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Clinical Oncology

FEBRUARY 28, 2020

[Role of infl ammation in the carcinogenesis]

KOPPER László, TÍMÁR József

[Chronic infl ammation is an important promoter of the carcinogenesis of several cancer types and also an important contributor to mutagenicity beside the known carcinogens. Beside the continous regeneration of the affected epithelia chronic infl ammation provide a special microenvironment intra and extracellular environment which support malignant transformation and block emerging immune reactions. On the other hand, cancer is generating chronic infl ammation itself independent from its role in the carcinogenic process. It is due to cancer necrosis as well as to the production of infl ammatory cytokines. Cancer-induced infl ammatory reactions block antitumoral immune responses and continous monitoring of this process provide valuable clinical parameter of cancer progression.]

Clinical Oncology

DECEMBER 30, 2019

[Targeted and immune therapies for hepatocellular carcinoma: Predictions for 2019 and beyond]

MASATOSHI Kudo

[Systemic therapy for hepatocellular carcinoma (HCC) has markedly advanced since the survival benefi t of a molecular targeted agent, sorafenib, were demonstrated in the SHARP and Asia Pacifi c trials in 2007. Treatment options for patients with advanced HCC increased by sorafenib, and long-term survival for patients with advanced stage HCC has become possible to some extent. However, development of a more potent fi rst-line novel molecular targeted agent replacing sorafenib and a potent second-line agent after disease progression on or intolerant to sorafenib has been warranted because sorafenib lacks tumor shrinking/necrotizing effects and induces relatively severe adverse events such as hand foot skin reaction. Many agents in the 1st line and 2nd line setting were attempted to develop between 2007 and 2016, but all of these clinical trials failed. On the other hand, clinical trials of 4 agents (regorafenib, lenvatinib, cabozantinib, and ramucirumab) succeeded in succession in 2017 and 2018, and their use in clinical practice is possible (regorafenib and lenvatinib) or underway (cabozantinib and ramucirumab). Furthermore, all of 5 clinical trials of combination therapy with transcatheter chemoembolization (TACE) plus a molecular targeted agent failed to date, however, the combination of TACE and sorafenib (TACTICS trials) was reported to be successful and presented at ASCO in 2018. Phase 3 clinical trials of immune checkpoint inhibitors and a combination therapy of immune checkpoint inhibitors and molecular targeted agents are also ongoing, which suggests treatment paradigm of HCC in all stages from early, intermediate and advanced stage, is expected to be changed drastically in the very near future.]

Clinical Neuroscience

NOVEMBER 30, 2020

Positive airway pressure normalizes glucose metabolism in obstructive sleep apnea independent of diabetes and obesity

KABELOĞLU Vasfiye, SENEL Benbir Gulçin, KARADENIZ Derya

The relationship among obstructive sleep apnea syndrome (OSAS), type 2 diabetes mellitus (DM2) and obesity is very complex and multi-directional. Obesity and increased visceral fat are important perpetuating factors for DM2 in patients with OSAS. On the other hand, OSAS itself leads to obesity by causing both leptin and insulin resistance as a consequence of activation of the sympathetic nervous system. Risk for developing DM2 further increases in patients with OSAS and obesity. Data regarding effects of positive airway pressure (PAP) therapy, gold standard treatment for OSAS, on glycemic control were inconsistent due to variability in duration of and adherence to PAP therapy. In our cohort study we investigated effects of PAP treatment on glucose metabolism in normal-weighted non-diabetic OSAS patients, in obese non-diabetic OSAS patients, and in OSAS patients with DM2. We prospectively analyzed 67 patients diagnosed with OSAS and documented to be effectively treated with PAP therapy for three months. Apnea-hypopnea index was highest in the diabetic group, being significantly higher than in the normal-weighted group (p=0.021). Mean HOMA values were significantly higher in obese (p=0.002) and diabetic group (p=0.001) than normal-weighted group; the differences were still significant after PAP therapy. HbA1c levels were significantly higher in diabetic group compared to those in normal-weighted (p=0.012) and obese (p=0.001) groups. After PAP treatment, decrease in HbA1c levels were significant in normal-weighted (p=0.008), obese (p=0.034), and diabetic (p=0.011) groups. There was no correlation with the change in HbA1c levels and age (p=0.212), BMI (p=0.322), AHI (p=0.098) or oxygen levels (p=0.122). Our study showed that treatment of OSAS by PAP therapy offers beneficial effect on glucose metabolism, not only in diabetic patients, but also in obese and normal-weighted OSAS patients. Although data regarding overall effects of PAP therapy on glycemic control present contradictory results in the literature, it should be emphasized that duration and adherence to PAP therapy were main determinants for beneficial outcome of treatment.

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.]

Hypertension and nephrology

JUNE 24, 2020

[Comparison of kidney transplant patients with IR-tacrolimus and LCP-tacrolimus]

BORDA Bernadett

[Tremor is the most common adverse event of tacrolimus, and it correlates with the peak concentration of the drug. LCP-tacrolimus is a prolonged release formulation of tacrolimus to be administered once daily and has a dec - reased Cmax value. Hand tremors are evaluated by the Fahn-Tolosa-Marin (FTM) scale used by the neurologists. In case of hand tremor, tacrolimus is switched to LCP-tacrolimus. Tremor improved significantly in accordance with the STRATO cli - ni cal study, which confirmed that switching to LCP-tacrolimus resulted in clinically significant improvement in hand tremor.]

