Reporting Pancreatic FNAC using the Papanicolaou System: Still a Diagnostic Challenge.

Introduction: The Papanicolaou Society of Cytopathology System for reporting Pancreaticobiliary Cytology (PSCPC) is a reliable method to classify pancreatic fine needle aspiration cytology (FNAC) smears. However, it is not without practical problems which can diminish the diagnostic accuracy of the cytological diagnosis. Aims and Objectives: To determine the diagnostic pitfalls while reporting cytomorphology of pancreatic lesions according to PSCPC on correlating FNAC findings with histopathology. Materials and Methods: Retrospective analysis of pancreatic FNAC smears received in the Department of Pathology of our tertiary care institute over a period of 2 years was done. The cytological diagnoses were classified according to the Papanicolaou Society of Cytopathology system of reporting pancreaticobiliary cytology and correlated with histopathology. The reasons of cyto-histological discordance were analyzed. Results: Out of 50 cases in which both FNAC and biopsy of pancreatic lesions were done, 34 cases were positive/malignant (Category VI), eight cases were suspicious for malignancy (Category V), three cases were neoplastic (Category IV), two cases were atypical (Category III), two cases were negative for malignancy (Category II), and one case was non-diagnostic (Category I). Out of 50 cases, histopathology was non-diagnostic due to inadequate material in six cases. The cytological diagnoses were compared with histopathology in the remaining 44 cases. Categories III, IV V, and VI were considered as positive for neoplastic pathology. The sensitivity of FNAC to predict neoplastic pathology was 97.5%, while the specificity was 25%. The positive predictive value was 92.9%. Two cases reported as atypical (Category III) turned out to be adenocarcinoma on histopathology. One case reported as neuroendocrine tumor and two cases reported as adenocarcinoma on cytology displayed features of chronic pancreatitis on histology. One case reported as neoplastic mucinous cyst (Category IV) turned out to be adenocarcinoma on histology (limited concordance). Conclusion: The cytopathologist needs to be wary of the potential pitfalls to improve the diagnostic accuracy of FNACs.

Burden of Anxiety, Depression and Perceived Stress in Patients with Inflammatory Bowel Disease: A Cohort Study from North India.

BACKGROUND: Patients with Inflammatory bowel disease (IBD) are susceptible to psychiatric co-morbidities. We aimed to ascertain the burden of anxiety, depression, and perceived stress in patients with IBD from north India. METHODS: Consenting adult patients with an established diagnosis of IBD were enrolled. The enrolled patients filled the Hospital Anxiety and Depression Scale (HADS) and Perceived Stress Scale (PSS) questionnaires. The patient and disease characteristics were analyzed to determine the correlations and predictors of psychiatric comorbidities. RESULTS: A total of 318 patients (255 UC, 63 CD; mean age 40.13 ± 12.06 years, 168 [52.8%] males; mean partial Mayo score 2.10 ± 2.35; and mean HBI 2.77 ± 2.13) were enrolled. The prevalence of anxiety, depression and moderate to high perceived stress was 14%, 12%, and 41%, respectively. Females had higher mean perceived stress, anxiety and depression scores compared to males. The partial Mayo score (PMS) correlated poorly with anxiety (ρ = 0.083, p = 0.187), depression (ρ = 0.123, p = 0.49) and perceived stress (ρ = 0.169; p = 0.007). The Harvey Bradshaw index (HBI) correlated fairly with anxiety (ρ = 0.336, p = 0.007) and poorly with depression (ρ = 0.287, p = 0.022) and perceived stress (ρ = 0.20; p = 0.117). Younger age (OR 0.93, 95% CI 0.90-0.97; p = 0.001) and hand-grip strength (OR 4.63, 95% CI 1.88-11.42; p = 0.001) predicted anxiety in patients with UC while rural area of residence (OR 4.75, 95% CI 1.03-21.98; p = 0.046) and HBI (OR 1.60, 95% CI 1.12-2.29; p = 0.009) were significant predictors of anxiety in patients with CD. CONCLUSION: Psychiatric comorbidities are common in patients with IBD, with higher prevalence in females. Young adults with UC and sarcopenia; and individuals with active CD living in rural areas are at an increased risk of anxiety.

