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Summary: Background: Primary sclerosing cholangitis (PSC) is one of the leading indications for liver transplantation in Europe, and a major risk factor for cancer in inflammatory bowel disease (IBD). However, it is not known how the epidemiology of PSC will change as that of IBD evolves. The aim of this study is to provide nationwide statistics on the past and current prevalence of PSC and IBD across England, and forecast how this is likely to change over time. Methods: We accessed and analysed a nationwide population-based administrative healthcare registry, which houses prospectively accrued data since April 1st 2001. In so doing, the past and current prevalence of PSC-IBD and IBD alone was determined among 18–60-year-olds in England, alongside average annual percentage change rates (AAPC), between the 1st of January 2015 and 2020. Past and current prevalence data, alongside trends in incidence and event-free survival rates, were then used to forecast future prevalence between 2021 and 2027. Findings: In 2015, the prevalence of PSC with prior IBD diagnosis was 5.0 per 100,000 population, rising to 5.7 when including those with IBD diagnosed after PSC. In 2020, prevalence increased to 7.6 (8.6 accounting for IBD developing after PSC), yielding an AAPC of 8.8. In 2027, PSC-IBD prevalence is forecast to be 11.7 (95% prediction interval [PI]: 10.8–12.7), and 13.3 when accounting for IBD developing after PSC (AAPC: 6.4; 95% PI: 5.3–7.5). Comparatively, the prevalence of IBD alone rose among 18–60-year-olds from 384.3 in 2015 to 538.7 in 2020 (AAPC 7.0), and forecast to increase to 742.5 by 2027 (95% PI: 736.4–748.0; AAPC: 4.7, 95% PI: 4.6–4.8). Interpretation: The rate of growth in PSC-IBD is predicted to exceed IBD-alone. Further research is needed to understand changes in disease epidemiology, including aetiological drivers of developing (invariably progressive) liver disease in IBD, and the implications of rising case burden on health care resources. Funding: This study was supported by an unrestricted grant provided by Gilead Sciences.

Background Ulcerative colitis is an autoimmune reaction to imbalanced colonic microbiome in genetically predisposed patients. There have been four published randomised controlled trials of faecal microbiota transplant versus placebo in ulcerative colitis; three being positive. However, the methodology used varied and mechanistic data were sparse. Objective To identify an optimal faecal microbiota transplant delivery route to test in a future efficacy-powered randomised controlled trial. Design Prospective, multicentre, open-label, parallel-group, randomised pilot study. Participants were randomised in a 1 : 1 ratio to faecal microbiota transplant by nasogastric or by colonoscopy, minimised by partial Mayo score and current smoking status. Setting Three secondary care hospitals in the United Kingdom. Participants Thirty adult patients with mild to moderately active ulcerative colitis (partial Mayo score of ≥4 and ≤8). Interventions Faecal microbiota transplant samples were prepared at the University of Birmingham Microbiome Treatment Centre and administered to participants either via a nasogastric tube on 4 consecutive days repeated after a month (nasogastric) or by colonoscopy followed by 7 weekly enemas (COLON). Each treatment course was from a single matched donor. Participants and researchers underwent qualitative interviews regarding the faecal microbiota transplant experience. Main outcome measure Composite assessment of qualitative and quantitative data based on efficacy, acceptability and safety. Clinical response (primary measure of efficacy) was defined as a ≥3 point and ≥30% reduction in full Mayo score from randomisation to week 8 and a ≥1 point reduction in rectal bleeding subscore or absolute rectal bleeding subscore of 0 or 1. Results Thirty ulcerative colitis patients were randomised: 16 to nasogastric; 14 to COLON. Seven participants in the nasogastric arm and two in the COLON arm withdrew from treatment and clinical follow-up. Eight of 16 (50%) nasogastric participants were adherent compared to 12/14 (86%) COLON participants. Clinical response data were available for 20 of 30 randomised participants. Clinical response was seen in 2/8 (25%) nasogastric participants versus 9/12 (75%) COLON participants: adjusted risk ratio 2.94 (95% CI 0.84 to 10.30). Adverse events were reported in 11/16 (69%) nasogastric participants versus 11/14 (79%) COLON participants. There were three serious adverse events in two nasogastric participants. Faecal microbiota transplant was deemed an acceptable treatment for ulcerative colitis, with greater participant and clinician acceptability for the COLON route. Faecal microbiota transplant responders had a greater reduction in faecal calprotectin compared to non-responders (t-test p = 0.03) and increase in faecal microbiome diversity (Shannon diversity p < 0.01). In the whole cohort, a negative association between faecal calprotectin and diversity was seen (Kendall’s tau z = −2.8231, p = 0.004757). There were increases in faecal acetate (p = 0.05) and butyrate (p = 0.03) after faecal microbiota transplant intervention, but these were not associated with clinical response. A limitation was that this was an open-label pilot study, which was not powered to assess for efficacy of faecal microbiota transplant. Conclusions Faecal microbiota transplant delivered by the colonic route was considered safe and better tolerated than the nasogastric route. The colonic route was preferred by both participants and clinicians. Mechanistic signals indicated reduction in colonic inflammation and increased microbiome diversity in faecal microbiota transplant responders. Future work An efficacy-powered randomised controlled trial. Trial registration This trial is registered as ISRCTN74072945 and EudraCT 2015-005753-12. