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World Journal of Gastroenterology Dec 2023The etiology of upper gastrointestinal bleeding (UGIB) varies by age, from newborns to adolescents, with some of the causes overlapping between age groups. While... (Review)
Review
The etiology of upper gastrointestinal bleeding (UGIB) varies by age, from newborns to adolescents, with some of the causes overlapping between age groups. While particular causes such as vitamin K deficiency and cow's milk protein allergy are limited to specific age groups, occurring only in neonates and infants, others such as erosive esophagitis and gastritis may be identified at all ages. Furthermore, the incidence of UGIB is variable throughout the world and in different hospital settings. In North America and Europe, most UGIBs are non-variceal, associated with erosive esophagitis, gastritis, and gastric and duodenal ulcers. In recent years, the most common causes in some Middle Eastern and Far Eastern countries are becoming similar to those in Western countries. However, variceal bleeding still predominates in certain parts of the world, especially in South Asia. The most severe hemorrhage arises from variceal bleeding, peptic ulceration, and disseminated intravascular coagulation. Hematemesis is a credible indicator of a UGI source of bleeding in the majority of patients. Being familiar with the most likely UGIB causes in specific ages and geographic areas is especially important for adequate orientation in clinical settings, the use of proper diagnostic tests, and rapid initiation of the therapy. The fundamental approach to the management of UGIB includes an immediate assessment of severity, detecting possible causes, and providing hemodynamic stability, followed by early endoscopy. Unusual UGIB causes must always be considered when establishing a diagnosis in the pediatric population because some of them are unique to children. Endoscopic techniques are of significant diagnostic value, and combined with medicaments, may be used for the management of acute bleeding. Finally, surgical treatment is reserved for the most severe bleeding.
Topics: Child; Infant, Newborn; Adolescent; Animals; Cattle; Female; Infant; Humans; Gastrointestinal Hemorrhage; Esophageal and Gastric Varices; Peptic Ulcer; Esophagitis; Gastritis; Age Factors
PubMed: 38186684
DOI: 10.3748/wjg.v29.i47.6095 -
Physiological Reports Feb 2021Obesity is associated with the development of insulin resistance (IR) and type-2 diabetes mellitus (T2DM); however, not all patients with T2DM are obese. The... (Comparative Study)
Comparative Study
BACKGROUND
Obesity is associated with the development of insulin resistance (IR) and type-2 diabetes mellitus (T2DM); however, not all patients with T2DM are obese. The Goto-Kakizaki (GK) rat is an experimental model of spontaneous and non-obese T2DM. There is evidence that the intestine contributes to IR development in GK animals. This information prompted us to investigate small intestine remodeling in this animal model.
METHODS
Four-month-old male Wistar (control) and GK rats were utilized for the present study. After removing the small intestine, the duodenum, proximal jejunum, and distal ileum were separated. We then measured villi and muscular and mucosa layer histomorphometry, goblet cells abundance, total myenteric and submucosal neuron populations, and inflammatory marker expression in the small intestinal segments and intestinal transit of both groups of animals.
KEY RESULTS
We found that the GK rats exhibited decreased intestinal area (p < 0.0001), decreased crypt depth in the duodenum (p = 0.01) and ileum (p < 0.0001), increased crypt depth in the jejunum (p < 0.0001), longer villi in the jejunum and ileum (p < 0.0001), thicker villi in the duodenum (p < 0.01) and ileum (p < 0.0001), thicker muscular layers in the duodenum, jejunum, and ileum (p < 0.0001), increased IL-1β concentrations in the duodenum and jejunum (p < 0.05), and increased concentrations of NF-κB p65 in the duodenum (p < 0.01), jejunum and ileum (p < 0.05). We observed high IL-1β reactivity in the muscle layer, myenteric neurons, and glial cells of the experimental group. GK rats also exhibited a significant reduction in submucosal neuron density in the jejunum and ileum, ganglionic hypertrophy in all intestinal segments studied (p < 0.0001), and a slower intestinal transit (about 25%) compared to controls.
CONCLUSIONS
The development of IR and T2DM in GK rats is associated with small intestine remodeling that includes marked alterations in small intestine morphology, local inflammation, and reduced intestinal transit.
