Co-Administration of Proton Pump Inhibitors May Negatively Affect the Outcome in Inflammatory Bowel Disease Treated with Vedolizumab.

Concomitant medications may alter the effect of biological therapy in inflammatory bowel disease. The aim was to investigate the effect of proton pump inhibitors on remission rates in patients with inflammatory bowel disease treated with the gut-selective vedolizumab. Patients from the Hungarian nationwide, multicenter vedolizumab cohort were selected for post hoc analysis. Primary outcomes were the assessment of clinical response and endoscopic and clinical remission at weeks 14 and 54. Secondary outcomes were the evaluation of the combined effect of concomitant steroid therapy and other factors, such as smoking, on remission. A total of 108 patients were identified with proton pump inhibitor data from 240 patients in the original cohort. Patients on steroids without proton pump inhibitors were more likely to have a clinical response at week 14 than patients on concomitant PPI (95% vs. 67%, p = 0.005). Non-smokers with IBD treated with VDZ were more likely to develop a clinical response at week 14 than smokers, particularly those not receiving PPI compared with patients on co-administered PPI therapy (81% vs. 53%, p = 0.041, and 92% vs. 74%, p = 0.029, respectively). We found that the use of PPIs in patients treated with VDZ may impair the achievement of response in certain subgroups. Unnecessary PPI prescriptions should be avoided.

Psychological characteristics of patients with inflammatory bowel disease during the first wave of COVID-19.

Introduction: Inflammatory bowel diseases (Crohn's disease (CD) and ulcerative colitis (UC)) are chronic, immune-mediated diseases with unclear aetiology, characterized by relapsing inflammation of the gastrointestinal tract. These conditions significantly impair patients' physical and mental condition and quality of life. Aim: To investigate the impact of the current pandemic situation on inflammatory bowel disease (IBD) patients' psychological status and to determine factors that mediate the level of depression, anxiety, and health-related quality of life. Material and methods: This was a multicentre, observational, cross-sectional, questionnaire-based study. A total of 206 participants (male: 34%) were involved. The online survey consisted of 8 different psychological measures (such as depression, anxiety, coronavirus distress, health-related quality of life, etc.) and other therapy-specific and sociodemographic factors. Results: 28.2% of respondents showed depressive symptoms and 11.2% indicated moderate to severe anxiety. Also, 27.7% revealed mild, moderate, or severe distress regarding the coronavirus situation. According to regression analysis, anxiety and coronavirus distress are mostly influenced by psychological factors. In contrast, the changes in quality of life and depression can be explained by disease-specific and psychological factors as well. Conclusions: Patients need more attention during this period to help them cope with psychological factors and prevent their IBD from becoming worse.

Real-Life Efficacy of Tofacitinib in Various Situations in Ulcerative Colitis: A Retrospective Worldwide Multicenter Collaborative Study.

BACKGROUND AND AIMS: Tofacitinib (TFB) appears to be effective in the treatment of ulcerative colitis (UC); however, available real-world studies are limited by cohort size. TFB could be an option in the treatment of acute severe ulcerative colitis (ASUC). We aimed to investigate efficacy and safety of TFB in moderate-to-severe colitis and ASUC. METHODS: This retrospective, international cohort study enrolling UC patients with ≥6-week follow-up period was conducted from February 1 to July 31, 2022. Indications were categorized as ASUC and chronic activity (CA). Baseline demographic and clinical data were obtained. Steroid-free remission (SFR), colectomy, and safety data were analyzed. RESULTS: A total of 391 UC patients (median age 38 [interquartile range, 28-47] years; follow-up period 26 [interquartile range, 14-52] weeks) were included. A total of 27.1% received TFB in ASUC. SFR rates were 23.7% (ASUC: 26.0%, CA: 22.8%) at week 12 and 41.1% (ASUC: 34.2%, CA: 43.5%) at week 52. The baseline partial Mayo score (odds ratio [OR], 0.850; P = .006) was negatively associated with week 12 SFR, while biologic-naïve patients (OR, 2.078; P = .04) more likely achieved week 52 SFR. The colectomy rate at week 52 was higher in ASUC group (17.6% vs 5.7%; P < .001) and decreased with age (OR, 0.94; P = .013). A total of 67 adverse events were reported, and 17.9% resulted in cessation of TFB. One case of thromboembolic event was reported. CONCLUSIONS: TFB is effective in both studied indications. TFB treatment resulted in high rates of SFR in the short and long terms. Higher baseline disease activity and previous biological therapies decreased efficacy. No new adverse event signals were found.

