Increased serum levels of proNGF, mature NGF and interleukins in burn-injured children.

OBJECTIVE: Burns are among the most common injuries in children. In burns of more than 20% of the total body surface area, a systemic inflammatory response involving several chemical mediators occurs. Among them, nerve growth factor (NGF) regulates the inflammatory response related to wound healing and promotes keratinocyte proliferation and angiogenesis. The aim of our study was to investigate the physiological response to injury in children with moderate-severe burns, assaying proNGF, mature NGF (mNGF), interleukins (IL)-1ß, and Il-10 serum levels. PATIENTS AND METHODS: This is a prospective observational study, including twelve children hospitalized for moderate-severe burns at the Gemelli Hospital (Rome). Their laboratory features were compared to those of patients with obstructive hydrocephalus who underwent surgery. RESULTS: Our results showed an increase in proNGF and mNGF serum levels. In burn patients, proNGF levels increased before mNGF, and serum concentrations of both were not correlated with burn extension and depth. The most significant levels of mNGF and proNGF were reported in scalds involving the face. Serum IL-1ß and IL-10 peak levels were reached with a time-course pattern similar to proNGF. CONCLUSIONS: Our preliminary results validate the hypothesis that serum levels of proNGF and mNGF may represent inflammatory biomarkers useful for monitoring burn patients and defining new strategies for their treatment.

Single-center, prospective, and observational study on the management and treatment of impetigo in a pediatric population.

OBJECTIVE: Ozenoxacin is a new antibiotic used to treat non-bullous impetigo. The aim of this study is to evaluate the microbiological and clinical efficacy of topical ozenoxacin 1% cream after 5-day twice-daily treatment, in pediatric patients with impetigo. PATIENTS AND METHODS: This observational and prospective study included patients aged 6 months to 18 years, with non-bullous impetigo. Efficacy was measured using the Skin Infection Rating Scale (SIRS) and microbiological culture at the first visit (T0), at the second visit after 72 hours (T1) and after 5 days (T2). Safety and tolerability were also evaluated. RESULTS: A total of 50 patients was enrolled. A reduction of SIRS score >10% after 72 hours of treatment was noticed in all patients, while a complete reduction was assessed after 5 days in all the population. Microbiologic success rates for ozenoxacin at T1 was 92% (four patients had original pathogens in the specimen culture from the skin area), whereas at T2, it was 100%. CONCLUSIONS: Topical ozenoxacin has strong efficacy in treating impetigo in pediatric patients. Ozenoxacin's clinical and microbiological rapid onset of response led to consider this antibiotic a novel efficacy option for the treatment of impetigo.

Non-pharmacologic approaches to neurological stimulation in patients with severe brain injuries: a systematic review.

OBJECTIVE: This review aimed to evaluate and summarize the current knowledge about the non-pharmacological neurological stimulation (NPNS) in patients with severe brain injuries (SBI). The approaches we analyzed included sensory stimulation, music therapy, virtual reality, transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS). MATERIALS AND METHODS: We performed a review following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) standards. The key words used for the search across electronic databases such as PubMed and the Cochrane Library were "brain injury" or "coma" or "vegetative state" and "neurological stimulation" or "sensory stimulation" or "music therapy" or "virtual reality" or "transcranial direct current stimulation" or "transcranial magnetic stimulation". RESULTS: 38 studies matched the inclusion criteria. These articles were categorized into five clusters: sensory stimulation, music therapy, virtual reality, transcranial direct current stimulation and transcranial magnetic stimulation. Hence, a concise summary of each study was made up, including study population characteristics, type of non-pharmacological neurological stimulation, neurological clinical outcomes or neuroimaging outcomes. CONCLUSIONS: Overall, all the non-pharmacological approaches to neurological stimulation in patients with SBI seem to be innovative and promising. Further randomized clinical trials, including a wide range of patients, will be necessary to definitely validate these methods and develop standardized protocols shared in the scientific community.

Role of the pupillometer in the assessment of pain in the sedation of pediatric patients.

