Comparison between 16S rRNA and shotgun sequencing in colorectal cancer, advanced colorectal lesions, and healthy human gut microbiota.

BACKGROUND: Gut dysbiosis has been associated with colorectal cancer (CRC), the third most prevalent cancer in the world. This study compares microbiota taxonomic and abundance results obtained by 16S rRNA gene sequencing (16S) and whole shotgun metagenomic sequencing to investigate their reliability for bacteria profiling. The experimental design included 156 human stool samples from healthy controls, advanced (high-risk) colorectal lesion patients (HRL), and CRC cases, with each sample sequenced using both 16S and shotgun methods. We thoroughly compared both sequencing technologies at the species, genus, and family annotation levels, the abundance differences in these taxa, sparsity, alpha and beta diversities, ability to train prediction models, and the similarity of the microbial signature derived from these models. RESULTS: As expected, the results showed that 16S detects only part of the gut microbiota community revealed by shotgun, although some genera were only profiled by 16S. The 16S abundance data was sparser and exhibited lower alpha diversity. In lower taxonomic ranks, shotgun and 16S highly differed, partially due to a disagreement in reference databases. When considering only shared taxa, the abundance was positively correlated between the two strategies. We also found a moderate correlation between the shotgun and 16S alpha-diversity measures, as well as their PCoAs. Regarding the machine learning models, only some of the shotgun models showed some degree of predictive power in an independent test set, but we could not demonstrate a clear superiority of one technology over the other. Microbial signatures from both sequencing techniques revealed taxa previously associated with CRC development, e.g., Parvimonas micra. CONCLUSIONS: Shotgun and 16S sequencing provide two different lenses to examine microbial communities. While we have demonstrated that they can unravel common patterns (including microbial signatures), shotgun often gives a more detailed snapshot than 16S, both in depth and breadth. Instead, 16S will tend to show only part of the picture, giving greater weight to dominant bacteria in a sample. Therefore, we recommend choosing one or another sequencing technique before launching a study. Specifically, shotgun sequencing is preferred for stool microbiome samples and in-depth analyses, while 16S is more suitable for tissue samples and studies with targeted aims.

Performance of a Shotgun Prediction Model for Colorectal Cancer When Using 16S rRNA Sequencing Data.

Colorectal cancer (CRC), the third most common cancer globally, has shown links to disturbed gut microbiota. While significant efforts have been made to establish a microbial signature indicative of CRC using shotgun metagenomic sequencing, the challenge lies in validating this signature with 16S ribosomal RNA (16S) gene sequencing. The primary obstacle is reconciling the differing outputs of these two methodologies, which often lead to divergent statistical models and conclusions. In this study, we introduce an algorithm designed to bridge this gap by mapping shotgun-derived taxa to their 16S counterparts. This mapping enables us to assess the predictive performance of a shotgun-based microbiome signature using 16S data. Our results demonstrate a reduction in performance when applying the 16S-mapped taxa in the shotgun prediction model, though it retains statistical significance. This suggests that while an exact match between shotgun and 16S data may not yet be feasible, our approach provides a viable method for comparative analysis and validation in the context of CRC-associated microbiome research.

Quality of Colonoscopy Is Associated With Adenoma Detection and Postcolonoscopy Colorectal Cancer Prevention in Lynch Syndrome.

