Proof-of-concept for the detection of early osteoarthritis pathology by clinically applicable endomicroscopy and quantitative AI-supported optical biopsy.

OBJECTIVE: Clinical trials for osteoarthritis (OA), the leading cause of global disability, are unable to pinpoint the early, potentially reversible disease with clinical technology. Hence, disease-modifying drug candidates cannot be tested early in the disease. To overcome this obstacle, we asked whether early OA-pathology detection is possible with current clinical technology. METHODS: We determined the relationship between two sensitive early OA markers, atomic force microscopy (AFM)-measured human articular cartilage (AC) surface stiffness, and location-matched superficial zone chondrocyte spatial organizations (SCSOs), asking whether a significant loss of surface stiffness can be detected in early OA SCSO stages. We then tested whether current clinical technology can visualize and accurately diagnose the SCSOs using an approved probe-based confocal laser-endomicroscope and a random forest (RF) model. RESULTS: We demonstrated a correlation between AC surface stiffness and the SCSO (rrm = -0.91; 95%CI: -0.97, -0.73), and an extensive loss of surface stiffness specifically in those ACs with early OA-typical SCSO (95%CIs: string SCSO: 269-173 kPa, double string SCSO: 77-46 kPa). This established the SCSO as a visualizable, functionally relevant surrogate marker of early OA AC surface pathology. Moreover, SCSO-based stiffness discrimination worked well in each patient's AC. We then demonstrated feasibility of visualizing the SCSO by clinical laser-endomicroscopy and, importantly, accurate SCSO diagnosis using RF. CONCLUSION: We present the proof-of-concept of early OA-pathology detection with available clinical technology, introducing a future-oriented, AI-supported, non-destructive quantitative optical biopsy for early disease detection. Operationalizing SCSO recognition, this approach allows testing for correlations between local tissue architectures with other experimental and clinical read-outs, but needs clinical validation and a larger sample size for defining diagnostic thresholds.

Chondrogenic potential of IL-10 in mechanically injured cartilage and cellularized collagen ACI grafts.

OBJECTIVE: The application of adjunctive mediators in Autologous chondrocyte implantation (ACI) techniques might be useful for improving the dedifferentiated chondrocyte phenotype, to support neocartilage formation and inhibit post-traumatic cartilage destruction. In this study we examined if (a) interleukin 10 treatment can cause chondrogenic phenotype stabilization and matrix preservation in mechanically injured cartilage and if (b) IL-10 can promote chondrogenesis in a clinically applied collagen scaffold for ACI treatment. MATERIALS AND METHODS: For (a) bovine articular cartilage was harvested, subjected to an axial unconfined injury and treated with bovine IL-10 (1-10,000 pg/ng/ml). For (b) a post-operatively remaining ACI graft was treated with human IL-10. Expression levels of type I/II/X collagen, SOX9 and aggrecan were measured by qPCR (a,b). After 3 weeks cell death was analyzed (nuclear blebbing and TUNEL assay) and matrix composition was determined by GAG measurements and immunohistochemistry (aggrecan, type I/II collagen, hyaluronic acid). STATISTICS: One way ANOVA analysis with Bonferroni's correction. RESULTS: (a) IL-10 stabilized the chondrogenic phenotype after injurious compression and preserved matrix integrity. This was indicated by elevated expression of chondrogenic markers COL2A1, ACAN, SOX9, while COL1A1 and COL10A1 were reduced. An increased GAG content paralleled this and histological staining of type 2 collagen, aggrecan and toluidine blue were enhanced after 3 weeks. (b) IL-10 [100 pg/ml] improved the chondrogenic differentiation of human chondrocytes, which was accompanied by cartilaginous matrix formation after 3 weeks of incubation. CONCLUSION: Interleukin-10 is a versatile adjuvant candidate to control the post-injurious environment in cartilage defects and promote chondrogenesis in ACI grafts.

IL-10 reduces apoptosis and extracellular matrix degradation after injurious compression of mature articular cartilage.

