Rainer Biedermann

Extracorporeal shock waves in the treatment of nonunions.

BACKGROUND Nonunion remains a major complication after skeletal trauma. In the last decade, extracorporeal shock wave therapy has become a common tool for the treatment of nonunions. To date, no prospective, randomized trial has been conducted to show the efficacy of this form of treatment. METHODS This study was performed to determine the value of extracorporeal shock wave therapy for nonunions. Previous published results in the literature and our own clinical results were analyzed and related to the natural history of bony union. RESULTS No study has proven that extracorporeal shock wave therapy improves bone healing. Clinical studies reporting the acceleration of union after application of shock waves instead seem to misinterpret the natural history of bony union. CONCLUSION No evidence supports the treatment of pseudarthroses with extracorporeal shock waves. A randomized, prospective, clinical trial with a control group has to be performed before a final decision can be made regarding this indication for extracorporeal shock wave therapy.

Reproducible assessment of radiolucent lines in total knee arthroplasty.

The Knee Society Total Knee Arthroplasty Radiographic Evaluation and Scoring System was introduced to encourage uniform reporting of radiographic outcome. However, the method for evaluation of radiolucent lines has been shown to be unreliable. Because it has been shown that reducing the complexity of classification systems increases reliability and reproducibility, we questioned whether a simplification of the Radiographic Evaluation and Scoring System would improve reliability and reproducibility. A new system for assessment of radiolucent lines was introduced, and the interobserver reliability and intraobserver reproducibility were studied in 100 patients with 120 total knee replacements. For the new system the mean kappa intraobserver reproducibility coefficient was 0.71 (range, 0.62–0.85) for the femoral component, 0.86 (range, 0.80–0.96) for the tibial component, and 0.58 (range, 0.46–0.75) for the patella prosthesis. The mean interobserver reliability coefficient among three observers was 0.61 (range, 0.45–0.72) for the femoral component, 0.82 (range, 0.73–0.88) for the tibial component, and 0.58 (range, 0.43–0.72) for the patella prosthesis. The new system for assessment of radiolucent lines increased reliability and reproducibility and should supplement the Knee Society’s Radiographic Evaluation and Scoring System. Level of Evidence: Diagnostic study, Level II-1 (development of diagnostic criteria on basis of consecutive patients—with universally applied reference gold standard). See the Guidelines for Authors for a complete description of levels of evidence.

A role of TRAIL in killing osteoblasts by myeloma cells

In multiple myeloma (MM), neoplastic plasma cells accumulate in the bone marrow where their survival, proliferation, and apoptosis are controlled at multiple levels by interaction with the bone marrow microenvironment. Myeloma cells actively control these interactions by activating stromal and endothelial cells for production of survival factors, such as interleukin‐6, and suppressing other cell types such as erythroblasts, normal B cell progenitors, and T‐cells. In the present study, we identified primary osteoblasts as additional potential targets for myeloma cell‐mediated suppression which was partly dependent on the death receptor ligand TRAIL. Besides killing of osteoblasts, myeloma cell lines sensitized osteoblasts to cell death mediated by recombinant TRAIL, whereas primary osteoblasts protected myeloma cells from TRAIL‐mediated apoptosis that was mediated by osteoprotegerin (OPG). Besides increase of osteoclastogenesis and osteoclast activity, suppression of bone‐forming cells by myeloma cells might contribute to bone loss in MM patients. In addition, clinical development of recombinant TRAIL as anti‐myeloma therapy should include evaluation of potential side effects on viability of normal bone cells.

