Significant Inflammatory Activity Research Articles

Relationship Between Calcified Plaque Burden, Vascular Inflammation, and Plaque Vulnerability in Patients With Coronary Atherosclerosis

BackgroundCoronary artery calcification is an integral part of atherosclerosis. It has been suggested that early coronary artery calcification is associated with active inflammation, and advanced calcification forms as inflammation subsides. Inflammation is also an important factor in plaque vulnerability. However, the relationship between coronary artery calcium burden, vascular inflammation, and plaque vulnerability has not been fully investigated. ObjectivesThis study aimed to correlate calcified plaque burden (CPB) at the culprit lesion with vascular inflammation and plaque vulnerability. MethodsPatients with coronary artery disease who had both computed tomography angiography and optical coherence tomography were included. The authors divided the patients into 4 groups: 1 group without calcification at the culprit lesion; and 3 groups based on the CPB tertiles. CPB was calculated as calcified plaque volume divided by vessel volume in the culprit lesion. The authors compared pericoronary adipose tissue (PCAT) attenuation for vascular inflammation and optical coherence tomography–derived vulnerable features among the 4 groups. ResultsAmong 578 patients, the highest CPB tertile showed significantly lower PCAT attenuation of culprit vessel compared with the other groups. The prevalence of features of plaque vulnerability (including lipid-rich plaque, macrophage, and microvessel) was also lowest in the highest CPB tertile. In the patients with calcification, higher age, statin use, and lower PCAT attenuation were independently associated with CPB. ConclusionsGreater calcium burden is associated with a lower level of vascular inflammation and plaque vulnerability. A greater calcium burden may represent advanced stable plaque without significant inflammatory activity. (Massachusetts General Hospital and Tsuchiura Kyodo General Hospital Coronary Imaging Collaboration; NCT04523194)

Diagnostic accuracy of an uncorrected native T1 mapping sequence for liver fibrosis and inflammation in autoimmune hepatitis: a prospective study using histopathology as reference standard.

There is an unmet clinical need for non-invasive imaging biomarkers that could replace liver biopsy in the management of patients with autoimmune hepatitis (AIH). In this study, we sought to evaluate the diagnostic accuracy of a simple uncorrected, non-contrast T1 mapping for detecting fibrosis and inflammation in AIH patients using histopathology as a reference standard. Over 3years, 33 patients with AIH were prospectively studied using a multiparametric liver MRI protocol which included T1 mapping. Biopsies were performed up to 3months before imaging, and a standardized histopathological score for fibrosis (F0-F4) and inflammatory activity (PPA0-4) was used as a reference. Statistical analysis included independent t test, Mann-Whitney U-test, and ROC (receiver operating characteristic) analysis. T1 mapping values were significantly higher in patients with advanced fibrosis (F0-2 vs. F3-4; p < 0.015), significant fibrosis (F0-1 vs. F2-4; p < 0.005), and significant inflammatory activity (PPA 0-1 vs. PPA 2-4 p = 0.048). Moreover, the technique demonstrated a good diagnostic performance in detecting significant (AUC 0.856) and advanced fibrosis (AUC 0.835), as well as significant inflammatory activity (AUC 0.763). A rapid, simple, uncorrected, non-contrast T1 mapping sequence showed satisfactory diagnostic performance in comparison with histopathology for detecting significant tissue inflammation and fibrosis in AIH patients, being a potential non-invasive imaging biomarker for monitoring disease activity in such individuals.

Accuracy of controlled attenuation parameter measurement for the detection of steatosis in autoimmune liver diseases

Concurrent fatty liver disease represents an emerging challenge in the care of individuals with autoimmune liver diseases (AILD). Therefore, we aimed to validate the ultrasound-based method of controlled-attenuation parameter (CAP) as a non-invasive tool to detect hepatic steatosis in individuals with AILD. The diagnostic performance of CAP to determine biopsy-proven hepatic steatosis (>5%) was assessed in individuals with AILD (autoimmune hepatitis [AIH], primary biliary cholangitis [PBC], primary biliary cholangitis [PSC], or variant syndromes) who underwent liver biopsy at the University Medical Center Hamburg-Eppendorf between 2015-2020 by calculating the area under the receiver operating characteristic (AUROC) curves. In AIH, the impact of disease activity was evaluated by assessment of CAP upon resolution of hepatic inflammation during follow-up. Overall, 433 individuals with AILD (AIH: 218, PBC: 51, PSC: 85, PBC/AIH: 63, PSC/AIH: 16) were included. Histologically proven steatosis was present in 90 individuals (20.8%). Steatosis was less frequently observed in people with PSC (14%) than in other AILD. CAP values correlated positively with grade of steatosis (ρ= 0.39) and the BMI (ρ= 0.53). In PBC and PSC, the ROC curves defined an AUROC of 0.81 and 0.93 for detecting steatosis at an optimal cut-off of 276dB/m (sensitivity: 0.71; specificity: 0.82) and 254dB/m (sensitivity: 0.91, specificity: 0.85), respectively. In AIH, the diagnostic performance of CAP was significantly lower (AUROC= 0.72, p= 0.009). However, resolution of hepatic inflammation under treatment was associated with a significant increase in CAP levels (median [IQR]:+38.0 [6-81] dB/m) and considerably improved diagnostic accuracy (AUROC= 0.85; cut-off: 288dB/m; sensitivity: 0.67, specificity: 0.90). In PBC and PSC, hepatic steatosis can be reliably detected by applying disease-specific thresholds of CAP. In AIH, the diagnostic accuracy of CAP is moderate at diagnosis, but improves after acute hepatitis has resolved. Non-invasive estimation of fat content in the liver can be performed with the ultrasound-based method of controlled-attenuation parameter (CAP). Here, we showed that the presence of a concomitant fatty liver is frequent in people with autoimmune liver diseases and we determined disease-specific thresholds of CAP to best predict the presence of a fatty liver. CAP measurement was shown to be a valid tool to detect fatty liver in individuals with PSC and PBC; however, in AIH, CAP had limited accuracy especially when significant inflammatory activity was present in the liver. In the context of substantial liver inflammation, therefore, CAP values should be interpreted with caution, and measurements should be repeated after acute hepatitis has resolved.

