P Lakatos

Corvinus University of Budapest, Budapeŝto, Budapest, Hungary

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Publications (346)1543.01 Total impact

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    ABSTRACT: Background: A better knowledge of the natural history of disabling chronic diseases is essential to improve patient management, evaluate the impact of treatment strategies and provide predictors for disabling disease and comprehensive information for patients. Aim: To summarise our current knowledge issued from population-based studies of the natural history of ulcerative colitis (UC) in children. Methods: We searched MEDLINE (source PubMed) and international conference abstracts, and included all population-based studies that evaluated long-term outcome of paediatric-onset (<17 years at diagnosis) UC. Results: A total of 26 population-based studies were considered in this review from the total of 61 articles or abstracts screened. Most patients presented disease extension and about two-thirds of patients had pancolitis at the end of follow-up. One-half of patients experienced extra-intestinal manifestations and primary sclerosing cholangitis was observed in 5-10% of patients. Overall, patients did not appear to have any significant growth retardation or delayed puberty. About two-thirds of patients required corticosteroid therapy and up to 25% were steroid dependent. An increased use of thiopurines was observed and the most recent data indicate that up to one-half of patients were exposed to thiopurines and 10-30% were exposed to anti-tumour necrosis factor. One-half of patients required hospitalisations and 20% of patients required colectomy after a follow-up of 10 years. Conclusions: Paediatric-onset UC is characterised by a high rate of disease extension. About 20% of patients had been operated at 10-year follow-up. New population-based studies are needed to evaluate the impact of new treatment strategies comprising immunosuppressants and biologics.
    Alimentary Pharmacology & Therapeutics 11/2015; DOI:10.1111/apt.13478 · 5.73 Impact Factor
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    ABSTRACT: The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) program was initiated by the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD). It examined potential treatment targets for inflammatory bowel disease (IBD) to be used for a "treat-to-target" clinical management strategy using an evidence-based expert consensus process. A Steering Committee of 28 IBD specialists developed recommendations based on a systematic literature review and expert opinion. Consensus was gained if ≥75% of participants scored the recommendation as 7-10 on a 10-point rating scale (where 10=agree completely). The group agreed upon 12 recommendations for ulcerative colitis (UC) and Crohn's disease (CD). The agreed target for UC was clinical/patient-reported outcome (PRO) remission (defined as resolution of rectal bleeding and diarrhea/altered bowel habit) and endoscopic remission (defined as a Mayo endoscopic subscore of 0-1). Histological remission was considered as an adjunctive goal. Clinical/PRO remission was also agreed upon as a target for CD and defined as resolution of abdominal pain and diarrhea/altered bowel habit; and endoscopic remission, defined as resolution of ulceration at ileocolonoscopy, or resolution of findings of inflammation on cross-sectional imaging in patients who cannot be adequately assessed with ileocolonoscopy. Biomarker remission (normal C-reactive protein (CRP) and calprotectin) was considered as an adjunctive target. Evidence- and consensus-based recommendations for selecting the goals for treat-to-target strategies in patients with IBD are made available. Prospective studies are needed to determine how these targets will change disease course and patients' quality of life.Am J Gastroenterol advance online publication, 25 August 2015; doi:10.1038/ajg.2015.233.
    The American Journal of Gastroenterology 08/2015; 110(9). DOI:10.1038/ajg.2015.233 · 10.76 Impact Factor
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    ABSTRACT: The incidence of thyroid cancers is increasing worldwide. Some somatic oncogene mutations (BRAF, NRAS, HRAS, KRAS) as well as gene translocations (RET/PTC, PAX8/PPAR-gamma) have been associated with the development of thyroid cancer. In our study, we analyzed these genetic alterations in 394 thyroid tissue samples (197 papillary carcinomas and 197 healthy). The somatic mutations and translocations were detected by Light Cycler melting method and Real-Time Polymerase Chain Reaction techniques, respectively. In tumorous samples, 86 BRAF (44.2 %), 5 NRAS (3.1 %), 2 HRAS (1.0 %) and 1 KRAS (0.5 %) mutations were found, as well as 9 RET/PTC1 (4.6 %) and 1 RET/PTC3 (0.5 %) translocations. No genetic alteration was seen in the non tumorous control thyroid tissues. No correlation was detected between the genetic variants and the pathological subtypes of papillary cancer as well as the severity of the disease. Our results are only partly concordant with the data found in the literature.
