabilize a sternal fracture are described in literature. Respecting different mechanisms of trauma such as the direct impact to the anterior chest wall or the flexion-compression injury of the trunk, there is a need to retain each sternal fragment in the correct position while neutralizing shearing forces to the sternum. Anterior sternal plating provides the best stability and is therefore increasingly used in most cases. However, many surgeons are reluctant to perform sternal osteosynthesis due to possible complications such as difficulties in preoperative planning, severe injuries to mediastinal organs, or failure of the performed method. This manuscript describes one possible safe way to stabilize different types of sternal fractures in a step by step guidance for anterior sternal plating using low profile locking titanium plates. Before surgical treatment, a detailed survey of the patient and a three dimensional reconstructed computed tomography is taken out to get detailed information of the fracture's morphology. The surgical approach is usually a midline incision. Its position can be described by measuring the distance from upper sternal edge to the fracture and its length can be approximated by the summation of 60 mm for the basis incision, the thickness of presternal soft tissue and the greatest distance between the fragments in case of multiple fractures. Performing subperiosteal dissection along the sternum while reducing the fracture, using depth limited drilling, and fixing the plates prevents injuries to mediastinal organs and vessels. Transverse fractures and oblique fractures at the corpus sterni are plated longitudinally, whereas oblique fractures of manubrium, sternocostal separation and any longitudinally fracture needs to be stabilized by a transverse plate from rib to sternum to rib. Usually the high convenience of a patient is seen during follow up as well as a precise reconstruction of the sternal morphology.

Elastic Stable Chest Repair as a Means of Stabilizing the Anterior Chest Wall in Recurrent Pectus Excavatum with Sternocostal Pseudarthrosis: An Innovative Fixation Device.

INTRODUCTION: Open surgical procedures in the treatment of pectus excavatum (PE) involve predetermined incisions in the parasternal cartilage and the bony ribs. For some procedures, the ribs are even dissected from the sternum for better sternal mobilization and thus better elevation of the funnel. Secure restoration of the sternocostal junction is then required, with the consequence that healing may be quite impaired. Patients may also subsequently suffer from sternocostal nonunion, for example, pseudarthrosis, and dislocated ribs, as well as pain and a recurrence of PE. MATERIALS AND METHODS: Patients underwent another open surgery with revision of the pseudarthrotic sternocostal junctions and sufficient mobilization of the anterior chest wall, followed by an open reduction and internal fixation using Matrix Rib titanium plates (Synthes, Oberdorf, Switzerland). This procedure consisted of elevating the anterior chest wall and fixing the ribs to the sternum. In 2011 and 2012, we studied this procedure, known as elastic stable chest repair (ESCR), in a series of 20 patients. The patients underwent clinical and ultrasound examinations and X-ray radiographs after the operation, after 6 weeks, and at 3- and 12-month intervals. RESULTS: Follow-up showed high patient tolerance, although a loose plate was observed in one patient and a broken plate in three patients. A stable union was achieved for all sternocostal pseudarthroses. PE improved highly significantly (p < 0.001), as the Haller index decreased from 3.6 (range: 2.7-6.6, standard deviation [SD]: 0.92) to 2.7 (range: 2.0-3.7, SD: 0.42). Pain in the anterior chest wall was significantly reduced after the operation in the majority of cases. All but one patient was mobilized already the day after the operation. CONCLUSIONS: ESCR in recurrent PE achieved functional stabilization of the anterior chest wall combined with satisfactory results.

Surgical fixation of sternal fractures: locked plate fixation by low-profile titanium plates--surgical safety through depth limited drilling.

PURPOSE: Operative treatment of sternal fractures has become a matter of increasing interest. Anterior plating seems to be the most appropriate method for fixing sternal fractures. However, there are several concerns in relation to the operative procedure such as severe injuries to mediastinal organs, patient comfort and proper stabilisation, for example. This paper describes a safe method of anterior sternal plating using locked plate fixation with limited depth drilling. METHODS: Ten patients with sternal fractures were included in this cohort study and were treated by anterior plating using one or two plates in parallel through a median approach to the sternum. Follow up was performed after six weeks, 12 weeks and six months. RESULTS: Follow up revealed no serious complications. One patient suffered from postoperative wound seroma. No problems were caused by the plates. CONCLUSIONS: Sternal plating using low profile locked titanium plates seems to be a safe and stable method with a high level of patient comfort.

