Biomarkers In Children Research Articles

Differences in Cerebellar Volume as a Diagnostic and Prognostic Biomarker in Children and Adolescents With Epilepsy of Unknown Etiology.

Epilepsy is one of the most common brain diseases during childhood and adolescence. Atrophy in different brain areas is possible during epilepsy. This study aimed to verify whether cerebellar volume differences could be detected by volume analysis using magnetic resonance imaging (MRI) in children with epilepsy. In this retrospective study, 41 children (3.1-18.8 years) with epilepsy of unknown etiology were included (duration of epilepsy 1.9 ± 3 years). A cranial MRI with a volumetric 3-dimensional, T1-weighted sequence was used for volume analysis. The MRIs of 26 patients with headache (5.3-17.1 years) were analyzed for comparison. A volume analysis of the cerebellum was performed using region-based morphometry. Total cerebellar volume, total white and gray matter volume, and 48 regional lobules (L), separated into white and gray matter, were calculated. Cerebellar volumes are presented in relative ratios as the volume fraction of cerebellar volume to total intracranial volume: CV/TIV. The ratio of overall white matter volume was significantly lower in the case group (23.93 × 10-3, P = .039). A significantly lower ratio of regional white matter volume was detected in LV right (P = .031) and left (P = .014), in LVIIIB right (P = .011) and left (P = .019), and in LVIIIA left (P = .009). Our results emphasize that volume analysis of the total cerebellar volume alone is insufficient to characterize cerebellar differences in children with epilepsy. Rather, in specific cerebellar region volume analysis using region-based morphometry, children with epilepsy showed significantly lower regional volumes of lobules, which are important for sensorimotor function (LV, LVIII) and higher cognitive function (crus I).

Salivary C-reactive Protein as a Biomarker in Children with Sleep Disorders: An Evaluative Study

Salivary C-reactive Protein as a Biomarker in Children with Sleep Disorders: An Evaluative Study

EEG Biomarkers in Children and Adolescents With Feeding and Eating Disorders: Current Evidence and Future Directions.

IntroductionElectroencephalography (EEG) represents a powerful tool to detect abnormal neural dynamics in child and adolescent psychiatry. Feeding and Eating Disorders (FEDs), such as anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED), and avoidant restrictive food intake disorder (ARFID) onset in childhood and adolescence. EEG has rarely been used to examine cortical brain activity in children and adolescents with FEDs. This review aims to summarize EEG findings in FEDs amongst children and adolescents, and to highlight areas deserving further research.MethodsWe searched the literature for EEG studies on children and adolescents with FEDs using Google Scholar, PsycINFO, Medline, and PubMed.ResultsTwelve studies were identified, the majority focusing on AN (N = 10). The identified studies suggest reduced action monitoring control (preparatory waves, N200, P300), specific perceptual-cognitive styles to body/face perception (late positive potentials/early posterior negativity), as well as fundamental changes in posterior theta oscillations in AN. Behavioral traits of BN/BED (i.e., loss of control eating, emotional eating), and AN seem to be associated with an increased attentional reactivity (P300) to visual food stimuli.ConclusionElectroencephalography research in children and adolescents with FEDs is limited and mostly focused on AN. While EEG abnormalities seem consistent with a reduced top-down control and attentional allocation deficits in AN, altered attention specific to food cues emerges across FEDs. Overcoming conventional EEG analyses, and investigating spatial properties (i.e., electrical neuroimaging), will enhance our understanding of FEDs neurobiology.

Circulating miRNAs Are Associated with Inflammation Biomarkers in Children with Overweight and Obesity: Results of the I.Family Study.