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 13/179/01) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 14. See the NIHR Funding and Awards website for further award information. Plain language summary Ulcerative colitis, a chronic inflammatory condition affecting the colon, results from the body’s immune response to imbalance in colonic microbes (microbiota). Faecal microbiota transplantation involves transferring processed donated stool samples from carefully screened healthy donors to ulcerative colitis patients aiming to correct the imbalance and reduce inflammation. There have been four trials comparing faecal microbiota transplant with placebo (dummy no treatment) to treat ulcerative colitis, and one which investigated faecal microbiota transplant with dietary intervention. Three of these studies showed encouraging benefit for faecal microbiota transplant. However, these studies varied in the methods used, with faecal microbiota transplant delivered either to the stomach or colon, or both. The aim of this study was to identify the best route of faecal microbiota transplant administration before undertaking a large-scale trial comparing faecal microbiota transplant with placebo. Between March 2018 and 30 April 2019 ulcerative colitis patients from three hospitals were randomly allocated to receive faecal microbiota transplant via either a tube inserted through the nose into the stomach on 4 consecutive days repeated after a month (nasogastric group; 16 participants) or by colonoscopy followed by 7 weekly enemas (COLON group; 14 participants). Faecal microbiota transplant was well accepted, with both patients with ulcerative colitis and healthcare staff stating a preference for the colonic route. Only 8 of 16 in the nasogastric group completed the study compared to 12 of 14 in the COLON group. Altogether, 9/12 (75%) in the COLON group improved compared with 2/8 (25%) in the nasogastric group. The majority of participants [11/14 (79%) COLON vs. 11/16 (69%) nasogastric] had mild, short-lived side effects following faecal microbiota transplant. There were three serious adverse events. Faecal calprotectin (indicating colonic inflammation) fell in responders and stool samples showed an increase in the number of microbial species after faecal microbiota transplant. At the end of the study, a recommendation was made by the Independent Oversight Committee to proceed to a large placebo-controlled randomised trial using the colonic route. Scientific summary Background Ulcerative colitis (UC) results from an exaggerated immune response to an imbalanced (dysbiotic) colonic microbiome in genetically predisposed patients. At the inception of this study, there had been four published randomised controlled trials (RCTs) comparing faecal microbiota transplantation (FMT) with placebo to treat UC in adults. Of these four seminal studies, three involved delivery of FMT via the colonic route and one a combination of delivery to the foregut and colon. This latter study was the only one of the four not to show a difference in efficacy compared to placebo. Foregut-delivered FMT is extensively and successfully used in clinical practice to treat Clostridioides difficile infection (CDI). From the results of the UC trials, FMT appeared to have therapeutic potential for UC. However, the methodology employed in these studies was varied and, taking into account the efficacy of FMT delivered to the foregut to treat CDI, there was uncertainty regarding the best route of delivery in the context of UC. Objectives The aims of this pilot study were as follows: to determine which FMT administration route [nasogastric (NG) or colonic (COLON)] should be investigated in a randomised double-blind, placebo-controlled trial to determine whether a full-scale RCT was feasible. In order to achieve these aims, the pilot study had the following clinical objectives. To assess the following: whether FMT by the NG route induces clinical response in patients with active UC whether FMT by the COLON route induces clinical response in patients with active UC tolerability and safety which route of FMT delivery (if any) was suitable to investigate in a full-scale RCT. The aims of the qualitative research were to assess the following: patient and clinician acceptability of FMT (NG route) patient and clinician acceptability of FMT (COLON route). The aims of the nested-mechanistic substudy were to assess the following: whether FMT by either route is associated with a change in faecal calprotectin as a surrogate marker of colonic inflammation changes in the colonic microbiome induced by FMT via each route changes in the metabolome [short-chain fatty acids (SCFAs)] induced by FMT via each route effect of diet (donors) time