Chronic Inflammatory Intestinal Disorders in Hidradenitis Suppurativa.

BACKGROUND: Intestinal symptoms are common in patients with hidradenitis suppurativa (HS). HS patients may experience a broad spectrum of chronic inflammatory intestinal disorders (CIID), not exclusive to inflammatory bowel diseases, which are diagnosed by colonoscopy and intestinal biopsies. The frequency of CIID in patients with HS has not been investigated. OBJECTIVE: The objectives of this study were to determine the occurrence of CIID in HS and characterize this clinical population. Furthermore, the feasibility of using faecal calprotectin (FC) test or anti-Saccharomyces cerevisiae antibody (ASCA) levels to assess the colonic inflammation of CIID in HS patients was investigated. METHODS: All newly diagnosed and untreated HS patients (n = 74) were referred to a gastroenterologist for FC followed by colonoscopy after informed consent. C-reactive protein (CRP), white blood cell count, nucleotide-binding oligomerization-domain-containing protein 2 (NOD2) polymorphism, and ASCA levels were measured. Patients were divided into HS-only and HS with CIID (HS + CIID) groups, based on the absence or presence of CIID. Laboratory and clinical parameters (age, gender, HS onset, clinical stage, family history, body mass index (BMI), smoking) were compared between the groups. RESULTS: Thirteen patients complained gastrointestinal symptoms prior to any examination, including 11 in the HS + CIID group. The CIID frequency in HS was 28.4% (n = 21/74), based on colonoscopy and histology. Significantly more patients had severe disease state in the HS + CIID group compared with the HS-only group, and BMI was significantly lower in the HS + CIID group (28.20 ± 5.58 vs. 32.74 ± 6.45, p = 0.006). FC positivity occurred significantly more in HS + CIID patients compared with HS-only patients (90.48% vs. 3.77%, p < 0.001), and ASCA IgG levels were significantly elevated in HS + CIID patients (22.08 ± 23.07 vs. 8.41 ± 10.94 U/mL, p = 0.001). The FC test identified HS + CIID patients with 96.23% specificity and 91.3% sensitivity, while ASCA displayed 77.8% sensitivity and 76.3% specificity. Blood count, CRP, and the presence of NOD2 polymorphisms were indifferent between the two groups. CONCLUSION: A high frequency of CIID was detected in the examined HS population. The noninvasive FC test has high sensitivity and specificity for diagnosing CIID in HS patients. Concomitant CIID and HS may indicate the need for an early-start for biological treatment.

Validity of the EQ-5D-5L and EQ-5D-3L in patients with Crohn's disease.

PURPOSE: The EuroQol five-dimension questionnaire (EQ-5D) is the most commonly used instrument to obtain utility values for cost-effectiveness analyses of treatments for Crohn's disease (CD). We aimed to compare the measurement properties of the two adult versions of EQ-5D (EQ-5D-3L and EQ-5D-5L) in patients with CD. METHODS: Between 2016 and 2017, a multicentre cross-sectional survey was carried out. Consecutive outpatients with CD completed the 3L, 5L and EQ visual analogue scale (VAS). Disease severity was graded by the Crohn's Disease Activity Index (CDAI) and Perianal Disease Activity Index (PDAI). The 3L and 5L were compared in terms of feasibility, agreement, ceiling effect, redistribution properties, discriminatory power, convergent and known-groups validity. RESULTS: Two-hundred and six patients (54.9% male, mean age 35 ± 11 years) participated in the survey. For 3L, 25 unique health states were observed versus 59 for the 5L. The overall ceiling effect decreased from 29.6% (3L) to 25.5% (5L). Absolute discriminatory power improved (mean Shannon index 0.84 vs. 1.18). The 3L correlated stronger with EQ VAS and CDAI scores, whereas the 5L with PDAI. The 5L demonstrated a better known-groups validity on the basis of age, perianal fistulas, extraintestinal manifestations and disability. CONCLUSIONS: This is the first study to report the impact of CD on quality of life using the EQ-5D-5L questionnaire. The 5L seems to perform better than 3L in terms of feasibility, ceiling effect, discriminatory power and known-groups validity. Understanding the differences in psychometrics between the 3L and 5L is essential as they have substantial implications for financial decision-making about CD treatments.

