The Diagnostic Utility of Volatile Organic Compounds in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Volatile organic compounds [VOCs] show promise as potential biomarkers of for ulcerative colitis and Crohn's disease, two chronic, idiopathic, gastrointestinal disorders with diagnostic and management challenges. Non-invasive biomarkers aid early diagnosis and management. In this study we review studies of diagnostic accuracy of VOCs in inflammatory bowel disease. METHODS: A systematic search was carried out on the Pubmed and Scopus databases; with 16 studies reviewed and meta-analysis carried out on 10. RESULTS: Meta-analysis of 696 inflammatory bowel disease [IBD] cases against 605 controls revealed a pooled sensitivity and specificity of 87% (95% confidence interval [CI], 0.79 - 0.92) and 83% [95% CI, 0.73 - 0.90], respectively. Area under the curve [AUC] was 0.92. CONCLUSION: VOCs perform very well as non-invasive biomarkers of IBD, with much scope for future improvement and research.

Research activity among physicians in the United Kingdom: results from the Royal College of Physicians Census 2022.

We present the results of the 2022 Census of the Federation of Royal Colleges of Physicians of Edinburgh, Glasgow and London on whether physicians undertake research and the barriers they have encountered. 40% of physicians reported that they undertook research alongside their clinical work. Multivariate analysis of the responses showed that men were 1.6 times more likely to say they undertake research than women. The main barriers to undertaking research were having enough time, organisational factors and a lack of confidence. In this opinion piece we discuss some of the challenges and how they could be addressed.

A Systematic Review and Meta-Analysis: Volatile Organic Compound Analysis in the Detection of Hepatobiliary and Pancreatic Cancers.

BACKGROUND: Hepatobiliary cancers are notoriously difficult to detect, frequently leading to diagnosis in later stages of disease when curative treatment is not an option. The currently used biomarkers such as AFP (alpha-fetoprotein) and CA19.9 lack sensitivity and specificity. Hence, there is an unmet need for an alternative biomarker. AIM: To evaluate the diagnostic accuracy of volatile organic compounds (VOCs) for the detection of hepatobiliary and pancreatic cancers. METHODS: A systematic review of VOCs' use in the detection of hepatobiliary and pancreatic cancers was performed. A meta-analysis was performed using the software R. Heterogeneity was explored through meta-regression analysis. RESULTS: A total of 18 studies looking at 2296 patients were evaluated. Pooled sensitivity and specificity of VOCs for the detection of hepatobiliary and pancreatic cancer were 0.79 (95% CI, 0.72-0.85) and 0.81 (97.5% CI, 0.76-0.85), respectively. The area under the curve was 0.86. Meta-regression analysis showed that the sample media used contributed to heterogeneity. Bile-based VOCs showed the highest precision values, although urine and breath are preferred for their feasibility. CONCLUSIONS: Volatile organic compounds have the potential to be used as an adjunct tool to aid in the early diagnosis of hepatobiliary cancers.

Influence of seasonal and operator variations on diagnostic accuracy of lateral flow devices during the COVID-19 pandemic: a systematic review and meta-analysis.

BACKGROUND: Lateral flow tests (LFT) are point-of-care rapid antigen tests that allow isolation and control of disease outbreaks through convenient, practical testing. However, studies have shown significant variation in their diagnostic accuracy. We conducted a systematic review of the diagnostic accuracy of LFTs for the detection of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) to identify potential factors affecting their performance. METHODS: A systematic search of online databases was carried out to identify studies assessing the sensitivity and specificity of LFTs compared with polymerase chain reaction (PCR) tests. Data were extracted and used to calculate pooled sensitivity and specificity. Meta-regression analysis was conducted to identify covariates influencing diagnostic accuracy. RESULTS: In total, 76 articles with 108,820 test results were identified for analysis. Pooled sensitivity and specificity were 72% (95% confidence interval (CI): 0.68-0.76) and 100% (95% CI: 0.99-1.00), respectively. Staff operation of the LFT showed a statistically significant increase in sensitivity (p=0.04) and specificity (p=0.001) compared with self-operation by the test subjects. The use of LFTs in symptomatic patient subgroups also resulted in higher test sensitivity. CONCLUSION: LFTs display good sensitivity and extremely good specificity for SARS-CoV-2 antigen detection; they become more sensitive in patients with symptoms and when performed by trained professionals.

The Influence of Mechanical Bowel Preparation on Volatile Organic Compounds for the Detection of Gastrointestinal Disease-A Systematic Review.

