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1.
BMC Musculoskelet Disord ; 25(1): 363, 2024 May 07.
Article En | MEDLINE | ID: mdl-38714994

BACKGROUND: Low back pain (LBP) is one of the most common reasons for consultation in general practice. Currently, LBP is categorised into specific and non-specific causes. However, extravertebral causes, such as abdominal aortic aneurysm or pancreatitis, are not being considered. METHODS: A systematic literature search was performed across MEDLINE, Embase, and the Cochrane library, complemented by a handsearch. Studies conducted between 1 January 2001 and 31 December 2020, where LBP was the main symptom, were included. RESULTS: The literature search identified 6040 studies, from which duplicates were removed, leaving 4105 studies for title and abstract screening. Subsequently, 265 publications were selected for inclusion, with an additional 197 publications identified through the handsearch. The majority of the studies were case reports and case series, predominantly originating from specialised care settings. A clear distinction between vertebral or rare causes of LBP was not always possible. A range of diseases were identified as potential extravertebral causes of LBP, encompassing gynaecological, urological, vascular, systemic, and gastrointestinal diseases. Notably, guidelines exhibited inconsistencies in addressing extravertebral causes. DISCUSSION: Prior to this review, there has been no systematic investigation into extravertebral causes of LBP. Although these causes are rare, the absence of robust and reliable epidemiological data hinders a comprehensive understanding, as well as the lack of standardised protocols, which contributes to a lack of accurate description of indicative symptoms. While there are certain disease-specific characteristics, such as non-mechanical or cyclical LBP, and atypical accompanying symptoms like fever, abdominal pain, or leg swelling, that may suggest extravertebral causes, it is important to recognise that these features are not universally present in every patient. CONCLUSION: The differential diagnosis of extravertebral LBP is extensive with relatively low prevalence rates dependent on the clinical setting. Clinicians should maintain a high index of suspicion for extravertebral aetiologies, especially in patients presenting with atypical accompanying symptoms.


Low Back Pain , Humans , Low Back Pain/epidemiology , Low Back Pain/diagnosis , Low Back Pain/etiology , Aortic Aneurysm, Abdominal/epidemiology , Aortic Aneurysm, Abdominal/complications , Pancreatitis/epidemiology , Pancreatitis/diagnosis , Diagnosis, Differential
2.
Medicine (Baltimore) ; 103(19): e38134, 2024 May 10.
Article En | MEDLINE | ID: mdl-38728466

Abdominal aortic aneurysm (AAA) is a dangerous cardiovascular disease, which often brings great psychological burden and economic pressure to patients. If AAA rupture occurs, it is a serious threat to patients' lives. Therefore, it is of clinical value to actively explore the pathogenesis of ruptured AAA and prevent its occurrence. Ferroptosis is a new type of cell death dependent on lipid peroxidation, which plays an important role in many cardiovascular diseases. In this study, we used online data and analysis of ferroptosis-related genes to uncover the formation of ruptured AAA and potential therapeutic targets. We obtained ferroptosis-related differentially expressed genes (Fe-DEGs) from GSE98278 dataset and 259 known ferroptosis-related genes from FerrDb website. Enrichment analysis of differentially expressed genes (DEGs) was performed by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG). Receiver Operating characteristic (ROC) curve was employed to evaluate the diagnostic abilities of Fe-DEGs. Transcription factors and miRNAs of Fe-DEGs were identified through PASTAA and miRDB, miRWalk, TargetScan respectively. Single-sample gene set enrichment analysis (ssGSEA) was used to observe immune infiltration between the stable group and the rupture group. DGIdb database was performed to find potential targeted drugs of DEGs. GO and KEGG enrichment analysis found that DEGs mainly enriched in "cellular divalent inorganic cation homeostasis," "cellular zinc ion homeostasis," "divalent inorganic cation homeostasis," "Mineral absorption," "Cytokine - cytokine receptor interaction," "Coronavirus disease - COVID-19." Two up-regulated Fe-DEGs MT1G and DDIT4 were found to further analysis. Both single and combined applications of MT1G and DDIT4 showed good diagnostic efficacy (AUC = 0.8254, 0.8548, 0.8577, respectively). Transcription factors STAT1 and PU1 of MT1G and ARNT and MAX of DDIT4 were identified. Meanwhile, has_miR-548p-MT1G pairs, has_miR-53-3p/has_miR-181b-5p/ has_miR-664a-3p-DDIT4 pairs were found. B cells, NK cells, Th2 cells were high expression in the rupture group compared with the stable group, while DCs, Th1 cells were low expression in the rupture group. Targeted drugs against immunity, GEMCITABINE and INDOMETHACIN were discovered. We preliminarily explored the clinical significance of Fe-DEGs MT1G and DDIT4 in the diagnosis of ruptured AAA, and proposed possible upstream regulatory transcription factors and miRNAs. In addition, we also analyzed the immune infiltration of stable and rupture groups, and found possible targeted drugs for immunotherapy.


