Shock index and shock index, pediatric age-adjusted as predictors of mortality in pediatric patients with trauma: A systematic review and meta-analysis.

This study aimed to assess the predictive ability of the shock index (SI) and the shock index, pediatric age-adjusted (SIPA) for mortality among pediatric patients with trauma (aged ≤ 18 years). A systematic search used PubMed, Embase, and Cochrane Library databases to identify pertinent articles published from their inception to 13 February 2023. For each SI and SIPA, the pooled sensitivity, specificity, diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic curve (AUC) with the corresponding 95% confidence intervals were calculated. We planned a priori meta-regression analyses to explore heterogeneity using the following covariates: country, clinical setting, type of center, data source, and cutoff value. Twelve studies were included based on the inclusion criteria. Among them, nine studies with 195,469 patients were included for the SIPA at the hospital, four studies with 4,970 patients were included for the pre-hospital SIPA, and seven studies with 606,445 patients were included to assess the ability of the SI in predicting mortality. The pooled sensitivity and specificity with 95% confidence interval for predicting mortality were as follows: 0.58 (0.44-0.70) and 0.72 (0.60-0.82), respectively, for the SIPA at the hospital; 0.61 (0.47-0.74) and 0.67 (0.61-0.73), respectively, for the pre-hospital SIPA; and 0.71 (0.59-0.81) and 0.45 (0.31-0.59), respectively for the SI. The DOR were 3.80, 3.28, and 2.06 for the SIPA at the hospital, pre-hospital SIPA, and SI, respectively. The AUC were 0.693, 0.689, and 0.618 for the SIPA at the hospital, pre-hospital SIPA, and SI, respectively. The SI and SIPA are simple predictive tools with sufficient accuracy that can be readily applied to pediatric patients with trauma, but SIPA and SI should be utilized cautiously due to their limited sensitivity and specificity, respectively.

Mortality after cardiac arrest in children less than 2 years: relevant factors.

BACKGROUND: There are only scant studies of predicting outcomes of pediatric resuscitation due to lack of population-based data. This study aimed to determine variable factors that may impact the survival of resuscitated children aged under 24 months. METHODS: This is a retrospective study of 66 children under 24 months. Cardiopulmonary resuscitation (CPR) with pediatric advanced life support guideline was performed uniformly for all children. Linear regression analysis with variable factors was conducted to determine impacts on mortality. RESULT: Factors with statistically significant increases in mortality were the number of administered epinephrine (p value < 0.001), total CPR duration (p value < 0.001), in-hospital CPR duration of out-hospital cardiac arrest (p value < 0.001), and changes in cardiac rhythm (p value < 0.040). However, there is no statistically significant association between patient outcomes and remaining factors such as age, sex, underlying disease, etiology, time between last normal to CPR, initial CPR location, initial cardiac rhythm, venous access time, or inotropic usage. CONCLUSION: More than 10 times of epinephrine administration and CPR duration longer than 30 minutes were associated with a higher mortality rate, while each epinephrine administration and prolonged CPR time increased mortality. IMPACT STATEMENT: This study analyzed various factors influencing mortality after cardiac arrest in patients under 24 months. Increased number of administered epinephrine and prolonged cardiopulmonary resuscitation duration do not increase survival rate in patients under 24 months. In patients with electrocardiogram rhythm changes during CPR, mortality increased when the rhythm changed into asystole in comparison to no changes occurring in the rhythm.

Optimal Use and Need for Therapeutic Drug Monitoring of Teicoplanin in Children: A Systematic Review.

