Children with medical complexity and pediatric palliative care: Data by a respiratory intermediate care unit.

Pediatric palliative care (PPC) is an active and total approach to the care of children with life-limiting conditions and their families. PPC programs provide ongoing treatment for children with medical complexity (CMC), many of whom will reach adulthood. Aim of the study was to describe a population of CMC attendingin six preselected months the Respiratory Intermediate Care Unit of a tertiary referral hospital for southern and central Italy. We enrolled all CMC patients admitted to our unit in six preselected months and registered pathologies and different categories of childhood diseases, devices and needs, hospitalization and home care plan. Among the 275 children admitted to our unit, 130 CMC were included. Median age was 9.9 (0.1-40.0) years. The main pathologies recorded were neuromuscular, neurological, respiratory, metabolic and malformative diseases, genetic syndromes and outcomes of prematurity. Comorbidity due to respiratory, digestive, neurological, cardiac and urological involvement was present in a high percentage of cases. Among our patients, only 46 were not carriers of any medical device. The average length of hospitalization was 7.0 (1.0-270.0) days with 2 (1.0-7.0) admissions per year per patient. Home care activation was not required for 47 out of 130 patients. Children eligible for PPC are increasing and their survival results in a rise of comorbidities and special needs demanding multilevel interventions. Respiratory symptoms are the most recurrent ones observed, thus requiring an expert in PPC with expertise in the respiratory field. Sharing data and knowledge of CMC needs may help improve care coordination.

E-cigarette or Vaping product use Associated Lung Injury (EVALI) in a 15 year old female patient - case report.

BACKGROUND: E-cigarettes are devices which allow to aerosolize liquids containing nicotine or other substances. Ever since they were released on the market in 2006, the number of users have been constantly increasing, especially among adolescents, ranging from 7,6% to 9,3% in the age group 18-24 years old from 2014 to 2019. Hand in hand with the spread of E-cigarettes many have been the efforts to understand their impact on health. EVALI (E-cigarette or Vaping product use Associated Lung Injury) is an emerging condition with a heterogeneous presentation with several reported cases worldwide. We mean to report a case of EVALI in a 15-year-old female Caucasian patient, who's currently attending her clinic follow-up at Bambino Gesù Pediatric Hospital in Rome. CASE PRESENTATION: The patient was admitted to the Emergency Room due to acute respiratory failure in November 2020. At admittance, she was severely dyspneic (HR 120 bpm, SatO2 75%). As she was hospitalized amid the COVID-19 pandemics, she underwent a nasopharyngeal swab for SARS-CoV2, which turned out negative, and a chest CT scan. Chest CT scan showed a central ground grass pattern with peripheral sparing. At the anamnestic recall, it was disclosed she was an e-cigarette smoker and occasional marijuana user. The microbiological work-up proved only positive for Rhinovirus. Her clinical and radiological case was discussed with our radiologist who suspected EVALI. She was assisted through HFNC, antibiotical therapy and corticosteroids with a dramatic recovery within the first 48 h. CONCLUSIONS: EVALI started being recognized a specifically nosological entity in summer 2019, with increasing cases being reported. No diagnostic criteria have been agreed upon yet, but its usual presentation includes respiratory, gastrointestinal and systemic symptoms of different degree and the diagnosis can be hypothesised in case the patient has an evocative clinical and radiological presentation and has been an E-cigarette smoker in previous 90 days. Due to the novelty of the condition and its heterogeneous presentation it is of interest to report the cases in which EVALI is identified to raise awareness about this emerging new-age disease.

How the Management of Children With Congenital Central Hypoventilation Syndrome Has Changed Over Time: Two Decades of Experience From an Italian Center.

