Diagnostic Delay of Celiac Disease in Childhood.

Importance: The extent and factors associated with risk of diagnostic delay in pediatric celiac disease (CD) are poorly understood. Objectives: To investigate the diagnostic delay of CD in childhood, and to assess factors associated with this delay. Design, Setting, and Participants: Multicenter, retrospective, cross-sectional study (2010-2019) of pediatric (aged 0-18 years) patients with CD from 13 pediatric tertiary referral centers in Italy. Data were analyzed from January to June 2023. Main Outcomes and Measures: The overall diagnostic delay (ie, the time lapse occurring from the first symptoms or clinical data indicative of CD and the definitive diagnosis), further split into preconsultation and postconsultation diagnostic delay, were described. Univariable and multivariable linear regression models for factors associated with diagnostic delay were fitted. Factors associated with extreme diagnostic delay (ie, 1.5 × 75th percentile) and misdiagnosis were assessed. Results: A total of 3171 patients with CD were included. The mean (SD) age was 6.2 (3.9) years; 2010 patients (63.4%) were female; and 10 patients (0.3%) were Asian, 41 (1.3%) were Northern African, and 3115 (98.3%) were White. The median (IQR) overall diagnostic delay was 5 (2-11) months, and preconsultation and postconsultation diagnostic delay were 2 (0-6) months and 1 (0-3) month, respectively. The median (IQR) extreme overall diagnostic delay (586 cases [18.5%]) was 11 (5-131) months, and the preconsultation and postconsultation delays were 6 (2-120) and 3 (1-131) months, respectively. Patients who had a first diagnosis when aged less than 3 years (650 patients [20.5%]) showed a shorter diagnostic delay, both overall (median [IQR], 4 [1-7] months for patients aged less than 3 years vs 5 [2-12] months for others) and postconsultation (median [IQR], 1 [0-2] month for patients aged less than 3 years vs 2 [0-4] months for others). A shorter delay was registered in male patients, both overall (median [IQR], 4 [1-10] months for male patients vs 5 [2-12] months for female patients) and preconsultation (median [IQR], 1 [0-6] month for male patients vs 2 [0-6] months for female patients). Family history of CD was associated with lower preconsultation delay (odds ratio [OR], 0.59; 95% CI, 0.47-0.74) and lower overall extreme diagnostic delay (OR, 0.75; 95% CI, 0.56-0.99). Neurological symptoms (78 patients [21.5%]; OR, 1.35; 95% CI, 1.03-1.78), gastroesophageal reflux (9 patients [28.1%]; OR, 1.87; 95% CI, 1.02-3.42), and failure to thrive (215 patients [22.6%]; OR, 1.62; 95% CI, 1.31-2.00) showed a more frequent extreme diagnostic delay. A previous misdiagnosis (124 patients [4.0%]) was more frequently associated with gastroesophageal reflux disease, diarrhea, bloating, abdominal pain, constipation, fatigue, osteopenia, and villous atrophy (Marsh 3 classification). Conclusions and Relevance: In this cross-sectional study of pediatric CD, the diagnostic delay was rather short. Some factors associated with risk for longer diagnostic delay and misdiagnosis emerged, and these should be addressed in future studies.

Towards genomic-Newborn Screening: Technical feasibility of Exome Sequencing starting from dried blood spots.

Each year thousands of babies are born with rare genetic disorders not identified by current NBS panels, due to programs which are not yet optimal. Next-generation sequencing technologies have the potential to overcome many NBS drawbacks and provide large amounts of molecular data, broadening the number of diseases investigated. Here, we design and set up an NGS-based approach to evaluate the feasibility of NGS from dried blood spot starting from 34 DBSs. After assessing gDNA yield and integrity, libraries were performed using three target enrichment approaches, sequenced on NS500 platform, and analyzed on commercial platform. Specifically, we focus on virtual gene panels related to highly actionable neonatal/pediatric disorders. WES show that amount and quality of DBS-extracted gDNA are suitable for high-throughput sequencing. We obtain 500-1500 ng for each specimen, 1.7-1.8 260/280 wavelength, and DIN of 7 resulting DNA integrity, on par with traditional venous blood collection. A high read depth with 94.3% coverage uniformity is achieved for all samples. Data results on mean coverage are comparable among the different workflows tested and demonstrate that DBS from newborn collected at birth is a suitable material for the developing of gNBS programs.

