Coconut Water Induces Clinical Remission in Mild to Moderate Ulcerative Colitis: Double-blind Placebo-controlled Trial.

BACKGROUND & AIMS: Coconut water (CW) is anti-inflammatory, can manipulate the gut microbiome, and is a rich source of potassium. Gut microbiome modulation improves outcomes in ulcerative colitis (UC), and potassium possesses in vitro anti-inflammatory property. We evaluated the effect of CW as an adjunct therapy for patients with mild-moderate UC. METHODS: This single-center, double-blind, placebo-controlled trial randomized patients with mild to moderate (Simple Clinical Colitis Activity Index [SCCAI]: 3-9) endoscopically active UC (Ulcerative Colitis Endoscopic Index of Severity [UCEIS] >1) in 1:1 ratio to CW + standard medical therapy (SMT) vs placebo + SMT. Four hundred mL of CW was administered for 8 weeks. Primary outcome measure was clinical remission (SCCAI ≤2), and secondary outcome measures were clinical response (SCCAI decline ≥3) and adverse events at 8 weeks. Microbiome was analyzed at baseline and 8 weeks. RESULTS: Of 121 patients screened, 95 were included for modified intention to treat analysis (CW, n = 49; placebo, n = 46) (mean age, 37.2 ± 11.2 years; males, 54.1%; disease duration, 48 months [interquartile range (IQR), 24-90 months]; pancolitis, 26.1%; SCCAI, 5 [IQR, 4-6]; UCEIS, 4 [IQR, 3-5]). Clinical response (57.1% vs 28.3%; odds ratio [OR], 3.4; 95% confidence interval [CI], 1.4-7.9; P = .01), remission (53.1% vs 28.3%; OR, 2.9; 95% CI, 1.2-6.7; P = .02), and proportion of patients with fecal calprotectin (FCP) <150 µg/g (30.6% vs 6.5%; OR, 6.3; 95% CI, 1.7-23.6; P = .003) were significantly higher in CW. The relative abundance of bacterial taxa that had a significant or trend towards negative correlation with SCCAI, UCEIS, or FCP increased at 8 weeks in CW, and this effect was independent of disease activity and dietary fiber. Adverse events were comparable, and no patient developed hyperkalemia. CONCLUSIONS: CW was more effective than placebo for induction of clinical remission in patients with mild to moderate UC. The trial was prospectively registered on Clinical Trials Registry of India (ctri.nic.in, Number: CTRI/2019/03/01827).

Ten missteps in the management of inflammatory bowel disease in Asia: An expert report by the Asian Pacific Association of Gastroenterology Working Group on Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is rapidly emerging in the Asia Pacific region. However, there are many challenges in the diagnosis and management of this condition. The Asian Pacific Association of Gastroenterology (APAGE) Working Group on IBD conducted a round table meeting to identify 10 common mistakes in the management of IBD in Asia. To summarize, many physicians still over rely on a definitive histological diagnosis before starting treatment and do not fully establish disease extent such as perianal and proximal gastrointestinal involvement in Crohn's disease (CD) or extent of involvement in ulcerative colitis (UC). It is also essential to actively look for evidence of extra-intestinal manifestations, which may influence choice of therapy. In terms of conventional therapy, underuse of topical 5 aminosalicylates (5-ASAs) in UC and inappropriate dosing of corticosteroids are also important considerations. Acute severe UC remains a life-threatening condition and delay in starting rescue therapy after inadequate response to intravenous steroids is still common. Anti-tumor necrosis factors should be considered first line in all cases of complex perianal fistulizing CD. Most patients with IBD are on potent immunosuppressive therapy and should be screened for latent infections and offered vaccinations according to guidelines. Under-recognition and management of significant complications such as anemia, osteoporosis, malnutrition, and thromboembolism should also be addressed. Colonoscopy is still not properly performed for dysplasia/cancer surveillance and for evaluating post-op recurrence of CD. Another common misstep is inappropriate withdrawal of medications during pregnancy leading to increased complications for the mother and the newborn.

Long-term Gastrointestinal Sequelae Following COVID-19: A Prospective Follow-up Cohort Study.

