Complete Endoscopic Healing Is Associated With Lower Relapse Risk After Anti-TNF Withdrawal in Inflammatory Bowel Disease.

BACKGROUND & AIMS: Discontinuation of anti-tumor necrosis factor-α treatment (anti-TNF) (infliximab and adalimumab) in patients with inflammatory bowel disease (IBD) is associated with a high relapse risk that may be influenced by endoscopic activity at the time of stopping. We assessed the relapse rate after anti-TNF withdrawal in patients with endoscopic healing and studied predictors of relapse including the depth of endoscopic healing. METHODS: This was a multicenter, prospective study in adult patients with Crohn's disease (CD), ulcerative colitis (UC), or IBD-unclassified (IBDU), with ≥6 months of corticosteroid-free clinical remission (confirmed at baseline) and endoscopic healing (Mayo <2/SES-CD <5 without large ulcers), who discontinued anti-TNF between 2018 and 2020 in the Netherlands. We performed Kaplan-Meier and Cox regression analyses to assess the relapse rate and evaluate potential predictors: partial (Mayo 1/SES-CD 3-4) versus complete (Mayo 0/SES-CD 0-2) endoscopic healing, anti-TNF trough levels, and immunomodulator and/or mesalamine use. RESULTS: Among 81 patients (CD: n = 41, 51%) with a median follow-up of 2.0 years (interquartile range, 1.6-2.1), 40 patients (49%) relapsed. Relapse rates in CD and UC/IBDU patients were comparable. At 12 months, 70% versus 35% of patients with partial versus complete endoscopic healing relapsed, respectively (adjusted hazard rate [aHR], 3.28; 95% confidence interval [CI], 1.43-7.50). Mesalamine use was associated with fewer relapses in UC/IBDU patients (aHR, 0.08; 95% CI, 0.01-0.67). Thirty patients restarted anti-TNF, and clinical remission was regained in 73% at 3 months. CONCLUSIONS: The relapse risk was high after anti-TNF withdrawal in IBD patients with endoscopic healing, but remission was regained in most cases after anti-TNF reintroduction. Complete endoscopic healing and mesalamine treatment in UC/IBDU patients decreased the risk of relapse.

A meta-analysis of methotrexate polyglutamates in relation to efficacy and toxicity of methotrexate in inflammatory arthritis, colitis and dermatitis.

AIMS: In immune-mediated inflammatory diseases (IMIDs), early symptom control is a key therapeutic goal. Methotrexate (MTX) is the first-line treatment across IMIDs. However, MTX is underutilized and suboptimally dosed, partly due to the inability of making individualized treatment decisions through therapeutic drug monitoring (TDM). To implement TDM in clinical practice, establishing a relationship between drug concentration and disease activity is paramount. In this meta-analysis, we investigated the relationship between concentrations of MTX polyglutamates (MTX-PG) in erythrocytes and efficacy as well as toxicity across IMIDs. METHODS: Studies analysing MTX-PG in relation to disease activity and/or toxicity were included for inflammatory arthritis (rheumatoid [RA] and juvenile idiopathic arthritis [JIA]), inflammatory bowel disease (Crohn's and ulcerative colitis) and dermatitis (psoriasis and atopic dermatitis). Meta-analyses were performed resulting in several summary effect measures: regression coefficient (ß), correlation coefficient and mean difference (of MTX-PG in responders vs. nonresponders) for IMIDs separately and collectively. RESULTS: Twenty-five studies were included. In RA and JIA, higher MTX-PG was significantly associated with lower disease activity at 3 months (ß: -0.002; 95% confidence interval [CI]: -0.004 to -0.001) and after 4 months of MTX use (ß: -0.003; 95% CI: -0.005 to -0.002). Similarly, higher MTX-PG correlated with lower disease activity in psoriasis (R: -0.82; 95% CI: -0.976 to -0.102). Higher MTX-PG was observed in RA, JIA and psoriasis responders (mean difference: 5.2 nmol/L MTX-PGtotal ; P < .01). CONCLUSION: We showed that higher concentrations of erythrocyte MTX-PG were associated with lower disease activity in RA, JIA and psoriasis. These findings are an important step towards implementation of TDM for MTX treatment across IMIDs.

