Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 18 de 18
Filter
1.
Journal of Functional Foods ; 100, 2023.
Article in English | Web of Science | ID: covidwho-2210773

ABSTRACT

Fructose-rich beverages and foods consumption correlates with the epidemic rise in cardiovascular disease, diabetes and obesity. Severity of COVID-19 has been related to these metabolic diseases. Fructose-rich foods could place people at an increased risk for severe COVID-19. We investigated whether maternal fructose intake in offspring affects hepatic and ileal gene expression of proteins that permit SARS-CoV2 entry to the cell. Carbo-hydrates were supplied to pregnant rats in drinking water. Adult and young male descendants subjected to water, liquid fructose alone or as a part of a Western diet, were studied. Maternal fructose reduced hepatic SARS-CoV2 entry factors expression in older offspring. On the contrary, maternal fructose boosted the Western diet-induced increase in viral entry factors expression in ileum of young descendants. Maternal fructose intake produced a fetal programming that increases hepatic viral protection and, in contrast, exacerbates fructose plus cholesterol -induced diminution in SARS-CoV2 protection in small intestine of progeny.

2.
Scientific Reports (Nature Publisher Group) ; 12(1), 2022.
Article in English | ProQuest Central | ID: covidwho-2186018

ABSTRACT

Agricultural residues can be used as alternative feed sources in industrial chicken production. The impacts of different levels of pomegranate peel and waste cooking oil as an agricultural residue on broilers' nutrition were investigated. Results showed that the replacement of 8% pomegranate peel in diets decreased the growth performance of broilers. Supplementing 8% pomegranate peel in diets reduced apparent nutrient digestibility. The highest level of waste oil inclusion in broiler diets indicated negative impacts on apparent zmetabolizable energy and crude fat apparent nutrients digestibility. Broilers fed the diet containing 4% pomegranate peel had a higher Lactobacillus population. The results showed that the Lactobacillus population was lower in broilers fed 8% pomegranate peel powder and 4% waste oil in diets. The inclusion of 8% pomegranate peel powder in diets showed lower villus height and crypt depth in the duodenum, jejunum, and ileum. The inclusion of 4% pomegranate peel decreased the peroxide value (PV) of meat. Dietary inclusion of 4% waste oil raised the PV of meat. Alpha-tocopherol supplementation decreased the PV of meat. Finally, the results provide information that 4% of pomegranate peel and 4% waste oil could be used as an alternative feed ingredient in broiler diets without adverse effects.

3.
Chest ; 162(4):A1120, 2022.
Article in English | EMBASE | ID: covidwho-2060774

ABSTRACT

SESSION TITLE: Critical Gastrointestinal Case Reports SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: Histoplasma capsulatum is a dimorphic fungus most commonly encountered as an opportunistic infection in immunosuppressed patients, particularly those with HIV/AIDS. However, patients immunosuppressed from other causes can also be at risk. Here is presented the case of a patient on multi-immunosuppressant therapy as treatment for Crohn's disease, who developed disseminated histoplasmosis. CASE PRESENTATION: A 44-year-old male with a past medical history of Crohn's disease (previously been on azathioprine, adalimumab and currently on Prednisone therapy), recently started on infliximab infusion for uncontrolled symptoms of IBD, diabetes mellitus, hypothyroidism, and COVID-19 infection (not requiring oxygen therapy) one month prior to the current admission initially presented to the hospital with chief complaints of exacerbated weakness, myalgias, fevers and diarrhea for 5 days;Symptoms of weakness, myalgias began after first infusion of infliximab and it got progressively worse after the 2nd infusion 2 weeks prior to the admission. White Blood Cell count was 1.1 K/uL, platelet count was 7 K/uL, hemoglobin was 7.9 g/dL. CRP was elevated to 142 mg/L, and ferritin was elevated to 39,000 ug/L. CT abdomen and pelvis demonstrated probable rectosigmoid colitis and splenomegaly. Subsequent chest x-ray demonstrated bilateral opacities with haziness over bilateral lung fields. Respiratory viral panel, stool panel, blastomyces antigen, cryptococcal antigen, toxoplasma antibodies, HIV antibody, CMV PCR, and blood cultures were unrevealing. Urinary histoplasma antigen was positive, and BD-glucan was elevated to over 500 ng/L. EBV panel was positive for reactivation, with EBV DNA 2.02 IU/mL. He was subsequently started on amphotericin B lipid complex, with itraconazole destination therapy. He was treated empirically for pneumocystis jiroveci pneumonia (PJP) with sulfamethoxazole-trimethoprim due to him being on chronic Prednisone therapy. Echocardiogram demonstrated left ventricular ejection fraction (LVEF) of 40%, with diffuse hypokinesis and wall motion abnormalities, posing some question of myocarditis. He was later discharged home in an improved state. DISCUSSION: Disseminated histoplasmosis in the setting of Crohn's disease on chronic immunosuppressive therapy has been very rarely reported,(1) with similar reports in patients on immunosuppressive therapy in the setting of rheumatologic disease being slightly more common.(2) The most commonly involved areas in gastrointestinal histoplasmosis are the terminal ileum and colon,(3) with this patient's rectosigmoid colitis and symptomatology being consistent with this pattern. The patient's myocarditis is also consistent with disseminated histoplasmosis infection. CONCLUSIONS: Clinicians should maintain suspicion for opportunistic infections in patients on immunosuppressive therapy in the setting of critical illness. Reference #1: Bhut, B., Kulkarni, A., Rai, V. et al. A rare case of disseminated histoplasmosis in a patient with Crohn's disease on immunosuppressive treatment. Indian J Gastroenterol 37, 472–474 (2018). https://doi.org/10.1007/s12664-018-0886-1 Reference #2: Wood KL, Hage CA, Knox KS, et al. Histoplasmosis after treatment with anti-tumor necrosis factor-alpha therapy. Am J Respir Crit Care Med. 2003;167(9):1279-1282. doi:10.1164/rccm.200206-563OC Reference #3: Galandiuk S, Davis BR. Infliximab-induced disseminated histoplasmosis in a patient with Crohn's disease. Nat Clin Pract Gastroenterol Hepatol. 2008;5(5):283-287. doi:10.1038/ncpgasthep1119 DISCLOSURES: no disclosure on file for Donald Dumford;No relevant relationships by Abhilash Bhat Marakini No relevant relationships by Palak Rath No relevant relationships by Sterling Shriber