Self-reported efficacy and safety of infliximab and adalimumab biosimilars after non-medical switch in patients with inflammatory bowel disease: results of a multicenter survey.

BACKGROUND: Few data are available on subjective disease control and perception of adverse events (AEs) during switching from original anti-TNF agents to biosimilars. RESEARCH DESIGN AND METHODS: Hungarian patients with inflammatory bowel disease were interviewed after a mandatory non-medical switch from an infliximab (IFX) originator to a biosimilar GP1111 or from an adalimumab (ADA) originator to a biosimilar GP2017. Drug choice was based on patient's and physician's decision. Subjective efficacy was measured using a 10-point scale, and AEs were assessed. Difference in efficacy before and after the switch was compared within and between the drugs. RESULTS: Seventy-three ADA and 106 IFX switching patients were interviewed. Subjective efficacy of IFX biosimilar was rated lower compared to IFX originator (8.72 ± 1.68 vs. 7.77 ± 2.34; p = 0.001). The ADA biosimilar was rated higher than its originator (9.02 ± 1.61 vs. 8.42 ± 1.93; p = 0.017). Patients receiving ADA biosimilar were more satisfied with the new treatment compared to IFX (p = 0.032). The incidence of new AEs was 85% in the ADA and 55% in the IFX group (1.79 vs. 0.93 AEs per patient, respectively, p < 0.001). CONCLUSION: Subjective efficacy of switching to a biosimilar was proven in case of ADA, while reduced efficacy was experienced with IFX biosimilar. Perception of AEs was high and varied between biosimilars.

Hungarian Linguistic, Cross-Cultural and Age Adaptation of Transition Specific Questionnaires in Patients with Inflammatory Bowel Disease.

Objective: In the TRANS-IBD clinical trial, the outcomes are measured with selected validated questionnaires. Cross-cultural and age adaptations of the Self-Efficacy Scale for adolescents and young adults (IBD-SES), the Transition Readiness Assessment Questionnaire (TRAQ), and the Self-Management and Transition Readiness Questionnaire (STARx) were performed. Methods: Linguistic and cultural adaptation was carried out with the usage of reliability coefficients (Cronbach's α coefficients, Spearman's rank correlation), and with confirmatory factor analysis (CFA; root Mean Square Error of Approximation [RMSEA], Comparative Fit Index [CFI], and Tucker-Lewis Index [TLI]). Results: 112 adolescents participated in the study (45.5% male, mean age 17 ± 1.98 years). CFA was acceptable in the IBD-SES and the TRAQ. Internal consistency was acceptable in IBD-SES and good in TRAQ (0.729; 0.865, respectively). Test-retest reliability was good in IBD-SES, but below the acceptable threshold in TRAQ (ρ = 0.819; ρ = 0.034). In STARx tools, RMSEA showed poor fit values, CFI and TLI were below acceptable fit values, and internal consistency was not satisfied (0.415; 0.693, respectively), while test-retest reliabilities were acceptable (ρ = 0.787; ρ = 0.788, respectively). Conclusions: Cross-cultural, age-specific adaptation was successfully completed with IBD-SES and TRAQ. Those are comparable to the original validated versions. The adaption of the STARx tools was not successful.

Suprapapillary Biliary Stents Have Longer Patency Times than Transpapillary Stents-A Systematic Review and Meta-Analysis.

