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Aim: We have previously shown that CRP < 2.9 mg/L is a better predictor of endoscopic remission (ER) than CRP < 5 mg/L in ulcerative colitis (UC). Here, we prospectively evaluate CRP and FCP cut-offs and compare them in predicting ER and histological remission (HR) in UC. Method: One hundred thirty-five steroid-free UC patients were evaluated prospectively. ER was defined as Mayo endoscopic sub-score 0-1. In colonoscopy, the colon was evaluated as seven segments: rectum, sigmoid, descending, proximal-transverse, distal-transverse, ascending colon, and cecum. Two biopsies of each segment were evaluated for histological inflammation and graded using the Nancy and Geboes scores. All segment biopsies with Nancy < 1 and Geboes < 2 were defined as HR. Results: The optimum cut-off values for FCP and CRP were 120 μg/g and 2.75 mg/L for ER, respectively. AUC values of FCP and CRP were similar for ER and Mayo-0 disease in ROC analysis. CRP and FCP also had similar performances with these cut-offs regarding ER. While CRP was a predictor to assess the extensiveness of active UC, FCP was not. ROC analysis showed no difference between CRP and FCP regarding HR. Cut-off values for HR were 2.1 mg/L and 55 μg/g for CRP and FCP, respectively. CRP and FCP, in combination with the mentioned cut-off values, detected ER and HR in nearly 2/3 and ½ of the patients, respectively, with high specificity. Conclusions: Reappraised CRP (ER: 2.75 mg/L, HR: 2.1 mg/L) has as much diagnostic contribution as relevant FCP in predicting ER and HR and contributes more to revealing the proximal extension in active colitis compared to FCP. Relevant CRP and FCP combinations may improve the prediction rates.

Mixing performance in reactors producing biogas through anaerobic digestion is one of the parameters that directly affect biogas yield. The most commonly used mixing model for bioreactors in biogas-production processes is mechanical mixing. In the present study, we focus on the geometry of the tank, where the mechanical mixing actually takes place. In this context, by using the six-blade standard Rushton impeller in two different types of tank, flow patterns involving velocity, dead zone volume, turbulent kinetic energy, and turbulent eddy dissipation rate in the angular velocity range of 25-100 rpm were observed, and the possible effects of the results on biogas production were interpreted. A new impeller design was proposed that maximizes the interface between the fluid inside the reactor tank and the impeller, which has the potential to reduce the dead zone volume to significantly lower levels. Our results showed that the lowest dead zone volume was achieved for a 60° slope reactor tank compared to the conventional 90° slope reactor tank at an angular velocity of 100 rpm. The dead zone volume decreased to 0.000094 m 3 at 100 rpm in the 60° slope reactor tank with a total volume of 0.0305 m 3 , which by comparison was 0.000374 m 3 in the 90° slope reactor tank. The magnitudes of both maximum turbulent kinetic energy and maximum turbulent eddy dissipation were higher in the 60° slope reactor tank at all angular velocities examined, which would be expected to enhance mixing performance. It is hoped that the reader will benefit from the results of this study; however, further studies should be conducted on the use of actual biowaste as the working fluid instead of water., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Treatment response may be variable across organ manifestations of Behçet syndrome (BS). We aimed to determine the frequency of de novo manifestations during adalimumab treatment., Methods: We conducted a chart review of all BS patients who received adalimumab in our center between 2008 and 2023. Demographic data, reasons for initiating adalimumab, concurrent medications, previous treatments, and outcomes were recorded. We defined de novo manifestations as new BS manifestations that occurred for the first time during treatment with adalimumab. For patients with vascular involvement, a new vascular event at another vessel was also considered as a de novo manifestation., Results: Among the 335 patients, a de novo manifestation developed in 14 (4%) patients. De novo manifestations were vascular involvement in 5 patients, arthritis in 3, anterior uveitis in 2, nervous system involvement in 2, gastrointestinal involvement in 1, and epididymitis in 1 patient. The primary reasons for adalimumab treatment were vascular involvement in 5 patients, uveitis in 4, arthritis in 3, mucocutaneous involvement in 1, and epididymitis in 1 patient. Upon the development of de novo manifestation, adalimumab was switched to another biologic in 4 patients, dose was intensified in 3, colchicine, conventional immunosuppressives, and/or glucocorticoids were added in 5, and topical eye drops were added in 2 patients, leading to remission of de novo manifestations in all patients., Conclusion: De novo manifestations were infrequent (4%) among BS patients treated with adalimumab. Of these, 57% were major organ involvement, mainly vascular involvement. None of the patients developed posterior uveitis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Non-steroidal anti-inflammatory drug (NSAID) use may cause diaphragm-like lesions in the bowel. Although NSAID-enteropathy is among the causes of protein-losing enteropathy (PLE), intractable hypoalbuminemia is rare., Case Report: Here, we discuss a case of NSAID-enteropathy with a diaphragm-like disease that presented with Protein Losing Enteropathy (PLE) rather than obstruction. The hypoalbuminemia recovered immediately after resection of the obstructive segment, despite ongoing annular ulcerations in the early postoperative period. Thus, it was not clear whether obstructive mechanisms influenced resistant hypoalbuminemia besides the ulcers. We also reviewed the English-written literature for "diaphragm-type lesion, NSAID-enteropathy, obstruction, and protein-losing enteropathy". We noted that the role of obstruction in the pathophysiology of PLE was not clear., Conclusions: As our case and a couple of cases reported in literature, slow-onset obstructive pathology seems to contribute to well-known factors: inflammatory response, exudation, tight-junction dysfunction, and increase in permeability in the physiopathology of NSAID-induced PLE. Factors such as distention-induced low-flow ischemia and reperfusion, cholecystectomy-related continuous bile flow, bacterial overgrowth-related bile deconjugation and concomitant inflammation are among other potential influencers. The possible role of a slow-onset obstructive pathology in the physiopathology of NSAID-induced and other PLE needs to be further elucidated.

