Introduction

Intestinal dysbiosis is associated with violating both the quantitative and qualitative intestinal microbiome composition (IM). It accompanies different gastrointestinal disorders, including non-celiac gluten sensitivity (NCGS) and celiac disease (CD). A gluten-free diet is the only existing treatment for CD and NGCC. One of the questions of interest is the characteristics of the IM of patients with gluten-related diseases (GRDs) and its relationship with diet therapy.

Aims & Methods

To determine the IM composition of patients with CD and NCGS who adhere to the agliadin diet and compare it to the IM composition of people without GRDs. The study included 25 adults: 14 (56%) with CD and 11 (44%) with NCGS; all were on agliadin diet. The control group (CG) included 24 people without gluten-sensitive pathology or gastrointestinal diseases. We determined the faecal content of the Bacteroidetes, Firmicutes, and Actinobacteria phylae and the rest bacterial desoxyribose nucleic acid DNA ("other" indicator) using the real-time polymerase chain reaction (real-time PCR).

Results

The Firmicutes content was 53.47 (IQR 49.98-57.21) % in CD patients (p<0,05 with CG), 53.0 (IQR 47.13-71.95) % in NCGS patients (p>0.1 with other groups) and 69.89 (IQR 58.58- 74.1) % of CG. Bacteroidetes content was 28.4 (IQR 6.58-39.28) % in CD patients, 24.98 (IQR 8.83-31.04) in NCGS patients (p>0.1 with CD), and 6.83 (IQR 3.69-9.22) in the CG (p<0.05 with GRDs). The Actinobacteria content was 4.8 (IQR 3.73 - 7.2) % in CD patients, 5.37 (IQR 3.89-8.56) % in NCGS patients (p>0.1 with CD), and 11.36 (IQR 7.07- 15.34) in the CG (p<0.01 with GRDs). The Firmicutes/Bacteroidetes (F/B) ratio was 1,996 (IQR 1.27-8.15) in CD patients, 2.0 (IQR 1.63-8.25) in NCGS patients (p>0.1 with CD), and 9.986 (IQR 6.37-18.80) in CG (p<0.05 with GRDs). The content of "other" types of IM was 15.39 (IQR 7.25-23.06) in CD patients, 13.78 (IQR 9.48-16.05) in NCGS patients, and 13.66 (IQR 8.43-17.78) in CG. This indicator had no significant difference (p> 0.99) between all three groups.

Conclusion

We found significant IM changes among patients with CD and NCGS, expressed in an increase in the Bacteroidetes content with a parallel decrease in the content of Firmicutes and Actinobacteria. The most significant changes were in Actinobacteria content, a less significant - the Firmicutes/Bacteroidetes ratio. Meanwhile, we did not find a difference in IM composition between CD and NCGS groups. Thus, detected intestinal microbiome changes are most likely to be a consequence of dietary features of such patients, namely the side effect of keeping an agliadin diet.

Introduction

There are around 12,400 new cases of head and neck cancer diagnosed in the UK each year. It is the 8^th most common cancer in the UK and incidence rates are projected to rise by 3% over the next two decades. Between 33 and 69% of patients with Head and Neck cancer will require enteral feeding via a gastrostomy tube to support their nutrition and hydration during treatment. Percutaneous endoscopic gastrostomy (PEG) is often the preferred method of placement of the gastrostomy tube and is generally considered safe but malignant seeding of the tumour to the PEG site is a rare complication. It has been reported that rate of metastasis at the PEG site is between 0.5-3%.

Aims & Methods

We carried out a retrospective chart review of all patients undergoing PEG insertion at the Bristol Royal Infirmary between January 2015 and December 2021. The primary aim was to determine the rate of PEG site metastases at our centre. Demographic data were collected, as well as cancer type and stage, details of disease progression.

Results

A total of 284 patients underwent PEG insertion during the period of data collection. Of these, 204 patients had their gastrostomy inserted for a head and neck cancer indication. All PEG tubes were put in using the ‘pull’ method. 2 patients were identified as having abdominal metastatic disease and these cases were reviewed in greater detail. On further review these 2 patients were not found to have malignant spread to the PEG site specifically, but more general peritoneal disease, unrelated to the method of gastrostomy insertion. For both patients, the abdominal disease was in the context of widespread metastatic disease. There were therefore no cases of PEG site metastases at our centre between January 2015 and December 2021 (0/204, 0%).

