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Hypertension and nephrology

FEBRUARY 20, 2018

[Experience with mycophenolate mofetil containing immunosuppressive regimen in de novo kidney transplant recipients (ORANGE study).]

WAGNER László, KALMÁR-NAGY Károly, TORONYI Éva, TÖRÖK Szilárd, PATONAI Attila, SZAKÁLY Péter

[Mycophenolate mofetil (MMF) has been used as an immunosuppressive agent in renal transplant recipients for more than two decades. The aim of the ORANGE study was to collect data with respect to the efficacy and safety of MMF containing immunosuppressive regimens during standard nephrology care in Hungarian clinical centres. Efficacy of the therapy was primarily evaluated via moni - toring of renal function based on glomerular filtration rate (GFR) values calculated on the basis of the MDRD-175 formula. A total number of 128 patients were en rolled in two clinical centres within the frames of an open-label, non-interventional study. During the course of the study, mean GFR values showed stable renal function between the 1st month (53.5±33.4 ml/min/1,73 m2) and the 12th month (58±16.3 ml/min/1,73 m2). Acute graft rejection occurred in 21 patients during the first month, further, 1-1 rejection was documented in the remaining period between 2-6 and 6-12 months after renal transplantation, respectively. The graft survival was 100% 1 month after renal transplantation, while this ratio was calculated to be 98.4% after 12 months.]

Clinical Oncology

SEPTEMBER 10, 2017

[Targeted therapy of the clear cell renal cancer ]

TORDAY László

[The renal cell cancer is among the ten most frequent cancers in developed countries. Its inci dence rate continuously increased until recently. On the other hand, survival parameters of renal cell cancer patients considerably improved in the last decade due to early diagnosis and developments in the treatment of irresectable disease. Huge progress had been made in understanding of the biological background of this chemo- and radiotherapy resistant disease, leading to the introduction of drugs in fi rst and further line treatment acting on VEGF and mTOR signal transduction pathways. Simultaneously, the era of widespread cytokine treatments had been ended. Recent studies had ensured the introduction of several drugs with new mechanism of action (MET, AXL; FGFR, PD-1 inhibition) into the therapy; these new advances completely changed the treatment landscape of RCC further improving progression free and overall survival. In this publication a review of data regarding the targeted treatment of clear cell renal cancer will be provided and as of our recent knowledge therapeutic positions of different drugs used will be discussed.]

Clinical Oncology

SEPTEMBER 10, 2017

[MEK and ERK - against RAS and RAF ]

KOPPER László

[In most cases, the targeted therapy is able to produce clinical response, but after a certain interval it turns to be ineffective due to secondary resistance against the therapy. One of the most demanding challenge in treatment of cancer is to prevent or inhibit such resistance, which could have several forms, e.g. appearance of new driver activating mutations in the treated tumor, clon(s) existed in minority with different mutations (targets) can grow and replace the temporarely sensitive tumor cells (on the basis of tumor heterogeneity); another pathway takes over the role in cancer progression, etc. Such problems are very common in the RAS-RAF-MEK-ERK pathway. These are very important proteins to collect extracellular signals in order to regular different cell functions, especially proliferation. With activating mutations make the RAS-pathway independent from the normal .regulation. To inhibit the consequence of the mutations is largely still an unsolved problem, with few exceptions (e.g. inhibition of BRAF mutations). Theoretically, the inhibition of the next steps of the pathway, MEK and ERK, may stop the pathologically activated signals, partly due to their inhibition, and party to effi ciently decrease the feedback inside the pathway. This review discusses aspects of this possibilities, especially to overcome resistance and prolong the effectiveness of therapy.]

Lege Artis Medicinae

DECEMBER 15, 2017

[Factors influencing anisocytosis among inpatients with chronic kidney disease]

MOLNÁR D. László, KISS István, SZAKONY Szilvia, AMBRUS Csaba

[The coefficient of variation of RDW (RDW-CV) is a predictor of mortality in several patient cohorts. RDW and other factors were analyzed in an earlier report as potential predictors of inpatient mortality. In this paper, determinants of RDW were examined in a sample of hospitalized patients with chronic kidney disease not yet on dialysis using both frequentist and bayesian ANCOVA models. For the non-informative Bayesian model no prior knowledge about the model parameters was assumed. For the informative Bayesian model prior knowledge from previous experience was applied. Calculations were performed in R with the faraway, car and MCMCPack programme packages. Male gender identity, higher mch and mcv were strongly associated with higher RDW. Blood glucose concentration, white blood cell count, blood hemoglobin concentration, platelet count, age and glomerular fil-tration rate showed inverse relationship with RDW levels. ]

Hypertension and nephrology

OCTOBER 20, 2017

[New results on the pathomechanism of antibody-mediated renal allograft rejection]

MEZÔ Blanka, ANDREAS Heilos, RUSAI Krisztina, PROHÁSZKA Zoltán

[Antibody mediated rejection (ABMR) is a severe clinical problem which is the major immunological cause of kidney transplant failure and may develop slowly months or years after transplantation. According to current knowledge, late ABMR is classically caused by the development of donor specific antibodies (DSA) and the complement system is believed to contribute to tissue damage. The detection of ABMR has been facilitated by improved techniques and new test, resulting in changes of the diagnostic criteria from time to time. The clinical interpretation of DSAs is still not clear however the complement binding ability could help to judge their relevance. In this review we discuss the new results on the pathomechanism and current diagnostic guideline of ABMR. Identification and treatment of ABMR before onset of clinical symptoms is still a big challenge but may lead to a significantly better outcome. In our study we are investigating the role of the complement system including quantitative and genetic testing of several complement proteins that can serve as a diagnostic/prognostic marker of the disease.]

