BACKGROUND:Inflammatory bowel disease (IBD) encompasses chronic gastrointestinal disorders that significantly impact patients' quality of life (QoL). While clinical trials support the efficacy and safety of vedolizumab, real-world data linking its effectiveness to QoL-related patient-reported outcomes remain limited. This prospective observational study assessed the effects of 14-week vedolizumab induction therapy on QoL (i.e., fatigue, mood, and sleep disturbances), clinical response, safety, and predictors of response. METHODS:A total of 257 patients with ulcerative colitis (UC; n = 205) and Crohn's disease (CD; n = 52) received 14-week vedolizumab induction therapy. Disease activity, QoL (assessed using the total Inflammatory Bowel Disease Questionnaire [IBDQ]), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-Fatigue]), mood and sleep disturbances (PROMIS Depression and Sleep Disturbance scales), and selected biomarkers were evaluated. Clinical response was assessed using the Mayo score for UC and Crohn's Disease Activity Index (CDAI) score for CD. RESULTS:At Week 14, clinical response was observed in 82% of UC patients and 82.7% of CD patients. Median total IBDQ scores increased by 45.0 points in UC and 31.5 points in CD (p < 0.001). Median prorated FACIT-Fatigue scores increased by 5.0 points in both groups (p < 0.001), while median prorated PROMIS Sleep Disturbance and Depression T-scores decreased (p < 0.05). Improvement in QoL was moderately correlated with clinical response (r = 0.5). In logistic regression analysis, baseline patient characteristics indicative of advanced disease were associated with a reduced likelihood of clinical and QoL response to treatment. A total of 28 adverse events were reported, including 11 serious events and four treatment-related events. CONCLUSIONS:Vedolizumab reduced disease activity and led to a rapid improvement in QoL during the 14-week induction therapy in patients with IBD. Clinical response was positively correlated with QoL improvement. Predictors of reduced response were consistent with features of advanced disease.
BACKGROUND:Upper gastrointestinal bleeding (UGIB) is a significant cause of cirrhosis decompensation; however, there is still controversy on risk factors for poor outcomes. This study aims to explore the impact of additional variables, such as liver disease etiology and intensive care unit (ICU) accessibility, on mortality, rebleeding, and infection rates. METHODS:Cox regression analysis was employed to identify predictors associated with mortality and rebleeding, while Poisson regression analysis was utilized to assess associations with infections. RESULTS:A total of 228 patients were included, with the majority classified as Child-Pugh B and C. Among them, 96 patients (42.1%) had alcohol-associated liver disease (ALD), of which 45 (46.9%) were in alcohol abstinence. One hundred and ninety-five patients (85.5%) survived, while 33 (14.5%) died. Intubation was required for 31 patients (13.6%), and 28 were transferred to the ICU. Antibiotic prophylaxis was administered to 219 patients (96%), and 55 (24.1%) developed infections. Both orotracheal intubation and transfusions were associated with high mortality, whereas ALD was linked to a lower risk of death (p < 0.001, 0.029, and 0.005, respectively). Intubation was also correlated with an increased risk of rebleeding, while transfer to ICU reduced this complication (p = 0.012 and 0.045, respectively). The Child-Pugh score and length of hospitalization were associated with the occurrence of infections (p = 0.037 and < 0.001, respectively). CONCLUSIONS:Intubation, transfusions, liver disease etiology, and ICU accessibility are critical predictors following UGIB in cirrhosis. Additionally, the Child-Pugh score and duration of hospitalization are directly proportional to the risk of infections in this context. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT04662918.
