Diagnosis and Management of Pediatric Diseases

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (15 August 2019) | Viewed by 72453

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Guest Editor
Department of Laboratory Medicine & Pathology, Division of Anatomical Pathology, Children’s Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON K1H 8L1, Canada
Interests: gastrointestinal/biliary diseases; metabolic diseases; congenital heart disease; mitochondrial DNA-related cardiomyopathies; carcinogenesis (bone/liver)
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Dear Colleagues,

The recent progress identified in Neonatal and Pediatric Intensive Care of the last 20 years is astonishing. The possibility of survival of premature babies and newborns with very low weight has increased exponentially. However, the pulmonary and gastrointestinal functions, as well as the immune systems, remain critical. There is an increased rate of infection at this age, and sepsis and cardiovascular function are intimately related and therapy. The procedures of diagnosis in the neonatal settings are overlapping with diagnostic algorithms used at older age, but in any situation, they remain a complex and dynamic process, which requires an accurate medical history, a skilful physical examination, appropriate laboratory tests, and imaging studies with or without anatomo-pathological examination of tissue biopsies. However, even with these tactics and steps forward, clinical diagnosis may frequently remain elusive. It may be a quite long journey from the first appearance of symptom or sign to the final diagnosis. To the physician the impression is that new techniques seem to shorten this journey swiftly. Among the most promising techniques, the next-generation sequencing (NGS) may play a major role in this decade. NGS is becoming more and more used in clinics other than in academia, although one of the most challenging aspects of NGS testing may reside in its analytical validity. The field of metabolomics is indeed almost lightfast developing, particularly in paediatrics. Liquid chromatography mass spectrometry (LC-MS) with nanoflow pre-concentration (nLC−MS) is currently more often used in the proteomic field to investigate minor amounts of both proteins and peptide samples. In metabolomics, just very recently, nLC-MS is becoming to be more accepted completing other advanced lab technologies. This approach is tightly allied with the concept of personalized healthcare and patient management. Over the last few years, it seems that a range of robust assays supporting the pre-clinical detection of pathologies are being established. In clouds and electronic libraries, new biomarkers are being identified for several pathologies in paediatrics. Management of paediatric diseases may become extenuating and the use of single nucleotide polymorphisms for the treatment of some paediatric conditions has been proposed. Paediatric trial networks provide paediatricians, researchers, and agencies with new information on how children may respond to drugs and medications. Off-patent drugs that are lacking data on safety, efficacy, and dosing in the paediatric population may be used and their primary goal is to generate the data showing potential health benefits and findings necessary to produce evidence-based medicine for future guidelines in the clinical practice. The present Special Issue aims at bringing a collection of wet lab research and review articles together to summarize a state of the art, problems and future directions in the diagnosis and management of paediatric diseases and I look forward to peruse your contributions.

Prof. Dr. Consolato Maria Sergi
Guest Editor

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Keywords

  • newborn, child
  • diagnosis
  • biomarkers
  • imaging
  • biopsy
  • histology
  • mass spectrometry
  • therapy
  • management
  • clinical trials

Published Papers (12 papers)

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Editorial

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5 pages, 190 KiB  
Editorial
Pediatrics: An Evolving Concept for the 21st Century
by Consolato M. Sergi
Diagnostics 2019, 9(4), 201; https://doi.org/10.3390/diagnostics9040201 - 25 Nov 2019
Cited by 3 | Viewed by 2054
Abstract
Pediatrics is rapidly evolving, and the diagnostic tools are expanding the spectrum of diagnoses that can be identified at the bedside [...] Full article
(This article belongs to the Special Issue Diagnosis and Management of Pediatric Diseases)

