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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.]

Clinical Neuroscience

JULY 30, 2020

[Decisional collisions between evidence and experience based medicine in care of people with epilepsy]

RAJNA Péter

[Background – Based on the literature and his long-term clinical practice the author stresses the main collisions of evidence and experience based medicine in the care of people with epilepsy. Purpose – To see, what are the professional decisions of high responsibility in the epilepsy-care, in whose the relevant clinical research is still lacking or does not give a satisfactory basis. Methods – Following the structure of the Hungarian Guideline the author points the critical situations and decisions. He explains also the causes of the dilemmas: the lack or uncertainty of evidences or the difficulty of scientific investigation of the situation. Results – There are some priorities of experience based medicine in the following areas: definition of epilepsy, classification of seizures, etiology – including genetic background –, role of precipitating and provoking factors. These are able to influence the complex diagnosis. In the pharmacotherapy the choice of the first drug and the optimal algorithm as well as the tasks during the care are also depends on personal experiences sometimes contradictory to the official recommendations. Same can occur in the choice of the non-pharmacological treatments and rehabilitation. Discussion and conclusion – Personal professional experiences (and interests of patients) must be obligatory accessories of evidence based attitude, but for achieving the optimal results, in some situations they replace the official recommendations. Therefore it is very important that the problematic patients do meet experts having necessary experiences and also professional responsibility to help in these decisions. ]

Lege Artis Medicinae

APRIL 18, 2020

[Interrelations between antidepressants and diabetes]

HARGITTAY Csenge, GONDA Xénia, MÁRKUS Bernadett, VÖRÖS Krisztián, TABÁK Gy. Ádám, KALABAY László, RIHMER Zoltán, TORZSA Péter

[Diabetes and depression are frequent comorbidities. They are a heavy burden by themselves, however, as comorbidities increase additionally the number of diabetes-related complications, morbidity, and mortality. In the background of interrelations, there are both well-known and hypothetical mechanisms. The aim of the present review is to outline these interrelations between antidepressants and diabetes and to discuss the effect of medications on carbohydrate metabolism respectively. Anti­depressant treatment on the one hand may improve mood, cognitive function and medication adherence leading to an improved glucose metabolism, on the other hand through their metabolic side effects, they may worsen carbohydrate metabolism. Concerning metabolic side effects, selec­tive serotonin reuptake inhibitors are the sa­fest, while tricyclic antidepressants and mo­noamine oxidase inhibitors should be administered under close monitoring. Se­rotonin and noradrenaline reuptake inhibitors may deteriorate gly­cae­mic control via increased noradre­nergic activation. Novel antidepressants, how­ever, have a neutral or positive impact on gly­caemic measures. Screening for and temporally adjusted treatment of depres­sion may decrease the risk of comorbidities ge­nerated complications. While caring for diabetic patients with depression, one should consider metabolic side effects of antidepressants and close monitoring of carbohydrate metabolism.]

Clinical Neuroscience

JANUARY 30, 2016

To treat or not to treat, cheyne-stokes respiration in a young adult with vascular encephalopathy

HUBATSCH Mihaela, ENGLERT Harald, WAGNER Ulrich

Cheyne-Stokes respiration (CSR) is a form of sleep-disordered breathing characterised by recurrent central sleep apnoea alternating with a crescendo-decrescendo pattern of tidal volume, relatively rare observation in sleep labs. It is mainly seen in severe heart failure and stroke. We report the case of a young man with CSR after sudden onset of seizure in the context of hypertensive exacerbation leading to the diagnosis of a leukoencephalopathy, and comment on differential diagnoses, prognostic and therapeutic outcomes. The very uniqueness of this case consists in the extremely young age for developing a vascular encephalopathy in the absence of genetic diseases and without previous diagnose of hypertension. There is no adequate explanation for the origin of vascular encephalopathy; also there is lack of evidence regarding the benefits and modality of treatment for CSR in neurologic diseases. Thus, we were forced to find the best compromise in a nocturnal oxygen therapy and follow-up.

