X Chromosome Contribution to the Genetic Architecture of Primary Biliary Cholangitis (2021)

Type of publication:
Journal article

Author(s):
Asselta R.; Paraboschi E.M.; Cardamone G.; Duga S.; Gerussi A.; Ciaccio A.; Cristoferi L.; D’Amato D.; Malinverno F.; Mancuso C.; Massironi S.; Milani C.; O’Donnell S.E.; Ronca V.; Barisani D.; Carbone M.; Invernizzi P.; Cordell H.J.; Mells G.F.; Sandford R.N.; Jones D.E.; Nakamura M.; Ueno K.; Tokunaga K.; Hitomi Y.; Kawashima M.; Nishida N.; Kawai Y.; Kohn S.-S.; Nagasaki M.; Gervais O.; Tanaka A.; Takikawa H.; Tang R.; Xiong M.; Li Z.; Shi Y.; Liu X.; Hirschfield G.; Siminovitch K.A.; Gershwin M.E.; Seldin M.F.; Walker E.; Xie G.; Mason A.; Myers R.; Peltekian K.; Ghent C.; Atkinson E.; Juran B.; Lazaridis K.; Lu Y.; Gu X.; Jing K.; Amos C.; Affronti A.; Brunetto M.; Coco B.; Spinzi G.; Elia G.; Ferrari C.; Lleo A.; Muratori L.; Muratori P.; Portincasa P.; Colli A.; Bruno S.; Colloredo G.; Azzaroli F.; Andreone P.; Bragazzi M.; Alvaro D.; Cardinale V.; Cazzagon N.; Rigamonti C.; Floreani A.; Rosina F.; Lampertico P.; Donato F.; Fagiuoli S.; Almasio P.L.; Giannini E.; Cursaro C.; Colombo M.; Valenti L.; Miele L.; Andriulli A.; Niro G.A.; Grattagliano I.; Morini L.; Casella G.; Vinci M.; Battezzati P.M.; Crosignani A.; Zuin M.; Mattalia A.; Calvaruso V.; Colombo S.; Benedetti A.; Marzioni M.; Galli A.; Marra F.; Tarocchi M.; Picciotto A.; Morisco F.; Fabris L.; Croce L.S.; Tiribelli C.; Toniutto P.; Strazzabosco M.; Ch’ng C.L.; Thomas C.; Rahman M.; Yapp T.; Sturgess R.; Harrison M.; Healey C.; Galaska R.; Czajkowski M.; Kendall J.; Whiteman J.; Gunasekera A.; Lawlor C.; Gray C.; Gyawali P.; Premchand P.; Kapur K.; Elliott K.; Marley R.; Foster G.; Watson A.; Dias A.; Subhani J.; Harvey R.; McCorry R.; Ramanaden D.; Gasem J.; Mulvaney-Jones C.; Hobson L.; Evans R.; Mathialahan T.; Shorrock C.; Van Duyvenvoorde G.; Lipscomb G.; Loftus A.; Southern P.; Seward K.; Tibble J.; Gorard D.; Penn R.; Palegwala A.; Maiden J.; Damant R.; Jones S.; Dawwas M.; Alexander G.; Dolwani S.; Cloudsdale R.; Prince M.; Foxton M.; Silvestre V.; Elphick D.; Glenn S.; Mitchison H.; Dungca E.; Gooding I.; Wheatley N.; Karmo M.; Doyle H.; Saksena S.; Kent M.; Mendall M.; Patel M.; Hamilton C.; Braim D.; Ede R.; Austin A.; Paton A.; Sayer J.; Lancaster N.; Hankey L.; Hovell C.; Fisher N.; Carter M.; Desousa P.; Koss K.; Piotrowicz A.; Muscariu F.; Musselwhite J.; Grimley C.; Neal D.; Lim G.; Tan L.; Levi S.; Ala A.; Broad A.; Saeed A.; Wood G.; Flahive K.; Brown J.; Nambela E.; Townshend P.; Ford C.; Holder S.; Wilkinson M.; Gordon H.; Palmer C.; Ramage J.; Ridpath J.; Featherstone J.; Ngatchu T.; Grover B.; Nasseri M.; Shaukat S.; Shidrawi R.; Sadeghian J.; Abouda G.; Ali F.; Rolls S.-A.; Rees I.; Salam I.; Narain M.; Brown A.; Crossey M.; Taylor-Robinson S.; Williams S.; Stansfield G.; MacNicol C.; Grellier L.; Wilkins J.; Banim P.; Das D.; Chilton A.; Raymode P.; Heneghan M.; Lee H.-J.; Curtis H.; Gess M.; Drake I.; Durant E.; Aldersley M.; Davies M.; Jones R.; Bishop R.; McNair A.; Srirajaskanthan R.; Pitcher M.; Tripoli S.; Sen S.; Bird G.; Casey R.; Barnardo A.; Kitchen P.; Cowley C.; Yoong K.; Miller R.; Chirag O.; Sivaramakrishnan N.; MacFaul G.; Jones D.; Shah A.; Wright F.; Evans C.; Saha S.; Pollock K.; Bramley P.; Mukhopadhya A.; Fraser A.; Williams D.; Mills P.; Shallcross C.; Campbell S.; Bathgate A.; Shepherd A.; Dillon J.; Rushbrook S.; Przemioslo R.; Macdonald C.; Metcalf J.; Shmueli U.; Davis A.; Naqvi A.; Lee