BACKGROUND & AIMS: Coronavirus disease 2019 (COVID-19) is associated with long-term gastrointestinal sequelae; however, prospective longitudinal data are sparse. We prospectively studied the frequency, spectrum, and risk factors of post infection functional gastrointestinal disorders/disorders of gut-brain interaction (PI-FGID/DGBI) after COVID-19. METHODS: Three hundred twenty cases with COVID-19 and 2 control groups, group A, 320 healthy spouses/family controls, and group B, 280 healthy COVID serology-negative controls, were prospectively followed up at 1, 3, and 6 months by using validated Rome IV criteria to evaluate the frequency of PI-FGID/DGBI. RESULTS: Of 320 cases, at 1 month 36 (11.3%) developed FGID symptoms. Persistent symptoms were noted in 27 (8.4%) at 3 months and in 21 (6.6%) at 6 months. At 3 months, 8 (2.5%) had irritable bowel syndrome, 7 (2.2%) had functional diarrhea, 6 (1.9%) had functional dyspepsia, 3 (0.9%) had functional constipation, 2 (0.6%) had functional dyspepsia-IBS overlap, and 1 (0.3%) had functional abdominal bloating/distention. Among symptomatic individuals at 3 months, 8 (29.6%) were positive for isolated carbohydrate malabsorption, 1 (3.7%) was positive for post infection malabsorption syndrome, and 1 (3.7%) was positive for intestinal methanogen overgrowth. None of the healthy controls developed FGID up to 6 months of follow-up (P < .01). Predictive factors at 3 and 6 months were severity of infection (P < .01) and presence of gastrointestinal symptoms at the time of infection (P < .01). CONCLUSIONS: COVID-19 led to significantly higher number of new onset PI-FGID/DGBI compared with healthy controls at 3 and 6 months of follow-up. If further investigated, some patients can be diagnosed with underlying malabsorption.

Revised Algorithmic Approach to Differentiate Between Nonspecific and Specific Etiologies of Chronic Terminal Ileitis.

INTRODUCTION: Chronic isolated terminal ileitis (TI) may be seen in Crohn's disease (CD) and intestinal tuberculosis (ITB) in addition to other etiologies that may be managed symptomatically. We developed a revised algorithm to distinguish patients with a specific etiology from a nonspecific etiology. METHODS: Patients with chronic isolated TI followed up from 2007 to 2022 were retrospectively reviewed. A specific (ITB or CD) diagnosis was made based on standardized criteria, and other relevant data were collected. Using this cohort, validation of a previously suggested algorithm was conducted. Furthermore, based on the results of a univariate analysis, a multivariate analysis with bootstrap validation was used to develop a revised algorithm. RESULTS: We included 153 patients (mean age 36.9 ± 14.6 years, males-70%, median duration-1.5 years, range: 0-20 years) with chronic isolated TI of whom 109 (71.2%) received a specific diagnosis (CD-69, ITB-40). On multivariate regression and validation statistics with a combination of clinical, laboratory, radiological, and colonoscopic findings, an optimism corrected c-statistic of 0.975 and 0.958 was obtained with and without histopathological findings, respectively. Revised algorithm, based on these, showed sensitivity, specificity, positive and negative predictive values, and overall accuracy of 98.2% (95% CI: 93.5-99.8), 75.0% (95% CI: 59.7-86.8), 90.7% (95% CI: 85.4-94.2), 94.3% (95% CI: 80.5-98.5) and 91.5%(95% CI:85.9-95.4), respectively. This was more sensitive and specific than the previous algorithm (accuracy 83.9%, sensitivity 95.5%, and specificity 54.6%). DISCUSSION: We developed a revised algorithm and a multimodality approach to stratify patients with chronic isolated TI into specific and nonspecific etiologies with an excellent diagnostic accuracy, which could potentially avoid missed diagnosis and unnecessary side effects of treatment.

Faecal microbiota transplantation with anti-inflammatory diet (FMT-AID) followed by anti-inflammatory diet alone is effective in inducing and maintaining remission over 1 year in mild to moderate ulcerative colitis: a randomised controlled trial.

OBJECTIVE: Microbiome and dietary manipulation therapies are being explored for treating ulcerative colitis (UC). We aimed to examine the efficacy of multidonor faecal microbiota transplantation (FMT) and anti-inflammatory diet in inducing remission followed by long-term maintenance with anti-inflammatory diet in patients with mild-moderate UC. DESIGN: This open-labelled randomised controlled trial (RCT) randomised patients with mild-moderate (Simple Clinical Colitis Activity Index (SCCAI) 3-9) endoscopically active UC (Ulcerative Colitis Endoscopic Index of Severity (UCEIS)>1) on stable baseline medications in 1:1 ratio to FMT and anti-inflammatory diet (FMT-AID) versus optimised standard medical therapy (SMT). The FMT-AID arm received seven weekly colonoscopic infusions of freshly prepared FMT from multiple rural donors(weeks 0-6) with anti-inflammatory diet. Baseline medications were optimised in the SMT arm. Clinical responders (decline in SCCAI>3) at 8 weeks in both arms were followed until 48 weeks on baseline medications (with anti-inflammatory diet in the FMT-AID arm). Primary outcome measures were clinical response and deep remission (clinical-SCCAI <2; and endoscopic-UCEIS <1) at 8 weeks, and deep remission and steroid-free clinical remission at 48 weeks. RESULTS: Of the 113 patients screened, 73 were randomised, and 66 were included in (35-FMT-AID; 31-SMT) modified intention-to-treat analysis (age-35.7±11.1 years; male-60.1%; disease duration-48 (IQR 24-84) months; pancolitis-34.8%; SCCAI-6 (IQR 5-7); UCEIS-4 (IQR 3-5)). Baseline characteristics were comparable. FMT-AID was superior to SMT in inducing clinical response (23/35 (65.7%) vs 11/31 (35.5%), p=0.01, OR 3.5 (95% CI 1.3 to 9.6)), remission (21/35 (60%) vs 10/31 (32.3%), p=0.02, OR 3.2 (95% CI 1.1 to 8.7)) and deep remission (12/33 (36.4%) vs 2/23 (8.7%), p=0.03, OR 6.0 (95% CI 1.2 to 30.2)) at 8 weeks. Anti-inflammatory diet was superior to SMT in maintaining deep remission until 48 weeks (6/24 (25%) vs 0/27, p=0.007). CONCLUSION: Multidonor FMT with anti-inflammatory diet effectively induced deep remission in mild-moderate UC which was sustained with anti-inflammatory diet over 1 year. TRIAL REGISTRATION NUMBER: ISRCTN15475780.

