ORCID Profile
0000-0002-2690-4361
Current Organisation
University of Oxford
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Publisher: Wiley
Date: 12-02-2014
DOI: 10.1111/CODI.12500
Abstract: Persistent perineal sinus (PPS) following proctectomy for inflammatory bowel disease affects about 50% of patients. Up to 33% of cases of PPS remain unhealed at 12 months and the most refractory cases are unhealed at 24 months despite optimal conventional therapy. Reports of hyperbaric oxygen therapy (HBOT) for chronic wounds and Crohn's perianal disease led us to explore perioperative HBOT with rectus abdominis myocutaneous (RAM) flap repair in a highly selected group of patients with extreme PPS who had failed all other interventions. Patients with extreme PPS received preoperative HBOT (a 90-min session at 2.2-2.4 atmospheres, five times per week for 5-6 weeks, for a total of up to 30 sessions), before abdominoperineal PPS excision and perineal reconstruction with vertical or transverse RAM flap repair within 2-4 weeks of completing HBOT. Postoperative HBOT (10 further 90-min sessions) was administered within 2 weeks where practicable. Between 2007 and 2011, four patients with extreme PPS underwent RAM flap repair with preoperative HBOT two also received postoperative HBOT. The median (range) duration of PPS before HBOT was 88.5 (23-156) months. All patients had previously failed multiple (5 to > 35) surgical procedures. Complete healing occurred in all patients at a median (range) follow-up of 2.5 (2-3) months. There were no further hospital admissions for PPS at a median (range) follow-up of 35 (8-64) months. Hyperbaric oxygen therapy combined with PPS excision and perineal reconstruction with a RAM flap led to complete perineal healing in four patients with extreme PPS and appears a safe and effective extension to the therapeutic pathway for exceptionally treatment-refractory PPS.
Publisher: Oxford University Press (OUP)
Date: 31-10-2018
DOI: 10.1093/IBD/IZY338
Publisher: Informa UK Limited
Date: 21-12-2022
DOI: 10.1080/00365521.2021.2015801
Abstract: To understand current thinking and clinical decision-making in the treatment and management of patients with mild-to-moderate ulcerative colitis (UC). This multinational, survey-based study was conducted in 2021. Two meetings were held, involving 11 IBD specialists, that used a series of questions and discussion to identify all factors possibly related to the management of UC. The importance of identified factors was assessed using an online questionnaire covering three scenarios - active disease, remission and patient empowerment. Each factor was scored on a scale of 0 (very-unimportant) to 100 (very-important) within each scenario, by a separate group of healthcare professionals working in IBD. A total of 157 in idual factors were identified by the 11 IBD specialists and scored in the three scenarios by 56 respondents (52 93% specialist gastroenterologists) from Europe and North America (25 45%), South America (19 34%) and the Middle East, Asia and Australia (12 21%). For all scenarios, factors related to educating patients regarding UC and its treatment and understanding of patient goals ranked highest, ahead of clinical considerations regarding disease activity and treatment history. Setting realistic short-term treatment targets was a key consideration. 5-ASA optimisation and use of faecal calprotectin monitoring were core strategies across the three scenarios tested. Support for patients during longer-term management of their disease, starting from initial flare, was an important recurring theme. The current management approach for mild-to-moderate UC was found to be guided primarily by the patient's perspectives and goals, alongside assessment of their medical and disease history.
Publisher: Elsevier BV
Date: 09-2021
DOI: 10.1053/J.GASTRO.2021.05.059
Abstract: Barrett's epithelium measurement using widely accepted Prague C&M classification is highly operator dependent. We propose a novel methodology for measuring this risk score automatically. The method also enables quantification of the area of Barrett's epithelium (BEA) and islands, which was not possible before. Furthermore, it allows 3-dimensional (3D) reconstruction of the esophageal surface, enabling interactive 3D visualization. We aimed to assess the accuracy of the proposed artificial intelligence system on both phantom and endoscopic patient data. Using advanced deep learning, a depth estimator network is used to predict endoscope camera distance from the gastric folds. By segmenting BEA and gastroesophageal junction and projecting them to the estimated mm distances, we measure C&M scores including the BEA. The derived endoscopy artificial intelligence system was tested on a purpose-built 3D printed esophagus phantom with varying BEAs and on 194 high-definition videos from 131 patients with C&M values scored by expert endoscopists. Endoscopic phantom video data demonstrated a 97.2% accuracy with a marginal ± 0.9 mm average deviation for C&M and island measurements, while for BEA we achieved 98.4% accuracy with only ±0.4 cm The proposed methodology automatically extracts Prague C&M scores with high accuracy. Quantification and 3D reconstruction of the entire Barrett's area provides new opportunities for risk stratification and assessment of therapy response.