BackgroundMetabolic dysfunction-associated steatohepatitis (MASH), the progressive phenotype of metabolic dysfunction-associated steatotic liver disease (MASLD), is well recognized for its increased risk of progressing to cirrhosis and hepatocellular carcinoma (HCC). However, early diagnosis and identification of the MASH patients with a tendency toward malignancy HCC remain a significant challenge.MethodIn previous studies, we established a novel conditional inducible HRAS gene expression murine model with normal diet and lifestyle conditions, which exhibited 100% HCC incidence and recapitulated the four major progression stages of MASH to HCC: MASH, fibrosis, cirrhosis, and HCC. Based on this model, we revealed the potential markers of MASH prone to HCC characteristics of malignant MASH through RNA-Seq and bioinformatics analysis, and further confirmed by pathological biopsy, biochemical tests, inflammatory cytokines measurement, Oil O red staining, and immunohistochemical examination.ResultsFor MASH, the initial stage of HCC, we observed evidence of hyperlipidemia and insulin resistance in the HRAS mouse model based on blood morphology, biochemical parameters, and insulin tolerance test. Furthermore, the pathological features of MASH were confirmed by the presence of hepatocellular fatty vacuolar changes, lipid droplet accumulation, and inflammation. Then, RNA-Seq analysis revealed the molecular signatures of malignant MASH and revealed three novel potential markers associated with adverse progression of MASH to HCC: Klk1b4, Alox5, and Pla2g2e.ConclusionBased on a stable and novel murine model of MASH prone to HCC, we, for the first time, presented a comprehensive molecular signature and identified novel potential adverse progression markers of MASH prone to malignant HCC, which contributed possibly to early clinical diagnosis and prognostic assessment, even becoming potential therapeutic target.
Background and Aim: Since the stage of liver fibrosis is closely associated with mortality in nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated steatotic liver disease (MASLD), it is essential to identify patients at risk of fibrosis progression. Basal metabolic rate (BMR) has gained attention in weight management for individuals with obesity. This study aimed to assess the accuracy of BMR in predicting the severity of fibrosis in patients with NAFLD or MASLD. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) 2017-2020.03 were analyzed. Noninvasive diagnosis of liver steatosis was performed using the controlled attenuation parameter (CAP) measured by FibroScan. BMR calculated using the Harris-Benedict equation (BMRh) and the Mifflin-St Jeor equation (BMRm) was included in the analysis. Results: A total of 4184 individuals with MASLD were included, of whom 639 (15.27%) had significant fibrosis. Among 1577 individuals with NAFLD, 223 (14.14%) had significant fibrosis. Participants with significant fibrosis were older and had higher CAP, BMRh, and BMRm values (all p < 0.05). Multivariate analysis identified BMR as an independent risk factor for significant fibrosis. In obesity participants with MASLD or NAFLD, both BMRh and BMRm were positively correlated with BMI, CAP, and liver stiffness measurement (all p < 0.01). For obesity participants with MASLD or NAFLD, both BMRh- or BMRm-incorporating models had higher AUROCs than aspartate transaminase-to-platelet ratio index, fibrosis-4, and gamma-glutamyl transpeptidase to platelet ratio in predicting significant fibrosis (all p < 0.001). Conclusion: BMR is elevated in individuals with NAFLD or MASLD and significant liver fibrosis. The novel model combining age, male gender, BMR, aspartate transaminase, white blood cell counts, platelet counts, and diabetes outperformed conventional noninvasive scoring systems in predicting significant fibrosis in individuals with MASLD and obesity.
BACKGROUND AND AIMS:Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent, and smoking is associated with greater disease severity. We investigated whether documented smoking cessation attempts among adults with MASLD were associated with liver-related outcomes, cardiovascular outcomes, and all-cause mortality. METHODS:We performed a retrospective cohort study using the TriNetX Research Network. Adults (≥ 18 years) with MASLD and documented smoking history were included. A smoking cessation attempt was defined by cessation counseling and/or cessation pharmacotherapy; comparators had no documented cessation attempt. Patients with depressive disorders and competing liver etiologies were excluded. Cohorts were matched 1:1 using propensity scores, and outcomes were analyzed using Cox proportional hazards models. Sensitivity analyses were performed at fixed follow-up horizons of 6 months, 1 year, and 2 years. RESULTS:Among 418,784 eligible patients, 85,639 had a documented cessation attempt and 333,145 did not; after matching, 83,315 patients remained in each cohort. In the matched cohort, cessation attempt was associated with lower hazards of cirrhosis progression (1.7% vs. 2.1%; HR 0.87, 95% CI 0.81-0.93), hepatocellular carcinoma (0.2% vs. 0.3%; HR 0.58, 95% CI 0.48-0.70), portal hypertension (0.8% vs. 1.1%; HR 0.77, 95% CI 0.70-0.86), and MASH progression (2.2% vs. 2.9%; HR 0.76, 95% CI 0.71-0.81). The cessation attempt was also associated with higher hazards of MACE (13.6% vs. 11.4%; HR 1.24, 95% CI 1.20-1.28), peripheral artery disease (4.1% vs. 3.2%; HR 1.33, 95% CI 1.26-1.40), and all-cause mortality (8.5% vs. 7.3%; HR 1.23, 95% CI 1.18-1.27). Fixed-horizon analyses showed similar patterns over time. CONCLUSIONS:In adults with MASLD and smoking history, documented smoking cessation attempts were associated with lower hazards of several liver outcomes but higher cardiovascular event rates and mortality, findings likely influenced by residual confounding and clinical risk clustering in patients receiving cessation interventions.