Research

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8 pages, 758 KiB  
Article
Preterm Perinatal Hypoxia-Ischemia Does not Affect Somatosensory Evoked Potentials in Adult Rats
by Melinda Barkhuizen, Johan S.H. Vles, Ralph van Mechelen, Marijne Vermeer, Boris W. Kramer, Peter Chedraui, Paul Bergs, Vivianne H.J.M. van Kranen-Mastenbroek and Antonio W.D. Gavilanes
Diagnostics 2019, 9(3), 123; https://doi.org/10.3390/diagnostics9030123 - 18 Sep 2019
Cited by 2 | Viewed by 3397
Abstract
Somatosensory evoked potentials (SSEPs) are a valuable tool to assess functional integrity of the somatosensory pathways and for the prediction of sensorimotor outcome in perinatal injuries, such as perinatal hypoxia-ischemia (HI). In the present research, we studied the translational potential of SSEPs together [...] Read more.
Somatosensory evoked potentials (SSEPs) are a valuable tool to assess functional integrity of the somatosensory pathways and for the prediction of sensorimotor outcome in perinatal injuries, such as perinatal hypoxia-ischemia (HI). In the present research, we studied the translational potential of SSEPs together with sensory function in the male adult rat with perinatal HI compared to the male healthy adult rat. Both somatosensory response and evoked potential were measured at 10-11 months after global perinatal HI. Clear evoked potentials were obtained, but there were no group differences in the amplitude or latency of the evoked potentials of the preceding sensory response. The bilateral tactile stimulation test was also normal in both groups. This lack of effect may be ascribed to the late age-of-testing and functional recovery of the rats. Full article
(This article belongs to the Special Issue Diagnosis and Management of Pediatric Diseases)
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11 pages, 1415 KiB  
Article
Glutathione Blood Concentrations: A Biomarker of Oxidative Damage Protection during Cardiopulmonary Bypass in Children
by Angela Satriano, Simone Franchini, Giuseppe Lapergola, Francesca Pluchinotta, Luigi Anastasia, Ekaterina Baryshnikova, Giovanni Livolti and Diego Gazzolo
Diagnostics 2019, 9(3), 118; https://doi.org/10.3390/diagnostics9030118 - 13 Sep 2019
Cited by 6 | Viewed by 2538
Abstract
Background. Pediatric open-heart surgery with cardiopulmonary bypass (CPB) still remains a risky interventional procedure at high mortality/morbidity. To date, there are no clinical, laboratory, and/or monitoring parameters providing useful information on perioperative stress. We therefore investigated whether blood concentrations of glutathione (GSH), a [...] Read more.
Background. Pediatric open-heart surgery with cardiopulmonary bypass (CPB) still remains a risky interventional procedure at high mortality/morbidity. To date, there are no clinical, laboratory, and/or monitoring parameters providing useful information on perioperative stress. We therefore investigated whether blood concentrations of glutathione (GSH), a powerful endogenous antioxidant, changed in the perioperative period. Methods. We conducted an observational study in 35 congenital heart disease (CHD) children in whom perioperative standard laboratory and monitoring parameters and GSH blood levels were assessed at five monitoring time points. Results. GSH showed a pattern characterized by a progressive increase from pre-surgery up to 24 h after surgery, reaching its highest peak at the end of CPB. GSH measured at the end of CPB correlated with CPB duration, cross-clamping, arterial oxygen partial pressure, and with body core temperature. Conclusions. The increase in GSH levels in the perioperative period suggests a compensatory mechanism to oxidative damage during surgical procedure. Caution is needed in controlling different CPB phases, especially systemic reoxygenation in a population that is per se more prone to oxidative stress/damage. The findings may point the way to detecting the optimal temperature and oxygenation target by biomarker monitoring. Full article
(This article belongs to the Special Issue Diagnosis and Management of Pediatric Diseases)
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14 pages, 1728 KiB  
Article
An Easy and Reliable Strategy for Making Type I Interferon Signature Analysis Comparable among Research Centers
by Alessia Pin, Lorenzo Monasta, Andrea Taddio, Elisa Piscianz, Alberto Tommasini and Alessandra Tesser
Diagnostics 2019, 9(3), 113; https://doi.org/10.3390/diagnostics9030113 - 04 Sep 2019
Cited by 16 | Viewed by 3060
Abstract
Interferon-stimulated genes (ISGs) are a set of genes whose transcription is induced by interferon (IFN). The measure of the expression of ISGs enables calculating an IFN score, which gives an indirect estimate of the exposition of cells to IFN-mediated inflammation. The measure of [...] Read more.
Interferon-stimulated genes (ISGs) are a set of genes whose transcription is induced by interferon (IFN). The measure of the expression of ISGs enables calculating an IFN score, which gives an indirect estimate of the exposition of cells to IFN-mediated inflammation. The measure of the IFN score is proposed for the screening of monogenic interferonopathies, like the Aicardi-Goutières syndrome, or to stratify subjects with systemic lupus erythematosus to receive IFN-targeted treatments. Apart from these scenarios, there is no agreement on the diagnostic value of the score in distinguishing IFN-related disorders from diseases dominated by other types of cytokines. Since the IFN score is currently measured in several research hospitals, merging experiences could help define the potential of scoring IFN inflammation in clinical practice. However, the IFN score calculated at different laboratories may be hardly comparable due to the distinct sets of IFN-stimulated genes assessed and to different controls used for data normalization. We developed a reliable approach to minimize the inter-laboratory variability, thereby providing shared strategies for the IFN signature analysis and allowing different centers to compare data and merge their experiences. Full article
