Early Screening for Long QT Syndrome and Cardiac Anomalies in Infants: A Comprehensive Study.

(1) Background: Sudden Infant Death Syndrome (SIDS) represents sudden and unexplained deaths during the sleep of infants under one year of age, despite thorough investigation. Screening for a prolonged QTc interval, a marker for Long QT Syndrome (LQTS), should be conducted on all newborns to reduce the incidence of SIDS. Neonatal electrocardiograms (ECGs) could identify congenital heart defects (CHDs) early, especially those not detected at birth. Infants with prolonged QTc intervals typically undergo genetic analysis for Long QT Syndrome. (2) Methods: The study involved infants aged 20-40 days, born with no apparent clinical signs of heart disease, with initial ECG screening. Infants with prenatal diagnoses or signs/symptoms of CHDs identified immediately after birth, as well as infants who had previously had an ECG or echocardiogram for other medical reasons, were excluded from the study. We used statistical software (SPSS version 22.0) to analyze the data. (3) Results: Of the 42,200 infants involved, 2245 were enrolled, with 39.9% being males. Following this initial screening, 164 children (37.8% males) with prolonged QTc intervals underwent further evaluation. Out of these 164 children, 27 children were confirmed to have LQTS. However, only 18 children were finally investigated for genetic mutations, and mutations were identified in 11 tests. The most common mutations were LQT1 (54.5%), LQT2 (36.4%), and LQT3 (1 patient). Treatment options included propranolol (39.8%), nadolol (22.2%), inderal (11.1%), metoprolol (11.1%), and no treatment (16.7%). The most common abnormalities were focal right bundle branch block (54.5%), left axis deviation (9.2%), and nonspecific ventricular repolarization abnormalities (7.1%). Multiple anomalies were found in 0.47% of children with focal right bundle branch block. Structural abnormalities were associated with specific features in 267 patients (11.9%), primarily isolated patent foramen ovale (PFO) at 61.4%. (4) Conclusions: This screening approach has demonstrated effectiveness in the early identification of LQTS and other cardiac rhythm anomalies, with additional identification of mutations and/or prolonged QTc intervals in family members. Identifying other ECG abnormalities and congenital heart malformations further enhances the benefits of the screening.

Exploring the Complex Interplay of Obesity, Allergic Diseases, and Sleep-Disordered Breathing in Children.

This narrative review study investigates the correlations between obesity, allergies, and sleep-disordered breathing in pediatric populations. Searches for pertinent articles were conducted on the Medline PubMed Advanced Search Builder, Scopus, and Web of Science databases from unlimited to April 2024. Sleep-disordered breathing causes repeated upper airway obstructions, leading to apneas and restless sleep. Childhood obesity, which affects around 20% of children, is often associated with sleep-disordered breathing and allergies such as asthma and allergic rhinitis. It is distinguished between diet-induced obesity (resulting from excess of diet and physical inactivity) and genetic obesity (such as is seen in Down syndrome and Prader-Willi syndrome). In children with diet-induced obesity, chronic inflammation linked to weight can worsen allergies and increase the risk and severity of asthma and rhinitis. Furthermore, the nasal congestion typical of rhinitis can contribute to upper respiratory tract obstruction and obstructive sleep apnea. A vicious circle is created between asthma and sleep-disordered breathing: uncontrolled asthma and sleep-disordered breathing can worsen each other. In children with genetic obesity, despite alterations in the immune system, fewer allergies are observed compared to the broader population. The causes of this reduced allergenicity are unclear but probably involve genetic, immunological, and environmental factors. Additional research is necessary to elucidate the underlying mechanisms. The present narrative review study emphasizes the importance of jointly evaluating and managing allergies, obesity, and obstructive sleep apnea in children considering their close interconnection.

Insights into Pediatric Sleep Disordered Breathing: Exploring Risk Factors, Surgical Interventions, and Physical and Scholastic Performance at Follow-Up.

