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1.
World J Gastroenterol ; 28(13): 1377-1379, 2022 Apr 07.
Article in English | MEDLINE | ID: covidwho-1855873

ABSTRACT

Gastric cancer is widespread globally, and disease diagnosis is accompanied by high mortality and morbidity rates. However, prognoses and survivability have improved following implementation of surveillance and screening programs, which have led to earlier diagnoses. Indeed, early diagnosis itself supports increased surgical curability, which is the main treatment goal and guides therapeutic choice. The most recent Japanese guidelines for endoscopic submucosal dissection and endoscopic mucosal resection for early gastric cancer consider the degree of endoscopic curability in relation to the characteristics of the gastric lesions. In clinical practice, the management approach for both prevention and treatment should be similar to that of colon lesions; however, unlike the established practices for colorectal cancer, the diagnostic and therapeutic pathways are not shared nor widespread for gastric cancer. Ultimately, this negatively impacts the opportunity to perform an endoscopic resection with curative intent.


Subject(s)
Endoscopic Mucosal Resection , Stomach Neoplasms , Endoscopy , Gastric Mucosa/pathology , Humans , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery
2.
FEBS Lett ; 595(17): 2257-2270, 2021 09.
Article in English | MEDLINE | ID: covidwho-1439663

ABSTRACT

HIV preferentially infects α4 ß7 + CD4 T cells, forming latent reservoirs that contribute to HIV persistence during antiretroviral therapy. However, the properties of α4 ß7 + CD4 T cells in blood and mucosal compartments remain understudied. Employing two distinct models of HIV infection, HIV-infected humans and simian-human immunodeficiency virus (SHIV)-infected rhesus macaques, we show that α4 ß7 + CD4 T cells in blood are enriched for genes regulating cell cycle progression and cellular metabolism. Unlike their circulating counterparts, rectal α4 ß7 + CD4 T cells exhibited a core tissue-residency gene expression program. These features were conserved across primate species, indicating that the environment influences memory T-cell transcriptional networks. Our findings provide an important molecular foundation for understanding the role of α4 ß7 in HIV infection.


Subject(s)
CD4-Positive T-Lymphocytes/metabolism , CD4-Positive T-Lymphocytes/virology , HIV Infections/blood , Integrins/metabolism , Adult , Animals , COVID-19/blood , COVID-19/virology , Cell Cycle , Cell Proliferation , Gastric Mucosa/cytology , Gastric Mucosa/virology , Gene Expression Regulation , Humans , Immunization , Macaca mulatta , Male , Simian Acquired Immunodeficiency Syndrome/blood , Simian Acquired Immunodeficiency Syndrome/virology
3.
BMJ Open Gastroenterol ; 8(1)2021 02.
Article in English | MEDLINE | ID: covidwho-1102175

ABSTRACT

BACKGROUND: Although evidence suggests frequent gastrointestinal (GI) involvement during coronavirus disease 2019 (COVID-19), endoscopic findings are scarcely reported. AIMS: We aimed at registering endoscopic abnormalities and potentially associated risk factors among patients with COVID-19. METHODS: All consecutive patients with COVID-19 undergoing endoscopy in 16 institutions from high-prevalence regions were enrolled. Mann-Whitney U, χ2 or Fisher's exact test were used to compare patients with major abnormalities to those with negative procedures, and multivariate logistic regression to identify independent predictors. RESULTS: Between February and May 2020, during the first pandemic outbreak with severely restricted endoscopy activity, 114 endoscopies on 106 patients with COVID-19 were performed in 16 institutions (men=70.8%, median age=68 (58-74); 33% admitted in intensive care unit; 44.4% reporting GI symptoms). 66.7% endoscopies were urgent, mainly for overt GI bleeding. 52 (45.6%) patients had major abnormalities, whereas 13 bled from previous conditions. The most prevalent upper GI abnormalities were ulcers (25.3%), erosive/ulcerative gastro-duodenopathy (16.1%) and petechial/haemorrhagic gastropathy (9.2%). Among lower GI endoscopies, 33.3% showed an ischaemic-like colitis.Receiver operating curve analysis identified D-dimers >1850 ng/mL as predicting major abnormalities. Only D-dimers >1850 ng/mL (OR=12.12 (1.69-86.87)) and presence of GI symptoms (OR=6.17 (1.13-33.67)) were independently associated with major abnormalities at multivariate analysis. CONCLUSION: In this highly selected cohort of hospitalised patients with COVID-19 requiring endoscopy, almost half showed acute mucosal injuries and more than one-third of lower GI endoscopies had features of ischaemic colitis. Among the hospitalisation-related and patient-related variables evaluated in this study, D-dimers above 1850 ng/mL was the most useful at predicting major mucosal abnormalities at endoscopy. TRIAL REGISTRATION NUMBER: ClinicalTrial.gov (ID: NCT04318366).


