Assessing reproducibility for radiographic measurement of leg length inequality after total hip replacement

Leg length inequality (LLI) as a result of total hip replacement can cause considerable morbidity. Although LLI was described when the technique was popularised in the 1960s, it remains a significant challenge to arthroplasty surgeons. This study reviews the established practice for the measurement of LLI on plain antero-posterior radiograph, and compares these techniques to two methods used locally. The radiographs of 35 patients were measured using four techniques. All four methods yielded an interclass correlation co-efficient of ≥0.90 for inter reader reliability. This study shows that the four methods are comparable for reliability, while a composite method, measuring from the centre of femoral rotation to the inferior teardrop and then to the lesser trochanter, has the added advantage of providing extra information on component position as well as an overall measure of LLI

Small Interfering RNA Targeted to IGF-IR Delays Tumor Growth and Induces Proinflammatory Cytokines in a Mouse Breast Cancer Model

Insulin-like growth factor I (IGF-I) and its type I receptor (IGF-IR) play significant roles in tumorigenesis and in immune response. Here, we wanted to know whether an RNA interference approach targeted to IGF-IR could be used for specific antitumor immunostimulation in a breast cancer model. For that, we evaluated short interfering RNA (siRNAs) for inhibition of in vivo tumor growth and immunological stimulation in immunocompetent mice. We designed 2′-O-methyl-modified siRNAs to inhibit expression of IGF-IR in two murine breast cancer cell lines (EMT6, C4HD). Cell transfection of IGF-IR siRNAs decreased proliferation, diminished phosphorylation of downstream signaling pathway proteins, AKT and ERK, and caused a G0/G1 cell cycle block. The IGF-IR silencing also induced secretion of two proinflammatory cytokines, TNF- α and IFN-γ. When we transfected C4HD cells with siRNAs targeting IGF-IR, mammary tumor growth was strongly delayed in syngenic mice. Histology of developing tumors in mice grafted with IGF-IR siRNA treated C4HD cells revealed a low mitotic index, and infiltration of lymphocytes and polymorphonuclear neutrophils, suggesting activation of an antitumor immune response. When we used C4HD cells treated with siRNA as an immunogen, we observed an increase in delayed-type hypersensitivity and the presence of cytotoxic splenocytes against wild-type C4HD cells, indicative of evolving immune response. Our findings show that silencing IGF-IR using synthetic siRNA bearing 2′-O-methyl nucleotides may offer a new clinical approach for treatment of mammary tumors expressing IGF-IR. Interestingly, our work also suggests that crosstalk between IGF-I axis and antitumor immune response can mobilize proinflammatory cytokines

A review of symptomatic leg length inequality following total hip arthroplasty

Leg length inequality (LLI) following total hip replacement is a complication which features increasingly in the recent literature. The definition of LLI is complicated by lack of consensus regarding radiological measurement, clinical measurement and the incomplete relationship between LLI and associated symptoms. This paper reviews 79 reports relating to LLI post hip replacement, detailing definitions and classification and highlighting patient populations prone to symptomatic LLI. While there is no universal definition of LLI, there is a broad consensus that less than 10 mm of difference on AP view plain radiographs is clinically acceptable. There are few techniques described that consistently produce a postoperative LLI of less than this magnitude. Where postoperative LLI exists, lengthening appears to cause more problems than shortening. In cases of mild LLI, non-surgical management produces adequate outcomes in the majority of cases, with functional LLI cases doing better than those with true LLI. Operative correction is effective in half of cases, even where nerve palsy is present, and remains an important option of last resort. Poor outcomes in patients with LLI may be minimised if individuals at risk are identified and counselled appropriately