Pilot Study of Rectal Microbial Biomarkers for Appendicitis Diagnosis

用于诊断阑尾炎的直肠微生物生物标志物的初步研究

基本信息

批准号：
9064769
负责人：
Steven L. Zeichner
金额：
$ 20.71万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-06-01 至 2018-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9064769
关键词：
Abdomen Abdominal Pain Accident and Emergency department Acute Acute Appendicitis Affect Age-Years Appendicitis Biological Markers Blinded Child Childhood Clinical Communities DNA DNA amplification Data Development Diagnosis Diagnostic Diagnostic tests Differential Diagnosis Disease Dose Emergency Department patient Engineering Enrollment Fever Future Genomics Health Health Care Costs Healthcare Systems Image Incidence Investments Laparoscopy Laparotomy Licensing Malignant Neoplasms Medical center Metadata Microbe Minor Multicenter Studies Outcome Patient Care Patients Pelvis Perforated Appendicitis Pilot Projects Population Production Prospective Studies Radiation Rectum Risk Sampling Signs and Symptoms Statistical Models Swab Taxon Technology Testing Time Trauma Ultrasonography X-Ray Computed Tomography abdominal CT base cancer risk cohort cost genomic biomarker girls interest lifetime risk microbial microbiome microbiota novel diagnostics pediatric patients predictive marker predictive modeling prospective rRNA Genes rectal tool

项目摘要

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.

描述（由申请人提供）：阑尾炎是一种常见且昂贵的疾病，在美国每年约有 77,000 名患者被诊断出患有阑尾炎，每年的费用估计为 6.8 亿美元。通常通过超声检查（成本高昂）或腹部 CT（成本高昂，并且使患者受到大量辐射剂量）而日益受到重视，因为最近的估计表明，这会带来重大的长期癌症风险。女孩每次腹部/盆腔儿科 CT 检查导致的终生癌症风险约为 0.3%，我们最近进行的一项研究表明，阑尾的微生物群是不同的。与直肠的微生物群相比，患病阑尾的微生物群与正常阑尾的微生物群不同，最有趣的是，阑尾炎患者的直肠微生物群不同于阑尾炎患者的直肠微生物群。这些研究结果表明，可能存在有用的阑尾炎直肠细菌生物标志物，可以开发成一种快速、更便宜且可能更准确的阑尾炎诊断测试。虽然结果令人兴奋，但还需要更多数据来证实。因此，我们建议对国家儿童医疗中心 (CNMC) 急诊科 (ED) 就诊的患者的直肠微生物群进行前瞻性研究。直肠拭子，分离微生物DNA并获得样本中的16S rRNA基因序列，并收集相关的临床元数据，然后我们将比较评估的CNMC ED患者的直肠微生物群，以排除已确诊阑尾炎的患者与已确诊阑尾炎的患者。根据影像学研究和/或剖腹手术/腹腔镜检查，我们还将可能患有阑尾炎的 ED 患者与正常对照队列（患有急性阑尾炎的患者）的微生物群进行比较。我们将使用直肠微生物群数据创建统计模型，无论是否包含临床元数据，该模型都将根据细菌生物标志物预测阑尾炎的诊断，所提交的研究结论将是证实或反驳我们的假设的数据。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，则基于直肠微生物群生物标志物加上临床元数据的阑尾炎诊断预测模型意义：证实存在直肠细菌生物标志物。阑尾炎微生物生物标志物特征将使阑尾炎微生物诊断测试的未来发展成为可能。阑尾炎直肠细菌生物标志物测试将大大减少不必要的有害辐射暴露，为阑尾炎提供更快速和有效的诊断，并大幅降低医疗保健成本。