RESUMEN
The first British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS)-endorsed faecal microbiota transplant (FMT) guidelines were published in 2018. Over the past 5 years, there has been considerable growth in the evidence base (including publication of outcomes from large national FMT registries), necessitating an updated critical review of the literature and a second edition of the BSG/HIS FMT guidelines. These have been produced in accordance with National Institute for Health and Care Excellence-accredited methodology, thus have particular relevance for UK-based clinicians, but are intended to be of pertinence internationally. This second edition of the guidelines have been divided into recommendations, good practice points and recommendations against certain practices. With respect to FMT for Clostridioides difficile infection (CDI), key focus areas centred around timing of administration, increasing clinical experience of encapsulated FMT preparations and optimising donor screening. The latter topic is of particular relevance given the COVID-19 pandemic, and cases of patient morbidity and mortality resulting from FMT-related pathogen transmission. The guidelines also considered emergent literature on the use of FMT in non-CDI settings (including both gastrointestinal and non-gastrointestinal indications), reviewing relevant randomised controlled trials. Recommendations are provided regarding special areas (including compassionate FMT use), and considerations regarding the evolving landscape of FMT and microbiome therapeutics.
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Infecciones por Clostridium , Trasplante de Microbiota Fecal , Trasplante de Microbiota Fecal/métodos , Humanos , Infecciones por Clostridium/terapia , Reino Unido , Clostridioides difficile , COVID-19/terapia , Recurrencia , Gastroenterología/normas , Gastroenterología/métodos , SARS-CoV-2 , Sociedades MédicasRESUMEN
AIM: Restorative proctocolectomy has been widely adopted as the procedure of choice for restoring gastrointestinal continuity following proctocolectomy. It is often associated with improved quality of life and high patient satisfaction; however, the development of a pouch anal fistula can cause significant morbidity. Pouch fistulas are notoriously difficult to treat and there is great heterogeneity in the management reported of these fistulas. A lack of classification, and the assumption that fistulas originating from completely different aetiologies will behave and respond similarly to a particular treatment strategy, precludes meaningful comparison of management outcomes. We aim to introduce consistency in the reporting of pouch fistulas using a novel classification system. METHODS: A consensus process involving clinicians experienced in the management of pouch fistulas from two high volume tertiary centres was performed. RESULTS: We propose that pouch anal fistulas should be classified into four distinct groups according to their aetiology: group 1, anastomotic related; group 2, inflammatory bowel disease related, with sub-classifications Crohn's (type A) and non-Crohn's (type B) in origin; group 3, cryptoglandular related; and group 4, malignancy related. CONCLUSION: Classification of pouch fistulas according to their aetiology will provide consistency in the literature and improve the quality of prospective evidence for the management of pouch fistulas.
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Reservorios Cólicos , Proctocolectomía Restauradora , Fístula Rectal , Reservorios Cólicos/efectos adversos , Humanos , Proctocolectomía Restauradora/efectos adversos , Estudios Prospectivos , Calidad de Vida , Fístula Rectal/etiología , Fístula Rectal/cirugíaRESUMEN
BACKGROUND AND AIMS: Anti-tumour necrosis factor [anti-TNF] therapy is indicated for treatment of moderate to severe inflammatory bowel disease [IBD], but has a primary non-response rate of around 30%. We aim to use metabonomic and metataxonomic profiling to identify predictive biomarkers of anti-TNF response in Crohn's disease. METHODS: Patients with luminal Crohn's disease, commencing anti-TNF therapy, were recruited with urine, faeces, and serum samples being collected at baseline and 3-monthly. Primary response was defined according to a combination of clinical and objective markers of inflammation. Samples were measured using three UPLC-MS assays: lipid, bile acid, and Hydrophillic Interaction Liquid Chromatography [HILIC] profiling with 16S rRNA gene sequencing of faeces. RESULTS: Samples were collected from 76 Crohn's disease patients who were anti-TNF naïve and from 13 healthy controls. There were 11 responders, 37 non-responders, and 28 partial responders in anti-TNF-treated Crohn's patients. Histidine and cysteine were identified as biomarkers of response from polar metabolite profiling [HILIC] of serum and urine. Lipid profiling of serum and faeces found phosphocholines, ceramides, sphingomyelins, and triglycerides, and bile acid profiling identified primary bile acids to be associated with non-response to anti-TNF therapy, with higher levels of phase 2 conjugates in non-responders. Receiver operating curves for treatment response demonstrated 0.94 +/ -0.10 [faecal lipid], 0.81 +/- 0.17 [faecal bile acid], and 0.74 +/- 0.15 [serum bile acid] predictive ability for anti-TNF response in Crohn's disease. CONCLUSIONS: This prospective, longitudinal cohort study of metabonomic and 16S rRNA gene sequencing analysis demonstrates that a range of metabolic biomarkers involving lipid, bile acid, and amino acid pathways may contribute to prediction of response to anti-TNF therapy in Crohn's disease. PODCAST: This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast.