Pediatric Lyme Disease in Northern Italy: An 18-Year Single-Center Case Series.

Tracing the profile of pediatric Lyme borreliosis (LB) in Europe is difficult due to the interregional variation in its incidence and lack in notifications. Moreover, the identification of LB can be challenging. This study is an 18-year case series of 130 children and adolescents aged under 18 years referred to the Pediatric Infectious Diseases Unit at L. Sacco Hospital, Milan, with suspicion of LB, between January 2005 and July 2023. The routine serological workup consisted of a two-step process: an initial screening test followed by Western blot (WB). Forty-four (34%) patients were diagnosed with LB. The median age was six years, and 45% were females. Of the children with erythema migrans (EM), 33 (57%) were confirmed as having true EM, and, of these, 4 (12%) were atypical. Ten (23%) patients had early disseminated/late diseases, including facial nerve palsy (n = 3), early neuroborreliosis (n = 1), arthritis (n = 3), relapsing fever (n = 2), and borrelial lymphocytoma (n = 1). No asymptomatic infections were documented. Over seventy percent of confirmed LB cases (n = 31/44) recalled a history of tick bites; in this latter group, 19 (61%) were from the area of the Po River valley in Lombardy. Almost half of the children evaluated for LB complained of non-specific symptoms (fatigue, musculoskeletal pain, skin lesions/rash, and persistent headache), but these symptoms were observed in only two patients with confirmed LB. Most LB cases in our study were associated with EM; two-tier testing specificity was high, but we found frequent non-adherence to international recommendations with regard to the timing of serology, application of the two-step algorithm, and antibiotic over-prescription. Most children were initially assessed for a tick bite or a skin lesion suggestive of EM by a family pediatrician, highlighting the importance of improving awareness and knowledge around LB management at the primary healthcare level. Finally, the strengthening of LB surveillance at the national and European levels is necessary.

Corrigendum: Newborn screening for X-linked adrenoleukodystrophy in Italy: diagnostic algorithm and disease monitoring.

[This corrects the article DOI: 10.3389/fneur.2022.1072256.].

Lung Function Evaluated By Structured Light Plethysmography in Children After Lung Surgery: A Preliminary Analysis.

Background: Structured light plethysmography (SLP) is a novel light-based method that captures chest wall movements to evaluate tidal breathing. Methods: Thirty-two children who underwent lung surgery were enrolled. Their clinical history was collected along with spirometry and SLP. Results: Median age of surgery was 9 months (interquartile range 4-30). Most frequent diagnosis was congenital pulmonary airway malformation (14/32), then pulmonary sequestration (9/32), tumor (5/32), and bronchogenic cyst (4/32). The most frequent surgical approach was lobectomy (59%), segmentectomy (38%), and complete resection (3%). More than 80% had surgery when younger than 3 years of age. Eight patients had short-term complications (pleural effusion was the most frequent), while long-term effects were reported in 15 patients (19% recurrent cough, 13% thoracic deformities, 13% airway infections, 9% wheezing, 6% reduced exercise tolerance, and 3% columnar deformities). Spirometry was normal in 9/22 patients. Nine patients had a restrictive pattern, while 4 showed a mild bronco-reactivity. Ten patients did not perform spirometry because of young age. SLP revealed the presence of obstructive pattern in 10% of patients (IE50 > 1.88) and showed a significant difference between the two hemithorax in 29% of patients. Discussion: SLP may be a new method to evaluate lung function, without collaboration and radiation exposure, in children who underwent lung resection, also in preschool age.

Recurrent Respiratory Infections in Children with Down Syndrome: A Review.

