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Background: The response rate of hepatitis B virus (HBV) vaccination in patients with inflammatory bowel disease (IBD) is variable. Increasing dose or accelerated schedule is the suggested strategy to improve seroconversion., Aim: We performed a meta-analysis to determine the pooled response rate of HBV vaccination and to identify the predictors of seroconversion., Methods: We searched PubMed, Embase and Cochrane library databases. Studies reporting the response of HBV vaccination in IBD patients were included. Response was recorded as adequate immune response (AIR, >10 IU/L) and Effective immune response (EIR, >100 IU/L). Pooled AIR and EIR rates were calculated for different doses (10-20 μg or 40 μg) and schedules (standard: 0, 1 and 6 months or accelerated: 0, 1 and 2 months). Meta-analysis was performed to identify the predictors of response., Results: Twenty-one studies including 2602 patients were eligible. Pooled AIR and EIR rates after HBV vaccination were 62% (95% CI, 55-68) and 42% (95% CI, 37-48), respectively. Pooled AIR and EIR rates for standard and double dose were similar. Pooled AIR and EIR rates were also comparable for different schedules of HBV vaccination. Gender, IBD subtype and disease activity did not affect the response rate. Use of immunosuppression [immunomodulators (RR: 0.73, 95% CI, 0.62-0.87) and anti-TNFs (RR: 0.72, 95% CI, 0.60-0.87)] was a predictor of poor immune response compared to no immunosuppressive therapy., Conclusion: Patients with IBD have a poor serological response after HBV vaccination. HBV screening and vaccination should preferably be done before starting the immunosuppressive drugs., (© 2022 John Wiley & Sons Ltd.)

The introduction of new therapeutic agents in chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL), including the new kinase inhibitor idelalisib, has changed the therapeutic landscape of these diseases. However, the use of idelalisib is associated with a peculiar profile of side effects, which require an optimization of the current approach to prophylaxis and supportive treatment. Moving from the recognition that the abovementioned issue represents an unmet need in CLL and FL, a multidisciplinary panel of experts was convened to produce a consensus document aiming to provide practical recommendations for the management of the side effects during idelalisib therapy for CLL and FL. The present publication represents a consensus document from a series of meetings held during 2017. The Panel generated clinical key questions using the criterion of clinical relevance through a Delphi process and explored 4 domains, ie, diarrhea/colitis, transaminitis, pneumonitis, and infectious complications. Using the consensus method, the Panel was able to shape recommendations which may assist hematologist to minimize adverse events and guarantee adherence to treatment in patients with CLL and FL candidate to receive idelalisib. [ABSTRACT FROM AUTHOR]

The article presents abstracts on medical topics which include diagnosis of collagenous colitis, ulcer of remnant stomach and foreign bodies in upper gastrointestinal tract.

Ulcerative colitis (UC) is a chronic non‐specific inflammatory disease of the intestines with a high prevalence. Polymer‐prepared nanoparticles are well‐targeted, highly biocompatible, and have high potential for personalized therapy. Polymer nanoparticles are able to achieve localized therapy through their unique design. First, this review compares the advantages and disadvantages of natural and synthetic polymeric materials as well as describes the application of polymeric nanoparticles in UC therapy. Then, the preparation, characterization methods, and current challenges of common polymer nanoparticles are presented. Next, one‐by‐one examples of polymer nanoparticle‐targeted drug delivery strategies for the treatment of UC are presented. In addition, polymer nanoparticle‐based therapeutic approaches for UC, including anti‐inflammatory therapies, reactive oxygen species scavenging therapies, and intestinal flora modulation therapies, are presented. Finally, future research directions for polymer nanoparticles in UC therapy are discussed and current challenges are identified. The aim of this paper is to provide valuable references and guidance for researchers to design and develop novel UC therapies. [ABSTRACT FROM AUTHOR]

Background: This study aims to review and summarize the current up to date literature that explore the current treatment approaches to immune mediated colitis and the role of surgical specialties in the landscape of management. Methods: A narrative review of papers was performed following a literature search through Medline, EMBASE and Cochrane Central databases pertaining to immune mediated colitis as an adverse event of cancer immunotherapy. Results: Current guidelines for the diagnosis and treatment of immune mediated colitis mirror the approach to the workup of inflammatory bowel disease and guided by treating oncology and gastroenterology specialties. Immune mediated colitis however relies on surgical specific skills as a consequence of obtaining a diagnosis as well as in the management of complications that may arise. Conclusion: Immune mediate colitis management has largely been under the purview of medical specialties. This review explores the current landscape of managing immune mediated colitis from a surgical perspective and highlights key areas in which surgeons can engage in the multidisciplinary care of this condition. To facilitate prompt diagnosis and management of immune‐mediated colitis, there is an increasing necessity for surgeons to become familiar with the latest multidisciplinary approaches and recommendations. [ABSTRACT FROM AUTHOR]

