Variation in Colonoscopy Performance Measures According to Procedure Indication.

BACKGROUND & AIMS: Most fulfillment and benchmarking information for colonoscopy quality indicators has been obtained from studies of primary screening colonoscopies. We analyzed differences in the fulfillment of colonoscopy quality indicators based on the indication for endoscopy. METHODS: We performed an observational, multicenter, cross-sectional study of 14,867 patients who underwent endoscopy procedures for gastrointestinal symptoms (40.3%), a positive result from a fecal immunochemical test (36.0%), postpolypectomy surveillance (15.3%), or primary screening (8.4%), from February 2016 through December 2017 at 14 centers in Spain. We evaluated rates of adequate colon cleansing, cecal intubation, adenoma detection, and colorectal cancer detection, among others. We used findings from primary screening colonoscopies as the reference standard. RESULTS: Fewer than 90% of patients had adequate bowel preparation; 83.1% of patients with gastrointestinal symptoms had adequate bowel preparation (odds ratio [OR] compared with patients with primary screening colonoscopies, 0.62; 95% CI, 0.49-0.78) and 85.3% of patients receiving postpolypectomy surveillance had adequate bowel preparation (OR, 0.71; 95% CI, 0.55-0.91). The cecal intubation rate was also lower in patients with gastrointestinal symptoms (93.1%) (OR, 0.34; 95% CI, 0.22-0.52). The adenoma detection rate was higher in patients with a positive result from a fecal immunochemical test (46.4%) (OR, 2.01; 95% CI, 1.71-2.35) and in patients undergoing postpolypectomy surveillance (48.2%) (OR, 1.41; 95% CI, 1.20-1.67). The highest proportion of patients with colorectal cancer was in the gastrointestinal symptom group (5.1%) (OR, 5.24; 95% CI, 2.30-11.93) and the lowest was in patients undergoing surveillance (0.8%) (OR, 0.83; 95% CI, 0.32-2.14). CONCLUSIONS: Fulfillment of colonoscopy performance measures varies substantially by indication. Policies addressing performance measures beyond colonoscopy screening procedures should be developed. Benchmarking recommendations could be adjusted according to colonoscopy indication.

International and multicenter real-world study of sorafenib-treated patients with hepatocellular carcinoma under dialysis.

BACKGROUND & AIMS: Information on safety and efficacy of systemic treatment in patients with hepatocellular carcinoma (HCC) under dialysis are limited due to patient exclusion from clinical trials. Thus, we aimed to evaluate the rate, prevalence, tolerability, and outcome of sorafenib in this population. METHODS: We report a multicenter study comprising patients from Latin America and Europe. Patients treated with sorafenib were enrolled; demographics, dose modifications, adverse events (AEs), treatment duration, and outcome of patients undergoing dialysis were recorded. RESULTS: As of March 2018, 6156 HCC patients were treated in 44 centres and 22 patients were concomitantly under dialysis (0.36%). The median age was 65.5 years, 40.9% had hepatitis C, 75% had Child-Pugh A, and 85% were Barcelona Clinic Liver Cancer-C. The median time to first dose modification, treatment duration and overall survival rate were 2.4 months (interquartile ranges [IQR], 0.8-3.8), 10.8 months (IQR, 4.5-16.9), and 17.5 months (95% CI, 7.2-24.5), respectively. Seventeen patients required at least 1 dose modification. The main causes of first dose modification were asthenia/worsening of Eastern Cooperative Oncology Group-Performance Status and diarrhoea. At the time of death or last follow-up, four patients were still on treatment and 18 had discontinued sorafenib: 14 were due to tumour progression, 2 were sorafenib-related, and 2 were non-sorafenib-related AE. CONCLUSIONS: The outcomes observed in this cohort seem comparable to those in the non-dialysis population. Thus, to the best of our knowledge, this is the largest and most informative dataset regarding systemic treatment outcomes in HCC patients undergoing dialysis.

Graft survival after liver transplantation: an approach to a new Spanish risk index.