Aortic Aneurysm, Abdominal , Aortic Rupture , Ferroptosis , Ferroptosis/genetics , Humans , Aortic Aneurysm, Abdominal/genetics , Aortic Aneurysm, Abdominal/diagnosis , Aortic Rupture/genetics , MicroRNAs/genetics , Gene Expression Profiling/methods , Gene Ontology , ROC Curve
3.
Int J Mol Sci ; 25(9)2024 May 03.
Article En | MEDLINE | ID: mdl-38732221

Abdominal aortic aneurysm (AAA) has been recognized as a serious chronic inflammatory degenerative aortic disease in recent years. At present, there is no other effective intervention except surgical treatment for AAA. With the aging of the human population, its incidence is increasing year by year, posing a serious threat to human health. Modern studies suggest that vascular chronic inflammatory response is the core process in AAA occurrence and development. Inflammasome, a multiprotein complex located in the cytoplasm, mediates the expression of various inflammatory cytokines like interleukin (IL)-1ß and IL-18, and thus plays a pivotal role in inflammation regulation. Therefore, inflammasome may exert a crucial influence on the progression of AAA. This article reviews some mechanism studies to investigate the role of inflammasome in AAA and then summarizes several potential drugs targeting inflammasome for the treatment of AAA, aiming to provide new ideas for the clinical prevention and treatment of AAA beyond surgical methods.


Aortic Aneurysm, Abdominal , Inflammasomes , Aortic Aneurysm, Abdominal/metabolism , Humans , Inflammasomes/metabolism , Animals , Inflammation/metabolism
4.
Biochim Biophys Acta Mol Basis Dis ; 1870(5): 167224, 2024 Jun.
Article En | MEDLINE | ID: mdl-38723872

BACKGROUND: Pentamethylquercetin (PMQ) is a natural polymethyl flavonoid that possesses anti-apoptotic and other biological properties. Abdominal aortic aneurysm (AAA), a fatal vascular disease with a high risk of rupture, is associated with phenotypic switching and apoptosis of medial vascular smooth muscle cells (VSMCs). This study aimed to investigate the protective effects of PMQ on the development of AAA and the underlying mechanism. METHODS: ApoE-/- mice were continuously infused with angiotensin II (Ang II) for 4 weeks to develop the AAA model. Intragastric administration of PMQ was initiated 5 days before Ang II infusion and continued for 4 weeks. In vitro, VSMCs were cultured and pretreated with PMQ, stimulated with Ang II. Real-time PCR, western blotting, and immunofluorescence staining were used to examine the roles and mechanisms of PMQ on the phenotypic switching and apoptosis of VSMCs. RESULTS: PMQ dose-dependently reduced the incidence of Ang II-induced AAA, aneurysm diameter enlargement, elastin degradation, VSMCs phenotypic switching and apoptosis. Furthermore, PMQ also inhibited phenotypic switching and apoptosis in Ang II-stimulated VSMCs. PMQ exerted protective effects by regulating the C/EBPß/PTEN/AKT/GSK-3ß axis. AAV-mediated overexpression of PTEN reduced the therapeutic effects of PMQ in the AAA model mice, suggesting that the effects of PMQ on Ang II-mediated AAA formation were related to the PTEN/AKT/GSK-3ß axis. PMQ inhibited VSMCs phenotypic switching and apoptosis by bounding to C/EBPß at Lys253 with hydrogen bond to regulate C/EBPß nuclear translocation and PTEN/AKT/GSK-3ß axis, thereby inhibiting Ang II-induced AAA formation. CONCLUSIONS: Pentamethylquercetin inhibits angiotensin II-induced abdominal aortic aneurysm formation by bounding to C/EBPß at Lys253. Therefore, PMQ prevents the formation of AAA and reduces the incidence of AAA.


Angiotensin II , Aortic Aneurysm, Abdominal , Apoptosis , Muscle, Smooth, Vascular , Quercetin , Animals , Aortic Aneurysm, Abdominal/metabolism , Aortic Aneurysm, Abdominal/pathology , Aortic Aneurysm, Abdominal/prevention & control , Aortic Aneurysm, Abdominal/chemically induced , Aortic Aneurysm, Abdominal/drug therapy , Angiotensin II/pharmacology , Mice , Quercetin/analogs & derivatives , Quercetin/pharmacology , Apoptosis/drug effects , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/pathology , Male , Myocytes, Smooth Muscle/metabolism , Myocytes, Smooth Muscle/drug effects , Myocytes, Smooth Muscle/pathology , Disease Models, Animal , PTEN Phosphohydrolase/metabolism , PTEN Phosphohydrolase/genetics , Proto-Oncogene Proteins c-akt/metabolism , Mice, Inbred C57BL , Glycogen Synthase Kinase 3 beta/metabolism , Signal Transduction/drug effects , Cells, Cultured , Cell Nucleus/metabolism , Cell Nucleus/drug effects
5.
Bratisl Lek Listy ; 125(6): 347-353, 2024.
Article En | MEDLINE | ID: mdl-38757590

