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EBioMedicine May 2024The causal associations of physical activity and sedentary behavior with the risk of gastrointestinal disease are unclear. We performed a Mendelian randomization...
BACKGROUND
The causal associations of physical activity and sedentary behavior with the risk of gastrointestinal disease are unclear. We performed a Mendelian randomization analysis to examine these associations.
METHODS
Genetic instruments associated with leisure screen time (LST, an indicator of a sedentary lifestyle) and moderate-to-vigorous intensity physical activity (MVPA) at the genome-wide significance (P < 5 × 10) level were selected from a genome-wide association study. Summary statistics for gastrointestinal diseases were obtained from the UK Biobank study, the FinnGen study, and large consortia. Multivariable MR analyses were conducted for genetically determined LST with adjustment for MVPA and vice versa. We also performed multivariable MR with adjustment for genetically proxied smoking, body mass index (BMI), waist-to-hip ratio, type 2 diabetes, and fasting insulin for both exposures.
FINDINGS
Genetically proxied longer LST was associated with an increased risk of gastrointestinal reflux, gastric ulcer, duodenal ulcer, chronic gastritis, irritable bowel syndrome, diverticular disease, Crohn's disease, ulcerative colitis, non-alcoholic fatty liver disease, alcoholic liver disease, cholangitis, cholecystitis, cholelithiasis, acute pancreatitis, chronic pancreatitis, and acute appendicitis. Most associations remained after adjustment for genetic liability to MVPA. Genetic liability to MVPA was associated with decreased risk of gastroesophageal reflux, gastric ulcer, chronic gastritis, irritable bowel syndrome, cholecystitis, cholelithiasis, acute and chronic pancreatitis. The associations attenuated albeit directionally remained after adjusting for genetically predicted LST. Multivariable MR analysis found that BMI and type 2 diabetes mediated the associations of LST and MVPA with several gastrointestinal diseases.
INTERPRETATION
The study suggests that a sedentary lifestyle may play a causal role in the development of many gastrointestinal diseases.
FUNDING
Natural Science Fund for Distinguished Young Scholars of Zhejiang Province (LR22H260001), Natural Science Foundation of Hunan Province (2021JJ30999), Swedish Heart-Lung Foundation (Hjärt-Lungfonden, 20210351), Swedish Research Council (Vetenskapsrådet, 2019-00977), Swedish Cancer Society (Cancerfonden), the Wellcome Trust (225790/7/22/Z), United Kingdom Research and Innovation Medical Research Council (MC_UU_00002/7) and National Institute for Health Research Cambridge Biomedical Research Centre (NHIR203312).
Topics: Humans; Mendelian Randomization Analysis; Sedentary Behavior; Exercise; Gastrointestinal Diseases; Genome-Wide Association Study; Polymorphism, Single Nucleotide; Genetic Predisposition to Disease; Risk Factors
PubMed: 38583262
DOI: 10.1016/j.ebiom.2024.105110 -
Zhongguo Ying Yong Sheng Li Xue Za Zhi... Dec 2023A peptic ulcer is a lesion (sore) on the stomach lining, or duodenum. Peptic ulcers are probably a twentieth-century condition. The ulcer disease continues to be a... (Review)
Review
A peptic ulcer is a lesion (sore) on the stomach lining, or duodenum. Peptic ulcers are probably a twentieth-century condition. The ulcer disease continues to be a significant source of worldwide morbidity and mortality. The Gastrointestinal ulcers and duodenal ulcers are considered the two most extreme types of peptic ulcers. Peptic ulcers are found to be caused by an excess of violent factors including Hydrochloric acid (HCL) pepsin, refluxed bile leukotrienes (LT), reactive oxygen species (ROS) and protective factors, these include mucus-bicarbonate barrier functions, prostaglandins (PGs), mucosal blood flow, cell regeneration and migration, non-enzymatic and enzymatic and certain growth factors. The primary cause of peptic ulcer disease is pylori infection and the use of NSAIDs. This review article underscores the importance of a multidisciplinary approach in the management of ulcers to improve patient outcomes and quality of life.
Topics: Humans; Peptic Ulcer
PubMed: 38755116
DOI: 10.62958/j.cjap.2023.006 -
International Journal of Cancer Apr 2024Infection by certain pathogens is associated with cancer development. We conducted a case-cohort study of ~2500 incident cases of esophageal, gastric and duodenal...