OBJECTIVE: Pupillometry has been used to assess pain intensity and response to analgesic drugs in adults. The aim of this study was to verify the usefulness and effectiveness of the pupillometer to assess pain and depth of sedation in pediatric patients undergoing painful procedures and to optimize pain management by observing pupillary variations induced by opioids. PATIENTS AND METHODS: This is a prospective, monocentric study conducted in the sedation room of the Pediatric Intensive Care Unit of Fondazione Policlinico A. Gemelli in Rome. A population of 22 pediatric patients who underwent painful procedures was enrolled. Eleven children were sedated by opioid drugs. Heart rate, systolic blood pressure, diastolic blood pressure, bispectral index, maximum pupil size (Size), pupil change (CH), Neurological Pupil Index (NPi) were collected over four times: before starting the procedure; before the painful stimulus (when the patient was sedated); when the painful stimulus was applied; at the end of the procedure. A NeurOptics NPi-200 pupillometer was used for the study. RESULTS: Statistical significance in the variation of haemodynamic parameters was less significant than the variation obtained by analyzing the pupillary parameters: a significant change in NPi and CH in the transition from wakefulness to sedation and from the application of the painful stimulus to awakening was found in both study populations, patients who have received opioids and patients who have not received opioids. Changes in the mean CH of the pupil diameter correlate with the depth of sedation, and the size values vary in relation to the administration of opioids. CONCLUSIONS: Our findings highlight the potential role of pupillometry as a non-invasive method to objectively quantitate pain response in children to reach an efficient analgesic approach.

Early spontaneous pneumothorax, pneumomediastinum and pneumorrhachis in an adolescent with SARS-CoV-2 infection.

We report a case of spontaneous pneumomediastinum, pneumothorax, emphysema subcutaneous and pneumorrhachis, occurring in an adolescent resulting positive to SARS-CoV-2 nasopharyngeal swab. At the admission in Emergency Department, the child presented with left cervical and sternal pain, without respiratory symptoms. Radiological studies showed sizeable pneumomediastinum, bilateral apical pneumothorax, massive emphysema subcutaneous and pneumorrhachis. Patients' clinical conditions stood stable during the monitoring and he only needed conservative management. To our knowledge, this is the first description of spontaneous pneumomediastinum, pneumothorax, emphysema subcutaneous and pneumorrhachis, in a COVID-19 adolescent without concomitant pneumonia.

Effect of Lactobacillus reuteri LRE02-Lactobacillus rhamnosus LR04 combination and gastrointestinal functional disorders in an Emergency Department pediatric population.

OBJECTIVE: Probiotics are living microorganisms that, when administered per os in adequate amounts, may confer a health benefit on the host by the regularization of an unbalanced gastroenteric microbiota. The objective of this study was to evaluate treatment effectiveness, safety, and palatability of a probiotic's combination (Lactobacillus reuteri LRE02-DSM 23878 and Lactobacillus rhamnosus LR04-DSM 16605) in a pediatric Emergency Department setting with functional gastrointestinal disorders. PATIENTS AND METHODS: Three groups were enrolled: children with functional abdominal pain; children with gastroenteritis; children with gas colic. Self-reporting sheets were delivered to each patient/parent after probiotics treatment. The primary outcome was to evaluate the evolution of clinical conditions in enrolled children. RESULTS: The outcomes showed a statistical difference among children treated with probiotics and those who did not. In the functional abdominal pain group, 58.2% of patients had a moderate symptoms improvement and 33.5% had a complete disappearance of symptoms, while in the gas colic group, 68.2% of the infants had a moderate improvement and 23.2% had a complete resolution. In the gastroenteritis group, stool consistency and number of evacuations improved in children who took probiotic administration as well. CONCLUSIONS: Probiotics therapy, at the recommended dosage of five drops per day for 15 days, is associated with symptoms improvement. Moreover, the use of probiotics led to a stool consistency's normalization in a shorter time, evaluated with BSS. A randomized trial is needed to confirm these results.

Abdominal pain in children: the role of possible psychosocial disorders.

OBJECTIVE: To evaluate the relationship between functional abdominal pain and biopsychosocial factors: the current diagnostic criteria show limits. PATIENTS AND METHODS: This is a retrospective cohort study conducted in paediatric emergency department (ED) of a tertiary hospital in Rome. Children (0-18 years) evaluated for abdominal pain in the paediatric ED between January 2018 and December 2018 were enrolled. Patients were divided in 2 groups: organic and functional groups. The main outcome was the prevalence of different subtypes of functional disorders (according to Rome IV criteria) and the role of possible biopsychosocial disorders related to patients with functional symptoms. RESULTS: In this study, 1130 patients were included. In the functional group, 37.6% of patients were classified as affected by functional dyspepsia, 26.7% by functional abdominal pain-non otherwise specified (FAP-nos), 20.8% by inflammatory bowel syndrome (IBS), and 15.9% by abdominal migraine. Children of our functional sample reported at least one of the items present in the inventory CSSI-24 (24-item Children's Somatic Symptoms Inventory), but more than 50% reported at least 4 of the items investigated. CONCLUSIONS: At 6 and 12 months follow up and, new prospective studies on these disorders could improve the inclusion criteria for FGIDs, thinning the dubious rate of patients expected from the literature on the Rome IV criteria.