There are currently no guidelines on the long-term management of patients after an episode of acute ischaemic colitis. Our aim was to review the literature on the pattern of presentation and the pathophysiology of this condition and to understand the current status of the acute and long-term management of ischaemic colitis. Furthermore, we aim to provide recommendations for the clinicians in regard to the acute and long-term management of ischaemic colitis. A review of the English literature over the last 15 years was performed using Embase and Medline. Search terms were ischaemic OR ischemic, colitis OR colon. Two reviewers screened the papers against pre-determined eligibility criteria. A senior consultant surgeon performed a final overview. Three hundred sixty-eight papers were identified on the initial search; 318 were irrelevant and 17 were conference abstracts; both were excluded. Thirty-three full articles were assessed for suitability; nine were further excluded. Twenty-four articles were included in the final analysis and cross-referenced against those listed in the systematic reviews. There is a large clinical heterogeneity in inclusion criteria (histological, radiological, endoscopic, surgical specimen). Twelve out of 24 articles included patients only based on histological diagnosis. The definition of right and left (or nonright) ischaemic colitis was variable based on whether hepatic or splenic flexure was used as the cut-off point. Five retrospective case series highlighted that patients with isolated right-sided ischaemic colitis had a worse prognosis than those with left-sided colitis (higher mortality, need for surgery, length of hospital stay). The overall recurrence was 9%. There is a need for a higher-level evidence to guide clinicians on the long-term management of patients following an episode of acute colonic ischaemia. Further evidence is required to determine whether right colonic ischaemia should be managed differently from left. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Kang et al papers. To view these articles, visit https://doi.org/10.1111/apt.17473 and https://doi.org/10.1111/apt.17501 [ABSTRACT FROM AUTHOR]

In a previous paper, the stereographic reconstruction of the crypt structure of ulcerative colitis using the RATOCK System was described. The relationship between the blood vessels and the crypt structure is the focus of the current paper, using two kinds of tissue staining color in which the color differs. Stereographic images make the relationship between the crypt structure and blood vessel distribution understandable at a glance. The methods used here are identical to those described in a previous paper. In the present paper, five cases of ulcerative colitis (UC) are examined. Biopsy specimens were obtained from the diseased, normal, and transitional zones (the area between the normal and diseased zones) from each patient. Three-dimensional reconstruction was created using TRI for Windows (RATOC System Tokyo, Japan) software. In the present paper, two kinds of dyeing method between H&E and monoclonal antibody staining of the tissue was used. It was proven that the distribution of gland and blood vessel is very clear in the 3-D reconstruction shown. (i) The blood vessels in the normal zones run parallel to the crypt in a regular manner and are almost identical to one another in diameter. (ii) In the transitional and diseased zones, the blood vessels show no clear direction and produce many branches without any apparent order. The blood vessels are, moreover, irregular in diameter. (iii) In short, clear parallelism is lost in both the transitional and diseased zones. Stereographic reconstruction of endoscopically obtained biopsy specimens of UC-affected tissues makes it possible to understand at a glance the distribution of blood vessels and their relationship to crypts. The relationship of these was clarified by the combined use of two kinds of dyeing method with three-dimensional reconstruction. [ABSTRACT FROM AUTHOR]

Correction to Epac-2 ameliorates spontaneous colitis in Il-10-/- mice by protecting the intestinal barrier and suppressing NF- B/MAPK signalling Epac-2 ameliorates spontaneous colitis in Il-10-/- mice by protecting the intestinal barrier and suppressing NF- B/MAPK signalling. In Song X et al.,[1] the -actin band in Figure 3F; the p65 band, p38 band and -actin band of Caco-2 cells in Figure 6A; the p65 band, p38 band and -actin band of RAW 264.7 cells in Figure 6E; and the p65 band, p38 band and -actin band of mice in Figure 6I have been reused multiple times. [Extracted from the article]

Radiation colitis is one of the most common complications in patients undergoing pelvic radiotherapy and there is no effective treatment in the clinic. Therefore, searching for effective agents for the treatment of radiation colitis is urgently needed. Herein, it is found that the essential element selenium (Se) is protective against radiation colitis through inhibiting X‐ray‐induced apoptosis, cell cycle arrest, and inflammation with the involvement of balancing the generation of reactive oxygen species after the irradiation. Mechanistically, Se, especially for selenium nanoparticles (SeNPs), induced selenoprotein expression and then functioned to effectively restrain DNA damage response, which reduced X‐ray‐induced intestinal injury. Additionally, SeNPs treatment also restrained the cyclic GMP‐AMP synthas (cGAS)‐ stimulator of interferon genes (STING)‐TBK1‐IRF3 signaling pathway cascade, thereby blocking the transcription of inflammatory cytokine gene, IL‐6 and TNF‐α, and thus alleviating inflammation. Moreover, inducing selenoprotein expression, such as GPX4, with SeNPs in vivo can regulate intestinal microenvironment immunity and gut microbiota to attenuate radiation‐induced colitis by inhibiting oxidative stress and maintaining microenvironment immunity homeostasis. Together, these results unravel a previously unidentified modulation role that SeNPs restrained radiation colitis with the involvement of inducing selenoprotein expression but suppressing cGAS‐STING‐TBK1‐IRF3 cascade. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Kang et al. papers. To view these articles, visit https://doi.org/10.1111/apt.17473 and https://doi.org/10.1111/apt.17518 [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Carbonnel et al paper. To view this article, visit https://doi.org/10.1111/apt.17352 [ABSTRACT FROM AUTHOR]