Conclusion

Our data suggests that PEG is a safe method of gastrostomy insertion for head and neck cancer patients, without significant risk of tumour seeding to the PEG site.

References

https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/head-and-neck-cancers#heading-Five
Greaves JR. Head and Neck Cancer Tumor Seeding at the Percutaneous Endoscopic Gastrostomy Site. Nutr Clin Pract. 2018 Feb;33(1):73-80.
Huang AT, Georgolios A, Espino S, et al. Percutaneous endoscopic gastrostomy site metastasis from head and neck squamous cell carcinoma: case series and literature review. J Otolaryngol Head Neck Surg. 2013 Feb 28;42(1):20.
Vamsi, Arthi; Ragunathan, Karthik; Puli, Srinivas. Malignant Seeding Following Percutaneous Endoscopic Gastrostomy Placement in Head and Neck Cancer: Review of Literature: 1900. American Journal of Gastroenterology 109():p S563, October 2014.

Disclosure

No conflicts of interest to declare.

Introduction

Initial reports suggested a high mortality associated with peri-operative COVID-19 infection resulting in delayed surgery and a global change in surgical pathways. The impact of COVID-19 variants and vaccinations on surgical outcomes is yet to be described.

Aims & Methods

We aimed to define the risk of COVID-19 infection in the 30 days following surgery and the associated mortality. With the approval of NHS England we identified all registered adult patients in an OpenSAFELY-TPP primary care general practice within England whilst having an abdominal, obstetric, orthopaedic, thoracic or vascular procedure defined using OPCS codes between 01/02/2020 and 01/03/2022.COVID vaccinations and COVID waves were defined. Crude 30 day risks were calculated using Kaplan Meier curves. A competing risks Cox proportional survival analysis was used to adjust the cumulative risk of COVID-19 infection by the competing risk of death and subsequent non COVID-19 emergency readmissions.
Primary care records managed by the GP software provider TPP were linked to ONS death data, Hospital Episodes Statistics, and Second Generation Surveillance System Public Health England test data through OpenSAFELY. All data were linked, stored and analysed securely within the OpenSAFELY platform: https://opensafely.org/. Data include pseudonymised data such as coded diagnoses, medications and physiological parameters. No free text data are included. All code is shared openly for review and re-use under MIT open license https://github.com/opensafely/PostOpCovid. Detailed pseudonymised patient data is potentially re-identifiable and therefore not shared.
This study was approved by the Health Research Authority [REC reference 21/EE/0278] by the East of England Research Ethics Committee.

Results

We identified 1,213,890 patients within the study period who underwent at least one surgical procedure. Following surgery 11,950 (0.9%) patients developed COVID-19 infection within 30 days. Post-operative COVID infections were greatest in wave 4 with 2.5% of patients having a post-operative infection. Adjusting for all factors post-operative COVID infection risk was 4.9 (aHR 4.88 95% CI 4.65-5.12) fold greater in the fourth wave compared to the first wave.
Within 90 days of surgery there were 820 (0.06%) deaths. A recent COVID infection increased crude morality to 1.42%, and a post-operative COVID infection increased crude mortality to 1.82%. The risk of death reduced following a first and second vaccination (aHR 0.11 95% CI 0.09-0.13). A recent COVID infection (7-42 days prior to admission) increased mortality 4 fold (aHR 3.84 95% CI 3.31-4.45) and a post-operative COVID infection increased mortality 8 fold (aHR 8.49 95% CI 7.6-9.48) compared to those without a COVID-19 infection. This increased 90 day mortality risk was highest in the second wave following a post-operative COVID infection, but then decreased to the non-covid baseline for both emergency and elective procedures in the 3^rd and 4^th waves.

Conclusion

The risk of post-operative COVID infection is low but has increased as strains have been become more transmissible. The absolute risk of death following peri-operative COVID-19 infection is greater than those who have not had infection however this risk has become attenuated during the latter waves of the pandemic.