Objectives: Infliximab (IFX) is increasingly being used for the treatment of severe manifestations of Behçet's syndrome (BS). However, emergence of new manifestations has also been occasionally reported during IFX treatment. We aimed to assess the frequency of new manifestations in our BS patients treated with IFX., Methods: A chart review was conducted to identify all BS patients treated with IFX in our clinic between 2004 and 2020. Demographic data, indications for IFX initiation, concomitant treatments and outcomes were recorded. A new manifestation was defined as the emergence of a new organ involvement or mucocutaneous manifestation developing for the first time during IFX treatment or within 12 weeks after the last infusion of IFX., Results: Among our 282 patients who used IFX, 19 (7%) patients had developed a total of 23 new manifestations during a mean follow-up of 20.0 (15.3) months. Patients with vascular involvement were more likely to develop a new manifestation (12/19, 63%). Initial manifestations that required IFX were in remission at the time of new manifestation in 14/19 patients. IFX treatment was intensified (n = 6) and/or glucocorticoids, immunosuppressives or colchicine was added to IFX (n = 21). IFX was switched to another agent for the remaining manifestations (n = 8). These treatment modifications led to remission in 17/19 patients., Conclusion: New manifestations developed during IFX treatment in 7% of our patients with BS. They could be managed by intensifying IFX treatment or adding other agents in the majority of these manifestations., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

It is assumed that in candidates for TNF-alpha inhibitor (TNFi) treatment, tuberculin skin test (TST) may be unreliable, since BCG vaccination causes false positive and drugs cause false negative results, favoring the use of Quantiferon or T-spot assays. However, these tests may not be readily available in all parts of the world. We aimed to determine the reliability of TST with respect to BCG vaccination and drugs in candidates for TNFi treatment, and how isoniazid is tolerated, assuming that the use of TST would result in increased isoniazid use. We included 1031 adult patients who were prescribed a TNFi for the first time. We analysed the association of BCG and drugs with TST and Quantiferon results, the determinants of a positive TST, and evaluated the tolerability of isoniazid. BCG vaccination and male sex were associated with positive TST (OR 3.56, 95% CI 1.98-6.41 and OR 2.54, 95% CI 1.75-3.68, respectively), while prednisolone and azathioprine were associated with negative TST (OR 0.63, 95% CI 0.43-0.91 and OR 0.40, 95% CI 0.11-0.76). Isoniazid was prescribed to 684 (66.3%) patients and had to be discontinued in 12.2% of these before 9 months, most commonly due to hepatotoxicity (44%). One patient developed tuberculosis despite isoniazid use. BCG vaccination may be associated with false positive TST, despite a long time since vaccination in candidates for TNFi treatment. Prednisolone and azathioprine use were associated with negative TST. Despite the high frequency of isoniazid use associated with using TST instead of QTF, isoniazid was generally well tolerated., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

BACKGROUND Renal involvement can complicate the course of inflammatory bowel disease (IBD). In this study, we aimed to analyze the extent of renal manifestations in patients with IBD (Crohn disease or ulcerative colitis) during the biologic era. MATERIAL AND METHODS Patients diagnosed with and followed up for IBD for a period covering 16 years were retrospectively analyzed. Patients who received IBD diagnosis with clinical, endoscopic, and histopathological findings and were older than 18 years were enrolled in the study. Demographic, clinical, laboratory, and treatment data were retrieved from the patients' medical records. RESULTS Of the 1874 patients analyzed, the diagnosis was ulcerative colitis in 1055 patients and Crohn disease in the remaining 819. Renal manifestations were found in 105 patients (5.6%), 55 (6.7%) of whom were diagnosed with Crohn disease and 50 (4.7%) with ulcerative colitis. Renal calculi was the most common renal manifestation for both Crohn disease and ulcerative colitis. Renal manifestations were related to disease activity and surgical resection history in patients with Crohn disease, whereas no such relationship was found in patients with ulcerative colitis. CONCLUSIONS Renal manifestations may be seen in up to 6% of patients with IBD, and patients with Crohn disease seems to have more risk than do patients with ulcerative colitis. Nephrolithiasis is the most common form of renal involvement in IBD and is closely associated with disease activity. This relationship between IBD and renal manifestations should be considered, especially when there are subtle renal symptoms.

Aim: Most patients with ulcerative colitis (UC) with active mucosal disease have a lower C-reactive protein (CRP) level than the classic accepted cutoff level (≤5 mg/l). We aimed to predict the mucosal remission in UC with an optimal cutoff level of CRP when mucosal activity and extensiveness of UC were both considered., Method: In this retrospective study, we evaluated CRP values and their relation to mucosal extension and UC activity in 331 colonoscopic examinations performed between December 2016 and March 2019. Endoscopic activity and disease extension were assessed using Mayo scores and the Montreal classification., Results: The Mayo 2 and 3 groups' CRP values were significantly higher when compared with Mayo 0-1 between values of E1 and both E2 and E3 with an increasing trend. The standard CRP cutoff level ≤5 mg/l only yielded 55% specificity in predicting mucosal remission. In the ROC analysis, a CRP cutoff level ≤2.9 mg/l predicted an overall mucosal remission (Mayo 0-1) with 77% sensitivity and 80% specificity, and ≤1.9 mg/l predicted Mayo-0 with 70% sensitivity and specificity. In the clinical remission subgroup, the overall CRP cutoff level was even lower, at ≤1.58 mg/l., Conclusion: An overall CRP cutoff level ≤2.9 mg/l predicts mucosal remission in UC better than the standard cutoff ≤5 mg/l. Mucosal remission in stable clinical remission may present with an even lower CRP level. An increasing trend in the CRP level from E1 through E3 even in mucosal remission suggests that both histological inflammation and extensiveness may have some influence on a CRP-based prediction of endoscopic remission., (© 2021 The Association of Coloproctology of Great Britain and Ireland.)