T.; Ryder S.D.; Collier J.; Klass H.; Kent L.; Ninkovic M.; Cramp M.; Sharer N.; Aspinall R.; Goggin P.; Ghosh D.; Douds A.; Hoeroldt B.; Booth J.; Williams E.; Gunter E.; Dewhurst H.; Hussaini H.; Stableforth W.; Ayres R.; Thorburn D.; Marshall E.; Burroughs A.; Mann S.; Lombard M.; Richardson P.; Patanwala I.; Maltby J.; Brookes M.; Mathew R.; Vyas S.; Singhal S.; Gleeson D.; Misra S.; *Butterworth J.; George K.; Harding T.; Douglass A.; Tregonning J.; Panter S.; Sanghi P.; Shearman J.; Bray G.; Butcher G.; Forton D.; Mclindon J.; Cowan M.; Whatley G.; Mandal A.; Gupta H.; Jain S.; Pereira S.; Prasad G.; Watts G.; Wright M.; Neuberger J.; Gordon F.; Unitt E.; Grant A.; Delahooke T.; Higham A.; Brind A.; Cox M.; Ramakrishnan S.; King A.; Collins C.; Whalley S.; Li A.; Fraser J.; Bell A.; Hughes M.; Wong V.S.; Singhal A.; Gee I.; Ang Y.; Ransford R.; Gotto J.; Millson C.; Bowles J.; Hails J.; Wooldridge H.; Abrahams R.; Gibbins A.; Hogben K.; McKay A.; Foale C.; Brighton J.; Williams B.; Hynes A.; Duggan C.; Wilhelmsen E.; Ncube N.; Houghton K.; Ducker S.; Bird B.; Baxter G.; Keggans J.; Grieve E.; Young K.; Ocker K.; Hines F.; Martin K.; Innes C.; Valliani T.; Fairlamb H.; Thornthwaite S.; Eastick A.; Tanqueray E.; Morrison J.; Holbrook B.; Browning J.; Walker K.; Congreave S.; Verheyden J.; Slininger S.; Stafford L.; O’Donnell D.; Ainsworth M.; Lord S.; March L.; Dickson C.; Simpson D.; Longhurst B.; Hayes M.; Shpuza E.; White N.; Besley S.; Pearson S.; Wright A.; Jones L.; Fouracres A.; Farrington L.; Graves L.; Marriott S.; Leoni M.; Tyrer D.; Dalikemmery L.; Lambourne V.; Green M.; Sirdefield D.; Amor K.; Orpe J.; Colley J.; Shinder B.; Jones J.; Mills M.; Carnahan M.; Taylor N.; Boulton K.; Brown C.; Clifford G.; Archer E.; Hamilton M.; Curtis J.; Shewan T.; Walsh S.; Warner K.; Netherton K.; Mupudzi M.; Gunson B.; Gitahi J.; Gocher D.; Batham S.; Pateman H.; Desmennu S.; Conder J.; Clement D.; Gallagher S.; Chan P.; Currie L.; O’Donohoe L.; Oblak M.; Morgan L.; Quinn M.; Amey I.; Baird Y.; Cotterill D.; Cumlat L.; Winter L.; Greer S.; Spurdle K.; Allison J.; Dyer S.; Sweeting H.; Kordula J.; Aiba Y.; Nakamura H.; Abiru S.; Nagaoka S.; Komori A.; Yatsuhashi H.; Ishibashi H.; Ito M.; Migita K.; Ohira H.; Katsushima S.; Naganuma A.; Sugi K.; Komatsu T.; Mannami T.; Matsushita K.; Yoshizawa K.; Makita F.; Nikami T.; Nishimura H.; Kouno H.; Ota H.; Komura T.; Nakamura Y.; Shimada M.; Hirashima N.; Komeda T.; Ario K.; Nakamuta M.; Yamashita T.; Furuta K.; Kikuchi M.; Naeshiro N.; Takahashi H.; Mano Y.; Tsunematsu S.; Yabuuchi I.; Shimada Y.; Yamauchi K.; Sugimoto R.; Sakai H.; Mita E.; Koda M.; Tsuruta S.; Kamitsukasa H.; Sato T.; Masaki N.; Kobata T.; Fukushima N.; Higuchi N.; Ohara Y.; Muro T.; Takesaki E.; Takaki H.; Yamamoto T.; Kato M.; Nagaoki Y.; Hayashi S.; Ishida J.; Watanabe Y.; Kobayashi M.; Koga M.; Saoshiro T.; Yagura M.; Hirata K.; Zeniya M.; Abe M.; Onji M.; Kaneko S.; Honda M.; Arai K.; Arinaga-Hino T.; Hashimoto E.; Taniai M.; Umemura T.; Joshita S.; Nakao K.; Ichikawa T.; Shibata H.; Yamagiwa S.; Seike M.; Honda K.; Sakisaka S.; Takeyama Y.; Harada M.; Senju M.; Yokosuka O.; Kanda T.; Ueno Y.; Kikuchi K.; Ebinuma H.; Himoto T.; Yasunami M.; Murata K.; Mizokami M.; Shimoda S.; Miyake Y.; Takaki A.; Yamamoto K.; Hirano K.; Ichida T.; Ido A.; Tsubouchi H.; Chayama K.; Harada K.; Nakanuma Y.; Maehara Y.; Taketomi A.; Shirabe K.; Soejima Y.; Mori A.; Yagi S.; Uemoto S.; Tanaka T.; Yamashiki N.; Tamura S.; Sugawara Y.; Kokudo N.