Relapse rates after withdrawal of thiopurines in patients with inflammatory bowel disease.

PURPOSE: Withdrawal of thiopurines after remission is associated with an increased risk of relapse in patients with inflammatory bowel disease (IBD). However, long-term data on thiopurine withdrawal is limited, especially from developing countries where the cost of long-term therapy poses a significant burden on patients. METHODS: Patients with IBD on thiopurine monotherapy for ≥ 4 months, who stopped thiopurines while in clinical remission and were not on any other immunomodulator or biologics at the time of withdrawal, were included in this retrospective analysis. RESULTS: Among 1093 patients with IBD on thiopurine monotherapy, 461 patients stopped thiopurine due to various reasons. Among these, 218 (ulcerative colitis (UC) = 179; Crohn's disease (CD) = 39) patients were in clinical remission and were continued on mesalamine. Overall, 36.7% (n = 80) relapsed after a median duration of 20 months (IQR: 9-49). Relapse rate was higher in UC than CD (39.7% vs 23%, p = 0.055). Cumulative probabilities of relapse were 17%, 34%, and 44% at the end of 1, 3, and 5 years, respectively. The relapse rate at 5 years was significantly lower in patients who had stopped azathioprine after 4 years of therapy (31% vs 54%, p = 0.007). On multi-variate cox regression analysis, male sex [HR: 1.6(1.0-2.6), p = 0.02] and short duration of therapy with thiopurines [HR: 1.02 (1.01-1.02), p = 0.004] before withdrawal were associated with increased risk of relapse. CONCLUSION: Approximately 50% patients with IBD in remission would relapse after 5 years of thiopurine withdrawal. Male sex and shorter treatment duration predict relapse. Treatment should be continued in patients who tolerate and maintain remission on long-term thiopurine.

Minimal risk of lymphoma and non-melanoma skin cancer despite long-term use of thiopurines in patients with inflammatory bowel disease: A longitudinal cohort analysis from northern India.

BACKGROUND AND AIM: Thiopurines are widely used to maintain remission in both ulcerative colitis (UC) and Crohn's disease (CD). Reported effectiveness and tolerability rates have been variable across studies. There are only sparse data in Asian population regarding the long-term efficacy and safety of thiopurines. METHODS: Records of 5351 patients followed up at inflammatory bowel disease (IBD) clinic, All India Institute of Medical Sciences, New Delhi from 2004 to 2020 were evaluated retrospectively. Safety was evaluated in terms of long-term adverse events and development of malignancy. RESULTS: Of 5351 patients with IBD, 1093 who received thiopurine for > 3 months (UC = 788 [proctitis-1.9%, left-sided colitis-44.9%, & pancolitis-53.1%] & CD = 305 [inflammatory-42.6%, stricturing-46.9%, & fistulizing-10.5%]) were included (60.8%-male patients). Follow up and treatment duration on thiopurine were 7 (4-12) years and 39.4 ± 40.3 months, respectively, with 254 (23.2%) patients receiving thiopurines for more than 5 and 68 (6.2%) receiving for more than 10 years. Three hundred and fifty-nine (UC: 249 [31.6%]; CD: 110 [36.1%]; P = 0.1) patients developed adverse events; commonest was myelosuppression (23.4%) followed by gastrointestinal intolerance (3%), flu-like illness (1.7%), and arthralgia/myalgia (1.4%). Myelosuppression was the commonest cause of thiopurine withdrawal. No patient (including 254 patients on thiopurine for ≥ 5 years) developed lymphoma or non-melanoma skin cancer. The cumulative probability of staying free from adverse events in overall IBD cohort at 1, 2, and 5 years was 78.6%, 71.9%, and 68.4%, respectively, and this was comparable between UC and CD (P = 0.09). CONCLUSION: Long-term follow up of patients with IBD from northern India on thiopurine monotherapy demonstrated minimal risk of development of lymphoma as well as non-melanoma skin cancer.

