Publications by authors named "Ailsa Hart"

173 Publications

Chronic pain in patients with inflammatory bowel disease.

Pain 2021 10;162(10):2466-2471

Primary Care Centre Versus Arthritis and Centre for Prognosis Research, Keele University, Keele, United Kingdom.

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http://dx.doi.org/10.1097/j.pain.0000000000002304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8442739PMC
October 2021

A multidisciplinary approach to rectal cancer treatment in ulcerative colitis results in high rate of restorative minimally invasive surgery.

J Crohns Colitis 2021 Aug 4. Epub 2021 Aug 4.

IRCCS Humanitas Research Hospital -, via Manzoni, Rozzano, Milan, Italy.

Background And Aims: Few recent studies focus on the treatment of rectal cancer in patients with ulcerative colitis. We report treatment options and results for this subset of patients with a multimodal approach at two European referral centers.

Methods: Ulcerative colitis patients diagnosed with rectal cancer arising at less than 15 cm from the anal verge between January 2010 and December 2020 were analyzed. Demographics, clinical data, details of medical and surgical treatment were retrieved from prospectively collected institutional databases.

Results: Of 132 patients with ulcerative colitis and concomitant colorectal cancer, rectal cancer was diagnosed in 46. The median time between disease onset and rectal cancer diagnosis was 17.5 years. Twenty-one/46 were preoperatively staged as early tumors (cT1-T2/N0). Eleven patients received neoadjuvant chemoradiotherapy for locally advanced extraperitoneal adenocarcinoma, while the rest underwent surgery first. Over two-thirds of the procedures were restorative (68%); a minimally invasive approach was used in 96% of patients with no conversion to open. The median follow-up was 44 months. Local recurrence occurred in 3 patients (6%). The cumulative 3-years cancer-specific survival rate was 94% (and the 3-years disease-free rate was 86%).

Conclusion: Rectal cancer in ulcerative colitis is a very complex condition. Our results show that surgery for rectal cancer can be delivered with excellent oncologic and functional outcomes in patients with ulcerative colitis. A multidisciplinary discussion among surgeons, gastroenterologists, medical oncologists is key to ensure the appropriate treatment pathway for individual patients.
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http://dx.doi.org/10.1093/ecco-jcc/jjab139DOI Listing
August 2021

Supported online self-management versus care as usual for symptoms of fatigue, pain and urgency/incontinence in adults with inflammatory bowel disease (IBD-BOOST): study protocol for a randomised controlled trial.

Trials 2021 Aug 3;22(1):516. Epub 2021 Aug 3.

Psychology Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Background: Despite being in clinical remission, many people with inflammatory bowel disease (IBD) live with fatigue, chronic abdominal pain and bowel urgency or incontinence that limit their quality of life. We aim to test the effectiveness of an online self-management programme (BOOST), developed using cognitive behavioural principles and a theoretically informed logic model, and delivered with facilitator support.

Primary Research Question: In people with IBD who report symptoms of fatigue, pain or urgency and express a desire for intervention, does a facilitator-supported tailored (to patient needs) online self-management programme for fatigue, pain and faecal urgency/incontinence improve IBD-related quality of life (measured using the UK-IBDQ) and global rating of symptom relief (0-10 scale) compared with care as usual?

Methods: A pragmatic two-arm, parallel group randomised controlled trial (RCT), of a 12-session facilitator-supported online cognitive behavioural self-management programme versus care as usual to manage symptoms of fatigue, pain and faecal urgency/incontinence in IBD. Patients will be recruited through a previous large-scale survey of unselected people with inflammatory bowel disease. The UK Inflammatory Bowel Disease Questionnaire and global rating of symptom relief at 6 months are the co-primary outcomes, with multiple secondary outcomes measured also at 6 and 12 months post randomisation to assess maintenance. The RCT has an embedded pilot study, health economics evaluation and process evaluation. We will randomise 680 patients, 340 in each group. Demographic characteristics and outcome measures will be presented for both study groups at baseline. The UK-IBDQ and global rating of symptom relief at 6 and 12 months post randomisation will be compared between the study groups.

Discussion: The BOOST online self-management programme for people with IBD-related symptoms of fatigue, pain and urgency has been designed to be easily scalable and implemented. If it is shown to improve patients' quality of life, this trial will enable clinicians and patients to make informed management decisions. This is the first trial, to our knowledge, focused on multiple symptoms prioritised by both people with IBD and health professionals.

Trial Registration: ISRCTN71618461 . Registered on 9 September 2019.
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http://dx.doi.org/10.1186/s13063-021-05466-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329619PMC
August 2021

Prospective randomised controlled trial of adults with perianal fistulising Crohn's disease and optimised therapeutic infliximab levels: PROACTIVE trial study protocol.

BMJ Open 2021 07 1;11(7):e043921. Epub 2021 Jul 1.

South Western Sydney Clinical School, University of New South Wales, Sydney, New South Wales, Australia

Introduction: Perianal fistulising Crohn's disease (pfCD) can be somewhat treatment refractory. Higher infliximab trough levels (TLIs) may improve fistula healing rates; however, it remains unclear whether escalating infliximab therapy to meet higher TLI targets using proactive, or routine, therapeutic drug monitoring (TDM) improves outcomes. This randomised controlled trial aimed to assess whether infliximab therapy targeting higher TLIs guided by proactive TDM improves outcomes compared with standard therapy.

