BACKGROUND: The causal relationship between type 2 diabetes mellitus (T2DM) and the various liver disease phenotypes remains uncertain. RESEARCH DESIGN AND METHODS: Our study provides a comprehensive causal atlas by asse...BACKGROUND: The causal relationship between type 2 diabetes mellitus (T2DM) and the various liver disease phenotypes remains uncertain. RESEARCH DESIGN AND METHODS: Our study provides a comprehensive causal atlas by assessing the causal roles of T2DM across 12 major liver conditions using summary data from genome-wide association studies. RESULTS: Our study indicated significant genetic correlations between T2DM and five types of liver diseases, with suggestive levels for three additional types. Furthermore, we found evidence of the causal effects of T2DM on seven types of liver diseases. Specifically, T2DM showed significant causality with metabolic dysfunction-associated steatotic liver disease [odds ratio (OR) = 1.49, 95% confidence interval (CI): 1.37-1.62, P = 2.55 × 10-21], cirrhosis of liver (OR = 1.18, 95% CI: 1.05-1.33, P = 3.98 × 10-3), chronic hepatitis (OR = 1.20, 95% CI: 1.06-1.37, P = 3.72 × 10-3), and hepatocellular carcinoma (OR = 1.31, 95% CI: 1.10-1.56, P = 3.02 × 10-3). In addition, suggestive causality was found between T2DM and nonalcoholic steatohepatitis (OR = 1.45, 95% CI: 1.08-1.95, P = 0.012), fibrosis of liver (OR = 1.47, 95% CI: 1.08-2.00, P = 0.015), and malignant liver neoplasm (OR = 1.21, 95% CI: 1.04-1.42, P = 0.013). CONCLUSION: Our research has comprehensively revealed the clear causal relationship between T2DM and specific liver diseases, emphasizing the importance of preventing such diseases in patients with T2DM. These findings not only confirm and expand the existing knowledge framework regarding the relationship between T2DM and liver diseases but also provide new insights for clinical practice and future research directions.
OBJECTIVE: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, with a poor prognosis due to late diagnosis and limited treatment options. The secretome, encompassing proteins, metabolites, and...OBJECTIVE: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, with a poor prognosis due to late diagnosis and limited treatment options. The secretome, encompassing proteins, metabolites, and extracellular vesicles secreted by cells, has emerged as a promising tool for early detection, risk stratification, and therapeutic targeting in HCC. Recent studies suggest that secretome-derived biomarkers improve diagnostic accuracy and predict survival outcomes. However, variability in methodologies and findings necessitates a comprehensive synthesis of evidence. METHODS: A systematic review and meta-analysis were conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, EMBASE, and Scopus databases were searched on 2 May 2025 for studies evaluating the diagnostic and prognostic value of the secretome in HCC. Eligibility criteria included original research reporting sensitivity, specificity, or survival outcomes. Risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies-2. Pooled estimates of sensitivity, specificity, and hazard ratios (HRs) were calculated using random-effects models, with heterogeneity assessed via I² statistics. RESULTS: Five studies met the inclusion criteria. The secretome demonstrated high diagnostic accuracy, with a pooled sensitivity of 95.9% [95% confidence intervals (CI): 40-100] and specificity of 89.6% (95% CI: 43.1-99). Moderate heterogeneity (I² = 44%) was observed. For survival outcomes, the pooled HR was 2.37 (95% CI: 0.87-6.41), though statistical significance was not reached (P = 0.07). CONCLUSIONS: The secretome shows promise as a diagnostic and prognostic tool in HCC, with high sensitivity and specificity. However, further large-scale, standardized studies are needed to validate these findings and facilitate clinical translation.