Release of Cu2+ from a copper-filled TiO2 coating in a rabbit model for total knee arthroplasty.

The aim of this study was the investigation of a copper-filled TiO2 coating, that in vitro showed good antibacterial properties combined with good tissue tolerance in an animal model. To better understand the antibacterial mechanism of the bioactive coating the release of copper (Cu) ions over time was monitored to be able to detect possible threats as well as possible fields of application. 30 New Zealand White rabbits were divided into two groups with 15 animals per group. In group 1 (control group) Ti6Al4 V bolts were implanted into the distal femur, in group 2 the Ti6Al4 V bolts were coated with four TiO2-coatings with integrated Cu(2+)-ions (4 × Cu-TiO2). Blood tests were performed weekly until the animals were sacrificed 4 weeks postoperative. The maximum peak of Cu and ceruloplasmin concentration could be seen in both groups one week postoperative, whereas the Cu values in group II were significantly higher. The Cu concentration in both groups approximated the initial basic values 4 weeks postoperative. The 4 × Cu-TiO2 coating tested in our rabbit model for total knee arthroplasty is an active coating that releases potentially antibacterial Cu(2+) for 4 weeks with a peak 1 week postoperative. The bioactive coating could be a promising approach for a use in the field of implant related infection, orthopaedic revision and tumor surgery in the future.

Low incidence of oncogenic EGFR, HRAS, and KRAS mutations in seborrheic keratosis.

Seborrheic keratosis (SK) represents a frequent epidermal skin tumor. Although lacking a malignant potential, these tumors reveal multiple oncogenic mutations. A previous study identified activating mutations in 89% of SK, particularly in FGFR3 and PIK3CA genes. The aim of this study was to identify further oncogenic mutations in human SK. Therefore, we screened for mutations in EGFR, FGFR2, PIK3R1, HRAS, KRAS, and NRAS genes using both Sanger sequencing of selected exons and a multiplex SNaPshot assay in 58 SK of 14 patients. We identified a somatic EGFR p.L858R mutation in 1 SK. Furthermore, the HRAS mutations p.G13R (2/58 SK) and p.Q61L (2/58 SK) were found. These mutations have not been described in human SK yet. In addition, 1 SK revealed the KRAS p.G12V mutation, which has already been reported in SK. No mutations were detected in FGFR2, PIK3R1, and NRAS genes. The results of this study suggest that activating mutations of EGFR, HRAS, and KRAS contribute to the pathogenesis of human SK, although at a lower frequency than FGFR3 and PIK3CA mutations. FGFR2, PIK3R1, and NRAS mutations obviously do not have a significant role in the development of SK.

Impact of different coils on biochemical T2 and T2* relaxation time mapping of articular patella cartilage.

OBJECTIVE: The purpose of our study was to assess T2 and T2* relaxation time values of patella cartilage in healthy volunteers using three different coils at 3.0 Tesla MRI and their influence on the quantitative values. METHODS: Fifteen volunteers were examined on the same 3-Tesla MR unit using three different coils: (i) a dedicated eight-channel knee phased-array coil; (ii) an eight-channel multi-purpose coil, and (iii) a one-channel 1H surface coil. T2 and T2* relaxation time measurements were prepared by a multi-echo spinecho respectively a gradient-echo sequence. A semi-automatic region-of-interest analysis was performed for patella cartilage. To allow stratification, a subregional analysis was carried out (deep-superficial cartilage layer). Statistical analysis-of-variance was performed. RESULTS: The mean quantitative T2 values showed statistically significant differences in all comparison combinations. The differences between the mean quantitative T2* values were slightly less pronounced than the T2 evaluation and only the comparison between (i) and (ii) showed a significant difference. The results of T2 and T2* values showed, independent of the used coil, higher values in the superficial zone compared to the deep zone (p < 0.05). Looking at the signal alterations, all coils showed clearly higher values (and thus more signal alterations as a sign of noise) in the deep layer. The validation of the reliability showed a high intra-class correlation coefficient and hence a very high plausibility (ICC was between 0.870 and 0.905 for T2 mapping and between 0.879 and 0.888 for T2* mapping). CONCLUSIONS: The present results demonstrate that biochemical T2 and T2* mapping is significantly dependent on the utilized coil.

