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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.]

Clinical Neuroscience

NOVEMBER 30, 2020

[The connection between the socioeconomic status and stroke in Budapest]


[The well-known gap bet­ween stroke mortality of Eastern and Western Euro­pean countries may reflect the effect of socioeconomic diffe­rences. Such a gap may be present between neighborhoods of different wealth within one city. We set forth to compare age distribution, incidence, case fatality, mortality, and risk factor profile of stroke patients of the poorest (District 8) and wealthiest (District 12) districts of Budapest. We synthesize the results of our former comparative epidemiological investigations focusing on the association of socioeconomic background and features of stroke in two districts of the capital city of Hungary. The “Budapest District 8–12 project” pointed out the younger age of stroke patients of the poorer district, and established that the prevalence of smoking, alcohol-consumption, and untreated hypertension is also higher in District 8. The “Six Years in Two Districts” project involving 4779 patients with a 10-year follow-up revealed higher incidence, case fatality and mortality of stroke in the less wealthy district. The younger patients of the poorer region show higher risk-factor prevalence, die younger and their fatality grows faster during long-term follow-up. The higher prevalence of risk factors and the higher fatality of the younger age groups in the socioeconomically deprived district reflect the higher vulnerability of the population in District 8. The missing link between poverty and stroke outcome seems to be lifestyle risk-factors and lack of adherence to primary preventive efforts. Public health campaigns on stroke prevention should focus on the young generation of socioeconomi­cally deprived neighborhoods. ]

Hypertension and nephrology

SEPTEMBER 30, 2020

[Non-pharmacological treatment of hypertension and reducing cardiovascular risk in general practitioners’ clusters]


[Hypertension and cardiovascular diseases are major public health issues. In their treatment non-pharmacological methods have a role in every case either alone or as a complement. Patient adherence is a key factor. The role of primary care is very important in the management and with general practitioners’ cluster model and with the involvement of new primary care professionals (for example: dietetitian, physiotherapist) the opportunities are expanding. In the A GP Cluster and in the Marosmenti GP Cluster the analysis of the patients’ results who participated in an individual health status examination, in dietetic and in physiotherapy services. Assessing the professionals’ attitudes towards GP cluster model. In the A GP Cluster 2409 people, in the Marosmenti GP Cluster 1826 people participated in an individual health status examination. 14.6% and 19.9% of the participants were under the age of 18. 58.9% and 60.7% of the participants over the age of 18 were female. 1083 and 232 patients used physiotherapy services, 147 and 187 people used dietetic services. The age distribution of the individual health status examinations is correspond to the Hungarian age pyramid. In addition to the preventive approach came into view the community based local health care services. The GP cluster model was welcomed by the patients, the physiotherapy was more popular than dietetic among them. All professionals of the GP clusters had a positive opinion of the professional work done in the project. Conclusion: There is a demand both from the patients and the healthcare professionals for the GP cluster concept. The establishing of an appropriate monitoring system and creating long-term, sustainable operating conditions are essential for achieving lasting social health gains. ]

Hypertension and nephrology

SEPTEMBER 30, 2020

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


[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.]

Hypertension and nephrology

SEPTEMBER 30, 2020

[Treatment and care of hypertensive patients during and after the Covid-19 pandemic. Possibilities and effectiveness of telemedicine]


[The course and outcome of an pandemic caused by coronaviruses are determined by many factors, such as the strength and dose of the infectious virus, the immune system of the affected individual, the underlying diseases, the speed of virus spread, age and environmental factors and methods of control. In old age, there is a significantly higher risk of developing severe cases and fatalities. The rate of loss of life is particularly high in social care and nursing homes. Hypertension as the underlying disease is the most common cause of death, but hypertension alone is not an independence risk factor, but the main reason is the co-morbidities and complications associated with viral infection. In the epidemic situation, the treatment and care of hypertensive patients poses special challenges for health and active primary and specialist care workers and, of course, for hypertonologists. The Hungarian Society of Hypertension expressed its opinions and recommendations to patients living at home and to doctors performing treatment and care during the Covid-19 virus epidemic and summarized the decision-making possibilities derived from the data obtained during the telemedicine consultation. We would like to present the details of the possibilities provided by telemedicine, the practical possibilities and advantages of the different methods of teleconsultation, and the models that can be implemented in a domestic environment. We have taken into account international experience to date, the new e-health strategy for chronic, non-communicable diseases and the WHO concept. Telemedicine, continuous teleconsultation ensures an optimal relationship between the patient and the doctor, increases the patient’s sense of security, improves drug adherence. The doctor receives reliable data about the patient’s condition and can send him instructions as well as information. The development of a harmonious balance between personal contact and telecommunications already shows the future, and the application of these methods must be developed in the epidemic-free period as well. Previous international (TASMINH-4, HOMED-BP etc.) and domestic (CONADPER-HU) studies have proved that telemonitoring of hypertensive patients can be successfully solved, improves patients’ drug adherence, increases the target blood pressure achievement rate and at the same time the patient will be the active part of the treatment. The method is especially useful in rural settlements without a doctor. Telemedicine monitoring of elderly and multimorbid patients is especially useful in social institutions and nursing homes. It is solved the continuous control of vital functions, ensures continuity of contact with the supervising physician and in urgent cases, allows for rapid intervention. Telemedicine is also of great importance due to the lack of human resources, as many things can be solved with such technology, there are no need so many personal encounters. In addition to influencing the course of this pandemic, it also plays an important role in efficiency, headcount, management and “convenience” in general practice and in all formes of medicine. The proposed models can not only be applied in an epidemic situation, but should continue to be part of everyday health work in future.]

