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 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.

Utility of volatile organic compounds as a diagnostic tool in preterm infants.

BACKGROUND: Volatile organic compounds (VOCs) are hydrocarbons that originate within different healthy and diseased tissues. VOCs can be secreted into the circulation and then excreted in the urine and faeces. In the lungs, VOCs are locally produced and can be detected in exhaled breath. VOCs can be identified using non-invasive techniques, which make their use in preterm infants safe and desirable. METHODS: A systematic search of the literature in PubMed, Embase and Web of Science was conducted looking for VOCs techniques and diagnostic performance in preterm infants. A total of 50 articles identified with only seven papers were included in the final analysis in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). RESULTS: VOCs could diagnose necrotising enterocolitis up to 4 days before a clinical diagnosis; for late onset sepsis, up to 3 days before; and for bronchopulmonary dysplasia, up to 2 weeks before. In addition to these diagnostic uses, VOCs analysis could also distinguish breastfed from formula-fed preterm neonates in the first month of life. CONCLUSION: VOCs analysis is a non-invasive tool that makes the use in preterm infants of preference. VOCs analytic techniques require more research and consensus between researchers to overcome their limitations. IMPACT: Volatile organic compounds are hydrocarbons that can separate between healthy and diseased states in preterm infants. Biomarker panels developed from volatile organic compounds are potential diagnostic tools. The non-invasive nature of acquiring volatile organic compounds markers make it desirable in the paediatric patients. Research into exact chemical components of the volatile organic compounds can inform about the pathophysiology of disease in preterm infants. More robust longitudinal studies with repeated experiments are required before volatile organic compounds can be applied in clinical practice.

Non-Invasive Detection and Staging of Colorectal Cancer Using a Portable Electronic Nose.

Electronic noses (e-nose) offer potential for the detection of cancer in its early stages. The ability to analyse samples in real time, at a low cost, applying easy-to-use and portable equipment, gives e-noses advantages over other technologies, such as Gas Chromatography-Mass Spectrometry (GC-MS). For diseases such as cancer with a high mortality, a technology that can provide fast results for use in routine clinical applications is important. Colorectal cancer (CRC) is among the highest occurring cancers and has high mortality rates, if diagnosed late. In our study, we investigated the use of portable electronic nose (PEN3), with further analysis using GC-TOF-MS, for the analysis of gases and volatile organic compounds (VOCs) to profile the urinary metabolome of colorectal cancer. We also compared the different cancer stages with non-cancers using the PEN3 and GC-TOF-MS. Results obtained from PEN3, and GC-TOF-MS demonstrated high accuracy for the separation of CRC and non-cancer. PEN3 separated CRC from non-cancerous group with 0.81 AUC (Area Under the Curve). We used data from GC-TOF-MS to obtain a VOC profile for CRC, which identified 23 potential biomarker VOCs for CRC. Thus, the PEN3 and GC-TOF-MS were found to successfully separate the cancer group from the non-cancer group.

Exploratory Study Using Urinary Volatile Organic Compounds for the Detection of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) biomarkers are lacking in clinical practice. We therefore explored the pattern and composition of urinary volatile organic compounds (VOCs) in HCC patients. This was done in order to assess the feasibility of a potential non-invasive test for HCC, and to enhance our understanding of the disease. This pilot study recruited 58 participants, of whom 20 were HCC cases and 38 were non-HCC cases. The non-HCC cases included healthy individuals and patients with various stages of non-alcoholic fatty liver disease (NAFLD), including those with and without fibrosis. Urine was analysed using gas chromatography-ion mobility spectrometry (GC-IMS) and gas chromatography-time-of-flight mass spectrometry (GC-TOF-MS). GC-IMS was able to separate HCC from fibrotic cases with an area under the curve (AUC) of 0.97 (0.91-1.00), and from non-fibrotic cases with an AUC of 0.62 (0.48-0.76). For GC-TOF-MS, a subset of samples was analysed in which seven chemicals were identified and tentatively linked with HCC. These include 4-methyl-2,4-bis(p-hydroxyphenyl)pent-1-ene (2TMS derivative), 2-butanone, 2-hexanone, benzene, 1-ethyl-2-methyl-, 3-butene-1,2-diol, 1-(2-furanyl)-, bicyclo(4.1.0)heptane, 3,7,7-trimethyl-, [1S-(1a,3ß,6a)]-, and sulpiride. Urinary VOC analysis using both GC-IMS and GC-TOF-MS proved to be a feasible method of identifying HCC cases, and was also able to enhance our understanding of HCC pathogenesis.

