Markusovszky Teaching Hospital

Szombathely, Hungary

Markusovszky Teaching Hospital

Szombathely, Hungary
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Murnyak B.,Debrecen University | Kouhsari M.C.,Debrecen University | Hershkovitch R.,Debrecen University | Kalman B.,University of Pécs | And 5 more authors.
Oncotarget | Year: 2017

Overexpression of PARP1 exists in various cancers, including glioblastoma (GBM). Although PARP1 inhibition is a promising therapeutic target, no comprehensive study has addressed PARP1's expression characteristics and prognostic role regarding molecular heterogeneity in astrocytomas including GBM. Our aim was to evaluate PARP1's associations with survival, WHO grade, lineage specific markers, and GBM transcriptomic subtypes. We collected genomic and clinical data from the latest glioma datasets of The Cancer Genome Atlas and performed PARP1, ATRX, IDH1, and p53 immunohistochemistry on GBM tissue samples. We demonstrated that PARP1 gain and increased mRNA expression are characteristics of high-grade astrocytomas, particularly of Proneural and Classical GBM subtypes. Additionally, higher PARP1 levels exhibited an inverse correlation with patient survival (p < 0.005) in the Classical subgroup. ATRX (p=0.006), and TP53 (p=0.015) mutations were associated with increased PARP1 expression and PARP1 protein level correlated with ATRX loss and p53 overexpression. Furthermore, higher PARP1 expression together with wildtype TP53 indicated shorter survival (p=0.039). Therefore, due to subtype specificity, PARP1 expression level and TP53 mutation status are reliable marker candidates to distinguish Proneural and Classical subtypes, with prognostic and therapeutic implications in GBM. © Murnyák et al.


Szots M.,Mor Kaposi General Hospital | Marton A.,Mor Kaposi General Hospital | Kiss T.,Markusovszky Teaching Hospital | Berki T.,University of Pécs | And 2 more authors.
Journal of the Neurological Sciences | Year: 2014

Antibodies against LGI1 (leucin-rich glioma-inactivated 1 protein) are associated with limbic encephalitis (LE), which is characterized by a favorable outcome following immunotherapy. Here, we present two cases, where antibodies against LGI1 were detected in the sera 36 and 53 months after acute LE, respectively, and none of the patients received immunotherapy. LE showed characteristics of LGI1 encephalitis in both cases, including low sodium content in the sera; disorientation, hallucination, short-term memory loss; and epileptic seizures. One patient had faciobrachial tonic seizures. MRI indicated bilateral inflammation of the hippocampus in one case. We reviewed longitudinal clinical and MRI data covering 53 and 36 months after LE without immunotherapy, respectively. Both patients became seizure-free and spontaneously recovered with mild/moderate cognitive impairment. No relapses have been observed. Follow-up brain MRI indicated early hippocampal sclerosis and global brain atrophy in one case characterized by more pronounced cognitive deficit. Memory and verbal fluency were affected most during the natural course of LGI1 encephalitis. LGI1 encephalitis had a monophasic course and spontaneously improved, suggesting that a relatively benign natural course may contribute to the favorable outcome observed after immunotherapy. Our data also indicate that LGI1 antibodies can be present in the sera without clinical disease activity. © 2014 Elsevier B.V.


PubMed | Markusovszky Teaching Hospital, University of Pécs, Mor Kaposi General Hospital and University of Southern Denmark
Type: Case Reports | Journal: Journal of the neurological sciences | Year: 2014

Antibodies against LGI1 (leucin-rich glioma-inactivated 1 protein) are associated with limbic encephalitis (LE), which is characterized by a favorable outcome following immunotherapy. Here, we present two cases, where antibodies against LGI1 were detected in the sera 36 and 53 months after acute LE, respectively, and none of the patients received immunotherapy. LE showed characteristics of LGI1 encephalitis in both cases, including low sodium content in the sera; disorientation, hallucination, short-term memory loss; and epileptic seizures. One patient had faciobrachial tonic seizures. MRI indicated bilateral inflammation of the hippocampus in one case. We reviewed longitudinal clinical and MRI data covering 53 and 36 months after LE without immunotherapy, respectively. Both patients became seizure-free and spontaneously recovered with mild/moderate cognitive impairment. No relapses have been observed. Follow-up brain MRI indicated early hippocampal sclerosis and global brain atrophy in one case characterized by more pronounced cognitive deficit. Memory and verbal fluency were affected most during the natural course of LGI1 encephalitis. LGI1 encephalitis had a monophasic course and spontaneously improved, suggesting that a relatively benign natural course may contribute to the favorable outcome observed after immunotherapy. Our data also indicate that LGI1 antibodies can be present in the sera without clinical disease activity.


