[Indications, diagnoses and quality markers in upper and lower endoscopies in 2010 and 2011 at the 1st Department of Medicine, Semmelweis University, Budapest]. / A felso és alsó endoszkópiák indikációja, a diagnózisok megoszlása és minoségi mutatók 2010­2011-ben a Semmelweis Egyetem I. Belgyógyászati Klinikáján.

INTRODUCTION AND AIM: The aim was to assess the incidence of endoscopic findings based on the indication of the procedures in upper/lower endoscopies, and measuring quality indicators of colonoscopies at the 1st Department of Medicine, Semmelweis University, Budapest. METHOD: Data of 2987 patients (male/female:1361/1626, mean age: 60.7 years(y), SD: 16.7y) between 01.01.2010 and 31.12.2011 were analyzed. Both inpatient and outpatient records were collected. RESULTS: Incidence of peptic ulcer disease, esophageal varices, gastric polyps and gastric cancer were 10.8%, 4.5%, 6.1%, 2.9% in upper endoscopies, respectively. In colonoscopies colorectal polyps, diverticulosis, colorectal cancer and IBD were found in 29.9%, 22.4%, 6.9%, 9.7%, respectively. In patients having upper endoscopy with GI bleeding indication, older age (p<0.001), male gender (p<0.001, OR: 1.64), acenocoumarol/heparin use (p<0,001, peptic ulcers and esophageal varices were more frequent (p<0.001, OR: 2.83 and p<0.001, OR: 2.79), while in colonoscopies colorectal cancer had higher incidence (p<0.001, OR:3.27). 81% of colonoscopies were complete. Causes of incomplete procedures were ineffective bowel preparation (38.2%), technical difficulties (25.1%) and strictures (20.5%). CONCLUSION: The endoscopic findings and quality indicators (adenoma detection rate, coecal intubation rate) were in line with that reported in published series. Orv. Hetil., 2016, 157(52), 2074-2081.

Has there been a change in the natural history of Crohn's disease? Surgical rates and medical management in a population-based inception cohort from Western Hungary between 1977-2009.

OBJECTIVES: Medical therapy for Crohn's disease (CD) has changed significantly over the past 20 years with increasing use of immunosuppressives. In contrast, surgery rates are still high and there is little evidence that disease outcomes for CD have changed over the past decades. The objective of this study was to analyze the evolution of the surgical rates and medical therapy in the population-based Veszprem province database. METHODS: Data of 506 incident CD patients were analyzed (age at diagnosis: 31.5 years, s.d. 13.8 years). Both hospital and outpatient records were collected and comprehensively reviewed. The study population was divided into three groups by the year of diagnosis (cohort A: 1977-1989, cohort B: 1990-1998 and cohort C: 1999-2008). RESULTS: Overall, azathioprine (AZA), systemic steroid, and biological (only available after 1998) exposure was 45.8, 68.6, and 9.5%, respectively. The 1- and 5-year probability of AZA use were 3.2 and 6.2% in cohort A, 11.4 and 29.9% in cohort B, and 34.8 and 46.2% in cohort C. In a multivariate Cox-regression analysis, decade of diagnosis (P < 0.001, hazard ratio (HR)(cohorts B-C): 2.88-6.53), age at onset (P = 0.008, HR: 1.76), disease behavior at diagnosis (P < 0.001, HR(complicated): 1.76-2.07), and need for systemic steroids (P < 0.001, HR: 2.71) were significantly associated with the time to initiation of AZA therapy. Early AZA use was significantly associated with the time to intestinal surgery in CD patients; in a multivariate Cox analysis (HR: 0.43, 95% confidence interval (CI): 0.28-0.65) and after matching on propensity scores for AZA use (HR: 0.42, 95% CI: 0.26-0.67). CONCLUSIONS: This population-based inception cohort has shown that the recent reduction in surgical rates was independently associated with increased and earlier AZA use.