4.
Chest ; 162(4):A855, 2022.
Article in English | EMBASE | ID: covidwho-2060708

ABSTRACT

SESSION TITLE: COVID-19 Co-Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: We present a case of Eggerthella bacteremia in a patient with COVID-19. CASE PRESENTATION: A 69-year-old woman presented to the emergency room with chief complaint of cough, dyspnea, and malaise. After testing positive with a home COVID-19 test three days earlier, she continued to have worsening respiratory status and was brought in via ambulance. She was found to be tachycardic and hypoxic, requiring high-flow oxygen to maintain saturation in the emergency department. Chest X-ray showed bilateral patchy opacities consistent with multifocal COVID-19 pneumonia, and she was admitted to the intensive care unit for acute hypoxic respiratory failure. COVID-19 drug therapy was initiated, including baricitinib, remdesivir and decadron. Shortly after hospitalization, she began to endorse worsening abdominal pain. Physical exam elicited tenderness to palpation of her right lower quadrant. Abdominal CT scan showed distal ileum fluid collection concerning for possible bowel perforation. She underwent exploratory laparotomy which confirmed perforation, and a small bowel resection with anastomosis was performed. Blood cultures were positive for gram-positive bacilli, which were further identified as Eggerthella species. She required mechanical ventilation for worsening respiratory function post-surgery but remained unresponsive on the ventilator. The patient was administered vancomycin but continued to decline and eventually expired. DISCUSSION: Eggerthella is an anaerobic, gram-positive bacilli present in the gut microflora. Eggerthella infection has most often been reported in intra-abdominal infections. However, cases of bacteremia infection remain sparse. Most infections have been associated with other gastrointestinal processes including Crohn's disease, ulcerative colitis, appendicitis, and diverticulitis abscesses. Our case involved a patient with no significant gastrointestinal history admitted for COVID-19 pneumonia infection on baricitinib complicated by bowel perforation and bacteremia. Bowel perforation is a known risk factor of baricitinib use, and these risks should be discussed with the patient before beginning therapy. Overall mortality for Eggerthella species infection remains high, with some estimates as high as 31%. Much remains unknown about the impact on gut microbiome by SARS-CoV-2, however, early research suggests a higher rate of fungal co-infection in patients with COVID-19. As the literature on COVID-19 expands, more and more unusual pathogens such as Eggerthella may be found to contribute to the morbidity and mortality of patients being treated for COVID-19. CONCLUSIONS: Unusual pathogens such as Eggerthella may complicate a patient's hospital course while undergoing treatment for COVID-19. Reference #1: Alejandra Ugarte-Torres, Mark R Gillrie, Thomas P Griener, Deirdre L Church, Eggerthella lenta Bloodstream Infections Are Associated With Increased Mortality Following Empiric Piperacillin-Tazobactam (TZP) Monotherapy: A Population-based Cohort Study, Clinical Infectious Diseases, Volume 67, Issue 2, 15 July 2018. Reference #2: Gardiner BJ, Tai AY, Kotsanas D, et al. Clinical and microbiological characteristics of Eggerthella lenta bacteremia. J Clin Microbiol. 2015. Reference #3: Lau SK, Woo PC, Fung AM, Chan K-M, Woo GK, Yuen K-Y. Anaerobic, non-sporulating, gram-positive bacilli bacteraemia characterized by 16s rrna gene sequencing. Journal of medical microbiology. 2004. DISCLOSURES: No relevant relationships by Kristin Davis No relevant relationships by Charles Peng

5.
Journal of Pediatric Gastroenterology and Nutrition ; 75(Supplement 1):S274-S275, 2022.
Article in English | EMBASE | ID: covidwho-2058494

