Search

Background: Endoscopic retrograde cholangiopancreatography (ERCP) still has a relatively high complication rate, underscoring the importance of high-quality training. Despite existing guidelines, real-world data on training conditions remain limited. This pan-European survey aims to systematically explore the perceptions surrounding ERCP training., Methods: A survey was distributed through the friends of United European Gastroenterology (UEG) Young Talent Group network to physicians working in a UEG member or associated states who regularly performed ERCPs., Results: Of 1035 respondents from 35 countries, 649 were eligible for analysis: 228 trainees, 225 trainers, and 196 individuals who regularly performed ERCP but were neither trainees nor trainers. The mean age was 43 years, with 72.1% identifying as male, 27.6% as female, and 0.3% as non-binary. The majority (80.1%) agreed that a structured training regimen is desirable. However, only 13.7% of trainees and 28.4% of trainers reported having such a structured program in their institutions. Most respondents (79.7%) supported the concept of concentrating training in centers meeting specific quality metrics, with 64.1% suggesting a threshold of 200 annual ERCPs as a prerequisite. This threshold revealed that 36.4% of trainees pursued training in lower-volume centers performing <200 ERCPs annually. As many as 70.1% of trainees performed <50 annual ERCPs, whereas only 5.0% of trainers performed <50 ERCPs annually. A low individual trainee caseload (<50 ERCPs annually) was more common in lower-volume centers than in higher-volume centers (82.9% vs. 63.4%)., Conclusions: The first pan-European survey investigating ERCP training conditions reveals strong support for structured training and the concentration of training efforts within centers meeting specific quality metrics. Furthermore, this survey exposes the low availability of structured training programs with many trainees practicing at lower-volume centers and 71% of all trainees having little hands-on exposure. These data should motivate to standardize ERCP training conditions further and ultimately improve patient care throughout Europe., (© 2024 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Introduction: A proper sample size calculation enables to conduct adequately powered randomized controlled trials (RCTs) and to provide a valid assessment of a specific clinical question., Areas Covered: In the current manuscript, we tried to provide the reader with an easy guide on the principles of sample size calculation in RCTs, tailored specifically to the context of gastroenterology and hepatology. The basics of sample size calculation were commented with a description of some of the main methods, including the calculation of the non-inferiority margin for non-inferiority RCTs and the calculation of the minimum clinically important difference (MCID). Some examples from the gastroenterology literature were also provided., Expert Opinion: Collaborating with a biostatistician can provide valuable insights into the nuances of sample size calculation and study design. However, it is crucial that the clinicians understand the basics of calculating sample size, so they could provide valuable input in designing the study from a clinical point of view.

Neutrophils play a significant role in sustaining chronic inflammation in Inflammatory Bowel Disease. The intestinal basement membrane acts as a barrier for immunological homeostasis, where the α3 and α4 chains of type IV collagen are expressed on the mucosal surface. We wanted to develop a biomarker reflecting early tissue injury, providing an opportunity for intervention. Two competitive enzyme-linked immunosorbent assays (ELISAs) quantifying human neutrophil elastase (HNE) degraded neo-epitopes of COL4A3 and COL4A4 were developed and investigated in two observational cohorts (n = 161, n = 100). A biomarker of MMP-mediated degradation of COL4A1 (C4M) was used for comparison. In Cohort 1, patients with mild endoscopic ulcerative colitis showed elevated levels of C4A3-HNE compared to those with severe disease. C4M had a strong positive correlation with disease activity. C4A3-HNE/C4M provided superior discrimination between mild and severe endoscopic disease and negatively correlated to disease activity. In Cohort 2, C4A4-HNE and C4A4-HNE/C4M showed similar trends. C4A3-HNE and C4A4-HNE possibly reflect early intestinal tissue injury. Combining the markers with a biomarker of another α-chain of the same collagen provides information on two distinct stages of mucosal damage. These biomarkers may be used to monitor disease flare-up in patients in remission, reducing the need for frequent endoscopic procedures., (© 2024. The Author(s).)