Citation:
Gastroenterology; Jun 2021; vol. 160 (no. 7); p. 2483

Abstract:
Background & Aims: Genome-wide association studies in primary biliary cholangitis (PBC) have failed to find X chromosome (chrX) variants associated with the disease. Here, we specifically explore the chrX contribution to PBC, a sexually dimorphic complex autoimmune disease. Method(s): We performed a chrX-wide association study, including genotype data from 5 genome-wide association studies (from Italy, United Kingdom, Canada, China, and Japan; 5244 case patients and 11,875 control individuals). Result(s): Single-marker association analyses found approximately 100 loci displaying P < 5 x 10-4, with the most significant being a signal within the OTUD5 gene (rs3027490; P = 4.80 x 10-6; odds ratio [OR], 1.39; 95% confidence interval [CI], 1.028-1.88; Japanese cohort). Although the transethnic meta-analysis evidenced only a suggestive signal (rs2239452, mapping within the PIM2 gene; OR, 1.17; 95% CI, 1.09-1.26; P = 9.93 x 10-8), the population-specific meta-analysis showed a genome-wide significant locus in East Asian individuals pointing to the same region (rs7059064, mapping within the GRIPAP1 gene; P = 6.2 x 10-9; OR, 1.33; 95% CI, 1.21-1.46). Indeed, rs7059064 tags a unique linkage disequilibrium block including 7 genes: TIMM17B, PQBP1, PIM2, SLC35A2, OTUD5, KCND1, and GRIPAP1, as well as a superenhancer (GH0XJ048933 within OTUD5) targeting all these genes. GH0XJ048933 is also predicted to target FOXP3, the main T-regulatory cell lineage specification factor. Consistently, OTUD5 and FOXP3 RNA levels were up-regulated in PBC case patients (1.75- and 1.64-fold, respectively). Conclusion(s): This work represents the first comprehensive study, to our knowledge, of the chrX contribution to the genetics of an autoimmune liver disease and shows a novel PBC-related genome-wide significant locus.

