To study the neurodevelopmental status of offsprings of mothers with gestational diabetes (OGDM) aged 3½ mo. This cross-sectional study was conducted at a tertiary hospital, New Delhi which included infants aged 3½ mo (+1 wk) who were either offsprings of women with gestational diabetes (cases) or infants of mothers without gestational diabetes mellitus presenting to tertiary care public hospital in India from January, 2018 through March, 2019, with enrollment of infants done between 10 April, 2018 and 30 March, 2019. The development quotient (DQ) using Developmental Assessment Scales for Indian Infants (DASII) was calculated as Motor DQ, Mental DQ and a composite DQ. The mean motor DQ of the enrolled infants was 101.7 (12.02); it was significantly lower for OGDM than controls [101 (1.41) vs. 109.5 (10.6); P <0.001]. The mean mental DQ of the enrolled infants was 88.9 (12.0); it was significantly lower for OGDM than the control group [84 (9.89 vs. 88 (8.48); P = 0.03]. The total development quotient for the enrolled infants was 95.3 (11.3). The total development quotient for study group was significantly lower than the control group [92.5 (5.65) vs. 98.75 (9.54); P = 0.001]. The mean motor, mental total DQ of offsprings of mothers with GDM were significantly lower than those born to mothers without GDM. Hence follow up, early intervention should be considered for this high risk group.

PurposeThe impact of IUGR on holistic growth of an infant is established however, limited evidence has been reported regarding its implication on eruption of deciduous dentition.AimComparative evaluation of eruption of deciduous teeth among infants born after low risk pregnancy and infants diagnosed with Intra Uterine Growth Restriction (IUGR)MethodsThe cross-sectional study included 110 neonates recruited at birth using stratified random sampling based on inclusion and exclusion criteria. Neonates diagnosed without IUGR were allocated to Group I (n = 55) and those diagnosed with IUGR were allocated to Group II (n = 55). Perinatal case history was obtained followed by intraoral examination at birth, 6 months and monthly up to 1 year or till first evidence of teeth eruption.ResultsThe first evidence of eruption of deciduous teeth was found delayed in Group II (p = 0.0001). The mean gestational age at delivery, estimated fetal weight, frequency of NICU admission, birth weight and infant weight at 6 months was found statistically higher (p = 0.001) in Group I.ConclusionFirst evidence of deciduous teeth eruption was found delayed among IUGR infants therefore, IUGR along with prematurity, LBW, LSCS delivery, NICU admission can be considered as risk factor for delayed eruption.

Purulent myositis is an acute, intramuscular bacterial infection involving abscess formation most commonly affecting the quadriceps, hamstring and gluteal muscles. We present a case of extensive purulent myositis of the thigh and lower leg caused by bowel perforation below the peritoneal reflection secondary to rectal cancer. Cases of lower limb and perineal purulent myositis should raise suspicion of rectal perforation and should prompt investigations to exclude rectal malignancy.

Crohn's disease (CD) has traditionally been associated with weight loss and low BMI, yet paradoxically obesity has recently been suggested as a risk factor for CD, but not for ulcerative colitis (UC). We therefore hypothesized that the relation between BMI and CD is U shaped.To conduct a large population-based prospective cohort study of BMI and later risk of IBD, taking age at IBD diagnosis into account.A cohort of 74,512 women from the Danish National Birth Cohort, with BMI measured pre-pregnancy and 18 months after delivery, was followed for 1,022,250 person-years for development of IBD, according to the Danish National Patient Register. Associations were tested by Cox regression.Overweight subjects (25≤BMI<30 kg/m2) had the lowest risk of CD, whereas obesity (BMI≥30kg/m2) increased the risk of CD at all ages, and low BMI (BMI<18.5kg/m2) associated with CD diagnosed at age 18-<40 years. Hence, using normal weight subjects as the reference, adjusted HRs for risk of developing CD (at age 18-<40 years) were 1.8(95%CI, 0.9-3.7) for underweight, 0.6(0.3-1.2) for overweight, and 1.5(0.8-2.7) for obese individuals (pre-pregnancy BMI). HRs were greater for BMI determined 18 months after delivery. Splines for CD risk according to waist:height ratio confirmed a U-shaped relationship with CD occurring <40 years, and a linear relationship with CD diagnosed at age 40+. There was no relationship between BMI and risk of UC.For the first time, we demonstrate that both high BMI and low BMI are risk factors for CD. Underweight may be a pre-clinical manifestation of disease being present many years before onset with obesity being a true risk factor. This raises the question as to whether there may be two distinct forms of CD.

