Publications by authors named "Aditi Kumar"

42 Publications

The impact of treatment with bile acid sequestrants on quality of life in patients with bile acid diarrhoea.

BMC Gastroenterol 2022 Jul 2;22(1):325. Epub 2022 Jul 2.

The Royal Wolverhampton NHS Trust, Wolverhampton Road, Wolverhampton, WV10 0QP, UK.

Background: Bile acid diarrhoea (BAD) can be severely debilitating and negatively affect patients' quality of life (QoL). We carried out a multi-centre prospective study exploring QoL outcomes in patients with BAD after treatment with colesevelam.

Methods: Patients with or without a positive 23-seleno-25-homotaurocholic acid (SeHCAT) scan were recruited and categorised into four groups: SeHCAT negative control group (CG), idiopathic BAD, post-cholecystectomy (PC) and post-terminal ileal resection for Crohn's disease (CD). Patients with a positive SeHCAT were treated with colesevelam and dosing was titrated to symptomatic response. Patients were reviewed at 4- and 8-weekly intervals and QoL was evaluated by EQ-5D-3L, SF-36, IBDQ-32 at each visit (where relevant). Patients with a negative SeHCAT (CG cohort) completed one set of questionnaires before being discharged from the study.

Results: 47 patients (BAD = 24, PC = 12, CD = 11) completed paired QoL questionnaires before and after treatment and 30 CG patients completed a baseline questionnaire. There was a significant improvement in IBDQ-32 mean scores before and after treatment in CD patients [134.6 (95%CI 112.5-156.6) and 158.4 (136.1-180.6), respectively (p = 0.007). Following treatment, BAD patients had significantly improved mean SF-36 scores in the "Role limitation due to physical health" dimension (p = 0.02) and in the overall mental component summary (p = 0.03). Prior to starting treatment, BAD patients had the lowest scores in the 'activity' dimension of the EQ-5D-3L (p = 0.04), which improved significantly after treatment (p = 0.002). Overall, the BAD and CD cohort showed improved mean scores with treatment in all components of the SF-36 and EQ-5D-3L, while the PC cohort showed a general decline in mean scores after treatment. 55% of patients clinically responded to treatment of which 41.7%, 58.3% and 81.8% responded from the BAD, PC and CD groups respectively. Correlations between those deemed as responders with improvements on the SF-36 and EQ-5D dimensions were not statistically significant.

Conclusion: Our results demonstrate improved QoL in the BAD and CD cohort with treatment. Further larger studies are recommended specifically investigating the PC cohort and whether patients may improve with newer treatments such as FXR agonists. Trial registration Ethical approval REC Ref: 16/LO/1325.
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http://dx.doi.org/10.1186/s12876-022-02404-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9250209PMC
July 2022

Variability in the Pre-Analytical Stages Influences Microbiome Laboratory Analyses.

Genes (Basel) 2022 Jun 15;13(6). Epub 2022 Jun 15.

Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton WV1 1LY, UK.

Introduction: There are numerous confounding variables in the pre-analytical steps in the analysis of gut microbial composition that affect data consistency and reproducibility. This study compared two DNA extraction methods from the same faecal samples to analyse differences in microbial composition.

Methods: DNA was extracted from 20 faecal samples using either (A) chemical/enzymatic heat lysis (lysis buffer, proteinase K, 95 °C + 70 °C) or (B) mechanical and chemical/enzymatic heat lysis (bead-beating, lysis buffer, proteinase K, 65 °C). Gut microbiota was mapped through the 16S rRNA gene (V3-V9) using a set of pre-selected DNA probes targeting >300 bacteria on different taxonomic levels. Apart from the pre-analytical DNA extraction technique, all other parameters including microbial analysis remained the same. Bacterial abundance and deviations in the microbiome were compared between the two methods.

Results: Significant variation in bacterial abundance was seen between the different DNA extraction techniques, with a higher yield of species noted in the combined mechanical and heat lysis technique (B). The five predominant bacteria seen in both (A) and (B) were spp. and spp. ( NS), followed by ( 0.005), ( 0.0001), spp. ( 0.0001) and ( 0.0001).

Conclusion: As microbial testing becomes more easily and commercially accessible, a unified international consensus for optimal sampling and DNA isolation procedures must be implemented for robustness and reproducibility of the results.
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http://dx.doi.org/10.3390/genes13061069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9223004PMC
June 2022

Gastroenterology 2022: Groundhog Day.

Frontline Gastroenterol 2022 19;13(4):349-351. Epub 2022 Feb 19.

Gastroenterology Department, Royal Wolverhampton Hospitals NHS Trust, Wolverhampton, UK.

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http://dx.doi.org/10.1136/flgastro-2022-102111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9186062PMC
February 2022

Twitter debate: controversies in pregnancy in IBD and liver disease.

Frontline Gastroenterol 2022 21;13(4):355-357. Epub 2021 Sep 21.

Gastroenterology, St James's University Hospital, Leeds, UK.

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http://dx.doi.org/10.1136/flgastro-2021-101998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9186033PMC
September 2021

A single faecal bile acid stool test demonstrates potential efficacy in replacing SeHCAT testing for bile acid diarrhoea in selected patients.

Sci Rep 2022 05 18;12(1):8313. Epub 2022 May 18.

