Reduced survival after upper gastrointestinal bleed endoscopy in the COVID-19 era is a secondary effect of the response to the global pandemic: a retrospective cohort study.

OBJECTIVE: The COVID-19 pandemic has placed increased strain on healthcare systems worldwide with enormous reorganisation undertaken to support 'COVID-centric' services. Non-COVID-19 admissions reduced secondary to public health measures to halt viral transmission. We aimed to understand the impact of the response to COVID-19 on the outcomes of upper gastrointestinal (UGI) bleeds. DESIGN/METHODS: A retrospective observational multicentre study comparing outcomes following endoscopy for UGI bleeds from 24 March 2020 to 20 April 2020 to the corresponding dates in 2019. The primary outcome was in-hospital survival at 30 days with secondary outcomes of major rebleeding within 30 days postprocedure and intervention at the time of endoscopy. RESULTS: 224 endoscopies for 203 patients with UGI bleeds were included within this study. 19 patients were diagnosed with COVID-19. There was a 44.4% reduction in the number of procedures performed between 2019 and 2020. Endoscopies performed for UGI bleeds in the COVID-19 era were associated with an adjusted reduced 30-day survival (OR 0.25, 95% CI 0.08-0.67). There was no increased risk of major rebleeding or interventions during this era. Patients with COVID-19 did not have reduced survival or increased complication rates. CONCLUSION: Endoscopy for UGI bleeds in the COVID-19 era is associated with reduced survival. No clear cause has been identified but we suspect that this is a secondary effect of the response to the COVID-19 pandemic. Urgent work is required to encourage the public to seek medical help if required and to optimise patient pathways to ensure that the best possible care is provided.

Clinical Characteristics and Predictors of Outcomes of Hospitalized Patients With Coronavirus Disease 2019 in a Multiethnic London National Health Service Trust: A Retrospective Cohort Study.

BACKGROUND: Emerging evidence suggests ethnic minorities are disproportionately affected by coronavirus disease 2019 (COVID-19). Detailed clinical analyses of multicultural hospitalized patient cohorts remain largely undescribed. METHODS: We performed regression, survival, and cumulative competing risk analyses to evaluate factors associated with mortality in patients admitted for COVID-19 in 3 large London hospitals between 25 February and 5 April, censored as of 1 May 2020. RESULTS: Of 614 patients (median age, 69 [interquartile range, 25] years) and 62% male), 381 (62%) were discharged alive, 178 (29%) died, and 55 (9%) remained hospitalized at censoring. Severe hypoxemia (adjusted odds ratio [aOR], 4.25 [95% confidence interval {CI}, 2.36-7.64]), leukocytosis (aOR, 2.35 [95% CI, 1.35-4.11]), thrombocytopenia (aOR [1.01, 95% CI, 1.00-1.01], increase per 109 decrease), severe renal impairment (aOR, 5.14 [95% CI, 2.65-9.97]), and low albumin (aOR, 1.06 [95% CI, 1.02-1.09], increase per gram decrease) were associated with death. Forty percent (n = 244) were from black, Asian, and other minority ethnic (BAME) groups, 38% (n = 235) were white, and ethnicity was unknown for 22% (n = 135). BAME patients were younger and had fewer comorbidities. Although the unadjusted odds of death did not differ by ethnicity, when adjusting for age, sex, and comorbidities, black patients were at higher odds of death compared to whites (aOR, 1.69 [95% CI, 1.00-2.86]). This association was stronger when further adjusting for admission severity (aOR, 1.85 [95% CI, 1.06-3.24]). CONCLUSIONS: BAME patients were overrepresented in our cohort; when accounting for demographic and clinical profile of admission, black patients were at increased odds of death. Further research is needed into biologic drivers of differences in COVID-19 outcomes by ethnicity.

In-hospital mortality is associated with inflammatory response in NAFLD patients admitted for COVID-19.

BACKGROUND & AIMS: Although metabolic risk factors are associated with more severe COVID-19, there is little evidence on outcomes in patients with non-alcoholic fatty liver disease (NAFLD). We here describe the clinical characteristics and outcomes of NAFLD patients in a cohort hospitalised for COVID-19. METHODS: This study included all consecutive patients admitted for COVID-19 between February and April 2020 at Imperial College Healthcare NHS Trust, with either imaging of the liver available dated within one year from the admission or a known diagnosis of NAFLD. Clinical data and early weaning score (EWS) were recorded. NAFLD diagnosis was based on imaging or past medical history and patients were stratified for Fibrosis-4 (FIB-4) index. Clinical endpoints were admission to intensive care unit (ICU)and in-hospital mortality. RESULTS: 561 patients were admitted. Overall, 193 patients were included in the study. Fifty nine patients (30%) died, 9 (5%) were still in hospital, and 125 (65%) were discharged. The NAFLD cohort (n = 61) was significantly younger (60 vs 70.5 years, p = 0.046) at presentation compared to the non-NAFLD (n = 132). NAFLD diagnosis was not associated with adverse outcomes. However, the NAFLD group had higher C reactive protein (CRP) (107 vs 91.2 mg/L, p = 0.05) compared to non-NAFLD(n = 132). Among NAFLD patients, male gender (p = 0.01), ferritin (p = 0.003) and EWS (p = 0.047) were associated with in-hospital mortality, while the presence of intermediate/high risk FIB-4 or liver cirrhosis was not. CONCLUSION: The presence of NAFLD per se was not associated with worse outcomes in patients hospitalised for COVID-19. Though NAFLD patients were younger on admission, disease stage was not associated with clinical outcomes. Yet, mortality was associated with gender and a pronounced inflammatory response in the NAFLD group.

