Publications by authors named "Thomas Szekeres"

Article Synopsis
  • Brain metastases (BM) are a critical issue for patients with HER2-positive metastatic breast cancer, necessitating better treatment options; the study examined the effectiveness of the antibody-drug conjugate trastuzumab deruxtecan (T-DXd) compared to trastuzumab emtansine.* -
  • In the TUXEDO-1 trial involving patients with HER2-positive BC and active BM, the results showed a median progression-free survival (PFS) of 21 months and an overall survival (OS) that had not been reached at 26.5 months of follow-up, indicating positive outcomes for T-DXd.* -
  • No new safety concerns emerged throughout the trial, with fatigue being the most reported
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Monitoring for thrombosis and hemolysis is crucial for patients under extracorporeal or mechanical circulatory support, but it can be costly. We investigated correlations between hemolysis index (HI) and plasma-free hemoglobin (PFH) levels on one hand, and between the HI and plasma lactate dehydrogenase (LDH) levels on the other, in critically ill patients with and without extracorporeal or mechanical circulatory support. Additionally, we calculated the cost reductions if monitoring through HI were to replace monitoring through PFH or plasma LDH.

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The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus has been causing the COVID-19 pandemic since December 2019, with over 600 million infected persons worldwide and over six million deaths. We investigated the anti-viral effects of polyphenolic green tea ingredients and the synthetic resveratrol analogue 3,3',4,4',5,5'-hexahydroxy--stilbene (), a compound with antioxidant, antitumor and anti-HIV properties. In the TCID assay, four out of nine green tea constituents showed minor to modest cell protective effects, whereas HHS demonstrated the highest reduction (1103-fold) of the TCID, indicating pronounced inhibition of virus replication.

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Background & Aims: Ammonia levels predicted hospitalisation in a recent landmark study not accounting for portal hypertension and systemic inflammation severity. We investigated (i) the prognostic value of venous ammonia levels (outcome cohort) for liver-related outcomes while accounting for these factors and (ii) its correlation with key disease-driving mechanisms (biomarker cohort).

Methods: (i) The outcome cohort included 549 clinically stable outpatients with evidence of advanced chronic liver disease.

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Background: High-sensitivity C-reactive protein (hs-CRP) is a biomarker used for risk prediction for cardiovascular disease by assessing low concentration of inflammation. Measurements of regular CRP have become very sensitive with a lower detection limit of 0.3 mg/L.

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Article Synopsis
  • - The TUXEDO-1 trial tested trastuzumab deruxtecan, an antibody-drug conjugate, on 15 patients with HER2-positive metastatic breast cancer and brain metastases, focusing on its ability to treat brain lesions.
  • - Results showed a significant intracranial response rate, with 73.3% of patients achieving a complete or partial response, which exceeded the trial's target of 61%.
  • - Safety was consistent with previous findings, and patients maintained their quality of life and cognitive function during treatment, suggesting trastuzumab deruxtecan could be a viable option for managing brain metastases in these patients.
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Article Synopsis
  • Pretransplant kidney graft biopsies can help assess the quality of deceased donor organs, but data on the role of donor proteinuria in this context was lacking.
  • A study of 147 kidney biopsies from 88 deceased donors showed a positive correlation between donor urinary protein to creatinine ratio (UPCR) and the severity of chronic lesions in the kidneys.
  • Findings suggest that as UPCR increases, the likelihood of more lesions in the kidney graft also increases, indicating that donor proteinuria could be a useful factor in evaluating organ quality before transplantation.
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(1) Background: Cirrhotic patients have an increased risk for severe COVID-19. We investigated the renin-angiotensin-aldosterone system (RAS), parameters of endothelial dysfunction, inflammation, and coagulation/fibrinolysis in cirrhotic patients and in COVID-19 patients. (2) Methods: 127 prospectively characterized cirrhotic patients (CIRR), along with nine patients with mild COVID-19 (mild-COVID), 11 patients with COVID-19 acute respiratory distress syndrome (ARDS; ARDS-COVID), and 10 healthy subjects (HS) were included in the study.

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Objectives: N-terminal pro-brain natriuretic peptide (NT-proBNP), a standard marker for diagnosis and treatment guidance of heart failure, has previously been investigated in high-risk patients undergoing cardiac and non-cardiac surgery. However, the kinetics of NT-proBNP in healthy patients undergoing non-cardiac surgery are unknown.

Design & Methods: A secondary analysis of a prospective cohort study was conducted.

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Background And Aims: The cardiovascular hormones renin/angiotensin/aldosterone (RAA), brain-type natriuretic peptide (BNP)and arginine-vasopressin (AVP) are key regulators of systemic circulatory homeostasis in portal hypertension (PH). We assessed (i) the activation of renin, BNP and AVP across distinct stages of PH and (ii) whether activation of these hormones correlates with clinical outcomes.

Methods: Plasma levels of renin, proBNP and copeptin (AVP biomarker) were determined in 663 patients with advanced chronic liver disease (ACLD) undergoing hepatic venous pressure gradient (HVPG) measurement at the Vienna General Hospital between 11/2011 and 02/2019.

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Background & Aims: Experimental data indicates that placental growth factor (PLGF) is involved in the pathophysiology of portal hypertension (PH) due to advanced chronic liver disease (ACLD). We investigated serum levels of PLGF and its "scavenger", the receptor soluble fms-like tyrosine kinase-1 (sFLT1, or sVEGFR1), in ACLD patients with different severity of PH and portal-hypertensive gastropathy (PHG).

Methods: PLGF and sVEGFR1 were measured in ACLD patients with hepatic venous pressure gradient (HVPG) ≥6 mmHg (n = 241) and endoscopic evaluation of PHG (n = 216).