Hypertension and nephrology

APRIL 24, 2020

[Cardiovascular risk assessment in chronic kidney disease, significance of left ventricular myocardial mass index]

SÁGI Balázs, KÉSŐI István, VAS Tibor, CSIKY Botond, NAGY Judit, KOVÁCS Tibor

[Introduction: Earlier studies have shown that cardiovascular (CV) mortality and morbidity in chronic kidney disease (CKD) often exceed their average population, and left ventricular hypertrophy (LVH) is an independent risk factor for CV disease. However, in CKD, the relationship between LVH, arterial stiffness (AS) and renal function has not yet been fully elucidated. Little data is available on their prognostic role. Aims of our study a) cross-sectional examination of the relationship between left ventricular mass index (LVMI), arterial vascular stiffness, and renal function, b) in our follow-up study, clarification of the LVMI, the prognostic role of AS in patients with CKD, IgA nephropathy (IgAN). Methods: In our cross-sectional study, 79 IgAN patients were examined in our clinic. The myocardial mass index (LVMI) was determined using an estimation formula after echocardiographic measurements. Arterial stiffness was measured using a photoplethizmography technique (PulseTrace) and characterized by the stiffness index (SI). The MDRD formula was used to estimate renal function (GFR) (eGFR, ml/min/1.73 m2). In the prognostic study the primary combined endpoint was total mortality, the most important CV events (stroke, myocardial infarction or cardiovascular interventions such as revascularization) and end stage renal disease. Secondary endpoints were CV and renal endpoints separately. Results: Of the 79 patients included in our cross-sectional study, 50 were men, with an average age of 46 ± 11 years. The mean value of LVMI was 106.66 ± 22.98 g/m2. Patients were divided into groups of 115 g/m2 for males considered to be abnormal and 95 g/m2 for women. LVMI is closely correlated with SI and inversely with eGFR (corr. coeff: 0.358; p <0.05 or -0.526; p <0.001). In case of LVH, SI was significantly higher in both sexes (p = 0.005 in males, p = 0.04 in females). In case of higher LVMI, renal function was significantly lower (p = 0.002 in males, p = 0.01 in females). Metabolic syndrome occurred in several cases in both sexes with LVH, but the difference was only significant in male patients (males 6 vs. 10, p = 0.008; females 2 vs. 4, p = 0.29). In our follow-up study, the presence of LVH in men significantly reduced survival in both primary and secondary endpoints, whereas in women there was no significant difference. Conclusion: In IgAN decreasing of renal function is closely related to left ventricular hypertrophy and vascular stiffness, as well as a close relationship was found between LVMI and AS. Reduced renal function is associated with an increase in LVMI and an increase in AS, which may result in a worse prognosis for both CV and renal outcomes. The underlying role of all these can be assumed to be a common vascular and myocardial pathological remodeling.]

Clinical Neuroscience

JANUARY 30, 2020

[Current questions of multiple sclerosis: the secunder progressive form of the disease]

VÉCSEI László

[Recent data suggest that long-term worsening is common in relapsing-remitting multiple sclerosis patients and is largely independent of relapses or new lesion formation on brain MRI. The current definition of secunder progressive multiple sclerosis is worsening of disability independent of relapses over at least 6-month interval. Early focal inflammatory disease activity and spinal cord lesion are predictors of very-long term disease outcomes in relapse - onset multiple sclerosis. The potential of PET imaging to visualize hidden inflammation in MS brain in vivo is an important contribution for better understanding the progression of the disease. Therefore, PET imaging is a promising tool in detecting the conversion from relapsing remitting multiple sclerosis to secunder progressive form of multiple sclerosis. Furthermore, neuro-axonal damage is the pathological substrate of permanent disability in different neurological disorders including multiple sclerosis. The neurofilament proteins have promise in this context because their levels rise upon neuro-axonal damage not only in the cerebrospinal fluid but also in blood. Patients with increased serum levels of neurofilament at baseline, independent of other clinical and MRI variables, experience significantly more brain and spinal cord volume loss over 2 years and 5 years of follow-up. The kynurenine-pathway abnormalities may be associated with the swich from early-mild stage multiple sclerosis to debilitating progressive forms of the disease. Analysis of these metabolites in serum may have application as multiple sclerosis disease biomarkers. Free radical action has been suggested as a causal factor in the illness. Increased free radical production and consumption of the scavenger molecules were found during the active phase of the disease. Based on the clinical findings (EXPAND Study) and pathomechanism of the disease siponimod is approved by the US Food and Drug Administration for the treatment of relapsing remitting forms of multiple sclerosis, to include secunder progressive multiple sclerosis with active disease, relapsing-remitting multiple sclerosis and clinically isolated syndrome.]

Clinical Oncology

APRIL 10, 2019

[Current views on the male breast cancer]

BAKI Márta

[Breast cancer in men is a rare disease, and accounts for only 1% of all diagnosed breast cancers. Hungarian incidence by available data much higher. The greatest risk factor of male breast cancer the elevated estrogen concentration in the body. Genetic disorders, as a Klinefelter syndrome and estrogen exposures and other metabolic changes might cause the male breast cancer. Symptom duration is longer than female population and the male breast cancers diagnosed in older ages and advanced stages. Frequency of BRCA2 mutation is probably 10% among male patients. The most common type is invasive ductal carcinoma with estrogen and progesterone receptor positivity. Diagnostic, surgical, radiation procedures and chemotherapy probably same as female breast cancer. The guidelines recommend as in adjuvant and curative setting the tamoxifen and other selective estrogen receptor modulators treatment. By large nation based registry the survival rate is different from male and female breast cancers. New biomarkers, genetic changes are under investigation to understand munch better the male breast cancer.]

