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Lege Artis Medicinae

OCTOBER 21, 2020

[Atherosclerosis: an ancient process in a new interpretation]

REIBER István

[The progress of atherosclerosis starts in childhood and lasts until the body dies. Most cardiovascular diseases and deaths can be traced back to atherosclerotic vascular changes. The process is thousands of years old, but its complex pathophysiology becomes recognized and realised only nowadays. Based on the evidence available today, atherosclerosis is such a chronic inflammatory disease of large- and medium-sized arteries, which is characterized by lipoproteins and immune cells transformed through oxidative and other changes and subendothelial accumulation of extracellular matrix. Innate and adaptive immunity provide a complex regulating system of atherogenesis, which while directing specifically the pro-atherogenic inflammatory and atheroprotective anti-inflammatory processes intensify plaque progression or even stabilize them respectively. With our growing knowledge about the pathology of atherogenesis, we can further improve the identification of cardiovascular risk conditions and apply more personalized therapeutic strategies.]

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.]

Journal of Nursing Theory and Practice

DECEMBER 30, 2019

[Perfusionist’s status in Hungary and the application of the low prime in coronary artery bypass]

DEÁK András, FUSZ Katalin, PRÉMUSZ Viktória, RAPOSA L. Bence, VÁRADYNÉ Horváth Ágnes, MADARÁSZ Ildikó, OLÁH András

[With the development of the equipments of extracorporeal circulation, international studies underline reducing the amount of filling fluid. Our retrospective study was conducted at the Heart Surgery Clinic of the University of Pécs between 1 January 2017 - 31 December 2017 with ECC cardiac operated patients. During the document analysis, data were collected from 157 patients between 50 and 70 years who underwent CAB surgery. They were classified into Low- (n=47) and Standard-prime (n=110) group. Medium negative correlation (r=-0.28; p<0.001) was found between prime/body surface area and haematocrit during last perfusion. As inflammatory parameter, the last measured CRP values were 36.00 mg/l (low) vs. 70.62 mg/l (standard). Our research justified the use of low-prime during ECC. The implementation of the method requires the scientific advancement of perfusionists, the preparation of national protocols and the improvement of the perfusionist’s training and legal background. ]

Hypertension and nephrology

NOVEMBER 04, 2020

[Hypertension and Covid-19 - part II.]

SZÉKÁCS Béla, KÉKES Ede, NAGY Judit, KOVÁCS Tibor

[The authors review those components and mechanisms in the two major regulatory systems of circulation and inflammation-coagulation whose internal balance and interactions are pathologically altered during SARS-CoV-2 infection, thereby enhancing lung and systemic inflammation threatening to enter into severe clinical condition. They examine the question of how – in addition to potentially promoting the coronavirus cellular entry and penetration – the RAS inhibitor therapy affects these changes and whether can be supposed difference between the anti-/pro-inflammatory influence of ACEi and ARB treatment of old hypertensive patients representing a remarkably high proportion of victims in COVID-19 epidemic. The paper is focussing to the pathomechanical background of inflammation beyond the direct immunological response to the infection: to the significance of immunological alterations characterizing old hypertensive patients also in basic condition, and to the key components as angiotensin II, ACE2, angiotensin1-7, bradykinin, ARB and ACEi. In conclusion a consideration on optimal point of action is offered in RASi treated and SARS-CoV-2 infected (old) hypertensive patients.]

Lege Artis Medicinae

OCTOBER 21, 2020

[Gene modified immune cells: New weapons not exclusively against cancer]

SZÖŐR Árpád

[The oncological breakthrough of the last decade was the application of CD19-specific CAR T cells in different hematologic diseases. Experience gained by clinical trials, coupled with investments of the private stakeholders and the pharmaceutical industry resulted not only in commercial release to the public of already developed CAR T cell products, but drew the atten­tion of many researchers to the potentials of new type immune cells, and their non-oncological administration. This study aims to present briefly those preclinical applications, which approved successfully the administration of CAR T cells in autoimmune and infectious diseases.]

Hypertension and nephrology

SEPTEMBER 30, 2020

[Treatment and care of hypertensive patients during and after the Covid-19 pandemic. Possibilities and effectiveness of telemedicine]