Infection by certain pathogens is associated with cancer development. We conducted a case-cohort study of ~2500 incident cases of esophageal, gastric and duodenal cancer, and gastric and duodenal ulcer and a randomly selected subcohort of ~2000 individuals within the China Kadoorie Biobank study of >0.5 million adults. We used a bead-based multiplex serology assay to measure antibodies against 19 pathogens (total 43 antigens) in baseline plasma samples. Associations between pathogens and antigen-specific antibodies with risks of site-specific cancers and ulcers were assessed using Cox regression fitted using the Prentice pseudo-partial likelihood. Seroprevalence varied for different pathogens, from 0.7% for Hepatitis C virus (HCV) to 99.8% for Epstein-Barr virus (EBV) in the subcohort. Compared to participants seronegative for the corresponding pathogen, Helicobacter pylori seropositivity was associated with a higher risk of non-cardia (adjusted hazard ratio [HR] 2.73 [95% CI: 2.09-3.58]) and cardia (1.67 [1.18-2.38]) gastric cancer and duodenal ulcer (2.71 [1.79-4.08]). HCV was associated with a higher risk of duodenal cancer (6.23 [1.52-25.62]) and Hepatitis B virus was associated with higher risk of duodenal ulcer (1.46 [1.04-2.05]). There were some associations of antibodies again some herpesviruses and human papillomaviruses with risks of gastrointestinal cancers and ulcers but these should be interpreted with caution. This first study of multiple pathogens with risk of gastrointestinal cancers and ulcers demonstrated that several pathogens are associated with risks of gastrointestinal cancers and ulcers. This will inform future investigations into the role of infection in the etiology of these diseases.
Topics: Adult; Humans; Cohort Studies; Duodenal Ulcer; Ulcer; Duodenal Neoplasms; Seroepidemiologic Studies; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Cardia; Gastrointestinal Neoplasms; Hepatitis C; Helicobacter Infections; Helicobacter pylori
PubMed: 38108203
DOI: 10.1002/ijc.34814 -
Pharmaceuticals (Basel, Switzerland) Dec 2023We reviewed gastric ulcer healing by dopamine considering several distinctive duodenal key points. Selye and Szabo describe the cysteamine-induced duodenal ulcer in rats... (Review)
Review
We reviewed gastric ulcer healing by dopamine considering several distinctive duodenal key points. Selye and Szabo describe the cysteamine-induced duodenal ulcer in rats as a duodenal stress ulcer in patients. Szabo's cysteamine duodenal ulcer as the dopamine duodenal healing and cysteamine as a dopamine antagonist signifies the dopamine agonists anti-ulcer effect and dopamine antagonists ulcerogenic effect. From these viewpoints, we focused on dopamine and gastric ulcer healing. We mentioned antecedent studies on the dopamine presence in the stomach and gastric juice. Then we reviewed, in the timeline, therapy significance arising from the anti-ulcer potency of the various dopamine agonists, which is highly prevailing over the quite persistent beneficial evidence arising from the various dopamine antagonists. Meanwhile, the beneficial effects of several peptides (i.e., amylin, cholecystokinin, leptin, and stable gastric pentadecapeptide BPC 157, suggested as an acting mediator of the dopamine brain-gut axis) were included in the dopamine gastric ulcer story. We attempt to resolve dopamine agonists/antagonists issue with the dopamine significance in the stress (cysteamine as a prototype of the duodenal stress ulcer), and cytoprotection (cysteamine in small dose as a prototype of the cytoprotective agents; cysteamine duodenal ulcer in gastrectomized rats). Thereby, along with dopamine agonists' beneficial effects, in special circumstances, dopamine antagonists having their own ulcerogenic effect may act as "mild stress (or)" or "small irritant" counteracting subsequent strong alcohol or stress procedure-induced severe lesions in this particular tissue. Finally, in the conclusion, as a new improvement in further therapy, we emphasized the advantages of the dopamine agents' application in lower gastrointestinal tract therapy.
PubMed: 38139825
DOI: 10.3390/ph16121699 -
World Journal of Clinical Cases May 2024In the context of mediastinal emphysema/pneumomediastinum, the main aetiologies are associated with oesophageal perforation, lung pathology or post head and neck surgery...
