Publications by authors named "Michael A Kamm"

171 Publications

Approach to Dietary Restriction in Irritable Bowel Syndrome.

Clin Gastroenterol Hepatol 2021 Aug 5. Epub 2021 Aug 5.

The University of Melbourne, Melbourne, Victoria, Australia; Department of Gastroenterology, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia.

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http://dx.doi.org/10.1016/j.cgh.2021.08.004DOI Listing
August 2021

Endoscopic Prediction of Crohn's Disease Postoperative Recurrence.

Inflamm Bowel Dis 2021 Jul 7. Epub 2021 Jul 7.

Department of Gastroenterology, St. Vincent's Hospital and Department of Medicine, The University of Melbourne, Melbourne, Australia.

Background: The presence and severity of endoscopic recurrence after Crohn's disease intestinal resection predicts subsequent disease course. The Rutgeerts postoperative endoscopic recurrence score is unvalidated but has proven prognostically useful in many clinical studies. This study aimed to investigate the association between specific early endoscopic findings and subsequent disease course.

Methods: In the setting of a randomized controlled trial (the POCER study), 85 patients underwent colonoscopy at 6 and 18 months after intestinal resection. Patients received 3 months of metronidazole, and high-risk patients received a thiopurine (or adalimumab if they were thiopurine intolerant). For endoscopic recurrence (Rutgeerts score ≥i2) at 6 months, patients stepped up to a thiopurine, fortnightly adalimumab with thiopurine, or weekly adalimumab. Central readers confirmed Rutgeerts, Simple Endoscopic Score for Crohn's Disease, Crohn's Disease Endoscopic Index of Severity scores, and 5 newly tested endoscopic parameters: anastomotic ulcer depth (superficial vs deep), number of ulcers (0, ≤2, >2), ulcer size (1-5 mm, ≥6 mm), circumferential extent of ulceration (<25%, ≥25%), and the presence or absence of stenosis. The POCER index, based on the 6-month postoperative findings, was then developed in relation to predicting the endoscopic outcome at 18 months.

Results: Of the 5 parameters, the combination of ulcer depth and circumference at the anastomosis at 6 months was associated with endoscopic recurrence at 18 months (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.03-2.50; P = 0.035) with an area under the receiver operating characteristic curve of 0.62 (95% CI, 0.5-0.75). The combination of these 2 parameters formed the basis of the POCER index (range, 0-4 with 0 denoting no ulcers and 4 denoting deep ulceration with >25% circumferential involvement). The new index had a strong correlation with the Rutgeerts score measured at the same time points: Spearmans' r = .80 at 6 months and r = .77 at 18 months (P < 0.001 at both time points). A POCER index of ≥2 and a Rutgeerts score of ≥i2 both had a sensitivity of 0.41 for recurrence; however, the POCER index had a higher specificity (0.8 and 0.67, respectively). The POCER index at 6 months was associated with endoscopic recurrence at 18 months (OR, 1.5; 95% CI, 1.2-2.0; P = 0.002; area under the receiver operating characteristic curve of 0.70; 95% CI, 0.57-0.82), but the Rutgeerts score was not (OR, 1.2; 95% CI, 0.8-1.8; P = 0.402).

Conclusions: The POCER postoperative index comprises 2 key endoscopic factors related to the anastomosis that are associated with subsequent disease progression. A higher score, comprising the adverse prognostic factors of deep or circumferentially extensive anastomotic ulceration, may help identify patients who require more intensive therapy.
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http://dx.doi.org/10.1093/ibd/izab134DOI Listing
July 2021

Fecal microbiota transplantation therapy in Crohn's disease: Systematic review.

J Gastroenterol Hepatol 2021 Jun 24. Epub 2021 Jun 24.

Department of Gastroenterology, St Vincent's Hospital, Melbourne, Victoria, Australia.

Background: The gastrointestinal microbiota is the key antigenic drive in the inflammatory bowel diseases. Randomized controlled trials (RCTs) in ulcerative colitis have established fecal microbiota transplantation (FMT) as an effective therapy. We have conducted a systematic review to evaluate the efficacy of FMT in Crohn's disease.

Methods: A systematic literature search was performed through to August 2020 (MEDLINE; Embase). Studies were included if they reported FMT administration in patients with Crohn's disease, and reported on clinical outcomes.

Results: Fifteen studies published between 2014 and 2020, comprising 13 cohort studies and two RCTs, were included in the analysis. The majority of trials evaluated FMT for induction of remission, with follow-up duration varying from 4 to 52 weeks. One RCT in 21 patients, of single-dose FMT versus placebo, following steroid-induced remission, showed a higher rate of steroid-free clinical remission in the FMT group compared to the control group: 87.5% vs 44.4% at week 10 (P = 0.23). Another RCT, two-dose FMT in 31 patients, showed an overall clinical remission rate of 36% at week 8, however, with no difference in clinical or endoscopic endpoints between FMT administered by gastroscopy and colonoscopy. Considering all studies, the clinical response rates in early follow up were higher following multiple FMT than with single FMT. FMT dose did not appear to influence clinical outcomes, nor did whether FMT was fresh or frozen. FMT delivered via upper gastrointestinal route demonstrated higher early efficacy rates of 75 to 100% compared with lower delivery route rates of 30% to 58%, but on follow up beyond 8 weeks, this difference was not maintained. Whether pre-FMT antibiotic administration was beneficial was not able to be determined due to the limited number of patients receiving antibiotics and varying antibiotic regimens. No serious adverse events were reported.

Conclusions: Preliminary studies suggest that FMT may be an effective therapy in Crohn's disease. However large controlled trials are needed. No serious safety concerns have been identified.
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http://dx.doi.org/10.1111/jgh.15598DOI Listing
June 2021

Systematic review: efficacy of escalated maintenance anti-tumour necrosis factor therapy in Crohn's disease.

Aliment Pharmacol Ther 2021 08 21;54(3):249-266. Epub 2021 Jun 21.

Faculty of Medicine, Dentistry and Health Sciences, Melbourne Medical School, The University of Melbourne, Melbourne, Vic., Australia.

Background: Loss of response to anti-TNF agents is a common clinical problem. Dose escalation may be effective for reestablishing clinical response in Crohn's disease (CD).

Aims: To perform a systematic review assessing the efficacy of escalated maintenance anti-TNF therapy in CD.

Methods: EMBASE, MEDLINE, Web of Science, and CENTRAL databases were searched for English language publications through to April 25, 2021. Full-text articles evaluating escalated maintenance treatment (infliximab or adalimumab) in adult CD patients were included.