ABSTRACT

Background: The phenomenon known as "Long Covid," (LC) marked by post-infectious symptoms of a wide variety, and typically not associated with initial infectious severity, has the potential to become a tremendous public health burden as infections continue at a high rate. Variations of LC may impact over 80% of patients, with unclear pathogenesis, although many speculate that persistent viral presence in end-organ tissue may drive local changes. We previously published a case report noting persistent SARS-nCoV-2 activity in the cecum of a patient 3 months after initial infection (Arostegui et al, JPGN Reports, 2022). We have sought to expand that finding by assessing additional patients who have undergone endoscopic evaluation for presence of SARS-nCoV-2 nucleocapsid, seeking to expand our understanding of the clinical effects of persistent infection. Method(s): We identified 6 patients with onset of symptoms in the post-SARS-nCoV-2 window, who had undergone EGD/colonoscopy without histopathological diagnosis. New blank slides were cut and sent for staining at Histowiz inc (Brooklyn, NY), with rabbit monoclonal SARS-CoV-2 nucleocapsid antibody (GTX635686, 1:10,000). Resulting slides underwent blinded pathology review to identify positives. Chart review was completed on patients who were identified as positive, including histopathology data from endoscopy, medical history, presentation, laboratory results and clinical course. Result(s): Including our initial report, we have identified 4 female patients ages 11-16 to date. Viral presence was identified in the duodenum and TI, but only in one patient in the colon (cecum). Patients presented for evaluation of a variety of GI manifestations including chronic abdominal pain (100%), nausea and vomiting (50%), loss of appetite (50%), tenesmus (50%), hematochezia (25%) as well as weight loss (50%). Notably, of the 4 patients identified, only 1 had a known history of confirmed SARS-nCoV-2 infection. Endoscopic findings in the intestine were normal with the exception of edema noted in the cecum of two patients. Mucosal biopsies were also positive for notable (if typically felt to be non-pathologic) lymphoid aggregates in the Colon (75%) as well as in the Terminal Ileum (50%). Clinical information is summarized in Table 1. Conclusion(s): Additional identification of persistent SARS-nCoV-2 presence in patients ranging from 3-18 months after symptom onset demonstrates a high likelihood that persistent viral presence contributes to post-infectious symptoms in many patients. Patients demonstrated "red flag" symptoms like nighttime awakening with pain, weight loss, and elevated inflammatory markers or calprotectin, but symptomatically improved over time and with measures targeted at IBS. Our limited sample size prevents determination of typical location of persistent viral activity, but it is notable that symptoms for colonic vs. SI persistence were clinically consistent, with diarrhea in colonic persistence and early satiety/pain characterizing SI persistence. Most notably, we have identified a tendency for persistent infection to occur, potentially explaining at least a subset of persistent IBS-like symptoms associated with GI LC. Further work is necessary to determine exactly the prevalence of this issue, as well as to characterize the natural history of the clinical course, and possible effective therapies. (Table Presented).

6.
Journal of Pediatric Gastroenterology and Nutrition ; 75(Supplement 1):S120-S121, 2022.
Article in English | EMBASE | ID: covidwho-2057572

ABSTRACT

INTRODUCTION: The rate of pediatric patients diagnosed with Sars Cov 2 has increased since the early stages of the pandemic. Gastrointestinal symptoms have been demonstrated to be relatively common in pediatric COVID-19 patients as well as severe complications like PIMS syndrome because of the expression of ACE II in different areas of the digestive tract which serves as a receptor for their entry and infection in the body. During the last months of the omicron variant wave, we observed some gastrointestinal conditions in pediatric patients days after the resolution of the Sars Cov 2 acute infection period, sparking our interest to execute further research and analysis. OBJECTIVE(S): Describe the presence of functional gastrointestinal disorders as a post-covid infection sequel METHODS: We performed a descriptive, cross-sectional, observational, retrospective study, were we recollected the clinical and epidemiological data from the medical records of pediatric patients with a history of Sars cov-2 infection confirmed with positive PCR or antigen (sars cov-2) tests at Hospital Angeles Lomas, Mexico City. We included children from 6 months up to 16 years of age, who presented functional gastrointestinal disorders at a minimum 15 days after the infection that fulfilled Rome IV criteria. We evaluated the frequency and proportion of the qualitative variables;we obtained the arithmetic mean and the standard deviation for the quantitative variables with normal distribution RESULTS: We included data from 30 patients with confirmed covid 19 diseases by positive pcr or antigen (sars cov-2) tests, with a mean age 5.327 +/- 3.8 years Min: 7 months Max: 16 years, with a female predominance of 56.7% vs 43% male patients. During the acute infection by covid, 20% presented respiratory symptoms, 13.3% gastrointestinal symptoms, 36.7% only fever, 3.3% dysgeusia and 26.7% were asymptomatic. Adequate nutritional status was detected in 93% of the patients. The mean days the patients presented manifestations was 32 +/- 14 days, at a minimum 15 days, with a maximum of 63 days, being the most frequent functional gastrointestinal disorders: abdominal pain 90%, bloating 76%, vomit and reflux 33%, diarrhea 30%, constipation 26.7%. There was no weight loss in the patients, the appropriate treatment was given for each case. There was no complication in 90% of the patients, 10% presented acute abdominal pain and were transferred to the emergency room, 1 patient was diagnosed with appendicitis and 2 patients with mesenteric lymphadenitis. CONCLUSION Special attention must be paid to toddler and preschooler patients with Sars Cov 2 infection, regardless of the clinical manifestation in acute infections, mild or asymptomatic, functional gastrointestinal disorders may occur in the first 2 months after a positive PCR test. The ileum and the colon are places in which there is a greater expression of the ACE II, so when the enterocytes are invaded by SARS CoV-2, they may produce alterations in absorption and other mechanisms that could be the cause of these consequences. It is of vital importance that all pediatricians are aware of the consequences of the disease to prevent misdiagnosis.

