Pharmacologic Management of Non-Eosinophilic Esophagitis Eosinophilic Gastrointestinal Diseases.

Data for pharmacologic treatments for non-eosinophilic esophagitis (EoE) eosinophilic gastrointestinal diseases (EGIDs) are limited. Nevertheless, because of the increasing understanding of EGID pathogenesis, a number of medications are used to treat EGIDs, though all are currently off-label. Initial therapy generally starts with corticosteroids, and "topical" delivery is preferred over systemic due to long-term side effects. A number of other small molecules could potentially be used, ranging from allergy medications to immunosuppressants. Biologics are also being used and investigated for EGIDs and represent promising targeted therapies. Multiple therapeutic targets have also been identified, many of which overlap with EoE targets.

Case report: Successful treatment of ulcerative colitis-related post-colectomy enteritis refractory to multiple therapies with ustekinumab.

Ulcerative colitis-related severe post-colectomy enteritis is a rare condition. A few cases have undergone successful treatment with corticosteroids, Cyclosporine, Azathioprine, and Infliximab. We aim to evaluate the treatment outcome of ustekinumab in this rare case. Here we describe a 56-year-old woman with post-colectomy enteritis refractory to multiple therapies. Finally, the patient was administered with ustekinumab treatment. Under monitoring, the feces volume of the patient decreased from 5000-7000 mL per day to 1700-2000 mL. Over a one-year follow-up period, the patient gradually gained body weight, with the stoma drainage of formed brown stool. And the villi of the small intestinal mucosa restore growth. To our knowledge, this is the first report that indicates ustekinumab could be a treatment selection for ulcerative colitis-related severe post-colectomy enteritis.

Enteritis: a window to the diagnosis of systemic lupus erythematosus in an adolescent girl: case report.

BACKGROUND: Enteritis is one of the rare systemic manifestations in childhood-onset systemic lupus erythematosus and its diagnosis is very challenging. This is a rare case of an adolescent girl with recurrent non-specific gastro-intestinal symptoms which were later diagnosed to be owing to lupus enteritis, the only presenting manifestation of an active flare. CASE REPORT: A 15-year-old girl was admitted with recurrent episodes of abdominal pain, vomiting and loose stools. She had diffuse abdominal tenderness. Abdominal ultrasonography demonstrated moderate ascites. A contrast-enhanced abdominal computerised tomography scan revealed thickening of the small bowel wall. On colonoscopy, there were rectal erosions, and microscopic examination of the biopsy specimens demonstrated mild inflammation. Non-specific enteritis was diagnosed and she was given antibiotics and supportive care. She was re-admitted 6months later with abdominal pain. An abdominal contrast-enhanced computerised tomography scan revealed thickening of the bowel wall and the target sign and comb sign in the small intestine. The anti-nuclear antibody was positive. Renal biopsy demonstrated grade 2 lupus nephritis. Lupus enteritis was diagnosed and the case satisfied the 2019 EULAR-ACR criteria and SLICC criteria. She was treated with methylprednisolone, cyclophosphamide and hydroxychloroquine. She improved with treatment and has remained asymptomatic during follow-up. CONCLUSION: This case emphasises the need for healthcare providers to be alert to the possibility of lupus enteritis. It also highlights the importance of close follow-up of cases who have non-specific gastro-intestinal symptoms. Lupus enteritis should be considered in the differential diagnosis of recurrent non-specific gastro-intestinal symptoms in children, especially adolescents, to ensure timely diagnosis and treatment.Abbreviations: ACR American College of Rheumatology; ANA anti-nuclear antibody; CRP: C-reactive protein; CT: computerised tomography; CECT: contrast-enhanced computerised tomography; EULAR: European League Against Rheumatism; GI: gastro-intestinal; LE: lupus enteritis; SLE systemic lupus erythematosis; SLICC: Systemic Lupus International Collaborating Clinics; SLEDAI: SLE disease activity index.

Racecadotril Versus Loperamide in Acute Radiation Enteritis: A Randomized, Double-Masked, Phase 3, Noninferiority Trial.

