Bernd Rolauffs

Changes in the treatment of acetabular fractures over 15 years: Analysis of 1266 cases treated by the German Pelvic Multicentre Study Group (DAO/DGU)

Epidemiological, clinical and radiological data of 1266 patients with a unilateral acetabular fracture of up to 29 hospitals was reviewed. Three time periods, 1991-1993 (Registry I; n=359), 1998-2000 (Registry II; n=503), and 2005-2006 (Registry III; n=404) were compared with regard to injury pattern and severity, fracture type, and chosen nonoperative vs. operative treatment to elucidate changes over time in the treatment of acetabular fractures. In the operatively treated group, time to operation, surgical approach, fracture fixation implants and fracture reduction quality were examined. 641 (50.6%) patients with isolated acetabular fractures, 410 (32.4%) multiple injured and 215 (17.0%) polytrauma patients with 642 (50.7%) simple and 624 (49.3%) associated acetabular fractures were evaluated. In the time period from 1991 to 2006, the rate of operative treatments increased nationwide to 77% (rho<0.001). The distribution of fracture types involving the anterior and posterior wall changed with age (rho<0.001). Across all registries, 583 (68.0%) operations were performed within 7 days, 212 (24.7%) operations between 7 and 14 days and 54 (6.3%) operations were performed later than 14 days after injury. An anatomical reduction (0-1mm displacement) was achieved in 551 (64%) acetabular fractures. The obtained reduction quality did not correlate with time to operation, was lower in associated than in simple fracture types, and also lower in patients with isolated acetabular fractures than in polytrauma patients. Most importantly, the fracture reduction quality did not improve over time despite a higher frequency of surgical interventions. The Kocher-Langenbeck approach was preferred in the nineties in nearly three quarters of all operative procedures. Currently, the Kocher-Langenbeck and the ilioinguinal approaches are used equally often. The fracture fixation did not change over time and is achieved in 51% with plates in combination with single screws. This multisurgeon series illustrates a nationwide performance in acetabular fracture management. Despite changes in the chosen approaches and an increased surgical frequency, the operative treatment of acetabular fractures of the last 15 years did not lead to an increased reduction quality. Therefore, the rarity and complexity of acetabular fractures demands further specific teaching by experienced acetabular surgeons, scientific research and clinical outcome evaluation.

Arthroscopic Treatment of Osteochondral Lesions of the Ankle With Matrix-Associated Chondrocyte Implantation: Early Clinical and Magnetic Resonance Imaging Results

Background: Conventional autologous chondrocyte transplantation in the ankle often requires tibial or fibular osteotomies with potential morbidity for the patient. Advances in biotechnology and surgical techniques have resulted in the development of matrix-associated chondrocyte implantation (MACI). As the chondrocyte-loaded scaffold can be applied arthroscopically, this procedure is especially useful for the treatment of osteochondral defects in the ankle. Hypothesis: Arthroscopic MACI is a safe procedure in the ankle with good clinical and magnetic resonance imaging results. Study Design: Case series; Level of evidence, 4. Methods: The authors reviewed all patients (n = 18) who had arthroscopic MACI for osteochondral lesions of the ankle (n = 19) between February 2006 and May 2008 clinically and with magnetic resonance imaging. The pain and disability module of the Foot Function Index (FFI), the American Orthopaedic Foot & Ankle Society (AOFAS) clinical rating system, the Core Scale of the Foot and Ankle Module of the American Academy of Orthopaedic Surgeons (AAOS) Lower Limb Outcomes Assessment Instruments, and the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score were used. The clinical results up to 3 years after MACI (mean follow-up, 24.5 months) were compared with preoperative data for 14 cases and the magnetic resonance imaging data for all 19. Results: A significant improvement (50.3% ± 13.2%) in all clinical scores was noted (FFI pain before MACI: 5.5 ± 2.0, after MACI: 2.8 ± 2.2; FFI disability before MACI: 5.0 ± 2.3, after MACI: 2.6 ± 2.2; AOFAS before MACI: 58.6 ± 16.1, after MACI: 80.4 ± 14.1; AAOS standardized mean before MACI: 59.9 ± 16.0, after MACI: 83.5 ± 13.2; AAOS normative score before MACI: 23.0 ± 13.0, after MACI: 42.2 ± 10.7). According to the AOFAS Hindfoot score, 64% were rated as excellent and good, whereas 36% were rated fair and poor. The results correlated with the age of the patient and the duration of symptoms, but not with the size of the lesion. Sixteen patients (89%) reported regular sports activities before the onset of symptoms; 13 of them (81%) returned to sports after the MACI, 56% (n = 9) to the same level. The mean MOCART score was 62.4 ± 15.8 points. In general, there was no relation between MOCART score and clinical outcome, although the filling of the defect showed some correlation with the AAOS score. Conclusion: Arthroscopic MACI is a safe procedure for the treatment of osteochondral lesions in the ankle with overall good clinical and magnetic resonance imaging results.