Clinical Chemistry, Black Country Pathology Services, The Royal Wolverhampton NHS Trust, Wolverhampton, UK.

This study examines the validity of measuring faecal bile acids (FBA) in a single stool sample as a diagnostic tool for bile acid diarrhoea (BAD) by direct comparison to the selenium-homotaurocholic acid (SeHCAT) scan. A prospective observational study was undertaken. Patients with chronic diarrhoea (> 6 weeks) being investigated for potential BAD with SeHCAT scan provided stool samples for measurement of FBA, using an enzyme-linked immunosorbent assay. Patients were characterised into four groups: SeHCAT negative control group, post-cholecystectomy, idiopathic BAD and post-operative terminal ileal resected Crohn's disease. Stool samples were collected at baseline and 8-weeks post treatment to determine whether FBA measurement could be used to monitor therapeutic response. 113 patients had a stool sample to directly compare with their SeHCAT result. FBA concentrations (μmol/g) and interquartile ranges in patients in the control group (2.8; 1.6-4.2), BAD (3.6; 1.9-7.2) and post-cholecystectomy cohort 3.8 (2.3-6.8) were similar, but all were significantly lower (p < 0.001) compared to the Crohn's disease cohort (11.8; 10.1-16.2). FBA concentrations in patients with SeHCAT retention of < 15% (4.95; 2.6-10.5) and < 5% (9.9; 4.8-15.4) were significantly higher than those with a SeHCAT retention > 15% (2.6; 1.6-4.2); (p < 0.001 and p < 0.0001, respectively). The sensitivity and specificity using FBA cut-off of 1.6 μmol/g (using ≤ 15% SeHCAT retention as diagnostic of BAD) were 90% and 25% respectively. A single random stool sample may have potential use in diagnosing severe BAD or BAD in Crohn's patients. Larger studies are now needed to confirm the potential efficacy of this test to accurately diagnose BAD in the absence of SeHCAT testing.
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http://dx.doi.org/10.1038/s41598-022-12003-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9117305PMC
May 2022

Personalised medicine in IBD: don't dispose of the sledgehammer just yet.

Therap Adv Gastroenterol 2022 18;15:17562848221092562. Epub 2022 Apr 18.

Department of Gastroenterology, Northern Hospital, Epping, Victoria, Australia.

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http://dx.doi.org/10.1177/17562848221092562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9019394PMC
April 2022

Bile Acids and the Microbiome: Making Sense of This Dynamic Relationship in Their Role and Management in Crohn's Disease.

Can J Gastroenterol Hepatol 2022 22;2022:8416578. Epub 2022 Mar 22.

Department of Gastroenterology, The Royal Wolverhampton NHS Trust, New Cross Hospital, Wolverhampton, UK.

Background: Bile acids help maintain the physiological balance of the gut microbiome and the integrity of the intestinal epithelial barrier. Similarly, intestinal bacteria play a major role in bile acid metabolism as they are involved in crucial biotransformation steps in the enterohepatic circulation pathway. Understanding the relationship between bile acid signalling and the gut microbiome in Crohn's disease can help target new and innovative treatment strategies.

Aims: This review summarises the relationship between bile acids and the microbiome in Crohn's disease and discusses potential novel therapeutic options.

Methods: We performed a literature review on bile acid signalling, its effect on the gut microbiome, and therapeutic applications in Crohn's disease.

Results: Current research suggests that there is a strong interplay between the dysregulated microbiota, bile acid metabolism, and the mucosal immune system that can result in a changed immunological function, triggering the inflammatory response in Crohn's disease. Recent studies have demonstrated an association with altering the enterohepatic circulation and activating the farnesoid X receptor signalling pathway with the use of probiotics and faecal microbial transplantation, respectively. Bile acid sequestrants have been shown to have anti-inflammatory, cytoprotective, and anti-apoptotic properties with the potential to alter the intestinal microbial composition, suggesting a possible role in inducing and maintaining Crohn's disease.

Conclusions: Active Crohn's disease has been correlated with changes in bacterial concentrations, which may be associated with changes in bile acid modification. Further research should focus on targeting these areas for future therapeutic options.
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http://dx.doi.org/10.1155/2022/8416578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8964223PMC
April 2022

Insight from patients and healthcare professionals on the implementation of virtual clinics in patients with inflammatory bowel disease.

Frontline Gastroenterol 2022 25;13(2):104-110. Epub 2021 Feb 25.

Department of Gastroenterology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.

Introduction: During COVID-19, the management of outpatient inflammatory bowel disease (IBD) changed from face-to-face (F2F) to telephone and video consultations across the UK. We surveyed patients with IBD and IBD healthcare professionals (HCPs) to evaluate the impact of this abrupt transition on patient and HCP satisfaction outcomes, including the barriers and enablers of this service.

Methods: Patient satisfaction surveys were sent to patients who had a telephone consultation from May to July 2020. A second survey was sent to IBD HCPs across the UK. Questions from both surveys consisted of a mixture of multiple-choice options, ranking answers as well as short-answer questions.

