Presepsin Levels in Pediatric Patients with Fever and Suspected Sepsis: A Pilot Study in an Emergency Department.

Sepsis is a life-threatening condition that affects 1.2 million children annually. Although there are several criteria for diagnosing this condition, signs are often nonspecific, and identifying sepsis is challenging. In this context, presepsin (P-SEP) seems to be a promising new biomarker since its plasma levels increase earlier than other sepsis-related proteins and its measurement is faster. We enrolled 157 minors who presented to the Pediatric Emergency Department of Agostino Gemelli Hospital with fever and suspected sepsis. Biochemical, anamnestic, and clinical data were collected. Viral agents were identified as the causative factor in 64 patients, who had an average P-SEP value of 309.04 pg/mL (SD ± 273.2), versus an average P-SEP value of 526.09 pg/mL (SD ± 657) found in 27 bacterial cases (p value: 0.0398). Four cases of overt sepsis had an average P-SEP value of 3328.5 pg/mL (SD ± 1586.6). The difference in P-SEP levels in viral versus bacterial infections was found to be statistically significant; therefore, P-SEP may have a central role in the evaluation of febrile children, helping clinicians distinguish between these two etiologies. Furthermore, amongst the cases of confirmed sepsis, P-SEP was always greater than 2000 pg/mL, while C-reactive protein and procalcitonin values appeared lower than what was considered significant.

Bone Disorders in Pediatric Chronic Kidney Disease: A Literature Review.

Intense changes in mineral and bone metabolism are frequent in chronic kidney disease (CKD) and represent an important cause of morbidity and reduced quality of life. These disorders have conventionally been defined as renal osteodystrophy and classified based on bone biopsy, but due to a lack of bone biopsy data and validated radiological methods to evaluate bone morphology in children, it has been challenging to effectively assess renal osteodystrophy in pediatric CKD; the consequence has been the suboptimal management of bone disorders in children. CKD-mineral and bone disorder (CKD-MBD) is a new expression used to describe a systemic disorder of mineral and bone metabolism as a result of CKD. CKD-MBD is a triad of biochemical imbalances in calcium, phosphate, parathyroid hormone, and vitamin D; bone deformities and soft tissue calcification. This literature review aims to explore the pathogenesis, diagnostic approach, and treatment of CKD-MBD in children and the effects of renal osteodystrophy on growing skeleton, with a specific focus on the biological basis of this peculiar condition.

Intranasal human-recombinant NGF administration improves outcome in children with post-traumatic unresponsive wakefulness syndrome.

BACKGROUND: Severe traumatic brain injury (TBI) is one of the most dramatic events in pediatric age and, despite advanced neuro-intensive care, the survival rate of these patients remains low. Children suffering from severe TBI show long-term sequelae, more pronounced in behavioral, neurological and neuropsychological functions leading to, in the most severe cases, an unresponsive wakefulness syndrome (UWS). Currently, no effective treatments can restore neuronal loss or produce significant improvement in these patients. In experimental animal models, human- recombinant Nerve Growth Factor (hr-NGF) promotes neural recovery supporting neuronal growth, differentiation and survival of brain cells and up-regulating the neurogenesis-associated processes. Only a few studies reported the efficacy of intranasal hr-NGF administration in children with post- traumatic UWS. METHODS: Children with the diagnosis of post-traumatic UWS were enrolled. These patients underwent a treatment with intranasal hr-NGF administration, at a total dose of 50 gamma/kg, three times a day for 7 consecutive days. The treatment schedule was performed for 4 cycles, at one month distance each. Neuroradiogical evaluation by Positron Emission Tomography scan (PET), Single Photon Emission Computed Tomography (SPECT), Electroencephalography (EEG), and Power Spectral Density (PSD) was determined before the treatment and one month after the end. Neurological assessment was also deepened by using modified Ashworth Scale, Gross Motor Function Measure, and Disability Rating Scale. RESULTS: Three children with post-traumatic UWS were treated. hr-NGF administration improved functional (PET and SPECT) and electrophysiological (EEG and PSD) assessment. Also clinical conditions improved, mainly for the reduction of spasticity and with the acquisition of voluntary movements, facial mimicry, attention and verbal comprehension, ability to cry, cough reflex, oral motility, and feeding capacity, with a significant improvement of their neurological scores. No side effects were reported. CONCLUSION: These promising results and the ease of administration of this treatment make it worthwhile to be investigated further, mainly in the early stages from severe TBI and in patients with better baseline neurological conditions, to explore more thoroughly the benefits of this new approach on neuronal function recovery after traumatic brain damage.

Pain management in pediatric age. An update.