Subject(s)
COVID-19/pathology , Endoscopy, Gastrointestinal , Gastric Mucosa/pathology , Aged , COVID-19/complications , Colitis, Ischemic/etiology , Colitis, Ischemic/pathology , Cross-Sectional Studies , Duodenum/pathology , Female , Gastrointestinal Hemorrhage/etiology , Gastrointestinal Hemorrhage/pathology , Humans , Male , Middle Aged , Pandemics , Prospective Studies , Risk Factors , SARS-CoV-2 , Stomach Ulcer/etiology , Stomach Ulcer/pathology
4.
Gastroenterology ; 160(5): 1647-1661, 2021 04.
Article in English | MEDLINE | ID: covidwho-1065985

ABSTRACT

BACKGROUND & AIMS: Gastrointestinal (GI) manifestations have been increasingly reported in patients with coronavirus disease 2019 (COVID-19). However, the roles of the GI tract in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are not fully understood. We investigated how the GI tract is involved in SARS-CoV-2 infection to elucidate the pathogenesis of COVID-19. METHODS: Our previously established nonhuman primate (NHP) model of COVID-19 was modified in this study to test our hypothesis. Rhesus monkeys were infected with an intragastric or intranasal challenge with SARS-CoV-2. Clinical signs were recorded after infection. Viral genomic RNA was quantified by quantitative reverse transcription polymerase chain reaction. Host responses to SARS-CoV-2 infection were evaluated by examining inflammatory cytokines, macrophages, histopathology, and mucin barrier integrity. RESULTS: Intranasal inoculation with SARS-CoV-2 led to infections and pathologic changes not only in respiratory tissues but also in digestive tissues. Expectedly, intragastric inoculation with SARS-CoV-2 resulted in the productive infection of digestive tissues and inflammation in both the lung and digestive tissues. Inflammatory cytokines were induced by both types of inoculation with SARS-CoV-2, consistent with the increased expression of CD68. Immunohistochemistry and Alcian blue/periodic acid-Schiff staining showed decreased Ki67, increased cleaved caspase 3, and decreased numbers of mucin-containing goblet cells, suggesting that the inflammation induced by these 2 types of inoculation with SARS-CoV-2 impaired the GI barrier and caused severe infections. CONCLUSIONS: Both intranasal and intragastric inoculation with SARS-CoV-2 caused pneumonia and GI dysfunction in our rhesus monkey model. Inflammatory cytokines are possible connections for the pathogenesis of SARS-CoV-2 between the respiratory and digestive systems.


Subject(s)
COVID-19/transmission , Gastroenteritis/pathology , Gastrointestinal Tract/pathology , Lung/pathology , Animals , Bronchi/metabolism , Bronchi/pathology , COVID-19/immunology , COVID-19/metabolism , COVID-19/pathology , COVID-19 Nucleic Acid Testing , Caspase 3/metabolism , Cytokines/immunology , Disease Models, Animal , Gastric Mucosa , Gastroenteritis/metabolism , Gastroenteritis/virology , Gastrointestinal Tract/immunology , Gastrointestinal Tract/metabolism , Goblet Cells/pathology , Intestine, Small/metabolism , Intestine, Small/pathology , Ki-67 Antigen/metabolism , Lung/diagnostic imaging , Lung/immunology , Lung/metabolism , Macaca mulatta , Nasal Mucosa , RNA, Viral/isolation & purification , Random Allocation , Rectum/metabolism , Rectum/pathology , SARS-CoV-2 , Trachea/metabolism , Trachea/pathology
5.
Steroids ; 165: 108759, 2021 01.
Article in English | MEDLINE | ID: covidwho-917434

