The Natural History of Patients With Pre-Existing and De Novo Inflammatory Bowel Disease After Solid Organ Transplantation: EITOS Study of GETECCU.

BACKGROUND: Limited data are available on the outcome of inflammatory bowel disease (IBD) in patients with solid organ transplantation (SOT). We describe the natural history of pre-existing IBD and de novo IBD after SOT. METHODS: This was a retrospective, multicenter study that included patients with pre-existing IBD at the time of SOT and patients with de novo IBD after SOT. The primary outcome was IBD progression, defined by escalation of medical treatment, surgical therapy, or hospitalization due to refractory IBD. Risk factors were identified using multivariate Cox proportional hazard analysis. RESULTS: A total of 177 patients (106 pre-existing IBD and 71 de novo IBD) were included. Most patients with pre-existing IBD (92.5%) were in remission before SOT. During follow-up, 32% of patients with pre-existing IBD had disease progression, with a median time between SOT and IBD progression of 2.2 (interquartile range, 1.3-4.6) years. In the de novo cohort, 55% of patients had disease progression with a median time to flare of 1.9 (interquartile range, 0.8-3.9) years after diagnosis. In the pre-existing IBD cohort, active IBD at the time of SOT (hazard ratio, 1.80; 95% confidence interval, 1.14-2.84; P = .012) and the presence of extraintestinal manifestations (hazard ratio, 3.10; 95% confidence interval, 1.47-6.54; P = .003) were predictive factors for IBD progression. CONCLUSIONS: One-third of patients with pre-existing IBD and about half of patients with de novo IBD have disease progression after SOT. Active IBD at the time of SOT and the presence of extraintestinal manifestations were identified as risk factors for IBD progression.

Real-world long-term effectiveness of ustekinumab in ulcerative colitis: results from a spanish open-label cohort.

OBJECTIVE: Ustekinumab was recently approved for the treatment of moderate-to-severe ulcerative colitis (UC). Although data from the UNIFI clinical trial are encouraging, real-world data assessing effectiveness and safety are scarce. The aim of this study was to assess the effectiveness, safety and pharmacokinetics of ustekinumab in a large cohort of refractory UC patients. METHODS: Multicenter observational study of UC patients who received ustekinumab for active disease. The Partial Mayo Score (PMS), endoscopic activity, C-reactive protein (CRP) and faecal calprotectin (FC) were recorded at baseline and at different time points. Demographic and clinical data, adverse events (AEs) and surgeries were documented. RESULTS: A total of 108 patients were analyzed from 4 referral Spanish hospitals. The clinical remission rates were 59%, 56.5%, 57% and 69% of patients at weeks 8, 16, 24 and 52, respectively. Normalization of FC was achieved in 39.6%, 41% and 51% at weeks 8, 24 and 52, respectively. CRP normalization was observed in 79%, 75% and 76.5% of patients at weeks 8, 24 and 52, respectively. Fewer previous anti-TNF agents and loss of response to anti-TNF were associated with clinical response and normalization of FC, respectively. AEs were observed in 5 patients, and 9 underwent colectomy. Ustekinumab persistence rates were 91%, 83% and 81% at 24, 48 and 96 weeks, respectively. CONCLUSIONS: Ustekinumab demonstrated, in the real-world setting, long-term effectiveness and a favorable safety profile in a cohort of refractory UC patients.

Is Occupation a Risk Factor for Developing Inflammatory Bowel Disease? A Case-Control Study.

Background and aims: The role of occupation is uncertain in the onset of inflammatory bowel diseases. The aim of this study is to identify if there is a role of occupation in these diseases. Materials and methods: A case-control study with incident cases with inflammatory bowel diseases was designed. Cases and controls were recruited simultaneously and controls followed a sex and age frequency matching with cases. A detailed questionnaire was completed by all the participants. To analyze the results, a logistic regression was used. A subgroup analysis was performed for each inflammatory bowel disease. Results: A total of 141 patients with incident inflammatory bowel disease (80 ulcerative colitis, 55 Crohn's disease, and 6 unclassified colitis) and 114 controls were included. There were no statistically significant differences in type of work, working hours, contact with animals, or physical activity at work between inflammatory bowel disease patients and controls. After stratifying results according to type of IBD, there were no statistically significant differences either. Conclusions: There seems to be no risk for inflammatory bowel disease onset regarding the type of work, working hours, contact with animals, or sedentariness.