OBJECTIVES: About 30% of the patients with inflammatory bowel disease (IBD) develop malignancies, which constitute the second cause of death, after cardiovascular diseases. This study aimed to investigate the prevalence,...OBJECTIVES: About 30% of the patients with inflammatory bowel disease (IBD) develop malignancies, which constitute the second cause of death, after cardiovascular diseases. This study aimed to investigate the prevalence, risk factors, and outcome of malignancies in IBD patients in Crete. METHODS: This is a retrospective study of prospective longitudinal IBD registries at the University Hospital and Venizelion General Hospital of Heraklion, Crete. IBD patients with malignancies were compared with IBD controls without malignancies [matching 1:3 according to sex, IBD diagnosis (ulcerative colitis, Crohn's disease; CD), age (±5 years)]. RESULTS: From 2.382 IBD patients, 107 (4.5%) were diagnosed with cancer during their follow-up. Among those, 49 (45.8%) were females, and 54 (50.5%) had CD. The majority were extraintestinal malignancies, while 12 (11.2%) had colorectal cancer. In the multivariate analysis, inflammatory CD phenotype (Odds ratio (OR), 0.28; 95% confidence interval (CI), 0.09-0.58) was protective, whereas colonic location (OR, 4.8; 95% CI, 1.81-12.79) remained a risk factor for malignancy. Twelve (11.2%) had a cancer recurrence, 19 (17.8%) died of cancer, whereas the initiation of biologics, immunomodulators (IMMs) or in combination after the cancer diagnosis did not have a negative impact either on the survival or on the possibility of recurrence. CONCLUSION: The rate of malignancy in IBD patients in Crete is 4.5%. CD disease location and behavior are associated with the development of malignancies. No association with biologics and/or IMMs previous exposure was found. Moreover, initiation of biologics or IMMs after cancer diagnosis was not associated with an adverse impact either on survival or on cancer recurrence.
Pavoni M, Tartagni M, Correale R
… +13 more, Gatta L, Fiorini G, Racca D, Zullo A, Arlotti L, Massarenti G, Rosa B, Marchesani C, Collatuzzo G, Manta R, Imbrogno A, Borghi C, Vaira D
Eur J Gastroenterol Hepatol
· 2026 Mar · PMID 41757610
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BACKGROUND: Helicobacter pylori (H. pylori) is one of the most common bacterial infections, and it causes chronic gastritis, peptic ulcers, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer. H. pylor...BACKGROUND: Helicobacter pylori (H. pylori) is one of the most common bacterial infections, and it causes chronic gastritis, peptic ulcers, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer. H. pylori infection can be essentially detected by invasive [i.e. requiring an upper gastrointestinal endoscopy (UGE)], and noninvasive techniques. The principle of the urea breath test exploits the abundant quantities of urease produced by H. pylori. Recently, advances in the field of micro-electromechanical systems and nano-electromechanical systems have been proposed. This study aimed to evaluate the accuracy of this new miniaturized column-free portable gas-mass spectrometry (GMS) test compared with the standard GMS to diagnose H. pylori infection before and after eradication therapy. METHODS: Consecutive patients never treated for H. pylori infection and referred to our unit to perform a UGE between April and November 2024 were evaluated for this blind prospective trial. Patients' samples were analysed with both methods and data were compared. RESULTS: A total of 28 patients were enrolled and 92 were H. pylori positive. The data obtained from the two tests were compared, and no statistically significant difference was observed. DISCUSSION: Our experience highlights the potential for introducing new diagnostic tools that are less demanding in terms of cost and labour, without compromising diagnostic accuracy. To our knowledge, this is the first time that an innovative diagnostic tool proves to be as compact and as reliable; for this reason, it deserves to be implemented in clinical practice.
