Mónika Szűcs

Fecal MMP-9: A new noninvasive differential diagnostic and activity marker in ulcerative colitis

Background:Ulcerative colitis (UC) is characterized by frequent relapses, with the presence of colorectal inflammation and mucosal lesions. Matrix-metalloprotease 9 (MMP-9) is elevated in colonic biopsies, urine, and blood plasma of UC patients. MMP-9 has been suggested as a predictor of UC in the urine of children; however, 20% of the controls tested positive. So far, fecal MMP-9 levels have never been measured. Our aims were: 1) to compare fecal MMP-9 levels in UC patients to control subjects and a functional gastrointestinal disorder characterized by diarrhea (IBS-D); 2) to test the correlation between UC disease activity and fecal levels of MMP-9; and 3) to correlate fecal MMP-9 levels with a known fecal marker of UC activity, calprotectin. Methods:UC (n = 47), IBS-D (n = 23) patients, and control subjects (n = 24) provided fecal samples for MMP-9 analysis. In UC patients, disease severity was evaluated by the Mayo score. Fecal MMP-9 and calprotectin levels were measured by enzyme-linked immunosorbent assay and lateral flow assay, respectively. Results:MMP-9 was undetectable or ⩽0.22 ng/mL in the feces of all controls and IBS-D patients. In UC patients, fecal MMP-9 levels significantly correlated with the overall Mayo score (P < 0.001), the endoscopic score (P < 0.001), and the serum C-reactive protein levels (P = 0.002). Additionally, in UC patients fecal MMP-9 levels showed a significant correlation with a known disease activity marker, fecal calprotectin (P = 0.014). Conclusions:These results highlight fecal MMP-9 as a useful tool in the differential diagnosis of diarrheic disorders and in the noninvasive evaluation of disease activity and mucosal healing in UC.

The Diagnostic Value of a New Fecal Marker, Matrix Metalloprotease-9, in Different Types of Inflammatory Bowel Diseases

BACKGROUND Only limited data are available regarding the diagnostic accuracy of fecal matrix metalloprotease-9 [MMP-9] for inflammatory bowel disease [IBD]. The aims of our study were to assess the diagnostic accuracy of fecal MMP-9 in patients with active Crohns disease [CD], ulcerative colitis [UC], and pouchitis, and to compare the diagnostic accuracy of fecal MMP-9 and fecal calprotectin [CP] in IBD. METHODS Stool and blood samples were collected in 50 CD, 54 UC, and 34 ileal pouch-anal anastomosis patients before control endoscopies were performed. Biopsies were taken for histologic purposes. The activities of CD, UC, and pouchitis were defined with the use of clinical, endoscopic, and histologic activity scores. Fecal CP and MMP-9 levels were quantified by enzyme-linked immunosorbent assay. RESULTS Active CD, UC, and pouchitis were detected in 38%, 54%, and 29% of the patients, respectively. A significant correlation was revealed between fecal CP and the clinical activities of CD and UC, and between fecal CP and the endoscopic activity of UC and pouchitis. Fecal MMP-9 did not correlate with any of the activity indices of CD; however, strong associations were shown between fecal MMP-9 and clinical, endoscopic, and histologic activities of both UC and pouchitis. CONCLUSIONS This is the first study assessing the diagnostic accuracy of MMP-9 in different types of IBD. Our results showed that fecal MMP-9 has high sensitivity in the detection of endoscopically active UC and pouchitis. These non-invasive methods help assess intestinal inflammation.

Utility of serum TNF-α, infliximab trough level, and antibody titers in inflammatory bowel disease

AIM To assess tumor necrosis factor-α (TNF-α), infliximab (IFX) concentrations, and antibodies against IFX molecules in patients with inflammatory bowel disease (IBD) who develop loss of response, side effects, or allergic reaction during anti TNF-α therapy. METHODS Blood samples of 36 patients with response loss, side effects, or hypersensitivity to IFX therapy (Group I) and 31 patients in complete clinical remission (Group II) selected as a control group were collected to measure trough serum TNF-α level, IFX, and anti-IFX antibody (ATI) concentration. We examined the correlation between loss of response, the development of side effects or hypersensitivity, and serum TNF-α, IFX trough levels, and ATI concentrations. RESULTS The serum TNF-α level was shown to be correlated with the presence of ATI; ATI positivity was significantly correlated with low trough levels of IFX. ATIs were detected in 25% of IBD patients with loss of response, side effects, or hypersensitivity, however no association was revealed between these patients and antibody positivity or lower serum IFX levels. Previous use of IFX correlated with the development of ATI, although concomitant immunosuppression did not have any impact on them. CONCLUSION On the basis of the present study, we suggest that the simultaneous measurement of serum TNF-α level, serum anti TNF-α concentration, and antibodies against anti TNF-α may further help to optimize the therapy in critical situations.

