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Background: Efficacy and safety of onasemnogene abeparvovec (OA) for Spinal Muscular Atrophy infants under 7 months and <8.5 kg has been reported in clinical trials. This study examines efficacy and safety predictors in a wide age (22 days–72 months) and weight (3.2–17 kg) range, also including patients previously treated with other drugs. Methods: 46 patients were treated for 12 months between January 2020 and March 2022. Safety profile was also available for another 21 patients with at least 6 month follow-up after OA infusion. 19/67 were treatment naïve when treated with OA. Motor function was measured with the CHOP-INTEND. Findings: CHOP-INTEND changes varied among age groups. Baseline score and age at OA treatment best predicted changes. A mixed model post-hoc analysis showed that in patients treated before the age of 24 months the CHOP-INTEND changes were already significant 3 months after OA while in those treated after the age of 24 months the difference was only significant 12 months after OA. Adverse events occurred in 51/67. The risk for elevated transaminases serum levels was higher in older patients. This was also true for weight and for pre-treatment with nusinersen when analysed individually. A binomial negative regression analysis showed that only age at OA treatment had a significant effect on the risk of elevated transaminases. Interpretation: Our paper describes OA 12-month follow-up showing efficacy across various age and weight groups not targeted by clinical trials. The study identifies prognostic factors for safety and efficacy in treatment selection. Funding: None.

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.

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 ultra

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Effective recommendations on healthy food choice need to be personalized and sent out on a large scale. In this paper, we present a model of automatic message selection tailored on the characteristics of the recipient and focused on the reduction of red meat consumption. This model is obtained through the collaboration between social psychologists and artificial intelligence experts. Starting from selected psychosocial models on food choices and the framing effects of recommendation messages, we involved a sample of Italian participants in an experiment in which they: (a) filled out a first questionnaire, which was aimed at detecting the psychosocial antecedents of the intention to eat red/processed meat; (b) read messages differing as to the framing of the hypothetical consequences of reducing (gain, non-loss) versus not reducing (non-gain, loss) red/processed meat consumption; (c) filled out a second questionnaire, which was aimed at detecting participants’ reaction to the messages, as well as any changes in their intention to consume red/processed meat. Data collected were then employed to learn both the structure and the parameters of a Graphical Causal Model (GCM) based on a Dynamic Bayesian Network (DBN), aimed to predicting the potential effects of message delivery from the observation of the psychosocial antecedents. Such probabilistic predictor is intended as the basis for developing automated interactions strategies using Deep Reinforcement Learning (DRL) techniques. Discussion focuses on how to develop automatic interaction strategies able to foster mindful eating, thanks to (a) considering the psychosocial characteristics of the people involved; (b) sending messages tailored on these characteristics; (c) adapting interaction strategies according to people’s reactions.

Objective: To determine whether non-invasive ventilation (NIV) can avoid the need for tracheal intubation and/or reduce the duration of invasive ventilation (IMV) in previously intubated patients admitted to the pediatric intensive care unit (PICU) and developing acute hypoxemic respiratory failure (AHRF) after major traumatic injury. Study Design: A single center observational cohort study. Setting: Pediatric ICU in a University Hospital (tertiary referral Pediatric Trauma Centre) Population: During the 48-month study period, 276 patients (median age 6.4 years) with trauma were admitted to PICU; among 86 of them, who suffered from AHRF and received ventilation (IMV and/or NIV) for more than 12 hrs, 32 patients (median age 8.5 years) were treated with NIV. Inclusion/Exclusion Criteria: Inclusion criteria: at least 12 hours of NIV; exclusion criteria: patients with facial trauma or congenital malformations; patients receiving IMV <12 hours or perioperative ventilation. Measurements and Results: Among NIV patients, 27 (84,3%) were previously on IMV, while 5 (15,6%) could be managed exclusively with NIV. In patients with post-extubation respiratory distress, NIV was successful in 88.4% of cases. Before starting NIV, P/F ratio was 242.7 ± 71. After 8 hours of NIV treatment, a significant oxygenation improvement (PaO2/FiO2 = 354.3 ± 81; p = 0.0002) was found, with no significant changes in carbon dioxide levels. A trend toward increasing ventilation-free time has been evidenced; NIV resulted feasible and generally well tolerated. Conclusions: AHRF in trauma patients is multifactorial and may be due to many reasons, such as lung contusion, aspiration of blood or gastric contents. Systemic inflammatory response and transfusions may also contribute to hypoxia. Our pilot study strongly suggests that NIV can be applied in post-traumatic AHRF: it may successfully reduce the time of both invasive ventilation and deep sedation. Further data from controlled studies are needed

