Efficacy and Safety of Ustekinumab for Ulcerative Colitis Through 4 Years: Final Results of the UNIFI Long-Term Maintenance Study.

INTRODUCTION: Ulcerative colitis (UC) is a chronic condition that may require long-term treatment. We report the final efficacy and safety results of the UNIFI long-term extension study of ustekinumab in patients with UC through 4 years. METHODS: Ustekinumab induction responders who completed 44 weeks of maintenance treatment and agreed to enter the long-term extension continued their subcutaneous maintenance therapy (90 mg ustekinumab every 8 or 12 weeks [q8w or q12w] or placebo). Starting at week 56, randomized patients could receive dose adjustment to 90 mg q8w. Symptoms and adverse events were assessed through the study; endoscopic assessment was conducted at week 200. RESULTS: Of the 348 patients randomized to subcutaneous ustekinumab at maintenance baseline (q8w and q12w combined), 55.2% were in symptomatic remission at week 200. A greater proportion of biologic-naive patients (67.2% [117/174]) were in symptomatic remission than those with a history of biologic failure (41.6% [67/161]). Among patients in symptomatic remission at week 200, 96.4% were corticosteroid-free. Of the 171 patients with endoscopic evaluation at week 200, 81.6% (71/87) in the q12w group and 79.8% (67/84) in the q8w group had endoscopic improvement. From weeks 156 to the final safety visit (up to week 220), no deaths, major adverse cardiovascular events, or tuberculosis occurred in patients receiving ustekinumab. Nasopharyngitis, UC worsening, and upper respiratory tract infections were the most frequently reported adverse events. DISCUSSION: The long-term efficacy of ustekinumab maintenance in patients with UC was confirmed through 4 years. No new safety signals were observed. ClinicalTrials.gov number NCT02407236.

Impact of Suaahara, an at-scale multisectoral nutrition programme, on health workers' maternal and child health, and nutrition knowledge and skills in Nepal.

Suaahara, an at-scale multisectoral nutrition programme in Nepal, aimed to advance knowledge and skills of frontline health workers to improve the quality of nutrition and health services at health facility and community levels. This study assessed the impact of Suaahara interventions on knowledge and skills of health facility workers and Female Community Health Volunteers (FCHVs). The study used a quasi-experimental design in which four Suaahara intervention districts were compared with pair-matched comparison districts. One health facility worker and three FCHVs from each survey cluster were included. Baseline survey consisted of 93 health facility workers (2015) and 118 FCHVs (2012), and endline survey (2022) consisted of 40 health facility workers and 120 FCHVs. Difference-in-differences regression models employing intent-to-treat analysis, accounting for clustering at the district level, assessed the impact of intervention. The intervention, relative to comparison, had no effect on health facility workers' knowledge. There was a positive effect, however, on FCHVs' knowledge in intervention relative to comparison areas on exclusive breastfeeding, timing of introduction of complementary feeding, sick child feeding and growth monitoring and promotion (GMP) for children under 2 years. Health facility workers and FCHVs in intervention versus comparison districts had higher endline scores for skills related to measuring the weight of children and pregnant women, measuring the height/length of children, conducting GMP for children under 2 years and identifying malnourished children. Suaahara interventions improved the capacity of health workers, particularly nutrition-related knowledge among FCHVs and GMP-related skills of both health facility workers and FCHVs.

Impact of Suaahara, an integrated nutrition programme, on maternal and child nutrition at scale in Nepal.

Suaahara was an innovative, complex, multi-sectoral, large-scale, nutrition programme in Nepal to increase exposure to nutrition-related information and services, improve nutrition-related knowledge and practices among pregnant women and mothers of infants and young children, and improve their nutrition. This study evaluated the effectiveness of Suaahara to improve nutrition and nutrition-related practices by comparing changes over 10 years between intervention and comparison districts. The samples of households at baseline in 2012 and endline in 2022 were 2040 and 2480, respectively, from 120 old wards. The impact was estimated using intent-to-treat regression models in which survey year, arm and their interaction were fixed effects, accounting for district clustering, with the interaction estimating differences between arms in changes over time. The intervention, relative to comparison, reduced maternal underweight by 8.43 percentage points (p < 0.001), consistent with improved maternal and fetal condition that was manifested as the greater length of 0.761 z-scores (p = 0.004) of infants 0-5.9 months. Complementary feeding practices with children between 6 and 23.9 months of age improved more in the intervention than comparison districts: child dietary diversity by 0.294 food groups (p = 0.072) and minimum dietary diversity by 9.51 percentage points (p = 0.028), feeding sick child more (p = 0.002) and administering oral rehydration solution and zinc for diarrhoea (p = 0.057) by about 17 percentage points each, and minimum meal frequency (p = 0.004) and minimum acceptable diet (p = 0.022) by about 15 percentage points each. Substantial impacts were demonstrated despite political restructuring, earthquakes, and other major challenges that Nepal and Suaahara faced and limitations in statistical power because of the reduced number of districts that then could be included in the study. Registered at clinicaltrials.gov with identifier NCT05448287.

