Association between patellar cartilage defects and patellofemoral geometry: a matched-pair MRI comparison of patients with and without isolated patellar cartilage defects.

PURPOSE: To compare the geometry of the patellofemoral joint on magnetic resonance images (MRI) between patients with isolated cartilage defects of the patella and a gender- and age-matched control group of patients without patellar cartilage defects. METHODS: A total of 43 patients (17 female, 26 male) with arthroscopically verified grade III and IV patellar cartilage defects (defect group) were compared with a matched-pair control group of patients with isolated traumatic rupture of the anterior cruciate ligament without cartilage defects of the patellofemoral joint. Preoperative MRI images were analysed retrospectively with regard to patellar geometry (width, thickness, facet angle), trochlear geometry (dysplasia according to Dejour, sulcus angle, sulcus depth, lateral condyle index, trochlea facet asymmetry, lateral trochlea inclination) and patellofemoral alignment (tibial tuberosity-trochlear groove distance, patella height, lateral patella displacement, lateral patellofemoral angle, patella tilt, congruence angle). In addition to the comparison of group values, the measured values were compared to normal values reported in the literature, and the frequency of patients with pathologic findings was compared between both groups. RESULTS: The defect group demonstrated a significantly higher proximal chondral sulcus angle (p < 0.001), a significantly higher distal osseal sulcus angle (p = 0.004), a significantly lower distal sulcus depth (p = 0.047), a significantly lower lateral condyle index (p = 0.045), a significantly lower Caton-Deschamps index (p = 0.020) and a significantly higher Insall-Salvati index (p = 0.010). A major trochlear dysplasia (grade B-D) was significantly more common in the defect group (54 vs. 19%; p < 0.001). Eighty-eight per cent of patients in the defect group demonstrated at least one pathologic finding, compared to 63% in the control group (p = 0.006). Two or more pathologic findings were observed in 42% of the defect group and in 19% of the control group (p = 0.019). There was no significant correlation between the localization of the chondral defects and the results of the measured parameters. CONCLUSIONS: Cartilage defects of the patella are associated with the geometry of the patellofemoral joint. In particular, a flat and shallow trochlea, trochlea dysplasia and patella alta seem to contribute to the development of patellar cartilage defects, which must be taken into consideration when planning to do surgical cartilage repair at the patella. LEVEL OF EVIDENCE: III.

Prospective clinical trial of patients who underwent ankle arthroscopy with articular diseases to match clinical and radiological scores with intra-articular cytokines.

OBJECTIVE: There is still a lack of reliable data on cytokine concentrations in the ankle and their value for prognosis. METHODS: In a prospective clinical trial, lavage fluids were collected from 49 patients with an arthroscopy of the ankle. The fluids were investigated by ELISA for cytokine levels. Clinical scores (FFI, AOFAS) were evaluated both pre-operatively and then again 12 months after surgery (n = 43, 88%). Radiological changes were noted with the Kellgren-Lawrence-Score (KLS) and the Ankle Osteoarthritis Scoring System (AOSS). Based on the difference between the pre- and postoperative clinical scores, two groups were defined according to whether they had benefited from the surgical therapy (Δ score ≥ 10) or not (Δ score < 10). RESULTS: The average clinical scores had improved to a statistically significant extent in the one-year follow-up (p < 0.01). BMP-2 (p = 0.02), IGF-1 (p = 0.04), BMP-7 (p = 0.01) and aggrecan (p = 0.04) showed significant correlations with pre-operative clinical and radiological scores (p = 0.02, p = 0.01, p = 0.01, p = 0.01). Furthermore, BMP-2 (p = 0.01), IGF-1/TPC (p = 0.03) and aggrecan (p = 0.01) correlated with scores after one year (p = 0.02, p = 0.01). High aggrecan concentrations were associated with a low clinical and a high radiological score at both time points, both indicating progress of cartilage degeneration in contrast to BMP-2 or IGF-1. Furthermore, MMP-13 concentrations were significantly higher in the non-benefit group (p = 0.02). CONCLUSION: BMP-2, IGF-1, aggrecan and MMP-13 seem to be involved in the degenerative process of cartilage in the ankle joint. Additionally, high synovial MMP-13 concentrations indicate a worse clinical outcome.

