Baseline Expression of Immune Gene Modules in Blood is Associated With Primary Response to Anti-TNF Therapy in Crohn's Disease Patients (2024)

Type of publication:
Journal article

Author(s):
Journal of Crohn's and Colitis. 18(3) (pp 431-445), 2024. Date of Publication: 01 Mar 2024

Citation:
Reppell M.; Smaoui N.; Waring J.F.; Pivorunas V.; Guay H.; Lin S.; Chanchlani N.; Bewshea C.; Goodhand J.R.; Kennedy N.A.; Anderson C.A.; Patel V.; Mazhar Z.; Saich R.; Colleypriest B.; Tham T.C.; Iqbal T.H.; Kaushik V.; Murugesan S.; Singhi S.; Weaver S.; Preston C.; Butt A.; Smith M.; Basude D.; Beale A.; Langlands S.; Direkze N.; Parkes M.; Torrente F.; De La Revella Negro J.; MacDonald C.E.; Evans S.M.; Gunasekera A.V.J.; Thakur A.; Elphick D.; Shenoy A.; Nwokolo C.U.; Dhar A.; Cole A.T.; Agrawal A.; Bridger S.; Doherty J.; Cooper S.C.; de Silva S.; Mowat C.; Mayhead P.; Lees C.; Jones G.; Hart J.W.; Gaya D.R.; Russell R.K.; Gervais L.; Dunckley P.; Mahmood T.; Banim P.J.R.; Sonwalkar S.; Ghosh D.; Phillips R.H.; Azaz A.; Sebastian S.; Shenderey R.; Armstrong L.; Bell C.; Hariraj R.; Matthews H.; Jafferbhoy H.; Selinger C.P.; Zamvar V.; De Caestecker J.S.; Willmott A.; Miller R.; Babu P.S.; Tzivinikos C.; Bloom S.L.; Chung-Faye G.; Croft N.M.; Fell J.M.E.; Harbord M.; Hart A.; Hope B.; Irving P.M.; Lindsay J.O.; Mawdsley J.E.; McNair A.; Monahan K.J.; Murray C.D.; Orchard T.; Paul T.; Pollok R.; Shah N.; Bouri S.; Johnson M.W.; Modi A.; Kabiru K.D.; Baburajan B.K.; Bhaduri B.; Fagbemi A.A.; Levison S.; Limdi J.K.; Watts G.; Foley S.; Ramadas A.; MacFaul G.; Mansfield J.; Grellier L.; Morris M.-A.; Tremelling M.; Hawkey C.; Kirkham S.; Charlton C.P.J.; Rodrigues A.; Simmons A.; Lewis S.J.; Snook J.; Tighe M.; Goggin P.M.; De Silva A.N.; Lal S.; Smith M.S.; Panter S.; Cummings F.; Dharmisari S.; Carter M.; Watts D.; Mahmood Z.; McLain B.; Sen S.; Pigott A.J.; Hobday D.; Wesley E.; Johnston R.; Edwards C.; Beckly J.; Vani D.; Ramakrishnan S.; Chaudhary R.; Trudgill N.J.; Cooney R.; Bell A.; Prasad N.; Gordon J.N.; Brookes M.J.; Li A.; Gore S.; Bai B.Y.H.; Ahmad T.;

Abstract:
Background and Aims: Anti-tumour necrosis factor [anti-TNF] therapy is widely used for the treatment of inflammatory bowel disease, yet many patients are primary non-responders, failing to respond to induction therapy. We aimed to identify blood gene expression differences between primary responders and primary non-responders to anti-TNF monoclonal antibodies [infliximab and adalimumab], and to predict response status from blood gene expression and clinical data. Method(s): The Personalised Anti-TNF Therapy in Crohn's Disease [PANTS] study is a UK-wide prospective observational cohort study of anti-TNF therapy outcome in anti-TNF-naive Crohn's disease patients [ClinicalTrials.gov identifier: NCT03088449]. Blood gene expression in 324 unique patients was measured by RNA-sequencing at baseline [week 0], and at weeks 14, 30, and 54 after treatment initiation [total sample size = 814]. Result(s): After adjusting for clinical covariates and estimated blood cell composition, baseline expression of major histocompatibility complex, antigen presentation, myeloid cell enriched receptor, and other innate immune gene modules was significantly higher in anti-TNF responders vs non-responders. Expression changes from baseline to week 14 were generally of consistent direction but greater magnitude [i.e. amplified] in responders, but interferon-related genes were upregulated uniquely in non-responders. Expression differences between responders and non-responders observed at week 14 were maintained at weeks 30 and 54. Prediction of response status from baseline clinical data, cell composition, and module expression was poor. Conclusion(s): Baseline gene module expression was associated with primary response to anti-TNF therapy in PANTS patients. However, these baseline expression differences did not predict response with sufficient sensitivity for clinical use.