BACKGROUND: Teicoplanin is a glycopeptide antimicrobial that treats serious invasive infections caused by gram-positive bacteria, such as the methicillin-resistant Staphylococcus aureus. Despite some comparable advantages, there is no guideline or clinical recommendation for teicoplanin in the pediatric population, unlike vancomycin where abundant studies and the recently revised guideline on therapeutic drug level monitoring (TDM) exist. METHODS: The systematic review was performed in accordance with the preferred reporting items for systematic reviews. Two authors (JSC and SHY) searched PubMed, Embase, and Cochrane Library databases using relevant terms independently. RESULTS: Fourteen studies were finally included with a total of 1,380 patients. TDM was available in 2,739 samples collected in the nine studies. Dosing regimens varied widely, and eight studies used recommended dosing regimens. Timing for measuring TDM was mostly 72-96 hours or longer after the initiation of the first dose, which was expected to be a steady-state. The majority of studies had target trough levels of 10 µg/mL or above. Three studies reported that the clinical efficacy and treatment success rate of teicoplanin was 71.4%, 87.5%, and 88%. Adverse events associated with teicoplanin use were described in six studies with a focus on renal and/or hepatic impairment. Except for one study, no significant relation was noted between the incidence of adverse events and trough concentration. CONCLUSION: Current evidence on teicoplanin trough levels in pediatric populations is insufficient due to heterogeneity. However, target trough levels with favorable clinical efficacy are achievable by recommended dosing regimen in the majority of patients.

Delayed Influenza Treatment in Children With False-Negative Rapid Antigen Test: A Retrospective Single-Center Study in Korea 2016-2019.

BACKGROUND: We aimed to examine the delay in antiviral initiation in rapid antigen test (RAT) false-negative children with influenza virus infection and to explore the clinical outcomes. We additionally conducted a medical cost-benefit analysis. METHODS: This single-center, retrospective study included children (aged < 10 years) with influenza-like illness (ILI), hospitalized after presenting to the emergency department during three influenza seasons (2016-2019). RAT-false-negativity was defined as RAT-negative and polymerase chain reaction-positive cases. The turnaround time to antiviral treatment (TAT) was from the time when RAT was prescribed to the time when the antiviral was administered. The medical cost analysis by scenarios was also performed. RESULTS: A total of 1,430 patients were included, 7.5% were RAT-positive (n = 107) and 2.4% were RAT-false-negative (n = 20). The median TAT of RAT-false-negative patients was 52.8 hours, significantly longer than that of 4 hours in RAT-positive patients (19.2-100.1, P < 0.001). In the multivariable analysis, TAT of ≥ 24 hours was associated with a risk of severe influenza infection and the need for mechanical ventilation (odds ratio [OR], 6.8, P = 0.009 and OR, 16.2, P = 0.033, respectively). The medical cost varied from $11.7-187.3/ILI patient. CONCLUSION: Antiviral initiation was delayed in RAT-false-negative patients. Our findings support the guideline that children with influenza, suspected of having severe or progressive infection, should be treated immediately.

Age-adjusted quick Sequential Organ Failure Assessment score for predicting mortality and disease severity in children with infection: a systematic review and meta-analysis.

We assessed the diagnostic accuracy of the age-adjusted quick Sequential Organ Failure Assessment score (qSOFA) for predicting mortality and disease severity in pediatric patients with suspected or confirmed infection. We conducted a systematic search of PubMed, EMBASE, the Cochrane Library, and Web of Science. Eleven studies with a total of 172,569 patients were included in the meta-analysis. The pooled sensitivity, specificity, and diagnostic odds ratio of the age-adjusted qSOFA for predicting mortality and disease severity were 0.69 (95% confidence interval [CI] 0.53-0.81), 0.71 (95% CI 0.36-0.91), and 6.57 (95% CI 4.46-9.67), respectively. The area under the summary receiver-operating characteristic curve was 0.733. The pooled sensitivity and specificity for predicting mortality were 0.73 (95% CI 0.66-0.79) and 0.63 (95% CI 0.21-0.92), respectively. The pooled sensitivity and specificity for predicting disease severity were 0.73 (95% CI 0.21-0.97) and 0.72 (95% CI 0.11-0.98), respectively. The performance of the age-adjusted qSOFA for predicting mortality and disease severity was better in emergency department patients than in intensive care unit patients. The age-adjusted qSOFA has moderate predictive power and can help in rapidly identifying at-risk children, but its utility may be limited by its insufficient sensitivity.

Paediatric Trauma Score as a non-imaging tool for predicting intracranial haemorrhage in patients with traumatic brain injury.

