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Objectives: The long-term consequences of COVID-19 infection on the gastrointestinal tract remain unclear. Here, we aimed to evaluate the prevalence of gastrointestinal symptoms and post-COVID-19 disorders of gut-brain interaction after hospitalisation for SARS-CoV-2 infection. Design: GI-COVID-19 is a prospective, multicentre, controlled study. Patients with and without COVID-19 diagnosis were evaluated on hospital admission and after 1, 6 and 12 months post hospitalisation. Gastrointestinal symptoms, anxiety and depression were assessed using validated questionnaires. Results: The study included 2183 hospitalised patients. The primary analysis included a total of 883 patients (614 patients with COVID-19 and 269 controls) due to the exclusion of patients with pre-existing gastrointestinal symptoms and/or surgery. At enrolment, gastrointestinal symptoms were more frequent among patients with COVID-19 than in the control group (59.3% vs 39.7%, p, Fondazione Cassa di Risparmio in Bologna; Ministero dell’Istruzione, dell’Università e della Ricerca, MIUR; Korean Society of Neurogastroenterology and Mobility, KSNM; Fondazione del Monte di Bologna e Ravenna: H2020, SC1-BHC-01-2019; United European Gastroenterology, UEG; Fondazione Roma, GB’s contribution to this research was partly supported by funding from Fondazione Cassa di Risparmio in Bologna, the Italian Ministry of Education, University and Research; and Fondazione del Monte di Bologna e Ravenna and European Grant H2020, DISCOvERIE, SC1-BHC-01-2019, We thank the European Society of Neurogastroenterology and Motility, the United European Gastroenterology, and the Rome Foundation for supporting this study.

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.

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.

Hepatitis C is one of the leading causes of death in patients with inherited bleeding disorders. Currently, direct-acting antiviral drugs used for the treatment of hepatitis C have become an effective and a reliable option for people with inherited bleeding disorders. The aim of this study is to report the efficacy and safety of ombitasvir + paritaprevir/ritonavir and dasabuvir combination in the treatment of hepatitis C in patients with inherited bleeding disorders.In this retrospective study, we evaluated the efficacy and safety of the combination of ombitasvir + paritaprevir/ritonavir and dasabuvir in 10 adult patients with hemophilia A, 4 patients with hemophilia B, and 1 patient with von Willebrand disease who were infected with hepatitis C genotype 1.Five patients had genotype 1a and 10 patients had genotype 1b chronic hepatitis C. One patient had Child A cirrhosis, 14 patients had chronic hepatitis C without cirrhosis. Hepatitis C virus ribonucleic acid was negative in all patients at week 4 and at the end of the treatment. Sustained virologic response was obtained in all patients. Serious side effects were detected in 3 patients, which were intra- muscular bleeding, erosive gastritis-related gastrointestinal bleeding, and pneumonia.Ombitasvir + paritaprevir combined with ritonavir and dasabuvir ± ribavirin is an effective treatment for patients infected with genotype 1 hepatitis C who have coagulation disorders. Tolerance and side effects are similar to other treatment options.

Coronavirus disease 2019 pandemic was expected to have traumatic effects and increase the anxiety levels of inflamma- tory bowel disease patients.We aimed to investigate the psychosocial effects of the coronavirus disease 2019 pandemic on patients with inflammatory bowel disease by revealing the risk perception for present disease, coping strategies, follow-up characteristics, and treatment adher- ence. This is a cross-sectional, web-based survey study including 798 inflammatory bowel disease patients who were followed at our outpatient clinic and 303 volunteer who did not have any known chronic diseases and were not health professionals were included as the control group.In this study, 281 of the patients were diagnosed with Crohn's disease and 215 with ulcerative colitis. The mean age of patients with Crohn's disease, ulcerative colitis, and the control group were 40.9 ± 13.1, 42.3 ± 12.7, and 39.9 ± 11.6, respectively. Here, 119 (42%) of the Crohn's disease cases, 116 (54%) of the ulcerative colitis cases, and 170 (56%) of the control group were male. Among the 3 groups, coronavirus disease 2019-related post-traumatic stress disorder rates (Impact of Event Scale-Revised33) and State-Trait Anxiety Inventory of current status of anxiety-related anxiety rates were not statistically different while State-Trait Anxiety Inventory of anxiety tendency-related constant anxiety was higher in inflammatory bowel disease patients than the control group (P.017).Inflammatory bowel disease patients with anxiety have a lower quality of life, and this may worsen the clinical course of the disease. Coronavirus disease 2019 is a major source of stress for such a vulnerable population. During the pandemic, psychological support and mental health awareness should be made accessible to all individuals.

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.

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.

