Enhancing postoperative pain control by surgically-initiated rectus sheath block in abdominal aortic aneurysm open repair: A case report

BACKGROUND Abdominal aortic aneurysm(AAA)repair often involves significant postoperative pain,traditionally managed with systemic opioids,which can cause undesirable side effects.This case report explores the novel use of a surgically-initiated rectus sheath block with a catheter-over-needle assembly for pain management in AAA repair.CASE SUMMARY A 67-year-old female with hypertension and previous aortic dissection underwent elective open repair of an infrarenal AAA,which had grown from 3.4 cm to 4.3 cm over 14 months.A rectus sheath block was initiated surgically for postoperative pain control.The patient reported low pain scores and did not require systemic intravenous opioids,enabling early ambulation and discharge on postoperative day seven without complications.By preventing complications of systemic opi-oids,the method indicating a promising direction for postoperative pain management in major vascular surgeries.CONCLUSION Surgically-initiated rectus sheath block as a valuable tool for managing postoperative pain in AAA repair.

The incidence rate and histological characteristics of intimal hyperplasia in elastase-induced experimental abdominal aortic aneurysms in mice

Intimal hyperplasia(IH)is a negative vascular remodeling after arterial injury.IH occasionally occurs in elastase-induced abdominal aortic aneurysm(AAA)mouse models.This study aims to clarify the incidence and histological characteristics of IH in aneurysmal mice.A retrospective study was conducted by including 42 male elastaseinduced mouse AAA models.The IH incidence,aortic diameters with or without IH,and hyperplasia lesional features of mice were analyzed.Among 42 elastase-induced AAA mouse models,10 mice developed mild IH(24%)and severe IH was found in only 2 mice(5%).The outer diameters of the AAA segments in mice with and without IH did not show significant difference.Both mild and severe IH lesions show strong smooth muscle cell positive staining,but endothelial cells were occasionally observed in severe IH lesions.There was obvious macrophage infiltration in the IH lesions of the AAA mouse models,especially in mice with severe IH.However,only a lower numbers of T cells and B cells were found in the IH lesion.Local cell-secreted matrix metalloproteinases(MMP)2 was highly expressed in all IH lesions,but MMP9 was only overexpressed in severe lesions.In conclusion,this study is the first to demonstrate the occurrence of aneurysmal IH and its histological characteristics in an elastaseinduced mouse AAA model.This will help researchers better understand this model,and optimize it for use in AAA-related research.

Causal Relationship between Chronic Obstructive Pulmonary Disease and Abdominal Aortic Aneurysm: A Mendelian Randomization Study

Background: Chronic Obstructive Pulmonary Disease (COPD) is a chronic inflammatory lung condition associated with significant morbidity and mortality. Observational studies indicate a positive correlation between COPD and the risk of abdominal aortic aneurysm (AAA), suggesting individuals with COPD are more likely to develop AAA. However, the causal relationship between COPD and AAA remains unclear. Method: This study employed a bidirectional Mendelian Randomization (MR) approach to assess the causal relationship between COPD and AAA. A two-step MR analysis was conducted to evaluate the mediating effect of 1400 circulating metabolites between COPD and AAA. Expression quantitative trait loci (eQTL) were sourced from the MRC Integrative Epidemiology Unit (MRC-IEU) database, and MR analysis was performed using the TwoSampleMR R package. The results were filtered using the Inverse Variance Weighted (IVW) method to identify genes strongly associated with both COPD and AAA. Furthermore, the Super Exact Test R package was utilized to determine the overlapping genes between COPD and AAA. Enrichment analysis for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was conducted using the clusterProfiler R package. Protein-protein interaction (PPI) analysis was carried out using STRING v12.0. Results: The IVW method indicated a causal relationship between the risk increase of COPD and AAA (OR: 1.47, 95% CI: 1.16 - 1.86, p = 0.001). Among 1400 circulating metabolites, plasma-free proline was identified as mediating the relationship between COPD and AAA, with a mediation effect proportion of −4.6% (95% CI: −9.032%, −0.164%, p = 0.042). Additionally, PPI analysis revealed 20 functionally interrelated genes mediating the linkage between COPD and AAA. KEGG enrichment analysis showed functional enrichment of these genes in the pathway of aldosterone synthesis and secretion. Conclusion: Our study supports a causal relationship between COPD and an increased risk of AAA. Specifically, plasma-free proline and pathways related to aldosterone synthesis and secretion may play key roles in the connection between COPD and AAA.