Background: Immunosuppressive molecules such as cytotoxic T lymphocyte‐associated antigen 4 (CTLA‐4), programmed cell death protein (PD‐1) and its ligand (PD‐L1) are markedly overexpressed in the tumour microenvironment, providing a means for immune escape. Targeting these molecules, novel immunotherapies manipulate the host immune system to better detect and kill cancer cells. This paper describes a case of drug‐induced autoimmune colitis and type 1 diabetes mellitus (T1DM) attributed to pembrolizumab. Clinical details: A 70‐year‐old male presented with a 1‐week history of diarrhoea, vomiting, mucositis and loss of appetite following his third treatment with pembrolizumab infusion for metastatic melanoma. The patient's pathology results and clinical symptoms were consistent with a diagnosis of colitis and diabetic ketoacidosis (DKA). Outcomes: The patient's symptoms resolved with interventions from the intensive care unit (ICU), endocrinology and gastroenterology teams. Due to the severity of the adverse drug reaction, pembrolizumab was ceased. The patient was discharged from the hospital with insulin for his T1DM and a 1‐month course of weaning prednisolone for his colitis. Conclusion: The potential for autoimmune side effects associated with pembrolizumab may not be fully recognised by all clinicians. This case report highlights the potential for serious adverse events and serves to demonstrate the requirement for clinicians to develop a routine approach for early identification and management of these events. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Olsen et al and Lucendo papers. To view these articles, visit https://doi.org/10.1111/apt.16381 and https://doi.org/10.1111/apt.16403 [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Bergman et al papers. To view these articles, visit https://doi.org/10.1111/apt.17708 and https://doi.org/10.1111/apt.18010. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Bergman et al. papers. To view these articles, visit https://doi.org/10.1111/apt.17708 and https://doi.org/10.1111/apt.18018. [ABSTRACT FROM AUTHOR]

The article discusses several papers related to colorectal disease. It states that the study from Oxford, England showed the increased risk of gastrointestinal cancer after cholecystectomy. It mentions report from the University if Southern California regarding the use of infliximab-induced ACNA vasculitis for patients with Crohn's colitis. It also relates the study on the use of colonoscopy imaging device in surgical endoscopy.

LINKED CONTENT: This article is linked to Dahl et al papers. To view these articles, visit https://doi.org/10.1111/apt.17201 and https://doi.org/10.1111/apt.17237 [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Dahl et al papers. To view these articles, visit https://doi.org/10.1111/apt.17201 and https://doi.org/10.1111/apt.17250 [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Zylberberg et al paper. To view this article, visit https://doi.org/10.1111/apt.16363 [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease is characterized by a chronic inflammatory state and is therefore associated with abnormalities in coagulation and a hypercoagulable state. Cerebral venous sinus thrombosis is a rare complication of inflammatory bowel disease yet contributes significant morbidity and mortality to those affected. Early diagnosis is critical, as a delay in diagnosis portends a worse prognosis. This paper seeks to highlight the increased risk of venous sinus thrombosis in patients with inflammatory bowel disease. We start by discussing the case of a seventeen-year-old female who presented with ulcerative colitis flare and developed new-onset seizures, found to be caused by a large venous sinus thrombosis. [ABSTRACT FROM AUTHOR]