(1) Background: Sleep-disordered breathing represents a growing public health concern, especially among children and adolescents. The main risk factors for pediatric sleep-disordered breathing in school-age children are tonsillar and adenoid hypertrophy. Adenoidectomy, often in combination with tonsillectomy, is the primary treatment modality for pediatric sleep-disordered breathing. This study aims to comprehensively investigate various risk and protective factors in children with sleep-disordered breathing undergoing adenotonsillar or adenoidal surgeries. We also aim to explore the differences in neuropsychological profiles. (2) Methods: This is an observational, retrospective cohort study. We collected information on adenoidectomy or adenotonsillectomy in children referred to our center. We reviewed the clinical history and preoperative visits and collected data through a telephone questionnaire. The Pediatric Sleep Questionnaire (PSQ) and the Pediatric Quality of Life Inventory (PedsQL) screen sleep-disordered breathing and quality of life, respectively. The data were statistically analyzed using SPSS version 22.0 for Windows (SPSS Inc., Chicago, IL, USA). (3) Results: The study involved 138 patients, but only 100 children participated. A higher percentage of patients with sleep-disordered breathing were observed to have mothers who smoked during pregnancy. A smaller proportion of patients with sleep-disordered breathing habitually used a pacifier. A rise in physical score was associated with a reduced PSQ at follow-up (p = 0.051). An increase in the overall academic score was related to a decrease in the PSQ at follow-up (p < 0.001). A more significant proportion of patients undergoing adenotonsillectomy were observed to have a history of prematurity and cesarean birth. (4) This comprehensive study delves into the intricate interplay of risk and protective factors impacting children with sleep-disordered breathing undergoing adenotonsillectomy and adenoidectomy.

Effects of the COVID-19 Pandemic on Brief Resolved Unexplained Events (BRUEs) in Children: A Comparative Analysis of Pre-Pandemic and Pandemic Periods.

BACKGROUND: Brief Resolved Unexplained Events (BRUEs), formerly known as Apparent Life-Threatening Events (ALTEs), are concerning episodes of short duration (typically <1 min) characterized by a change in breathing, consciousness, muscle tone, and/or skin color. In some cases, SARS-CoV-2 infection has been associated with episodes of BRUEs in previously healthy children. This study aimed to compare the demographic, respiratory, perinatal, and infectious characteristics in children affected by BRUEs before the COVID-19 pandemic and after the spread of SARS-CoV-2. METHODS: We conducted a retrospective observational study covering January 2018 to March 2020 (pre-COVID-19) and April 2023 (during the ongoing COVID-19 pandemic). Collected variables included clinical information during pregnancy and neonatal details of children with BRUEs. RESULTS: The number of children in the pre-COVID-19 period was 186 (41%); after the emergence and spread of SARS-CoV-2 this number was 268 (59%). The risk of infection at birth for children developing BRUEs was higher during the pandemic. Children were less likely to have ongoing symptomatic infection during BRUEs during the pandemic (coefficient B = 0.783; p = 0.009). Respiratory symptoms during BRUEs were more frequent during the pandemic (coefficient B = 0.654; p = 0.052). Fever during BRUEs was less likely during the pandemic (coefficient B = -0.465, p = 0.046). CONCLUSIONS: These findings could have significant clinical implications for managing children with BRUEs during the COVID-19 pandemic.

Association between individual sensor behavior of an electronic nose and airways inflammation in children with asthma: a pilot study at alpine altitude climate.