OBJECTIVE: The aim of this study was to examine whether anti-inflammatory interleukin-10 (IL-10) exerts chondroprotective effects in an in vitro model of a single mechanical injury of mature articular cartilage. METHOD: Articular cartilage was harvested from the femoro-patellar groove of adult cows (Bos taurus) and cultured w/o bovine IL-10. After 24 h of equilibration explants were subjected to an axial unconfined compression (50% strain, velocity 2 mm/s, held for 10 s). After 96 h cell death was measured histomorphometrically (nuclear blebbing, NB) and the release of glycosaminoglycans (GAG, DMMB assay) and nitric oxide (NO, Griess-reagent) were analyzed. mRNA levels of matrix degrading enzymes and nitric oxide synthetase were measured by quantitative real time PCR. Differences between groups were calculated using a one-way ANOVA with a Bonferroni post hoc test. RESULTS: Injurious compression significantly increased the number of cells with NB, release of GAG and nitric oxide and expression of MMP-3, -13, ADAMTS-4 and NOS2. Administration of IL-10 significantly reduced the injury related cell death and release of GAG and NO, respectively. Expression of MMP-3, -13, ADAMTS-4 and NOS2 were significantly reduced. CONCLUSION: Joint injury is a complex process involving specific mechanical effects on cartilage as well as induction of an inflammatory environment. IL-10 prevented crucial mechanisms of chondrodegeneration induced by an injurious single compression. IL-10 might be a multipurpose drug candidate for the treatment of cartilage-related sports injuries or osteoarthritis (OA).

Autologous chondrocyte implantation (ACI) for cartilage defects of the knee: A guideline by the working group "Clinical Tissue Regeneration" of the German Society of Orthopaedics and Trauma (DGOU).

BACKGROUND: Autologous chondrocyte implantation (ACI) is an established and well-accepted procedure for the treatment of localised full-thickness cartilage defects of the knee. METHODS: The present review of the working group "Clinical Tissue Regeneration" of the German Society of Orthopaedics and Trauma (DGOU) describes the biology and function of healthy articular cartilage, the present state of knowledge concerning therapeutic consequences of primary cartilage lesions and the suitable indication for ACI. RESULTS: Based on best available scientific evidence, an indication for ACI is given for symptomatic cartilage defects starting from defect sizes of more than three to four square centimetres; in the case of young and active sports patients at 2.5cm(2), while advanced degenerative joint disease needs to be considered as the most important contraindication. CONCLUSION: The present review gives a concise overview on important scientific background and the results of clinical studies and discusses the advantages and disadvantages of ACI. LEVEL OF EVIDENCE: Non-systematic Review.

[Early Diagnosis of Osteoarthritis: Clinical Reality and Promising Experimental Techniques]. / Frühdiagnose der Arthrose: klinische Realität und experimentelle Pipeline.

It is considered that the structural damage in early osteoarthritis (OA) is potentially reversible. It is therefore particularly important for orthopaedic and trauma surgery to develop strategies and technologies for diagnosing early OA processes. This review presents 3 case reports to illustrate the current clinical diagnostic procedure for OA. Experimental techniques with translational character are discussed in the context of the detection of early degenerative processes relevant to OA. Non-invasive imaging methods such as quantitative MRI, ultrasound, optical coherence tomography (OCT), scintigraphy and diffraction-enhanced synchrotron imaging (DEI), as well as biochemical methods and proteomics, are considered. Early detection of OA is reviewed with minimally invasive techniques, such as arthroscopy, as well as the combination of arthroscopic techniques with indentation, spectrometry, and multiphoton microscopy. In addition, a brief summary of macroscopic and histologic scores is presented. Finally, the spatial organisation of joint surface chondrocytes as an image-based biomarker is used to illustrate an early OA detection strategy that focusses on early changes in tissue architecture potentially prior to damage. In summary, multiple translational techniques are able to detect early OA processes but we do not know whether they truly represent the initial events. Moreover, at this point it is difficult to judge the future clinical relevance of these procedures and to compare their efficacy, as there have been comparative studies. However, the expected gain in knowledge will hopefully help us top attain a more comprehensive understanding of early OA and to develop novel methods for its early diagnosis, therapy, and prevention. Overall, the clinical diagnosis of early OA remains one of the greatest challenges of our field. We still face uncharted territory.