Topics: Animals; Blood Glucose; Cytokines; Diabetes Mellitus, Type 2; Disease Models, Animal; Duodenum; Gastrointestinal Transit; Ileum; Inflammation Mediators; Insulin Resistance; Intestine, Small; Jejunum; Male; Myenteric Plexus; Rats, Wistar; Submucous Plexus; Rats
PubMed: 33580916
DOI: 10.14814/phy2.14755 -
The New England Journal of Medicine Oct 2020Eosinophilic gastritis and duodenitis are characterized by gastrointestinal mucosal eosinophilia, chronic symptoms, impaired quality of life, and a lack of adequate... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Eosinophilic gastritis and duodenitis are characterized by gastrointestinal mucosal eosinophilia, chronic symptoms, impaired quality of life, and a lack of adequate treatments. Mast-cell activity may contribute to the pathogenesis of the conditions. AK002 (lirentelimab) is an anti-Siglec-8 antibody that depletes eosinophils and inhibits mast cells and that has shown potential in animal models as a treatment for eosinophilic gastritis and duodenitis.
METHODS
In this phase 2 trial, we randomly assigned adults who had symptomatic eosinophilic gastritis, eosinophilic duodenitis, or both conditions in a 1:1:1 ratio to receive four monthly infusions of low-dose AK002, high-dose AK002, or placebo. The primary end point was the change in gastrointestinal eosinophil count from baseline to 2 weeks after the final dose; to maximize statistical power, we evaluated this end point in the placebo group as compared with the combined AK002 group. Secondary end points were treatment response (>30% reduction in total symptom score and >75% reduction in gastrointestinal eosinophil count) and the change in total symptom score.
RESULTS
Of the 65 patients who underwent randomization, 43 were assigned to receive AK002 and 22 were assigned to receive placebo. The mean percentage change in gastrointestinal eosinophil count was -86% in the combined AK002 group, as compared with 9% in the placebo group (least-squares mean difference, -98 percentage points; 95% confidence interval [CI], -121 to -76; P<0.001). Treatment response occurred in 63% of the patients who received AK002 and in 5% of the patients who received placebo (difference, 58 percentage points; 95% CI, 36 to 74; P<0.001). The mean change in total symptom score was -48% with AK002 and -22% with placebo (least-squares mean difference, -26 percentage points; 95% CI, -44 to -9; P = 0.004). Adverse events associated with AK002 were similar to those with placebo, with the exception of higher percentages of patients having mild-to-moderate infusion-related reactions with AK002 (60% in the combined AK002 group and 23% in the placebo group).
CONCLUSIONS
In patients with eosinophilic gastritis or duodenitis, AK002 reduced gastrointestinal eosinophils and symptoms. Infusion-related reactions were more common with AK002 than with placebo. (Funded by Allakos; ENIGMA ClinicalTrials.gov number, NCT03496571.).
Topics: Adolescent; Adult; Aged; Antibodies, Monoclonal, Humanized; Antigens, CD; Antigens, Differentiation, B-Lymphocyte; Dose-Response Relationship, Drug; Double-Blind Method; Duodenitis; Enteritis; Eosinophilia; Eosinophils; Female; Gastritis; Gastrointestinal Tract; Humans; Infusions, Intravenous; Lectins; Leukocyte Count; Male; Middle Aged; Young Adult
PubMed: 33085861
DOI: 10.1056/NEJMoa2012047 -
Polish Journal of Radiology 2020Herein we reviewed the computed tomography (CT) findings of a spectrum of pathological entities affecting the duodenum. We discuss the CT findings of some congenital,... (Review)
Review
Herein we reviewed the computed tomography (CT) findings of a spectrum of pathological entities affecting the duodenum. We discuss the CT findings of some congenital, inflammatory, traumatic, and neoplastic pathologies of the duodenum along with the conventional barium studies of selected conditions. Pathologies of this C-shaped intestinal segment, derived from both foregut and midgut, are often overlooked in clinical practice and radiological literature. While congenital anomalies like duplication cysts and diverticula are usually asymptomatic, annular pancreas and malrotation may manifest in the first decade of life. Primary as well as secondary involvement of the duodenum by various disease processes can be evaluated by careful CT technique and proper attention to the duodenum. Among congenital conditions, annular pancreas, duplication cyst, superior mesenteric artery syndrome, midgut volvulus, and diverticula are presented. Duodenal involvement in adenocarcinoma, lymphoma, gastrointestinal stromal tumours, Crohn's disease, and groove pancreatitis are discussed. Duodenal wall haematoma and traumatic duodenal perforation causing pneumoretroperitoneum in two patients after blunt trauma of the abdomen are also illustrated. CT provides superb anatomic detail and offers high diagnostic specificity for the detection of duodenal pathologies because it allows direct imaging of the intestinal wall, secondary signs of bowel disease within the surrounding mesentery, and abnormal findings in adjacent structures. Primary duodenal malignancies and local extension from adjacent malignancies can be diagnosed by CT reliably. CT also plays a vital role in the diagnosis of traumatic duodenal injury by differentiating between mural haematoma and a duodenal perforation because the latter requires immediate surgical intervention.