Results: A total of 4733 records were identified, and 68 articles met eligibility criteria. Rates of clinical response (33%-100%) and remission (15%-83%) after empiric dose escalation for loss of response to standard anti-TNF therapy were high but varied across studies. Dose intensification strategies (doubling the dose versus shortening the therapeutic interval) were similarly efficacious. Dose-escalated patients tended to have higher serum drug levels compared to those on standard dosing. An exposure-response relationship following dose escalation was found in a number of observational studies. Randomised controlled trials comparing therapeutic drug monitoring (TDM) to empiric treatment intensification have failed to reach their primary end-points. Strategies including Bayesian dashboard-dosing and early treatment escalation targeting biomarker normalisation were found to be associated with improved long-term outcomes.

Conclusions: Empiric escalation of maintenance anti-TNF therapy can recapture clinical response in a majority of patients with secondary loss of response to standard maintenance doses. Proactive optimisation of maintenance dosing might prolong time to loss of response in some patients.
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http://dx.doi.org/10.1111/apt.16479DOI Listing
August 2021

A Single Educational Intervention Improves Pregnancy-Related Knowledge and Emotional Health Among Women With IBD Who Are Pregnant or Wish to Conceive.

Inflamm Bowel Dis 2021 Mar 11. Epub 2021 Mar 11.

Department of Gastroenterology, St. Vincent's Hospital, Melbourne, Australia.

Background: There is considerable interest in improving the education and care of women with inflammatory bowel disease (IBD) to improve pregnancy outcomes. Despite increased awareness, not all women with IBD have access to pregnancy-related education and the quality of counseling is variable. We aimed to assess the effectiveness of a simple educational intervention for improving pregnancy-related knowledge and to evaluate the effect of education on patient outcomes including anxiety, depression, and quality of life in women with IBD.

Methods: This prospective study of women with IBD who were pregnant or planning a pregnancy evaluated the effectiveness of a single gastroenterologist-led educational intervention in improving pregnancy-related knowledge, measured using the Crohn's and Colitis Pregnancy Knowledge score 1 month postintervention. Secondary outcomes included the effect on anxiety and depression, quality of life, medication adherence, and patient satisfaction.

Results: One hundred women with IBD were recruited. Fifty percent were pregnant at the time of the intervention. Baseline knowledge scores were similar independent of the patients' pregnancy status or whether they had previously received counseling from their gastroenterologist. Median Crohn's and Colitis Pregnancy Knowledge scores postintervention (n = 82) were higher than preintervention scores (14/17 vs 10/17; P < 0.001). In addition, 32% of patients had poor knowledge at baseline (score ≤7/17), compared to only 5% after the intervention (P < 0.001). There was a significant improvement in total anxiety and depression and quality of life scores postintervention. Medication adherence and patient satisfaction were excellent.

Conclusions: Uptake of this gastroenterologist-led educational intervention has the potential to improve pregnancy knowledge, promote medication adherence, and enhance quality of life for women with IBD globally.
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http://dx.doi.org/10.1093/ibd/izab021DOI Listing
March 2021

Maternal thiopurine metabolism during pregnancy in inflammatory bowel disease and clearance of thiopurine metabolites and outcomes in exposed neonates.

Aliment Pharmacol Ther 2021 04 19;53(7):810-820. Epub 2021 Feb 19.

Melbourne, Vic., Australia.

Background: Azathioprine and mercaptopurine are considered safe during pregnancy. However, the pharmacokinetic effects of pregnancy on thiopurine metabolism are undefined.

Aims: To characterise thiopurine metabolism in pregnancy and measure infant metabolite levels and outcomes.

Methods: Women with IBD who were taking a thiopurine and pregnant or trying to conceive were recruited. Maternal thiopurine metabolites were measured pre-conception, in each trimester, at delivery and post-partum. Infant metabolite levels, full blood examination and liver function testing were performed at birth, and repeated until levels undetectable and haematological and biochemical abnormalities resolved.

Results: Forty patients were included with measurements on at least two occasions, and two with only mother-baby levels at delivery. The median maternal 6-TGN level dropped in the second trimester compared with post-partum (179.0 vs 323.5 pmol/8 × 10 RBCs, P < 0.001) and the median 6-MMP level increased in the second trimester compared with post-partum (1103.0 vs 329.5 pmol/8 × 10 RBCs, P < 0.01). At delivery, the median 6-TGN level was lower in infants (n = 20) than mothers (78.5 vs 217 pmol/8 × 10 RBCs) (P < 0.001). Metabolites were not detected at 6 weeks in any infants. Anaemia was not seen, but thrombocytosis and abnormal liver biochemistry were detected in 80% of infants from 6 weeks, which gradually improved.

Conclusions: 6-TGN levels decrease and 6-MMP levels increase in the second trimester of pregnancy. Infants are exposed to thiopurine metabolites at low levels with clearance by 6 weeks and no anaemia. The cause of infant thrombocytosis and abnormal liver biochemistry in the absence of metabolites is unclear.
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http://dx.doi.org/10.1111/apt.16294DOI Listing
April 2021

Long-term outcomes of perianal fistulizing Crohn's disease in the biologic era.

JGH Open 2021 Feb 20;5(2):235-241. Epub 2020 Dec 20.

Department of Gastroenterology St Vincent's Hospital Melbourne Victoria Australia.

Background And Aim: While the advent of biologic therapy has led to improved outcomes in perianal fistulizing Crohn's disease (pfCD), loss of response is common. Previous studies suggest that patients who achieve radiological healing (with healing of underlying tracts on magnetic resonance imaging [MRI]) have a longer duration of response. The aim of this study was to characterize MRI outcomes of pfCD at a specialist inflammatory bowel disease (IBD) unit and compare the long-term clinical outcomes between patients achieving MRI and clinical healing.

Methods: A retrospective analysis of perianal fistulizing Crohn's patients treated at one specialist IBD unit was performed. Records were reviewed for patient demographics, disease history, clinical assessments, investigation results, and disease flares. Clinical remission was defined as closure of all baseline fistula openings. Radiological healing was defined as the absence of any T2-hyperintense sinuses, tracts, or collections. The primary end-point was rate of MRI healing. The secondary outcome was defined as flare-free period (time between clinical or radiological healing and patients' first signs/symptoms requiring therapy escalation).

Results: A total of 93 patients were included, with a median follow-up of 4.8 years (interquartile range, 2.4-6 years). Of 44 patients, 22 (50%) achieved clinical remission, while 15 of 93 (16%) achieved radiological healing. Of 22 patients, 10 (45%) with clinical remission had a subsequent disease flare (median time of 7 months) compared with 3 of 15 (20%) patients with MRI healing (median time of 3.6 years). Radiological healing was associated with a significantly longer flare-free period ( = 0.01).

Conclusion: Radiological healing occurs less commonly but represents a deeper form of healing, associated with improved long-term clinical outcomes.
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http://dx.doi.org/10.1002/jgh3.12475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857282PMC
February 2021

Determinants of long-term function and general well-being in patients with an ileoanal pouch.

JGH Open 2021 Jan 12;5(1):91-98. Epub 2020 Nov 12.

Department of Gastroenterology St Vincent's Hospital Melbourne Victoria Australia.