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Randomised controlled trial of antibiotic/ hydroxychloroquine combination versus standard budesonide in active Crohn’s disease (Apricot) (2021)

Type of publication:
Conference abstract

Author(s):
Rhodes J.; Subramanian S.; Martin K.; Probert C.; Flanagan P.; Horgan G.; Mansfield J.; Parkes M.; Hart A.; Dallal H.; Iqbal T.; *Butterworth J.; Culshaw K.

Citation:
Gut; Jan 2021; vol. 70

Abstract:
Introduction Mucosal E. coli are increased in Crohn’s disease (CD). They replicate within macrophages and are then inaccessible to penicillins and gentamicin. Hydroxychloroquine is used with doxycycline to treat Whipple’s disease. It raises macrophage intra-vesicular pH and inhibits replication of bacteria that require acidic pH. Ciprofloxacin and doxycycline are also effective against E. coli within macrophages. Methods Adult patients with active CD (CDAI>220 plus CRP>=5 mg/l and/or faecal calprotectin >250 ugram/g) were randomised to receive (open label) either oral budesonide (Entocort CR 9 mg/day 8 weeks, then 6 mg/day 2 weeks and 3 mg/day 2 weeks) or antibiotics/hydroxychloroquine (AB/ HCQ) – oral ciprofloxacin 500 mg bd, doxycycline 100 mg bd, hydroxychloroquine 200 mgs tds for 4 weeks, followed by doxycycline 100 mg bd and hydroxychloroquine 200 mgs tds for 20 weeks. Use of anti-TNF in the previous 3 months was an exclusion. Primary endpoints were remission (CDAI

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Anti-SARS-CoV-2 antibody responses are attenuated in patients with IBD treated with infliximab (2021)

Type of publication:
Journal article

Author(s):
Kennedy N.A.; Goodhand J.R.; Chee D.; Lin S.; Chanchlani N.; Ahmad T.; Bewshea C.; Nice R.; McDonald T.J.; *Butterworth J.; Cooney R.; Croft N.M.; Kok K.B.; Hart A.L.; Irving P.M.; Lamb C.A.; Limdi J.K.; Macdonald J.; McGovern D.P.; Mehta S.J.; Murray C.D.; Patel K.V.; Pollok R.C.; Raine T.; Russell R.K.; Selinger C.P.; Smith P.J.; Bowden J.; Lees C.W.; Sebastian S.; Powell N.

Collaborators at Shrewsbury and Telford Hospital NHS Trust: *Jeff Butterworth, *Colene Adams, *Elizabeth Buckingham, *Danielle Childs, *Alison Magness, *Jo Stickley.

Citation:
Gut; May 2021; vol. 70 (no. 5); p. 865-875

Abstract:
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 alpha4beta7 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. RESULT(S): 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). CONCLUSION(S): 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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Impact of gastrografin in clinical practice in the management of small bowel obstruction of various etiologies (2020)

Type of publication:
Conference abstract

Author(s):
*Karim M.O.; *Jamshed M.H.