ABSTRACT

Gastric ulcers are a very common public health problem affecting up to 10% worldwide. Russelioside B is a steroidal glycoside isolated from several Caralluma species. No study tested the ulcer healing potential of the compound. The current study aimed to assess the protective effect of russelioside B against ethanol-induced gastric mucosal injury in rats. Ulcer was induced on rats by a single intragastric dose of absolute ethanol (5 mL/kg). Rats were randomly assorted into four groups (n = 8) and given treatments (Antodine, 20 mg/kg or russelioside B, 50 mg/kg) by oral gavage 1 h before ulcer induction. Pretreatment with russelioside B (50 mg/kg) attenuated the gastric mucosal injury as proved by a decrease of ulcer index, and histological scores. It suppressed the gastric inflammation by a significant lowering the tumor necrosis factor-α and interleukin-6 levels with myeloperoxidase activity (which are also aggravating factors in the case of Covid-19 infection). In addition, administration of russelioside B halted the gastric oxidative stress via inhibition of lipid peroxides by maintaining reduced glutathione and by decreasing malondialdehyde. It was able also to restore the sharp drop in the levels of heat shock protein-70, vascular endothelial growth factor and prostaglandin E2 induced by ethanol. Additionally, it showed carbonic anhydrase inhibition activity. The gastroprotective action of russelioside B was umpired through multi mechanistic actions; suppression of gastric oxidative stress, inflammation, anti-apoptotic activities and enhanced gastric mucosal protection by up-regulation of endothelial growth factor, normalization of heat shock protein-70 and prostaglandin E2. These actions were comparable in part to some classical antiulcer drugs such as Antodine.


Subject(s)
Dinoprostone/genetics , Glycosides/pharmacology , HSP70 Heat-Shock Proteins/genetics , Pregnanes/pharmacology , Stomach Ulcer/drug therapy , Animals , Anti-Ulcer Agents/pharmacology , Apocynaceae/chemistry , COVID-19/drug therapy , COVID-19/genetics , COVID-19/virology , Disease Models, Animal , Ethanol/toxicity , Gastric Mucosa/drug effects , Gastric Mucosa/pathology , Gene Expression Regulation/drug effects , Glycosides/chemistry , Humans , Interleukin-6/genetics , Oxidative Stress/drug effects , Peroxidase/genetics , Pregnanes/chemistry , Rats , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Stomach Ulcer/chemically induced , Stomach Ulcer/genetics , Stomach Ulcer/pathology , Tumor Necrosis Factor-alpha/genetics
7.
Am J Gastroenterol ; 115(10): 1707-1715, 2020 10.
Article in English | MEDLINE | ID: covidwho-732653

ABSTRACT

INTRODUCTION: Proton pump inhibitors (PPIs) increase the risk for enteric infections that is likely related to PPI-induced hypochlorhydria. Although the impact of acid suppression on severe acute respiratory syndrome coronavirus 2 is unknown thus far, previous data revealed that pH ≤3 impairs the infectivity of the similar severe acute respiratory syndrome coronavirus 1. Thus, we aimed to determine whether use of PPIs increases the odds for acquiring coronavirus disease 2019 (COVID-19) among community-dwelling Americans. METHODS: From May 3 to June 24, 2020, we performed an online survey described to participating adults as a "national health survey." A multivariable logistic regression was performed on reporting a positive COVID-19 test to adjust for a wide range of confounding factors and to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS: Of 53,130 participants, 3,386 (6.4%) reported a positive COVID-19 test. In regression analysis, individuals using PPIs up to once daily (aOR 2.15; 95% CI, 1.90-2.44) or twice daily (aOR 3.67; 95% CI, 2.93-4.60) had significantly increased odds for reporting a positive COVID-19 test when compared with those not taking PPIs. Individuals taking histamine-2 receptor antagonists were not at elevated risk. DISCUSSION: We found evidence of an independent, dose-response relationship between the use of antisecretory medications and COVID-19 positivity; individuals taking PPIs twice daily have higher odds for reporting a positive test when compared with those using lower-dose PPIs up to once daily, and those taking the less potent histamine-2 receptor antagonists are not at increased risk. These findings emphasize good clinical practice that PPIs should only be used when indicated at the lowest effective dose, such as the approved once-daily label dosage of over-the-counter and prescription PPIs. Further studies examining the association between PPIs and COVID-19 are needed.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/epidemiology , Gastric Acid/metabolism , Health Surveys/statistics & numerical data , Pneumonia, Viral/epidemiology , Proton Pump Inhibitors/adverse effects , Adolescent , Adult , Betacoronavirus/isolation & purification , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques/statistics & numerical data , Confounding Factors, Epidemiologic , Coronavirus Infections/diagnosis , Coronavirus Infections/physiopathology , Coronavirus Infections/virology , Drug Prescriptions/statistics & numerical data , Female , Gastric Mucosa/drug effects , Gastric Mucosa/metabolism , Gastroesophageal Reflux/drug therapy , Gastrointestinal Microbiome/drug effects , Gastrointestinal Microbiome/physiology , Heartburn/drug therapy , Humans , Hydrogen-Ion Concentration/drug effects , Middle Aged , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/physiopathology , Pneumonia, Viral/virology , SARS-CoV-2 , Young Adult
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