Ken Grauer, MD
DECEMBER 15, 2023
== CLICK HERE — for a V ideo presentation of this case! ( 18:00 min. ) Below are slides used in my video presentation. For full discussion of this case — See ECG Blog #392 — == The ECG in Figure-1 was obtained from a man in his 60s — who described the sudden onset of "chest tightness" that began 20 minutes earlier, but who now ( at the time this ECG was recorded ) — was no longer having symptoms.
Journal of Clinical Investigation - Cardiology
DECEMBER 15, 2023
Ghrelin exerts key effects on islet hormone secretion to regulate blood glucose levels. Here, we sought to determine whether ghrelin’s effects on islets extend to the alteration of islet size and β cell mass. We demonstrate that reducing ghrelin — by ghrelin gene knockout (GKO), conditional ghrelin cell ablation, or high-fat diet (HFD) feeding — was associated with increased mean islet size (up to 62%), percentage of large islets (up to 854%), and β cell cross-sectional area (up to 51%).
HCPLive
DECEMBER 15, 2023
Laura Donlin, PhD, highlights the significance of identifying new subtypes of rheumatoid arthritis, emphasizing the potential for a paradigm shift in RA treatment toward personalized care and early interventions.
Journal of Clinical Investigation - Cardiology
DECEMBER 15, 2023
A paucity of chemotherapeutic options for metastatic brain cancer limits patient survival and portends poor clinical outcomes. Using a CNS small-molecule inhibitor library of 320 agents known to be blood-brain barrier permeable and approved by the FDA, we interrogated breast cancer brain metastasis vulnerabilities to identify an effective agent. Metixene, an antiparkinsonian drug, was identified as a top therapeutic agent that was capable of decreasing cellular viability and inducing cell death
HCPLive
DECEMBER 15, 2023
The past year has seen a multitude of FDA approvals, ranging from IL-23 and JAK inhibitors to biologics and subcutaneous treatment administrations, that have helped redefine what it means to treat IBD.
Journal of Clinical Investigation - Cardiology
DECEMBER 15, 2023
Cell therapies such as tumor-infiltrating lymphocyte (TIL) therapy have shown promise in the treatment of patients with refractory solid tumors, with improvement in response rates and durability of responses nevertheless sought. To identify targets capable of enhancing the antitumor activity of T cell therapies, large-scale in vitro and in vivo clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 screens were performed, with the SOCS1 gene identified as a top T cell–enhancing
Med Page Today
DECEMBER 15, 2023
(MedPage Today) -- Patients living in more disadvantaged neighborhoods were more likely to leave their prescriptions for standard heart failure medications unfilled, retrospective data from a large health system showed. Among patients with heart.
Cardiovascular Update brings together the best content for cardiovascular medicine professionals from the widest variety of industry thought leaders.
HCPLive
DECEMBER 15, 2023
In a phase 3 EMERGENT-2 trial, the study found 55% of participants with schizophrenia taking xanomeline-trospium had a ≥30% improvement from baseline to week 5, compared to the placebo group.
Journal of Clinical Investigation - Cardiology
DECEMBER 15, 2023
A20 is a ubiquitin-modifying protein that negatively regulates NF-κB signaling. Mutations in A20/TNFAIP3 are associated with a variety of autoimmune diseases, including multiple sclerosis (MS). We found that deletion of A20 in central nervous system (CNS) endothelial cells (ECs) enhances experimental autoimmune encephalomyelitis (EAE), a mouse model of MS.
Science Daily - Heart Disease
DECEMBER 15, 2023
Researchers have discovered that a certain kind of protein similar to hemoglobin, called cytoglobin, plays an important role in the development of the heart. Specifically, it affects the correct left-right pattern of the heart and other asymmetric organs. The findings could eventually lead to the development of new therapeutic interventions to alter the processes that lead to these defects.
Journal of Clinical Investigation - Cardiology
DECEMBER 15, 2023
Metabolic syndrome, today affecting more than 20% of the US population, is a group of 5 conditions that often coexist and that strongly predispose to cardiovascular disease. How these conditions are linked mechanistically remains unclear, especially two of these: obesity and elevated blood pressure. Here, we show that high fat consumption in mice leads to the accumulation of lipid droplets in endothelial cells throughout the organism and that lipid droplet accumulation in endothelium suppresses
HCPLive
DECEMBER 15, 2023
Califf joins HCPLive to share perspective on AI, gene and cell therapy development, COVID-19, food and substance regulation, maternal and infant health, weight loss intervention, and more.
