Translational gastroenterology and hepatology最新文献

Background: Acute pancreatitis (AP) is a complex inflammatory condition with rising incidence globally. Despite various known causes, early diagnosis remains challenging due to limitations in existing biomarkers. Metabolomics offers a promising avenue for identifying novel biomarkers and elucidating underlying pathophysiological mechanisms. Previous AP metabolomics studies primarily focused on analyzing serum, urine, and pancreatic tissues from patients or animal models. However, systematic metabolomics studies that analyze multiple tissues simultaneously are still lacking. The primary aim of our study is to obtain valuable clues to explore the pathophysiological mechanisms of AP and discover novel biomarkers to enable early detection.

Methods: Using a mouse model of AP induced by cerulein, we conducted gas chromatography-mass spectrometry (GC-MS) metabolomic analysis on serum, pancreas, liver, spleen, colon, and kidney samples. Twelve male C57BL/6J mice were randomly divided into AP and control (CON) groups. Serum and tissue samples were collected, processed, and analyzed using established protocols. Multivariate statistical analysis was employed to identify differential metabolites and impacted metabolic pathways.

Results: Distinct metabolic profiles were observed between AP and CON groups across multiple tissues. Elevated levels of ketone bodies, amino acids, citric acid, and lipids were noted, with significant differences in metabolite levels identified. Notably, 3-hydroxybutyric acid (3-HBA), branched-chain amino acids (BCAAs), phenylalanine, and L-lysine showed consistent alterations, suggesting their potential as early diagnostic biomarkers for AP. Pathway analysis revealed perturbations in several metabolic pathways, providing insights into the pathophysiological mechanisms underlying AP.

Conclusions: Our study highlights the utility of metabolomics in identifying potential biomarkers for early diagnosis of AP and elucidating associated metabolic pathways. 3-HBA, BCAAs, phenylalanine and L-lysine emerge as promising biomarkers for further clinical validation. These findings contribute to a better understanding of AP pathophysiology and underscore the potential of metabolomics in precision medicine approaches for AP management.

Background and objective: Complementary and integrative health (CIH) approaches are increasingly popular among patients with gastrointestinal (GI) disorders. Whole person health has been identified as an important perspective in integrative health. While complementary approaches have been discussed in the GI literature, the whole person health framework has not yet been incorporated. Whole person health is particularly relevant as we shift to patient-centered care to facilitate holistic healing for this population. The aim of this paper is to apply a conceptualization of whole person health and its relevance in understanding how CIH approaches can be utilized for patients with stress-sensitive GI disorders, such as disorders of gut-brain interaction (DGBI) and inflammatory bowel disease (IBD).

Methods: Between July 2023 and December 2023 numerous major databases were reviewed to identify relevant articles for this narrative review. Keywords searched included (but not limited to) complementary alternative medicine, integrative medicine, DGBI, IBD, whole person health, and CIH categories (nutritional, mind-body, psychological). We limited our search to peer-reviewed English language articles. Studies were also cross-referenced to incorporate additional relevant studies.

Key content and findings: This narrative review describes how to integrate CIH approaches with whole person health for patients with some of the most common stress-sensitive GI disorders, including DGBIs and IBD. In each section, we highlight how each domain of the whole person health framework (biological, behavioral, social, environmental) can be addressed through CIH approaches: psychological, mind-body practices, and nutritional.

Conclusions: The integration of CIH approaches into the treatment of GI disorders is a growing area of interest that holds promise for enhancing patient outcomes. The two concepts of CIH and whole person health are harmonizing, and their integration serves to support patients who are already using CIH approaches, and providers who can facilitate shared-decision-making and patient-centered care. While not exhaustive, this review demonstrates positive associations between the use of CIH and beneficial outcomes across all whole person health domains for patients with GI disorders.

Background and objective: The study of resilience in youth with inflammatory bowel disease (IBD) is in early stages. The current review aims to illustrate how the use of a multisystemic framework may serve as a developmental and disease-appropriate framework for conceptualizing and designing resilience research for youth with IBD.