Kunming mouse strain is less susceptible to elastase-induced abdominal aortic aneurysms

Background:Porcine pancreatic elastase(PPE)is successfully used to induce abdominal aortic aneurysm(AAA)in mice.However,differences between mouse strains in susceptibility to PPE induction have been reported.Kunming mouse is one of the most frequently used strains in China but whether it is suitable for induction of AAA by PPE application remains unclear.Methods:PPE infusion(1.5 units/ml)in temporary controlled aorta was performed to induce AAAs in both C57BL/6J and Kunming mice.Phosphatebuffered saline(PBS)application was used as vehicle control.The aorta diameters of all mice were measured at days 0 and 14 after surgery to evaluate the AAA formation.Results:After 14 days of PPE or PBS infusion,all mice were sacrificed and aorta tissues were collected for histological staining analysis.At the 14th day after infusion,PPE successfully induced aortic dilation in Kunming mice and typical AAA in C57BL/6J mice.The aorta diameter increased by 0.23 mm in Kunming mice after PPE infusion,while it was 0.72 mm in the C57BL/6J strain.PPE induced mild elastin degradation,smooth muscle cell(SMC)depletion and mural leucocyte infiltration in Kunming mice,but in PPE-sensitive C57BL/6J mice,it induced total loss of SMCs,elastin disappearance and diffused infiltrated leucocytes in aortic aneurysmal segments.The effects of PPE in inducing angiogenesis and upregulating matrix metalloproteinase 2 and 9 expression in Kunming mice were also weaker than that in C57BL/6J mice.Conclusion:At the reported dose of PPE,Kunming mouse is not as susceptible to AAA formation as C57BL/6J mice.The failure of PPE to induce AAA formation in Kunming mice may be associated to its inability to boost a strong inflammatory response.

Progression and Regression of Abdominal Aortic Aneurysms in Mice

Objective:Abdominal aortic aneurysm(AAA)is a significant medical problem with a high mortality rate.Nevertheless,the underlying mechanism for the progression and regression of AAA is unknown.Methods:Experimental model of AAA was first created by porcine pancreatic elastase incubation around the infrarenal aorta of C57BL/6 mice.Then,AAA progression and regression were evaluated based on the diameter and volume of AAA.The aortas were harvested for hematoxylin-eosin staining(HE),orcein staining,sirius red staining,immunofluorescence analysis and peris’prussian blue staining at the indicated time point.Finally,P-aminopropionitrile monofumarate(BAPN)was used to explore the underlying mechanism of the regression of AAA.Results:When we extended the observation period to 100 days,we not only observed an increase in the AAA diameter and volume in the early stage,but also a decrease in the late stage.Consistent with AAA diameter and volume,the aortic thickness showed the same tendency based on HE staining.The elastin and collagen content first degraded and then regenerated,which corresponds to the early deterioration and late regression of AAA.Then,endogenous up-regulation of lysyl oxidase(LOX)was detected,accompanying the regression of AAA,as detected by an immunofluorescent assay.BAPN and LOX inhibitor considerably inhibited the regression of AAA,paralleling the degradation of elastin lamella and collagen.Conclusion:Taken together,we tentatively conclude that endogenous re-generation of LOX played an influential role in the regression of AAA.Therefore,regulatory factors on the generation of LOX exhibit promising therapeutic potential against AAA.

Safety and Efficacy of Endovascular Aortic Repair for Abdominal Aortic Aneurysms with a Hostile Neck Anatomy

Objective This study aimed to investigate the safety and efficacy of endovascular aortic repair(EVAR)for the treatment of an abdominal aortic aneurysm(AAA)with a hostile neck anatomy(HNA).Methods From January 1,2015 to December 31,2019,a total of 259 patients diagnosed with an AAA who underwent EVAR were recruited into this study.Based on the morphological characteristics of the proximal neck anatomy,the patients were divided into the HNA group and the friendly neck anatomy(FNA)group.The patients were followed up for up to 4 years.Results The average follow-up time was 1056.1±535.5 days.Type I endoleak occurred in 4 patients in the HNA group,and 2 patients in the FNA group.Neither death nor intraoperative switch to open repair occurred in either group.The time of the operation was significantly longer in the HNA group(FNA vs.HNA,99.2±51.1 min vs.117.5±63.8 min,P=0.011).There were no significant differences in short-term clinical success rate(P=0.228)or midterm clinical success rate(P=0.889)between the two groups.The overall mortality rate was 10.4%,and Kaplan-Meier survival analysis indicated that the two groups had similar cumulative survival rates at the end of the follow-up period(P=0.889).Conclusion EVAR was feasible and safe in patients with an AAA with a proximal HNA.The early and midterm results were promising;however,further studies are needed to verify the long-term effectiveness of EVAR.

