Impact of COVID-19 on Pediatric Inflammatory Bowel Diseases-From Expectations to Reality.

Viral infections have always been considered a threat to global health, with numerous outbreaks across time. Despite the relative recent experience with coronavirus-associated diseases such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), severe acute respiratory syndrome-2's (SARS-CoV-2) continuous evolution displays a different behavior. With a tropism for both respiratory and digestive mucosa, coronavirus disease 2019 (COVID-19) and inflammatory bowel disease (IBD) seem to share a particular common background. Current literature offers evidence that viral alteration of the immune system, inflammatory intestinal tissue damage, increased intestinal permeability, incomplete viral clearance with viral antigen persistence, and intestinal dysbiosis, might explain SARS-CoV-2-IBD relationship in terms of etiopathogenesis and evolution. The hyperinflammatory state that both entities have in common explains the lack of success of current IBD therapy, raising the need for new personalized therapeutic options, with better outcomes for IBD and COVID-19 as well. This review aims to summarize the current available data on pediatric IBD evolution, management, and outcomes in the post-COVID period, with an emphasis on the particular aspects of the SARS-CoV-2-IBD relationship in children.

Nanotechnology Innovations in Pediatric Cardiology and Cardiovascular Medicine: A Comprehensive Review.

(1) Background: Nanomedicine, incorporating various nanoparticles and nanomaterials, offers significant potential in medical practice. Its clinical adoption, however, faces challenges like safety concerns, regulatory hurdles, and biocompatibility issues. Despite these, recent advancements have led to the approval of many nanotechnology-based products, including those for pediatric use. (2) Methods: Our approach included reviewing clinical, preclinical, and animal studies, as well as literature reviews from the past two decades and ongoing trials. (3) Results: Nanotechnology has introduced innovative solutions in cardiovascular care, particularly in managing myocardial ischemia. Key developments include drug-eluting stents, nitric oxide-releasing coatings, and the use of magnetic nanoparticles in cardiomyocyte transplantation. These advancements are pivotal for early detection and treatment. In cardiovascular imaging, nanotechnology enables noninvasive assessments. In pediatric cardiology, it holds promise in assisting the development of biological conduits, synthetic valves, and bioartificial grafts for congenital heart defects, and offers new treatments for conditions like dilated cardiomyopathy and pulmonary hypertension. (4) Conclusions: Nanomedicine presents groundbreaking solutions for cardiovascular diseases in both adults and children. It has the potential to transform cardiac care, from enhancing myocardial ischemia treatment and imaging techniques to addressing congenital heart issues. Further research and guideline development are crucial for optimizing its clinical application and revolutionizing patient care.

Statins-Beyond Their Use in Hypercholesterolemia: Focus on the Pediatric Population.

Statins are a class of medications primarily used in adults to lower cholesterol levels and reduce the risk of cardiovascular events. However, the use of statins in children is generally limited and carefully considered despite the well-documented anti-inflammatory, anti-angiogenic, and pro-apoptotic effects, as well as their effect on cell signaling pathways. These multifaceted effects, known as pleiotropic effects, encompass enhancements in endothelial function, a significant reduction in oxidative stress, the stabilization of atherosclerotic plaques, immunomodulation, the inhibition of vascular smooth muscle proliferation, an influence on bone metabolism, anti-inflammatory properties, antithrombotic effects, and a diminished risk of dementia. In children, recent research revealed promising perspectives on the use of statins in various conditions including neurological, cardiovascular, and oncologic diseases, as well as special situations, such as transplanted children. The long-term safety and efficacy of statins in children are still subjects of ongoing research, and healthcare providers carefully assess the individual risk factors and benefits before prescribing these medications to pediatric patients. The use of statins in children is generally less common than in adults, and it requires close monitoring and supervision by healthcare professionals. Further research is needed to fully assess the pleiotropic effects of statins in the pediatric population.