Background Esophageal variceal bleeding (EVB) is a serious complication of cirrhosis and a major cause of upper gastrointestinal hemorrhage, carrying substantial risks of mortality and treatment failure. Prognostic scores are essential for guiding management. This study evaluated and compared the predictive accuracy of the ABC and MAP(ASH) scores with established models in cirrhotic patients with EVB. Methods We retrospectively analyzed 278 cirrhotic patients admitted for EVB at Da Nang Hospital, Vietnam, between January 2022 and January 2025 who underwent endoscopic variceal ligation. Data were collected for ABC, MAP(ASH), AIMS65, and Glasgow-Blatchford scores. Primary outcomes were in-hospital mortality and 5-day treatment failure. Predictive performance was assessed using AUROCs and statistical comparisons. Results The ABC score achieved the highest AUROC for predicting in-hospital mortality (0.88), significantly surpassing the MAP(ASH), GBS, and AIMS65 scores (p < 0.001 for all pairwise comparisons). A similar trend was observed for predicting 5-day treatment failure, where the ABC score again demonstrated the highest AUROC (0.79), outperforming both the GBS and AIMS65 scores; however, it showed comparable performance to MAP(ASH) (p = 0.19). In addition, the ABC score's risk stratification (low, medium, and high) accurately differentiated patients with varying mortality and treatment failure rates. Conclusion The ABC score is a highly effective and reliable tool for predicting in-hospital mortality and early treatment failure in cirrhotic patients with EVB. While the MAP(ASH) score remains valuable for predicting early treatment failure, the ABC score offers superior overall prognostic accuracy. These findings suggest that the ABC score can guide clinical decisions, particularly in resource-limited settings.
BACKGROUND & AIMS:Prophylactic use of antibiotics was found to decrease mortality in patients with cirrhosis and acute variceal bleeding (AVB). Patients with Child A cirrhosis have a low risk of treatment failure and mortality. The present study was designed to investigate the association between antibiotics and Child-Pugh A patients with AVB. METHODS:This retrospective analysis was conducted on Child-Pugh class A cirrhotic patients presenting with AVB at West China Hospital between January 2016 and November 2022. The outcome indicators evaluated in this study include the rate of treatment failure within five days, mortality within 6 weeks, incidence of nosocomial infections, and 1-year cumulative mortality. RESULTS:This study ultimately enrolled 237 patients. The day of patients' admission was defined as Day 0. A total of 117 patients received prophylactic use of antibiotics on Days 0-1 (Group A), and 120 patients did not receive antibiotics on Days 0-1 (Group B). Baseline characteristics were well-balanced between the two groups. The 5-day treatment failure was 8.5% in Group A and 6.7% in Group B (p = 0.63). The 6-week mortality was 1.71% in Group A and 0% in Group B (p = 0.24). The incidence of nosocomial infection (5.98% vs. 6.67%, p = 1.00) and 1-year cumulative mortality (4.81% vs. 1.89%, p = 0.40) was comparable between the two groups. CONCLUSIONS:The antibiotics' prophylactic use was not associated with 5-day treatment failure or 6-week mortality. Prophylactic use of antibiotics may not be routinely necessary in patients with Child A cirrhosis and AVB.
