The Effectiveness of Prophylactic Ankle Braces in Reducing the Incidence of Acute Ankle Injuries in Adolescent Athletes: A Critically Appraised Topic

Clinical Scenario: Ankle injuries constitute a large number of injuries sustained by adolescent athletes participating in high school athletics. Prophylactic ankle bracing may be an effective and efficient method to reduce the incidence of ankle injuries in adolescent athletes in the secondary-school setting. Clinical Question: Do prophylactic ankle braces reduce the incidence of acute ankle injuries in adolescent athletes? Summary of Key Findings: Two of the three included studies reported that prophylactic ankle braces reduced the incidence of ankle injuries compared with no ankle bracing. Clinical Bottom Line: There is moderate evidence to support the use of prophylactic ankle braces in adolescent athletes, particularly those who participate in football and basketball, to reduce the incidence of acute ankle injuries. Strength of Recommendation: Grade B evidence exists that prophylactic ankle braces reduce the incidence of acute ankle injuries in adolescent athletes

Inhibition of Pol I transcription treats murine and human AML by targeting the leukemia-initiating cell population

Despite the development of novel drugs, the prospects for many patients with acute myeloid leukemia (AML) remain dismal. This study reveals that the selective inhibitor of RNA polymerase I (Pol I) transcription, CX-5461, effectively treats aggressive AML, including mixed-lineage leukemia-driven AML, and outperforms standard chemotherapies. In addition to the previously characterized mechanism of action of CX-5461 (ie, the induction of p53-dependent apoptotic cell death), the inhibition of Pol I transcription also demonstrates potent efficacy in p53null AML in vivo. This significant survival advantage in both p53WT and p53null leukemic mice treated with CX-5461 is associated with activation of the checkpoint kinases 1/2, an aberrant G2/M cell-cycle progression and induction of myeloid differentiation of the leukemic blasts. The ability to target the leukemic-initiating cell population is thought to be essential for lasting therapeutic benefit. Most strikingly, the acute inhibition of Pol I transcription reduces both the leukemic granulocyte-macrophage progenitor and leukemia-initiating cell (LIC) populations, and suppresses their clonogenic capacity. This suggests that dysregulated Pol I transcription is essential for the maintenance of their leukemia-initiating potential. Together, these findings demonstrate the therapeutic utility of thisnewclass of inhibitors to treat highly aggressive AML by targeting LICs