PubMed: 32612721
DOI: 10.5114/pjr.2020.95477 -
Gastroenterology Mar 2022Excessive shedding of apoptotic enterocytes into the intestinal lumen is observed in inflammatory bowel disease and is correlated with disease relapse. Based on their...
BACKGROUND & AIMS
Excessive shedding of apoptotic enterocytes into the intestinal lumen is observed in inflammatory bowel disease and is correlated with disease relapse. Based on their cytolytic capacity and surveillance behavior, we investigated whether intraepithelial lymphocytes expressing the γδ T cell receptor (γδ IELs) are actively involved in the shedding of enterocytes into the lumen.
METHODS
Intravital microscopy was performed on GFP γδ T cell reporter mice treated with intraperitoneal lipopolysaccharide (10 mg/kg) for 90 minutes to induce tumor necrosis factor-mediated apoptosis. Cell shedding in various knockout or transgenic mice in the presence or absence of blocking antibody was quantified by immunostaining for ZO-1 funnels and cleaved caspase-3 (CC3). Granzyme A and granzyme B release from ex vivo-stimulated γδ IELs was quantified by enzyme-linked immunosorbent assay. Immunostaining for γδ T cell receptor and CC3 was performed on duodenal and ileal biopsies from controls and patients with Crohn's disease.
RESULTS
Intravital microscopy of lipopolysaccharide-treated mice revealed that γδ IELs make extended contact with shedding enterocytes. These prolonged interactions require CD103 engagement by E-cadherin, and CD103 knockout or blockade significantly reduced lipopolysaccharide-induced shedding. Furthermore, we found that granzymes A and B, but not perforin, are required for cell shedding. These extracellular granzymes are released by γδ IELs both constitutively and after CD103/E-cadherin ligation. Moreover, we found that the frequency of γδ IEL localization to CC3-positive enterocytes is increased in Crohn's disease biopsies compared with healthy controls.
CONCLUSIONS
Our results uncover a previously unrecognized role for γδ IELs in facilitating tumor necrosis factor-mediated shedding of apoptotic enterocytes via CD103-mediated extracellular granzyme release.
Topics: Adolescent; Adult; Animals; Antigens, CD; Apoptosis; Cadherins; Caspase 3; Crohn Disease; Duodenum; Enterocytes; Female; Gene Knockdown Techniques; Granzymes; Humans; Ileum; Integrin alpha Chains; Intestinal Mucosa; Intraepithelial Lymphocytes; Intravital Microscopy; Jejunum; Lipopolysaccharides; Male; Mice; Mice, Knockout; Middle Aged; Receptors, Antigen, T-Cell, gamma-delta; Tumor Necrosis Factor-alpha; Young Adult
PubMed: 34861219
DOI: 10.1053/j.gastro.2021.11.028 -
Revista Espanola de Enfermedades... Apr 202459-year-old man, smoker, diabetic and hypertensive. He went to the ER due to fixed abdominal pain in the epigastrium, diaphoresis, dizziness, nausea, and "coffee...