Increasing data suggest that overnutrition-induced obesity may trigger an inflammatory process in adipose tissue and upturn in the innate immune system. Numerous players have been involved in governing the inflammatory response, including epigenetics. Among epigenetic players, miRNAs are emerging as crucial regulators of immune cell development, immune responses, autoimmunity, and inflammation. In this study, we aimed at identifying the involvement of candidate miRNAs in relation to inflammation-associated biomarkers in a subsample of European children with overweight and obesity participating in the I.Family study. The study sample included individuals with increased adiposity since this condition contributes to the early occurrence of chronic low-grade inflammation. We focused on the acute-phase reagent C-reactive protein (CRP) as the primary outcome and selected cytokines as plausible biomarkers of inflammation. We found that chronic low-grade CRP elevation shows a highly significant association with miR-26b-3p and hsa-miR-576-5p in boys. Furthermore, the association of CRP with hsa-miR-10b-5p and hsa-miR-31-5p is highly significant in girls. We also observed major sex-related associations of candidate miRNAs with selected cytokines. Except for IL-6, a significant association of hsa-miR-26b-3p and hsa-miR-576-5p with TNF-α, IL1-Ra, IL-8, and IL-15 levels was found exclusively in boys. The findings of this exploratory study suggest sex differences in the association of circulating miRNAs with inflammatory response biomarkers, and indicate a possible role of miRNAs among the candidate epigenetic mechanisms related to the process of low-grade inflammation in childhood obesity.

The Effect of Functional Exercise Along With Online Nutritional Education on Inflammatory Biomarkers in Children With Autism Spectrum Disorder During Covid-19 Pandemic: A Randomized Clinical Trial

Background and Objectives Autism spectrum disorder (ASD) is a neuro-developmental disorder which is mostly caused by deficits in social interactions. Lack of physical activity and poor nutritional habits are common problems in these patients which may be exaggerated by the Covid-19 pandemic. The study aims to assess the effect of functional training along with online nutrition education on inflammatory biomarkers in children with ASD. Subjects and Methods In this randomized controlled clinical trial, 80 children with ASD (age=9.73±1.29 years, weight=49.94±2.08 kg, height=146.08±40 cm, body mass index=24.71 ±1.48 kg/m2) were randomly divided into four groups of training, education, training+ education, and control. The interventions lasted for 8 weeks. The inflammatory biomarkers including white blood cell (WBC) count, C-reactive protein (CRP) level, neutrophil count, eosinophil count, and basophil count were assessed (using blood samples collected from antecubital vein) before and after the interventions. Results There was no significant difference between the groups before the interventions (P˃0.05). After the intervention, the results showed a significant decrease in WBC (P˂0.001), CRP (P=0.001), neutrophils (sig.=0.009), and eosinophil (P=0.003) in all groups. Basophil count decreased in all groups (P=0.01) except in the education group. Conclusion Functional training and online nutrition education are beneficial interventions for management of inflammatory biomarkers in children with ASD which can be used during the Covid-19 pandemic.

Investigation of Relaxin-3 Serum Levels in terms of Social Interaction, Communication, and Appetite as a Biomarker in Children with Autism.

ObjectiveTo investigate the possible relationship between relaxin-3 and autism spectrum disorder (ASD).MethodsSerum relaxin-3 was measured in 80 children (50 children diagnosed with ASD and 30 controls). Symptom severity in the ASD group was evaluated by the Childhood Autism Rating Scale (CARS). Behavioral and nutritional problems in the groups were evaluated using the Abnormal Behavior Checklist (ABC) and the Childrenʼs Eating Behavior Questionnaire (CEBQ).ResultsOur findings showed that serum relaxin-3 levels were higher in children with ASD than in the controls. The listening response sub-scale score of the CARS scale was found to decrease as the level of relaxin-3 increased. However, as relaxin-3 levels increased in children with ASD, it was found that the speech problem sub-scale score on the ABC scale and the desire to drink score on the CEBQ scale increased, but the satiety responsiveness and food fussiness scores decreased.ConclusionThis study the first to investigate serum levels of relaxin-3, which has a role in regulating social behavior and nutritional behavior in children with ASD.