7.
Bangladesh Journal of Medical Science ; 21(4):808-812, 2022.
Article in English | EMBASE | ID: covidwho-2043415

ABSTRACT

Introduction: Angiotensin converting enzyme 2 (ACE2) is expressed in several cell types in the body including the gastrointestinal (GI) epithelium. Objective:To provide an overview of the normal distribution of ACE2 in the GI tract, altered ACE2 expression notably in coronavirus infection and its consequences. Materials and Methods: Pubmed and google scholar were searched using the key words ACE2 paired with GI tract, intestinal permeabilty, gut microbiota, inflammatory bowel disease. Results and Discussion: ACE2 is highly expressed in the ileum and colon in human being as well as in rodents. In this current situation of COVID-19 pandemic, downregulation of ACE2 has been reported due to internalization of the ACE2-virus complex within the cells. Although researches are still in infancy in this topic, altered luminal microbiota, increased intestinal permeability, higher level of inflammatory markers and deficient nutrient transport has been reported due to altered ACE2 expression. Conclusion:Altered expression of ACE2 has the possibility to hamper normal physiological function of the GI tract and might affect GI disease progression and prognosis.

8.
Journal of the Canadian Association of Gastroenterology ; 4, 2021.
Article in English | EMBASE | ID: covidwho-2032052

ABSTRACT

Background: Leflunomide is an oral disease-modifying antirheumatic drug (DMARD), with anti-inflammatory and immunomodulatory properties that has been in use since 1998. Common leflunomide side-effects include gastrointestinal symptoms (nausea, abdominal pain and diarrhea), occurring in 10-20% of patients treated with leflunomide. Scarce evidence exists that leflunomide can cause colitis. Aims: We present the case of a 61-year-old female, with Lupus Erythematosus who presented with colitis induced by long-term leflunomide treatment. Methods: Case report and review of literature Results: A 61-year-old female was seen by the gastroenterology team with complaints of diarrhea ongoing for 6 weeks associated with 10 lb weight loss. The patient had a complex medical history, including lupus, hypothyroidism, asthma, atrial fibrillation, recurrent C. difficile infection, Bell's palsy and avascular necrosis secondary to long-term corticosteroid therapy. Previous immunosuppressive therapies included prednisone, mycophenolic acid (Myfortic), hydroxychloroquine, azathioprine, mycophenolate (CellCept) but due to multiple intolerances, she was initiated on leflunomide in 2014 and has been maintained on it since. Stool analysis ruled out infectious causes. COVID-19 testing was also negative. A CT of the abdomen revealed pancolitis. This was confirmed on colonoscopy, which revealed mild, Mayo 1 pancolitis and normal terminal ileum. She was initiated on Mezavant as a treatment for possible ulcerative colitis. However, during the hospitalization her symptoms, worsened and bloody diarrhea was noted. She underwent a subsequent endoscopic evaluation which revealed more severe disease, Mayo 2-3 colitis, with mucosal hyperemia and ulcerations, as well as effacement of the vasculature. Initial pathology results revealed mild colitis, but repeat pathology results revealed moderate active colitis, with cryptitis, crypt abscesses and significant apoptosis consistent with drug-induced colitis. Given these findings, the diagnosis of leflunomide-induced colitis was made. Leflunomide was therefore discontinued, the patient was initiated on a higher dose of corticosteroids and cholestyramine was initiated. Following these measures, her diarrhea resolved. Conclusions: Leflunomide may cause diarrhea in up to 33% of patients. Challenges related to the diagnosis of leflunomide-induced colitis exist, including the rarity of the diagnosis, a not completely understood mechanism for acute leflunomide-induced diarrhea, as well as variable endoscopic and histologic findings associated with the diagnosis. This report illustrates a case of leflunomide-induced colitis which should be considered in patients on leflunomide, who present with symptoms of abdominal pain and diarrhea, even years after medication initiation.

9.
Journal of the Canadian Association of Gastroenterology ; 4, 2021.
Article in English | EMBASE | ID: covidwho-2030670

ABSTRACT

The proceedings contain 243 papers. The topics discussed include: KRT15+ tumor cells as putative cancer stem cells in esophageal cancer;the circadian timing of inflammatory bowel disease;GM-CSF autoantibodies: predictors of Crohn's disease development and a novel therapeutic approach;an INULIN-type Fructan enriched exclusive enteral nutrition formula modulates the gut microbiome and promotes expansion of anti-inflammatory T cell subsets to suppress colitis;dietary tryptophan modulates kynurenine and indole production in healthy individuals;dorsal root ganglia neuronal responses and substance p production are higher in male mice;food antigen-stress interaction leads to increase pain signaling in ileum and colon via STAT6 in an IBS model;risk perception and knowledge of COVID-19 in patients with celiac disease;pre-treatment HLADQA1-hladrb1 testing for the prevention of azathioprine-induced pancreatitis in inflammatory bowel disease: a prospective cohort study;and a high salt diet synergizes with UC microbiota to induce a proinflammatory immune tone in immunocompetent gnotobiotic mice.

10.
Acta Veterinaria et Zootechnica Sinica ; 53(7):2260-2267, 2022.
Article in Chinese | CAB Abstracts | ID: covidwho-2025546

ABSTRACT

The C-terminal domain (CTD) of porcine deltacoronavirus S1 subunit is the main region which induces the neutralizing antibody. S1-CTD was expressed by HEK-293T eukaryotic expression system and purified, and porcine ileal epithelium cells membrane proteins were extracted to investigate porcine host proteins that interact with it. Thirty-two suspected interacting host proteins were obtained by co-inmunprecipitation (Co-IP) and mass spectrometry. Eukaryotic expression plasmid of KIF1 binding protein (KIFBP) was constructed, and the interaction between KIFBP and S1-CTD was identified by Co-IP and laser confocal microscopy. All results proved that KIFBP interacted with S1-CTD and co-located in cytoplasm. Further research indicated that overexpression of KIFBP could effectively reduce the viral mRNA level and the viral titer in which the mRNA level decreased by about 70%, and the viral titer decreased by 101.6TCID50. In conclusion, a host protein KIFBP interacting with PDCoV S1-CTD was screened and identified in this study which provides a theoretical basis for understanding the pathogenesis of PDCoV.

