scholarly journals Correlation of Paraoxonase-1 with the Severity of Crohn’s Disease

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2603
Author(s):  
Katarzyna Szczeklik ◽  
Tomasz Mach ◽  
Dorota Cibor ◽  
Danuta Owczarek ◽  
Jacek Sapa ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Sensitivity And Specificity ◽  
Activity Index ◽  
Area Under The Curve ◽  
Density Lipoprotein ◽  
High Sensitivity ◽  
Paraoxonase 1 ◽  
Control Group ◽  
Operating Characteristics

Diagnostics of Crohn’s disease (CD) requires noninvasive biomarkers facilitating early detection and differentiation of the disease. Therefore, in this study, we aimed to determine the relationship between paraoxonase-1 (PON-1), the severity of CD, oxidative stress, and inflammation in CD. The CD activity index was based on the current classification. Plasma PON-1 was measured in 47 patients with CD, and in 23 control volunteers. Using quantitative variables such as receiver operating characteristics (ROC) (area under the curve (AUC)), the diagnostic utility of PON-1 in differentiating the severity of CD was assessed. Circulating PON-1 was found to be decreased in the CD group compared to the control group (269.89 vs. 402.56 U/L, respectively), and it correlated well with the disease activity. PON-1 correlated positively with hemoglobin (Hb) (r = 0.539, p < 0.001), hematocrit (Ht) (r = 0.48, p < 0.001), total cholesterol (TC) (r = 0.343, p < 0.001), high density lipoprotein (HDL) (r = 0.536, p < 0.001), low density lipoprotein (LDL) (r = 0.54, p < 0.001), and triglyceride (TG) (r = 0.561, p < 0.001) and correlated negatively with white blood cell count (WBC) (r = −0.262, p = 0.029), platelet count (PLT) (r = −0.326, p = 0.006), C-reactive protein (CRP) (r = −0.61, p < 0.001), and malondialdehyde (MDA) (r = −0.924, p < 0.001). PON-1 as a marker for CD differentiation possessed a sensitivity and specificity of 93.62% and 91.30%, respectively. CD was found to be associated with the decrease in the levels of PON-1, which correlates well with activity of the disease and reflects the intensification of inflammation, as well as intensified lipid peroxidation. High sensitivity and specificity of PON-1 determines its selection as a good screening test for CD severity.

scholarly journals Oral 5-Aminosalicyclic Acid Versus 6-Methylprednisolone in Active Crohn's Disease

1990 ◽  
Vol 4 (7) ◽  
pp. 446-451 ◽  
Author(s):  
Jürgen Schölmerich ◽  
Harro Jenss ◽  
Franz Hartmann ◽  
Hanne Döpfer ◽  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Activity Index ◽  
Area Under The Curve ◽  
Disease Activity Index ◽  
Entrance Examination ◽  
Aminosalicylic Acid ◽  
Double Blind ◽  
Treatment Groups ◽  
Starting Dose

The response to 5-aminosalicylic acid (5-ASA) in active Crohn's disease was studied in comparison to methylprednisolone in a 24 week randomized double-blind multicentre study. Sixty-two patients were included in the analysis. Thirty were treated with 500 mg 5-ASA qid and 32 with methylprednisolone (starting dose 48 mg for one week, then reduced weekly to 32, 24, 20, 16 and 12 mg with maintenance at 8 mg/day for the remaining 18 weeks). Mean age, earlier surgical intervention, localization of Crohn's disease and extraintestinal manifestations were not different in both groups. The Crohn's disease activity index (CDAI) and the van Hees index were not significantly different in both treatment groups at the entrance examination (median CDAI 232 in the 5-ASA group and 220 in the methylprednisolone group). According to the protocol, treatment was stopped due to insufficient efficacy in 73% of the patients receiving 5-ASA and in 34% of the patients receiving methylprednisolone (x2test P=0.0019). The area under the curve for the CDAl was significantly greater in 5-ASA (median 170) than in methylprednisolone (P≤0.007) (68). Eleven per cent of patients taking 5-ASA and 26% of patients taking methylprednisolone presented relevant side effects to treatment (not significant). It is concluded from these data that 5-ASA at the dose used in this study is not efficient in the treatment of active Crohn's disease. Considering recent studies in ulcerative colitis, a trial using a higher dose is indicated.

scholarly journals Serum Syndecan-1 Levels and Its Relationship to Disease Activity in Patients with Crohn’s Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Cem Çekiç ◽  
Adnan Kırcı ◽  
Sezgin Vatansever ◽  
Fatih Aslan ◽  
Huriye Erbak Yılmaz ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Activity Index ◽  
Normal Population ◽  
Disease Activity Index ◽  
Serum Levels ◽  
Control Group ◽  
Serum Samples ◽  
Reactive Protein

