Indications of Helicobacter pylori Eradication Treatment and Its Influence on Prescriptions and Effectiveness (Hp-EuReg).

BACKGROUND: The influence of indications for Helicobacter pylori investigation on prescriptions and effectiveness is unknown. The aim of the study was to assess the impact of indications for H. pylori investigation on prescriptions, effectiveness, compliance, and tolerance. METHODS: International, prospective, non-interventional registry of the management of H. pylori infection by European gastroenterologists (Hp-EuReg). Treatment-näive patients registered from 2013 to 2023 at e-CRF AEG-REDCap were analyzed. The effectiveness was assessed by modified intention-to-treat analysis. RESULTS: Overall, 53,636 treatment-naïve cases from 34 countries were included. Most frequent indications were: dyspepsia with normal endoscopy (49%), non-investigated dyspepsia (20%), duodenal ulcer (11%), gastric ulcer (7.7%), and gastroesophageal reflux disease (GERD) (2.6%). Therapy effectiveness varied by indication: duodenal ulcer (91%), gastric ulcer (90%), preneoplastic lesions (90%), dyspepsia with normal endoscopy (89%), GERD (88%), and non-investigated dyspepsia (87%). Bismuth-metronidazole-tetracycline and clarithromycin-amoxicillin-bismuth quadruple therapies achieved 90% effectiveness in all indications except GERD. Concomitant clarithromycin-amoxicillin-tinidazole/metronidazole reached 90% cure rates except in patients with non-investigated dyspepsia; whereas sequential clarithromycin-amoxicillin-tinidazole/metronidazole proved optimal (≥90%) in patients with gastric ulcer only. Adverse events were higher in patients treated for dyspepsia with normal endoscopy and duodenal ulcer compared with the remaining indications (23% and 28%, p < 0.001). Therapeutic compliance was higher in patients with duodenal ulcer and preneoplastic lesions (98% and 99%, p < 0.001). CONCLUSION: In Europe, patients with gastric or duodenal ulcers and preneoplastic lesions showed higher H. pylori treatment effectiveness. Bismuth and non-bismuth quadruple therapies achieved optimal results in almost all indications. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02328131.

Bismuth quadruple three-in-one single capsule three times a day increases effectiveness compared with the usual four times a day schedule: results from the European Registry on Helicobacter pylori Management (Hp-EuReg).

BACKGROUND: The recommended schedule for single capsule bismuth quadruple therapy (scBQT, Pylera) includes a proton pump inhibitor (PPI) two times a day and three scBQT capsules four times a day. Four times a day treatments are inconvenient and reduce adherence. In contrast, adherence improves with three times a day schedules. In clinical practice, many gastroenterologists use four capsule scBQT three times a day. However, the effectiveness and safety of this latter approach remain uncertain. AIM: To assess the effectiveness and safety of scBQT administered three times a day in the patients included in the European Registry on Helicobacter pylori Management (Hp-EuReg). METHODS: All Spanish adult patients registered in the Asociación Española de Gastroenterología Research Electronic Data Capture (REDCap) database from June 2013 to March 2021 receiving 10-day scBQT were analysed. Modified intention-to-treat effectiveness, adherence and the safety of scBQT given three times a day were calculated and compared with the four times a day schedule. A multivariate analysis was performed to determine independent factors predicting cure of the infection. RESULTS: Of the 3712 cases, 2516 (68%) were four times a day and 1196 (32%) three times a day. Mean age was 51 years, 63% were women and 15% had a peptic ulcer. The three times a day schedule showed significantly better overall cure rates than four times a day (1047/1112, 94%; 95% CI 92.7 to 95.6 vs 2207/2423, 91%; 95% CI 89.9 to 92.2, respectively, p=0.002). Adherence and safety data were similar for both regimens. In the multivariate analysis, three times a day dosage, first-line therapy, use of standard or high-dose PPIs and adherence over 90% were significantly associated with cure of the infection. CONCLUSIONS: ScBQT prescribed three times a day was more effective than the traditional four times a day schedule. No differences were observed in treatment adherence or safety.

Mistakes in the diagnosis and treatment of Helicobacter pylori infection in daily clinical practice.