Au-courant and novel technologies for efficient doubled haploid development in barley (Hordeum vulgare L.).

Bounteous modern and innovative biotechnological tools have resulted in progressive development in the barley breeding program. Doubled haploids developed (homozygous lines) in a single generation is significant. Since the first discovery of haploid plants in 1920 and, in particular, after discovering in vitro androgenesis in 1964 by Guha and Maheshwari, the doubled haploidy techniques have been progressively developed and constantly improved. It has shortened the cultivar development time and has been extensively used in: genetic studies, gene mapping, marker/trait association, and QTL studies. In barley, the haploid occurrence developed gradually from being a sporadic and random process (spontaneous) to haploid development by in vivo method of modified pollination or by in vitro culture of immature male or female gametophytes. Although significant improvement in DH induction protocols has been made, challenges still exist for improvement in areas such as: low efficiency, albinism, genotypic specificity etc. Here, the paper focuses on: haploidization via different in vitro, in vivo techniques, the recent advances technologies like centromere-mediated haploidization, hap induction gene, and Doubled haploid CRISPR. The au-courant work of different researchers in barley using these technologies is reviewed. Studies on different factors affecting haploid induction and work on genome doubling of barley haploids to produce DH lines via spontaneous and induced technologies has also been highlighted.

IL-4 Treatment Mitigates Experimental Cerebral Malaria by Reducing Parasitemia, Dampening Inflammation, and Lessening the Cytotoxicity of T Cells.

Cytokine responses to malaria play important roles in both protective immunity development and pathogenesis. Although the roles of cytokines such as TNF-α, IL-12, IFN-γ, and IL-10 in immunity and pathogenesis to the blood stage malaria are largely known, the role of IL-4 remains less understood. IL-4 targets many cell types and induces multiple effects, including cell proliferation, gene expression, protection from apoptosis, and immune regulation. Accordingly, IL-4 has been exploited as a therapeutic for several inflammatory diseases. Malaria caused by Plasmodium falciparum manifests in many organ-specific fatal pathologies, including cerebral malaria (CM), driven by a high parasite load, leading to parasite sequestration in organs and consequent excessive inflammatory responses and endothelial damage. We investigated the therapeutic potential of IL-4 against fatal malaria in Plasmodium berghei ANKA-infected C57BL/6J mice, an experimental CM model. IL-4 treatment significantly reduced parasitemia, CM pathology, and mortality. The therapeutic effect of IL-4 is mediated through multiple mechanisms, including enhanced parasite clearance mediated by upregulation of phagocytic receptors and increased IgM production, and decreased brain inflammatory responses, including reduced chemokine (CXCL10) production, reduced chemokine receptor (CXCR3) and adhesion molecule (LFA-1) expression by T cells, and downregulation of cytotoxic T cell lytic potential. IL-4 treatment markedly reduced the infiltration of CD8+ T cells and brain pathology. STAT6, PI3K-Akt-NF-κB, and Src signaling mediated the cellular and molecular events that contributed to the IL-4-dependent decrease in parasitemia. Overall, our results provide mechanistic insights into how IL-4 treatment mitigates experimental CM and have implications in developing treatment strategies for organ-specific fatal malaria.

Study of capsule endoscopy delivery at scale through enhanced artificial intelligence-enabled analysis (the CESCAIL study).