The potential role of FDG PET-CT in the characterization of the activity of Crohn's disease, staging follow-up and prognosis estimation: a pilot study.

OBJECTIVES: FDG PET-CT is a global, noninvasive, sensitive method to determine the location and activity of inflammatory lesions. Segmental FDG uptake is proportional with immune cell infiltration of bowel. Our aim was to evaluate prospectively the role of PET in patients with active Crohn's disease (CD) before and after one year's biological therapy, and to compare simple endoscopic score for CD (SES-CD), CD activity index (CDAI) and global PET scores. We also analyzed the prognostic value of initial PET scores. PATIENTS: Twelve patients were selected: six male/six female, ages between 18 and 39, average: 24 years, with CDAI values >300. METHODS: We scored the FDG uptake in the small intestine and the four colon segments (on a scale 0-3 for each), and summed them thus forming a global PET score. The scoring was based on the maximal standardized uptake value of the intestinal segment, related to the SUVmax of the liver (as a reference for normal tissue activity). The SES-CD, CDAI and global PET scores before and after treatment were statistically compared. RESULTS: There were significant changes in CDAI and SES-CD after therapy, PET scores improved only in patients' subgroup with high (>4) initial PET score, indicating good prognosis of biological treatment. In active disease, PET was more informative than endoscopy to access the extent of the inflammation, and small intestine involvement. CONCLUSIONS: FDG PET-CT score is a promising, noninvasive complementary method in the staging, treatment planning and follow-up of CD. Limitation of the study is the small number of patients.

[Significance of the monitoring and screening for hereditary nonpolyposis colorectal carcinoma syndrome patients by presenting a case of a family tree]. / A hereditaer nonpolyposus colorectalis carcinoma szindrómás betegek szurésének és szoros utánkövetésének fontossága egy családfa bemutatása kapcsán.

INTRODUCTION: Hereditary nonpolyposis colorectal carcinoma (HNPCC) is an autosomal dominant disease, which shows familial clustering. AIM: We would like to emphasize the importance of monitoring the HNPCC syndrome patients by presenting a case of a proven MMR gene mutation carrier and her family tree encompassing 10 years. MATERIALS AND METHOD: To screen a suspected HNPCC Hungarian family member we are taking thorough family histories. If the diagnosis of HNPCC was further supported by immunohistology and the microsatellite status, sequencing of the MMR genes was carried out. RESULTS: A novel mutation in exon 6 of the hMSH2 gene leading to the deletion of two nucleotide pairs [c.969-970delTC] was detected in our patient. During the 10-year follow-up period of our patient new HNPCC-associated tumors have developed in several family members. Conslusion: Close surveillance of the patient and its family members at risk was effective, although it requires compliance from the subjects. Orv Hetil. 2017; 158(30): 1182-1187.

[Long-term adalimumab therapy in ulcerative colitis in clinical practice: result of the Hungarian multicenter prospective study]. / Az adalimumab hatékonysága és biztonságossága hagyományos kezelésre refrakter colitis ulcerosában.

INTRODUCTION: Adalimumab was approved for the treatment of ulcerative colitis refractory to conventional therapy several years later than infliximab in Europe. Due to the relatively low remission rate observed in Ultra trials, data on the efficacy of adalimumab in ulcerative colitis are really helpful in the daily practice. AIM: The aim of this study was to prospectively collect data on induction and maintenance adalimumab therapy in patients with ulcerative colitis treated in Hungarian centres. METHOD: This prospective study collected data of all patients with ulcerative colitis treated with adalimumab in 10 Hungarian centres. The primary endpoints of the study were rates of remission, response and primary failure at week 12, and the rate of continuous clinical response, remission and loss of response at weeks 30, and 52. Secondary endpoints were endoscopic outcome at week 52 and comparison of the efficacy of adalimumab between treatment naive and infliximab-experienced patients. RESULTS: 73 patients with active ulcerative colitis were enrolled in the study. 75.3% of the patients exhibited clinical response after the induction at week 12. The probability of maintaining adalimumab treatment was 48.6% at week 52 with a continuous clinical response in 92% of these patients. Mucosal healing was achieved in 48.1% of the patients at week 52. Dose intensification was performed in 17.6% of the patients. Minor side effects developed in 4% of the patients and 5.4% of the patients underwent colectomy during the 1-year treatment period. CONCLUSIONS: These results coming from the real clinical setting demonstrate a favourable efficacy of adalimumab induction and maintenance therapy in patients with ulcerative colitis.