BACKGROUND AND STUDY AIMS: Endoscopic biliary stent placement is a minimally invasive intervention for patients with biliary strictures. Stent patency and function time are crucial factors. Suprapapillary versus transpapillary stent positioning may contribute to stent function time, so a meta-analysis was performed in this comparison. METHODS: A comprehensive literature search was conducted in the CENTRAL, Embase, and MEDLINE databases to find data on suprapapillary stent placement compared to the transpapillary method via endoscopic retrograde cholangiopancreatography in cases of biliary stenosis of any etiology and any stent type until December 2020. We carried out a meta-analysis focusing on the following outcomes: stent patency, stent migration, rate of cholangitis and pancreatitis, and other reported complications. RESULTS: Three prospective and ten retrospective studies involving 1028 patients were included. Suprapapillary stent placement appeared to be superior to transpapillary stent positioning in patency (weighted mean difference = 50.23 days, 95% CI: 8.56, 91.98; p = 0.0.018). In a subgroup analysis of malignant indications, suprapapillary positioning showed a lower rate of cholangitis (OR: 0.34, 95% CI: 0.13, 0.93; p = 0.036). Another subgroup analysis investigating metal stents in a suprapapillary position resulted in a lower rate of pancreatitis (OR: 0.16, 95% CI: 0.03, 0.95; p = 0.043) compared to transpapillary stent placement. There was no difference in stent migration rates between the two groups (OR: 0.67, 95% CI: 0.17, 2.72; p = 0.577). CONCLUSIONS: Based on our results, suprapapillary biliary stenting has longer stent patency. Moreover, the stent migration rate did not differ between the suprapapillary and transpapillary groups.

Conception and reality: Outcome of SARS-CoV-2 infection and vaccination among Hungarian IBD patients on biologic treatments.

Introduction: Inflammatory bowel disease potentially elevates the risk of infections, independently from age, while the disease activity and medical treatment(s) can also increase the risks. Nevertheless, it is necessary to clarify these preconceptions as well during the COVID-19 pandemic. Methods: An observational, questionnaire based study was conducted in Hungary between February and August 2021. 2 questionnaires were completed. The first questionnaire surveyed the impact of the pandemic on patients with biologic treatments and assessed the severity and outcome of the infection, whereas the second one assessed vaccination rate and adverse events. Results: 472 patients participated in the study. 16.9 % of them acquired the infection and 6.3 % needed hospitalization. None of them required ICU care. Male sex elevated the risk of infection (p = 0.008), while glove (p = 0.02) and mask wearing (p = 0.005) was the most effective prevention strategy. Nevertheless, abstaining from community visits or workplace did not have an impact on the infection rate. Smoking, age, and disease type did not elevate the risk. UC patients had poorer condition during the infection (p = 0.003); furthermore, the disease activity could potentially worsen the course of infection (p = 0.072). The different biological treatments were equally safe; no difference was observed in the infection rate, course of COVID-19. Azathioprine and corticosteroids did not elevate the infection rate. 28 patients (35.0 %) suspended the ongoing biologic treatment, but it had no impact on the disease course. However, it resulted in changing the current treatment (p = 0.004). 9.8 % of the respondents were sceptic about being vaccinated, and 90 % got vaccinated. In one case, a serious flare-up occurred. Discussion: Most patients acquired the infection at workplace. Biologic therapies had no effect on the COVID-19 infection, whereas male sex, an active disease, and UC could be larger threat than treatments. Vaccination was proved to be safe, and patient education is important to achieve mass vaccination of the population.

Inflammatory bowel disease does not alter the clinical features and the management of acute pancreatitis: A prospective, multicentre, exact-matched cohort analysis.

OBJECTIVE AND AIMS: Acute pancreatitis in inflammatory bowel disease occurs mainly as an extraintestinal manifestation or a side effect of medications. We aimed to investigate the prognostic factors and severity indicators of acute pancreatitis and the treatment of patients with both diseases. DESIGN: We performed a matched case-control registry analysis of a multicentre, prospective, international acute pancreatitis registry. Patients with both diseases were matched to patients with acute pancreatitis only in a 1:3 ratio by age and gender. Subgroup analyses were also carried out based on disease type, activity, and treatment of inflammatory bowel disease. RESULTS: No difference in prognostic factors (laboratory parameters, bedside index of severity in acute pancreatitis, imaging results) and outcomes of acute pancreatitis (length of hospitalization, severity, and local or systemic complications) were detected between groups. Significantly lower analgesic use was observed in the inflammatory bowel disease population. Antibiotic use during acute pancreatitis was significantly more common in the immunosuppressed group than in the non-immunosuppressed group (p = 0.017). However, none of the prognostic parameters or the severity indicators showed a significant difference between any subgroup of patients with inflammatory bowel disease. CONCLUSION: No significant differences in the prognosis and severity of acute pancreatitis could be detected between patients with both diseases and with pancreatitis only. The need for different acute pancreatitis management is not justified in the coexistence of inflammatory bowel disease, and antibiotic overuse should be avoided.