11.
Pediatrics ; 149, 2022.
Article in English | EMBASE | ID: covidwho-2003370

ABSTRACT

Introduction: Abdominal pain is one of the most common complaints seen in the pediatric acute care setting. SARS-CoV-2 disease in children includes a hyperinflammatory syndrome called Multisystem Inflammatory Syndrome in Children (MIS-C). Gastrointestinal symptoms are most common in pediatric acute SARS-CoV-2 infection as well as in MIS-C. Case Description: A 13- year-old female presented with diffuse lower abdominal pain for 3-days. Pain was 10/10 in intensity, worsened with movement, and had associated constipation, anorexia, nausea, and vomiting. Exam showed an ill-appearing female with labile vitals and generalized lower abdominal tenderness with good bowel sounds. Ultrasound suggested features of acute appendicitis but a follow-up CT did not visualize the appendix. She was admitted to the inpatient unit after routine screening revealed positive SARS-CoV-2 antibody but negative PCR. She received IV fluid bolus, narcotic analgesics, and ampicillin-sulbactam preoperatively. Within hours, she spiked high-grade fevers (101.4F), sustained hypotension, and tachycardia with concern for sepsis secondary to a possible ruptured appendix. She underwent emergency diagnostic laparoscopy which revealed bile-tinged fluid in the lower quadrant, a mildly inflamed appendicular tip without perforation, and thickened mesenteric nodes within the inflamed distal ileum. Intra-operatively, she had persistent hypotension requiring fluid boluses and vasopressors. Her admission labs revealed elevated inflammatory markers, deranged coagulation profile, and elevated cardiac enzymes. Her differential diagnosis was then revised to include MIS-C and severe sepsis. Antibiotic coverage was broadened to Vancomycin and Meropenem. An Echocardiogram showed mitral regurgitation with moderately to severely decreased right and left ventricular systolic dysfunction with an ejection fraction of 32.8% The patient was then transferred to the pediatric cardiac critical unit where she received treatment with IVIG, steroids, and anticoagulants. Her clinical status and lab studies improved with EF > 50%. She was discharged from the intensive care unit after 7 days and has had an uneventful follow-up. Discussion: Differential diagnosis for acute lower abdominal pain in an adolescent female is broad. Similar cases with predominant GI symptoms and later generalized multisystem involvement have been reported, however, most were managed conservatively. Two reports have been published on MIS-C presenting as acute appendicitis, but neither had significant cardiac involvement. Our patient's presentation can easily be confused with an acute surgical abdomen but the pathology report confirmed a congested appendix without any fecoliths supporting either inflammation or vasculitis as the cause for her presentation, which is in concordance with the hyperinflammatory state that has previously been described in patients presenting with a history of past SARS-CoV- 2 infections. Conclusion: MIS-C can mimic serious pediatric illnesses including sepsis, acute abdomen, and Kawasaki disease. Clinicians should have a low threshold for suspecting MIS-C, as prompt treatment can be lifesaving. Universal screening for COVID-19 infection with PCR and antibody tests can expedite the diagnostic evaluation of severely ill children. Showing reactive wall thickening of the cecum and small bowel loops (red arrow) and enlarged mesenteric lymph nodes (yellow arrow). The appendix could not be visualized here.

12.
Gastroenterology ; 162(7):S-887, 2022.
Article in English | EMBASE | ID: covidwho-1967383

ABSTRACT

Background: ACE2 is a carboxypeptidase homolog to the dipeptidase ACE but with different substrate specificity;while ACE principally acts as a carboxydipeptidase (peptidyldipeptidase) removing the C-terminal dipeptide from Ang I to form Ang II, ACE2 functions exclusively as a carboxypeptidase removing a single C-terminal amino acid from Ang II generating Ang- (1-7) or, much less efficiently, from Ang I forming Ang-(1-9). ACE and ACE2 than playing a key role in regulating the renin–angiotensin–aldosterone system (RAAS). In the normal lung, ACE2 mRNA is mainly expressed by type II alveolar epithelial cells and endothelial cells, but the level of expression increases in response to inflammation while is downregulated in response to SARS-CoV infection. ACE2, mRNA and protein, is highly expressed in the gastrointestinal tract, with the higher expression detected in epithelial cells of the ileum and the colon where mediates the absorption of amino acids. ACE2 expression in the intestine undergoes regulation in response to a variety of factors including intestinal microbiota and inflammation. Furthermore, previous studies have suggested that insulinotropic factor glucagon like peptide (GLP)-1 might regulate ACE2 expression in the heart, suggesting a potential interaction of GLP1 with ACE2. GPBAR1, G Protein Bile Acid Receptor, is robustly expressed in the gastrointestinal tract and its activation in the intestine promotes the release of GLP-1. Aim: to investigate the possible interaction between bile acids via GPBAR1 and the expression of ACE2 in the gastrointestinal tract. Materials and Methods: HT29 cells treated with TNF-α + IL-1β and mouse models of colitis were used to assess ACE2 expression and treatment with BAR501, a GPBAR1 agonist, was used to investigate its modulation. Results: The inflammatory stimulus increased the expression of Ace2 in HT29 cells and in colon of mice according to the data obtained in human samples from patient with IBD. GPBAR1 agonism by BAR501 relieved inflammation both in vitro and in vivo but in vitro this effect induced down-regulation of ACE2 while in vivo administration of BAR501 increased ACE2 expression. In mouse model of colitis, inflammation up-regulated also the GLP-1 gene expression that was further increased by BAR501 and instead, the administration of Exendina- 3, a GLP-1R antagonist was able to block the up-regulation of Ace2 expression exerted by BAR501. Conclusions: In conclusion, our results demonstrate that both in vivo and in vitro activation of GPBAR1 by a selective agonist exerts an anti-inflammatory effect. On the other hand, in vivo activation of GPBAR1 in the colon induces the release of GLP-1, which mediates some of the anti-inflammatory effects exerted by the receptor, and induces further upregulation of Ace2 by GPBAR1/GLP-1/GLP-1R axis.(Figure Presented)