Efficacy and Safety of Adalimumab in Ulcerative Colitis Refractory to Conventional Therapy in Routine Clinical Practice.

BACKGROUND AND AIM Adalimumab [ADA] was approved for the treatment of ulcerative colitis [UC] refractory to conventional therapy in 2012 in Europe. Due to the observed discrepancies between clinical trials and practice, data on the outcome of ADA therapy are really needed from the real life. The aim of this study was to estimate the short- and long-term efficacy and safety of ADA in UC patients from each Hungarian biological centre. PATIENTS AND METHODS This prospective study consisted of UC patients treated with ADA in 10 Hungarian inflammatory bowel disease centres. The primary endpoints of the study were rates of continuous clinical response, remission, non-response and loss of response at Weeks 12, 30, and 52.The secondary endpoints included mucosal healing at Week 52 and the comparison of the efficacy of ADA between biological naive and infliximab [IFX]-treated groups. Colonoscopy was performed before starting the therapy and at Week 52. RESULTS In all, 73 active UC patients were enrolled in the study: 67.1% of the patients received previous IFX therapy; 75.3% of the patients showed short-term clinical response at Week 12. The probability of maintaining ADA was 48.6% at Week 52 with a continuous clinical response in 92% of these remaining patients. Mucosal healing was achieved in 48.1% of the patients at Week 52. Escalation of ADA was performed in 17.6%, and minor side effects developed in 4% of the patients; 5.4% of the patients underwent colectomy during the 1-year treatment period. CONCLUSION UC is a progressive disease that may need early aggressive therapy to prevent structural and functional complications. The results of our study demonstrated the favourable efficacy of short- and long-term ADA treatment for patients with UC.

Long-term outcome of cyclosporin rescue therapy in acute, steroid-refractory severe ulcerative colitis.

Background Although cyclosporin is effective in severe ulcerative colitis (UC), long-term colectomy rate varies between 60 and 88% among patients in whom cyclosporin initially induced remission. The aim of our study was to evaluate the long-term outcome and the optimal duration of cyclosporin therapy in acute, severe UC. Methods A total of 73 patients underwent i.v. cyclosporin therapy for a steroid refractory flare up of UC between 1998 and 2009. All patients were treated with 1 mg/kg i.v. methylprednisolone for 3–7 days before the administration of cyclosporin. Patients received i.v. cyclosporin of 4–5 mg/kg for 5 days following oral treatment. Results The mean follow up after the initiation of cyclosporin was 4.2 years. There were 20 patients who underwent early colectomy. Cyclosporin had to be discontinued due to side effects in 22 patients. Cyclosporin failed and late colectomy was performed in 14 of the 53 responders. Duration of cyclosporin treatment was significantly longer in those who avoided colectomy. The probability of avoiding colectomy proved to be 66% in case of 1-year treatment period with cyclosporin. The longer treatment period resulted in longer colectomy-free disease course. Conclusions Cyclosporin is effective in acute, severe UC during long-term follow up. Our data suggest that the longer cyclosporin is used, the more it is possible to avoid colectomy in the future.

Absolute beat-to-beat variability and instability parameters of ECG intervals: biomarkers for predicting ischaemia-induced ventricular fibrillation

Predicting lethal arrhythmia liability from beat‐to‐beat variability and instability (BVI) of the ECG intervals is a useful technique in drug assessment. Most investigators use only arrhythmia‐free ECGs for this. Recently, it was shown that drug‐induced torsades de pointes (TdP) liability can be predicted more accurately from BVI measured irrespective of rhythm, even during arrhythmias (absolute BVI). The present study tested the broader applicability of this assessment by examining whether absolute BVI parameters predict another potential lethal arrhythmia, ischaemia‐induced ventricular fibrillation (VF).

A pilot study on faecal MMP-9: a new noninvasive diagnostic marker of colorectal cancer.