Arrhythmogenic Right Ventricular Cardiomyopathy in Children: A Systematic Review.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disease characterized by the progressive replacement of the normal myocardium by fibroadipocytic tissue. The importance of an early diagnosis is supported by a higher risk of sudden cardiac death in the pediatric population. We reviewed the literature on diagnosis, risk stratification, and prognosis in the pediatric population with ARVC. In case reports which analyzed children with ARVC, the most common sign was ventricular tachycardia, frequently presenting as dizziness, syncope, or even cardiac arrest. Currently, there is no gold standard for diagnosing ARVC in children. Nevertheless, genetic analysis may provide a proper diagnosis tool for asymptomatic cases. Although risk stratification is recommended in patients with ARVC, a validated prediction model for risk stratification in children is still lacking; thus, it is a matter of further research. In consequence, even though ARVC is a relatively rare condition in children, it negatively impacts the survival and clinical outcomes of the patients. Therefore, appropriate and validated diagnostic and risk stratification tools are crucial for the early detection of children with ARVC, ensuring a prompt therapeutic intervention.

New Insights into the Role of INSL-3 in the Development of Cryptorchidism.

Cryptorchidism, defined as the failure of at least one or both testicles to descend into the scrotal pouches, is the most frequent (1.6-9% at birth, 1/20 males at birth) congenital anomaly encountered in newborn males, resulting in one of the most frequent causes of non-obstructive azoospermia in men. Similar to other congenital malformations, cryptorchidism is thought to be caused by endocrine and genetic factors, combined with maternal and environmental influences. The etiology of cryptorchidism is unknown, as it involves complex mechanisms aiming to control the testicular development and descent from their initial intra-abdominal location in scrotal pouches. The implication of insulin-like 3 (INSL-3) associated with its receptor (LGR8) is critical. Genetic analysis discloses functionally deleterious mutations in INSL3 and GREAT/LGR8 genes. In this literature review, we discuss and analyze the implication of INSL3 and the INSL3/LGR8 mutation in the occurrence of cryptorchidism in both human and animal models.

The Role of Urinary NGAL in the Management of Primary Vesicoureteral Reflux in Children.

Vesicoureteral reflux (VUR) is the most frequent congenital urinary tract malformation and an important risk factor for urinary tract infections (UTIs). Up to 50% of children with VUR may develop reflux nephropathy (RN), and the diagnosis and monitoring of renal scars are invasive and costly procedures, so it is paramount to find a non-invasive and accurate method to predict the risk of renal damage. Neutrophil gelatinase-associated lipocalin (NGAL) has already proven to be a good predictive biomarker in acute kidney injuries, but there are few studies that have investigated the role of NGAL in primary VUR in children. Our aim is to review the predictive value of urine NGAL (uNGAL) as a non-invasive biomarker of RN in children with primary VUR, as well as its ability to predict the evolution of chronic kidney disease (CKD). Based on our analysis of the available original studies, uNGAL can be an accurate and reliable biomarker of RN and its progression to CKD. Some studies suggested a good correlation between VUR severity and uNGAL levels, but other studies found no significant correlation. The relationship between VUR severity and uNGAL levels is likely complex and influenced by factors such as UTIs, the timing of the urine sample collection, and the age and overall health of the patient.

Watchful Waiting in Pediatric Acute Otitis Media: A Real Practice Approach or an Intangible Desideratum?