Cost-effectiveness of universal ultrasound screening compared with clinical examination alone in the diagnosis and treatment of neonatal hip dysplasia in Austria

Between 1978 and 1997 all newborns in the Austrian province of Tyrol were reviewed regarding hip dysplasia and related surgery. This involved a mean of 8257 births per year (7766 to 8858). Two observation periods were determined: 1978 to 1982 (clinical examination alone) and 1993 to 1997 (clinical examination and universal ultrasound screening). A retrospective analysis compared the number and cost of interventions due to hip dysplasia in three patient age groups: A, 0 to < 1.5 years; B, ≥ 1.5 to < 15 years; and C, ≥ 15 to < 35 years. In group A, there was a decrease in hip reductions from a mean of 25.2 (SD 2.8) to 7.0 (SD 1.4) cases per year. In group B, operative procedures decreased from a mean of 17.8 (SD 3.5) to 2.6 (SD 1.3) per year. There was a 75.9% decrease in the total number of interventions for groups A and B. An increase of €57,000 in the overall cost per year for the second period (1993 to 1997) was seen, mainly due to the screening programme. However, there was a marked reduction in costs of all surgical and non-surgical treatments for dysplastic hips from €410,000 (1978 to 1982) to €117,000 (1993 to 1997). We believe the small proportional increase in costs of the universal ultrasound screening programme is justifiable as it was associated with a reduction in the number of non-surgical and surgical interventions. We therefore recommend universal hip ultrasound screening for neonates.

Aseptic stem loosening in primary THA: migration analysis of cemented and cementless fixation

Early migration has reportedly been predictive for later implant failure. Using four different migration patterns, this study aimed to analyse migration behaviour of the two types of implant fixation—cemented and cementless—throughout the process of loosening. Migrational behaviour of 69 revised stems (49 cemented, 20 uncemented) was analysed retrospectively with EBRA-FCA (Einzel-Bild-Röntgen-Analyse, Femoral Component Analysis). Uncemented stems failed after early and late onset migration alike, while late migration was the predominant pattern in cemented stems. Mean prosthetic failure after early migration occurred 5.8 (±4.4) years postoperatively due to insufficient primary stability. Initially stable stems with late onset migration were revised after 12.4 (±4.5) years. Measurement of early migration was found to be a valuable tool to screen short-term and mid-term failure. In the long run the method’s sensitivity decreased. Late onset migration, however, preceded long-term failure by a mean of three years.RésuméLe but de cette étude est de rapporter les migrations précoces en rapport avec une prévision d’échec des implants. Pour cela, nous avons utilisé quatre groupes de PTH avec différentes migrations à propos du devenir de deux types de fixation des implants, cimentés ou non cimentés. l’évolution de la migration sur 69 prothèses (pièces fémorales 49 cimentées, 20 non cimentées) ont été analysées de façon rétrospective selon la méthode EBRA-FCA les pièces fémorales non cimentées peuvent présenter des échecs précoces et tardifs, alors que les prothèses cimentées ne présentent que des échecs tardifs. L’échec le plus fréquent est la migration qui se fait en moyenne à 5,8 (±4,4) ans post-opératoire en relation avec une insuffisance de stabilité primaire. Les pièces fémorales stables ont une migration beaucoup plus tardive et ne sont révisées qu’après 12,4 ans (±4,5). la mesure de la migration précoce permet de dépister les échecs à court et moyen terme. La méthode décrite est fiable, les migrations tardives cependant sont précédées d’un échec à long terme et ont évolué pendant au moins trois ans avant la reprise.

T cells in multiple myeloma display features of exhaustion and senescence at the tumor site

