HER2 status in advanced gastric cancer: the dark side of the moon

The present study evaluated HER2 status between primary gastric and paired metastatic disease to lymph nodes, collecting 62 formalin-fixed paraffin-embedded representative tissue blocks as well as synchronous metastatic lymph nodes by immunohistochemistry and FISH. The discordant HER2 pooled rate, regardless either negative or positive conversion, was 9.26% in primary gastric carcinoma and corresponding nodal metastasis. Moreover, a high level concordance in HER2 expression between primary carcinoma and synchronous metastatic lymph nodes was achieved in 90.74% of cases. In our opinion, the observed event of discordant HER2 status should be ascribed to intra-tumor heterogeneity. In any case, the shift from positive to negative HER2 expression suggests that Trastuzumab could be the targeted treatment choice, while the opposite shift should be evaluated by a simultaneous HER2 determination in both primary and metastatic lymph nodes

Loss of Neuron Navigator 2 Impairs Brain and Cerebellar Development

Acknowledgements We thank the study family for their enthusiastic participationPeer reviewedPublisher PD

Fibrosis after Myocardial Infarction: An Overview on Cellular Processes, Molecular Pathways, Clinical Evaluation and Prognostic Value

The ischemic injury caused by myocardial infarction activates a complex healing process wherein a powerful inflammatory response and a reparative phase follow and balance each other. An intricate network of mediators finely orchestrate a large variety of cellular subtypes throughout molecular signaling pathways that determine the intensity and duration of each phase. At the end of this process, the necrotic tissue is replaced with a fibrotic scar whose quality strictly depends on the delicate balance resulting from the interaction between multiple actors involved in fibrogenesis. An inflammatory or reparative dysregulation, both in term of excess and deficiency, may cause ventricular dysfunction and life-threatening arrhythmias that heavily affect clinical outcome. This review discusses cellular process and molecular signaling pathways that determine fibrosis and the imaging technique that can characterize the clinical impact of this process in-vivo

Gliflozins: From Antidiabetic Drugs to Cornerstone in Heart Failure Therapy—A Boost to Their Utilization and Multidisciplinary Approach in the Management of Heart Failure

Heart failure (HF) is a complex, multifactorial, progressive clinical condition affecting 64.3 million people worldwide, with a strong impact in terms of morbidity, mortality and public health costs. In the last 50 years, along with a better understanding of HF physiopathology and in agreement with the four main models of HF, many therapeutic options have been developed. Recently, the European Society of Cardiology (ESC) HF guidelines enthusiastically introduced inhibitors of the sodium-glucose cotransporter (SGLT2i) as first line therapy for HF with reduced ejection fraction (HFrEF) in order to reduce hospitalizations and mortality. Despite drugs developed as hypoglycemic agents, data from the EMPA-REG OUTCOME trial encouraged the evaluation of the possible cardiovascular effects, showing SGLT2i beneficial effects on loading conditions, neurohormonal axes, heart cells’ biochemistry and vascular stiffness, determining an improvement of each HF model. We want to give a boost to their use by increasing the knowledge of SGLT2-I and understanding the probable mechanisms of this new class of drugs, highlighting strengths and weaknesses, and providing a brief comment on major trials that made Gliflozins a cornerstone in HF therapy. Finally, aspects that may hinder SGLT2-i widespread utilization among different types of specialists, despite the guidelines’ indications, will be discussed