BACKGROUND: An adequate diagnostic and therapeutic approach to Helicobacter pylori (H. pylori) infection is the cornerstone to avoid overdiagnosis, overuse of health resources, and increase in antibiotic resistances. The aim of the study was to evaluate the most common errors in clinical practice and the associated risk factors. MATERIALS AND METHODS: This is a retrospective observational study including patients with H. pylori infection and no previous treatment belonging to two defined areas of the National Health System in Spain; some of them were enrolled in the European Registry on H. pylori management (Hp-EuReg). Patients were attended by gastroenterologists between 2010 and 2019. According to current guidelines, we evaluated indications for H. pylori investigation, appropriateness of diagnostic test used in dyspeptic patients and discontinuation of surveillance after treatment. RESULTS: A total of 1730 patients were included, receiving 2260 eradication regimens. H. pylori infection was investigated in 1.7% cases in absence of a formal indication. Oral endoscopy was incorrectly used in 56% of patients with dyspepsia under 55 years without alarm signs, and urea breath test (UBT) was incorrectly used in 22.4% of patients with dyspepsia ≥55 years or red flags. Levofloxacin containing regimens were used as first-line therapy in 7.5% of non-allergic to penicillin patients. After first-line failure, clarithromycin was repeated in 2.6% of the patients who received second-line therapy. Confirmatory test of H. pylori status was absent in 2.5% cases. Men, patients under 55 years, and patients diagnosed by UBT had a higher risk of not undergoing a confirmatory test. CONCLUSIONS: Investigation of H. pylori infection by gastroenterologists is rare in absence of a formal indication; however, endoscopy is commonly used for dyspeptic patients <55 years without red flags and non-invasive tests are still used for dyspeptic patients ≥55 years or presenting alarm signs. Men, patients under 55 years, and patients diagnosed by UBT have an increased risk of being lost to follow-up after eradication treatment.

Is the gender or age of the physician key to a good physician-patient with inflammatory bowel disease relationship?

BACKGROUND AND AIMS: A good patient-physician relationship in inflammatory bowel disease (IBD) is very important and physician empathy is its cornerstone. There is no evidence about if age and/or sex of physicians and patients could influence on perceived empathy by patients. The aim of the study was to assess the level of empathy of IBD specialist physicians perceived by their patients and if it varies according to the age and gender of the patient and the physician. METHODS: We performed a national cross-sectional study based on voluntary online survey to IBD patients that included the Consultation and Relational Empathy (CARE) scale. RESULTS: Five hundred sixty one responses to the survey were received. After applying exclusion criteria, 536 patients were included in the analysis. Total median score of CARE scale was 44.5 (maximum possible score: 50 points). Most of the patients (99.1%) considered the contents of the questionnaire to be an important issue. There were no significant differences in CARE scale scores in function of patient/physician age range or gender [physician gender: males vs. females: median 46 vs. 44, p=0.139; physician age: <40 years, 40-60 years, >60 years: 45.5 vs. 44 vs. 44, p=0.328]. CONCLUSION: Spanish inflammatory bowel disease patients have a great physician empathy perception, which is the key to a good patient-physician relationship, and this fact is not influenced by age or gender of patients or inflammatory bowel disease specialist.

Effectiveness of the cervical pessary for the prevention of preterm birth in singleton pregnancies with a short cervix: a meta-analysis of randomized trials.

OBJECTIVE: To assess the efficacy of cervical pessary application for the prevention of spontaneous preterm birth (SPB) in singleton pregnancies with a sonographically measured short cervix. METHODS: Searches were conducted in PubMed-Medline, Embase, Scopus, Web of Science, and Cochrane Library, and clinical trial registries for randomized controlled trials (RCTs) published in all languages from inception through 28 July 2018. Inclusion criteria were registered RCTs of singleton pregnants with a short cervix (≤ 25 mm) measured at 22-24 weeks comparing the use of a cervical pessary versus controls over the risk of SPB. Risk of bias was evaluated with the Cochrane tool. Risk ratios (RRs) and mean differences and 95% confidence intervals (CIs) were calculated. RESULTS: We identified three RCTs meeting defined inclusion criteria, including a total of 1612 pregnancies (805 used a cervical pessary). SPB risk at < 37 was lower for participants using the pessary (RR 0.46; 95% CI 0.28-0.77). Pessary application was associated with a higher risk of presenting vaginal discharge (RR 2.05; 95% CI 1.82-2.31). There were no significant differences between pessary users and controls in terms of SPB at < 28 and < 34 weeks, and for any type of preterm birth < 34 weeks; mean gestational age and infant weight at delivery; and the risks of chorioamnionitis, cesarean delivery, and perinatal or neonatal outcomes. Sub-analysis by risk of bias showed that there was a lower risk of SPB < 34 weeks (RR 0.33; 95% CI 0.16-0.66) in two RCTs with low risk of bias. CONCLUSION: Cervical pessary application was associated with a reduced risk of SPB at < 37 weeks and a higher risk of vaginal discharge.

