Pilot Study of Rectal Microbial Biomarkers for Appendicitis Diagnosis

 描述(申请人提供)：阑尾炎是一种常见且代价高昂的疾病。在美国，每年约有7.7万名患者被诊断为阑尾炎，每年的成本估计为6.8亿美元。更多的患者接受评估以排除阑尾炎，通常是通过昂贵的超声波检查，或者通过腹部CT检查，后者既昂贵，又使患者受到大剂量的辐射，越来越多的人认为这会带来重大的长期癌症风险。最近的估计表明，女孩的每一次腹部/盆腔CT检查都会导致约0.3%的终身癌症风险。显然需要一种更好、更准确的方法来诊断阑尾炎。我们最近进行的一项研究表明，阑尾的微生物区系与直肠的微生物区系不同，病变阑尾的微生物区系与正常阑尾的微生物区系不同，最有趣的是，阑尾炎患者的直肠微生物区系与直肠的微生物区系不同。 对照组患者的直肠微生物区系。这些发现表明，阑尾炎的直肠细菌生物标志物可能是有用的，可以开发成一种快速、廉价和潜在更准确的阑尾炎诊断试验。虽然结果是令人兴奋的，但还需要更多的数据来证实在直肠细菌群落中可以识别出阑尾炎的生物标志物。因此，我们建议进行一项前瞻性研究，检查在国家儿童医学中心(CNMC)急诊科(ED)就诊的患者的直肠微生物区系。我们将通过直肠拭子采集样本，分离微生物DNA，获得样本中的16S rRNA基因序列，并收集相关的临床元数据。然后，我们将根据影像研究和/或开腹/腹腔镜检查，比较CNMC ED患者的直肠微生物区系，以排除阑尾炎和排除阑尾炎的患者。我们还将比较可能患有阑尾炎的ED患者和表现为急性轻微创伤的正常对照组患者的微生物区系。我们将使用直肠微生物区系数据创建统计模型，包括和不包括临床元数据，这些元数据将基于细菌生物标记物预测阑尾炎诊断。在拟议的研究结束时，可交付的数据将证实或驳斥我们的假设，即存在阑尾炎的直肠细菌生物标志物，如果我们的假设得到证实，则将基于直肠微生物区系生物标志物加上临床元数据建立阑尾炎诊断的预测模型。意义：确认有阑尾炎的直肠微生物生物标志物特征将有助于未来阑尾炎微生物诊断试验的发展。阑尾炎的直肠细菌生物标志物检测将大大减少不必要的有害辐射暴露，为阑尾炎提供更快速有效的诊断，并显著降低医疗费用。

 DESCRIPTION (provided by applicant): Appendicitis is a common and costly disease. About 77,000 patients are diagnosed with appendicitis each year in the US, with annual costs estimated at $680 million/year. Many-fold more patients are evaluated to rule out appendicitis, typically by ultrasonography, which is costly, or by abdominal CT, which is both costly and subjects patients to large radiation doses, which are increasingly appreciated as posing significant long term cancer risks. Recent estimates suggest a ~0.3% lifetime cancer risk resulting from each abdominal/pelvic pediatric CT exam in girls. A better and more accurate approach to the diagnosis of appendicitis is clearly needed. We recently conducted a study that showed that the microbiota of the appendix is different than the microbiota of the rectum, that the microbiota of the diseased appendix is different than the microbiota of the normal appendix and, most interestingly, that the rectal microbiota of patients with appendicitis differed from the rectal microbiota of control patients. These findings suggest that there might be useful rectal bacterial biomarkers for appendicitis that could be developed into a rapid, cheaper and potentially more accurate diagnostic test for appendicitis. While the results are exciting, more data are needed to confirm that biomarkers for appendicitis can be identified in the rectal bacterial communities. We therefore propose to conduct a prospective study examining the rectal microbiota of patients seen in the Children's National Medical Center (CNMC) Emergency Department (ED). We will obtain samples by rectal swab, isolate microbial DNA and obtain the 16S rRNA gene sequences in the sample, and collect associated clinical metadata. We will then compare the rectal microbiota of CNMC ED patients evaluated to rule out appendicitis who have appendicitis ruled in with those who have appendicitis ruled out, based on imaging studies and/or laparotomy/laparoscopy. We will also compare the microbiota of the ED patients with possible appendicitis with a normal control cohort, patients presenting with acute minor trauma. We will create statistical models using the rectal microbiota data, with and without inclusion of clinical metadata that will predict appendicitis diagnosis based on bacterial biomarkers. The deliverable at the conclusion of the proposed study will be data that either confirms or refutes our hypothesis that there are rectal bacterial biomarkers for appendicitis and, if our hypothesis i confirmed, a predictive model for appendicitis diagnosis based on the rectal microbiota biomarkers plus clinical metadata. Significance: Confirmation that there are rectal microbial biomarker signatures for appendicitis will enable future development of a microbial diagnostic test for appendicitis. A rectal bacterial biomarker test for appendicitis would substantially reduc unnecessary harmful radiation exposure, provide more rapid and effective diagnosis for appendicitis, and substantially reduce health care costs.