INTRODUCTION: several indicators are available to assess liver graft survival, including the American DRI and the European ET-DRI. However, there are significant differences between transplant programs of different countries, and the previously mentioned indicators might be not valid in our setting. OBJECTIVES: the aim of the study was to describe a new national liver graft risk indicator based on the results obtained from the Registro Español de Trasplante Hepático (RETH) and to validate the DRI and ET-DRI indicators. METHODS: the RETH includes a Cox analysis of factors associated with graft survival; the graft risk index (GRI) indicator was defined based on these results. The variables considered are dependent upon the donation conditions (age, cause of death, blood compatibility and cold ischemia time) and the transplant recipient (age, underlying disease, hepatitis C virus, transplant number, UNOS status and surgical technique). A logistic regression curve was obtained and graft survival curves were calculated by stratification. Precision was assessed using the ROC analysis. RESULTS: a GRI of 1 represents a probability of graft loss of 23.25%; each point increase in the GRI score multiplies this probability by 1.33. The best discrimination of GRI was obtained by stratification. The DRI ROC area was 0.54 (95% CI, 0.50-0.59) and the ET-DRI ROC area was 0.56 (95% CI, 0.51-0.61), compared to 0.70 (95% CI, 0.65-0.73) (p < 0.0001) for the GRI. CONCLUSIONS: both the DRI and ET-DRI do not seem to be useful in our setting. Hence a national indicator is more desirable. The GRI requires a national study in order to further streamline and assess this indicator.

A comparison of survival in patients with hepatocellular carcinoma and portal vein invasion treated by radioembolization or sorafenib.

BACKGROUND & AIMS: Sorafenib (SOR) is the standard of care for patients with hepatocellular carcinoma (HCC) and portal vein invasion (PVI), based on the results of phase 3 trials. However, radioembolization (RE) using yttrium-90 microspheres has been shown to achieve higher response rates and better survival in large cohorts and phase 2 trials. This study aimed to compare survival of HCC patients with PVI treated by RE or SOR. METHODS: Survival among patients with HCC and PVI treated with RE or SOR in four Spanish hospitals between 2005 and 2013 was analysed retrospectively. Kaplan-Meier survival curves were plotted and baseline variables tested for prognostic value using the log-rank test. A multivariate prognostic model including variables identified in the univariate analysis and adjusted by a propensity score based on factors that may determine the probability of exposure to RE was generated using Cox regression analyses. RESULTS: After a median follow-up of 6 months, 60 deaths had occurred: 38 and 22 in SOR and RE groups respectively. Median survival was 6.7 months (95%CI 5.2-8.1 months) for the entire cohort, and 8.8 months (95%CI 1.8-15.8) in the RE group and 5.4 months (95%CI 2.7-8.1) in the SOR group (P = 0.047). The difference in survival was still statistically significant when 13 patients in the RE group who started SOR after a median time of 8 months were censored from the analysis. CONCLUSIONS: In a cohort of patients with HCC and PVI treatment with RE was associated with a more prolonged survival compared with SOR.

Medical Treatment of Diverticular Disease: Antibiotics.

Diverticular disease (DD) of the colon represents the most common disease affecting the large bowel in western countries. Its prevalence is increasing. Recent studies suggest that changes in gut microbiota could contribute to development of symptoms and complication. For this reason antibiotics play a key role in the management of both uncomplicated and complicated DD. Rifaximin has demonstrated to be effective in obtaining symptoms relief at 1 year in patients with uncomplicated DD and to improve symptoms and maintain periods of remission following acute colonic diverticulitis (AD). Despite absence of data that supports the routine use of antibiotic in uncomplicated AD, they are recommended in selected patients. In patients with AD that develop an abscess, conservative treatment with broad-spectrum antibiotics is successful in up to 70% of cases. In patients on conservative treatment where percutaneous drainage fails or peritonitis develops, surgery is considered the standard therapy. In conclusion antibiotics seem to remain the mainstay of treatment in symptomatic uncomplicated DD and AD. Inpatient management and intravenous antibiotics are necessary in complicated AD, while outpatient management is considered the best strategy in the majority of uncomplicated patients.

A Point-of-Care Faecal Test Combining Four Biomarkers Allows Avoidance of Normal Colonoscopies and Prioritizes Symptomatic Patients with a High Risk of Colorectal Cancer.