Double-Sided, Omnidirectional γ-AlOOH Hierarchical Nanostructures: Imparting Enhanced Antireflective Properties with Self-Cleaning Capacity for Optical Devices.

Herein, we have successfully developed an integrated strategy to develop antireflective coatings with self-cleaning capabilities based on periodic double-sided photonic γ-AlOOH nanostructures to transmit maximum incident light photons. Interfacial reflections are instinctive and one of the fundamental phenomena occurring at interfaces owing to refractive index mismatch. The eradication of such undesirable light reflection is of significant consideration in many optical devices. A systematic approach was carried out to eradicate surface reflection and enhance optical transmission by tailored γ-AlOOH nanostructures. The γ-AlOOH photonic nanostructures with subwavelength features exhibited a gradient index, which almost eliminated the refractive index mismatch at the interface. Optical transmittance of 97% was achieved in the range of 350-800 nm at normal incidence compared to uncoated glass (89%). A multilayer model approach was adopted to extract the effective refractive index of the coating, which showed a graded index from the top to the bottom surface. Further, to fully comprehend the optics of these nanostructures, the omnidirectional (20-70°) antireflective property has been explored using variable-angle specular reflectance spectroscopy. The hierarchical γ-AlOOH nanostructures exhibited only ∼1.3% reflectance at the lower incident angle in the visible spectra and an average reflectance of ∼7.6% up to an incident angle of 70°. Moreover, the hierarchical nanostructures manifested contact angle (CA) >172° and roll-off angle (RA) <1° with excellent self-cleaning performance. Furthermore, the abrasion resistance of the coating is discussed in detail, which displayed a good resistance against sand erosion. Significantly, the photovoltaic performance of the coated modules exhibited a relative enhancement of ∼17% in efficiency, which is attributed to the efficient coupling of light rays. Thus, the integration of the antireflection (AR) property with self-cleaning ability can provide a cost-effective energy solution for optoelectronic devices, display devices, and thin-film optics.

FibroScan-aspartate aminotransferase score in an Asian cohort of non-alcoholic fatty liver disease and its utility in predicting histological resolution with bariatric surgery.

BACKGROUND AND AIM: The FibroScan-aspartate aminotransferase (FAST) score was developed for identifying patients with non-alcoholic steatohepatitis, who also have an elevated non-alcoholic fatty liver disease (NAFLD) activity score (NAS) ≥ 4 and significant fibrosis (F ≥ 2). We aimed to validate it in our NAFLD cohort and assess if it correlates with the histological changes after bariatric surgery. METHODS: Patients with NAFLD, including those undergoing bariatric surgery, were included. The FAST score was calculated using liver stiffness measure, controlled attenuation parameter, and aspartate aminotransferase. Calibration and discrimination of the model were assessed by calibration plots and area under the receiver operating characteristic curve, respectively. Sensitivity and specificity were assessed at the rule-out and rule-in cutoffs (≤0.35 and ≥0.67), respectively. Changes in the NAS and FAST scores were compared in the bariatric cohort 1 year after surgery. RESULTS: The cohort composed of 309 patients, of which 48 patients underwent repeat liver biopsy at 1 year. The model showed good discrimination with area under the receiver operating characteristic curve of 0.79 (0.74-0.84); however, it was not satisfactorily calibrated (Hosmer-Lemeshow test, P = 0.008). The sensitivity and specificity at the rule-out and rule-in cutoffs were 0.90 and 0.84, respectively. A significant correlation was seen between the 1-year reduction in the NAS and FAST scores (r = 0.38, P = 0.009). A significant reduction in the median FAST score was seen in patients who had ≥2-point reduction in NAS after bariatric surgery. CONCLUSION: FibroScan-aspartate aminotransferase score demonstrated good discrimination for fibrotic non-alcoholic steatohepatitis in our cohort. However, a miscalibration resulted in overprediction. The score correlated well with the histological response to interventions for NAFLD.

Evolution of Temperature-Driven Interfacial Wettability and Surface Energy Properties on Hierarchically Structured Porous Superhydrophobic Pseudoboehmite Thin Films.

