Search results

Clinical Neuroscience

JANUARY 30, 2021

Electrophysiological investigation for autonomic dysfunction in patients with myasthenia gravis: A prospective study

NALBANTOGLU Mecbure, AKALIN Ali Mehmet, GUNDUZ Aysegul, KIZILTAN Meral

Myasthenia gravis (MG) is an autoimmune disorder of neuromuscular transmission. Autonomic dysfunction is not a commonly known association with MG. We conducted this study to evaluate autonomic functions in MG & subgroups and to investigate the effects of acetylcholinesterase inhibitors. This study comprised 30 autoimmune MG patients and 30 healthy volunteers. Autonomic tests including sympathetic skin response (SSR) and R-R interval variation analysis (RRIV) was carried out. The tests were performed two times for patients who were under acetylcholinesterase inhibitors during the current assessment. The RRIV rise during hyperventilation was better (p=0.006) and Valsalva ratio (p=0.039) was lower in control group. The SSR amplitudes were lower thereafter drug intake (p=0.030). As much as time went by after drug administration prolonged SSR latencies were obtained (p=0.043).Valsalva ratio was lower in the AchR antibody negative group (p=0.033). The findings showed that both ocular/generalized MG patients have a subclinical parasympathetic abnormality prominent in the AchR antibody negative group and pyridostigmine has a peripheral sympathetic cholinergic noncumulative effect.

Clinical Neuroscience

JANUARY 30, 2021

Matrix metalloproteinases and their tissue inhibitors in relapsing remitting multiple sclerosis: Possible markers and treatment agents

SANLI Arzu, OZTURK Musa, SOYSAL Aysun, DOVENTAS Yasemin, BASOGLU Fulya, GOZUBATIK-CELIK R. Gokcen, BAYBAS Sevim

Matrix metalloproteinases (MMPs), which are synthesized by many cell groups and responsible for the destruction of matrix proteins, and endogen tissue inhibitors of MMPs (TIMPs) have a role in the pathogenesis of Multiple Sclerosis (MS) by affecting the blood-brain barrier. We aimed to investigate the role of MMPs and TIMPs in the immunopathogenesis and in the course of multiple sclerosis (MS). We enrolled 25 relapsing remitting MS patients, who had a definite MS diagnosis according to McDonald criteria and 25 healthy subjects similar for age and gender as control group. MMP-9- and TIMP-1 levels were measured twice in patient group (one time during an attack and one in remission) and once in healthy subjects. MMP-9- and TIMP-levels of patients during attack and remission period and MMP-9/TIMP-1 ratio were found significantly higher than in the control subjects. In patient group MMP-9 and TIMP-1 levels and MMP-9/TIMP-1 ratio during attacks were not significantly different than during remission period. However, when subdivided according to their number of attacks, patients with 2 attacks had significantly higher levels during attack period comparing to remission period (p<0.05); in case of patients with more than 2 attacks did not have a statistically significant difference in attack and remission periods. Matrix metalloproteinases are important actors in MS immunopathogenesis, particularly in the early period and inhibitor agents for these enzymes can be used as a treatment option.

Hypertension and nephrology

DECEMBER 19, 2020

[Possibility of ARNI (angiotensin receptor-neprilysin inhibitor) treatment in hypertension]

KÉKES Ede

[The natriuretic peptide (NP) is an important endocrine, autocrine and paracrine system that is in constant interaction with RAAS and the sympathetic nervous system in order to ensure a continuous cardio-renal homeostasis. In abnormal conditions – if the pressure/volume load develops in the heart or there are some disorder in the vascular tone or in sodium-water balance, the NP system triggers the body’s defense mechanism. The neutral endopeptidase (NEP) inactivates the vasodilator NPs, bradykinin and vasoconstrictor angiotensin II and endothelin I as well. From this knowledge, the idea that inhibition of the effect of NEP (NEPg) offers a potentially beneficial option in the treatment of heart failure and hypertension was initiated, only the stimulatory effect of angiotensin II needs to be blocked. After a lengthy search, they arrived at a dualacting molecule with a beneficial effect of NEP inhibition (secubitrile) and the angiotensin II AT1 receptor antagonist valsartan (ARNI). Several clinical studies have shown that ARNI alone and in combination with other antihypertensive agents significantly reduces SBP and DBP in hypertensive patients. Its effect is also present in isolated systolic hypertension and in chronic kidney disease with high risk. Do not administer with an ACE inhibitor. Based on clinical experience to date, there is a logic expectation that ARNI will also be classified as a useful antihypertensive agent in the near future.]

