Introduction: The association between Helicobacter pylori (H. pylori) infection and digestive autoimmune diseases remains unclear, with inconsistent findings in previous observational studies. We conducted Mendelian randomization (MR) analysis to systematically explore the causal relationship and delve into the pathogenesis based on gut microbiota. Methods: This study encompassed anti-H. pylori IgG levels and genome-wide association studies (GWASs) for multiple digestive autoimmune diseases, utilizing diverse MR methodologies to assess the causal relationship between H. pylori antibody levels and these diseases. Associations between H. pylori and ulcerative colitis (UC) were examined using genetic variants from MiBioGen associated with 194 gut microbiota traits. Additionally, a series of sensitivity analyses were performed to validate the results of the initial MR analyses. Results: Our study showed a significant association between anti-H. pylori IgG levels and the incidence risk of UC (β = −0.001, p = 0.011). No causal associations were observed with the incidence risk of primary biliary cirrhosis, primary sclerosing cholangitis, celiac disease, and Crohn’s disease (CD). Multiple gut microbiota were found to be correlated with H. pylori infection and UC. Particularly noteworthy is the negative correlation between the abundance of the genus.Anaerofilum and H. pylori antibody levels (β = −0.174, p = 0.048). Notably, genus.Anaerofilum exhibited a positive genetic correlation with an increased risk of UC (β = 0.0014, p = 0.0029). Conclusion: MR analysis confirmed a causal association between anti-H. pylori IgG and UC, but not with CD. The genus.Anaerofilum may increase the risk of UC by inhibiting H. pylori infection.
Niloofar Mirzadzare, Graham A. D. Blyth, Rita Hannawayya
et al.
Colonic goblet cells play a crucial role in mucosal defense by secreting Muc2 mucin and other proteins that entrap and expel enteropathogens. However, the role of innate effectors in the gut like cathelicidin peptides in regulating the mucus barrier during infections remains unclear. In this study, we used cathelicidin-deficient (Camp-/-) littermates, colonoids, and human LS174T goblet-like cells to investigate how cathelicidin modulates goblet cell function and mucosal defense against attaching/effacing enteropathogen Citrobacter rodentium. We showed that increased fecal shedding and epithelial colonization by C. rodentium in Camp-/- littermates was accompanied by impaired mucus secretion and higher retention of mucin granules and trefoil factor 3 (Tff3) in bloated colonic goblet cells. Reduction in mucus secretion by goblet cells was accompanied by reduced reactive oxygen species (ROS) production during C. rodentium infection in Camp-/- as compared to Camp+/+ littermate controls. In LS174T goblet-like cells, human cathelicidin LL-37 stimulated the secretion of TFF3 and resistin-like molecule β (RELMβ) in a ROS-dependent manner. These findings reveal that cathelicidin regulates goblet cell mucus and mucus-associated protein secretion through a ROS-mediated mechanism critical for bacterial clearance and maintenance of gut homeostasis.
Diseases of the digestive system. Gastroenterology
Konstantinos Papantoniou, Christos Michailides, Dimitrios Velissaris
et al.
The management of antithrombotic agents in patients undergoing urgent gastrointestinal (GI) endoscopy presents a common and complex clinical challenge. The use of anticoagulants and antiplatelet therapies, especially in older patients with significant comorbidities, has increased substantially in recent decades due to the rising prevalence of cardiovascular and thromboembolic diseases. Balancing the risk of ongoing hemorrhage against the potentially life-threatening consequences of thrombosis remains a delicate and critical clinical decision. This review provides a practical, evidence-based approach to the periprocedural management of antithrombotic therapy in urgent endoscopy, particularly in the context of acute GI bleeding. We summarize the indications, pharmacokinetics, and reversal strategies for commonly used agents, including warfarin, direct oral anticoagulants (DOACs), low-molecular-weight heparin, aspirin, and P2Y12 inhibitors. Risk stratification is discussed in detail, considering both the urgency and bleeding risk of endoscopic procedures, as well as the thromboembolic risk associated with temporary drug interruption. Special considerations are given to high-risk patients, such as those with recent coronary stents, mechanical heart valves, or atrial fibrillation with elevated stroke risk scores. Close consultation and collaboration with other specialties, including cardiology and hematology, is often essential to optimize patient outcomes. Recommendations based on real-world clinical experience alongside formal guideline directives aim to support safe and timely endoscopic intervention without compromising systemic thrombotic protection, especially in emergent situations.