Extra-articular manifestations of rheumatoid arthritis remain a major challenge: data from a large, multi-centric cohort

IntroductionAlthough Rheumatoid Arthritis (RA) extra-articular manifestations (ExtRA) occurrence has been decreasing over time, they are still a major mortality risk factor for patients.ObjectiveTo determine the prevalence of ExtRA in a large cohort, and its association with demographic and clinical variables.MethodCross-sectional and observational study, based on a multi-centric database from a prospective cohort, in which 11 public rheumatology centres enrolled RA patients (1987 ARA or 2010 ACR-EULAR). Data collection began in 08-2015, using a single online electronic medical record. Continuous variables were compared using Mann–Whitney U-test, and Fisher’s exact test or chi-square test, as appropriate, were used for categorical variables. The level of significance was set at 5% (p < 0.05).Results1115 patients were included: 89% women, age [mean ± SD] 58.2 ± 11.5 years, disease duration 14.5 ± 12.2 years, positive Rheumatoid Factor (RF, n = 1108) in 77%, positive anti-cyclic citrullinated peptide (ACPA, n = 477) in 78%. Regarding ExtRA, 334 occurrences were registered in 261 patients, resulting in an overall prevalence of 23.4% in the cohort. The comparison among ExtRA and Non-ExtRA groups shows significant higher age (p < 0.001), disease duration (p < 0.001), RF high titers (p = 0.018), Clinical Disease Activity index (CDAI) (p < 0.001), Disease Activity Index 28 (DAS 28) (p < 0.001), and Health Assessment Questionnaire (HAQ) (p < 0.001) in ExtRA group. Treatment with Azathioprine (p = 0.002), Etanercept (p = 0.049) Glucocorticoids (GC) (‘p = 0.002), and non-steroidal anti-inflammatory drugs (NSAIDs) (p < 0.001) were more frequent in ExtRA group.ConclusionsExtRA manifestations still show an expressive occurrence that should not be underestimated. Our findings reinforce that long-term seropositive disease, associated with significant disability and persistent inflammatory activity are the key factors related to ExtRA development.

Acute Bone Loss and Infrapatellar Fat Pad Fibrosis in the Knee After an In Vivo ACL Injury in Adolescent Mice

Background: Young patients are 6 times more likely than adults to have a primary anterior cruciate ligament (ACL) graft failure. Biological factors (ie, tunnel osteolysis) may account for up to a third of these failures. Previous evaluations of patient ACL explants indicated significant bone loss within the entheseal regions. However, it remains unknown if the degree of bone loss within the ACL insertion regions, wherein ACL grafts are fixated, exceeds that of the femoral and tibial condylar bone. Hypothesis: Bone loss in the mineralized matrices of the femoral and tibial ACL entheses is distinct from that clinically reported across the whole knee after injury. Study Design: Controlled laboratory study. Methods: We developed a clinically relevant in vivo mouse ACL injury model to cross-sectionally track the morphological and physiological postinjury changes within the ACL, femoral and tibial entheses, synovial joint space, and load-bearing epiphyseal cortical and trabecular bone components of the knee joint. Right ACLs of 10-week-old C57BL/6J female mice (N = 75) were injured in vivo with the contralateral ACLs serving as controls. Mice were euthanized at 1, 3, 7, 14, or 28 days after injury (n = 12/cohort). Downstream analyses included volumetric cortical and trabecular bone analyses and histopathologic assessments of the knee joint after injury. Gait analyses across all time points were also performed (n = 15 mice). Results: The majority of the ACL injuries in mice were partial tears. The femoral and tibial cortical bone volumes were 39% and 32% lower, respectively, at 28 days after injury than those of the uninjured contralateral knees (P < .01). Trabecular bone measures demonstrated little difference between injured and control knees after injury. Across all bone measures, bone loss was similar between the injured knee condyles and ACL entheses. There was also significant inflammatory activity within the knee after injury. By 7 days after injury, synovitis and fibrosis were sigificantly elevated in the injured knee compared with the controls (P < .01), which corresponded with significantly higher osteoclast activity in bone at this time point compared with the controls. This inflammatory response signficantly persisted throughout the duration of the study (P < .01). The hindlimb gait after injury deviated from normal, but mice habitually loaded their injured knee throughout the study. Conclusion: Bone loss was acute and persisted for 4 weeks after injury in mice. However, the authors’ hypothesis was not confirmed, as bone quality was not significantly lower in the entheses compared with the condylar bone regions after injury. With relatively normal hindlimb loading but a significant physiological response after injury, bone loss in this model may be driven by inflammation. Clinical Relevance: There is persistent bone resorption and fibrotic tissue development after injury that is not resolved. Inflammatory and catabolic activity may have a significant role in the postinjury decline of bone quality in the knee.

