Symptomatic leg length discrepancy after total hip arthroplasty is associated with new onset of lower back pain.

BACKGROUND: Leg length discrepancy (LLD) is common after total hip arthroplasty (THA) with a plethora of clinical consequences. The associations between symptomatic (sLLD; disturbing perception of anatomical leg length discrepancy), anatomical (aLLD; side difference in leg length between the center of rotation of the hip and the center of the ankle joint) and intraarticular (iLLD; side difference between the tear drop figure and the most prominent point of the trochanter minor) LLD and lower back have not yet been reported in the literature. We performed a retrospective study to answer if postoperative (1) symptomatic LLD, (2) anatomic LLD, and (3) a change in intraarticular leg length are associated with lower back pain in patients undergoing THA. Further, we aimed to answer (4) whether symptomatic LLD is associated with the magnitude of anatomical LLD and the change in intraarticular leg length. HYPOTHESIS: LLD after THA is associated with lower back pain. MATERIALS AND METHODS: Seventy-nine consecutive patients were retrospectively analyzed for the presence of aLLD and iLLD using EOS™ and X-rays, and were interviewed for the presence of sLLD and lower back pain using a questionnaire 5 years after primary THA. RESULTS: Postoperative new onset of lower back pain was reported by 9 (11%) patients. Twenty (25%) patients reported sLLD. Anatomical LLD>5mm was present in 44 (56%) (median 8.0 (IQR -3.0 to 12.0; range -22 to 22) mm) and>10mm in 17 (22%) (median 12.0 (IQR 11.0 to 16.5; range -22 to 22) mm) patients. iLLD changed>5mm in 44 (56%) (median 8.5 (IQR 7.0 to 10.0; range -8 to 18) mm) and>10mm in 10 (13%) (median 14.0 (IQR 12.5 to 14.5; range 11 to 18) mm). New onset lower back pain was associated with sLLD (p=0.002) but not with aLLD or iLLD. Patients without preoperative lower back pain had a statistically significant association between presence of sLLD and an aLLD of >10mm (p=0.01). CONCLUSIONS: Symptomatic LLD after primary THA is associated with postoperative new onset of lower back pain irrespective of the magnitude of LLD. In patients without lower back pain prior to THA, symptomatic LLD is associated with anatomical LLD of more than 10mm. LEVEL OF EVIDENCE: IV.

Total hip arthroplasty with accolade/trident through the direct minimally invasive anterior approach without traction table: Learning curve and results after a minimum of 5 years.

BACKGROUND: The direct minimally invasive anterior approach (DMIAA) in total hip arthroplasty (THA) is widely accepted. In our department the DMIAA according to Rachbauer together with the Trident cup and Accolade stem was introduced in 2004. The purpose of the study was to demonstrate the five-year results and to analyze the learning curve of a new introduced approach. PATIENTS AND METHODS: Between July 2004 and May 2006, a consecutive series of 151 THA in 147 patients was retrospectively analyzed. All patients were planned to received a THA with the Accolade/Trident implant system using the DMIAA without traction table. Clinical and radiographic data, complications and survivorship were documented with a follow-up of at least 5 years. RESULTS: Regarding cup implantation, there were 11 (7.3%) failed intentions to treat due to missing pressfit (8 cases) and acetabular floor perforation (3 cases). No failed intentions to treat occurred during stem implantation. Total implant survival after 5 years follow-up after exclusion of 11 cases with failed intention to treat (N=140) was 96.9% (SD 1.4; CI 94.3-99.6). After exclusion of the failed intentions to treat (N=140, N=4 in the first 20 cases), there was significant (p<0.001) difference between the first 16 implants with a 5 year-survival of 83.2% (SD 8.6; CI 66.4-100) and 95.7% (SD 0.9; CI 93.9-97.5) for the following 124 implants. Radiolucent lines were observed in Gruen zone 1 in 3.3% and in Gruen zone 1 and 2 in 1.1%. DISCUSSION: THA with Accolade/Trident using the DMIAA without traction table according to Rachbauer temporary exposed patients to a higher risk of implant revisions, which was normalized after the first 20 cases. Results of the learning curve are comparable to other techniques using an orthopaedic traction table. After the typical learning curve, the rate of 5 years implant failure is in accordance with the registry data for non-cemented implants. The Accolade stem showed minimal radiographic signs of radiolucency. LEVEL OF EVIDENCE: IV, retrospective, consecutive case series.