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Efficacy of atypical antipsychotics in the treatment of fecal incontinence in children and adolescents: a randomized clinical trial (2024)

Type of publication:
Randomised controlled trial

Author(s):
Zahed, Ghazal; Fatahi, Somaye; Tabatabaee, Leila; Imanzadeh, Negar; *Seraj, Shaikh Sanjid; Wolters, Benjamin Hernandez; Hosseini, Amirhossein

Citation:
BMC Pediatrics. 24(1):7, 2024 Jan 03.

Abstract:
OBJECTIVES: Functional retentive overflow incontinence (retentive FI) is the most common cause of fecal soiling in children. Based on the clinical experiences, the treatment of retentive FI in patients with comorbid psychiatric disorders was accelerated when Risperidone was used as treatment for their psychiatric comorbidities; therefore, this study was conducted to evaluate the effect of risperidone in the treatment of retentive FI in children and adolescents. METHODS: In this double-blind, randomized, placebo-controlled trial, 140 patients aged 4-16 years eligible for the study were randomized into two groups, receiving either 0.25-0.5 mg of Risperidone syrup (n = 70) or maltodextrin syrup (placebo group, n = 70) every 12 h daily for 12 weeks. Sociodemographic data, including age, sex, weight, height, BMI, BMI z-score, and socioeconomic status, was recorded, and the number of nocturnal FI, diurnal FI, and painful defecations was measured. RESULTS: 136 participants (69 on Risperidone and 67 on placebo) were included in the study. Mean age of participants in the intervention and placebo groups were 7.2 +/- 2.4 years and 8.0 +/- 3.1 years, respectively. The mean number of nocturnal FI (Ptrend=0.39) and diurnal FI (Ptrend=0.48) in patients without psychiatric comorbidities, and the number of painful defecations for participants with and without psychiatric comorbidities (P = 0.49, P = 0.47, respectively) were not significantly different between the groups, but a significant effect was observed in diurnal FI after Risperidone treatment in patients with psychiatric comorbidities (P < 0.001). CONCLUSION: Risperidone, when used along with other non-pharmacological interventions, may be helpful in treating FI in pediatric patients with psychiatric comorbidities.

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The Short- and Long-Term Safety and Efficacy Profile of Subtotal Cholecystectomy: A Single-Centre, Long-Term, Follow-Up Study (2023)

Type of publication:
Journal article

Author(s):
*Bodla, Ahmed Salman; *Rashid, Muhammad Umair; *Hassan, Maleeha; *Rehman, Saad; *Kirby, George.

Citation:
Cureus. 15(8):e44334, 2023 Aug. [epub ahead of print]

Abstract:
Background Subtotal cholecystectomy (STC) has been reported as an effective method to remove the gallbladder if the hepatocystic triangle anatomy is unfavourable. However, the evidence regarding its long-term outcomes from the United Kingdom (UK) is lacking. This study aimed to assess its short and long-term outcomes with a minimum of one-year follow-up. Methodology We retrospectively analysed all elective and emergency STCs performed in a single UK NHS Trust between 2014 and 2020. Relevant data were collected using electronic patient records and questionnaire-based, long-term, telephonic follow-up (median follow-up of 3.7 years). Outcomes examined were immediate/short-term complications (biliary injury, bile leak, return-to-theatre) and long-term problems (recurrent symptoms, choledocholithiasis, cholangitis/pancreatitis). Results There were a total of 50 STC cases (58% females) out of 4,341 cholecystectomies performed (1.15%), with the median age, body mass index, and length of stay being 69.5 years, 29 kg/m2 and eight days, respectively. Twenty-eight (56%) were emergency. No patient endured bile duct injury. Seven (14%) patients had postoperative bile leak which was significantly more common when Hartmann's pouch was left open (33% vs. 8%; p = 0.03). No bile duct injury was reported. Most were managed conservatively (endoscopic retrograde cholangiopancreatography + stent: four; radiological drainage: one; no intervention: one). Only one patient required laparoscopic lavage and drainage. The true incidence of developing choledocholithiasis over the long term was 4/50 (8%) in our study. The median interval between STC and the diagnosis of postoperative choledocholithiasis was 15.9 months. All four patients had undergone type 1 STC (where the remnant of Hartmann's pouch was closed with sutures); however, subsequent cross-sectional imaging (magnetic resonance cholangiopancreatography or computed tomography) showed that the gallbladder remnant was visible in only two of these four patients. Conclusions STC is a safe option in difficult situations and prevents bile duct injury. Although the risk of bile leak can be reduced by closing Hartmann's pouch remnant, this may slightly increase the risk of subsequent stone formation. Infrequent occurrence of recurrent gallstone-related symptoms or complications favours its use