In the context of mediastinal emphysema/pneumomediastinum, the main aetiologies are associated with oesophageal perforation, lung pathology or post head and neck surgery related. The main way to differentiate the pathologies would be through Computed Tomographic Imaging of the Thorax and abdomen with oral and intravenous contrast in the context of triple phase imaging. The causes of pneumomediastinum should be differentiated between traumatic and non-traumatic. Oesophageal perforation (Boerhaave syndrome) is associated with Mackler's triad in upto 50% of patients (severe retrosternal chest pain, pneumomediastinum, mediastinitis). Whereas in cases of lung pathology this can be associated with pneumothorax and pleural effusion.
PubMed: 38817226
DOI: 10.12998/wjcc.v12.i15.2479 -
Endoscopic and Histopathological Characteristics of Gastrointestinal Lymphoma: A Multicentric Study.Diagnostics (Basel, Switzerland) Aug 2023: Extranodal non-Hodgkin lymphoma (NHL) is more prevalent in the gastrointestinal (GI) tract than in other sites. This study aimed to determine the endoscopic...
: Extranodal non-Hodgkin lymphoma (NHL) is more prevalent in the gastrointestinal (GI) tract than in other sites. This study aimed to determine the endoscopic characteristics of primary gastrointestinal non-Hodgkin lymphomas. : We investigated 140 patients from three tertiary referral hospitals with primary malignant lymphoma of the gastrointestinal tract. Characteristics of the lesions were evaluated and analyzed using image-enhanced endoscopy, endoscopic ultrasound, and histopathology. : The median age was 60.5 (range: 11-99), and 59 (42.1%) were female. The most frequent complaint was abdominal pain (74.3%), followed by bloody feces (10%) and diarrhea (2.9%). B symptoms were observed in 15 (10.7%) patients. GI obstruction was the most common complication (10.0%), followed by hemorrhage (7.9%) and perforation (1.5%). Regarding endoscopic findings, the identified sites were the following: the stomach (61.4%), colon (10%), small intestine (10%), ileocecum (8.6%), rectum (6.4%), and duodenum (3.6%). Diffuse large B-cell lymphoma (DLBCL) and mucosa-associated lymphoid tissue (MALT) lymphoma are most prevalent in the stomach. was identified in 46 cases (39.0%), with MALT lymphoma being the most infected subtype. Nearly all gastrointestinal non-Hodgkin lymphomas manifested as superficial type (25-59.6%) and ulcer type (15.6-50%) under endoscopy. We found that fungating type and protruding with ulcer type were more frequent types of aggressive lymphomas (diffuse large B-cell lymphoma, mantle cell lymphoma, and T-cell lymphoma) compared to the indolent types (MALT lymphoma, follicular lymphoma, duodenal-type follicular lymphoma, and small lymphocytic lymphoma) ( < 0.05). : This study showed that most subtypes of gastrointestinal non-Hodgkin lymphomas exhibited same endoscopic features (superficial type and ulcer type). Aggressive gastrointestinal non-Hodgkin lymphomas (diffuse large B-cell lymphoma, mantle cell lymphoma, and T-cell lymphoma) were highly suspected when fungating lesions and protruding with ulcer lesions were encountered under endoscopy. Endoscopists should be aware of the connection between enhanced endoscopic characteristics and histological varieties of gastrointestinal lymphoma to improve diagnosis.
PubMed: 37685305
DOI: 10.3390/diagnostics13172767 -
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 -
Nature Genetics Dec 2023Peptic ulcer disease (PUD) refers to acid-induced injury of the digestive tract, occurring mainly in the stomach (gastric ulcer (GU)) or duodenum (duodenal ulcer (DU)).... (Meta-Analysis)
Meta-Analysis
Peptic ulcer disease (PUD) refers to acid-induced injury of the digestive tract, occurring mainly in the stomach (gastric ulcer (GU)) or duodenum (duodenal ulcer (DU)). In the present study, we conducted a large-scale, cross-ancestry meta-analysis of PUD combining genome-wide association studies with Japanese and European studies (52,032 cases and 905,344 controls), and discovered 25 new loci highly concordant across ancestries. An examination of GU and DU genetic architecture demonstrated that GUs shared the same risk loci as DUs, although with smaller genetic effect sizes and higher polygenicity than DUs, indicating higher heterogeneity of GUs. Helicobacter pylori (HP)-stratified analysis found an HP-related host genetic locus. Integrative analyses using bulk and single-cell transcriptome profiles highlighted the genetic factors of PUD being enriched in the highly expressed genes in stomach tissues, especially in somatostatin-producing D cells. Our results provide genetic evidence that gastrointestinal cell differentiations and hormone regulations are critical in PUD etiology.