Treatment of extraintestinal manifestations in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a systemic disease associated with a large number of extraintestinal manifestations (EIM). EIM are present in 15-20% of patients with ulcerative colitis and in 20-40% of patients with Crohn's disease. The management of EIM is best provided by a multidisciplinary team, which includes specialists in the affected organ systems with training in the treatment of IBD. Therapeutic strategy is often empirical. This is explained by the paucity of randomized-controlled studies for the specific treatment of EIM in IBD and by the fact that treatment models are based on extrapolation from patients with similar conditions but without IBD. For most EIM, the mainstay of therapy is the treatment of the underlying active IBD. However, some EIM such as axial arthritis, pyoderma gangrenosum, uveitis and primary sclerosing cholangitis run a clinical course independent of IBD activity and need specific therapy (e.g. TNF antagonists in ankylosing spondylitis and skin manifestations). This review summarizes the conventional and novel (e.g. anti-TNF) treatment modalities, and the therapeutic implications for the management of extraintestinal symptoms in IBD, in order to assist clinicians in optimizing treatment strategies for IBD patients with EIM.

[The effect of early immunosuppressive therapy on the rate of resections performed in patients with Chron's disease, in Veszprém county, Hungary, a population-based cohort study]. / A korai immunszuppresszív kezelés hatása a reszekciós mutétek arányára Crohn-betegekben, Veszprém megyében, populációs alapú kohorszvizsgálat alapján.

UNLABELLED: Medical therapy for Crohn's disease has changed significantly over the past 20 years with the increasing use of immunosuppressants. In contrast, surgery rates are still high and evidence about the the changes in the outcome of Crohn's disease over the past decades is scarce. AIMS: The objective of this study was to analyze the evolution of the surgical rates and medical therapy in the population-based Veszprém county database. METHODS: Data of 506 Crohn's disease patients were analyzed (age at diagnosis: 31.5 years, SD: 13.8 years). Both hospital and outpatient records were collected and comprehensively reviewed. The study population was divided into three groups based on the year of diagnosis (cohort A: 1977-1989, cohort B: 1990-1998 and cohort C: 1999-2008). RESULTS: Overall azathioprine, systemic steroid, and biological (only available after 1998) exposure was 45.8, 68.6, and 9.5%, respectively. The 1 and 5-year probabilities of azathioprine use were 3.2 and 6.2% in cohort A, 11.4 and 29.9% in cohort B, and 34.8 and 46.2% in cohort C. In multivariate analysis, decade of diagnosis (P<0.001), age at onset (P = 0.008), disease behavior at diagnosis (P<0.001), and need for systemic steroids (P<0.001) were significantly associated with the time to initiation of azathioprine therapy. Early azathioprine use was significantly associated with the time to intestinal surgery in Crohn's disease patients; in a multivariate Cox analysis (HR: 0.43, 95% confidence interval (CI): 0.28-0.65) and after matching on propensity scores for azathioprine use (HR: 0.42,95% CI:0.26-0.67). CONCLUSIONS: This population-based inception cohort showed that reduction in surgical rates was independently associated with increased and earlier azathioprine use.

Nutritional influences in selected gastrointestinal diseases.

