Divergent bitter and sweet taste perception intensity in chronic rhinosinusitis patients.

BACKGROUND: Bitter and sweet taste receptors are present in the human upper airway, where they have roles in innate immunity. Previous studies have shown that 1 of the 25 bitter receptors, TAS2R38, responds to specific bacterial signaling molecules and evokes 1 type of a defense response in the upper airway, whereas ligands of sweet receptors suppress other types of defense responses. METHODS: We examined whether other bitter taste receptors might also be involved in innate immunity by using sensory responses to bitter compounds that are not ligands of TAS2R38 (quinine and denatonium benzoate) to assess the sensitivity of other bitter receptors in chronic rhinosinusitis (CRS) patients. CRS patients with (n = 426) and without (n = 226) nasal polyps and controls (n = 356) rated the intensity of quinine, denatonium benzoate, phenylthiocarbamide (PTC; a ligand for TAS2R38), sucrose, and salt. RESULTS: CRS patients rated the bitter compounds denatonium benzoate and quinine as less intense and sucrose as more intense than did controls (false discovery rate [FDR] <0.05) and CRS patients and controls did not differ in their ratings of salt (FDR >0.05). PTC bitter taste intensity differed between patient and control groups but were less marked than those previously reported. Though differences were statistically significant, overall effect sizes were small. CONCLUSION: CRS patients report bitter stimuli as less intense but sweet stimuli as more intense than do control subjects. We speculate that taste responses may reflect the competence of sinonasal innate immunity mediated by taste receptor function, and thus a taste test may have potential for clinical utility in CRS patients.

Preoperative Lund-Mackay computed tomography score is associated with preoperative symptom severity and predicts quality-of-life outcome trajectories after sinus surgery.

BACKGROUND: Disagreement exists about the relationship between Lund-Mackay CT scores (LMCTS) and quality-of-life outcome (QoL) measures. We investigated whether preoperative LMCTS are associated with preoperative QoL, and whether LMCTS is predictive of postoperative QoL outcomes in chronic rhinosinusitis (CRS) patients. METHODS: Adult patients with medically recalcitrant CRS (n = 665) were enrolled in a prospective, observational cohort study. Preoperative LMCTS and pre- and postoperative self-reported QoL outcomes (22-item Sino-Nasal Outcomes Test [SNOT-22]) were collected and evaluated over 12 months. Five hundred sixty-eight patients met the inclusion criteria. Longitudinal linear mixed-effects modeling was used to investigate the effect of LMCTS on QoL after functional endoscopic sinus surgery (FESS). RESULTS: Preoperative LMCTS were significantly associated with preoperative SNOT-22 scores (p < 0.01) and postoperative SNOT-22 scores (p < 0.001), driven by Extranasal and Rhinologic subdomains of the QoL questionaire. Patients in the lowest preoperative LMCTS quartile had the lowest mean change in SNOT-22 scores at 12 months (16.8 points; 95% confidence interval [CI], 12.2-21.3). Patients in the second and third lowest preoperative LMCTS quartiles had mean changes at 12 months of 21.1 points (95% CI, 16.7-25.4) and 23.1 points (95% CI, 18.3-27.9). Patients in the highest preoperative LMCTS quartile had the greatest improvement in SNOT-22 scores after FESS (29.9 points; 95% CI, 24.9-34.8). The difference in QoL change at 12 months between the highest and lowest preoperative LMCTS quartiles was 13.1 points (95% CI, 6.0-20.2; p < 0.001). CONCLUSION: Our study demonstrates that preoperative LMCTS correlate with preoperative extranasal and rhinologic symptom severity and that the LMCTS is an indicator of postsurgical QoL outcomes for medically recalcitrant chronic rhinosinusitis patients in a large tertiary otolaryngology setting.

Outcomes after complete endoscopic sinus surgery and aspirin desensitization in aspirin-exacerbated respiratory disease.