Down Syndrome (DS) is the most common chromosomal abnormality compatible with life. The life of patients suffering from DS can be strongly impacted by Recurrent Respiratory tract Infections (RRIs), leading to an increased rate of hospitalisation, a higher need for intensive care and fatality. With a literature review, we summarise here the main etiological factors for RRI in this category of patients, particularly focusing on airway malformations such as tracheomalacia, tracheal bronchus and bronchomalacia, comorbidities associated with the syndrome, like congenital heart diseases, dysphagia, gastroesophageal reflux, musculoskeletal involvement and obesity, and immunologic impairments, involving both innate and adaptive immunity. For these patients, a multidisciplinary approach is imperative as well as some preventive strategies, in particular vaccinations in accordance with their national schedule for immunization.

Use of complementary and alternative medicine in children affected by oncologic, neurologic and liver diseases: a narrative review.

Complementary and alternative medicine (CAM) consist of a broad group of restorative resources often linked to existing local cultures and established health care systems and are also increasingly used in children with some serious illnesses. In this narrative review, we examine the epidemiology of the use, efficacy, and safety of complementary and alternative medicine in pediatric oncology, neurology, and hepatology. We searched for relevant articles published in Pubmed evaluating CAM use and its efficacy in safety in children affected by oncologic, neurologic and liver diseases. CAM is used to improve the success of conventional therapies, but also to alleviate the pain, discomfort, and suffering resulting from the diseases and their treatment, which are often associated with a significant burden of adverse effects. CAM use must be evaluated in children with neurological, oncological and liver diseases.

Early lung diffusion abnormalities and airways' inflammation in children with type 1 diabetes.

BACKGROUND AND AIMS OF THE STUDY: Type 1 diabetes (T1D) impacts lung function and exercise capacity in adults, but limited information is available in children. We hypothesize that T1D causes alterations in pulmonary function and cardiorespiratory fitness, i.e., exercise capacity, at early stages of the disease, due to the presence of inflammation and vascular damage. Therefore, we aim to investigate pulmonary function before and after exercise in children with T1D as compared to age matched healthy controls. METHOD: Twenty-four children with T1D and twenty healthy controls underwent body plethysmography, diffusion lung capacity for carbon monoxide and fractional exhaled nitric oxide at rest and after cardio-pulmonary exercise test. RESULTS: In children with T1D, baseline total lung capacity and diffusion lung capacity for carbon monoxide were reduced as compared to healthy controls. Children with T1D also showed a reduced exercise capacity associated with poor aerobic fitness. Accordingly, diffusion lung capacity for carbon monoxide tended to increase with exercise in healthy controls, while no change was observed in children with T1D. Fractional exhaled nitric oxide was significantly higher at baseline and tended to increase with exercise in children with T1D, while no changes were observed in healthy controls. CONCLUSIONS: Altered diffusion lung capacity for carbon monoxide, increased fractional exhaled nitric oxide and a poor aerobic fitness to exercise suggests the presence of early pulmonary abnormalities in children with T1D.

Resting energy expenditure in children and adolescents with cerebral palsy: accuracy of available prediction formulas and development of population-specific methods.

