Efficacy and tolerability of hyperbaric oxygen therapy in small bowel stricturing Crohn’s disease: a pilot study

( Bhaskar Kante ),( Pabitra Sahu ),( Saurabh Kedia ),( Sudheer K. Vuyyuru ),( Kapil Soni ),( Maneesh Singhal ),( Raju Sharma ),( Govind Makharia ),( Vineet Ahuja ) 대한장연구학회 2022 Intestinal Research Vol.20 No.2

Background/Aims: Existing therapeutic options for complicated Crohn’s disease (CD) like biologics and surgery are limited by inadequate long-term efficacy, cost, and adverse effects. Tissue hypoxia is important in CD pathogenesis and may be ameliorated with hyperbaric oxygen therapy (HBOT). We assessed the efficacy and tolerability of HBOT in small bowel stricturing CD. Methods: This pilot study included patients of small bowel stricturing CD (from April 2019 to January 2020) who underwent HBOT. These patients were refractory to conventional medical treatment or had multiple strictures not amenable to resection. Each session of HBOT was given for 60 minutes with a pressure of 1.5-2.5 atm. Clinical, biochemical responses and Short Inflammatory Bowel Disease (SIBD) questionnaire were evaluated at 2 and 6 months, and radiological response was evaluated at 6 months. Results: Fourteen patients (mean age, 42.9±15.7 years; male, 50%) were subjected to 168 HBOT sessions. Thirteen patients (92.7%) had strictures and 1 patient had enterocutaneous fistula in addition. Median number of HBOT sessions was 11 (range, 3-20) which were administered over a median of 4 weeks. Most patients tolerated it well except 1 who had hemotympanum. At 2 and 6 months of follow-up, 64.2% of patients had a clinical response, 50% and 64.2% of patients had clinical remission respectively. Steroid-free clinical remission was seen in 8 (57%) of patients with radiological improvement in 50%. There was a significant improvement in SIBD scores at 2-month follow-up (59.4 vs. 44.5, P=0.03). Conclusions: HBOT can be a safe and effective therapeutic option in patients with stricturing small bowel CD refractory to conventional medical treatment. (Intest Res 2022;20:231-239)

Interaction of XRCC1 and XPD Gene Polymorphisms with Lifestyle and Environmental Factors Regarding Susceptibility to Lung Cancer in a High Incidence Population in North East India

Saikia, Bhaskar Jyoti,Phukan, Rup Kumar,Sharma, Santanu Kumar,Sekhon, Gaganpreet Singh,Mahanta, Jagadish Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.5

Background: This study aimed to explore the role of XRCC1 (Arg399Gln) and XPD (Lys751Gln) gene polymorphisms, lifestyle and environmental factors as well as their possible interactions in propensity to develop lung cancer in a population with high incidence from North East India. Materials and Methods: A total of 272 lung cancer cases and 544 controls were collected and XRCC1 (Arg399Gln) and XPD (Lys751Gln) genotypes were analyzed using a polymerase chain reaction based restriction fragment length polymorphism assay. Conditional multiple logistic regression analysis was used to calculate adjusted odds ratios and 95% confidence intervals after adjusting for confounding factors. Results: The combined Gln/Gln genotype of XRCC1 and XPD genes (OR=2.78, CI=1.05-7.38; p=0.040) was significantly associated with increased risk for lung cancer. Interaction of XRCC1Gln/Gln genotype with exposure of wood combustion (OR=2.56, CI=1.16-5.66; p=0.020), exposure of cooking oil fumes (OR=3.45, CI=1.39-8.58; p=0.008) and tobacco smoking (OR=2.54, CI=1.21-5.32; p=0.014) and interaction of XPD with betel quid chewing (OR=2.31, CI=1.23-4.32; p=0.009) and tobacco smoking (OR=2.13, CI=1.12-4.05; p=0.022) were found to be significantly associated with increased risk for lung cancer. Conclusions: Gln/Gln alleles of both XRCC1 and XPD genes appear to amplify the effects of household exposure, smoking and betel quid chewing on lung cancer risk in the study population.

