A randomized controlled trial demonstrating sustained benefit of autologous matrix-induced chondrogenesis (AMIC®) over microfracture: 10-year follow-up.

PURPOSE: Autologous matrix-induced chondrogenesis (AMIC®) and microfracture are established treatments for focal chondral defects in the knee, but there are little clinical data concerning these procedures over the long term. This study evaluates the outcomes of AMIC® compared to microfracture over 10-year follow-up. METHODS: Forty-seven patients were randomized and treated either with MFx (n = 13), sutured AMIC® (n = 17) or glued AMIC® (n = 17) in a prospective, randomized, controlled multicentre trial. The Modified Cincinnati Knee Score, a visual analogue scale for pain and MOCART score were used to assess outcomes over 10 years post-operatively. RESULTS: All treatment arms improved in the first 2 years, but a progressive and significant deterioration in scores was observed in the MFx group, while both AMIC® groups remained stable. MOCART scores were comparable between groups. CONCLUSION: The AMIC® procedure results in improved patient outcomes in comparison with microfracture up to 10 years following surgery for the repair of focal chondral defects in the knee. CLINICALTRIALS: gov Identifier: NCT02993510.

A randomized controlled trial demonstrating sustained benefit of Autologous Matrix-Induced Chondrogenesis over microfracture at five years.

PURPOSE: Autologous Matrix-Induced Chondrogenesis (AMIC®) utilizing a type I/III collagen membrane was compared with microfracture (MFx) alone in focal cartilage lesions of the knee at one, two and five years. METHODS: Forty-seven patients (aged 37 ± 10 years, mean defect size 3.6 ± 1.6 cm2) were randomized and treated either with MFx, with sutured or glued AMIC® in a prospective multicentre clinical trial. RESULTS: After improvement for the first two years in all subgroups, a progressive and significant score degradation was observed in the MFx group, while all functional parameters remained stable for least five years in the AMIC® groups. At two and five years, MRI defect filling was more complete in the AMIC® groups. No treatment-related adverse events were reported. CONCLUSIONS: AMIC® is an effective cartilage repair procedure in the knee resulting in stable clinical results significantly better than the MFx group at five years.

Appropriate sagittal femoral component alignment cannot be ensured by intramedullary alignment rods.

PURPOSE: The intraoperative sagittal cutting block alignment when intramedullary alignment rods are used was investigated. Its absolute orthogonal orientation in relation to the mechanical femoral axis should be analysed. It was hypothesized that (1) alignment rods do not ensure a desired deviation within a range between 0° and 3° flexion as it has been shown to be favourable for clinical and functional outcome. Further, the degree of flexion cannot be (2) foreseen by the surgeon or (3) estimated by clinical or radiological parameters. METHODS: Forty knees allocated to total knee arthroplasty were included. The distal femoral cutting block was aligned using an intramedullary rod. By means of a navigation device, the sagittal alignment of the cutting block in degrees of flexion was measured. RESULTS: The mean measured flexion of the cutting block was 4.4° (3.6 SD). Twenty-five per cent (10/40) of the values were within a corridor between 0° and 3° of flexion. The mean difference between expected and measured flexion was -1.5° (-7.6 to 4.7 95 % limits of agreement). The dorsoventral diameter of the distal femur showed a significant influence on measured flexion (R (2) = 0.112, p = 0.035). CONCLUSION: Intramedullary alignment rods used in the present study do not ensure a distal cutting block alignment between 0° and 3° of flexion in relation to the femoral mechanical axis. The extent of flexion could not be foreseen either by the surgeon. The dorsoventral diameter of the distal femur correlated with measured flexion. However, only limited data is available on influence of femoral component flexion on implant failure or clinical and functional outcome. LEVEL OF EVIDENCE: Diagnostic study, Level II.

Pinless navigation in total knee arthroplasty: navigation reduced by the maximum?

