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Clinical Oncology

MAY 10, 2018

[Immunotherapy of lungcancer – an update]

OSTOROS Gyula

[Ten years ago the median survival of small cell lung cancer (SCLC) and non small cell lung cancer (NSCLC) was less than one year. In the case of SCLC the situation did not change. There are revolutionary new possibilities in the treatment of NSCLC (histology based cytotoxic chemotherapy, molecular targeted therapy etc.). Unfortunately there is no signifi cant development in treatment strategy of SCLC in the last 30 years. Nowadays in NSCLC immune check point inhibitor therapy is a novel treatment method in the clinical praxis as well. The integration of the PD axis and the CTLA4 inhibitors in the complex therapy of the management of NSCLC is a new challenge. The pembrolizumab monotherapy in fi rst line setting is a new standard of care with high PDL1 expression. In second line setting the pembrolizumab, nivolumab and atezolizumab widely used in clinical praxis as well. In locally advanced disease of NSCLC after radiochemotherapy the durvalumab maintenance monotherapy showed a signifi cant progression free survival benefi t, comparing to placebo. We have got new treatment possibilities in the treatment of SCLC as well. The results of clinical trials with antibody conjugate therapy are promising. The nivolumab monotherapy and the combination treatment of nivolumab + ipilimumab gave promising results as well. In the treatment of SCLC and NSCLC there is a need for biomarker selected therapy (tumor mutational burden [TMB], DLL3, cMyc etc.). Based on the new positive results of the clinical trials there is a possibility to transform lung cancer from a subacute disease to a chronic illness.]

Lege Artis Medicinae

MARCH 20, 2019

[How can we reach more effective antihypertensive treatment in diabetic patients with hypertension?]

BENCZÚR Béla, TORZSA Péter

[Hypertension is the leading “silent killer” accounting for 10 million deaths worldwide. It frequently occures together with other metabolic risk factors, including type-2 diabetes mellitus and dyslipidemia augmenting the global cardiovascular risk of patients. Their treatment and reaching target blood pressure means a real challenge for practising physicians. According to the recent hypertension guidelines RAAS-inhibitors are the first choice agents which can be excellently combined with diuretics. RAAS-inhibitor based therapy frequently needs to be completed with Ca-antagonist to which statin should be added in the presence of metabolic risk factors. The benefits of amlodipin/atorvastatin fixed combination are multiple: both agents are capable to inhibit the progression of atherosclerosis and to reach blood pressure and LDL target values. In addition the well-known poor statin-adherence can be improved with fixed combination which can contribute to the reduction of risk of these high-risk subjects. ]

Lege Artis Medicinae

MARCH 20, 2019

[The atherosclerosis can not only be prevented, but also can be cured ]

MÁRK László

[The process of atherosclerosis nowadays plays an important role in the health care not just as a major cause of the most common cardiovascular diseases which lead to death, but also as a major factor in the loss of age-related elasticity in the blood vessels. Over the past two decades, large studies have shown that the treatment of high cholesterol levels can reduce the frequency of cardiovascular events and death and have confirmed the ability to reduce the already existing atherosclerotic plaque, which is almost unique in pharmacotherapy. Using lipid lowering therapy, if we do it properly, we can not only prevent vascular events, but can also cure atherosclerosis. Currently there are three drug groups (statins, ezetimibe and PCSK9- inhibitors), which have complete evidence that their use can reduce the number of cardiovascular events and plaque regression can be achieved. Despite many convincing clinical trials, lipid-lowering therapy is on the cardiovascular prevention palette in the just tolerated or forced applied category. In order to take advantage of its potentials at an appropriate level, as doctors, we have to approach to it by considering its importance. We should communicate to our patients that it’s about a life-long treatment, which not only can reduce the possibility of cardiovascular events, but also can slow down the aging process of the arteries. ]

Lege Artis Medicinae

JANUARY 20, 2019

[Pharmacotherapy of dementia ]

PÁKÁSKI Magdolna, KÁLMÁN János

[The goal of treatment of dementia-related disorders is to reserve cognitive and functional ability, minimize behavioral and psychological disturbances, and slow disease progression, since currently available therapies can not reverse the pathologic processes. Among them, the most common is Alzheimer’s disease and vascular dementia. The authors review the therapeutic guidelines of these dementia types adapted to Hungarian conditions. Cho­li­nesterase inhibitors represent first-line therapy for patients with mild to moderate Alzheimer’s disease, whereas a glutamate N-metil-D-aspartate antagonist is used in the treatment of moderate to severe Alzheimer’s disease. In milder stages, phar­macotherapy may be supplemented by the use of nootropics. The progression slowing drugs have not only impact on cognitive symptoms but also affect behavioral and psychological symptoms. De­pen­ding on the severity of dementia and the existence of behavioral and psychological symptoms, these medicines may be re­commended as monotherapy or in combination. To further alleviate behavioral and psychological symptoms a variety non-pharmacological methods are known, at present their effectiveness has not been proven. Antipsychotics may be used to reduce agitation and aggression. Taking into account the side effects profile of antipsychotics, tiapride or risperidon ad­mi­nistration can be considered. In the case of their ineffectiveness, haloperidol may be used. ]

Hypertension and nephrology

SEPTEMBER 12, 2018

[Treatment of hypertension in kidney transplant patients]