Hungarian Linguistic, Cross-Cultural, and Age Adaptation of the Patient Satisfaction with Health Care in Inflammatory Bowel Disease Questionnaire (CACHE) and the Medication Adherence Report Scale (MARS).

BACKGROUND: The TRANS-IBD study examines the superiority of joint transition visits, with drug adherence and patient satisfaction among the outcome measures. Our aim was a cross-cultural, age- and disease-specific adaptation of the 'Medication Adherence Rating Scale' (MARS) and 'Patient satisfaction with health care in inflammatory bowel disease questionnaire' (CACHE) questionnaires in patients with inflammatory bowel disease (IBD). METHODS: Linguistic and cultural adaptation using test and re-test procedures were performed. Internal consistency with Cronbach's α coefficients, confirmatory factor analyses with root Mean Square Error of Approximation (RMSEA), Comparative Fit Index (CFI), and Tucker-Lewis Index (TLI) were determined. RESULTS: A total of 122 adolescents and 164 adults completed the questionnaires (47.5% male, mean age 17 ± 1; and 29.3% male, mean age 38 ± 11, respectively). In the MARS questionnaire, Cronbach's α scores were found good in adolescents (0.864) and acceptable in adults (0.790), while in the CACHE questionnaire, scores were rated as excellent in both populations (0.906 and 0.945, respectively). The test-retest reliabilities were satisfactory in both groups (MARS questionnaire: r = 0.814 and r = 0.780, CACHE questionnaire: r = 0.892 and r = 0.898, respectively). RMSEA showed poor fit values in the MARS questionnaire and reasonable fit values in the CAHCE questionnaire, CFI and TLI had statistically acceptable results. CONCLUSION: Age-and disease-specific Hungarian versions of the questionnaires were developed, which are appropriate tools for TRANS-IBD RCT and daily IBD care.

Fecal calprotectin levels in pediatric cow's milk protein allergy.

Introduction: The most prevalent food allergy in younger children is cow's milk protein allergy (CMPA), a hypersensitivity reaction to cow's milk protein and its most common clinical manifestation is allergic colitis. The goal of our recent study was to assess somatic symptoms of CMPA and to prospectively observe the effects of a dairy elimination diet using objective parameters and questionnaires. Methods: The County Hospital in Szekszárd, Hungary, investigated children aged 1 to 18 who had clinical signs that might indicate CMPA. Stool samples were taken and analyzed using a fecal calprotectin (FC) rapid test (Quantum Blue fCAL, Bühlmann Laboratories, Switzerland) at the time of the diagnosis and following 3 months of an elimination diet. At the baseline visit as well as the first and second follow-up, questionnaires were filled out. Patients were divided into two subgroups according to dietary guidelines based on the results of the questionnaires. Results: A total of 47 patients participated in the study [42.55% female, mean age: 7.36 (SD 4.22) years]. There was no significant difference in FC levels between baseline and after 3-month elimination diet [73.98 (71.12) µg/g and 68.11 (74.4) µg/g, respectively, p = 0.331]. After three months, there was a significant decrease in FC levels among patients who adhered to the strict diet [84.06 (79.48) µg/g and 41.11 (34.24) µg/g, respectively, p = 0.001]. Conclusion: The findings of our study suggest that FC can be an objective marker in confirming the diagnosis of CMPA. Significant improvement in clinical symptoms and in FC levels can only be expected after a strictly followed elimination diet.

EASY-APP: An artificial intelligence model and application for early and easy prediction of severity in acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a potentially severe or even fatal inflammation of the pancreas. Early identification of patients at high risk for developing a severe course of the disease is crucial for preventing organ failure and death. Most of the former predictive scores require many parameters or at least 24 h to predict the severity; therefore, the early therapeutic window is often missed. METHODS: The early achievable severity index (EASY) is a multicentre, multinational, prospective and observational study (ISRCTN10525246). The predictions were made using machine learning models. We used the scikit-learn, xgboost and catboost Python packages for modelling. We evaluated our models using fourfold cross-validation, and the receiver operating characteristic (ROC) curve, the area under the ROC curve (AUC), and accuracy metrics were calculated on the union of the test sets of the cross-validation. The most critical factors and their contribution to the prediction were identified using a modern tool of explainable artificial intelligence called SHapley Additive exPlanations (SHAP). RESULTS: The prediction model was based on an international cohort of 1184 patients and a validation cohort of 3543 patients. The best performing model was an XGBoost classifier with an average AUC score of 0.81 ± 0.033 and an accuracy of 89.1%, and the model improved with experience. The six most influential features were the respiratory rate, body temperature, abdominal muscular reflex, gender, age and glucose level. Using the XGBoost machine learning algorithm for prediction, the SHAP values for the explanation and the bootstrapping method to estimate confidence, we developed a free and easy-to-use web application in the Streamlit Python-based framework (http://easy-app.org/). CONCLUSIONS: The EASY prediction score is a practical tool for identifying patients at high risk for severe AP within hours of hospital admission. The web application is available for clinicians and contributes to the improvement of the model.