Telephone consultation during Coronavirus outbreak in a Pediatric Emergency Department: methodological approach of a tertiary care center in a COVID-19 hospital setting.

OBJECTIVE: A computerized system of telephone consultation has been experimented at the Pediatric Emergency Department (ED) of Policlinico Gemelli Hospital in Rome during the outbreak of Coronavirus Disease 2019 (COVID-19). MATERIALS AND METHODS: Twenty monothematic items with a series of questions to evaluate child's clinical conditions have been set up in order to evaluate the different situations according to their severity. All items were highlighted according to conventional scores corresponding to the different answers (yes/no) given by the child's parents. This system has been implemented with large diffusion of computer programs and applications by the availability of a computer station in every ED room. RESULTS: The system allows healthcare workers to establish the medical check-up urgency which may be immediate, within the next 24 hours or scheduled in the pediatric ward. Therefore, it has been implemented a telephone triage consultation with a standardized method. CONCLUSIONS: Telephone consultation during outbreaks, considering the risks of contagion, allows healthcare workers to decrease the concern of families and to reduce indiscriminate access to ED. The remote approach will not solve logistic and setting problems related to COVID-19 outbreak17, but it would be a valid tool to improve medical evaluation without deep change in infrastructure and clinical organization.

Dietary approach to prevent obesity risk in Spina Bifida patients.

PURPOSE: The aim of this prospective, analytic study is to evaluate if dietary approach can improve the body mass index (BMI) in a total of N = 152 patients with SB. METHODS: BMI levels were evaluated stratifying patients by gender and age classes. Patients with BMI ≥ 25 have been randomized (1:1) in two groups: the "diet" group that received a dietary program and the "no diet" group that did not receive any program. Patients have been observed at the beginning of the study (T0), and again at the end of the study, 1 year later (T1). The main objective of the study was to evaluate BMI score in SB patients and how it could be influenced by dietary changes. RESULTS: A total of 36.8% patients were classified as overweight or obese. Females present a mean BMI level higher than male, and patients older than 20 years old present the highest mean BMI. The "diet" group BMI decreased from 29.7 (± 3.8) to 27.7 (± 3.7) during the year of program. The mean BMI in the "no diet" group decreased from 30.3 (± 4.6) to 29.2 (± 4.7). There was a statistically significant difference in BMI level between groups (p < 0.0005). There was a statistically significant effect of time on BMI levels for the "diet program" group (p = 0.001), and there was NOT a statistically significant effect of time on BMI levels for the "no diet group" (p = 0.053). CONCLUSIONS: Spina Bifida population has high risk of obesity which is related to other comorbidities such as diabetes and hypertension for example. Specific dietary program, since pediatric age, correlates with an improvement of quality of life, a reduction of BMI and of risk of related diseases with obesity. This study confirms that the transition to adulthood marks the beginning of the overweight status for many SB patients, but it also demonstrates that, following a dietary program, even disabled patients with limited training capabilities can achieve a BMI reduction.

Paroxysmal non-epileptic events in the pediatric emergency department.

Paroxysmal non-epileptic events (PNEs), or pseudoseizures (PS) resemble epileptic seizures. They are considered part of a personality disorder and have a higher incidence among adolescents. Patients describe episodes (lasting up to 20 minutes) of loss of consciousness, twitching or jerking and unusual emotional states. Unlike epileptic seizures, they are not associated with electroencephalographic abnormalities. Distinguishing epileptic seizures from PNEs is not easy. 20% of patients with seizures have a final PNEs diagnosis but recognizing them on the first examination is difficult. Due to the severe initial clinical presentation, these patients are often admitted in the Pediatric Intensive Care Unit (PICU) and may be over-treated. We report two cases admitted to our PICU for apparent status epilepticus, in which the final diagnosis was PNEs.