Most colonoscopies performed to evaluate gastrointestinal symptoms detect only non-relevant pathologies. We aimed to evaluate the diagnostic accuracy of a qualitative point-of-care (POC) test combining four biomarkers (haemoglobin, transferrin, calprotectin, and lactoferrin), a quantitative faecal immunochemical test (FIT) for haemoglobin, and a quantitative faecal calprotectin (FC) test in symptomatic patients prospectively recruited. Colorectal cancer (CRC), adenoma requiring surveillance, inflammatory bowel disease (IBD), microscopic colitis, and angiodysplasia were considered significant pathologies. A total of 571 patients were included. Significant pathology was diagnosed in 118 (20.7%), including 30 CRC cases (5.3%). The POC test yielded the highest negative predictive values: 94.8% for a significant pathology and 100% for CRC or IBD if the four markers turned negative (36.8% of the patients). Negative predictive values of FIT, FC, and its combination for diagnosis of a significant pathology were 88.4%, 87.6%, and 90.8%, respectively. Moreover, the positive predictive value using the POC test was 82.3% for significant pathology when all biomarkers tested positive (6% of the patients), with 70.6% of these patients diagnosed with CRC or IBD. The AUC of the POC test was 0.801 (95%CI 0.754-0.848) for the diagnosis of a significant pathology. Therefore, this POC faecal test allows the avoidance of unnecessary colonoscopies and prioritizes high risk symptomatic patients.

Evaluation and Management of Nutritional Consequences of Chronic Liver Diseases.

Liver diseases are the major predisposing conditions for the development of malnutrition, sarcopenia, and frailty. Recently, the mechanism of the onset of these complications has been better established. Regardless of the etiology of the underlying liver disease, the clinical manifestations are common. The main consequences are impaired dietary intake, altered macro- and micronutrient metabolism, energy metabolism disturbances, an increase in energy expenditure, nutrient malabsorption, sarcopenia, frailty, and osteopathy. These complications have direct effects on clinical outcomes, survival, and quality of life. The nutritional status should be assessed systematically and periodically during follow-up in these patients. Maintaining and preserving an adequate nutritional status is crucial and should be a mainstay of treatment. Although general nutritional interventions have been established, special considerations are needed in specific settings such as decompensated cirrhosis, alcohol-related liver disease, and metabolic-dysfunction-associated fatty liver disease. In this review, we summarize the physiopathology and factors that impact the nutritional status of liver disease. We review how to assess malnutrition and sarcopenia and how to prevent and manage these complications in this setting.

Long COVID in Children: A Multidisciplinary Review.

Long COVID syndrome has emerged as a long-lasting consequence of acute SARS-CoV-2 infection in adults. In addition, children may be affected by Long COVID, with potential clinical issues in different fields, including problems in school performance and daily activities. Yet, the pathophysiologic bases of Long COVID in children are largely unknown, and it is difficult to predict who will develop the syndrome. In this multidisciplinary clinical review, we summarise the latest scientific data regarding Long COVID and its impact on children. Special attention is given to diagnostic tests, in order to help the physicians to find potential disease markers and quantify impairment. Specifically, we assess the respiratory, upper airways, cardiac, neurologic and motor and psychological aspects. Finally, we also propose a multidisciplinary clinical approach.

How Donor and Surgical Factors Affect the Viability and Functionality of Human Hepatocytes Isolated From Liver Resections.

Liver resections are a significant source of primary human hepatocytes used mainly in artificial liver devices and pharmacological and biomedical studies. However, it is not well known how patient-donor and surgery-dependent factors influence isolated hepatocytes' yield, viability, and function. Hence, we aimed to analyze the impact of all these elements on the outcome of human hepatocyte isolation. Patients and methods: Hepatocytes were isolated from liver tissue from patients undergoing partial hepatectomy using a two-step collagenase method. Hepatocyte viability, cell yield, adhesion, and functionality were measured. In addition, clinical and analytical patient variables were collected and the use or absence of vascular clamping and its type (continuous or intermittent) plus the ischemia times during surgery. Results: Malignant disease, previous chemotherapy, and male gender were associated with lower hepatocyte viability and isolation cell yields. The previous increase in transaminases was also associated with lower yields on isolation and lower albumin production. Furthermore, ischemia secondary to vascular clamping during surgery was inversely correlated with the isolated hepatocyte viability. An ischemia time higher than 15 min was related to adverse effects on viability. Conclusion: Several factors correlated with the patient and the surgery directly influence the success of human hepatocyte isolation from patients undergoing liver resection.

Factors associated with lesion detection in colonoscopy among different indications.