Acknowledgements: We are very grateful for all the support received from the TPP Technical Operations team throughout this work, and for generous assistance from the information governance and database teams at NHS England and the NHS England Transformation Directorate.

Disclosure

None to declare

Introduction

Liver biopsy remains the gold standard for fibrosis diagnosis and liver elastography is an accurate method for non-invasive evaluation, although often unavailable. FIB-4, a fibrosis index based on age, AST, ALT and platelet count, is increasingly used to predict advanced fibrosis, mostly in primary care. There are different cut-offs, however considering Non-Alcoholic Fatty Liver Disease (NAFLD) patients FIB-4 <1.30 was able to exclude advanced fibrosis, while FIB-4 >2.67 presented good positive predictive value. For populations older than 65years old, a cut off of 2.0 was advocated.

Aims & Methods

We aim to evaluate this tool on a tertiary hospital.
Using a tertiary hospital database of blood workup we selected the 3575 blood collections in ambulatory patients between 1^st-31^st august 2021 with laboratory data for FIB-4 calculation. We excluded patients under 18 years, those followed on Haematology, and those with AST or ALT >100 UI/L. We considered only the first blood collection for each patient in this period. On our study we compared patients according to FIB-4 value respective of their association with chronic renal disease, dyslipidaemia and altered glucidic metabolism. We investigated what percentage of those with FIB-4 >1.3 were followed on Gastroenterology.

Results

During the study period, among 3213 blood collections that fulfilled the criteria, 1290 (40.1%) had a FIB-4 >1.3. Male gender (51.4% vs 37.7%, p<0.001) and older age (70.1 vs 49.4, p>0.001) were significantly associated with FIB-4 >1.3. FIB-4 >1.3 associated with glomerular filtration rate (GFR) <90ml/min/1.73m² (p<0.001), chronic renal disease (GFR<60ml/min/1.73m²) (p<0.001), serum cholesterol >200mg/dL (p=0.22) and serum glucose >130 mg/dL. (p=0.003). There was no difference in ALT values (p=0.513) but on AST (p=0.001). Only 12.9% of patients with FIB-4>1.3 had a Gastroenterology appointment in our institution.
On a subgroup analysis for patients older than 65 years old, 405 (31.4%) patients had a FIB4 >2.0 among 1286. Male gender (48.8% vs 57.1%, p=0.005) and age (73.3 vs 80.0, p=0.005) significantly associated with FIB-4 >2.0. FIB-4>2.0 associated with GFR <90ml/min/1.73m² (p<0.001), GFR <60ml/min/1.73 (p=0.003) and cholesterol >200mg/dL (p=0.001) but no difference on glucose >130mg/dL (p=0.192). There was no difference in ALT values (p=0.695) but on AST (p=0.001).

Conclusion

Using the lower cut-off for FIB4, it is frequently elevated in referrals to a tertiary hospital. FIB-4 is associated with declining GFR and disturbances on lipid and glucose metabolism. Awareness of FIB-4 tool, may help recognizing the risk of advanced liver disease in patients and suspect renal disease or diabetes, as part of NAFLD phenotype.

Introduction

Making an Inflammatory Bowel Disease (IBD) diagnosis can be challenging as symptoms may mimic more common conditions such as irritable bowel syndrome or haemorrhoids. This can lead to delays in IBD diagnosis, which can be associated with the need for more complex treatment or surgery.

Aims & Methods

This study aims to quantify the time to diagnosis for IBD and examine associations with patient characteristics and faecal calprotectin (FC) and its impact on surgery and emergency hospital admissions.
A retrospective cohort study was conducted using Clinical Practice Research Datalink (CPRD AURUM) from 1st Jan 2007 to 31st Dec 2019. Adult patients were followed from when they first presented with symptoms, signs, test results or alternative diagnosis potentially related to IBD in primary care in the 3 year period prior to IBD diagnosis. The association between patient level factors and FC with the time to IBD diagnosis were examined using logistic regression analysis. We examined changes in time to IBD diagnosis over the 10 year study period. The association of time to IBD diagnosis with IBD related surgeries and emergency admissions was also examined.