Topics: Humans; East Asian People; Genome-Wide Association Study; Peptic Ulcer; Stomach Ulcer; Duodenal Ulcer
PubMed: 38036781
DOI: 10.1038/s41588-023-01569-7 -
Clinical and Translational... Jul 2023Keverprazan is a novel potassium-competitive acid blocker for the treatment of acid-related disorders requiring potent acid inhibition. This study aimed to establish the... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Keverprazan is a novel potassium-competitive acid blocker for the treatment of acid-related disorders requiring potent acid inhibition. This study aimed to establish the noninferiority of keverprazan to lansoprazole in the treatment of patients with duodenal ulcer (DU).
METHODS
In this phase III, double-blind, multicenter study, 360 Chinese patients with endoscopically confirmed active DU were randomized 1:1 to take either keverprazan (20 mg) or lansoprazole (30 mg) treatment for up to 6 weeks. The primary end point was DU healing rate at week 6. The secondary end point was DU healing rate at week 4. Symptom improvement and safety were also assessed.
RESULTS
Based on the full analysis set, the cumulative healing rates at week 6 were 94.4% (170/180) and 93.3% (166/178) for keverprazan and lansoprazole, respectively (difference: 1.2%; 95% confidence intervel: -4.0%-6.5%). At week 4, the respective healing rates were 83.9% (151/180) and 80.3% (143/178). In the per protocol set, the 6-week healing rates in keverprazan and lansoprazole groups were 98.2% (163/166) and 97.6% (163/167), respectively (difference: 0.6%; 95% confidence intervel: -3.1%-4.4%); the 4-week healing rates were respectively 86.8% (144/166) and 85.6% (143/167). Keverprazan was noninferior to lansoprazole in DU healing after the treatment for 4 and 6 weeks. The incidence of treatment-emergent adverse events was comparable among groups.
DISCUSSION
Keverprazan 20 mg had a good safety profile and was noninferior to lansoprazole 30 mg once daily for DU healing.
Topics: Humans; Lansoprazole; Duodenal Ulcer; Anti-Ulcer Agents; Double-Blind Method
PubMed: 37235793
DOI: 10.14309/ctg.0000000000000602 -
Journal of Clinical Medicine Aug 2023The current design of biliopancreatic diversion with duodenal switch (BPD/DS) and single anastomosis duodenal-ileal bypass with sleeve (SADI-S) emphasizes the importance...
BACKGROUND
The current design of biliopancreatic diversion with duodenal switch (BPD/DS) and single anastomosis duodenal-ileal bypass with sleeve (SADI-S) emphasizes the importance of the pylorus' preservation to reduce the incidence of marginal ulcer (MU) and dumping. However, no institutional studies have yet reported data on their prevalence. We aimed to assess the incidence of MU and dumping after duodenal switch (DS) and identify the associative factors.
METHODS
A multi-center review of patients who underwent BPD/DS or SADI-S between 2008 and 2022. Baseline demographics, symptoms, and management of both complications were collected. Fisher's exact test was used for categorical variables and the independent -test for continuous variables.
RESULTS
A total of 919 patients were included (74.6% female; age 42.5 years; BMI 54.6 kg/m) with mean follow-up of 31.5 months. Eight patients (0.9%) developed MU and seven (0.8%) had dumping. Patients who developed MU were more likely to be using non-steroidal anti-inflammatory drugs (NSAID) ( = 0.006) and have a longer operation time ( = 0.047). Primary versus revisional surgery, and BDP/DS versus SADI-S were not associated with MU or dumping.
CONCLUSIONS
The incidences of MU and dumping after DS were low. NSAID use and a longer operation time were associated with an increased risk of MU, whereas dumping was attributed to poor dietary habits.
PubMed: 37685666
DOI: 10.3390/jcm12175600