Potential of Mesalazine Therapeutic Drug Monitoring by Measuring Fecal Excretion in Patients With Ulcerative Colitis.

BACKGROUND: Therapeutic drug monitoring of mesalazine (5-ASA) in patients with ulcerative colitis is unavailable. Mucosal 5-ASA concentrations are assumed to be higher during remission, but biopsy is not practical. Therefore, we investigated the feasibility of measuring mesalazine levels in feces. To explore the potential role of fecal mesalazine measurements in therapeutic drug monitoring, we compared the dry fecal concentration and daily fecal excretion of 5-ASA and its metabolite N-acetyl-5-ASA in patients with ulcerative colitis with active and quiescent disease. METHODS: Adults with ulcerative colitis on oral mesalazine and scheduled for colonoscopy were eligible for inclusion in this cross-sectional study. Stool and urine samples were collected for 48 and 24 hours, respectively, and rectal biopsies were performed. (N-acetyl-)5-ASA was measured using mass spectrometry. Biochemically active disease was defined as a fecal calprotectin level above 100 mcg/g and endoscopically active disease as any activity following the endoscopic Mayo score (≥1). RESULTS: Approximately 28 patients were included in the study. Daily fecal excretion of (N-acetyl-)5-ASA did not differ between patients with (n = 13) and without (n = 15) endoscopically active disease [median 572 mg/d versus 597 mg/d ( P = 0.86) for 5-ASA and 572 mg/d versus 554 mg/d ( P = 0.86) for N-acetyl-5-ASA]. The same applied to the fecal concentration [median 9.7 mcg/mg dry weight versus 10.3 ( P = 0.53) and 12.0 versus 9.9 ( P = 0.89)]. The results were comparable when the biochemical disease activity definition was used. The mucosal concentrations and urinary excretion of (N-acetyl-)5-ASA did not differentiate between quiescent and active activity. CONCLUSIONS: Fecal (N-acetyl-)5-ASA measurements do not correlate with disease activity, which renders it an unsuitable tool for therapeutic drug monitoring of mesalazine.

Immunomodulator Withdrawal From Anti-TNF Therapy Is Not Associated With Loss of Response in Inflammatory Bowel Disease.

BACKGROUND AND AIMS: The benefit of concomitant immunomodulators (thiopurines or methotrexate) in patients with inflammatory bowel disease (IBD) on anti-tumor necrosis factor α (anti-TNF) (infliximab or adalimumab) maintenance therapy is debated. We compared outcomes after immunomodulator withdrawal vs continuation of combination therapy. METHODS: This was a retrospective cohort study in a general hospital and a tertiary referral center. We included adult IBD patients, receiving anti-TNF therapy for ≥4 months, plus an immunomodulator at baseline, between January 1, 2011, and January 1, 2019. The primary endpoints were loss of response (LOR) (ie, anti-TNF discontinuation because of disease activity) and anti-drug antibodies. Adjusted hazard ratios (aHRs) were calculated by mixed-effects Cox regression analysis. RESULTS: We included 614 treatment episodes of combination therapy in 543 individuals, yielding 1664 patient-years of follow-up. The immunomodulator was withdrawn in 296 (48.2%) episodes after 0.9 (interquartile range, 0.6-2.1) years, which was not associated with a higher risk of LOR (aHR, 1.08; 95% confidence interval [CI], 0.72-1.61), although anti-drug antibodies were detected more frequently (aHR, 2.14; 95% CI, 1.17-3.94), compared with continuation. Clinical remission at the time of withdrawal reduced the risk of LOR (aHR, 0.48; 95% CI, 0.25-0.93), while longer duration of combination therapy before withdrawal decreased the risk of anti-drug antibodies (HR per year, 0.56; 95% CI, 0.32-0.91). Higher prewithdrawal infliximab trough levels reduced the subsequent risks of anti-drug antibodies and LOR. Infliximab trough levels were lower after immunomodulator withdrawal (P = .01). CONCLUSIONS: Patients who withdrew the immunomodulator in this retrospective cohort were not at increased risk of LOR within the following 1-2 years, but an increase in anti-drug antibodies was observed. Our findings require prospective validation, preferably in adequately powered randomized controlled trials.

