沙門氏菌感染性動脈瘤：臨床分析及致病機轉研究

Salmonella-associated Infected Aortic Aneurysm: Clinical Analysis and Pathogenesis Research

黃耀廣(Yao-Kuang Huang)

指導教授 ： 吳志雄

共同指導教授 ： 邱政洵

臺北醫學大學/醫學院/臨床醫學研究所/博士(2014年)

摘要

中文摘要
主動脈瘤合併感染，除了手術死亡率及併發症極高外，在尚未手術的感染性主動脈瘤，發生迅速惡化的情況也較一般退化性主動脈瘤高。感染性動脈瘤血管以傳統手術治病的風險非常高。在十二位無法以傳統手術治療的病患身上，我們嘗試用主動脈套膜支架治療，得到了極好的效果，尤其是在沙門氏桿菌感染性主動脈瘤的患者。然而，以主動脈套膜支架來治療感染性主動脈瘤，違反了外科處理感染的原則；我們不但沒有將爛掉的感染組織切掉，更放了一個人工外來物(主動脈套膜支架)在一個嚴重感染的病人身上。本研究第一部分，便是用主動脈套膜支架治療感染性主動脈瘤的經驗整理及啟發。在這十二位病患中，有十位是沙門氏菌引起的主動脈感染(83.3%)。僅有兩位病患死亡(16.7%)，有一位患須要再次手術移除感染的人工血管。
我們同時整理本院感染性動脈瘤，一共有43位病患得到感染性動脈瘤。我們收集病患的資料，分析風險因子、治療選擇及微生物特徵。與國外不同的是，感染性主動脈瘤有相當的比例是由沙門氏菌引起(81.8%)。同時得到以下的結論：術前休克(Hazard ratio=5.50)及豬沙門氏菌血症(Hazard ratio=3.07)是手術死亡的危險因子；沙門氏菌血症(Hazard ratio =4.88) 、自體免疫病(Hazard ratio =4.07)及延遲診斷(Hazard ratio =7.96)是主動脈瘤致死的危險因子；而主動脈支架是除了傳統手術外，感染性主動脈瘤的合理治療選項。
治療沙門氏桿菌感染性主動脈瘤得到的經驗，不禁讓我們聯想到沙門氏桿菌感染可能是藉由異於其他病原的方式，來影響主動脈瘤的病程。我們的團隊接著建立小鼠模式，嘗試用不同的影像學及細菌學追蹤的方式，了解感染性主動脈瘤的致病機轉。其中最重要的技術是發展出穩定發光質體，讓冷光細菌能在活體中即時被監測。我們利用pSE-Lux1(由conjugative plasmid pSE34 及發光基因 luxABCDE operon合成)，得以穩定的追蹤細菌在老鼠活體中的行為。這種發光菌技術不但可以使用在沙門氏菌，還可以應用在其他格蘭氏陰性菌種。
我們期望藉此深入沙門氏菌感染性動脈瘤的致病機轉，能尋出此種致命疾病的新治療方向。

關鍵字

沙門氏菌 ； 感染性 ； 主動脈瘤 ； 血管內治療 ； 泡沫細胞

並列摘要

Abstract:
Infected aortic aneurysms (IAA) are rare, but potentially lethal. This article reviewed our experience in relevant entity and divided into four subtitles.
In the first study:
We review of our initial experience of 12 patients who underwent endovascular repair for infected aortic aneurysm between September 2006 and June 2011. This section focus on appliance of endovascular aortic technique and the therapeutic algorithm developing in this entitle.

In the second study:
To apply backward root analysis to survey independent risk factors associated with bad outcome, microbiologic distribution and impact of different therapeutic options, among all patients with infected aortic aneurysms in our institution. The most frequent causative pathogens were Salmonella (81.8%). The overall mortality in the study was 43.2% (with an aneurysm-related mortality of 18.2%, surgically related mortality of 13.6%, and in-hospital mortality of 22.7%). We conclude that shock is a risk factor for surgical death. Misdiagnosis and treatment of IAA as low back pain, co-existing connective-tissue disease such as systemic lupus erythematosus and rheumatoid arthritis, and Salmonella serogroup C-associated bacteremia are risk factors for aneurysm-related death. Endovascular repair should be considered as an alternative option to the open repair of IAA.

In the third study:
We attempt to survey the behavior of bacteremia in living animal and in aneurysmal mice, to mimic the clinical scenario of infected aortic aneurysm. To achieve this purpose, a stable and conjugative bioluminescence plasmid was developed to facilitate tracing Salmonellae in a living mouse model. This patented plasmid (pSE-Lux1) is also feasible to other Gram-negative microorganisms.

In the further study:
In this section, we disclosed our recent progress of lipid-laden macrophage (foam cells) analysis in vitro.

並列關鍵字

Salmonella ； infected ； aortic aneurysm ； endovascular ； foam cell

參考文獻

References

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