Chronic inflammation in inflammatory bowel disease (IBD) triggers significant extracellular matrix remodeling, including elastin remodeling, leading to severe clinical complications. Novel methods to assess intestinal tissue destruction may act as surrogate markers of endoscopic disease activity, relieving patients of invasive endoscopy. We explored the noninvasive blood-based biomarkers ELP-3 and ELM-12, measuring elastin degradation in IBD. In a study involving 104 Crohn's disease (CD), 39 ulcerative colitis (UC), and 29 healthy donors, we assessed these biomarkers' association with endoscopic and clinical disease activity using ELISA. Patients were evaluated based on the SES-CD and CDAI for CD patients and modified MES and partial Mayo for UC patients. ELP-3 and ELM-12 were elevated in patients with IBD. Discerning CD patients in endoscopic remission and mild from moderate to severe, ELP-3 provided an AUC of 0.69 and ELM-12 an AUC of 0.73. The ELP-3 biomarker was associated with UC patients and provided the highest diagnostic power of 0.87 for remission vs. active clinical disease. The data suggest an association of ELP-3 with active CD and ELM-12 with endoscopic remission in CD patients. Additionally, ELP-3 could identify UC patients with active clinical disease from patients in remission. The noninvasive biomarkers ELP-3 and ELM-12 could be potential surrogate biomarkers of elastin degradation and endoscopic and clinical disease markers.

Extracellular matrix (ECM) homeostasis is highly affected in active inflammatory bowel disease (IBD). The aim of the study was to investigate serological biomarkers of type III, IV, and V collagen degradation and formation, and their association with disease activity in IBD. ECM remodeling serum biomarkers were measured in 162 IBD patients, 110 with Crohn's disease (CD) and 52 with ulcerative colitis (UC), and in 29 healthy donors. Biomarkers of type III collagen degradation (C3M) and formation (PRO-C3), type IV collagen degradation (C4M) and formation (PRO-C4), and type V collagen formation (PRO-C5) were measured using ELISA. Inflammatory activity was assessed using endoscopic, clinical, and biochemical activity indices. The highest diagnostic value was identified in discriminating endoscopically moderate to severe disease in CD (PRO-C3, C3M/PRO-C3, and C4M with AUC of 0.70, 0.73, and 0.69, respectively) and UC (C3M, C3M/PRO-C3, and C4M with AUC of 0.86, 0.80, and 0.76, respectively). C4M and C3M/PRO-C3 in combination yielded AUC of 0.93 (0.66-0.90) in CD and 0.94 (0.65-0.99) in UC. This study confirmed that ECM remodeling reflected disease activity in CD and UC. A combination of C4M, C3M, and PRO-C3 biomarkers may potentially be considered as a biomarker differentiating moderate to severe endoscopic disease.

Background: There is currently scarce knowledge about markers of early therapeutic response in patients with inflammatory bowel disease (IBD) treated with biologics. The aim of this study was to evaluate the role of fecal calprotectin (FC) as an early predictor of mucosal healing and clinical remission., Methods: Data from a multicenter series of 172 IBD patients treated with biologics between 2017 and 2020 were analyzed. Treatment outcomes were mucosal healing and clinical remission assessed at 2 years. FC levels were assessed at 14 weeks (post-induction), at 6 months, and yearly. The receiver operating characteristic (ROC) curve analysis was performed to calculate the best cut-off in % change of FC levels between post-induction and baseline predicting treatment outcomes. Sensitivity, specificity, and accuracy for several post-induction FC cut-off points were also calculated., Results: At 2 years, mucosal healing was noted in 77 patients (44.7%), of whom were 41 Crohn's disease (CD) and 36 ulcerative colitis (UC) patients, whereas 106 patients experienced clinical remission (61.6%), of whom were 59 CD and 47 UC patients. Both baseline and post-induction FC levels were significantly higher in non-responders as compared to responders. On the other hand, FC decrease was less pronounced in non-responders. Similar results were observed in all subgroups, namely according to disease (CD vs. UC), or treatment used (TNF-inhibitors vs. vedolizumab). The best cut-off points were -86% in % change in FC levels to predict mucosal healing and -83% for clinical remission., Conclusions: The current study suggests a predictive role of post-induction FC assessment to predict treatment response in IBD patients treated with biologics.

There is limited evidence on the incidence of needle tract seeding (NTS) in patients undergoing endoscopic ultrasound (EUS) tissue acquisition (TA) of pancreatic lesions. This meta-analysis aimed to assess the incidence of NTS after EUS-TA. With a search of the literature up until April 2022, we identified 10 studies (13,238 patients) assessing NTS incidences in patients undergoing EUS-TA. The primary outcome was NTS incidence. The secondary outcome was a comparison in terms of peritoneal carcinomatosis incidence between patients who underwent EUS-TA and non-sampled patients. Results were expressed as pooled rates or odds ratio (OR) and 95% confidence intervals (CI). The pooled rate of NTS was 0.3% (95% CI 0.2-0.4%), with no evidence of heterogeneity (I 2 = 0%). Subgroup analysis based on the type of sampled lesion confirmed this finding both in patients with pancreatic adenocarcinoma (0.4%, 0.2-0.6%) and in patients with cystic pancreatic lesions (0.3%, 0.1-0.5%). No difference in terms of metachronous peritoneal dissemination was observed between patients who underwent EUS-TA and non-sampled patients (OR 1.02, 0.72-1.46; p = 0.31), with evidence of low heterogeneity (I 2 = 16%). Rates of NTS after EUS-TA are very low; therefore, EUS-TA could be safely performed in a pre-operative setting.