Interaction of water on heterogeneous nonwetting interfaces has fascinated researchers' attention for wider applications. Herein, we report the evolution of hierarchical micro-/nanostructures on superhydrophobic pseudoboehmite surfaces created from amorphous Al2O3 films and unraveled their temperature-driven wettability and surface energy properties. The influence of hot water immersion temperature on the dissolution-reprecipitation mechanism and the surface geometry of the Al2O3 film have been extensively analyzed, which helped in attaining the optimal Cassie-Baxter state. The evolution of pseudoboehmite films has been structurally characterized using grazing incidence X-ray diffraction, field-emission scanning electron microscopy, high-resolution transmission electron microscopy, X-ray photoelectron spectroscopy and atomic force microscopy. Interfacial surface energy components on the structured superhydrophobic surface exhibited a very low surface energy of ∼4.6 mN/m at room temperature and ultrahigh water contact angle >175°. The interaction between water droplets on the nonwetting surface was comprehended and correlated to the temperature-dependent surface energy properties. The surface energy and wettability of the structured pseudoboehmite superhydrophobic surface exhibited an inverse behavior as a function of temperature. Interestingly, the superhydrophobic surface exhibited "Leidenfrost effect" below the boiling point of water (67 °C), which is further correlated with the intermolecular forces, interfacial water molecules and surface-terminated groups. These high-temperature wetting transition studies could be potentially valuable for solid-liquid systems working at nonambient temperatures, and also this approach can pave new pathways for better understanding of the solid/liquid interfacial interactions on nanoengineered superhydrophobic surfaces.

Antifungal efficacy of plant essential oils against stored grain fungi of Fusarium spp.

The control potential of seven plant essential oils was evaluated against Fusarium proliferatum (Matsushima) Nirenberg and Fusarium verticillioides Sheldon. The fungicidal activity was assessed through microtiter plate assay to determine the minimum inhibitory and fungicidal concentration of essential oils. The essential oil of Mentha arvensis was adjudged as best for inhibiting the fungal growth, while oil of Thymus vulgaris and Anethum graveolens showed high efficacy in terms of fungicidal activity. The oil of M. arvensis and T. vulgaris also showed good inhibition activity in agar disc diffusion assay. M. arvensis essential oil was analysed for its composition using gas chromatography/mass spectrometry revealing menthol (63.18 %), menthone (15.08 %), isomenthyl acetate (5.50 %) and limonene (4.31 %) as major components. Significant activity of M. arvensis essential oil against F. proliferatum and F. verticillioides isolates obtained, pave the way for its use as antifungal control agents.

Biocontrol potential of essential oil monoterpenes against housefly, Musca domestica (Diptera: Muscidae).

Housefly (Musca domestica L.), one of the most common insects in human settlements, has been associated as vectors for various food-borne pathogens, causing food spoilage and disease transmission. The control of housefly was attempted using plant monoterpenes; menthone, menthol, menthyl acetate, limonene, citral and 1,8-cineole, against different life stages of housefly. Bioefficacy against housefly adults revealed highest repellent activity by menthol (95.6 percent) and menthone (83.3 percent). Against housefly larvae, menthol with an LC90 of 0.02 µl/cm(2) in contact toxicity assay and menthone with a LC90 value of 5.4 µl/L in fumigation assay were found to be most effective control agent. With respect to pupicidal activity, superior performance was shown by menthol, citral and 1,8-cineole in contact toxicity assay and citral and 1,8-cineole in fumigation assay. Limonene was found to be the poorest performer in all the assays. Overall, highest efficacy observed for menthol and menthone in various bioassays was in agreement with the results of essential oil activity obtained previously. Significant activity of monoterpenes against various life stages of housefly demonstrates their potential as excellent insecticides with prospects of monoterpenes being developed into eco-friendly and acceptable products for housefly control.

Thiopurines Have Sustained Long-term Effectiveness in Patients with Inflammatory Bowel Disease, Which is Independent of Disease Duration at Initiation: A Propensity Score Matched Analysis.

BACKGROUND AND AIMS: Thiopurines are viable option for the treatment of inflammatory bowel disease [IBD] in resource-limited countries. However, data on the effect of disease duration at thiopurines initiation on long-term effectiveness are limited. METHOD: We performed a propensity matched analysis of a retrospective cohort of patients with ulcerative colitis [UC] and Crohn's disease [CD]. Patients initiated on thiopurines early in the disease course [≤2 years] were compared with those started late [>2 years]. Effectiveness was defined as no requirement for hospitalisation, anti-tumour necrosis factor [TNF] agents, or surgery, and minimum steroid requirement [≤1 steroid course in 2 years] during follow-up. RESULTS: A total of 988 [UC: 720, CD: 268] patients were included (male: 665 [60.8%], median age: 40 [32-51] years, median follow-up: 40 [19-81] months). Overall effectiveness at 5 and 10 years was 79% and 72% in UC, and 69% and 63% in CD, respectively. After propensity score matching, there was no difference in 5- and 10-year effectiveness between early and late thiopurine initiation groups either for UC [81% and 80% vs 82% and 74%; p = 0.92] or CD [76% and 66% vs 72% and 51%, p = 0.32]. Male sex for UC (negative: hazard ratio [HR]: 0.67, 95% confidence interval [CI): 0.45-0.97; p = 0.03), and ileal involvement [positive: HR: 3.03, 95% CI: 1.32-6.71; p = 0.008], steroid-dependent disease [positive: HR: 2.70, 95% CI: 1.26-5.68; p = 0.01] and adverse events [negative: HR: 0.47, 95% CI:0.27-0.80; p = 0.005] for CD were predictors of thiopurine effectiveness. CONCLUSION: Thiopurines have sustained long-term effectiveness in both UC and CD. However, early thiopurine initiation had no better effect on long-term disease outcome compared with late initiation.