Objective: The aim of the study was to identify the frequency of azathioprine-induced acute pancreatitis (AZA-AP) and related factors., Methods: Seven hundred eighty-seven inflammatory bowel disease (IBD) patients on AZA therapy were retrospectively analyzed. Azathioprine-induced AP was diagnosed with positive imaging and/or an at least 3-fold increased amylase level, in presence of typical abdominal pain. The AZA-AP group was compared with patients on AZA therapy with no history of pancreatitis and 4 numerical adjacent cases with the same diagnosis were selected (group B)., Results: Fifty-four patients developed gastrointestinal symptoms (6.9%); however, only half of them (26 of 54) had pancreatitis, except 1, all within the first 2 months under AZA. When the AZA-AP group was compared with group B, only budesonide usage and active smoking were significantly more common in group A (46.2% vs 25%, P = 0.034, and 77% vs 51%, P = 0.017, respectively). Active smoking was the only independent risk factor for AZA-AP development (odds ratio, 3.208 [95% confidence interval, 1.192-8.632])., Conclusions: All IBD patients developed AZA-AP nearly all within the first 2 months. Azathioprine intolerance may be a hidden diagnosis in at least half of the patients with AZA-AP symptoms. All smoker IBD patients should be monitored closely for AZA-AP development., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Immunogenicity of tumor necrosis factor alpha inhibitors (TNFis) has been recognized as an important problem that may cause loss of efficacy and adverse events such as infusion reactions. TNFis are being increasingly used among patients with Behçet syndrome (BS) and scarce data exist on this topic., Objective: We aimed to investigate the prevalence of anti-infliximab (IFX) antibodies in patients with Behçet syndrome together with suitable controls., Methods: We collected serum samples from 66 consecutive Behçet syndrome patients (51 M, 15 F, mean age 37 ± 9 years) who were treated with IFX. Additionally, similarly treated 27 rheumatoid arthritis, 53 ankylosing spondylitis, 25 Crohn's disease patients, and 31 healthy subjects were included as controls. Samples were collected just before an infusion, stored at -80°C until analysis, and serum IFX trough levels and anti-IFX antibodies were measured by ELISA. We used a cut-off value of 1 μg/ml for serum IFX trough level, extrapolating from rheumatoid arthritis studies., Results: Anti-IFX antibodies were detected in four (6%) Behçet syndrome, five (18.5%) rheumatoid arthritis, three (12%) Crohn's disease, and one (2%) ankylosing spondylitis patient. The median serum IFX trough level was significantly lower in patients with anti-IFX antibodies compared to those without antibodies [2.32 (IQR: 0.6-3.6) vs. 3.35 (IQR: 1.63-5.6); p = 0.019]. The serum IFX trough level was lower than the cut-off value in 6/13 (46%) patients with anti-IFX antibodies and in 25/158 (16%) patients without anti-IFX antibodies (p = 0.015). Among the four Behçet syndrome patients with anti-IFX antibodies, two experienced relapses and two had infusion reactions., Conclusions: Immunogenicity does not seem to be a frequent problem in Behçet syndrome patients treated with IFX, but may be associated with relapses and infusion reactions, when present., Competing Interests: GH has received grant/research support from Celgene and has served as a speaker for AbbVie, Celgene, Novartis, and UCB Pharma. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Esatoglu, Akkoc-Mustafayev, Ozguler, Ozbakır, Nohut, Cevirgen, Hamuryudan, Hatemi, Celik, Yazici and Hatemi.)

The association between myelodysplastic syndrome (MDS) and Behçet syndrome (BS) is recognized for over 25 years. High frequency of trisomy 8 and intestinal ulcers are striking features of this association. There are no recommendations for how these patients should be treated. A systematic literature review was performed in PubMed using the keyword combination "(((((intestinal) OR gastrointestinal) OR ulcer) OR Behcet*)) AND ((myelodysplastic syndrome) OR MDS)" in March 2019. Our aim was to gain insight regarding clinical responses to individual treatment modalities. A recent case was also presented and included in the analysis. Data from 41 articles reporting on a total of 53 patients carried adequate information to assess treatment responses. Glucocorticoids provided benefit in 23 of 43 patients. Azacitidine, decitabine, thalidomide, and cyclosporine contributed to a clinical improvement in 4/6, 2/3, 3/4, and 5/8 patients respectively. Hematopoietic stem cell transplantation was successful in 9 of 13 patients. With the use of TNF inhibitors, azathioprine, and mesalamine derivatives, clinical improvement was observed in 3/11, 0/4, and 6/18 patients respectively. Patients with MDS and BS-like features who are resistant to glucocorticoids have so far benefited more from treatment approaches directed at MDS, rather than the immunosuppressive agents used for BS.