Background We investigated associations between baseline use of immunosuppressive drugs and severity of Coronavirus Disease 2019 (COVID-19) in autoimmune hepatitis (AIH). Patients and methods Data of AIH patients with laboratory confirmed COVID-19 were retrospectively collected from 15 countries. The outcomes of AIH patients who were on immunosuppression at the time of COVID-19 were compared to patients who were not on AIH medication. The clinical courses of COVID-19 were classified as (i)-no hospitalization, (ii)-hospitalization without oxygen supplementation, (iii)-hospitalization with oxygen supplementation by nasal cannula or mask, (iv)-intensive care unit (ICU) admission with non-invasive mechanical ventilation, (v)-ICU admission with invasive mechanical ventilation or (vi)-death and analysed using ordinal logistic regression. Results We included 254 AIH patients (79.5%, female) with a median age of 50 (range, 17-85) years. At the onset of COVID-19, 234 patients (92.1%) were on treatment with glucocorticoids (n = 156), thiopurines (n = 151), mycophenolate mofetil (n = 22) or tacrolimus (n = 16), alone or in combinations. Overall, 94 (37%) patients were hospitalized and 18 (7.1%) patients died. Use of systemic glucocorticoids (adjusted odds ratio [aOR] 4.73, 95% CI 1.12-25.89) and thiopurines (aOR 4.78, 95% CI 1.33-23.50) for AIH was associated with worse COVID-19 severity, after adjusting for age-sex, comorbidities and presence of cirrhosis. Baseline treatment with mycophenolate mofetil (aOR 3.56, 95% CI 0.76-20.56) and tacrolimus (aOR 4.09, 95% CI 0.69-27.00) were also associated with more severe COVID-19 courses in a smaller subset of treated patients. Conclusion Baseline treatment with systemic glucocorticoids or thiopurines prior to the onset of COVID-19 was significantly associated with COVID-19 severity in patients with AIH., Italian Ministry of University and Research (MIUR)-Department of Excellence project PREMIA (PREcision MedIcine Approach: bringing biomarker research to clinic), A. Gerussi, L. Cristoferi, and P. Invernizzi acknowledge that this research was partially supported by the Italian Ministry of University and Research (MIUR)-Department of Excellence project PREMIA (PREcision MedIcine Approach: bringing biomarker research to clinic).

Objective In this study, we aimed to investigate the effects of direct antiviral treatment on depression, anxiety, fatigue and quality of life in patients with chronic hepatitis C. Methods Subjects included in study were treatment experienced and treatment naive chronic hepatitis C patients admitted to the hepatology outpatient clinic between December 2016 and June 2017. Before and after the treatment, Beck depression, Beck anxiety, liver-specific quality of life and fatigue severity-impact scales were administered. Descriptive statistical methods, Kolmogorov-Smirnov distribution test Wilcoxon sign and kappa coefficient tests were used to evaluate the study data. Results Forty-four patients were included in the study; however, it was completed with 35 patients only, as some of the patients were excluded for various reasons. There was no significant difference between depression and anxiety scores of the patients before and after the treatment, but depression and anxiety were found to be recovered in 28.5% (4/14) and 23.5% (4/17) of the subjects, respectively. At the end of the treatment, fatigue severity-impact scales and liver-specific quality of life were not significantly different from those before the treatment. Conclusion In this study, we found that direct antivirals did not lead to depression, anxiety or fatigue and did not decrease liver-specific quality of life. In some cases, depression and anxiety decreased after the treatment.

Purpose: Vitamin B12 causes hematologic and neuropsychiatric disorders, so it is important to evaluate it in risky situations. In this study, we aimed to evaluate the association between somatostatin receptor ligands and vitamin B12 levels in patients with acromegaly.Methods: Patients who were followed up with the diagnosis of acromegaly in the Endocrinology and Metabolism outpatient clinic of Istanbul University-Cerrahpaşa Medical Faculty were evaluated. Patients were divided into groups according to their somatostatin receptor ligand use status. The groups were evaluated according to their vitamin B12 levels, demographic data, and biochemical parameters.Results: One hundred fifty-two patients were evaluated. Thirteen patients had vitamin B12 deficiency. The majority (11/13) of patients with vitamin B12 deficiency were patients using somatostatin receptor ligand. In addition, the number of patients with vitamin B12 deficiency who received lanreotide autogel treatment was significantly higher compared with patients who did not use somatostatin receptor ligand (p = 0.011). Vitamin B12 levels were higher in patients who received lanreotide autogel treatment than in patients who did not use somatostatin receptor ligand treatment (p = 0.040). There was a negative correlation between vitamin B12 levels and lanreotide autogel use time, cumulative lanreotide autogel dose.Conclusion: It is important to evaluate the level of vitamin B 12 in the follow-up of patients with acromegaly using somatostatin receptor ligand treatment.

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.