PURPOSE: Standard endovascular aortic aneurysm repair (EVAR) is sometimes the only treatment option for patients with hostile aortic neck anatomy, but it carries an increased risk of both early and late procedure-related complications. The aim of this study was to report on single-center experience with the Heli-FX EndoAnchors (Medtronic, Santa Rosa, CA) as an adjunctive procedure to endovascular aneurysm repair (EVAR) for prevention and perioperative treatment of proximal neck complications in patients with hostile neck anatomy.  MATERIALS AND METHODS: A single-centre, retrospective study evaluating 24 consecutive patients treated with EndoAnchors during the index EVAR procedure between November 2018 and August 2021. EndoAnchor implantation was indicated for cases with hostile proximal aortic neck anatomy characterised by the presence of at least one of the following parameters: length of 28 mm, angle of >60°, circumferential thrombus/calcification involving ≥50%, and reverse taper. RESULTS:  Median follow-up period was 22.5 months (IQR 2-31.5 months) with no aneurysm-related death, rupture, or conversion to open surgical repair during the follow-up. The procedural success rate was 100%, with no type Ia endoleak at the completion angiography. A mean of 7 EndoAnchors was used per patient (range 4-12). There were no EndoAnchor fractures and dislocations or stent graft fabric damage due to anchor implants. Twenty-three patients (95.8%) remained free of type Ia endoleak and migration on follow-up imaging. Aneurysm sac regression was observed in 13 patients (54.1%), while in 8 patients (33.3%) the sac remained stable. Sac enlargement was present in 1 patient (4.2%) due to late type Ia endoleak. Two patients were lost to the follow-up immediately after the procedure. Between two groups of patients (sac regression versus failure to regress), the larger initial diameter of the proximal neck was the only significant independent factor associated with a lower possibility of sac regression (p= 0,021). CONCLUSIONS:  The use of EndoAnchors during the index EVAR procedure in cases with challenging aortic neck anatomy with or without perioperative type Ia endoleak was associated with good midterm results and led to sac regression in most of the patients (Tab. 4, Fig. 3, Ref. 31).


Aortic Aneurysm, Abdominal , Blood Vessel Prosthesis Implantation , Endovascular Procedures , Humans , Endovascular Procedures/methods , Male , Retrospective Studies , Female , Aged , Aortic Aneurysm, Abdominal/surgery , Aortic Aneurysm, Abdominal/diagnostic imaging , Blood Vessel Prosthesis Implantation/methods , Blood Vessel Prosthesis Implantation/instrumentation , Aged, 80 and over , Postoperative Complications/prevention & control , Endoleak/etiology , Endoleak/prevention & control , Treatment Outcome , Blood Vessel Prosthesis , Stents
6.
Gac Med Mex ; 160(1): 96-103, 2024.
Article En | MEDLINE | ID: mdl-38753543

BACKGROUND: In Mexico, there is a paucity of evidence on mortality and hospitalization patterns associated with aortic aneurysms and dissections. OBJECTIVE: To analyze national databases and describe the epidemiological characteristics of different aortic pathologies. MATERIAL AND METHODS: Retrospective, cross-sectional, observational study, in which mortality and hospitalization attributed to aortic aneurysms and dissections were analyzed. Statistical analysis was performed on Stata 16. RESULTS: A total of 6,049 deaths were documented in the general population, which included 2,367 hospitalizations and 476 (20.1%) in-hospital deaths. In addition, a statistically significant age difference was found between mean age at death in the general population (69.5 years) and the in-hospital death group (64.1 years, p < 0.001). As for hospitalizations secondary to ruptured abdominal aortic aneurysms, 149 cases were identified, with a mean age of 65.6 years, out of whom 53 (35.5%) were under 65 years of age, with a mean age of 47.8 years. CONCLUSIONS: Epidemiological reports of aortic pathology in Mexico are scarce; therefore, implementation of screening and detection programs for aortic pathologies is necessary in order to address the disparities identified in this analysis.