Efficacy and tolerability of exclusive enteral nutrition in adult patients with complicated Crohn’s disease

( Sanchit Sharma ),( Arti Gupta ),( Saurabh Kedia ),( Samagra Agarwal ),( Namrata Singh ),( Sandeep Goyal ),( Saransh Jain ),( Vipin Gupta ),( Pabitra Sahu ),( Sudheer Kumar Vuyyuru ),( Bhaskar Kante 대한장연구학회 2021 Intestinal Research Vol.19 No.3

Background/Aims: Exclusive enteral nutrition (EEN), an established modality for pediatric Crohn’s disease (CD) is seldomly utilized in adults. The present study reports the outcome of EEN in adult CD patients at a tertiary care hospital in India. Methods: This was a retrospective analysis of CD patients who received EEN as a sole modality/adjunct to other treatment. The primary and secondary outcomes changed in Crohn’s Disease Activity Index (CDAI), and clinical response (decline in CDAI >70), respectively, at 4 and 8 weeks. Subgroup analysis evaluated response across different phenotypes, EEN formulations and prior treatment. Linear mixed effect model was created to assess the predictors of EEN response. Results: Thirty-one CD patients received EEN over median duration of 4 weeks (range, 2-6 weeks). CDAI showed a significant improvement post EEN at 4 (baseline 290 [260-320] vs. 240 [180-280], P=0.001) and 8 weeks (baseline 290 [260-320] vs. 186 [160-240], P=0.001), respectively. The cumulative clinical response rates at 4 and 8 weeks were 37.3% and 80.4% respectively. The clinical response rates at 8 weeks across B1 (n=4), B2 (n=18), and B3 (n=9) phenotypes were 50%, 78.8%, and 100% respectively (log-rank test, P=0.093). The response rates at 8 weeks with polymeric (n=8) and semi-elemental diet (n=23) were 75% and 82.6% respectively (log-rank test, P=0.49). Baseline CDAI (odds ratio, 1.008; 95% confidence interval, 1.002-1.017; P=0.046) predicted response to EEN. Conclusions: EEN was effective in inducing clinical response across different phenotypes of CD. Baseline disease activity remained the most important predictor of clinical response to EEN. (Intest Res 2021;19:291-300)

Association of a p53 Codon 72 Gene Polymorphism with Environmental Factors and Risk of Lung Cancer: a Case Control Study in Mizoram and Manipur, a High Incidence Region in North East India

Saikia, Bhaskar Jyoti,Das, Mandakini,Sharma, Santanu Kumar,Sekhon, Gaganpreet Singh,Zomawia, Eric,Singh, Yanglem Mohen,Mahanta, Jagadish,Phukan, Rup Kumar Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.24

Background: A very high incidence of lung cancer is observed in Mizoram and Manipur, North East India. We conducted a population based case control study to establish associations of p53 codon 72 polymorphisms and interactions with environmental factors for this high incidence. Material and Methods: A total of 272 lung cancer cases and 544 controls matched for age (${\pm}5years$), sex and ethnicity were collected and p53 codon 72 polymorphism genotypes were analyzed using a polymerase chain based restriction fragment length polymorphism assay. We used conditional multiple logistic regression analysis to calculate adjusted odds ratios and 95% confidence intervals after adjusting for confounding factors. Results: p53 Pro/Pro genotype was significantly associated with increased risk of lung cancer in the study population (adjusted OR=2.14, CI=1.35-3.38, p=0.001). Interactions of the p53 Pro/Pro genotype with exposure to wood smoke (adjusted OR=3.60, CI=1.85-6.98, p<0.001) and cooking oil fumes (adjusted OR=3.27, CI=1.55-6.87, p=0.002), betel quid chewing (adjusted OR=3.85, CI=1.96-7.55, p<0.001), tobacco smoking (adjusted OR=4.42, CI=2.27-8.63, p<0.001) and alcohol consumption (adjusted OR=3.31, CI=1.10-10.03, p=0.034) were significant regarding the increased risk of lung cancer in the study population. Conclusions: The present study provided preliminary evidence that a p53 codon 72 polymorphism may effect lung cancer risk in the study population, interacting synergistically with environmental factors.

