Dynamic Prediction of Advanced Colorectal Neoplasia in Inflammatory Bowel Disease.

BACKGROUND & AIMS: Colonoscopic surveillance is recommended in patients with colonic inflammatory bowel disease (IBD) given their increased risk of colorectal cancer (CRC). We aimed to develop and validate a dynamic prediction model for the occurrence of advanced colorectal neoplasia (aCRN, including high-grade dysplasia and CRC) in IBD. METHODS: We pooled data from 6 existing cohort studies from Canada, The Netherlands, the United Kingdom, and the United States. Patients with IBD and an indication for CRC surveillance were included if they underwent at least 1 follow-up procedure. Exclusion criteria included prior aCRN, prior colectomy, or an unclear indication for surveillance. Predictor variables were selected based on the literature. A dynamic prediction model was developed using a landmarking approach based on Cox proportional hazard modeling. Model performance was assessed with Harrell's concordance-statistic (discrimination) and by calibration curves. Generalizability across surveillance cohorts was evaluated by internal-external cross-validation. RESULTS: The surveillance cohorts comprised 3731 patients, enrolled and followed-up in the time period from 1973 to 2021, with a median follow-up period of 5.7 years (26,336 patient-years of follow-up evaluation); 146 individuals were diagnosed with aCRN. The model contained 8 predictors, with a cross-validation median concordance statistic of 0.74 and 0.75 for a 5- and 10-year prediction window, respectively. Calibration plots showed good calibration. Internal-external cross-validation results showed medium discrimination and reasonable to good calibration. CONCLUSIONS: The new prediction model showed good discrimination and calibration, however, generalizability results varied. Future research should focus on formal external validation and relate predicted aCRN risks to surveillance intervals before clinical application.

Osteonecrosis in Inflammatory Bowel Disease: Clinical Features, Risk Factor Analysis, and Outcomes.

BACKGROUND: Avascular necrosis (AVN) is a known adverse event associated with corticosteroid (CS) usage. Inflammatory bowel disease (IBD) is often treated with a CS for induction of remission. We sought to describe clinical features and outcomes of IBD patients with AVN. METHODS: In this retrospective, single-center, case-control study, patients with IBD who had a diagnosis of osteonecrosis, aseptic necrosis, or AVN from 1976 to 2009 were included, and each was matched with up to 2 controls (IBD but no AVN) on age, sex, IBD subtype, geographic area of residence, and date of IBD diagnosis. We abstracted risk factor data from the medical records. Conditional logistic regression was performed accounting for minor differences in age and date of first IBD visit to assess the relationship between putative risk factors and AVN, expressed as odds ratio and 95% confidence interval. RESULTS: Eighty-five patients were diagnosed with IBD-AVN and were matched with 163 controls. The mean age at AVN diagnosis was 47.5 years. AVN was diagnosed a median of 12.2 years after IBD diagnosis, and the control group was followed for a median of 15 years after IBD diagnosis to ensure that they did not have AVN. Ten percent of patients with AVN did not have any CS exposure. History of arthropathy or estrogen use in Crohn's disease and use of CS, osteoporosis, and history of arthropathy in ulcerative colitis were significantly associated with AVN. CONCLUSIONS: Most patients with IBD-AVN had multifocal involvement. Most had received CS, but many patients had other risk factors including arthropathy.

This single-center, case-control study of inflammatory bowel disease patients with osteonecrosis showed that while corticosteroid use was likely a risk factor, especially among ulcerative colitis patients, other risk factors included estrogen use among Crohn's disease patients, arthropathy, and osteoporosis.

Early Cholangiocarcinoma Detection With Magnetic Resonance Imaging Versus Ultrasound in Primary Sclerosing Cholangitis.

BACKGROUND AND AIMS: Early detection of perihilar cholangiocarcinoma (CCA) among patients with primary sclerosing cholangitis (PSC) is important to identify more people eligible for curative therapy. While many recommend CCA screening, there are divergent opinions and limited data regarding the use of ultrasound or magnetic resonance imaging (MRI) for early CCA detection, and it is unknown whether there is benefit in testing asymptomatic individuals. Our aims were to assess the diagnostic performances and prognostic implications of ultrasound and MRI-based CCA detection. APPROACH AND RESULTS: This is a multicenter review of 266 adults with PSC (CCA, n = 120) who underwent both an ultrasound and MRI within 3 months. Images were re-examined by radiologists who were blinded to the clinical information. Respectively, MRI had a higher area under the curve compared with ultrasound for CCA detection: 0.87 versus 0.70 for the entire cohort; 0.81 versus 0.59 for asymptomatic individuals; and 0.88 versus 0.71 for those listed for CCA transplant protocol. The absence of symptoms at CCA diagnosis was associated with improved 5-year outcomes including overall survival (82% vs. 46%, log-rank P < 0.01) and recurrence-free survival following liver transplant (89% vs. 65%, log-rank P = 0.04). Among those with asymptomatic CCA, MRI detection (compared with ultrasound) was associated with reduction in both mortality (hazard ratio, 0.10; 95% confidence interval, 0.01-0.96) and CCA progression after transplant listing (hazard ratio, 0.10; 95% confidence interval, 0.01-0.90). These benefits continued among patients who had annual monitoring and PSC for more than 1 year before CCA was diagnosed. CONCLUSIONS: MRI is superior to ultrasound for the detection of early-stage CCA in patients with PSC. Identification of CCA before the onset of symptoms with MRI is associated with improved outcomes.