from stool donation to treatment. Methods In this prospective, multicentre, open-label, parallel group, randomised pilot study, adult patients with mild to moderate active UC (partial Mayo score of ≥4 and ≤8) were recruited from three centres in the UK (Birmingham, Glasgow and St Mark’s, London). Patients were randomised to receive FMT delivered either via a NG tube for delivery to the stomach (foregut-NG) on 4 consecutive days repeated after a month or by a combination of delivery through a colonoscope followed by 7 weekly enemas (hindgut-COLON). All participants underwent a treatment schedule using FMT derived, in each case, from a single donor. The primary outcome was a composite assessment of both qualitative and quantitative data based on efficacy, acceptability and safety. Clinical response (primary measure of efficacy) was defined as a ≥3 point and a ≥30% reduction in full Mayo score from randomisation to week 8 and a ≥1 point reduction in the rectal bleeding subscore or an absolute rectal bleeding subscore of 0 or 1. Patient and clinician acceptability of FMT and preference of treatment route was assessed through semi-structured qualitative research interviews. Interviews also explored reasons for adherence to treatment allocation and patients’ perspectives on FMT and trial experience. Participants were interviewed face to face or by telephone at two time points, first following the screening visit and prior to randomisation, and second after the 12-week follow-up period. Safety was assessed by the number of participants experiencing adverse events (AEs) and serious adverse events (SAEs). For the translational research, stool samples were taken from participants at baseline and then at 2 weekly intervals throughout the study to assess microbiome diversity (by 16S rRNA sequencing) and to examine the effect of FMT on faecal calprotectin. Donor stool samples were also analysed by 16S rRNA sequencing. Biopsy samples were taken from the colon at the time of endoscopy (baseline and week 8) to analyse mucosa-associated microbiome by 16S rRNA sequencing. SCFA levels in stool samples were also measured throughout the study and blood was taken from participants to look for changes in C-reactive protein (CRP) in response to FMT. Donors were asked to fill in a dietary questionnaire in order to look for associations between dietary components in their habitual diet and the efficacy of their donated FMT samples. Results Thirty patients with UC were randomised between March 2018 and April 2019; 16 to NG; 14 to COLON route. Seven participants in the NG arm and two participants in the colonic arm withdrew from the study. Clinical response was achieved in a higher proportion of participants in the colonic arm [9/12 (75%)] compared with the NG arm [2/8 (25%)]; [adjusted risk ratio 2.94 (95% confidence interval, 0.84 to 10.30)]. In the colonic arm, 12/14 (86%) participants were considered adherent compared with 8/16 (50%) in the NG arm. AEs were reported in 11/14 (79%) participants in the colonic arm and 11/16 (69%) in the NG arm. There were three SAEs in two participants in the NG arm, and none in the colonic arm. Qualitative research found a high level of enthusiasm for the trial among both patients and staff. Patients were more positive about the colonic treatment route than the NG route, both before randomisation and after the patients had been through the study. Lower calprotectin levels, implying reduced colonic inflammation, averaged over the last half of the treatment course (weeks 4, 6 and 8), were seen in the responders (N = 11, mean 508.6 mg/kg) versus the non-responders (N = 9, mean 853.6 mg/kg) (p = 0.03). Furthermore, there was a negative association between faecal microbiome alpha diversity [rarefied total operational taxonomic unit (OTU) richness] and calprotectin levels (p < 0.01). This is the first time that change in faecal calprotectin, a widely used clinical inflammatory biomarker in UC, has been reported in response to FMT in inflammatory bowel disease (IBD). With respect to SCFAs, there were significant and large increases observed in the concentration of acetate (45% increase, p = 0.05) and butyrate (57% increase, p = 0.03) across all participants (N = 19) from baseline to week 2 following FMT treatment. This effect was also observed over the course of the entire FMT treatment period from baseline to 8 weeks (N = 16, acetate 21% increase, p = 0.02; butyrate 39% increase, p = 0.08). Significant changes were not observed for the other SCFAs measured, notably propionate (2 weeks p = 0.46, 8 weeks p = 0.36). The observed increase in acetate and butyrate was not associated with clinical response, and in fact when restricted to the responder group (N = 9) changes at both 2 and 8 weeks were no longer significant, although increases were still observed. Across all participants that completed FMT to day 56, and for whom baseline and week 8 DNA was available (N = 13), there was no significant change in faecal microbiome alpha diversity, as measured by rarefied Shannon diversity of 3% OTUs (p = 0.43). However, when restricted to the colonic arm only (N = 8), there was a significant increase in alpha diversity (p = 0.01) observed after FMT. Again, for those participants in the colonic arm that responded to FMT, there was a significant increase in alpha