5 CREATION OF A CHRONIC PERIANAL CROHN’S FISTULA IN SWINE

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S5-S5
Author(s):  
Ling Li ◽  
Leonardo Duraes ◽  
Susan Gearhart ◽  
Atif Zaheer ◽  
Haijie Hu ◽  
...  

Abstract Introduction Perianal Crohn’s disease (PCD) is associated with worse outcomes including poor quality of life and higher medical costs. PCD is notoriously difficult to treat despite advancements in biologic therapies for luminal disease. In order to test innovative therapies for PCD, an animal model that closely mimics human perianal disease is warranted. Previous efforts were successful in creating perianal fistulas in swine, however, these closed after removal of the seton. A chronic model that maintains the fistula open and replicates the inflammatory component found in clinic is necessary. Methods Under general anesthesia, 4 female pigs underwent creation of surgical perianal fistulas using basic surgical technique with scalpel and hemostat. Size 24 French silicone foley catheter setons were placed to maintain patency of the fistula tract. Each pig had 3 fistulas created – 1 rectovaginal and 2 perianal. The setons were left in place for 4 weeks. After removal of the setons, Trinitrobenzenesulfonic acid (TNBS) was administered into the fistula tract twice a week to create local inflammation. After 2 weeks of TNBS, an MRI was obtained to assess the fistula tracts and the pigs were sacrificed to review histopathology. Results MRI showed successful creation of chronic fistula tracts, and maintenance of these tracts 2 weeks after removal of setons. We noted a transsphincteric fistula with supralevator component as well as an associated abscess 3.3 x 1.0 cm containing fluid and gas (Fig 1). Gross specimen revealed patent fistula tracts. Histopathology found significant chronic active inflammation on standard H&E staining (Fig 2). Conclusions A chronic perianal fistula model in pigs was successfully created using large bore rubber setons and TNBS stimulation that strongly resembles that seen in humans. Further studies are needed to standardize the conditions required to have a reproducible model with well-defined levels of inflammation, fistula patency, and other parameters.

Author(s):  
Samuel O. Adegbola ◽  
Lesley Dibley ◽  
Kapil Sahnan ◽  
Tiffany Wade ◽  
Azmina Verjee ◽  
...  

Abstract Background Perianal fistulas are a challenging manifestation of Crohn’s disease. Best medical and surgical therapy results in only about a third of patients remaining in remission at one year on maintenance treatment and sustained healing is often elusive. There is little published data on patient perspective of living with the condition or coping strategies in the face of non-curative/non-definitive treatment. We aimed to understand the experience of living with perianal fistula(s) and their impact on quality of life and routine functioning. Methods This exploratory qualitative study used purposive sampling to recruit participants with current / previous diagnosis of Crohn’s anal fistulas, from national IBD / bowel disease charities. The “standards for reporting qualitative research” (SRQR) recommendations were followed. Unstructured individual face-to-face interviews were audio recorded, transcribed and analysed thematically. Early themes were reviewed by the study team including patient advocates, clinicians and qualitative researchers. Results Twelve interviews were conducted, achieving apparent data saturation. Three broad themes were uncovered: Burden of symptoms; Burden of treatment; and Impact on emotional, physical and social well-being. Each included several sub-themes, with considerable interplay between these. The impact of perianal fistula(s) on patients with CD is intense and wide reaching, negatively affecting intimate, close and social relationships. Fistulas cause losses in life and work-related opportunities, and treatments can be difficult to tolerate. Conclusion Crohn’s perianal fistulas exert a heavy negative physical and emotional impact on patients. These findings will inform development of a patient reported outcome measure to assess treatment effectiveness and quality of life for patients living with this challenging condition.


2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S174-S174 ◽  
Author(s):  
S Adegbola ◽  
M Sarafian ◽  
K Sahnan ◽  
P Tozer ◽  
N Ding ◽  
...  

