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Background: Corticosteroids are used for induction of remission in patients with moderately to severely active ulcerative colitis. However, up to one-third of patients fail to this therapy. We investigated if fecal microbial composition or its metabolic capacity are associated with response to systemic corticosteroids., Methods: In this prospective, multicenter study, patients with active ulcerative colitis (Lichtiger score ≥4) receiving systemic corticosteroids were eligible. Data were assessed and fecal samples collected before and after 4 weeks of treatment. Patients were divided into responders (decrease of Lichtiger Score ≥50%) and nonresponders. The fecal microbiome was assessed by the 16S rRNA gene marker and analyzed with QIIME 2. Microbial metabolic pathways were predicted using parsimonious flux balance analysis., Results: Among 93 included patients, 69 (74%) patients responded to corticosteroids after 4 weeks. At baseline, responders could not be distinguished from nonresponders by microbial diversity and composition, except for a subgroup of biologic-naïve patients. Within 4 weeks of treatment, responders experienced changes in beta diversity with enrichment of ascribed beneficial taxa, including Blautia, Anaerostipes, and Bifidobacterium, as well as an increase in predicted butyrate synthesis. Nonresponders had only minor longitudinal taxonomic changes with a significant increase of Streptococcus salivarius and a microbial composition shifting away from responders., Conclusion: Baseline microbial diversity and composition seem to be of limited use to predict response to systemic corticosteroids in active ulcerative colitis. Response is longitudinally associated with restoration of microbial composition and its metabolic capacity., (© 2023 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Objectives: In infants with suspected food protein induced proctocolitis (sFPIP) only a minority of patients are finally diagnosed with the disease following diagnostic dietary intervention (DDI). There is a need for a pathophysiological explanation for the cause of hematochezia in the majority of sFPIP infants., Methods: We prospectively recruited infants with sFPIP and healthy controls. Fecal samples were collected at inclusion, week 4 (end of DDI in sFPIP), and week 8. For 16S rRNA sequencing (515F/806R) we used Illumina MiSeq sequencing system. Amplicon sequence variants were generated using Qiime2 and DADA2. Qiime diversity alpha and beta group comparisons and linear discriminant analysis effect size analysis was performed. For shotgun metagenomic analysis on species level we used KneadData and MetaPhlAn2., Results: Fourteen sFPIP infants were compared to 55 healthy infants. At inclusion overall microbial composition of sFPIP infants differed significantly from controls (weighted UniFrac; Pairwise PERMANOVA, P = 0.002, pseudo- F = 5.008). On genus level healthy infant microbiota was significantly enriched with Bifidobacterium ( B ) compared to sFPIP patients (linear discriminant analysis [LDA] = 5.5, P < 0.001, 31.3% vs 12.1%). sFPIP stool was significantly enriched by Clostridium sensu stricto 1 over controls (LDA = 5.3, P = 0.003, 3.5% vs 18.3%). DDI caused a significant and sustained increase of Bifidobacterium (LDA = 5.4, P = 0.048, 27.9%) in sFPIP infants. Species level analysis revealed significant reduction of abundance of B longum in sFPIP patients, which after DDI was reversed by B. species other than B longum ., Conclusions: We revealed a gut microbiota dysbiosis phenomenon in sFPIP infants. DDI induces a microbiota composition comparable to that of healthy infants. In most sFPIP infants hematochezia might be triggered by a gut microbiota dysbiosis phenomenon., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Secondary infections contribute significantly to covid-19 mortality but driving factors remain poorly understood. Autopsies of 20 covid-19 cases and 14 controls from the first pandemic wave complemented with microbial cultivation and RNA-seq from lung tissues enabled description of major organ pathologies and specification of secondary infections. Lethal covid-19 segregated into two main death causes with either dominant diffuse alveolar damage (DAD) or secondary pneumonias. The lung microbiome in covid-19 showed a reduced biodiversity and increased prototypical bacterial and fungal pathogens in cases of secondary pneumonias. RNA-seq distinctly mirrored death causes and stratified DAD cases into subgroups with differing cellular compositions identifying myeloid cells, macrophages and complement C1q as strong separating factors suggesting a pathophysiological link. Together with a prominent induction of inhibitory immune-checkpoints our study highlights profound alterations of the lung immunity in covid-19 wherein a reduced antimicrobial defense likely drives development of secondary infections on top of SARS-CoV-2 infection., Competing Interests: H.L. is founder of Alacris Theranostics GmbH and M.S. and L.O. are employees of Alacris Theranostics GmbH. K. Z. is CEO and founder of Zatloukal Innovations GmbH. All other authors declare no conflicts of interest., (© 2022 The Authors.)