Acute otitis media (AOM) in children is one of the leading causes of health care visits and antibiotic prescriptions worldwide. The overall aim of the current study is twofold: 1. to analyze and discuss the antibiotic prescription patterns in AOM in children without complications or risk factors and 2. to assess to what extent the watchful-waiting approach is a real practice or a mere desideratum. We performed an electronic search in the PubMed and Embase databases from 2013 to 2023 to capture original research studies investigating antibiotic prescribing patterns for AOM in children. Among the 12 papers included in the analysis, the antibiotic prescription rate ranged from 44.8% to 98%. Our study reveals similarities regarding the use of amoxicillin as a first-line antibiotic in pediatric AOM, but also discrepancies in the watchful-waiting approach attitude and in the choice of second or third-line antimicrobial agents. The proportion of cases managed with the watchful-waiting approach ranged from 7.5% (Australia) to 55.2% (Finland). Denmark was the only country reporting penicillin V as a first-choice regimen for children with AOM, which fulfils the guidelines' recommendations. The most unsatisfying rate of amoxicillin use was recorded in Japan, contrary to the recommendations of local guidelines. The use of quinolones was reported in two out of twelve studies, with the highest proportion in Japan, where tosufloxacin was used in 21.4% of the total number of cases. The duration of the antibiotic regimens was analyzed in three out of twelve papers. Since global antibiotic overuse contributes to the emergence of antibiotic resistant bacteria, new strategies are needed to increase the rate of watchful waiting and to promote the judicious use of antibiotics.

Unusual Association of Diamond-Blackfan Anemia and Severe Sinus Bradycardia in a Six-Month-Old White Infant: A Case Report and Literature Review.

Diamond-Blackfan anemia is a rare (6-7 million live births), inherited condition manifesting as severe anemia due to the impaired bone marrow production of red blood cells. We present the unusual case of a six month old infant with a de novo mutation of the RPS19 gene causing Diamond-Blackfan anemia who additionally suffers from severe sinus bradycardia. The infant was diagnosed with this condition at the age of four months; at the age of 6 months, she presents with severe anemia causing hypoxia which, in turn, caused severe dyspnea and polypnea, which had mixed causes (hypoxic and infectious) as the child was febrile. After correction of the overlapping diarrhea, metabolic acidosis, and severe anemia (hemoglobin < 3 g/dL), she developed severe persistent sinus bradycardia immediately after mild sedation (before central venous catheter insertion), not attributable to any of the more frequent causes, with a heart rate as low as 49 beats/min on 24 h Holter monitoring, less than the first percentile for age, but with a regular QT interval and no arrhythmia. The echocardiogram was unremarkable, showing a small interatrial communication (patent foramen ovale with left-to-right shunting), mild left ventricular hypertrophy, normal systolic and diastolic function, and mild tricuspid regurgitation. After red cell transfusion and appropriate antibiotic and supportive treatment, the child's general condition improved dramatically but the sinus bradycardia persisted. We consider this a case of well-tolerated sinus bradycardia and foresee a good cardiologic prognosis, while the hematologic prognosis remains determined by future corticoid response, treatment-related complications and risk of leukemia.

Acute Otitis Media in Children-Challenges of Antibiotic Resistance in the Post-Vaccination Era.

Acute otitis media (AOM) is a leading cause of antibiotic prescriptions in children worldwide, even in the era of pneumococcal conjugate vaccines. We aimed to assess the bacterial spectrum of AOM in children and to investigate the antimicrobial resistance profile in culture-positive cases. We performed a retrospective, tympanocentesis-based analysis of antimicrobial resistance patterns in children with AOM hospitalized in "St Mary" Emergency Hospital for Children Iasi, Romania, between January 2013 and December 2021. A total of 147 samples have been assessed, 97 (65.98%) of which had positive cultures, with Streptococcus pneumoniae and Haemophilus influenzae as the most common microorganisms. A worrying proportion, 82.85% (58/70), of the Streptococcus pneumoniae strains were multidrug-resistant. The World Health Organization included Streptococcus pneumoniae and Haemophilus influenzae on the medium priority group due to penicillin non-susceptibility and ampicillin-resistant strains, respectively. Consequently, strategies to address the threats of antimicrobial resistance are needed to reduce the potential negative effects on hospitalization costs.

uNGAL Predictive Value for Serum Creatinine Decrease in Critically Ill Children.