KÉKES Ede, SZEGEDI János, VÁLYI Péter

[The course and outcome of an pandemic caused by coronaviruses are determined by many factors, such as the strength and dose of the infectious virus, the immune system of the affected individual, the underlying diseases, the speed of virus spread, age and environmental factors and methods of control. In old age, there is a significantly higher risk of developing severe cases and fatalities. The rate of loss of life is particularly high in social care and nursing homes. Hypertension as the underlying disease is the most common cause of death, but hypertension alone is not an independence risk factor, but the main reason is the co-morbidities and complications associated with viral infection. In the epidemic situation, the treatment and care of hypertensive patients poses special challenges for health and active primary and specialist care workers and, of course, for hypertonologists. The Hungarian Society of Hypertension expressed its opinions and recommendations to patients living at home and to doctors performing treatment and care during the Covid-19 virus epidemic and summarized the decision-making possibilities derived from the data obtained during the telemedicine consultation. We would like to present the details of the possibilities provided by telemedicine, the practical possibilities and advantages of the different methods of teleconsultation, and the models that can be implemented in a domestic environment. We have taken into account international experience to date, the new e-health strategy for chronic, non-communicable diseases and the WHO concept. Telemedicine, continuous teleconsultation ensures an optimal relationship between the patient and the doctor, increases the patient’s sense of security, improves drug adherence. The doctor receives reliable data about the patient’s condition and can send him instructions as well as information. The development of a harmonious balance between personal contact and telecommunications already shows the future, and the application of these methods must be developed in the epidemic-free period as well. Previous international (TASMINH-4, HOMED-BP etc.) and domestic (CONADPER-HU) studies have proved that telemonitoring of hypertensive patients can be successfully solved, improves patients’ drug adherence, increases the target blood pressure achievement rate and at the same time the patient will be the active part of the treatment. The method is especially useful in rural settlements without a doctor. Telemedicine monitoring of elderly and multimorbid patients is especially useful in social institutions and nursing homes. It is solved the continuous control of vital functions, ensures continuity of contact with the supervising physician and in urgent cases, allows for rapid intervention. Telemedicine is also of great importance due to the lack of human resources, as many things can be solved with such technology, there are no need so many personal encounters. In addition to influencing the course of this pandemic, it also plays an important role in efficiency, headcount, management and “convenience” in general practice and in all formes of medicine. The proposed models can not only be applied in an epidemic situation, but should continue to be part of everyday health work in future.]

Clinical Neuroscience

SEPTEMBER 30, 2020

A rare entity of acquired idiopathic generalised anhidrosis which has been successfully treated with pulse steroid therapy: Does the histopathology predict the treatment response?

ÖKTEM Özdemir Ece, ÇANKAYA Şeyda, UYKUR Burak Abdullah, ERDEN Simsek Nazan, YULUG Burak

Acquired idiopathic generalised anhidrosis is an uncommon sweating disorder characterized by loss of sweating in the absence of any neurologic, metabolic or sweat gland abnormalities. Although some possible immunological and structural mechanisms have been proposed for this rare entity, the definitive pathophysiology is still un­clear. Despite some successfully treated cases with systemic corticosteroid application, the dose and route of steroid application are controversial. Here, we present a 41-year-old man with lack of genera­lised sweating who has been successfully treated with high dose pulse intravenous prednisolone. We have discussed his clinical and histopathological findings as well as the treatment options in view of the current literature.

Clinical Neuroscience

SEPTEMBER 30, 2020

Late simultaneous carcinomatous meningitis, temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting with mono-symptomatic vertigo – a clinico-pathological case reporT

JARABIN András János, KLIVÉNYI Péter, TISZLAVICZ László, MOLNÁR Anna Fiona, GION Katalin, FÖLDESI Imre, KISS Geza Jozsef, ROVÓ László, BELLA Zsolt

Although vertigo is one of the most common complaints, intracranial malignant tumors rarely cause sudden asymmetry between the tone of the vestibular peripheries masquerading as a peripheral-like disorder. Here we report a case of simultaneous temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting as acute unilateral vestibular syndrome, due to the reawakening of a primary gastric signet ring cell carcinoma. Purpose – Our objective was to identify those pathophysiological steps that may explain the complex process of tumor reawakening, dissemination. The possible causes of vestibular asymmetry were also traced. A 56-year-old male patient’s interdisciplinary medical data had been retrospectively analyzed. Original clinical and pathological results have been collected and thoroughly reevaluated, then new histological staining and immunohistochemistry methods have been added to the diagnostic pool. During the autopsy the cerebrum and cerebellum was edematous. The apex of the left petrous bone was infiltrated and destructed by a tumor mass of 2x2 cm in size. Histological reexamination of the original gastric resection specimen slides revealed focal submucosal tumorous infiltration with a vascular invasion. By immunohistochemistry mainly single infiltrating tumor cells were observed with Cytokeratin 7 and Vimentin positivity and partial loss of E-cadherin staining. The subsequent histological examination of necropsy tissue specimens confirmed the disseminated, multi-organ microscopic tumorous invasion. Discussion – It has been recently reported that the expression of Vimentin and the loss of E-cadherin is significantly associated with advanced stage, lymph node metastasis, vascular and neural invasion and undifferentiated type with p<0.05 significance. As our patient was middle aged and had no immune-deficiency, the promoting factor of the reawakening of the primary GC malignant disease after a 9-year-long period of dormancy remained undiscovered. The organ-specific tropism explained by the “seed and soil” theory was unexpected, due to rare occurrence of gastric cancer to metastasize in the meninges given that only a minority of these cells would be capable of crossing the blood brain barrier. Patients with past malignancies and new onset of neurological symptoms should alert the physician to central nervous system involvement, and the appropriate, targeted diagnostic and therapeutic work-up should be established immediately. Targeted staining with specific antibodies is recommended. Recent studies on cell lines indicate that metformin strongly inhibits epithelial-mesenchymal transition of gastric cancer cells. Therefore, further studies need to be performed on cases positive for epithelial-mesenchymal transition.

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.