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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 Neuroscience

MARCH 30, 2016

[Individual evaluation of loreta abnormalities in idiopathic generalized epilepsy]

CLEMENS Béla, PUSKÁS Szilvia, BESENYEI Mónika, KONKÁDOR István, HOLLÓDY Katalin, FOGARASI András, BENSE Katalin, EMRI Miklós, OPPOSITS Gábor, KOVÁCS Noémi Zsuzsanna, FEKETE István

[Background – Contemporary neuroimaging methods disclosed structural and functional cerebral abnormalities in idiopathic generalized epilepsies (IGEs). However, individual electrical (EEG) abnormalities have not been evaluated yet in IGE patients. IGE patients were investigated in the drug-free condition and after 3-6 month of antiepileptic treatment. To estimate the reproducibility of qEEG variables a retrospective recruited cohort of IGE patients was investigated. 19- channel resting state EEG activity was recorded. For each patient a total of 2 minutes EEG activity was analyzed by LORETA (Low Resolution Electromagnetic Tomography). Raw LORETA values were Z-transformed and projected to a MRI template. Z-values outside within the [+] 1. In drug-free condition, 41-50% of IGE patients showed abnormal LORETA values. 2. Abnormal LORETA findings showed great inter-individual variability. 3. Most abnormal LORETA-findings were symmetrical. 4. Most maximum Z-values were localized to frontal or temporal cortex. 5. Succesfull treatment was mostly coupled with disappearence of LORETA-abnormality, persistent seizures were accompanied by persistent LORETA abnormality. 1. LORETA abnormalities detected in the untreated condition reflect seizure-generating property of the cortex in IGE patients. 2. Maximum LORETA-Z abnormalities were topographically congruent with structural abnormalities reported by other research groups. 3. LORETA might help to investigate drug effects at the whole-brain level.]

Clinical Neuroscience

SEPTEMBER 30, 2019

[The role of epigenetic regulations in early childhood diseases]

TORY Vera

[With the acceptance of “The developmental origins of health and disease” concept in the 1990s, it became clear that epigenetic inheritance, which do not involve changes in the DNA sequence has important role in the pathogenesis of diseases. Epigenetic regulation serves the adaptation to the changing environment and maintains the reproductive fitness even on the drawback of increased risk of diseases in later life. The role of epigenetic mechanisms in chronic non-communicable diseases has been well established. Recent studies have revealed that epigenetic changes have also causal role in certain pediatric diseases. The review evaluates the recent epigenetic findings in the pathomechanism of common pediatric diseases. The wide range and long-lasting duration of epigenetic regulations give importance to the subject. Methods are already available to evaluate a part of the epigenetic changes in the clinical practice, presently aiming primarily the estimation of the disease risk or definition of diagnosis. Furthermore, there are already available limited means to influence the epigenetic regulation. ]

Lege Artis Medicinae

MAY 20, 2019

[Perinatal faulty hormonal imprinting: early impact, late consequences]

CSABA György

[The description and basic study of hormonal imprinting were the first in the series of research, which led to the recognition of the role of perinatal chemical effects in the late (adult age) manifestation of some diseases and inclination to diseases. Today it is clear, that certain pathological states, as obesity or diabetes, hypo- or hyperactivity (autoimmunity and allergy) of immune system can be deduced to perinatal (hormonal or metabolic) imprinting. The perinatal hormonal (chemical) imprinting takes place at the first encounter between the developing hormone receptor and the target hormone which sets the binding capacity of the receptor for life. In the critical periods of ontogeny (in addition to the perinatal imprinting) it can be developed at weaning, in adolescence and in continuously dividing and differentiating cells during the whole life. It is provoked by considerable quantitative differences of the physiological hormone or the presence of strange target-hormone-like molecules. The faulty hormonal imprinting leads to the adult-age diseases at any time of life and is inherited epigenetically to the progeny generations. Faulty hormonal imprinting always could be present in earlier times however, at present, because of the erroneous multiplication of endocrine disruptors in the environment, nutrition and medicine, its importance is continuously growing. The effects of faulty hormonal imprinting seem to be dangerous however, it can be imagined in the far future also a positive effect by the transformation of the human endocrine system at an evolutionary route. In the metabolic or immunological imprinting as well, as in the DOHaD (Developmental Origins of Health and Disease) the foremost recognized hormonal (chemical) imprinting is materialized.]

