Food-Related Quality of Life and Its Predictors in Inflammatory Bowel Disease.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with dietary restrictions and food- and drink-driven daily life limitations. Food-related quality of life (FR-QoL) is still an under-addressed issue in IBD. AIM: We aimed to study determinants of FR-QoL in an IBD cohort, namely objective measures of disease activity. METHODS: A cross-sectional case-control study was conducted in a Tertiary Hospital, including adult patients with IBD (cases) and blood donors or subjects referred for colorectal polypectomies (controls). Participants answered an anonymous multimodal questionnaire including sociodemographic and clinical data, the validated FR-QoL-29, and the SIBDQ tools. Patients' disease activity was previously assessed by a physician using symptom-based scores and biomarkers (Harvey-Bradshaw index, partial Mayo score, fecal calprotectin). RESULTS: A total of 239 patients with IBD and 126 controls were included. Patients with active disease had poorer FR-QoL than patients in remission (80.0 [56.0-99.0] vs. 103.5 [81.0-129.9], p < 0.001). Still, patients with IBD had significantly lower FR-QoL compared with controls (99.0 [76.0-126.0] vs. 126.0 [102.8-143.0], p < 0.001), irrespective of disease activity. FR-QoL correlated with health-related quality of life, measured by SIBDQ (r = 0.490, p < 0.001), and was significantly impaired by patients' depressive humor (84.0 [61.0-112.0] vs. 108.0 [88.0-130.5], p < 0.001). Globally, FR-QoL compromise was mostly related to persistent worries about food, concerns about food-related symptoms, and life disruption due to eating and drinking. CONCLUSIONS: Patients with IBD showed significant FR-QoL impairment, irrespective of disease type and activity. Related psychosocial factors, such as the patient's affective status and fear around eating, warrant a need for a multidisciplinary approach to IBD, including tailored nutritional counseling.

Targeted intervention to achieve waste reduction in gastrointestinal endoscopy.

OBJECTIVE: Endoscopy is healthcare's third largest generator of medical waste in hospitals. This prospective study aimed to measure a single unit's waste carbon footprint and perform a pioneer intervention towards a more sustainable endoscopy practice. The relation of regulated medical waste (RMW; material fully contaminated with blood or body fluids or containing infectious agents) versus landfill waste (non-recyclable material not fully contaminated) may play a critical role. DESIGN: In a four-stage prospective study, following a 4-week observational audit with daily weighing of both waste types (stage 1), stage 2 consisted of a 1-week intervention with team education of waste handling. Recycling bins were placed in endoscopy rooms, landfill and RMW bins were relocated. During stages 3 (1 month after intervention) and 4 (4 months after intervention), daily endoscopic waste was weighed. Equivalence of 1 kg of landfill waste to 1 kg carbon dioxide equivalent (CO2e) and 1 kg of RMW to 3kgCO2e was assumed. Paired samples t-tests for comparisons. RESULTS: From stage 1 to stage 3, mean total waste and RMW were reduced by 12.9% (p=0.155) and 41.4% (p=0.010), respectively, whereas landfill (p=0.059) and recycling waste increased (paper: p=0.001; plastic: p=0.007). While mean endoscopy load was similar (46.2 vs 44.5, p=0.275), a total decrease of CO2e by 31.6% (138.8kgCO2e) was found (mean kgCO2e109.7 vs 74.9, p=0.018). The annual reduction was calculated at 1665.6kgCO2e. All these effects were sustained 4 months after the intervention (stage 4) without objections by responsible endoscopy personnel. CONCLUSION: In this interventional study, applying sustainability measures to a real-world scenario, RMW reduction and daily recycling were achieved and sustained over time, without compromising endoscopy productivity.

Comparison of different histological indexes in the assessment of UC activity and their accuracy regarding endoscopic outcomes and faecal calprotectin levels.

