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GeroScience Apr 2024The detailed comorbidity patterns of community-dwelling older adults have not yet been explored. This study employed a network-based approach to investigate the...
The detailed comorbidity patterns of community-dwelling older adults have not yet been explored. This study employed a network-based approach to investigate the comorbidity patterns of community-dwelling older adults living alone. The sample comprised a cross-sectional cohort of adults 65 or older living alone in a Korean city (n = 1041; mean age = 77.7 years, 77.6% women). A comorbidity network analysis that estimates networks aggregated from measures of significant co-occurrence between pairs of diseases was employed to investigate comorbid associations between 31 chronic conditions. A cluster detection algorithm was employed to identify specific clusters of comorbidities. The association strength was expressed as the observed-to-expected ratio (OER). As a result, fifteen diseases were interconnected within the network (OER > 1, p-value < .05). While hypertension had a high prevalence, osteoporosis was the most central disease, co-occurring with numerous other diseases. The strongest associations among comorbidities were found between thyroid disease and urinary incontinence, chronic otitis media and osteoporosis, gastric duodenal ulcer/gastritis and anemia, and depression and gastric duodenal ulcer/gastritis (OER > 1.85). Three distinct clusters were identified as follows: (a) cataracts, osteoporosis, chronic otitis media, osteoarthritis/rheumatism, low back pain/sciatica, urinary incontinence, post-accident sequelae, and thyroid diseases; (b) hyperlipidemia, diabetes mellitus, and hypertension; and (c) depression, skin disease, gastric duodenal ulcer/gastritis, and anemia. The results may prove valuable in guiding the early diagnosis, management, and treatment of comorbidities in older adults living alone.
Topics: Humans; Female; Aged; Male; Independent Living; Cross-Sectional Studies; Duodenal Ulcer; Home Environment; Comorbidity; Hypertension; Osteoporosis; Gastritis; Anemia; Otitis Media; Urinary Incontinence
PubMed: 37924440
DOI: 10.1007/s11357-023-00987-z -
Molecular Cancer Research : MCR Jun 2024The pathogenesis of duodenal tumors in the inherited tumor syndromes familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP) is poorly understood. This...
UNLABELLED
The pathogenesis of duodenal tumors in the inherited tumor syndromes familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP) is poorly understood. This study aimed to identify genes that are significantly mutated in these tumors and to explore the effects of these mutations. Whole exome and whole transcriptome sequencing identified recurrent somatic coding variants of phosphatidylinositol N-acetylglucosaminyltransferase subunit A (PIGA) in 19/70 (27%) FAP and MAP duodenal adenomas, and further confirmed the established driver roles for APC and KRAS. PIGA catalyzes the first step in glycosylphosphatidylinositol (GPI) anchor biosynthesis. Flow cytometry of PIGA-mutant adenoma-derived and CRISPR-edited duodenal organoids confirmed loss of GPI anchors in duodenal epithelial cells and transcriptional profiling of duodenal adenomas revealed transcriptional signatures associated with loss of PIGA.
IMPLICATIONS
PIGA somatic mutation in duodenal tumors from patients with FAP and MAP and loss of membrane GPI-anchors may present new opportunities for understanding and intervention in duodenal tumorigenesis.
Topics: Humans; Glycosylphosphatidylinositols; Duodenal Neoplasms; Mutation; Adenomatous Polyposis Coli; Membrane Proteins; Carcinogenesis; Male; Female
PubMed: 38546397
DOI: 10.1158/1541-7786.MCR-23-0810 -
Frontiers in Immunology 2024Duodenogastric reflux (DGR) has been linked to the onset of gastric cancer (GC), although the precise mechanism is yet obscure. Herein, we aimed to investigate how...
