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.

Effectiveness of Tofacitinib in Ulcerative Proctitis Compared to Left Sided Colitis and Pancolitis.

BACKGROUND: Ulcerative proctitis (UP), though associated with high symptom burden and poor quality of life, is excluded from most of the randomized controlled trials in UC, including the OCTAVE trials. We aimed to analyse the effectiveness of tofacitinib in UP, and compare it to that in left sided colitis (LSC) and pancolitis (PC). METHODS: This was a prospective cohort study. Patients with either steroid-dependent or refractory ulcerative colitis, who received tofacitinib, were divided into three groups based on the disease extent [UP, LSC and PC]. The primary outcome was comparison of proportion of patients in clinical remission in the three groups, at weeks 8, 16 and 48. Safety outcomes were reported using incidence rate per patient year of exposure. RESULTS: Clinical remission was achieved in 47%(15/32), 24%(23/94), and 43%(23/54) of patients at week 8, 56%(18/32), 37%(35/94), and 56%(30/54) of patients at week 16, and 59%(19/32), 38%(36/94), and 24%(13/54) of patients at week 48 in groups UP, LSC and PC, respectively. Corticosteroid-free clinical remission rates were significantly higher in patients in groups UP at week 48. Five (15%) patients with UP were primary non-responders to tofacitinib at week 16, while three (9%) patients had secondary loss of response at week 48. The probability of sustained clinical response was highest in patients with UP. Patients with UP had the lowest incidence of adverse effects. CONCLUSION: The effectiveness of tofacitinib in inducing and maintaining clinical remission is greater in patients with UP compared to LSC and PC.

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.

Tofacitinib Versus Oral Prednisolone for Induction of Remission in Moderately Active Ulcerative Colitis [ORCHID]: A Prospective, Open-Label, Randomized, Pilot Study.

BACKGROUND: Oral corticosteroids are first-line agents to induce remission in moderately active ulcerative colitis [UC], but are associated with adverse effects. We compared the efficacy and safety of tofacitinib and prednisolone for induction of remission in moderately active UC. METHODS: This was a single-centre, prospective, open-label, randomized, active-controlled pilot study. Eligible patients [aged ≥18 years] had moderately active UC. Participants were randomly assigned to receive either prednisolone [40 mg daily, tapered by 5 mg every week] or tofacitinib [10 mg twice daily] for 8 weeks. The primary endpoint was composite remission [defined as total Mayo clinic score ≤2, with endoscopic sub-score of 0 and faecal calprotectin <100 µg/g] at 8 weeks. RESULTS: Seventy-eight patients were randomly assigned to either of the treatment groups. At week 8, the proportion of patients achieving composite remission in the tofacitinib [7/43, 16.28%] and prednisolone groups [3/35, 8.57%] were not significantly different (odds ratio [OR] 2.07, 95% confidence interval [CI] 0.49-8.70; p = 0.31). The time to achieve symptomatic remission [normal stool frequency with absence of rectal bleeding] was similar (10 days, interquartile range [IQR 7-18.75] and 10 days [IQR 5-12.5] for tofacitinib and prednisolone, respectively; p = 0.25) in the two groups. One patient each in the tofacitinib and prednisolone group discontinued treatment due to development of pulmonary tuberculosis and pustular acne, respectively. One patient receiving tofacitinib developed herpes zoster, but did not require cessation of therapy. No serious adverse events or major adverse cardiovascular events were observed. CONCLUSION: In patients with moderately active UC, there was no difference in the efficacy and safety of tofacitinib and oral prednisolone for induction of remission at 8 weeks. TRAIL REGISTRATION: Clinical Trials Registry of India [CTRI/2021/10/037641].

Trends of inflammatory bowel disease from the Global Burden of Disease Study (1990-2019).