    Pathology & Oncology Research 08/2015; DOI:10.1007/s12253-015-9969-9 · 1.86 Impact Factor
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    ABSTRACT: To analyze the incidence and possible risk factors in hospitalized patients treated with Clostridium difficile infection (CDI). 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. 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. 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.
    World Journal of Gastroenterology 06/2015; 21(21):6728-35. DOI:10.3748/wjg.v21.i21.6728 · 2.37 Impact Factor
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    ABSTRACT: While bisphosphonates reduce fracture risk over 3 to 5 years, the optimal duration of treatment is uncertain. In a randomized extension study (E1) of the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly−Pivotal Fracture Trial (HORIZON−PFT), zoledronic acid (ZOL) 5 mg annually for 6 years showed maintenance of bone mineral density (BMD), decrease in morphometric vertebral fractures, and a modest reduction in bone turnover markers (BTMs) compared with discontinuation after 3 years. To investigate the longer-term efficacy and safety of ZOL, a second extension (E2) was conducted to 9 years in which women on ZOL for 6 years in E1 were randomized to either ZOL (Z9) or placebo (Z6P3) for 3 additional years. In this multicenter, randomized, double-blind study, 190 women were randomized to Z9 (n = 95) and Z6P3 (n = 95). The primary endpoint was change in total hip BMD at year 9 vs. year 6 in Z9 compared with Z6P3. Other secondary endpoints included fractures, BTMs, and safety. From year 6 to 9, the mean change in total hip BMD was −0.54% in Z9 vs. −1.31% in Z6P3 (difference 0.78%; 95% confidence interval [CI]: −0.37%, 1.93%; p = 0.183). BTMs showed small, non-significant increases in those who discontinued after 6 years compared with those who continued for 9 years. The number of fractures was low and did not significantly differ by treatment. While generally safe, there was a small increase in cardiac arrhythmias (combined serious and non-serious) in the Z9 group but no significant imbalance in other safety parameters. The results suggest almost all patients who have received six annual ZOL infusions can stop medication for up to 3 years with apparent maintenance of benefits. © 2015 American Society for Bone and Mineral Research.
    Journal of Bone and Mineral Research 05/2015; 30(5):934–944. DOI:10.1002/jbmr.2442 · 6.83 Impact Factor
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    ABSTRACT: Diagnostic delay is frequent in patients with Crohn's disease (CD), We developed a tool to predict early diagnosis. A systematic literature review and twelve CD specialists identified "Red Flags" symptoms or signs suggestive of CD. A 21-item questionnaire was administered to 36 healthy subjects and 80 patients with irritable bowel syndrome (non-CD group), and 85 patients with recently diagnosed CD (<18 months). Patients with CD were asked to recall symptoms and signs they experienced during the 12 months before diagnosis. Multiple logistic regression analyses selected and weighted independent items to construct the "Red Flags" index. ROC curve was used to assess the threshold that discriminated CD from non-CD. Association of the "Red Flags" index relative to this threshold was expressed through the odds-ratios (OR). 201 subjects, CD and non-CD, answered the questionnaire. The multivariate analysis identified 8 items independently associated with a diagnosis of CD. A minimum "Red Flags" index value of 8 was highly predictive of CD diagnosis with sensitivity and specificity bootstrap estimates of 0.94 (95% confidence interval: 0.88-0.99) and 0.94 (0.90-0.97), respectively. Positive and negative likelihood ratios were 15.1 (9.3-33.6) and 0.066 (0.013-0.125). The association between CD diagnosis and a "Red Flags" index value of 8 or more corresponds to an OR of 290 (p<0.0001). A "Red Flags" index, using early symptoms and signs, has a high predictive value for the diagnosis of CD. These results need prospective validation prior to introduction into clinical practice. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.
    Journal of Crohn s and Colitis 04/2015; 9(8). DOI:10.1093/ecco-jcc/jjv067 · 6.23 Impact Factor
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    ABSTRACT: Among their beneficial effects, non-steroidal anti-inflammatory drugs may also exert several side effects which depend on the dosage and the type of these medications. The most frequent gastrointestinal side effects usually develop shortly after the beginning of their administration, but others such as cardiovascular interactions (which are present much less frequently than gastrointestinal side effects) can also occur after the beginning of drug administration without a latency period. For a long-term treatment, non-steroidal anti-inflammatory drugs are most frequently used in the elderly population where patients typically have high cardiovascular risk and take other medicines, e.g. low dose acetylsalicylic acid that can interact with non-steroidal anti-inflammatory drugs; in this aspect diclofenac may cause less side effects. In this review, the authors briefly review cardiovascular side effects of non-steroidal anti-inflammatory drugs, the processes which potentially influence them, therapeutic consequences and their interaction with acetylsalicylic acid. Orv. Hetil., 2015, 156(13), 516-520.
