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Frontiers in Cardiovascular Medicine 2024Abdominal aortic aneurysm (AAA) is a significant source of mortality worldwide and carries a mortality of greater than 80% after rupture. Despite extensive efforts to... (Review)
Review
Abdominal aortic aneurysm (AAA) is a significant source of mortality worldwide and carries a mortality of greater than 80% after rupture. Despite extensive efforts to develop pharmacological treatments, there is currently no effective agent to prevent aneurysm growth and rupture. Current treatment paradigms only rely on the identification and surveillance of small aneurysms, prior to ultimate open surgical or endovascular repair. Recently, regenerative therapies have emerged as promising avenues to address the degenerative changes observed in AAA. This review briefly outlines current clinical management principles, characteristics, and pharmaceutical targets of AAA. Subsequently, a thorough discussion of regenerative approaches is provided. These include cellular approaches (vascular smooth muscle cells, endothelial cells, and mesenchymal stem cells) as well as the delivery of therapeutic molecules, gene therapies, and regenerative biomaterials. Lastly, additional barriers and considerations for clinical translation are provided. In conclusion, regenerative approaches hold significant promise for reversal of tissue damages in AAA, necessitating sustained research and innovation to achieve successful and translatable therapies in a new era in AAA management.
PubMed: 38895536
DOI: 10.3389/fcvm.2024.1369785 -
International Journal of Molecular... May 2024Human abdominal aortic aneurysms (AAAs) are characterized by increased activity of matrix metalloproteinases (MMP), including MMP-12, alongside macrophage accumulation...
Human abdominal aortic aneurysms (AAAs) are characterized by increased activity of matrix metalloproteinases (MMP), including MMP-12, alongside macrophage accumulation and elastin degradation, in conjunction with superimposed atherosclerosis. Previous genetic ablation studies have proposed contradictory roles for MMP-12 in AAA development. In this study, we aimed to elucidate if pharmacological inhibition of MMP-12 activity with a phosphinic peptide inhibitor protects from AAA formation and progression in angiotensin (Ang) II-infused Apoe mice. Complimentary studies were conducted in a human ex vivo model of early aneurysm development. Administration of an MMP-12 inhibitor (RXP470.1) protected hypercholesterolemia Apoe mice from Ang II-induced AAA formation and rupture-related death, associated with diminished medial thinning and elastin fragmentation alongside increased collagen deposition. Proteomic analyses confirmed a beneficial effect of MMP-12 inhibition on extracellular matrix remodeling proteins combined with inflammatory pathways. Furthermore, RXP470.1 treatment of mice with pre-existing AAAs exerted beneficial effects as observed through suppressed aortic dilation and rupture, medial thinning, and elastin destruction. Our findings indicate that pharmacological inhibition of MMP-12 activity retards AAA progression and improves survival in mice providing proof-of-concept evidence to motivate translational work for MMP-12 inhibitor therapy in humans.
Topics: Animals; Aortic Aneurysm, Abdominal; Angiotensin II; Matrix Metalloproteinase 12; Mice; Apolipoproteins E; Humans; Matrix Metalloproteinase Inhibitors; Male; Disease Models, Animal; Mice, Knockout; Mice, Inbred C57BL; Elastin; Proteomics
PubMed: 38891996
DOI: 10.3390/ijms25115809 -
European Journal of Trauma and... Jun 2024Our aim was to update evidence-based and consensus-based recommendations for the surgical and interventional management of blunt or penetrating injuries to the chest in... (Review)
Review
PURPOSE
Our aim was to update evidence-based and consensus-based recommendations for the surgical and interventional management of blunt or penetrating injuries to the chest in patients with multiple and/or severe injuries on the basis of current evidence. This guideline topic is part of the 2022 update of the German Guideline on the Treatment of Patients with Multiple and/or Severe Injuries.
METHODS
MEDLINE and Embase were systematically searched to May and June 2021 respectively for the update and new questions. Further literature reports were obtained from clinical experts. Randomised controlled trials, prospective cohort studies, cross-sectional studies and comparative registry studies were included if they compared interventions for the surgical management of injuries to the chest in patients with multiple and/or severe injuries. We considered patient-relevant clinical outcomes such as mortality, length of stay, and diagnostic test accuracy. Risk of bias was assessed using NICE 2012 checklists. The evidence was synthesised narratively, and expert consensus was used to develop recommendations and determine their strength.