Characteristics and Factors Associated with Inflammatory Activity on Liver Biopsy in Autoimmune Hepatitis Patients Aged 50 Years or Older

Introduction: Autoimmune hepatitis is an inflammatory liver disorder histologically characterized by portal lymphoplasmocytic hepatitis with interface activity and lobular inflammation.&#x0D; Aims: To identify clinical characteristics associated with older age and also to pinpoint clinical characteristics associated with significant inflammation in liver histology.&#x0D; Methods: Cross-sectional analytical study that evaluated medical records of adult patients with autoimmune hepatitis seen at the Gastroenterology and Hepatology Outward of a Tertiary University Hospital. Bivariate analysis was performed to identify the characteristics associated with age equal or greater than 50 years and the significant histological inflammatory activity.&#x0D; Results: Forty-seven patients were included, with their mean age of 42.8±16.0 (43.0) years. Furthermore, 80.9% of them were women, 31.9% were 50 years-old or older. Thirty-one patients were submitted to liver biopsy and 29.0% presented significant inflammation. When compared in terms of age, individuals equal or higher 50 years old presented higher medians of GGT (129 vs. 282 U/L; P = 0.034) and a higher proportion of significant inflammation (50 vs. 6.7%; P = 0,024). Patients with significant inflammation on the liver biopsy presented a higher mean age (63.7±14.0 vs. 41.0±14.4; P = 0.001), and a greater proportion of patients equal or above 50 years old (85.7% vs. 66.7%; P=0.024) than individuals with mild inflammation.&#x0D; Conclusions: Individuals equal or higher 50 years old presented higher medians of GGT levels and a greater proportion of significant inflammation on liver histology.

Histologic changes in immune-tolerant patients with chronic hepatitis B: a systematic review and meta-analysis

The serological diagnostic criteria for the immune-tolerant (IT) phase have not been strictly defined and it is hard to determine an accurate rate for significant histologic changes among IT patients. The aim of this study was to establish a baseline rate of significant histologic changes and to determine the main characteristics of IT patients. We systematically searched PubMed, Embase, and Web of Science. Studies reporting liver biopsy results (inflammation grade or fibrosis stage) for adults with chronic hepatitis B virus (HBV) infection in the IT phase diagnosed by serological criterion were included to pool the rate of significant histologic changes. Studies that enrolled subjects with confirmed chronic HBV infection in the IT phase diagnosed by serological and liver biopsy criteria (dual criteria) were included to pool the mean values of main characteristics among IT patients. Of 319 studies screened, 15 were eventually included in the meta-analysis. The pooled rates of significant liver fibrosis and inflammatory activity for 10 studies were 10% (95% confidence interval [CI] 0.06–0.18) and 16% (95% CI 0.07–0.31), respectively. The pooled mean values of age, alanine aminotransferase level, HBV DNA level, and HBsAg level for another 5 studies with IT patients diagnosed by dual criteria were 30.7 years (95% CI 27.31–34.09), 26.64 IU/mL (95% CI 24.45–28.83), 8.41 log10 cp/mL (95% CI 7.59–9.23), and 4.24 log10 IU/mL (95% CI 3.67–4.82), respectively. Significant histologic changes were not rare events among IT patients. Strictly defined serological diagnostic criteria for the IT phase are warranted.

P198 The role of comorbidities alongside patient and disease characteristics on long-term disease activity in RA using UK inception cohort data