KOVÁCS Tibor, WAGNER László

[Most of the renal transplant recipients suffer from hypertension. Hypertension substantially contributes to the high cardiovascular mortality in this population. The recommendation of the Hungarian Society of Hypertension and the international guidelines suggest to achieve less than 130/80 mmHg as target blood pressure in these patients. Several factors may be in the background of hypertension after kidney transplantation, which can be summarized as factors from the recipient-side, the donorside and factors provoked by transplantation itself. In most of the cases early after transplantation high doses of immunosuppressive drugs (especially calcineurin inhibitors and steroids) are responsible for the increased blood pressure. There are some further special methods apart from the general recommendations which are needed during the examination of hypertension of kidney transplant patients: e.g. measurement of blood trough-level of immunosuppressive drugs, investigation of bone-mineral disorder, screening for the level and causes of anaemia, check-up of the renal graft circulation. Kidney transplant patients suffering from hypertension usually need more than two antihypertensive drugs beyond the use of non-pharmaceutical antihypertensive methods. In the early posttransplantation period calcium channel blockers are preferred antihypertensive medications, because they counterbalance the vasoconstrictive effect of calcineurin inhibitors. The administration of renin-angiotensin-aldosterone inhibitors are rather suggested after the stabilization of renal function (from the 1-3 months posttransplantation). When designing antihypertensive strategy, comorbidities and special factors should be regarded as well, especially volume overload, proteinuria, allograft function (GFR), diabetes, other cardiovascular risk factors, previous cardiovascular events. The setup of an individual therapeutical strategy is advised in view of all these factors, which is different according to the timing after transplantation: the perioperative, the early postoperative phases and from 1-3 months after transplantation have special focuses.]

Lege Artis Medicinae

JUNE 20, 2018

[Treatment of EGFR mutant lung adenocarcinoma after progression]

BOGOS Krisztina

[Precision medicine proposes the personalization of health services in order to make the best individual decisions about the interventions and treatments for the patient. Molecular genetic diagnostic tests help to select the appropriate therapy, so-called targeted therapy. In the case of extensive lung cancer with EGFR mutation, EGFR tyrosine kinase inhibitors are immediately applicable; they are very effective and can reach long-term remission of the disease. However, resistance mutation can develop during the treatment, which causes the progression of the disease; therefore change of therapy is needed. In our case, we show the possibility of targeted treatment beyond the progression, emphasizing the importance of detecting resistance mutation. ]

Hypertension and nephrology

JUNE 10, 2018

[Antihypertensive effect of rilmenidine focusing on the Hungarian multicenter trial VERITAS]

FARSANG Csaba, FINTA Ervin

[Summary in the antihypertensive therapy, in addition to the RAS-blockers (ACE-inhibitors or ARBs), calcium antagonists and thizid-like diuretics, other antihypertensive drugs with different mechanisms of actions, such as the imidazoline I1 receptor agonists, are beneficially used. Several international and Hungarian studies showed the results of the effects of these agents. Authors emphasize the effects of the VERITAS study showing that in hypertensive patients the imidazoline I1 receptor agonist, rilmenidine significantly decreased the office blood pressure as well as the blood pressure measured by ambulatory blood pressure monitoring (ABPM). The white-coat reaction and left ventricular hypertrophy (LVH) were also decreased. In a separate study involving hypertensive subjects rilmenidine significantly increased baroreflex sensitivity. This effect may contribute - mainly during daytime - to the antihypertensive effect. Authors summarise the most important actions of rilmenidine, and the selected publications on the results of the Hungarian and international investigations.]

Clinical Oncology

DECEMBER 05, 2017

[Inhibition of proteasome in cancer therapy]

KOPPER László

[The ubiquitin-proteasome pathway is the most important element in the regulation of intracellular protein metabolism. Its main function is the degradation of the unnecessary proteins either as part of normal metabolic balance or in case of misfolding or part of the deregulation as in cancer cells using proteolytic enzymes. The importance of this pathway has been acknowledge by Nobel prize. In certain diseases as in several malignancies, where the ubiquitin-proteasome pathway is not able to remove the proteins due to dysfunction or accumulation in a high quantity. The unregulated accumulation of proteins could lead to cell death. This phenomenon was proven by the appearance of proteasome-inhibitors targeting mainly myeloma. It should be mentioned that clinical aspects myeloma has been discussed in an excellent review by Mikala and his colleagues in Klinikai Onkológia.]

Clinical Oncology

MAY 10, 2017

[Why don’t immune checkpoint inhibitors work in colorectal cancer?]

SHI Yuequan, ZOU Zifang, KERR David

[In recent years, immune checkpoint inhibitors have been shown to be effective in treating manifold types of cancer but less robust in colorectal cancer (CRC). While, the subgroup of CRC with microsatellite instability (MSI; also termed as mismatch repair defi cient) showed a moderate response to Pembrolizumab in a single arm phase II clinical trial, microsatellite stable (MSS) cancers were unresponsive. Possible mechanisms that affect immune response in colorectal cancer will be reviewed in this article. We will also propose that histone deacetylase (HDAC) inhibition may reverse the immune editing commonly seen in advanced CRC and render them sensitive to immune checkpoint blockade.]

Hypertension and nephrology

OCTOBER 20, 2017

[Therapy of isolated systolic hypertension III.]

FARSANG Csaba

[In the elderly and very elderly (˃80 yrs), a wealth of data from large clinical trials are available, showing the necessity of treatment mostly with drug combinations - fix-combinations are preferred for increasing the adherence/persistence to therapy. Using diuretics, ACE-inhibitors/ARBs with calcium antagonists, and in special cases diuretics and beta blockers are also suggested by recent European guidelines (ESH, HSH). The target is <140 mmHg, but in octogenarians <150 mmHg. Some studies are pressing for even lower SBP (to around 120 mm Hg), but it seems to be wise to balance advantages/disadvantages, so the optimal SBP may be around 130 mmHg.]