diversity (rarefied Shannon diversity, p < 0.01) compared to those who did not. No differences were seen in alpha diversity of mucosa-associated bacteria pre and post treatment. Donor microbiome diversity, as measured by rarefied 16S rRNA gene Shannon diversity, varied substantially between donors. There was a non-significant positive association between clinical response and donor diversity (p = 0.19) with the treatment arm taken into account. In this pilot study, CRP values were lower at baseline in the colonic arm (4.2 mg/l) compared with the NG arm (11.3 mg/l). Similarly, CRP values at weeks 4, 6 and 8 were also lower in the colonic arm than in the NG arm. With regard to data derived from diet questionnaires administered to donors, higher milk and milk product intakes were associated with higher alpha diversity, but this was not statistically significant. The mean number of days from stool donation to FMT treatment was similar in participants who achieved a clinical response compared with those who did not achieve a clinical response. There was no association between time from stool donation and treatment, and clinical response when added to the primary intention-to-treat analysis model. Conclusion This pilot study suggests that in patients with active UC, FMT delivered via the colonic route appears to be safe and better tolerated with signals suggesting greater efficacy compared to the NG route. The pilot study was welcomed by patients and clinicians, and FMT appears, at least in the short term, to be safe and well tolerated. On review of these data, the Independent Oversight Committee recommended progressing to the planned placebo-controlled randomised trial, which would be powered to assess efficacy, and would have enabled more detailed mechanistic studies to assess for strains engrafting from donors to recipients, which are associated with clinical response. Patients remain very interested in FMT as a potential treatment for UC as this microbiome manipulation affords an alternative therapy to immune system suppression as a means to treat UC. The trial management group involved in this pilot believe that further studies to assess the efficacy of FMT in UC with a focus on understanding mechanisms are warranted as the first step towards developing precision live biotherapeutics for IBD. Trial registration This trial is registered as ISRCTN74072945 and EudraCT 2015-005753-12. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 13/179/01) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 14. See the NIHR Funding and Awards website for further award information.

ABSTRACT Clostridioides difficile infection (CDI) is a major cause of healthcare-associated diarrhea, despite the widespread implementation of contact precautions for patients with CDI. Here, we investigate strain contamination in a hospital setting and the genomic determinants of disease outcomes. Across two wards over 6 months, we selectively cultured C. difficile from patients (n = 384) and their environments. Whole-genome sequencing (WGS) of 146 isolates revealed that most C. difficile isolates were from clade 1 (131/146, 89.7%), while only one isolate of the hypervirulent ST1 was recovered. Of culture-positive admissions (n = 79), 19 (24%) patients were colonized with toxigenic C. difficile on admission to the hospital. We defined 25 strain networks at ≤2 core gene single nucleotide polymorphisms; two of these networks contain strains from different patients. Strain networks were temporally linked (P < 0.0001). To understand the genomic correlates of the disease, we conducted WGS on an additional cohort of C. difficile (n = 102 isolates) from the same hospital and confirmed that clade 1 isolates are responsible for most CDI cases. We found that while toxigenic C. difficile isolates are associated with the presence of cdtR, nontoxigenic isolates have an increased abundance of prophages. Our pangenomic analysis of clade 1 isolates suggests that while toxin genes (tcdABER and cdtR) were associated with CDI symptoms, they are dispensable for patient colonization. These data indicate that toxigenic and nontoxigenic C. difficile contamination persist in a hospital setting and highlight further investigation into how accessory genomic repertoires contribute to C. difficile colonization and disease.IMPORTANCEClostridioides difficile infection remains a leading cause of hospital-associated diarrhea, despite increased antibiotic stewardship and transmission prevention strategies. This suggests a changing genomic landscape of C. difficile. Our study provides insight into the nature of prevalent C. difficile strains in a hospital setting and transmission patterns among carriers. Longitudinal sampling of surfaces and patient stool revealed that both toxigenic and nontoxigenic strains of C. difficile clade 1 dominate these two wards. Moreover, quantification of transmission in carriers of these clade 1 isolates underscores the need to revisit infection prevention measures in this patient group. We identified unique genetic signatures associated with virulence in this clade. Our data highlight the complexities of preventing transmission of this pathogen in a hospital setting and the need to investigate the mechanisms of in vivo persistence and virulence of prevalent lineages in the host gut microbiome.

