The association of active and passive tobacco smoke exposure with chronic rhinosinusitis symptom severity: A cross-sectional study.

BACKGROUND: Chronic rhinosinusitis (CRS) causes a great deal of morbidity. There are a multitude of causal factors, though their precise contribution to symptom severity has yet to be defined.  We hypothesized that exposure to both primary and secondhand tobacco smoke would correlate with more severe symptoms of CRS. METHODS: This is a prospective cross-sectional study performed at an academic tertiary care medical center from 2010 to 2013. A total of 85 consecutive patients with chronic sinusitis were screened; 70 with medically refractory CRS requiring functional Endoscopic sinus surgery (FESS) were enrolled. Recent tobacco exposure was assessed using serum cotinine levels. Sinonasal mucosa was biopsied to assess ciliary architecture. Demographics, medical history, tobacco and environmental exposures, and computed tomography (CT) imaging were also collected. Two quality of life (QOL) surveys were administered: one disease specific, Sinonasal Outcomes Test-20 (SNOT-20), and one general, Short Form-12 (SF-12). Results were correlated with the aforementioned exposures. RESULTS: The 70 patients had an average age of 46 years, and 42% were male.  Variables that correlated with worse SNOT-20 scores included serum cotinine (r = 0.43, p = 0.002), number of cigarettes smoked daily (r = 0.27, p = 0.03), and number of secondhand cigarettes exposed to per day (r = 0.29, p = 0.04). There were no significant correlations between SNOT-20 scores and Lund-MacKay or axonemal ultrastructural abnormalities (AUA)-ciliary scores. The two five-variable models best predicted disease-specific QOL. CONCLUSIONS: Increased amounts of serum cotinine and primary and secondhand smoke exposure were associated with worse sinonasal QOL. This study establishes an objective relationship between smoke exposure and patient-perceived severity of CRS, emphasizing the importance of tobacco cessation counseling as part of management.

Survival outcomes of lateral skull base tumors following temporal bone resection.

BACKGROUND: Lateral skull base tumors often necessitate temporal bone resection (TBR), although clinical outcomes can be unfavorable. Factors influencing survival and recurrence after TBR for cutaneous and salivary malignancies were evaluated. METHODS: Twenty-six TBR subjects were included. Survival and recurrence outcomes were estimated at 1, 2, and 5 years postresection. Prognostic factors were analyzed using univariate and multivariate Cox regression. RESULTS: Two years postresection, the overall survival (OS), disease-specific survival (DSS) and recurrence-free survival (RFS) rates were 61%, 74%, and 49%, respectively, and 51%, 63%, and 45% at 5 years. On univariate analysis, preoperative facial nerve dysfunction and intraoperative nerve sacrifice worsened OS, DSS, and RFS. Prior surgery and adjuvant radiation independently predicted reduced OS, DSS, and RFS on multivariate analysis. CONCLUSIONS: Mortality is highest in the first 2 years following resection. Preoperative facial nerve dysfunction, facial nerve sacrifice, and prior radiation are negative predictors of survival and recurrence.

Association of pulse synchronous tinnitus and sigmoid sinus wall abnormalities in patients with idiopathic intracranial hypertension.

PURPOSE: Pulse synchronous tinnitus (PT) is common in patients with idiopathic intracranial hypertension (IIH) and in those with sigmoid sinus wall abnormalities (SSWAs). Although patients with SSWAs and IIH share many clinical features, the incidence of SSWAs in patients with IIH and its relationship to PT in this cohort is less well established. The purpose of this study is to assess the incidence of SSWAs in patients with IIH and PT, and to determine if there is an association between SSWAs and PT in this population. MATERIALS AND METHODS: Prospective computed tomography (CT) study of adults with IIH. Subjective PT was correlated with presence or absence of SSWAs on CT. RESULTS: 22 subjects were enrolled and 14 subsequently underwent CT. The incidence of SSWAs was significantly higher in subjects with PT than without (70% vs. 0%, p = 0.02). Mean age, BMI and opening pressures did not differ between those with and without SSWAs or PT. CONCLUSIONS: There is a high incidence of SSWAs in subjects with IIH and PT. These findings support an association between SSWAs and PT, and implicate SSWAs as a possible cause of, or contributing factor to, PT in patients with IIH. Patients with IIH and PT that does not resolve with reducing intracranial pressure should undergo diagnostic CT and consider treatment of a SSWA if present.

Human DnaJB6 Antiamyloid Chaperone Protects Yeast from Polyglutamine Toxicity Separately from Spatial Segregation of Aggregates.

Polyglutamine (polyQ) aggregates are associated with pathology in protein-folding diseases and with toxicity in the yeast Saccharomyces cerevisiae Protection from polyQ toxicity in yeast by human DnaJB6 coincides with sequestration of aggregates. Gathering of misfolded proteins into deposition sites by protein quality control (PQC) factors has led to the view that PQC processes protect cells by spatially segregating toxic aggregates. Whether DnaJB6 depends on this machinery to sequester polyQ aggregates, if this sequestration is needed for DnaJB6 to protect cells, and the identity of the deposition site are unknown. Here, we found DnaJB6-driven deposits share characteristics with perivacuolar insoluble protein deposition sites (IPODs). Binding of DnaJB6 to aggregates was necessary, but not enough, for detoxification. Focal formation required a DnaJB6-Hsp70 interaction and actin, polyQ could be detoxified without sequestration, and segregation of aggregates alone was not protective. Our findings suggest DnaJB6 binds to smaller polyQ aggregates to block their toxicity. Assembly and segregation of detoxified aggregates are driven by an Hsp70- and actin-dependent process. Our findings show sequestration of aggregates is not the primary mechanism by which DnaJB6 suppresses toxicity and raise questions regarding how and when misfolded proteins are detoxified during spatial segregation.