(1) Background: Colorectal cancer is the second commonest cause of cancer deaths worldwide; recently, volatile organic compounds (VOCs) have been proposed as potential biomarkers of this disease. In this paper, we aim to identify and review the available literature on the influence of mechanical bowel preparation on VOC production and measurement. (2) Methods: A systematic search for studies was carried out for articles relevant to mechanical bowel preparation and its effects on volatile organic compounds. A total of 4 of 1349 papers initially derived from the search were selected. (3) Results: Two studies with a total of 134 patients found no difference in measured breath VOC profiles after bowel preparation; one other study found an increase in breath acetone in 61 patients after bowel preparation, but no other compounds were affected. Finally, the last study showed the alteration of urinary VOC profiles. (4) Conclusions: There is limited data on the effect of bowel preparation on VOC production in the body. As further studies of VOCs are conducted in patients with symptoms of gastrointestinal disease, the quantification of the effect of bowel preparation on their abundance is required.

A Multi-Centre Study to Risk Stratify Colorectal Polyp Surveillance Patients Utilising Volatile Organic Compounds and Faecal Immunochemical Test.

(1) Background: The service capacity for colonoscopy remains constrained, and while efforts are being made to recover elective services, polyp surveillance remains a challenge. (2) Methods: This is a multi-centre study recruiting patients already on polyp surveillance. Stool and urine samples were collected for the faecal immunochemical test (FIT) and volatile organic compounds (VOC) analysis, and all participants then underwent surveillance colonoscopy. (3) Results: The sensitivity and specificity of VOC for the detection of a high-risk finding ((≥2 premalignant polyps including ≥1 advanced polyp or ≥5 premalignant polyps) were 0.94 (95% CI, 0.88 to 0.98) and 0.69 (95% CI, 0.64 to 0.75) respectively. For FIT, the sensitivity was (≥10 µg of haemoglobin (Hb) / g faeces) 0.54 (95% CI, 0.43 to 0.65) and the specificity was 0.79 (95% CI, 0.73 to 0.84). The probability reduction for having a high-risk finding following both negative VOC and FIT will be 24% if both tests are applied sequentially. (4) Conclusion: The diagnostic performance of VOC is superior to FIT for the detection of a high-risk finding. The performance further improves when VOC is applied together with FIT sequentially (VOC first and then FIT). VOC alone or the combination of VOC and FIT can be used as a triage tool for patients awaiting colonoscopy within a polyp surveillance population, especially in resource-constrained healthcare systems.

A systematic review and meta-analysis: the diagnostic accuracy of methylated SEPTIN9 for the detection of hepatocellular carcinoma and the clinical evaluation of its use in combination with other surveillance modalities.

BACKGROUND: Hepatocellular carcinoma (HCC) lacks a suitable biomarker for minimally-invasive disease detection. Methylated SEPTIN9 (mSEPT9) is an emerging liquid biopsy test. We aimed to investigate recent studies that applied mSEPT9 for HCC diagnosis. Furthermore, we evaluated the combinations of other surveillance modalities for the detection of HCC. METHODS: A systematic review was performed on the diagnostic accuracy of mSEPT9 for the detection of HCC. Using a bivariate model, the pooled sensitivity and specificity were calculated. Additionally, Fagan's nomograms were used to calculate the pre-test and post-test probabilities of HCC for various combinations of surveillance modalities. RESULTS: Six full texts were included in the meta-analysis. The pooled sensitivity and specificity of mSEPT9 for the detection of HCC, were 0.80 (95% CI, 0.67-0.89) and 0.90 (95% CI, 0.84-0.94). The area under the receiver operating curve was 0.92. The probability of having HCC for the combinations of mSEPT9+ ultrasound scan (USS) and mSEPT9+ Alpha fetoprotein (AFP) were 0.7% and 1.2% respectively if both tests were negative (in a population with 10% HCC prevalence). The combination of USS and AFP would miss relatively fewer cancers for 1000 patients in comparison to other combinations of two surveillance modalities. CONCLUSION: Test combinations have superior performance for the detection of HCC than any individual test. mSEPT9 has shown promise in the detection of HCC with higher estimates of performance accuracy. mSEPT9 has potential for use as an HCC surveillance modality in adjunct with other tests to improve detection rates. However, cost effectiveness of this approach needs further evaluation.

