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Clinical Neuroscience

JANUARY 30, 2020

Neurocognitive functions in patients with hepatitis C infection

HORVÁTH Gergely, KELETI Teodóra, MAKARA Mihály, UNGVARI S Gabor, GAZDAG Gábor

Background - With improving treatment options, more attention is being paid to the neurocognitive symptoms related to hepatitis C infection (HCI). While HCI-related neurocognitive impairments are frequently subclinical, they can influence patients’ quality of life and fitness to work. Objective - The aim of this study was to assess HCI patients’ neurocognitive functions and explore the correlations between disease variables and neurocognitive symptoms. Method - The study was conducted between January 1, 2013 and December 31, 2015. All patients with HCI were included in the study who were registered at the Hepatology Outpatient Clinic of Szent István and Szent László Hospitals, met inclusion criteria and volunteered to participate. Patients’ sociodemographic data and medical history were recorded in a questionnaire designed for the study. The 21-item Beck Depression Inventory was used to detect depressive symptoms. Six computerized tests were used to evaluate patients’ neuropsychological functions. Results - Sixty patients participated in the study. In comparison with general population standards, patients demonstrated poorer performance in several neurocognitive tests. Neuropsychological performance was correlated with age, sex, length of time since HCI diagnosis, Fibroscan score and the number of previous antiviral treatments. Conclusions - The study’s main finding is that compared to general population standards, patients with hepatitis C virus-related disease exhibit impaired neuropsychological functioning in visuomotor and visuospatial functions, working memory, executive functions, and reaction time. Executive functions and reaction time were the most sensitive indicators for the length and severity of disease. Deterioration in these functions has a major negative effect on work performance particularly in certain occupations.

Clinical Neuroscience

JANUARY 30, 2020

Review of electrode placement with the Slim Modiolar Electrode: identification and management

DIMAK Balazs, NAGY Roland, PERENYI Adam, JARABIN Andras Janos, SCHULCZ Rebeka, CSANÁDY Miklós, JÓRI József, ROVÓ László, KISS Geza Jozsef

Background - Several cochlear implant recipients experience functionality loss due to electrode array mal-positioning. The application of delicate perimodiolar electrodes has many electrophysiological advantages, however, these profiles may be more susceptible to tip fold-over. Purpose - The prompt realization of such complication following electrode insertion would be auspicious, thus the electrode could be possibly repositioned during the same surgical procedure. Methods - The authors present three tip fold-over cases, experienced throughout their work with Slim Modiolar Electrode implants. Implantations were performed through the round window approach, by a skilled surgeon. Standard intraoperative measurements (electric integrity, neural response telemetry, and electrical stapedial reflex threshold tests) were successfully completed. The electrode position was controlled by conventional radiography on the first postoperative day. Results - Tip fold-over was not tactilely sensated by the surgeon. Our subjects revealed normal intraoperative telemetry measurements, only the postoperative imaging showed the tip fold-over. Due to the emerging adverse perception of constant beeping noise, the device was replaced by a CI512 implant after 6 months in one case. In the two remaining cases, the electrode array was reloaded into a back-up sheath, and reinserted into the scala tympani successfully through an extended round window approach. Discussion - Future additional studies using the spread of excitation or electric field imaging may improve test reliability. As all of these measurements are still carried out following electrode insertion, real-time identification, unfortunately, remains questionable. Conclusion - Tip fold-over could be reliably identified by conventional X-ray imaging. By contrast, intraoperative electrophysiology was not sufficiently sensitive to reveal it.

Clinical Neuroscience

JANUARY 30, 2020

[The quality of life of the cluster headache patients during the active phase of the headache]

DIÓSSY Mária, BALOGH Eszter, MAGYAR Máté, GYÜRE Tamás, CSÉPÁNY Éva, BOZSIK György, ERTSEY Csaba

