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Clinical Neuroscience

JULY 30, 2020

[Recurrent inhibition during Jendrassik maneuver]

LUKÁCS Miklós

[Objective – Conflicting theoretical models exist regarding the mechanism related to the ability of the Jendrassik maneuver to reinforce reflex parameters. Our objective was to investigate if vigorous handgrip would induce changes in recurrent inhibition of soleus motoneurons. Method – Soleus H reflex was evoked by stimulating the tibial nerve at rest and during bilateral vigorous handgrip, alternating single (H1) and paired stimulation (H2). At paired stimulation we used interstimulus intervals of 10, 15, 20 and 25 ms and supramaximal test stimulus. H1- and H2-wave amplitudes were expressed as percentage of maximal M-wave amplitude. Conditioned H2 wave maximal (H2max) and minimal (H2) amplitudes evoked at rest and expressed as a percentage of the unconditioned H1max amplitude were compared with the corresponding values obtained during handgrip by means of paired Student test and Bonferroni correction. Subjects – At the study participated 28 healthy volunteers. Results – The H1max/Mmax × 100 values obtained during handgrip (37.5±10.1) were significantly higher than those obtained at rest (27.1±7.4). The H2max/H1max × 100-va­lues obtained at paired stimulation were significantly higher during handgrip than at rest, while no significant diffe­rence was found between the H2/H1max × 100-values obtained during handgrip and at rest respectively. Discussion – The H2max/H1max is determined by both the excitability of the motoneurons and the recurrent inhibition elicited by the conditioning stimulus, while H2/H1max indicates only the level of recurrent inhibition. According to our results the Renshaw cells retain their inhibitory effect on the soleus alpha motoneurons during remote muscle contraction. Conclusion – Soleus H reflex enhancement during Jendrassik maneuver is not due to decrease of recurrent inhibition. ]

Lege Artis Medicinae

APRIL 18, 2020

[What is worth to know about COVID-19 for (not only) a cardiologist]

HEPP Tamás, CSÉKE Balázs, BENCZÚR Béla

[SARS-CoV-2 virus infection sprang from Wuhan the capital of the Chinese Hubei province, at the end of 2019 and caused a worldwide pandemic with 1.5 million confirmed cases and claimed almost 100 000 victims until the beginning of April, 2020. First analyses of Chinese COVID-patients confirmed that diabetes, hypertension, and cardiovascular diseases were highly prevalent among SARS-CoV2 infected patients, and might be associated with poor outcome. As previously shown for SARS-CoV-1, SARS-CoV-2 similarly utilizes ACE2 as receptor for viral alveolar cell entry. A suspicion has arisen that the widely used ACE-inhibitor/ARB therapy could be potentially harmful for patients suffering from COVID-19 infection as these agents upregulate the ACE2-expressions. From the other point RAAS-blockade might be beneficial due to fact that ACE2 counters the deleterious effects of Angiotensin II. Authors provide a comprehensive over­view of the most recent literature and summarize the link between COVID-19 and car­diovascular disease. It is important to em­phasize that there are no available hu­man evidences confirming if the RAAS-in­hi­bitor therapy were harmful or helpful in pa­tients suffering from COVID-19.]

Clinical Oncology

APRIL 10, 2019

[New perspectives in the treatment of lung cancer]

SZONDY Klára, BOGOS Krisztina

[In recent years, huge research is going on in the fi eld of oncology and as a result, we can see a signifi cantly longer survival in this area of medicine. Lung cancer, which has been taken places in the back for decades, it has not become a curable disease, but begins to belong to the chronic diseases. As a result of brilliant surgical technics and stereotactic radiotherapy, or as a result of changes in drug treatment, 5-year survival is not uncommon in metastatic lung cancer patients, next to relatively long progression free survive. After the third-generation cytotoxic combinations the added growth inhibition (VEGF inhibitor) maintenance therapy or continuous pemetrexed cytotoxic chemotherapy were resulted in high survival benefi ts. The fi rst real breakthrough, long progression-free survival was achieved by targeted treatment, which proved to be effective with known driver mutations. The other great result, especially in squamous cell carcinoma, was the immunotherapy, the inhibition of immune checkpoints, which effi cacy was confi rmed in adenocarcinoma also. Several studies are going on with adjuvant or neoadjuvant immunotherapy, and combined use of immunotherapy (either in combination with radiotherapy or cytotoxic chemotherapy).]

