Involvement of IL17A and IL17RA variants in interleukin-17A levels and disease activity in ulcerative colitis.

Ulcerative colitis (UC) is characterized by chronic inflammation of the large intestine with involvement of Th17 cells and interleukin (IL)-17A. The role of IL17A and IL17A receptor (IL17RA) variants in pathophysiology of UC still remains inconclusive. The aim was to evaluate the association between IL17A and IL17RA variants with susceptibility, IL-17A plasma levels, and endoscopic activity in UC. The study included 104 patients with UC and 213 controls. Patients were divided according to endoscopic activity (remission/mild and moderate/severe). The IL17A rs3819024 A>G and rs3819025 G>A, and IL17RA rs2241043 C>T, rs2241049 A>G, and rs6518661 G>A variants were genotyped using real time polymerase chain reaction. IL-17A plasma levels were determined using immunofluorimetric assay. Neither IL17A nor IL17RA variants were associated with UC susceptibility. The IL17A rs3819024 AG genotype was associated to high levels of IL-17 only in patients. Patients with the G allele of IL17RA rs2241049 showed 2.944 more chance of developing moderate/severe disease. The haplotype analysis showed that IL17RA rs2241049 and rs6518661 was not associated with UC susceptibility and haplotypes constituted with G allele of these variants were not associated with disease severity (p = 0.09). In conclusion, the IL17A rs3819024 AG genotype was associated with elevated IL-17A plasma levels in patients with UC but not in controls and the IL17RA rs2241049 AG+GG genotypes were associated to severity of UC. These results suggest a possible hidden interaction between the IL17A rs3819024 variant and other genetic, environmental, and epigenetic factors in the IL-17A expression that is present only in patients with UC.

Combined use of CDAI and blood indices for assessing endoscopic activity in ileocolic Crohn's disease.

BACKGROUND: Mucosal healing has become the primary treatment target for patients with Crohn's disease (CD). We aimed to develop a noninvasive and convenient tool to evaluate the endoscopic activity in patients with ileocolic CD. METHODS: A retrospective multicenter study including 300 CD patients (training, 210 patients; test, 90 patients) was conducted at two tertiary referral centers. Independent risk factors associated with endoscopic activity were explored, which were then combined into a comprehensive index. The predictive performance was evaluated with the area under receiver operating characteristic curve (ROC). Cohen's Kappa was adopted to examine the consistency between each indicator and endoscopic activity. RESULTS: A total of 210 CD patients were recruited in the training cohort. We found that Crohn's Disease Activity Index (CDAI), C-reactive protein (CRP) and platelet-to-lymphocyte percentage ratio (PLpR) were independently associated with endoscopic activity. Additionally, the comprehensive index generated from the above three indices achieved good discrimination and performed better than CDAI in AUC (0.849 vs. 0.769, P < 0.05). This was further well demonstrated by the external test cohort, which showed good discrimination (AUC: 0.84, 95% CI: 0.744-0.936). Intra-individual comparison revealed the comprehensive index to be superior in the prediction of endoscopic activity. In the subgroup analysis, the AUC of comprehensive index was significantly higher than CDAI especially in inflammatory phenotype (0.824 vs. 0.751, P < 0.05). CONCLUSION: Combining CDAI, CRP and PLpR significantly improved the accuracy for predicting endoscopic activity in ileocolic CD, which can help better monitor an endoscopic flare.

Common laboratory blood test immune panel markers are useful for grading ulcerative colitis endoscopic severity.

