Meconium aspiration syndrome: from pathophysiology to treatment.

Meconium aspiration syndrome (MAS) is a clinical condition characterized by respiratory distress in neonates born through meconium-stained amniotic fluid (MSAF). Despite advances in obstetric practices and perinatal care, MAS remains an important cause of morbidity and mortality in term and post-term newborns. Since the 1960s, there have been significant changes in the perinatal and postnatal management of infants born through MSAF. Routine endotracheal suctioning is no longer recommended in both vigorous and non-vigorous neonates with MSAF. Supportive care along with new treatments such as surfactant, inhaled nitric oxide, and high-frequency ventilation has significantly improved the outcome of MAS patients. However, determining the most appropriate approach for this condition continues to be a topic of debate. This review offers an updated overview of the epidemiology, etiopathogenesis, diagnosis, management, and prognosis of infants with MAS.

Less Invasive Surfactant Administration (LISA) Versus INSURE Method in Preterm Infants: a Retrospective Study.

Background: Respiratory distress syndrome (RDS) is a major cause of morbidity and mortality in preterm infants. Early nasal CPAP and selective administration of surfactant via the endotracheal tube are widely used in the treatment of RDS in preterm infants. Objective: The aim of this study was to compare the need for intubation and mechanical ventilation after surfactant delivery between LISA-treated and INSURE-treated premature infants with respiratory distress syndrome (RDS). Methods: Retrospective registry-based cohort study enrolled 36 newborns admitted to the neonatal intensive care unit of the "Santa Maria" Hospital of Terni between 2016 and 2023. As a primary outcome, we followed the need for intubation and mechanical ventilation within 72 hours of life, while the secondary outcomes were major neonatal morbidities and death before discharge. Results: The LISA group and the INSURE group included 13 and 23 newborns respectively. Demographic features showed no significant differences between the two groups. The need for mechanical ventilation in the first 72 hours of life was similar in both groups (p >0.99). There were no significant differences in morbidities. Conclusion: LISA and INSURE are equally effective modalities for surfactant administration for the treatment of RDS in preterm infants.

Cannabidiol: metabolism and clinical efficacy in epileptic patients.

INTRODUCTION: The landscape of epilepsy treatment has undergone a significant transformation with the emergence of cannabidiol as a potential therapeutic agent. Epidiolex, a pharmaceutical formulation of highly purified CBD, garnered significant attention not just for its therapeutic potential but also for being the first cannabis-derived medication to obtain approval from regulatory bodies. AREA COVERED: In this narrative review the authors explore the intricate landscape of CBD as an antiseizure medication, deepening into its pharmacological mechanisms and clinical trials involving various epileptic encephalopathies. This exploration serves as a comprehensive guide, shedding light on a compound that holds promise for individuals contending with the significant challenges of drug-resistant epilepsy. EXPERT OPINION: Rigorous studies highlight cannabidiol's efficacy, safety profile, and potential cognitive benefits, warranting further exploration for its approval in various drug-resistant epilepsy forms. As a promising therapeutic option, cannabidiol not only demonstrates efficacy in seizure control but also holds the potential for broader enhancements in the quality of life, especially for patients with epileptic encephalopathies.

NFIA haploinsufficiency: case series and literature review.

Background: NFIA-related disorder (OMIM #613735) is an autosomal dominant neurodevelopmental disorder characterized by a variable degree of cognitive impairment and non-specific dysmorphic features. To date, fewer than thirty patients affected by this disorder have been described. Methods: Our study included three children with NFIA haploinsufficiency recruited from three medical genetics centers. Clinical presentations were recorded on a standardized case report form. Results: All patients presented a variable degree of intellectual disability. None of the individuals in our cohort had urinary tract malformations. Three novel mutations, c.344G>A, c.261T>G, and c.887_888del are reported here. Conclusion: NFIA haploinsufficiency can be suspected through careful observation of specific dysmorphisms, including macrocephaly and craniofacial abnormalities. Instrumental tests such as MRI and renal ultrasound provide further diagnostic clues, while genetic testing can confirm the diagnosis.