OBJECTIVE: Histological remission is being increasingly acknowledged as a therapeutic endpoint in patients with UC. The work hereafter described aimed to evaluate the concordance between three histological classification systems-Geboes Score (GS), Nancy Index (NI) and RobartsHistopathologyIndex (RHI), as well as to evaluate their association with the endoscopic outcomes and the faecal calprotectin (FC) levels. DESIGN: Biopsy samples from 377 patients with UC were blindly evaluated using GS, NI and RHI. The results were compared with the patients' Mayo Endoscopic Score and FC levels. RESULT: GS, NI and RHI have a good concordance concerning the distinction between patients in histological remission or activity. RHI was particularly close to NI, with 100% of all patients classified as being in remission with NI being identified as such with RHI and 100% of all patients classified as having activity with RHI being identified as such with NI. These scores could also predict the Mayo Endoscopic Score and the FC levels, with their sensitivity and specificity levels depending on the chosen cut-offs. Moreover, higher FC levels were statistically associated with the presence of neutrophils in the epithelium, as well as with ulceration or erosion of the intestinal mucosa. CONCLUSIONS: GS, NI and RHI histopathological scoring systems are comparable in what concerns patients' stratification into histological remission/activity. Additionally, FC levels are increased when neutrophils are present in the epithelium and the intestinal mucosa has erosions or ulcers. The presence of neutrophils in the epithelium is, indeed, the main marker of histological activity.

New cross-sectional imaging in IBD.

PURPOSE OF REVIEW: Cross-sectional imaging, namely ultrasound, CT and MR enterography, complements clinical and endoscopic monitoring of activity and complications in IBD, and emerging new radiological technologies may have clinical applications in the near future. This review offers an update on the potential role of these new imaging methods in the management of IBD. RECENT FINDINGS: Specific MR techniques [diffusion-weighted imaging (DWI), diffusion kurtosis imaging (DKI) and magnetization transfer] allow accurate detection of inflammation (DWI and maybe DKI) and fibrosis (magnetization transfer) in Crohn's disease, without the need of intravenous gadolinium administration. ultrasonography developments (elastography, contrast-enhanced ultrasonography, small intestine contrast ultrasonography and multispectral optoacoustic tomography) are promising techniques for evaluation of fibrosis (elastography) and inflammation (contrast ultrasonography). Dose-reduction techniques in CT allow similar quality imaging and diagnostic accuracy with lower radiation exposure. Hybrid imaging (PET/MR and PET/CT) hold promise for grading inflammation in Crohn's disease. SUMMARY: The potential benefits of new cross-sectional imaging techniques in IBD include better inflammation grading, such as identification of mild degree of activity, which may be relevant whenever assessing response to treatment and, of uttermost importance, accurate preoperative detection and grading of fibrosis in stricturing Crohn's disease, facilitating surgical vs. medical therapeutic decisions.

The influence of subclinical active inflammation on IFX pharmacokinetic modeling and disease progression assessment: findings from a prospective real-world study in inflammatory bowel disease patients.

BACKGROUND AND AIMS: Effective management of inflammatory bowel disease (IBD) relies on a comprehensive understanding of infliximab (IFX) pharmacokinetics (PK). This study's primary goal was to develop a robust PK model, identifying key covariates influencing IFX clearance (CL), while concurrently evaluating the risk of disease progression during the maintenance phase of IBD treatment. METHODS: The multicenter, prospective, real-world DIRECT study was conducted in several care centers, which included 369 IBD patients in the maintenance phase of IFX therapy. A two-compartment population PK model was used to determine IFX CL and covariates. Logistic and Cox regressions were applied to elucidate the associations between disease progression and covariates embedded in the PK model. RESULTS: The PK model included the contributions of weight, albumin, antidrug antibody (ADA), and fecal calprotectin (FC). On average, higher ADA, FC concentration and weight, and lower albumin concentration resulted in higher IFX CL. In the multivariate regression analyses, FC levels influenced the odds of disease progression in all its different definitions, when adjusted for several confounding factors. Additionally, alongside FC, both IFX and CL demonstrated a significant impact on the temporal aspect of disease progression. CONCLUSION: In this 2-year real-world study, readily available clinical covariates, notably FC, significantly impacted IFX availability in IBD patients. We demonstrated that subclinical active inflammation, as mirrored by FC or CRP, substantially influenced IFX clearance. Importantly, FC emerged as a pivotal determinant, not only of IFX pharmacokinetics but also of disease progression. These findings underscore the need to integrate FC into forthcoming IFX pharmacokinetic models, amplifying its clinical significance.