BACKGROUND:Hepatocellular carcinoma (HCC) is a malignant tumor worldwide with a high mortality rate and recurrence rate. Numerous miRNAs are being applied to the healing and prognosis of HCC. A prior investigation predicted that miR-5003-3p was linked to HCC, but the relevant molecular mechanisms were not clear. AIM:To discover the prognostic value and molecular mechanisms concerned of miR-5003-3p in HCC. METHODS:A total of 125 tumor specimens from HCC patients were obtained in this study, along with corresponding adjacent noncancerous tissue samples collected as a control. The levels of miR-500-3p and MAL2 in tumor tissues and cells were detected by RT-qPCR. The prognostic value of miR-500-3p was evaluated using Kaplan-Meier curve and COX regression model. The effects of miR-500-3p on cellular malignant phenotypes were assessed via CCK-8 and Transwell assays. The target sites of miR-500-3p were identified using bioinformatics analysis. The dual-luciferase reporter assay validated the target relationship between them. RESULTS:miR-5003-3p levels were remarkably elevated in HCC tissues, and late TNM stage (I + II) was dramatically higher versus early TNM stage (III + IV). Lymph node metastasis, TNM stage, and differentiated degree were linked notably to miR-5003-3p expression. Upregulated miR-5003-3p was an independent risk factor for HCC. In vitro, downregulated miR-5003-3p could induce apoptosis and restrain proliferation, migration, and invasion, which could be rescued by depressed MAL2. CONCLUSION:miR-5003-3p may be an independent prognostic factor for HCC. Mechanistically, miR-5003-3p negatively regulates MAL2 to promote cellular processes. These findings highlight the potential of miR-5003-3p as a novel prognostic biomarker and a promising therapeutic target for HCC.
BACKGROUND:Delayed bleeding is a serious complication of endoscopic papillectomy (EP). The aim of this study was to evaluate the efficacy of preventing delayed bleeding of clip after EP. METHODS:Consecutive patients diagnosed with ampullary benign tumors who received EP from January 1st 2013 to December 31st 2024 were analyzed retrospectively. EP was performed with the snare polypectomy technique. Biliary duct stent and pancreatic duct stent were routinely placed. The resection site is closed completely by clips. RESULTS:Fifty major papilla benign tumors patients with a mean age of 55.9 ± 10.7 years were found. All of the lesions were En bloc removed in a single endoscopic procedure. The pancreatic duct stents and biliary duct stents were successfully placed in 47 (94%) and 49 patients (98%), respectively. Two patients had positive horizontal margin, 35 patients had negative horizontal margin, and in 13 patients, horizontal margin was compromised by cautery effect. None of the patients had vertical positive margin, 39 patients had vertical negative margin, and in 11 patients, vertical margin was compromised by cautery effect. Post-EP bleeding was observed in 2 patients (4%), which was classified as mild. Post-EP hyperamylasemia was observed in 13 patients (26%), and post-EP pancreatitis was observed in 7 patients (14%), 6 were mild pancreatitis and 1 was severe pancreatitis. Intraoperative perforation occurred in 1 patient, which was clamped with hemostatic clips. No cholangitis was observed. The mean follow-up duration was 378.1 ± 305.7 days. Histologically confirmed recurrence at the resection site was detected in 6 patients (12%). CONCLUSIONS:This study demonstrated that preventive closure of the resection site by clips was technically feasible and effective in preventing delayed bleeding after EP, without increasing the risk of postprocedure pancreatitis and cholangitis.