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Childhood obesity is an increasing health care problem associated with insulin resistance and low-level systemic inflammation, which can ultimately lead to diabetes. Evidence for efficacy of therapeutic intervention programs on the early development of obesity associated sequelae is moderate. This paper investigates the effect of a multidisciplinary short-term intervention program on insulin resistance and metaflammation in childhood obesity.

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Objectives: Neurologic outcome prediction in out-of-hospital cardiac arrest survivors is highly limited due to the lack of consistent predictors of clinically relevant brain damage. The present study aimed to identify novel biomarkers of neurologic recovery to improve early prediction of neurologic outcome.

Design: Prospective, single-center study, SETTING:: University-affiliated tertiary care center.

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Human immunodeficiency virus (HIV)-induced metabolic abnormalities and antiretroviral therapy (ART), genetic factors, most importantly the rs738409 C > G p.I148M variant in the patatin-like phospholipase domain containing 3 (PNPLA3)-gene, as well as hepatitis C virus (HCV) coinfection may all cause hepatic steatosis (HS). However, recent studies suggest a protective effect of HCV infection on HS.

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Elevated levels of troponin are associated with future major adverse cardiac events (MACE). Data on the prognostic value of high sensitive troponin T (hs-TnT) compared to high sensitive troponin I (hs-TnI) in diabetic and non-diabetic patients are sparse. We analyzed patients of a single-center registry undergoing coronary stenting between 2003 and 2006.

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Background: Although chronic alcohol consumption in adults is an established risk factor for osteoporotic fractures, there is a huge gap in our knowledge about bone effects of binge drinking in adolescents. The aim of this pilot study was therefore to assess skeletal effects of binge alcohol drinking using prepubescent pigs as a large animal model.

Methods: Piglets aged 2 months were offered alcohol orally as a mixture of hard liquor and apple juice.

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Resveratrol is a naturally occurring polyphenolic compound with various pharmacological activities. It is unknown whether the expression of metabolizing enzymes correlates with resveratrol levels in organs and tissues. Therefore, we investigated the metabolism and tissue distribution of resveratrol in mice and assessed its association with the expression of UDP-glucuronosyltransferase (Ugt) and sulfotransferase (Sult) genes.

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Scope: Oxidative imbalance plays a key role in cancer induction and cardiovascular diseases (CVD) in patients with type 2 diabetes mellitus (T2DM). The aim of this study is to find out if gallic acid (GA) prevents oxidative stress in diabetic patients. Therefore, we investigate its impact on oxidation of DNA bases and on other health-related macromolecules.

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Cellular growth inhibition exerted by thiosemicarbazones is mainly attributed to down-regulation of ribonucleotide reductase (RNR) activity, with RNR being responsible for the rate-limiting step of de novo DNA synthesis. In this study, we investigated the antineoplastic effects of three newly synthesized thiosemicarbazone derivatives, thiazolyl hydrazones, in human HL-60 promyelocytic leukemia cells. The cytotoxicity of compounds alone and in combination with arabinofuranosylcytosine (AraC) was determined by growth inhibition assays.

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Background: Irreproducibility of scientific results constitutes an undesirably onerous economic burden and is in many cases caused by low-quality materials. Therefore, researchers are increasingly devoting their attention to the bioresources they use. In turn, those bioresources are required to validate their preanalytical processes in order to ensure best possible quality.

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Secretion of 12(S)-HETE by breast cancer emboli provokes "circular chemorepellent induced defects" (CCIDs) in the adjacent lymphatic vasculature facilitating their intravasation and lymph node metastasis which determines prognosis. Therefore, elucidating the mechanism of lymph endothelial cell (LEC) wall disintegration may provide cues for anti-metastatic intervention. The role of intracellular free Ca(2+) for CCID formation was investigated in LECs using MCF-7 or MDA-MB231 breast cancer cell spheroids in a three-dimensional cell co-culture model.

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Plants and plant extracts play a crucial role in the research into novel antineoplastic agents. Four sesquiterpene lactones, artecanin (1), 3β-chloro-4α,10α-dihydroxy-1α,2α-epoxy-5α,7αH-guaia-11(13)-en-12,6α-olide (2), iso-seco-tanapartholide 3-O-methyl ether (3) and 4β,15-dihydro-3-dehydrozaluzanin C (4), were isolated from two traditionally used Asteraceae species (Onopordum acanthium and Artemisia asiatica). When tested for antiproliferative action on HL-60 leukemia cells, these compounds exhibited reasonable IC50 values in the range 3.

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Scope: Xanthohumol (XN) is a hop flavonoid found in beers and refreshment drinks. Results of in vitro and animal studies indicate that it causes beneficial health effects due to DNA protective, anti-inflammatory, antioxidant, and phytoestrogenic properties. Aim of the present study was to find out if XN causes alterations of health-related parameters in humans.

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Background: The t(2;5)(p23;q35) chromosomal translocation results in the expression of the fusion protein NPM/ALK that when expressed in T-lymphocytes gives rise to anaplastic large cell lymphomas (ALCL). In search of new therapy options the dichloromethane extract of the ethnomedicinal plant Neurolaena lobata (L.) R.

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HIV resistance to current anti-HIV drugs and drug toxicity have created a need for new anti-HIV agents. We have examined and characterized a synthetic resveratrol analog, termed 3,3',4,4',5,5'-hexahydroxy-trans-stilbene (M8), for potential anti-HIV activity. Here, we demonstrate that M8 possesses potent anti-HIV activity against several HIV variants with EC50 values in the low μM range.

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