BACKGROUND: At present, many indicators reflect the clinical disease activity of ulcerative colitis (UC). However, commonly used inflammatory markers do not show good utility for indicating endoscopic disease activity. The purpose of this study was to evaluate high sensitivity C-reactive protein (hs-CRP), C-reactive protein to albumin ratio (CAR), inflammatory markers, and complete blood count (CBC) related parameters in patients with UC as simple, non-invasive, and independent markers of endoscopic activity (EA). METHODS: We retrospectively collected extensive data from the hospital medical records of 386 patients who presented with UC to the First Affiliated Hospital of Xinjiang Medical University (Urumqi, China) from 2018 to 2022 January. The Mayo endoscopic score (MES) was used to evaluate endoscopic disease activity. All included patients were defined as the MES-All group; those with extensive colitis (E3) were defined as the MES-E3 group. Demographics, laboratory parameters, endoscopic results, the extent of disease, and drug history were recorded and analyzed. RESULTS: For patients in the MES-All or MES-E3 group, hs-CRP, CAR, neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR) were significantly higher in EA UC patients than in those with mucosal healing. The mean platelet volume (MPV) and lymphocyte to monocyte ratio were significantly lower in active disease than in the patient's remission (p < 0.001). ROC analysis showed that in the MES-All and MES-E3 groups, the cutoff values of hs-CRP activity under endoscopy were 5.32 mg/L (AUC 0.850, sensitivity 77.6%, specificity 81.9%) and 5.16 mg/L (AUC 0.902, sensitivity 86.9%, specificity 85.4%) respectively, and the cutoff values of CAR were 0.14 (AUC 0.853, sensitivity 76.8%, specificity 84.8%) and 0.18 (AUC 0.904, sensitivity 81.8%, specificity 89.6%) respectively. Multivariate logistic regression analysis showed that hs-CRP, CAR, NLR, and PLR identified UC EA, while decreased MPV reflected inflammatory activity in the UC mucosa. CONCLUSION: Especially in patients with extensive colitis, hs-CRP and CAR are closely related to EA and show a higher diagnostic value compared to the related CBC parameters. The aforementioned indicators are simple and non-invasive independent markers that reflect the EA in UC.

Endoscopic and histologic activity assessment considering disease extent and prediction of treatment failure in ulcerative colitis.

BACKGROUND AND AIMS: DUBLIN score allows evaluation of disease activity and extent in ulcerative colitis (UC). This study aimed to evaluate DUBLIN score as a predictor of therapeutic failure as well as to associate endoscopic and histological activity scores to assess their joint performance. METHODS: Retrospective cohort study, with consecutive inclusion of patients undergoing total colonoscopy with serial biopsies between 2016 and 2019. DUBLIN score (0-9) was calculated as the product of Mayo endoscopic score (MSe 0-3) by disease extent (E1-E3). Histological activity was evaluated through Nancy score (0-4). Activity scores were correlated with biomarkers, treatment failure (therapeutic escalation, hospitalization and/or colectomy) and clinical remission at 6 months (Mayo partial score ≤ 1). RESULTS: One-hundred and seven patients were included. In 38.3% (n = 41) there was evidence of endoscopic activity (MSe ≥ 2) and in 50.5% (n = 54) histological activity (Nancy ≥ 2). MSe and DUBLIN scores showed good correlation (r = 0.943; p < .001) and both were significantly higher in patients with histological activity (p < .001). Therapeutic failure occurred in 25.2% (n = 27). MSe, DUBLIN, and Nancy scores were significantly associated with therapeutic failure (p < .001). The areas under the (AUC) ROC curve were 0.74 (MSe; p < .001), 0.78 (DUBLIN; p < .001) and 0.84 (Nancy; p < .001). Joint evaluation of endoscopic and histological activity by combining DUBLIN and Nancy scores was associated with therapeutic failure with a significantly higher AUC of 0.84 (p < .001) compared to the Dublin score alone (p = .003). CONCLUSION: Mayo and DUBLIN endoscopic scores correlated with each other and with histological activity. The joint evaluation of endoscopic and histological activity allowed to predict with greater accuracy treatment failure.

Role of faecal calprotectin as a predictor of endoscopic activity in paediatric patients with ulcerative colitis.

INTRODUCTION: Colonoscopy is currently considered to be the gold standard for evaluation of colonic mucosa inflammation in patients with ulcerative colitis (UC), but the procedure is invasive and cannot be repeated frequently, especially in the paediatric population. The aim of this study was to assess the role of faecal calprotectin (FC) as a predictor of endoscopic disease activity in paediatric patients with UC in clinical remission. MATERIAL AND METHODS: Single-centre prospective study. Clinical remission was defined as Paediatric Ulcerative Colitis Activity Index <10. Endoscopic findings were assessed according to the Mayo Endoscopic Subscore (MES). MES≤1 was defined as endoscopic remission. All participants provided fresh faecal samples for measurement of FC. RESULTS: A total of 34 visits of 24 children with UC were included in the study. There was a strong positive correlation between FC levels and endoscopic disease activity (n=34, r=0.83, p<0.001). The median FC levels in the subgroup with endoscopic activity (MES 2-3) were significantly higher than the median FC levels in the subgroup without endoscopic activity (MES≤1) (1000µg/g, IQR 575-1800µg/g vs. 100µg/g, IQR 80-223µg/g, p<0.001). At a cut-off of 298.5µg/g, FC had 92.3% sensitivity, 95.2% specificity and an AUROC 0.974 (SE 0.023, 95% CI 0.93-1, p<0.001) to predict endoscopic activity. DISCUSSION: FC is an accurate surrogate marker of endoscopic activity in children with clinically quiescent UC.