Background And Aim: Fecal incontinence and/or evacuation difficulty are common after ileoanal pouch surgery. This study aimed to determine whether the development of these symptoms can be predicted so that preventive measures might be instituted.

Methods: A consecutive series of 46 patients with ulcerative colitis (median age at surgery, 41 years; 50% female) and a functioning pouch for a duration ≥12 months was included. Assessment utilized medical record review and questionnaires on pre- and postoperative bowel function, quality of life, and psychological well-being. Pouch function was assessed by the Colorectal Functional Outcome score (0 = no impairment, 100 = worst impairment). Good pouch function was defined as a score ≤24.

Results: Fecal incontinence occurred in 67% preoperatively and 54% postoperatively; evacuation difficulty occurred in 65% and preoperatively and 85% postoperatively. The postoperative median Colorectal Functional Outcome score was 20 (range 2-74), with 44% of patients >24 (poor pouch function). Preoperative nocturnal fecal incontinence (odds ratio [OR] 4.92, 95% confidence interval [CI] 1.2-19.4, = 0.02) and pouchitis (OR 5.41, 95% CI 1.2-23.7, = 0.02) were associated with poor pouch function after multivariable regression analysis. Postoperative satisfaction, psychological well-being, and quality of life were significantly better in those with good pouch function, while poor sleep, impaired work, and sexual dysfunction were independently associated with poor pouch function.

Conclusions: Functional bowel symptoms are common before and after pouch surgery and are associated with the impairment of patient-reported outcomes. Preoperative nocturnal fecal incontinence predicts poor pouch function. Therapeutic focus on continence, bowel evacuation, psychological well-being, and quality of life should begin before surgery.
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http://dx.doi.org/10.1002/jgh3.12452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812478PMC
January 2021

Efficacy of drug and endoscopic treatment of Crohn's disease strictures: A systematic review.

J Gastroenterol Hepatol 2021 Feb 27;36(2):344-361. Epub 2020 Dec 27.

Department of Gastroenterology, St Vincent's Hospital, Fitzroy, Victoria, Australia.

Background And Aims: Strictures are the commonest complication in Crohn's disease. Surgery and endoscopic dilation are the mainstays of treatment, while drug therapy has often been considered contraindicated. The benefit of nonsurgical treatments, particularly drug and endoscopic therapy, need to be defined.

Methods: Ovid MEDLINE, Embase, Emcare, PsycINFO, CINAHL and the Cochrane Library (inception until August 30, 2019) were searched. Studies with ≥ 10 patients with Crohn's disease strictures, reporting on outcomes following medication or endoscopic treatment, were included.

Results: Of 3480 records, 85 studies met inclusion criteria and formed the basis of this analysis. Twenty-five studies assessed drug therapy; none were randomized trials. Despite study heterogeneity anti-tumor necrosis factor (TNF) therapy appeared effective, with 50% of patients avoiding surgery after 4 years of follow up. No other drug therapy was of demonstrable benefit. Sixty studies assessed endoscopic therapy including 56 on endoscopic balloon dilation, two assessed needle knife stricturotomy, and two stent insertion. Dilation was equally effective for de novo and anastomotic strictures ≤ 5 cm in length, with most studies reporting a subsequent surgical rate of 30% to 50%. Repeat dilation was required in approximately half of all patients.

Conclusions: Anti-TNF drug therapy and endoscopic balloon dilation are effective strategies for avoiding surgery in patients with stricturing Crohn's disease. Additional endoscopic therapies require further evaluation. Early data suggest that combining these therapies may provide greater benefit than individual therapies. Optimization of current drug and endoscopic therapy, and the incorporation of newer therapies, are needed for stricturing Crohn's disease.
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http://dx.doi.org/10.1111/jgh.15330DOI Listing
February 2021

Elucidation of Proteus mirabilis as a Key Bacterium in Crohn's Disease Inflammation.

Gastroenterology 2021 01 2;160(1):317-330.e11. Epub 2020 Oct 2.

Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China; Center for Gut Microbiota Research, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China. Electronic address:

Background & Aims: Proteus spp, Gram-negative facultative anaerobic bacilli, have recently been associated with Crohn's disease (CD) recurrence after intestinal resection. We investigated the genomic and functional role of Proteus as a gut pathogen in CD.

Methods: Proteus spp abundance was assessed by ure gene-specific polymerase chain in 54 pairs of fecal samples and 101 intestinal biopsies from patients with CD and healthy controls. The adherence, invasion, and intracellular presence of 2 distinct isolates of Proteus mirabilis in epithelial cells were evaluated using immunofluorescence and electron microscopy. Intracellular gene expression profiles and regulated pathways were analyzed by RNA sequencing and KEGG pathway analysis. Biologic functions of 2 isolates of P mirabilis were determined by in vitro cell culture, and in vivo using conventional mice and germ-free mice.

Results: Proteus spp were significantly more prevalent and abundant in fecal samples and colonic tissue of patients with CD than controls. A greater abundance of the genus Fusobacterium and a lesser abundance of the genus Faecalibacterium were seen in patients with CD with a high Proteus spp abundance. All 24 Proteus monoclones isolated from patients with CD belonged to members of P mirabilis lineages and 2 isolates, recovered from stool or mucosa, were used in further studies. Mice gavaged with either P mirabilis strain had more severe colonic inflammation. Co-culture of the isolates with epithelial cell lines showed bacterial adherence, invasion, increased production of pro-inflammatory cytokines IL-18 and IL-1α, and cell necrosis. Both isolates induced key pro-inflammatory pathways, including NOD-like receptor signaling, Jak-STAT signaling, and MAPK signaling, and induced pro-inflammatory genes and activated inflammation-related pathways in gnotobiotic mice.

Conclusions: P mirabilis in the gut is associated with CD and can induce inflammation in cells and animal models of colitis. P mirabilis can act as a pathobiont and play a crucial role in the pathogenesis of CD.
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http://dx.doi.org/10.1053/j.gastro.2020.09.036DOI Listing
January 2021

Infliximab, adalimumab and vedolizumab concentrations across pregnancy and vedolizumab concentrations in infants following intrauterine exposure.

Aliment Pharmacol Ther 2020 11 27;52(10):1551-1562. Epub 2020 Sep 27.

Fitzroy, VIC, Australia.

Background: The impact of pregnancy on levels of biologic agents in patients with IBD is undefined and time to elimination in vedolizumab-exposed infants is unknown.

Aims: To determine the effect of pregnancy on infliximab, adalimumab and vedolizumab levels and to study infant vedolizumab clearance METHODS: In a prospective observational study, maternal drug levels were measured pre-conception, in each trimester, at delivery and postpartum. The association between drug levels and gestation in weeks was assessed using generalised estimating equation modelling. Infant vedolizumab levels were performed at birth (cord blood), 6 weeks and 3 months or until undetectable.