Diseases of the digestive system. Gastroenterology
Introduction
The aim of this study was to analyse the effect of perioperative dexmedetomidine (DEX) application on stress response, post-operative pain and prognosis in patients undergoing gynaecologic laparoscopy.
Patients and Methods
One hundred and sixty-eight patients admitted for gynaecologic laparoscopic surgery from May 2020 to November 2022 were included in the study. The patients were randomly divided into pre-operative DEX group (n = 56), intraoperative DEX group (n = 56) and post-operative DEX group (n = 56) according to the application of DEX in the perioperative period. The visual analogue scale (VAS), time awake, extubation time, pneumoperitoneum time, post-anaesthesia care unit (PACU) stay time and Richmond agitation-sedation scale score (RASS) were recorded.
Results
Patients in both the pre-operative and intraoperative DEX groups had substantially shorter wakeup and extubation times than those in the post-operative DEX group. Patients in the pre-operative DEX group had considerably shorter wakeup and extubation times than those in the intraoperative DEX group, and their pneumoperitoneum time was significantly shorter than that of the post-operative DEX group (P < 0.001). The RASS scores of the pre-operative DEX group and intraoperative DEX group were significantly lower than those of the post-operative DEX group at 1 h, 6 h and 12 h after surgery. Meanwhile, at all time periods, the RASS scores of patients in the pre-operative DEX group were considerably lower than those in the intraoperative DEX group (P < 0.01). The VAS scores of patients in the pre-operative DEX group and intraoperative DEX group were evidently lower than those in the post-operative DEX group at 0.5 h, 2 h and 12 h postoperatively, and the VAS scores of patients in the pre-operative DEX group were markedly lower than those in the intraoperative DEX group (P < 0.001). The incidence of nausea and vomiting was significantly lower in the pre-operative DEX group than in the intraoperative DEX group and the post-operative DEX group at 0–2 h, >2–12 h and >12–24 h postoperatively (P < 0.001). The incidence of nausea and vomiting in the intraoperative DEX group was significantly lower than that in the post-operative DEX group from 0 to 2 h after surgery (P < 0.05). The incidence of adverse reactions was not significantly different amongst the three groups of patients (P > 0.05).
Conclusion
Pre-operative and intraoperative application of DEX can help reduce post-operative pain and stress responses, help patients recover quickly after surgery and improve patient prognosis, especially the pre-operative application of DEX.
Surgery, Diseases of the digestive system. Gastroenterology
Mehmet Tahtacı, Emre Yıldırım, Enver Üçbilek
et al.
Background/Aims: Gastroenterologists have an important role in the treatment and management of comorbidities related to obesity. Assessment of gastroenterologists’ perception and attitude toward obesity was aimed in this study.
Materials and Methods: Survey questions were determined for the study. An online questionnaire was prepared afterward. Participants were invited via e-mail by providing them with information about the study. It was ensured that those who accepted the study could access the questionnaire form with the relevant link. Participants who answered all questions were included in the study.
Results: Totally 117 gastroenterologists were included in the study. The proportion of gastroenterologists who thought that obesity complicates the management of gastroenterological diseases and those who thought obesity as a factor that negatively affects the prognosis of gastroenterological diseases was determined as 88.9% and 95.7%, respectively. Among the obese patients, the proportion of those who applied diet therapy, exercise, pharmacotherapy, and endoscopic methods was 94%, 91.5%, 35%, and 37.6%, respectively. The rates of intragastric balloon therapy and intragastric botulinum toxin A injection were 30% and 21.4%, respectively. The proportion of those who agreed that obese patients lost a significant amount of weight with the treatment methods applied was 47.2%. The proportion of participants who agreed that long-term maintenance of weight loss was impossible for most obese patients was 59.8%.