Differently from the adult patients, in paediatric age it is more difficult to assess and treat efficaciously the pain and often this symptom is undertreated or not treated. In children, a selection of appropriate pain assessment tools should consider the age, the cognitive level, the presence of eventual disability, the type of pain and the situation in which it is occurring. Improved understanding of developmental neurobiology and paediatric analgesic drug pharmacokinetics should facilitate a better management of childhood pain. The objective of this update is to discuss the current practice and the recent advances in pediatric pain management.  Using PubMed and the Cochrane Library we conducted an extensive literature analysis on pediatric pain assessment and commonly used analgesic agents in this kind of patients. According to our results, a multimodal analgesic regimen provides a better pain control and a functional outcome in children. Cooperation and communication among the anaesthesiologist, the surgeon and the paediatrician remains essential for successful anaesthesia and pain management in childhood.

The Role of Sex Differences in Bone Health and Healing.

Fracture healing is a long-term and complex process influenced by a huge variety of factors. Among these, there is a sex/gender disparity. Based on significant differences observed in the outcome of bone healing in males and females, in the present review, we report the main findings, hypotheses and pitfalls that could lead to these differences. In particular, the role of sex hormones and inflammation has been reported to have a role in the observed less efficient bone healing in females in comparison with that observed in males. In addition, estrogen-induced cellular processes such as autophagic cell cycle impairment and molecular signals suppressing cell cycle progression seem also to play a role in female fracture healing delay. In conclusion, it seems conceivable that a complex framework of events could contribute to the female bias in bone healing, and we suggest that a reappraisal of the compelling factors could contribute to the mitigation of sex/gender disparity and improve bone healing outcomes.

Presepsin as a diagnostic marker of sepsis in children and adolescents: a short critical update.

BACKGROUND AND AIM: Sepsis is a potentially fatal condition which strikes 1.2 million children worldwide per year. New biomarkers have been proposed in the assessment of the risk of sepsis progression and in the identification of patients with the worst outcome. This review aims to assess the diagnostic value of presepsin, a promising new biomarker, in pediatric sepsis, with particular attention to its usefulness in emergency department. METHODS: We performed a literature search of the last 10 years to find presepsin related studies and reports concerning pediatric population aged from 0 months to 18 years. We mainly focused on randomized placebo-control studies, followed by case-control studies, observational (both retrospective or prospective), and finally systematic reviews and meta-analysis. The article selection process was carried out independently by three reviewers.   Results: A total of 60 records were identified in literature, 49 were excluded according to the exclusion criteria. The highest presepsin sensitivity value was 100%, with a high cut-off (800.5 pg/mL). The highest sensitivity-specificity ratio was 94% vs 100%, with a similar considered presepsin cut-off (855 ng/L). As regards the presepsin cut-offs reported in the various studies, several authors agree on a critical threshold of about 650 ng/L to guarantee a sensitivity> 90%. The analyzed studies show a wide variability for patients' age and presepsin risk cut-offs.   Conclusions: Presepsin seems to be a new useful marker for early diagnosis of sepsis, even in a pediatric emergency setting. Being a new marker of sepsis, more studies are required to better understand its potential.

Early treatment with N-acetylcysteine reduces hepatotoxicity in acute acetaminophen poisoning.

During the outbreak of COVID19 measures taken to contain the spread of the virus have influenced the mental well-being of adults and adolescents. Acetaminophen overdose is the major cause of drug intoxication among children and adolescents. We reported a case of a 15-year- old girl referred to our Emergency Department 3 hours after ingestion of 10 g of paracetamol for suicidal purposes. She promptly started the administration of intravenous N-acetylcysteine (NAC) and the patient was discharged after 5 days of hospitalization in good clinical condition and with neuropsychiatric follow-up. Our case shows that the timing of the intravenous NAC administration is considered the most important factor in the prevention of acetaminophen-induced hepatic failure, despite high serum levels after acetaminophen ingestion.

Combined treatment of nerve growth factor and transcranical direct current stimulations to improve outcome in children with vegetative state after out-of-hospital cardiac arrest.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is one of the most dramatic events in pediatric age and, despite advanced neurointensive care, the survival rate remains low. Currently, no effective treatments can restore neuronal loss or produce significant improvement in these patients. Nerve Growth Factor (NGF) is a neurotrophin potentially able to counteract many of the deleterious effects triggered by OHCA. Transcranial Direct Current Stimulation (tDCS) has been reported to be neuroprotective in many neurological diseases, such as motor deficit and cognitive impairment. Children with the diagnosis of chronic vegetative state after OHCA were enrolled. These patients underwent a combined treatment of intranasal administration of human recombinant NGF (hr-NGF), at a total dose of 50 gamma/kg, and tDCS, in which current intensity was increased from zero to 2 mA from the first 5 s of stimulation and maintained constant for 20 min. The treatment schedule was performed twice, at one month distance each. Neuroradiogical evaluation with Positron Emission Tomography scan (PET), Single Photon Emission Computed Tomography (SPECT), Electroencephalography (EEG) and Power Spectral Density of the brain (PSD) was determined before the treatment and one month after the end. Neurological assessment was deepened by using modified Ashworth Scale, Gross Motor Function Measure, and Disability Rating Scale. RESULTS: Three children with a chronic vegetative state secondary to OHCA were treated. The combined treatment with hr-NGF and tDCS improved functional (PET and SPECT) and electrophysiological (EEG and PSD) assessment. Also clinical conditions improved, mainly for the reduction of spasticity and with the acquisition of voluntary finger movements, improved facial mimicry and reaction to painful stimuli. No side effects were reported. CONCLUSIONS: These promising preliminary results and the ease of administration of this treatment make it worthwhile to be investigated further, mainly in the early stages from OHCA and in patients with better baseline neurological conditions, in order to explore more thoroughly the benefits of this new approach on neuronal function recovery after OHCA.

