Imperial College London

Dr Nick Powell

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Clinical Reader in Gastroenterology
 
 
 
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Contact

 

nicholas.powell

 
 
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Location

 

Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

98 results found

Alexander J, Powell N, 2021, A response to HM Garcia Garrido et al., The Lancet Gastroenterology and Hepatology, ISSN: 2468-1253

Journal article

Alexander J, Powell N, 2021, SARS-CoV-2 vaccination in immunosuppressed patients with inflammatory bowel disease: should our approach change?, The Lancet Gastroenterology and Hepatology, ISSN: 2468-1253

Journal article

Talley NJ, Powell N, Walker MM, Jones MP, Ronkainen J, Forsberg A, Kjellstrom L, Hellstrom PM, Aro P, Wallner B, Agreus L, Andreasson Aet al., 2021, Role of smoking in functional dyspepsia and irritable bowel syndrome: three random population-based studies, ALIMENTARY PHARMACOLOGY & THERAPEUTICS, ISSN: 0269-2813

Journal article

Alexander J, Powell N, Teare J, Ibraheim Het al., 2021, Clinical outcomes of patients with corticosteroid refractory immune checkpoint inhibitor induced enterocolitis treated with infliximab, Journal for ImmunoTherapy of Cancer, ISSN: 2051-1426

Journal article

Sebastian S, Walker GJ, Kennedy NA, Conley TE, Patel K, Subramanian S, Kent AJ, Segal JP, Brookes MJ, Bhala N, Gonzalez HA, Hicks LC, Mehta SJ, Lamb CAet al., 2021, Assessment, endoscopy, and treatment in patients with acute severe ulcerative colitis during the COVID-19 pandemic (PROTECT-ASUC): a multicentre, observational, case-control study, LANCET GASTROENTEROLOGY & HEPATOLOGY, Vol: 6, Pages: 271-281

Journal article

Kennedy NA, Goodhand JR, Bewshea C, Nice R, Chee D, Lin S, Chanchlani N, Butterworth J, Cooney R, Croft NM, Hart AL, Irving PM, Kok KB, Lamb CA, Limdi JK, Macdonald J, McGovern DP, Mehta SJ, Murray CD, Patel KV, Pollok RC, Raine T, Russell RK, Selinger CP, Smith PJ, Bowden J, McDonald TJ, Lees CW, Sebastian S, Powell N, Ahmad T, Contributors to the CLARITY IBD studyet al., 2021, Anti-SARS-CoV-2 antibody responses are attenuated in patients with IBD treated with infliximab, Gut, Vol: 70, Pages: 865-875, ISSN: 0017-5749

OBJECTIVE: Antitumour necrosis factor (anti-TNF) drugs impair protective immunity following pneumococcal, influenza and viral hepatitis vaccination and increase the risk of serious respiratory infections. We sought to determine whether infliximab-treated patients with IBD have attenuated serological responses to SARS-CoV-2 infections. DESIGN: Antibody responses in participants treated with infliximab were compared with a reference cohort treated with vedolizumab, a gut-selective anti-integrin α4β7 monoclonal antibody that is not associated with impaired vaccine responses or increased susceptibility to systemic infections. 6935 patients were recruited from 92 UK hospitals between 22 September and 23 December 2020. RESULTS: Rates of symptomatic and proven SARS-CoV-2 infection were similar between groups. Seroprevalence was lower in infliximab-treated than vedolizumab-treated patients (3.4% (161/4685) vs 6.0% (134/2250), p<0.0001). Multivariable logistic regression analyses confirmed that infliximab (vs vedolizumab; OR 0.66 (95% CI 0.51 to 0.87), p=0.0027) and immunomodulator use (OR 0.70 (95% CI 0.53 to 0.92), p=0.012) were independently associated with lower seropositivity. In patients with confirmed SARS-CoV-2 infection, seroconversion was observed in fewer infliximab-treated than vedolizumab-treated patients (48% (39/81) vs 83% (30/36), p=0.00044) and the magnitude of anti-SARS-CoV-2 reactivity was lower (median 0.8 cut-off index (0.2-5.6) vs 37.0 (15.2-76.1), p<0.0001). CONCLUSIONS: Infliximab is associated with attenuated serological responses to SARS-CoV-2 that were further blunted by immunomodulators used as concomitant therapy. Impaired serological responses to SARS-CoV-2 infection might have important implications for global public health policy and individual anti-TNF-treated patients. Serological testing and virus surveillance should be considered to detect suboptimal vaccine responses, persistent infection and viral evolution to inform pub

