Lung ultrasound-guided best positive end-expiratory pressure in neonatal anesthesia: a proposed randomized, controlled study.

BACKGROUND: Atelectasis is a common complication in neonatal anesthesia. Lung ultrasound (LUS) can be used intraoperatively to evaluate and recognize atelectatic lung areas. Hypotheses for the study are: (1) The use of LUS to guide choice of best positive end-expiratory pressure (PEEP) can lead to reduction of FiO2 to achieve same saturations of oxygen (SpO2). (2) In a less de-recruited lung, there will be less postoperative pulmonary complications. (3) Static respiratory system compliance could be different. (4) Hemodynamic parameters and amount of fluids infused or need for vasopressors intraoperatively could be different. METHODS: We propose a randomized controlled trial that compares standard PEEP settings with LUS-guided PEEP choice in patients under 2 months of age undergoing general anesthesia. RESULTS: The primary aim is to determine whether LUS-guided PEEP choice in neonatal anesthesia, compared to standard PEEP choice, can lead to reduction of FiO2 applied to the ventilatory setting in order to maintain same SpO2s. Secondary aims are to determine whether patients treated with LUS-guided PEEP will develop less postoperative pulmonary complications, will have a significant difference in hemodynamic parameters and amount of fluids or vasopressors infused, and in static respiratory system compliance. CONCLUSIONS: We expect a significant reduction of FiO2 in LUS-guided ventilation. IMPACT: Lung atelectasis is extremely common in neonatal anesthesia, because of the physiology of the neonatal lung and chest wall and leads to hypoxemia, being a lung area with a perfusion/ventilation mismatch. Raising inspired fraction of oxygen can overcome temporarily hypoxemia but oxygen is a toxic compound for newborns. Lung ultrasound (LUS) can detect atelectasis at bedside and be used to optimize ventilator settings including choice of positive end-expiratory pressure (PEEP). This randomized controlled trial (RCT) aims at demonstrating that LUS-guided choice of best PEEP during neonatal anesthesia can lead to reduction of inspired fractions of oxygen to keep same peripheral saturations SpO2.

Management and outcomes of bronchiolitis in Italy and Latin America: a multi-center, prospective, observational study.

We aimed to describe differences in the epidemiology, management, and outcomes existing between centers located in countries which differ by geographical location and economic status during to post-pandemic bronchiolitis seasons.  This was a prospective observational cohort study performed in two academic centers in Latin America (LA) and three in Italy. All consecutive children with a clinical diagnosis of bronchiolitis were included, following the same data collection form.  Nine hundred forty-three patients have been enrolled: 275 from the two Latin American Centers (San Jose, 215; Buenos Aires, 60), and 668 from Italy (Rome, 178; Milano, 163; Bologna, 251; Catania, 76). Children in LA had more frequently comorbidities, and only rarely received palivizumab. A higher number of patients in LA had been hospitalized in a ward (64% versus 23.9%, p < 0.001) or in a PICU (16% versus 6.2%, p < 0.001), and children in LA required overall more often respiratory support, from low flow oxygen to invasive mechanical ventilation, except for CPAP which was more used in Italy. There was no significant difference in prescription rates for antibiotics, but a significantly higher number of patients treated with systemic steroids in Italy. CONCLUSIONS: We found significant differences in the care for children with bronchiolitis in Italy and LA. Reasons behind such differences are unclear and would require further investigations to optimize and homogenize practice all over the world. WHAT IS KNOWN: • Bronchiolitis is among the commest cause of morbidity and mortality in infants all over the world. WHAT IS NEW: • There are significant differences on how clinicians care for bronchiolitis in different centers and continents. Differences in care can be principally due to different local practices than differences in patients severity/presentations. • Understanding these differences should be a priority to optime and standardize bronchiolitis care globally.

Determinants of antibiotic prescription in children with adenovirus respiratory tract infections.

