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An improved understanding of the human lung necessitates advanced systems models informed by an ever-increasing repertoire of molecular omics, cellular, imaging, and pathological datasets. To centralize and standardize information across broad lung research efforts we expanded the LungMAP.net website into a new gateway portal. This portal connects a broad spectrum of research networks, bulk and single-cell multi-omics data and a diverse collection of image data that span mammalian lung development, and disease. The data are standardized across species and technologies using harmonized data and metadata models that leverage recent advances including those from the Human Cell Atlas, diverse ontologies, and the LungMAP CellCards initiative. To cultivate future discoveries, we have aggregated a diverse collection of single-cell atlases for multiple species (human, rhesus, mouse), to enable consistent queries across technologies, cohorts, age, disease, and drug treatment. These atlases are provided as independent and integrated queryable datasets, with an emphasis on dynamic visualization, figure generation, re-analysis, cell-type curation, and automated reference-based classification of user-provided single-cell genomics datasets (Azimuth). As this resource grows, we intend to increase the breadth of available interactive interfaces, supported data types, data portals and datasets from LungMAP and external research efforts.

Human disease states are biomolecularly multifaceted and can span across phenotypic states, therefore it is important to understand diseases on all levels, across cell types, and within and across microanatomical tissue compartments. To obtain an accurate and representative view of the molecular landscape within human lungs, this fragile tissue must be inflated and embedded to maintain spatial fidelity of the location of molecules and minimize molecular degradation for molecular imaging experiments. Here, we evaluated agarose inflation and carboxymethyl cellulose embedding media and determined effective tissue preparation protocols for performing bulk and spatial mass spectrometry-based omics measurements. Mass spectrometry imaging methods were optimized to boost the number of annotatable molecules in agarose inflated lung samples. This optimized protocol permitted the observation of unique lipid distributions within several airway regions in the lung tissue block. Laser capture microdissection of these airway regions followed by high-resolution proteomic analysis allowed us to begin linking the lipidome with the proteome in a spatially resolved manner, where we observed proteins with high abundance specifically localized to the airway regions. We also compared our mass spectrometry results to lung tissue samples preserved using two other inflation/embedding media, but we identified several pitfalls with the sample preparation steps using this preservation method. Overall, we demonstrated the versatility of the inflation method, and we can start to reveal how the metabolome, lipidome, and proteome are connected spatially in human lungs and across disease states through a variety of different experiments.

Background and objectives The role of diet in inflammatory bowel disease (IBD) remains incompletely understood. Studies have previously examined dietary practices in IBD, but none have specifically focused on older-onset disease. IBD may put vulnerable groups at risk of nutritional deficiency and associated complications, potentially heightened by comorbidities, frailty and polypharmacy. Our objective was to describe dietary practices and beliefs in older-onset IBD. Methods A questionnaire exploring dietary practices and beliefs was prospectively administered to 137 people with older-onset IBD attending gastroenterology clinics. Results Thirty-two percent believed diet was the initiating factor for their IBD. This was significantly more likely in people with Crohn's disease than ulcerative colitis (P = 0.05) and in those who felt limited in their dietary choices due to cost (P = 0.008). Forty-three percent believed diet could trigger IBD relapse and 68% avoided dietary components to avoid relapse. Most frequently avoided were spicy and fatty foods, carbonated drinks, red meat, alcohol and raw fruit and vegetables. Twenty-two percent of participants had tried a whole food exclusion diet, most frequently gluten- or lactose-free. Almost a third avoided eating out (29%) or eating the same meal as their family (32%) to prevent relapse. Respondents rarely relied upon healthcare professionals or patient support organisations for their dietary information. Conclusion Individuals with older-onset IBD report dietary practices with a high degree of consistency. Dietary avoidance may impact upon both nutritional and psychosocial wellbeing in this more vulnerable group and, as such, early dietetic assessment could help improve outcomes.

Background/Aims During the COVID-19 pandemic, inflammatory bowel disease clinics were converted to telephone clinics at St. Mark's Hospital in Harrow. This study assessed the response of patients and clinicians to remote telemedicine services, with the view of establishing whether there was scope for increasing the role of remote services in the inflammatory bowel disease clinics. Methods Clinicians administered a questionnaire to patients at the end of their appointments regarding their opinions on the telephone clinic format. Eleven questions used a 5-point Likert scale while a further three questions asked the patient for their comments on future clinics. Clinicians provided information about the patients' condition and management, as well as their own comments. Results Overall satisfaction with telephone clinics was found to be high among patients and clinicans, with many feeling that telephone clinics were more convenient. In total, 94.3% of patients said they would prefer either all telephone or a mix of phone and face-to-face clinics in the future. However, some patients felt that it was more complicated to have blood or stool tests done and roughly a quarter of patients were concerned that something could be missed without a physical examination. Conclusions High patient satisfaction can be achieved by delivering a mix of telephone, video and face-to-face clinics. In certain clinical situations, face-to-face clinics would be appropriate, such as patients with active diseases and first appointments. The pandemic is an opportunity respond to patients' preferences by increasing the range of remote care options.

