Performance of automated multiplex polymerase chain reaction (mPCR) using synovial fluid in the diagnosis of native joint septic arthritis in adults.

AIMS: This study aimed to assess the performance of an automated multiplex polymerase chain reaction (mPCR) technique for rapid diagnosis of native joint septic arthritis. PATIENTS AND METHODS: Consecutive patients with suspected septic arthritis undergoing aseptic diagnostic joint aspiration were included. The aspirate was used for analysis by mPCR and conventional microbiological analysis. A joint was classed as septic according to modified Newman criteria. Based on receiver operating characteristic (ROC) analysis, the area under the ROC curve (AUC) values of the mPCR and the synovial fluid culture were compared using the z-test. A total of 72 out of 76 consecutive patients (33 women, 39 men; mean age 64 years (22 to 92)) with suspected septic arthritis were included in this study. RESULTS: Of 72 patients, 42 (58%) were deemed to have septic joints. The sensitivity of mPCR and synovial fluid culture was 38% and 29%, respectively. No significant differences were found between the AUCs of both techniques (p = 0.138). A strong concordance of 89% (Cohen's kappa: 0.65) was shown. The mPCR failed to detect Staphylococcus aureus (n = 1) and Streptococcus pneumoniae (n = 1; no primer included in the mPCR), whereas the synovial fluid culture missed six microorganisms (positive mPCR: S. aureus (n = 2), Cutibacterium acnes (n = 3), coagulase-negative staphylococci (n = 2)). CONCLUSION: The automated mPCR showed at least a similar performance to the synovial fluid culture (the current benchmark) in diagnosing septic arthritis, having the great advantage of a shorter turnaround time (within five hours). Cite this article: Bone Joint J 2019;101-B:288-296.

The outcome of the surgical treatment of pelvic chondrosarcomas: a competing risk analysis of 58 tumours from a single centre.

AIMS: Few studies dealing with chondrosarcoma of the pelvis are currently available. Different data about the overall survival and prognostic factors have been published but without a detailed analysis of surgery-related complications. We aimed to analyse the outcome of a series of pelvic chondrosarcomas treated at a single institution, with particular attention to the prognostic factors. Based on a competing risk model, our objective was to identify risk factors for the development of complications. PATIENTS AND METHODS: In a retrospective single-centre study, 58 chondrosarcomas (26 patients alive, 32 patients dead) of the pelvis were reviewed. The mean follow-up was 13 years (one week to 23.1 years). RESULTS: A total of 26 patients (45%) were alive and 32 patients (55%) had died. Overall survival was 76%, 55% and 45% at one, five and ten years post-operatively, respectively. In a competing risk model the cumulative risk of the development of a surgery-related complication was 64% at six months and 69% at one year, post-operatively, respectively. Endoprosthetic reconstruction was a significant risk factor for the development of complications (p = 0.006). Complications were not significantly related to age or the location or grade of the tumour (p = 0.823, p = 0.976, p = 0.858). The development of complications did not have a negative effect on survival (p = 0.147). CONCLUSION: This is the first study with competing risk analysis of surgery-related complications in patients with a pelvic chondrosarcoma. The surgery in these patients remains prone to complications. Endoprosthetic reconstruction significantly increases the risk of the development of complications (p = 0.006). A competing risk model showed that the development of complications does not have a negative influence on overall survival (p = 0.147). An aggressive, surgical resection with the goal of achieving wide margins whenever possible remains the mainstay of treatment. Cite this article: Bone Joint J 2017;99-B:686-96.

Survival, failure modes and function of combined distal femur and proximal tibia reconstruction following tumor resection.

BACKGROUND: Tumor spread to the knee joint or skip metastasis to the adjacent bones of the knee require reconstruction with combined distal femur and proximal tibia replacements. The literature on implant survival and failure modes with this type of reconstruction is sparse. The goals of this study were to determine the implant survival, the different failure modes and the functional outcome of this megaendoprosthetic reconstruction. PATIENTS AND METHODS: Thirty-nine patients with combined distal femur and proximal tibia reconstruction were retrospectively reviewed. Median follow-up was 8.8 years (quartiles 4.7-15.5 years). Twenty-one patients received combined distal femur and proximal tibia reconstruction as a primary mode of reconstruction, 18 patients as revision surgery after failed tumor prosthesis. For survival estimations, competing risk analyses were performed. RESULTS: The revision-free survival at five years was 42% (95% CI 22%-56%) and implant survival with exchange of the original implant was 54% (95% CI 35%-68%). Five-year revision-free survival for soft tissue failure was 72% (95% CI 52%-84%), for infection 67% (95% CI 48%-80%), for structural failure 82% (95% CI 63%-91%), for aseptic loosening and tumor progression 97% (95% CI 82%-99%), respectively. Patients with revision surgery had higher risk for infection (p < 0.001), structural failure (p = 0.037) and shorter revision-free- (p = 0.025) and implant-survival (p = 0.006). Limb survival at 20 years was 94%. Mean musculoskeletal Tumor Society score was 76%. CONCLUSION: Despite high failure rates with short revision-free survivals, combined distal femur and proximal tibia reconstruction achieved longtime limb survival in the majority of patients with satisfying function.

