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Cell Reports. Medicine Nov 2023Understanding the biological changes that precede a diagnosis of inflammatory bowel disease (IBD) could facilitate pre-emptive interventions, including risk factor...
Understanding the biological changes that precede a diagnosis of inflammatory bowel disease (IBD) could facilitate pre-emptive interventions, including risk factor modification, but this pre-clinical phase of disease remains poorly characterized. Using measurements from 17 hematological and biochemical parameters taken up to 10 years before diagnosis in over 20,000 IBD patients and population controls, we address this at massive scale. We observe widespread significant changes in multiple biochemical and hematological parameters that occur up to 8 years before diagnosis of Crohn's disease (CD) and up to 3 years before diagnosis of ulcerative colitis. These changes far exceed previous expectations regarding the length of this pre-diagnostic phase, revealing an opportunity for earlier intervention, especially in CD. In summary, using a nationwide, case-control dataset-obtained from the Danish registers-we provide a comprehensive characterization of the hematological and biochemical changes that occur in the pre-clinical phase of IBD.
Topics: Humans; Inflammatory Bowel Diseases; Colitis, Ulcerative; Crohn Disease; Risk Factors
PubMed: 37939713
DOI: 10.1016/j.xcrm.2023.101263 -
Frontiers in Immunology 2023Immune reconstitution inflammatory syndrome (IRIS) is characterized by exaggerated and dysregulated inflammatory responses that occur as a result of reconstitution of... (Review)
Review
Immune reconstitution inflammatory syndrome (IRIS) is characterized by exaggerated and dysregulated inflammatory responses that occur as a result of reconstitution of adaptive or innate immunity. A wide range of microorganisms have been found to be associated with IRIS, such as human immunodeficiency virus (HIV), and actinobacteria. Whipple disease (WD) is an infectious disorder caused by the Gram-positive bacterium and IRIS also serves as a complication during its treament. Although many of these pathological mechanisms are shared with related inflammatory disorders, IRIS in WD exhibits distinct features and is poorly described in the medical literature. Novel investigations of the intestinal mucosal immune system have provided new insights into the pathogenesis of IRIS, elucidating the interplay between systemic and local immune responses. These insights may be used to identify monitoring tools for disease prevention and to develop treatment strategies. Therefore, this review synthesizes these new concepts in WD IRIS to approach the feasibility of manipulating host immunity and immune reconstitution of inflammatory syndromes from a newer, more comprehensive perspective and study hypothetical options for the management of WD IRIS.
Topics: Humans; Whipple Disease; Immune Reconstitution Inflammatory Syndrome; Immune Reconstitution; Actinobacteria; Immunity, Innate
PubMed: 37901208
DOI: 10.3389/fimmu.2023.1265414 -
Biochimica Et Biophysica Acta.... Mar 2024Inflammatory bowel disease (IBD) encompasses a set of chronic inflammatory conditions, namely Crohn's disease and ulcerative colitis. Despite all advances in the... (Review)
Review
Inflammatory bowel disease (IBD) encompasses a set of chronic inflammatory conditions, namely Crohn's disease and ulcerative colitis. Despite all advances in the management of IBD, a definitive cure is not available, largely due to a lack of a holistic understanding of its etiology and pathophysiology. Several in vitro, in vivo, and ex vivo models have been developed over the past few decades in order to abbreviate remaining gaps. The establishment of reliable and predictable in vitro intestinal inflammation models may indeed provide valuable tools to expedite and validate the development of therapies for IBD. Three-dimensional (3D) models provide a more accurate representation of the different layers of the intestine, contributing to a stronger impact on drug screening and research on intestinal inflammation, and bridging the gap between in vitro and in vivo research. This work provides a critical overview on the state-of-the-art on existing 3D models of intestinal inflammation and discusses the remaining challenges, providing insights on possible pathways towards achieving IBD mimetic models. We also address some of the main challenges faced by implementing cell culture models in IBD research while bearing in mind clinical translational aspects.
Topics: Humans; Inflammatory Bowel Diseases; Colitis, Ulcerative; Crohn Disease; Cell Culture Techniques; Inflammation
PubMed: 38296115
DOI: 10.1016/j.bbadis.2024.167042 -
Clinical Gastroenterology and... Dec 2023The available risk stratification indices for hepatocellular cancer (HCC) have limited applicability. We developed and externally validated an HCC risk stratification...
BACKGROUND & AIMS
The available risk stratification indices for hepatocellular cancer (HCC) have limited applicability. We developed and externally validated an HCC risk stratification index in U.S. cohorts of patients with cirrhosis.
