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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

[Neoadjuvant and palliative drug therapy for bladder cancer]

MARÁZ Anikó

[The survival of patients with muscle-invasive localized bladder cancer is more favorable if they receive neoadjuvant or adjuvant cisplatin-based chemotherapy before or after cystectomy. Based on the meta-analyses, in case of neoadjuvant cisplatin-based chemotherapy, the 5-year survival benefi t is 5-16%. The outcome is even more favorable in case of patients who respond well to neoadjuvant chemotherapy (pathological complete remission rate 12–50%). More than 3 months delay of cystectomy does not signifi cantly reduce the survival if chemotherapy is performed before the operation. Results of adjuvant phase III studies and meta-analyses are not so unambiguous as neoadjuvant data, but chemotherapy seems to infl uence favorably PD-L1 expression the survival, especially in case of pT3/4 and/or N+ (and high grade or margin positivity) cases. According to the recent publications, outcome data of patients have been effective in case of progression after platinum therapy, in or after second-line and in fi rst-line therapies for cisplatin ineligible, PD-L1 positive patients, respectively. Survival and tumor response data are very promising; in particular stages, they seem to be more effective than the previously administered chemotherapies. Current and ongoing trials are investigating the combinations of new remedies with other immunotherapeutic agents or chemotherapies as well as trying to identify biomarkers in order to further increase effectiveness.]

Clinical Oncology

FEBRUARY 28, 2020

[Non-surgical treatment of ovarian cancer]

PIKÓ Béla, LACZÓ Ibolya,, MARIK László

[The primary surgery with an optimal cytoreduction is an essential step during the treatment of the epithelial ovarian cancer because it determines the effectiveness of other therapeutic options as well. Immediately after the surgery a cytostatic infusion typically 40-42.5 degrees Celsius is pumped directly to the abdomen. During the systemic therapy the main point is the 6 months progression free survival because beyond this time the disease could be considered as platinum sensitive, inside this time as platinum refracter or resistant disease. The cytostatic treatment improved during the years from the alkylating agents through the platinum derivates to the administration of paclitaxel with several combinations of them and with more and more signifi cant results and less side effects. The most signifi cant targeted agents are the angiogenesis inhibitors (mainly the bevacizumab) and the PARP-inhibitors which prevents DNA repairs. In order to a PARP-inhibitor could be administered a platinum sensitivity is required while BRCA mutation not. Recently there are promising clinical researches with immunotherapy as well. The main benefi t of the hormonal therapy is the tolerability. Besides the signifi cant improvement in the systemic agents the role of radiotherapy is more and more decreasing, however the treatment of the whole peritoneal surface – mainly with the modern radiation techniques – could be an alternative solution for the chemotherapy. The palliative irradiation which relieve the symptoms could extend the drug-free period and the combination of radiation and chemotherapy could provide further possibilities.]

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

DECEMBER 30, 2019

[Systemic anticancer therapy in patients undergoing hemodialysis]

VÉGH Éva, LAKATOS Gábor, TOKODI Zsófia

[The number of cancer patients receiving regular dialysis treatment is increasing. These patients could benefi t similarly from the regular anticancer therapies. Data of the use of antineoplastic therapies in this vulnerable patient population mainly come from case reports and small case series. The lack of knowledge and lack of practical experiences in this patient group may lead to suboptimal cancer treatment. Defi ning the indication for antineoplastic treatment and choosing the appropriate drug is a challenging task and the patients’ prognosis and quality of life aspects should be evaluated carefully. The timing of anticancer treatment and the dialysis is also an important issue in this decision-making process. Close cooperation between the oncologists and nephrologists is essential in the proper antineoplastic treatment of the dialysed patients.]

Clinical Oncology

DECEMBER 30, 2019

[Sequential therapy of metastatic renal cell carcinoma]

TORDAY László

[The incidence of renal carcinoma is on the rise in developed countries, with the tumor being among the 10 most common malignancies. However, the survival of patients with irresecable renal carcinoma has improved signifi cantly in recent years, mainly due to signifi cant advances in oncology treatment. The use of agents acting on the VEGF and mTOR signaling pathways is widespread and has become a standard clinical practice in fi rst and later line therapy. Recent clinical trials have provided many new drugs with new targets (cMET and AXL, FGFR, PD-1/PD-L1, CTLA-4) and combinations thereof, and have completely redrawn the treatment landscape of metastatic renal carcinoma and signifi cantly improved clinical results. This report reviews data on targeted drug therapy of renal cell carcinoma and discusses the therapeutic position of various drugs and combinations to our knowledge.]

Clinical Oncology

AUGUST 30, 2019

[Prevention of drug-related neuropathy in the clinical practice]

VAJDICS Tímea

[There was a revolution of oncological treatments in the last fi ve years caused by introduction of immuncheckpoint inhibitors. Platinum and taxane based chemotherapies are the standard of care of the most frequent malignancies such as colon and breast cancer. Signifi cant improvement was achieved concerning side effects of chemotherapy in the few past decades. Preventive treatment of vomiting, neutropenia, aneamia are now based on clinical evidences. Meanwhile, there remained side effects (including chemotherapy induced neuropathy) which are diffi cult to treat. This article provides overwiev of the pharmacological therapies, vitamins and non-pharmacological procedures aimed to prevent chemotherapy induced neuropathy. Unfortunately still there are no drugs that are highly effective of preventing of chemotherapy induced periferial neuropathy validated in randomized clinical trials.]

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

[Epidemiology of diabetes mellitus and diabetes-related eye complications in Hungary]

TÓTH Gábor, NÉMETH János

[Diabetes mellitus is a disease of civilization and a leading cause of blindness among people of working age in developed countries. It’s prevalence is estimated to be 9.9% in the adult population in Hungary, based on this, the estimated number of people with diabetes mellitus was 807 000 in 2015 in our country. Almost every fifth people with diabetes mellitus has some form of diabetic retinopathy in Hungary. Among diabetic persons 0.3% is blind and 0.3% has serious visual impairment due to not adequately treated diabetes mellitus. The total prevalence-based diabetes retinopathy-associated economic burden was 43.66 billion HUF in 2018 in our country. The two major cost drivers were anti-VEGF injections and vitrectomies; they covered almost the four-fifths of the total cost among people with diabetes mellitus. We have to emphasize the importance of prevention, healthy nutrition and frequent sport activity in the fight against diabetes mellitus and overweight. With at least annually performed eye examinations in people with diabetes mellitus and timely treatment of diabetic retinopathy, visual impairment and blindness due to complications of diabetes mellitus can be prevented. ]

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.]