Publisher: MDPI AG
Date: 09-2018
DOI: 10.3390/NU10091192
Abstract: Background: Rising rates of obesity have been reported in patients with inflammatory bowel disease (IBD) however, prospective data is lacking. The aim of this study is to prospectively evaluate body composition in adults with IBD over 24 months. Methods: Whole body dual energy X-ray absorptiometry (DXA) data was performed at 0 months, 12 months, and 24 months. Bone mineral density (BMD), fat mass index (FMI (kg)/height (m2)), appendicular skeletal muscle index (ASMI (kg)/height (m2)), visceral adipose tissue and the visceral adipose height index (VHI, VAT area (cm3)/height (m2)), and clinical and anthropometric assessments were performed at each time point. Multivariable linear mixed effects regression analyses were performed. Results: Initially, 154 participants were assessed at baseline (70% Crohn’s disease, 55% male, median age 31 years), of whom 129 underwent repeated DXA at 12 months, and 110 underwent repeated DXA at 24 months. Amongst those undergoing repeated DXA, their body mass index (BMI) significantly increased over time, such that by 24 months, 62% of patients were overweight or obese (annual change BMI β = 0.43, 95%CI = [0.18, 0.67], p = 0.0006). Gains in BMI related to increases in both FMI and VHI (β = 0.33, 95%CI = [0.14, 0.53], p = 0.0007 β = 0.08, 95%CI = [0.02, 0.13], p = 0.001 respectively), whereas ASMI decreased (β = −0.07, 95%CI = [−0.12, −0.01], p = 0.01) with a concordant rise in rates of myopenia (OR = 3.1 95%CI = [1.2, 7.7] p = 0.01). Rates of osteopenia and osteoporosis were high (37%), but remained unchanged over time (p = 0.23). Conclusion: Increasing rates of obesity in patients with IBD coincide with decreases in lean muscle mass over time, while high rates of osteopenia remain stable. These previously undocumented issues warrant attention in routine care to prevent avoidable morbidity.
Publisher: Springer Science and Business Media LLC
Date: 22-03-2021
DOI: 10.1186/S12876-021-01621-Y
Abstract: The SCCAI was designed to facilitate assessment of disease activity in ulcerative colitis (UC). We aimed to interrogate the metric properties of in idual items of the SCCAI using item response theory (IRT) analysis, to simplify and improve its performance. The original 9-item SCCAI was collected through TrueColours, a real-time software platform which allows remote entry and monitoring of patients with UC. Data were securely uploaded onto Dementias Platform UK Data Portal, where they were analysed in Stata 16.1 SE. A 2-parameter (2-PL) logistic IRT model was estimated to evaluate each item of the SCCAI for its informativeness (discrimination). A revised scale was generated and re-assessed following systematic removal of items. SCCAI data for 516 UC patients (41 years, SD = 15) treated in Oxford were examined. After initial item deletion (Erythema nodosum, Pyoderma gangrenosum), a 7-item scale was estimated. Discrimination values (information) ranged from 0.41 to 2.52 indicating selected item inefficiency with three items 1.70 which is a suggested discriminatory value for optimal efficiency. Systematic item deletions found that a 4-item scale (bowel frequency day bowel frequency nocturnal urgency to defaecation rectal bleeding) was more informative and discriminatory of trait severity (discrimination values of 1.50 to 2.78). The 4-item scale possesses higher scalability and unidimensionality, suggesting that the responses to items are either direct endorsement (patient selection by symptom ) or non-endorsement of the trait (disease activity). Reduction of the SCCAI from the original 9-item scale to a 4-item scale provides optimum trait information that will minimise response burden. This new 4-item scale needs validation against other measures of disease activity such as faecal calprotectin, endoscopy and histopathology.
