BACKGROUND:Staphylococcus aureus bacteremia is associated with high mortality. Whether cefazolin or an antistaphylococcal penicillin should be preferred for the treatment of methicillin-susceptible S. aureus bacteremia is unclear. METHODS:In an ongoing international Bayesian adaptive platform trial, we conducted an open-label, randomized comparison of cefazolin with an antistaphylococcal penicillin (flucloxacillin or cloxacillin) in adult patients with penicillin-resistant, methicillin-susceptible S. aureus bacteremia. The primary outcome, which was evaluated with a hierarchical Bayesian logistic-regression model, was death from any cause within 90 days after enrollment in the platform. We assessed the posterior probability of the noninferiority of cefazolin to flucloxacillin or cloxacillin (with the criterion for noninferiority prespecified as an adjusted odds ratio of <1.2, which approximates an absolute difference in mortality of <2.5 percentage points if mortality in the antistaphylococcal-penicillin group is 15%), as well as the posterior probability of superiority (with the criterion of an adjusted odds ratio of <1.0). Secondary safety outcomes included the development of acute kidney injury within 14 days. RESULTS:This domain of the ongoing trial was conducted between February 17, 2022, and August 7, 2024, by which time the criterion for noninferiority had been met. Mortality at 90 days among adults who could be evaluated was 15.0% (97 deaths among 645 patients) in the cefazolin group and 17.0% (109 deaths among 642 patients) in the antistaphylococcal-penicillin group (adjusted odds ratio, 0.81; 95% credible interval, 0.59 to 1.12; probability of noninferiority, 99.2%; probability of superiority, 89.8%). Acute kidney injury occurred in 92 of 660 patients (13.9%) in the cefazolin group, as compared with 127 of 648 (19.6%) in the antistaphylococcal-penicillin group (adjusted odds ratio, 0.67; 95% credible interval, 0.50 to 0.89; probability of superiority, 99.7%). CONCLUSIONS:In patients with methicillin-susceptible S. aureus bacteremia, cefazolin was noninferior to flucloxacillin or cloxacillin with respect to 90-day mortality and was associated with a lower incidence of acute kidney injury. (Funded by the National Health and Medical Research Council and others; SNAP ClinicalTrials.gov number, NCT05137119.).

Nitrous oxide (N2O) is a common recreational drug. Chronic use inactivates vitamin B12 resulting in neurological damage. Most studies have focused on adults. This study aims to describe unique features of N2O-related myeloneuropathy in adolescents. Adolescents aged 14–18 years admitted with N2O-related myeloneuropathy to three tertiary medical centers in 2024 were enrolled. Their medical records were reviewed retrospectively. A systematic review was conducted for N2O-related neurologic complications in adolescents, using Embase, MEDLINE, Scopus and PubMed databases. Clinical data from the case series and systematic review were extracted and analyzed together. Five new and 54 reported patients (2011–2026) were included. All presented with neurological complaints, predominantly sensory. Vitamin B12 deficiency was detected in 45

INTRODUCTION:Supraglottitis is an acute inflammation of the epiglottis and entire supraglottic structures, and a potential cause of upper airway obstruction in children. However, data on pediatric supraglottitis remain very limited. This study aims to describe the epidemiological, clinical, laboratory, and microbiological characteristics of pediatric supraglottitis, with particular emphasis on identifying its various etiologies. STUDY DESIGN:We conducted a retrospective review of medical records of children admitted to the pediatric intensive care unit of a tertiary pediatric hospital with a diagnosis of supraglottitis, between 2004 and 2024. Patients were subsequently categorized into two groups: with adenovirus-associated supraglottitis and supraglottitis attributable to other etiologies. RESULTS:A total of 32 children with supraglottitis were included. The incidence increased by 330% between the first and second decades of the study. The most common presenting features were fever, stridor, and dyspnea. Invasive mechanical ventilation was required for 53% of patients, while 9% received noninvasive ventilation. A viral etiology was identified in 19/30 (63%) patients, with adenovirus being the most frequently detected pathogen (10 of 19 cases). Bacterial pathogens were isolated from sputum cultures in 16/17 patients, most commonly Streptococcus group A. Children with adenovirus-associated supraglottitis had significantly higher fever and C-reactive protein levels. CONCLUSIONS:In this pediatric supraglottitis cohort, incidence increased over time. Respiratory viral infections were evident in most cases, with adenovirus identified as the most common pathogen.