METHODS
We used data from 2 prospective U.S. cohorts to develop the risk index. Patients with cirrhosis were enrolled from 8 centers and followed until development of HCC, death, or December 31, 2021. We identified an optimal set of predictors with the highest discriminatory ability (C-index) for HCC. The predictors were refit using competing risk regression and its predictive performance was evaluated using the area under the receiver-operating characteristic curve (AUROC). External validation was performed in a cohort of 21,550 patients with cirrhosis seen in the U.S Veterans Affairs system between 2018 and 2019 with follow-up through 2021.
RESULTS
We developed the model in 2431 patients (mean age 60 years, 31% women, 24% cured hepatitis C, 16% alcoholic liver disease, and 29% nonalcoholic fatty liver disease). The selected model had a C-index of 0.77 (95% confidence interval [CI], 0.73-0.81), and the predictors were age, sex, smoking, alcohol use, body mass index, etiology, α-fetoprotein, albumin, alanine aminotransferase, and platelet levels. The AUROCs were 0.75 (95% CI, 0.65-0.85) at 1 year and 0.77 (95% CI, 0.71-0.83) at 2 years, and the model was well calibrated. In the external validation cohort, the AUROC at 2 years was 0.70 with excellent calibration.
CONCLUSION
The risk index, including objective and routinely available risk factors, can differentiate patients with cirrhosis who will develop HCC and help guide discussions regarding HCC surveillance and prevention. Future studies are needed for additional external validation and refinement of risk stratification.
Topics: Humans; Female; Middle Aged; Male; Liver Neoplasms; Carcinoma, Hepatocellular; Prospective Studies; Liver Cirrhosis; Risk Factors; Risk Assessment
PubMed: 37390101
DOI: 10.1016/j.cgh.2023.04.019 -
Cell Communication and Signaling : CCS Mar 2024Tryptophan (Trp) metabolism plays a crucial role in influencing the development of digestive system tumors. Dysregulation of Trp and its metabolites has been identified... (Review)
Review
Tryptophan (Trp) metabolism plays a crucial role in influencing the development of digestive system tumors. Dysregulation of Trp and its metabolites has been identified in various digestive system cancers, including esophageal, gastric, liver, colorectal, and pancreatic cancers. Aberrantly expressed Trp metabolites are associated with diverse clinical features in digestive system tumors. Moreover, the levels of these metabolites can serve as prognostic indicators and predictors of recurrence risk in patients with digestive system tumors. Trp metabolites exert their influence on tumor growth and metastasis through multiple mechanisms, including immune evasion, angiogenesis promotion, and drug resistance enhancement. Suppressing the expression of key enzymes in Trp metabolism can reduce the accumulation of these metabolites, effectively impacting their role in the promotion of tumor progression and metastasis. Strategies targeting Trp metabolism through specific enzyme inhibitors or tailored drugs exhibit considerable promise in enhancing therapeutic outcomes for digestive system tumors. In addition, integrating these approaches with immunotherapy holds the potential to further enhance treatment efficacy.
Topics: Humans; Tryptophan; Gastrointestinal Neoplasms; Liver
PubMed: 38462620
DOI: 10.1186/s12964-024-01552-7 -
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 -
Frontiers in Immunology 2023The brain-gut axis link has attracted increasing attention, with observational studies suggesting that the relationship between common mental disorders and inflammatory...
BACKGROUND
The brain-gut axis link has attracted increasing attention, with observational studies suggesting that the relationship between common mental disorders and inflammatory bowel disease (IBD) may run in both directions. However, so far, it is not clear whether there is causality and in which direction.
METHODS
We conducted a bidirectional 2-sample Mendelian randomization study to investigate the relationship between IBD, including Crohn's disease (CD) and ulcerative colitis (UC), and mental disorders, using summary-level GWAS data. The main analysis was the inverse variance weighted method. IBD (including CD and UC), and nine mental disorders were used as both exposures and outcomes.
RESULTS
We found that UC could significantly lead to obsessive-compulsive disorder, attention deficit hyperactivity disorder, and autism spectrum disorder, with odds ratio (OR) of 1.245 (95% confidence intervals [CI]: 1.069-1.450; =0.008), 1.050 (95%CI: 1.023-1.077; =2.42×10), and 1.041 (95%CI: 1.015-1.068; =0.002) respectively. In addition, we found that bipolar disorder and schizophrenia could increase the odds of IBD, with OR values of 1.138 (95%CI: 1.084-1.194; =1.9×10), and 1.115 (95%CI: 1.071-1.161; =1.12×10), respectively. Our results also indicate that obsessive-compulsive disorder could lead to IBD, especially for UC, with OR values of 1.091 (95%CI: 1.024-1.162; =0.009), and 1.124 (95%CI: 1.041-1.214; =0.004), respectively.