Conclusion: To our knowledge, this is the first study that evaluates the perception and attitude of gastroenterologists toward obesity. Our study results show that gastroenterologists think that obesity is a chronic disease and that gastroenterologists should be involved in management of obesity.
Diseases of the digestive system. Gastroenterology
Tadataka Takagi, Fumikazu Koyama, Hiroyuki Kuge
et al.
Objectives: This study aimed to investigate the impact of the COVID-19 pandemic on the examination and treatment of colorectal cancer (CRC) and on the behaviors of patients and practitioners.
Methods: This is a retrospective analysis of the CRC patients who presented to our department between April 2019 and March 2021 and underwent surgery. Clinical presentation of CRC and time from symptom onset to medical presentation were compared between the control (April 2019 to March 2020, n=124) and COVID-19 pandemic periods (April 2020 to March 2021, n=111).
Results: Two hundred and thirty-five patients were reviewed. The rate of positive fecal occult blood tests was significantly lower during the COVID-19 pandemic period (13.5 vs. 25.0%, P = 0.027). Among the symptomatic patients who had melena and abdominal symptoms, the time from symptom onset to medical presentation was significantly longer during the COVID-19 period (115 vs. 31 days, P < 0.001). In addition, the interval between presenting to a practitioner and being referred to our department was similar between the two periods (19 vs. 13 days, P = 0.092). There were no significant differences in the stage of cancer between the two periods. The rate of preoperative sub-obstruction was significantly higher during the COVID-19 period (41.4 vs 23.4%, P = 0.003). There was no significant difference in overall survival and recurrence-free survival between two periods.
Conclusions: Hesitation to seek examination and treatment for CRC was observed in patients but not in practitioners during the COVID-19 pandemic period. The prognosis did not change.
Diseases of the digestive system. Gastroenterology
Jonatan C. S. de Carvalho, P. V. da Silva-Neto, D. M. Toro
et al.
COVID-19 is associated with a dysregulated immune response. Currently, several medicines are licensed for the treatment of this disease. Due to their significant role in inhibiting pro-inflammatory cytokines and lipid mediators, glucocorticoids (GCs) have attracted a great deal of attention. Similarly, the endocannabinoid (eCB) system regulates various physiological processes including the immunological response. Additionally, during inflammatory and thrombotic processes, phospholipids from cell membranes are cleaved to produce platelet-activating factor (PAF), another lipid mediator. Nonetheless, the effect of GCs on this lipid pathway during COVID-19 therapy is still unknown. This is a cross-sectional study involving COVID-19 patients (n = 200) and healthy controls (n = 35). Target tandem mass spectrometry of plasma lipid mediators demonstrated that COVID-19 severity affected eCBs and PAF synthesis. This increased synthesis of eCB was adversely linked with systemic inflammatory markers IL-6 and sTREM-1 levels and neutrophil counts. The use of GCs altered these lipid pathways by reducing PAF and increasing 2-AG production. Corroborating this, transcriptome analysis of GC-treated patients blood leukocytes showed differential modulation of monoacylglycerol lipase and phospholipase A2 gene expression. Altogether, these findings offer a breakthrough in our understanding of COVID-19 pathophysiology, indicating that GCs may promote additional protective pharmacological effects by influencing the eCB and PAF pathways involved in the disease course.
