Methylation study of tumor suppressor genes in human aberrant crypt foci, colorectal carcinomas, and normal colon.

BACKGROUND: Aberrant crypt foci (ACF) are the earliest preneoplastic lesions in human colon, identifiable on chromoendoscopic screening. Our objective was to evaluate the %methylation of APC, CDKN2A, MLH1, RASSF1, MGMT, and WIF1 tumor suppressor genes (TSG) in ACF, corresponding colorectal carcinomas (CRC), and normal colonic mucosal controls. METHODS: In this study, macroscopically normal-appearing mucosal flaps were sampled 5-10 cm away from the tumor mass from 302 fresh colectomy specimens to identify ACF-like lesions. Thirty-five cases with multiple ACFs were selected (n 35) as the main study group, with corresponding sections from CRC (n 35) as disease controls, and mucosal tissue blocks from 20 colectomy specimens (normal controls), operated for non-neoplastic pathologies. Genomic DNA was extracted, and methylation-specific polymerase chain reaction (PCR) was performed on a customized methylation array model. %Methylation data were compared among the groups and with clinicopathological parameters. Selected target mRNA and protein expression studies were performed. RESULTS: %Methylation of TSGs in ACF was intermediate between normal colon and CRC, although a statistically significant difference was observed only for the WIF1 gene (P < 0.01). Also, there was increased nuclear ß-catenin expression and upregulation of CD44-positive cancer-stem cells in ACF and CRCs than in controls. Right-sided ACFs and dysplastic ACFs had a higher %methylation of CDKN2A (P < 0.01), whereas hyperplastic ACFs had a higher %methylation of RASSF1 (P 0.04). The topographic characteristics of ACFs did not correlate with TSG %methylation. CONCLUSIONS: Early epigenetic methylation of WIF1 gene is one of the mechanisms for ACF development in human colon.

Acinar cystic transformation of the pancreatic body and tail in an elderly male patient: A case report.

Acinar cystic transformation (ACT) is a rare benign cystic lesion of the pancreas reported in elderly women. ACT can be easily confused with other cystic lesions of the pancreas, such as intraductal papillary neoplasm and serous and mucinous neoplasms, on imaging, especially when detected radiologically in a male patient as the index case. A preoperative histological examination can establish a diagnosis and avoid extensive surgical resection. We hereby report a case of ACT in a 69-year-old male patient that affected the body and tail region of the pancreas.

Postoperative pulmonary complications with high versus standard FiO2 in adult patients undergoing major abdominal surgery: A noninferiority trial.

BACKGROUND: Despite the possible clinical benefit of high intraoperative oxygen therapy on surgical site infection, the effect on postoperative respiratory function is debatable. However, it remains yet to be elucidated whether hyperoxia due to a high fraction of inspired oxygen used in conjunction with lung protective ventilation can lead to increased incidence of postoperative pulmonary complications. METHODS: In this noninferiority randomized trial, an intraoperative high fraction of inspired oxygen of 0.8 (group H) was compared to a standard fraction of inspired oxygen of 0.3 to 0.4 (group S) in adult patients undergoing major elective or emergency surgery. A lung protective ventilation strategy was employed in all patients, including volume control ventilation with a tidal volume of 6 to 8 mL/kg of predicted body weight, respiratory rate of 12 beats per minute, and positive end-expiratory pressure of 5 to 8 cm H2O. Postoperative pulmonary complications were assessed on postoperative days 3 and 5 by the Melbourne group scale. RESULTS: In this trial, n = 226 patients were randomized; among them, 130 patients underwent routine surgery, and 96 patients underwent emergency surgery. The median (interquartile range) of the patients was 48 (35-58) years, and 47.3% were female. Melbourne group scale scores at postoperative day 3 (median [interquartile range] 2 [1-4] in group S vs 2 [1-3] in group H; the difference in median [95% confidence interval] 0 [0, -1]; P = .13) and day 5 (median [interquartile range] 1 (0-3) in group S vs 1 [0-3] in group H; the difference in median [95% confidence interval] 0 [0, 0.5]; P = .34) were statistically similar in both the groups and the upper margin was within the predefined margin of 1. Incidence of surgical site infection (P = .46), postoperative hospital stay (P = .29), and days alive without antibiotic therapy at postoperative day 28 (P = .95) were similar in both groups. CONCLUSION: High intraoperative fiO2 was noninferior to standard fiO2 in postoperative pulmonary complications in adult patients undergoing major surgery.

