Pediatrics is rapidly evolving, and the diagnostic tools are expanding the spectrum
of diagnoses that can be identified at the bedside. The recent progress identified
in pediatrics of the last 20 years is astonishing and has consolidated the concept
that children are not “smaller adults” and indeed, perinatal and pediatric pathology
has become an independent subspecialty in pathology with impressive intersections
with fetal medicine, neonatology, and pediatrics. The neonatal intensive care unit
(NICU) as well as the pediatric intensive care unit (PICU) play a major role in modern
hospitals. These sections of the hospital provide sick newborns and children with
the highest level of medical care. Differently from the general medical floors, both
units allow intensive nursing care and continuous monitoring of vital parameters,
including heart rate, breathing, and blood pressure. The survival of premature babies
and small for date newborns has increased exponentially in the last few decades. On
the other hand, the immune system, as well as the pulmonary and gastrointestinal organs,
remain difficult to manage. At this age an increased rate of infection has been identified,
and gastrointestinal dysfunction is common [1,2,3,4,5,6]. Cardiovascular function
and sepsis are intimately related and may trigger early death without NICU or PICU
intervention [7]. Although the diagnostic procedures in newborns are often overlapping
with diagnostic algorithms used at older age, they continue to be a complex and dynamic
process which requires a proper investigation of the obstetrical and medical history,
skillful physical examination, appropriate laboratory tests, and imaging studies with
or without pathological examination of tissue biopsies. On the other hand, even with
these steps, diagnosis may remain elusive. The journey from the first appearance of
symptom or sign to the final diagnosis may seem sometimes interminable. Today, new
techniques seem to shorten this journey swiftly, and next-generation sequencing (NGS)
will play a major role in the next 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 developing
at a remarkable rate, particularly in pediatrics. Over the last few years, the pre-clinical
detection of pathologies has become more robust and efficient. In electronic libraries,
new biomarkers are being identified for several pathologies in neonatology and pediatrics.
Management of pediatric diseases may become extenuating, and the use of single nucleotide
polymorphisms for the improvement of our approach to some pediatric diagnostic algorithmic
failures targeting the interindividual variability may be considered. Pediatric trial
networks provide pediatricians, researchers, and agencies with new information on
how children may respond to drugs and medications. The present Special Issue collects
wet lab research and review articles to highlight some fields of pediatrics that may
shape future directions in the diagnosis and management of some diseases. Pediatric
heart failure is a challenge in neonatology and pediatrics, and quality assurance
criteria are key [7,8,9,10,11]. An open-heart surgery with cardiopulmonary bypass
(CPB) remains an interventional procedure accompanied by a high mortality/morbidity
rate. Satriano et al. investigated whether blood concentrations of glutathione (GSH),
a powerful endogenous antioxidant, changed in the perioperative period [12]. In the
perioperative period, the increase in GSH may suggest that a compensatory mechanism
to oxidative damage during surgical procedure takes place. The measurement of the
interferon (IFN) score has been suggested for the screening of monogenic interferonopathies,
like the Aicardi–Goutières syndrome. Moreover, it may be useful to stratify subjects
with systemic lupus erythematosus before receiving IFN-targeted treatments. Pin et
al. developed an approach to reduce the inter-laboratory variability [13]. These authors
provide shared strategies for the IFN signature analysis. They allow different centers
to compare data and merge their experiences. Diabetic retinopathy (DR) is a dramatic
and major microvascular complication of diabetes mellitus, and very few studies have
evidenced the magnitude of this disorder in the pediatric population [14]. The International
Society for Pediatric and Adolescent Diabetes (ISPAD) mandates that annual screening
for DR should be performed in patients aged 11 years after diabetes of 2 years’ duration
and from 9 years of age with diabetes of 5 years’ duration [15]. Kołodziej et al.
studied the width of individual retinal layers in patients with type 1 diabetes (T1DM)
correlating their data with markers of diabetes metabolic control applying the optical
coherence tomography (OCT) study performed using a high definition OCT Cirrus 5000
[16]. The authors found a positive correlation between center thickness and spectral-domain
for average glycemia and temporal CT with age at examination, suggesting that selected
parameters may be applied as potential markers of preclinical phase of DR in patients
with T1DM. Allen and Gupta highlight the current and nearest futuristic perspective
of “artificial pancreas” suggesting that soon such a system may not require any manual
patient input allowing patients to eat throughout the day without entering any blood
sugars or counting carbohydrates [17]. Such a device may be commercially available
as technology continues to advance in this direction using artificial intelligence.
