Wide-Targeted Semi-Quantitative Analysis of Acidic Glycosphingolipids in Cell Lines and Urine to Develop Potential Screening Biomarkers for Renal Cell Carcinoma.

Glycosphingolipids (GSLs), mainly located in the cell membrane, play various roles in cancer cell function. GSLs have potential as renal cell carcinoma (RCC) biomarkers; however, their analysis in body fluids is challenging because of the complexity of numerous glycans and ceramides. Therefore, we applied wide-targeted lipidomics using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with selected reaction monitoring (SRM) based on theoretical mass to perform a comprehensive measurement of GSLs and evaluate their potency as urinary biomarkers. In semi-quantitative lipidomics, 240 SRM transitions were set based on the reported/speculated structures. We verified the feasibility of measuring GSLs in cells and medium and found that disialosyl globopentaosylceramide (DSGb5 (d18:1/16:0)) increased GSL in the ACHN medium. LC-MS/MS analysis of urine samples from clear cell RCC (ccRCC) patients and healthy controls showed a significant increase in the peak intensity of urinary DSGb5 (d18:1/16:0) in the ccRCC group compared with that in the control group. Receiver operating characteristic analysis indicated that urinary DSGb5 could serve as a sensitive and specific marker for RCC screening, with an AUC of 0.89. This study demonstrated the possibility of urinary screening using DSGb5 (d18:1/16:0). In conclusion, urinary DSGb5 (d18:1/16:0) was a potential biomarker for cancer screening, which could contribute to the treatment of RCC patients.

Relationship of cerebral blood volume with arterial and venous flow velocities in extremely low-birth-weight infants.

Unstable cerebral blood flow is theorised to contribute to the occurrence of intraventricular haemorrhage (IVH) in extremely low-birth-weight infants (ELBWIs), which can be caused by increased arterial flow, increased venous pressure, and impaired autoregulation of brain vasculature. As a preliminary step to investigate such instability, we aimed to check for correlations of cerebral blood volume (CBV), as measured using near-infrared spectroscopy, with the flow velocities of the anterior cerebral artery (ACA) and internal cerebral vein (ICV), as measured using Doppler ultrasonography. Data were retrospectively analysed from 30 ELBWIs uncomplicated by symptomatic patent ductus arteriosus, which can influence ACA velocity, and severe IVH (grade ≥ 3), which can influence ICV velocity and CBV. The correlation between tissue oxygen saturation (StO2) and mean blood pressure was also analysed as an index of autoregulation. CBV was not associated with ACA velocity; however, it was significantly correlated with ICV velocity (Pearson R = 0.59 [95% confidence interval: 0.29-0.78], P = 0.00061). No correlation between StO2 and mean blood pressure was observed, implying that autoregulation was not impaired.    Conclusion: Although our findings are based on the premise that cerebral autoregulation was unimpaired in the ELBWIs without complications, the same result cannot be directly applied to severe IVH cases. However, our results may aid future research on IVH prediction by investigating the changes in CBV when severe IVH occurs during ICV velocity fluctuation. What is Known: • The pathogenesis of IVH includes unstable cerebral blood flow affected by increased arterial flow, increased venous pressure, and impaired cerebral autoregulation. • The approaches that can predict IVH are under discussion. What is New: • ACA velocity is not associated with CBV, but ICV velocity is significantly correlated with CBV. • CBV measured using NIRS may be useful in future research on IVH prediction.

Brain injury following mild hypoxic-ischemic encephalopathy in neonates-Ten-year experience in a tertiary perinatal center.