The SARS-CoV-2 pandemic has highlighted the interdependency of healthcare systems and research organizations on manufacturers and suppliers of personnel protective equipment (PPE) and the need for well-trained personnel who can react quickly to changing working conditions. Reports on challenges faced by research laboratory workers (RLWs) are rare in contrast to the lived experience of hospital health care workers. We report on experiences gained by RLWs (e.g., molecular scientists, pathologists, autopsy assistants) who significantly contributed to combating the pandemic under particularly challenging conditions due to increased workload, sickness and interrupted PPE supply chains. RLWs perform a broad spectrum of work with SARS-CoV-2 such as autopsies, establishment of virus cultures and infection models, development and verification of diagnostics, performance of virus inactivation assays to investigate various antiviral agents including vaccines and evaluation of decontamination technologies in high containment biological laboratories (HCBL). Performance of autopsies and laboratory work increased substantially during the pandemic and thus led to highly demanding working conditions with working shifts of more than eight hours working in PPE that stressed individual limits and also the ergonomic and safety limits of PPE. We provide detailed insights into the challenges of the stressful daily laboratory routine since the pandemic began, lessons learned, and suggest solutions for better safety based on a case study of a newly established HCBL (i.e., BSL-3 laboratory) designed for autopsies and research laboratory work. Reduced personal risk, increased resilience, and stress resistance can be achieved by improved PPE components, better training, redundant safety measures, inculcating a culture of safety, and excellent teamwork., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Loibner, Barach, Wolfgruber, Langner, Stangl, Rieger, Föderl-Höbenreich, Hardt, Kicker, Groiss, Zacharias, Wurm, Gorkiewicz, Regitnig and Zatloukal.)

Objectives: Klebsiella oxytoca is a gastrointestinal pathobiont with the potential to produce the toxins tilivalline and tilimycin, which cause antibiotic-associated hemorrhagic colitis. Overgrowth of toxigenic K oxytoca has recently been implicated in necrotizing enterocolitis. K oxytoca colonizes 2-9% of healthy adults, however, there is no systematic data on colonization in healthy children. We investigated K oxytoca colonization and its toxigenic properties in healthy infants., Methods: We sampled stool of healthy infants and determined K oxytoca colonization using stool culture and PCR (pehX). Toxin in stool was measured with HPLC/high-resolution mass spectrometry. K oxytoca isolates were typed using multi-locus sequence typing (MLST) and K oxytoca toxin PCR (npsA/B). Cytotoxin production of isolates was analyzed by MTT assay., Results: K oxytoca was detected in 30 of 61 infants (49%) using stool culture and in 45 of 61 (73%) using PCR (pehX). Toxin marker PCR (npsA/B) was positive in 66% of stool samples positive for K oxytoca PCR. Stool toxin levels were too low for quantitation but traces of tilivalline were detected. Contrarily, 49% of K oxytoca isolates demonstrated toxicity in the MTT assay. MLST revealed 36 distinct sequence types affiliated with all known K oxytoca sequence type clusters (A, B1 and B2)., Conclusions: More than 70% of healthy infants were colonized with K oxytoca. Toxin quantities in stool of colonized healthy infants were below detection level, yet half of the isolates produced toxin in vitro demonstrating their pathobiont potential. The high occurrence of toxigenic K oxytoca in healthy infants has to be considered for future disease association studies., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Detecting severe acute respiratory syndrome coronavirus 2 in deceased patients is key when considering appropriate safety measures to prevent infection during postmortem examinations. A prospective cohort study comparing a rapid antigen test with quantitative reverse transcription PCR showed the rapid test's usability as a tool to guide autopsy practice.

Competing Interests: Competing interests: None declared.

Molecular techniques including the sequencing of fungal-specific DNA targets are increasingly used in the diagnosis of suspected invasive fungal infections. In contrast to established biomarkers like galactomannan or 1-3-β-d-glucan, the clinical impact of these methods remains unknown. We retrospectively investigated the impact of ITS1-sequencing on antifungal treatment strategies in 71 patients (81 samples) with suspected invasive fungal infections. ITS-sequencing either confirmed already ongoing antifungal therapy (19/71 patients, 27%), led to a change in antifungal therapy (11/71, 15%) or supported the decision to withhold antifungal treatment (34/71, 48%) (in seven of 71 patients, ITS-sequencing results were obtained postmortem). ITS-sequencing results led to a change in antifungal therapy in a relevant proportion of patients, while it confirmed therapeutic strategies in the majority. Therefore, ITS-sequencing was a useful adjunct to other fungal diagnostic measures in our cohort., Competing Interests: The authors declare no conflict of interest.

Idiopathic intestinal varicosis is a developmental disorder defined by dilated and convoluted submucosal veins in the colon or small bowel. A limited number of families with idiopathic intestinal varices has been reported, but the genetic cause has not yet been identified. We performed whole-exome and targeted Sanger sequencing of candidate genes in five intestinal varicosis families. In four families, mutations in the RPSA gene were found, a gene previously linked to congenital asplenia. Individuals in these pedigrees had intestinal varicose veins and angiodysplasia, often in combination with asplenia. In a further four-generation pedigree that only showed intestinal varicosities, the RPSA gene was normal. Instead, a nonsense mutation in the homeobox gene NKX2-3 was detected which cosegregated with the disease in this large family with a LOD (logarithm of the odds) score of 3.3. NKX2-3 is a component of a molecular pathway underlying spleen and gut vasculature development in mice. Our results provide a molecular basis for familial idiopathic intestinal varices. We provide evidence for a relationship between the molecular pathways underlying the development of the spleen and intestinal mucosal vasculature that is conserved between humans and mice. We propose that clinical management of intestinal varices, should include assessment of a functional spleen., (© 2019 The Authors. Human Mutation Published by Wiley Periodicals, Inc.)

