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.

The lung ultrasound in children with SARS-COV-2 infection: a national multicenter prospective study.

Coronavirus disease-19 (COVID-19) caused hospitalizations, severe disease, and deaths in any age, including in the youngest children. The aim of this multicenter national study is to characterize the clinical and the prognostic role of lung ultrasound (LU) in children with COVID-19. We enrolled children between 1 month and 18 years of age with severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection who underwent a LU within 6 h from the first medical evaluation. A total of 213 children were enrolled, 51.6% were male, median age was 2 years and 5 months (interquartile range (IQR) 4 months -11 years and 4 months). One hundred and forty-eight (69.4%) children were admitted in hospital, 9 (6.1%) in pediatric intensive care unit. We found an inverse correlation between the lung ultrasound score (LUS) and the oxygen saturation at the first clinical evaluation (r = -0.16; p = 0.019). Moreover, LUS was significantly higher in patients requiring oxygen supplementation (8 (IQR 3-19) vs 2 (IQR 0-4); p = 0.001). Among LU pathological findings, irregular pleural lines, subpleural consolidations, and pleural effusions were significantly more frequent in patients needing oxygen supplementation (p = 0.007, p = 0.006, and p = 0.001, respectively).  Conclusion: This multicenter study showed that LU in children with COVID-19 can highlight pleural line irregularities, vertical artifacts, and subpleural consolidation. Notably, children with higher LUS have a higher risk of hospitalization and need for oxygen supplementation, supporting LU as a valid and safe point-of-care first level tool for the clinical evaluation of children with COVID-19. What is Known: • Few children infected with SARS-CoV-2 develop a severe disease and need oxygen therapy. • Lung ultrasound can easily detect low respiratory tract infection during SARS-CoV-2. What is New: • Children with higher lung ultrasound score have a higher risk of need for oxygen supplementation. • Irregular pleural line, sub-pleural consolidations and pleural effusions were significantly more frequent in patients needing oxygen supplementation.

Diagnosis and management of post-COVID (Long COVID) in children: a moving target.

PURPOSE OF REVIEW: This review describes recent findings about post-COVID condition (PCC, or Long COVID) in children, including current knowledge about its epidemiology, clinical presentation, pathogenesis and care. RECENT FINDINGS: There is no internationally agreed definition of PCC, although now most researchers agree that it is a complex clinical symptomatology persisting for at least 3 months after COVID-19, without an alternative diagnosis. There are several uncertainties about paediatric PCC. So far, available literature suggest that 1-3% of recognized children with Severe Acute Respiratory Syndrome COronaVirus 2 (SARS-CoV-2) infection may develop PCC. Its pathogenesis is unknown, although there is increasing evidence about possible abnormalities in the immune responses, cellular metabolism and intestinal microbiota, along with chronic endothelitis. SUMMARY: Management of PCC in children is complex and require a multidisciplinary approach, with the goal of offering the best care possible to support diagnostics, research, mental health and access to research projects.

Lung ultrasound and mediastinal retraction in children.

The authors showed a case of left mediastinal retraction associated with massive left lung collapse suspected after easy visualization of the heart on all scans of the anterolateral left hemithorax. In fact, the figure shows that the apex of the ventricle was visible at the level of the pleural line in the left hemithorax (usually not visible due to pulmonary air artifacts).

Determinants of antibiotic prescriptions in a large cohort of children discharged from a pediatric emergency department.

