Indicators of Oxidative Stress in the Prediction of Coronary Artery Lesions in Patients With Kawasaki Disease.

OBJECTIVES: The aim of this study was to examine the clinical significance of oxidative stress (OS)-related indices, including inflammatory markers and lipid and platelet (PLT) parameter, in coronary artery lesions (CALs) in Kawasaki disease (KD). METHODS: Clinical data of 952 KD patients diagnosed between January 2019 and March 2022 were collected and divided into CAL and NCAL groups. All the KD patients were randomly divided into training set and verification set. The univariate analysis and multivariate logistic regression analysis of training set were used to identify the OS-related independent risk factors of CALs, which were then used to construct a predictive nomogram. Calibration curve and receiver operating characteristic curve were used to evaluate the performance of the model. The predictive nomogram was further validated on verification set. RESULTS: In the training set, 137 KD patients (18.0%) showed CALs. C-reactive protein, serum amyloid A, PLT count, monocyte-to-high-density lipoprotein (HDL) ratio, and PLT-to-lymphocyte ratio were significantly higher, whereas HDL was lower in the CAL group than the NCAL group. Increased C-reactive protein, serum amyloid A, PLT, and decreased HDL were identified as independent risk factors. The nomogram constructed using these factors showed satisfactory calibration degree and discriminatory power (the area under the curve, 0.887). In the verification set, the area under the curve was 0.795. CONCLUSION: The predictive nomogram constructed using 4 OS-related risk factors associated with CALs in patients with KD could be a useful tool for early diagnosis of CALs in KD.

Urate crystal deposition in hyperuricemic children: a dual energy computed tomography study.

INTRODUCTION: The incidence of hyperuricemia (HUA) at younger ages is increasing along the coastal regions of China. This study aimed to compare the frequency of dual energy CT (DECT) urate crystal deposition between symptomatic hyperuricemic children and asymptomatic hyperuricemic children. MATERIAL AND METHODS: Fifty-six hyperuricemic children were divided into a Joint Group (n = 33) and an Asymptomatic Group (n = 23) according to whether they had a history of arthritis symptoms, which includes rapid onset monoarthritis with intense pain and swelling. We analyzed DECT scans of their feet from the Joint Group and the Asymptomatic Group and compared their clinical features. RESULTS: DECT urate deposits were observed in 28/33 (84.8%) children with symptomatic HUA and 14/23 (60.9%) with asymptomatic HUA. We found 60 areas of urate deposition in the Joint Group; DECT urate crystal deposition was most frequently observed in the first metatarsophalangeal (MTP) joint (30.0%), ankle joint (15.0%), and calcaneus (13.3%). 39 urate deposits were found in the Asymptomatic Group; DECT urate crystal deposition was most frequently observed in the calcaneus (25.6%), the first MTP joint (17.9%), and the first phalanx (15.4%). CONCLUSIONS: Urate deposition can occur in children with HUA, and these deposits occur more frequently in hyperuricemic children with a history of arthritis symptoms. Also, the urate deposition in the first MTP joint and calcaneus was more prevalent than in other joints. It is important to give more attention to hyperuricemic children.

Elevated urinary monocyte chemoattractant protein-1 levels in children with Henoch-Schonlein purpura nephritis.