(This article belongs to the Special Issue Diagnosis and Management of Pediatric Diseases)
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9 pages, 792 KiB  
Article
The HD-OCT Study May Be Useful in Searching for Markers of Preclinical Stage of Diabetic Retinopathy in Patients with Type 1 Diabetes
by Magdalena Kołodziej, Arleta Waszczykowska, Irmina Korzeniewska-Dyl, Aleksandra Pyziak-Skupien, Konrad Walczak, Dariusz Moczulski, Piotr Jurowski, Wojciech Młynarski, Agnieszka Szadkowska and Agnieszka Zmysłowska
Diagnostics 2019, 9(3), 105; https://doi.org/10.3390/diagnostics9030105 - 26 Aug 2019
Cited by 9 | Viewed by 3549
Abstract
The aim of the study was to analyze the thickness of individual retinal layers in patients with type 1 diabetes (T1D) in comparison to the control group and in relation to markers of diabetes metabolic control. The study group consisted of 111 patients [...] Read more.
The aim of the study was to analyze the thickness of individual retinal layers in patients with type 1 diabetes (T1D) in comparison to the control group and in relation to markers of diabetes metabolic control. The study group consisted of 111 patients with an average of 6-years of T1D duration. The control group included 36 gender- and age-matched individuals. In all patients optical coherence tomography (OCT) study was performed using HD-OCT Cirrus 5000 with evaluation of optic nerve head (ONH) parameters, thickness of retinal nerve fiber layer (RNFL) with its quadrants, macular full-thickness parameters, ganglion cells with inner plexus layer (GCIPL) and choroidal thickness (CT). Lower disc area value was observed in the study group as compared to controls (p = 0.0215). Negative correlations were found both between age at examination and rim area (R = −0.28, p = 0.0007) and between superior RNFL thickness and duration of diabetes (R = −0.20, p = 0.0336). Positive correlation between center thickness and SD for average glycemia (R = 0.30, p = 0.0071) was noted. Temporal CT correlated positively with age at examination (R = 0.21, p = 0.0127). The selected parameters the HD-OCT study may in the future serve as potential markers of preclinical phase of DR in patients with T1D. Full article
(This article belongs to the Special Issue Diagnosis and Management of Pediatric Diseases)
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15 pages, 2274 KiB  
Article
Left Ventricular Dysfunction and Plasmatic NT-proBNP Are Associated with Adverse Evolution in Respiratory Syncytial Virus Bronchiolitis
by Moises Rodriguez-Gonzalez, Alvaro Antonio Perez-Reviriego, Ana Castellano-Martinez, Simon Lubian-Lopez and Isabel Benavente-Fernandez
Diagnostics 2019, 9(3), 85; https://doi.org/10.3390/diagnostics9030085 - 27 Jul 2019
Cited by 15 | Viewed by 3238
Abstract
Aim: To investigate whether the presence of left ventricular myocardial dysfunction (LVMD) assessed by Tei index (LVTX) impacts the outcomes of healthy infants with Respiratory Syncytial Virus Bronchiolitis (RSVB). To explore whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) increases the accuracy of traditional clinical [...] Read more.
Aim: To investigate whether the presence of left ventricular myocardial dysfunction (LVMD) assessed by Tei index (LVTX) impacts the outcomes of healthy infants with Respiratory Syncytial Virus Bronchiolitis (RSVB). To explore whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) increases the accuracy of traditional clinical markers in predicting the outcomes. Methods: A single-centre, prospective, cohort study including healthy infants aged 1–12 months old admitted for RSVB between 1 October 2016 and 1 April 2017. All patients underwent clinical, laboratory and echocardiographic evaluation within 24 h of admission. Paediatric intensive care unit (PICU) admission was defined as severe disease. Results: We enrolled 50 cases of RSVB (median age of 2 (1–6.5) months; 40% female) and 50 age-matched controls. We observed higher values of LVTX in infants with RSVB than in controls (0.42 vs. 0.36; p = 0.008). Up to nine (18%) children presented with LVMD (LVTX > 0.5), with a higher incidence of PICU admission (89% vs. 5%; p < 0.001). The diagnostic performance of NT-proBNP in predicting LVMD was high (area under the receiver operator characteristic curve (AUC) 0.95, CI 95% 0.90–1). The diagnostic yield of the predictive model for PICU admission that included NT-proBNP was excellent (AUC 0.945, CI 95% 0.880–1), and significantly higher than the model without NT-proBNP (p = 0.026). Conclusions: LVMD could be present in healthy infants with RSVB who develop severe disease. NT-proBNP seems to improve traditional clinical markers for outcomes. Full article
(This article belongs to the Special Issue Diagnosis and Management of Pediatric Diseases)
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Review