Background. Syndecan-1 (SDC-1), a member of the family of heparan sulfate proteoglycans, plays an important role in the resolution of inflammation. This study aimed to investigate the relationship between SDC-1 and disease activity in Crohn’s disease (CD).Methods. Serum samples of 54 patients with CD and 30 healthy controls were obtained. First, SDC-1 levels of the CD patients were compared to the control group. Subsequently, SDC-1 levels were analyzed in patients with CD in active and remission periods. Finally, SDC-1 efficacy in predicting disease activity was evaluated by performing correlation analysis between SDC-1 and C-reactive protein (CRP) and Crohn’s disease activity index (CDAI).Results. SDC-1 level was higher in the CD group (61.9 ± 42.6 ng/mL) compared with the control group (34.1 ± 8.0 ng/mL)p=0.03. SDC-1 levels were higher in active CD patients (97.1 ± 40.3 ng/mL) compared with those in remission (33.7 ± 13.5 ng/mL)p<0.001. A significant positive correlation was found between SDC-1 and CRP (r=0.687,p<0.001) and between SDC-1 and CDAI (r=0.747,p<0.001).Conclusion. Serum levels of SDC-1 are higher in CD compared to the normal population and can be an effective marker of disease severity.

scholarly journals The Association Between Genetic Variants, Pharmacokinetics, and Infliximab Efficacy in Pediatric Patients With Crohn's Disease in China

2021 ◽  
Vol 9 ◽  
Author(s):  
Wenhui Hu ◽  
Yan Feng ◽  
Ziqing Ye ◽  
Zifei Tang ◽  
Lai Qian ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Genetic Variants ◽  
Pediatric Patients ◽  
Activity Index ◽  
Area Under The Curve ◽  
Disease Activity Index ◽  
Threshold Level ◽  
Mucosal Healing ◽  
Nucleotide Polymorphisms

Background: Infliximab is an effective therapy for Crohn's disease (CD). Early non-invasive predictors of disease remission allow for modification of treatments. The aim of this study was to investigate the associations between genetic variants, pharmacokinetics, and infliximab efficacy in pediatric patients with CD.Methods: This retrospective observational study included CD patients under infliximab therapy between August 2015 and December 2020. Information on demographics, laboratory tests, medication data, and disease activity index was collected. The trough levels of infliximab (TLI) and antibodies to infliximab (ATI) were measured at week 14, and reactive drug monitoring was performed during follow-up. Ten single-nucleotide polymorphisms involved in the NF-κB-mediated inflammatory response, pharmacokinetics, and therapeutic response to infliximab were genotyped.Results: A total of 62 pediatric CD patients were enrolled. The clinical remission (CR) rate was 69.4 and 63.2% at week 14 and week 30, respectively. TLI at week 14 was significantly independently associated with CR at week 14 and mucosal healing (MH) at week 30 (p = 0.007 and p = 0.025, respectively). The optimal TLI threshold level capable of distinguishing between the CR and non-CR groups was 2.62 μg/ml (p &lt; 0.001, area under the curve = 0.79, sensitivity = 69.2%, specificity = 78.9%), while that capable of distinguishing between the MH and non-MH groups was 3.34 μg/ml (p &lt; 0.001, area under the curve = 0.85, sensitivity = 78.6%, specificity = 79.4%). Rs3397 in TNFRSF1B was associated with time to ATI production in CD patients (p &lt; 0.001).Conclusions: Higher TLI contributed to achieving MH. Genotyping rs3397 in TNFRSF1B may identify patients who are prone to generating immunogenicity to drugs.

scholarly journals Significance of ultrasonography of the terminal ileum in moderate Crohn's disease

2006 ◽  
Vol 63 (9) ◽  
pp. 787-792 ◽  
Author(s):  
Leposava Lukic-Kostic ◽  
Jasna Jovic ◽  
Slobodan Sekulovic
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Lymph Nodes ◽  
Terminal Ileum ◽  
Clinical Laboratory ◽  
Activity Index ◽  
Disease Activity Index ◽  
Unknown Etiology ◽  
Control Group ◽  
Ultrasonographic Examination