We performed this study to evaluate factors associated with antibiotic prescriptions in children with adenovirus infection, since no studies have attempted to address this aspect in the pediatric population. Retrospective study of children younger than 18 years of age tested positive for adenovirus on a syndromic nasopharyngeal test from 2018 to 2023. We compared the need of pediatric intensive care unit (PICU), invasive ventilation, and other respiratory support, viral etiologies, clinical presentations, imaging, and laboratory results in the precovid (2018-2019) and covid (2020-2022) period. The use of antibiotics was studied with multivariable logistic regression including demographic as well as clinical data as covariates. Two hundred fifty-eight patients were enrolled. One hundred fifty-eight patients received an antibiotic (mean duration 6.2 (±2.7) days (median 4; IQR: 4-7)). Presence of seizures and C-reactive protein values as predictors for antibiotic prescription (OR for seizures: 12.17; 95% CI: 1.42-103.91; p = 0.022; OR for CrP: 1.03; 95% CI: 1.01-1.04; p = 0.001). Seventy-four patients received intravenous antibiotics (74/156, 47.4%). Risk factors for intravenous antibiotic were the presence of decay (OR: 3.74; 95% CI: 1.25-11.71; p = 0.018), CrP values (OR: 1.02; 95% CI: 1.00-1.03; p = 0.001), and presence of seizures (OR: 16.34; 95% CI: 2.65-100.83; p = 0.003). Duration of intravenous antibiotics correlated with the presence of seizures (Coeff: 1.6; 95% CI: 0.41-2.89; p = 0.009) even when adjusted for CrP values.    Conclusion: The clinical presentation of adenovirus infection in children is non-specific, leading to frequent antibiotic prescription despite bacterial co-infections was rare. Higher CrP values and presenting with seizures are significantly associated with a higher risk of receiving antibiotics. Rapid microbiological tests and newer biomarkers can help clinicians to improve antibiotic prescription in this cohort of children. What is Known: • Adenovirus infection is a common cause of fever and respiratory tract infections in children. • Children with adenovirus infections frequently receive antibiotics, but determinants of this practice are poorly established. What is New: • Higher C-reactive protein values and presenting with seizures are significantly associated with antibiotic prescription. • Since the beginning of COVID-19 and implementation of rapid diagnostics, less children with adenovirus infection received antibiotics.

FDXR-associated disease: a challenging differential diagnosis with inflammatory peripheral neuropathy.

BACKGROUND AND AIMS: Mutations in FDXR gene, involved in mitochondrial pathway, cause a rare recessive neurological disorder with variable severity of phenotypes. The most common presentation includes optic and/or auditory neuropathy, variably associated to developmental delay or regression, global hypotonia, pyramidal, cerebellar signs, and seizures. The review of clinical findings in previously described cases from literature reveals also a significant incidence of sensorimotor peripheral polyneuropathy (22.72%) and ataxia (43.18%). To date, 44 patients with FDXR mutations have been reported. We describe here on two new patients, siblings, who presented with a quite different phenotype compared to previously described patients. METHODS: Clinical, neurophysiological, and genetic features of two siblings and a systematic literature review focused on the clinical spectrum of the disease are described. RESULTS: Both patients presented with an acute-sub-acute onset of peripheral neuropathy and only in later stages of the disease developed the typical features of FDXR-associated disease. INTERPRETATION: The peculiar clinical presentation at onset and the evolution of the disease in our patients and in some cases revised from the literature shed lights on a new possible phenotype of FDXR-associated disease: a peripheral neuropathy which can mimic an acute inflammatory disease.

Modified fluid gelatin 4% for perioperative volume replacement in pediatric patients (GPS): Results of a European prospective noninterventional multicenter study.

INTRODUCTION: Modified fluid gelatin 4% is approved for use in children, but there is still a surprising lack of clinical studies including large numbers of pediatric patients. Therefore, we performed a European prospective noninterventional multicenter study to evaluate the use of a modified fluid gelatin 4% in saline (sal-GEL) or an acetate-containing balanced electrolyte solution (bal-GEL) in children undergoing major pediatric surgery. AIMS: The primary aim was to assess the indications and dosing of modified fluid gelatin, and the secondary aim was to assess the safety and efficacy, focusing, in particular, on routinely collected clinical parameters. METHODS: Children aged up to 12 years with ASA risk scores of I-III receiving sal-GEL or bal-GEL were followed perioperatively. Demographic data, surgical procedures performed, anesthesia, hemodynamic and laboratory data, adverse events, and adverse drug reactions were documented using a standardized case report form. RESULTS: 601 children that were investigated at 13 European pediatric centers from May 2015 to March 2020 (sal-GEL 20.1%, bal-GEL 79.9%; mean age 29.1 ± 38.6 (range 0-144) months; body weight 12.1 ± 10.5 (1.4-70) kg) were included in the analysis. The most frequent indications for GEL infusion were hemodynamic instability without bleeding (76.0%), crystalloids alone not being sufficient for hemodynamic stabilization (55.7%), replacement of preoperative deficit (26.0%), and significant bleeding (13.0%). Mean infused GEL volume was 13.0 ± 5.3 (2.4-37.5) ml kg-1 . The total dose was affected by age, with higher doses in younger patients. After gelatin infusion, mean arterial pressure increased (mean change 8.5 ± 7.3 [95% CI: 8 to 9.1] mmHg), and the hemoglobin concentrations decreased significantly (mean change -1.1 ± 1.8 [95% CI: -1.2 to -0.9] g·dL-1 ). Acid-base parameters were more stable with bal-GEL. No serious adverse drug reactions directly related to gelatin (i.e., anaphylactoid reaction, clotting disorders, and renal failure) were observed. CONCLUSION: Moderate doses up to 20 ml kg-1 of modified fluid gelatin were infused most frequently to improve hemodynamic stability in children undergoing major pediatric surgery. The acid-base balance was more stable when gelatin in a balanced electrolyte solution was used instead of saline. No serious adverse drug reactions associated with gelatin were observed.

