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Lege Artis Medicinae

APRIL 18, 2020

[Digitally-assisted treatment planning in precision oncology]


[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. ]

Lege Artis Medicinae

SEPTEMBER 30, 2020

[Analysis of factors influencing the efficacy of Hungarian acute cardiac care]


[Despite the modern invasive acute cardiac care available for all, as opposed to short-term mortality, the long-term mortality of Hungarian myocardial infarction patients exceeds significantly those of European patients getting similar treatment. In order to change this situation, it is necessary to assess and analyse exactly the factors behind. While analysing retrospectively the data of Hungarian acute myocardial infarction patients, we identified the influencing factors of short- and long-term mortality. This study processed data from 2003 to the present days from a number of registries (Heart- and Vascular Center of Semmelweis University VMAJOR I and VMAJOR II registry, Stent for Life I and II Programs of the European Society of Cardiology, National Public Health Service’s registry about Cardiac Care in Central Hungary, Budapest Modell database). According to our detailed examination, the proportion of primary per­cutaneous coronary intervention in ST-segment elevation myocardial infarction is at Western-European level, however the invasive treatment of acute coronary attack patients with Non-ST segment myocardial infarction is below the required. The so-cal­led hesitation span of Hungarian pa­tients with ST-segment myocardial infarc­tion is substantially longer than that of neighbouring countries thus the average cardiovascular risk of relevant Hungarian patients is significantly higher than those of the GRACE Register’s population. Based on our results a complex strategy can be developed which may have impact also on strategic health­care decisions in order to reduce the long-term mortality of patients surviving myocardial infarction.]

Lege Artis Medicinae

MARCH 10, 2020

[Primary care strategy of antihypertensive treatment of very elderly and frail patients]

TORZSA Péter, KALABAY László, CSATLÓS Dalma, HARGITTAY Csenge, MÁRKUS Bernadett, MOHOS András, SZIGETI Mátyás, FERENCI Tamás, MARJOLEIN Verschoor, ROZSNYAI Zsofia, JACOBIJN Gussekloo, ROSALINDE K. E. Poortvliet, SVEN Streit

[BACKGROUND - When treating very el­der­ly and frail hypertensive patients, there have to be taken in account the general health condition and frailty of patients, the present cardiovascular diseases (CVD) and values of the systolic blood pressure (SBP). Goals - In a clinical study performed in 29 countries, we aimed to analyse differences in practical antihypertensive therapy of family doctors among patients older than 80 years; further we sought to answer how much was influenced their therapeutic choice by frailty of the old age. The other goal of our study was to compare Hungarian versus international outcomes. Methodology - As part of an online survey, family practitioners had to decide about necessity of starting antihypertensive treatment among very elderly patients according to different patterns of frailty, SBP and CVD. The ratio of specific cases with positive treatment decision of family practitioners was compared in all 29 countries. We used a logistic mixed model analysis to multivariately model the role of frailty. Results - 2543 family practitioners participated in the cross-national study; 52% were female; 51% practised in urban environment. In 61% of practices, there was the ratio higher than 10% of very elderly patients. Hungary participated with 247 family practitioners in the study; 52.3% were female; 63.1% practised in urban environment. In 48.8% of practices the ratio of very elderly patients was higher than 10%. In 24 out of the 29 countries (83%), frailty was associated with GPs’ negative decision about starting treatment even after adjustment for SBP, CVD, and GP characteristics (odds ratio [OR 0.53]), 95% CI: 0.48-0.59; ORs per country 0.11-1.78). The lowest treatment ratio was in the Netherlands (34.2%; 95% CI: 32.0-36.5%) and the highest one in Ukraine (88.3%; 95% CI: 85.3-90.9%). In Hungary’s treatment ratio ranged 50-59%. This country ranked on the 27th place since Hungarian family practitioners chose rather to start antihypertensive treatment despite the frailty of the patient (OR=1.16; 95% CI: 0.85-1.59). Hungarian family practitioners started pharmacotherapy of elderly patients more frequently if they were males (OR= 1.45; 95% CI: 0.81-2.61), were working in their practice for less than 5 years (OR=2.41; 94% CI: 0.51-11.38), and if they had many patients aged over 80 years in their practice (OR=2.18; 95% CI: 0.70-6.80), however these differences were sta­­tistically not significant. Among Hun­ga­rian family practitioners starting therapy was significantly influen­ced by cardiovascular disease (OR=3.71; 95% CI: 2.64-5.23) and a SBP over 160 mmHg (OR=190.39; 95% CI: 106.83-339.28). Conclusions - In our study, there was significant difference between countries in starting antihypertensive treatment for very elderly patients. However, Hungary was among the countries where family practitioners preferred to treat their frail patients. The patients’ frailty did not have any impact on starting the therapy; rather cardiovascular disease and a SBP over 160 mmHg decided. It is an important message of the study that there is continuous need to educate family practitioners and trainees about the treatment of frail, elderly hypertensive patients.]