BACKGROUND AND OBJECTIVE: Different factors may influence colonoscopy performance measures. We aimed to analyze procedure- and endoscopist-related factors associated with detection of colorectal lesions and whether these factors have a similar influence in the context of different colonoscopy indications: positive fecal immunochemical test (+FIT) and post-polypectomy surveillance colonoscopies. METHODS: This multicenter cross-sectional study included adults aged 40-80 years. Endoscopists (N = 96) who had performed ≥50 examinations were assessed for physician-related factors. Adenoma detection rate (ADR), adenomas per colonoscopy rate (APCR), advanced ADR, serrated polyp detection (SDR), and serrated polyps per colonoscopy rate (SPPCR) were calculated. RESULTS: We included 12,932 procedures, with 4810 carried out after a positive FIT and 1967 for surveillance. Of the 96 endoscopists evaluated, 43.8% were women, and the mean age was 41.9 years. The ADR, advanced ADR, and SDR were 39.7%, 17.7%, and 12.8%, respectively. Adenoma detection rate was higher in colonoscopies after a +FIT (50.3%) with a more than doubled advanced ADR compared to non-FIT procedures (27.6% vs. 13.0%) and similar results in serrated lesions (14.7% vs. 13.5%). Among all the detection indicators analyzed, withdrawal time was the only factor independently related to improvement (p < 0.001). Regarding FIT-positive and surveillance procedures, for both indications, withdrawal time was also the only factor associated with a higher detection of adenomas and serrated polyps (p < 0.001). Endoscopist-related factors (i.e., weekly hours dedicated to endoscopy, annual colonoscopy volume and lifetime number of colonoscopies performed) had also impact on lesion detection (APCR, advanced ADR and SPPCR). CONCLUSIONS: Withdrawal time was the factor most commonly associated with improved detection of colonic lesions globally and in endoscopies for + FIT and post-polypectomy surveillance. Physician-related factors may help to address strategies to support training and service provision. Our results can be used for establishing future benchmarking and quality improvement in different colonoscopy indications.

Impact of Liver and Pancreas Diseases on Nutritional Status.

Liver and pancreatic diseases have significant consequences on nutritional status, with direct effects on clinical outcomes, survival, and quality of life. Maintaining and preserving an adequate nutritional status is crucial and should be one of the goals of patients with liver or pancreatic disease. Thus, the nutritional status of such patients should be systematically assessed at follow-up. Recently, great progress has been made in this direction, and the relevant pathophysiological mechanisms have been better established. While the spectrum of these diseases is wide, and the mechanisms of the onset of malnutrition are numerous and interrelated, clinical and nutritional manifestations are common. The main consequences include an impaired dietary intake, altered macro and micronutrient metabolism, energy metabolism disturbances, an increase in energy expenditure, nutrient malabsorption, sarcopenia, and osteopathy. In this review, we summarize the factors contributing to malnutrition, and the effects on nutritional status and clinical outcomes of liver and pancreatic diseases. We explain the current knowledge on how to assess malnutrition and the efficacy of nutritional interventions in these settings.

A Patient Self-Made Point-of-Care Fecal Test Improves Diagnostic Accuracy Compared with Fecal Calprotectin Alone in Inflammatory Bowel Disease Patients.

BACKGROUND: Monitoring inflammatory bowel disease patients may be challenging. Fecal calprotectin is one of the most performed tests. Other fecal biomarkers are less used in clinical practice. Rapid fecal tests that could be performed by patients may be a useful strategy to closely monitor disease activity. METHODS: We performed a prospective observational study including consecutive inflammatory bowel disease patients referred for colonoscopy in a single center. Certest FOB + Transferrin + Calprotectin + Lactoferrin® (Certest Biotec S.L, Zaragoza, Spain), a one-step point-of-care test which simultaneously detects these four biomarkers was performed. Endoscopic inflammatory activity was defined using the Mayo score (≥1) in ulcerative colitis, SES-CD (>3) and Rutgeerts scores (≥1) for Crohn's disease. RESULTS: Out of a total of 106 patients (56.5% female, mean age 51 years), 54 (50.9%) were diagnosed with ulcerative colitis and 52 (49.1%) with Crohn's disease. Endoscopic activity was detected in 42 patients (39.0%). Fecal calprotectin provided the best sensitivity (97.6%), with limited specificity (34.4%). Compared to calprotectin, the other 3 fecal biomarkers showed better specificity (87.5-92.1%) and lower sensitivity (45.2-59.5%). Patients with a negative result in all biomarkers (19/106-17.9%) had 100% (CI 95% 97.4-100) negative predictive value, while patients with the 4 biomarkers positive (13/106-12.3%) had 100% (CI 95% 96.1-100) positive predictive value of endoscopic inflammatory activity. AUROC of this 4 biomarker point-of-care test was 0.845 (95% CI 0.771-0.920), significantly higher than the AUROCs of any of the 4 biomarkers. CONCLUSIONS: This test may be a useful strategy to monitor inflammatory activity in clinical practice by excluding or prioritizing patients in need of a colonoscopy.