Systematic review and meta-analysis of Spanish studies regarding the association between maternal 25-hydroxyvitamin D levels and perinatal outcomes.

Objective: This systematic review and meta-analysis of Spanish studies assessed the association of maternal 25-hydroxyvitamin D [25(OH)D] levels on perinatal outcomes. Methods: PubMed, Cochrane Library, Embase, Scielo, Scopus, and Web of Science research databases were searched from inception through December 30 2017 using the terms 'vitamin D', 'pregnancy', and 'Spain'. Studies that compared first or second half of pregnancy normal 25(OH)D (≥30.0 ng/mL) versus insufficient (20.0-29.9 ng/mL) or deficient (<20.0 ng/mL) circulating levels and perinatal outcomes were systematically extracted. Data are presented as pooled odds ratios and their 95% confidence intervals (CIs) for categorical variables or mean differences and CIs for continuous variables. Risk of bias was evaluated with the Newcastle-Ottawa Scale. Results: Five cohort studies met inclusion criteria. The risk of gestational diabetes mellitus, preeclampsia, preterm birth, and small-for-gestational-age infants, and birthweight was not influenced by first half of pregnancy maternal 25(OH)D levels. In addition, second half of pregnancy 25(OH) levels did not affect birthweight. Conclusion: Maternal 25(OH)D levels during pregnancy did not affect studied perinatal outcomes and birthweight.

Endometriosis and gestational diabetes mellitus risk: a systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review and meta-analysis regarding endometriosis and the risk of gestational diabetes mellitus (GDM). METHODS: We carried out a search of the following databases: Medline, Embase, Web of Science, Cochrane Library, Scopus, Scielo, Clinicaltrials.gov, the UK Clinical Trials Gateway, and the Australian New Zealand Clinical Trials Registry, from inception through April 28 2017, without language restrictions, in order to evaluate the effect of endometriosis over GDM risk, in women with and without endometriosis. Odds ratios (ORs) and their 95% confidence intervals (CIs) or mean differences (MDs) were calculated as effects. Methodological quality of evidence was assessed with the Newcastle-Ottawa Scale, and heterogeneity among studies with the I2 statistic. Random-effects models were used for meta-analyses, and publication bias was assessed with Egger's test. RESULTS: We identified 12 studies (10 cohort and two case control studies) with a total of 48,762 pregnancies, including 3,461 with endometriosis. Endometriosis had no significant effect on GDM risk (OR =1.14; 95% CI: 0.86, 1.51; p = .35, I2 = 56%, Egger's test p = .45). Secondary outcomes (gestational age at delivery, birthweight, and Neonatal Intensive Care Unit admission) were statistically similar in women with and without endometriosis. CONCLUSIONS: Better-designed studies are needed to confirm our results.

Single versus double-balloon catheters for the induction of labor of singleton pregnancies: a meta-analysis of randomized and quasi-randomized controlled trials.

OBJECTIVE: To compare the efficacy of single- versus double-balloon catheter (SBC vs. DBC) for cervical ripening and labor induction with an unfavorable cervix. METHODS: Systematic review and meta-analysis of randomized controlled trials (RCTs) or quasi-RCTs (qRCT) regarding the use of SBC or DBC for labor induction of live singleton cephalic pregnancies (≥ 35 weeks) of any parity with an unripe cervix (Bishop score ≤ 6). Nine research databases were searched for original articles published in all languages up to November 2017 comparing both devices for labor induction. Five RCTs and one qRCT were included. Primary outcome measures were time from intervention (device placement) to birth time, vaginal delivery and cesarean section rates, and maternal satisfaction with the procedure. Risk of bias was evaluated with the Cochrane tool. Random effects models were used to combine data for meta-analyses. Summary measures were reported as mean differences and risk ratios (RR) with 95% confidence intervals. RESULTS: Regardless of parity, pooled analyses of the six trials (n = 1060 women) found that mean intervention to birth time, vaginal delivery and cesarean section rates, and maternal satisfaction to the procedure were similar for both studied groups (SBC vs. DBC). CONCLUSION: Measured primary outcome measures were similar regardless of the type of device used for labor induction of singleton pregnancies.