s(HR 1.18; 95% CI 1.04-1.35),but not anti-TNF therapy.The increased risk was limited to follow-up after IBD diagnosis (figure).When the HZV utilization was compared among those older than age 60 (recommended age for HZV in the entire time period of approval) during the follow-up, there was no difference between those with and without IBD (univariate OR 1.13; 95% CI 0.95-1.35;multivariate, adjusting for socioeconomic status OR 1.14; 95% CI 0.96-1.36).Median age at vaccination was 67.Among those with IBD, men were less likely to receive HZV (OR 0.63, 95% CI 0.45-0.88),but there was no difference in HZV with IBD duration, immunomodulator/biological exposure, number of physician visits or socio-economic status.Conclusion: Despite a greater risk of HZ among those with IBD, utilization of HZV is not increased in the IBD cohort.Since a high proportion of individuals are exposed to thiopurines (a predictor of HZ risk) and HZV has been traditionally contraidicated once immunosuppressants are started, HZV should be considered for all individuals at IBD diagnosis especially with older age of IBD onset. Tu1797

The incidence of Crohn disease (CD) has been increasing and surgery needs to be contemplated in a substantial number of cases. The relevant advent of biological treatment has changed but not eliminated the need for surgery in many patients. Despite previous publications on the indications for surgery in CD, there was a need for a comprehensive review of existing evidence on the role of elective surgery and options in pediatric patients affected with CD. We present an expert opinion and critical review of the literature to provide evidence-based guidance to manage these patients. Indications, surgical options, risk factors, and medications in pre- and perioperative period are reviewed in the light of available evidence. Risks and benefits of surgical options are addressed. An algorithm is proposed for the management of postsurgery monitoring, timing for follow-up endoscopy, and treatment options.

Appendagitis is an uncommon clinical entity, often not recognised, and mistaken for more serious infective conditions. We describe a proven case of appendagitis which occurred after confirmed appendicitis. We postulate that this condition can coexist with appendicitis and indeed may be the result of coinflammation. This has several implications. Firstly, clinicians must retain an index of suspicion for this condition in a patient with localised abdominal pain which occurs after appendicitis. Secondly, it would be reasonable to suggest careful examination of colocated appendages in a patient with an otherwise normal-appearing appendix. Treatment might require laparoscopic resection, as performed in this case.

We previously reported an improvement in symptoms in Crohn’s disease following an IgG4-guided exclusion diet in an open-label study. We aimed to evaluate, in a double-blinded randomized sham-controlled setting, the efficacy of IgG4-guided diet in improving quality of life in patients with Crohn’s disease.

BACKGROUND:Faecal calprotectin (FC) is one of the most widely used non-invasive tests for the diagnosis and assessment of Crohn's disease (CD) activity. Despite this, factors other than disease activity which affect levels have not been extensively reviewed. This is of importance when using FC in the diagnostic setting but also may be of utility in studying the aetiology of disease.OBJECTIVES:Our review outlines environmental risk factors that affect FC levels influencing diagnostic accuracy and how these may be associated with risk of developing CD. FC as a surrogate marker could be used to validate risk factors established in case control studies where prospective studies are not feasible. Proof of this concept is provided by our identification of obesity as being associated with elevated FC, our subsequent confirmation of obesity as risk factor for CD and the subsequent verification in prospective studies, as well as associations of lack of physical activity and dietary fibre intake with elevated FC levels and their subsequent confirmation as risk factors in prospective studies.CONCLUSION:We believe that FC is likely to prove a useful surrogate marker for risk of developing CD. This review has given a theoretical basis for considering the epidemiological determinants of CD which to date has been missing.