Citation:
British Journal of Surgery; Jun 2020; vol. 107 ; p. 204

Abstract:
Aim: Gastrografin has shown to accelerate the resolution of small bowel obstruction of certain etiologies. This audit aims to review the outcome of oral gastrografin (OG) in patients with the small bowel obstruction of diverse causes diagnosed on radiological investigation.
Method(s): A retrospective study of 57 patients who had oral gastrograffin for small bowel obstruction
between 1st June 2018 to 30th June 2019 was included in this study.
Result(s): After excluding 9 patients, 48 included in the study who met the inclusion criterion. 31 patients had adhesive small bowel obstruction (ASBO), of these symptoms resolved in 52% after OG, all patients with postoperative ileus (9), Crohn’s stricture (3) and constipation with small bowel dilatation (1) showed resolution of obstructive symptoms with oral gastrografin. 2 patients out of 3 with serosal/peritoneal metastasis showed response to oral gastrografin.
Conclusion(s): Gastrografin is beneficial and safe to use as a therapeutic agent in a carefully selected patient with certain GI conditions including adhesive small bowel obstruction, postoperative ileus, Crohn’s stricture, constipation, serosal metastasis (peritoneal cancer). Appropriate use of gastrografin can reduce the need for surgical intervention and hospital stay.

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Development of internal validation of clinical prediction models for outcomes of complicated intra-abdominal infection (2021)

Type of publication:
Journal article

Author(s):
Ahmed, S; Bonnett, L; Melhuish, A; Adil, M T; Aggarwal, I; Ali, W; Bennett, J; Boldock, E; Burns, F A; Czarniak, E; Dennis, R; Flower, B; Fok, R; Goodman, A; Halai, S; Hanna, T; Hashem, M; Hodgson, S H; Hughes, G; Hurndalm, K-H; Hyland, R; Iqbal, M R; Jarchow-MacDonald, A; Kailavasan, M; Klimovskij, M; Laliotis, A; Lambourne, J; Lawday, S; Lee, F; Lindsey, B; Lund, J N; Mabayoje, D A; Malik, K I; Muir, A; Narula, H S; Ofor, U; Parsons, H; *Pavelle, T; Prescott, K; Rajgopal, A; Roy, I; Sagar, J; Scarborough, C; Shaikh, S; Smart, C J; Snape, S; Tabaqchali, M; Tennakoon, A; Tilley, R; Vink, E; White, L; Burke, D; Kirby, A

Citation:
The British Journal of Surgery; Apr 30;108(4):441-447

Abstract:
BACKGROUND Complicated intra-abdominal infections (cIAIs) are associated with significant morbidity and mortality. The aim of this study was to describe the clinical characteristics of patients with cIAI in a multicentre study and to develop clinical prediction models (CPMs) to help identify patients at risk of mortality or relapse.METHODS A multicentre observational study was conducted from August 2016 to February 2017 in the UK. Adult patients diagnosed with cIAI were included. Multivariable logistic regression was performed to develop CPMs for mortality and cIAI relapse. The c-statistic was used to test model discrimination. Model calibration was tested using calibration slopes and calibration in the large (CITL). The CPMs were then presented as point scoring systems and validated further.RESULTS Overall, 417 patients from 31 surgical centres were included in the analysis. At 90 days after diagnosis, 17.3 per cent had a cIAI relapse and the mortality rate was 11.3 per cent. Predictors in the mortality model were age, cIAI aetiology, presence of a perforated viscus and source control procedure. Predictors of cIAI relapse included the presence of collections, outcome of initial management, and duration of antibiotic treatment. The c-statistic adjusted for model optimism was 0.79 (95 per cent c.i. 0.75 to 0.87) and 0.74 (0.73 to 0.85) for mortality and cIAI relapse CPMs. Adjusted calibration slopes were 0.88 (95 per cent c.i. 0.76 to 0.90) for the mortality model and 0.91 (0.88 to 0.94) for the relapse model; CITL was -0.19 (95 per cent c.i. -0.39 to -0.12) and – 0.01 (- 0.17 to -0.03) respectively.CONCLUSION Relapse of infection and death after complicated intra-abdominal infections are common. Clinical prediction models were developed to identify patients at increased risk of relapse or death after treatment, although these require external validation.