Implementation of a care bundle improves the management of patients with non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is common and is associated with liver-related and cardiovascular-related morbidity. Our aims were: (1) to review the current management of patients with NAFLD attending hospital clinics in North East England (NEE) and assess the variability in care; (2) develop a NAFLD 'care bundle' to standardise care; (3) to assess the impact of implementation of the NAFLD care bundle. METHODS: A retrospective review was conducted to determine baseline management of patients with NAFLD attending seven hospitals in NEE. A care bundle for the management of NAFLD was developed including important recommendations from international guidelines. Impact of implementation of the bundle was evaluated prospectively in a single centre. RESULTS: Baseline management was assessed in 147 patients attending gastroenterology, hepatology and a specialist NAFLD clinic. Overall, there was significant variability in the lifestyle advice given and management of metabolic risk factors, with patients attending an NAFLD clinic significantly more likely to achieve >10% body weight loss and have metabolic risk factors addressed. Following introduction of the NAFLD bundle 50 patients were evaluated. Use of the bundle was associated with significantly better documentation and implementation of most aspects of patient management including management of metabolic risk factors, documented lifestyle advice and provision of NAFLD-specific patient advice booklets. CONCLUSION: The introduction of an outpatient 'care bundle' led to significant improvements in the assessment and management of patients with NAFLD in the NEE and could help improve and standardise care if used more widely.

Exploring how microbiome signatures change across inflammatory bowel disease conditions and disease locations.

Understanding the variables that influence microbiome studies is critical for successful translational research. Inflammatory bowel disease (IBD) is a complex group of diseases that can present at multiple locations within the Gastrointestinal tract. Here, using the FAMISHED study cohort, we aimed to investigate the relationship between IBD condition, IBD disease location, and the microbiome. Signatures of the microbiome, including measures of diversity, taxonomy, and functionality, all significantly differed across the three different IBD conditions, Crohn's disease (CD), ulcerative colitis (UC), and microscopic colitis (MC). Notably, when stratifying by disease location, patients with CD in the terminal ileum were more similar to healthy controls than patients with CD in the small bowel or colon, however no differences were observed at different disease locations across patients with UC. Change in taxonomic composition resulted in changes in function, with CD at each disease location, UC and MC all having unique functional dysbioses. CD patients in particular had deficiencies in Short-Chain Fatty Acid (SCFA) pathways. Our results demonstrate the complex relationship between IBD and the microbiome and highlight the need for consistent strategies for the stratification of clinical cohorts and downstream analysis to ensure results across microbiome studies and clinical trials are comparable.

Performance of the faecal immunochemical test for the detection of colorectal neoplasms and the role of proton pump inhibitors in their diagnostic accuracy.

AIM: The faecal immunochemical test (FIT) is currently utilized in both symptomatic and screening populations, but little is known about factors that affect its performance. For example, proton pump inhibitor (PPI) therapy has been purported to increase false negative rates. This has significant implications given the extent of PPI prescriptions. The aim of this work was to evaluate the performance of the FIT for the detection of colorectal neoplasms and the impact of PPI therapy on its diagnostic accuracy. METHOD: Symptomatic patients referred on the suspected cancer pathway and those on polyp surveillance between 2015 and 2019 were approached to participate. Estimates of the accuracy of FIT at different cut-off levels in diagnosing colorectal neoplasms were made. Logistic regression was used to assess the effect of PPIs on the FIT results. RESULTS: A total of 667 participants were eligible for the final analysis. At a cut-off of 10 µg/g faeces, the overall sensitivity and specificity of FIT for the detection of colorectal cancer (CRC) was 0.85 (95% CI 0.71-0.94) and 0.81 (95% CI 0.78-0.84), respectively. For the detection of advanced neoplasia, the sensitivity was 0.70 (95% CI 0.58-0.79) and the specificity was 0.83 (95% CI 0.80-0.86). At higher thresholds, the sensitivity steadily declined whilst specificity increased. PPI therapy did not have a significant effect on performance of the FIT. CONCLUSION: FIT is a good rule-out test for the detection of CRC and advanced neoplasia at lower thresholds. PPI therapy does not appear to have an effect on its diagnostic performance.

Systematic review with meta-analysis: volatile organic compound analysis to improve faecal immunochemical testing in the detection of colorectal cancer.