The association of hormonal contraception with increased risk of inflammatory bowel disease (IBD) observed in females suggests involvement of ovarian hormones, such as estradiol, and the estrogen receptors in the progression of intestinal inflammation. Here, we investigated the effects of prophylactic SERM2 and estradiol supplementation in dextran sulfate sodium‐induced colitis using mice with intact ovaries and ovariectomized (OVX) female mice. We found that graded colitis score was threefold reduced in the OVX mice, compared to mice with intact ovaries. Estradiol supplementation, however, aggravated the colitis in OVX mice, increasing the colitis score to a similar level than what was observed in the intact mice. Further, we observed that immune infiltration and gene expression of inflammatory interleukins Il1b, Il6, and Il17a were up to 200‐fold increased in estradiol supplemented OVX colitis mice, while a mild but consistent decrease was observed by SERM2 treatment in intact animals. Additionally, cyclo‐oxygenase 2 induction was increased in the colon of colitis mice, in correlation with increased serum estradiol levels. Measured antagonist properties of SERM2, together with the other results presented here, indicates an exaggerating role of ERα signaling in colitis. Our results contribute to the knowledge of ovarian hormone effects in colitis and encourage further research on the potential use of ER antagonists in the colon, in order to alleviate inflammation. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a chronic disorder characterized by recurrent gastrointestinal inflammation, lacking a precise aetiology and definitive cure. The gut microbiome is vital in preventing and treating IBD due to its various physiological functions. In the interplay between the gut microbiome and human health, extracellular vesicles secreted by gut bacteria (BEVs) are key mediators. Herein, we explore the role of Roseburia intestinalis (R)‐derived EVs (R‐EVs) as potent anti‐inflammatory mediators in treating dextran sulfate sodium‐induced colitis. R was selected as an optimal BEV producer for IBD treatment through ANCOM analysis. R‐EVs with a 76 nm diameter were isolated from R using a tangential flow filtration system. Orally administered R‐EVs effectively accumulated in inflamed colonic tissues and increased the abundance of Bifidobacterium on microbial changes, inhibiting colonic inflammation and prompting intestinal recovery. Due to the presence of Ile‐Pro‐Ile in the vesicular structure, R‐EVs reduced the DPP4 activity in inflamed colonic tissue and increased the active GLP‐1, thereby downregulating the NFκB and STAT3 via the PI3K pathway. Our results shed light on the impact of BEVs on intestinal recovery and gut microbiome alteration in treating IBD. [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Sebastian et al and Li Wai Suen et al papers. To view these articles, visit https://doi.org/10.1111/apt.15456 and https://doi.org/10.1111/apt.15630. [ABSTRACT FROM AUTHOR]

Disrupted gastrointestinal (GI) motility is highly prevalent in patients with inflammatory bowel disease (IBD), but its potential causative role remains unknown. Herein, the role and the mechanism of impaired GI motility in colitis pathogenesis are investigated. Increased colonic mucosal inflammation is found in patients with chronic constipation (CC). Mice with GI dysmotility induced by genetic mutation or chemical insult exhibit increased susceptibility to colitis, dependent on the gut microbiota. GI dysmotility markedly decreases the abundance of Lactobacillus animlalis and increases the abundance of Akkermansia muciniphila. The reduction in L. animlalis, leads to the accumulation of linoleic acid due to compromised conversion to conjugated linoleic acid. The accumulation of linoleic acid inhibits Treg cell differentiation and increases colitis susceptibility via inducing macrophage infiltration and proinflammatory cytokine expression in macrophage. Lactobacillus and A. muciniphila abnormalities are also observed in CC and IBD patients, and mice receiving fecal microbiota from CC patients displayed an increased susceptibility to colitis. These findings suggest that GI dysmotility predisposes host to colitis development by modulating the composition of microbiota and facilitating linoleic acid accumulation. Targeted modulation of microbiota and linoleic acid metabolism may be promising to protect patients with motility disorder from intestinal inflammation. [ABSTRACT FROM AUTHOR]

Background Microscopic colitis (MC) is an underdiagnosed inflammatory bowel disease. Aim To develop an evidence-based clinical practice guide on MC current concepts. Methods Literature search was done on the Cochrane Library, EMBASE and MEDLINE electronic databases, which were consulted covering the period up until March 2015. Work groups were selected for each of the reviewed topics, with the purpose of drafting the initial statements and recommendations. They subsequently underwent a voting process based on the Delphi method. Each statement/recommendation was accompanied by the result of the vote the level of evidence, and discussion of the corresponding evidence. The grade of recommendation (GR) using the GRADE approach was established for diagnosis and treatment recommendations. Results Some key statements and recommendations are: advancing age increases the risk of developing MC, mainly in females. The symptoms of MC and IBS-D may be similar. If MC is suspected, colonoscopy taking biopsies is mandatory. Treatment with oral budesonide is recommended to induce clinical remission in patients with MC. Oral mesalazine is not recommended in patients with collagenous colitis for the induction of clinical remission. The use of anti-TNF-alpha drugs (infliximab, adalimumab) is recommended for the induction of remission in severe cases of MC that fail to respond to corticosteroids or immunomodulators, as an alternative to colectomy. Conclusions This is the first consensus paper on MC based on GRADE methodology. This initiative may help physicians involved in care of these patients in taking decisions based on evidence. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Wildt et al paper. To view this article, visit https://doi.org/10.1111/apt.16614 [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Zylberberg et al paper. To view this article, visit https://doi.org/10.1111/apt.16363 [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Meserve et al paper. To view this article, visit https://doi.org/10.1111/apt.16217 [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Olsen et al and papers. To view these articles, visit https://doi.org/10.1111/apt.16381 and https://doi.org/10.1111/apt.16409 [ABSTRACT FROM AUTHOR]