Abstract Background/Aims Control of disease activity in Rheumatoid Arthritis (RA) is crucial to prevent long-term joint damage and disability. European Alliance of Associations for Rheumatology (EULAR) guidelines recommend focus on disease activity when measuring health outcomes in people living with RA. Particularly, one of their four overarching principles targets clinical remission, defined as the absence of significant inflammatory disease activity, or low disease activity an acceptable alternative. In EULAR’s most recent guidelines (2014), attention was drawn to the role of comorbidities in RA disease management noting the “potential to preclude treatment intensification”. Besides this, recent work by the EULAR Task Force on difficult-to-treat RA recognises that comorbidities can influence the assessment of inflammatory activity in individuals with RA. This study aimed to identify early predictors of poor disease activity at five and 10 years, focussing on comorbidities alongside clinical/sociodemographic factors at first presentation. Methods Patients were recruited from two UK-based RA cohorts; Early Rheumatoid Arthritis Study (ERAS, 1986-2001) and Early Rheumatoid Arthritis Network (ERAN, 2002-2012). Participants were classified into two groups; low (&amp;lt;3.2) and moderate/high (≥3.2) Disease Activity Score (DAS28) at 5/10 years. Clinical information (e.g., rheumatoid nodules, erosions), sociodemographic factors (e.g., ethnicity, deprivation) and comorbidity burden (measured using the Rheumatic Diseases Comorbidity Index [RDCI]) were recorded at baseline and yearly thereafter. Multivariable logistic regression models (outcome; low versus DAS28≥3.2) were fitted using multiple imputation. Results 2,701 patients with RA were recruited (mean age 56.1 years, 66.9% female); 5-year follow-up data were available for 1,718 (63.4%) and 10-year for 820 (30.4%) patients. A higher proportion of individuals had DAS28≥3.2 values at 10 years than five (65.6% vs 59.7%). In multivariable analyses, baseline RDCI was not associated with DAS28 at five (OR 1.05, 95% CI 0.91 to 1.22) or 10 years (OR 0.99, 95% CI 0.75 to 1.31). Sociodemographic factors (female gender, worse deprivation) and poorer baseline HAQ were associated with DAS28≥3.2 at both timepoints, with no association found with age at onset. Being seropositive was associated with DAS28≥3.2 at 5 but not 10 years of follow-up. Conversely, a relationship existed between presence of erosions at baseline and 10-year DAS28 (OR 1.82, 95% CI 1.16 to 2.85). Conclusion This study found no association between baseline comorbidity burden and long-term RA disease activity. However, in models adjusted for comorbidity burden, associations with sociodemographic and clinical factors were demonstrated. These results build upon those relating to functional outcome and will accelerate the identification of those RA patients at increased risk of worse outcomes at initial rheumatology appointment. Additionally, these findings suggest that tailored intervention can be implemented in a timely manner, in line with national and international recommendations, potentially limiting permanent joint damage and disability to improve quality of life for individuals with RA. Disclosure A.D. Busby: None. J. Wason: None. A.G. Pratt: None. A. Young: None. J. Isaacs: None. E. Nikiphorou: None.

Resolvins' Obesity-Driven Deficiency: The Implications for Maternal-Fetal Health.

Since pregnancy is already characterized by mild but significant inflammatory activity in physiological conditions, when complicated by obesity the probability of a persistent inflammatory state increases, with consequent multiple repercussions that add up to the complications associated with acute inflammation. In this context, the role of resolvins, specialized pro-resolving mediators (SPMs), deriving from omega-3 essential fatty acids, may be crucial. Indeed, differential production in numerous high-risk conditions associated with both childbirth and neonatal health, the correlation between maternal omega-3 intake and resolvin concentrations in maternal blood and at the placental level, and the high values found in breast milk in the first month of breastfeeding, are some of the most important hallmarks of these autacoids. In addition, a growing body of scientific evidence supports the lack of SPMs, at the level of immune-metabolic tissues, in the case of obesity. Furthermore, the obesity-related lack of SPMs seems to be decisive in the context of the current outbreak of COVID-19, as it appears to be one of the causes associated with the higher incidence of complications and negative outcomes of SARS-CoV-2 infection. The usefulness of metabolomics in this field appears clear, given that through the metabolome it is possible to observe the numerous and complex interactions between the mother, the placenta and the fetus in order to identify specific biomarkers useful in the prediction, diagnosis and monitoring of the various obstetric conditions. However, further investigations are needed in order to evaluate the possible use of some resolvins as biomarkers of maternal–fetal outcomes but also to establish adequate integration values in pregnant women with omega-3 fatty acids or with more active derivatives that guarantee optimal SPM production under risky conditions.

Synthesis, Molecular Docking and In Vivo Biological Evaluation of Iminostilbene Linked 1,2,3-Triazole Pharmacophores as Promising Anti- Anxiety and Anti-Inflammatory Agents.

Iminostilbene and 1,2,3-triazole ring containing compounds are considered as beneficial substrates in drug design. This study was aimed at the synthesis of novel series of iminostilbene linked 1,2,3- triazole pharmacophores (7c-n) by Cu(I) catalyzed 1,3 dipolar cycloaddition reaction between 5- (Prop-2-yn-1-yl)-5H-dibenzo[b,f]azepine (7b) and various substituted azidobenzene derivatives (3cn). The chemical structures of compounds were confirmed by 1H NMR, 13C NMR, LC-MS and molecular docking studies were carried out through HEX docking software. The in vivo anti anxiety capacity of the compounds was evaluated by using "elevated plus maze" (EPM), anxiety model. The results exhibited that compounds (7d, 7e, 7j and 7k) have a higher anti anxiety effect close to diazepam. The anti-inflammatory activities of the synthesized compounds were evaluated by "Carrageenan-induced rat paw edema" model, compounds (7b, 7c, 7d, 7f, and 7j) demonstrated statistically significant inflammatory activity. Molecular docking analysis revealed that compounds (7d, 7e and 7j) bound to GABA(A) proteins show more efficiency when compared to the other analogues in the series. These results suggest that compounds (7b, 7c, 7d, 7e, 7f, and 7j) can be considered as novel candidates for anti-anxiety and anti-inflammatory agents. Moreover, docking method was used to elucidate anti-anxiety effect of compounds. This study furnished insight into the molecular interactions of synthesized compounds with their physiological targets, and the potential to develop bioactive heterocyclic compounds.

