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

2019 ◽  
Vol 14 (2) ◽  
pp. 169-175 ◽  
Author(s):  
Fernando Magro ◽  
Joanne Lopes ◽  
Paula Borralho ◽  
Susana Lopes ◽  
Rosa Coelho ◽  
...  
Keyword(s):  
Healthy Population ◽  
Strongly Correlated ◽  
Histological Response ◽  
Faecal Calprotectin ◽  
Predictive Values ◽  
Endoscopic Remission ◽  
Prospective Cohorts ◽  
Histological Activity ◽  
Histological Remission ◽  
Definition Of

Abstract 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.

Comparison of the Nancy Index With Continuous Geboes Score: Histological Remission and Response in Ulcerative Colitis

2020 ◽  
Vol 14 (7) ◽  
pp. 1021-1025 ◽  
Author(s):  
Fernando Magro ◽  
Joanne Lopes ◽  
Paula Borralho ◽  
Cláudia Camila Dias ◽  
Joana Afonso ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Correlation Coefficient ◽  
Area Under The Curve ◽  
Clinical Relapse ◽  
Strongly Correlated ◽  
Histological Response ◽  
Faecal Calprotectin ◽  
Histological Activity ◽  
Histological Remission

Abstract Background and Aims Evidence has been supporting that histological activity of ulcerative colitis [UC] has relevance for the prediction of clinical outcomes in UC patients, such as clinical relapse. In this study, we aimed to compare two histological indexes—the continuous Geboes score [GS] and the Nancy index [NI] —regarding their definitions of histological remission and response, and to determine the ability of faecal calprotectin [FC] levels to discriminate between these histological statuses according to the NI. Methods A large cohort of UC patients [N = 422] who were previously enrolled in other studies was analysed. Results GS and NI were shown to be strongly correlated [correlation coefficient: 0.882, p <0.001], indicating high accordance in the classification of patients as having/not having histological remission and response. FC levels moderately correlated with NI regarding these histological statuses [correlation coefficient: 0.481, p <0.001], moderately predicted the absence of remission defined by NI >0 {area under the curve (AUC) 0.667 (95% confidence interval [CI] 0.609–0.724)}, and were good predictors of the absence of histological response defined by NI >1 (AUC 0.825 [95% CI 0.777–0.872]). The optimal FC cut-offs determined to predict the NI-defined histological remission and response were 91 μg/g and 106 μg/g, when maximising the negative predictive value [NPV]. Conclusions Due to the higher applicability of the NI, this study encourages the systematic use of this histological index to assess histological remission and response in UC patients.

scholarly journals Can fecal calprotectin accurately identify histological activity of ulcerative colitis? A meta-analysis

2021 ◽  
Vol 14 ◽  
pp. 175628482199474
Author(s):  
Xiaoqi Ye ◽  
Ying Wang ◽  
Harry H. X. Wang ◽  
Rui Feng ◽  
Ziyin Ye ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Meta Analysis ◽  
Area Under The Curve ◽  
Fecal Calprotectin ◽  
Secondary Outcome ◽  
Histological Response ◽  
Summary Receiver Operating Characteristic ◽  
Histological Activity ◽  
Histological Remission ◽  
Sensitivity Specificity