AIM: Lower gastrointestinal (GI) diagnostics have been facing relentless capacity constraints for many years, even before the COVID-19 era. Restrictions from the COVID pandemic have resulted in a significant backlog in lower GI diagnostics. Given recent developments in deep neural networks (DNNs) and the application of artificial intelligence (AI) in endoscopy, automating capsule video analysis is now within reach. Comparable to the efficiency and accuracy of AI applications in small bowel capsule endoscopy, AI in colon capsule analysis will also improve the efficiency of video reading and address the relentless demand on lower GI services. The aim of the CESCAIL study is to determine the feasibility, accuracy and productivity of AI-enabled analysis tools (AiSPEED) for polyp detection compared with the 'gold standard': a conventional care pathway with clinician analysis. METHOD: This multi-centre, diagnostic accuracy study aims to recruit 674 participants retrospectively and prospectively from centres conducting colon capsule endoscopy (CCE) as part of their standard care pathway. After the study participants have undergone CCE, the colon capsule videos will be uploaded onto two different pathways: AI-enabled video analysis and the gold standard conventional clinician analysis pathway. The reports generated from both pathways will be compared for accuracy (sensitivity and specificity). The reading time can only be compared in the prospective cohort. In addition to validating the AI tool, this study will also provide observational data concerning its use to assess the pathway execution in real-world performance. RESULTS: The study is currently recruiting participants at multiple centres within the United Kingdom and is at the stage of collecting data. CONCLUSION: This standard diagnostic accuracy study carries no additional risk to patients as it does not affect the standard care pathway, and hence patient care remains unaffected.

Contextual Cluster-Based Glow-Worm Swarm Optimization (GSO) Coupled Wireless Sensor Networks for Smart Cities.

The cluster technique involves the creation of clusters and the selection of a cluster head (CH), which connects sensor nodes, known as cluster members (CM), to the CH. The CH receives data from the CM and collects data from sensor nodes, removing unnecessary data to conserve energy. It compresses the data and transmits them to base stations through multi-hop to reduce network load. Since CMs only communicate with their CH and have a limited range, they avoid redundant information. However, the CH's routing, compression, and aggregation functions consume power quickly compared to other protocols, like TPGF, LQEAR, MPRM, and P-LQCLR. To address energy usage in wireless sensor networks (WSNs), heterogeneous high-power nodes (HPN) are used to balance energy consumption. CHs close to the base station require effective algorithms for improvement. The cluster-based glow-worm optimization technique utilizes random clustering, distributed cluster leader selection, and link-based routing. The cluster head routes data to the next group leader, balancing energy utilization in the WSN. This algorithm reduces energy consumption through multi-hop communication, cluster construction, and cluster head election. The glow-worm optimization technique allows for faster convergence and improved multi-parameter selection. By combining these methods, a new routing scheme is proposed to extend the network's lifetime and balance energy in various environments. However, the proposed model consumes more energy than TPGF, and other protocols for packets with 0 or 1 retransmission count in a 260-node network. This is mainly due to the short INFO packets during the neighbor discovery period and the increased hop count of the proposed derived pathways. Herein, simulations are conducted to evaluate the technique's throughput and energy efficiency.

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.

Randomized Trial of Metformin With Anti-Tuberculosis Drugs for Early Sputum Conversion in Adults With Pulmonary Tuberculosis.

BACKGROUND: Metformin, by reducing intracellular Mycobacterium tuberculosis growth, can be considered an adjunctive therapy to anti-tuberculosis treatment (ATT). We determined whether metformin with standard ATT reduces time to sputum culture conversion and tissue inflammation in adults with pulmonary tuberculosis (PTB). METHODS: In a randomized, 8-week, clinical trial, newly diagnosed, culture-positive PTB patients were randomized to standard ATT (HREZ = control arm) or standard ATT plus daily 1000 mg metformin (MET-HREZ = Metformin with Rifampicin [METRIF] arm) for 8 weeks during 2018-2020 at 5 sites in India. The primary end point was time to sputum culture conversion by liquid culture during 8 weeks of ATT. Plasma inflammatory markers were estimated in a subset. A Cox proportional hazard model was used to estimate time and predictors of culture conversion. RESULTS: Of the 322 patients randomized, 239 (74%) were male, and 212 (66%) had bilateral disease on chest radiograph with 54 (18%) showing cavitation. The median time to sputum culture conversion by liquid culture was 42 days in the METRIF arm and 41 days in the control arm (hazard ratio, 0.8; 95% confidence interval [CI], .624-1.019). After 8 weeks of ATT, cavitary lesions on X-ray (7, 5.3% vs 18, 12.9%; relative risk, 0.42; 95% CI, .18-.96; P = .041) and inflammatory markers were significantly lower in the METRIF arm. Higher body mass index and lower sputum smear grading were associated with faster sputum culture conversion. CONCLUSIONS: The addition of metformin to standard ATT did not hasten sputum culture conversion but diminished excess inflammation, thus reducing lung tissue damage as seen by faster clearance on X-ray and reduced inflammatory markers. CLINICAL TRIALS REGISTRATION: Clinical Trial Registry of India (CTRI/2018/01/011176).