Sarcoidosis is an inflammatory syndrome of non-necrotizing granulomatous type with
multisystemic manifestations, and its occurrence in pediatrics is not an isolated
finding any longer. Few cases have been reported of this intriguing disease in children
and youth [18]. Chiu et al. revised this topic in detail in this issue [19]. These
authors focused on early-onset sarcoidosis, high-risk sarcoidosis, and atypical sarcoid-related
diseases. Blau syndrome and early-onset sarcoidosis occur in children younger than
five years manifesting with extra-thoracic findings but usually without lymphadenopathy
and pulmonary involvement. Endoscopic bronchial ultrasound (EBUS) and transbronchial
fine-needle aspiration (TBNA) sampling of intrathoracic lymph nodes and lung may provide
good diagnostic yield and excellent patient safety profile in childhood. Respiratory
syncytial virus (RSV) bronchiolitis remains an important cause of morbidity in early
infancy. RSV belongs to the species of Orthopneumovirus. The human RSV (HRSV) infects
60% of infants during their first RSV season, and usually all children show an infection
record with this virus by 2–3 years of age [20]. Among the infants infected with RSV,
2–3% will develop bronchiolitis, necessitating hospitalization [21]. RSV bronchiolitis
is a major cause of infection and hospitalization in infancy and childhood worldwide.
Palivizumab can be employed to prevent this infection in preterm babies, infants with
certain congenital heart defects (CHD), infants affected with bronchopulmonary dysplasia
(BPD), and infants with congenital malformations of the airway. HRSV bronchiolitis
is treated with supportive care, including oxygen therapy, continuous positive airway
pressure (CPAP) or nasal high flow oxygen, as required. Rodriguez-Gonzalez et al.
identified that left ventricular myocardial dysfunction (LVMD) might occur in healthy
infants with HRSV bronchiolitis who develop severe disease and need to be treated
at the PICU [22]. N-terminal pro-B-type natriuretic peptide (NT-proBNP) seems to increase
the accuracy of traditional clinical markers in predicting the outcomes. Duvekot et
al. report a rare event complicating a common adenotonsillectomy. Subcutaneous and
mediastinal emphysema followed by group A beta-hemolytic streptococci mediastinitis
occurred in a young child, reminding us the life-threatening complications of such
surgical procedure [23]. Primary indications for adenotonsillectomy are obstructive
sleep apnea (OSA) and recurrent pharyngotonsillitis. Although there is evidence-based
medicine supporting the use of such surgical procedures on children affected with
OSA that is mainly derived on sleep studies, quality of life, and child behavior,
it seems that the impact of surgery on recurrent sore throat symptoms is less well
delineated. It has been indicated that children younger than three years and children
with OSA of moderate to severe degree, as well as infants affected with significant
comorbidities should be admitted for overnight observation. In most patients, simple
analgesia is adequate postoperatively, while codeine is contraindicated due to cases
of postoperative death as consequence of respiratory suppression. Pain and postoperative
hemorrhage (2–4%) are the most common complications, but bleeding can be life-threatening,
nevertheless the mortality rate remains small but substantial (1:30,000) [24]. Besides
tonsillar enlargement, salivary gland enlargement is a condition which enters in the
differential diagnosis of head and neck (H&N) masses. Branchial cysts, sialadenosis,
and inflammation of the salivary glands are often seen in childhood and youth, but
H&N malignant pathologies also need to be taken into consideration. Sergi et al. critically
review the diagnostic features of a pediatric mass of the H&N region [25]. Somatosensory
evoked potentials (SSEPs) are crucial in assessing the functional integrity of the
neural pathways and for predicting the outcome of perinatal injuries. Barkhuizen et
al. studied the translational potential of SSEPs together with sensory function in
rodents with perinatal hypoxic-ischemic events [26]. No group differences in the amplitude