Wound Infection After Ileostomy Closure: An Interim Analysis of a Prospective Randomized Study Comparing Primary Versus Circumferential Subcuticular Closure Techniques.

Background: Circumferential subcuticular wound approximation (CSWA) of round shaped skin wounds after ileostomy take down is believed to lower the rates of surgical site infection (SSI). We performed this randomized trial to compare the rates of SSI and other short-term outcomes among primary linear skin closure (PC) and CSWA groups of patients. Patients and Methods: All patients undergoing ileostomy reversal during the study period were randomly assigned to either PC or CSWA. The primary outcome was the incidence of SSI as assessed by ASEPSIS scoring system. The secondary outcomes included healing time, length of post-operative hospital stay, and patients' satisfaction regarding cosmetic outcome, expectations, pain, time of healing, wound care, and activity on a five-point Likert scale. Results: Thirty-one patients (PC = 15; CSWA = 16) underwent ileostomy reversal during the study period. There was no SSI in the PC group whereas three patients developed SSI in the CSWA group but the result was not statistically significant (p = 0.23). The scores for time of healing (p < 0.001), wound care (p = 0.007), and activity (p < 0.001) were significantly better for PC compared with CSWA whereas there was no significant difference in the scores for cosmetic outcome, expectations, and pain. Healing time was shorter in the PC group (6.7 vs. 34.2 days; p < 0.001) whereas the post-operative length of stay was comparable (6.3 vs. 7 days; p = 0.27). Conclusions: Although there was no difference in the incidence of SSI among the two groups, the PC group fared better in terms of mean time to healing and requirement of wound care.

Low prevalence of Clostridioides difficile infection in acute severe ulcerative colitis: A retrospective cohort study from northern India.

BACKGROUND: The incidence of Clostridioides difficile infection (CDI) is high in ulcerative colitis and is associated with disease flares and adverse outcomes. However, the data on the dynamics of CDI in patients with acute severe ulcerative colitis (ASUC) is rather scarce. We evaluated the prevalence of CDI in patients with ASUC. METHODS: This retrospective analysis of a prospectively maintained cohort admitted to the All India Institute of Medical Sciences, India, from May 2016 to December 2021, included patients with ASUC (as per Truelove and Witts criteria) who were tested for CDI. CDI testing was performed using enzyme-linked immunoassay for toxins A and B. Risk factors for developing CDI were analyzed along with short-term outcomes of ASUC. Steroid failure was defined as the need for medical rescue therapy or colectomy. RESULTS: Total 153 patients with ASUC were included (mean age 34.92 ± 12.24 years; males 56.2%; disease duration 36 (IQR: 16-55.5) months, pancolitis 67.3%). Ninety-eight (63.4%), 72 (47%) and 10 (6.5%) patients, respectively, had received steroids, azathioprine and biologics in the past. Forty patients (26.14%) had a prior history of ASUC. Among risk factors for CDI, 14% of the patients had prior admission within 30 days, 22.2% had a recent history of antibiotics and 3.9% had long-term non-steroidal anti-inflammatory drug intake. Only one sample was positive for Clostridioides difficile toxin assay. Tissue Cytomegalovirus DNA-PCR positivity was noted in 57 patients (37.3%). Fifty-seven patients (37.3%) had steroid failure, 35 required medical rescue therapy and 30 (19.6%) required colectomy (eight after medical rescue therapy failure). CONCLUSION: Despite antecedent risk factors for CDI, the overall prevalence of CDI in ASUC was low and the outcomes were determined by underlying disease severity.

Management and outcomes of pseudoaneurysms presenting with late hemorrhage following pancreatic surgery: A six-year experience from a tertiary care center.

