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

• 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
• 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

 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名患者被诊断患有阑尾炎，每年的费用估计为6.8亿美元。通常通过昂贵的超声波检查或腹部CT对多倍的患者进行评估以排除阑尾炎，腹部CT既昂贵又使患者受到大的辐射剂量，这越来越被认为是造成显著的长期癌症风险。最近的估计表明，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%。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，阑尾的微生物群与直肠的微生物群不同，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与正常阑尾的微生物群不同。 对照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，可以开发成快速，更便宜，可能更准确的阑尾炎诊断测试。虽然结果令人兴奋，但需要更多的数据来证实阑尾炎的生物标志物可以在直肠细菌群落中识别。因此，我们建议进行一项前瞻性研究，检查在儿童国家医学中心（CNMC）急诊科（艾德）就诊的患者的直肠微生物群。我们将通过直肠拭子获取样本，分离微生物DNA并获得样本中的16 S rRNA基因序列，并收集相关临床元数据。然后，我们将比较CNMC艾德患者的直肠微生物群，根据影像学研究和/或剖腹术/腹腔镜检查，排除阑尾炎的患者与排除阑尾炎的患者。我们还将比较可能患有阑尾炎的艾德患者与正常对照组的微生物群，患者表现为急性轻微创伤。我们将使用直肠微生物群数据创建统计模型，包括或不包括基于细菌生物标志物预测阑尾炎诊断的临床元数据。在拟议研究结束时的可交付成果将是证实或反驳我们关于阑尾炎存在直肠细菌生物标志物的假设的数据，并且如果我们的假设得到证实，则是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的预测模型。 重要性：确认存在阑尾炎的直肠微生物生物标志物特征将使未来能够开发阑尾炎的微生物诊断测试。阑尾炎的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有效的诊断，并大大降低医疗保健成本。