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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

hirdetés

[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.]

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]

MODEST D. P., PANT S., SARTORE-BIANCHI A.

[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, 2021

[The questions of the treatment of Parkinson’s disease]

NAGY Ferenc

[Despite the continuous development of diagnosis and treatment of patients with Parkinson’s disease and the arrival of new therapeutic options in recent years the treatment and care of people with Parkinson’s disease especially in the advanced stage remains a major challenge for neurologists specialized in movement disorders. The treatment of Parkinson’s disease is adversely affected by several factors: the disease progresses relentlessly, the symptoms and rate of progression, other concomitant non-motor symptoms, and the appearance of complications caused by treatment show great heterogeneity. Based on all these factors it is difficult to develop and apply a uniform routine therapeutic guideline. This summary seeks to shed light on aspects of the treatment of Parkinson’s disease particularly in advanced-stage cases drawing on data from a professional college recommendation and the literature.]

Clinical Oncology

FEBRUARY 28, 2020

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

SIPŐCZ István

[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.]

Lege Artis Medicinae

JUNE 07, 2021

[Negative pressure wound care while covid-19 pandemic: treatment of necrotizing fasciitis and retroperitoneal abscess]

ZÁDORI Gergely, SUSÁN Zsolt, TÓTH Csaba Zsigmond, TÓTH Dezső, SZENTKERESZTY Zsolt

[Necrotizing fasciitis is a rare and high mortality condition. Most commonly it is spreading in the extremi­ties, abdominal wall soft tissues and perineal region, but occurs rarely in the retroperitoneal space too. Primary treatment is debridement with administered antibiotics, supported by negative pressure wound care. The present case report concerns a successful treatment of an extensive necrotizing fasciitis spreading from the hip region and ending up in a retroperitoneal abscess. A gradually increasing, painful, ulcerated swelling developed in the patient’s right hip region. On the first examination, elevated laboratory markers of inflammation were identified while the necrotizing lesion raised concerns of sarcomatic background. Initially, we started antibiotics and took tissue samples. The prompt CT scan confirmed a large abscess complex involving also the retroperitoneal space. The surgical exploration verified a typical necrotizing fasciitis and after removing debridement negative pressure wound care was started. After 14 days of this treatment the patient recovered successfully. Negative pressure wound therapy is pivotal in the treatment of necrotizing fasciitis. The number of wound dressings and of medical staff – patient contacts can be significantly reduced by this me­thod. It has a major advantage in the COVID-19 pandemic, since minimalizing close contacts is of vital importance in controlling the spread of the virus.]

Hypertension and nephrology

JUNE 24, 2021

[The main directions of treatment of obesity are described in VIII. Hungarian In the light of the Cardiovascular Consensus Conference]

SIMONYI Gábor, BEDROS J. Róbert

[The treatment of obesity is a complex process, the elements of which are lifestyle change (diet and exercise), psychic driving, medication and need in case of surgical treatment. The Hungarian Society of Obesitology and Movement Therapy the first half year of the weight loss program is low in carbs and elevated suggests a protein-rich diet. When designing physical activity, dynamic, aerobic (eg walking, walking, jogging, swimming, cycling, etc.) are recommended. In drug therapy, orlistat, naltrexone / bupropion, is fixed combination and liraglutide play a role. Bariatric surgery they are currently most effective in the short- and long-term treatment of obesity.]

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.]