Association between Ustekinumab Trough Levels, Serum IL-22, and Oncostatin M Levels and Clinical and Biochemical Outcomes in Patients with Crohn's Disease.

Background: Ustekinumab (UST) has demonstrated effectiveness in treating patients with Crohn's disease. Monitoring treatment response can improve disease management and reduce healthcare costs. We investigated whether UST trough levels (TLs), serum IL22, and Oncostatin M (OSM) levels could be early indicators of non-response by analysing their correlation with clinical and biochemical outcomes in CD. Methods: Patients with CD initiating UST treatment from October 2018 to September 2020 were enrolled at six Italian centres for inflammatory bowel disease (IBD). Clinical and biochemical data were collected at four time points: baseline, second subcutaneous (SC) dose, fourth SC dose, and 52 weeks. TLs were measured during maintenance, at the second SC dose, and at the fourth SC dose. IL-22 and OSM serum levels were assessed at baseline and the second SC dose. We analysed whether TLs, IL22 levels, and OSM serum levels were associated with clinical response, clinical remission, biochemical remission, and endoscopic remission using the appropriate statistical tests. Results: Out of eighty-four initially enrolled patients, five were lost to follow-up, and eleven discontinued the drug before 52 weeks. At the 52-week time point, 47% achieved biochemical remission based on faecal calprotectin levels, and 61.8% achieved clinical remission. TLs at the second SC dose significantly correlated with biochemical remission at the same time point (p = 0.011). However, TLs did not correlate with clinical remission. Baseline OSM levels did not correlate with biochemical or clinical remission or response. IL22 levels notably decreased during UST therapy (p = 0.000), but its values did not correlate with biochemical or clinical remission. Conclusions: UST is an effective therapy for patients with CD. TLs measured at the second SC dose significantly correlated with biochemical remission, emphasising their potential role in treatment monitoring. Levels of OSM and IL-22, despite a significant decrease in the latter during therapy, did not exhibit correlations with clinical or biochemical outcomes in our study. Further studies are needed to confirm these findings.

Biliary Tree Diagnostics: Advances in Endoscopic Imaging and Tissue Sampling.

The diagnostic approach to the biliary tree disorders can be challenging, especially for biliary strictures. Albeit the great diagnostic impact of endoscopic retrograde cholangiopancreatography (ERCP) which allows one to obtain fluoroscopic imaging and tissue sampling through brush cytology and/or forceps biopsy, a considerable proportion of cases remain indeterminate, leading to the risk of under/over treated patients. In the last two decades, several endoscopic techniques have been introduced in clinical practice, shrinking cases of uncertainties and improving diagnostic accuracy. The aim of this review is to discuss recent advances and emerging technologies applied to the management of biliary tree disorders through peroral endoscopy procedures.

Rapid point-of-care anti-infliximab antibodies detection in clinical practice: comparison with ELISA and potential for improving therapeutic drug monitoring in IBD patients.

Anti-drug antibodies can interfere with the activity of anti-tumor necrosis factor (TNF) agents by increasing drug clearance via direct neutralization. The presence of anti-drug antibodies is clinically relevant when trough drug concentrations are undetectable or sub-therapeutic. However, traditional immunoassay is not easily and rapidly accessible, making the translation of the results into treatment adjustment difficult. The availability of a point-of-care (POC) test for therapeutic drug monitoring (TDM) might represent an important step forward for improving the management of inflammatory bowel disease (IBD) patients in clinical practice. In this pilot study, we compared the results obtained with POC tests with those obtained by enzyme-linked immunosorbent assay (ELISA) in a group of IBD patients treated with Infliximab (IFX). We showed that POC test can reliably detect presence of antibody-to-IFX with 100% of specificity and 76% sensitivity, in strong agreement with the ELISA test (k-coefficient = 0.84).

Bisacodyl plus split 2-L polyethylene glycol-citrate-simethicone improves quality of bowel preparation before screening colonoscopy.

AIM: To compare the bowel cleansing efficacy, tolerability and acceptability of split 2-L polyethylene glycol (PEG)-citrate-simethicone (PEG-CS) plus bisacodyl (BIS) vs 4-L PEG for fecal occult blood test-positive screening colonoscopy. METHODS: This was a randomised, observer-blind comparative study. Two hundred and sixty-four subjects underwent screening colonoscopy (mean age 62.5 ± 7.4 years, male 61.7%). The primary objective of the study was to compare the bowel cleansing efficacy of the two preparations. INTERVENTIONS: BIS plus PEG-CS: 3 tablets of 5-mg BIS at 16:00, PEG-CS 1-L at 19:00 and 1-L at 7:00, 4-L PEG: 3-L at 17:00, and 1-L at 7:00. Colonoscopy was carried out after 11:00, at least 3 h after the completion of bowel preparation. Bowel cleansing was evaluated using the Harefield Cleansing Scale. RESULTS: Bowel preparation was successful for 92.8% of subjects in the PEG-CS group and for 92.1% of subjects in the 4-L PEG (RR = 1.01; 95%CI: 0.94-1.08). BIS + PEG-CS was better tolerated than 4-L PEG. A greater rate of patients in the BIS + PEG-CS group had no difficulty and/or were willing to repeat the same preparation compared to split-dose 4-L PEG group. Subjects in the BIS + PEG-CS group rated the prep as good or satisfactory in 90.6% as compared to 77% in the 4-L PEG (P = 0.003). Subjects receiving BIS + PEG-CS stated they fully adhered to instructions drinking all the 2-L solution in 97.1% compared with 87.3% in the 4-L PEG (P = 0.003). CONCLUSION: BIS plus split 2-L PEG-CS was as effective as but better tolerated and accepted than split 4-L PEG for screening colonoscopy. This new procedure may increase the positive attitude and participation to colorectal cancer screening colonoscopy.