A Systematic Review With Meta-Analysis of the Efficacy of Cannabis and Cannabinoids for Inflammatory Bowel Disease: What Can We Learn From Randomized and Nonrandomized Studies?

GOAL AND BACKGROUND: A number of studies have investigated the effectiveness of cannabis or cannabinoids for treatment of inflammatory bowel diseases (IBD). We aimed to systematically analyze their effect in in the treatment of IBD patients. STUDY: We included randomized controlled trials and nonrandomized studies analyzing IBD patients of any age using cannabi(noid)s. Two reviewers searched 3 databases until August 13, 2019. Primary outcome was clinical remission and secondary outcomes included inflammatory biomarkers, symptom improvement, quality of life (QoL) scores, and hospital outcomes. Risk of bias was assessed according to study type. The meta-analyses were performed using a random-effects model with subgroup analyses based on study type. RESULTS: The search identified 682 records of which 15 nonrandomized studies and 5 randomized controlled trials were eligible for inclusion. The meta-analysis of the primary outcome included 146 randomized participants, all 18 years of age or older. Risk of bias was moderate. Cannabi(noid)s were not effective at inducing remission (risk ratio=1.56, 95% confidence interval=0.99-2.46). No effect on inflammatory biomarkers was observed. However, clinical symptoms (abdominal pain, general well-being, nausea, diarrhea, and poor appetite) all improved with cannabi(noid)s on Likert-scales. Baseline QoL scores were lower in patients using cannabis among cohort studies but improved significantly with cannabi(noid)s. Although length of hospital stay was shorter and risk of parenteral nutrition was lower in patients using cannabis, there was no effect on other IBD complications. CONCLUSIONS: Cannabi(noid)s do not induce clinical remission or affect inflammation in IBD patients. However, cannabi(noid)s significantly improve patient-reported symptoms and QoL.

Adherence to Adalimumab Was Not Improved by a Reminder-Based Intervention with an Electronic Needle Container.

BACKGROUND: Adherence to adalimumab in inflammatory bowel disease (IBD) patients is reported to be below par. Non-adherence may result in loss-of-response and increased hospitalization. We analyzed the effect of an electronic needle container (ENC) on adherence to adalimumab. METHODS: In this multicenter, 12-months observational study, we included adalimumab treated IBD patients. All patients were invited to receive an ENC. Patients who declined or did not complete the registration for an ENC served as controls. Primary endpoint was whether an ENC increased adherence, calculated from pharmacy refills as proportion of days covered (PDC). Secondary endpoints were clinical outcomes, including loss-of-response, identification of predictors of adherence and correlation between different modalities for measuring adherence. Loss-of-response was defined as a disease flare, dose-escalation or IBD-related hospitalization or surgery. RESULTS: The pharmacies' records identified 198 eligible patients, of whom 32 were excluded. The ENC was supplied to 69 patients, the remaining 97 patient formed the control group. Median baseline PDC (98.4% vs. 96.1%, p = 0.047) and the proportion of adherent (PDC ≥ 86%) patients (87.0% vs. 74.2%, p = 0.045) was higher for the ENC group. The ENC did not improve the adherence of patients during follow-up (odds ratio 1.26, 95% CI 0.55-2.86). During follow-up, five (7.2%) patients in the ENC group and 13 (13.4%) in the control group discontinued adalimumab (log-rank p = 0.22). Loss-of-response occurred in 12 (17.4%) and 14 (14.4%) patients, respectively (log-rank p = 0.66). CONCLUSIONS: Our results show no beneficial effect of a reminder-based intervention on adherence or treatment outcomes.

Anti-tumor necrosis factor therapy in patients with inflammatory bowel disease; comorbidity, not patient age, is a predictor of severe adverse events.