Organizational aspects of pediatric anesthesia and surgery between two waves of Covid-19.

BACKGROUND: The initial wave of the Covid-19 pandemic has hit Italy, and Lombardy in particular, with violence, forcing to reshape all hospitals' activities; this happened even in pediatric hospitals, although the young population seemed initially spared from the disease. "Vittore Buzzi" Children's Hospital, which is a pediatric/maternal hospital located in Milan (Lombardy Region), had to stop elective procedures-with the exception of urgent/emergent ones-between February and May 2020 to leave space and resources to adults' care. We describe the challenges of reshaping the hospital's identity and structure, and restarting pediatric surgery and anesthesia, from May on, in the most hit area of the world, with the purpose to avoid and contain infections. Both patients and caregivers admitted to hospital have been tested for Sars-CoV-2 in every case. METHODS: Observational cohort study via review of clinical charts of patients undergoing surgery between 16th May and 30th September 2020, together with SARS-CoV -2 RT-PCR testing outcomes, and comparison to same period surgeries in 2019. RESULTS: An increase of approximately 70% in pediatric surgeries (OR 1.68 [1.33-2.13], P < .001) and a higher increase in the number of surgeries were reported (OR 1.75 (1.43-2.15), P < .001). Considering only urgent procedures, a significant difference in the distribution of the type of surgery was observed (Chi-squared P-value < .001). Sars-CoV-2-positive patients have been 0.8% of total number; 14% of these was discovered through caregiver's positivity. CONCLUSION: We describe our pathway for safe pediatric surgery and anesthesia and the importance of testing both patient and caregiver.

Protecting children from iatrogenic harm during COVID19 pandemic.

Critical care management of patients with COVID-19 has been influenced by a mixture of public, media and societal pressure, as well as clinical and anecdotal observations from many prominent researchers and key opinion leaders. These factors may have affected the principles of evidence-based medicine and encouraged the widespread use of non-tested pharmacological and aggressive respiratory support therapies, even in intensive care units (ICUs). The COVID-19 pandemic has predominantly affected adult populations, while children appear to be relatively spared of severe disease. Notwithstanding, paediatric intensive care (PICU) clinicians may already have been influenced by changes in practices of adult ICUs, and these changes may pose unintended consequences to the vulnerable population in the PICU. In this article, we analyse several potential iatrogenic causes of the detrimental effects of the current pandemic to children and highlight the risks underlying a sudden change of clinical practice.

Minimal Access in Pediatric Surgery: An Overview on Progress towards Dedicated Instrument Developments and Anesthesiologic Advances to Enhance Safe Completion of Procedures.

Surgical techniques are evolving in Pediatric Surgery, especially in the area of minimal access surgery (MAS) where indications for applications are expanding. Miniaturization of instruments, using natural orifices, single incisions, or remotely controlled robot-assisted procedures, promises to increase the benefits of MAS procedures in pediatrics. Many pediatric pathologies are rare, and specialized surgical and anesthesiologic instruments are necessary to manage them, defined as "orphan devices", for which development and dissemination on the market are slowed down or sometimes hindered by regulatory standards and limiting financial conflicts of interest. In pediatric surgery, it is of utmost importance to work in a multidisciplinary way to offer a surgical path that is safe and supported by technological advances. For this reason, optimizing pediatric anesthesia is also a crucial factor where technological advances have made monitoring more precise, thereby enhancing safety in the operative room. The development of customized instruments and technologies should be supported by pediatric research and should be adapted to the individualities of the small patient. This overview outlines the importance of dedicated instruments developed for the safe completion of MAS procedures in pediatrics.

Lung ultrasound assessment of atelectasis following different anesthesia induction techniques in pediatric patients: a propensity score-matched, observational study.