Faecal calprotectin level for assessing endoscopic activity and predicting future clinical course in patients with moderately active ulcerative colitis undergoing granulomonocytapheresis: a prospective cohort study.

BACKGROUND: Calprotectin is a stable neutrophil protein, which can be measured in faecal samples. The faecal level of calprotectin increases during disease activity in ulcerative colitis (UC). Nonetheless, the relevance of faecal calprotectin (FC) measurement during granulomonocytapheresis (GMA) for UC has not yet been fully evaluated. This prospective study was to investigate the value of FC for assessing disease activity and predicting clinical course in UC patients undergoing GMA therapy. METHODS: One hundred and eighty-four patients with moderately active UC with endoscopic activity (Mayo endoscopic subscore [MES] = 2 or 3) received Adacolumn GMA therapy (10 apheresis sessions over consecutive 5 weeks). Patients who achieved clinical remission were subsequently given maintenance medications for 12 months. FC levels were measured at entry and after treatment. RESULTS: After GMA, 80 of the 184 patients (43%) achieved clinical remission, and 51 (28%) achieved mucosal healing (MH; MES = 0 or 1). The median FC level significantly decreased in patients who achieved MH (P = 0.02), but not in those without MH. Thirty-four patients (43%) relapsed during the 12-month follow-up. The median FC level at the end of GMA therapy was significantly higher in patients who subsequently relapsed than in those who maintained remission (149.5 vs 45.5 µg/g, P < 0.001). A cut off value of 114 µg/g had a sensitivity of 76% and a specificity of 85% to predict future relapse. CONCLUSIONS: Our findings indicate that FC is a relevant biomarker, which is convenient to measure for assessing endoscopic activity and predicting relapse in patients who achieve remission following a course of GMA therapy.

Correlation between serological biomarkers and endoscopic activity in patients with inflammatory bowel disease.

BACKGROUND/AIMS: Endoscopy is the gold standard for assessing disease severity in inflammatory bowel disease (IBD), although it is an invasive procedure. Biological markers have been routinely used as a non-invasive means of determining disease activity. The aim of this study was to determine the correlation between common biological markers and endoscopic activity in IBD. METHODS: Consecutive patients with IBD were included. Serum concentrations of different biomarkers (C-reactive protein [CRP], orosomucoid [ORM], erythrocyte sedimentation rate [ESR], fibrinogen, platelets, leukocytes, neutrophils and hemoglobin [Hb]) were measured, and their accuracy in detecting endoscopic activity was determined. RESULTS: Eighty patients were included (mean age 46 years, 53% Crohn's disease), 70% with endoscopic activity. Among Crohn's disease patients, 24% had mild endoscopic activity, 12% moderate activity and 39% severe activity. Among ulcerative colitis patients, 35% had an endoscopic Mayo score of 0-1 points, 30% 2 points and 35% 3 points. None of the biomarkers included had a good correlation with endoscopic activity (Area Under the ROC curve [AUC]<0.70) in ulcerative colitis. ORM, fibrinogen and platelets had the best accuracy to detect endoscopic activity in Crohn's disease (AUC: 0.80-0.085). A sub-analysis in postoperative Crohn's disease patients found no correlation between endoscopic recurrence and biomarkers (AUC<0.70). CONCLUSION: Serological biomarkers, including CRP, have low accuracy to detect endoscopic activity in ulcerative colitis and postoperative Crohn's disease. ORM, fibrinogen and platelets have the best accuracy to detect endoscopic activity in Crohn's disease.

The recovery of endoscopic activity and cancer detection after the COVID-19 pandemic.

