Defining Personalised Management Strategies in Patients with Abdominal Aortic Aneurysms

制定腹主动脉瘤患者的个性化治疗策略

• 批准号: MR/V025775/1
• 负责人: Regent Lee
• 金额: $ 194.32万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FV025775%2F1
• 关键词: Defining; Personalised; Management; Strategies; Patients

The aorta is the major blood vessel that pumps blood from the heart to the rest of the body. The part of aorta in the belly is called the abdominal aorta, and should be ~20mm in diameter. An abdominal aortic aneurysm (AAA) is an abnormal ballooning of this section to >30mm. AAA mostly affects men in the retirement age (>65 years old), but women are also at risk. Cigarette smoking and genetics are two of the main factors known to cause AAAs. Left untreated, AAA slowly expands and eventually bursts - this results in sudden onset of severe belly pain and internal bleeding. Only 25% of patients will survive a burst AAA - each year about 6,000 people in the UK and 20,000 people worldwide die from burst AAAs.People with AAAs don't notice symptoms until it bursts. Fortunately, AAAs can be easily detected with an ultrasound scan. In 2009, the NHS established a national AAA screening program (NAAASP) for men over the age of 65. Since the program started, thousands of new AAA patients are diagnosed by the NAAASP each year. In addition, similar numbers of AAAs are detected by chance from scans done for other medical reasons. There are two types of surgery to treat AAAs: traditional open surgery involves a big cut in the belly to directly repair the AAA and replace it with a synthetic fabric tube; newer "keyhole" surgery involves tiny cuts in the groin to put in stents that cover the AAA from inside.International guidelines recommend that patients with small AAAs (between 30 to 54mm in diameter) should be monitored by regular ultrasound scans, and for surgery to be considered when an AAA grows larger than 55mm. In combination, these have been shown to decrease the chance of people dying from burst AAAs. To make sure people undergo surgery before the AAA bursts, the NHS spends millions each year to monitor them. This cost will continue to rise as more patients are being monitored. The global market of aneurysm stents is also expanding rapidly (>£3bn by 2024) as more and more stents are being used to treat patients. Alarmingly, many more aortic stent procedures are being done in fee-for-service health care systems (such as Germany and USA) before the AAA reaches the diameter of 55mm. I recently engaged hundreds of AAA patients at Oxford to see what is most important to them in terms of AAA management. 'Frequency of AAA monitoring' emerged as one of the most important issues during AAA monitoring. I also conducted an online international survey of vascular surgeons, where 'new ways to predict AAA growth' was voted as the top priority for aneurysm research. Such a method did not exist, and would be hugely valuable to the patients and the NHS: It will help clinicians decide how often each patient needs monitoring scans; It will also safeguard patients against unnecessary surgery.I have developed a method for the prediction of AAA growth with good accuracy. This method involves an additional blood test taken at the same time at the routine AAA monitoring scan. I am also developing a method to predict AAA growth by the analysis of computerised tomography scans. This proposed project has the primary aim to validate my method of AAA growth prediction. I will assess the accuracy of my prediction method using patient samples collected at different hospitals, internationally. In addition, I will improve the prediction method by doing further analyses on blood samples and CT scans to find additional markers that can be useful. Lastly, I will develop a point of care testing kit (to measure blood) and a medical software (to analyse CT images). These will make our prediction methods accessible to clinical practice.