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Patients' frailty and co-morbidities do not affect short-term mortality following emergency colorectal cancer surgery (2023)

Type of publication:
Journal article

Author(s):
*Mak, Richard; Deckmann, Nico; Collins, Danielle; Maeda, Yasuko.

Citation:
The Surgeon: Journal of the Royal Colleges of Surgeons of Edinburgh & Ireland. February 2024, 22(1):52-59

Abstract:
AIM: To investigate the effects of frailty and co-morbidities on short and medium-term outcome following emergency colorectal cancer surgery. METHODS: Data of patients who underwent emergency colorectal cancer operations between January 2013 and December 2016 were reviewed retrospectively. Collected data included demographic and operative variables, clinical frailty scale (CFS), Charlson comorbidity index (CCI) and cause of death with minimum 3 years follow-up. RESULTS: Three-hundred and six patients (median age 72, range 18-100 years) underwent emergency colorectal cancer surgery; Some 74 (24.2%) patients had metastatic cancer at the time of emergency surgery, 77 (25.2%) were frail (CFS >=4), while 118 (38.6%) were comorbid (CCI of >=8). Thirty-day mortality was 4.2% (13 patients) and a further 12 patients died within 90 days (8.2%). By 1 year 73 (23.9%) patients had died, and by 3 years 151 (49.3%) patients died. Frailty did not impact 30-day mortality (6.5% vs 3.5%, p = 0.26) but frail patients (CFS >=4) had a higher mortality rate at 90 days (16.9% vs 5.2%, p < 0.05), 1 year (37.7% vs 19.2%, p < 0.05) and 3 years (61.0% vs 45.4%, p < 0.05). Similarly, higher comorbidity (CCI >=8) did not impact 30-day mortality (5.9% vs 3.2%, p = 0.25), but they had a higher mortality rate at 90 days (14.4% vs 4.3%, p < 0.05), 1 year (40.7% vs 13.3%, p < 0.05), and 3 years (76.3% vs 32.4%, p < 0.05). CONCLUSION: Thirty-day mortality after emergency colorectal cancer surgery in frail and comorbid patients are similar to that of the general population.

Should gastric band slippage be managed with laparoscopic unclipping and re-clipping? (2023)

Type of publication:
Conference abstract

Author(s):
*Maharaj G.; *Jain R.; *Riera M.

Citation:
14th Annual Scientific Meeting of British Obesity and Metabolic Surgery Society, BOMSS 2023

Abstract:
INTRODUCTION: Laparoscopic Adjustable Gastric Band (LABG) is a popular bariatric procedure. Gastric band slippage is a recognised complication. Treatment options include band removal or unclip. Subsequent re-clip/reposition of a previously unclipped band may provide further weight loss. This study aims to examine patient outcomes following un-clipping of slipped gastric bands. METHOD(S): Electronic Records of patients who underwent gastric band unclipping during a ten year period were examined. RESULT(S): 11 female patients underwent gastric band unclipping, five as emergencies. Nine patients (82%) had confirmed band slippage/pouch dilatation. Mean age at unclip was 46.5yrs. Median duration band insertion to unclip was 7yrs (range 3-11yrs). 8 patients underwent subsequent band reclip/reposition. 1 patient had attempted re-clip converted to removal. Median duration unclip to re-clip was 9months (range 4-14months). 3/8 patients with re-clipped bands had no further procedures and maintained weight loss. Of the remaining five patients, two had early removal because of acute dysphagia on days-2 and 5 post re-clipping. The other three patients eventually suffered further slippage and band intolerance. Median duration re-clip to band removal 2yrs (range 0-4yrs). Two patients were never re-clipped (one had symptomatic removal, the other is awaiting a further procedure). In total, seven bands were removed (64%). Four of these patients suffered significant weight regain, with two requiring revisional surgery. CONCLUSION(S): This study is small. However 64% of patients who underwent gastric band unclipping had subsequent removal. Hence gastric band unclipping does not appear to provide added benefit to patient care, and exposes them to additional procedures.

