Cultured Mesenchymal Cells from Nasal Turbinate as a Cellular Model of the Neurodevelopmental Component of Schizophrenia Etiology.

The study of neurodevelopmental molecular mechanisms in schizophrenia requires the development of adequate biological models such as patient-derived cells and their derivatives. We previously utilized cell lines with neural progenitor properties (CNON) derived from the superior or middle turbinates of patients with schizophrenia and control groups to study schizophrenia-specific gene expression. In this study, we analyzed single-cell RNA seq data from two CNON cell lines (one derived from an individual with schizophrenia (SCZ) and the other from a control group) and two biopsy samples from the middle turbinate (MT) (also from an individual with SCZ and a control). We compared our data with previously published data regarding the olfactory neuroepithelium and demonstrated that CNON originated from a single cell type present both in middle turbinate and the olfactory neuroepithelium and expressed in multiple markers of mesenchymal cells. To define the relatedness of CNON to the developing human brain, we also compared CNON datasets with scRNA-seq data derived from an embryonic brain and found that the expression profile of the CNON closely matched the expression profile one of the cell types in the embryonic brain. Finally, we evaluated the differences between SCZ and control samples to assess the utility and potential benefits of using CNON single-cell RNA seq to study the etiology of schizophrenia.

Intravascular Large B-cell Lymphoma Diagnosed by Nasal Biopsy in a Patient Presenting with Bilateral Ptosis and Ophthalmoplegia.

Intravascular large B-cell lymphoma (IVLBCL) is a rare type of lymphoma, involving the lumen of predominantly small blood vessels, especially capillaries. The orbit is an uncommon site of involvement for IVLBCL, and diagnosis before autopsy is even more rare as most cases are established post-mortem. Herein, the authors describe a 73-year-old male who presented with 3 weeks of progressive bilateral ptosis and ophthalmoplegia. Computed tomography (CT) and subsequent magnetic resonance imaging (MRI) revealed diffuse abnormal thickening and enhancement of bilateral orbital apices, superior orbital fissures, and cavernous sinus, along with persistent focal opacification of the left frontal and ethmoid sinuses. Infectious and inflammatory workup of serum and cerebrospinal fluid was negative. Ethmoidal sinus and middle turbinate biopsy confirmed intravascular large B-cell lymphoma and the patient was started on R-CHOP chemotherapy regimen.

Cell Type Catalog of Middle Turbinate Epithelium (Cell Catalog of Turbinate Epithelium).

Objective: Single-cell RNA-sequencing of middle turbinate mucosa was performed to create the first single-cell transcriptome catalog of this part of the human body. Study Design: Basic science research. Setting: Single center, tertiary care center. Methods: Samples were obtained from the head of the middle turbinate from a healthy volunteer. After the specimen was prepared per lab protocol, cells were dissociated, resuspended, and counted. Single-cell libraries were then prepared according to the 10x Genomics protocol and sequenced using NovaSeq 6000 (Illumina). Sequencing data were processed using Cell Ranger, and clustering and gene expression analysis was performed using Seurat. Cell types were annotated through expression profiling of single cells using known markers and data from other single-cell studies. Results: Fourteen unique cell types were identified, including serous, goblet, club, basal, ciliated, endothelial, and mesenchymal cells, as well as multiple types of blood cells. Conclusion: This catalog provides a comprehensive depiction of the cellular composition of middle turbinate mucosa. By uncovering the cellular stratification of gene expression profiles in the healthy middle turbinate epithelium, the groundwork has been laid for further investigation into the molecular pathogenesis and targeted therapy of sinonasal disease.

Cultured Mesenchymal Cells from Nasal Turbinate as a Cellular Model of the Neurodevelopmental Component of Schizophrenia Etiology.

Study of the neurodevelopmental molecular mechanisms of schizophrenia requires the development of adequate biological models such as patient-derived cells and their derivatives. We previously used cell lines with neural progenitor properties (CNON) derived from superior or middle turbinates of patients with schizophrenia and control groups to study gene expression specific to schizophrenia. In this study, we compared single cell-RNA seq data from two CNON cell lines, one derived from an individual with schizophrenia (SCZ) and the other from a control group, with two biopsy samples from the middle turbinate (MT), also from an individual with SCZ and a control. In addition, we compared our data with previously published data from olfactory neuroepithelium (1). Our data demonstrated that CNON originated from a single cell type which is present both in middle turbinate and olfactory neuroepithelium. CNON express multiple markers of mesenchymal cells. In order to define relatedness of CNON to the developing human brain, we also compared CNON datasets with scRNA-seq data of embryonic brain (2) and found that the expression profile of CNON very closely matched one of the cell types in the embryonic brain. Finally, we evaluated differences between SCZ and control samples to assess usability and potential benefits of using single cell RNA-seq of CNON to study etiology of schizophrenia.

