Neonatal diagnosis of primary ciliary dyskinesia in a high consanguinity population: a single tertiary center experience.

Though PCD usually presents after birth in term neonates, diagnosing PCD during the neonatal and infancy stages is uncommon, particularly in children who do not exhibit laterality defects. We report our recent experience with the diagnosis of PCD in the neonatal and early infantile period in a highly consanguine population. This was achieved by implementing a novel genetic-based diagnostic approach based on direct testing for recognized regional genetic variants. We conducted a retrospective analysis of children diagnosed with PCD at Soroka University Medical Center during the neonatal or early infantile period between 2020 and 2023. We included children under 3 months of age who had a genetic confirmation of PCD, as evidenced by the presence of two pathogenic variants in recognized genes. Genetic testing targeted regional genetic variants in previously identified PCD genes. Eight patients were included. The median age at diagnosis was 12.5 days. Three (38%) were born prematurely < 34 weeks gestational age. All patients were presented with respiratory distress and hypoxemia after birth. The median duration of oxygen support was 23 days, and upper lobe atelectasis was present in five patients (63%). Congenital cardiac malformation was present in four patients. Organ laterality defects were present in four patients. Genetic mutations identified were in the DNAAF5, DNAL1, DNAAF3, and DNAH1 genes.     Conclusion: Neonatal diagnosis of PCD is uncommon, especially in atypical presentations such as children without laterality defects or preterms. Focusing on a genetic diagnosis of the local tribal pathogenic variants promotes a potential cost-efficient test leading to earlier diagnosis. There is a need for a standardized protocol for earlier diagnosis of PCD in high-consanguinity areas. What is Known: • Primary ciliary dyskinesia (PCD) typically presents after birth in term neonates. • Diagnosing PCD during neonatal and infancy stages is challenging, particularly in children without laterality defects. What is New: • A novel genetic-based diagnostic approach was implemented on the neonatal population in a highly consanguine community, focusing on direct testing for regional genetic variants, leading to early and rapid diagnosis of PCD.

Diagnostic Yield of Critical Sample and Elective Fast-Test in Children After a Hypoglycemic Event: Experience From a Single Center in Israel.

OBJECTIVE: To determine the diagnostic yield of the critical sample and fast-tests as dynamic function tests for the work-up of hypoglycemia in children. METHODS: A retrospective record review of children (0-18 years) with a diagnosis of hypoglycemia (glucose ≤ 50 mg/dL) was performed. A comparison of results of critical sample (obtained during an episode of hypoglycemia) and fast-test (performed to induce hypoglycemia in fasting state) was done. RESULTS: In 317 patients with hypoglycemia, data of 89 critical samples and 52 fast-tests were taken. Only 7 (7.8%) patients who underwent critical sample testing received an endocrine or metabolic diagnosis. No confirmatory diagnoses were made using the fast-tests. Idiopathic ketotic hypoglycemia was detected in 33/89 (37.1%) of critical samples and 21/52 (40.4%) of fast-tests. The completeness of workup including the hormonal and metabolic profile was <80% in both tests. CONCLUSION: The confirmatory yield of critical sample was better than fast-test. The processing of metabolic analytes was incomplete in a few, suggesting the need to rationalize the dynamic function testing.

Circadian immunity from bench to bedside: a practical guide.

The immune system is built to counteract unpredictable threats, yet it relies on predictable cycles of activity to function properly. Daily rhythms in immune function are an expanding area of study, and many originate from a genetically based timekeeping mechanism known as the circadian clock. The challenge is how to harness these biological rhythms to improve medical interventions. Here, we review recent literature documenting how circadian clocks organize fundamental innate and adaptive immune activities, the immunologic consequences of circadian rhythm and sleep disruption, and persisting knowledge gaps in the field. We then consider the evidence linking circadian rhythms to vaccination, an important clinical realization of immune function. Finally, we discuss practical steps to translate circadian immunity to the patient's bedside.

Stepwise genetic approach for the diagnosis of primary ciliary dyskinesia in highly consanguineous populations.