BACKGROUND: Chemokine monocyte chemoattractant protein-1 (MCP-1) has been proved as a potential urinary biomarker in nephropathies. The aim of this study was to investigate the urinary monocyte chemoattractant protein-1 (MCP-1) levels and clinical significance in Henoch-Schonlein purpura (HSP) children with and without nephritis and determine the association of MCP-1 with proteinuria. METHODS: A total of 261 HSP children-with or without nephritis-and 84 healthy control children were enrolled in this study. Of these, 126 HSP nephritis (HSPN) children were subdivided into three groups according to total urine protein in 24 h (TUP): Group A, mild proteinuria group with TUP <25 mg/kg; Group B, moderate proteinuria group with TUP ≥25 mg/kg and <50 mg/kg; Group C, severe proteinuria group with TUP ≥50 mg/kg. Urinary MCP-1 levels were determined by ELISA. Levels of serum creatinine (Cr), blood urea nitrogen (BUN), urinary α1-micro globulin (α1-MG), micro-albumin (mAlb), immunoglobulin G (IgG), transferrin (TRF) and TUP were performed to determine their associations with MCP-1. RESULTS: Urinary MCP-1 was significantly higher in HSPN group in comparison with HSP group and controls (P < 0.05), but no significant difference was found between the HSP group and the healthy group (P > 0.05). The levels of urinary MCP-1 increased in parallel to the enhancement of total urine protein in 24 h in HSPN patients. There were statistically significant differences among these three groups of HSPN children (p < 0.05). Urinary MCP-1 correlated positively with urinary α1-MG, mAlb, IgG, TRF and TUP in HSPN, whereas no correlation was observed with serum Cr and BUN. CONCLUSIONS: MCP-1 was elevated in children with HSPN and correlated with proteinuria. Urinary MCP-1 could be used as a suitable, non-invasive biomarker to provide valuable information not only for the diagnosis of HSPN, but also for evaluation of severity of renal damage.

Elevated Interleukin 1ß and Interleukin 6 Levels in the Serum of Children With Hyperuricemia.

PURPOSES: The aim of this study was to investigate the serum levels and clinical significance of interleukin 1ß (IL-1ß) and IL-6 in children with hyperuricemia (HUA). METHODS: We included 71 children with HUA and 71 children with no HUA as control subjects. Children with HUA were divided into groups I and II according to whether they had a history of acute gout-like attacks (including sudden monoarthritis of rapid onset with intense pain and swelling). Group I was examined twice (A, in the acute phase; B, in the remission phase). Serum IL-1ß and IL-6 levels were measured by enzyme-linked immunosorbent assay. RESULTS: Serum IL-1ß and IL-6 levels were increased in children with HUA and were overall statistically different from the control group (P < 0.05, respectively). Serum IL-1ß and IL-6 were significantly higher in group IA in comparison with group IB, group II, and control subjects (P < 0.05, respectively), as well as in groups IB and II compared with control subjects (P < 0.05, respectively). In group IB, the serum IL-1ß and IL-6 concentrations were higher than those in group II, but there were no statistical differences (P > 0.05). In addition, in children with HUA, serum IL-1ß and IL-6 levels were positively associated with white blood cell count, neutrophil count, monocyte count, uric acid levels, erythrocyte sedimentation rate, C-reactive protein, blood urea nitrogen, and serum creatinine levels (all P < 0.05), but were not associated with triglycerides, total cholesterol, low-density lipoprotein cholesterol, or high-density lipoprotein cholesterol levels (all P > 0.05). CONCLUSION: IL-1ß and IL-6 levels are increased in children with hyperuricemia, even if they have not had acute gout. Further studies are necessary to fully characterize the significance of IL-1ß and IL-6 found in HUA children, and whether they could be correlated with long-term prognosis.

[Values of fat saturation sequence in MRI for juvenile arthritis].

OBJECTIVE: To explore the values of fat saturation sequence in MRI for juvenile arthritis.
 Methods: A total of 1 131 cases with juvenile arthritis and 1 601 with symptomatic arthritis were examined by MRI normal T1 weighted imaging (T1WI) and T2 weighted imaging (T2WI) sequence and spectral presaturation attenuatedinversion recovery (SPAIR) T2 fat saturation sequence. All the images were independently evaluated by two senior doctors from the Department of Radiology and the Department of Pediatric Rheumatology and Immunology respectively to confirm the types and degree of pathological changes of joint tissues.
 Results: Among the subjects, 847 patients demonstrated positive in MRI, accounting for 52.9%; 409 patients showed positive in normal sequence, accounting for 48.3%; 816 patients showed positive in fat saturation sequence, accounting for 96.3%. Joint hydrops accounted for 59.5%. Bone marrow edema accounted for 39.7%. The relevant ratio of bone marrow edema, joint hydrops, thickening of synovium and cartilage injuries in fat saturation sequence were higher than that in normal sequence (P<0.05). The relevant ratio of bone erosion in normal sequence was higher than that in fat saturation sequence (P<0.05). However, no significant difference of joint cysts was found between the fat saturation sequence and normal sequence (P<0.05).
 Conclusion: Application of fat saturation sequence by MRI to check juvenile arthritis could obviously improve the positive MRI relevant ratio. In addition, the relevant ratio of the early pathological changes of juvenile arthritis (such as bone marrow edema and joint hydrops) was high, which might provide references for the early diagnosis of juvenile arthritis.

