42 research outputs found
The effect of trastuzumab on cardiac function in patients with HER2-positive metastatic breast cancer and reduced baseline left ventricular ejection fraction
We investigated the effect of trastuzumab on cardiac function in a realâworld historic cohort of patients with HER2âpositive metastatic breast cancer (MBC) with reduced baseline left ventricular ejection fraction (LVEF). Thirtyâseven patients with HER2âpositive MBC and baseline LVEF of 40% to 49% were included. Median LVEF was 46% (interquartile range [IQR] 44%â48%) and median followâup was 18âmonths (IQR 9â34âmonths). During this period, the LVEF did not worsen in 24/37 (65%) patients, while 13/37 (35%) patients developed severe cardiotoxicity defined as LVEF 5%âpoints below baseline) in 3/13 (23%) patients and irreversible (defined as absolute LVEF increase 5%âpoints below baseline) in 3/13 (23%) patients. Likelihood of reversibility was numerically higher in patients who received cardioâprotective medications (CPM), including ACEâinhibitors, betaâblockers and angiotensineâ2 inhibitors, compared to those who did not receive any CPM (71% vs 13%, PÂ =Â .091). Sixtyâfive percent of patients who received trastuzumab for HER2âpositive MBC did not develop severe cardiotoxicity during a median followâup of 18âmonths, despite having a compromised baseline LVEF. If severe cardiotoxicity occurred, it was at least partly reversible in more than twoâthirds of the cases. Risks and benefits of trastuzumab use should be balanced carefully in this vulnerable population
Long-term cognitive outcomes in tuberous sclerosis complex.
AIM: To investigate the interdependence between risk factors associated with long-term intellectual development in individuals with tuberous sclerosis complex (TSC). METHOD: The Tuberous Sclerosis 2000 Study is a prospective longitudinal study of individuals with TSC. In phase 1 of the study, baseline measures of intellectual ability, epilepsy, cortical tuber load, and mutation were obtained for 125 children (63 females, 62 males; median age=39mo). In phase 2, at an average of 8 years later, intellectual abilities were estimated for 88 participants with TSC and 35 unaffected siblings. Structural equation modelling was used to determine the risk pathways from genetic mutation through to IQ at phase 2. RESULTS: Intellectual disability was present in 57% of individuals with TSC. Individuals without intellectual disability had significantly lower mean IQ compared to unaffected siblings, supporting specific genetic factors associated with intellectual impairment. Individuals with TSC who had a slower gain in IQ from infancy to middle childhood were younger at seizure onset and had increased infant seizure severity. Structural equation modelling indicated indirect pathways from genetic mutation, to tuber count, to seizure severity in infancy, through to IQ in middle childhood and adolescence. INTERPRETATION: Early-onset and severe epilepsy in the first 2 years of life are associated with increased risk of long-term intellectual disability in individuals with TSC, emphasizing the importance of early and effective treatment or prevention of epilepsy. WHAT THIS PAPER ADDS: Intellectual disability was present in 57% of individuals with tuberous sclerosis complex (TSC). Those with TSC without intellectual disability had significantly lower mean IQ compared to unaffected siblings. Earlier onset and greater severity of seizures in the first 2 years were observed in individuals with a slower gain in intellectual ability. Risk pathways through seizures in the first 2 years predict long-term cognitive outcomes in individuals with TSC