Faculty Bibliography

OBJECTIVE: To evaluate the safety, efficiency, cost effectiveness, and satisfaction of patients undergoing cochlear implantation under conscious sedation versus general anesthesia. STUDY DESIGN: Retrospective case review of 20 patients who underwent cochlear implantation under conscious sedation which was compared to 20 age-matched patients where surgery was performed under general anesthesia. METHODS: Perioperative times, length of stay, anesthesia drug costs, postoperative complications, and patient satisfaction were compared between the two groups. RESULTS: Conscious sedation was associated with decreased drug costs, surgery time, and anesthesia time. Length of stay was significantly longer for patients undergoing general anesthesia. Patient satisfaction was superior with conscious sedation. Perioperative morbidity was not significantly different between the two groups. CONCLUSION: Conscious sedation for cochlear implantation is a safe, efficient, and cost-effective alternative to general anesthesia. The efficacy of conscious sedation for cochlear implant surgery may expand the treatment of profound hearing loss to the elderly who are deemed too sick for general anesthesia or are fearful of the cognitive or medical consequences of general anesthesia.

Low-grade astrocytomas (LGAs) carry neomorphic mutations in isocitrate dehydrogenase (IDH) concurrently with P53 and ATRX loss. To model LGA formation, we introduced R132H IDH1, P53 shRNA, and ATRX shRNA into human neural stem cells (NSCs). These oncogenic hits blocked NSC differentiation, increased invasiveness in vivo, and led to a DNA methylation and transcriptional profile resembling IDH1 mutant human LGAs. The differentiation block was caused by transcriptional silencing of the transcription factor SOX2 secondary to disassociation of its promoter from a putative enhancer. This occurred because of reduced binding of the chromatin organizer CTCF to its DNA motifs and disrupted chromatin looping. Our human model of IDH mutant LGA formation implicates impaired NSC differentiation because of repression of SOX2 as an early driver of gliomagenesis.

A guide to medications inducing salivary gland dysfunction, xerostomia and subjective sialorrhea: A systematic review sponsored by the World Workshop on Oral Medicine VI Background – Medication-induced salivary gland dysfunction (MISGD), xerostomia (sensation of oral dryness) and subjective sialorrhea cause significant morbidity and impair quality of life. However, evidence-based lists of medications that cause these disorders do not exist. Objective – To compile a list of medications affecting salivary gland function and inducing xerostomia or subjective sialorrhea. Data Sources – Electronic databases were searched for relevant articles published until June 2013. Data Synthesis – A total of 269 papers out of a total of 3867 screened records had an acceptable degree of relevance, quality of methodology and strength of evidence. We found 56 chemical substances with higher level of evidence and 50 with a moderate level of evidence of causing the above mentioned disorders. At the first level of the Anatomical Therapeutic Chemical classification system (ATC), 9 out of 14 anatomical groups were represented, mainly the alimentary, cardiovascular, genitourinary, nervous and respiratory systems. Management strategies include substitution or discontinuation of medications whenever possible, oral or systemic therapy with sialogogues, administration of saliva substitutes, and use of electro-stimulating devices. Limitations – While xerostomia was a commonly reported outcome, objectively measured salivary flow rate was rarely reported. Moreover, xerostomia was mostly assessed as an adverse effect rather than the primary outcome of medication use. This study may not include some medications that could cause xerostomia when given in conjunction with others or for which xerostomia as an adverse reaction has not been reported in the literature or not detected in our search. Conclusions – A comprehensive list of medications having documented effects on salivary gland function or symptoms was compiled, which may assist practitioners in assessing patients who complain of dry mouth while taking medications. The list may also prove useful for anticipating adverse effects and help practitioners to consider alternative medications

PURPOSE: Lower grade gliomas (WHO grade II/III) have been classified into clinically-relevant molecular subtypes based on IDH and 1p/19q mutation status. The purpose was to investigate whether T2/FLAIR MRI features could distinguish between lower grade glioma molecular subtypes

Experimental Design: MRI scans from the TCGA/TCIA lower grade glioma database (n=125) were evaluated by 2 independent neuroradiologists to assess: 1) presence/absence of homogenous signal on T2WI; 2) presence/absence of "T2-FLAIR mismatch" sign; 3) sharp or indistinct lesion margins; 4) presence/absence of peritumoral edema. Metrics with moderate-substantial agreement underwent consensus review, and were correlated with glioma molecular subtypes. Somatic mutation, DNA copy number, DNA methylation, gene expression, and protein array data from the TCGA lower grade glioma database were analyzed for molecular-radiographic associations. A separate institutional cohort (n=82) was analyzed to validate the T2-FLAIR mismatch sign.

Results: Among TCGA/TCIA cases, inter-reader agreement was calculated for lesion homogeneity (k=0.234 [0.111-0.358]), T2-FLAIR mismatch sign (k=0.728 [0.538-0.918]), lesion margins (k=0.292 [0.135-0.449]), and peritumoral edema (k=0.173 [0.096-0.250]). All 15 cases that were positive for the T2-FLAIR mismatch sign were IDH-mutant, 1p/19q-non-codeleted tumors (p<0.0001; PPV=100%, NPV=54%). Analysis of the validation cohort demonstrated substantial inter-reader agreement for the T2-FLAIR mismatch sign (k=0.747 [0.536 - 0.958]); all 10 cases positive for the T2-FLAIR mismatch sign were IDH-mutant, 1p/19q non-codeleted tumors (p<0.00001; PPV=100%, NPV=76%).

Conclusion: Among lower grade gliomas, T2-FLAIR mismatch sign represents a highly specific imaging biomarker for the IDH-mutant, 1p/19q-non-codeleted molecular subtype.