Improving survivorship: A novel partnership between a large colorectal unit and the charity Bowel Cancer UK (2020)

Type of publication:
Conference abstract

Author(s):
*Hamilton E.; *Lloyd A.; *Cheetham M.; Wix S.; Stone R.

Citation:
Colorectal Disease; Jul 2020; vol. 22 ; p. 54

Abstract:
Background: Bowel Cancer UK and the NHS both have a focus on developing personalised care packages for patients with bowel cancer. Optimising digital information available and signposting patients to resources or events, both locally and nationally can help living well, with and beyond cancer . Method(s): A partnership was initiated between a large district general hospital and Bowel Cancer UK, to refer patients to the charity during clinical appointments, aided by leaflets and information provided on clinical letters. ‘Active signposting’ commenced September 2019 and will run until April 2020. A cohort of patients has completed a survey to identify uptake, aiding planning of future services. Result(s): 136 new patients were signposted to the charity to date. 70% of patients identified that they had been given information about the website from the hospital, but only 29% subsequently visited the website. 40% of patients stated that a referral letter from the hospital would make them more likely to use the website; patients did not request or identify any other new services that they would find useful. The next phase will involve signposting patients three months after diagnosis. Conclusion(s): This partnership will form part of the personalised care package for patients and is a model that other trusts could consider. Feedback received will help shape future resources and events made available to patients, and help develop a template for NHS Trusts working in partnership with Bowel Cancer UK.

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The correlation between bowel complications and cardiac surgery (2020)

Type of publication:
Journal article

Author(s):
Mishra V.; Hewage S.; *Islam S.; Harky A.

Citation:
Scandinavian Journal of Surgery; Dec 2020

Abstract:
Although advances in knowledge and technology have improved outcomes in surgical cardiac patients over the last decade, complications following cardiac operations still remain to be potentially fatal. Gastrointestinal complications, in particular, tend to have high rates of reintervention and mortality following cardiac surgery, with ischemia and hemorrhage being two of the commonest underlying causes. The intention of this review is to identify which risk factors play important roles in predisposing patients to such complications and to gain better insight into the pathogenesis of the sequelae. Furthermore, strategies for prevention have been discussed to educate and increase awareness of how adverse cardiac surgical outcomes can be minimized.

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A Complex Case of Adalimumab Induced Pleuropericarditis in a Patient with Underlying Ulcerative Colitis (2021)

Type of publication:
Journal article

Author(s):
*Abbasi A, *Day S, Subahani M, *Townson G

Citation:
Asploro Journal of Biomedical and Clinical Case Reports, 2021 Jan; 4(1) p.16-21

Abstract:
Introduction: Adalimumab is an anti-tumour necrosis factor (anti-TNF) monoclonal antibody and an important part of the treatment regime for autoimmune conditions including inflammatory bowel disease. We present a case of adalimumab induced pleuropericarditis and discuss the diagnosis challenges we faced.
Case History: A 22-year-old male presented to the emergency department with 3 days history of headache, malaise, fever and right-sided chest pain. He was diagnosed with ulcerative colitis 8 months ago but failed to respond to mesalazine, requiring high dose steroids to induce disease remission. His mesalazine was stopped after 4 months and he was initiated on adalimumab 2 months prior to the current presentation. At presentation, he had a temperature of 38.7 °C (101.6 °F) but no other physical signs. His inflammatory markers were raised, and the chest x-ray was clear. He was started on empirical intravenous antibiotics on suspicion of the underlying infective process. On day 4 the patient developed a new pleural rub and crepitations on both lung bases. An urgent echocardiogram and computed tomography scan of the thorax abdomen and pelvis revealed pleural effusion and a 1.8 cm diameter pericardial effusion. Extensive investigation including virology screen, autoimmune screen and pleural fluid analysis were normal.
Diagnosis, Management and Outcome: This case was discussed in a multidisciplinary meeting. A diagnosis of pleuropericarditis secondary to adalimumab was made. Adalimumab and antibiotics were stopped, and he was started on a course of oral steroids. The patient responded well to the treatment and his symptoms resolved.
Conclusion: Rare drug toxicity should be part of differential diagnosis, especially in young patients with unusual presentation. An early multidisciplinary approach is crucial for a positive outcome. The patient should be actively involved in decision making to improve long term outcome.