Background: Artesunate is an antimalarial agent with broad anti-cancer activity in in vitro and animal experiments and case reports. Artesunate has not been studied in rigorous clinical trials for anticancer effects. Aim: To determine the anticancer effect and tolerability of oral artesunate in colorectal cancer (CRC). Methods: This was a single centre, randomised, double-blind, placebo-controlled trial. Patients planned for curative resection of biopsy confirmed single primary site CRC were randomised (n = 23) by computer-generated code supplied in opaque envelopes to receive preoperatively either 14 daily doses of oral artesunate (200 mg; n = 12) or placebo (n = 11). The primary outcome measure was the proportion of tumour cells undergoing apoptosis (significant if >7% showed Tunel staining). Secondary immunohistochemical outcomes assessed these tumour markers: VEGF, EGFR, c-MYC, CD31, Ki67 and p53, and clinical responses. Findings: 20 patients (artesunate = 9, placebo = 11) completed the trial per protocol. Randomization groups were comparable clinically and for tumour characteristics. Apoptosis in >7% of cells was seen in 67% and 55% of patients in artesunate and placebo groups, respectively. Using Bayesian analysis, the probabilities of an artesunate treatment effect reducing Ki67 and increasing CD31 expression were 0.89 and 0.79, respectively. During a median follow up of 42 months 1 patient in the artesunate and 6 patients in the placebo group developed recurrent CRC. Interpretation: Artesunate has anti-proliferative properties in CRC and is generally well tolerated.

Introduction Third and fourth degree perineal tears will occur in a small proportion of vaginal deliveries. When found at the time of delivery, they are typically repaired primarily. Patients may subsequently suffer from faecal incontinence. Method All patients with a third and fourth degree tear were referred for assessment. This included endoanal ultrasonography and estimation of incontinence with the Cleveland Clinic faecal incontinence score. Data from 2001 to 2013 were analysed. Results 888 patients were included. Of these, 551 (62%) were found to have a sphincter defect. 333 (38%) had intact sphincters. The majority of these had normal looking sphincters on ultrasonography. The mean (SD) incontinence score for those with a defect was 4.3 (5.5). The mean incontinence score for those with no defect was 4.2 (5.8). Conclusion The majority of patients had a sphincter defect. This suggests that there is a high failure rate from the primary repair. The high proportion of normal looking sphincters suggests that third and fourth degree tears may be over diagnosed. Despite the ultrasound findings, the incontinence scores for both groups were comparable. Disclosure of interest None Declared.

Artesunate, a semi-synthetic and water-soluble artemisinin-derivative used as an anti-malarial agent, has attracted the attention of cancer researchers due to a broad range of anti-cancer activity including anti-angiogenic, immunomodulatory and treatment-sensitisation effects. In addition to pre-clinical evidence in a range of cancers, a recently completed randomised blinded trial in colorectal cancer has provided a positive signal for further clinical investigation. Used perioperatively artesunate appears to reduce the rate of disease recurrence - and the Neo-Art trial, a larger Phase II RCT, is seeking to confirm this positive effect. However, artesunate is a generic medication, and as with other trials of repurposed drugs, the Neo-Art trial does not have commercial sponsorship. In an innovative move, the trial is seeking funds directly from members of the public via a crowd-funding strategy that may have resonance beyond this single trial.

Much has been written about the role of diet and risk for Crohn's disease (CD). However, the evidence is contradictory. Recent evidence has pointed to fiber playing an important role along with the possibility that dietary fat and overnutrition also have a role. Diet has a clearer place in disease modification, with some diets used in the treatment of CD. The lack of clarity stems from a poor understanding of the mechanisms underlying the relationship between diet and CD. Gut permeability is likely to play a key role in the risk for CD. Mechanisms whereby diet can affect gut permeability, including the effects of the gut microbiota, are reviewed. Modification of disease behavior is likely to be influenced by additional mechanisms, including recognition of complex food antigens. As with many other chronic diseases, a surrogate marker of CD risk would greatly aid evaluation of the dietary factors involved. Formal measures of gut permeability are too cumbersome for large-scale use, but fecal calprotectin may be a convenient measure of this. There are only preliminary data on the effect of diet and microbiota composition on fecal calprotectin and these require further investigation.