Introduction: Energy requirements are difficult to estimate in children with cerebral palsy (CP). Resting energy expenditure (REE), necessary to implement personalized nutritional interventions, is most commonly estimated using prediction formulae since indirect calorimetry, the reference method, is not available in all nutrition units. The aims of the present study were: (1) to evaluate the accuracy of the most commonly used REE prediction formulae developed for healthy children, in children with CP; (2) to assess the accuracy of the REE population-specific formula for CP children proposed in our preliminary report; (3) to develop new population-specific methods. Methods: REE was measured by indirect calorimetry in 100 children and adolescents with spastic quadriplegic cerebral palsy (SQCP) and estimated on the basis of predictive formulas selected by the clinicians [World Health Organization (WHO), Harris-Benedict, Schofield weight, Schofield weight & height, Oxford, Mifflin formulae and a population-specific formula for CP children developed in our preliminary report]. Results: 100 children with SQCP (35 girls, 35%) classified as level V according to gross motor function classification system (GMFCS-V); 64% with oral nutrition, 29% total enteral nutrition (nasogastric tube feeding, percutaneous endoscopic gastrostomy, percutaneous endoscopic transgastric jejunostomy) and 7% mixed nutrition. The median (IQR) REE was 41.96 (17.5) kcal/kg/day.Statistical analysis highlighted a proportional bias between the indirect calorimetry and all considered predictive formulae for REE determination. By studying the relationship between the bias and the mean values of REE, specific conversion equations were obtained. With a pre-specified model having as predictors the variable weight and the variable Triceps Skinfold (TSF) and, as response the variable REE measured by indirect calorimetry, a predictive nomogram was developed to estimate the REE in this population of children. Conclusions: We suggest using predictive formulae for healthy children with caution, and where possible carrying out indirect calorimetry to assess REE in children with CP. However, we propose a new tool which could be developed to become an additional help for assessment of REE in the clinical practice.Future objectives will be to obtain a larger sample size, in a multicenter perspective study, to build a specific predictive model for the REE of the studied population.

P-DOR, an easy-to-use pipeline to reconstruct bacterial outbreaks using genomics.

SUMMARY: Bacterial Healthcare-Associated Infections (HAIs) are a major threat worldwide, which can be counteracted by establishing effective infection control measures, guided by constant surveillance and timely epidemiological investigations. Genomics is crucial in modern epidemiology but lacks standard methods and user-friendly software, accessible to users without a strong bioinformatics proficiency. To overcome these issues we developed P-DOR, a novel tool for rapid bacterial outbreak characterization. P-DOR accepts genome assemblies as input, it automatically selects a background of publicly available genomes using k-mer distances and adds it to the analysis dataset before inferring a Single-Nucleotide Polymorphism (SNP)-based phylogeny. Epidemiological clusters are identified considering the phylogenetic tree topology and SNP distances. By analyzing the SNP-distance distribution, the user can gauge the correct threshold. Patient metadata can be inputted as well, to provide a spatio-temporal representation of the outbreak. The entire pipeline is fast and scalable and can be also run on low-end computers. AVAILABILITY AND IMPLEMENTATION: P-DOR is implemented in Python3 and R and can be installed using conda environments. It is available from GitHub https://github.com/SteMIDIfactory/P-DOR under the GPL-3.0 license.

Dual biological therapy and small molecules in pediatric inflammatory bowel disease.

Inflammatory bowel diseases (IBDs) including Crohn's disease (CD), ulcerative colitis (UC) and inflammatory bowel disease unclassified (IBD-U) are chronic inflammatory disorders which can affect the gastrointestinal tract. Anti-tumor necrosis factors antibodies (anti-TNFα) such as infliximab (IFX) and adalimumab (ADA) are the first line biological therapy for severe or complicated IBDs in pediatric age. Second line therapeutic options as vedolizumab (VDZ) and ustekinumab (UST) are currently used off-label in pediatric age. Furthermore, despite optimization of biologics, a great proportion of patients may fail to respond to biologic agents (up to 30%) or lose response over the time (around 50%) hence these patients may be left without another valid therapeutic option. Consequently, several efforts have been made in the last years in order to develop new drugs and to contrive new therapeutic strategies. Small molecule drugs (SMDs) and combination therapy with either two biologic agents or with a SMD and a biological agent have recently been proposed. Data on safety and efficacy of these new therapeutic options are limited. The objective of the present review is to summarize the most up-to-date available literature in pediatric IBD.

Preschool-located influenza vaccination and influenza-like illness surveillance: an Italian pilot experience.