Efficacy of Dupilumab in Quadrants of Elevated- vs Low- Type 2 Biomarkers in Children With Uncontrolled, Moderate-to-Severe Asthma: LIBERTY ASTHMA VOYAGE

Dupilumab, a human mAb, blocks the shared receptor component for IL-4/13, key and central drivers of type 2 inflammation. In VOYAGE (NCT02948959), dupilumab 100/200mg vs placebo every 2 weeks for 52 weeks reduced severe asthma annualized exacerbation rate (AER) and improved percent predicted pre-bronchodilator FEV1 (ppFEV1) in children aged 6-11 years with uncontrolled, moderate-to-severe asthma. We evaluated the predictive value of baseline blood eosinophil and FeNO levels as biomarkers for dupilumab response.

Assessment of Fruit and Vegetables Intake with Biomarkers in Children and Adolescents and Their Level of Validation: A Systematic Review.

Fruit and vegetables (FV) are part of a healthy diet and should be frequently consumed already at a young age. However, intake of FV is difficult to assess in children and adolescents due to various misreporting aspects. Thus, measurement of dietary biomarkers may be a promising alternative to assess FV intake more objectively at young age. To date, dietary biomarkers have been primarily studied in adults, and research focused on their usefulness in children is scarce. However, clinical studies have revealed important differences between children and adults, most importantly in their gut microbiome composition, resulting in differences in postprandial metabolism, as well as in food choices and meal compositions that may influence individual biomarker levels. Therefore, the present review aimed to identify biomarkers of FV intake (BFVI) currently available in children and adolescents and to explore whether there are any differences in the BFVI profile above between children and adolescents and adults. In addition, the current level of validation of BFVI in children and adolescents was examined. In total, 28 studies were eligible for this review, and 18 compounds were identified as potential biomarkers for FV intake in children and adolescents. Carotenoid concentration in skin was a valuable biomarker for total FV intake for both children and adult populations. Common BFVI in blood in adults (e.g., carotenoids and vitamin C) showed inconsistent results in children and adolescents. Biomarkers particularly useful in children included urinary hippuric acid as a biomarker of polyphenolic compound intake originating from FV and the combination of N-methylnicotinic acid and acetylornithine as a biomarker of bean intake. Further studies are needed to assess their kinetics, dose–response, and other validation aspects. There is limited evidence so far regarding valid BFVI in children and adolescents. Thus, to put BFVI into practice in children and adolescents, further studies, particularly based on metabolomics, are needed to identify and validate BFVI that can be used in future epidemiological studies.

Evaluation of Tubular Dysfunction Using Urine Biomarkers in Children with COVID-19

Objective: The coronavirus disease pandemic is a major problem that the world has been facing since December 2019. It mainly affects the respiratory system; however, the disease can affect the kidneys to different degrees. This study aimed to determine the changes in tubular dysfunction and inflammation parameters in children with coronavirus disease using urine biomarkers.Materials and Methods:We included 36 children who tested positive for severe acute respiratory syndrome coronavirus 2 on real-time reverse transcriptase-polymerase chain reaction using respiratory specimens. Coronavirus disease-positive and -negative period parameters were evaluated. For measurement of interleukin-1β, interleukin-6, and urine β2 microglobulin levels, patients’ urine samples were collected at diagnosis and 1 month after discharge. Additionally, routine urine and hematological parameters were evaluated concurrently.Results:For all patients, the median urine β2 microglobulin, serum urea, and lactate dehydrogenase levels were significantly higher in the coronavirus disease-positive period than in the coronavirus disease-negative period (P < .05). Further, serum platelet count was significantly lower in the coronavirus disease-positive period than in the coronavirus disease-negative period (P < .05). However, there was no difference in serum creatinine, interleukin-6, or interleukin-1β levels between the 2 periods (P > .05).Conclusion:Our results suggest kidney involvement and tubular dysfunction in patients with asymptomatic, mild, and moderate infections. Furthermore, interleukin-1β and interleukin-6 levels were high in the urine, even in non-critically ill patients. We believe that these findings contribute to the accumulation of evidence on continued inflammation in the kidney.