RESULTS
One study was identified. This study compared wedge resection, lobectomy and pneumonectomy in the management of patients with severe chest trauma that required some form of lung resection. Based on the updated evidence and expert consensus, one recommendation was modified and two additional good practice points were developed. All achieved strong consensus. The recommendation on the amount of blood loss that is used as an indication for surgical intervention in patients with chest injuries was modified to reflect new findings in trauma care and patient stabilisation. The new good clinical practice points (GPPs) on the use of video-assisted thoracoscopic surgery (VATS) in patients with initial circulatory stability are also in line with current practice in patient care.
CONCLUSION
As has been shown in recent decades, the treatment of chest trauma has become less and less invasive for the patient as diagnostic and technical possibilities have expanded. Examples include interventional stenting of aortic injuries, video-assisted thoracoscopy and parenchyma-sparing treatment of lung injuries. These less invasive treatment concepts reduce morbidity and mortality in the primary surgical phase following a chest trauma.
PubMed: 38888790
DOI: 10.1007/s00068-024-02556-1 -
European Heart Journal. Case Reports Apr 2024Tyrosine kinase inhibitors targeting the vascular endothelial growth factor (VEGF) inhibitor pathway with immune checkpoint blockade have shown promising outcomes in...
Acute aortic catastrophe caused by cardiovascular oncological manipulation by tyrosine kinase inhibitors with immune checkpoint blockades: a case report and literature review.
BACKGROUND
Tyrosine kinase inhibitors targeting the vascular endothelial growth factor (VEGF) inhibitor pathway with immune checkpoint blockade have shown promising outcomes in managing metastatic renal cancer. However, they increase the risk of a person developing high blood pressure and cardiovascular complications.
CASE SUMMARY
In this study, we report the case of a 73-year-old woman on axitinib and pembrolizumab for her Stage 4 renal cell carcinoma. She presented with intractable chest pain and high systolic blood pressure, not responding to opiates. Her computed tomography angiography results showed an acute intra-mural haematoma with a rupture in the descending thoracic aorta. She underwent emergency thoracic endovascular aortic repair. Post-operatively, she recovered fully without any neurological or cardiovascular issues.
DISCUSSION
The severity of cardiovascular haemodynamic complications arising from the consumption of VEGF inhibitors and from immunotherapy and the lack of anti-hypertensive strategies to adequately manage such events require an unequivocal and urgent assessment of their cardiovascular safety. This case highlights the crucial role of cardiovascular oncology in managing such acute aortic catastrophes.
PubMed: 38887778
DOI: 10.1093/ehjcr/ytae169 -
Journal of Thoracic Disease May 2024Despite improvements in management, infective endocarditis (IE) is still associated with high mortality and morbidity. The outcome of patients with IE remains unclear in...
Postoperative follow-up of 221 patients with infective endocarditis from Gaoligong mountain area of Yunnan in China: a retrospective, single-center, observational cohort study.
BACKGROUND
Despite improvements in management, infective endocarditis (IE) is still associated with high mortality and morbidity. The outcome of patients with IE remains unclear in high-altitude areas of China. To characterize the epidemiological features and surgical outcomes, a retrospective analysis was conducted to 221 patients diagnosed with IE from a single center. In addition, to assess the prognosis of patients, a multivariate logistic regression model was performed to analyze the affecting risk factors.
METHODS
A retrospective analysis was conducted on the clinical data of 221 patients with IE who underwent surgical treatment at the Department of Cardiac Surgery of Yan'an Hospital Affiliated to Kunming Medical University from January 2013 to December 2019. The analysis evaluated patient demographics, pathogenic bacterial composition, echocardiography results, and surgical treatment outcomes. After a 1-year follow-up period, the mortality rate was statistically analyzed. The patients were divided into two groups based on their survival status: those who survived and those who did not. Relevant factors were compared between the two groups, and a multivariate logistic regression model was used to analyze the risk factors that affect the prognosis of patients with IE.