Keratinocytic epidermal nevi are associated with mosaic RAS mutations.

BACKGROUND: Activating RAS mutations in the germline cause rare developmental disorders such as Costello syndrome. Somatic RAS mutations are found in approximately 30% of human cancers. Keratinocytic epidermal nevi (KEN) represent benign congenital skin lesions arranged along Blaschko's lines. A subgroup of KEN is caused by hotspot oncogenic FGFR3 and PIK3CA mutations in mosaicism, but the majority lack these mutations. METHODS: This study screened 72 KEN for activating mutations in RAS genes and other oncogenes. RESULTS: Activating RAS mutations were identified in 28/72 (39%) of KEN. HRAS was the most commonly affected oncogene (86%), with the HRAS p.G13R substitution representing a new hotspot mutation. CONCLUSION: These results indicate that activating RAS somatic mutations leading to mosaicism result in benign KEN of the skin. Given the prevalence of KEN, mosaic HRAS mutations appear to be more common in patients than germline ones. These findings identify KEN as a mosaic RASopathy and lend further support to the notion that genetic mosaicism is an important contributor to disease.

Morphological and biochemical T2 evaluation of cartilage repair tissue based on a hybrid double echo at steady state (DESS-T2d) approach.

PURPOSE: To use a new approach which provides, based on the widely used three-dimensional double-echo steady-state (DESS) sequence, in addition to the morphological information, the generation of biochemical T2 maps in one hybrid sequence. MATERIALS AND METHODS: In 50 consecutive MRIs at 3.0 Tesla (T) after matrix-associated autologous chondrocyte transplantation (MACT) of the knee, by the use this new DESS-T2d approach, the morphological Magnetic resonance Observation of CArtilage Repair Tissue (MOCART) score, as well as biochemical T2d values were assessed. Furthermore, these results were correlated to standard morphological sequences as well as to standard multi-echo spin-echo T2 mapping. RESULTS: The MOCART score correlated (Pearson:0.945; P < 0.001) significantly as assessed with standard morphological sequences (68.8 ± 13.2) and the morphological images of the DESS T2d sequence (68.7 ± 12.6). T2 and T2d relaxation times (ms) were comparable in between the control cartilage (T2: 52.5 ± 11.4; T2d: 46.6 ± 10.3) and the repair tissue (T2: 54.4 ± 11.4; T2d: 47.5 ± 13.0) (T2: P = 0.157; T2d: P = 0.589). As expected, T2d values were lower than the standard-T2 values, however, both functional relaxation times correlated significantly (Pearson:0.429; P < 0.001). CONCLUSION: The presented hybrid approach provides the possibility to combine morphological and biochemical MRI in one fast 3D sequence, and thus, may attract for the clinical use of biochemical MRI.

Low incidence of EGFR and HRAS mutations in cutaneous squamous cell carcinomas of a German cohort.

Epidermal growth factor receptor (EGFR) is highly expressed in squamous cell carcinoma (SCC). The response of patients with lung cancer to EGFR inhibitors is significantly associated with the presence of EGFR mutations. Although these drugs have already been used for the treatment of advanced cutaneous SCC, the knowledge about EGFR mutations in this cancer is limited to one previous study in the US population. We analysed the presence of EGFR and concomitant HRAS mutations in a German cohort of 31 patients with cutaneous SCC by direct sequencing of EGFR and SNaPshot analysis of concomitant RAS mutations. We found a low prevalence of EGFR mutations (1/31; 3%) and HRAS mutations (1/31; 3%). The detected P741L EGFR mutation was proven to be somatic. Our results indicate that both EGFR and HRAS mutations are rare events in the carcinogenesis of cutaneous SCC, and therefore, only a small subgroup of patients will benefit from the screening for EGFR mutations in the run-up to targeted therapies with EGFR inhibitors.

Identification of new genes associated with melanoma.