Promoter Methylation of MGMT Gene in Serum of Patients with Esophageal Squamous Cell Carcinoma in North East India

Das, Mandakini,Sharma, Santanu Kumar,Sekhon, Gaganpreet Singh,Saikia, Bhaskar Jyoti,Mahanta, Jagadish,Phukan, Rup Kumar Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.22

Background: Promoter hypermethylation is a common event in human cancer. O6-methylguanine-DNA methyltransferase (MGMT) is a gene involved in DNA repair, which is methylated in a variety of cancers. We aimed to explore the methylation status of MGMT gene among the North Eastern population where esophageal cancer incidence and exposure to carcinogens like nitrosamines is high. Materials and Methods: A total of 100 newly diagnosed esophageal cancer cases along with equal number of age, sex and ethnicity matched controls were included in this study. Methylation specific PCR was used to determine the MGMT methylation status in serum samples. Results: Aberrant promoter methylation of the MGMT gene was detected in 70% of esophageal cancer cases. Hypermethylation of MGMT gene was found to be influenced by environmental factors like betel quid and tobacco which contain potent carcinogens like nitrosamines. Tobacco chewing and tobacco smoking habit synergistically with MGMT methylation elevated the risk for esophageal cancer development [adjusted OR=5.02, 95% CI=1.35-18.74; p=0.010 for tobacco chewing and Adjusted OR=3.00, 95% CI=1.22-7.36; p=0.014 for tobacco smoking]. Conclusions: Results suggest that the DNA hypermethylation of MGMT is an important mechanism for MGMT gene silencing resulting in esophageal cancer development and is influenced by the environmental factors. Thus MGMT hypermethylation can be used as a biomarker for esophageal cancer in high incidence region of North East India.

Dosimetric comparison of IMRT versus 3DCRT for post-mastectomy chest wall irradiation

Rastogi, Kartick,Sharma, Shantanu,Gupta, Shivani,Agarwal, Nikesh,Bhaskar, Sandeep,Jain, Sandeep The Korean Society for Radiation Oncology 2018 Radiation Oncology Journal Vol.36 No.1

Purpose: To compare the dose distribution of three-dimensional conformal radiation therapy (3DCRT) with intensity-modulated radiation therapy (IMRT) for post-mastectomy radiotherapy (PMRT) to left chest wall. Materials and Methods: One hundred and seven patients were randomised for PMRT in 3DCRT group (n = 64) and IMRT group (n = 43). All patients received 50 Gy in 25 fractions. Planning target volume (PTV) parameters-$D_{near-max}$ ($D_2$), $D_{near-min}$ ($D_{98}$), $D_{mean}$, $V_{95}$, and $V_{107}$-homogeneity index (HI), and conformity index (CI) were compared. The mean doses of lung and heart, percentage volume of ipsilateral lung receiving 5 Gy ($V_5$), 20 Gy ($V_{20}$), and 55 Gy ($V_{55}$) and that of heart receiving 5 Gy ($V_5$), 25 Gy ($V_{25}$), and 45 Gy ($V_{45}$) were extracted from dose-volume histograms and compared. Results: PTV parameters were comparable between the two groups. CI was significantly improved with IMRT (1.127 vs. 1.254, p < 0.001) but HI was similar (0.094 vs. 0.096, p = 0.83) compared to 3DCRT. IMRT in comparison to 3DCRT significantly reduced the high-dose volumes of lung ($V_{20}$, 22.09% vs. 30.16%; $V_{55}$, 5.16% vs. 10.27%; p < 0.001) and heart ($V_{25}$, 4.59% vs. 9.19%; $V_{45}$, 1.85% vs. 7.09%; p < 0.001); mean dose of lung and heart (11.39 vs. 14.22 Gy and 4.57 vs. 8.96 Gy, respectively; p < 0.001) but not the low-dose volume ($V_5$ lung, 61.48% vs. 51.05%; $V_5$ heart, 31.02% vs. 23.27%; p < 0.001). Conclusions: For left sided breast cancer, IMRT significantly improves the conformity of plan and reduce the mean dose and high-dose volumes of ipsilateral lung and heart compared to 3DCRT, but 3DCRT is superior in terms of low-dose volume.