BACKGROUND:Spontaneous portosystemic shunts (SPSSs) frequently develop in individuals with cirrhosis. However, their clinical impact on the hepatic venous pressure gradient (HVPG) and liver function remains complex and a subject of ongoing debate. This retrospective study evaluated the relationship between SPSS diameter, particularly ultra-large SPSS, and HVPG, liver dysfunction, and their predictive value in patients with cirrhosis. METHODS:A retrospective study was conducted on 90 cirrhotic patients. The patients were categorized into three groups: no SPSS (none or φ < 3 mm), small SPSS (3 ≤ φ < 8 mm), and large SPSS (φ ≥ 8 mm). The large SPSS group was further stratified into large (8 ≤ φ < 14.5 mm) and ultra-large (φ ≥ 14.5 mm) subgroups based on a receiver operating characteristic (ROC)-derived cutoff for hepatic encephalopathy (HE). Clinical parameters, HVPG, and vascular diameters were analyzed. RESULTS:The large SPSS group had higher total bilirubin and a higher incidence of HE than the no SPSS group. Within the large SPSS cohort, the ultra-large subgroup (≥ 14.5 mm) demonstrated significantly worse liver function (lower albumin, higher bilirubin, prolonged PT, increased INR, and poorer Child-Pugh/MELD scores), a higher proportion of Child-Pugh Class C, and elevated HVPG values (18.7 vs. 16.6 mmHg, p = 0.03) compared to the large subgroup. Critically, SPSS diameter showed a significant positive correlation with HVPG (R = 0.314, p = 0.013). The incidence of HE was also significantly higher in the ultra-large subgroup (55.52% vs. 11%, p = 0.001). CONCLUSIONS:The portal pressure-lowering effect of SPSS does not correlate linearly with its diameter, exhibiting a threshold-dependent attenuation as shunt size exceeds 14.5 mm. This cutoff may serve as a predictor of increased risk for HE and liver dysfunction in cirrhosis, supporting its potential role in clinical risk stratification and decision-making for cirrhosis patients with SPSS.
This study is aimed at evaluating the incidence and clinical characteristics of spontaneous portosystemic shunts (SPSSs) in cirrhotic patients with oesophageal and gastric variceal bleeding (EGVB) and investigating the impact of SPSSs on the course of EGVB. A retrospective analysis of 1110 cirrhotic patients with EGVB was conducted to determine SPSS incidence and characteristics and evaluate the impact of SPSS size and endoscopic treatments. The SPSS incidence was 94.26% (411/436), with gastric renal shunts (78.89%) being the most common. SPSSs were categorized by diameter as follows: S-SPSS (≤ 5 mm), M-SPSS (5-8 mm), and L-SPSS (≥ 8 mm). A larger SPSS diameter was correlated with higher model for end-stage liver disease (MELD) scores, international normalized ratios (INRs), total bilirubin (TB) levels, and portal vein thrombosis. During the 12-month follow-up, the L-SPSS group had a lower rebleeding rate (3.38%) than the S-SPSS (14.64%) and M-SPSS (16.88%) groups. A larger SPSS diameter was associated with a 77% reduction in rebleeding risk (HR = 0.23, p = 0.016). In summary, a larger SPSS diameter is linked to worse liver function but reduced rebleeding risk in cirrhotic patients with EGVB.
BACKGROUND:Healthcare expenditures across the clinical trajectory of hepatitis B virus (HBV) infection are inadequately characterized, particularly among immigrants. Our aim is to quantify HBV-attributable short- and long-term costs among a population of newcomers to the province of Ontario. METHODS:We performed a cost-of-illness study with an incidence-based, matched cohort design, employing linked population-based laboratory and health administrative data, and permanent residence data from Immigration, Refugees and Citizenship Canada (IRCC). We identified newcomers diagnosed with HBV between January 1, 2004, and December 31, 2018, and dichotomized the study cohort into individuals with or without liver complications before diagnosis. We used propensity score matching and phase-of-care costing to quantify monthly attributable costs for each of six HBV phases and longitudinal costs for one, five, and ten years following diagnosis. Costs were quantified in 2021 Canadian dollars. RESULTS:Among n = 30,677 newcomers with HBV, 2.7 percent had complications before diagnosis. Mean monthly phase costs were higher for individuals with complications before diagnosis relative to those without for prediagnosis care ($439, 95% CI: $250-$645 vs. $22, 95% CI: $12-$34), initial care for HBV ($1545, 95% CI: $1196-$1945 vs. $331, 95% CI: $299-$369), continuing care for HBV ($537, 95% CI: $314-$760 vs. $73, 95% CI: $55-$92), and final care ($7271, 95% CI: $3749-$10,747 vs. $3430, 95% CI: $1813-$5061). CONCLUSIONS:Findings emphasize the dynamic nature of HBV-attributable costs and highlight the importance of care following diagnosis and complication onset.
