Critical care of severe bronchiolitis during shortage of ICU resources.

Large seasonal outbreaks of bronchiolitis put pressure on healthcare systems and particularly on intensive care units (ICUs). ICU admission is necessary to provide respiratory support to the severest cases, otherwise bronchiolitis can result in substantial mortality. ICU resources are often insufficient and there is scant evidence to guide the ICU clinical management. Most available studies do not cover the ICU-admitted cases and do not consider the associated public health issues. We review this topic through a multidisciplinary approach from both the clinical and public health perspectives, with an analysis based on pathophysiology and cost-effectiveness. We suggest ways to optimise respiratory care, minimise ICU stay, "protect" ICU beds and, whenever possible, make them available for other critically ill children. We also provide guidance on how to prepare ICUs to work under stressful conditions due to outbreaks and to reduce the risk of nosocomial cross-contamination, particularly in ICUs caring for high-risk children. Funding: None.

Complicated Falciparum Malarial ARDS Requiring Noninvasive Support.

Severe plasmodium falciparum infection can induce respiratory distress and clinical ARDS in children, requiring intensive care admission and respiratory support. We present 3 cases of imported malarial acute respiratory distress syndrome requiring noninvasive ventilation in the pediatric intensive care unit, in the absence of any cerebral involvement. Radiological features and their relationship with severe hematological complications are also illustrated.

Hyperemia in head injury: can transcranial doppler help to personalize therapies for intracranial hypertension?

Introduction: An increase in cerebral blood flow is frequent after traumatic brain injury (TBI) and can lead to brain swelling and refractory intracranial hypertension. We hypothesized that Transcranial EcoDoppler (TCD) monitoring could be useful to detect the cause of intracranial hypertension in these patients. Our main objective was to investigate if the increase of velocity in the middle cerebral artery (MCA) on TCD could be associated with intracranial hypertension. Methods: We retrospectively studied TBI patients consecutively monitored with TCD. Hyperemia was defined as MCA mean velocity higher than 80 cm/s. Intracranial hypertension was considered when hyperosmolar therapy, hyperventilation, or deep sedation was used. Results: We found hyperemia in 40 patients out of 118 (33.9%). On average, it started at day 2.1 ± 0.9 from admission and significantly increased (MCA velocity at day 1: 74 ± 25 cm/s vs. 109 ± 36 cm/s at day 4; p < 0.001). Intracranial hypertension was significantly associated with hyperemia, occurring in 92.5% of hyperemic and 51.3% of non-hyperemic patients (p < 0.001). Moreover, we found that hyperemia preceded severe intracranial hypertension (p < 0.0001). In a logistic regression model, hyperemia was the only variable significantly correlated with intracranial hypertension (OR 10.64; p < 0.001). Discussion: Hyperemia was frequent in our population of TBI patients and preceded intracranial hypertension. TCD monitoring, if performed on a daily regular basis, can be a useful method to detect this phenomenon and to guide the therapy. It could be a tool for a cause-oriented therapy of intracranial hypertension.

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.

Retrospective Study on Staphylococcus aureus Resistance Profile and Antibiotic Use in a Pediatric Population.

The growing phenomenon of antibiotic resistance and the presence of limited data concerning the pediatric area prompted us to focus on Staphylococcus aureus infection in this study, its antibiotic resistance profile, and the therapeutic management of affected children. We conducted a retrospective study by collecting clinical data on infants and children with antibiogram-associated S. aureus infection. We enrolled 1210 patients with a mean age of 0.9 years. We analyzed the resistance patterns and found 61.5% resistance to oxacillin, 58.4% resistance to cephalosporins, 41.6% resistance to aminoglycosides, and 38.3% resistance to fluoroquinolones. Importantly, we found no resistance to glycopeptides, a key antibiotic for MRSA infections whose resistance is increasing worldwide. We also found that the main risk factors associated with antibiotic resistance are being aged between 0 and 28 days, the presence of devices, and comorbidities. Antibiotic resistance is a growing concern; knowing the resistance profiles makes it possible to better target the therapy; however, it is important to use antibiotics according to the principles of antibiotic stewardship to limit their spread.

A theory-based and data-driven approach to promoting physical activity through message-based interventions.