PURPOSE: To assess safety and effectiveness of anti-tumor necrosis factor (anti-TNF) therapy in IBD patients ≥ 60 years. METHODS: Ninety IBD patients ≥ 60 years at initiation of anti-TNF therapy, 145 IBD patients ≥ 60 years without anti-TNF therapy and 257 IBD patients < 60 years at initiation of anti-TNF therapy were retrospectively included in this multicentre study. Primary outcome was the occurrence of severe adverse events (SAEs), serious infections and malignancies. Secondary outcome was effectiveness of therapy. Cox regression analyses were used to assess differences in safety and effectiveness. In safety analyses, first older patients with and without anti-TNF therapy and then older and younger patients with anti-TNF therapy were assessed. RESULTS: In older IBD patients, the use of anti-TNF therapy was associated with serious infections (aHR 3.920, 95% CI 1.185-12.973, p = .025). In anti-TNF-exposed patients, cardiovascular disease associated with serious infections (aHR 3.279, 95% CI 1.098-9.790, p = .033) and the presence of multiple comorbidities (aHR 9.138 (1.248-66.935), p = .029) with malignancies, while patient age did not associate with safety outcomes. Effectiveness of therapy was not affected by age or comorbidity. CONCLUSION: Older patients receiving anti-TNF therapy have a higher risk of serious infections compared with older IBD patients without anti-TNF therapy, but not compared with younger patients receiving anti-TNF therapy. However, in anti-TNF-exposed patients, comorbidity was found to be an indicator with regards to SAEs. Effectiveness was comparable between older and younger patients.

Does the 5-Aminosalicylate Concentration Correlate with the Efficacy of Oral 5-Aminosalicylate and Predict Response in Patients with Inflammatory Bowel Disease? A Systematic Review.

BACKGROUND: Oral 5-aminosalicylic acid (5-ASA, mesalazine) is the first choice therapeutic agent for treating mild-to-moderate ulcerative colitis (UC). Unfortunately a significant group of patients fail to respond. Therapeutic drug monitoring might help to maintain or induce remission by providing a tool for optimization of 5-ASA therapy. However, plasma and urine concentrations of 5-ASA reflect systemic uptake and are not useful to evaluate therapeutic effect. OBJECTIVES: To explore if mucosal and faecal 5-ASA values correlate with disease activity and/or therapeutic effects in patients with inflammatory bowel disease, especially UC. METHOD: We identified studies that analysed 5-ASA in faeces or mucosa of humans using an oral 5-ASA formulation, using PubMed and Embase. RESULTS: In total, 39 studies (n = 939) were included, 27 on faecal 5-ASA, 9 on mucosal concentrations, and 3 on both faecal and mucosal values. We included 33 cross-sectional studies, 3 randomised clinical trials, 2 longitudinal cohorts and 1 randomized cross-over study. Mucosal 5-ASA concentrations in healthy subjects and patients on equivalent doses of 5-ASA were not found to differ remarkably. In the sub-analysis of mucosal 5-ASA concentrations in patients with active or quiescent UC, a higher concentration was seen during remission. Faecal concentrations were associated with 5-ASA doses but not with disease activity. Differences in faecal or mucosal 5-ASA values could not be ascribed to different 5-ASA formulations. CONCLUSIONS: An increase of the mucosal 5-ASA concentrations was observed during remission in patients with UC. No clear relationship between the faecal 5-ASA excretion and the therapeutic efficacy was identified.

Sexual Dysfunctions in Men and Women with Inflammatory Bowel Disease: The Influence of IBD-Related Clinical Factors and Depression on Sexual Function.

INTRODUCTION: Inflammatory bowel disease (IBD) is likely to have an impact on sexual function because of its symptoms, like diarrhea, fatigue, and abdominal pain. Depression is commonly reported in IBD and is also related to impaired sexual function. This study aimed to evaluate sexual function and its association with depression among patients with IBD compared with controls. METHODS: IBD patients registered at two hospitals participated. The control group consisted of a general practitioner practice population. The web-based questionnaire included the Female Sexual Function Index (FSFI) for women and the International Index of Erectile Function (IIEF) for men. Other variables evaluated were depression, disease activity, IBD-related quality of life, body image, and fatigue. RESULTS: In total, 168 female and 119 male patients were available for analysis (response rate 24%). Overall, patients with IBD did not significantly differ in prevalence of sexual dysfunctions from controls: female patients 52%, female controls 44%, male patients and male controls both 25%. However, men and women with an active disease scored significantly lower than patients in remission and controls, indicating impaired sexual functioning during disease activity. Significant associations were found between active disease, fatigue, depressive mood, quality of life, and sexual function for both male and female patients. The association between disease activity and sexual function was totally mediated by depression. CONCLUSION: Male and female IBD patients with an active disease show impaired sexual function relative to patients in remission and controls. Depression is the most important determinant for impaired sexual function in IBD.

