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名患者每年被诊断出患有阑尾炎，估计每年6.8亿美元。评估了更多的患者，以排除阑尾炎，通常是通过超声检查，这是昂贵的，或者是腹部CT，这既是昂贵又是受试者患有大放射剂剂量的患者，这越来越多地被视为具有重大长期癌症风险的优势。最近的估计表明，女孩在每个腹部/骨盆小儿CT检查中，终生癌症风险约为0.3％。显然需要一种更好，更准确的方法来诊断阑尾炎。我们最近进行了一项研究，该研究表明，附录的菌群与直肠的菌群不同，disseped乱的附录的菌群与正常阑尾的菌群不同，最有趣的是，最有趣的是，阑尾病的直肠菌群不同。这些发现表明，对照患者可能会有有用的直肠菌群。这些发现表明，结果中看到的患者可能有有用的直肠菌群令人兴奋，需要更多数据来确认可以在直肠细菌群落中鉴定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，研究儿童国家医疗中心（CNMC）急诊科（ED）中的患者的直肠菌群。我们将通过直肠拭子，分离微生物DNA并获得样品中的16S rRNA基因序列，并收集相关的临床元数据。然后，我们将根据成像研究和/或腹腔切开术/或腹腔镜检查，比较评估的CNMC ED患者的直肠菌群与排除阑尾炎排除的阑尾炎的阑尾炎。我们还将比较ED患者的阑尾炎的微生物群和正常对照组，患有急性小型创伤的患者。我们将使用直肠微生物群数据创建统计模型，其中有或不包含临床元数据，该模型将预测基于细菌生物标志物的阑尾炎诊断。拟议研究结论的可交付的数据将是确认或驳斥我们的假设意义的数据：确认存在于阑尾炎的直肠微生物生物标记物，如果我们确认我们的假设I确认，则是基于直肠微生物群生物标志物以及临床临床末端的阑尾炎诊断的预测模型。意义：确认阑尾炎有直肠微生物生物标志物特征将使未来开发阑尾炎的微生物诊断测试。直肠细菌的阑尾炎生物标志物测试将大大减少不必要的有害辐射暴露，为阑尾炎提供更快有效的诊断，并大大降低医疗保健成本。