BACKGROUND: Faecal immunochemical test (FIT) is emerging as a valid test to rule-out the presence of colorectal cancer (CRC). However, the accuracy of FIT is dependent on the cut-off applied. An additional low-cost test could improve further detection of CRC. AIMS: To evaluate the efficacy of combined FIT and volatile organic compounds (VOC) in the detection of CRC within symptomatic populations. METHODS: Systematic reviews on the diagnostic accuracy of FIT and VOC, for the detection of CRC, were updated. Meta-analyses were performed adopting a bivariate model for sensitivity and specificity. Clinical utility of combined FIT and VOC was estimated using Fagan's nomogram. Post-test probability of FIT negatives was used as a pre-test probability for VOC. RESULTS: The pooled sensitivity and specificity of FIT at 10 µg/g faeces, for the detection of CRC, were 0.914 (95% confidence interval [CI] = 0.894-0.936) and 0.783 (CI = 0.850-0.696), respectively. For VOC, the sensitivity was 0.837 (CI = 0.781-0.881) and the specificity was 0.803 (CI = 0.870-0.712). The area under the curve for FIT and VOC were 0.926 and 0.885, respectively. In a population with 5% CRC prevalence, the estimated probability of having CRC following a negative FIT was 0.5% and following both negative FIT and VOC was 0.1%. CONCLUSIONS: In a FIT-negative symptomatic population, VOC can be a good test to rule-out the presence of CRC. The estimated probability reduction by 0.4% when both tests being negative offers adequate safety netting in primary care for the exclusion of CRC. The number needed to colonoscope to identify one CRC is eight if either FIT or VOC positive. Cost-effectiveness and clinical accuracy of this approach will need further evaluation.

The impact of pre-operative biologic therapy on post-operative surgical outcomes in ulcerative colitis: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Biologic therapy has emerged as an effective modality amongst the medical treatment options available for ulcerative colitis (UC). However, its impact on post-operative care in patients with UC is still debatable. This review evaluates the risk of post-operative complications following biologic treatment in patients with UC. METHODS: A systematic search of the relevant databases was conducted with the aim of identifying studies that compared the post-operative complication rates of UC patients who were either exposed or not exposed to a biologic therapy prior to their surgery. Outcomes of interest included both infection-related complications and overall surgical morbidity. Pooled odds-ratio (OR) and 95% confidence intervals (CI) were calculated using Review Manager 5.3. RESULTS: In all, 20 studies, reviewing a total of 12,494 patients with UC, were included in the meta-analysis. Of these, 2254 patients were exposed to a biologic therapy prior to surgery. The pooled ORs for infection-related complications (n = 8067) and overall complications (n = 11,869) were 0.98 (95% CI 0.66-1.45) and 1.14 (95% CI 1.04-1.28), respectively, which suggested that there was no significant association between the use of pre-operative biologic therapy and post-operative complications. Interestingly, the interval between the last dose of biologic therapy and surgery did not influence the risk of having a post-operative infection. CONCLUSIONS: This meta-analysis suggests that pre-operative biologic therapy does not increase the overall risk of having post-operative infection-related or other complications. PROSPERO registration id-CRD42019141827.

C-reactive protein and albumin association with mortality of hospitalised SARS-CoV-2 patients: A tertiary hospital experience.

OBJECTIVE: The objective was to study hospitalised COVID-19 patients' mortality and intensive care unit (ICU) admission with covariates of interest (age, gender, ethnicity, clinical presentation, comorbidities and admission laboratory findings). METHODS: Logistic regression analyses were performed for patients admitted to University Hospital, University Hospitals Coventry and Warwickshire NHS Trust, between 24 January 2020 - 13 April 2020. RESULTS: There were 321 patients hospitalised. Median age was 73 years and 189 (59%) were male. Ethnicity was divided between Caucasian (77%), and black, Asian, and minority ethnic (BAME) groups (23%). Commonest symptoms were dyspnoea (62.9%), fever (59.1%) and cough (56%). Gastrointestinal symptoms amounted to 11.8%.Forty-four patients (13.7%) received ICU care. ICU male to female ratio was 3:1 (p=0.027; odds ratio (OR) 2.3; 95% confidence interval (CI) 1.1-4.9), BAME (p=0.008; OR 2.5; 95% CI 1.3-4.9), age >65 years (p=0.026; OR 0.28; 95% CI 0.09-0.93), heart disease (p=0.009; OR 0.2; 95% CI 0.1-0.6) and elevated C-reactive protein (CRP; p<0.001; OR 1.004; 95% CI 1.002-1.008) were associated with ICU admission.One-hundred and four patients (32.4%) died. Age >65 years (p=0.011; OR 5; 95% CI 1.6-21.9), neutrophils (p=0.047), neutrophil:lymphocyte ratio (NLR; p=0.028), CRP (p<0.001) and albumin (p=0.002) were associated with mortality. When analysis adjusted for age, CRP (p<0.001; OR 1.006; 95% CI 1.004-1.008) and albumin (p=0.005; OR 0.94; 95% CI 0.90-0.98) remained associated with mortality. CONCLUSIONS: COVID-19 has high mortality. BAME and male patients were associated with ICU admission. High CRP and low albumin (after correcting for age) were associated with mortality.