CONCLUSIONS
Our findings indicate that the brain-gut axis involves the association between IBD, especially UC, and some mental disorders, which guides the targeted prevention, management, and mechanism exploration of these diseases.
Topics: Humans; Autism Spectrum Disorder; Mendelian Randomization Analysis; Inflammatory Bowel Diseases; Mental Disorders; Colitis, Ulcerative; Crohn Disease; Ascomycota
PubMed: 37901213
DOI: 10.3389/fimmu.2023.1267834 -
Annals of Hepatology 2024The Baveno VII consensus workshop has provided several novel recommendations regarding the management of patients with clinically significant portal hypertension (CSPH).... (Review)
Review
The Baveno VII consensus workshop has provided several novel recommendations regarding the management of patients with clinically significant portal hypertension (CSPH). The expert panel summarized the existing data into simple clinical rules to aid clinicians in their clinical practice. The use of non-invasive tests (NITs), especially liver stiffness measurement (LSM), have gain an important role in daily practice. The use of LSM alone or in combination with platelet count can be used to rule-in and rule-out compensated advanced chronic liver disease (cACLD) and CSPH. Further decompensation events were defined as a prognostic stage associated with an even higher mortality than that associated with first decompensation. Moreover, the term hepatic recompensation was introduced in Baveno VII consensus implying a partial or complete regression of the functional and structural changes of cirrhosis after the removal of the underlying etiology. This review will summarize the reader main aspects of Baveno VII consensus regarding the use of NITs in cACLD, analyze further decompensation events, and evaluate recent recommendations for prophylaxis and management of liver decompensation events.
Topics: Humans; Esophageal and Gastric Varices; Hypertension, Portal; Liver Cirrhosis; Prognosis; Elasticity Imaging Techniques
PubMed: 37984701
DOI: 10.1016/j.aohep.2023.101180 -
Annals of Hepatology 2023Non-alcoholic fatty liver disease (NAFLD) represents a global public health burden. Despite the increase in its prevalence, the disease has not received sufficient... (Review)
Review
Non-alcoholic fatty liver disease (NAFLD) represents a global public health burden. Despite the increase in its prevalence, the disease has not received sufficient attention compared to the associated diseases such as diabetes mellitus and obesity. In 2020 it was proposed to rename NAFLD to metabolic dysfunction-associated fatty liver disease (MAFLD) in order to recognize the metabolic risk factors and the complex pathophysiological mechanisms associated with its development. Furthermore, along with the implementation of the proposed diagnostic criteria, the aim is to address the whole clinical spectrum of the disease, regardless of BMI and the presence of other hepatic comorbidities. As would it be expected with such a paradigm shift, differing viewpoints have emerged regarding the benefits and disadvantages of renaming fatty liver disease. The following review aims to describe the way to the MAFLD from a historical, pathophysiological and clinical perspective in order to highlight why MAFLD is the approach to follow.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Risk Factors
PubMed: 37468095
DOI: 10.1016/j.aohep.2023.101138 -
The Korean Journal of Gastroenterology... Mar 2024Obesity increases gastroesophageal reflux disease through several factors. As a result, Barrett's esophagus, esophageal adenocarcinoma, and gastroesophageal junctional... (Review)
Review
Obesity increases gastroesophageal reflux disease through several factors. As a result, Barrett's esophagus, esophageal adenocarcinoma, and gastroesophageal junctional gastric cancer are increasing. Existing studies usually defined obesity by body mass index and analyzed the correlation. Recently, more studies have shown that central obesity is a more important variable in upper gastrointestinal diseases related to gastroesophageal reflux. Studies have reported that weight loss is effective in reducing gastroesophageal reflux symptoms. Obesity also affects functional gastrointestinal diseases. A significant correlation was shown in upper abdominal pain, reflux, vomiting, and diarrhea rather than lower abdominal diseases.
Topics: Humans; Barrett Esophagus; Esophageal Neoplasms; Gastroesophageal Reflux; Adenocarcinoma; Esophagitis, Peptic; Obesity
PubMed: 38522850
DOI: 10.4166/kjg.2024.015