PURPOSE: Restoring a neutral mechanical axis in total knee arthroplasty (TKA) (within ±3° of varus/valgus) is associated with superior functional outcome and reduced early implant failure. Using conventional alignment jigs results in malalignment in >20 % of cases. In this study, we investigated the reduction of outliers within the threshold of ±3° of leg alignment using a "pinless" navigation system in comparison with conventional alignment jigs investigated. METHODS: In this randomised prospective study, 80 patients were randomly assigned/allocated to the pinless or conventional control group. After surgery, the two groups were compared regarding outliers > ±3° by means of hip-knee-ankle angle (HKA), mechanical medial proximal tibia angle (mMPTA), mechanical lateral distal femoral angle (mLDFA) and duration of surgery. Student's unpaired t test was used for quantitative variables, Fisher's exact test compared groups (pinless vs. control) and a two-sided p value of ≤0.05 was considered statistically significant. RESULTS: In the pinless group, outliers regarding HKA and mLDFA > ±3° was significantly reduced (p = 0.025 and p = 0.002 respectively). In the pinless group, the surgery duration was significantly longer (75.6 vs. 64.5 minutes, p < 0.001). CONCLUSION: Pinless navigation is effective in reducing outliers > ±3° regarding HKA without risking pin-related complications, such as fractures, infections or breaking screws. However, not all tools for conventional navigation in TKA, such as real-time measurements of the tibiofemoral axis and gap balancing, are available.

The influence of component alignment on patellar kinematics in total knee arthroplasty.

BACKGROUND AND PURPOSE: Postoperative anterior knee pain is one of the most frequent complications after total knee arthroplasty (TKA). Changes in patellar kinematics after TKA relative to the preoperative arthritic knee are not well understood. We compared the patellar kinematics preoperatively with the kinematics after ligament-balanced navigated TKA. PATIENTS AND METHODS: We measured patellar tracking before and after ligament-balanced TKA in 40 consecutive patients using computer navigation. Furthermore, the influences of different femoral and tibial component alignment on patellar kinematics were analyzed using generalized linear models. RESULTS: After TKA, the patellae shifted statistically significantly more laterally between 30° and 60°. The lateral tilt increased at 90° of flexion whereas the epicondylar distance decreased between 45° and 75° of flexion. Sagittal component alignment, but not rotational component alignment, had a significant influence on patellar kinematics. INTERPRETATION: There are major differences in patellar kinematics between the preoperative arthritic knee and the knee after TKA. Combined sagittal component alignment in particular appears to have a major effect on patellar kinematics. Surgeons should be especially aware of altering preoperative sagittal alignment until the possible clinical relevance has been investigated.

Predicting knee rotation by the projection overlap of the proximal fibula and tibia in long-leg radiographs.

PURPOSE: Rotation of the lower limbs in long-leg radiographs has a significant impact on imaging the mechanical femorotibial angle, the femoral anatomic mechanical angle, the mechanical lateral distal femoral angle (mLDFA) and the mechanical medial proximal tibial angle (mMPTA). In this study, we assessed the rotation of the lower limbs in conventional radiographs and hypothesized that the relative position of the proximal fibula to the proximal tibia on long-leg radiographs is related to the rotation of the knee joint. METHODS: Radiological examinations in different rotational positions of the knee joint (incremental 40° internal to 40° external rotation) were imitated by 50 computed tomography scans (50 patients, 25 men and 25 women). The extent of the projection overlaps of the fibula, the fibular tip and the distance from the fibular tip to the lateral cortex were determined for every rotational position. RESULTS: Multiple regression analysis showed a very strong correlation between the measured fibular parameters and knee rotation between 20° of internal rotation and 40° of external rotation (R (2) ~ 0.94, p < 0.001). By means of these results, we created a formula for predicting knee rotation: [Formula: see text]This strong correlation could not be found between 20° and 40° of internal rotation. DISCUSSION: Because incorrect internal and external rotation negatively influence the correct measurement of angles (mechanical femorotibial angle, femoral anatomic mechanical angle, the mLDFA and the mMPTA), long-leg radiographs should be assessed for proper rotation angles before measurement. Using the provided formula rotation of the lower limb in weight-bearing, long-leg radiographs can be reliably predicted. LEVEL OF EVIDENCE: Diagnostic study, Level II.

Accuracy of bony landmarks for restoring the natural joint line in revision knee surgery: an MRI study.

