Segmental Colitis Associated with Diverticulosis (SCAD).

PURPOSE OF REVIEW: A distinctive, possibly "novel" form of a segmental inflammatory colonic disease process associated with diverticular disease (so-called SCAD or segmental-colitis-associated-diverticulosis) is reviewed. RECENT FINDINGS: Although this phenotype of inflammatory colonic disease was initially recognized decades ago, mainly in the elderly, recent evidence from long term natural history studies along with meta-analyses confirms that its clinical course is usually benign and drug-responsive. Interestingly, its appearance in some treated with monoclonal agents (eg., ipilimumab associated colitis) or infected with coronavirus-19 may have critical implications for its pathogenesis. This review further explores the implications of recognition of this pattern of colonic inflammatory disease, with relevance for physicians involved in both clinical practice and clinical trials of newer therapeutic agents.

Colitis as the Main Presentation of COVID-19: A Case Report.

The main symptoms of coronavirus disease (COVID-19) are fever, cough, tiredness, and loss of smell and taste. Gastrointestinal symptoms are less common. A 38-year-old female patient, previously healthy, presented with a history of hematochezia up to 8 times per day, followed by abdominal cramps, urgency, and chills for two days. She did not have any respiratory symptoms and was previously vaccinated for COVID-19. She was afebrile, with normal vital signs. Blood samples showed normal complete blood count and increased C-reactive protein (CRP), fibrinogen, and D-dimer levels (66 mg/L, 4.1 g/L, and 2302 µ/L FEU, respectively). Stool samples for stool culture, C. difficile, and viral examination came back negative. On day 3, she reported a mild cough, fever and loss of smell and taste. Nasopharyngeal swab for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) PCR test came back positive. On day 6, the patient still had hematochezia accompanied by abdominal cramps, but fever and respiratory symptoms withdrew. CRP, fibrinogen, and D-dimers were still elevated, as well as liver enzyme levels. Sigmoidoscopy was performed with biopsies taken from sigmoid and rectum for histology and PCR SARS-CoV-2 testing. CT angiography showed no signs of thrombosis in mesenteric veins or arteries. PCR test for SARS-CoV-2 virus from rectal biopsy sample was positive. Patient was treated with methylprednisolone iv for two days and peroral prednisone afterwards, with mesalamine, metronidazole and enoxaparin. Sigmoidoscopy was repeated after two weeks showing only mild hyperemia. At that time, the patient had normal stool, normal CRP, liver enzyme, fibrinogen, and D-dimer levels, and normocytic anemia (hemoglobin level of 103 g/L). We wanted to show that severe gastrointestinal symptoms, such as hemorrhagic colitis, can be the main presentation of COVID-19, even in young patients with no prior comorbidities. In such a case, PCR test in biopsy samples can be performed to prove SARS-CoV-2 infection of bowel mucosa.

The colonic interleukin-19 aggravates the dextran sodium sulfate/stress-induced comorbidities due to colitis and anxiety.

Comorbidities due to inflammatory bowel disease (IBD) and anxiety are commonly acknowledged; however, their underlying basis is unclear. In the current study, we first conducted a clinical retrospective analysis to identify the enhancive incidence rate of IBD before or after the epidemic of Corona Virus Disease 2019 (COVID-19), with higher Generalized Anxiety Disorder-7 (GAD-7), as well as poorer Gastrointestinal Quality of Life Index (GIQLI). Then, the dextran sodium sulfate (DSS) and chronic unpredictable stress (CUS)-induced IBD and anxiety comorbid models were established with the correlational relations between symptoms of IBD and anxiety-related behaviors. We found dysfunctional up-regulation of a new inflammatory factor interleukin (IL)-19 in the colon of DSS/CUS treated mice. Overexpression of IL-19 in colon induced anxious phenotypes, and accelerated the anxious condition and symptoms of colitis in the DSS/CUS model by promoting the expression of inducible nitric oxide synthase (iNOS), IL-1ß, and IL-6 pro-inflammatory factors, and activating signal transducer and activator of transcription 3 (STAT3) signaling pathway in the colon. Furthermore, overexpression of IL-19 in the colon also reduced the expression levels of brain-derived neurotrophic factor (BDNF), extracellular signal-regulated kinase (ERK), and cAMP-response element binding protein (CREB) signaling pathways activity in the hippocampus. These results suggest that IL-19 was a pivotal player in DSS/CUS-induced comorbidities of colitis and anxiety with different signaling pathways for the colon and hippocampus, which provides a candidate gene to explore the pathophysiology of comorbidities due to colitis and anxiety.