OBJECTIVE: Programmed cell death protein 1 and programmed death-ligand 1 (PD-L1) inhibitors are increasingly implicated in cases of drug-induced liver injury (DILI). While previous studies have established a correlation...OBJECTIVE: Programmed cell death protein 1 and programmed death-ligand 1 (PD-L1) inhibitors are increasingly implicated in cases of drug-induced liver injury (DILI). While previous studies have established a correlation between chronic liver diseases and DILI, investigations into the association between steatotic liver disease (SLD) and DILI remain limited. This study aimed to evaluate the clinical characteristics and risk factors associated with PD-(L)1 inhibitor-related DILI, with particular emphasis on the impact of SLD on DILI incidence. METHODS: Clinical data from patients with extrahepatic malignancies who received PD-(L)1 inhibitors between January 2020 and December 2024 were retrospectively analysed. Causality between liver injury events and PD-(L)1 inhibitors was assessed using the updated Roussel Uclaf Causality Assessment Method. RESULTS: Among the 958 patients treated with PD-(L)1 inhibitors, 62 (6.5%) developed PD-(L)1 inhibitor-related DILI. A total of 364 (38.0%) had SLD, of whom 310 (32.4%) were classified as metabolic dysfunction-associated steatotic liver disease (MASLD), 18 (1.9%) as MASLD with increased alcohol consumption, and 36 (3.8%) as MASLD with chronic hepatitis virus infection. Multivariate analysis demonstrated that patients with SLD had a 5.6-fold increased risk of developing DILI (95% confidence interval: 3.42-9.12, P < 0.001); however, no association was observed between MASLD and an increased DILI risk. Notably, DILI risk was significantly higher in patients with steatosis combined with chronic hepatitis virus infection or heavy alcohol consumption. CONCLUSION: Hepatic steatosis is associated with an increased risk of PD-(L)1 inhibitor-related liver injury in patients with extrahepatic malignancies, particularly in the presence of multiple underlying aetiologies.
Alcoholic hepatitis is a form of acute liver injury with significant morbidity and mortality. Several scoring systems have been developed and used to predict mortality, including Maddrey's discriminant function (MDF), mo...Alcoholic hepatitis is a form of acute liver injury with significant morbidity and mortality. Several scoring systems have been developed and used to predict mortality, including Maddrey's discriminant function (MDF), model for end-stage liver disease (MELD), and modified MELD including sodium (MELD-Na). We conducted a systematic review of Pubmed, Embase, and Cochrane Library to compare the accuracy of these scores in alcoholic hepatitis mortality prediction. The pooled sensitivity and specificity of MDF for mortality prediction in 28 days were 0.898 [95% confidence interval (CI) 0.777-0.957, I2 = 0%] and 0.370 (95% CI: 0.271-0.482, I2 = 78%), respectively; in 90 days, they were 0.898 (95% CI: 0.799-0.951, I2 =21%) and 0.346 (95% CI: 0.246-0.463, I2 = 88%), respectively. The pooled sensitivity and specificity of MELD for mortality prediction in 28 days were 0.862 (95% CI: 0.755-0.926, I2 = 0%) and 0.697 (95% CI: 0.552-0.812, I2 = 82%), respectively; in 90 days, they were 0.884 (95% CI: 0.802-0.935, I2 = 21%) and 0.557 (95% CI: 0.300-0.787, I2 = 96%), respectively. The pooled sensitivity and specificity of MELD-Na for mortality prediction in 28 days were 0.652 (95% CI: 0.429-0.823, I2 = 79%) and 0.757 (95% CI: 0.666-0.830, I2 = 91%), respectively; in 90 days, they were 0.701 (95% CI: 0.661-0.737, I2 = 53%) and 0.816 (95% CI: 0.711-0.888, I2 = 94%), respectively. No significant statistical difference was observed when comparing area under the curve of these scores.
