Mon.Dec 02, 2024

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Transcription factor KROX20 marks epithelial stem cell ancestors for hair follicle formation

Journal of Clinical Investigation - Cardiology

Epidermal stem cells control homeostasis and regeneration of skin and hair. In the hair follicle (HF) bulge of mammals, populations of slow-cycling stem cells regenerate the HF during cyclical rounds of anagen (growth), catagen (regression), and telogen (quiescence). Multipotent epidermal cells are also present in the HF above the bulge area, contributing to the formation and maintenance of sebaceous gland and upper and middle portions of the HF.

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Intermountain hospital earns vascular recognition

Becker's Hospital Review - Cardiology

Salt Lake City-based Intermountain Health's St. Mary's Regional Hospital in Grand Junction, Colo., has become the first community hospital in the nation to receive vascular verification from the American College of Surgeons and the Society for Vascular Surgery.

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PCDH15 dual-AAV gene therapy for deafness and blindness in Usher syndrome type 1F models

Journal of Clinical Investigation - Cardiology

Usher syndrome type 1F (USH1F), resulting from mutations in the protocadherin-15 (PCDH15) gene, is characterized by congenital lack of hearing and balance, and progressive blindness in the form of retinitis pigmentosa. In this study, we explore an approach for USH1F gene therapy, exceeding the single AAV packaging limit by employing a dual–adeno-associated virus (dual-AAV) strategy to deliver the full-length PCDH15 coding sequence.

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Newfound mechanism may explain why some cancer treatments boost risk of heart disease

Science Daily - Heart Disease

A cancer therapy that prompts the body's immune defenses against viruses and bacteria to attack tumors can make patients more vulnerable to heart attack and stroke. A possible explanation for this side effect is that the treatment interferes with immune regulation in the heart's largest blood vessels, a new study suggests.

Cancer 89
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Reactive microglia partially envelop viable neurons in prion diseases

Journal of Clinical Investigation - Cardiology

Microglia are recognized as the main cells in the central nervous system responsible for phagocytosis. The current study demonstrates that in prion disease, microglia effectively phagocytose prions or PrPSc during early preclinical stages. However, a critical shift occurred in microglial activity during the late preclinical stage, transitioning from PrPSc uptake to establishing extensive neuron-microglia body-to-body cell contacts.

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Higher ratio of plant protein to animal protein may improve heart health

Science Daily - Heart Disease

Eating a diet with a higher ratio of plant-based protein to animal-based protein may reduce the risk of cardiovascular disease (CVD) and coronary heart disease (CHD), according to a new study. According to the researchers, these risk reductions are likely driven by the replacement of red and processed meats with plant proteins. The researchers also observed that a combination of consuming more plant protein and higher protein intake overall provided the most heart health benefits.

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Nonclassical action of Ku70 promotes Treg-suppressive function through a FOXP3-dependent mechanism in lung adenocarcinoma

Journal of Clinical Investigation - Cardiology

Ku70, a DNA repair protein, binds to the damaged DNA ends and orchestrates the recruitment of other proteins to facilitate repair of DNA double-strand breaks. Besides its essential role in DNA repair, several studies have highlighted nonclassical functions of Ku70 in cellular processes. However, its function in immune homeostasis and antitumor immunity remains unknown.

Cancer 98

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The Nr4a family regulates intrahepatic Treg proliferation and liver fibrosis in MASLD models

Journal of Clinical Investigation - Cardiology

Metabolic dysfunction–associated steatotic hepatitis (MASH) is a chronic progressive liver disease that is highly prevalent worldwide. MASH is characterized by hepatic steatosis, inflammation, fibrosis, and liver damage, which eventually result in liver dysfunction due to cirrhosis or hepatocellular carcinoma. However, the cellular and molecular mechanisms underlying MASH progression remain largely unknown.

Diet 98
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FDA Receives sBLA for Guselkumab Treatment of Psoriasis, Juvenile PsA in Adolescents

HCPLive

Two supplemental Biologics License Applications for guselkumab were submitted to the FDA for treatment of children with plaque psoriasis and active juvenile psoriatic arthritis.

Plaque 64
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Reduced thymic IL-4 impairs negative T cell selection in nonobese diabetic mice

Journal of Clinical Investigation - Cardiology

Type 1 diabetes (T1D) develops spontaneously despite functional antigen presentation machinery in the thymus and a perceptible central tolerance process. We found that intrathymic enrichment with IL-4 fine tunes signaling through the IL-4/IL-13 heteroreceptor (HR) in early thymic progenitors (ETPs), augments negative selection of self-reactive T cells, sustains a diverse T cell repertoire devoid of clones expressing disease-associated T cell receptor (TCR) genes, and protects the nonobese diabet

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Anaphylm Sublingual Film for Anaphylaxis Receives Positive FDA Feedback

HCPLive

The FDA affirmed the planned NDA content and format for Anaphylm expected in Q1 2025, without requiring additional adult clinical trials before submission.