An update on primary sclerosing cholangitis epidemiology, outcomes and quantification of alkaline phosphatase variability in a population-based cohort.

BACKGROUND: Contemporary primary sclerosing cholangitis (PSC) population-based cohorts describing the epidemiology, natural history, and long-term fluctuations in serum alkaline phosphatase (SAP) and their prognostic relevance are lacking. Therefore, we investigated the incidence and natural history of PSC and quantified SAP fluctuations among those with PSC in Olmsted County, Minnesota over the last 41 years. METHODS: The Rochester Epidemiology Project was used to identify 56 subjects diagnosed with PSC between 1976 and 2017 in Olmsted County. The primary endpoint (n = 19) included liver transplantation, hepatic decompensation, and cholangiocarcinoma. RESULTS: The age- and sex-adjusted incidence of PSC (per 100,000 person years) nearly doubled from 2001 to 2017 compared to 1976-2000 (1.47; 95% CI 0.99-1.96 versus 0.79; 95% CI 0.42-1.16, p = 0.02). This increase paralleled a rise in patients with markers of a milder phenotype at the time of diagnosis: normal SAP (26.32% versus 0%, p < 0.01) and lower Mayo PSC risk score [0.36 (- 0.57 to 1.55) versus - 0.50 (- 1.25 to 0.35), p = 0.03]. Intra-individual SAP fluctuates with a median coefficient of variation of 36.20%. SAP normalization and dropping below 1.5 × upper limit of normal (ULN) occurs at a rate of 5% and 10% per year, respectively. SAP less than 1.5 × ULN was associated with a lower risk of PSC-related complications (hazard ratio 0.11; 95% CI 0.03-0.42). CONCLUSIONS: The patients with PSC are increasingly being diagnosed with a milder phenotype. While a lower SAP is associated with improved outcomes, the high intra-individual variation of SAP levels calls into question the practice of using a single SAP value as a surrogate endpoint in clinical trials.

Comparison of liver stiffness measurement with MRE and liver and spleen volumetry for prediction of disease severity and hepatic decompensation in patients with primary sclerosing cholangitis.

PURPOSE: To compare liver stiffness measurement (LSM) with magnetic resonance elastography (MRE) and liver and spleen volumetry for prediction of disease severity and hepatic decompensation in primary sclerosing cholangitis (PSC). METHODS: This retrospective study was approved by the institutional review board. Magnetic resonance imaging (MRI) and MRE studies were reviewed, and mean LSM of entire liver, right lobe and left lobe, total liver, right lobe, left lobe, caudate lobe, and spleen volumes were calculated. Qualitative evaluation of lobar atrophy or hypertrophy and presence of macronodular regeneration (MNR) was recorded. Statistical analysis was performed to evaluate correlations between LSM, volumetry measurements, and Mayo risk score. Univariate and multivariate analyses were performed to predict hepatic decompensation. RESULTS: A total of 266 patients with PSC were included in the study. Lobar stiffness measures were higher in the presence of relative lobe atrophy. Mean LSM was higher in the presence of MNR. Significant correlations were observed between mean LSM and volumetry measurements with a fair correlation between LSM and spleen volume (rs = 0.526, p < 0.0001). Among the measurements, the best correlation was observed between mean LSM and Mayo risk score (rs = 0.646, p < 0.0001). In the multivariate analyses, mean LSM and Mayo risk score were significantly associated with liver decompensation (hazard ratio, 1.18; 95%CI 1.02-1.36 and hazard ratio, 1.65; 95%CI 1.08-2.53, respectively). CONCLUSION: LSM with MRE performs significantly better than liver and spleen volumes for prediction of both disease severity and hepatic decompensation.

Incidence and Outcomes of Home Parenteral Nutrition in Patients With Crohn Disease in Olmsted County, Minnesota.