    Orvosi Hetilap 03/2015; 156(13):516-520. DOI:10.1556/OH.2015.30120
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    ABSTRACT: Biological drugs opened up new horizons in the management of inflammatory bowel diseases (IBD). This study focuses on access to biological therapy in IBD patients across 9 selected Central and Eastern European (CEE) countries, namely Bulgaria, the Czech Republic, Estonia, Hungary, Latvia, Lithuania, Poland, Romania and Slovakia. Literature data on the epidemiology and disease burden of IBD in CEE countries was systematically reviewed. Moreover, we provide an estimation on prevalence of IBD as well as biological treatment rates. In all countries with the exception of Romania, lower biological treatment rates were observed in ulcerative colitis (UC) compared to Crohn's disease despite the higher prevalence of UC. Great heterogeneity (up to 96-fold) was found in access to biologicals across the CEE countries. Poland, Bulgaria, Romania and the Baltic States are lagging behind Hungary, Slovakia and the Czech Republic in their access to biologicals. Variations of reimbursement policy may be one of the factors explaining the differences to a certain extent in Bulgaria, Latvia, Lithuania, and Poland, but association with other possible determinants (differences in prevalence and incidence, price of biologicals, total expenditure on health, geographical access, and cost-effectiveness results) was not proven. We assume, nevertheless, that health deterioration linked to IBD might be valued differently against other systemic inflammatory conditions in distinct countries and which may contribute to the immense diversity in the utilization of biological drugs for IBD. In conclusion, access to biologicals varies widely among CEE countries and this difference cannot be explained by epidemiological factors, drug prices or total health expenditure. Changes in reimbursement policy could contribute to better access to biologicals in some countries.
    World Journal of Gastroenterology 02/2015; 21(6):1728-1737. DOI:10.3748/wjg.v21.i6.1728 · 2.37 Impact Factor
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    ABSTRACT: Objective: Primary hyperparathyroidism (PHPT) is diagnosed by the presence of hypercalcemia and elevated or non-suppressed parathyroid hormone (PTH) levels. Although surgery is usually curative, some individuals fail or are unable or unwilling to undergo parathyroidectomy. In such individuals, targeted medical therapy may be of value. Cinacalcet normalized calcium and lowered PTH in patients with PHPT in several phase 2 and open-label studies. We compared cinacalcet and placebo in subjects with PHPT unable to undergo parathyroidectomy. Design: Phase 3, double-blind, multi-centred, randomized, placebo-controlled study. Methods: Sixty-seven subjects (78% women) with moderate PHPT were randomized (1:1) to cinacalcet or placebo for ≤28 weeks. Main outcome measure: Achievement of a normal mean corrected total serum calcium concentration of ≤10.3 mg dl-1 (2.575 mmol l-1). Results: Baseline median (Q1, Q3) serum PTH was 164.0 (131.0, 211.0) pg ml-1 and mean (SD) serum Ca was 11.77 (0.46) mg dl-1. Serum Ca normalized (≤10.3 mg dl-1) in 75.8% of cinacalcet- vs. 0% placebo-treated subjects (p<0.001). Corrected serum Ca decreased by ≥1.0 mg dl-1 from baseline in 84.8% of cinacalcet- vs. 5.9% of placebo-treated subjects (p<0.001). Least squares mean (SEM) plasma PTH change from baseline was 23.80% (4.18%) (cinacalcet) vs. 1.01% (4.05%) (placebo) (p<0.001). Similar numbers of subjects in the cinacalcet and placebo groups reported adverse events (27 vs. 20) and serious adverse events (3 vs. 4). Most commonly reported AEs were nausea and muscle spasms. Conclusions: These results demonstrate that cinacalcet normalizes serum calcium in this PHPT population and appears to be well tolerated.