Urinary Macrophage Migration Inhibitory Factor as a Noninvasive Biomarker in Pediatric Henoch-Schönlein Purpura Nephritis.

PURPOSES: The aims of this study were to investigate urinary macrophage migration inhibitory factor (MIF) levels and their clinical significance in Henoch-Schönlein purpura (HSP) children with or without nephritis (N) and to assess the influence of steroid treatment on the urine MIF levels of HSPN patients. METHODS: Group I comprised 35 children with HSPN who were examined twice (A before treatment and B after steroid treatment). Group II comprised 41 children with HSP. The control group included 32 healthy children. Urinary MIF levels were measured via enzyme linked immunosorbent assay. The levels of serum creatinine, blood urea nitrogen, urinary microalbumin (mAlb), and 24-hour proteinuria were performed to determine their associations with MIF levels. RESULTS: Urinary MIF levels were significantly higher in group I compared with group II and the control group (P < 0.01); however, no significant difference was found between group II and the control group (P > 0.05). Upon examination, albeit urinary MIF concentration was significantly lower in group IB compared with group IA (P < 0.05), these concentrations were statistically higher than that of group II (P < 0.05). In addition, in the HSPN patients, the urinary MIF was positively associated with urinary microalbumin and 24-hour proteinuria but no association with serum creatinine and blood urea nitrogen. CONCLUSIONS: Elevated urinary MIF levels were found to be correlated with proteinuria in pediatric HSPN. An obvious decrease in urinary MIF concentrations among the children with HSPN was associated with steroid treatment. Urinary MIF can be used as a noninvasive biomarker in pediatric HSPN.

Sex-dichotomous effects of NOS1AP promoter DNA methylation on intracranial aneurysm and brain arteriovenous malformation.

The goal of this study was to investigate the contribution of NOS1AP-promoter DNA methylation to the risk of intracranial aneurysm (IA) and brain arteriovenous malformation (BAVM) in a Han Chinese population. A total of 48 patients with IAs, 22 patients with BAVMs, and 26 control individuals were enrolled in the study. DNA methylation was tested using bisulfite pyrosequencing technology. We detected significantly higher DNA methylation levels in BAVM patients than in IA patients based on the multiple testing correction (CpG4-5 methylation: 5.86±1.04% vs. 4.37±2.64%, P=0.006). In women, CpG4-5 methylation levels were much lower in IA patients (3.64±1.97%) than in BAVM patients (6.11±1.20%, P<0.0001). However, in men, CpG1-3 methylation levels were much higher in the controls (6.92±0.78%) than in BAVM patients (5.99±0.70%, P=0.008). Additionally, there was a gender-based difference in CpG1 methylation within the controls (men vs. women: 5.75±0.50% vs. 4.99±0.53%, P=0.003) and BAVM patients (men vs. women: 4.70±0.74% vs. 5.50±0.87%, P=0.026). A subgroup analysis revealed significantly higher CpG3 methylation in patients who smoked than in those who did not (P=0.041). Our results suggested that gender modulated the interaction between NOS1AP promoter DNA methylation in IA and BAVM patients. Our results also confirmed that regular tobacco smoking was associated with increased NOS1AP methylation in humans. Additional studies with larger sample sizes are required to replicate and extend these findings.

Urate crystals deposition in the feet of overweight juveniles and those with symptomatic hyperuricemia: a dual-energy CT study.