Combination of IgG N-glycomics and corresponding transcriptomics data to identify anti-TNF-α treatment responders in inflammatory diseases.

Prediction of responsiveness in biological therapies is an important and challenging issue in different diseases. Analyzing glycosylation pattern changes of key serum glycoproteins is one of the possible avenues to follow disease remission. The aim of this study was to investigate the changes of serum IgG glycoforms in Crohn's disease (CD) and rheumatoid arthritis patients in response to antitumor necrosis factor alpha (anti-TNF-α) treatment. IgG was isolated from patient serum samples using Protein A affinity pull-down, followed by the release of N-glycans with peptide-N-glycosidase F. The released glycans were fluorescently tagged with 8-aminopyrene-1,3,6-trisulfonate and analyzed by CGE with laser-induced fluorescent detection. Significant alterations were detected between responders and nonresponders in both disease groups. In CD patients, disease-specific alteration was found in response to anti-TNF-α therapy, which was also confirmed by transcriptomics data analysis of the corresponding glycosyltransferases and glycosidases.

Primary angiosarcoma of the pancreas mimicking severe acute pancreatitis--case report.

Primary angiosarcoma of the pancreas is an extremely rare neoplasm that often mimicks severe acute pancreatitis. A 58-year-old man was admitted with clinical and laboratory signs of severe acute pancreatitis. Contrast enhanced CT scan demonstrated haemorrhagic necrotizing inflammation of the pancreas involving the pancreatic tail, splenic hilum and small bowels with multiple peripancreatic and free abdominal fluid collection. Percutaneous drainage was performed. After 13 days, laparotomy was indicated because of persistent intra-abdominal bleeding, fever and a palpable, rapidly growing mass in the left upper quadrant of the abdomen. During the operation a necrotic, haemorrhagic mass was found in the pancreatic tail; a frozen section showed malignancy, although the tumour was unresectable. Despite all conservative and surgical therapeutic attempts, the patient died within four weeks after diagnosis. Final histology justified primary angiosarcoma of the pancreas. If a patient with signs of severe acute pancreatitis has fever without elevated PCT, the presence of a malignant tumour of the pancreas should be considered.

Predictors of relapse in patients with ulcerative colitis in remission after one-year of infliximab therapy.

BACKGROUND. Some of the most important questions relating to the use of biological therapy in inflammatory bowel diseases concern the duration of maintenance therapy. The RASH study revealed that previous use of biological therapy and dose intensification are associated with restarting of biological therapy in Crohn's disease. The aim of the study was to assess the disease course and frequency of relapse of ulcerative colitis (UC) following discontinuation of infliximab in patients with remission and to determine predictive factors for relapse. PATIENTS AND METHODS. Fifty-one UC patients who had achieved clinical remission following 1 year of infliximab therapy and for whom infliximab was then discontinued participated in this prospective observational study. 15.7% of the patients received infliximab before the 1-year period of biological therapy analyzed in the study. Biological therapy was restarted in case of recurrent clinical activity. Data were collected from four Hungarian IBD centers. RESULTS. Thirty-five percent of the patients needed to be retreated with infliximab within 1 year after treatment cessation. Logistic regression analysis revealed that previous biological therapy (p = 0.021) was associated with the need of restarting infliximab. None of the data relating to patients' demographic and clinical characteristics, concomitant therapy and CRP level showed association with the need for restarting biological therapy. CONCLUSIONS. Biological therapy was restarted at a median of 4 months after discontinuation in more than every third UC patients who had been in clinical remission following 1 year of infliximab therapy. Response to retreatment with infliximab was favorable in the majority of the patients who relapsed.