Abstract Background The reasons why fistulas originate have been explained in idiopathic cases, with the cryptoglandular theory being widely accepted; however, in Crohn ́s disease, it is thought to involve interplay between microbiological, immunological and genetic factors. It remains unclear why fistulas persist. Novel investigative tools in systems biology are improving our understanding of pathogenesis, and one such tool is metabonomic profiling, whereby spectrometry is used to assess metabolic responses of complex systems in health and disease. These changes are mapped using analytical and statistical techniques. To the best our knowledge, these methodologies have not been applied to aid understanding of the pathogenesis of Crohn’s perianal fistula persistence. Methods Fistula tissue biopsy was obtained from the fistula tract of 30 patients with idiopathic perianal fistula and 20 patients with Crohn ́s anal fistula. Two analytical platforms were attempted to achieve broad metabolome coverage. Univariate (student t-test) and multivariate statistical data analyses were performed. From the latter principle component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA), models were built to find metabolites that could predict tissue samples from patients with either Crohn’s or idiopathic anal fistula. Metabolite putative identification was conducted by matching accurate mass:charge ratio (m/z) measurements of detected chromatographic features to theoretical value from in-house databases and on-line databases and previous publications. Results Significant OPLS-DA predictive models (validated with CV-ANOVA p-value <0.05) differentiated metabolites from tissue samples from Crohn’s vs. idiopathic anal fistula patients using both metabonomic profiling platforms (HILIC/lipid profiling). A total of 22 differentiating metabolites were identified from the HILIC profiling and 19 from the lipid profiling analysis. Mapped pathway analysis was performed for metabolites identified using online database searches. Conclusion Forty-one differentiating metabolites were discovered belonging to various classes of lipids, amino acids and nucleotides. Pathways involved included amino acid metabolism, phospholipid metabolism and glycerolipid metabolism amongst others. Further work in larger numbers is required to validate these findings as well as cross correlation with microbiome work to understand the impact of host gut interactions in the pathophysiology of Crohn’s and idiopathic perianal fistulas.


2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S428-S428
Author(s):  
S Adegbola ◽  
L Dibley ◽  
K Sahnan ◽  
P Tozer ◽  
T Wade ◽  
...  

Abstract Background Crohn’s perianal fistulas are challenging for patients and clinicians. Many do not respond to available treatments, and despite recommendations by a recent global consensus, there are currently no specific patient-derived quality of life (QoL) tools to measure outcomes including response to treatment, in patients with Crohn’s perianal fistulas. Exploratory qualitative work has demonstrated that Crohn’s perianal fistulas reduce QoL far beyond restricting daily and sexual activities, and a patient-centred, patient-derived tool is needed. We present a patient-reported outcomes measure (PROM) for this complicated disease phenotype. Methods A 35 item draft questionnaire was generated using information from: (a) unstructured qualitative patient interviews, exploring the experience of living with Crohn’s perianal fistulas; (b) a consensus exercise analysing outcomes from a systematic review of studies assessing medical, surgical and combined (medical/surgical) treatment of Crohn’s perianal fistula; and (c) a patient and public involvement meeting. Psychometric properties were assessed including construct validity (by comparison with the Hospital Anxiety and Depression Scale, HADS and the United Kingdom version of the Inflammatory Bowel Disease Questionnaire, UK-IBDQ), and reliability and responsiveness assessed by test-retest analysis. Results Data from 211 patients contributed to the development of the CAF-QoL scale, following the collation of items including patient experience interviews, a systematic review and a consensus exercise involving 187 stakeholders (patients, gastroenterologists, surgeons, IBD specialist nurses, radiologists). Internal consistency was good with Cronbach’s α of 0.88. Analysis aided reduction of the questionnaire to 26 items that demonstrated good internal consistency, good stability (intra-class correlation 0.98) and good construct validity and responsiveness with positive correlation with the UK IBDQ and HADS. Conclusion A disease-specific PROM to assess clinical outcome (i.e. QoL) as baseline and following interventions in patients with Crohn’s anal fistula—the CAF-QoL—is ready for use. Translation and cross-cultural validation will aid wider international dissemination.


2021 ◽  
Vol 49 (2) ◽  
pp. 030006052098666
Author(s):  
Marcin Włodarczyk ◽  
Jakub Włodarczyk ◽  
Aleksandra Sobolewska-Włodarczyk ◽  
Radzisław Trzciński ◽  
Łukasz Dziki ◽  
...  