Clinical and magnetic resonance imaging spectrum of complex perianal fistulizing Crohn's disease: A cohort study from northern India.

BACKGROUND: Fistulizing perianal Crohn's disease (CD) is a debilitating condition associated with significant morbidity and reduction in the quality of life. Magnetic resonance imaging (MRI) of the pelvis is the preferred imaging modality for the comprehensive assessment of the perianal fistula. There is a paucity of data from India on the MRI spectrum of complex perianal fistula in CD. METHODS: A single-centre cross-sectional analysis of patients with fistulizing perianal CD, who underwent pelvic MRI between January 2020 and December 2021, was performed. The clinical (age, sex, disease duration, disease location and behavior, disease activity [Perianal Disease Activity Index, PDAI] and treatment received) and radiological (number and location of fistulae, extensions, number and location of internal and external openings, fistula activity, presence or absence of perianal abscess and associated proctitis) characteristics of complex perianal fistula (defined according to the American Gastroenterological Association classification) were recorded. RESULTS: Of total 175 patients with CD who attended the gastroenterology clinic during the study period, 27 (15.42%) (mean age 42±15.5 years, 62.96% females and median disease duration four years) had complex perianal fistula and were included in the analysis. The mean PDAI was 5.48±2.53. The median Van Assche Index was 17 (interquartile range [IQR] 13-19). A majority (96.29%) of the fistulae were trans-sphincteric and four (14.81%) fistulae extended into the supralevator space. All fistulae were active on MRI. Concomitant perianal abscess and proctitis were seen in 59.26% (n=16) and 62.96% (n=17) of patients, respectively. Combination therapy with biologics and antibiotics/immune-suppressants were the most commonly prescribed medical therapy. Six (22.22%) patients underwent combined medical and surgical (non-cutting seton, fistulectomy, fecal diversion) treatment. CONCLUSION: The cumulative risk of the development of fistulizing perianal CD in a northern Indian cohort was similar to the western populations. Complex perianal fistulae were predominantly trans-sphincteric and commoner in females. MRI evaluation is pivotal for the delineation of fistula anatomy, assessment of disease extent and activity and the evaluation of concomitant perianal abscess and other complications.

Low prevalence of primary sclerosing cholangitis in patients with inflammatory bowel disease in India.

BACKGROUND/AIMS: Primary sclerosing cholangitis (PSC) represents the most common hepatobiliary extraintestinal manifestation of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD). Limited data exist on PSC in patients with IBD from India. We aimed to assess the prevalence and disease spectrum of PSC in Indian patients with IBD. METHODS: Database of IBD patients at 5 tertiary care IBD centers in India were analyzed retrospectively. Data were extracted and the prevalence of PSC-IBD was calculated. RESULTS: Forty-eight patients out of 12,216 patients with IBD (9,231 UC, 2,939 CD, and 46 IBD unclassified) were identified to have PSC, resulting in a prevalence of 0.39%. The UC to CD ratio was 7:1. Male sex and pancolitis (UC) or colonic CD were more commonly associated with PSC-IBD. The diagnosis of IBD preceded the diagnosis of PSC in most of the patients. Majority of the patients were symptomatic for liver disease at diagnosis. Eight patients (16.66%) developed cirrhosis, 5 patients (10.41%), all UC, developed malignancies (3 colorectal cancer [6.25%] and 2 cholangiocarcinoma [4.16%]), and 3 patients died (2 decompensated liver disease [4.16%] and 1 cholangiocarcinoma [2.08%]) on follow-up. None of the patients mandated surgical therapy for IBD. CONCLUSIONS: Concomitant PSC in patients with IBD is uncommon in India and is associated with lower rates of development of malignancies.