The Addition of Other Fecal Biomarkers Does Not Improve the Diagnostic Accuracy of Immunochemical Fecal Occult Blood Test Alone in a Colorrectal Cancer Screening Cohort.

Background: Screening with fecal occult blood test reduces colorectal cancer (CRC) incidence and mortality, and is currently implemented in most countries. However, around 40% of screening colonoscopies are normal. Thus, strategies to avoid these colonoscopies are highly necessary. Adding other fecal biomarkers, such as fecal calprotectin (FC), lactoferrin, and transferrin may be useful, but evidence is scarce. Aims: To evaluate the diagnostic accuracy of fecal occult blood immunochemical test (FIT), FC, and a one-step combo card test for the simultaneous semi-qualitative detection of human hemoglobin (hHb), transferrin (hTf), calprotectin (hCp) and lactoferrin (hLf) in a CRC screening program population. Methods: Single-center, prospective observational study, enrolling patients included in a CRC screening program, referred for a colonoscopy due to a positive FIT test. Participants collected a stool sample prior to bowel preparation, and FIT, FC and the combo semi-qualitative tests were performed on the sample. Sensitivity, specificity, positive and negative predictive values and area under receiver operator curve (AUC) for diagnosis of advanced neoplasia, advanced adenoma and CRC were estimated for each biomarker and their combinations. The primary endpoint of the study was to assess whether these biomarkers could improve the diagnostic accuracy of FIT alone. Results: 336 consecutive patients (64% males) were recruited. Advanced neoplasia was found in 129/336 (38.4%) patients, and of these, 22/336 (6.5%) were diagnosed of CRC. 153/336 (45.5%) colonoscopies were completely normal. The AUC for the diagnosis of advanced neoplasia were 0.725 (95%CI 0.665-0.784) for FIT, 0.477 (95%CI 0.413-0.541) for FC and 0.732 (95%CI 0.674-0.791) for the combination of both (FIT + FC) quantitative tests. The AUCs for the combo test were 0.70 (95%CI 0.641-0.760) for hHb, 0.625 (95%CI 0.562-0.698) for hTf, 0.532 (95%CI 0.469-0.595) for hCp, 0.531 (95%CI 0.466-0.595 ) for hLf and 0.681 (95%CI 0.620-0.741) for the combination of the four biomarkers. Conclusion: In average-risk population, FIT appears to be the best fecal marker for the diagnosis of CRC and advanced adenoma. None of the other biomarkers explored or their combinations provided a better diagnostic accuracy. Only hTF showed an acceptable diagnostic accuracy. FC and hLF were not useful in this setting.

Reducing the Cut-Off Value of the Fecal Immunochemical Test for Symptomatic Patients Does Not Improve Diagnostic Performance.

Introduction: The fecal immunochemical test (FIT) has been established as a cost-effective test in colon cancer screening programmes. This test could also be helpful in symptomatic patients prior to colonoscopy, but data about diagnostic performance, and accurate cut-off values for these patients are still scarce. Materials and Methods: Prospective study that included consecutive unselected patients with gastrointestinal symptoms referred for colonoscopy between November 2016 and June 2018. We performed a FIT (FOB Gold® test, cut-off 20 micrograms of Hb/gram of feces) prior to colonoscopy and determined the accuracy of FIT in terms of sensitivity, specificity, positive and negative predictive value for clinically significant pathology, advanced neoplasia, and colorectal cancer in symptomatic patients, using two different cut-off values. Results: A total of 727 patients (44.3% men, aged 58.5 ± 14.9 years) was included in the study. The main symptom was history of previous (non-active) rectal bleeding (34.7%), followed by diarrhea (15.0%). Over one quarter of the patients (25.9%) had a positive FIT result. The caecal intubation rate was 95.5%. Clinically significant pathology was identified in 142 colonoscopies (19.5%), advanced neoplasia in 115 (15.8%) and colorectal cancer in 36 colonoscopies (5.0%). FIT performed very well for clinically significant pathology, advanced neoplasia and cancer, with a high negative predictive value (NPV). Reducing the cut-off value to 10 µg/g yielded similar NPV results, with a decrease in specificity. Using a combination of symptoms with a positive FIT result did not improve FIT performance. Only specificity was slightly higher compared to FIT alone, but this was paralleled by a decrease in sensitivity and NPV for cancer and clinically significant pathology. The odds of presenting clinically significant pathology, advanced neoplasia, or cancer increased with FIT concentration. Conclusions: The specificity and NPV of FIT for clinically significant pathology, advanced neoplasia, and cancer are high in symptomatic patients. FIT is a helpful test for determining the need to perform further studies. It may not be necessary to reduce the cut-off value for symptomatic patients, since FIT performance with the current standard cut-off value used in colorectal cancer screening was accurate. FIT can be used to avoid or prioritize colonoscopy procedures.

