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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 Neuroscience

MARCH 30, 2021

[Consensus statement of the Hungarian Clinical Neurogenic Society about the therapy of adult SMA patients]

BOCZÁN Judit, KLIVÉNYI Péter, KÁLMÁN Bernadette, SZÉLL Márta, KARCAGI Veronika, ZÁDORI Dénes, MOLNÁR Mária Judit

[Background – Spinal muscular atrophy (SMA) is an autosomal recessive, progressive neuromuscular disorder resulting in a loss of lower motoneurons. Recently, new disease-modifying treatments (two drugs for splicing modification of SMN2 and one for SMN1 gene replacement) have become available. Purpose – The new drugs change the progression of SMA with neonatal and childhood onset. Increasing amount of data are available about the effects of these drugs in adult patients with SMA. In this article, we summarize the available data of new SMA therapies in adult patients. Methods – Members of the Executive Committee of the Hungarian Clinical Neurogenetic Society surveyed the literature for palliative treatments, randomized controlled trials, and retrospective and prospective studies using disease modifying therapies in adult patients with SMA. Patients – We evaluated the outcomes of studies focused on treatments of adult patients mainly with SMA II and III. In this paper, we present our consensus statement in nine points covering palliative care, technical, medical and safety considerations, patient selection, and long-term monitoring of adult patients with SMA. This consensus statement aims to support the most efficient management of adult patients with SMA, and provides information about treatment efficacy and safety to be considered during personalized therapy. It also highlights open questions needed to be answered in future. Using this recommendation in clinical practice can result in optimization of therapy.]

Clinical Oncology

DECEMBER 10, 2018

[PI3K–AKT–mTOR pathway as a therapeutic target]

KOPPER László

[The PI3K-AKT-mTOR is one of the most busy signalling pathway, accepting and sending the message to the effector compartment. The pathway is very complex with activators (see the name), and inhibitors, as PTEN. Depending of the cell type this pathway participates in almost all functions of a given cell. The members of the pathway may have genetic failures, as a consequence, the risk for the development of different diseases, including cancer is high. Therefore it is logical to produce drugs to inhibit the dysregulated function. Unfortunately, despite the promising preclinical effectivity, so far only 4 drugs can be used to treat cancer patients. There are some hypothesis for the in effectivity, e.g. no useful marker for patient selection, high toxicity, false drivers for targeting. What is sure, combination therapy is much better than monotherapy]

Clinical Oncology

DECEMBER 05, 2017

[Protontherapy]

LAKOSI Ferenc, HADJIEV Janaki, CSELIK Zsolt, GULYBÁN Ákos

[Radiotherapy with protons is a promising technology in the fi eld of modern radiation oncology. From a physical point of view, radiotherapy with protons has important advantages compared to the currently used photons due to its unique energy absorption profi le, which may result in a better local tumor control and reduced radiation-induced side effects. Increasing number of patients is treated with protons and carbon-ions. Our report aim to present the current status of proton radiotherapy including physical and technological aspects, standard and non-standard indications, ongoing clinical trials and the proton vs. photon debate in terms of patient selection.]

Clinical Neuroscience

JANUARY 30, 2019

[Selection of the optimal device-aided therapy in Parkinson’s disease]

KOVÁCS Norbert, ASCHERMANN Zsuzsanna, JUHÁSZ Annamária, HARMAT Márk, PINTÉR Dávid, JANSZKY József

[For the treatment of advanced Parkinson’s disease the deep brain stimulation (DBS) and the levodopa/carbidopa intestinal gel (LCIG) therapies are available in Hungary. Although they may have similar impact on the health-related quality of life and disabilities associated with the disease, they have different indications, and inclusion- and exclusion criteria. Consequently, the patient population treated with DBS and LCIG may be different. In the present review, the authors try to help the process of selection of the optimal device-aided therapy for the patients with advanced Parkinson’s disease. ]