Role of methylated septin 9 as an adjunct diagnostic and prognostic biomarker in hepatocellular carcinoma.

BACKGROUND: Methylated septin 9 (mSEPT9) has a role in hepatocarcinogenesis. We evaluated mSEPT9 performance in patients with hepatocellular carcinoma (HCC) and those at risk of HCC METHODS: Using Epi-proColon® V2.0 assay adapted for 1 mL plasma, we investigated mSEPT9 sensitivity, specificity, associations with influential covariates and relation to death. RESULTS: Of 141 participants included, 136 had liver disease, 38 with HCC (mean-age 71 years) and 103 without HCC (mean-age 56.8 years), with further five without liver disease. 41 patients died (23 HCC) by the end of the study follow-up period. In HCC, mSEPT9 sensitivity and specificity were 89.47% (CI:75.20%-97.06%) and 81.55% (CI:72.70%-88.51%), whilst alpha fetoprotein (AFP) sensitivity and specificity were 50% (CI:33.38%-66.62%) and 97.09% (CI:91.72%-99.40%), respectively. Age-adjusted logistic regression showed mSEPT9 was associated with age, body mass index, HCC, liver cirrhosis, AFP, platelets, neutrophil-to-lymphocyte-ratio, albumin-bilirubin grade and fibrosis-4 index (p < 0.05). Odds for HCC patients to have positive mSEPT9 were 27.4 times more than those without HCC. Time-to-death was associated with mSEPT9 positivity (p < 0.05). Kaplan-Meier curves showed higher HCC survival with mSEPT9 compared to AFP. CONCLUSIONS: The mSEPT9 offers potential diagnostic and prognostic biomarker for HCC. After adjusting for age, mSEPT9 remained associated with liver function, liver fibrosis and inflammatory surrogate markers.

Recent treatment advances and practical management of hepatitis D virus.

Hepatitis D virus (HDV), also referred to as hepatitis delta virus, is the smallest virus capable of causing human disease. It is unable to replicate on its own and can only propagate in the presence of hepatitis B virus (HBV). Infection with both HBV and HDV frequently results in more severe disease than HBV alone, with higher instances of cirrhosis, liver failure and hepatocellular carcinoma (HCC). Thus, there is a need for effective treatment for HDV; however, currently approved treatment options are very limited both in terms of their efficacy and availability. This makes the management of HDV a challenge for physicians. In this review, we look at the background, diagnosis and treatment of HDV, informed by our hospital data, to set out the optimal management of HDV; we also explore novel treatment options for this disease.

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 Fatty Liver, Cirrhosis, and Liver Cancer Study (TENDENCY): Protocol for a Multicenter Case-Control Study.