Methods And Analysis: Patients with active pfCD will be randomised 1:1 to either the proactive TDM arm or standard dosing arm and followed up for 54 weeks. Patients in the proactive TDM arm will have infliximab dosing optimised to target higher TLIs. The targets will be TLI ≥ 25 µg/mL at week 2, ≥ 20 µg/mL at week 6 and ≥ 10 µg/mL during maintenance therapy. The primary objective will be fistula healing at week 32. Secondary objectives will include fistula healing, fistula closure, radiological fistula healing, patient-reported outcomes and economic costs up to 54 weeks. Patients in the standard dosing arm will receive conventional infliximab dosing not guided by TLIs (5 mg/kg at weeks 0, 2 and 6, and 5 mg/kg 8 weekly thereafter). Patients aged 18-80 years with pfCD with single or multiple externally draining complex perianal fistulas who are relatively naïve to infliximab treatment will be included. Patients with diverting ileostomies or colostomies and pregnant or breast feeding will be excluded. Fifty-eight patients per arm will be required to detect a 25% difference in the primary outcome measure, with 138 patients needed to account for an estimated 6.1% primary non-response rate and 10% dropout rate.

Ethics And Dissemination: Results will be presented in peer-reviewed journals and international conferences. Ethics approval has been granted by the South Western Sydney Local Health District Human Research Ethics Committee in Australia.

Trial Registration Number: Australian New Zealand Clinical Trials Registry (ACTRN12621000023853); Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2020-043921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252869PMC
July 2021

Predicting Colorectal Cancer Occurrence in IBD.

Cancers (Basel) 2021 Jun 10;13(12). Epub 2021 Jun 10.

Inflammatory Bowel Disease Department, St. Mark's Hospital, Watford R.d., Harrow HA1 3UJ, UK.

Patients with colonic inflammatory bowel disease (IBD) are at an increased risk of developing colorectal cancer (CRC), and are therefore enrolled into a surveillance programme aimed at detecting dysplasia or early cancer. Current surveillance programmes are guided by clinical, endoscopic or histological predictors of colitis-associated CRC (CA-CRC). We have seen great progress in our understanding of these predictors of disease progression, and advances in endoscopic technique and management, along with improved medical care, has been mirrored by the falling incidence of CA-CRC over the last 50 years. However, more could be done to improve our molecular understanding of CA-CRC progression and enable better risk stratification for patients with IBD. This review summarises the known risk factors associated with CA-CRC and explores the molecular landscape that has the potential to complement and optimise the existing IBD surveillance programme.
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http://dx.doi.org/10.3390/cancers13122908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230430PMC
June 2021

Long-term outcome and quality of life after continent ileostomy for ulcerative colitis: A systematic review.

Colorectal Dis 2021 Sep 18;23(9):2286-2299. Epub 2021 Jul 18.

St Mark's Hospital and Academic Institute, Harrow, UK.

Aim: The continent ileostomy allows evacuation of an ileal reservoir at a time convenient to the patient. It is a surgical option for patients with ulcerative colitis (UC) when a restorative option is not suitable or has not succeeded and the patient does not want a conventional end ileostomy. Continent ileostomy types include the Kock pouch, Barnett continent intestinal reservoir and T-pouch. All of the published evidence on the long-term outcome and quality of life after continent ileostomy for UC was systematically reviewed.

Methods: A systematic review was performed in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies published between 1990 and 2020 were included. A descriptive synthesis was used due to the clinical heterogeneity.

Results: The search returned 1655 abstracts and after screening of abstracts and full text review, 19 were included in the final review, involving 1602 patients. Operative mortality is low (0%-3.6%) after all types of continent ileostomy but reoperation rates are high (20.8%-65%) because of valve mechanism failures. Rates of fistulae (0%-25.5%) and stomal stenosis (0%-25%) can be relatively high postoperatively. Quality of life scores improve for most patients undergoing continent ileostomy, especially for patients converted from ileal pouch anal anastomosis. Overall, continent ileostomy retention is high in the long-term.

Discussion: In the long-term, patients report high satisfaction and a good quality of life with continent ileostomy, despite high reoperation rates and complications. Newer technologies may reinvigorate interest in the continent ileostomy for this population.
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http://dx.doi.org/10.1111/codi.15788DOI Listing
September 2021

Perception of cancer risk and management practice for colitis-associated dysplasia is influenced by colonoscopy experience and workplace results of an international clinician survey.

J Crohns Colitis 2021 Jun 22. Epub 2021 Jun 22.

Imperial College London, UK.

Background And Aims: A successful colitis cancer surveillance programme requires effective action to be taken when dysplasia is detected. This is the first international cross-sectional study to evaluate clinician understanding of dysplasia-cancer risk and management practice since the most recent international guidelines were introduced in 2015.

Methods: A 15-item international online survey was disseminated to gastroenterologists and colorectal surgeons.

Results: 294 clinicians (93.5% gastroenterologists) from 60 countries responded. Twenty-three percent did not have access to high-definition chromoendoscopy. University hospitals were more likely than non-academic workplaces to provide second expert histopathologist review (67% vs. 46%; p=0.002) and formal multidisciplinary team meeting discussion (73% vs. 52%; p=0.001) of dysplasia cases. Perceptions of 5-year cancer risk associated with endoscopically unresectable low-grade dysplasia varied between 0 - 100%. Non-academic hospital affiliation was predictive of lower perceived cancer risks. Although most (98.4%) respondents advised a colectomy for endoscopically unresectable visible high-grade dysplasia, only 34.4% advised a colectomy for unresectable visible low-grade dysplasia. Respondents from university hospitals were more likely to consider colectomy for multifocal low-grade dysplasia [OR 2.17]. If invisible unifocal low-grade dysplasia was detected, continued surveillance over colectomy was the preferred management amongst clinicians working mainly in private clinics [OR 9.4] and least preferred in those who had performed more than 50 surveillance colonoscopies [OR 0.41].