BACKGROUND: The global burden of inflammatory bowel disease (IBD) is reportedly increasing. Methodologies and datasets are routinely updated, allowing for more accurate estimates to guide healthcare policy. METHODS: The Global Burden of Diseases, Injuries and Risk Factors Study (GBD) dataset was accessed and the trends in IBD at the global and regional levels from 1990 to 2019 were estimated for incidence, prevalence, deaths, years of life lost (YLL), years lived with disability (YLD) and disability-adjusted life-years (DALYs) per 100,000 population. The three decadal trends of the disease measures were calculated. RESULTS: In 2019, there were 4.9 million (95% Uncertainty Interval [UI] 4.3-5.5) cases of IBD globally. The age-standardized prevalence and incidence rates decreased from 73.23 (95% UI 63.8-83.6) and 6.1 (95% UI 5.3-6.9) in 1990 to 59.2 (95% UI 52.7-66.4) and 4.9 (95% UI 4.4-5.6) in 2019, respectively. Like prior estimates, the highest age-standardized prevalence and incidence rates occurred in North America, but the lowest rates were reported in Oceania (209.5 [195.4-224.4] and 24.5 [22.6-26.7] and 3.87 [3.1-4.7] and 0.5 [0.5-0.7], respectively) and not the Caribbean, as previously reported. High socio-demographic index (SDI) locations had the highest age-standardized prevalence rate, though the rates declined in 2019 compared to 1990. The age-standardized prevalence and incidence rates increased in middle, low middle and low SDI quintiles over the three decades. The age-standardized rates for deaths, DALYs, YLD and YLL decreased globally from 1990 to 2019. Between 1990 and 2019 the total number of patients with IBD in India doubled from 0.13 million (95% UI 0.10-0.16) to 0.27 million (95% UI 0.21-0.33) with age-standardized incidence rate increasing from 2.23 (95% UI 1.85-2.73) to 2.34 (95% UI 1.95-2.86). CONCLUSION: This analysis of the GBD 2019 database demonstrates that the overall global burden of IBD is lower than previously estimated, but an increasing disease burden is observed in the middle and low-SDI locations.

Tofacitinib in Acute Severe Ulcerative Colitis (TACOS): A Randomized Controlled Trial.

INTRODUCTION: Intravenous corticosteroids are the mainstay of treatment of patients hospitalized with acute severe ulcerative colitis (ASUC). However, 30%-40% of the patients are refractory to corticosteroids. We investigated whether addition of tofacitinib to corticosteroids improved the treatment responsiveness in patients with ASUC. METHODS: This single-center, double-blind, placebo-controlled trial randomized adult patients with ASUC (defined by the Truelove Witts severity criteria) to receive either tofacitinib (10 mg thrice daily) or a matching placebo for 7 days while continuing intravenous corticosteroids (hydrocortisone 100 mg every 6 hours). The primary end point was response to treatment (decline in the Lichtiger index by >3 points and an absolute score <10 for 2 consecutive days without the need for rescue therapy) by day 7. The key secondary outcome was the cumulative probability of requiring initiation of infliximab or undergoing colectomy within 90 days following randomization. All analyses were performed in the intention-to-treat population. RESULTS: A total of 104 patients were randomly assigned to a treatment group (53 to tofacitinib and 51 to placebo). At day 7, response to treatment was achieved in 44/53 (83.01%) patients receiving tofacitinib vs 30/51 (58.82%) patients receiving placebo (odds ratio 3.42, 95% confidence interval 1.37-8.48, P = 0.007). The need for rescue therapy by day 7 was lower in the tofacitinib arm (odds ratio 0.27, 95% confidence interval 0.09-0.78, P = 0.01). The cumulative probability of need for rescue therapy at day 90 was 0.13 in patients who received tofacitinib vs 0.38 in patients receiving placebo (log-rank P = 0.003). Most of the treatment-related adverse effects were mild. One patient, receiving tofacitinib, developed dural venous sinus thrombosis. DISCUSSION: In patients with ASUC, combination of tofacitinib and corticosteroids improved treatment responsiveness and decreased the need for rescue therapy.

Inflammatory Bowel Disease and X (Formerly Twitter) Influencers: Who Are They and What Do They Say?

Background and objective More than half of the population suffering from inflammatory bowel disease (IBD) use the internet as a primary source of information on their condition. X (formerly Twitter) has been increasingly used to disseminate healthcare-related information. In this study, we aimed to identify top influencers on the topic of IBD on X and correlate the relevance of their social media engagements with their professional expertise or academic productivity. Methods X (formerly Twitter) influence scores for the search topic IBD were obtained using Cronycle API, a proprietary software employing multiple algorithms to rank influencers. Data regarding gender, profession, location, and research productivity represented as h-index was collected. Results We collected information on the top 100 IBD influencers on X. The majority of influencers were gastroenterologists, followed by IBD advocates. Of note, 62% of the IBD influencers were from the US followed by the UK and Canada. A positive correlation was observed between the X topic score and the h-index of the influencer (r=+0.488, p<0.001) Conclusions The strong correlation observed between the X topic score and h-index suggests that social media is a viable platform for gaining information regarding IBD. Further research aimed at counteracting misleading information by providing facts and data in a succinct manner about IBD on social media is required to improve disease awareness.

Guidelines on optimizing the use of proton pump inhibitors: PPI stewardship.