Evaluation of Nutritional Characteristics Reveals Similar Prevalence of Malnutrition in Patients with Ulcerative Colitis and Crohn's Disease.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with an increased risk of malnutrition and sarcopenia. AIMS: To evaluate the nutritional status of patients with IBD and determine the threshold values of different parameters of nutritional assessment to identify malnutrition. METHODS: This was a single-centre cross-sectional analysis of adult patients with IBD [ulcerative colitis (UC) and Crohn's disease (CD)] who underwent anthropometry [body mass index (BMI), mid upper arm circumference (MUAC) and triceps-fold thickness (TSF)], body composition analysis and assessment for sarcopenia [hand-grip strength and skeletal muscle index (SMI) at L3 vertebral level)]. Age- and gender-matched healthy adults served as controls. Malnutrition was defined according to the European Society of Clinical Nutrition and Metabolism (ESPEN) criteria. RESULTS: A total of 406 patients [336 (82.76%) UC and 70 (17.24%) CD; mean age 40.56 ± 13.67 years; 215 (52.95%) males] with IBD and 100 healthy controls (mean age 38.69 ± 10.90 years; 56 (56%) males) were enrolled. The mean BMI, MUAC, TSF thickness, fat and lean mass, hand-grip strength, and SMI at L3 vertebral level were lower in patients with IBD compared to controls. The prevalence of malnutrition was similar in UC and CD [24.40% (n = 82) and 28.57% (n = 20), respectively (p = 0.46)]. Thresholds for fat mass in females (15.8 kg) and visceral fat index in males (0.26) were both sensitive and specific to detect malnutrition. The cutoff values of MUAC and TSF thickness to identify malnutrition were 23.25 cm and 25.25 cm, and 16.50 mm and 8.50 mm, in females and males, respectively. CONCLUSION: Malnutrition and sarcopenia were common in patients with IBD, with the prevalence being similar in patients with both UC and CD.

(Re)Appraising Remission in Ulcerative Colitis.

As the therapeutic targets in ulcerative colitis (UC) shift from control of symptoms to mucosal healing and prevention of disease complications like disability, colectomy, and cancer, the definition of remission has evolved. The current definition of clinical remission is variable and is determined by the clinical context in which it is being used. This results in skepticism and uncertainty about the true meaning of the term "clinical remission." In this review, the authors reexamine the definition of clinical remission and propose a novel approach to define remission in UC.

The current definition of clinical remission in ulcerative colitis (UC) is variable and is determined by the clinical context in which it is being used. In this review, the authors reexamine the definition of clinical remission in UC and propose a novel approach to define remission based on the parameter being assessed.

Clinical spectrum of elderly-onset inflammatory bowel disease in India.

BACKGROUND/AIMS: Inflammatory bowel disease (IBD) is increasingly being recognized in elderly patients. Data on clinical spectrum of elderly-onset IBD patients is lacking from India. METHODS: A cross-sectional retrospective analysis of a prospectively maintained database of patients diagnosed with IBD was conducted at 2 centers in India. The clinical spectrum of elderly-onset IBD including demographic profile (age and sex), clinical presentation, disease characteristics (disease behavior and severity, extent of disease), and treatment were recorded and compared with adult-onset IBD. RESULTS: During the study period, 3,922 (3,172 ulcerative colitis [UC] and 750 Crohn's disease [CD]) patients with IBD were recorded in the database. A total of 186 patients (4.74%; 116 males [62.36%]) had elderly-onset IBD (69.35% UC and 30.64% CD). Diarrhea, blood in stools, nocturnal frequency and pain abdomen were the commonest presentations for UC, whereas pain abdomen, weight loss and diarrhea were the most frequent symptoms in CD. For both elderly onset UC and CD, majority of the patients had moderately severe disease. Left-sided colitis was the commonest disease location in UC. Isolated ileal disease and inflammatory behavior were the most common disease location and behavior, respectively in CD. 5-Aminosalicylates were the commonest prescribed drug for both elderly onset UC and CD. Thiopurines and biologics were used infrequently. Prevalence of colorectal cancer was higher in elderly onset IBD. CONCLUSIONS: Elderly onset IBD is not uncommon in India. Both the elderly onset UC and CD were milder, with no significant differences in disease characteristics (disease extent, location and behavior) when compared to adult-onset IBD. Colorectal cancer was more common in elderly onset IBD.

Correlation between magnetic resonance enterography and ileo-colonoscopy for assessment of disease activity in terminal ileal Crohn's disease.