BACKGROUND:Nausea is a distressing symptom affecting ∼7% of the population. Pharmacologic options are limited and often ineffective for chronic nausea. Nonpharmacologic strategies, such as breathing exercises, have shown promise in reducing stress and GI symptoms, but their role in chronic nausea has not been studied. This study addresses this knowledge gap by comparing written diaphragmatic breathing (DB) instructions with a biofeedback device (CalmiGo) for their effect on nausea severity. METHODS:In a prospective study, we investigated the effects of breathing exercises using either written instructions for DB or a biofeedback respiratory practice device (CalmiGo) on self-reported severity of nausea. Participants were randomized to either intervention and asked to practice the exercises three times daily for 3 min each time for 6 Weeks. Nausea was evaluated at baseline and every week for 7 Weeks via online self-reported surveys. RESULTS:A total of 85 adults with nausea (n = 44, 51.7% severe nausea) were randomized to either DB (n = 36) or CalmiGo (n = 49). There was no difference between the two groups at baseline in demographic features, anxiety, depression, or nausea severity. Nausea improved at all-time points in both groups with a medium to large effect size. However, after applying false discovery rate correction, the improvement remained significant for DB only at weeks one to three and borderline significant at weeks four to five and Week 7. There was no difference in response rates between the two groups. Age, body mass index, baseline anxiety, and whether one was diabetic were predictive of improvement in nausea after 4 Weeks. CONCLUSION:In a pilot study, we observed that brief breathing exercises improve nausea. Breathing exercises may be useful as a nonpharmacologic option in the management of nausea, although larger trials are needed to confirm these findings.
BackgroundThis study aimed to investigate the potential causal relationship between inflammatory bowel disease (IBD) and venous leg ulcers (VLU) using Mendelian randomization (MR).Materials and MethodsIndependent genetic variants for IBD and VLU were selected as instruments from previously published genome-wide association studies (GWAS) in people of primarily European descent. MR analyses were carried out utilizing inverse-variance weighted (IVW), weighted median, MR Egger, simple mode, and weighted mode.ResultsGenetically predicted IBD was not associated with VLU, according to the IVW analysis (OR 0.95, 95% CI 0.88-1.03, p = 0.23). MR Egger (OR 0.93, 95% CI 0.76-1.12, p = 0.44), weighted mode (OR 1.06, 95% CI 0.87-1.29, p = 0.55), simple mode (OR 1.03, 95% CI 0.79-1.34, p = 0.83), and weighted median (OR 0.99, 95% CI 0.89-1.10, p = 0.90) all produced results in line with IVW. According to the IVW technique, UC (OR 1.02, 95% CI 0.95-1.10, p = 0.62) and CD (OR 0.97, 95% CI 0.90-1.04, p = 0.36) did not appear to be associated with VLU in subtype analyses.ConclusionThe MR investigation found no genetic evidence to support a causal relationship between IBD and VLU. This finding clarifies that observed clinical associations are unlikely to be driven by shared genetics, and this genetic insight helps refine the clinical assessment of VLU in patients with IBD.
Objective:To preliminarily explore the feasibility and clinical implications of using gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) for assessing the gallbladder ejection fraction (GBEF) in patients with cholecystolithiasis. Methods:This retrospective analysis encompassed 81 patients with gallstones who underwent Gd-EOB-DTPA-enhanced MRI. Gallbladder volume was measured during fasting and at 1 h after a lipid-rich meal to calculate the GBEF. Two radiologists independently reviewed the images for GBEF, structural anomalies, and biliary patency. Results:The mean GBEF was 62.29% ± 25.2%. Sixty patients demonstrated a GBEF > 50%, while 21 had a GBEF ≤ 50%. The imaging also facilitated the identification of gallbladder malformations (41/81) and abnormal pancreaticobiliary junctions (20/81). Bile flow into the gallbladder via the cystic duct and into the duodenum was observed in 66 patients. Conclusion:This exploratory study suggests that Gd-EOB-DTPA-enhanced MRI is a feasible modality for simultaneous anatomical evaluation and functional assessment of the GBEF in cholecystolithiasis patients. It provides a comprehensive visualization of biliary dynamics. However, the findings are preliminary, and further validation against standard modalities with controlled study design is required to establish its accuracy and clinical utility.
