Degree Of Histologic Inflammation Research Articles

P0064 Investigating a pathogenic role for IL-18 in Inflammatory Bowel Disease beyond the classical type 1 immunity paradigm

Abstract Background Crohn’s disease (CD) and ulcerative colitis (UC) are intestinal diseases driven by chronic reactivation of memory T helper (Thm) 1-like and Th17m cells, respectively. Disease remission remains difficult to achieve and maintain due to inter-patient heterogeneity in disease severity and underlying immune responses. Moreover, variations in the pathogenic Thm responses, the treatment target, are understudied. The proinflammatory cytokine IL-18 enhances IL-12-induced IFN-γ production by Th1 cells, as seen in Th1-driven inflammatory diseases. However, its potential pathogenic role in immune-mediated diseases, like CD and UC, is unclear. Upon investigating immune responses in therapy-naïve pediatric CD and UC patients, we detected increased IL-18 plasma concentrations that were correctable by therapy. We hypothesized that IL-18 plays a role in both CD and UC by stimulating Th1m but also Th17m cells, worsening disease. Methods We examined therapy-naïve pediatric CD and UC patient plasma proteomics (92 proteins, Proximity Extension Assay technology; CD: n=85, UC: n =31, control: n=25), circulating gut-homing Thm populations, transcriptomes of intestinal biopsies (CD: n=57, UC: n =21, control: n=12), and clinical disease parameters. Further, we assessed cytokine responses by healthy donor-derived Th1m and Th17m cells after IL-18 and IL-12 stimulation in vitro. Results Plasma IL-18 concentrations correlated to concentrations of Th1-associated proteins (IFN-γ, CXCL9, CXCL11, CXCL10, PDL1) in CD and UC. Interestingly, in UC patients, IL-18 concentrations also correlated to Th17-associated proteins (IL-12B, IL-17A, IL-24). In agreement, preliminary in vitro data showed that IL-18 + IL-12 stimulation increases IL-17A- and IFN-γ-secreting cell frequencies in CCR6+ Th17m cells. In CD, plasma IL-18 concentrations correlated to frequencies of circulating gut-homing CCR6+CXCR3+CCR4+ Th17m, a pathogenic population known to acquire Th1 features and IFN-γ production. Ileal and colonic mRNA expression of IL-18 pathway genes associated with degree of histological inflammation. Higher IL-18 plasma concentrations at diagnosis associated with moderate to severe disease and worse endoscopic scores in both CD and UC and greater disease extent in UC, suggesting a relationship between IL-18 and disease severity. In line with its preferential production in the ileum, plasma IL-18 concentrations were significantly higher in CD patients with ileal involvement compared to CD patients with colonic disease. Conclusion We identify IL-18 as a potential enhancer of both Th1-like and Th17-driven inflammation. High plasma IL-18 is detectable in subgroups of CD and UC patients, raising the question whether IL-18 acts on a specific disease-associated Thm cell population.

Indirect Markers of Intestinal Damage in IgA Nephropathy

Introduction: Presence of subclinical intestinal inflammation has repeatedly been shown in IgA nephropathy (IgAN) and the degree of histological inflammation has correlated with abnormal urinary findings. There is lack of noninvasive biomarkers evaluating the presence of subclinical intestinal damage in IgAN. We conducted this study hypothesizing that selected biomarkers regarded as indirect markers of intestinal damage could be elevated in IgAN. Methods: Eighty-five primary IgAN patients (median age 55 years, 54% men) participated in this single-center study in Tampere, Finland. None had end-stage kidney disease or previously diagnosed enteropathies. Celiac disease was excluded with serum transglutaminase 2 antibody (TG2Ab) and endomysial antibody tests and inflammatory bowel disease with fecal calprotectin. Intestinal damage was evaluated from sera with analyses of intestinal fatty-acid binding protein (I-FABP), soluble cluster of differentiation molecule 14 (sCD14), and lipopolysaccharide binding protein. Fourteen people suffering from dyspepsia and 15 healthy people served as controls. Results: I-FABP levels among IgAN patients were higher than in the healthy controls (median 830 pg/mL vs. 289 pg/mL, p < 0.001). Also, sCD14 was increased in IgAN patients compared to dyspepsia controls. Although TG2Ab levels were within the normal range among IgAN patients, they were higher than in the healthy controls (median 1.3 U/mL vs. 0.6 U/mL, p < 0.001). Conclusions: Elevated serum levels of I-FABP were present in primary IgAN patients without known enteropathies. Serum I-FABP may indicate the presence of subclinical intestinal damage. These findings encourage further investigation into the role of the intestine in the pathophysiology of IgAN.