Background: Pediatric ARDS still represents a difficult challenge in Pediatric Intensive Care Units (PICU). Among different treatments proposed, exogenous surfactant showed conflicting results. Aim of this multicenter retrospective observational study was to evaluate whether poractant alfa use in pediatric ARDS might improve gas exchange in children less than 2 years old, according to a shared protocol. Methods: The study was carried out in fourteen Italian PICUs after dissemination of a standardized protocol for surfactant administration within the Italian PICU network. The protocol provides the administration of surfactant (50 mg/kg) divided in two doses: the first dose is used as a bronchoalveolar lavage while the second as supplementation. Blood gas exchange variations before and after surfactant use were recorded. Results: Sixty-nine children, age 0-24 months, affected by Acute Respiratory Distress Syndrome treated with exogenous porcine surfactant were enrolled. Data collection consisted of patient demographics, respiratory variables and arterial blood gas analysis. The most frequent reasons for PICU admission were acute respiratory failure, mainly bronchiolitis and pneumonia, and septic shock. Fifty-four children (78.3%) had severe ARDS (define by oxygen arterial pressure and inspired oxygen fraction ratio (P/F) < 100), 15 (21.7%) had moderate ARDS (100 < P/F < 200). PO2, P/F, Oxygenation Index (OI) and pH showed a significant improvement after surfactant use with respect to baseline (p < 0.001 at each included time-point for each parameter). No significant difference in blood gas variations were observed among four different subgroups of diseases (bronchiolitis, pneumonia, septic shock and others). Overall, 11 children died (15.9%) and among these, 10 (90.9%) had complex chronic conditions. Two children (18.2%) died while being treated with Extracorporeal Membrane Oxygenation (ECMO). Mortality for severe pARDS was 20.4%. Conclusion: The use of po

Previous research has shown that sending personalized messages consistent with the recipient's psychological profile is essential to activate the change toward a healthy lifestyle. In this paper we present an example of how artificial intelligence can support psychology in this process, illustrating the development of a probabilistic predictor in the form of a Dynamic Bayesian Network (DBN). The predictor regards the change in the intention to do home-based physical activity after message exposure. The data used to construct the predictor are those of a study on the effects of framing in communication to promote physical activity at home during the Covid-19 lockdown. The theoretical reference is that of psychosocial research on the effects of framing, according to which similar communicative contents formulated in different ways can be differently effective depending on the characteristics of the recipient. Study participants completed a first questionnaire aimed at measuring the psychosocial dimensions involved in doing physical activity at home. Next, they read recommendation messages formulated with one of four different frames (gain, non-loss, non-gain, and loss). Finally, they completed a second questionnaire measuring their perception of the messages and again the intention to exercise at home. The collected data were analyzed to elicit a DBN, i.e., a probabilistic structure representing the interrelationships between all the dimensions considered in the study. The adopted procedure was aimed to achieve a good balance between explainability and predictivity. The elicited DBN was found to be consistent with the psychosocial theories assumed as reference and able to predict the effectiveness of the different messages starting from the relevant psychosocial dimensions of the recipients. In the next steps of our project, the DBN will form the basis for the training of a Deep Reinforcement Learning (DRL) system for the synthesis of automatic interaction strategies.

To illustrate our experience with two cases of neonatal life-threatening hyperkalemia during therapeutic hypothermia (TH) despite a normal acid-base status, urine output, and preserved renal function. Clinical cases are presented from Pediatric Intensive Care Unit (PICU) admission to the onset of the hyperkalemia, with related complications and after resolution. Similar cases were not retrieved from a critical review of pertinent literature. Severe hyperkalemia pathophysiology and risk factors have been debated. Two full-term adequate for weight female neonates were admitted to PICU because of perinatal asphyxia who underwent TH. Prenatal history was completely uneventful, nor hereditary genetic conditions were reported; moreover, long-term follow-up ruled out any metabolic or renal disease. Despite an accurate evaluation of previous clinical series and literature on TH and perinatal asphyxia, these hyperkalemic episodes remain unexplained. The hypoxic-ischemic insult may affect multiple organs, mainly central nervous system, heart, lung, and kidneys; acute muscle breakdown and consequent rising of myoglobin may also have a precipitating role in acute kidney failure (AKF) and hyperkalemia. Electrolyte imbalance is a possible finding as a consequence of combined cell injury and AKF. In contrast, an isolated severe hyperkalemia is exceedingly rare in nonoliguric neonates.