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13 pages, 6067 KiB  
Review
Pediatric Sarcoidosis: A Review with Emphasis on Early Onset and High-Risk Sarcoidosis and Diagnostic Challenges
by Brian Chiu, Jackie Chan, Sumit Das, Zainab Alshamma and Consolato Sergi
Diagnostics 2019, 9(4), 160; https://doi.org/10.3390/diagnostics9040160 - 25 Oct 2019
Cited by 26 | Viewed by 6566
Abstract
Sarcoidosis is a non-necrotizing granulomatous inflammatory syndrome with multisystemic manifestations. We performed a systematic review of sarcoidosis in the pediatric population with particular emphases on early onset sarcoidosis, high-risk sarcoidosis, and newly reported or unusual sarcoid-related diseases. Blau Syndrome and early onset sarcoidosis/ [...] Read more.
Sarcoidosis is a non-necrotizing granulomatous inflammatory syndrome with multisystemic manifestations. We performed a systematic review of sarcoidosis in the pediatric population with particular emphases on early onset sarcoidosis, high-risk sarcoidosis, and newly reported or unusual sarcoid-related diseases. Blau Syndrome and early onset sarcoidosis/ BS-EOS are seen in children younger than five years old presenting with extra-thoracic manifestations but usually without lymphadenopathy and/or pulmonary involvement. The prevalence of high-risk sarcoidosis is very low in children and is further limited by the difficulty of diagnosis in symptomatic children and underdiagnosis in subclinical or asymptomatic patients. Reports of sarcoidal syndromes in users of E-cigarette/marijuana/other flavorings and their induction in cancer immunotherapies are of interests and may be challenging to differentiate from metastatic malignancy. The diagnostic considerations in pediatric sarcoidosis are to support a compatible clinicoradiographic presentation and the pathologic findings of non-necrotizing granulomas by ruling out granulomas of infective etiology. There is no absolutely reliable diagnostic test for sarcoidosis at present. The use of endoscopic bronchial ultrasound (EBUS) and transbronchial fine needle aspiration (TBNA) sampling of intrathoracic lymph nodes and lung, and for superficially accessible lesions, with cytopathological assessment and pathological confirmations provide fair diagnostic yield and excellent patient safety profile in children. Full article
(This article belongs to the Special Issue Diagnosis and Management of Pediatric Diseases)
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16 pages, 239 KiB  
Review
Current Diabetes Technology: Striving for the Artificial Pancreas
by Natalie Allen and Anshu Gupta
Diagnostics 2019, 9(1), 31; https://doi.org/10.3390/diagnostics9010031 - 15 Mar 2019
Cited by 42 | Viewed by 9364
Abstract
Diabetes technology has continually evolved over the years to improve quality of life and ease of care for affected patients. Frequent blood glucose (BG) checks and multiple daily insulin injections have become standard of care in Type 1 diabetes (T1DM) management. Continuous glucose [...] Read more.
Diabetes technology has continually evolved over the years to improve quality of life and ease of care for affected patients. Frequent blood glucose (BG) checks and multiple daily insulin injections have become standard of care in Type 1 diabetes (T1DM) management. Continuous glucose monitors (CGM) allow patients to observe and discern trends in their glycemic control. These devices improve quality of life for parents and caregivers with preset alerts for hypoglycemia. Insulin pumps have continued to improve and innovate since their emergence into the market. Hybrid closed-loop systems have harnessed the data gathered with CGM use to aid in basal insulin dosing and hypoglycemia prevention. As technology continues to progress, patients will likely have to enter less and less information into their pump system manually. In the future, we will likely see a system that requires no manual patient input and allows users to eat throughout the day without counting carbohydrates or entering in any blood sugars. As technology continues to advance, endocrinologists and diabetes providers need to stay current to better guide their patients in optimal use of emerging management tools. Full article
(This article belongs to the Special Issue Diagnosis and Management of Pediatric Diseases)
12 pages, 2074 KiB  
Review
Clinicopathological Spectrum of Bilirubin Encephalopathy/Kernicterus
by Sumit Das and Frank K.H. van Landeghem
Diagnostics 2019, 9(1), 24; https://doi.org/10.3390/diagnostics9010024 - 28 Feb 2019
Cited by 34 | Viewed by 11158
Abstract
Bilirubin encephalopathy/kernicterus is relatively rare, but continues to occur despite universal newborn screening. What is more interesting is the spectrum of clinical and even neuropathological findings that have been reported in the literature to be associated with bilirubin encephalopathy and kernicterus. In this [...] Read more.