Conclusions: Clinicians with less surveillance colonoscopy experience and from non-academic centres appear to have lower cancer risk perceptions and are less likely to advocate colectomy for higher-risk low-grade dysplasia. Further education may align current management practice with clinical guidelines.
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http://dx.doi.org/10.1093/ecco-jcc/jjab110DOI Listing
June 2021

The Microbiome as a Therapy in Pouchitis and Ulcerative Colitis.

Nutrients 2021 May 23;13(6). Epub 2021 May 23.

Inflammatory Bowel Disease Unit, St. Mark's Hospital, Harrow HA1 3UJ, UK.

The gut microbiome has been implicated in a range of diseases and there is a rapidly growing understanding of this ecosystem's importance in inflammatory bowel disease. We are yet to identify a single microbe that causes either ulcerative colitis (UC) or pouchitis, however, reduced microbiome diversity is increasingly recognised in active UC. Manipulating the gut microbiome through dietary interventions, prebiotic and probiotic compounds and faecal microbiota transplantation may expand the therapeutic landscape in UC. Specific diets, such as the Mediterranean diet or diet rich in omega-3 fatty acids, may reduce intestinal inflammation or potentially reduce the risk of incident UC. This review summarises our knowledge of gut microbiome therapies in UC and pouchitis.
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http://dx.doi.org/10.3390/nu13061780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224581PMC
May 2021

Prognostic factors associated with unhealed perineal wounds post-proctectomy for perianal Crohn's disease: a two-centre study.

Colorectal Dis 2021 Aug 8;23(8):2091-2099. Epub 2021 Jun 8.

St Mark's Hospital, Harrow, UK.

Aim: The aim of this work was to determine the factors associated with poor wound healing in patients with perianal Crohn's disease (pCD) who had undergone proctectomy in the era of biologic therapies.

Method: Case record review was performed on 103 patients with pCD who underwent proctectomy at St Mark's Hospital, Harrow and the Western General Hospital, Edinburgh between 2005 and 2017. Healing rates at 6 and 12 months post-proctectomy were considered; univariate analysis was performed.

Results: Sixty out of 103 patients (58.3%) had failure of wound healing at 6 months and 41/103 (39.8%) at 12 months. In total, 63.1% (65/103) patients received biologic therapies prior to proctectomy; however, exposure to biologics was not a significant factor in predicting failure of wound healing at 12 months (infliximab p = 0.255; adalimumab p = 0.889; vedolizumab p = 0.153). Male gender was the only variable associated with poor wound healing at 12 months on univariate analysis (p = 0.017). A lower pre-operative C-reactive protein was associated with early wound healing at 6 months compared with at 12 months (p = 0.041) on univariate analysis. Other parameters not associated with rates of wound healing included smoking status, corticosteroid exposure, thiopurine exposure, number of previous biologics, perianal sepsis on MRI within the last 12 months, duration of CD prior to proctectomy and pre-operative albumin.

Conclusion: More than a third of patients had unhealed wounds 12 months after proctectomy. We report that unhealed wounds are more common in male patients. Importantly, our results also suggest that exposure to biologics does not affect rates of wound healing.
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http://dx.doi.org/10.1111/codi.15744DOI Listing
August 2021

Multicentre derivation and validation of a colitis-associated colorectal cancer risk prediction web tool.

Gut 2021 May 14. Epub 2021 May 14.

Department of Gastroenterology, St Mark's Hospital and Academic Institute, London, UK.

Objective: Patients with ulcerative colitis (UC) diagnosed with low-grade dysplasia (LGD) have increased risk of developing advanced neoplasia (AN: high-grade dysplasia or colorectal cancer). We aimed to develop and validate a predictor of AN risk in patients with UC with LGD and create a visual web tool to effectively communicate the risk.

Design: In our retrospective multicentre validated cohort study, adult patients with UC with an index diagnosis of LGD, identified from four UK centres between 2001 and 2019, were followed until progression to AN. In the discovery cohort (n=246), a multivariate risk prediction model was derived from clinicopathological features using Cox regression. Validation used data from three external centres (n=198). The validated model was embedded in a web tool to calculate patient-specific risk.

Results: Four clinicopathological variables were significantly associated with AN progression in the discovery cohort: endoscopically visible LGD >1 cm (HR 2.7; 95% CI 1.2 to 5.9), unresectable or incomplete endoscopic resection (HR 3.4; 95% CI 1.6 to 7.4), moderate/severe histological inflammation within 5 years of LGD diagnosis (HR 3.1; 95% CI 1.5 to 6.7) and multifocality (HR 2.9; 95% CI 1.3 to 6.2). In the validation cohort, this four-variable model accurately predicted future AN cases with overall calibration Observed/Expected=1.01 (95% CI 0.64 to 1.52), and achieved 100% specificity for the lowest risk group over 13 years of available follow-up.

Conclusion: Multicohort validation confirms that patients with large, unresected, multifocal LGD and recent moderate/severe inflammation are at highest risk of developing AN. Personalised risk prediction provided via the Ulcerative Colitis-Cancer Risk Estimator () can support treatment decision-making.
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http://dx.doi.org/10.1136/gutjnl-2020-323546DOI Listing
May 2021

Biobetters in patients with immune-mediated inflammatory disorders: An international Delphi consensus.