A 48-year-old female patient presented with longstanding unrecognized celiac disease (CD), a family history of CD, and a short duration of alarming symptoms. The diagnostic evaluation revealed the concomitant presence of small and large bowel ulcers raised a dilemma about differential diagnosis in her case. Pathologic examination of tissue specimens from the jejunal ulcer led to the diagnosis of enteropathy-associated T-cell lymphoma. In recent years, the availability of modern cross-sectional imaging and endoscopy modalities has dramatically improved the detection and characterization of small bowel lesions. Characterization of small bowel ulcers by endoscopy and radiology imaging in a patient with suspected complicated CD (CCD) needs to be made in conjunction with all clinical factors, as there is a wide overlap of the possible etiologic factors. Enteropathy-associated T-cell lymphoma is a highly aggressive T-cell lymphoma with a poor prognosis, since early diagnosis and appropriate treatment may be delayed due to nonspecific clinical and endoscopic presentation. Therefore, it is crucial to timely recognize patients with suspected CCD and properly navigate diagnostic imaging tools, acquire adequate biopsy, and perform immunophenotyping to set early diagnosis in patients with diffuse intestinal ulcers and CD., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Background and Objective : This study was conducted to evaluate the diagnostic performance of various biomarkers for steatosis, fibrosis, and inflammation in comparison to a liver biopsy (LB) in patients with nonalcoholic fatty liver disease (NAFLD). Materials and Methods: This was a cross-sectional study that included 135 patients with biopsy-proven NAFLD. Fatty liver index (FLI), hepatic steatosis index (HSI), cell death markers (CK-18 M30 and CK-18 M65), FIB-4 index, NAFLD fibrosis score (NFS), BARD, and AST to platelet ratio index (APRI) were calculated and analysed. Results: FLI, HSI scores, and the cell death biomarkers showed poor diagnostic accuracy for steatosis detection and quantification, with an area under the curve (AUC) of <0.70. The cell death biomarkers likewise did not perform well for the detection of nonalcoholic steatohepatitis (NASH) (AUC < 0.7). As for the fibrosis staging, only APRI and the cell death biomarkers had moderate accuracy (AUC > 0.7) for advanced fibrosis, whereas FIB-4, BARD, and NFS scores demonstrated poor performance (AUC < 0.70). However, a combination of FIB-4 and NFS with the cell death biomarkers had moderate accuracy for advanced (≥F3) fibrosis detection, with an AUC of >0.70. Conclusions: In this first study on Croatian patients with NAFLD, serum biomarkers demonstrated poor diagnostic performance for the noninvasive diagnosis of liver steatosis and NASH. APRI and the cell death biomarkers had only moderate accuracy for diagnosing advanced fibrosis, as did the combination of FIB-4 and NFS with the cell death biomarkers. Further studies regarding serum biomarkers for all NAFLD stages are needed.

