Defining Personalised Management Strategies in Patients with Abdominal Aortic Aneurysms

主动脉是将血液从心脏泵送到身体其他部位的主要血管。腹主动脉位于腹部的部分称为腹主动脉，直径约为20 mm。腹主动脉瘤（AAA）是该部分的异常膨胀至> 30 mm。AAA主要影响退休年龄（>65岁）的男性，但女性也有风险。吸烟和遗传是已知导致AAAs的两个主要因素。如果不及时治疗，AAA会缓慢扩张并最终破裂-这会导致突然发生严重的腹痛和内出血。只有25%的患者能在AAA破裂后存活下来--每年英国约有6,000人，全世界约有20,000人死于AAA破裂。AAA患者在破裂前不会注意到症状。幸运的是，AAA可以很容易地通过超声扫描检测出来。2009年，NHS为65岁以上的男性建立了国家AAA筛查计划（NAAASP）。自该计划开始以来，NAAASP每年诊断出数千名新的AAA患者。此外，类似数量的AAA是偶然从其他医学原因进行的扫描中检测到的。治疗AAA的手术有两种：传统的开放手术是在腹部开一个大口子，直接修复AAA，并用合成织物管代替;一种新的“锁孔”手术是在腹股沟上做微小的切口，将支架从内部覆盖AAA。国际指南建议，（直径在30至54 mm之间）应通过定期超声扫描进行监测，当AAA生长大于55 mm时，应考虑手术。结合起来，这些已被证明可以减少人们死于AAA爆发的机会。为了确保人们在AAA破裂之前接受手术，NHS每年花费数百万美元来监测他们。随着越来越多的病人接受监测，这一费用将继续上升。动脉瘤支架的全球市场也在迅速扩大（到2024年超过30亿英镑），因为越来越多的支架被用于治疗患者。令人担忧的是，在AAA达到55 mm直径之前，在收费医疗保健系统（如德国和美国）中正在进行更多的主动脉支架手术。我最近在牛津大学与数百名AAA患者进行了接触，以了解AAA管理方面对他们最重要的是什么。在AAA监测过程中，“AAA监测频率”成为最重要的问题之一。我还对血管外科医生进行了一项在线国际调查，其中“预测AAA生长的新方法”被选为动脉瘤研究的首要任务。这样的方法并不存在，但对患者和NHS来说将是非常有价值的：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生长的方法，具有良好的准确性。这种方法涉及在常规AAA监测扫描的同时进行额外的血液检查。我还在开发一种通过计算机断层扫描分析来预测AAA生长的方法。这个项目的主要目的是验证我的AAA增长预测方法。我将使用在国际上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扫描进行进一步分析来改进预测方法，以找到其他有用的标记物。最后，我将开发一个即时检测工具包（测量血液）和一个医疗软件（分析CT图像）。这些将使我们的预测方法可用于临床实践。

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.