Background: The COVID-19 pandemic had a substantial impact on cancer services. The aim of our study was to evaluate the recovery of endoscopic activity and cancer detection after the COVID-19 pandemic. Methods: Endoscopic data from January 2019 to December 2020 were retrospectively collected to assess the endoscopic activity and cancer detection during the COVID-19 peak period (February 2020) and the post-COVID-19 peak period (March to July 2020). Results: The COVID-19 pandemic almost brought endoscopic activity and cancer detection to a standstill. Diagnostic procedure and endoscopic resection showed the greatest reduction. With the decline in COVID-19 infections, endoscopic activity gradually returned to previous level in July. However, the detection rate of gastric cancer resumed in September, whereas colorectal cancer resumed in August. The monthly detection rates of gastric and colorectal cancers decreased from their initial peaks of 2.98 % and 6.45 %, respectively, and finally were even lower than the average in 2019. Similarly, the mean age of patients who received endoscopy also declined as the detection rates resumed. The increasing colonoscopies allowed the missing colorectal cancer patients to be caught up. In contrast, it was expected that 6.69 % of gastric cancer patients were missed and did not receive needed endoscopy. Conclusions: The recovery of cancer detection occurred later than that of endoscopic activity, especially for gastric cancer. Older people were vulnerable to the continuous impact of COVID-19 pandemic than young people for seeking medical services. Urgent efforts are required to recover and maintain cancer services before subsequent waves of the COVID-19 pandemic.

Development and validation of multiparametric models based on computed tomography enterography to determine endoscopic activity and surgical risk in patients with Crohn's disease: A multi-center study.

Objective: To develop novel multiparametric models based on computed tomography enterography (CTE) scores to identify endoscopic activity and surgical risk in patients with Crohn's disease (CD). Methods: We analyzed 171 patients from 3 hospitals. Correlations between CTE outcomes and endoscopic scores were assessed using Spearman's rank correlation analysis. Predictive models for moderate to severe CD were developed, and receiver operating characteristic (ROC) curves were constructed to determine the area under the ROC curve (AUC). A combined nomogram based on CTE scores and clinical variables was also developed for predicting moderate to severe CD and surgery. Results: CTE scores were significantly correlated with endoscopy scores at the segment level. The global CTE score was an independent predictor of severe (HR = 1.231, 95% CI: 1.048-1.446, p = 0.012) and moderate-to-severe Simplified Endoscopic Scores for Crohn's Disease (SES-CD) (HR = 1.202, 95% CI: 1.090-1.325, p < 0.001). The nomogram integrating CTE and clinical data predicted moderate to severe SES-CD and severe SES-CD scores in the validation cohort with AUCs of 0.837 and 0.807, respectively. The CTE score (HR = 1.18; 95% CI: 1.103-1.262; p = 0.001) and SES-CD score (HR = 3.125, 95% CI: 1.542-6.33; p = 0.001) were independent prognostic factors for surgery-free survival. A prognostic nomogram incorporating CTE scores, SES-CD and C-reactive protein (CRP) accurately predicted the risk of surgery in patients with CD. Conclusion: The newly developed CTE score and multiparametric models displayed high accuracy in predicting moderate to severe CD and surgical risk for CD patients.

Impact of Baseline Disease Activity and Trial Duration on Efficacy of Biologics in Active Crohn's Disease: Meta-analysis.

BACKGROUND: Timings of assessment of efficacy and criteria used to define Crohn's disease (CD) activity at baseline may affect therapeutic gain of active drug over placebo in induction of remission trials in CD, but these issues have not been assessed systematically. We examined these issues in a meta-analysis. METHODS: We searched the literature to June 2022 for randomized controlled trials of biologics vs placebo in active CD. We extracted clinical remission and response rates according to criteria used to define CD activity and time point of assessment, pooling them in a meta-analysis for all patients according to previous biologic exposure. We calculated the number needed to treat (NNT), with a 95% confidence interval (CI) to assess therapeutic gain of active drug over placebo according to these characteristics of trial design. RESULTS: We identified 20 induction of remission trials (6754 patients). Rates of clinical remission were highest (42.6% with active drug vs 21.0% with placebo) and NNT lowest (5; 95% CI, 3-7.5) in trials using clinical and endoscopic activity to define active CD. Rates of remission were lower (26.5% with active drug, vs 18.6% with placebo) and NNT highest (12; 95% CI, 6-61) in trials using clinical activity alone. Results were similar according to previous biologic exposure. Time point of assessment seemed to have less of an effect, although the NNT was lowest in trials assessing remission rates at 9 to 12 weeks (NNT = 5.5; 95% CI, 4-8). Again, results were similar according to previous biologic exposure. CONCLUSIONS: Both the criteria used to define CD activity at study entry and the time point used to confirm efficacy may be important in maximizing therapeutic gain of active drug over placebo.