Prevalence of different subtypes of serrated polyps and risk of synchronous advanced colorectal neoplasia in average-risk population undergoing first-time colonoscopy.

OBJECTIVES: A growing body of evidence indicates that patients with sessile serrated adenoma/polyp (SSA/P) and traditional serrated adenoma (TSA) are at risk for subsequent malignancy. Despite increasing knowledge on histological categorization of serrated polyps (SPs) data are lacking on the actual prevalence and the association of each SP subtype with advanced colorectal neoplasia. METHODS: We prospectively determined the prevalence of different SP subtypes and evaluate the association with synchronous advanced neoplasia in asymptomatic average-risk subjects undergoing first-time colonoscopy. All retrieved polyps were examined by two independent pathologists. Serrated lesions were classified into hyperplastic polyps (HP), SSA/P (without and with cytological dysplasia, SSA/P/DIS), and TSA, and were screened for BRAF and K-ras mutations. RESULTS: Among 258 polyps detected in 985 subjects, the proportion of SSA/P and TSA was 8.9% and 1.9% with an overall prevalence of 2.3% and 0.6%, respectively. SSA/Ps were small without significant difference in their location between proximal and distal colon; TSA were predominantly left-sided. BRAF mutation was common in SSA/Ps and K-ras mutation was present in all TSA. Independent predictors of advanced neoplasia were male sex (odds ratio (OR)=2.0, 95% confidence interval (CI) 1.0-4.0), increasing age (OR=4.5, 95% CI 1.5-13.4 for 50-69 years and OR=9.9, 95% CI 3.1-31.5 for >70 years), current smoking (OR=2.0, 95% CI 1.3-6.8), >3 tubular adenoma (OR=3.6, 95% CI 1.9-6.4), and SSA/P (OR=6.0, 95% CI 1.9-19.5). CONCLUSIONS: The substantial prevalence of BRAF-mutated SSA/P and the independent association with synchronous advanced colorectal neoplasia in asymptomatic average-risk subjects support the overall impact of the serrated pathway on colorectal cancer (CRC) risk in general population. The endoscopic characteristics of SSA/P emphasize the need of high-quality colonoscopy as a key factor for an effective CRC screening program.

A randomized controlled trial evaluating a new 2-L PEG solution plus ascorbic acid vs 4-L PEG for bowel cleansing prior to colonoscopy.

BACKGROUND: Bowel preparation is critical for the efficacy and safety of colonoscopy. Poor patient tolerance to bowel preparation has been associated with the high amount of fluid administered. A 2-L polyethylene glycol (PEG) solution containing ascorbic acid has been recently developed. AIMS: To compare the efficacy, safety and acceptability of 2-L PEG+ascorbic acid vs 4-L PEG for colonoscopy. METHODS: We designed a single blind randomized non-inferiority study in order to compare the two bowel preparations. A blinded assessment of cleansing was made by the endoscopist according to the Aronchick scale. Acceptability was assessed by questionnaire. Intention-to-treat (ITT) and per-protocol (PP) analysis were reported. RESULTS: Overall, 169 patients (PP: 166) were selected for the 2-L PEG+ascorbic acid and 170 (PP: 166) for the 4-L PEG. When rating global bowel cleansing at ITT, an excellent-good level was reported in 84.6% (PP: 86.2%) of patients who received 2-L PEG+ascorbic acid and 75.3% (PP: 77%) of patients who received 4-L PEG (p=0.04). Acceptability rate favoured 2-L PEG+ascorbic acid vs 4-L PEG (83% vs 76%; p=0.02). CONCLUSIONS: 2-L PEG+ascorbic acid, completed with an additional L of clear fluids, provided bowel cleansing which appeared to be more effective and acceptable than 4-L PEG.

Quality of life following organ transplantation.