ANTECEDENTES: Existe evidencia escasa en México respecto a la mortalidad y patrones del ingreso hospitalario asociados a aneurismas y disecciones aórticos. OBJETIVO: Analizar las bases de datos nacionales y describir las características epidemiológicas de diferentes patologías aórticas agudas. MATERIAL Y MÉTODOS: Estudio transversal y observacional de una base de datos retrospectiva, en el que se analizó la mortalidad y hospitalización atribuidas a aneurismas y disecciones aórticos. El análisis estadístico se realizó en Stata 16. RESULTADOS: Se documentaron 6049 muertes en la población general, 2367 hospitalizaciones y 476 muertes intrahospitalarias. Adicionalmente, se encontró una diferencia estadísticamente significativa entre las medias de edad de fallecimiento de la población general (65.5 años) y de los pacientes que murieron en el hospital (64.1 años), p < 0.001. En cuanto a las hospitalizaciones secundarias a aneurisma de aorta abdominal roto, 149 casos fueron evidenciados con una media de edad de 65.6 años; 53 (35.5 %) de estos tenía menos de 65 años, con una media de edad de 47.8 años. CONCLUSIONES: Los reportes epidemiológicos de patología aórtica en México son escasos, por ello la implementación de programas de tamizaje y la detección de patologías aórticas son necesarias para mejorar las disparidades encontradas en este análisis.


Aortic Aneurysm , Aortic Dissection , Hospital Mortality , Hospitalization , Humans , Mexico/epidemiology , Middle Aged , Aortic Dissection/epidemiology , Aortic Dissection/mortality , Male , Cross-Sectional Studies , Female , Retrospective Studies , Aged , Aortic Aneurysm/epidemiology , Aortic Aneurysm/mortality , Hospitalization/statistics & numerical data , Hospitalization/trends , Adult , Hospital Mortality/trends , Aged, 80 and over , Aortic Aneurysm, Abdominal/epidemiology , Aortic Aneurysm, Abdominal/mortality , Young Adult , Adolescent
7.
J Cardiothorac Surg ; 19(1): 276, 2024 May 04.
Article En | MEDLINE | ID: mdl-38704597

BACKGROUND: Conventional graft replacement for a juxtarenal abdominal aortic aneurysm (JRAAA) remains challenging for high-risk patients since it often requires the reconstruction of some visceral arteries. CASE PRESENTATION: A 76-year-old woman was diagnosed with an 87 × 48 mm saccular JRAAA. Open graft replacement was contraindicated because of frailty and a past history of trans-thoracoabdominal esophagectomy. Chimney endovascular aortic repair (ChEVAR) with three chimney endografts was successfully performed without any endoleaks, and each visceral circulation was kept intact. The patient was discharged uneventfully on postoperative day 8. Significant shrinkage of the aneurysmal sac and preservation of flow through each chimney graft were observed on computed tomography 6 months postoperatively, with no significant increase in serum creatinine levels on laboratory testing. CONCLUSIONS: ChEVAR can be a useful surgical option instead of conventional operations, especially for high-risk cases.


Aortic Aneurysm, Abdominal , Blood Vessel Prosthesis Implantation , Endovascular Procedures , Esophagectomy , Humans , Female , Aged , Aortic Aneurysm, Abdominal/surgery , Endovascular Procedures/methods , Esophagectomy/adverse effects , Esophagectomy/methods , Blood Vessel Prosthesis Implantation/methods , Tomography, X-Ray Computed , Endovascular Aneurysm Repair
8.
Ugeskr Laeger ; 186(17)2024 Apr 22.
Article Da | MEDLINE | ID: mdl-38704706

A focused point-of-care abdominal ultrasound is an examination performed at the patient's location and interpreted within the clinical context. This review gives an overview of this examination modality. The objective is to rapidly address predefined dichotomised questions about the presence of an abdominal aortic aneurysm, gallstones, cholecystitis, hydronephrosis, urinary retention, free intraperitoneal fluid, and small bowel obstruction. FAUS is a valuable tool for emergency physicians to promptly confirm various conditions upon the patients' arrival, thus reducing the time to diagnosis and in some cases eliminating the need for other imaging.


Aortic Aneurysm, Abdominal , Hydronephrosis , Ultrasonography , Humans , Ultrasonography/methods , Aortic Aneurysm, Abdominal/diagnostic imaging , Hydronephrosis/diagnostic imaging , Abdomen/diagnostic imaging , Gallstones/diagnostic imaging , Cholecystitis/diagnostic imaging , Intestinal Obstruction/diagnostic imaging , Urinary Retention/diagnostic imaging , Urinary Retention/etiology , Point-of-Care Systems
9.
Zhonghua Nei Ke Za Zhi ; 63(5): 468-473, 2024 May 01.
Article Zh | MEDLINE | ID: mdl-38715483