Abstract Background and Aim To evaluate the demographic and prognostic significance of gastrointestinal (GI) symptoms in patients with coronavirus disease 2019 (COVID‐19). Methods A systematic search of electronic information sources was conducted. Combined overall effect sizes were calculated using random‐effects models for baseline demographic factors and outcomes including mortality, intensive care unit (ICU) admission, and length of hospital stay. Results Twenty‐four comparative observational studies reporting a total of 51 522 COVID‐19 patients with (n = 6544) or without (n = 44 978) GI symptoms were identified. The patients with GI symptoms were of comparable age (mean difference [MD]: 0.25, 95% confidence interval [CI] −2.42 to 2.92, P = 0.86), rate of pre‐existing hypertension (odds ratio [OR]: 1.11, 95% CI 0.86–1.42, P = 0.42), diabetes mellitus (OR: 1.14, 95% CI 0.91–1.44, P = 0.26), and coronary artery disease (OR: 1.00, 95% CI 0.86–1.16, P = 0.98) compared with those without GI symptoms. However, there were significantly more male patients in the GI symptoms group (OR: 0.85, 95% CI 0.75–0.95, P = 0.005). The presence of GI symptoms was associated with similar risk of mortality (OR: 0.73; 95% CI 0.47–1.13, P = 0.16), ICU admission (OR: 1.15; 95% CI 0.67–1.96, P = 0.62), and length of hospital stay (MD: 0.43; 95% CI −0.73 to 1.60, P = 0.47) when compared with their absence. Conclusion Meta‐analysis of the best possible available evidence demonstrated that GI symptoms in COVID‐19 patients do not seem to affect patients with any specific demographic patterns and may not have any important prognostic significance. Although no randomized studies can be conducted on this topic, future high‐quality studies can provide stronger evidence to further understand the impact of GI symptoms on outcomes of COVID‐19 patients.

Abstract The threadfin Eleutheronema are the important fishery resources in Indo-Pacific regions and classified as the endangered species with considerable conservation values. Their genetic diversity and population structure remain essentially unknown but are critical for the proper management and sustainable harvests of such important fisheries. Here, the mitochondrial DNA sequences of CO1 and 16s rRNA were determined from 75 individuals of Eleutheronema tetradactylum and 89 individuals of Eleutheronema rhadinum collected from different locations of South China Sea and Thailand coastal waters. Genetic diversity analysis revealed that both E. tetradactylum (Haplotype diversity, H = 0.105–0.211; Nucleotide diversity, π = 0.00017–0.00043) and E. rhadinum (H = 0.074–0.663, π = 0.00013–0.01088) had low diversity. Population structure analysis demonstrated the shallow genetic differentiation among the South China Sea populations. The limited communication between China and Thailand populations caused the high genetic differentiation in all groups due to the low dispersal ability. Reconstruction of CO1 phylogenetic relationships and demographic studies across Indo-West-Pacific regions provided strong evidence for a shared common origin or ancestor of E. tetradactylum and E. rhadinum. Eleutheronema rhadinum were further subdivided into two distinct genetic lineages, with Clade A dominantly distributing in Thailand and Malaysia and Clade B distributing in China coastal waters. Phenotypic divergence, characterized mainly by the depth of caudal peduncle and length of caudal peduncle, was also observed for all populations, which was possibly associated with specific local adaptations to environmental changes. Our study suggested a strong need for the development of proper fishery management strategies and conservation actions for the imperiled Eleutheronema species.