Uterine or paracervical lidocaine application for pain control during intrauterine contraceptive device insertion: a meta-analysis of randomised controlled trials.

OBJECTIVE: Systematic review and meta-analysis to assess the effects of uterine or paracervical lidocaine application on pain control during IUD insertion. METHODS: PubMed and five other electronic research databases were searched through 15 November 2017 for RCTs comparing lidocaine treatment vs. a control (placebo or no-intervention) to prevent pain during IUD insertion. Searched terms included 'IUD insertion', 'lidocaine' and 'randomised controlled trial'. RCTs evaluating lidocaine treatment before IUD insertion without restriction of language, age and IUD type. Pain measured by visual pain scales at tenaculum placement, IUD insertion and immediate post-IUD insertion. Results of random effects meta-analyses were reported as mean differences (MDs) of visual pain scale (VPS) scores and their 95% confidence intervals (CIs). RESULTS: Eleven RCTs (n = 1458 women) reporting paracervical lidocaine block or uterine mucosa lidocaine application before IUD insertion. Lidocaine produced lower VPS scores during tenaculum placement (MD -0.99, 95% CI: -1.73 to -0.26), IUD insertion (MD -1.26, 95% CI: -2.23 to -0.29) and immediate post-IUD insertion period (MD -1.25, 95% CI: -2.17 to -0.33). CONCLUSION: Lidocaine treatment was associated with modest reduction of pain during tenaculum placement and after IUD insertion.

The role of vitamin C in the prevention of pancreatic cancer: a systematic-review.

Introduction and aim: The aim of this systematic review was to assess the role of vitamin C in the prevention of pancreatic cancer (PC). Methods: A comprehensive literature search was performed in PubMed, Embase and Web of Science up to August 2023, to identify randomized controlled trials (RCT), cohort studies and mendelian randomization studies based on prospective databases assessing the role of vitamin C in PC prevention. Results: A total of twelve studies including European and North-American participants were included: two RCT, three mendelian randomization (MR) studies and seven cohort studies. Both RCT showed high quality in Cochrane risk of bias tool. Only one cohort study had <7 points in Newcastle Ottawa Scale. Both RCT found no association between the intake of 500 mg/day of vitamin C and the incidence of PC. Only one prospective cohort study found an association between vitamin C serum levels and a lower incidence of PC. The remaining cohort studies and MR studies found no association between dietary/supplements intake of vitamin C or circulating vitamin C levels and the incidence of PC. Conclusion: There is no supporting evidence that vitamin C prevents PC development. Future prospective quality studies including high-risk populations are needed.

The role of filgotinib in ulcerative colitis and Crohn's disease.

Filgotinib is an oral small molecule that selectively inhibits JAK1. It is already approved for the treatment of moderately to severely active ulcerative colitis (UC). Ongoing studies are evaluating the efficacy and safety of filgotinib in Crohn's disease (CD). The purpose of this review is to summarize the available data regarding filgotinib in the management of UC and CD. We used Pubmed, Embase and clinicaltrials.gov websites to search all available data and currently ongoing studies regarding the efficacy and safety of filgotinib in inflammatory bowel diseases. Filgotinib is an effective and safe drug for the management of biologic-naive and biologic-experienced patients with moderate-to-severe UC. The same efficacy results have not been achieved in CD.

Filgotinib is an oral medication that inhibits the activity of the JAK1 enzyme. It has received approval from the European Medicines Agency for the treatment of moderate-to-severe ulcerative colitis, a condition characterized by inflammation in the lower part of the digestive tract. Filgotinib has a rapid mechanism of action and is effective at relieving the symptoms of ulcerative colitis and maintaining this improvement. However, its use is recommended with caution in patients who have risk factors such as heart and blood vessel issues, active smoking, a history of cancer, or those who are elderly (over 65 years old), and only when there are no other viable treatment options available. Although filgotinib was also studied for managing moderate-to-severe Crohn's disease, a chronic inflammatory condition affecting the digestive system, it did not pass phase III clinical trials and will not be available for this indication.