In this systematic review and meta-analysis of randomized controlled trials of biologics vs placebo in active CD, both the criteria used to define CD activity at study entry and the time point used to confirm efficacy appeared to be important in maximizing therapeutic gain of active drug over placebo.

Evaluation of intestinal ultrasound for disease activity assessment in patients with inflammatory bowel disease: A cross-sectional study at a tertiary centre in Malaysia.

Background: The use of intestinal ultrasound (IUS) in the management of inflammatory bowel disease (IBD) is emerging. We aim to determine the performance of IUS in the assessment of disease activity in IBD. Methods: This is a prospective cross-sectional study of IUS performed on IBD patients in a tertiary centre. IUS parameters including intestinal wall thickness, loss of wall stratification, mesenteric fibrofatty proliferation, and increased vascularity were compared with endoscopic and clinical activity indices. Results: Among the 51 patients, 58.8% were male, with a mean age of 41 years. Fifty-seven percent had underlying ulcerative colitis with mean disease duration of 8.4 years. Against ileocolonoscopy, IUS had a sensitivity of 67% (95% confidence interval (CI): 41-86) for detecting endoscopically active disease. It had high specificity of 97% (95% CI: 82-99) with positive and negative predictive values of 92% and 84%, respectively. Against clinical activity index, IUS had a sensitivity of 70% (95% CI: 35-92) and specificity of 85% (95% CI: 70-94) for detecting moderate to severe disease. Among individual IUS parameters, presence of bowel wall thickening (>3 mm) had the highest sensitivity (72%) for detecting endoscopically active disease. For per-bowel segment analysis, IUS (bowel wall thickening) was able to achieve 100% sensitivity and 95% specificity when examining the transverse colon. Conclusions: IUS has moderate sensitivity with excellent specificity in detecting active disease in IBD. IUS is most sensitive in detecting a disease at transverse colon. IUS can be employed as an adjunct in the assessment of IBD.

Effectiveness of swapping to ustekinumab after vedolizumab failure in patients with multi-refractory Crohn's disease.

BACKGROUND: Ustekinumab (UST) and vedolizumab (VDZ) are biologic therapies for moderate-to-severe Crohn's disease (CD) in patients who failed or had contraindication to anti-TNF treatment. AIMS: To evaluate ustekinumab efficacy as third-line treatment after swapping from VDZ for failure. METHODS: We conducted a monocentric, retrospective, observational study where CD patients were followed for 12 months from the beginning of UST therapy. We assessed clinical activity (HBI) and laboratory markers (CRP) at the initiation of UST therapy (T0) and after 2(T2), 6(T6) and 12(T12) months. Endoscopic activity was recorded at T0 and T12. We registered data regarding their clinical history and previous biologic treatments. Steroid-free clinical remission was defined as HBI ≤ 4 without need for steroids. Clinical response was defined as HBI reduction of at least three points or the suspension of steroids. RESULTS: 27 CD patients treated with UST after VDZ failure had a minimum follow up of 12 months and were included. All patients had previously been treated with anti-TNF agents. After 12 months, steroid-free clinical remission was evident in 15 (55.5%) patients, 5 (18.5%) had clinical response, while 7 (26%) had suspended for failure or persisted on treatment after optimization. CONCLUSIONS: Ustekinumab should be considered as third-line biologic treatment in multi-refractory CD patients.

An Improved Score for the Evaluation of Mucosal Healing in Inflammatory Bowel Disease-A Pilot Study.

Inflammatory bowel diseases are chronic conditions characterized by periods of remission, alternating with episodes of exacerbation, in which the primary therapeutic target is mucosal healing. Although colonoscopy is currently considered the gold standard for assessing disease activity, it presents a significant number of disadvantages. Over time, various inflammatory biomarkers have been proposed to detect disease activation, but current biomarkers have many limitations. Our study aimed to analyze the most commonly used biomarkers for patient monitoring and follow-up both independently and taken together as a group, in order to propose an improved activity score that more accurately reflects the changes occurring at the intestinal level, in order to limit the number of colonoscopic interventions. By applying logistic regression as a method of statistical analysis to the retrospectively collected data, we obtained an easy-to-calculate improved score that quantifies the chance that a given patient may be in remission or in a period of endoscopic activity. To achieve a widely accessible score that is easily accessible in clinical practice, we have included only the most commonly used clinical and biological parameters.

