Standardised virtual fracture clinic management of Achilles tendon ruptures is safe and reproducible

BackgroundTraditional fracture clinics are some of the busiest clinics in a hospital, often with significant patient waiting times and delays. The use of virtual fracture clinic (VFC) for the management of certain injuries to reduce the workload on the traditional fracture clinic, in addition to reducing costs is growing in popularity. The tendoachilles is the most frequently ruptured tendon in the body but despite this, management remains a keenly debated topic.MethodsAll adult patients referred to the VFC with an actual or suspected Achilles tendon rupture were identified between January 2015 to October 2017.ResultsThis study found that patient with and acute achilles tendon ruptures managed according to a standardised VFC protocol had a re-rupture rate of 3.82%.ConclusionsOne of the advantages of a VFC model that is standardised, initiated in the ED, is that it has no variation in outcome seen in our patient group.     

A synthetic peptide targeting the BH4 domain of Bcl-2 induces apoptosis in multiple myeloma and follicular lymphoma cells alone or in combination with agents targeting the BH3-binding pocket of Bcl-2

Bcl-2 inhibits apoptosis by two distinct mechanisms but only one is targeted to treat Bcl-2-positive malignancies. In this mechanism, the BH1-3 domains of Bcl-2 form a hydrophobic pocket, binding and inhibiting pro-apoptotic proteins, including Bim. In the other mechanism, the BH4 domain mediates interaction of Bcl-2 with inositol 1,4, 5-trisphosphate receptors (IP₃Rs), inhibiting pro-apoptotic Ca²⁺ signals. The current anti-Bcl-2 agents, ABT-263 (Navitoclax) and ABT-199 (Venetoclax), induce apoptosis by displacing pro-apoptotic proteins from the hydrophobic pocket, but do not inhibit Bcl-2-IP₃R interaction. Therefore, to target this interaction we developed BIRD-2 (Bcl-2 IP₃ Receptor Disruptor-2), a decoy peptide that binds to the BH4 domain, blocking Bcl-2-IP₃R interaction and thus inducing Ca²⁺-mediated apoptosis in chronic lymphocytic leukemia, multiple myeloma, and follicular lymphoma cells, including cells resistant to ABT-263, ABT-199, or the Bruton’s tyrosine kinase inhibitor Ibrutinib. Moreover, combining BIRD-2 with ABT-263 or ABT-199 enhances apoptosis induction compared to single agent treatment. Overall, these findings provide strong rationale for developing novel therapeutic agents that mimic the action of BIRD-2 in targeting the BH4 domain of Bcl-2 and disrupting Bcl-2-IP₃R interaction.     

Reduced or painful jaw movement after collision-related injuries: a population-based study

BACKGROUND: The authors report the incidence of and factors associated with reduced and/or painful jaw movement after motor vehicle collisions that resulted in whiplash-associated disorders (WADs). METHODS: All adults filing collision-related personal injury claims during an 18-month period in Saskatchewan, Canada, were evaluated via questionnaire to determine demographic characteristics, precollision health (including jaw pain), collision parameters and collision-related symptoms, including reduced and/or painful jaw movement and injury-related neck pain. The authors excluded patients who were hospitalized for more than two days and those who sustained injuries as a pedestrian, bicyclist or motorcyclist. In determining incidence rates, the authors also excluded those who had had jaw pain before the collision. RESULTS: The incidence of reduced and/or painful jaw movement was 14.9 percent (n = 1,158), and it was higher in subjects with WADs (15.8 percent) than in those without WADs (4.7 percent; relative risk = 3.36, 95 percent confidence interval, 2.36 to 4.78). Within the WAD injuries, multivariable logistic regression revealed that the onset of reduced and/or painful jaw movement was associated with female sex; age < 50 years; having hit one's head in the collision; and postinjury symptoms of difficulty swallowing, ringing in the ears, dizziness or unsteadiness, and more intense neck pain. Collision parameters, such as head position at the time of the crash and headrest use and type, were not associated with onset of jaw symptoms. CONCLUSIONS: Reduced or painful jaw movement was more common in people with WADs than in those with other collision-related injuries. Among those with WADs, reduced or painful jaw movement was more common in women and younger people. CLINICAL IMPLICATIONS: Reduced or painful jaw movement is an important aspect of WADs, and more studies are needed to determine how to best assess and treat this problem.