Introduction: The pandemic of obesity is strongly related to increase of chronic kidney disease (CKD) prevalence. The currently recommended CKD epidemiology collaboration (CKD EPI) equation has several serious limitations, particularly in obese subjects who have high body surface area (BSA). The aim of our study was to analyze differences in the prevalence of CKD between CKD EPI and de-indexed equations where individual BSA was used., Methods: In a total of 2,058 subjects (random sample from a general rural population, 29.65% obese), BSA was estimated using DuBois and DuBois and Moesteller equations and included into the de-indexed equations (CKD DBi, CKD Mi). CKD was classified according to the KDIGO guidelines, and glomerular hyperfiltration (GHF) was defined as 95th percentile, according to the gender and age decade., Results: In obese subjects, prevalence of CKD was significantly higher with CKD EPI than with CKD DBi and CKD Mi equations (9.5%, 6.1%, 5.3%, respectively; p < 0.001), while prevalence of GHF was significantly lower (3.8%, 12.3%, 12.8%, respectively; p < 0.001). Opposite results were observed in subjects with a body mass index <25 kg/m2 for CKD (5%, 7.1%, 7.2%; p = 0.07) and GHF prevalence (6.1%, 1%, 0.6%; p < 0.001)., Discussion/conclusions: The prevalence of CKD is overestimated, and the prevalence of GHF is underestimated in obese subjects using the CKD EPI equation, i.e., the CKD EPI equation is unreliable in one-third of the population. De-indexed equations should be recommended instead of the CKD EPI equation in epidemiological studies until direct measurement of the glomerular filtration rate becomes more available., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Introduction: The impact of sexuality and quality of life (QOL) is one of the main concerns of IBD. Despite the obvious relevance of this problem, knowledge of the extent of sexual dysfunction (SD) in IBD is limited. Aim of this study was to assess the prevalence of SD and erectile dysfunction (ED), QOL their predictors, and their age-related dynamic in IBD patients., Methods: In this cross-sectional study, 202 IBD patients [122 male, 80 female, 133 Crohn's disease (CD), 69 ulcerative colitis (UC)] fulfilled International Index of Erectile Function (IIEF) or Female Sexual Functioning Index (FSFI). QOL was assessed using IBDQ-32 through bowel, systemic, emotional and social domains., Results: Prevalence of SD in men was 18%, ED 30.3% and SD in women 75%. Low QOL was present in 34.6% without gender difference (P = .253). In men, SD and ED were highest among 21-30 years and raising after 51 years of age. In women, SD was constantly highly prevalent, showing no decline over time. In multivariate analysis significant predictors of SD in men were CD phenotype, disease duration and emotional domain of IBDQ, of ED depression, emotional and bowel domain of IBDQ, and of SD in women emotional IBDQ domain., Conclusion: Quality of sex life is a serious concern among IBD patients and is age related. Components that play a role in sexual functioning in IBD require more clarification and further development of screening and treatment guidelines for SD to provide better care in the IBD population., (© 2021 John Wiley & Sons Ltd.)

Background & Aims: The Lémann Index is a tool measuring cumulative structural bowel damage in Crohn's disease (CD). We reported on its validation and updating., Methods: This was an international, multicenter, prospective, cross-sectional observational study. At each center, 10 inclusions, stratified by CD duration and location, were planned. For each patient, the digestive tract was divided into 4 organs, upper tract, small bowel, colon/rectum, anus, and subsequently into segments, explored systematically by magnetic resonance imaging and by endoscopies in relation to disease location. For each segment, investigators retrieved information on previous surgical procedures, identified predefined strictures and penetrating lesions of maximal severity (grades 1-3) at each organ investigational method (gastroenterologist and radiologist for magnetic resonance imaging), provided segmental damage evaluation ranging from 0.0 to 10.0 (complete resection). Organ resection-free cumulative damage evaluation was then calculated from the sum of segmental damages. Then investigators provided a 0-10 global damage evaluation from the 4-organ standardized cumulative damage evaluations. Simple linear regressions of investigator damage evaluations on their corresponding Lémann Index were studied, as well as calibration plots. Finally, updated Lémann Index was derived through multiple linear mixed models applied to combined development and validation samples., Results: In 15 centers, 134 patients were included. Correlation coefficients between investigator damage evaluations and Lémann Indexes were >0.80. When analyzing data in 272 patients from both samples and 27 centers, the unbiased correlation estimates were 0.89, 0,97, 0,94, 0.81, and 0.91 for the 4 organs and globally, and stable when applied to one sample or the other., Conclusions: The updated Lémann Index is a well-established index to assess cumulative bowel damage in CD that can be used in epidemiological studies and disease modification trials., (Copyright © 2021. Published by Elsevier Inc.)

Background: Multiple studies have described the effectiveness of ustekinumab (UST) and vedolizumab (VDZ) in patients with Crohn's disease (CD) failing anti- Tumor necrosis factors (TNFs); however, the effectiveness of VDZ or UST as a third-class biologic has not yet been described., Aims and Methods: In this retrospective multicenter cohort study, we aimed to investigate the effectiveness of VDZ and UST as a third-class biologic in patients with CD., Results: Two-hundred and four patients were included; 156/204 (76%) patients received VDZ as a second- and UST as a third-class therapy (group A); the remaining 48/204 (24%) patients received UST as a second- and VDZ as a third-class therapy (group B). At week 16-22, 87/156 (55.5%) patients and 27/48 (56.2%) in groups A and B, respectively, responded to treatment ( p = 0.9); 41/156 (26.2%) and 15/48 (31.2%) were in clinical remission ( p = 0.5). At week 52; 89/103 (86%) patients and 25/29 (86.2%) of the patients with available data had responded to third-class treatment in groups A and B, respectively ( p = 0.9); 31/103 (30%) and 47/29 (24.1%) were in clinical remission ( p = 0.5)., Conclusion: Third-class biological therapy was effective in more than half of the patients with CD. No differences in effectiveness were detected between the use of VDZ and UST as a third-class agent.