PURPOSE: There is currently no gold standard for the management of acute radiation enteritis. We compared the efficacy and safety of Racecadotril, an anti-hypersecretory drug, versus Loperamide, an anti-motility agent, in acute radiation enteritis. METHODS AND MATERIALS: We conducted a randomized, double-masked, non-inferiority trial at a single research institute. Patients receiving curative radiation for pelvic malignancies, who developed grade 2 or 3 diarrhea (as per Common Terminology Criteria for Adverse Events, v 4.0) were included in the study. Patients in the intervention arm received Racecadotril and placebo. Patients in the control arm received Loperamide and placebo. The primary outcome was the resolution of diarrhea, 48 hours after the start of treatment. RESULTS: 162 patients were randomized between 2019 and 2022. On intention-to-treat analysis, 68/81 patients, 84%, (95% CI, 74.1%-91.2%) in the Racecadotril arm and 70/81, 86.4%, (95% CI, 77.0%-93.0%) in the Loperamide arm improved from grade 2 or 3 diarrhea to grade 1 or 0, (P= .66, χ2 test). The difference in proportion was 2.4% (95% CI: -8.5% to 13.4%). Since the upper boundary of the 95% CI crossed our non-inferiority margin of 10% (13.4%) we could not prove the non-inferiority of Racecadotril over Loperamide. Rebound constipation was more in the Loperamide arm compared to Racecadotril (17.3% vs 6.2%; P = .028) CONCLUSIONS: The non-inferiority of Racecadotril to Loperamide in acute radiation enteritis could not be demonstrated. However, Racecadotril can be the preferred drug of choice in acute radiation enteritis because Racecadotril does not affect bowel motility, achieved a high clinical success rate similar to that of Loperamide, and was associated with lesser side effects.

[Analysis of short-term efficacy of perioperative fecal microbiota transplantation combined with nutritional support in patients with radiation-induced enteritis complicated by intestinal obstruction].

Objective: To explore the short-term efficacy of perioperative fecal microbiota transplantation combined with nutritional support in patients with radiation-induced enteritis complicated by intestinal obstruction. Methods: The cohort of this prospective cohort study comprised 45 patients (nine men and 36 women) with radiation-induced enteritis complicated by intestinal obstruction admitted to Shanghai Tenth People's Hospital Affiliated to Tongji University from January 2022 to October 2022. The median age was 53 (42-65) years. Thirty-five of the patients had gynecological tumors and 10 colorectal malignancies. The patients were randomly allocated to a fecal microbiota transplantation group of 20 patients who underwent fecal microbiota transplantation starting 2 weeks before surgery for 6 days, in addition to receiving conventional perioperative treatment, and a conventional treatment group of 25 patients who only received nutritional support during the perioperative period. There were no significant differences in baseline characteristics (sex, age, preoperative nutritional indices, and surgical procedure) between the two groups (all P>0.05). Postoperative recovery (time to passing flatus or a bowel movement, length of stay) and complications were compared between the two groups. Postoperative complications within 30 days after surgery classified in accordance with the international Clavien-Dindo classification of surgical complications (I-V) were statistically analyzed. Improvement in gastrointestinal symptoms, namely abdominal pain, distension, diarrhea, and rectal bleeding) and gastrointestinal quality of life scores (which include 36 problems rated 0-144 points related to physical, psychological, social activities and family life; the lower the score, the more severe the symptoms) were compared between the two groups. Nutritional recovery was assessed by body mass, body mass index, total protein, albumin, prealbumin, and hemoglobin. Results: Compared with the conventional treatment group, the postoperative hospital stay was shorter in the fecal microbiota transplantation group (8.0±4.3 days vs. 11.2±5.4 days, t=2.157, P=0.037) and the time to passage of flatus or having a bowel movement was earlier (2.2±3.2 days vs. 3.9±2.3 days, t=2.072, P=0.044). There were 26 postoperative complications in the fecal microbiota transplantation group and 59 in the conventional treatment group. There were 20 and 36 Grade I to II complications and no and three Grade III to V complications in the transplantation and conventional treatment group, respectively. The overall grade of complication did not differ significantly between the two groups (P=0.544). However, the incidence of postoperative intestinal inflammatory obstruction was lower in the fecal microbiota transplantation than the conventional treatment group (10.0% [2/20] vs. 40.0% [10/25], P=0.040). One patient in the conventional treatment group died. This patient had complete intestinal obstruction complicated by severe malnutrition preoperatively, and an intestinal fistula complicated by abdominal infection postoperatively, and died despite active treatment. Nineteen and 23 patients in the transplantation and conventional treatment group, respectively, attended for follow-up 1 month after surgery; 19 and 21, respectively, attended for follow-up 3 months after surgery, and 17 and 20, respectively, attended for follow-up 6 months after surgery. There were no significant differences between the two groups in abdominal pain or rectal bleeding 1, 3, or 6 months after surgery (all P>0.05). One month after surgery, the incidence of abdominal distension and diarrhea was lower in the fecal microbiota transplantation than in the conventional treatment group (3/19 vs. 48.0% [11/23], P=0.048; 3/19 vs. 52.2% [12/23], P=0.023). However, at the 3 and 6 month follow-ups the incidence of abdominal distension and diarrhea had gradually decreased in both groups and the differences between the groups were not statistically significant (P>0.05 for all). Scores for gastrointestinal quality of life improved significantly in both treatment groups compared with preoperative values (F=71.250, P<0.001; F=79.130, P<0.001, respectively). Scores for gastrointestinal quality of life were higher in the fecal microbiota transplantation than the conventional treatment group at all follow-up time points (P<0.05). One-way ANOVA showed that body mass, body mass index, and total protein, albumin and hemoglobin concentrations improved in both groups compared with preoperative values (all P<0.05). Prealbumin concentration improved significantly in the transplantation (F=5.514, P=0.002), but not in the conventional, group (F=1.535, P=0.211). The improvements in body mass, body mass index, total protein, and albumin were better in the fecal microbiota transplantation than conventional treatment group at 3 and 6 months of follow-up (all P<0.05). Conclusion: Perioperative fecal microbiota transplantation combined with nutritional support is effective in improving early postoperative nutritional status and quality of life in patients with radiation-induced enteritis complicated by intestinal obstruction.