Background: Endoscopy within 24 h of admission (early endoscopy) is a quality standard in acute upper gastrointestinal bleeding (AUGIB). We aimed to audit time to endoscopy outcomes and identify factors affecting delayed endoscopy (>24 h of admission)., Methods: This prospective multicentre audit enrolled patients admitted with AUGIB who underwent inpatient endoscopy between November and December 2017. Analyses were performed to identify factors associated with delayed endoscopy, and to compare patient outcomes, including length of stay and mortality rates, between early and delayed endoscopy groups., Results: Across 348 patients from 20 centres, the median time to endoscopy was 21.2 h (IQR 12.0-35.7), comprising median admission to referral and referral to endoscopy times of 8.1 h (IQR 3.7-18.1) and 6.7 h (IQR 3.0-23.1), respectively. Early endoscopy was achieved in 58.9%, although this varied by centre (range: 31.0-87.5%, p = 0.002). On multivariable analysis, lower Glasgow-Blatchford score, delayed referral, admissions between 7:00 and 19:00 hours or via the emergency department were independent predictors of delayed endoscopy. Early endoscopy was associated with reduced length of stay (median difference 1 d; p = 0.004), but not 30-d mortality (p = 0.344)., Conclusions: The majority of centres did not meet national standards for time to endoscopy. Strategic initiatives involving acute care services may be necessary to improve this outcome.

Clinical interventions in the stomach have been linked to fecal microbiota alterations, suggesting a function of the stomach in gastrointestinal (GI) homeostasis. We sought to determine the taxonomic bacterial biogeography of the upper GI tract, including different sites within the human stomach (cardia, corpus, and antrum), adjacent upstream (esophagus) and downstream (duodenum) locations, and luminal contents (aspirate), as well as whole-stomach samples from mice and gerbils. Qualitative and quantitative DNA- and RNA-based taxonomic microbiota analyses were combined to study the relationship of relative and absolute bacterial abundances and transcriptionally active bacterial microbiota components in the stomach of humans and mice. Stomach microbiota compositions resembled those of esophagus and duodenum. However, along the descending GI tract, the relative abundances of specific oropharyngeal commensals decreased ( Streptococcus ) or increased (Rothia mucilaginosa, Porphyromonas , and Lachnospiraceae ). Furthermore, the compositional similarity (weighted UniFrac) between stomach aspirates and esophageal biopsy samples increased with gastric Streptococcus relative abundance. In both human aspirate and mouse stomach samples, Firmicutes were more abundant among transcriptionally active bacteria than Bacteroidetes . The relative abundance of Firmicutes in the stomach was negatively correlated and that of Bacteroidetes was positively correlated with absolute bacterial abundance, suggesting a disproportionate increase of Bacteroidetes over Firmicutes at higher bacterial densities. Human, mouse, and gerbil stomach samples showed similarities at higher taxonomic levels but differences at lower taxonomic levels. Our findings suggest selective enrichment and depletion of specific bacterial taxa in the stomach and Firmicutes being transcriptionally more active than Bacteroidetes that increase in relative abundance with total bacterial load. IMPORTANCE Clinical stomach interventions, such as acid inhibition or bypass surgery, have been linked to fecal microbiota alterations. We demonstrate that the stomach microbiota largely overlaps those of adjacent gastrointestinal locations and identify gradual decreases and increases in the relative abundances of specific bacteria within the stomach, suggesting selective enrichment and depletion. Moreover, similarities between stomach and esophagus samples are proportional to the concentrations of Streptococcus ( Firmicutes ) in the stomach. The relative abundance of Firmicutes in the stomach, compared to that of Bacteroidetes , is increased in RNA relative to DNA, indicating higher transcriptional activity. Moreover, increased absolute bacterial loads are associated with decreased relative abundance of Firmicutes and higher relative abundance of Bacteroidetes . Our findings characterize the stomach microbiota as influenced by Bacteroidetes influx against a background of transcriptionally more active Firmicutes. Human, mouse, and gerbil stomach microbiotas differ at lower taxonomic levels, which might affect the utility of these model organisms.

Background: Faecal microbiota transplantation is an experimental approach for the treatment of patients with ulcerative colitis. Although there is growing evidence that faecal microbiota transplantation is effective in this disease, factors affecting its response are unknown., Aims: To establish a faecal microbiota transplantation treatment protocol in ulcerative colitis patients, and to investigate which patient or donor factors are responsible for the treatment success., Methods: This is an open controlled trial of repeated faecal microbiota transplantation after antibiotic pre-treatment (FMT-group, n = 17) vs antibiotic pre-treatment only (AB-group, n = 10) in 27 therapy refractory ulcerative colitis patients over 90 days. Faecal samples of donors and patients were analysed by 16SrRNA gene-based microbiota analysis., Results: In the FMT-group, 10/17 (59%) of patients showed a response and 4/17 (24%) a remission to faecal microbiota transplantation. Response to faecal microbiota transplantation was mainly influenced by the taxonomic composition of the donor's microbiota. Stool of donors with a high bacterial richness (observed species remission 946 ± 93 vs no response 797 ± 181 at 15367 rps) and a high relative abundance of Akkermansia muciniphila (3.3 ± 3.1% vs 0.1 ± 0.2%), unclassified Ruminococcaceae (13.8 ± 5.0% vs 7.5 ± 3.7%), and Ruminococcus spp. (4.9 ± 3.5% vs 1.0 ± 0.7%) were more likely to induce remission. In contrast antibiotic treatment alone (AB-group) was poorly tolerated, probably because of a sustained decrease of intestinal microbial richness., Conclusions: The taxonomic composition of the donor's intestinal microbiota is a major factor influencing the efficacy of faecal microbiota transplantation in ulcerative colitis patients. The design of specific microbial preparation might lead to new treatments for ulcerative colitis., (© 2017 The Authors. Alimentary Pharmacology & Therapeutics Published by John Wiley & Sons Ltd.)