P205 Eliakim and CECDAIic scores are useful pan-intestinal tools for CD diagnosis and activity monitoring

Abstract Background Capsule endoscopy is a valuable tool in the diagnosis and monitoring of Crohn’s disease (CD). Recently, a new panenteric capsule (pan-CE), PillCam Crohn’s (Medtronic, USA) was approved. A novel quantitative score of inflammation for PillCam Crohn’s, the Eliakim score, has emerged. However, the optimal index for panenteric monitoring disease activity is far from being completely defined. We aimed to evaluate the correlation and accuracy between the pan-CE Eliakim and capsule endoscopy Crohn’s disease activity index (CECDAIic) scores and inflammatory parameters. Methods Retrospective study, including a cohort of consecutive patients with suspected or established CD that underwent Pan-CE PillCam Crohn’s over 4 years. The Eliakim and CECDAIic scores were calculated. Spearman correlation (rs) was used to access the correlation between the scores and inflammatory biomarkers. Results Thirty-two patients were included, 71.9% females, with mean age of 35±13 years, 59.4% with suspected CD. The median Eliakim and CECDAIic scores were 5.5 (0–13) and 6.5 (0–15.5), respectively. The diagnosis of CD was established in 31.6% of patients with suspected CD. We found a very good correlation between Eliakim and CECDAIic scores (rs=0.87; p&amp;lt;0.001), and a moderate correlation between Eliakim and CECDAIic scores with C-reactive protein (rs=0.53; p=0.003), (rs=0.44; p=0.02), and fecal calprotectin (rs=0.46; p=0.02), (rs=0.54; p=0.01), respectively. In patients with suspected CD, an Eliakim ≥3.5 and CECDAIic score ≥5.5 had a sensitivity of 100%, and specificity of 84.6%, and 75.0%, respectively, for the diagnosis of CD. Conclusion The Eliakim and CECDAIic scores have a strong correlation in assessing panenteric CD activity, and a moderate correlation with inflammatory biomarkers. The application of Eliakim ≥3.5 and CECDAIic score ≥5.5 as the cutoff values for the presence of significant inflammatory activity in patients undergoing pan-CE for suspected CD may be useful to establish the diagnosis.

Detection of SARS-CoV-2 virus using an alternative molecular method and evaluation of biochemical, hematological, inflammatory, and oxidative stress in healthcare professionals

In early December 2019, an outbreak of coronavirus disease 2019 caused by a new strain of coronavirus (SARS-CoV-2), occurred in the city of Wuhan, Hubei Province, China. On January 30, 2020, the World Health Organization (WHO) declared the outbreak a public health emergency of international concern. Since then, frontline healthcare professionals have been experiencing extremely stressful situations and damage to their physical and mental health. These adverse conditions cause stress and biochemical, hematological, and inflammatory changes, as well as oxidative damage, and could be potentially detrimental to the health of the individual. The study population consisted of frontline health professionals working in BHU in a city in southern Brazil. Among the 45 participants, two were infected with the SARS-CoV-2 virus and were diagnosed using immunochromatographic tests such as salivary RT-LAMP and qRT-PCR. We also evaluated biochemical, hematological, inflammatory, and oxidative stress markers in the participants. The infected professionals (CoV-2-Prof) showed a significant increase in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholesterol, lactic dehydrogenase, lymphocytes, and monocytes. In this group, the levels of uric acid, triglycerides, leukocytes, neutrophils, hemoglobin, hematocrit, and platelets decreased. In the group of uninfected professionals (NoCoV-2-Prof), significant increase in HDL levels and the percentages of eosinophils and monocytes, was observed. Further, in this group, uric acid, LDH, triglyceride, and cholesterol levels, and the hematocrit count and mean corpuscular volume were significantly reduced. Both groups showed significant inflammatory activity with changes in the levels of C-reactive protein and mucoprotein. The NoCoV-2-Prof group showed significantly elevated plasma cortisol levels. To our kowledge, this study is the first to report the use of the RT-LAMP method with the saliva samples of health professionals, to evalute of SARS-CoV-2.