Background: We aimed to determine if there was a higher incidence of small intestinal bacterial overgrowth (SIBO) in non-alcoholic fatty liver disease (NAFLD) than in patients without NAFLD. Moreover, we assessed whether patients with significant fibrosis (SF) had a higher incidence of SIBO compared with patients with non-significant or no liver fibrosis., Methods: NAFLD was diagnosed in 117 patients by using Fibroscan with a controlled attenuation parameter (CAP) as well as liver biopsy (LB). SIBO was defined by esophagogastroduodenoscopy with an aspiration of the descending duodenum., Results: Patients with non-alcoholic steatohepatitis (NASH) and those with SF on LB had a significantly higher incidence of SIBO than patients without NASH and those without SF, respectively (P < .05). According to histological characteristics, there was a higher proportion of patients in the SIBO group with higher steatosis and fibrosis grade, lobular and portal inflammation, and ballooning grade (P < .001). In multivariate analysis, significant predictors associated with SF and NASH were type 2 diabetes mellitus (T2DM) and SIBO. Moreover, in multivariate analysis, significant predictors that were independently associated with SIBO were T2DM, fibrosis stage and ballooning grade (OR 8.80 (2.07-37.37), 2.50 (1.16-5.37) and 27.6 (6.41-119), respectively). The most commonly isolated were gram-negative bacteria, predominantly Escherichia coli and Klebsiella pneumoniae., Conclusion: In this relatively large population of patients, we used a gold standard for both SIBO (quantitative culture of duodenum's descending part aspirate) and NAFLD (LB), and we demonstrated that NASH patients and those with SF had a higher incidence of SIBO. Moreover, significant predictors independently associated with SIBO were T2DM, fibrosis stage and ballooning grade. Although TE is a well-investigated method for steatosis and fibrosis detection, in our study, independent predictors of SIBO were histological characteristics of NAFLD, while elastographic parameters did not reach statistical significance., (© 2021 John Wiley & Sons Ltd.)

We evaluated the diagnostic accuracy of the controlled attenuation parameter (CAP) and liver stiffness measurements (LSM) measured with either an M or XL probe against liver biopsy (LB) in patients with non-alcoholic fatty liver disease (NAFLD). This study was a cross-sectional prospective study that included 179 NAFLD patients. With a cutoff value for CAP ≥345, we can exclude significant steatosis in 87% (79.4%-92.5%) of our population. With respect to the LSM, the highest accuracy was obtained for F ≥ F3 (area under the receiver operating characteristic curve [AUROC] = 0.98) and F = F4 (AUROC = 0.98). In a multivariable linear regression model, significant predictors influencing LSM were fibrosis stage (β = 2.6, p < 0.001) as a positive predictor and lobular inflammation (β = -0.68, p = 0.04) as a negative predictor, without significant influence after adjustment for CAP and probe type. We found that CAP is a satisfactory method for excluding advanced steatosis, while LSM is a good non-invasive marker for the exclusion of fibrosis., (Copyright © 2020 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Aim: our aim was to explore the association between life habits and the controlled attenuation parameter (CAP) and liver stiffness measurements (LSM) as the surrogate markers of liver steatosis and fibrosis in a large cohort of non-alcoholic fatty liver disease (NAFLD) patients., Methods: In this prospective, cross-sectional study we had analysed 1998 patients with diagnosed NAFLD. Sleeping duration was categorised in three groups: short (S) (<6 hours), moderate (M) (6-8 hours) and long (L) (>8 hours) sleep duration. Coffee drinking was categorized into no (0), moderate (1-2) and frequent (≥3) consumption (in cups/day). Smoking was categorised as yes versus no., Results: Frequent coffee consumers had the lowest prevalence of obesity, hypertension, dyslipidaemia and diabetes. Furthermore, coffee non-consumers had highest values of hepatic enzymes, CAP and LSM. Moderate sleep duration was associated with lower values of CAP and LSM. Coffee consumption was associated with lower CAP in all the multivariate models (CAP unadjusted and model 1, 2 and 3), with largest effect in most frequent coffee consumers (≥3, model 3). Also, most frequent coffee consumers were associated with lower LSM in unadjusted model, model 1 and 2, while this was not the case for model 3 and those who consumed 1-2 cups of coffee per day. Reduced sleeping was confirmed as risk factor for elevated CAP in most of the models (unadjusted and model 1 and 2). Also, negative association of LSM was also confirmed in unadjusted model and model 2. Patients which slept 6-8 hours per day were mostly associated with lower CAP and LSM. Smoking status was not associated with CAP or LSM values., Conclusion: Coffee consumption has beneficial effect on CAP and LSM and this effect is dose dependent since and independent of a variety of relevant confounders. We have shown that moderate sleep duration has also beneficial effect on CAP and LSM., (© 2020 John Wiley & Sons Ltd.)

