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 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; Feb 2021 [epub ahead of print]

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.

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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 (2020)

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; 2020 [epub ahead of print]

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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Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial (2020)

Type of publication:
Randomised controlled trial

Author(s):
The HALT-IT Trial Collaborators (including *John Jones and *Charlotte Owen)

Citation:
Lancet, 2020; Vol. 395: pp. 1927–36

Abstract:
Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding.
Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124.
Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid
(5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11952 (99·5%) received the first dose of the allocated
treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the
tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18).
Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and
placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein
thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of
5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98).
Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our
results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a
randomised trial.

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Duplication of the Gallbladder and its Surgical Challenges (2019)

Type of publication:
Conference abstract

Author(s):
*Tamvakeras P.; *Riera M.

Citation:
British Journal of Surgery; Sep 2019; vol. 106, S6; p. 28

Abstract:
Aims: Duplication of the gallbladder is a rare congenital anomaly. However, awareness of this anatomical variation is crucial when treating gallstone disease. We present the case of a patient with two gallbladders, incidentally found during laparoscopic cholecystectomy. We review the literature and discuss the associated surgical challenges.
Methods: Case presentation and literature review of the classification, clinical presentation, radiological diagnosis and management of gallbladder duplication.
Results: A 37 year old healthy man presented with a two year history of post prandial right upper quadrant abdominal pain. Routine blood investigations were normal and ultrasonography (US) demonstrated gallstones with normal biliary ducts. During laparoscopy he was found to have gallbladder duplication with a Y-shaped type cystic duct, this consisted of two ducts joining together to form a main cystic duct which drained into an otherwise normal common bile duct. No cholangiogram was performed. After meticulous dissection and demonstration of the anatomy, the cholecystectomy was performed. The patient recovered uneventfully and was discharged the next day. Histology showed gallstones and chronic inflammation in both
gallbladders.
Conclusions: A duplicate gallbladder is a rare congenital variation. Preoperative diagnosis can be challenging. Understanding its classification based on the relational anatomy to the biliary tree is essential to avoid biliary injuries. Imaging modalities such as US and computed tomography (CT) may not be sensitive enough. MRCP may demonstrate the biliary tree more clearly. Laparoscopic cholecystectomy can be safely performed, in the presence of symptomatic gallstone disease.

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