Thiopurines have no impact on outcomes of Crohn's disease patients beyond 12 months of maintenance treatment with infliximab.

BACKGROUND: The emergence of new treatments the inflammatory bowel diseases (IBD) raised questions regarding the role of older agents, namely thiopurines. AIMS: To clarify the benefits of combination treatment with thiopurines on Crohn's disease (CD) patients in the maintenance phase of infliximab. METHODS: In this analysis of the 2-year prospective multicentric DIRECT study, patients were assessed in terms of clinical activity, faecal calprotectin (FC), C-reactive protein (CRP), and infliximab pharmacokinetics. A composite outcome based on clinical- and drug-related items was used to define treatment failure. RESULTS: The study included 172 patients; of these, 35.5 % were treated with combination treatment. Overall, 18 % of patients achieved the composite outcome, without statistically significant differences between patients on monotherapy and on combination treatment (21.6% vs 11.5 %, p = 0.098). Median CRP, FC, and infliximab pharmacokinetic parameters were similar in both groups. However, in the sub-analysis by infliximab treatment duration, in patients treated for less than 12 months, the composite outcome was reached in fewer patients in the combination group than in the monotherapy group (7.1% vs 47.1 %, p = 0.021). CONCLUSION: In CD patients in maintenance treatment with infliximab, combination treatment does not seem to have benefits over infliximab monotherapy beyond 12 months of treatment duration.

The new simplified MARIA score applies beyond clinical trials: A suitable clinical practice tool for Crohn's disease that parallels a simple endoscopic index and fecal calprotectin.

BACKGROUND: A simplified magnetic resonance enterography (MRe) index (sMARIA) for Crohn's disease (CD) was recently developed and validated. OBJECTIVE: Our aims were (a) to assess sMARIA's accuracy in a sample other than the validation cohort; (b) to evaluate its correlation with a simpler endoscopy index (SES-CD) and fecal calprotectin (FC); and (c) to assess the need of an expert radiologist to reliably use sMARIA. METHODS: Patients with CD who underwent MRe, ileocolonoscopy and FC within 2-4 weeks had their MRe retrospectively reviewed by two blinded raters. Disease activity was evaluated through sMARIA, SES-CD and FC. sMARIA's accuracy, indices correlation, and interrater reliability were assessed. RESULTS: In total, 84 patients were included, comprising 420 intestinal segments evaluations. sMARIA ≥1 accurately identified segments with active disease (90% sensitivity, 98% specificity; area under the curve 0.94, 95% confidence interval (CI) 0.91-0.97; p < 0.01). sMARIA correlated with endoscopy, both for ileal and colonic segments (R = 0.94 and R = 0.82; p < 0.01). Per patient, there was a strong correlation between sMARIA, endoscopy (R = 0.95; p < 0.01) and FC (R = 0.91; p < 0.01). Interrater agreement was excellent (intraclass correlation coefficient 0.95; 95% CI 0.94-0.96; p < 0.01). CONCLUSION: sMARIA accurately measured CD activity using SES-CD as standard of reference, and exhibited high correlation with a simple endoscopic index and a biomarker. The interrater reliability between a radiology resident and an expert was excellent.

Therapeutic drug monitoring of CT-P13: a comparison of four different immunoassays.

BACKGROUND: The commercialization of CT-P13, an infliximab (IFX) biosimilar, has the potential to decrease health-related costs and enhance access to biological therapies. This study aimed to address the accuracy and inter-assay agreement of the CT-P13 quantification using four different assays initially developed to assess IFX. METHODS: The four different methods, one in-house method and three commercially available kits, were used to quantify exogenously-spiked samples and the sera from 185 inflammatory bowel disease (IBD) patients on CT-P13 therapy. RESULTS: The quantification of the spiked samples unveiled a consistent and accurate behaviour of three of the tested methods, with average percentage recoveries of 90%, 102% and 109%. Results from the clinical samples demonstrated that these three assays were also highly correlated, both concerning Spearman's rank coefficients (range 0.890-0.947) and intraclass correlation coefficients (range 0.907-0.935). There were a few systematic deviations among them, but their impact in the clinical stratification of the patients using different cut-offs was minimal, particularly when these cut-offs were in the 3-4 µg/ml range, for which the strength of agreement (as assessed by the Kappa statistics that ranged from 0.732 to 0.902) was substantial to almost perfect. CONCLUSIONS: Our results indicate that three of the tested IFX quantification methods can be used to accurately quantify CT-P13 without any adjustments.