Healthcare costs of inflammatory bowel disease have shifted from hospitalisation and surgery towards anti-TNFα therapy: results from the COIN study.

OBJECTIVE: The introduction of anti tumour necrosis factor-α (anti-TNFα) therapy might impact healthcare expenditures, but there are limited data regarding the costs of inflammatory bowel diseases (IBD) following the introduction of these drugs. We aimed to assess the healthcare costs and productivity losses in a large cohort of IBD patients. DESIGN: Crohn's disease (CD) and ulcerative colitis (UC) patients from seven university hospitals and seven general hospitals were invited to fill-out a web-based questionnaire. Cost items were derived from a 3 month follow-up questionnaire and categorised in outpatient clinic, diagnostics, medication, surgery and hospitalisation. Productivity losses included sick leave of paid and unpaid work. Costs were expressed as mean 3-month costs per patients with a 95% CI obtained using non-parametric bootstrapping. RESULTS: A total of 1315 CD patients and 937 UC patients were included. Healthcare costs were almost three times higher in CD as compared with UC, €1625 (95% CI €1476 to €1775) versus €595 (95% CI €505 to €685), respectively (p<0.01). Anti-TNFα use was the main costs driver, accounting for 64% and 31% of the total cost in CD and UC. Hospitalisation and surgery together accounted for 19% and <1% of the healthcare costs in CD and 23% and 1% in UC, respectively. Productivity losses accounted for 16% and 39% of the total costs in CD and UC. CONCLUSIONS: We showed that healthcare costs are mainly driven by medication costs, most importantly by anti-TNFα therapy. Hospitalisation and surgery accounted only for a minor part of the healthcare costs.

Optimizing screening for tuberculosis and hepatitis B prior to starting tumor necrosis factor-α inhibitors in Crohn's disease.

BACKGROUND AND AIMS: Treatment with tumor necrosis factor-α (TNF-α) inhibitors in patients with Crohn's disease (CD) is associated with potentially serious infections, including tuberculosis (TB) and hepatitis B virus (HBV). We assessed the cost-effectiveness of extensive TB screening and HBV screening prior to initiating TNF-α inhibitors in CD. METHODS: We constructed two Markov models: (1) comparing tuberculin skin test (TST) combined with chest X-ray (conventional TB screening) versus TST and chest X-ray followed by the interferon-gamma release assay (extensive TB screening) in diagnosing TB; and (2) HBV screening versus no HBV screening. Our base-case included an adult CD patient starting with infliximab treatment. Input parameters were extracted from the literature. Direct medical costs were assessed and discounted following a third-party payer perspective. The main outcome was the incremental cost-effectiveness ratio (ICER). Sensitivity and Monte Carlo analyses were performed over wide ranges of probability and cost estimates. RESULTS: At base-case, the ICERs of extensive screening and HBV screening were €64,340 and €75,760 respectively to gain one quality-adjusted life year. Sensitivity analyses concluded that extensive TB screening was a cost-effective strategy if the latent TB prevalence is more than 12 % or if the false positivity rate of TST is more than 20 %. HBV screening became cost-effective if HBV reactivation or HBV-related mortality is higher than 37 and 62 %, respectively. CONCLUSIONS: Extensive TB screening and HBV screening are not cost-effective compared with conventional TB screening and no HBV screening, respectively. However, when targeted at high-risk patient groups, these screening strategies are likely to become cost-effective.

Methotrexate accumulation in target intestinal mucosa and white blood cells differs from non-target red blood cells of patients with Crohn's disease.