Objective: To investigate immune cells of the colonic mucosa and fecal short-chain fatty acids (SCFAs) in treatment-naive patients with a clinically isolated syndrome (CIS) or early relapsing MS., Methods: In this cross-sectional proof-of-concept study, we obtained mucosal specimens during ileocolonoscopy from 15 untreated patients with CIS/MS and 10 controls. Mucosal immune cells were analyzed by FACS, and gas chromatography-mass spectrometry measurements of stool samples served to determine SCFA., Results: The number of total dendritic cells (DCs), CD103+ tolerogenic DCs, and CD4+25+127-regulatory T cells (Tregs) was significantly reduced in the distal colon of patients with CIS/MS compared with controls, whereas we found no differences in the proximal colon. The patients' fecal samples also showed a substantially lower content of SCFA and especially lower levels of butyrate and acetate., Conclusions: Our findings indicate a disturbed homeostasis of colonic DCs and Tregs in patients with MS which could be associated with colonic SCFA depletion. Although not implying causality, these findings confirm parallel abnormalities of the gut in MS and warrant further research if modulation of the colonic SCFA profile or the colonic Treg pool can serve to modify the course of MS.

Objective: Antibiotic therapy is a major risk factor for the development of diarrhea and colitis with varying severity. Often the origin of antibiotic-associated gastrointestinal deterioration remains elusive and no specific infectious agents could be discerned., Patients: We represent three cases of intractable high-volume diarrhea associated with combined antibiotic and steroid therapy in critically ill patients not fitting into established disease entities. Cases presented with severe apoptotic enterocolitis resembling acute intestinal graft-versus-host-disease. Microbiologic workup precluded known enteropathogens, but microbiota analysis revealed a severely depleted gut microbiota with concomitant opportunistic pathogen overgrowth., Interventions: Fecal microbiota transplantation, performed in one patient, was associated with correction of dysbiosis, rapid clinical improvement, and healing of enterocolitis., Conclusions: Our series represents a severe form of antibiotic-associated colitis in critically ill patients signified by microbiota depletion, and reestablishment of a physiologic gastrointestinal microbiota might be beneficial for this condition.

Vibrio cholerae can colonize the gastrointestinal track of humans and cause the disease cholera. During colonization, the alternative sigma factor, RpoS, controls a process known as "mucosal escape response," defining a specific spatial and temporal response and effecting chemotaxis and motility. In this report, the expression and proteolytic control of RpoS in V. cholerae was characterized. To date, aspects of proteolysis control, the involved components, and proteolysis regulation have not been addressed for RpoS in V. cholerae. Similar to Escherichia coli, we find that the RpoS protein is subjected to regulated intracellular proteolysis, which is mediated by homologues of the proteolysis-targeting factor RssB and the protease complex ClpXP. As demonstrated, RpoS expression transiently peaks after cells are shifted from rich to minimal growth medium. This peak level is dependent on (p)ppGpp-activated rpoS transcription and controlled RpoS proteolysis. The RpoS peak level also correlates with induction of a chemotaxis gene, encoding a methyl-accepting chemotaxis protein, earlier identified to belong to the mucosal escape response pathway. These results suggest that the RpoS expression peak is linked to (p)ppGpp alarmone increase, leading to enhanced motility and chemotaxis, and possibly contributing to the mucosal escape response., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Corpus-dominant lymphocytic gastritis (LyG) is characterized by CD8 + T-cell infiltration of the stomach epithelium by a so far uncharacterized mechanism. Although Helicobacter pylori is typically undetectable in LyG, patients respond to H. pylori antibiotic eradication therapy, suggesting a non-H. pylori microbial trigger for the disease. Comparative microbiota analysis of specimens from LyG, H. pylori gastritis and healthy controls precluded involvement of H. pylori in LyG but identified Propionibacterium acnes as a possible disease trigger. In addition, the natural killer group 2 member D (NKG2D) system and the proinflammatory cytokine interleukin (IL)-15 are significantly upregulated in the gastric mucosa of LyG patients, and gastric epithelial cells respond to microbe-derived stimuli, including live P. acnes and the microbial products short-chain fatty acids, with induction of NKG2D ligands. In contrast, H. pylori infection does not activate or even repress NKG2D ligands. Together, our findings identify P. acnes as a possible causative agent for LyG, which is dependent on the NKG2D system and IL-15 activation. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland., (© 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.)

