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Computed tomography (CT) is a commonly used imaging modality in Emergency Departments (EDs), however its use is questionable in many low yield settings. The Emergency CT Head score (ECHS) is a recently published clinical tool that assists in stratifying the need for CT brain (CTB) for patients presenting without a history of trauma. We sought to validate this tool in an Australian ED setting.We prospectively evaluated 412 patients who received CTB without a history of trauma at a large Australian ED. We assessed them for the 4 main ECHS data points: focal neurological deficit on physical examination, new acute onset headache, transient neurological deficit, and a combination of new onset seizures with an altered conscious state. We examined their association with acute and chronic CTB findings. We then applied the ECHS to our data, calculating its sensitivity and its appropriateness at this single site via the calculation of a receiver operating curve (ROC).10.2% of all CTB performed were positive for an acute or chronic abnormality. Only sex (male) and focal motor deficit were independent predictors of positive CTB at univariate analysis. The ECHS did not perform as anticipated in our population, with a ROC area under the curve of 0.498. An ECHS score of0, which has been proposed as the threshold to not require imaging, had sensitivity of only 83.3% in our population.Further research and validation is required in order to safely implement the ECHS clinical score in the Australian ED setting.

Background A large number of CT brain (CTB) scans are ordered in the ED for older patients with a confirmed or possible head strike but no ongoing symptoms of a head injury. This study aimed to evaluate the effect of the Canadian CT head rule supplemented by the original published minimum inclusion criteria to assist clinician assessment of the need for CTB following minimal trauma fall in patients presenting from residential aged care facilities to a major metropolitan emergency department (ED). Methods This study was conducted as a pre- and post-intervention retrospective audit. The intervention involved implementation of a decision support tool to help clinicians assess patients presenting to the ED following a fall. The tool integrated the Canadian CT Head Rule (CCHR) in conjunction with a simplified set of inclusion criteria to help clinicians define a minimum threshold for a “minor head injury”. Outcome data pertaining to CT brain ordering practices and results were compared over symmetrical 3-month time periods pre- and post-intervention in 2 consecutive years. Results The study included 233 patients in the pre-intervention arm and 241 in the post-intervention arm. Baseline demographics and clinical characteristics were similar in both groups. There was a 20% reduction in the total number of CTB scans ordered following tool implementation, with 134 (57.0%) scans in the pre-intervention group and 90 (37.3%) in the post-intervention group (p p = 0.52). No variation was observed in medical management between groups, and no patients in either group underwent neurosurgical intervention. Conclusions Use of the CCHR supplemented by the original published minimum inclusion criteria appeared to safely reduce the number of CTB scans performed in residential aged care facility residents presenting to an ED after a fall, with no associated adverse outcomes. A larger study across multiple centres is required to determine widespread efficacy and safety of this tool.

Conventional therapies for patients with T-cell prolymphocytic leukemia (T-PLL), such as cytotoxic chemotherapy and alemtuzumab, have limited efficacy and considerable toxicity. Several novel agent classes have demonstrated preclinical activity in T-PLL, including inhibitors of the JAK/STAT and T-cell receptor pathways, as well as histone deacetylase (HDAC) inhibitors. Recently, the BCL-2 inhibitor venetoclax also showed some clinical activity in T-PLL. We sought to characterize functional apoptotic dependencies in T-PLL to identify a novel combination therapy in this disease. Twenty-four samples from patients with primary T-PLL were studied by using BH3 profiling, a functional assay to assess the propensity of a cell to undergo apoptosis (priming) and the relative dependence of a cell on different antiapoptotic proteins. Primary T-PLL cells had a relatively low level of priming for apoptosis and predominantly depended on BCL-2 and MCL-1 proteins for survival. Selective pharmacologic inhibition of BCL-2 or MCL-1 induced cell death in primary T-PLL cells. Targeting the JAK/STAT pathway with the JAK1/2 inhibitor ruxolitinib or HDAC with belinostat both independently increased dependence on BCL-2 but not MCL-1, thereby sensitizing T-PLL cells to venetoclax. Based on these results, we treated 2 patients with refractory T-PLL with a combination of venetoclax and ruxolitinib. We observed a deep response in JAK3-mutated T-PLL and a stabilization of the nonmutated disease. Our functional, precision-medicine–based approach identified inhibitors of HDAC and the JAK/STAT pathway as promising combination partners for venetoclax, warranting a clinical exploration of such combinations in T-PLL.