Prognostic Value of Cardiac Biomarkers in Children with Acute Bronchiolitis

Introduction: Determining the severity of acute bronchiolitis in children is important for the clinical management of the disease. Therefore, we aimed to reveal their prognostic importance by examining cardiac markers in our patients with acute bronchiolitis. Materials and Methods: We conducted a single-center retrospective, observational study with children with acute bronchiolitis between 1 month and 2 years of age, between December 2020 and December 2021, who were covid-19 PCR test negative and had no covid-19 contact. We scanned demographic, clinical and laboratory parameters from medical records. Results: A total of 45 (44% female) children with acute bronchiolitis, a median (IQR) age of 5 (5) months were included in the study. There were 7 (16%) mild bronchiolitis, 23 (51%) moderate and 15 (33%) severe bronchiolitis patients. The cutoff point of Nt-proBNP to be ≥1025 ng/L to predict severe bronchiolitis with a sensitivity of 71% and a specificity of 80 % at admission in children with acute bronchiolitis. Conclusion: We think that the threshold value for Nt-proBNP in the study can be used to identify patients with severe bronchiolitis in the early period and to reduce mortality and morbidity by earlier intervention.

Prognostic Value of Clinical Features and Biomarkers in Children with Sepsis and Bacterial Meningitis in the Emergency Department

Prognostic Value of Clinical Features and Biomarkers in Children with Sepsis and Bacterial Meningitis in the Emergency Department

Evaluation of Tubular Dysfunction Using Urine Biomarkers in Children with COVID-19.

The coronavirus disease pandemic is a major problem that the world has been facing since December 2019. It mainly affects the respiratory system; however, the disease can affect the kidneys to different degrees. This study aimed to determine the changes in tubular dysfunction and inflammation parameters in children with coronavirus disease using urine biomarkers. We included 36 children who tested positive for severe acute respiratory syndrome coronavirus 2 on real-time reverse transcriptase-polymerase chain reaction using respiratory specimens. Coronavirus disease-positive and -negative period parameters were evaluated. For measurement of interleukin-1β, interleukin-6, and urine β2 microglobulin levels, patients' urine samples were collected at diagnosis and 1 month after discharge. Additionally, routine urine and hematological parameters were evaluated concurrently. For all patients, the median urine β2 microglobulin, serum urea, and lactate dehydrogenase levels were significantly higher in the coronavirus disease-positive period than in the coronavirus disease-negative period (P < .05). Further, serum platelet count was significantly lower in the coronavirus disease-positive period than in the coronavirus disease-negative period (P < .05). However, there was no difference in serum creatinine, interleukin-6, or interleukin-1β levels between the 2 periods (P > .05). Our results suggest kidney involvement and tubular dysfunction in patients with asymptomatic, mild, and moderate infections. Furthermore, interleukin-1β and interleukin-6 levels were high in the urine, even in non-critically ill patients. We believe that these findings contribute to the accumulation of evidence on continued inflammation in the kidney.

Identification of phenotypes in paediatric patients with acute respiratory distress syndrome: a latent class analysis

