Adverse Tissue Reactions in Modular Exchangeable Neck Implants: A Report of Two Cases

Dual-modular femoral stems with exchangeable necks theoretically allow optimization of hip joint biomechanics via selective restoration of femoral anteversion, offset, and limb length. A potential disadvantage is the possible generation of metal ions and debris by fretting and crevice corrosion at the additional stem-neck interface. We present 2 cases of early-onset adverse inflammatory tissue reactions as a result of accelerated corrosion at the stem-neck interface of a dual-modular implant, requiring subsequent revision of well-fixed components.     

Monocytes and γδ T cells control the acute‐phase response to intravenous zoledronate: Insights from a phase IV safety trial

Aminobisphosphonates (NBPs) are used widely against excessive bone resorption in osteoporosis and Paget's disease as well as in metastatic bone disease and multiple myeloma. Intravenous NBP administration often causes mild to severe acute‐phase responses (APRs) that may require intervention with analgesics and antipyretics and lead to treatment noncompliance and nonadherence. We here undertook a phase IV safety trial in patients with osteoporosis to investigate the APR of otherwise healthy individuals to first‐time intravenous treatment with the NBP zoledronate. This study provides unique insight into sterile acute inflammatory responses in vivo, in the absence of confounding factors such as infection or cancer. Our data show that both peripheral γδ T cells and monocytes become rapidly activated after treatment with zoledronate, which ultimately determines the clinical severity of the APR. Our study highlights a key role for IFN‐γ in the zoledronate‐induced APR and identifies pretreatment levels of monocytes and central/memory Vγ9/Vδ2 T cells as well as their responsiveness to zoledronate in vitro as predictive risk factors for the occurrence of subclinical and clinical symptoms. These findings have diagnostic and prognostic implications for patients with and without malignancy and are relevant for Vγ9/Vδ2 T‐cell–based immunotherapy approaches. © 2012 American Society for Bone and Mineral Research. © 2013 American Society for Bone and Mineral Research.     

CD44 enhances tumor formation and lung metastasis in experimental osteosarcoma and is an additional predictor for poor patient outcome

Formation of metastases in the lungs is the major cause of death in patients suffering from osteosarcoma (OS). Metastases at presentation and poor response to preoperative chemotherapy are strong predictors for poor patient outcome. The elucidation of molecular markers that promote metastasis formation and/or chemoresistance is therefore of importance. CD44 is a plasma membrane glycoprotein that binds to the extracellular matrix component hyaluronan (HA) and has been shown to be involved in metastasis formation in a variety of other tumors. Here we investigated the role of CD44 expression on OS tumor formation and metastasis. High CD44 expression, evaluated with a tissue microarray including samples from 53 OS patients and stained with a pan‐CD44 antibody (Hermes3), showed a tendency (p < 0.08) to shortened overall survival. However, nonresponders and patients with lung metastases and high CD44 expression had significantly poorer prognosis than patients with low CD44 expression. Overexpression of the standard CD44 isoform (CD44s) and its HA‐binding defective mutant R41A in osteoblastic SaOS‐2 cells resulted in HA‐independent higher migration rates and increased chemoresistance, partially dependent on HA. In an orthotopic mouse model of OS, overexpression of CD44s in SaOS‐2 cells resulted in an HA‐dependent increased primary tumor formation and increased numbers of micrometastases and macrometastases in the lungs. In conclusion, although CD44 failed to be an independent predictor for patient outcome in this limited cohort of OS patients, increased CD44 expression was associated with even worse survival in patients with chemoresistance and with lung metastases. CD44‐associated chemoresistance was also observed in vitro, and increased formation of lung metastases was found in vivo in SCID mice. © 2013 American Society for Bone and Mineral Research.     

Enhanced migration of human bone marrow stromal cells in modified collagen hydrogels

Purpose

Collagen I hydrogels are widely used as scaffolds for regeneration of articular cartilage defects. We hypothesised that ingrowth might be improved by removing the superficial layer of a compressed hydrogel. The control group consisted of the original unmodified product.

Methods

The migration of human bone marrow stromal cells (hBMSCs) into the hydrogel was evaluated by confocal microscopy. We quantified the DNA concentration of the hydrogel for each group and time point and evaluated the chondrogenic differentiation of cells.

Results

After one week, the detectable amount of cells at the depth of 26–50 μm was significantly higher in the modified matrix (MM) than in the non-modified matrix (NM) (p = 0.011). The maximum depth of penetration was 75 μm (NM) and 200 μm (MM). After three weeks, the maximum depth of penetration was 175 μm (NM) and 200 μm (MM). Likewise, at a depth of 0–25 μm the amount of detectable cells was significantly higher in the MM group (p = 0.003). After 14 days, the concentration of DNA was significantly higher in the samples of the MM than in the control group (p = 0.000). Staining of histological sections and labelling with collagen II antibodies showed that a chondrogenic differentiation of cells in the scaffold can occur during in vitro cultivation.

