Defecation mechanisms and subtyping of constipation patients with Fecobionics

Fecobionics对便秘患者的排便机制和分型

• 批准号: 10211784
• 负责人: Hans Gregersen
• 金额: $ 64.56万
• 依托单位: CALIFORNIA MEDICAL INNOVATIONS INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-15 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10211784
• 关键词: Affect; Anal canal; Anus; Area; Barium; Biomechanics; Chronic; Circular layer of muscularis propria of anal canal; Colorectal; Conflict (Psychology); Constipation; Data; Defecation; Defecography; Defect; Development; Devices; Diagnosis; Diagnostic; Diagnostic tests; Disease; Etiology; Event; Expenditure; External anal sphincter structure; Feces; Friction; Functional disorder; Future; Geometry; Goals; Health; Health Care Costs; Human; Incidence; Innovative Therapy; Intra-abdominal; Knowledge; Laboratories; Lead; Length; Location; Manometry; Maps; Medicine; Methods; Modality; Motor; Muscle; North America; Patients; Pattern; Pelvic Floor Muscle; Peristalsis; Persons; Physiological; Physiology; Play; Population; Privatization; Process; Property; Radiation; Records; Rectum; Reflex action; Relaxation; Research; Resolution; Risk; Role; Sensory; Shapes; Skeletal Muscle; Smooth Muscle; Sphincter; Stress; Symptoms; System; Test Result; Testing; Therapeutic; Thinking; Time; Treatment outcome; Valsalva Maneuver; Wireless Technology; abdominal pressure; abdominal wall; anorectal disorder; biomechanical model; cell motility; clinical decision-making; cost; driving force; improved; insight; laxative; mathematical model; motility disorder; novel; outcome prediction; pressure; rectal; sphincter ani muscle structure; symptom treatment; tool; treatment strategy; vector; viscoelasticity

ABSTRACT Chronic constipation (CC) is a common condition that affects up to 25% of the population in North America with rising incidence that poses a major burden on the healthcare cost. The pathophysiology of this condition is poorly understood and consequently there are inadequate treatments. The significant problems are, 1) incomplete understanding of the defecation reflex and 2) lack of physiologically relevant and practical diagnostic test for identifying the underlying mechanism(s). Current diagnostic tests provide incomplete and often conflicting information. Not surprisingly, results of these tests correlate poorly with symptoms and treatment outcomes. Our objective is to provide an improved understanding of the continence mechanisms and defecation patterns in healthy subjects and patients with CC using a novel Fecobionics device for mapping the geometric and manometric profiles during evacuation. Fecobionics is an electronic simulated stool that has the consistency and shape of normal stool. The device records pressures, cross-sectional area, orientation, bending, shape, and viscoelastic properties of the rectum and anal canal simultaneously. Our central hypothesis is that rectal peristalsis is a key component of the defecatory reflex which is not assessed in the current paradigm of diagnostic testing. The novel Fecobionics device will mimic the natural defecation and provide new mechanistic insights into the anorectal physiology and pathophysiology to facilitate the development of new treatments for CC. Fecobionics can provide complete picture of the normal defecation pattern (“signatures”) that includes rectal peristaltic reflex, deformability of the device and distensibility of the anal sphincters in healthy subjects and patients with various subtypes of CC. The Specific Aims are as follows: 1) Study the defecation dynamics in normal control subjects using Fecobionics. We will establish the role of rectal contraction/peristalsis in the normal evacuation process. 2) Define the defecatory patterns in patients with CC associated with defecatory disorders. We will determine if abnormalities of rectal contraction contribute to the CC. 3) Use a mathematical model of anorectal passage of Fecobionics for enhanced understanding of the normal and abnormal defecatory patterns, including the length-tension properties of the rectum and anal sphincter muscles. Our proposal seeks to shift current CC research by providing a stool surrogate for examining the physiologic parameters of defecation reflex using a novel device that will record, pressure, deformability, biomechanics, vectoral and topographic changes in the rectum and anal canal. The noted parameters will be recorded using a wireless Fecobionics device that can examine in detail the mechanistic underpinnings (stress and deformation) of defecation reflex/process in health and disease. The impact of this project is that it assesses a novel, safe, low cost, less invasive, low-risk, radiation-free device in its ability to provide better understanding of evacuation and continence mechanisms and thereby facilitate future development of innovative therapies. The improvement can lead to improvement in diagnostic and therapeutic modalities and reduce healthcare costs associated with anorectal disorders.

摘要 慢性便秘(CC)是一种常见的疾病，在北美有高达25%的人口患有 发病率上升，这对医疗成本构成了重大负担。这种情况的病理生理学是 缺乏了解，因此没有适当的治疗方法。主要问题有：1) 对排便反射的认识不全面；2)缺乏生理学相关性和实用性 用于确定潜在机制的诊断试验(S)。目前的诊断测试提供不完整的和 经常是相互冲突的信息。不足为奇的是，这些测试的结果与症状和 治疗结果。我们的目标是提供对控制机制的更好的理解 使用一种新型的生物标测设备研究健康受试者和CC患者的排便模式 疏散过程中的几何和测压剖面。生物仿生学是一种电子模拟凳子，它有 正常大便的稠度和形状。该装置记录压力、横截面积、方位、 直肠和肛管同时的弯曲、形状和粘弹性特性。我们的中央 假说是直肠蠕动是排便反射的一个关键组成部分，这一点在 当前诊断测试的范例。这种新型的生物仿生装置将模拟自然排便和 为肛门直肠生理学和病理生理学提供新的机械学见解，以促进 发展CC的新治疗方法。排便仿生学可以提供正常排便的完整图像 包括直肠蠕动反射、装置的变形性和装置的扩张性 正常人和CC各亚型患者的肛门括约肌。具体目标如下 1)用生物仿生学方法研究正常对照组的排便动力学。我们将建立 直肠收缩/蠕动在正常排空过程中的作用。2)在中定义排便模式 合并排便障碍的CC患者。我们将确定直肠收缩是否异常 对CC作出贡献。3)利用生物仿生学的肛门直肠通道数学模型进行增强 了解正常和异常的排便模式，包括大便的长度-张力特性 直肠和肛门括约肌。我们的建议旨在通过提供凳子来改变当前的CC研究 使用一种新型的记录装置检测排便反射的生理参数的替代物， 直肠和肛管的压力、变形性、生物力学、矢状和地形性变化。这个 记录的参数将使用无线仿生设备进行记录，该设备可以详细检查 健康和疾病中排便反射/过程的机械基础(应力和变形)。这个 该项目的影响在于，它评估了一种新颖、安全、低成本、侵入性较小、低风险、无辐射的设备 它能够更好地了解疏散和控制机制，从而促进 创新疗法的未来发展。该改进可导致诊断和 治疗方式和降低与肛门直肠疾病相关的医疗成本。