Ravi Misra,1 Magali Sarafian,2 Alexandros Pechlivanis,3 Nik Ding,4 Jesus Miguens-Blanco,2 Julie McDonald,5 Elaine Holmes,2,6 Julian Marchesi,2,5,7 Naila Arebi1 1Gastroenterology, St Mark’s Academic Institute, London, UK; 2Division of Integrative Systems Medicine and Digestive Disease, Department of Surgery and Cancer, Imperial College, London, UK; 3Analytical Chemistry, Aristotle University of Thessaloniki, Thessaloniki, Greece; 4St Vincent’s Hospital, Inflammatory Bowel Disease Unit, Melbourne, Australia; 5School of Biosciences, Cardiff University, Cardiff, UK; 6Health Futures Institute, Murdoch and Edith Cowan Universities, Murdoch, Australia; 7Centre for Gut Health, Imperial College, London, UKCorrespondence: Ravi Misra, St. Mark’s Academic Institute, Imperial College, St. Mark’s Hospital, Watford Road, London, United Kingdom, Tel +44 0208 235 4124, Email r.misra15@imperial.ac.ukIntroduction: Ulcerative colitis (UC) differs across geography and ethnic groups. Gut microbial diversity plays a pivotal role in disease pathogenesis and differs across ethnic groups. The functional diversity in microbial-driven metabolites may have a pathophysiologic role and offer new therapeutic avenues.Methods: Demographics and clinical data were recorded from newly diagnosed UC patients. Blood, urine and faecal samples were collected at three time points over one year. Bacterial content was analysed by 16S rRNA sequencing. Bile acid profiles and polar molecules in three biofluids were measured using liquid-chromatography mass spectrometry (HILIC) and nuclear magnetic resonance spectroscopy.Results: We studied 42 patients with a new diagnosis of UC (27 South Asians; 15 Caucasians) with 261 biosamples. There were significant differences in relative abundance of bacteria at the phylum, genus and species level. Relative concentrations of urinary metabolites in South Asians were significantly lower for hippurate (positive correlation for Ruminococcus) and 4-cresol sulfate (Clostridia) (p< 0.001) with higher concentrations of lactate (negative correlation for Bifidobacteriaceae). Faecal conjugated and primary conjugated bile acids concentrations were significantly higher in South Asians (p=0.02 and p=0.03 respectively). Results were unaffected by diet, phenotype, disease severity and ongoing therapy. Comparison of time points at diagnosis and at 1 year did not reveal changes in microbial and metabolic profile.Conclusion: Ethnic-related microbial metabolite associations were observed in South Asians with UC. This suggests a predisposition to UC may be influenced by environmental factors reflected in a distinct gene-environment interaction. The variations may serve as markers to identify risk factors for UC and modified to enhance therapeutic response.Keywords: ulcerative colitis, microbiome, metabonomics

Objective The present study was conducted to delineate the prevalence and clinical features of portopulmonary hypertension in patients with hepatic cirrhosis. Possible associations between echocardiographic variables and portopulmonary hypertension were also explored. Methods A prospective, observational study was conducted between September 2017 and August 2018. Differences in demographics, clinical presentation, laboratory findings, and echocardiographic findings in cirrhosis patients with and without portopulmonary hypertension were compared. Results The prevalence of portopulmonary hypertension in patients with hepatic cirrhosis was found to be 9.3%. Hemoglobin was significantly lower among patients with portopulmonary hypertension compared to those without portopulmonary hypertension (5.50±0.68 g/dl vs. 7.26±1.43 g/dl, p=0.001). All patients with portopulmonary hypertension displayed right atrial (major: p=0.0001 and minor: p=0.001) and right ventricular (basal, p=0.0001; longitudinal, p=0.0001) dilation. Several variables such as right ventricular systolic pressure (p=0.0001), pulmonary artery diameter (major: p=0.0001; right: p=0.0001; and left: p=0.007), pulmonary vascular resistance (p=0.0001), tricuspid regurgitation (p=0.0001), pulmonary regurgitation peak pressure gradient (p=0.0001), pulmonary regurgitation end diastolic gradient (p=0.0001), left atrial dimension (major axis: p=0.002), left atrial volume (p=0.04), left ventricular outflow tract (p=0.001), inferior vena cava diameter (p=0.001), and inferior vena cava collapsibility (p=0.001) were higher in patients with portopulmonary hypertension compared to patients without portopulmonary hypertension. Conclusions The present study revealed a 9.3% prevalence of portopulmonary hypertension among patients with hepatic cirrhosis. Patients with portopulmonary hypertension displayed significantly lower haemoglobin levels, right and left ventricular dilation, and higher values of several echocardiographic variables as compared to those without portopulmonary hypertension.

Background Metabolic syndrome (MS) increases the risk of heart disease, stroke, and other complications. Aim The aim of this study was to assess the clinical and biochemical parameters of MS and its complications (cerebrovascular accidents, cardiovascular accidents, DN or chronic kidney disease (CKD) compared with healthy controls especially among the younger population in Northern India. Material and methods A total of 245 (healthy, MS and it's complicated) aged 18–70 years participated in the Open-Label, Single Centered; hospital-based random selection case-control comparative study. All anthropometric and biochemical assessment was done after proper consent. The metabolic syndrome was determined by IDF criteria. Results The key risk parameters in three groups i.e. Control, Metabolic syndrome, and Complicated was TG (96.5 ± 46.9, 194.1 ± 87.8, 148.0 ± 102.2). LDL (91.2 ± 27.2, 114.0 ± 31.8, 69.1 ± 42.5, BP (120.1 ± 9.9, 139.3 ± 13.3, 132.1 ± 15.0) and high fasting glucose (81.1 ± 13.7, 164.5 ± 84.3, 138.0 ± 74.5). The hs-CRP is also significantly increased in the complicated group. The subanalysis of data also indicates that younger middle age (36–55 years) group both male and female is obese, hypertensive, diabetic with lipid abnormality according to IDF criteria. Conclusion: The risk factors like high TG, low HDL, high BP, and high fasting glucose were found higher particularly in younger population which may lead to diagnosis & complications of diabetes, hypertension and lipid abnormality. Due to changing physiology in young and middle age population these individuals are moving towards metabolic syndrome easily and needs frequent monitoring, preventive checkups, and lifestyle changes to prevent complications.