BACKGROUND: Magnetic resonance enterography (MRE) has emerged as a novel tool for the assessment of disease activity in Crohn's disease (CD). Real world data from Indian subcontinent on performance of MRE in terminal ileal CD are lacking. METHODS: Retrospective analysis of patients with terminal ileal CD who underwent both ileo-colonoscopy and MRE was performed. Ileo-colonoscopy was considered the gold standard for assessment of disease activity. On ileo-colonoscopy, a simple endoscopic score for Crohn's disease (SES-CD) ≥2 was considered active disease; presence of ulcers indicated severe disease. MRE scoring of the disease activity was performed using magnetic resonance index of activity (MARIA) and simplified MARIA (MARIAs). The measure of agreement between ileo-colonoscopy and MRE and comparison of MARIA and MARIAs for assessment of disease activity and sensitivity of MRE to detect mucosal ulcerations were calculated. RESULTS: Seventy patients with terminal ileal CD (mean age 40.74±15.56 years; 71.4% males [n=50]) were evaluated. The sensitivities of MARIA and MARIAs scores to detect active disease were 0.76 and 0.84, respectively. The area under the receiver operating characteristic curve (AUROC) for detecting severe disease was 0.836 (p<0.0001) for MARIA and 0.861 (p<0.0001) for MARIAs. For mild active disease, there was no agreement between SES-CD and MARIA or MARIAs; however, for severe disease, the agreement was fair and moderate for MARIA and MARIAs, respectively. MARIA and MARIAs were comparable for identification of active and severe disease (κ 0.759, p<0.0001 and κ 0.840, p<0.0001, respectively). MRE was 68.18% sensitive to detect mucosal ulcers. CONCLUSION: MRE is a reliable and sensitive tool for detection of endoscopically severe, but not mild, terminal ileal CD.

Early fecal microbiome transfer after donor defecation determines response in patients with moderate to severe ulcerative colitis.

BACKGROUND: Fecal microbiome transfer (FMT) targeting gut microbiome dysbiosis is an emerging therapy for ulcerative colitis (UC). There is however no consensus on protocols for performing FMT in UC, especially in relation to time after donor feces defecation. METHODS: This is a single-center retrospective analysis of patients with moderate-severe UC (total Mayo Clinic score ≥6 and endoscopic Mayo Clinic subscore of ≥2) treated with FMT between September 2017 and December 2019 at Dayanand Medical College and Hospital, Ludhiana, India. Fresh fecal samples from unrelated healthy voluntary donors were administered through colonoscopy at weeks 0, 2, 6, 10, 14, 18, and 22. Time interval between donor feces defecation and FMT procedure was recorded for each FMT session and the mean time of seven sessions was designated aika. Impact of aika on clinical response and safety of FMT was evaluated. RESULTS: During the study period, 123 adult patients (mean age 33.75±11.97 years, 61.8% [n=76] males) with moderate-severe UC (mean total Mayo Clinic and endoscopic Mayo Clinic scores 7.49±1.60 and 2.50±0.50, respectively) were treated with FMT. The mean aika was 2.29±0.75 h. The aika was smaller in patients who responded to FMT as compared to non-responders (2.13±0.75 h vs. 2.71±0.76 h, p=0.0002) as well as in patients achieving clinical remission (2.15±0.76 h vs. 2.42±0.76 h, p=0.05). There was no significant impact of aika on adverse effects except for the incidence of borborygmi after FMT, which was higher in patients with aika ≤2 h. CONCLUSION: Early FMT after donor feces defecation favorably impacts the clinical response rates in patients with active UC.

Endoscopy for assessment of mucosal healing in ulcerative colitis: time bound or response guided?

The timing of colonoscopy in patients with active ulcerative colitis (UC) lacks coherence. The published guidelines and recommendations advocate time-bound colonoscopy in patients with active UC to assess for mucosal healing. However, the practice of performing colonoscopies at fixed time frames lacks reasoning. The time to achieve mucosal healing in UC is not uniform across the patient populations and is influenced by the disease severity and efficacy and time to therapeutic response of the drugs being used. Additionally, with the availability of sensitive noninvasive inflammatory biomarkers such as fecal calprotectin, that parallel the disease activity and correlate with mucosal healing, the notion of performing colonoscopy at fixed intervals sounds unjustifiable. The authors express their view that a response-guided colonoscopy (driven by normalization of clinical symptoms and inflammatory biomarkers), rather than a time-bound colonoscopy, would be more logical, apart from being cost-effective and patient-friendly.