BACKGROUND & AIMS: Colonoscopy reduces colorectal cancer (CRC) incidence and mortality in Lynch syndrome (LS) carriers. However, a high incidence of postcolonoscopy CRC (PCCRC) has been reported. Colonoscopy is highly dependent on endoscopist skill and is subject to quality variability. We aimed to evaluate the impact of key colonoscopy quality indicators on adenoma detection and prevention of PCCRC in LS. METHODS: We conducted a multicenter study focused on LS carriers without previous CRC undergoing colonoscopy surveillance (n = 893). Incident colorectal neoplasia during surveillance and quality indicators of all colonoscopies were analyzed. We performed an emulated target trial comparing the results from the first and second surveillance colonoscopies to assess the effect of colonoscopy quality indicators on adenoma detection and PCCRC incidence. Risk analyses were conducted using a multivariable logistic regression model. RESULTS: The 10-year cumulative incidence of adenoma and PCCRC was 60.6% (95% CI, 55.5%-65.2%) and 7.9% (95% CI, 5.2%-10.6%), respectively. Adequate bowel preparation (odds ratio [OR], 2.07; 95% CI, 1.06-4.3), complete colonoscopies (20% vs 0%; P = .01), and pan-chromoendoscopy use (OR, 2.14; 95% CI, 1.15-3.95) were associated with significant improvement in adenoma detection. PCCRC risk was significantly lower when colonoscopies were performed during a time interval of less than every 3 years (OR, 0.35; 95% CI, 0.14-0.97). We observed a consistent but not significant reduction in PCCRC risk for a previous complete examination (OR, 0.16; 95% CI, 0.03-1.28), adequate bowel preparation (OR, 0.64; 95% CI, 0.17-3.24), or previous use of high-definition colonoscopy (OR, 0.37; 95% CI, 0.02-2.33). CONCLUSIONS: Complete colonoscopies with adequate bowel preparation and chromoendoscopy use are associated with improved adenoma detection, while surveillance intervals of less than 3 years are associated with a reduction of PCCRC incidence. In LS, high-quality colonoscopy surveillance is of utmost importance for CRC prevention.

The EPAGE guidelines are not an effective strategy for managing colonoscopies during the COVID-19 pandemic. / EPAGE no es una estrategia eficaz para la gestión de colonoscopias durante la pandemia por COVID-19.

INTRODUCTION: The pandemic caused by the SARS-CoV-2 virus has had a serious impact on the functioning of gastrointestinal endoscopy Units. The Asociación Española de Gastroenterología (AEG) and the Sociedad Española de Endoscopia Digestiva (SEED) have proposed the EPAGE guidelines for managing postponed colonoscopies. OBJECTIVE: To evaluate the EPAGE guidelines as a management tool compared to the immunologic faecal occult blood test (iFOBT) and compared to risk score (RS) that combines age, sex and the iFOBT for the detection of colorectal cancer (CRC) and significant bowel disease (SBD). METHODS: A prospective, single-centre study enrolling 743 symptomatic patients referred for a diagnostic colonoscopy. Each order was classified according to the EPAGE guidelines as appropriate, indeterminate or inappropriate. Patients underwent an iFOBT and had their RS calculated. RESULTS: The iFOBT (p<0.001), but not the EPAGE guidelines (p = 0.742), was an independent predictive factor of risk of CRC. The ROC AUCs for the EPAGE guidelines, the iFOBT and the RS were 0.61 (95% CI 0.49-0.75), 0.95 (0.93-0.97) and 0.90 (0.87-0.93) for CRC, and 0.55 (0.49-0.61), 0.75 (0.69-0.813) and 0.78 (0.73-0.83) for SBD, respectively. The numbers of colonoscopies needed to detect a case of CRC and a case of SBD were 38 and seven for the EPAGE guidelines, seven and two for the iFOBT, and 19 and four for a RS ≥5 points, respectively. CONCLUSION: The EPAGE guidelines, unlike the iFOBT, is not suitable for screening candidate patients for a diagnostic colonoscopy to detect CRC. The iFOBT, in combination with age and sex, is the most suitable strategy for managing demand for endoscopy in a restricted-access situation.

Polygenic risk score across distinct colorectal cancer screening outcomes: from premalignant polyps to colorectal cancer.

BACKGROUND: Different risk-based colorectal cancer (CRC) screening strategies, such as the use of polygenic risk scores (PRS), have been evaluated to improve effectiveness of these programs. However, few studies have previously assessed its usefulness in a fecal immunochemical test (FIT)-based screening study. METHODS: A PRS of 133 single nucleotide polymorphisms was assessed for 3619 participants: population controls, screening controls, low-risk lesions (LRL), intermediate-risk (IRL), high-risk (HRL), CRC screening program cases, and clinically diagnosed CRC cases. The PRS was compared between the subset of cases (n = 648; IRL+HRL+CRC) and controls (n = 956; controls+LRL) recruited within a FIT-based screening program. Positive predictive values (PPV), negative predictive values (NPV), and the area under the receiver operating characteristic curve (aROC) were estimated using cross-validation. RESULTS: The overall PRS range was 110-156. PRS values increased along the CRC tumorigenesis pathway (Mann-Kendall P value 0.007). Within the screening subset, the PRS ranged 110-151 and was associated with higher risk-lesions and CRC risk (ORD10vsD1 1.92, 95% CI 1.22-3.03). The cross-validated aROC of the PRS for cases and controls was 0.56 (95% CI 0.53-0.59). Discrimination was equal when restricted to positive FIT (aROC 0.56), but lower among negative FIT (aROC 0.55). The overall PPV among positive FIT was 0.48. PPV were dependent on the number of risk alleles for positive FIT (PPVp10-p90 0.48-0.57). CONCLUSIONS: PRS plays an important role along the CRC tumorigenesis pathway; however, in practice, its utility to stratify the general population or as a second test after a FIT positive result is still doubtful. Currently, PRS is not able to safely stratify the general population since the improvement on PPV values is scarce.