BACKGROUND: We sought to estimate the incidence of home parenteral nutrition (HPN) use in a population-based cohort of patients with Crohn disease (CD), and to assess clinical outcomes and complications associated with HPN. METHODS: We used the Rochester Epidemiology Project (REP) to identify residents of Olmsted County, who were diagnosed with CD between 1970 and 2011, and required HPN. RESULTS: Fourteen out of 429 patients (3.3%) with CD received HPN (86% female). Eleven patients (79%) had moderate-severe CD and 12 patients (86%) had fistulizing disease. Thirteen patients (93%) underwent surgery, primarily due to obstruction. Among CD incidence cases, the cumulative incidence of HPN from the date of CD diagnosis was 0% at 1 year, 0.5% at 5 years, 0.8% at 10 years, and 2.4% at 20 years. Indications for HPN included short bowel syndrome in 64%, malnutrition in 29%, and bowel rest in 21%. The median duration of HPN was 2.5 years. There was an average weight gain of 1.2 kg at 6 months, an average weight loss of 1.4 kg at 1 year, and a further weight loss of 2.2 kg at 2 years from the start of HPN. Patients were hospitalized a mean of 5 times after the start of HPN, mainly due to catheter-related bloodstream infections and thrombosis. CONCLUSIONS: Less than 4% of patients with CD need HPN. Most have moderate to severe disease with short bowel syndrome or malnutrition. Possible reasons for the patients' weight loss could be noncompliance, and increased metabolic needs because of active disease.

Effects of Clarithromycin-Containing Quadruple Therapy on Helicobacter Pylori Eradication after Nitroimidazole-Containing Quadruple Therapy Failure.

BACKGROUND Several large clinical trials and meta-analyses have shown about 20% failure to eradicate Helicobacter pylori (H.pylori), necessitating investigations for second-line treatments. The aim of this study was to evaluate the effects of clarithromycin-containing quadruple regimen after nitroimidazole-containing quadruple therapy failure. METHODS Thirty two patients who had failed 10-day H.pylori treatment with omeprazole, amoxicillin, bismuth subcitrate, and metronidazole (OABM) regimen and 31 patients who had failed 10-day treatment with omeprazole, amoxicillin, bismuth subcitrate, and furazolidone (OAMF) regimen entered the study. They all received omeprazole (20 mg), amoxicillin (1 gr), bismuth subcitrate (240 mg) and clarithromycin (500 mg) twice a day for 10 days. Eight weeks after treatment, H. pylori eradication was assessed by (14)C-urea breath test. RESULTS Totally 61 patients completed the study. According to intention to treat (ITT) analysis, eradication rates by second-line OABC regimen were 84.37% (95% CI= 71.7-96.9%) in OABM group and 77.41% (95% CI= 62.71-92.11%) in OABF group (p=0.756). Per-protocol (pp) eradication rates were 87.09% (95% CI= 75.2-98.8%) and 82.75% (95% CI= 79.4-96%), respectively (p=0.638). Also the cumulative eradication rates by OABC regimen were 80.9% (95% CI= 71.2-90.6%) and 85% (95% CI= 75.9-94%) according to ITT and PP analyses, respectively. Severe side effects were reported in 3.1% of the patients. CONCLUSION Regarding ideal eradication rate (>80%) and very low adverse effects, it seems that clarithromycin-containing quadruple therapy can be an encouraging regimen after nitroimidazole-containing regimen failure.

Growth kinetic models for phenol biodegradation in a batch culture of Pseudomonas putida.

Biodegradation of phenol with pure culture of Pseudomonas putida was investigated. P. putida (PTCC 1694) was grown in facultative anaerobic condition at 27 degrees C and media pH value of 7. The effect of initial phenol concentration on the biodegradation rate was studied. The initial concentrations of phenol varied from 300 to 1000 mg/l. Experiments were performed for the duration of seven days while daily samples were withdrawn. The initial rate of biodegradation of phenol increased with initial concentration of 300-500 mg/l. Further increase in phenol concentration resulted in a slight decrease in the rate of biodegradation due to phenol inhibition. It was observed that by increasing the concentration of phenol, the lag phase was prolonged. Phenol is known to be an inhibitory substrate, thus Monod, Haldane and logistic kinetic models were applied to evaluate the growth kinetic parameters. The Monod model was unable to present the growth parameters over the defined concentration range. However, Haldane and logistic models perfectly fitted with the experimental data. The yield coefficients for the growth on phenol at concentrations of 300, 500, 700 and 1000 mg/l were 0.177, 0.062, 0.035 and 0.012 mg/mg, respectively.