Background: Congenital portosystemic shunts (CPSS) are rare vascular anomalies resulting in communications between the portal venous system and the systemic venous circulation, affecting an estimated 30,000 to 50,000 live births. CPSS can present at any age as a multi-system disease of variable severity mimicking both common and rare pediatric conditions. Case presentations: Case A: A vascular malformation was identified in the liver of a 10-year-old girl with tall stature, advanced somatic maturation, insulin resistance with hyperinsulinemia, hyperandrogenemia and transient hematuria. Work-up also suggested elevated pulmonary pressures. Case B: A young girl with trisomy 8 mosaicism with a history of neonatal hypoglycemia, transient neonatal cholestasis and tall stature presented newly increased aminotransferase levels at 6 years of age. Case C: A 3-year-old boy with speech delay, tall stature and abdominal pain underwent abdominal ultrasound (US) showing multiple liver nodules, diagnosed as liver hemangiomas by hepatic magnetic resonance imaging (MRI). Management and outcome: After identification of a venous malformation on liver Doppler US, all three patients were referred to a specialized liver center for further work-up within 12 to 18 months from diagnosis. Angio-computed tomography (CT) scan confirmed the presence of either an intrahepatic or extrahepatic CPSS with multiples liver nodules. All three had a hyperintense signal in the globus pallidus on T1 weighted cerebral MRI. Right heart catheterization confirmed pulmonary hypertension in cases A and C. Shunts were closed either using an endovascular or surgical approach. Liver nodules were either surgically removed if there was a risk of malignant degeneration or closely monitored by serial imaging when benign. Conclusion: These cases illustrate most of the common chief complaints and manifestations of CPSS. Liver Doppler US is the key to diagnosis. Considering portosystemic shunts in the diagnostic work-up of a patient with unexplained endocrine, liver, gastro-intestinal, cardiovascular, hematological, renal or neurocognitive disorder is important as prompt referral to a specialized center may significantly impact patient outcome.
Chinese Society of Gastroenterology, Cancer Collaboration Group of Chinese Society of Gastroenterology, Chinese Medical Association
Most patients with colorectal cancer (CRC) were diagnosed in advanced stage and the prognosis is poor. Therefore, early detection and prevention of CRC are very important. As with other cancers, there is also the tertiary prevention for CRC. The primary prevention is etiological prevention, which is mainly the treatment of adenoma or inflammation for preventing the development into cancer. The secondary prevention is the early diagnosis and early treatment for avoiding progressing to advanced cancer. The tertiary prevention belongs to the broad category of prevention, mainly for advanced CRC, through surgical treatment and postoperative adjuvant chemotherapy, radiotherapy, targeted therapy, immunotherapy for preventing tumor recurrence or metastasis. This consensus is based on the recent domestic and international consensus guidelines and the latest progress of international researches in the past five years. This consensus opinion seminar was hosted by the Chinese Society of Gastroenterology and Cancer Collaboration Group of Chinese Society of Gastroenterology, and was organized by the Division of Gastroenterology and Hepatology & Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University. The consensus opinion contains 60 statement clauses, the standard and basis of the evidence‐based medicine grade and voting grade of the statement strictly complied with the relevant international regulations and practice.
Background/Aims Patients with acute cholecystitis (AC) after metallic stent (MS) placement for malignant biliary obstruction (MBO) have a high surgical risk. We performed percutaneous transhepatic gallbladder aspiration (PTGBA) as the first treatment for AC. We aimed to identify the risk factors for AC after MS placement and the poor response factors of PTGBA. Methods We enrolled 401 patients who underwent MS placement for MBO between April 2011 and March 2020. The incidence of AC was 10.7%. Of these 43 patients, 37 underwent PTGBA as the first treatment. The patients’ responses to PTGBA were divided into good and poor response groups. Results There were 20 patients in good response group and 17 patients in poor response group. Risk factors for cholecystitis after MS placement included cystic duct obstruction (p<0.001) and covered MS (p<0.001). Cystic duct obstruction (p=0.003) and uncovered MS (p=0.011) demonstrated significantly poor responses to PTGBA. Cystic duct obstruction is a risk factor for cholecystitis and poor response factor for PTGBA, whereas covered MS is a risk factor for cholecystitis and an uncovered MS is a poor response factor of PTGBA for cholecystitis. Conclusions The onset and poor response factors of AC after MS placement were different between covered and uncovered MS. PTGBA can be a viable option for AC after MS placement, especially in patients with covered MS.
Internal medicine, Diseases of the digestive system. Gastroenterology
Nicole Strossman, Katherine Donovan, Alexa Trovato
et al.
