Markusovszky University Teaching Hospital

Szombathely, Hungary

Markusovszky University Teaching Hospital

Szombathely, Hungary

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Kalman B.,University of Pécs | Kalman B.,Markusovszky University Teaching Hospital
Neurologist | Year: 2017

Background: Neurology has been continuously transforming by the refinement of molecular diagnostics and the development of diseasemodi fying treatments. The discovery of new antibody markers has elucidated the pathogenesis, provided the means of diagnostics, and offered cure or treatment for several immune-mediated neurological and neuropsychiatric disorders. The identification of pathogenic and marker autoantibodies has also facilitated defining the associated phenotypic spectra and the overlap among the phenotypes linked to individual immune markers. Review Summary: This survey presents the list of currently known autoimmune encephalitis entities along with the associated marker autoantibodies, highlights the phenotypic and immune pathogenic relationships, calls attention to the recently described rare syndromes, discusses the biological significance of the autoantibodies and targeted molecules, points out the potential postinfectious origin of immune pathogenesis in several of the disorders, and directs the readers to the latest diagnostic guidelines as well as to the generally used treatment approaches. Conclusions and Future Directions: Owing to the successful and usually combined use of various methods to detect serum and cerebrospinal fluid autoantibodies on rodent brain sections, in primary neuronal cell culture, in immune precipitation, and cell-based assays, or in other antigen-specific immune assays (Western blot, enzymelinked immunosorbent assay, and radioimmune assay), the subgroup of antibody marker-negative autoimmune encephalopathy syndromes is contracting, whereas the numbers of entities within the overall group are expanding. Recognition of the correct diagnosis is becoming increasingly rewarding not only for neurologists, but also for pediatric neurologists and psychiatrists. © Copyright 2017 Wolters Kluwer Health, Inc. All rights reserved.


Patai A.,Markusovszky University Teaching Hospital | Solymosi N.,University of Veterinary Medicine | Mohacsi L.,Corvinus University of Budapest | Patai A.V.,Semmelweis University
Gastrointestinal Endoscopy | Year: 2017

Background and Aims: Diclofenac and indomethacin are the most studied drugs for preventing post-ERCP pancreatitis (PEP). However, there are no prospective, randomized multicenter trials with a sufficient number of patients for correct evaluation of their efficacy. Our aim was to evaluate all prospective trials published in full text that studied the efficacy of diclofenac or indomethacin and were controlled with placebo or non-treatment for the prevention of PEP in adult patients undergoing ERCP. Methods: Systematic search of databases (PubMed, Scopus, Web of Science, Cochrane) for relevant studies published from inception to 30 June 2016. Results: Our meta-analysis of 4741 patients from 17 trials showed that diclofenac or indomethacin significantly decreased the risk ratio (RR) of PEP to 0.60 (95% confidence interval [CI], 0.46-0.78; P = .0001), number needed to treat (NNT) was 20, and the reduction of RR of moderate to severe PEP was 0.64 (95% CI, 0.43-0.97; P = .0339). The efficacy of indomethacin compared with diclofenac was similar (P = .98). The efficacy of indomethacin or diclofenac did not differ according to timing (P = .99) or between patients with average-risk and high-risk for PEP (P = .6923). The effect of non-rectal administration of indomethacin or diclofenac was not significant (P = .1507), but the rectal route was very effective (P = .0005) with an NNT of 19. The administration of indomethacin or diclofenac was avoided in patients with renal failure. Substantial adverse events were not detected. Conclusions: The use of rectally administered diclofenac or indomethacin before or closely after ERCP is inexpensive and safe and is recommended in every patient (without renal failure) undergoing ERCP. (Registration number: CRD42016042726, http://www.crd.york.ac.uk/prospero/.). © 2017 American Society for Gastrointestinal Endoscopy.