INTRODUCTION: Atelectasis is a well-documented complication in pediatric patients undergoing general anesthesia. Its incidence varies significantly based on surgical procedures and anesthesia techniques. Inhalation induction, commonly used to avoid the discomfort of venipuncture, is suspected to cause higher rates of respiratory complications, including atelectasis, compared to intravenous induction. This study aimed to evaluate the impact of inhalation versus intravenous anesthesia induction on atelectasis formation in pediatric patients, as assessed by lung ultrasound (LUS). METHODS: This propensity score-matched observational study was conducted at a tertiary pediatric hospital in Milan, Italy. Inclusion criteria were children ≤ 18 years undergoing elective surgery with general anesthesia. Patients were divided into inhalation and intravenous induction groups. LUS was performed before and after anesthesia induction to assess lung aeration. The primary endpoint was the global LUS score post-induction, with secondary endpoints including the incidence and distribution of atelectasis. RESULTS: Of the 326 patients included, 65% underwent inhalation induction and 35% intravenous induction. The global LUS score was significantly higher in the inhalation group (12.0 vs. 4.0, p < 0.001). After propensity score matching (for age, presence of upper respiratory tract infection, duration of induction, and PEEP levels at induction), average treatment effect (ATE) of mask induction was 5.89 (95% CI, 3.21-8.58; p < 0.001) point on LUS global score and a coefficient of 0.35 (OR 1.41) for atelectasis. DISCUSSION: Inhalation induction is associated with a higher incidence of atelectasis in pediatric patients also when we adjusted for clinically relevant covariates. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06069414.

Characteristics and predictors of Long Covid in children: a 3-year prospective cohort study.

Background: Children can develop Long Covid, however long term outcomes and their predictors are poorly described in these patients. The primary aim is to describe characteristics and predictors of Long Covid in children assessed in-clinics up to 36 months post-SARS-CoV-2 infection, as well as investigate the role of vaccines in preventing Long Covid, risk of reinfections and development of autoimmune diseases. Methods: Children aged 0-18 years old with confirmed SARS-CoV-2 infection were invited for a prospective follow-up assessment at a peadiatric post-covid clinic in Rome, Italy, at serial intervals (3-, 6-, 12-, 18-, 24- and 36-months post-infection onset, between 01/02/2020 and 28/02/2024). Long Covid was defined as persistence of otherwise unexplained symptoms for at least three months after initial infection. Findings: 1319 patients were initially included, 1296 reached the 3 months follow-up or more. Of the patients who underwent multiple follow-ups, 23.2% (301), 169 (13.2%), 89 (7.9%), 67 (6.1%), 47 (7.1%) were diagnosed with Long Covid at 3-6-12-18-24 months, respectively For the primary outcome of Long Covid at three months, age >12 years (P < 0.001, OR 11.33, 95% CI 4.2; 15.15), comorbidities (P = 0.008, OR 1.83, 95% CI 1.06; 2.44), being infected with original variants (P < 0.001, OR 4.77, 95% CI 2.46; 14.47), female sex (P < 0.001, OR 1.62, 95% CI 1.02; 1.89) were statistically significant risk factors. Age >12 years (P = 0.002, OR 9.37, 95% CI 1.58; 8.64), and infection with original (P = 0.012, OR 3.52, 95% CI 1.32; 8.64) and alfa (P < 0.001, OR 4.09, 95% CI 2.01; 8.3) SARS-CoV-2 variants remained statistically significant risk factors for Long Covid duration for at least 18 months. Vaccination was associated with a lower risk of long covid at 3, 6 and 12 months for older children and a lower risk of reinfections. Being infected with the original SARS-CoV-2 variant was associated with a higher risk of new-onset autoimmune diseases ((P = 0.035, 95% CI 1.12; 2.4). One patient was diagnosed with Long Covid after a re-infection. Interpretation: This is the longest follow-up study of children with SARS-CoV-2 infection, showing a significant and long-lasting burden of Long Covid in the pediatric population. Our findings highlight the urgent need of investing in pediatric Long Covid in order to find effective diagnostic and therapeutic approaches, as well can inform preventive strategies in case of future pandemics. Funding: This study has been funde by Pfizer non-competitive grant, granted to DB (#65925795).

Virtual Reality Head-Mounted Display (HMD) and Preoperative Patient-Specific Simulation: Impact on Decision-Making in Pediatric Urology: Preliminary Data.