Background: data regarding outcome of Coronavirus disease 2019 (COVID-19) in patients with autoimmune hepatitis (AIH) are lacking. Patients and methods: we performed a retrospective study on AIH patients with COVID-19 from 34 centres in Europe and the Americas. We analyzed factors associated with severe COVID-19 outcomes defined as the need for mechanical ventilation, intensive care admission, and/or death. The outcomes of patients with AIH were compared to a propensity-score matched cohort of non-AIH patients with chronic liver diseases (CLD) and COVID-19. The frequency and clinical significance of new-onset liver injury (alanine aminotransferase>2xupper limit of normal) during COVID-19 was also evaluated. Results: we included 110 AIH patients (80%,female) with a median age of 49 (range:18-85) years at COVID-19 diagnosis. New-onset liver injury was observed in 37.1% (33/89) of the patients. Use of antivirals was associated with liver injury (p=0.041; odds ratio (OR) 3.36[1.05-10.78]) while continued immunosuppression during COVID-19 was associated with a lower rate of liver injury (p=0.009; OR 0.26[0.09-0.71]). The rates of severe COVID-19 (15.5% vs 20.2% p=0.231) and all-cause mortality (10% vs 11.5%; p=0.852) were not different between AIH and non-AIH CLD. Cirrhosis was an independent predictor of severe COVID-19 in patients with AIH (p, Italian Ministry of University; Research (MIUR)-Department of Excellence Project PREMIA; AMAF Monza ONLUS; AIRCS

BackgroundImmunogenicity 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.ObjectiveWe aimed to investigate the prevalence of anti-infliximab (IFX) antibodies in patients with Behçet syndrome together with suitable controls.MethodsWe 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.ResultsAnti-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.ConclusionsImmunogenicity 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.

To evaluate the effects of somatostatin analogs and disease activity status on the upper gastrointestinal system in patients with acromegaly. One hundred eighty-one patients with acromegaly were retrospectively assessed. The demographic, biochemical, pathologic, and radiologic data of the patients were evaluated. The upper gastrointestinal endoscopies and endoscopic biopsies were investigated. We divided patients into four groups according to the use of somatostatin analogs, and into two groups according to disease activity. We compared the data of patients between groups A, B, C, and D, and controlled/uncontrolled groups separately. Before and in the peri-endoscopic period, 67 and 27 patients were being treated with octreotide long-acting release (LAR) (group A) and lanreotide autogel (group B), respectively. Twenty-one patients used somatostatin analogs, but they were stopped for various reasons before upper gastrointestinal endoscopy (group C), and 66 patients did not use a somatostatin analog (group D). In the peri-endoscopic period, 103 (60%) patients were responsive to medical and/or surgical treatment and 67 (40%) patients were non-responsive. The rate of gastritis was higher in group A than in groups B and D. The incidence of duodenitis and gastric ulcer was much higher in group D. The rate of gastritis was higher in the controlled group compared to the uncontrolled group. The study showed that octreotide LAR treatment could be a risk factor in addition to known factors for the development of gastritis in patients with acromegaly.

The meta-analyses of observational studies (OBS) showed the risk of any fracture and hip fracture slightly increased with proton pump inhibitor (PPI) treatment depending on the dose and regardless of time. This was not observed with histamine-2 receptor antagonists (H2RA). The risk of bacterial overgrowth and spontaneous bacterial peritonitis were increased with PPI therapy, but not with H2RA. In meta-analyses of OBS, a slight increase was observed in the risk of community-acquired pneumonia (CAP) in the early stages (1 month) of PPI use and particularly at high doses. In a five-year LOTUS study, no difference was found in vitamin B12, folic acid, vitamin D, and calcium values in terms of the initial and end of follow-up levels. No increase in the risk of premalignant gastric lesions was observed in the meta-analysis of RCTs in which PPI treatment (≥6 months) was given to Helicobacter pylori negative patients. The risk of hypomagnesemia with PPI use was increased in patients having GFR60, using diuretics, and over 65 years of age. Quasi-experimental studies showed a reduced zinc absorption with PPI use. In the meta-analysis of OBS, long-term (1 year) PPI use increased the risk of fundic polyps, but no risk was found in shorter use. The meta-analyses of RCTS showed no difference between PPI and surgery or placebo arms and between the arms of H2RA and placebo in terms of all side effects. No difference was found between the PPI and H2RA arms both in all and serious adverse effects.

Behcet's syndrome (BS) is a multisystem vasculitis that presents with a variety of mucocutaneous manifestations such as oral and genital ulcers, papulopustular lesions and erythema nodosum as well as ocular, vascular, gastrointestinal and nervous system involvement. Although it occurs worldwide, it is especially prevalent in the Far East and around the Mediterranean Sea. Male gender and younger age at disease onset are associated with a more severe disease course. The management of BS depends on the severity of symptoms. If untreated, morbidity and mortality are considerably high in patients with major organ involvement. Multidisciplinary patient care is essential for the management of BS, as it is for other multisystem diseases. Rheumatologists, dermatologists, ophthalmologists, neurologists, cardiovascular surgeons and gastroenterologists are members of the multidisciplinary team. In this study, we reviewed the epidemiology, etiology, diagnostic criteria sets, clinical findings and treatment of BS and highlighted the importance of the multidisciplinary team in the management of BS.

