Necrotizing apoptosis-related genes prognosis and treatment effect analysis of osteosarcoma in children.

BACKGROUND: Immune cell homeostasis plays a crucial role in cancer research and therapeutic response. While chemotherapy and immunotherapy hold promise in treating osteosarcoma (OS), identifying patients who are likely to respond would significantly improve clinical practices. Necroptosis, a fundamental mechanism mediating chemotherapy and immunotherapy efficacy, offers valuable insights. In this context, subtypes based on necroptosis-related genes have been established to predict the response of OS patients to immunotherapy and chemotherapy. METHODS: We conducted a high-throughput screening test to identify necroptosis-associated genes that regulate the development of osteosarcoma. Subsequently, the ConsensusClusterPlus package was employed to classify OS patients into subtypes, enabling comparisons of prognosis and clinical information between these subtypes. Patients from the TARGET-OS and GSE21257 datasets were stratified into high-risk and low-risk groups, and their prognoses were compared. Additionally, we assessed the accuracy of the Risk Scoring Model in predicting prognosis, identified independent prognostic factors and explored potential chemotherapeutic agents and immunotherapy drugs. RESULTS: Through the intersection of expression profiles from the TARGET-OS and GSE21257 datasets, we have identified a total of 92 genes associated with necroptosis. Based on differences in the expression of these genes, patients were divided into three subtypes, and we investigated the differences in tumor-infiltrating immune cells, immune-related pathways, and prognosis among these subtypes. Our nomogram effectively differentiated subtypes with distinct responses to chemotherapy and immunotherapy. The established signature demonstrated superior prediction ability compared with single clinical indicators. CONCLUSIONS: This pioneering study unveils the prognostic role of necroptosis-related genes in OS patients, providing a promising alternative for prognostic prediction in clinical disease management. Moreover, our findings highlight the significance of immune cell homeostasis in cancer research and therapeutic response, underscoring its relevance in advancing current treatment strategies.

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.

Feasibility and Reproducibility of Multifrequency Magnetic Resonance Elastography in Healthy and Diseased Pancreases.

BACKGROUND: The feasibility and reproducibility of multifrequency MR elastography (MRE) for diagnosing pancreatic ductal adenocarcinoma (PDAC) have not been reported. PURPOSE: To determine the feasibility and reproducibility of multifrequency MRE for assessing pancreatic stiffness in healthy and diseased pancreases. STUDY TYPE: Prospective. SUBJECTS: A total of 40 healthy volunteers and 10 patients with PDAC were prospectively recruited between March 2018 and October 2021. FIELD STRENGTH/SEQUENCE: A 3.0-T pancreatic MRE at frequencies in the order of 30, 40, 60, 80, and 100 Hz. ASSESSMENT: Body mass index (BMI) and wave distance of the healthy pancreas and PDAC were measured. Image quality was assessed using the image quality score (IQS: 1-4, ≥3 were considered diagnostic quality). Three readers independently performed the pancreatic stiffness and IQS assessments to evaluate reproducibility. STATISTICAL TESTS: Logistic regression analyses were performed to determine variables that influenced IQS. Statistical significance was set at P <0.05. Levels of inter- and intrarater agreement were assessed using intraclass correlation coefficients (ICC) and Cohen's kappa coefficient (κ). Good reproducibility was set at ICC and κ ≥ 0.8. RESULTS: In logistic regression analysis, a diagnostic IQS in healthy volunteers was independently associated with a lower BMI (odds ratio [OR] = 0.89 kg/m-2 ), shorter wave distance (OR = 0.70 cm-1 ), and lower frequency (30 and 40 Hz: OR = 170.01 and 96.02). In PDAC, frequency was the only independent factor for diagnostic IQS (30-60 Hz: OR = 46.18, 46.18, and 17.20, respectively) with 100 Hz as a reference. In healthy volunteers, good reproducibility was observed at 30 and 40 Hz. In PDAC, good reproducibility was observed at 30-60 Hz. DATA CONCLUSION: MRE at 30 and 40 Hz provides diagnostic wave images and reliable measurements of pancreatic stiffness in healthy volunteers. MRE at 30-60 Hz is acceptable for PDACs (IQS ≥ 3, ICC and κ ≥ 0.80). EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Clinical utility of 3D magnetic resonance elastography in patients with biliary obstruction.