OBJECTIVE: We aimed to evaluate abnormal magnetic resonance imaging (MRI) findings in neonates with mild hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: This was a single-center, retrospective study of mild HIE conducted from 2011 to 2020. Almost all neonates with mild HIE received management targeted to a temperature of 36 ± 0.5°C for 72 h and underwent MRI (135 of 145). We evaluated medical records and assessed amplitude-integrated electroencephalography (aEEG). RESULT: All participants survived until discharge. Abnormal MRI findings were present in 23/135 (17%) neonates. The normal versus abnormal MRI-finding groups had similar characteristics, except discontinuous aEEG patterns (p = 0.002) and inotropic drugs (p = 0.035). Regression analyses showed discontinuous aEEG patterns (odds ratio = 19.3, 95% confidence interval=1.88-197, p = 0.013) being associated with higher odds of abnormal MRI findings. CONCLUSION: Our study suggests that a discontinuous aEEG pattern is associated with abnormal MRI findings and can be used to discuss the definition of mild HIE.

Fetal-onset malignant rhabdoid tumor: a case report.

BACKGROUND: A fetal-onset cervical mass may cause postnatal airway obstruction, and ex utero intrapartum treatment (EXIT) to secure the airway while maintaining fetal-placental circulation may be life-saving. Malignant rhabdoid tumors (MRT) are highly aggressive tumors, and when they develop in utero, the prognosis is even worse, with almost no reports of survival beyond the neonatal period. Herein, we report a case of a primary cervical MRT and describe our treatment using EXIT for securing the airway, wherein the infant's life was saved. CASE PRESENTATION: A 40-year-old Japanese woman with no relevant medical or surgical history was diagnosed with a fetal left cervical mass and polyhydramnios during the third trimester. Fetal magnetic resonance imaging indicated the possibility of postnatal airway obstruction, and delivery using EXIT was planned. The infant was delivered by a planned cesarean section at 39 weeks and 5 days gestation, and tracheostomy was performed using EXIT. Postnatal contrast-enhanced computed tomography revealed suspected metastatic lesions in the subcutaneous tissue, lungs, and thymus, in addition to the mass in the left cervical region. MRT was diagnosed by biopsy of a subcutaneous mass in the left thigh, and chemotherapy with vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide was initiated. The tumors regressed, and the infant was successfully weaned from artificial ventilation. After discharge from the hospital, she had a recurrent cervical mass and intracranial metastasis, and radiotherapy was initiated. CONCLUSIONS: In our case, fetal diagnosis enabled advance planning of delivery using EXIT, thus saving the infant's life. The use of chemotherapy for MRT, which has a poor prognosis, allowed tumor regression and enabled the infant to survive beyond the neonatal period.

The Relationship between Serum Total Bilirubin and Severity of Hypoxic Injury in Neonatal Hypoxic-Ischemic Encephalopathy.

INTRODUCTION: Bilirubin has been found to be a natural antioxidant protecting the body from oxidative stress. This study aims to investigate the severity of neonatal hypoxic injury on bilirubin levels to clarify the physiological role of bilirubin. STUDY DESIGN: Using lactate as a biomarker for the severity of hypoxic injury, we retrospectively analyzed the association of admission lactate levels on serum total bilirubin (TB) levels following birth in neonates with hypoxic-ischemic encephalopathy (HIE). We created a univariate linear regression model to predict TB using the admission lactate level as a predictor. We also performed a multivariate linear regression analysis to predict TB with admission lactate levels that included phenobarbital cumulative dosage, admission hematocrit, and subgaleal hemorrhage as predictor variables. RESULTS: A total of 86 patients were studied. Admission lactate levels had a significant negative effect on TB from admission to 3 days of life. The standardized regression coefficient for admission lactate on TB was -0.37 (admission), -0.42 (day 1), -0.32 (day 2), and -0.28 (day 3). A similar negative effect of admission lactate on TB levels was also observed in the multivariate linear regression model even after controlling for the other variables. CONCLUSION: These results are consistent with the hypothesis that bilirubin functions as an antioxidant in vivo, and is consumed by scavenging free radicals in proportion to the severity of hypoxic injury. KEY POINTS: · Lactate levels have a negative effect on serum TB levels in patients with neonatal HIE.. · Bilirubin might work as a natural antioxidant to protect the body from oxidative stress.. · Serum TB might be a marker for the severity of hypoxic injury..