The integrity of the intestinal mucosal barrier is crucial for protecting the intestinal epithelium against invasion by commensal bacteria and pathogens, thereby combating colitis. The investigation revealed that the absence of TSP50 compromised the integrity of the intestinal mucosal barrier in murine subjects. This disruption facilitated direct contact between intestinal bacteria and the intestinal epithelium, thereby increasing susceptibility to colitis. Mechanistic analysis indicated that TSP50 deficiency in intestinal stem cells (ISCs) triggered aberrant activation of the TGF‐β signaling pathway and impeded the differentiation of goblet cells in mice, leading to impairment of mucosal permeability. By inhibiting the TGF‐β pathway, the functionality of the intestinal mucosal barrier is successfully restored and mitigated colitis in TSP50‐deficient mice. In conclusion, TSP50 played a crucial role in maintaining the intestinal mucosal barrier function and exhibited the preventive effect against the development of colitis by regulating the TGF‐β signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel diseases (IBDs) pose significant challenges in terms of treatment non‐response, necessitating the development of novel therapeutic approaches. Although biological medicines that target TNF‐α (tumour necrosis factor‐α) have shown clinical success in some IBD patients, a substantial proportion still fails to respond. Methods: We designed bispecific nanobodies (BsNbs) with the ability to simultaneously target human macrophage‐expressed membrane TNF‐α (hmTNF‐α) and IL‐23. Additionally, we fused the constant region of human IgG1 Fc (hIgG1 Fc) to BsNb to create BsNb‐Fc. Our study encompassed in vitro and in vivo characterization of BsNb and BsNb‐Fc. Results: BsNb‐Fc exhibited an improved serum half‐life, targeting capability and effector function than BsNb. It's demonstrated that BsNb‐Fc exhibited superior anti‐inflammatory effects compared to the anti‐TNF‐α mAb (infliximab, IFX) combined with anti‐IL‐12/IL‐23p40 mAb (ustekinumab, UST) by Transwell co‐culture assays. Notably, in murine models of acute colitis brought on by 2,4,6‐trinitrobenzene sulfonic acid（TNBS) and dextran sulphate sodium (DSS), BsNb‐Fc effectively alleviated colitis severity. Additionally, BsNb‐Fc outperformed the IFX&UST combination in TNBS‐induced colitis, significantly reducing colon inflammation in mice with colitis produced by TNBS and DSS. Conclusion: These findings highlight an enhanced efficacy and improved biostability of BsNb‐Fc, suggesting its potential as a promising therapeutic option for IBD patients with insufficient response to TNF‐α inhibition. Key points: A bispecific nanobody (BsNb) was created to target TNF‐α and IL‐23p19, exhibiting high affinity and remarkable stability.BsNb‐Fc inhibited the release of cytokines in CD4+T cells during co‐culture experiments.BsNb‐Fc effectively alleviated colitis severity in mouse model with acute colitis induced by DSS or TNBS, outperforming the IFX&UST combination. [ABSTRACT FROM AUTHOR]

Background: Crohn's disease is associated with small bowel cancer whilst risk of colorectal cancer is less clear., Aim: To ascertain the combined estimates of relative risk of these cancers in Crohn's disease., Methods: MEDLINE was searched to identify relevant papers. Exploding references identified additional publications. When two papers reviewed the same cohort, the later study was used., Results: Meta-analysis showed overall colorectal cancer relative risk in Crohn's disease as 2.5 (1.3-4.7), 4.5 (1.3-14.9) for patients with colonic disease and 1.1 (0.8-1.5) in ileal disease. Meta-regression showed reduction in relative risk over the past 30 years. Subgroup analysis showed Scandinavia had significantly lower colorectal cancer relative risk than the UK and North America. Cumulative risk analysis showed 10 years following diagnosis of Crohn's disease relative risk of colorectal cancer is 2.9% (1.5%-5.3%). Meta-analysis showed small bowel cancer relative risk in Crohn's disease is 33.2 (15.9-60.9). Small bowel cancer relative risk has not significantly reduced over the last 30 years., Conclusion: Relative risk of colorectal and small bowel cancers are significantly raised in Crohn's disease. Cumulative risk of colorectal cancer of 2.9% at 10 years suggests a potential benefit from routine screening. However, the value of screening requires rigorous appraisal.

LINKED CONTENT This article is linked to Pai et al and Buckle & Christensen papers. To view these articles, visit https://doi.org/10.1111/apt.16142 and https://doi.org/10.1111/apt.16203 [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Pai et al papers. To view these articles, visit https://doi.org/10.1111/apt.16142 and https://doi.org/10.1111/apt.16245 [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Wright et al and Samaan et al papers. To view these articles, visit https://doi.org/10.1111/apt.15263 and https://doi.org/10.1111/apt.15393. [ABSTRACT FROM AUTHOR]