BACKGROUND: The American Thoracic Society guidelines for the diagnosis of primary ciliary dyskinesia (PCD) consider the presence of a bi-allelic pathogenic variant confirmatory for the diagnosis of PCD, with genetic testing recommended when other confirmatory diagnostic tests are less accessible. We present our experience with genetic testing as first line with a proposed algorithm for high consanguinity populations. METHODS: Patients with a suspected diagnosis of PCD underwent genetic testing according to a diagnostic algorithm composed of three steps: (1) patients with a previously known causative familial/Bedouin tribal pathogenic variant completed direct testing for a single variant; (2) if the initial test was negative or there was no known pathogenic variant, a PCD genetic panel was completed; (3) if the panel was negative, whole exome sequencing (WES) was completed. RESULTS: Since the implementation of the protocol, diagnosis was confirmed by genetic testing in 21 patients. The majority of them were of Bedouin origin (81%) and had a positive history of consanguinity (65%). Nine patients (43%) had a sibling with a confirmed diagnosis. Most patients (15/21, 71%) were diagnosed by direct pathogenic variant testing and the remainder by genetic panel (19%) and WES (10%). Disease-causing variants were found in nine genes, with DNAL1 (24%) and DNAAF3, DNAAF5, ZMYND10 (14% each) as the most prevalent ones. CONCLUSIONS: In highly consanguineous regions, a stepwise genetic testing approach is recommended. This approach may be particularly useful in areas where the ability to obtain confirmatory diagnostic tests through other modalities is less accessible.

Eradication of Nontuberculous Mycobacteria in People with Cystic Fibrosis Treated with Elexacaftor/Tezacaftor/Ivacaftor: A Multicenter Cohort Study.

BACKGROUND: The prevalence of nontuberculous mycobacteria (NTM) infections is rising in people with cystic fibrosis (pwCF). NTM infection, especially infection with Mycobacterium abscessus complex (MABC), is commonly associated with severe lung deterioration. The current treatment modalities, including multiple intravenous antibiotics, frequently fail to achieve airway eradication. Although treatment with elexacaftor/tezacaftor/ivacaftor (ETI) has been shown to modulate the lung microbiome, data regarding its role in eradicating NTM in pwCF is lacking. Our aim was to evaluate the impact of ETI on the rate of NTM eradication in pwCF. METHODS: This retrospective multicenter cohort study included pwCF from five CF centers in Israel. PwCF aged older than 6 who had at least one positive NTM airway culture in the past two years and were treated with ETI for at least one year were included. The annual NTM and bacterial isolations, pulmonary function tests, and body mass index were analyzed before and after ETI treatment. RESULTS: Fifteen pwCF were included (median age 20.9 years, 73.3% females, 80% pancreatic insufficient). In nine patients (66%) NTM isolations were eradicated following treatment with ETI. Seven of them had MABC. The median time between the first NTM isolation and treatment with ETI was 2.71 years (0.27-10.35 years). Eradication of NTM was associated with improved pulmonary function tests (p<0.05). CONCLUSIONS: For the first time, we report successful eradication of NTM, including MABC, following treatment with ETI in pwCF. Additional studies are needed to assess whether treatment with ETI can result in the long-term eradication of NTM.

The impact of maternal hyperemesis gravidarum on early childhood respiratory morbidity.

BACKGROUND: Lung maldevelopment due to in-utero events may potentially cause respiratory morbidity during childhood. Maternal nutritional status during pregnancy is critical for lung development. This study is contributing to the understanding of the interplay between maternal nutrition status during pregnancy, fetal lung development and the risk for respiratory diseases in early life. RESEARCH QUESTION: To investigate the association between maternal hyperemesis gravidarum (HG) during pregnancy and respiratory morbidity in the offspring's early childhood. STUDY DESIGN AND METHODS: This is a retrospective population-based cohort study that included all singleton term deliveries at Soroka University Medical Center (SUMC) between 1991 and 2021. Preterm deliveries (<37 gestational week), perinatal deaths, multiple gestations, and children with congenital malformations or chromosomal abnormalities were excluded. The main outcomes measured were offspring's hospitalizations due to pneumonia, acute bronchiolitis, asthma, or wheezing. RESULTS: Overall 232,476 deliveries were included in the study, of which 3227 women (1.4%) were diagnosed with HG. Offspring in the HG group exhibited significantly higher rates of respiratory morbidity, including asthma (OR = 1.36, 95% CI 1.22-1.36, p < .001), acute bronchiolitis (OR = 1.38, 95% CI 1.21-1.59, p < .001), and pneumonia (OR = 1.2, 95% CI 1.12-1.48, p < .001). An inverse correlation between multivariate adjusted-hazard ratios for asthma and pneumonia with offspring's age was noted. INTERPRETATION: This study provides evidence of a potential association between maternal HG during pregnancy and increased risk of respiratory morbidity in offspring's early childhood. Maternal nutritional status during pregnancy plays a crucial role in lung development, affecting respiratory health in childhood.