Objective: To examine the perioperative clinical features and prognosis of patients with ruptured abdominal aortic aneurysms (rAAA) who received surgical repair. Methods: The clinical data of rAAA patients who underwent surgical repair and were admitted to the Surgical Intensive Care Unit of Beijing Anzhen Hospital, Capital Medical University from August 2005 to November 2020 were retrospectively analyzed, including the general clinical features, surgical mode, intraoperative conditions, postoperative complications, and fatality rate. Results: There were 117 patients with rAAA, with a median age of 68 (62,77) years, including 93 men (79.5%) and 24 women (20.5%). The main clinical manifestation was abdominal pain (n=115, 98.3%). Among them, 65 (55.6%) patients underwent endovascular aneurysm repair (EVAR), while 52 (44.4%) underwent open surgical repair (OSR). The common postoperative complications include acute gastrointestinal dysfunction (n=116, 99.1%), shock (n=89, 76.1%), acute respiratory distress syndrome (n=85, 72.6%), pancreatic injury (n=56, 47.9%), coagulation dysfunction (n=55, 47.0%), disseminated intravascular coagulation (n=46, 39.3%), acute kidney injury (n=39, 33.3%), infection/sepsis (n=28, 23.9%), gastrointestinal bleeding (n=17, 14.5%), and abdominal compartment syndrome (n=12, 10.3%). The overall postoperative in-hospital fatality rate was 10.3% (12/117). Preoperative use of vasopressors and inotropes, retroperitoneal hematoma, and postoperative abdominal compartment syndrome, gastrointestinal hemorrhage, acute kidney injury, and diffuse intravascular coagulation significantly increased the fatality rate [5/11, 6/24, 5/16, 6/12, 6/17, 23.1%(9/39), 19.6%(9/46), respectively]. Conclusion: The postoperative mortality of rAAA patients is still high in the era of EVAR, especially in patients with preoperative existence of shock and retroperitoneal hematoma, and with postoperative abdominal compartment syndrome, coagulation dysfunction, and acute kidney injury. It is necessary to strengthen perioperative monitoring and management of these patients to reduce the fatality rate.


Aortic Aneurysm, Abdominal , Aortic Rupture , Postoperative Complications , Humans , Female , Male , Aortic Aneurysm, Abdominal/surgery , Aged , Retrospective Studies , Middle Aged , Postoperative Complications/epidemiology , Aortic Rupture/surgery , Prognosis , Endovascular Procedures , Data Analysis
11.
Sci Transl Med ; 16(745): eadh1763, 2024 May.
Article En | MEDLINE | ID: mdl-38691618

An abdominal aortic aneurysm (AAA) is a life-threatening cardiovascular disease. We identified plasma insulin-like growth factor 1 (IGF1) as an independent risk factor in patients with AAA by correlating plasma IGF1 with risk. Smooth muscle cell- or fibroblast-specific knockout of Igf1r, the gene encoding the IGF1 receptor (IGF1R), attenuated AAA formation in two mouse models of AAA induced by angiotensin II infusion or CaCl2 treatment. IGF1R was activated in aortic aneurysm samples from human patients and mice with AAA. Systemic administration of IGF1C, a peptide fragment of IGF1, 2 weeks after disease development inhibited AAA progression in mice. Decreased AAA formation was linked to competitive inhibition of IGF1 binding to its receptor by IGF1C and modulation of downstream alpha serine/threonine protein kinase (AKT)/mammalian target of rapamycin signaling. Localized application of an IGF1C-loaded hydrogel was developed to reduce the side effects observed after systemic administration of IGF1C or IGF1R antagonists in the CaCl2-induced AAA mouse model. The inhibitory effect of the IGF1C-loaded hydrogel administered at disease onset on AAA formation was further evaluated in a guinea pig-to-rat xenograft model and in a sheep-to-minipig xenograft model of AAA formation. The therapeutic efficacy of IGF1C for treating AAA was tested through extravascular delivery in the sheep-to-minipig model with AAA established for 2 weeks. Percutaneous injection of the IGF1C-loaded hydrogel around the AAA resulted in improved vessel flow dynamics in the minipig aorta. These findings suggest that extravascular administration of IGF1R antagonists may have translational potential for treating AAA.


Aortic Aneurysm, Abdominal , Disease Models, Animal , Insulin-Like Growth Factor I , Receptor, IGF Type 1 , Animals , Receptor, IGF Type 1/metabolism , Receptor, IGF Type 1/antagonists & inhibitors , Humans , Aortic Aneurysm, Abdominal/pathology , Aortic Aneurysm, Abdominal/drug therapy , Aortic Aneurysm, Abdominal/metabolism , Aortic Aneurysm, Abdominal/prevention & control , Insulin-Like Growth Factor I/metabolism , Male , Swine , Mice , Signal Transduction/drug effects , Mice, Inbred C57BL , Rats
13.
BMJ Open ; 14(4): e081046, 2024 Apr 16.
Article En | MEDLINE | ID: mdl-38626979