Correlation of clinical and trichoscopy features with the degree of histologic inflammation in lichen planopilaris and frontal fibrosing alopecia in a cross-sectional study

Correlation of clinical and trichoscopy features with the degree of histologic inflammation in lichen planopilaris and frontal fibrosing alopecia in a cross-sectional study

The Management of Hepatitis B Flare in Pregnancy

Background: Hepatitis B infection during pregnancy is still a unique problem for the mother and her fetus. These include the effects of hepatitis B on maternal and fetal health, the effects of pregnancy on hepatitis B infection in pregnancy, treatment of hepatitis B during pregnancy and prevention of mother-to-child transmission. Case description: A young woman was referred for jaundice in pregnancy. Physical examination revealed icteric sclera in both eyes. Laboratory tests show increased liver function as well as bilirubin. for testing for hepatitis B reactive. The patient received lamivudine therapy and cesarean section therapy. Conclusion: Management and treatment of chronic hepatitis B is difficult because of the variable course of the disease. It is even more complex in pregnant patients. Joint decision-making between physicians and female patients regarding the timing of initiation of antiviral therapy is critical to improving outcomes. Optimal initiation of antiviral therapy in the general population depends on the histologic degree of inflammation and fibrosis. We now know that post-partum HBIG and vaccination for infants born to chronically infected mothers can be ineffective in preventing MTCT to regulate increased maternal HBV viremia.

The Medium-Chain Fatty Acid Receptor GPR84 Mediates Myeloid Cell Infiltration Promoting Steatohepatitis and Fibrosis.

Medium-chain fatty acids (MCFAs) have been associated with anti-steatotic effects in hepatocytes. Expression of the MCFA receptor GPR84 (G protein-coupled receptor 84) is induced in immune cells under inflammatory conditions and can promote fibrogenesis. We aimed at deciphering the role of GPR84 in the pathogenesis of non-alcoholic steatohepatitis (NASH), exploring its potential as a therapeutic target. GPR84 expression is upregulated in liver from patients with non-alcoholic fatty liver disease (NAFLD), correlating with the histological degree of inflammation and fibrosis. In mouse and human, activated monocytes and neutrophils upregulate GPR84 expression. Chemotaxis of these myeloid cells by GPR84 stimulation is inhibited by two novel, small molecule GPR84 antagonists. Upon acute liver injury in mice, treatment with GPR84 antagonists significantly reduced the hepatic recruitment of neutrophils, monocytes, and monocyte-derived macrophages (MoMF). We, therefore, evaluated the therapeutic inhibition of GPR84 by these two novel antagonists in comparison to selonsertib, an apoptosis signal-regulating kinase 1 (ASK1) inhibitor, in three NASH mouse models. Pharmacological inhibition of GPR84 significantly reduced macrophage accumulation and ameliorated inflammation and fibrosis, to an extent similar to selonsertib. In conclusion, our findings support that GPR84 mediates myeloid cell infiltration in liver injury and is a promising therapeutic target in steatohepatitis and fibrosis.

Use of Magnetic Resonance Index of Activity (MaRIA) in the Preoperative Assessment of Small Bowel Crohn’s Disease

IntroductionAccurate quantification of the inflammatory activity in Crohn’s Disease is essential to decide the adequate treatment for each patient. The aim of the present study is to assess the correlation between the pre-operative Magnetic Resonance Index of Activity (MaRIA) and the histologic degree of inflammation from surgically resected intestinal Crohn’s Disease lesions. MethodsThis is a prospective study including a consecutive case series of patients with small bowel Crohn’s Disease, who underwent surgical resection. A Magnetic Resonance Enterography was performed during the three months prior to surgery, applying a pre-established protocol. Relative contrast enhancements, wall thickness, presence of edema or ulcerations were the parameters used to calculate the MaRIA Index. All patients underwent surgery and every specimen was analysed. The modified Chiorean classification was applied for the histological analysis and an ordinal regression analysis was used in order to correlate MaRIA and the grade of inflammation for each lesion. Results59 lesions from 35 different patients were analysed. The degree of inflammation of the lesions was statistically correlated to the MaRIA values (P = .002). The MaRIA index was significantly different (P < .001) between the different histological type of the Crohn’s Disease lesions (inflammatory/ fibrotic). The best cut-off for detecting severe inflammation using MaRIA was 20 (AUC: 0.741, 74.1% sensitivity and 78.1% specificity). ConclusionMaRIA is a reliable tool to distinguish inflammatory from fibrotic lesions; therefore, it could be considered crucial to determine the most appropriate Crohn’s Disease treatment for each patient.