Results

Of 28,092 IBD patients: 60.0% ulcerative colitis (UC) and 40.0% Crohn’s disease (CD). Median age 43(IQR 30-58) years; 51.9% female. Median time to diagnosis 15.6 (IQR 4.3- 28.1) months; UC 13.8 (3.2-27.1) months and CD 17.8 (6.5-29.2) months.
Factors associated with over 12 months to IBD diagnosis: female ((OR 1.64(95%CI 1.56-1.72)); Black (1.45(1.20-1.76)) or Asian ethnicity (1.55(1.40-1.72); older age compared to 18-30 years (>70 1.14(1.03-1.27)); obesity (1.09(1.01-1.17)); smoking (1.13(1.06-1.20)); lower socioeconomic status (1.15 (1.06-1.25)); anxiety (1.15(1.07-1.24)); depression (1.19(1.11-1.28)); non-steroidal anti-inflammatory drugs (NSAIDs) (1.45(1.33-1.59)); loperamide (1.56 (1.31-1.86)) and increasing comorbidity Charlson score >2 (1.46(1.32-1.61)).
Only 11.3% of IBD patients had FC testing. Time to diagnosis from FC date was median 4.0 (IQR 1.8- 8.8) months. Higher FC levels were associated with decreasing time to IBD diagnosis: 500-1000 (0.76 (0.66-0.89)),>1000 (0.61(0.51-0.72)).
No improvement in time to IBD diagnosis was observed over the last 10 years: 2010-2011 (14.4 (3.6 -27.6) months) compared to 2018-2019 median (15.6 (4.8-28.8) months).
Patients with time to diagnosis in highest quartile were at lower risk of surgery within a year of diagnosis (HR 0.91(0.81-1.03) but had more IBD related emergency admissions after diagnosis (IRR 1.06 (1.01-1.11).

Conclusion

Longer times to diagnoses were associated with females, minority ethnicities, increasing age, increasing comorbidity, deprivation, obesity, anxiety, depression, NSAIDs and loperamide use. Faecal calprotectin testing reduced time to diagnoses. Higher number of IBD related emergency admissions were observed in patients with a prolonged time to diagnosis.

Disclosure

No conflict of interest to declare

Introduction

There are no prediction models for a diagnosis of inflammatory bowel disease (IBD) in primary care. Our aim was to develop an IBD risk prediction tool to reduce the length of time patients have undiagnosed IBD symptoms and improve IBD clinical outcomes.

Aims & Methods

We developed and internally validated a risk prediction tool for the diagnosis of IBD, ulcerative colitis (UC) and Crohn’s disease (CD).
A population-based retrospective open cohort study using Clinical Practice Research Datalink (CPRD) database was undertaken between 1st January 2010 and 31st December 2019 of all the patients aged 18 years or older. Patients were followed from first presentation with lower gastrointestinal (GI) symptoms potentially related to IBD to IBD diagnosis. Candidate predictors were chosen based on clinical and substantive knowledge. Cox proportional hazards regression with backward elimination was used for model development of IBD, UC and CD risk prediction models. The predictive performance of the models was assessed using discrimination (C-statistic). Internal validation using 1000 bootstrap sampling repetitions was used to estimate the optimism-corrected measures of predictive performance.

Results

Of 2,056,398 patients with lower GI symptoms: 11,192 patients had an IBD diagnosis (7033 UC (62.8%) and 4138 CD (37.0%)). The final IBD model included demographic factors (age, sex, ethnicity, smoking, index of multiple deprivation, body mass index, Charlson comorbidity index, loperamide use) co-existing conditions (anxiety, depression, irritable bowel syndrome (IBS), haemorrhoids), extraintestinal (EIM) manifestations (mouth ulcers, ophthalmic, primary sclerosing cholangitis, dermatological), laboratory investigations (low haemoglobin (Hb), low Mean Corpuscular volume (MCV), low albumin, low ferritin, raised C-reactive protein (CRP), raised Erythrocyte Sedimentation Rate (ESR), raised calprotectin level). The UC model included all above except mouth ulcers, IBS, ophthalmic EIM. Depression and ferritin were excluded in the CD model though low vitamin B12 level was included. The risk score for each patient was the sum of individual risk factors. In the development dataset, models showed moderate discrimination. For the IBD prediction tool: C-statistic 0.71 (95% CI 0.70-0.71),UC prediction tool: C-statistic 0.70 (95% CI 0.69-0.70) and CD prediction tool: C-statistic 0.75 (95% CI 0.74-0.76). The C-statistics of the models showed that the IBD, UC and CD prediction tools reliably differentiated patients with and without IBD,UC and CD respectively.