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Adalimumab , Ácidos y Sales Biliares/análisis , Enfermedad de Crohn , Cisteína/análisis , Histidina/análisis , Inflamación , Infliximab , Metabolismo de los Lípidos/efectos de los fármacos , ARN Ribosómico 16S/análisis , Adalimumab/administración & dosificación , Adalimumab/efectos adversos , Adulto , Biomarcadores Farmacológicos/análisis , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/epidemiología , Enfermedad de Crohn/inmunología , Heces , Femenino , Humanos , Inflamación/sangre , Inflamación/diagnóstico , Inflamación/orina , Infliximab/administración & dosificación , Infliximab/efectos adversos , Londres , Estudios Longitudinales , Masculino , Metabolómica/métodos , Valor Predictivo de las Pruebas , Inhibidores del Factor de Necrosis Tumoral/administración & dosificación , Inhibidores del Factor de Necrosis Tumoral/efectos adversosRESUMEN
INTRODUCTION: Restorative proctocolectomy is a surgical treatment for patients with medically refractory ulcerative colitis and some cases of familial adenomatous polyposis. Intestinal failure, defined as an inability to maintain adequate hydration and micronutrient balances when on a conventionally accepted normal diet, is a rare complication of restorative proctocolectomy. We describe our experience of patients with restorative proctocolectomy who have developed intestinal failure requiring parenteral support. MATERIAL AND METHODS: This was a retrospective analysis using a database of patients referred to our intestinal failure unit from January 1998 to January 2016. We analysed the records of all those patients who had restorative proctocolectomy who developed intestinal failure. RESULTS: 807 patient records analysed, 35 patients were found to have had a restorative proctocolectomy (13 male and 22 female). Ninety-one percent (n = 32) of patients developed IF as a consequence of unpredictable complications which occurred after RPC formation. Potentially predictable complications were noted in 9% (n = 3) of patients. DISCUSSION AND CONCLUSIONS: Most cases of intestinal failure in restorative proctocolectomy were unpredictable. In a small number of patients, accurate assessment and measurement of the small intestine may have better predicted the adverse outcome of intestinal failure allowing improved pre-operative counseling of patients.
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Reservorios Cólicos , Nutrición Parenteral en el Domicilio , Femenino , Humanos , Masculino , Proctocolectomía Restauradora , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
INTRODUCTION: Restorative proctocolectomy has gained acceptance in the surgical management of medically refractive ulcerative colitis and cancer prevention in familial adenomatous polyposis. Incontinence following restorative proctocolectomy occurs in up to 25% of patients overnight. The Renew® insert is an inert single-use device which acts as an anal plug. The aim of this study was to assess the acceptability, effectiveness and safety of the Renew® insert in patients who have undergone restorative proctocolectomy. The device has yet to be assessed in patients who have undergone restorative proctocolectomy. METHOD: This was a prospective study exploring the acceptability, effectiveness and safety of the Renew® insert in improving incontinence in patients who had undergone restorative proctocolectomy. A total of 15 patients with incontinence were asked to use the Renew® insert for 14 days following their standard care. The Incontinence Questionnaire-Bowels was used pre- and posttreatment to assess response and patients were asked to report the perceived acceptability, effectiveness and safety of the device at the end of the trial. RESULTS: The device was acceptable to 8/15 (53%) of patients and was effective in 6/15 (40%). Only 2/15 (13%) of patients raised any safety concerns, and these were minor. The device was associated with a significant reduction in night seepage (P = 0.034). CONCLUSION: In a small study, the Renew® insert can be both acceptable and effective and is also associated with few safety concerns. It is also associated with significant reductions in night-time seepage.