Background: Myocardial bridging is largely considered to be a benign, symptomless congenital anomaly of the coronary arteries in which the intramyocardial coronary course is partially ‘tunnelled’ and leads to vessel compression during ventricular systole. There are few data regarding children. Objective: To report on myocardial bridging observed in children seeking medical help in the paediatric emergency room. Case presentation: A series of four children aged 6–13 years with symptomatic myocardial bridging but no other underlying cardiac abnormalities is reported. They were admitted to the paediatric emergency department during 2013–2016, three with chest pain after physical activity and one with septic shock. Results: Heart computed tomography scan in the first three demonstrated myocardial bridging of the left anterior descendent coronary artery’s branches; their 2-year follow-up was uneventful. The fourth patient presented with ventricular fibrillation 24 hours after admission and at autopsy there was an intramyocardial tract 4 cm long on the left anterior descendent coronary artery. Conclusions: This case series demonstrates that myocardial bridging can be symptomatic in children with no underlying cardiac disorders and should be included in the differential diagnosis of exertional chest pain and/or arrhythmias. Abbreviations: CRP, C-reactive protein; CT, computed tomography; D1, diagonal 1 artery; ECG, electrocardiogram; ED, emergency department; KD, Kawasaki disease; LAD, left anterior descending coronary artery; MB, myocardial bridging; RI, ramus intermedius artery; TN, troponin.

Objective: The aim of this paper was to report the 2-year follow-up in type I patients treated with Nusinersen and to assess whether possible changes in motor function are related to the subtype, age, or SMN2 copy number. Methods: Sixty-eight patients, with ages ranging from 0.20 to 15.92 years (mean: 3.96; standard deviation: +3.90) were enrolled in the study. All patients were assessed using the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) and the developmental section of the Hammersmith Infant Neurological Examination (HINE-2) at the time they started treatment and 12 and 24 months after that. Results: For both CHOP and HINE-2 repeated measures analysis of variance showed a significant difference (P < 0.001) between baseline and 12 months, 12 months and 24 months, and baseline and 24-month scores for the whole group. When age subgroups (<210 days, <2 years, 2–4 years, 5–11 years, 12–18 years) were considered, on the CHOP INTEND the difference was significant between baseline and 24 months in all age subgroups. On the HINE-2, the difference between baseline and 24 months was significant in all the subgroups before the age of 4 years. Age was predictive of changes on both scales (P < 0.05), whereas SMN2 copy number and decimal classification were not. Interpretation: Our results suggest that some improvement of motor function can be observed even after the first year of treatment. This is more obvious in the infants treated in the first 2 years but some improvement can also be found in older children.

Background: Neurally adjusted ventilatory assist (NAVA) is an innovative mode for assisted ventilation that improves patient-ventilator interaction in children. The aim of this study was to assess the effects of patient-ventilator interaction comparing NAVA with pressure support ventilation (PSV) in patients difficult to wean from mechanical ventilation after moderate pediatric acute respiratory distress syndrome (PARDS). Methods: In this physiological crossover study, 12 patients admitted in the Pediatric Intensive Care Unit (PICU) with moderate PARDS failing up to 3 spontaneous breathing trials in less than 7 days, were enrolled. Patients underwent three study conditions lasting 1 h each: PSV1, NAVA and PSV2. Results: The Asynchrony Index (AI) was significantly reduced during the NAVA trial compared to both the PSV1 and PSV2 trials (p = 0.001). During the NAVA trial, the inspiratory and expiratory trigger delays were significantly shorter compared to those obtained during PSV1 and PSV2 trials (Delaytrinsp p < 0.001, Delaytrexp p = 0.013). These results explain the significantly longer Timesync observed during the NAVA trial (p < 0.001). In terms of gas exchanges, PaO2 value significantly improved in the NAVA trial with respect to the PSV trials (p < 0.02). The PaO2/FiO2 ratio showed a significant improvement during the NAVA trial compared to both the PSV1 and PSV2 trials (p = 0.004). Conclusions: In this specific PICU population, presenting difficulty in weaning after PARDS, NAVA was associated with a reduction of the AI and a significant improvement in oxygenation compared to PSV mode. Trial registration: ClinicalTrial.gov Identifier: NCT04360590 "Retrospectively registered".