Clinical Oncology

FEBRUARY 10, 2017

[Gene modifi ed T cell therapy for patients with cancer]

HECZEY András

[T cells genetically modifi ed to express chimeric antigen receptors can combine the antigen specifi city of monoclonal antibodies with the cytotoxic function, active biodistribution and long term persistence of T cells. The approach can induce 90% complete remission rate in patients with CD19+ lymphoid leukemias; however, the in patients with solid tumors the antitumor effi cacy of CAR T cells have not reached similar levels yet. The increased levels of interleukin-6 due to T cell activation play key roles in the majority of side effects and using anti-IL-6 monoclonal antibody, tocilizumab can effectively treat these complications. Novel gene modifi cation strategies and improvements in CAR T cell manufacturing, the approach has the potential to fundamentally change the way patients with cancer are treated in the not too distant future.]

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.]

Clinical Oncology

FEBRUARY 10, 2017

[Diffuse large B-cell lymphoma – a road to personal therapy]

BÖDÖR Csaba

[The majority of patients with diffuse large B-cell lymphoma can be cured using the standard rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) based therapy. However, approximately 30-40% of the patients are refractory to the therapy or they relapse. The currently available salvage therapies represent a realistic curative approach only for approximately one quarter of the patients. Therefore, there is unmet clinical need for more effi cient fi rst line and salvage therapies in DLBCL. The rapid advances in the fi eld of molecular genetic techniques lead to a better understanding of the biological heterogeneity as well as the discovery of the key factors involved in the pathogenesis of the disease. Nowadays, the distinction between the cases with germinal center B-cell and activated B-cell origin characterized with different prognosis has therapeutic implications. Presently, the therapy of the so-called double-hit lymphomas also represents an unmet clinical need. The next generation sequencing based studies lead to the discovery of novel molecular targets, including components of different cellular signaling pathways, immune checkpoints and components of the microenvironment. Targeted therapies against many of these molecular targets are being tested in different clinical trials. Due the heterogeneity of the disease, it is of critical importance to identify those patient groups who will benefi t from a particular targeted therapy. Hopefully, this risk-adopted therapeutic approach will become soon available for patients with DLBCL. Currently, the R-CHOP therapy still represents the gold standard in treatment of patients with DLBCL.]

Hypertension and nephrology

SEPTEMBER 10, 2017

[Systemic ANCA-associated vasculitis. Induction immunosuppression therapy, complications and outcome. Part 2]

HARIS Ágnes, POLNER Kálmán

[The present review is compiled of two parts, the first part aims to summarize the induction immunosuppressive therapy, the second part delineates the outcome and complications of ANCA-associated vasculitis. ANCA-associated vasculitis is a systemic disease, accompanied with rapidly progressive glomerulonephritis and severe, often life-threatening extrarenal complications. By early diagnosis and immediate initiation of immunosuppressive therapy both patient and renal outcome have been substantially improved. The major aims of modern therapeutic protocols are, besides improving survival, to decrease immunosuppressive drug toxicity and avoid infections. Immunosuppression is based on the combination of large dose of corticosteroid and cyclophosphamide, which is advisable to supplement by plasma exchange. The B-cell depleting anti-CD20 monoclonal antibody rituximab, which has already been available in Hungary, has been proved to be similarly effective in newly diagnosed ANCA-vasculitis, and even more effective in a relapsing disease, compared to cyclophosphamide. Amongst rituximab’s further indications in this disease is the preservation of young women’s fertility, and it also has priority in some other special cases. Early diagnosis and prompt immunosuppressive treatment have resulted that ANCAvasculitis became a treatable disease with reasonably good clinical outcome, yet both the disease and the immunosuppressive medications frequently cause complications, which necessitate continuous alertness of the attending nephrologists.]

Hypertension and nephrology

MAY 20, 2017

[Systemic ANCA-associated vasculitis. Induction immunosuppression therapy, complications and outcome. Part 1]

HARIS Ágnes, POLNER Kálmán

[The present review is compiled of two parts, the first part aims to summarize the induction immunosuppressive therapy, the second part delineates the outcome and complications of ANCA-associated vasculitis. ANCA-associated vasculitis is a systemic disease, accompanied with rapidly progressive glomerulonephritis and severe, often life-threatening extrarenal complications. By early diagnosis and immediate initiation of immunosuppressive therapy, both patient and renal outcome have been substantially improved. The major aims of modern therapeutic protocols are, besides improving survival, to decrease immunosuppressive drug toxicity and avoid infections. Immunosuppression is based on the combination of large dose of corticosteroid and cyclophosphamide, which is advisable to supplement by plasma exchange. The B-cell depleting anti-CD20 monoclonal antibody rituximab, which has already been available in Hungary, has been proved to be similarly effective in newly diagnosed ANCA-vasculitis, and even more effective in a relapsing disease, compared to cyclophosphamide. Amongst rituximab’s further indications in this disease is the preservation of young women’s fertility, and it also has priority in some other special cases. Early diagnosis and prompt immunosuppressive treatment have resulted that ANCAvasculitis became a treatable disease with reasonably good clinical outcome, yet both the disease and the immunosuppressive medications frequently cause complications, which necessitate continuous alertness of the attending nephrologists.]