Results: 210 patients and 114 HCPs completed the survey. During COVID-19, there was a significantly greater use of telephone, video or a mixture of consultation. F2F consultations were consistently preferred by patients, with 50% of patients indicating they did not want the option of for video consultations. Patients were more likely to prefer a telephone consultation if they were stable and needed routine review. Significantly fewer HCPs (5.3%) intend to use F2F consultations alone, preferring the use of telephone (20.2%) or combinations of telephone/F2F (22.8%), telephone/video (4.4%) or combination of all three consultation types (34.2%). 63% indicated they intend to incorporate video consultations in the future.

Conclusion: Telephone and video consultations need to be balanced proportionately with F2F clinics to achieve both patient and HCP satisfaction. Further research needs to be done to explore the use of video medicine in patients with IBD.
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http://dx.doi.org/10.1136/flgastro-2020-101714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8862460PMC
February 2021

A review of the therapeutic management of Crohn's disease.

Therap Adv Gastroenterol 2022 17;15:17562848221078456. Epub 2022 Feb 17.

Department of Gastroenterology, Northern Care Alliance NHS Foundation NHS Trust, Manchester, UK.

Crohn's disease is a chronic inflammatory, relapsing-remitting, and progressive gastrointestinal disorder with an often-negative impact on the physical, emotional, and psychological well-being. Over the past two decades, the medical compendium for the treatment of Crohn's disease has increased significantly, enabling treatment beyond symptoms. Indeed, early and timely use of effective medical therapy has been reflected by improved outcomes with reduction in surgery and ability to achieve clinical and endoscopic remission, reduce corticosteroid dependance, and prevent long-term complications in more patients. In this review, we discuss the key milestones in the medical management of Crohn's disease.
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http://dx.doi.org/10.1177/17562848221078456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8859667PMC
February 2022

Iron deficiency anaemia: pathophysiology, assessment, practical management.

BMJ Open Gastroenterol 2022 01;9(1)

Department of Gastroenterology, The Royal Wolverhampton NHS Trust, Wolverhampton, UK.

The WHO has recognised iron deficiency anaemia (IDA) as the most common nutritional deficiency in the world, with 30% of the population being affected with this condition. Although the most common causes of IDA are gastrointestinal bleeding and menstruation in women, decreased dietary iron and decreased iron absorption are also culpable causes. Patients with IDA should be treated with the aim of replenishing iron stores and returning the haemoglobin to a normal level. This has shown to improve quality of life, morbidity, prognosis in chronic disease and outcomes in pregnancy. Iron deficiency occurs in many chronic inflammatory conditions, including congestive cardiac failure, chronic kidney disease and inflammatory bowel disease. This article will provide an updated overview on diagnosis and management of IDA in patients with chronic conditions, preoperative and in pregnancy. We will discuss the benefits and limitations of oral versus intravenous iron replacement in each cohort, with an overview on cost analysis between the different iron formulations currently on the market.
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http://dx.doi.org/10.1136/bmjgast-2021-000759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8744124PMC
January 2022

Comparative Outcomes of Budesonide MMX versus Prednisolone for Ulcerative Colitis: Results from a British Retrospective Multi-Centre Real-World Study.

J Clin Med 2021 Sep 23;10(19). Epub 2021 Sep 23.

Leeds Gastroenterology Institute, Leeds Teaching Hospitals, Leeds LS9 7TF, UK.

During the COVID-19 pandemic many IBD units chose Budesonide MMX (Cortiment) as the first-line treatment for flares of ulcerative colitis (UC) in outpatients for its favourable side effect profile. This retrospective study of all UC patients treated with oral steroids between 1 March 2019-30 June 2019 and 1 March 2020-30 June 2020 aimed to compare Cortiment with Prednisolone in routine clinical practice. Outcomes included the need for hospitalisation for acute severe ulcerative colitis, symptoms at four weeks and end of treatment, and the need for rescue Prednisolone. The 2019 and 2020 cohorts did not differ at the baseline. Cortiment prescriptions rose from 24.5% in 2019 to 70.1% in 2020 ( < 0.001). At week four there were significant differences between 2019 and 2020 in mean bowel frequency (3.49 vs. 5.85, = 0.001), rectal bleeding <50% (89.7% vs. 73.1% of patients, = 0.039), and physician global assessment (PGA) (39.2% vs. 19.8% in remission, = 0.045). There was no significant difference in hospital admissions, rectal bleeding, and PGA at week eight. Rescue Prednisolone was required in 10% of Cortiment patients in 2019 vs. 31.3% in 2020 ( = 0.058). Active IBD is associated with worse COVID-19 outcomes prompting the careful evaluation of the choice of first-line steroid for UC, as Cortiment was associated with worse outcomes at four weeks.
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http://dx.doi.org/10.3390/jcm10194329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8509767PMC
September 2021

The UPTAKE study: a cross-sectional survey examining the insights and beliefs of the UK population on COVID-19 vaccine uptake and hesitancy.

BMJ Open 2021 06 15;11(6):e048856. Epub 2021 Jun 15.

Department of Gastroenterology and Haematology, Royal Wolverhampton Hospitals NHS Trust, Wolverhampton, UK.

Objective: A key challenge towards a successful COVID-19 vaccine uptake is vaccine hesitancy. We examine and provide novel insights on the key drivers and barriers towards COVID-19 vaccine uptake.