Aim: The primary objective of this study was to evaluate the prevalence of increased controlled attenuation parameter (CAP) and liver stiffness measurements (LSM) as surrogate markers of liver steatosis and fibrosis in liver transplant recipient (LTR). Secondary objectives were to determine the predictors of increased CAP and LSM in population of LTR., Methods: In this prospective, cross-sectional study, we have evaluated 175 LTRs' mean age as 61 (53-65) with a functioning graft for more than one year who came for regular outpatient examinations to the Department of Gastroenterology, University Hospital (UH) Merkur, Zagreb, Croatia., Results: Of 175 analyzed LTRs, 34.28% had obesity, 64.00% had hypertension, 38.28% had diabetes, and 58.85% had hyperlipidemia. The prevalence of liver steatosis was 68.57%, while the prevalence of severe liver steatosis was 46.85%. On multivariate analysis, independent factors associated with liver steatosis were male gender, total cholesterol as positive predictor, and HDL as negative predictor, and independent factors positively associated with severe liver steatosis were higher body mass index (BMI) and higher triglyceride levels. The prevalence of moderate liver fibrosis was 54.85%, while the prevalence of advanced liver fibrosis was 24%. On multivariate analysis, independent factors positively associated with moderate fibrosis were gamma-glutamyl transferase (GGT) and CAP, while the independent factor positively associated with advanced fibrosis was GGT., Conclusion: Our study showed high prevalence of increased CAP and LSM measurements as surrogate markers of liver steatosis and fibrosis. Metabolic syndrome components were highly present and were associated with CAP and LSM values as well as in the pretransplant setting. Due to high prevalence of metabolic comorbidities and nonalcoholic fatty liver disease in LTRs and the lack of the abnormal liver test in a significant number of these patients, TE with CAP may be a reasonable initial assessment for LTRs with one or more components of the metabolic syndrome., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Ivana Mikolasevic et al.)

Aim: To evaluate the effects of vitamin D on transient elastography (TE, FibroScan) indices of liver steatosis (controlled attenuation parameter [CAP]) and fibrosis (liver stiffness measurement [LSM]) in adults with non-alcoholic fatty liver disease (NAFLD)., Patients and Methods: In this randomized (2:1), double-blind, single-centre, 12-month trial, patients with NAFLD were treated with vitamin D (1000 IU/day) (n = 201) or a matching placebo (n = 110). Two co-primary outcomes were changes in CAP and LSM after 360 days of treatment versus baseline. Two main secondary outcomes were CAP/LSM changes after 180 days of treatment., Results: Both CAP and LSM gradually decreased in vitamin D-treated patients and slightly increased in the placebo arm. Vitamin D was superior to placebo for both primary outcomes (mean differences in CAP and LSM changes (-49.5 dB/m [95% CI -59.5 to -39.4] and -0.72 kPa [95% CI -1.43 to 0.00], respectively) and both secondary outcomes (-22.1 dB/m [-32.1 to -12.1] and -0.89 kPa [-1.61 to -0.17], respectively). Of a number of exploratory outcomes (change at 12 months vs. baseline), vitamin D reduced serum uric acid (-17.9 μmol/L [-30.6 to -5.2]), gamma-glutamyltransferase (-8.9 IU/L [-15.5 to -2.3)] and fasting serum insulin levels (-5.1 pmol/L [-9.3 to -0.8]) as well as the homeostatic model assessment of insulin resistance index (-1.6 [-3.1 to -0.2]) (false discovery rate [5%]-adjusted P-values between .0572 and .0952)., Conclusion: Low-medium dose supplementation of vitamin D (1000 IU/day) over 12 months reduces TE indices of liver steatosis (CAP) and fibrosis (LSM) in NAFLD patients., (© 2020 John Wiley & Sons Ltd.)