PURPOSE: Restoring the joint line (JL) improves clinical and functional outcome in total knee arthroplasty (TKA). Therefore, anatomical landmarks to approximate the JL have been published. So far, the natural deviation of the JL 90° to the mechanical tibial axis has not been considered. Thus, we designed this study to: (1) determine the natural JL of knees in healthy persons in respect to the mechanical tibial axis, (2) validate and double-check intra-operative bony landmarks already been published in respect to the natural JL and (3) find possible correlations between distances from bony landmarks to the JL and femoral and tibial width. METHODS: Eighty MRI scans of knees of healthy persons were examined by two independent observers. Distances from the tip of the fibular head (FH), the medial (ME) and lateral (LE) epicondyles and the adductor tubercle (AT) to the JL within the medial and lateral compartment were measured. Further, we determined the orientation of the JL in respect to the mechanical axis of the tibia. Interobserver correlations were calculated. Differences were analyzed using Student's t test. Linear regression models were calculated to analyze correlations. RESULTS: Interobserver correlation was excellent. Mean JL deviation was 4.2° varus. Distance between the FH, ME, LE and AT to the JL within the medial compartment was 12.2, 33.9, 33.4 and 45.4 mm, respectively. Within in the lateral compartment, distances were 15.3, 31.0, 30.6 and 42.3 mm to the JL. Strong correlation was found between femoral width and distances from the AT, ME and LE to the JL. CONCLUSION: In TKA, the JL is usually altered due to the classic resection technique, which does not respect the natural deviation of the JL. Estimating the natural JL by adding absolute values to bony landmarks, as proposed in the literature, is not recommended. According to our data, the JL can be best estimated by adding the calculated value: 6.40 + (width femur [mm] × 0.49) to the AT.

Bisphosphonates or prostacyclin in the treatment of bone-marrow oedema syndrome of the knee and foot.

Bone-marrow oedema (BME) represents a reversible but mostly painful increase in interstitial fluid. The exact pathogenetic processes still remain unknown. Treatment options are mainly symptomatic with core decompression as golden standard leading to immediate pain relieve. Recently, it has been shown that intravenous prostacyclin and bisphosphonates are useful in achieving a reduction in BME with a considerable improvement in the accompanying symptoms. We compared the outcome of both intravenously applied prostacyclin (Ilomedin(®), 10 patients) and bisphosphonate (Bondronat(®), 10 patients) in treatment of BME of the knee and foot. We could find a significant improvement of WOMAC score, SF-36 score and VAS 3 months and 1 year after therapeutic intervention in both the prostacyclin and the bisphosphonate group. Concerning the MRI scans in both groups, we found a distinct reduction of BME in 47 % and a complete regression in 40 %. Comparing both groups, the improvement of the scores was greater in the prostacyclin group than in the bisphosphonate group; the difference, however, was not significant. Intravenous bisphosphonates as well as prostacyclin are of efficient therapeutic benefit in treatment of BME with a quicker and greater effect of prostacyclin.

Infusion, core decompression, or infusion following core decompression in the treatment of bone edema syndrome and early avascular osteonecrosis of the femoral head.

An increase in interstitial fluid is an expression of bone marrow edema (BME) and osteonecrosis (ON). The exact pathogenetic processes still remain unknown. Treatment options are mainly symptomatic with core decompression as surgical golden standard with immediate pain relief. Recently, it has been shown that intravenous iloprost can be used to achieve a reduction in BME and ON with a considerable improvement in the accompanying symptoms. The effect of intraveneously applied iloprost alone (12 patients) was studied against core decompression alone (12 patients) as well as iloprost following core decompression (12 patients). We could find a significant improvement in HHS, WOMAC score, SF-36 score and VAS 3 months and 1 year after therapeutical intervention in all treatment groups; however, statistically best results were obtained by combination. Concerning the MRI scans, we found a distinct reduction in BME in all groups again favoring the combination. Concerning ON, the results were not as promising as for BME. Intravenous prostacyclin and core decompression as monotherapy are of efficient therapeutical benefit in the treatment of BME, and the combination of both methods, however, seems to be most promising, also in the treatment of ON. Long-term results and higher number of patients are needed for final statements.

Assessing patient-oriented results after revision total knee arthroplasty.