Dosimetric comparison of IMRT versus 3DCRT for post-mastectomy chest wall irradiation

Kartick Rastogi,Shantanu Sharma,Shivani Gupta,Nikesh Agarwal,MBBS,Sandeep Bhaskar,Sandeep Jain 대한방사선종양학회 2018 Radiation Oncology Journal Vol.36 No.1

Purpose: To compare the dose distribution of three-dimensional conformal radiation therapy (3DCRT) with intensity-modulated radiation therapy (IMRT) for post-mastectomy radiotherapy (PMRT) to left chest wall. Materials and Methods: One hundred and seven patients were randomised for PMRT in 3DCRT group (n = 64) and IMRT group (n = 43). All patients received 50 Gy in 25 fractions. Planning target volume (PTV) parameters-D near-max (D 2 ), D near-min (D 98 ), D mean , V 95 , and V 107 -homogeneity index (HI), and conformity index (CI) were compared. The mean doses of lung and heart, percentage volume of ipsilateral lung receiving 5 Gy (V 5 ), 20 Gy (V 20 ), and 55 Gy (V 55 ) and that of heart receiving 5 Gy (V 5 ), 25 Gy (V 25 ), and 45 Gy (V 45 ) were extracted from dose-volume histograms and compared. Results: PTV parameters were comparable between the two groups. CI was significantly improved with IMRT (1.127 vs. 1.254, p < 0.001) but HI was similar (0.094 vs. 0.096, p = 0.83) compared to 3DCRT. IMRT in comparison to 3DCRT significantly reduced the high-dose volumes of lung (V 20 , 22.09% vs. 30.16%; V 55 , 5.16% vs. 10.27%; p < 0.001) and heart (V 25 , 4.59% vs. 9.19%; V 45 , 1.85% vs. 7.09%; p < 0.001); mean dose of lung and heart (11.39 vs. 14.22 Gy and 4.57 vs. 8.96 Gy, respectively; p < 0.001) but not the low-dose volume (V 5 lung, 61.48% vs. 51.05%; V 5 heart, 31.02% vs. 23.27%; p < 0.001). Conclusions: For left sided breast cancer, IMRT significantly improves the conformity of plan and reduce the mean dose and high-dose volumes of ipsilateral lung and heart compared to 3DCRT, but 3DCRT is superior in terms of low-dose volume.

Addition of computed tomography chest increases the diagnosis rate in patients with suspected intestinal tuberculosis

( Saurabh Kedia ),( Raju Sharma ),( Sudheer Kumar Vuyyuru ),( Deepak Madhu ),( Pabitra Sahu ),( Bhaskar Kante ),( Prasenjit Das ),( Ankur Goyal ),( Karan Madan ),( Govind Makharia ),( Vineet Ahuja ) 대한장연구학회 2022 Intestinal Research Vol.20 No.2

