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Lege Artis Medicinae

NOVEMBER 30, 2020

[Second game, 37th move and Fourth game 78th move]

VOKÓ Zoltán

[What has Go to do with making clinical decisions? One of the greatest intellectual challenges of bedside medicine is making decisions under uncertainty. Besides the psychological traps of traditionally intuitive and heuristic medical decision making, lack of information, scarce resources and characteristics of doctor-patient relationship contribute equally to this uncertainty. Formal, mathematical model based analysis of decisions used widely in developing clinical guidelines and in health technology assessment provides a good tool in theoretical terms to avoid pitfalls of intuitive decision making. Nevertheless it can be hardly used in individual situations and most physicians dislike it as well. This method, however, has its own limitations, especially while tailoring individual decisions, under inclusion of potential lack of input data used for calculations, or its large imprecision, and the low capability of the current mathematical models to represent the full complexity and variability of processes in complex systems. Nevertheless, clinical decision support systems can be helpful in the individual decision making of physicians if they are well integrated in the health information systems, and do not break down the physicians’ autonomy of making decisions. Classical decision support systems are knowledge based and rely on system of rules and problem specific algorithms. They are utilized widely from health administration to image processing. The current information revolution created the so-called artificial intelligence by machine learning methods, i.e. machines can learn indeed. This new generation of artificial intelligence is not based on particular system of rules but on neuronal networks teaching themselves by huge databases and general learning algorithms. This type of artificial intelligence outperforms humans already in certain fields like chess, Go, or aerial combat. Its development is full of challenges and threats, while it presents a technological breakthrough, which cannot be stopped and will transform our world. Its development and application has already started also in the healthcare. Health professionals must participate in this development to steer it into the right direction. Lee Sedol, 18-times Go world champion retired three years after his historical defeat from AlphaGo artificial intelligence, be­cause “Even if I become the No. 1, there is an entity that cannot be defeated”. It is our great luck that we do not need to compete or defeat it, we must ensure instead that it would be safe and trustworthy, and in collaboration with humans this entity would make healthcare more effective and efficient. ]

Clinical Oncology

DECEMBER 30, 2019

[Sequential therapy of metastatic renal cell carcinoma]


[The incidence of renal carcinoma is on the rise in developed countries, with the tumor being among the 10 most common malignancies. However, the survival of patients with irresecable renal carcinoma has improved signifi cantly in recent years, mainly due to signifi cant advances in oncology treatment. The use of agents acting on the VEGF and mTOR signaling pathways is widespread and has become a standard clinical practice in fi rst and later line therapy. Recent clinical trials have provided many new drugs with new targets (cMET and AXL, FGFR, PD-1/PD-L1, CTLA-4) and combinations thereof, and have completely redrawn the treatment landscape of metastatic renal carcinoma and signifi cantly improved clinical results. This report reviews data on targeted drug therapy of renal cell carcinoma and discusses the therapeutic position of various drugs and combinations to our knowledge.]

Clinical Oncology

DECEMBER 30, 2019

[Cell death]

KOPPER László, TÍMÁR József

[Cell proliferation and cell death (mainly apoptosis) have programs forming a network to maintain the functional integrity of the organism. Apoptosis has an external and internal units with ligands, signalling pathways and targets. Besides, some other participants (e.g. p53) are involved in the regulation of cell death. Although, apoptosis is a multitargeted process, there is no useful therapy, if it is needed, to correct accumulation of unwanted cells.]

Clinical Oncology

AUGUST 30, 2019

[Role of calcium metabolism in malignant diseases]


[Calcium plays a key role in a wide range of biologic functions. It is involved in skeletal mineralization, muscle functions, nerve transmission, and hormonal secretion and modulate various cellular functions too. Lines of research, on possible association of calcium metabolism regulation with tumorigenesis have been extensively studied in the recent decades. Implying disruptions and/or alterations of known regulatory and molecular pathways can lead to severe, sometimes life-threatening complications. The shift in physiological regulation and pathological factors also affect bone metastases and hypercalcaemia in cancer patients. For this reason, it is important to know about the changes in calcium metabolism and its treatment options in cancerous diseases.]