Comparing single versus multiple virus detection in pediatric acute gastroenteritis postimplementation of routine multiplex RT-PCR diagnostic testing.

Utilizing multiplex real time polymerase chain reaction (RT-PCR) for rapid diagnosis of gastroenteritis, enables simultaneous detection of multiple pathogens. A comparative analysis of disease characteristics was conducted between cases with single and multiple viruses. Rotavirus vaccine was introduced in 2010, reaching a 70% coverage in 2 years. All rectal swabs collected from diarrheic children (<5 years) between December 2017 and March 2022 were included. Detection of the same viruses within 2 months was considered a single episode. Episodes with positive stool bacterial PCR were excluded. A total of 5879 samples were collected, revealing 86.9% (1509) with single virus detection and 13.1% (227) with multiple viruses. The most frequent combination was rotavirus and norovirus (27.8%), these infections followed a winter-spring seasonality akin to rotavirus. Children with multivirus infections exhibited higher immunodeficiency (OR 2.06) rates, but lower food allergy (OR 0.45) and prematurity rates (OR 0.55) compared to single infections. Greater disease severity, evaluated by the Vesikari score, was observed in multivirus episodes (p < 0.001, OR 1.12). Multivirus infections accounted for 13.1% of symptomatic cases in hospitalized young children. Despite vaccination efforts, rotavirus remained prominent, frequently in co-infections with norovirus. Overall, multivirus infections were linked to more severe diseases than single virus cases.

Implementing a multiplex-PCR test for the diagnosis of acute gastroenteritis in hospitalized children: Are all enteric viruses the same?

BACKGROUND: Multiplex-PCR is a valuable tool for diagnosing viral acute gastroenteritis (AGE), enabling the detection of multiple pathogens. However, distinguishing between active disease and shedding poses challenges. This study aimed to evaluate viral AGE epidemiology and compare clinical characteristics among the five most common viruses. METHODS: Rotavirus vaccine was introduced in 2010, with 70% coverage achieved in southern Israel in two years. All rectal swabs for multiplex-PCR targeting rotavirus, norovirus, adenovirus, astrovirus and sapovirus from hospitalized diarrheic children <5 years were included, from December 2017 through March 2022. Detection of the same virus within two months was considered a single episode. Clinical analysis included episodes with single-virus detection and negative bacterial PCR. RESULTS: Among 5,879 rectal swabs, 2,662 (45.3%) tested positive for at least one virus, with 245 (9.2%) showing multiple virus detection. Rotavirus was the most prevalent. While rotavirus exhibited typical winter-spring seasonality in 2018-19, an unusual off-season surge was observed during the second year of the COVID-19 pandemic. Among negative bacterial PCR episodes, 34.6% had mucus stool, 5.9% had bloody stool, and 29.3% received antibiotics. Astrovirus or sapovirus infections were associated with higher rates of hospital-acquired AGE and immunodeficiency (P<0.05), whereas rotavirus infections had higher rates of dehydration severity and acute kidney injury (P<0.05). DISCUSSION: Enteric viruses were detected in 45.3% of rectal swabs from hospitalized children with diarrhea. Despite vaccination efforts, rotavirus remained prevalent and caused more severe disease. Continuous surveillance using multiplex-PCR is crucial for accurate management and future prevention strategies for viral AGE.

The role of anion gap normalization time in the management of pediatric diabetic ketoacidosis.

Introduction: Our aims were to determine whether anion gap normalization time (AGNT) correlates with risk factors related to the severity of diabetic ketoacidosis (DKA) in children, and to characterize AGNT as a criterion for DKA resolution in children admitted with moderate or severe disease. Methods: A ten-year retrospective cohort study of children admitted to the intensive care unit with DKA. We used a survival analysis approach to determine changes in serum glucose, bicarbonate, pH, and anion gap following admission. Using multivariate analysis, we examined associations between patients' demographic and laboratory characteristics with delayed normalization of the anion gap. Results: A total of 95 patients were analyzed. The median AGNT was 8 h. Delayed AGNT (>8 h) correlated with pH < 7.1 and serum glucose >500 mg/dL. In multivariate analysis, glucose >500 mg/dL was associated with an increased risk for delayed AGNT, by 3.41 fold. Each 25 mg/dL elevation in glucose was associated with a 10% increment in risk for delayed AGNT. Median AGNT preceded median PICU discharge by 15 h (8 vs. 23 h). Discussion: AGNT represents a return to normal glucose-based physiology and an improvement in dehydration. The correlation observed between delayed AGNT and markers of DKA severity supports the usefulness of AGNT for assessing DKA recovery.