Risk prediction model based on blood biomarkers for predicting moderate to severe endoscopic activity in patients with ulcerative colitis.

Object: We explored developing an internal validation model to predict the moderate to severe endoscopic activity of ulcerative colitis (UC) patients based on non-invasive or minimally-invasive parameters. Methods: Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and Mayo endoscopic subscore were performed for UC patients who met the criteria from January 2017 to August 2021 through the electronic database of our center. Logistic regression and a least absolute shrinkage and selection operator (Lasso) regression model were performed to screen the risk factors of moderate to severe UC activity. The nomogram was established subsequently. Discrimination of the model was evaluated using the concordance index (c-index), and the calibration plot and 1,000 Bootstrap were used to evaluate the model's performance and conduct internal validation. Results: Sixty-five UC patients were included in this study. According to UCEIS criteria,45 patients were moderate to severe endoscopic activity. 26 potential predictors of UC were analyzed by logistic and Lasso regression showed that vitamin D (Vit D), albumin (ALB), prealbumin (PAB), and fibrinogen (Fbg) were the best predictors of moderate to severe endoscopic activity of UC. We used these 4 variables to develop a dynamic nomogram prediction model. The c-index was 0.860, which means good discrimination. The calibration plot and Bootstrap analysis showed that the prediction model accurately distinguished the moderate to severe endoscopic activity in UC patients. The prediction model was verified using a cohort of UC patients with moderate to severe activity defined by the Mayo endoscopic subscore, and it was found that the model still had good discrimination and calibration (c-index = 0.891). Conclusion: The model containing Vit D, ALB, PAB, and Fbg was a good tool for evaluating UC activity. The model is simple, accessible, and user-friendly, which has broad application prospects in clinical practice.

Serum Activin A Is a Novel Biomarker of Endoscopic Activity in Ulcerative Colitis.

Background: Endoscopic healing (EH) is the long-term therapeutic goal for ulcerative colitis (UC). Since repeated colonoscopies are inconvenient and invasive, a surrogate biomarker for endoscopic activity is needed. Activin A is one of the transforming growth factor-ß superfamily of proteins and has been shown to be associated with intestinal inflammation. Methods: This single-center observational study included 27 Japanese patients with UC in clinical remission who underwent colonoscopy and blood sampling. We investigated the correlations between laboratory parameters, including serum activin A levels, and endoscopic activity, classified by the Mayo endoscopic subscore (MES) in these patients. Results: This study included 15 males and 12 females. The median age was 44.0 years. In terms of endoscopic activity, five patients were diagnosed with MES 0, 14 patients with MES 1, seven patients with MES 2, and one patient with MES 3. The median serum activin level was 134.8 pg/mL (interquartile range (IQR), 105.3 - 188.1). Serum activin A levels were significantly correlated with the MES (Spearman's rank correlation coefficient r = 0.591, P = 0.001), which was better than that of C-reactive protein (CRP) (r = 0.487, P = 0.010). In the comparison between the EH group (MES 0) and non-EH group (MES 1-3), patients without EH had significantly higher serum activin A levels (Mann-Whitney U test, P = 0.047). A cutoff value of 133.6 pg/mL indicated non-EH with a sensitivity and specificity of 0.682 and 1.000, respectively. The area under the curve (AUC) of serum activin A for detecting non-EH was 0.791 (95% confidence interval (CI), 0.618 - 0.964), while that of CRP was 0.723 (95% CI, 0.504 - 0.941). Conclusions: The serum activin A level is a potential novel biomarker of endoscopic activity in UC.

Serum Elabela level is related to endoscopic activity index in patients with active ulcerative colitis.