Background and Aims: Elevated fecal calprotectin (FC) levels have been reported to correlate with histological activity in patients with ulcerative colitis (UC). However, the accuracy of FC for evaluating histological activity of UC remains to be determined. The aim of this study was to determine the accuracy of FC for evaluating histological activity of UC, based on updated definitions. Methods: Related studies were retrieved from the PubMed, Web of Science, Embase, and Cochrane databases. Adult participants diagnosed with UC were included when sufficient data could be extracted to calculate the accuracy of FC for evaluating histological activity. The primary outcome was histological response, and the secondary outcome was histological remission, defined according to a recently updated position paper of European Crohn’s and Colitis Organization. Statistics were pooled using bivariate mixed-effects models. The area under the curve was estimated by summary receiver-operating characteristic curves. Results: Nine studies were included, from which 1039 patients were included for the analysis of histological response and 591 patients for histological remission. For the evaluation of histological response, the pooled sensitivity, specificity, and the area under the curve were 0.69 [95% confidence interval (CI): 0.52–0.82], 0.77 (95% CI: 0.63–0.87), and 0.80 (95% CI: 0.76–0.83), respectively. For the evaluation of histological remission, the corresponding estimates were 0.76 (95% CI: 0.71–0.81), 0.71 (95% CI: 0.62–0.78), and 0.79 (95% CI: 0.75–0.82), respectively. FC had a higher accuracy in studies using Nancy Index. For histological response, the cut-off values of FC ranged from 50 to 172 µg/g, and the sensitivity was higher in studies with FC cut-off values >100 µg/g (0.77 versus 0.65). Conclusion: FC is a valuable biomarker for assessing histological activity in patients with UC. A cut-off value of 100–200 µg/g is more appropriate to spare patients from an unnecessary endoscopy and biopsy.

scholarly journals P545 Calprotectin at week 12 is a predictor for histological remission in ulcerative colitis patients treated with Vedolizumab

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S515-S516
Author(s):  
D Rubstov ◽  
P Kakkadasam Ramaswamy ◽  
J Edwards ◽  
D Shukla ◽  
L Willmann ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Remission ◽  
Real World Setting ◽  
Endoscopic Remission ◽  
Endoscopic Score ◽  
Histological Activity ◽  
Maintenance Of Remission ◽  
Histological Remission ◽  
Endoscopic Assessment

Abstract Background Vedolizumab (VDZ) is a gut-specific α4β7 integrin antagonist that has demonstrated efficacy for induction and maintenance of remission in moderate to severe ulcerative colitis (UC). The aim of this study was to assess the rates of histological remission (HR) in a real-world setting and to identify predictors for histological remission. Methods Retrospective cohort study of all UC patients (≥18 years) initiated on VDZ from 2016 to 2020 was completed. Clinical, biochemical, endoscopic and histologic data were collected. All patients received standard induction therapy with VDZ 300 mg IV at Weeks 0, 2, and 6 and maintained on an 8-weekly regimen. Dose was escalated to a every 4-weekly regimen as per physician’s discretion. A 52-week follow-up was completed on all patients. Endoscopic assessment was carried out between 24 and 52 weeks after commencing VDZ. Histological activity was graded as per Nancy index and histological remission was defined as Nancy grade 0. Endoscopic remission was defined as Mayo endoscopic score = 0. Clinical remission was defined as SCCAI ≤ 5. Results A total of 51 patients [55% female, median age 48 years (IQR 35–60)] were included. 16/51 (34%) were anti-TNF exposed. In 30/51 (59%) patients VDZ was combined with steroids at induction and by week 12 steroids were completely tapered in 14/30 (46.7%) patients. At weeks 12, 24 and 52, 89.6%, 87% and 97.5% of patients, respectively, were in clinical remission. 19/37 (51.3%) patients were in endoscopic remission at end of follow up. Median Nancy score prior to commencing VDZ was 3 (IQR: 2–4) and the median Nancy score at end of follow up was 1 (IQR: 0–2). 19/37 (51.3%) patients achieved HR; 3 patients who were in HR at the time of commencement of VDZ remained in HR at the end of follow up. Median baseline faeces calprotectin (FC) was 320 mcg/g (IQR 45–1000) and was similar in patients who achieved HR and those who did not. Median FC at 12 weeks was 155 mcg/g (45–720) and was significantly lower in patients who achieved HR when compared to patients who did not achieve histological remission (45 vs 420, p 0.028). FC at week 12 predicted histological remission (AUC =0.8667). FC ≥ 200mcg/g at week 12 predicted failure to achieve HR with sensitivity 70%, specificity 100%, PPV 100%, NPV 75%, accuracy 84%. Conclusion Vedolizumab is effective in achieving histological remission and FC ≥ 200 mcg/g at week 12 accurately predicts failure to achieve HR in patients treated with VDZ.