La resonancia magnética y el índice MaRIA en la valoración preoperatoria de la enfermedad de Crohn ileal

BackgroundAccurate quantification of the inflammatory activity in Crohn's Disease is essential to determine adequate treatment for each patient. The aim of the present study is to assess the correlation between the pre-operative Magnetic Resonance Index of Activity (MaRIA) and the histologic degree of inflammation from surgically resected intestinal Crohn's Disease lesions. MethodsThis is a prospective study including a consecutive case series of patients with small bowel Crohn's Disease, who underwent surgical resection. Magnetic resonance enterography was performed in the 3months prior to surgery, applying a pre-established protocol. Relative contrast enhancements, wall thickness, presence of edema or ulcerations were the parameters used to calculate the MaRIA Index. All patients underwent surgery and every specimen was analyzed. The modified Chiorean classification was applied for the histological analysis and an ordinal regression analysis was used to correlate MaRIA and the grade of inflammation for each lesion. Results59 lesions from 35 different patients were analyzed. The degree of inflammation of the lesions was statistically correlated to the MaRIA values (P=.002). The MaRIA index was significantly different (P<.001) between the different histological types of the Crohn's Disease lesions (inflammatory/ fibrotic). The best cut-off for detecting severe inflammation using MaRIA was 20 (AUC: 0.741; 74.1% sensitivity and 78.1% specificity). ConclusionMaRIA is a reliable tool to distinguish inflammatory from fibrotic lesions. Therefore, it could be considered essential for determining the most appropriate Crohn's Disease treatment for each patient.

Retrospective Study of the Significant Predictive Role of Inflammatory Degree in Initial and Repeat Prostate Biopsy Specimens for Detecting Prostate Cancer.

PurposeThe purpose of this study was to determine whether histologic inflammation (HI) in initial and repeat prostate biopsy specimens was significantly associated with the detection of prostate cancer.Materials and MethodsBetween 2005 and 2017, the clinicopathological records of patients with high prostatespecific antigen (PSA) levels who underwent initial and repeat prostate biopsies were retrospectively reviewed. The presence of HI and its degree in each biopsied specimen were interpreted by one uropathologist with 20 years of experience. The association between HI and cancer diagnosis was statistically assessed, with p < 0.05 considered significant, and the cancer and non-cancer groups were compared.ResultsAmong the 522 patients with a median PSA levels of 6.5 ng/dL, including 258 (49.4%) whose cancer was diagnosed following repeat biopsy, the median degrees of HI in the initial and repeat biopsies were 25.0% and 41.7%, respectively. Furthermore, 211 (40.4%) and 247 (47.3%) patients had HI (> 0%) on biopsied specimens, respectively. Comparison of the cancer and noncancer groups revealed that a greater rate of HI specimens in the initial biopsy was associated with fewer prostate cancer diagnoses following repeat biopsy (p < 0.001). Other comparisons between the cancer and non-cancer groups showed that the cancer group had a significantly higher rate of hypertension, whereas those non-cancer group had a significantly higher rate of benign prostatic hyperplasia and prostatitis (p < 0.05).ConclusionA finding of a lesser degree of HI in the initial and a greater degree of HI in the repeat biopsied specimens was associated with the higher probability of cancer diagnosis in patients with high PSA levels.

Correlation between fecal calprotectin and inflammation in the surgical specimen of Crohn's disease