BackgroundAccess to community rectoscopy might help to ease the burden on hospital services and reduce costs for the NHS. To assess this, a prospective multicentre observational phase I feasibility study of a novel digital rectoscope and telestration software for the triage of lower gastrointestinal (GI) symptoms was undertaken.AimTo determine if digital rectoscopy is feasible, acceptable, and clinically safe.Design & settingEvaluation of clinician case reports and patient questionnaires from patients recruited from five primary care centres.MethodAdults meeting 2-week wait (2WW) criteria for suspected lower GI cancer, suspected new diagnosis, or flare-up of inflammatory bowel disease (IBD) were enrolled. Examinations were performed by primary care practitioners using the LumenEye rectoscope. The CHiP platform allowed immediate remote review by secondary care. A prospective analysis was performed of patient and clinician experiences, diagnostic accuracy, and cost.ResultsA total of 114 patients were recruited and 110 underwent the procedure (46 [42%] females and 64 [58%] males). No serious adverse events were reported. Eighty-two (74.5%) patients reported that examination was more comfortable than expected, while 104 (94.5%) felt the intervention was most convenient if delivered in the community. Clinicians were confident of their assessment in 100 (87.7%) examinations. Forty-eight (42.1%) patients subsequently underwent colonoscopy, flexible sigmoidoscopy, or computed tomography virtual colonoscopy (CTVC). The overall sensitivity and specificity of LumenEye in identifying rectal pathology was 90.0% and 88.9%. It was 100% and 100% for cancer, and 83.3% and 97.8% for polyps. Following LumenEye examination, 19 (17.3%) patients were discharged, with projected savings of 11 305 GBP.ConclusionDigital rectoscopy in primary care is safe, acceptable, and can reduce referrals. A phase III randomised controlled trial is indicated to define its utility in reducing the burden on hospital diagnostic services.

Lung MAP HTC - BioRepository for Investigation of Neonatal Diseases of the Lung (BRINDL) 702.B.3 Combined SOP and Worksheet HTC_Lung_Tissue_Digestion_0100616rev061220 Purpose and Scope of the Procedure or Laboratory Assay 1.To dissociate and isolate single cell suspensions from human lung samples to meet the standards and needs of the Human Tissue Core. 2.This protocol covers manual gross dissociation of pieces of lung tissue (lobes or cubes) followed by enzymatic digestion and freezer storage as mixed populations of filtered and counted cells for which viability has been determined. 3.A separate protocol details the technique of freezing, thawing and further identifying and sorting these mixed cell populations. Scientific Principles or Validation of Procedure 1.Fujino et al. Am J Respir Cell Mol Biol. 2012 Apr;46(4):422-30 2.Barkauskas, C. E., Cronce, M. J., Rackley, C. R., Bowie, E. J., Keene, D. R., Stripp, B. R., ... & Hogan, B. L. (2013). Type 2 alveolar cells are stem cells in adult lung. The Journal of clinical investigation, 123(7), 3025.

Background and Aims Anti-tumour necrosis factor [anti-TNF] therapy is indicated for treatment of moderate to severe inflammatory bowel disease [IBD], but has a primary non-response rate of around 30%. We aim to use metabonomic and metataxonomic profiling to identify predictive biomarkers of anti-TNF response in Crohn’s disease. Methods Patients with luminal Crohn’s disease, commencing anti-TNF therapy, were recruited with urine, faeces, and serum samples being collected at baseline and 3-monthly. Primary response was defined according to a combination of clinical and objective markers of inflammation. Samples were measured using three UPLC-MS assays: lipid, bile acid, and Hydrophillic Interaction Liquid Chromatography [HILIC] profiling with 16S rRNA gene sequencing of faeces. Results Samples were collected from 76 Crohn’s disease patients who were anti-TNF naïve and from 13 healthy controls. There were 11 responders, 37 non-responders, and 28 partial responders in anti-TNF-treated Crohn’s patients. Histidine and cysteine were identified as biomarkers of response from polar metabolite profiling [HILIC] of serum and urine. Lipid profiling of serum and faeces found phosphocholines, ceramides, sphingomyelins, and triglycerides, and bile acid profiling identified primary bile acids to be associated with non-response to anti-TNF therapy, with higher levels of phase 2 conjugates in non-responders. Receiver operating curves for treatment response demonstrated 0.94 +/ -0.10 [faecal lipid], 0.81 +/- 0.17 [faecal bile acid], and 0.74 +/- 0.15 [serum bile acid] predictive ability for anti-TNF response in Crohn’s disease. Conclusions This prospective, longitudinal cohort study of metabonomic and 16S rRNA gene sequencing analysis demonstrates that a range of metabolic biomarkers involving lipid, bile acid, and amino acid pathways may contribute to prediction of response to anti-TNF therapy in Crohn’s disease. Podcast This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast

Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) comprise impairment of multiple cognitive domains and cause significant morbidity. International HIV Dementia Scale (IHDS) is a quite sensitive and specific method for screening for HAND, and Modified Mini-Mental State Examination (3MS), though nonspecific, contains more parameters for screening for neurocognition. Hence, we compared 3MS and IHDS as screening tools for HAND with an aim to find out which was a better screening tool for HAND.Using 3MS and IHDS, we assessed the cognitive status of 200 HIV-positive patients (65% males) and 84 controls, presenting to the Department of Medicine, King George's Medical University, Lucknow, India from September 2015 to September 2019.According to 3MS, 42 (21%) HIV-positive patients were neurocognitively impaired (mean 76.24 ± 1.51), and 158 (79%) patients were not (mean 87.02 ± 4.16). As per IHDS, 185 (92.5%) HIV patients were neurocognitively impaired (mean 8.45 ± 0.88), and 15 (7.5%) patients were not (mean 11.13 ± 0.35). The mean 3MS score of controls was 87.56 ± 4.26, and the IHDS score was 9.73 ± 1.00. According to Patient Health Questionnaire-9 (PHQ-9), moderate depression occurred in only 3.5% of the patients, and the rest had only minimal or mild depression. In IHDS, psychomotor speed was the most affected parameter, whereas in 3MS, similarities were the most affected.IHDS may be over diagnosing neurocognitive impairment in HIV patients due to difficulty in understanding the test, especially psychomotor speed testing. 3MS may be more accurate for detecting neurocognitive impairment in HIV patients, and scale combining both these methods may be a still better choice.

Background and Aims Distal attachments placed on the colonoscope tip may positively affect performance by assisting insertion and polyp detection. The original Endocuff (ARC Medical Design, Leeds, United Kingdom) appears to improve adenoma detection rate (ADR), but no data assess the performance of the second-generation Endocuff Vision. Methods A pilot service evaluation study (April 2013 to September 2014) was conducted on patients with positive fecal occult blood tests within the National Bowel Cancer Programme during 3 consecutive periods: precuff/no device used, during-cuff/device used, and postcuff/no device used. During the middle period the use of the Endocuff Vision by the 4 screening-accredited colonoscopists was discretional (nonrandomized design). Data were analyzed using pairwise comparisons during the 3 designated periods to examine key performance indicators: adenoma detection, procedural time, sedation requirements, and patient comfort. Results Four hundred ten complete colonoscopies were performed (137 precuff, 136 cuff, and 137 postcuff period). Overall, there was a notable increase in the mean ADR of 16% (P Conclusions In this pilot service evaluation study, the use of the Endocuff Vision appears to be associated with an improvement in overall colonoscopy operator performance. We found increased ADR and MAP as well as decreased time for colonoscope insertion and withdrawal time with no increase in sedation requirements or patient discomfort.

BACKGROUND Sepsis is commonly encountered in patients of cirrhosis of liver and is associated with worse outcome. Traditional culture methods commonly used to diagnose sepsis in such patients is positive only in 50-70% of cases and take longer time. Therefore, surrogate marker such as Procalcitonin (PCT) and C-Reactive Protein (CRP) may be useful to identify patients of early sepsis with increased sensitivity and in shorter time. The aim of the study is to- 1. Evaluate the role of PCT and CRP in patients with cirrhosis of liver with and without sepsis. 2. Find correlation of levels of procalcitonin and CRP with clinical and biochemical parameters of severity of cirrhosis as well as to find out its prognostic implications. MATERIALS AND METHODS A cross-sectional observational study was conducted in the Department of Medicine, King George Medical University, Lucknow, India, over a period of one year. A detailed history and clinical examination was performed in all enrolled patients. Along with routine tests done in patients of cirrhosis of liver, procalcitonin and CRP levels are performed. RESULTS PCT and CRP levels were significantly higher in patients with sepsis as compared to patients without sepsis. PCT and CRP levels were also significantly higher in patients who presented with complications of cirrhosis like variceal bleed, hepatic encephalopathy and severe ascites as compared to patients without these complications. Significantly higher rate of mortality and longer duration of hospital stay was observed in patients with higher values of PCT and CRP levels. CONCLUSION Procalcitonin and CRP levels are significantly raised in patients of cirrhosis with sepsis. These biomarkers gives us an opportunity to diagnose sepsis in early stages, so that early antibiotic therapy can be initiated and sepsis precipitated complications of cirrhosis can be prevented leading to favourable outcome of the patient. So, we recommend that PCT and CRP levels should always be measured in patients of cirrhosis with suspected sepsis.

Aim To describe the incidence and phenotype of IBD and distribution within ethnic groups. Methods Adult patients (>16 years) with newly diagnosed IBD (fulfilling Copenhagen diagnostic criteria) were prospectively recruited over one year in 5 urban catchment areas with high South Asian population. Patient demographics, ethnic codes, disease phenotype (Montreal classification), disease activity and treatment within 3 months of diagnosis were recorded onto the Epicom database. Results Across a population of 2,271,406 adults, 339 adult patients were diagnosed with IBD over one year: 218 with UC (64.3%), 115 with CD (33.9%) and 6 with IBDU (1.8%). The crude incidence of IBD, UC and CD was 17.0/100,000, 11.3/100,000 and 5.3/100,000 respectively. The age adjusted incidence of IBD and UC were significantly higher in the Indian group (25.2.100,000 and 20.5/100,000) compared to White European (14.9/100,000, p=0.009 and 8.2/100,000, p