Objectives: Case reports and series suggest that Takayasu's arteritis (TAK) can co-exist with other inflammatory disorders. We conducted a formal study to look specifically at the frequency of such inflammatory disorders in a large cohort of TAK followed by a single tertiary centre., Methods: There were 238 patients registered with a diagnosis of TAK. Of these, 19 died, 18 were lost to follow-up and 3 did not wish to respond to our questionnaire. The remaining 198 (175 F/23 M) patients were called back at the outpatient clinic. A standardised form sought whether the patient was also diagnosed with inflammatory bowel disease (IBD), ankylosing spondylitis (AS), Behçet's syndrome (BS), autoimmune or any other inflammatory disorder. The presence of skin-mucosa lesions, inflammatory eye disease and inflammatory back pain were also specifically sought for., Results: We identified 37 (19%) patients with inflammatory bowel disease (n=12, 6%), ankylosing spondylitis (n=15, 8%) or Behçet's syndrome (n=10, 5%). Thirteen (6.5%) patients had systemic or localised autoimmune disease and 9 (4.5%) miscellaneous inflammatory diseases. Among the 139 patients without any concomitant disease, inflammatory back pain (n=49, 35%) was the most common feature, followed by recurrent oral ulcer (n=20, 14%) erythema nodosum (n=17, 12%), arthritis (n=12, 9%) papulopustular lesions (n=8, 6%) and uveitis/scleritis (n=6, 4%). Only 64 patients (32%) did not have any concomitant disease/condition or specific clinical feature., Conclusions: TAK does co-occur with IBD, AS and less frequently with BS in about 1/5 of the patients, at least in a hospital setting. There is no clear temporal pattern. The high prevalence of inflammatory back pain in the dorsal spine in TAK needs further scrutiny.

Objectives: The aim of this systematic review was to inform the update of European League Against Rheumatism (EULAR) Recommendations for the management of Behçet's syndrome (BS), on the evidence for the treatment of skin, mucosa and joint involvement of BS., Methods: A systematic literature search, data extraction, statistical analyses and assessment of the quality of evidence were performed according to a pre-specified protocol using the PRISMA guidelines. Studies that assessed the efficacy of an intervention in comparison to an active comparator or placebo for oral ulcers, genital ulcers, papulopustular lesions, nodular lesions or arthritis were included. Where possible, risk ratios were calculated for binary outcomes and mean difference for continuous outcomes., Results: Among the 3927 references that were screened, 37 were included in the analyses. Twenty-seven of these assessed mucocutaneous and 17 assessed joint involvement. Twenty-one of these studies were randomised controlled trials (RCTs). RCTs with colchicine, azathioprine, interferon-alpha, thalidomide, etanercept and apremilast showed beneficial results with some differences according to lesion type and gender. These agents were generally well tolerated with few adverse events causing withdrawal from the study., Conclusions: RCTs comprised more than a half (21/37, 57%) of the sources included in the evidence synthesis related to skin, mucosa and joint involvement applicable for the EULAR Recommendations for the management of BS. Differences in the outcome measures that were used across the included studies often made it difficult to combine and compare the results., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: The faecal calprotectin (FC) test is widely used as a non-invasive method for identifying intestinal inflammation. A recent study suggested FC may help to diagnose gastrointestinal involvement of Behçet's syndrome (GIBS). We aimed to determine whether FC helps to distinguish active from inactive intestinal involvement in GIBS., Methods: We tried to contact 70 GIBS patients registered in our tertiary multidisciplinary clinic. We prospectively collected faecal specimens and serum from 39 GIBS patients who gave informed consent assessing calprotectin and CRP levels followed by a colonoscopy. We included 47 Crohn's disease (CD) patients as controls. Active disease was defined as having ulcer/s on colonoscopy. We filled the Disease Activity Index for Intestinal Behçet's Disease (DAIBD) and Crohn's Disease Activity Index (CDAI). The cut-off for positive FC was defined as ≥150 μg/g., Results: Ulcers were detected in 12/39 GIBS patients. Sensitivity and specificity of the FC test for active disease was 91.7 (95%CI:61.5-99.8) and 74.1% (95%CI:53.7-88.9). Median FC and CRP levels and DAIBD scores were higher among patients with ulcers, whereas serum calprotectin and CDAI scores were not. A negative FC test was the only significant predictor of remission (OR:37.04, 95%CI:2.4-561.6; p=0.009) on multivariate analysis. Among CD patients, 16/25 active patients and 3/22 patients in endoscopic remission had a positive FC test (OR:11, 95%CI:11-49)., Conclusions: FC, but not serum calprotectin seems to be a useful non-invasive tool for assessing disease activity in GIBS. Whether the presence of oral ulcers can cause false positive results remains to be studied.