Infective endocarditis caused by Gemella haemolysans in a patient with bicuspid aortic valve: A case report.

Gemella haemolysans is a gram-positive coccus, and commensal of the upper respiratory tract and oral mucosa. In rare cases, it has been identified as an opportunistic pathogen in the development of endocarditis. Here, we describe a case of Gemella haemolysans endocarditis in a patient with bicuspid aortic valve. A 14-year-old male presented to our hospital with a 1-month history of intermittent fever. Gemella haemolysans was isolated from the patient's blood cultures. Transesophageal echocardiography revealed severe aortic stenosis and a pseudoaneurysm of the mitral-aortic intervalvular fibrosa. The patient underwent aortic valve replacement with pseudoaneurysm of the mitral-aortic intervalvular fibrosa repair and remained symptom-free during follow-up. This case highlights the importance of considering atypical pathogens as causative agents of infective endocarditis.

Effect of melatonin on sleep quality and EEG features in childhood epilepsy: a possible non-conventional treatment.

Background: Sleep and epilepsy are characterized by a bidirectional relationship. Indeed, epilepsy predisposes to the development of sleep disorders, while sleep deprivation may exacerbate epilepsy. In addition, antiseizure medication can disrupt normal sleep architecture. Therefore, adequate sleep hygiene could lead to improvement in seizure control. The present study aimed to evaluate the effect of melatonin on seizure frequency, EEG tracing, and sleep in children with focal idiopathic epilepsy. Methods: This observation study evaluated the effect of 4 mg oral melatonin in ameliorating sleep-wake cycle, seizure frequency, and EEG features in children with focal idiopathic epilepsy of infancy. Twenty children were enrolled from September 2020 to August 2021. The study consisted of serial controls at enrollment (t0), at 3 months (t1), and at 6 months (t2) including neurological examination, questionnaire about sleep disturbances (CSHQ), and EEG. Results: A significant improvement in sleep quality and daytime sleepiness was observed after melatonin supplementation. Furthermore, we observed a noteworthy improvement in EEG tracing at t2 that exhibited a significant correlation with improvements in CSHQ scores. Conclusion: The studies conducted so far to evaluate the effect of melatonin in persons with epilepsy do not lead to definitive conclusions. Despite the small population sample and the study design, we report sleep and EEG improvement after melatonin administration in our cohort. Larger studies are needed to further study the neuroprotective and anticonvulsant properties of melatonin.

Reintroducing Fenfluramine as a Treatment for Seizures: Current Knowledge, Recommendations and Gaps in Understanding.

Despite the introduction of new anti-seizure medications in recent years, approximately one-third of the epileptic population continues to experience seizures. Recently, the anti-obesity medication fenfluramine (FFA) has been successfully repurposed, and it has received approval from various regulatory agencies for the treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome. The potential antiseizure effects of FFA were initially observed in patients with photosensitive epilepsy in the 1980s but it was not rigorously explored as a treatment option until 30 years later. This narrative review aims to provide an overview of the historical progression of FFA's use, starting from initial clinical observations to preclinical studies and, ultimately, successful clinical trials in the field of epilepsy.

The impact of anti-seizure medications on electroencephalogram (EEG) results.

INTRODUCTION: Despite recent advances in neuroimaging and genetics, electroencephalography (EEG) continues to play a central role in the diagnosis and management of epilepsy. One application of EEG is called pharmaco-EEG. This technique is highly sensitive in detecting the effects of drugs on brain functioning and shows potential in predicting the efficacy and tolerability of anti-seizure medications (ASMs). AREAS COVERED: In this narrative review, the authors discuss the most salient data concerning the effects of different ASMs on EEG. The authors aim to provide a clear and concise overview of the current state of research in this area, while also identifying opportunities for future investigation. EXPERT OPINION: To date, pharmaco-EEG does not appear to be clinically reliable for predicting treatment response in epilepsy, as the literature is limited by underreporting of negative results, a lack of controls in many studies and insufficient direct replication of previous findings. Future research should focus on controlled interventional studies, which are currently lacking.