[Image: see text] A targeted ultrahigh-performance liquid chromatography tandem mass spectrometry with electrospray ionization (UHPLC-ESI-MS/MS) method has been developed for the quantification of tryptophan and its downstream metabolites from the kynurenine and serotonin pathways. The assay coverage also includes markers of gut health and inflammation, including citrulline and neopterin. The method was designed in 96-well plate format for application in multiday, multiplate clinical and epidemiology population studies. A chromatographic cycle time of 7 min enables the analysis of two 96-well plates in 24 h. To protect chromatographic column lifespan, samples underwent a two-step extraction, using solvent protein precipitation followed by delipidation via solid-phase extraction (SPE). Analytical validation reported accuracy of each analyte

Prem Chandra Misra arrived in the UK in 1968 and specialised in psychiatry. He met his future wife, Sandhya (a fellow psychiatrist), while working in Bolton in 1969. They subsequently settled in …

Background The United Registries for Clinical Assessment and Research (UR-CARE) is a validated pan-European database developed by the European Crohn’s and Colitis Organisation (ECCO) to support clinical practice for patients with inflammatory bowel disease (IBD). ECCO has published guidelines to reduce variation in care. We examined the value of UR-CARE database to improve care in a cohort of newly-diagnosed IBD patients. Methods All patients with a new diagnosis of IBD within 6 months attended a New Diagnosis Clinic (NDC). Prior to registering patients, the purpose of UR-CARE database was explained. Patients who consented to have their clinical data added to the database signed a consent form. Mandatory fields and additional data that reflected quality of care were inputted. Descriptive statistics summarised the findings. The association between consent and disease activity or gender was examined using a chi-square test and for age using a two-sample t-test. Results Twenty-five out of 29 newly diagnosed patients consented for data inclusion in UR-CARE (13 males). Median age was 44 (range 18–77). Fourteen had ulcerative colitis (UC), 8 had Crohn’s disease (CD) and 3 had unclassified IBD. 8.3% reported extra-intestinal manifestations within 6 months of diagnosis. 17/25 patients had active disease. The patients that did not consent consisted of 2 males, 3/4 had active disease and mean age was 44.4 (SD 16.1) compared with 36.3 (SD 19.4) consenters. Through the database we noted that not all mandatory diagnostic tests were requested at the time of hospital visit: 4/14 UC patients did not have a full colonoscopy and 3/8 CD patients lacked a small bowel imaging or capsule endoscopy. Only 4 out of 14 UC patients and 2 out of 8 CD patients were prescribed steroids within 6 months of their diagnosis. The 7 patients with missing investigations were identified and tests subsequently booked in line with guidelines. There was no association between consent and disease activity (p = 0.78), gender (p = 0.94) and age (p = 0.37). Conclusion In newly diagnosed IBD cohort, most patients consented to inclusion in UR-CARE database. There were no contributing factors associated with patient consent. The easily accessible visualisation of our data detected incomplete diagnostic tests and initiated actions to improve care early on in the disease course. UR-CARE offers potential to deliver high quality IBD care by aligning practice against ECCO guidelines. Attention to data-sharing legal and administrative barriers offers a promise for large scale studies and foster collaborative research networks.

Background and Aims: Few population-based cohort studies have assessed the disease course of ulcerative colitis [UC] in the era of biological therapy and widespread use of immunomodulators. The aim of this study was to assess the 5-year outcome and disease course of patients with UC in the Epi-IBD cohort.Methods: In a prospective, population-based inception cohort of unselected patients with UC, patients were followed up from the time of their diagnosis, which included the collection of their clinical data, demographics, disease activity, medical therapy, and rates of surgery, cancers, and deaths. Associations between outcomes and multiple covariates were analysed by Cox regression analysis.Results: A total of 717 patients were included in the study. During follow-up, 43 [6%] patients underwent a colectomy and 163 [23%] patients were hospitalised. Of patients with limited colitis [distal to the left flexure], 90 [21%] progressed to extensive colitis. In addition, 92 [27%] patients with extensive colitis experienced a regression in disease extent, which was associated with a reduced risk of hospitalisation (hazard ratio [HR]: 0.5 95% CI: 0.3-0.8]. Overall, patients were treated similarly in both geographical regions; 80 [11%] patients needed biological therapy and 210 [29%] patients received immunomodulators. Treatment with immunomodulators was found to reduce the risk of hospitalisation [HR: 0.5 95% CI: 0.3-0.8].Conclusions: Although patients in this population-based cohort were treated more aggressively with immunomodulators and biological therapy than in cohorts from the previous two decades, their disease outcomes, including colectomy rates, were no different. However, treatment with immunomodulators was found to reduce the risk of hospitalisation.

International Journal of Advanced Research (IJAR)

AIM To summarise the current literature and define patterns of disease in migrant and racial groups. METHODS A structured key word search in Ovid Medline and EMBASE was undertaken in accordance with PRISMA guidelines. Studies on incidence, prevalence and disease phenotype of migrants and races compared with indigenous groups were eligible for inclusion. RESULTS Thirty-three studies met the inclusion criteria. Individual studies showed significant differences in incidence, prevalence and disease phenotype between migrants or race and indigenous groups. Pooled analysis could only be undertaken for incidence studies on South Asians where there was significant heterogeneity between the studies [95% for ulcerative colitis (UC), 83% for Crohn’s disease (CD)]. The difference between incidence rates was not significant with a rate ratio South Asian: Caucasian of 0.78 (95%CI: 0.22-2.78) for CD and 1.39 (95%CI: 0.84-2.32) for UC. South Asians showed consistently higher incidence and more extensive UC than the indigenous population in five countries. A similar pattern was observed for Hispanics in the United States. Bangladeshis and African Americans showed an increased risk of CD with perianal disease. CONCLUSION This review suggests that migration and race influence the risk of developing inflammatory bowel disease. This may be due to different inherent responses upon exposure to an environmental trigger in the adopted country. Further prospective studies on homogenous migrant populations are needed to validate these observations, with a parallel arm for in-depth investigation of putative drivers.