Value of digital subtraction angiography in endovascular graft exclusion for abdominal aortic aneurysms

Objective: To evaluate the value of digital subtraction angiography (DSA) in management of endovascular graft exclusion (EVGE) for abdominal aortic aneurysms. Methods: Monitored by DSA and fluoroscopy, stent-graft complex were introduced into the aneurysm sac via femoral arteries and were deployed at the proximal and distal necks to exclude the sac from circulation. Results: The success rate of deployment was 94. 74% (36/38). Endoleaks occurred in 4 cases. One converted to open surgery because of sac rupture 4 days after deployment. Thrombosis and stenosis occurred in 2 cases. Three patients died shortly after the operation (< 3 months). Conclusion: DSA can monitor EVCE on real-time throughout the whole procedure. It can meet the needs of measurement, location, evaluating, detecting, and also can be much helpful in correcting complications. Moreover, it provides large visual field and operating space, and is a very important monitoring method for EVGE.

Standards of endovascular graft exclusion for abdominal aortic aneurysms

Objective: To discuss the standards of endovascular graft exclusion (EVGE) for abdominal aortic aneurysms (AAAs). Methods: The results of our primary experiences for the evidence of standards was summarized. Results: Standards of operating success, cure and procedure failure were put forward. Some relative questions on EVGE were also answered. Conclusion: EVGE is a kind of new conceptive therapy for AAAs in China. More cases should be evaluated in the future to modify it.

Endovascular stent graft repair of abdominal aortic aneurysms:Current status and future directions

Endovascular stent graft repair of abdominal aortic aneurysm(AAA)has undergone rapid developments since it was introduced in the early 1990s.Two main types of aortic stent grafts have been developed and are currently being used in clinical practice to deal with patients with complicated or unsuitable aneurysm necks,namely,suprarenal and fenestrated stent grafts.Helical computed tomography angiography has been widely recognized as the method of choice for both pre-operative planning and post-operative followup of endovascular repair(EVAR).In addition to 2D axial images,a number of 2D and 3D reconstructions are generated to provide additional information about imaging of the stent grafts in relation to the aortic aneurysm diameter and extent,encroachment of stent wires to the renal artery ostium and position of the fenestrated vessel stents.The purpose of this article is to provide an overview of applications of EVAR of AAA and diagnostic applications of 2D and 3D image visualizations in the assessment of treatment outcomes of EVAR.Interference of stent wires with renal blood flow from the hemodynamic point of view will also be discussed,and future directions explored.

Nitric oxide production and inducible nitric oxide synthase protein expression in human abdominal aortic aneurysms and cultured aneurismal smooth muscle cells

Objective：To investigate the production of nitric oxide（NO） and the expression of inducible nitric oxide synthase （iNOS）, and their possible role in abdominal aortic aneurysm （AAA）. Methods： A total of 28 patients with AAA, 10 healthy controls, and 8 patients with arterial occlusive disease were enrolled into this study. Standard colorimetric assay was used to examine NO concentration in plasma from patients with AAA and normal controls, and in cultured smooth muscle cells （SMCs）. Expression of iNOS in aortas and cultured SMCs were detected by immunochemistry. The correlation of iNOS expression with age of the patient, size of aneurysm, and degree of inflammation was also investigated by Cochran-Mantel-Haenszel χ^2 test and Kendall correlation. Results ： Expression of iNOS increased significantly in the wall of aneurism in the patients with AAA compared to the healthy controls （P〈0.05） and the patients with occlusive arteries （P〈0.05）. iNOS protein and media NOx （nitrite＋nitrate） also increased in cultured SMCs from human AAA （n=4, P〈0.05）, while plasma NOx decreased in patients with AAA （n= 25） compared to the healthy controls （n=20）. There was a positive correlation between iNOS protein and the degree of inflammation in aneurismal wall （Kendall coefficient = 0. 5032, P= 0. 0029）. Conclusion： SMCs and inflammatory cells are main cellular sources of increased iNOS in AAA, and NO may play a part in pathogenesis in AAA through inflammation, SMCs and oxidative stress.