Previous latent class analysis of adults with acute respiratory distress syndrome (ARDS) identified two phenotypes, distinguished by the degree of inflammation. We aimed to identify phenotypes in children with ARDS in whom developmental differences might be important, using a latent class analysis approach similar to that used in adults. This study was a secondary analysis of data aggregated from the Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) clinical trial and the Genetic Variation and Biomarkers in Children with Acute Lung Injury (BALI) ancillary study. We used latent class analysis, which included demographic, clinical, and plasma biomarker variables, to identify paediatric ARDS (PARDS) phenotypes within a cohort of children included in the RESTORE and BALI studies. The association of phenotypes with clinically relevant outcomes and the performance of paediatric data in adult ARDS classification algorithms were also assessed. 304 children with PARDS were included in this secondary analysis. Using latent class analysis, a two-class model was a better fit for the cohort than a one-class model (p<0·001). Latent class analysis identified two classes: class 1 (181 [60%] of 304 patients with PARDS) and class 2 (123 [40%] of 304 patients with PARDS), referred to as phenotype 1 and 2 hereafter. Phenotype 2 was characterised by higher concentrations of inflammatory biomarkers, a higher incidence of vasopressor use, and more frequent diagnosis of sepsis, consistent with the adult hyperinflammatory phenotype. All levels of severity of PARDS were observed across both phenotypes. Children with the hyperinflammatory phenotype (phenotype 2) had worse clinical outcomes than those with the hypoinflammatory phenotype (phenotype 1), with a longer duration of mechanical ventilation (median 10·0 days [IQR 6·3-21·0] for phenotype 2 vs 6·6 days [4·1-10·8] for phenotype 1, p<0·0001), and higher incidence of mortality (17 [13·8%] of 123 patients vs four [2·2%] of 181 patients, p=0·0001). When using adult phenotype classification algorithms in children, the soluble tumour necrosis factor receptor-1 (sTNFr1), vasopressor use, and interleukin (IL)-6 variables gave an area under the curve (AUC) of 0·956, and the sTNFr1, vasopressor use, and IL-8 variables gave an AUC of 0·954, compared with the gold standard of latent class analysis. Latent class analysis identified two phenotypes in children with ARDS with characteristics similar to those in adults, including worse outcomes among patients with the hyperinflammatory phenotype. PARDS phenotypes should be considered in design and analysis of future clinical trials in children. US National Institutes of Health.

Prognostic Value of Biomarkers in Children and Adolescents With Orthostatic Intolerance.

Orthostatic intolerance (OI) refers to a series of symptoms that occur during upright standing, which can be relieved when returned to the supine position. OI is a common cause of syncope in children and adolescents. In recent years, more and more studies have been carried out to assess the prognosis of OI by using biomarkers, among which, flow-mediated vasodilation, left ventricular ejection fraction and fractional shortening, hemodynamic change during head-up tilt test, detection of 24-h urinary sodium excretion, body mass index, midregional pro-adrenomedullin, and erythrocytic H2S producing rate are relatively stable, inexpensive, and easy to obtain. With the help of biomarkers, individualized treatment can be carried out to improve the long-term prognosis of children and adolescents with OI. This article reviews the prognostic value of biomarkers in children and adolescents with OI.

Comparison of Levels of Three Tobacco Smoke Exposure Biomarkers in Children of Smokers.

Objectives: Cotinine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and N-oxides are biomarkers of tobacco smoke exposure (TSE) used to assess short- and longer-term TSE. The objective of this study was to assess the associations between these TSE biomarkers, sociodemographics, parental smoking, and child TSE patterns among 0–17-year-olds. Methods: A convenience sample of 179 pediatric patients (mean (SD) age = 7.9 (4.3) years) who lived with ≥1 smoker and who had parental assessments completed and urine samples analyzed for the three TSE biomarkers of interest were included. Biomarker levels were log-transformed, univariate regression models were built and Pearson correlations were assessed. Results: In total, 100% of children had detectable levels of cotinine and >96% had detectable NNAL and N-oxide levels. The geometric means of cotinine, NNAL, and N-oxide levels were 10.1 ng/mL, 25.3 pg/mL, and 22.9 pg/mL, respectively. The mean (SD) number of daily cigarettes smoked by parents was 10.6 (6.0) cigarettes. Child age negatively correlated with urinary cotinine (r = −0.202, p = 0.007) and log NNAL levels (r = −0.275, p < 0.001). The highest log-cotinine levels were in children who were younger, of African American race, and whose parents had a lower education, an annual income ≤USD15,000, and no smoking bans. The highest log-NNAL and N-oxide levels were in children whose parents had a lower education, had no smoking bans, and were around higher numbers of cigarettes. Conclusion: Children of smokers who were younger, African American, and had no smoking bans had the highest TSE biomarker levels. Targeted interventions are needed to reduce TSE levels among high-risk children.

Imbalance of Systemic Redox Biomarkers in Children with Epilepsy: Role of Ferroptosis.