INTRODUCTION: Incisional hernia (IH) is a prevalent and potentially dangerous complication of abdominal surgery, especially in high-risk groups. Mesh reinforcement of the abdominal wall has been studied as a potential intervention to prevent IHs. Randomised controlled trials (RCTs) have demonstrated that prophylactic mesh reinforcement after abdominal surgery, in general, is effective and safe. In patients with abdominal aortic aneurysm (AAA), prophylactic mesh reinforcement after open repair has not yet been recommended in official guidelines, because of relatively small sample sizes in individual trials. Furthermore, the identification of subgroups that benefit most from prophylactic mesh placement requires larger patient numbers. Our primary aim is to evaluate the efficacy and effectiveness of the use of a prophylactic mesh after open AAA surgery to prevent IH by performing an individual patient data meta-analysis (IPDMA). Secondary aims include the evaluation of postoperative complications, pain and quality of life, and the identification of potential subgroups that benefit most from prophylactic mesh reinforcement. METHODS AND ANALYSIS: We will conduct a systematic review to identify RCTs that study prophylactic mesh placement after open AAA surgery. Cochrane Central Register of Controlled Trials, MEDLINE Ovid, Embase, Web of Science Core Collection and Google Scholar will be searched from the date of inception onwards. RCTs must directly compare primary sutured closure with mesh closure in adult patients who undergo open AAA surgery. Lead authors of eligible studies will be asked to share individual participant data (IPD). The risk of bias (ROB) for each included study will be assessed using the Cochrane ROB tool. An IPDMA will be performed to evaluate the efficacy, with the IH rate as the primary outcome. Any signs of heterogeneity will be evaluated by Forest plots. Time-to-event analyses are performed using Cox regression analysis to evaluate risk factors. ETHICS AND DISSEMINATION: No new data will be collected in this study. We will adhere to institutional, national and international regulations regarding the secure and confidential sharing of IPD, addressing ethics as indicated. We will disseminate findings via international conferences, open-source publications in peer-reviewed journals and summaries posted online. PROSPERO REGISTRATION NUMBER: CRD42022347881.


Aortic Aneurysm, Abdominal , Incisional Hernia , Adult , Humans , Incisional Hernia/prevention & control , Incisional Hernia/surgery , Surgical Mesh , Postoperative Complications/etiology , Laparotomy/adverse effects , Aortic Aneurysm, Abdominal/surgery , Systematic Reviews as Topic , Meta-Analysis as Topic
14.
Int J Biol Sci ; 20(6): 2092-2110, 2024.
Article En | MEDLINE | ID: mdl-38617538

Development of non-surgical treatment of human abdominal aortic aneurysm (AAA) has clinical significance. Colchicine emerges as an effective therapeutic regimen in cardiovascular diseases. Yet, whether colchicine slows AAA growth remain controversy. Here, we demonstrated that daily intragastric administration of low-dose colchicine blocked AAA formation, prevented vascular smooth muscle cell (SMC) phenotype switching and apoptosis, and vascular inflammation in both peri-aortic CaPO4 injury and subcutaneous angiotensin-II infusion induced experimental AAA mice models. Mechanistically, colchicine increased global mRNA stability by inhibiting the METTL14/YTHDC1-mediated m6A modification, resulting in increased sclerostin (SOST) expression and consequent inactivation of the WNT/ß-catenin signaling pathway in vascular SMCs from mouse AAA lesions and in cultured human aortic SMCs. Moreover, human and mouse AAA lesions all showed increased m6A methylation, decreased SOST expression, and skewed synthetic SMC de-differentiation phenotype, compared to those without AAA. This study uncovers a novel mechanism of colchicine in slowing AAA development by using the METTL14/SOST/WNT/ß-catenin axis to control vascular SMC homeostasis in mouse aortic vessels and in human aortic SMCs. Therefore, use of colchicine may benefit AAA patients in clinical practice.


Aortic Aneurysm, Abdominal , Muscle, Smooth, Vascular , Humans , Animals , Mice , Aortic Aneurysm, Abdominal/drug therapy , Homeostasis , Aorta , Colchicine/therapeutic use
16.
J R Soc Interface ; 21(213): 20230656, 2024 Apr.
Article En | MEDLINE | ID: mdl-38593843

Peripheral arterial disease (PAD) and abdominal aortic aneurysms (AAAs) often coexist and pose significant risks of mortality, yet their mutual interactions remain largely unexplored. Here, we introduce a fluid mechanics model designed to simulate the haemodynamic impact of PAD on AAA-associated risk factors. Our focus lies on quantifying the uncertainty inherent in controlling the flow rates within PAD-affected vessels and predicting AAA risk factors derived from wall shear stress. We perform a sensitivity analysis on nine critical model parameters through simulations of three-dimensional blood flow within a comprehensive arterial geometry. Our results show effective control of the flow rates using two-element Windkessel models, although specific outlets need attention. Quantities of interest like endothelial cell activation potential (ECAP) and relative residence time are instructive for identifying high-risk regions, with ECAP showing greater reliability and adaptability. Our analysis reveals that the uncertainty in the quantities of interest is 187% of that of the input parameters. Notably, parameters governing the amplitude and frequency of the inlet velocity exert the strongest influence on the risk factors' variability and warrant precise determination. This study forms the foundation for patient-specific simulations involving PAD and AAAs which should ultimately improve patient outcomes and reduce associated mortality rates.