Results: We included 50 IBD patients (23 on infliximab, 15 on adalimumab and 12 on vedolizumab) with at least two intrapartum observations, plus 5 patients on vedolizumab with only mother and baby samples at delivery. Modelling showed no change in adalimumab levels, an increase in infliximab levels of 0.16 (95% CI 0.08-0.24) µg/L/week (P < 0.001) and a decrease of 0.18 (95% CI: -0.33 to -0.02) µg/L/week (P = 0.03) for vedolizumab. In 17 mother-baby pairs, median infant vedolizumab levels at birth were lower than maternal levels (P < 0.05) with an infant:maternal ratio of 0.7 (IQR 0.5-0.9). Vedolizumab was undetectable between 15 and 16 weeks of age in all 12 infants completing follow-up testing.

Conclusions: During pregnancy, adalimumab levels remain stable, while infliximab levels increase and vedolizumab levels decrease. However, the increments were small suggesting that intrapartum therapeutic drug monitoring and dose adjustment are not indicated. Unlike infliximab and adalimumab, infant vedolizumab levels are lower in cord blood than in mothers and appear to clear rapidly.
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http://dx.doi.org/10.1111/apt.16102DOI Listing
November 2020

Defined microbiota transplant restores Th17/RORγt regulatory T cell balance in mice colonized with inflammatory bowel disease microbiotas.

Proc Natl Acad Sci U S A 2020 09 18;117(35):21536-21545. Epub 2020 Aug 18.

The Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029;

The building evidence for the contribution of microbiota to human disease has spurred an effort to develop therapies that target the gut microbiota. This is particularly evident in inflammatory bowel diseases (IBDs), where clinical trials of fecal microbiota transplantation have shown some efficacy. To aid the development of novel microbiota-targeted therapies and to better understand the biology underpinning such treatments, we have used gnotobiotic mice to model microbiota manipulations in the context of microbiotas from humans with inflammatory bowel disease. Mice colonized with IBD donor-derived microbiotas exhibit a stereotypical set of phenotypes, characterized by abundant mucosal Th17 cells, a deficit in the tolerogenic RORγt regulatory T (Treg) cell subset, and susceptibility to disease in colitis models. Transplanting healthy donor-derived microbiotas into mice colonized with human IBD microbiotas led to induction of RORγt Treg cells, which was associated with an increase in the density of the microbiotas following transplant. Microbiota transplant reduced gut Th17 cells in mice colonized with a microbiota from a donor with Crohn's disease. By culturing strains from this microbiota and screening them in vivo, we identified a specific strain that potently induces Th17 cells. Microbiota transplants reduced the relative abundance of this strain in the gut microbiota, which was correlated with a reduction in Th17 cells and protection from colitis.
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http://dx.doi.org/10.1073/pnas.1922189117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7474624PMC
September 2020

Simple water-based tacrolimus enemas for refractory proctitis.

JGH Open 2020 Aug 14;4(4):561-564. Epub 2019 Nov 14.

Department of Gastroenterology St Vincent's Hospital Melbourne Victoria Australia.

Background And Aims: Rectal ulcerative colitis (UC) and Crohn's disease (CD) often do not respond to conventional therapies. Oral and suppository tacrolimus are effective but often poorly tolerated or are complex to formulate. Tacrolimus is topically active, water soluble, and has minimal systemic toxicity when administered rectally; we therefore tested a simple tap water-based enema formulation.

Methods: Tacrolimus powder from 1 mg capsules and tap water in a 60 mL syringe were delivered rectally. The primary end-point was endoscopic response (UC: MAYO score reduction by one point; CD: improvement in ulcer number and severity). Secondary end-points included endoscopic remission, clinical response, stool frequency, and rectal bleeding.

Results: Seventeen patients [12 UC, five CD, nine female, median age 31 years] with refractory rectal disease were treated. The majority of patients had failed immunosuppressive therapy [88% thiopurine; 71% biologic therapy]. Initial enemas included 1-4 mg tacrolimus daily and 1-3 mg tacrolimus maintenance three times a week for a median of 20 weeks (range 3-204). Concomitant thiopurine or biologic therapy continued. 94% tolerated therapy. Of 12 UC patients, eight (67%) achieved endoscopic remission, one further patient achieved endoscopic response, and median partial MAYO scores decreased (pre:4 vs. post:2; = 0.010). Of five CD patients, three (60%) achieved endoscopic response, two (40%) endoscopic remission, and three (60%) clinical response. Stool frequency, rectal bleeding, and C-reactive protein levels improved. Strictures became endoscopically passable in all four affected patients. No major adverse events were reported, and four patients had disease flare.

Conclusions: Tacrolimus enemas are easy to prepare, well tolerated, effective, and safe. They should be included in the treatment armamentarium for inflammatory bowel disease-related refractory proctitis.
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http://dx.doi.org/10.1002/jgh3.12280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411644PMC
August 2020

Standard gastroenterologist versus multidisciplinary treatment for functional gastrointestinal disorders (MANTRA): an open-label, single-centre, randomised controlled trial.

Lancet Gastroenterol Hepatol 2020 10 14;5(10):890-899. Epub 2020 Jul 14.

Department of Gastroenterology, University of Melbourne, Melbourne, VIC, Australia; Department of Medicine St Vincent's Hospital, University of Melbourne, Melbourne, VIC, Australia.

Background: Functional gastrointestinal disorders are common and costly to the health-care system. Most specialist care is provided by a gastroenterologist, but only a minority of patients have improvement in symptoms. Although they have proven to be effective, psychological, behavioural, and dietary therapies are not provided routinely. We aimed to compare the outcome of gastroenterologist-only standard care with multidisciplinary care.

Methods: In an open-label, single-centre, pragmatic trial, consecutive new referrals of eligible patients aged 18-80 years with Rome IV criteria-defined functional gastrointestinal disorders were randomly assigned (1:2) to receive gastroenterologist-only standard care or multidisciplinary clinic care. The multidisciplinary clinic included gastroenterologists, dietitians, gut-focused hypnotherapists, psychiatrists, and behavioural (biofeedback) physiotherapists. Randomisation was stratified by Rome IV disorder and whether referred from gastroenterology or colorectal clinic. Outcomes were assessed at clinic discharge or 9 months after the initial visit. The primary outcome was a score of 4 (slightly better) or 5 (much better) on a 5-point Likert scale assessing global symptom improvement. Modified intention-to-treat analysis included all patients who attended at least one clinic visit and who had answered the primary outcome question. This study is registered with ClinicalTrials.gov, NCT03078634.