Biomarker measurement in non-invasively sampled colorectal mucus as a novel approach to colorectal cancer detection: screening and triage implications.

BACKGROUND: Faecal tests are widely applied for colorectal cancer (CRC) screening and considered for triaging symptomatic patients with suspected CRC. However, faecal tests can be inconvenient, complex and expensive. Colorectal mucus (CM) sampled using our new patient-friendly non-invasive technique is rich in CRC biomarkers. This study aimed to evaluate diagnostic accuracy of CRC detection by measuring protein biomarkers in CM. METHODS: Colorectal mucus samples were provided by 35 healthy controls, 62 CRC-free symptomatic patients and 40 CRC patients. Biomarkers were quantified by ELISA. Diagnostic performances of haemoglobin, C-reactive protein, tissue inhibitor of metalloproteinases-1, M2-pyruvate kinase, matrix metalloproteinase-9, peptidyl arginine deiminase-4, epidermal growth factor receptor, calprotectin and eosinophil-derived neurotoxin were assessed using receiver operating characteristic (ROC) curve analysis. RESULTS: Colorectal mucus haemoglobin was superior compared to other biomarkers. For haemoglobin, the areas under the curve for discriminating between CRC and healthy groups ('screening') and between CRC and symptomatic patients ('triage') were 0.921 and 0.854 respectively. The sensitivity of 80.0% and specificities of 94.3% and 85.5% for the two settings respectively were obtained. CONCLUSIONS: Haemoglobin quantification in CM reliably detects CRC. This patient-friendly approach presents an attractive alternative to faecal immunochemical test; however, the two methods need to be directly compared in larger studies.

Colorectal cancer detection by biomarker quantification in noninvasively collected colorectal mucus: preliminary comparison of 24 protein biomarkers.

OBJECTIVES: Noninvasive colorectal cancer detection and screening remain global diagnostic challenges because the existing stool tests either lack sensitivity or are complex and expensive. Moreover, colorectal cancer screening uptake is low due to stool sampling inconvenience. We have developed a simple and patient-friendly noninvasive technique for collecting highly informative colorectal mucus. In this study, we aimed to comparatively assess a range of candidate biomarkers in colorectal mucus samples for colorectal cancer detection. METHODS: The study included 17 patients with colorectal cancer and 35 healthy controls, who provided noninvasively collected colorectal mucus samples. Protein biomarker quantification in these samples by enzyme-linked immunosorbent assays allowed comparing diagnostic performances of 24 candidate biomarkers that comprised haemoglobin, D-dimer, M2-pyruvate kinase, carcinoembryonic antigen, C-reactive protein, calprotectin, eosinophil-derived neurotoxin, protein S100A12, tumour necrosis factor α, clusterin, soluble cytokeratin 18, caspase-cleaved cytokeratin 18, citrullinated histone H3, peptidyl arginine deiminase 4, epidermal growth factor, epidermal growth factor receptor, matrix metalloproteinase 9, tissue inhibitor of metalloproteinase 1, periostin, vascular endothelial growth factor A, vascular endothelial growth factor receptor 1, vascular cell adhesion molecule 1, intercellular adhesion molecule 1 and mucin 2. Tested biomarkers were ranked for colorectal cancer detection efficiency using receiver operating characteristic curve analysis. RESULTS: High area under the curve values between 0.943 and 0.768 were observed for haemoglobin, tissue inhibitor of metalloproteinase 1, M2-pyruvate kinase, peptidyl arginine deiminase 4, C-reactive protein, matrix metalloproteinase 9, epidermal growth factor receptor, eosinophil-derived neurotoxin and calprotectin. CONCLUSION: Quantification of protein biomarkers in noninvasively collected samples of colorectal mucus certainly allows detecting colorectal cancer. Further clinical evaluation of the optimal biomarkers identified by this study is needed.

Health concerns associated with travelling with inflammatory bowel disease (IBD): a questionnaire survey.

When travelling, patients with inflammatory bowel disease (IBD) have a higher risk of morbidity. We identified barriers to travel, specific health concerns and several areas for service improvement among patients. In total, 136 patients were given a 32-question service improvement questionnaire. Of these, 89% travelled abroad, 30% reported that IBD limited travel and 40% said it affected choice of destination. Fourty-seven percent of patients travelled abroad without health insurance and 7% were refused. Seventy-eight percent wanted pre-travel advice from doctors in the future. Popular service improvement options included providing written prescriptions (91%) and management plans (75%). Sixty-three percent of patients were unaware of needing to avoid live vaccines while on immunosuppressants. Ninety-two percent were unaware that high altitudes could precipitate flares; 27% travelled abroad to high-altitude destinations, of which 46% subsequently had flare-ups. Existing IBD travel services remain unknown such as the 'Can't wait' card (72%) and 'IBD passport' (96%). Service improvements in the IBD clinic need to be implemented to facilitate safer travel overseas.