Organ transplantation is a procedure that can save and prolong the life of individuals with end-stage heart, lung, liver, kidney, pancreas and small bowel diseases. The goal of transplantation is not only to ensure their survival, but also to offer patients the sort of health they enjoyed before the disease, achieving a good balance between the functional efficacy of the graft and the patient's psychological and physical integrity. Quality of life (QoL) assessments are used to evaluate the physical, psychological and social domains of health, seen as distinct areas that are influenced by a person's experiences, beliefs, expectations and perceptions, and QoL is emerging as a new medical indicator in transplantation medicine too. This review considers changes in overall QoL after organ transplantation, paying special attention to living donor transplantation, pediatric transplantation and particular aspects of QoL after surgery, e.g. sexual function, pregnancy, schooling, sport and work.

Understanding of and attitudes to organ donation and transplantation: a survey among Italian university students.

BACKGROUND: Students have a positive attitude to organ donation and transplantation, usually associated with their personal willingness to donate their organs after death. The aim of this study was to evaluate the opinions of university students on transplantation and organ donation, at a single Italian university. METHODS: University undergraduates attending the first year on five different courses in 2001 were surveyed at Padua University by using an anonymous 13-item questionnaire. RESULTS: 97.2% of the students completed the questionnaire (77.4% females, mean age 20.4 yr); they were attending Medicine (33.8%), Agriculture (5.9%), Veterinary Medicine (11.4%), Psychology (18.5%) and Educational Sciences (30.4%). The majority was aware of the problem of the paucity of organ donations and deaths on the waiting list in Italy. Most students would accept transplantation in the case of a human donor (97%), an artificial organ (95%) or an animal donor (76%); and 87% of them were prepared to donate their own organs after death. No differences were seen when students attending science courses were compared with those attending art courses. Italian university students have a very positive attitude and willingness to donate their own organs after death, with no differences emerging as regards type of university education.

Understanding of and attitude to xenotransplantation among Italian university students: impact of a 3-yr university course.

BACKGROUND: Young people, and students in particular, generally have a positive attitude to xenotransplantation. We reported previously that university students attending their first year approved of the idea of transplanting animal organs into humans. The aim of this study was to evaluate the impact of a 3-yr course at various faculties on the university students' understanding of and attitude to xenotransplantation. METHODS: University students in their fourth year at five different faculties of Padua University (Italy), who had previously been surveyed in exactly the same way 3 yr earlier, were re-administered an anonymous 19-item questionnaire on their attitude to xenotransplantation. RESULTS: A total of 453 students completed the fourth year questionnaire (84 males, 369 females; mean age 24.6 yr, range 21-36 yr). Students were attending courses in Medicine (22.1%), Veterinary Science (16.5%), Agriculture (10.4%), Educational Sciences (22.1%) and Psychology (28.9%). In their fourth year, 85% of the students knew that animal organs could, at some stage, be transplanted into humans, 81.5% approved of this idea and 84% would accept an animal organ to save their life if necessary (these percentages were 88%, 78% and 76%, respectively 3 yr earlier). A significantly larger proportion of the students who approved of xenotransplantation were attending science courses rather than art courses, while no differences emerged as regards gender. Those who refused xenotransplantation justified their position mainly on ethical-moral (41.7%) and immunological (35.7%) grounds. CONCLUSION: As in their first year, so too in their fourth, University students were well informed about the feasibility of transplanting animal organs into human beings and those attending science courses were more likely to accept this idea than art students. Approval of xenotransplantation was much the same among fourth year males and females, whereas in the first year, male students had approved more than female students.

Small bowel exploration by wireless capsule endoscopy: results from 314 procedures.

OBJECTIVES: To assess the diagnostic efficiency of capsule endoscopy in a large group of patients with different indications, to weigh the reliability of the procedure for excluding small bowel lesions, and to identify factors associated with the likelihood of obtaining a definitive diagnosis. METHODS: Three hundred four consecutive patients (141 female, mean age 55 years, range 12-91 years) underwent capsule endoscopy in two different Gastroenterology Units, for a total of 314 procedures, and were followed-up for a median period of 15 months. Referrals were obscure occult/overt gastrointestinal bleeding (203 patients), suspected small bowel disease (74), gastrointestinal polyposis (18), suspected/previous intestinal or endocrine malignancies (13), previously diagnosed intestinal lymphangectasia (3), and vascular abnormalities (3). RESULTS: Adequate visualization of the small bowel was obtained in 96% of patients, although the capsule did not visualize cecum in 20% of cases. Non-natural excretion of the capsule was observed in 4 patients, all of whom underwent laparotomy for intestinal stenosis. Diagnostic yields were 58% for obscure gastrointestinal bleeding and 31% for patients with suspected small bowel disease. Capsule endoscopy was able to rule out small bowel disease in 14% of patients, and a definitive diagnosis was achieved in 65% of patients. The only parameter associated with the likelihood of reaching a conclusive diagnosis was the indication to the procedure (overall chi-square 13.5, P = .004). CONCLUSIONS: Capsule endoscopy represents a reliable tool for verifying the state of the small bowel. Accurate selection of indications and critical evaluation of the results are essential to fully exploit this procedure.