scholarly journals Low Golimumab Trough Levels at Week 6 Are Associated With Poor Clinical, Endoscopic and Histological Outcomes in Ulcerative Colitis Patients: Pharmacokinetic and Pharmacodynamic Sub-analysis of the Evolution Study

2019 ◽  
Vol 13 (11) ◽  
pp. 1387-1393 ◽  
Author(s):  
F Magro ◽  
S Lopes ◽  
M Silva ◽  
R Coelho ◽  
F Portela ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Objective Response ◽  
Early Response ◽  
Induction Phase ◽  
Open Label ◽  
Faecal Calprotectin ◽  
Mayo Score ◽  
Histological Activity ◽  
Histological Remission ◽  
Trough Levels

Abstract Background and Aims Golimumab has an established exposure-response relationship in patients with ulcerative colitis [UC]. However, the association of serum golimumab trough levels [TL] with objective markers of disease activity, such as endoscopic and histological activity scores and concentrations of biomarkers, remains less understood. This report describes the relationship of serum golimumab TL at the end of the induction period [Week 6] with clinical, endoscopic, histological, and biomarker parameters. Methods This was an open-label, uncontrolled, prospective and interventional study. Moderate to severely active UC patients naïve to biologic therapy were treated with golimumab. Serum golimumab TL and faecal calprotectin levels were measured at baseline [Week 0 of induction] and Week 6. Results A total of 34 patients completed the induction phase [Week 6] and were included in this analysis. Overall, 47.1% and 14.7% of patients achieved clinical response and remission with significantly higher serum golimumab TL in patients with early response or remission [3.7 μg/mL vs 1.3 μg/mL, p = 0.0013; and 3.1 μg/mL vs 1.7 μg/mL, p = 0.0164, respectively]. In addition, golimumab TL were significantly higher in patients achieving histological remission [4.2 μg/mL vs 1.7 μg/mL, p = 0.0049]. Week 6 golimumab TL were inversely correlated with the total Mayo score [rs = -0.546; p = 0.0008], the Mayo endoscopic subscore [rs = -0.381; p = 0.0262], the Geboes histological activity score [rs = -0.464; p = 0.0057], and faecal calprotectin levels [rs = -0.497; p = 0.0044]. Conclusions A higher early exposure to golimumab is associated with a better objective response in active UC patients and appears to drive the outcome at Week 6.

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

Gut ◽  
2018 ◽  
Vol 68 (4) ◽  
pp. 594-603 ◽  
Author(s):  
Fernando Magro ◽  
Joanne Lopes ◽  
Paula Borralho ◽  
Susana Lopes ◽  
Rosa Coelho ◽  
...  
Keyword(s):  
Sensitivity And Specificity ◽  
Intestinal Mucosa ◽  
Scoring Systems ◽  
Classification Systems ◽  
Histological Classification ◽  
Faecal Calprotectin ◽  
Endoscopic Score ◽  
Histological Activity ◽  
Good Concordance ◽  
Histological Remission

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

scholarly journals ECCO Position Paper: Harmonization of the Approach to Ulcerative Colitis Histopathology

2020 ◽  
Vol 14 (11) ◽  
pp. 1503-1511 ◽  
Author(s):  
Fernando Magro ◽  
Glen Doherty ◽  
Laurent Peyrin-Biroulet ◽  
Magali Svrcek ◽  
Paula Borralho ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Remission ◽  
Scoring Systems ◽  
Processing Technique ◽  
Histological Changes ◽  
Minimum Requirement ◽  
Histological Activity ◽  
Histological Remission ◽  
Definition Of ◽  
Consensus Expert