Acute lymphoblastic leukemia relapse presenting with optic nerve infiltration.

Acute lymphoblastic leukemia is the most common childhood malignancy. Despite many advances in therapy, about 15%-20% of children with acute lymphoblastic leukemia experience a disease relapse. Isolated ocular relapse is relatively rare. A 14-year-old male with T-cell acute lymphoblastic leukemia in remission presented with sudden onset of right eye pain and visual acuity impairment. Fundoscopic examination of the eye and magnetic resonance imaging of the orbits were consistent with optic nerve infiltration. The patient was treated with salvage chemotherapy, orbital radiation and eventual bone marrow transplantation, with notable improvement in vision and regression of retinal and optic nerve findings. Optic nerve infiltration represents an ophthalmic emergency and requires urgent management. The use of radiation therapy is a helpful adjunct with systemic chemotherapy in obtaining disease remission.

Clinical spectrum and currently available treatment of type I interferonopathy Aicardi-Goutières syndrome.

BACKGROUND: Aicardi-Goutières syndrome (AGS) is a genetically determined disorder with a variable phenotype. Since the original description of AGS, advances in gene sequencing techniques have resulted in a significant broadening of the phenotypic spectrum associated with AGS genes, and new clinical pictures have emerged beyond the classic presentation. The aim of this review is to provide a comprehensive analysis of the clinical spectrum of AGS and report currently available treatments and new immunosuppressive strategies. DATA SOURCES: Literature reviews and original research articles were collected from databases, including PubMed and ClinicalTrials.gov. Relevant articles about AGS were included. RESULTS: The involvement of the nervous system certainly represents the major cause of mortality and morbidity in AGS patients. However, other clinical manifestations, such as chilblains, hepatosplenomegaly, and hematological disturbances, may lead to the diagnosis and considerably impact the prognosis and overall quality of life of these patients. Therapeutic approaches of AGS are limited to interventions aimed at specific symptoms and the management of multiple comorbidities. However, advances in understanding the pathogenesis of AGS could open new and more effective therapies. CONCLUSIONS: The over-activation of innate immunity due to upregulated interferon production plays a critical role in AGS, leading to multi-organ damage with the main involvement of the central nervous system. To date, there is no specific and effective treatment for AGS. New drugs specifically targeting the interferon pathway may bring new hope to AGS patients.

Epilepsy and Cognitive Impairment in Childhood and Adolescence: A Mini-Review.

Managing epilepsy in people with an intellectual disability remains a therapeutic challenge and must take into account additional issues such as diagnostic difficulties and frequent drug resistance. Advances in genomic technologies improved our understanding of epilepsy and raised the possibility to develop patients-tailored treatments acting on the key molecular mechanisms involved in the development of the disease. In addition to conventional antiseizure medications (ASMs), ketogenic diet, hormone therapy and epilepsy surgery play an important role, especially in cases of drugresistance. This review aims to provide a comprehensive overview of the mainfactors influencing cognition in children and adolescents with epilepsy and the main therapeutic options available for the epilepsies associated with intellectual disability.

Improving Therapy of Pharmacoresistant Epilepsies: The Role of Fenfluramine.

Epilepsy is among the most common neurological chronic disorders, with a prevalence of 0.5-1%. Despite the introduction of new antiepileptic drugs during recent years, about one third of the epileptic population remain drug-resistant. Hence, especially in the pediatric population limited by different pharmacokinetics and pharmacodynamics and by ethical and regulatory issues it is needed to identify new therapeutic resources. New molecules initially used with other therapeutic indications, such as fenfluramine, are being considered for the treatment of pharmacoresistant epilepsies, including Dravet Syndrome (DS) and Lennox-Gastaut Syndrome (LGS). Drug-refractory seizures are a hallmark of both these conditions and their treatment remains a major challenge. Fenfluramine is an amphetamine derivative that was previously approved as a weight loss drug and later withdrawn when major cardiac adverse events were reported. However, a new role of fenfluramine has emerged in recent years. Indeed, fenfluramine has proved to be a promising antiepileptic drug with a favorable risk-benefit profile for the treatment of DS, LGS and possibly other drug-resistant epileptic syndromes. The mechanism by which fenfluramine provide an antiepileptic action is not fully understood but it seems to go beyond its pro-serotoninergic activity. This review aims to provide a comprehensive analysis of the literature, including ongoing trials, regarding the efficacy and safety of fenfluramine as adjunctive treatment of pharmacoresistant epilepsies.