BACKGROUND: Revision total knee arthroplasties (TKA) have been performed with increasing frequency over the last 25 years. METHODS: In this study, we retrospectively analyzed 78 patients who underwent 78 revision TKAs during the years 2003­2007 with an average follow-up of 81 months (range 60­108 months). All patients were treated with a standard rotating hinge prosthesis (TC3, DePuy, Warsaw, IN, USA) due to significant instability. We evaluated the postoperative results using the Knee Society clinical rating system and the WOMAC rating system. RESULTS: Clinical results revealed significant improvements in both scores. Complications occurred in almost one-third of the cases, with a reoperation rate of 26 %. CONCLUSION: Our mid-term findings show that revision TKAs lead to an improvement in patient-perceived outcomes of physical variables. While revision TKA is a useful option for patients, procedure-associated complications should not be neglected. During the course of the procedure, it is important to collect patient-oriented data and focus on responsive and valid scores.

Comparing navigation-based in vivo knee kinematics pre- and postoperatively between a cruciate-retaining and a cruciate-substituting implant.

PURPOSE: Individual physiological knee kinematics are highly variable in normal knees and are altered following cruciate-substituting (PS) and cruciate-retaining (CR) total knee arthroplasty (TKA). We wanted to know whether knee kinematics are different choosing two different knee designs, CR and PS TKA, during surgery using computer navigation. METHODS: For this purpose, 60 consecutive TKA were randomised, receiving either CR (37 patients) or PS TKA (23 patients). All patients underwent computer navigation, and kinematics were assessed prior to making any cuts or releases and after implantation. Outcome measures were relative rotation between femur and tibia, measured medial and lateral gaps and medial and lateral condylar lift-off. RESULTS: We were not able to demonstrate a significant difference in femoral external rotation between either group prior to implantation (7.9° CR vs. 7.4° PS) or after implantation (9.0° CR vs. 11.3° PS), both groups showed femoral roll-back. It significantly increased pre- to postoperatively in PS TKA. In the CR group both gaps increased, the change of the medial gap was significantly attributable to medial release. In the PS group both gaps increased and the change of the medial and of the lateral gap was significant. Condylar lift-off was observed in the CR group during 20° and 60° of flexion. CONCLUSION: This study did not reveal significant differences in navigation-based knee kinematics between CR and PS implants. Femoral roll-back was observed in both implant designs, but significantly increased pre- to postoperatively in PS TKA. A slight midflexion instability was observed in CR TKA. Intra-operative computer navigation can measure knee kinematics during surgery before and after TKR implantation and may assist surgeons to optimise knee kinematics or identify abnormal knee kinematics that could be corrected with ligament releases to improve the functional result of a TKR, whether it is a CR or PS design. Our intra-operative finding needs to be confirmed using fluoroscopic or radiographic 3D matching after complete recovery from surgery.

Chemical synovectomy with sodium morrhuate in the treatment of symptomatic recurrent knee joint effusion.

The aim of this study was to assess the efficacy and safety of intra-articular sodium morrhuate injections in the treatment of recurrent knee joint effusions. Ninety-eight knees of 92 patients (f = 59, m = 33) with knee arthritis of heterogeneous etiology were treated with chemical synovectomy (CSO). Of those, 39 patients suffered from rheumatoid arthritis (RA). The mean follow-up was 29.8 months. Clinical outcome was evaluated by analyzing subjective patient satisfaction, activity level, pain severity on the basis of the Visual Analogue Pain Scale (VAS), Lysholm and Gillquist score, and the Knee Injury and Osteoarthritis Outcome Score (KOOS). Fifty-seven percent of all patients and 67% of patients diagnosed with RA were satisfied with CSO. No significant effects on patient satisfaction by CSO were noted in patients older than 40 years. Overall, VAS, Lysholm and Gillquist score, and KOOS improved significantly at final review. The intra-articular application of sodium morrhuate is an effective and safe measure in the treatment of recurrent symptomatic knee joint effusions in young patients suffering from recurrent knee joint effusions.

Treatment of deep articular talus lesions by matrix associated autologous chondrocyte implantation--results at five years.