Aortic Aneurysm, Abdominal , Peripheral Arterial Disease , Humans , Reproducibility of Results , Uncertainty , Models, Cardiovascular , Hemodynamics , Stress, Mechanical
17.
Cell Mol Life Sci ; 81(1): 175, 2024 Apr 10.
Article En | MEDLINE | ID: mdl-38597937

Phenotypic transformation of vascular smooth muscle cells (VSMCs) plays a crucial role in abdominal aortic aneurysm (AAA) formation. CARMN, a highly conserved, VSMC-enriched long noncoding RNA (lncRNA), is integral in orchestrating various vascular pathologies by modulating the phenotypic dynamics of VSMCs. The influence of CARMN on AAA formation, particularly its mechanisms, remains enigmatic. Our research, employing single-cell and bulk RNA sequencing, has uncovered a significant suppression of CARMN in AAA specimens, which correlates strongly with the contractile function of VSMCs. This reduced expression of CARMN was consistent in both 7- and 14-day porcine pancreatic elastase (PPE)-induced mouse models of AAA and in human clinical cases. Functional analyses disclosed that the diminution of CARMN exacerbated PPE-precipitated AAA formation, whereas its augmentation conferred protection against such formation. Mechanistically, we found CARMN's capacity to bind with SRF, thereby amplifying its role in driving the transcription of VSMC marker genes. In addition, our findings indicate an enhancement in CAMRN transcription, facilitated by the binding of NRF2 to its promoter region. Our study indicated that CARMN plays a protective role in preventing AAA formation and restrains the phenotypic transformation of VSMC through its interaction with SRF. Additionally, we observed that the expression of CARMN is augmented by NRF2 binding to its promoter region. These findings suggest the potential of CARMN as a viable therapeutic target in the treatment of AAA.


Aortic Aneurysm, Abdominal , RNA, Long Noncoding , Humans , Mice , Animals , Swine , RNA, Long Noncoding/genetics , Muscle, Smooth, Vascular , NF-E2-Related Factor 2/genetics , Aortic Aneurysm, Abdominal/chemically induced , Aortic Aneurysm, Abdominal/genetics , Disease Models, Animal
18.
J Cardiovasc Surg (Torino) ; 65(2): 85-98, 2024 Apr.
Article En | MEDLINE | ID: mdl-38635284

Endovascular aortic repair (EVAR) is nowadays the establishment treatment for patients with abdominal aortic aneurysm (AAA) both in elective and urgent setting. Despite the large applicability and satisfactory results, the presence of hostile iliac anatomy affects both technical and clinical success. This narrative review aimed to report the impact of iliac access and related adjunctive procedures in patients undergoing EVAR in elective and non-elective setting. Hostile iliac access can be defined in presence of narrowed, tortuous, calcified, or occluded iliac arteries. These iliac characteristics can be graded by the anatomic severity grade score to quantitatively assess anatomic complexity before undergoing treatment. Literature shows that iliac hostility has an impact on device navigability, insertion and perioperative and postoperative results. Overall, it has been correlated to higher rate of access issues, representing up to 30% of the first published EVAR experience. Recent innovations with low-profile endografts have reduced large-bore sheaths related issues. However, iliac-related complications still represent an issue, and several adjunctive endovascular and surgical strategies are nowadays available to overcome these complications during EVAR. In urgent settings iliac hostility can significantly impact on particular time sensitive procedures. Moreover, in case of severe hostility patients might be written off for EVAR repair might be inapplicable, exposing to higher mortality/morbidity risk in this urgent/emergent setting. In conclusion, an accurate anatomical evaluation of iliac arteries during preoperative planning, materials availability, and skilled preparation to face iliac-related issues are crucial to address these challenges.


Aortic Aneurysm, Abdominal , Blood Vessel Prosthesis Implantation , Elective Surgical Procedures , Endovascular Procedures , Iliac Artery , Humans , Aortic Aneurysm, Abdominal/surgery , Aortic Aneurysm, Abdominal/diagnostic imaging , Endovascular Procedures/adverse effects , Endovascular Procedures/instrumentation , Iliac Artery/surgery , Iliac Artery/diagnostic imaging , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis Implantation/instrumentation , Treatment Outcome , Risk Factors , Blood Vessel Prosthesis , Postoperative Complications/etiology
19.
J Cardiovasc Surg (Torino) ; 65(2): 124-131, 2024 Apr.
Article En | MEDLINE | ID: mdl-38635285