Correlation of synovial cytokine expression with quality of cells used for autologous chondrocyte implantation in human knees.

The cell quality plays a decisive role in autologous chondrocyte implantation (ACI). Aim of the study was the analysis of in vivo interactions between synovial concentrations of cytokines and cell quality used for ACI. Knee lavage fluids of patients undergoing an ACI were examined for total protein content (TPC) and by ELISA for levels of basic fibroblast growth factor (bFGF), insulin-like growth factor 1, bone morphogenetic proteins 2 and 7 (BMP-2 and BMP-7). Cell quality following amplification for ACI was determined by surface expression of CD44, aggrecan, collagen type II and evaluation of cell characteristics. Data of 17 patients were supplemented by epidemiological parameters and clinical scores (IKDC, Lysholm, pain strength, subjective knee function). CD44 expression was positively associated with TPC and bFGF, and negatively linked to BMP-2 levels (p < 0.01). In contrast, expression of collagen type II did not show any statistically significant correlations with synovial protein concentrations. TPC was positively associated with intraarticular bFGF levels and pain strength (p < 0.01), both indicators for osteoarthritis (OA). Correlating with the negative relation of TPC and BMP-2, subjective knee function after 1 year was positively linked to intraarticular BMP-2 concentrations (p < 0.001). Similarly, expression of collagen type II indicated a favorable clinical result reaching statistical significance in case of pain strength (p < 0.01). Initially increased bFGF levels and CD44 expression indicated a worse clinical outcome after 1 year (IKDC, Lysholm Scores, pain strength). Surface expression of CD44 on chondrocytes used for ACI was negatively associated with synovial BMP-2 and positively to TPC and bFGF indicating catabolic synovial conditions. These correlations were also reflected by clinical outcome parameters.

Expression of BMP-receptor type 1A correlates with progress of osteoarthritis in human knee joints with focal cartilage lesions.

BACKGROUND AIMS: Bone morphogenetic protein-2 (BMP-2) and its receptor type 1A (BMPR-1A) play significant roles in cartilage metabolism. The aim of this study was to evaluate a possible correlation between intra-articular expression of these proteins and the degree of osteoarthritis (OA) in human knees. METHODS: Biopsies of synovia and debrided cartilage were taken in 15 patients undergoing autologous chondrocyte implantation. Expression of BMP-2 and BMPR-1A was evaluated semi-quantitatively by immunohistologic staining. These data were complemented by grading of cartilage lesions according to International Cartilage Repair Society (ICRS), defect size, duration of complaints, knee osteoarthritis scoring system (KOSS) and Henderson and Kellgren-Lawrence scores. General histologic stainings were used to determine Mankin, Pritzker and Krenn scores. RESULTS: The expression of BMPR-1A but not of BMP-2 was significantly higher in cartilage biopsies taken in type 3 lesions with intact subchondral layer compared with type 4 defects (P < 0.05). In cartilage areas of bordering sectors, the intensity of immunohistologic staining of BMPR-1A was statistically significantly higher in mature cartilage compared with repair zones (P < 0.05). Expression of BMP-2 and its receptor 1A correlated in the cartilage biopsies (P < 0.02) but not in the synovia. The degree of OA was scored in all biopsies according to Mankin and Pritzker, and these scores correlated statistically significantly with BMPR-1A expression in the synovia (P < 0.05). In patients with an osteochondritis dissecans, the degree of OA was higher compared with other causes of chondromalacia, as evaluated by defect size, ICRS score, duration of complaints, Pritzker score and expression of BMPR-1A in cartilage (P < 0.05). CONCLUSIONS: These data support the role of BMPR-1A as an indicator of OA progression in human knees with circumscribed cartilage lesions.

Immunohistological localization of BMP-2, BMP-7, and their receptors in knee joints with focal cartilage lesions.