BACKGROUND/PURPOSE: Late hemorrhage following pancreatic surgery is associated with significant morbidity and mortality. Pseudoaneurysm (PSA) is an important source of late hemorrhage, which is effectively and safely managed by embolization. We aim to retrospectively review the outcomes of embolization for pseudoaneurysms causing late post-pancreatectomy hemorrhage over a period of six-years at our tertiary care center. METHODS: Between 2014 and 2020, 616 pancreatic surgeries were performed and 25 patients had late hemorrhage (occurring > 24 hours post-operatively). The clinical parameters related to late hemorrhage, associated complications, embolization details, treatment success and their short-and long-term outcomes were analyzed. RESULTS: Sixteen of 25 patients had PSA on digital subtraction angiography. Embolization was performed in these patients with technical and clinical success rates of 94.1% and 100%, respectively. Compared to patients without PSA, patients with PSA had significant hemoglobin drop (2.5 g/dL vs. 1.5 g/dL, p = 0.01), higher incidence of sentinel bleed (50% vs. 11.1%, p = 0.05) and lower requirement for surgery for bleeding (0% vs. 44.4%, p = 0.02). Clincally relevant postoperative pancreatic fistula and bile leak were seen in 72% and 52% of patients, respectively. Eight of these embolized patients died due to sepsis. The long-term outcome was good, once the patients were discharged. CONCLUSION: Late hemorrhage after pancreatic surgery was associated with high mortality due to complications such as pancreatic fistula and bile leak. Sentinel bleeding was an important clinical indicator of PSA. Angiographic embolization is safe and effective without any adverse short or long-term outcomes.

Compensated Advanced Chronic Liver Disease in Nonalcoholic Fatty Liver Disease: Two-Step Strategy is Better than Baveno Criteria.

BACKGROUND: Advanced fibrosis and cirrhosis (compensated advanced chronic liver disease [cACLD]) are clinically indistinguishable and increase risk of developing clinically significant portal hypertension. Baveno VII recommends using elastography to rule out and diagnose cACLD with liver stiffness measurement (LSM) cut-offs of 10/15 kPa. METHODS: In a retrospective analysis of 330 nonalcoholic fatty liver disease (NAFLD) patients, performance of the Baveno VII cut-offs for diagnosing cACLD was compared with newly suggested lower cut-offs (8/12 kPa). A model for detecting cACLD among those with LSM between 8 and 12 kPa was developed and compared with recently published models. RESULTS: Seventy (21.2%) of the 330 NAFLD patients had biopsy-proven cACLD. The Baveno VII cut-offs (10/15 kPa) had a lower sensitivity of 72.8% (60.9-82.8%) and a specificity of 93.4% (89.7-96.1%). Sensitivity and specificity of lower cut-offs (8/12 kPa) were 91.4% (82.3-96.8%) and 88.5% (83.9-92.1%), respectively. Modeling based on the presence of diabetes (odds ratio [OR] 3.625[1.161-11.320], p = 0.027) and serum aspartate aminotransferase (AST) levels (OR 1.636[1.098-2.436], p = 0.015) correctly identified 75.7% of patients with LSM between 8 and 12 kPa. Our model performed best with an area under receiver operator curve (AUROC) of 0.725 (95%CI 0.609-0.822), compared to Papatheodoridi (AUROC 0.626, CI 0.506-.736) and Zhou (AUROC 0.523, CI 0.403-0.640) models. A two-step strategy comprising application of lower LSM cut-offs followed by the predictive model correctly identified the presence of cACLD in 83% of the patients as compared to 75% by the Baveno VII cut-offs. CONCLUSION: A two-step strategy employing lower LSM cut-offs and modeling based on diabetes and AST levels outperforms Baveno VII cut-offs for identifying cACLD in NAFLD patients.

Outcome assessment of biliary stricture repair following cholecystectomy in a tertiary care centre.