Conclusion

A risk score of patient demographics, symptoms and investigations performs well for IBD,UC and CD and may help in prioritising suspected IBD referrals in symptomatic subjects in primary care.

Disclosure

No conflict of interest to declare

Introduction

Advances in medical management of Crohn’s disease (CD) have improved disease outcomes; however, significant gaps remain. Approximately 30% of patients experience primary non-response to induction therapy with biologics, and over 40% will experience loss of response. There is an urgent need to identify new adjunct therapies, including diet, that can alter the disease course. Dietary patterns characterized by increased intakes of fibre, fruit, vegetables and decreased intakes of processed foods, sugar and omega-6 fatty acids are linked to a reduced prevalence of CD and decreased biomarkers of intestinal and systemic inflammation; however, the effects upon mucosal inflammation are unknown in patients who have lost response to usual medical treatments. We developed the CD Therapeutic Dietary Intervention (CD-TDI), a novel dietary approach incorporating best practices and current evidence to determine its therapeutic potential in reducing inflammation in patients with active CD who have lost response to their usual therapies.

Aims & Methods

This 13-week RCT aimed to explore the efficacy of the CD-TDI compared with conventional management (CM) to reduce clinical disease activity (Harvey-Bradshaw Index (HBI) <5) and reduce mucosal inflammation, as measured by fecal calprotectin (FCP) in mild-to-moderately active luminal CD. Patients with mild to moderately active disease, determined by endoscopic, cross-sectional imaging or FCP >100 ug/g, on stable medical therapy 8 weeks prior to recruitment were eligible to participate (n=28). Upon randomization, the CD-TDI group (n=16) met virtually with a registered dietitian trained in the CD-TDI protocol weekly for 13 weeks. Participants assigned to CM (n=12) followed their habitual diet and met with the same registered dietitian as participants in the CD-TDI group at week 0 (W0) and week 13 (W13) to capture their dietary recall. FCP, HBI, and C-reactive protein (CRP) were assessed at W0 and W13.

Results

Twenty-eight participants (53% females, age 40 years (IQR:31-55); BMI 27 kg/m² (IQR:24-31)) were enrolled. Medical therapy did not differ between groups, with 54% (15/28) of participants receiving no drug therapy, 29% (8/28) 5-ASA monotherapy, 21% (6/28) biologic therapy, 11% (3/28) corticosteroids or 14% (4/28) immunomodulators. At W0, the FCP, HBI and CRP did not differ significantly between groups. In the CD-TDI group, FCP decreased significantly from 130 ug/g (IQR: 38-411) at W0 to 72 ug/g (IQR:3-153) at W13 (p= 0.01) and significantly differed between the CM group at W13 (p=0.04). In a sub-group analysis (n=11) of participants with FCP >250 ug/g at W0, at W13 the FCP decreased significantly from 632 ug/g (IQR: 356-1013) to 166 ug/g, (IQR:52-701) (p=0.06) within the CD-TDI group, however, this same trend was not observed in the CM (W0:337 ug/g IQR:324-1013 vs. W13:431 ug/g, IQR:46-1770, p=0.69). At W13, between-group differences in the CRP were found between the CD-TDI group (1.0 mg/L, IQR:0.6-2.4) and the CM group (4.5 mg/L, IQR:2.6-13.0) (p=0.002). The CD-TDI group experienced a significant decrease in HBI from W0 to W13 (W0: 3.0, IQR:1.0-5.3; W13: 2.0, IQR:0-3.0; p=0.05), however, this was not observed in the CM group.

Conclusion

At W13, the CD-TDI significantly decreased clinical and biochemical markers of inflammation in patients with mild-to-moderately active CD. This preliminary analysis suggests that CD-TDI could be a potential adjunct management strategy for reducing inflammation in CD. We hope to confirm these promising results with an adequately powered sample.