Bilirubin encephalopathy/kernicterus is relatively rare, but continues to occur despite universal newborn screening. What is more interesting is the spectrum of clinical and even neuropathological findings that have been reported in the literature to be associated with bilirubin encephalopathy and kernicterus. In this review, the authors discuss the array of clinicopathological findings reported in the context of bilirubin encephalopathy and kernicterus, as well as the types of diagnostic testing used in patients suspected of having bilirubin encephalopathy or kernicterus. The authors aim to raise the awareness of these features among both pediatric neurologists and neuropathologists. Full article
(This article belongs to the Special Issue Diagnosis and Management of Pediatric Diseases)
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16 pages, 1140 KiB  
Review
Sialidosis: A Review of Morphology and Molecular Biology of a Rare Pediatric Disorder
by Aiza Khan and Consolato Sergi
Diagnostics 2018, 8(2), 29; https://doi.org/10.3390/diagnostics8020029 - 25 Apr 2018
Cited by 43 | Viewed by 9405
Abstract
Sialidosis (MIM 256550) is a rare, autosomal recessive inherited disorder, caused by α-N-acetyl neuraminidase deficiency resulting from a mutation in the neuraminidase gene (NEU1), located on 6p21.33. This genetic alteration leads to abnormal intracellular accumulation as well as urinary [...] Read more.
Sialidosis (MIM 256550) is a rare, autosomal recessive inherited disorder, caused by α-N-acetyl neuraminidase deficiency resulting from a mutation in the neuraminidase gene (NEU1), located on 6p21.33. This genetic alteration leads to abnormal intracellular accumulation as well as urinary excretion of sialyloligosaccharides. A definitive diagnosis is made after the identification of a mutation in the NEU1 gene. So far, 40 mutations of NEU1 have been reported. An association exists between the impact of the individual mutations and the severity of clinical presentation of sialidosis. According to the clinical symptoms, sialidosis has been divided into two subtypes with different ages of onset and severity, including sialidosis type I (normomorphic or mild form) and sialidosis type II (dysmorphic or severe form). Sialidosis II is further subdivided into (i) congenital; (ii) infantile; and (iii) juvenile. Despite being uncommon, sialidosis has enormous clinical relevance due to its debilitating character. A complete understanding of the underlying pathology remains a challenge, which in turn limits the development of effective therapeutic strategies. Furthermore, in the last few years, some atypical cases of sialidosis have been reported as well. We herein attempt to combine and discuss the underlying molecular biology, the clinical features, and the morphological patterns of sialidosis type I and II. Full article
(This article belongs to the Special Issue Diagnosis and Management of Pediatric Diseases)
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11 pages, 1293 KiB  
Review
Fine Needle Aspiration Cytology for Neck Masses in Childhood. An Illustrative Approach
by Consolato Sergi, Aneesh Dhiman and Jo-Ann Gray
Diagnostics 2018, 8(2), 28; https://doi.org/10.3390/diagnostics8020028 - 22 Apr 2018
Cited by 12 | Viewed by 11852
Abstract
The primary indication of fine-needle aspiration cytology of the head and neck region is a thyroid nodule or a mass located in the cervical area or the head. Although a thyroid nodule may raise the suspicion of malignancy, less than one in 20 [...] Read more.
The primary indication of fine-needle aspiration cytology of the head and neck region is a thyroid nodule or a mass located in the cervical area or the head. Although a thyroid nodule may raise the suspicion of malignancy, less than one in 20 cases results in a carcinoma. In addition, the list of differential diagnoses is quite different according to the age of the patient. A number of benign lesions, such as branchial cysts, sialadenosis, and sialoadenitis are often seen in childhood and youth. The malignant lesions that are on the top of the list of a pediatric mass of the head and neck (H&N) region include rhabdomyosarcoma, neuroblastoma, and papillary carcinoma of the thyroid gland. This critical review of the diagnostic features of a pediatric mass of the H&N region is accompanied by panels of several cytology features that may be of help to the cytopathologist and clinician. Full article
(This article belongs to the Special Issue Diagnosis and Management of Pediatric Diseases)
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Other