The combination of quantitative faecal occult blood test and faecal calprotectin is a cost-effective strategy to avoid colonoscopies in symptomatic patients without relevant pathology.

BACKGROUND: Faecal occult blood test (FOBT) has demonstrated effectiveness in colorectal cancer (CRC) screening. Faecal calprotectin (FC) has proven efficient for evaluating activity in inflammatory bowel disease (IBD), but its value in CRC detection is less established. Most symptomatic patients have benign pathologies, but still undergo colonoscopy in many settings. AIMS: To evaluate the diagnostic accuracy and cost-effectiveness of the combination of FOBT plus FC in symptomatic patients. METHODS: Patients who completed colonic investigations and returned stool samples, on which FOBT and FC were performed, were recruited prospectively. CRC, advanced adenoma, IBD and angiodysplasia were considered as relevant pathologies. RESULTS: A total of 404 patients were included, of whom 87 (21.5%) had relevant pathologies. Sensitivity and specificity were 50.6% and 69.6% for FOBT, 78.2% and 54.4% for FC. Negative predictive value (NPV) was 90.1% for FC and 86.9% for FOBT. NPV for the combination of FOBT and FC was 94.1%, with a sensitivity and specificity of 88.5% and 50.3%. The area under ROC (receiver operator curve) (AUC) was 0.741 for FOBT, 0.736 for FC and 0.816 for the combination. The total cost for visits and procedures was €233,016 (€577/patient). Using a combination of FOBT and FC as pre-endoscopic tool allows colonoscopies to be reduced by 39.4%, reducing total costs by 20.5%. CONCLUSION: The combination of FOBT and FC has a better diagnostic accuracy compared with each test alone. Performing both tests before colonoscopy is a less costly and more effective strategy, reducing unnecessary procedures and complications.

Donor Age Predicts Calcineurin Inhibitor Induced Neurotoxicity After Liver Transplantation.

BACKGROUND: Calcineurin inhibitor-induced neurotoxicity (CIIN) is a common and debilitating side effect after liver transplantation (LT). Risk factors and impact on patient outcomes are not well defined. Our aim was to assess the incidence, risk factors, and clinical outcomes of CIIN. METHODS: We retrospectively analyzed 175 LTs performed at our center between January 2010 and September 2016. Donor and recipient demographics as well as clinical variables pre-LT, intra-LT, and post-LT were assessed. All patients were on once-daily prolonged-release tacrolimus. RESULTS: CIIN was described in 37 (21.4%) recipients. In univariate analysis, history of hepatic encephalopathy (P = 0.033), immunosuppressant treatment protocol (P = 0.041), donor age (P = 0.002), and pre-LT sodium serum levels (P = 0.004) were associated with CIIN. Patients undergoing LT for hepatocellular carcinoma had lower rates of CIIN (P = 0.040). In multivariate analysis, hepatic encephalopathy (odds ratio [OR], 2.728; 95% confidence interval [CI], 1.098-6.779; P = 0.031), pre-LT serum sodium levels (OR, 1.118 per mEq/L increase, 95% CI, 1.021-1.224; P = 0.016), and donor age (OR, 1.032 per y increase; 95% CI, 1.004-1.062; P = 0.027) were independent risk factors for developing CIIN. In the CIIN group, patients had longer intensive care unit (P = 0.024) and hospital (P = 0.008) stays and more changes in immunosuppressive treatment (54.1% vs 20.4%; P < 0.001). CONCLUSIONS: Neurotoxicity remains frequent in patients on once-daily prolonged-release tacrolimus. Antecedents of hepatic encephalopathy, pre-LT sodium serum levels, and donor age are independent risk factors for developing CIIN after LT. CIIN is associated with longer hospital stays and changes in immunosuppressive treatment.