Several new treatment modalities with different mechanisms of action have been studied in patients with Behçet's syndrome (BS). The aim of the current effort was to update the recommendations in the light of these new data under the auspices of the European League Against Rheumatism (EULAR) Standing Committee for Clinical Affairs. A task force was formed that included BS experts from different specialties including internal medicine, rheumatology, ophthalmology, dermatology, neurology, gastroenterology, oral health medicine and vascular surgery, along with a methodologist, a health professional, two patients and two fellows in charge of the systematic literature search. Research questions were determined using a Delphi approach. EULAR standardised operating procedures was used as the framework. Results of the systematic literature review were presented to the task force during a meeting. The former recommendations were modified or new recommendations were formed after thorough discussions followed by voting. The recommendations on the medical management of mucocutaneous, joint, eye, vascular, neurological and gastrointestinal involvement of BS were modified; five overarching principles and a new recommendation about the surgical management of vascular involvement were added. These updated, evidence-based recommendations are intended to help physicians caring for patients with BS. They also attempt to highlight the shortcomings of the available clinical research with the aim of proposing an agenda for further research priorities., Competing Interests: Competing interests: BB received consultant fees from Santen, AbbVie, Allergan, Xoma and research grants from Novartis and Bayer. ITT received honoraria from Servier, AbbVie and Allergan. GH received research grants from Celgene, honoraria from Pfizer and speaker’s fees from Abbvie, MSD and UCB., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Gastrointestinal involvement is rare in Behçet's syndrome (BS) patients from the Mediterranean basin. We report the demographic and disease characteristics, treatment modalities, and outcome of patients with gastrointestinal involvement in BS (GIBS). We retrospectively reviewed the charts of all BS patients in our BS clinic with a diagnosis of GIBS. Patients were invited to the clinic to assess their outcome. Among 8763 BS patients, we identified 60 with GIBS (M/F: 32/28, mean age at diagnosis: 34 ± 10, mean follow-up: 7.5 ± 4 years), after excluding 22 patients with mimicking symptoms. Six (10%) had juvenile-onset BS. The most common intestinal localization was ileocecal region (36/59, 61%) mainly as big oval ulcer/s. Initial treatment was azathioprine for moderate to severe (n = 37) and 5-ASA for mild cases (n = 16). Anti-TNFs and/or thalidomide provided remission in 12 of 18 (67%) refractory patients. Emergency surgery was required in 22 patients. Nine patients did not receive postoperative immunomodulators and 8 relapsed. Overall, 48 of 60 (80%) patients were in remission (29/48 without treatment) at the time of survey. Three recently treated and 2 refractory patients were still active, 3 had died due to non-GI-related reasons, and 4 were lost to follow-up. Careful evaluation for excluding mimickers is important during the diagnosis of GIBS. Azathioprine seems to be a good choice as first-line treatment with high remission rates and few adverse events. Thalidomide and/or TNF-alpha antagonists may be preferred in resistant cases. Surgery may be required for perforations or massive bleeding, and postoperative immunosuppressive treatment is necessary for preventing postoperative recurrences.

Objectives: A number of patients with Behçet's disease (BD) associated with myelodysplastic syndrome (MDS) with or without trisomy 8 have been reported. A high frequency of gastrointestinal (GI) involvement was reported in such patients. The aim of this systematic literature review was to delineate whether GI involvement is an inherent feature of BD associated with MDS, whether these patients do actually have BD rather than GI symptoms related to MDS, and whether the presence of trisomy 8 plays a role in the disease expression of BD associated with MDS., Methods: A systematic literature review was performed in PubMed using the keywords (Behçet's disease OR Behçet's syndrome) AND (myelodysplastic syndrome OR trisomy 8) until December 2013., Results: Data from 39 manuscripts that met the inclusion criteria, reporting on 52 patients were analysed. GI involvement was common in reports from both the Far East and non-Far East countries (75% vs. 50.0%, p=0.15). These patients had typical BD manifestations, except for 1 patient who had only oral ulcers and gastrointestinal involvement. The presence of trisomy 8 seems to be associated with an increased frequency of fever (79.5% vs. 33.3%, p=0.005)., Conclusions: GI involvement seems to be an inherent feature of BD associated with MDS regardless of geographic differences. Despite the increased frequency of GI involvement in these patients, MDS does not seem to modify the clinical expression of gastrointestinal involvement. Presence of trisomy 8 seems to modify the disease expression with an increased frequency of fever.

We report a patient with Behçet's syndrome who presented with upper gastrointestinal haemorrhage. Gastroduodenoscopy showed a gastroduodenal fistula which caused the appearance of double pylorus in the antrum. The possibility of peptic ulcer disease related to non-steroidal anti-inflammatory drug use or Behçet's syndrome itself, as the cause of this rare condition in this patient is discussed.

Objectives: Gastrointestinal involvement of Behçet's syndrome is usually treated with glucocorticoids, 5-aminosalicylic acid compounds and azathioprine. However, some patients are refractory to these conventional therapy modalities. In this paper we report our experience on 13 patients with gastrointestinal involvement of Behçet's syndrome who were refractory to the conventional therapy and who were treated with TNF-alpha antagonists and/or thalidomide., Methods: We reviewed the charts of our Behçet's syndrome patients with gastrointestinal involvement and identified those who were treated with TNF-alpha antagonists and/or thalidomide. Demographic features, previous and concomitant drugs, previous surgery, time to remission and duration of remission were tabulated. We also performed a systematic review of publications on gastrointestinal involvement of Behçet's syndrome patients treated with TNF-alpha antagonists and/or thalidomide., Results: Among our 64 patients with gastrointestinal involvement of Behçet's syndrome, we identified 13 (20%) (7 women, 6 men, mean age 27.4±9.4) who had been treated with TNF-alpha antagonists and/or thalidomide. Their previous medications were glucocorticoids (13/13), azathioprine (13/13), 5-aminosalicylic acid derivatives (3/13) and budesonide (1/13). Clinical and endoscopic remission was obtained in 10 patients. One patient died with sepsis. The systematic literature search revealed 91 cases who had used TNF-alpha antagonists and 15 who had used thalidomide. Among the patients who had received TNF-alpha antagonists, clinical remission was obtained in 47/91 patients (51%), while endoscopic remission was observed in 21/46 (45%) who had a control colonoscopy., Conclusions: One fifth of our Behçet's syndrome patients with gastrointestinal involvement were refractory to conventional treatment modalities. Remission was obtained with TNF-alpha antagonists and/or thalidomide in about 75% of the cases.