Clinical Neuroscience

NOVEMBER 30, 2018

[Comparison of subthalamic nucleus planning coordinates in 1Tesla and 3Tesla MRI for deep brain stimulation targeting ]

JUHÁSZ Annamária, KOVÁCS Norbert, PERLAKI Gábor, BÜKI András, KOMOLY Sámuel, KÖVÉR Ferenc, BALÁS István

[Backgroud - Deep brain stimulation (DBS) involves placing electrodes within specific deep brain nuclei. For movement disorders the most common indications are tremors, Parkinsons disease and dystonias. Surgeons mostly employ MR imaging for preoperative target selection. MR field geometrical distortion may contribute to target-selection error in the MR scan which can contribute to error in electrode placement. Methods - In this paper we compared the STN target planning coordinates in six parkinsonian DBS patients. Each patient underwent target planning in 1T and 3T MRI. We statistically compared and analysed the target-, and the fiducial coordinates in two different magnetic fileds. Results - The target coordinates showed no significant differences (Mann-Whitney test, p > 0.05), however we found significant difference in fiducial coordinates (p < 0.01), in 3T MRI it was more pronounced (mean ± SD: 0.8 ± 0.3 mm) comparing to 1T (mean ± SD: 0.4 ± 0.2 mm). Conclusion - Preliminary results showed no significant differences in planning of target coordinates comparing 1T to 3T magnetic fields.]

Clinical Oncology

FEBRUARY 10, 2018

[The role of early clinical studies in oncology]

KERPEL-FRONIUS Sándor

[Although the basic theory of the early development of different drug groups is identical, due to their various pharmacological characteristics the design of the studies, the starting safe dose and the selection of the pharmacologic and therapeutic end-points show signifi cant differences. The development process of drugs is usually divided into two functionally different parts, the learning and the confi rming phases, respectively. The aim of the fi rst part is the description of the suggested targets, the mechanism of action in humans and the characterization of the drug-linked biomarkers. This section contains the microdose (phase 0), phase I and II studies. The end-point of this part is the proof of the underlying concept which was developed on the basis of the non-clinical studies. According to the internationally accepted terminology, this strategically important point is called the Proof of Concept (POC). Upon POC it has to be decided whether the drug-candidate possesses those qualities which make it worthwhile to perform human phase III studies, treating the statistically required number of patients for proving the good therapeutic effi cacy and safety of the drug. This section of the drug development is called the confi rmatory phase. The use of highly sophisticated technology opened the possibility to apply microdoses in humans for studying the pharmacokinetics and pharmacodynamics of new drugs as well as the characteristics of human biomarkers at very low, harmless drug doses. This approach made possible to draw important conclusions on the usefulness of biomarkers for the clinical practice even following the fi rst drug-application. The planning of phases I and II studies, the calculation of the applicable doses, the selection of the pharmacologic and therapeutic end-points, the use of biomarkers, are all based on the concept of translational medicine and are essentially dependent on the results obtained both in animal experiments and human microdose studies.]

Hypertension and nephrology

SEPTEMBER 10, 2019

[Hungarian Hypertension Registry. Different methods and effects of increasing physician-patient cooperation on target blood pressure]

