Long-Term Effects of Bone Marrow-Derived Mesenchymal Stem Cells in Dextran Sulfate Sodium-Induced Murine Chronic Colitis

BACKGROUND/AIMS: Bone marrow-derived mesenchymal stem cells (BM-MSCs) have shown beneficial effects in experimental colitis models, but the underlying mechanisms are not fully understood. We investigated the long-term effects of BM-MSCs, particularly in mice with chronic colitis. METHODS: Chronic colitis was induced by administering 3% dextran sulfate sodium (DSS) in a series of three cycles. BM-MSCs were injected intravenously into DSS-treated mice three times during the first cycle. On day 33, the therapeutic effects were evaluated with clinicopathologic profiles and histological scoring. Inflammatory mediators were measured with real-time polymerase chain reaction. RESULTS: Systemic infusion of BM-MSCs ameliorated the severity of colitis, and body weight restoration was significantly promoted in the BM-MSC-treated mice. In addition, BM-MSC treatment showed a sustained beneficial effect throughout the three cycles. Microscopic examination revealed that the mice treated with BM-MSCs had fewer inflammatory infiltrates, a lesser extent of inflammation, and less crypt structure damage compared with mice with DSS-induced colitis. Anti-inflammatory cytokine levels of interleukin-10 were significantly increased in the inflamed colons of BM-MSC-treated mice compared with DSS-induced colitis mice. CONCLUSIONS: Systemic infusion of BM-MSCs at the onset of disease exerted preventive and rapid recovery effects, with long-term immunosuppressive action in mice with repeated DSS-induced chronic colitis.

Accuracy of three different fecal calprotectin tests in the diagnosis of inflammatory bowel disease

BACKGROUND/AIMS: Several studies have found that the measurement of fecal calprotectin is useful for the early diagnosis of inflammatory bowel disease (IBD). We compared the effectiveness of three different fecal calprotectin kits for initial diagnosis in patients with suspected IBD. METHODS: We enrolled 31 patients with IBD (18 Crohn's disease [CD], 11 ulcerative colitis [UC], and two intestinal Behçet's disease), five with irritable bowel syndrome (IBS), and five with other colitis (four infectious colitis and one intestinal tuberculosis). Diagnosis was based on clinical, laboratory, and endoscopic examinations. Fecal samples were obtained at the first diagnosis and calprotectin levels were measured using three different kits (Quantum Blue® Calprotectin, EliA™ Calprotectin, and RIDASCREEN® Calprotectin). RESULTS: The overall accuracy for differentiating IBD from IBS or other colitis was 94% and 91%, respectively, for Quantum Blue® (cutoff, 50 µg/g); 92% and 89%, respectively, for EliA™ (cutoff, 50 µg/g); and 82% and 76%, respectively, for RIDASCREEN® (cutoff, 50 µg/g). In patients with CD, the results of Quantum Blue® Calprotectin and EliA™ Calprotectin correlated significantly with levels of the Crohn's disease activity index (Spearman's rank correlation coefficient, r=0.66 and r=0.49, respectively). In patients with UC, the results of EliA™ Calprotectin correlated significantly with the Mayo score (r=0.70). CONCLUSIONS: Fecal calprotectin measurement is useful for the identification of IBD. The overall accuracies of the three fecal calprotectin kits are comparable.

Accuracy of three different fecal calprotectin tests in the diagnosis of inflammatory bowel disease

BACKGROUND/AIMS: Several studies have found that the measurement of fecal calprotectin is useful for the early diagnosis of inflammatory bowel disease (IBD). We compared the effectiveness of three different fecal calprotectin kits for initial diagnosis in patients with suspected IBD. METHODS: We enrolled 31 patients with IBD (18 Crohn's disease [CD], 11 ulcerative colitis [UC], and two intestinal Behçet's disease), five with irritable bowel syndrome (IBS), and five with other colitis (four infectious colitis and one intestinal tuberculosis). Diagnosis was based on clinical, laboratory, and endoscopic examinations. Fecal samples were obtained at the first diagnosis and calprotectin levels were measured using three different kits (Quantum Blue® Calprotectin, EliA™ Calprotectin, and RIDASCREEN® Calprotectin). RESULTS: The overall accuracy for differentiating IBD from IBS or other colitis was 94% and 91%, respectively, for Quantum Blue® (cutoff, 50 µg/g); 92% and 89%, respectively, for EliA™ (cutoff, 50 µg/g); and 82% and 76%, respectively, for RIDASCREEN® (cutoff, 50 µg/g). In patients with CD, the results of Quantum Blue® Calprotectin and EliA™ Calprotectin correlated significantly with levels of the Crohn's disease activity index (Spearman's rank correlation coefficient, r=0.66 and r=0.49, respectively). In patients with UC, the results of EliA™ Calprotectin correlated significantly with the Mayo score (r=0.70). CONCLUSIONS: Fecal calprotectin measurement is useful for the identification of IBD. The overall accuracies of the three fecal calprotectin kits are comparable.

