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Lege Artis Medicinae

APRIL 18, 2020

[Digitally-assisted treatment planning in precision oncology]

PETÁK István, VÁLYI-NAGY István

[The progress of molecular information based on personalized precision medicine has reached a new milestone. Actually, about 6 million mutations of 600 genes may be related to the development of cancer, and on average, 3-4 of these “driver” mutations are present in each patient. Due to the progress in molecular diagnostics, we can now routinely identify the molecular profile of tumors in clinical settings. By clinical translation, there are actually available more than 125 targeted pharmaceuticals and hundreds of such therapies are under clinical trial. As a result, we have many first-line and licenced treatment options to be elected by molecular information as the optimal one for every patient. There is an increasing need for complex informatics solutions by medical software. Geneticists, molecular biologists, molecular pathologists, molecular pharmacologists are already using bioinformatics and interpretation software on their daily work. Today, online digital tools of artificial intelligence are also available for physicians for assisted treatment planning. Telemedicine, videoconferencing provide solutions for interdisciplinary virtual molecular tumor boards, which democratizes the access to precision oncology for all doctors and patients. ]

Clinical Oncology

APRIL 10, 2019

[Metals and cancer]

VETLÉNYI Enikő, RÁCZ Gergely

[We often tend to forget about our environment when looking for the origin of a disease. Inhaled air, drinking water and food, substances in contact with the skin all have an effect on the human body. Metals are indispensable parts of our everyday lives, their mining, processing and use cause a continuous exposure to them. Metal exert their effects on the body in various ways. Many of them are essential for maintaining homeostasis, but excessive or harmful metal intake can lead to health damage, including tumour formation through multiple attack points. Metals substitute each other during different transport processes and in the structure of proteins, they cause oxidative stress and bind to DNA, thereby damaging it. Applying them appropriately, the proapoptotic effect of the metal compounds is brought to the fore, thus becoming a therapeutic tool for tumours. Nowadays, platinum(II) compounds are widely used as chemotherapeutic agents and there are many ongoing studies to fi nd metal compounds with an ideal therapeutic and side-effect profi le. The aims of this article were to draw the attention to the dangers of metals in relation to cancer and to highlight their diverse application possibilities in current and future cancer therapy and diagnostics.]

Hypertension and nephrology

SEPTEMBER 30, 2020

[Post-career development of cardiometabolic changes and hypertension in competitive athletes]

LELBACH Ádám, KÁNTOR Márk, KOLLER Ákos

[Regular physical activity is essential in delaying the aging processes (e.g. arterial remodelling – stiffening, metabolism, bodyweight), the beneficial effects of competitive sports – especially strength sports – according to the recent data of the literature are questionable. The beneficial effects of physical activity on the cardiovascular (CV) system are well known, however less is known regarding the delayed impacts of high intensity competitive sports on the CV system, especially after the sport career is over. This review summarizes the effects of active competitive sport and the post-career period on the cardiometabolic system with special attention to the systemic blood pressure and the development of metabolic syndrome. After sport career, the welldeveloped high performance cardiovascular- and metabolic system suddenly is much less used, but still supported by sport-level diet. It is well known that hypertension is a significant pathogenic factor in the development of cardiovascular diseases, characterized – among others – by reduced elasticity of large- and medium- sized vessels thereby importantly contributing to the development of systolic hypertension. Inflammation and thrombus formation both play an important role in the development of vascular injury and atherosclerosis. The increased tone of microvessels can impair the blood supply of certain organs, including the coronary circulation. It has been ample shown, that regular non-competitive, aerobic exercise activities are important factors in preventing hypertension. Such pathological changes become more evident after the development of post-career obesity, as well as the development of hypertension due to the activation of the renin-angiotensin system through sodium retention and other metabolic changes (increased glucose tolerance, insulin resistance, type II diabetes mellitus). It has been ample shown, that regular non-competitive, dynamic aerobic exercise activities are important factors in preventing hypertension. The frequency, intensity, type, and time (FITT) principle of exercise prescription is the first and common therapeutic approach, which represents the translation of cardiovascular basic science research results into hypertension treatment, thus can provide a personalized physical activity program/therapy according to medical needs not just for the post-career sportspersons, but the wide range of patients.]