Category: Diabetes Introduction/Purpose: Complex foot and ankle deformities secondary to charcot neuroarthropathy continue to represent a significant challenge and management quandary. This is due to the combination of medical co-morbidities, peripheral neuropathy, immune compromise, and micro/macro vascular issues in addition to the surgical challenge of wide area of injury, progressive deformity and bone resorption. The technique of 'superconstructs' have been proposed as a method of combating these challenges with deformity correction achieved through fusion out with the zone of injury and fixation in unaffected 'normal' bone. We present here the outcomes of this technique at one year using internal fixation alone, external fixation alone and the novel technique of combined internal and external fixation using combined internal and external fixation internal/ external fixation only at one year. Methods: Retrospective two-surgeon case series with all cases jointly operated upon. Cases identified from a locally held charcot patient registry. Patients undergoing charcot foot and ankle reconstruction from 2017 to 2020 included. No exclusion criteria outlined. Patient demographics and comorbidities were collected, pre-op radiological markers (meary's angle) measured and repeated at 6-12 /52 and 1 year. Patient outcomes were recorded of ulcer recurrence, limb salvage, pain score, stable heel, able to ambulate, need for revision surgery, fusion and surgical complications. Proms are awaited for all patients. Results: 19 cases from 18 patients undergoing reconstruction identified. 18 cases were included for analysis. Fourteen patients were broadsky 1, one broadsky 2, one broadsky 3 and two broadsky 4. 3 patients had internal fixation, 5 external fixation and 10 combined internal and external fixation. Limb salvage was 94% with one amputation. Mortality rate was nil. All patients reported improved pain scores, a stable heel and were ambulating. No recurrence of ulceration reported and no prolonged antibiotic use. Mearys angle improved in all groups: Internal fixation pre-op -9.6o, post op 2.6o and 1 year -1o, external fixation pre-op -20o, post op -6o and 1 year -12o, IF + EF pre-op -24.6o, post op 1.2o and 1 year -2.3o. Fusion rate was 100% with average time to fusion 154 days and a range of 360 - 52. Complications of 2 tibial fractures and metalwork removal with delayed wound healing were noted. Conclusion: The outcome of all three methods is positive with 94% limb salvage, 100% fusion / ambulation/ improved pain and ulcer free at 1 year. Mearys angle is improved at one year however there is a loss of correction noted with external fixation alone. These results are encouraging and support the use of combined internal and external fixation in these complex cases. The added benefit of this technique of maintaining ambulation, avoiding the complications of nonweightbearing all whilst maintaining the structure of the reconstructed foot are promising. The complications reported were in the first 3 patient and represent a learning curve.

Summary: Background: Faecal microbiota transplantation (FMT) has previously been explored as a treatment for ulcerative colitis (UC) however, biomarkers that predict and / or are associated with clinical response are poorly defined. The aim of this systematic review was to identify donor and recipient clinical, microbial and metabolomic predictive biomarkers of response to FMT in UC. Methods: A systematic search of the relevant literature of studies exploring FMT in UC was conducted. Data on microbial diversity, taxonomic changes, metabolic changes, donor and recipient microbiota relationship and baseline predictors was examined. Findings: 2852 studies were screened, and 25 papers were included in this systematic review. Following FMT, alpha diversity was seen to increase in responders along with increases in the abundance of Clostridiales clusters (order) and Bacteroides genus. Metabolomic analysis revealed short chain fatty acid (SCFA) production as a marker of FMT success. Donors or FMT batches with higher microbial alpha diversity and a greater abundance of taxa belonging to certain Bacteroides and Clostridia clusters were associated with clinical response to FMT. Baseline clinical predictors of response in patients with UC included younger age, less severe disease and possibly shorter disease duration. Baseline recipient microbial predictors at response consisted of higher faecal species richness, greater abundance of Candida and donor microbial profile similarity. Interpretation: Distinct changes in gut microbiota profiles post-FMT indicate that certain baseline characteristics along with specific microbial and metabolomic alterations may predispose patients towards a successful therapeutic outcome. Opportunities towards a biomarker led precision medicine approach with FMT should be explored in future clinical studies. Funding: There no specific funding to declare.

