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Lege Artis Medicinae

DECEMBER 21, 2020

[The metamizole]

DUMELE Andreea

[Metamizole in use for almost 100 years, is reviving in our days since it has proved its efficiency and gained popularity during the past years. By its special triple effect (analgesic, antipyretic and spasmolytic) it has a wide range of indications. Among the non-opioid analgesics it is one of the most powerful painkillers. Metamizole is a prodrug, since it transforms into active metabolites within the human body. Its action mechanism is complex, not completely understood so far. Contrasted to classic non-steroidal anti-inflammatory drugs, metamizole has low anti-inflammatory effect. Its severe, but very rare side effect – i.e. the agranulocytosis - hindered its administration for years and even today it is under intense discussions. Based on international studies, it proved to be a well tolerable, safe medication. Its side effect profile differs from non-steroidal anti-inflammatory drugs, thus in NSAID contraindications it provides an excellent alternative. Its good water solubility makes metamizole suitable for both oral and parenteral administration. For its efficiency and good safety profile, metamizole has been correctly reintroduced to the supply of over-the-counter painkillers in our country.]

Lege Artis Medicinae

DECEMBER 21, 2020

[Family therapy encounters with the philosophy of dialogue – Ivan Boszormenyi-Nagy was born 100 years ago]

KELEMEN Gábor

[This paper deals with the significant therapeutic innovations of Ivan Boszormenyi-Nagy in the light of their philosophical foundations. The greatest Hungarian family therapist, Boszormenyi-Nagy’s work evolved in America. The author, referring to Bo­szormenyi-Nagy’s career, presents the phi­losophical roots of his theory. Par­ti­cu­larly Martin Buber’s philosophy of dialogue including the concept of existential guilt, violanting the justice of human order. Bo­szormenyi-Nagy, who elaborated contextual therapy and its main dimension, the ethics of fairness, assumes that family life, ethical questions of truthworthiness and res­ponsibity for the consequences of our actions are inseparable. Contextual therapy was groundbreaking in its time with the therapeutic attitude and method of multidirected partiality, and is relevant even today. This guideline, requiring to include all people with their humanity, solidarity and accountability who are potentially affected remains sound clinical unifying principle of comprehensive psychotherapeutic practice. ]

Lege Artis Medicinae

DECEMBER 21, 2020

[History of vaccine production in Hungary ]

ÓCSAI Lajos

[This study presents the complete history of the Hungarian vaccine production, partly in association with the process of fighting vaccine-preventable infectious diseases, and underlines the fact that every government actively contributed to the age-adjusted mandatory vaccination schedule of the past 140 years. It demonstrates the various achievements from the smallpox lymph production through the launch of diphtheria serum production at Phylaxia and the establishment of the National Public Health Institute (OKI) with its vaccine production and the later institutional transformation of OKI into Humán as economic corporation to its closure. Among all OKI’s vaccine production activities, this study focuses on the production of influenza vaccines, due to its international importance in the 1960s and 1970s. The vaccine production against diphtheria tetanus and pertussis stands out from Humán’s activities, and the tetanus component of this vaccine is still used in the products of a multinational vaccine manufacturer. ]

Lege Artis Medicinae

DECEMBER 21, 2020

[Risk of nonsteroidal antiinflammatory drugs. Focus on aceclofenac]

FARSANG Csaba

[Nonsteroidal antiinflammatory drugs (NSAIDs) are among the most frequently used pharmaceuticals. Nevertheless, a number of studies emphasized that NSAIDs were damaging not only the gastrointestinal (GI), but also the cardiovascular (CV) system, could increase the blood pressure, the frequency of coronary events (angina, myocardial infarction) and stroke incidence, as well as they might deterio­rate renal functions. The National Institute for Health and Care Excellence (NICE) did not find evidence that administering NSAIDs could increase the risk of developing COVID-19 or worsened the condition of COVID-19 patients. However, unwanted effects of specific drugs differ substantially in their occurrence and seriousness as well. It seemed to be for a long time that the NSAIDs provoked higher GI-risk was closely related to the COX1/COX2 selectivity, like the cardiovascular (CV) risk to the COX2/COX1 selectivity, however, the recent data did not prove it clearly. Based on the available literature while pondering the gastrointestinal and cardiovascular adverse events, among all NSAIDs the aceclofenac profile seemed to be the most favourable.]

Clinical Oncology

APRIL 30, 2020

[Coronavirus pandemic – new challenges in oncotherapy]

MINÁROVITS János

[This review outlines some of the basic observations related to coronaviruses infecting animals and describes – in a nutshell – the characteristics of human coronaviruses causing mild or severe respiratory diseases in infected individuals. A special attention is given to SARS-CoV-2, the causative agent of the current coronavirus disease (Covid-19) pandemic, and to the pathomechanism of severe acute respiratory syndrome (SARS) which is also accompanied with multiorgan failure in a subset of infected patients. Recently discovered unique molecular features of SARS-CoV-2 are described as well. These molecular cues may affect human to human virus transmission whereas they are absent, remarkably, from the other lung-targeting highly pathogenic human coronaviruses (SARS-CoV-1 and MERS-CoV) which did not spread all over the world. The possibilities of active immunization to prevent SARS-CoV-2 infection and the development of selective small molecule inhibitors curbing the replication of the virus are also touched upon. The review closes with a few remarks regarding the Hungarian and international recommendations concerning the treatment of SARSCoV- 2 infected cancer patients.]

