Evidence for a role of metformin in preventing olfactory dysfunction among older adults.

BACKGROUND: Olfactory dysfunction (OD) is increasingly recognized as a hallmark of unhealthy aging and is intimately associated with mortality, but therapies remain elusive. Recognizing the increased prevalence of OD in individuals with diabetes, and the potential anti-aging effects of metformin, we studied the association of metformin use with OD. METHODS: Cross-temporal study of participants from Waves 2 (2010-11) and 3 (2015-16) of the National Social Life, Health, and Aging Project (NSHAP), a nationally representative cohort study of community-dwelling older adults. We included participants with diabetes who had complete data on olfaction and relevant covariates at Wave 2 and were not lost to follow-up at Wave 3. Olfactory identification (OI), the ability to identify the odorant, and olfactory sensitivity (OS), the ability to detect the presence of an odorant, were tested. Weighted multivariable logistic regression was used to study the association between metformin use at Wave 2 (baseline) and odds of having impaired OI/OS at Wave 3, adjusted for age, sex, race/ethnicity, education, smoking, BMI, HbA1c, years since diabetes diagnosis, and insulin use. RESULTS: Among 228 participants with diabetes (mean age=70 years, 53% female, 21% Black), 112 (49%) used metformin at baseline. Relative to nonusers, users had 58% lower odds of impaired OI and 67% lower odds of impaired OS at Wave 3. Among participants with normal baseline OS (N=62), users had 97% lower odds of impaired OS at Wave 3. CONCLUSIONS: Metformin use is associated with lower odds of OD among individuals with diabetes, suggesting a potential protective effect on olfaction. Future work including a larger sample and additional information on metformin use is needed to establish whether these findings are independent of diabetic control.

Interventions for the prevention of persistent post-COVID-19 olfactory dysfunction.

BACKGROUND: Loss of olfactory function is well recognised as a symptom of COVID-19 infection, and the pandemic has resulted in a large number of individuals with abnormalities in their sense of smell. For many, the condition is temporary and resolves within two to four weeks. However, in a significant minority the symptoms persist. At present, it is not known whether early intervention with any form of treatment (such as medication or olfactory training) can promote recovery and prevent persisting olfactory disturbance. This is an update of the 2021 review with four studies added. OBJECTIVES: 1) To evaluate the benefits and harms of any intervention versus no treatment for people with acute olfactory dysfunction due to COVID-19 infection.  2) To keep the evidence up-to-date, using a living systematic review approach.  SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the latest search was 20 October 2021. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in people with COVID-19 related olfactory disturbance, which had been present for less than four weeks. We included any intervention compared to no treatment or placebo.  DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were the presence of normal olfactory function, serious adverse effects and change in sense of smell. Secondary outcomes were the prevalence of parosmia, change in sense of taste, disease-related quality of life and other adverse effects (including nosebleeds/bloody discharge). We used GRADE to assess the certainty of the evidence for each outcome.  MAIN RESULTS: We included five studies with 691 participants. The studies evaluated the following interventions: intranasal corticosteroid sprays, intranasal corticosteroid drops, intranasal hypertonic saline and zinc sulphate.  Intranasal corticosteroid spray compared to no intervention/placebo We included three studies with 288 participants who had olfactory dysfunction for less than four weeks following COVID-19. Presence of normal olfactory function The evidence is very uncertain about the effect of intranasal corticosteroid spray on both self-rated recovery of olfactory function and recovery of olfactory function using psychophysical tests at up to four weeks follow-up (self-rated: risk ratio (RR) 1.19, 95% confidence interval (CI) 0.85 to 1.68; 1 study; 100 participants; psychophysical testing: RR 2.3, 95% CI 1.16 to 4.63; 1 study; 77 participants; very low-certainty evidence).  Change in sense of smell The evidence is also very uncertain about the effect of intranasal corticosteroid spray on self-rated change in the sense of smell (at less than 4 weeks: mean difference (MD) 0.5 points lower, 95% CI 1.38 lower to 0.38 higher; 1 study; 77 participants; at > 4 weeks to 3 months: MD 2.4 points higher, 95% CI 1.32 higher to 3.48 higher; 1 study; 100 participants; very low-certainty evidence, rated on a scale of 1 to 10, higher scores mean better olfactory function). Intranasal corticosteroids may make little or no difference to the change in sense of smell when assessed with psychophysical testing (MD 0.2 points, 95% CI 2.06 points lower to 2.06 points higher; 1 study; 77 participants; low-certainty evidence, 0- to 24-point scale, higher scores mean better olfactory function).  Serious adverse effects The authors of one study reported no adverse effects, but their intention to collect these data was not pre-specified so we are uncertain if these were systematically sought and identified. The remaining two studies did not report on adverse effects.  Intranasal corticosteroid drops compared to no intervention/placebo We included one study with 248 participants who had olfactory dysfunction for ≤ 15 days following COVID-19. Presence of normal olfactory function Intranasal corticosteroid drops may make little or no difference to self-rated recovery at > 4 weeks to 3 months (RR 1.00, 95% CI 0.89 to 1.11; 1 study; 248 participants; low-certainty evidence). No other outcomes were assessed by this study.  Data on the use of hypertonic saline nasal irrigation and the use of zinc sulphate to prevent persistent olfactory dysfunction are included in the full text of the review. AUTHORS' CONCLUSIONS: There is very limited evidence available on the efficacy and harms of treatments for preventing persistent olfactory dysfunction following COVID-19 infection. However, we have identified a number of ongoing trials in this area. As this is a living systematic review we will update the data regularly, as new results become available.