Early Symptomatic Improvement After Ustekinumab Therapy in Patients With Ulcerative Colitis: 16-Week Data From the UNIFI Trial.

BACKGROUND & AIMS: Rapid symptomatic relief is an important treatment goal for patients with ulcerative colitis (UC). We aimed to characterize early response with ustekinumab in patients with moderate-to-severe UC during the initial 16 weeks of treatment. METHODS: We performed a post hoc analysis of data from A Study to Evaluate the Safety and Efficacy of Ustekinumab Induction and Maintenance Therapy in Participants With Moderately to Severely Active Ulcerative Colitis trial. Patients (N = 961) were randomized (1:1:1) to receive intravenous 130 mg ustekinumab, approximately 6 mg/kg ustekinumab, or placebo at week 0. Symptomatic remission, absolute stool number, Mayo stool frequency and rectal bleeding subscores, partial Mayo score, C-reactive protein, and fecal calprotectin were assessed in the overall population and for patients in the biologic-naïve or prior biologic failure subgroups. RESULTS: A significantly greater percentage of patients in the 130-mg ustekinumab (20.0%; P = .015) or approximately 6-mg/kg ustekinumab (20.2%; P = .012) groups achieved symptomatic remission at week 2 vs placebo (12.9%). Mean [SD] changes from baseline in daily stool number on day 7 were greater in the ustekinumab groups (-1.1 [2.6] in 130 mg [P = .065] and -1.2 [2.5] in ∼6 mg/kg [P = .017]) vs placebo (-0.7 [2.7]). The percentage of patients with Mayo stool frequency subscore of 1 or less and rectal bleeding subscore of 0 increased from baseline through week 16 for both ustekinumab groups. Significant improvements in partial Mayo scores were observed by week 2 in both ustekinumab groups vs placebo (P ≤ .001). Significantly more patients in the ustekinumab groups had normalized C-reactive protein levels from week 2 to week 8 vs placebo (P ≤ .05). Similar results were observed with normalized fecal calprotectin levels between week 2 and week 4 (P ≤ .05). CONCLUSIONS: Ustekinumab improved symptoms in patients with UC compared with placebo in as early as 7 days, indicating rapid onset of effect after induction. CLINICAL TRIAL REGISTRY NUMBER: ClinicalTrials.gov: NCT02407236.

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.

Minimal Gluten Exposure Alters Urinary Volatile Organic Compounds in Stable Coeliac Disease.

Coeliac disease (CD) patients are distinguishable from healthy individuals via urinary volatile organic compounds (VOCs) analysis. We exposed 20 stable CD patients on gluten-free diet (GFDs) to a 14-day, 3 g/day gluten challenge (GCh), and assessed urinary VOC changes. A control cohort of 20 patients continued on GFD. Urine samples from Days 0, 7, 14, 28 and 56 were analysed using Lonestar FAIMS and Markes Gas Chromatography-Time of Flight-Mass Spectrometer (GC-TOF-MS). VOC signatures on D (day) 7-56 were compared with D0. Statistical analysis was performed using R. In GCh patients, FAIMS revealed significant VOC differences for all time points compared to D0. GC-TOF-MS revealed significant changes at D7 and D14 only. In control samples, FAIMS revealed significant differences at D7 only. GC-TOF-MS detected no significant differences. Chemical analysis via GC-MS-TOF revealed 12 chemicals with significantly altered intensities at D7 vs. D0 for GCh patients. The alterations persisted for six chemicals at D14 and one (N-methyltaurine) remained altered after D14. This low-dose, short-duration challenge was well tolerated. FAIMS and GC-TOF-MS detected VOC signature changes in CD patients when undergoing a minimal GCh. These findings suggest urinary VOCs could have a role in monitoring dietary compliance in CD patients.

Malnutrition matters: Association of stunting and underweight with early childhood development indicators in Nepal.