Bayes-based dosing of infliximab in inflammatory bowel diseases: Short-term efficacy.

AIMS: Therapeutic drug monitoring of infliximab can guide clinical decisions in patients with loss of response and in those who can benefit from a de-intensification. The aim of this study was to determine the impact of therapeutic drug monitoring combined with Bayesian forecasting methodology on clinical response in a real-world dataset of patients suffering from inflammatory bowel disease. METHODS: We performed a single-centre prospective study with one-group pre-test/post-test design in 108 adult inflammatory bowel disease patients treated with model-based dosing of infliximab maintenance treatment. We recorded clinical activity scores (Harvey-Bradshaw index and partial Mayo) and inflammatory biomarkers per patient. RESULTS: The initial infliximab regimen was maintained in 49 (45.4%) patients and was adjusted in 59 (54.6%) patients (34 treatment intensifications, 9 de-intensifications and 16 treatment discontinuations or therapy replacements). The median time from intervention to index measurement was 126 (103-160) days. The overall proportion of patients in clinical remission increased from 65.7% to 80.4% (P < .0001) and the median infliximab trough concentrations increased from 3.21 (0.99-5.45) to 5.13 mg/L (3.57-6.53) (P < .0001). In the intensified group, the remission rate increased from 35.3% to 61.8% (P = .001) and the percentage of patients in clinical remission or with mild symptoms increased from 76.5% to 94.1%. In the de-intensification cohort, no patients experienced an increase in the Harvey-Bradshaw index or partial Mayo scores, and all patients maintained an infliximab trough concentration of >5 mg/L. CONCLUSION: In our cohort of inflammatory bowel disease patients, Bayes-based optimized dosing improved the short-term efficacy of infliximab treatment.

Predictors of Infliximab Trough Concentrations in Inflammatory Bowel Disease Patients Using a Repeated-Measures Design.

BACKGROUND AND AIMS: Treating patients based on a treat-to-trough approach has been shown to be a cost-effective strategy for inflammatory bowel disease (IBD) patients who have become unresponsive to infliximab (IFX). However, the documented evidence for this is limited, and some controversy remains regarding the use of routine proactive therapeutic drug monitoring (TDM). To support routine TDM of IFX and regimen optimization in IBD patients, more in-depth knowledge of the covariates that affect the pharmacokinetic (PK) variability of IFX is needed. The aim of this study was to identify the characteristics of the patient, disease, and treatments that influence IFX PK and exposure in our cohort of IBD patients using a repeated-measures design. METHODS: We performed a prospective observational study of adult IBD patients who received IFX between July 2013 and March 2017. We obtained repeated IFX trough concentration (Cmin) measurements and implemented a previously described population pharmacokinetic model to estimate individual clearance (CL). From the individual primary parameters, the area under the curve (AUC), half-life (t1/2), and central elimination rate constant (K10) were estimated. We performed a repeated-measures analysis to evaluate whether patient characteristics, disease status, concomitant immunosuppressive therapy, and immunogenicity are associated with IFX Cmin and PK parameters. RESULTS: We collected 429 Cmin measurements from 112 patients. The median of the Cmin values was 3.62 mg/L (1.47-6.02). Antibodies to IFX (ATI) were detected in 14 patients. The predicted median AUC was 28,421 mg/h/L (22,336-36,903). The median individual predicted CL, K10, and t1/2 values were 4.77 mL/kg/day (3.88-5.90), 0.09 days (0.08-0.12), and 12.22 days (9.49-14.87), respectively. IFX Cmin, AUC, CL, and K10 were significantly influenced by ATI and serum albumin concentrations. Moreover, body weight was significantly associated with AUC, CL, and K10. Patients receiving concurrent immunosuppressive therapy had higher Cmin and AUC values and lower CL and K10 values than those treated with IFX monotherapy. We also observed high intrapatient variability in Cmin values during the study period. CONCLUSIONS: In this repeated-measures study in a population of IBD patients, we observed significant associations between ATI, serum albumin concentration, concomitant immunosuppressive therapy, body weight and gender, and IFX Cmin, and CL. The high PK variability observed in this study supports the need for proactive TDM to optimize the use of IFX as early as possible in IBD patients.