BACKGROUND: Markers of airway inflammation can be helpful in the management of childhood asthma. Residential activities, such as intensive asthma camps at alpine altitude climate (AAC), can help reduce bronchial inflammation in patients who fail to achieve optimal control of the disease. Analysis of volatile organic compounds (VOCs) can be obtained using electronic devices such as e-Noses. We aimed to identify alterations in urinary e-Nose sensors among children with asthma participating in an intensive camp at AAC and to investigate associations between urinary e-Nose analysis and airway inflammation. METHODS: We analyzed data collected in children with asthma recruited between July and September 2020. All children were born and resided at altitudes below 600 m asl. Urinary VOCs (measured using the Cyranose 320® VOC analyzer), Fractional exhaled Nitric Oxide (FeNO) and spirometry were evaluated upon children's arrival at the Istituto Pio XII, Misurina (BL), Italy, at 1756 m asl (T0), and after 7 (T1) and 15 days (T2) of stay. RESULTS: Twenty-two patients (68.2% males; median age: 14.5 years) were enrolled. From T0 to T1 and T2, the negative trend for FeNO was significant (p < .001). Significant associations were observed between e-Nose sensors S7 (p = .002), S12 (p = .013), S16 (p = .027), S17 (p = .017), S22 (p = .029), S29 (p = .021), S31 (p = .009) and ΔFeNO at T0-T1. ΔFeNO at T0-T2 was significantly associated with S17 (p = .015), S19 (p = .004), S21 (p = .020), S24 (p = .012), S25 (p = .018), S26 (p = .008), S27 (p = .002), S29 (p = .007), S30 (p = .013). CONCLUSIONS: We showed that a decrease in FeNO levels after a short sojourn at AAC is associated with behaviors of individual urinary e-Nose sensors in children with asthma.

Cardiac Implications of Adenotonsillar Hypertrophy and Obstructive Sleep Apnea in Pediatric Patients: A Comprehensive Systematic Review.

This review investigates the relationship between pediatric obstructive sleep apnea, often associated with adenotonsillar hypertrophy, and cardiovascular health, particularly pulmonary hypertension. We conducted a comprehensive literature search using electronic databases, including Medline Pub-Med, Scopus, and the Web of Science. The study analyzed a total of 230 articles and screened 48 articles, with 20 included in the final analysis, involving 2429 children. The PRISMA flowchart visually illustrates the selection process, and the ROBINS-E and -I tools help ensure the reliability and validity of the evidence produced by these studies. These studies explored various aspects, including the severity of obstructive sleep apnea, cardiac anomalies, cardiac stress markers, risk factors for pulmonary hypertension, and the impact of adenoidectomy and tonsillectomy on cardiac function. The research found that adenotonsillar hypertrophy and obstructive sleep apnea are significant risk factors for cardiovascular complications, especially pulmonary hypertension, in children. Adenoidectomy and tonsillectomy may provide effective treatments. Following adenoidectomy in relation to obstructive sleep apnea, there appears to be a reduction in mean pulmonary artery pressure during echocardiographic examination. However, the efficacy of these procedures can vary based on the severity of obstructive sleep apnea and individual cardiac conditions. The study also identified concerns regarding data bias. The authors emphasize the need for well-designed clinical studies, including both healthy patients with adenotonsillar hypertrophy and vulnerable children with genetic disorders, to ensure that clinical decisions are based on solid scientific evidence.

Pediatric Ocular Health and Obstructive Sleep Apnea Syndrome: A Review.

Obstructive sleep apnea (OSA) affects neurobehavioral, cognitive, and cardiovascular aspects, particularly in children, by obstructing the upper airways during sleep. While its impact in adult ocular health is recognized, there is ongoing debate about OSA's relevance in pediatrics. This review explores the relationship between OSA and ocular health in children, focusing on the effects and potential improvements through treatment. A systematic search found 287 articles through PubMeD/MEDLINE, Scopus, Web of Science, and ScienceDirect; 94.4% were excluded. After careful selection, six English articles were included, addressing the effects of OSA on children's eyes. Three studies examined choroidal alterations, three explored retinal and optic nerve changes, and two analyzed ocular changes following otorhinolaryngological intervention. The immediate correlation in children is inconclusive, but age may be a contributing factor. Pediatric OSA patients exhibit corneal anomalies and increased optic nerve thickness, possibly due to intermittent hypoxia. OSA influences retinal vascular density in children, with increased density after treatment and reduced choroidal thickness in cases of adenotonsillar hypertrophy. This review emphasized OSA's significant impact on children's ocular health, revealing alterations in the optic nerve, choroid, retina, and cornea. While the direct correlation with the optic nerve is not always evident, OSA raises intraocular pressure and induces structural changes. Treatment holds promise, highlighting the need for regular monitoring to promptly address childhood OSA.

Sleep Disordered Breathing in Children with Autism Spectrum Disorder: An In-Depth Review of Correlations and Complexities.