Clinical Oncology

APRIL 30, 2020

[Hormone replacement therapy in cancer survivors – Review of the literature]

DELI Tamás, OROSZ Mónika, JAKAB Attila

[Rapid advance in oncology leads to increasing survival of oncologic patients. More and more of them live long enough to reach either the natural age of menopause or, as a side effect of their oncotherapy, experience the cessation of gonadal function, leading to premature ovarian insuffi ciency, with disturbing vasomotor symtoms and long-term negative cardiovascular and skeletal effects. Thus, an ever increasing number of cancer survivors search endocrinologic help in the form of hormone replacement therapy (HRT). The misinterpretation of the WHI (Women’s Health Initiative) Study has lead to an irrational fear of female hormone replacement, both by the general population and medical professionals. It has seemed the logical and safe conclusion to many physicians to avoid HRT, supposing that this attitude defi nitely causes no harm, whereas the decision of prescribing estrogen alone or with progestins might bear oncologic and thromboembolic risks and may even lead to litigation in case of a potentially related complication. However, it was known even before the WHI results that premature menopause and hypogonadism decreases the life expectancy of women by years through its skeletal and cardiovascular effects, and this negative effect correlates with the length of the hypoestrogenaemic period. Yet, the oncologic risk of HRT is extremely diffi cult to assess. In this work we review the latest evidence from in vitro experiments to clinical studies. We group tumours regarding the oncologic risk of properly chosen female hormone replacement therapy in cancer survivors as follows: ’HRT is advanageous’ (e.g. endometrial cancer type I, cervical adenocarcinoma, haematologic malignancies, local cutaneous malignant melanoma, colorectal cancer, hepatocellular cancer); ’HRT is neutral’ (e.g. BRCA 1/2 mutation carriers without cancer, endometrial cancer type II, uterinal carcinosarcoma and adenosarcoma, certain types of ovarian cancer, cervical, vaginal and vulvar squamous cell carcinoma, prolactinoma, kidney cancer, pancreatic cancer, thyroid cancer); ’HRT is relatively contraindicated’ for various reasons (e.g. leiomyosarcoma, certain types of ovarian tumours, brain tumours, advanced metastatic malignant melanoma, lung cancer, gastric cancer, bladder cancer); ’HRT is diasadvantageous and thus contraindicated’ (e.g. breast cancer, endometrial stroma sarcoma, meningioma, glioma, hormone receptor positive gastric and bladder cancer).]

Lege Artis Medicinae

NOVEMBER 30, 2020

[Some newly discovered mechanisms of action of the immune response and the conceptual transformation of immunology]

FALUS András

[Immunology is a complex science studying healthy and abnormal immune responses. This discipline of physiology and pathophysiology primarily understands the individual mechanisms through a cellular and molecular biological, genetic, epigenetic and (neuro) endocrinological approach, as well as by exploring the details of pathological processes. Im­mu­nology is one of the very rapidly evolving sciences, and its results have repercussions on other disciplines at both theoretical (eg network sciences, systems biology) and methodological (monoclonal antibodies, biomarkers, immune assays) levels. In recent decades, a number of conceptual novelty have been uncovered and immunologists have recognized essential details in their assertion in immunity. ]

Lege Artis Medicinae

NOVEMBER 30, 2020

[Lung cancer – a review of thirty years. Thoughts about the past struggles, the present results and promises of the future]

OSTOROS Gyula

[In the past thirty years there was a huge development in the complex treatment of lung cancer. This development is due mostly to the last decade. Nihilism of lung cancer treatment is over and it is a reality that even patients in advanced stage turn out curable by appropriate therapy and their condition may be changed for a chronic disease while using anti-tumour therapy. Thirty years ago, the realistic life expectancy of six to eight months in advanced stage mounted nowadays significantly, and may surpass even five years in a number of cases. It required adequate diagnostic background, which provided the biomarker based treatment. In early stage surgical resection has a fundamental role, coupled with modern complex neoadjuvant and adjuvant treatment, while new surgical techniques also contributed to the improvement of therapeutic results. The same is true for radiation therapy. The same complex strategy is prevailing also in pharmaceutical options, which are dominated by modalities of cytotoxic chemotherapies and targeted immunothe­rapies. Multidisciplinary teams play a significant role in strategic decisions of lung cancer treatment. The future ways are indicating repeated innovations of tar­geted therapies and extended indica­tions of immunotherapy in terms of precision medicine. However, we must keep in mind also the primary and secondary prevention with effective smoking cessation programs and low-dose chest CT scree­ning applied as usual soon in the risk groups. ]

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 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.]