Eosinophilic esophagitis (EoE), a chronic inflammatory disease of the esophagus, has been increasing in incidence over the past several years. Mainstays of treatment include dietary modifications, steroids, proton pump inhibitors (PPIs), and endoscopic dilation, with the goal being to control disease progression, promote remission, and alleviate symptoms, such as dysphagia and food impaction. In addition to these well-known treatment options, preliminary studies on new medications that target specific inflammatory mediators involved in the pathogenesis of EoE have shown promise in improving symptoms. This review article summarizes and discusses the application and efficacy of long-standing and promising new treatment options for EoE.
Diseases of the digestive system. Gastroenterology
Abstract Canada has among the highest incidence and prevalence of inflammatory bowel disease (IBD) in the world. After decades of rising incidence of IBD in Canada during the 20th Century, the prevalence of IBD in 2018 is 0.7% of the Canadian population. Forecasting models predict that prevalence of IBD will continue to rise to 1.0% of the population by 2030. In 2018, the number of Canadians living with IBD is approximately 270,000 and is predicted to rise to 403,000 Canadians in 2030. Inflammatory bowel disease affects all age groups with adolescents and young adults at highest risk of diagnosis. Canadians of all ethnicities are being diagnosed with IBD including known high-risk groups such as Ashkenazi Jews and offspring of South Asian immigrants who were previously thought to be low risk. Moreover, IBD has evolved into a global disease with rising incidence in newly industrialized countries in Asia and South America. The causes of IBD remain unsolved; however, the high rates of disease in Western countries and its emergence in newly industrialized countries suggest that environmental factors associated with urbanization, modernization, or Western diets may be pertinent to understanding the pathogenesis of the disease. Highlights 1. Canada continues to have among the highest prevalence of IBD in the world. 2. Today, approximately 270,000 Canadians live with IBD. By 2030 it is estimated that nearly 403,000 Canadians will have a diagnosis of IBD. 3. Inflammatory bowel disease has become a worldwide disease with increasing rates in Asia, Africa, and South America—continents where IBD was rarely diagnosed prior to 1990. 4. The causes of IBD are unknown, but the high rates of disease over the past 60 years in Western countries and the emergence of disease in developing countries suggest that factors associated with urbanization, modernization, or Western diets may be pertinent to understanding the pathogenesis of the disease. 5. Many of the leading hypotheses as to the causes of IBD tie in with alteration of the gut microbiome, the suite of organisms that reside in the bowel and maintain bowel health throughout life. Key Summary Points 1. The incidence (the number of new diagnoses annually) of IBD rose throughout the 20th century in Canada and then stabilized at the turn of the 21st century. 2. The prevalence (the total number of diagnosed persons in the population) of IBD in Canada is among the highest in the world. 3. Today, 270,000 (0.7%, or 7 in 1000) Canadians are estimated to live with IBD. By 2030, that number is expected to rise to 403,000 Canadians (1% or 1 in 100). 4. Inflammatory bowel disease can be diagnosed at any age. However, the age groups that are most likely to be diagnosed are adolescents and young adults from 20 to 30 years of age. 5. Inflammatory bowel disease in Canada affects the lives of Canadians of all ethnicities, including known high-risk groups such as Ashkenazi Jews, and those thought previously to be at low risk, such as first-generation offspring of South Asian immigrants. 6. Canadian health policy makers will need to prepare the Canadian health care system for the rising burden of IBD. 7. As newly industrialized countries in Asia, Africa, and South America are transitioning to a Westernized society, IBD has emerged and its incidence in these countries is rising rapidly. 8. The gut microbiome includes microorganisms that maintain digestive health. Thus, changes in the microbiome, which may change the immune system’s response to triggers, may be important in initiating and perpetuating IBD. 9. A number of factors can alter the gut microbiome and early childhood may be a particularly important time such that breastfeeding, early life diet, use of antibiotics, infections, and other environmental exposures may impact the gut microbiome in such a way that facilitates developing IBD. 10. Smoking is associated with an increased risk and worsening disease course of Crohn’s disease. Quitting smoking is associated with an increased risk of developing ulcerative colitis. Therefore, never initiating smoking can mitigate the risk for IBD. Educational programs aimed at those at-risk for IBD should emphasize the risk of starting to smoke tobacco. 