Preoperative Serum Carbohydrate Antigen 19-9 Levels Cannot Predict the Surgical Resectability of Pancreatic Cancer: A Meta-Analysis.

Background and Aims: Pancreatic ductal adenocarcinoma has one of the worst prognosis of all malignancies. This investigated the relationship between the preoperative serum carbohydrate antigen 19-9 and surgical resectability. Methods: A systematic search was performed in three databases (MEDLINE, EMBASE, and Web of Science) to compare the surgical resectability of pancreatic ductal adenocarcinoma in patients with high and low preoperative serum carbohydrate antigen 19-9 values. The receiving operating characteristic curves were constructed and the weighted mean differences for preoperative serum carbohydrate antigen 19-9 levels of resectable and unresectable groups of patients were calculated. The PROSPERO registration number is CRD42019132522. Results: Results showed that there was a significant difference in resectability between the low and high carbohydrate antigen 19-9 groups. Six out of the eight studies utilised receiver operating characteristic curves in order to find the cut-off preoperative carbohydrate antigen 19-9 levels marking unresectability. The overall result from the pooled area under curve values from the receiver operating characteristic curves was 0.794 (CI: 0.694-0.893), showing that the preoperative carbohydrate antigen 19-9 level is a "fair" marker of resectability. The result of the pooled weighted mean differences was 964 U/ml (p < 0.001) showing that there is a significant carbohydrate antigen 19-9 difference between the resectable and unresectable groups. Based on the results of the I-squared test, the result was 87.4%, accounting for "considerable" heterogeneity within the population. Conclusion: Carbohydrate antigen 19-9 is not a reliable marker of unresectability, it should not be used on its own in surgical decision-making.

In-Hospital Patient Education Markedly Reduces Alcohol Consumption after Alcohol-Induced Acute Pancreatitis.

Although excessive alcohol consumption is by far the most frequent cause of recurrent acute pancreatitis (AP) cases, specific therapy is still not well established to prevent recurrence. Generally, psychological therapy (e.g., brief intervention (BI)) is the cornerstone of cessation programs; however, it is not yet widely used in everyday practice. We conducted a post-hoc analysis of a prospectively collected database. Patients suffering from alcohol-induced AP between 2016 and 2021 received 30 min BI by a physician. Patient-reported alcohol consumption, serum gamma-glutamyl-transferase (GGT) level, and mean corpuscular volume (MCV) of red blood cells were collected on admission and at the 1-month follow-up visit to monitor patients' drinking habits. Ninety-nine patients with alcohol-induced AP were enrolled in the study (mean age: 50 ± 11, 89% male). A significant decrease was detected both in mean GGT value (294 ± 251 U/L vs. 103 ± 113 U/L, p < 0.001) and in MCV level (93.7 ± 5.3 U/L vs. 92.1 ± 5.1 U/L, p < 0.001) in patients with elevated on-admission GGT levels. Notably, 79% of the patients (78/99) reported alcohol abstinence at the 1-month control visit. Brief intervention is an effective tool to reduce alcohol consumption and to prevent recurrent AP. Longitudinal randomized clinical studies are needed to identify the adequate structure and frequency of BIs in alcohol-induced AP.

Immune response to influenza and pneumococcal vaccines in adults with inflammatory bowel disease: A systematic review and meta-analysis of 1429 patients.

