Bozena Wrobel

Decreased nasal mucosal sensitivity in older subjects

Background The sensitivity of the human nasal cavity mucosa to touch is not well understood. The site of receptors and mode of action responsible for the sensation of the nasal airflow is a topic of controversy. Previous studies have suggested that the skin-lined nasal vestibule is more sensitive to airflow than the mucosa of the nasal cavity. A possible decline in nasal sensitivity to airflow in older subjects has not been studied. Methods The threshold of the mucosal sensitivity to jets of air was assessed in 76 subjects with healthy nasal cavities. A total of 141 nostrils were tested, 67 in younger patients and 74 in older patients. Results Statistically significant (p < 0.001) increases in thresholds were found for all points tested for older patients compared with the younger patients. In general, the more sensitive locations were in the nasal vestibule. The nasal cavity mucosa in the inferior meatus was slightly more sensitive than the middle meatus. Conclusion We have measured the threshold to touch (air jet sensitivity) in nine places in each of 141 nasal cavities and determined that the variability and sensitivity of these measurements among people varies by age and the distance from the nostril. Older subjects were found to have a higher threshold for the sensation of air flow, and the nasal vestibule was found to be more sensitive than the rest of the nasal cavity mucosa with the inferior meatus slightly more sensitive then the middle meatus.

Relationship of eosinophils and plasma cells to biofilm in chronic rhinosinusitis.

Background This study investigates the relationship of eosinophils and plasma cells to biofilm in chronic rhinosinusitis (CRS). A prospective observational study was performed at the Keck Hospital, University of Southern California, Department of Otolaryngology, Los Angeles, CA. Methods A total of 29 patients, 20 undergoing endoscopic sinus surgery for CRS and 9 control patients undergoing septoplasty for nasal obstruction without history or evidence of CRS, were included in this study. Contiguous sinonasal mucosa sample sections were examined by hematoxylin and eosin (H&E), fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC) for biofilm, microbes, eosinophil major basic protein (EMBP), and cluster designation 27 (CD27). EMBP and CD27 were used as eosinophil and plasma cell markers, respectively. Results Biofilm was visualized in 15 of 20 patients with CRS on H&E sections, confirmed by microbial presence using FISH. Biofilm was not identified in tissue samples of the nine control patients. On IHC analysis, CD27 and EMBP expression were significantly higher in patients with CRS compared with control (p < 0.05) and had greater expression in biofilm-positive patients compared with biofilm-negative patients. Nasal polyps correlated with higher expression of CD27 and EMBP, but in CRS patients without polyps CD27 and EMBP was also significantly greater in biofilm-positive specimens compared with biofilm-negative specimens. Conclusion Biofilm presence in CRS appears to correlate to host inflammatory response involving plasma cell and eosinophil recruitment.

Olfactory neuroepithelium-derived neural progenitor cells as a model system for investigating the molecular mechanisms of neuropsychiatric disorders.

Objective Most expression profiling studies of neuropsychiatric disorders have used RNA from postmortem brain tissue. Such studies are confounded by terminal events, environmental variables, such as drug use or abuse, postmortem interval, and tissue pH. To address these limitations, we have explored the use of cultured neuronal cells derived from olfactory neuroepithelium (CNON) from nasal biopsies as an alternate source of RNA. CNON cells are primarily composed of neural progenitor cells and are less influenced by environmental variables as compared with adult postmortem brain tissue. Methods We collected biopsy samples and established CNON cultures from eight schizophrenia cases and eight healthy comparison individuals. RNA from the cells was profiled using Affymetrix Human Exon 1.0 ST arrays and the results were validated by immunostaining and real-time quantitative PCR. Results The expression data show that CNON are primarily composed of neural progenitor cells. Furthermore, we observed a substantially higher correlation of global expression between control samples of CNON (0.98), as compared with postmortem tissue (GDS1917) (0.88). Finally, using the genome-wide expression data, we were able to differentiate CNON samples derived from individuals with and without schizophrenia in a principal component analysis and to identify candidate schizophrenia genes. Conclusion CNON is a novel model system for the study of neuropsychiatric disorders that drastically reduces both technical and biological noise as compared with postmortem tissue and is therefore well suited for the identification of genes that are differentially expressed between cases and controls.