Objective: Antibiotic-associated hemorrhagic colitis is a distinct form of antibiotic-associated bloody diarrhea (AABD) in which Clostridium difficile is absent. Although the cause is not exactly known, reports have suggested the role of Klebsiella oxytoca and/or C. difficile., Materials and Methods: Between 2001 and 2006, stool samples of 21 consecutive patients with AABD were cultured for common enteric pathogens and K. oxytoca, and were tested for the presence of parasites and C. difficile toxin A+B within the first 24 h of their initial admission and a colonoscopy was performed when available. The patients were followed up prospectively by telephone interviews., Results: The occurrence of symptoms ranged between 6 h and 14 days following the first dose of the antibiotic responsible and the duration of the AABD ranged between 6 h and 21 days. The antibiotic responsible was oral ampicillin/sulbactam in 18 (85%) cases. C. difficile toxin A+B production by enzyme-linked immunosorbent assay and K. oxytoca growth in stool cultures were detected in six (29%) and 11 (51%) of 21 patients, respectively. Endoscopic morphology and histology in a limited number of patients revealed no more than a nonspecific inflammation and acute colitis, respectively., Conclusion: This study confirms that antibiotic-associated hemorrhagic colitis, as a distinct entity in relation to K. oxytoca, is seen in half of the patients with AABD. Most of the cases are seen within a week following the antibiotic use. Almost all of the patients did not develop any flares during the long-term antibiotic-free follow-up. In some of the patients with AABD, there was coexistence of K. oxytoca with C. difficile toxin A+B.

Objectives: Takayasu arteritis (TA) may be associated with inflammatory bowel disease (IBD). As there is such an overlap and since both diseases show granulomatous histopathological lesions we reasoned similar biological pathways might be implicated in both conditions. Therefore, we investigated the prevalence of anti-Saccharomyces cerevisiae (ASCA) and anti-neutrophil cytoplasmic (ANCA) antibodies - serological markers for IBD-among patients with TA., Methods: Thirty-two patients with TA, 21 with Crohn's disease (CD), 17 with ulcerative colitis (UC) and 34 healthy controls were studied. Among 32 patients with TA, 2 had CD and one had UC concomitantly. ASCA Ig A and Ig G antibodies were analyzed using a commercial ELISA kit. Immune fluorescence analysis (IFA) was used to assess the presence of ANCA antibodies., Results: Only patients with CD had significantly higher levels of both ASCA Ig A and Ig G, compared to patients with TA and healthy controls. Similarly, the frequency of ASCA positive patients was higher only among patients with CD. ASCA Ig A and Ig G antibodies were found in 16 % (5/32) of patients with TA. Among 3 patients, in whom TA and IBD co-existed, only one (one with CD) had positive ASCA Ig G and A antibodies. The p-ANCA antibodies were present among patients with UC (35 %) and CD (10 %)., Conclusion: ASCA positivity in TA was similar to that found in UC and healthy controls. No ANCA antibodies were detected among patients with TA.

Panayiotopoulos syndrome is a common benign epilepsy affecting otherwise healthy children that present with autonomic seizures, in which nausea, retching, and vomiting are particularly common and prominent. Because of the unusual ictal symptoms and lengthy manifestations, misdiagnosis is a common major problem. We describe a young girl with intractable and lengthy vomiting attacks, several admissions to hospitals, and extensive gastroenterological workup for several years from early childhood. On all previous occasions the diagnosis varied from psychosomatic disease, to functional dyspepsia, to cyclic vomiting syndrome. The possibility of autonomic epileptic seizures and Panayiotopoulos syndrome, though likely, was not considered.

Background and Aim: YKL-40 is secreted by macrophages and neutrophils and is a growth factor for vascular endothelial cells and fibroblasts. Elevated serum levels of YKL-40 have been reported in patients with various inflammatory conditions and ongoing fibrosis. The aim of this study was to investigate the relationship between serum concentrations of YKL-40 and disease activity, acute phase reactants, and the presence of strictures in patients with Crohn's disease (CD)., Methods: We studied the serum concentrations of YKL-40 in 41 patients with CD, in which 12 had an endoscopically- or radiologically-proven stricture formation. Forty-six age- and sex-matched healthy volunteers served as controls and a multivariate regression analysis was performed to find out the independent predictors of intestinal strictures and clinical activity., Results: The serum YKL-40 concentrations in the patients were significantly higher than that in the healthy controls (105.69 +/- 88.08 ng/mL [range 20.23-333.57]vs 44.92 +/- 24.89 ng/mL [range 18.31-113.43], P = 0.000) and patients with a stricture formation had significantly higher YKL-40 levels than those without strictures (167.50 +/- 119.30 ng/mL [range 23.62-333.57]vs 80.12 +/- 56.38 ng/mL [range 20.23-259.19], P = 0.003). Significant correlations were noted between YKL-40 levels and clinical activity (r = 0.681; P = 0.000) and the presence of intestinal strictures (r = 0.457; P = 0.003). The multivariate regression analysis found the serum YKL-40 levels to be an independent predictor of intestinal strictures (P = 0.001) and clinical activity (P = 0.001)., Conclusion: Patients with CD, particularly those with a stricture formation, have significantly higher levels of YKL-40. YKL-40 seems to be a useful marker of disease activity as well as stricture formation in patients with CD.

