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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.]

Clinical Oncology

FEBRUARY 10, 2017

[Cell cycle as therapeutic target – CDK4/6 inhibition]

KOPPER László

[One of the most important decision of a cell: to live or die. If survival is the choice, there are three options: proliferate, to stay in sleeping state for a while, or differentiate in order to perform its specifi c function. These decisions are under a very strict molecular regulation infl uenced by internal and external factors. Tumor cells more and more disregard the regulations, and move into independency for a continuous proliferation, which has a very similar program in normal and tumor cells. The main route towards mitosis is the cell cycle, under the supervision of positive and negative regulators, forming checkpoints, telling to the cell - under the infl uence of mitogenic signals - to go or to stop. The most critical checkpoint is at the border of G1 and S phases where the main players are cyclinD, CDK4/6 and RB1. It turned out that the best targets to inhibit cell proliferation are the CDKs, but this approach, when used unselected targets, was unsuccessful due to the toxicity. To improve the clinical results, the selection of CDK4/6 as a therapeutic target seems to fulfi l most of the hopes. Today three drugs are the most promising: palbociclib (with an acceptance by FDA and EMA to treat breast cancer patients), abemaciclib and ribociclib (underclinical trials). Now, most of the data concern breast cancer, especially the combinations of CDK4/6 inhibitors and endocrine therapy, but many other malignancies are studied (e.g. liposarcoma, mantel cell lymphoma, melanoma, renal cancer, lung cancer, pancreatic cancer, ovarian cancer, teratomas etc.). The key points are the side-effects, the most frequently observed is neutropenia, but so far it is managed without serious toxicity.]

Lege Artis Medicinae

JULY 20, 2017

[We are witnessing a paradigm shift in the management of type 2 diabetes mellitus. Where to place the SGLT2 inhibitors?]

KIS János Tibor

[We are witnessing a paradigm shift in the management of type 2 diabetes mellitus. Instead of correcting carbohydrate parameters only, we need to concentrate on preventing cardiovascular complications as well. The onset of non-insulin formulations is also a shift from previous practice. The author examines the position of SGLT2 inhibitors in the changed therapeutic practice. ]

Hypertension and nephrology

MAY 20, 2017

[Isolated systolic hypertension in children and young adults I.]

FARSANG Csaba

[Prevalence of the isolated increase in systolic blood pressure ≥140 mmHg with normal or low diastolic blood pressure ≤80 mmHg, is defined as isolated systolic hypertension. Its prevalence increases with age up to >90% in patients aged >90 years. Isolated systolic hypertension is also found in the young and the clinical significance of it is still debated. For the therapy, those drugs should be used which have a license for use in children: angiotensin converting enzyme inhibitors, angiotensin AT-1 receptor antagonists, calcium channel blockers beta-blockers and diuretics and their combinations. The young adults with isolated systolic hypertension had a much higher risk of dying from coronary heart disease or cardiovascular disease, then the normotensive individuals, and should be treated to normalise their blood pressure. 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 when needed diuretics and beta-blockers are suggested by recent European guidelines. 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.]

Clinical Oncology

SEPTEMBER 15, 2016

[Novelties in the management of Hodgkin lymphoma]

ILLÉS Árpád, MOLNÁR Zsuzsa, MILTÉNYI Zsófia

[Hodgkin lymphoma is a lymphoproliferativ disease, it is about 12-18% of all lymphomas. It has typical morphologic, clinical and therapeutic features, which can distinguish from other lymphoma types. Due to risk- and PET/CT adapted treatment Hodgkin lymphoma is a curable lymphoma with an 80-90% long-term survival, however, refracter- and relapsed patients’ therapy is a great challange. Cure rate can increase due to the development of the diagnostic and treatment modalities, but the use of standard recommendation is necessary. The aim of this review is to show new WHO 2016 lymphoma classifi cation, role of the new diagnostic options, especially 18FDG-PET/CT, Lugano classifi cation and fi rst-line and salvage therapeutic possibilities and to introduce the immunotherapy, like brentuximab vedotin and PD1 inhibitors. Certain points of hemopoietic stem cell transplantation will be also covered.]

Clinical Oncology

DECEMBER 10, 2016

[Defi ciency of DNA-repair]

KOPPER László

[The cell uses the DNA to keep those information, which are vital to function properly. It is essential to maintain the integrity of the DNA, the stability of the genome. Since DNA damages, caused by external or internal factors, are continuously produced, DNA-repair mechanisms should be ready to identify and eliminate the damages. Either the repair system is successful and the cell can continue its duty, or, if the damages are unrepaired, the programed cell death (apoptosis) is activated according to the rule, that it is prohibited to transfer genomic/epigenomic damages into the daughter cells. It is true that the severness of the damages are not the same. The most important is the identifi cation and repair of those damages which can make genomic instability increasing the risk of cancer development. This may happen when the repair system is insuffi cient, sometimes due to inherited mutations (e.g. BRCA1 mutations can increase the risk of breast cancer, ovarian cancer etc.). Among the damages the DNA double strand breaks are rather common, and also, that the breaks are intended to be repaired in most cases. However, if such repair fails, the cell, here the cancer cell, due to the overhelming damages will dye. This phenomenon is the synthetic lethality. An example: „cooperation” of inherited BRCA1 mutation and PARP-inhibition, can lead to clinical response using PARP inhibitors, as oliparib. New agents and clinical trials intend to take advantage from synthetic lethality.]