Purpose:Inflammation is implicated in the pathogenesis of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs); however, the causal nature of this association remains unclear. This study sought to evaluate the causal relationships between GEP-NENs and inflammatory factors using a two-sample Mendelian randomization (MR) approach. Methods:We performed a two-sample MR analysis to investigate the causal associations between 91 inflammatory proteins and 731 immune cell traits as exposures and the five subtypes of GEP-NENs as the outcomes. The analytical approach employed various methodologies, such as inverse variance weighting, MR-Egger, weighted mode, weighted median, and simple mode. To evaluate the robustness of the results, sensitivity analyses were conducted, which encompassed MR Egger regression, MR multiple gene residual and outlier detection, leave-one-out analysis, and Cochran's Q test. False discovery rate (FDR) correction was applied, and causal relationships at the gene level were deemed significant at p < 0.05 after FDR adjustment. Results:After FDR correction, the findings revealed robust causal associations between genetically predicted HLA DR++ monocyte %leukocyte (OR = 3.09, 95% CI: 1.76-5.44, p < 0.001, FDR = 0.022), HLA DR on CD14+ CD16- monocyte (OR = 1.72, 95% CI: 1.34-2.22, p < 0.001, FDR = 0.010), and HLA DR on CD14+ monocyte (OR = 1.76, 95% CI: 1.36-2.29, p < 0.001, FDR = 0.010) and genetically predicted stomach NENs. Reverse analysis revealed that GEP-NENs had no major impact on inflammation. Conclusion:These findings reveal the immune mechanisms underlying GEP-NENs and highlight potential therapeutic strategies targeting the immune microenvironment of GEP-NENs.
Background and Aims:Acute upper gastrointestinal (UGI) bleeding from variceal and nonvariceal sources is a leading cause of morbidity and mortality. Although current international guidelines recommend performing endoscopy within 24 h of presentation, the added value of very early ("urgent," < 6 h) versus "early" (6-24 h) endoscopy remains unclear. Therefore, this study aimed to analyze the impact of urgent versus early endoscopy on clinical outcomes. Methods:In this retrospective cohort study, we reviewed the medical records of 599 patients admitted to the emergency or gastroenterology department who underwent UGI endoscopy. Patients were stratified by timing, urgent endoscopy within 6 h of specialist consultation and early endoscopy between 6-24 h postconsultation. The protocol was approved by the University of Rzeszów Ethics Committee and conducted in accordance with the Declaration of Helsinki. Results:Compared to the early group, patients undergoing urgent endoscopy were younger (p = 0.013), predominantly male, and had higher baseline heart rates (p = 0.0371). Apart from more frequent hypertension in the early group (p = 0.0007), comorbiditiy profiles were otherwise similar. The urgent endoscopy group had longer hospital stays (6.88 vs. 5.95, p = 0.774), more frequent rebleeding within 7 days (p = 0.0213), and slightly higher 30-day all-cause mortality rates. Factors associated with poor prognosis included increases in Rockall's and GB's scores (42% and 19% higher risk per point, respectively) and the presence of active bleeding (105% higher odds). Conclusions:In unadjusted analyses, urgent endoscopy (< 6 h) was associated with worse outcomes, likely reflecting the selection of more severely ill patients. After propensity-score matching for baseline risk factors, however, the timing of endoscopy (< 6 h vs. 6-24 h) was no longer an independent predictor of outcomes. These findings suggest that clinicians' decisions and outcome differences are driven by overall severity of presentation and comorbid burden, rather than the effect of ultra-early endoscopy itself.