Exclusive Enteral Nutrition Mediates Beneficial Gut Microbiome Enrichment in Acute Severe Colitis.

BACKGROUND: Exclusive enteral nutrition (EEN) supplementation of the standard of care (SOC) augments steroid responsiveness in patients with acute severe ulcerative colitis (ASUC). EEN is known to alter gut microbial composition. The present study investigates EEN-driven gut microbial alterations in patients with ASUC and examines their correlations with clinical parameters. METHODS: Stool samples from patients with ASUC (n = 44) who received either EEN-supplemented SOC (EEN group; n = 20) or SOC alone (SOC group; n = 24) for 7 days were collected at baseline (day 0) and postintervention (day 7). Microbiome analysis was carried out using 16S ribosomal RNA gene sequencing followed by data processing using QIIME2 and R packages. RESULTS: Seven-day EEN-conjugated corticosteroid therapy in patients with ASUC enhanced the abundances of beneficial bacterial genera Faecalibacterium and Veillonella and reduced the abundance of Sphingomonas (generalized linear model fitted with Lasso regularization with robustness of 100%), while no such improvements in gut microbiota were observed in the SOC group. The EEN-associated taxa correlated with the patient's clinical parameters (serum albumin and C-reactive protein levels). Unlike the SOC group, which retained its preintervention core microbiota, EEN contributed Faecalibacterium prausnitzii, a beneficial gut bacterial taxon, to the gut microbial core. EEN responders showed enhancement of Ligilactobacillus and Veillonella and reduction in Prevotella and Granulicatella. Analysis of baseline gut microbiota showed relative enhancement of certain microbial genera being associated with corticosteroid response and baseline clinical parameters and that this signature could conceivably be used as a predictive tool. CONCLUSIONS: Augmentation of clinical response by EEN-conjugated corticosteroid therapy is accompanied by beneficial gut microbial changes in patients with ASUC.

Exclusive enteral nutrition­supplemented corticosteroid therapy in acute severe ulcerative colitis (ASUC) is accompanied by the enrichment of beneficial gut microbial genera, which correlate negatively with the disease activity scores and objective inflammatory markers in ASUC. The baseline gut microbiota in ASUC associates with and may predict corticosteroid response.

A phase I/II clinical trial of ex-vivo expanded human bone marrow derived allogeneic mesenchymal stromal cells in adult patients with perianal fistulizing Crohn's Disease.

BACKGROUND: Perianal fistulas (PF) affect one-third patients with Crohn's disease (CD) with limited therapeutic options. There is dearth of literature on safety and efficacy of bone marrow-derived mesenchymal stromal cells (BMSCs) in this population. METHODS: An open-label, phase I/II, single-arm study was conducted involving local administration of human allogeneic bone marrow-derived mesenchymal stromal cells in perianal fistula of patients with Crohn's disease refractory to standard therapies. Clinical severity and biomarkers were assessed at baseline and periodically until week 104 , and MRI at week 24 and 104. Primary and secondary objectives were to assess safety and efficacy respectively. Fistula remission was complete closure of fistula openings with < 2 cm perianal collection on MRI, and fistula response was decrease in drainage by ≥ 50%. Change in perianal disease activity index, quality-of-life and Van Assche index on MRI over time was assessed using mixed-effect linear regression model. RESULTS: Ten patients (male:8, mean age:27.4 ± 12.0years) were recruited. Self-resolving procedure-related adverse events occurred in three patients, with no follow-up adverse events. In intention to treat analysis at week 24, two patients (20%) achieved fistula remission and seven (70%) had fistula response. At week 52, two (20%) patients were in remission and seven (70%) maintained response. At 104 weeks, two (20%) patients maintained response and one (10%) was in remission. Statistically significant decrease in perianal disease activity index (P = 0.008), Van Assche Index (P = 0.008) and improvement in quality-of-life (P = 0.001) were observed over time. CONCLUSIONS: Allogeneic BMSCs are safe and effective for the treatment of perianal fistulizing CD with significant improvement in clinical severity and radiological healing. TRIAL REGISTRATION: The study was prospectively registered on Clinical trials registry - India (CTRI), CTRI/2020/01/022743 on 14 January 2020, http://ctri.nic.in .