Objective: We investigated how physical activity can be effectively promoted with a message-based intervention, by combining the explanatory power of theory-based structural equation modeling with the predictive power of data-driven artificial intelligence. Methods: A sample of 564 participants took part in a two-week message intervention via a mobile app. We measured participants' regulatory focus, attitude, perceived behavioral control, social norm, and intention to engage in physical activity. We then randomly assigned participants to four message conditions (gain, non-loss, non-gain, loss). After the intervention ended, we measured emotions triggered by the messages, involvement, deep processing, and any change in intention to engage in physical activity. Results: Data analysis confirmed the soundness of our theory-based structural equation model (SEM) and how the emotions triggered by the messages mediated the influence of regulatory focus on involvement, deep processing of the messages, and intention. We then developed a Dynamic Bayesian Network (DBN) that incorporated the SEM model and the message frame intervention as a structural backbone to obtain the best combination of in-sample explanatory power and out-of-sample predictive power. Using a Deep Reinforcement Learning (DRL) approach, we then developed an automated, fast-profiling strategy to quickly select the best message strategy, based on the characteristics of each potential respondent. Finally, the fast-profiling method was integrated into an AI-based chatbot. Conclusion: Combining the explanatory power of theory-driven structural equation modeling with the predictive power of data-driven artificial intelligence is a promising strategy to effectively promote physical activity with message-based interventions.

Nasal polyposis in pediatric patients with Cornelia de Lange syndrome: endoscopic diagnosis, treatment and follow up in two case reports.

BACKGROUND: Cornelia de Lange syndrome is a rare genetic disease with otolaryngological involvement. The classic phenotype is characterized by distinctive facial features, intellectual disability, growth delay, hirsutism, and upper-limb reduction. Nasal polyposis was previously reported in association with chronic rhinosinusitis, however data about prevalence, diagnosis, treatment and prognosis are lacking for this cohort of patients, affected by rare disease. CASE PRESENTATION: We describe the whole diagnostic and therapeutic workflow of nasal polyps in two pediatric patients with Cornelia de Lange, successfully diagnosed and treated by nasal endoscopy. CONCLUSION: Our report confirm that nasal endoscopy is a safe and useful tool in the diagnosis, treatment and follow-up of nasal polyps, even in Cornelia de Lange syndrome pediatric patients. We want to increase the alert for the detection of nasal polyps in patients with Cornelia de Lange syndrome since pediatric age. We recommend endoscopy in all patients with Cornelia de Lange syndrome and symptoms of chronic nasal obstruction and/or OSAS. Multidisciplinary team and sedation service could be useful in the management of Cornelia de Lange syndrome patients with airway obstruction symptoms and sleep disturbance when severe intellectual disability, autism or psychiatric findings are present.

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.

Comparative evaluation of three total full-face masks for delivering Non-Invasive Positive Pressure Ventilation (NPPV): a bench study.

Historically, the oro-nasal mask has been the preferred interface to deliver Non-Invasive Positive Pressure Ventilation (NPPV) in critically ill patients. To overcome the problems related to air leaks and discomfort, Total Full-face masks have been designed. No study has comparatively evaluated the performance of the total Full-face masks available.The aim of this bench study was to evaluate the influence of three largely diffuse models of total Full -face masks on patient-ventilator synchrony and performance during pressure support ventilation. NPPV was applied to a mannequin, connected to an active test lung through three largely diffuse Full-face masks: Dimar Full-face mask (DFFM), Performax Full-face mask (RFFM) and Pulmodyne Full-face mask (PFFM).The performance analysis showed that the ΔPtrigger was significantly lower with PFFM (p < 0.05) at 20 breaths/min (RRsim) at both pressure support (iPS) levels applied, while, at RRsim 30, DFFM had the longest ΔPtrigger compared to the other 2 total full face masks (p < 0.05). At all ventilator settings, the PTP200 was significantly shorter with DFFM than with the other two total full-face masks (p < 0.05). In terms of PTP500 ideal index (%), we did not observe significant differences between the interfaces tested.The PFFM demonstrated the best performance and synchrony at low respiratory rates, but when the respiratory rate increased, no difference between all tested total full-face masks was reported.

Successful stem cell collection for atypical teratoid rhabdoid tumor in an extremely low-body weight child: A case report.

The use of peripheral blood hematopoietic stem cells for bone marrow reconstitution after myeloablative therapy is well established in children with malignant disorders. However, the peripheral blood hematopoietic stem cells collection in very low-body weight (≤10 kg) children remains a significant challenge because of technical and clinical issues. A male newborn affected by atypical teratoid rhabdoid tumor, diagnosed prenatally, received two cycles of chemotherapy following surgical resection. After an interdisciplinary discussion, it was decided to intensify the treatment with high-dose chemotherapy followed by autologous stem cell transplantation. After 7 days of G-CSF administration the patient underwent hematopoietic progenitor cells-apheresis collection. The procedure was performed in the pediatric intensive care unit, using two central venous catheters and Spectra Optia device. The cell collection procedure was completed in 200 min, during which time 3.9 total blood volumes were processed. During apheresis we did not observe electrolyte alterations. No adverse events were recorded during or immediately following the cell collection procedure. Our report describes the feasibility of performing large volume leukapheresis without complications in an extremely low-body weight patient weighing 4.5 kg using the Spectra Optia apheresis device. No catheter-related problems occurred, and apheresis was completed without any adverse event. In conclusion, we believe that very low-body weight pediatric patients need a multidisciplinary approach to manage central venous access, hemodynamic monitoring, cell collection, prevention of metabolic complications to improve safety, feasibility, and efficiency of stem cell collection procedures.