Loss of spatial organization and destruction of the pericellular matrix in early osteoarthritis in vivo and in a novel in vitro methodology.

OBJECTIVES: Current repair procedures for articular cartilage (AC) cannot restore the tissue's original form and function because neither changes in its architectural blueprint throughout life nor the respective biological understanding is fully available. We asked whether two unique elements of human cartilage architecture, the chondrocyte-surrounding pericellular matrix (PCM) and the superficial chondrocyte spatial organization (SCSO) beneath the articular surface (AS) are congenital, stable or dynamic throughout life. We hypothesized that inducing chondrocyte proliferation in vitro impairs organization and PCM and induces an advanced osteoarthritis (OA)-like structural phenotype of human cartilage. METHODS: We recorded propidium-iodine-stained fetal and adult cartilage explants, arranged stages of organization into a sequence, and created a lifetime-summarizing SCSO model. To replicate the OA-associated dynamics revealed by our model, and to test our hypothesis, we transduced specifically early OA-explants with hFGF-2 for inducing proliferation. The PCM was examined using immuno- and auto-fluorescence, multiphoton second-harmonic-generation (SHG), and scanning electron microscopy (SEM). RESULTS: Spatial organization evolved from fetal homogeneity, peaked with adult string-like arrangements, but was completely lost in OA. Loss of organization included PCM perforation (local micro-fibrillar collagen intensity decrease) and destruction [regional collagen type VI (CollVI) signal weakness or absence]. Importantly, both loss of organization and PCM destruction were successfully recapitulated in FGF-2-transduced explants. CONCLUSION: Induced proliferation of spatially characterized early OA-chondrocytes within standardized explants recapitulated the full range of loss of SCSO and PCM destruction, introducing a novel in vitro methodology. This methodology induces a structural phenotype of human cartilage that is similar to advanced OA and potentially of significance and utility.

[Treatment of proximal humeral fractures in Germany: Influence of the level of hospital care and the frequency of treatment]. / Behandlung proximaler Humerusfrakturen in Deutschland: Einfluss von Krankenhausversorgungsstufe und Behandlungsfrequenz.

BACKGROUND: Various treatment options exist for displaced proximal humeral fractures. The impact of the level of hospital care and frequency of treatment on current treatment regimens in Germany was analyzed. MATERIAL AND METHODS: A total of 576 hospitals were included. The survey covered questions on frequency, diagnostics, classification, therapy, complications, and clinical scenarios. RESULTS: In all, 48% of the hospitals returned the questionnaire: 73% treat more than 60% of the fractures surgically, mainly with angle-stable implants. The angle-stable plate is the treatment of choice for young patients, but older patients are treated using other treatment options. Problems and complications included malreduction, secondary displacement, screw perforation, avascular necrosis, and impingement. According to treatment indication, implant choice, and common complications, no significant differences between the level of hospital care and frequency of treatment were observed. CONCLUSION: Independent of the level of hospital care and frequency of treatment, there is a trend for head-preserving angular-stable surgery with a homogenous level of treatment in Germany.

Estrogen reduces mechanical injury-related cell death and proteoglycan degradation in mature articular cartilage independent of the presence of the superficial zone tissue.