Influence of periodontitis on abdominal aortic aneurysms

Periodontitis is known to be a risk factor for abdominal aortic aneurysm(AAA). However, the influence of periodontitis on AAA development is to be elucidated. This article is to review the relationship between periodontitis and AAA. We focused on the roles of specific periodontopathic bacteria in AAA, matrix metalloproteinases and toll-like receptors in the pathophysiology in the section of experimental analysis. Furthermore, we showed clinical data of periodontitis in patients with AAA. We concluded that periodontal pathogens play a critical role in the AAA development.

Elevated plasma level of matrix metalloproteinases-9 and its significance in patients with abdominal aortic aneurysms

Objective: To investigate the changes of the plasma level of MMP-9 (Matrix Metalloproteinase-9, MMP-9) in the patients with abdominal aortic aneurysms (AAAs) before and after the treatment, and evaluate the significance of MMP-9 in the pathogenesis of AAAs. Methods: Blood samples of 35 patients with AAAs and 10 patients with the arterial occlusive diseases (AODs) , which enrolled into the Vascular Surgery Center of Colonge University Hospital from February to August of 2002, were collected before and one month after surgical repair or less-invasive endovascular exclusion. The plasma concentrations of MMP-9 of all the collected samples were measured by means of enzyme-linked immunosorbent assay(ELISA), and compared between the two groups patients at different time point. Results: The mean plasma concentration of MMP-9 of AAAs was significantly higher than that of AODs prior to treatment [(90.3±9.1) ng/ml vs (23.6±7.3) ng/ml, P<0.05], and no apparent difference was showed in the patients with AODs [(23.6±7.3) ng/ml vs (25.3±5.8) ng/ml, P>0.05)] before and after the surgical bypass operation. However, in the patients with AAAs the plasma concentration of MMP-9 was apparently decreased one month after the surgical repair or endovascular exclusion compared with before [(28.6±8.4) ng/ml vs (90.3±9.1) ng/ml, P<0.05)]. No meaningful difference of the mean plasma MMP-9 concentration was seen between two groups after the both being successfully treated [(28.6±8.4) ng/ml vs (25.3±5.8) ng/ml, P>0.05]. Conclusion: Apparent elevation of plasma concentration of MMP-9 in the AAAs and its dramatic decrease after being treated implicated that MMP-9 might play an important role in the formation and development of AAAs. Meanwhile, to investigate the changes of MMP-9 level of AAAs could provide an practical way to facilitate the earlier diagnosis and long term surveillance for AAAs. More importantly, pharmacologic prevention and treatment of AAAs, in which the MMP-9 serves as effective target, might be possible in the future.

Experimental and computational studies on the flow fields in aortic aneurysms associated with deployment of AAA stent-grafts

Pulsatile flow fields in rigid abdominal aortic aneurysm （AAA） models were investigated numerically, and the simulation results are found in good agreement with particle image velocimetry （PIV） measurements. There are one or more vortexes in the AAA bulge, and a fairly high wall shear stress exists at the distal end, and thus the AAA is in danger of rupture. Medical treatment consists of inserting a vascular stent-graft in the AAA, which would decrease the blood impact to the inner walls and reduce wall shear stress so that the rupture could be prevented. A new computational model, based on porous medium model, was developed and results are documented. Therapeutic effect of the stent-graft was verified numerically with the new model.