Findings: Between March 16, 2017, and May 10, 2018, 1632 patients referred to the hospital gastrointestinal clinics were screened, of whom 442 were eligible for a screening telephone call and 188 were randomly assigned to receive either standard care (n=65) or multidisciplinary care (n=123). 144 patients formed the modified intention-to-treat analysis (n=46 in the standard-care group and n=98 in the multidisciplinary-care group), 90 (63%) of whom were women. 61 (62%) of 98 patients in the multidisciplinary-care group patients saw allied clinicians. 26 (57%) patients in the standard-care group and 82 (84%) patients in the multidisciplinary-care group had global symptom improvement (risk ratio 1·50 [95% CI 1·13-1·93]; p=0·00045). 29 (63%) patients in the standard-care group and 81 (83%) patients in the multidisciplinary-care group had adequate relief of symptoms in the past 7 days (p=0·010). Patients in the multidisciplinary-care group were more likely to experience a 50% or higher reduction in all Gastrointestinal Symptom Severity Index symptom clusters than were patients in the standard-care group. Of the patients with irritable bowel syndrome, a 50-point or higher reduction in IBS-SSS occurred in 10 (38%) of 26 patients in the standard care group compared with 39 (66%) of 59 patients in the multidisciplinary-care group (p=0·017). Of the patients with functional dyspepsia, a 50% reduction in the Nepean Dyspepsia Index was noted in three (11%) of 11 patients in the standard-care group and in 13 (46%) of 28 in the multidisciplinary-care group (p=0·47). After treatment, the median HADS scores were higher in the standard-care group than in the multidisciplinary-care group (13 [8-20] vs 10 [6-16]; p=0·096) and the median EQ-5D-5L quality of life visual analogue scale was lower in the standard-care group compared with the multidisciplinary-care group (70 [IQR 50-80] vs 75 [65-85]; p=0·0087). The eight SF-36 scales did not differ between the groups at discharge. After treatment, median Somatic Symptom Scale-8 score was higher in the standard-care group than in the multidisciplinary-care group (10 [IQR 7-7] vs 9 [5-13]; p=0·082). Cost per successful outcome was higher in the standard-care group than the multidisciplinary-care group.

Interpretation: Integrated multidisciplinary clinical care appears to be superior to gastroenterologist-only care in relation to symptoms, specific functional disorders, psychological state, quality of life, and cost of care for the treatment of functional gastrointestinal disorders. Consideration should be given to providing multidisciplinary care for patients with a functional gastrointestinal disorder.

Funding: None.
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http://dx.doi.org/10.1016/S2468-1253(20)30215-6DOI Listing
October 2020

Luminal microbiota related to Crohn's disease recurrence after surgery.

Gut Microbes 2020 11 21;11(6):1713-1728. Epub 2020 Jun 21.

Cambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, Australia and Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge , Cambridge, UK.

Background: Microbial factors are likely to be involved in the recurrence of Crohn's disease (CD) after bowel resection. We investigated the luminal microbiota before and longitudinally after surgery, in relation to disease recurrence, using 16S metagenomic techniques.

Methods: In the prospective Post-Operative Crohn's Endoscopic Recurrence (POCER) study, fecal samples were obtained before surgery and 6, 12, and 18 months after surgery from 130 CD patients. Endoscopy was undertaken to detect disease recurrence, defined as Rutgeerts score ≥i2, at 6 months in two-thirds of patients and all patients at 18 months after surgery. The V2 region of the 16S rRNA gene was sequenced using Illumina MiSeq. Cluster analysis was performed at family level, assessing microbiome community differences between patients with and without recurrence.

Results: Six microbial cluster groups were identified. The cluster associated with maintenance of remission was enriched for the family [adjusted OR 0.47 (0.27-0.82), = .007]. The OTU diversity of within this cluster was significantly greater than in all other clusters. The cluster enriched for was associated with an increased risk of disease recurrence [adjusted OR 6.35 (1.24-32.44), = .026]. OTU diversity of within this cluster was significantly greater than in other clusters.

Conclusions: Luminal bacterial communities are associated with protection from, and the occurrence of, Crohn's disease recurrence after surgery. Recurrence may relate to a higher abundance of facultatively anaerobic pathobionts from the family. The ecologic change of depleted , a genus of butyrate-producing bacteria, may permit expansion of through luminal environmental perturbation.
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http://dx.doi.org/10.1080/19490976.2020.1778262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524166PMC
November 2020

Fungal Trans-kingdom Dynamics Linked to Responsiveness to Fecal Microbiota Transplantation (FMT) Therapy in Ulcerative Colitis.

Cell Host Microbe 2020 05 15;27(5):823-829.e3. Epub 2020 Apr 15.

Gastroenterology and Hepatology Division, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, NY 10065, USA; Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, Cornell University, New York, NY 10065, USA; The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA. Electronic address:

Fecal microbiota transplantation (FMT) targeting gut microbiota has recently been successfully applied to ulcerative colitis. However, only a subset of patients responds to FMT, and there is a pressing need for biomarkers of responsiveness. Fungi (the mycobiota) represent a highly immunologically reactive component of the gut microbiota. We analyzed samples from a large randomized controlled trial of FMT for ulcerative colitis (UC). High Candida abundance pre-FMT was associated with a clinical response, whereas decreased Candida abundance post-FMT was indicative of ameliorated disease severity. High pre-FMT Candida was associated with increased bacterial diversity post-FMT, and the presence of genera was linked to FMT responsiveness. Although we detected elevated anti-Candida antibodies in placebo recipients, this increase was abrogated in FMT recipients. Our data suggest that FMT might reduce Candida to contain pro-inflammatory immunity during intestinal disease and highlight the utility of mycobiota-focused approaches to identify FMT responders prior to therapy initiation.
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http://dx.doi.org/10.1016/j.chom.2020.03.006DOI Listing
May 2020

Development and Validation of Surveys to Estimate Food Additive Intake.

Nutrients 2020 Mar 19;12(3). Epub 2020 Mar 19.

Department of Gastroenterology, St Vincent's Hospital, Melbourne 3065, Australia.

(1) Background: The Food Agricultural Organization/World Health Organization (FAO/WHO) International Food Standards (hereafter, CODEX) declares additives non-toxic, but they have been associated with changes to the microbiota changes and thinning of the mucus layer of the gut. Their widespread use has occurred in parallel with increased inflammatory bowel disease (IBD) incidence. This paper reports on the development and validation of surveys to estimate additive intake. (2) Methods: Dietitians created a food-additive database, with a focus on additives that have been associated with IBD. For each additive, information on the CODEX food-category they are permitted in and the associated maximum permissible levels (mg/kg) was recorded. Based on the database, questions to assess early life (part 1) and recent (part 2) additive intake were written. Forward-backward translation from English to Chinese was undertaken. Thirty-one individuals were evaluated to assess understandability. A further fifty-seven individuals completed the tool on two occasions, a fortnight apart; agreement was assessed using Cohen's kappa coefficient or the intra-class correlation coefficient (ICC). (3) Results: The participants reported that it was difficult to remember food intake and estimate portion sizes. The participants also noted confusion around the term 'home-grown'. Instructions and definitions were added; after this, respondents judged the questionnaires as clear. The average kappa coefficient for part 1 and part 2 questions were 0.61 and 0.67, respectively. The average ICC ranged from 0.30 to 0.94; three food lists were removed due to low reliability. (4) Conclusions: Two tools have been created and validated, in two languages, that reliably assess remote and recent food additive intake.
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http://dx.doi.org/10.3390/nu12030812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7146549PMC
March 2020

Dietary Guidance From the International Organization for the Study of Inflammatory Bowel Diseases.