Extendible Prostheses for Children After Resection of Primary Malignant Bone Tumor: Twenty-seven Years of Experience.

BACKGROUND: Endoprosthetic replacement in children following resection of a malignant bone tumor still is controversial because of the high number of reoperations. The aim of this study was to evaluate the long-term outcome with respect to limb-lengthening potential, satisfaction rate, and complications after implantation of extendible devices. METHODS: Seventy-one patients with a sarcoma in an extremity who had been followed for more than twenty-four months (mean, 131.6 months; range, 27.2 to 281.8 months) after tumor resection and prosthetic reconstruction with an extendible device were analyzed. The mean age at the time of the operation was ten years (range, four to sixteen years). The complication-free survival rate was evaluated with competing-risk analysis. Clinical outcomes and complications were rated with use of the Musculoskeletal Tumor Society (MSTS) score and a failure mode classification for segmental tumor endoprostheses, respectively. RESULTS: Twelve of seventy-one patients died of their disease. The overall MSTS score averaged 87.8% (range, 23.3% to 100%). The most common mode of failure was soft-tissue failure (46%), followed by structural failure (28%), infection (17%), and aseptic loosening (8%); only 2% of the children had local recurrence. An average of 4.4 lengthening operations per patient were required for an average limb elongation of 70.8 mm (range, 0 to 224 mm). An average of 2.5 operations (range, zero to eleven) per patient were performed for complications. CONCLUSIONS: Although limb lengthening with an extendible endoprosthesis seems to be effective, many children have related complications. These data will be a source of preoperative information for children and parents, and will provide a benchmark for further clinical improvements.

Anticancer effects of zoledronic acid against human osteosarcoma cells.

Based on neoadjuvant chemotherapy, the prognosis of osteosarcoma patients has improved dramatically. However, due to therapy resistance in patient subgroups, the development of new treatment strategies is still of utmost importance. The aim of our study was to test the effects of the nitrogen-containing bisphosphonate zoledronic acid (ZOL) on osteosarcoma cell lines (N = 9). Exposure to ZOL at low micromolar concentrations induced a dose- and time-dependent block of DNA synthesis and cell cycle progression followed by microfilament breakdown and apoptosis induction. The ZOL-induced cell cycle accumulation in S phase was accompanied by significant changes in the expression of cyclins and cyclin-dependent kinase inhibitors with a prominent loss of cyclin E and D1. ZOL not only inhibited growth but also migration of osteosarcoma cells. The mevalonate pathway intermediary geranyl-geraniol (GGOH) but not farnesol (FOH) significantly inhibited the anticancer effects of ZOL against osteosarcoma cells. Correspondingly, ZOL sensitivity correlated with the blockade of protein geranylgeranylation indicated by unprenylated Rap1. Overexpression of even high levels of P-glycoprotein, as frequently present in therapy-resistant osteosarcomas, did not impair the anticancer activity of ZOL. Summarizing, our data suggest that ZOL, which selectively accumulates in the bone, represents a promising agent to improve osteosarcoma therapy.

Intrinsic and acquired forms of resistance against the anticancer ruthenium compound KP1019 [indazolium trans-[tetrachlorobis(1H-indazole)ruthenate (III)] (FFC14A).

KP1019 [indazolium trans-[tetrachlorobis(1H-indazole)ruthenate (III)] (FFC14A) is a metal complex with promising anticancer activity. Since chemoresistance is a major obstacle in chemotherapy, this study investigated the influence of several drug resistance mechanisms on the anticancer activity of KP1019. Here we demonstrate that the cytotoxic effects of KP1019 are neither substantially hampered by overexpression of the drug resistance proteins multidrug resistance-related protein 1, breast cancer resistance protein, and lung resistance protein nor the transferrin receptor and only marginally by the cellular p53 status. In contrast, P-glycoprotein overexpression weakly but significantly (up to 2-fold) reduced KP1019 activity. P-glycoprotein-related resistance was based on reduced intracellular KP1019 accumulation and reversible by known P-glycoprotein modulators. KP1019 dose dependently inhibited ATPase activity of P-glycoprotein with a K(i) of approximately 31 microM. Furthermore, it potently blocked P-glycoprotein-mediated rhodamine 123 efflux under serum-free conditions (EC(50), approximately 8 microM), however, with reduced activity at increased serum concentrations (EC(50) at 10% serum, approximately 35 microM). Moreover, P-glycoprotein-mediated daunomycin resistance could only be marginally restored by KP1019 in serum-containing medium, also indicating an influence of serum proteins on the interaction between KP1019 and P-glycoprotein. Acquired KP1019 resistance was investigated by selecting KB-3-1 cells against KP1019 for more than 1 year. Only an approximately 2-fold KP1019 resistance could be induced, which unexpectedly was not due to overexpression of P-glycoprotein or other efflux pumps. Accordingly, KP1019-resistant cells did not display reduced drug accumulation. Their unique cross-resistance pattern confirmed an ABC transporter-independent resistance phenotype. In summary, the likeliness of acquiring insensitivity to KP1019 during therapy is expected to be low, and resistance should not be based on overexpression of drug efflux transporters.