or latency of the evoked potentials of the preceding sensory response were seen, but
nevertheless this method of study is intriguing for the functional recovery. Das and
van Landeghem revise the clinicopathological spectrum of bilirubin encephalopathy/kernicterus,
which is relatively rare but continues to occur despite universal newborn screening,
particularly in middle and low income countries [27]. The authors illustrate the array
of clinicopathological findings, and the procedures of diagnostic testing reported
to be key in the context of bilirubin encephalopathy and kernicterus. Khan and Sergi
report on sialidosis, which is a rare, autosomal recessive inherited disorder, caused
by α-N-acetyl neuraminidase deficiency resulting from a mutation in the neuraminidase
gene (NEU1) and accompanied by cerebral and extra-cerebral manifestations combining
the underlying molecular biology, the clinical features, and the morphological patterns
of this disorder [28].
Finally, the attention should be drawn to the frontispiece of this book. It is a photograph
of a famous sculpture of Horatio Greenough (6 September 1805–18 December 1852). He
was an American sculptor who was best known for his two United States government commissions,
“The Rescue” and “George Washington”, among others. Before graduating from Harvard,
Horatio Greenough sailed to Italy, Rome, to study art. There, the sculptor created
many busts. In 1833, he realized “The Ascension of a Child Conducted by an Infant
Angel” in marble. The gift to the Museum of Fine Arts in Boston, Massachusetts, United
States of America, is a marvelous and touching piece of art and may combine the most
elysian characteristics of all Greenough’s sculpture. Both the child and the angel
are animated by a deep serenity, which may deeply contrast to the austere Hadrian’s
words engraved in the sculpture support (Animula, vagula, blandula - Hospes comesque
corporis - Quae nunc abibis in loca Pallidula, rigida, nudula - Nec, ut soles, dabis
iocos? Little, suave, and wanderer soul, guest and partner of the body - Where are
you off to now? Somewhere without color, severe, and empty - Never will you participate
in gags as usual). Publius Aelius Hadrianus Augustus was a Roman emperor from 117
to 138 A.D., who died at the age of 62 years following a long and restless reign.
Suffering from hypertension and coronary atherosclerosis in the last years of his
life, he probably died of congestive heart failure as extensively reported by Dio
Cassius and the Historia Augusta records [29]. This suffering has probably shaped
some of his scripts. The “Ascension of a Child Conducted by an Infant Angel” conveys
an astonishingly gentle, warm, and attractive message of peacefulness, hope, and spirituality
in an age of high infant mortality. In 1911, Newmayer wrote that the country which
first recognizes its responsibilities to the child would be given the appreciation
of the world as being the leading civilized nation [30]. At this time, the United
States lagged in the child’s health and welfare, and the infant mortality rate (IMR)
positioned the United States as ranked in the 18th position out of 30 countries, with
a rate of 135 deaths per 1000 live births. Following the European example, US public
health leaders started a national campaign to reduce infant mortality, and, in 1912,
the US Children’s Bureau (USCB) was founded (Brosco 1999). Federal and state programs
multiplied and, progressively, pediatricians and children’s hospitals also surfaced
as the ideal supply of healthcare for children. The improvement of nutrition and treatment
of rickets were also crucial and the results of these efforts during the last century
have been impressive in all states consolidating the concept of pediatric healthcare
in other countries, such as Canada, as well [31]. Digitalization of the imaging in
radiology and pathology is a reality in several healthcare institutions worldwide
[32,33]. Advances in medical diagnosis and therapy with the implementation of new
technologies will be the basis for the future of pediatric healthcare, personalized
pediatrics, and quality assurance and controls in the 21st century.