Duodenogastric reflux (DGR) has been linked to the onset of gastric cancer (GC), although the precise mechanism is yet obscure. Herein, we aimed to investigate how refluxed bile acids (BAs) and macrophages are involved in gastric carcinogenesis. In both active human bile reflux gastritis and the murine DGR model, ubiquitin specific protease 50 (USP50) was dramatically raised, and macrophages were the principal leukocyte subset that upregulated USP50 expression. Enhancing USP50 expression amplified bile acid-induced NLR family pyrin domain containing 3 (NLRP3) inflammasome activation and subsequent high-mobility group box protein 1 (HMGB1) release, while USP50 deficiency resulted in the reversed alteration. Mechanistically, USP50 interacted with and deubiquitinated apoptosis-associated speck-like protein containing CARD (ASC) to activate NLRP3 inflammasome. The release of HMGB1 contributes to gastric tumorigenesis by PI3K/AKT and MAPK/ERK pathways. These results may provide new insights into bile reflux-related gastric carcinogenesis and options for the prevention of DGR-associated GC.
Topics: Animals; Humans; Mice; Bile Reflux; Carcinogenesis; Cell Transformation, Neoplastic; Duodenogastric Reflux; HMGB1 Protein; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Phosphatidylinositol 3-Kinases
PubMed: 38469295
DOI: 10.3389/fimmu.2024.1326137 -
Endoscopy International Open Jun 2024There is limited consensus on the optimal method for measuring disease severity in familial adenomatous polyposis (FAP). We aimed to systematically review the operating... (Review)
Review
There is limited consensus on the optimal method for measuring disease severity in familial adenomatous polyposis (FAP). We aimed to systematically review the operating properties of existing endoscopic severity indices for FAP. We searched MEDLINE, EMBASE, and the Cochrane Library from inception to February 2023 to identify randomized controlled trials (RCTs) that utilized endoscopic outcomes or studies that evaluated the operating properties of endoscopic disease severity indices in FAP. A total of 134 studies were included. We evaluated scoring indices and component items of scoring indices, such as polyp count, polyp size, and histology. Partial validation was observed for polyp count and size. The most commonly reported scoring index was the Spigelman classification system, which was used for assessing the severity of duodenal involvement. A single study reported almost perfect interobserver and intra-observer agreement for this system. The InSIGHT polyposis staging system, which was used for assessing colorectal polyp burden, has been partially validated. It showed substantial interobserver reliability; however, the intra-observer reliability was not assessed. Novel criteria for high-risk gastric polyps have been developed and assessed for interobserver reliability. However, these criteria showed a poor level of agreement. Other scoring indices assessing the anal transition zone, duodenal, and colorectal polyps have not undergone validation. There are no fully validated endoscopic disease severity indices for FAP. Development and validation of a reliable and responsive endoscopic disease severity instrument will be informative for clinical care and RCTs of pharmacological therapies for FAP.
PubMed: 38904059
DOI: 10.1055/a-2330-8037 -
Clinical Gastroenterology and... Jun 2024Villus height to crypt depth ratio (Vh:Cd) and intraepithelial lymphocytes (IEL) are key measures of histology of the small intestine in celiac disease. Although the...
BACKGROUND & AIMS
Villus height to crypt depth ratio (Vh:Cd) and intraepithelial lymphocytes (IEL) are key measures of histology of the small intestine in celiac disease. Although the field of celiac disease has advanced, there remains no broadly accepted measure of mucosal injury. We assessed whether a composite Vh:Cd and IEL scale (VCIEL) can improve accuracy and statistical precision for assessing histology, compared with individual measures.
METHODS
The formulation of the VCIEL composite histologic scale was based on combining the Vh:Cd and IEL measurements for individual patients with equal weighting, by converting each scale to a fraction of their standard deviation and summing the results. The VCIEL formula was applied to several clinical trials and the results for Vh:Cd and IEL were compared with those for VCIEL with regards to clinical significance (effect size) and statistical significance.