[Severe anemia caused by haemorrhoids: the casae of a young man with toxic cirrhosis]. / Súlyos anaemia aranyeres csomókból: fiatal, toxikus cirrhosisos férfi beteg esete.

A 38-year-old alcoholic man with severe iron deficient anaemia, and bloody-mucous stool was found to have haemorrhoidal bleeding. In spite of intravenous iron supplements haemoglobin levels were falling. He was admitted because of deteriorating condition, jaundice, severe anaemia (haemoglobin, 38 g/l) and iron deficiency. Except of toxic (alcohol) agent all other causes of liver disease could be excluded. Sclero-, and medical therapy, and abstinence resulted in a rapid improvement in his condition and subsequently rectal bleeding also disappeared. Bleeding from the upper gastrointestinal tract is a well known and serious complication in liver cirrhosis, however, a voluminous blood loss resulting in a life-threatening anaemia from lower gastrointestinal tract or haemorrhoids, as it was detected in this patient, is quite rare. Sclerotherapy seems to be an effective method with only minor complications when compared with other invasive techniques. However, the patient's compliance even in liver cirrhosis with haemorrhoidal nodes is essential for long-term success.

Early versus Late Use of Vedolizumab in Ulcerative Colitis: Clinical, Endoscopic, and Histological Outcomes.

BACKGROUND AND AIMS: We explored the potential for differential efficacy of vedolizumab between "early" and "late" ulcerative colitis (UC) with evaluation of clinical, endoscopic, and histological endpoints. METHODS: This was a multicentre, multinational open-label study in patients with moderately-to-severely active UC, defining "early" UC by a disease duration <4 years and bio-naïve and "late" UC by a disease duration >4 years and additional exposure to tumour necrosis factor antagonists. Patients received standard treatment with intravenous vedolizumab for 52 weeks (300 mg weeks 0-2-6, every 8 weeks thereafter without escalation). The primary endpoint was corticosteroid-free clinical remission with endoscopic improvement (total Mayo score ≤2 with no subscore >1) at both week 26 and 52. RESULTS: A total of 121 patients were included: in the "early" group 25/59 (42.4%) achieved the primary endpoint versus 19/62 (30.6%) in the "late" group (P = 0.18). There were no significant differences between the two groups in endoscopic improvement (week 26: "early" 32/59 [54.2%] vs. "late" 29/62 [46.8%]; P = 0.412; week 52: 27/59 [45.8%] vs. 25/62 [40.3%]; P = 0.546) or histological remission (Robarts Histopathology Index <3 without neutrophils in the epithelium and lamina propria) (week 26: 24/59 [40.7%] vs. 21/62 [33.9%]; P = 0.439; week 52: 22/59 [37.3%] vs. 22/62 [35.5%]; P = 0.837). CONCLUSIONS: No significant differences in clinical, endoscopic, and histological outcomes were observed between "early" and "late" disease.

Is there any association between impaired health-related quality of life and non-adherence to medical therapy in inflammatory bowel disease?

OBJECTIVES: Inflammatory bowel diseases (IBD) have a huge impact on the patients' lives and require continuous medication and long-term medical follow-up. The Short Form Health Survey (SF-36) is a commonly used questionnaire measuring health-related quality of life (HRQOL). Our aim was to evaluate whether HRQOL influences medication adherence and vice versa in IBD patients, and to find relationships between demographic parameters, therapeutic modalities and non-adherence or HRQOL. PATIENTS AND METHODS: Five hundred ninety-two IBD patients treated at six Hungarian tertiary centers were enrolled. Patients completed the SF-36 questionnaire and a medication adherence report scale during their visits. The associations between demographic parameters, HRQOL, different kinds of therapies and non-adherence were analyzed. RESULTS: The most affected dimension was physical functioning and least affected were the social functions. About 42.7% of the patients revealed their HRQOL to be acceptable. About 74.6% of the patients believed that the prescribed medications actually improved their HRQOL. Diarrhea was the most common and most severe symptom during the course of the disease. Non-adherence was reported in 13.4% of the patients. 'Forgetting to take the medication' was the main reason for non-adherence in 67.6% of the cases. Medication adherence was significantly higher among nonsmoker patients, and also in the case of immunomodulator therapy. There was no association between the sum of HRQOL and different subscores and non-adherence. CONCLUSION: Inflammatory bowel disease is associated with low HRQOL, which is not affected by drug therapy. The impaired quality of life in IBD is mainly influenced by the disease itself.