The use of faecal immunochemical testing in the decision-making process for the endoscopic investigation of iron deficiency anaemia.

Background Blood loss from the gastrointestinal (GI) tract is the most common cause of iron deficiency anaemia (IDA) in adult men and postmenopausal women. Gastroduodenal endoscopy (GDE) and colonoscopy are frequently recommended, despite uncertainty regarding the coexistence of lesions in the upper and lower GI tract. The faecal immunochemical test (FIT) measures the concentration of faecal haemoglobin (f-Hb) originating only from the colon or rectum. We aimed to assess whether the FIT was able to select the best endoscopic procedure for detecting the cause of IDA. Methods A prospective study of 120 men and postmenopausal women referred for a diagnostic study of IDA were evaluated with an FIT, GDE and colonoscopy. The endoscopic finding of a significant upper lesion (SUL) or a significant bowel lesion (SBL) was considered to be the cause of the IDA. Results The diagnoses were 35.0% SUL and 20.0% SBL, including 13.3% GI cancer. In the multivariate analysis, the concentration of blood haemoglobin (b-Hb) <9 g/dL (OR: 2.60; 95% CI 1.13-6.00; p = 0.025) and non-steroidal anti-inflammatory drugs NSAIDs (2.56; 1.13-5.88; p = 0.024) were associated with an SUL. Age (0.93; 0.88-0.99; p = 0.042) and f-Hb ≥ 15 µg Hb/g faeces (38.53; 8.60-172.50; p < 0.001) were associated with an SBL. A "FIT plus gastroscopy" strategy, in which colonoscopy is performed only when f-Hb ≥15 µg Hb/g faeces, would be able to detect 92.4% of lesions and be 100% accurate in the detection of cancer while avoiding 71.6% of colonoscopies. Conclusions The FIT is an accurate method for selecting the best endoscopy study for the evaluation of IDA. An FIT-based strategy is more cost-effective than the current bidirectional endoscopy-based strategy and could improve endoscopic resource allocation.

High incidence of advanced colorectal neoplasia during endoscopic surveillance in serrated polyposis syndrome.

BACKGROUND: Serrated polyposis syndrome (SPS) has been associated with an increased risk of colorectal cancer (CRC). Accordingly, intensive surveillance with annual colonoscopy is advised. The aim of this multicenter study was to describe the risk of advanced lesions in SPS patients undergoing surveillance, and to identify risk factors that could guide the prevention strategy. METHODS: From March 2013 to April 2015, 296 patients who fulfilled criteria I and/or III for SPS were retrospectively recruited at 18 centers. We selected patients in whom successful clearing colonoscopy had been performed and who underwent subsequent endoscopic surveillance. Advanced neoplasia was defined as CRC, advanced adenoma, or advanced serrated lesion that were ≥ 10 mm and/or with dysplasia. Cumulative incidence of advanced neoplasia was calculated and independent predictors of advanced neoplasia development were identified. RESULTS: In 152 SPS patients a total of 315 surveillance colonoscopies were performed (median 2, range 1 - 7). The 3-year cumulative incidence of CRC and advanced neoplasia were 3.1 % (95 % confidence interval [CI] 0 - 6.9) and 42.0 % (95 %CI 32.4 - 51.7), respectively. Fulfilling both I + III criteria and the presence of advanced serrated lesions at baseline colonoscopy were independent predictors of advanced neoplasia development (odds ratio [OR] 1.85, 95 %CI 1.03 - 3.33, P  = 0.04 and OR 2.62, 95 %CI 1.18 - 5.81, P  = 0.02, respectively). During follow-up, nine patients (5.9 %) were referred for surgery for invasive CRC (n = 4, 2.6 %) or because of polyp burden (n = 5, 3.3 %). After total colectomy, 17.9 % patients developed advanced neoplasia in the retained rectum. CONCLUSIONS: Patients with SPS have a substantial risk of developing advanced neoplasia under endoscopic surveillance, whereas CRC incidence is low. Personalized endoscopic surveillance based on polyp burden and advanced serrated histology could help to optimize prevention in patients with SPS.