OBJECTIVE: To study the effect of 17ß-estradiol (E2) and the superficial zone (SFZ) on cell death and proteoglycan degradation in articular cartilage after a single injurious compression in vitro. METHOD: Cartilage explants from the femoropatellar groove of 2 year old cows with or without the SFZ were cultured serum-free with physiological concentrations of E2 and injured by an unconfined single load compression (strain 50%, velocity 2 mm/s). After 96 h cell death was measured histomorphometrically (nuclear blebbing (NB) and TUNEL staining) and release of glycosaminoglycans (GAG) by DMMB assay. RESULTS: Injurious compression increased significantly the number of cells with NB and TUNEL staining and release of GAG. Physiological concentrations of E2 prevented the injury-related cell death and reduced the GAG release significantly in a receptor-mediated manner (shown by co-stimulation with the antiestrogen fulvestrant/faslodex/ICI-182,780). The presence of the SFZ did not alter the NB response to either the mechanical injury or E2, but reduced the overall release of GAG significantly. CONCLUSION: E2 prevents injury-related cell death and GAG release, and might be useful for the development of treatment options for either cartilage-related sports injuries or osteoarthritis (OA). The SFZ does not seem to play an important role in (1) the E2-related tissue response and (2) the mechanically-induced cell death in deeper regions of the explants and GAG release. The latter might be related to the unconfined nature of the injury model.

[Autologous chondrocyte implantation (ACI) for cartilage defects of the knee: a guideline by the working group "Tissue Regeneration" of the German Society of Orthopaedic Surgery and Traumatology (DGOU)]. / Stellenwert der autologen Chondrozytentransplantation (ACT) in der Behandlung von Knorpelschäden des Kniegelenks - Empfehlungen der AG Klinische Geweberegeneration der DGOU.

Autologous chondrocyte transplantation/implantation (ACT/ACI) is an established and recognised procedure for the treatment of localised full-thickness cartilage defects of the knee. The present review of the working group "Clinical Tissue Regeneration" of the German Society of Orthopaedics and Traumatology (DGOU) describes the biology and function of healthy articular cartilage, the present state of knowledge concerning potential consequences of primary cartilage lesions and the suitable indication for ACI. Based on current evidence, an indication for ACI is given for symptomatic cartilage defects starting from defect sizes of more than 3-4 cm2; in the case of young and active sports patients at 2.5 cm2. Advanced degenerative joint disease is the single most important contraindication. The review gives a concise overview on important scientific background, the results of clinical studies and discusses advantages and disadvantages of ACI.

In vitro phenotypic modulation of chondrocytes from knees of patients with osteochondritis dissecans: implications for chondrocyte implantation procedures.

We attempted to characterise the biological quality and regenerative potential of chondrocytes in osteochondritis dissecans (OCD). Dissected fragments from ten patients with OCD of the knee (mean age 27.8 years (16 to 49)) were harvested at arthroscopy. A sample of cartilage from the intercondylar notch was taken from the same joint and from the notch of ten patients with a traumatic cartilage defect (mean age 31.6 years (19 to 52)). Chondrocytes were extracted and subsequently cultured. Collagen types 1, 2, and 10 mRNA were quantified by polymerase chain reaction. Compared with the notch chondrocytes, cells from the dissecate expressed similar levels of collagen types 1 and 2 mRNA. The level of collagen type 10 message was 50 times lower after cell culture, indicating a loss of hypertrophic cells or genes. The high viability, retained capacity to differentiate and metabolic activity of the extracted cells suggests preservation of the intrinsic repair capability of these dissecates. Molecular analysis indicated a phenotypic modulation of the expanded dissecate chondrocytes towards a normal phenotype. Our findings suggest that cartilage taken from the dissecate can be reasonably used as a cell source for chondrocyte implantation procedures.

[No influence of physiotherapy on outcome after open repair of achilles tendon ruptures?]. / Kein Einfluss der Physiotherapie auf das klinische Ergebnis nach operativ behandelter Achillessehnenruptur?