[Hungarian data on inflammatory bowel diseases: analytical data on ulcerative colistis]. / Magyarországi adatok a gyulladásos bélbetegségrol, analitikai adatok a colitis ulcerosáról.

UNLABELLED: Prospective data collection seems to be essential in evidence-based medicine. Because of the new therapeutic options, the need for standard data collection and testing has significantly increased. In Hungary, a registry for patients with inflammatory bowel disease has already been set up, which makes it possible for clinicians to collect prospective data on their patients. AIM: Basic characteristics of the database of patients with ulcerative colitis are presented in this paper. METHODS: The inflammatory bowel disease registry uses the programme of Microsoft Access database management system. Data are stored in a central server. RESULTS: The incidence of inflammatory bowel diseases has been permanently increasing in Hungary; however, its overall prevalence is still low among the European countries. The frequent administration of immunosuppressive medications (azathioprine and corticosteroids) and their increased doses worsen the estimation of the activity. CONCLUSIONS: 1., It would be very useful to gain prospective data from all national centres. This kind of database would be able to give a complete picture regarding the Hungarian therapeutical practice. 2., Medications of patients may alter the clinical value of the laboratory findings in the process of determining the severity of the disease.

Neoadjuvant (preoperative) chemoradiotherapy of advanced rectal tumors / Elorehaladott végbéldaganatok neoadjuváns (preoperatív) kemoradioterápiája

Introduction: There have been significant changes in the treatment protocol for rectal tumors in recent decades, greatly reducing the rate of local recurrence and distant metastasis, thereby increasing overall survival. Method: We performed a retrospective processing and statistical analysis of the data of 362 patients with rectal cancer who underwent local neoadjuvant chemoradiotherapy and then underwent surgical treatment between 1 January 2010 and 31 December 2017 at the Institute of Surgery of the University of Debrecen. We compared the response rate and overall survival results of our patients with local neoadjuvant treatment to the outcomes of total neoadjuvant treatment reported by the recent large international studies. Results: We experienced complete pathological regression in 8.6% of our patients. After neoadjuvant therapy, 10.7% of our patients experienced distant metastasis at the time of the operation or within 3 months period thereafter. In our study, the rate of response to the neoadjuvant treatment was a prognostic factor independent of the stage at di-agnosis and recognition. The groups with better response produced significantly better survival results. Conclusion: The total neoadjuvant treatment doubled the number of patients with complete pathological response, and the incidence of distant metastasis was by 7% lower in both recent international studies compared to the local neoadjuvant group. 85% of our patients were T3-4N+ stage at the time of recognition. Given the 10.7% rate of dis- tant metastases detected at the time of surgery or within 3 months in our patient population, we can state that ap- proximately half of our patients would have benefited from the administration of total neoadjuvant therapy which produced better outcomes. Based on this conclusion, we decided to introduce the total neoadjuvant therapy protocol in our department for treatment of patients with advanced rectal tumors.

[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.

Mannose-binding lectin deficiency confers risk for bacterial infections in a large Hungarian cohort of patients with liver cirrhosis.

