A simple phenotypic classification for celiac disease

( Ajit Sood ),( Vandana Midha ),( Govind Makharia ),( B. K. Thelma ),( Shivalingappa S Halli ),( Varun Mehta ),( Ramit Mahajan ),( Vikram Narang ),( Kriti Sood ),( Kirandeep Kaur ) 대한장연구학회 2018 Intestinal Research Vol.16 No.2

Background/Aims: Celiac disease is a global health problem. The presentation of celiac disease has unfolded over years and it is now known that it can manifest at different ages, has varied presentations, and is prone to develop complications, if not managed properly. Although the Oslo definitions provide consensus on the various terminologies used in literature, there is no phenotypic classification providing a composite diagnosis for the disease. Methods: Various variables identified for phenotypic classification included age at diagnosis, age at onset of symptoms, clinical presentation, family history and complications. These were applied to the existing registry of 1,664 patients at Dayanand Medical College and Hospital, Ludhiana, India. In addition, age was evaluated as below 15 and below 18 years. Cross tabulations were used for the verification of the classification using the existing data. Expert opinion was sought from both international and national experts of varying fields. Results: After empirical verification, age at diagnosis was considered appropriate in between A1 (<18) and A2 (≥18). The disease presentation has been classified into 3 types-P1 (classical), P2 (non-classical) and P3 (asymptomatic). Complications were considered as absent (C0) or present (C1). A single phenotypic classification based on these 3 characteristics, namely age at the diagnosis, clinical presentation, and intestinal complications (APC classification) was derived. Conclusions: APC classification (age at diagnosis, presentation, complications) is a simple disease explanatory classification for patients with celiac disease aimed at providing a composite diagnosis. (Intest Res 2018;16:288-292)

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

( Ajit Sood ),( Kirandeep Kaur ),( Arshdeep Singh ),( Vandana Midha ),( Ramit Mahajan ),( Namita Bansal ),( Varun Mehta ),( Dharmatma Singh ) 대한장연구학회 2021 Intestinal Research Vol.19 No.3

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. (Intest Res 2021;19:282-290)

Efficacy of fecal microbiota therapy in steroid dependent ulcerative colitis: a real world intention-to-treat analysis

( Ajit Sood ),( Ramit Mahajan ),( Garima Juyal ),( Vandana Midha ),( Charanpreet Singh Grewal ),( Varun Mehta ),( Arshdeep Singh ),( Mohan C Joshi ),( Vikram Narang ),( Kirandeep Kaur ),( Hasrat Sidhu 대한장연구학회 2019 Intestinal Research Vol.17 No.1

Background/Aims: Four high-quality randomized controlled trials have proven the efficacy of fecal microbiota transplantation (FMT) in active ulcerative colitis (UC). We assessed the efficacy of FMT in a real-world setting involving steroid-dependent patients with UC. Methods: This was a single-center prospective analysis of data from steroid-dependent patients with UC treated with FMT from September 2015 to September 2017 at the Dayanand Medical College, a tertiary care center in India. Fecal samples from random unrelated donors were administered through colonoscopy at weeks 0, 2, 6, 10, 14, 18, and 22. The primary outcome was achievement of steroid-free clinical remission, and the secondary outcomes were clinical response and endoscopic remission at 24 weeks. Modified intention-to-treat analysis was performed, which included subjects who underwent at least 1 FMT. Results: Of 345 patients with UC treated during the study period, 49 (14.2%) had steroid-dependent UC. Of these 49 patients, 41 underwent FMT: 33 completed 7 sessions over 22 weeks according to the protocol, and 8 discontinued treatment (non-response, 5; lost to follow-up, 2; and fear of adverse effects, 1). At week 24, steroid-free clinical remission was achieved in 19 out of 41 (46.3%) patients, whereas clinical response and endoscopic remission were achieved in 31 out of 41 (75.6%) and 26 out of 41 (63.4%) patients, respectively. All patients with clinical response were able to withdraw steroids. There were no serious adverse events necessitating discontinuation. Conclusions: A multisession FMT via the colonoscopic route is a promising therapeutic option for patients with steroid-dependent UC, as it can induce clinical remission and aid in steroid withdrawal. (Intest Res 2019;17:78-86)

Colitis and Crohn’s Foundation (India) consensus statements on use of 5-aminosalicylic acid in inflammatory bowel disease

( Ajit Sood ),( Vineet Ahuja ),( Vandana Midha ),( Saroj Kant Sinha ),( C. Ganesh Pai ),( Saurabh Kedia ),( Varun Mehta ),( Sawan Bopanna ),( Philip Abraham ),( Rupa Banerjee ),( Shobna Bhatia ),( Kar 대한장연구학회 2020 Intestinal Research Vol.18 No.4

Despite several recent advances in therapy in inflammatory bowel disease (IBD), 5-aminosalicylic acid (5-ASA) therapy has retained its place especially in ulcerative colitis. This consensus on 5-ASA is obtained through a modified Delphi process, and includes guiding statements and recommendations based on literature evidence (randomized trials, and observational studies), clinical practice, and expert opinion on use of 5-ASA in IBD by Indian gastroenterologists. The aim is to aid practitioners in selecting appropriate treatment strategies and facilitate optimal use of 5-ASA in patients with IBD. (Intest Res 2020;18:355-378)

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

( Ajit Sood ),( Arshdeep Singh ),( Ritu Sudhakar ),( Vandana Midha ),( Ramit Mahajan ),( Varun Mehta ),( Yogesh Kumar Gupta ),( Kirandeep Kaur ) 대한장연구학회 2020 Intestinal Research Vol.18 No.2

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. (Intest Res 2020;18:184-191)

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

( Ajit Sood ),( Kirandeep Kaur ),( Ramit Mahajan ),( Vandana Midha ),( Arshdeep Singh ),( Sarit Sharma ),( Amarender Singh Puri ),( Bhabhadev Goswami ),( Devendra Desai ),( C. Ganesh Pai ),( Kiran Ped 대한장연구학회 2021 Intestinal Research Vol.19 No.2

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. (Intest Res 2021;19:206-216)

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

Ajit Sood,Ramit Mahajan,Arshdeep Singh,Vandana Midha,Varun Mehta 대한장연구학회 2022 Intestinal Research Vol.20 No.3

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.