BACKGROUND: Hepatocellular cancer (HCC) is associated with high mortality, and early diagnosis leads to better survival. Patients with cirrhosis, especially due to nonalcoholic fatty liver disease and viral hepatitis, are at higher risk of developing HCC and form the main screening group. The current screening methods for HCC (6-monthly screening with serum alpha fetoprotein and ultrasound liver) have low sensitivity; hence, there is a need for better screening markers for HCC. OBJECTIVE: Our study, TENDENCY, aims to validate the novel screening markers (methylated septin 9, urinary volatile organic compounds, and urinary peptides) for HCC diagnosis and study these noninvasive biomarkers in liver disease. METHODS: This is a multicenter, nested case-control study, which involves comparing the plasma levels of methylated septin 9 between confirmed HCC cases and patients with cirrhosis (control group). It also includes the comparison of urine samples for the detection of HCC-specific volatile organic compounds and peptides. Based on the findings of a pilot study carried out at University Hospital Coventry & Warwickshire, we estimated our sample size to be 308 (n=88, 29% patients with HCC; n=220, 71% patients with cirrhosis). Urine and plasma samples will be collected from all participants and will be frozen at -80 °C until the end of recruitment. Gas chromatography-mass spectrometry will be used for urinary volatile organic compounds detection, and capillary electrophoresis-mass spectrometry will be used for urinary peptide identification. Real-time polymerase chain reaction will be used for the qualitative detection of plasma methylated septin 9. The study will be monitored by the Research and Development department at University Hospital Coventry & Warwickshire. RESULTS: The recruitment stage was completed in March 2023. The TENDENCY study is currently in the analysis stage, which is expected to finish by November 2023. CONCLUSIONS: There is lack of effective screening tests for hepatocellular cancer despite higher mortality rates. The application of more sensitive plasma and urinary biomarkers for hepatocellular cancer screening in clinical practice will allow us to detect the disease at earlier stages and hence, overall, improve HCC outcomes. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/44264.

Urinary Volatiles and Chemical Characterisation for the Non-Invasive Detection of Prostate and Bladder Cancers.

Bladder cancer (BCa) and prostate cancer (PCa) are some of the most common cancers in the world. In both BCa and PCa, the diagnosis is often confirmed with an invasive technique that carries a risk to the patient. Consequently, a non-invasive diagnostic approach would be medically desirable and beneficial to the patient. The use of volatile organic compounds (VOCs) for disease diagnosis, including cancer, is a promising research area that could support the diagnosis process. In this study, we investigated the urinary VOC profiles in BCa, PCa patients and non-cancerous controls by using gas chromatography-ion mobility spectrometry (GC-IMS) and gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) to analyse patient samples. GC-IMS separated BCa from PCa (area under the curve: AUC: 0.97 (0.93-1.00)), BCa vs. non-cancerous (AUC: 0.95 (0.90-0.99)) and PCa vs. non-cancerous (AUC: 0.89 (0.83-0.94)) whereas GC-TOF-MS differentiated BCa from PCa (AUC: 0.84 (0.73-0.93)), BCa vs. non-cancerous (AUC: 0.81 (0.70-0.90)) and PCa vs. non-cancerous (AUC: 0.94 (0.90-0.97)). According to our study, a total of 34 biomarkers were found using GC-TOF-MS data, of which 13 VOCs were associated with BCa, seven were associated with PCa, and 14 VOCs were found in the comparison of BCa and PCa.

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.

Pathophysiological Implications of Urinary Peptides in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is known to be associated with protein alterations and extracellular fibrous deposition. We investigated the urinary proteomic profiles of HCC patients in this prospective cross sectional multicentre study. 195 patients were recruited from the UK (Coventry) and Germany (Hannover) between 1 January 2013 and 30 June 2019. Out of these, 57 were HCC patients with a background of liver cirrhosis (LC) and 138 were non-HCC controls; 72 patients with LC, 57 with non-cirrhotic liver disease and 9 with normal liver function. Analysis of the urine samples was performed by capillary electrophoresis (CE) coupled to mass spectrometry (MS). Peptide sequences were obtained and 31 specific peptide markers for HCC were identified and further integrated into a multivariate classification model. The peptide model demonstrated 79.5% sensitivity and 85.1% specificity (95% CI: 0.81-0.93, p < 0.0001) for HCC and 4.1-fold increased risk of death (95% CI: 1.7-9.8, p = 0.0005). Proteases potentially involved in HCC progression were mapped to the N- and C-terminal sequence motifs of the CE-MS peptide markers. In silico protease prediction revealed that kallikrein-6 (KLK6) elicits increased activity, whilst Meprin A subunit α (MEP1A) has reduced activity in HCC compared to the controls. Tissue expression of KLK6 and MEP1A was subsequently verified by immunohistochemistry.