Clin Gastroenterol Hepatol 2020 05 15;18(6):1381-1392. Epub 2020 Feb 15.

Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address:

Recent evidence points to a plausible role of diet and the microbiome in the pathogenesis of both Crohn's disease (CD) and Ulcerative Colitis (UC). Dietary therapies based on exclusion of table foods and replacement with nutritional formulas and/or a combination of nutritional formulas and specific table foods may induce remission in CD. In UC, specific dietary components have also been associated with flare of disease. While evidence of varying quality has identified potential harmful or beneficial dietary components, physicians and patients at the present time do not have guidance as to which foods are safe, may be protective or deleterious for these diseases. The current document has been compiled by the nutrition cluster of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) based on the best current evidence to provide expert opinion regarding specific dietary components, food groups and food additives that may be prudent to increase or decrease in the diet of patients with inflammatory bowel diseases to control and prevent relapse of inflammatory bowel diseases.
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http://dx.doi.org/10.1016/j.cgh.2020.01.046DOI Listing
May 2020

Processed food affects the gut microbiota: The revolution has started.

Authors:
Michael A Kamm

J Gastroenterol Hepatol 2020 Jan;35(1):6-7

St Vincent's Hospital, Melbourne, Victoria, Australia.

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http://dx.doi.org/10.1111/jgh.14976DOI Listing
January 2020

Systematic review: Pelvic floor muscle training for functional bowel symptoms in inflammatory bowel disease.

JGH Open 2019 Dec 24;3(6):494-507. Epub 2019 Jun 24.

Department of Gastroenterology St Vincent's Hospital Australia.

Background And Aim: Large bowel functional symptoms are common in patients with inflammatory bowel disease (IBD) who are in disease remission. The efficacy of pelvic floor muscle training for symptoms of evacuation difficulty or fecal incontinence is well established in patients without organic bowel disease but is unknown in these patients. This study aimed to systematically evaluate the published evidence in this group of patients.

Methods: A systematic review was conducted of articles evaluating pelvic floor muscle training, with or without biofeedback, to improve bowel function in patients with quiescent IBD, including those with an ileoanal pouch. The outcome of interest was improved bowel function measured by bowel diary, patient report, or validated questionnaire in randomized controlled studies, cohort studies, or case series.

Results: Two randomized controlled trials, four retrospective case series, and one prospective study met eligibility criteria. Pelvic floor muscle training for patients with quiescent IBD improved symptoms in 51 of 76 (68%) patients with evacuation difficulty and 20 of 25 (80%) patients with fecal incontinence. Pelvic floor muscle training for patients with an ileoanal pouch, prior to stoma closure, did not appear to reduce the risk or severity of fecal incontinence following stoma closure. Studies were limited by small numbers, study design, methodological quality, and lack of long-term follow-up.

Conclusion: Pelvic floor muscle training appears to be of therapeutic value in some patients with quiescent IBD and evacuation difficulty or fecal incontinence. The effectiveness of this approach warrants further investigation.
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http://dx.doi.org/10.1002/jgh3.12207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6891014PMC
December 2019

Magnetic resonance enterography for predicting the clinical course of Crohn's disease strictures.

J Gastroenterol Hepatol 2020 Jun 11;35(6):980-987. Epub 2019 Nov 11.

Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia.

Background And Aims: Strictures are the most common Crohn's disease complication, but their natural history is unknown. This study aimed to characterize inflammation, predict prognosis, and understand the impact of drug therapy using magnetic resonance enterography (MRE).

Methods: Patients with a stricture diagnosed on MRE over a 5-year period were reviewed for MRE disease extent and inflammation, clinical course, C-reactive protein, response to anti-TNF therapy, endoscopic dilatation, hospitalization, and surgery.

Results: 136 patients had 235 strictures (77, one and 59, ≥ 2 strictures).

Treatment: 46% of patients underwent surgery after a median 6 months; median follow-up for those not requiring surgery was 41 months. Predictors of surgery: Hospitalization because of obstruction predicted subsequent surgery (OR 2.50; 95% CI 1.06-5.90) while anti-TNF therapy commenced at stricture diagnosis was associated with a reduced risk (OR 0.23; 95% CI 0.05-0.99). MRE characteristics associated with surgery were proximal bowel dilatation ≥ 30-mm diameter (OR 2.98; 95% CI 1.36-6.55), stricture bowel wall thickness ≥ 10-mm (OR 2.42; 95% CI 1.11-5.27), and stricture length > 5-cm (OR 2.56; 95% CI 1.21-5.43). 81% of patients with these three adverse MRE features required surgery versus 17% if none were present (P < 0.001). Accuracy for these three MRE variables predicting surgery was high (AUC 0.76).

Conclusion: Magnetic resonance enterography findings in Crohn's disease strictures are highly predictive of the disease course and the need for future surgery. MRE may also identify who would benefit from treatment intensification. Anti-TNF therapy is associated with reduced risk of surgery and appears to alter the natural history of this complication.
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http://dx.doi.org/10.1111/jgh.14908DOI Listing
June 2020

Scientific frontiers in faecal microbiota transplantation: joint document of Asia-Pacific Association of Gastroenterology (APAGE) and Asia-Pacific Society for Digestive Endoscopy (APSDE).

Gut 2020 01 14;69(1):83-91. Epub 2019 Oct 14.

Center for Gut Microbiota Research, The Chinese University of Hong Kong, Hong Kong, China.

Objective: The underlying microbial basis, predictors of therapeutic outcome and active constituent(s) of faecal microbiota transplantation (FMT) mediating benefit remain unknown. An international panel of experts presented key elements that will shape forthcoming FMT research and practice.

Design: Systematic search was performed, FMT literature was critically appraised and a 1-day round-table discussion was conducted to derive expert consensus on key issues in FMT research.

Results: 16 experts convened and discussed five questions regarding (1) the role of donor and recipient microbial (bacteria, viruses, fungi) parameters in FMT; (2) methods to assess microbiota alterations; (3) concept of keystone species and microbial predictors of FMT, (4) influence of recipient profile and antibiotics pretreatment on FMT engraftment and maintenance and (5) new developments in FMT formulations and delivery. The panel considered that variable outcomes of FMT relate to compositional and functional differences in recipient's microbiota, and likely donor-associated and recipient-associated physiological and genetic factors. Taxonomic composition of donor intestinal microbiota may influence the efficacy of FMT in recurrent infections and UC. FMT not only alters bacteria composition but also establishes trans-kingdom equilibrium between gut fungi, viruses and bacteria to promote the recovery of microbial homeostasis. FMT is not a one size fits all and studies are required to identify microbial components that have specific effects in patients with different diseases.