WOS:000535263200001 PubMed ID: 32412898 Aims: This study aimed to determine the predictors of endoscopic recurrence in a cohort of patients with Crohn's disease (CD) with prior intestinal resections. Materials and Methods: The charts of the patients with CD were reviewed in a retrospective manner. Eighty-three patients were eligible for the final analysis. Demographic features of these patients and time between resection and colonoscopy, presence of any macroscopic residual disease in the remnant intestine, and postoperative medications were noted. Rutgeerts score was used to define postoperative endoscopic recurrence. Results: The patients' mean age +/- SD at their final colonoscopy was 42.81 +/- 11.99 yr; and 37 of 83 patients (45%) were female. The mean follow-up time between resection and the final colonoscopy was 51.16 +/- 51.08 months. A total of 51 of 83 patients (61%) were in endoscopic remission (i0, i1); whereas 32 (39%) had an endoscopic recurrence (i2, i3, i4). History of multiple resections (X-2=6.12; p=0.013) and the presence of any postoperative residual disease in the remnant intestine (X-2=5.86; p=0.015) were risk factors; whereas the regular use of azathioprine (AZA) was significantly more common among patients without recurrence (X-2=4.515; p=0.034). In an age-sex adjusted Cox regression analysis history of multiple resections, presence of any postoperative residual disease proved to be independent risk factor for endoscopic recurrence, whereas the regular use of AZA proved to be ineffective. Conclusion: In a retrospective long-term follow-up cohort of resected patients with CD, having multiple resections for CD and the presence of any residual synchronous disease after ileocolonic resection were identified as risk factors for endoscopic recurrence; the latter was never reported in previous studies.

Vasculitic as well as inflammatory characteristics of gastrointestinal Behcet syndrome (GIBS) make it a distinct pattern of bowel inflammation and a bridging disease between vasculitis and inflammatory bowel disease (IBD). Reports indicate that the prevalence of gastrointestinal involvement of Behcet syndrome (BS) shows geographic variation. Since no true population surveys are available, at least some of this variation could be due to selection bias. The usually reported prevalence is less than 1% among patients from Western countries and the Middle East, while this frequency becomes 10% or even higher in the Far East. As in Crohn’s disease (CD), GIBS is seen most commonly in the ileocecal area. Lesions in the esophagus and stomach are distinctly rare. Although endoscopic morphology and distribution pattern of GI ulcerations may help in differentiation between CD and GIBS, it is sometimes difficult to differentiate GIBS from CD unless other stigmata of either condition are present. Among the mucocutaneous signs of BS, genital ulcer is a fairly specific sign of BS; however, unless clearly figured out from the patients’ history, existence of genital ulcers in a short period of time makes its sensitivity very poor. Thus far, complications like perforation and bleeding are more common in GIBS (25–50%) than in CD (∼2%). Management of GIBS is very similar to CD and is based on extrapolation from the IBD experience. As in IBD anti-TNF agents are now being used for refractory cases. This suggests that rather than the differentiation, prediction of complications may be more vital in IBD and BS clinics. Surgical treatment is reserved for complications like perforation, bleeding, obstruction, and stubborn fistula formation. Since relapses are more frequent without medical treatment, partly because of the pathergy phenomenon, surgical resection should be conservative and be applied with optimal postoperative medical treatment.

Data on the prevalence of fecal incontinence in elderly patients admitted to outpatient clinics in Turkey are scarce. The aim of this study was to assess the prevalence of fecal incontinence and the associated risk factors in the elderly outpatients. Patients 60 years and older admitted to a geriatrics outpatient clinic between October 2013 and March 2014 were included. Demographic characteristics, anthropometric measurements, marital status, educational status, parity (for females), fecal incontinence (FI), urinary incontinence (UI), constipation, comorbid conditions, and medications were recorded. FI assessment was based on the Fecal Incontinence Severity Index (FISI). A total of 364 patients (64.8% female, n = 236) with a mean age of 73.2 ± 8.1 years were enrolled in the study. The prevalence of FI was 9.9% (10.2% female, 9.4% male). UI was 42.6%. Co-occurrence of FI and UI was 7.4%. According to the FISI, the most frequent type of defecation was liquid stool (61.1%). While the predictive factors for FI were polypharmacy (standardized coefficient, [r] = 0.203, 95% confidence interval [CI] = 0.009–0.040, p = 0.002), UI (r = 0.134, 95% CI = 0.006–0.156, p = 0.035), and being married (r = 0.200, 95% CI = −0.088 to −0.020, p = 0.002) in females, those were UI (r = 0.306, 95% CI = 0.093–0.309, p