BACKGROUND: The present study evaluated the clinical value of dual-energy computed tomography (DECT) for detecting urate crystals in juveniles with symptomatic hyperuricemia. METHODS: We recruited 24 juveniles (15 male and 9 female) who presented with symptomatic hyperuricemia. The mean body mass index (BMI) was 26.4 kg/m2 (standard deviation, SD 11.3 kg/m2). Fifteen juveniles (71.4%) were overweight. DECT scans of the feet were performed. For post-processing, a color-coding gout software protocol was used. RESULTS: Urate crystals deposition was observed in 21/24 (87.5%) juveniles with symptomatic hyperuricemia. Urate crystals were detected in or around the anatomic site included the first metatarsophalangeal (MTP) joints (5/24, 20.8%); the calcaneus (5/24, 20.8%); any other toe joints (3/24, 12.5%); the astragalus (3/24, 12.5%); the ankle joints (3/24, 12.5%); the metatarsals (2/24, 8.3%); the cuboid (1/24, 4.2%); and other parts of the feet (2/24, 8.3%). Importantly, urate crystals deposition weas located in the soft tissue (tendon/tendon insertion sites/entheses) around the above-mentioned sites in a majority of these patients. CONCLUSIONS: Urate crystals deposition can be detected by dual-energy CT in the feet of symptomatic hyperuricemia juveniles. DECT can be a valuable diagnostic tool for helping diagnose in juvenile gout.

The Association between PTPN22 Genetic Polymorphism and Juvenile Idiopathic Arthritis (JIA) Susceptibility: An Updated Meta-Analysis.

BACKGROUND: Limited studies have focused on the association between the protein tyrosine phosphates non-receptor type 22 (PTPN22) genetic polymorphisms and Juvenile idiopathic arthritis (JIA) susceptibility in different populations, but the results were inconclusive. Therefore, this meta-analysis of PTPN22 polymorphism (1858 C>T) was performed to get a precise systematic estimation. The "rs" number of the PTPN22 polymorphism (1858 C>T) is 4. METHODS: A systematic literature search strategy was carried out using English databases (PubMed, Embase.) for the eligible studies. We ultimately identified 11 records from 10 articles involving the relationship between PTPN22 genetic polymorphisms and JIA risk from PubMed and Embase databases. Overall, 4552 cases and 10161 controls were investigated in this study to evaluate the association between PTPN22 (C allele vs. T allele) genotype and JIA susceptibility. RESULTS: Analysis using random effects model showed an increased risk of JIA with T allele of rs2476601 vs. A allele (P<0.001). Subgroup analysis suggested that the PTPN22 polymorphism (1858C>T) was significantly associated with JIA risk in America population (OR=1.52, 95% CI:1.30-1.78). Additionally, the subgroup analysis also showed that the associations were still significant in case number more than 500 (OR=1.38, 95% CI: 1.04-1.83), while in the case number less than 500 was OR=1.55, 95% CI: 1.39-1.72. CONCLUSIONS: SNPs of PTPN22 (1858C>T) showed an increased risk of developing JIA.

Blood N-terminal Pro-brain Natriuretic Peptide and Interleukin-17 for Distinguishing Incomplete Kawasaki Disease from Infectious Diseases.

OBJECTIVE: To explore the diagnostic value of blood N-terminal pro-brain natriuretic peptide (NT-proBNP) and interleukin-17(IL-17) for incomplete Kawasaki disease. METHODS: Patients with Kawasaki disease, Incomplete Kawasaki disease and unclear infectious fever were included in this retrospective study. Their clinical features, and laboratory test results of blood NT-proBNP and IL-17 were collected and compared. RESULTS: 766 patients with complete clinical information were recruited, consisting of 291 cases of Kawasaki disease, 74 cases of incomplete Kawasaki disease, and 401 cases of unclear infectious diseases. When the consistency with indicator 2 and 3 in Kawasaki disease diagnosis criteria was assessed with blood IL-17 ?11.55 pg/mL and blood NT-proBNP ? 225.5 pg/dL as the criteria, the sensitivity and specificity for distinguishing incomplete Kawasaki disease and infectious diseases reached 86.5% and 94.8%, respectively. When we chose the consistency with indicator 1 and 2 in Kawasaki disease diagnosis criteria, the appearance of decrustation and/or the BCG erythema, blood IL-17 ?11.55 pg/mL and blood NT-Pro BNP ?225.5 pg/dL as the criteria, the sensitivity and specificity for distinguishing incomplete Kawasaki disease and infectious diseases was 43.2% and 100%, respectively. CONCLUSIONS: Blood NT-proBNP and IL-17 are useful laboratory indicators for distinguishing incomplete Kawasaki disease and infectious diseases at the early stage.