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Colitis Ulcerosa/cirugía , Equipos y Suministros , Incontinencia Fecal/terapia , Aceptación de la Atención de Salud , Complicaciones Posoperatorias/terapia , Proctocolectomía Restauradora , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Evidence from groups who have studied fistula aetiology and extrapolation from interventional studies supports a multifactorial hypothesis of Crohn's perianal fistula, with several pathophysiological elements that may contribute to fistula formation, persistence and resistance to treatment. AIM: An evidence synthesis of current understanding of pathophysiological factors underlying Crohn's perianal fistula is presented, exploring the fundamental reasons why some treatments succeed and others fail, as a means of focussing clinical knowledge on improving treatment of Crohn's perianal fistula. METHODS: Evidence to support this review was gathered via the Pubmed database. Studies discussing pathophysiological factors underpinning perianal fistula, particularly in Crohn's disease, were reviewed and cross-referenced for additional reports. RESULTS: Pathophysiological factors that impact on success or failure of interventions for Crohn's perianal fistulae include the high-pressure zone, obliterating the dead space, disconnecting the track from the anus, removing epithelialisation, eradicating sepsis and by-products of bacterial colonisation, correcting abnormalities in wound repair and removing the pro-inflammatory environment which allows fistula persistence. Most current interventions for Crohn's perianal fistulae tend to focus on a single, or at best two, aspects of the pathophysiology of Crohn's anal fistulae; as a result, failure to heal fully is common. CONCLUSIONS: For an intervention or combination of interventions to succeed, multiple factors must be addressed. We hypothesise that correct, timely and complete attention to all of these factors in a multimodal approach represents a new direction that may enable the creation of an effective treatment algorithm for Crohn's anal fistula.
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Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/terapia , Fístula Rectal/etiología , Fístula Rectal/terapia , Canal Anal/patología , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/epidemiología , Humanos , Pronóstico , Fístula Rectal/diagnóstico , Fístula Rectal/epidemiología , Factores de Riesgo , Resultado del TratamientoAsunto(s)
Enfermedad de Crohn , Factor de Necrosis Tumoral alfa , Adalimumab , Humanos , Infliximab , Medicina de PrecisiónRESUMEN
BACKGROUND: The resident gut microbiota is essential for physiological processes; the disturbance of its balance is linked to intestinal inflammation. The ileoanal pouch is a model for the study of intestinal inflammation, as inflammation of the pouch is common and mostly develops within 12 months following ileostomy closure. This allows the longitudinal study of the microbiota, giving insight into the microbiota changes during transition from a normal to an inflamed pouch. AIM: To explore the literature on the microbiota of the ileoanal pouch in health and disease. METHODS: A systematic computer search of the on-line bibliographic databases MEDLINE and EMBASE was performed between 1966 and February 2017. Randomised controlled trials, cohort studies and observational studies were included. Studies were included if they reported microbiota analysis on faecal samples or tissue from the ileoanal pouch. RESULTS: Twenty-six papers were eligible. Following ileostomy closure, anaerobic bacteria are the abundant species in the ileoanal pouch with presence of a diverse microbiota key to maintaining a healthy ileoanal pouch. Acute pouchitis is associated with an increase in Clostridia species, while chronic pouchitis is associated with an increase in Staphylococcus aureus. In the treatment of pouchitis, a decrease in Clostridia species appears to be associated with treatment response. CONCLUSION: The microbiota plays an important role in both the inflamed and the healthy ileoanal pouch. A direct causal relationship between individual microbiota changes and inflammation has not yet been established, but manipulation of the ileoanal pouch microbiota may be a novel therapeutic avenue to explore.
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Reservorios Cólicos/microbiología , Microbioma Gastrointestinal/fisiología , Salud , Reservoritis/microbiología , Adulto , Heces/microbiología , Femenino , Humanos , Estudios Longitudinales , Masculino , Reservoritis/etiologíaRESUMEN
International Federations in Paralympic sports should develop evidence-based classification, based on the relative strength of association between impairment and activities that determine sport-specific performance. The purpose of the current study was to assess the relationship between trunk strength impairment and three activities that determine performance in wheelchair rugby, and to determine whether this relationship supports the concept of "natural classes." Trunk muscle strength and three determinants of performance were assessed in 27 athletes. The correlations between lateral trunk muscle strength and the determinant tilting the chair, and between forward trunk muscle strength and the determinants 1 m acceleration and sprint momentum were calculated. To group athletes based on impairment, K-means cluster analysis was used to group athletes according to how much trunk muscle strength affected the activities. There were significant, moderate to strong correlations between left-right strength and chair tilting (r=.50), between forward strength and 1 m acceleration (r=.59), and between forward strength and sprint momentum (r=.79). Cluster analysis indicated at least one cut-point in performance with a decrease in impairment in all three wheelchair activities, supporting the concept of "natural classes."