Biological rhythms in COVID-19 vaccine effectiveness in an observational cohort study of 1.5 million patients.

BACKGROUNDCircadian rhythms are evident in basic immune processes, but it is unclear if rhythms exist in clinical endpoints like vaccine protection. Here, we examined associations between COVID-19 vaccination timing and effectiveness.METHODSWe retrospectively analyzed a large Israeli cohort with timestamped COVID-19 vaccinations (n = 1,515,754 patients over 12 years old, 99.2% receiving BNT162b2). Endpoints included COVID-19 breakthrough infection and COVID-19-associated emergency department visits and hospitalizations. Our main comparison was among patients vaccinated during morning (800-1159 hours), afternoon (1200-1559 hours), or evening hours (1600-1959 hours). We employed Cox regression to adjust for differences in age, sex, and comorbidities.RESULTSBreakthrough infections differed based on vaccination time, with lowest the rates associated with late morning to early afternoon and highest rates associated with evening vaccination. Vaccination timing remained significant after adjustment for patient age, sex, and comorbidities. Results were consistent in patients who received the basic 2-dose series and who received booster doses. The relationship between COVID-19 immunization time and breakthrough infections was sinusoidal, consistent with a biological rhythm that modifies vaccine effectiveness by 8.6%-25%. The benefits of daytime vaccination were concentrated in younger (<20 years old) and older patients (>50 years old). COVID-19-related hospitalizations varied significantly with the timing of the second booster dose, an intervention reserved for older and immunosuppressed patients (HR = 0.64, morning vs. evening; 95% CI, 0.43-0.97; P = 0.038).CONCLUSIONWe report a significant association between the time of COVID-19 vaccination and its effectiveness. This has implications for mass vaccination programs.FUNDINGNIH.

Age-dependent rebound in asthma exacerbations after COVID-19 lockdown.

Background: Virus mitigation measures enacted early in the coronavirus infectious disease 2019 (COVID-19) pandemic suppressed common respiratory viruses and reduced the number of obstructive lung disease exacerbations. However, many localities began to ease these precautions in the year 2021, leading to a resurgence of non-COVID viruses. How asthma and chronic obstructive pulmonary disease (COPD) activity responded to this upswing in viral abundance is unclear. Objective: Our aim was to examine how viral resurgence during the relaxation of COVID-19 restrictions affected asthma and COPD exacerbations. Methods: We analyzed electronic medical records for emergency department (ED) respiratory virus positivity, asthma visits, and COPD visits. We compared the 52-week interval before the COVID-19 restrictions (the pre-lockdown period [March 22, 2019-March 19, 2020]), the 52-week period immediately following enactment of the restrictions (the lockdown period [March 20, 2020-March 18, 2021]), and the 52-week period thereafter (the post-lockdown period [March 19, 2021-March 18, 2022]). We used MetaCYCLE to analyze seasonal trends in our data. Results: The post-lockdown period was marked by a 400% increase in viral positivity compared with during the lockdown period. Asthma- and COPD-related ED visits each rose 37% compared with during the lockdown, with the rebound in asthma ED visits concentrated in individuals younger than 20 years. Interestingly, after the lockdown period, asthma ED visits overcorrected in children younger than 5 years, rising 81% compared with before the lockdown. Seasonal rhythms in asthma and COPD exacerbations were suppressed during the lockdown and recovered after the lockdown. Conclusions: COVID-19 precautions had the unexpected effect of magnifying early-childhood asthma activity once common respiratory viruses recurred. These results may have implications for the future use of virus mitigation strategies in young children.