BACKGROUND:Fever of unknown origin (FUO) in pediatric patients remains a persistent diagnostic challenge, despite advances in imaging and laboratory techniques. Although positron emission tomography/computed tomography (PET/CT) has demonstrated substantial diagnostic value in adult populations, its utility in pediatric FUO is less clearly defined. This study aimed to assess the contribution of PET/CT to the diagnosis of FUO in hospitalized children and identify predictive clinical and laboratory factors for its diagnostic utility. METHODS:This retrospective cohort study reviewed medical records of pediatric patients (aged 0-18 years) diagnosed with FUO who underwent fluorodeoxyglucose PET/CT imaging between 2010 and 2022, at 3 medical centers in Israel. Clinical presentations, laboratory findings, and final diagnoses were compared between cases where PET/CT contributed to diagnosis or did not. RESULTS:A total of 112 patients were included. PET/CT contributed to diagnosis in 51 (45.5%) cases. Among these, infectious etiologies predominated (54.9%). In contrast, among noncontributory PET/CT cases, rheumatologic diseases were more common (66.6%). Factors associated with higher diagnostic yield included immunodeficiency, low hemoglobin, elevated lactate dehydrogenase, and low serum albumin. Conversely, presence of rash or arthritis was more common in nondiagnostic cases. PET/CT influenced treatment decisions in 40 (35.7%) patients. No significant differences in inflammatory markers levels (C-reactive protein, erythrocyte sedimentation rate, ferritin) were observed between the groups. CONCLUSIONS:PET/CT demonstrates a substantial diagnostic yield in pediatric FUO, particularly when certain predictive clinical and laboratory factors are present. It may represent a useful tool in the evaluation of unresolved cases after conventional investigations had failed to identify the cause of fever.

Respiratory tract infections (RTIs) are a leading cause of pediatric hospitalization. Although multiple concurrent viral infections are frequently detected, their impact on clinical outcomes remains unclear. This study evaluated whether viral co-infection in children leads to worse clinical outcomes, higher inflammatory markers, or increased medical management compared to single-virus infections. We retrospectively studied children aged 0–18 years hospitalized with RTIs at a tertiary pediatric center (2017–2024). Inclusion required at least one virus detected by multiplex polymerase chain reaction (PCR). Clinical, laboratory, and hospitalization data were compared between children with single versus multiple viral infections. Multivariable regression models adjusted for age, sex, and season were used to assess associations with clinical outcomes. Of 5,703 hospitalized children, 1,120 (19.6

Migratory arthritis is classically associated with acute rheumatic fever (ARF), but may signify other medical conditions. We aimed to track the final diagnoses of this obscure presentation, and to distinguish clinical variables that differentiate ARF from other conditions in order to facilitate the clinical diagnosis of ARF. Medical records were reviewed of all the patients aged 0–18 years who presented with migratory arthritis during 2015–2023 at the emergency department, pediatric wards, and the rheumatology unit of a large tertiary medical center. Primary diagnoses, demographic, clinical, and laboratory parameters were extracted and compared between patients with ARF and those with other diagnoses. A total of 101 patients with migratory arthritis were identified. Of them, 50 (49.5

Pseudotumor cerebri (PTC) is a relatively common cause of headaches in children. In order to exclude secondary causes, an extensive laboratory workup is generally recommended. This assessment causes blood loss, discomfort and a financial burden. To our knowledge, the diagnostic significance of such workup is unclear. We aimed to evaluate the clinical yield of PTC laboratory workup in a pediatric tertiary medical center. This is a retrospective study in a tertiary pediatric hospital. Included were children hospitalized between 2010–2020 with new diagnosis of definite PTC, as confirmed by a certified pediatrician and ophthalmologist. Abnormal results were reviewed by two pediatricians for clinical significance. 75 children (58.7

Background Morbidities related to obesity are usually associated with its severity and duration. Yet, the onset of serious morbidities in early adulthood among otherwise healthy adolescents with obesity is understudied. We aimed to investigate the association between adolescent BMI and serious morbidities before age 25 years. Methods In this nationwide, retrospective cohort study, we included Israeli conscripts aged 17-21 years who underwent pre-recruitment medical evaluation between Jan 1, 1996, and Dec 31, 2017, were deemed medically eligible for military service, and were recruited to the Israeli Defense Forces between 1998 and 2018. Exclusion criteria were missing height or weight or service ineligibility for non-medical or medical reasons. Baseline BMI was converted into age- specific and sex-specific percentiles and classified using the US Centers for Disease Control and Prevention categories. The primary outcome was incidence of serious morbidity disqualifying individuals from completing mandatory service. Participants were followed from enlistment until end of service (3 years for males and 2 years for females), onset of serious morbidity, or Dec 31, 2021. Cox models with adjustment to various socio-economic confounders were applied to calculate the hazard ratio (HR) and 95% CI for serious morbidity for the BMI categories. Findings A total of 1 264 355 adolescents aged 16-20 years were assessed for military service. 145 702 were excluded; 144 705 were considered ineligible for service (133 112 for non-medical reasons and 11 593 for medical reasons), and 2867 had missing height or weight data. The study included 1 118 653 individuals (622 989 [557%] males and 495 664 [443%] females), with 23 347 cases of serious morbidity recorded over 2 534 873 person-years. Incidence of serious morbidity increased across BMI groups in both sexes. Among males, compared with those with normal BMI, the adjusted HRs were 089 (95% CI 083-095) for underweight, 121 (116-127) for overweight, 139 (132-147) for obesity class 1, 282 (260-306) for obesity class 2, and 514 (437-604) for obesity class 3. For females, the respective ratios were HR 095 (95% CI 084-109) for underweight, 127 (117-137) for overweight, 163 (145-182) for obesity class 1, 400 (346-461) for obesity class 2, and 730 (565-943) for obesity class 3. Results persisted in sensitivity analyses restricted to those with unimpaired health at baseline or those in civilian-equivalent office employments. Interpretation Obesity in otherwise healthy adolescents was linked with increased risk of serious morbidity before age 25 years. Reducing adolescent obesity will have substantial short-term and long-term health benefits in young adults.