BACKGROUND: In ulcerative colitis patients, Elabela levels and the relation of Elabela with laboratory parameters is unknown. AIM: The purpose of this study was to investigate the serum Elabela levels in UC patients and its relationship with other clinical and laboratory findings. METHODS: Forty-three patients with UC and 40 healthy controls (group I) similar in age and gender were included in the study. Routine patient history, physical examination, and laboratory tests were followed by analysis of serum Elabela levels. Endoscopic activity index (EAI) of patients with UC was calculated. There were two groups of patients: those in remission (group II) and with active disease (group III). RESULTS: Groups I, II, and III had 40, 22, and 21 participants, respectively. Serum Elabela levels were found to be 3.32 ± 1.25 ng/mL in group I, 3.38 ± 0.88 ng/mL in group II, and 5.48 ± 1.61 ng/mL in group III. Comparing the serum Elabela levels, a statistically significant difference was found between three groups (p < 0.001). Serum Elabela level showed a significant and positive correlation with EAI, leukocyte count, and hs-CRP, while a negative correlation was found with hemoglobin levels in univariate analysis (p < 0.001, for each). In linear regression analysis, these parameters were found to be associated with EAI and hs-CRP (p = 0.049, ß = 0.337, and p = 0.015, ß = 0.396, respectively). CONCLUSION: Elabela concentrations in patients with active UC was significantly higher and was associated with EAI and hs-CRP. Blood Elabela concentrations can be useful in the diagnosis and follow-up of patients with active UC.

Endoscopy during the peak of COVID-19 pandemic: impact on activity and financial implications for a tertiary referral center in London.

BACKGROUND: COVID-19 pandemic is an unprecedented global medical emergency. National and international gastrointestinal societies recommended that any endoscopic activity during the lockdown phase of the pandemic should be limited to emergency or non-deferrable procedures only. We assessed the financial implications and impact on endoscopy activity of the lockdown phase in a tertiary referral endoscopy unit. METHODS: The number of endoscopy procedures canceled and performed in our endoscopy unit during our "delay phase" (16-22/03/2020) and "lockdown phase" (23/03-29/05/2020) was reviewed and compared with endoscopy activity conducted during the same period in 2019. The financial impact was subsequently analyzed. RESULTS: Between 16/03/2020 and 29/05/2020, 683 procedures were canceled and 365 non-deferrable procedures were performed. In contrast, in 2019, 3437 procedures were performed over the same timeframe, resulting in a revenue contraction of approximately €2,062,857. We estimated that the number of lists required to recuperate the canceled endoscopic activity, ranges from 103-155, depending on the level of personal protective equipment required and mitigating policy relating to COVID-19. CONCLUSION: Our results highlight that COVID-19 pandemic had a substantial negative impact on our endoscopy activity and on the revenue generated by our endoscopy unit.

Urotensin II levels in patients with inflammatory bowel disease.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are associated with increased cardiovascular risk and have increased overall cardiovascular burden. On the other hand, urotensin II (UII) is one of the most potent vascular constrictors with immunomodulatory effect that is connected with a number of different cardiometabolic disorders as well. Furthermore, patients with ulcerative colitis have shown increased expression of urotensin II receptor in comparison to healthy controls. Since the features of IBD includes chronic inflammation and endothelial dysfunction as well, it is plausible to assume that there is connection between increased cardiac risk in IBD and UII. AIM: To determine serum UII levels in patients with IBD and to compare them to control subjects, as well as investigate possible associations with relevant clinical and biochemical parameters. METHODS: This cross sectional study consecutively enrolled 50 adult IBD patients (26 with Crohn's disease and 24 with ulcerative colitis) and 50 age and gender matched controls. Clinical assessment was performed by the same experienced gastroenterologist according to the latest guidelines. Ulcerative Colitis Endoscopic Index of Severity and Simple Endoscopic Score for Crohn's Disease were used for endoscopic evaluation. Serum levels of UII were determined using the enzyme immunoassay kit for human UII, according to the manufacturer's instructions. RESULTS: IBD patients have significantly higher concentrations of UII when compared to control subjects (7.57 ± 1.41 vs 1.98 ± 0.69 ng/mL, P < 0.001), while there were no significant differences between Crohn's disease and ulcerative colitis patients (7.49 ± 1.42 vs 7.65 ± 1.41 ng/mL, P = 0.689). There was a significant positive correlation between serum UII levels and high sensitivity C reactive peptide levels (r = 0.491, P < 0.001) and a significant negative correlation between serum UII levels and total proteins (r = -0.306, P = 0.032). Additionally, there was a significant positive correlation between serum UII levels with both systolic (r = 0.387, P = 0.005) and diastolic (r = 0.352, P = 0.012) blood pressure. Moreover, serum UII levels had a significant positive correlation with Ulcerative Colitis Endoscopic Index of Severity (r = 0.425, P = 0.048) and Simple Endoscopic Score for Crohn's Disease (r = 0.466, P = 0.028) scores. Multiple linear regression analysis showed that serum UII levels retained significant association with high sensitivity C reactive peptide (ß ± standard error, 0.262 ± 0.076, P < 0.001) and systolic blood pressure (0.040 ± 0.017, P = 0.030). CONCLUSION: It is possible that UII is involved in the complex pathophysiology of cardiovascular complications in IBD patients, and its purpose should be investigated in further studies.