External Evaluation of Population Pharmacokinetic Models of Infliximab in Patients With Inflammatory Bowel Disease.

BACKGROUND: Infliximab (IFX) trough levels vary markedly between patients with inflammatory bowel disease (IBD), which is important for clinical response. The aim of this study was to evaluate the performance of previously developed population pharmacokinetic models in patients with IBD for dose individualization for Crohn disease (CD) and ulcerative colitis in our clinical setting. METHODS: The authors collected 370 trough levels prospectively from 100 adult patients with IBD who were undergoing IFX treatment between July 2013 and August 2016. The external evaluation included prediction- and simulation-based diagnostics [prediction-corrected visual predictive check, prediction- and variability-corrected visual predictive check, and normalized prediction distribution error tests]. RESULTS: In prediction-based diagnostics, the authors observed a nonsignificant overall mean relative bias of -6.87% and an acceptable imprecision of 8.45%. Approximately 100% of the prediction error was within ±30%, indicating satisfactory predictability. Simulation-based diagnostics indicated model misspecification; thus, the model may not be appropriate for simulation-based applications. CONCLUSIONS: While simulation-based diagnostics provided unsatisfactory results, the prediction-based diagnostics demonstrate that the population pharmacokinetic model developed by Fasanmade et al for CD can be used to predict and design individualized IFX dose regimens that meet the individual needs of patients with CD and ulcerative colitis.

The fecal hemoglobin concentration, age and sex test score: Development and external validation of a simple prediction tool for colorectal cancer detection in symptomatic patients.

Prediction models for colorectal cancer (CRC) detection in symptomatic patients, based on easily obtainable variables such as fecal haemoglobin concentration (f-Hb), age and sex, may simplify CRC diagnosis. We developed, and then externally validated, a multivariable prediction model, the FAST Score, with data from five diagnostic test accuracy studies that evaluated quantitative fecal immunochemical tests in symptomatic patients referred for colonoscopy. The diagnostic accuracy of the Score in derivation and validation cohorts was compared statistically with the area under the curve (AUC) and the Chi-square test. 1,572 and 3,976 patients were examined in these cohorts, respectively. For CRC, the odds ratio (OR) of the variables included in the Score were: age (years): 1.03 (95% confidence intervals (CI): 1.02-1.05), male sex: 1.6 (95% CI: 1.1-2.3) and f-Hb (0-<20 µg Hb/g feces): 2.0 (95% CI: 0.7-5.5), (20-<200 µg Hb/g): 16.8 (95% CI: 6.6-42.0), ≥200 µg Hb/g: 65.7 (95% CI: 26.3-164.1). The AUC for CRC detection was 0.88 (95% CI: 0.85-0.90) in the derivation and 0.91 (95% CI: 0.90-093; p = 0.005) in the validation cohort. At the two Score thresholds with 90% (4.50) and 99% (2.12) sensitivity for CRC, the Score had equivalent sensitivity, although the specificity was higher in the validation cohort (p < 0.001). Accordingly, the validation cohort was divided into three groups: high (21.4% of the cohort, positive predictive value-PPV: 21.7%), intermediate (59.8%, PPV: 0.9%) and low (18.8%, PPV: 0.0%) risk for CRC. The FAST Score is an easy to calculate prediction tool, highly accurate for CRC detection in symptomatic patients.

Spontaneous intramural esophageal dissection: an unusual onset of eosinophilic esophagitis.