Use of thiopurines in inflammatory bowel disease: an update.

Inflammatory bowel disease (IBD), once considered a disease of the Western hemisphere, has emerged as a global disease. As the disease prevalence is on a steady rise, management of IBD has come under the spotlight. 5-Aminosalicylates, corticosteroids, immunosuppressive agents and biologics are the backbone of treatment of IBD. With the advent of biologics and small molecules, the need for surgery and hospitalization has decreased. However, economic viability and acceptability is an important determinant of local prescription patterns. Nearly one-third of the patients in West receive biologics as the first/initial therapy. The scenario is different in developing countries where biologics are used only in a small proportion of patients with IBD. Increased risk of reactivation of tuberculosis and high cost of the therapy are limitations to their use. Thiopurines hence become critical for optimal management of patients with IBD in these regions. However, approximately one-third of patients are intolerant or develop adverse effects with their use. This has led to suboptimal use of thiopurines in clinical practice. This review article discusses the clinical aspects of thiopurine use in patients with IBD with the aim of optimizing their use to full therapeutic potential.

Peritoneal malignant mesothelioma: Slippery like an eel to diagnose on cytology-case series of 3 cases.

INTRODUCTION: Peritoneal malignant mesothelioma is an extremely rare tumor and is a difficult diagnosis to be made on cytology alone. We report 3 cases where the cytologic features were misdiagnosed as carcinoma/lymphoma but histopathology and immunohistochemistry (IHC) established the diagnosis of malignant mesothelioma. CLINICAL DETAILS: Case 1 was a 60-year-old man with multiloculated ascites and omental caking. Peritoneal fluid was reported as malignant on cytology but was misclassified as adenocarcinoma. Case 2, a 45-year-old man with ascites and peritoneal nodularity, radiologically mimicking peritoneal carcinomatosis, was also reported positive for malignancy on ascitic fluid cytology. Fine-needle aspiration (FNAC) from omental fat revealed signet ring cells, thus misleading to cytologic diagnosis of adenocarcinoma. Case 3 was a 63-year-old man with perisplenic mass with extensive omental caking and peritoneal nodularity that was also suspected to be peritoneal carcinomatosis on radiology. FNAC smears from perisplenic mass showed sheets of plasmacytoid cells. On cytology, the differential diagnoses offered were neuroendocrine tumor or non-Hodgkin lymphoma. The diagnosis of malignant mesothelioma was established only after IHC on histopathologic sections in all these cases. None of our patients had history of prior asbestos exposure. CONCLUSION: In such clinical scenarios, with radiology suggesting peritoneal carcinomatosis, the cytologic features need corroboration by IHC/fluorescence in situ hybridization on cell block or biopsy to correctly identify malignant mesothelioma and differentiate it from metastatic carcinomatous deposits and benign mesothelial proliferation.

Trends of inflammatory bowel disease at a tertiary care center in northern India.

BACKGROUND/AIMS: Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is increasingly being reported from India and other Asian countries. This study looks into the changing trends of IBD at a tertiary care center in north India over last two decades. METHODS: Retrospective analysis of a prospectively maintained database of patients diagnosed with IBD between January 1991 and December 2015 was conducted. The study period was divided into five times cohorts (1991-1995, 1996-2000, 2001-2005, 2006-2010, 2011-2015). RESULTS: During the study period, 2,467 patients (UC [n = 2,137, 86.6%], CD [n = 330, 13.3%], mean age 38.5 ± 13.3 years; 55.9% males) were registered. The proportion of patients with CD increased (ratio of UC to CD declined from 15.7:1 to 4:1). The mean age at diagnosis decreased for UC (45.7 ± 12.1 years in 1991-1995 vs. 37.6 ± 13.0 years in 2011-2015; P= 0.001) and remained consistent for CD (41.3 ± 13.6 years in 1996-2000 vs. 41.3 ± 16.9 years in 2011-2015, P= 0.86). Patients with proctitis in UC and isolated ileal disease in CD increased over the study period (P= 0.001 and P= 0.007, respectively). Inflammatory CD increased (P= 0.009) whereas stricturing CD decreased (P= 0.01) across all cohorts. There was a trend towards less severe presentation of both UC and CD. The use of thiopurines (P= 0.02) and biologics increased (P= 0.001) with no significant change in trends for requirements of surgery (P= 0.9). CONCLUSIONS: Increasing prevalence of CD, younger age at diagnosis, diagnosis at an earlier and milder stage, greater use of thiopurines and biologics were observed.