In this paper, we identify mechanisms of watery diarrhea in microscopic colitis (MC). Biopsies from the sigmoid colon of patients with collagenous colitis and treated lymphocytic colitis were analyzed in miniaturized Ussing chambers for electrogenic sodium transport and barrier function with one-path impedance spectroscopy. Cytometric bead arrays (CBA) served to analyze cytokine profiles. In active MC, electrogenic sodium transport was diminished and epithelial resistance decreased. CBA revealed a Th1 cytokine profile featuring increased IFN-γ, TNF-α, and IL-1β levels. After four weeks of steroid treatment with budesonide, electrogenic sodium transport recovered while epithelial barrier defects remained. Diarrhea in MC results at least in part from a combination of impaired electrogenic sodium transport and barrier defects. From a therapeutic perspective it can be postulated that the functional importance of loss of ions may be higher than that caused by barrier impairment. [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Reilev et al paper. To view this article, visit https://doi.org/10.1111/apt.15648. [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Sebastian et al and Sebastian and Myers papers. To view these articles, visit https://doi.org/10.1111/apt.15456 and https://doi.org/10.1111/apt.15647. [ABSTRACT FROM AUTHOR]

Aim The present meta-analysis aims to compare short-term and long-term outcomes in patients undergoing laparoscopic or open subtotal colectomy for benign and malignant disease. Methods A literature search of Medline, Ovid, Embase and Cochrane databases was performed to identify studies published between 1992 and 2005, comparing laparoscopic (LSC) and open (OSC) subtotal colectomy. A random effect meta-analytical technique was used and sensitivity analysis performed on studies published since the beginning of 2000, higher quality papers, those reporting on more than 40 patients, and those studies reporting on adult cases or acute colitis. Results A total of eight studies satisfied the criteria for inclusion. These included outcomes on 336 patients, 143 (42.6%) of whom had undergone laparoscopic resection, with an overall conversion rate to open surgery of 5% (range 0–11.8%). Operative time was significantly longer in the laparoscopic group by 86.2 min ( P < 0.001) and throughout subgroup analysis, although it was only in patients with acute colitis that this finding was without significant heterogeneity. Operative blood loss was less in the laparoscopic group by 57.5 millilitres in high quality and studies published since 2000, and 65.3 millilitres in those reporting on more than 40 patients. There was no significant difference in early or long-term complications between the groups. A statistically significant reduction in length of postoperative stay was observed in the laparoscopic groups by 2.9 days ( P < 0.001). Conclusion Laparoscopic subtotal colectomy was associated with longer operating times but a reduced length of stay compared to open surgery. Although short-term outcomes were equivalent in both groups, the suggested benefits in terms of reduced long-term obstructive complications were not supported by this meta-analysis. [ABSTRACT FROM AUTHOR]

A variety of medicines have been used for the treatment of inflammatory bowel disease. Antibacterial therapy has demonstrated promise by both improving symptoms and causing disease remission. The mechanism is unknown, but may be related to either eliminating a key pathogen, decreasing the number of bacterial secretory products or defective particles, a direct immunomodulating effect, or reducing secondary bacterial invasion. Historically, a large number of bacterial species have been suspected as being major contributors to the etiology of inflammatory bowel disease, including ulcerative colitis and Crohn's disease. Many trials of antibacterial agents have been carried out in inflammatory bowel disease. Recently, treatments have focused on Gram-negative anaerobes and mycobacteria. The present paper briefly reviews antimicrobial and antimycobacterial treatments in inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

Background: The renin‐angiotensin system (RAS) has been associated with inflammatory bowel disease (IBD), supporting translational relevance of RAS blockers. Comparability of study design/outcomes is fundamental for data analysis/discussion. Objectives: We aimed at evaluating the heterogeneity among protocols and outcomes to study the effect of angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers in IBD. Methods: This study was performed and reported in accordance with the Cochrane recommendations and PRISMA (PROSPERO‐CRD42022323853). Systematic searches were performed in PubMed, Scopus and Web of Science. Studies that met the inclusion criteria were selected. Quality assessment of the studies was done with the SYRCLES's risk of bias tools for animal studies. Results: Thirty‐five pre‐clinical studies and six clinical studies were included. Chemical induction of colitis was the most used model, but variable doses of the induction agent were reported. All studies reported at least a disease activity index, a macroscopic score, or a histologic assessment, but these scores were methodologically heterogeneous and reported for different characteristics. Great heterogeneity was also found in drug interventions. Inflammatory markers assessed as outcomes were different across studies. Conclusion: Lack of standardization of protocols and outcomes among studies threatens the evidence on how RAS blockers influence IBD outcomes. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a chronic gastrointestinal inflammatory disease associated with CD4+ Th1 and Th17 cell immune responses. Tumour necrosis factor‐associated factor 5 (TRAF5) deficiency has been shown to aggravate DSS‐induced colitis. However, the potential role of TRAF5 in regulating CD4+ T cell immune responses in the pathogenesis of IBD remains unclear. TRAF5−/− CD4+CD45RBhigh T cells and WT CD4+CD45RBhigh T cells were transferred to Rag2−/− mice via intravenous (i.v.) tail injection, respectively, to establish a chronic colitis model. Adeno‐associated virus (AAV)‐mediated gene knockout technique was used to knock out runt‐associated transcription factor 1 (Runx1) expression in vivo. Specific cytokines of Th1 and Th17 cells were detected by quantitative RT‐PCR, immunohistochemistry, ELISA, and flow cytometry. In T‐cell transfer colitis mice, the Rag2−/− mice reconstituted with TRAF5−/− CD4+CD45RBhigh T cells showed more severe intestinal inflammation than the WT control group, which was characterised by increased expression of INF‐γ, TNF‐α, IL‐17a. Furthermore, we found that the INF‐γ+CD4+, IL17a+CD4+, and INF‐γ+ IL17a+CD4+ T cells in the intestinal mucosa of Rag2−/− mice reconstituted with TRAF5−/− CD4+CD45RBhigh T cells were significantly higher than those of the WT control group by flow cytometry. Mechanistically, knockout Runx1 inhibited the differentiation of TRAF5−/− CD4+ T cells into Th1 and Th17 cells in the intestinal mucosa of T‐cell transfer colitis mice. TRAF5 regulates Th1 and Th17 cell differentiation and immune response through Runx1 to participate in the pathogenesis of colitis. Thus targeting TRAF5 in CD4+ T cells may be a novel treatment for IBD. [ABSTRACT FROM AUTHOR]