Malnutrition is a threat to optimal child development, with its occurrence during foetal and infancy stages associated with poor cognitive, motor and socio-emotional skills. However, information on the effects of various types of malnutrition on early childhood development (ECD) is limited in Nepal. To assess the association of stunting, wasting and underweight (three prominent forms of malnutrition) with the four domains of the ECD index (literacy-numeracy, physical, social-emotional and learning development) among children 36-59 months of age, we conducted an adjusted logistic regression using Nepal's national household Multiple Indicator Cluster Survey (MICS) 2019 data set. The study sample consisted of children aged 36-59 months (n = 2871). Children were considered developmentally on track if they met criteria in each of the four ECD domains. Regarding ECD status of children 36-59 months old, 35% of children were not developmentally on track for the ECD index. The adjusted odds ratio indicated that stunting was associated with lower odds of not being developmentally on track according to the ECD index as well as the literacy-numeracy, physical and learning domains of the ECD index. Likewise, underweight was associated with lower odds of not being developmentally on track according to the ECD index, primarily for ECD domains of literacy-numeracy, physical and learning. Notably, no association between wasting and ECD indicators was observed. Children's nutrition status impacts child development outcomes. Adding ECD interventions, such as responsive and stimulating caregiving, within nutrition programmes among children who are stunted and underweight could improve child development outcomes.

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.

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.

Rates of Bile Acid Diarrhoea After Cholecystectomy: A Multicentre Audit.

INTRODUCTION: Bile acid diarrhoea (BAD) can occur due to disruption to the enterohepatic circulation, e.g. following cholecystectomy. Post-cholecystectomy diarrhoea has been reported in 2.1-57.2% of patients; however, this is not necessarily due to BAD. The aim of this study was to determine the rates of bile acid diarrhoea diagnosis after cholecystectomy and to consider investigation practices. METHODS: A retrospective analysis of electronic databases from five large centres detailing patients who underwent laparoscopic cholecystectomy between 2013 and 2017 was cross-referenced with a list of patients who underwent 75SeHCAT testing. A 7-day retention time of <15% was deemed to be positive. Patient demographics and time from surgery to investigation were collected and compared for significance (p < 0.05). RESULTS: A total of 9439 patients underwent a laparoscopic cholecystectomy between 1 January 2013 and 31 December 2017 in the five centres. In total, 202 patients (2.1%) underwent investigation for diarrhoea via 75SeHCAT, of which 64 patients (31.6%) had a 75SeHCAT test result of >15%, while 62.8% of those investigated were diagnosed with bile acid diarrhoea (BAD). In total, 133 (65.8%) patients also underwent endoscopy and 74 (36.6%) patients had a CT scan. Median time from surgery to 75SeHCAT test was 672 days (SD ± 482 days). DISCUSSION/CONCLUSION: Only a small proportion of patients, post-cholecystectomy, were investigated for diarrhoea with significant time delay to diagnosis. The true prevalence of BAD after cholecystectomy may be much higher, and clinicians need to have an increased awareness of this condition due to its amenability to treatment. 75SeHCAT is a useful tool for diagnosis of bile acid diarrhoea.

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.

A comparative evaluation of the continuous and event-based modelling approaches for identifying critical source areas for sediment and phosphorus losses.

Proper identification of critical source areas (CSAs) is important for economic viability of any best management practices (BMPs) aimed at reducing sediment and phosphorus loads to receiving water bodies. Both continuous and event-based hydrologic and water quality models are widely used to identify and assess CSAs, however, their comparative assessment is lacking. In this study, we have used continuous Soil and Water Assessment Tool (SWAT) and event-based Agriculture Non-Point Source (AGNPS) pollution models to identify CSAs for sediment and phosphorus in a watershed in Ontario, Canada. Along with their original version, both models were re-conceptualized to incorporate saturation excess mechanism of runoff generation, which is also refereed as variable source area (VSA) integration. The models were set-up using high resolution spatial, crop- and land-management, and meteorological dataset; and calibrated with reasonable accuracy against streamflow, sediment and phosphorus concentration data at multiple locations. Threshold value (t-value) approach was used to identify CSA areas in the watershed. Results showed that both models were in agreement (up to 96% of fields) that summer season did not constitute hot-moments (<6% of the watershed area as CSAs) for both sediment and phosphorus. SWAT models identified winter (~50% of watershed area as CSA) and AGNPS models identified early spring (~50% of watershed areas as CSAs) season as the hot-moment for both sediment and phosphorus. Contrasting result, as indicated by low (1%) matching in field CSA potential, was observed in autumn season. In the same season, VSA integrated SWAT and AGNPS models showed better matching (43% for sediment and 31% for phosphorus), highlighting the importance of VSA integration in the models. Qualitative validation of model-based CSA potential with oblique aerial-photograph-based CSA potential in two soil moisture conditions (wetter and drier) indicated slightly better performance of the SWAT models, and over-prediction of the AGNPS models. However, a more comprehensive analysis based on more detailed field observations is needed to further confirm the results.

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.