Methods: This is a narrative review; therefore, a comprehensive and systematic literature search was not conducted. Rather, the current paper aims to map selected existing literature to a multisystemic model as exemplars of how the model may be used in youth with IBD. Relevant literature was reviewed, synthesized, and mapped onto the proposed multi-systemic framework.

Key content and findings: The current review considers existing literature across three proposed dimensions of resilience: contexts of risk exposure, protective and promotive factors/processes, and desired outcomes. Review of each dimension includes consideration of selected existing literature to explain what is known about each dimension currently, as well as to propose additional potential future areas to broaden understanding. Specific key takeaways include: (I) understanding risk exposure in young people with IBD requires consideration of disease-specific, demographic, and sociocultural factors; (II) protective and promotive factors and processes for these young people span individual, familial, peer, school, and community levels; and (III) desired outcomes encompass both the absence of negative and the presence of positive indicators.

Conclusions: A multisystemic approach to the study of resilience in young people with IBD may not only clarify current gaps in the field, but also allow for additional future considerations to best understand how and for whom outcomes characterized as resilient may occur in this population.

Background: Diabetes mellitus (DM) is associated with the increased risk of development and the advancement of cholangiocarcinoma (CCA). High glucose levels were previously shown for upregulating interleukin-1β (IL-1β) in CCA cells with unclear functions. The present study, thus, aimed to investigate molecular mechanisms linking DM to CCA progression, with IL-1β hypothesized as a communicating cytokine.

Methods: CCA cells were cultured in media with normal (5.6 mM) or high (25 mM) glucose, resembling euglycemia and hyperglycemia, respectively. Expressions of IL-1β and IL-1 receptor (IL-1R) in CCA tissues from patients with and without DM were examined using immunohistochemistry. Functional analyses of IL-1β were performed using siRNA and recombinant human IL-1R antagonist (rhIL-1RA), in which Western blots investigated the knockdown efficacy. BALB/c Rag-2^-/- Jak3^-/- (BRJ) mice were implanted with CCA xenografts to investigate hyperglycemia's effects on CCA growth and the anti-tumor effects of IL-1RA.

Results: CCA tumors from patients with hyperglycemia showed significantly higher IL-1β expression than those from non-DM patients, while IL-1β was positively correlated with fasting blood glucose (FBG) levels. CCA cells cultured in high glucose showed increased IL-1β expression, resulting in increased proliferation rates. Suppressing IL-1β signaling by si-IL-1β or rhIL-1RA significantly reduced CCA cell proliferation in vitro. Anakinra, a synthetic IL-1RA, also exerted significant anti-tumor effects in vivo and significantly reversed the effects of hyperglycemia-induced growth in CCA xenografts.

Conclusions: IL-1β plays a crucial role in CCA progression in a high-glucose environment. Targeting IL-1β might, then, help improve therapeutic outcomes of CCA in patients with DM and hyperglycemia.

Successful multichannel intraluminal impedance and pH monitoring (MII-pHM) studies rely on constant attendants (CAs) or family members (and sometimes the patients themselves) to assist in the execution and facilitation of the MII-pHM study. While "pushing buttons" [corresponding to specific symptoms, body position (upright versus recumbent), and meal start and stop times] on the MII-pHM system recording box is indeed a big part of MII-pHM study execution and facilitation, there are other concerns and duties that are equally as important. This paper outlines some of the important duties of the study facilitator (or patient) during a MII-pHM study. When provided with the proper training, study facilitators invigilating the MII-pHM study will be better able to contribute to the data collection process and ultimately to produce data that when analyzed will lead to better interpretations, clinical recommendations, and good clinical outcomes. When executed properly, MII-pHM studies have the potential to assess diurnal exposure of the esophageal mucosa to gastric/duodenal contents, provide insight regarding the proximal extent of gastroesophageal reflux (GER), provide a measurement of the mean esophageal pH, and assess mucosal integrity and temporal relationship between GER and the symptoms of interest. While several groups have offered recommendations for proper execution of the MII-pHM study, to our knowledge, there have not been publications wherein recommendations were compiled to form a single source document.