Cardiovascular risk assessment in inflammatory bowel disease with metabolic dysfunction-associated steatotic liver disease.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) has been reported to increase the risk of early atherosclerosis even in young patients. Moreover, metabolic dysfunction-associated steatotic liver disease (MASLD), which has been linked to IBD, is a well-recognized but underdiagnosis entity related to cardiovascular risk. We analyze the impact of MASLD in IBD patients' cardiovascular risk through both advanced lipoprotein profile sorted by nuclear magnetic resonance spectroscopy, and carotid artery intima-media thickness (CIMT). METHODS: Cross-sectional cohort study which involves 941 IBD adult outpatients. Of them, 50 patients with IBD who met criteria for MASLD and 50 with IBD without MASLD, matched by sex and age were included. Alterations in CIMT were evaluated considering abnormal measures above the 75th percentile adjusted for sex and age. Specific advanced lipoprotein profile was also carried out. RESULTS: Most of the patients had an abnormal CIMT (58%). MASLD (OR=5.05, CI 95%=1.71-14.92) and female sex (OR=3.32, CI 95%=1.03-10) were significantly associated with CIMT alterations. Dense LDL particles (with high cholesterol composition in general cohort (OR=3.62, 95% CI=1.07-12.19) and high triglycerides density in young subgroup (OR=6.25, 95% CI=1.04-50) but not total LDL cholesterol were associated with CIMT alterations. CONCLUSIONS: MASLD and female sex are associated with early atherosclerosis in IBD patients. Dense LDL particle in combination with vascular imaging findings should be evaluated as non-invasive tools in the management of cardiovascular risk in IBD patients.

Crohn´s disease is an independent risk factor for liver fibrosis in patients with inflammatory bowel disease and non-alcoholic fatty liver disease.

BACKGROUND AND AIMS: Controversial data have been reported regarding the prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD) in Inflammatory Bowel Disease (IBD) population and IBD-related risk factors. The aim of the study was to assess the prevalence and risk factors associated with NAFLD and liver fibrosis in IBD participants compared with non-IBD controls. METHODS: Cross-sectional, case-control study including 741 IBD cases and 170 non-IBD controls, matched by sex and age. All participants underwent liver ultrasound, transient elastography and laboratory tests. A logistic regression multivariable analysis was performed adjusting for classic metabolic risk factors and history of systemic steroid use. RESULTS: The prevalence of NAFLD and significant liver fibrosis was 45 % and 10 % in IBD group, and 40 % and 2.9 % in non-IBD group (p = 0.255 and 0.062, respectively). Longer IBD duration (aOR 1.02 95% CI (1.001-1.04)) and older age at IBD diagnosis (aOR 1.02 95 % CI (1.001-1.04)) were independent risk factors for NAFLD in IBD group. Crohn´s Disease was an independent risk factor for significant liver fibrosis in participants with IBD and NAFLD (aOR 3.97 95 % CI (1.78-8.96)). NAFLD occurred at lower BMI levels in IBD group with NAFLD compared to non-IBD group with NAFLD (aOR 0.92 95 % CI (0.87-0.98)). CONCLUSIONS: Although we found no differences in the prevalence of NAFLD and liver fibrosis between IBD group and non-IBD group, our findings suggest that liver fibrosis progression should be closely monitored in patients with concomitant CD and NAFLD, more in particular in those with long standing active disease.

Role of proton pump inhibitors dosage and duration in Helicobacter pylori eradication treatment: Results from the European Registry on H. pylori management.