ABSTRACT A total of 1500 day old broiler chicks were grouped into five treatments; each treatment group further consisted of six replicates. Group A was given a control diet having antibiotics. Group B and C were offered essential oil blend at the proportion of 0.1 g/kg and organic acid at the dose rate of 1g/kg. Group D was given both essential oil 0.1 g/kg and organic acid 1g/kg in combination. Group E was offered only a basal diet without antibiotics and considered as a negative control. The trial lasted for 35 days. Results indicated that the body weight gain and feed conversion ratio (FCR) exhibited significant improvement but insignificant in the case of feed consumption. Bodyweight and FCR were better in group B, followed by C. Carcass characteristics like eviscerated weight and giblet weight were also improved in group B while dressed weight showed insignificant results. Total cholesterol and high-density lipoproteins (HDL) were unaffected by the treatments; however, increased blood glucose levels and decreased low-density lipoproteins (LDL) concentration were significantly noticed. Treatment groups have no effect on antibody titer against ND at the end of the trial. In gut morphology, significantly higher villus height was observed in group C, but villus width and crypt depth remained unaffected. In conclusion, essential oil and organic acids have improved performance, carcass parameters, serum biochemistry, gut health, and decreased bacterial count.

This manuscript retrieve lump soliton solution for geophysical Korteweg–de Vries equation (GKdVE) with the help of Hirota bilinear method (HBM). We will also obtain lump–kink soliton (which is interaction of lump with one kink soliton), lump-periodic solutions (which is formed by interaction between periodic waves and lump) and lump–kink-periodic solutions (which is formed by interaction of periodic waves and lump with one kink soliton). The dynamics of these solution are examined graphically by selecting significant parameters.

Category: Diabetes; Trauma Introduction/Purpose: Management of complex foot and ankle deformities secondary to charcot neuroathropathy represents a significant challenge. This is a consequence of medical co-morbidities, vascular disease, peripheral neuropathy, and immune compromise with the surgical challenges of progressive bony defomity and bone resorption. To combat these challenges ‘superconstructs’ have been developed to improve fixation. These aim for fusion beyond the zone of injury with adequate deformity correction all whilst maintaining viability of the soft tissue envelope and mechanical function. This can be achieved with internal fixation using indication specific plates and beaming techniques, external fixation with a circular frame or a combination of the two. The aim of this study was to evaluate of a tertiary referral hospital in the operative management of charcot neuroarthopathy. Methods: This is a retrospective two surgeon case series with all cases jointly operated upon. Cases were identified from a locally held diabetic patient registry as those undergoing charcot foot and ankle reconstruction from 2017 to 2019. No exclusion criteria were outlined. Patient demographics and co-morbidities were collected, pre-op radiological markers (meary’s angle) measured and repeated at 6 weeks and one year. Pre-op radiographs were classifed accroding to brodsky classification. Patient outcomes were recorded of amputation, mortality, ulcer recurrence, reported pain, stable heel, ability to ambulate, need for revision surgery, need for prolonged antibiotics, fusion and surgical complications. PROMS were requested and still awaited at time of submission. Results: Eleven Cases were identified from ten patients, all were included for analysis. Three patients had internal fixation, two had external fixation and six had combined internal with external fixation. Eight patients were Brodsky 1, two patients were Brodsky 3 and one patient was Brodsky 2. Limb salvage was 100% with nil amputations, mortality 0%, ulcer recurrence 0%, 100% improved pain score, and 100% with a stable heel. Meary’s angle improved by a mean of 14o from -16o to -2o at 1 year. Fusion rate determined clinically and radiologically with X-ray was 100% with mean of 129 days and range of (360 - 52). Mean follow-up 454 days and range (547-417). Complications of 2 tibial fractures and 1 deep infection with delayed wound healing. Conclusion: The outcomes of using all three methods is positive with 100% limb salvage, 100% fusion rate, 100% ulcer free and maintenace of Meary’s angle at 1 year post op. We believe that combined internal and external fixation, not widely reported in the literature, is a good option in these cases. The complications reported here were in the first three patients undergoing said technique and represent a learning curve.