PURPOSE: Repeated failures in melanoma therapy made clear that the molecular mechanisms leading to melanoma are still poorly understood. In this study, we aim to provide a more comprehensive understanding of the transcriptional profiles and signalling pathways associated with melanoma. METHODS: Gene expression was analysed using the Affymetrix Human Genome U133A 2.0 GeneChip arrays. To avoid culture artifacts, we used microdissected fresh frozen material of 18 melanocytic nevi (MN), 20 primary melanomas (PM) and 20 metastatic melanomas (MM). Statistical analysis was performed with Genomatix Chipinspector, Ingenuity™ Software, SPSS Software and Partek Genomic Suite 6.4. Expression levels of selected transcripts were verified by quantitative real-time RT-PCR and immunostaining of a tissue microarray sampling more than 280 cases of MN, PM and MM with known clinical outcome. RESULTS: A total of 284 differentially expressed genes was detected in PM compared with MN and 189 genes in MM compared with PM affecting common cancer pathways such as MAPK-, Wnt- and Notch-signalling. Using principal component analysis, the samples could be grouped according to their histological entity. We identified a panel of novel melanoma-associated markers: frizzled-related protein, an antagonist of Wnt; tranducin-like enhancer of split 1, a transcription factor partner of TCF/LEF-1; CNTN1, an activator of Notch signalling; two Serpin peptidase inhibitors, Serpin B3/B4 and the TGF-ß family member GDF15, the latter with association to MAPK-signalling.

Advanced morphological 3D magnetic resonance observation of cartilage repair tissue (MOCART) scoring using a new isotropic 3D proton-density, turbo spin echo sequence with variable flip angle distribution (PD-SPACE) compared to an isotropic 3D steady-state free precession sequence (True-FISP) and standard 2D sequences.

PURPOSE: To evaluate a new isotropic 3D proton-density, turbo-spin-echo sequence with variable flip-angle distribution (PD-SPACE) sequence compared to an isotropic 3D true-fast-imaging with steady-state-precession (True-FISP) sequence and 2D standard MR sequences with regard to the new 3D magnetic resonance observation of cartilage repair tissue (MOCART) score. MATERIALS AND METHODS: Sixty consecutive MR scans on 37 patients (age: 32.8 ± 7.9 years) after matrix-associated autologous chondrocyte transplantation (MACT) of the knee were prospectively included. The 3D MOCART score was assessed using the standard 2D sequences and the multiplanar-reconstruction (MPR) of both isotropic sequences. Statistical, Bonferroni-corrected correlation as well as subjective quality analysis were performed. RESULTS: The correlation of the different sequences was significant for the variables defect fill, cartilage interface, bone interface, surface, subchondral lamina, chondral osteophytes, and effusion (Pearson coefficients 0.514-0.865). Especially between the standard sequences and the 3D True-FISP sequence, the variables structure, signal intensity, subchondral bone, and bone marrow edema revealed lower, not significant, correlation values (0.242-0.383). Subjective quality was good for all sequences (P ≥ 0.05). Artifacts were most often visible on the 3D True-FISP sequence (P < 0.05). CONCLUSION: Different isotropic sequences can be used for the 3D evaluation of cartilage repair with the benefits of isotropic 3D MRI, MPR, and a significantly reduced scan time, where the 3D PD-SPACE sequence reveals the best results.

Generalized solar lentigines in a patient with a history of radon exposure.

A woman with generalized lentigines without associated non-cutaneous abnormalities is described. The patient showed brownish-pigmented flat or slightly elevated spots with a diameter of 1­5 mm. The histopathology of the lesions was compatible with a diagnosis of solar lentigines (SLs) or flat seborrhoeic keratosis. Unlike SLs, which develop typically on sun-damaged skin of the face, the dorsum of the hands and forearms, this patient showed the lentigines most prominently on the thighs and lower legs. Besides increased recreational UV exposure, the patient had a history of occupational radon exposure in a spa with radon-containing water. Genetic analysis identified a p.S249C FGFR3 hotspot mutation in 1 lesion, supporting the diagnosis of SLs. It remains elusive whether the occupational exposure to radon-containing water in addition to the recreational UV light exposure caused the unusual distribution of the SLs in this patient.