Nutritional factors, as sources of luminal antigens, have been thought to be important factors in the immunopathogenesis of numerous gastrointestinal diseases. In some diseases, the role of the nutritional component is causal in the susceptible host. Such diseases include celiac disease, a common heritable chronic inflammatory condition of the small intestine induced by dietary wheat, rye and barley, in susceptible individuals. Specific HLA-DQ2 and HLA-DQ8 risk alleles are necessary, but not sufficient, for disease development. The well-defined role of HLA-DQ heterodimers encoded by these alleles is to present cereal peptides to CD4+ T cells, activating an inflammatory immune response in the intestine. Genome-wide association studies have been performed which identified the IL2-IL21 risk locus and other genes with immune functions and key roles in thymic T-cell selection. Another example for this group is Wilson's disease, an autosomal recessive disorder of copper metabolism caused by mutation of the ATP7B gene, resulting in a defect of biliary copper excretion and toxic accumulation in the body, especially in the liver, brain and cornea, resulting in hepatic and/or neurological symptoms. In other diseases, however, the association is less well established. In such endeavor, epidemiological observations may become a valuable part of the overall investigations aimed at identifying dietary factors, which are involved in the initiation and perpetuation of the specific disease. As an example, relationships between nutrition and colorectal cancer have been hypothesized early on (e.g. folate, calcium, vitamin D, red meat). Similarly, intake of certain diet constituents like fat, refined sugar, fruits, vegetables and fiber was reported to be associated with the expression of inflammatory bowel diseases. In addition, in children with active Crohn's disease, enteral nutrition was found to be equally effective as corticosteroids in induction of remission, with mucosal healing induced by downregulation of mucosal pro-inflammatory cytokine profiles in both the ileum and the colon after enteral nutrition. However, the particular effect of the consumption of each type of food remains questionable in most cases, at least in part because of insufficient data and serious methodological limitations (e.g. recall bias, heterogeneity between collected data, lack of correction for covariates, difficulties in double blinding).

[Predictors of efficacy, mucosal healing and dose intensification during the first year of adalimumab therapy in patients with luminal and fistulizing Crohn's disease. National data from Hungary]. / A klinikai hatékonyság, a nyálkahártya-gyógyulás és a dózisemelés prediktorai az adalimumabkezelés elso évében Crohn-betegségben szenvedo betegekben Magyarországon.

UNLABELLED: Adalimumab is a fully human monoclonal antibody targeting tumor necrosis factor with proven efficacy in the treatment of Crohn's disease in clinical trials. The aim of the present study was to investigate the predictors of medium term clinical efficacy and mucosal healing during adalimumab therapy in patients with Crohn's disease in specialized centers approved for biological therapy in Hungary. METHODS: Data of 201 Crohn's disease patients were prospectively captured (male/female: 112/89, median age: 24 years, duration: 8 years). Previous infliximab therapy was given in 97 (48.3%) patients, concomitant steroids in 41.3% and azathioprine in 69.2% (combined: 26.4%) of patients. RESULTS: Overall clinical response and remission rates at 24 and 52 weeks were 78% and 52%, and 69.4% and 44.4%, respectively. Endoscopic improvement and healing was achieved in 43.1% and 23.6%, respectively. In a logistic regression model, clinical efficacy and normalized C-reactive protein at week 12, need for combined immunosuppression at induction, shorter disease duration and smoking were identified as independent predictors for 12-month clinical outcome, while normalized C-reactive protein at week 12, clinical remission at week 24, frequency of previous relapses and smoking were associated to endoscopic improvement/healing. Dose intensification to weekly dosing was needed in 16.4%. Parallel azathioprine therapy and clinical remission at week 12 was inversely associated to dose escalation to weekly dosing. CONCLUSION: Clinical efficacy and normalized C-reactive protein at week 12, need for combined immunosuppression, luminal disease and smoking are predictors for medium term clinical efficacy/mucosal healing during adalimumab therapy, while parallel azathioprine therapy may decrease the probability for dose escalation.

[Prediction of the disease course in inflammatory bowel diseases]. / A betegség lefolyásának elôrejelzése gyulladásos bélbetegségekben.

Clinical presentation at diagnosis and disease course of both Crohn's disease (CD) and ulcerative colitis (UC) are heterogeneous and variable over time. During follow up, intestinal strictures or perforation may eventually develop at most patients with CD, and significant number of patients will undergo surgery. Much emphasis was laid in recent years on the determination of important predictive factors. Since early introduction of immunomodulators and/or biologicals might be justified in patients at risk for disease progression, so it is important to identify these patients as soon as possible. This review article summarizes the available literature on important clinical, endoscopic, fecal, serological/routine laboratory and genetic factors and hopefully will assist clinicians in the decision making of daily practice when choosing the treatment strategy for their patients with inflammatory bowel diseases.

[Verner-Morrison syndrome: a case study]. / Verner-Morrison-szindróma egy esete.