13.
Gastroenterology ; 162(7):S-277, 2022.
Article in English | EMBASE | ID: covidwho-1967262

ABSTRACT

Background: Although respiratory failure is the hallmark of severe disease, it is increasingly clear that Coronavirus Disease 2019 (COVID-19) is a multi-system disorder. The presence of gastrointestinal (GI) involvement by Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been suggested by epidemiological, clinical, non-human primate, in-vitro (enteroid) and ex-vivo (human biopsy) studies. Having recently documented persistence of SARS-CoV-2 within the intestinal epithelium 7 months after infection, here we aimed to study mucosal immune cell abnormalities in individuals with prior history of COVID-19. Methods: Individuals with previous COVID-19 diagnosis (by either RT–PCR or seroconversion) and controls (without RT-PCR or serological evidence of prior COVID-19 infection) undergoing endoscopic evaluation were recruited into the study (Table 1). Colonic and small intestinal (duodenal and ileal) biopsies were analyzed by multiparameter flow cytometry for mucosal immune cell populations including myeloid cells (classical and non-classical monocytes, dendritic cell subsets), T cells (subsets and activation state), B cells (including plasma cells) and NK cells. Persistence of viral antigens was determined by immunofluorescence microscopy (n=30) using a previously published anti-nucleocapsid (NP) antibody. Results: Thirty subjects with a previous history of COVID-19 (post-COVID), median of 4 months from diagnosis (range 1-10 months), were recruited and compared with 40 normal volunteer (NV) controls. Relative to controls, post-COVID subjects displayed higher frequencies of classical (CD14+) monocytes in both, the colon and the small bowel, while significantly higher frequencies of conventional dendritic cells (cDC)1 (lin-HLA-DRhiCD14- CD11c+CD141+) and cDC2 (lin-HLA-DRhiCD14-CD11c+CD1c+) were noted in the colon. Among NK subsets, CD56bright CD16- NK cells were significantly higher in the colon of post-COVID subjects. Among T cell subsets, CD8+ tissue resident memory T cells (CD8+CD69+CD103+) were significantly increased in colon of post-COVID subjects compared to NV. Among B cell subsets, plasma cells (CD3-CD27+CD38hi) trended higher (p= 0.06), while mucosal B cells (CD3-CD19+) were significantly lower in the terminal ileum of post-COVID subjects compared to NV. Finally, with IF, we detected SARS-CoV-2 NP in 10 out of 30 (33%) of post-COVID subjects (Figure 1). Conclusion: Innate and adaptive immune cell abnormalities persist in the intestinal mucosa of post-COVID subjects for up to 10 months and may reflect viral persistence or immune cell dysregulation in the intestines. These findings have major implications for understanding the pathogenesis of long-term sequelae of COVID-19, including long-haul COVID.(Table Presented)(Figure Presented)

14.
Gastroenterology ; 162(7):S-159, 2022.
Article in English | EMBASE | ID: covidwho-1967248

ABSTRACT

Objective: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been detected in multiple organ systems including the gastrointestinal (GI) tract using standard PCR techniques. However, whether the human gut supports active SARS-CoV-2 replication leading to shedding of infectious virions is still a matter of debate. Our study aimed to determine whether SARS-CoV-2 could be recovered from the GI tract of asymptomatic outpatients to assess the risk of SARS-CoV-2 exposure for healthcare workers performing routine endoscopies. Methods: Between April 2020 and February 2021, we enrolled 112 patients aged 19 – 70 years undergoing elective endoscopic procedures who had no known SARS-CoV-2 exposure or recent COVID-19 test result (n=100) or who had a history of previous SARS-CoV-2 infection but had recovered at the time of the procedure (n=12). None of the patients had gastrointestinal symptoms at the time of COVID-19 infection or respiratory complaints at the time of the endoscopy. Liquids and biopsies from the colon, ileum, duodenum, and stomach were collected during endoscopy following standard bowel preparation protocols. Samples were analyzed for SARS-CoV-2 by PCR, and PCR-positive samples were analyzed for the presence of infectious virus by VeroE6 plaque assays. We also used plaque assays to assess whether endoscopic colonic liquids could inactivate SARSCoV- 2. Results: Interestingly, one colonic biopsy out of the 255 tissue samples collected from patients with no known SARS-CoV-2 exposure tested positive for SARS-CoV-2 by PCR. Out of 12 patients who had recovered from COVID-19 between 2 and 21 weeks before the endoscopic procedure, three colonic fluid samples tested positive for SARS-CoV-2 (Fig. 1A). Positive PCR results were confirmed by an independent laboratory. Importantly, no replication-competent virus was detected in any of the tissue or liquid samples. In vitro treatment of SARS-CoV-2 with colonic liquid showed that SARS-CoV-2 was completely inactivated after 24 hours, but at 10 minutes and 1-hour viral inactivation varied considerably between samples (Fig. 1B). Discussion: In 25% (3 out of 12) of patients with previous COVID-19 history, virus was detected by PCR for up to 5 months following resolution of symptoms. Viral genomes were also detected in colonic biopsies from one subject with no known SARS-CoV-2 infection, consistent with a large proportion of asymptomatic infections in the US population. The persistent detection of SARS-CoV-2 genomes in endoscopy samples after resolution of COVID-19 points to the gut as a reservoir for SARS-CoV-2 and confirms previous reports of long-term SARS-CoV-2 shedding in fecal samples. However, the absence of infectious virions in the samples and the rapid inactivation of SARS-CoV-2 in colon liquids suggests that the risk to healthcare workers involved in endoscopy procedures is likely low. (Figure Presented)