The link between metabolic syndrome (MetS) and sarcopenia has not been extensively studied, but it is evident that they share several common features. Crucial mechanisms involved in sarcopenia-nonalcoholic fatty liver disease (NAFLD) interplay are based on effects of insulin resistance, chronic inflammation, oxidative stress, and crosstalk between organs by secretion of cytokines (hepatokines, adipokines, and myokines). Currently, published studies confirm the association of sarcopenia with the degree of NAFLD defined by liver histology. However, prospective studies that will give us information regarding the causal effect of NAFLD and sarcopenia are still needed. Furthermore, there is a need for a patient-friendly, noninvasive, low-cost method for detection of loss of skeletal muscle mass, strength, and physical performance in the context of NAFLD. Moreover, potential treatment strategies such as physical exercise and nutritional supplementation, that are usually a part of management of sarcopenia, should also be investigated in NAFLD patients, especially given the fact that for now, we do not have a good treatment option for NAFLD. Therefore, future investigations should combine studies on NAFLD and sarcopenia in terms of physical activity and nutritional interventions such as vitamin D supplementation. This review aims to report recent evidence concerning the links between sarcopenia and NAFLD and methods to assess sarcopenia., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Ivana Mikolasevic et al.)

Background: The lack of scientific evidence regarding the effectiveness of 5-aminosalicylate in patients with Crohn's disease is in sharp contrast to its widespread use in clinical practice., Aims: The aim of the study was to investigate the use of 5-aminosalicylate in patients with Crohn's disease as well as the disease course of a subgroup of patients who were treated with 5-aminosalicylate as maintenance monotherapy during the first year of disease., Methods: In a European community-based inception cohort, 488 patients with Crohn's disease were followed from the time of their diagnosis. Information on clinical data, demographics, disease activity, medical therapy and rates of surgery, cancers and deaths was collected prospectively. Patient management was left to the discretion of the treating gastroenterologists., Results: Overall, 292 (60%) patients with Crohn's disease received 5-aminosalicylate period during follow-up for a median duration of 28 months (interquartile range 6-60). Of these, 78 (16%) patients received 5-aminosalicylate monotherapy during the first year following diagnosis. Patients who received monotherapy with 5-aminosalicylate experienced a mild disease course with only nine (12%) who required hospitalization, surgery, or developed stricturing or penetrating disease, and most never needed more intensive therapy. The remaining 214 patients were treated with 5-aminosalicylate as the first maintenance drug although most eventually needed to step up to other treatments including immunomodulators (75 (35%)), biological therapy (49 (23%)) or surgery (38 (18%))., Conclusion: In this European community-based inception cohort of unselected Crohn's disease patients, 5-aminosalicylate was commonly used. A substantial group of these patients experienced a quiescent disease course without need of additional treatment during follow-up. Therefore, despite the controversy regarding the efficacy of 5-aminosalicylate in Crohn's disease, its use seems to result in a satisfying disease course for both patients and physicians.

Background: Ustekinumab is effective in Crohn's disease. However, a substantial proportion of patients will not respond or lose response to ustekinumab. The current evidence to support the effectiveness of dose-optimisation for ustekinumab nonresponse is limited., Aim: To assess the effectiveness of dose escalation of ustekinumab., Methods: This was a multicentre retrospective cohort study. We included active Crohn's disease patients who received a standard-dose intravenous induction and at least one subcutaneous ustekinumab 90 mg dose. All enrolled patients received dose escalation by either shortening the interval between the doses to every 4 or 6 weeks, intravenous reinduction or a combination of strategies. The primary outcome of the study was clinical response at week 16 after dose escalation., Results: A total of 142 patients (22 centres/14 countries) were included. The patients were dose-escalated after a median treatment duration of 30 weeks. At week 16 from escalation, 73/142 (51.4%) responded to treatment, including 55/142 (38.7%) in clinical remission. Corticosteroid-free remission was achieved in 6/34 (17.6%) patients on corticosteroids at the time of escalation; 118/142 (83%) continued treatment beyond week 16. Follow-up data beyond week 16 were available for 74/118 (62.7%) patients. On the last follow-up, 51/98 (52%) patients with available data responded to treatment, including 41/98 (42%) in clinical remission., Conclusions: Intensification of ustekinumab maintenance dosage was effective in over 50% of the patients. This strategy should be considered in patients who are nonresponsive to every 8 weeks ustekinumab maintenance dosing., (© 2020 John Wiley & Sons Ltd.)