Type I spinal muscular atrophy patients treated with nusinersen: 4-year follow-up of motor, respiratory and bulbar function.

BACKGROUND: We report the 4-year follow-up in type I patients treated with nusinersen and the changes in motor, respiratory and bulbar function in relation to subtype, age and SMN2 copy number. METHODS: The study included SMA 1 patients with at least one assessment after 12, 24 and 48 months from the first dose of nusinersen. The assessments used were Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) and the Hammersmith Infant Neurological Examination (HINE-II). RESULTS: Forty-eight patients, with ages ranging from 7 days to 12 years (mean 3.3 years, SD 3.6 years) were included in the study. The CHOP INTEND and HINE-II scores significantly increased between baseline and 48 months (p < 0.001). When age at starting treatment subgroups (<210 days, <2 years, 2-4 years, 5-11 years, ≥12 years) were considered, the CHOP INTEND increased significantly in patients younger than 4 years at treatment, while the HINE-2 increased significantly in patients younger than 2 years at treatment. In a mixed-model analysis, age, nutritional and respiratory status were predictive of changes on both scales while SMN2 copy number and decimal classification were not. CONCLUSIONS: Our results confirm the safety profile previously reported and support the durability of the efficacy of nusinersen at 4 years with an overall stability or mild improvement and no evidence of deterioration over a long period of time.

Multisystemic involvement of post-traumatic fat embolism at a Pediatric Trauma Center: a clinical series and literature review.

Post-traumatic fat embolism syndrome (FES) is a severe complication consequent to bone fractures. The authors describe its clinical features and management in a population of teenagers by detailing demographics, organ involvement, laboratory, and imaging findings, as well as outcome. Moreover, a systematic review of pediatric published case reports of post-traumatic FES is provided. First, a series of eight episodes of post-traumatic FES that occurred in seven patients (median age 16.0 years, IQR 16.0-17.5) admitted to a pediatric intensive care unit (PICU) in an 8-year period was analyzed through a retrospective chart review. Secondly, a systematic research was performed on PUBMED database. Trauma patients ≤ 18 years without comorbidities in a 20-year period (2002-2022) were included in the review. Neurological impairment was present in five out of seven patients, and a patent foramen ovale was found in four cases. Hemodynamic instability requiring vasoactive drugs was recorded in four patients. A severe form of acute respiratory distress syndrome (ARDS) occurred in five cases, with the evidence of hemorrhagic alveolitis in three of them. In the literature review, eighteen cases were examined. Most cases refer to adolescents (median age 17.0 years). More than half of patients experienced two or more long bone fractures (median: 2 fractures). Both respiratory and neurological impairment were common (77.8% and 83.3%, respectively). 88.9% of patients underwent invasive mechanical ventilation and 33.3% of them required vasoactive drugs support. Neurological sequelae were reported in 22.2% of patients. CONCLUSION: Post-traumatic FES is an uncommon multi-faceted condition even in pediatric trauma patients, requiring a high level of suspicion. Prognosis of patients who receive prompt support in an intensive care setting is generally favorable. WHAT IS KNOWN: •Post-traumatic fat embolism syndrome is a severe condition complicating long bone or pelvic fractures. •Little is known about clinical features and management in pediatric age. WHAT IS NEW: •Post-traumatic fat embolism syndrome can cause multiple organ failure, often requiring an intensive care management. •Prompt supportive care contributes to a favorable prognosis.

Needleless inhaled anesthesia with sevoflurane: Advantages of a simplified approach for children with spinal muscular atrophy undergoing intrathecal administration of nusinersen.