Journal article

Alexander JL, Moran GW, Gaya DR, Raine T, Hart A, Kennedy NA, Lindsay JO, MacDonald J, Segal JP, Sebastian S, Selinger CP, Parkes M, Smith PJ, Dhar A, Subramanian S, Arasaradnam R, Lamb CA, Ahmad T, Lees CW, Dobson L, Wakeman R, Iqbal TH, Arnott I, Powell Net al., 2021, SARS-CoV-2 vaccination for patients with inflammatory bowel disease: a British Society of Gastroenterology Inflammatory Bowel Disease section and IBD Clinical Research Group position statement, LANCET GASTROENTEROLOGY & HEPATOLOGY, Vol: 6, Pages: 218-224

Journal article

Schroeder J-H, Meissl K, Hromadova D, Lo JW, Neves JF, Howard JK, Helmby H, Powell N, Strobl B, Lord GMet al., 2021, T-Bet controls cellularity of intestinal group 3 innate lymphoid cells, Frontiers in Immunology, Vol: 11, Pages: 1-11, ISSN: 1664-3224

Innate lymphoid cells (ILC) play a significant immunological role at mucosal surfaces such as the intestine. T-bet-expressing group 1 innate lymphoid cells (ILC1) are believed to play a substantial role in inflammatory bowel disease (IBD). However, a role of T-bet-negative ILC3 in driving colitis has also been suggested in mouse models questioning T-bet as a critical factor for IBD. We report here that T-bet deficient mice had a greater cellularity of NKp46-negative ILC3 correlating with enhanced expression of RORγt and IL-7R, but independent of signaling through STAT1 or STAT4. We observed enhanced neutrophilia in the colonic lamina propria (cLP) of these animals, however, we did not detect a greater risk of T-bet-deficient mice to develop spontaneous colitis. Furthermore, by utilizing an in vivo fate-mapping approach, we identified a population of T-bet-positive precursors in NKp46-negative ILC3s. These data suggest that T-bet controls ILC3 cellularity, but does do not drive a pathogenic role of ILC3 in mice with a conventional specific pathogen-free microbiota.

Journal article

Alexander J, Hart A, Segal JP, Powell Net al., 2021, British Society of Gastroenterology Inflammatory Bowel Disease section and IBD Clinical Research Group position statement on SARS-CoV2 Vaccination, The Lancet Gastroenterology and Hepatology, ISSN: 2468-1253

SARS-CoV2 has caused a global health crisis and mass vaccination programmes provide the best opportunity for controlling transmission and protecting populations. Despite the impressive clinical trial results of the BNT162b2 (Pfizer/BioNTech), ChAdOx1 nCoV-19 vaccine (Oxford/AstraZeneca) and mRNA-1273 (Moderna) vaccines, important unanswered questions remain, especially in patients with pre-existing conditions. In this position statement endorsed by the British Society of Gastroenterology Inflammatory Bowel Disease (IBD) section and IBD Clinical Research Group, we consider SARS-CoV2 vaccination strategy in patients with IBD. The risks of SARS-CoV2 vaccination are anticipated to be very low, and we strongly support SARS-CoV2 vaccination in IBD patients. Based on data from previous studies with other vaccines, there are conceptual concerns that protective immune responses to SARS-CoV2 vaccination may be diminished in some IBD patients, such as those taking anti-TNF drugs. However, the benefits of vaccination, even in anti-TNF treated patients, are likely to outweigh these theoretical concerns. Key areas for further research are discussed, including vaccine hesitancy and its effect in the IBD community, the impact of immunosuppression on vaccine efficacy and the search for predictive biomarkers of vaccine success.