AIM: Many studies have been performed to analyse the influence of surgical techniques and the postoperative aftercare after Achilles tendon ruptures on the outcome. However, there is no study investigating the influence of physiotherapy on outcome after surgical repair and standardised early functional rehabilitation of Achilles tendon rupture, so that this was the objective of the present study. PATIENTS AND METHODS: In this retrospective study, 104 patients with Achilles tendon ruptures, all treated by open repair followed by a standardised early rehabilitation, were evaluated by the Thermann score. The average age was 42 years. We could identify 3 patient groups. Group I (n=23) did not receive any physiotherapy. Group II (n=41) received physiotherapy for 3-6 weeks, and group III (n=40) received more than 6 weeks of physiotherapy. Physiotherapy consisted of 3 units per week. Each unit lasted for 30 min. All groups were compared statistically via variance analysis. RESULTS: Group I scored on average 88.8 points, group II 88.6 and group III 87.0 points. There were no statistically significant differences between the three groups (p=0.50). The age of patients had also no relevant influence on the outcome (p=0.48). CONCLUSIONS: Physiotherapy and age of the patients involved were not found to influence the outcome after open augmented repair of Achilles tendon ruptures followed by a standardised early rehabilitation. These results should be confirmed by a prospective randomised trial. Also elderly patients participating in demanding sport activities should receive a surgical repair.

[Evaluation of a strategy for the management of accompanying osteoporosis after inpatient treatment of fragility fractures]. / Analyse einer poststationären Behandlungsstrategie nach osteoporose-assoziierter Fraktur.

AIM: The aim of the present study was to evaluate a strategy for the management of accompanying osteoporosis after inpatient treatment of fragility fractures. METHOD: A prospective group of patients that was treated for acute fragility fractures between 9/05 and 2/06 was informed about a concomitant osteoporosis according to the national guidelines. Standardised letters with instructions for diagnostics and therapy for osteoporosis were given to patients, members of the family and outpatient care, rehab-clinic and GPs. Between 9/04 and 2/05 a retrospective review of a control group of patients with acute fragility fractures was conducted. This group was not informed about a concomitant osteoporosis. A telephone survey of all patients for analysis of the management of osteoporosis was conducted one year after clinical treatment. RESULTS: Both groups were comparable according to numbers of patients, age, distribution between the sexes and fracture localisation. The prospective group consisted of 144 patients. 29.9 % of these patients had already sustained a fragility fracture before treatment of the current fracture. In 45.8 % (32.6 % DEXA scans, 11.8 % Q CT, 1.4 % ultrasound) of the patients diagnostics were performed. A diagnosis of osteoporosis was documented in 42.4 % of the patients, and 57.1 % of the patients received specific treatments according to the guidelines. In the control group, 28.9 % of the patients had already sustained a fragility fracture before treatment of the current fracture. In 91.1 % of the patients no diagnostics for concomitant osteoporosis after clinical treatment for the acute fracture were performed within one year after fracture treatment. CONCLUSIONS: By use of a multifaceted osteoporosis intervention, more patients received diagnostics and therapy according to the guidelines of osteoporosis after fragility fractures. Without appropriate information, more than 60 % of the high-risk-patients did not receive adequate osteoporosis management. Future research should address barriers to appropriate osteoporosis management. Because of the chronic character of the disease and the necessity of a long-term therapy, continuous medical care and information of patients with osteoporosis is necessary to prevent subsequent fractures.

[Bilateral hip dislocation in cerebral palsy children: conservative therapy of the less affected hip and adductor tenotomy of the opposite hip]. / Beidseitige Hüftgelenksluxation bei infantiler Zerebralparese: konservative Therapie der weniger betroffenen Seite bei gegenseitiger Adduktorentenotomie.

