Fritz Teping

This investigation assesses the functionality, diagnostic efficacy, and limitations of a portable phased-array ultrasound apparatus in pediatric neurosurgical applications within a resource-constrained environment in Mombasa, Kenya. The ultrasound device was integrated into four neurosurgical missions conducted under the auspices of the SAWUBONA Foundation between 2021–2023. A retrospective analysis was performed on the diagnosed cases. Systematic training was provided to local neurosurgeons to enable autonomous operation of the device. Three representative cases were selected to elucidate the device's utility and constraints. The device was incorporated into the diagnostic and therapeutic regimens for 29 pediatric patients, culminating in 30 surgical interventions. Its diagnostic applicability was primarily confined to pediatric patients below one year of age, with a focus on hydrocephalus management. The apparatus consistently yielded sufficient data for discriminating between shunt placement and endoscopic third ventriculostomy. Its portability rendered it highly valuable across multiple healthcare settings, including outpatient clinics, surgical theaters, and inpatient wards. The educational initiative demonstrated a rapid learning curve among local healthcare professionals, enabling them to independently conduct examinations. The portable phased-array ultrasound device exhibited considerable diagnostic precision, particularly in the assessment and management of hydrocephalic conditions among pediatric patients within their first year of life. Its compact design and user-friendliness position it as a viable instrument for resource-limited environments and for educational enhancement in developing countries.

Objective: Epigenetic tumor characteristics are in focus for glioblastoma prognosis. This raises the question if these characteristics present with stable expression during the progression of the disease, and if potential temporal instability might influence their prognostic value. Methods: A total of 44 patients suffering from glioblastoma who were treated for their primary and relapse tumors were included in the study. Tumor specimens from the initial and recurrent tumor resection were subjected to evaluation of MGMT, p15, and p16 methylation statuses. MiRNA-21, -24, -26a, and -181d expression was evaluated as well. The stability of these epigenetic markers during the progression of the disease was correlated with further clinical data. A Cancer Genome Atlas (TCGA) dataset of 224 glioblastoma patients was used as an independent cohort to validate the results. Results: Instability was observed in all examined epigenetic markers. MGMT methylation changed in 30% of patients, p15 methylation changed in 35%, and p16 methylation changed in 37.5% of cases. MiRNA expression in corresponding initial and relapse tumor specimens varied considerably in general, individual cases presented with a stable expression. Patients with a decreased expression of miRNA-21 in their recurrence tumor showed significantly longer overall survival. These results are supported by the data from TCGA indicating similar results. Conclusions: Epigenetic characteristics may change during the course of glioblastoma disease. This may influence the prognostic value of derived molecular markers.

Background: Recently, miRNA-181a2 could be identified as a major regulator of IDH1 expression in fat tissue. The IDH1 gene, its mutation and expression have a major impact on overall survival in patients with glioblastoma. The presented study aimed to investigate the effect of miRNA-181a2 on IDH1 expression in glioblastoma and on the prognosis of patients suffering from, for example, a tumor. Methods: A total of 74 glioblastoma specimens were analyzed for the expression of miRNA-181a2, acquired as fold change, using qRT-PCR. IDH1 protein expression was estimated via mRNA quantification. Eight post mortal, non-glioma related brain tissue specimens served as the control group. The results were correlated with relevant demographic and clinical aspects of the cohort. A TCGA dataset was used as an independent reference. Results: MiRNA-181a2 was significantly downregulated in tumor samples compared to the control group (p < 0.001). In the glioblastoma cohort, 63/74 (85.1%) showed an IDH1 wild type, while 11/74 (14.9%) patients harbored an IDH 1 mutation. In patients with IDH1 wild type glioblastoma, low miRNA-181a2 expression correlated with a prolonged overall survival (p = 0.019), also verifiable in an independent TCGA dataset. This correlation could not be identified for patients with an IDH1 mutation. MiRNA-181a2 expression tended to correlate inversely with IDH1 protein expression (p = 0.06). Gross total resection of the tumor was an independent marker for a prolonged survival (p = 0.03). Conclusion: MiRNA-181a2 seems to be a promising prognostic marker of selective glioblastoma patients with IDH1 wild type characteristics. This effect may be mediated via direct regulation of IDH1 expression.