BACKGROUND: We describe the first school-located influenza vaccination campaign with quadrivalent live-attenuated influenza vaccine (LAIV) among pre-school children in Italy, coupled with an innovative school-centred influenza-like illnesses (ILIs) surveillance using a self-sampling non-invasive saliva collection method. METHODS: The pilot study was proposed during the 2021/2022 influenza season to fifteen pre-schools in the Milan municipality. LAIV was offered directly in school to all healthy children without contraindications. ILI differential diagnosis was conducted by real-time RT-PCR for influenza A/B and SARS-CoV-2. RESULTS: Five pre-schools were involved in the pilot project and overall, 135 families (31.2%) participated in the study, adhering to both surveillance and vaccination; 59% of families had an immigrant background. No pupil experienced adverse reactions after vaccination. Nineteen saliva samples were collected from sixteen children (11.8%). Six samples (31.6%) tested positive for SARS-CoV-2; none was positive for influenza A/B. CONCLUSIONS: The participation in the immunisation campaign was good, considering possible absences due to COVID-19 pandemic, and the intranasal administration was well tolerated and helped to overcome parental hesitancy. Saliva sampling represented a useful tool to reduce children's stress and increase parents' compliance. The high participation of families with an immigrant background suggests that school-based interventions can represent an effective strategy to overcome socioeconomic and cultural barriers.

Early-Life Nutrition in Preterm Infants and Risk of Respiratory Infections and Wheezing: A Scoping Review.

INTRODUCTION: Preterm birth is a common early-life event that can lead to long-term consequences. The incidence of wheezing, asthma, and respiratory tract infections is higher in children born prematurely than in the general population. The purpose of this review was to synthesize the existing literature on the role of early-life nutrition in the later risk of respiratory morbidities. METHODS: A scoping review of the literature was performed by searching three online databases. Inclusion criteria were: infants born <37 GWk, comparing human milk versus any other type of milk feeding formulation. Our primary outcomes were wheezing or asthma or respiratory tract infections after discharge. Two authors independently screened the results and extracted study characteristics using a predefined charting form. RESULTS: Nine articles were included (eight cohort studies and one randomized trial). Four studies supported the protective effect of breastfeeding on wheezing or respiratory infections or both. Four studies did not confirm this association. One study confirmed the protective role of breastfeeding only on the subgroup of girls. There was a high heterogeneity among the included studies, in the type of milk feeding, outcomes, and age at follow-up. CONCLUSIONS: The current evidence is conflicting. The high heterogeneity and methodological flaws could have influenced the results of the studies. Carefully designed studies are required to define the role of early-life nutrition among preterm infants on their long-term respiratory outcomes.

Invasive Group A streptococcal infections: are we facing a new outbreak? A case series with the experience of a single tertiary center.

BACKGROUND: In pediatric age, Group A Streptococcus (GAS) is responsible for a wide spectrum of clinical manifestations, from mild localized infections to life-threatening invasive diseases. In December 2022, the World Health Organization reported an increased incidence of scarlet fever and invasive GAS infections (iGAS) cases in Europe and the United States. In line with these observations, surveillance has been strengthened in our Region, allowing the identification of certified or highly suspected forms of iGAS. CASE PRESENTATION: We report here 4 emblematic cases of iGAS admitted to our Intensive Care Unit (ICU) in the short time span from mid-February to mid-March 2023. Particularly, we describe a case of pleuropneumonia (4 year old boy) and a case of respiratory failure (2 year old boy), who necessitated Non-Invasive Ventilation support, a case of Streptococcal Toxic Shock Syndrome (6 year old girl), presenting with multi-organ failure, who needed Invasive Ventilation, and a case of meningitis (5 year old girl). All these patients needed intensive care support. CONCLUSIONS: Accurate differential diagnosis and early treatment both could help to reduce the transmission of GAS and consequently the risk of severe iGAS. These cases confirmed the need for close monitoring and appropriate notification, in order to verify their actual increased incidence.

Antioxidant potential of the diet in Italian children with food allergies.