PURPOSE: Treatment of focal full-thickness chondral or osteochondral defects of the talus remains a challenge. The aim of this study was to evaluate the postoperative success and the long-term efficacy of matrix associated autologous chondrocyte implantation in these defects. METHODS: Matrix associated autologous chondrocyte implantation (MACI) was applied in 22 consecutive patients (mean age 23.9 years) with full-thickness chondral or osteochondral lesions of the talus. The average defect-size was 1.94 cm² (range 1-6). In case of osteochondritis dissecans (n = 13) an autologous bone graft was performed simultaneously. Follow-ups were routinely scheduled up to 63.5 (±7.4) months, consisting of clinical evaluation and magnetic resonance imaging. RESULTS: The AOFAS score improved significantly from 70.1 to 87.9/92.6/93.5/95.0/95.5 and 95.3 points at three, six, 12, 24, 36 and 63.5 months, respectively. On a visual analogue scale, pain intensity decreased from 5.7 (±2.6) to 0.9 (±0.8) while subjective function increased from 5.3 (±2.3) to 8.9 (±0.9) at final follow-up (each p < 0.001). The Tegner score rose significantly from 2.4 (±1.2) to 4.7 (±0.6). The MOCART score improved from 62.6 (±19.4) at three months to 83.8 (±9.4) at final follow-up. No significant differences were found between lesions caused by osteochondritis dissecans or trauma and between first- or second-line treatments. For all scores, the most benefit was seen within the first 12 months with stable results afterwards. No major complications were noted. CONCLUSIONS: Matrix associated autologous chondrocyte implantation is capable of significant and stable long-term improvement of pain and functional impairment caused by focal full-thickness chondral and osteochondral talus lesions.

Fluoroscopy-guided retrograde core drilling and cancellous bone grafting in osteochondral defects of the talus.

PURPOSE: In undetached osteochondral lesions (OCL) of the talus both revitalisation of the subchondral necrosis and cartilage preservation are essential. For these cases, we assess the results of minimally invasive retrograde core drilling and cancellous bone grafting. METHODS: Forty-one osteochondral lesions of the talus (12x grade I, 22x grade II and 7x grade III according to the Pritsch classification, defect sizes 7-14 mm) in 38 patients (mean age 33.2 years) treated by fluoroscopy-guided retrograde core drilling and autologous cancellous bone grafting were evaluated by clinical scores and MRI. The mean follow-up was 29.0 (±13) months. RESULTS: The AOFAS score increased significantly from 47.3 (±15.3) to 80.8 (±18.6) points. Lesions with intact cartilage (grades I and II) had a tendency to superior results than grade III lesions (83.1 ± 17.3 vs. 69.4 ± 22.2 points, p = 0.07). First-line treatments and open distal tibial growth plates led to significantly better outcomes (each p < 0.05). Age, gender, BMI, time to follow-up, defect localisation or a traumatic origin did not influence the score results. On a visual analogue scale pain intensity reduced from 7.5 (±1.5) to 3.7 (±2.6) while subjective function increased from 4.6 (±2.0) to 8.2 (±2.3) (each p < 0.001). In MRI follow-ups, five of the 41 patients showed a complete bone remodelling. In two cases demarcation was detectable. CONCLUSIONS: The technique reported is a highly effective therapeutic option in OCL of the talus with intact cartilage grades I and II. However, second-line treatments and grade III lesions with cracked cartilage surface can not be generally recommended for this procedure.

Arthrodesis of the talonavicular joint using angle-stable mini-plates: a prospective study.

PURPOSE: The talonavicular joint is a central connection of the human foot. Symptomatic talonavicular arthritis can be adequately addressed by isolated talonavicular fusion. However, non-union remains a relevant clinical challenge to the orthopaedic surgeon. The aim of this study was to analyse the clinicoradiological outcome of talonavicular fusion using angle-stable mini-plates. METHODS: We performed 30 talonavicular fusions in 30 patients (12 male, 18 female) with a mean age of 58.8 years (range, 22-74) between 2005 and 2007. Osseous joint fusion was achieved using mono- and multidirectional angle-stable mini-plates. The patients followed a standardised immobilisation and weight bearing protocol. The mean postoperative follow up was 15.8 months (6.1-23.8). RESULTS: The American Orthopedic Foot and Ankle Society AOFAS score increased significantly from 31.7 (19-42) to 82.3 points (55-97) (p < 0.001). Neither age at operation nor gender influenced the score results significantly, while the aetiology of talonavicular degeneration showed a significant effect. Mean visual analogue scale (VAS) pain intensity (0-10) reduced from 8.6 to 1.7 (p < 0.001). Good or excellent results were achieved in 26 patients, while two patients reported fair and another two poor results. Complete osseous fusion was observed at a mean of 10.9 weeks (8-13) postoperatively. CONCLUSIONS: For the treatment of talonavicular arthritis, the application of mono- and multidirectional angle-stable mini-plates provided a strong fixation that led to high union rates and good to excellent overall outcome.