Sleep-disordered breathing is a significant problem affecting the pediatric population. These conditions can affect sleep quality and children's overall health and well-being. Difficulties in social interaction, communication, and repetitive behavioral patterns characterize autism spectrum disorder. Sleep disturbances are common in children with ASD. This literature review aims to gather and analyze available studies on the relationship between SDB and children with autism spectrum disorder. We comprehensively searched the literature using major search engines (PubMed, Scopus, and Web of Science). After removing duplicates, we extracted a total of 96 records. We selected 19 studies for inclusion after a thorough title and abstract screening process. Seven articles were ultimately incorporated into this analysis. The research findings presented herein emphasize the substantial influence of sleep-disordered breathing on pediatric individuals diagnosed with autism spectrum disorder (ASD). These findings reveal a high incidence of SDB in children with ASD, emphasizing the importance of early diagnosis and specialized treatment. Obesity in this population further complicates matters, requiring focused weight management strategies. Surgical interventions, such as adenotonsillectomy, have shown promise in improving behavioral issues in children with ASD affected by OSA, regardless of their obesity status. However, more comprehensive studies are necessary to investigate the benefits of A&T treatment, specifically in children with ASD and OSA. The complex relationship between ASD, SDB, and other factors, such as joint hypermobility and muscle hypotonia, suggests a need for multidisciplinary treatment approaches. Physiotherapy can play a critical role in addressing these intricate health issues. Early sleep assessments and tailored weight management strategies are essential for timely diagnosis and intervention in children with ASD. Policy initiatives should support these efforts to enhance the overall well-being of this population. Further research is crucial to understand the complex causes of sleep disturbances in children with ASD and to develop effective interventions considering the multifaceted nature of these conditions.

The Impact of Growth Hormone Therapy on Sleep-Related Health Outcomes in Children with Prader-Willi Syndrome: A Review and Clinical Analysis.

This literature review of growth hormone (GH) therapy and sleep-related health outcomes in children diagnosed with Prader-Willi syndrome (PWS) assembles evidence for the consequences of sleep deprivation and poor sleep quality: difficulty concentrating and learning at school, behavioral problems, diminished quality of life, and growth impairment. Sleep-disordered breathing (SDB) is another factor that impacts a child's well-being. We searched the electronic databases Medline PubMed Advanced Search Builder, Scopus, and Web of Science using MeSH terms and text words to retrieve articles on GH deficiency, recombinant human growth hormone (rhGH) therapy, sleep quality, SDB, and PWS in children. The censor date was April 2023. The initial search yielded 351 articles, 23 of which were analyzed for this review. The study findings suggest that while GH may have a role in regulating sleep, the relationship between GH treatment and sleep in patients with PWS is complex and influenced by GH dosage, patient age, and type and severity of respiratory disorders, among other factors. GH therapy can improve lung function, linear growth, and body composition in children with PWS; however, it can also trigger or worsen obstructive sleep apnea or hypoventilation in some. Long-term GH therapy may contribute to adenotonsillar hypertrophy and exacerbate sleep apnea in children with PWS. Finally, GH therapy can improve sleep quality in some patients but it can also cause or worsen SDB in others, leading to diminished sleep quality and overall quality of life. The current evidence suggests that the initial risk of worsening SDB may improve with long-term therapy. In conclusion, rhGH is the standard for managing patients with PWS. Nonetheless, its impact on respiratory function during sleep needs to be thoroughly evaluated. Polysomnography is advisable to assess the need for adenotonsillectomy before initiating rhGH therapy. Close monitoring of sleep disorders in patients with PWS receiving GH therapy is essential to ensure effective and safe treatment.

Exploring the Intricate Links between Adenotonsillar Hypertrophy, Mouth Breathing, and Craniofacial Development in Children with Sleep-Disordered Breathing: Unraveling the Vicious Cycle.