Verner and Morrison described a syndrome of watery diarrhea, hypokalemia, and achlorhydria (WDHA) in 1958. VIPomas producing high amounts of vasoactive intestinal peptide (VIP) commonly originate from the pancreas. Typical symptoms play a momentous role in the diagnosis of VIPoma. Diarrhea may persist for years before the diagnosis. Morbidity from untreated WDHA syndrome is associated with long-standing dehydration and with electrolyte and acid-base metabolism disorders, which may cause chronic renal failure. Assessment of specific marker (VIP) offers high sensitivity in establishing the diagnosis. Imaging modalities include endoscopic ultrasonography, computed tomography and magnetic resonance imaging, and particularly, scintigraphy with somatostatin analogues. Treatment options include resection of the tumor, chemotherapy or the reduction of symptoms with somatostatin analogues. Early diagnosis and management may affect survival of patients favorably. VIPoma cases may be associated with multiple endocrine neoplasia type 1.

[Treatment adherence and use of complementary and alternative medicine in patients with inflammatory bowel disease]. / A terápiás adherencia, valamint a komplementer és alternatív gyógymódok használata gyulladásos bélbetegek kezelésében.

UNLABELLED: Previous studies have suggested an increasing use of complementary and alternative medicine (CAM) in patients with inflammatory bowel disease (IBD). Furthermore, a significant number of IBD patients fail to comply with treatment. The aim of our study was to evaluate the prevalence of non-adherence the use of CAM in Hungarian patients with IBD. METHODS: A total of 655 consecutive IBD patients (Crohn's disease [CD]: 344, age: 38.2 + or - 12.9 years; ulcerative colitis [UC]: 311, age: 44.9 + or - 15.3 years) were interviewed during the visit at specialists by self-administered questionnaire including demographic and disease-related data, as well as items analyzing the extent of non-adherence and CAM use. Patients taking more then 80% of each prescribed medicine were classified as adherent. RESULTS: The overall rate of self reported non-adherence (CD: 20.9%, UC: 20.6%) and CAM (CD: 31.7%, UC: 30.9%) use was not different between CD and UC. The most common causes of non-adherence were: forgetfulness (47.8%), too many/unnecessary pills (39.7%), being afraid of side effects (27.9%) and too frequent dosing. Most common forms of CAM were herbal tee (47.3%), homeopathy (14.6%), special diet (12.2%), and acupuncture (5.8%). In CD, disease duration, date of last follow-up visit, educational level and previous surgeries were predicting factors for non-adherence. Alternative medicine use was associated in both diseases with younger age, higher educational level and immunosuppressant use. In addition, CAM use in UC was more common in females and in patients with supportive psychiatric/psychological therapy. CONCLUSIONS: Non-adherence and CAM use is common in patients with IBD. Special attention should be paid to explore the identified predictive factors during follow-up visits to improve adherence to therapy and improving patient-doctor relationship.

[System analytical approach of lung function and hemodynamics]. / Rendszerszemléletu légzés- és vérkeringés-elemzés.

The authors critically analyse the traditional views in physiology and complete them with new statements based on computer model simulations of lung function and of hemodynamics. Conclusions are derived for the clinical practice as follows: the four-dimensional function curves are similar in both systems; there is a "waterfall" zone in the pulmonary blood perfusion; the various time constants of pulmonary regions can modify the blood gas values; pulmonary capillary pressure is equal to pulmonary arterial diastole pressure; heart is not a pressure pump, but a flow source; ventricles are loaded by the input impedance of the arterial systems and not by the total vascular (ohmlike) resistance; optimum heart rate in rest depends on the length of the aorta; this law of heart rate, based on the principle of resonance is valid along the mammalian allometric line; tachycardia decreases the input impedance; using positive end expiratory pressure respirators the blood gas of pulmonary artery should be followed; coronary circulation should be assessed in beat per milliliter, the milliliter per minute may be false. These statements are compared to related references.

Prevalence and predictors of hospitalization in Crohn's disease in a prospective population-based inception cohort from 2000-2012.