Risk Factors for Recurrent High-Risk Polyps after the Removal of High-Risk Polyps at Initial Colonoscopy

PURPOSE: Colonoscopic polypectomy and surveillance are important to prevent colorectal cancer and identify additional relative risk factors for adequate surveillance. In this study, we evaluated risk factors related to recurrent high-risk polyps during the surveillance of patients with high-risk polyps. MATERIALS AND METHODS: We included 434 patients who had high-risk polyps (adenoma > or =10 mm, > or =3 adenomas, villous histology, or high-grade dysplasia) on the baseline colonoscopy and underwent at least one surveillance colonoscopy from 2005 to 2011 at Severance Hospital. Data regarding patient characteristics, bowel preparation and polyp size, location, number, and pathological diagnosis were retrospectively collected from medical records. Patients with recurrent high-risk polyps were compared with patients with low-risk or no polyps during surveillance. RESULTS: Patients were predominantly male (77.4%), with a mean age of 61.0+/-8.6 years and mean follow-up of 1.5+/-0.8 years. High-risk polyps recurred during surveillance colonoscopy in 51 (11.8%) patients. Results of multivariate analysis showed that male gender, poor bowel preparation, and a larger number of adenomas were independent risk factors for recurrent high-risk polyps (p=0.047, 0.01, and <0.001, respectively). Compared with high-risk polyps found during initial colonoscopy, high-risk polyps on surveillance colonoscopy had higher proportions of small adenomas, low-risk pathology, and fewer adenomas overall, but there was no difference in location. CONCLUSION: Male patients and those with poor bowel preparation for colonoscopy or higher numbers of adenomas were more likely to experience recurrent high-risk polyps.

Correlation between Soluble Triggering Receptor Expressed on Myeloid Cells-1 and Endoscopic Activity in Intestinal Behcet's Disease

PURPOSE: The serum levels of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) have recently been shown to be correlated highly with disease activity in patients with intestinal Behcet's disease (BD). However, it remains unclear whether sTREM-1 levels reflect endoscopic activity in intestinal BD. This study aimed to evaluate the correlation of sTREM-1 levels with endoscopic activity in intestinal BD. MATERIALS AND METHODS: A total of 84 patients with intestinal BD were enrolled. Endoscopic activity was compared with sTREM-1 levels as well as other laboratory findings, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). RESULTS: sTREM-1 levels were significantly increased in intestinal BD patients compared with controls (37.98+/-27.09 pg/mL vs. 16.65+/-7.76 pg/mL, p=0.002), however, there was no difference between endoscopically quiescent and active diseases (43.53+/-24.95 pg/mL vs. 42.22+/-32.68 pg/mL, p=0.819). Moreover, serum sTREM-1 levels did not differ in terms of number, shape, depth, size, margin, or type of ulcer in patients with intestinal BD. However, mean ESR and CRP levels in patients with active disease were significantly higher than those in patients with quiescent disease (p=0.001, p<0.001, respectively). In addition, endoscopic activity scores for intestinal BD were correlated significantly with both CRP levels (gamma=0.329) and ESR (gamma=0.298), but not with sTREM-1 levels (gamma=0.166). CONCLUSION: Unlike CRP levels and ESR, serum sTREM-1 levels were not correlated with endoscopic activity in patients with intestinal BD.