Background/aim: Crohn's disease (CD) is a chronic granulomatous inflammatory disease of unknown etiology, involving any part of the gastrointestinal tract, and frequently followed by extra intestinal manifestations. The use of ultrasonography plays a significant role in diagnosing this disease, as well as in monitoring the effects of the therapy. The aim of this study was to assess the use of ultrasonographic diagnostics in the patients with moderate serious and the mild form of CD. Methods. The study involved 30 patients both sexes with CD of moderate form determined using the standard diagnostics, according to the Crohn's Disease Activity Index - CDAI ranging from 220?400. The patients were divided into two groups with CDAI > 320 (Ia), and CDAI between 220 and 320 (Ib), respectively. The Control group was made of 19 patients with the mildly active stage of the disease and the CDAI values in the range from 100?220. The patients were submitted to an ultrasonographic examination of the terminal ileum affected with CD in order to determine the length of the affected segment of intestine, the thickness of the wall, the changes of the structure of the wall, the changes of the surrounding mesenterium with the enlarged lymph nodes. CD complications, abscesses, and enteroenteral fistulas were investigated, too. Results. The comparison of the ultrasonographic findings of the three groups revealed that more serious clinical laboratory image of CD significantly correlated with the higher length of the affected segment (p < 0.001), higher thickness of the wall (p < 0.001), the higher number and the larger lymph nodes of the mesenterium (p < 0.001). Only the most serious patients were found to have abscess of the ileocecal area (Ia ? 40%). There was no difference found between the groups regarding the occurrence of enteroenteral fistulas. Conclusion. Considering the obtained results and data from the literature, it could be concluded that an ultrasonographic examination of the ileocecal area plays an important role in the diagnostic procedure in the management of a patient with CD. Of particular significance is the possibility to use this examination in monitoring the effects of the therapy in patients with CD.

scholarly journals Peripheral Blood Inflammatory Markers and Crohn’s Disease: Lymphocytes Counts Could Predict Stricture Lesions 

2020 ◽  
Author(s):  
Juanjuan Zhang ◽  
Zhen Guo ◽  
Yanqing Diao ◽  
Binlin Da ◽  
Zhiming Wang ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Peripheral Blood ◽  
Inflammatory Markers ◽  
Activity Index ◽  
Area Under The Curve ◽  
Full Blood Count ◽  
Intestinal Fibrosis ◽  
Jinling Hospital ◽  
Single Balloon

Abstract Background: Intestinal stricture is a complication of Crohn’s disease (CD) due to fibrosis, but there are no biomarkers for predicting intestinal strictures before clinical obstruction. It is reported that several types of lymphocytes (LC) are involved in the pathogenesis of intestinal fibrosis. However, few studies have focused on the peripheral blood LC in patients with CD associated stricture.Aim：To analyze the relationships between peripheral blood inflammatory markers especially LC and CD to provide evidence for CD diagnosis and therapy. Methods: A total of 158 CD patients who underwent single-balloon enteroscopy from January 2016 to June 2019 in Jinling Hospital were retrospectively enrolled. The Montreal classification, maintenance medicines, CD activity index (CDAI), simple endoscopic score for CD (SES-CD), full blood count and C-reactive protein (CRP) level were recorded. The relationships among peripheral blood inflammatory markers, disease activity and intestinal strictures were analyzed using SPSS 22.0. Results: After excluding 8 patients treated with azathioprine, which severely affects blood counts, 150 patients were divided into two groups: a stricture group (n=82) and non-stricture group (n=68). LC and the proportion of lymphocytes (LC%) were significantly lower in the stricture group than in the non-stricture group, p was 0.000 and 0.018, respectively, and LC was an independent risk factor of stricture lesion. In the subgroup analysis, 30 strictures without obstruction were classified as mild strictures, and 52 cases of obstruction were in the severe stricture group. LC notably decreased following stricture aggravation, p=0.000. The area under the curve (AUC) of LC predicting strictures was 0.711 with sensitivity of 73.5% and a specificity of 63.4% (cutoff: 1.245). Conclusion: LC gradually decreases as intestinal strictures aggravated and could be a new marker for predicting intestinal strictures in CD patients.