BackgroundAn accurate assessment of the inflammatory activity is crucial to establish the most appropriate treatment in Crohn's disease (CD). The present study aimed to evaluate the utility of preoperative fecal calprotectin (FC) measurement in small bowel CD and its relationship with inflammatory activity in surgical pathology specimens. MethodsThis was a prospective observational study including all the patients with small bowel CD operated on at our center between March 2011 and September 2013. Preoperative laboratory and stool tests were performed. A meticulous exploration of entire small bowel was performed during surgery, and the resected bowel (or a sample of whole intestinal wall, if strictureplasty) was submitted for pathologic analyses. Chiorean's score was used to grade pathologic features (inflammation or fibrosis). In case of multiple lesions, the most inflammatory component was considered. ResultsThirty-eight consecutive patients were included in the study, and 81 small bowel lesions were identified. Among inflammatory markers, only FC was significantly associated with the degree of histologic inflammation in the surgical specimen (P < 0.003). FC reflected histologic inflammatory activity with an area under the receiver-operating characteristic curve of 0.85 (CI: 0.70-0.99; P < 0.001). A cutoff value of 170 μg/g had 81% sensitivity and 85% specificity for diagnosis of moderate or severe inflammation. Ordinal regression analysis showed the probability of a greater or lesser degree of inflammation based on the value of preoperative FC. ConclusionsFC is an excellent biomarker of inflammatory activity in small bowel CD as it correlates with histologic inflammation in the surgical specimen.

Letter: mucosal healing is associated with improved long‐term outcomes in Crohn's disease

We read with interest the article by Shah et al. comparing long-term outcomes in patients with active Crohn's disease who achieve mucosal healing compared with those who do not.1 The authors found that achieving mucosal healing at first endoscopic assessment is associated with increased rates of long-term clinical remission and maintenance of mucosal healing in active Crohn's disease, and may therefore be a reasonable therapeutic target. Shah et al.'s meta-analysis gives rise to the question as to whether either mucosal healing or clinical remission should be the main treatment goal in Crohn's disease. Precise definitions of mucosal healing in Crohn's disease need to be resolved and proper comparative effectiveness trials need to be performed to confirm that this endpoint is clinically meaningful. In some studies, mucosal healing was defined as a Mayo Score of 0 or 1.2, 3 A score of ‘1’ (erythema, diminished vascular markings) might plausibly describe patients with a broad spectrum of symptoms. Therefore, despite meeting the study's definition of mucosal healing, there remains a significant proportion of patients with some degree of persistent endoscopic inflammation. To add to the confusion, the authors could not conclude this result, because it used an entirely different definition of mucosal healing. At the same time, mucosal healing has been refined to a microscopic level, with some studies showing a significant association between the degree of histological inflammation and an increased risk of flaring over the course of Crohn's disease. We agree that mucosal healing is an important endpoint that should be studied in clinical trials. However, some issues still limit the use of mucosal healing as a therapeutic target of Crohn's disease in clinical practice. Firstly, a validated standard system for grading histologic activity does not exist. Validation is a prerequisite to standardize reporting and grading. Secondly, the exact definition of histologic healing, as well as their impact on clinical outcome of Crohn's disease, has yet to be clarified. Thirdly, the optimal staining method for grading the severity of inflammation is still unclear. Haematoxylin–eosin is the most frequently used staining, but more expensive methods, such as immunohistochemistry, may provide information. Fourth, the timing and site of the biopsy to show normalized histology have to be clarified. Fifth, mucosal healing is not a reliable target in clinical practice – it is not an easy goal to reach, and inflammation may persist despite clinical–endoscopic remission. Our study reported that mucosal healing did not predict sustained clinical remission in patients with inflammatory bowel disease when infliximab therapies had been stopped.4 In summary, before considering mucosal healing as a reliable target for the treatment of Crohn's disease, large prospective studies will have to address the key issues we have discussed. Declaration of personal and funding interests: None.

Gene Expression in Biopsies of Acute Rejection and Interstitial Fibrosis/Tubular Atrophy Reveals Highly Shared Mechanisms That Correlate With Worse Long-Term Outcomes.

Interstitial fibrosis and tubular atrophy (IFTA) is found in approximately 25% of 1-year biopsies posttransplant. It is known that IFTA correlates with decreased graft survival when histological evidence of inflammation is present. Identifying the mechanistic etiology of IFTA is important to understanding why long-term graft survival has not changed as expected despite improved immunosuppression and dramatically reduced rates of clinical acute rejection (AR) (Services UDoHaH. http://www.ustransplant.org/annual_reports/current/509a_ki.htm). Gene expression profiles of 234 graft biopsy samples were obtained with matching clinical and outcome data. Eighty-one IFTA biopsies were divided into subphenotypes by degree of histological inflammation: IFTA with AR, IFTA with inflammation, and IFTA without inflammation. Samples with AR (n=54) and normally functioning transplants (TX; n=99) were used in comparisons. A novel analysis using gene coexpression networks revealed that all IFTA phenotypes were strongly enriched for dysregulated gene pathways and these were shared with the biopsy profiles of AR, including IFTA samples without histological evidence of inflammation. Thus, by molecular profiling we demonstrate that most IFTA samples have ongoing immune-mediated injury or chronic rejection that is more sensitively detected by gene expression profiling. These molecular biopsy profiles correlated with future graft loss in IFTA samples without inflammation.