How Many Valid Measurements Are Necessary to Assess Liver Fibrosis Using FibroScan(R) in Patients with Chronic Viral Hepatitis? An Analysis of Subjects with at Least 10 Valid Measurements

PURPOSE: Using FibroScan(R) to obtain a reliable liver stiffness measurement (LSM) may require more than 10 valid measurements (VMs), according to the manufacturer's recommendations. However, this requirement lacks scientific evidence in support thereof. We investigated the minimal number of VMs required to assess liver fibrosis without significant loss of accuracy in patients with chronic hepatitis B (CHB) and C (CHC) and predictors of discordance between LSM and liver biopsy (LB). MATERIALS AND METHODS: Between January 2005 and December 2009, we prospectively enrolled 182 patients with CHB and 68 patients with CHC who were to undergo LB and LSM before starting antiviral treatment. Only LSMs with at least 10 VMs were considered reliable. The Batts and Ludwig scoring system was used for histologic assessment. RESULTS: The mean age and body mass index were 46.0 years and 23.4 kg/m2 in patients with CHB and 49.7 years and 23.1 kg/m2 in those with CHC, respectively. The median elasticity scores from the first 3, first 5, and all VMs taken significantly predicted fibrosis stages > or =F2 and F4 (all p0.05 by DeLong's method). Alanine aminotransferase (ALT) was the only predictor of discordance in fibrosis stage as estimated by the median elasticity score from the first 3 VMs and by LB in patients with CHB, whereas no significant predictor was identified in those with CHC. CONCLUSION: After comparison of patients who had more than 10 valid measurements for LSM, three VMs may be enough to assess liver fibrosis using LSM without significant loss of accuracy in patients with CHC and patients with CHB. However, ALT should be considered when interpreting LSM for patients with CHB.

Overlap Syndrome of Antisynthetase Syndrome and Rheumatoid Arthritis: A Case Report / 대한내과학회지

The antisynthetase syndrome is characterized by anti-Jo-1 antibody production, interstitial lung disease, inflammatory muscle disease, and, in many cases, fever, polyarthritis, Raynaud's phenomenon, and mechanic's hands. Joint signs and symptoms occur in up to 90% of patients with antisynthetase syndrome, occasionally as the initial manifestations. Although visual inspection of the hands shows changes that are highly suggestive of rheumatoid arthritis, notable differences exist. Antisynthetase syndrome is a predominantly nonerosive arthropathy with subluxations of the distal interphalangeal joints. It manifests as overlap syndrome with other connective tissue diseases. However, overlap syndrome of antisynthetase syndrome and rheumatoid arthritis is rare. We treated a 51-year-old male patient with overlap syndrome of antisynthetase syndrome and rheumatoid arthritis, and report the case with a review of the literature.

ANCA-associated Vasculitis after Scrub Typhus / 감염과화학요법

Anti-neutrophilic cytoplasmic antibody (ANCA)-associated vasculitis is a primary systemic vasculitis that affects the small vessels, and ANCA is involved as the common pathogenesis. Environmental factors such as infectious agents have been considered to play a role in triggering the autoimmunity. We report here on a case of ANCA-associated vasculitis that developed after scrub typhus. A 64-year-old male was admitted because of fever, chills, pain, weakness and hypoesthesia of his calves. He was diagnosed as having scrub typhus based on the findings of an eschar and the positive serum anti-orientia antibody. The fever continued despite the antibiotic treatment. Neurologic symptoms such as numbness, hypoesthesia and weakness began to develop in the hands, feet and calves with a persisting fever. The nerve conduction velocity study revealed mononeuritis multiplex of the superficial peroneal nerve and the median nerve. Microscopic hematuria then additionally developed, and the serology showed a positive myeloperoxidase (MPO) test. A nerve biopsy was conducted on the left superficial peroneal nerve and the result showed non-infectious systemic vasculitis of the medium-small arteries. He was diagnosed as having microscopic polyangiitis along with ANCA associated vasculitis. The fever resolved and the neurologic symptoms began to improve after steroid pulse treatment (methylprednisolone 1 g/day). The neuropathy gradually improved after discharge. We presume that the ANCA-associated vasculitis was triggered by scrub typhus.