Elevated levels of calpain 14 in nasal tissue in chronic rhinosinusitis.

Sinusitis is a common condition associated with inflammation in the sinuses and nasal mucosa. Calpain 14 is highly expressed in the nasal tissues of sinusitis subjects. Calpain 14 is associated with epithelial barrier disruption. https://bit.ly/3fyAwVO.

Elevated S100A9 expression in chronic rhinosinusitis coincides with elevated MMP production and proliferation in vitro.

Chronic rhinosinusitis (CRS) is a common condition associated with inflammation and tissue remodeling of the nose and paranasal sinuses, frequently occurring with nasal polyps and allergies. Here we investigate inflammation and the protease profile in nasal tissues and plasma from control non-CRS patients and CRS patients. Gene expression for several cytokines, proteases, and antiproteases was quantified in nasal tissue from non-CRS and CRS subjects with nasal polyps. Elevated expression of S100A9, IL1A, MMP3, MMP7, MMP11, MMP25, MMP28, and CTSK was observed in tissue from CRS subjects with nasal polyps compared to control tissue. Tissue protein analysis confirmed elevated levels of these targets compared to controls, and increased MMP3 and MMP7 observed in CRS subjects with nasal polyps compared to CRS subjects without polyps. Plasma concentrations of MMP3 and MMP7 were elevated in the CRS groups compared to controls. The nasal cell line, CCL-30, was exposed to S100A9 protein, resulting in increased MMP3, MMP7, and CTSK gene expression and elevated proliferation. Silencing MMP3 significantly reduced S100A9-mediated cell proliferation. Therefore, the elevated expression of S100A9 and MMPs are observed in CRS nasal tissue and S100A9 stimulated MMP3 responses to contribute to elevated nasal cell proliferation.

Practice Patterns of Systemic Corticosteroid Use in Complicated Acute Rhinosinusitis Among Rhinologists and Pediatric Otolaryngologist.

BACKGROUND: The use of systemic corticosteroids remains controversial in the treatment of orbital complications of sinusitis. OBJECTIVE: To compare and contrast the current practice patterns of the use of systemic corticosteroid in the management of orbital complications of acute bacterial rhinosinusitis (ABRS) among fellowship-trained members of American Society of Pediatric Otolaryngology (ASPO) and American Rhinologic Society (ARS). STUDY DESIGN: Cross-sectional survey. METHODS: A web-based survey was electronically distributed to 497 members of ASPO and 845 members of ARS focusing on the practice habits and opinions regarding the use of systemic corticosteroids in the treatment of ABRS with orbital complications in children and adults. RESULTS: Survey completion rate was 19.1% among ASPO membership and 10.3% from ARS; 45% of respondents utilized steroids almost always or frequently in children and 36% of the time in adults. Most commonly reported indication for the use of steroid was vision change. Fellowship-trained pediatric otolaryngologists are 2.88 times more likely to prescribe corticosteroids for children than rhinologists ( P < .02). The perceived level of evidence in the literature was split between expert opinions and cohort studies. CONCLUSION: In orbital complications of ABRS, practice patterns of the use of steroid differ significantly between fellowship-trained ASPO and ARS members with respect to its use in children. Overall, corticosteroids are administered with significant frequency, although there is little actual or perceived evidence to support their safety or efficacy. In alignment of practicing evidence-based medicine, further studies are needed to guide the use of steroids in complicated ABRS with respect to timing, dosing, route, duration, and indication.

Endoscopic Sinus Surgery Improves Sleep Quality in Chronic Rhinosinusitis: A Systematic Review and Meta-analysis.