BACKGROUND & AIMS: Mannose-binding lectin (MBL) is a serum lectin synthesized by the liver and involved in innate host defense. MBL deficiency increases the risk of various infectious diseases mostly in immune-deficient conditions. Bacterial infections are a significant cause of morbidity and mortality in liver cirrhosis due to the relative immuncompromised state. METHODS: Sera of 929 patients with various chronic liver diseases [autoimmune liver diseases (ALD), 406; viral hepatitis C (HCV), 185; and liver cirrhosis (LC) with various etiologies, 338] and 296 healthy controls (HC) were assayed for MBL concentration. Furthermore, a follow-up, observational study was conducted to assess MBL level as a risk factor for clinically significant bacterial infections in cirrhotic patients. RESULTS: MBL level and the prevalence of absolute MBL deficiency (<100 ng/ml) was not significantly different between patients and controls (ALD: 14.5%, HCV: 11.9%, LC: 10.7%, HC: 15.6%). In cirrhotic patients, the risk for infection was significantly higher among MBL deficient subjects as compared to non-deficient ones (50.0% vs. 31.8%, p=0.039). In a logistic regression analysis, MBL deficiency was an independent risk factor for infections (OR: 2.14 95% CI: 1.03-4.45, p=0.04) after adjusting for Child-Pugh score, co-morbidities, gender, and age. In a Kaplan-Meier analysis, MBL deficiency was associated with a shorter time to develop the first infectious complication (median days: 579 vs. 944, pBreslow=0.016, pLogRank=0.027) and was identified as an independent predictor in a multivariate Cox-regression analysis (p=0.003, OR: 2.33, 95% CI: 1.34-4.03). CONCLUSIONS: MBL deficiency is associated with a higher probability and shorter time of developing infections in liver cirrhosis, further supporting the impact of the MBL molecule on the host defense.

[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.

Anti-TNF dose escalation and drug sustainability in Crohn's disease: Data from the nationwide administrative database in Hungary.

BACKGROUND: A significant percentage of patients receiving anti-tumor necrosis factor alpha (anti-TNFα) agents lose clinical response over time. This study aims to provide representative real-world data on anti-TNFα drug sustainability, prevalence and predictors of anti-TNFα dose escalation. METHODS: In this nationwide, retrospective study, patients receiving infliximab or adalimumab therapy between 2013 and 2016 were included using the administrative claims database of the Hungarian National Health Insurance Fund. Demographic characteristics, drug sustainability, dose escalation, use of parallel medications were analyzed. RESULTS: 476 infliximab and 397 adalimumab patients were included. Dose escalation was observed in 7%, 9% and 22% of patients receiving originator/biosimilar infliximab and adalimumab during the complete follow-up, respectively. Dose escalation was associated with shorter disease duration (OR = 1.75, p = 0.026) and corticosteroid use. Drug retention rates were 62.7%, 72.3%, 75.4% after 1 year follow-up for Remicade®, Inflectra® and Humira®, which decreased to 38.3% and 52.1% for Remicade® and Humira® at 3 years. Drug sustainability was affected by steroid use prior biologic initiation in adalimumab treated patients (HR = 2.04, p < 0.001), while in infliximab treated patients dose escalation (HR = 0.51, p = 0.02) and gender (HR = 1.39, p = 0.033) were predictors of treatment discontinuation. CONCLUSION: Dose escalation rates were lower in this real-world administrative database study for both adalimumab and infliximab compared to published data. Drug retention rates were overall satisfactory, with no apparent difference between the legacy and biosimilar infliximab.

Real-life efficacy of vedolizumab on endoscopic healing in inflammatory bowel disease - A nationwide Hungarian cohort study.

Background: GEMINI trials demonstrated the therapeutic efficacy of vedolizumab (VDZ) in Crohn's disease (CD) and ulcerative colitis (UC).Research design and methods: Aim of this study was to determine the real-life effectiveness of VDZ on endoscopic healing in the Hungarian nationwide cohort of inflammatory bowel disease (IBD) patients based on the changes on clinical and endoscopic scores. Every adult IBD patient in the country (121 UC and 83 CD) who completed the short-term VDZ therapy was enrolled, of which 72 UC and 52 CD patients could complete the long-term therapy.Results: The rates of endoscopic healing were substantially higher in UC compared with CD patients during the short- and long-term therapy (52.9% vs. 21.7%, p < 0.0001, and 51.4% vs. 21.2%, p = 0.015, respectively). In CD, the rate of endoscopic healing was lower at week 14 compared with week 22 (14.5% vs. 37.0%, p = 0.026). Prior anti-TNF-α therapy (88.73%) was not associated with a significant decrease in therapeutic response. The average disease duration was significantly lower in CD patients achieving endoscopic healing at week 52 (11.75 vs. 5.27 years, p = 0.007).Conclusions: VDZ therapy is an effective therapeutic option in anti-TNF-α refractory IBD. However, the endoscopic healing rate was substantially lower and showed a significant delay in CD compared with UC.