    European Journal of Endocrinology 01/2015; 172(5). DOI:10.1530/EJE-14-0877 · 4.07 Impact Factor
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    ABSTRACT: We developed a new IgA and IgG anti-MZGP2 antibody ELISA based on recombinant isoform-4 of human zymogen granule protein-2 (GP2), which is the major autoantigen of Crohn's disease (CrD)-specific pancreatic autoantibodies and assessed their clinical relevance in the largest inflammatory bowel disease (IBD) cohort tested to date. 832 sera were studied, including 617 consecutive IBD patients from 323 CrD and 294 ulcerative colitis (UC) followed-up in a tertiary centre, 112 pathological and 103 normal controls. Sensitivity of IgA anti-MZGP2 for CrD in the IBD population was 15% and specificity was 98%(95,99), while the sensitivity and specificity of IgG anti-MZGP2 was 27% and 97%. IgA and IgG anti-MZGP2 combined testing led to a sensitivity of 31% and specificity of 96%. Positivity for either ASCA (IgA or IgG) or anti-MZGP2 (IgA or IgG) showed a sensitivity of 75%(70,80) and specificity of 84%(79,89). IgA anti-MZGP2 antibodies were more prevalent in CrD patients with early disease onset (p=0.011). Also, anti-MZGP2 positive patients more frequently had extensive disease with ileal involvement. Patients with longer disease duration were more likely to have IgGanti-MZGP2 antibodies. Our novel ELISA confirms the high specificity of anti-MZGP2 antibodies for CrD and their association with disease severity phenotypes. Copyright © 2014. Published by Elsevier B.V.
    Clinica Chimica Acta 12/2014; 441. DOI:10.1016/j.cca.2014.12.010 · 2.82 Impact Factor
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    ABSTRACT: Background and aims: Combination therapy with infliximab and azathioprine has been shown to be superior to either treatment alone in Crohn's disease (CD). However, the benefit of combining adalimumab with an immunomodulator remains controversial. The aim of this study was to compare the efficacy of adalimumab monotherapy with combination therapy for induction and maintenance of response and remission in CD using a meta-analysis of the current literature. Methods: We performed a systematic literature search using Medline, Embase, Cochrane and several other databases. Prospective randomized controlled trials, retrospective cohort and case-controlled studies were included. The primary outcomes included induction of response and remission (up to week 12), maintenance of clinical response and remission (1 year) and the need for dose escalation. Several subgroup and sensitivity analyses were performed. Results: Eighteen out of 2743 retrieved studies were included. A meta-analysis of 7 studies assessing induction of remission (n = 1984) showed that ADA monotherapy was inferior to combination therapy [OR = 0.78 (0.64–0.96), p = 0.02]. A meta-analysis of 4 studies revealed that combination therapy was not statistically different from ADA for maintenance of remission [OR = 1.08 (0.79–1.48), p = 0.48]. Combination therapy was also not different from ADA monotherapy in terms of requirement for dose escalation [OR = 1.13 (0.69–1.85), p = 0.62]. Conclusions: Combination therapy with ADA and immunomodulator was mildly superior to ADA monotherapy for induction of remission in CD. The rate of remission at 1 year and the need for dose escalation were similar in both groups. These findings should be interpreted with caution in view of possible confounders and should be further validated by randomized controlled trials.
    Journal of Crohn s and Colitis 12/2014; 8(12). DOI:10.1016/j.crohns.2014.07.003 · 6.23 Impact Factor
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    ABSTRACT: No direct comparison of health care cost in patients with inflammatory bowel disease across the European continent exists. The aim of this study was to assess the costs of investigations and treatment for diagnostics and during the first year after diagnosis in Europe. The EpiCom cohort is a prospective population-based inception cohort of unselected inflammatory bowel disease patients from 31 Western and Eastern European centers. Patients were followed every third month from diagnosis, and clinical data regarding treatment and investigations were collected. Costs were calculated in euros (&OV0556;) using the Danish Health Costs Register. One thousand three hundred sixty-seven patients were followed, 710 with ulcerative colitis, 509 with Crohn's disease, and 148 with inflammatory bowel disease unclassified. Total expenditure for the cohort was &OV0556;5,408,174 (investigations: &OV0556;2,042,990 [38%], surgery: &OV0556;1,427,648 [26%], biologicals: &OV0556;781,089 [14%], and standard treatment: &OV0556;1,156,520 [22%)]). Mean crude expenditure per patient in Western Europe (Eastern Europe) with Crohn's disease: investigations &OV0556;1803 (&OV0556;2160) (P = 0.44), surgery &OV0556;11,489 (&OV0556;13,973) (P = 0.14), standard treatment &OV0556;1027 (&OV0556;824) (P = 0.51), and biologicals &OV0556;7376 (&OV0556;8307) (P = 0.31). Mean crude expenditure per patient in Western Europe (Eastern Europe) with ulcerative colitis: investigations &OV0556;1189 (&OV0556;1518) (P < 0.01), surgery &OV0556;18,414 (&OV0556;12,395) (P = 0.18), standard treatment &OV0556;896 (&OV0556;798) (P < 0.05), and biologicals &OV0556;5681 (&OV0556;72) (P = 0.51). In this population-based unselected cohort, costs during the first year of disease were mainly incurred by investigative procedures and surgeries. However, biologicals accounted for >15% of costs. Long-term follow-up of the cohort is needed to assess the cost-effectiveness of biological agents.