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Can adjuncts to bowel preparation for colonoscopy improve patient experience and result in superior bowel cleanliness? A systematic review and meta-analysis (2020)

Type of publication:
Systematic Review

Author(s):
Kamran, Umair; *Abbasi, Abdullah; Tahir, Imran; Hodson, James; Siau, Keith

Citation:
United European gastroenterology journal; Aug 2020 [epub ahead of print]

Abstract:
BACKGROUND Bowel preparation for colonoscopy is often poorly tolerated due to poor palatability and adverse effects. This can negatively impact on the patient experience and on the quality of bowel preparation. This systematic review and meta-analysis was carried out to assess whether adjuncts to bowel preparation affected palatability, tolerability and quality of bowel preparation (bowel cleanliness).METHODS A systematic search strategy was conducted on PubMed, MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews to identify studies evaluating adjunct use for colonoscopic bowel preparation. Studies comparing different regimens and volumes were excluded. Specific outcomes studied included palatability (taste), willingness to repeat bowel preparation, gastrointestinal adverse events and the quality of bowel preparation. Data across studies were pooled using a random-effects model and heterogeneity assessed using I2-statistics.RESULTS Of 467 studies screened, six were included for analysis (all single-blind randomised trials; n = 1187 patients). Adjuncts comprised citrus reticulata peel, orange juice, menthol candy drops, simethicone, Coke Zero and sugar-free chewing gum. Overall, adjunct use was associated with improved palatability (mean difference 0.62, 95% confidence interval 0.29-0.96, p < 0.001) on a scale of 0-5, acceptability of taste (odds ratio 2.75, 95% confidence interval: 1.52-4.95, p < 0.001) and willingness to repeat bowel preparation (odds ratio 2.92, 95% confidence interval: 1.97-4.35, p < 0.001). Patients in the adjunct group reported lower rates of bloating (odds ratio 0.48, 95% confidence interval: 0.29-0.77, p = 0.003) and vomiting (odds ratio 0.47, 95% confidence interval 0.27-0.81, p = 0.007), but no difference in nausea (p = 0.10) or abdominal pain (p = 0.62). Adjunct use resulted in superior bowel cleanliness (odds ratio 2.52, 95% confidence interval: 1.31-4.85, p = 0.006). Heterogeneity varied across outcomes, ranging from 0% (vomiting) to 81% (palatability), without evidence of publication bias. The overall quality of evidence was rated moderate.CONCLUSION In this meta-analysis, the use of adjuncts was associated with better palatability, less vomiting and bloating, willingness to repeat bowel preparation and superior quality of bowel preparation. The addition of adjuncts to bowel preparation may improve outcomes of colonoscopy and the overall patient experience.

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Randomized Trial of Ciprofloxacin Doxycycline and Hydroxychloroquine Versus Budesonide in Active Crohn’s Disease (2021)

Type of publication:
Randomised controlled trial

Author(s):
Rhodes J.M.; Subramanian S.; Martin K.; Probert C.; Flanagan P.K.; Horgan G.W.; Mansfield J.; Parkes M.; Hart A.; Dallal H.; Iqbal T.; *Butterworth J.; Culshaw K.

Citation:
Digestive Diseases and Sciences; Aug 2021; vol. 66 (no. 8); p. 2700-2711

Abstract:
Background: Increased mucosa-associated E. coli are present in Crohn’s disease, but their role in pathogenesis is uncertain. Aim(s): To assess efficacy and safety of an antibiotic/hydroxychloroquine combination effective against E. coli inside macrophages. Method(s): Adults with moderately active disease (CDAI > 220-450 plus C reactive protein >= 5 mg/l and/or fecal calprotectin > 250 mug/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. Result(s): 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(s): 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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