"Prevalence, Predictors, and Impact of Hepatic Steatosis in Patients With Ulcerative Colitis: A Prospective Observational Cohort Study".

Background and Aims: There are no prospective studies evaluating effect of non-alcoholic fatty liver disease (NAFLD) in patients with ulcerative colitis (UC). This prospective observational study assessed the prevalence of NAFLD, its predictors, and its effect on long-term outcomes in UC. Methods: Consecutive UC patients underwent transient elastography, body composition analysis, bone densitometry, anthropometry, and baseline demographic and subjective global assessment. NAFLD was diagnosed by controlled attenuation parameter of >260 dB/m. To evaluate predictors and outcomes, patients of UC with NAFLD (n = 29) were compared with age- and sex-matched patients of UC without NAFLD (n = 27). Results: Among 107 patients of UC (mean age-29 ± 10.6 years; males = 56%, median disease duration-48 [interquartile range: 24-84] months, left sided/pancolitis = 84%), 27% (n = 29) had NAFLD. Patients with body mass index (BMI) > 23 kg/m2 had higher proportion of NAFLD than with normal or low BMI (54.7% [23/42] vs 10% [5/50] vs 6.7% [1/15]). Patients with NAFLD had high BMI (P < 0.001), waist circumference, and fat mass (P < 0.001) but similar fat-free mass (P = 0.798) compared to patients without NAFLD. There was no difference in immunosuppressant and cumulative steroid exposure between two groups. Dietary parameters including daily energy, protein, fat, and carbohydrate intake were similar between the two groups. On multivariate analysis, high BMI was found to be predictive and low socioeconomic status as a protective factor of NAFLD. On long-term follow-up of three years, there was no difference in steroid, or biologic requirement, disease-related hospitalization, or composite of all three outcomes between two groups. Conclusion: The prevalence of NAFLD was found in nearly a quarter of patients of UC and was affected by metabolic parameters rather than disease activity.

Intravenous albumin infusion does not augment the response rate to a combination of exclusive enteral nutrition and intravenous steroids in acute severe ulcerative colitis: a randomized controlled trial.

INTRODUCTION: 30-40% patients with acute severe ulcerative colitis (ASUC) fail intravenous (IV) steroids requiring medical rescue therapy/colectomy. Low baseline albumin predicts steroid non-response, and exclusive enteral nutrition (EEN) has been shown to improve steroid response and albumin levels. Albumin infusion due to its anti-inflammatory and anti-oxidant properties might further improve steroid response in ASUC, which was evaluated in present study. METHODS: In this open-label randomized controlled trial, patients with ASUC were randomized in 1:1 ratio to albumin + standard of care (SOC) + EEN vs. SOC + EEN (Jan2021 - Feb2023). Both arms received 5 days of EEN with 400 mg IV hydrocortisone/day. Patients in albumin arm were administered 5 days of 20% w/v intravenous albumin (100 ml). Primary outcome was 1) steroid failure (need for rescue medical therapy or colectomy) and 2) proportion of patients with adverse events. RESULTS: Sixty-one patients (albumin-30, SOC-31)(mean age-31.6±0.4 years, male-57.4%), were included. Baseline characteristics were comparable. There was no difference in steroid failure between albumin and SOC arm(10/30(33.33 %) vs 13/31(41.94 %), p=0.49). No adverse events were reported with albumin infusions. Colectomy rate(10% vs 9.68%, P=1), response to salvage medical therapy (88.89% vs 76.92%, P=0.62) and median duration of hospitalization (10.5(7-16) vs 10(7-20), P=0.43) were also comparable. Long-term composite outcome of colectomy and re-admission rates was numerically higher in the albumin than SOC arm (37.04% vs 17.86%, p>0.05), although it did not reach statistical significance. CONCLUSION: There was no benefit of intravenous albumin infusion as an adjunct to IV steroids and EEN in patients with ASUC.

Preparation, characterization, and insecticidal activity evaluation of three different formulations of Beauveria bassiana against Musca domestica.