    Inflammatory Bowel Diseases 11/2014; 21(1). DOI:10.1097/MIB.0000000000000250 · 4.46 Impact Factor
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    ABSTRACT: Objective: Influenza vaccination is recommended for inflammatory bowel disease (IBD) patients on immunosuppressive therapy. The objective was to evaluate the antibody and cell-mediated immune response to the split and whole virion influenza vaccine in patients with IBD treated with anti-TNF-α and immunosuppressive therapy. Patients and methods: One hundred and fifty-six immunocompromised IBD patients were vaccinated. Fifty-three patients (control group) refused vaccination. Split virion vaccine and whole virion vaccine were used. Serum samples were obtained for pre- and postimmunization antibody titers to influenza vaccine (A/California/7/2009 [H1N1], A/Victoria/361/2011 [H3N2], B/Wisconsin/1/2010-like B/Hubei-Wujiagang/158/2009). Cell-mediated response was evaluated using an interferon (INF)-γ, interleukine (IL)-2 and tumor necrosis factor (TNF)-α ELISA. Results: Postimmunization titers of both influenza subtypes increased significantly after the administration of split virion vaccines compared to the controls and to those who received whole virion vaccine. The antibody titers of Influenza B also increased significantly in patients immunized with split vaccine and treated with anti-TNF-α therapy. After influenza vaccination, the level of serum IL-2 significantly decreased. No serious side effects developed occurred after influenza vaccination, and the influenza-like symptoms did not differ significantly between vaccinated versus control patients. The relapse of the disease was observed in only 10% of the patients and was more common in vaccinated than in control subjects. Conclusion: Split virion vaccines seem to be more effective than whole virion vaccines. Measuring the antibody responses is worthwhile in patients treated with immunosuppressants to determine the efficacy of influenza vaccination.
    Scandinavian Journal of Gastroenterology 11/2014; 50(2). DOI:10.3109/00365521.2014.928902 · 2.36 Impact Factor
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    ABSTRACT: Current data indicate a change in the epidemiology of inflammatory bowel diseases. The disease has become more widespread and the rise in the incidence has been reported in all age groups including early childhood and according to recent data also the elderly population. Some earlier studies have suggested that the phenotype and natural history of the disease may be different according to age of onset. Recently the importance of age at onset was reported in two population-based studies from France and Hungary including both paediatric and adult onset inception cohorts. Early onset disease was associated with more frequent disease extension in both Crohn’s disease and ulcerative colitis and in most but not all studies with higher frequency of complicated disease behaviour. This is also accompanied by striking differences in the medical management with earlier and more prevalent (2–3-fold) use of immunosuppressives and to some extent biologicals in patients with early compared to elderly-onset disease, especially in Crohn’s disease. However, the results of population-based studies on impact of age on surgery rates in Crohn´s disease as well as ulcerative colitis are conflicting. Furthermore, published data indicate that relative but not absolute risk of developing cancer and mortality is higher in patients with an early onset disease. Critical reviews that focus on the importance of age at onset in inflammatory bowel disease are rare. Therefore, the aim of this review is to describe the differences in epidemiology, clinical characteristics, and natural history of paediatric and elderly-onset inflammatory bowel disease based on studies performed in general population.