Lege Artis Medicinae

SEPTEMBER 20, 2018

[Feeding and eating in infancy and early childhood part III. - Development of self-feeding skills in the large-sample of the “For Healthy Offspring” project ]

NÉMETH Tünde, VÁRADY Erzsébet, DANIS Ildikó, SCHEURING Noémi, SZABÓ László

[Feeding and eating in infancy and early childhood part III. - Development of self-feeding skills in the large-sample of the “For Healthy Offspring” project INTRODUCTION - After introducing adequate complementary food to the diet of breastfed/formula-fed babies, the frequency and amount of semisolid/solid food is increasing, the breastmilk/formula intake is decreasing and finally the weaning process is completed. During this process the developing feeding skills of the infant enables them to self-feed. The self-feeding infant and toddler should participate in family meals. SUBJECTS AND METHODS - In the Healthy Offspring project self reported questionnaires were received from 1133 parents of 0-3 year old children. Issues concerning the development of self-feeding skills were analyzed. RESULTS - With advancing age the proportion of infants/toddlers, reported to be able to (partially) self-feed, has increased. The age, at which the majority of toddlers (83.1%) were reported to self-feed, was at 13-15 months. By the age over 2 years 57.2% of the toddlers were fully self-feeding, 39.3% were self-feeding with some assistance, and 3.5% were still completely fed by their mother/caregiver. While self-feeding became more prevalent, the proportion of toddlers with feeding problems and insufficient weight gain has increased. With more prevalent complementary feeding more parents assessed their feeding style rather scheduled than on demand. In the whole sample the proportion of infants/toddlers, who ate with the family, was 43.8%. CONCLUSIONS - In our sample, as previously described in the scientific literature, the developmental readiness to self-feed has developed in the majority of infants by the age of 13-15 months. During progres­sion of weaning an increasing proportion of parents thought, that feeding was rather scheduled than on demand. This finding points at the importance of educating parents about the importance of responsive feeding during and after weaning. For self-feeding toddlers, responsive feeding means, that the mother/caregiver offers a choice of healthy and adequate amount of food, at a proper place, at proper times, responds to the hunger and satiety cues of the child and the toddler decides, whether to eat, what and how much to eat.]

Lege Artis Medicinae

SEPTEMBER 20, 2018

[Differential diagnosis and treatment of hyponatraemia]

NÉMETH Zsófia, DEÁK György

[Hyponatraemia (serum sodium concentration < 136 mmol/l) is the most frequent electrolyte abnormality that inceases the risk of both in-hospital, and outpatient mortality. Antidiuretic hormone action or low glomerular fitration rate or low excretable osmoles or their combination are involved in its pathogenesis. Differential diagnosis is based on medical and medication histories, serum- and urine osmolality and urine sodium concentration. Measurement of fractional excretions of urea and uric acid help identifying low effective circulting volume, renal hypoperfusion. Symptomatic hyponatraemia or an acute decrease of serum sodium concentration exceeding 10 mmol/l should be treated with 3% NaCl to avoid impending threat to life. The principles of the treatment of chronic hyponatraemia are restriction of water intake and elimination of etiologic factor(s) (eg. medications - most often thiazides). In case of contracted axtracellular volume, isotonic saline should be given. In case of euvolaemia, restriciton of water intake is fundamental. In case of expanded extracellular volume, (heart failure, liver cirrhosis, nephrosis), water and NaCl intake should be restricted along with aldosteron antagonist and loop diuretic therapy. In chronic hyponatraemia, the rise of serum sodium concentration should not exceed 10 mmol/l during the first 24 hours and 8 mmol/l/day thereafter. ]

Clinical Neuroscience

MARCH 30, 2018

[Perinatal stroke - from symptoms to follow-up]

VOJCEK Eszter, CSÉCSEI Márta, FLACH Edina, RUDAS Gábor, GRÁF Rózsa, PRINCZKEL Erzsébet

[Background and purpose - We aimed to analyze patient characteristics of term neonates with the diagnosis of stroke between 2006 and 2017 at the 3rd level Neonatal Intensive Care Unit of the Szent János Hospital. Method - We conducted a retrospective and prospective analysis including 18 newborns with stroke. Presentation, imaging methods, etiology and clinical context were discussed. All patients had a follow-up at 2 years of age or later. Subject of the study - In the past 10 years 17 term born and one premature neonate born at 36 weeks of age were diagnosed with stroke in our unit. All patients were born at good condition generally with high Apgar scores (9±1). Cesarean section was performed in 4 cases. Results - With an estimated incidence of one in 1600-4000 births, the incidence of perinatal stroke in our unit was found to be the same as mentioned in the international databeses. Regarding imaging method, cranial ultrasound scan do not visualise arterial ischaemic stroke therefore head MRI is recommended. Neurological symptoms of the patients presented in the first two days of life. Etiology included thrombophilia (4/18), infection (4/18), vascular malformation (2/18), moderate asphyxia (2/18) and pre-eclampsia (2/18). Middle cerebral artery was involved in 50% while the anterior cerebral artery was affected in 33%. The stroke occured in the left hemisphaerium in 44%, in the right side in 39% and was bilateral in 17%. In two cases the stroke was diagnosed in utero. Early childhood developmental support resulted in average or above average gross and fine motor development and cognitive outcome. Conclusion - Presenting neurological symptoms tipically occur in the first few days after birth when perinatal stroke need to be considered among the broad spectrum of neonatal illnesses. Normal developmental outcome can be achieved even in cases of extensive brain damage with early childhood developmental support. Severely impaired development was observed in the cases of in utero stroke. Inherited prothrombotic disorders may have implications for subsequent pregnancies of the mother. ]