OBJECTIVES: Three-dimensional magnetic resonance elastography (3D-MRE) allows for multiparametric modeling of both elastic and viscous tissue characteristics. Our aim was to compare 3D-MRE with conventional liver shear stiffness assessment in gauging obstructive jaundice (OJ), predicting the adequacy of biliary decompression after drainage, and discriminating OJ from liver fibrosis. METHODS: Patients with no histories of liver disease (n = 201) were studied in retrospect, grouped by bilirubin levels as no jaundice (NJ ≤ 2 mg/dL; n = 75), mild OJ (>2 mg/dL and ≤ 4 mg/dL; n = 56), and severe OJ (> 4 mg/dL; n = 70). For comparison, another 75 patients with chronic hepatitis B and C infections and histologically proven liver fibrosis were similarly analyzed. Each patient underwent spin-echo echo-planar-imaging MRE at 60 Hz with 3D wave postprocessing. Logistic regression and ordinary regression models were used to compare the 3D-MRE model with liver shear stiffness. RESULTS: Liver shear stiffness, loss modulus, and damping ratio were incorporated into a 3D-MRE model, which significantly outperformed shear stiffness in predicting OJ severity (accuracy: 0.801 vs 0.672; p < 0.001). Both the 3D-MRE model and liver shear stiffness performed equally well in predicting the outcome of biliary drainage procedure (C-statistics: 0.852 vs 0.847; p = 0.48). The 3D-MRE model also demonstrated significantly better C-statistics than that of liver shear stiffness in discriminating mild OJ from F1-F2 liver fibrosis (0.765 vs 0.641; p = 0.005) and severe OJ from F3-F4 liver fibrosis (0.750 vs 0.635; p = 0.031). CONCLUSIONS: 3D-MRE is an innovative imaging method for gauging OJ severity, predicting the outcome of biliary drainage procedure, and discriminating OJ from liver fibrosis. KEY POINTS: • 3D-MR elastography achieved promising results for predicting the severity of obstructive jaundice. • Advanced parameters of 3D-MR elastography demonstrated significantly better performance than that of shear stiffness of 2D-MR elastography in discriminating obstructive jaundice from liver fibrosis caused by chronic hepatitis B/C. • Both 3D-MR elastography and 2D-MR elastography were equivalent in predicting the outcome of biliary drainage procedure.

[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.

Multiregional Radiomic Signatures Based on Functional Parametric Maps from DCE-MRI for Preoperative Identification of Estrogen Receptor and Progesterone Receptor Status in Breast Cancer.

Radiomics based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has been used for breast estrogen receptor (ER) and progesterone receptor (PR) status evaluation. However, the radiomic features of peritumoral regions were not thoroughly analyzed. This study aimed to establish and validate the multiregional radiomic signatures (RSs) for the preoperative identification of the ER and PR status in breast cancer. A total of 443 patients with breast cancer were divided into training (n = 356) and validation (n = 87) sets. Radiomic features were extracted from intra- and peritumoral regions on six functional parametric maps from DCE-MRI. A two-sample t-test, least absolute shrinkage and selection operator regression, and stepwise were used for feature selections. Three RSs for predicting the ER and PR status were constructed using a logistic regression model based on selected intratumoral, peritumoral, and combined intra- and peritumoral radiomic features. The area under the receiver operator characteristic curve (AUC) was used to assess the discriminative performance of three RSs. The AUCs of intra- and peritumoral RSs for identifying the ER status were 0.828/0.791 and 0.755/0.733 in the training and validation sets, respectively. For predicting the PR status, intra- and peritumoral RSs resulted in AUCs of 0.816/0.749 and 0.806/0.708 in the training and validation sets, respectively. Multiregional RSs achieved the best AUCs among three RSs for evaluating the ER (0.851 and 0.833) and PR (0.848 and 0.763) status. In conclusion, multiregional RSs based on functional parametric maps from DCE-MRI showed promising results for preoperatively evaluating the ER and PR status in breast cancer patients. Further studies using a larger cohort from multiple centers are necessary to confirm the reliability of the established models before clinical application.

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.

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.

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.