    Journal of Crohn s and Colitis 11/2014; 8(11). DOI:10.1016/j.crohns.2014.05.006 · 6.23 Impact Factor
  • Peter Laszlo Lakatos · Johan Burisch ·

    Gut 10/2014; 64(7). DOI:10.1136/gutjnl-2014-308460 · 14.66 Impact Factor
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    ABSTRACT: Objective: The aims of the present study were to examine gene and protein expression of the vitamin D-inactivating 24-hyroxylase (CYP24A1) and the activating 1-alpha-hydroxylase (CYP27B1) enzyme in human papillary thyroid cancer (PTC), furthermore, to investigate the association between CYP24A1 expression and numerous clinical, histological parameters and somatic oncogene mutation status of thyroid tumor tissues. Materials and methods: Gene expression analysis was carried out in 100 Hungarian thyroid samples, both normal and papillary tumor tissue sections of the same patient. The specific mRNA to the selected genes was analyzed by TaqMan probe-based quantitative real-time RT-PCR. The somatic oncogene mutation states of BRAF, NRAS, HRAS and KRAS were also tested. Results: CYP24A1 mRNA expression was markedly increased in 52 cases (52 %) of the examined papillary cancers compared with that of normal thyroid tissue. There was a tendency toward difference in the distribution of high-level CYP24A1 in the PTC accompanied with somatic oncogene mutation. Positive correlation was seen between increased CYP24A1 expression rate and a group of variables reflecting tumor malignity (mainly vascular invasion, lymph node metastasis, tumor size, hypothyreosis) by principal components analysis. No significant alteration was seen in CYP27B1 gene expression between neoplastic and normal tissues. Conclusions: A definite alteration was seen in vitamin D3-inactivating CYP24A1 gene activity in PTC compared to their normal tissues on a relatively large patient population. Our findings raise the possibility that CYP24A1 may also directly be involved in thyroid carcinogenesis.
    Journal of endocrinological investigation 09/2014; 38(3). DOI:10.1007/s40618-014-0165-7 · 1.45 Impact Factor
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    ABSTRACT: 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.
    Digestive and Liver Disease 08/2014; 46(11). DOI:10.1016/j.dld.2014.07.168 · 2.96 Impact Factor
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    ABSTRACT: The FREEDOM study and its Extension provide long-term information about the effects of denosumab for the treatment of postmenopausal osteoporosis. Treatment for up to 8 years was associated with persistent reduction of bone turnover, continued increases in bone mineral density, low fracture incidence, and a favorable benefit/risk profile. This study aims to report the results through year 5 of the FREEDOM Extension study, representing up to 8 years of continued denosumab treatment in postmenopausal women with osteoporosis. Women who completed the 3-year FREEDOM study were eligible to enter the 7-year open-label FREEDOM Extension in which all participants are scheduled to receive denosumab, since placebo assignment was discontinued for ethical reasons. A total of 4550 women enrolled in the Extension (2343 long-term; 2207 cross-over). In this analysis, women in the long-term and cross-over groups received denosumab for up to 8 and 5 years, respectively. Throughout the Extension, sustained reduction of bone turnover markers (BTMs) was observed in both groups. In the long-term group, mean bone mineral density (BMD) continued to increase significantly at each time point measured, for cumulative 8-year gains of 18.4 and 8.3 % at the lumbar spine and total hip, respectively. In the cross-over group, mean BMD increased significantly from the Extension baseline for 5-year cumulative gains of 13.1 and 6.2 % at the lumbar spine and total hip, respectively. The yearly incidence of new vertebral and nonvertebral fractures remained low in both groups. The incidence of adverse and serious adverse events did not increase over time. Through Extension year 5, eight events of osteonecrosis of the jaw and two events of atypical femoral fracture were confirmed. Denosumab treatment for up to 8 years was associated with persistent reductions of BTMs, continued BMD gains, low fracture incidence, and a consistent safety profile.
    Annals of the Rheumatic Diseases 06/2014; 73(Suppl 2):761-761. DOI:10.1136/annrheumdis-2014-eular.1119 · 10.38 Impact Factor
  • Michael D Mandel · Pal Miheller · Katalin Müllner · Petra A Golovics · Peter Laszlo Lakatos ·
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    ABSTRACT: Crohn's disease (CD) is a progressive condition, with most patients developing a penetrating or stricturing phenotype over time. The introduction of anti-tumor necrosis factor (TNF) therapies over the past 10-15 years, which was supported by accumulating evidence both from trials and clinical practice, has led to a significant change in patient management, monitoring, and treatment algorithms. Anti-TNF therapy was demonstrated to be effective for both luminal and fistulizing disease. Regular therapy with both infliximab and adalimumab was shown to increase the likelihood of clinical remission and mucosal healing, as well as to reduce the need for surgery and hospitalization in both clinical trials and clinical practice, especially in patients with pediatric-onset CD, shorter disease duration, and when used in combination with immunosuppressives. This has led to new treatment goals and to the use of early aggressive medical therapy in a selected group of patients with a worse prognosis. Exploratory clinical trials are underway to determine if further optimization of therapies and treatment beyond clinical remission leads to superior disease outcomes. However, more long-term clinical data are needed to assess whether an early, aggressive therapeutic strategy employing anti-TNF, alone or in combination with biologicals, can further improve long-term disease outcomes in both pediatric patients and young adults. © 2014 S. Karger AG, Basel.