Bacterial extracellular vesicles (BEVs) are nano‐size particles secreted by bacteria that carry various bioactive components. These vesicles are thought to provide a new window into the mechanisms by which bacteria affect their hosts, but their fundamental proprieties within human remain poorly understood. Here, we developed a single‐vesicle analytical platform that enabled BEV detection in complex biological samples of host. Using this platform, we found the presence of BEVs in the host circulation and they were mainly derived from gut microbes. We showed that the levels of circulating BEVs in humans significantly increased with aging due to an age‐related increase in intestinal permeability. Significantly different levels of BEVs in blood were also found in patients with colorectal cancer and colitis. Together, our study provides new insights into circulating BEV biology and reveals their potential as a new class of biomarkers. [ABSTRACT FROM AUTHOR]

Background and Aim: Autophagy and gut microbiota correlates closely with the inflammatory bowel disease. Herein, we aimed to study the roles of rapamycin on the gut microbiota in inflammatory bowel disease. Methods: Acute colitis was induced with dextran sodium sulfate (DSS) and 2,4,6‐trinitrobenzenesulfonic acid solution in mice. Mice were administered with rapamycin or hydroxychloroquine. Weight loss, disease activity index scores, histopathological score, serum inflammatory cytokines, intestinal permeability, and colonic autophagy‐related proteins were detected. Cecal content was also preserved in liquid nitrogen and subsequently analyzed following the 16S DNA sequencing. The antibiotic cocktail‐induced microbiome depletion was performed to further investigate the relationship between autophagy activation and gut microbiota. Results: Compared with the control group, the colonic autophagy‐related proteins of P62, mTOR, and p‐mTOR increased significantly, while the levels of LC3B and ATG16L1 decreased (all P < 0.05) in the model group. After rapamycin intervention, the colonic pathology of mice improved, while the disease activity index score decreased substantially; the colon length increased, and the expression of IL‐6 and TNF‐α decreased. Following hydroxychloroquine treatment, some indicators suggested aggravation of colitis. Principal coordinates analysis showed that the DSS group was located on a separate branch from the rapamycin group but was closer to the hydroxychloroquine group. Compared with the DSS group, the rapamycin group was associated with higher abundances of f_Lactobacillaceae (P = 0.0151), f_Deferribacteraceae (P = 0.0290), g_Lactobacillus (P = 0.0151), g_Mucispirillum (P = 0.0137), s_Lactobacillus_reuteri (P = 0.0028), and s_Clostridium sp Culture_Jar‐13 (P = 0.0082) and a lower abundance of s_Bacteroides_sartorii (P = 0.0180). Linear discriminant analysis effect size showed that rapamycin increased the abundances of Lactobacillus‐reuteri, Prevotellaceae, Paraprevotella, Christensenella and Streptococcus and decreased those of Peptostreptococcaceae and Romboutsia Bacteroides‐sartorii. Besides, the improvement effect of autophagy activation on colitis disappears following gut microbiome depletion. Conclusion: The therapeutic effects of rapamycin on extenuating experimental colitis may be related to the gut microbiota. [ABSTRACT FROM AUTHOR]