A Tuber Lectin from Arisaema jacquemontii Blume with Anti-insect and Anti-proliferative Properties

( Manpreet Kaur ),( Kuljinder Singh ),( Pushpinder Jai Rup ),( Sukhdev Singh Kamboj ),( Ajit Kumar Saxena ),( Madhunika Sharma ),( Madhulika Bhagat ),( Sarvesh Kumar Sood ),( Jatinder Singh ) 생화학분자생물학회 2006 BMB Reports Vol.39 No.4

A Tuber Lectin from Arisaema jacquemontii Blume with Anti-insect and Anti-proliferative Properties

Kaur, Manpreet,Singh, Kuljinder,Rup, Pushpinder Jai,Kamboj, Sukhdev Singh,Saxena, Ajit Kumar,Sharma, Madhunika,Bhagat, Madhulika,Sood, Sarvesh Kumar,Singh, Jatinder Korean Society for Biochemistry and Molecular Biol 2006 Journal of biochemistry and molecular biology Vol.39 No.4

A tuber lectin from Arisaema jacquemontii Blume belonging to family Araceae was purified by employing a single step affinity chromatography using column of asialofetuin-linked amino activated silica beads and the bound lectin was eluted with 100 mM glycine-HCl buffer pH 2.5. The purified A. jacquemontii lectin (AJL) showed a single protein band with an apparent molecular mass of 13.4 kDa when submitted to SDS-polyacrylamide gel electrophoresis under reducing as well as non-reducing conditions. The native molecular mass of AJL determined by gel filtration on a Biogel P-200 column was 52 kDa and its carbohydrate content was estimated to be 3.40%. Thus AJL is a tetrameric glycoprotein. The purified lectin agglutinated erythrocytes from rabbit but not from human. Its activity was not inhibited by any of the mono- and disaccharides tested except N-acetyl-D-lactosamine having minimal inhibitory sugar concentration (MIC) 25 mM. Among the glycoproteins tested only asialofetuin was found to be inhibitory (MIC $125\;{\mu}g/mL$). A single band was obtained in native PAGE at pH 4.5 while PAGE at pH 8.3 showed two bands. Isoelectric focusing of AJL gave multiple bands in the pI range of 4.6-5.5. When incorporated in artificial diet AJL significantly affected the development of Bactrocera cucurbitae (Coquillett) larvae indicating the possibility of using this lectin in a biotechnological strategy for insect management of cucurbits. Larvae fed on artificial diet containing sub-lethal dose of AJL showed a significant decrease in acid phosphatase and alkaline phosphatase activity while esterase activity markedly increased as compared to larvae fed on diet without lectin. Out of various human cancer cell lines employed in sulphorhodamine B (SRB) assay, this lectin was found to have appreciable inhibitory effect on the in vitro proliferation of HCT-15, HOP-62, SW-620, HT-29, IMR-32, SKOV-3, Colo-205, PC-3, HEP-2 and A-549 cancer cell lines by 82, 77, 73, 70, 41, 41, 37, 29, 21 and 21% respectively.

Efficacy and safety of the adalimumab biosimilar Exemptia as induction therapy in moderate-to-severe ulcerative colitis

Vandana Midha,Ramit Mahajan,Varun Mehta,Vikram Narang,Arshdeep Singh,Kirandeep Kaur,Ajit Sood 대한장연구학회 2018 Intestinal Research Vol.16 No.1

Background/Aims: Data on the efficacy and safety of the adalimumab biosimilar Exemptia are limited. Methods: Patients with moderate-to-severe active steroid-refractory ulcerative colitis (UC) treated at Dayanand Medical College and Hospital,India were offered cyclosporine A, biologicals or biosimilars, or surgery. A retrospective analysis was conducted on patients who were treated with the adalimumab biosimilar, Exemptia. These patients were administered an induction dosing scheduleof 160 mg Exemptia at week 0, 80 mg at week 2, and then 40 mg every other week from week 4 to 8. The clinical response andremission were assessed at week 8 using Mayo score. Results: A total of 29 patients (62.1% male; mean age, 34.9 ± 9.7 years)with moderate-to-severe steroid-refractory active UC (mean disease duration, 6.3±5.1 years; pancolitis in 9 patients [31.1%];left-sided colitis in 20 patients [68.9%]) were treated with the Exemptia induction dosing schedule. The mean Mayo score at presentation was 8.2±1.4. At week 8, clinical response was observed in 7 patients (24.1%), whereas clinical remission was observed only in 1 patient (3.5%). Among the non-responders (n=21), 4 patients required colectomy, 1 died, 1 was lost to follow-up, 10 were offered fecal microbiota transplant, 3 were administered infliximab, and 2 patients were administered cyclosporineand tacrolimus, respectively. Four patients (13.8%) developed extrapulmonary tuberculosis. Conclusions: The adalimumab biosimilar Exemptia has limited efficacy for the attainment of clinical response and remission in moderate-to-severe steroid-refractory UC, with a significant risk of acquisition or reactivation of tuberculosis in developing countries such as India.