Intraoperative appearance of radiation enteritis: What should be resected?

Radiation enteritis can appear up to 30 years after radiotherapy. Outside acute complications, it usually manifests itself as chronic intestinal obstruction. If medical treatment (corticosteroid therapy) fails, surgical treatment is indicated, namely resection of the affected bowel, with removal of the ileo-caecal valve.

Non-esophageal eosinophilic gastrointestinal diseases: a narrative review.

Eosinophilic gastrointestinal disorders are a group of rare diseases characterized by the infiltration of eosinophils in the gastrointestinal wall in a greater amount than in homeostatic conditions. 'Non-esophageal eosinophilic gastrointestinal disorders' is the umbrella term for all eosinophilic gastrointestinal disorders outside of the well known eosinophilic esophagitis. This includes eosinophilic gastritis, eosinophilic enteritis and eosinophilic colitis. The clinical presentation is atypical and not very different for the three disorders. The depth of infiltration has a bigger influence on the presenting symptoms than the disease location. Although the frequency of diagnosis and research in this subject is increasing over time, non-esophageal eosinophilic disorders are rare and high quality evidence is limited to date. In this narrative review, we provide an overview of the latest insights in the pathophysiology, diagnostic approach and available treatment options. Transcriptome studies have found the pathogenesis to be T helper type 2 driven. Various laboratory findings can be used to trigger raised suspicion and investigation with endoscopy. As the endoscopic appearance of the mucosa is normal in most cases, multiple biopsies in each segment are needed to quantify the amount of eosinophils in the tissue. Eosinophilic cut-offs for diagnosis are a controversial topic and a consensus is still lacking. A recently developed tissue based diagnostic platform which measures differentially expressed genes might be available in the future to classify patients with intermediate eosinophilic tissue levels under the cut-off. For the treatment, corticosteroids are still the cornerstone of treatment but promising research suggests a role of biologicals, such as Lirentelimab (anti-siglec 8) in particular.