INTRODUCTION: Although it is well known that BMP-2 and BMP-7 play significant roles in cartilage metabolism, data about intra-articular expression and localization of these proteins and their receptors in humans are rare. METHODS: Biopsies of synovia and debrided cartilage were taken in patients undergoing autologous chondrocyte implantation. Expression of BMP-2, BMP-7, and their receptors BMPR-1A, BMPR-1B and BMPR-2 were semiquantitatively evaluated by immunohistological staining. RESULTS: BMP-7 was equally highly expressed in all cartilage and synovial biopsies. Increased levels of BMPR-1A, but not of BMPR-1B, and BMPR-2, were found in all synovial and 47% of all cartilage samples (P = 0.002). BMP-2 was positively scored in 47% of all cartilage and 40% of all synovial specimens. Defect size, KOSS, Henderson or Kellgren-Lawrence score did not statistically significant correlate with the expression of the analyzed proteins or Mankin and Pritzker scores. Duration of symptoms and localization of lesions were associated with KOSS (P < 0.02), but there was no influence of these parameters on protein expression. CONCLUSIONS: BMP-2, BMP-7, and BMPR-1A were expressed in cartilage and synovia of knees with focal cartilage lesions. Although defect localization and duration of symptoms decisively influence KOSS, there was no associated alteration of protein expression observed.

Anatomical Reconstruction of the Acromion Using an Autologous Iliac Crest Graft for Treatment of Recurrent Chondroblastoma: A Case Report.

CASE: A 38-year-old man presented with recurrent chondroblastoma of the acromion after primary curettage and bone grafting. The patient underwent revision surgery with resection of the acromion and reconstruction using an autologous iliac crest graft. He had regained normal shoulder function without recurrence at a follow-up of 17 months. CONCLUSIONS: This case demonstrates a rare location of chondroblastoma and successful anatomical and functional reconstruction. The described surgical procedure could be considered for large tumorous lesions of the acromion, for which curettage would be insufficient, and to preserve and reconstruct a functionally intact shoulder girdle.

Efficacy and Safety of Microsurgery in Interdisciplinary Treatment of Sarcoma Affecting the Bone.

Background: Sarcomas are tumors of mesenchymal origin with high variation in anatomical localization. Sarcomas affecting the bone often require an interdisciplinary resection and reconstruction approach. However, it is critical that microsurgical reconstruction strategies do not negatively impact tumor safety and overall survival, as limb salvage is only the secondary goal of tumor surgery. Here, we analyzed the efficacy and safety of microsurgery in interdisciplinary treatment of sarcoma affecting the bone. Patients and Methods: We performed a retrospective chart review of all patients treated for soft-tissue and bone sarcoma at the senior author's institution with a focus on bone affection and microsurgical reconstruction between 2000 and 2019. This particular subgroup was further investigated for tumor resection status, 5-year survival rate, length of hospital stay, as well as overall complication and amputation rates. Results: Between 2000 and 2019, 803 patients were operated for sarcoma resection and reconstruction by the Department of Plastic and Hand Surgery. Of these, 212 patients presented with sarcoma of the extremity affecting the bone. Within this subgroup, 40 patients required microsurgical reconstruction for limb salvage, which was possible in 38 cases. R0 resection was achieved in 93.8%. The 5-year survival was 96.7%, and the overall complication rate was 25%, of which 40% were microsurgery associated complications. Conclusion: Safe and function-preserving treatment of soft-tissue and bone sarcoma is challenging. Primary reconstruction with microsurgical techniques of sarcoma-related defects enables limb-sparing and adequate oncosurgical cancer treatment without increasing the risk for local recurrence or prolonged hospital stay. The treatment of sarcoma patients should be reserved to high-volume centers with experienced plastic surgeon embedded in a comprehensive treatment concept.

Associated tears of the lateral meniscus in anterior cruciate ligament injuries: risk factors for different tear patterns.