Journal article

Alexander J, Powell N, 2020, Ileocolonic histopathological and microbial alterations in the irritable bowel syndrome: A nested community case-control study, Clinical and Translational Gastroenterology, Vol: 12, Pages: e00296-e00296, ISSN: 2155-384X

IntroductionHistopathological alterations in the ileum and colon in irritable bowel syndrome (IBS) are controversial, and normal values are poorly established. We hypothesized that changes in mucosal immune cells characterize IBS and key changes in immune composition are associated with the mucosa-associated microbiota (MaM).MethodsA nested case-control study (48 IBS and 106 controls included) from 745 colonoscopy participants in a random population sample. Intraepithelial lymphocytes (IELs)/100 enterocytes and eosinophils/5 nonoverlapping high-power fields counted; mast cells identified by immunocytochemistry (CD117)/5 high-power fields. Paneth cells quantified per 5 crypts. 16S rRNA gene amplicon sequencing performed on available sigmoid MaM, n = 55 and fecal microbiota, n = 20. Microbiota profiles compared between samples with high and low IEL counts.ResultsIBS had increased IELs in the terminal ileum (relative risk ratio = 1.70, 95% confidence interval 1.08-2.76, P = 0.022 adjusted for age, sex, and smoking). Cecal IELs were increased in IBS-diarrhea (relative risk ratio = 2.03, 95% confidence interval 1.13-3.63, P = 0.017). No difference was observed in alpha diversity of MaM or fecal microbiota based on IEL count. There was no difference in beta diversity of the MaM according to IEL count in the terminal ileal (TI) (P = 0.079). High TI IEL counts associated with a significant expansion of the genus Blautia (P = 0.024) and unclassified Clostridiales (P = 0.036) in colon MaM.DiscussionA modest but significant increase in IELs was observed in IBS vs. controls in a population-based setting. Subtle TI and cecal inflammation may play a pathogenic role in IBS but needs confirmation. Modest but discernible differences in the colonic MaM were seen according to TI IEL count but not IBS status.

Journal article

Ibraheim H, Powell N, 2020, Systematic review with meta-analysis: effectiveness of anti-inflammatory therapy in immune checkpoint inhibitor-induced enterocolitis, Alimentary Pharmacology and Therapeutics, Vol: 52, Pages: 1432-1452, ISSN: 0269-2813

Background: Immune checkpoint inhibitors have revolutionised cancer treatment,but at the cost of off-target immune-mediated organ damage. This includes checkpoint inhibitor-induced enterocolitis which frequently requires hospitalisation andmay be life-threatening. Empirical treatment typically includes corticosteroids andinfliximab, although, no large-scale studies have confirmed their effectiveness.Aim: To investigate the effectiveness of anti-inflammatory therapy in checkpointinhibitor-induced enterocolitis.Methods: We performed a systematic review and meta-analysis of studies reportingclinical outcomes of checkpoint inhibitor-induced enterocolitis in adult cancer patients treated with anti-inflammatory agents. We searched Medline, EMBASE, andthe Cochrane library through April and extracted the proportion of patients responding to anti-inflammatory therapy. Variation in effect size was studied using a randomeffects meta-regression analysis, with checkpoint inhibitor agent and tumour type asthe variables.Results: Data were pooled from 1210 treated patients across 39 studies.Corticosteroids were effective in 59% (95% CI 54- 65) of patients, with response significantly more favourable in patients treated with anti-PD-1/L1 monotherapy, compared with anti-CTLA-4 containing regimens (78%, 95% CI 69-85 vs 56 %, 95% CI49-63, P = 0.003), and more favourable in lung cancer patients compared with melanoma patients (88%, 95% CI 62-97 vs 55%, 95% CI 47-63, P = 0.04). Infliximab waseffective in 81% (95% CI 73-87) of patients, and vedolizumab in 85% (95% CI 60-96).Conclusion: Corticosteroids, infliximab and vedolizumab, are effective in the treatment of checkpoint inhibitor‐induced enterocolitis. Checkpoint inhibitor regimen andcancer type were significant moderators in response to corticosteroid therapy.