Colitis and Crohn's Foundation (India): a first nationwide inflammatory bowel disease registry.

BACKGROUND/AIMS: The national registry for inflammatory bowel disease (IBD) was designed to study epidemiology and prescribing pattern of treatment of IBD in India. METHODS: A multicenter, cross-sectional, prospective registry was established across four geographical zones of India. Adult patients with ulcerative colitis (UC) or Crohn's disease (CD) were enrolled between January 2014 and December 2015. Information related to demographics; disease features; complications; and treatment history were collected and analyzed. RESULTS: A total of 3,863 patients (mean age, 36.7 ± 13.6 years; 3,232 UC [83.7%] and 631 CD [16.3%]) were enrolled. The majority of patients with UC (n = 1,870, 57.9%) were from north, CD was more common in south (n = 348, 55.5%). The UC:CD ratio was 5.1:1. There was a male predominance (male:female = 1.6:1). The commonest presentation of UC was moderately severe (n = 1,939, 60%) and E2 disease (n = 1,895, 58.6%). Patients with CD most commonly presented with ileocolonic (n = 229, 36.3%) inflammatory (n = 504, 79.9%) disease. Extraintestinal manifestations were recorded among 13% and 20% of patients in UC and CD respectively. Less than 1% patients from both cohorts developed colon cancer (n = 26, 0.7%). The commonly used drugs were 5-aminosalicylates (99%) in both UC and CD followed by azathioprine (34.4%). Biologics were used in only 1.5% of patients; more commonly for UC in north and CD in south. CONCLUSIONS: The national IBD registry brings out diversities in the 4 geographical zones of India. This will help in aiding research on IBD and improving quality of patient care.

Clinical Predictors of response to Faecal Microbiota Transplantation in patients with active ulcerative colitis.

BACKGROUND: Fecal Microbiota Transplantation (FMT) has been shown to be effective for induction of remission in patients with active ulcerative colitis (UC). At present, clinical factors impacting the response to FMT in UC remain unclear. METHODS: Patients with active UC treated with multisession FMT via colonoscopy at weeks 0, 2, 6, 10, 14, 18, and 22, were analysed. Response to FMT was defined as achievement of corticosteroid free clinical remission at week 30. Patient and disease characteristics were evaluated to determine the predictors of response to FMT. RESULTS: Out of 140 patients with active UC treated with FMT, 93 patients [mean age 34.96±11.27 years, 62.36% males (n=58), mean Mayo clinic score 8.07±2.00] who completed the multi-session FMT protocol were analysed. Fifty-seven (61.29%) patients achieved clinical remission. Younger age (OR for age 0.93, 95% CI 0.89-0.97, p=0.001), moderate (Mayo clinic score 6-9) disease severity (OR 3.01, 95% CI 1.12 to 8.06, p=0.025) and endoscopic Mayo score 2 (OR 5.55, 95% CI 2.18-14.06, p<0.001) were significant predictors of remission on univariate analysis. Younger age, disease extent E2 and endoscopic mayo score 2 (OR 0.925, 95% CI 0.88-0.97, p=0.002; OR 2.89, 95% CI 1.01-8.25, p=0.04 and OR 8.43, 95% CI 2.38-29.84, p=0.001, respectively) were associated with clinical remission on multivariate logistic regression. A mathematical model (nomogram) was developed for estimating the probability of remission with FMT protocol. CONCLUSION: Younger age, disease extent E2, and endoscopic mayo score 2 significantly predict achievement of clinical remission with FMT in active UC. The prediction model can help in selecting individuals for FMT. Validation in larger cohorts is needed.