Conclusion: FMT requires optimisation before their therapeutic promise can be evaluated for different diseases. This summary will guide future directions and priorities in advancement of the science and practice of FMT.
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http://dx.doi.org/10.1136/gutjnl-2019-319407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943253PMC
January 2020

Defining Optimal Care for Functional Gut Disorders - Multi-Disciplinary Versus Standard Care: A Randomized Controlled Trial Protocol.

Contemp Clin Trials 2019 09 19;84:105828. Epub 2019 Aug 19.

Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia; University of Melbourne, Melbourne, Australia. Electronic address:

Background: Functional gastrointestinal disorders (FGIDs) are the commonest reason for gastroenterological consultation, with patients usually seen by a specialist working in isolation. There is a wealth of evidence testifying to the benefit provided by dieticians, behavioral therapists, hypnotherapists and psychotherapists in treating these conditions, yet they rarely form a part of the therapeutic team, and these treatment modalities are rarely offered as part of the therapeutic management. There has been little examination of different models of care for FGIDs. We hypothesize that multi-disciplinary integrated care is superior to standard specialist-based care in the treatment of functional gut disorders.

Methods: The "MANTRA" (Multidisciplinary Treatment for Functional Gut Disorders) study compares comprehensive multi-disciplinary outpatient care with standard hospital outpatient care. Consecutive new referrals to the gastroenterology and colorectal outpatient clinics of a single secondary and tertiary care hospital of patients with an FGID, defined by the Rome IV criteria, will be included. Patients will be prospectively randomized 2:1 to multi-disciplinary (gastroenterologist, gut-hypnotherapist, psychiatrist, behavioral therapist ('biofeedback') and dietician) or standard care (gastroenterologist or colorectal surgeon). Patients are assessed up to 12 months after completing treatment. The primary outcome is an improvement on a global assessment scale at the end of treatment. Symptoms, quality of life, psychological well-being, and healthcare costs are secondary outcome measures.

Discussion: There have been few studies examining how best to deliver care for functional gut disorders. The MANTRA study will define the clinical and cost benefits of two different models of care for these highly prevalent disorders.

Trial Registration Number: Clinicaltrials.govNCT03078634 Registered on Clinicaltrials.gov, completed recruitment, registered on March 13th 2017. Ethics and Dissemination: Ethical approval has been received by the St Vincent's Hospital Melbourne human research ethics committee (HREC-A 138/16). The results will be disseminated in peer-reviewed journals and presented at international conferences. Protocol version 1.2.
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http://dx.doi.org/10.1016/j.cct.2019.105828DOI Listing
September 2019

Delivery of care for functional gastrointestinal disorders: A systematic review.

J Gastroenterol Hepatol 2020 Feb 3;35(2):204-210. Epub 2019 Sep 3.

Department of Gastroenterology, St. Vincent's Hospital, Melbourne, Victoria, Australia.

Background: A diverse range of treatments are available for the treatment of functional gastrointestinal disorders (FGIDs). Individual treatments, including drug therapies, behavioral therapy ("biofeedback"), psychological therapies, and dietary therapies, have been well validated in controlled, randomized trials and real-life case series. However, few studies have evaluated models of delivery of care for the whole population of referred patients with an FGID. This review evaluates models of specialist outpatient care for the management of FGIDs.

Methods: A systematic review was performed of full-text articles published until October 2018 in Pubmed/Medline and Embase. Studies were included if they evaluated a model of outpatient care in a specialist setting for the treatment of adult patients with an FGID and included patient-reported outcomes comprising symptoms, quality of life, or psychological well-being.

Results: Few studies have evaluated the delivery of care for the whole population of referred patients with an FGID, and there was one randomized comparison of different models of care. Two studies that evaluated the outcome of gastroenterologist-only clinics suggested poor long-term results. Two non-comparative case series reported the outcome of multidisciplinary care, including gastroenterologists and psychological therapists, suggesting improved patient quality of life and psychological well-being.

Conclusions: Despite the high prevalence and cost of treating FGIDs, and the availability of effective treatments, there are few data and limited randomized comparisons reporting the outcome of different types of specialist care. The few data available suggest that multidisciplinary care is superior to gastroenterologist-only care, but this needs to be validated in prospective comparative studies.
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http://dx.doi.org/10.1111/jgh.14830DOI Listing
February 2020

Anti-TNF Therapy in Pregnant Women With Inflammatory Bowel Disease: Effects of Therapeutic Strategies on Disease Behavior and Birth Outcomes.

Inflamm Bowel Dis 2020 01;26(1):93-102

Department of Gastroenterology, St Vincent's Hospital, and University of Melbourne, Melbourne, Australia.

Background: Active inflammatory bowel disease (IBD) adversely affects pregnancy outcomes. Little is known about the risk of relapse after stopping anti-tumor necrosis factor (anti-TNF) treatment during pregnancy. We assessed the risk of relapse before delivery in women who discontinued anti-TNF treatment before gestational week (GW) 30, predictors of reduced infant birth weight, a marker associated with long-term adverse outcomes, and rates and satisfaction with counseling.

Methods: Pregnant women with IBD receiving anti-TNF treatment were prospectively invited to participate in an electronic questionnaire carried out in 22 hospitals in Denmark, Australia, and New Zealand from 2011 to 2015. Risk estimates were calculated, and birth weight was investigated using t tests and linear regression.

Results: Of 175 women invited, 153 (87%) responded. In women in remission, the relapse rate did not differ significantly between those who discontinued anti-TNF before GW 30 (1/46, 2%) compared with those who continued treatment (8/74, 11%; relative risk, 0.20; 95% confidence interval [CI], 0.02 to 1.56; P = 0.08). Relapse (P = 0.001) and continuation of anti-TNF therapy after GW 30 (P = 0.007) were independently associated with reduced mean birth weight by 367 g (95% CI, 145 to 589 g; relapse) and 274 g (95% CI, 77 to 471 g; anti-TNF exposure after GW 30). Of 134 (88%) women who received counseling, 116 (87%) were satisfied with the information provided.

Conclusions: To minimize fetal exposure in women in remission, discontinuation of anti-TNF before GW 30 seems safe. Relapse and continuation of anti-TNF therapy after GW 30 were each independently associated with lower birth weight, although without an increased risk for birth weight <2500 g. Most women received and were satisfied with counseling.
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http://dx.doi.org/10.1093/ibd/izz110DOI Listing
January 2020

Systematic review with meta-analysis: review of donor features, procedures and outcomes in 168 clinical studies of faecal microbiota transplantation.

Aliment Pharmacol Ther 2019 02 9;49(4):354-363. Epub 2019 Jan 9.

Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Disease, LKS Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.

