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Clinical Oncology

DECEMBER 30, 2019

[Chemicals and tumors]

MARCSEK Zoltán

[Tumorigenesis is driven usually by non-lethal genetic alterations such as malfunctioning regulatory systems; mainly by inactivating suppressor genes or activating proto-oncogenes or malfunctioning of apoptatic system or decresed activity of the DNA repair system. Several chemicals induces mutations in the regulatory genes forces the cell for continous divisions increasing the chance of accumulation of further mutations. Chemicals, inducing mutations (mutagens) increase the rate of tumor occurrence, are carcinogens.]

Clinical Oncology

AUGUST 30, 2019

[Electrochemotherapy]

KIS Erika Gabriella

[Tumors with standard electrochemotherapy (ECT) has raised over the past decade from skin cancers to locally advanced or metastatic tumors. The procedure became a reliable alternative of other local tumor ablation methods, because of its patient tolerability, effi cacy across histotypes, and repeatability. ECT is based on the physical phenomenon of reversible electroporation; short electric pulses are applied to tumor nodules to achieve transient cell membrane permeabilization to otherwire poorly permeant chemotherapy drugs, which consequently increases cytotoxicity. At present recognized indications include superfi cial metastases of malignant melanoma, breast cancer, head and neck skin tumors, Kaposi sarcoma, primary and recurrent nonmelanoma skin cancers, and in well-selected patients mucosal oropharyngeal cancers. Emerging applications include skin metastases from visceral or hematological malignancies, vulvar cancer, certain benign skin lesions, and the combination of ECT with systemic immunotherapy. Thanks to the technical developments, the new ECT indications are deep-seated tumors, including bone metastases, liver malignancies, pancreatic and prostate cancers with the use of long needle variable geometry electrodes. Herein we review the present status of ECT from the basic principles to emerging applications, and report the effi cacy of standard ECT across histotypes.]

Lege Artis Medicinae

OCTOBER 21, 2020

[Epidemiology of diabetes mellitus and diabetes-related eye complications in Hungary]

TÓTH Gábor, NÉMETH János

[Diabetes mellitus is a disease of civilization and a leading cause of blindness among people of working age in developed countries. It’s prevalence is estimated to be 9.9% in the adult population in Hungary, based on this, the estimated number of people with diabetes mellitus was 807 000 in 2015 in our country. Almost every fifth people with diabetes mellitus has some form of diabetic retinopathy in Hungary. Among diabetic persons 0.3% is blind and 0.3% has serious visual impairment due to not adequately treated diabetes mellitus. The total prevalence-based diabetes retinopathy-associated economic burden was 43.66 billion HUF in 2018 in our country. The two major cost drivers were anti-VEGF injections and vitrectomies; they covered almost the four-fifths of the total cost among people with diabetes mellitus. We have to emphasize the importance of prevention, healthy nutrition and frequent sport activity in the fight against diabetes mellitus and overweight. With at least annually performed eye examinations in people with diabetes mellitus and timely treatment of diabetic retinopathy, visual impairment and blindness due to complications of diabetes mellitus can be prevented. ]

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.]

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

JULY 01, 2020

[Treatment of hypercholesterolemia in the elderly]

BARNA István

[The percentage of population aged ≥65 years is mounting worldwide, among them those over 75 years is also growing. Athe­ro­scle­rosis is one of the most important and common disorder in the elderly responsible primarily for premature death and cognitive declining and impaired quality of life. Adequate lipid lowering therapy can decrease the risk of cardiovascular events – the main cause behind mortality – can extend life expectancy and improve the quality of life of patients. Effect of dietary treatment on cardiovascular risk reduction is as beneficial as in the younger populations. Regular physical activity reduces the risk of cardiovascular and overall mortality by 26% in males and 20% in females aged ≥65 years. If the medical history is negative for vascu­lar disorders, statin administration as a primary prevention is indicated for patients 65>years. In the population aged 75≥years individual benefit/risk assessment is needed before statin administration. Larger risk reduction can be achieved between 65-75 years than in subjects over 75 years. Concerning secondary prevention, statin treatment is of pre-eminent significance, and its administration is evidence-based in the elderly. For achieving the lipid goals, combined therapy with statin and ezetimibe is recommended in the primary as well as secondary cardiovascular prevention. ]

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.]