Three formulations; bait, encapsulation, and emulsion of Beauveria bassiana were prepared and evaluated for their insecticidal activity in simulated field settings. Tea waste-based bait formulation of B. bassiana showed 100% mortality (within 72 h) in lab assay against adult houseflies. In field assay using traps, 65% relative entrapment and 100 % mortality (within 60 h) of entrapped flies was observed. Although the bait formulation was low cost and easy to prepare and transport, its storage ability was limited. Hence, more advanced formulations in form of encapsulation and emulsion was attempted. Encapsulated B. bassiana conidia (using skimmed milk powder, polyvinyl pyrrolidone K-90 and glucose as additives) showed 100% conidial germination and retained 78% conidial viability, even after storage for 12 months at 30 °C. Encapsulated product showed 54.8% (freshly prepared) and 30.6 % (after 12-months storage) mortality of housefly larvae in a simulated field condition. Emulsion formulation was prepared by using Tween 20 as surfactant with seven vegetable oils: soybean, rapeseed, sunflower, olive, castor, til, and linseed. Emulsion with linseed oil showing maximum conidial germination (94%) was evaluated for shelf life and pathogenecity against housefly larvae. Shelf life analysis of emulsion revealed 28% conidial germination and 19.9% housefly larval mortality after 12 months of storage as opposed to 94% conidial germination and 51.7% of larval mortality with fresh product. Significant increase in shelf × targeted application of formulation is expected to increase its mass applicability for housefly control. Also, the variability among products presents diverse opportunities for commercialization.

Housefly (Musca domestica L.) control potential of Cymbopogon citratus Stapf. (Poales: Poaceae) essential oil and monoterpenes (citral and 1,8-cineole).

In spite of being a major vector for several domestic, medical, and veterinary pests, the control aspect of the common housefly, Musca domestica L. (Diptera: Muscidae) is often neglected. In the present study, the essential oil of Cymbopogon citratus and its major components were evaluated for control of housefly. The chemical composition analysis of C. citratus oil by gas chromatographic mass spectrometry (GC-MS) revealed citral (47 %) and 1,8-cineole (7.5 %) as principal components. The analysis of oil vapor by solid phase microextraction (SPME/GC-MS) showed increase in citral (74.9 %) and 1,8-cineole (8.6 %) content. Assay of oil against housefly larvae and pupae through contact toxicity assay showed lethal concentration (LC)(50) value of 0.41 µl/cm(2) and of percentage inhibition rate (PIR) of 77.3 %, respectively. Fumigation assay was comparatively more effective with LC(50) of 48.6 µl/L against housefly larvae, and a PIR value of 100 % against housefly pupae. The monoterpenes, citral, and 1,8-cineole, when assessed for their insecticidal activity against housefly larvae, showed LC(50) of 0.002 and 0.01 µl/cm(2) (contact toxicity assay) and LC(50) of 3.3 and 2.4 µl/L (fumigation assay). For pupicidal assay, both citral and 1,8-cineole had a PIR value of 100 %. High efficacy of citral and 1,8-cineole against housefly, established them to be an active insecticidal agent of C. citratus oil. The study demonstrates potentiality of C. citratus oil as an excellent insecticide for housefly control, and the results open up the opportunity of oil/monoterpenes being developed into an eco-friendly, economical, and acceptable product.

Interferon-gamma release assay has poor diagnostic accuracy in differentiating intestinal tuberculosis from Crohn's disease in tuberculosis endemic areas.

BACKGROUND/AIMS: Intestinal tuberculosis (ITB) and Crohn's disease (CD) frequently present with a diagnostic dilemma because of similar presentation. Interferon-gamma release assay (IGRA) has been used in differentiating ITB from CD, but with sparse reports on its diagnostic accuracy in tuberculosis endemic regions and this study evaluated the same. METHODS: Patients with definitive diagnosis of ITB (n=59) or CD (n=49) who underwent IGRA testing (n=307) were retrospectively included at All India Institute of Medical Sciences, New Delhi (July 2014 to September 2021). CD or ITB was diagnosed as per standard criteria. IGRA was considered positive at >0.35 IU/mL. Relevant data was collected and IGRA results were compared between ITB and CD to determine its accuracy. RESULTS: Among 59 ITB patients (mean age, 32.6±13.1 years; median disease duration, 1 year; male, 59.3%), 24 were positive and 35 tested negative for IGRA. Among 49 CD patients (mean age, 37.8±14.0; median disease duration, 4 years; male, 61.2%), 12 were positive and 37 tested negative for IGRA. Hence, for diagnosing ITB, IGRA showed a sensitivity, specificity, positive and negative predictive values of 40.68%, 75.51%, 66.67%, and 51.39%, respectively. The area under the curve of IGRA for ITB diagnosis was 0.66 (95% confidence interval, 0.55-0.75). In a subset (n=64), tuberculin skin test (TST) showed sensitivity, specificity, positive and negative predictive values of 64.7%, 73.3%, 73.3%, and 64.71%, respectively. IGRA and TST were concordant in 38 (59.4%) patients with κ=0.17. CONCLUSIONS: In a tuberculosis endemic region, IGRA had poor diagnostic accuracy for differentiating ITB from CD, suggesting a limited value of IGRA in this setting.