Abstract Currently, the main targets of drug therapy for ulcerative colitis [UC] are endoscopic and clinical remission. However, there is active discussion about the additional advantages of including histological remission as a target. Accumulating evidence indicates that microscopic activity persists in endoscopically quiescent UC, that histological changes may lag behind clinical remission after treatment, and that absence of histological activity predicts lower rates of relapse, hospitalization, surgery and subsequent neoplasia. Obtaining useful information from mucosal biopsies in this setting depends on accurate and consistent evaluation of histological features. However, there is no standardization of biopsy procedures, histological sample processing technique or histological scoring systems, and there is no agreement on the definitions of histological remission, response or activity. Accordingly, a consensus expert panel convened by the European Crohn’s and Colitis Organisation [ECCO] reviewed the literature and agreed a number of position statements regarding harmonization of UC histopathology. The objective was to provide evidence-based guidance for the standardization and harmonization of procedures, definitions and scoring systems for histology in UC, and to reach expert consensus where possible. We propose the absence of intraepithelial neutrophils, erosion and ulceration as a minimum requirement for the definition of histological remission. For randomized control trials we recommend the use of the Robarts histopathology index [RHI] or the Nancy index [NI]. For observational studies or in clinical practice we recommend the use of the NI. To predict the risk of future neoplasia in UC, cumulative histological scores over time are more useful than single scores.

scholarly journals Diet Diversity in Carnivorous Terebrid Snails Is Tied to the Presence and Absence of a Venom Gland

Toxins ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 108
Author(s):  
Juliette Gorson ◽  
Giulia Fassio ◽  
Emily S. Lau ◽  
Mandë Holford
Keyword(s):  
Venom Gland ◽  
Molecular Study ◽  
Strongly Correlated ◽  
Animal Evolution ◽  
Diet Diversity ◽  
Dietary Breadth ◽  
Venom Composition ◽  
Marine Snails ◽  
Predatory Strategy ◽  
Definition Of

Predator-prey interactions are thought to play a driving role in animal evolution, especially for groups that have developed venom as their predatory strategy. However, how the diet of venomous animals influences the composition of venom arsenals remains uncertain. Two prevailing hypotheses to explain the relationship between diet and venom composition focus on prey preference and the types of compounds in venom, and a positive correlation between dietary breadth and the number of compounds in venom. Here, we examined venom complexity, phylogenetic relationship, collection depth, and biogeography of the Terebridae (auger snails) to determine if repeated innovations in terebrid foregut anatomy and venom composition correspond to diet variation. We performed the first molecular study of the diet of terebrid marine snails by metabarcoding the gut content of 71 terebrid specimens from 17 species. Our results suggest that the presence or absence of a venom gland is strongly correlated with dietary breadth. Specifically, terebrid species without a venom gland displayed greater diversity in their diet. Additionally, we propose a revision of the definition of venom complexity in conoidean snails to more accurately capture the breadth of ecological influences. These findings suggest that prey diet is an important factor in terebrid venom evolution and diversification and further investigations of other understudied organisms, like terebrids, are needed to develop robust hypotheses in this area.

Abstract P533: Incidence and Outcomes of Thrombectomy Rescue Therapies in Acute Basilar Artery Occlusions

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Ronda Lun ◽  
Greg B Walker ◽  
David Weisenburger-Lile ◽  
Bertrand Lapergue ◽  
Adrien Guenego ◽  
...  
Keyword(s):  
Primary Outcome ◽  
Secondary Analysis ◽  
Hematoma Expansion ◽  
Primary Analysis ◽  
Predictive Values ◽  
Previous Definition ◽  
Secondary Analyses ◽  
Revised Definitions ◽  
Definition Of ◽  
Sensitivity Specificity