Background and Aims: Lipid peroxidation represents a marker of secondary brain injury both in traumatic and in non-traumatic conditions—as in major neurosurgical procedures—eventually leading to brain edema amplification and further brain damage. Malondialdehyde (MDA), a lipid peroxidation marker, and ascorbate, a marker of antioxidant status, can represent early indicators of this process within the cerebrospinal fluid (CSF). We hypothesized that changes in cerebral lipid peroxidation can be measured ex vivo following neurosurgery in children. Methods: Thirty-six children (M:F = 19/17, median age 32.9 months; IQR 17.6–74.6) undergoing neurosurgery for brain tumor removal were admitted to the pediatric intensive care unit (PICU) in the postoperative period with an indwelling intraventricular catheter for intracranial pressure monitoring and CSF drainage. Plasma and CSF samples were obtained for serial measurement of MDA, ascorbate, and cytokines. Results: An early brain-limited increase in lipid peroxidation was measured, with a significant increase from baseline of MDA in CSF (p = 0.007) but not in plasma. In parallel, ascorbate in CSF decreased (p = 0.05). Systemic inflammatory response following brain surgery was evidenced by plasma IL-6/IL-8 increase (p 0.0022 and 0.0106, respectively). No correlation was found between oxidative response and tumor site or histology (according to World Health Organization grading). Similarly, lipid peroxidation was unrelated to the length of surgery (mean 321 ± 73 min), or intraoperative blood loss (mean 20.9 ± 16.8% of preoperative volemia, 44% given hemotransfusions). Median PICU stay was 3.5 days (IQL range 2–5.5 d.), and postoperative ventilation need was 24 h (IQL range 20–61.5 h). The elevation in postoperative MDA in CSF compared with preoperative values correlated significantly with postoperative ventilation need (P = 0.05, r2 0168), while no difference in PICU stay was recorded. Conclusions: Our

To be really effective, conversational agents must integrate well with the characteristics of the humans with whom they interact. This exploratory study focuses on a method for integrating well-assessed methods from the field of social psychology in the design of task-oriented conversational agents in which the dialogue management module is developed through machine learning. In particular, the aim is to achieve agents whose policies could take into account the psychological features of the human interactants to deliver personalized and more effective messages. The paper presents the psychological study performed and outlines the overall theoretical architecture of the software framework proposed. On the psychosocial side, we first assessed the effectiveness of differently framed messages aimed to reducing red meat consumption taking the Theory of Planned Behavior (TPB) as the psychosocial model of reference. Turning to the machine learning field, the resulting Structural Equation Model (SEM) was first translated into a probabilistic predictor using Dynamic Bayesian Network (DBN). In turn, such DBN became the fundamental element of a Partially Observable Markov Decision Processes (POMDP) in a reinforcement learning setting. The possibility to elicit complete interaction policies was then studied by applying Neural Monte Carlo Tree Search (Neural MCTS) methods. The results thus obtained introduce the possibility to develop new multidisciplinary and integrated techniques for the development of automated dialogue managing systems.

Objective: To evaluate the effects of nusinersen on respiratory function of patients with type 1 spinal muscular atrophy. Study design: Observational, longitudinal cohort study. We collected respiratory data from 118 children with type 1 spinal muscular atrophy and differing pulmonary requirements and conducted a semistructured qualitative interview among a subsample of caregivers at baseline, 6 months, and 10 months after the first nusinersen treatment. Patients were stratified according to ventilation modalities and age at study entry. Results: Most patients in our cohort remained stable (84/109 = 77%). More than 80% of the children treated before age 2 years survived, in contrast to the lower survival reported in natural history studies, and did so without tracheostomy or noninvasive ventilation (NIV) ≥16 hours. In those less than 2 years old, only 3 patients shifted from NIV ≤10 hours to NIV >10 hours, and the other 3 reduced the hours of NIV required. Most of the older patients remained stable; this included not only those on tracheostomy or NIV >10 hours but also 75% of those on NIV ≤10 hours. Conclusions: Our results suggest that nusinersen may produce some improvement in the progression of respiratory impairment, both in terms of survival and need for respiratory support ≥16 hours, especially before the age of 2 years.