Dosimetry and acute radiation enteritis comparison between prone and supine position in IMRT for gynecological cancers.

PURPOSE: To probe the differences of dosimetry and acute radiation enteritis between prone and supine position in gynecological cancer patients treated with intensity-modulate radiotherapy (IMRT). METHODS: Gynecologic tumor patients who received IMRT from January 2020 to July 2021 were analyzed. 60 patients were enrolled and divided into the supine or prone position group according to different radiotherapy positions, including 34 patients in prone position and 26 patients in supine position. The dose-volume histogram of organs at risk (OARs) and the incidence of acute radiation enteritis were compared between the two groups. Multivariate logistic regression analysis was conducted to show the clinical characteristics and dose volume metrics to the association of acute radiation enteritis. RESULTS: The percentage of volume receiving 5 Gy, 10 Gy, 15 Gy, 20 Gy, 30 Gy, 40 Gy, and 45 Gy doses for the small intestine were 79.0%, 67.4%, 59.6%, 44.3%, 17.0%, 8.9%, and 6.0%, respectively in the prone group, which were lower than those in the supine group (P < 0.05). The mean radiation dose (Dmean ) of the small intestine exposure in prone group was decreased (P < 0.001). Compared with the supine group, the prone group who suffered from acute radiation enteritis were much less. The probability of indigestion, nausea, vomiting, diarrhea, and abdominal pain in the prone position were 35.29%, 29.41%, 17.65%, 38.24%, and 5.88%, respectively. The differences in indigestion, nausea, and diarrhea between the two groups were statistically significant (P = 0.012, P = 0.029, and P = 0.041). Multivariate logistic regression analysis was shown that prone position was found to be protective against indigestion (P = 0.002), nausea (P = 0.013), vomiting (P = 0.035), and abdominal pain (P = 0.021). CONCLUSION: Prone position in IMRT for gynecological cancers could significantly reduce radiation dose to the small bowel and colon, which would decrease the occurrence and severity of acute intestinal side effects possibly.

[Relationship between chronic radiation enteritis of cervical cancer and gut microbiota].

OBJECTIVE: To explore the relationship between gut microbiota and chronic radiation enteritis of cervical cancer patients. METHODS: Fecal samples were collected from 34 patients with cervical cancer who had received radiotherapy for at least 6 months but less than 2 years. The patients were divi-ded into mild toxicity group (mild, M) with no symptoms or mild symptoms and severe toxicity group (severe, S) with severe symptoms by clinical diagnosis of radiation enteritis, modified inflammatory bo-wel disease questionnaire (IBDQ) and Vaizey questionnaire. DNA extracted from fecal samples was sequenced and analyzed by 16S rRNA sequencing method. The analysis indexes included α-diversity, ß-diversity, taxonomic composition analysis, taxonomic hierarchy tree and linear discriminant analysis (LDA) effect size (LEfSe). RESULTS: From the perspective of species diversity, most indices of α diversity in group M were higher than those in group S. Although there was no significant difference, it also indicated a correlation between low species diversity and severity of intestinal symptoms to some extent. There was also a significant difference in the distribution of ß diversity between the two groups, indicating that the microbial characteristics were different between the two groups. From the perspective of species composition, the M group had higher Firmicutes [66.5% (M) vs. 56.0% (S)] and lower Proteobacteria [4.1% (M) vs. 13.9% (S)] than the S group at the level of phyla. At the level of genus, there were also significant differences between the two groups: Shigella [2.7% (M) vs. 8.5% (S)], Faeca-libacterium [7.0% (M) vs. 2.7% (S)], Lachnospiraceae_Clostridium [1.3% (M) vs. 4.7% (S)]. Through LEfSe also found some species with statistically significant differences between the two groups. The abundance of Peptoniphilus, Azospirillum and Actinomyces in group M was significantly higher, while the abundance of Veillonellaceae, Rhodobacteraceae, and Rhodobacterales in group S was significantly higher. The taxonomic hierarchy tree also intuitively showed the difference in species composition between the two groups at each taxonomic level in space. CONCLUSION: The severity of chronic radiation enteritis of cervical cancer is closely related to the characteristics and composition of gut microbiota.