Disaccharidase activity in children undergoing esophagogastroduodenoscopy: A systematic review.

To investigate the utility of intestinal disaccharide analysis during esophagogastroduodenoscopy (EGD) in children, we performed a systematic review of studies examining disaccharide activity. All full-length articles published in English during 1966-2014 were included if: (1) participants had small intestinal biopsy evaluation of disaccharide activity; (2) levels of lactase, sucrase, maltase or palatinase were reported; and (3) age of participants was under 18 years. Thirty articles examining 34753 disaccharide assays fulfilled the specific search, inclusion, and exclusion criteria. All of the studies were observational in design and 57% (17) were prospective. Sixteen studies were conducted in the United States and 9 European studies were identified. The biggest study enrolled about 30, 314 procedures and 13 studies investigated fewer than 50 procedures. Eleven studies examined Caucasian subjects, 3 studies examined Asian subjects, and 6 examined African subjects. Only one Hispanic subject was included. In studies reporting disaccharide deficiency, the overall proportion of lactase deficiency was 39.2%, sucrase deficiency was 9.0%, maltase deficiency was 12.6% and palatinase deficiency was 9.1%. The prevalence of duodenal inflammatory changes ranged from 6% to 24% for non-specific histological lesions (e.g., duodenitis). Sixteen studies examined the association of histologic findings with disaccharide activities, and 12 studies reported an inverse association between degree of histologic inflammation and disaccharide levels. We reviewed 30 studies including 34753 biopsy specimens with disaccharide analysis from children undergoing EGD. Our findings advocate a large study is to further illuminate the importance of EGD with disaccharide analysis in children.

Role of Prostatic Inflammation in the Clinical Presentation of Benign Prostatic Hyperplasia

ContextAlthough it was hypothesised >20 yr ago that prostatic inflammation could influence clinical presentation and possibly surgical outcome in patients with benign prostatic hyperplasia (BPH)-related lower urinary tract symptoms (LUTS), only more recently has compelling substantiating evidence become available. ObjectiveTo review the evidence for the role of inflammation in the clinical presentation and treatment of BPH/LUTS. Evidence acquisitionThis article is based primarily on material presented at a satellite symposium entitled, “Inflammation and Prostatic Diseases: From Bench to Bedside,” held during the 2015 annual meeting of the European Association of Urology in Madrid, Spain. Current data regarding the link between inflammation and BPH were reviewed. Evidence synthesisStudies such as the large-scale Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial and others have clearly demonstrated the association between the presence and/or degree of histologic inflammation and its impact on parameters such as prostate volume, voiding LUTS, and type of surgery required to treat BPH. Prostatic inflammation has been shown to increase by threefold the risk for acute urinary retention, an end point in the natural progression of BPH. Inflammation has been proposed as the common thread between the metabolic syndrome and BPH/LUTS, which frequently co-exist, and offers new therapeutic targets for medical treatment. Motivated patients can undertake lifestyle modifications (eg, weight, diet, exercise) to potentially prevent the need for surgery. Selective cyclooxygenase-2 inhibition appears promising as a therapeutic approach for inflammation, but its suitability for long-term use in the BPH population is limited by safety concerns. ConclusionsGreater understanding of the relationship between inflammation and the clinical presentation of BPH/LUTS provides an opportunity to effect clinical changes to improve treatment outcomes. Patient summaryAn increased understanding of the role of prostatic inflammation in the pathogenesis, symptomatology, and progression of benign prostatic hyperplasia (BPH) is likely to change the treatment paradigm for BPH.