PubMed | Markusovszky Teaching Hospital, Arkhangelsk Clinical Oncology Dispensary, National Taiwan University Hospital, Orszagos Koranyi TBC es Pulmonologiai Intezet and 4 more.
Type: Clinical Trial, Phase II | Journal: Lung cancer (Amsterdam, Netherlands) | Year: 2014

ABIGAIL, a phase II, randomized, open-label, multicenter study evaluated the correlation between biomarkers and best overall response (BOR) to bevacizumab with chemotherapy in patients with advanced or recurrent non-small-cell lung cancer (NSCLC). Exploratory analyses of vascular endothelial growth factor (VEGF) clinical genotyping data are presented.A total of 303 patients with NSCLC were randomized to receive bevacizumab 7.5mg/kg or 15mg/kg until progression or unacceptable toxicity (plus six cycles of chemotherapy). Patients provided blood samples for biomarker analysis. Exploratory analyses were conducted to assess whether genetic variants in VEGF-A or VEGFR-1/-2 act as efficacy or safety biomarkers. Single nucleotide polymorphisms (SNPs) were determined using individual genotyping assays. DNA analysis for 12 SNPs across three genes is reported: VEGF-A (five SNPs), VEGFR-1 (three SNPs), and VEGFR-2 (four SNPs).c.+405/c.-634 (CG), VEGF-A: c.-460 >C; c-1498 >C (CT), andc.-2578 C>A were associated with >50% higher odds of responding to treatment. VEGFR-1: rs9554316 (GT) was associated with >30% higher risk of progression and >40% higher risk of death.c.+936 C>T was associated with higher incidence of hypertension.Four genetic variants of VEGF-A and VEGFR-1 were associated with bevacizumab treatment outcome. Three variants in VEGF-A were associated with increased BOR, one variant in VEGFR-1 was associated with worse progression-free survival/overall survival. These associations were not statistically significant after correction for multiple testing. No genetic variant was associated with significantly higher risk of hypertension. Replication in additional studies may provide insight into the use of these variants to predict response to bevacizumab.


Dobronte Z.,Markusovszky Teaching Hospital | Szepes Z.,University of Szeged | Izbeki F.,Szent Gyorgy Regional Hospital | Gervain J.,Szent Gyorgy Regional Hospital | And 7 more authors.
World Journal of Gastroenterology | Year: 2014

AIM: To investigate the effectiveness of rectally administered indomethacin in the prophylaxis of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis and hyperamylasaemia in a multicentre study. METHODS: A prospective, randomised, placebo-controlled multicentre study in five endoscopic units was conducted on 686 patients randomised to receive a suppository containing 100 mg indomethacin, or an inert placebo, 10-15 min before ERCP. Post-ERCP pancreatitis and hyperamylasaemia were evaluated 24 h following the procedure on the basis of clinical signs and laboratory parameters, and computed tomography/magnetic resonance imaging findings if required. RESULTS: Twenty-one patients were excluded because of incompleteness of their data or because of protocol violation. The results of 665 investigations were evaluated: 347 in the indomethacin group and 318 in the placebo group. The distributions of the risk factors in the two groups did not differ significantly. Pancreatitis developed in 42 patients (6.3%): it was mild in 34 (5.1%) and severe in eight (1.2%) cases. Hyperamylaesemia occurred in 160 patients (24.1%). There was no significant difference between the indomethacin and placebo groups in the incidence of either post-ERCP pancreatitis (5.8% vs 6.9%) or hyperamylasaemia (23.3% vs 24.8%). Similarly, subgroup analysis did not reveal any significant differences between the two groups. CONCLUSION: 100 mg rectal indomethacin administered before ERCP did not prove effective in preventing post-ERCP pancreatitis. © 2014 Baishideng Publishing Group Inc. All rights reserved.