PURPOSE: Bile duct injuries (BDIs) are the potential grievous complications of cholecystectomy that result in substantial morbidity and mortality. Outcomes of BDI management depend on multiple factors such as the type and extent of injury, timing of repair, and surgical expertise. The present retrospective study was conducted to analyse the risk factors associated with the BDI repair outcomes. METHODS: The data of patients having primary or recurrent bile duct stricture following BDI from 1985 to 2018 were retrospectively evaluated. RESULTS: A total of 268 patients underwent hepaticojejunostomy (HJ). Of the total, 218 patients had primary bile duct stricture, and 50 patients had HJ stricture. The most commonly performed procedure for primary BDI was Roux-en-Y HJ (RYHJ), followed by right hepatectomy, right posterior sectionectomy, and left hepatectomy. All patients with strictured HJ underwent RYHJ, except one who underwent a right hepatectomy. Outcome assessment using the McDonald grading system showed that 62%, 27%, 5%, and 6% of patients with primary bile duct stricture had grade A, grade B, grade C, and grade D complications, respectively, with a mortality rate of 3.21%, whereas 46%, 34%, and 18% patients with strictured HJ had grade A, grade B, and grade C complications, respectively, with a mortality rate of 2%. High-up biliary strictures, early repair, and blood loss > 350 mL are the surrogate markers for failure of repair. CONCLUSION: Management of BDI needs a multidisciplinary approach. The outcomes of both primary biliary stricture and strictured HJ can be improved with management of patients in a tertiary care centre. However, attempts to repair within 2 weeks of injury, Strasberg E4 and E5, and blood loss of > 350 mL may have an adverse effect on the outcome of HJ.

Monotherapy with thiopurines in stricturing Crohn's disease: A real-life experience from low- and middle-income countries.

BACKGROUND: Stricturing Crohn's disease (CD) is difficult to manage medically with limited treatment options, anti-tumor necrosis factor (TNF) therapy being the first-line therapy. Although thiopurines are also recommended first-line treatment option for maintenance of remission in steroid-dependent CD, evidence on their use in stricturing CD is lacking. We evaluated the efficacy of azathioprine (AZA) in patients with stricturing CD. METHODS: In this retrospective cohort study (January 2005 to July 2020), patients with stricturing CD who were managed with AZA as a primary therapy for at least 6 months, and had a follow-up of at least 6 months after AZA initiation were included. Disease characteristics, complications, long-term response, and adverse events were noted. RESULTS: One hundred and fifteen patients were included (mean age 33.8±14 years, 67.8% males, median disease duration 98 months [IQR: 60-158], median follow-up duration 60 months [IQR: 50-96]). 46.1% (n=53) patients had significant anemia at presentation, and 73% (n=84) had isolated small bowel involvement. Median dose of AZA was 100 mg (equivalent to 1.5 mg/kg). Median therapy and follow-up duration (after AZA initiation) was 17 (IQR: 9-42) and 33 months (IQR 18-60), respectively. The cumulative probability of maintaining response without treatment failure at 1, 2, and 5 years was 73.1%, 40.7%, and 18.5%, respectively. Among patients with AZA failure, 15.6% received methotrexate, 13% received anti-TNFs, and 9.5% underwent surgery. Significant anemia (<10 g/dL) at presentation and steroid dependence predicted AZA failure. 31.3% patients experienced adverse events, commonest being leukopenia (n=29, 25.2%). CONCLUSION: Azathioprine demonstrated good short-term and modest long-term response rates in patients with stricturing CD.

Clinicopathological profile and outcomes of anorectal melanoma from a tertiary care center in India.

Background: Anorectal melanoma (AM) is a rare subtype of melanoma. Aim: To study the clinic-pathologic features and outcomes in patients with AM. Materials & methods: Clinical, pathologic findings and outcomes of patients with AM were recorded. Results: Twenty-seven patients with AM were identified with median age of 57 years. Most patients presented in stage III (44.4%). Lymph node involvement was seen in 70.4%. The response to chemotherapy and immunotherapy was 16.6 and 25.0%, respectively. At a median follow up of 11 months, median overall survival was 30 months. Ballantine stage 3 and weight loss at presentation were predictors of poor survival. Conclusion: AM presents at an advanced stage with lymph node and distant metastasis.