AIM: In cerebral palsy children with bilateral hip dislocation, a new therapeutic concept was established that treated the less affected hip conservatively and the more affected hip simultaneously with an adductor tenotomy. The current study assessed whether the clinical and radiological outcome was equal to that of established bilateral surgical treatments. We also examined whether this approach leads to an adequate motor function improvement of the affected children. METHOD: In 41 children with cerebral palsy and bilateral hip dislocation, a prospective study assessed the hip abduction, migration percentage (MP) and the motor function (Rancho los Amigos scale). Depending on the pretherapeutic status, all patients were grouped into 3 abduction and 3 MP groups. The less affected hip was treated with a hip abduction splint whereas the more affected hip of the same child was simultaneously treated with a subcutaneous adductor tenotomy. All patients were assessed annually for 4 years. RESULTS: The hip abduction of the conservatively treated hips was pretherapeutically 41.8 +/- 2.6 degrees and improved significantly after 1 year. Patients with a pretherapeutic hip abduction < or = 20 degrees showed the most improvement. After 4 years, a significant deterioration of abduction was avoided in 49%. The pretherapeutic MP of the conservatively treated hips was 31.6 +/- 3.4% and was significantly but only slightly improved. The 4 year MP was significantly improved and the largest improvement was observed when the pretherapeutic MP was larger than 50%. A significant MP improvement after 4 years was achieved in 54%. After 4 years, 34% had undergone a motor function improvement. In 7% a motor function deterioration was observed. Posttherapeutically, the conservatively treated hips showed abduction and MP values that were comparable to those of surgically treated hip joints. CONCLUSION: In cerebral palsy children with bilateral hip dislocation, the conservative treatment of the less affected hip is suitable to achieve clinical and radiological results that are equal to the surgical treatment of the more affected hip. The concept of a combined conservative and surgical treatment of bilateral hip dislocation leads to an adequate motor function improvement that is comparable to established bilateral treatments.

[Prophylaxis and therapy for hip dislocations in patients with infantile cerebral palsy (ICP): motor functional, radiological and clinical results after subcutaneous adductor tenotomy]. / Prophylaxe und Therapie der Hüftgelenksluxation bei infantiler Zerebralparese (ICP): statomotorische, radiologische und klinische Ergebnisse nach subkutaner Adduktorentenotomie.

AIM: The current study assessed the clinical and radiological outcome and motor function improvement after subcutaneous adductor tenotomy in children with cerebral palsy (ICP). It was also analysed if groups with different preoperative hip functions and radiological hip migrations differed in their final clinical, radiological and motor function outcome. METHOD: A prospective study of 91 children with infantile cerebral palsy (ICP, mean age 4.9 years, range: 1.1 - 15.8) with 141 hip dislocations or subluxations analysed preoperatively the hip abduction and radiologically the migration percentage (MP). Depending on the preoperative status, all patients were grouped into 3 abduction and 3 MP groups. Additionally, the motor function was classified according to the Rancho los Amigos scale. A subcutaneous adductor tenotomy was performed mono- or bilaterally and all patients were treated for 4 - 6 weeks with a hip abduction splint. Patients were assessed annually for 4 years; clinical and radiological results and the motor function were analysed according to their preoperative status. RESULTS: The mean hip abduction was preoperatively 30.3 +/- 1.2 degrees and was significantly improved to 50.3 +/- 1.3 degrees 1 year and to 43.3 +/- 2.2 degrees 4 years post surgery. The preoperative mean MP was preoperatively 42.3 +/- 1.3 % and was significantly improved to 34.6 % 1 year and to 31.9 % 4 years post surgery. After 4 years, 41 % had undergone a motor function improvement and 52 % no change in motor function. After 4 years, patients with a hip abduction

[Bone tunnel fixation versus suture anchor: mid- and long-term results after distal biceps tendon rupture]. / Transossäre Refixation versus Fadenankerreinsertion, mittel- bis langfristige Ergebnisse nach distaler Bizepssehnenruptur.

AIM: The aim of this study was to assess the range of movement, isometric and isokinetic postoperative outcome, Morrey score and heterotropic ossifications after refixation of distal biceps tendon rupture with either suture anchor or bone tunnel fixation. METHODS: 48 patients were surgically treated between 1990 and 2005. Elbow function was investigated isometrically and isokinetically with the CYBEX-NORM. The presence and extent of heterotropic ossifications were assessed by A/P and lateral view X-rays. The Morrey score was used to evaluate the clinical outcome. RESULTS: 13 patients received distal biceps refixation with the bone tunnel method and 35 with suture anchors. The range of motion of the elbow was statistically not significantly different except for pronation, which was slightly but significantly reduced after bone tunnel refixation. Isometric and isokinetic results as well as Morrey scores were statistically not different between the two surgical techniques. Both groups showed excellent postoperative results. CONCLUSION: Bone tunnel and suture anchor techniques are both equal and sufficient methods for the refixation of distal biceps tendon ruptures with excellent clinical and functional postoperative results. The slight but significantly reduced pronation after bone tunnel refixation was clinically not relevant.