Background: Faecal microbiota transplantation (FMT) is effective for Clostridium difficile infections (CDI) refractory to standard treatment and is being studied in other diseases.

Aim: To evaluate donor characteristics, procedures and clinical outcomes of FMT.

Methods: We systematically reviewed FMT studies published up to 29 August 2018 using MEDLINE (R) and EMBASE and identified clinical studies with FMT donor information. We reported data on donor characteristics, screening criteria, administration, clinical outcomes and adverse events.

Results: Among 5267 reports, 239 full-text articles were screened and 168 articles were included. FMT was performed commonly for CDI (n = 108) and inflammatory bowel disease (IBD) (n = 31). We reported characteristics of 1513 donors [58% male; mean age, 34.3 years; mean body mass index, 21.6]. Donors in Asia were younger than the West (mean age 30.7 vs 32.9, P = 0.00075). Less than 50% of studies screened donors for transmittable pathogens. Final cure rate for CDI was 95.6% (95% confidence interval [CI], 93.9%-97.1%) and final remission rates for ulcerative colitis (UC) and Crohn's disease (CD) were 39.6% (95% CI, 25.4%-54.6%) and 47.5% (95% CI, 29.4%-65.8%), respectively. Cure rates in CDI and final remission rates for CD and UC were comparable across all routes of FMT administration. Overall adverse event incidence was <1%, mostly GI-related. Adverse event rates did not differ significantly between routes of FMT administration or indication.

Conclusions: In a systematic review assessing donor characteristics and FMT efficacy, we observed heterogeneity in donor selection, application and outcomes of FMT. These data can facilitate standardisation of FMT protocols for various diseases.
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http://dx.doi.org/10.1111/apt.15116DOI Listing
February 2019

Specific Bacteria and Metabolites Associated With Response to Fecal Microbiota Transplantation in Patients With Ulcerative Colitis.

Gastroenterology 2019 Apr 6;156(5):1440-1454.e2. Epub 2018 Dec 6.

University of New South Wales, Sydney, Australia. Electronic address:

Background & Aims: Fecal microbiota transplantation (FMT) can induce remission in patients with ulcerative colitis (UC). In a randomized controlled trial of FMT in patients with active UC, we aimed to identify bacterial taxonomic and functional factors associated with response to therapy.

Methods: We performed a double-blind trial of 81 patients with active UC randomly assigned to groups that received an initial colonoscopic infusion and then intensive multidonor FMT or placebo enemas, 5 d/wk for 8 weeks. Patients in the FMT group received blended homogenized stool from 3-7 unrelated donors. Patients in the placebo group were eligible to receive open-label FMT after the double-blind study period. We collected 314 fecal samples from the patients at screening, every 4 weeks during treatment, and 8 weeks after the blinded or open-label FMT therapy. We also collected 160 large-bowel biopsy samples from the patients at study entry, at completion of 8 weeks of blinded therapy, and at the end of open-label FMT, if applicable. We analyzed 105 fecal samples from the 14 individual donors (n = 55), who in turn contributed to 21 multidonor batches (n = 50). Bacteria in colonic and fecal samples were analyzed by both 16S ribosomal RNA gene and transcript amplicon sequencing; 285 fecal samples were analyzed by shotgun metagenomics, and 60 fecal samples were analyzed for metabolome features.

Results: FMT increased microbial diversity and altered composition, based on analyses of colon and fecal samples collected before vs after FMT. Diversity was greater in fecal and colon samples collected before and after FMT treatment from patients who achieved remission compared with patients who did not. Patients in remission after FMT had enrichment of Eubacterium hallii and Roseburia inulivorans compared with patients who did not achieve remission after FMT and had increased levels of short-chain fatty acid biosynthesis and secondary bile acids. Patients who did not achieve remission had enrichment of Fusobacterium gonidiaformans, Sutterella wadsworthensis, and Escherichia species and increased levels of heme and lipopolysaccharide biosynthesis. Bacteroides in donor stool were associated with remission in patients receiving FMT, and Streptococcus species in donor stool was associated with no response to FMT.

Conclusions: In an analysis of fecal and colonic mucosa samples from patients receiving FMT for active UC and stool samples from donors, we associated specific bacteria and metabolic pathways with induction of remission. These findings may be of value in the design of microbe-based therapies for UC. ClinicalTrials.gov, Number NCT01896635.
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http://dx.doi.org/10.1053/j.gastro.2018.12.001DOI Listing
April 2019

Editorial: treating strictures in inflammatory bowel disease.

Authors:
Michael A Kamm

Aliment Pharmacol Ther 2018 12;48(11-12):1312-1313

St Vincent's Hospital and University of Melbourne, Melbourne, Vic., Australia.

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http://dx.doi.org/10.1111/apt.14987DOI Listing
December 2018

Gut-Directed Pelvic Floor Behavioral Treatment for Fecal Incontinence and Constipation in Patients with Inflammatory Bowel Disease.

Inflamm Bowel Dis 2019 02;25(3):620-626

Department of Gastroenterology, St Vincent's Hospital, Melbourne and University of Melbourne, Melbourne, Australia.

Background: Patients with inflammatory bowel disease (IBD) often experience functional bowel symptoms despite achieving disease remission. Although behavioral treatment (bowel and pelvic floor muscle retraining) is effective for managing constipation or fecal incontinence in non-IBD patients, there is limited evidence for its efficacy in patients with quiescent inflammatory bowel disease. The aim of this study was to evaluate the outcome of gut-directed behavioral treatment, including pelvic floor muscle training, for symptoms of constipation or fecal incontinence in patients with IBD in disease remission.

Methods: The outcome of consecutive patients with IBD in remission and symptoms of constipation or fecal incontinence was evaluated. Patients referred to a multidisciplinary gastroenterology clinic underwent gut-directed behavioral treatment, including pelvic floor muscle training. The primary outcome was patient-reported rating of change in symptoms on a 7-point Likert scale at the completion of treatment.

Results: Forty IBD patients (median age, 35 years; 80% female; 24 Crohn's disease [CD], 12 ulcerative colitis [UC], 4 UC with ileoanal pouch) with ongoing symptoms of constipation (55%) or fecal incontinence (45%), despite drug therapy, were included. The median symptom duration at referral was 2 years. Thirty-five (87%) completed treatment with a median of 2 sessions. Improvement of "6 = much better" or "7 = very much better" was reported by 77% (17/22) with fecal incontinence and 83% (15/18) with constipation. Improvement occurred irrespective of IBD diagnosis, previous perianal fistulae, colorectal surgery, presence of an ileoanal pouch, or past obstetric trauma.

Conclusions: Behavioral treatment effectively improves functional gut symptoms in a large majority of patients who are in IBD disease remission and who have not responded to drug therapy. 10.1093/ibd/izy344_video1 izy344.video1 5968879349001.
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http://dx.doi.org/10.1093/ibd/izy344DOI Listing
February 2019
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