Spontaneous pulmonary air embolism in a child undergoing procedural deep sedation: case report and review of the literature.

We performed a systematic review of the literature starting from a real case of venous air embolism (VAE) in a young infant undergoing central catheterization during procedural sedation. Air embolism due to internal jugular vein catheterization during procedural sedation is very rare, but it is a potentially life-threatening complication of central catheterization that warrants attention. To our knowledge, this is the first case published in a similar scenario.

Intranasal drug administration for procedural sedation in children admitted to pediatric Emergency Room.

OBJECTIVE: Pain relief is a very important aspect in Pediatrician's clinical practice. It is often thought that young children, particularly infants, do not perceive as much pain as adults because of their immature nervous system and that untreated pain would not have adverse long-term consequences. Instead, it has been demonstrated that infants and children experience pain in a similar manner to adults. Many factors, particularly emotional factors, can increase the child's pain perception. Children live with anxiety even minor procedures. This suggests the need for an adequate sedation and the way of sedation should be free of pain itself. We believe the route to be followed may be the intranasal (IN) administration of sedative drugs. MATERIALS AND METHODS: We have conducted a brief review of the literature by Pubmed about the most commonly used sedative drugs: sufentanyl, fentanyl, midazolam, ketamine, nitrous oxide and dexmedetomidine. We have investigated in the literature the type of administration of IN drugs: drop instillation or by a mucosal atomizer device (MAD). RESULTS: In our study, it was noted that IN drugs administration is an effective and safe method to reduce anxiety and to deliver analgesia because it is practical and non-invasive. Moreover, therapeutic levels of sedatives are low due to the presence of a rich vascular plexus in the nasal cavity, which communicates with the subarachnoid space via the olfactory nerve and reduce the time of medication delivery, that is, the onset of action. The use of MAD even gives as better bioavailability of drugs. CONCLUSIONS: IN sedation via MAD is effective and safe and should be one of the first choices for procedural sedation in children.

Pneumopericardium, pneumomediastinum, and pneumorrachis complicating acute respiratory syncytial virus bronchiolitis in children.

OBJECTIVE: We report 2 children with Respiratory Syncytial Virus (RSV) infection complicated with spontaneous pneumopericardium (PP) and pneumomediastinum (PM), one also associated with pneumorrhachis (PR). PATIENTS AND METHODS: Two previously healthy children presented with fever, violent dry cough, dyspnea, and tachypnea. Chest X-ray and CT scans showed sizeable PP and PM in both patients. One of them also presented PR. Children were initially treated with intravenous antibiotics, antipyretics, and a cough sedative. Because of worsening of respiratory distress syndrome, children underwent helmet-delivered CPAP with oxygen supplementation. The patients' clinical conditions quickly improved and they were discharged in good conditions. RESULTS: Pathogenetic mechanism of spontaneous PP and PM complicating RSV infection could be related to the cough, causing intrathoracic pressure increase and rupture of alveoli near the mediastinal pleura. Nevertheless, RSV seems to play a role in facilitating such complications, attenuating the cough threshold in infected children. CONCLUSIONS: RSV bronchiolitis can lead respiratory and systemic consequences, so their prompt recognition is essential to establish a fast and adequate therapy, especially control of cough and respiratory distress syndrome treatment.

Nerve Growth Factor (NGF) up-regulation in the cerebrospinal fluid of newborns with myelomeningocele.

BACKGROUND: Neurotrophic factors, such as Nerve Growth Factor (NGF), play a key role in the stimulation of sprouting, synaptic plasticity, and reorganization after spinal cord damage. AIM: The aim of this study was to investigate the expression of nerve growth factor (NGF) in the cerebrospinal fluid (CSF) of newborns with myelomeningocele (MMC) and to determine its correlation with this spinal malformation. PATIENTS AND METHODS: To measure the expression of NGF, we collected CSF samples of 14 newborns with MMC taken immediately before the neurosurgical correction of the spinal malformation and of 14 matched controls. Endogenous NGF levels were quantified using a two-site immuno-enzymatic assay. The statistical analysis was performed using the Mann-Whitney two-tailed two-sample test. RESULTS: In the CSF of patients with MMC, NGF levels showed a significant increase compared to the mean levels of the control group (63.05 ± 7.3 vs 18.32 ± 4.5 pg/mL; (p < 0.001). No correlation was found between NGF expression and different types of MMC malformation, such as the level of spinal lesion and the association with Chiari II syndrome. CONCLUSIONS: Our study shows an over-expression of NGF in the CSF of newborns with MMC. The observed pattern of NGF up-regulation in this subset of patients may stimulate axonal sprouting and synaptic reorganization of the damaged neural cells at the site of spinal cord injury, thereby representing an important biochemical marker of spinal cord damage in MMC patients.