BACKGROUND: In this study we assessed patient outcomes after complete endoscopic sinus surgery (ESS) and aspirin desensitization for patients with aspirin-exacerbated respiratory disease (AERD). METHODS: A retrospective chart review was conducted for patients with aspirin challenge-proven AERD who underwent complete ESS followed by aspirin desensitization. Outcomes assessed included need for revision surgery and quality-of-life measures using the 22-item Sino-Nasal Outcomes Test (SNOT-22). Data were collected preoperatively, postoperatively prior to desensitization, and then at intervals post-desensitization through 30 months after aspirin desensitization. A longitudinal linear mixed-effects model was used for data analysis. RESULTS: Thirty-four patients met the inclusion criteria for this study. Thirty-two patients successfully completed aspirin desensitization and were subsequently followed for 30 months after desensitization. Two patients were unable to complete desensitization. Five patients discontinued aspirin maintenance therapy due to gastrointestinal and respiratory side effects. Within the follow-up period, there were only 3 (9.4%) revision sinus surgeries. Notably, 1 of these revision cases occurred in a patient who had discontinued aspirin maintenance therapy. After surgical treatment and prior to desensitization patients had significant reductions in SNOT-22 scores. Our results demonstrate that total SNOT-22 scores remained statistically unchanged from immediate post-desensitization throughout the 30-month follow-up period. CONCLUSION: Complete sinus surgery followed by timely aspirin desensitization and maintenance therapy is an effective combination in the long-term management of sinus disease in patients with AERD.

Make it two: A case report of dual sequential external defibrillation.

ABSTRACTDual sequential external defibrillation (DSED) is the process of near simultaneous discharge of two defibrillators with differing pad placement to terminate refractory arrhythmias. Previously used in the electrophysiology suite, this technique has recently been used in the emergency department and prehospital setting for out-of-hospital cardiac arrest (OHCA). We present a case of successful DSED in the emergency department with neurologically intact survival to hospital discharge after refractory ventricular fibrillation (RVF) and review the putative mechanisms of action of this technique.

Denatonium-induced sinonasal bacterial killing may play a role in chronic rhinosinusitis outcomes.

BACKGROUND: Sinonasal bitter taste receptors (T2Rs) contribute to upper airway innate immunity and correlate with chronic rhinosinusitis (CRS) clinical outcomes. A subset of T2Rs expressed on sinonasal solitary chemosensory cells (SCCs) are activated by denatonium, resulting in a calcium-mediated secretion of bactericidal antimicrobial peptides (AMPs) in neighboring ciliated epithelial cells. We hypothesized that there is patient variability in the amount of bacterial killing induced by different concentrations of denatonium and that the differences correlate with CRS clinical outcomes. METHODS: Bacterial growth inhibition was quantified after mixing bacteria with airway surface liquid (ASL) collected from denatonium-stimulated sinonasal air-liquid interface (ALI) cultures. Patient ASL bacterial killing at 0.1 mM denatonium and baseline characteristics and sinus surgery outcomes were compared between these populations. RESULTS: There is variability in the degree of denatonium-induced bacterial killing between patients. In CRS with nasal polyps (CRSwNP), patients with increased bacterial killing after stimulation with low levels of denatonium undergo significantly more functional endoscopic sinus surgeries (FESSs) (p = 0.037) and have worse 6-month post-FESS 22-item Sino-Nasal Outcome Test (SNOT-22) scores (p = 0.012). CONCLUSION: Bacterial killing after stimulation with low levels of denatonium correlates with number of prior FESS and postoperative SNOT-22 scores in CRSwNP. Some symptoms of CRS in patients with hyperresponsiveness to low levels of denatonium may be due to increased airway immune activity or inherent disease severity.

Temporal patterns of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography sinonasal uptake after treatment of sinonasal malignancy.