Design: This study involved an anonymous cross-sectional online survey circulated across the UK in September 2020. The survey was designed to include several sections to collect demographic data and responses on (1) extent of agreement regarding various statements about COVID-19 and vaccinations, (2) previous vaccination habits (eg, if they had previously declined vaccination) and (3) interest in participation in vaccine trials. Multinominal logistic models examined demographic factors that may impact vaccine uptake. We used principle component analysis and text mining to explore perception related to vaccine uptake.

Setting: The survey was circulated through various media, including posts on social media networks (Facebook, Twitter, LinkedIn and Instagram), national radio, news articles, Clinical Research Network website and newsletter, and through 150 West Midlands general practices via a text messaging service.

Participants: There were a total of 4884 respondents of which 9.44% were black, Asian and minority ethnic (BAME) group. The majority were women (n=3416, 69.9%) and of white ethnicity (n=4127, 84.5%).

Results: Regarding respondents, overall, 3873 (79.3%) were interested in taking approved COVID-19 vaccines, while 677 (13.9%) were unsure, and 334 (6.8%) would not take a vaccine. Participants aged over 70 years old (OR=4.63) and the BAME community (OR=5.48) were more likely to take an approved vaccine. Smokers (OR=0.45) and respondents with no known illness (OR=0.70) were less likely to accept approved vaccines. The study identified 16 key reasons for not accepting approved vaccines, the most common (60%) being the possibility of the COVID-19 vaccine having side effects.

Conclusions: This study provides an insight into focusing on specific populations to reduce vaccine hesitancy. This proves crucial in managing the COVID-19 pandemic.
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http://dx.doi.org/10.1136/bmjopen-2021-048856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210694PMC
June 2021

Differences in the On- and Off-Tumor Microbiota between Right- and Left-Sided Colorectal Cancer.

Microorganisms 2021 May 20;9(5). Epub 2021 May 20.

Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton WV1 1LY, UK.

This study aims to determine differences in the on- and off-tumor microbiota between patients with right- and left-sided colorectal cancer. Microbiome profiling of tumor and tumor-adjacent biopsies from patients with right-sided ( = 17) and left-sided ( = 7) colorectal adenocarcinoma was performed using 16S ribosomal RNA sequencing. Off-tumor alpha and beta diversity were significantly different between right- and left-sided colorectal cancer patients. However, no differences in on-tumor diversity were observed between tumor locations. Comparing the off-tumor microbiota showed the right colon to be enriched with species of the Lachnoclostridium, Selenomonas, and Ruminococcus genera. Whereas the left colon is enriched with Epsilonbacteraeota phylum, Campylobacteria class, and Pasteurellales and Campylobacterales orders, in contrast, the on-tumor microbiota showed relatively fewer differences in bacterial taxonomy between tumor sites, with left tumors being enriched with Methylophilaceae and Vadin BE97 families and Alloprevotella, Intestinibacter, Romboutsia, and Ruminococcus 2 genera. Patients with left-sided colorectal cancer had large taxonomic differences between their paired on- and off-tumor microbiota, while patients with right-sided colorectal cancer showed relatively fewer taxonomic differences. Collectively, this suggests that the right and left colon show distinctive bacterial populations; however, the presence of a colonic tumor leads to a more consistent microbiota between locations.
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http://dx.doi.org/10.3390/microorganisms9051108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160982PMC
May 2021

Correlating Charge-Transfer State Lifetimes with Material Energetics in Polymer:Non-Fullerene Acceptor Organic Solar Cells.

J Am Chem Soc 2021 May 23;143(20):7599-7603. Epub 2021 Apr 23.

Department of Chemistry and Centre for Processable Electronics, Imperial College London, London, W12 0BZ, United Kingdom.

Minimizing the energy offset between the lowest exciton and charge-transfer (CT) states is a widely employed strategy to suppress the energy loss () in polymer:non-fullerene acceptor (NFA) organic solar cells (OSCs). In this work, transient absorption spectroscopy is employed to determine CT state lifetimes in a series of low energy loss polymer:NFA blends. The CT state lifetime is observed to show an inverse energy gap law dependence and decreases as the energy loss is reduced. This behavior is assigned to increased mixing/hybridization between these CT states and shorter-lived singlet excitons of the lower gap component as the energy offset Δ is reduced. This study highlights how achieving longer exciton and CT state lifetimes has the potential for further enhancement of OSC efficiencies.
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http://dx.doi.org/10.1021/jacs.1c00584DOI Listing
May 2021

The UPTAKE study: implications for the future of COVID-19 vaccination trial recruitment in UK and beyond.

Trials 2021 Apr 20;22(1):296. Epub 2021 Apr 20.

The Royal Wolverhampton NHS Trust, New Cross Hospital, Wolverhampton Road, Wolverhampton, West Midlands, WV10 0QP, UK.

Background: Developing a safe and effective vaccine will be the principal way of controlling the COVID-19 pandemic. However, current COVID-19 vaccination trials are not adequately representing a diverse participant population in terms of age, ethnicity and comorbidities. Achieving the representative recruitment targets that are adequately powered to the study remains one of the greatest challenges in clinical trial management. To ensure accuracy and generalisability of the safety and efficacy conclusions generated by clinical trials, it is crucial to recruit patient cohorts as representative as possible of the future target population. Missing these targets can lead to reduced validity of the study results and can often slow down drug development leading to costly delays.

Objective: This study explores the key factors related to perceptions and participation in vaccination trials.