Adenotonsillar hypertrophy has been well-acknowledged as the primary instigator of sleep-disordered breathing in the pediatric population. This condition spans a spectrum, from typical age-related growth that the immune system influences to persistent pathological hypertrophy. Reduction in air spaces, metabolic changes, neurobehavioral alterations, and chronic inflammation characterizes the latter form. As the go-to treatment, adenotonsillectomy has proven effective. However, it is not a guarantee for all patients, leaving us without reliable predictors of treatment success. Evidence suggests a connection between adenotonsillar hypertrophy and specific oral breathing patterns resulting from craniofacial development. This finding implies an intricate interdependence between the two, hinting at a self-sustaining vicious cycle that persists without proper intervention. The theories regarding the relationship between craniofacial conformation and sleep-disordered breathing have given rise to intriguing perspectives. In particular, the "gracilization theory" and the "gravitational hypothesis" have provided fascinating insights into the complex interaction between craniofacial conformation and SDB. Further investigation is crucial to unraveling the underlying pathophysiological mechanisms behind this relationship. It is also vital to explore the risk factors linked to adenotonsillectomy failure, study the long-term effects of adenotonsillar hypertrophy on craniofacial growth, and devise innovative diagnostic techniques to detect upper airway compromise early. Moreover, to assess their efficacy, we must delve into novel therapeutic approaches for cases that do not respond to traditional treatment, including positional therapy and orofacial myofunctional therapy. Though complex and unpredictable, these challenges promise to enhance our understanding and treatment of adenotonsillar hypertrophy and its related complications in children. By taking on this task, we can pave the way for more effective and targeted interventions, ultimately improving affected individuals' well-being and quality of life.

Lung abscess as a complication of Lemierre Syndrome in adolescents: a single center case reports and review of the literature.

BACKGROUND: Fusobacterium necrophorum is an anaerobic, gram-negative, non-motile, filamentous, non-spore forming bacillus found in the oral cavity, gastrointestinal tract, and female genital tract, responsible of a rare disease named Lemierre Syndrome, characterized by septic thrombophlebitis of the internal jugular vein, which mainly affects previously healthy adolescents and young adults; some risk factors are reported, as smoking or primary viral or bacterial infection leading to the disruption of mucosa. The syndrome originates commonly from an upper respiratory infection such as pharyngotonsillitis, acute otitis media, cervical lymphadenitis, sinusitis, or odontogenic abscess, and may result in multiorgan metastasis, more frequently leading to pulmonary complications, especially lung abscesses. CASE PRESENTATION: We describe two cases of adolescents with atypical Lemierre Syndrome evaluated in a tertiary care center, one with a confirmed infection by Fusobacterium necrophorum and one with a presumptive diagnosis based on clinical features, who developed lung abscesses needing a prolonged antibiotic course and hospitalization. Of interest, both were user of electronic cigarette, configuring a possible new risk factor. The proper diagnosis of Lemierre Syndrome is often difficult to establish, so a high degree of suspicion is needed, especially in the case of lung abscesses in otherwise healthy adolescents. CONCLUSION: The current study will contribute to providing insight into Lemierre Syndrome clinical presentation and management in adolescents, promoting awareness for a rare but potentially fatal disease. Moreover, it suggests a possible relationship between Lemierre syndrome and the use of electronic cigarette, that should be investigated by future studies.

Unveiling the Hidden Connection between Allergies and Sleep-Disordered Breathing in Children and Its Impact on Health.

Sleep-disordered breathing (SDB) and allergies in children are increasingly relevant health issues that require attention [...].

Mental Health and Cognitive Development in Symptomatic Children and Adolescents Scoring High on Habitual Snoring: Role of Obesity and Allergy.

