Abstract Pediatric brain tumors affect more than 50,000 children in the US with nearly 5,000 new diagnoses annually. Although neurocognitive outcomes for this population show lower scores when compared to population means, there is great variability among individuals. In the current study, we aim to investigate the impact of cognition-related genes, KLOTHO, ApoE4, BDNF, COMT, and KIBRA, on neurocognitive outcomes in pediatric brain tumor patients. Utilizing an existing cohort of pediatric brain tumor patients from a diverse brain tumor population, we performed single nucleotide polymorphism (SNP) genotyping for KLOTHO, ApoE4, BDNF, COMT, and KIBRA. Neurocognitive evaluations were completed for these same patients at baseline and follow-up intervals, using validated, computer-based CogState batteries. Mixed modeling was done to correlate individual SNPs with neurocognitive outcomes over time, adjusting a priori for time from radiation, age at diagnosis, hydrocephalus, seizures, chemotherapy/radiation exposure, sex, tumor type, and tumor location. Lowess smoothing regression was done to assess the impact of individual genes SNPs on neurocognition. Ninety-seven patients were included in the analyses (54 males; median age at diagnosis 7 years). Medulloblastoma was the most frequent diagnosis (29%). Time from radiation, hydrocephalus at diagnosis, and seizures at diagnosis most consistently impacted neurocognition across neurocognitive test batteries (as based on statistical significance at p-value<0.05 across gene SNPs and testing batteries). Using smoothing regression, ApoE4 carrier status consistently negatively impacted neurocognitive function over time, as seen by decreasing neurocognitive scores over time across all batteries. Time from radiation and hydrocephalus and/or seizures at diagnosis illustrated statistically significant impacts on neurocognitive outcomes of pediatric brain tumor patients. KLOTHO, BDNF, COMT, and KIBRA did not appear to impact neurocognition; however, ApoE4 warrants further investigation as a possible predictor of neurocognitive outcomes. Our study highlights factors that may be of importance in anticipatory guidance and potentially, treatment-planning for children with brain tumors.

Abstract

OBJECTIVE

To identify genetic predictors of neurocognition, CMBs, brain volume, and WM changes in pediatric brain tumor survivors.

METHODS

Patients were selected from an existing cohort (RadART) if they had: 1) at least one neurocognitive evaluation using computer-based CogState; 2) available DNA; 3) standard imaging. Candidate gene or genome-wide genotyping was performed on all patients. CMBs were identified using a semi-automated algorithm developed in MATLAB. Volume of T2/FLAIR WM signal abnormality was measured using a semi-automated method based on a convolutional neural network. Brain volume and cortical thickness were measured using FreeSurfer volumetric analysis. Logistic and linear regression were done to compare phenotypes with candidate genotypes. Genome-wide efficient mixed-model analysis was done to compare neurocognition and CMBs. Gene set analysis was done using https://fuma.ctglab.nl/.

RESULTS

APOE4 was a candidate variant associated with non-lobar, larger volume CMBs (p< 0.05). At the GWAS-level (n=225), specific genes trended with visual memory, psychomotor function, and CMB count (p< 5x10-8). Using gene set analyses, there were gene set trends seen with CMB count and psychomotor function. Small sample size and low mutant allele frequency limited reliability of these findings. Preliminary volumetric analysis show reduced volume within the right parietal, medial occipital and inferior temporal lobes with increased cortical thickness in the left occipital and medial parietal lobe in patients carrying the ApoE4 allele. WM signal assessments are ongoing.

CONCLUSION

Genetic markers may be associated with neurocognition, CMBs, brain volume and WM changes in pediatric brain tumor survivors; however, larger cohorts are needed to confirm specific gene relevance.

Abstract

OBJECTIVE

To identify genetic predictors of neurocognition, CMBs, brain volume, and WM changes in pediatric brain tumor survivors.

METHODS

Patients were selected from an existing cohort (RadART) if they had: 1) at least one neurocognitive evaluation using computer-based CogState; 2) available DNA; 3) standard imaging. Candidate gene or genome-wide genotyping was performed on all patients. CMBs were identified using a semi-automated algorithm developed in MATLAB. Volume of T2/FLAIR WM signal abnormality was measured using a semi-automated method based on a convolutional neural network. Brain volume and cortical thickness were measured using FreeSurfer volumetric analysis. Logistic and linear regression were done to compare phenotypes with candidate genotypes. Genome-wide efficient mixed-model analysis was done to compare neurocognition and CMBs. Gene set analysis was done using https://fuma.ctglab.nl/.

RESULTS

APOE4 was a candidate variant associated with non-lobar, larger volume CMBs (p<0.05). At the GWAS-level (n=225), specific genes trended with visual memory, psychomotor function, and CMB count (p<5x10-8). Using gene set analyses, there were gene set trends seen with CMB count and psychomotor function. Small sample size and low mutant allele frequency limited reliability of these findings. Preliminary volumetric analysis show reduced volume within the right parietal, medial occipital and inferior temporal lobes with increased cortical thickness in the left occipital and medial parietal lobe in patients carrying the ApoE4 allele. WM signal assessments are ongoing.

CONCLUSION

Genetic markers may be associated with neurocognition, CMBs, brain volume and WM changes in pediatric brain tumor survivors; however, larger cohorts are needed to confirm specific gene relevance.

Objective

Surgical site infection (SSI) is a complication linked to increased costs and length of hospital stay. Prevention of SSI is important to reduce its burden on individual patients and the healthcare system. The authors aimed to assess the efficacy of preoperative chlorhexidine gluconate (CHG) showers on SSI rates following cranial surgery.

Methods

In November 2013, a preoperative CHG shower protocol was implemented at the authors' institution. A total of 3126 surgical procedures were analyzed, encompassing a time frame from April 2012 to April 2016. Cohorts before and after implementation of the CHG shower protocol were evaluated for differences in SSI rates.

Results

The overall SSI rate was 0.6%. No significant differences (p = 0.11) were observed between the rate of SSI of the 892 patients in the preimplementation cohort (0.2%) and that of the 2234 patients in the postimplementation cohort (0.8%). Following multivariable analysis, implementation of preoperative CHG showers was not associated with decreased SSI (adjusted OR 2.96, 95% CI 0.67-13.1; p = 0.15).

Conclusions

This is the largest study, according to sample size, to examine the association between CHG showers and SSI following craniotomy. CHG showers did not significantly alter the risk of SSI after a cranial procedure.