Gut microbiota controlling radiation-induced enteritis and intestinal regeneration.

Cancer remains the second leading cause of mortality, with nearly 10 million deaths worldwide in 2020. In many cases, radiotherapy is used for its anticancer effects. However, radiation causes healthy tissue toxicity as a side effect. In intra-abdominal and pelvic malignancies, the healthy bowel is inevitably included in the radiation field, causing radiation-induced enteritis and dramatically affecting the gut microbiome. This condition is associated with significant morbidity and mortality that impairs cancer patients' and survivors' quality of life. This Review provides a critical overview of the main drivers in modulating the gut microenvironment in homeostasis, disease, and injury, focusing on gut microbial metabolites and microorganisms that influence epithelial regeneration upon radiation injury.

Successful treatment of refractory enteritis and arthritis with combination of tumour necrosis factor and interleukin-6 inhibition in patients with ulcerative colitis.

An 18 year-old man with autoimmune hepatitis-primary sclerosing cholangitis-overlap syndrome and ulcerative colitis was admitted due to relapsed enteritis and polyarthritis after cessation of infliximab. Colonoscopy and articular ultrasonography revealed large ulcers in the colon with crypt abscess in the specimens and active enthesitis and synovitis, respectively. His intestinitis was improved with golimumab but arthritis was persistent. Golimumab was switched to secukinumab, which was effective for arthritis. However, colitis was flared resulting in total colorectal resection. One month after colectomy, polyarthritis was relapsed. Tocilizumab ameliorated arthritis but enteritis emerged again, and switching tocilizumab to adalimumab improved enteritis but arthritis exacerbated. Finally, we restarted tocilizumab for arthritis with continued adalimumab for enteritis. The dual cytokine blocking strategy, tumour necrosis factor-α and interleukin-6 inhibition, subsided both of his refractory enteritis and arthritis and maintained remission for more than 3 years without any serious adverse event. Our case suggests that enteritis and arthritis in inflammatory bowel disease may be different in pathophysiology and raises the possible usefulness of simultaneous inhibition of two inflammatory cytokines in such cases.

Manifestaciones toracoabdominales de las enfermedades relacionadas con la inmunoglobulina G4 / Thoracoabdominal manifestations of immunoglobulin G4-related disease

Las enfermedades relacionadas con la IgG4 (ER-IgG4) son un conjunto de enfermedades inmunomediadas que, hasta no hace mucho tiempo, se consideraban como entidades individuales. Se ha demostrado la existencia de una clínica, una serología y una patogenia similares, por lo que, actualmente, se considera como una única enfermedad multisistémica. Su característica común es la infiltración de los tejidos afectados por células plasmáticas y linfocitos IgG4 positivos. Se han propuesto 3 criterios mayores para su diagnóstico, que son el clínico, el analítico y el anatomopatológico. El páncreas es el órgano que más se afecta en esta enfermedad, pudiendo simular un proceso tumoral. De ahí que se haya descrito una serie de signos que podrían hacernos sospechar que no se trata de una neoplasia (signo del halo, del conducto penetrante, ausencia de invasión vascular, etc.). El diagnóstico diferencial es importante de cara a evitar cirugías innecesarias (AU)

Immunoglobulin G4-related disease (IgG4-RD) comprises a group of immune-mediated diseases that, until recently, were considered separate entities. These entities have a similar clinical presentation, serological findings, and pathogenesis, so they are currently considered a single multisystemic disease. The common characteristic is the infiltration of involved tissues by plasma cells and lymphocytes that are positive for IgG4. Three major criteria have been proposed for the diagnosis of IgG4-RD: clinical, laboratory, and histological. The pancreas is the organ that is most affected by IgG4-RD, which can simulate a tumor. In this respect, a series of signs could help us suspect that the pancreatic findings do not reflect a tumor (halo sign, duct-penetrating sign, absence of vascular invasion, etc.). The differential diagnosis is important to avoid unnecessary surgical interventions (AU)

Establishment of a prediction model for severe acute radiation enteritis associated with cervical cancer radiotherapy.