Objective Up to 75% of patients with chronic rhinosinusitis (CRS) suffer with poor sleep quality and reduced quality of life. Endoscopic sinus surgery has demonstrated encouraging results in improving sleep function. The aim of this systematic review is to assess the change in sleep quality after surgery for CRS. Data Sources PubMed, Web of Science, EMBASE. Review Methods An electronic search was conducted with the keywords "sinusitis" or "rhinosinusitis" and "sleep." Studies were included only when adults underwent endoscopic sinus surgery and were evaluated pre- and postoperatively by the Epworth Sleepiness Scale (ESS), the Pittsburgh Sleep Quality Index (PSQI), the Apnea-Hypopnea Index (AHI), the sleep domain of Sino-Nasal Outcome Test-22, or the sleep domain of Rhinosinusitis Disability Index. Results The database search yielded 1939 studies, of which 7 remained after dual-investigator screening. The standardized mean differences (95% CI) for the ESS, PSQI, and AHI were -0.94 (-1.63 to -0.26), -0.80 (-1.46 to -0.14), and -0.20 (-0.32 to -0.07), indicating large, moderate to large, and small improvements, respectively. All analyses displayed high heterogeneity ( I2 = 95%-99%). Conclusion Sleep quality, as measured by the ESS and PSQI surveys, shows substantial improvement after surgery for CRS, with smaller improvement seen for AHI. Generalizability of our results is limited by high heterogeneity among studies and by broad confidence intervals that cannot exclude small to trivial changes. The findings of this meta-analysis provide insight into the effect of CRS-related endoscopic sinus surgery on sleep quality, which should guide future research direction and counseling of patients in the clinical setting.

Caregiver well-being and child quality of life.

OBJECTIVE: To describe the impact of otitis media on the child's family and caregiver, and how this impact influences the caregiver's perception of child's quality of life (QOL) and functional health status (FHS). STUDY DESIGN AND SETTING: Prospective study of children aged 6 months to 12 years with recurrent or chronic otitis media recruited from a primary care pediatrics practice and a referral-based pediatric otolaryngology practice. Survey measures were assessed for test-retest reliability, internal consistency, and validity. Multiple regression analysis was used to explore relationships. RESULTS: We enrolled 159 families, with mean age of 3.3 years for the child and 34 years for the caregiver. Most caregivers attended college (80%) and 64% were employed. The Caregiver Impact Questionnaire (CIQ) had good test-retest reliability (r=0.83), internal consistency (alpha=0.88), and construct validity (r=0.37 to 0.62). Most caregivers (52%) were nervous or agitated at least "some of the time" because of their child's ear problems, 29% lost sleep "a good bit of time," and 56% had to change daily activities. Multivariate analysis showed that caregiver QOL explained 62% of variability in child disease-specific QOL, and that caregiver FHS explained up to 45% of the variability in child FHS. CONCLUSION: The 6-item CIQ survey permits a valid and reliable assessment of otitis media impact on caregivers and family functioning. Caregiver ratings of child QOL and FHS are largely influenced by caregiver perceptions of their own personal situation. SIGNIFICANCE: The caregiver QOL and FHS should be considered when using proxy-completed surveys to assess the impact of otitis media on children.

Human botfly infestation presenting as peri-auricular mass.

To report a new cause of peri-auricular mass in children: cutaneous myiasis-botfly infestation. Case report. The human botfly (Dermatobia hominis) is found in the tropics of Central and South America. However, cases of infestation are uncommon in the United States. We present the case of a 5-year-old girl with cutaneous myiasis in order to expand the differential diagnosis for a peri-auricular mass in children. In our report, the parasite was initially identified as sparganum, but was later reclassified by the center for disease control and prevention (CDC) as a botfly larva. Parasitic infection should be considered with a newly noted head and neck mass, and cutaneous myiasis should be included in the differential diagnosis. Cutaneous myiasis has not been previously reported in the literature describing the peri-auricular region as the site of occurrence. Furthermore, when an unusual parasite is extracted from a lesion, it should be confirmed by an authority such as CDC for definitive diagnosis, so appropriate plan of care and follow up can be instituted.

Age as a prognostic factor for complications of major head and neck surgery.