BACKGROUND: Management of Helicobacter pylori (H. pylori) infection requires co-treatment with proton pump inhibitors (PPIs) and the use of antibiotics to achieve successful eradication. AIM: To evaluate the role of dosage of PPIs and the duration of therapy in the effectiveness of H. pylori eradication treatments based on the 'European Registry on Helicobacter pylori management' (Hp-EuReg). METHODS: Hp-EuReg is a multicentre, prospective, non-interventionist, international registry on the routine clinical practice of H. pylori management by European gastroenterologists. All infected adult patients were systematically registered from 2013 to 2022. RESULTS: Overall, 36,579 patients from five countries with more than 1000 patients were analysed. Optimal (≥90%) first-line-modified intention-to-treat effectiveness was achieved with the following treatments: (1) 14-day therapies with clarithromycin-amoxicillin-bismuth and metronidazole-tetracycline-bismuth, both independently of the PPI dose prescribed; (2) All 10-day (except 10-day standard triple therapy) and 14-day therapies with high-dose PPIs; and (3) 10-day quadruple therapies with clarithromycin-amoxicillin-bismuth, metronidazole-tetracycline-bismuth, and clarithromycin-amoxicillin-metronidazole (sequential), all with standard-dose PPIs. In first-line treatment, optimal effectiveness was obtained with high-dose PPIs in all 14-day treatments, in 10- and 14-day bismuth quadruple therapies and in 10-day sequential with standard-dose PPIs. Optimal second-line effectiveness was achieved with (1) metronidazole-tetracycline-bismuth quadruple therapy for 14- and 10 days with standard and high-dose PPIs, respectively; and (2) levofloxacin-amoxicillin triple therapy for 14 days with high-dose PPIs. None of the 7-day therapies in both treatment lines achieved optimal effectiveness. CONCLUSIONS: We recommend, in first-line treatment, the use of high-dose PPIs in 14-day triple therapy and in 10-or 14-day quadruple concomitant therapy in first-line treatment, while standard-dose PPIs would be sufficient in 10-day bismuth quadruple therapies. On the other hand, in second-line treatment, high-dose PPIs would be more beneficial in 14-day triple therapy with levofloxacin and amoxicillin or in 10-day bismuth quadruple therapy either as a three-in-one single capsule or in the traditional scheme.

Role of compliance in Helicobacter pylori eradication treatment: Results of the European Registry on H. pylori management.

BACKGROUND: Adherence to Helicobacter pylori (H. pylori) eradication treatment is a cornerstone for achieving adequate treatment efficacy. OBJECTIVE: To determine which factors influence compliance with treatment. METHODS: A systematic prospective non-interventional registry (Hp-EuReg) of the clinical practice of European gastroenterologists. Compliance was considered adequate if ≥90% drug intake. Data were collected until September 2021 using the AEG-REDCap e-CRF and were subjected to quality control. Modified intention-to-treat analyses were performed. Multivariate analysis carried out the factors associated with the effectiveness of treatment and compliance. RESULTS: Compliance was inadequate in 646 (1.7%) of 38,698 patients. The non-compliance rate was higher in patients prescribed longer regimens (10-, 14-days) and rescue treatments, patients with uninvestigated dyspepsia/functional dyspepsia, and patients reporting adverse effects. Prevalence of non-adherence was lower for first-line treatment than for rescue treatment (1.5% vs. 2.2%; p < 0.001). Differences in non-adherence in the three most frequent first-line treatments were shown: 1.1% with proton pump inhibitor + clarithromycin + amoxicillin; 2.3% with proton pump inhibitor clarithromycin amoxicillin metronidazole; and 1.8% with bismuth quadruple therapy. These treatments were significantly more effective in compliant than in non-compliant patients: 86% versus 44%, 90% versus 71%, and 93% versus 64%, respectively (p < 0.001). In the multivariate analysis, the variable most significantly associated with higher effectiveness was adequate compliance (odds ratio, 6.3 [95%CI, 5.2-7.7]; p < 0.001). CONCLUSIONS: Compliance with Helicobacter pylori eradication treatment is very good. Factors associated with poor compliance include uninvestigated/functional dyspepsia, rescue-treatment, prolonged treatment regimens, the presence of adverse events, and the use of non-bismuth sequential and concomitant treatment. Adequate treatment compliance was the variable most closely associated with successful eradication.

Symptomatic gallstone disease: Recurrence patterns and risk factors for relapse after first admission, the RELAPSTONE study.