Prospective validation of AIIMS index as a predictor of steroid failure in patients with acute severe ulcerative colitis.

BACKGROUND: Optimal outcomes in acute severe ulcerative colitis (ASUC) are related to time-bound management based upon early prediction of response to intravenous (IV) steroids. In an earlier study, we described the All India Institute of Medical Sciences (AIIMS) index (baseline Ulcerative Colitis Endoscopic Index of Severity [UCEIS] ≥ 7 and day 3 fecal calprotectin [FCP] > 1000 µg/g) for predicting failure of IV steroids. The current study is designed to validate this index in a prospective cohort. METHODS: IV steroid-naïve patients with ASUC, satisfying Truelove and Witts' criteria, hospitalized from August 2018 to July 2019 were included. Patients' assessment included baseline sigmoidoscopy, day 1 and 3 FCP, hemogram, biochemistry and day 3 C-reactive protein. All patients received IV steroids, and the primary outcome was steroid failure, defined as the need for colectomy or rescue therapy with cyclosporine (CYC)/infliximab (IFX) during admission. RESULTS: Of the 47 patients, eight were excluded (four received steroids outside, two were directly taken for surgery/infliximab therapy, one had toxic megacolon, and one had infectious colitis), and 39 patients were included (mean age: 36.1 ± 12.6 years, male: 31%). Fifteen patients (38%) failed IV steroid and required rescue therapy (IFX: 9, CYC: 2, Colectomy: 3, IFX followed by colectomy: 1). On univariate analysis, UCEIS ≥ 7 at baseline (p = 0.006), day 1 FCP (p = 0.03), day 3 FCP > 1000 µg/g (p = 0.001), Oxford criteria (p = 0.04) and AIIMS index (p < 0.001) were significantly different between steroid responders and steroid failures. On multivariate analysis, day 3 FCP > 1000 µg/g (odds ratio (odds ratio (OR)= 6.4;(95% CI =2.2-196.1) and baseline UCEIS ≥ 7 (OR) = 10.1;(95% CI = 2.1-80.2) were independent predictors. The AIIMS index predicted steroid failure with a better specificity (100% vs. 83%, p = 0.04) and positive predictive value (100% vs. 64%, p = 0.03) than Oxford criteria. CONCLUSION: AIIMS index has been validated in 39 prospective ASUC patients as an effective early predictor of steroid failure (sensitivity = 53%, specificity = 100%).

Real world analysis on the efficacy and safety of anti-tumor necrosis factor therapy in patients with stricturing Crohn's disease.

Crohn's disease (CD) is often complicated by strictures and associated with increased risk for surgery. Inflammatory strictures respond to medical therapy, and anti-tumor necrosis factor (TNF) therapy is often used after the failure of steroids. However, data on efficacy of anti-TNF therapy in stricturing CD is limited. We retrospectively analysed the records of patients with stricturing CD who were treated with anti-TNF therapy and were prospectively followed from January 2005 to July 2020. Treatment success was defined as continuation of anti-TNF without the requirement for steroids or parenteral nutrition, switch to other anti-TNF, endoscopic dilation, surgery and severe adverse events leading to the withdrawal of anti-TNF. Fifty-nine patients were included [50-infliximab, 9-adalimumab; mean age-30.1 ± 15 years; males-69.5%; median disease duration-124 (range 30-396) months; median follow-up duration-42 (range 8-180) months]. Ileum was the most common site of stricture (69.5%), 20.3% of patients had colonic strictures, and 64.4% had multiple strictures. 55.9% of patients were steroid dependent and 37.3% were steroid refractory. The median duration of anti-TNF therapy was 14 (range 2-96) months, and 54.2% (n = 32) patients received concomitant immunomodulators. 88% improved with induction (11.8% primary non-response), secondary loss of response was seen in 52.2%, and the cumulative probability of treatment success at 1, 2 and 5 years was 69%, 51%, and 28% respectively. Anaemia at presentation predicted poor response. Only 30% of patients retained biologics on long-term (lack of response, cost, adverse events). 16.9% had adverse events, the commonest being reactivation of tuberculosis (5.1%). Anti-TNF therapy is associated with good short-term treatment success with modest long-term response in stricturing CD.