Clinical Oncology

FEBRUARY 20, 2019

[Practical use of meta-analyses in predicting disease risk, outcome, and therapy response in breast cancer]

KAHÁN Zsuzsanna, TARI Gergely, ENYEDI Márton, HARACSKA Lajos

[Germinal BRCA status infl uences patient care both in early and advanced/metastatic breast cancer. Ideally, the patient should make the decision on the type of surgery or the avoidance of radiotherapy being aware of the BRCA status; based on the most recent clinical studies, this knowledge may infl uence the type of chemotherapy in the neoadjuvant, adjuvant, or metastatic setting or may raise the use of emerging targeted therapies. DNA-targeting cytostatic agents, mostly platinum agents and PARP inhibitors that act by inducing synthetic lethality, provide specifi c therapies in BRCA-mutant cases. The optimum place and sequence of these specifi c agents in treatment, however, are not known yet. International guidelines promote BRCA testing for the specifi cation of treatment strategy in all HER2-negative advanced/metastatic breast cancer cases (NCCN) or at least in all cases when, based on certain predictors, the presence of mutations is likely (ESMO). Recently, the methods employed for BRCA testing have improved immensely and are widely available through the services of various providers. For the identifi cation of the mutation, sequencing of the whole genes is needed, which can be achieved faster and more cost-effi ciently using next-generation sequencing (NGS) platforms compared to previous methods. It is the responsibility of the physician to consider the possibility of BRCA mutations and to raise the issue of BRCA testing to the patient if the family history, the age, previous malignant disease(s) of the patient, or the cancer features are suggestive of genetic risk.]

Clinical Oncology

FEBRUARY 20, 2019

[Practical use of meta-analyses in predicting disease risk, outcome, and therapy response in breast cancer]

MENYHÁRT Otília, GYŐRFFY Balázs

[Breast cancer is globally the most frequent malignant disease in women with increasing incidence. Meta-analyses using data from a large set of patients combining genetic and standard clinicopathological features provide valuable models in predicting disease risk, outcome and therapy response. With the advent of molecular technologies, the amount of available data generated for each tumor and each patient is growing exponentially. The increased data availability allows the development of new innovative systems enabling to discover more effective prognostic and predictive biomarkers. The goal of this review is to summarize meta-analyses that utilize data from countless patients to provide breast cancer risk prediction (Gail-model, Claus-model, BRCApro, IBIS, BOADICEA), and prediction of prognosis and expected therapy response (PREDICT, Magee). In the last part of the review we introduce online analytical tools (KMplot, ROCplot) developed to examine, rank and validate new prognostic and predictive biomarker candidates.]

Clinical Oncology

FEBRUARY 20, 2019

[Molecular subtypes and the evolution of treatment decisions in metastatic colorectal cancer]

RODRIGO Dienstmann, RAMON Salazar, JOSEP Tabernero

[Colorectal cancer (CRC) has clinically-relevant molecular heterogeneity at multiple levels: genomics, epigenomics, transcriptomics and microenvironment features. Genomic events acquired during carcinogenesis remain drivers of cancer progression in the metastatic setting. For example, KRAS and NRAS mutations defi ne a population refractory to EGFR monoclonal antibodies, BRAFV600E mutations associate with poor outcome under standard therapies and response to targeted inhibitors in combinations, while HER2 amplifi cations confer unique sensitivity to double HER2 blockade. Multiple rare gene alterations driving resistance to EGFR monoclonal antibodies have been described with signifi cant overlap in primary and acquired mechanisms, in line with a clonal selection process. In this context, sequential analysis of circulating tumor DNA has the potential to guide drug development in a treatment refractory setting. Rare kinase fusion events and complex alterations in genes involved in DNA damage repair have been described, with emerging evidence for targetability. On the other hand, transcriptomic subtypes and pathway activation signatures have also shown prognostic and potential predictive value in metastatic CRC. These markers refl ect stromal and immune microenvironment interactions with cancer cells. For example, the microsatellite instable (MSI) or POLE ultramutant CRC population is particularly sensitive to immune checkpoint inhibitors, while tumors with a mesenchymal phenotype are characterized by activation of immunosuppressive molecules that mandate stratifi ed development of novel immunotherapy combinations. In this manuscript we review the expanding landscape of targetable oncogenic alterations and signatures in metastatic CRC and discuss the clinical implementation of novel molecular diagnostic tests.]