Journal article

Powell N, Ibraheim H, Raine T, Speight RA, Papa S, Brain O, Green M, Samaan MA, Spain L, Yousaf N, Hunter N, Eldridge L, Pavlidis P, Irving P, Hayee B, Turajlic S, Larkin J, Lindsay JO, Gore Met al., 2020, British Society of Gastroenterology endorsed guidance for the management of immune checkpoint inhibitor-induced enterocolitis, LANCET GASTROENTEROLOGY & HEPATOLOGY, Vol: 5, Pages: 679-697

Journal article

Favara DM, Spain L, Au L, Clark J, Daniels E, Diem S, Chauhan D, Turajlic S, Powell N, Larkin JM, Yousaf Net al., 2020, Five-year review of corticosteroid duration and complications in the management of immune checkpoint inhibitor-related diarrhoea and colitis in advanced melanoma, ESMO OPEN, Vol: 5

Journal article

Powell N, 2020, Adaptation of the British Society of Gastroenterology guidelines on the management of acute severe ulcerative colitis in the context of the COVID-19 pandemic: a RAND appropriateness panel, Gut, Vol: 69, Pages: 1769-1777, ISSN: 0017-5749

ObjectiveManagement of acute severe ulcerative colitis (ASUC) during the novel coronavirus2019 (COVID-19) pandemic presents significant dilemmas. We aimed to provideCOVID-19-specific guidance using current British Society of Gastroenterology (BSG)guidelines as a reference point.DesignWe convened a RAND appropriateness panel comprising 14 gastroenterologists andan IBD nurse consultant supplemented by surgical and COVID-19 experts. Panellistsrated the appropriateness of interventions for ASUC in the context of severe acuterespiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Median scores anddisagreement index (DI) were calculated. Results were discussed at a moderatedmeeting prior to a second survey.ResultsPanellists recommended that patients with ASUC should be isolated throughout theirhospital stay and should have a SARS-CoV-2 swab performed on admission. Patientswith a positive swab should be discussed with COVID-19 specialists.As per BSG guidance, intravenous hydrocortisone was considered appropriate asinitial management; only in patients with COVID-19 pneumonia was their use deemeduncertain. In patients requiring rescue therapy, infliximab with continuing steroidswas recommended. Delaying colectomy because of COVID-19 was deemedinappropriate.Steroid tapering as per BSG guidance, was deemed appropriate for all patients apartfrom those with COVID-19 pneumonia in whom a 4-6-week taper was preferred. Post-ASUC maintenance therapy was dependent on SARS-CoV-2 status but, in general,biologics were more likely to be deemed appropriate than azathioprine or tofacitinib.Panellists deemed prophylactic anticoagulation post-discharge to be appropriate inpatients with a positive SARS-CoV-2 swab.ConclusionWe have suggested COVID-19-specific adaptations to the BSG ASUC guideline using aRAND Panel.

Journal article

Kennedy NA, Jones G-R, Lamb CA, Appleby R, Arnott I, Beattie RM, Bloom S, Brooks AJ, Cooney R, Dart RJ, Edwards C, Fraser A, Gaya DR, Ghosh S, Greveson K, Hansen R, Hart A, Hawthorne AB, Hayee B, Limdi JK, Murray CD, Parkes GC, Parkes M, Patel K, Pollok RC, Powell N, Probert CS, Raine T, Sebastian S, Selinger C, Smith PJ, Stansfield C, Younge L, Lindsay JO, Irving PM, Lees CWet al., 2020, British Society of Gastroenterology guidance for management of inflammatory bowel disease during the COVID-19 pandemic, Gut, Vol: 69, Pages: 984-990, ISSN: 0017-5749

he COVID-19 pandemic is putting unprecedented pressures on healthcare systems globally. Early insights have been made possible by rapid sharing of data from China and Italy. In the UK, we have rapidly mobilised inflammatory bowel disease (IBD) centres in order that preparations can be made to protect our patients and the clinical services they rely on. This is a novel coronavirus; much is unknown as to how it will affect people with IBD. We also lack information about the impact of different immunosuppressive medications. To address this uncertainty, the British Society of Gastroenterology (BSG) COVID-19 IBD Working Group has used the best available data and expert opinion to generate a risk grid that groups patients into highest, moderate and lowest risk categories. This grid allows patients to be instructed to follow the UK government’s advice for shielding, stringent and standard advice regarding social distancing, respectively. Further considerations are given to service provision, medical and surgical therapy, endoscopy, imaging and clinical trials.