PURPOSE: This study compared the incidence of adverse events in patients with unresectable intrahepatic cholangiocarcinoma (ICC) receiving drug-eluting bead transarterial chemoembolization (DEB-TACE) either alone or in c...PURPOSE: This study compared the incidence of adverse events in patients with unresectable intrahepatic cholangiocarcinoma (ICC) receiving drug-eluting bead transarterial chemoembolization (DEB-TACE) either alone or in combination with immune checkpoint inhibitors (ICIs). METHODS: A retrospective analysis was conducted on patients with unresectable ICC who received either DEB-TACE alone or in combination with ICIs treatment from February 2019 to April 2024. Of the enrolled 247 ICC patients, 178 received DEB-TACE combined with ICIs treatment, while 69 patients received DEB-TACE alone. Adverse events were recorded and compared between the two groups. Binary logistic regression analysis was used to determine the significant risk factors of adverse events. RESULTS: The overall incidence of adverse events was 19.1% (34/178) in the DEB-TACE+ICIs group and 13.0% (9/69) in the DEB-TACE group. The DEB-TACE+ICIs group exhibited a statistically significantly higher incidence of liver abscesses than the DEB-TACE group (13.5% vs. 2.9%, P = 0.015). Binary logistic regression analysis showed that combined ICIs treatment ( P = 0.027, odds ratio = 5.583, 95% confidence interval: 1.212-25.725) and grade 1 artery occlusion ( P = 0.001, odds ratio = 31.380, 95% confidence interval: 4.098-240.263) were independently associated with an increased risk of developing liver abscess. CONCLUSION: Combined ICIs treatment and grade 1 arterial occlusion were independently associated with an increased risk of liver abscesses. Clinicians should closely monitor for liver abscess formation when administering DEB-TACE in combination with ICIs, particularly in patients with grade 1 arterial occlusions.
BACKGROUND: Hepatocellular carcinoma (HCC) is a major complication of chronic hepatitis C virus (HCV) infection, and its early diagnosis is limited by the suboptimal performance of α-fetoprotein. Circulating microRNAs (m...BACKGROUND: Hepatocellular carcinoma (HCC) is a major complication of chronic hepatitis C virus (HCV) infection, and its early diagnosis is limited by the suboptimal performance of α-fetoprotein. Circulating microRNAs (miRNAs) have emerged as promising noninvasive biomarkers for detecting malignant transformation in high-risk patients. This study evaluated the diagnostic value of serum miRNA-141.3p, miRNA-155, miRNA-106b, and miRNA-423 in distinguishing HCC from liver cirrhosis among HCV-infected individuals and developed a combined miRNA-based predictive score. METHODS: A total of 145 participants were included: 42 patients with HCV-related HCC, 83 cirrhotic HCV patients without malignancy, and 20 healthy controls. Serum miRNA levels were quantified. Diagnostic performance was assessed by receiver operating characteristic curve analysis, and multivariate discriminant analysis was used to construct a composite index, termed the miR-HCC Detect score. RESULTS: All four miRNAs were significantly upregulated in cirrhosis and HCC compared with healthy controls ( P < 0.05), with the highest expression observed in HCC. Individually, miRNA-155 and miRNA-141.3p demonstrated strong diagnostic accuracy for differentiating HCC from controls [area under the curve (AUC) = 0.988 and 0.924, respectively], while miRNA-106b and miRNA-423 showed moderate discrimination between HCC and cirrhosis. The miR-HCC Detect score achieved an AUC of 0.824, with 96% sensitivity and 62% specificity at a cutoff value of 0.44, and clearly differentiated cirrhosis from HCC (0.63 ± 0.16 vs. 5.1 ± 1.67; P < 0.001). CONCLUSION: These circulating miRNAs represent promising noninvasive biomarkers for HCC detection in HCV-infected patients. The miR-HCC Detect score outperforms individual miRNAs and may improve early HCC surveillance.