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

[Immunotherapy of hepatocellular carcinoma]

DEMETER Gyula

[The systemic treatment of HCC was based exclusively on sorafenib near 10 years. In the past 2-3 years some new molecules demostrated their effectivites in phase III clinical trials. So the immuncheckpoint-inhibitors (ICI) demands their place in systemic treatment of HCC. Nivolumab and pembrolizumab are recommended already in second line in NCCN and ESMO clinical guidelines. Nivolumab demostrated his effectivity against the standard treatment sorafenib in a phase III clinical trial, although the results were not signifi cant. However, the combination treatment of atezolizumab and bevacizumab seems better than sorafenib in a phase III clinical trial, so the combination is recommended already in fi rst line in the NCCN guideline. There are more clinical trials with ICIs in progress as in monotherapy as in combination therapy with other modalities.]

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.]

Clinical Oncology

FEBRUARY 28, 2020

[Non-surgical treatment of ovarian cancer]

PIKÓ Béla, LACZÓ Ibolya,, MARIK László

[The primary surgery with an optimal cytoreduction is an essential step during the treatment of the epithelial ovarian cancer because it determines the effectiveness of other therapeutic options as well. Immediately after the surgery a cytostatic infusion typically 40-42.5 degrees Celsius is pumped directly to the abdomen. During the systemic therapy the main point is the 6 months progression free survival because beyond this time the disease could be considered as platinum sensitive, inside this time as platinum refracter or resistant disease. The cytostatic treatment improved during the years from the alkylating agents through the platinum derivates to the administration of paclitaxel with several combinations of them and with more and more signifi cant results and less side effects. The most signifi cant targeted agents are the angiogenesis inhibitors (mainly the bevacizumab) and the PARP-inhibitors which prevents DNA repairs. In order to a PARP-inhibitor could be administered a platinum sensitivity is required while BRCA mutation not. Recently there are promising clinical researches with immunotherapy as well. The main benefi t of the hormonal therapy is the tolerability. Besides the signifi cant improvement in the systemic agents the role of radiotherapy is more and more decreasing, however the treatment of the whole peritoneal surface – mainly with the modern radiation techniques – could be an alternative solution for the chemotherapy. The palliative irradiation which relieve the symptoms could extend the drug-free period and the combination of radiation and chemotherapy could provide further possibilities.]

Clinical Oncology

DECEMBER 30, 2019

[Targeted and immune therapies for hepatocellular carcinoma: Predictions for 2019 and beyond]

MASATOSHI Kudo

[Systemic therapy for hepatocellular carcinoma (HCC) has markedly advanced since the survival benefi t of a molecular targeted agent, sorafenib, were demonstrated in the SHARP and Asia Pacifi c trials in 2007. Treatment options for patients with advanced HCC increased by sorafenib, and long-term survival for patients with advanced stage HCC has become possible to some extent. However, development of a more potent fi rst-line novel molecular targeted agent replacing sorafenib and a potent second-line agent after disease progression on or intolerant to sorafenib has been warranted because sorafenib lacks tumor shrinking/necrotizing effects and induces relatively severe adverse events such as hand foot skin reaction. Many agents in the 1st line and 2nd line setting were attempted to develop between 2007 and 2016, but all of these clinical trials failed. On the other hand, clinical trials of 4 agents (regorafenib, lenvatinib, cabozantinib, and ramucirumab) succeeded in succession in 2017 and 2018, and their use in clinical practice is possible (regorafenib and lenvatinib) or underway (cabozantinib and ramucirumab). Furthermore, all of 5 clinical trials of combination therapy with transcatheter chemoembolization (TACE) plus a molecular targeted agent failed to date, however, the combination of TACE and sorafenib (TACTICS trials) was reported to be successful and presented at ASCO in 2018. Phase 3 clinical trials of immune checkpoint inhibitors and a combination therapy of immune checkpoint inhibitors and molecular targeted agents are also ongoing, which suggests treatment paradigm of HCC in all stages from early, intermediate and advanced stage, is expected to be changed drastically in the very near future.]

Clinical Oncology

AUGUST 30, 2019

[Prevention of drug-related neuropathy in the clinical practice]

VAJDICS Tímea

[There was a revolution of oncological treatments in the last fi ve years caused by introduction of immuncheckpoint inhibitors. Platinum and taxane based chemotherapies are the standard of care of the most frequent malignancies such as colon and breast cancer. Signifi cant improvement was achieved concerning side effects of chemotherapy in the few past decades. Preventive treatment of vomiting, neutropenia, aneamia are now based on clinical evidences. Meanwhile, there remained side effects (including chemotherapy induced neuropathy) which are diffi cult to treat. This article provides overwiev of the pharmacological therapies, vitamins and non-pharmacological procedures aimed to prevent chemotherapy induced neuropathy. Unfortunately still there are no drugs that are highly effective of preventing of chemotherapy induced periferial neuropathy validated in randomized clinical trials.]