Background: Inflammatory bowel disease (IBD) places a significant burden on health-care systems because of its chronicity and need for expensive therapies and surgery. With increasing use of biological therapies, contemporary data on IBD health-care costs are important for those responsible for allocating resources in Europe. To our knowledge, no prospective long-term analysis of the health-care costs of patients with IBD in the era of biologicals has been done in Europe. We aimed to investigate cost profiles of a pan-European, community-based inception cohort during 5 years of follow-up., Methods: The Epi-IBD cohort is a community-based, prospective inception cohort of unselected patients with IBD diagnosed in 2010 at centres in 20 European countries plus Israel. Incident patients who were diagnosed with IBD according to the Copenhagen Diagnostic Criteria between Jan 1, and Dec 31, 2010, and were aged 15 years or older the time of diagnosis were prospectively included. Data on clinical characteristics and direct costs (investigations and outpatient visits, blood tests, treatments, hospitalisations, and surgeries) were collected prospectively using electronic case-report forms. Patient-level costs incorporated procedures leading to the initial diagnosis of IBD and costs of IBD management during the 5-year follow-up period. Costs incurred by comorbidities and unrelated to IBD were excluded. We grouped direct costs into the following five categories: investigations (including outpatient visits and blood tests), conventional medical treatment, biological therapy, hospitalisation, and surgery., Findings: The study population consisted of 1289 patients with IBD, with 1073 (83%) patients from western Europe and 216 (17%) from eastern Europe. 488 (38%) patients had Crohn's disease, 717 (56%) had ulcerative colitis, and 84 (6%) had IBD unclassified. The mean cost per patient-year during follow-up for patients with IBD was €2609 (SD 7389; median €446 [IQR 164-1849]). The mean cost per patient-year during follow-up was €3542 (8058; median €717 [214-3512]) for patients with Crohn's disease, €2088 (7058; median €408 [133-1161]) for patients with ulcerative colitis, and €1609 (5010; median €415 [92-1228]) for patients with IBD unclassified (p<0·0001). Costs were highest in the first year and then decreased significantly during follow-up. Hospitalisations and diagnostic procedures accounted for more than 50% of costs during the first year. However, in subsequent years there was a steady increase in expenditure on biologicals, which accounted for 73% of costs in Crohn's disease and 48% in ulcerative colitis, in year 5. The mean annual cost per patient-year for biologicals was €866 (SD 3056). The mean yearly costs of biological therapy were higher in patients with Crohn's disease (€1782 [SD 4370]) than in patients with ulcerative colitis (€286 [1427]) or IBD unclassified (€521 [2807]; p<0·0001)., Interpretation: Overall direct expenditure on health care decreased over a 5-year follow-up period. This period was characterised by increasing expenditure on biologicals and decreasing expenditure on conventional medical treatments, hospitalisations, and surgeries. In light of the expenditures associated with biological therapy, cost-effective treatment strategies are needed to reduce the economic burden of inflammatory bowel disease., Funding: Kirsten og Freddy Johansens Fond and Nordsjællands Hospital Forskningsråd., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background & Aims: Cancer cachexia (CC) syndrome and anorexia-cachexia syndrome are common terms used to describe changes in metabolism with increased inflammatory activity and can progressively develop through various stages such as pre-cachexia; cachexia; and refractory cachexia. Therefore in year 2007 Croatian guidelines for use of eicosapentaenoic acid and megestrol acetate in cancer cachexia syndrome were published. Aim of this study was to assess the awareness and implementation of Croatian guidelines for use of eicosapentaenoic acid (EPA) and megestrol acetate (MA) into clinical practice among Croatian oncologists approximately 10 years after the publication, but also to point out the importance of adequate recognition and treatment of CC., Methods: Survey with questions was designed to assess the awareness and implementation of Croatian guidelines for use of EPA and MA into clinical practice and was distributed among all Croatian oncologists in secondary and tertiary hospital centers. Survey was conducted in January 2011 (40 months following release of the guidelines), February 2013 and June 2018, and were formed in a way of yes/no answers. Additional multiple choice questions that focus on the implementation of guidelines were added in June 2018., Results: A total of 128 oncologists completed a questionnaire. There was no statistically significant difference in follow up period (2011-2018) of percentage of oncologists that are familiar with Croatian guidelines for use of EPA and MA in CC, percentage of oncologists in which Croatian national guidelines changed their approach in treating patients with CC syndrome and proportion of oncologists that are using MA, enteral nutrition formulas with EPA or their combination. Most of the oncologists 38% (N = 44) are using >2.2 g of EPA per day. Nutritional support is prescribed in 25-50% of patients by 42% (N = 48) of oncologists and most of the oncologists (35%, N = 41) start with nutritional support when a body mass loss is >5%. Oncologists mostly recommend patients to use nutritional support during 1 year or more (43%, N = 49) or two months to 1 year (42%, N = 48). Compliance of patients with malignant diseases for using nutritional support was mostly evaluated as medium (69%, N = 60)., Conclusions: Results have shown that majority of oncologists who filled the questionnaire believe that the Croatian national guidelines for use of EPA and MA in CC syndrome changed their approach in treating patients with CC, but also that there are several targeted issues that can be significantly improved. The awareness of and adherence to national guidelines was maintained at high level even 11 years after the guidelines were published., (Copyright © 2019 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)