Clinical outcome after Chevron-Akin double osteotomy versus isolated Chevron procedure: a prospective matched group analysis.

BACKGROUND: Hallux valgus is a frequent condition of the forefoot, resulting in cosmetic deformity and pain. Chevron osteotomy (CO) is widely employed for the treatment of hallux valgus. Chevron-Akin double osteotomy (CAO) was previously described and superiority over an isolated Chevron procedure was assumed. The objective of this study was to compare the short-to-middle term outcomes of CO and CAO. PATIENTS AND METHODS: This study included 72 patients with established diagnosis of mild-to-moderate hallux valgus, treated by either isolated CO or CAO. The CO group included 46 patients (mean 51.5 years) with a mean hallux valgus angle of 27°, while the CAO group included 26 subjects (mean 53.1 years) and a mean hallux valgus angle of 32° preoperatively. All patients were reviewed by physical examination, and standardized questionnaire, and pre- and postoperative standing X-rays were performed. Matched group analysis was carried out to analyze statistical differences of both techniques. RESULTS: The patients were assessed and group matched at a mean of 1.37 years for the CO group and 1.04 years for the CAO group, postoperatively. Mean improvement of HVA (hallux valgus angle) was 10.6° in the CO group and the CAO group improved by 17.5°. DMAA (distal metatarsal articular angle) improved in the CO group by 5.4° and in the CAO by 13.7°. Mean AOFAS score improved by 27.9 (CO) and 21.5 (CAO). Patient satisfaction was high in both groups, with a tendency towards higher values within the CAO group. CONCLUSIONS: These findings indicate that Chevron-Akin double osteotomy is a save and practicable procedure for the treatment of mild-to-moderate hallux valgus. Superiority of combined Chevron-Akin procedure over an isolated Chevron osteotomy might be limited to distinct clinical settings, but should not be generally assumed.

In vivo knee kinematics of an innovative prosthesis design.

Up to 20% of patients after total knee arthroplasty (TKA) are not satisfied with the result. Several designs of new implants try to rebuild natural knee kinematics. We hypothesized that an innovative implant design leads to better results concerning femoral rollback compared to an established implant design. For this pilot study, 21 patients were examined during TKA, receiving either an innovative (ATTUNETM Knee System (DePuy Inc.), n = 10) or an established (PFCTM (DePuy Inc.), n = 11) knee system. All patients underwent computer navigation. Knee kinematics was assessed after implantation. Outcome measure was anterior-posterior translation between femur and tibia. We were able to demonstrate a significantly higher femoral rollback in the innovative implant group (p < 0.001). The mean rollback of the innovative system was 11.00 mm (95%-confidence interval [CI], 10.77-11.24), of the established system 8.12 mm (95%-CI, 7.84-8.42). This study revealed a significantly increased lateral as well as medial femoral rollback of knees with the innovative prosthesis design. Our intraoperative finding needs to be confirmed using fluoroscopic or radiographic three-dimensional matching under full-weight-bearing conditions after complete recovery from surgery.

Animal experimental investigation on the efficacy of antibiotic therapy with linezolid, vancomycin, cotrimoxazole, and rifampin in treatment of periprosthetic knee joint infections by MRSA.