Introduction . Resection and strictureplasty are used to treat patients with obstructive Crohn’s disease. Strictureplasty is preferable in adults as it retains bowel length. This study aims to identify differences in outcomes of children undergoing strictureplasty and resection for obstructive Crohn’s disease. Method. Patients under 20 years undergoing surgery over a nine-year period were included. Data was collected on procedures for stenotic Crohn’s disease. Patients were divided into 2 groups: Group 1 treated with strictureplasties and Group 2 resections. Postoperative complications and recurrence rates were recorded. Kaplan-Meier method was used to analyze the data. Results . Twenty-six patients and 40 operations were identified. Mean age was 15.6 years (7.2–19.4) with equal numbers of males and females. Mean follow-up was 45.9 months (0.1–149.9). 20/40 procedures involved the terminal ileum; 9/40, the ileocolic junction; 8/40, the upper GI tract; and 3/40, the colon. Group 1 consisted of 19 strictureplasties and Group 2 consisted of 13 resections and 8 combined procedures. Significantly more patients in Group 1 required further surgery (11/19 versus 3/21;P=0.008). Conclusion . Allowing for variations in disease duration, severity, and previous medical management, these data suggest that resection is preferable to strictureplasty in treating obstructive Crohn’s disease in children and adolescents.

Introduction Colorectal cancer (CRC) progression is associated with suppression of host cell mediated immunity (CMI) and local immune escape mechanisms (1.2). The aim of the study was to assess immune function in terms of the DNA methylation and expression of TNF, IFN- γ and FOXP3 and to identify potential targets for immunotherapy in CRC. Methods 60 CRC patients and 15 matched controls were recruited. TaqMan quantitative PCR (qRT-PCR) was performed for relative quantitation of expression of TNF, IFNG, FOXP3 in the PBMC and tumour. Methylation specific PCR was performed to determine the methylation status. MSI status was determined using microsatellite primers BAT25 and BAT26. Results TNF expression was suppressed in CRC tumours (median fold change 0.48). IFN- γ was found to be suppressed in the PBMC (median 0.34) of CRC patients. Tumours showed enhanced expression of FOXP3 (median 2.2). Expression of FOXP3 in tumours was significantly higher when the size of the tumour was more than 50mm (p = 0.005). Methylated TNFpromoter and FOXP3cpg correlated significantly with suppression of TNF and FOXP3 respectively. Significant TNF suppression (p = 0.002) was noted in the PBMC of patients with MSI. No correlation was observed between the MSI status and DNA methylation status of our study genes. Conclusion Our study identified changes in protein expression which correlated with the methylation status. It demonstrates the influence of DNA methylation on gene expression that could act as a biomarker for future immunotherapy with possible role for demethylating agents. Disclosure of Interest None Declared. References Heriot AG, Marriott JB, Cookson S, Kumar D, Dalgleish AG. Reduction in cytokine production in colorectal cancer patients: association with stage and reversal by resection. Br J Cancer 2000; 82(5): 1009–1012. Galizia G, Lieto E, De Vita F, Romano C, Orditura M, Castellano P, Imperatore V, Infusino S, Catalano G, Pignatelli C. Circulating levels of interleukin-10 and interleukin-6 in gastric and colon cancer patients before and after surgery: relationship with radicality and outcome. J Interferon Cytokine Res 2002; 22(4): 473–482.

Introduction The bowel cancer screening programme (BCSP) is known to detect majority of colorectal cancer (CRC) at an earlier stage. We aimed at determining the outcome of screen detected CRC (SDCRC). Methods 165 patients diagnosed with CRC through BCSP were compared to a control group, which included 179 age matched patients diagnosed with CRC before the implementation of BCSP. Survival analysis was performed at a median follow up of 36 months. Results The SDCRC and control groups were similar with respect to gender distribution and vascular invasion (VI). SDCRC were more likely to be detected at an earlier Modified Dukes’ stage (p < 0.001). The stage distribution of SDCRC was similar to the national pilot (1) except for a higher percentage with metastatic disease (9% v 1%). During the follow up of SDCRC, 23 patients developed recurrent CRC and 19 patients died. While the overall survival (OS) was significantly better in SDCRC (p < 0.001), the recurrence free survival (RFS) in SDCRC was similar to the control group (p = 0.798). Left sided tumours (p = 0.022, HR-5.3) and VI (p = 0.004, HR-8.3) had an independent adverse influence on RFS in SDCRC. VI had a significant influence on RFS in both polyp (p = 0.006) and non-polyp cancers (p = 0.012) among SDCRC. Conclusion While the OS was significantly better in the SDCRC, there was no significant difference in the RFS between the two groups. While the benefits of screening are clear, we need to be aware of the challenge posed by the expanding group of aggressive early CRC. Longer follow up is necessary to carefully quantify the survival and economic benefits achieved through NHS BCSP. Disclosure of Interest None Declared. Reference Results of the first round of a demonstration pilot of screening for colorectal cancer in the United Kingdom. BMJ 2004; 329:133.