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Rendimiento Atlético , Fuerza Muscular , Músculo Esquelético/fisiología , Torso/fisiopatología , Silla de Ruedas , Aceleración , Adulto , Atletas , Personas con Discapacidad , Fútbol Americano , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Treatment of inflammatory bowel disease (IBD) involves a multidisciplinary approach comprising medical management and sometimes surgery. Although diet is central to IBD management, the optimal diet for patients with IBD is uncertain. A UK collaborative partnership within the James Lind Alliance was set up between patients, clinicians and other stakeholders to develop research priorities in IBD. The aim of this short report is to provide a comprehensive summary of the research priority findings relating to diet in the treatment of IBD. METHODS: The James Lind Alliance Priority Setting Partnership process was used to develop research priorities in IBD. In brief, patients, clinicians and other stakeholders were invited to provide up to five treatment uncertainties in IBD. These uncertainties were collated, revised and ranked, leading to a final top 10 research questions in IBD. RESULTS: A total of 1671 uncertainties from 531 participants were collected and refined to exclude duplicates leaving 1253 uncertainties. Of these, 348 were categorised as diet-related and grouped according to topic. There were 206 uncertainties related to how diet can be used to treat IBD or alleviate symptoms. Seventy-two percent of diet-related questions came from patients. One broadly diet-related and two diet-specific treatment uncertainties were included in the top 10 research priorities for IBD. CONCLUSIONS: Dietary treatment options in the management of IBD are important research priorities. Almost three-quarters of diet related questions came from patients, who were particularly interested in how diet can impact disease activity and symptom control.
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Dieta , Enfermedades Inflamatorias del Intestino/dietoterapia , Suplementos Dietéticos , Manejo de la Enfermedad , Nutrición Enteral , Tracto Gastrointestinal/microbiología , Humanos , Micronutrientes/administración & dosificación , Probióticos/administración & dosificación , Encuestas y Cuestionarios , IncertidumbreRESUMEN
BACKGROUND: Faecal microbiota transplantation (FMT) is emerging as a novel therapy for ulcerative colitis (UC). Interpretation of efficacy of FMT for UC is complicated by differences among studies in blinding, FMT administration procedures, intensity of therapy and donor stool processing methods. AIM: To determine whether FMT is effective and safe for the induction of remission in active UC. METHODS: Medline (Ovid), Embase and the Cochrane Library were searched from inception through February 2017. Original studies reporting remission rates following FMT for active UC were included. All study designs were included in the systematic review and a meta-analysis performed including only randomised controlled trials (RCTs). RESULTS: There were 14 cohort studies and four RCTs that used markedly different protocols. In the meta-analysis of RCTs, clinical remission was achieved in 39 of 140 (28%) patients in the donor FMT groups compared with 13 of 137 (9%) patients in the placebo groups; odds ratio 3.67 (95% CI: 1.82-7.39, P<.01). Clinical response was achieved in 69 of 140 (49%) donor FMT patients compared to 38 of 137 (28%) placebo patients; odds ratio 2.48 (95% CI: 1.18-5.21, P=.02). In cohort studies, 39 of 168 (24%; 95% CI: 11%-40%) achieved clinical remission. CONCLUSIONS: Despite variation in processes, FMT appears to be effective for induction of remission in UC, with no major short-term safety signals. Further studies are needed to better define dose frequency and preparation methods, and to explore its feasibility, efficacy and safety as a maintenance agent.