Background: Hematoma expansion (HE) is an important therapeutic target in intracerebral hemorrhage. Recently proposed HE definitions have not been validated, and no previous definition has accounted for withdrawal of care (WOC). Objective: To compare conventional and revised definitions of hematoma expansion (HE), while accounting for WOC. Methods: We analyzed data from the ATACH-2 trial, comparing revised definitions of HE incorporating intraventricular hemorrhage (IVH) expansion to the conventional definition of “≥6 mL or ≥33%”. The primary outcome was modified Rankin Scale of 4-6 at 90-days. We calculated the incidence, sensitivity, specificity, positive and negative predictive values, and c- statistic for all definitions of HE. Definitions were compared using non-parametric methods. Secondary analyses were performed after removing patients who experienced WOC. Results: Primary analysis included 948 patients. Using the conventional definition, the sensitivity was 37.1% and specificity was 83.2% for the primary outcome. Sensitivity improved with all three revised definitions (53.3%, 48.7%, and 45.3%, respectively), with minimal change to specificity (78.4%, 80.5%, and 81.0%, respectively). The greatest improvement was seen with the definition “≥6 mL or ≥33% or any IVH”, with increased c -statistic from 60.2% to 65.9% (p < 0.001). Secondary analysis excluded 46 participants who experienced WOC. The revised definitions outperformed the conventional definition in this population as well, with the greatest improvement in c -statistic using “≥6 mL or ≥33% or any IVH” (58.1% vs 64.1%, p < 0.001). Conclusions: HE definitions incorporating intraventricular expansion outperformed conventional definitions for predicting poor outcome, even after accounting for care limitations.

scholarly journals Parathormone Levels in a Middle-Eastern Healthy Population Using 2nd and 3rd Generation PTH Assays

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Marie-Hélène Gannagé-Yared ◽  
Marie-Noëlle Kallas-Chémaly ◽  
Ghassan Sleilaty
Keyword(s):  
Vitamin D ◽  
Healthy Subjects ◽  
Reference Range ◽  
Middle Eastern ◽  
Healthy Population ◽  
Strongly Correlated ◽  
Limits Of Agreement ◽  
25 Oh Vitamin D ◽  
D Values ◽  
Normal Calcium

Background. The purpose of the current study is to determine PTH reference values in vitamin-D-replete Lebanese adults using 2nd and 3rd generation PTH assays and to look at the factors that affect PTH variations. Methods. Fasting PTH was measured using 2nd and 3rd generation Diasorin PTH assays in 339 vitamin-D-replete healthy subjects aged 18 to 63 years (230 men and 109 women) who have normal calcium levels and an eGFR ≥60 ml/mn. 25-OH vitamin D (25(OH)D) was measured using the Diasorin assay. Results. For the 2nd PTH generation, median (IQR) levels were 48.9 (34.9–66.0) pg/ml, and its 2.5th–97.5th percentile values were 19.7–110.5 pg/ml for 25(OH)D values between 20 and 30 ng/ml, and 19.7–110.7 pg/ml for 25(OH)D values ≥30 ng/ml. For the 3rd PTH generation, the median (IQR) values were 23.9 (17.7–30.5) pg/ml, and its 2.5th–97.5th percentile values were, respectively, 9.2 and 50.2 pg/ml for 25(OH)D values between 20 and 30 ng/ml, and 8.4 and 45.4 pg/ml for 25(OH)D values ≥30 ng/ml. The median (IQR) serum 25(OH)D levels were 27.5 (23.8–32.7) ng/ml. 2nd and 3rd generation PTH values are strongly correlated (r = 0.96, p<0.0001), but poorly concordant (Lin’s concordance coefficient 0.365, 95% CI: 0.328–0.401) with observations beyond the 95% Bland–Altman limits of agreement. 2nd and 3rd generation PTH levels did not differ according to gender and were significantly correlated with age but not with 25(OH)D and serum calcium levels. Conclusion. Lebanese adult healthy subjects have higher 2nd and 3rd generation PTH levels compared with the reference range provided by the manufacturer. The reference range was not influenced by changing the 25(OH)D cutoff. The clinical significance of the higher PTH levels in our population should be investigated.

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