Exclusive enteral nutrition for induction of remission in anti-tumor necrosis factor refractory adult Crohn's disease: the Indian experience.

BACKGROUND/AIMS: Exclusive enteral nutrition (EEN) is recommended for induction of remission in pediatric Crohn's disease (CD). However, it is not currently recommended for inducing remission in adults. This report describes the use of 12-week EEN for induction of remission in anti-tumor necrosis factor (anti-TNF) refractory adult CD. METHODS: This is a retrospective analysis of adults with moderate to severe active (Crohn's Disease Activity Index [CDAI] >220) anti-TNF refractory CD, who received EEN for 12 weeks between April 2018 and March 2019 at Dayanand Medical College and Hospital, Ludhiana, India. Primary outcomes included achievement of clinical remission and fistula healing at 12 weeks. Improvement in inflammatory markers and nutritional status were the secondary end points. RESULTS: Out of 23 patients who received anti-TNF agents, 7 (30.4%) were refractory and were offered EEN as a salvage therapy. Six patients (66.7% females, mean age 25.6±6.5 years) consented. Four patients (66.6%) achieved clinical remission (CDAI <150). Mean CDAI of patients decreased significantly after 12 weeks of EEN (388.8±74.8 vs. 160.0±25.2, P<0.001). Perianal fistulas showed clinical response (drainage decreased by >50%), though none achieved remission. Entero-enteric fistulae showed complete healing. Mean body mass index improved from 15.6±3.1 to 18.9±1.9 kg/m2 at week 12 (P=0.003). Hemoglobin and serum albumin also improved from 8.2±1.1 g/dL and 2.8±0.3 g/dL at baseline to 12.6±0.6 g/dL and 3.6±0.5 g/dL post-EEN respectively (P<0.001 and P=0.006 respectively). CONCLUSIONS: EEN appears to be an effective and well tolerated therapy for induction of remission in anti-TNF refractory adult CD. More data from prospective trials with larger number of patients is required.

Acceptability, tolerability, and safety of fecal microbiota transplantation in patients with active ulcerative colitis (AT&S Study).

BACKGROUND AND AIM: Fecal microbiota transplantation (FMT) targets gut microbiome dysbiosis and is an emerging therapy for ulcerative colitis (UC). Although initial results with FMT in patients with active UC are encouraging, data regarding its acceptability, tolerability, and safety are scant. METHODS: A retrospective analysis of patients with active UC (Mayo clinic score ≥ 4), who received multisession FMT (at weeks 0, 2, 6, 10, 14, 18, and 22) via colonoscopy between June 2016 and June 2018, was performed. Patient acceptability, tolerability, and immediate and long-term safety of the therapy were assessed. RESULTS: Of the 129 patients with active UC who were offered FMT, 101 patients consented, giving acceptability of 78.3%. Fecal slurry retention time improved with each session (3.27 ± 1.06 h for the first session vs 5.12 ± 0.5 h for the seventh session). Abdominal discomfort, flatulence, abdominal distension, borborygmi, and low-grade fever (30.8%, 15.9%, 9.8%, 7.9%, and 7.6%, respectively) were the most common post-procedural short-term adverse events. Long-term adverse events included new-onset urticaria (n = 2, 4.3%), arthritis/arthralgia (n = 3, 6.5%), depression (n = 1, 2.2%), partial sensorineural hearing loss (n = 1, 2.2%), and allergic bronchitis (n = 1, 2.2%). Thirteen (12.9%) patients dropped out because of adverse events. CONCLUSION: Fecal microbiota transplantation appears to be a safe and well-tolerated procedure, with good acceptability in patients with active UC.

Diet and inflammatory bowel disease: The Asian Working Group guidelines.