Colitis with Hypereosinophilia following the Second Dose of the BNT162b2 mRNA COVID-19 Vaccine: A Case Report with a Literature Review.

A 61-year-old man presented with a 7-day history of watery diarrhea and loss of appetite after receiving the second dose of the Pfizer-BioNTech COVID-19 vaccine. Laboratory studies showed significant eosinophilia and an elevated IgE level (white cell count, 18.4×109/L; eosinophil count, 9.5×109/L; and IgE level, 540 IU/L). Symptoms resolved 10 days after vaccination without any steroids or antiallergic medications, and the eosinophil count had also returned to within normal limits 2 months later. Several cases of eosinophilic disorders following receipt of any type of injectable COVID-19 vaccine have been reported, so the etiology should be examined.

A descriptive study of abdominal complications in patients with mild COVID-19 presenting to the emergency department: a single-center experience in Japan during the omicron variant phase.

BACKGROUND: COVID-19 is widely known to induce a variety of extrapulmonary manifestations. Gastrointestinal symptoms have been identified as the most common extra-pulmonary manifestations of COVID-19, with an incidence reported to range from 3 to 61%. Although previous reports have addressed abdominal complications with COVID-19, these have not been adequately elucidated for the omicron variant. The aim of our study was to clarify the diagnosis of concomitant abdominal diseases in patients with mild COVID-19 who presented to hospital with abdominal symptoms during the sixth and seventh waves of the pandemic of the omicron variant in Japan. METHODS: This study was a retrospective, single-center, descriptive study. In total, 2291 consecutive patients with COVID-19 who visited the Department of Emergency and Critical Care Medicine, Kansai Medical University Medical Center, Osaka, Japan, between January 2022 and September 2022 were potentially eligible for the study. Patients delivered by ambulance or transferred from other hospitals were not included. We collected and described physical examination results, medical history, laboratory data, computed tomography findings and treatments. Data collected included diagnostic characteristics, abdominal symptoms, extra-abdominal symptoms and complicated diagnosis other than that of COVID-19 for abdominal symptoms. RESULTS: Abdominal symptoms were present in 183 patients with COVID-19. The number of patients with each abdominal symptom were as follows: nausea and vomiting (86/183, 47%), abdominal pain (63/183, 34%), diarrhea (61/183, 33%), gastrointestinal bleeding (20/183, 11%) and anorexia (6/183, 3.3%). Of these patients, 17 were diagnosed as having acute hemorrhagic colitis, five had drug-induced adverse events, two had retroperitoneal hemorrhage, two had appendicitis, two had choledocholithiasis, two had constipation, and two had anuresis, among others. The localization of acute hemorrhagic colitis was the left-sided colon in all cases. CONCLUSIONS: Our study showed that acute hemorrhagic colitis was characteristic in mild cases of the omicron variant of COVID-19 with gastrointestinal bleeding. When examining patients with mild COVID-19 with gastrointestinal bleeding, the potential for acute hemorrhagic colitis should be kept in mind.

The gastrointestinal effects of COVID­19 infection during childhood and among the children affected with inflammatory bowel disease / A COVID-19-fertozés gastrointestinalis hatásai gyermekkorban és a gyulladásos bélbeteg gyermekekben.