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

MAY 30, 2018

Retrospective comparison of efficacy of levetiracetam and lacosamide add-on treatments in patients with partial onset seizure

ACAR Türkan, ARAS Guzey Yesim

Objective - The study aims to retrospectively compare the efficacy of lacosamide (LCS) and levetiracetam (LEV) in add-on treatment in patients with partial-onset epilepsy. Material and method - Patients who have been followed-up for at least one year due to diagnosis of partial epilepsy between September 2014 and December 2017 and who had no seizure control, despite using at least two antiepileptic monotherapies, and therefore undergone LEV or LCS add-on treatment were retrospectively reviewed. Of the patients, total number of seizures and seizure control rates 6 months before and 3 and 6 months after the add-on treatment were compared. Results - There was no statistically significant difference between the 30 patients in the LEV group (12 females, 18 males, mean age 29.7±6.6) and 28 patients in the LCS group (12 females, 16 males, mean age 28.2±6.4) in terms of age, gender and the duration of illness. When the LEV and LCS groups were evaluated separately, the mean number of seizures within 3 and 6 months after the add- on treatment were significantly lower than the mean number of seizures in the last 6 months before the add-on treatment (p<0.005 and p<0.005 respectively). There was no statistically significant difference between the two groups when compared with each other in terms of the rate of decrease in number of seizures and seizure control before and after the add-on treatment (p=0.445 and p=0.238, respectively). Conclusion - LCS appears to be as effective as the currently well-established LEV in the treatment of partial onset seizures. No comparative study was found in the literature similar to this subject matter. There is a need for prospective studies for the comparison of the efficacies of these two drugs.

Clinical Oncology

FEBRUARY 28, 2020

[The treatment of the locally advanced and the metastatic gastric cancer]


[Although signifi cant progress has been made in the treatment of stomach cancer recently, survival results are still quite modest. The purpose of this overview is to take a look into the history of the treatment of locally advanced and metastatic stomach cancer and to present the current treatment standards. It focuses on recent changes in perioperative treatment, as well as the changing of treatment of metastatic patients. The use of multiple line of palliative chemotherapy and the place of the available targeted treatments in metastatic tumours will be analysed in detail. The increasing use and the future possibilities of immunocheckpoint inhibitors will also be discussed. Molecular subtypes of gastric cancer are also mentioned as possible indicators of the choice of therapy. Finally, it intends to give therapeutic proposals to make recommendations to treat the disease taking into account the opportunities in Hungary.]

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.]