BACKGROUND: Current guidelines have identified 10 to 12 weeks posttreatment as the ideal time-point for improved diagnostic accuracy of positron emission tomography/computed tomography (PET/CT) for deep tissue sites of the head and neck. After treatment, the sinonasal skull base is predisposed to prolonged inflammation that may render this time-point inappropriate for initial posttreatment imaging surveillance for sinonasal malignancies. The purpose of this study is to evaluate temporal trends in 18 F-fluorodeoxyglucose (18 FDG) sinonasal uptake after treatment for sinonasal malignancies to better elucidate the optimal time-point for initial PET/CT posttreatment evaluation in this patient population. METHODS: A retrospective analysis of all successfully treated and non-locally recurrent sinonasal malignancies over a 15-year study period (2000 to 2015) was performed at our institution. Posttreatment 18 FDG PET/CT standardized uptake value data were collected and compared between various time-points (2 to 4 months, 5 to 12 months, 5 to 24 months, and 13 to 24 months) using an independent-samples t test. RESULTS: A statistically significant difference was noted between the posttreatment time windows 2 to 4 and 5 to 12 months (p = 0.048) as well as 2 to 4 and 5 to 24 months (p = 0.02). A trend toward significance was seen when comparing 2 to 4 and 13 to 24 months (p = 0.083). CONCLUSION: Our analysis of PET/CT in patients previously treated for sinonasal malignancy suggests that the posttreatment sinonasal skull base is characterized by a prolonged period of hypermetabolism that endures beyond the period previously described for deep tissue sites of the head and neck. These findings prompt a reevaluation of the previously described 10- to 12-week cutoff point for initial posttreatment PET/CT for head and neck squamous cell carcinoma as applied to sinonasal malignancies.

T2R38 genotype is correlated with sinonasal quality of life in homozygous ΔF508 cystic fibrosis patients.

BACKGROUND: Chronic rhinosinusitis (CRS) is very prevalent in the cystic fibrosis (CF) patient population, and leads to high morbidity and markedly decreased quality of life (QOL). Identification of genetic markers that contribute to CRS symptoms in these patients can allow for risk stratification and tailoring of medical and surgical treatments. T2R38 is a bitter taste receptor expressed in the sinonasal tract, and nonfunctional alleles of this receptor have been implicated in treatment-refractory CRS in non-CF patients. The purpose of this study is to investigate the significance of T2R38 genotype in the variability of sinonasal QOL and CRS disease severity in a sample of CF patients. METHODS: ΔF508 homozygous CF patients were recruited from the University of Pennsylvania Cystic Fibrosis Center and were genotyped for the TAS2R38 locus. To assess sinonasal symptom severity, a 22-item Sino-Nasal Outcome Test (SNOT-22) was collected from each patient. Additional demographic and medical history data was obtained at the time of patient enrollment. RESULTS: A total of 49 ΔF508 homozygous CF patients aged 18 to 32 years were included in the final SNOT-22 score analysis. Individuals with 2 functional T2R38 alleles (PAV/PAV) had significantly lower SNOT-22 scores (n = 49, p < 0.05). On further breakdown of SNOT-22 subcategories, rhinologic symptoms specifically were less severe in PAV/PAV patients than patients with other genotypes (n = 47, p < 0.05). CONCLUSION: Our investigation indicates that T2R38 genotype correlates both with SNOT-22 scores and rhinologic-specific QOL in ΔF508 homozygous CF patients.

Efeitos da anisometropia induzida experimentalmente na binocularidade de crianças portadoras de leve ambliopia / The effect of experimentally induced anisometropia on binocularity in mildly amblyopic children

Objetivo: O objetivo desse estudo foi analizar os efeitos da anisotropia na visäo binocular em crianças normais e portadoras de discreta ambliopia. Métodos: 20 pacientes com idade entre 6 e 12 anos foram estudados. Todos tinham pelo menos 40 segundos de arco de estereopsia. 10 pacientes tinham acuidade visual normal (controle), e 10 tinham leve ambliopia monocular.A interaçäo binocular foi medida pelo estereoteste de Titmos e o teste de Worth 4 pontos de luz - W4D. Miopia, hipermetropia e astigmatismo a 90º e 45º (variando de 1 a 4 graus) foram introduzidos unilateralmente em cada indivíduo usando armaçäo de prova. Resultados: Todos os indivíduos, independente do grupo, demonstraram uma diminuiçäo na funçäo binocular com o aumento dos níveis de anisometria. Isto foi detectado pelo aumento da área de supressäo no teste de W4D e no decréscimo da estereoacuidade no teste de Titmus. Näo houve diferença dos valores medianos da estereopsia entre os grupos em nenhum nível de anisometria. Conclusäo: Pequenos graus de anisometria podem causar significantes alteraçöes na funçäo binocular em crianças. Leve ambliopia monocular parece näo afetar significativamente essa relaçäo.