Mutations in two component system (PhoPQ and PmrAB) in colistin resistant Klebsiella pneumoniae from North Indian tertiary care hospital.

Colistin resistance in Gram negative bacteria is mainly attributed to chromosomal mutations in Two Component Systems(TCS) PhoPQ and PmrAB and plasmid-borne genes(mcr and its variants). The aim of this study was to understand the molecular basis of colistin resistance in Klebsiella pneumoniae and determine clonal transmission, in a North Indian tertiary care hospital over a 2.5 year period. Antimicrobial susceptibility was determined by Vitek and colistin resistance was confirmed by broth microdilution. Carbapenemases(blaKPC, blaVIM, blaIMP, blaNDM, blaOXA-48) and mcr-1 screening was done by PCR. Mutations in chromosomal genes mgrB, phoP, phoQ, pmrA, pmrB were analysed. Sequence typing was performed by Multilocus sequence typing(MLST). OXA-48 was detected in thirteen isolates while three isolates co-expressed OXA-48 and NDM. The mcr-1 gene was absent in all 16 isolates. Deleterious mutations in mgrB included insertion sequences IS903 and ISkpn26 and a premature stop codon. A total of 18 point mutations were identified in PhoPQ and PmrAB TCS; of which, novel mutations were reported in phoQ (K46E, L322V, D152N, F373L, R249G), pmrB (P159R) and pmrA (D149L). Six different sequence types ST231, ST147, ST395, ST42, ST14 and ST101 were identified. Phylogenetic analysis showed that sequence types ST14, ST395 and ST147 are closely related to ST101 and all identified sequence types had a common ancestor ST231. Colistin resistance in K. pneumoniae was attributed to mutations in PhoPQ and PmrAB TCS, while location specific distribution of strains indicates clonal transmission. The results of this study will help in formulation of effective infection prevention and antimicrobial development strategies.

Combination of sarcopenia and high visceral fat predict poor outcomes in patients with Crohn's disease.

BACKGROUND: Sarcopenia and visceral fat independently predict poor outcomes in Crohn's disease (CD). However, combined influence of these parameters on outcomes is unknown, and was investigated in the present study. METHODS: This retrospective study evaluated skeletal muscle index (SMI-cross-sectional area of five skeletal muscles normalized for height), visceral and subcutaneous fat area and their ratio (VF/SC) on single-slice computed tomography (CT) images at L3 vertebrae in CD patients (CT done: January 2012-December 2015, patients followed till December 2019). Sarcopenia was defined as SMI < 36.5 cm2/m2 and 30.2 cm2/m2 for males and females, respectively. Disease severity, behavior, and long-term outcomes (surgery and disease course) were compared with respect to sarcopenia and VF/SC ratio. RESULTS: Forty-four patients [age at onset: 34.4 ± 14.1 years, median disease duration: 48 (24-95) months, follow-up duration: 32 (12-53.5) months, males: 63.6%] were included. Prevalence of sarcopenia was 43%, more in females, but independent of age, disease severity, behavior and location. More patients with sarcopenia underwent surgery (31.6% vs 4%, p = 0.01). VF/SC was significantly higher in patients who underwent surgery (1.76 + 1.31 vs 0.9 + 0.41, p = 0.002), and a cutoff of 0.88 could predict surgery with sensitivity and specificity of 71% and 65% respectively. On survival analysis, probability of remaining free of surgery was lower in patients with sarcopenia (59.6% vs 94.1% p = 0.01) and those with VF/SC > 0.88 (66.1% vs 91.1%, p = 0.1), and still lower in those with both sarcopenia and VF/SC > 0.88 than those with either or none (38% vs 82% vs 100%, p = 0.01). CONCLUSIONS: Combination of sarcopenia and high visceral fat predict worse outcomes in CD than either.