Background: Liver transplantation (LT) is the best treatment for end-stage liver disease; however, biliary complications (BCs) still pose a significant challenge. Among the post-transplant BC, strictures and biliary fistulas are the most common. Biliary strictures are classified as anastomotic and non-anastomotic. Some previous studies suggest an association between post-transplant biliary strictures and cytomegalovirus (CMV) infection. In this study, we aimed to identify whether there is an association between CMV infection and biliary strictures in patients undergoing LT.

Methods: A retrospective study of 175 patients aged ≥18 years undergoing LT at Felicio Rocho Hospital between 2011 and 2017 was conducted. All included patients received grafts perfused with Institut Georges Lopez-1 (IGL-1) solution from brain-dead donors, survived post-transplantation for more than 120 days, and had a minimum follow-up of 12 months after LT. The diagnosis of CMV was made by antigenemia and biliary strictures by magnetic resonance cholangiopancreatography (MRCP).

Results: The average age of the recipients was 54 years. Postoperative BCs occurred in 12% of transplants. The most common BC was stricture (9.1%), with a predominance of anastomotic strictures (AS) over non-AS (NAS) (87.5% vs. 12.5%, respectively). CMV infection was confirmed in 22.9% of patients. In the univariate analysis, post-transplant CMV infection correlated with the development of BCs (P=0.01), as well as biliary strictures (P=0.008). In the multivariate analysis, however, only model for end-stage liver disease (MELD) >21 was a risk factor for the development of BCs in general (P=0.02) and biliary strictures (P=0.01).

Conclusions: CMV infection was not an independent risk factor for the development of non-anastomotic post-transplant biliary strictures in this study.

Background: Connective tissue diseases (CTDs) are characterized by immune system dysregulation, which can profoundly impact the gastrointestinal (GI) system. While GI bleeding is a well-recognized cause of mortality and morbidity in the USA, its occurrence in patients with CTD remains documented but underexplored in terms of inpatient outcomes. GI bleeding in CTD is attributed to factors such as vasculopathy and drug-related risks, notably steroids and non-steroidal anti-inflammatory drugs (NSAIDs). This research seeks to conduct a comprehensive national-level analysis, utilizing the National Inpatient Sample (NIS), to compare GI bleeding outcomes between patients with CTD and those without this condition.

Methods: Utilizing the extensive NIS database covering 2020, we conducted a retrospective analysis of GI bleeding patients with CTD, identified through the International Classification of Diseases, 10^th Revision (ICD-10). The primary outcome was in-hospital mortality. The secondary outcomes included rate of urgent esophagogastroduodenoscopy (EGD) and colonoscopy-endoscopy in 1 day or less, total rate of EGD and colonoscopy, rate of EGD and Colonoscopy with intervention, rate of complications including acute kidney injury (AKI), blood transfusion, sepsis, pneumonia, pulmonary embolism (PE) and healthcare utilization. Employing Stata software, we utilized multivariate logistic and linear regression analyses to adjust for confounders.

Results: There were 455,494 hospitalizations for GI bleeding and 19,874 involved patients with CTDs. The in-hospital mortality rate was significantly lower for CTD patients at 2.1%, compared to 2.4% for non-CTD patients [adjusted odds ratio (aOR): 0.79, 95% confidence interval (CI): 0.63-0.99, P=0.04]. CTD patients showed increased odds of total EGD, urgent colonoscopy, and total colonoscopy; however, these changes were not statistically significant. CTD patients had higher odds of complications, including PE (6.87% vs. 4.12%, P=0.009). However, there were no significant differences in mean length of hospital stay and total hospital charges (THCs) compared to non-CTD patients.

Conclusions: Patients with CTD exhibited a lower in-hospital mortality rate compared to those without CTD. The elevated risk of PE underscores the importance of implementing prophylactic measures for these patients.