Plasma miRNA-based signatures in CRC screening programs

Colorectal cancer (CRC) screening programs help diagnose cancer precursors and early cancers and help reduce CRC mortality. However, currently recommended tests, the fecal immunochemical test (FIT) and colonoscopy, have low uptake. There is therefore a pressing need for screening strategies that are minimally invasive and consequently more acceptable to patients, most likely blood based, to increase early CRC identification. MicroRNAs (miRNAs) released from cancer cells are detectable in plasma in a remarkably stable form, making them ideal cancer biomarkers. Using plasma samples from FIT-positive (FIT+) subjects in an Italian CRC screening program, we aimed to identify plasma circulating miRNAs that detect early CRC. miRNAs were initially investigated by quantitative real-time PCR in plasma from 60 FIT+ subjects undergoing colonoscopy at Fondazione IRCCS Istituto Nazionale dei Tumori, then tested on an internal validation cohort (IVC, 201 cases) and finally in a large multicenter prospective series (external validation cohort [EVC], 1121 cases). For each endoscopic lesion (low-grade adenoma [LgA], high-grade adenoma [HgA], cancer lesion [CL]), specific signatures were identified in the IVC and confirmed on the EVC. A two-miRNA-based signature for CL and six-miRNA signatures for LgA and HgA were selected. In a multivariate analysis including sex and age at blood collection, the areas under the receiver operating characteristic curve (95% confidence interval) of the signatures were 0.644 (0.607–0.682), 0.670 (0.626–0.714) and 0.682 (0.580–0.785) for LgA, HgA and CL, respectively. A miRNA-based test could be introduced into the FIT+ workflow of CRC screening programs so as to schedule colonoscopies only for subjects likely to benefit most.     

Hereditary Ataxias in Cuba: A Nationwide Epidemiological and Clinical Study in 1001 Patients

The Cerebellum - The prevalence estimations of hereditary ataxias are biased since most epidemiological studies are confined to isolated geographical regions and few nationwide studies are...     

Neuron types in the zebrafish optic tectum labeled by an id2b transgene

The larval zebrafish optic tectum has emerged as a prominent model for understanding how neural circuits control visually guided behaviors. Further advances in this area will require tools to monitor and manipulate tectal neurons with cell type specificity. Here, we characterize the morphology and neurotransmitter phenotype of tectal neurons labeled by an id2b:gal4 transgene. Whole-brain imaging of stable transgenic id2b:gal4 larvae revealed labeling in a subset of neurons in optic tectum, cerebellum, and hindbrain. Genetic mosaic labeling of single neurons within the id2b:gal4 expression pattern enabled us to characterize three tectal neuron types with distinct morphologies and connectivities. The first is a neuron type previously identified in the optic tectum of other teleost fish: the tectal pyramidal neuron (PyrN). PyrNs are local interneurons that form two stratified dendritic arbors and one stratified axonal arbor in the tectal neuropil. The second tectal neuron type labeled by the id2b:gal4 transgene is a projection neuron that forms a stratified dendritic arbor in the tectal neuropil and an axon that exits tectum to form a topographic projection to torus longitudinalis (TL). A third neuron type labeled is a projection neuron with a nonstratified dendritic arbor and a descending axonal projection to tegmentum. These findings establish the id2b:gal4 transgenic as a useful tool for future studies aimed at elucidating the functional role of tectum, TL, and tegmentum in visually guided behaviors.     

Mechanical Hemolysis Complicating Transcatheter Interventions for Valvular Heart Disease: JACC State-of-the-Art Review

Mechanical intravascular hemolysis is frequently observed following procedures on heart valves and uncommonly observed in native valvular disease. In most cases, its severity is mild. Nevertheless, it can be clinically significant and even life threatening, requiring multiple blood transfusions and renal replacement therapy. This paper reviews the current knowledge on mechanical intravascular hemolysis in valvular disease, before and after correction, focusing on pathophysiology, approach to diagnosis, and impact of other hematological conditions on the resultant anemia. The importance of a multidisciplinary management is underscored. Laboratory data are provided about subclinical hemolysis that is commonly observed following the implantation of surgical and transcatheter valve prostheses and devices. Finally, clinical scenarios are reviewed and current medical and surgical treatments are discussed, including alternative options for inoperable patients.     

Outcomes of patients with non-small cell lung cancer and poor performance status treated with immune checkpoint inhibitors in the real-world setting

International Journal of Clinical Oncology - Immune-checkpoint inhibitors (ICIs) are standard treatments for metastatic non-small cell lung cancer (NSCLC). Patients with poor performance status...