Background: Congenital central hypoventilation syndrome (CCHS) is a rare disorder whose clinical phenotype is closely related to genotype. Methods: A retrospective analysis has been conducted on 22 patients with CCHS, who were referred to the Pediatric Pulmonology and Respiratory Intermediate Care Unit of Bambino Gesù Children's Hospital (Italy) for a multidisciplinary follow-up program between 2000 and 2020. Results: Apnea and cyanosis were the most frequent symptoms at onset (91%). Overall, 59% of patients required tracheostomy and invasive mechanical ventilation (IMV) in the first months of life. Thirty-two percent of patients had Hirschsprung disease (HSCR) that was associated with longer polyalanine repetitions or non-polyalanine repeat expansion mutations (NPARMs). Polyalanine repeat expansion mutations (PARMs) were more frequent and two novel NPARMs (c.780dupT and C.225-256delCT) were described in 14% of patients. Focal epilepsy was first described in 14% of patients and neurocognitive and neuromotor impairment involved 27% and 23% of children, respectively. Symptoms due to autonomic nervous system dysfunction/dysregulation (ANSD)-including strabismus (27%), dysphagia (27%), abnormal heart rhythm (10%), breath-holding spells (9%), and recurrent seizures due to hypoglycemia (9%)-were associated with an increased number of polyalanine repetitions of exon 3 or NPARMs of PHOX2B gene. Overall, the number of patients with moderate to severe phenotype initially treated with non-invasive ventilation (NIV) increased over time, and the decannulation program was concluded with 3 patients who started with IMV. Conclusions: Our study confirms that more severe phenotypes of CCHS are related to the number of polyalanine repetitions or to NPARMs. Although invasive ventilation is often required by patients with severe genotype/phenotype, gradual acquisition of specific skills in the management of patients with CCHS and technological improvements in mechanical ventilation allowed us to improve our therapeutic approach in this population.

All You Need Is Evidence: What We Know About Pneumonia in Children With Neuromuscular Diseases.

Neuromuscular diseases may involve all major respiratory muscles groups including inspiratory, expiratory, and bulbar muscles. Respiratory complications are the major cause of morbidity and mortality. Pneumonia represents a frequent cause of morbidity in children with neuromuscular disease. The aim of this review is to collect knowledge about pneumonia in children with neuromuscular diseases. Pneumonia usually follows viral respiratory infections of the upper respiratory tract, due to the combination of an increased amount of nasal and oral secretions and an impairment of the cough efficiency and of the clearance of secretions due to the muscle weakness, further compromised by the infection itself. The accumulation of bronchial secretions leads to atelectasis and promote bacterial infection. Moreover, dysfunction of swallowing mechanism exposes these children to the risk of developing aspiration pneumonia. However, etiology of viral and bacterial respiratory infection in these patients is still poorly studied.

Two novel mutations in exon 3 of PHOX2B gene: think about congenital central hypoventilation syndrome in patients with Hirschsprung disease.

BACKGROUND: Congenital central hypoventilation syndrome (CCHS) is characterized by alveolar hypoventilation increasing during sleep and affected patients are unable to perceive and respond to hypercarbia with increased ventilation and arousal during sleep. PHOX2B gene mutations are considered as responsible for CCHS. Most of patients with CCHS are heterozygous for polyalanine expansion mutations (PARMs) in exon 3, but 10% of patients with classic CCHS are heterozygous for non-polyalanine expansion mutations (NPARMs) of the PHOX2B gene. METHODS: Data are collected on 3 patients affected by CCHS who referred to the Paediatric Pulmonology Unit of Bambino Gesù Children's Hospital (Rome, Italy) for a multidisciplinary follow-up program between 2000 and 2017. RESULTS: We describe three cases of patients affected by CCHS for which two novel mutations on exon 3 of PHOX2B gene were detected. CONCLUSIONS: The description of these novel mutations and related clinical phenotypes allows to expand the knowledge into NPARM spectrum. Since the presence of Hirschsprung disease is related to NPARMs and the number of alanine repeats, we suggest performing CCHS genetic investigation and periodical assessment also in patients without a clear history of CCHS but affected by Hirschsprung disease. TRIAL REGISTRATION: Data are retrospectively collected.

Pleural effusion from intrathoracic migration of a ventriculo-peritoneal shunt catheter: pediatric case report and review of the literature.

BACKGROUND: Pleural effusion is a rare complication of ventriculo-peritoneal (VP) cerebrospinal fluid (CSF) shunting and its diagnosis is difficult in patients with neurological and consciousness impairment. CASE REPORT: Herein we report the case of a child affected by Pfeiffer syndrome and hydrocephalus, shunted at the age of 3 months, who developed acute respiratory failure due to a right-sided pleural effusion 2 years later. Plain chest radiographs and computed tomography (CT) showed the intrathoracic migration of the right VP shunt abdominal tip. Beta-2 transferrin, a marker for CSF, was found in the pleural fluid and the hypothesis of a CSF hydrothorax was confirmed. Effusion was treated with a thoracentesis. Seven days after, the right VP shunt was revised; a ventriculo-atrial (VA) shunt was also placed on the left side to serve as the main CSF shunt and to prevent the recurrence of hydrothorax. We review the pediatric cases of CSF hydrothorax reported in the literature and discuss the mechanisms underlying this complication together with the possible treatments. CONCLUSION: Pleural effusion due to VP shunt insertion is a rare and potentially life-threatening condition that should be suspected in any patient with a VP shunt and respiratory failure. Signs of hydrothorax may moreover represent the only clinical evidence of a shunt-related complication in case of neurologically severely compromised patients in which neurologic examination cannot help to make a diagnosis.