Background:Colorectal cancer (CRC) is one of the leading malignancies worldwide, therefore cheap noninvasive screening methods are of great importance. Matrix-metalloproteinase-9 (MMP-9) has a role in the progression of CRC, and its level is elevated in tumour biopsies. Faecal MMP-9 levels are increased in active ulcerative colitis patients, but in CRC patients, they have never been measured. We aimed to assess the faecal MMP-9 levels in patients undergoing total colonoscopy according to endoscopic and histological diagnosis.Methods:One hundred and nine patients provided faecal samples for MMP-9 analysis. A total colonoscopy was performed; suspicious lesions were evaluated by histology. Faecal MMP-9 levels were measured by ELISA.Results:The number of patients allocated to different groups were: negative/diverticulosis: 34 (referred to as controls); hyperplastic polyps: 15; adenomas: 32 (22 at high risk); and CRC: 28. Faecal MMP-9 was significantly increased in CRC compared with all other groups (P<0.001). Faecal MMP-9 was suitable to distinguish CRC patients from controls (sensitivity: 89.3%; specificity: 91.2%). By means of a lower cutoff level, faecal MMP-9 identified high-risk adenomas besides CRC (sensitivity: 76%; specificity: 85.3%). This lower cutoff level screened 59% of high-risk adenomas.Conclusions:Faecal MMP-9 may be a promising new noninvasive marker in CRC.

Prospective Comparison of Magnetic Resonance Imaging, Transrectal and Transperineal Sonography, and Surgical Findings in Complicated Perianal Crohn Disease

Magnetic resonance imaging (MRI) and transrectal sonography are the two accepted imaging modalities for evaluation of perianal fistulas and abscesses. Transperineal sonography is a new technique that is easy to learn and can be performed at any time. The purpose of this study was to prospectively compare the diagnostic accuracy of MRI, transrectal sonography, and transperineal sonography with surgical findings in patients with perianal Crohn disease.

Faecal matrix metalloprotease-9 is a more sensitive marker for diagnosing pouchitis than faecal calprotectin: results from a pilot study.

Background: Potential non-invasive markers of pouchitis would have a great deal of significance within clinical practice. Aim: This study is aimed at assessing the diagnostic accuracy of fecal calprotectin and matrix metalloprotease-9 as potential markers in patients both with and without pouchitis. Patients and methods: Stool and blood samples were collected from 33 ileal pouch-anal anastomosis patients before a follow-up pouchoscopy. Biopsy samples were taken for histological purposes. The presence of cuffitis and stenosis was evaluated with an endoscopy. Calprotectin and matrix metalloprotease-9 were quantified with an enzyme-linked immunosorbent assay. Results: Pouchitis was detected in 30.3% of the patients. The levels of fecal calprotectin and matrix metalloprotease-9 increased significantly in patients with pouchitis. The sensitivity and specificity of matrix metalloprotease-9 was higher than that of fecal calprotectin. Only matrix metalloprotease-9 correlated significantly with the severity of pouchitis. Discussion: Fecal matrix metalloprotease-9 has a high specificity in the diagnosis of pouchitis.

Pregnancy does not affect fecal calprotectin concentration in healthy women

BACKGROUND/AIMS Noninvasive activity markers are extremely important in conditions, such as pregnancy, when endoscopy is not recommended. The aim of this prospective study was to determine fecal calprotectin (FC) concentrations in healthy non-pregnant and pregnant women and in patients with inflammatory bowel disease (IBD). MATERIALS AND METHODS Healthy pregnant and non-pregnant women and patients with active and inactive IBD were prospectively enrolled in this study. Demographic and clinical parameters and clinical disease activity scores in patients with IBD were recorded. Blood and stool samples of every patient were obtained to determine C-reactive protein and FC levels. FC levels were measured with a quantitative lateral flow assay. RESULTS One hundred and thirty-five subjects were enrolled in the study (24 non-pregnant and 48 pregnant healthy women, 40 non-pregnant patients with active IBD and 23 non-pregnant patients with inactive IBD). FC was significantly higher in active IBD patients than in pregnant (p<0.001) and non-pregnant healthy women (p<0.001). No difference could be detected in FC concentrations between pregnant and non-pregnant healthy women. CONCLUSION Since FC levels remained unchanged during pregnancy, it may be a useful noninvasive diagnostic tool in pregnancy for monitoring mucosal inflammation.