Journal of Clinical Investigation - Cardiology
DECEMBER 15, 2023
Protein synthesis is frequently dysregulated in cancer and selective inhibition of mRNA translation represents an attractive cancer therapy. Here, we show that therapeutically targeting the RNA helicase eIF4A with zotatifin, the first-in-class eIF4A inhibitor, exerts pleiotropic effects on both tumor cells and the tumor immune microenvironment in a diverse cohort of syngeneic triple-negative breast cancer (TNBC) mouse models.
Medical Xpress - Cardiology
DECEMBER 15, 2023
In a study led by the University of Maryland School of Medicine, researchers discovered for the first time that a certain kind of protein similar to hemoglobin, called cytoglobin, plays an important role in the development of the heart. Specifically, it affects the correct left-right pattern of the heart and other asymmetric organs.
Journal of Clinical Investigation - Cardiology
DECEMBER 15, 2023
We previously demonstrated that a subset of acute myeloid leukemia (AML) patients with concurrent RAS pathway and TP53 mutations have an extremely poor prognosis and that most of these TP53 mutations are missense mutations. Here, we report that, in contrast to the mixed AML and T cell malignancy that developed in NrasG12D/+ p53–/– (NP–/–) mice, NrasG12D/+ p53R172H/+ (NPmut) mice rapidly developed inflammation-associated AML.
The New England Journal of Medicine
DECEMBER 15, 2023
Hypotension developed in a 14-year-old boy after pericardiocentesis. An echocardiogram (shown in a video) revealed new right ventricular dilatation, biventricular systolic dysfunction, and severe tricuspid regurgitation.
Journal of Clinical Investigation - Cardiology
DECEMBER 15, 2023
Reactivation and dysregulation of the mTOR signaling pathway are a hallmark of aging and chronic lung disease; however, the impact on microvascular progenitor cells (MVPCs), capillary angiostasis, and tissue homeostasis is unknown. While the existence of an adult lung vascular progenitor has long been hypothesized, these studies show that Abcg2 enriches for a population of angiogenic tissue-resident MVPCs present in both adult mouse and human lungs using functional, lineage, and transcriptomic a
Stroke Journal
DECEMBER 15, 2023
Stroke, Ahead of Print. Intracerebral hemorrhage is the most serious type of stroke, leading to high rates of severe disability and mortality. Hematoma expansion is an independent predictor of poor functional outcome and is a compelling target for intervention. For decades, randomized trials aimed at decreasing hematoma expansion through single interventions have failed to meet their primary outcomes of statistically significant improvement in neurological outcomes.
Journal of Clinical Investigation - Cardiology
DECEMBER 15, 2023
Activation of TGF-β signaling serves as an extrinsic resistance mechanism that limits the potential for radiotherapy. Bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) antagonizes TGF-β signaling and is implicated in cancer progression. However, the molecular mechanisms of BAMBI regulation in immune cells and its impact on antitumor immunity after radiation have not been established.
Becker's Hospital Review - Cardiology
DECEMBER 15, 2023
Experts have long known that where a patient lives can have an effect on health outcomes, but a new study from NYU Langone finds that it can also affect how likely a patient is to fill their prescription for heart failure medications.
Journal of Clinical Investigation - Cardiology
DECEMBER 15, 2023
Foxp3-expressing Tregs employ multiple suppressive mechanisms to curtail conventional T cell (Tconv) responses and establish tissue homeostasis. How Foxp3 coordinates Treg contact–dependent suppressive function is not fully resolved. In this issue of the JCI, Wang and colleagues revealed that Foxp3-mediated inhibition of ryanodine receptor 2 (RyR2) led to strong Treg-DC interactions and enhanced immunosuppression.
American College of Cardiology
DECEMBER 15, 2023
The following are key points to remember from a state-of-the-art paper on current and evolving multimodality cardiac imaging in managing transthyretin amyloid cardiomyopathy.
Journal of Clinical Investigation - Cardiology
DECEMBER 15, 2023
Tumor burden, considered a common chronic stressor, can cause widespread anxiety. Evidence suggests that cancer-induced anxiety can promote tumor progression, but the underlying neural mechanism remains unclear. Here, we used neuroscience and cancer tools to investigate how the brain contributes to tumor progression via nerve-tumor crosstalk in a mouse model of breast cancer.
Frontiers in Cardiovascular Medicine
DECEMBER 15, 2023
Background Atrial fibrillation (AF) is a common cardiac arrhythmia that increases the risk of stroke and other cardiovascular complications. Oral anticoagulants (OACs) are effective in reducing this risk. To investigate the knowledge, attitude and practice (KAP) toward OACs among patients with AF. Methods This web-based cross-sectional study was conducted at local Hospital between April 2023 and May 2023, and enrolled AF patients.