Clinical Neuroscience

JULY 30, 2020

[Objective measurement of manual dexterity of Parkinson patients operated with DBS]

SZÁNTÓ Ildikó, SÁNDOR Balázs, KATONA Krisztián, NAGY Máté, JUHÁSZ Annamária, BALÁS István

[The evaluation of hand dexterity is an important marker for the success of DBS (deep brain stimulation) operation in patients with Parkinson’s disease. In this study we applied a simple, semiquantitative optical dental plaque staining technique for the evaluation of the hand dexterity. Ten patient with Parkinson’s disease were involved in the study. After dental students aided tooth brushing, bacterial dental deposits (plaque) were stained then photographed, and quantified under standard conditions before and after DBS surgery. Our results showed a significant decrease in dental plaque deposits after DBS operation. This simple technique seems to be a routinely applicable marker for the evaluation of the hand dexterity. Our future plans is repeating the previous experiement on a higher number of cases.]

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

NOVEMBER 20, 2015

[A rare complication of a rare disease; stroke due to relapsing polychondritis]

KILIC COBAN Eda, XANMEMMEDOV Elimir, COLAK Melek, SOYSAL Aysun

[Relapsing polychondritis (RP) is an episodic and progressive inflammatory disease of cartilaginous structures. Its diagnosis is based primarily on clinical features such as laboratory parameters, biopsy. Neurological complications occur in 3% of the cases and are classified as an important cause of death. The cranial nerve disorders are most common but hemiplegia, ataxia, myelitis, polyneuritis, seizures, confusion, hallucination and headache can also happen. The aetiology of central nervous system involvement is still unknown. Moreover stroke has rarely reported in these patients. The diagnosis of stroke is challenging because of its rarity among these patients. Perhaps vasculitis is the common underlying mechanism. Also meningitis and encephalitis can occur during the course of RP. A 44 year-old woman was admitted with uncontemplated left hemiparesis, redness, swelling, and tenderness of the metacarpophalangeal and interphalangeal joints of the right hand and the cartilaginous portion. White blood cell count, C-reactive protein and the erythrocyte sedimentation rate were elevated. Vasculitis biomarkers were normal in our patient. Carotid and vertebral artery doppler ultrasonography, cranial and cervical MR Angiography were normal. Echocardiography showed a mild mitral valve prolapse and regurgitation. Our patient had the history of auricular polychondritis but she had not been diagnosed. Hemiparesis was her first neurological manifestation that led her to doctors for diagnosis. Our patient fulfilled the criteria of RP so no biopsy was needed. She was treated with oral prednisolone (80 mg/day) and aspirin (300 mg/day) and now she is on 10 mg prednisolone and 150 mg azathioprine. Two months later her physical and neurological symptoms returned to normal.]

Clinical Neuroscience

JANUARY 30, 2020

[Correction of the physiological artefacts at pre-surgical clinical functional MR]

KISS Máté, GÁL Andor Viktor, KOZÁK Lajos Rudolf, MARTOS János, NAGY Zoltán

[Introduction/aim of the study - Pre-surgical functional MRI (fMRI) is an important modality of examinations before brain surgery. There are several artefacts (e.g. motion, susceptibility) which may hinder the evaluation of fMRI data. Physiological artefacts (breathing, pulsation) also affect the sensitivity and specificity of anatomical localization. The aim of this study is to demonstrate the efficiency of physiological artefact identification and removal methods for presurgical evaluation. Materials and methods - Siemens Magnetom Verio 3T MRI scanner was used to collect data. The physiological parameters (breathing, pulse) were recorded with the MRI system’s built-in devices. Data from fourteen patients - with primary brain tumour - were evaluated with SPM12 utilizing the RETROICOR/RVHR tool to detect and decrease the effect of physiological artefacts. We compared the statistical maps obtained with and without the physiological correction using the Jaccard similarity coefficient, and ROI analyses. Results - Significant differences were found in the mean ROI values (p<0.0016) and the extensions of eloquent activations (p<0.0013), when using the physiological correction (RETORICOR/RVHR) based on convolution method. On the other hand, no significant differences were found between the ROIs’ standard deviations (F=0.28). The RETROICOR/ RVHR method helps to define the precise localisation of eloquent areas (p<0.009). The number of irrelevant (non-significant) voxels were increased (p<0.001). Conclusions - Minimising of physiological artefacts in fMRI data calculations, the (RETROICOR/RVHR) method based on convolution has been successfully adapted. This algorithm could be helpful before neurosurgical intervention. The activity pattern became more reliable. ]

Lege Artis Medicinae

JANUARY 20, 2020

[American-Hungarian forerunners of humanistic psychology and medicine: Andras Angyal and Bela Mittelmann ]

KELEMEN Gábor

[The fact that there are two significant Hungarian pioneers in humanistic psycho­therapy is still not recognised in the Hungarian academic community. In order to redress this omission the author compares and considers the careers of András Angyal and Béla Mittelmann. Both individuals left Hungary in 1920, settling first in Europe and subsequently in America, where they separately enjoyed successful careers. According to the author the trajectory of their lives is quite representative of many Hungarian emigrants during this period in history. This study examines the course of their life and explores their main achievements in the context of their contemporary relevance and enduring legacies. In the case of Angyal, it is the holistic-organismic theory of personality and influence on Maslow, which are his paramount achievements. As regards Mittelmann his topical contribution has been to the practice of “coaching” on the one hand and the application of dance and body therapy to recovery on the other. ]