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Lege Artis Medicinae

JULY 01, 2020

[Sarcopenia – muscle loss – pathomechanism, clinical presentation and metabolic comorbidities]

VERECKEI Edit, HODINKA László

[Sarcopenia, or the age-related involution of muscle strength and muscle mass, is a serious public health concern, due to the growing number of elderly population caused by nowadays demographic changes i.e. prolonged life expectancy. By ageing, the muscle tissue is shrinking gradually, leading to the loss of muscle strength and masses. This condition is called sarcopenia. Sar­co­penia is the simultaneous decrease of muscle mass, muscle strength and functional independence. In parallel the physical performance deteriorates (weakness, slowness and poor physical balancing). Fatigue, el­derly behaviour and weight loss are the consequences of these accumulating deficits, which associate with cognitive decline and result in increasing social isolation. The primary form of sarcopenia is the decrease of the energy production of muscle cells and then the death of muscle cells. Se­con­dary, endocrine dysfunctions, diseases of the nervous system, decreased physical activity, malnutrition or malabsorption, chronic infection accelerate the process and aggravate the patient’s condition. Complex genetic, biochemical and endocrine mechanisms take part in the development of sarcopenia. This involution is due to the impaired balance of restoring and depleting processes of muscles. A questionnaire and algorithm have been developed to recognize, screen and diagnose the risks of sarcopenic condition; these separate the sarcopenic and non-sarcopenic patients with specific cut-off values. Sar­co­penia can be diagnosed based on walking speed, decreased handgrip strength and measured or calculated muscle mass in persons over 65. Sarcopenia can be considered as a phenomenon of “physiological” aging, however, it becomes a disease when diagnostic cut-offs are exceeded and the patient experiences functional disability and declining quality of life. Prevention and treatment of sarcopenia and reducing the risk of falling are based on regular active resistance and coordination exercises. Options for pharmaceutical treatments are limited since despite of identified molecular targets there are no convincingly effective innovative therapy on the horizon. Nevertheless, there are some weak evidence for efficacy of the application of amino acids stimulating muscle cell differentiation, such as leucine or the analogue of beta-hydoxy-methylbutyrate beside exercise therapy.]

Hypertension and nephrology

DECEMBER 12, 2019

[The effect of the β-blockers on left ventricular sytolic and diastolic function]

MOSER György

[The author surveys the pharmacodynamic effects, by which the β- blockers can exercise an influence on systolic and diastolic function. He points out, that the constituents of the effect can be separated only in didactic aspect, its worthwile to take the situation of their interdependence. Analyses the how the when and the wherefore the hemodynamic state determines the component of the complex mode of action that sets off. Deals with the problem, that what kind of effects are desired in certain clinical settings and which of those are deletorious. On emphasized he discusses the greatest danger of the β-blockade, the negative inotropic effect, and the mode of its offset or rather counteraction of its hemodinamic result.]

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. ]

Hypertension and nephrology

OCTOBER 23, 2019

[Blood pressure management for stroke prevention and in the acute stroke. The new guideline of European Society of Hypertension (ESH, 2018), European Society of Cardiology and Hungarian Society of Hypertension (HSH, 2018)]

JENEI Zoltán

[Hypertension is the leading modifiable risk factor for stroke. Its prevalence amongst stroke patient is about 60-70% and the benefit of blood pressure (BP) lowering therapy on stroke risk reduction is well established. However the optimal BP targets for preventing stroke and reducing stroke consequences have been controversial. The new European (ESC/ESH) and Hungarian (HSH) hypertension guideline published in 2018 highlighted the primary and secondary prevention of stroke and the BP management in the acute stroke care as well. According results from ACCORD, SPRINT, HOPE-3, and other metaanalysis the systolic blood pressure (SBP) lowering < 120 mmHg has not favourable effect, thus in hypertensive patients < 65 years the SBP should be lowered to a BP range of 120-129 mmHg. In older patients ≥ 65 years the SBP should be targeted to a BP range of 130-139 mmHg (IA). In patients with acute intracerebral haemorrhage careful acute BP lowering with iv. therapy, to <180 mmHg should be considered only in case of SBP ≥ 220 mmHg (IIaB). In patients with acute ischaemic stroke who are eligible for iv. thrombolysis, BP should be carefully lowered and maintained to < 180/105 mmHg for at least the first 24 h after thrombolysis (IIaB). If the patient is not eli gible for lysis and BP ≤ 220/110 mmHg, routine BP lowering drug therapy is not recommended inside 48-72 h (IA). In patients with markedly elevated BP > 220/110 mmHg who do not receive fibrinolysis, drug therapy may be considered, based on clinical judgement, to reduce BP by 15% during the first 24 h after the stroke onset (IIbC). After 72 h of acute stroke in case of hypertensive patients < 65 years the SBP should be lowered to a BP range of 120-129 mmHg (IIaB). In older patients ≥ 65 years the SBP should be targeted to a BP range of 130-139 mmHg (IA). If BP < 140/90 mmHg after stroke, the BP lowering should be considered (IIbA). It is recommended to initiate an antihypertensive treatment with combination, preferably single pill combination of renin-angiotensin system blockers plus a calcium channel blocker and/or a thiazide like diuretics (IA). Lowering SBP < 120 mmHg is not recommended due to advers events regardless of age and type of stroke either in primary or secondary stroke prevention.]