BACKGROUND: Patients with inflammatory bowel disease (IBD) have a high risk for infection. Pneumonia related to influenza and pneumococcal infection is one of the most common infection-related complications in IBD. AIMS: To evaluate the immunogenicity of pneumococcal and influenza vaccination in patients with IBD receiving different treatments. METHODS: We searched four databases for studies evaluating seroprotection and seroconversion rates after influenza or pneumococcal vaccination in IBD on 20th October 2020. In the meta-analysis, odds ratios (OR) were calculated with 95% confidence intervals (CI). RESULTS: We included twelve studies (1429 patients with IBD) in this meta-analysis. The seroconversion rate after pneumococcal vaccination and the seroprotection rate after influenza vaccination were not significantly lower in patients receiving conventional immunosuppressive treatment compared to the non-immunosuppressed patients. Meanwhile, the seroconversion rate following pneumococcal vaccine was significantly lower in patients with anti-TNF mono- or combination therapy (OR = 0.28, CI: 0.15-0.53, and OR = 0.27, CI: 0.15-0.49, respectively). In the analysis of patients with IBD on conventional immunosuppressive monotherapy versus anti-TNF therapy, the seroprotection rate after influenza immunization did not differ between patients receiving either anti-TNF mono-or combination therapy (OR = 1.45, CI: 0.62-3.38 and OR = 0.91, CI: 0.37-2.22, respectively). CONCLUSION: Our data suggest that the immunization against Pneumococcus and influenza is safe and immunogenic despite immunosuppression.

Ustekinumab is associated with superior treatment persistence but not with higher remission rates versus vedolizumab in patients with refractory Crohn's disease: results from a multicentre cohort study.

Background: Treatment with antitumor necrosis factor alpha (anti-TNF-α) is safe and effective as first-line therapy; however, its efficacy is limited due to primary nonresponse (PNR) and secondary loss of response (LOR), resulting in treatment discontinuation in approximately 40%-50% of cases. Vedolizumab (VDZ) and ustekinumab (UST) therapies could be good alternatives in patient with anti-TNF failure; however, no head-to-head randomized comparison of these drugs as second- or third-line treatments has been made. Objectives: This study aimed to assess the treatment persistence and comparative effectiveness of UST and VDZ in patients with refractory Crohn's disease (CD). Design: In this nationwide retrospective study, patients with CD on UST or VDZ maintenance therapy were enrolled. Clinical data at baseline, after induction, and at week 52 were obtained. Methods: Clinical and biochemical activities as well as corticosteroid-free remission (SFR) rates were assessed, while concomitant medications, comorbidities, hospitalizations, and surgeries were recorded during the follow-up to detect any predictors. Results: A total of 161 UST- and 65 VDZ-treated patients completed the follow-up. No significant difference in clinical or biochemical remission rates was observed after induction between the two treatment groups; however, clinical remission rate at week 52 was higher in UST group. UST showed superior drug persistence than VDZ (86.5%, 57.9%, p < 0.0001). The drug type was predictive of clinical SFR at week 52 [p = 0.011, odds ratio (OR) = 2.39 with UST]. Drug failure rates were higher for VDZ than those for UST (PNR rates: 21.54% and 4.97%, respectively, p < 0.001, OR = 8.267, p = 0.001). LOR and escalations were more common during UST treatment (61.5% versus 36.9%, p < 0.001; 64.2% versus 23.1%, p < 0.001). Hospital and surgical admission rates did not differ significantly. Only one adverse event occurred with VDZ at week 20, which led to drug cessation. Conclusions: VDZ and UST were safe and effective for treating patients with CD in whom anti-TNF therapy failed. UST showed superior drug persistence than VDZ, but dose escalation was more frequent. Biologicals used in lower treatment lines resulted in better drug persistence.

Clinical efficacy, drug sustainability and serum drug levels in Crohn's disease patients treated with ustekinumab - A prospective, multicenter cohort from Hungary.