Abdominal aortic aneurysm： Treatment options, image visualizations and follow-up procedures

Abdominal aortic aneurysm is a common vascular disease that affects elderly population.Open surgical repair is regarded as the gold standard technique for treatment of abdominal aortic aneurysm,however,endovaseular aneurysm repair has rapidly expanded since its first introduction in 1990s.As a less invasive technique,endovascular aneurysm repair has been confirmed to be an effective alternative to open surgical repair,especially in patients with co-morbid conditions.Computed tomography （CT） angiography is currently the preferred imaging modality for both preoperative planning and post-operative follow-up.2D CT images are complemented by a number of 3D reconstructions which enhance the diagnostic applications of CT angiography in both planning and follow-up of endovascular repair.CT has the disadvantage of high cummulative radiation dose,of particular concern in younger patients,since patients require regular imaging follow-ups after endovascular repair,thus,exposing patients to repeated radiation exposure for life.There is a trend to change from CT to ultrasound surveillance of endovascular aneurysm repair.Medical image visualizations demonstrate excellent morphological assessment of aneurysm and stent-grafts,but fail to provide hemodynamic changes caused by the complex stent-graft device that is implanted into the aorta.This article reviews the treatment options of abdominal aortic aneurysm,various image visualization tools,and follow-up procedures with use of different modalities including both imaging and computational fluid dynamics methods.Future directions to improve treatment outcomes in the follow-up of endovascular aneurysm repair are outlined.

High-risk factors related to the occurrence and development of abdominal aortic aneurysm

Abdominal aortic aneurysm(AAA) is a common and potentially dangerous vascular disease with many risk factors related to its occurrence and development. This review collects the results from recent studies of different comorbidities including hypertension, diabetes, and hyperlipidemia and summarizes their connections with AAA development and its underlying mechanisms. We believe that hypertension, diabetes, and hyperlipidemia can affect AAA occurrence and development, but more studies are needed to further explore the mechanisms.

Rapamycin Treatment Attenuates Angiotensin Ⅱ-induced Abdominal Aortic Aneurysm Formation via VSMC Phenotypic Modulation and Down-regulation of ERK1/2 Activity

The aim of the present study is to address the effect of rapamycin on abdominal aortic aneurysm（AAA） and the potential mechanisms. A clinically relevant AAA model was induced in apolipoprotein E-deficient（ApoE-/-） mice, in which miniosmotic pump was implanted subcutaneously to deliver angiotensin Ⅱ（Ang Ⅱ） for 14 days. Male ApoE-/-mice were randomly divided into 3 groups： saline infusion, Ang Ⅱ infusion, and Ang Ⅱ infusion plus intraperitoneal injection of rapamycin. The diameter of the supra-renal abdominal aorta was measured by ultrasonography at the end of the infusion. Then aortic tissue was excised and examined by Western blotting and histoimmunochemistry. Ang Ⅱ with or without rapamycin treatment was applied to the cultured vascular smooth muscle cells（VSMCs） in vitro. The results revealed that rapamycin treatment significantly attenuated the incidence of Ang Ⅱinduced-AAA in ApoE-/-mice. Histologic analysis showed that rapamycin treatment decreased disarray of elastin fibers and VSMCs hyperplasia in the medial layer. Immunochemistry staining and Western blotting documented the increased phospho-ERKl/2 and ERK1/2 expression in aortic walls in Ang Ⅱ induced-AAA,as well as in human lesions. Whereas in the rapamycintreated group, decreased phospho-ERK1/2 expression level was detected. Moreover, rapamycin reversed Ang Ⅱ-induced VSMCs phenotypic change both in vivo and in vitro. Based on those results, we confirmed that rapamycin therapy suppressed Ang Ⅱ-induced AAA formation in mice, partially via VSMCs phenotypic modulation and down-regulation of ERK1/2 activity.

Long Noncoding RNA Expression Signatures of Abdominal Aortic Aneurysm Revealed by Microarray

Objective This study is aimed at observing the role of long noncoding RNAs（lncR NAs） in the pathogenesis of abdominal aortic aneurysm（AAA）.Methods Lnc RNA and m RNA expression signatures of AAA tissues and normal abdominal aortic tissues（NT） were analyzed by microarray and further verified by Real-time quantitative reverse-transcription PCR（q RT-PCR）.The lnc RNAs-m RNAs targeting relationships were identified using computational analysis.The effect of lnc-ARG on 5-lipoxygenase（ALOX5） expression was tested in HeL a cells.Results Differential expressions of 3,688 lncR NAs and 3,007 m RNAs were identified between AAA and NT tissues.Moreover,1,284 differentially expressed long intergenic noncoding RNAs and 206 differentially expressed enhancer-like lnc RNAs adjacent to protein-coding genes were discerned by bioinformatics analysis.Some differentially expressed lncR NAs and m RNAs between AAA and normal tissue samples were further verified using q RT-PCR.A co-expression network of coding and noncoding genes was constructed based on the correlation analysis between the differentially expressed lnc RNAs and mR NAs.In addition,the lnc-ARG located within the upstream of ALOX5 was sorted as a noncoding transcript by analyzing the protein-coding potential using computational analysis.Furthermore,we found that lnc-ARG can decrease the m RNA level of ALOX5 and reactive oxygen species production in He La cells.Conclusion This study revealed new lnc RNA candidates are related to the pathogenesis of AAA.