BackgroundMultiple myeloma is an incurable plasma cell malignancy that is mostly restricted to the bone marrow. Cancer-induced dysfunction of cytotoxic T cells at the tumor site may be responsible for immune evasion and therapeutical failure of immunotherapies. Therefore, enhanced knowledge about the actual status of T cells in myeloma bone marrow is urgently needed. Here, we assessed the expression of inhibitory molecules PD-1, CTLA-4, 2B4, CD160, senescence marker CD57, and CD28 on T cells of naive and treated myeloma patients in the bone marrow and peripheral blood and collected data on T cell subset distribution in both compartments. In addition, T cell function concerning proliferation and expression of T-bet, IL-2, IFNγ, and CD107a was investigated after in vitro stimulation by CD3/CD28. Finally, data was compared to healthy, age-matched donor T cells from both compartments.MethodsMulticolor flow cytometry was utilized for the analyses of surface molecules, intracellular staining of cytokines was also performed by flow cytometry, and proliferation was assessed by 3H-thymidine incorporation. Statistical analyses were performed utilizing unpaired T test and Mann-Whitney U test.ResultsWe observed enhanced T cell exhaustion and senescence especially at the tumor site. CD8+ T cells expressed several molecules associated with T cell exhaustion (PD-1, CTLA-4, 2B4, CD160) and T cell senescence (CD57, lack of CD28). This phenotype was associated with lower proliferative capacity and impaired function. Despite a high expression of the transcription factor T-bet, CD8+ T cells from the tumor site failed to produce IFNγ after CD3/CD28 in vitro restimulation and displayed a reduced ability to degranulate in response to T cell stimuli. Notably, the percentage of senescent CD57+CD28− CD8+ T cells was significantly lower in treated myeloma patients when compared to untreated patients.ConclusionsT cells from the bone marrow of myeloma patients were more severely impaired than peripheral T cells. While our data suggest that terminally differentiated cells are preferentially deleted by therapy, immune-checkpoint molecules were still present on T cells supporting the potential of checkpoint inhibitors to reactivate T cells in myeloma patients in combination therapies. However, additional avenues to restore anti-myeloma T cell responses are urgently needed.

Are our expectations bigger than the results we achieve? a comparative study analysing potential advantages of ankle arthroplasty over arthrodesis.

PurposePrior studies have reported improved gait performance and kinematics after total ankle arthroplasty (TAR) compared to ankle arthrodesis (AAD). Given these findings, AAD has been primarily considered as a salvage procedure that may lead to adjacent joint degeneration.MethodsA total of 101 TAR and 40 screw arthrodeses were enrolled in a retrospective study with a prospectively designed follow-up examination that included gait analysis and outcome assessment with the AOFAS hindfoot score and FAOS questionnaire.ResultsSignificant asymmetry in gait and reduced range of motion compared to normal remained after both procedures. Subjective outcome improved after both procedures, and pain was significantly better after TAR. Limited functional gains after TAR and joint degeneration to the same degree after both procedures was seen in the mid-term. Hindfoot fusion seemed to have a greater impact on postoperative function than ankle arthrodesis.ConclusionConsidering only minor functional gains of TAR compared to AAD the implantation of current TAR designs in large patient series may be questioned.

Effect of Coronal and Sagittal Alignment on Outcome After Mobile-Bearing Total Ankle Replacement

Background: Comparably high revision rates are reported after total ankle replacement (TAR). Therefore, further critical analysis of the influence of implant position on clinical outcome is necessary. Methods: We analyzed the reliability and predictive value of previously published pre- and postoperative coronal and sagittal parameters in routine ankle radiographs on the clinical outcome of 84 HINTEGRA total ankle replacements (Newdeal, Lyon, France; Integra, Plainsboro, New Jersey). Mean follow-up was 4.0 years, and 15.5% of the TARs had revision surgery. Results: Mean postoperative American Orthopaedic Foot & Ankle Society ankle-hindfoot score was 71.3; mean postoperative verbal rating scale for pain was 3.1; and mean postoperative ankle range of motion was 26.4 degrees. Most tested radiologic parameters showed moderate or high intra- and interobserver reliability. With the numbers available, no significant difference in clinical outcome for all tested radiologic parameters could be detected. Conclusion: Our results indicate that mild malalignment of TAR, as assessed on routine ankle radiographs, did not affect midterm clinical outcome after TAR. Further multicenter studies with longer follow-up are needed to support our findings. Level of Evidence: Level III, comparative series.