COVID-19 increased in Italian children in the autumn and winter 2021-2022 period when Omicron was the dominant variant.

AIM: We examined the prevalence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children during the autumn and winter season from 1 September 2021 to 30 January 2022 and compared it with the same period in 2020-2021. METHODS: This study was carried out int the paediatric emergency department (PED) of a tertiary Italian hospital. We compared the clinical and demographical features of all children who presented during the two study periods and tested positive for SARS-CoV-2. RESULTS: During the 2021-2022 autumn and winter season 5813 children presented to the PED, 19.0% were tested for SARS-CoV-2 and 133 (12.0%) of those tested positive. In 2020-2021, 2914 presented to the PED, 12.3% were tested, and 30 (8.3%) of those tested positive. There were no statistically significant differences in clinical severity during the two study periods, despite a higher percentage of neurological symptoms in 2020-2021. Of the SARS-CoV-2-positive cases, 29/133 (21.8%) were hospitalised during the 2021-2022 season and 10/30 (33.3%) during the previous one. Only 3/163 children required intensive care. CONCLUSION: The greater spread of SARS-CoV-2 was probably due to the greater transmissibility of the Omicron variant, but the symptoms were mild and only 3 children required intensive care.

The impact of constipation on pediatric emergency department: a retrospective analysis of the diagnosis and management.

BACKGROUND AND AIM: Functional constipation (FC) represents 95% of pediatric constipation cases. The aim of this study was to assess the prevalence of Functional Constipation in children admitted to Pediatric Emergency Department (ED) with acute abdominal pain, the demographic factors associated, the use of imaging exams and laboratory tests. METHODS: A retrospective observational study was conducted on 4100 medical records of children aged 0 to 18 years. RESULTS: Among children with abdominal pain, 11.3% of them had a discharge diagnosis of constipation and 45.5% underwent imaging exams. Most of children (93.9%) were discharged with home therapy and 6.5% of patients needed of additional visits. In ED 6.7% of patients underwent enema, 45.2% were discharged with indication to perform it at home. CONCLUSIONS: FC is a medical condition that could be managed in the outpatient setting, even if we observed a significant percentage of cases in ED. We observed over-utilization of radiologic tests, whereas the diagnosis should be clinical.

Foreign Body Ingestion in Children: Epidemiological, Clinical Features and Outcome in a Third Level Emergency Department.

Ingestion of foreign bodies is a frequent pediatric cause of access to the Emergency Department (ED). The aim of this study was to determine the epidemiological and clinical features of pediatric patients with a diagnosis of foreign body ingestion and to identify the factors associated with an urgent invasive procedure or hospitalization. This is a retrospective study conducted on a population of 286 pediatric patients (0-17 years) evaluated for foreign body ingestion at the Pediatric ED of "Fondazione Policlinico Universitario A. Gemelli, IRCSS" between October 2014 and June 2019. Data concerning age and gender, underlying diseases, type of foreign body, symptoms and signs, instrumental tests, specialist visits, treatment and outcome were analyzed. The majority of foreign bodies were coins (23%). Symptoms recurred in 50% of the foreign bodies with esophageal localization and between the 92 (32%) patients with symptoms the most common was vomiting (7%). X-rays was performed in 61% of patients. Among all patients, 253 patients (88.8%) had been discharged, 21 (7%) had been hospitalized, and four (1.4%) were sent to an outpatient facility. Besides, 17 (5.9%) patients had been transferred to the Observation Unit. Of the hospitalized patients (21 (7.3%)), clinical observation was performed for 57% and endoscopic procedure for 45%. Our data confirm that the ESPGHAN-ESGE guidelines application prevents interventions that are not necessary, avoiding diagnostic and therapeutic delays.

Cytokine Response to SARS-CoV-2 Infection in Children.