Neutrophil to lymphocyte ratio and albumin bilirubin grade in hepatocellular carcinoma: A systematic review.

BACKGROUND: Hepatocellular carcinoma (HCC) is a frequent cause of cancer related death globally. Neutrophil to lymphocyte ratio (NLR) and albumin bilirubin (ALBI) grade are emerging prognostic indicators in HCC. AIM: To study published literature of NLR and ALBI over the last five years, and to validate NLR and ALBI locally in our centre as indicators of HCC survival. METHODS: A systematic review of the published literature on PubMed of NLR and ALBI in HCC over the last five years. The search followed the guidelines of the preferred reporting items for systematic reviews and meta-analyses. Additionally, we also investigated HCC cases between December 2013 and December 2018 in our centre. RESULTS: There were 54 studies describing the relation between HCC and NLR and 95 studies describing the relation between HCC and ALBI grade over the last five years. Our local cohort of patients showed NLR to have a significant negative relationship to survival (P = 0.011). There was also significant inverse relationship between the size of the largest HCC nodule and survival (P = 0.009). Median survival with alpha fetoprotein (AFP) < 10 KU/L was 20 mo and with AFP > 10 KU/L was 5 mo. We found that AFP was inversely related to survival, this relationship was not statically significant (P = 0.132). Mean survival for ALBI grade 1 was 37.7 mo, ALBI grade 2 was 13.4 months and ALBI grade 3 was 4.5 mo. ALBI grades performed better than Child Turcotte Pugh score in detecting death from HCC. CONCLUSION: NLR and ALBI grade in HCC predict survival better than the conventional alpha fetoprotein. ALBI grade performs better than Child Turcotte Pugh score. These markers are done as part of routine clinical care and in cases of normal alpha fetoprotein, these markers could give a better understanding of the patient disease progression. NLR and ALBI grade could have a role in modified easier to learn staging and prognostic systems for HCC.

Differentiating cancer types using a urine test for volatile organic compounds.

BACKGROUND: In the human body, volatile organic compounds (VOCs) are produced by different tissues then secreted in different body fluids and subsequently excreted. Here we explore a non-invasive method for the detection of liver, prostate and bladder cancers. METHODS: We recruited 140 cases. There were 31 hepatocellular carcinomas (HCC), 62 prostate carcinomas, 29 bladder carcinomas and 18 non-cancer cases. Male to female ratio was 5:1 and mean age was 72 years. Urinary VOCs were detected by applying solid-phase microextraction (SPME) technique. RESULTS: The sensitivity for detection of HCC with normal alpha fetoprotein (AFP) was 68% (SE 0.06, 95% CI 0.54 to 0.81 and P < 0.005). The VOCs sensitivity in the detection of HCC cases with raised AFP was 83%. (SE 0.05, 95% CI 0.73 to 0.93 and P < 0.0001). The VOCs sensitivity for prostate cancer detection was 70% (SE 0.049, 95% CI 0.60 to 0.79 and P < 0.0002) and sensitivity for bladder cancer detection was 81% (SE 0.052, 95% CI 0.70 to 0.91 and P < 0.0001). CONCLUSIONS: SPME urinary VOCs analysis was able to differentiate between controls and each of hepatocellular, prostate and bladder cancers. This suggests that urinary VOCs are cancer specific and could potentially be used as a diagnostic method.

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.

Discovery, validation and sequencing of urinary peptides for diagnosis of liver fibrosis-A multicentre study.