Background Obesity and serum C-reactive protein (CRP) (a sensitive marker of inflammatory activity) are associated with most chronic diseases. Abdominal adiposity along with age is the strongest determinant of baseline CRP levels in healthy subjects. The mechanism of the association of serum CRP with disease is uncertain. We hypothesized that baseline serum CRP is a marker of inflammatory responsiveness to injury and that abdominal adiposity is the main determinant of this responsiveness. We studied the effect of abdominal adiposity, age and other environmental risk factors for chronic disease on the CRP response to a standardised surgical insult, unilateral hernia repair to not only test this hypothesis but to inform the factors which must be taken into account when assessing systemic inflammatory responses to surgery. Methods 102 male subjects aged 24-94 underwent unilateral hernia repair by a single operator. CRP was measured at 0, 6, 24 and 48 hrs. Response was defined as the peak CRP adjusted for baseline CRP. Results Age and waist:hip ratio (WHR) were associated both with basal CRP and CRP response with similar effect sizes after adjustment for a wide-range of covariates. The adjusted proportional difference in CRP response per 10% increase in WHR was 1.50 (1.17-1.91) p = 0.0014 and 1.15(1.00-1.31) p = 0.05 per decade increase in age. There was no evidence of important effects of other environmental cardiovascular risk factors on CRP response. Conclusion Waist:hip ratio and age need to be considered when studying the inflammatory response to surgery. The finding that age and waist:hip ratio influence baseline and post-operative CRP levels to a similar extent suggests that baseline CRP is a measure of inflammatory responsiveness to casual stimuli and that higher age and obesity modulate the generic excitability of the inflammatory system leading to both higher baseline CRP and higher CRP response to surgery. The mechanism for the association of baseline CRP and waist:hip ratio to chronic disease outcomes could be through this increase in inflammatory system excitability.

Extended abstract of a paper presented at Microscopy and Microanalysis 2012 in Phoenix, Arizona, USA, July 29 – August 2, 2012.

and endoscopic remission after two Phase 3 studies or an Open Label study with B-MMX 9 mg.Clinical and endoscopic remission was strictly defined as clinical and endoscopic remission (UCDAI score ≤1 after 8 weeks with no rectal bleeding (RB=0) and normal stool frequency (SF=0) and no mucosal friability at full colonoscopy and >1 point reduction from baseline endoscopic score).Patients were randomized (1:1) to B-MMX 6mg QD or PBO.For this extended use therapy, the maintenance of clinical remission was defined as RB= 0 and SF= 0. All patients who received at least one dose of B-MMX 6 mg or PBO were included in the safety analysis.Safety assessment was conducted at baseline, 1, 3, 6, 9, 12 months of treatment and/or End of Study/Early Withdrawal Visit.Results: Safety analysis included 123 patients.Potential glucocorticoid effects occurred at similar rates between treatment groups.Treatment-related AEs [B-MMX 6 mg (21.0%) and PBO (21.3%)] were similar between groups.(Table ) Mean morning cortisol levels remained within the normal range for all treatment visits.SAEs were infrequently reported [one patient (1.6%) in each group] and none were related to study drug.There were no deaths or life-threatening events during the study.Conclusion: In this extended use study, the rates of potential glucocorticoid effects, TEAEs, and TREAs were similar to PBO for long term maintenance of remission therapy.B-MMX 6 mg administered once daily for up to 12 months was well tolerated in patients with UC and with a comparable safety profile to PBO.