Journal article

Taylor KM, Hanscombe KB, Prescott NJ, Iniesta R, Traylor M, Taylor NS, Fong S, Powell N, Irving PM, Anderson SH, Mathew CG, Lewis CM, Sanderson JDet al., 2020, Genetic and Inflammatory Biomarkers Classify Small Intestine Inflammation in Asymptomatic First-degree Relatives of Patients With Crohn's Disease, CLINICAL GASTROENTEROLOGY AND HEPATOLOGY, Vol: 18, Pages: 908-+, ISSN: 1542-3565

Journal article

Urwyler P, Earnshaw I, Bermudez M, Perucha E, Wu W, Ryan S, Mcdonald L, Karagiannis SN, Taams LS, Powell N, Cope A, Papa Set al., 2020, Mechanisms of checkpoint inhibition-induced adverse events, CLINICAL AND EXPERIMENTAL IMMUNOLOGY, Vol: 200, Pages: 141-154, ISSN: 0009-9104

Journal article

Powell N, Pantazi E, Tsamaki A, Pavlidis P, Li K, Yang F, Parker A, Pin C, Cozzetto D, Minns DH, Stolarczyk E, Savelijeva S, Mohamed R, Lavender P, Afzali B, Digby-Bell J, Tsui T, Kaser A, Friedman J, MacDonald TT, Bewick GA, Lord GMet al., 2020, Interleukin 22 orchestrates a pathological endoplasmic reticulum stress response transcriptional programme in colonic epithelial cells, Gut, Vol: 69, Pages: 478-490, ISSN: 0017-5749

Objective - The functional role of interleukin-22 (IL22) in chronic inflammation is controversial and mechanistic insights into how it regulates target tissue are lacking. In this study, we evaluated the functional role of IL22 in chronic colitis and probed mechanisms of IL22- mediated regulation of colonic epithelial cells. Design – To investigate the functional role of IL22 in chronic colitis and how it regulates colonic epithelial cells we employed a 3-dimentional mini-gut epithelial organoid system,in vivo disease models and transcriptomic datasets in human IBD. Results - As well as inducing transcriptional modules implicated in anti-microbial responses, IL22 also coordinated an endoplasmic reticulum (ER) stress response transcriptional program in colonic epithelial cells. In the colon of patients with active colonic Crohn’s disease (CD), there was enrichment of IL22-responsive transcriptional modules and ER stress response modules. Strikingly, in an IL22-dependent model of chronic colitis, targeting IL22 alleviated colonic epithelial ER stress and attenuated colitis. Pharmacological modulation of the ER stress response similarly impacted the severity of colitis. In patients with colonic CD, antibody blockade of IL12p40, which simultaneously blocks IL12 and IL23, the key upstream regulator of IL22 production, alleviated the colonic epithelial ER stress response. Conclusions- Our data challenge perceptions of IL22 as a predominantly beneficial cytokine in IBD and provide novel insights into the molecular mechanisms of IL22-mediated pathogenicity in chronic colitis. Targeting IL22 regulated pathways and alleviating colonic epithelial ER stress may represent promising therapeutic strategies in patients with colitis

Journal article

Powell N, Ibraheim H, Raine T, Speight A, Papa S, Brain O, Green M, Samaan MA, Spain L, Yousaf N, Hunter N, Eldridge L, Pavlidis P, Irving P, Hayee B, Turajlic S, Larkin J, Lindsay JO, Gore Met al., 2020, BSG endorsed guidance of the management of immune checkpoint inhibitor induced enterocolitis, Lancet Gastroenterology and Hepatology, ISSN: 2468-1253

