•Hypercytokinemia was exaggerated in AFBN patients compared with APN patients.•Serum levels of IFN-γ and IL-6 effectively distinguished AFBN from APN.•IFN-γ and IL-6 might play central roles in the ...pathophysiology of AFBN.
Acute focal bacterial nephritis (AFBN) is a severe form of upper urinary tract infection (UTI) with neurological manifestations and focal renal mass lesions on computed tomography (CT). Prolonged antibiotic therapy may improve the renal outcome, but the early differential diagnosis of AFBN from acute pyelonephritis (APN) is challenging. We searched for effective biomarkers of AFBN based on the pathophysiology of upper UTIs.
Of 52 upper UTI cases treated at Yamaguchi University between 2009 and 2016, 38 pediatric patients with AFBN (n=17) or APN (n=21) who underwent ultrasonography and/or CT were enrolled. The clinical data and serum cytokine concentrations were analyzed to differentiate AFBN from APN.
AFBN patients tended to be older, and have a higher body temperature, longer febrile period, more frequent neurological symptoms, higher immature neutrophil count, lower lymphocyte count, higher procalcitonin and urine β2-microglobulin levels. AFBN patients showed higher serum levels of IFN-γ, IL-6, IL-10 and soluble TNF-receptor 1 (sTNFR1) (all p<0.05). Although the cytokine levels were variably correlated among each other, multiple logistic regression analysis revealed that combination of IFN-γ and IL-6 levels were most relevant for distinguishing AFBN from APN. The discriminant power of the logistic equation was 0.86 in terms of the area under the curve by the ROC analysis.
Circulating 4 out of 7 cytokines in AFBN patients were at higher levels compared with those in APN patients. IFN-γ and IL-6 levels might most effectively distinguish AFBN from APN.
Abstract Backgrounds Kawasaki disease (KD) is a systemic vasculitis of childhood involving coronary arteries. Treatment for intractable cases at a higher risk of cardiac sequelae remains ...controversial. Methods Clinical outcomes of KD patients diagnosed in Yamaguchi prefecture, Japan between 2003 and 2014 were analyzed using the medical records from all 14 hospitals covering the prefecture. The study included 1487 patients (male:female, 873:614; median age at diagnosis, 24 months). Results The proportion of initial intravenous immunoglobulin (IVIG)-resistant patients increased from 7% to 23% during this decade, although no patients died. Twenty-four patients developed coronary artery lesions (CALs) over one month after the KD onset. The incidence of CAL in patients who received corticosteroid during the disease course (10/37; 27.0%) was higher than that in those who did not (14/1450; 0.97%, p < 2.0 × 10 − 35 ). Nine patients who responded to initial IVIG plus corticosteroids had no CAL. Conversely, IVIG-resistant patients with alternate corticosteroid therapy more frequently developed CAL than those without it (10/28; 35.7% vs. 5/194; 2.6%, p < 8.9 × 10 − 10 ). Multivariate analyses indicated corticosteroid therapy (p < 0.0001), hyperbilirubinemia (p = 0.0010), and a longer number of days before treatment (p = 0.0005) as risk factors associated with CAL over a month after onset. The odds ratio of corticosteroid use increased from 18.3 to 43.5 if the cases were limited to initial IVIG non-responders and corticosteroid free-IVIG responders. Conclusions IVIG-failure has recently increased. The incidence of CAL increased in intractable cases with prolonged corticosteroid use. Corticosteroid may not be alternate choice for IVIG-failure to reduce the risk of cardiac sequelae.
Kawasaki disease (KD) is a systemic vasculitis of unknown etiology. The innate immune system is involved in its pathophysiology at the acute phase. We have recently established a novel murine model ...of KD coronary arteritis by oral administration of a synthetic microbe-associated molecular pattern (MAMP). On the hypothesis that specific MAMPs exist in KD sera, we have searched them to identify KD-specific molecules and to assess the pathogenesis.
We performed liquid chromatography-mass spectrometry (LC-MS) analysis of fractionated serum samples from 117 patients with KD and 106 controls. Microbiological and LC-MS evaluation of biofilm samples were also performed.
KD samples elicited proinflammatory cytokine responses from human coronary artery endothelial cells (HCAECs). By LC-MS analysis of KD serum samples collected at 3 different periods, we detected a variety of KD-specific molecules in the lipophilic fractions that showed distinct m/z and MS/MS fragmentation patterns in each cluster. Serum KD-specific molecules showed m/z and MS/MS fragmentation patterns almost identical to those of MAMPs obtained from the biofilms formed in vitro (common MAMPs from Bacillus cereus, Yersinia pseudotuberculosis and Staphylococcus aureus) at the 1st study period, and from the biofilms formed in vivo (common MAMPs from Bacillus cereus, Bacillus subtilis/Bacillus cereus/Yersinia pseudotuberculosis and Staphylococcus aureus) at the 2nd and 3rd periods. The biofilm extracts from Bacillus cereus, Bacillus subtilis, Yersinia pseudotuberculosis and Staphylococcus aureus also induced proinflammatory cytokines by HCAECs. By the experiments with IgG affinity chromatography, some of these serum KD-specific molecules bound to IgG.