59-year-old man, smoker, diabetic and hypertensive. He went to the ER due to fixed abdominal pain in the epigastrium, diaphoresis, dizziness, nausea, and "coffee grounds" vomiting. On examination he presented abdominal distension and pain on palpation in the epigastrium, without peritonism. He had a BP of 235/100 mmHg and in the blood-tests, leukocytosis with neutrophilia and normal hemoglobin. An urgent abdominal CT scan was performed, identifying a 5x6 cm nodular lesion of homogeneous density attached to the wall of the second and third duodenal portions that compressed the lumen, with two vessels with active bleeding within it. Therefore, percutaneous embolization of the gastroduodenal artery was performed. Subsequently, the patient suffered an episode of severe acute pancreatitis that required ICU admission. Finally, he presented a good clinical evolution with ceasing of pain, complete reabsorption of the hematoma and resolution of the obstructive symptoms.
Topics: Male; Humans; Acute Disease; Pancreatitis; Hematoma; Duodenal Diseases; Gastrointestinal Hemorrhage; Abdominal Pain; Hematemesis
PubMed: 37706445
DOI: 10.17235/reed.2023.9793/2023 -
Blood Jun 2023Iron is an essential cellular metal that is important for many physiological functions including erythropoiesis and host defense. It is absorbed from the diet in the...
Iron is an essential cellular metal that is important for many physiological functions including erythropoiesis and host defense. It is absorbed from the diet in the duodenum and loaded onto transferrin (Tf), the main iron transport protein. Inefficient dietary iron uptake promotes many diseases, but mechanisms regulating iron absorption remain poorly understood. By assessing mice that harbor a macrophage-specific deletion of the tuberous sclerosis complex 2 (Tsc2), a negative regulator of mechanistic target of rapamycin complex 1 (mTORC1), we found that these mice possessed various defects in iron metabolism, including defective steady-state erythropoiesis and a reduced saturation of Tf with iron. This iron deficiency phenotype was associated with an iron import block from the duodenal epithelial cells into the circulation. Activation of mTORC1 in villous duodenal CD68+ macrophages induced serine protease expression and promoted local degradation of Tf, whereas the depletion of macrophages in mice increased Tf levels. Inhibition of mTORC1 with everolimus or serine protease activity with nafamostat restored Tf levels and Tf saturation in the Tsc2-deficient mice. Physiologically, Tf levels were regulated in the duodenum during the prandial process and Citrobacter rodentium infection. These data suggest that duodenal macrophages determine iron transfer to the circulation by controlling Tf availability in the lamina propria villi.
Topics: Mice; Animals; Transferrin; Iron, Dietary; Iron; Mechanistic Target of Rapamycin Complex 1; Diet; Duodenum; Receptors, Transferrin
PubMed: 37018657
DOI: 10.1182/blood.2022016632 -
Digestive Diseases and Sciences Jun 2023Food-specific immunoglobulin G4 (FS-IgG4) is associated with eosinophilic esophagitis (EoE); however, it is not clear whether production is limited to the esophagus.
BACKGROUND
Food-specific immunoglobulin G4 (FS-IgG4) is associated with eosinophilic esophagitis (EoE); however, it is not clear whether production is limited to the esophagus.
AIMS
To assess FS-IgG4 levels in the upper gastrointestinal tract and plasma and compare these with endoscopic disease severity, tissue eosinophil counts, and patient-reported symptoms.
METHODS
We examined prospectively banked plasma, throat swabs, and upper gastrointestinal biopsies (esophagus, gastric antrum, and duodenum) from control (n = 15), active EoE (n = 24), and inactive EoE (n = 8) subjects undergoing upper endoscopy. Patient-reported symptoms were assessed using the EoE symptom activity index (EEsAI). Endoscopic findings were evaluated using the EoE endoscopic reference score (EREFS). Peak eosinophils per high-power field (eos/hpf) were assessed from esophageal biopsies. Biopsy homogenates and throat swabs were normalized for protein content and assessed for FS-IgG4 to milk, wheat, and egg.