Colitis cystica profunda (CCP) is an uncommon, benign colorectal lesion that can mimic malignancy. We conducted a systematic review of histologically confirmed CCP case reports and series to define epidemiology, presenta...Colitis cystica profunda (CCP) is an uncommon, benign colorectal lesion that can mimic malignancy. We conducted a systematic review of histologically confirmed CCP case reports and series to define epidemiology, presentation, diagnostic yield, management, and outcomes. Following PRISMA 2020, Embase, PubMed/MEDLINE, Web of Science, and CINAHL were searched (1965-2025); two reviewers independently screened studies and extracted demographic, clinical, imaging, histologic, treatment, and outcome data. Sixty-five studies (92 patients) met criteria. Mean age was 40 ± 12 years (median 39), and 54% were male. Rectal bleeding (70%), mucus discharge (32%), diarrhea (24%), and abdominal/rectal pain (26%) were most common; 12% were asymptomatic. Lesions were predominantly distal (rectum 61%), and superficial biopsies reached the submucosa in only 32%, contributing to frequent sampling error; Endoscopic ultrasound (EUS) and cross-sectional imaging typically showed submucosal cystic lesions with intact muscularis propria. Conservative and medical therapy were each attempted in 16% of patients, endoscopic resection in 14%, and surgery in 67%, most commonly local transanal/perineal excision (40% of surgeries) or segmental/partial colectomy (32% of surgeries). Dysplasia was reported in 10% and coexisting invasive adenocarcinoma in 4% at diagnosis; no subsequent malignant transformation was reported over a median follow-up of 8.4 months. Post-operative morbidity occurred in 5% and recurrence in 4%. CCP is a rare but important mimic of colorectal cancer; diagnosis is optimized with deep tissue sampling and high-resolution imaging. When feasible, organ-preserving endoscopic or local excision can achieve durable symptom resolution with low morbidity while avoiding unnecessary radical surgery.
Hepatic failure is a potentially fatal complication in hepatocellular carcinoma (HCC) patients undergoing transarterial chemoembolization (TACE). However, there is a lack of clear predictive factors for hepatic failure a...Hepatic failure is a potentially fatal complication in hepatocellular carcinoma (HCC) patients undergoing transarterial chemoembolization (TACE). However, there is a lack of clear predictive factors for hepatic failure after TACE in HCC patients. This study aimed to identify all available data and determine the risk factors associated with hepatic failure after TACE in HCC patients. A systematic review and meta-analysis included 9 studies with a total of 1654 patients. The results showed that factors significantly associated with hepatic failure after TACE included female sex [odds ratio (OR) = 1.38, 95% confidence interval (CI) 1.09-1.75], low albumin [mean difference (MD) = -0.34, 95% CI: -0.61 to -0.07] and platelet (MD = -15.84, 95% CI: -23.62 to -8.05), high total bilirubin (MD = 0.64, 95% CI: 0.24-1.04), aspartate aminotransferase (MD = 25.45, 95% CI: 3.88-47.01), alanine aminotransferase (MD = 8.79, 95% CI: 0.15-17.42), international normalized ratio (MD = 0.18, 95% CI: 0.03-0.32), alpha-fetoprotein (MD = 74.05, 95% CI: 64.12-83.99), Model for End-Stage Liver Disease (MD = 3.41, 95% CI: 0.95-5.87), and high Child-Turcotte-Pugh class (OR = 4.66, 95% CI: 1.52-14.28), larger tumor size (MD = 7.75, 95% CI: 6.87-8.63), presence of portal vein thrombosis (OR = 1.78, 95% CI: 1.19-2.67), and high indocyanine green retention test after 15 min (ICG-R15 test) (MD = 16.75, 95% CI: 13.16-20.34). These findings may help clinicians with treatment planning, patient counseling, and postprocedural monitoring.
Dieulafoy's lesion is a rare but potentially life-threatening cause of gastrointestinal bleeding because of an abnormally dilated submucosal artery that erodes the overlying epithelium without a primary ulceration. Typic...Dieulafoy's lesion is a rare but potentially life-threatening cause of gastrointestinal bleeding because of an abnormally dilated submucosal artery that erodes the overlying epithelium without a primary ulceration. Typically located in the proximal stomach near the esophagogastric junction, Dieulafoy's lesions can also occur throughout the whole gastrointestinal tract, including the oesophagus, small bowel, and colon. Rare cases have been reported in the respiratory tract. Dieulafoy's lesion accounts for approximately 3.5% of gastrointestinal bleeding cases, with mortality rates ranging from 23 to 79%, mainly because of the risk of rebleeding and surgical complications. The aetiology of Dieulafoy's lesion remains unclear, despite congenital vessel dilation and stress-induced factors have been invoked. Common symptoms include haematemesis, melena, and signs of acute arterial bleeding; nevertheless, the diagnosis is often challenging because of intermittent haemorrhage. Endoscopic examination typically reveals a pigmented protuberance without ulceration; however, excessive bleeding or small lesion size may hinder detection. Early endoscopy (within 12 h) significantly improves diagnostic accuracy. Therapeutic approaches may differ in relation to the presentation and lesion location. Endoscopic haemostasis is the preferred technique, achieving success in nearly 90% of cases. Haemostatic procedures include injective, thermal, and mechanical methods. Angiographic embolisation or surgery are limited in cases of endoscopic treatment failure. Advances in endoscopic therapy have reduced Dieulafoy's lesion-related mortality from 80 to 8.6%, despite rebleeding remains a concern. A multidisciplinary approach, combining endoscopy, radiology, and surgery when necessary, is crucial for optimal management, thus improving patient outcomes.