To assess if ferroptosis, a new type of programmed cell death accompanied by iron accumulation, lipid peroxidation, and glutathione depletion, occurs in children with epilepsy, and in order to identify a panel of biomarkers useful for patient stratification and innovative-targeted therapies, we measured ferroptosis biomarkers in blood from 83 unrelated children with a clinical diagnosis of epilepsy and 44 age-matched controls. We found a marked dysregulation of three ferroptosis key markers: a consistent increase of 4-hydroxy-2-nonenal (4-HNE), the main by-product of lipid peroxidation, a significant decrease of glutathione (GSH) levels, and a partial inactivation of the enzyme glutathione peroxidase 4 (GPX4), the mediator of lipid peroxides detoxification. Furthermore, we found a significant increase of NAPDH oxidase 2 (NOX2) in the blood of children, supporting this enzyme as a primary source of reactive oxygen species (ROS) in epilepsy. Additionally, since the nuclear factor erythroid 2-related factor 2 (NRF2) induction protects the brain from epileptic seizure damage, we also evaluated the NRF2 expression in the blood of children. The antioxidant and anti-inflammatory transcription factor was activated in patients, although not enough to re-establish a correct redox homeostasis for counteracting ferroptosis. Ferroptosis-mediated oxidative damage has been proposed as an emergent mechanism underlying the pathogenesis of epilepsy. Overall, our study confirms a crucial role for ferroptosis in epilepsy, leading to the identification of a panel of biomarkers useful to find new therapeutic targets. Developing innovative drugs, which act by inhibiting the ferroptosis signaling axis, may represent a promising strategy for new anti-seizure medications.

Symptom-Related Differential Neuroimaging Biomarkers in Children with Corpus Callosum Abnormalities.

We aimed to identify symptom-related neuroimaging biomarkers for patients with dysgenesis of the corpus callosum (dCC) by summarizing neurological symptoms reported in clinical evaluations and correlating them with retrospectively collected structural/diffusion brain magnetic resonance imaging (MRI) measures from 39 patients/controls (mean age 8.08 ± 3.98). Most symptoms/disorders studied were associated with CC abnormalities. Total brain (TB) volume was related to language, cognition, muscle tone, and metabolic/endocrine abnormalities. Although white matter (WM) volume was not related to symptoms studied, gray matter (GM) volume was related to cognitive, behavioral, and metabolic/endocrine disorders. Right hemisphere (RH) cortical thickness (CT) was linked to language abnormalities, while left hemisphere (LH) CT was linked to epilepsy. While RH gyrification index (GI) was not related to any symptoms studied, LH GI was uniquely related to cognitive disorders. Between patients and controls, GM volume and LH/RH CT were significantly greater in dCC patients, while WM volume and LH/RH GI were significantly greater in controls. TB volume and diffusion indices for tissue microstructures did not show differences between the groups. In summary, our brain MRI-based measures successfully revealed differential links to many symptoms. Specifically, LH GI abnormality can be a predictor for dCC patients, which is uniquely associated with the patients' symptom. In addition, patients with CC abnormalities had normal TB volume and overall tissue microstructures, with potentially deteriorated mechanisms to expand/fold the brain, indicated by GI.

Inflammatory Biomarkers Are Associated With a Decline in Functional Status at Discharge in Children With Acute Respiratory Failure: An Exploratory Analysis.