BACKGROUND:Diagnostic test evaluation requires a reference standard. We describe an approach for creating a reference standard for acute infection using unrestricted adjudication and apply it to compare biomarker tools. METHODS:Adults and children with suspected acute infection enrolled in three prospective studies at emergency departments and urgent cares were included. Adjudicators, blinded to C-reactive protein, procalcitonin, and MeMed BV (MMBV), labeled each case (bacterial/viral/non-infectious/indeterminate). Initial adjudication involved 3 adjudicators. Reference standard cohorts were defined: Microbiologically confirmed (3/3 adjudicators concur with high confidence and a concordant microbiological finding), unanimous (3/3 adjudicators concur with high confidence), suspected (3/3 adjudicators concur with high/moderate confidence or 2/3 adjudicators concur with high confidence), and all-inclusive (remaining unlabeled cases were reviewed by up to 7 additional adjudicators until reaching a leading label). RESULTS:Among 1016 patients, 156 difficult-to-diagnose cases required over 3 adjudicators. The area under the receiver operating characteristic curve in the microbiologically confirmed (n = 427), unanimous (n = 565), suspected (n = 860), and all-inclusive (n = 1016) cohorts for MMBV were 0.98 (95% confidence interval .94-1.00), 0.98 (.95-1.00), 0.95 (.92-.98) and 0.90 (.87-.93), respectively, and for procalcitonin were 0.69 (.57-.81), 0.77 (.68-.86), 0.74 (.68-.80) and 0.70 (.65-.75), respectively. A delta in performance between MMBV and procalcitonin was maintained across the different cohorts. CONCLUSIONS:Creating a reference standard that includes difficult-to-diagnose cases demands an approach to addressing diagnostic uncertainty in acute infections. Tool performance depends on the reference standard applied and decreases as the difficulty to diagnose increases, highlighting the importance of using the same reference standard when comparing tools.

AIM:To examine the added value of an elevated calculated peak right ventricular outflow tract pressure gradient as a surrogate for infective endocarditis diagnosis. METHODS:A cohort study included patients admitted between 2003 and 2020 at a tertiary children's medical centre. Patients with surgically inserted exogenous right ventricular outflow tract conduits and infective endocarditis were included. Infective endocarditis was diagnosed using the revised Duke criteria (2023). Controls had right ventricular outflow tract conduits and febrile illness from other causes. Clinical, laboratory, and echocardiographic findings, including calculated peak right ventricular outflow tract pressure gradient, were collected. RESULTS:Among 26 febrile episodes (11 with infective endocarditis, 15 controls), the infective endocarditis group had a higher peak right ventricular outflow tract pressure gradient during acute illness (70 vs. 23 mmHg, p < 0.05). On admission, 18% of infective endocarditis patients had a definite diagnosis by Duke's criteria, 45% had a probable diagnosis, and 36% lacked confirmation. Including peak right ventricular outflow tract gradient as a major criterion would yield a 90% diagnosis rate upon admission (45% definite, 45% possible). CONCLUSIONS:Increased right ventricular outflow tract pressure gradient in febrile patients with exogenous conduit in the right ventricular outflow tract is a potential marker for infective endocarditis. Including this gradient as a major Duke criterion enables earlier and more definitive diagnosis in debatable cases.