To identify a useful non-imaging tool to screen paediatric patients with traumatic brain injury for intracranial haemorrhage (ICH). We retrospectively analysed patients aged < 15 years who visited the emergency department with head trauma between January 2015 and September 2020. We divided patients into two groups (ICH and non-ICH) and compared their demographic and clinical factors. Among 85 patients, 21 and 64 were in the ICH and non-ICH groups, respectively. Age (p = 0.002), Pediatric trauma score (PTS; p < 0.001), seizure (p = 0.042), and fracture (p < 0.001) differed significantly between the two groups. Factors differing significantly between the groups were as follows: age (odds ratio, 0.84, p = 0.004), seizure (4.83, p = 0.013), PTS (0.15, p < 0.001), and fracture (69.3, p < 0.001). Factors with meaningful cut-off values were age (cut-off [sensitivity, specificity], 6.5 [0.688, 0.714], p = 0.003) and PTS [10.5 (0.906, 0.81), p < 0.001]. Based on the previously known value for critical injury (≤ 8 points) and the cut-off value of the PTS identified in this study (≤ 10 points), we divided patients into low-risk, medium-risk, and high-risk groups; their probabilities of ICH (95% confidence intervals) were 0.16-12.74%, 35.86-89.14%, and 100%, respectively. PTS was the only factor that differed significantly between mild and severe ICH cases (p = 0.012). PTS is a useful screening tool with a high predictability for ICH and can help reduce radiation exposure when used to screen patient groups before performing imaging studies.

Diagnostic Accuracy of Immunochromatographic Tests for the Detection of Norovirus in Stool Specimens: a Systematic Review and Meta-Analysis.

Noroviruses are the leading cause of acute gastroenteritis in all age groups and constitute a major health and economic burden worldwide. This systematic review and meta-analysis aimed to determine the diagnostic accuracy of immunochromatographic tests (ICTs) for the detection of norovirus in stool specimens, which has not been performed previously. In this systematic review and meta-analysis (registered on PROSPERO, CRD42020186911), we searched Medline/PubMed, Embase, Cochrane Library, and Web of Science for all studies published up to 16 May 2020. The values for sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), and diagnostic odds ratio (DOR) of ICTs with 95% confidence interval (CI) were pooled using a bivariate random-effects model. The summary receiver operating characteristic curve and area under the curve were used to summarize overall test accuracy. We included 43 studies describing 7,428 samples. The overall estimates of sensitivity, specificity, LR+, LR-, DOR, and accuracy of ICT for diagnosing norovirus were 0.61 (95% CI, 0.54 to 0.67), 0.97 (95% CI, 0.95 to 0.98), 17.08 (95% CI, 11.15 to 26.18), 0.40 (95% CI, 0.34 to 0.46), 53.9 (95% CI, 31.32 to 92.78), and 0.928, respectively. Significant differences in pooled sensitivities were noted between age groups and in pooled DOR and LR+ between genogroups of included samples. ICT provides low sensitivity but high specificity and accuracy for detecting norovirus. Thus, an ICT for norovirus can be a rapid and convenient way for identifying patients early; however, a negative result cannot rule out norovirus infection and should be confirmed by a reference test.

Blood Procalcitonin Level as a Diagnostic Marker of Pediatric Bacterial Meningitis: A Systematic Review and Meta-Analysis.

Early diagnosis and treatment of bacterial meningitis in children are essential, due to the high mortality and morbidity rates. However, lumbar puncture is often difficult, and cerebrospinal fluid (CSF) culture takes time. This meta-analysis aims to determine the diagnostic accuracy of blood procalcitonin for detecting bacterial meningitis in children. We conducted a systematic search on electronic databases to identify relevant studies. Pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated, and a hierarchical summary receiver operating characteristic curve and area under the curve (AUC) were determined. Eighteen studies with 1462 children were included in the analysis. The pooled sensitivity, specificity, and the DOR of blood procalcitonin for detecting bacterial meningitis were 0.87 (95% confidence interval (CI): 0.78-0.93); 0.85 (95% CI: 0.75-0.91), and 35.85 (95% CI: 10.68-120.28), respectively. The AUC for blood procalcitonin was 0.921. Blood procalcitonin also showed higher diagnostic accuracy for detecting bacterial meningitis than other conventional biomarkers, including serum C-reactive protein and leukocyte count, CSF leukocyte and neutrophil count, and CSF protein and glucose levels. Blood procalcitonin can be a good supplemental biomarker with high diagnostic accuracy in detecting bacterial meningitis in children.