The causal connection between serum biomarkers and COVID-19 severity or pathogenicity in children is unclear. The aim of this study was to describe clinical and immunological features of children affected by COVID-19. The secondary aim was to evaluate whether these cytokines could predict severity of COVID-19. All children (aged 0-18) admitted to the Pediatric Emergency Department and tested with nasopharyngeal swab for SARS-CoV-2 were recruited and assigned to three groups: COVID-19, other infections, control group. Clinical and laboratory data of these patients, including circulating cytokine levels, were analyzed in three groups. Fever was the most frequent symptom in COVID-19 (67.3%). Neutropenia was found in the COVID-19 group (p < 0.05); no difference was observed for lymphocyte counts in the three groups. Higher levels of IL-6 and TNF-alpha were found in the COVID-19 group compared to other infections and control groups (p = 0.014 and p = 0.001, respectively). Whereas, in the COVID-19 group, no difference was observed as for the same cytokines among sub-groups of different disease severity (p = 0.7 and p = 0.8). Serum levels of IL-6 and TNF-alpha were higher in COVID-19 children than in children with other infectious diseases, but those levels did not correlate with disease severity. Clinical studies in a large pediatric population are necessary to better define the role of the immune-mediated response in SARS-CoV-2 infections in children.

Utility of a pediatric observation unit for the management of children admitted to the emergency department.

BACKGROUND: Observation Units (OU), as part of emergency department (ED), are areas reserved for short-term treatment or observation of patients with selected diagnoses to determine the need for hospitalization or home referral. METHODS: In this retrospective cohort study, we analyzed similarities and differences of children admitted to the pediatric ED of the Fondazione Policlinico Universitario A. Gemelli IRCCS hospital in the first 2 years of OU activity, analyzing general patient characteristics, access modalities, diagnosis, triage, laboratory and instrumental examinations, specialist visits, outcome of OU admission and average time spent in OU. Furthermore, we compared total numbers and type of hospitalization of the first 2 years of OU activity with those of previous 2 years. RESULTS: The most frequent diagnoses were abdominal pain, minor head injury without loss of consciousness, vomiting, epilepsy and acute bronchiolitis. The most performed laboratory examinations were blood count. The most commonly performed instrumental examination was abdominal ultrasound. Neurological counseling was the most commonly requested. Average time spent in OU was 13 h in 2016 and 14.1 h in 2017. Most OU admissions did not last longer than 24 h (90.5% in 2016 and 89.5% in 2017). In the years 2014-2015, 13.4% of pediatric patients accessing the ED were hospitalized, versus 9.9% the years 2016-2017 reducing pediatric hospital admissions by 3.6% (p <  0.001). CONCLUSIONS: This study demonstrate that OU is a valid alternative to ordinary wards for specific pathologies. In accordance with the literature, our study showed that, in the first 2 years of the OU activity, admissions to hospital ward decreased compared with the previous 2 years with an increase of complex patients.

Air bronchogram integrated lung ultrasound score to monitor community-acquired pneumonia in a pilot pediatric population.

AIMS: Chest ultrasound is a non-invasive method for evaluating children with suspected community-acquired pneumonia (CAP). We evaluated the prognostic role of change of ultrasonographic (US) air bronchogram in management of CAP in terms of: rate of complicated CAP, change of empiric antibiotic therapy, relationship to defervescence time, and length of hospitalization. METHODS: Patients with CAP and radiographic evidence of lung consolidation were prospectively enrolled. Chest US examinations were performed within 12 h from admission and after 48 h. A new grading system (USINCHILD score) based on presence and features of air bronchogram was adopted. RESULTS: Thirty six patients were stratified into two groups according to the presence of an increase of at least 1 grade of US score (Δ US grade), expression of an improvement of lung consolidation. Δ US grade after 48 h ≥ 1 was associated with an increased risk of complicated CAP (p value 0.027) and a longer defervescence time (p value 0.036). Moreover, Δ US grade ≥ 1 was predictive of a short hospitalization (p value 0.008). CONCLUSIONS: USINCHILD score could be an innovative biotechnology tool for the management of pediatric CAP. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: NCT03556488, June 14, 2018.

Short therapy in a septic arthritis of the neonatal hip.

Septic arthritis (SA) is a serious joint infection associated with significant morbidity that can cause permanent damage with articular cartilage destruction, osteonecrosis and lifelong deformities if not diagnosed and treated promptly. In neonates, because of the paucity of signs and symptoms, SA is difficult to diagnose. The treatment for SA in children is empirical antibiotic for weeks, initially intravenously, and surgical (arthrotomy) in particular for the hip and shoulder because of the high risk of sequelae in these joints. Actually, there isn't a consensus about the duration of antibiotic treatment, because of the lack of powered studies, and a variable period from 2 weeks to 4 months has been suggested in the literature. Data in the neonatal population are very limited. We describe a case of neonatal hip arthritis with a good outcome treated with a short antibiotic course of 2 weeks.