Horvath B.,Markusovszky Teaching Hospital | Horvath B.,University of Pécs | Lakatos F.,Hungary National Public Health and Medical Officer Service Ltd | Toth C.,Markusovszky Teaching Hospital | And 2 more authors.
Journal of Perinatal Medicine | Year: 2014

Objective: To assess neonatal outcomes and associated findings in pregnant women identified after delivery as having had underlying subclinical chorioamnionitis by either histology or bacterial culture. Methods: In 16 years, 8974 clinical, histological, and bacterial culture data were obtained retrospectively. Results: Placental histology was analyzed in 4237 pregnancies (2785 term and 1452 preterm) and 4737 amniotic cavity cultures were obtained during 5446 cesarean deliveries (3268 term and 1469 preterm). Histological results and bacterial cultures were both available in 1270 of the preterm deliveries. Histology revealed inflammation, suggestive of infection, in 13.6% of placentas. Subclinical acute chorioamnionic inflammation was confirmed in 142 out of 2785 term pregnancies (5.1%) and in 436 out of 1452 preterm pregnancies (30.0%, P < 0.001). Bacteriological culture of the intrauterine cavity was obtained from the lower uterine segment of the uterus during cesarean section. A positive culture was found in 19.9% of all cases (941/4737), this proportion was significantly higher in preterm deliveries (343/1273, 26.9%) than in term (17.3%, P < 0.001). The lower the birth-weight or gestational age, the higher the frequency of silent infections in the uterine cavity. Conclusions: Our study findings support the association between intra-amniotic infections and preterm delivery.


Horvath B.,University of Pécs | Horvath B.,Markusovszky Teaching Hospital | Bodecs T.,University of Pécs | Boncz I.,University of Pécs | Bodis J.,University of Pécs
Metabolic Syndrome and Related Disorders | Year: 2013

Background: The aim of our study was to elucidate the association of the metabolic syndrome with the risk of unsuccessful pregnancy. Methods: This was a retrospective observational study conducted at Markusovszky Teaching Hospital, Szombathely, Hungary, a tertiary health care center. During the study period of 2007-2011 (5 years), 7373 pregnancies were followed. Pregnant women who were suffering from metabolic syndrome in the first trimester of gestation during the study period were compared to all other pregnant women without the syndrome. Retrospectively, 219 (2.9%) patients met the criteria of metabolic syndrome during the first trimester. Our goal was to evaluate the prevalence of the metabolic syndrome in normal pregnancies and in those complicated by either premature birth, or intrauterine growth retardation (IUGR), pregnancy-induced hypertension, and preeclampsia. Results: The rate of preterm birth was 15.2% [32/219 in the metabolic syndrome group vs. 11.1% (p=0.051) in the control group]. Within the affected group, 40 pregnancies were complicated with IUGR (18.4%) versus 3.3%, in the unaffected group (p<0.001). In 58 cases, we observed preeclampsia during pregnancy [26.7% vs. 5.2% (p<0.001)] in the control group. Among the patients affected by the metabolic syndrome, 83 patients (38.2%) had more then one pregnancy complication during pregnancy, and only 59 cases (27.2%) had no adverse events during pregnancy and delivery (p<0.001). Conclusions: Our study demonstrated a higher rate of complicated pregnancies in association with metabolic syndrome compared to the control group. © Copyright 2013, Mary Ann Liebert, Inc.


Csakvary V.,Markusovszky Teaching Hospital | Puskas T.,Markusovszky Teaching Hospital | Oroszlan G.,Markusovszky Teaching Hospital | Lakatos P.,Semmelweis University | And 4 more authors.
Bone | Year: 2013