RESULTS
For the ALV003-1021 trial, we observed an effect size and P value (analysis of covariance) of 1.37 and 0.038 for ΔVh:Cd, 1.17 and 0.005 for ΔIEL, and 1.86 and 0.004 for ΔVCIEL. For the similar gluten-challenge IMGX003-NCCIH-1721 trial, the corresponding results were 0.76 and 0.057 for ΔVh:Cd, 0.98 and 0.018 for ΔIEL, and 1.14 and 0.007 for ΔVCIEL. Similar improvements with the use of VCIEL over individual Vh:Cd and IEL measures were observed for other studies, including a nontherapeutic gluten challenge study.
CONCLUSIONS
The composite VCIEL scale combining Vh:Cd and IEL values seems to improve accuracy and statistical precision compared with either component alone.
Topics: Celiac Disease; Humans; Intestinal Mucosa; Duodenum; Biopsy; Histocytochemistry
PubMed: 37952751
DOI: 10.1016/j.cgh.2023.10.031 -
Frontiers in Microbiology 2023Recent an observational study has suggested a potential connection between gut microbiota (GM) and peptic ulcer diseases (PUDs), particularly gastric ulcer (GU) and...
BACKGROUND
Recent an observational study has suggested a potential connection between gut microbiota (GM) and peptic ulcer diseases (PUDs), particularly gastric ulcer (GU) and duodenal ulcer (DU). However, the causal connection remains unsure.
METHODS
A two-sample Mendelian randomization (MR) is carried out to explore the connection between the GM and DU or GU. Data on the GM comes from the MiBioGend database, and GU or DU data are based on the FinnGen database. One group of single nucleotide polymorphisms (SNPs) ( < 5 × 10) are served as instrumental variables (IVs). To obtain a more comprehensive conclusion, the other SNPs ( < 1 × 10) are selected as IVs. Inverse variance weighting (IVW) is used to determine the causal relationship.
RESULTS
At the level of < 1 × 10, the IVW analysis suggests that Clostridiaceae1, Butyriccoccus, and Peptcoccus have harmful effects on GU, while LachnospiraceaeUCG004 and MollicutesRF9 have beneficial effects on GU. Then, in the case of DU, the IVW analysis suggested that Lentisphaeria, Negativicutes, Clostridiaceae1, ClostridiumseMnsustricto1, ErysipelotrichaceaeUCG003, LachnospiraceaeNC2004group, Selenomonadale, Victivallales, and Lentisphaerae have harmful effects, while Catenibacterium, Escherichia.Shigella, LachnospiraceaeUCG008, and Sutterella have beneficial effects. When < 5 × 10, IVW analysis suggests that GM has no significant influence on GU or DU.
CONCLUSION
This two-sample MR indicates a causal relationship between GM and GU or DU.
PubMed: 38274744
DOI: 10.3389/fmicb.2023.1277300 -
Allergy, Asthma, and Clinical... Dec 2023Non-esophageal eosinophilic gastrointestinal disorder (non-EoE-EGID) is a rare disease in which eosinophils infiltrate parts of the gastrointestinal tract other than the...
BACKGROUND
Non-esophageal eosinophilic gastrointestinal disorder (non-EoE-EGID) is a rare disease in which eosinophils infiltrate parts of the gastrointestinal tract other than the esophagus; however, the number of patients with non-EoE-EGID has been increasing in recent years. Owing to its chronic course with repeated relapses, it can lead to developmental delays due to malnutrition, especially in pediatric patients. No established treatment exists for non-EoE-EGID, necessitating long-term systemic corticosteroid administration. Although the efficacy of dupilumab, an anti-IL-4/13 receptor monoclonal antibody, for eosinophilic esophagitis, has been reported, only few reports have demonstrated its efficacy in non-EoE EGIDs.