Purpose of review Gastrointestinal system can be involved in primary and secondary vasculitides. The recent data regarding the pathophysiology, clinical findings, diagnosis, management, and outcome of gastrointestinal involvement in different types of vasculitis are reviewed. Recent findings Diagnosis of gastrointestinal vasculitis may be difficult and relies mostly on imaging, because biopsy samples are hard to obtain and superficial mucosal biopsies have a low yield. There are conflicting reports on the association of antineutrophilic cytoplasmic antibodies (ANCA) type with the frequency of gastrointestinal involvement in ANCA-associated vasculitis. Pancreatitis is a rare but serious complication of ANCA-associated vasculitis. Terminal ileitis may be observed in immunoglobulin A vasculitis and can be hard to distinguish from Crohn's disease. High fecal calprotectin levels can indicate active gastrointestinal involvement in both immunoglobulin A vasculitis and Behcet's syndrome. Refractory gastrointestinal involvement in Behcet's syndrome can be treated with thalidomide and/or TNF-α antagonists. The outcome of mesenteric vasculitis in systemic lupus erythematosus can be improved with high-dose glucocorticoids and cyclophosphamide or rituximab. Summary Gastrointestinal system can be commonly involved in immunoglobulin A vasculitis, ANCA-associated vasculitis, polyarteritis nodosa, and Behcet's syndrome and can be an important cause of morbidity and mortality. Treatment depends on the type of vasculitis and is usually with high-dose corticosteroids and immunosuppressives.

Hatemi, Ali Ibrahim/0000-0002-8385-9253; WOS:000474444300003 PubMed ID: 31290746 Background/Aims: The aim of the present study was to compare the demographic features and long-term outcomes of patients with inflammatory bowel disease (IBD) with or without ankylosing spondylitis (AS). Materials and Methods: Among 1640 IBD (Crohn's disease and ulcerative colitis), 76 patients with IBD+AS were identified. The study group consisted of 76 patients with IBD with synchronous AS. The control group consisted of patients with only IBD, and those were selected according to their registry sequence number being the previous and next case to the diseased case with IBD+AS. The primary endpoint was to compare the rate of intestinal resections between both groups (IBD vs. IBD+AS). Results: Among 76 patients with IBD+AS, 52 (68%) first presented with IBD, 11 (15%) with AS, and the remaining 13 (17%) had both diagnoses at the same time. The mean follow-up time was significantly longer in patients with IBD+AS (43.4 vs. 27.8 months; p=0.01). Twenty-two percent of patients with IBD and 14% of those with IBD+AS had an intestinal resection (p=NS). Biologic and systemic corticosteroid treatments were significantly more common among patients with IBD+AS (32% vs. 7% for biologics, p

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.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.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).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.

Background Immunogenicity of anti-TNFs has been recognised as an important problem that may cause loss of efficacy and adverse events such as infusion reactions. Anti-TNFs are being increasingly used among patients with Behcet’s syndrome (BS). Objectives We aimed to investigate the prevalence of anti-drug antibodies against infliximab (IFX) in patients with BS together with controls. Methods We collected serum samples from 66 consecutive BS patients (51 M, 15 F and mean age 37±9 years) who were treated with IFX. IFX was used for eye involvement in 43, vascular involvement in 12, nervous system involvement in 8 and arthritis in 2 patients. Additionally, 53 ankylosing spondylitis (AS), 25 Crohn’s disease (CD) and 27 rheumatoid arthritis (RA) patients, and 31 healthy subjects were included as controls. We included patients who had received at least 4 cycles of IFX. Samples were collected just before an infusion, stored at −80o C until analysis, and serum IFX trough levels and anti-IFX antibodies were measured by ELISA at the same time. We used a cut-off value of 1 µg/mL for serum IFX trough level, extrapolating from RA studies. After serum sampling, we continued to follow up patients. Results Anti-IFX antibodies were detected in 4 (6%) BS, 5 (18.5%) RA, 3 (12%) CD, and 1 (%2) AS patient, and in none of the healthy subjects. The mean number of IFX cycles was 19±14 in BS, 21±13 in RA, 19±21 in CD, and 33±18 in AS patients. Allergic reactions had occurred in 9 (14%) BS, 6 (22%) RA, 5 (20%) CD, and 4 (7.5%) AS patients. 3/6 RA patients and 3/5 CD patients who had experienced an allergic reaction had anti-IFX antibodies whereas none of BS and AS patients did. 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 patients with anti-IFX antibodies and in 25/158 without anti-IFX antibodies (46% vs 16%; p=0.015). We were able to get samples before at least 2 consecutive infusions in 27 BS patients and the presence of anti-IFX antibodies was consistent across the samples in all of these patients. We were able to get samples before the infusion and at week 2 in 5 BS patients. Serum IFX level was below 1 µg/mL before IFX and above 1 µg/mL at week 2 in all of these 5 patients. During a median follow up of 1.5 years, 2/4 BS patients with anti-IFX antibodies had flares. Among the 62 patients without anti-IFX antibodies, 49 are still on IFX and IFX was stopped due to remission in 12 and due to infusion reaction in one patient. Overall, 5 infusion reactions occurred during the follow up (4 without anti-IFX antibodies and 1 with anti-IFX antibodies; 6.5% vs 25%). Conclusions Immunogenicity does not seem to be an important problem in BS patients treated with IFX. The frequency of anti-IFX antibodies was lower than RA and CD patients. This might be related to concomitant immunosuppressive and corticosteroid use among BS patients. The presence of anti-IFX antibodies may not be associated with efficacy loss in BS. However, longer follow-up is needed to make that statement as BS has a relapsing-remitting course. Disclosure of Interest None declared