Dengue fever is caused by mosquito-borne arboviral infection that has become a public health concern globally. Recently, an alarming rise of dengue has also been seen in India. Hence the study was undertaken to know profile of clinical manifestations and laboratory findings during the evolution of dengue fever.In this study, retrospective data analysis was done in 216 seropositive dengue patients admitted between January to December 2014 in department of medicine at a north Indian care hospital. The tests analyzed were blood counts, serum electrolytes, liver function tests, kidney function tests, chest x-ray and other relevant investigations.Males were commonly affected and the most exposed age group was found to be18-35 years. The seropositive case rate for dengue was 56% for NS1 antigen and 36% for IgM. There was rural dominancy of cases with a peak in September. Fever was the most common clinical feature followed by headache, myalgia, backache, nausea and abdominal pain. Petechia was most common haemorrhagic manifestation. Common laboratory findings included 89.35% decreased Platelet counts (100 000/cmm), 67.59% increased hematocrit (45%) and 58.33% deranged liver function test. There was no reported mortality in dengue.From prompt and proper treatment could prevent deaths in moderate and severe dengue. Atypical presentations of dengue should be kept in mind so as not to miss the cases. Increased community awareness and vector control measures need to be strengthened during peri-monsoon period to reduce burden of dengue cases.

Background IBD is a chronic condition that affects young and older people. Co-existing diseases are common. Patient-centred care includes education and support to empower patients and is a recognised dimension of high-quality care. Patient empowerment with knowledge, skills and confidence (‘patient activation’) is associated with better outcomes in many chronic diseases. We aimed to measure patient activation in recently diagnosed IBD patients and to identify factors associated with levels of activation. Methods A NDC was set up at St Mark’s Hospital to offer patients education, information resources and signposts to verified information sources. Patient activation was measured using the Patient Activation Measure (PAM®) tool (Insignia Health) before and after the first consultation. PAM® is a validated questionnaire with 13 questions to generate an activation score ranging from 1 to 4. Non-activation was defined as PAM levels 1 and 2. Demographic (age in years (SD)), disease specific characteristics and anxiety (Generalised Anxiety Disorder Scale, GAD-2) and depression [Patient Health Questionnaire (PHQ-2)] data were collated at the first visit. The National Statistics Socio-economic classification (NS-SEC) was used to classify socio-economic status (SES). Categorical variables were analysed with chi-square test and numerical variables with Student’s t-test. Results Twenty-nine patients (51.7% male) attended NDC (ulcerative colitis = 15, Crohn’s disease = 10, unclassified IBD = 4). 28 completed PAM questionnaires. Mean age was 43.2 ( ± 16.4). 5/28 had a family history of IBD, 6/28 were smokers, 11/28 had another chronic condition, and 16/28 were of non-White ethnic background. Sixty-nine% had active disease. SES and psychological scores were available for 14/28 and 16/28 patients, respectively. Fifty per cent (14/28) of patients were non-activated before NDC; 57.1% (8/14) showed an improvement in activation after NDC. Mean age for activated and non-activated patients was 40.6 ( ± 19.0) and 46.6 ( ± 13.9), respectively (p = 0.35). There was no association between gender, family history, smoking, co-morbidity, ethnic background and SES with activation. None of the four patients (4/16) who scored for anxiety or depression were activated compared with 50% (6/12) of non-anxious/depressed patients (p = 0.07). No patients (0/7) in intermediate or higher SES were activated compared with 43% (3/7) of lower SES (p = 0.05). Conclusion Most non-activated patients had improved activation after attending NDC. Anxiety and depression may contribute to non-activation. Early assessment of patient activation may guide healthcare providers to offer individualised support. Further studies to evaluate the sustainability of patient activation and its effect on clinical outcomes are ongoing.

Objective To evaluate the requirement for protein kinase Cβ (PKCβ) in the development of lupus in mice, and to explore the potential of targeting PKCβ as a therapeutic strategy in lupus. Methods Congenic mice bearing the disease loci Sle1 or Sle1 and Sle3, which represent different stages of severity in the development of lupus, were crossed with PKCβ-deficient mice. The effect of PKCβ deficiency in lupus development was analyzed. In addition, the effects of the PKCβ-specific inhibitor enzastaurin on the survival of B cells from mice with lupus and human 9G4-positive B cells as well as the in vivo effect of enzastaurin treatment on the development of lupus in Sle mice were investigated. Results In Sle mice, PKCβ deficiency abrogated lupus-associated phenotypes, including high autoantibody levels, proteinuria, and histologic features of lupus nephritis. Significant decreases in spleen size and in the peritoneal B-1 cell population, reduced numbers of activated CD4 T cells, and normalized CD4:CD8 ratios were observed. PKCβ deficiency induced an anergic B cell phenotype and preferentially inhibited autoreactive plasma cells and autoantibodies in mice with lupus. Inhibition of PKCβ enhanced apoptosis of both B cells from Sle mice and human autoreactive B cells (9G4 positive). Treatment of Sle mice with the PKCβ-specific inhibitor enzastaurin prevented the development of lupus. Conclusion This study identifies PKCβ as a central mediator of lupus pathogenesis, suggesting that PKCβ represents a promising therapeutic target for the treatment of systemic lupus erythematosus. Moreover, the results indicate the feasibility of using a PKCβ inhibitor for the treatment of lupus.