CASE PRESENTATION
A 13-year-old boy developed non-EoE-EGID with duodenal ulcers, with chicken eggs as the trigger. He was successfully treated with an egg-free diet, proton pump inhibitors, and leukotriene receptor antagonists. However, at age 15, he developed worsening upper abdominal pain and difficulty eating. Blood analysis revealed eosinophilia; elevated erythrocyte sedimentation rate; and elevated levels of C-reactive protein, total immunoglobulin E, and thymic and activation-regulated chemokines. Upper gastrointestinal endoscopy revealed a duodenal ulcer with marked mucosal eosinophilic infiltration. Gastrointestinal symptoms persisted even after starting systemic steroids, making it difficult to reduce the steroid dose. Subcutaneous injection of dupilumab was initiated because of comorbid atopic dermatitis exacerbation. After 3 months, the gastrointestinal symptoms disappeared, and after 5 months, the duodenal ulcer disappeared and the eosinophil count decreased in the mucosa. Six months later, systemic steroids were discontinued, and the duodenal ulcer remained recurrence-free. The egg challenge test result was negative; therefore, the egg-free diet was discontinued. Blood eosinophil count and serum IL-5, IL-13, and eotaxin-3 levels decreased after dupilumab treatment. The serum levels of IL-5 and eotaxin-3 remained within normal ranges, although the blood eosinophil counts increased again after discontinuation of oral prednisolone.
CONCLUSIONS
Suppression of IL-4R/IL-13R-mediated signaling by dupilumab may improve abdominal symptoms and endoscopic and histologic findings in patients with non-EoE-EGID, leading to the discontinuation of systemic steroid administration and tolerance of causative foods.
PubMed: 38053199
DOI: 10.1186/s13223-023-00859-3 -
Clinics in Orthopedic Surgery Aug 2023Nonsteroidal anti-inflammatory drugs (NSAID) are currently among the most prescribed medications worldwide to relieve pain and reduce inflammation, especially in...
Development of Prediction Model Using Machine-Learning Algorithms for Nonsteroidal Anti-inflammatory Drug-Induced Gastric Ulcer in Osteoarthritis Patients: Retrospective Cohort Study of a Nationwide South Korean Cohort.
BACKGROUND
Nonsteroidal anti-inflammatory drugs (NSAID) are currently among the most prescribed medications worldwide to relieve pain and reduce inflammation, especially in patients suffering osteoarthritis (OA). However, NSAIDs are known to have adverse effects on the gastrointestinal system. If a gastric ulcer occurs, planned OA treatment needs to be changed, incurring additional treatment costs and causing discomfort for both patients and clinicians. Therefore, it is necessary to create a gastric ulcer prediction model that can reflect the detailed health status of each individual and to use it when making treatment plans.
METHODS
Using sample cohort data from 2008 to 2013 from the National Health Insurance Service in South Korea, we developed a prediction model for NSAID-induced gastric ulcers using machine-learning algorithms and investigated new risk factors associated with medication and comorbidities.
RESULTS
The population of the study consisted of 30,808 patients with OA who were treated with NSAIDs between 2008 and 2013. After a 2-year follow-up, these patients were divided into two groups: without gastric ulcer (n=29,579) and with gastric ulcer (n=1,229). Five machine-learning algorithms were used to develop the prediction model, and a gradient boosting machine (GBM) was selected as the model with the best performance (area under the curve, 0.896; 95% confidence interval, 0.883-0.909). The GBM identified 5 medications (loxoprofen, aceclofenac, talniflumate, meloxicam, and dexibuprofen) and 2 comorbidities (acute upper respiratory tract infection [AURI] and gastroesophageal reflux disease) as important features. AURI did not have a dose-response relationship, so it could not be interpreted as a significant risk factor even though it was initially detected as an important feature and improved the prediction performance.
CONCLUSIONS
We obtained a prediction model for NSAID-induced gastric ulcers using the GBM method. Since personal prescription period and the severity of comorbidities were considered numerically, individual patients' risk could be well reflected. The prediction model showed high performance and interpretability, so it is meaningful to both clinicians and NSAID users.