RESULTS
Out of the 221 patients diagnosed with IE, 164 were male and 57 were female, with an average age of 39.25±14.36 years. The most common underlying heart diseases were bicuspid aortic valve disease (24.9%), congenital heart disease (19.5%), rupture of aortic sinus aneurysm (5.0%) and rheumatic valvular disease (2.3%). The blood culture had a positive rate of 48.42% (107/221), with (29.9%) and (13.1%) being the main specifically pathogenic bacteria identified. Transthoracic echocardiography produced positive results in 89.6% (198/221) of cases. The findings included vegetation formation (100%), valve perforation or tear (21.7%), and perivalvular abscess formation (5.6%). Out of the patients, 174 underwent elective surgery, 47 received emergency surgery, and 11 died within 1 year after surgery, resulting in a mortality rate of 5.0%. However, the death group had longer operation time, cardiopulmonary bypass (CPB) time and higher EuroSCORE II compared to the non-death group (P<0.05). Logistic regression analysis identified preoperative hematocrit decrease, prolonged operation time and CPB time, high New York Heart Association (NYHA) cardiac function grade, and liver diseases as risk factors for 1-year mortality in patients with IE (OR =1.003, 0.000, 1.006, 1.026, 1.624 and 4.746).
CONCLUSIONS
IE primarily affects young and middle-aged men with rheumatic heart valvular disease as the main underlying heart disease and as the main pathogen. Surgical intervention significantly reduces early mortality in IE patients. To improve postoperative prognosis, clinicians should remain vigilant, especially in high-risk groups with preoperative hematocrit, prolonged operation time, and CPB time, high NYHA cardiac function grade, EuroSCORE II, and vegetation formation.
PubMed: 38883629
DOI: 10.21037/jtd-24-470 -
Methods in Cell Biology 2024Aortic aneurysms (AAs) are a major public health challenge, featured by a progressive impairs in aortic wall integrity that drives to aortic dilation and, in end stage,...
Aortic aneurysms (AAs) are a major public health challenge, featured by a progressive impairs in aortic wall integrity that drives to aortic dilation and, in end stage, to its rupture. Despite important advances in the surgical treatment of aortic aneurysms, there is currently no pharmacological intervention that prevents their development, reduces their expansion, or avoids their rupture. In addition to classic risk factors such age or gender, several heritable connective tissue disorders have been associated with AA developing, highlighting the role of extracellular matrix (ECM) genes alterations in the developing of AA. In this sense, we have recently demonstrated that global deletion of the cellular communicating network factor 2 (CCN2), previously known as connective tissue growth factor (CTGF) due to its role in the extracellular matrix formation, predisposes to early and lethal AAs development after Angiotensin II (Ang II) infusion in mice. Here, we detail the protocol to induce and detect AAs generation in inducible global CCN2 knockout mice after Ang II infusion which allow the characterization of CCN role in AA development and may help to the development of pharmacological target for AA treatment.
Topics: Animals; Connective Tissue Growth Factor; Mice; Angiotensin II; Mice, Knockout; Aortic Aneurysm; Disease Models, Animal
PubMed: 38880528
DOI: 10.1016/bs.mcb.2024.03.005 -
PloS One 2024Currently, the primary factor indicating the necessity of an operation for an abdominal aortic aneurysm (AAA) is the diameter at its widest part. However, in practice, a...
The role of asymmetry and volume of thrombotic masses in the formation of local deformation of the aneurysmal-altered vascular wall: An in vivo study and mathematical modeling.
