Ben Batalla, I. et al. (2017) Axl blockade by BGB324 inhibits BCR-ABL tyrosine kinase inhibitor-sensitive and -resistant chronic myeloid leukemia. Clinical Cancer Research, 23(9), pp. 2289-2300. (doi:10.1158/1078-0432.CCR-16-1930 This is the author's final accepted version.There may be differences between this version and the published version. You are advised to consult the publisher's version if you wish to cite from it.http://eprints.gla.ac.uk/131767/ STATEMENT OF TRANSLATIONAL RELEVANCEABL tyrosine kinase inhibitors (TKI) are employed for chronic myeloid leukemia (CML) treatment and induce durable remissions in the majority of patients. However, resistant disease and persistence of BCR-ABL1-independent leukemia stem and progenitor cells remain clinical challenges.Furthermore, ABL-TKI are associated with the risk of severe side effects in long term use. Therefore, novel therapeutic strategies are warranted to target persisting stem cells and resistant clones alone or in combination with ABL-TKI.We demonstrate here the activity of an Axl inhibitor, BGB324, against TKI-sensitive and -resistant BCR-ABL1 positive cells, including T315I-mutated and ponatinib-resistant primary cells. Inhibition of Axl with BGB324 exerted therapeutic effects in complementary T315I-mutated and ponatinib-resistant preclinical mouse models. BGB324 was well-tolerated in Phase 1 clinical trials in healthy volunteers and AML patients (BGBC001, BGBC003 ongoing). Thus our findings can be rapidly translated to the clinics and BGB324 holds promise to improve treatment of CML patients.

Meckel diverticulum, the commonest congenital abnormality of the gastrointestinal tract, may be difficult to diagnose. Appearances on CT are often non-specific unless there is connection to the umbilicus or a complication has occurred. We report a case of an inflamed Meckel diverticulum seen on CT.

Current guidelines support the well-established clinical practice that patients who present with atrial fi brillation (AF) of less than 48 hours duration should be considered for cardioversion, even in the absence of pre-existing anticoagulation. However, with increasing evidence that short runs of AF confer signifi cant risk of stroke, on what evidence is this 48-hour rule based and is it time to adopt a new approach? We review existing evidence and suggest a novel approach to risk stratifi cation in this setting. Overall, the risk of thromboembolism associated with acute cardioversion of patients with AF that is estimated to be of <48 hours duration is low. However, this risk varies widely depending on patient characteristics. From existing evidence, we show that using the CHA 2 DS 2 -VASc score may allow better selection of appropriate patients in order to prevent exposing specifi c patient groups to an unacceptably high risk of a potentially devastating complication. KEYWORDS : Anticoagulants , atrial fi brillation , cardioversion , electrical cardioversion , stroke , thromboembolism IntroductionInternational guidelines support the well-established clinical practice that patients who present with non-valvular atrial fibrillation (AF) of less than 48 hours duration should be considered for cardioversion, even in the absence of pre-existing anticoagulation.1,2 The risk with more prolonged periods of AF is that restoration of sinus rhythm may precipitate embolism of intra-atrial thrombus causing stroke. However, with increasing evidence that even short runs of AF confer significant risk of stroke, [3][4][5][6] this review examines the evidence supporting the '48-hour rule' and suggests a novel approach to risk stratification in this setting. Search strategy and selection criteriaData for this review were identified by searches of PubMed using combinations of the terms 'atrial fibrillation', 'cardioversion' and 'thromboembolism'. References sourced ABSTRACTCardioverting acute atrial fi brillation and the risk of thromboembolism: not all patients are created equal from relevant articles were also included. Additional references were identified from review of current international guidelines on the management of atrial fibrillation.

In this population-based study, adherence to laboratory monitoring guidelines was suboptimal. There was a positive correlation with total amiodarone exposure and biochemical abnormalities and development of thyroid disease compared to the general population, highlighting the need for improvement and continued amiodarone monitoring.

Aim Cerebrospinal fluid (CSF) analysis for xanthochromia is routinely used to exclude subarachnoid haemorrhage (SAH). In this study, we evaluated the sensitivity and specificity of xanthochromia (by NEQAS-spectrophotometry) in routine clinical practice in three acute hospitals, in patients with suspected SAH. We explored whether including CSF red cell count (RCC) with xanthochromia improved diagnostic accuracy. Methods In this retrospective analysis, all xanthochromia results were assessed over three consecutive years. Clinical information and Registry data were analysed to find all patients diagnosed with SAH. We correlated xanthochromia data with clinical and radiological findings. Results There were 1761 xanthochromia performed. Of these, 26 (1.5%) were positive, 1624 (92%) negative and 72 (4.1%) were inconclusive. Of the 26 tests that were positive, 9 (35%) had confirmed SAH, 17 (65%) were falsely positive, with no false negative tests in our series. Xanthochromia identified 6% of all SAH diagnosed in the study. Incorporating RCC <1000 with xanthochromia, reducing false positive tests by 38% and inconclusive test by 85%. Conclusion The positive yield of xanthochromia is low but identified 6% of SAH. NEQAS-spectrophotometry is an excellent diagnostic method with 100% sensitivity, 99% specificity. Incorporating RCC markedly reduces false positive and inconclusive tests reducing need for further imaging.