Predictive factors for bacteremia in febrile infants with urinary tract infection.

This study aimed to investigate the predictive factors of concomitant bacteremia occurring in febrile infants who initially presented with pyuria and fever, and were subsequently diagnosed with culture-proven urinary tract infection (UTI). We conducted a retrospective cohort study for January 2010-October 2018 that included infants younger than six months with febrile UTI at a tertiary hospital. The study included 463 patients, of whom 34 had a concomitant bacteremic UTI. Compared to those in the non-bacteremic urinary tract infection (UTI) group, the bacteremic UTI group had a lower mean age; higher levels of C-reactive protein (CRP), delta neutrophil index (DNI, reflects the fraction of immature granulocytes) and blood urea nitrogen (BUN); lower levels of hemoglobin (Hb) and albumin; and a lower platelet count. Vesicoureteral reflux (VUR) was detected nearly twice as often in patients with bacteremic UTI compared to those with non-bacteremic UTI (59.3% vs. 30.6%; P = 0.003). Univariate logistic analyses showed that age ≤90 days; higher DNI, CRP, and creatinine levels; lower Hb and albumin levels; and the presence of VUR were predictors for bacteremic UTI. On multivariate logistic regression analysis, age ≤90 days, higher DNI and CRP levels, and the presence of VUR were independent predictors of bacteremic UTI. The area under the receiver operating characteristic curve of the multivariate model was 0.859 (95% CI, 0.779-0.939; P < 0.001). Age ≤90 days, higher DNI and CRP values may help predict bacteremia of febrile infants younger than 6 months with UTI. Vesicoureteral reflux imaging is also recommended in infants with bacteremic UTI to evaluate VUR.

Immunochromatography for the diagnosis of Mycoplasma pneumoniae infection: A systematic review and meta-analysis.

The aim of this study was to evaluate the diagnostic performance of immunochromatographic tests (ICTs) for the detection of Mycoplasma pneumoniae. Medline/Pubmed, Embase, the Cochrane Library, and ISI Web of Science were searched through June 12, 2019 for relevant studies that used ICTs for the detection of M. pneumoniae infection with polymerase chain reaction (PCR) or microbial culturing as reference standards. Pooled diagnostic accuracy with 95% confidence interval (CI) was calculated using a bivariate random effects model. We also constructed summary receiver operating characteristic curves and calculated the area under the curve (AUC). Statistical heterogeneity was evaluated by χ2 test or Cochrane's Q test. Thirteen studies including 2,235 samples were included in the meta-analysis. The pooled sensitivity and specificity for diagnosing M. pneumoniae infection were 0.70 (95% CI: 0.59-0.79) and 0.92 (95% CI: 0.87-0.95), respectively. The positive likelihood ratio (LR) was 8.94 (95% CI: 4.90-14.80), negative LR 0.33 (95% CI: 0.22-0.46), diagnostic odds ratio 29.20 (95% CI: 10.70-64.20), and AUC 0.904. In subgroup analysis, ICTs demonstrated similar pooled sensitivities and specificities in populations of children only and mixed populations (children + adults). Specimens obtained from oropharyngeal swabs exhibited a higher sensitivity and specificity than those of nasopharyngeal swab. Moreover, pooled estimates of sensitivity and accuracy for studies using PCR as a reference standard were higher than those using culture. The pooled sensitivity and specificity of Ribotest Mycoplasma®, the commercial kit most commonly used in the included studies, were 0.66 and 0.89, respectively. Overall, ICT is a rapid user-friendly method for diagnosing M. pneumoniae infection with moderate sensitivity, high specificity, and high accuracy. This suggests that ICT may be useful in the diagnostic workup of M. pneumoniae infection; however, additional studies are needed for evaluating the potential impact of ICT in clinical practice.