Five years of experience in nocturnal enuresis and urinary incontinence in children: where we are and where we are going.

BACKGROUND: Nocturnal enuresis (NE) is a very common pediatric disorder. The aim of this study was to evaluate the characteristics of patients with NE or urinary incontinence (UI) during a period of 5 years to increase the knowledge on these conditions and optimize their diagnosis and treatment. METHODS: We enrolled 278 children with NE or UI referred to the pediatric nephrology ambulatory, 'A. Gemelli' University Hospital of Rome, from December 2006 to December 2011. RESULTS: We observed that heredity, parasomnias, left-handedness, polythelia and constipation are correlated to NE and UI. CONCLUSIONS: We wanted to clarify the definition of NE and UI and describe our experience on the main characteristics of these conditions by referring to the latest knowledge reported in the literature.

Current practice and recent advances in pediatric pain management.

BACKGROUND: Differently from the adult patients, in pediatric age it is more difficult to assess and treat efficaciously the pain and often this symptom is undertreated or not treated. In children, selection of appropriate pain assessment tools should consider age, cognitive level and the presence of eventual disability, type of pain and the situation in which it is occurring. Improved understanding of developmental neurobiology and paediatric analgesic drugs pharmacokinetics should facilitate a better management of childhood pain. AIM: The objective of this review is to discuss current practice and recent advances in pediatric pain management. METHODS: Using PubMed we conducted an extensive literature review on pediatric pain assessment and commonly used analgesic agents from January 2000 to January 2012. CONCLUSIONS: A multimodal analgesic regimen provides better pain control and functional outcome in children. Cooperation and communication between the anaesthesiologist, surgeon, and paediatrician are essential for successful anaesthesia and pain management.

Propofol/alfentanil and propofol/ketamine procedural sedation in children with acute lymphoblastic leukaemia: safety, efficacy and their correlation with pain neuromediator expression.

Invasive procedures, such as the lumbar puncture, can cause anxiety and pain in children undergoing treatment for acute lymphoblastic leukaemia (ALL). We investigated the safety and efficacy of two different protocols for analgo-sedation in 20 children with ALL undergoing lumbar puncture. We have conducted a prospective, cross-over study. Protocol A was composed of an association between propofol and alfentanil. Protocol B consisted in the combination of propofol and ketamine. We also evaluated the levels of nerve growth factor, substance P and enkephalins in the cerebrospinal fluid of these patients. All patients showed a satisfactory sedation and analgesia. We found a statistically significant difference of vital parameters between protocol A and protocol B, while there were no significant differences between sedation scores and the other parameters evaluated. Patients in protocol A showed a higher incidence of major side effects, such as respiratory depression. Pain neuromediator levels did not show any statistical difference between the two groups. This study shows that both protocols are effective to obtain a good sedation and analgesia in children with ALL undergoing lumbar puncture, but the association between propofol and ketamine appears to be safer due to the lower incidence of side effects.

Multiwalled carbon nanotube buckypaper: toxicology and biological effects in vitro and in vivo.

AIM: We evaluated the effect of buckypaper (BP) on cancer and primary cell lines in vitro and in vivo in laboratory rats. BP is an innovative material with interesting physical/chemical properties that has possible pharmacological and prosthetic employment. Given that precautions need to be taken where carbon nanotubes are injected into human body for drug delivery, as contrast agent-carrying entities for MRI or as the material of a new prosthesis generation, we assessed the toxicity of BP carbon nanotubes. BP has structural resemblance to asbestos, whose toxicity has been linked to cancer. RESULTS: BP decreased proliferation of human colorectal, breast and leukemic cancer cell lines in vitro. However, BP had no effect on the proliferation and viability of normal human arterial smooth muscle cells and human dermal fibroblasts in vitro. in vivo, BP induced a moderate inflammatory reaction but had no mutagenic effects. After BP implantation the animals showed an inflammatory reaction followed 2 weeks later by a cicatrization reaction with the organization and fibrosis of the scar. CONCLUSION: These results show a low toxicity of BP both in vitro and in vivo.