BACKGROUND: The pattern of lateral meniscus tears observed in anterior cruciate ligament (ACL)-injured subjects varies greatly and determines subsequent management. Certain tear patterns with major biomechanical consequences should be repaired in a timely manner. Knowledge about risk factors for such tears may help to identify patients in the early posttraumatic phase and subsequently may improve clinical results. METHODS: A database of 268 patients undergoing primary ACL reconstruction was used to identify all patients with isolated ACL tears and patients with an associated tear of the lateral meniscus. Patients who underwent surgery >6 months after the injury were excluded. Based on the arthroscopic appearance of the lateral meniscus, patients were assorted to one of three groups: 'no tear,' 'minor tear,' and 'major tear.' Tear patterns defined as major included root tears, complete radial tears, and unstable longitudinal tears including bucket-handle tears. Univariate analysis was performed by comparing the three groups with regard to gender, age, height, weight, BMI, type of injury (high-impact sport, low-impact sport, and not sports related), and mechanism of injury (non-contact vs. contact). Multivariate logistic regression was carried out to identify independent risk factors for minor and major meniscal tears and to calculate odds ratios (OR). RESULTS: Two hundred fifteen patients met the inclusion and exclusion criteria. Of those, 56% had isolated ACL tears, 27% had associated minor tears, and 17% had associated major tears of the lateral meniscus. Univariate analysis revealed significant differences between the three groups for gender (p = 0.002), age groups (p = 0.026), and mechanism of injury (p < 0.001). A contact injury mechanism was a risk factor for minor tears (OR: 4.28) and major tears (OR: 18.49). Additional risk factors for major tears were male gender (OR: 7.38) and age <30 years (OR: 5.85). CONCLUSION: Male patients, patients <30 years, and particularly patients who sustained a contact injury have a high risk for an associated major lateral meniscus tear. Special attention is therefore necessary in those patients and early referral to magnetic resonance imaging and/or arthroscopy is recommended to allow meniscus repair in a timely manner.

Development and retranslational validation of an in vitro model to characterize acute infections in large human joints.

Bacterial infections can destroy cartilage integrity, resulting in osteoarthritis. Goal was to develop an in vitro model with in vivo validation of acute joint inflammation. Inflammation in cocultivated human synovial fibroblasts (SFB), chondrocytes (CHDR), and mononuclear cells (MNC) was successively relieved for 10 days. Articular effusions from patients with (n = 7) and without (n = 5) postoperative joint infection in healthy patients (ASA 1-2) were used as model validation. Inflammation in vitro resulted in an enormous increase in IL-1 and a successive reduction in SFB numbers. CHDR however, maintained metabolic activity and proteoglycan synthesis. While concentrations of bFGF in vivo and in vitro rose consistently, the mRNA increase was only moderate. Concurring with our in vivo data, cartilage-specific IGF-1 steadily increased, while IGF-1 mRNA in the CHDR and SFB did not correlate with protein levels. Similarly, aggrecan (ACAN) protein concentrations increased in vivo and failed to correlate in vitro with gene expression in either the CHDR or the SFB, indicating extracellular matrix breakdown. Anabolic cartilage-specific BMP-7 with highly significant intra-articular levels was significantly elevated in vitro on day 10 following maximum inflammation. Our in vitro model enables us to validate early inflammation of in vivo cell- and cytokine-specific regulatory patterns. This trial is registered with MISSinG, DRKS 00003536.

Does form follow function in trochlear dysplasia? Case report of patellar instability in a below-knee amputee.

INTRODUCTION: Patellar instability can be considered as a rapidly increasing musculoskeletal subject of interest. It is now well accepted that multiple factors can produce this pathological condition, isolated, but more often in concert. One major static compound is found to be in trochlear dysplasia. It has been stated that the form of the trochlear surface is primary and genetically bilaterally determined already before use. According to these data, recurrent dislocation of the patella has been described as a hereditary disease with autosomal dominant transmission. Against this assumption, we hypothesize that subjects may devise a flattened trochlea when there is no significant biomechanical interplay and thus input between the patella and the distal femur during developmental growth; according to the assumption form follows function. PRESENTATION OF CASE: In this context, we report the case of a 16-year old male who previously suffered from a traumatic patellar dislocation during sporting activity in his below-knee amputated lower extremity, which occured at age of 18 months. The patient was allocated with a high-grade trochlear dysplasia in his previously amputated limb, while presenting a normal trochlear shape at his healthy contralateral leg. DISCUSSION: This rare case therefore reprents the history of an individuum with identic genetic predisposition and different biomechanical influences during childhood, which makes it of high clinical interest. In presence of trochlear dysplasia the patient suffered reluxation and concurrent subjective instability on the lower limb affected by the amputation which was treated with medial patellofemoral ligament (MPFL) plasty using an autologous gracilis graft. CONCLUSION: One has to consider that a certain biomechanical input may be required for the development of a physiologic trochlear groove.

Pain perception in knees with circumscribed cartilage lesions is associated with intra-articular IGF-1 expression.