Prognostic value of the delta neutrophil index in pediatric cardiac arrest.

The delta neutrophil index (DNI), which reflects the ratio of circulating immature neutrophils, has been reported to be highly predictive of mortality in systemic inflammation. We investigated the prognostic significance of DNI value for early mortality and neurologic outcomes after pediatric cardiac arrest (CA). We retrospectively analyzed the data of eligible patients (<19 years in age). Among 85 patients, 55 subjects (64.7%) survived and 36 (42.4%) showed good outcomes at 30 days after CA. Cox regression analysis revealed that the DNI values immediately after the return of spontaneous circulation, at 24 hours and 48 hours after CA, were related to an increased risk for death within 30 days after CA (P < 0.001). A DNI value of higher than 3.3% at 24 hours could significantly predict both 30-day mortality (hazard ratio: 11.8; P < 0.001) and neurologic outcomes (odds ratio: 8.04; P = 0.003). The C statistic for multivariable prediction models for 30-day mortality (incorporating DNI at 24 hours, compression time, and serum sodium level) was 0.799, and the area under the receiver operating characteristic curve of DNI at 24 hours for poor neurologic outcome was 0.871. Higher DNI was independently associated with 30-day mortality and poor neurologic outcomes after pediatric CA.

Mesenteric venous thrombosis as a complication of appendicitis in an adolescent: A case report and literature review.

RATIONALE: Mesenteric venous thrombosis is an uncommon but potentially fatal condition that can cause bowel ischemia. It results from a systemic hypercoagulable state or abdominal infection draining into the portal venous system. Several cases regarding portomesenteric venous thrombosis as a complication of appendicitis were reported in adults, but there are far fewer reports in pediatric patients. The mortality rate of the condition is high if untreated, especially in children, reaching up to 50%. PATIENT CONCERNS: A healthy 15-year-old male with no significant past medical history presented with right lower quadrant pain, lethargy, and fever. The computed tomography scan showed a focal thrombosis at the superior mesenteric vein branch and an inflamed appendix. DIAGNOSES: Mesenteric venous thrombosis complicating acute appendicitis. INTERVENTIONS: Intravenous antibiotics along with anticoagulants and laparoscopic appendectomy OUTCOMES:: After 1 month, a follow-up ultrasonography revealed full resolution of the thrombosis. LESSONS: Appendicitis is one of the most frequently encountered causes of pediatric surgical emergencies; therefore, physicians should be conscious of mesenteric venous thrombosis as a possible complication of acute appendicitis, irrespective of whether patients have thrombophilic conditions or not.

Presepsin as a diagnostic marker of sepsis in children and adolescents: a systemic review and meta-analysis.

BACKGROUND: Early diagnosis of sepsis in pediatric patients is vital but remains a major challenge. Previous studies showed that presepsin is potentially a reliable diagnostic biomarker for sepsis in adult and neonates. However, there is no pooled analysis of its efficacy as a diagnostic biomarker for sepsis in children. The aims of the present meta-analysis were to assess the overall diagnostic accuracy of presepsin in pediatric sepsis and compare it to those for C-reactive protein (CRP) and procalcitonin (PCT). METHODS: A systematic literature search was performed in Medline/Pubmed, Embase, the Cochrane Library, and ISI Web of Science to identify relevant studies reporting the diagnostic accuracy of presepsin in patients with pediatric sepsis. Sensitivities and specificities were pooled by bivariate meta-analysis. Heterogeneity was evaluated by χ2 test. RESULTS: We identified 129 studies in total. Most were disqualified on the basis of their titles/abstracts and duplication. Four studies were included in the final analysis. They comprised 308 patients aged between 1 mo and 18 y. The pooled diagnostic sensitivity and specificity of presepsin were 0.94 (95% confidence interval [CI]: 0.74-0.99) and 0.71 (95% CI: 0.35-0.92), respectively. The pooled diagnostic odds ratio, positive likelihood ratio (LR), and negative LR of presepsin were 32.87 (95% CI: 2.12-510.09), 3.24 (95% CI, 1.14-12.38), and 0.08 (95% CI, 0.01-0.74), respectively. Heterogeneity was found in both sensitivity (χ2 = 11.17; P = 0.011) and specificity (χ2 = 65.78; P < 0.001). No threshold effect was identified among the studies (r = - 0.938). The pooled sensitivity of presepsin (0.94) was higher than that of CRP (0.51) and PCT (0.76), whereas the overall specificity of presepsin (0.71) was lower than that of CRP (0.81) and PCT (0.76). The AUC of presepsin (0.925) was higher than that of CRP (0.715) and PCT (0.820). CONCLUSION: Currently available evidence indicates that presepsin has higher sensitivity and diagnostic accuracy, but lower specificity, than PCT or CRP in detecting sepsis in children. However, these results must be carefully interpreted as the number of studies included was small and the studies were statistically heterogeneous.