Randomised clinical trial: exclusive enteral nutrition versus standard of care for acute severe ulcerative colitis.

BACKGROUND: Intravenous corticosteroids are the mainstay of therapy for acute severe ulcerative colitis (ASUC), but 30%-40% of patients fail to respond. AIM: To investigate the effectiveness of exclusive enteral nutrition (EEN) as adjunctive therapy to intravenous corticosteroids in patients with ASUC. METHODS: This was an open-label randomised controlled trial, in which patients who were admitted with ASUC between August 2018 and May 2020 were randomised 1:1 to EEN or standard of care (SOC). Patients on EEN received a semi-elemental formula for 7 days along with SOC. The primary outcome was corticosteroid failure, defined by the need for salvage medical therapy or colectomy. Faecal microbial analysis was performed on day 1 and day 7 by 16s ribosomal RNA sequencing in some patients. RESULTS: Of 62 patients (mean age 35.3 ± 12.1 years, 40% male), 32 were randomised to EEN and 30 to SOC. Corticosteroid failure was lower on EEN compared to SOC (intention-to-treat analysis 25% vs 43%, P = 0.051; per protocol analysis 19% vs 43%, P = 0.04), without any difference in colectomy rate (9% vs 13%; P = 0.41). Patients on EEN had a shorter hospital stay [median (range) 10 (8-17) vs 13 (8-24) days; P = 0.04], higher day 7 albumin level (34 ± 4 vs 29 ± 3 g/L, P < 0.01), greater reduction in serum C-reactive protein and faecal calprotectin levels (both P = 0.04) and a lower composite outcome of colectomy/hospitalisation at 6 months (16% vs 39%; P = 0.045) compared to SOC. Patients on EEN showed increased abundance of Erysipelotrichaceae on day 7, with reduced Bifidobacterium and Veillonellaceae compared to SOC. CONCLUSIONS: EEN for 7 days may augment corticosteroid responsiveness in patients with ASUC. (REF/2018/05/019844; CTRI/2020/06/025989).

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

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.

Relapse rate following withdrawal of anti-TNF therapy in patients with inflammatory bowel disease: A real-life cohort from northern India.

BACKGROUND: The decision to withdraw anti-tumor necrosis factor (anti-TNF) therapy in patients with inflammatory bowel disease (IBD) remains controversial, especially in the developing world, where its long-term use is restrained by side effects and prohibitive cost. Present study evaluated the relapse rate and its predictors following anti-TNF withdrawal in a cohort of IBD patients from northern India. METHODS: Patients with IBD who received anti-TNF therapy (induction and beyond), and were under follow-up at All India Institute of Medical Sciences, New Delhi, from January 2005 to July 2018 were included. Demographic features, disease characteristics, duration, response to anti-TNF therapy, and relapse rate after its withdrawal were analyzed. RESULTS: Among 4600 patients with IBD under follow-up, 90 (1.9%) received anti-TNF therapy, of whom 11 were excluded (8-complete records unavailable; 3-received only single dose). Of 79 patients (mean age-40.1 ± 14.2 years; 53.2% males; 31 [39.2%] ulcerative colitis, 47 [59.5%] Crohn's disease; median follow-up-24 [12-39] months), 9 (11.4%) were primary non-responders, 19 (24.1%) had secondary loss of response, and 51 (64.5%) maintained clinical response on anti-TNF. Anti-TNF was withdrawn in 45 (57%) patients (major causes: financial burden-16.5%; tubercular reactivation-12.7%), of whom 33 were in clinical remission. Over a median follow-up of 26 (7.5-45) months, 15 patients (45.5%) relapsed. Most of them responded to antibiotics, steroids, or anti-TNF agents; only 3 required surgery. On Kaplan-Meier analysis, long disease duration prior to therapy was a significant predictor of relapse (hazard ratio [HR] = 1.33, p = 0.034). CONCLUSION: Almost 50% patients with IBD in clinical remission relapse within a year of anti-TNF withdrawal. However, most of these patients have a favorable disease course and respond to medical therapy.