BACKGROUND: Obstructive sleep apnea can have a negative impact on children's and adolescents' neurocognitive abilities and hinder their academic and adaptive progress in academic, social, and/or behavioral dimensions. In this retrospective cross-sectional study, we investigated the influence of body weight conditions and allergy status on long-term mental health, cognitive development, and quality of life in children and adolescents who snored. METHODS: The study sample included 47 subjects (age range 4.1 to 15.3 years) who exhibited high levels of snoring and underwent home-based polysomnography between 2015 and 2019. Follow-up assessments (3 years on average between baseline and follow-up) entailed phone interviews with the subject's parents/caregivers who completed three validated questionnaires investigating sleep, quality of life, and parental ratings. RESULTS: We found a correlation between age at diagnosis and being retrospectively overweight and high levels of snoring. In addition to a higher risk of developing emotional symptoms (8.2% increase in retrospective overweight status for each unit increase in the emotional score at follow-up) and oppositional behavior (9% increase in retrospective overweight status for each unit of oppositional T points at follow-up), we also noted reduced long-term social symptoms (11% decrease in retrospective overweight status for each unit increase in the social score at follow-up) and cognitive symptoms (10.6% decrease in retrospective overweight status for each unit increase in the cognitive score at follow-up), as well as a 6.1% increase in retrospective allergy status for each unit increase in academic performance at follow-up. CONCLUSIONS: Snoring can have negative impacts on mental health and cognitive development in the long term. Early detection and intervention for neuropsychological disorders is important in children and adolescents who score high on snoring. In the long term, the effects of snoring on neuropsychological disorders may vary based on previous body weight and allergy status.

Allergic Diseases and Childhood Obesity: A Detrimental Link?

Several epidemiological studies have described childhood obesity as a risk factor for atopic disease, particularly asthma. At the same time, this association seems to be more conflicting for allergic rhinitis, atopic dermatitis, and chronic urticaria. This article aims to deepen the possibility of a relationship between childhood obesity and allergic diseases. As regards asthma, the mechanical and inflammatory effects of obesity can lead to its development. In addition, excess adiposity is associated with increased production of inflammatory cytokines and adipokines, leading to low-grade systemic inflammation and an increased risk of asthma exacerbations. Allergic rhinitis, atopic dermatitis, food allergies, and chronic urticaria also seem to be related to this state of chronic low-grade systemic inflammation typical of obese children. Vitamin D deficiency appears to play a role in allergic rhinitis, while dyslipidemia and skin barrier defects could explain the link between obesity and atopic dermatitis. Starting from this evidence, it becomes of fundamental importance to act on body weight control to achieve general and allergic health, disentangling the detrimental link between obesity allergic diseases and childhood obesity. Further studies on the association between adiposity and atopy are needed, confirming the biologically active role of fat tissue in the development of allergic diseases and exploring the possibility of new therapeutic strategies.

Predictive Power of Oxygen Desaturation Index (ODI) and Apnea-Hypopnea Index (AHI) in Detecting Long-Term Neurocognitive and Psychosocial Outcomes of Sleep-Disordered Breathing in Children: A Questionnaire-Based Study.

Pediatric obstructive sleep apnea can negatively affect children's neurocognitive function and development, hindering academic and adaptive goals. Questionnaires are suitable for assessing neuropsychological symptoms in children with sleep-disordered breathing. The study aimed to evaluate the effectiveness of using the Oxygen Desaturation Index compared to the Obstructive Apnea-Hypopnea Index in predicting long-term consequences of sleep-disordered breathing in children. We conducted a retrospective analysis of respiratory polysomnography recordings from preschool and school-age children (mean age: 5.8 ± 2.8 years) and followed them up after an average of 3.1 ± 0.8 years from the home-based polysomnography. We administered three validated questionnaires to the parents/caregivers of the children by phone. Our results showed that children with an Oxygen Desaturation Index (ODI) greater than one event per hour exhibited symptoms in four domains (physical, school-related, Quality of Life [QoL], and attention deficit hyperactivity disorder [ADHD]) at follow-up, compared to only two symptoms (physical and school-related) found in children with an Obstructive Apnea-Hypopnea Index greater than one event per hour at the time of diagnosis. Our study also found a significant correlation between the minimum SpO2 (%) recorded at diagnosis and several outcomes, including Pediatric Sleep Questionnaire (PSQ) scores, physical, social, and school-related outcomes, and ADHD index at follow-up. These results suggest that the Oxygen Desaturation Index could serve as a valuable predictor of long-term symptoms in children with sleep-disordered breathing, which could inform treatment decisions. Additionally, measuring minimum SpO2 levels may help assess the risk of developing long-term symptoms and monitor treatment outcomes.