Purpose: Vitamin D is well known for its effects on bone mineralisation but has also been attributed immunomodulatory properties. It positively influences human health, but in vivo data describing vitamin D effects on the human gut microbiome are missing. We aimed to investigate the effects of oral vitamin D3 supplementation on the human mucosa-associated and stool microbiome as well as CD8(+) T cells in healthy volunteers., Methods: This was an interventional, open-label, pilot study. Sixteen healthy volunteers (7 females, 9 males) were endoscopically examined to access a total of 7 sites. We sampled stomach, small bowel, colon, and stools before and after 8 weeks of vitamin D3 supplementation. Bacterial composition was assessed by pyrosequencing the 16S rRNA gene (V1-2), and CD8(+) T cell counts were determined by flow cytometry., Results: Vitamin D3 supplementation changed the gut microbiome in the upper GI tract (gastric corpus, antrum, and duodenum). We found a decreased relative abundance of Gammaproteobacteria including Pseudomonas spp. and Escherichia/Shigella spp. and increased bacterial richness. No major changes occurred in the terminal ileum, appendiceal orifice, ascending colon, and sigmoid colon or in stools, but the CD8(+) T cell fraction was significantly increased in the terminal ileum., Conclusion: Vitamin D3 modulates the gut microbiome of the upper GI tract which might explain its positive influence on gastrointestinal diseases, such as inflammatory bowel disease or bacterial infections. The local effects of vitamin D demonstrate pronounced regional differences in the response of the GI microbiome to external factors, which should be considered in future studies investigating the human microbiome.

Background: MicroRNAs (miRNAs) are small non-coding RNA molecules. Reduced or increased levels of specific miRNAs are observed in colon and other cancers, supporting their role in carcinogenesis. Detection of colorectal polyps is the cornerstone of the Bowel Cancer Screening Programme in the UK. However, uptake of screening nationally remains under 60%. We aimed to see whether circulating plasma miRNAs can be used to screen for patients with colorectal polyps, adenomas, or both., Methods: Blood samples were taken from patients from the Bowel Cancer Screening Programme (asymptomatic but faecal occult blood testing [FOBt] positive). Plasma RNA was extracted, target miRNAs (19a, 98, 146b, 186, 191, 222*, 331-5p, 452, 625, 664, 1247) were identified on pooled case miRNA assay cards, and miRNA fraction was quantified by quantitative RT-PCR assay. Results were compared with endoscopy reports and with histology of any polyps identified and removed. Analysis was done with Excel (2011) and SPSS (version 20) software., Findings: 210 patients were included (117 with polyps, 12 with cancer, 81 healthy controls [FOBt positive]). The miRNA panel showed significant differences in expression (on t testing) for patients compared with controls for those with polyps, cancer, or both (miR-19a, p=0·0184; miR-98, p=0·0206; miR-146b, p=0·0029; miR-186, p=0·0006; miR-62,5 p=0·0008), polyps (miR-19a, p=0·0233; miR-98, p=0·0224; miR-146b, p=0·003; miR-186, p=0·0004; miR-625, p=0·001), adenomas (miR-19a, p=0·0339; miR-98, p=0·0266; miR-146b, p=0·0045; miR-186, p=0·0008; miR-625, p=0·0049), multiple adenomas (both sides of colon; miR-146b, p=0·0194; miR-186, p=0·0226; miR-625, p=0·0013), and right-sided adenomas (miR-98, p=0·031; miR-146b, p=0·0076; miR-186, p=0·0041; miR-331-5p, p=0·0142; miR-625, p=0·0049). Receiver operating characteristic analysis showed sensitivity of 60% or more, and specificity of 86% or more for men with polyps, men with adenomas, all patients with haemorrhoids or diverticulosis and polyps, and all patients with haemorrhoids or diverticulosis and adenomas., Interpretation: The target miRNAs that we identified showed significant differences in expression levels for patients with polyps and patients with adenomas from controls. Use of this panel has potential as a screening test., Funding: Bowel Disease Research Foundation., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: To evaluate patients' health status and the course of endometriosis from the premenopausal to the postmenopausal period and evaluate influencing factors that may be relevant., Methods: Questionnaire completed by 35 postmenopausal women in whom endometriosis had been histologically confirmed premenopausally. Correlation and regression analyses were carried out to identify factors relevant to their postmenopausal health status., Results: Overall, there was clear improvement in typical endometriosis symptoms and sexual life. Clear associations (P < 0.005) were observed between premenopausal factors like physical limitations caused by the disease, impaired social contacts and psychological problems, and postmenopausal pain and impairment of sexual life. Three statistical models for assessing pain and impairment of sexual life in the postmenopausal period were calculated on the basis of clinical symptoms in the premenopausal period, with a very high degree of accuracy (P < 0.001; R(2) = 0.833/0.857/0.931)., Conclusions: The results of the survey strongly suggest that physical fitness and freedom from physical restrictions, a good social environment, and psychological care in both the premenopausal and postmenopausal periods lead to marked improvements in the postmenopausal period with regard to pain, dyspareunia, and influence on sexual life in endometriosis patients.