Non-alcoholic fatty liver disease (NAFLD) is associated with insulin resistance (IR). We evaluated whether IR contributes to hepatocyte apoptosis, inflammation, and fibrosis in NAFLD.Forty-four teetotaller patients with biopsy-proven diagnosis of NAFLD were enrolled. Twenty-eight NAFLD patients with IR were compared with 16 subjects without IR. For apoptotic activity caspase 3 and 8, transcription nuclear factor kB (NF-kB), and anti-apoptotic Bcl-2 protein were determined through immunohistochemical methods.HOMA-IR index was significantly correlated with the stage and caspase 3- and 8 levels (p= 0.001, 0.02, and 0.01, respectively). HOMA-IR index was independently associated with the severity of fibrosis ( = 5.9, p = 0.001), caspase-3 ( = 0.16, p = 0.001), and caspase-8 (b =0.032, p = 0.018) levels. TNF-sRp55 level was positively correlated with HOMA-IR index (p = 0.024). Patients with IR had significantly higher necroinflammatory grade, stage, caspase-3, and caspase-8 levels than those without IR (p = 0.022, 0.007, 0.031, and p = 0.011, respectively). HOMA-IR index had statistically significant values for distinguishing of severe necroinflammatory grade, stage and for differentiating NASH from simple fatty liver (AUC = 0.78, 0.76, and 0.82, respectively).This study demonstrates that IR in NAFLD is associated with enhanced hepatocyte apoptosis and histopathologic disease severity. These data indicate that NAFLD patients with IR may have increased risk for disease progression.

Behcet disease (BD) is a variable vessel vasculitis that can involve several organs and systems. Gastrointestinal (GI) involvement has an acute exacerbating course with ulcers, most commonly in the ileocolonic area. These ulcers can be large and deep, causing perforation and massive bleeding. This article highlights the current knowledge on the epidemiology, clinical findings, diagnosis, and management of GI involvement of BD, with emphasis on recent findings.

Behçet’s syndrome (BS) is a multisystem vasculitis that presents with a variety of mucocutaneous manifestations such as oral and genital ulcers, papulopustular lesions and erythema nodosum as well as ocular, vascular, gastrointestinal and nervous system involvement. Although it occurs worldwide, it is especially prevalent in the Far East and around the Mediterranean Sea. Male gender and younger age at disease onset are associated with a more severe disease course. The management of BS depends on the severity of symptoms. If untreated, morbidity and mortality are considerably high in patients with major organ involvement. Multidisciplinary patient care is essential for the management of BS, as it is for other multisystem diseases. Rheumatologists, dermatologists, ophthalmologists, neurologists, cardiovascular surgeons and gastroenterologists are members of the multidisciplinary team. In this study, we reviewed the epidemiology, etiology, diagnostic criteria sets, clinical findings and treatment of BS and highlighted the importance of the multidisciplinary team in the management of BS.

Background Although faecal calprotectin can predict mucosal remission in ulcerative colitis, the CRP level in this context is insufficient and frequently stay under the current cut off level. While some patients with active mucosal disease have normal CRP levels most patients in mucosal remission have much lower CRP levels. The aim of this study is to define CRP cut off levels in the prediction of mucosal remission, considering both extensiveness and severity, in ulcerative colitis. Methods We retrospectively reviewed colonoscopy reports of ulcerative colitis patients (who are not on any steroid treatment at that time) which were performed between December 2016 and March 2019 and also their CRP levels which were obtained at the same week of the colonoscopy examination. We excluded the data of patients with any other possible cause of inflammation or infection at the time of laboratory assessment. Degree of mucosal disease at colonoscopy was evaluated according to endoscopic Mayo score. Mucosal remission was defined as endoscopic Mayo score 0 or 1. The extent of mucosal inflammation was classified according to Montreal classification. The CRP level with optimal sensitivity and specificity for mucosal remission prediction was assessed by ROC curve analysis and positive and negative predictive values were also calculated. Results A total of 331 colonoscopy reports of 260 patients (122 m, 138 f) were involved in this study. There were no significant differences between ages of patients when compared with ex, and Montreal classification and we did not find any correlation between age and CRP levels. Sensitivity, specificity, positive predictive value and negative predictive values for 5 mg/l, 3 mg /l and 2 mg/l are summarised in Table 1. CRP levels which predict Mayo 0 disease, mucosal remission (Mayo 0–1) and Mayo 3 disease are shown in Table 2. At the ROC curve analysis, we found that CRP level of approximately 2.9 mg/l can predict mucosal remission with a 77% sensitivity and % 80 specificity in all examinations without grouping into a separate segmental disease. For subgroups with Montreal E1, E2 and E3 ROC curve analysis suggested 1,8 mg/l (sn. 84%, sp. 90%), 2,7 mg/l (sn. 75%, sp. 75%) and 3 mg/l (sn. 80%, sp. 80%) CRP levels can be used for prediction of mucosal remission respectively (Table 3). It is important to emphasise that 30% of all patients with Mayo 3 colonoscopy and further 23% of patients with Montreal E3–Mayo 3 activity have CRP levels below the regular cut-off value of 5 mg/l. Conclusion CRP cut-off level of approximately 2.9 mg/l can predict mucosal remission in ulcerative colitis better than standard cut-off of 5 mg/l which has a low positive predictive value and specificity even at extended and active mucosal disease.

