Search

Introduction There is increasing concern regarding the risks associated with the use of general anesthesia in pediatric patients. Many otolaryngologic procedures performed under general anesthesia can also be performed in clinic. We hypothesize that anxiolytics can aid in performing common procedures in clinic thus avoiding the need to undergo general anesthesia in the OR. Methods We performed a retrospective review of patients undergoing inoffice procedures with anxiolytics in our pediatric otolaryngology outpatient clinic between February 2013 and January 2017. Charts were reviewed for age, past medical history, procedure type/duration, and outcome. These results were then compared to a cohort undergoing similar procedures in the OR. Results A total of 34 patients underwent an in-office procedure with an anxiolytic. The success rate was 97% (33/34). The average age was 6.2 years. Six children (17%) had a known history of chromosomal abnormalities and 2 children (6%) had autism. The four most common procedures performed were cerumen impaction removal (8), flexible laryngoscopy (6), ear canal foreign body removal (5), and septal cautery (4). Performing similar procedures in the OR resulted in an average additional cost of $822. Conclusions Performing procedures with anxiolytics in a pediatric otolaryngology clinic is safe, expeditious, and cost-effective. Anxiolytics can provide an effective alternative to general anesthesia.

HIV-associated vacuolar myelopathy, or AIDS-associated myelopathy, is a rare initial presentation of HIV. One of the common HIV-associated neurocognitive disorders, HIV-associated vacuolar myelopathy presents with advanced immunosuppression in patients and is frequently associated with dementia. However, most cases are subclinical with characteristic findings identified through physical examination and/or imaging modalities. HIV-associated vacuolar myelopathy is characterized by progressive spastic paraparesis, gait disturbance and lower extremity sensory abnormalities including vibratory sensation. Magnetic resonance imaging findings in the spinal cord are abnormal in some patients with HIV-associated myelopathy, characteristically showing spinal cord atrophy at the level of the thoracic spine, but they may also be normal. Unfamiliarity with this as initial presentation of HIV infection may lead to failure to diagnose and intervene appropriately. We present a case of newly diagnosed HIV with myelopathy and dementia with minimal spinal cord involvement on magnetic resonance imaging.

Functional and molecular cell-to-cell variability is pivotal at the cellular, tissue and whole-organism levels. Yet, the ultimate goal of directly correlating the function of the individual cell with its biomolecular profile remains elusive. We present a platform for integrated analysis of functional and transcriptional phenotypes in the same single cells. We investigated changes in the cellular respiration and gene expression diversity resulting from adaptation to repeated episodes of acute hypoxia in a premalignant progression model. We find differential, progression stage-specific alterations in phenotypic heterogeneity and identify cells with aberrant phenotypes. To our knowledge, this study is the first demonstration of an integrated approach to elucidate how heterogeneity at the transcriptional level manifests in the physiologic profile of individual cells in the context of disease progression.

In carcinogenesis, intercellular interactions within and between cell types are critical but remain poorly understood. We present a study on intercellular interactions between normal and premalignant epithelial cells and their functional relevance in the context of premalignant to malignant progression in Barrett’s esophagus. Using whole transcriptome profiling we found that in the presence of normal epithelial cells, dysplastic cells but not normal cells, exhibit marked down-regulation of a number of key signaling pathways, including the transforming growth factor beta (TGFβ) and epithelial growth factor (EGF). Functional assays revealed both cell types showed repressed proliferation and significant changes in motility (speed, displacement and directionality) as a result of interactions between the two cell types. Cellular interactions appear to be mediated through both direct cell-cell contact and secreted ligands. The findings of this study are important in that they reveal, for the first time, the effects of cellular communication on gene expression and cellular function between premalignant (dysplastic) epithelial cells and their normal counterparts.

Cell-cell communication plays a central role in cellular function under normal and diseased conditions. In cancer, intercellular interactions are highly complex and remain poorly understood, particularly with respect to the early events leading to the transformation from benign to malignant phenotypes. In early stages of carcinogenesis, normal and transformed cells often coexist in close proximity, suggesting that interactions between them influence progression. Comprehensive understanding of these events is critical in identifying new therapeutic targets and devising novel treatment strategies. We studied the functional relevance of intercellular interactions between normal and pre-malignant epithelial cells using an in vitro model of Barrett's esophagus (BE) progression from pre-malignant epithelium to esophageal adenocarcinoma. BE provides an ideal disease model to explore the interaction between cells at different stages of neoplastic transformation because it can be prospectively followed. Thus, studies performed in in vitro and animal models can be readily extended to the clinic. We investigated the effects of heterotypic interactions between normal and dysplastic (pre-malignant) esophageal epithelial cells at the single-cell and bulk-cell level. We found that the dysplastic cells were affected to a larger extent than normal cells in terms of gene expression levels and cellular function. Analysis of the RNA-seq data revealed a total of 809 genes differentially expressed in dysplastic cells as compared with 234 genes differentially expressed in normal cells. Functional enrichment analysis identified the following 5 top functional categories in dysplastic cells affected (downregulated) by interactions with normal epithelial cells: cellular movement, tissue morphology, cancer, lipid metabolism and molecular transport. Functional assays revealed a significant repression of the proliferation rates (up to 6-fold) of both cell types, but only dysplastic cells showed significant motility changes (speed, displacement and directionality) as a result of interactions between the two cell types. The decrease in the proliferation rate of dysplastic cells indicates a strong suppressor role of normal epithelial cells mediated by repression of TGFβ and EGF signaling in pre-malignant progression in BE. At the single-cell level, we present both metabolic and expression-level profiles of a panel of selected genes in individual normal and dysplastic cells, and compare them with bulk-cell measurements. These findings indicate that attenuation of the TGFβ and EGF signaling pathways in the presence of normal epithelial cells may play an important role in suppressing the growth of pre-malignant epithelial cells. Hence, both TGFβ and EGF may serve as biomarkers for progression from pre-malignant to malignant phenotype in epithelial cells. Citation Format: Laimonas Kelbauskas, Jia Zeng, Aida Rezaie, Kristen Lee, Benjamin Ueberroth, Weimin Gao, Dmitry Derkach, Colleen Ziegler, Thai Tran, Kimberly J. Bussey, Dean Smith, Roger H. Johnson, Deirdre R. Meldrum. Suppressive role of normal epithelium in pre-malignant to malignant progression of Barrett's esophagus. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4033. doi:10.1158/1538-7445.AM2015-4033