Anaphylactic shock with methylprednisolone sodium succinate in a child with short bowel syndrome and cow's milk allergy.

BACKGROUND: Medications with methyl-prednisolone sodium succinate containing lactose, which potentially contains traces of cow's milk proteins (CMP), could cause allergic reactions or compromise treatment of acute allergic reactions in sensitized patients. CASE PRESENTATION: We describe the unusual case of a one-year-old child affected by short bowel syndrome and history of severe cow's milk allergy (CMA) and anaphylactic reaction due to intravenous administration of methyl-prednisolone sodium succinate (Solu-Medrol 40 mg, Pfizer). He was admitted to our hospital for severe respiratory failure and was initially treated with methyl-prednisolone (Urbason 40 mg, Sanofi Aventis), then with methyl-prednisolone sodium succinate (Solu-Medrol 40 mg, Pfizer). After the intravenous administration of second steroid, immediate anaphylaxis was recorded and treatment was stopped. Antihistamine and epinephrine were required and symptom resolution occurred. CONCLUSION: Children who are highly sensitive to milk may have severe allergic reactions also after exposure to CMP through a different administration route than the oral one. Patients who have food allergies need to pay particular attention to the prescription of drugs and their formulation.

Surfactant Protein C-associated interstitial lung disease; three different phenotypes of the same SFTPC mutation.

BACKGROUND: Monoallelic mutations of the Surfactant Protein C gene (SFTPC) are associated with Interstitial Lung Disease in children. I73T is the most common mutation, accounting for 30 % of all cases reported. CASE PRESENTATION: We describe three patients carrying the same I73T SPC mutation with very different phenotypes, clinical course (ranging from mild respiratory symptoms to death for respiratory failure) and outcome. CONCLUSIONS: The disease mechanisms associated with SP-C mutations suggest that the combination of individual genetic background and environmental factors contribute largely to the wide variability of clinical expression. Infants, children and adults with ILD of unknown etiology should be investigated for SP-C genetic abnormalities.

Respiratory insufficiency in a newborn with congenital hypothyroidism due to a new mutation of TTF-1/NKX2.1 gene.

NK2 homeobox-1 (NKX2.1) gene encoding the thyroid transcription factor-1 (TTF-1) plays a critical role in lung, thyroid, and central nervous system morphogenesis and function; mutations cause a rare form of progressive respiratory failure associated with alterations of surfactant synthesis, composition, and homeostasis. Molecular mechanisms are heterogeneous and poorly explored. A 28 days old male, soon after birth, presented respiratory failure requiring oxygen treatment at FiO2 27%, prolonged for 2 weeks. Routine neonatal screenings detected a high thyroid stimulating hormone concentration. On day 27 congenital hypothyroidism was confirmed and substitutive treatment was begun. Since the persistence of respiratory symptoms sweat test, CFTR mutation, lymphocyte subpopulations, and sputum cultures were tested, resulting negative. Brain and cardiac defects were also ruled out. Bronchoscopy and BAL analysis were normal. Computed tomography showed bilateral multiple ground glass attenuation, consolidative areas and diffuse bronchial wall thickening. Based on the severity of symptoms, the exclusion of other causes of respiratory disease and the CT findings of interstitial lung disease, we investigated genes affecting the surfactant homeostasis. Sequencing analysis of the three exons of the TTF1 revealed a heterozygous mutation c.334G > T that results in the replacement of glycine in position 112 with a stop codon, generating a nonsense protein that lacks the correct transactivation domain in the C-terminal region. Genetic analysis of the family showed that the father, who was asymptomatic, carried the mutation. Screening for TTF-1 deletions or mutations should always be considered in children with congenital hypothyroidism and an unexplained neonatal respiratory distress or neurodevelopmental deficits.