Clinical Oncology

FEBRUARY 15, 2016

[Follicular lymphoma - a way to personalized and targeted therapy ]

BÖDÖR Csaba, SCHNEIDER Tamás

[Although follicular lymphoma is the most frequent non-Hodgkin’s lymphoma with an indolent clinical course, it is a rare disease. Patients with FL are characterized with a long survival with a relatively good quality of life, however using the current standard chemo-immunotherapy, the disease is considered incurable. The increasing knowledge of the molecular genetic background of the disease and the role of the reactive microenvironment lead to a better understanding of the pathogenesis of follicular lymphoma. Furthermore, the detailed functional characterization of the various cell surface antigens and deciphering the complex network of signaling pathways catalyzed the development of a number of novel targeted therapies (monoclonal antibodies, kinase- and NFκB-inhibitors), while understanding the effects of the cell surface receptors of cytotoxic T-cells initiated development of the monoclonal checkpoint inhibitors. The epigenetic therapies represent a novel therapeutic area with methyltransferase inhibitors demonstrating the most favorable results. Among the novel therapies, the immunomodulatory lenalidomide appears as the most promising and most effective drug, which acts via regulating the microenvironment, and in combination with rituximab in fi rst line setting it demonstrated similar effi cacy to the current standard protocols. Indeed, the rational use of the novel data and drugs paves the way towards personalized and targeted therapies for FL, resulting in more effective treatment and further improvement in patients’ survival, with a very long disease-free survival representing cure.]

Hypertension and nephrology

APRIL 10, 2017

[Angiotensin-converting enyzme inhibitors before and after myocardial infarction]

TOMCSÁNYI János

[In this review current knowledge related to the coronary atherosclerosis and angiotensin-enzym inhibitor is discussed. The earlier recognition to the effect of ACE inhibitors and ARBs to slow or reverse left ventricular remodelling is well known and accepted but the effect of these drugs on the atherosclerotic process itself may be aqual important. The focus should be now how to treat the early phase of coronary atherosclerosis, how to treat safety the hypertensive patient in the setting of coronary stenosis, how to treat the acute myocardial infarction’s patient with renal failure, and at least how to improve the long-time adherence in the primer and secunder prevention too.]

Hypertension and nephrology

DECEMBER 20, 2016

[New development in the pathogenesis, diagnosis and treatment of IgA nephropathy]

NAGY Judit, VAS Tibor, KOVÁCS Tibor

[IgA nephropathy is one of the leading cause of primary glomerulonephritis worldwide. IgA nephropathy is regarded as an immune mediated disease with a multi-hit pathogenesis starting with the production of poorly glycosylated IgA1 and glycan-specific IgG and IgA autoantibodies leading to the formation of IgA1 containing immune complexes. These immune complexes deposit in the glomerular mesangium followed by the onset of mesangioproliferative glomerulonephritis. The disease has variable clinical presentation and outcome. There is a need to identify patients who have the potential to progress to end-stage renal disease with the help of clinical, histological and biological markers. Treatment options for IgA nephropathy are largely based on opinion or weak evidence. It is true for the KDIGO Clinical Practice Guideline for Glomerulonephritis treatment recommendations containing low level of evidence for almost all recommendations related to IgA nephropathy. It is suggested to separate the patients into 3 groups on the basis of risk to progression and to give not-specific supportive treatment (especially angiotensin converting enzyme inhibitors or angiotensin receptor blocking agents) to all of them on the basis of the risk factors. We discuss the recommendations of the KDIGO Guideline about steroid and immunosuppressive treatment for moderate and high risk patients. Lastly, we provide our perspective on the existing other treatment options (tonsillectomy etc.) and on ongoing clinical trials.]

Hypertension and nephrology

DECEMBER 20, 2016

[Hypertension and atrial fibrillation]

SZŐKE Vince Bertalan, BARACSI-BOTOS Viktória, JÁRAI Zoltán

[Hypertension is the most important independent risk factor of atrial fibrillation, the most common clinically significant arrhythmia. Increased atrial wall tension, myocardium remodelling, activation of renin-angiotensin-aldosterone system (RAAS) and fibrotic remodelling are possible hypertension induced mechanisms which can contribute to developing atrial fibrillation. Knowing the relation of hypertension to atrial fibrillation is crucial in the need for effective and up-to-date therapeutic strategies. RAAS inhibitors and beta blockers prevent atrial fibrillation not only by lowering blood pressure but partly due to the inhibition of the above mentioned mechanisms. Complications of hypertension, such as left ventricular hypertrophy and hypertensive cardiomyopathy are substantially limiting the number of drugs that can be used for rhythm control. In most cases in the presence of hypertension initiation of anticoagulation therapy is necessary too.]