Search results

Clinical Neuroscience

JANUARY 30, 2021

Matrix metalloproteinases and their tissue inhibitors in relapsing remitting multiple sclerosis: Possible markers and treatment agents


Matrix metalloproteinases (MMPs), which are synthesized by many cell groups and responsible for the destruction of matrix proteins, and endogen tissue inhibitors of MMPs (TIMPs) have a role in the pathogenesis of Multiple Sclerosis (MS) by affecting the blood-brain barrier. We aimed to investigate the role of MMPs and TIMPs in the immunopathogenesis and in the course of multiple sclerosis (MS). We enrolled 25 relapsing remitting MS patients, who had a definite MS diagnosis according to McDonald criteria and 25 healthy subjects similar for age and gender as control group. MMP-9- and TIMP-1 levels were measured twice in patient group (one time during an attack and one in remission) and once in healthy subjects. MMP-9- and TIMP-levels of patients during attack and remission period and MMP-9/TIMP-1 ratio were found significantly higher than in the control subjects. In patient group MMP-9 and TIMP-1 levels and MMP-9/TIMP-1 ratio during attacks were not significantly different than during remission period. However, when subdivided according to their number of attacks, patients with 2 attacks had significantly higher levels during attack period comparing to remission period (p<0.05); in case of patients with more than 2 attacks did not have a statistically significant difference in attack and remission periods. Matrix metalloproteinases are important actors in MS immunopathogenesis, particularly in the early period and inhibitor agents for these enzymes can be used as a treatment option.

Clinical Oncology

APRIL 30, 2020

[Molecular residual tumor monitoring in solid cancers]

SZÁSZ A. Marcell, TOBIÁS Bálint, KÓSA János, LAKATOS Péter

[Blood-based diagnostics has long been used in the oncological practice of solid tumors, but its full potential is just unfolding recently. Quantitative measurement of tumor markers, circulating tumor cells, and some of their products or components have now become available and are part of a multimodal system that provides additive parameters in clinical decision making. The most challenging oncological questions can be answered by the detection, characterization and measurement of circulating free DNA (cfDNA), which, due to its growing importance, bears the potential of incorporation into routine practice. In this overview, we review the „blood impressions” of solid tumors and present the most promising results in different patient groups, especially in lung, breast, colon, and bladder tumors, which are also valid for other solid tumors.]

Clinical Oncology

FEBRUARY 28, 2020

[Treatment sequencing in metastatic colorectal cancer]


[Metastatic colorectal cancer (mCRC) remains incurable in most cases, but survival has improved with advances in cytotoxic chemotherapy and targeted agents. However, the optimal use and sequencing of these agents across multiple lines of treatment is unclear. Here, we review current treatment approaches and optimal treatment sequencing across the fi rst-, second- and third-line settings in mCRC, including biological aspects affecting sequencing and rechallenge. Effective fi rst-line therapy is a key determinant of treatment outcomes and should be selected after considering both clinical factors and biological markers, notably RAS and BRAF. The second-line regimen choice depends on the systemic therapies given in fi rst-line. Anti-angiogenic agents (e.g. bevacizumab, ramucirumab and afl ibercept) are indicated for most patients, whereas epidermal growth factor receptor (EGFR) inhibitors do not improve survival in the second-line setting. Molecular profi ling is important in thirdline treatment, with options in RAS wild-type patients including EGFR inhibitors (cetuximab or panitumumab), regorafenib and trifl uridine/tipiracil. Immunotherapy with pembrolizumab or nivolumab ± ipilimumab may be considered for patients with high microsatellite instability disease. Targeting HER2/neu amplifi cation shows promise for the subset of CRC tumours displaying this abnormality. Sequencing decisions are complicated by the potential for any treatment break or de-escalation to evoke a distinct clinical progression type. Ongoing trials are investigating the optimal sequencing and timing of therapies for mCRC. Molecular profi ling has established new targets, and increasing knowledge of tumour evolution under drug pressure will possibly impact on sequencing.]

Hypertension and nephrology

SEPTEMBER 30, 2020

[Association between cyclothymic affective temperament and hypertension]


[Affective temperaments (cyclothymic, hypertymic, depressive, anxious, irritable) are stable parts of personality and after adolescent only their minor changes are detectable. Their connections with psychopathology is well-described; depressive temperament plays role in major depression, cyclothymic temperament in bipolar II disorder, while hyperthymic temperament in bipolar I disorder. Moreover, scientific data of the last decade suggest, that affective temperaments are also associated with somatic diseases. Cyclothymic temperament is supposed to have the closest connection with hypertension. The prevalence of hypertension is higher parallel with the presence of dominant cyclothymic affective temperament and in this condition the frequency of cardiovascular complications in hypertensive patients was also described to be higher. In chronic hypertensive patients cyclothymic temperament score is positively associated with systolic blood pressure and in women with the earlier development of hypertension. The background of these associations is probably based on the more prevalent presence of common risk factors (smoking, obesity, alcoholism) with more pronounced cyclothymic temperament. The scientific importance of the research of the associations of personality traits including affective temperaments with somatic disorders can help in the identification of higher risk patient subgroups.]