Hypertension and nephrology

FEBRUARY 24, 2021

[Prevalence and treatment of hypertension in patients with newly diagnosed familial hypercholesterolemia]

NÁDRÓ Bíborka, DIÓSZEGI Ágnes, KOVÁCS Beáta, PARAGH György, PÁLL Dénes, HARANGI Mariann

[Familial hypercholesterolemia (FH) is an inherited defect of cholesterol metabolism characterized by high plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels and premature cardiovascular disease risk. Prevalence of hypertension in FH is not clarified, but its appearance is independent risk factor for the development of cardiovascular disease. Therefore, optimal treatment has a major priority in this high-risk population. We aimed to investigate the lipid parameters and evaluate the presence of hypertension and its treatment characteristics in 86 newly diagnosed, untreated heterozygous FH patients (27 males, 59 females, mean age 53.6±13.4 years). We diagnosed FH by using the Dutch Lipid Clinic Network criteria. The mean TC level was 8.49±1.7 mmol/l, the mean LDL-C level was 6.11±1.5 mmol/l, the mean high-density lipoprotein cholesterol (HDL-C) level was 1.62±0.5 mmol/l, while the median lipoprotein (a) level was 301 mg/l. We diagnosed 33 FH patients (38.4%) with hypertension. Beta blockers were used in 23, ACE-inhibitors in 13, ARBs in 12, calcium channel blockers in 9, and HCT in 11 cases. 11 patients was treated with monotherapy, for 10 patients double, for 11 patients triple, while for 1 patient quadruple combined antihypertensive therapy was administered. Based on our results, hypertension might be underdiagnosed in this specific patient population. Neither the types nor the combination patterns of blood pressure lowering agents are in line with current guidelines. Up to date screening and treatment of hypertension should be worth considering in this extremely high risk population with enhanced atherosclerosis.]

Clinical Oncology

FEBRUARY 28, 2020

[Non-surgical treatment of ovarian cancer]

PIKÓ Béla, LACZÓ Ibolya,, MARIK László

[The primary surgery with an optimal cytoreduction is an essential step during the treatment of the epithelial ovarian cancer because it determines the effectiveness of other therapeutic options as well. Immediately after the surgery a cytostatic infusion typically 40-42.5 degrees Celsius is pumped directly to the abdomen. During the systemic therapy the main point is the 6 months progression free survival because beyond this time the disease could be considered as platinum sensitive, inside this time as platinum refracter or resistant disease. The cytostatic treatment improved during the years from the alkylating agents through the platinum derivates to the administration of paclitaxel with several combinations of them and with more and more signifi cant results and less side effects. The most signifi cant targeted agents are the angiogenesis inhibitors (mainly the bevacizumab) and the PARP-inhibitors which prevents DNA repairs. In order to a PARP-inhibitor could be administered a platinum sensitivity is required while BRCA mutation not. Recently there are promising clinical researches with immunotherapy as well. The main benefi t of the hormonal therapy is the tolerability. Besides the signifi cant improvement in the systemic agents the role of radiotherapy is more and more decreasing, however the treatment of the whole peritoneal surface – mainly with the modern radiation techniques – could be an alternative solution for the chemotherapy. The palliative irradiation which relieve the symptoms could extend the drug-free period and the combination of radiation and chemotherapy could provide further possibilities.]

Clinical Oncology

DECEMBER 30, 2019

[Prevention and treatment of venous thromboembolism in cancer patients]

[Venous thromboembolism (VTE) is a common and severe complication of cancer. Deep vein thrombosis and pulmonary embolism are the second most common cause of death in cancer patients. Cancer, tumor-related factors as well as patient’s general condition and comorbidities are responsible for the increased risk of VTE. Chemotherapy is one of the most important risk factors for VTE, increasing incidence of VTE by 6.5-fold. In my paper, current guidelines for cancer VTE prevention and treatment are reviewed. Hospitalized patients with active tumor are at higher risk for VTE, and thrombosis prophylaxis is recommended in all cases. Extensive, routine prophylaxis for advanced cancer patients receiving chemotherapy is not recommended, but may be considered in high-risk ambulatory cancer patients (Khorana-score ≥ 3). Risk factors may change during the course of cancer disease, and the score should be continually reviewed and prophylactic treatment changed as necessary. LMWH is the recommended agent for both primary and secondary prophylaxis/treatment. Direct oral anticoagulants (DOACs) are knocking on our door, but results from further clinical trials are pending to determine their exact role.]