BACKGROUND: Delayed cholecystectomy in patients with symptomatic gallstone disease is associated with recurrence. Limited data on the recurrence patterns and the factors that determine them are available. OBJECTIVE: We aimed to determine the pattern of relapse in each symptomatic gallstone disease (acute pancreatitis, cholecystitis, cholangitis, symptomatic choledocholithiasis, and biliary colic) and determine the associated factors. METHODS: RELAPSTONE was an international multicenter retrospective cohort study. Patients (n = 3016) from 18 tertiary centers who suffered a first episode of symptomatic gallstone disease from 2018 to 2020 and had not undergone cholecystectomy during admission were included. The main outcome was relapse-free survival. Kaplan-Meier curves were used in the bivariate analysis. Multivariable Cox regression models were used to identify prognostic factors associated with relapses. RESULTS: Mean age was 76.6 [IQR: 59.7-84.1], and 51% were male. The median follow-up was 5.3 months [IQR 2.1-12.4]. Relapse-free survival was 0.79 (95% CI: 0.77-0.80) at 3 months, 0.71 (95% CI: 0.69-0.73) at 6 months, and 0.63 (95% CI: 0.61-0.65) at 12 months. In multivariable analysis, older age (HR = 0.57; 95% CI: 0.49-0.66), sphincterotomy (HR = 0.58, 95% CI: 0.49-0.68) and higher leukocyte count (HR = 0.79; 95% CI: 0.70-0.90) were independently associated with lower risk of relapse, whereas higher levels of alanine aminotransferase (HR = 1.22; 95% CI: 1.02-1.46) and multiple cholelithiasis (HR = 1.19, 95% CI: 1.05-1.34) were associated with higher relapse rates. CONCLUSION: The relapse rate is high and different in each symptomatic gallstone disease. Our independent predictors could be useful for prioritizing patients on the waiting list for cholecystectomies.

Risk of Cancer in Patients with Inflammatory Bowel Diseases and Keys for Patient Management.

Chronic inflammation in patients with Inflammatory Bowel Disease (IBD) leads to an increased risk of colorectal cancer, small bowel cancer, intestinal lymphoma and cholangiocarcinoma. However, treatments for IBD have also been associated with an increased risk of neoplasms. Patients receiving Thiopurines (TPs) have an increased risk of hematologic malignancies, non-melanoma skin cancer, urinary tract neoplasms and cervical cancer. Anti-TNFs have been associated with a higher risk of neoplasms, mainly lymphomas and melanomas; however, the data are controversial, and some recent studies do not confirm the association. Nevertheless, other biologic agents, such as ustekinumab and vedolizumab, have not shown an increased risk of any neoplasm to date. The risk of malignancies with tofacitinib exists, but its magnitude and relationship with previous treatment with TPs is not defined, so more studies from daily clinical practice are needed. Although biologic therapy seems to be safe for patients with current cancer or a prior history of cancer, as has been demonstrated in other chronic inflammatory conditions, prospective studies in this specific population are needed. Until that time, it is crucial to manage such conditions via the combined clinical expertise of the gastroenterologist and oncologist.

Liver Fibrosis in Non-Alcoholic Fatty Liver Disease and Progression to Hepatocellular Carcinoma in Patients with Inflammatory Bowel Disease: A Systematic Review.

The aim of the systematic review is to assess the prevalence and risk factors of liver fibrosis in patients with Inflammatory Bowel Disease (IBD) and Non-Alcoholic Fatty Liver Disease (NAFLD) and to discuss the role of liver fibrosis in the progression to hepatocellular carcinoma (HCC). We performed a structured search in PubMed, Web of Science, Embase, and Scopus up to 3 March 2023 to identify observational studies reporting liver fibrosis in patients with NAFLD and IBD. Quality of studies was assessed using the Newcastle-Ottawa Scale (NOS) score. A total of 23 studies met our inclusion criteria, including 629,781 patients. A total of 10 cross-sectional, 3 case-control, and 10 cohort studies were included. Fourteen studies had a NOS score ≥ 7 points. NAFLD was diagnosed in 2162/6332 (34.1%) IBD participants. However, NAFLD diagnosis was established in 924/2962 (31.2%) healthy individuals without IBD. Advanced liver fibrosis was found in 116 (11.6%) of 992 IBD patients with NAFLD. Most studies found an association between NAFLD and classic cardiovascular risk factors such as older age, male sex, higher BMI, diabetes, hypertension and dyslipidemia. In addition, metabolic syndrome features were also associated with an increased risk of significant and advanced liver fibrosis. Although no strong association between NAFLD and IBD therapy was reported, some studies associated NAFLD with IBD diagnosis, Crohn's Disease, a complicated course of IBD, disease activity, and IBD duration. Advanced liver fibrosis was also associated with Crohn's disease in several studies. In conclusion, NAFLD and advanced liver fibrosis are prevalent and clinically relevant extraintestinal manifestations, so its diagnosis and potential progression to HCC should be carefully considered in daily clinical practice.