Clinical Neuroscience

SEPTEMBER 30, 2020

TLR4 (Toll-like receptor-4) expression and frontal-cingulate volumes in schizophrenia

LI Hua, KÉRI Szabolcs

Evidence suggests that pathogen-associated pattern recognition receptors (Toll-like receptors, TLRs) are implicated in the pathophysiology of schizophrenia. TLRs are important in both peripheral immune responses and neuronal plasticity. However, the relationship between peripheral TLR expression and regional brain volumes is unknown in schizophrenia. We therefore assessed 30 drug-naïve, first-episode patients with schizophrenia. TLR4+/TLR1+ monocytes were measured using flow-cytometry. High resolution magnetic resonance images (T1 MRI) were obtained and analyzed with FreeSurfer. Results revealed significant negative correlations between the percentage of TLR4+ monocytes, mean fluorescent intensities, and brain volumes in frontal and anterior cingulate regions. The measures of TLR1+ monocytes did not show significant relationships with regional brain volumes. These results raise the possibility that abnormal TLR-activation is associated with decreased brain volumes in schizophrenia.

Clinical Neuroscience

SEPTEMBER 30, 2020

Neuroscience highlights: Main cell types underlying memory and spatial navigation

KRABOTH Zoltán, KÁLMÁN Bernadette

Interest in the hippocampal formation and its role in navigation and memory arose in the second part of the 20th century, at least in part due to the curious case of Henry G. Molaison, who underwent brain surgery for intractable epilepsy. The temporal association observed between the removal of his entorhinal cortex along with a significant part of hippocampus and the developing severe memory deficit inspired scientists to focus on these regions. The subsequent discovery of the so-called place cells in the hippocampus launched the description of many other functional cell types and neuronal networks throughout the Papez-circuit that has a key role in memory processes and spatial information coding (speed, head direction, border, grid, object-vector etc). Each of these cell types has its own unique characteristics, and together they form the so-called “Brain GPS”. The aim of this short survey is to highlight for practicing neurologists the types of cells and neuronal networks that represent the anatomical substrates and physiological correlates of pathological entities affecting the limbic system, especially in the temporal lobe. For that purpose, we survey early discoveries along with the most relevant neuroscience observations from the recent literature. By this brief survey, we highlight main cell types in the hippocampal formation, and describe their roles in spatial navigation and memory processes. In recent decades, an array of new and functionally unique neuron types has been recognized in the hippocampal formation, but likely more remain to be discovered. For a better understanding of the heterogeneous presentations of neurological disorders affecting this anatomical region, insights into the constantly evolving neuroscience behind may be helpful. The public health consequences of diseases that affect memory and spatial navigation are high, and grow as the population ages, prompting scientist to focus on further exploring this brain region.

Lege Artis Medicinae

SEPTEMBER 30, 2020

[The pain-trigger role of cytokines in the nervous system – the direct analgesic effect of anti-cytokine therapy ]


[Nociceptive, neuropathic and central me­chanisms are involved in the perception, transmission and processing of chronic pain and shaping of cerebral pain image. Alar­mins – molecules alarming defence and signing the presence of pathogens and tissue damage - trigger a series of pathogenic events resulting in inflammatory pain stimuli. Proinflammatory cytokines play a determining role in the pain perception at the level of the nervous system. Continuous inflammatory stimuli while sensitizing the periferic and central neurons activate the pain-related cerebral areas and develop the complex pain image, the pain matrix. Ce­reb­ral functional connections are operating in networks and can be visualized by functional MRI. Cytokines activate the neurons directly or indirectly by other neuromediators. Cytokine receptors are expressed on no­ciceptors and even on higher-level neurons and on various non-neural cells, such as microglia and astrocytes. The most ubiquitous cytokines are the Tumour Necrosis Factor and Interleukin 6 in the nervous sys­tem. The signaling pathways are the Nuclear Factor κB and the Janus-kinase enzyme system. The proinflammatory cytokines and the Janus-kinase are therefore primary therapeutic targets. Anti-cytokine biologicals and small molecular kinase inhibitors decrease the pain and improve functional activity in rheumatoid arthritis. Decrease of pain was more pronounced than expected only from the decrease of the clinical biomarkers of inflammation. The early and ra­pid painkiller effect of targeted biological and chemical-biological response modifiers is attributed to their direct analgesic effect on the brain.]