Summary: Background: Microscopic colitis (MC) has been linked to several autoimmune conditions. Results from previous studies on the association with rheumatoid arthritis (RA) have been inconsistent. Aim: To assess the risk of future RA in MC. Methods: We conducted a nationwide matched cohort study in Sweden of 8179 patients with biopsy‐verified MC (diagnosed in 2007–2017), 36,400 matched reference individuals and 8202 siblings without MC, with follow‐up until 2021. Information on MC was obtained from all of Sweden's regional pathology registers (n = 28) through the ESPRESSO cohort. Data on incident RA were collected from the National Patient Register. Using Cox regression, we calculated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). Results: During a median follow‐up of 9.1 years (interquartile range = 6.7–11.7), 73 MC patients and 183 reference individuals from the general population were diagnosed with RA (99 vs. 55 events per 100,000 person‐years), equivalent to one extra case of RA in 226 patients with MC followed for 10 years. These rates corresponded to an aHR of 1.83 (95% CI = 1.39–2.41). The aHR was highest during the first year of follow‐up (2.31 [95% CI = 1.08–4.97]) and remained significantly elevated up to 5 years after MC diagnosis (aHR 2.16; 95% CI = 1.42–3.30). Compared to siblings, without MC, the aHR was 2.04 (95% CI = 1.18–3.56). Conclusion: Patients with MC are at a nearly two‐fold risk of developing RA compared to the general population. Knowledge of this increased risk may expedite evaluation for RA in patients with MC presenting with joint symptoms and/or arthralgia, thus preventing delay until RA diagnosis. [ABSTRACT FROM AUTHOR]

Background: Ulcerative colitis, a typical subtype of inflammatory bowel disease, can cause many serious complications. Burdock fructooligosaccharide (BFO), a linear inulin with a purity of 99.439% and a molecular weight of 2345 Da, demonstrates anti‐inflammatory and immunomodulatory properties. Methods: The Kunming mice were divided into two experimental models: a normal pretreatment model and a colitis experimental model. During the experimental treatment period, we assessed changes in weight and disease activity index (DAI), quantified the intestinal index, and determined myeloperoxidase (MPO) activity and reactive oxide species (ROS) levels in colitis mice. We also photographed colon morphology to investigate alterations in the integrity of the intestinal barrier function. Finally, we performed ELISA and qRT‐PCR to evaluate the anti‐inflammatory effect of BFO treatment on colitis mice. Result: The long‐term oral administration of BFO alone exhibited protective effects by preventing disruption of the intestinal functional structure and increasing the colon index in mice. However, in a dextran sodium sulfate (DSS)‐induced colitis mouse model, BFO administration facilitated quick recovery of body weight and effectively reduced the DAI, especially in the BFO‐H group (500 mg/kg/day). BFO treatment maintained the integrity of the intestinal barrier by attenuating the crypt distortion and increasing the goblet cells count It restored the DSS‐induced colon shortening and reduced the symptoms of colitis. These effects may be attributed to the appropriate concentrations of BFO effectively inhibiting MPO activity, clearing excessive ROS, and relieving spleen abnormalitie. BFO also attenuated the overexpression and excessive secretion of inflammatory cytokines (TNF‐α, IL‐1β, IL‐6, and MCP‐1) induced by DSS, reduced intestinal inflammation, and consequently protected the intestinal barrier function. Conclusion: BFO effectively alleviated the symptoms of DSS‐induced colitis by mediating anti‐inflammatory effects and protecting the intestinal barrier integrity, thereby potentially facilitating the utilization of safer and more efficacious polysaccharides for managing chronic inflammatory diseases. [ABSTRACT FROM AUTHOR]

Intestinal epithelial cells are covered by the brush border, which consists of densely packed microvilli. The Intermicrovillar Adhesion Complex (IMAC) links the microvilli and is required for proper brush border organization. Whether microvillus crosslinking is involved in the intestinal barrier function or colitis is currently unknown. We investigate the role of microvillus crosslinking in colitis in mice with deletion of the IMAC component CDHR5. Electron microscopy shows pronounced brush border defects in CDHR5‐deficient mice. The defects result in severe mucosal damage after exposure to the colitis‐inducing agent DSS. DSS increases the permeability of the mucus layer and brings bacteria in direct contact with the disorganized brush border of CDHR5‐deficient mice. This correlates with bacterial invasion into the epithelial cell layer which precedes epithelial apoptosis and inflammation. Single‐cell RNA sequencing data of patients with ulcerative colitis reveals downregulation of CDHR5 in enterocytes of diseased areas. Our results provide experimental evidence that a combination of microvillus crosslinking defects with increased permeability of the mucus layer sensitizes to inflammatory bowel disease. Synopsis: Crosslinking of microvilli in the intestinal brush border mediated by CDHR5 represents an important barrier against invasion of luminal bacteria. A combination of reduced crosslinking with increased mucus layer permeability may sensitize to inflammatory bowel disease. Deletion of CDHR5 leads to microvilli shortening and brush border disorganization in the small and large intestine of mice.CDHR5 protects mice from DSS‐induced colitis, but not from hapten‐induced T cell‐mediated colitis.Microvilli crosslinking prevents entry when the mucus layer becomes permeable and bacteria reach intestinal epithelia.CDHR5 is downregulated in the inflamed epithelium compared to the non‐inflamed epithelium of ulcerative colitis patients. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Colitis cystica profunda (CCP) is a rare benign disease characterized by mucus‐filled cysts in the submucosa. Endoscopic, radiological and histological examinations are not highly specific, which can lead to misdiagnosis, resulting in unnecessary radical surgical resection. This report presents two cases of CCP with their clinical and imaging features. [ABSTRACT FROM AUTHOR]