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.

Acrodermatitis enteropathica during parenteral nutrition: a pediatric case report.

Background and aim Acrodermatitis enteropathica is a rare disorder characterized by the triad composed by dermatitis, alopecia and diarrhoea. Its acquired form can be caused by inadequate zinc intake, malabsorptive processes, excessive renal or intestinal loss. A rare cause of acquired zinc deficiency is iatrogenic nutritional deficiency due to parenteral nutrition. The diagnosis can be really difficult because the early clinical signs are non-specific and patient's eventual comorbidities can often mask symptoms. Methods: A 5-years-old child affected by several comorbidities, consequent to C. Koseri meningo-encephalitis occurred in the neonatal period, was admitted to Pediatric ward for acute pancreatitis and  had been fed via total parenteral nutrition for one month. Symptoms started approximately 15 days after the start of a  standardized parenteral nutrition mixture. The child presented with diarrhoea, alopecia and erythematous bullous skin lesions, distributed predominantly in acral and periorificial sites and not responsive to topical treatments. Zinc serum dosage were very low (10 µg/dL, with normal values 68-107 µg/dL). Clinical improvement was very fast after oral zinc supplementation (5mg/daily), with a rapid regularisation in the intestinal habits and re-epithelialization of the skin lesions. Results and Conclusions: Trace elements are an essential component of parenteral nutrition. The supplementation of trace elements is an important part of the parenteral nutrition prescription. Even few days of zinc shortage, especially in frail patients, may cause a severe dermatitis that can be easily prevented. Despite its rarity, acrodermatitis enteropathica should be strongly considered in the differential diagnosis of skin lesions for these patients.

An Interesting Case of Neonatal AKI: What Is the Time to Consider Anuria Irreversible?

Acute kidney injury is a frequent complication for critical newborns. Its management is a significant challenge, especially in extremely low-birth-weight (ELBW) infants. Currently, peritoneal dialysis (PD) is the most manageable treatment. However, data are lacking regarding when diuresis can be declared irreversible relative to the start of PD. A female infant born at 28 + 0 weeks with a birth weight of 800 g by monochorionic diamniotic pregnancy, complicated by twin-to-twin transfusion syndrome, developed acute renal failure on the second day of life because of long-term intrauterine hypoperfusion. PD was started on day 7. The patient remained anuric until the 52nd day of dialysis, when she presented adequate urine output of 2.5 mL/kg/h and PD was suspended for 11 days. After an episode of sepsis, PD was re-started, and after 50 days of treatment, given a urine output of 1.5 mL/kg/h, it was discontinued. The patient died on day 132 after a disseminate infection, which led to multiorgan failure. In ELBW infants, PD is a valid therapeutic instrument to treat patients with renal failure. Despite the evidence of low renal functional reserve in these patients, the duration of recovery from diuresis after a period of anuria can be very long.

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.

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.

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.

The acute bronchiolitis rebound in children after COVID-19 restrictions: a retrospective, observational analysis.

BACKGROUND AND AIM: Bronchiolitis represents the main cause of illness and hospitalization in infants and young children. The aim of this study was to compare the Pediatric Emergency Department (PED) admissions for bronchiolitis during the post-COVID (Coronavirus disease) period to those of previous seasons and to analyze their etiology during COVID and post-COVID period. METHODS: We compared demographics, clinical and microbiological data of children admitted to PED with bronchiolitis between September 2021 and March 2022 (post-COVID period) to the previous seasons (COVID and pre-COVID period). RESULTS: During the post-COVID period the bronchiolitis season started earlier than usual, with a peak reached in November 2021; a gradual reduction was subsequently observed between December 2021 and January 2022. Our data showed a prevalence of High Priority code in children admitted to the PED with bronchiolitis during the post-COVID period (61.4%) compared the pre-COVID period (34.8%) (p=0.00). Also regarding the hospitalization of these patients, we found a major rate of hospitalization during this epidemic season (p=0.035). In addition, only 4 (1.5%) of the tested children resulted positive for SARS-CoV-2 and all of them were admitted to PED during the post-COVID period. The search for the other respiratory viruses showed during the current season a prevalence of respiratory syncytial virus (RSV) (60.2%), followed by Human Rhinovirus (30.1%). CONCLUSIONS: The post-COVID period was characterized by an early and short-term peak in acute bronchiolitis, with an increased rate of hospitalization. In addition, SARS-CoV-2 infection was rarely cause of bronchiolitis in children under 2 years old.