Corrigendum: Improving therapy of pharmacoresistant epilepsies: The role of fenfluramine.

[This corrects the article DOI: 10.3389/fphar.2022.832929.].

Biologic therapies for juvenile idiopathic arthritis-associated uveitis.

Juvenile idiopathic arthritis (JIA) is the most frequent rheumatic disease of childhood and uveitis is its most common extra-articular manifestation. JIA-associated uveitis (JIA-U) is one of the main causes of visual impairment in children and represents a major challenge for pediatrician and ophthalmologist, due to its insidious onset and sight-threatening complications. Topical glucocorticoids are the first line of treatment, followed by conventional disease-modifying anti-rheumatic drugs (DMARDs), usually methotrexate (MTX). In recent years, new biological drugs targeting specific molecules involved in disease pathogenesis, have significantly improved the prognosis of the disease, especially for cases refractory to conventional therapies. In this review we discuss the role of biological agents in JIA-U, focusing on cytokine blockers and cell-targeted therapies aimed to control ocular inflammation.

Performance Evaluation of Attribute-Based Encryption in Automotive Embedded Platform for Secure Software Over-The-Air Update.

This paper aims to show that it is possible to improve security for over the air update functionalities in an automotive scenario through the use of a cryptographic scheme, called "Attribute-Based-Encryption" (ABE), which grants confidentiality to the software/firmware update done Over The Air (OTA). We demonstrate that ABE is seamlessly integrable into the state of the art solutions regarding the OTA update by showing that the overhead of the ABE integration in terms of computation time and its storage is negligible w.r.t. the other overheads that are introduced by the OTA process, also proving that security can be enhanced with a minimum cost. In order to support our claim, we report the experimental results of an implementation of the proposed ABE OTA technique on a Xilinx ZCU102 evaluation board, which is an automotive-oriented HW/SW platform that is equipped with a Zynq UltraScale+ MPSoC chip that is representative of the computing capability of real automotive Electronic Control Units (ECUs).

A secure communication suite for underwater acoustic sensor networks.

In this paper we describe a security suite for Underwater Acoustic Sensor Networks comprising both fixed and mobile nodes. The security suite is composed of a secure routing protocol and a set of cryptographic primitives aimed at protecting the confidentiality and the integrity of underwater communication while taking into account the unique characteristics and constraints of the acoustic channel. By means of experiments and simulations based on real data, we show that the suite is suitable for an underwater networking environment as it introduces limited, and sometimes negligible, communication and power consumption overhead.

Secure cooperation of autonomous mobile sensors using an underwater acoustic network.

Methodologies and algorithms are presented for the secure cooperation of a team of autonomous mobile underwater sensors, connected through an acoustic communication network, within surveillance and patrolling applications. In particular, the work proposes a cooperative algorithm in which the mobile underwater sensors (installed on Autonomous Underwater Vehicles-AUVs) respond to simple local rules based on the available information to perform the mission and maintain the communication link with the network (behavioral approach). The algorithm is intrinsically robust: with loss of communication among the vehicles the coverage performance (i.e., the mission goal) is degraded but not lost. The ensuing form of graceful degradation provides also a reactive measure against Denial of Service. The cooperative algorithm relies on the fact that the available information from the other sensors, though not necessarily complete, is trustworthy. To ensure trustworthiness, a security suite has been designed, specifically oriented to the underwater scenario, and in particular with the goal of reducing the communication overhead introduced by security in terms of number and size of messages. The paper gives implementation details on the integration between the security suite and the cooperative algorithm and provides statistics on the performance of the system as collected during the UAN project sea trial held in Trondheim, Norway, in May 2011.