A Case of the Cascade Stomach; Laparoscopic Sleeve of Fundoplication (2023)

Type of publication:Conference abstract

Author(s):*Davies S.; *Maharaja G.; *Riera M.

Citation:14th Annual Scientific Meeting of British Obesity and Metabolic Surgery Society, BOMSS 2023

Abstract:A Case of the Cascade Stomach; Sleeve of Fundoplication Introduction The cascade stomach is a long standing known entity often referred to as 'cup and spill deformity' but very little is known on the management of these cases particularly surgically. Cases often present with acid reflux and vomiting due to the physiological and anatomical deformity of the stomach and are subsequently referred to the benign upper gastrointestinal/bariatric surgeon to manage. Surgical options reported in the literature are sparse but include gastropexy, laparoscopic sleeve gastrectomy and laparoscopic fundoplication. Methods We present this unusual condition as a case report, discuss the challenges in management and propose surgical management options. Conclusion Although rare this cases propose a challenge to the benign UGI surgeon as currently there is very little in the literature to support best management options. This unusual case was managed with a laparoscopic Nissen's fundoplication and we further propose that this should potentially be the standard recognised course of treatment in these cases due to the pathophysiological nature of this condition and the functional process which often leads to these patients to be high risk of acid reflux.

Habit training versus habit training with direct visual biofeedback in adults with chronic constipation: A randomized controlled trial (2023)

Type of publication:
Journal article

Author(s):
Norton, Christine; Bannister, Sybil; Booth, Lesley; Brown, Steve R; Cross, Samantha; Eldridge, Sandra; Emmett, Christopher; Grossi, Ugo; Jordan, Mary; *Lacy-Colson, Jon; Mason, James; McLaughlin, John; Moss-Morris, Rona; Scott, S Mark; Stevens, Natasha; Taheri, Shiva; Taylor, Stuart A; Yiannakou, Yan; Knowles, Charles H.

Citation:
Colorectal Disease. 25(11):2243-2256, 2023 Nov.

Abstract:
AIM: The aim was to determine whether specialist-led habit training using Habit Training with Biofeedback (HTBF) is more effective than specialist-led habit training alone (HT) for chronic constipation and whether outcomes of interventions are improved by stratification to HTBF or HT based on diagnosis (functional defaecation disorder vs. no functional defaecation disorder) by radio-physiological investigations (INVEST). METHOD: This was a parallel three-arm randomized single-blinded controlled trial, permitting two randomized comparisons: HTBF versus HT alone; INVEST- versus no-INVEST-guided intervention. The inclusion criteria were age 18-70 years; attending specialist hospitals in England; self-reported constipation for >6 months; refractory to basic treatment. The main exclusions were secondary constipation and previous experience of the trial interventions. The primary outcome was the mean change in Patient Assessment of Constipation Quality of Life score at 6 months on intention to treat. The secondary outcomes were validated disease-specific and psychological questionnaires and cost-effectiveness (based on EQ-5D-5L). RESULTS: In all, 182 patients were randomized 3:3:2 (target 384): HT n = 68; HTBF n = 68; INVEST-guided treatment n = 46. All interventions had similar reductions (improvement) in the primary outcome at 6 months (approximately -0.8 points of a 4-point scale) with no statistically significant difference between HT and HTBF (-0.03 points; 95% CI -0.33 to 0.27; P = 0.85) or INVEST versus no-INVEST (0.22; -0.11 to 0.55; P = 0.19). Secondary outcomes showed a benefit for all interventions with no evidence of greater cost-effectiveness of HTBF or INVEST compared with HT. CONCLUSION: The results of the study at 6 months were inconclusive. However, with the caveat of under-recruitment and further attrition at 6 months, a simple, cheaper approach to intervention may be as clinically effective and more cost-effective than more complex and invasive approaches.

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Identifying Cases Of Pernicious Anaemia For Offering Baseline/Surveillance Gastroscopies as per BSG Guidance - Service Development In Shropshire (2023)

Type of publication:
Conference abstract

Author(s):
*Rafique H.; *Rugemintwaza J.; *Mostafa W.; *Smith M.;

Citation:
Gut. Conference: Annual Meeting of the British Society of Gastroenterology, BSG 2023. Liverpool United Kingdom. 72(Supplement 2) (pp A178-A179), 2023. Date of Publication: June 2023.