Colonic Bluish–Black Patches in a 57-Year-Old Woman with Crohn’s Disease

Question: A 57-year-old woman with a past history of aplastic anemia was diagnosed with Crohn’s disease, Montreal A3, L3, B1, in September 2015. The initial endoscopic examination revealed multiple ulcers over the terminal ileum, ileocecal valve, and proximal ascending colon. She received oral mesalazine 4 g/d and prednisolone 2.5–15.0 mg/d during the first year after diagnosis, but did not respond to the treatment; she continued to experience right lower quadrate abdominal pain and intermittent bloody diarrhea. A follow-up colonoscopy showed progressive ulcers over the terminal ileum and ileocecal valve in July 2016. Given her history of aplastic anemia and sepsis, she hesitated to take azathioprine, methotrexate, or tumor necrosis factor inhibitors. Instead, she started taking indigo naturalis (Qing-Dai) 4.5 g/d in December 2016. She achieved steroid-free clinical remission under the treatment with mesalazine and indigo naturalis. However, a follow-up colonoscopy still revealed a 1.5-cm ulcer over the ileocecal valve in November 2018. In addition, we observed multiple discrete or coalescing irregularly shaped, bluish–black patches from the ileocecal valve to the rectum with a haphazard distribution, reminiscent of the skin markings of Holstein Friesian cattle (Figure A). A colonic biopsy was obtained, and a representative hematoxylin and eosin stain is shown (Figure B). What is the diagnosis? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Histology of the discolored colonic lesion revealed scattered pigment-laden histiocytes in the lamina propria and submucosa. Higher magnification disclosed bluish, needle-like crystals in the cytoplasm of these histiocytes. In light of the presence of pigment-laden histiocytes, we called the lesions indigo naturalis-related pseudomelanosis. Unlike melanosis coli, which typically shows continuous homogeneous brown or black discoloration of colon mucosa (snake-skin appearance or starry sky appearance), indigo naturalis-related pseudomelanosis exhibits a haphazard distribution of black discoloration reminiscent of the skin markings of Holstein Friesian cattle.1Freeman H.J. “Melanosis” in the small and large intestine.World J Gastroenterol. 2008; 14: 4296-4299Crossref PubMed Scopus (43) Google Scholar Microscopically, melanosis coli is characterized by the deposition of lipofuscin in histiocytes, and deposition of bluish needle-like crystals is noted in indigo naturalis-related pseudomelanosis.2Kimber R.D. Roberts-Thomson I.C. Gastrointestinal: melanosis coli.J Gastroenterol Hepatol. 1999; 14: 1047Crossref PubMed Scopus (6) Google Scholar The distribution of discolored mucosa did not correlate with inflammatory activity, which was most severe over the terminal ileum and ileocecal valve. This finding implies that the absorption of indigo naturalis occurred not only at the inflammatory sites, but also over normal colon mucosa. It remains to be seen whether deposition of indigo naturalis has any long-term adverse effect, although histologically the mucosa with indigo deposition was not accompanied by significant inflammatory activity.

Briarenols W-Z: Chlorine-Containing Polyoxygenated Briaranes from Octocoral Briareum stechei (Kükenthal, 1908).

Briareum stechei is proven to be a rich source of 3,8-cyclized cembranoids (briarane) with a bicyclo[8.4.0] carbon core. In the present study, four previously unreported briaranes, briarenols W–Z (1–4), along with solenolide A (5), briarenolide M (6), briaexcavatolide F (7), and brianolide (8), were isolated and characterized through spectroscopic analysis, and the absolute configuration of 8 was corroborated by a single-crystal x-ray diffraction analysis. Briaranes 2 and 5 were found to induce significant inflammatory activity in lipopolysaccharide (LPS)-induced RAW 264.7 mouse macrophage cells by enhancing the expression of the inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins.

Role of epicardial adipose tissue in the development of atrial fibrillation in hypertensive patients

Obesity is a progressing epidemic, the prevalence of which has doubled over the past 30 years. The distribution of adipose tissue is an important factor in predicting the risk of cardiovascular events. The most significant inflammatory activity is characteristic of epicardial adipose tissue (EAT), the role of which in the development of atrial fibrillation (AF) remains a subject of discussion.Aim. To study the effect of EAT size on the development of AF in hypertensive (HTN) patients.Material and methods. The study included 95 patients with HTN aged 38-72 years (mean age, 61,5±1,8 years), including 45 patients with paroxysmal AF (group I) and 50 patients in the comparison group (group II). In order to assess the severity of visceral obesity, all patients underwent a general examination and echocardiography. To determine the EAT volume, cardiac multislice computed tomography was performed.Results. Echocardiography revealed that the EAT thickness was significantly greater in hypertensive patients with paroxysmal AF than in the comparison group: 11,6±0,8 and 8,6±0,4 mm, respectively (p&lt;0,001). According to cardiac multislice computed tomography, a significant increase in EAT volume was revealed in patients of group I (4,6±0,4 ml) compared with group II (3,5±0,25 ml) (p=0,019). In hypertensive patients with paroxysmal AF, a positive moderate relationship between the EAT volume and left atrial volume was revealed (r=0,7, p=0,022). Multivariate analysis showed that in hypertensive patients, EAT thickness &gt;10 mm and volume &gt;6 ml can serve as integral markers of the onset of paroxysmal AF.Conclusion. Integral markers of AF in hypertensive patients are an increase in the EAT thickness &gt;10 mm (odds ratio, 4,1; 95% confidence interval, 1,1-5,6) and volume &gt;6 ml (odds ratio 3,7; 95%, confidence interval 1,0-4,2).

Very low probability of significant liver inflammation in chronic hepatitis B patients with low ALT levels in the absence of liver fibrosis.