A reduced fruit and vegetable consumption, which implies a decreased intake of antioxidant compounds, seems to play a role in allergic diseases onset. Data on the antioxidant capacity of diet in children with food allergies, who are on an avoidance diet, are still lacking. This pilot study aims to assess the antioxidant potential of diet in Italian children with food allergies, compared to healthy children, using the oxygen radical absorbance capacity (ORAC) method. 95 children (54 with confirmed food allergies and 41 controls), with a median age of 7.8 years, were enrolled and underwent a nutritional assessment. Mean nutrient intakes were compared using the Mann-Whitney test. ORAC resulted significantly lower in allergic children (median 2,908, IQR: 1450;4,716) compared to control children (median 4,392, IQR: 2523;5,836; p = 0.049). Among micronutrients with antioxidant properties, vitamin A intakes were significantly higher in controls than in allergic children. Using Spearman's correlation, a moderate-to-strong correlation between ORAC and vitamin C, potassium and magnesium was observed (ρ = 0.648, p < 0.001; ρ = 0.645, p < 0.001; ρ = 0.500, p < 0.001, respectively). Iron, phosphorus, vitamin E and vitamin A intakes were also moderately-to-low correlated with ORAC values (ρ = 0.351, p < 0.001; ρ = 0.367, p < 0.001; ρ = 0.346, p < 0.001; and ρ = 0.295, p = 0.004, respectively). We hypothesize that the reduced antioxidant potential of the diet might be related to a reduced variety of the diet in children with food allergies. Our study suggests that the diet of children with food allergies has a lower antioxidant potential (expressed as ORAC value) compared to the diet of healthy children, regardless of the allergenic food excluded from the diet. This issue should be further investigated in prospective, powered studies.

The Immunological Profile of SARS-CoV-2 Infection in Children Is Linked to Clinical Severity and Age.

Coronavirus disease 19 (COVID-19) is clinically less severe in children, even if the wide variety and degree of severity of symptoms reported in children pose a still-unresolved challenge for clinicians. We performed an in-depth analysis of the immunological profiles of 18 hospitalized SARS-CoV-2-infected children, whose results were compared to those obtained from 13 age- and sex-matched healthy controls (HC). The patients were categorized as paucisymptomatic/moderate (55.6%) or severe/critical (44.5%) according to established diagnostic criteria and further stratified into the categories of infants (1-12 months), children (1-12 years), and adolescents (>12 years). We assessed SARS-CoV-2-specific RBD antibodies (Ab), neutralizing antibodies (nAb), and circulating cytokines/chemokines in the plasma, and the SARS-CoV-2-specific immune response was measured in PBMCs by gene expression and secretome analyses. Our results showed peculiar circulating cytokine/chemokine profiles among patients sharing a similar clinical phenotype. A cluster of patients consisting of infants with severe symptoms presented hyperinflammatory profiles, together with extremely polarized antibody profiles. In a second cluster consisting of paucisymptomatic patients, a less pronounced increase in the level of inflammatory cytokines, together with an association between the selected cytokines and humoral responses, was observed. A third cluster, again consisting of paucisymptomatic patients, showed a circulating cytokine/chemokine profile which overlapped with that of the HC. The SARS-CoV-2-stimulated production of pro-inflammatory proteins, T lymphocyte activation, and migration-specific proteins, were significantly increased in SARS-CoV-2-infected children compared to the HC. Our findings suggest that immune response activation in the course of SARS-CoV-2 infection in children is directly correlated with clinical severity and, to a lesser extent, age.

Head-to-head comparison of four COVID-19 vaccines on platelet activation, coagulation and inflammation. The TREASURE study.