Markers for severe disease and long-term sequelae in pediatric patients with severe acute respiratory syndrome coronavirus 2 infection.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has resulted in substantial global morbidity and mortality since late 2019. Children can be infected but the disease predominantly affects adults, and research into the acute and chronic sequelae mostly pertains to this population. This study determines the clinical and demographic parameters associated with severe acute disease and chronic complications from COVID-19 in the pediatric population. METHODS: A retrospective chart review was undertaken of all patients between birth and 21 years of age who were positive for SARS-CoV-2 by polymerase chain reaction (PCR) and were admitted to two tertiary care hospitals between March 1, 2020, and January 21, 2021. Markers for severe disease were defined as supplemental oxygen requirement, positive pressure ventilation, and acute chest radiograph abnormality at presentation. Chronic disease was defined as symptoms persisting >4 weeks. RESULTS: Review of 101 patients with positive SARS-CoV2 testing found 67 presentations consistent with acute symptomatic infection. Age distribution was bimodal, with predominance in infancy and adolescence. Most (75%) had an extrapulmonary comorbidity, and fewer patients (33%) had pre-existing lung disease. A history of pulmonary comorbidity and obesity was significantly associated with markers for severe disease. Long-term chronic complications were associated with history of underlying lung disease and acute severe COVID-19. CONCLUSIONS: Demographic and clinical markers were associated with severe COVID-19 in children. Moreover, both the presence of pulmonary comorbidity and severe acute COVID-19 are associated with long-term sequelae.

Delayed Neuropsychiatric Sequel Following Pediatric Carbon Monoxide Poisoning: A Case Report and Literature Review.

Carbon monoxide (CO) poisoning is a serious health problem. The main pathophysiological mechanism of acute CO poisoning is hypoxia due to the formation of carboxyhemoglobin (COHb). Delayed neuropsychiatric sequel (DNPS) occurs following an interval of several days to several weeks post-CO exposure and can present in many different manifestations, ranging from behavioral and mood disorders to encephalopathy and seizures and cause long-term neuropsychiatric sequel. The pathogenesis of DNPS following CO poisoning is a complex one that encompasses hypoxia-induced encephalopathy as well as inflammation, direct cellular changes and damage. The incidence varies and treatment is debated. We display a case of a previously healthy 13-year-old boy suffering from DNPS, presenting with seizures and encephalopathy and later developing optic nerve damage. Increased awareness to this condition might help diagnose future patients and aid in the understanding of the pathogenesis and treatment options for this poorly understood condition.

Effect of the COVID-19 Lockdown on Asthma Biological Rhythms.

Asthma has a striking temporal character, in which time-of-day, patient age, and season each influence disease activity. The extent to which rhythms in asthma activity reflect exposure to specific disease triggers remains unclear. In this study, we examined how virus mitigation strategies enacted during the COVID-19 pandemic ("lockdown measures") affected rhythms in asthma clinical activity in children. To this end, we retrospectively analyzed asthma clinical presentations in children aged <18 years to our regional academic medical center, comparing 4 years of medical records prior to COVID-19 lockdown measures with the 12 months immediately after the institution of such measures. We correlated these data to positive viral test results, febrile seizures, and allergic clinical surrogates (allergic reaction visits and Emergency Department [ED] antihistamine prescriptions, respectively) over the same time frame. In the 12 months following the institution of the COVID-19 lockdown, positivity rates for common respiratory viruses dropped by 70.2% and ED visits for asthma among children dropped by 62% compared to pre-COVID years. Lockdown suppressed seasonal variation in positive viral tests and asthma ED visits, while diurnal rhythms in asthma visits were unchanged. Asthma seasonality correlated most strongly with rhinovirus positivity both before and after the institution of COVID lockdown measures. Altogether, our data support a causal role for viruses in driving seasonal variability in asthma exacerbations in children.

Age-Dependent Reduction in Asthmatic Pathology through Reprogramming of Postviral Inflammatory Responses.