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GLP-1s and heart outcomes: 5 recent findings

Becker's Hospital Review - Cardiology

With deaths from obesity-related heart disease reportedly increasing by 180% over the past 20 years, more research is being done to learn how GLP-1 medications such as Ozempic, Wegovy, Mounjaro and Zepbound can address outcomes in cardiovascular health.

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HO-1 impairs the efficacy of radiotherapy by redistributing cGAS and STING in tumors

Journal of Clinical Investigation - Cardiology

Type I IFNs (IFN-Is) induced by radiotherapy (RT) are critical for its efficacy, while the mechanism by which tumor cells inhibit IFN-I production remains largely unsolved. By an unbiased CRISPR screen, we identified hemeoxygenase 1 (HO-1) as an RT-related regulator of IFN-I production. Mechanistically, the ER-anchored, full-length HO-1 disrupted stimulator of IFN genes (STING) polymerization and subsequent coat protein complex II–mediated (COPII-mediated) ER-Golgi transportation, leading to ham

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Trials and tribulations of cell therapy for heart failure, an update on ongoing trials

Science Daily - Heart Disease

A critical review of cell-based and cell product-based therapies for the treatment of heart failure details 20 years of completed and ongoing clinical trials. While none has yet gained medical approval, pathways to new treatments for heart failure can take decades, as seen for two other, now accepted therapies.

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Community-Based Trial of Compression Tights in POTS

American College of Cardiology

What is the ability of commercially available waist-high compression (WHC) garments to reduce heart rate and improve symptoms in patients with postural orthostatic tachycardia syndrome (POTS) in a community setting?

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Physiology Friday November Recap

Physiologically Speaking

Greetings! In case you missed it, here are all of the studies I covered in the November 2024 installments of the Physiology Friday newsletter. Enjoy (or re-enjoy) these summaries, and don’t forget to share them with someone you think might learn from or be interested in them. Thanks for reading! Physiologically Speaking is a reader-supported publication.

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FDA Clears Initiation of Phase 2 Efficacy Trial for Ruxoprubart in IgAN

HCPLive

As announced by NovelMed on December 2, 2024, the FDA has granted IND clearance for Ruxoprubart to commence an efficacy trial for the treatment of IgAN.

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Effect of optimisation to contemporary HFrEF medical therapy with sacubitril/valsartan (Entresto) and dapaglifloziN on left Ventricular reverse remodelling as demonstrated by cardiac magnetic resonance (CMR) Imaging: the ENVI study

Open Heart

Introduction Heart failure with reduced ejection fraction (HFrEF) guidelines recommend ‘four pillars’ of medical therapy and device therapy if left ventricular ejection fraction (LVEF) remains ≤35% after 3 months optimum medical therapy. We conducted the first study to examine the effects of optimisation to contemporary medical therapy on cardiac reverse remodelling, as demonstrated by cardiac magnetic resonance imaging (CMR).

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FDA Approves Ustekinumab (STELARA) Biosimilar for Crohn’s, UC, Psoriasis, PsA

HCPLive

Ustekinumab-kfce is planned for launch in February 2025 according to a previous settlement and license agreement with Janssen.

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Aspirin in Patients With DES Undergoing Noncardiac Surgery

American College of Cardiology

Is there a benefit to perioperative continuation of aspirin in patients with coronary drug-eluting stents (DES) undergoing noncardiac surgery?

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SGLT2 inhibitors, RAAS inhibitors, nsMRAs, & GLP-1 receptor Agonists

HCPLive

Panelists discuss how SGLT2 inhibitors, RAAS inhibitors, and GLP-1 receptor agonists differ in their treatment of chronic kidney disease (CKD) in patients with type 2 diabetes, along with strategies for managing hyperkalemia in patients to help them resume their treatment course.

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For the FITs | Diversity in Clinical Trials: How FITs Can Help

American College of Cardiology

I do not want to be a lab rat. This is what a patient who self-identified as Black told me when I attempted to obtain his approval to discuss his case and allow a physical examination during our fellowship weekly bedside teaching rounds.

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Misdiagnosis and Barriers to Early Detection of IgAN

HCPLive

Panelists discuss how misdiagnosis and delayed diagnosis of IgA nephropathy occur, highlighting the primary barriers to timely detection and strategies to overcome these challenges.

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Cover Story | Takotsubo Syndrome: Expanding Insights, Unanswered Questions

American College of Cardiology

Between 2% to 3% of all patients and 5% to 6% of all women who present with what looks like an acute coronary syndrome (ACS) are actually suffering from a peculiar and reversible acute cardiac condition, not caused by epicardial coronary obstruction, called takotsubo syndrome (TTS).