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Colitis Ulcerosa/terapia , Trasplante de Microbiota Fecal/métodos , Heces , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Inducción de RemisiónRESUMEN
AIM: Chronic peri-pouch sepsis (CPPS) may be mistaken for antibiotic-dependent or refractory primary idiopathic pouchitis (ADRP), but requires different treatment such as drainage. The study aimed to identify the prevalence of CPPS in patients thought to have ADRP. The secondary aims were to identify any specific features on pouchoscopy suggesting CPPS and to determine the results of treatment for CPPS. METHOD: The records of patients who had been treated for ADRP between March 2006 and June 2015 were reviewed retrospectively. Only those with endoscopic evidence of pouch inflammation who had also undergone MRI of the pelvis were included. The findings on pouchoscopy and the outcome of treatment were determined. RESULTS: Sixty-eight patients (43 men, 63%) were identified with apparent ADRP between March 2006 and June 2015. MRI of the pelvis showed CPPS in 26 (38%). In those with CPPS, the inflammation was more often located in the upper pouch alone (15%) compared with patients without CPPS (0%) (P = 0.0184). Examination under anaesthesia was performed in 13 of those with CPPS. In five a collection was identified and drained; symptoms improved in only one (4%). Eighteen patients (69%) remained on antibiotics and seven (27%) had a defunctioning stoma or underwent pouch excision. CONCLUSION: In patients thought to have ADRP, 38% had CPPS on MRI. There was no clinically relevant specific feature on pouchoscopy suggestive of CPPS. The possibility of CPPS should be considered early in patients with apparent ADRP and pelvic MRI performed. This might lead to earlier detection of CPPS and appropriate treatment.
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Reservorios Cólicos/efectos adversos , Reservoritis/complicaciones , Sepsis/epidemiología , Adolescente , Adulto , Antibacterianos/uso terapéutico , Enfermedad Crónica , Endoscopía Gastrointestinal/métodos , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pelvis/diagnóstico por imagen , Reservoritis/diagnóstico por imagen , Reservoritis/tratamiento farmacológico , Reservoritis/etiología , Prevalencia , Proctocolectomía Restauradora/efectos adversos , Proctocolectomía Restauradora/métodos , Estudios Retrospectivos , Sepsis/etiología , Adulto JovenRESUMEN
In Paralympic sport, classification of impairment is needed to prevent a one-sided and predictable outcome of competition, in which the least impaired athlete has the best chance to win. To develop evidence-based classification in wheelchair rugby, the impact of trunk impairment, measured by the Trunk Impairment Classification (TIC), on performance-determining activities was assessed. Arm impairment was analyzed as a covariant. Fifty-five athletes, 21 with TIC score 0, 13 with TIC score 0.5, 11 with TIC score 1.0, and 10 with TIC score 1.5 performed standardized sport-specific activities. A multiple step forward regression analysis was performed for all activities to assess the relative impact of trunk and arm impairment on performance. Trunk impairment was the most important factor for tilting the chair and acceleration in the first 2 m. The explained variance of the performance by trunk and arm impairment ranged from 23% for acceleration in the first meter, to 37% for sprint momentum, the tilt test left, and the time to cover 3 and 4 m. This study shows that athletes with limited trunk impairment are more proficient in wheelchair rugby than athletes with severe trunk impairment.
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Atletas/clasificación , Evaluación de la Discapacidad , Personas con Discapacidad/clasificación , Fútbol Americano , Torso/fisiopatología , Silla de Ruedas , Aceleración , Adolescente , Adulto , Humanos , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: Restorative proctocolectomy with ileal pouch anal anastomosis (IPAA) is considered the procedure of choice in patients with ulcerative colitis (UC) refractory to medical therapy. The incidence of pouchitis is 40% at 5 years. Ten to 15% of patients with pouchitis experience chronic pouchitis. AIM: To determine the efficacy of medical therapies for the treatment of chronic refractory pouchitis in patients undergoing IPAA for UC. METHODS: A systematic computer-assisted search of the on-line bibliographic database MEDLINE and EMBASE was performed between 1966 and February 2016. All original studies reporting remission rates following medical treatment for chronic pouchitis were included. All study designs were considered. Remission was defined according to the individual study. Remission endpoints ranged from 15 days to 10 weeks. Chronic pouchitis was defined by each study. RESULTS: Twenty-one papers were considered eligible. Results from all studies combined suggested that overall remission was obtained in 59% of patients (95% CI: 44-73%). Antibiotics significantly induced remission in patients with chronic pouchitis with 74% remission rate (95% CI:56-93%), (P < 0.001). Biologics significantly induced remission in patients with chronic pouchitis with 53% remission rate (95% CI:30-76%), (P < 0.001). Steroids, bismuth, elemental diet and tacrolimus all can induce remission but failed to achieve significance. Faecal microbiota transplantation in a single study was not found to achieve remission. CONCLUSIONS: Treatment of chronic refractory pouchitis remains difficult and is largely empirical. Larger randomised controlled trials will help aid the management of chronic pouchitis.