Objective: Crohn's disease (CD) and ulcerative colitis (UC) share common clinical features with Behçet's syndrome (BS). We surveyed UC and CD patients for pathergy phenomenon and features of BS with the aim of determining how much overlap is present between these 2 entities in a setting where BS is relatively common, the frequency of pathergy positivity in inflammatory bowel disease (IBD) patients and evaluating how International Study Group (ISG) criteria perform in differentiating IBD from BS., Methods: This study was conducted among patients with CD and UC attending the gastroenterology outpatient clinic of a university hospital which is also a referral center for BS. Consecutive CD and UC patients were screened for BS using ISG criteria. Pathergy test was performed and evaluated by 2 independent observers in a masked manner., Results: Ninety-three patients with CD and 130 with UC were surveyed. None of the CD patients fulfilled ISG criteria for BS while 2 of 130 UC patients did. Twenty CD patients had oral ulcers while 4 reported having genital ulcers but no scars could be observed. Twenty-two CD patients had papulopustular lesions, 2 had nodular lesions, 3 had arthritis and none had uveitis. Thirty-two UC patients had oral ulcers, none had genital ulcers, 23 had papulopustular lesions, 3 had nodular lesions, 2 had arthritis and 2 had uveitis. Pathergy test was positive according to at least one of the observers in 10/93 CD and 8/130 UC patients and according to both observers in 4/130 UC patients., Conclusion: Despite similarities between the clinical features of CD and UC with BS, coexistence is uncommon. ISG criteria perform well in differentiating these diseases. About 8% of IBD patients show the pathergy phenomenon.

Stenotrophomonas maltophilia has emerged as an important cause of morbidity and mortality in hospitalized patients. Because trimethoprim-sulfamethoxazole (TMP-SMX) remains the most effective drug for the treatment of S. maltophilia infections, desensitization should be considered in patients with hypersensitivity to TMP-SMX.

This paper describes the first case of common variable immunodeficiency (CVID) and AA amyloidosis. A recently treated tuberculosis, and chronic inflammation induced by frequent respiratory tract infections, were thought to be responsible for the amyloidosis. No other reason for this condition could be detected. Although T cell dysfunction in some CVID patients has been reported, pulmonary tuberculosis is quite rare with this condition. Bacterial or viral agents or evidence in favour of intestinal tuberculosis, which would explain this patient's recurrent diarrhea, were not found. In this case, the response of the attacks of diarrhea to metranidazole and the histologic observation of extensive intestinal amyloid deposition, which is known to decrease intestinal motility, made us conclude that the diarrhea was associated with bacterial overgrowth. In this report, we discuss the association of CVID and tuberculosis to secondary amyloidosis and recurrent diarrhea.

Background and Aim: The present study was designed to identify a cut-off value to define subjective and relatively objective criteria of constipation using the visual scale analog questionnaire (VSAQ) in healthy subjects. In addition, the importance of recall bias when evaluating constipation was investigated by repeating the questionnaire and ensuring the subjects maintained diaries., Methods: Seven hundred and sixty healthy hospital personnel were questioned by means of a standard questionnaire. Subjects were initially asked if they were constipated (self-reported) and their daily defecation frequencies. Severity of the parameters of constipation, the consistency of defecation in the form of hard stools, straining and incomplete evacuation were also investigated using a VSAQ (0-10). Subjects were asked to complete a standard form about their daily bowel habits in the subsequent 7 days (diary). At the end of this series, the questionnaire forms completed at the beginning were readministered. Using the criteria of functional constipation, the prevalence of self-reported, symptom-based (>/=2 criteria) and diary-based (>/=2 criteria in the diary) were defined., Results: Of the subjects, 48.5% (369/760) completed diaries regarding their bowel habits and completed the questionnaire for the second time (198 female, 171 male; mean age 31.6 +/- 7.1 years). According to only interrogation, 29.8% of subjects reported that they were constipated; however, this number increased to 39.6% when symptom-based constipation (>/=2 criteria) was considered. Significant agreement was observed between the results of self-reported constipation in form I and II, and symptom-based and diary-based constipation (concordance = 77.7-98.6%, k = 0.47-0.97). Furthermore, 98.1% of the subjects who reported that they were not constipated scored 3 on the VSAQ; conversely, 91.8% who accepted being constipated scored >3 for the same question. A total of 76.1% subjects who had symptom-based constipation scored 3 on the VSAQ, 97.3% of those who had <2 criteria scored 3. When asked 'Are you constipated?' 1.2% of subjects with none of the criteria for diary-based constipation, and 10.7% of subjects who had one criteria scored >3 on the VSAQ. Also, 91.8% of those with three criteria and 100% of those with four criteria had a score >3 on the VSAQ for the same question., Conclusions: The prevalence of constipation in the questionnaire form based on self-reported, symptom-based and diary-based criteria were highly compatible with the result obtained on readministration. Recall bias was negligibly low. Also, the present results suggest that the diagnosis of constipation is more accurate when >2 criteria are present. In addition, the VSAQ seems to be sensitive enough to differentiate subjects with constipation from those without, when a score of 3 has been chosen as the cut-off value for discrimination. However, this sensitivity was less in the group who stated they were constipated.