Introduction: The British Society of Gastroenterology (BSG) Strategy document 'Care of patients with Gastrointestinal (GI) disorders' recommends that all acute hospitals should have arrangements for out-of-hours (OOH) endoscopy staffed with appropriately trained endoscopists. The UK national audit published in 2010 found that only 52% of hospitals across the UK had a formal consultant-led OOH endoscopy on-call rota. The University Hospitals of Leicester (UHL) established a consultant-led rota in 2006, which now provides 24/7 endoscopy cover. To define the workload of a newly established OOH service, we examined procedures performed since the introduction of an OOH service in 2006., Methods: The audit period covered August-January (6 months) for each of five consecutive years. Data were gathered from formal endoscopy reports on Unisoft reporting tool and OOH record books. We examined indication for endoscopy, timing of procedure, findings at index endoscopy, intervention and immediate outcome., Results: Across the three UHL sites, data on 982 patients were analysed. Eighty-one percent of procedures performed were gastroscopies. 63% of the procedures were performed for GI bleed indications. Over the five years, there was an overall increase in the number of procedures performed where no pathology was found. Immediate outcomes postendoscopy were good, with over 90% being returned to their base ward., Conclusions: The experience at UHL appears to show a trend towards an increasing number of procedures performed OOH, with fewer positive findings and less need for therapy. A likely contributing factor is the ongoing shortage of medical beds, requiring more routine work to be done OOH in order to expedite discharges. However, early specialist endoscopic input is likely to improve patient management. The impact of an OOH service on other services, however, needs to be carefully considered.

Endoscopic mucosal resection is commonly the treatment regime of choice for large sessile colonic polyps. We describe the computed tomography findings of a 51 year old female who presented with transient severe abdominal pain without systemic upset post endoscopic mucosal polyp resection, which resolved with conservative management. This is the second case in the literature that demonstrates 'normal' appearances post endoscopic mucosal resection. The clinical team and radiologist need to be aware of these findings when making management decisions in patients who present with acute pain post endoscopic mucosal resection.

Purpose: The most widely accepted classification for endometriosis is the Revised American Society for Reproductive Medicine (rASRM) system, but this does not take deeply infiltrating endometriosis (DIE) into account. The Enzian classification enables clinicians to classify DIE. Due to complexity and partial overlap with rASRM, it was revised for a second time in February 2011. Using both the systems to classify lesions would be inappropriate, as they refer to different locations. The aim of this study was to analyze whether the revised Enzian classification is easier to use and avoids duplicate classifications., Methods: Retrospective study of 460 women admitted for endometriosis., Results: One hundred and eighty-seven of 460 patients (41 %) had histologically confirmed DIE based on the revised Enzian classification. Further classification of these 187 patients using Enzian revealed 270 retroperitoneal lesions, as some patients had several DIE-type lesions simultaneously: 66 in compartment A (rectovaginal septum, vagina), 112 in compartment B (sacrouterine ligaments, pelvic wall), 58 in compartment C (bowel), 15 with adenomyosis uteri, 7 with bladder involvement, 8 with intrinsic involvement of the ureter, and 4 with bowel involvement. All 270 lesions were classified using Enzian alone and not with the rASRM score. There were no duplicate classifications (rASRM and Enzian)., Conclusions: The revised Enzian classification is an excellent complement to the rASRM score for morphological description of DIE.

Pattern recognition receptors (PRRs) like Toll-like receptors (TLRs) and NOD-like receptors (NLRs) are important sensors of microbial products. Although they are referred to as innate immune receptors, they make essential contributions to adaptive immune responses by activating dendritic cells (DCs). Simultaneous activation of DCs via different classes of PRRs provides a powerful tool for inducing strong immune responses. In the present study we investigate the interplay of the NLRs NOD1 and NOD2 and their crosstalk with TLR signaling in terms of DC-activation. We found strong synergistic effects upon treatment with NOD1 and NOD2 ligands combined with the TLR7/8 agonist R848. Simultaneous stimulation of monocyte-derived DCs resulted in highly increased production of IL-1β, IL-23 and SOCS2, a member of the suppressor of cytokine signaling (SOCS) family. Silencing of SOCS2 resulted in enhanced IL-23 expression, indicating that SOCS2 is involved in the regulation of TLR/NOD-dependent cytokine secretion. Finally, we demonstrate that TLR7/8-, NOD1- and NOD2-activated DCs promote CD4+ T cells to release increased amounts of IL-17. These results demonstrate that cooperative activation of DCs with NOD1 and NOD2 agonists and TLR7/8 ligands results in a synergistic release of pro-inflammatory mediators which promote the activation of IL-17-producing T cells., (Copyright © 2012 Elsevier GmbH. All rights reserved.)