PubMed | Semmelweis University, Bajcsy Hospital, Central Military Hospital, Markusovszky University Teaching Hospital and 6 more.
Type: | Journal: International journal of cardiology | Year: 2016

Data are limited on the real-life use of coronary intervention (PCI) and on its long-term efficacy and safety in elderly patients with acute myocardial infarction (AMI).Data from a nation-wide registry of patients treated due to an AMI event in centers of invasive cardiology were analyzed for the potential interaction of age on the utilization of invasive therapy and outcome. Follow-up data of consecutive patients between March 1, 2013, and March 1, 2014 were analyzed. Differences in the risk of all-cause death at 1year between patients undergoing PCI versus others receiving conservative treatment were determined from vital records and were compared with propensity score matching.A total of 8485 consecutive patients were enrolled at 19 centers. Sixty-three percent of the patients were male; the mean age was 65.112.4years. The proportion of STEMI cases was 51%. STEMI cases were treated with primary PCI in 91.0% while patients with NSTEACS underwent PCI in 71.0%. The age of patients was a significant determinant of deferring coronary angiography (Hazard ratio (HR): 0.524 95% confidence interval (CI) 0.47-0.59, p<0.001) and PCI (HR: 0.76 95% CI 0.73-0.80, p<0.001). One-year survival after PCI was significantly better both in the overall and in the propensity matched cohort (HR: 0.44 [95% CI: 0.39-0.49] and HR: 0.59 [95% CI: 0.50-0.69], p<0.001, both). This benefit remained consistent in age-dependent subgroup analyses.Coronary intervention is underused among the elderly despite the mortality benefit of interventional therapy in myocardial infarction that is consistent in all age groups.


Nagy A.,University of Pécs | Eder K.,Markusovszky University Teaching Hospital | Selak M.A.,University of Pennsylvania | Kalman B.,University of Pécs | Kalman B.,Markusovszky University Teaching Hospital
Brain Research | Year: 2015

Glioblastoma is the most aggressive form of gliomas and is associated with short survival. Recent advancements in molecular genetics resulted in the identification of glioma genomic, epigenomic and transcriptomic hallmarks, and multidimensional data allowed clustering of glioblastomas into molecular subtypes. Parallel with these developments, much scientific attention has been attracted by the exploration of two functional processes linked to mitochondrial regulation. One of these processes involves genomic and mitochondrial gene mutations, mitochondrial protein expression modifications and altered metabolic regulation that define glioblastoma. The second mitochondrially-centered process involves complex molecular interactions and pathways that influence the extrinsic or the intrinsic mechanisms of apoptosis regulation and may underlie the uncontrolled spreading, recurrence and drug resistance of glioblastoma. While the available data are not yet comprehensive, these two complex processes represent important aspects of tumor cell biology, which may provide complementary opportunities for therapeutic manipulations of this highly resistant tumor type. © 2014 Elsevier B.V.


Patai A.,Sopron Elizabeth Teaching Hospital | Patai A.,Markusovszky University Teaching Hospital | Solymosi N.,Eötvös Loránd University | Patai A.V.,Semmelweis University
Medicine (United States) | Year: 2014

Rectal indomethacin has been proven to be effective for prevention of post-ERCP pancreatitis (PEP) but its impact on bleeding after biliary sphincterotomy (BABES) and cardiovascular mortality has not been extensively studied. We aimed to assess the effect of indomethacin on the rate of BABES and short-term cardiovascular mortality, particularly in patients receiving antiplatelet therapy (APT). In this double-blind, randomized, placebo-controlled, single-center study, 100mg indomethacin or placebo was given within 1 hour before biliary endoscopic sphincterotomy to in-patients including those who are receiving APT (acetylsalicylic acid [ASA] and/or clopidogrel). Cardiovascular mortality and BABES were observed for 30 days. Of 576 randomized patients (289 indomethacin, 287 placebo), 87 patients used 100mg/day ASA and 29 patients took 75mg/day clopidogrel, among them 5 patients were on dual APT. The ASA and clopidogrel taking patients were older than patients without APT (P<0.001), but these groups were similar in other parameters. BABES occurred similarly in different subgroups: indomethacin (8.0%) vs placebo (9.4%) (P=0.56), ASA (10.3%) vs non-ASA (8.4%) (P=0.54), clopidogrel (6.9%) vs nonclopidogrel (8.8%) (P>0.99). No BABES was observed among patients on dual APT. There was no difference in cardiovascular mortality between subgroups (P>0.99). Results indicate that single dose of 100mg indomethacin does not increase BABES rate and cardiovascular mortality. This result is independent from administering antiplatelet agents.