Chest radiography is a frequently used imaging modality in children. However, only fair to moderate inter-observer agreement has been reported between chest radiograph interpreters. Most studies were not performed in real-world clinical settings. Our aims were to examine the agreement between emergency department pediatricians and board-certified radiologists in a pediatric real-life setting and to identify clinical risk factors for the discrepancies. Included were children aged 3 months to 18 years who underwent chest radiography in the emergency department not during the regular hours of radiologist interpretation. Every case was reviewed by an expert panel. Inter-observer agreement between emergency department pediatricians and board-certified radiologists was assessed by Cohen’s kappa; risk factors for disagreement were analyzed. Among 1373 cases, the level of agreement between emergency department pediatricians and board-certified radiologists was “moderate” (k = 0.505). For radiographs performed after midnight, agreement was only “fair” (k = 0.391). The expert panel identified clinically relevant disagreements in 260 (18.9

AIM:Fibrinolytic therapy is commonly used in children with parapneumonic effusion, to facilitate drainage of the effusions and recovery. However, data regarding complications of this treatment in children are limited. We aimed to determine the incidence of pneumothorax (PNX) associated with intrapleural urokinase. METHODS:We analyzed retrospectively collected data of children with parapneumonic effusion who underwent chest drain insertion. The clinical course and complications, including the incidence of PNX, were compared between children who were and were not treated with urokinase. RESULTS:The study group included 120 children, of whom 57 were treated with urokinase. Children who were and were not treated with urokinase did not differ in markers of disease severity or in the length of hospitalization. Among the patients treated with urokinase compared to those not treated, the incidence of PNX was higher (35% vs. 6%, p < 0.001) and the median duration of chest drain treatment was longer (6 vs. 4 days, p < 0.001). CONCLUSION:In our pediatric cohort, intrapleural urokinase was associated with a higher incidence of PNX and did not shorten the duration of hospitalization.

OBJECTIVE:To describe for intervertebral spondylodiscitis (IS) its clinical characteristics, treatment approaches with intravenous (IV) antibiotics, and clinical implications of changes in treatment approach. STUDY DESIGN:This retrospective study included all children aged 0-18 years diagnosed with imaging-confirmed thoracic and lumbar IS from 2000 to 2022 at a tertiary pediatric hospital. Patients with longer IV treatment regimen were compared with those with a shorter clinically directed IV to oral regimen. RESULTS:In all, 124 cases were included with median age 14.9 months (IQR, 12.7-19.4 months) at diagnosis. Irritability and pain while changing diapers were common symptoms (52.4% and 49.2%, respectively). Elevated erythrocyte sedimentation rate (ESR) was the most common laboratory finding (95%; median, 50 mm/h [IQR 34-64 mm/h]). Elevated erythrocyte sedimentation rate was found in higher proportions (95%) compared with elevated C-reactive protein (76%; median, 1.8 mg/dL; P < .001). Since implementing the shorter clinically directed IV treatment duration for patients with thoracic and lumbar IS, hospitalization duration was decreased from a median of 12 to 8 days (P = .008) and IV treatment duration by a median of 14 to 8 days (P < .001). Only 1 patient (1.6%) in the clinically directed treatment group required rehospitalization owing to failure of therapy. Conversely, 9 of 124 children in the cohort suffered from IV treatment-related complications; all had been treated IV for prolonged periods. CONCLUSIONS:Early transition to oral treatment in pediatric spondylodiscitis seems to be appropriate clinically and shortens hospital stay and IV treatment duration without major negative clinical impact.

BACKGROUND:Infection with Adenovirus in children may clinically resemble a bacterial infection in several aspects, including high and prolonged fever, and increased inflammation markers. We aimed to estimate the rate of antibiotics administration among hospitalized infants with Adenovirus infection and to evaluate its justification. METHODS:Included were hospitalized patients aged 2 months - 2 years who found positive for Adenovirus in PCR tests (Ct <36). Basic epidemiological and clinical features were retrieved retrospectively. A panel of three certified pediatricians examined each case to decide whether the antibiotic treatment was justified. Subsequently, the cases were divided into two groups - the group treated with antibiotics and the untreated group. The groups were compared in terms of the various parameters. RESULTS:Out of 183 children with Adenovirus, 92 (50.3%) were treated with antibiotics. Only 42.4% of the antibiotics prescribed were medically justified. Children treated with antibiotics had a higher level of fever (39.4±0.90 vs. 38.6±0.98 °C; P<0.001), their blood oxygen saturation was higher (96.7±4.4% vs. 92.9±7.7%; P=0.0003), they were less dyspneic, and their inflammatory markers were higher as compared to those who had not been treated with antibiotics. CONCLUSIONS:Approximately half of hospitalized pediatric patients <2 years old who were found positive for Adenovirus infection were treated with antibiotics during hospitalization. Most of these treatments were found retrospectively to be unjustified. Rapid and routine Adenovirus PCR testing can potentially reduce the rate of antibiotic treatment amongst hospitalized children.

This cross-sectional study assesses the prevalence and risk of excessive sweating and joint hypermobility in Israeli adolescents aged 16 to 19 years.