Real-world outcomes of switching from adalimumab originator to adalimumab biosimilar in patients with inflammatory bowel disease: The ADA-SWITCH study.

BACKGROUND AND AIMS: Data on the outcomes after switching from adalimumab (ADA) originator to ADA biosimilar are limited. The aim was to compare the treatment persistence, clinical efficacy, and safety outcomes in inflammatory bowel disease patients who maintained ADA originator vs. those who switched to ADA biosimilar. METHODS: Patients receiving ADA originator who were in clinical remission at standard dose of ADA originator were included. Patients who maintained ADA originator formed the non-switch cohort (NSC), and those who switched to different ADA biosimilars constituted the switch cohort (SC). Clinical remission was defined as a Harvey-Bradshaw index ≤4 in Crohn's disease and a partial Mayo score ≤2 in ulcerative colitis. To control possible confounding effects on treatment discontinuation, an inverse probability treatment weighted proportional hazard Cox regression was performed. RESULTS: Five hundred and twenty-four patients were included: 211 in the SC and 313 in the NSC. The median follow-up was 13 months in the SC and 24 months in the NSC (p < 0.001). The incidence rate of ADA discontinuation was 8% and 7% per patient-year in the SC and in the NSC, respectively (p > 0.05). In the multivariate analysis, switching from ADA originator to ADA biosimilar was not associated with therapy discontinuation. The incidence rate of relapse was 8% per patient-year in the SC and 6% per patient-year in the NSC (p > 0.05). Six percent of the patients had adverse events in the SC vs. 5% in the NSC (p > 0.05). CONCLUSION: Switching to ADA biosimilar did not impair patients' outcomes in comparison with maintaining on the originator.

Impact of gastrointestinal symptoms and psychological disturbances on patients' quality of life after restrictive or malabsorptive bariatric surgery.

AIM: The aim of this study was to evaluate and compare the presence and impact of Gastrointestinal (GI) symptoms, physical and psychological disturbances on patients' QoL after sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB) and biliopancreatic diversion with duodenal switch (BPD/DS). METHODS: A prospective, observational, cross-sectional, comparative study was carried-out. GI symptoms and patients' QoL were evaluated by the SF-36 questionnaire and the GI quality of life index (GIQLI). Correlation between GI symptoms, psychological disturbances and QoL scores was analysed. RESULTS: 95 patients were included (mean age 50.5 years, range 22-70; 76 females). Presence of GI symptoms was a consistent finding in all patients, and postprandial fullness, abdominal distention and flatulence had a negative impact on patients' QoL. Patients after SG showed a worsening of their initial psychological condition and the lowest QoL scores. Patients after RYGB showed the best GI symptoms-related QoL. CONCLUSIONS: Both restrictive and malabsorptive bariatric surgical procedures are associated with GI symptoms negatively affecting patients' QoL. Compared to SG and BPD/DS, patients after RYGB showed the best GI symptoms-related QoL, which can be used as additional information to help in the clinical decision making of the bariatric procedure to be performed.

Exocrine pancreatic function and dynamic of digestion after restrictive and malabsorptive bariatric surgery: a prospective, cross-sectional, and comparative study.