Asthma is a chronic disease of childhood, but for unknown reasons, disease activity sometimes subsides as children mature. In this study, we present clinical and animal model evidence suggesting that the age dependency of childhood asthma stems from an evolving host response to respiratory viral infection. Using clinical data, we show that societal suppression of respiratory virus transmission during coronavirus disease 2019 lockdown disrupted the traditional age gradient in pediatric asthma exacerbations, connecting the phenomenon of asthma remission to virus exposure. In mice, we show that asthmatic lung pathology triggered by Sendai virus (SeV) or influenza A virus is highly age-sensitive: robust in juvenile mice (4-6 wk old) but attenuated in mature mice (>3 mo old). Interestingly, allergen induction of the same asthmatic traits was less dependent on chronological age than viruses. Age-specific responses to SeV included a juvenile bias toward type 2 airway inflammation that emerged early in infection, whereas mature mice exhibited a more restricted bronchiolar distribution of infection that produced a distinct type 2 low inflammatory cytokine profile. In the basal state, aging produced changes to lung leukocyte burden, including the number and transcriptional landscape of alveolar macrophages (AMs). Importantly, depleting AMs in mature mice restored post-SeV pathology to juvenile levels. Thus, aging influences chronic outcomes of respiratory viral infection through regulation of the AM compartment and type 2 inflammatory responses to viruses. Our data provide insight into how asthma remission might develop in children.

The effects of the COVID-19 pandemic on patients with lysosomal storage disorders in Israel.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) is the causative agent of the current COVID-19 pandemic. Lysosomal storage disorders (LSD) comprise of 70 inherited inborn errors of metabolism. Affected individuals suffer from multi-systemic involvement with variable severity and rate of disease progression between different diseases. Some of the LSDs have established treatments, whether parenteral or oral therapies. The full impact of the COVID-19 pandemic together with the lockdown on the wellbeing and medical management of patients with rare diseases, such as LSDs, is widely unknown. Herein, we describe the effects of the COVID-19 pandemic and its associated mandatory home lockdown on patients with LSDs in Israel. RESULTS: We present a prospective multi-center questionnaire study including 48 LSD patients from four medical centers in Israel. The study objective was to assess the impact of the COVID-19 pandemic restrictions on individuals with LSDs in Israel, as reported by their caregivers. Secondary objectives were to assess the morbidity from SARS CoV-2 in LSD patients and the impact of changes in mood and behavior on compliance to treatment and to assess the relationship between changes in mood to changes in cognition and behavior. Thirty one of 38 patients (82%) who received any kind of regular treatment did not miss treatments. Among patients receiving enzyme replacement therapy (ERT) in the in-hospital setting, 5 patients (20%) experienced treatment disruptions. Four patients had tested positive for SARS-Cov-2 virus infection by PCR. Seven out of the 48 patients (14%) described mood changes with cognitive and motor deterioration during the home quarantine. CONCLUSIONS: We observed high rates of treatment adherence and low morbidity through the COVID-19 pandemic in patients with LSDs in Israel. LSDs patients can be a model for patients with complex chronic diseases requiring routine treatments and surveillance during a pandemic or other disruption of daily routine.

Comparison of septic and nonseptic pulmonary embolism in children.

BACKGROUND: Septic pulmonary embolism (SPE) in children is a rare disease. Data are scarce regarding the clinical and laboratory manifestation of SPE compared with nonseptic pulmonary embolism (ns-PE). Furthermore, specific guidelines for the management of SPE in children are lacking. AIM: We compared the clinical course and outcome of children with SPE and ns-PE. METHODS: A retrospective, cohort study of hospitalized children, 2005-2020, with documented pulmonary embolism imaging. RESULTS: Sixteen children (eight SPE, eight ns-PE) were identified. Episodes of SPE occurred secondary to endocarditis, musculoskeletal and soft tissue infections, with Staphylococcus aureus (n = 4) and streptococcus spp. (n = 2) as the most common pathogens. Radiographically, SPE presented as a microvascular disease with parenchymatic nodules/cavitations, whereas ns-PE presented as larger vessel disease with filling defects. Risk factors (including thrombophilia) were noted in 0% and 87.5% of SPE and ns-PE patients, respectively (p < .01). Pulmonary embolism diagnosis was delayed in SPE compared with ns-PE (median: 8.5 days vs. 1 day). The SPE group had higher rates of fever (100% vs. 12.5%, p < .01), C-reactive protein (CRP levels; 18.49 vs. 4.37 mg/dl, p = .02), and fibrinogen levels (880 vs. 467 mg/dl, p < .001). Antithrombotic treatment for >4 months was administrated to 14.3% and 87.5% of SPE and ns-PE patients, respectively (p < .01). One ns-PE patient had a second thromboembolic event compared to none in the SPE group. CONCLUSIONS: SPE in children is a unique subgroup of PE with different clinical and laboratory findings that requires a different diagnostic approach and probably shorter duration of antithrombotic treatment.