Second Generation of Antiepileptic Drugs and Oxidative Stress.

Epilepsy is a chronic disease of the central nervous system characterized by recurrent epileptic seizures. As a result of epileptic seizure or status epilepticus oxidants are excessively formed, which may be one of the causes of neuronal death. Given the role of oxidative stress in epileptogenesis, as well as the participation of this process in other neurological conditions, we decided to review the latest state of knowledge regarding the relationship between selected newer antiepileptic drugs (AEDs), also known as antiseizure drugs, and oxidative stress. The literature review indicates that drugs enhancing GABA-ergic transmission (e.g., vigabatrin, tiagabine, gabapentin, topiramate) or other antiepileptics (e.g., lamotrigine, levetiracetam) reduce neuronal oxidation markers. In particular, levetiracetam may produce ambiguous effects in this regard. However, when a GABA-enhancing drug was applied to the healthy tissue, it tended to increase oxidative stress markers in a dose-dependent manner. Studies on diazepam have shown that it exerts a neuroprotective effect in a "U-shaped" dose-dependent manner after excitotoxic or oxidative stress. Its lower concentrations are insufficient to protect against neuronal damage, while higher concentrations produce neurodegeneration. Therefore, a conclusion follows that newer AEDs, enhancing GABA-ergic neurotransmission, may act similarly to diazepam, causing neurodegeneration and oxidative stress when used in high doses.

Overcoming Steroid Resistance in Pediatric Acute Lymphoblastic Leukemia-The State-of-the-Art Knowledge and Future Prospects.

Acute lymphoblastic leukemia (ALL) is the most common malignancy among children. Despite the enormous progress in ALL therapy, resulting in achieving a 5-year survival rate of up to 90%, the ambitious goal of reaching a 100% survival rate is still being pursued. A typical ALL treatment includes three phases: remission induction and consolidation and maintenance, preceded by a prednisone prephase. Poor prednisone response (PPR) is defined as the presence of ≥1.0 × 109 blasts/L in the peripheral blood on day eight of therapy and results in significantly frequent relapses and worse outcomes. Hence, identifying risk factors of steroid resistance and finding methods of overcoming that resistance may significantly improve patients' outcomes. A mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK-ERK) pathway seems to be a particularly attractive target, as its activation leads to steroid resistance via a phosphorylating Bcl-2-interacting mediator of cell death (BIM), which is crucial in the steroid-induced cell death. Several mutations causing activation of MAPK-ERK were discovered, notably the interleukin-7 receptor (IL-7R) pathway mutations in T-cell ALL and rat sarcoma virus (Ras) pathway mutations in precursor B-cell ALL. MAPK-ERK pathway inhibitors were demonstrated to enhance the results of dexamethasone therapy in preclinical ALL studies. This report summarizes steroids' mechanism of action, resistance to treatment, and prospects of steroids therapy in pediatric ALL.

The use of the ERAS protocol in malnourished and properly nourished patients undergoing elective surgery: a questionnaire study.

INTRODUCTION: Enhanced recovery after surgery (ERAS) is a modern approach to perioperative management. This study aimed to evaluate compliance with certain aspects of the ERAS protocol in malnourished and properly nourished patients undergoing elective surgery. MATERIAL AND METHODS: A questionnaire study was conducted among 197 patients undergoing elective surgery at the university hospital. We divided patients into two groups according to nutritional status. RESULTS: The study's results showed that 67 patients (34%) lost weight before admission (the weight-loss group). Twenty-five participants (37%) in the weight-loss group and 15 patients (12%) in the preserved-weight group underwent surgery due to cancer ( P < 0.001). More patients in the weight loss group (45 of 67) than in the preserved-weight group (40 of 129, P < 0.001) limited their food intake a week before the surgery. The preserved-weight group participants were mobilized earlier than the weight-loss group ( P = 0.04). The median number of hours since drinking their last fluids and eating their last meals before the surgery were 12.2 hours and 25.4 hours for both groups, respectively. Only eight patients received preoperative carbohydrate loading. We found higher serum protein concentrations in the preserved-weight group (7.10 [0.5] vs. 6.92 [0.71], P = 0.023); however, white blood cell count was higher in the weight-loss group (7.85 (2.28) vs.7.10 (0.50), P = 0.04). Both groups were highly satisfied with their hospital treatments. CONCLUSIONS: Our study revealed relatively high malnutrition in patients undergoing elective surgery. As a standard of perioperative care in the studied centre, the ERAS protocol implementation level is low.

Genetic Disorders with Predisposition to Paediatric Haematopoietic Malignancies-A Review.