Tu1522 Implementing Chromoendoscopy for Surveillance in Inflammatory Bowel Disease Does Not Increase Dysplasia Detection Compared to Conventional Colonoscopy With Random Biopsies: a Retrospective Study

Tu1522 Implementing Chromoendoscopy for Surveillance in Inflammatory Bowel Disease Does Not Increase Dysplasia Detection Compared to Conventional Colonoscopy With Random Biopsies: a Retrospective Study

Ozone therapy as an adjunct to vancomycin enhances bacterial elimination in methicillin resistant Staphylococcus aureus mediastinitis

BackgroundWe aimed to investigate the influence of intraperitoneal ozone therapy on bacterial elimination and mediastinal inflammation in experimental Staphylococcus aureus mediastinitis. Materials and methodsForty Wistar-Albino rats were randomized into five groups (eight per group) as follows: uncontaminated group, untreated contaminated group, ozone group, vancomycin group, and vancomycin + ozone group. Uncontaminated group underwent upper median sternotomy. The remaining four groups were inoculated with 0.5 mL 108 colony-forming units/mL methicillin-resistant Staphylococcus aureus in the mediastinal and sternal layers. Untreated contaminated group had no treatment. Rats in the vancomycin group received intramuscular vancomycin (40 mg/kg/d), and ozone was administered intraperitoneally (70 μg/mL, 1 mg/kg/d) in the ozone group for the treatment of mediastinitis. Vancomycin + ozone group rats were treated by the combination of both methods. At the end of 10 d, quantitative bacterial cultures and sternal tissue samples were obtained for determination of bacterial counts and histologic degree of inflammation. ResultsBoth the vancomycin and the ozone treatments caused significant reduction of bacterial counts in quantitative bacterial cultures. Combination of vancomycin and ozone treatments resulted in further reduction of bacterial counts in mediastinum and sternum. Histologic examination of tissue samples revealed significant reduction in severity of mediastinitis related inflammation in vancomycin and vancomycin + ozone groups compared with untreated contaminated group. ConclusionsOzone therapy as an adjunct to vancomycin leads to enhanced bacterial elimination in infected sternal and mediastinal tissues in experimental methicillin-resistant Staphylococcus aureus mediastinitis. The benefit of adjuvant ozone therapy is suggested to be related to its bactericidal effect.

Liver FOXP3 and PD1/PDL1 Expression is Down-Regulated in Chronic HBV Hepatitis on Maintained Remission Related to the Degree of Inflammation

Background and Aim: T cell expression of PD1 and inhibition of T effector cells by Foxp3+-T regulatory cells are among the most powerful mechanisms for achieving a balanced immune response. Our aim was to investigate, how liver FOXP3 and PD1/PDL1 expression is regulated in chronic HBV hepatitis (CHB) on maintained long-term remission in comparison with active disease, and whether they are correlated to the expression of pro- and anti-inflammatory cytokines and apoptosis mediators, along with the degree of histological inflammation and markers of T cell effector restoration.Methods: Fifty-three HBeAg-negative CHB patients with both active (30) and completely remitted disease on long-term antiviral treatment (23) and four controls (submitted to liver biopsy due to a mild increase of aminotransferases but without liver necroinflammatory and architecture changes) were enrolled in the study. Liver mRNA levels of immunoregulatory genes (FOXP3, IL10, TGFB1, and those of PD1/PDL1/PDL2 pathway), major apoptosis mediators (FAS, FASL, TNFA, TRAIL), cytokines of effector T cell restoration (IL2, IFNG), and those of IL1B, CD4, and CD8, were evaluated by quantitative real-time reverse-transcriptase PCR and were correlated with each other, along with the intensity of liver inflammation and fibrosis staging. The expression and localization of FOXP3, PD1, PDL1, CD4, and CD8 were also assessed by immunohistochemistry.Results: The expression of FOXP3, IL10, TGFB1, PD1, PDL1, FASL, and CD8 was significantly down-regulated in the remission state. In contrast, liver expression of IL2 and IFNG, along with CD4, IL1B, TNFA, and FAS did not change significantly. Moreover, FOXP3, PD1, PDL1, and CD8 transcripts were positively correlated to the intensity of liver inflammation.Conclusion: Our data indicate that in the CHB disease model, the immunosuppressive liver environment is down-regulated in the maintained on-treatment long-term remission state and correlates with the intensity of liver inflammation, but not liver T cell restoration.

