Blocking “don't eat me” signal of CD47-SIRPα in hematological malignancies,an in-depth review

Hematological malignancies express high levels of CD47 as a mechanism of immune evasion. CD47-SIRPα triggers a cascade of events that inhibit phagocytosis. Preclinical research supports several models of antibody-mediated blockade of CD47-SIRPα resulting in cell death signaling, phagocytosis of cells bearing stress signals, and priming of tumor-specific T cell responses. Four different antibody molecules designed to target the CD47-SIRPα interaction in malignancy are currently being studied in clinical trials: Hu5F9-G4, CC-90002, TTI-621, and ALX-148. Hu5F9-G4, a humanized anti-CD47 blocking antibody is currently being studied in four different Phase I trials. These studies may lay the groundwork for therapeutic bispecific antibodies. Bispecific antibody (CD20-CD47SL) fusion of anti-CD20 (Rituximab) and anti-CD47 also demonstrated a synergistic effect against lymphoma in preclinical models. This review summarizes the large body of preclinical evidence and emerging clinical data supporting the use of antibodies designed to target the CD47-SIRPα interaction in leukemia, lymphoma and multiple myeloma.     

Acetabular fractures,anatomy and implications for treatment

Acetabular fractures are relatively uncommon and their definitive treatment tends to be focused on specialist major trauma centres. This can make both accurate diagnosis and management challenging, particularly in hospitals where they are rarely seen. Contemporary management of these injuries owes a lot to the work of Judet and Letournel undertaken in the 1970s. The key to understanding these injuries is to know the embryology and development of the pelvis and then be able to appreciate its three-dimensional structure from two-dimensional X-rays. This can then be overlaid with the Judet classification and the action of force vectors encountered in various mechanisms of injury. It is also important to realise the ageing demographics of this group of patients and the complexities this adds to classification and ultimately treatment. Finally, the presence of an acetabular fracture is often seen in association with a number of other injuries. It is imperative that these are appropriately and contemporaneously diagnosed so that a comprehensive management plan may be instituted to give the best outcomes. However, even with optimal management the prognosis is guarded with a majority of patients suffering some degree of functional loss and this must be made clear to the patient from the outset.