AIM: To analyze the prevalence, length and predictors of hospitalization in the biological era in the population-based inception cohort from Veszprem province. METHODS: Data of 331 incident Crohn's disease (CD) patients diagnosed between January 1, 2000 and December 31, 2010 were analyzed (median age at diagnosis: 28; IQR: 21-40 years). Both in- and outpatient records were collected and comprehensively reviewed. RESULTS: Probabilities of first CD-related hospitalization and re-hospitalization were 32.3%, 45.5%, 53.7% and 13.6%, 23.9%, 29.8%, respectively after one, three and five years of follow-up in Kaplan-Meier analysis. First-year hospitalizations were related to diagnostic procedures (37%), surgery or disease activity (27% and 21%). Non-inflammatory disease behavior at diagnosis (HR = 1.32, P = 0.001) and perianal disease (HR = 1.47, P = 0.04) were associated with time to first CD-related hospitalization, while disease behavior change (HR = 2.38, P = 0.002) and need for steroids (HR = 3.14, P = 0.003) were associated with time to first re-hospitalization in multivariate analyses. Early CD-related hospitalization (within the year of diagnosis) was independently associated with need for immunosuppressives (OR = 2.08, P = 0.001) and need for surgeries (OR = 7.25, P < 0.001) during the disease course. CONCLUSION: Hospitalization and re-hospitalization rates are still high in this cohort, especially during the first-year after the diagnosis. Non-inflammatory disease behavior at diagnosis was identified as the pivotal predictive factor of both hospitalization and re-hospitalization.

Does Hospitalization Predict the Disease Course in Ulcerative Colitis? Prevalence and Predictors of Hospitalization and Re-Hospitalization in Ulcerative Colitis in a Population-based Inception Cohort (2000-2012).

BACKGROUND AND AIMS: Limited data are available on the hospitalization rates in population-based studies. Since this is a very important outcome measure, the aim of this study was to analyze prospectively if early hospitalization is associated with the later disease course as well as to determine the prevalence and predictors of hospitalization and re-hospitalization in the population-based ulcerative colitis (UC) inception cohort in the Veszprem province database between 2000 and 2012. METHODS: Data of 347 incident UC patients diagnosed between January 1, 2000 and December 31, 2010 were analyzed (M/F: 200/147, median age at diagnosis: 36, IQR: 26-50 years, follow-up duration: 7, IQR 4-10 years). Both in- and outpatient records were collected and comprehensively reviewed. RESULTS: Probabilities of first UC-related hospitalization were 28.6%, 53.7% and 66.2% and of first re-hospitalization were 23.7%, 55.8% and 74.6% after 1-, 5- and 10- years of follow-up, respectively. Main UC-related causes for first hospitalization were diagnostic procedures (26.7%), disease activity (22.4%) or UC-related surgery (4.8%), but a significant percentage was unrelated to IBD (44.8%). In Kaplan-Meier and Cox-regression analysis disease extent at diagnosis (HR extensive: 1.79, p=0.02) or at last follow-up (HR: 1.56, p=0.001), need for steroids (HR: 1.98, p<0.001), azathioprine (HR: 1.55, p=0.038) and anti-TNF (HR: 2.28, p<0.001) were associated with the risk of UC-related hospitalization. Early hospitalization was not associated with a specific disease phenotype or outcome; however, 46.2% of all colectomies were performed in the year of diagnosis. CONCLUSION: Hospitalization and re-hospitalization rates were relatively high in this population-based UC cohort. Early hospitalization was not predictive for the later disease course.

Burden of Clostridium difficile infection between 2010 and 2013: Trends and outcomes from an academic center in Eastern Europe.