主动脉是将血液从心脏输送到身体其他部位的主要血管。腹部主动脉的部分称为腹主动脉，直径应为~20mm。腹主动脉瘤（AAA）是一个异常的膨胀，膨胀到30mm。AAA主要影响退休年龄（65岁左右）的男性，但女性也有风险。吸烟和遗传是已知导致aaa的两个主要因素。如果不及时治疗，AAA会慢慢扩大并最终破裂——这导致突然发作的严重腹痛和内出血。只有25%的患者能在AAA发作后存活——每年英国约有6000人，全世界约有2万人死于AAA发作。患有aaa的人在它爆发之前不会注意到症状。幸运的是，AAAs可以很容易地通过超声扫描检测到。2009年，NHS为65岁以上的男性建立了国家AAA级筛查项目（NAAASP）。自该项目启动以来，每年有数千名新的AAA级患者被NAAASP诊断出来。此外，由于其他医学原因进行的扫描也偶然发现了类似数量的AAAs。治疗AAA的手术有两种：传统的开放式手术是在腹部切开一个大的切口，直接修复AAA，并用合成纤维管代替；较新的“锁眼”手术需要在腹股沟上开个小口子，放入支架，从腹股沟内部覆盖AAA。国际指南建议小AAA（直径在30 - 54mm之间）的患者应通过常规超声扫描监测，当AAA大于55mm时应考虑手术。综合起来，这些已经被证明可以降低人们死于突发aaa的几率。为了确保人们在AAA爆发之前接受手术，NHS每年花费数百万美元来监测他们。随着越来越多的患者接受监测，这一费用将继续上升。随着越来越多的动脉瘤支架被用于治疗患者，动脉瘤支架的全球市场也在迅速扩大（到2024年将达到30亿英镑）。令人担忧的是，在按服务收费的医疗保健系统（如德国和美国），更多的主动脉支架手术是在主动脉瓣直径达到55mm之前完成的。我最近与牛津大学的数百名AAA级患者进行了接触，看看在AAA级管理方面，对他们来说最重要的是什么。“AAA监测频率”成为AAA监测中最重要的问题之一。我还对血管外科医生进行了一项在线国际调查，“预测AAA生长的新方法”被认为是动脉瘤研究的重中之重。这种方法并不存在，而且对患者和NHS都非常有价值：它将帮助临床医生决定每个患者需要监测扫描的频率；它还将保护患者免受不必要的手术。我已经开发了一种预测AAA增长的方法，准确度很高。这种方法包括在常规AAA监测扫描的同时进行额外的血液检查。我还在开发一种方法，通过分析计算机断层扫描来预测AAA的增长。这个项目的主要目的是验证我的AAA增长预测方法。我将使用在国际不同医院收集的患者样本来评估我的预测方法的准确性。此外，我将通过对血液样本和CT扫描的进一步分析来改进预测方法，以找到其他有用的标记。最后，我将开发一个护理点测试套件（用于测量血液）和一个医疗软件（用于分析CT图像）。这将使我们的预测方法可用于临床实践。

项目成果

Interferon regulatory factor-5-dependent CD11c+ macrophages contribute to the formation of rupture-prone atherosclerotic plaques.

• DOI: 10.1093/eurheartj/ehab920
• 发表时间: 2022-05-14
• 期刊: EUROPEAN HEART JOURNAL
• 影响因子: 39.3
• 作者: Edsfeldt, Andreas;Swart, Maarten;Singh, Pratibha;Dib, Lea;Sun, Jiangming;Cole, Jennifer E;Park, Inhye;Al-Sharify, Dania;Persson, Ana;Nitulescu, Mihaela;Das Neves Borges, Patricia;Kassiteridi, Christina;Goddard, Michael E;Lee, Regent;Volkov, Petr;Orho-Melander, Marju;Maegdefessel, Lars;Nilsson, Jan;Udalova, Irina;Goncalves, Isabel;Monaco, Claudia
• 通讯作者: Monaco, Claudia

Prediction of Abdominal Aortic Aneurysm Growth Using Geometric Assessment of Computerized Tomography Images Acquired During the Aneurysm Surveillance Period.

• DOI: 10.1097/sla.0000000000004711
• 发表时间: 2023-01-01
• 期刊: Annals of surgery
• 影响因子: 9
• 作者: Chandrashekar A;Handa A;Lapolla P;Shivakumar N;Ngetich E;Grau V;Lee R
• 通讯作者: Lee R

A histopathological classification scheme for abdominal aortic aneurysm disease.

• DOI: 10.1016/j.jvssci.2021.09.001
• 发表时间: 2021
• 期刊: JVS-vascular science
• 作者: Bruijn LE;van Stroe Gómez CG;Curci JA;Golledge J;Hamming JF;Jones GT;Lee R;Matic L;van Rhijn C;Vriens PW;Wågsäter D;Xu B;Yamanouchi D;Lindeman JH
• 通讯作者: Lindeman JH

A Deep Learning Approach to Visualize Aortic Aneurysm Morphology Without the Use of Intravenous Contrast Agents.

• DOI: 10.1097/sla.0000000000004835
• 发表时间: 2023-02-01
• 期刊: Annals of surgery
• 影响因子: 9
• 作者: Chandrashekar A;Handa A;Lapolla P;Shivakumar N;Uberoi R;Grau V;Lee R
• 通讯作者: Lee R

Protective Role for Smooth Muscle Cell Hepcidin in Abdominal Aortic Aneurysm.

• DOI: 10.1161/atvbaha.123.319224
• 发表时间: 2023-05
• 期刊: ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
• 影响因子: 8.7
• 作者: Loick, Paul;Mohammad, Goran Hamid;Cassimjee, Ismail;Chandrashekar, Anirudh;Lapolla, Pierfrancesco;Carrington, Alison;Vera-Aviles, Mayra;Handa, Ashok;Lee, Regent;Lakhal-Littleton, Samira
• 通讯作者: Lakhal-Littleton, Samira