Clinical Neuroscience

SEPTEMBER 30, 2020

[Prognostic significance of invasion in glioblastoma]


[Glioblastoma is the most common malignant CNS tumor, its surgical removal is hindered by the tumors invasive nature, while current anti-tumor therapies show limited effectiveness – mean overall survival is 16-24 months. Some patients show minimal response towards standard oncotherapy, however there are no routinely available prognostic and predictive markers in clinical practice to identify the background of mentioned differences in prognosis. This research aims to identify the prognostic significance of invasion-related extracellular (ECM) components. Patient groups with different prognoses were created (OS: group A <16 months, group B > 16 months), and internationally recognized prognostic markers (IDH1 mutation and MGMT promoter hyper-methylation) were tested in the flash-frozen tumor samples. Furthermore, the mRNA levels of 46 invasion-related ECM molecules were measured. Clinical data of the patients who have been operated on at the University of Debrecen Clinical Center Department of Neurosurgery and treated at the Department of Clinical Oncology showed no significant differences except for survival data (OS and PFS), and reoperation rate. All samples were IDH wild type. MGMT promoter hypermethylation rate showed significant differences (28.6% vs 68.8%). The expressional pattern of the invasion-related ECM molecules, i.e. the invasion spectrum also showed major differences, integrin β2, cadherin-12, FLT4/VEGFR-3 and versican molecules having signficantly different mRNA levels. The accuracy of the inivasion spectrum was tested by statistical classifier, 83.3% of the samples was sorted correctly, PPV was 0.93. The difference found in the reoperation rate when comparing different prognostic groups aligns with literature data. MGMG promoter region methylation data in Hungarian samples has not been published yet, and further confirming current knowledge urges the implementation of MGMT promoter analysis in clinical practice. Studying the invasion spectrum provides extra information on tumors, as a prognostic marker it helps recognizing more aggressive tumors, and calls attention to the necessity of using anti-invasive agents in GBM therapies in the future.]

Lege Artis Medicinae

APRIL 18, 2020

[The relationship of traumatic experiences and eating disorders – therapeutical options]


[In the etiology of eating disorders (espe­cially bulimia nervosa and binge eating) traumatic experiences (sexual, physical, emo­tional abuse, neglect) play an important role. Traumatization can have a serious impact, which is influenced by the parameters of the traumatization, risk and protective factors, and the resiliency of the traumatized patient. The consequences may lead to the development of specific psychiatric and somatic disorders, and may cause lifetime revictimization. The exploration of data related to the traumatization is essential in eating disorders as well. If traumatic expericences can be detected in the back­ground of eating disorders, the targeted therapy of eating disorders while applying its specific elements should also follow the guide­lines of the general trauma-therapy. Providing safety in therapeutical relation­ship is fundamental. The therapeutic options are extensive. Along with psychodynamically oriented therapies, the newer methods based on cognitive-behavioral therapy (e.g., dialectic behavior therapy, integrative cognitive analytic therapy) are also proposed. Hyp­no­therapy can also be useful. ]

Lege Artis Medicinae

JANUARY 20, 2020

[Personality development in East and West, and some clinical implications ]


[Exploring human personality focused mainly on trait and state markers of behaviour so far. Nevertheless, the concept of the universal, culture-independent model of personality carries more disturbing difficulties: hardly understandable inter-cultural conflicts, culture-related mental disorders and scientific experiences with unexpected outcomes. It can be hypothesized, that beside personality concept represented by the Euro-Atlantic civilisation and mainstream psychology there is an alternative concept of personality. Opposed to the independent, autonomous ego concept of individualistic cultures, collectivistic (primarily far-eastern) cultures are providing an interdependent model. According to this model, the core element of personality are determined rather by social embedding instead of the person’s own characteristics, which are secondary to the personal traits and characteristics. This study attempts to briefly outline the concept of interdependent personality, with some illustrative clinical examples. ]

Clinical Oncology

FEBRUARY 20, 2019

[Molecular subtypes and the evolution of treatment decisions in metastatic colorectal cancer]