BACKGROUND: Intracellular methotrexate polyglutamates (MTX-PGs) concentrations are measurable in red blood cells (RBCs) during MTX treatment. MTX-PG3 concentrations correlate with efficacy in patients with Crohn's disease (CD). Since RBCs are not involved in pathogenesis of CD and lack extended MTX metabolism, we determined MTX-PGs accumulation in peripheral blood mononuclear cells (PBMCs: effector cells) and intestinal mucosa (target cells) and compared those with RBCs as a potential more precise biomarker. METHODS: In a multicentre prospective cohort study, blood samples of patients with CD were collected during the first year of MTX therapy. Mucosal biopsies were obtained from non-inflamed rectum and/or inflamed intestine. MTX-PGs concentrations in mucosa, PBMCs and RBCs were measured by liquid chromatography-tandem mass spectrometry. RESULTS: From 80 patients with CD, a total of 27 mucosal biopsies, 9 PBMC and 212 RBC samples were collected. From 12 weeks of MTX therapy onwards, MTX-PG3 was the most predominant species (33%) in RBCs. In PBMCs, the distribution was skewed towards MTX-PG1 (48%), which accounted for an 18 times higher concentration than in RBCs. Long-chain MTX-PGs were highly present in mucosa: 21% of MTX-PGtotal was MTX-PG5. MTX-PG6 was measurable in all biopsies. CONCLUSIONS: MTX-PG patterns differ between mucosa, PBMCs and RBCs of patients with CD.

Limited predictive value of the gut microbiome and metabolome for response to biological therapy in inflammatory bowel disease.

Emerging evidence suggests the gut microbiome's potential in predicting response to biologic treatments in patients with inflammatory bowel disease (IBD). In this prospective study, we aimed to predict treatment response to vedolizumab and ustekinumab, integrating clinical data, gut microbiome profiles based on metagenomic sequencing, and untargeted fecal metabolomics. We aimed to identify predictive biomarkers and attempted to replicate microbiome-based signals from previous studies. We found that the predictive utility of the gut microbiome and fecal metabolites for treatment response was marginal compared to clinical features alone. Testing our identified microbial ratios in an external cohort reinforced the lack of predictive power of the microbiome. Additionally, we could not confirm previously published predictive signals observed in similar sized cohorts. Overall, these findings highlight the importance of external validation and larger sample sizes, to better understand the microbiome's impact on therapy outcomes in the setting of biologicals in IBD before potential clinical implementation.

Adalimumab and infliximab are equally effective for Crohn's disease in patients not previously treated with anti-tumor necrosis factor-α agents.

BACKGROUND & AIMS: Infliximab (IFX) and adalimumab (ADA) are thought to have equal efficacy for the treatment of Crohn's disease (CD), although no direct comparison has been performed. We compared the effectiveness and safety of IFX and ADA in carefully matched cohorts. METHODS: We performed a retrospective cohort study of 200 patients with CD (100 treated with IFX and 100 treated with ADA, starting in 2006 or later) who had not received anti-tumor necrosis factor α agents previously; the patients were identified from databases of 6 hospitals in The Netherlands. The groups were matched carefully for indication, duration of disease, age, and Montreal classification. The primary end point was the steroid-free clinical response, defined by a combination of multiple clinical parameters, after 1 year. RESULTS: Of the total patient population, 63.5% and 45% had a clinical response after 1 and 2 years, respectively. There were no significant differences between treatment groups: at 1 and 2 years, 62% and 41% of those receiving ADA vs 65% and 49% of those receiving IFX had responses, respectively. Kaplan-Meier curves showed identical decreases in response rates over time. Combining IFX or ADA with immunomodulator therapy was associated with a higher clinical response than monotherapy, although this was only significant among patients who received IFX (P = .03). There were no differences in numbers of side effects or opportunistic infections. CONCLUSIONS: The effectiveness of ADA or IFX treatment in anti-tumor necrosis factor α-naive patients with CD is comparable after 1 and 2 years of follow-up evaluation. The efficacies of IFX and ADA each seem to increase when given with immunomodulator therapy, although only significantly for IFX.

Adherence to microsatellite instability testing in young-onset colorectal cancer patients.

