Angiopoietin-2 predicts morbidity in adults with Fontan physiology.

Morbidity in patients with single-ventricle Fontan circulation is common and includes arrhythmias, edema, and pulmonary arteriovenous malformations (PAVM) among others. We sought to identify biomarkers that may predict such complications. Twenty-five patients with Fontan physiology and 12 control patients with atrial septal defects (ASD) that underwent cardiac catheterization were included. Plasma was collected from the hepatic vein and superior vena cava and underwent protein profiling for a panel of 20 analytes involved in angiogenesis and endothelial dysfunction. Ten (40%) of Fontan patients had evidence of PAVM, eighteen (72%) had a history of arrhythmia, and five (20%) were actively in arrhythmia or had a recent arrhythmia. Angiopoietin-2 (Ang-2) was higher in Fontan patients (8,875.4 ± 3,336.9 pg/mL) versus the ASD group (1,663.6 ± 587.3 pg/mL, p < 0.0001). Ang-2 was higher in Fontan patients with active or recent arrhythmia (11,396.0 ± 3,457.7 vs 8,118.2 ± 2,795.1 pg/mL, p < 0.05). A threshold of 8,500 pg/mL gives Ang-2 a negative predictive value of 100% and positive predictive value of 42% in diagnosing recent arrhythmia. Ang-2 is elevated among adults with Fontan physiology. Ang-2 level is associated with active or recent arrhythmia, but was not found to be associated with PAVM

Predictors of postoperative complications following thyroidectomy: A systematic review

Introduction: Thyroidectomy is considered a relatively safe procedure with a low risk of postoperative complications, making it challenging to identify predictors of complications to improve shared decision making. Recent advancements in clinical bioinformatics and surgical decision-making tools have the potential to improve patient outcomes. This systematic review aimed to assess the current understanding of factors predicting such complications following thyroidectomy. Methods: We searched PubMed/MEDLINE, Web of Science, and EMBASE for studies published between 2010 and October 2023, investigating predictors of postoperative complications after thyroidectomy. Studies were included if they investigated predictors of hypocalcemia, hypoparathyroidism, vocal cord paresis (VCP), hematoma, or other postoperative complications. Studies solely reliant on univariate and ROC analyses were excluded. Independent predictors of each postoperative complication were evaluated and categorized as biochemical, surgical, and patient/disease specific. Results: Forty-five studies were included. Biochemical hypocalcemia and transient hypoparathyroidism were the most investigated complications, with reported rates ranging from 15.7 % to 76.7 % and 12.9 % to 53.8 %, respectively. The majority of studies (n = 35, 77 %) focused on these complications. Biochemical markers (e.g., serum calcium, parathyroid hormone) were the most frequent predictors identified for these complications. Surgical factors (inadvertent parathyroidectomy) were frequently studied for all complications. Age, gender, and thyroid pathology were common patient/disease-specific predictors. Conclusion: This review highlights the disparity in research on complication predictors. Most studies focused on hypocalcemia and hypoparathyroidism, with fewer examining VCP, hematoma, and mortality. Notably, a lack of high-quality evidence exists due to the scarcity of prospective and randomized controlled trials. Future research should explore incorporating a wider range of independent predictors, especially surgical factors, into comprehensive predictive models. This review can serve as a foundation for developing such models to improve risk prediction for a broader spectrum of thyroidectomy complications

Reproducible Arterial Denudation Injury by Infrarenal Abdominal Aortic Clamping in a Murine Model.

Percutaneous vascular interventions uniformly result in arterial denudation injuries that subsequently lead to thrombosis and restenosis. These complications can be attributed to impairments in re-endothelialization within the wound margins. Yet, the cellular and molecular mechanisms of re-endothelialization remain to be defined. While several animal models to study re-endothelialization after arterial denudation are available, few are performed in the mouse because of surgical limitations. This undermines the opportunity to exploit transgenic mouse lines and investigate the contribution of specific genes to the process of re-endothelialization. Here, we present a step-by-step protocol for creating a highly reproducible murine model of arterial denudation injury in the infrarenal abdominal aorta using external vascular clamping. Immunocytochemical staining of injured aortas for fibrinogen and β-catenin demonstrate the exposure of a pro-thrombotic surface and the border of intact endothelium, respectively. The method presented here has the advantages of speed, excellent overall survival rate, and relative technical ease, creating a uniquely practical tool for imposing arterial denudation injury in transgenic mouse models. Using this method, investigators may elucidate the mechanisms of re-endothelialization under normal or pathological conditions

A multi-step transcriptional cascade underlies vascular regeneration in vivo.

The molecular mechanisms underlying vascular regeneration and repair are largely unknown. To gain insight into this process, we developed a method of intima denudation, characterized the progression of endothelial healing, and performed transcriptome analysis over time. Next-generation RNA sequencing (RNAseq) provided a quantitative and unbiased gene expression profile during in vivo regeneration following denudation injury. Our data indicate that shortly after injury, cells immediately adjacent to the wound mount a robust and rapid response with upregulation of genes like Jun, Fos, Myc, as well as cell adhesion genes. This was quickly followed by a wave of proliferative genes. After completion of endothelial healing a vigorous array of extracellular matrix transcripts were upregulated. Gene ontology enrichment and protein network analysis were used to identify transcriptional profiles over time. Further data mining revealed four distinct stages of regeneration: shock, proliferation, acclimation, and maturation. The transcriptional signature of those stages provides insight into the regenerative machinery responsible for arterial repair under normal physiologic conditions

Endothelial Regeneration of Large Vessels Is a Biphasic Process Driven by Local Cells with Distinct Proliferative Capacities.

The cellular and mechanistic bases underlying endothelial regeneration of adult large vessels have proven challenging to study. Using a reproducible in vivo aortic endothelial injury model, we characterized cellular dynamics underlying the regenerative process through a combination of multi-color lineage tracing, parabiosis, and single-cell transcriptomics. We found that regeneration is a biphasic process driven by distinct populations arising from differentiated endothelial cells. The majority of cells immediately adjacent to the injury site re-enter the cell cycle during the initial damage response, with a second phase driven by a highly proliferative subpopulation. Endothelial regeneration requires activation of stress response genes including Atf3, and aged aortas compromised in their reparative capacity express less Atf3. Deletion of Atf3 reduced endothelial proliferation and compromised the regeneration. These findings provide important insights into cellular dynamics and mechanisms that drive responses to large vessel injury