Cryptoglandular perianal fistula is a common benign anorectal disorder that is managed mainly with surgery. A fistula is typically defined as a pathological communication between two epithelialized surfaces. More specifically, perianal fistula manifests as an abnormal tract between the anorectal canal and the perianal skin. Perianal fistulas are often characterized by significantly decreased patient quality of life. The cryptoglandular theory of perianal fistulas suggests their development from the proctodeal glands, which originate from the intersphincteric plane and perforate the internal sphincter with their ducts. Involvement of proctodeal glands in the inflammatory process could play a primary role in the formation of cryptoglandular perianal fistula. The objective of this narrative review was to investigate the current knowledge of the pathogenesis of cryptoglandular perianal fistula with the specific aims of characterizing the potential role of proinflammatory factors responsible for the development of chronic inflammation. Further studies are crucial to improve the therapeutic management of cryptoglandular perianal fistulas.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Michaela Tencerova ◽  
Lilli Lundby ◽  
Steen Buntzen ◽  
Stig Norderval ◽  
Helene Tarri Hougaard ◽  
...  

Abstract Background Injection of autologous adipose tissue (AT) has recently been demonstrated to be an effective and safe treatment for anal fistulas. AT mesenchymal stem cells (AT-MSCs) mediate the healing process, but the relationship between molecular characteristics of AT-MSCs of the injected AT and fistula healing has not been adequately studied. Thus we aimed to characterize the molecular and functional properties of AT-MSCs isolated from autologous AT injected as a treatment of cryptogenic high transsphincteric perianal fistulas and correlate these findings to the healing process. Methods 27 patients (age 45 ± 2 years) diagnosed with perianal fistula were enrolled in the study and treated with autologous AT injected around the anal fistula tract. AT-MSCs were isolated for cellular and molecular analyses. The fistula healing was evaluated by MRI scanning after 6 months of treatment. AT-MSC phenotype was compared between responders and non-responders with respect to fistula healing. Results 52% of all patients exhibited clinical healing of the fistulas as evaluated 6 months after last injection. Cultured AT-MSCs in the responder group had a lower short-term proliferation rate and higher osteoblast differentiation potential compared to non-responder AT-MSCs. On the other hand, adipocyte differentiation potential of AT-MSCs was higher in non-responder group. Interestingly, AT-MSCs of responders exhibited lower expression of inflammatory and senescence associated genes such as IL1B, NFKB, CDKN2A, TPB3,TGFB1. Conclusion Our data suggest that cellular quality of the injected AT-MSCs including cell proliferation, differentiation capacity and secretion of proinflammatory molecules may provide a possible mechanism underlying fistula healing. Furthermore, these biomarkers may be useful to predict a positive fistula healing outcome. Trial registration: NTC04834609, Registered 6 April 2021. https://clinicaltrials.gov/ct2/show/NCT04834609


2020 ◽  
pp. 34-36
Author(s):  
M. A. Pokhaznikova ◽  
E. A. Andreeva ◽  
O. Yu. Kuznetsova

The article discusses the experience of teaching and conducting spirometry of general practitioners as part of the RESPECT study (RESearch on the PrEvalence and the diagnosis of COPD and its Tobacco-related aetiology). A total of 33 trained in spirometry general practitioners performed a study of 3119 patients. Quality criteria met 84.1% of spirometric studies. The analysis of the most common mistakes made by doctors during the forced expiratory maneuver is included. The most frequent errors were expiration exhalation of less than 6s (54%), non-maximal effort throughout the test and lack of reproducibility (11.3%). Independent predictors of poor spirogram quality were male gender, obstruction (FEV1 /FVC<0.7), and the center where the study was performed. The number of good-quality spirograms ranged from 96.1% (95% CI 83.2–110.4) to 59.8% (95% CI 49.6–71.4) depending on the center. Subsequently, an analysis of the reasons behind the poor quality of research in individual centers was conducted and the identified shortcomings were eliminated. The poor quality of the spirograms was associated either with the errors of the doctors who undertook the study or with the technical malfunctions of the spirometer.