BACKGROUND: In 1997, the Bethesda guidelines recommended microsatellite instability testing for colorectal cancer in patients younger than 45 years to screen for Lynch syndrome. In 2004, these guidelines were revised to set the screening age at younger than 50 years. OBJECTIVE: The aim of this study was to investigate to what extent these guidelines were followed in young patients with colorectal cancer in the Mid-Netherlands and to identify the predictors of nonadherence. DESIGN: This is a retrospective cohort study. SETTINGS: This study was conducted in 1 academic and 5 nonacademic hospitals. PATIENTS: All patients diagnosed with colorectal cancer younger than 45 years in the period 1999 to 2004 and younger than 50 years in the period 2005 to 2008 were included. Patients known to be affected by or at risk for Lynch syndrome before diagnosis were excluded. MAIN OUTCOME MEASURES: Patient and tumor characteristics, including microsatellite instability testing results, were collected from the database of the Comprehensive Cancer Center, the National Pathological Archive, participating hospitals, and the regional institute of clinical genetics. Logistic regression analysis was performed to detect a trend in adherence over the years and to identify the predictors of nonadherence. RESULTS: A total of 335 patients were identified. Microsatellite instability testing was performed in 130/335 (39%) patients. Adherence did not improve in the period 1999 to 2008. We found that older age at diagnosis (OR 0.96, 95% CI 0.92-1.00), male sex (OR 0.60, 95% CI 0.38-0.95), and stage IV colorectal cancer (OR 0.45, 95% CI 0.24-0.84) were independent predictors of nonadherence, whereas proximal tumor localization, poor differentiation, and mucinous histology were not. LIMITATIONS: This study was limited by its retrospective design. CONCLUSIONS: Adherence to the Bethesda guidelines in young-onset colorectal cancer is low, particularly in older and male patients and in patients with metastatic disease, which suggests that efforts to improve adherence are needed.

Acute diverticulitis: a decade of prospective follow-up.

BACKGROUND: Acute diverticulitis (AD) is the most common complication of diverticular disease and affects 10% to 25% of patients. Data regarding the natural history of AD are lacking. GOALS: Our aim was to prospectively assess the occurrence of recurrent attacks, surgeries, and accompanying symptoms in patients who were hospitalized with AD. STUDY: All patients hospitalized with first episode of AD between January 2000 and November 2006 were enrolled. Patients were followed up both during hospitalization and after discharge. Data regarding operations and complications were collected. Special attention was paid to patients younger than 45 years of age and compared with older patients. RESULTS: A total of 261 patients were identified-of them 103 were men. Thirty patients (11.5%) were 45 years old or younger. The mean follow-up period was 88±22 months (range, 52 to 184 mo). Younger patients experienced significantly more complications during hospitalization (37% vs. 12.5%, P=0.001) and underwent more often a sigmoidectomy in the follow-up period (42.3% vs. 18.3%, P=0.01). Older patients tended to be more often asymptomatic after discharge (P=0.053). The average time from index hospitalization to the sigmoidectomy was 18.17±23.35 months (range, 1 to 120 mo). The odds ratio for sigmoidectomy after complicated AD is 16.2 (95% confidence interval, 13.4 to 19.6). Age did not affect the risk for surgery. CONCLUSIONS: Younger patients with AD experience more complications during hospitalization and undergo surgery after discharge more frequently. Complicated AD at index hospitalization is a risk factor for sigmoidectomy. Our data can help predict the outcome of patients suffering from AD and enable tailoring an individual treatment.

A rapid assay for on-site monitoring of infliximab trough levels: a feasibility study.

Monitoring levels of biologicals against tumor necrosis factor (TNF) has been suggested to improve therapeutic outcomes in inflammatory bowel diseases (IBDs). This pilot study describes a rapid lateral flow (LF)-based assay for on-site monitoring of serum trough levels of humanized monoclonal antibody infliximab (IFX). The applied chromatographic method utilizes sequential flows of diluted serum, wash buffer, and an immunoglobulin generic label on LF strips with a Test line comprised of TNF-α. The successive flows permitted enrichment of IFX at the Test line before the label was applied. The label, luminescent upconverting phosphor (UCP) particles coated with protein-A, emits a 550-nm visible light upon excitation with 980-nm infrared light. IFX concentrations were determined through measurement of UCP fluorescence at the Test line. The assay was optimized to detect IFX levels as low as 0.17 µg/mL in serum. For patients with IBD, this limit is appropriate to detect levels associated with loss of response (0.5 µg IFX/mL). The assay was evaluated with clinical samples from patients with Crohn's disease and correlated well within the physiologically relevant range from 0.17 to 10 µg/mL with an IFX-specific ELISA. Performance of the assay was further successfully validated with samples from blood donors, IFX negative IBD patients, and rheumatoid arthritis patients that had developed anti-IFX antibodies. Because of its generic nature, the assay is suited for detecting most therapeutic anti-TNF-α monoclonal antibodies.