AIM OF THE STUDY: To assess how virtual reality (VR) patient-specific simulations can support decision-making processes and improve care in pediatric urology, ultimately improving patient outcomes. PATIENTS AND METHODS: Children diagnosed with urological conditions necessitating complex procedures were retrospectively reviewed and enrolled in the study. Patient-specific VR simulations were developed with medical imaging specialists and VR technology experts. Routine CT images were utilized to create a VR environment using advanced software platforms. The accuracy and fidelity of the VR simulations was validated through a multi-step process. This involved comparing the virtual anatomical models to the original medical imaging data and conducting feedback sessions with pediatric urology experts to assess VR simulations' realism and clinical relevance. RESULTS: A total of six pediatric patients were reviewed. The median age of the participants was 5.5 years (IQR: 3.5-8.5 years), with an equal distribution of males and females across both groups. A minimally invasive laparoscopic approach was performed for adrenal lesions (n = 3), Wilms' tumor (n = 1), bilateral nephroblastomatosis (n = 1), and abdominal trauma in complex vascular and renal malformation (ptotic and hypoplastic kidney) (n = 1). Key benefits included enhanced visualization of the segmental arteries and the deep vascularization of the kidney and adrenal glands in all cases. The high depth perception and precision in the orientation of the arteries and veins to the parenchyma changed the intraoperative decision-making process in five patients. Preoperative VR patient-specific simulation did not offer accuracy in studying the pelvic and calyceal anatomy. CONCLUSIONS: VR patient-specific simulations represent an empowering tool in pediatric urology. By leveraging the immersive capabilities of VR technology, preoperative planning and intraoperative navigation can greatly impact surgical decision-making. As we continue to advance in medical simulation, VR holds promise in educational programs to include even surgical treatment of more complex urogenital malformations.

Lung ultrasound among Expert operator'S: ScOring and iNter-rater reliability analysis (LESSON study) a secondary COWS study analysis from ITALUS group.

BACKGROUND: Lung ultrasonography (LUS) is a non-invasive imaging method used to diagnose and monitor conditions such as pulmonary edema, pneumonia, and pneumothorax. It is precious where other imaging techniques like CT scan or chest X-rays are of limited access, especially in low- and middle-income countries with reduced resources. Furthermore, LUS reduces radiation exposure and its related blood cancer adverse events, which is particularly relevant in children and young subjects. The score obtained with LUS allows semi-quantification of regional loss of aeration, and it can provide a valuable and reliable assessment of the severity of most respiratory diseases. However, inter-observer reliability of the score has never been systematically assessed. This study aims to assess experienced LUS operators' agreement on a sample of video clips showing predefined findings. METHODS: Twenty-five anonymized video clips comprehensively depicting the different values of LUS score were shown to renowned LUS experts blinded to patients' clinical data and the study's aims using an online form. Clips were acquired from five different ultrasound machines. Fleiss-Cohen weighted kappa was used to evaluate experts' agreement. RESULTS: Over a period of 3 months, 20 experienced operators completed the assessment. Most worked in the ICU (10), ED (6), HDU (2), cardiology ward (1), or obstetric/gynecology department (1). The proportional LUS score mean was 15.3 (SD 1.6). Inter-rater agreement varied: 6 clips had full agreement, 3 had 19 out of 20 raters agreeing, and 3 had 18 agreeing, while the remaining 13 had 17 or fewer people agreeing on the assigned score. Scores 0 and score 3 were more reproducible than scores 1 and 2. Fleiss' Kappa for overall answers was 0.87 (95% CI 0.815-0.931, p < 0.001). CONCLUSIONS: The inter-rater agreement between experienced LUS operators is very high, although not perfect. The strong agreement and the small variance enable us to say that a 20% tolerance around a measured value of a LUS score is a reliable estimate of the patient's true LUS score, resulting in reduced variability in score interpretation and greater confidence in its clinical use.

Cytokine Profile in Children Following SARS-CoV-2 Infection: Preliminary Findings.

We provide preliminary evidence that, also in children, Long coronavirus disease (COVID) may be characterized by a proinflammatory signature. Ten Long COVID patients, 7 convalescent subjects after COVID infection and 4 healthy controls were enrolled. When adjusted for sex, children with long COVID had statistically significant differences in the levels of Flt3L, CD5, uPA, CCL23, CD40 and TGFα. When adjusted for age, CCL23 levels remained statistically significant.

COVID-19 and Children: Reflections after Three Years.

Three years after the beginning of the COVID-19 pandemic, enough experience has been gained to derive reflections on the impact of SARS-CoV-2 in children [...].