2019 ◽  
Vol 7 (3) ◽  
pp. 232-237
Author(s):  
Hana Larasati ◽  
Theresia Titin Marlina

Background: stroke is a disorder of nervous system function that occurs suddenly and is caused by brain bleeding disorders that can affect the quality of life physical dimensions, social dimensions, psychological dimensions, environmental dimensions. Based on the result of Lumbu study (2015) the number of samples were 71 people collected data using the (WHOQOL-BREF). There were 56 people (78,9%) had the poor quality of life of post stroke. The mean of post-stroke quality of life domain was physical domain (45,27%), psychological domain (49,87%), social relations domain (48,15%) and environmental domain (50.01%). Objective: the purpose of the study was know the quality of life of the stroke patients in Outpatient Polyclinic of Private Hospital in Yogyakarta. Methods: used descriptive quantitative by using questionnaire test of purposive sampling system based on patients who have been affected of ischemic or hemorrhagic stroke before, number 30 respondents. Result: quality of life of stroke patient of medium physical dimension (67%), psychological dimension (71%), social dimension (67%), dimension good environment (63%). Conclusion: the quality of life of stroke patients of physical dimension, psychological dimension, and moderate social dimension, while the quality of life of stroke patients were good environmental dimension.   Keywords: Hemorrhagic stroke, ischemic stroke, quality of life


2020 ◽  
pp. 3-53
Author(s):  
Yu.B. Vinslav

The article analyzes the main indicators of the evolution of the domestic economy and its industrial complex in the past year (in January — November 2019). It Identifies trends in this evolution, including negative trends that determine the preservation of reproductive threats in 2020: sluggishness, instability and low quality of economic growth. The main reasons for the fact that the objective resource capabilities of the macro level were clearly not used enough to effectively solve the urgent problems of technological modernization of the economy and increase people’s welfare are established. The main reason is the poor quality of public administration, including imperfect strategic planning and industrial policy; there is still no modern national innovation system in the country. Accordingly, recommendations for improving the quality of state regulation in its specified components are justified. The recommended measures, according to the author, will help the economy to move to a trajectory of rapid, sustainable and high-quality growth.


2020 ◽  
Vol 27 (1) ◽  
pp. 106-120 ◽  
Author(s):  
L. A. Rodionova ◽  
E. D. Kopnova

The relevance of the chosen topic is closely related to the development of a system for monitoring the implementation of the May Presidential Decree (2018) to increase life expectancy and improve the quality of life of the population. It has been stated that despite the positive dynamics of life expectancy over the past decade, Russia still has a huge regional differentiation (16,6 years for women, 18,2 years for men in 2016) and an average gender gap - 10,6 years. The choice of factors affecting the gender gap in life expectancy in Russian regions is supported by a conclusion most common in foreign studies that climatic conditions, living conditions, the quality of food and drinking water, alcohol consumption are essential components of public health and life expectancy.The article provides an overview of studies on assessment factors of life expectancy, presents the authors’ approach to identifying gender gaps in life expectancy, living conditions, and lifestyle affecting the indicator of life expectancy. The paper presents the results of a comparative analysis of gender gap in life expectancy in Russia and foreign countries. The paper studies the correlation between living conditions and lifestyle, and life expectancy.Classification of the regions by the life expectancy at birth for men and women is an important component of this study. The authors used Rosstat data for 2016 and the k-means method to select three clusters of Russian regions taking into account gender, living conditions and lifestyle. The paper identifies similar health problems of the regions that are associated with alcohol consumption, poor nutrition and poor quality of drinking water, poor housing and living conditions. The lowest life expectancy rates for men and women are recorded in regions of the 1st cluster (Jewish Autonomous Region, Republic of Tuva, Chukotka Autonomous Area). High mortality rates are a result of external causes. There is a poor quality of drinking water and poor nutrition, excessive alcohol consumption, and inadequate housing conditions.Based on the obtained results were determined possible reserves for reducing the gender and regional differentiation of life expectancy.


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