RESULTS
Median FS-IgG4 for milk and wheat was significantly increased in the plasma, throat swabs, esophagus, stomach, and duodenum of active EoE subjects compared to controls. No significant differences for milk- or wheat-IgG4 were observed between active and inactive EoE subjects. Among the gastrointestinal sites sampled, FS-IgG4 levels were highest in the esophagus. Esophageal FS-IgG4 for all foods correlated significantly across all sites sampled (r ≥ 0.59, p < 0.05). Among subjects with EoE, esophageal FS-IgG4 correlated significantly with peak eos/hpf (milk and wheat) and total EREFS (milk). EEsAI scores and esophageal FS-IgG4 levels did not correlate.
CONCLUSIONS
Milk and wheat FS-IgG4 levels are elevated in plasma and throughout the upper gastrointestinal tract in EoE subjects and correlate with endoscopic findings and esophageal eosinophilia.
Topics: Humans; Immunoglobulin G; Food Hypersensitivity; Eosinophilic Esophagitis; Prospective Studies; Case-Control Studies; Eosinophils; Endoscopy, Gastrointestinal; Biomarkers; Upper Gastrointestinal Tract; Male; Female; Adult; Middle Aged; Aged
PubMed: 36973521
DOI: 10.1007/s10620-023-07924-2 -
Gastroenterology Nursing : the Official...The incidence of COVID-19 gastrointestinal manifestations has been reported to range from 3% to 61%. There are limited data on the incidence rates and risk factors... (Review)
Review
The incidence of COVID-19 gastrointestinal manifestations has been reported to range from 3% to 61%. There are limited data on the incidence rates and risk factors associated with gastrointestinal bleeding (GIB) in patients with COVID-19. A rapid review has been designed to investigate whether there is a relationship between COVID-19 and GIB in adult patients. PubMed, CINAHL, EMBASE, Cochrane Library, and Scopus databases have been analyzed. A total of 129 studies were found; 29 full texts were analyzed, and of these, 20 were found to be relevant to the topic. The key findings of the included studies present an overall GIB rate in COVID-19 patients ranging from 1.1% to 13%. The bleeding involves mucosal damage of the duodenum, stomach, colon, and rectum. The management of gastrointestinal bleeding could be conservative. The use of fecal diversion systems for the management of diarrhea in COVID-19 patients should be minimized and closely evaluated for the risk of rectal mucosal damages and erosions. It is recommended to provide an accurate nutritional assessment; an early setting up of enteral nutrition, if not contraindicated, can help protect the gut mucosa of patients and restore normal intestinal flora. Larger cohort studies are needed to increase the information about this topic.
Topics: Adult; COVID-19; Colon; Enteral Nutrition; Gastrointestinal Hemorrhage; Humans; Rectum
PubMed: 35833732
DOI: 10.1097/SGA.0000000000000676 -
Colombia Medica (Cali, Colombia) May 2021The overall incidence of duodenal injuries in severely injured trauma patients is between 0.2 to 0.6% and the overall prevalence in those suffering from abdominal trauma... (Review)
Review
The overall incidence of duodenal injuries in severely injured trauma patients is between 0.2 to 0.6% and the overall prevalence in those suffering from abdominal trauma is 3 to 5%. Approximately 80% of these cases are secondary to penetrating trauma, commonly associated with vascular and adjacent organ injuries. Therefore, defining the best surgical treatment algorithm remains controversial. Mild to moderate duodenal trauma is currently managed via primary repair and simple surgical techniques. However, severe injuries have required complex surgical techniques without significant favorable outcomes and a consequential increase in mortality rates. This article aims to delineate the experience in the surgical management of penetrating duodenal injuries via the creation of a practical and effective algorithm that includes basic principles of damage control surgery that sticks to the philosophy of "Less is Better". Surgical management of all penetrating duodenal trauma should always default when possible to primary repair. When confronted with a complex duodenal injury, hemodynamic instability, and/or significant associated injuries, the default should be damage control surgery. Definitive reconstructive surgery should be postponed until the patient has been adequately resuscitated and the diamond of death has been corrected.
Topics: Algorithms; Duodenum; Hemorrhage; Humans; Medical Illustration; Wounds, Penetrating
PubMed: 34188326
DOI: 10.25100/cm.v52i2.4509