Faecal microbiota transplant (FMT) has now been established into clinical guidelines for the treatment of recurrent and refractory Clostridioides difficile infection (CDI). Its therapeutic application in inflammatory bowel disease (IBD) is currently at an early stage. To date, there have been four randomized controlled trials for FMT in IBD and a multitude of observational studies. However, significant gaps in our knowledge regarding optimum methods for FMT preparation, technical aspects and logistics of its administration, as well as mechanistic underpinnings, still remain. In this article, we aim to highlight these gaps by reviewing evidence and making key recommendations on the direction of future studies in this field. In addition, we provide an overview of the current evidence of potential mechanisms of FMT in treating IBD.

It is clear from epidemiological studies that excess iron is associated with increased risk of colorectal cancer; however, questions regarding the mechanism of how iron increases cancer risk, the source of the excess iron (circulating or luminal), and whether iron reduction represents a potential therapeutic option remain unanswered. In this study, we show that after Apc deletion, the cellular iron acquisition proteins TfR1 and DMT1 are rapidly induced. Conversely, restoration of APC reduces cellular iron due to repression of these proteins. To test the functional importance of these findings, we performed in vivo investigations of the impact of iron levels on intestinal tumorigenesis. Strikingly, depletion of luminal (but not systemic) iron strongly suppressed murine intestinal tumorigenesis, whereas increased luminal iron strongly promoted tumorigenesis. Taken together, our data definitively delineate iron as a potent modifier of intestinal tumorigenesis and have important implications for dietary iron supplementation in patients at high risk of colorectal cancer.

Dengue and chikungunya are rapidly expanding viruses transmitted by mosquitoes of the genus Aedes. Few epidemiological studies have examined the extent of transmission of these infections in South India despite an increase in the number of reported cases, and a high suitability for transmission.We conducted a household-based seroprevalence survey among 1010 individuals aged 5-40 years living in fifty randomly selected spatial locations in Chennai, Tamil Nadu. Participants were asked to provide a venous blood sample and to complete a brief questionnaire with basic demographic and daily activity information. Previous exposure to dengue and chikungunya was determined using IgG indirect ELISA (Panbio) and IgG ELISA (Novatec), respectively. We used this data to estimate key transmission parameters (force of infection and basic reproductive number) and to explore factors associated with seropositivity. While only 1% of participants reported history of dengue and 20% of chikungunya, we found that 93% (95%CI 89-95%) of participants were seropositive to dengue virus, and 44% (95%CI 37-50%) to chikungunya. Age-specific seroprevalence was consistent with long-tem, endemic circulation of dengue and suggestive of epidemic chikungunya transmission. Seropositivity to dengue and chikungunya were significantly correlated, even after adjusting for individual and household factors. We estimate that 23% of the susceptible population gets infected by dengue each year, corresponding to approximately 228,000 infections. This transmission intensity is significantly higher than that estimated in known hyperendemic settings in Southeast Asia and the Americas.These results provide unprecedented insight into the very high transmission potential of dengue and chikungunya in Chennai and underscore the need for enhanced surveillance and control methods.

Alginates are a class of biopolymers with known iron binding properties which are routinely used in the fabrication of iron-oxide nanoparticles. In addition, alginates have been implicated in influencing human iron absorption. However, the synthesis of iron oxide nanoparticles employs non-physiological pH conditions and whether nanoparticle formation in vivo is responsible for influencing cellular iron metabolism is unclear. Thus the aims of this study were to determine how alginate and iron interact at gastric-comparable pH conditions and how this influences iron metabolism. Employing a range of spectroscopic techniques under physiological conditions alginate-iron complexation was confirmed and, in conjunction with aberration corrected scanning transmission electron microscopy, nanoparticles were observed. The results infer a nucleation-type model of iron binding whereby alginate is templating the condensation of iron-hydroxide complexes to form iron oxide centred nanoparticles. The interaction of alginate and iron at a cellular level was found to decrease cellular iron acquisition by 37% (p < 0.05) and in combination with confocal microscopy the alginate inhibits cellular iron transport through extracellular iron chelation with the resulting complexes not internalised. These results infer alginate as being useful in the chelation of excess iron, especially in the context of inflammatory bowel disease and colorectal cancer where excess unabsorbed luminal iron is thought to be a driver of disease.