Clinical performance of an infliximab rapid quantification assay.

BACKGROUND: Therapeutic drug monitoring (TDM)-based algorithms can be used to guide infliximab (IFX) adjustments in inflammatory bowel disease (IBD) patients. This study aimed to explore a rapid IFX-quantification test from a clinical perspective. METHODS: This manuscript describes a prospective cohort study involving 110 ulcerative colitis (UC) patients on the maintenance phase of IFX. IFX trough levels were quantified using a rapid quantification assay and a commonly-used reference kit. RESULTS: Irrespective of the assay used to measure IFX, its through levels were statistically different between patients with and without endoscopic remission (Mayo endoscopic score = 0), as well as between patients stratified by their faecal calprotectin (FC) levels. Despite the fact that the two methods correlated well with each other [Spearman's rank correlation coefficient = 0.843, p < 0.001; intraclass correlation coefficients = 0.857, 95% confidence interval (CI): 0.791-0.903], there was a discernible systematic variation; values obtained with the reference kit were on average 2.62 units higher than those obtained with the rapid assay. Notwithstanding, 3 µg/ml was shown to be an acceptable cut-off to assess endoscopic status and inflammatory burden levels using both assays. The percentage of patients that had a positive outcome when the IFX concentration measured by the rapid assay ranked above 3 µg/ml was 88% both for a Mayo endoscopic score ⩽ 1 and for an FC concentration <250 µg/g. CONCLUSIONS: Based on this study, we concluded that using the rapid IFX assessment system with a 3 µg/ml threshold is a reliable alternative to the time-consuming enzyme-linked immunosorbent assays in patients on the maintenance phase of IFX.

Development and Validation of Risk Matrices for Crohn's Disease Outcomes in Patients Who Underwent Early Therapeutic Interventions.

INTRODUCTION: The establishment of prognostic models for Crohn's disease [CD] is highly desirable, as they have the potential to guide physicians in the decision-making process concerning therapeutic choices, thus improving patients' health and quality of life. Our aim was to derive models for disabling CD and reoperation based solely on clinical/demographic data. METHODS: A multicentric and retrospectively enrolled cohort of CD patients, subject to early surgery or immunosuppression, was analysed in order to build Bayesian network models and risk matrices. The final results were validated internally and with a multicentric and prospectively enrolled cohort. RESULTS: The derivation cohort included a total of 489 CD patients [64% with disabling disease and 18% who needed reoperation], while the validation cohort included 129 CD patients with similar outcome proportions. The Bayesian models achieved an area under the curve of 78% for disabling disease and 86% for reoperation. Age at diagnosis, perianal disease, disease aggressiveness and early therapeutic decisions were found to be significant factors, and were used to construct user-friendly matrices depicting the probability of each outcome in patients with various combinations of these factors. The matrices exhibit good performance for the most important criteria: disabling disease positive post-test odds = 8.00 [2.72-23.44] and reoperation negative post-test odds = 0.02 [0.00-0.11]. CONCLUSIONS: Clinical and demographical risk factors for disabling CD and reoperation were determined and their impact was quantified by means of risk matrices, which are applicable as bedside clinical tools that can help physicians during therapeutic decisions in early disease management.

Calprotectin and the Magnitude of Antibodies to Infliximab in Clinically-stable Ulcerative Colitis Patients are More Relevant Than Infliximab Trough Levels and Pharmacokinetics for Therapeutic Escalation.