Clinical Neuroscience

SEPTEMBER 30, 2020

Late simultaneous carcinomatous meningitis, temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting with mono-symptomatic vertigo – a clinico-pathological case reporT

JARABIN András János, KLIVÉNYI Péter, TISZLAVICZ László, MOLNÁR Anna Fiona, GION Katalin, FÖLDESI Imre, KISS Geza Jozsef, ROVÓ László, BELLA Zsolt

Although vertigo is one of the most common complaints, intracranial malignant tumors rarely cause sudden asymmetry between the tone of the vestibular peripheries masquerading as a peripheral-like disorder. Here we report a case of simultaneous temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting as acute unilateral vestibular syndrome, due to the reawakening of a primary gastric signet ring cell carcinoma. Purpose – Our objective was to identify those pathophysiological steps that may explain the complex process of tumor reawakening, dissemination. The possible causes of vestibular asymmetry were also traced. A 56-year-old male patient’s interdisciplinary medical data had been retrospectively analyzed. Original clinical and pathological results have been collected and thoroughly reevaluated, then new histological staining and immunohistochemistry methods have been added to the diagnostic pool. During the autopsy the cerebrum and cerebellum was edematous. The apex of the left petrous bone was infiltrated and destructed by a tumor mass of 2x2 cm in size. Histological reexamination of the original gastric resection specimen slides revealed focal submucosal tumorous infiltration with a vascular invasion. By immunohistochemistry mainly single infiltrating tumor cells were observed with Cytokeratin 7 and Vimentin positivity and partial loss of E-cadherin staining. The subsequent histological examination of necropsy tissue specimens confirmed the disseminated, multi-organ microscopic tumorous invasion. Discussion – It has been recently reported that the expression of Vimentin and the loss of E-cadherin is significantly associated with advanced stage, lymph node metastasis, vascular and neural invasion and undifferentiated type with p<0.05 significance. As our patient was middle aged and had no immune-deficiency, the promoting factor of the reawakening of the primary GC malignant disease after a 9-year-long period of dormancy remained undiscovered. The organ-specific tropism explained by the “seed and soil” theory was unexpected, due to rare occurrence of gastric cancer to metastasize in the meninges given that only a minority of these cells would be capable of crossing the blood brain barrier. Patients with past malignancies and new onset of neurological symptoms should alert the physician to central nervous system involvement, and the appropriate, targeted diagnostic and therapeutic work-up should be established immediately. Targeted staining with specific antibodies is recommended. Recent studies on cell lines indicate that metformin strongly inhibits epithelial-mesenchymal transition of gastric cancer cells. Therefore, further studies need to be performed on cases positive for epithelial-mesenchymal transition.

Clinical Neuroscience

SEPTEMBER 30, 2020

[The public’s attitudes towards electroconvulsive therapy in Hungary ]

ASZTALOS Márton, KÖNYE Péter, GAZDAG Gábor

[This research focused on the knowledge and attitude toward to electroconvulsive therapy (ECT) in the general population of Hungary. There are only a few studies in the international literature focusing on the public’s attitude towards ECT, and no such study has been published from Hungary. Participants were reached through social media and asked to fill out a semi-structured questionnaire on internet that comprised seventeen questions. Participation in the survey was entirely voluntary and anonymous. Participants of the survey were not working in health care; their answers to the questionnaire were compared to those of health-care workers. The result showed a significant difference between healthcare workers’ and lay people’s knowledge and attitude towards ECT. Two third of lay participants have never heard about ECT. Those familiar with ECT were relatively well-informed about its certain aspects yet rejection of ECT was significantly higher in the group of lay participants than in health-care workers. Lay people’s incomplete knowledge and negative attitude towards ECT was confirmed by this survey. The dissemination of reliable information – which should be the shared responsibility of mental health professionals and the media – would be vitally important to disperse the prejudices and doubts about ECT.]

Clinical Neuroscience

SEPTEMBER 30, 2020

[Pompe disease treated with enzyme replacement therapy in pregnancy]

GROSZ Zoltán, VÁRDI Visy Katalin, MOLNÁR Mária Judit

[Pompe disease is a rare lysosomal storage disease inherited in a recessive manner resulting muscular dystrophy. Due to the lack of the enzyme alpha glucosidase, glycogen accumulates in the cells. In the infantile form of Pompe disease hypotonia and severe cardio-respiratory failure are common leading to death within 2 years if left untreated, while the late-onset form is characterized with limb-girdle and axial muscle weakness accompanied with respiratory dysfunction. Pompe disease has been treated with regular intake of the missing enzyme since 2006, which significantly improved the survival and severity of symptoms in patients of both subtypes. The enzyme replacement therapy (ERT) is safe and well tolerated. However, limited data are available on its use in pregnancy. Our goal is to share our experience and review the literature on the safety of enzyme replacement therapy for Pompe disease during pregnancy and post partum.]