Evaluation of quercetin as a potential drug in osteosarcoma treatment.

BACKGROUND: Osteosarcoma is the most common malignant bone tumor in children and young adults. Since the introduction of chemotherapy, the 5-year survival rate of patients with non-metastatic osteosarcoma is ~70%. The main problems in osteosarcoma therapy are the occurrence of metastases, severe side-effects and chemoresistance. Antiproliferative and apoptotic effects of quercetin were shown in several types of cancers, including breast cancer and lung carcinoma. MATERIALS AND METHODS: The present study investigates the cytotoxic potential of quercetin, a dietary flavonoid, in a highly metastasizing human osteosarcoma cell line, 143B. RESULTS: We found that quercetin induces growth inhibition, G2/M phase arrest, and apoptosis in the 143B osteosarcoma cell line. We also observed impaired adhesion and migratory potential after the addition of quercetin. CONCLUSION: Since quercetin has already been shown to have low side effects in a clinical phase I trial in advanced cancer patients, this compound may have considerable potential for osteosarcoma treatment.

A new method for repeated drug infusion into the femoral artery of mice.

Intraarterial chemotherapy (IAC) is considered effective for the treatment of solid tumors with high local doses of systemically toxic chemotherapeutics. Osteosarcoma, which is often located in the extremities, is a potential target for IAC. However, the efficacy of this treatment modality has varied, and standardized protocols are difficult to establish due to tumor heterogeneity and the limited numbers of patients available for clinical trials. Reproducible experimental models are needed to further investigate IAC in osteosarcoma. Here, we describe a new microsurgical technique for repeated infusion of drugs into the mouse femoral artery for local treatment of experimental intratibial metastasizing osteosarcoma. We successfully achieved 5 catheterizations at 3-d intervals in 70% of the mice tested. Laser speckle imaging indicated a maximal 50% reduction in blood flow around the ankle region of catheterized legs infused with 0.5 mg/kg cisplatin. However, blood flow in the front feet was affected only minimally. Histologic examination of catheterized arteries of saline control or cisplatin-treated mice showed circular fibrinoid media necrosis and partial thrombosis, but total occlusion of the arteries was not observed. The method we describe for repeated transient catheterization of the mouse femoral artery likely will be useful in future studies comparing the efficacies of intraarterial and systemic cisplatin treatment of intratibial metastasizing osteosarcoma in mice under standardized conditions.

Macrophage migration inhibitory factor does not modulate co-activation of androgen receptor by Jab1/CSN5.

Macrophage migration inhibitory factor (MIF) is a pro-inflammatory immune modulator that plays an important role in the regulation of innate and adaptive immune responses. MIF signaling involves CD74/CD44 membrane receptor complexes, the chemokine receptors CXCR2 and 4 as well as uptake by non-receptor mediated endocytosis. Endocytosed or endogenous MIF interacts with Jun activation domain-binding protein 1 (Jab1), originally described as transcriptional co-activator for the transcription factor AP-1, that is also known as subunit 5 of the COP9 signalosome (CSN5). Since Jab1/CSN5 also functions as a co-activator for a number of steroid hormone receptors (SHRs), it had been speculated that MIF could modulate Jab1/CSN5-SHR interactions. Here we show (i) that fluorescently labeled MIF is internalized by NIH 3T3 cells within minutes, (ii) compromises the induction of phospho-c-Jun levels by TNFalpha and PMA and, hence, is biologically active, but (iii) is not able to interfere with co-activation by Jab1/CSN5 of the androgen receptor.