Inflammatory Bowel Disease Is an Independent Risk Factor for Metabolic Dysfunction-Associated Steatotic Liver Disease in Lean Individuals.

BACKGROUND: Despite classical association between metabolic dysfunction-associated steatotic liver disease (MASLD) and obesity, there is increasing evidence on the development of MASLD in lean individuals. The aim of the study was to assess the prevalence and risk factors of MASLD and significant liver fibrosis in lean participants with inflammatory bowel disease (IBD). METHODS: This was a cross-sectional, case-control study including 300 lean cases with IBD and 80 lean controls without IBD, matched by sex and age. All participants underwent a liver ultrasound, transient elastography, and laboratory tests. RESULTS: The lean IBD group showed a significantly higher prevalence of MASLD compared with lean non-IBD group (21.3% vs 10%; P = .022), but no differences were observed in the prevalence of significant liver fibrosis (4.7% vs 0.0%; P = 1.000). No differences were found between the prevalence of MASLD in IBD and non-IBD participants who were overweight/obese (66.8% vs 70.8%; P = .442). In addition, the prevalence of MASLD was significantly higher in the overweight/obese IBD group compared with the lean IBD group (P < .001). IBD was an independent risk factor for MASLD in lean participants (odds ratio [OR], 2.71; 95% confidence interval [CI], 1.05-7.01; P = .04), after adjusting for classic metabolic risk factors and prior history of systemic steroid use. Nevertheless, no association between IBD related factors and MASLD was identified in lean IBD participants. When the overweight/obese and lean IBD groups with MASLD were compared, the overweight/obese IBD group with MASLD showed higher levels of the homeostatic model assessment of insulin resistance (OR, 1.49; 95% CI, 1.11-1.98; P = .007) and history of smoking (OR, 4.66; 95% CI, 1.17-18.49; P = .029). CONCLUSIONS: MASLD prevalence was higher in the lean IBD group compared with lean non-IBD group, independent of classic metabolic risk factors.

Lifestyle Can Exert a Significant Impact on the Development of Metabolic Complications and Quality Life in Patients with Inflammatory Bowel Disease.

Inflammatory bowel diseases (IBDs) are associated with an increased risk of metabolic comorbidities. There is a lack of data regarding the relationship between lifestyle and metabolic diseases in IBD patients. A cross-sectional study on consecutive IBD outpatients was conducted. Adherence to the Mediterranean diet (MD) was assessed using a 14-item questionnaire from the PREDIMED study, and physical activity was evaluated using the GODIN-Leisure score. Body composition was studied based on body mass index and waist-hip ratio (WHR), while quality of life was assessed using a nine-item short questionnaire. Among the 688 evaluated IBD patients, 66% were overweight or obese, 72.7% did not lead an active lifestyle and 70.1% did not adhere to the MD. Metabolic syndrome was associated with age (OR = 1.07, p = 0.019), overweight/obesity (OR = 12.987, p < 0.001) and the inflammatory behavior of Crohn's disease (OR = 6.172, p = 0.001). Type 2 diabetes mellitus or prediabetes was associated with age (OR = 1.063 p = 0.016), overweight/obesity (OR = 3.861, p < 0.001) and the inflammatory behavior of Crohn's disease (OR = 4.716, p = 0.001). Overweight /obesity (OR = 5.494, p < 0.001), a high WHR (OR = 2.564, p = 0.005) and a non-active lifestyle (OR = 2.202, p = 0.0003) were associated with metabolic dysfunction-associated steatotic liver disease. Lifestyle, body composition and not solely systemic inflammation might exert a significant influence on the emergence of metabolic comorbidities such as MASLD, type 2 diabetes mellitus and metabolic syndrome in patients with IBD.