SummaryBackgroundGuidelines recommend liver biopsy to rule out significant inflammatory activity in chronic hepatitis B (CHB) patients with elevated hepatitis B virus (HBV) DNA but without other indications for treatment.AimTo study rates and determinants of clinically significant liver inflammation.MethodsWe selected patients with HBV DNA > 2000 IU/mL from the SONIC‐B database. The presence of significant inflammation (METAVIR ≥ A2 or HAI ≥ 9) was assessed by liver biopsy and correlated with alanine aminotransferase (ALT) levels (according to AASLD upper limits of normal [ULN]) and stratified by the presence of significant liver fibrosis (Ishak ≥ 3 or METAVIR ≥ F2).ResultsThe cohort included 2991 patients; 1672 were HBeAg‐positive. ALT was < ULN in 270 (9%), 1‐2 times ULN in 852 (29%) and > 2 times ULN in 1869 (63%). Significant fibrosis was found in 1419 (47%) and significant inflammatory activity in 630 (21%). Significant inflammatory activity was found in 34% of patients with liver fibrosis, compared to 9.5% of those without (P < 0.001). Among patients without fibrosis, significant inflammatory activity was detected in 3.6% of those with normal ALT, 5.0% of those with ALT 1‐2 times ULN and in 13% of those with ALT > 2 times ULN (P < 0.001). ALT < 2 times ULN had a negative predictive value of 95% for ruling out significant inflammatory activity among patients without liver fibrosis.ConclusionsAmong patients without significant fibrosis, an ALT level < 2 times ULN is associated with < 5% probability of significant inflammatory activity. If fibrosis can be ruled out using non‐invasive methods, liver biopsy solely to assess inflammatory activity should be discouraged.

Simplify to improve in capsule endoscopy – TOP 100 is a swift and reliable evaluation tool for the small bowel inflammatory activity in Crohn’s disease

Background: Capsule endoscopy is a widely recognized method to study the small bowel, including in patients with Crohn’s disease (CD). The Lewis score (LS) is a valuable tool in this setting, able to assess inflammatory activity. TOP100, a new software tool of the RAPID Reader®, emerged to assist in the time-consuming capsule reading process, by automatically selecting 100 images that will most likely contain abnormalities.Aim: Evaluate the agreement between TOP100 and classic reading (CR) in determining LS in the setting of CD.Methods: Retrospective study including consecutive patients undergoing small bowel capsule endoscopy (SBCE) for suspected or established CD. One experienced reader performed CR and calculated the LS. Another experienced reader, blinded to the CR results, reviewed all SBCE videos using TOP100 and calculated the LS.Results: One hundred and fifteen patients were included. SBCE detected significant inflammatory activity (LS ≥135) in 64 patients (55.7%). We verified a strong agreement between the two methods of capsule reading (Kappa = 0.83, p < .001), with an agreement on 89.6% of the cases. The agreement was superior in moderate-to-severe inflammatory activity (Kappa = 0.92, p < .001). All cases of moderate-to-severe activity detected by CR were identified by TOP100 as significant inflammatory activity. A good agreement was verified in all tertiles (p < .001).Conclusions: Although the classical review of the entire video remains the gold standard, the TOP100 has been shown to be a useful tool in assisting the reader in a prompt calculation of LS, in particular for identifying patients with moderate-to-severe inflammatory disease.

P727 Small bowel capsule endoscopy impact on therapeutic decisions in established Crohn’s disease: Analysis of a real-world data

Abstract Background Small bowel (SB) evaluation in established Crohn’s disease (eCD) is of paramount importance for planning therapy strategies. However, the utility of CE in helping physicians to make decisions in eCD is not currently well established. To investigate clinical impact of CE to assess activity and extension of eCD and to evaluate whether the results of CE modify therapeutic decisions. Methods We conducted a single centre retrospective cohort study. All consecutive adult’s patients submitted to CE for eCD were included from November 2012 to November 2018. Data on demography, previous research, medications for IBD and follow-up were analysed. Univariate analysis was carried out to identify CE features associated with changes in therapeutic management. Results A total of 329 CE protocols in adult′s patients were performed, of which 90 were in IBD. We included in the analysis 27 CEs submitted for eCD. The mean age was 35 years (range 15–75), 17 (63%) were males and median disease duration was 8 years. The CE reached the cecum in 26 cases (96%) and retention was observed in only one patient (4%) without necessity of surgical removal. At the time of CE, 5 patients (18%) had abnormal inflammatory biomarkers, anaemia in 4 (15%), abdominal pain in 18 (67%) and diarrhoea in 16 (59%). Thirteen of 27 patients (48%) had CE findings consistent with mucosal activity of CD. The lesions identified by CE included ulcers 11 (41%), erythema and villous enema 10 (37%), erosions 2 (7%), stenosis 2 (7%) and were distributed mainly in the distal part of the SB (3rd tertile) in 12 (44%), but in 4 (15%) the proximal SB (1st and 2nd tertile) was also affected. The mean Lewis Score (LS) was 784 (8–5392). Significant inflammatory activity (LS ≥ 135) was detected in 9 (33%) and was moderate or severe (LS &amp;gt; 790) in 2 (7%). CE has changed Montreal classification in 4 (15%) of patients and in 14 (52%) SB mucosal activity was ruled out. Indeed, CE has changed therapeutic management in 14 (52%) of patients within 3 months after the CE, as follows: 8 patients were started new biological therapy, 3 were optimised biological therapy, 2 were started on budesonide and 1 suspended azathioprine. Proximal SB affected, as compared with only distal SB affected, were more frequently associate with changes in therapeutic management (100% vs. 43%, p: 0.04). Significant inflammatory activity (LS ≥ 135), as compared with LS &amp;lt; 135, were also more frequently associate with changes in therapeutic management (82% vs. 25%, p: 0.004). Conclusion In our study, CE in patients with eCD added valuable clinical information and had a great impact on therapeutic decisions. Whether this approach will improve outcomes in eCD will require further investigation.

