To compare pre-referral microbiology and previous bone excision in long bone osteomyelitis with intra-operative microbiology from a specialist centre. A prospective observational cohort study of patients referred to a single tertiary centre who met the following criteria: (i) aged ≥18 years, (ii) received surgery for long bone osteomyelitis and (iii) met diagnostic criteria for long bone osteomyelitis. Patient demographics, referral microbiology and previous surgical history were collected at the time of initial clinic appointment. During surgery, a minimum of 5 intra-operative deep tissue samples were sent for microbiology. Antimicrobial options were classified from the results of susceptibility testing using the BACH classification of long bone osteomyelitis as either Ax (unknown or culture negative), A1 (good options available) or A2 (limited options available). The cultures and susceptibility of pre-referral microbiology were compared to the new intra-operative sampling results. In addition, an association between previous osteomyelitis excision and antimicrobial options were investigated.Aim
Method
With modern polychemotherapy Ewing’s sarcoma exhibit remarkable chemosensitivity leading to 5-year survival rates approaching 60–70%. However, in the last decade, no significant progress has been achieved in terms of improved cure rates and quality of life. In addition, prognosis is poor either in relapsed patients and in patients with metastasis at diagnosis. Thus, it is imperative to develop novel therapeutic strategies and to identify markers for risk-adapted therapies. The PROTHETS European Consortium through collaborative studies defined prognostic markers and new therapeutic targets in the Ewing’s sarcoma family of tumours (ESFT), to provide rigorous scientific justifications for the development of clinical trials for this rare disease. Genetic studies have been performed for the screening of high-risk patients and patients responding differently to chemotherapy. Between others, these studies identified in gluthation metabolism a major pathway regulating Ewing’s sarcoma chemoresistance. The prognostic relevance of glutathione metabolism pathway was validated by RT-PCR and the expression of MGST1, the microsomal glutathione transferase (GST), was found to clearly predict EWS prognosis. MGST1 expression was associated with doxorubicin chemo sensitivity. This prompted to assess the in vitro effectiveness a new anticancer agent (NBDHEX) that efficiently inhibits GST enzymes.. The consortium have collected more than 600 cases in specific tissue arrays for validation studies. Their use allowed the identification of some markers of prognosis, either conventional or new (ki-67, adhesion proteins, GAL3BP). Overall, theses studies started to define possible forthcoming risk-adapted strategies. Another goal of the project was the creation of new tools and drugs as well as the optimization of molecular approaches against three therapeutic targets, EWS-FLI1, CD99 and IGF-IR that have great potential in terms of clinical application. The studies on IGF-IR have provide the rationale for the currently on-going clinical studies in Ewing’s sarcoma.