Methods: This study involved an anonymous cross-sectional online survey circulated across the UK. Statistical analysis was done in six phases. Multi-nominal logistic models examined demographic and geographic factors that may impact vaccine uptake.

Results: The survey had 4884 participants of which 9.44% were Black Asian Minority Ethnic (BAME). Overall, 2020 (41.4%) respondents were interested in participating in vaccine trials; 27.6% of the respondents were not interested and 31.1% were unsure. The most interested groups were male (OR = 1.29), graduates (OR = 1.28), the 40-49 and 50-59 age groups (OR = 1.88 and OR = 1.46 respectively) and those with no health issues (OR = 1.06). The least interested groups were BAME (OR = 0.43), those from villages and small towns (OR = 0.66 and 0.54 respectively) and those aged 70 and above (OR = 1.11).

Conclusions: In order to have a vaccination that is generalisable to the entire population, greater work needs to be done in engaging a diverse cohort of participants. Public health campaigns need to be targeted in improving trial recruitment rates for the elderly, BAME community and the less educated rural population.
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http://dx.doi.org/10.1186/s13063-021-05250-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057665PMC
April 2021

Liver Abscess in Children-experience From a Single Tertiary Care Center of North India: Etiology, Clinical Profile and Predictors of Complications.

Pediatr Infect Dis J 2021 05;40(5):e179-e184

Department of Medical Parasitology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Background: Liver abscess (LA), a common problem in children in the tropics, is believed to be mostly pyogenic (PLA), sometimes amebic (ALA). We aimed to analyze the clinical profile, etiology, risk factors for complications, management and outcomes of LA in children.

Methods: The details of 81 children with LA managed in a tertiary set up over a period of 3 years were analyzed. A comparison of different parameters was performed with respect to etiology and complications.

Results: ALA, PLA and mixed infection LA were diagnosed in 40 (49.4%), 32 (39.5%) and 9 (11.1%) children. The triad of fever, hepatomegaly and right upper quadrant tenderness was seen in 65 (80.2%). Coagulopathy was observed in 60 (77%) and jaundice in 12 (14.8%). Majority (71.6%) had a single LA in the right lobe (69%). Conservative, percutaneous needle aspiration, percutaneous catheter drainage and surgical drainage were done in 11.1%, 3.7%, 82.7% and 2.5%, respectively. Forty-three (53.1%) had complicated LA with rupture in 55.8% and vascular thrombosis in 16.2%. Children with complicated LA had higher alanine transaminase, prolonged prothrombin time/international normalized ratio, low serum protein and albumin levels (P < 0.05). Median duration of follow-up was 2 months and mean time to resolution of LA was 48.5 ± 18 days.

Conclusions: ALA is the commonest cause of pediatric LA in endemic regions and is difficult to differentiate from PLA clinically. Percutaneous catheter drainage is safe and effective modality for the management of LA in children. A higher alanine transaminase, prolonged prothrombin time/international normalized ratio and low serum albumin levels (<3 g/dL) at presentation identify complicated LA.
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http://dx.doi.org/10.1097/INF.0000000000003053DOI Listing
May 2021

Oral and Intravenous Iron Therapy Differentially Alter the On- and Off-Tumor Microbiota in Anemic Colorectal Cancer Patients.

Cancers (Basel) 2021 Mar 16;13(6). Epub 2021 Mar 16.

Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton WV1 1LY, UK.

Iron deficiency anemia is a common complication of colorectal cancer and may require iron therapy. Oral iron can increase the iron available to gut bacteria and may alter the colonic microbiota. We performed an intervention study to compare oral and intravenous iron therapy on the colonic tumor-associated (on-tumor) and paired non-tumor-associated adjacent (off-tumor) microbiota. Anemic patients with colorectal adenocarcinoma received either oral ferrous sulphate ( = 16) or intravenous ferric carboxymaltose ( = 24). On- and off-tumor biopsies were obtained post-surgery and microbial profiling was performed using 16S ribosomal RNA analysis. Off-tumor α- and β-diversity were significantly different between iron treatment groups. No differences in on-tumor diversity were observed. Off-tumor microbiota of oral iron-treated patients showed higher abundances of the orders Clostridiales, Cytophagales, and Anaeroplasmatales compared to intravenous iron-treated patients. The on-tumor microbiota was enriched with the orders Lactobacillales and Alteromonadales in the oral and intravenous iron groups, respectively. The on- and off-tumor microbiota associated with intravenous iron-treated patients infers increased abundances of enzymes involved in iron sequestration and anti-inflammatory/oncogenic metabolite production, compared to oral iron-treated patients. Collectively, this suggests that intravenous iron may be a more appropriate therapy to limit adverse microbial outcomes compared to oral iron.
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http://dx.doi.org/10.3390/cancers13061341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002270PMC
March 2021

The impact of SARS-CoV-2 variants on IBD management.

Lancet Gastroenterol Hepatol 2021 05 10;6(5):343-344. Epub 2021 Mar 10.

Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, UK; Department of Gastroenterology, Royal Wolverhampton NHS Trust, Wolverhampton, UK.

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http://dx.doi.org/10.1016/S2468-1253(21)00075-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943390PMC
May 2021

Bilateral renal cortical necrosis in a child with acute pancreatitis.