A 35-year-old man, with a history of rhinitis, eczema and a dubious achalasia was admitted due to chest pain and sialorrhea. Upper endoscopy showed a little hole and a narrowing of the distal esophagus. A CT-scan with oral contrast exposed a discontinuity of the lumen of the middle third of the esophagus and a dissection of submucosal space 16 cm long. The patient recovered after parenteral nutrition. After four months, an esophageal endoscopic showed transient whitish exudates, longitudinal furrows and esophageal lacerations. The biopsies illustrated significant eosinophilic inflammation, eosinophilic microabscesses and basal cell hyperplasia.

Fecal level of calprotectin identifies histologic inflammation in patients with ulcerative colitis in clinical and endoscopic remission.

BACKGROUND & AIMS: Histologic recovery of patients with ulcerative colitis (UC) often is incomplete, even among those in clinical and endoscopic remission. Persistent active microscopic inflammation is associated with an increased risk of relapse and colorectal neoplasia. A high level of fecal calprotectin (FC) is a reliable marker of endoscopic lesions in patients with UC. We evaluated the accuracy of FC in identifying patients with UC in clinical and endoscopic remission who still have histologic features of inflammation. METHODS: We performed a prospective observational study of 59 patients with UC in clinical and endoscopic remission undergoing colonoscopy. Several biopsy specimens were collected from each colonic segment. Endoscopic remission was defined as a Mayo endoscopic subscore with a grade of 0 or 1. Active histologic inflammation was defined by the presence of neutrophils infiltrating crypt epithelial cells. FC was determined by enzyme-linked immunosorbent assay analysis. RESULTS: Eighteen patients (30.5%) showed evidence of active histologic inflammation. Patients with active histologic inflammation had a significantly higher median level of FC (278 µg/g; interquartile range, 136-696 µg/g) than those without active histologic inflammation (68 µg/g; interquartile range, 30-172 µg/g) (P = .002). In multivariate analysis, the FC and Mayo endoscopic subscore (0 or 1) were each independent predictors of histologic inflammation. The level of FC identified active histologic inflammation in patients in clinical and endoscopic remission, with an area under the receiver operator characteristic curve value of 0.754. CONCLUSIONS: Histologic inflammation is common among patients with UC in clinical and endoscopic remission. Patients with histologic features of inflammation can be identified reliably based on their fecal level of calprotectin.

[Approach to the diagnosis and treatment of chronic anemia secondary to gastrointestinal diseases]. / Aproximación al diagnostic y tratamiento de la anemia crónica secundaria a causas digestivas.

Iron deficiency anemia is the most common type of anemia and can cause asthenia, cognitive and functional impairment, and decompensation of underlying diseases. Iron deficiency anemia is not a disease but is the result of a potentially serious medical problem. Consequently, patients should always undergo investigation of the underlying cause. In men and postmenopausal women, the condition is caused by gastrointestinal loss and malabsorption of iron. In this group, recommended procedures are gastroscopy, colonoscopy and serological testing for celiac disease. If the results of these tests are negative, repeat examinations and iron therapy should be considered. In treatment-refractory or recurrent anemia, the small intestine should be investigated. In this case, the procedure of choice is capsule endoscopy. Iron deficiency anemia should always be treated until iron deposits have returned to normal levels. A wide variety of preparations are available, in both oral and parental formulations.

[Fecal calprotectin in the diagnosis of inflammatory bowel diseases]. / Calprotectina fecal en el diagnóstico de enfermedades inflamatorias.

The diagnosis of inflammatory bowel diseases has classically been based on assessment of digestive symptoms. The development of these symptoms usually results in colonoscopy, which has a low diagnostic yield. Likewise, there is an increasing tendency to base treatment of inflammatory bowel disease on objective data, since the disappearance of signs of activity on colonoscopy (called « mucosal cure ¼) has been associated with sustained clinical remission and reduced rates of hospitalization and surgery. Consequently, there is a need for biomarkers that would aid the selection of those patients who would derive most benefit from an endoscopic examination. One substance that has been proposed as a biomarker of bowel inflammation is fecal calprotectin. This substance allows inflammatory bowel disease to be distinguished from irritable bowel syndrome and shows a better correlation with the degree of inflammation than clinical indicators and serological markers. In addition, it could also be useful to predict mucosal cure and the risk of recurrence.

Validation of screening criteria for spondyloarthritis in patients with inflammatory bowel disease in routine clinical practice.