[Introduction - Cluster headache (CH), which affects 0.1% of the population, is one of the most painful human conditions: despite adequate treatment, the frequent and severe headaches cause a significant burden to the patients. According to a small number of previous studies, CH has a serious negative effect on the sufferers’ quality of life (QOL). In the current study, we set out to examine the quality of life of the CH patients attending our outpatient service between 2013 and 2016, using generic and headache-specific QOL instruments. Methods - A total of 42 CH patients (16 females and 26 males; mean age: 39.1±13.5 years) completed the SF-36 generic QOL questionnaire and the headache- specific CHQQ questionnaire (Comprehensive Headache- related Quality of life Questionnaire), during the active phase of their headache. Their data were compared to those of patients suffering from chronic tension type headache (CTH) and to data obtained from controls not suffering from significant forms of headache, using Kruskal-Wallis tests. Results - During the active phase of the CH, the patients’ generic QOL was significantly worse than that of normal controls in four of the 8 domains of the SF-36 instrument. Apart from a significantly worse result in the ‘Bodily pain’ SF-36 domain, there were no significant differences between the CH patients’ and the CTH patients’ results. All the dimensions and the total score of the headache-specific CHQQ instrument showed significantly worse QOL in the CH group than in the CTH group or in the control group. Conclusion - Cluster headache has a significant negative effect on the quality of life. The decrease of QOL experienced by the patients was better reflected by the headache-specific CHQQ instrument than by the generic SF-36 instrument. ]

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.]

Clinical Oncology

FEBRUARY 20, 2019

[Liquid biopsy in clinical oncology – fine-tuning precision medicine]

PRISKIN Katalin, PINTÉR Lajos, JAKSA Gábor, PÓLYA Sára, KAHÁN Zsuzsa, SÜKÖSD Farkas, HARACSKA Lajos

[The classical method of genetically characterising a tumour requires tissue biopsy with which a small sample is removed from the affected organ. This sample represents the tumour in the further analyses. However, the localised nature of sample collection limits representative characterisation. The so-called circulating tumour DNA, isolated from blood plasma after a simple sample collection, potentially enables the oncological analysis of all tumour tissues carrying genetic alterations that can be identifi ed as markers. In order to maximally exploit the potentials of circulating tumour DNA, we must adjust the analytical tools to its specifi c features. The preanalytical handling and storage of the sample signifi cantly infl uences its further usability. In order to be able to detect a potential mutation in a mostly wild-type background, the development of new, specifi c methods is needed, most of which are based on next-generation sequencing techniques. In the past decades, the pronounced decrease in the costs of such techniques led to an accumulation of an immense amount of genetic information on tumorigenesis. Due to the development of sequencing technologies, the turnaround times of tests also decreased enabling their employment in routine care besides research. Starting from our research, this can be realised via three approaches: technological development, the implementation of our already existing diagnostic methods in liquid biopsy, and the construction of well-planned disease-specifi c gene panels. Based on international trends and our experience in serum diagnostics, we are certain that liquid biopsy will become a central pillar of oncological screening and precision oncology in the near future.]

Clinical Oncology

DECEMBER 10, 2018

[Treatment of head and neck cancer]

KATONA Csilla, LANDHERR László

[Head and neck cancers cause worldwide a signifi cant problem in health care systems. Despite great advances in therapeutic modalities its prognosis has not changed in the past few decades. It is mainly caused by classical risk factors, like alcohol consumption and smoking, but in a signifi cant number of oropharyngeal cancers HPV infection plays a major role, which is associated with a new patient group characterized by a much better prognosis and therapeutic response. In the diagnostic phase staging examinations (CT scan, MRI, FDG-PET) are also involved which are necessary to multidisciplinary decision making. It can be largely infl uenced by the patient’s preference. The therapy is based on multimodality approach; surgery, radiotherapy, chemoirradiation, chemotherapy and the combination of these are used in early or locally advanced tumours. Targeted agents like EGFR inhibitors are partly used in the recurrent/metastatic setting or in combination with radiotherapy. Immun checkpoint inhibitors are new therapeutic options for pretreated, recurrent/metastatic patients and their role is under investigation in earlier therapeutic lines. Several clinical trials aim treatment desintensifi cation strategies in HPV positive tumours. Molecular genetic tests try to defi ne subgroups of patients to plan individualized treatment. Regarding the signifi cant functional and aesthetic damage of both disease and treatment, supportive care and rehabilitation are of great importance.]

Lege Artis Medicinae

DECEMBER 10, 2019

[World Pancreatic Day - Constant vigilance!]