Identify Can didate Genes in the Interactio n betwee n Abdominal Aortic Aneurysm and Type 2 Diabetes Mellitus by Using Biomedical Discovery Support System

Objective To explore the candidate genes that play significant roles in the interconnection between abdominal aortic aneurysm(AAA)and type 2 diabetes mellitus(DM).Methods We used the Biomedical Discovery Support System(BITOLA)to screen out the candidate intermediate molecular(CIM)"Gene or Gene Product”that are related to AAA and DM.The dataset of GSE13760,GSE7084,GSE57691,GSE47472 were used to analyze the differentially expressed genes(DEGs)of AAA and DM compared to the healthy status.We used the online tool ofVenny 2.1 assisted by manual checking to identify the overlapped DEGs with the CIMs.The Human eFP Browser was applied to examine the tissue specific expression levels of the detected genes in order to recognize strong expressed genes in both human artery and pancreatic tissue.Results There were 86 CIMs suggested by the closed BITOLA system.Among all the DEGs of AAA and DM,8 genes in GSE7084(ISG20,ITGAX,DSTN,CCL5,CCR5,AGTR1,CD19,CD44)and 2 genes in GSE 13760(PSMD12,FAS)were found to be overlapped with the 86 CIMs.By manual checking and comparing with tissuespecific gene data through Human eFP Browser,the gene PSMD12(proteasome 26S subunit,non-ATPase 12)was recognized to be strongly expressed in both the aorta and pancreatic tissue.Conclusion We proposed a hypothesis through text mining that PSMD12 might be involved or potentially involved in the interconnection between AAA and DM,which may provide a new clue for studies on novel therapeutic strategies for the two diseases.

Pheochromocytoma with abdominal aortic aneurysm presenting as recurrent dyspnea,hemoptysis,and hypotension:A case report

BACKGROUND Pheochromocytomas are rare endocrine tumors with various clinical manifestations,and few of them might present with profound,life-threatening conditions.CASE SUMMARY We report the case of a 65-year-old man who complained of sudden dyspnea and hemoptysis for half a day.There was no obvious cause for the patient to have dyspnea,coughing,or coughing up to approximately 100 mL of fresh blood.Finally,he was diagnosed with pheochromocytoma crisis(PCC),coexisting with an abdominal aortic aneurysm(AAA).CONCLUSION We report a case of pheochromocytoma presenting with recurrent hemoptysis,dyspnea and hypotension coexisting with an AAA.It not only proved the uncommon manifestations of pheochromocytoma but also directed clinicians to consider PCC among the possible diagnoses when meeting similar cases.Moreover,surgical excision is the most beneficial method for the treatment of pheochromocytoma coexisting with AAA when the situation is stable.

Innovation in pathogenesis and management of aortic aneurysm

Aortic aneurysm(AA)refers to the persistent dilatation of the aorta,exceeding three centimeters.Investigating the pathophysiology of this condition is important for its prevention and management,given its responsibility for more than 25000 deaths in the United States.AAs are classified based on their location or morphology.various pathophysiologic pathways including inflammation,the immune system and atherosclerosis have been implicated in its development.Inflammatory markers such as transforming growth factorβ,interleukin-1β,tumor necrosis factor-α,matrix metalloproteinase-2 and many more may contribute to this phenomenon.Several genetic disorders such as Marfan syndrome,Ehler-Danlos syndrome and Loeys-Dietz syndrome have also been associated with this disease.Recent years has seen the investigation of novel management of AA,exploring the implication of different immune suppressors,the role of radiation in shrinkage and prevention,as well as minimally invasive and newly hypothesized surgical methods.In this narrative review,we aim to present the new contributing factors involved in pathophysiology of AA.We also highlighted the novel management methods that have demonstrated promising benefits in clinical outcomes of the AA.