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.

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.]

Hypertension and nephrology

JUNE 24, 2020

[Systolic and diastolic blood pressure by height, BMI, gender and age between 14 and 18 years of age]


[The aim of the screening program was to investigate blood pressure levels in different ages according to obesity. Blood pressure, heart rate, body composition, bodyweight, height and BMI were assessed. 2202 adolescent (1326 girls, 876 boys) participated in the screening program. The mean systolic blood pressure of all screened adolescents was 126.34 ± 12.55 mmHg. Boy/girl values were 131.87 ± 13.59/117.49 ± 5.69 mmHg, p < 0.001. The mean diastolic blood pressure of all screened adolescents was 71.86 ± 8.74 mmHg. Boy/girl values were 72.61 ± 9.17/66.69 ± 5.04 mmHg, p < 0.001. The 50%, 90%, 95%, and 99% thresholds and cases for systolic, diastolic blood pressure, and the BMI and BodyFluid thresholds, detailed for 14–18 year olds, girls and boys, are tabulated. Systolic blood pressure (SBP) was over 99% in 12 girls (14- year-olds), 39 (15), 42 (16), 33 (17), 5 (18) to height. SBP was over 99% in 17 boys (14-year-olds), 73 (15), 100 (16), 33 (17), 5 (18) to height. It is emphasized that systolic blood pressure (SBP) is > 99% in 12 girls (14 years), 39 (15), 42 (16), 33 (17), 5 (18) to body height. SBP > 99% for 17 boys (14 years), 73 (15), 100 (16), 33 (17), 5 (18) to body height. Elevated diastolic values were associated with elevated systolic values, but less occurred. The percentage of high blood pressure was more frequent among boys and girls who were in the overweight group (58.6% and 18.6%). Normal blood pressure is higher in overweight and obese adolescents and is a significant risk factor for developing high blood pressure in young adulthood.]

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

JULY 30, 2020

[Comparative analysis of the full and shortened versions of the Oldenburg Burnout Inventory]

ÁDÁM Szilvia, DOMBRÁDI Viktor, MÉSZÁROS Veronika, BÁNYAI Gábor, NISTOR Anikó, BÍRÓ Klára

[Background – The two free-to-use versions of the Oldenburg Burnout Inventory (OLBI) have been increasingly utilised to assess the prevalence of burnout among human service workers. The OLBI has been developed to overcome some of the psychometric and conceptual limitations of the Maslach Burnout Inventory, the gold standard of burnout measures. There is a lack of data on the structural validity of the Mini Oldenburg Burnout Inventory and the Oldenburg Burnout Inventory in Hungary. Purpose – To assess the structural validity of the Hungarian versions of the Oldenburg Burnout Inventory and the Mini-Oldenburg Burnout Inventory. Methods – We enrolled 564 participants (196 healthcare workers, 104 nurses and 264 clinicians) in three cross-sectional surveys. In our analysis we assessed the construct validity of the instruments using confirmatory factor analysis and internal consistency using coefficient Cronbach’s α. Results – We confirmed the two-dimensional structure (exhaustion and disengagement) of the Mini-Oldenburg Inventory and a shortened version of the Oldenburg Burnout Inventory Internal consistency coefficient confirmed the reliability of the instruments. The burnout appeared more than a 50 percent of the participants in every subsample. The prevalence of exhaustion was above 54.5% in each of the subsamples and the proportion of disengaged clinicians was particularly high (92%). Conclusions – Our findings provide support for the construct validity and reliability of the Hungarian versions of the Mini-Oldenburg Burnout Inventory and a shortened version of the Oldenburg Burnout Inventory in the assessment of burnout among clinicians and nurses in Hungary.]