Purpose: The objectives of this study were to examine the age distribution among women suffering from endometriosis and to establish that endometriosis is not a disease that occurs only in premenopausal women. The null hypothesis was that there are also postmenopausal women with endometriosis., Methods: In a retrospective epidemiological study, a descriptive analysis of data from the Federal Statistical Office in Germany for 2005 and 2006 was carried out. A total of 42,079 women in Germany were admitted for surgical treatment due to histologically confirmed endometriosis during this period. The patients' age distribution was examined and they were assigned to 5-year age groups and then to premenopausal, perimenopausal, and postmenopausal subgroups., Results: A total of 20,835 women in 2005 and 21,244 in 2006 were admitted to hospital for the treatment of endometriosis. In the premenopausal group (age 0-45 years), there were 33,814 patients (80.36 %); 23 patients (0.05 %) in this premenopausal group were younger than 15. There were 7,191 patients (17.09 %) in the perimenopausal group (45-55 years), and the postmenopausal group (55-95 years) included 1,074 patients (2.55 %)., Conclusions: The assumption that endometriosis is a disease of the premenopausal period and in women of reproductive age needs to be called into question, as well as the influence of estrogen in fully developed endometriosis. Due to the relatively high prevalence of the condition in patients aged over 40, physicians should consider endometriosis in cases of unclear pelvic pain in this age group.

Objective: Colonoscopy is the 'gold standard' assessment for large bowel mucosal pathology, but a complete examination is essential. The first national colonoscopy audit carried out in 1999 demonstrated caecal intubation rates (CIRs) of 56.9%. As a result, the Joint Advisory Group (JAG) on gastrointestinal endoscopy launched a programme of continuous quality improvement. JAG recommends that practitioners undertake 100+ procedures per annum with a target CIR of 90%. This current audit provides an assessment of performance against this quality standard., Design: Data were collected from all procedures undertaken in 2008-2009 from six hospitals across three English regions., Results: 16064 colonoscopies performed: CIR = 90.57% (95% CI 90.11% to 91.01%). Operators doing 100+ procedures per annum, CIR=91.76% (91.24% to 92.25%). Operators doing <100 procedures per annum, CIR=87.77% (86.82% to 88.67%). Gastroenterologists, CIR=91.01% (90.32% to 91.70%). Surgeons, CIR=91.03% (90.27% to 91.79%). Other practitioners, CIR=81.51% (78.79% to 84.22%). Bowel cancer screening programme (BCSP) colonoscopies, CIR=97.71% (97.07% to 98.34%). Non-screening colonoscopies, CIR=88.31% (95% CI 87.68% to 88.94%)., Conclusion: This audit of 16064 colonoscopies across three regions demonstrates aggregated achievement of the CIR quality standard. However, there is a significant performance gap when comparing BCSP colonoscopists with non-screening colonoscopists and the overall CIR of >90% is supported by the volume of BCSP colonoscopy. Endoscopists performing low volume colonoscopy (<100 per annum), have CIR of <90%. Endoscopists with low volume practice who do not meet the quality standards should engage in skills augmentation plus further training and increase volume of colonoscopy with local mentorship, or stop performing colonoscopy., Competing Interests: Competing interests: None.

Pyogenic liver abscess (PLA) is a rare extraintestinal complication of Crohn's disease (CD), and the clinical and laboratory findings may emulate the reactivation of CD, therefore, delaying diagnosis. In this paper the patient presented with PLA as the initial manifestation of CD and experienced severe disease. The finding of PLA was established by computed tomography and initial treatment involved percutaneous drainage and antibiotics. The diagnosis of CD was made after colonoscopy and histological investigations.

We report on an exclusive and kinematically complete high-statistics measurement of the basic double-pionic fusion reaction pn→dπ(0)π(0) over the full energy region of the ABC effect, a pronounced low-mass enhancement in the ππ-invariant mass spectrum. The measurements, which cover also the transition region to the conventional t-channel ΔΔ process, were performed with the upgraded WASA detector setup at COSY. The data reveal the Abashian-Booth-Crowe effect to be uniquely correlated with a Lorentzian energy dependence in the integral cross section. The observables are consistent with a narrow resonance with m=2.37  GeV, Γ≈70  MeV and I(J(P))=0(3(+)) in both pn and ΔΔ systems. Necessary further tests of the resonance interpretation are discussed.