BACKGROUND: Cervical cancer is one of the most common gynecological malignant tumors. Radiation enteritis (RE) leads to radiotherapy intolerance or termination of radiotherapy, which negatively impacts the therapeutic effect and seriously affects the quality of life of patients. If the incidence of RE in patients can be predicted in advance, and targeted clinical preventive treatment can be carried out, the side effects of radiotherapy in cervical cancer patients can be significantly reduced. Furthermore, accurate prediction of RE is essential for the selection of individualized radiation dose and the optimization of the radiotherapy plan. AIM: To analyze the relationships between severe acute RE (SARE) of cervical cancer radiotherapy and clinical factors and dose-volume parameters retrospectively. METHODS: We included 50 cervical cancer patients who received volumetric modulated arc therapy (VMAT) from September 2017 to June 2018 in the Department of Radiotherapy at The First Affiliated Hospital Soochow University. Clinical and dose-volume histogram factors of patients were collected. Logistic regression analysis was used to evaluate the predictive value of each factor for SARE. A nomogram to predict SARE was developed (SARE scoring system ≥ 3 points) based on the multiple regression coefficients; validity was verified by an internal verification method. RESULTS: Gastrointestinal and hematological toxicity of cervical cancer VMAT gradually increased with radiotherapy and reached the peak at the end of radiotherapy. The main adverse reactions were diarrhea, abdominal pain, colitis, anal swelling, and blood in the stool. There was no significant difference in the incidence of gastrointestinal toxicity between the radical and postoperative adjuvant radiotherapy groups (P > 0.05). There were significant differences in the small intestine V20, V30, V40, and rectal V40 between adjuvant radiotherapy and radical radiotherapy after surgery (P < 0.05). Univariate and multivariate analyses revealed anal bulge rating (OR: 14.779, 95%CI: 1.281-170.547, P = 0.031) and disease activity index (DAI) score (OR: 53.928, 95%CI: 3.822-760.948, P = 0.003) as independent predictors of SARE. CONCLUSION: Anal bulge rating (> 0.500 grade) and DAI score (> 2.165 points) can predict SARE. The nomogram shows potential value in clinical practice.

Quality evaluation of guidelines for the diagnosis and treatment of radiation enteritis.

OBJECTIVE: To systematically evaluate the guidelines for the diagnosis and treatment of radioactive enteritis, compare their differences and reasons and provide some reference for updating them. METHODS: This study used guidelines related to radiation enteritis by searching a database. Four independent reviewers used the AGREE II evaluation tool to evaluate the quality of the included guidelines, collate their main recommendations, and analyze the highest evidence supporting the main recommendations. RESULTS: Six diagnostic and therapeutic guidelines for radiation enteritis were included in this study, one of which, the American Society for Gastrointestinal Endoscopy guidelines, had an overall score of over 60%, which is worthy of clinical recommendation. In the diagnosis and treatment of radioactive rectal injury, the recommendations for hemorrhagic endoscopic treatment are mature and mainly include (I) argon plasma coagulation; (II) formalin treatment; (III) bipolar electrocoagulation; (IV) heater probe; (V) radiofrequency ablation; and (VI) cryoablation. CONCLUSION: The methodological quality of radioactive enteritis guidelines is unequal; even in the same guidelines, different domains have a large difference. For radioactive rectal damage diagnosis, a type of endoscopic treatment recommendation is more mature, but the overall diagnosis and treatment of radioactive enteritis still lacks high-quality research evidence.

Treatment of Radiation Enteritis With Fecal Transplantation.

Radiation enteritis (RE) is a frequent complication in patients who undergo pelvic irradiation, and this condition has been increasingly diagnosed. Fecal microbiota transplantation (FMT) is being developed in recent years, and it has remarkable curative effect for the clostridium and inflammatory bowel disease. Herein, we present a case of recurrent RE in a 59-year-old woman with RE 18 years after radiotherapy for cervical carcinoma. Fecal microbiota transplantation therapy with intestinal flora from her 18-year-old son was applied and was successful in relieving the symptoms. To the best of our knowledge, this study is the first case report of FMT in a patient with RE.