Saudi J Kidney Dis Transpl 2020 Nov-Dec;31(6):1395-1398

Division of Pediatric Gastroenterology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Bilateral renal cortical necrosis (RCN) as a cause of acute kidney injury is very rare in the pediatric population. Progression to end-stage renal disease is seen virtually in every patient with RCN. There are many causes for the occurrence of cortical necrosis in children, with severe pancreatitis being a rarity. In this report, we describe a child with severe acute pancreatitis complicated by bilateral RCN.
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http://dx.doi.org/10.4103/1319-2442.308353DOI Listing
October 2021

Iron Therapy in Inflammatory Bowel Disease.

Nutrients 2020 Nov 12;12(11). Epub 2020 Nov 12.

The Royal Wolverhampton NHS Trust, Wolverhampton WV10 0QP, UK.

The most common complication seen in inflammatory bowel disease (IBD) patients is iron deficiency anaemia (IDA). Symptoms such as chronic fatigue can be as debilitating to IBD patients as pathological symptoms of abdominal pain and diarrhoea. Recognising and correcting anaemia may be as important as managing IBD symptoms and improving overall quality of life. Thus, iron replacement should be commenced the moment IDA is identified. Although intravenous iron is now considered standard treatment for IBD patients in Europe, oral iron still appears to be the preferred option. Advantages of oral iron include greater availability, lower costs and ease of applicability. However, its multitude of side effects, impact on the microbiome and further exacerbating IBD activity can have consequences on patient compliance. The newer oral iron formulations show promising safety and efficacy data with a good side effect profile. Intravenous iron formulations bypass the gastrointestinal tract absorption thereby leading to less side effects. Multiple studies have shown its superiority compared to oral formulations although its risk for hypersensitivity reactions continue to lead to clinician hesitancy in prescribing this formulation. This article provides an updated review on diagnosis and management of IDA in IBD patients, discussing the newer oral and intravenous formulations.
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http://dx.doi.org/10.3390/nu12113478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697745PMC
November 2020

Reply to comment on 'Preoperative intravenous iron therapy and survival after colorectal cancer surgery: long term results from the IVICA randomized controlled trial'.

Colorectal Dis 2021 01 10;23(1):323-324. Epub 2020 Nov 10.

National Institute for Health Research Biomedical Research Unit, Gastrointestinal and Liver Diseases, Nottingham University Hospitals NHS Trust, Nottingham, UK.

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http://dx.doi.org/10.1111/codi.15414DOI Listing
January 2021

COVID-19 vaccinations in patients with inflammatory bowel disease.

Lancet Gastroenterol Hepatol 2020 11 21;5(11):965-966. Epub 2020 Sep 21.

Royal Wolverhampton Trust, New Cross Hospital, Wolverhampton WV10 0QP, UK; Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, UK.

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http://dx.doi.org/10.1016/S2468-1253(20)30295-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505629PMC
November 2020

Influence of Iron on the Gut Microbiota in Colorectal Cancer.

Nutrients 2020 Aug 20;12(9). Epub 2020 Aug 20.

Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton WV1 1LY, UK.

Perturbations of the colonic microbiota can contribute to the initiation and progression of colorectal cancer, leading to an increase in pathogenic bacteria at the expense of protective bacteria. This can contribute to disease through increasing carcinogenic metabolite/toxin production, inducing inflammation, and activating oncogenic signaling. To limit disease progression, external factors that may influence the colonic microbiota need to be considered in patients with colorectal cancer. One major factor that can influence the colonic microbiota is iron. Iron is an essential micronutrient that is required by both prokaryotes and eukaryotes for cellular function. Most pathogenic bacteria have heightened iron acquisition mechanisms and therefore tend to outcompete protective bacteria for free iron. Colorectal cancer patients often present with anemia due to iron deficiency, and thus they require iron therapy. Depending upon the route of administration, iron therapy has the potential to contribute to a procarciongenic microbiota. Orally administered iron is the common treatment for anemia in these patients but can lead to an increased gut iron concentration. This suggests the need to reassess the route of iron therapy in these patients. Currently, this has only been assessed in murine studies, with human trials being necessary to unravel the potential microbial outcomes of iron therapy.
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http://dx.doi.org/10.3390/nu12092512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551435PMC
August 2020

Small Molecule Inhibitors Targeting Gα2 Protein Attenuate Migration of Cancer Cells.

Cancers (Basel) 2020 Jun 19;12(6). Epub 2020 Jun 19.

Center for Cancer Research and Therapeutic Development, Clark Atlanta University, Atlanta, GA 30314, USA.

Heterotrimeric G-proteins are ubiquitously expressed in several cancers, and they transduce signals from activated G-protein coupled receptors. These proteins have numerous biological functions, and they are becoming interesting target molecules in cancer therapy. Previously, we have shown that heterotrimeric G-protein subunit alphai2 (Gα2) has an essential role in the migration and invasion of prostate cancer cells. Using a structure-based approach, we have synthesized optimized small molecule inhibitors that are able to prevent specifically the activation of the Gα2 subunit, keeping the protein in its inactive GDP-bound state. We observed that two of the compounds ( and ) at 10 μΜ significantly inhibited the migratory behavior of the PC3 and DU145 prostate cancer cell lines. Additionally, compound at 10 μΜ blocked the activation of Gα2 in oxytocin-stimulated prostate cancer PC3 cells, and inhibited the migratory capability of DU145 cells overexpressing the constitutively active form of Gα2, under basal and EGF-stimulated conditions. We also observed that the knockdown or inhibition of Gα2 negatively regulated migration of renal and ovarian cancer cell lines. Our results suggest that small molecule inhibitors of Gα2 have potential as leads for discovering novel anti-metastatic agents for attenuating the capability of cancer cells to spread and invade to distant sites.
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http://dx.doi.org/10.3390/cancers12061631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353059PMC
June 2020

COVID-19 Diagnostics, Tools, and Prevention.