[Treatment of osteochondritis dissecans of the knee: one-step procedure with bone grafting and matrix-supported autologous chondrocyte transplantation]. / Einzeitige Rekonstruktion osteochondraler Defekte am Kniegelenk bei Osteochondrosis dissecans.

AIM: The aim of this study was to establish and assess a one-step reconstruction procedure of deep osteochondral defects of the knee joint with bone grafting and matrix-supported autologous chondrocyte transplantation in osteochondritis dissecans. METHOD: Between 2004 and 200622 patients with osteochondral defects in the weight-bearing zone of the femoral condyles(ICRS OCD III and IV) were reconstructed simultaneously with bone grafting and matrix-supported autologous chondrocyte transplantation (NOVOCART 3D). All patients were analysed prospectively. RESULTS: 17 Males and 5 females(age 28.3, range: 17-49 years) were surgically treated with the above-mentioned novel method. Before reconstruction osteochondral defects had an average defect area of 4.8 (2.4-9.0) cm2 and a depth of between 4 and 15 mm. For reconstruction an average of 2.6 (1-6) monocortical cancellous bone cylinders (diameter 8mm) was used to fill the osseous defect and to reconstruct the subchondral bone plate with adequate positioning of the monocortical layer of the graft. Then a Matrix-ACT was used to cover the reconstructed subchondral bone plate. The average follow-up was 16 (6-36) months. The average Tegner activity score was 4 (3-7) of 10. The Lysholm-Gillquistscore and the Cincinnati Sports Medicine and Orthopedic Center score were significantly improved postoperatively. The IKDC-2000 questionnaire was also significantly increased by 50%. CONCLUSION: The simultaneous reconstruction of deep osteochondral detects of the knee joint with bone grafting and matrix-supported autologous chondrocyte transplantation in osteochondritis dissecans is a biological, one-step alternative to previously reported methods with encouraging first results.

[T-plate osteosynthesis--an obsolete osteosynthesis procedure for proximal humeral fractures? Middle-term clinical and radiological results]. / Die T-Platten-Osteosynthese - ein überholtes Osteosyntheseverfahren für proximale Humerusfrakturen? Mittelfristige klinisch-radiologische Ergebnisse.

AIM: The present clinical trial was performed to assess the clinical and radiological outcome after operative treatment of proximal humeral fractures using the T-plate. METHODS: All patients who were treated with the T-plate were included into the study. Patient satisfaction,complications and radiological findings were assessed. The clinical results were evaluated using the Constant-Murley score, the UCLA score, and the DASH score. Between December 1996 and October 2003, 74 patients (with 76 fractures)were treated with the T-plate. Surgically treated complications were 2 hematomas and 3 failures of the osteosynthesis under functional physiotherapy. In 19 patients the implants were removed because of persisting complaints. RESULTS: After an average follow-up period of 67 months 52 patients (54 fractures) were examined. According to the Neer classification there were 34 2-part, 15 3-part and 5 4-part fractures.80% of the patients were satisfied with the result. According to the evaluated scores, 74 to 89% of the patients had an excellent to satisfactory outcome. CONCLUSION: The T-plate enables the stable fixation of complex proximal humeral fractures and permits even in the elderly patient an early functional treatment. Anatomical reconstruction and stable fixation followed by early rehabilitation are most important to achieve a good functional outcome in the patient.

[Bone tunnel fixation versus suture anchor: mid- and long-term results after distal biceps tendon rupture]. / Transossäre Refixation versus Fadenankerreinsertion, mittel- bis langfristige Ergebnisse nach distaler Bizepssehnenruptur.