CXCL16 inhibits epithelial regeneration and promotes fibrosis during the progression of radiation enteritis.

Radiation enteritis (RE) is a prevalent complication of radiotherapy for pelvic malignant tumors, characterized by severe intestinal epithelial destruction and progressive submucosal fibrosis. However, little is known about the pathogenesis of this disease, and so far, there is no specific targeted therapy. Here, we report that CXCL16 is upregulated in the injured intestinal tissues of RE patients and in a mouse model. Genetic deletion of Cxcl16 mitigates fibrosis and promotes intestinal stem cell-mediated epithelial regeneration after radiation injury in mice. Mechanistically, CXCL16 functions on myofibroblasts through its receptor CXCR6 and activates JAK3/STAT3 signaling to promote fibrosis and, at the same time, to transcriptionally modulate the levels of BMP4 and hepatocyte growth factor (HGF) in myofibroblasts. Moreover, we find that CXCL16 and CXCR6 auto- and cross-regulate themselves in positive feedback loops. Treatment with CXCL16 neutralizing monoclonal antibody attenuates fibrosis and improves the epithelial repair in RE mouse model. Our findings emphasize the important role of CXCL16 in the progression of RE and suggest that CXCL16 signaling could be a potential therapeutic target for RE. © 2022 The Pathological Society of Great Britain and Ireland.

[Effect and mechanism of Rho kinase inhibitor on intestinal injury in septic rats].

OBJECTIVE: To explore the effect of Rho kinase inhibitor on intestinal injury in septic rats and its possible mechanism. METHODS: Thirty-two male Sprague-Dawley (SD) rats were randomly divided into sham operation group (Sham group), Rho kinase inhibitor Y-27632 control group (Y+Sham group), sepsis model group [cecal ligation and puncture (CLP) group] and Y-27632 pretreatment group (Y+CLP group), with 8 rats in each group. Rat sepsis model was reproduced by CLP. The rats in the Sham group and Y+Sham group were only separated and moved the cecum without ligation and perforation. The rats in the Y+Sham group and Y+CLP group were pretreated with intraperitoneal injection of Y-27632 solution 5 mg/kg 15 minutes before operation; the rats in the Sham group and CLP group were intraperitoneally injected with the same amount of phosphate buffered saline (PBS). Twenty-four hours after operation, the heart blood was collected and the serum diamine oxidase (DAO) content was determined by enzyme-linked immunosorbent assay (ELISA). Then the small intestine tissue was collected, the pathological changes of the intestinal tissue were observed under the light microscope after hematoxylin-eosin (HE) staining, and Chiu's score was performed. The positive expressions of Rho-related coiled-coil kinase 1 (ROCK1) and nuclear factor-κB (NF-κB) in intestinal tissue were detected by immunohistochemistry. ELISA was used to detect the levels of tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) in intestinal tissue homogenate. RESULTS: The intestinal tissue structure of the Sham group and Y+Sham group was intact and the mucosa was arranged neatly. Compared with the Sham group, the intestinal mucosa of the CLP group was arranged disorderly, with a large number of inflammatory cells infiltration, and the Chiu's score was significantly increased (3.83±0.27 vs. 0.12±0.11, P < 0.05), indicating that those rats suffered from septic intestinal injury. Compared with the CLP group, the degree of necrosis of intestinal epithelial cells in the Y+CLP group was reduced, a small amount of inflammatory cells infiltration was seen, and the Chiu's score was significantly decreased (2.85±0.21 vs. 3.83±0.27, P < 0.05), indicating that Y-27632 pretreatment could alleviate intestinal injury in septic rats. Compared with the Sham group, the positive expressions of intestinal tissue ROCK1 and NF-κB, the contents of serum DAO and intestinal homogenate TNF-α in the CLP group were significantly increased [ROCK1 expression (A value): 0.19 (0.18, 0.22) vs. 0.10 (0.09, 0.11), NF-κB expression (A value): 0.40±0.02 vs. 0.15±0.01, DAO (ng/L): 287.81±23.31 vs. 144.92±17.72, TNF-α (ng/L): 101.08±5.62 vs. 74.81±5.56, all P < 0.05], the level of intestinal homogenate IL-10 was significantly decreased (µg/L: 55.16±5.20 vs. 95.95±7.53, P < 0.05). Compared with the CLP group, the positive expressions of intestinal tissue ROCK1, NF-κB, the contents of serum DAO and intestinal homogenate TNF-α in the Y+CLP group were significantly decreased [ROCK1 expression (A value): 0.15 (0.13, 0.18) vs. 0.19 (0.18, 0.22), NF-κB expression (A value): 0.28±0.01 vs. 0.40±0.02, DAO (ng/L): 243.34±19.76 vs. 287.81±23.31, TNF-α (ng/L): 90.41±8.79 vs. 101.08±5.62, all P < 0.05], while the level of intestinal homogenate IL-10 was significantly increased (µg/L: 66.15±5.74 vs. 55.16±5.20, P < 0.05), indicating that the protective effect of Y-27632 pretreatment on sepsis intestinal injury rats might be related to the regulation of RhoA/ROCK1/NF-κB signaling pathway. CONCLUSIONS: Rho kinase inhibitors can reduce intestinal injury in septic rats, and the mechanism may be related to inhibiting RhoA/ROCK1/NF-κB signaling pathway and reducing intestinal inflammation in septic rats.