While there is evidence of high use of wide-spectrum antibiotics in children evaluated in the pediatric emergency departments, determinants of this behavior are still unclear. This study was aimed at defining the demographic, social, clinical, and laboratory factors that affect antibiotic prescriptions in children discharged from the emergency department. We performed a retrospective observational study of children aged younger than 18 years discharged from a pediatric university hospital between Jan. 1, 2015 and Dec. 31, 2020. We determined the proportion and type of antibiotic prescription according to demographic, social, clinical, laboratory, and imaging data, as well as doctor's expertise. Fifty-one thousand six hundred thirty-three children were included, and 13,167 (25.5%) received an antibiotic prescription. Amoxicilline/clavulanate (Am/Cl) was the most prescribed antibiotic (8453, 64.2% of all prescriptions). Factors independently associated with an antibiotic prescription were older age (OR = 1.62 [1.53-1.73] for age 2-5 years, OR = 1.77 [1.64-1.91] for age 6-10 years, OR = 1.36 [1.25-1.49] for age 11-18 years, p < 0.001 for all groups); being evaluated by a physician with > 3 years of pediatric expertise (OR = 1.22 [1.13-1.31], p < 0.001); fever peak higher than 40 °C (OR = 1.37 [1.21-1.54], p < 0.001); abnormal findings on auscultation (OR = 1.95 [1.75-2.17], p < 0.001), CRP values (OR = 1.63 [1.26-2.10] for CRP < 50 mg/L, and OR = 3.78 (2.75-5.21) for CRP ≥ 50 mg/L with respect to CRP not requested; p < 0.01); CXR results whatever positive (OR = 4.47 [3.62-5.52], p < 0.001) or negative (1.82 [1.62-2.04], p < 0.001); being diagnosed with upper respiratory tract infections (OR = 4.27 [4.04-4.51], p < 0.001), lower respiratory tract infections (OR = 5.35 [4.88-5.85]; p < 0.001), and UTI (OR = 9.33 [8.14-10.71], p < 0.001).    Conclusions: Overprescription of antibiotics, including Am/Cl, is relevant in pediatric emergency departments. Factors associated with overprescription are not limited to the clinical characteristics of the treated patients. These findings highlight the need for a new and comprehensive approach to ensure successful antibiotic stewardship initiatives in the emergency departments. What is Known: • Antibiotic resistance is a growing problem in medical practice, including in pediatrics. • Antibiotics are overprescribed in children assessed in the emergency department, but comprehensive and large studies are lacking. What is New: • Factors associated with overprescription are not limited to the clinical characteristics of the patients. • Non-clinical factors such as environmental variables, doctor's expertise, and attitudes to laboratory and radiological examinations affect prescription.

COVID-19 review shows that benefits of vaccinating children and adolescents appear to outweigh risks of post-vaccination myopericarditis.

AIM: Myopericarditis after COVID-19 vaccination were the most serious adverse events reported in children over 5 years of age. We want to summarise these cases, describing their incidence, clinical features, diagnostic pathways, therapeutic strategies and outcome. METHODS: A systematic review of the literature was conducted until 20 March 2022 by bibliographic electronic databases. We included all reports of post-vaccination myopericarditis in children aged between 5 and 18 years. RESULTS: All reported cases had elevated serum Troponin levels, associated with electrocardiogram changes, but often with normal echocardiogram. Cardiac magnetic resonance images always showed typical alterations. The pathogenetic mechanism is still unknown. Myocarditis following post-COVID vaccination is more frequent in boys with an average age of about 15 years. Treatment involves the usage of non-steroidal anti-inflammatory drugs, and the average hospitalisation is about 3 days. The long-term consequences are not yet known, so these patients should be studied in a cardiological follow-up and abstention from physical activity should be recommended. CONCLUSION: The benefits of COVID-19 vaccination in children and adolescents appear to outweigh the risk of developing post-vaccination myopericarditis. We can also speculate a possible approval of vaccination in children under 5 years for the coming winter.

Lung Ultrasound Pattern in Healthy Infants During the First 6 Months of Life.

OBJECTIVES: Lung ultrasound (LUS) has gained a primary role in the diagnosis and management of pleuropulmonary disorders in pediatric practice. However, normal and pathologic patterns are translated from adult studies and have never been specifically studied in children, particularly in infants. This was a prospective observational pilot study aiming to define the normal LUS pattern in healthy infants during the first 6 months of life. METHODS: We recruited healthy neonates at 7 to 10 days of life, and these were followed until the sixth month of life (times: 7-10 days, 1 month, 3 months, and 6 months). We excluded neonates with a gestational age before 33 weeks and neonates with cardiac or lung abnormalities or diseases, immune deficiencies, metabolic or genetic conditions, and acute or chronic respiratory diseases. A LUS evaluation was performed by a single certified pediatrician. The chest wall was examined in 18 areas, addressing A-lines, short and long B-lines, pleural abnormalities, and subpleural consolidations. RESULTS: Thirty-seven neonates were enrolled and followed until the sixth month of life, 27 (73%) of whom were born at term (≥37 weeks) and 10 (27%) of whom were born preterm (33-36 weeks). Most of the patients at 7 to 10 days showed multiple B-lines (long and short) with a progressive normalization toward a normal A pattern at 6 months (P < .00001; 95% confidence interval, 13.75-23.24). No infants showed subpleural consolidations or pleural abnormalities. CONCLUSIONS: This study has implications for the interpretation of LUS during the first 6 months of life. Most healthy infants show a diffuse pattern of vertical artifacts (B-lines), and the LUS pattern tends to be similar to the physiologic pattern (A-lines) after the sixth month of life. The only pathologic LUS findings were pleural irregularities and effusion and subpleural consolidations, which have never been described in healthy infants.