INTRODUCTION: Although efficacy of ustekinumab (UST) has been demonstrated through randomized trials, data from real-life prospective cohorts are still limited. Our aim was to evaluate clinical efficacy, drug sustainability, dose intensification and results from therapeutic drug monitoring in UST treated patients with Crohn's disease (CD) using a prospective, nationwide, multicenter cohort. METHODS: Patients from 10 Inflammatory Bowel Disease centers were enrolled between 2019 January and 2020 May. Patient demographics, disease phenotype, treatment history, clinical disease activity (Crohn's Disease Activity Index(CDAI), Harvey Bradshaw Index(HBI)), biomarkers, and serum drug levels were obtained. Evaluations were performed at week8 (post-induction), w16-20, w32-36, and w52-56 follow-up visits. RESULTS: A total of 142 patients were included [57.4% female; complex disease behavior (B2/B3):48%, previous anti-TNF exposition:97%]. Clinical response and remission rates after induction(w8) were 78.1% and 57.7% using CDAI, and 82.5% and 51.8% based on HBI scores. The one-year clinical remission rate was 58%/57.3%(CDAI/HBI). Composite clinical and biomarker remission (CDAI<150 and C-reactive protein<10 mg/L) rates were 35.4%; 33.3%; 38.6% and 36.6% at w8/w16-20/w32-36 and w52-56. Drug sustainability was 81.9%(standard deviation(SD): 3.4) at 1 year(1y). Probability of dose intensification was high and introduced early, 42.2%(SD:4.2) at ~w32 and 51.9%(SD:4.4%) at 1y. CONCLUSION: Ustekinumab showed favorable drug sustainability and clinical efficacy in a patient population with severe disease phenotype and previous anti-tumor necrosis factor (anti-TNF) failure, however frequent dose intensification was required.

Hypoalbuminemia affects one third of acute pancreatitis patients and is independently associated with severity and mortality.

The incidence and medical costs of acute pancreatitis (AP) are on the rise, and severe cases still have a 30% mortality rate. We aimed to evaluate hypoalbuminemia as a risk factor and the prognostic value of human serum albumin in AP. Data from 2461 patients were extracted from the international, prospective, multicentre AP registry operated by the Hungarian Pancreatic Study Group. Data from patients with albumin measurement in the first 48 h (n = 1149) and anytime during hospitalization (n = 1272) were analysed. Multivariate binary logistic regression and Receiver Operator Characteristic curve analysis were used. The prevalence of hypoalbuminemia (< 35 g/L) was 19% on admission and 35.7% during hospitalization. Hypoalbuminemia dose-dependently increased the risk of severity, mortality, local complications and organ failure and is associated with longer hospital stay. The predictive value of hypoalbuminemia on admission was poor for severity and mortality. Severe hypoalbuminemia (< 25 g/L) represented an independent risk factor for severity (OR 48.761; CI 25.276-98.908) and mortality (OR 16.83; CI 8.32-35.13). Albumin loss during AP was strongly associated with severity (p < 0.001) and mortality (p = 0.002). Hypoalbuminemia represents an independent risk factor for severity and mortality in AP, and it shows a dose-dependent relationship with local complications, organ failure and length of stay.

Diabetes Mellitus Increases the Risk of Hepatocellular Carcinoma After Direct-Acting Antiviral Therapy: Systematic Review and Meta-Analysis.

Background: Hepatitis C virus (HCV)-infected patients treated with direct-acting antivirals (DAAs) are still at risk of developing hepatocellular carcinoma (HCC) after sustained virologic response (SVR). This study aimed to investigate the role of diabetes mellitus (DM) as a potential predictive risk factor in developing de novo HCC in HCV-infected patients after DAA treatment. Methods: This study was registered on PROSPERO under registration number CRD42021230457. We performed a systematic search in four medical databases from inception through November 3rd, 2020. Studies were eligible if they reported on HCV-infected patients treated with DAAs and compared the frequency of de novo HCC in patients with and without DM. We calculated pooled odds ratios, unadjusted (UHR), and adjusted hazard ratios (AHR) with 95% confidence intervals (CIs) in meta-analysis. Results: We included 30 articles in our systematic review and meta-analysis. DM proved to be a significant risk factor of HCC in DAA-treated HCV patients in unadjusted (UHR = 1.44, CI: 1.15-1.79) and adjusted analyses (AHR = 1.31, CI: 1.06-1.62). In the group of patients achieving SVR after DAA therapy, DM increased the risk of HCC in unadjusted (UHR = 1.3, CI: 1.09-1.51) analysis; however, in adjusted results, the risk was non-significant (AHR = 1.07, CI: 0.89-1.28). In patients with advanced liver fibrosis, DM was a risk factor for HCC in adjusted (AHR = 1.36, CI: 1.03-1.8), but not in unadjusted analysis (UHR = 1.11, CI: 0.8-1.42). Conclusions: DM is an independent risk factor of de novo HCC after DAA treatment in HCV-infected patients. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=230457, identifier: CRD42021230457.