A Case of Lupus Enteritis in Which Multiple Colorectal Ulcers Were the Only Signs of Relapse.

The patient was a 62-year-old woman. She had been treated for systemic lupus erythematosus (SLE) for 15 years and had a stable clinical course with cyclosporine, prednisolone, and ticlopidine. She experienced anal pain, diarrhea, and bloody stools for four months. Colonoscopy showed scattered large and small punchedout ulcers in the colon and deep longitudinal ulcers in the sigmoid colon. Blood test results indicated low SLE activity. Culture of mucosal biopsy did not reveal any findings. Computed tomography showed intestinal membrane arteriovenous dilatation (comb sign), therefore lupus enteritis was suspected. After initiating endoxan pulse therapy, symptoms improved rapidly. Disappearance of ulcers was confirmed by endoscopic images.

Centella asiatica-Derived Endothelial Paracrine Restores Epithelial Barrier Dysfunction in Radiation-Induced Enteritis.

Radiation-induced enteritis is frequently observed following radiotherapy for cancer or occurs due to radiation exposure in a nuclear accident. The loss of the epithelial integrity leads to 'leaky gut', so recovery of damaged epithelium is an important strategy in therapeutic trials. Centella asiatica (CA), a traditional herbal medicine, is widely used for wound healing by protecting against endothelial damage. In this study, we investigated the radio-mitigating effect of CA, focusing on the crosstalk between endothelial and epithelial cells. CA treatment relieved radiation-induced endothelial dysfunction and mitigated radiation-induced enteritis. In particular, treatment of the conditioned media from CA-treated irradiated endothelial cells recovered radiation-induced epithelial barrier damage. We also determined that epidermal growth factor (EGF) is a critical factor secreted by CA-treated irradiated endothelial cells. Treatment with EGF effectively improved the radiation-induced epithelial barrier dysfunction. We also identified the therapeutic effects of CA-induced endothelial paracrine in a radiation-induced enteritis mouse model with epithelial barrier restoration. Otherwise, CA treatment did not show radioprotective effects on colorectal tumors in vivo. We showed therapeutic effects of CA on radiation-induced enteritis, with the recovery of endothelial and epithelial dysfunction. Thus, our findings suggest that CA is an effective radio-mitigator against radiation-induced enteritis.

[Stenotic ischemic enteritis secondary to intraperitoneal band infiltration: a case report].

A 55-year-old man presented with vomiting and upper abdominal pain. Two months later, computed tomography revealed jejunal wall thickening and contrast enhancement. Double-balloon endoscopy revealed severe jejunal stenosis and mucosal prolapse. The patient was diagnosed with stenotic ischemic small bowel inflammation and underwent partial small bowel resection. Clinicians should consider intraperitoneal band formation in the differential diagnosis of patients without a history of abdominal surgery or trauma. Surgical resection should be considered to prevent strangulation ileus.