Topics: Humans; Stomach Ulcer; Retrospective Studies; Anti-Inflammatory Agents, Non-Steroidal; Osteoarthritis; Risk Factors
PubMed: 37529187
DOI: 10.4055/cios22240 -
Chirurgia (Bucharest, Romania : 1990) Dec 2023Helicobacter pylori, a gram-negative bacterium, has been identified as a major contributor to gastrointestinal diseases, ranging from gastritis and peptic ulcers to more... (Review)
Review
Helicobacter pylori, a gram-negative bacterium, has been identified as a major contributor to gastrointestinal diseases, ranging from gastritis and peptic ulcers to more severe complications such as gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. While pharmacological eradication therapies have been successful in managing H. pylori-associated diseases, the implications of this bacterium on surgical interventions remain a topic of ongoing research and clinical consideration. This comprehensive review aims to elucidate the intricate surgical implications of H. pylori infection. Recent data on the well-known relationship between and the development of gastroduodenal diseases, including peptic ulcers and gastric cancer, is analyzed. Concurrently, Helicobacter pylori infection may have a role in promoting colonic carcinogenesis and, more interestingly, it has also been linked to biliary tract cancers. The review highlights the evolving landscape of H. pylori management in the context of surgical interventions, accentuating the need for further research to delineate optimal strategies for preoperative screening, eradication therapies, and their impact on surgical outcomes and long-term patient prognosis. Comprehending the surgical ramifications of H. pylori infection remains crucial, emphasizing the significance of interdisciplinary approaches and ongoing research effort aimed at enhancing patient care.
Topics: Humans; Helicobacter Infections; Helicobacter pylori; Treatment Outcome; Peptic Ulcer; Gastritis; Stomach Neoplasms; Lymphoma, B-Cell, Marginal Zone
PubMed: 38228590
DOI: 10.21614/chirurgia.2023.v.118.i.6.p.568 -
Frontiers in Medicine 2023Contradictory evidence suggested gastric xanthelasma (GX) was associated with some upper gastrointestinal (GI) diseases. Additionally, no research has been performed on...
BACKGROUND
Contradictory evidence suggested gastric xanthelasma (GX) was associated with some upper gastrointestinal (GI) diseases. Additionally, no research has been performed on the relationship between esophageal/duodenal xanthelasma and upper GI diseases.
METHODS
Individuals who underwent esophagogastroduodenoscopy at Tongji Hospital, Tongji Medical College, participated in this retrospective study. This study evaluated whether the risk of GX or esophageal/duodenal xanthelasma was influenced by the following gastroesophageal diseases: superficial gastritis, gastric polyp, bile reflux, peptic ulcer, reflux esophagitis, Barrett's esophagus, esophageal cancer, atrophic gastritis (AG), intestinal metaplasia (IM), dysplasia, gastric cancer, and () infection. Furthermore, subgroup analysis was conducted to establish the relationship between the number of GX and upper GI diseases.
RESULTS
Of the 69,071 subjects reviewed, 1,220 (1.77%) had GX, and 54 (0.08%) had esophageal/duodenal xanthelasma. There was no difference in the prevalence of upper GI diseases between patients with and without esophageal/duodenal xanthelasma. Nevertheless, compared with non-xanthelasma patients, GX patients had a greater proportion of AG, IM, dysplasia, gastric cancer, and infection and a lower incidence of superficial gastritis ( < 0.05). The multivariate logistic regression analysis indicated AG (OR = 1.83, 95%CI: 1.56-2.16), IM (OR = 2.42, 95%CI: 2.41-2.85), and infection (OR = 1.32, 95%CI: 1.17-1.50) were independent risk factors for GX. In addition, patients with multiple GXs had a higher rate of AG and IM than those with single GX.
CONCLUSION
Esophageal/duodenal xanthelasma may not be associated with upper GI diseases, and further research is needed to support this hypothesis. Notably, GX, especially multiple GXs, may be a more easily detected warning sign of AG, IM, or infection.
PubMed: 37727758
DOI: 10.3389/fmed.2023.1252346