Lege Artis Medicinae

JULY 01, 2020

[Suicide endangering elderly people: risk factors, prevention and care]

BARACZKA Krisztina

[According to the data of the Hungarian Central Statistical Office (HCSO), the Hungarian citizens aged over 65 represented in 2001 11.8%, 2011 13.2% and 2019 19.3% of the total population. Providing services for aging (>60 years), aged (>75 years), very old (>90 years) and Matusalem (>100 years) individuals burdens heavily the health system and the socio-economic sector. Maintaining these people’s physical and mental health and self-perceived well-being is a pre-eminently important task. According to the World Health Organization (WHO) statistics based on data providing countries, the number of suicides committed in the population aged 60-79 has risen approximately by 21% between 1987 and 2006. The suicide rate in Hungary has decreased steadily and significantly since 1980 (4809 in 1980, 1656 in 2018, i.e. a decrease of 66%). Thus since 2018, Hungary is not among the top three countries in Europe and the top 15 in the world. However, the number of completed suicides and suicide attempts remains high and shows rising tendency in the elderly. Preventing suicide, exploring the risk factors and caring patients after attempted suicide we need to analyse thoroughly and disseminate widely the results of the recent researches. In this study, we re­viewed international and domestic literature data to find answers primarily to prevention issues. ]

Hypertension and nephrology

JUNE 24, 2020

[Not all young, athletic university students have optimal blood pressure. Results of the May 2019 Measurement Month (MMM19)]

PATÓ Anna, NÉMETH Zoltán, JÁRAI Zoltán, KOLLER Ákos

[For about 100 years, it has been known that persistently high blood pressure (hypertension) is the leading cause of cardiovascular disease deaths, such as major risk factors for heart failure, myocardial infarction, stroke, kidney and eye disease. Unfortunately, one of the characteristics of hypertension is that it remains undetected for a long time until damage to one or more organs has already occurred. Therefore, it is very important that systemic blood pressure is monitored from time to time, especially above 45 years of age. The prevalence of hypertension is more than 35% in the Hungarian population. Recent data have pointed out that hypertension may occur at a younger age, although at a lower frequency. Our studies were conducted in the context of the May 2019 Measurement Month (MMM19), an international campaign that draws attention to hypertension and the lack of systematic screening at population level. We hypothesized that hypertension may occur in young, apparently healthy university students. The studies were conducted among students of the University of Physical Education (n = 33; 25 males, 8 females). The mean age was 24.3 years (20–34 years). To measure blood pressure, an automatic blood pressure monitor (Omron MIT5) was used, placed on individuals’ upper arms, as specified in the guidelines, in a relaxed, sitting position. The measurements were repeated three times at one-minute intervals and the average of the three measurements was statistically analyzed. Blood pressure values (mean ± SEM, averaged over 3 measurements) in the student population were systolic 121.9 ± 14.4 mmHg, diastolic 75.1 ± 9.1 mmHg, mean 90.7 ± 10.9 mmHg, and heart rate: 46.8 ± 5.3 mmHg. Although mean blood pressure was within the normal range, higher values were also found in some individuals. Systolic blood pressure fell by 33% due to elevated normal blood pressure, respectively of Grade 1 hypertension. These data confirmed our hypothesis that hypertension may occur at a young age, despite the fact that members of the study population exercise regularly, which is an important preventive factor in the development of cardiovascular disease. These results underscore the importance of regular blood pressure measurement in adolescents, which may reduce the global spread of hypertension and prevent the development of a number of cardiovascular diseases, including stroke, heart attack, renal failure and mental decline.]

Clinical Neuroscience

MAY 30, 2020

[The long-term follow-up of enzyme replacement treatment in late onset Pompe disease]

MOLNÁR Mária Judit, BORSOS Beáta, VÁRDI Visy Katalin, GROSZ Zoltán, SEBÕK Ágnes, DÉZSI Lívia, ALMÁSSY Zsuzsanna, KERÉNYI Levente, JOBBÁGY Zita, JÁVOR László, BIDLÓ Judit

[Pompe disease (PD) is a rare lysosomal disease caused by the deficient activity of acid alpha-glucosidase (GAA) enzyme due to mutations in the GAA gene. The enzymatic deficiency leads to the accumulation of glycogen within the lysosomes. Clinically, the disease has been classically classified in infantile and childhood/adult forms. Presently cc. close to 600 mutations distributed throughout the whole gene have been reported. The c.-32-13T>G splice mutation that is very common in patients of Caucasian origin affected by the childhood/adult form of the disease, with an allelic frequency close to 70%. Enzyme replacement treatment (ERT) is available for the patients with Pompe disease (Myozyme). In this paper, we are presenting the long term follow up of 13 adult onset cases treated more than 5 years. The longest follow up was 15 years. To evaluate the treatment efficacy, the 6 minutes walking test (6MWT) and the respiratory functions were monitored annually. The analysis revealed that at the beginning of ERT for 3-4 years the 6MWT had been generally increasing, then it declined, and after 10 years it was lower in 77% of the cases than it had been at the start of the treatment. In 23% of the cases the 6MWT increased during the follow up time. Only one of the patients become wheelchair dependent during the follow-up period. The respiratory function showed similar results especially in supine position. A high degree of variability was observed among patients in their responses to the treatment, which only partially associated with the antibody titer against the therapeutic protein. The efficacy of the ERT was associated with the type of the disease causing mutation, the baseline status of the disease, the lifestyle and the diet of the patient. The long-term follow up of the patients with innovative orphan drugs is necessary to really understand the value of the treatment and the need of the patients.]