BACKGROUND: Spondyloarthritis (SpA) is one of the most common extraintestinal manifestations of inflammatory bowel disease (IBD). Diagnostic delay must be avoided. AIMS: We assessed the validity of SpA screening criteria (any of the following characteristics: chronic low back pain with onset before 45 years of age; inflammatory lower back pain or alternating buttock pain; arthritis; heel enthesitis; dacylitis; HLA-B27 positivity; sacroiliitis on imaging). METHODS: This was a multicenter cross-sectional observational study in IBD patients aged ≥18 years. After evaluating the SpA screening criteria, the gastroenterologists referred the participants to the rheumatologists, who determined whether the patient fulfilled the screening criteria and carried out the necessary tests for SpA diagnosis. RESULTS: 35 (11.7%) out of 300 patients were diagnosed with SpA. The combination with the best balance between sensitivity and specificity (91.4% and 72.1%, respectively, when applied by the rheumatologists; 80% and 78.9%, when applied by the gastroenterologists) for SpA screening, was fulfillment of any of the following: chronic low back pain with onset before age 45 years, inflammatory low back pain or alternating buttock pain, arthritis, or dactylitis. CONCLUSION: This is one of the first studies to validate SpA screening criteria in IBD patients in routine clinical practice.

Meta-Analysis and Validation of a Colorectal Cancer Risk Prediction Model Using Deep Sequenced Fecal Metagenomes.

The gut microbiome is a potential modifiable risk factor for colorectal cancer (CRC). We re-analyzed all eight previously published stool sequencing data and conducted an MWAS meta-analysis. We used cross-validated LASSO predictive models to identify a microbiome signature for predicting the risk of CRC and precancerous lesions. These models were validated in a new study, Colorectal Cancer Screening (COLSCREEN), including 156 participants that were recruited in a CRC screening context. The MWAS meta-analysis identified 95 bacterial species that were statistically significantly associated with CRC (FDR < 0.05). The LASSO CRC predictive model obtained an area under the receiver operating characteristic curve (aROC) of 0.81 (95%CI: 0.78−0.83) and the validation in the COLSCREEN dataset was 0.75 (95%CI: 0.66−0.84). This model selected a total of 32 species. The aROC of this CRC-trained model to predict precancerous lesions was 0.52 (95%CI: 0.41−0.63). We have identified a signature of 32 bacterial species that have a good predictive accuracy to identify CRC but not precancerous lesions, suggesting that the identified microbes that were enriched or depleted in CRC are merely a consequence of the tumor. Further studies should focus on CRC as well as precancerous lesions with the intent to implement a microbiome signature in CRC screening programs.

Proton-pump inhibitors are associated with a high false-positivity rate in faecal immunochemical testing.

BACKGROUND: False-positivity rates in faecal immunochemical test (FIT) can be affected by drug exposure. We aimed to assess the association between proton pump inhibitors (PPI) consumption and false positive (FP) results in a colorectal cancer (CRC) screening programme using electronic prescription records. METHODS: A retrospective cohort study within a population-based screening program for CRC from 2010 to 2016 was performed. Participants with a conclusive FIT result and with prescription electronic data were included. An FP result was defined as having a positive FIT (≥ 20 µg haemoglobin/g faeces) and a follow-up colonoscopy without intermediate or high-risk lesions or CRC. Screening data were anonymously linked to the public data analysis program for health research and innovation (PADRIS) database that recorded patient diseases history and reimbursed medication. PPI exposure was defined as having retrieved at least one dispensation of PPI three months prior to the FIT. RESULTS: A total of 89,199 tests (of 46,783 participants) were analysed, 4824 (5.4%) tested positive and the proportion of FP was 53.5%. Overall, 17,544 participants (19.7%) were PPI users prior to FIT performance. PPI exposure increased the probability of obtaining an FP FIT result from 50.4 to 63.3% (adjusted OR 1.39; 95% CI 1.18-1.65). Nonsteroidal anti-inflammatory drugs, acetylsalicylic acid, antibiotics, and laxatives were also associated with an FP result. The effect of PPI was independent and showed a synergistic interaction with nonsteroidal anti-inflammatory drugs. CONCLUSION: PPIs increase FIT positivity at the expense of FP results. The recommendation to avoid their use before FIT performance could reduce up to 3% of colonoscopies and 9% of FP results.