Young age and tobacco use are predictors of lower medication adherence in inflammatory bowel disease.

BACKGROUND: Medication adherence is crucial in the management of patients with inflammatory bowel disease (IBD) because medication nonadherence in these patients is associated with an increased risk of flare-up, relapse, recurrence, loss of response to anti-tumour necrosis factor agents, morbidity and mortality, and poor quality of life. Data on risk factors are very controversial in the literature. AIM: To assess the prevalence of medication nonadherence and to identify predictors of low medication adherence in Spanish patients with IBD. PATIENTS AND METHODS: We carried out a cross-sectional study that included consecutive outpatients with IBD attending in our adult tertiary clinic in a 3-month period. Morisky 8-Item Medication Adherence Scale questionnaire as well as a survey of sociodemographic data were used. RESULTS: A total of 181 patients were evaluated. Almost half of the patients (46.4%) had high medication adherence, 30.9% had medium adherence, and 22.7% had low adherence. In relation to predictive factors of medication adherence, multivariate analysis showed that age was associated with high adherence [odds ratio (OR): 1.04; 95% confidence interval (CI): 1.01-1.06; P=0.002]. However, being a smoker and presence of Crohn's disease were associated with low adherence (OR: 3.47; 95% CI: 1.36-8.90; P<0.01 and OR: 2.54; 95% CI: 1.12-5.79; P<0.05, respectively). CONCLUSION: Only half of patients were high medication adherers. Young age, active smoking, and Crohn's disease seems to be predictors of low medication adherence. On the basis of these data, efforts for reinforce medication adherence should be especially directed to young patients and smokers.

Biosimilars in inflammatory bowel disease.

The introduction of biologic therapies has revolutionized the treatment of inflammatory bowel disease (IBD) and has significantly improved the disease course and outcomes for many patients. Biologics are the main drivers of cost in many IBD units and biosimilars, although are not better than originators, are usually cheaper and thus can increase the availability of this type of therapy. Biosimilar are highly similar to innovator but, due to the complex structures of innovators and the variability inherent in the manufacturing process, they are no identical. This fact cause concerns with respect to the efficacy and safety in medical community, especially in the medical indications in which no specific clinical trials with biosimilars have been performed as IBD. Nowadays, two biosimilars to infliximab, CT-P13 and SB2, has been approved by European Medicines Agency in all the indications of the reference product. To date, the available evidence suggests that switch from reference medicinal product (infliximab) to the biosimilar (CT-P13 or SB2) is feasible since published studies have not observed significantly difference in terms of efficacy, immunogenicity and safety. However, the experts agreed that by now there is not sufficient evidence to consider infliximab biosimilars interchangeable with the originator compound. In this manuscript, we will review the processes involved in the manufacturing and regulatory approval of biosimilars and examine the evidence presently available on approved biosimilars in Europe for IBD.

Oral Cyanocobalamin is Effective in the Treatment of Vitamin B12 Deficiency in Crohn's Disease.

Cobalamin deficiency is common in patients with Crohn's disease (CD). Intramuscular cobalamin continues to be the standard therapy for the deficiency and maintenance treatment in these patients, although oral route has been demonstrated to be effective in other pathologies with impaired absorption. Our aims were to evaluate the efficacy of oral therapy in the treatment of cobalamin deficiency and in long-term maintenance in patients with Crohn's disease. We performed a multicenter retrospective cohort study that included 94 patients with Crohn's disease and cobalamin deficiency. Seventy-six patients had B12 deficiency and 94.7% of them normalized their cobalamin levels with oral treatment. The most used dose was 1 mg/day, but there were no significant differences in treatment effectiveness depending on the dose used (≥1 mg/24 h vs. <1 mg/24 h). Eighty-two patients had previous documented B12 deficiency and were treated with oral B12 to maintain their correct cobalamin levels. After a mean follow-up of 3 years, the oral route was effective as maintenance treatment in 81.7% of patients. A lack of treatment adherence was admitted by 46.6% of patients in who the oral route failed. In conclusion, our study shows that oral cyanocobalamin provides effective acute and maintenance treatment for vitamin B12 deficiency caused by CD with or without ileum resection.