Preliminary data on monosymptomatic nocturnal enuresis in children and adolescents with type 1 diabetes.

OBJECTIVE: To evaluate the prevalence of monosymptomatic nocturnal enuresis (MNE) in a group of children and adolescents prior to the onset of type 1 diabetes (Dt1). MATERIAL AND METHODS: We considered 88 patients with Dt1 with a mean age of 15.2 years over a period of 3 years. All patients were investigated by means of a questionnaire about the occurrence of MNE prior to the onset of Dt1. Each patient had normal urinalysis results, with no glycosuria, a normal urinary flow rate and no day-time symptoms such as urge incontinence or urgency. RESULTS: We found that 24/88 patients (27.2%) were bedwetters before the onset of Dt1. After beginning insulin treatment, 7/24 bedwetters (29.2%) kept presenting MNE. In total, 7 of the initial 88 patients (7.9%) displayed persistent features of MNE. CONCLUSIONS: The occurrence of MNE may overlap with symptoms of Dt1 but requires specific medical attention as a separate entity due to its possible persistence even when Dt1 has been controlled by insulin treatment.

Helicobacter pylori eradication rate and glycemic control in young patients with type 1 diabetes.

OBJECTIVES: Eradication of Helicobacter pylori is more difficult in adult patients with diabetes than in patients with dyspepsia. It has also been suggested that eradication of H. pylori in children with type 1 diabetes mellitus improves their metabolic control. The aim of the current study was to assess the eradication rate of a standard triple therapy and its effects on glycemic control in young patients with type 1 diabetes. METHODS: The authors enrolled 29 type 1 diabetic patients with H. pylori, 29 type 1 diabetic patients without H. pylori, and 29 dyspeptic children with H. pylori. Groups were matched for gender and age and had similar geographical origin and socioeconomic status. H.pylori status was investigated before and 6 weeks after therapy by C-urea breath test. All enrolled patients with H. pylori were prescribed a standard triple therapy for eradicating H. pylori. Glycosylated hemoglobin A and daily insulin requirement were evaluated at enrollment and 6 months later in all patients with diabetes. The prevalence of the most common gastrointestinal symptoms also was investigated by means of a questionnaire in all subjects at enrollment and 6 months later. RESULTS: Eradication of H. pylori was similar in patients with diabetes (24/29) and those with dyspepsia (23/29) (83%v 79%; P = NS). No difference in metabolic control was observed before or after antibiotic treatment in the patients who experienced H. pylori eradication. No difference in glycemic control was observed after 6 months of follow-up. CONCLUSIONS: The eradication rate of H. pylori infection was similar for young patients with type 1 diabetes and those with dyspepsia and did not improve metabolic control in a short-term follow-up.

Helicobacter pylori, gastrointestinal symptoms, and metabolic control in young type 1 diabetes mellitus patients.

OBJECTIVE: The role of Helicobacter pylori infection in metabolic control and gastrointestinal symptoms in type 1 diabetes mellitus (DM1) patients has been debated. The aim of this study was to investigate the prevalence of H pylori, of the more cytotoxic Cag-A-positive strains, and the effects of infection on gastrointestinal symptoms and metabolic control in young DM1 patients. Research Design and Methods. H pylori infection was investigated by using the 13C-urea breath test in 121 DM1 patients (65 males, 56 females; mean age: 15 +/- 6 years) and 147 matched controls. In positive patients, an assay for specific immunoglobulin G against Cag-A was performed. Glycosylated hemoglobin A, daily insulin requirement, and duration of illness were established; a questionnaire concerning the presence of dyspeptic symptoms was administered. RESULTS: No difference in H pylori infection rate between patients and controls was observed. Thirty-four (28.1%) of 121 patients and 43 (29.25%) of 147 controls were infected. Twenty-one patients and 24 controls were positive for Cag-A. Glycosylated hemoglobin A, daily insulin requirement, and duration of illness were not affected by infection nor by Cag-A status. Among gastrointestinal symptoms, only halitosis was related to H pylori infection, but this association disappeared after correction for age. Positive patients with halitosis showed a worse glycemic control than uninfected patients with halitosis. CONCLUSIONS: H pylori infection and Cag-A-positive strains do not affect metabolic control in DM1 patients. With regard to gastrointestinal symptoms studied, H pylori infection, when present in participants with halitosis, seems to predict a worse metabolic control than in H pylori-negative patients with halitosis.