INTRODUCTION: We performed a systematic review and meta-analysis to assess the existing published evidence regarding the safety and efficacy of the endovascular aortic repair with chimney technique (ch-EVAR) and physician-modified stent-grafts (PMSGs) for the treatment of pararenal aortic aneurysm repair. EVIDENCE ACQUISITION: A systematic search of all relevant studies reported until October 2023 according to the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines was performed. The pooled 30-day mortality, peri- and postoperative complication rates were estimated using fixed or random effect methods. EVIDENCE SYNTHESIS: A total of 679 study titles were identified by the initial search strategy, of which 16 were considered eligible for inclusion in the meta-analysis. A total of 1094 patients (ch-EVAR N.=861 and PMSG N.=233) (90% male) were identified. The pooled 30-day mortality rate was 3.4% for ch-EVAR and 2.6% for PMSG. The major adverse events (MAE) in the early period was 14.7% for ch-EVAR and 18.5% PMSG, respectively. Higher occlusion rate was observed of the chimney stents grafts (8.2%) than the bridging stents (1.4%) during the follow-up period. CONCLUSIONS: Ch-EVAR and physician-modified technology are safe with low 30-day mortality in elective settings for pararenal aortic aneurysms repair. No significant differences were seen between the two surgical methods regarding the early major adverse events rate. However, higher occlusion rate for the chimneys can be expected over time.


Aortic Aneurysm, Abdominal , Blood Vessel Prosthesis Implantation , Blood Vessel Prosthesis , Endovascular Procedures , Postoperative Complications , Prosthesis Design , Stents , Humans , Endovascular Procedures/adverse effects , Endovascular Procedures/instrumentation , Endovascular Procedures/mortality , Endovascular Procedures/methods , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis Implantation/instrumentation , Blood Vessel Prosthesis Implantation/mortality , Treatment Outcome , Aortic Aneurysm, Abdominal/surgery , Aortic Aneurysm, Abdominal/mortality , Aortic Aneurysm, Abdominal/diagnostic imaging , Postoperative Complications/etiology , Risk Factors , Male , Female , Aged , Time Factors , Risk Assessment , Middle Aged
20.
J Cardiovasc Surg (Torino) ; 65(2): 110-118, 2024 Apr.
Article En | MEDLINE | ID: mdl-38635286

BACKGROUND: The aim of this study was to evaluate the anatomical feasibility of current available fenestrated endografts (FEVAR) and on-label chimney technique (EnChEVAR) in patients with complex abdominal aortic aneurysms (C-AAA). METHODS: Feasibility of EnChEVAR (Endurant II/IIS CE-marked [Medtronic]) and 4 types of FEVAR (Zenith Fenestrated CE-marked, Zenith Fenestrated Low-Profile [LP] custom-made device [CMD] [Cook Medical], Fenestrated Anaconda LoPro90 CMD, Fenestrated Treo CMD [Terumo Aortic]) was assessed according to the manufacturer's instructions for use. Computed tomography angiograms of patients with C-AAA previously included in the Protagoras 2.0 study were retrospectively reviewed. The aortic coverage was ideally planned to involve a maximum of two chimney grafts or fenestrations. RESULTS: Iliac access and aortic neck of 73 C-AAAs were analyzed. The overall feasibility was significantly different between EnChEVAR (33%) and FEVAR (Zenith Fenestrated 15%, Zenith Fenestrated LP 15%, Fenestrated Anaconda LoPro90 45%, Fenestrated Treo 48%). The iliac access feasibility was significantly lower for Zenith Fenestrated with standard profile compared to all other grafts. The aortic neck feasibility was significantly higher for EnChEVAR and both Terumo Aortic fenestrated stent grafts, compared to both Cook Medical grafts. The treatment using any of the three current available fenestrated grafts with lower profile (Zenith Fenestrated LP, Fenestrated Anaconda LoPro90, Fenestrated Treo) would have been feasible in 71% of the cases. CONCLUSIONS: Most of the patients treated by ChEVAR would have not been treated by first generation fenestrated stent graft. The current available fenestrated endografts, with lower profile and suitable also for angulated necks, increase the anatomical feasibility.


Aortic Aneurysm, Abdominal , Blood Vessel Prosthesis Implantation , Blood Vessel Prosthesis , Computed Tomography Angiography , Endovascular Procedures , Feasibility Studies , Prosthesis Design , Stents , Humans , Aortic Aneurysm, Abdominal/surgery , Aortic Aneurysm, Abdominal/diagnostic imaging , Endovascular Procedures/instrumentation , Endovascular Procedures/adverse effects , Blood Vessel Prosthesis Implantation/instrumentation , Blood Vessel Prosthesis Implantation/adverse effects , Retrospective Studies , Female , Male , Aged , Treatment Outcome , Aged, 80 and over , Contrast Media , Aortography
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