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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

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

The applications of transcranial Doppler in ischemic stroke

FINNSDÓTTIR Herdis, SZEGEDI István, OLÁH László, CSIBA László

Background: This overview provides a summary of the applications of transcranial Doppler (TCD) in ischemic stroke. Results: A fast-track neurovascular ultrasound protocol has been developed for detecting occlusion or stenosis. The technique is more reliable in the carotid area than in the posterior circulation. By monitoring the pulsatility index the in­crea­sed intracranial pressure can be diagnosed. TIBI score was developed for grading residual flow. TCD has been shown to accurately predict complete or any recanalization. Regarding recanalization, TCD has a sensitivity of 92%, a specificity of 88%, a positive predictive value of 96%, a negative predictive value of 78% and an overall accuracy of 91%, respectively. Sonothrombolysis seemed to be a promising application but randomized controlled trials have shown that it does not improve clinical outcome. TCD examination can detect microembolic signals (MES) which are associated with an increased risk of stroke. Micro­em­boli were detected in symptomatic and asymptomatic carotid artery stenosis and during carotid endarterectomy. The number of microemboli can be decreased by antithrombotic therapy. Contrast en­chan­ced examination and Valsalva maneuver with continuous TCD monitoring can accurately screen for right-to-left shunt.

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.

Clinical Oncology

AUGUST 30, 2019

[Beyond second line therapy in patients with metastatic colorectal cancer: a systematic review]

D. Arnold, G. W. Prager, A. Quintela, A. Stein, S. Moreno Vera, J. Taieb

[Background: The optimal chemotherapeutic regimen for use beyond the second line for patients with metastatic colorectal cancer (mCRC) remains unclear. Materials and methods: We systematically searched the Cochrane Database of Systematic Reviews, EMBASE and Medline for records published between January 2002 and May 2017, and cancer congress databases for records published between January 2014 and June 2017. Eligible studies evaluated the effi cacy, safety and patient-reported outcomes of monotherapies or combination therapies at any dose and number of treatment cycles for use beyond the second line in patients with mCRC. Studies were assessed for design and quality, and a qualitative data synthesis was conducted to understand the impact of treatment on overall survival and other relevant cancer-related outcomes. Results: The search yielded 938 references of which 68 were included for qualitative synthesis. There was limited evidence to support rechallenge with chemotherapy, targeted therapy or both. Compared with placebo, an overall survival benefi t for trifl uridine/tipiracil (also known as TAS-102) or regorafenib has been shown for patients previously treated with conventional chemotherapy and targeted therapy. There was no evidence to suggest a difference in effi cacy between these treatments. Patient choice and quality of life at this stage of treatment should also be considered when choosing an appropriate therapy. Conclusions: These fi ndings support the introduction of an approved agent such as trifl uridine/tipiracil or regorafenib beyond the second line before any rechallenge in patients with mCRC who have failed second line treatment.]

Journal of Nursing Theory and Practice

DECEMBER 30, 2019

[Nutritional changes in the elderly]

NAGY-LŐRINCZ Zsuzsanna, ZÁMBÓ Leonóra, MARGARITOVITS Tijana, VARGA-NAGY Veronika, VARGA Anita, ZENTAI Andrea

[Since population ageing is one of the greatest problem of our time, we should aim not only to increase life expectancy but also healthy life years. Ageing is considered to be a normal biological process that can be characterized by the decline of body functions contributing to the age-related changes in nutrition as well. Although the process is not necessarily accompanied by pathological conditions (such as malnutrition, dehydration, obstipation, cognitive deterioration, fragility, polypharmacy), the evolving physiological changes undoubtedly increase the susceptibility to diseases and accidents. Elderly care should be adapted to the evolving changes, and should meet the person’s specific needs. ]

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.]

Hypertension and nephrology

SEPTEMBER 30, 2020

[Post-career development of cardiometabolic changes and hypertension in competitive athletes]

LELBACH Ádám, KÁNTOR Márk, KOLLER Ákos

[Regular physical activity is essential in delaying the aging processes (e.g. arterial remodelling – stiffening, metabolism, bodyweight), the beneficial effects of competitive sports – especially strength sports – according to the recent data of the literature are questionable. The beneficial effects of physical activity on the cardiovascular (CV) system are well known, however less is known regarding the delayed impacts of high intensity competitive sports on the CV system, especially after the sport career is over. This review summarizes the effects of active competitive sport and the post-career period on the cardiometabolic system with special attention to the systemic blood pressure and the development of metabolic syndrome. After sport career, the welldeveloped high performance cardiovascular- and metabolic system suddenly is much less used, but still supported by sport-level diet. It is well known that hypertension is a significant pathogenic factor in the development of cardiovascular diseases, characterized – among others – by reduced elasticity of large- and medium- sized vessels thereby importantly contributing to the development of systolic hypertension. Inflammation and thrombus formation both play an important role in the development of vascular injury and atherosclerosis. The increased tone of microvessels can impair the blood supply of certain organs, including the coronary circulation. It has been ample shown, that regular non-competitive, aerobic exercise activities are important factors in preventing hypertension. Such pathological changes become more evident after the development of post-career obesity, as well as the development of hypertension due to the activation of the renin-angiotensin system through sodium retention and other metabolic changes (increased glucose tolerance, insulin resistance, type II diabetes mellitus). It has been ample shown, that regular non-competitive, dynamic aerobic exercise activities are important factors in preventing hypertension. The frequency, intensity, type, and time (FITT) principle of exercise prescription is the first and common therapeutic approach, which represents the translation of cardiovascular basic science research results into hypertension treatment, thus can provide a personalized physical activity program/therapy according to medical needs not just for the post-career sportspersons, but the wide range of patients.]