Publisher: Oxford University Press (OUP)
Date: 08-09-2018
Abstract: During surveillance colonoscopy of patients with long-standing ulcerative colitis [UC], a variety of dysplastic and non-dysplastic lesions are detected. The aim of this study was to address the diagnostic accuracy of endoscopic characterization of endoscopic trimodal imaging [ETMI] and chromoendoscopy [CE]. ETMI includes the combination of autofluorescence imaging [AFI], narrow band imaging [NBI] and white light endoscopy [WLE]. This is a pre-specified additional analysis of a multi-centre, randomized controlled trial that compared AFI with CE for dysplasia detection in 210 patients with long-standing UC [FIND-UC trial]. In the AFI arm, endoscopists used the ETMI system to record AFI colour, Kudo pit pattern using NBI and WLE for lesion characterization. For AFI, purple colour and ambiguous colour combined with pit pattern type III-V on NBI was considered dysplastic. Kudo pit pattern was described in the CE arm. For pit pattern description using NBI and CE, type III-V was considered dysplastic. Histology was the reference standard. In total, 52 dysplastic and 255 non-dysplastic lesions were detected. Overall sensitivity for real-time prediction of dysplasia was 76.9% (95% confidence interval [CI] 46.2-95.0) for ETMI, and 81.6% [95% CI 65.7-92.3] for CE. Overall negative predictive value [NPV] for ETMI was 96.9% [95% CI 92.0-98.8] and 94.7% [90.2-97.2] for CE. Sensitivity for endoscopic differentiation of dysplastic lesions detected during surveillance of patients with long-standing UC seems limited using ETMI and CE. Future research is warranted as the high NPV indicates that these techniques are valuable for the exclusion of dysplastic lesions [NTR4062].
Publisher: Oxford University Press (OUP)
Date: 12-09-2018
DOI: 10.1093/IBD/IZY278
Abstract: Visceral adipose tissue (VAT) has been proposed to play a pathogenic role in Crohn's disease (CD) however, prospective clinical data are lacking. The aim was to evaluate whether VAT, beyond body mass index (BMI), is associated with CD behavior, disease activity, quality of life (QoL), or outcomes. Body composition data and clinical, anthropometric, disease activity (fecal calprotectin [FC]), and QoL scores were gathered prospectively on adults with CD at 0, 12, and 24 months. BMI and, VAT metrics (visceral adipose tissue volume [cm3]/height [m2] index and VAT:subcutaneous adipose tissue [SAT] ratio) were calculated. Inflammatory bowel disease-related surgery and hospitalization were recorded over extended follow-up (median, 51 months). Multivariable linear mixed effects and logistic regression analyses were performed. Ninety-seven participants were assessed at baseline (55% male median age, 31 years), 84 at 12 months, and 72 at 24 months. VAT:SAT was positively associated with stricturing disease behavior (log odds ratio [OR], 1.7 95% confidence interval [CI], 0.32 to 3 P = 0.01) and elevated FC in patients with ileocolonic disease (β, 1.3 95% CI, 0.32 to 2.3 P = 0.01). VAT:SAT was associated with lower QoL, particularly in those with ileal disease (β, -12 95% CI, -19 to -4.5 P = 0.05). However, no prospective associations were observed between serial VAT measurements and time to surgery or hospitalization. No correlations were found between BMI and disease behavior, activity, or QoL. VAT:SAT, rather than BMI, is associated with stricturing CD behavior, elevated FC, and reduced QoL in a disease distribution-dependent manner. Further studies are required to substantiate the role of VAT as a useful biomarker in CD.
Publisher: Cambridge University Press (CUP)
Date: 08-06-2021
DOI: 10.1017/S0954422421000160
Abstract: There is mounting evidence that microbiome composition is intimately and dynamically connected with host energy balance and metabolism. The gut microbiome is emerging as a novel target for counteracting the chronically positive energy balance in obesity, a disease of pandemic scale which contributes to % of premature deaths. This scoping review explores the potential for therapeutic modulation of gut microbiota as a means of prevention and/or treatment of obesity and obesity-associated metabolic disorders. The evidence base for interventional approaches which have been shown to affect the composition and function of the intestinal microbiome is summarised, including dietary strategies, oral probiotic treatment, faecal microbiota transplantation and bariatric surgery. Evidence in this field is still largely derived from preclinical rodent models, but interventional studies in obese populations have demonstrated metabolic improvements effected by microbiome-modulating treatments such as faecal microbiota transplantation, as well as drawing attention to the unappreciated role of microbiome modulation in well-established anti-obesity interventions, such as dietary change or bariatric surgery. The complex relationship between microbiome composition and host metabolism will take time to unravel, but microbiome modulation is likely to provide a novel strategy in the limited armamentarium of effective treatments for obesity.
