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Clinical Oncology

DECEMBER 10, 2018

[PI3K–AKT–mTOR pathway as a therapeutic target]


[The PI3K-AKT-mTOR is one of the most busy signalling pathway, accepting and sending the message to the effector compartment. The pathway is very complex with activators (see the name), and inhibitors, as PTEN. Depending of the cell type this pathway participates in almost all functions of a given cell. The members of the pathway may have genetic failures, as a consequence, the risk for the development of different diseases, including cancer is high. Therefore it is logical to produce drugs to inhibit the dysregulated function. Unfortunately, despite the promising preclinical effectivity, so far only 4 drugs can be used to treat cancer patients. There are some hypothesis for the in effectivity, e.g. no useful marker for patient selection, high toxicity, false drivers for targeting. What is sure, combination therapy is much better than monotherapy]

Lege Artis Medicinae

NOVEMBER 15, 2019

[The hypertensive, non-diabetic nephropathy]


[According to the increase of the number of the hypertensive patients the prevalence of hypertensive nephropathy will increase also. According to the data in the Registry of Hungarian Society of Hypertension, in 2015 the proportion of hypertension patients with chronic kidney disease was 12.3% of the males, 39.1% of the females and generally 26.1% of all the hypertensives. In Hungary the hypertensive nephropathy was the 2nd most common condition led to chronic dialysis in 2010 and 2015 (21% and 22%). According to the Hungarian Society of Hypertension 2018 Guideline the classic inhibitors of the renin-angiotensin system can decrease significantly the progression of renal function decline and the proteinuria. ]

Lege Artis Medicinae

NOVEMBER 15, 2019

[Hypertension in the elderly ]

BARNA István

[Elevated isolated systolic pressure is the most common and greatest cardiovascular risk factor with age. The prevalence of hypertension increases with age and ex­ceeds 60% over 70 years. Proper treatment of hypertension in the elderly, even in very old age (> 80 years), increases life expectancy and reduces the risk of cardiovascular events. For patients over 65 years of age, the target blood pressure range is between 130-139 / 70-80 mmHg if the patient tolerates the treatment. In elderly patients with poorer conditions, systolic blood pressure may be <150 mmHg. White-coat hypertension is common, nondipper ratio is increased, autonomic nervous system dysregulation is more common, and orthostatic decrease of blood pressure. The renal function is decreased or already impaired, often resulting in poorer therapeutic cooperation due to impaired cognitive function. The blood pressure lowering effect of targeted lifestyle changes may be the same as medication monotherapy, with the main disadvantage of decreasing adherence over time, for which a proper physician-patient relationship is essential. First-line agents for the treatment of elderly hypertension include angiotensin converting enzyme inhibitors (ACE inhibitors), angiotensin receptor blockers (ARBs), long-acting calcium channel blockers, and thiazide, thiazide-like diuretics. Beta-blockers should be used in the treatment of elderly hypertension if they have other indications (coronary heart disease, heart failure, arrhythmias). More than 70% of hypertensive patients should use combination therapy to achieve target blood pressure. Take advantage of fixed dose combination to improve compliance to optimize treatment. ]

Lege Artis Medicinae

NOVEMBER 15, 2019

[Neuropathic pain: spotligth on amitriptyline]

FEHÉR Gergely, POHL Marietta, KAPUS Krisztián, GOMBOS Katalin, PUSCH Gabriella, MÁK Kornél, KOLTAI Katalin, BANK Gyula, KÓSA Gábor, VARJASI Gábor, TIBOLD Antal

[The management of neuropathic pain is a challenge both for patients and medical professioners. A novel approach is recommended for its management based on the novel neurobiological results of pain research. Multidisciplinary teams and medical consensus are required due to the variety of symptoms and concomittant psychopathology. This approach allows us to avoid extensive diagnostic and trerapeutic workups and appropiate treatment for our patients. Most extensive evidence is available for pharmacological treatment, and currently recommended first-line treatments include antidepressants (tricyclic agents and serotonin-norepinephrine reuptake inhibitors) and anticonvulsants (gabapentin and pregabalin). The aim of our review was to collect articles focusing on the efficacy of the most widely available and cheapest tricyclic agent, amitriptyline in different neuropathic pain conditions. ]

Hypertension and nephrology

OCTOBER 23, 2019

[GLP-1 receptor agonists in the treatment of type 2 diabetes]


[The glucagon-like peptide (GLP)-1 receptor agonists and somewhat later, the sodium-glucose cotransporter (SGLT) -2 inhibitors have brought new perspectives in the antihyperglycemic treatment of type 2 diabetes. The article overviews clinicopharmacologic characteristics of the GLP-1 receptor agonist group, their glycemic and non-glycemic effects, results of the cardiovascular endpoint studies as well as their place in the recent therapeutic guidelines. It is proven, that both glycemic and weight reducing effect is greater of the long-acting (non-prandial) coumpounds as compared to that of the short acting (prandial) derivates, further, that in studies with cardiovascular endpoints they reduced the relative risk of the composite endpoint of non-fatal myocardial infarct, non-fatal stroke and cardiovascular death. Due to the favolurable glycemic and non-glycemic properties their use is advised already in the early course of type 2 diabetes, as combination of the metformin therapy.]

Lege Artis Medicinae

JULY 20, 2019

[How many cardiovascular events can be avoided by a lipid lowering therapy based on preventive guidelines?]