Early features of Kawasaki disease with pyuria in febrile infants younger than 6 months.

BACKGROUND: Children with Kawasaki disease (KD) and pyuria have been misdiagnosed with urinary tract infection (UTI). We compared clinical and laboratory features at admission between two groups of infants under 6 months of age who showed initial pyuria, to identify the initial clues suggestive of KD. METHODS: We retrospectively reviewed the medical records of children with fever who were under 6 months of age with pyuria, over a 10-year period (2007-2017). We included infants with sterile pyuria who were finally diagnosed with KD and those with UTI. RESULTS: During the period investigated, 12 (9.9%) KD patients with sterile pyuria and 378 infants with UTI were included in this study. Older age (P < 0.01), a longer duration of fever; total and before admission (P < 0.01), more negative nitrite test (P < 0.01), higher platelet count (P = 0.04), increased C-reactive protein (CRP) (P < 0.01) and erythrocyte sedimentation rate (ESR) (P < 0.01), were identified as initial features of infants finally diagnosed with KD. In the receiver operating characteristic analysis, optimal cut-off values of 509 k/µL for platelet count, 60 mg/L for CRP, and 68 mm/H for ESR were selected. Patients with ESR > 68 mm/hr had a ninefold higher odds of KD compared to those with lower ESR levels (odds ratio: 8.963, 95% confidence intervals: 1.936-41.493, P = 0.005), whereas CRP and platelet count could not significantly increase in the odds of KD at a cut-off point. CONCLUSION: Persistent fever, elevated ESR, and negative urine nitrite test can serve as early clues to suspect KD in febrile infants with pyuria.

Association of extended nitric oxide parameters with bronchial hyperresponsiveness and bronchodilator response in children with asthma.

Theoretical non-linear modeling of exhaled nitric oxide has revealed extended flow-independent parameters that could explain where or how nitric oxide is produced in the lung and transferred to the airway gas stream. We aimed to evaluate the associations of bronchial hyperresponsiveness and bronchodilator response with extended flow-independent nitric oxide parameters. Nitric oxide (30, 50, 100, 200 ml s-1) was measured in 432 children with asthma on the same day with either a methacholine challenge test (n = 156) or spirometry with bronchodilator (n = 276; 96 previously diagnosed with asthma and treated with inhaled corticosteroid, 37 with acute exacerbation treated with systemic corticosteroid). We additionally included 107 healthy controls for evaluation of the suitability of the non-linear model of exhaled nitric oxide. In asthmatic children, the response-dose ratio of the methacholine challenge test was correlated positively with bronchial nitric oxide (JawNO) and airway tissue nitric oxide (CawNO) (r = 0.367 and r = 0.299, respectively; both p < 0.001), while the change in forced expiratory volume in 1 s, representing bronchodilator response, was associated positively with only JawNO (r = 0. 216, p < 0.001). On multiple regression, JawNO, CawNO, and the diffusing capacity of NO (DawNO) were significantly associated with the response-dose ratio. JawNO was significantly associated with change in forced expiratory volume in children with stable asthma but not those with acute exacerbation. Our findings suggest that bronchial hyperresponsiveness is associated with CawNO while factors other than airway tissue inflammation could affect bronchodilator response in children with mild asthma. Systemic corticosteroid use during asthma exacerbation could affect the association of bronchodilator response with extended nitric oxide parameters.