Tanaka Y, Tamaki N, Nakanishi H
… +19 more, Shima T, Taguchi M, Yamazaki Y, Uchihara N, Seike R, Kimura S, Yagita J, Kobayashi R, Kasano Y, Komiyama Y, Takaura K, Takada H, Tanaka S, Maeyashiki C, Yasui Y, Tsuchiya K, Takahashi Y, Izumi N, Kurosaki M
BACKGROUND AND AIM: Lactulose and rifaximin are recommended therapies for hepatic encephalopathy. Although the usefulness of the combination is evident, there is a paucity of real-world data regarding the efficacy of lac...BACKGROUND AND AIM: Lactulose and rifaximin are recommended therapies for hepatic encephalopathy. Although the usefulness of the combination is evident, there is a paucity of real-world data regarding the efficacy of lactulose and rifaximin combination therapy when used immediately after overt hepatic encephalopathy (OHE) onset. This study aimed to clarify the prophylactic effect of using combination therapy as a first-line treatment in real-world clinical practice. METHODS: In this retrospective cohort study, 96 patients who had developed OHE and subsequently improved were included. As first-line prophylactic therapy, 37 patients received lactulose and rifaximin combination therapy, while 59 patients received lactulose monotherapy. The primary outcome was OHE recurrence within 12 months. RESULTS: The cohort represented a real-world Japanese population of elderly patients with advanced cirrhosis. The 12-month cumulative incidence rates of OHE recurrence were significantly lower in the combination therapy group (25.0%) compared with the monotherapy group (49.3%) (Gray's test P = 0.026). In the Fine-Gray multivariable analysis, combination therapy significantly reduced recurrence risk, with a subdistribution hazard ratio of 0.44 (95% confidence interval: 0.20-0.97). CONCLUSION: Lactulose and rifaximin combination therapy significantly suppressed OHE recurrence more effectively than lactulose monotherapy when used as a first-line treatment. Our findings suggest clarify the prophylactic benefit of the two-drug combination; this therapy may be a more useful first-line treatment for patients with OHE and could be recommended.
BACKGROUND: Infliximab's efficacy as a second-line agent in moderate or severe ulcerative colitis after prior advanced therapy failure is unclear. Registration trials for infliximab did not assess its efficacy after expo...BACKGROUND: Infliximab's efficacy as a second-line agent in moderate or severe ulcerative colitis after prior advanced therapy failure is unclear. Registration trials for infliximab did not assess its efficacy after exposure to other advanced therapies, a sequence in which it is increasingly used. We evaluate infliximab's second-line effectiveness, identify predictors of response, and compare outcomes to its first-line use. METHODS: We conducted a retrospective cohort study of adults with ulcerative colitis treated with infliximab at a tertiary care center. Patients were categorized by line of therapy. Clinical and endoscopic outcomes at 1 year were compared between first-line and second-line users. Multivariable logistic regression was used to assess predictors of 1-year clinical remission. RESULTS: Among 225 included patients, 143 received infliximab first-line and 82 as second-line or subsequent therapy. Clinical response at 1 year was significantly lower in second-line users (odds ratio 0.53, 95% confidence interval: 0.28-0.99, P = 0.049) and remained significantly lower after adjustment for biosimilar and concurrent steroid use. Dose escalation was more common with second-line use (57.3% vs. 42.0%, P = 0.026). Endoscopic and histologic remission was numerically lower in second-line users (47.7% vs. 33.3% and 27.0% vs. 41.7%, respectively), though these were not statistically significant ( P = 0.180 and 0.099, respectively). CONCLUSION: Infliximab remains effective as a second-line agent in ulcerative colitis, though with reduced response and higher rates of dose escalation as compared to use first-line. These findings support its continued use while highlighting the need for optimized patient selection and treatment strategies in therapy-exposed populations.