Lung ultrasound findings in pediatric community-acquired pneumonia requiring surgical procedures: a two-center prospective study.

BACKGROUND: Lung ultrasound (US) in the evaluation of suspected pediatric pneumonia is increasingly used and has a recognized role in evaluating pleural effusions, although there are no detailed studies specifically addressing its use in the pediatric population. OBJECTIVES: To define lung US findings of severe pediatric community-acquired pneumonia that required surgical procedures during admission. MATERIALS AND METHODS: Our prospective case-control study compared lung US findings in patients ages 1 month to 17 years admitted with community-acquired pneumonia that required surgical procedures from findings those who did not. Lung US was performed at admission and always before surgical procedures. Medical treatment, laboratory and microbiological findings, chest X-ray, computed tomography scan and surgical procedures are described. RESULTS: One hundred twenty-one children with community-acquired pneumonia were included; of these, 23 underwent surgical intervention. Compared with the control group, children requiring a surgical procedure had a significantly higher rate of large consolidations (52.2%; 95% confidence interval [CI]: 30.6% to 73.2%), larger and complicated pleural effusions (100%; 95% CI: 85.2% to 100%), and both liquid and air bronchograms (73.9%; 95% CI: 51.6% to 89.8%). CONCLUSION: Larger consolidations, larger and more complicated pleural effusions, and liquid and air bronchograms were associated with surgical treatment.

Cardiopulmonary Exercise Testing in Children With Long COVID: A Case-controlled Study.

BACKGROUND: Cardiopulmonary exercise testing (CPET) is a noninvasive and nonexpensive diagnostic tool, that provides a comprehensive evaluation of the pulmonary, cardiovascular, and skeletal muscle systems' integrated reactions to exercise. CPET has been extensively used in adults with Long COVID (LC), while the evidence about its role in children with this condition is scarce. METHODS: Prospective, case-controlled observational study. Children with LC and a control group of healthy children underwent CPET. CPET findings were compared within the 2 groups, and within the LC groups according to main clusters of persisting symptoms. RESULTS: Sixty-one children with LC and 29 healthy controls were included. Overall, 90.2% of LC patients (55 of 61) had a pathologic test vs 10.3% (3/29) of the healthy control. Children with LC presented a statistically significant higher probability of having abnormal values of peak VO2 ( P = 0.001), AT% pred ( P <0.001), VO2/HR % ( P = 0.03), VO2 work slope ( P = 0.002), VE/VCO2 slope ( P = 0.01). The mean VO2 peak was 30.17 (±6.85) in LC and 34.37 (±6.55) in healthy patients ( P = 0.007). CONCLUSIONS: Compared with healthy controls, children with LC have objective impaired functional capacity (expressed by a low VO2 peak), signs of deconditioning and cardiogenic inefficiency when assessed with CPET. As such, CPET should be routinely used in clinical practice to objectify and phenotype the functional limitations of children with LC, and to follow-up them.

Circulating Activated Platelets in Children With Long Covid: A Case-Controlled Preliminary Observation.

We investigated if children with Long Covid (n=14) have activated platelets compared with healthy controls (n=14). Platelet activation and secretion markers were investigated by flow cytometry using MoAbs directed against P-selectin, CD63, and PAC-1 in quiescent platelets and in platelets stimulated with 10-µM adenosine diphosphate and 25-µM protease activated receptor 1-activating peptide. Circulating platelets of patients with Long Covid had significantly increased expression of the activation marker cytometry using MoAbs directed against P-selectin (P = 0.019).

Persisting Gastrointestinal Symptoms in Children with SARS-CoV-2: Temporal Evolution over 18 Months and Possible Role of Lactoferrin.

