Cystic Fibrosis and Oxidative Stress: The Role of CFTR.

There is substantial evidence in the literature that patients with cystic fibrosis (CF) have higher oxidative stress than patients with other diseases or healthy subjects. This results in an increase in reactive oxygen species (ROS) and in a deficit of antioxidant molecules and plays a fundamental role in the progression of chronic lung damage. Although it is known that recurrent infection-inflammation cycles in CF patients generate a highly oxidative environment, numerous clinical and preclinical studies suggest that the airways of a patient with CF present an inherently abnormal proinflammatory milieu due to elevated oxidative stress and abnormal lipid metabolism even before they become infected. This could be directly related to cystic fibrosis transmembrane conductance regulator (CFTR) deficiency, which appears to produce a redox imbalance in epithelial cells and extracellular fluids. This review aims to summarize the main mechanism by which CFTR deficiency is intrinsically responsible for the proinflammatory environment that characterizes the lung of a patient with CF.

PYRIDOXINE-dependent epilepsy (PDE): An observational study of neonatal cases on the role of pyridoxine in patients treated with standard anti-seizure medications.

BACKGROUND: The main objective of this study was to evaluate the neurological consequences of delayed pyridoxine administration in patients diagnosed with Pyridoxin Dependent Epilepsies (PDE). MATERIALS AND METHODS: We reviewed 29 articles, comprising 52 genetically diagnosed PDE cases, ensuring data homogeneity. Three additional cases were included from the General Pediatric Operative Unit of San Marco Hospital. Data collection considered factors like age at the first seizure's onset, EEG reports, genetic analyses, and more. Based on the response to first-line antiseizure medications, patients were categorized into four distinct groups. Follow-up evaluations employed various scales to ascertain neurological, cognitive, and psychomotor developments. RESULTS: Our study includes 55 patients (28 males and 27 females), among whom 15 were excluded for the lack of follow-up data. 21 patients were categorized as "Responder with Relapse", 11 as "Resistant", 6 as "Pyridoxine First Approach", and 2 as "Responders". The neurological outcome revealed 37,5 % with no neurological effects, 37,5 % showed complications in two developmental areas, 15 % in one, and 10 % in all areas. The statistical analysis highlighted a positive correlation between the time elapsed from the administration of pyridoxine after the first seizure and worse neurological outcomes. On the other hand, a significant association was found between an extended latency period (that is, the time that elapsed between the onset of the first seizure and its recurrence) and worse neurological outcomes in patients who received an unfavorable score on the neurological evaluation noted in a subsequent follow-up. CONCLUSIONS: The study highlights the importance of early recognition and intervention in PDE. Existing medical protocols frequently overlook the timely diagnosis of PDE. Immediate administration of pyridoxine, guided by a swift diagnosis in the presence of typical symptoms, might improve long-term neurological outcomes, and further studies should evaluate the outcome of PDE neonates promptly treated with Pyridoxine.

NRXN1 Deletion in Two Twins' Genotype and Phenotype: A Clinical Case and Literature Review.

In the literature, deletions in the 2p16.3 region of the neurexin gene (NRXN1) are associated with cognitive impairment, and other neuropsychiatric disorders, such as schizophrenia, autism, and Pitt-Hopkins-like syndrome 2. In this paper, we present twins with deletion 2p16.3 of the NRXN1 gene using a comparative genomic hybridization array. The two children had a dual diagnosis consisting of mild cognitive impairment and neurodevelopmental delay. Furthermore, they showed a dysmorphic phenotype characterized by facio-cranial disproportion, turricephalus, macrocrania, macrosomia, strabismus, and abnormal conformation of both auricles with low implantation. The genetic analysis of the family members showed the presence, in the father's genetic test, of a microdeletion of the short arm of chromosome 2, in the 2p16.3 region. Our case report can expand the knowledge on the genotype-phenotype association in carriers of 2p16.3 deletion and for genetic counseling that could help in the prevention and eventual treatment of this genetic condition. Newborn carriers should undergo neurobehavioral follow-ups for timely detection of warning signs.

Thrombotic events in children and adolescent patients with SARS-CoV-2 infection: a systematic review with meta-analysis on incidence and management.

OBJECTIVES: The present paper aimed to study the available literature on the hypercoagulability state of pediatric patients affected by COVID-19, and the current management of thrombosis in these patients, considering that no guidelines have been published since now in this age group. METHODS: N 244 titles were screened using the selected MESH words, 180 abstracts and 120 full texts were read, 12 articles were included, and four were analyzed by meta-analysis. RESULTS: Over 1128 COVID-19 positive patients, nearly half of them developed inflammatory sequelae, and 7.35% (40 patients over 544 who developed MIS-C) had thrombotic events. Less than 50% of patients with inflammatory disease were under anticoagulant prophylactic treatment, and doses of anticoagulant protocols vary from different centers. Thrombotic events prevented after the start of unfractionated heparin (UFH) therapy, even if 1.06% (4 patients) died. Only two patients presented complications after anticoagulant treatment, with non-fatal bleeding after UFH treatment. No other complications were reported. No difference in the incidence of thrombotic events between patients under prophylactic low molecular weight heparin (LMWH) and those without was found in meta-analysis (p = 0.32). CONCLUSIONS: Little is known on the incidence and management of hyper coagulopathy in pediatric COVID-19 infection. Further studies have to clarify this topic.

Neonatal neurologic emergencies requiring access to paediatric emergency units: a retrospective observational study.

Herein, authors present a retrospective, multi-center study to determine the number of accesses to Pediatric Emergency Unit (PEU) of patients within 28 days of life, admitted to (1) the Acute and Emergency Pediatric Unit, San Marco University Hospital, Catania, Italy; (2) Garibaldi Hospital for Emergency Care, Catania, Italy; (3) Cannizzaro Hospital for Emergency Care, Catania, Italy. We included neonates admitted for neurologic problems, from January 2015 to December 2020, to the 1-Acute and Emergency Access of the San Marco University Hospital, Catania, Italy [observation center 1 (OC1)]; 2-Garibaldi Hospital for Emergency Care, Catania, Italy (Observation Center 2-OC2); 3-Cannizzaro Hospital for Emergency Care, Catania, Italy (Observation Center 3-OC3). For each patient, we evaluated the severity of urgency, by studying the admission triage-coloured codes, the clinical data at admission and the discharge diagnosis. Neonates who had access to PEU were 812 in the OC1, 3720 in the OC2, and 748 in the OC3 respectively; 69 (8.4%), 138 (3.7%), and 55 (7.4%) was the proportion of neonatal accesses for neurological conditions. We observed that in the study period, the three hospitals had an important decrease of pediatric accesses to their PEU, but the proportion of neonates who had access to the OC1 for neurologic diseases, with respect to the total neonatal accesses, remained stable. We found that the most frequent neurologic disease for which newborns had access to PEU was Cyanosis, (46.1% of all neonatal accesses). Apnea was the second most frequent cause, with a number of 76 accesses (29%). In the literature there are numerous studies on the assessment of diseases that most frequently concern the pediatric patient in an emergency room, but there are very few references on neonatal accesses for urgent neurologic diseases. Therefore, appropriate training is required to avoid unnecessary tests without overlooking potentially serious conditions.