Introduction: Liver plays an important role in the metabolism of thyroid hormones. It also has a dominant role in the production and secretion of thyroid binding globulin. So, patients of cirrhosis of liver may be clinically euthyroid but thyroid hormones and thyroid binding globulin are altered. Low free T3 and free T4 along with increased reverse T3 (rT3) and decreased T3:T4 ratio are the common alterations observed in thyroid profile of such patients. Aim: To evaluate thyroid profile in patients with cirrhosis of liver and correlation of thyroid profile with clinical and biochemical parameters of severity in patients with cirrhosis of liver. Materials and Methods: A observational, cross-sectional study was conducted at a tertiary care hospital evaluating thyroid profile in 102 patients with cirrhosis of liver. Results: Low free T3 and T4 was found in 72.5% and 26.47% of patients with cirrhosis of liver respectively. TSH towards the upper limit of normal range was observed in 52.3% of patients. Low free T3 and free T4 was found to be inversely related to the severity of liver disease. A significant correlation was also found between low free T3 levels, hyponatremia (p=0.004) and raised INR (p=0.038). Similarly, a significant correlation was also observed between low free T4 levels, serum bilirubin (p=0.049) and SGPT (p=0.008) levels. Conclusion: Derangement in thyroid profile is common in patients with cirrhosis of liver. Low free T3 and T4 levels are associated with more severe liver injury and may be used for prognostication in patients with cirrhosis of liver.

BACKGROUND & AIMS The inflammatory bowel diseases (IBD) ulcerative colitis (UC) and Crohn’s disease (CD) cause significant morbidity and are increasing in prevalence among all populations, including African Americans. More than 200 susceptibility loci have been identified in populations of predominantly European ancestry, but few loci have been associated with IBD in other ethnicities. METHODS We performed 2 high-density, genome-wide scans comprising 2345 cases of African Americans with IBD (1646 with CD, 583 with UC, and 116 inflammatory bowel disease unclassified) and 5002 individuals without IBD (controls, identified from the Health Retirement Study and Kaiser Permanente database). Single-nucleotide polymorphisms (SNPs) associated at P RESULTS We detected SNPs at HLA-DRB1, and African-specific SNPs at ZNF649 and LSAMP, with associations of genome-wide significance for UC. We detected SNPs at USP25 with associations of genome-wide significance for IBD. No associations of genome-wide significance were detected for CD. In addition, 9 genes previously associated with IBD contained SNPs with significant evidence for replication (P CONCLUSIONS We performed a genome-wide association study of African Americans with IBD and identified loci associated with UC in only this population; we also replicated IBD, CD, and UC loci identified in European populations. The detection of variants associated with IBD risk in only people of African descent demonstrates the importance of studying the genetics of IBD and other complex diseases in populations beyond those of European ancestry.

Introduction Inflammatory bowel disease (IBD) is influenced by environmental and genetic factors which alters the gut microbiota. The human gut microbiota is involved in the maintenance of its host physiological functions and imbalance in the microbial population and its metabolic signatures may lead to disease activity and phenotype. We aimed to investigate the variations occurring in lipid metabolism between Crohn’s disease (CD) vs. controls in serum and faeces by profiling using a metabonomic approach. Methods Serum and faeces were collected from moderate to severe Crohn’s disease patients prior to commencement of anti- TNF. Sample preparation: Protein precipitation with isopropanol was implemented on serum and faeces samples and prepared by biphasic extraction.Lipid profiling: The method was performed on Waters Acquity UPLCTM combined with Waters Q-Tof PremierTM mass spectrometerData processing: OPLS-DA was carried out on the XCMS extracted intensities using SIMCA P+ v13 and Matlab.Lipids annotation was derived by searching m/z against online databases (METLIN, Lipidmaps and HMDB). Results Multivariate analyses between healthy and CD patients were performed to characterise lipid profile differences.Significant separation was observed in both serum and faeces between the two groups (Figure 1). Lipid metabolism is affected in CD patients compared to healthy controls. Correlation analysis showed that several triglyceride (TG) species were significantly associated with CD. TGs with medium to long chain fatty acid length and with saturations were identified at increased levels in CD patients (Figure 2). TGs with saturated fatty acids were prominent in faeces compare to serum. Moreover, TGs found in faeces were in higher concentration than in serum. Conclusion The metabonomic study showed profound variations in both serum and faeces of CD patients. These results highlight the association between the gut microbiota and mucosal barrier function which has downstream effect on lipid metabolism and inflammation in IBD. This metabonomic approach offers potential application in diagnosing CD. Disclosure of Interest None Declared