Autoimmun Rev 2021 Jul 8;20(7):102849. Epub 2021 May 8.

Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; IBD center, Humanitas Research Hospital, IRCCS, Rozzano, Milan, Italy. Electronic address:

Several efforts have been made to improve the available therapeutic armamentarium of patients with immune-mediated inflammatory disorders (IMIDs) leading to the development of biobetters. To date, there is no commonly accepted definition of biobetters. Sixteen physicians with expertise in the field of IMIDs from eleven countries attended a virtual international consensus meeting to provide for the first time a definition of biobetter and to identify unmet needs on this topic. Improvements in clinical outcomes and drug pharmacology were considered crucial for the definition of biobetters, while safety profile and patient acceptability were not. In addition, an appropriate balance between clinical outcomes and costs and a shared decision between physicians and patients should guide the decision to use a biobetter. Clinical studies are required to validate the biobetter definition and to investigate their role in the management of patients with IMIDs.
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http://dx.doi.org/10.1016/j.autrev.2021.102849DOI Listing
July 2021

Ulcerative colitis: an update.

Clin Med (Lond) 2021 03;21(2):135-139

St Mark's Hospital, Harrow, UK and Imperial College London, London, UK.

Ulcerative colitis is a relapsing and remitting disease that is increasing in incidence and prevalence. Management aims to achieve rapid resolution of symptoms, mucosal healing and improvement in a patient's quality of life. 5-aminosalicylate acid medications remain the first-line treatment for mild to moderate disease. In the event of suboptimal response to these medications, escalation to immunosuppressive medications and biologics may be necessary. Importantly, despite best medical therapy, surgery may be required in a proportion of patients. The future will likely see an array of new therapeutic options for those with ulcerative colitis with the potential for a more personalised treatment approach.
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http://dx.doi.org/10.7861/clinmed.2021-0080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002778PMC
March 2021

Anti-SARS-CoV-2 antibody responses are attenuated in patients with IBD treated with infliximab.

Gut 2021 05 22;70(5):865-875. Epub 2021 Mar 22.

Division of Digestive Diseases, Faculty of Medicine, Imperial College London, London, UK.

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 public health policy.

Trial Registration Number: ISRCTN45176516.
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http://dx.doi.org/10.1136/gutjnl-2021-324388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992387PMC
May 2021

Squamous cell carcinoma at the site of ileo-anal pouch in Crohn's disease.

BMJ Case Rep 2021 Feb 8;14(2). Epub 2021 Feb 8.

St Mark's Hospital Foundation, Harrow, London, UK.

Few cases of pouch-related cancers have been reported in inflammatory bowel disease, and squamous cell carcinoma (SCC) is very rare. We have reviewed the published literature searching the online databases PubMed and Medline. Since 1979, there have been eight cases of SCC developing after restorative proctocolectomy in ulcerative colitis. To date, there have been no reported cases of SCC of the ileo-anal pouch in Crohn's disease. We present the case of a 59-year-old woman who underwent colectomy with ileal pouch-anal anastomosis for Crohn's disease during the 1990s. The patient was noted to be anaemic and was experiencing significant weight loss with poor pouch function in 2019. Endoscopy with histology and radiological investigation revealed the presence of SCC of the pouch. This was subsequently treated with surgical therapy and chemoradiotherapy.
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http://dx.doi.org/10.1136/bcr-2020-237438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872916PMC
February 2021

The pouch behaving badly: management of morbidity after ileal pouch-anal anastomosis.

Colorectal Dis 2021 May 15;23(5):1193-1204. Epub 2021 Feb 15.

St Mark's Hospital, Harrow, Middlesex, UK.

Aim: Ileal pouch-anal anastomosis (IPAA), or a 'pouch', allows restoration of intestinal continuity after proctocolectomy for ulcerative colitis or familial adenomatous polyposis. Most patients have a good long-term outcome after IPAA, but in a significant proportion the functional outcome and quality of life are unsatisfactory. We term this outcome 'the pouch behaving badly'. Managing this, especially one is when unfamiliar with the possible underlying pathologies, is a challenge for both patient and clinician. We aim to outline the clinical approach to the pouch behaving badly, highlighting key aspects of investigation and management.

Method: This is a narrative review of the literature covering the investigation and management of postoperative complications and morbidity after IPAA.

Results: Management of the pouch behaving badly requires a careful clinical assessment. The patient may present with multiple symptoms and a clear picture of the symptomatology and past history should be constructed before thorough examination and specialist investigation. We divide the pathology that underlies this clinical scenario into surgical, inflammatory, mechanical, functional and dysplastic causes and outline the investigation and management of each one.

Conclusion: The pouch behaving badly is a challenging problem for both patient and clinician. A detailed clinical assessment with careful specialist investigation is key to diagnosing the underlying pathology. We stress the importance of patient-centred care - the aim is to improve quality of life.
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http://dx.doi.org/10.1111/codi.15553DOI Listing
May 2021

Lack of anti-TNF drugs levels in fistula tissue - a reason for nonresponse in Crohn's perianal fistulating disease?