Publisher: Wiley
Date: 22-02-2018
DOI: 10.1111/JGH.13923
Abstract: A "treat-to-target" approach has been proposed for ulcerative colitis (UC), with a target of combined clinical and endoscopic remission. The aim of the study was to evaluate the extent to which proposed targets are achieved in real-world care, along with clinician perceptions and potential challenges. A multicentre, retrospective, cross-sectional review of patients with UC attending outpatient services in South Australia was conducted. Clinical and objective assessment of disease activity (endoscopy, histology, and/or biomarkers) was recorded. A survey evaluated gastroenterologists' perceptions of treat to target in UC. Statistical analysis included logistic regression and Fisher's exact tests. Of 246 patients with UC, 61% were in clinical remission (normal bowel habit and no rectal bleeding), 35% in clinical and endoscopic remission (Mayo endoscopic sub-score ≤ 1), and 16% in concordant clinical, endoscopic, and histological (Truelove and Richards' Index) remission. Rather than disease-related factors (extent/activity), clinician-related factors dominated outcome. Hospital location and the choice of therapy predicted combined clinical and endoscopic remission (OR 3.6, 95% CI 1.6-8.7, P < 0.001 OR 3.3, 95% CI 1.1-12.5, P = 0.04, respectively). Clinicians used C-reactive protein more often than endoscopy as a biomarker for disease activity (75% vs 47%, P < 0.001). In the survey, 45/61 gastroenterologists responded, with significant disparity between clinician estimates of targets achieved in practice and real-world data (P < 0.001 for clinical and endoscopic remission). Most patients with UC do not achieve composite clinical and endoscopic remission in "real-world" practice. Clinician uptake of proposed treat-to-target guidelines is a challenge to their implementation.
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1038/MI.2017.74
Publisher: Oxford University Press (OUP)
Date: 16-03-2020
Abstract: Lymphocyte activation gene [LAG]-3 is an immune checkpoint and its expression identifies recently activated lymphocytes that may contribute to inflammation. We investigated the role of LAG-3 by analysing its expression and function in immune cells from blood and tissue of patients with ulcerative colitis [UC]. The phenotypic properties of LAG-3+ T cells were determined by flow cytometry, qRT-PCR and single-cell RNA-sequencing. LAG-3+ cells were quantified and correlated with disease activity. The functional effects of LAG-3+ cells were tested using a depleting anti-LAG-3 monoclonal antibody [mAb] in a mixed lymphocyte reaction [MLR]. LAG-3+ cells in the blood were negligible. LAG-3+ lymphocytes were markedly increased in inflamed mucosal tissue and both frequencies of LAG-3+ T cells and transcript levels of LAG3 correlated with endoscopic severity. LAG-3 expression was predominantly on effector memory T cells, and single-cell RNA-sequencing revealed LAG3 expression in activated and cytokine-producing T cell subsets. Foxp3+CD25hi Tregs also expressed LAG-3, although most mucosal Tregs were LAG-3−. Mucosal LAG-3+ cells produced mainly interferon γ [IFNγ] and interleukin-17A. LAG-3+ cell numbers decreased in patients who responded to biologics, and remained elevated in non-responders. Treatment with a depleting anti-LAG-3 mAb led to a reduction in proliferation and IFNγ production in an MLR. LAG-3+ cells are increased in the inflamed mucosa, predominantly on effector memory T cells with an activated phenotype and their cell numbers positively correlate with disease activity. Depleting LAG-3 eliminates activated proliferating T cells, and hence LAG-3 could be a therapeutic target in UC.
Publisher: Springer Science and Business Media LLC
Date: 10-03-2022
DOI: 10.1038/S41467-022-28898-1
Abstract: The trajectories of acquired immunity to severe acute respiratory syndrome coronavirus 2 infection are not fully understood. We present a detailed longitudinal cohort study of UK healthcare workers prior to vaccination, presenting April-June 2020 with asymptomatic or symptomatic infection. Here we show a highly variable range of responses, some of which (T cell interferon-gamma ELISpot, N-specific antibody) wane over time, while others (spike-specific antibody, B cell memory ELISpot) are stable. We use integrative analysis and a machine-learning approach (SIMON - Sequential Iterative Modeling OverNight) to explore this heterogeneity. We identify a subgroup of participants with higher antibody responses and interferon-gamma ELISpot T cell responses, and a robust trajectory for longer term immunity associates with higher levels of neutralising antibodies against the infecting (Victoria) strain and also against variants B.1.1.7 (alpha) and B.1.351 (beta). These variable trajectories following early priming may define subsequent protection from severe disease from novel variants.
