Stepped-wedge randomized controlled trial of laparoscopic ventral mesh rectopexy in adults with chronic constipation (2022)

Type of publication:Journal article

Author(s):Grossi U; *Lacy-Colson J; Brown SR; Cross S; Eldridge S; Jordan M; Mason J; Norton C; Scott SM; Stevens N; Taheri S; Knowles CH

Citation:Techniques in Coloproctology, 2022 May 19 [epub ahead of print]

Abstract:Background: The effectiveness of laparoscopic ventral mesh rectopexy (LVMR) in patients with defecatory disorders secondary to internal rectal prolapse is poorly evidenced. A UK-based multicenter randomized controlled trial was designed to determine the clinical efficacy of LVMR compared to controls at medium-term follow-up. Methods: The randomized controlled trial was conducted from March 1, 2015 TO January 31, 2019. A stepped-wedge RCT design permitted observer-masked data comparisons between patients awaiting LVMR (controls) with those who had undergone surgery. Adult participants with radiologically confirmed IRP refractory to conservative treatment were randomized to three arms with different delays before surgery. Efficacy outcome data were collected at equally stepped time points (12, 24, 36, 48, 60, and 72 weeks). Clinical efficacy of LVMR compared to controls was defined as ≥ 1.0-point reduction in Patient Assessment of Constipation-Quality of Life and/or Symptoms (PAC-QOL and/or PAC-SYM) scores at 24 weeks. Secondary outcome measures included 14-day diary data, the Generalized Anxiety Disorder scale (GAD-7), the Patient Health Questionnaire-9 (PHQ-9), St Marks incontinence score, the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12), the chronic constipation Behavioral Response to Illness Questionnaire (CC-BRQ), and the Brief Illness Perception Questionnaire (BIPQ).Results: Of a calculated sample size of 114, only 28 patients (100% female) were randomized from 6 institutions (due mainly to national pause on mesh-related surgery). Nine were assigned to the T0 arm, 10 to T12, and 9 to T24. There were no substantial differences in baseline characteristics between the three arms. Compared to baseline, significant reduction (improvement) in PAC-QOL and PAC-SYM scores were observed at 24 weeks post-surgery (- 1.09 [95% CI – 1.76, – 0.41], p = 0.0019, and – 0.92 [- 1.52, – 0.32], p = 0.0029, respectively) in the 19 patients available for analysis (9 were excluded for dropout [n = 2] or missing primary outcome [n = 7]). There was a clinically significant long-term reduction in PAC-QOL scores (- 1.38 [- 2.94, 0.19], p = 0.0840 at 72 weeks). Statistically significant improvements in PAC-SYM scores persisted to 72 weeks (- 1.51 [- 2.87, – 0.16], p = 0.0289). Compared to baseline, no differences were found in secondary outcomes, except for significant improvements at 24 and 48 weeks on CC-BRQ avoidance behavior (- 14.3 [95% CI – 23.3, – 5.4], and – 0.92 [- 1.52, – 0.32], respectively), CC-BRQ safety behavior (- 13.7 [95% CI – 20.5, – 7.0], and – 13.0 [- 19.8, – 6.1], respectively), and BIPQ negative perceptions (- 16.3 [95% CI – 23.5, – 9.0], and – 10.5 [- 17.9, – 3.2], respectively).Conclusions: With the caveat of under-powering due to poor recruitment, the study presents the first randomized trial evidence of short-term benefit of LVMR for internal rectal prolapse. Trial Registration: ISRCTN Registry (ISRCTN11747152)

Validation of the OAKS prognostic model for acute kidney injury after gastrointestinal surgery (2022)

Type of publication:Journal article

Author(s):STARSurg Collaborative and EuroSurg Collaborative (includes Chohan K.; Dhuna S.; Haq T.; Kirby S.; Lacy-Colson J.; Logan P.; Malik Q.; McCann J.; Mughal Z.; Sadiq S.; Sharif I.; Shingles C.; Simon A.; Chaudhury N.; Rajendran K.; Akbar Z.)

Citation:BJS Open, 2022, 6(1)

