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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.]

Hypertension and nephrology

DECEMBER 19, 2020

[The efficiency of angiotensin receptor blocker/neprilysin inhibitor (ARNi) treatment in heart failure 2020 ARNI, VIDI, VICI…]

VÁRALLYAY Zoltán

[A new compound ARNi (valsartan/sacubitril) – as a member of a new pharmacoterapeutic group – has several clinical evidences almost in the whole spectrum of heart failure, especially in case of reduced left ventricular ejection fraction and hypertension. The most important and essential evidence based studies and the efficiency of the treatment with ARNi in heart failure have been demonstrated in this overview. Due to the favorable results of the studies the recommendations of ARNi indication are increasingly dominant in the clinical guidelines. The usage provides effective, safe therapeutic help for the poor life expectancy heart failure patients in the everyday clinical practice. The treatment is already available in Hungary.]

Clinical Oncology

APRIL 30, 2020

[Hormone replacement therapy in cancer survivors – Review of the literature]

DELI Tamás, OROSZ Mónika, JAKAB Attila

[Rapid advance in oncology leads to increasing survival of oncologic patients. More and more of them live long enough to reach either the natural age of menopause or, as a side effect of their oncotherapy, experience the cessation of gonadal function, leading to premature ovarian insuffi ciency, with disturbing vasomotor symtoms and long-term negative cardiovascular and skeletal effects. Thus, an ever increasing number of cancer survivors search endocrinologic help in the form of hormone replacement therapy (HRT). The misinterpretation of the WHI (Women’s Health Initiative) Study has lead to an irrational fear of female hormone replacement, both by the general population and medical professionals. It has seemed the logical and safe conclusion to many physicians to avoid HRT, supposing that this attitude defi nitely causes no harm, whereas the decision of prescribing estrogen alone or with progestins might bear oncologic and thromboembolic risks and may even lead to litigation in case of a potentially related complication. However, it was known even before the WHI results that premature menopause and hypogonadism decreases the life expectancy of women by years through its skeletal and cardiovascular effects, and this negative effect correlates with the length of the hypoestrogenaemic period. Yet, the oncologic risk of HRT is extremely diffi cult to assess. In this work we review the latest evidence from in vitro experiments to clinical studies. We group tumours regarding the oncologic risk of properly chosen female hormone replacement therapy in cancer survivors as follows: ’HRT is advanageous’ (e.g. endometrial cancer type I, cervical adenocarcinoma, haematologic malignancies, local cutaneous malignant melanoma, colorectal cancer, hepatocellular cancer); ’HRT is neutral’ (e.g. BRCA 1/2 mutation carriers without cancer, endometrial cancer type II, uterinal carcinosarcoma and adenosarcoma, certain types of ovarian cancer, cervical, vaginal and vulvar squamous cell carcinoma, prolactinoma, kidney cancer, pancreatic cancer, thyroid cancer); ’HRT is relatively contraindicated’ for various reasons (e.g. leiomyosarcoma, certain types of ovarian tumours, brain tumours, advanced metastatic malignant melanoma, lung cancer, gastric cancer, bladder cancer); ’HRT is diasadvantageous and thus contraindicated’ (e.g. breast cancer, endometrial stroma sarcoma, meningioma, glioma, hormone receptor positive gastric and bladder cancer).]

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

AUGUST 30, 2019

[Role of calcium metabolism in malignant diseases]

MÉSZÁROS Szilvia, TAKÁCS István

[Calcium plays a key role in a wide range of biologic functions. It is involved in skeletal mineralization, muscle functions, nerve transmission, and hormonal secretion and modulate various cellular functions too. Lines of research, on possible association of calcium metabolism regulation with tumorigenesis have been extensively studied in the recent decades. Implying disruptions and/or alterations of known regulatory and molecular pathways can lead to severe, sometimes life-threatening complications. The shift in physiological regulation and pathological factors also affect bone metastases and hypercalcaemia in cancer patients. For this reason, it is important to know about the changes in calcium metabolism and its treatment options in cancerous diseases.]

Lege Artis Medicinae

NOVEMBER 30, 2020

[GLP-1 receptor agonists in the elderly]

WINKLER Gábor

[According to current guidelines of type 2 diabetes, treatment, glucagon-like pep­tide (GLP) -1 receptor agonists (RAs) are primary suggested drugs of the early antidiabetic medication, just after the first an­ti­­diabetic metformin. However, more and more arguments support their optional application in old age diabetes. These include multi-target strong glycemic ef­fects, low risk of hypoglycaemia, proven cardio- and nephroprotective nature of long- and ultra long-acting derivatives, multifaceted be­neficial pleiotropic effects, as well as the appearence of their fixed combinations with analogue basal insulins effective in weight loss and lowering the blood pressure. This study reviews specific aspects of blood sugar lowering treatment in the elderly and the potential benefits of choosing GLP-1 RAs in this age group. While presenting data of relevant literature and own experiences it is emphasized, that these preparations can be used safely in long term also in this age group.]