Abstract:
Introduction Pernicious anaemia (PA) is associated with a higher risk of gastrointestinal malignancies. BSG guidance suggests baseline gastroscopies for individuals aged >=50 years with laboratory evidence of PA, with surveillance offered to those with high-risk chronic atrophic gastritis.1 Shrewsbury and Telford NHS Trust is not currently offering gastroscopies to patients with PA. Our aim was to identify cases of PA suitable for gastroscopies in line with BSG guidance, followed by implementation of pathways for prospective detection of similar future cases. Methods A list of patients who tested positive for intrinsic factor antibodies (IF Ab) or gastric parietal cell (GPC Ab) between 2017-2022 was obtained from the laboratory. Patients aged 50-70y were stratified into groups as follows: Positive IF Ab considered confirmed PA; positive GPC Ab with low B12 levels considered probable PA; positive GPC with historically normal B12 and no anaemia considered unlikely to be PA. Patients who had gastroscopy for any indication in the last 5 years were excluded. Results 50 cases that met the criteria for confirmed or probable PA were deemed suitable for baseline gastroscopy. Pathway for these patients will be agreed with the hospital governance and GP liaison teams and standard letters and information leaflets will be devised. Confirmed cases will be offered gastroscopy, while probable cases will be offered further testing with IF Ab. If diagnosis is confirmed, gastroscopy will be offered, whereas if IF Ab is negative, no further action taken if the B12 deficiency responds to oral supplementation. For prospective detection of future cases, clinical text will be added in all biochemistry reports with low B12 levels prompting clinicians to consider IF Ab testing if PA is possible in clinical context, with referral to gastroenterology for confirmed cases. Cases tested before 2017 who fit the above criteria will be identified. Conclusions The number of confirmed or probable cases of PA in Shropshire is relatively small and sets a realistic target for offering gastroscopies in line with BSG guidance. Similar initiatives across other trusts could identify cases of PA in the respective regions that could be suitable for baseline or surveillance gastroscopies, with prospective detection of future cases leading to better overall management of PA.

The Advanced Colonoscopy Skills Training Required For NHS Bowel Cancer Screening Accreditation: The Outcomes Of An Integrative Literature Review (2023)

Type of publication:
Conference abstract

Author(s):
*Brayford P.

Citation:
Gut. Conference: Annual Meeting of the British Society of Gastroenterology, BSG 2023. Liverpool United Kingdom. 72(Supplement 2) (pp A169), 2023. Date of Publication: June 2023.

Abstract:
Introduction NHS Bowel cancer screening colonoscopists are required to undertake accreditation for which there are well defined standards, but training to achieve these skills has not been clearly determined. An Integrative Review aimed to identify the training required for independent colonoscopists to develop the advanced skills necessary to achieve Bowel Cancer Screening Accreditation (BCSA). The findings were utilised to develop a training plan which could support independent colonoscopists achieve BCSA. Methods The Integrative Review (IR) utilised the secondary research process described by Whittemore and Knafl (2005) to synthesise and analyse a range of methodologically diverse studies. Key stages of this process included problem identification, literature search, data evaluation, data analysis, conclusion drawing and presentation. Electronic databases including CINHAL, MEDLINE and PubMed were searched in September 2020. The inclusion criteria were English language literature focused on training in the advanced colonoscopy skills from 2012 onwards, excluding beginner colonoscopy training. Results In total this generated 3548 papers of which 3476 were excluded. The full text of seventy-seven papers were screened, identifying twenty-three methodologically diverse papers, meeting the inclusion/exclusion criteria for critical evaluation and analysis within the IR. Five broad themes were found to contribute to the development of the advanced colonoscopy skills required for BCSA-See figure 1. Conclusions It was clear from the IR that training in polyp related skills and knowledge was vital for successful BCSA. In addition, selecting motivated, meticulous colonoscopists and focusing on individual learning needs along with utilisation of audit and feedback all contribute to skill development for BCSA. The IR findings were utilised to develop evidence based individual, local, regional and national recommendations to assist with the advanced colonoscopy skill development necessary for BCSA.

Rectal cancer services - is it time for specialization within units? (2023)

Type of publication:
Journal article

Author(s):
Maxwell-Armstrong, Charles; *Cheetham, Mark; Branagan, Graham; Davies, Justin; Davies, Mike; Eardley, Nicola; Hancock, Laura; Harikrishnan, Athur; McArthur, David; Siddiqui, Shahab; Tiernan, Jim; Torkington, Jared.

Citation:
Colorectal Disease. 25(7):1332-1335, July 2023

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