BACKGROUND: Gastrointestinal anatomical changes after restrictive and malabsorptive bariatric surgery lead to important disturbances in the process of digestion and absorption of nutrients and could lead to exocrine pancreatic insufficiency (EPI). OBJECTIVE: The aim of the present study was to evaluate and to compare pancreatic function and the dynamic of digestion and absorption of nutrients after restrictive and malabsorptive bariatric surgical procedures. SETTING: University Hospital of Santiago de Compostela, Santiago de Compostela, Spain. METHODS: A prospective, observational, cross-sectional, comparative study of patients after sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), and biliopancreatic diversion with duodenal switch (BPD/DS) was carried out. Patients with obesity who did not undergo surgery were included as control group. Pancreatic function and the dynamic of digestion and absorption of nutrients were evaluated by the 13C-mixed triglyceride (13C-MTG) breath test. Six-hour 13C-cumulative recovery rate (13C-CRR), 13C exhalation peak, and 1-hour maximal 13C-CRR were calculated. RESULTS: One-hundred five patients were included (mean age, 49.8 yr; 84 women). Six-hour 13C-CRR was significantly reduced after BPD/DS (P < .001) but not after SG and RYGB. EPI was present in 75% of patients after BPD/DS, 8.3% of patients after RYGB, and 4.3% of patients after SG. Compared with the control group who did not undergo surgery, digestion and absorption of nutrients tended to occur earlier after SG, whereas it was delayed after RYGB and mainly after BPD/DS (P < .001). CONCLUSION: Bariatric surgery significantly alters the dynamic of the digestive process. EPI is very common after BPD/DS, frequent after RYGB, and less frequent after SG. This information is clinically relevant since EPI is a treatable condition associated with symptoms, nutritional deficiencies, and complications.

Endoscopic Pancreatic Drainage Improves Exocrine Pancreatic Function in Patients With Unresectable Pancreatic Cancer: A Double-Blind, Prospective, Randomized, Single-Center, Interventional Study.

OBJECTIVES: Exocrine pancreatic insufficiency is a frequent and clinically relevant complication of pancreatic cancer probably secondary to pancreatic duct obstruction. We aimed at evaluating the impact of endoscopic pancreatic drainage on pancreatic function in patients with unresectable pancreatic cancer. METHODS: A double-blind, prospective, randomized, single-center, interventional study was designed. Patients undergoing endoscopic retrograde cholangiopancreatography for jaundice secondary to unresectable pancreatic cancer were randomized to biliary drainage (group A) or biliopancreatic drainage (group B). Pancreatic function was evaluated by 13C-mixed triglyceride breath test before and 2 weeks after endoscopic retrograde cholangiopancreatography. Breath test result is expressed as 13C-cumulative recovery rate. Abdominal symptoms and nutritional markers were evaluated as secondary outcomes. RESULTS: Twenty patients were included. Sixteen patients had exocrine pancreatic insufficiency, and 13 completed the study (7 in group A and 6 in group B). The median absolute improvement of 13C-cumulative recovery rate was of 23.75% (interquartile range, 9.62-31.74) after biliopancreatic drainage compared with -1.92% (interquartile range, -4.17 to 13.92) after biliary drainage (P = 0.015). Nutritional markers improved after biliopancreatic drainage, but not after biliary drainage. CONCLUSIONS: Biliopancreatic and not biliary endoscopic drainage is associated with a significant improvement of exocrine pancreatic function in patients with unresectable pancreatic cancer.

Bismuth-containing quadruple therapy versus concomitant quadruple therapy as first-line treatment for Helicobacter Pylori infection in an area of high resistance to clarithromycin: A prospective, cross-sectional, comparative, open trial.

BACKGROUND: Concomitant quadruple (CQT) or bismuth-containing quadruple therapy (BQT) is recommended as first-line treatment for Helicobacter pylori infection depending on antibiotic resistance. AIM: To compare the efficacy, safety, and compliance of CQT and BQT as first-line therapy for H. pylori eradication in real clinical practice in an area of high resistance to clarithromycin. METHODS: A prospective, open, comparative cross-sectional study including dyspeptic patients >18 years with H. pylori infection and with no previous eradication treatment was performed. CQT (omeprazole 20 mg + clarithromycin 500 mg + amoxicillin 1 g + metronidazole 500 mg, all given twice daily, for 14 days) or BQT (omeprazole 20 mg twice daily + 3 capsules of Pylera® 4 times a day, for 10 days) was prescribed at the discretion of the prescribing physician. Eradication was tested by 13 C-urea breath test. Efficacy was assessed by intention-to-treat (ITT) and per-protocol (PP) analyses. RESULTS: One hundred and four consecutive patients were included (64.4% female, age 52.9 years). Fifty patients received CQT and 54 BQT. Eradication rate was similar with both therapies at the PP (CQT 97.9%, 95% CI: 93.9-100 vs BQT 96.2%, 95% CI: 90.9-100, P = 0.605) and ITT analyses (CQT 98.0%, 95% CI: 94-100 vs BQT 94.4%, 95% CI: 88.1-100, P = 0.346). The rate of adverse events was also similar with CQT (56%) and BQT (46.3%). One patient in each group discontinued the treatment due to significant adverse events. CONCLUSION: The use of CQT and BQT as first-line treatment against H. pylori is similarly effective and safe strategy in an area of high clarithromycin resistance.