Proton pump inhibitors (PPIs) have been available for over three decades and are among the most commonly prescribed medications. They are effective in treating a variety of gastric acid-related disorders. They are freely available and based on current evidence, use of PPIs for inappropriate indications and duration appears to be common. Over the years, concerns have been raised on the safety of PPIs as they have been associated with several adverse effects. Hence, there is a need for PPI stewardship to promote the use of PPIs for appropriate indication and duration. With this objective, the Indian Society of Gastroenterology has formulated guidelines on the rational use of PPIs. The guidelines were developed using a modified Delphi process. This paper presents these guidelines in detail, including the statements, review of literature, level of evidence and recommendations. This would help the clinicians in optimizing the use of PPIs in their practice and promote PPI stewardship.

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.

Inflammatory bowel disease (IBD)-disk accurately predicts the daily life burden and parallels disease activity in patients with IBD.

BACKGROUND/AIMS: The inflammatory bowel disease (IBD)-disk is a validated, visual, 10-item, self-administered questionnaire used to evaluate IBD-related disability. The present study aimed to evaluate IBD-disk in assessment of IBD daily life burden and its relation with disease activity. METHODS: A cross-sectional study was conducted between June 2021 and December 2021. Patients with IBD were asked to complete the IBD-disk and a visual analogue scale of IBD daily-life burden (scored from 0-10, score >5 indicative of high burden). The internal consistency of IBD-disk, correlation with IBD daily life burden and disease activity (assessed by partial Mayo score and Harvey Bradshaw Index in patients with ulcerative colitis [UC] and Crohn's disease [CD], respectively) and diagnostic performance of IBD-disk to detect high burden were analyzed. RESULTS: Out of the 546 patients (mean age 40.33±13.74 years, 282 [51.6%] males) who completed the IBD-disk, 464 (84.98%) had UC and the remaining (n=82, 15.02%) had CD. A total of 311 patients (291 UC and 20 CD; 56.95%) had active disease. The mean IBD-disk total score and IBD daily life burden were 18.39±15.23 and 2.45±2.02, respectively. The IBD-disk total score correlated strongly with the IBD daily life burden (ρ=0.94, P<0.001), moderately with partial Mayo score (ρ=0.50) and weakly with Harvey Bradshaw Index (ρ=0.34). The IBD-disk total score >30 predicted high IBD daily-life burden. CONCLUSIONS: The IBD-disk accurately predicts the daily life burden and parallels disease activity in patients with IBD and can be applied in clinical practice. (Intest Res, Published online).

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.

Nutritional screening and assessment in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is associated with increased risk of malnutrition and sarcopenia. Both malnutrition and sarcopenia negatively impact the clinical course, quality of life, response to therapy, and surgical outcomes in patients with IBD. This review article highlights the importance of nutritional assessment in patients with IBD and also discusses the different nutritional screening and assessment tools, and measures to detect sarcopenia in relation to IBD. Identification of malnutrition and sarcopenia will allow prioritization of the corrective actions, such as nutritional rehabilitation, to improve clinical outcomes. An approach to the evaluation of nutritional status in patients with IBD is also suggested.

Maintaining infliximab induced clinical remission with azathioprine and 5-aminosalicylates in acute severe steroid-refractory ulcerative colitis has lower cost and high efficacy (MIRACLE): a multicenter study.

BACKGROUND/AIMS: Infliximab (IFX) has been used to induce and maintain remission in patients with severe steroid-refractory ulcerative colitis (UC). Long-term use of biologics in developing countries is limited by high cost and frequent side effects. An optimal maintenance strategy in these patients needs to be established. METHODS: A retrospective analysis of maintenance of clinical remission with combination of azathioprine (AZA) and 5-aminosalicylates (5-ASA) in patients with severe steroidrefractory UC where IFX (5 mg/kg intravenously at weeks 0, 2, 6) had been used only as an induction therapy was done at 2 centers in India. Primary outcome was the proportion of patients maintaining corticosteroid-free sustained clinical remission (SCR) at the end of study period. Rates of relapse and cost of therapy were also analyzed. RESULTS: Of the 137 patients who received rescue IFX induction therapy, 77 (56.2%) achieved clinical remission (mean age 34.81 ± 13.32 years, 68.83% males, median follow-up 4 years, range 3 months to 6 years) and were included. Cumulative corticosteroid-free SCR was maintained in 68%, 59%, 42%, and 35% patients at 1, 2, 4, and 6 years respectively. Sixty-seven relapses were observed in 33 patients. Majority of the relapses (45/67, 67.16%) occurred within first 2 years of follow-up. Two relapses were managed with re-induction with IFX, one required colectomy, whereas all other responded to repeat course(s) of corticosteroids. Annual per capita maintenance therapy with 5-ASA and AZA was cheaper by US$ 4,526 compared to maintaining remission with IFX. CONCLUSIONS: Clinical remission achieved with IFX induction therapy in severe steroid-refractory UC can be sustained over long time with a combination of AZA and 5-ASA.

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.