Immune checkpoint inhibitors (ICPis) are a novel class of cancer treatment that have improved outcomes for a subset of cancer patients. They work by antagonizing important inhibitory immune pathways, thereby augmenting immune mediated anti-tumour responses. However, immune activation is not cancer specific and often results in activation of immune cells in non-cancer tissues resulting in off-target immune-mediated injury and organ dysfunction. Diarrhoea and gastrointestinal tract inflammation are common and sometimes serious side effects of ICPi therapy. Prompt recognition of gastrointestinal toxicity and in many cases rapid institution of anti-inflammatory and/or biological therapy is required to reverse these complications. Optimal management of organ specific complications frequently requires engagement with gastroenterologists to deliver improved outcomes for patients developing ICPi-induced enterocolitis. In this British Society of Gastroenterology (BSG) endorsed guidance document we have developed a consensus framework for the investigation and management of ICPi-induced enterocolitis.

Journal article

Digby-Bell JL, Atreya R, Monteleone G, Powell Net al., 2020, Interrogating host immunity to predict treatment response in inflammatory bowel disease, Nature Reviews Gastroenterology and Hepatology, Vol: 17, Pages: 9-20, ISSN: 1759-5045

IBD treatment is undergoing a transformation with an expanding repertoire of drugs targeting different aspects of the immune response. Three novel classes of drugs have emerged in the past decade that target leukocyte trafficking to the gut (vedolizumab), neutralize key cytokines with antibodies (ustekinumab) and inhibit cytokine signalling pathways (tofacitinib). In advanced development are other drugs for IBD, including therapies targeting other cytokines such as IL-23 and IL-6. However, all agents tested so far are hampered by primary and secondary loss of response, so it is desirable to develop personalized strategies to identify which patients should be treated with which drugs. Stratification of patients with IBD by clinical parameters alone lacks sensitivity, and alternative modalities are now needed to deliver precision medicine in IBD. High-resolution profiling of immune response networks in individual patients is a promising approach and different technical platforms, including in vivo real-time molecular endoscopy, tissue transcriptomics and germline genetics, are promising tools to help predict responses to specific therapies. However, important challenges remain regarding the clinical utility of these technologies, including their scalability and accessibility. This Review focuses on unravelling some of the complexity of mucosal immune responses in IBD pathogenesis and how current and emerging analytical platforms might be harnessed to effectively stratify and individualise IBD therapy.

Journal article

Treveil A, Pavlidis P, Tsakmaki A, Bewick G, Korcsmaros T, Powell Net al., 2020, Cytokine responsive transcriptional networks in inflammatory bowel disease, Publisher: OXFORD UNIV PRESS, Pages: S164-S164, ISSN: 1873-9946

Conference paper

Ibraheim H, Samaan MA, Srinivasan A, Brain O, Digby-Bell J, Irving PM, Norman I, Jawad I, Biedermann J, Ibarra A, Kok KB, Parkes G, Rimmer J, Compot E, Parkes M, Segal J, Oppong P, Hart A, Hayee B, Powell Net al., 2020, Effectiveness and safety of vedolizumab in inflammatory bowel disease patients aged 60 and over: an observational multicenter UK experience, Annals of Gastroenterology, Vol: 33, Pages: 1-10, ISSN: 1108-7471