Objective: To develop a classification that takes deep infiltrating endometriosis into account, the ENZIAN score was introduced. The ENZIAN classification supplements the revised American Fertility Society (AFS) score with regard to the description of deep infiltrating endometriosis, retroperitoneal structures, and other organs. The null hypothesis was that classifying a lesion by the revised AFS as well as the ENZIAN system is not meaningful, because the two systems express different locations., Design: Retrospective., Setting: Hospital admissions., Patient(s): Two hundred nineteen women admitted for endometriosis., Intervention(s): Surgical interventions., Main Outcome Measure(s): Classification of the severity of endometriosis according to the revised AFS and the ENZIAN classification, focusing on the distribution pattern in deep infiltrating endometriosis, and the identification of duplicate classifications of the same lesions in the revised AFS as well as the ENZIAN systems., Result(s): Deep infiltrating endometriosis was diagnosed in 160 of 219 patients (73%). These patients had 236 lesions of deep infiltrating endometriosis, which were classified by ENZIAN as follows: compartment a (vertical): 26%; compartment b (horizontal): 41%; compartment c (dorsal): 24%; uterine adenomyosis: 4%; bladder disease: 2%; ureter disease: 1%; and bowel disease: 2%. The severity of deep infiltrating endometriosis according to ENZIAN (grades 1 = mild to 4 = severe) was as follows: grade 1: 45%; grade 2: 26%; grade 3: 19%; grade 4: 10%. Fifty-eight patients were classified according to ENZIAN although they did not fulfill the criteria of deep infiltrating endometriosis and had previously been classified according to the revised AFS classification. Adaptation of the ENZIAN score would reduce the diagnoses of deep infiltrating endometriosis by 36% (95% confidence interval [CI] 29%-44%)., Conclusion(s): The ENZIAN score is a helpful aid to describe deep infiltrating endometriosis, but needs to be adapted., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Gastro-oesophageal reflux (GER) and coronary artery disease commonly co-exist. Coronary artery disease patients may mistake GER-induced pain for cardiac pain or GER might provoke angina., Aim: To investigate if GER might contribute to nocturnal/rest chest pain among coronary artery disease patients., Methods: Double-blind placebo-controlled crossover study investigating effect of lansoprazole on chest pain; 125 patients with angiographically proven coronary artery disease enrolled with at least one weekly episode of nocturnal/rest pain, randomized to lansoprazole 30 mg daily or placebo with crossover after 4 weeks. Symptoms recorded and QOL assessed by Nottingham Health Profile Questionnaire; ST segment depression episodes counted from 24 h electrocardiographic monitoring in final week of both periods., Statistical Analysis: ANCOVA with period and carryover analysis., Results: In all, 108 patients completed the study. There was a modest increase in pain-free days on lansoprazole vs. placebo (P < 0.02), with fewer days with pain at rest (P < 0.05) and at night (P < 0.009) on lansoprazole vs. placebo, but no significant differences in ST segment depression episodes (P = 0.64). There was a trend for reduction in the 'physical pain' QOL domain., Conclusions: Among coronary artery disease patients, lansoprazole modestly increases pain-free days and reduces rest/nocturnal pain. As lansoprazole did not affect ST segments, this may be by suppression of GER-provoked pain misinterpreted as angina, rather than acid-provoked ischaemia.

Objective: There is an increased risk of colorectal cancer in patients with inflammatory bowel disease (IBD). The aim of this study was to compare the prevalence of left sided adenomas in patients with IBD aged 55-64 years with a local age matched control population., Method: A review of clinical notes. The prevalence of adenomas in patients with IBD attending for either sigmoidoscopy or colonoscopy was compared with local age matched controls that participated in the national screening trial for colorectal cancer with flexible sigmoidoscopy., Results: Of 106 patients (61 male, 45 female, mean age of 59 years), 80 suffered from ulcerative colitis, 20 from Crohn's disease, and six from indeterminate colitis. All patients had undergone at least one flexible sigmoidoscopy and 75 had a colonoscopy. Distal adenomas were found in three patients with ulcerative colitis compared with 67 of 749 controls (2.8% v 8.9%, chi(2) = 4.6, p = 0.03)., Conclusions: The results suggest that distal adenomatous polyps are rare in patients aged 55-64 years with IBD compared with a control population. This supports the hypothesis that lesions other than polyps are important for the development of colorectal cancer in patients with IBD.

Gastro-oesophageal reflux disease is a common medical problem caused by the exposure of the distal oesophagus to gastric contents. Existing medical therapy is very effective, but symptomatic relief with acid suppressants is often delayed. Treatment focuses on the suppression of gastric acid rather than on the underlying pathophysiological abnormalities, such as transient non-swallow-related lower oesophageal sphincter relaxation. Current pharmacological developments concentrate on drugs with lasting acid suppression and a faster onset of action. Compounds interacting with the complex neuromuscular regulation of the gastro-oesophageal junction are also being developed and offer exciting prospects.

The combination of ulcerative colitis, sclerosing cholangitis and coeliac disease is unusual. The two cases described here illustrate that the investigation and management of such patients can be difficult. Other diagnoses should be considered when a patient with a known pathology fails to respond to treatment. Review of the literature suggests an increased malignant potential in these patients. We conclude that patients with a combination of ulcerative colitis, sclerosing cholangitis and coeliac disease should undergo annual colonoscopic surveillance. In those with clinical deterioration and weight loss, early liver and bowel imaging should be carried out.

Over the last two decades there have been major advances in the medical treatment of gastro-oesophageal reflux disease (GORD) and Barrett's oesophagus. Motility agents, H(2)-receptor antagonists and proton-pump inhibitors (PPI) have all been evaluated in short- and long-term studies. Symptomatic response needs to be differentiated from healing of oesophagitis and maintenance of remission. Clinical trials have convincingly demonstrated the superiority of PPIs to motility agents and H(2)-receptor antagonists for all clinical aspects of GORD. Barrett's oesophagus requires lifelong acid suppression. Treatment with standard doses of PPIs is often insufficient and higher doses are frequently required. Medical treatment does not appear to result in clinically significant regression of Barrett's oesophagus.

Kikuchi's disease is usually a self limiting illness characterised by pyrexia, neutropenia, and cervical lymphadenopathy particularly in young women of Asian descent. This often leads to an initial misdiagnosis of lymphoma. A case of a young Asian woman who presented with pyrexia of unknown origin is described.