Mild Cardiotoxicity and Continued Trastuzumab Treatment in the Context of HER2-Positive Breast Cancer.

Breast cancer is the leading cause of cancer death in women worldwide. Trastuzumab, the main HER2-targeted treatment, faces limitations due to potential cardiotoxicity. The management of patients with mild cardiotoxicity on trastuzumab remains uncertain, resulting in treatment discontinuation and negative oncological outcomes. This retrospective study analyzed 23 patients who experienced decreased left ventricular function during trastuzumab treatment. During the 18-month follow-up period, two patients (9%) had severe declines in function, leading to treatment cessation, and one patient (4%) developed heart failure symptoms. However, 21 patients showed mild, reversible myocardial dysfunction without significant differences in final ventricular function compared to a control group (58.4% vs. 61.7%, respectively; p = 0.059). The declines in function were most pronounced at nine months but improved at twelve and eighteen months. Various echocardiographic parameters changed significantly over time. As predictors of severe cardiotoxicity, we identified the following: LVEF before initial chemotherapy (p = 0.022), as well as baseline LVEF before treatment with trastuzumab (p = 0.007); initial left ventricular end systolic volume (p = 0.027); and the initial global longitudinal strain (p = 0.021) and initial velocity time integral in the left ventricular outflow track (p = 0.027). In conclusion, the continuation of trastuzumab should be considered for most patients with mild cardiotoxicity, with close cardiac monitoring and cardioprotective measures. However, identifying the patients at risk of developing severe cardiotoxicity is necessary. According to our data, the initial LVEF and GLS levels appear to be reliable predictors.

A Composite Sketch of Fast-Spiking Parvalbumin-Positive Neurons.

Parvalbumin-positive neurons are inhibitory neurons that release GABA and are mostly represented by fast-spiking basket or chandelier cells. They constitute a minor neuronal population, yet their peculiar profiles allow them to react quickly to any event in the brain under normal or pathological conditions. In this review, we will summarize the current knowledge about the fundamentals of fast-spiking parvalbumin-positive neurons, focusing on their morphology and specific channel/protein content. Next, we will explore their development, maturation, and migration in the brain. Finally, we will unravel their potential contribution to the physiopathology of epilepsy.

Puzzling Out Synaptic Vesicle 2 Family Members Functions.

Synaptic vesicle proteins 2 (SV2) were discovered in the early 80s, but the clear demonstration that SV2A is the target of efficacious anti-epileptic drugs from the racetam family stimulated efforts to improve understanding of its role in the brain. Many functions have been suggested for SV2 proteins including ions or neurotransmitters transport or priming of SVs. Moreover, several recent studies highlighted the link between SV2 and different neuronal disorders such as epilepsy, Schizophrenia (SCZ), Alzheimer's or Parkinson's disease. In this review article, we will summarize our present knowledge on SV2A function(s) and its potential role(s) in the pathophysiology of various brain disorders.