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Exploring Integrin α5β1 as a Potential Therapeutic Target for Pulmonary Arterial Hypertension: Insights From Comprehensive Multicenter Preclinical Studies.

Circulation

January 2025

Pulmonary Hypertension Research Group, Québec Heart and Lung Institute Research Center, Quebec City, QC, Canada (S.-E.L., Y.G., T.Y., T.S., M.M., C.R., M.S., S.B.-B., A.B., C.T., A.P., R.E.K., S.M., K.Y., F.P., S.P., O.B., S.B.).

Background: Pulmonary arterial hypertension (PAH) is characterized by obliterative vascular remodeling of the small pulmonary arteries (PAs) and progressive increase in pulmonary vascular resistance leading to right ventricular failure. Although several drugs are approved for the treatment of PAH, mortality rates remain high. Accumulating evidence supports a pathological function of integrins in vessel remodeling, which are gaining renewed interest as drug targets.

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With the advancement in imaging technology, ECG-gated cardiac multidetector computed tomography (MDCT) has emerged as a tool for the anatomic evaluation of the pulmonary valve and right ventricular outflow tract (RVOT) in human medicine. Currently, the evaluation of the pulmonary valve relies primarily on echocardiographic examination. However, the bi-dimensional nature of this technique and the location/orientation of the pulmonary valve in the thoracic cavity can pose challenges.

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Acute esophageal necrosis (AEN) is an uncommon endoscopic finding characterized by a patchy or diffuse circumferential black pigmentation of the esophageal mucosa, corresponding to ischemic necrosis. It usually presents with upper gastrointestinal bleeding and is thought to be caused by a systemic low blood flow in patients with predisposing risk factors, like advanced age and cardiovascular comorbidities. After initial hemodynamic stabilization, diagnosis is established by esophagogastroduodenoscopy (EGD) with careful biopsies and histological evaluation.

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Background And Aims: Porto-sinusoidal vascular disorder (PSVD) is a rare vascular liver disorder characterised by specific histological findings in the absence of cirrhosis, which is poorly understood in terms of pathophysiology. While elevated hepatic copper content serves as diagnostic hallmark in Wilson disease (WD), hepatic copper content has not yet been investigated in PSVD.

Methods: Patients with a verified diagnosis of PSVD at the Medical University of Vienna and available hepatic copper content at the time of diagnosis of PSVD were retrospectively included.

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Tetralogy of Fallot (TOF) is a condition that often leads to long-term enlargement of the aortic root in after surgery. The aortic dilation is believed to be caused by histological abnormalities of the aortic media and the hemodynamic characteristics of increased aortic flow, compared to pulmonary flow. Severe cyanosis, severe right ventricular outflow tract (RVOT) obstruction, older age at repair, a larger aortic size at the time of repair, and a history of an aortopulmonary shunt parameters related to long-standing volume overload of the aortic root were the reported risk factors.

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