Pancreatic exocrine insufficiency and cardiovascular risk in patients with chronic pancreatitis: A prospective, longitudinal cohort study.

BACKGROUND AND AIM: Previous studies have suggested that chronic pancreatitis (CP) is associated with increased risk of cardiovascular (CV) disease independently of other major risk factors. We evaluated the risk of CV events in a well-phenotyped cohort of patients with CP and its association with pancreatic exocrine insufficiency (PEI) among other CV risk factors. METHODS: This was a prospective, longitudinal cohort study of patients with CP, followed up at the Pancreas Unit of the University Hospital of Santiago de Compostela, Spain. RESULTS: Four hundred thirty patients were included (mean 47.8 ± 14.4 years of age, 79.1% male). Mean follow-up was 8.6 ± 4.6 years. CP etiology was toxic (alcohol and/or smoking) in 290 patients (67.4%). PEI and pancreatogenic diabetes mellitus (DM) were present in 29.3% and 29.5% of the patients, respectively. A total of 45 CV events was recorded (10.5%); 21 patients had a major CV event (stroke or myocardial infarction) and 27 developed clinically relevant peripheral arterial disease. A higher incidence of CV events was recorded in patients with PEI than in those without (incidence rate ratio 3.67, 95% confidence interval [CI] 1.92-7.24; P < 0.001). In the multivariate analysis, PEI without DM (OR 4.96; 95% CI 1.68 to 14.65), coexistence of PEI and DM (OR 6.54; 95% CI 2.71 to 15.77), arterial hypertension (OR 3.40; 95% CI 1.50 to 7.72), and smoking (OR 2.91, 95% CI 1.07 to 7.97) were independently associated with increased CV risk. CONCLUSIONS: Together with known major CV risk factors like smoking and hypertension, PEI is significantly associated with the risk of CV events in patients with CP.

Impact of the treatment of pancreatic exocrine insufficiency on survival of patients with unresectable pancreatic cancer: a retrospective analysis.

BACKGROUND: Malnutrition and weight loss are commonly observed in patients with pancreatic cancer and contribute to poor survival. Pancreatic exocrine insufficiency (PEI), which can be caused by ductal obstruction by a tumor, causes maldigestion and malabsorption of nutrients, thus contributing to malnutrition in these patients. In this study, we evaluated the effects of pancreatic enzyme replacement therapy (PERT) on survival in patients with unresectable pancreatic cancer. METHODS: A retrospective analysis was conducted on a database of patients with unresectable, pathologically confirmed pancreatic cancer. All patients were evaluated for palliative chemotherapy and received the optimal palliative care. Patients were divided into two groups: Group 1 received standard therapy; Group 2 underwent additional evaluation of the pancreatic function and therapy with PERT, if needed. Survival (median and 95% confidence interval [CI]) was analyzed using Kaplan-Meier and Cox regression; groups were compared using the log-rank test. RESULTS: Overall, 160 patients with unresectable pancreatic cancer were included in the analysis (mean age: 70.5 years [range 28-100]; gender: 57.5% male; tumor stage: 78.7% Stage IV). Eighty-six patients (53.75%) were in Group 1 and 74 (46.25%) were in Group 2. Age, gender, tumor size, location and stage, weight loss, and serum CA 19-9 were similar between groups. Ninety-three (58.1%) patients received palliative chemotherapy; 46.5% in Group 1 and 71.6% in Group 2 (P < 0.001). Forty-nine (66.2%) patients in Group 2 and none in Group 1 received PERT. Survival in Group 2 (189 days, 95% CI 167.0-211.0 days) was significantly longer than in Group 1 (95.0 days, 95% CI 75.4-114.6 days) (HR 2.117, 95% CI 1.493-3.002; P < 0.001). Chemotherapy and PERT were significantly and independently associated with longer survival in a model controlled by age and tumor stage. In patients with significant weight loss at diagnosis (> 10% bodyweight within 6 months), PERT was associated with longer survival (HR 2.52, 95% CI 1.55-4.11; P < 0.001). CONCLUSIONS: In patients with unresectable pancreatic cancer, PERT in patients with PEI was associated with longer survival compared with those not receiving PERT, especially in those experiencing significant weight loss. This finding should guide future prospective clinical trials of similar interventions.