Journal of Nursing Theory and Practice

OCTOBER 30, 2017

[Importance of the Hyponatraemia in the Emergency Care]

PÓHR Kitti, KÖCSE Tamás, MESTERHÁZI András, BIERER Gábor, KARAMÁNNÉ Pakai Annamária

[The aim of the study: Hyponatraemia is the most common electrolyte abnormality in hospitalized patients. Certain drugs (eg, diuretics, antidepressants, and antiepileptics) have been implicated as established causes of either asymptomatic or symptomatic hyponatraemia. Studies proved correlation between hyponatremia and hospital mortality. Hyponatraemia remains asymptomatic in most cases, but if left untreated, it can cause life-threatening situations. Our aim was to examine the frequency of hyponatraemia in our hospital and its impact on the emergency care. Methods: A total of 75 patients were enrolled in the study with purposive sampling. We used descriptive and mathematical statistics with SPSS 22.0 software package for processing non-parametric statistical data. Results: Patients transferred by ambulance or arriving at the ER department came with dizziness, vomiting / diarrhea symptoms. Admission causes, were characteristic symptoms of hyponatraemia as well as non-specific neurological symptoms (headache, dizziness, confusion, unconsciousness) were found (n = 29). In addition, a common complaint of vomiting / diarrhea (n = 12), abdominal pain (n = 10). In particular, the complaint leading to a significant proportion of patients with hyponatraemia was not typical, but it was kind of trauma (n = 12). Nearly half of the patients (n = 36) were revenant. The most common diagnosis was hypertension (34%). 52% were taking medication that typically cause hyponatraemia. There were significant increase in the incidence of hyponatraemia in cases where the patient was taking diuretics. Conclusions: The diagnosis of hyponatraemia is based on the recording history, physical examination, and laboratory tests. Preventive approach would reduce the number of hospital stays due to hyponatraemia, and this may indeed improve patients’ life expectancy. The disease itself is easily remedied, it can cause critical condition due to disregard.]

Lege Artis Medicinae

JANUARY 20, 2018

[Is the evolvement of schizophrenia preventable?]

SZENDI István

[Considering the developmental nature of the majority of mental disorders, these days prevention has increasingly come into the focus of psychiatry. Schizophrenia - one of the disorders that are most frequently associated with psychosis, one of the most serious psychiatric syndromes - is the leading cause of permanent disability of the young adult generation. A prodrome lasting for several years precedes the onset of the first psychotic episode, which offers an opportunity for preventive interventions. Currently, we have two strategies for the predicition of the outburst of psychotic disorders. The Ultrahigh-risk approach can predict the first psychotic episode regardless of diagnosis, while the Basic symptom strategy predicts the development of schizophrenia specifically. However, there is an inverse relationship between the sensitivity and the specificity of different predictive criteria, which raises clinical and ethical dilemmas for the doctors. The methods of repeated assessments of the help-seeking individuals’ clinical states with designation of syndrome stages, and multivariate analyses of emprirically derived markers have proven promising tools for establishing more balance between the sensitivity and specificity of predictive criteria. Interven­tions of the secondary prevention aim to decrease the morbidity of the underlying pathomechanisms, and to help individuals’ coping with alterations of their experiences. We can consider here the psychosocial interventions as evidence based choices, which we can combine with certain food supplements and well-chosen psychopharmacons de­pending on the clinical state. With our in­terventions, we can influence the process of the individual development with vulnerable basis and steer it toward resilience. ]

Clinical Neuroscience

JULY 30, 2017

[Valproate in the treatment of epilepsy and status epilepticus]

JANSZKY József, TÉNYI Dalma, BÓNÉ Beáta

[According to Hungarian guidelines, valproate - with the exception of infants and small children as well as fertile women - is the first drug of choice in generalized and unclassified epilepsies because it is effective in most seizure types and epilepsy syndromes. It is highly effective in juvenile myoclonic epilepsy. Even though it is not the first-line drug in focal epilepsies, if the first-line therapy is ineffective, it is a plausible alternative as second choice therapy, owing to its different mechanism of action. If the type of epilepsy can’t be surely established, valproate is the drug of choice, as it possesses the broadest-spectrum among antiepileptic drugs. After administration of benzodiazepines, intravenously applied valproate can be a first choice therapy in all types of status epilepticus, owing to its broad-spectrum and efficacy. Valproate is the first-choice therapy in patients with glioblastoma - independently of the seizure type -, as it is likely to improve the survival rate with 2-10 months and the effectivity of chemo- and radiotherapy. Valproate is generally not suggested for fertile women, but - as it is the most effective therapy in some epilepsy syndromes -, the patient has the right to choose valproate therapy, thus undertaking the elevated risk of developmental abnormalities, for higher safety regarding seizures. If only valproate therapy owns the ability to obtain seizure freedom, then stopping its administration is not suggested, but a low dosage has to be aimed (500-600 mg/day, but not more than 1000 mg/day): according to some studies, most idiopathic generalized epilepsies can be controlled by low valproate dosage. Stopping valproate therapy in case of an ongoing pregnancy is not suggested. ]