Background The GEMINI trials established the efficacy of vedolizumab in moderate-to-severeinflammatory bowel disease (IBD) and demonstrated a favorable safety profile, suggesting it maybe advantageous in older patients at greater risk of treatment-related complications. However,there is a paucity of data exploring the outcomes of vedolizumab in this group. Our objective wasto determine the clinical effectiveness and safety of vedolizumab in older IBD patients within areal-world multicenter UK cohort.Methods A retrospective review of electronic records across 6 UK hospitals was undertaken toevaluate the clinical effectiveness and safety outcomes of vedolizumab in IBD patients aged ≥60at start of therapy. Rates of clinical response, remission and corticosteroid-free remission wereassessed at weeks 14 and 52, using validated clinical indices, and were compared to historicalcontrols from real-world vedolizumab-treated cohorts unstratified by age.Results Of 74 patients aged 60 years or above (median 66 years), 48 were included in oureffectiveness analysis (29 ulcerative colitis, 19 Crohn’s disease). Rates of clinical response, remissionand corticosteroid-free remission at week 14 were 64%, 48% and 30%, respectively. By week 52, therates of clinical response, remission, and corticosteroid-free remission were 52%, 38%, and 32%,respectively. Six (8%) patients experienced adverse effects. Effectiveness and safety outcomes werecomparable to those of age-unstratified vedolizumab-treated cohorts.Conclusion Our 1-year outcome data suggests that vedolizumab is safe and effective in older IBDpatients and broadly comparable to cohorts unselected by age.

Journal article

Omer OS, Powell N, Lord GM, 2020, Characterizing Innate Lymphoid Cell Phenotype and Function in Human Inflammatory Bowel Disease., Pages: 199-211

Innate lymphoid cells (ILCs) are emerging as important effectors of innate immunity and play a critical role in maintaining intestinal immune homeostasis. They are tissue-residing immune cells that can be subdivided based on master transcription factor and cytokine expression, bearing striking resemblance to their CD4+ T helper (Th) cell counterparts. ILCs are increasingly recognized as potential mediators of inflammatory bowel disease (IBD) providing a need to explore their functional and phenotypic differences in health vs. disease. In this chapter we outline protocols for the characterization of human ILCs and intracellular cytokine expression using flow cytometry. We include protocols for isolating human peripheral blood and colonic lamina propria mononuclear cells essential for evaluating human IBD specimens.

Book chapter

Ibraheim H, Perucha E, Powell N, 2019, Pathology of immune-mediated tissue lesions following treatment with immune checkpoint inhibitors., Rheumatology, Vol: 58, Pages: vii17-vii28, ISSN: 1462-0324

Immune check point inhibitor (CPI) therapy has revolutionized treatment paradigms for several cancers, but at the cost of triggering a diverse spectrum of immune-mediated injury to non-cancer tissues. The complex biology of these toxicities remains incompletely understood, partly because tissue acquisition from affected areas can be challenging to retrieve, thus hindering development of targeted therapy. Here, we review the literature describing pathology of immune-mediated tissue lesions including gastrointestinal, skin, rheumatic, pulmonary, cardiac, renal and hepatic lesions and highlight key immunological insights.

Journal article

Abu-Sbeih H, Faleck D, Ricciuti B, Mendelsohn R, Naqash AR, Cohen J, Sellars M, Balaji A, Ben-betzalel G, Hajir I, Zhang J, Awad M, Leonardi G, Johnson D, Pinato D, Owen D, Weiss S, Lamberti G, Lythgoe M, Manuzzi L, Arnold C, Qiao W, Naidoo J, Markel G, Powell N, Yeung S-C, Sharon E, Dougan M, Wang Yet al., 2019, Immune checkpoint inhibitor therapy in patients with preexisting inflammatory bowel disease, Journal for ImmunoTherapy of Cancer, Vol: 7, Pages: 1-12, ISSN: 2051-1426