11. Modifying exposure to environmental risk factors associated with the Westernization of society (e.g., Western diet and lifestyles) may provide an avenue for reducing the risk of IBD in Canada and worldwide. Gaps in Knowledge and Future Directions 1. While the incidence of IBD appears to be stabilizing in some regions in Canada, IBD may be occurring more frequently in certain populations such as in children, South Asians, Ashkenazi Jews, and immigrants. Future research should focus on the changing demographics of IBD in Canada. 2. The prevalence of IBD will rise steadily over the next decade. To enable better health care system planning and to respond adequately to the increasing burden of IBD, ongoing surveillance of the epidemiology and health services utilization of IBD in Canada is necessary. 3. Most studies have focused on the mortality associated with IBD. Future research is necessary to assess health-adjusted life expectancy and overall life expectancy for those living with IBD. 4. Analyses of resources, infrastructure, and personnel need to be modeled into the future in order to prepare our health care system for the rising burden of IBD. 5. Research on the interaction between genes, microbes, and our environment will inform our understanding of the pathogenesis of IBD, information necessary to prevent IBD in the future.
Maureen M Leonard, H. Karathia, Meritxell Pujolassos
et al.
Background Celiac disease (CD) is an autoimmune digestive disorder that occurs in genetically susceptible individuals in response to ingesting gluten, a protein found in wheat, rye, and barley. Research shows that genetic predisposition and exposure to gluten are necessary but not sufficient to trigger the development of CD. This suggests that exposure to other environmental stimuli early in life, e.g., cesarean section delivery and exposure to antibiotics or formula feeding, may also play a key role in CD pathogenesis through yet unknown mechanisms. Here, we use multi-omics analysis to investigate how genetic and early environmental risk factors alter the development of the gut microbiota in infants at risk of CD. Results Toward this end, we selected 31 infants from a large-scale prospective birth cohort study of infants with a first-degree relative with CD. We then performed rigorous multivariate association, cross-sectional, and longitudinal analyses using metagenomic and metabolomic data collected at birth, 3 months and 6 months of age to explore the impact of genetic predisposition and environmental risk factors on the gut microbiota composition, function, and metabolome prior to the introduction of trigger (gluten). These analyses revealed several microbial species, functional pathways, and metabolites that are associated with each genetic and environmental risk factor or that are differentially abundant between environmentally exposed and non-exposed infants or between time points. Among our significant findings, we found that cesarean section delivery is associated with a decreased abundance of Bacteroides vulgatus and Bacteroides dorei and of folate biosynthesis pathway and with an increased abundance of hydroxyphenylacetic acid, alterations that are implicated in immune system dysfunction and inflammatory conditions. Additionally, longitudinal analysis revealed that, in infants not exposed to any environmental risk factor, the abundances of Bacteroides uniformis and of metabolite 3-3-hydroxyphenylproprionic acid increase over time, while those for lipoic acid and methane metabolism pathways decrease, patterns that are linked to beneficial immunomodulatory and anti-inflammatory effects. Conclusions Overall, our study provides unprecedented insights into major taxonomic and functional shifts in the developing gut microbiota of infants at risk of CD linking genetic and environmental risk factors to detrimental immunomodulatory and inflammatory effects. Video Abstract
Abstract Locally advanced rectal cancer requires multidisciplinary care. In the United States, most patients are treated with neoadjuvant chemoradiation delivered over 25‐28 days, total mesorectal excision, and 4 months of adjuvant chemotherapy. While effective, this trimodal approach is arduous. Alternative approaches have emerged to streamline treatment without sacrificing oncologic outcomes. These approaches include preoperative chemotherapy with selective use of radiation, short‐course radiotherapy delivered over 5 days, and total neoadjuvant therapy with attempted nonoperative organ‐preserving management (watch and wait). Ongoing trials are assessing the efficacies of these approaches in combination with various risk stratification strategies.
Surgery, Diseases of the digestive system. Gastroenterology