Dataset Information

BioSphincters to treat Fecal Incontinence in Nonhuman Primates.

ABSTRACT: Loss of anorectal resting pressure due to internal anal sphincter (IAS) dysfunctionality causes uncontrolled fecal soiling and leads to passive fecal incontinence (FI). The study is focused on immediate and long-term safety and potential efficacy of bioengineered IAS BioSphincters to treat passive FI in a clinically relevant large animal model of passive FI. Passive FI was successfully developed in Non-Human Primates (NHPs) model. The implantation of autologous intrinsically innervated functional constructs resolved the fecal soiling, restored the resting pressure and Recto Anal Inhibitory Reflex (RAIR) within 1-month. These results were sustained with time, and efficacy was preserved up to 12-months. The histological studies validated manometric results with the regeneration of a well-organized neuro-muscular population in IAS. The control groups (non-treated and sham) remained affected by poor anal hygiene, lower resting pressure, and reduced RAIR throughout the study. The pathological assessment of implants, blood, and the vital organs confirmed biocompatibility without any adverse effect after implantation. This regenerative approach of implanting intrinsically innervated IAS BioSphincters has the potential to offer a better quality of life to the patients suffering from FI.

SUBMITTER: Dadhich P

PROVIDER: S-EPMC6888838 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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BioSphincters to treat Fecal Incontinence in Nonhuman Primates.

Dadhich Prabhash P Bohl Jaime L JL Tamburrini Riccardo R Zakhem Elie E Scott Christie C Kock Nancy N Mitchell Erin E Gilliam John J Bitar Khalil N KN

Scientific reports 20191202 1

Loss of anorectal resting pressure due to internal anal sphincter (IAS) dysfunctionality causes uncontrolled fecal soiling and leads to passive fecal incontinence (FI). The study is focused on immediate and long-term safety and potential efficacy of bioengineered IAS BioSphincters to treat passive FI in a clinically relevant large animal model of passive FI. Passive FI was successfully developed in Non-Human Primates (NHPs) model. The implantation of autologous intrinsically innervated functiona ...[more]

PMID: 31792260

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Project description:Introduction and hypothesisTo evaluate change in fecal incontinence symptom severity after 8 weeks of darifenacin therapy in patients with double incontinence-urgency urinary incontinence (UUI) and fecal incontinence. Important secondary outcomes included fecal incontinence symptom distress and impact on quality of life, fecal incontinence episodes, global impression of improvement and overactive bladder symptom distress and impact.MethodsProspective open-label cohort study of women presenting primarily with UUI, diagnosed with double incontinence and electing antimuscarinic therapy for UUI. Women ≥ 18 years with moderate or greater bothersome UUI and fecal incontinence of liquid/solid stool with St. Marks (Vaizey) score ≥ 12 were included. Subjects were treated with darifenacin 15 mg daily for 8 weeks. The primary outcome was change in fecal incontinence symptom severity using the St. Marks (Vaizey) score after 8 weeks. Sample size was based on the minimally important difference of the St. Marks, -5, and standard deviation, ± 8.5; 30 subjects provided 80% power and type I error of 0.05, including a 15% attrition rate.ResultsThirty-two women were consented with mean baseline St. Marks (Vaizey) score of 18.0 ± 3.0. Mean age was 66.5 ± 10.3 years. Twenty-eight subjects (29/32, 87.5%) completed assessments. St. Marks (Vaizey) score significantly improved from 18.0 to 11.0 [mean difference - 7.0, 95% confidence interval (CI): -8.7, -5.3], and 19 subjects (19/32,67.9%) met the minimally important difference. Statistically significant improvements were also noted in fecal incontinence frequency, quality of life, and overactive bladder symptom bother and quality of life (all p < 0.01).ConclusionsDarifenacin can be considered a highly effective early intervention in women suffering from double incontinence.Clinical trial registrationBladder Antimuscarinic Medication and Accidental Bowel Leakage (BAMA), https://clinicaltrials.gov/ct2/show/NCT03543566 , NCT03543566.

Project description:BACKGROUND:In terms of structure and function, the skull is one of the most complicated organs in the body. It is also one of the most important parts in terms of developmental and evolutionary origins. This complexity makes it difficult to obtain evolutionary assessments if, as is usually the case with fossils, only part of the skull is available. For this reason this study involves a set of comparisons whereby the smallest functional units are studied first, and these built up, through a triple-nested hierarchical design, into more complex anatomical regions and eventually into the skull-as-a-whole. This design has been applied to macaques (Macaca) in order to reveal patterns of variation at the different levels. The profiles of such variation have been obtained both within and between species. This has lead to a search for the skull parts that have undergone similar selection pressures during evolution and comparable development patterns in both ontogeny and phylogeny. RESULTS:Morphometric analysis (Principal Components) was used to obtain these profiles of species and sex separations based on 77 cranial variables from 11 species of macaques. The results showed that 7 functional units could be aggregated into three functionally reasonable anatomical regions on the basis of similarities in profiles. These were: the masticatory apparatus containing mandible, lower teeth and upper teeth, the face as a whole combining maxilla (actually lower face) and upper face, and the cranium as a whole involving cranium and calvaria. Twenty-six variables were finally selected for analyzing the morphology of the whole skull. This last showed an overall profile similar to that revealed in the masticatory apparatus but also contained additional information pertaining to individual species and species-groups separations. CONCLUSIONS:The study provides a model for carrying out analysis of species separations and sex variation simultaneously. Through this design it seems possible to see cranio-dental elements that may result from similar developmental processes, have similar functional adaptations, and show an appropriately integrated structure morphologically. This study also implies that the biological information drawn from part of skull alone, e.g. as in studies of incomplete fossils may provide misleading information.

Dataset Information

BioSphincters to treat Fecal Incontinence in Nonhuman Primates.

Publications

BioSphincters to treat Fecal Incontinence in Nonhuman Primates.

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