Airway hyperresponsiveness to mannitol and methacholine and exhaled nitric oxide in children with asthma.

OBJECTIVE: Asthma is characterized by airway hyperresponsiveness (AHR), inflammation, and obstruction. AHR to stimuli that indirectly cause bronchial smooth muscle (BSM) contractions via release of endogenous mediators is thought to better reflect airway inflammation than AHR to stimuli that act directly on BSM. Fractional exhaled nitric oxide (FeNO) is a useful parameter for noninvasive clinical airway inflammation assessments. Accordingly, this study aimed to examine the relationships of mannitol and methacholine challenge test outcomes with FeNO and the influence of inhaled corticosteroid treatment in children with asthma. METHODS: One hundred thirty-four asthmatic children (89 males; ages: 5-17 years, median: 9 years) underwent spirometry, FeNO measurement, serum total/specific IgE testing, and blood eosinophil count. All subjects were challenged with mannitol dry powder (MDP; AridolH, Pharmaxis, Australia) and methacholine at 7-day intervals. Data of steroid-treated and steroid-naïve children were compared. RESULTS: Positive responses to MDP and methacholine challenge tests were observed in 74.6% and 67.2% of total subject group, respectively, and 72 children had positive response to both challenge tests. The median FeNO level, response-dose ratio (RDR) of PC20 methacholine, and RDR of PD15 MDP were significantly higher in the steroid-treated group than in the steroid-naïve group (p < 0.001, 0.226, and 0.004, respectively). FeNO levels associated significantly with PD15 MDP and RDR PD15 MDP in total subject populations (p = 0.016 and 0.003, respectively); however, a significant correlation between FeNO and RDR PD15 MDP was observed only in the steroid-naïve group. CONCLUSIONS: Compared with AHR to methacholine, AHR to MDP more closely reflected the level of FeNO in steroid-naïve asthmatic children.

Serum clusterin level in children with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease. Clusterin is a sensitive cellular biosensor of oxidative stress and has been studied as a marker to assess inflammatory diseases. The clusterin levels in AD have not been evaluated thus far. OBJECTIVE: We evaluated serum clusterin levels in children with AD and assessed the relationship between serum clusterin levels and the severity of AD. METHOD: The study enrolled a total 140 children, of whom 100 had AD (n = 100) and 40 were healthy (n = 40). The severity of AD was scored by using the SCORing Atopic Dermatitis (SCORAD). Total serum immunoglobulin E and specific immunoglobulin E levels against egg whites, cow's milk, peanuts, soybeans, wheat, and Dermatophagoides farinae were measured. Clusterin levels in serum were measured by enzyme-linked immunosorbent assay. RESULTS: The mean (interquartile range) age of the children was 5.1 years (1.3-8.4 years), and 92 (69.3%) of the children were boys. The mean (standard deviation) SCORAD index was 50.4 ± 17. The mean (standard deviation) clusterin level of children with AD was higher than that in the healthy control group children (148.13 ± 4.3 pg/mL versus 144.85 ± 5.1 pg/mL; p = 0.001). Serum clusterin levels were correlated with the SCORAD index (r = 0.327, p = 0.002). CONCLUSIONS: The serum clusterin level was higher in children with AD than in the healthy control group and increased with the severity of AD. Serum clusterin may be a candidate molecule that reflects AD and its severity.

Vitamin D levels in allergic rhinitis: a systematic review and meta-analysis.