Expression and Clinical Implications of Cysteine Cathepsins in Gallbladder Carcinoma.

Background: Gallbladder carcinoma (GBC) exhibits poor prognosis due to its detection at an advanced stage. Upregulation of lysosomal cysteine proteases cathepsin L (CTSL) and cathepsin B (CTSB) has been implicated in several tumorigenic processes. However, no such information in GBC was available. Therefore, the present study was planned to investigate the expression and clinical significance of these cathepsins in GBC. Methods: Activities of CTSL and CTSB were assayed in the gallbladder (GB) tissues obtained from GBC patients (n = 43) and control subjects (n = 69). Protein and mRNA levels were quantified using immunohistochemistry and real-time PCR (qPCR), respectively. Finally, serum levels of CTSL and CTSB were estimated by ELISA. Receiver operating characteristic (ROC) curve analysis was used for the assessment of sensitivity, specificity, and diagnostic accuracy of these cysteine cathepsins in GBC. The association of combined CTSL and CTSB activity with overall survival was assessed using Kaplan Meier survival analysis. Results: The expression and activity of both CTSL and CTSB were significantly increased (p < 0.050) in tumors of GBC patients as compared to controls. Enzymatic activity of CTSL+B and CTSB exhibited a strong positive association with tumor stage and lymph node involvement in GBC (p < 0.050). Interestingly, the elevated activity of combined CTSL+B was also associated with increased mortality in these patients. Furthermore, significantly enhanced levels of serum CTSL and CTSB were also observed in GBC (p < 0.050) as compared to controls. ROC analysis revealed high diagnostic significance of serum CTSB and CTSL for distinguishing GBC patients from controls with an area under the curve (AUC) of 82 and 77%, respectively. Conclusion: This study, for the first time, demonstrates the clinical significance of CTSL and CTSB overexpression in GBC. Our findings may help improve the clinical management of this carcinoma.

Carbapenem resistance in Escherichia coli and Klebsiella pneumoniae among Indian and international patients in North India.

The aim of the study was to find out the carbapenem resistance rate and prevalence of different carbapenemase genes in Klebsiella pneumoniae and Escherichia coli from a North Indian corporate hospital that receives both Indian and international patients. A total of 528 clinical isolates of E. coli and K. pneumoniae were included in the study. All isolates that were found resistant to carbapenems by MIC testing (Vitek II Compact®) were screened for NDM, OXA-48, VIM, and KPC genes by PCR. Sequencing of NDM gene and transmissibility by conjugation assay were checked on 22 randomly selected NDM-positive isolates. One hundred and fifty-six isolates (29.54%) were carbapenem-resistant. The rate of carbapenem resistance was significantly higher in K. pneumoniae as compared to E. coli (53.9% vs. 15.6%; p < 0.05). The NDM gene was found in 34.6% (54/156), OXA-48 in 31.4% (49/156), co-expression of NDM + OXA-48 in 15.3% (24/156) of the carbapenem-resistant isolates. VIM and KPC were absent in all isolates. NDM gene was significantly more prevalent in E. coli than K. pneumoniae (p < 0.05). All the tested isolates formed transconjugants and NDM-5 was the most common variant in both species (15/22). The presence of plasmid-based NDM calls for stricter surveillance measures in our hospital settings.

Gastrointestinal Stromal Tumor of the Jejunum With Active Bleeding Demonstrated on Dual-Energy MDCT Angiography: A Case Report.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract and may occasionally present with acute gastrointestinal bleed (GIB). Multidetector computed tomography (MDCT) angiography is extremely useful in demonstrating the tumor as well as the presence of active hemorrhage, thereby guiding subsequent interventional or surgical management. We report a case of a 38-year-old man who presented with acute-onset melena and compensated shock, whose source of bleed remained elusive on endoscopy. MDCT angiography performed on a dual-energy scanner showed a jejunal tumor with active intraluminal contrast extravasation. The tumor was subsequently resected and the patient did well on follow-up. This was one of the few instances when MDCT angiography demonstrated active bleeding in a GIST and the first such case demonstrated on a dual-energy scanner.