Case of metastatic glioblastoma with primitive neuronal component to the lung

Glioblastoma (GBM) with primitive neuronal component (GBM‐PNC) is a rare GBM subtype recently categorized by the World Health Organization in the revised classification system of 2016. Extracranial metastases originating from GBM‐PNC are rare and metastasis to solid organs has never been reported. Herein, we present the first case of metastasis of GBM‐PNC to the lung. A 49‐year‐old man presenting with headache was diagnosed with multiple tumors adhering to the dura matter in the right temporal lobe. Despite surgery and chemoradiotherapy, 2 months after the initial therapy, the patient presented with CSF dissemination and lung metastases. The patient succumbed to the disease 12 months after the first surgery. We discuss the possibility that GBM‐PNC may constitute a subtype of glioma with particularly poor prognosis, tending to dissemination and metastasis. Our results suggest that a complementary regular inspection of the whole body via CT may be recommended for the follow‐up of patients with GBM‐ PNC.     

Genetic testing has the potential to impact hearing preservation following cochlear implantation

Abstract

Background: Recent advances in less-invasive surgery and electrode design allow for a high degree of hearing preservation (HP) after cochlear implantation (CI), although residual hearing still deteriorates in some patients. To date, the factors predictive of preserving residual hearing remain a controversial topic.

Objective: The aim of this study was to investigate the predictive factors, including the etiology of hearing loss (HL) as a patient-related factor, influencing residual HP after CI.

Methods: Forty-four patients (50 ears, 41 families) with residual acoustic hearing who underwent CI were included. Auditory thresholds before and at 6 months after initial activation were measured. Genetic testing was performed to identify the responsible genes for HL.

Results: We identified the cause of HL in 21 families (51.2%). HP was marginally correlated with age at implantation, while it was independent of pre-operative low-frequency hearing thresholds, cochlear duct length, and electrode length. We found that patients who had pathogenic variants in the CDH23, MYO7A, or MYO15A gene showed statistically better HP scores compared with patients with HL due to other causes (p?=?.002).

Conclusions: Identification of the etiology of HL using genetic testing is likely to facilitate the prediction of HP after implant surgery.     

Prediction of human pharmacokinetics of typical compounds by a physiologically based method using chimeric mice with humanized liver

1. In this study, total body clearance (CL_t), volume of distribution at steady state (V_ss) and plasma concentration–time profiles in humans of model compounds were predicted using chimeric mice with humanized livers.

2. On the basis of assumption that unbound intrinsic clearance (CL_Uint) per liver weight in chimeric mice was equal to those in humans, CL_t were predicted by substituting human liver blood flow and liver weights in well-stirred model. V_ss were predicted by Rodgers equation using scaling factors of tissue-plasma concentration ratios (SF_Kp) in chimeric mice estimated from a difference between the observed and predicted V_ss. These physiological approaches showed high prediction accuracy for CL_t and V_ss values in humans.

3. We compared the predictability of CL_t and V_ss determined by the physiologically based predictive approach using chimeric mice with those from predictive methods reported by Pharmaceutical Research Manufacturers of America. The physiological approach using chimeric mice indicated the best prediction accuracy in each predictive method.

4. Simulation of human plasma concentration–time profiles were generally successful with physiologically based pharmacokinetic (PBPK) model incorporating CL_Uint and SF_Kp obtained from chimeric mice.

5. Combined application of chimeric mice and PBPK modeling is effective for prediction of human PK in various compounds.