TRPM7 channel activity promotes the pathogenesis of abdominal aortic aneurysms
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Deep learning to predict cardiovascular mortality from aortic disease in heavy smokers
Aortic angiopathy is a common manifestation of cardiovascular disease (CVD) and may serve as a surrogate marker of CVD burden. While the maximum aortic diameter is the primary prognostic measure, the potential of other features to improve risk prediction remains uncertain. This study developed a deep learning framework to automatically quantify thoracic aortic disease features and assessed their prognostic value in predicting CVD mortality among heavy smokers. Using non-contrast chest CTs from the National Lung Screening Trial (NLST), aortic features quantified included maximum diameter, volume, and calcification burden. Among 24,770 participants, 440 CVD deaths occurred over a mean 6.3-year follow-up. Aortic calcifications and volume were independently associated with CVD mortality, even after adjusting for traditional risk factors and coronary artery calcifications. These findings suggest that deep learning-derived aortic features could improve CVD risk prediction in high-risk populations, enabling more personalized prevention strategies.
A UK population-based case-control study of blood tests before cancer diagnosis in patients with non-specific abdominal symptoms
Abnormal results in commonly used primary care blood tests could be early markers of cancer in patients presenting with non-specific abdominal symptoms.
Ion channel traffic jams: the significance of trafficking deficiency in long QT syndrome
A well-balanced ion channel trafficking machinery is paramount for the normal electromechanical function of the heart. Ion channel variants and many drugs can alter the cardiac action potential and lead to arrhythmias by interfering with mechanisms like ion channel synthesis, trafficking, gating, permeation, and recycling. A case in point is the Long QT syndrome (LQTS), a highly arrhythmogenic disease characterized by an abnormally prolonged QT interval on ECG produced by variants and drugs that interfere with the action potential. Disruption of ion channel trafficking is one of the main sources of LQTS. We review some molecular pathways and mechanisms involved in cardiac ion channel trafficking. We highlight the importance of channelosomes and other macromolecular complexes in helping to maintain normal cardiac electrical function, and the defects that prolong the QT interval as a consequence of variants or the effect of drugs. We examine the concept of “interactome mapping” and illustrate by example the multiple protein–protein interactions an ion channel may undergo throughout its lifetime. We also comment on how mapping the interactomes of the different cardiac ion channels may help advance research into LQTS and other cardiac diseases. Finally, we discuss how using human induced pluripotent stem cell technology to model ion channel trafficking and its defects may help accelerate drug discovery toward preventing life-threatening arrhythmias. Advancements in understanding ion channel trafficking and channelosome complexities are needed to find novel therapeutic targets, predict drug interactions, and enhance the overall management and treatment of LQTS patients.
Acute Type A aortic dissection surgical repair in Octogenarians: A meta-analysis
Aortic dissection (AD), a life-threatening condition resulting from aortic wall tears, is especially concerning in the elderly. However, few studies have investigated long-term surgical outcomes in octogenarians with Type A aortic dissection (TAAD). Our paper addresses this critical knowledge gap. Four electronic databases were searched from inception till November 2022 to include any observational or randomized controlled trials (RCT) that evaluate long-term surgical outcomes of TAAD in octogenarians alone or compared with Septuagint focusing on factors including surgical approach, comorbidities, and preoperative status. The Mantel-Haenszel method was used to pool study estimates and calculate odds ratios (OR) with 95% confidence intervals (CI). We included 18,057 participants (10,253 males, 7804 females). In octogenarians and compared to medical treatment, surgical repair achieved significantly lower rates of re-exploration (9%), antegrade cerebral perfusion (33%), stroke (10%), and respiratory failure (19%). In terms of operative data, octogenarians had shorter cardiopulmonary bypass time (161.89 min), cross-clamp time (103.18 min), and myocardial ischemic time (90.89 min). Compared to septuagenarians, octogenarians had significantly shorter cardiopulmonary bypass and systemic cardiac arrest times (−13.84 min and −2.46 min, respectively). Additionally, octogenarians had a higher risk of respiratory complications (RR = 1.60). No significant differences were found for tracheostomy, antegrade cerebral perfusion, neurologic complications, and renal failure. In conclusion, octogenarians undergoing surgical repair for TAAD face relatively lower complication rates, but a higher risk of respiratory issues compared to septuagenarians, emphasizing the unique surgical challenges in this elderly fragile population.
LRP5 promotes adipose progenitor cell fitness and adipocyte insulin sensitivity
WNT signaling plays a key role in postnatal bone formation. Individuals with gain-of-function mutations in the WNT co-receptor LRP5 exhibit increased lower-body fat mass and potentially enhanced glucose metabolism, alongside high bone mass. However, the mechanisms by which LRP5 regulates fat distribution and its effects on systemic metabolism remain unclear. This study aims to explore the role of LRP5 in adipose tissue biology and its impact on metabolism.
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