Eur J Gastroenterol Hepatol 2021 Jan 14. Epub 2021 Jan 14.

aRobin Phillips Fistula Research Unit, St Mark's Hospital & Academic Institute, Harrow, Middlesex bDepartment of Surgery and Cancer, Imperial College London cComputational Systems Division, Imperial College London, South Kensington Campus dBlizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

Introduction: Anti-TNF therapy is recommended as treatment for patients with Crohn´s perianal fistulas. However, a significant proportion of patients have a sub-optimal response to anti-TNF therapy. Higher serum levels of anti-TNF agents have been associated with improved outcomes in perianal Crohn's disease. Currently, it is unknown whether anti-TNF agent levels can be detected in tissue from fistula tracts themselves and whether this is associated with response.

Aims And Methods: We undertook a pilot study to measure fistula tissue levels of anti-TNF medication (infliximab and adalimumab). We used a previously validated targeted proteomic technique, employing ultraperformance liquid chromatography-mass spectrometry, to detect/quantify anti-TNF drugs. Biopsies were obtained from fistula tracts of patients with Crohn's disease on maintenance treatment; with idiopathic (cryptoglandular) fistula tissues used as negative controls as well as positive controls (by spiking the latter tissues with anti-TNF drugs).

Results: Tissue was sampled from the fistula tracts of seven patients with Crohn's perianal disease (five patients were on adalimumab and two patients were on infliximab). The anti-TNF drugs, infliximab and adalimumab, were not detected in fistula samples from any of the Crohn's patients despite detection in 'spiked' positive control samples.

Conclusion: Absence of detection of the anti-TNF drugs in fistula tissue raises the question on the role of tissue penetrance of anti-TNF drugs in response to therapy. Further work is required in a larger number of patients to validate the findings observed and investigate if any correlation exists between tissue and serum levels of anti-TNF and clinical outcome.

Summary: Predicting response in Crohn's fistula patients on biologic therapy is difficult with no reliable biomarkers. This pilot study uses targeted proteomics to investigate the potential role of tissue drug levels in acting as a biomarker of treatment response.
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http://dx.doi.org/10.1097/MEG.0000000000002032DOI Listing
January 2021

International Perspectives on Management of Inflammatory Bowel Disease: Opinion Differences and Similarities Between Patients and Physicians From the IBD GAPPS Survey.

Inflamm Bowel Dis 2021 Jan 29. Epub 2021 Jan 29.

The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.

Background: Inflammatory bowel diseases (IBD), including Crohn disease (CD) and ulcerative colitis (UC), are complex disorders with multiple comorbidities. We conducted international patient and physician surveys to evaluate current experiences and perceptions of patients with CD or UC and physicians who treat IBD.

Methods: The IBD Global Assessment of Patient and Physician Unmet Need Surveys comprised a patient survey and a physician survey, fielded in North America and Europe between August 16, 2019, and November 10, 2019. Adults with CD or UC (targeted 1:1 ratio) were recruited from physicians, patient advocacy groups, and recruitment panels; physicians were recruited by recruitment agencies and panels.

Results: In total, 2398 patients with IBD (1368 CD, 1030 UC) and 654 physicians completed surveys. Anxiety and depression were the most common comorbidities among patients with IBD. Patients and physicians were generally aligned on treatment goals and patient-physician communication. Patients with IBD reported high quality-of-life impact by rectal urgency and need to use the toilet, which were rated as lower-impact by physicians. Patients defined remission based on symptoms; physicians defined remission based primarily on clinical tests. Patients expected current treatments to control their disease for a longer duration than did physicians. Patients expressed more concern about corticosteroid use compared with physicians; many physicians reported prescribing corticosteroids for more than 4 months per year in some patients.

Conclusions: Patients could benefit from education about disease remission and expectations for current therapies. High corticosteroid use is concerning to patients, and physicians should minimize the use of corticosteroids for extended periods of time.
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http://dx.doi.org/10.1093/ibd/izab006DOI Listing
January 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 Gastroenterol Hepatol 2021 03 26;6(3):218-224. Epub 2021 Jan 26.

Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK; Department of Gastroenterology, Imperial College Healthcare NHS Trust, London, UK. Electronic address:

SARS-CoV-2 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 (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-CoV-2 vaccination strategy in patients with IBD. The risks of SARS-CoV-2 vaccination are anticipated to be very low, and we strongly support SARS-CoV-2 vaccination in patients with IBD. Based on data from previous studies with other vaccines, there are conceptual concerns that protective immune responses to SARS-CoV-2 vaccination may be diminished in some patients with IBD, such as those taking anti-TNF drugs. However, the benefits of vaccination, even in patients treated with anti-TNF drugs, 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 effect of immunosuppression on vaccine efficacy, and the search for predictive biomarkers of vaccine success.
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http://dx.doi.org/10.1016/S2468-1253(21)00024-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834976PMC
March 2021

Editorial: a pipe dream fulfilled? A therapeutic option for fatigue in IBD.

Aliment Pharmacol Ther 2021 01;53(2):342-343

St Mark's Hospital, IBD Unit, Harrow, UK.

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http://dx.doi.org/10.1111/apt.16185DOI Listing
January 2021

Differences in amino acid and lipid metabolism distinguish Crohn's from idiopathic/cryptoglandular perianal fistulas by tissue metabonomic profiling and may offer clues to underlying pathogenesis.

Eur J Gastroenterol Hepatol 2020 Dec 18;Publish Ahead of Print. Epub 2020 Dec 18.

Robin Phillips Fistula Research Unit, St Mark's Hospital and Academic Institute, Harrow, Middlesex Department of Surgery and Cancer Computational Systems Division, Imperial College London, South Kensington Campus, London, UK Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia.