We herein conclude that serum KD-specific molecules were mostly derived from biofilms and possessed molecular structures common to MAMPs from Bacillus cereus, Bacillus subtilis, Yersinia pseudotuberculosis and Staphylococcus aureus. Discovery of these KD-specific molecules might offer novel insight into the diagnosis and management of KD as well as its pathogenesis.
Preterm low-birth-weight infants remain difficult to manage based on adequate laboratory tests. The aim of this study was to establish blood reference intervals (RIs) in those newborns who were ...admitted to and survived in the neonatal intensive care unit (NICU). A multicenter prospective study was conducted among all infants admitted to 11 affiliated NICUs from 2010 to 2013. The clinical information and laboratory data were registered in a network database designed for this study. The RIs for 26 items were derived using the parametric method after applying the latent abnormal values exclusion method. The influence of birth weight (BW) and gestational age (GA) on the test results was expressed in terms of the standard deviation ratio (SDR), as SDRBW and SDRGA, respectively. A total of 3189 infants were admitted during the study period; 246 were excluded due to a lack of blood sampling data, and 234 were excluded for chromosomal abnormalities (n = 108), congenital anomalies requiring treatment with surgical procedures (n = 76), and death or transfer to another hospital (n = 50). As a result, 2709 infants were enrolled in this study. Both the SDRGA and SDRBW were above 0.4 in the test results for total protein (TP), albumin (ALB), alanine aminotransferase (ALT), and red blood cells (RBC); their values increased in proportion to the BW and GA. We derived 26 blood RIs for infants who were admitted to NICUs. These RIs should help in the performance of proper clinical assessments and research in the field of perinatal-neonatal medicine.
To investigate the hematological features of infants with bronchopulmonary dysplasia (BPD) and their relationships with clinical severity.
This prospective observational study enrolled 73 BPD ...patients from a total of 331 infants with a birth weight of <1500 g from 2005 to 2013. The clinical severity of BPD was defined by the duration of oxygen supplementation and positive pressure ventilation (PPV) in line with the diagnostic criteria of BPD. The hematological status and cytokine levels were surveyed from blood samples at birth and at 2 and 4 weeks of life.
Thirty-four (46.6%) cases were classified as "moderate-to-severe" BPD. Small-for-gestational-age (SGA) was associated with the severity of BPD (OR: 5.05; 95% CI: 1.45 to 17.2). The CRP level at 2 weeks (partial regression coefficient rc: 21.8; 4.01 to 39.7) and the neutrophil count at 4 weeks (0.005; 0.001 to 0.007) were positively correlated with the oxygenation period. The PPV period was found to be correlated with the CRP level at 2 weeks (27.2; 14.9 to 39.5), and the neutrophil count (0.003; 0.001 to 0.004) at 4 weeks.
The aggravation of BPD was associated with both SGA at birth and inflammation during neonatal period.
The early diagnosis of inherited thrombophilia in children is challenging because of the rarity and hemostatic maturation.
We explored protein C (PC), protein S (PS), and antithrombin (AT) ...deficiencies in 306 thromboembolic patients aged ≤20 y using the screening of plasma activity and genetic analysis.
Reduced activities were determined in 122 patients (40%). Low PC patients were most frequently found in the lowest age group (0-2 y, 45%), while low PS or low AT patients were found in the highest age group (16-20 y; PS: 30% and AT: 20%). Genetic study was completed in 62 patients having no other causes of thromboembolism. Mutations were determined in 18 patients (8 PC, 8 PS, and 2 AT genes). Six of eight patients with PC gene mutation were found in age 0-2 y (75%), while six of eight patients with PS gene mutation were in 7-20 y. Two AT gene-mutated patients were older than 4 y. Four PC-deficient and two PS-deficient patients carried compound heterozygous mutations. All but one PC gene-mutated patient suffered from intracranial thromboembolism, while PS/AT gene-mutated patients mostly developed extracranial venous thromboembolism.
Stroke in low PC infants and deep vein thrombosis in low PS/AT school age children could be targeted for genetic screening of pediatric thrombophilias.
A 36-year-old woman developed hypokalemic metabolic alkalosis after anti SS-A antibody was found to be positive. Diuretic loading test results were compatible with Gitelman syndrome (GS). The patient ...had a heterozygous mutation in SLC12A3, which encodes for thiazide-sensitive NaCl cotransporter (NCCT). While the mutation may be responsible for a latent hypofunction of NCCTs, the underlying anti-SSA antibody-associated autoimmunity induced the manifestation of its hypofunction. To the best of our knowledge, this is the first report to demonstrate that anti SS-A antibody-associated autoimmunity may induce GS in a patient with a SLC12A3 heterozygous mutation.
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