Background: The conditions that define bone development in prepuberty profoundly influence bone health later in life. We aimed to reveal important determinants of bone mass in Tanner stage I. Methods: We studied 84 healthy children (43 girls and 41 boys) aged 7 to 11. years. Serum estradiol (E2), 25-hydroxyvitamin D3-vitamin [25(OH)D3], intact parathyroid hormone (PTHi), osteocalcin (OC) and β-crosslaps (CTXs) were longitudinally analyzed (Roche Diagnostics System). Total and spine bone mineral content (tBMC and LBMC) and density (tBMD and LBMD) were assessed, and total fat body mass index (FBMi) was calculated (DXA Lunar Prodigy). Results: The serum PTHi, OC and LBMD values were significantly higher in girls than in boys. The mean 25(OH)D3 level was lower but not significantly in girls compared to boys. Significant negative correlation was found between PTHi and 25(OH)D3 levels (r=-0.28; p=0.011) when tested in all subjects, but no correlation was detected when the gender groups were separately tested. There was a trend for higher E2 levels in girls. Significant positive correlation (r=0.32; p=0.042) was detected between FBMi and E2 concentration in girls only. A significant negative correlation was found between E2 and 25(OH)D3 levels (r=-0.37, p<0.05) in girls with elevated (>3.6pmol/l) PTHi and with suboptimal (<75nmol/l) 25(OH)D3 levels. Furthermore, positive correlations were noted between E2 and CTXs and OC (r=0.54, p<0.01 and r=0.39, p<0.03) and a marginally significant positive correlation (r=0.33; p=0.06) was detected between OC and PTHi levels in girls. However, we detected no correlations when these markers were analyzed in boys. There was a significant correlation between E2 and all BMC and LBMD values in both genders. The tBMD, LBMD and tBMC values showed weak, but significant negative associations with 25OHD3 levels (β=-0.44 to -0.55; p<0.001) in girls only. All BMD and BMC values were positively predicted by OC levels, but not by CTXs, in both genders. Among the biochemical markers, E2 was the only factor correlating with all dependent variables (BMCs and BMDs) in both genders. Among all parameters analyzed, FBMi (β=0.64) showed the strongest influence on tBMC characteristically in girls only. Conclusions: Our results support that 1.) E2 levels play a key role in defining bone turnover and bone mass in both genders already in prepuberty; 2.) high PTHi levels in childhood should be evaluated with caution, because the normal range for serum PTHi in different Tanner stage groups is not well established; and 3.) the negative correlation between 25(OH)D and E2 and the positive correlation between PTHi and OC suggest that estrogens regulate PTHi indirectly and cause lower circulating 25(OH)D3 levels. We propose that the decreased levels of 25(OH)D3 reflect not the real vitamin supply, but may rather be the result of E2 regulation. Therefore, the actual serum 25OHD levels may underestimate the availability of factors supporting bone formation. © 2013 Elsevier Inc..


Horvath B.,University of Pécs | Horvath B.,Markusovszky Teaching Hospital | Grasselly M.,Markusovszky Teaching Hospital | Bodecs T.,University of Pécs | And 2 more authors.
International Journal of Gynecology and Obstetrics | Year: 2013

Objective To assess the benefits of a chemoprophylaxis program based on screening women for group B streptococcus (GBS) infection between 30 and 32 weeks of pregnancy in a population with a high rate of premature births. Methods From 1995 to 2011, 24 950 women were screened for GBS infection between 30 and 32 weeks of pregnancy at Markusovszky Teaching Hospital, Szombathely, Hungary. Those who tested positive, and those who tested negative but were at risk of infecting their newborns, underwent intrapartum prophylaxis. Neonatal outcomes were compared with those of a historical cohort that underwent no screening or treatment, and with those published in CDC/ACOG guidelines recommending screening closer to term. Results There were 63 infected newborns (0.2%) in the study cohort, and 1 of 8 with sepsis died. There were 149 infected newborns (0.7%) in the historical cohort, and 29 of 31 with sepsis died. Conclusion Screening women early in a population with a high rate of premature births may simplify preterm labor management. It results, however, in a higher incidence of early onset neonatal GBS disease than when screening is done closer to term. © 2013 International Federation of Gynecology and Obstetrics.


PubMed | Markusovszky Teaching Hospital
Type: Journal Article | Journal: World journal of gastroenterology | Year: 2014

To investigate the effectiveness of rectally administered indomethacin in the prophylaxis of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis and hyperamylasaemia in a multicentre study.A prospective, randomised, placebo-controlled multicentre study in five endoscopic units was conducted on 686 patients randomised to receive a suppository containing 100 mg indomethacin, or an inert placebo, 10-15 min before ERCP. Post-ERCP pancreatitis and hyperamylasaemia were evaluated 24 h following the procedure on the basis of clinical signs and laboratory parameters, and computed tomography/magnetic resonance imaging findings if required.Twenty-one patients were excluded because of incompleteness of their data or because of protocol violation. The results of 665 investigations were evaluated: 347 in the indomethacin group and 318 in the placebo group. The distributions of the risk factors in the two groups did not differ significantly. Pancreatitis developed in 42 patients (6.3%): it was mild in 34 (5.1%) and severe in eight (1.2%) cases. Hyperamylaesemia occurred in 160 patients (24.1%). There was no significant difference between the indomethacin and placebo groups in the incidence of either post-ERCP pancreatitis (5.8% vs 6.9%) or hyperamylasaemia (23.3% vs 24.8%). Similarly, subgroup analysis did not reveal any significant differences between the two groups.100 mg rectal indomethacin administered before ERCP did not prove effective in preventing post-ERCP pancreatitis.

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