Introduction: Few studies have investigated perianal fistula etiopathogenesis, and although the cryptoglandular theory is widely accepted in idiopathic cases, in Crohn's disease, it is thought to involve the interplay between microbiological, immunological and genetic factors. A pilot study was conducted to assess for metabolic variations in Crohn's perianal fistula tissue that might differ from that of idiopathic (cryptoglandular) perianal fistula tissue as a comparator. The goal was to identify any potential biomarkers of disease, which may improve the understanding of pathogenesis.

Aims And Methods: Fistula tract biopsies were obtained from 30 patients with idiopathic perianal fistula and 20 patients with Crohn's anal fistula. Two different assays were used in an ultra-high-performance liquid chromatography system coupled with a mass spectrometric detector to achieve broad metabolome coverage. Univariate and multivariate statistical data analyses were used to identify differentiating metabolic features corresponding to the perianal fistula phenotype (i.e. Crohn's disease vs. idiopathic).

Results: Significant orthogonal partial least squares discriminant analysis predictive models (validated with cross-validated-analysis of variance P value <0.05) differentiated metabolites from tissue samples from Crohn's vs. idiopathic anal fistula patients using both metabolic profiling platforms. A total of 41 metabolites were identified, suggesting alterations in pathways, including amino acid, carnitine and lipid metabolism.

Conclusion: Metabonomics may reveal biomarkers of Crohn's perianal fistula. Further work in larger numbers is required to validate the findings of these studies as well as cross-correlation with microbiome work to better understand the impact of host-gut/environment interactions in the pathophysiology of Crohn's and idiopathic perianal fistulas and identify novel therapeutic targets.
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http://dx.doi.org/10.1097/MEG.0000000000001976DOI Listing
December 2020

Development and initial psychometric validation of a patient-reported outcome measure for Crohn's perianal fistula: the Crohn's Anal Fistula Quality of Life (CAF-QoL) scale.

Gut 2021 Sep 3;70(9):1649-1656. Epub 2020 Dec 3.

Surgery and Cancer, Imperial College London, London, UK.

Introduction: Crohn's perianal fistulas are challenging for patients and clinicians. Many do not respond to available treatments and despite recommendations by a global consensus, there are currently no specific patient-derived quality of life tools to measure response to treatment. We present a new validated patient-reported outcome measure (PROM) for this complicated disease phenotype.

Methods: A draft questionnaire was generated using unstructured qualitative patient interviews on the experience of living with Crohn's perianal fistula, a nationwide multidisciplinary consensus exercise, a systematic review of outcomes assessing medical/surgical/combined treatment and a patient and public involvement day. Psychometric properties were assessed including construct validity (by comparison with the Hospital Anxiety and Depression Scale (HADS) and the UK Inflammatory Bowel Disease Questionnaire (UK-IBDQ)), and reliability and responsiveness was assessed by test-retest analysis.

Results: Data from 211 patients contributed to development of a final 28-item questionnaire. The Crohn's Anal Fistula Quality of Life (CAF-QoL) demonstrated good internal consistency (Cronbach's alpha 0.88), excellent stability (intraclass correlation 0.98) and good responsiveness and construct validity, with positive correlation with the UK-IBDQ and HADS.

Conclusion: The CAF-QoL scale is ready for use as a PROM in research and clinical practice. It complements objective clinical evaluation of fistula by capturing impact on the patient.
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http://dx.doi.org/10.1136/gutjnl-2019-320553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355881PMC
September 2021

Management of inflammatory bowel disease associated colonic dysplasia: factors predictive of patient choice and satisfaction.

Colorectal Dis 2021 Apr 19;23(4):882-893. Epub 2020 Dec 19.

Imperial College London, London, UK.

Aim: In cases of prognostic uncertainty and equipoise as to the best management (prophylactic colectomy vs. surveillance) for dysplasia in inflammatory bowel disease (IBD), individualized discussion with the patient is required. Further understanding of patients' preferences is needed.

Methods: A nationwide cross-sectional survey was distributed to adult IBD patients who had never been diagnosed with dysplasia (dysplasia-naïve) and those who had (dysplasia-experienced). Risk perceptions and factors that influence management choices were explored.

Results: There were 123 respondents. A substantial proportion (29%) of the dysplasia-experienced respondents did not feel well informed about the associated cancer risk and/or its management by their clinical team. Contributing themes included contradictory advice and lack of personalized information regarding their cancer risk, alternative management options and impact on long-term quality of life. Decisional regret and health-related quality of life amongst those who chose either surveillance or surgery were comparable, but cancer-related worry scores were elevated in the surveillance group. The dysplasia-naïve respondents reported that they would only consider having a prophylactic colectomy if they had on average a 50% or even higher risk of developing cancer. On multivariable logistic regression analyses, predictors of colectomy or surveillance preference included ethnicity, personality traits such as health locus of control (whether health status is influenced by luck) and differences in perception of what a low risk of cancer is.

Conclusions: This study identifies predictive factors that can influence decision-making and satisfaction with the counselling process when IBD dysplasia is diagnosed. Further qualitative exploration of cultural themes would be informative.
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http://dx.doi.org/10.1111/codi.15460DOI Listing
April 2021

Burden of disease and adaptation to life in patients with Crohn's perianal fistula: a qualitative exploration.

Health Qual Life Outcomes 2020 Nov 20;18(1):370. Epub 2020 Nov 20.