Association of Early Postinduction Adalimumab Exposure With Subsequent Clinical and Biomarker Remission in Children with Crohn’s Disease

2020 ◽  
Author(s):  
Firas Rinawi ◽  
Amanda Ricciuto ◽  
Peter C Church ◽  
Karen Frost ◽  
Eileen Crowley ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Primary Outcome ◽  
Activity Index ◽  
Area Under The Curve ◽  
Positive Likelihood Ratio ◽  
Fecal Calprotectin ◽  
Clinical Biomarker ◽  
Objective Outcomes ◽  
Trough Levels

Abstract Background Data on the association between early postinduction serum adalimumab (ADA) trough levels (TLs) and objective outcomes are scarce. The aim of this study was to investigate whether early ADA TLs at weeks 4 and 8 are associated with clinical and biomarker remission at week 24 in pediatric Crohn’s disease (CD). Methods Adalimumab TLs at weeks 4 and 8 were prospectively measured in anti-TNF-naïve children initiating treatment with ADA monotherapy for luminal inflammatory CD. The primary outcome was combined clinical and biomarker remission at week 24, defined as achieving steroid-free clinical remission (Pediatric CD activity index &lt;10) and biomarker remission (fecal calprotectin &lt;250 µg/g and CRP &lt;5 µg/mL). Results Among 65 patients, 39 (60%) achieved combined clinical/biomarker remission at week 24 without dose escalation. Adalimumab TLs at both weeks 4 and 8 were significantly higher in remitters vs nonremitters at week 24 (P &lt; 0.001 and P = 0.002, respectively). Adalimumab levels at weeks 4 and 8 were good predictors of combined clinical/biomarker remission at week 24 (area under the curve, 0.887, 95% CI, 0.798–0.942; and area under the curve, 0.761, 95% CI, 0.632–0.899, respectively). The best ADA TL cutoffs at weeks 4 and 8 for predicting clinical/biomarker remission at week 24 were 22.5 µg/mL (80% sensitivity, 90% specificity, positive likelihood ratio [LR+] 8.0, negative LR [LR-] 0.2) and 12.5 µg/mL (94% sensitivity, 60% specificity, LR+ 2.4, LR- 0.1), respectively. Higher induction doses per m2 correlated positively with TLs at weeks 4 and 8. Conclusion Greater early ADA exposure is associated with superior clinical/biomarker outcomes at week 24.

scholarly journals Efficacy and safety of adalimumab in Chinese patients with moderately to severely active Crohn’s disease: results from a randomized trial

2020 ◽  
Vol 13 ◽  
pp. 175628482093896
Author(s):  
Baili Chen ◽  
Xiang Gao ◽  
Jie Zhong ◽  
Jianlin Ren ◽  
Xuan Zhu ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Remission ◽  
Activity Index ◽  
High Sensitivity ◽  
Phase Iii ◽  
Chinese Patients ◽  
Efficacy And Safety ◽  
Open Label ◽  
Double Blind

Background and Aims: Efficacy of adalimumab in Crohn’s disease (CD) has not been shown in China. The aim of this study was to evaluate the efficacy and safety of adalimumab in Chinese patients with CD. Methods: This 26-week, multicenter, phase III study evaluated patients with moderately to severely active CD and elevated high-sensitivity C-reactive protein (⩾3 mg/l) who were naïve to anti–tumor necrosis factor therapy. Patients were randomized to double-blind adalimumab 160/80 mg at weeks 0/2 and 40 mg at weeks 4/6 or placebo at weeks 0/2 followed by blinded adalimumab 160/80 mg at weeks 4/6. At week 8, all patients received open-label 40 mg adalimumab every other week through week 26. The primary endpoint was clinical remission [CD activity index (CDAI) <150] at week 4. Clinical remission at week 26 was assessed in week-8 responders (decrease in CDAI ⩾70 points at week 8 from baseline) and compared with a clinically meaningful threshold of 30%. Adverse events (AEs) were recorded throughout the study. Results: At baseline, 205 patients were enrolled, with mean [standard deviation (SD)] age of 32.9 (9.9) years and CD duration of 2.7 (3.0) years. At week 4, 38/102 patients (37%) receiving adalimumab and 7/103 (7%) receiving placebo ( p < 0.001) achieved clinical remission. Among week-8 responders, 93/144 (65%) achieved clinical remission at week 26 ( p < 0.001). No unexpected AEs and no malignancies, active tuberculosis, or deaths were reported. Conclusions: Adalimumab induced and maintained remission in Chinese patients with CD. Safety results were consistent with the known safety profile of adalimumab. identifier: NCT02499783

scholarly journals Identification of potential metabolic biomarkers of rectal cancer and of the effect of neoadjuvant radiochemotherapy

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250453
Author(s):  
Elisabet Rodríguez-Tomàs ◽  
Meritxell Arenas ◽  
Junior Gómez ◽  
Johana Acosta ◽  
Jordi Trilla ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Area Under The Curve ◽  
Complete Response ◽  
Paraoxonase 1 ◽  
Control Group ◽  
Neoadjuvant Radiochemotherapy ◽  
Operating Characteristics ◽  
Number Of Patients ◽  
Circulating Levels