Human term placenta-derived mesenchymal stromal cells are less prone to osteogenic differentiation than bone marrow-derived mesenchymal stromal cells.

Mesenchymal stromal cells (MSC) can be isolated from different tissues. They are capable of differentiating in vitro, for example, to osteoblasts, chondrocytes, or adipocytes. In contrast to CD34 for hematopoietic stem cells, a distinct MSC-defining antibody is not available. Further, for hematopoietic cells lineage-defining antigens such as CD3 or CD20 are known. In contrast, for MSC-derived cells lineage-associated cell surface markers are far from being established. We therefore investigated expression of cell surface antigens on human term placenta-derived MSC (pMSC) in more detail and correlated expression pattern to the osteogenic differentiation capacity of the MSC. We report that pMSC expressed the typical cell surface antigens at levels comparable to bone marrow-derived MSC (bmMSC), including CD73, CD90, and CD105, but did not express CD11b, CD34, and CD45. Further, CD164, TNAP, and the W5C5 antigens were detected on pMSC, whereas CD349 was not observed. Some pMSC expressed CD146 at low or moderate levels, and their osteogenic differentiation potential was weak. In contrast, bmMSC expressed CD146 at high levels, expression of alkaline phosphatase was significantly higher, and they presented a pronounced osteogenic differentiation potential. We conclude that MSC from different sources differ in their expression of distinct markers, and that this may correlate in part with their lineage determination. Thus, a higher percentage of bmMSC expressed CD146 at prominent levels and such cells may be better suited for bone repair. In contrast, many pMSC expressed CD146 at low or moderate levels. They, therefore, may be suitable for applications in which osteogenic differentiation is undesirable.

Remodeling of Articular Cartilage and Subchondral Bone After Bone Grafting and Matrix-Associated Autologous Chondrocyte Implantation for Osteochondritis Dissecans of the Knee

Background: Osteochondritis dissecans (OCD) of the knee is a challenging problem. Previously, the authors implemented a novel 1-step surgical procedure for OCD treatment consisting of matrix-associated autologous chondrocyte implantation (ACI) and simultaneous bone reconstruction including the subchondral lamina. Purpose: This study presents the 2-to 5-year results after this technique, assessing correlations of clinical function and cartilage and bone remodeling processes. Study Design: Case series; Level of evidence, 4. Methods: Twenty-six patients with symptomatic condylar knee OCD (International Cartilage Repair Society OCD III/IV) were treated with matrix-associated ACI and monocortical cancellous cylinders for defect filling and subchondral bone plate reconstruction using cortical graft layers as novel subchondral lamina. Evaluations were performed with clinical rating scales and 1.5-T magnetic resonance imaging using the magnetic resonance observation of cartilage repair tissue (MOCART) score and a newly implemented subchondral lamina remodeling grade. Results: The defect size was 5.3 ± 2.3 cm2. The defect depth was 8.7 ± 2.4 mm. After a follow-up of 39.8 ± 12.0 months, all scores improved significantly. Nineteen patients (73%) reached good/excellent results in the Lysholm-Gillquist score (preoperatively: 53.2 ± 18.0 points; latest follow-up: 88.5 ± 9.5 points) and the Cincinnati knee rating score (preoperatively: 51.7 ± 13.0 points; latest follow-up: 84.6 ± 11.7 points) and significant improvements in the subjective International Knee Documentation Committee (IKDC) score by 27.9% (preoperatively: 50.5% ± 16.1%; latest follow-up: 78.4% ± 13.4%). The MOCART score reached 62.4 ± 18.9 points. The clinical improvement and tissue remodeling occurred simultaneously and timed; thus, the cartilage defect filling and the lamina remodeling grades correlated significantly with each other, the follow-up time, and almost all clinical scores. Conclusion: The simultaneous reconstruction of deep osteochondral defects of the knee OCD with monocortical cancellous cylinders and matrix-associated ACI is a biological, 1-step alternative to osteochondral cylinder transfer or conventional ACI that leads to good clinical and magnetic resonance imaging results after an intermediate follow-up period. The present study demonstrated simultaneous remodeling processes of articular cartilage repair tissue and subchondral lamina; this synchronization is not yet understood and deserves further investigation.