Lege Artis Medicinae

MAY 20, 2019

[Immuno-oncology therapy in patients with non-small cell lung cancer]

CSÁNKY Eszter

[Despite decades of smoking cessation programs, and lung cancer screening programs, mortality due to bronchial cancer leads the mortality statistics among cancer deaths worldwide. Platinum-based chemotherapy has not fundamentally altered the effectiveness of treating non-small cell lung cancer (NSCLC). One of the newest approaches to the use of immunotherapeutic treatments in recent years is the so-called. use of immune checkpoint blocking agents. PD-1 and PD-L1 blockers of this type have been subjected to a large number of clinical trials in lung cancer and were reported by the tumor III.b / IV. stage. Last year, in 2018, we again came up with a milestone in the treatment of lung cancer immuno-oncology, as compared to the previous stage, III.a / III.b Durvalumab con­solidation therapy for non-small cell lung cancer after inoperative, non-chemo-radiotherapy phase I, is based on the results of the PACIFIC clinical trial. PACIFIC was a triple-phase, randomized, double-blind, placebo-controlled, multicentre study to evaluate the efficacy and safety of durvalumab consolidation therapy, irresistible, III. patients with non-small cell lung carcinoma who have not progressed after platinum-based chemo-radiotherapy. The PD-L1 expression level of the tumor was not an admission criterion. In the study, 713 patients were randomized to durvalumab and placebo for 2:1, progression-free survival (PFS) and over­all survival (OS) as their primary endpoint. Summarizing the results of the study, durvalumab provided significant benefit to patients at both endpoints. PFS and OS values were also significantly longer for durvalumab than placebo, and the safety profile of durvalumab was consistent with previous PD-1, PD-L1 inhibition tests.]

Hypertension and nephrology

MAY 10, 2019

[One-year persistence of fixed-dose combinations of angiotensin-converting enzyme inhibitor and calcium channel blocker in hypertensive patients]

SIMONYI Gábor, FERENCI Tamás, FINTA Ervin, IGAZ Iván, BALOGH Sándor, GASPARICS Roland, MEDVEGY Mihály

[Introduction: The most recent European guidelines for the treatment of hypertension suggest the use of renin-angiotensin-aldosterone system antagonists (RAAS inhibitors) and calcium channel blockers (CCBs) or diuretics fixed-dose combinations (FDCs) as the first therapeutic option. In antihypertensive therapy, the patient’s adherence is one of the most important factors in reducing unwanted cardiovascular events. Aim: Our aim was to assess the one-year persistence of angiotensin-converting enzyme inhibitor (ACEI) and CCB FDCs in hypertensive patients. Method: Authors have analysed the prescription database of the National Health Insurance Fund in Hungary on pharmacy claims between October 1, 2012 and September 30, 2013. Those patients were identified who filled prescriptions for FDCs of ACEI and CCBs prescribed for the first time for hypertensive patients and who had not re ceived similar drugs during the year before. Apparatus of survival analysis was used, where ‘survival’ was the time to abandon the medication. Results: 124,388 patients met the inclusion criteria. One-year persistence rate and hazard ratio (HR) of discontinua tion in patients with ramipril/amlodipine FDC was 54% (HR = 1.00, reference), perindopril/amlodipine 47% (HR = 1.30, p<0.0001), lisinopril/amlodipine 36% (HR = 1.79, p<0.0001), ramipril/felodipine 26% (HR = 2.28, p<0.0001) and trandolapril/verapamil 12% (HR = 4.13, p<0.0001). The average survival time of drug limited to 360 days was 270.2 days for ramipril/amlodipine FDC, 242.7 days for perindopril/amlodipine FDC, 211.2 days for lisinopril/amlodipine FDC, 186.3 days for ramipril/felodipine FDC and 125.7 days for trandolapril/verapamil FDC. Conclusions: The authors demonstrated that the one-year persistence of ACEI/CCB FDCs was significantly different in hypertensive patients. Ramipril/amlodipine FDC was more advantageous for patient adherence.]

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. ]

Clinical Oncology

DECEMBER 05, 2017

[Complex therapy of bladder cancer]

LANDHERR László

[Bladder cancer is the most common malignancy involving the urinary system. Urothelial (formerly called transitional cell) carcinoma is the predominant histologic type in the developed countries, where it accounts for approximately 90 percent of all bladder cancers. The optimal management of nonmuscle invasive urothelial cancer is highly important. For patients with muscle invasive cancer the gold standard treatment is the cystectomy. If the patient unable or unwilling to undergo radical cystectomy with urinary diversion, complete TURBT combined with radiation therapy plus chemotherapy may offer an alternative bladder-sparing approach. Patients with muscle invasive disease and regional lymph node metastasis limited to the pelvis (N1-N3), but without more distant lymph node or visceral metastasis may be treated with six cycles of cisplatin-based chemotherapy followed by cystectomy or a combined-modality approach. In metastatic cases the combination chemotherapy may prolong survival and often provides palliation of symptomatic disease. Checkpoint inhibition immunotherapy has substantial clinical activity in post-chemotherapy patients and is the preferred therapy for patients who have progressed after platinumbased therapy or is not suitable for them.]

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

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.]