MÁRK László

[The lipid lowering therapy became one of the most important elements in the cardiovascular prevention, yet it is not appropriately evaluated neither by the doctors, nor by the patients. The lipid goal attainment should to be improved according to Hungarian and international data. Using a recommendation guided lipid lowering therapy the most benefit can be expected in the patients at very high risk who alrea­dy had a cardiovascular event, where the LDL-cholesterol goal is 1.8 mmol/L. Calculating upon the data of 170000 patients of Cholesterol Treatment Trialists’ Collaboration a decrease of LDL-cholesterol level from 2.5 mmol/L to 1.8 in 100 patients in 10 years would avoid 3 myocardial infarctions, strokes or death, lowering that from 3.5 mmol/L to the goal would prevent these 3 events within 5 years. Using the traditional LDL-cholesterol lowering medication, high dose statin and ezetimibe, if the attitude of doctors and the compliance of patients would be ideal, the 1.8 mmol/L goal attainment rate would be over 80%. Unfortunately, up to now the reimbursed administration of ezetimibe in Hungary is still bound to a specialist’s recommendation, adding it to any dose of any statin an additional 20% LDL-cholesterol can be expected. The reimbursed administration of PCSK9-inhibitors is possible only based on a special request to National Health Insurance Fund. To achieve a better national cardiovascular morbidity and mortality the attitude of the doctors and the adherence of the patients to the lipid lowering therapy should be improved (it’s the goal of the present paper as well).]

Lege Artis Medicinae

MAY 20, 2019

[Notes on the management of hypertension in chronic kidney disease ]


[The prevalence of hypertension among pa­tients with chronic kidney disease is high, reaching more than 80%. Hypertension is both one of the main causes and also the most common consequence of chronic kidney disease. It is also a main factor responsible for the high cardiovascular morbidity and mortality in this patient population. Blood pressure control can improve patient outcomes, lower cardiovascular risk and slow down the progression of kidney dis­ease, irrespective of the underlying cause. The optimal therapy should therefore focus not only on blood pressure reduction but also on renoprotection. Basic understanding of the renal pathophysiology in hypertension and renal effects of various medications is of paramount importance. In this review, we summarized cornerstones of the antihypertensive therapy in patients with chronic kidney disease. The management of patients receiving kidney replacement therapies, such as hemodialysis, peritoneal dialysis or transplanta­tion requires special knowledge and expe­rience, therefore it is not discussed here. The aim of this review was to allow non-nephrologist physicians to take care of their kidney patients with more confidence and effectiveness.]

Clinical Neuroscience

MAY 30, 2019

[Dopamine agonists in Parkinson’s disease therapy - 15 years of experience of the Neurological Clinics from Tîrgu Mureș. A cross-sectional study ]

SZÁSZ József Attila, CONSTANTIN Viorelia, MIHÁLY István, BIRÓ István, PÉTER Csongor, ORBÁN-KIS Károly, SZATMÁRI Szabolcs

[Background and purpose - There is relatively few data regarding the usage of dopaminagonists for the treatment of Parkinson’s disease; furthermore, there are no publications regarding Central- and Eastern-European countries. The aim of the study was to evaluate the use of dopamine agonists as a therapeutic option amongst Parkinson’s disease patients admitted to the Neurological Clinics of Tîrgu Mures during the last 15 years. Methods - In our study we investigated the data of all Parkinson’s patients treated at our clinics between the 1st of January 2003 and the 31st of December 2017. We analyzed the particularities of dopamine agonists’ usage based on the therapeutic recommendations from the final report of these patients. Regarding time since the diagnosis, we divided the patients in two groups: less than or equal to 5 years and more than 5 years. Results - During the studied period a total of 2379 patients with Parkinson’s disease were treated at the Clinics. From the 1237 patients with disease duration under 5 years 665 received dopamine agonists: 120 as monotherapy, 83 together with monoamine oxidase inhibitors and in 234 cases associated with levodopa. The remaining 228 patients were treated with a triple combination of levodopa, dopamine agonists and monoamine oxidase inhibitors. In patients suffering from Parkinson’s disease for more than 5 years, in 364 cases out of 653 a dopamine agonist was part of the therapy. Conclusion - The usage of dopamine agonists was similar to the data presented in other studies. We consider that clinicians treating the disease should, with the necessary prudence, use the available and recommended dopamine agonist with the utmost courage to their maximum therapeutic potential.]

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]


[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.]

Clinical Oncology

MAY 10, 2018

[Tumor-associated neurological syndromes]

GORKA Eszter, FABÓ Dániel

[Tumor associate neurological symptoms are heterogeneous clinical entities with diverse etiologies, that may infl uence both the central, and peripheral neural system, as a primary or secondary tumor, may due to immune mediated processes. In our review, we summarize the neural syndromes frequently occurring in oncological practice. We focus on the most frequent neuronal tumors, the brain metastases, that are recently affected by the new targeted and immunotherapies showing increasing intracranial activities. We provide details on paraneoplastic neurological syndromes, because, in spite of their relatively rare occurrence, the modern diagnostic protocols may contribute to early diagnosis that are mandatory for detecting the underlying tumor. Finally we describe the neurological side effects of various oncotherapies, such as PD1 inhibitors, that are accompanied by 3% incidence of neurological complications, and chemotherapy related polyneuropathies. We provide support for anticonvulsive drug selection also, based on their drug-interaction profi le.]