Clinical Neuroscience

JANUARY 30, 2016

[The propagation and semiology of focal epileptic seizures. case presentations to the insula. theoretical considerations]

BALOGH Attila, BALOGH Attila ifj.

[Study objectives – The developing of diagnostical examinations in epileptology provides new challenges in seizure semiology. On the analysis of seizures it is important to examine the mechanisms of their propagation. The brain connectivity (based on the neuroimaging), the shadowing of the movement of excessive neuronal activity (based on computerized EEG and MEG methods), the cognition of the physiological and pathological brain networks are the foot- stone of the epileptic seizure propagation. The investigators prove, by means of case demonstrations of the role of the network nodes and the role of the epileptic hubs in the seizure symptomatology. Methods – The preoperative, intra and postoperative data are analised of three insular and one parietal epileptic patients in point of view of their seizure symptomes. Complex neuroimaging, noninvasive and invasive electrophysiology, intensive long-term video-EEG monitoring, computerized EEG analysis, fuctional mapping, intraoperative corticography were used. The etiology were confirmed with hystology. Results – It is observed that on seizure semiology our patients plays the insula a double role. In some cases, it is the focus of insular seizures with their symptoms difficult to identify. However, in the majority of cases and as a consequence of its rich neural connections, the insula has a peculiar property in the evolution of the symptomatogenic features of seizures. This observations are developing new relationships between the mechanism of seizure propagation and its semiological consequences. Conclusions – On epileptological point of view there are brain structures which has peculiar role in the „designe” of propagation of the epileptic excitement. The numerous new methods in neuroimaging and neurophysiology allowed the connectomical examination of the epileptic networks. The role of the epileptic diathesis is approachable with the metholdology of the brain connectivity. Theoretically the node of the epileptic network consist of the potential pathes where the localised excessive excitement can propagete. The route where the actual seizure can go adhead is determined by the actual edpileptic propensity of the above mentioned potential pathes.]

Lege Artis Medicinae

APRIL 18, 2020

[About general practitioners in Hungary - without political roadblocks]


[A brief introduction about the primary care’s evolution is rather improving the clear sight since it supports our right judgement and helps to draw right consequences. Thus, we are able to realise more precisely our strategic aims, actual domestic problems, and the forced pathways indicated by the prevailing trends and the action radius of our reform endeavours. The present study shows hidden risks encoded in human resources, specialists’ services and shed light into the grey zone of remuneration. Indeed, the trends are alarming, the spaces are narrow for actions nevertheless we can escape our century old legacy by innovative solutions. While re-thinking totally the whole system nevertheless maintaining all immanent principles we can just in the short run revitalise our ailing primary health care. ]

Lege Artis Medicinae

OCTOBER 20, 2019

[Population-level QALY gain estimates with the use of cariprazine for patients with negative symptoms of schizophrenia in Hungary]

BENDES Rita, NÉMETH Bertalan, PITTER János György, KÓCZIÁN Kristóf, GÖTZE Árpád, KALÓ Zoltán

[INTRODUCTION - The loss in quality of life caused by mental illnesses has been growing in developed countries. This study aims to quantify the possible gains in quality of life by advantages of cariprazine therapy while treating patients with negative symptoms of schizophrenia in Hungary. Comparator therapy was defined as the currently available second-generation oral antipsychotic drugs. METHODS - In order to estimate the reachable gain in quality of life with cariprazine, an 8-state deterministic Markov cohort model was developed. Data was gathered from relevant scientific literature and public databases. The main assumptions regarding patient pathways have been validated by clinical experts, based on their real-life experience. The number of patients with negative symptoms of schizophrenia was estimated by the same methods as well. Sensitivity analyses were conducted on the input parameters. RESULTS - When compared with currently available second-generation oral antipsychotics, cariprazine generated an estimated increase of 0.05 quality-adjusted life years per patient in 2 years run. The deterministic sensitivity analysis confirmed the robustness of the results. Based on data of the National Health Insurance Fund and the scientific literature, a total gain of 450 quality-adjusted life years is expected at national level over a time horizon of 2 years. Even higher gains of QALY can be expected for longer time horizons. CONCLUSION - Based on conservative estimates significant health gain can be ge­ne­rated, if all patients with negative symp­toms of schizophrenia would receive the adequate cariprazine therapy in Hungary in­stead of the currently used se­cond-ge­ne­ration oral antipsychotic drugs. ]