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

[Circulatory dinamics assay about lercanidipine treatment]

MOSER György

[Lercanidipine is of unique importance amongst calcium channel blockers. In the first section, the author creates two visual analogies to demonstrate the effect of calcium channel blockers. The control of the parallelism of the particular elements of the model of circulatory dynamics, and the biostructure was supported by an engineer of flud dynamics. In the second part, he deals with the effect of these drugs exerted on the pulmonary circulation and renal function, primarily for mind-raising purposes. He focuses on the edema induced by dihydropyridines, pays attention to its patomechanism, prevention and therapy, highlighting the distinctive benefits of lercanidipine. The presence or disappearance of this adverse effect may arbitrate whether this effective and valuable pharmacological intervention should stand the test of clinical practice.]

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.]

Hypertension and nephrology

FEBRUARY 20, 2019

[Carvedilol in chronic kidney disease]

CSIKY Botond

[Chronic kidney disease (CKD) is endemic affecting 850 million people worldwide. Adequate antihypertensive treatment slows the progression of the kidney disease and also decreases the mortality of this population. Because of the comorbidities and the high cardiovascular risk beta-blockers have to be administered frequently in these patients. Carvedilol is a 3rd generation non-selective beta-blocker with alpha- 1 receptor blocking and antioxidant properties. It is metabolically neutral, it does not increase the risk of new onset diabetes and it does not increase the patients’ body weight. In some animal models of CKD and in several human CKD studies carvedilol has shown to have nephroprotective properties and it also decreased the cardiovascular risk in combination therapies.]

Hypertension and nephrology

SEPTEMBER 12, 2018

[Treatment of hypertension in kidney transplant patients]

KOVÁCS Tibor, WAGNER László

[Most of the renal transplant recipients suffer from hypertension. Hypertension substantially contributes to the high cardiovascular mortality in this population. The recommendation of the Hungarian Society of Hypertension and the international guidelines suggest to achieve less than 130/80 mmHg as target blood pressure in these patients. Several factors may be in the background of hypertension after kidney transplantation, which can be summarized as factors from the recipient-side, the donorside and factors provoked by transplantation itself. In most of the cases early after transplantation high doses of immunosuppressive drugs (especially calcineurin inhibitors and steroids) are responsible for the increased blood pressure. There are some further special methods apart from the general recommendations which are needed during the examination of hypertension of kidney transplant patients: e.g. measurement of blood trough-level of immunosuppressive drugs, investigation of bone-mineral disorder, screening for the level and causes of anaemia, check-up of the renal graft circulation. Kidney transplant patients suffering from hypertension usually need more than two antihypertensive drugs beyond the use of non-pharmaceutical antihypertensive methods. In the early posttransplantation period calcium channel blockers are preferred antihypertensive medications, because they counterbalance the vasoconstrictive effect of calcineurin inhibitors. The administration of renin-angiotensin-aldosterone inhibitors are rather suggested after the stabilization of renal function (from the 1-3 months posttransplantation). When designing antihypertensive strategy, comorbidities and special factors should be regarded as well, especially volume overload, proteinuria, allograft function (GFR), diabetes, other cardiovascular risk factors, previous cardiovascular events. The setup of an individual therapeutical strategy is advised in view of all these factors, which is different according to the timing after transplantation: the perioperative, the early postoperative phases and from 1-3 months after transplantation have special focuses.]

Hypertension and nephrology

JUNE 10, 2018

[Antihypertensive effect of rilmenidine focusing on the Hungarian multicenter trial VERITAS]

FARSANG Csaba, FINTA Ervin

[Summary in the antihypertensive therapy, in addition to the RAS-blockers (ACE-inhibitors or ARBs), calcium antagonists and thizid-like diuretics, other antihypertensive drugs with different mechanisms of actions, such as the imidazoline I1 receptor agonists, are beneficially used. Several international and Hungarian studies showed the results of the effects of these agents. Authors emphasize the effects of the VERITAS study showing that in hypertensive patients the imidazoline I1 receptor agonist, rilmenidine significantly decreased the office blood pressure as well as the blood pressure measured by ambulatory blood pressure monitoring (ABPM). The white-coat reaction and left ventricular hypertrophy (LVH) were also decreased. In a separate study involving hypertensive subjects rilmenidine significantly increased baroreflex sensitivity. This effect may contribute - mainly during daytime - to the antihypertensive effect. Authors summarise the most important actions of rilmenidine, and the selected publications on the results of the Hungarian and international investigations.]