BACKGROUND: Circumscribed cartilage defects are considered as prearthritic lesions and lead to differential intra-articular cytokine expression. Mechanisms of associated pain development and influence of smoking behavior are not yet fully understood in humans. PURPOSE: This study aimed to reveal relations between synovial cytokine levels in knees with circumscribed cartilage defects and pain sensation. STUDY DESIGN: Descriptive laboratory study. METHODS: In a clinical trial, knee lavage fluids of 42 patients with circumscribed cartilage lesions treated by either microfracturing (n = 19) or by autologous chondrocyte implantation (n = 23) and fluids of 5 healthy control individuals were prospectively collected. Preoperative knee pain was evaluated according to frequency and strength; subjective knee function was assessed using a visual analog scale and the International Knee Documentation Committee (IKDC) score. Synovial concentrations of aggrecan, insulin-like growth factor (IGF)-I, basic fibroblast growth factor (bFGF), interleukin (IL)-1ß, bone morphogenetic protein (BMP)-2, and BMP-7 were determined by enzyme-linked immunosorbent assay. RESULTS: Pain strength showed a highly significant association with intra-articular IGF-1 levels (ρ = .48, P < .01), but no correlation with synovial concentrations of aggrecan, bFGF, IL-1ß, BMP-2, and BMP-7. Although pain strength and frequency demonstrated a statistically significant relationship, no substantial association between pain frequency and any of the examined cytokine levels was found. Intra-articular IGF-1 concentrations significantly correlated with the area of cartilage damage (ρ = .35, P < .02); the other investigated cytokines failed to show this association. Neither of the determined intra-articular mediators demonstrated statistically significant correlations with subjective knee function or IKDC score. Only intra-articular concentrations of IGF-1 and BMP-2 statistically significantly correlated with age; total protein content was negatively associated with body mass index (P < .05). In smokers, synovial expression of total protein content, IGF-1, and bFGF was significantly diminished compared to nonsmokers (P < .05). CONCLUSION: Insulin-like growth factor-I is present in knees with circumscribed cartilage lesions in a size-dependent manner. IGF-1 levels correlated with indicators of pain perception; smoking negatively influenced synovial cytokine expression related to cartilage metabolism, but pain perception was not altered.

Volatile anesthetics induce caspase-dependent, mitochondria-mediated apoptosis in human T lymphocytes in vitro.

BACKGROUND: Volatile anesthetics modulate lymphocyte function during surgery, and this compromises postoperative immune competence. The current work was undertaken to examine whether volatile anesthetics induce apoptosis in human T lymphocytes and what apoptotic signaling pathway might be used. METHODS: Effects of sevoflurane, isoflurane, and desflurane were studied in primary human CD3 T lymphocytes and Jurkat T cells in vitro. Apoptosis and mitochondrial membrane potential were assessed using flow cytometry after green fluorescent protein-annexin V and DiOC6-fluorochrome staining. Activity and proteolytic processing of caspase 3 was measured by cleaving of the fluorogenic effector caspase substrate Ac-DEVD-AMC and by anti-caspase-3 Western blotting. Release of mitochondrial cytochrome c was studied after cell fractionation using anti-cytochrome c Western blotting and enzyme-linked immunosorbent assays. RESULTS: Sevoflurane and isoflurane induced apoptosis in human T lymphocytes in a dose-dependent manner. By contrast, desflurane did not exert any proapoptotic effects. The apoptotic signaling pathway used by sevoflurane involved disruption of the mitochondrial membrane potential and release of cytochrome c from mitochondria to the cytosol. In addition, the authors observed a proteolytic cleavage of the inactive p32 procaspase 3 to the active p17 fragment, increased caspase-3-like activity, and cleavage of the caspase-3 substrate poly-ADP-ribose-polymerase. Sevoflurane-induced apoptosis was blocked by the general caspase inhibitor Z-VAD.fmk. Death signaling was not mediated via the Fas/CD95 receptor pathway because neither anti-Fas/CD95 receptor antagonism nor FADD deficiency or caspase-8 deficiency were able to attenuate sevoflurane-mediated apoptosis. CONCLUSION: Sevoflurane and isoflurane induce apoptosis in T lymphocytes via increased mitochondrial membrane permeability and caspase-3 activation, but independently of death receptor signaling.