Secondary analysis of the Genetic Variation and Biomarkers in Children with Acute Lung Injury (R01HL095410) study. Twenty-two PICUs participating in the multisite clinical trial, Randomized Evaluation of Sedation Titration for Respiratory Failure (U01 HL086622) and the ancillary study (Biomarkers in Children with Acute Lung Injury). Children 2 weeks to 17 years requiring invasive mechanical ventilation for acute airways and/or parenchymal lung disease. Patients with an admission Pediatric Overall Performance Category greater than 3 (severe disability, coma, or brain death) were excluded. None. Among survivors, 387 patients had no worsening of Pediatric Overall Performance Category at discharge while 40 had worsening functional status, defined as any increase in Pediatric Overall Performance Category from baseline. There was no significant relationship between worsening of Pediatric Overall Performance Category and interleukin-8 or plasminogen activator inhibitor-1 on any day. There was no significant relationship between interleukin-1 receptor antagonist, or thrombomodulin, and worsening Pediatric Overall Performance Category on day 1. Plasma interleukin-1 receptor antagonist and thrombomodulin were significantly elevated on days 2 and 3 in those with worse functional status at discharge compared with those without. In multivariable analysis, interleukin-1 receptor antagonist and thrombomodulin were associated with a decline in functional status on days 2 and 3 after adjustment for age and highest oxygenation index. However, after adjusting for age and cardiovascular failure, only day 2 thrombomodulin levels were associated with a worsening in Pediatric Overall Performance Category. Higher levels of interleukin-1 receptor antagonist or thrombomodulin following intubation were associated with worse Pediatric Overall Performance Category scores at hospital discharge in children who survive acute respiratory failure. These data suggest that persistent inflammation may be related to functional decline.

Tumor Necrosis Factor-Like Weak Inducer of Apoptosis and Selected Cytokines—Potential Biomarkers in Children with Solitary Functioning Kidney

This study was performed to explore serum tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its dependent cytokines urinary excretion: monocyte chemoattractant protein-1 (MCP-1) and regulated on activation, normal T cell expressed and secreted chemokine (RANTES) with their relation to the kidney function parameters in children with solitary functioning kidney (SFK). The study included 80 children and adolescents (median age 9.75 year) with congenital and acquired (after surgical removal) SFK. Serum TWEAK and urinary MCP-1 and RANTES levels were significantly higher in SFK patients (p < 0.05). The serum TWEAK was positively related to serum creatinine (r = 0.356; p < 0.001). Moreover, in SFK the receiver operating characteristic analyses revealed good diagnostic profile for serum TWEAK with AUC (Area Under The Curve)—0.853, uRANTES—0.757, and for RANTES/cr.: AUC—0.816. Analysis carried out to identify children with impaired renal function (albuminuria and/or decreased estimated glomerular filtration rate < 90 mL/min/1.73 m2 and/or hypertension) showed good profile for TWEAK (AUC—0.79) and quite good profile for uRANTES and RANTES/cr. (AUC 0.66 and 0.631, respectively). This is the first study investigating serum TWEAK and urinary excretion of MCP-1 and RANTES together in children with SFK. Obtained results indicate that TWEAK and RANTES may serve as potential markers of renal impairment.

Diagnostic Value of Monocyte-to-Lymphocyte Ratio Against Other Biomarkers in Children With Appendicitis.

This study aimed to investigate diagnostic value of monocyte-to-lymphocyte ratio as a novel biomarker in children with appendicitis and to compare with other biomarkers. A total of 683 children were included in this retrospective study. Patients were categorized as acute appendicitis (AA, n = 254), perforated appendicitis (PA, n = 82), nonspecific abdominal pain (NAP, n = 197), and control (n = 150). The groups were compared for demographics, duration of symptoms, monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), white blood cell count, neutrophil percentage (NP), C-reactive protein (CRP), mean platelet volume, and sodium level. There was a significant difference between all groups for MLR, PLR, and CRP. White blood cell count, NP, and NLR were significantly increased in patients with appendicitis, but there was no significant difference in the differential diagnosis between PA and AA. Sodium levels significantly decreased in patients with appendicitis. No statistically significance was determined between all groups in term of mean platelet volume. Among the biomarkers, MLR showed the highest diagnostic value (area under the receiver operator characteristic curve = 0.798) for AA, while CRP showed excellent diagnostic value (area under the receiver operator characteristic curve = 0.897) for PA. To our knowledge, this is the first study showing that MLR is a valuable parameter to differentiate patients with and without appendicitis. White blood cell, NP, and NLR are also useful parameters. On the other hand, an increased CRP level and hyponatremia are indicators of PA.