Article 56
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Genital Mycotic Infection Treatment and Adverse Effects

HCPLive

Panelists discuss the treatment of a patient with type 2 diabetes who develops a genital mycotic infection while on an SGLT-2 inhibitor, weighing the options of treating with topical antifungals versus discontinuing the medication, as well as addressing concerns for a patient on a GLP-1 receptor agonist and RAAS inhibitor who is experiencing adverse effects such as bloating and nausea while considering the benefits of continuing therapy.

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To Continue or Not Continue: Beta-Blockers Following Acute Myocardial Infarction

American College of Cardiology

Current guidelines regarding beta-blocker use after myocardial infarction (MI) recommend against continuation to improve outcomes after 1 year, in the absence of reduced left ventricular ejection fraction (LVEF; <50%) or other primary indications for therapy.

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Differential Diagnoses of IgAN

HCPLive

Panelists discuss how clinicians can differentiate IgA nephropathy from other glomerular diseases, such as lupus nephritis and membranous nephropathy, that may present with similar clinical features.

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Supportive care or exhausted neglect: the role of microglia at the end stage of prion disease

Journal of Clinical Investigation - Cardiology

The transmissible nature of prion diseases enables reproduction of neurodegeneration in small animal models that faithfully follows the disease process observed in the natural disease of animals and humans. This allows the temporal development of disease to be investigated and correlated with pathology in a complex brain environment. In this issue of the JCI, Makarava et al. describe a shift in microglia morphology from an active phagocytic phenotype to a passive association with neuronal cell b

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The APAC Recap: Peripheral Artery Disease at CAPP Live 2024 with Bob Ross, PA-C

HCPLive

Bob Ross, PA-C, shares expert insights on early PAD detection, updated guidelines, and practical tools to improve vascular health outcomes from CAPP 2024.

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ACC 2025 Medicare Physician Fee Schedule Final Rule Calculator Now Available

American College of Cardiology

Work, practice, expense and liability relative value units (RVUs) are updated annually through the Centers for Medicare and Medicaid Services' Medicare Physician Fee Schedule (PFS) rulemaking.

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How to Manage Aspirin-Exacerbated Respiratory Disease

HCPLive

This portion of the latest Lungcast episode includes a discussion of therapies, triggers, and management of AERD.

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Taking the STING out of radiotherapy: STING checkpoints mediate radiation resistance

Journal of Clinical Investigation - Cardiology

The cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS/STING) pathway is a critical driver of type I interferon (IFN-I) and antitumor CD8+ T cell responses after radiotherapy (RT). In this issue of the JCI, two reports describe mechanisms that restrained STING signaling and abrogated antitumor immunity after RT. Wen, Wang, and colleagues discovered that IFN-I mediated the induction of YTHDF1, an RNA N6-methyladenosine–binding protein, in DCs after RT promoted cathepsin-mediated STING d

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From the Member Sections | Transformative Trends Shaping the Future of the Business of Cardiology

American College of Cardiology

Cardiovascular medicine is at a crossroads, navigating the dual pressures of an aging population and an evolving health care landscape. The business of cardiology, in particular, is being reshaped by a myriad of cultural and technological trends.

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Diuretic efficiency of a single dose of subcutaneous versus oral furosemide after heart failure hospitalization across diuretic resistance strata: A pilot randomized controlled trial

European Journal of Heart Failure

Aims Diuretic resistance (DR) in heart failure (HF) is associated with worse outcomes. Furoscix®, a self-administered subcutaneous (sc) furosemide injection administered via on-body infusor, is approved for HF congestion relief. However, its efficacy in patients with DR post-HF hospitalization remains unknown. Methods and results In this open-label pilot randomized controlled trial, 70 participants were randomized within 14 days post-HF hospitalization to receive a single dose of 80 mg sc furose

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New in Clinical Guidance | Contemporary Training in CCC

American College of Cardiology

Critical care cardiology (CCC) requires specialized and advanced training. A comprehensive guide for current trainees, along with insights about the present landscape of CCC, as well as issues to be addressed for continued advancement were the focus of a recent JACC Scientific Expert Panel.

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CineECG Repolarization Gradients Predict Acute Hemodynamic Response in CRT Patients

Journal of Cardiovascular Electrophysiology

ABSTRACT Introduction A variable proportion of non-responders to cardiac resynchronization therapy (CRT) warrants the search for new approaches to optimize the position of the left ventricular (LV) lead and the CRT device programming. CineECG is a novel ECG modality proposed for the spatial visualization and quantification of myocardial depolarization and repolarization sequences.

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Feature | ACC Education: Always Innovating. Always Learning.

American College of Cardiology

For 75 years, the ACC has led in providing cutting-edge, innovative education to cardiovascular clinicians, ensuring they have the latest knowledge and skills to optimize patient care and outcomes. This month, Cardiology highlights three examples of ACC Education in action.