Radiographic evaluation of the Duraloc cup after 4 years

We implanted 71 metal-backed, porous-coated, hemispheric, press-fit Duraloc-100 cups in 68 consecutive patients. In 61 patients, the femoral stem was a cementless Spotorno and in ten a cemented Lubinus SP II. A 28-mm Biolox ceramic head was used with both stems. After an average follow-up of 4 (3.7–5.9) years, we examined 67 hips. Radiolucencies were described in three zones according to DeLee and Charnley, and migration was measured on serial radiographs using the computer-assisted EBRA method. Total migration of more than 1 mm within the first 2 years occurred in 22/62 cups. Nine cups showed more than 1.5 mm total migration within the first 2 years and more than 2 mm within the whole period. The presence of post-operative radiolucencies correlated significantly with a total migration value of more than 2 mm within the first 2 years (p=0.02). Post-operative radiolucencies in zone 1 correlated with a total migration value of more than 2 mm within the first 2 years (p=0.027) and more than 2.5 mm within the whole period (p=0.051). These correlation values might reflect the quality of operative technique, particularly reaming, and implant selection.RésuméNous avons implanté 71 cupules métal-back hémisphérique press-fit, revêtement poreux, Duraloc-100 chez 68 malades consécutifs. Pour 61 malades la tige fémorale était une Spotorno sans ciment et,pour dix, un tige cimenté Lubinus SP II. Un tête céramique Biolox 28 mm a été utilisée avec les deux tiges. Après une moyenne de suivi de 4 ans (3.7–5.9) nous avons examiné 67 hanches. Les liserés radiologiques ont été décrits dans les trois zones de DeLee et Charnley, et la migration a été mesurée sur des radiographies sérielles en utilisant la méthode EBRA assistée par ordinateur. Une migration totale de plus de 1 mm dans les deux premières années s’est produites dans 22/62 cupules. Neuf cupules avaient une migration totale de plus de 1.5 mm dans les deux premières années et de plus de 2 mm dans la période entière. La présence de liserés radiologiques postopératoires était corrélé avec une migration de plus de 2 mm dans les deux premières années (p=0.02). Les liserés radiologiques postopératoires en zone 1 correspondaient avec une valeur de migration de plus de 2 mm dans les deux premières années (p=0.027) et de plus de 2,5 mm dans la période entière (p=0.051). Ces valeurs peuvent refléter la qualité de la technique opératoire, en particulier le fraisage, et la sélection de l’implant.

Effect of Knee Brace Type on Braking Response Time During Automobile Driving

PURPOSE To assess driving ability (brake response time [BRT]) with commonly used knee braces. METHODS Sixty-four healthy participants (32 women and 32 men) participated in our study. BRT was assessed using a custom-made driving simulator. We assessed BRT for 5 different commonly used knee braces (right leg) used in 9 different settings: without a knee brace (control group); with a typical postoperative knee brace with adjustable range of motion (ROM) and the settings of 0° to 30°, 0° to 60°, 0° to 90°, and 20° to 90° (extension and flexion); and with an unloading knee brace for moderate to severe unicompartmental osteoarthritis, an orthosis for ligament instabilities, a knee brace for patellofemoral disorders, and an elastic knee bandage. RESULTS The 64 participants (mean age, 33.5 years) showed significantly impaired BRT with the typical postoperative brace set at an ROM of 0° to 30° (673 milliseconds, P < .001), ROM of 0° to 60° (629 milliseconds, P < .001), ROM of 0° to 90° (607 milliseconds, P = .001), and ROM of 20° to 90° (602 milliseconds, P = .005) compared with the control group. However, no such impaired BRT was found for any other investigated knee brace. CONCLUSIONS Right-sided ROM-restricting knee braces involve significant impairment of BRT in healthy participants. No such prolonged BRT was found for a patellofemoral realignment brace, a ligament brace, a valgus/osteoarthritis brace, or an elastic knee bandage. However, our findings should be viewed in light of the limitations of the study, which are (1) the lack of a defined decrease in BRT that could lead to an accident and (2) uncertainty of whether the statistical differences are also clinically important. LEVEL OF EVIDENCE Level II, lesser-quality randomized controlled trial.