Attempted Cardiopulmonary Bypass Venous Cannula Extraction Catheter Extraction of a Rare Intracardiac Myoepithelioma.

Myoepithelioma of the soft tissue is a rare entity that can mimic myxoma when presenting within the heart. We present a case where cardiopulmonary bypass venous cannula extraction catheter removal of an intracardiac myoepithelioma was attempted with minimal debulking and subsequently required minimally invasive open-heart surgery with cardiopulmonary bypass. ().

Multicenter validation of a machine learning phase space electro-mechanical pulse wave analysis to predict elevated left ventricular end diastolic pressure at the point-of-care.

Background: Phase space is a mechanical systems approach and large-scale data representation of an object in 3-dimensional space. Whether such techniques can be applied to predict left ventricular pressures non-invasively and at the point-of-care is unknown.

Objective: This study prospectively validated a phase space machine-learned approach based on a novel electro-mechanical pulse wave method of data collection through orthogonal voltage gradient (OVG) and photoplethysmography (PPG) for the prediction of elevated left ventricular end diastolic pressure (LVEDP).

Identifying novel phenotypes of elevated left ventricular end diastolic pressure using hierarchical clustering of features derived from electromechanical waveform data.

Introduction: Elevated left ventricular end diastolic pressure (LVEDP) is a consequence of compromised left ventricular compliance and an important measure of myocardial dysfunction. An algorithm was developed to predict elevated LVEDP utilizing electro-mechanical (EM) waveform features. We examined the hierarchical clustering of selected features developed from these EM waveforms in order to identify important patient subgroups and assess their possible prognostic significance.

Extreme Angiographic-Physiologic Mismatch With Elevated Left Ventricular End-Diastolic Pressure.

Translesional coronary pressure measures the hemodynamic significance of epicardial coronary artery disease. Angiographic-physiologic mismatching is attributed mainly to imaging limitations. We present a patient with extreme visual-physiologic functional mismatch and a markedly elevated left ventricular end diastolic pressure (LVEDP) as a potential contributory mechanism.

Toward precision health: applying artificial intelligence analytics to digital health biometric datasets.

The rapid development of digital health devices has enabled patients to engage in their care to an unprecedented degree and holds the possibility of significantly improving the diagnosis, treatment and monitoring of many medical conditions. Combined with the emergence of artificial intelligence algorithms, biometric datasets produced from these digital health devices present new opportunities to create precision-based, personalized approaches for healthcare delivery. For effective implementation of such innovations to patient care, clinicians will require an understanding of the types of datasets produced from digital health technologies; the types of analytic methods including feature selection, convolution neural networking, and deep learning that can be used to analyze digital data; and how the interpretation of these findings are best translated to patient care.

D-2-hydroxyglutarate produced by mutant IDH2 causes cardiomyopathy and neurodegeneration in mice.

Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) have been discovered in several cancer types and cause the neurometabolic syndrome D2-hydroxyglutaric aciduria (D2HGA). The mutant enzymes exhibit neomorphic activity resulting in production of D2-hydroxyglutaric acid (D-2HG). To study the pathophysiological consequences of the accumulation of D-2HG, we generated transgenic mice with conditionally activated IDH2(R140Q) and IDH2(R172K) alleles.

Activation of the PD-1 pathway contributes to immune escape in EGFR-driven lung tumors.

Unlabelled: The success in lung cancer therapy with programmed death (PD)-1 blockade suggests that immune escape mechanisms contribute to lung tumor pathogenesis. We identified a correlation between EGF receptor (EGFR) pathway activation and a signature of immunosuppression manifested by upregulation of PD-1, PD-L1, CTL antigen-4 (CTLA-4), and multiple tumor-promoting inflammatory cytokines. We observed decreased CTLs and increased markers of T-cell exhaustion in mouse models of EGFR-driven lung cancer.

Efficacy of BET bromodomain inhibition in Kras-mutant non-small cell lung cancer.

Purpose: Amplification of MYC is one of the most common genetic alterations in lung cancer, contributing to a myriad of phenotypes associated with growth, invasion, and drug resistance. Murine genetics has established both the centrality of somatic alterations of Kras in lung cancer, as well as the dependency of mutant Kras tumors on MYC function. Unfortunately, drug-like small-molecule inhibitors of KRAS and MYC have yet to be realized.

Metabolic and functional genomic studies identify deoxythymidylate kinase as a target in LKB1-mutant lung cancer.

The LKB1/STK11 tumor suppressor encodes a serine/threonine kinase, which coordinates cell growth, polarity, motility, and metabolism. In non-small cell lung carcinoma, LKB1 is somatically inactivated in 25% to 30% of cases, often concurrently with activating KRAS mutations. Here, we used an integrative approach to define novel therapeutic targets in KRAS-driven LKB1-mutant lung cancers.

Synthetic lethal interaction of combined BCL-XL and MEK inhibition promotes tumor regressions in KRAS mutant cancer models.

KRAS is the most commonly mutated oncogene, yet no effective targeted therapies exist for KRAS mutant cancers. We developed a pooled shRNA-drug screen strategy to identify genes that, when inhibited, cooperate with MEK inhibitors to effectively treat KRAS mutant cancer cells. The anti-apoptotic BH3 family gene BCL-XL emerged as a top hit through this approach.