15.
Diseases of the Colon and Rectum ; 65(5):157-158, 2022.
Article in English | EMBASE | ID: covidwho-1894036

ABSTRACT

Purpose/Background: Although GI melanoma is commonly a metastatic disease, it is very unusual to see the mesenteric mass of the cecum and terminal ileum as the primary origin of melanoma. Hypothesis/Aim: This is a case report and presentation showing a rare occasion of primary melanoma in the cecum and the terminal ileum mesentery along the ileocolic pedicle causing cecal complete bowel obstruction. Methods/Interventions: The reported case is a rare occasion of large bowel obstruction near the cecum resulted from primary mesenteric melanoma invading into the wall of the descending colon. Primary melanoma of the GI tract is still controversial and only a limited of cases have been reported in the literature. We added a review of the other published case reports to this case report using Endnote. Results/Outcome(s): This is a 68-year-old female who was seen in the outpatient setting with increasing abdominal girth in addition to nausea and vomiting and obstipation. The patient had alternating bowel habits for over 2 months which she felt this was related to Covid as she was tested Covid positive and diagnosed with Covid pneumonia at the same time. She was directly admitted from the office to the inpatient and she had a CAT scan of the abdomen pelvis that demonstrated cecal obstruction related to possibly cecal mass/mesenteric mass with multiple liver metastatic diseases. She underwent exploratory laparotomy which resulted in Right extended hemicolectomy en bloc with a loop of jejunum and part of the terminal ileum. We tested later serum S100 the protein and it was elevated to 18,000, she had serum negative alpha-fetoprotein and negative CEA. This is a 68-year-old female who was seen in the outpatient setting with increasing abdominal girth in addition to nausea and vomiting and obstipation. The patient had alternating bowel habits for over 2 months which she felt was related to Covid as she was tested Covid positive and diagnosed with Covid pneumonia at the same time. She was directly admitted from the office to the inpatient service and she had a CAT scan of the abdomen pelvis that demonstrated cecal obstruction related to possibly cecal mass/ mesenteric mass with multiple liver metastatic diseases. She underwent exploratory laparotomy which resulted in Right extended hemicolectomy en bloc with a loop of jejunum and part of the terminal ileum. She had also intraoperative liver biopsy that demonstrated metastasis of the melanoma to the liver. We tested later serum S100 the protein and it was elevated to 18,000, she had serum negative alpha-fetoprotein and negative CEA. Limitations: Case report study with reported cases reviewed. Conclusions/Discussion: Large bowel obstruction could be related to unusual diagnoses like melanoma of the bowel mesentery. Although, primary GI melanoma is rare this showed the possibility of such diagnosis. (Figure Presented).

16.
Topics in Antiviral Medicine ; 30(1 SUPPL):75, 2022.
Article in English | EMBASE | ID: covidwho-1880788

ABSTRACT

Background: SARS-CoV-2 infection results in a spectrum of disease severity attributable to the magnitude of the underlying inflammatory response. Aged individuals with co-morbidities are most vulnerable and severely affected, but the mechanisms driving aberrant immune responses fueling SARS-CoV-2 immunopathology in this high-risk population are not fully elucidated. We hypothesized that asymptomatic CMV infection might exacerbate SARS-CoV-2 pathogenesis since its replication is both a cause and consequence of inflammation and appears to worsen oxygenation in critically ill patients (Limaye, JAMA, 2017). CMV-seropositivity was associated with increased hospitalization among people with SARS-CoV-2 infection (Shrock, Science, 2020). To begin to address this hypothesis, we utilized the rhesus macaque model of natural rhesus (Rh)CMV infection to investigate the extent to which SARS-CoV-2 induces CMV reactivation in the anatomic sites of SARS-CoV-2 pathology. Methods: To assess CMV reactivation, eight aged, type 2 diabetic RhCMV-seropositive rhesus macaques (sera anti-CMV IgG: 300-1400 ng/ml) were infected with high-dose SARS-CoV-2 (2.5x10 6 PFU) and monitored for 7 days prior to euthanasia. Samples from the respiratory tract, intestinal tract, and blood were collected to assess viral and inflammatory dynamics in distinct tissue compartments. Results: Following infection, SARS-CoV-2 replication was observed throughout the respiratory tract, which was associated with local and systemic inflammation and immune activation. Lung histopathological assessments revealed development of interstitial pneumonia with colocalization of SARS nucleocapsid protein within pneumocytes. qPCR assays targeting RhCMV gB showed CMV DNA within the caudal lung lobe (up to 103 CMV DNA copies/mg of tissue) in all animals at day 7, and the animal with the highest CMV DNA presented with the most profound clinical symptoms. Strikingly, CMV DNA copies strongly correlated with CD4 and CD8 T cell activation indices in blood and spleen (r = 0.96, p< 0.001). Additionally, we found RhCMV reactivation in the ileum, where high levels of ACE2 are reported. Conclusion: SARS-CoV-2 infection of RhCMV-seropositive macaques results in CMV reactivation in the anatomic sites where SARS-CoV-2 causes pathology. Future experimental studies should address whether CMV reactivation exacerbates SARS-CoV-2 pathogenesis.