Comparing the Continuous Geboes Score With the Robarts Histopathology Index: Definitions of Histological Remission and Response and their Relation to Faecal Calprotectin Levels.

BACKGROUND AND AIMS: The histological status of ulcerative colitis [UC] patients in clinical and endoscopic remission has gained space as an important prognostic marker and a key component of disease monitoring. Our main aims were to compare two histological indexes-the continuous Geboes score [GS] and the Robarts Histopathology index [RHI]-regarding their definitions of histological remission and response, and the ability of faecal calprotectin [FC] levels to discriminate between these statuses. METHODS: This was an analysis of three prospective cohorts including 422 patients previously enrolled in other studies. RESULTS: The two continuous scores [GS and RHI] were shown to be significantly correlated [correlation coefficient of 0.806, p < 0.001] and particularly close regarding their definition of histological response: 95% and 88% of all patients classified as having/not having [respectively] histological response according to RHI also did so according to GS. Moreover, median FC levels in patients with histological response were lower than those in patients without histological response [GS: 73.00 vs 525.00, p < 0.001; RHI: 73.50 vs 510.00, p < 0.001]; a similar trend was observed when FC levels of patients in histological remission were compared to those of patients with histological activity [GS: 76.00 vs 228.00, p < 0.001; RHI: 73.50 vs 467.00, p < 0.001]. FC levels allowed us to exclude the absence of histological remission [according to RHI] and absence of histological response [according to RHI and GS], with negative predictive values varying from 82% to 96%. However, optimization of the FC cut-off to exclude the absence of histological remission, as for the continuous GS, falls within values that resemble those of the healthy population. CONCLUSION: The continuous GS and RHI histological scores are strongly correlated in their definitions of histological response. An absence of histological remission could only be excluded at physiological levels of FC.

Endoscopic activity, tissue factor and Crohn's disease: findings in clinical remission patients.

BACKGROUND: As Crohn's disease (CD) is associated with a high risk of thromboembolic events (TE), including patients with subclinical inflammation, we aim to evaluate the correlation between the impact of endoscopic activity (EA) in the coagulation profiling of CD patients while in clinical remission. METHODS: From 164 consecutive CD patients included in clinical remission [Crohn's disease activity index (CDAI) < 150], 75 were in the EA group [Simplified Endoscopic Score for CD (SES-CD) ⩾ 7], 89 were in the endoscopic remission (ER) group (SES-CD ⩽ 2), and 50 were included as healthy controls in the study. Blood samples were analyzed for tissue factor (TF), factor VIII (FVIII), thrombomodulin (TM), ADAMTS-13, von Willebrand factor (VWF), and endogenous thrombin potential (ETP), as well as collecting data regarding risk factors for TE and CD profile. RESULTS: Mean plasma TF activity showed significantly higher levels in the EA group when compared with the ER and control groups (127 pM versus 103 pM versus 84 pM; p = 0.001), although the VWF:Ag (160% versus 168% versus 110%; p = 0.001), VWF/ADAMTS-13 (191 versus 219 versus 138; p = 0.003), FVIII (150% versus 144% versus 90%; p = 0.001) and TM (5.13 ng/ml versus 4.91 ng/mL versus 3.81 ng/ml; p < 0.001) were only increased in CD regardless of EA status when compared with controls. Lastly, ETP with and without TM remained the same in all three groups. CONCLUSIONS: CD patients in clinical remission with EA present endothelial lesion inducing TF exposure and subsequent coagulation cascade activation. Recommended thromboprophylaxis for EA outpatient subgroups will require additional investigation in order to be validated.