Munna Lal Patel,1 Rekha Sachan,2 Ravi Misra,3 Ritul Kamal,4 Radhey Shyam,5 Pushpalata Sachan6 1Department of Medicine, King George Medical University, Lucknow, India; 2Department of Obstetrics and Gynaecology, King George Medical University, Lucknow, India; 3Department of Internal Medicine, King George Medical University, Lucknow, India; 4Epidemiology Division, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow, India; 5Department of Geriatric Intensive Care Unit, King George Medical University, Lucknow, India; 6Department of Physiology, Career Institute of Medical Sciences, Lucknow, India Background: Chronic kidney disease (CKD) is a worldwide public health problem. Recently urinary NGAL (uNGAL) has been proven to be a useful (potentially ideal) biomarker for early detection of CKD. The aim of the present study was to examine the correlation of uNGAL with severity of renal impairment in CKD and to evaluate its prognostic value in these subjects. Methods: This was a prospective study carried out over a period of 24 months in subjects with CKD due to primary chronic glomerulonephritis. New cases of CKD stage II, III, IV aged between 18 and 65 years were enrolled as per KDIGO (Kidney Disease: Improving Global Outcomes) guidelines 2012. A total of 90 subjects completed the study up to the end-point. The primary follow-up end-point was 18 months, or decreased glomerular filtration rate of less than 15 mL/min. Secondary follow-up end-point was the number of subjects who expired during this period. Results: Multiple regression model of estimated glomerular filtration rate showed significant associations with log uNGAL (β=0.38, P3.51 unit had a renal survival rate of 14.7%. Conclusion: Our study result showed that uNGAL has a positive correlation with disease severity which signifies the prognostic importance of uNGAL in CKD. Keywords: urinary NGAL, chronic kidney disease, prognostic significance

Introduction Previous studies suggest changing incidence and prevalence of Inflammatory Bowel Disease (IBD) in migrant groups, particularly South Asians. Most of these studies were retrospective and within local hospital settings. They also suggest a different phenotype: pan-colonic ulcerative colitis (UC) was commoner in migrants from India compared with Caucasians. One study in East London reported on differing phenotype of Crohn’s disease (CD) in Bangladeshis; they developed perianal complications, received anti-TNFs earlier and underwent surgery later than Caucasians. We examined the ethnic diversity of patients with IBD attending hospitals in England. Method We identified patients from a national hospital episodes statistics (HES) database between 1997–2012. The database captures all hospital episodes between these dates. Patients were identified according to ICD-10 diagnosis code; K51 for UC and K52 for CD. Only patients with a documented ethnicity code were included. Results Patients with an ethnicity code and a diagnosis of UC and CD are shown in Table 1. Only 35.3% of cases had an ethnicity code. The majority of patients were of White European (Caucasian) descent. In Bangladeshis, CD was commoner than UC in contrast to Indian and Pakistani ethnic groups where UC was commoner than CD. Conclusion Bangladeshis are more likely to have CD compared with Indians and Pakistanis and require more hospital interventions for CD than UC. This may represent a more aggressive phenotype consistent with previous literature. This data is limited by the nature of the HES database: retrospective, hospital episodes and incomplete coding for ethnicity. Prospective studies are needed to validate these findings and explore underlying reasons for the difference. Disclosure of interest None Declared.

Introduction Previous epidemiological studies suggest a higher rate of pan-colonic disease in South Asians (SA) compared with Caucasians. There is limited data on disease severity across ethnic groups. Refractory disease and development of dysplasia indicate aggressive disease and are both indications for colectomy. The aim of the study was to compare the risk of colectomy for ulcerative colitis (UC) in SA migrants to Caucasians. Method Patients with UC were identified from a national administrative dataset (Hospital Episode Statistics – HES) between 1997–2012 according to ICD-10 diagnosis code K51 for UC. From the cases coded for ethnicity, colectomy cases were identified according to the Office of Population Censuses and Surveys (OPCS) codes. The colectomy rate for each ethnic group was calculated as the proportion of patients who underwent colectomy from the total UC cases for that group. The median age at time of colectomy was calculated for each ethnic group. Chi-squared testing was used to determine significant differences in colectomy rate and Kruskal-Wallis test to ascertain differences in age at colectomy between ethnic groups. Results Of 212,430 UC cases, 74,988 (35.3%) were coded for ethnicity. Of these cases most were White Europeans (Caucasians) 69,208/74,988 (92.3%). The SA group consisted of: 1,954/74,988 (2.6%) Indian, 832/74,988 (1.1%) Pakistani and 129/74,988 (0.2%) Bangladeshi ([Table 1][1]). Indians had a significantly higher colectomy rate than White Europeans (10.8% vs 7.4%, p < 0.001). In contrast Pakistanis had a similar (7.0%) and Bangladeshis a significantly lower (4.7%) colectomy rate than the White European group. (7.4%, p < 0.001). SAs undergoing colectomy were significantly younger than White Europeans for each ethnic group (median age; Bangladeshis - 29 years, Pakistanis - 37 years and Indians – 41 years, compared with White Europeans – 49 years, p < 0.001). View this table: Abstract PTH-063 Table 1 Colectomy rate in UC patients by ethnicity Conclusion The colectomy rate is higher in Indians compared to White Europeans. Across SA ethnic groups there are differences in colectomy rate. All SA groups required a colectomy for UC at a younger age than White Europeans. These findings suggest a more aggressive phenotype in SAs and should be validated with a prospectively recruited ethnic cohort. This will also allow examination of contributing factors. Disclosure of interest None Declared. [1]: #T1

Duodenal diverticula are commonly located in the second part of the duodenum and are usually asymptomatic. We report a 45-year-old man with massive bleeding from a duodenal diverticulum located beyond the second part of the duodenum. The diverticulum was excised, and the patient. has remained asymptomatic over the next 12 months.