The view of paediatric cancer as a genetic disease arises as genetic research develops. Germline mutations in cancer predisposition genes have been identified in about 10% of children. Paediatric cancers are characterized by heterogeneity in the types of genetic alterations that drive tumourigenesis. Interactions between germline and somatic mutations are a key determinant of cancer development. In 40% of patients, the family history does not predict the presence of inherited cancer predisposition syndromes and many cases go undetected. Paediatricians should be aware of specific symptoms, which highlight the need of evaluation for cancer syndromes. The quickest possible identification of such syndromes is of key importance, due to the possibility of early detection of neoplasms, followed by presymptomatic genetic testing of relatives, implementation of appropriate clinical procedures (e.g., avoiding radiotherapy), prophylactic surgical resection of organs at risk, or searching for donors of hematopoietic stem cells. Targetable driver mutations and corresponding signalling pathways provide a novel precision medicine strategy.Therefore, there is a need for multi-disciplinary cooperation between a paediatrician, an oncologist, a geneticist, and a psychologist during the surveillance of families with an increased cancer risk. This review aimed to emphasize the role of cancer-predisposition gene diagnostics in the genetic surveillance and medical care in paediatric oncology.

Diagnostic and therapeutic approach to children with Nijmegen breakage syndrome in relation to development of lymphoid malignancies.

INTRODUCTION AND OBJECTIVE: Nijmegen breakage syndrome (NBS) is a rare chromosomal instability disorder. The majority of patients carry founder mutation in the NBN gene (c.657_661del5). Characteristic features of the NBS include progressive microcephaly, dysmorphic facial features, immunodeficiency, and high predisposition to malignancy with cumulative cancer incidence by the age of 20 years, and amounted to over 70%. The aim of study is to present the latest methods of diagnosis, potential cancer risk factors and treatment of lymphoid malignancies in children with NBS. REVIEW METHODS: To review the evidence using PubMed and Google Scholar search which included articles published between 2009-2021, focusing on articles published between 2013-2021. ABBREVIATED DESCRIPTION OF THE STATE OF KNOWLEDGE: The average delay in diagnosis of NBS ranges from 4-5 years. Neonatal screening of T-cell excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs) seems favourable in NBS. There are no specific protocols for the treatment of lymphoid malignancies in children with NBS, and full- dose chemotherapy is the most frequently applied method. Reducing the doses of chemotherapy does not significantly reduce the toxicity. Main cause of death is cancer progression and treatment-related mortality mostly associated with infectious complications. Patients with diagnosed cancer who received haematopoietic stem cell transplantation (HSCT) had significantly higher 20-year OS than those who did not (42.7% vs. 30.3%). SUMMARY: Further meta-analysis is essential to establish the best monitoring and treatment regimen in patients with NBS and lymphoid malignancies.

Recent Advances in Treatment Options for Childhood Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia is the most common blood cancer in pediatric patients. There has been enormous progress in ALL treatment in recent years, which is reflected by the increase in the 5-year OS from 57% in the 1970s to up to 96% in the most recent studies. ALL treatment is based primarily on conventional methods, which include chemotherapy and radiotherapy. Their main weakness is severe toxicity, which prompts dose reduction, decreases the effectiveness of the treatment, and, in some cases, can lead to death. Currently, numerous modifications in treatment regimens are applied in order to limit toxicities emerging from conventional approaches and improve outcomes. Hematological treatment of pediatric patients is reaching for more novel treatment options, such as targeted treatment, CAR-T-cells therapy, and immunotherapy. These methods are currently used in conjunction with chemotherapy. Nevertheless, the swift progress in their development and increasing efficacity can lead to applying those novel therapies as standalone therapeutic options for pediatric ALL.

Multiple sclerosis in a child with neurofibromatosis type I - clinical management of a challenging case.

A 13-year-old girl with neurofibromastosis (NF1) was admitted to the Department of Paediatric Haematology, Oncology and Transplantology due to progressive vision loss in September 2018. The patient was diagnosed with optic nerve gliomas and chemotherapy was initiated. During the treatment, the girl experienced muscle weakness in the lower limbs, and uncharacteristic lesions were detected in the spinal cord. Eventually, the girl was diagnosed with MS. The described case is one of the few reports of a child with coexisting NF1 and MS. The coincidence of these diseases is unusual and requires a multidisciplinary approach. Vision impairment in patients suffering from NF1 is typically associated with optic nerve gliomas, although it can be caused by other factors, such as MS, which is proven to have a higher prevalence in the NF1 population. Extensive ophthalmological diagnostics may not be conclusive, thus there is a need for the thorough neurological evaluation of patients with NF1 and visual deficits.