Eder K.,Markusovszky University Teaching Hospital | Kalman B.,Markusovszky University Teaching Hospital | Kalman B.,University of Pécs
Pathology & Oncology Research | Year: 2014

Glioblastoma is the most common intracranial malignancy and constitutes about 50 % of all gliomas. Both inter-tumor and intra-tumor histological heterogeneity had been recognized by the early 1980-ies. Recent works using novel molecular platforms provided molecular definitions of these tumors. Based on comprehensive genomic sequence analyses, The Cancer Genome Atlas Research Network (TCGA) cataloged somatic mutations and recurrent copy number alterations in glioblastoma. Robust transcriptome and epigenome studies also revealed inter-tumor heterogeneity. Integration and cluster analyses of multi-dimensional genomic data lead to a new classification of glioblastoma tumors into subtypes with distinct biological features and clinical correlates. However, multiple observations also revealed tumor area-specific patterns of genomic imbalance. In addition, genetic alterations have been identified that were common to all areas analyzed and other alterations that were area specific. Analyses of intra-tumor transcriptome variations revealed that in more than half of the examined cases, fragments from the same tumor mass could be classified into at least two different glioblastoma molecular subgroups. Intra-tumor heterogeneity of molecular genetic profiles in glioblastoma may explain the difficulties encountered in the validation of oncologic biomarkers, and contribute to a biased selection of patients for single target therapies, treatment failure or drug resistance. In this paper, we summarize the currently available literature concerning inter- and intra-tumor molecular heterogeneity of glioblastomas, and call attention to the importance of this topic in relation to the growing efforts in routine molecular diagnostics and personalized therapy. © 2014 Arányi Lajos Foundation.


Plander M.,Markusovszky University Teaching Hospital | Kalman B.,Markusovszky University Teaching Hospital | Kalman B.,University of Pécs
Autoimmunity | Year: 2016

Autoimmune diseases represent a heterogeneous group of common disorders defined by complex trait genetics and environmental effects. The genetic variants usually align in immune and metabolic pathways that affect cell survival or apoptosis and modulate leukocyte function. Nevertheless, the exact triggers of disease development remain poorly understood and the current therapeutic interventions only modify the disease course. Both the prevention and the cure of autoimmune disorders are beyond our present medical capabilities. In contrast, a growing number of single gene autoimmune disorders have also been identified and characterized in the last few decades. Mutations and other gene alterations exert significant effects in these conditions, and often affect genes involved in central or peripheral immunologic tolerance induction. Even though a single genetic abnormality may be the disease trigger, it usually upsets a number of interactions among immune cells, and the biological developments of these monogenic disorders are also complex. Nevertheless, identification of the triggering molecular abnormalities greatly contributes to our understanding of the pathogenesis of autoimmunity and facilitates the development of newer and more effective treatment strategies. © 2016 Informa UK Limited, trading as Taylor & Francis Group.


Eder K.,Markusovszky University Teaching Hospital | Kalman B.,Markusovszky University Teaching Hospital | Kalman B.,University of Pécs
NeuroMolecular Medicine | Year: 2015

Glioblastoma is the most common intracranial malignancy that constitutes about 50 % of all gliomas. Despite aggressive, multimodal therapy consisting of surgery, radiation, and chemotherapy, the outcome of patients with glioblastoma remains poor with 5-year survival rates of <10 %. Resistance to conventional therapies is most likely caused by several factors. Alterations in the functions of local immune mediators may represent a critical contributor to this resistance. The tumor microenvironment contains innate and adaptive immune cells in addition to the cancer cells and their surrounding stroma. These various cells communicate with each other by means of direct cell–cell contact or by soluble factors including cytokines and chemokines, and act in autocrine and paracrine manners to modulate tumor growth. There are dynamic interactions among the local immune elements and the tumor cells, where primarily the protective immune cells attempt to overcome the malignant cells. However, by developing somatic mutations and epigenetic modifications, the glioblastoma tumor cells acquire the capability of counteracting the local immune responses, and even exploit the immune cells and products for their own growth benefits. In this review, we survey those immune mechanisms that likely contribute to glioblastoma pathogenesis and may serve as a basis for novel treatment strategies. © 2015, Springer Science+Business Media New York.