Robin Phillips Fistula Research Unit, St Mark's Hospital and Academic Institute, Watford Road, Harrow, HA1 3UJ, Middlesex, UK.

Background: Perianal fistulas are a challenging manifestation of Crohn's disease. Best medical and surgical therapy results in only about a third of patients remaining in remission at one year on maintenance treatment and sustained healing is often elusive. There is little published data on patient perspective of living with the condition or coping strategies in the face of non-curative/non-definitive treatment. We aimed to understand the experience of living with perianal fistula(s) and their impact on quality of life and routine functioning.

Methods: This exploratory qualitative study used purposive sampling to recruit participants with current / previous diagnosis of Crohn's anal fistulas, from national IBD / bowel disease charities. The "standards for reporting qualitative research" (SRQR) recommendations were followed. Unstructured individual face-to-face interviews were audio recorded, transcribed and analysed thematically. Early themes were reviewed by the study team including patient advocates, clinicians and qualitative researchers.

Results: Twelve interviews were conducted, achieving apparent data saturation. Three broad themes were uncovered: Burden of symptoms; Burden of treatment; and Impact on emotional, physical and social well-being. Each included several sub-themes, with considerable interplay between these. The impact of perianal fistula(s) on patients with CD is intense and wide reaching, negatively affecting intimate, close and social relationships. Fistulas cause losses in life and work-related opportunities, and treatments can be difficult to tolerate.

Conclusion: Crohn's perianal fistulas exert a heavy negative physical and emotional impact on patients. These findings will inform development of a patient reported outcome measure to assess treatment effectiveness and quality of life for patients living with this challenging condition.
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http://dx.doi.org/10.1186/s12955-020-01622-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678264PMC
November 2020

International Organization for the Study of Inflammatory Bowel Disease: Global Strategies for Telemedicine and Inflammatory Bowel Diseases.

J Crohns Colitis 2020 Oct;14(14 Suppl 3):S780-S784

Division of Gastroenterology, University of California, San Francisco, CA, USA.

Before the onset of the COVID-19 pandemic, the majority of care for inflammatory bowel disease patients was provided in-person. The practice of gastroenterology care has since rapidly transformed, with telemedicine emerging as an essential tool to provide medical care to patients while maintaining social distancing and conserving personal protective equipment. This article provides insight into past and current practices among inflammatory bowel disease specialists and shares regulatory, financial and practical considerations for incorporating telemedicine into clinical practice. Continued government and other payer support for telemedicine and ongoing innovation to provide remote objective patient data will help to sustain the use of telemedicine long after the current pandemic subsides.
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http://dx.doi.org/10.1093/ecco-jcc/jjaa140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665391PMC
October 2020

Precision Medicine with FMT for Ulcerative Colitis: Are We There Yet?

J Crohns Colitis 2021 Apr;15(4):519-520

Department of Gastroenterology, St Marks Hospital, London, UK.

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http://dx.doi.org/10.1093/ecco-jcc/jjaa190DOI Listing
April 2021

Ulcerative Colitis Narrative Global Survey Findings: Communication Gaps and Agreements Between Patients and Physicians.

Inflamm Bowel Dis 2021 06;27(7):1096-1106

Department of Internal Medicine, University Hospital Schleswig-Holstein, Kiel, Germany.

Background: The Ulcerative Colitis (UC) Narrative global surveys examined patient and physician perspectives on living with UC and tried to identify gaps in optimal care. Questions explored patient-physician interactions, UC management goals, and resources for improving communication.

Methods: Questionnaires were conducted across 10 countries, covering aspects of UC including diagnosis, treatment, and impact on patient quality of life, in addition to standard demographic information. Descriptive statistics were calculated.

Results: Globally, 2100 patients and 1254 physicians were surveyed (from August 2017 to February 2018). Results showed 85% of patients were satisfied with the communication they had with their physician, including discussions relating to symptoms (86%) and medication options (81%). However, 72% of patients wished for more information and support at initial diagnosis, and 48% did not feel comfortable talking to their physician about emotional concerns. Most patients (71%) set UC management goals with their physician. Both patients (63%) and physicians (79%) wished for longer appointments. Although 84% of physicians believed patient advocacy organizations to be important in UC management, more than half (54%) never discussed them with patients.

Conclusions: These survey results highlight overall patient satisfaction with patient-physician communication but emphasize areas for improvement, such as patient desire to have more information earlier in their disease course. There is an unmet need for better information, materials, and support. Physicians need to consider which of the available tools and resources can help patients talk more openly, and accurately, because informed patients are more likely to engage with physicians in a shared decision-making process.
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http://dx.doi.org/10.1093/ibd/izaa257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214018PMC
June 2021

Multiomic features associated with mucosal healing and inflammation in paediatric Crohn's disease.

Aliment Pharmacol Ther 2020 11 14;52(9):1491-1502. Epub 2020 Sep 14.

Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK.

Background: The gastrointestinal microbiota has an important role in mucosal immune homoeostasis and may contribute to maintaining mucosal healing in Crohn's disease (CD).

Aim: To identify changes in the microbiota, metabolome and protease activity associated with mucosal healing in established paediatric CD METHODS: Twenty-five participants aged 3-18 years with CD, disease duration of over 6 months, and maintenance treatment with biological therapy were recruited. They were divided into a low calprotectin group (faecal calprotectin <100 μg/g, "mucosal healing," n = 11), and a high calprotectin group (faecal calprotectin >100 μg/g, "mucosal inflammation," n = 11). 16S gene-based metataxonomics, H-NMR spectroscopy-based metabolic profiling and protease activity assays were performed on stool samples.