AIM: To analyze the incidence and possible risk factors in hospitalized patients treated with Clostridium difficile infection (CDI). METHODS: A total of 11751 patients were admitted to our clinic between 1 January 2010 and 1 May 2013. Two hundred and forty-seven inpatients were prospectively diagnosed with CDI. For the risk analysis a 1:3 matching was used. Data of 732 patients matched for age, sex, and inpatient care period and unit were compared to those of the CDI population. Inpatient records were collected from an electronic hospital database and comprehensively reviewed. RESULTS: Incidence of CDI was 21.0/1000 admissions (2.1% of all-cause hospitalizations and 4.45% of total inpatient days). The incidence of severe CDI was 12.6% (2.63/1000 of all-cause hospitalizations). Distribution of CDI cases was different according to the unit type, with highest incidence rates in hematology, gastroenterology and nephrology units (32.9, 25 and 24.6/1000 admissions, respectively) and lowest rates in 1.4% (33/2312) in endocrinology and general internal medicine (14.2 and 16.9/1000 admissions) units. Recurrence of CDI was 11.3% within 12 wk after discharge. Duration of hospital stay was longer in patients with CDI compared to controls (17.6 ± 10.8 d vs 12.4 ± 7.71 d). CDI accounted for 6.3% of all-inpatient deaths, and 30-d mortality rate was 21.9% (54/247 cases). Risk factors for CDI were antibiotic therapy [including third-generation cephalosporins or fluoroquinolones, odds ratio (OR) = 4.559; P < 0.001], use of proton pump inhibitors (OR = 2.082, P < 0.001), previous hospitalization within 12 mo (OR = 3.167, P < 0.001), previous CDI (OR = 15.32; P < 0.001), while presence of diabetes mellitus was associated with a decreased risk for CDI (OR = 0.484; P < 0.001). Treatment of recurrent cases was significantly different from primary infections with more frequent use of vancomycin alone or in combination (P < 0.001), and antibiotic therapy duration was longer (P < 0.02). Severity, mortality and outcome of primary infections and relapsing cases did not significantly differ. CONCLUSION: CDI was accounted for significant burden with longer hospitalization and adverse outcomes. Antibiotic, PPI therapy and previous hospitalization or CDI were risk factors for CDI.

Tuberculin Skin Test and Quantiferon in BCG Vaccinated, Immunosuppressed Patients with Moderate-to-Severe Inflammatory Bowel Disease.

BACKGROUND AND AIMS: There are few data available on the effect of immunomodulator/biological therapy on the accuracy of the tuberculin skin test (TST) and interferon-gamma release assay (IGRA) in BCG-vaccinated immunosuppressed patients with inflammatory bowel disease (IBD). Our aim was to define the accuracy, predictors and agreement of TST and IGRA in a BCG-vaccinated immunosuppressed referral IBD cohort. METHODS: 166 consecutive moderate-to-severe IBD patients (122 Crohn's disease, CD and 44 ulcerative colitis, UC) were enrolled in a prospective study from three centers. Patients were treated with immunosuppressives and/or biologicals. IGRA and TST were performed on the same day. Both in- and outpatient records were collected and comprehensively reviewed. RESULTS: TST positivity rate was 23.5%, 21.1%,14.5% and 13.9% when cut-off values of 5, 10, 15 and 20mm were used. IGRA positivity rate was 8.4% with indeterminate result in 0.6%. Chest X-ray was suggestive of latent tuberculosis in 2 patients. Correlation between TST and IGRA was moderate (kappa: 0.39-0.41, p<0.001). In addition, a cut-off of 14 and 17mm for TST was defined to identify IGRA positivity in a ROC analysis (AUC: 0.76, p=0.03). TST and/or IGRA positivity was not influenced by medical therapy or disease phenotype. Importantly, smoking was identified as a risk factor for TST but not IGRA positivity (OR: 2.70-5.02, p<0.01, for TSTcut-offs=5-20mm). CONCLUSION: TST and IGRA tests are partly complimentary methods, and additional testing by TST (with a cut-off of >15mm) should be considered to identify patients at risk for latent TB. Accuracy is satisfactory in BCG-vaccinated, immunosuppressed IBD patients. Smoking is a risk factor for TST positivity.

Frequency and prognostic role of mucosal healing in patients with Crohn's disease and ulcerative colitis after one-year of biological therapy.