Computer-assisted periacetabular screw placement: Comparison of different fluoroscopy-based navigation procedures with conventional technique

The current gold standard for operatively treated acetabular fractures is open reduction and internal fixation. Fractures with minimal displacement may be stabilised by minimally invasive methods such as percutaneous periacetabular screws. However, their placement is a demanding procedure due to the complex pelvic anatomy. The aim of this study was to evaluate the accuracy of periacetabular screw placement assessing pre-defined placement corridors and comparing different fluoroscopy-based navigation procedures and the conventional technique. For each screw an individual periacetabular placement corridor was preoperatively planned using the planning software iPlan CMF(©) 3.0 (BrainLAB). 210 screws (retrograde anterior column screws, retrograde posterior column screws, supraacetabular ilium screws) were placed in an artificial Synbone pelvis model (30 hemipelves) and in human cadaver specimen (30 hemipelves). 2D- and 3D-fluoroscopy-based navigation procedures were compared to the conventional technique. Insertion time and radiation exposure to specimen were also recorded. The achieved screw position was postoperatively assessed by an Iso-C(3D) scan. Perforations of bony cortices or articular surfaces were analysed and the screw deviation severity (difference of the operatively achieved screw position and the preoperatively planned screw position in reference to the pre-defined corridors) was determined using image fusion. Using 3D-fluoroscopy-based navigation, the screw perforation rate (7%) was significantly lower compared to 2D-fluoroscopy-based navigation (20%). For all screws, the deviation severity was significantly lower using a 3D- compared to a 2D-fluoroscopy-based navigation and the conventional technique. Analysing the posterior column screws, the screw deviation severity was significantly lower using 3D- compared to 2D-fluoroscopy-based navigation. However, for the anterior column screw, the screw deviation severity was similar regardless of the imaging method. Despite the advantages of the 3D-fluoroscopy-based navigation, this method led to significantly longer total procedure and fluoroscopic times, and the applied radiation dose was significantly higher. Percutaneous periacetabular screw placement is demanding. Especially for posterior column screws, due to a lower perforation rate and a higher accuracy in periacetabular screw placement, 3D-fluoroscopy-based navigation procedure appears to be the method of choice for image guidance in acetabular surgery.

Regeneration of cartilage and bone by defined subsets of mesenchymal stromal cells—Potential and pitfalls☆