Efficacy and safety of infliximab induction therapy in Crohn's Disease in Central Europe--a Hungarian nationwide observational study.

BACKGROUND: Infliximab (IFX) has proven to be an effective addition to the therapeutic arsenal for refractory, fistulizing, and steroid dependent Crohn's disease (CD), with efficacy in the induction and maintenance of clinical remission of CD. Our objective in this study is to report the nationwide, multicenter experience with IFX induction therapy for CD in Hungary. METHODS: During a 6-year-period, beginning in 2000, a total of 363 CD patients were treated with IFX as induction therapy (5 mg/kg IFX infusions given at week 0, 2 and 6) at eleven centers in Hungary in this observational study. Data analysis included patient demographics, important disease parameters and the outcome of IFX induction therapy. RESULTS: Three hundred and sixty three patients (183 women and 180 men) were treated with IFX since 2000. Mean age was 33.5 +/- 11.2 years and the mean duration of disease was 6.7 +/- 6.1 years. The population included 114 patients (31.4%) with therapy-refractory CD, 195 patients (53.7%) with fistulas, 16 patients (4.4%) with both therapy-refractory CD and fistulas, and 26 patients (7.2%) with steroid dependent CD. Overall response rate was 86.2% (313/363). A higher response rate was observed in patients with shorter disease duration (p = 0.05, OR:0.54, 95%CI:0.29-0.99) and concomitant immunosuppressant therapy (p = 0.05, OR: 2.03, 95%CI:0.165-0.596). Concomitant steroid treatment did not enhance the efficacy of IFX induction therapy. Adverse events included 34 allergic reactions (9.4%), 17 delayed type hypersensitivity (4.7%), 16 infections (4.4%), and 3 malignancies (0.8%). CONCLUSION: IFX was safe and effective treatment in this cohort of Hungarian CD patients. Based on our experience co-administration of immunosuppressant therapy is suggested in patients receiving IFX induction therapy. However, concomitant steroid treatment did not enhanced the efficacy of IFX induction therapy.

[Open transgastric necrosectomy for extended walled-off pancreas necrosis]. / Kiterjedt, demarkált pancreas necrosis sebészi kezelése transgastricus necrectomiával.

AIMS: In severe acute pancreatitis the timing of necrosectomy is ideally should be postponed 4-6 weeks after the onset of the disease when the walled-of pancreatic necrosis (WOPN) has developed. The authors present their experience with open transgastric necrosectomy for extended WOPN. PATIENTS AND METHODS: The authors performed 17 (12 male, 5 female with a mean age of 61.6 ± 15.1 years) open transgastric necrosectomies for extended WOPN in a period of 1, January 2012 and 31, December 2017. Before the operations conservative and semiconservative therapy was used for an average of 74.6 ± 83.1 days. The mean size of the WOPNs was 13.8 ± 5.2 cm with localisation of the retrocolic and retroduodenal regions. All necroses were septic. RESULTS: Complications related to the operation were not observed. The mean time of hospitalization after the surgery was 11.6 ± 12.8 days. The mortality rate was 5.9%. Late operation or other interventions for pseudocyst or pancreas fistula formation was not performed. Two patients needed endoscopic dilatation with lavage in the early postoperative period because of fever. New diabetes mellitus was not observed but worsening of previously existed diabetes developed in 6.3% of the cases. CONCLUSIONS: The open transgastric necrosectomy is safe and effective for extended WOPN. The advantage of this type of necrosectomy is the prevention of pancreatic pseudocyst and fistula formation.