BACKGROUND: We aimed to systematically review observational studies investigating the relationship between vitamin D levels and allergic rhinitis (AR). METHODS: Studies were selected if they evaluated the relationship between vitamin D levels and AR, and included studies that evaluated other allergic conditions if those studies also contained data on AR. We assessed the incidence and prevalence of AR according to vitamin D levels and compared vitamin D levels in patients with AR to levels in controls. RESULTS: Nineteen studies were selected. Of these, only seven focused solely on AR; 10 studies evaluated the other allergic diseases as well as AR; and two studies evaluated asthma primarily, but also included data on patients with AR. The pooled odds ratios (ORs) for the incidence of AR according to vitamin D levels were not statistically significant for either children or adults. Lower vitamin D levels were associated with a higher AR prevalence only in children (pooled OR [95% confidence interval (CI)], 0.75 [0.58, 0.98]). The pooled mean vitamin D level in patients with AR was lower than that of controls only in children (pooled means difference [95% CI], -7.63 [-13.08, -2.18]). CONCLUSIONS: Prior vitamin D levels were not related to developing AR, but lower vitamin D levels were associated with a higher AR prevalence only in children. There is insufficient evidence to support vitamin D supplementation for AR prevention. However, physicians should consider evaluating patients for vitamin D deficiency during AR management, especially in children.

High-Sensitivity C-Reactive Protein Can Reflect Small Airway Obstruction in Childhood Asthma.

PURPOSE: High-sensitivity assays enabled the identification of C-reactive protein (hs-CRP) at levels that were previously undetectable. We aimed to determine if hs-CRP could reflect airway inflammation in children, by comparing hs-CRP with spirometry and impulse oscillometry (IOS) parameters and symptomatic severities. MATERIALS AND METHODS: A total of 276 asthmatic children who visited Severance Children's Hospital from 2012-2014 were enrolled. Serum hs-CRP and pulmonary function tests were performed on the same day. Patients were divided into hs-CRP positive and negative groups (cut-off value, 3.0 mg/L). RESULTS: Of the 276 asthmatic children [median age 7.5 (5.9/10.1) years, 171 boys (62%)], 39 were hs-CRP positive and 237 were negative. Regarding spirometry parameters, we observed significant differences in maximum mid-expiratory flow, % predicted (FEF25₋75) (p=0.010) between hs-CRP positive and negative groups, and a negative correlation between FEF25₋75 and hs-CRP. There were significant differences in the reactance area (AX) (p=0.046), difference between resistance at 5 Hz and 20 Hz (R5-R20) (p=0.027), resistance at 5 Hz, % predicted (R5) (p=0.027), and reactance at 5 Hz, % predicted (X5) (p=0.041) between hs-CRP positive and negative groups. There were significant positive correlations between hs-CRP and R5 (r=0.163, p=0.008), and X5 (r=0.164, p=0.007). Spirometry and IOS parameters had more relevance in patients with higher blood neutrophil levels in comparison to hs-CRP. CONCLUSION: Hs-CRP showed significant correlation with FEF25₋75, R5, and X5. It can reflect small airway obstruction in childhood asthma, and it is more prominent in neutrophil dominant inflammation.

Reappraisal of the Immunogenicity and Safety of Three Hepatitis A Vaccines in Adolescents.

Although the overall incidence of hepatitis A in Korea has been decreasing, adolescents remain highly vulnerable to its outbreaks. This study was conducted to compare the immunogenicity and safety of three hepatitis A vaccines in Korean adolescents. Healthy anti-hepatitis A virus seronegative subjects aged 13 to 19 yr were randomized in three equal groups to receive two doses of Avaxim™, Epaxal®, or Havrix®, 6 to 12 months apart. Seroconversion rates one month after the first dose were 98%, 95%, and 93% for Avaxim™, Epaxal®, and Havrix®, respectively. Seroconversion rates reached 100% for all vaccine groups one month after the second dose. Anti-HAV geometric mean concentrations (GMCs) were 7,207.7 mIU/mL (95% CI, 6023.1-8684.7), 1,750.5 mIU/mL (95% CI, 1362.9-2248.3), and 1,953.5 mIU/mL (95% CI, 1459.4-2614.7) after two doses of Avaxim™, Epaxal®, and Havrix® respectively. Avaxim™ was significantly more immunogenic than Epaxal® and Havrix®, whereas there were no significant differences in antibody responses between Epaxal® and Havrix®. Local and systemic solicited adverse events (AEs) were mostly of mild-to-moderate intensity and resolved within 5 days. No serious AEs were reported. In conclusion, all three vaccines are highly immunogenic and well-tolerated in Korean adolescents. (Clinical Trial Registry NCT00483470).