Introduction:Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease and a leading cause of food impaction in pediatric populations, with potential functional and structural complications. Proton-pump inhibitors (PPIs) are widely used as first-line therapy, but the response rate in Colombian children remains unknown. This study aimed to determine the initial histologic response to PPI therapy and describe clinical, endoscopic, and histological characteristics in a sample of pediatric patients with EoE from Bogotá, Colombia. Methodology:A retrospective observational longitudinal study of patients aged 2-18 years diagnosed with EoE at a tertiary care center between 2015 and 2022 was conducted. Patients underwent initial clinical and endoscopic assessment confirming esophageal eosinophilia (≥ 15 eosinophils per high-power field [eos/hpf]), followed by at least 8-week course of PPI therapy and a subsequent clinical-endoscopic re-evaluation. Treatment response was defined histologically as < 15 eos/hpf in follow-up esophageal biopsy. Demographic, clinical, endoscopic, and histological data were analyzed using descriptive and bivariate statistics. Results:We included 34 patients (median age 11 years; 61.8% boys). Sixteen (47%) achieved histological remission with initial PPI therapy. Being esomeprazole preferred in 88%, with median dose 1.37 mg/kg/day. No significant differences were observed between responders and nonresponders in demographic variables, familial and personal atopic history, symptoms, or endoscopic findings. Histologically, responders demonstrated significant reductions in eosinophil counts, as well as improvements in basal zone hyperplasia, eosinophilic abscesses, and eosinophil surface layering (all p < 0.005). Discussion:This is the first study to assess PPI response in Colombian pediatric EoE patients, demonstrating a response rate consistent with existing literature. Histologic evaluation was identified as the most reliable marker of treatment success, underscoring the critical role of histopathological follow-up in this disease.
Background:Due to poverty and the pervasive thin-body ideal, undernutrition poses a significant challenge in both developed and economically undeveloped nations. Maternal nutritional deprivation has been linked to negative outcomes for the health of the fetus, a higher chance of metabolic syndrome, and adult obesity. Aim:Considering the functions of the liver, this study aims to assess the interface between maternal malnutrition and morphological changes of the liver in the first and second generations of aged offspring. Methods:This experimental study conducted in the Department of Anatomy, Histology, and Anthropology involved 26 rats divided into 3 groups: a control group fed a standard diet, a group subjected to 50% dietary restriction before pregnancy, and a group experiencing 50% dietary restriction before and during pregnancy. Histopathological examination was conducted on the livers of both first- and second-generation rat offspring to assess the occurrence of hepatic steatosis, ballooning, inflammation, and fibrosis. Data comparisons were performed using the Kruskal-Wallis test. Results:Both the first- and second-generation experimental groups displayed a more pronounced steatosis and ballooning index compared to the control group. In addition to this, both male and female progeny of the experimental groups exhibited higher levels of steatosis and ballooning. Offspring of mothers undernourished before pregnancy demonstrated a more severe case of steatosis, whereas offspring from mothers fed a low-calorie diet before and throughout pregnancy showed a higher ballooning index. In the second generation, these changes were less profound than those seen in the first generation. Notably, both experimental groups of the first generation exhibited significantly higher levels of steatosis compared to their equivalent second-generation counterparts. Conclusions:According to this study, there is a link between maternal undernutrition and a higher risk of nonalcoholic steatohepatitis or nonalcoholic fatty liver disease in the offspring's later life.
Objective:Except for liver transplantation, no definitive treatment exists for hepatocellular carcinoma (HCC) in individuals suffering from decompensated liver cirrhosis. This research evaluated the feasibility and outcomes of microwave ablation (MWA) treatment in this patient population. Methods:This research involved individuals diagnosed with HCC and decompensated cirrhosis who underwent MWA between 2019 and 2022. The analysis examined complications associated with the procedure, the effectiveness of treatment, patient survival rates, and the variations in blood test results and liver function reserves before and after MWA. Results:The 62 enrolled patients were predominantly male (n = 48), and the average age was 59.06 years. Fifty-one patients were diagnosed with HBV-related cirrhosis. The tumor characteristics varied: 47 patients had single lesions with diameters ranging from 8 to 57 mm. Following the MWA procedure, there was a notable rise in the levels of alanine transaminase, aspartate transaminase, total bilirubin, prothrombin time, and the Child-Pugh, albumin-bilirubin, and model for end-stage liver disease scores (p < 0.05). Analysis of survival data indicated that tumor diameter < 3 cm, complete response (CR), meeting the Milan criteria, and Barcelona Clinic Liver Cancer (BCLC) Stage 0-A were linked to a more favorable prognosis. Multivariable Cox regression analysis identified achieving a CR as the strongest independent predictor for improved overall survival (HR = 0.25, 95% CI [0.09, 0.66], p = 0.005). Furthermore, the Milan criteria were independently associated with reduced risk of tumor progression in both univariate and multivariate analyses. Conclusion:MWA is a safe procedure for individuals with HCC and decompensated liver cirrhosis. CR is associated with a better prognosis.