Diagnostics (Basel) 2020 Jun 16;10(6). Epub 2020 Jun 16.

Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA.

The Coronavirus Disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), outbreak from Wuhan City, Hubei province, China in 2019 has become an ongoing global health emergency. The emerging virus, SARS-CoV-2, causes coughing, fever, muscle ache, and shortness of breath or dyspnea in symptomatic patients. The pathogenic particles that are generated by coughing and sneezing remain suspended in the air or attach to a surface to facilitate transmission in an aerosol form. This review focuses on the recent trends in pandemic biology, diagnostics methods, prevention tools, and policies for COVID-19 management. To meet the growing demand for medical supplies during the COVID-19 era, a variety of personal protective equipment (PPE) and ventilators have been developed using do-it-yourself (DIY) manufacturing. COVID-19 diagnosis and the prediction of virus transmission are analyzed by machine learning algorithms, simulations, and digital monitoring. Until the discovery of a clinically approved vaccine for COVID-19, pandemics remain a public concern. Therefore, technological developments, biomedical research, and policy development are needed to decipher the coronavirus mechanism and epidemiological characteristics, prevent transmission, and develop therapeutic drugs.
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http://dx.doi.org/10.3390/diagnostics10060409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344926PMC
June 2020

An International Phase 2 Study of Pazopanib in Progressive and Metastatic Thyroglobulin Antibody Negative Radioactive Iodine Refractory Differentiated Thyroid Cancer.

Thyroid 2020 09 29;30(9):1254-1262. Epub 2020 Jul 29.

Division of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester, Minnesota, USA.

Multikinase inhibitors have clinical activity in radioactive iodine refractory (RAIR) differentiated thyroid cancers (DTCs) but are not curative; optimal management and salvage therapies remain unclear. This study assessed clinical effects of pazopanib therapy in RAIR-DTC patients with progressive disease, examining in parallel biomarker that might forecast/precede therapeutic response. Assessment of responses and toxicities and of any association between thyroglobulin (Tg) changes cycle 1 and RECIST (response evaluation criteria in solid tumors) response to pazopanib therapy were prospectively undertaken in Tg antibody negative RAIR-DTC patients. RECIST progressive metastatic disease <6 months preceding enrollment was required. With a sample size of 68 (assuming 23 attaining partial response [PR]), there would be 90% chance of detecting a difference of >30% when the proportion of patients attaining PR whose Tg values decrease by >50% is >50% cycle 1 (one-sided  = 0.10, two sample test of proportions). Mean corpuscular volume (MCV) change or mutational status or pretreatment were also explored as early correlates of eventual RECIST response. From 2009 to 2011, 60 individuals were treated and evaluated; (one additional patient withdrew; another was found ineligible before therapy initiation); 91.7% had previous systemic therapy beyond RAI. Adverse events included one death (thromboembolic) deemed possibly pazopanib associated. Twenty-two confirmed RECIST PRs resulted (36.7%, confidence interval; CI [24.6-50.1]); mean administered 4-week cycles was 10. Among 44 fully accessible patients, the Tg nadir was greater among the 20 attaining PR (median: -86.8%; interquartile range [IQR]: -90.7% to -70.9%) compared with the 28 who did not (median: -69.0%; IQR: -78.1% to -27.7%, Wilcoxon rank-sum test:  = 0.002). However, the difference in the proportion of PRs among those whose Tg fell ≥50% after cycle 1 versus those that did not were not significantly correlated (-23.5% [CI: -55.3 to 8.3]; Fisher's exact test -value = 0.27). RECIST response was also not correlated with/predicted by early MCV change, receipt of prior therapy, or tumor mutational status. This trial prospectively confirmed pazopanib to have clinical activity and manageable toxicities in patients with progressive RAIR-DTC. Response to pazopanib, however, was not robustly forecast by early associated changes in Tg or MCV, by prior therapy, or by tumor mutational status. ClinicalTrials.gov NCT00625846.
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http://dx.doi.org/10.1089/thy.2019.0269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7482116PMC
September 2020

Role of noninvasive tools for prediction of clinically evident portal hypertension in children.

Eur J Gastroenterol Hepatol 2020 08;32(8):931-937

Department of Pathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Background: Noninvasive tools (NITs) for predicting varices in children with portal hypertension (PHTN) are infrequently used.

Methods: Eighty-five consecutive, treatment-naïve children with PHTN and 97 controls were enrolled study from July 2017 to November 2018. Each case was evaluated by esophagogastroduodenoscopy (EGD) and various NITs: platelet spleen size Z (PSZ), clinical prediction rule (CPR), King's variceal prediction rule (KVaPS), Splenic stiffness (SSM) and liver stiffness measurement (LSM) by point shear wave elastrography (pSWE).