Abstract:Background: Postoperative acute kidney injury (AKI) is a common complication of major gastrointestinal surgery with an impact on short- and long-term survival. No validated system for risk stratification exists for this patient group. This study aimed to validate externally a prognostic model for AKI after major gastrointestinal surgery in two multicentre cohort studies. Method(s): The Outcomes After Kidney injury in Surgery (OAKS) prognostic model was developed to predict risk of AKI in the 7 days after surgery using six routine datapoints (age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker). Validation was performed within two independent cohorts: a prospective multicentre, international study ('IMAGINE') of patients undergoing elective colorectal surgery (2018); and a retrospective regional cohort study ('Tayside') in major abdominal surgery (2011-2015). Multivariable logistic regression was used to predict risk of AKI, with multiple imputation used to account for data missing at random. Prognostic accuracy was assessed for patients at high risk (greater than 20 per cent) of postoperative AKI. Result(s): In the validation cohorts, 12.9 per cent of patients (661 of 5106) in IMAGINE and 14.7 per cent (106 of 719 patients) in Tayside developed 7-day postoperative AKI. Using the OAKS model, 558 patients (9.6 per cent) were classified as high risk. Less than 10 per cent of patients classified as low-risk developed AKI in either cohort (negative predictive value greater than 0.9). Upon external validation, the OAKS model retained an area under the receiver operating characteristic (AUC) curve of range 0.655-0.681 (Tayside 95 per cent c.i. 0.596 to 0.714; IMAGINE 95 per cent c.i. 0.659 to 0.703), sensitivity values range 0.323-0.352 (IMAGINE 95 per cent c.i. 0.281 to 0.368; Tayside 95 per cent c.i. 0.253 to 0.461), and specificity range 0.881-0.890 (Tayside 95 per cent c.i. 0.853 to 0.905; IMAGINE 95 per cent c.i. 0.881 to 0.899). Conclusion(s): The OAKS prognostic model can identify patients who are not at high risk of postoperative AKI after gastrointestinal surgery with high specificity.

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A single faecal bile acid stool test demonstrates potential efficacy in replacing SeHCAT testing for bile acid diarrhoea in selected patients (2022)

Type of publication:Journal article

Author(s):Kumar A; Al-Hassi HO; Jain M; Phipps O; Ford C; Gama R; Steed H; *Butterworth J; McLaughlin J; Galbraith N; Brookes MJ; Hughes LE

Citation:Scientific Reports, 2022 May 18; Vol. 12 (1), pp. 8313

Abstract:This study examines the validity of measuring faecal bile acids (FBA) in a single stool sample as a diagnostic tool for bile acid diarrhoea (BAD) by direct comparison to the 75 selenium-homotaurocholic acid (SeHCAT) scan. A prospective observational study was undertaken. Patients with chronic diarrhoea (> 6 weeks) being investigated for potential BAD with SeHCAT scan provided stool samples for measurement of FBA, using an enzyme-linked immunosorbent assay. Patients were characterised into four groups: SeHCAT negative control group, post-cholecystectomy, idiopathic BAD and post-operative terminal ileal resected Crohn's disease. Stool samples were collected at baseline and 8-weeks post treatment to determine whether FBA measurement could be used to monitor therapeutic response. 113 patients had a stool sample to directly compare with their SeHCAT result. FBA concentrations (μmol/g) and interquartile ranges in patients in the control group (2.8; 1.6-4.2), BAD (3.6; 1.9-7.2) and post-cholecystectomy cohort 3.8 (2.3-6.8) were similar, but all were significantly lower (p < 0.001) compared to the Crohn's disease cohort (11.8; 10.1-16.2). FBA concentrations in patients with SeHCAT retention of < 15% (4.95; 2.6-10.5) and < 5% (9.9; 4.8-15.4) were significantly higher than those with a SeHCAT retention > 15% (2.6; 1.6-4.2); (p < 0.001 and p < 0.0001, respectively). The sensitivity and specificity using FBA cut-off of 1.6 μmol/g (using ≤ 15% SeHCAT retention as diagnostic of BAD) were 90% and 25% respectively. A single random stool sample may have potential use in diagnosing severe BAD or BAD in Crohn's patients. Larger studies are now needed to confirm the potential efficacy of this test to accurately diagnose BAD in the absence of SeHCAT testing.

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Are we doing enough to prevent colectomy in inflammatory bowel disease (IBD) patients? A 5-year review of colectomy rates in Shropshire and Mid-Wales UK (2015-2019) (2022)

Type of publication:Conference abstract

Author(s):*Javed A.; *Butterworth J.; *Townson G.

Citation:Journal of Crohn's and Colitis; Jan 2022; vol. 16

Abstract:Background: Colectomy for IBD significantly impacts the psycho-social aspects & quality of life.Method(s): Electronic records were retrospectively analysed for colectomy rates & parameters of interest.Result(s): 68 patients (Men 37:Women31), median age 30 years had colectomies. Annual colectomy rates remained constant;7 (2015), 20 (2016), 11 (2017) & (2018) each and 19 (2019). 28% had colectomy within 1 year of diagnosis and only 63% received a biologic agent. Over half, (54%)had emergency surgeries & 37% experienced infections, re-laparotomy and ileus (20% each).Conclusion(s): There is an opportunity to risk-stratify patients at diagnosis based on the risk factors (men, younger age, severe/extensive disease) to a top-down therapy & treat to target strategy to reduce colectomy rates. (Table Presented).