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Colitis Ulcerosa/cirugía , Reservoritis/terapia , Proctocolectomía Restauradora/efectos adversos , Algoritmos , Canal Anal/cirugía , Reservorios Cólicos , Humanos , Reservoritis/etiología , Inducción de Remisión , Tacrolimus/administración & dosificaciónRESUMEN
BACKGROUND: Temporary faecal diversion is sometimes used for management of refractory perianal Crohn's disease (CD) with variable success. AIMS: To perform a systematic review with meta-analysis to evaluate the effectiveness, long-term outcomes and factors associated with success of temporary faecal diversion for perianal CD. METHODS: Through a systematic literature review through 15 July 2015, we identified 16 cohort studies (556 patients) reporting outcomes after temporary faecal diversion. We estimated pooled rates [with 95% confidence interval (CI)] of early clinical response, attempted and successful restoration of bowel continuity after temporary faecal diversion (without symptomatic relapse), and rates of re-diversion (in patients with attempted restoration) and proctectomy (with or without colectomy and end-ileostomy). We identified factors associated with successful restoration of bowel continuity. RESULTS: On meta-analysis, 63.8% (95% CI: 54.1-72.5) of patients had early clinical response after faecal diversion for refractory perianal CD. Restoration of bowel continuity was attempted in 34.5% (95% CI: 27.0-42.8) of patients, and was successful in only 16.6% (95% CI: 11.8-22.9). Of those in whom restoration was attempted, 26.5% (95% CI: 14.1-44.2) required re-diversion because of severe relapse. Overall, 41.6% (95% CI: 32.6-51.2) of patients required proctectomy after failure of temporary faecal diversion. There was no difference in the successful restoration of bowel continuity after temporary faecal diversion in the pre-biological or biological era (13.7% vs. 17.6%, P = 0.60), in part due to selection bias. Absence of rectal involvement was the most consistent factor associated with restoration of bowel continuity. CONCLUSIONS: Temporary faecal diversion may improve symptoms in approximately two-thirds of patients with refractory perianal Crohn's disease, but bowel restoration is successful in only 17% of patients.
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Enfermedades del Ano/cirugía , Enfermedad de Crohn/cirugía , Ileostomía , Enfermedades del Ano/epidemiología , Enfermedades del Ano/patología , Colectomía/efectos adversos , Colectomía/estadística & datos numéricos , Enfermedad de Crohn/epidemiología , Enfermedad de Crohn/patología , Heces , Humanos , Ileostomía/efectos adversos , Ileostomía/métodos , Ileostomía/rehabilitación , Ileostomía/estadística & datos numéricos , Proctocolectomía Restauradora/estadística & datos numéricos , RecurrenciaRESUMEN
Faecal microbiota transplantation (FMT) is effective in the treatment of Clostridium difficile infection, where efficacy correlates with changes in microbiota diversity and composition. The effects of FMT on recipient microbiota in inflammatory bowel diseases (IBD) remain unclear. We assessed the effects of FMT on microbiota composition and function, mucosal immune response, and clinical outcome in patients with chronic pouchitis. Eight patients with chronic pouchitis (current PDAI ≥7) were treated with FMT via nasogastric administration. Clinical activity was assessed before and four weeks following FMT. Faecal coliform antibiotic sensitivities were analysed, and changes in pouch faecal and mucosal microbiota assessed by 16S rRNA gene pyrosequencing and (1)H NMR spectroscopy. Lamina propria dendritic cell phenotype and cytokine profiles were assessed by flow cytometric analysis and multiplex assay. Following FMT, there were variable shifts in faecal and mucosal microbiota composition and, in some patients, changes in proportional abundance of species suggestive of a "healthier" pouch microbiota. However, there were no significant FMT-induced metabolic or immunological changes, or beneficial clinical response. Given the lack of clinical response following FMT via a single nasogastric administration our results suggest that FMT/bacteriotherapy for pouchitis patients requires further optimisation.
