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Primary intracranial germ cell tumors are rare, occurring more frequently in children and young adults in midline locations of the brain. Teratomas are an uncommon variant of germ cell neoplasm, although they account for a high proportion of fetal brain tumors. Here, we report a 27-year-old male who presented with a heterogeneously enhancing lesion in the left thalamus, without evidence of systemic disease. Histologic and immunohistochemical analysis were consistent with immature teratoma; next-generation sequencing was negative for targetable molecular alterations. The patient received chemotherapy and radiotherapy post-excision. Following the initial resection, ventriculoperitoneal shunt placement was performed due to left temporal horn entrapment. Nine months later, imaging revealed mediastinal and hilar adenopathy as well as pleural disease, with encasement and compression of pulmonary vasculature, and multiple, bilateral pulmonary nodules. Fine needle aspiration showed malignant cells with an immunohistochemical profile similar to the original tumor, consistent with metastases. Though germ cell tumors are known to spread via cerebrospinal fluid or blood, metastasis outside of the CNS from a primary intracranial germ cell tumor is a rare complication. Spread via ventriculoperitoneal shunt, which may have occurred in the present case, has also rarely been observed.

BackgroundOfranergene obadenovec (VB-111) is an anticancer viral therapy that demonstrated in a phase II study a survival benefit for patients with recurrent glioblastoma (rGBM) who were primed with VB-111 monotherapy that was continued after progression with concomitant bevacizumab.MethodsThis pivotal phase III randomized, controlled trial compared the efficacy and safety of upfront combination of VB-111 and bevacizumab versus bevacizumab monotherapy. Patients were randomized 1:1 to receive VB-111 1013 viral particles every 8 weeks in combination with bevacizumab 10 mg/kg every 2 weeks (combination arm) or bevacizumab monotherapy (control arm). The primary endpoint was overall survival (OS), and secondary endpoints were objective response rate (ORR) by Response Assessment in Neuro-Oncology (RANO) criteria and progression-free survival (PFS).ResultsEnrolled were 256 patients at 57 sites. Median exposure to VB-111 was 4 months. The study did not meet its primary or secondary goals. Median OS was 6.8 versus 7.9 months in the combination versus control arm (hazard ratio, 1.20; 95% CI: 0.91-1.59; P = 0.19) and ORR was 27.3% versus 21.9% (P = 0.26). A higher rate of grades 3-5 adverse events was reported in the combination arm (67% vs 40%), mainly attributed to a higher rate of CNS and flu-like/fever events. Trends for improved survival with combination treatment were seen in the subgroup of patients with smaller tumors and in patients who had a posttreatment febrile reaction.ConclusionsIn this study, upfront concomitant administration of VB-111 and bevacizumab failed to improve outcomes in rGBM. Change of treatment regimen, with the lack of VB-111 monotherapy priming, may explain the differences from the favorable phase II results.Clinical trials registrationNCT02511405.

The gut microbiome influences neurological disorders through bidirectional communication between the gut and the brain, i.e., the gut-brain axis. Artemisia asiatica ex, an extract of Artemisia asiatica Nakai (Stillen®, DA-9601) has been reported to improve depression by increasing brain-derived neurotropic factor. Therefore, we hypothesized that DA-9601 can be a potential therapeutic candidate for Alzheimer's disease (AD) acting through the gut-brain axis. Four groups of Tg2576 mice were used as the animal model for AD: wild type mice (n = 6), AD mice (n = 6), and DA-9601-administered AD mice given dosages of 30mg/kg/day (DA_30mg; n = 6) or 100mg/kg/day (DA_100mg; n = 6). Microglial activation, blood‒brain barrier integrity, amyloid beta accumulation, cognitive behavior, and changes in the gut microbiome were analyzed. DA-9601 improved the cognitive behavior of mice (DA_30mg **p<0.01; DA_100mg **p<0.01) and reduced amyloid beta accumulation (DA_30mg ***p<0.001; DA_100mg **p<0.01). Increased Iba-1 and upregulation of claudin-5 (DA_30mg *p<0.05) and occludin (DA_30mg **p<0.01; DA_100mg ***p<0.001) indicated altered microglial activation and improved blood‒brain barrier integrity. Akkermansia muciniphila was dramatically increased by DA-9601 administration (DA_30mg 47%; DA_100mg 61%). DA-9601 improved AD pathology with Akkermansia muciniphila dominance in the gut microbiome in a mouse model of AD, inferring that DA-9601 can affect AD through the gut-brain axis. [ABSTRACT FROM AUTHOR]

Introduction: Informal caregivers, mostly family members or friends, have often been required to engage in medical/nursing tasks and to navigate complex healthcare systems. It is unclear whether those activities impact caregiver burden. Therefore, the purpose of this study was to examine predictive factors of caregiver burden in consideration of healthcare-related factors (caregivers' perception of performing medical/nursing tasks, care coordination, and number of hospitalizations). Methods: Secondary analysis of cross-sectional survey data taken from the Caregiving in the U.S. 2015 was conducted. Data were collected by the National Alliance for Caregiving and the American Association of Retired Persons (AARP). Self-identified caregivers (n = 304) who provided care for individuals with cognitive impairment (ICI), and who were living in the community were participants in the study. Results: The overall model explained 38.4% of the variance in caregiver burden (F = 20.48, p < 0.001). When examining each factor, perceived difficulty in medical/nursing tasks (β = 0.38, p < 0.001) was the most influential factor, followed by caregivers' physical health (β = −0.27, p < 0.001), income (β = −0.13, p = 0.01), and level of the care coordination (β = 0.12, p = 0.02). Discussion: Although caregivers' involvement in healthcare-related activities for ICI is necessary, this involvement has a considerable impact on caregiver burden. Healthcare providers should be cognizant of caregiver burden related to healthcare-related activities. Moreover, researchers should develop interventions and community services to decrease caregivers' difficulty in performing their roles. [ABSTRACT FROM AUTHOR]