Results: Had PHTN due to extra hepatic portal vein obstruction (EHPVO) and 70% due to cirrhosis [chronic liver disease (CLD)]. Sixty-five percent of PHTN cases had varices. Children with varices had lower platelet counts, lower albumin and larger spleens. SSM and LSM were significantly higher in cases as compared with controls. SSM was significantly higher in cases with varices than those without. SSM and LSM, at cutoffs of 3.8 and 3.2 kPa, respectively, discriminated PHTN cases from controls with an area under the curve (AUROC) of 0.67 (0.59-0.74). Both SSM and LSM predicted varices in CLD, but in EHPVO, only SSM predicted varices. SSM of 5.2 and 12.8 kPa, in CLD and EHPVO subgroups, respectively, had AUROC of 0.73 and 0.94 for variceal prediction. Blood-based NITs performed better in the CLD subgroup: aspartate aminotransferase platelet ratio index, CPR and KVPS predicted severity of PHTN with AUROC of 0.81, 0.92 and 0.93, respectively.

Conclusions: Blood-based NITs outperform elastography for prediction of PHTN/varices in children with CLD. SSM by pSWE is a better predictor of varices than LSM, especially in the EHPVO subgroup.
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http://dx.doi.org/10.1097/MEG.0000000000001716DOI Listing
August 2020

Capillary-Based and Stokes-Based Trapping of Serial Sections for Scalable 3D-EM Connectomics.

eNeuro 2020 Mar/Apr;7(2). Epub 2020 Apr 21.

Georgia Institute of Technology, G. W. Woodruff School of Mechanical Engineering, Atlanta, GA 30332.

Serial section electron microscopy (ssEM), a technique where volumes of tissue can be anatomically reconstructed by imaging consecutive tissue slices, has proven to be a powerful tool for the investigation of brain anatomy. Between the process of cutting the slices, or "sections," and imaging them, however, handling 10°-10 delicate sections remains a bottleneck in ssEM, especially for batches in the "mesoscale" regime, i.e., 10-10 sections. We present a tissue section handling device that transports and positions sections, accurately and repeatability, for automated, robotic section pick-up and placement onto an imaging substrate. The device interfaces with a conventional ultramicrotomy diamond knife, accomplishing in-line, exact-constraint trapping of sections with 100-μm repeatability. An associated mathematical model includes capillary-based and Stokes-based forces, accurately describing observed behavior and fundamentally extends the modeling of water-air interface forces. Using the device, we demonstrate and describe the limits of reliable handling of hundreds of slices onto a variety of electron and light microscopy substrates without significant defects ( = 8 datasets composed of 126 serial sections in an automated fashion with an average loss rate and throughput of 0.50% and 63 s/section, respectively. In total, this work represents an automated mesoscale serial sectioning system for scalable 3D-EM connectomics.
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http://dx.doi.org/10.1523/ENEURO.0328-19.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7174874PMC
June 2021

An interesting cause of chronic abdominal pain in a child.

Trop Doct 2020 Jan 17;50(1):63-64. Epub 2019 Sep 17.

Professor and Head, Division of Paediatric Gastroenterology, PGIMER, Chandigarh, India.

We encountered an eight-year-old boy who was subsequently diagnosed with a retroperitoneal ganglioneuroma. In view of the rarity of this tumour and its presentation, we are prompted to report this case.
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http://dx.doi.org/10.1177/0049475519876422DOI Listing
January 2020

Large-scale neuroanatomy using LASSO: Loop-based Automated Serial Sectioning Operation.

PLoS One 2018 23;13(10):e0206172. Epub 2018 Oct 23.

Allen Institute for Brain Science, Seattle, WA, United States of America.

Serial section transmission electron microscopy (ssTEM) is the most promising tool for investigating the three-dimensional anatomy of the brain with nanometer resolution. Yet as the field progresses to larger volumes of brain tissue, new methods for high-yield, low-cost, and high-throughput serial sectioning are required. Here, we introduce LASSO (Loop-based Automated Serial Sectioning Operation), in which serial sections are processed in "batches." Batches are quantized groups of individual sections that, in LASSO, are cut with a diamond knife, picked up from an attached waterboat, and placed onto microfabricated TEM substrates using rapid, accurate, and repeatable robotic tools. Additionally, we introduce mathematical models for ssTEM with respect to yield, throughput, and cost to access ssTEM scalability. To validate the method experimentally, we processed 729 serial sections of human brain tissue (~40 nm x 1 mm x 1 mm). Section yield was 727/729 (99.7%). Sections were placed accurately and repeatably (x-direction: -20 ± 110 μm (1 s.d.), y-direction: 60 ± 150 μm (1 s.d.)) with a mean cycle time of 43 s ± 12 s (1 s.d.). High-magnification (2.5 nm/px) TEM imaging was conducted to measure the image quality. We report no significant distortion, information loss, or substrate-derived artifacts in the TEM images. Quantitatively, the edge spread function across vesicle edges and image contrast were comparable, suggesting that LASSO does not negatively affect image quality. In total, LASSO compares favorably with traditional serial sectioning methods with respect to throughput, yield, and cost for large-scale experiments, and represents a flexible, scalable, and accessible technology platform to enable the next generation of neuroanatomical studies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0206172PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198950PMC
April 2019
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