Acute kidney injury (AKI) occurs frequently in critically ill children, having an incidence of up to 26.9% and is associated with high morbidity and mortality in pediatric intensive care units (PICU). Currently, the decrease in the glomerular filtration rate is calculated using the serum creatinine levels. Nevertheless, there may be a 48 h delay between the renal injury and measurable increase in creatinine. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) has been validated in relation to cardiopulmonary bypass in children, being able to detect AKI before the functional change proven by the rise in serum creatinine. Our aim was to study the utility of using uNGAL in the management of critical pediatric patients admitted to our hospital in a six month period, more specifically, its capacity to predict AKI development, alone and in the association with the renal angina index (RAI). Twenty-eight critically ill children aged from 1 day to 15 years have been included. We found that an increase in uNGAL in day 1 of admission in the PICU was significantly correlated with a decrease in creatinine clearance but not anymore in day 3. However, in our sample uNGAL did not show a significant predictability for AKI development nor the supplementary incorporation of RAI into the prediction model. Therefore, apart from cardiac surgery, the efficacy and utility or uNGAL in the management of critically ill children is still questionable. For the best prediction, we will need to incorporate not only the RAI or other PICU scores, but other biomarkers such as KIM-1, urinary cystatin, and IL 18 in larger samples.

The Use of Clinical Scores in the Management of Immune Thrombocytopenic Purpura in Children.

While the majority of children with recently diagnosed ITP have a benign, self-limiting condition, most often with a spontaneously recovery, 40% of children with ITP progress toward persistent ITP and 10-20% goes toward chronicity. Several clinical scores have been developed with the aim to perform a better monitoring outcome or to differentiate transient vs. persistent ITP (e.g., Donato score). Our paper aims to describe and to compare the most important scores used in the management of ITP in children: bleeding severity scores and chronicity prediction scores. These scores include a combination of different already known risk factors: age, gender, presence of a previous infections or vaccination, bleeding grade, type of onset, platelet count at diagnosis. The real utility of these scores has been a matter of debate and no consensus has been reached so far as to their necessity to be implemented as compulsory tool in the care of children with ITP.

Otitis Media and Obesity-An Unusual Relationship in Children.

Otitis media (OM) represents a public health matter, being the main cause of preventable hearing loss in pediatric patients. Besides well-established risk factors for developing OM, such as craniofacial abnormalities, prematurity, low birth weight, or tobacco exposure, there is evidence that obesity could be associated with a high incidence of OM. Our aim is to perform a literature review on the state of current published research on the relationship between OM and obesity and to discuss the interconnectivity between these two entities. We conducted an electronic search in PubMed and EMBASE databases. Out of 176 references, 15 articles were included in our study. Our findings suggest that obesity and overweight might be risk factors for developing OM, and vice versa. The main mechanisms for developing OM in obese patients include alteration in cytokine profile, increased gastroesophageal reflux, and/or fat accumulation. Conversely, ear infections exposure might increase the risk of obesity, mostly by taste changes through middle ear cavity inflammation.

From Evidence to Clinical Guidelines in Antibiotic Treatment in Acute Otitis Media in Children.

Acute otitis media (AOM) in children represents a public health concern, being one of the leading causes of health care visits and antibiotic prescriptions worldwide. The overall aim of this paper is to unravel the major current insights into the antibiotic treatment of AOM in children. Our approach is three-fold: 1. a preclinical evaluation of antibiotics in animal models of AOM stressing on the advantages of different species when testing for different schemes of antibiotics; 2. an overview on the new antimicrobial agents whose efficacy has been demonstrated in refractory cases of AOM in children; and 3. an analysis of the different guidelines stressing on the differences and similarities between the various schemes of antibiotic treatment. The preferred therapeutic agents remain amoxicillin and the amoxicillin-clavulanate combination for AOM caused by Streptococcus pneumoniae, whereas oral cephalosporin is preferred in AOM due to Moraxella catarrhalis and Haemophilus influenzae. As for the second and third line antimicrobial treatments, there is a wide variety of suggested antibiotic classes with variations in duration and posology. The decision to prescribe antimicrobial treatment as a first-line choice is based on the severity of the symptoms in 16 of the guidelines included in this review.