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 Effects of COVID-19 Pandemic on Italian School-Aged Children: Sleep-Related Difficulties and Trauma Reactions.

PURPOSE: The COVID-19 pandemic has affected the mental and physical health of the world population. This study aims to investigate incidence of sleep-related difficulties and post-traumatic stress disorder in the school-aged children after 1 year of the pandemic. METHODS: A sample of Italian children (6-12 years) was queried about their sleep behaviors after 1 year of the pandemic, answering the Children's Sleep Habits Questionnaire (CSHQ). We also evaluated trauma symptoms with the Children's Impact of Event Scale (CRIES-8). RESULTS: Among 205 participants, 184 (89.8%) presented sleep-related difficulties. Out of all, 99 (48.3%) had a high risk to develop post-traumatic stress disorder. Ninety-five (51.6%) children with sleep-related difficulties also presented an abnormal CRIES-8 total score. A correlation was found between the CSHQ total score and the CRIES-8 total score (r = 0.354, P < .01). CONCLUSIONS: The sleep-related difficulties occurring during COVID-19 outbreak may compound to increase the risk to develop post-traumatic stress disorder among Italian children.

Acute poisoning in children admitted to pediatric emergency department: a five-years retrospective analysis.

BACKGROUND AND AIM: to identify most frequent risk factors and to propose prevention strategies for the children admitted to Pediatric Emergency Department (PED) with acute poisoning. METHODS: We performed a retrospective study in a tertiary care hospital, describing the frequency and nature of pediatric poisoning, clinical management and outcome. RESULTS: We collected data of 436 children admitted for acute poisoning. The mean age was 30 months and 51.1% were male. Most poisoning incidents (90.1%) were unintentional and drug ingestion (39.4%) was the leading cause of poisoning. Acute poisoning happened at home in 83,7% of cases and the mother was the most frequent caregiver during the event in 61.5%. No died were reported. CONCLUSION: Our study showed that the two categories of patients at greatest risk for acute poisoning are children under 3 years and adolescents over 12 years. Adequate information campaigns about toxic substances are essential for children, adolescents and their parents.

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.

IBI Score to Improve Clinical Practice in Newborns and Infants ≤ 60 Days with Fever in the Emergency Department.

Fever is the most common problem of children admitted to emergency department (ED). The management of febrile patients ≤ 60 d old admitted to the Pediatric Emergency Department in the last 5 y was evaluated, applying the invasive bacterial infection (IBI) score proposed to evaluate the reliability and safety of this score in the authors' setting.Medical records of 280 patients with fever reported and/or detected in ED were retrospectively analyzed. A total of 166 patients were enrolled, whose average IBI score was 2.98 IBI score < 2 showed a sensitivity of 100.00% [95% CI (71.5-100.0)] and a specificity of 28.39% [95% CI (21.4-36.2)] compared to blood culture. IBI score can be a valid support to identify patients with low risk of invasive infection.

Iron-deficiency anaemia in childhood: a risk factor for severe venous thrombosis?

Iron deficiency anaemia is a common disorder in the paediatric age-group. The association between iron deficiency and venous thrombosis in children without an underlying illness is rare. Two cases are described. A 17-year-old girl had been taking oestrogen-progestogen therapy for contraception for about 2 years and developed a lower-limb deep vein thrombosis associated with pulmonary embolism. A 3-year-old girl was admitted to the paediatric emergency department with pallor, weakness and vomiting, and a cerebral CT showed a recent cerebral venous thrombosis. Both cases had severe iron-deficiency anaemia which increases a thrombotic tendency and could be a further crucial trigger of venous thrombosis in patients at low risk; therefore, in cases of unexplained thrombosis, it must always be considered to be a risk factor.Abbreviations APCR: activated protein C resistance; CMV: cytomegalovirus; CT: computerised tomography; CVST: cerebral venous sinus thrombosis; CVT: cerebral venous thrombosis; DVT: deep vein thrombosis; DOACs: direct oral anticoagulants; EBV: Epstein-Barr virus; ID: iron deficiency; IDA: iron deficiency anaemia; LMWH: low molecular weight heparin; PE: pulmonary embolism; RDW: red blood cell distribution width; VT: venous thrombosis.

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.