OBJECTIVE: To determine if age alone is a prognostic indicator of surgical outcomes for major head and neck procedures. DESIGN: Retrospective cohort study over a 4-year period. SETTING: Academic referral center, institutional practice, hospitalized care. PATIENTS: Included in this study were patients who had undergone ablative, reconstructive, and other major surgical procedures of the head and neck, including neck dissection, laryngectomy, maxillectomy, thyroidectomy with lymphadenectomy, and composite resection of the oral cavity with reconstruction, for both malignant and benign disease. MAIN OUTCOME MEASURES: Patient data and intraoperative and postoperative course factors were recorded. Comorbidity was graded using an Adult Comorbidity Evaluation 27 test, Charlson Comorbidity Index, and American Society of Anesthesiology score. Postoperative complications were dichotomized, and multiple logistic regression was used for data analysis. RESULTS: Medical chart review identified 157 cases. Analysis of data revealed that time under general anesthesia was the only factor consistently related to complications (P<.006), and it was the only factor consistently related to length of stay (P<.001). Analysis of major complications (6% incidence) as an outcome using univariate analysis resulted in a strong positive correlation with both comorbidity indexes: Adult Comorbidity Evaluation 27 (P = .002) and Charlson Comorbidity Index (P = .005). Multiple logistic regression showed no significant relationship between age 70 years or older (20% of patients) and either complications or hospital length of stay. CONCLUSIONS: Patient's age alone is not a prognostic indicator of surgical outcome for major head and neck procedures. However, comorbidity is an important predictive factor for postoperative complications in any age group. Time under general anesthesia showed a statistically significant relationship with complication rate and hospital length of stay in multivariate analyses. Consequently, prevention of complications should focus on optimizing preoperative comorbid conditions.

Evidence-based medicine in otolaryngology journals.

OBJECTIVE: We set out to assess, within the context of evidence-based medicine, the levels of supporting evidence for therapeutic recommendations made in leading otolaryngology journals. DESIGN: We used a cross-sectional survey of clinical research articles published in 1999 in 4 high-circulation otolaryngology journals. OUTCOME MEASURES: We used study design methodology and level of evidence for clinical research articles with therapeutic recommendations. Outcomes were stratified by type of recommendation (positive vs negative) and by study focus (medical vs surgical therapy). RESULTS: Of the 1019 articles identified, 737 (72%) were clinical research and 268 (36%) made therapeutic recommendations. Median sample size was modest (27 subjects), with only 38% of studies reflecting planned research and 22% including an internal control or comparison group. Positive studies were 20 times more prevalent than negative ones, but were 69% less likely to have an internal control group (P =.042) and 93% less likely to include confidence intervals (P =.020). Moreover, the level of evidence for positive studies was lower than for negative studies (P =.037), with twice as many negative recommendations supported by analytic research. Similarly, the level of evidence for operation was lower than for medical therapy (P <.001), with 3 times as many medical recommendations supported by analytic research. CONCLUSIONS: Most therapeutic recommendations in otolaryngology journals are on the basis of descriptive case series (80%) and least often on randomized controlled trials (7%). A dual standard appears to exist for negative versus positive studies and for medical versus surgical recommendations. Greater scrutiny of the breadth and quality of evidence levels supporting therapeutic recommendations is likely to occur as the popularity of-and demand for-evidence-based medicine increases. SIGNIFICANCE: Evaluation of levels of evidence in otolaryngology decision making.

Electronic medical records for otolaryngology office-based practice.

PURPOSE OF REVIEW: Pressure is mounting on physicians to adopt electronic medical records. The field of health information technology is evolving rapidly with innovations and policies often outpacing science. We sought to review research and discussions about electronic medical records from the past year to keep abreast of these changes. RECENT FINDINGS: Original scientific research, especially from otolaryngologists, is lacking in this field. Adoption rates are slowly increasing, but more of the burden is shouldered by physicians despite policy efforts and the clear benefits to third-party payers. Scientific research from the past year suggests lack of improvements and even decreasing quality of healthcare with electronic medical record adoption in the ambulatory care setting. The increasing prevalence and standardization of electronic medical record systems results in a new set of problems including rising costs, audits, difficulties in transition and public concerns about security of information. SUMMARY: As major players in healthcare continue to push for adoption, increased effort must be made to demonstrate actual improvements in patient care in the ambulatory care setting. More scientific studies are needed to demonstrate what features of electronic medical records actually improve patient care. Otolaryngologists should help each other by disseminating research about improvement in patient outcomes with their systems since current adoption and outcomes policies do not apply to specialists.