BACKGROUND: Liver fibrosis is a consequence of chronic inflammation and is associated with protein changes within the hepatocytes structure. In this study, we aimed to investigate if this is reflected by the urinary proteome and can be explored to diagnose liver fibrosis in patients with chronic liver disease. METHODS: In a multicentre combined cross-sectional and prospective diagnostic test validation study, 129 patients with varying degrees of liver fibrosis and 223 controls without liver fibrosis were recruited. Additionally, 41 patients with no liver, but kidney fibrosis were included to evaluate interference with expressions of kidney fibrosis. Urinary low molecular weight proteome was analysed by capillary electrophoresis coupled to mass spectrometry (CE-MS) and a support vector machine marker model was established by integration of peptide markers for liver fibrosis. FINDINGS: CE-MS enabled identification of 50 urinary peptides associated with liver fibrosis. When combined into a classifier, LivFib-50, it separated patients with liver fibrosis (N = 31) from non-liver disease controls (N = 123) in cross-sectional diagnostic phase II evaluation with an area under the curve (AUC) of 0.94 (95% confidence intervals (CI): 0.89-0.97, p<0.0001). When adjusted for age, LivFib-50 demonstrated an AUC of 0.94 (95% CI: 0.89-0.97, p<0.0001) in chronic liver disease patients with (N = 19) or without (N = 17) liver fibrosis progression. In this prospective diagnostic phase III validation set, age-adjusted LivFib-50 showed 84.2% sensitivity (95% CI: 60.4-96.6) and 82.4% specificity (95% CI: 56.6-96.2) for detection of liver fibrosis. The sequence-identified peptides are mainly fragments of collagen chains, uromodulin and Na/K-transporting ATPase subunit γ. We also identified ten putative proteolytic cleavage sites, eight were specific for matrix metallopeptidases and two for cathepsins. INTERPRETATION: In liver fibrosis, urinary peptides profiling offers potential diagnostic markers and leads to discovery of proteolytic sites that could be targets for developing anti-fibrotic therapy.

Diagnosing Inflammatory bowel disease using noninvasive applications of volatile organic compounds: a systematic review.

Introduction: Inflammatory bowel disease (IBD) is a common disease with significant morbidity. Noninvasive diagnostic techniques are lacking in IBD. Currently, fecal calprotectin is a sensitive marker of gut inflammation however is not specific to Crohn's disease (CD) or ulcerative colitis (UC) alone. Volatile organic compounds (VOCs) were shown to have potential in IBD diagnosis.Areas covered: This systematic review aimed to examine the next-generation diagnosis of IBD in adults and children using VOCs. An in-depth literature-based search of current clinical studies of VOCs in the diagnosis of IBD was undertaken. Accuracy of IBD detection varied according to the technologies applied. Breath VOCs studies were pooled giving an overall sensitivity of 85% (95%CI: 79-89%) and specificity of 79% (95%CI 73-84%) whilst pooled fecal VOCs studies revealed a sensitivity of 87% (95%CI 77-93%) and specificity of 91% (95%CI 82-96%). Studies were limited by the variance of techniques applied in VOCs detection and the absence of well-designed longitudinal studies.Expert opinion: VOCs can be consistently and effectively detected in urine, breath, and stool in IBD patients. The sensitivity of breath VOCs in detecting IBD was comparable to feces. However, optimal VOCs detection methodology and biological sampling still need to be standardized..

Small Intrahepatic Vein Budd-Chiari Syndrome Complicated by Fusobacterium nucleatum Peritonitis.

Budd-Chiari syndrome is a rare disorder with significant liver-related complications. We present a 28-year-old woman with a 1-month history of weight loss and ascites. Hepatic venogram showed patent hepatic veins and inferior vena cava; however, there was an increased hepatic venous pressure gradient, which is clinically significant for portal hypertension. Hereditary and acquired thrombophilia workup was unrevealing. During admission, she developed peritonitis with Fusobacterium nucleatum and was treated with piperacillin-tazobactam. Liver biopsy showed vascular changes with features of venous outflow obstruction, and she was diagnosed with "small hepatic vein" Budd-Chiari syndrome. She was treated with transjugular intrahepatic portosystemic stent-shunt and tinzaparin, with significant clinical improvement.