Background/Aims: Intestinal tuberculosis (ITB) is difficult to diagnose due to poor sensitivity of definitive diagnostic tests. ITB may be associated with concomitant pulmonary tuberculosis (PTB) which may remain undetected on chest X-ray. We assessed the role of contrast enhanced computed tomography (CECT) chest in detecting the prevalence of active PTB, and increasing the diagnostic yield in patients with suspected ITB. Methods: Consecutive treatment naïve patients with suspected ITB (n=200) who underwent CECT chest (n=88) and had follow-up duration>1 year were recruited in this retrospective study (February 2016 to October 2018). ITB was diagnosed in the presence of caseating granuloma, positive acid fast stain or culture for Mycobacterium tuberculosis on biopsy, presence of necrotic lymph nodes (LNs) on CT enterography or positive response to anti-tubercular therapy. Evidence of active tuberculosis on CECT-chest was defined as presence of centrilobular nodules with or without consolidation/miliary nodules/thick-walled cavity/enlarged necrotic mediastinal LNs. Results: Sixty-five of eighty-eight patients (mean age, 33.8±12.8 years; 47.7% of females) were finally diagnosed as ITB (4-caseating granuloma on biopsy, 12-necrotic LNs on CT enterography, 1-both, and 48-response to anti-tubercular therapy) and 23 were diagnosed as Crohn’s disease. Findings of active TB on CECT chest with or without necrotic abdominal LNs were demonstrated in 5 and 20 patients, respectively. No patient with Crohn’s disease had necrotic abdominal LNs or active PTB. Addition of CECT chest in the diagnostic algorithm improved the sensitivity of ITB diagnosis from 26.2% to 56.9%. Conclusions: Addition of CECT chest significantly improves the sensitivity for definite diagnosis in a patient with suspected ITB. (Intest Res 2022;20:184-191)

Plasmodium falciparum apicoplast and its transcriptional regulation through calcium signaling

Praveen Rai,Drista Sharma,Rani Soni,Nazia Khatoon,Bhaskar Sharma,Tarun Kumar Bhatt 한국미생물학회 2017 The journal of microbiology Vol.55 No.4

Malaria has been present since ancient time and remains amajor global health problem in developing countries. Plasmodiumfalciparum belongs to the phylum Apicomplexan,largely contain disease-causing parasites and characterizedby the presence of apicoplast. It is a very essential organelleof P. falciparum responsible for the synthesis of key moleculesrequired for the growth of the parasite. Indispensablenature of apicoplast makes it a potential drug target. Calciumsignaling is important in the establishment of malaria parasiteinside the host. It has been involved in invasion and egressof merozoites during the asexual life cycle of the parasite. Calcium signaling also regulates apicoplast metabolism. Therefore,in this review, we will focus on the role of apicoplast inmalaria biology and its metabolic regulation through Ca++signaling.

Pharmacokinetics and hypoglycemic effect of gliclazide loaded in Isabgol husk mucilage microparticles

Kumar Vipin,Mazumder Bhaskar,Sharma Prince Prashant,Ahmed Yusra 한국약제학회 2021 Journal of Pharmaceutical Investigation Vol.51 No.2

Purpose Among the several therapeutic agents available for the management of diabetes mellitus, sulfonylureas such as gliclazide have several advantages. The hypoglycemic effect and bioavailability of gliclazide loaded in Isabgol husk mucilage microparticles were assessed. The hypoglycemic effect of drug-loaded microparticles was compared with that of pure gliclazide. Methods Gliclazide was incorporated into Isabgol husk mucilage microparticles using an emulsification-crosslinking technique. Gliclazide characterization was performed using a chromatographic method. Results Gliclazide loading in the microparticles was up to 91.23 ± 0.981% w/w. The pharmacokinetic parameters for pure gliclazide (control) were different from those of gliclazide loaded in microparticles (test). After oral administration, the AUC 0–24 h of gliclazide in blood samples of the control and test groups was 10.840 ± 0.018 and 17.608 ± 0.035 μg/(mL h), respectively. In 24 h after oral administration, the percentage reduction from the baseline glucose level in diabetic rabbits was 36.66 ± 4.509% and 98.11 ± 1.018% for the test and control groups, respectively. Conclusion The prolonged hypoglycemic effect and increased bioavailability of gliclazide loaded in Isabgol husk microparticles compared with those of pure drug indicate the applicability of the microparticulate formulation as a novel anti-diabetic drug delivery system.