We report a pilot study on the feasibility of determinations of circulating levels of paraoxonase-1 (PON1) and compounds related to energy metabolism as biomarkers for the evaluation of patients with rectal cancer (RC), and the effects produced by neoadjuvant radiochemotherapy (NRCT). We studied 32 patients treated with radiotherapy plus capecitabine concomitant chemotherapy and 48 control subjects. We identified pre-NRCT PON1 and α-ketoglutarate as the parameters that best discriminated between RC patients and the control group. Receiver operating characteristics analysis of the combination of the two parameters showed an area under the curve (AUC) of 0.918. Moreover, patients who presented a pathological complete response (pCR) to treatment had lower plasma pre-NRCT valine concentrations (AUC of 0.826). Patients who had a relapse had lower concentrations of succinate (AUC of 0.833). The results of the present study illustrate the usefulness of investigating alterations in oxidative stress and metabolism in RC. Due to the small number of patients studied, our results must be considered preliminary, but they suggest that the determination of circulating levels of PON1 and α-ketoglutarate might be a valuable tool for the early diagnosis of RC, while the determination of valine and succinate might effectively predict pCR and the appearance of relapse.

scholarly journals The Crohn’s Disease and Proinflammatory Cytokines

2021 ◽  
Author(s):  
Ahmed Al Qteishat ◽  
Kiril Kirov ◽  
Dmitry O. Bokov
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Proinflammatory Cytokines ◽  
Activity Index ◽  
Systemic Reaction ◽  
The Body ◽  
Healthy People ◽  
Control Group ◽  
Tnf Α ◽  
Ifn Γ

Abstract The aim of the study was to examine the profile of the main proinflammatory cytokines in the serum of patients with Crohn's disease and establish their association with the severity and activity of the disease. A total of 61 patients (29 women (47.5%), 32 men (52.5%) aged from 18 to 40 years (mean age (30.42 ± 2.51) years) with the verified diagnosis of Crohn's disease in the active phase were examined. The control group consisted of 30 virtually healthy people (VHP) of corresponding age. Crohn's disease is characterized by reliable (p<0.05) increase of pro-inflammatory cytokines in blood compared to virtually healthy people: TNF-α – by 4.45 times (p<0.05), IL-1α – by 5.08 times (p<0.05), IL-6 – by 2.16 times (p<0.05), IL-8 – by 2.04 times (p<0.05), and IFN-γ – by 5.30 times (p<0.05), which can be due to the development of the active inflammatory process in the intestine and the systemic reaction of the body. The degree of increase in TNF-α and IFN-γ content, as well as the presence of direct correlations between the Best activity index and the content of these cytokines in the blood of the examined patients, confirm their leading role in the cascade of immune-inflammatory reactions during Crohn's disease.

scholarly journals Stem cell therapy for Crohn’s disease: systematic review and meta-analysis of preclinical and clinical studies

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ruo Wang ◽  
Qigu Yao ◽  
Wenyi Chen ◽  
Feiqiong Gao ◽  
Pan Li ◽  
...  
Keyword(s):  
Stem Cell ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Cell Therapy ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Stem Cell Therapy ◽  
Activity Index ◽  
Disease Activity Index ◽  
Control Group

Abstract Background We explored whether stem cell therapy was effective for animal models and patients with Crohn’s disease (CD). Methods We searched five online databases. The relative outcomes were analyzed with the aid of GetData Graph Digitizer 2.26 and Stata 16.0 software. The SYRCLE risk of bias tool and the MINORS tool were used to assess study quality. Results We evaluated 46 studies including 28 animal works (n = 567) and 18 human trials (n = 360). In the animal studies, the disease activity index dramatically decreased in the mesenchymal stem cell (MSC) treatment groups compared to the control group. Rats and mice receiving MSCs exhibited longer colons [mice: standardized mean difference (SMD) 2.84, P = 0.000; rats: SMD 1.44, P = 0.029], lower histopathological scores (mice: SMD − 4.58, p = 0.000; rats: SMD − 1.41, P = 0.000) and lower myeloperoxidase levels (SMD − 6.22, P = 0.000). In clinical trials, stem cell transplantation reduced the CD activity index (SMD − 2.10, P = 0.000), the CD endoscopic index of severity (SMD − 3.40, P = 0.000) and simplified endoscopy score for CD (SMD − 1.71, P = 0.000) and improved the inflammatory bowel disease questionnaire score (SMD 1.33, P = 0.305) compared to control values. CD patients maintained high remission rates for 3–24 months after transplantation. Conclusions Stem cell transplantation is a valuable supplementary therapy for CD.

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