Mesenchymal stromal cells, also referred to as mesenchymal stem cells, can be obtained from various tissues. Today the main source for isolation of mesenchymal stromal cells in mammals is the bone marrow. Mesenchymal stromal cells play an important role in tissue formation and organogenesis during embryonic development. Moreover, they provide the cellular and humoral basis for many processes of tissue regeneration and wound healing in infancy, adolescence and adulthood as well. There is increasing evidence that mesenchymal stromal cells from bone marrow and other sources including term placenta or adipose tissue are not a homogenous cell population. Only a restricted number of appropriate stem cells markers have been explored so far. But routine preparations of mesenchymal stromal cells contain phenotypically and functionally distinct subsets of stromal cells. Knowledge on the phenotypical characteristics and the functional consequences of such subsets will not only extend our understanding of stem cell biology, but might allow to develop improved regimen for regenerative medicine and wound healing and novel protocols for tissue engineering as well. In this review we will discuss novel strategies for regenerative medicine by specific selection or separation of subsets of mesenchymal stromal cells in the context of osteogenesis and bone regeneration. Mesenchymal stromal cells, which express the specific cell adhesion molecule CD146, also known as MCAM or MUC18, are prone for bone repair. Other cell surface proteins may allow the selection of chondrogenic, myogenic, adipogenic or other pre-determined subsets of mesenchymal stromal cells for improved regenerative applications as well.

Low Osteogenic Differentiation Potential of Placenta-Derived Mesenchymal Stromal Cells Correlates with Low Expression of the Transcription Factors Runx2 and Twist2

Recent studies indicated that mesenchymal stromal cells from bone marrow (bmMSC) differ in their osteogenic differentiation capacity compared to MSC from term placenta (pMSC). We extended these studies and investigated the expression of factors involved in regulation of bone metabolism in both cell types. To this end, MSC were expanded in vitro and characterized. The total transcriptome was investigated by microarrays, and for selected genes, the differences in gene expression were explored by quantitative reverse transcriptase-polymerase chain reaction, immunocytochemistry, and flow cytometry. We report that bmMSC and pMSC share expression of typical lineage surface markers, including CD73, CD90, CD105, and lack of CD14, CD34, and CD45. However, according to transcriptome analyses, they differ significantly in their expression of more than 590 genes. Factors involved in bone metabolism, including alkaline phosphatase (P<0.05), osteoglycin (P<0.05), osteomodulin (P<0.05), runt-related transcription factor 2 (Runx2) (P<0.04), and WISP2 (P<0.05), were expressed at significantly lower levels in pMSC, but twist-related protein 2 (Twist2) (P<0.0002) was expressed at significantly higher levels. The osteogenic differentiation capacity of pMSC was very low. The adipogenic differentiation was somewhat more prominent in bmMSC, while the chondrogenic differentiation seemed not to differ between bmMSC and pMSC, as determined by histochemical staining. However, expression and induction of peroxisome proliferator-activated receptor gamma-2 (PPARγ2) and Sox9, factors involved in early adipogenesis and chondrogenesis, respectively, were higher in bmMSC. We conclude that despite many similarities between bmMSC and pMSC, when expanded under identical conditions, they vary considerably with respect to their in vitro differentiation potential. For regenerative purposes, the choice of MSC may therefore influence the outcome of a treatment considerably.

Proximal humeral fractures in children and adolescents.

Background: The purpose of the study was to investigate possible reasons for the failure of closed reduction of proximal humerus fractures in children and adolescents. We assessed the rate of soft tissue entrapment, and we also investigated the long-term clinical and radiological results after an age- and deformity-focused treatment regimen according to national guidelines. Methods: Forty-three patients were included in the study. Ten (mean age, 12.4 years; range, 6-16 years) of the patients were treated conservatively. The remaining 33 patients (mean age, 14 years; range, 6-18 years) were treated surgically (n = 2 Neer grade 2, n = 16 Neer grade 3, and n = 15 Neer grade 4) with either closed (n = 16) or open reduction with internal fixation. In 17 fractures, closed anatomical reduction of the fracture under general anesthesia was not possible. Subsequent open reduction and Kirschner wire or screw fixation (n = 12) or plate fixation (n = 5) was necessary. In 9 of these 17 fractures (5 fractures were totally displaced fractures), closed reduction was impossible because of the entrapment of periost (n = 2) or the biceps tendon with parts of the periost (n = 7). At follow-up, the clinical assessment included a structured interview, a detailed physical examination, and the assessment of overall shoulder function with the Constant score. Results: Operative and postoperative complications did not occur. All surgically treated fractures anatomically reduced and healed without loss of reduction. At a mean follow-up of 39 months (range, 12-118 months), all patients who were evaluated had excellent results according to the Constant score and had a normal range of motion and excellent strength of the shoulder joint. Conclusions: A failed closed reduction should be interpreted as a possible soft tissue entrapment most likely because of the long biceps tendon. Those cases should be addressed with open reduction and removal of the entrapped structures. If anatomical reduction is achieved and maintained until fracture healing, excellent functional and radiological results can be expected from an age- and deformity-focused treatment regimen for children and adolescents with proximal humeral fractures. Level of Evidence: Level 4 (Therapeutic study).