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Trasplante de Microbiota Fecal , Reservoritis/terapia , Adulto , Enfermedad Crónica , Femenino , Humanos , Inmunidad Innata , Masculino , Metabolómica , Persona de Mediana Edad , Reservoritis/inmunología , Reservoritis/metabolismo , Reservoritis/microbiología , Espectroscopía de Protones por Resonancia MagnéticaRESUMEN
AIM: The aetiology of Crohn's disease-related anal fistula remains obscure. Microbiological, genetic and immunological factors are thought to play a role but are not well understood. The microbiota within anal fistula tracts has never been examined using molecular techniques. The present study aimed to characterize the microbiota in the tracts of patients with Crohn's and idiopathic anal fistula. METHOD: Samples from the fistula tract and rectum of patients with Crohn's and idiopathic anal fistula were analysed using fluorescent in situ hybridization, Gram staining and scanning electron microscopy were performed to identify and quantify the bacteria present. RESULTS: Fifty-one patients, including 20 with Crohn's anal fistula, 18 with idiopathic anal fistula and 13 with luminal Crohn's disease and no anal fistula, were recruited. Bacteria were not found in close association with the luminal surface of any of the anal fistula tracts. CONCLUSION: Anal fistula tracts generally do not harbour high levels of mucosa-associated microbiota. Crohn's anal fistulas do not seem to harbour specific bacteria. Alternative explanations for the persistence of anal fistula are needed.
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Enfermedad de Crohn/complicaciones , Fístula Rectal/microbiología , Adulto , Canal Anal/microbiología , Enfermedad de Crohn/microbiología , Femenino , Humanos , Mucosa Intestinal/microbiología , Masculino , Microbiota , Persona de Mediana EdadRESUMEN
Inflammatory bowel disease (IBD) is increasing in incidence in both the developed and the developing world. Genetic, immunological and environmental factors are known to be involved. Genome-wide studies have examined the contribution played by host genetics in the development of IBD and have estimated that genetic factors are responsible for about 25 % of the disease risk. Having an IBD-associated genotype does not always lead to development of the disease phenotype, and hence it seems likely that environmental factors are key to triggering development of the disease in genetically susceptible individuals. The gut microbiota contains more cells than its human host, and mounting evidence attests to the importance of the microbiota in the development of several diseases, including IBD, metabolic syndrome and CVD. The present paper reviews the interplay between the microbiota and the mucosal immune system in health and in IBD; and discusses the evidence base for the use of therapeutic modulation of the microbiota to prevent and treat IBD.
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Tracto Gastrointestinal/microbiología , Enfermedades Inflamatorias del Intestino/microbiología , Enfermedades Inflamatorias del Intestino/terapia , Microbiota , Antibacterianos/farmacología , Predisposición Genética a la Enfermedad , Humanos , Enfermedades Inflamatorias del Intestino/genética , Fenotipo , Prebióticos , Probióticos/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: The management of perianal Crohn's fistulas represents a significant challenge. A combination of medical and surgical therapy, guided by radiology, is often required. AIM: To review systematically the literature to assess fistula healing rates with medical treatment (anti-TNF-α therapies ± immunomodulators) or surgical treatment alone, compared with combined medical and surgical treatment in fistulising perianal Crohn's disease (CD). METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used. Two independent reviewers searched the literature. RESULTS: Twenty-four articles were included. The total population was 1139 patients; 460 (40%) received single treatment with either medical or surgical therapy, and 679 (60%) received combined medical and surgical therapy. Eight studies compared single and combination therapy, with a total population of 797 patients (single therapy: n = 448, combination therapy: n = 349). In the single therapy group, 191/448 were in complete remission (43%). This was lower than the healing rate of the combination therapy group 180/349 (52%). No response to therapy was noted in 34% (153/448) of the single therapy group compared with 23% (80/349) of the combination group. CONCLUSIONS: Combined surgical and medical (anti-TNF-α ± immunomodulators) therapy may have additional beneficial effects on perianal fistula healing in patients with Crohn's disease, compared with surgery or medical therapy alone. A well-designed Crohn's perianal fistula clinical trial is required in a multidisciplinary medical and surgical setting, with clearly defined end points of clinical (and likely patient reported outcomes) and radiological healing.