Clinical Neuroscience

SEPTEMBER 30, 2020

A rare entity of acquired idiopathic generalised anhidrosis which has been successfully treated with pulse steroid therapy: Does the histopathology predict the treatment response?

ÖKTEM Özdemir Ece, ÇANKAYA Şeyda, UYKUR Burak Abdullah, ERDEN Simsek Nazan, YULUG Burak

Acquired idiopathic generalised anhidrosis is an uncommon sweating disorder characterized by loss of sweating in the absence of any neurologic, metabolic or sweat gland abnormalities. Although some possible immunological and structural mechanisms have been proposed for this rare entity, the definitive pathophysiology is still un­clear. Despite some successfully treated cases with systemic corticosteroid application, the dose and route of steroid application are controversial. Here, we present a 41-year-old man with lack of genera­lised sweating who has been successfully treated with high dose pulse intravenous prednisolone. We have discussed his clinical and histopathological findings as well as the treatment options in view of the current literature.

Lege Artis Medicinae

SEPTEMBER 30, 2020

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

HODINKA László, VERECKEI Edit

[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.]

Lege Artis Medicinae

SEPTEMBER 30, 2020

[Frequency and risk factors of “de novo” tumors after kidney transplantation ]

BORDA Bernadett, HÓDI Zoltán, SZEDERKÉNYI Edit, OTTLAKÁN Aurél, SEREGÉLY Edit, LÁZÁR György, KERESZTES Csilla, VIRÁG Katalin

[After kidney transplantation, the administration of immunosuppressive therapy not only renders the patient susceptible to infections, but it may also damage the function of tumor cell recognition and elimination. Our study was performed at the Department of Surgery, University of Szeged. After establishing the inclusion criteria, 570 patients were involved in the study. We examined the age, sex, immunosuppressive therapy of the patients, and searched for the rela­tionship between the different immunosuppressive agents and the type of the tumor. In 81 cases, de novo cancer was diagnosed. Among patients treated with cyclosporin and tacrolimus there was no significant difference in the mean age (p = 0.734) and body mass index (p = 0.543). There was no significant difference in graft function between the two groups of patients (Tac vs Cyc; 44 vs 20). Related to the time passed since the trans­plantation to diagnosing the tumors the earliest were prostate and cervix cancers however without significant difference. Skin cancers are the most frequent followed by post-transplant lym­pho­prolife­ra­tive diseases. The increasing risk of developing tumors is mainly due to immunosuppressive therapy. ]

Lege Artis Medicinae

JULY 01, 2020

[Sarcopenia – muscle loss – pathomechanism, clinical presentation and metabolic comorbidities]

VERECKEI Edit, HODINKA László

[Sarcopenia, or the age-related involution of muscle strength and muscle mass, is a serious public health concern, due to the growing number of elderly population caused by nowadays demographic changes i.e. prolonged life expectancy. By ageing, the muscle tissue is shrinking gradually, leading to the loss of muscle strength and masses. This condition is called sarcopenia. Sar­co­penia is the simultaneous decrease of muscle mass, muscle strength and functional independence. In parallel the physical performance deteriorates (weakness, slowness and poor physical balancing). Fatigue, el­derly behaviour and weight loss are the consequences of these accumulating deficits, which associate with cognitive decline and result in increasing social isolation. The primary form of sarcopenia is the decrease of the energy production of muscle cells and then the death of muscle cells. Se­con­dary, endocrine dysfunctions, diseases of the nervous system, decreased physical activity, malnutrition or malabsorption, chronic infection accelerate the process and aggravate the patient’s condition. Complex genetic, biochemical and endocrine mechanisms take part in the development of sarcopenia. This involution is due to the impaired balance of restoring and depleting processes of muscles. A questionnaire and algorithm have been developed to recognize, screen and diagnose the risks of sarcopenic condition; these separate the sarcopenic and non-sarcopenic patients with specific cut-off values. Sar­co­penia can be diagnosed based on walking speed, decreased handgrip strength and measured or calculated muscle mass in persons over 65. Sarcopenia can be considered as a phenomenon of “physiological” aging, however, it becomes a disease when diagnostic cut-offs are exceeded and the patient experiences functional disability and declining quality of life. Prevention and treatment of sarcopenia and reducing the risk of falling are based on regular active resistance and coordination exercises. Options for pharmaceutical treatments are limited since despite of identified molecular targets there are no convincingly effective innovative therapy on the horizon. Nevertheless, there are some weak evidence for efficacy of the application of amino acids stimulating muscle cell differentiation, such as leucine or the analogue of beta-hydoxy-methylbutyrate beside exercise therapy.]