Effect of Proximal Humeral Fractures on the Age-Specific Prevalence of Rotator Cuff Tears

BACKGROUND This study examined the effect of proximal humeral fractures on the age- and shoulder-specific prevalence of rotator cuff tears (RCTs) as well as the association with fracture severity, patient age, and clinical outcome. METHODS Sixty-three fractures were treated conservatively; in 114 cases, minimally invasive osteosynthesis, and in 125 cases, open reduction and plate fixation were performed without rotator cuff reconstruction. After 4.4 years, all 302 patients were clinically and sonographically examined. RESULTS We examined 139 two-part, 95 three-part, and 68 four-part fractures according to Neer and 134 A, 86 B, and 82 C fractures according to the AO classification. There were 52 patients (17%) with a complete rotator tear (RCT) only at the injured shoulder and 11 patients (4%) with a complete RCT only at the contralateral shoulder (p < 0.0001). Independent of the patients age at follow-up, the prevalence of an RCT in the fractured shoulder was 13% higher than the prevalence in the opposite shoulder. Four-part fractures showed a significant association with a complete RCT (p = 0.047).Of 74 patients with a satisfactory or poor Constant Score, 33 (44.6%) had RCTs. In the remaining 228 patients with a good to excellent result, only 26 (11.4%) had RCTs. We showed that 66% of the RCTs observed at the fractured shoulder were caused by trauma. There was no association between treatment modality and a complete RCT. CONCLUSION RCTs may need special attention in initial diagnostics, management, and follow-up especially in severe proximal humeral fractures.

Proliferative re-modeling of the spatial organization of human superficial chondrocytes distant to focal early osteoarthritis (OA)

OBJECTIVE Human superficial chondrocytes show distinct spatial organizations, and they commonly aggregate near osteoarthritic (OA) fissures. The aim of this study was to determine whether remodeling or destruction of the spatial chondrocyte organization might occur at a distance from focal (early) lesions in patients with OA. METHODS Samples of intact cartilage (condyles, patellofemoral groove, and proximal tibia) lying distant from focal lesions of OA in grade 2 joints were compared with location-matched nondegenerative (grade 0-1) cartilage samples. Chondrocyte nuclei were stained with propidium iodide, examined by fluorescence microscopy, and the findings were recorded in a top-down view. Chondrocyte arrangements were tested for randomness or significant grouping via point pattern analyses (Clark and Evans Aggregation Index) and were correlated with the OA grade and the surface cell densities. RESULTS In grade 2 cartilage samples, superficial chondrocytes were situated in horizontal patterns, such as strings, clusters, pairs, and singles, comparable to the patterns in nondegenerative cartilage. In intact cartilage samples from grade 2 joints, the spatial organization included a novel pattern, consisting of chondrocytes that were aligned in 2 parallel lines, building double strings. These double strings correlated significantly with an increased number of chondrocytes per group and an increased corresponding superficial zone cell density. They were observed in all grade 2 condyles and some grade 2 tibiae, but never in grade 0-1 cartilage. CONCLUSION This study is the first to identify a distinct spatial reorganization of human superficial chondrocytes in response to distant early OA lesions, suggesting that proliferation had occurred distant from focal early OA lesions. This spatial reorganization may serve to recruit metabolically active units as an attempt to repair focal damage.