Smoking as a risk factor for complications in chronic pancreatitis.

OBJECTIVES: Several recent studies have demonstrated the association between smoking and chronic pancreatitis (CP). However, less is known about the role of smoking in the development of CP-related complications. Our aim was to investigate the impact of smoking and alcohol consumption on age of onset and complications at CP diagnosis. METHODS: A cross-sectional case-case study was performed within a prospectively collected cohort of patients with CP. Alcohol consumption and smoking habits were assessed using a standardized questionnaire. Morphologic severity was defined based on endoscopic ultrasound criteria for CP and classified as mild (3-4 criteria), moderate (5-6 criteria), and severe (≥7 criteria or calcifications). Pancreatic exocrine insufficiency (PEI) was diagnosed using the C-mixed triglyceride breath test. Odds ratios (OR) with 95% confidence intervals (CI) for CP-related complications were calculated using a case-case design. RESULTS: A total of 241 patients were included. Smoking was associated with PEI (OR [95% CI], 2.4 [1.17-5.16]), calcifications (OR [95% CI], 2.33 [1.10-4.95]), and severe morphologic changes (OR [95% CI], 3.41 [1.31-8.85]) but not with pseudocysts or diabetes. Neither smoking nor alcohol consumption was associated with age of onset. CONCLUSIONS: Tobacco, but not alcohol, is associated with PEI, calcifications, and severe morphologic (≥7 criteria or calcifications) CP at diagnosis. Smoking cessation should be encouraged in patients with CP.

Serum nutritional markers for prediction of pancreatic exocrine insufficiency in chronic pancreatitis.

BACKGROUND: Methods for evaluation of pancreatic exocrine insufficiency (PEI) are expensive, labor intensive, and not available at many institutions. The aim of this study was to investigate if PEI in chronic pancreatitis (CP) can by predicted by nutritional markers in blood. METHODS: A retrospective analysis of a prospectively collected database of CP patients was performed. Diagnosis of CP was based on endoscopic ultrasonography or magnetic resonance imaging. PEI was investigated by the (13)C-mixed triglyceride breath test. Hemoglobin, mean corpuscular volume, lymphocytes, prothrombin time, and serum levels of total protein, albumin, prealbumin, retinol binding protein, cholesterol, triglycerides, amylase, folic acid, vitamin B12, HbA1C, transferrin, ferritin, magnesium and zinc were analyzed. RESULTS: 114 patients were included in the study (97 males, mean age 48.1 years, 54 with alcohol etiology), 38 (33%) suffered from PEI. Magnesium below 2.05 mg/dL, hemoglobin, albumin, prealbumin and retinol binding protein below lower limit of normal and HbA1C above upper limit of normal were associated with PEI in univariate analysis. Magnesium below 2.05 mg/dL detected PEI with a sensitivity, specificity and positive and negative predictive values of 0.88 (95% confidence interval, 0.66-0.97), 0.66 (0.48-0.80), 0.58 (0.39-0.75) and 0.91 (0.73-0.98), respectively. The corresponding values were 1.00 (0.80-1.00), 0.55 (0.38-0.71), 0.52 (0.34-0.69) and 1.00 (0.82-1.00)) if one or more pathological tests among parameters significantly associated with PEI in was used as a positive test for PEI. CONCLUSION: Serum nutritional markers can be used to predict the probability of PEI in CP and provide guidance in decisions on enzyme replacement therapy.