AIM: To assess the endoscopic activity before and after a one-year period of biological therapy and to evaluate the frequency of relapses and need for retreatment after stopping the biologicals in patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: The data from 41 patients with CD and 22 patients with UC were assessed. Twenty-four CD patients received infliximab, and 17 received adalimumab. The endoscopic severity of CD was quantified with the simplified endoscopic activity score for Crohn's disease in CD and with the Mayo endoscopic subscore in UC. RESULTS: Mucosal healing was achieved in 23 CD and 7 UC patients. Biological therapy had to be restarted in 78% of patients achieving complete mucosal healing with CD and in 100% of patients with UC. Neither clinical remission nor mucosal healing was associated with the time to restarting the biological therapy in either CD or UC. CONCLUSION: Mucosal healing did not predict sustained clinical remission in patients in whom the biological therapies had been stopped.

Decreasing trends in hospitalizations during anti-TNF therapy are associated with time to anti-TNF therapy: Results from two referral centres.

BACKGROUND: Hospitalization is an important outcome measure and a major driver of costs in patients with inflammatory bowel disease. We analysed medical and surgical hospitalization rates and predictors of hospitalization before and during anti-TNF therapy. METHODS: Data from 194 consecutive patients were analysed retrospectively (males, 45.4%, median age at diagnosis, 24.0 years, infliximab/adalimumab: 144/50) in whom anti-TNF therapy was started after January 1, 2008. Total follow-up was 1874 patient-years and 474 patient-years with anti-TNF exposure. RESULTS: Hospitalization rates hospitalization decreased only in Crohn's disease (odds ratio: 0.59, 95% confidence interval: 0.51-0.70, median 2-years' anti-TNF exposure) with a same trend for surgical interventions (p=0.07), but not in ulcerative colitis. Need for hospitalization decreased in Crohn's disease with early (within 3-years from diagnosis, p=0.016 by McNemar test), but not late anti-TNF exposure. At logistic regression analysis complicated disease behaviour (p=0.03), concomitant azathioprine (p=0.02) use, but not anti-TNF type, gender, perianal disease or previous surgeries were associated with the risk of hospitalization during anti-TNF therapy. CONCLUSION: Hospitalization rate decreased significantly in patients with Crohn's disease but not ulcerative colitis after the introduction of anti-TNF therapy and was associated with time to therapy. Complicated disease phenotype and concomitant azathioprine use were additional factors defining the risk of hospitalization.

Incidence rates and disease course of paediatric inflammatory bowel diseases in Western Hungary between 1977 and 2011.

BACKGROUND: Limited data are available on paediatric inflammatory bowel diseases in Eastern Europe. Our aim was to analyse disease characteristics in the population-based Veszprem province database between 1977 and 2011. METHODS: 187 (10.5%, ulcerative colitis/Crohn's disease/undetermined colitis: 88/95/4) out of 1565 incident patients were diagnosed with a paediatric onset in this population-based prospective inception cohort. RESULTS: The incidence of Crohn's disease and ulcerative colitis increased from 0 and 0.7 in 1977-1981 to 7.2 and 5.2 in 2007-2011 per 100,000 person years. Ileocolonic location (45%) and inflammatory disease behaviour (61%) were most frequent in Crohn's disease, while azathioprine use was frequent (66%) and surgical resection rates were high (33% at 5 years) in cases with paediatric onset. In ulcerative colitis, 34% of patients were diagnosed with extensive disease, with high rates of disease extension (26% and 41% at 5 and 10 years), fulminant episodes (19.3%) and systemic steroid use (52.3%). The cumulative rate of colectomy was low (6.9%). CONCLUSIONS: The incidence of paediatric inflammatory bowel diseases has rapidly increased in the last three decades in Western Hungary. Ileocolonic disease and a need for azathioprine were characteristic in paediatric Crohn's disease, while paediatric onset ulcerative colitis was characterised by extensive disease and disease extension, while the need for colectomy was low.

Methotrexate: should we start using it in clinical practice?