Treatment of Inflammatory Bowel Disease With Genetically Engineered Bacteria

Treatment of Inflammatory Bowel Disease With Genetically Engineered Bacteria

M1256 The Relationship Between Abdominal Fat Amount and the Diverticular Disease

Aim. The aim of this study was to assess the role of fecal calprotectin (FC) in diagnosis of complicated colonic diverticular disease (DD) and to compare it with uncomplicated colonic DD and matched controls. Methods. We studied 57 consecutive patients with a new endoscopic diagnosis of colonic diverticulosis (45 with asymptomatic uncomplicated DD, and 12 with acute diverticulitis) and 25 healthy controls. The level of FC was measured in every case by a semiquantitative test with three categories of results: type 1 (under 15 μg/g), type 2 (15-60 μg/g), and type 3 (more than 60 μg/g). The results were correlated with the degree of histological inflammation of colonic mucosa that was assessed by the degree of lymphocytic cell density. Results. We found higher FC values in acute uncomplicated diverticulitis (p<0.05) than in asymptomatic uncomplicated DD and in healthy controls. There were no differences between uncomplicated colonic DD and healthy controls. FC values increase according to the increase of lymphocytic cell density, showing a statistically significant correlation (p<0. 05). Patients with acute diverticulitis were treated with antibiotics for 10 days; in these patients, reassessment of FC after three months revealed a significant decrease comparingwith the initial level. Conclusions. FCmay be useful to detect colonic inflammation in DD and in distinguishing acute diverticulitis from uncomplicated colonic DD and healthy controls. Also, FC may be useful for follow-up after treatment.

Leukocytes, C-Reactive Protein and Interleukin-6 in Acute Appendicitis in Children: Diagnostic Value and Association with Histological Findings

Background: Many efforts have been made to find diagnostic tools that would help select children with clinical signs of acute appendicitis that would need immediate appendectomy and to find tools that would reduce the numbers of negative appendectomies. Aim: We aimed to show the association between leukocyte count, level of C-reactive protein and interleukin-6 in peripheral blood on the one side and the degree of histological findings on appendix after appendectomy on the other side in children with high clinical probability for appendicitis (Alvarado score>7). Methods: We analyzed 80 patients of both genders, younger than 15 years, with Alvarado score>7, which underwent open appendectomy with subsequent histological analysis of removed appendices. We sampled 20 consecutive cases without signs of inflammation (group I), 20 cases with pathological signs of incipient inflammation (group II), 20 cases with signs of phlegmonous inflammation (group III) and 20 cases with signs of perforated appendix (group IV). Prior to appendectomy, a peripheral blood was sampled and sent for analysis of leukocyte count and C-reactive protein and interleukine-6 level. We compared values of all 3 measured parameters according to histological findings; we also used Receiver Operating Characteristics (ROC) analysis in order to evaluate diagnostic thresholds for detecting the histological signs of appendicitis. Results: The lowest values of all observed parameters were found in group of negative appendicitis while highest were observed in the group of perforated appendicitis. We have observed a significant between group differences in values of all three parameters according to the degree of histological inflammation (p<0.001). ROC analysis demonstrated that interleukine-6 had the best diagnostic performance in detecting patients with histological signs of appendicitis (AUROC=0.99; 95% CI=0.99-1.00) when compared to CRP and leukocyte count (p<0.05). There was no significant difference in diagnostic performance between CRP and leukocytes counts (p=0.35). Conclusion: Leukocyte count, CRP and interleukine-6 are very useful markers which may help in diagnostics and differentiation of phlegmonous and perforated appendicitis. In patients with high probability of appendicitis, measurement of interleukine-6 may help in better patient selection.

Recombinant human erythropoietin reduces epithelial cell apoptosis and attenuates bleomycin‐induced pneumonitis in mice

Erythropoietin (EPO) has recently been demonstrated to have a tissue protective role by acting as an anti-apoptotic agent in various tissues, such as brain, spinal cord, heart and kidney. The purpose of this study was to determine whether human recombinant EPO reduces epithelial cell apoptosis and attenuates bleomycin-induced pneumonitis in mice. Bleomycin was instilled intratracheally into C57BL/6 mice. Recombinant human EPO or saline was injected intraperitoneally, daily from day 5 to day 13 after bleomycin instillation. EPO receptor was expressed in bronchiolar and alveolar type II cells. At 14 days after instillation, the number of terminal uridine deoxynucleotidyl transferase nick end-labelled positive cells in the lung was decreased, and the histological degree of inflammation and fibrosis was attenuated in mice injected with EPO compared with controls. Expression of phosphorylated Akt and Erk, which are thought to mediate the survival signalling pathway induced by EPO, tended to be increased in lung tissues from mice treated with EPO compared with those from mice treated with saline after bleomycin instillation. As it is likely that EPO protects epithelial cells from injury and apoptosis, EPO administration could be a potential therapeutic strategy for the prevention of lung injury.