    Digestive Diseases 06/2014; 32(4):351-9. DOI:10.1159/000358135 · 2.18 Impact Factor
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    ABSTRACT: To assess work disability (WD) rates in an inflammatory bowel disease (IBD) cohort involving patients with Crohn's disease (CD) or ulcerative colitis (UC) cohort and to identify possible clinical or demographic factors associated with WD. To our knowledge, this is the first study from Eastern Europe that has estimated indirect costs in IBD. Data from 443 (M/F: 202/241, CD/UC: 260/183, mean age: 35.5 (CD) and 40.5 (UC) years, biological drug exposure 31.2/11.5 %) consecutive patients were included. WD data were collected by questionnaire and the work productivity and activity impairment instrument. Disability pension (DP) rates in the general population were retrieved from public databases. The overall DP rate in this IBD population was 32.3 %, with partial disability in 24.2 %. Of all DP events, 88.8 % were directly related to IBD. Overall, full DP was more prevalent in IBD (RR: 1.51, p < 0.001) and CD (RR: 1.74, p < 0.001) but not in UC compared to the general population and also in CD compared to UC (OR 1.57, p = 0.03). RR for full DP was increased only in young CD patients (RR<35 year olds: 9.4; RR36-40 year olds: 9.4 and 5.6, p < 0.01 for both). In CD, age group, previous surgery, disease duration, frequent relapses, and the presence of arthritis/arthralgia were associated with an increased risk for DP. Among employed patients, absenteeism and presenteeism was reported in of 25.9 and 60.3 % patients, respectively, leading to a 28 % loss of work productivity and a 32 % activity loss, and was associated with disease activity and age group. Average cost of productivity loss due to disability and sick leave with a human capital approach was 1,450 and 430 /patient/year in IBD, respectively (total productivity loss 1,880 /patient/year), the costs of presenteeism were 2,605 (SD = 2,770) and 2,410 (SD = 2,970) /patient/year in CD and UC, respectively. Risk of DP was highly increased in young CD patients (sixfold to ninefold). Previous surgery and presence of arthritis/arthralgia was identified as risk factors for DP. Work productivity is significantly impaired in IBD and is associated with high productivity loss.
    The European Journal of Health Economics 05/2014; 15(S1). DOI:10.1007/s10198-014-0603-7 · 2.10 Impact Factor

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  • 2015
    • Corvinus University of Budapest
      Budapeŝto, Budapest, Hungary
  • 1986-2015
    • Semmelweis University
      • First Department of Internal Medicine
      Budapeŝto, Budapest, Hungary
  • 2014
    • Indian Broiler (IB) Group India
      Bhānpuri, Chhattisgarh, India
  • 2012
    • Semmelweis University
      Budapeŝto, Budapest, Hungary
  • 2011
    • Capital Medical University
      • Liver Research Center
      Peping, Beijing, China
  • 2010
    • Szent László Hospital, Budapest
      Budapeŝto, Budapest, Hungary
    • The Hungarian National Blood Transfusion Service
      Budapeŝto, Budapest, Hungary
  • 2009-2010
    • University of Debrecen
      Debreczyn, Hajdú-Bihar, Hungary
    • KBC Zvezdara Belgrade
      Beograd, Central Serbia, Serbia
    • VU University Medical Center
      Amsterdamo, North Holland, Netherlands
    • University of Illinois at Chicago
      Chicago, Illinois, United States
  • 2008
    • University of Szeged
      • Department of Medical Microbiology and Immunbiology
      Algyő, Csongrád, Hungary
  • 2007
    • New Mexico Clinical Research and Osteoporosis Center
      Albuquerque, New Mexico, United States
  • 1999
    • Universitätsklinikum Erlangen
      Erlangen, Bavaria, Germany
  • 1993
    • Northwestern University
      Evanston, Illinois, United States