Összefoglaló. A SARS-CoV-2-infekció változatos kórlefolyású, a gyermekpopulációban növekvo incidenciát mutató fertozés. Ebben a korcsoportban a felnottekkel szemben sokkal gyakrabban tapasztalhatók gasztroenterológiai tünetek a betegség során, 18-32%-ban jelentkezik legalább egy szimptóma. Ezek nem specifikusak, gyakran megegyezhetnek a virális enteritisek, a gyulladásos bélbetegségek vagy a vakbélgyulladás tüneteivel. A gyermekkori SARS-CoV-2-infekciónak egy viszonylag ritkán megjeleno, de súlyos, akár életveszélyes szövodménye a gyermekkori sokszervi gyulladásos szindróma (multisystem inflammatory syndrome in children, MIS-C). Ilyenkor a gastrointestinalis tünetek gyakorisága 60-100%-ra no, sok esetben akut has benyomását keltve. A jelenlegi kutatások eredményei alapján a gyulladásos bélbeteg gyerekek az alapbetegségük miatt nincsenek nagyobb veszélynek kitéve az átlagpopulációhoz képest a COVID-19-fertozés szempontjából. A terápiájukban alkalmazott gyógyszereik közül a nagy dózisú szteroidkezelés okoz nagyobb kockázatot a megfertozodésre, illetve ebben az esetben a súlyosabb kórlefolyásra. Az éppen remisszióban lévo gyulladásos bélbetegek fenntartó terápiájának módosítások nélküli folytatása javasolt, kiemelt figyelmet fordítva a biológiai terápiák idoben történo, megszakítás nélküli alkalmazására. Törekedni kell a személyes vizitek számának csökkentésére a pandémia idején, ezek telemedicinával történo helyettesítése javasolt. A halasztható endoszkópos vizsgálatok noninvazív vizsgálómódszerekkel történo átmeneti kiváltása részesítendo elonyben a betegség aktivitásának, a terápia hatékonyságának megítélésére. A gyulladásos bélbetegségben szenvedo gyermekek COVID-19 elleni védooltása javasolt, jelenleg minden elérheto oltóanyag alkalmazható náluk (az élo ágenst tartalmazó vakcinák ellenjavalltak). Immunmoduláns, szteroid- vagy anti-tumornekrózisfaktor (TNF)-alfa-terápia esetén az oltás lehetséges csökkent hatékonyságával kell számolni. Orv Hetil. 2022; 163(6): 214-221. Summary. The SARS-CoV-2 infection is showing high variety in the disease course, with a constantly increasing incidence among the pediatric population. In this age group, at least one gastrointestinal symptom appears in 18-32% of the cases, showing a significant difference compared to the adult population. The gastrointestinal signs of COVID-19 are not specific, can mimic the symptoms of viral enteritis, inflammatory bowel diseases or acute appendicitis. The multisystem inflammatory syndrome in children (MIS-C) is a rather rare, but serious complication of the pediatric COVID-19 disease: in these cases, the incidence of the gastrointestinal symptoms is increased up to 60-100%, often observed as acute abdomen. Based on recent researches, patients with inflammatory bowel diseases (IBD) are shown to have the same risk in developing COVID-19 infection compared to the normal population: in their medications, the high dose steroid treatment is proved to increase the risk of infection or to make the disease course more serious. The treatment of patients with IBD should be continued without any changes (when the disease is in remission). The use of biologics should be done with special care, with more attention keeping the schedule and the continuity. It is advised to minimise the number of personal visits during the pandemic, they should be substituted with telemedicine. The postponable endoscopic examinations should be temporarily redeemed by non-invasive methods for screening the disease activity and the efficacy of the treatment. The vaccination against COVID-19 is advised in the population with IBD. All vaccines currently available are usable in this patient group (the use of vaccines containing live agents are contraindicated). In the case of patients treated with immunmodulators, steroids or anti-tumor necrosis factor (TNF) alpha, a possible lower efficacy can be expected after the vaccination. Orv Hetil. 2022; 163(6): 214-221.

SARS-CoV-2 shifts transcription of host gene to increase Spike acylation and boost infectivity (preprint)

SARS-CoV-2 infection requires Spike protein mediating fusion between the viral and cellular membranes. The fusogenic activity of Spike requires its post-translational lipid modification by host S-acyltransferases, predominantly ZDHHC20. Previous observations indicate that SARS-CoV-2 infection augments the S-acylation of Spike when compared to transfection. Here, we find that SARS-CoV-2 infection triggers a change in the transcriptional start site of the zddhc20 gene, both in cells and in an in vivo infection model, resulting in a 67-amino–acid-long N-terminally extended protein with 37-times higher Spike acylating activity, leading to enhanced viral infectivity. Furthermore, we observed the same induced transcriptional change in response to other challenges, such as chemically induced colitis, indicating that SARS-CoV-2 hijacks an existing cell damage response pathway to generate more infectious viruses.

SARS-CoV-2 shifts transcription of host gene to increase Spike acylation and boost infectivity (preprint)

SARS-CoV-2 infection requires Spike protein mediating fusion between the viral and cellular membranes. The fusogenic activity of Spike requires its post-translational lipid modification by host S-acyltransferases, predominantly ZDHHC20. Previous observations indicate that SARS-CoV-2 infection augments the S-acylation of Spike when compared to transfection. Here, we find that SARS-CoV-2 infection triggers a change in the transcriptional start site of the zddhc20 gene, both in cells and in an in vivo infection model, resulting in a 67-amino-acid-long N-terminally extended protein with 37-times higher Spike acylating activity, leading to enhanced viral infectivity. Furthermore, we observed the same induced transcriptional change in response to other challenges, such as chemically induced colitis, indicating that SARS-CoV-2 hijacks an existing cell damage response pathway to generate more infectious viruses.

Opuntia ficus indica (L.) Mill. An Ancient Plant Source of Nutraceuticals.