Metronidazole and ornidazole, synthetic nitroimidazole derivatives, are used in the treatment of infections caused by anaerobic bacteria and protozoa. The drugs are well tolerated and serious side effects are very rarely encountered. Hepatotoxicity is a rare side effect and hitherto only six cases have been reported. We describe three patients who developed hepatitis after ornidazole use and review the previously reported cases. All three cases used ornidazole in conventional doses and developed hepatitis and associated cholestasis. They improved 1-2 months after discontinuation. We concluded that nitroimidazole derivatives may cause hepatotoxic damage resembling acute cholestatic hepatitis. Early recognition and withdrawal of the drug may prevent further damage.

Objective: In this case-control study, we sought to determine whether the incidence of gallbladder stones (GBS) was increased in chronic renal failure (CRF) patients on a hemodialysis (HD) program. We also evaluated factors, such as lipid profiles and gallbladder motility, that could affect the formation of GBS. In addition, we reviewed other available studies on this subject and compared the factors that might have some influence on the development of GBS., Methods: A total of 182 CRF patients (135 male, 47 female, mean age 32.1 yr) undergoing chronic HD and who were referred to our transplantation center in the last 10 yr and 194 healthy controls (137 male, 57 female, mean age 33.3 yr) were included in the study. Abdominal ultrasound was performed on all patients, and ALT, AST, and lipid profiles were determined. In addition, 19 patients with CRF (12 male, 7 female, mean age 33.5 yr) and 22 controls (14 male, 8 female, mean age 33.2 yr) who were age and sex matched were randomly chosen for gallbladder emptying, monitored by ultrasound at 30-min intervals for 2 h after a mixed meal. Fasting volume, minimal residual volume, and ejection fraction of the gallbladder were assessed. For statistical analysis, chi(2), t test, and logistic regression analysis were used., Results: GBS were detected in seven patients with CRF (3.85%, 5 male, 2 female) and three controls (1.55%, one male, two female) (p > 0.05). The mean follow-up time of CRF patients after diagnosis was 39.3 months (range: 2-168), the mean duration of HD was 21.8 months (range: 1-120). The analysis of seven stones in the CRF group revealed that five were cholesterol-rich stones, and two were mixed (cholesterol and bilirubin) stones. Cholesterol levels were higher in the control group, and triglycerides were higher in the CRF group, but these findings were nonsignificant (p > 0.05). Other biochemical values were not significantly different between the groups. CRF patients with and without GBS were similar in their duration of CRF and HD, age, and other biochemical parameters (p > 0.05). When gallbladder emptying was considered, there was no difference between the two groups in fasting volume, residual volume, and ejection fraction (CRF: 89.7%; controls: 92.3%) of the gallbladders (p > 0.05)., Conclusions: We detected similar incidences of GBS in CRF patients undergoing HD and healthy controls, and this was comparable to the results of most of the previous studies. Young male CRF patients had a nonsignificantly higher incidence of GBS than control males. Although cholesterol-rich GBS were predominant, we could not find any significant difference between the groups when factors that could affect GBS formation, such as lipid profiles and gallbladder motility, were taken into account.

Family history and hepatitis B virus (HBV) infection have been identified as risk factors for hepatocellular carcinoma. We report hepatocellular carcinoma (HCC) diagnosed at the same time in identical twin brothers. Serological analyses of the patients showed that both were chronically infected with HBV. Molecular analyses of the tumor specimens confirmed loss of heterozygocity of the Rb gene region. Both of the patients were unresponsive to chemotherapy and died within the same month with an interval of I wk. With a review of the current literature, we discuss the role of HBV infection and genetic factors on hepatic carcinogenesis.

In this report, we present a patient with chronic hepatitis C-associated cryoglobulinemia who was kept on maintenance interferon treatment because of flare-ups in cryoglobulinemia-associated signs and hepatitis after withdrawal, dose reduction, and increase in dose intervals of interferon. This type of interferon use for treatment of cryoglobulinemia gave us a chance to observe the long-term effects of interferon on cryoglobulinemia and chronic hepatitis C remission for biochemical, virologic, and histologic aspects.

In our clinical experience, postprandial symptomatic hypoglycemic (PSH) patients with H. pylori gastritis showed a substantial improvement in their hypoglycemic symptoms after the eradication of H. pylori. Therefore, in this study we have investigated whether H. pylori gastritis may contribute to the occurrence of PSH. For this purpose, we have evaluated the following parameters in 12 PSH patients with H. pylori gastritis before and one month after the eradication therapy: (1) the number and severity of PSH attacks that occurred in a one-month period using a 30-day diary, (2) the total symptom score following a mixed meal using a visual analog scale questionnaire (VASQ), and (3) the glucose and insulin responses to the mixed meal. After the eradication of H. pylori, the serum insulin responses at 30 and 60 min decreased (P < 0.001 in both), whereas the plasma glucose levels at 150, 180 and 210 min increased significantly (P < 0.001 for 180 min and P < 0.01 in others) following the mixed meal. The number and severity score of PSH attacks that occurred in a one-month period and the area under curve for symptom score in VASQ decreased significantly (P < 0.001 in all). These results suggest that H. pylori gastritis may contribute to the occurrence of PSH.

Tuberculosis may be difficult to diagnose when it presents in an uncommon extrapulmonary site. The authors report a case of splenic tuberculosis mimicking metastatic tumor on computed tomography in a 60-year-old woman who had been treated with combination chemotherapy for nasal angiocentric lymphoma. Diagnostic splenectomy revealed multiple necrotic masses in the spleen, which were consistent with caseating granulomas microscopically. Diagnosis was confirmed by positive cultures in Lowenstein medium, which grew typical Mycobacterium tuberculosis organisms. Following splenectomy, the patient was also treated with a triple-drug antituberculosis regimen with no recurrence of her symptoms.