Background/Aims: To provide a new mathematical formula to predict liver fibrosis in patients with chronic viral hepatitis. Materials and Methods: Patients with chronic hepatitis B and C who underwent liver biopsy at different centers were included in this study. Chronic hepatitis B was defined as immunopositivity for the hepatitis B surface antigen for at least 6 months, and chronic hepatitis C was defined as positivity for HCV RNA for at least 3 months. The histo logical features were evaluated by the histological activity index and fibrosis. Results: In total, 1299 patients were included in the study. The distribution and the mean of the parameters of the patients were as follows: 1009 patients with chronic hepatitis B with a mean age of 45±13/years [emale/male (F/M)=47.5/52.5%] and 290 patients with hepatitis C with a mean age of 52±10.3/years [F/M=61/39%]. When the cut-off value of the REAL TEST formula“[(age x pT x AST)/(PLT/1000)]/100” in patients with hepatitis B was deter mined to be ≥1.37, it was found that it could predict fibrosis with 79% specificity, 78% sensitivity, 85% negative predictive value (NPV), and 70% positive predictive value (PPV) (area under the curve (AUC)=0.852, 95% CI:0.820.87). When the cut-off value of the REAL TEST formula in patients with hepatitis C was determined to be ≥1.99, it was found that it could predict significant fibrosis with 87% specificity, 90% sensitivity, 94.4% NPV, and 79.4% PPV (AUC:0.95, 95% CI:0.93-0.98) Conclusion: The REAL TEST formula results correlated with the pathological findings and may be a useful method for the evaluation of patients with chronic hepatitis B and C.

Hypertriglyceridemia induces acute recurrent pancreatitis, but its role in the etiology of chronic pancreatitis (CP) is controversial. This study aimed to evaluate the clinical, laboratory and radiological findings of 7 patients with CP due to type 1 hyperlipidemia compared to CP patients with other or undefined etiological factors.We retrospectively analyzed the clinical, laboratory and radiological findings of 7 CP patients with type 1 hyperlipidemia compared to CP patients without hypertriglyceridemia. These 7 patients had multiple episodes of acute pancreatitis and had features of CP on abdominal CT, endoscopic retrograde cholangiopancreatography and/or endoscopic ultrasonography.All CP patients were classified into two groups: a group with type 1 hyperlipidemia (n=7) and a group with other etiologies (n=58). The mean triglyceride level was 2323+/-894 mg/dL in the first group. Age at the diagnosis of CP in the first group was significantly younger than that in the second group (16.5+/-5.9 vs 48.3+/-13.5, P0.001). The number of episodes of acute pancreatitis in the first group was significantly higher than that in the second group (15.0+/-6.8 vs 4.0+/-4.6, P=0.011). The number of splenic vein thrombosis in the first group was significantly higher than that in the second group (4/7 vs 9/58, P=0.025). Logistic regression analysis found that younger age was an independent predictor of CP due to hypertriglyceridemia (r=0.418, P=0.000).Type 1 hyperlipidemia appears to be an etiological factor even for a minority of patients with CP. It manifests at a younger age, and the course of the disease might be severe.

Background/Aims In this study we aimed to determine the rate of concordance of endoscopic ultrasonography (EUS)-guided fine needle aspiration (FNA) diagnosis with the final diagnosis obtained by surgery or endoscopic resection and follow-up in upper gastrointestinal subepithelial lesions. Methods We retrospectively studied patients with subepithelial lesions who underwent EUS at our center from 2007 to 2011. Results We had a final diagnosis in 67 patients (mean age±SD, 51.23±12.48 years; 23 [34.3%] female, 44 [65.6%] male). EUS-FNA was performed in all of the patients. On-site pathology was not performed. In nine of the patients, the obtained material which was obtained was insufficient. The cytologic examination was benign in 31 and malignant in 27 of the patients. Based on the final diagnosis, the EUS-FNA had a sensitivity of 96%, a specificity of 100%, and a diagnostic yield of 85%. Conclusions The diagnostic yield of EUS-FNA, in the absence of the on-site cytopathologist, is feasible for the diagnosis of subepithelial lesions of the upper gastrointestinal system.