Although infliximab (IFX) is an efficient therapy for ulcerative colitis (UC) patients, a considerably high rate of therapeutic failures still occurs. This study aimed at a better understanding of IFX pharmacokinetics and pharmacodynamics among clinically-asymptomatic UC patients. This was a multicentric and prospective study involving 65 UC patients in the maintenance phase of IFX therapy. There were no significant differences between patients with positive and negative clinical, endoscopic and histological outcomes concerning their IFX trough levels (TLs), area under the IFX concentration vs. time curve (AUC), clearance and antibodies to infliximab (ATI) levels. However, the need to undergo therapeutic escalation later in disease development was significantly associated with higher ATI levels (2.62µg/mL vs. 1.15µg/mL, p=0.028). Moreover, and after adjusting for disease severity, the HR (hazard ratio) for therapeutic escalation was significantly decreased for patients with an ATI concentration below 3µg/mL (HR=0.119, p=0.010), and increased for patients with fecal calprotectin (FC) level above 250µg/g (HR=9.309, p=0.018). In clinically-stable UC patients, IFX pharmacokinetic features cannot predict therapeutic response on a short-term basis. However, high levels of ATIs or FC may be indicative of a future therapeutic escalation.

Primary squamous cell carcinoma of the most distal rectum: a dilemma in origin and management.

Squamous cell carcinoma (SCC) of the rectum is a rare malignant entity that has been classically managed with a surgery-based approach, which included abdominoperineal resection for distal lesions. Recently there have been reports on the favourable outcomes achieved with the non-surgical management of these patients. We report a case of a 52-year-old woman who was diagnosed with a stage IIIa SCC located on the distal rectum. The patient was managed conservatively with a chemoradiation regime with mitomycin and 5-fluorouracil. Complete remission was achieved and she is currently alive, asymptomatic and disease-free after 30 months. This case adds to the existing evidence that supports the role of chemoradiation as a first-line curative treatment for the rare rectal SCC.

Health-related quality of life and utilities in gastric premalignant conditions and malignant lesions: a multicentre study in a high prevalence country.

BACKGROUND AND AIMS: A recent review of economic studies relating to gastric cancer revealed that authors use different tests to estimate utilities in patients with and without gastric cancer. Our aim was to determine the utilities of gastric premalignant conditions and adenocarcinoma with a single standardized health measure instrument. METHODS: Cross-sectional nationwide study of patients undergoing upper endoscopy (n=1,434) using the EQ-5D-5L quality of life (QoL) questionnaire. RESULTS: According to EQ-5D-5L, utilities in individuals without gastric lesions were 0.78 (95% confidence interval: 0.76-0.80), with gastric premalignant conditions 0.79 (0.77-0.81), previously treated for gastric cancer 0.77 (0.73-0.81) and with present cancer 0.68 (0.55-0.81). Self-reported QoL according to the visual analogue scale (VAS) for the same groups were 0.67 (0.66-0.69), 0.67 (0.66-0.69), 0.62 (0.59-0.65) and 0.62 (0.54-0.70) respectively. Utilities were consistently lower in women versus men (no lesions 0.71 vs. 0.78; premalignant conditions 0.70 vs. 0.82; treated for cancer 0.72 vs. 0.78 and present cancer 0.66 vs. 0.70). CONCLUSION: The health-related QoL utilities of patients with premalignant conditions are similar to those without gastric diseases whereas patients with present cancer show decreased utilities. Moreover, women had consistently lower utilities than men. These results confirm that the use of a single standardized instrument such as the EQ-5D-5L for all stages of the gastric carcinogenesis cascade is feasible and that it captures differences between conditions and gender dissimilarities, being relevant information for authors pretending to conduct further cost-utility analysis.

Upper gastrointestinal bleeding in cirrhosis: varix or no varix?

Upper gastrointestinal bleeding from variceal origin is a frequent complication in the cirrhotic population. Duodenal variceal haemorrhage, however, is infrequent and the endoscopic management of such lesions is not straightforward. Non-endoscopic options include vasoactive drugs, transjugular intrahepatic portosystemic shunt (TIPS), transvenous obliteration and surgery as rescue therapy. We present a patient with Child-Pugh A hepatitis C virus-cirrhosis with acute bleeding from a duodenal varix. It was managed with elastic band ligation but late rebleeding occurred after 6 weeks. Gastroduodenoscopy revealed active bleeding from the ligation eschar. Band ligation and sclerosis were attempted but unsuccessful. Terlipressin was started and the patient referred for TIPS. Surprisingly, angiography showed a normal hepatic vein pressure gradient; therefore, TIPS was not performed. Haemorrhage ceased with medical treatment alone. The patient remained stable and was discharged after 10 days, being currently under evaluation for hepatitis C therapy.