ILLÉS Dóra, CZAKÓ László

[Pancreatic cancer (PaC) is a rare disease. However, it has one of the highest mortality worldwide. In Hungary both the incidence and mortality are among the highest in Europe. Surgery is the only curative method to treat PaC. Unfortunately, PaC is often diagnosed in its inoperative stage due to the asymptomatic/aspecific progression. Unfortunately, there is no effective screening method for PaC. This article aims to raise awareness of PaC risks and symp­tomps upon the World Pancreatic Cancer Day (21.11) which indicate investigations to diagnose PaC in an early stage, in favor of a better outcome of the disease. ]

Lege Artis Medicinae

DECEMBER 10, 2019

[The adverse effects of smoking on our respiratory system based on data of the Hungarian Public Health Screening 2010-2018 ]

KÉKES Ede, DAIKI Tenno, DANKOVICS Gergely, BARNA István

[The regular smoking with or without clinical symptoms causes structural changes in the lung tissue and this is reflected in res­pi­ratory function tests. During the last 9 years of Hungary's comprehesive health promotion screening (MÁESZ) between 2010 and 2018, spiro­metric examinations (PEF, FEV1, MEF25-75, FVC) were performed on 70822 women and 60187 men. We used the percentage of predictive values in the analysis to describe the deviation from normal. The carbon monoxide (eCO) content measurement of the exhaled air (in ppm) was performed on 24899 women and 22340 men. The COPD Evaluation Ques­tionnaire (CAT) was completed by 4166 wo­men and 3170 men. All four parameters of spirometry showed lower values for smokers in both sexes, but in men they were lower than in women. Ageing lowered significantly the values. The rate of changes from normal predictive values and the difference between smokers and non-smokers was the highest for MEF25-75 and FVC. The expiratory CO content (eCO) was significantly higher in smokers than in non-smokers in all age groups. In smokers, the incidence in percent of abnormal CAT score was significantly higher. Respiratory screening tests reveal the harmful effects of smoking, even without clinical symptoms, and indicate the risk of developing COPD.]

Lege Artis Medicinae

DECEMBER 10, 2019

[Explorative statistical analysis of numerous blood tests’ metabolic panel with rank-correlation ]

BRYS Zoltán, NAGY Erzsébet, MAGYAR Gábor, MOLNÁR D. László, KIS János Tibor

[INTRODUCTION AND AIM - During rou­tine blood panel testing, large amounts of bio­medical data are collected in Hungary and in all over the world. The aim of our - ethically approved - exploratory medical data analysis was to examine whether the analysis of correlations among several variables in a real-life, non-random blood panel data leads to meaningful results. DATA AND METHODS - In a retrospective study 2,292,199 anonymous routine blood panel data points were analyzed. Rank correlation was used between variables with more than 10,000 data points and strong (|ϱ|>0.5, p<0.001) relationships were visualized and interpreted. RESULTS - Similar laboratory values, effects of diseases affecting the same organ, as well as well-known medical interrelationships were shown between the examined laboratory parameter-pairs. DISCUSSION - Our exploratory data analysis shows that despite the non-random nature of the big blood panel sample, well-known medical correlations were very well detectable. Based on the results further re­search - with the inclusion of additional variables - seems reasonable and meaningful with due caution.]

Lege Artis Medicinae

NOVEMBER 15, 2019

[Specialists’ opinions about the introduction of colorectal cancer screening ]

MAGDA Lilla, TEREBESSY András

[ INTRODUCTION - The number of new cases of colorectal cancer is over 10 000 and there are around 5000 deaths per year in Hungary. A nationwide colon cancer screening program was launched in 2018. AIMS - Concerning the upcoming national screening, our aim was to explore attitudes, preferences and knowledge of specialists (family medicine, gastroenterology, surgery, oncology, pathology) who will be engaged in screening, diagnosis and treatment of colorectal cancer. METHOD - Before the start of the program we conducted semi-structured interviews with 20 representatives of specialties mentioned above. Interview-questions focused on knowledge (epidemiology, screening methods, program-related), preferences (screening method, protocol) and impact of the program on medical practice. Quan­ti­ta­tive and qualitative methods were used for analysis. RESULTS - Incidence of colon cancer was well known but its mortality in Hungary was underestimated. The public health significance of colorectal cancer scored 7 on a 10-point Likert scale and all participants agreed with introduction of the program. 12 people knew the chosen protocol (two-stage), only a single person mentioned one-stage (colonoscopy), and 7 had no information. 16 people prefer colonoscopy as the best screening method. 11 support two-stage protocol, 5 do not support but accept it, 4 would only accept the one-stage approach. 13 people think their duties will increase considerably. CONCLUSIONS - Our review partners consider colorectal screening in Hungary as an initiative to be supported. They expect increase of workload in their everyday medical practice and assume that the current endoscopic capacity will be overburdened. The majority prefers two-stage protocol because of cost-effectiveness while arguing that the colonoscopy has a bad reputation among the general population, nevertheless they consider colonoscopy as the best method of screening. ]