BACKGROUND: Intrathecal nusinersen administration, a fundamental step in the treatment of spinal muscular atrophy, is challenging in children. AIMS: This retrospective monocentric analysis of prospectively collected data evaluated the feasibility of needleless general anesthesia exclusively with sevoflurane, without imaging guidance, for children undergoing nusinersen administration in a 24-month period. METHODS: Clinical data included demographics, type of spinal muscular atrophy, presence and severity of scoliosis. Primary outcome was defined by the number of predefined sentinel adverse events related to anesthesia. Secondary outcomes were assessed by duration of the procedure, number of lumbar puncture attempts, and number of failures. Other measures included number and type of moderate, minor and minimal adverse events, as well as number and type of puncture-related adverse events. RESULTS: 116 patients (mean age: 8.7 (SD 6.9) years; with scoliosis: 49.1%) underwent 250 lumbar punctures; two cases of prolonged desaturation, considered as sentinel adverse events, (0.8%) were recorded during anesthesia (primary outcome). None of the patients underwent orotracheal intubation nor required an unplanned admission in the Pediatric Intensive Care Unit. No patient required an unplanned or prolonged hospitalization after the procedure. Mean number of puncture attempts was 1.6 (SD 1.3), and mean duration of the procedure was 14.1 (SD 8.3) minutes. No failure in the drug administration occurred (secondary outcomes). CONCLUSION: In this single-center experience, needleless general anesthesia with inhaled sevoflurane without imaging guidance has been shown to be feasible for children with spinal muscular atrophy undergoing lumbar puncture for nusinersen administration.

Ultrasound-assessed lung aeration correlates with respiratory system compliance in adults and neonates with acute hypoxemic restrictive respiratory failure: an observational prospective study.

BACKGROUND: Lung ultrasound allows lung aeration to be assessed through dedicated lung ultrasound scores (LUS). Despite LUS have been validated using several techniques, scanty data exist about the relationships between LUS and compliance of the respiratory system (Crs) in restrictive respiratory failure. Aim of this study was to investigate the relationship between LUS and Crs in neonates and adults affected by acute hypoxemic restrictive respiratory failure, as well as the effect of patients' age on this relationship. METHODS: Observational, cross-sectional, international, patho-physiology, bi-center study recruiting invasively ventilated, adults and neonates with acute respiratory distress syndrome (ARDS), neonatal ARDS (NARDS) or respiratory distress syndrome (RDS) due to primary surfactant deficiency. Subjects without lung disease (NLD) and ventilated for extra-pulmonary conditions were recruited as controls. LUS, Crs and resistances (Rrs) of the respiratory system were measured within 1 h from each other. RESULTS: Forty adults and fifty-six neonates were recruited. LUS was higher in ARDS, NARDS and RDS and lower in control subjects (overall p < 0.001), while Crs was lower in ARDS, NARDS and RDS and higher in control subjects (overall p < 0.001), without differences between adults and neonates. LUS and Crs were correlated in adults [r = - 0.86 (95% CI - 0.93; - 0.76), p < 0.001] and neonates [r = - 0.76 (95% CI - 0.85; - 0.62), p < 0.001]. Correlations remained significant among subgroups with different causes of respiratory failure; LUS and Rrs were not correlated. Multivariate analyses confirmed the association between LUS and Crs both in adults [B = - 2.8 (95% CI - 4.9; - 0.6), p = 0.012] and neonates [B = - 0.045 (95% CI - 0.07; - 0.02), p = 0.001]. CONCLUSIONS: Lung aeration and compliance of the respiratory system are significantly and inversely correlated irrespective of patients' age. A restrictive respiratory failure has the same ultrasound appearance and mechanical characteristics in adults and neonates.

Influence of total face masks design and circuit on synchrony and performance during pressure support ventilation: A bench study.

BACKGROUND: Few studies investigated the influence of the circuit applied during non-invasive ventilation (NIV) with a total face mask. The aim of this bench study was to evaluate the effects of separated inflow and outflow ports in a total face mask on patient ventilator interaction and performance during NIV through a total face mask. METHODS: A mannequin was connected to an active lung simulator. NIV was applied both via a standard total face mask (STFM) with a Y-piece connector for inflow/outflow gases and a modified total face mask (MTFM) with 2 different connectors for inflow and outflow gases. RESULTS: The MTFM showed both a significantly better patient-ventilator interaction and a significantly higher performance. The MTFM showed a significantly lower Δtrigger compared to STFM (p<0.01) and shorter value of PTPtrigger during all ventilator setting tested (p < 0.01). Significant differences in PTP 200, PTP 300, and PTP 500 were observed between the MTFM and STFM (p < 0.01) in all conditions tested. Concerning PTP 500 ideal index, in all the conditions tested, the MTFM presented higher values compared to STFM, although those differences were not statistically significant. At both RRsim and ventilator settings tested, the MTFM showed a significantly shorter Delaytrinsp and Delaytrexp compared to STFM (p < 0.01). At both RRsim tested and both ventilator settings, the MTFM showed a significantly longer Timesync compared to STFM (p < 0.01). CONCLUSIONS: The MTFM showed a significantly better patient ventilator interaction and a better ventilator performance, suggesting that this kind of total face mask design should be preferred in clinical practice.