Publisher: Korean Association for the Study of Intestinal Diseases
Date: 31-01-2023
Publisher: Baishideng Publishing Group Inc.
Date: 14-08-2020
Publisher: Elsevier BV
Date: 09-2016
Publisher: BMJ
Date: 28-09-2022
DOI: 10.1136/GUTJNL-2022-327533
Abstract: We aimed to determine whether changes in acute severe colitis (ASC) management have translated to improved outcomes and to develop a simple model predicting steroid non-response on admission. Outcomes of 131 adult ASC admissions (117 patients) in Oxford, UK between 2015 and 2019 were compared with data from 1992 to 1993. All patients received standard treatment with intravenous corticosteroids and endoscopic disease activity scoring (Ulcerative Colitis Endoscopic Index of Severity (UCEIS)). Steroid non-response was defined as receiving medical rescue therapy or surgery. A predictive model developed in the Oxford cohort was validated in Australia and India (Gold Coast University Hospital 2015–2020, n=110 All India Institute of Medical Sciences, New Delhi 2018–2020, n=62). In the 2015–2019 Oxford cohort, 15% required colectomy during admission vs 29% in 1992–1993 (p=0.033), while 71 (54%) patients received medical rescue therapy (27% ciclosporin, 27% anti-tumour necrosis factor, compared with 27% ciclosporin in 1992–1993 (p=0.0015). Admission C reactive protein (CRP) (false discovery rate, p=0.00066), albumin (0.0066) and UCEIS scores (0.015) predicted steroid non-response. A four-point model was developed involving CRP of ≥100 mg/L (one point), albumin of ≤25 g/L (one point), and UCEIS score of ≥4 (1 point) or ≥7 (2 points). Patients scoring 0, 1, 2, 3 and 4 in the validation cohorts had steroid response rates of 100, 75.0%, 54.9%, 18.2% and 0%, respectively. Scoring of ≥3 was 84% (95% CI 0.70 to 0.98) predictive of steroid failure (OR 11.9, 95% CI 10.8 to 13.0). Colectomy rates in the validation cohorts were were 8%–11%. Emergency colectomy rates for ASC have halved in 25 years to 8%–15% worldwide. Patients who will not respond to corticosteroids are readily identified on admission and may be prioritised for early intensification of therapy.
Publisher: Oxford University Press (OUP)
Date: 24-05-2019
Publisher: Rockefeller University Press
Date: 05-12-2019
DOI: 10.1084/JEM.20180649
Abstract: Loss of IL-10 signaling in macrophages (Mφs) leads to inflammatory bowel disease (IBD). Induced pluripotent stem cells (iPSCs) were generated from an infantile-onset IBD patient lacking a functional IL10RB gene. Mφs differentiated from IL-10RB−/− iPSCs lacked IL-10RB mRNA expression, were unable to phosphorylate STAT3, and failed to reduce LPS induced inflammatory cytokines in the presence of exogenous IL-10. IL-10RB−/− Mφs exhibited a striking defect in their ability to kill Salmonella enterica serovar Typhimurium, which was rescuable after experimentally introducing functional copies of the IL10RB gene. Genes involved in synthesis and receptor pathways for eicosanoid prostaglandin E2 (PGE2) were more highly induced in IL-10RB−/− Mφs, and these Mφs produced higher amounts of PGE2 after LPS stimulation compared with controls. Furthermore, pharmacological inhibition of PGE2 synthesis and PGE2 receptor blockade enhanced bacterial killing in Mφs. These results identify a regulatory interaction between IL-10 and PGE2, dysregulation of which may drive aberrant Mφ activation and impaired host defense contributing to IBD pathogenesis.
Publisher: Springer Science and Business Media LLC
Date: 20-04-2018
Publisher: Informa UK Limited
Date: 14-07-2021
Publisher: Elsevier BV
Date: 05-2018
Publisher: Elsevier BV
Date: 10-2021
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Simon Travis.