Opuntia ficus-indica (L.) Mill. (OFI) is a plant with numerous beneficial properties known in traditional medicine. It has been a domesticated plant in Latin America, Africa, Mediterranean countries, the Middle East, India and Australia. Nowadays, the research concentrates on natural compounds to lower costs and the possible side effects of synthetic compounds. The use of nutraceuticals, bioactive compounds of vegetable origin with important nutritional values, is encouraged. OFI has shown numerous activities due to its high content of antioxidants, including flavonoids and ascorbate, pigments, carotenoids and betalains, phenolic acids and other phytochemical components, such as biopeptides and soluble fibers. The most important effects of OFI are represented by the activity against acne, arthrosis, dermatosis, diabetes, diarrhea, fever, high blood pressure, prostatitis, rheumatism, stomachache, tumor, wart, allergy, wound, colitis and some viral diseases. Moreover, a promising role has been suggested in inflammatory bowel disease, colitis and metabolic syndrome. The most recent studies addressed the role of OFI in preventing and treating COVID-19 disease. In light of the above, this review summarizes the biological activities and health benefits that this plant may exert.

Xuanfei Baidu decoction attenuates intestinal disorders by modulating NF-κB pathway, regulating T cell immunity and improving intestinal flora.

BACKGROUND: A number of studies have shown that gastrointestinal manifestations co-exist with respiratory symptoms in coronavirus disease 2019 (COVID-19) patients. Xuanfei Baidu decoction (XFBD) was recommended by the National Health Commission to treat mild and moderate COVID-19 patients and proved to effectively alleviate intestinal symptoms. However, the exact mechanisms remain elusive. PURPOSE: This study aimed at exploring potential mechanisms of XFBD by utilizing a mouse model of dextran sulfate sodium (DSS)-induced acute experimental colitis, mimicking the disease conditions of intestinal microecological disorders. METHODS: The network pharmacology approach was employed to identify the potential targets and pathways of XFBD on the intestinal disorders. Mice with DSS-induced intestinal disorders were utilized to evaluate the protective effect of XFBD in vivo, including body weight, disease activity index (DAI) score, colon length, spleen weight, and serum tumor necrosis factor-α (TNF-α) level. Colon tissues were used to perform hematoxylin-eosin (H&E) staining, western blot analysis, and transcriptome sequencing. Macrophages, neutrophils and the proportions of T helper cell (Th) 1 and Th2 cells were measured by flow cytometry. Intestinal contents were collected for 16S rRNA gene sequencing. RESULTS: Network pharmacology analysis indicated that XFBD inhibited the progression of COVID-19-related intestinal diseases by repressing inflammation. In mice with DSS-induced intestinal inflammation, XFBD treatment significantly reduced weight loss, the spleen index, the disease activity index, TNF-α levels, and colonic tissue damage, and prevented colon shortening. Transcriptomics and flow cytometry results suggested that XFBD remodeled intestinal immunity by downregulating the Th1/Th2 ratio. Western blot analysis showed that XFBD exerted its anti-inflammatory effects by blocking the nuclear factor-κB (NF-κB) signaling pathway. Indicator analysis of microbiota showed that 75 operational taxonomic units (OTUs) were affected after XFBD administration. Among them, Akkermansia, Muribaculaceae, Lachnospiraceae, and Enterorhabdus were simultaneously negatively correlated with intestinal disorders' parameters, and Bacteroides, Escherichia-Shigella, Eubacterium nodatum,Turicibacter, and Clostridium sensu stricto 1, showed positive correlations with intestinal disorders' parameters. CONCLUSIONS: Our data indicate that XFBD treatment attenuated intestinal disorders associated with inhibiting inflammation, remodeling of intestinal immunity, and improving intestinal flora. These findings provide a scientific basis for the clinical use of XFBD and offer a potential therapeutic approach for the treatment of COVID-19 patients with intestinal symptoms.

Cytomegalovirus-related colitis in patients with inflammatory bowel disease.