INTRODUCTION: Studies exploring alterations in blood coagulation and platelet activation induced by COVID-19 vaccines are not concordant. We aimed to assess the impact of four COVID-19 vaccines on platelet activation, coagulation, and inflammation considering also the immunization dose and the history of SARS-CoV-2 infection. METHODS: TREASURE study enrolled 368 consecutive subjects (161 receiving viral vector vaccines -ChAdOx1-S/Vaxzevria or Janssen- and 207 receiving mRNA vaccines -Comirnaty/Pfizer-BioNTech or Spikevax/Moderna). Blood was collected the day before and 8 ± 2 days after the vaccination. Platelet activation markers (P-selectin, aGPIIbIIIa and Tissue Factor expression; number of platelet-monocyte and -granulocyte aggregates) and microvesicle release were analyzed by flow cytometry. Platelet thrombin generation (TG) capacity was measured using the Calibrated Automated Thrombogram. Plasma coagulation and inflammation markers and immune response were evaluated by ELISA. RESULTS: Vaccination did not induce platelet activation and microvesicle release. IL-6 and CRP levels (+30%), D-dimer, fibrinogen and F1+2 (+13%, +3.7%, +4.3%, respectively) but not TAT levels significantly increased upon immunization with all four vaccines, with no difference among them and between first and second dose. An overall minor post-vaccination reduction of aPC, TM and TFPI, all possibly related to endothelial function, was observed. No anti-PF4 seroconversion was observed. CONCLUSION: This study showed that the four COVID-19 vaccines administered to a large population sample induce a transient inflammatory response, with no onset of platelet activation. The minor changes in clotting activation and endothelial function might be potentially involved at a population level in explaining the very rare venous thromboembolic complications of COVID-19 vaccination.

An Unusual Retained Choanal Foreign Body: A Possible Complication of COVID-19 Testing With Nasopharyngeal Swab.

Testing for coronavirus disease 2019 is critical in controlling the pandemic all over the world. Diagnosis of severe acute respiratory syndrome coronavirus-2 infection is based on real-time polymerase chain reaction performed on nasopharyngeal swab. If not adequately performed, the viral specimen collection can be painful and lead to complications. We present a complication occurred during a nasopharyngeal swab collection performed in a noncooperative patient where the plastic shaft of the swab fractured during the procedure, resulting in swab tip retention deep into the nasal cavity. The foreign body was found endoscopically, stuck between the nasal septum and the superior turbinate tail at the upper level of the left choana and removed under general anesthesia in a negative pressure operating room with the health care personnel wearing personal protective equipment. Unpleasant complications like the one described can happen when the swab is collected without the necessary knowledge of nasal anatomy or conducted inappropriately, especially in noncooperative patients. Moreover, the design of currently used viral swabs may expose to accidental rupture, with risk of foreign body retention in the nasal cavities. In such cases, diagnosis and treatment are endoscopy-guided procedures performed in an adequate setting to minimize the risk of spreading of the pandemic.

Surface Cranial Ultrasound: The Natural Heir to X-Ray for the Screening of Skull Deformities in Infants.

PURPOSE: Volumetric tomography (3D-CT) is currently considered the gold standard for the diagnosis of craniosynostosis, but its use as the first-line examination for cranial deformities is a topic of debate, because of skull X-ray radiation and low sensitivity and specificity. Cranial ultrasound is an emerging noninvasive radiation-free alternative, but its diagnostic accuracy still needs confirmation. MATERIALS AND METHODS: The present prospective study included 350 infants with skull deformities, who underwent cranial ultrasound as the first-line examination, followed by 3D-CT if the echography results was positive or unclear. If the results were negative, infants underwent physical treatment and follow-up. To evaluate ultrasound reliability, we focused on cases that underwent both the index test and the gold standard and performed a double-blind comparison of the echography and 3D-CT results. RESULTS: Ultrasound documented patent sutures in 293 infants and 9 had inconclusive results. The 293 ultrasound-negative infants were followed clinically: all improved, except 28 that underwent 3D-CT. In all of these cases, 3D-CT confirmed the ultrasonography results (no false negatives). 48 infants showed premature suture closure and underwent 3D-CT: 47 were confirmed (true positive), 1 was false positive. The sensitivity was 100%, the specificity was 99.7%, the positive and negative predictive values were 97.9% and 100%, respectively, the accuracy was 99.7%, and the diagnostic test evaluation was conclusive. CONCLUSION: The study documented the high sensitivity and specificity of echography for the diagnosis of craniosynostosis in a referral center, with better results being achieved before 6 months of age. Major limitations are the loss of diagnostic significance as the child grows and the learning curve needed. The advantages are avoidance of radiation and chance to evaluate the brain at the same time.