Therapeutic approaches in inflammatory bowel disease have changed significantly in the past decade. Early aggressive immunosuppression has become the mainstay of therapy for patients at risk for complicated disease. Azathioprine is the most widely used immunosuppressant; however, a subgroup of patients is intolerant or refractory. Since the late 1990s, methotrexate (MTX) has become more widely used as an immunomodulator in patients with chronic inflammatory diseases such as rheumatoid arthritis and psoriasis. Yet according to recent clinical data, methotrexate remained the second most commonly used immunosuppressive in inflammatory bowel diseases. Two landmark trials and subsequent studies provided evidence for the use of methotrexate in Crohn's disease, both for induction and maintenance of remission. The evidence is less solid in ulcerative colitis, for which results of further randomized controlled trials are pending (e.g. Meteor, Merit). A potential new indication of MTX could be combination therapy with biologicals. While this is state of the art therapy in rheumatoid arthritis, data in inflammatory bowel diseases are less clear. Some studies suggest that combination with immunosuppressants could prevent the development of anti-drug antibodies, while others suggested anti- TNF induced autoimmune disorders as a potential indication. In contrast, improved efficacy was not reported by one study (COMMIT). Limitations include frequent side effects, route of administration, pregnancy and concerns about long-term safety. This review summarizes current knowledge on the efficacy and side effects of methotrexate, and tries to reevaluate the drug in the current IBD armamentarium.

Recommendations for identifying Crohn's disease patients with poor prognosis.

Clinical presentation at diagnosis and the disease course of Crohn's disease is heterogeneous and variable over time. The majority of patients with Crohn's disease will develop at least one stricturing or perforating complication requiring surgery during follow-up. New data support a change in the natural history of the disease associated with the advent of biologicals and tailored treatment strategy. Therefore, it is important to identify patients at risk for disease progression as soon as possible. In recent years, much emphasis has been placed on determining important predictive factors. Complex evaluation of factors such as clinical and endoscopic presentation, fecal, serological and routine laboratory tests, and genetic factors is needed. This review summarizes the available evidence and will hopefully assist clinicians when choosing a treatment strategy in everyday practice.

Is current smoking still an important environmental factor in inflammatory bowel diseases? Results from a population-based incident cohort.

BACKGROUND: Previous studies suggest that smoking is an important environmental factor in inflammatory bowel diseases (IBDs), with dichotomous effects in ulcerative colitis (UC) and Crohn's disease (CD). The aim of this study was to analyze the relationship between smoking and IBD risk in a population-based database from Veszprem Province, which included incident cases diagnosed between January 1, 1977, and December 31, 2008. METHODS: Data from 1420 incident patients were analyzed (UC: 914, age at diagnosis: 38.9 years; CD: 506, age at diagnosis: 31.5 years). Both inpatient and outpatient records were collected and comprehensively reviewed. Overall, smoking frequency in the adult general population was 36.1%. RESULTS: Of patients with CD, 47.2% were current smokers at diagnosis. Smoking was more frequent in male patients (P = 0.002) and was associated with an increased risk of CD (odds ratio, 1.96; 95% confidence interval, 1.63-2.37; P < 0.001). In contrast, current smoking was protective against UC (odds ratio, 0.33; 95% confidence interval, 0.27-0.41). The effect of smoking was linked to gender (in CD, more deleterious in male patients) and age at diagnosis and was most prominent in young adults, with a difference already being seen in 18- to 19-year-olds. In CD, a change in disease behavior (P = 0.02), location from ileal or colonic to ileocolonic (P = 0.003), arthritis/arthropathy (P = 0.002), need for steroids (P = 0.06), or AZA (P = 0.038) was more common in current smokers. Smoking in UC was associated with more extensive disease (P = 0.01) and a tendency for decreased need for colectomy (P = 0.06). CONCLUSIONS: Current smoking was associated with the risk of IBD. This effect was linked to gender and age at diagnosis and was most prominent in young adults. No association was observed in pediatric or elderly patients. The deleterious and protective effects of smoking on the course in CD and UC were partially confirmed.