Endoscopic endonasal transsphenoidal surgery: implementation of an operative and perioperative checklist

Endoscopic endonasal surgery relies heavily on specialized operative instrumentation and optimization of endocrinological and other critical adjunctive intraoperative factors. Several studies and worldwide initiatives have previously established that intraoperative and perioperative surgical checklists can minimize the incidence of and prevent adverse events. The aim of this article was to outline some of the most common considerations in the perioperative and intraoperative preparation for endoscopic endonasal transsphenoidal surgery. The authors implemented and prospectively evaluated a customized checklist at their institution in 25 endoscopic endonasal operations for a variety of sellar and skull base pathological entities. Although no major errors were detected, near misses pertaining primarily to missing components of surgical equipment or instruments were identified in 9 cases (36%). The considerations in the checklist provided in this article can serve as a basic template for further customization by centers performing endoscopic endonasal surgery, where their application may reduce the incidence of adverse or preventable errors associated with surgical treatment of sellar and skull base lesions.

Assessing the efficacy of endoscopic office olfactory biopsy sites to produce neural progenitor cell cultures for the study of neuropsychiatric disorders

The olfactory region is capable of continuous neurogenesis. Situated on the cribriform plate and segments of the superior septum and both superior and middle turbinates, it is accessible through office‐based biopsy and can be used to generate neural progenitor cells to study molecular abnormalities associated with neuropsychiatric disorders. The purpose of the study was to evaluate the efficacy of the endoscopic office olfactory biopsy from middle turbinate and superior‐posterior septum to produce the neural progenitor cells.

Perfusion-based human cadaveric specimen as a simulation training model in repairing cerebrospinal fluid leaks during endoscopic endonasal skull base surgery

OBJECTIVE Competency in endoscopic endonasal approaches (EEAs) to repair high-flow cerebrospinal fluid (CSF) leaks is an essential component of the neurosurgical training process. The objective of this study was to demonstrate the feasibility of a simulation model for EEA repair of anterior skull base CSF leaks. METHODS Human cadaveric specimens were utilized with a perfusion system to simulate a high-flow CSF leak. Neurological surgery residents (postgraduate year 3 or greater) performed a standard EEA to repair a CSF leak using a combination of fat, fascia lata, and pedicled nasoseptal flaps. A standardized 5-point Likert questionnaire was used to assess the knowledge gained, techniques learned, degree of safety, benefit of CSF perfusion during repair, and pre- and posttraining confidence scores. RESULTS Intrathecal perfusion of fluorescein-infused saline into the ventricular/subarachnoid space was successful in 9 of 9 cases. The addition of CSF reconstitution offered the residents visual feedback for confirmation of intraoperative CSF leak repair. Residents gained new knowledge and a realistic simulation experience by rehearsing the psychomotor skills and techniques required to repair a CSF leak with fat and fascial grafts, as well as to prepare and rotate vascularized nasoseptal flaps. All trainees reported feeling safer with the procedure in a clinical setting and higher average posttraining confidence scores (pretraining 2.22 ± 0.83, posttraining 4.22 ± 0.44, p < 0.001). CONCLUSIONS Perfusion-based human cadaveric models can be utilized as a simulation training model for repairing CSF leaks during EEA.

Gene expression in patient-derived neural progenitors provide insights into neurodevelopmental aspects of schizophrenia