P232 In suspected small bowel Crohn’s disease: Clinical impact of using capsule endoscopy to make decisions

Abstract Background Capsule endoscopy (CE) can detect small bowel (SB) lesions compatible of Crohn’s disease (CD) in patients with suggestive symptoms but with inconclusive results for the diagnostic workup. However, the clinical impact of CE in helping physicians to make decisions about patients with suspected CD is not currently well established. The aim of the study was to investigate the clinical impact of CE to confirm diagnosis of CD and also to evaluate whether the results of CE modify therapeutic decisions. Methods We conducted a single-centre retrospective cohort study. All consecutive adult’s patients submitted to CE for clinical suspected of CD, on period November 2012 to November 2018, were included. Data on demography, previous research, medications for IBD, CE procedures and follow-up were analysed. Multivariate logistic regression analysis was carried out to identify predictors of CD. Results A total of 329 CE protocols in adult’s patients were performed over the study period. Ninety were in IBD patients and were included in the analysis 63 CEs submitted for suspected of CD: Clinical suspected CD 54(86%) and colitis unclassified 9 (14%). The mean age was 41 years (range 17–77 years) and 54% were males. The CE reached the caecum in 58 cases (92%) and retention was observed in 5 (8%) with only one patient (1.6%) requiring surgical removal. Overall, 28 of 63 patients (44%) had CE findings consistent with the diagnosis of CD. The lesions identified by CE included ulcers 24 (86%), erythema and villous oedema 17(61%), aphthas and mucosal erosions 5 (18%), stenosis 2 (7%) and were distributed mainly in the distal part of the SB (third tertile) in 23 (82%), but in 14 (50%) cases the proximal SB (first and second tertiles) was also affected. The mean Lewis Score (LS) was 903 (112–4356). Significant inflammatory activity (LS ≥ 135) was detected in 17 (27%) and was moderate or severe (LS &amp;gt; 790) in 7 (11%). CE visualise normal SB mucosa in 34 (54%) of patient’s, which rules out CD. Therapeutic started in 23 (36%) of patients, initiating a new IBD medication in most cases in the 3 months after the CE. On logistic regression analysis, male (p = 0.02) and findings in ileocolonoscopy (p = 0.004) were independents predictors of CD. Conclusion In our cohort, CE in suspected CD confirm diagnosis in 44% of cases. Male gender and findings in ileocolonoscopy appear to be independents predictors of CD. CE is a useful tool in suspected CD, since it adds relevant information for diagnosis and had a great impact on therapeutic decisions.

Lewis score: a useful tool for diagnosis and prognosis in Crohn's disease.

videocapsule endoscopy (VCE) is currently the most sensitive diagnostic tool to detect early small bowel inflammation. A Lewis score (LS) of ≥ 135 as the cutoff value for the presence of significant inflammatory activity in patients undergoing VCE for suspected Crohn's disease (CD) has been suggested as a useful tool for the diagnosis of CD. The aim of this study was to evaluate the diagnostic and prognostic accuracy of the LS in patients with suspected CD undergoing VCE. a retrospective single-center study was performed that included patients who underwent VCE for suspected CD between January 2010 and December 2015. Inflammatory activity was assessed with the LS. Patients were grouped according to the criteria of the International Conference on Capsule Endoscopy (ICCE) for the definition of suspected CD; group 1: patients not fulfilling ICCE and group 2: patients with ≥ 2 ICCE criteria. one hundred and ninety-one patients were included, 61% were female and the mean age was 39 ± 14 years. VCE detected significant inflammatory activity (LS ≥ 135) in 81 patients (42%); 24 patients from group 1 (32%) and 57 patients from group 2 (50%) (p = 0.014). During a mean follow-up period of 41 ± 21 months (12-79), a CD diagnosis was determined in 60 patients (31%); 55 patients with LS ≥ 135 (92%) and five patients with LS < 135 (5%) (p < 0.001). The LS showed a good diagnostic accuracy with an AUROC of 0.93 (p < 0.001). During the first year after diagnosis, there was a significant association between a higher LS and the need for immunomodulatory therapy, biological therapy, bowel resection surgery or hospital admission due to a CD flare-up. the LS (cutoff ≥ 135) is very useful in the diagnosis of CD in patients undergoing VCE. Moreover, higher values of this score was associated with prognostic variables.