17.
Colorectal Disease ; 24(SUPPL 1):143, 2022.
Article in English | EMBASE | ID: covidwho-1745949

ABSTRACT

Background: To investigate the outcome (30-day in-hospital mortality, length of stay and readmission within 28 days) of emergency inflammatory bowel disease (IBD) care in the Covid-19 pandemic. To quantify the reduction in provision of IBD investigations and procedures during the pandemic. Methods: Nationwide observational study using administrative data (Hospital Episode Statistics) for England (2015-2020). Autoregressive integrated moving average (ARIMA) forecast models were run to estimate the counterfactual IBD admissions and procedures for February 2020 onwards had the pandemic not occured. Results: Large decreases in attendances to hospital for emergency treatment were noted for both acute ulcerative colitis (UC) and Crohn's disease (CD) (17.4% and 10.3%). The prevalence of concomitant Sars-CoV- 2 infection during the same episode was low for UC and CD [1.7% (247/14,708) and 1.3% (179/14,126), respectively]. All IBD procedures and investigations showed marked decreases in volume to December 2020 compared to the counterfactual estimates. The largest absolute deficits were in lower gastrointestinal endoscopy (16,223, 35.7% reduction), reversal of ileostomy (2,489, 39.7% reduction) and right sided/ileal resection or strictureplasty for Crohn's disease (879, 12.5% reduction). There were no significant clinical differences in case mix or outcome of emergency admission for IBD in the pandemic compared to a historical cohort. Conclusion: There is likely a significant burden of untreated IBD in the community exacerbated by the pandemic based on reductions in emergency IBD care and IBD procedures undertaken in 2020. Patients with IBD may experience significant clinical harm or a protracted decrease in quality of life if care is not prioritised.

18.
Journal of Crohn's and Colitis ; 16:i068-i069, 2022.
Article in English | EMBASE | ID: covidwho-1722297

ABSTRACT

Background: Although respiratory failure is the hallmark of severe disease, it is increasingly clear that Coronavirus Disease 2019 (COVID-19) is a multi-system disorder. The presence of gastrointestinal (Gl) involvement by Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been suggested by epidemiological, clinical, non-human primate, invitro (enteroid) and ex-vivo (human biopsy) studies. Having recently documented persistence of SAR-CoV-2 within the intestinal epithelium 7 months after infection, here we aimed to study mucosal immune cell abnormalities in individuals with prior history of COVID-19. Methods: Individuals with previous COVID-19 diagnosis (by either RT- PCR or seroconversion) and controls (without RT-PCR or serological evidence of prior COVID-19 infection) undergoing endoscopic evaluation were recruited into the study (Table 1,2). Colonic and small intestinal (duodenal and ileal) biopsies were analyzed by multiparameter flow cytometry for mucosal immune cell populations including myeloid cells (classical and non-classical monocytes, dendritic cell subsets), T cells (subsets and activation state), B cells (including plasma cells). Persistence of viral antigens was determined by immunofluorescence microscopy (n=30) using a previously published anti-nucleocapsid (NP) antibody. Results: Thirty subjects with a previous history of COVID-19 (post- COVID), median of 4 months from diagnosis (range 1-10 months), were recruited and compared with 40 normal volunteer (NV) controls. Relative to controls, post-COVID subjects displayed higher frequencies of classical (CD14+) monocytes in both, the colon and the small bowel, while significantly higher frequencies of conventional dendritic cells (cDC) 1 (lin-HLA-DRhiCD14-CD11c+CD141+) and cDC2 (lin-HLA-DRhiCD14-- CD11c+CD1c+) were noted in the colon only. Among T cell subsets, CD8+ tissue resident memory T cells (CD8+CD69+CD103+) were significantly increased in colon of post-COVID subjects compared to NV. Among B cell subsets, plasma cells (CD3-CD27+CD38hi) trended higher (p=0.06), while mucosal B cells (CD3-CD19+) were significantly lower in the terminal ileum of post-COVID subjects compared to NV. Finally, with IF, we detected SARS-CoV-2 NP in 10 out of 30 (33%) of post-COVID subjects (Figure 1). There were no significant correlations of these cell populations with either time after the infection or IF positivity. Conclusion: Innate and adaptive immune cell abnormalities persist in the intestinal mucosa of post-COVID subjects for up to 10 months and may reflect viral persistence or immune cell dysregulation in the intestines. These findings have major implications for understanding the pathogenesis of long term sequela of COVID-19, including long-haul COVID.

SELECTION OF CITATIONS
SEARCH DETAIL