Currently, the primary factor indicating the necessity of an operation for an abdominal aortic aneurysm (AAA) is the diameter at its widest part. However, in practice, a large number of aneurysm ruptures occur before reaching a critical size. This means that the mechanics of aneurysm growth and remodeling have not been fully elucidated. This study presents a novel method for assessing the elastic properties of an aneurysm using an ultrasound technique based on tracking the oscillations of the vascular wall as well as the inner border of the thrombus. Twenty nine patients with AAA and eighteen healthy volunteers were considered. The study presents the stratification of a group of patients according to the elastic properties of the aneurysm, depending on the relative volume of intraluminal thrombus masses. Additionally, the neural network analysis of CT angiography images of these patients shows direct (r = 0.664271) correlation with thrombus volume according to ultrasound data, the reliability of the Spearman correlation is p = 0.000215. The use of finite element numerical analysis made it possible to reveal the mechanism of the negative impact on the AAA integrity of an asymmetrically located intraluminal thrombus. The aneurysm itself is considered as a complex structure consisting of a wall, intraluminal thrombus masses, and areas of calcification. When the thrombus occupies > 70% of the lumen of the aneurysm, the deformations of the outer and inner surfaces of the thrombus have different rates, leading to tensile stresses in the thrombus. This poses a risk of its detachment and subsequent thromboembolism or the rupture of the aneurysm wall. This study is the first to provide a mechanistic explanation for the effects of an asymmetrical intraluminal thrombus in an abdominal aortic aneurysm. The obtained results will help develop more accurate risk criteria for AAA rupture using non-invasive conventional diagnostic methods.
Topics: Humans; Aortic Aneurysm, Abdominal; Thrombosis; Male; Female; Aged; Computed Tomography Angiography; Ultrasonography; Middle Aged; Models, Cardiovascular; Aged, 80 and over; Models, Theoretical; Finite Element Analysis
PubMed: 38870116
DOI: 10.1371/journal.pone.0301047 -
European Heart Journal. Case Reports Jun 2024
PubMed: 38863990
DOI: 10.1093/ehjcr/ytae274 -
Vascular Jun 2024Abdominal Aortic Aneurysms (AAA) in females are less prevalent, have higher expansion rates and experience rupture at smaller diameters than in males. Studies have...
OBJECTIVES
Abdominal Aortic Aneurysms (AAA) in females are less prevalent, have higher expansion rates and experience rupture at smaller diameters than in males. Studies have compared outcomes of the retroperitoneal (RP) and transperitoneal (TP) approach in open aortic aneurysm repair (OAR) with conflicting results. No study to date has compared the two approaches solely in females. In this study we compare midterm outcomes of the RP and TP approach in females undergoing OAR.
METHODS
Single-center, retrospective review of all females undergoing OAR from 2010 to 2021. Patients undergoing elective, symptomatic and ruptured OAR were included. The cohort was stratified by surgical approach RP versus TP and midterm outcomes were compared amongst the groups. Outcomes included mortality, graft related, and non-graft related complications.
RESULTS
A total of 244 patients (RP = 133; TP = 111) were identified. Follow-up period was 28 ± 30.7 months. Baseline perioperative characteristics were similar except that more people in the RP group had ejection fraction ((EF) > 50% (82% vs 68%), = .037). Patients who underwent RP repair had longer visceral/renal ischemia time ( = .01), larger graft diameter (18 vs 16 mm; = <0.001), were more likely to have a suprarenal clamp placed(70.5 vs 48.2; < .001), and had decreased autotransfusion volume (611 vs 861 mL; < .01) compared to those who underwent TP repair. Number of deaths was higher in the TP group during study follow-up period (36.4 vs 23.8; = .035), but the difference of the time to event analysis was not significant. There was no difference in all-cause survival at 36 months between RP and TP (77.8 vs 76.8; = .045). Overall midterm complications were 9.5% in both groups. Any graft related complication was 1.8% in TP versus 3% RP ( = .69). In a multivariable model, after adjusting for age, urgency, smoking, prior aneurysm repair, and ASA level, the hazard ratio decreases with the RP approach, however this did not reach significance ( = .052).
CONCLUSION
In a 12-year period of OAR in females, TP and RP results were comparable at midterm analysis. The RP approach appeared to be used more often for OAR requiring suprarenal clamping. Although the TP group had increased mortality, the difference of the time to event analysis was not significant. Midterm postoperative complications in both groups were low. This suggests that both approaches are safe in the female population and decision should be driven by anatomy and surgeon's preference.
PubMed: 38861481
DOI: 10.1177/17085381241257742