PURPOSEThe risk of immune checkpoint inhibitor therapy–related GI adverse events in patients with cancer and inflammatory bowel disease (IBD) has not been well described. We characterized GI adverse events in patients with underlying IBD who received immune checkpoint inhibitors.PATIENTS AND METHODSWe performed a multicenter, retrospective study of patients with documented IBD who received immune checkpoint inhibitor therapy between January 2010 and February 2019. Backward selection and multivariate logistic regression were conducted to assess risk of GI adverse events.RESULTSOf the 102 included patients, 17 received therapy targeting cytotoxic T-lymphocyte antigen-4, and 85 received monotherapy targeting programmed cell death 1 or its ligand. Half of the patients had Crohn’s disease, and half had ulcerative colitis. The median time from last active IBD episode to immunotherapy initiation was 5 years (interquartile range, 3-12 years). Forty-three patients were not receiving treatment of IBD. GI adverse events occurred in 42 patients (41%) after a median of 62 days (interquartile range, 33-123 days), a rate higher than that among similar patients without underlying IBD who were treated at centers participating in the study (11%; P < .001). GI events among patients with IBD included grade 3 or 4 diarrhea in 21 patients (21%). Four patients experienced colonic perforation, 2 of whom required surgery. No GI adverse event–related deaths were recorded. Anti–cytotoxic T-lymphocyte antigen-4 therapy was associated with increased risk of GI adverse events on univariable but not multivariable analysis (odds ratio, 3.19; 95% CI, 1.8 to 9.48; P = .037; and odds ratio, 4.72; 95% CI, 0.95 to 23.53; P = .058, respectively).CONCLUSIONPreexisting IBD increases the risk of severe GI adverse events in patients treated with immune checkpoint inhibitors.

Journal article

Abu-Sbeih H, Faleck D, Ricciuti B, Mendelsohn R, Naqash AR, Cohen J, Sellers M, Balaji A, Ben-Betzalel G, Hajir I, Zhang J, Awad M, Leonardi G, Johnson D, Pinato D, Owen D, Weiss S, Lamberti G, Lythgoe M, Manuzzi L, Arnold C, Naidoo J, Merkel G, Powell N, Yeung S-C, Sharon E, Dougan M, Wang Yet al., 2019, Immune Checkpoint Inhibitor Therapy in Patients With Preexisting Inflammatory Bowel Disease, Annual Scientific Meeting of the American-College-of-Gastroenterology (ACG), Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: S451-S451, ISSN: 0002-9270

Conference paper

Moulton CD, Pavlidis P, Norton C, Norton S, Pariante C, Hayee B, Powell Net al., 2019, Depressive symptoms in inflammatory bowel disease: an extraintestinal manifestation of inflammation?, Clinical and Experimental Immunology, Vol: 197, Pages: 308-318, ISSN: 0009-9104

Depressive symptoms are reported by more than 20% of people with inflammatory bowel disease (IBD), while sleep difficulties and fatigue are even more common. Co-morbid depressive symptoms predict a poor IBD course, including increased risk of relapse and surgery, which is inconsistently improved by psychological treatments. Rather than being distinct systems, there is compelling evidence for bidirectional communication between gut and brain, driven by neural, metabolic, endocrine and inflammatory mediators. An emerging concept is that depressive symptoms may be mechanistically linked to excess inflammation and dysregulation of the gut-brain axis. Given the close link between the intestinal microbiota and host immune responses, patients prone to shifts in their intestinal microbiome, including smokers, those with poor diet and early life stress, may be exposed to exaggerated immune responses. Excess inflammation is associated with brain changes (depressive symptoms, fatigue, sleep difficulties) and worsening gastrointestinal symptoms, which are exacerbated by psychological distress. Equally, treatments both for depressive symptoms and IBD provide opportunities to break this cycle by reducing the causes and effects of inflammation. As well as addressing potential risk factors such as smoking and diet, treatments to alter the microbiome may reduce depressive symptoms. Observational evidence suggests that anti-inflammatory treatments for IBD may improve co-morbid depressive symptoms correlating with reduction in inflammation. With a growing range of treatments targeting inflammation centrally, peripherally and in the gut, IBD provides a unique model to understand the interplay between brain and gut in the pathogenesis of depressive symptoms, both in IBD and in the whole population.

Journal article

Moulton CD, Hopkins CWP, Mohamedali Z, Powell Net al., 2019, Out of sight, out of mind: the limitations of the hospital anxiety and depression scale in inflammatory bowel disease, Inflammatory Bowel Diseases, Vol: 25, Pages: e100-e100, ISSN: 1078-0998

Journal article

Samaan MA, Powell N, Irving PM, 2019, Letter: immune checkpoint inhibitor-induced colitis-shouldn't we be checking more often?, Alimentary Pharmacology and Therapeutics, Vol: 50, Pages: 472-473, ISSN: 0269-2813

Journal article

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