SZEGEDI János, KÉKES Ede, KISS István

[The life expectancy, the mortality and the development of complications of hypertensive patients are fundamentally influenced by the treatment, the effectiveness of care and physician-patient cooperation, the achievement of target blood pressure. Based on the database of the Hungarian Hypertonia Registry, we present three examples of the effect of different solutions for physician-patient cooperation on increasing the blood pressure target. During the two years between 2005 and 2007, we used a complex, versatile method of increasing the patient’s adherence in treated hypertensive patients (17,114 males and 21,772 women), with information, education, home-blood pressure diary, and continuous, regular physician- patient communication (sms, green phone line, website). The target blood pressure was significantly increased from 38.8% to 43.9%, and the rate of growth was higher in women. The increase was also significant in the elderly (over 70 years). In the first quarter of 2011, we launched a wide-ranging education and patient support campaign for 28,018 hypertensive patients under the ‘Everywhere Good, Best Home!’ subprogram for promoting of home blood pressure measurement and its use in therapy. 81.3% of the patients had completed the diaries under ther observation period, the full completion of the diaries was 91.3%. At the end of the third month, the target blood pressure of 135/85 mmHg for HBPM increased from baseline 21.2% to 48.8%. Growth was significant (P <0.001). In the year 2015-2016 we started a one-year, multicentric, prospective, observational study, in which 7735 patients aged 18-64 years were included from the database of Hungarian Hypertension Registry. In the non-active group (3313 people), treated hypertensive patients were controlled according to the traditional care program so far, while the active group members (4422) participated in an intensive care program with telemedicine (smart phone application) and other helping opportunities. The control was done at the end of 3, 6, 9, and 12 months after the start. In the active group, blood pressure dier was done by smart phone and every month, in the non-active group, paper logging was done every 3 months. In the active group, the blood pressure dieries were filled with smart phone every month and in nonactive group the paper dieries only every 3 months. Patient adherence was high in both groups (around 70%) and in the active group was greater than in the nonactive group. Target blood pressure (<140/90 mmHg) in the active group increased from 53.8% to 73.4% and in the non-active group from 49.9% to 68.1%. Studies have shown that patient interaction is determined by good communication between the care team and the patient, success of home blood pressure monitoring. The communicative ability of the care team (physician-nurse pharmacist) greatly influences the achievement of the therapeutic target. Modern telecommunications is another useful option.]

Clinical Oncology

AUGUST 28, 2020

[Complex treatment of head and neck cancers – overview]

DÁNOS Kornél, TAMÁS László

[Treatment of head and neck squamous cell carcinomas (HNSCC) is exceptionally complex, requiring the close cooperation of the head and neck surgeon, radiation oncologist and medical oncologist. Excellent tumor control should be our primary goal, however, the selection of treatment should not only be guided by oncologic radicality but by the need of satisfactory quality of life (as most local therapies affect respiratory, swallowing and/or speech function), too. Based on the appropriate diagnostic workup, these cancers are classifi ed into early, locoregionally advanced or recurrent/metastatic stages. Each category requires different treatment modalities, further complicated by the localization of the primary tumor and its metastases, performance status of the patient, comorbidities, and the biology of the lesion. In the present review, the authors summarize the basics of the therapy of head and neck cancers.]

Lege Artis Medicinae

JULY 20, 2019

[Severe polymyositis associated with multiplex pulmonary abscesses]

SZABÓ Katalin, VINCZE Anett, NAGY-VINCZE Melinda, DANKÓ Katalin, GRIGER Zoltán

[INTRODUCTION – Idiopathic inflammatory myopathies are heterogeneous autoimmune diseases characterized by immune mediated inflammation of the skeletal muscles. CASE REPORT – A case of a 62-year-old male patient with severe proximal muscle weakness, elevated creatine kinase and swallowing difficulity is presented. Electromyography showed myogenic pattern, thus probable polymyositis was diagnosed. Radiological examination has confirmed bilateral multiplex lung lesions, which were caused by the possibility of tumor, tuberculosis, vasculitis and abscess as well. The condition of the patient deteriorated, nasogastric feeding, high dose steroid treatment was initiated, which reduced the patient's creatinine kinase values, but muscle strength was not changed. Based on the results of various investigations, the condition of the patient was finally confirmed by the development of myositis, resulting dysphagia, chronic aspiration, and multiplex lung abscess. Antibiotic therapy, steroid treatment was continued and finally intravenous immunoglobulin treatment was administered. The condition of the patient gradually improved, the swallowing dysfunction disappeared, and the lung abscesses were resolved. As a result of physiotherapy and rehabilitation treatment, the patient could walk again. CONCLUSIONS – Nasogastric feeding is recommended to prevent aspiration in the case of myositis-associated dysphagia. In case of steroid refractory therapy, the use of intravenous immunoglobulin may be effective. ]