Prevalence of left ventricular hypertrabeculation/noncompaction among children with sickle cell disease.

OBJECTIVES: Incidence of sickle cell disease (SCD) in Ireland has dramatically increased. Disease survival has also steadily improved however cardiovascular manifestations remain important causes of morbidity. These include reports of left ventricular hypertrabeculation (LVHT)/noncompaction. We sought to investigate the prevalence of LVHT among a large cohort of children with SCD. METHODS: We retrospectively reviewed the records of all patients with a diagnosis of SCD who had undergone surveillance echocardiography at Our Lady's Children's Hospital Crumlin (OLCHC) from 1998 to 2015. Demographics, hemoglobin phenotype and treatment information was recorded. LV systolic function, evidence of LVHT, and possible pulmonary arterial hypertension was assessed. RESULTS: Two hundred thirty-six patients had echocardiograms available for interpretation. One hundred twenty-one (51.3%) were female; mean age was 11.3 years (± 4.1 years). Twenty-six patients (11%) had features of LVHT on echocardiography. Eleven patients (4.7%) had borderline features of LVHT. Mean LVEDD across the whole cohort was 4.2 ± 0.69 cm, LVEDD z-score of 1.44 ± 1.9, and mean LVSF was 37.3% ±15.7%. There were no significant differences in terms of age, LVEDD, LVEDD z-score, or LVSF between patients with and those without LVHT. CONCLUSIONS: The prevalence of LVHT/noncompaction in children with SCD is lower than the adult population and LV systolic function is well preserved throughout our patient group. The mechanism behind the development of LVHT in this population remains speculative. Further work is required in this field. Sickle cell patients require longitudinal evaluation to ascertain changes in left ventricular function and the presence of LVHT/noncompaction.

The fate of chemoresistance in triple negative breast cancer (TNBC).

BACKGROUND: Treatment options for women presenting with triple negative breast cancer (TNBC) are limited due to the lack of a therapeutic target and as a result, are managed with standard chemotherapy such as paclitaxel (Taxol®). Following chemotherapy, the ideal tumour response is apoptotic cell death. Post-chemotherapy, cells can maintain viability by undergoing viable cellular responses such as cellular senescence, generating secretomes which can directly enhance the malignant phenotype. SCOPE OF REVIEW: How tumour cells retain viability in response to chemotherapeutic engagement is discussed. In addition we discuss the implications of this retained tumour cell viability in the context of the development of recurrent and metastatic TNBC disease. Current adjuvant and neo-adjuvant treatments available and the novel potential therapies that are being researched are also reviewed. MAJOR CONCLUSIONS: Cellular senescence and cytoprotective autophagy are potential mechanisms of chemoresistance in TNBC. These two non-apoptotic outcomes in response to chemotherapy are inextricably linked and are neglected outcomes of investigation in the chemotherapeutic arena. Cellular fate assessments may therefore have the potential to predict TNBC patient outcome. GENERAL SIGNIFICANCE: Focusing on the fact that cancer cells can bypass the desired cellular apoptotic response to chemotherapy through cellular senescence and cytoprotective autophagy will highlight the importance of targeting non-apoptotic survival pathways to enhance chemotherapeutic efficacy.