Journal of Clinical Investigation - Cardiology
DECEMBER 15, 2023
Tissue-resident lymphocytes provide organ-adapted protection against invading pathogens. Whereas their biology has been examined in great detail in various infection models, their generation and functionality in response to vaccination have not been comprehensively analyzed in humans. We therefore studied SARS-CoV-2 mRNA vaccine–specific T cells in surgery specimens of kidney, liver, lung, bone marrow, and spleen compared with paired blood samples from largely virus-naive individuals.
Dr. Smith's ECG Blog
DECEMBER 15, 2023
This is by Magnus Nossen, from Norway The patient is a 70 something male with a hx of hypertension and tobacco use disorder. He is otherwise healthy. The patient contacted EMS after a few hours of chest pain that started 5:30 AM. The pain was described as 6/10 radiating to the right shoulder. Vital signs were within normal limits, and the patient was not ill appearing.
Journal of Clinical Investigation - Cardiology
DECEMBER 15, 2023
The G protein–coupled receptor 84 (GPR84), a medium-chain fatty acid receptor, has garnered attention because of its potential involvement in a range of metabolic conditions. However, the precise mechanisms underlying this effect remain elusive. Our study has shed light on the pivotal role of GPR84, revealing its robust expression and functional significance within brown adipose tissue (BAT).
HCPLive
DECEMBER 15, 2023
Rheumatoid arthritis and its treatment can increase the risk of cardiovascular events. Test your knowledge of how risk of serious cardiovascular events is affected by RA treatments with this quiz.
Journal of Clinical Investigation - Cardiology
DECEMBER 15, 2023
The suppression mechanism of Tregs remains an intensely investigated topic. As our focus has shifted toward a model centered on indirect inhibition of DCs, a universally applicable effector mechanism controlled by the transcription factor forkhead box P3 (Foxp3) expression has not been found. Here, we report that Foxp3 blocked the transcription of ER Ca2+-release channel ryanodine receptor 2 (RyR2).
HCPLive
DECEMBER 15, 2023
A phase 2b clinical trial met its primary endpoint with positive topline results, showing MM-120 (lysergide d-tartrate) can reduce symptoms of generalized anxiety disorder, reflected in the Hamilton Anxiety rating scale scores.
Journal of Clinical Investigation - Cardiology
DECEMBER 15, 2023
Heart failure with preserved ejection fraction (HFpEF) is a widespread syndrome with limited therapeutic options and poorly understood immune pathophysiology. Using a 2-hit preclinical model of cardiometabolic HFpEF that induces obesity and hypertension, we found that cardiac T cell infiltration and lymphoid expansion occurred concomitantly with cardiac pathology and that diastolic dysfunction, cardiomyocyte hypertrophy, and cardiac phospholamban phosphorylation were T cell dependent.
HCPLive
DECEMBER 15, 2023
The New Drug Application submission is supported by data from a pair of phase 3 studies, a long-term open-label study, and prior phase 2 studies. Cymabay has also requested Priority Review of the NDA.
Journal of Clinical Investigation - Cardiology
DECEMBER 15, 2023
Elevation of reactive oxygen species (ROS) levels is a general consequence of tumor cells’ response to treatment and may cause tumor cell death. Mechanisms by which tumor cells clear fatal ROS, thereby rescuing redox balance and entering a chemoresistant state, remain unclear. Here, we show that cysteine sulfenylation by ROS confers on aryl hydrocarbon receptor (AHR) the ability to dissociate from the heat shock protein 90 complex but to bind to the PPP1R3 family member PPP1R3C of the glycogen c
HCPLive
DECEMBER 15, 2023
This announcement may be considered further progress in the implementation of the FDA Overdose Prevention Framework designed to prevent overdoses and reduce mortality.
Journal of Clinical Investigation - Cardiology
DECEMBER 15, 2023
Strategies for patient stratification and early intervention are required to improve clinical benefits for patients with prostate cancer. Here, we found that active DHEA utilization in the prostate gland correlated with tumor aggressiveness at early disease stages, and 3βHSD1 inhibitors were promising for early intervention. [3H]-labeled DHEA consumption was traced in fresh prostatic biopsies ex vivo.
HCPLive
DECEMBER 15, 2023
These data indicate that the early detection of vitiligo may be improved through an assessment of transplant recipients and using a multidisciplinary approach.
Physiologically Speaking
DECEMBER 15, 2023
Greetings! Welcome to the Physiology Friday newsletter. This newsletter is brought to you by Examine.com — the best place on the internet for health and nutrition information — and my new eBook, “VO2 Max Essentials.” Details can be found at the end of the post! Physiologically Speaking is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber.
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