Clinical Neuroscience

SEPTEMBER 30, 2020

TLR4 (Toll-like receptor-4) expression and frontal-cingulate volumes in schizophrenia

LI Hua, KÉRI Szabolcs

Evidence suggests that pathogen-associated pattern recognition receptors (Toll-like receptors, TLRs) are implicated in the pathophysiology of schizophrenia. TLRs are important in both peripheral immune responses and neuronal plasticity. However, the relationship between peripheral TLR expression and regional brain volumes is unknown in schizophrenia. We therefore assessed 30 drug-naïve, first-episode patients with schizophrenia. TLR4+/TLR1+ monocytes were measured using flow-cytometry. High resolution magnetic resonance images (T1 MRI) were obtained and analyzed with FreeSurfer. Results revealed significant negative correlations between the percentage of TLR4+ monocytes, mean fluorescent intensities, and brain volumes in frontal and anterior cingulate regions. The measures of TLR1+ monocytes did not show significant relationships with regional brain volumes. These results raise the possibility that abnormal TLR-activation is associated with decreased brain volumes in schizophrenia.

Lege Artis Medicinae

JULY 01, 2020

[Persisting Hashimoto’s thyroiditis converting to Graves’ disease]

TÓTH Géza

[Graves’disease and Hashimoto’s thyroiditis are the two most important types of autoimmune thyroid dis­eases. Autoimmune hyperthyroidism commonly leads later on to hypothyroidism. The conversion from persisting Hashimoto-thyroiditis to hyperthyroidism is rare in the literature. The author presents the cases of two patients, whose Hashimoto’s thyroiditis treated with thyroxin for years, changed into Graves’ hyperthyroidism sponta­neously. CASE REPORT – The patients had been diagnosed with autoimmune hypothyroidism since several years. The clinical symp­­toms, the low peripheral hormone le­vels, the high level of antithyroid antibo­dies and the ultrasound imaging confirmed the hypertrophic form of Hashimoto’s thy­roiditis. After several years of high dose le­vothyroxin treatment, clinical symptoms of hyperthyroidism have appeared. After omit­ting the substitution, the thyroid hormone levelled off at high values and the level of anti-TSH receptor antibodies raised too. The diffuse, obviously increased blood flow of the thyroid glands, and in one of the patients the thyroid scan, confirmed the Graves’ disease. During the thyreostatic treatment, the symptoms of the patients disappeared, they became euthyreoid and the antibody levels decreased as well. The Graves’ disease and the Hashimoto’s thyroiditis have many common features. These immunological, ge­netic and other common features enable the mutual transition of these two diseases.]

Hypertension and nephrology

JUNE 24, 2020

[Covid-19 and the kidney]

PATÓ Éva, DEÁK György

[Covid-19 pandemy has emerged from Wuhan, China in December 2019. The infection affects not only the lung but other organs such as the kidney, as well. The relation between Covid-19 infection and the kidney is bidirectional. On one hand, Covid-19 infection may cause kidney damage in 50-75% of the cases resulting in proteinuria, haematuria and acute kidney injury (AKI). The etiology of AKI is multifactorial. Main pathogenic mechanisms are direct proximal tubular cell damage, sepsis-related haemodinamic derangement, citokine storm and hypercoagulability. The virus enters proximal tubular cells and podocytes via the ACE2 receptor followed by multiplication in the lysomes and consequential cell lesion. Histopathology shows acute tubular necrosis and acute tubulointerstitial nephritis. AKI is a strong predictor of mortality in critically ill patients. On the other hand, the risk of Covid-19 infection and mortality is substantially increased in patients with chronic kidney disease – especially in those with a kidney transplant or on dialysis – due to their immunocompromised status. Among haemodialysis patients, infection may spread very easily due to the possibility of getting contacted in the ambulance car or at the dialysis unit. The mortality rate of patients on renal replacement therapy with Covid-19 infection is 20-35%. In order to avoid mass infection it is obligatory to employ preventive measures and implement restricions along with (cohors) isolation of infected patients. In Hungary, every dialysis or kidney transplant patient with Covid-19 infection should be admitted to dedicated Covid-19 wards.]

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.]