Metabolomic Studies in Inborn Errors of Metabolism: Last Years and Future Perspectives.

The inborn errors of metabolism (IEMs or Inherited Metabolic Disorders) are a heterogeneous group of diseases caused by a deficit of some specific metabolic pathways. IEMs may present with multiple overlapping symptoms, sometimes difficult delayed diagnosis and postponed therapies. Additionally, many IEMs are not covered in newborn screening and the diagnostic profiling in the metabolic laboratory is indispensable to reach a correct diagnosis. In recent years, Metabolomics helped to obtain a better understanding of pathogenesis and pathophysiology of IEMs, by validating diagnostic biomarkers, discovering new specific metabolic patterns and new IEMs itself. The expansion of Metabolomics in clinical biochemistry and laboratory medicine has brought these approaches in clinical practice as part of newborn screenings, as an exam for differential diagnosis between IEMs, and evaluation of metabolites in follow up as markers of severity or therapies efficacy. Lastly, several research groups are trying to profile metabolomics data in platforms to have a holistic vision of the metabolic, proteomic and genomic pathways of every single patient. In 2018 this team has made a review of literature to understand the value of Metabolomics in IEMs. Our review offers an update on use and perspectives of metabolomics in IEMs, with an overview of the studies available from 2018 to 2022.

Current factor IX replacement options for hemophilia B and the challenges ahead.

INTRODUCTION: Therapy for hemophilia B is aimed at replacing the congenital deficiency of coagulation factor IX (FIX). For replacement therapy, several FIX concentrates derived from donated human plasma or engineered by recombinant DNA technology are currently commercially available. The use of these products is well established and permit patients a relatively normal life. To further improve treatment efficacy, recombinant FIX products with a prolonged half-life have been developed, allowing relaxed prophylactic dosing and reducing treatment burden. AREAS COVERED: In this review, we explore the current FIX replacement options for hemophilia B patients by analyzing the outcomes of their main clinical trials. We cover advances in the FIX molecules with extended half-life (EHL). Published literature on products for replacement of hemophilia B was retrieved using PubMed with no temporal limits. EXPERT OPINION: The recent introduction of recombinant EHL FIX products has represented a major advance in the therapeutic management of hemophilia B patients, permitting both a reduction of treatment burden and improving patients' compliance to prophylaxis and, ultimately, quality of life.

Relationships between 25-Hydroxyvitamin D Levels and Obstructive Sleep Apnea Severity in Children: An Observational Study.

The prevalence of hypovitaminosis D is increasing worldwide. Vitamin D deficiency is supposed to play a role in sleep disturbances, but the complex relationships between hypovitaminosis D and pediatric obstructive sleep apnea syndrome (OSAS) are still incompletely understood. This study was aimed to retrospectively investigate the vitamin D status and significant clinical, laboratory, and instrumental variables in a cohort of pediatric patients with OSAS and to assess the possible relationship between serum vitamin D levels and OSAS severity. We consecutively enrolled all children aged 2-14 years admitted to our Pediatric Clinic from 1 July 2018 to 30 November 2020 for sleep-disordered breathing. Each patient underwent standard overnight in-hospital polygraphic evaluation, measurement of serum 25-hydroxyvitamin D (25(OH)D) levels, and clinical and laboratory investigation. A total of 127 children with OSAS were included. The 25(OH)D levels and BMI of OSAS patients were compared with those of an age-matched control group: the serum 25(OH)D levels were significantly lower in OSAS patients than in controls (22.4 vs. 25.5 ng/mL; p-value = 0.009), whereas no differences in the BMI percentile were found between the two groups. The mean value of 25(OH)D was not significantly lower (20.9 ng/mL) in the severe OSAS group compared with the mild (23.0 ng/mL) and moderate (23.3 ng/mL) OSAS groups (p-value = 0.28). Our findings indicate a relationship between vitamin D status and OSAS in children and suggest that severe cases of OSAS have lower vitamin D levels. Future, more extensive prospective studies are needed to confirm such preliminary findings.