AIM: The aim of this study was to assess the range of movement, isometric and is okinetic postoperative outcome, Morrey score and heterotropic ossifications after refixation of distal biceps tendon rupture with either suture anchor or bone tunnel fixation. METHODS: 48 patients were surgically treated between 1990 and 2005. Elbow function was investigated isometrically and isokinetically with the CYBEX-NORM. The presence and extent of heterotopic ossifications were assessed by A/P and lateral view X-rays. The Morrey score was used to evaluate the clinical outcome. RESULTS: 13 patients received distal biceps refixation with the bone tunnel method and 35 with suture anchors. The range of motion of the elbow was statistically not significantly different except for pronation, which was slightly but significantly reduced after bone tunnel refixation. Isometric and isokinetic results as well as Morrey scores were statistically not different between the two surgical techniques. Both groups showed excellent postoperative results. CONCLUSION: Bone tunnel and suture anchor techniques are both equal and sufficient methods for the refixation of distal biceps tendon ruptures with excellent clinical and functional postoperative results. The slight but significantly reduced pronation after bone tunnel refixation was clinically not relevant.

[Ankle chondrocytes are more resistant to Interleukin-1 than chondrocytes derived from the knee]. / Sprunggelenkchondrozyten besitzen eine höhere Interleukin-1-Resistenz als Kniegelenkchondrozyten.

BACKGROUND: The incidence of degenerative changes and osteoarthritis is lower in the ankle than in the knee joints. This cannot be explained exclusively with differences in anatomy and biomechanical properties of these two synovial joints. Previous studies have indicated distinct differences in the biochemical composition of the extracellular matrix of articular cartilage from knee and ankle joints. The aim of this study was to identify potential metabolic differences between knee and ankle joint chondrocytes using isolated cells to distinguish the secondary effects of the resident extracellular matrix from the primary matrix-independent effects of cellular differentiation. METHOD: Isolated knee and ankle chondrocytes from the same human donor were cultured in alginate beads and subsequently exposed to a three-day pulse of the catabolic cytokine interleukin-1 (IL-1) as a model of an inflammatory episode. The metabolism of proteoglycans (PG's) was analyzed as expressed changes in 35S-sulfate incorporation into glycosaminoglycans (GAG's). RESULTS: The presence of IL-1 induced an inhibition of PG synthesis in knee and ankle articular chondrocytes. The 50% inhibitory concentration (IC50) of IL-1 was about 5 times lower for knee than for ankle chondrocytes. CONCLUSION: Ankle chondrocytes are more resistant to IL-1 induced inhibition of PG synthesis than chondrocytes from the knee.

CD44H and the isoforms CD44v5 and CD44v6 in the synovial fluid of the osteoarthritic human knee joint.

OBJECTIVE: To determine whether the concentrations of CD44H and v5 and v6 in the synovial fluid are correlated with the presence of accompanying synovitis in the osteoarthritic joint and with the grade of osteoarthritis. DESIGN: Using antero-posterior and lateral X-rays of the knee joint and patellar view of 46 patients were graded with the Kellgren & Lawrence scale. Synovial fluid from these patients with different grades of primary osteoarthritis of the knee joint with and without synovial inflammation (synovitis) was collected during surgical procedures. A horseradish peroxidase conjugated anti-CD44H-, anti-sCD44v5- or anti-sCD44v6-antibody was added and labeled with tetramethylbenzidine. The absorbance was measured at wavelengths of 450/620 nm. Regression analysis was performed and the statistical significance was assessed, using the Student t-test for unequal variance. RESULTS: CD44H and v5 and v6 were detected in the synovial fluid of all 46 patients. Osteoarthritic patients with synovial inflammation showed significantly higher levels of CD44H and v6, but not v5, than osteoarthritic patients without synovial inflammation. With progression of osteoarthritis from Kellgren grade II to III, CD44v5 decreased significantly. All other isoform concentrations remained statistically unchanged. CONCLUSIONS: CD44H and the isoforms v5 and v6 were present in the synovial fluid of osteoarthritic patients. Their concentrations do not reflect the osteoarthritic stage in the Kellgren grading scale. CD44H and CD44v6, but not CD44v5, are significantly up-regulated in osteoarthritic synovial inflammation.