6 pages, 616 KiB  
Case Report
Subcutaneous and Mediastinal Emphysema Followed by Group A Beta-Hemolytic Streptococci Mediastinitis. A Complicated Course after Adenotonsillectomy: Case Report
by Anne Duvekot, Gwen van Heesch and Laura Veder
Diagnostics 2019, 9(1), 11; https://doi.org/10.3390/diagnostics9010011 - 15 Jan 2019
Cited by 5 | Viewed by 4833
Abstract
Tonsillectomy is a commonly performed surgery in the daily practice of an otorhinolaryngologist. For patients as well as health professionals, the best known complication is post-operative bleeding. Among the less noted, but potentially life-threatening, complications are the development of subcutaneous emphysema and the [...] Read more.
Tonsillectomy is a commonly performed surgery in the daily practice of an otorhinolaryngologist. For patients as well as health professionals, the best known complication is post-operative bleeding. Among the less noted, but potentially life-threatening, complications are the development of subcutaneous emphysema and the presence of bacteremia due to group A hemolytic streptococci. In this report, we describe a severely complicated clinical course after an uncomplicated adenotonsillectomy in a young boy. Increased awareness of relatively unknown complications after adenotonsillectomy amongst surgeons, pediatricians and anesthesiologists is desirable to facilitate rapid diagnosis and adequate treatment in order to prevent life-threatening situations. Full article
(This article belongs to the Special Issue Diagnosis and Management of Pediatric Diseases)
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