PubMed | Hungarian Academy of Sciences, Markusovszky University Teaching Hospital and Semmelweis University
Type: | Journal: Pathology oncology research : POR | Year: 2016

Colorectal sessile serrated adenomas (SSA) are hypothesized to be precursor lesions of an alternative, serrated pathway of colorectal cancer, abundant in genes with aberrant promoter DNA hypermethylation. In our present pilot study, we explored DNA methylation profiles and examined selected gene mutations in SSA. Biopsy samples from patients undergoing screening colonoscopy were obtained during endoscopic examination. After DNA isolation and quality analysis, SSAs (n=4) and healthy controls (n=5) were chosen for further analysis. DNA methylation status of 96 candidate genes was screened by q(RT)PCR using Methyl-Profiler PCR array system. Amplicons for 12 gene mutations were sequenced by GS Junior Instrument using ligated and barcoded adaptors. Analysis of DNA methylation revealed 9 hypermethylated genes in both normal and SSA samples. 12 genes (CALCA, DKK2, GALR2, OPCML, PCDH10, SFRP1, SFRP2, SLIT3, SST, TAC1, VIM, WIF1) were hypermethylated in all SSAs and 2 additional genes (BNC1 and PDLIM4) were hypermethylated in 3 out of 4 SSAs, but in none of the normal samples. 2 SSAs exhibited BRAF mutation and synchronous MLH1 hypermethylation and were microsatellite instable by immunohistochemical analysis. Our combined mutation and DNA methylation analysis revealed that there is a common DNA methylation signature present in pre-neoplastic SSAs. This study advocates for the use of DNA methylation as a potential biomarker for the detection of SSA; however, further investigation is needed to better characterize the molecular background of these newly recognized colorectal lesions.


Patai A,Markusovszky University Teaching Hospital | Solymosi N.,Markusovszky University Teaching Hospital | Patai A.V.,Markusovszky University Teaching Hospital
Medicine | Year: 2014

Rectal indomethacin has been proven to be effective for prevention of post-ERCP pancreatitis (PEP) but its impact on bleeding after biliary sphincterotomy (BABES) and cardiovascular mortality has not been extensively studied. We aimed to assess the effect of indomethacin on the rate of BABES and short-term cardiovascular mortality, particularly in patients receiving antiplatelet therapy (APT).In this double-blind, randomized, placebo-controlled, single-center study, 100 mg indomethacin or placebo was given within 1 hour before biliary endoscopic sphincterotomy to in-patients including those who are receiving APT (acetylsalicylic acid [ASA] and/or clopidogrel). Cardiovascular mortality and BABES were observed for 30 days.Of 576 randomized patients (289 indomethacin, 287 placebo), 87 patients used 100 mg/day ASA and 29 patients took 75 mg/day clopidogrel, among them 5 patients were on dual APT. The ASA and clopidogrel taking patients were older than patients without APT (P < 0.001), but these groups were similar in other parameters. BABES occurred similarly in different subgroups: indomethacin (8.0%) vs placebo (9.4%) (P = 0.56), ASA (10.3%) vs non-ASA (8.4%) (P = 0.54), clopidogrel (6.9%) vs nonclopidogrel (8.8%) (P > 0.99). No BABES was observed among patients on dual APT. There was no difference in cardiovascular mortality between subgroups (P > 0.99).Results indicate that single dose of 100 mg indomethacin does not increase BABES rate and cardiovascular mortality. This result is independent from administering antiplatelet agents.

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