Conclusions

Removing the superficial layer is essential to ensuring proper ingrowth of cells within the compressed hydrogel. Compressed hydrogels contribute better to cartilage regeneration after surface modification.     

Indications for and results of arthroscopy in the arthritic knee: a European survey

Purpose

The place of arthroscopic treatment in osteoarthritis of the knee has generated much controversy. A survey was initiated to collect the opinion of experienced surgeons.

Methods

Of the 211 surgeons interviewed, 170 (80.6 %) replied to the electronic questionnaire. Respondents had at least ten years of experience in arthroscopy and currently perform more than 100 arthroscopies per year. Various indications and treatment modalities for arthroscopy in osteoarthritis of the knee had to be evaluated on a scale from “excellent” to “no indication”.

Results

The respondents generally believe that an improvement is more likely in low-grade osteoarthritis (p < 0.001) and in neutral leg axis (p < 0.001). The outcome was rated better if symptoms had persisted for less than six months (p < 0.001) and for patients that were younger than 60 years (p < 0.001). Partial meniscectomy and notchplasty in cases of extension deficit were considered as successful treatment options. Debridement was an accepted indication, with an outcome mainly rated as fair. A majority saw no indication for joint lavage, arthroscopic treatment of arthrofibrosis and removal of osteophytes. The outcome appears to be poor if a bone edema is diagnosed on magnetic resonance imaging prior to arthroscopy. Only 55.9 % of respondents were comfortable with the current definition of osteoarthritis.

Conclusions

Experienced arthroscopic surgeons all over Europe believe arthroscopy in osteoarthritis is appropriate, under certain conditions. The major task for surgeons is to select the right patients who are likely to benefit from this intervention.     

Sports activities after medial unicompartmental knee arthroplasty Oxford III—What can we expect?

Purpose

Excellent long-term results have been reported for implantation of unicompartmental knee arthroplasty (UKA). In many patients the desire for improvement in function often includes an aspiration to return to sports. The purpose of our study was to evaluate physical activities after medial Oxford-III (Biomet) UKA surgery.

Methods

Patients’ physical activity before and after the surgery was assessed using a self reporting questionnaire. We used the Oxford knee scoring system (OKS), the WOMAC-, the Knee society- (KSS) and the UCLA-score to assess postoperative knee function. The mean follow-up was 4.2 years. The female-to-male ratio was 1.3:1. The mean age at surgery was 65.3 years.

Results

Of the 131 patients studied 78 participated in some kind of sports before surgery (mean age 64.4 years), while 53 patients did not perform any sports (mean age 66.5 years) (p > 0.05). At follow-up the patients in the active group were significantly younger than the patients in the inactive group (p < 0.05). The majority of patients (80.1 %) returned to their level of sports activity after UKA surgery. Six patients took up sports after surgery while 15 patients stopped their sports. Among the active patients we found a shift from high- towards low-impact sports. The active patients had significantly higher scores for the OKS, KSS, WOMAC and UCLA score. The complication rate was comparable in both groups.

Conclusion

Our study demonstrates that a high degree of patient satisfaction in terms of sports activity can be achieved using the Oxford-III UKA for medial osteoarthritis.     

Surgical resection and radiation therapy of desmoid tumours of the extremities: results of a supra-regional tumour centre

Purpose

Desmoid tumours of the extremity have a high recurrence rate. The purpose of this study was to analyse the outcome after resection of these tumours with special emphasis on recurrent disease and adjuvant therapeutic strategies.

Methods

In this retrospective study we evaluated prognostic factors for recurrence-free survival after surgical treatment of desmoid tumours of the extremity in 27 patients with an average age of 41 years treated from 1997 to 2009. Adjuvant radiotherapy (50–60 Gy) was given in five cases with primary and in nine patients with recurrent disease. The average follow-up was 64 months.

Results

The five-year recurrence-free survival in patients with primary disease was 33 %. Patients with negative resection margins tended to have a better outcome than patients with positive resection margins, but the difference between both groups was not significant (56 vs 14 %, p = 0.145). In patients with positive margins, adjuvant radiotherapy did not significantly improve recurrence-free survival (40 vs 14 %, p = 0.523). Patients with local recurrence had a five-year further recurrence-free survival of 47 %. In those patients further recurrence-free survival was significantly better after adjuvant radiation (89 vs 25 %, p = 0.015). Two thirds of all patients suffered moderate or severe complications due to the treatment regimen.

Conclusions

Compared to desmoids of the trunk or the head and neck region, desmoids affecting the limbs show by far the worst outcome in terms of relapse or treatment-related morbidity. The importance of negative resection margins is still not clear. Particularly in recurrent desmoids adjuvant radiotherapy appears to reduce the further recurrence rate. Therefore, a general use of radiation should be considered for this high-risk group.