Results: Relative abundance of Dialister species was six-times greater in the low calprotectin group (q = 0.00999). Alpha and beta diversity, total protease activity and inferred metagenomic profiles did not differ between groups. Pentanoate (valerate) and lysine were principal discriminators in a machine-learning model which differentiated high and low calprotectin samples using NMR spectra (R 0.87, Q 0.41). Mean relative concentration of pentanoate was 1.35-times greater in the low calprotectin group (95% CI 1.03-1.68, P = 0.036) and was positively correlated with Dialister. Mean relative concentration of lysine was 1.54-times greater in the high calprotectin group (95% CI 1.05-2.03, P = 0.028).

Conclusions: This multiomic study identified an increase in Dialister species and pentanoate, and a decrease in lysine, in patients with "mucosal healing." It supports further investigation of these as potential novel therapeutic targets in CD.
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http://dx.doi.org/10.1111/apt.16086DOI Listing
November 2020

The use of 5-aminosalicylates in Crohn's disease: a retrospective study using the UK Clinical Practice Research Datalink.

Ann Gastroenterol 2020 Sep-Oct;33(5):500-507. Epub 2020 Jun 22.

Institute of Immunology and Immunotherapy, University of Birmingham, UK (Subrata Ghosh).

Background: There are few recent studies on the use of 5-aminosalicylates (5-ASA) as therapy for Crohn's disease (CD) in routine clinical practice. The aim of this database investigation was to provide real-world evidence on 5-ASA use in CD.

Methods: Patients with CD, aged ≥18 years when first prescribed 5-ASA (index date) and having received 5-ASA at any time between 01 January 2006 and 07 May 2018, were included for analysis. Outcomes included treatment patterns and resource use.

Results: Of 21,456 patients with CD, 9492 (44.2%) had been prescribed 5-ASA, with the majority (5606; 59.1%) starting on oral 5-ASA as monotherapy. 58.3% (5537) of patients on 5-ASA did not require dose change, 67.6% (6416) did not require supplementary treatment (e.g., corticosteroids, immunosuppressants, etc.), and 4.6% (436) required a switch to another treatment. Resource use was significantly decreased in the year after vs. year before 5-ASA initiation (including: specialist referrals, hospitalizations and hospital days; all P<0.001). Patients remained on 5-ASA for a median of 4.7 years (interquartile range 1.2-10.1). 25.3% (2406) of patients were still on 5-ASA at 10 years. There was a significant correlation between earlier use of 5-ASA following diagnosis and longer 5-ASA retention (P<0.001).

Conclusions: 5-ASA is widely used as a long-term treatment for CD, as evidenced by continuation rates extending beyond 10 years in a quarter of patients. CD-related healthcare resource use decreased significantly in the year following 5-ASA initiation. Earlier use was associated with longer retention.
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http://dx.doi.org/10.20524/aog.2020.0521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406809PMC
June 2020

Randomized Trial of Ciprofloxacin Doxycycline and Hydroxychloroquine Versus Budesonide in Active Crohn's Disease.

Dig Dis Sci 2021 08 17;66(8):2700-2711. Epub 2020 Jul 17.

Henry Wellcome Laboratory, Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, Royal Liverpool University Hospital, University of Liverpool, Nuffield Building, Crown Street, Liverpool, L69 3GE, UK.

Background: Increased mucosa-associated E. coli are present in Crohn's disease, but their role in pathogenesis is uncertain.

Aims: To assess efficacy and safety of an antibiotic/hydroxychloroquine combination effective against E. coli inside macrophages.

Methods: Adults with moderately active disease (CDAI > 220-450 plus C reactive protein ≥ 5 mg/l and/or fecal calprotectin > 250 μg/g) were randomized to receive (open-label) oral budesonide (Entocort CR 9 mg/day 8 weeks, 6 mg/day 2 weeks, 3 mg/day 2 weeks) or oral ciprofloxacin 500 mg bd, doxycycline 100 mg bd, hydroxychloroquine 200 mg tds for 4 weeks, followed by doxycycline 100 mg bd and hydroxychloroquine 200 mg tds for 20 weeks. Primary endpoints were remission (CDAI ≤ 150) at 10 weeks, remission maintained to 24 weeks, and remission maintained to 52 weeks. Patients not responding (CDAI fall by > 70) by 10 weeks were invited to crossover onto the alternative therapy.

Results: Fifty-nine patients were recruited across 8 sites. Including crossover, 39 patients received antibiotics/hydroxychloroquine and 39 received budesonide. At 10 weeks, 24 weeks, and 52 weeks on initial therapy, only 2/27, 2/27, and 1/27 were in remission on antibiotics/hydroxychloroquine compared with 8/32, 1/32, and 1/32 on budesonide (P = 0.092 at 10 weeks). Withdrawals by 10 weeks due to adverse events were seen in 15 receiving antibiotics/hydroxychloroquine and 6 budesonide. Results including crossover were more promising with 9/24 patients receiving antibiotics/hydroxychloroquine per protocol in remission by 24 weeks. No correlation was seen between response to antibiotics/hydroxychloroquine and ASCA/OmpC antibody status or disease location.

Conclusion: Overall results with this antibiotic/hydroxychloroquine combination were unimpressive, but long-term remission is seen in some patients and justifies further study.
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http://dx.doi.org/10.1007/s10620-020-06477-yDOI Listing
August 2021
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