Background/aims Oxidative stress and insulin resistance (IR) are major contributors in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). The purpose of this study was to find the relation between oxidative stress parameters and histopathological findings in NAFLD patients with and without insulin resistance (IR). Materials and methods Thirty-two patients with no alcohol intake and biopsy-proven diagnosis of NAFLD were studied (M/F: 17/15; mean age 46.5±11.4 years). Twenty-one NAFLD patients with IR were compared with 11 patients without IR. The fasting insulin level was measured, and the insulin resistance index was calculated using the homeostasis model assessment (HOMA) method. Malondialdehyde (MDA) and superoxide dismutase (SOD) activities were measured in tissue and serum specimens. Glutathione (GH) was measured in tissue homogenates. Nitric oxide (NO), vitamin E and C levels were measured in serum. Results Patients with IR had significantly higher tissue MDA levels (p=0.001) and significantly decreased tissue SOD and GH levels (p=0.001 and 0.002, respectively) than those without IR. The steatosis grade, necroinflammatory grade and stage were significantly higher in patients with IR (p=0.035, 0.003 and 0.001, respectively). HOMA IR significantly correlated with the necroinflammatory grade, stage, tissue MDA, SOD and GH (p=0.013, 0.001, 0.008, 0.001 and 0.001, respectively). Serum MDA (β=1.88, p=0.002), serum SOD (β=0.57, p=0.006), tissue MDA (β=0.22, p=0.006), tissue SOD (β=1.48, p=0.071) and stage (β=2.81, p=0.003) were independently associated with increased HOMA IR. Increased MDA [OR: 1.51; 95% CI: (1.03-2.22); p=0.034] was a risk factor for non-alcoholic steatohepatitis (NASH), and increased SOD activity had a preventive effect against NASH [OR: 0.008; 95% CI: (0.001-0.98); p=0.04]. Conclusion This study shows that insulin resistance in NAFLD correlates with enhanced oxidative stress. Histopathological disease severity significantly correlated with oxidative stress parameters. These data show that NAFLD patients with IR may have increased risk for disease progression.

Background/Aims: There are no clinical data available about chronic pancreatitis (CP) on a series of patients of sufficient number in Turkey. In this study, the etiology and clinical features of CP were evaluated in one center, which is a tertiary referral hospital. Materials and Methods: The files of 168 patients who had been diagnosed with CP in our Medical Faculty be tween October 2007 and May 2013 were retrospectively analyzed. The etiological factors, symptoms, complications, and treatment methods were analyzed. Results: The most common etiological factor was alcohol abuse (39%). The average age±SD was 46±15.2 years, and the male:female ratio was 4.2:1 (it was 2.6:1 for other etiologies except alcohol abuse and 15.5:1 in alcoholic CP patients, p

BACKGROUND/AIMS Several guidelines recommend the use of tenofovir or entecavir as the first-line treatment for hepatitis B due to the lower resistance rates of these drugs than lamivudine, although lamivudine may still be preferred because of its low adverse effect profile and cost. It is important to know which patients might benefit from lamivudine as the first-line treatment. We aimed to assess the success rates of lamivudine, entecavir, and tenofovir, as well as the resistance rates, frequencies of HBsAg clearance, and risk factors for lamivudine resistance. MATERIALS AND METHODS A total of 191 patients with chronic HBeAg-negative hepatitis who were treated with lamivudine, entecavir, or tenofovir were included. Predictors of resistance to lamivudine were analyzed. RESULTS The cumulative first-, second-, third-, fourth-, and fifth-year rates of virologic breakthrough during extended lamivudine therapy were 24%, 30%, 38%, 46%, and 54%, respectively. The rate of undetectable DNA at the 60th month of those who took lamivudine was 51%. Cox regression analysis revealed that positive HBV DNA at the sixth month (HR=15; 95% CI: [7.1-33], p=0.001), being aged 41 years or more (HR=3.4; 95% CI: [1.8-6.4], p=0.001), and baseline HBV DNA of 170,500 IU/mL or higher (HR=2.1; 95% CI: [1.2-3.7], p=0.01) were independently associated with the development of resistance to lamivudine. CONCLUSION In HBeAg-negative chronic hepatitis B, baseline serum hepatitis B virus DNA levels exceeding 170,500 IU/mL, partial virologic response in the sixth month, and age of 41 years or more were independent predictors for virologic breakthrough. Moreover, 2% of these patients cleared HBsAg.

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.