RODRIGO Dienstmann, RAMON Salazar, JOSEP Tabernero

[Colorectal cancer (CRC) has clinically-relevant molecular heterogeneity at multiple levels: genomics, epigenomics, transcriptomics and microenvironment features. Genomic events acquired during carcinogenesis remain drivers of cancer progression in the metastatic setting. For example, KRAS and NRAS mutations defi ne a population refractory to EGFR monoclonal antibodies, BRAFV600E mutations associate with poor outcome under standard therapies and response to targeted inhibitors in combinations, while HER2 amplifi cations confer unique sensitivity to double HER2 blockade. Multiple rare gene alterations driving resistance to EGFR monoclonal antibodies have been described with signifi cant overlap in primary and acquired mechanisms, in line with a clonal selection process. In this context, sequential analysis of circulating tumor DNA has the potential to guide drug development in a treatment refractory setting. Rare kinase fusion events and complex alterations in genes involved in DNA damage repair have been described, with emerging evidence for targetability. On the other hand, transcriptomic subtypes and pathway activation signatures have also shown prognostic and potential predictive value in metastatic CRC. These markers refl ect stromal and immune microenvironment interactions with cancer cells. For example, the microsatellite instable (MSI) or POLE ultramutant CRC population is particularly sensitive to immune checkpoint inhibitors, while tumors with a mesenchymal phenotype are characterized by activation of immunosuppressive molecules that mandate stratifi ed development of novel immunotherapy combinations. In this manuscript we review the expanding landscape of targetable oncogenic alterations and signatures in metastatic CRC and discuss the clinical implementation of novel molecular diagnostic tests.]

Clinical Oncology

FEBRUARY 20, 2019

[Liquid biopsy in clinical oncology – fine-tuning precision medicine]

PRISKIN Katalin, PINTÉR Lajos, JAKSA Gábor, PÓLYA Sára, KAHÁN Zsuzsa, SÜKÖSD Farkas, HARACSKA Lajos

[The classical method of genetically characterising a tumour requires tissue biopsy with which a small sample is removed from the affected organ. This sample represents the tumour in the further analyses. However, the localised nature of sample collection limits representative characterisation. The so-called circulating tumour DNA, isolated from blood plasma after a simple sample collection, potentially enables the oncological analysis of all tumour tissues carrying genetic alterations that can be identifi ed as markers. In order to maximally exploit the potentials of circulating tumour DNA, we must adjust the analytical tools to its specifi c features. The preanalytical handling and storage of the sample signifi cantly infl uences its further usability. In order to be able to detect a potential mutation in a mostly wild-type background, the development of new, specifi c methods is needed, most of which are based on next-generation sequencing techniques. In the past decades, the pronounced decrease in the costs of such techniques led to an accumulation of an immense amount of genetic information on tumorigenesis. Due to the development of sequencing technologies, the turnaround times of tests also decreased enabling their employment in routine care besides research. Starting from our research, this can be realised via three approaches: technological development, the implementation of our already existing diagnostic methods in liquid biopsy, and the construction of well-planned disease-specifi c gene panels. Based on international trends and our experience in serum diagnostics, we are certain that liquid biopsy will become a central pillar of oncological screening and precision oncology in the near future.]

Clinical Neuroscience

NOVEMBER 30, 2019

A clinical study of an online educational programme for chronic pain patients

GALAMBOS Wellingerné Krisztina, SZOK Délia, CSABAI Márta

Background - The research of alexithymia - the inability to express or understand emotions - has recently become of great importance in clinical practice, mainly in the field of doctor-patient and psychologist patient communication. Many studies have proven the correlation between alexithymia and the development of functional somatic symptoms, i.e. somatization. Purpose - The aim of this clinical study was to examine the emotion-recognition and emotion communication patterns of patients suffering from chronic pain (e.g., headache, low back pain, arthralgia, neuropathy). Moreover, the participants received access to the Hungarian adaptation of a new international online educational site ( dealing with pain management. Methods - Data were collected from the Headache and Chronic Pain Outpatient Clinic, Department of Neurology, Faculty of Medicine, University of Szeged, Hungary (tertiary care - Group 1) and from a general practice in district 2, Budapest, Hungary (primary care - Group 2) from March, 2017 to April, 2018. Patients received a test package containing a pain-specific questionnaire, then the Difficulties in Emotion Regulation Scale (DERS), the Toronto Alexithymia Scale (TAS-20), and the shortened Hungarian version of the WHO-Well-being (WBI-5) had to be completed. After filling out the questionnaires, all patients got access to the Hungarian adaptation of the website. Results - Altogether 92 patients participated in the study (Group 1 n=50; Group 2 n=42). Based on the TAS-20 re­sults, 35 patients reached a pathological score (≥60 points), which indicates the diagnosis of alexithymia. The mean TAS-score was lower in Group 2 (primary care) than in Group 1 (tertiary care) (p=0.003). The DERS disclosed pathological results in 19 cases (p=0.009). As regards the chapters, we received feedback only from 25 out of 92 patients (27%) (Group 1 n=20; Group 2 n=5). Conclusions - Although the examined patients have been suffering from different chronic pain syndromes for years and 50% of them confirmed that symptoms placed at least moderate or heavy burden on their everyday life, the available educational programme was studied only by a smaller proportion of patients than expected. Additionally, those who surveyed the Hungarian adaptation of the website were mainly patients from primary care (Group 2), in spite of the fact that patients from specialized medical care (Group 1) had worse subjective conditions. Our future objective is to extend our database with follow-up results and to improve patients’ response willingness.