Clinical Experience of Thalidomide in the Treatment of Korean Patients with Intestinal Behcet's Disease: Pilot Experience in a Single Center

Intestinal Behcet's disease (BD) often leads to severe complications, such as perforation or massive bleeding, and therefore is one of the major causes of morbidity and mortality. As thalidomide has been identified and its anti-inflammatory and immunomodulatory properties clarified, this drug has been used in cases of systemic BD with some success. Herein we report a case series of four patients with intestinal BD to share our clinical experience with thalidomide treatment. We studied the effects of thalidomide in four patients who had a chronic relapse of intestinal BD requiring the frequent use of systemic steroids due to refractoriness to prior treatments, such as 5-aminosalycylic acid and immunosuppressants. Pre- and post-treatment clinical and laboratory data, including clinical symptoms, laboratory data, disease activity index for intestinal BD, and thalidomide toxicity were recorded. Three of the four patients had a clinical and radiologic improvement after thalidomide treatment and all of the patients discontinued steroid therapy. Although two patients tolerated thalidomide, two patients could not continue the treatment because they suffered from edema and neutropenia. Thalidomide could be considered a therapeutic option for the treatment of intestinal BD.

Clinical Experience of Thalidomide in the Treatment of Korean Patients with Intestinal Behcet's Disease: Pilot Experience in a Single Center

Intestinal Behcet's disease (BD) often leads to severe complications, such as perforation or massive bleeding, and therefore is one of the major causes of morbidity and mortality. As thalidomide has been identified and its anti-inflammatory and immunomodulatory properties clarified, this drug has been used in cases of systemic BD with some success. Herein we report a case series of four patients with intestinal BD to share our clinical experience with thalidomide treatment. We studied the effects of thalidomide in four patients who had a chronic relapse of intestinal BD requiring the frequent use of systemic steroids due to refractoriness to prior treatments, such as 5-aminosalycylic acid and immunosuppressants. Pre- and post-treatment clinical and laboratory data, including clinical symptoms, laboratory data, disease activity index for intestinal BD, and thalidomide toxicity were recorded. Three of the four patients had a clinical and radiologic improvement after thalidomide treatment and all of the patients discontinued steroid therapy. Although two patients tolerated thalidomide, two patients could not continue the treatment because they suffered from edema and neutropenia. Thalidomide could be considered a therapeutic option for the treatment of intestinal BD.

Risk Factors for Treatment Failure and Recurrence after Metronidazole Treatment for Clostridium difficile-associated Diarrhea

BACKGROUND/AIMS: The incidence of treatment failure or recurrence of Clostridium difficile-associated diarrhea (CDAD) following metronidazole treatment has increased recently. We studied the treatment failure, recurrence rate, and risk factors predictive of treatment failure and recurrence after metronidazole treatment for CDAD. METHODS: We retrospectively identified consecutive patients who were admitted and treated for CDAD at a single tertiary institution in Korea over a recent 10-year period (i.e., 1998-2008). RESULTS: Metronidazole was administered as the initial treatment to 111 of 117 patients (94.9%) with CDAD. Fourteen patients (12.6%) had no clinical response to the metronidazole treatment, and in 13 patients (13.4%) CDAD recurred after successful metronidazole treatment. Diabetes mellitus (p=0.014) and sepsis (p=0.002) were independent risk factors for metronidazole treatment failure. Patients who had received surgery within 1 month before CDAD developed were more likely to experience a recurrence after metronidazole treatment (p=0.032). Vancomycin exhibited a higher response rate after treatment failure, and metronidazole showed a reasonable response rate in the treatment of recurrence. Treatment failure and recurrence rates increased with time after metronidazole treatment for CDAD over the 10-year study period. CONCLUSIONS: Our data suggest that diabetes mellitus and sepsis are independent risk factors for metronidazole treatment failure, and that operation history within 1 month of development of CDAD is a predictor of a recurrence after metronidazole treatment.

Colitis Cystica Profunda Masquerading as a Pneumatosis Cystoides Intestinalis: A Case Report

Colitis Cystica Profunda (CCP) is an uncommon and benign disease entity characterized by mucoid cysts located in the submucosal layer of the colon. It can mimic cystic submucosal tumors or mucinous adenocarcinoma and is usually located in the rectum. CCP is found in the ascending colon less frequently. CCP manifesting as multiple cystic tumors, similar to pneumatosis cystoides intestinalis, has not yet been reported. Recently, a case of CCP mimicking pneumatosis cystoides intestinalis in the ascending colon was treated. Here this case is reported and the literature reviewed.