BACKGROUND AND AIM: Persisting gastrointestinal symptoms are reported to be relatively common in children with long COVID; however, their detailed characterization and long-term outcomes have not yet been described. METHODS: We performed a retrospective study aiming to investigate the temporal evolution of gastrointestinal symptoms in children with SARS-CoV-2, from acute infection to 18-months follow-up. To further investigate possible therapeutic strategies, we evaluated the role of lactoferrin in improving gastrointestinal symptoms in these children, compared with those not treated. RESULTS: A total of 1224 patients (47.7% females) were included. Of these participants, 246 (19.8%) were vaccinated and 143 (11.5%) presented with comorbidities. A total of 175 patients (14.1%) presented gastrointestinal symptoms during acute infection, 54 (4.4%) at three months, 23 (1.9%) at six months, 6 (3.3%) at twelve months, and 2 (2.3%) at eighteen months follow-up. At six months follow-up, children who were treated with 3 months oral lactoferrin had less persisting symptoms compared to those who did not receive lactoferrin, although this difference was not statistically significant (three patients (25%) in the lactoferrin group vs. fourteen patients (33.3%) not treated, p = 0.73), probably due to the low number of patients with persisting GI symptoms. CONCLUSIONS: GI symptoms are relatively common during acute SARS-CoV-2 infection in children, and a non-negligible proportion of these children reported persisting symptoms for up to 12-18 months after the acute infection. In addition, we found a trend even if statistically nonsignificant toward faster improvement of persisting gastrointestinal symptoms in children with long COVID treated with lactoferrin. Despite the limitations relating to the present study's design, given the significant burden of gastrointestinal symptoms in children with long COVID, our findings provide the basis to perform a prospective, placebo-controlled study.

Changes in clinical, demographic, and outcome patterns of children hospitalized with non-SARS-CoV-2 viral low respiratory tract infections before and during the COVID pandemic in Rome, Italy.

INTRODUCTION: We performed this study aiming to evaluate changes in epidemiology, clinical presentation and outcomes of children hospitalized for viral lower respiratory tract infections (LRTI). METHODS: We performed a retrospective study of children younger than 18 years of age hospitalized for LRTIs with a positive respiratory viral testing from 2018 to 2022. We compared 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. RESULTS: A total of 523 were included in the analysis. In the pandemic period, the detection of influenza was 95% less likely to occur (odds ratio [OR]: 0.05; 95% confidence interval [95% CI]: 0.02-0.12; p < .001), likewise the detection of adenovirus was 77% less likely to occur (OR: 0.23; 95% CI: 0.10-0.51; p < .001). In the pandemic period, the number of codetections increased from 15.52% in 2018 to 57.25% in 2022, resulting in a significantly increasing trend (p < .001). The odds of transfer to PICU was more than five times greater during the pandemic period (OR: 5.31; 95% CI: 1.78-15.86; p = .003). CONCLUSIONS: We found that the pattern of LRTI in children during COVID-19 pandemic significantly changed in terms of etiologies and increased severity.

Utility of Rapid Nasopharyngeal Swab for Respiratory Pathogens in the Diagnosis of Viral Infections in Children Hospitalized with Fever: A Prospective Validation Study to Improve Antibiotic Use.

Introduction: Fever is among the most common reason for medical assessment and antibiotic prescription in practice. The aim of this study was to evaluate positive and negative predictive values of rapid nasopharyngeal swabs for respiratory pathogens to discriminate viral from bacterial infections. Methods: We prospectively tested children with signs and/or symptoms of infections (e.g., fever, cough, wheezing, suspected urinary tract infection) admitted to a paediatric department. Following discharge, clinical phenotypes were assigned defining a cohort of children having probable/certain viral infection, probable/certain bacterial infection, other inflammatory conditions or healthy controls. Results: In this study, 190 children were enrolled (50.5% females, median age 30.5 (8-86) months). In total, 102 patients (53.7%) were affected by respiratory viral infections, 16 (8.4%) by bacterial infections, 29 (15.3%) were healthy controls and 43 (22.6%) were affected by another pathological condition manifested with fever. In total, 84.3% of patients classified as viral infection tested positive for viruses, compared with 18.8% of patients with bacterial infection (p < 0.001), 18.6% of patients with other condition (p < 0.001) and 17.2% of control patients (p < 0.001). The positive predictive value of NPSs in the diagnosis of viral infection was 88.6% and the negative predictive value was 75.0%. Conclusion: Our findings suggest that rapid NPS tests for respiratory viruses are a useful tool to confirm viral infections in children with fever and improve antibiotic use.

Chest ultrasound findings in hepatopulmonary fusion (HPF).

Hepatopulmonary fusion (HPF) is an extremely rare condition characterized by a fusion between the herniated liver and lung right parenchyma. Knowledge about this condition comes from the few cases reported in the literature (less than 40 cases). While diagnostic evaluation as X-Ray, Computed Tomography (CT), Magnetic Resonance Imaging (MRI), and Single Photon Emission Computed Tomography (SPECT) were described, poor ultrasound findings are available. In this paper, the authors provide the detailed chest ultrasound findings of this rare condition.