AIMS: Periprosthetic joint infections (PJIs) are rare, but represent a great burden for the patient. In addition, the incidence of methicillin-resistant Staphylococcus aureus (MRSA) is increasing. The aim of this rat experiment was therefore to compare the antibiotics commonly used in the treatment of PJIs caused by MRSA. METHODS: For this purpose, sterilized steel implants were implanted into the femur of 77 rats. The metal devices were inoculated with suspensions of two different MRSA strains. The animals were divided into groups and treated with vancomycin, linezolid, cotrimoxazole, or rifampin as monotherapy, or with combination of antibiotics over a period of 14 days. After a two-day antibiotic-free interval, the implant was explanted, and bone, muscle, and periarticular tissue were microbiologically analyzed. RESULTS: Vancomycin and linezolid were able to significantly (p < 0.05) reduce the MRSA bacterial count at implants. No significant effect was found at the bone. Rifampin was the only monotherapy that significantly reduced the bacterial count on implant and bone. The combination with vancomycin or linezolid showed significant efficacy. Treatment with cotrimoxazole alone did not achieve a significant bacterial count reduction. The combination of linezolid plus rifampin was significantly more effective on implant and bone than the control group in both trials. CONCLUSION: Although rifampicin is effective as a monotherapy, it should not be used because of the high rate of resistance development. Our animal experiments showed the great importance of combination antibiotic therapies. In the future, investigations with higher case numbers, varied bacterial concentrations, and changes in individual drug dosages will be necessary to be able to draw an exact comparison, possibly within a clinical trial. Cite this article: Bone Joint Res 2022;11(3):143-151.

The antiapoptotic gene survivin is highly expressed in human chondrosarcoma and promotes drug resistance in chondrosarcoma cells in vitro.

BACKGROUND: Chondrosarcoma is virtually resistant to chemotherapy and radiation therapy. Survivin, the smallest member of the inhibitor of apoptosis protein family, is a critical factor for tumor progression and resistance to conventional therapeutic approaches in a wide range of malignancies. However, the role of survivin in chondrosarcoma has not been well studied. We examined the importance of survivin gene expression in chondrosarcoma and analysed its influences on proliferation, apoptosis and resistance to chemotherapy in vitro. METHODS: Resected chondrosarcoma specimens from which paraffin-embedded tissues could be extracted were available from 12 patients. In vitro experiments were performed in human chondrosarcoma cell lines SW1353 and Hs819.T. Immunohistochemistry, immunoblot, quantitative PCR, RNA interference, gene-overexpression and analyses of cell proliferation and apoptosis were performed. RESULTS: Expression of survivin protein was detected in all chondrosarcoma specimens analyzed, while undetectable in adult human cartilage. RNA interference targeting survivin resulted in a G2/M-arrest of the cell cycle and led to increased rates of apoptosis in chondrosarcoma cells in vitro. Overexpression of survivin resulted in pronounced resistance to doxorubicin treatment. CONCLUSIONS: These findings indicate that survivin plays a role in the pathogenesis and pronounced chemoresistance of high grade chondrosarcoma. Survivin antagonizing therapeutic strategies may lead to new treatment options in unresectable and metastasized chondrosarcoma.

The oncofetal gene survivin promotes cell proliferation and survival in primary human osteoblastic cells.

Survivin, the smallest member of the inhibitor of apoptosis gene family, is critical for the regulation of mitosis and maintenance of cell viability during embryonic development and cancer, while not being detectable in most adult differentiated tissues. We know little about whether survivin plays any physiological or pathophysiological role in the adult musculoskeletal system. We studied the expression of survivin in primary human osteoblastic cells and its biological functions in vitro. Survivin was detected by immunoblotting and real-time PCR. Subcellular localization was analyzed by immunofluorescence. Transfection of siRNA and plasmids coding for wild-type survivin was performed to study survivin function, i.e., proliferation and apoptosis assays. Survivin mRNA and protein are expressed in primary human osteoblastic cells. During interphase survivin localizes predominantly to the cytoplasmic compartment, which is relevant for the organization of the spindle apparatus during mitosis. Survivin knockdown resulted in an arrest of the cell cycle at the G(2)/M phase and increased rates of apoptosis. Elevated levels of survivin in primary human osteoblasts enhanced proliferation and cell viability. Taken together, we demonstrate for the first time that survivin is expressed in primary human osteoblastic cells on the mRNA and protein levels. Our results indicate that survivin is a critical factor for cell division and cell viability in primary human osteoblastic cells. Learning more about survivin's role in human osteoblasts could be an important step toward understanding the complex processes involved in bone homeostasis and remodeling.