PURPOSE: We aimed to examine the role of cytomegalovirus (CMV) infection in patients with inflammatory bowel disease (IBD), which remains highly debated. METHODS: Retrospective, observational study using the Nationwide Inpatient Sample (NIS) 2015-2017. Patients with ICD9/10CM codes for Crohn's disease (CD), ulcerative colitis (UC), and CMV colitis were included in the study. The primary outcome was the odds of CMV colitis in patients with IBD compared to patients without IBD. Secondary outcomes were differences in inpatient morbidity, mortality, resource utilization, colectomy rates, hospital length of stay (LOS), and inflation-adjusted total hospitalization costs. RESULTS: A total of 992,445 patients with IBD were identified, out of which 520 (0.05%) had associated CMV colitis. Patients with IBD had significantly higher odds of CMV colitis compared to patients without IBD (aOR: 19.76, p < 0.01), having an even greater association with UC (aOR: 31.13, p < 0.01). CMV colitis in patients with CD was associated with a significant increase in odds of mortality, shock, and ICU stay, while patients with UC had higher odds of colectomy. The patients with IBD and CMV colitis had higher odds of acute kidney injury, multiorgan failure, markedly increased additional hospital costs, and LOS compared to patients with IBD and no CMV colitis. CONCLUSION: IBD has a significant association with CMV colitis, and the presence of CMV colitis in patients with IBD was associated with higher mortality, morbidity, and hospital costs. Prospectively designed studies may better elucidate the risk factors and impact of CMV colitis on patients with IBD.

Inflammatory Bowel Disease: Clinical Diagnosis and Surgical Treatment-Overview.

This article is an overview of guidelines for the clinical diagnosis and surgical treatment of predominantly colonic inflammatory bowel diseases (IBD). This overview describes the systematically and comprehensively multidisciplinary recommendations based on the updated principles of evidence-based literature to promote the adoption of best surgical practices and research as well as patient and specialized healthcare provider education. Colonic IBD represents idiopathic, chronic, inflammatory disorders encompassing Crohn's colitis (CC) and ulcerative colitis (UC), the two unsolved medical subtypes of this condition, which present similarity in their clinical and histopathological characteristics. The standard state-of-the-art classification diagnostic steps are disease evaluation and assessment according to the Montreal classification to enable explicit communication with professionals. The signs and symptoms on first presentation are mainly connected with the anatomical localization and severity of the disease and less with the resulting diagnosis "CC" or "UC". This can clinically and histologically be non-definitive to interpret to establish criteria and is classified as indeterminate colitis (IC). Conservative surgical intervention varies depending on the disease phenotype and accessible avenues. The World Gastroenterology Organizations has, for this reason, recommended guidelines for clinical diagnosis and management. Surgical intervention is indicated when conservative treatment is ineffective (refractory), during intractable gastrointestinal hemorrhage, in obstructive gastrointestinal luminal stenosis (due to fibrotic scar tissue), or in the case of abscesses, peritonitis, or complicated fistula formation. The risk of colitis-associated colorectal cancer is realizable in IBD patients before and after restorative proctocolectomy with ileal pouch-anal anastomosis. Therefore, endoscopic surveillance strategies, aimed at the early detection of dysplasia, are recommended. During the COVID-19 pandemic, IBD patients continued to be admitted for IBD-related surgical interventions. Virtual and phone call follow-ups reinforcing the continuity of care are recommended. There is a need for special guidelines that explore solutions to the groundwork gap in terms of access limitations to IBD care in developing countries, and the irregular representation of socioeconomic stratification needs a strategic plan for how to address this serious emerging challenge in the global pandemic.

GLP-1 Mediates Regulation of Colonic ACE2 Expression by the Bile Acid Receptor GPBAR1 in Inflammation.

BACKGROUND & AIMS: ACE2, a carboxypeptidase that generates Ang-(1-7) from Ang II, is highly expressed in the lung, small intestine and colon. GPBAR1, is a G protein bile acid receptor that promotes the release of the insulinotropic factor glucagon-like peptide (GLP)-1 and attenuates intestinal inflammation. METHODS: We investigated the expression of ACE2, GLP-1 and GPBAR1 in two cohorts of Crohn's disease (CD) patients and three mouse models of colitis and Gpbar1-/- mice. Activation of GPBAR1 in these models and in vitro was achieved by BAR501, a selective GPBAR1 agonist. RESULTS: In IBD patients, ACE2 mRNA expression was regulated in a site-specific manner in response to inflammation. While expression of ileal ACE2 mRNA was reduced, the colon expression was induced. Colon expression of ACE2 mRNA in IBD correlated with expression of TNF-α and GPBAR1. A positive correlation occurred between GCG and GPBAR1 in human samples and animal models of colitis. In these models, ACE2 mRNA expression was further upregulated by GPABR1 agonism and reversed by exendin-3, a GLP-1 receptor antagonist. In in vitro studies, liraglutide, a GLP-1 analogue, increased the expression of ACE2 in colon epithelial cells/macrophages co-cultures. CONCLUSIONS: ACE2 mRNA expression in the colon of IBD patients and rodent models of colitis is regulated in a TNF-α- and GLP-1-dependent manner. We have identified a GPBAR1/GLP-1 mechanism as a positive modulator of ACE2.