Gastrointestinal angiodysplasia is frequently observed in patients with aortic stenosis and may present with bleeding and anemia. We conducted a systematic review and meta-analysis to estimate its prevalence in this popu...Gastrointestinal angiodysplasia is frequently observed in patients with aortic stenosis and may present with bleeding and anemia. We conducted a systematic review and meta-analysis to estimate its prevalence in this population and to summarize outcomes after valve intervention. Following PRISMA 2020, we searched PubMed, Scopus, and Web of Science and registered the protocol in PROSPERO (CRD42024550839). Eligible observational studies reporting angiodysplasia, von Willebrand factor abnormalities, or both in aortic stenosis were appraised for quality and pooled using a random effects model; heterogeneity and publication bias were assessed with I ² and Egger's test. Eleven studies were included. The pooled prevalence of gastrointestinal angiodysplasia among patients with aortic stenosis was 6.3% (95% confidence interval: 4.51-8.38, I ² = 98.68, P < 0.0001), with no evidence of publication bias. Across studies that reported longitudinal outcomes, aortic valve replacement or transcatheter aortic valve implantation was associated with a reduction in lesion burden and lower rates of gastrointestinal bleeding, anemia, transfusion, and readmission, although early postprocedural bleeding could occur and typically declined over follow-up. These findings indicate that angiodysplasia is a clinically relevant comorbidity in aortic stenosis and support proactive gastrointestinal evaluation in patients with anemia or unexplained bleeding. Standardized diagnostic criteria and prospective studies are needed to clarify long-term outcomes after valve therapy and to define screening and management pathways.
Constipation is a common gastrointestinal disorder with limited effective treatments and a significant impact on quality of life. Plecanatide, a guanylate cyclase-C agonist, has shown promise in improving symptoms with a...Constipation is a common gastrointestinal disorder with limited effective treatments and a significant impact on quality of life. Plecanatide, a guanylate cyclase-C agonist, has shown promise in improving symptoms with a favorable safety profile. This meta-analysis aimed to evaluate the effectiveness and tolerability of plecanatide in patients with irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC). A comprehensive search was performed across Medline, Embase, Cochrane CENTRAL, and ClinicalTrials.gov up till March 2025. Only randomized controlled trials (RCTs) comparing plecanatide with placebo in IBS-C and CIC were included. A random-effects model was used to calculate risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals. Study quality was assessed using the Cochrane risk of bias tool (RoB 2.0) and evidence certainty with the Grading of Recommendations, Assessment, Development, and Evaluation approach. Data from seven RCTs involving 6319 patients (CIC: 3707 and IBS-C: 2612) were pooled. Among these, 4350 patients received plecanatide and 1969 received a placebo. In patients with CIC, plecanatide significantly improved spontaneous bowel movements (SBMs) per week (MD = 1.39), stool consistency (MD = 0.70), SBMs within 24 h (RR = 1.35), complete SBMs within 24 h (RR = 1.88), and overall responders (RR = 1.73). In patients with IBSC, it improved stool consistency (MD = 0.79), SBMs within 24 h (RR = 1.42), and overall responders (RR = 1.64). Diarrhea risk was higher with plecanatide (RR = 4.11), while other adverse events were comparable to placebo. In conclusion, plecanatide significantly improves bowel symptoms in CIC and IBS-C patients. None of the adverse events showed significant treatment differences except diarrhea, which showed a fourfold higher risk in the plecanatide group.