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Global Impact of COVID-19 pandemic on Gastric Cancer Treatment: findings from a global cross-sectional multicentre study (GLEOHUG-GC) (2022)

Type of publication:Conference abstract

Author(s):Herrera Kok J.H.; Viswanath Y.K.; Parmar C.; Bangash A.H.; Samaduv E.; Atici S.D.; Cheruvu C.V.; Abouelazayem M.; Yang W.; Galanis M.; Di Maggio F.; Isik A.; *Bandopyadaya S.; Mahawar K.

Citation:European Journal of Surgical Oncology; Feb 2022; vol. 48 (no. 2)

Abstract:Background: Gastric cancer (GC) is the 5th most common malignancy and remains one of the major causes of worldwide cancer-related deaths. COVID-19 pandemic has had a significant impact on the provision of cancer care. This study aims to overview the global standpoint of gastric cancer patients (GCP) during the first year of pandemic (PY1).
Material(s) and Method(s): The Upper Gastrointestinal Surgeons (TUGS), within its Global Level of Harm Project, designed an online cross-sectional survey to assess how GCP's management changed during PY1. The questionnaire included 33 questions about expertise, kind of health system, hospital organization and screening policies, personal protective equipment (PPE), change in patient's characteristics, preoperative, operative and postoperative management of GCP.Result(s): There were 209 answers from 178 centres (50 countries) around the world. Results of the survey showed: most hospitals (88,2%) had restricted areas for the management of COVID-19 patients; 53,6% of participants were redeployed; most frequent COVID-19 screening methods were PCR (78,8%) and chest CTscan (25,6%), and 55,9% thought there was a lack of PPE. Preoperative management: 43,2% decrease in the number of multidisciplinary teams (MDT) meetings; 28,4% increase in the number of cT2 or higher GCP; 34,7% increase in metastatic (M1) GCP; 26,8% increase in GCP receiving definitive palliative treatment; 23,7% increase in the number of frail patients; 50% increase in waiting list time (WLT); and 41,6% faced problems in the provision of oncological treatment. Operative management: 54,5% decrease in elective gastrectomies; 29,1% increase in the number of urgent/semi-urgent gastrectomies; 37% decrease in the number of minimally invasive gastrectomies (MIG); and 18,5% increase in the number of surgeries with palliative intent. Postoperative management: 16,5% increase in the overall complication rate (OCR); 12,6% increase in the number of Clavien-Dindo 3 or higher complications; 8% increase in the leak rate; increase in pulmonary infections (26,8%) and bowel obstruction (2,4%); 44,5% development of postoperative COVID-19 infection; 15,4% increase in 30-days mortality rate; 23,1% mortality due to COVID-19 infection; 17,6% increase in the need for adjuvant treatment. Most patients were postoperatively assessed either through a face to face consultation or a combination of face to face and remote consultation.
Conclusion(s): COVID-19 pandemic has affected GC management by decreased frequency of MDT's, higher clinical-stage migration and fuelled frailty. The pandemic increased WLT, the number of urgent and palliative surgeries, OCR, Clavien-Dindo 3 or higher complications, leak rate, and pulmonary infections. There was a noticeable high rate of postoperative COVID-19 infection and associated mortality. Further multicentric studies are warranted to affirm these findings.

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Onyx embolisation of a small bowel arteriovenous malformation prior to resection (2021)

Type of publication:Conference abstract

Author(s):*Jones G.A.R.; *Hinwood D.; *McCloud J.; McCafferty I.

Citation:Colorectal Disease; Sep 2021; vol. 23 ; p. 126

Abstract:Small bowel arteriovenous malformation (AVM) is uncommon with an incidence of approximately 1:100,000. Nevertheless cases causing severe anaemia may necessitate surgery posing the dilemma for the surgeon at operation of exactly which portion of small bowel to resect. We present a case of a rare mid small bowel AVM definitively managed with highly selective mesenteric angiography and embolisation with Onyx immediately prior to surgical resection. Onyx is an injectable embolic fluid for which the main application is in the treatment of brain AVMs. To the authors' knowledge this is the first reported case of its use in small bowel AVM. Being black in colour Onyx demonstrates the location and extent of the abnormal bowel segment allowing preservation of normal small bowel. Secondly it reduces the blood flow in the abnormal segment reducing bleeding. A 24 year old man was referred with severe recurrent iron deficiency anaemia since childhood having required multiple blood transfusions and iron infusions. His diagnosis of mid small bowel AVM was made by capsule endoscopy showing small bowel varices and confirmed with CT angiography. On the day of the procedure at angiography the SMA was catheterised and selective injections confirmed the mid small bowel AVM. Micro catheters were then used to selectively enter jejunal branches and embolisation was performed with Onyx and micro-coils. The patient was transferred to theatre for laparotomy. Small bowel resection was performed transfixing all pedicles and stapled anastamosis. Four months post-operatively the patient has had no further problems with anaemia.

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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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