The PGC2 schizophrenia (SCZ) GWAS shows that variation in non-coding regions is responsible for most of the common variation heritability of the disease, suggesting risk variants alter gene expression. Therefore, comparing differences in gene expression between cases and controls may provide a direct approach for studying the etiology of SCZ. We studied transcriptome expression profiles of Cultured Neural progenitor cells derived from Olfactory Neuroepithelium lines (CNON) from 144 SCZ and 111 control individuals using RNA-Seq and identified 53 differentially expressed (DEX) genes (FDRBACKGROUND GWAS of schizophrenia demonstrated that variations in the non-coding regions are responsible for most of common variation heritability of the disease. It is hypothesized that these risk variants alter gene expression. Thus, studying alterations in gene expression in schizophrenia may provide a direct approach to understanding the etiology of the disease. In this study we use Cultured Neural progenitor cells derived from Olfactory Neuroepithelium (CNON) as a genetically unaltered cellular model to elucidate the neurodevelopmental aspects of schizophrenia. METHODS We performed a gene expression study using RNA-Seq of CNON from 111 controls and 144 individuals with schizophrenia. Differentially expressed (DEX) genes were identified with DESeq2, using covariates to correct for sex, age, library batches and one surrogate variable component. RESULTS 80 genes were DEX (FDR<10%), showing enrichment in cell migration, cell adhesion, developmental process, synapse assembly, cell proliferation and related gene ontology categories. Cadherin and Wnt signaling pathways were positive in overrepresentation test, and, in addition, many genes are specifically involved in Wnt5A signaling. The DEX genes were significantly, enriched in the genes overlapping SNPs with genome-wide significant association from the PGC GWAS of schizophrenia (PGC SCZ2). We also found substantial overlap with genes associated with other psychiatric disorders or brain development, enrichment in the same GO categories as genes with mutations de novo in schizophrenia, and studies of iPSC-derived neural progenitor cells. CONCLUSIONS CNON cells are a good model of the neurodevelopmental aspects of schizophrenia and can be used to elucidate the etiology of the disorder.

Extended endoscopic endonasal approach for resection of tuberculum sellae meningioma

Meningiomas are the most prevalent primary intracranial tumor, with 3%-10% arising from the tuberculum sellae. Optimal management consists of total microsurgical resection with preservation of surrounding structures. The authors present a 64-year-old woman with progressive bilateral vision loss, including visual acuity deficits and bitemporal hemianopsia. MRI revealed a 2-cm tuberculum sellae meningioma causing optic apparatus compression. An extended endoscopic endonasal transtuberculum approach was utilized for gross-total resection, including microdissection of tumor from the optic chiasm and infundibulum. Closure was performed with multilayer tensor fascia lata autograft and a pedicled nasal-septal flap. The patients postoperative exam showed visual improvement and normal pituitary function. The video can be found here: https://youtu.be/ZfNB_rhlyeI .

Determinants and Evaluation of Nasal Airflow Perception

Abstract The sensation of nasal airflow, or nasal airway patency, is an important consideration in the treatment outcome of nasal airway obstruction. Clinicians striving to optimize the nasal passageway have relied on techniques aimed at decreasing peak airway resistance across nasal valves. Nonetheless, the evaluation of the nasal airway is multifaceted, and the objective determinants of subjective nasal patency remain incompletely elucidated. While rhinomanometry, peak nasal inspiratory airflow, and acoustic rhinometry have traditionally been used in research to focus on resistance as a measure of patency, an emerging body of evidence suggests that subjective nasal patency is more significantly correlated to the dynamic change of nasal mucosal temperature. The objective of this review is to provide the technical background on nasal airflow perception and intranasal trigeminal function as crucial to those performing functional and aesthetic rhinosurgery.

Resolution of Chronic Aspiration Pneumonitis Following Endoscopic Endonasal Repair of Spontaneous Cerebrospinal Fluid Fistula of the Skull Base

Spontaneous cerebrospinal fluid (CSF) rhinorrhea due to a skull base defect requires prompt diagnosis and treatment. Multiple surgical options are available for repairing the fistula, including the two-layer “fascial apposition” method and use of a pedicled nasal-septal flap. A 44-year-old obese woman presented with 4 months of progressive cough, exertional dyspnea, hoarseness, and intermittent fluid drainage from the right nostril. Chest computed tomography (CT) imaging and bronchoscopy showed chronic pneumonitis, which was confirmed by pulmonary wedge resection. CT and magnetic resonance imaging of the skull base, as well as laboratory analysis of the nasal fluid for β2-transferrin, confirmed a skull base defect causing CSF rhinorrhea. During surgery, insertion of a lumbar drain with the intrathecal fluorescein administration was performed, followed by endoscopic endonasal repair using an autologous fascial apposition graft and pedicled nasal-septal flap. Both the CSF leak and the pulmonary complications resolved following the operation with no symptoms at 11-month follow-up. This is the first reported case of spontaneous CSF rhinorrhea complicated by chronic aspiration and pneumonitis. Increased diagnostic complexity due to chronic pulmonary complications resulted in unnecessary interventions and treatment delays. Prompt recognition of spontaneous CSF leaks is essential to prevent potentially harmful complications.