INTRODUCTION: These Asian Working Group guidelines on diet in inflammatory bowel disease (IBD) present a multidisciplinary focus on clinical nutrition in IBD in Asian countries. METHODOLOGY: The guidelines are based on evidence from existing published literature; however, if objective data were lacking or inconclusive, expert opinion was considered. The conclusions and 38 recommendations have been subject to full peer review and a Delphi process in which uniformly positive responses (agree or strongly agree) were required. RESULTS: Diet has an important role in IBD pathogenesis, and an increase in the incidence of IBD in Asian countries has paralleled changes in the dietary patterns. The present consensus endeavors to address the following topics in relation to IBD: (i) role of diet in the pathogenesis; (ii) diet as a therapy; (iii) malnutrition and nutritional assessment of the patients; (iv) dietary recommendations; (v) nutritional rehabilitation; and (vi) nutrition in special situations like surgery, pregnancy, and lactation. CONCLUSIONS: Available objective data to guide nutritional support and primary nutritional therapy in IBD are presented as 38 recommendations.

Role of Faecal Microbiota Transplantation for Maintenance of Remission in Patients With Ulcerative Colitis: A Pilot Study.

OBJECTIVES: To study the role of faecal microbiota transplantation [FMT] in maintenance of remission in ulcerative colitis [UC]. METHODS: In this pilot study, patients with UC in clinical remission achieved after multi-session FMT were randomly allocated to either maintenance FMT or placebo colonoscopic infusion every 8 weeks, for 48 weeks. The standard of care [SOC] therapy was continued in all patients. The primary endpoint was maintenance of steroid-free clinical remission [Mayo score ≤2, all subscores ≤1] at Week 48. Secondary endpoints were achievement of endoscopic remission [endoscopic Mayo score 0] and histological remission [Nancy grade 0, 1] at Week 48. RESULTS: In all, 61 patients in clinical remission were randomised to receive either FMT [n = 31] or placebo [n = 30]. The primary outcome was achieved in 27/31 [87.1%] patients allocated FMT versus 20/30 [66.7%] patients assigned placebo [p = 0.111]. Secondary endpoints of endoscopic remission (FMT: 18/31 [58.1%] versus placebo: 8/30 [26.7%], p = 0.026) and histological remission (FMT: 14/31 [45.2%] versus placebo: 5/30 [16.7%], p = 0. 033) were achieved in a significantly higher number of patients with FMT. Three patients receiving FMT [9.7%] and 8 patients on placebo [26.7%] relapsed. There were no serious adverse events necessitating discontinuation in patients on FMT; one patient who relapsed on placebo required colectomy. CONCLUSIONS: Maintenance FMT in patients who are in clinical remission may help sustain clinical, endoscopic and histological remission in patients with UC.

Variable Immunogenic Potential of Wheat: Prospective for Selection of Innocuous Varieties for Celiac Disease Patients via in vitro Approach.

Celiac Disease (CD) is a multifactorial, autoimmune enteropathy activated by cereal proteins in genetically predisposed individuals carrying HLA DQ2/8 genes. A heterogenous gene combination of the cereal prolamins is documented in different wheat genotypes, which is suggestive of their variable immunogenic potential. In the current study, four wheat varieties (C591, C273, 9D, and K78) identified via in silico analysis were analyzed for immunogenicity by measuring T-cell proliferation rate and levels of inflammatory cytokines (Interferon-γ and Tumor Necrosis Factor-α). Peripheral Blood Mononuclear Cells and biopsy derived T-cell lines isolated from four CD patients in complete remission and two controls were stimulated and cultured in the presence of tissue transglutaminase activated pepsin-trypsin (PT) digest of total gliadin extract from test varieties. The immunogenicity was compared with PBW 621, one of the widely cultivated wheat varieties. Phytohaemagglutinin-p was taken as positive control, along with unstimulated cells as negative control. Rate of cell proliferation (0.318, 0.482; 0.369, 0.337), concentration of IFN- γ (107.4, 99.2; 117.9, 99.7 pg/ml), and TNF- α (453.8, 514.2; 463.8, 514.2 pg/ml) was minimum in cultures supplemented with wheat antigen from C273, when compared with other test varieties and unstimulated cells. Significant difference in toxicity levels among different wheat genotypes to stimulate celiac mucosal T-cells and PBMC's was observed; where C273 manifested least immunogenic response amongst the test varieties analyzed.