Emerging Biomarkers for the Diagnosis and Monitoring of Inflammatory Bowel Diseases.

There is currently no single test available to confidently diagnose cases of inflammatory bowel disease (IBD). Physicians rely on a number of diagnostic tools, including clinical evaluation, serum testing, and imaging, which are used on conjunction with endoscopic evaluation. It is often difficult to determine whether patients with abdominal pain and change in bowel habit have functional bowel symptoms or whether they have a true diagnosis of IBD. Even once a diagnosis of IBD has been made, a significant proportion of patients are labeled with the term "indeterminate colitis" where histological sampling cannot confidently subclassify patients as either Crohn's or ulcerative colitis. Colonoscopy is an inconvenient and uncomfortable test for most patients. In addition, it is not without serious risks of perforation, as well as risks which can be associated with sedation and analgesia given during the procedure. The use of biomarkers to aid in the diagnosis, subclassification, and monitoring of IBD is an ever expanding area. In this review, we have concentrated on noninvasive biomarkers of IBD, because these are more acceptable to patients and easier to perform in everyday clinical practice. We will first touch on those biomarkers currently well established and in wide clinical use, such as C-reactive protein, erythrocyte sedimentation rate. Faecal calprotectin and their use in the diagnosis of IBD. Following on, we will review more novel biomarkers and their use in subclassification and monitoring of IBD, including a variety of antibodies, genetics, and microRNAs, as well as touching on metabolomics.

Emerging role of novel biomarkers in the diagnosis of inflammatory bowel disease.

There is currently no gold standard test for the diagnosis of inflammatory bowel disease (IBD). Physicians must rely on a number of diagnostic tools including clinical and endoscopic evaluation as well as histologic, serologic and radiologic assessment. The real difficulty for physicians in both primary and secondary care is differentiating between patients suffering from functional symptoms and those with true underlying IBD. Alongside this, there is always concern regarding the possibility of a missed, or delayed diagnosis of ulcerative colitis (UC) or Crohn's disease. Even once the diagnosis of IBD has been made, there is often uncertainty in distinguishing between cases of UC or Crohn's. As a consequence, in cases of incorrect diagnosis, optimal treatment and management may be adversely affected. Endoscopic evaluation can be uncomfortable and inconvenient for patients. It carries significant risks including perforation and in terms of monetary cost, is expensive. The use of biomarkers to help in the diagnosis and differentiation of IBD has been increasing over time. However, there is not yet one biomarker, which is sensitive of specific enough to be used alone in diagnosing IBD. Current serum testing includes C-reactive protein and erythrocyte sedimentation rate, which are cheap, reliable but non-specific and thus not ideal. Stool based testing such as faecal calprotectin is a much more specific tool and is currently in widespread clinical use. Non-invasive sampling is of the greatest clinical value and with the recent advances in metabolomics, genetics and proteomics, there are now more tools available to develop sensitive and specific biomarkers to diagnose and differentiate between IBD. Many of these new advances are only in early stages of development but show great promise for future clinical use.

Burden of irritable bowel syndrome in an increasingly cost-aware National Health Service.

BACKGROUND: The National Health Service (NHS) is faced with increasing cost pressures that make the efficient use of resources paramount. Irritable bowel syndrome (IBS) places a large burden on the NHS as it has been estimated that at least 12% of the UK population is affected. However, poor clinical coding makes accurate assessment of this burden challenging. OBJECTIVE: To calculate primary-care prescribing and both hospital outpatient and admission costs associated with the management of IBS in England. DESIGN AND MAIN OUTCOME MEASURES: Hospital Episode Statistics data for 2012-2013 for all clinical commissioning groups in England were analysed to calculate the tariff cost of IBS. Prescribing analysis and cost tabulation (PACT) data for this period were also analysed. RESULTS: In 2012-2013, there were 1 219 961 outpatient attendances in gastroenterology and colorectal surgery specialties. Despite this, only 1982 patients were recorded with IBS-specific codes, with a total estimated tariff cost of £812 336. In addition, 28 849 patients were recorded with IBS-related symptom codes at a cost of £11 002 874. In 2011-2012, there were 658 698 diagnostic lower gastrointestinal endoscopies at a tariff cost of £16 967 670 4. Of these, 323 752 (49%) had no further follow-up in secondary care over the subsequent 12 months. PACT data indicated that £44 977 959 and £25 582 752, respectively, were spent on selected laxatives and antispasmodics commonly used to treat IBS in primary care. CONCLUSIONS: Better diagnosing, through improved clinical coding and standardisation of diagnostic criteria, is required to more accurately assess the true burden and allow optimal management of IBS.