Urine as a biological modality for colorectal cancer detection.

Introduction: The increasing incidence of colorectal cancer (CRC) in young adults warrants early and preferably noninvasive diagnostic modalities. Although the current stool-based assays have had good performance indicators for CRC detection, the overall poor uptake remains a challenging issue. However, alternative blood and urine markers are emerging.Areas covered: This paper discusses the various urinary biomarkers available for the detection of CRC. The more commonly encountered drawbacks are the small number of studies and the size of the study population. We discuss the role of microRNA and ProstaglandinE2 in CRC detection. The emergence of new, low-cost technologies, specifically in the detection of volatile organic compounds (VOCs), presents a promising future. We postulate possible mechanisms for the origin of these VOCs in urine and their role in carcinogenesis.Expert opinion: Urinary biomarkers provide an alternative option to the stool-based screening tests. MicroRNA and ProstaglandinE2 have shown utility in CRC detection. Evidence so far suggests that VOCs could also be a potential biomarker for the detection of CRC. In addition to its interaction within the colon lumen, this altered 'VOC signature' might also play a role in carcinogenesis. Low-cost technology may enable such diagnostic methods to be utilized at the point of care.

The role of fecal markers in the investigation of patients with chronic diarrhea.

Chronic diarrhea often presents a dilemma for a practicing clinician as to whether an endoscopic evaluation would be necessary. The current application of colonoscopy-for-most approach increases the burden on the endoscopy services and is associated with higher costs. Therefore, there is a need for newer tools which are cost-effective, less invasive, and easily accessible, in order to triage patients referred for endoscopic evaluation. In this context, fecal markers are becoming considered as triage tools in clinical practice. Emerging evidence in support of their high performance will certainly influence future practice.

Systematic review and meta-analysis: does colonic mural thickening on CT correlate with endoscopic findings at colonoscopy?

BACKGROUND: Colonic mural thickening (MT) is often reported on standard CT examinations of the abdomen and pelvis. It often presents a dilemma for the clinician on whether any further evaluation is needed, especially in the absence of any set guidelines. OBJECTIVE: To evaluate the significance of colonic MT and to assess its correlation with colonoscopy. METHODS: The search strategy was initially developed in Medline and adapted for use in Embase, Medline, NHS Evidence and TRIP. Studies were included if they had reported colonic MT and subsequent colonoscopy in adults. RESULTS: A total of 9 cohort studies examining 1252 patients were selected having undergone both CT and colonoscopy. Of the 1252 patients with MT, 950 had an abnormal colonoscopy. In the presence of MT, the pooled positive predictive value (PPV) of having any abnormal findings at colonoscopy was 0.73 (95% CI 0.60 to 0.84). The pooled PPV for colorectal cancer, in the presence of MT reporting suspicion of cancer, was 0.63 (95% CI 0.49 to 0.75), and MT suggestive of inflammation confirmed at colonoscopy was 0.97. CONCLUSION: The probability of having an abnormal colonoscopy in the presence of MT identified on CT is high, especially for inflammation. Asymptomatic cancers may also be detected; hence, further endoscopic confirmation is reasonable when a finding of MT is demonstrated on CT examinations. Small sample sizes of the available studies and lack of data on the description of MT detected are the main limiting factors in this review. TRIAL REGISTRATION NUMBER: CRD42016039378.

Colonic thickening on computed tomography-does it correlate with endoscopic findings? A protocol for systematic review.

BACKGROUND: Colonic mural thickening is often a finding in standard computed tomography (CT) scans of the abdomen. It often presents clinician with a dilemma on when a further endoscopic evaluation is needed, especially in the absence of guidelines. The aim of this systematic review is to evaluate the significance of bowel wall thickening and to assess its correlation with endoscopy. METHODS: This systematic review will be reported in accordance with the preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. The search strategy will initially be developed in MEDLINE and adapted for use in EMBASE, MEDLINE, NHS evidence and TRIP. Two reviewers will independently conduct a study selection, data extraction and risk of bias assessment for the screened studies. Data synthesis will be conducted using Review Manager software 5.3. The outcome of any dichotomous data will be presented as relative risk with confidence intervals. DISCUSSION: It is extremely useful for the practising clinician to know which patients need further endoscopic evaluation. Even though there are several studies on this issue, none of them have attempted to produce a systematic review. We hope this systematic review will provide a substantiate evidence for future clinical practice. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016039378.