A prospective pilot study of the effects of deep brain stimulation on olfaction and constipation in Parkinson's disease.

BACKGROUND: Previous studies suggest deep brain stimulation of the subthalamic nucleus (STN-DBS) may improve olfaction and constipation in PD, using subjective measures. OBJECTIVE: To utilize objective measures to assess olfaction and constipation in PD following STN-DBS. METHODS: In this prospective pilot study, olfaction (University of Pennsylvania Smell Identification Test [UPSIT]), bowel symptoms (ROME III questionnaires, daily bowel diaries, 100 mm visual analog scales for satisfaction with treatment and bowel habits), and motor manifestations of PD were evaluated before and after STN-DBS. Levodopa equivalent daily dose (LEDD) was calculated. RESULTS: Ten patients (8 men, mean age 67.4 ± 6.0 years) with mean PD duration of 7.5 ± 3.7 years underwent bilateral STN-DBS, with mean follow-up of 3 months for all measures, except 7 months follow-up for bowel diaries. There was improvement in the Unified Parkinson's Disease Rating Scale motor "off" scores (33.7 ± 6.7 before and 16.1 ± 10.8 after, P = 0.001). Mean UPSIT scores (20.0 ± 6.6 versus 17.5 ± 5.7, P = 0.03) worsened from severe to total hyposmia. Seven patients had baseline constipation and completed bowel diaries. There was improvement in number of complete spontaneous bowel motions (CBSM) per week (2.2 ± 1.9 before versus 4.7 ± 2.4 after, P = 0.04), satisfaction with treatment of constipation (44 ± 27 before versus 64 ± 25 after, P = 0.02), and with bowel motions (33 ± 22 before and 48 ± 20 after, P = 0.2). However, laxative use (P = 0.15) and LEDD (P = 0.15) were unchanged. CONCLUSION: Olfaction worsened while symptoms of constipation improved but did not resolve after STN-DBS.

Interventions for the prevention of persistent post-COVID-19 olfactory dysfunction.

BACKGROUND: Loss of olfactory function is well recognised as a cardinal symptom of COVID-19 infection, and the ongoing pandemic has resulted in a large number of affected individuals with abnormalities in their sense of smell. For many, the condition is temporary and resolves within two to four weeks. However, in a significant minority the symptoms persist. At present, it is not known whether early intervention with any form of treatment (such as medication or olfactory training) can promote recovery and prevent persisting olfactory disturbance.  OBJECTIVES: To assess the effects (benefits and harms) of interventions that have been used, or proposed, to prevent persisting olfactory dysfunction due to COVID-19 infection. A secondary objective is to keep the evidence up-to-date, using a living systematic review approach.  SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane COVID-19 Study Register; Cochrane ENT Register; CENTRAL; Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished studies. The date of the search was 16 December 2020. SELECTION CRITERIA: Randomised controlled trials including participants who had symptoms of olfactory disturbance following COVID-19 infection. Individuals who had symptoms for less than four weeks were included in this review. Studies compared any intervention with no treatment or placebo.  DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Our primary outcomes were the presence of normal olfactory function, serious adverse effects and change in sense of smell. Secondary outcomes were the prevalence of parosmia, change in sense of taste, disease-related quality of life and other adverse effects (including nosebleeds/bloody discharge). We used GRADE to assess the certainty of the evidence for each outcome.  MAIN RESULTS: We included one study of 100 participants, which compared an intranasal steroid spray to no intervention. Participants in both groups were also advised to undertake olfactory training for the duration of the trial. Data were identified for only two of the prespecified outcomes for this review, and no data were available for the primary outcome of serious adverse effects. Intranasal corticosteroids compared to no intervention (all using olfactory training) Presence of normal olfactory function after three weeks of treatment was self-assessed by the participants, using a visual analogue scale (range 0 to 10, higher scores = better). A score of 10 represented "completely normal smell sensation". The evidence is very uncertain about the effect of intranasal corticosteroids on self-rated recovery of sense of smell (estimated absolute effect 619 per 1000 compared to 520 per 1000, risk ratio (RR) 1.19, 95% confidence interval (CI) 0.85 to 1.68; 1 study; 100 participants; very low-certainty evidence).  Change in sense of smell was not reported, but the self-rated score for sense of smell was reported at the endpoint of the study with the same visual analogue scale (after three weeks of treatment). The median scores at endpoint were 10 (interquartile range (IQR) 9 to 10) for the group receiving intranasal corticosteroids, and 10 (IQR 5 to 10) for the group receiving no intervention (1 study; 100 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS: There is very limited evidence regarding the efficacy of different interventions at preventing persistent olfactory dysfunction following COVID-19 infection. However, we have identified a small number of additional ongoing studies in this area. As this is a living systematic review, the evidence will be updated regularly to incorporate new data from these, and other relevant studies, as they become available.  For this (first) version of the living review, we identified a single study of intranasal corticosteroids to include in this review, which provided data for only two of our prespecified outcomes. The evidence was of very low certainty, therefore we were unable to determine whether intranasal corticosteroids may have a beneficial or harmful effect.

Olfactory changes after endoscopic sinus surgery for chronic rhinosinusitis: A meta-analysis.

BACKGROUND: Endoscopic sinus surgery (ESS) is an important treatment modality for chronic rhinosinusitis (CRS). However, its effect on olfaction remains controversial. OBJECTIVE OF REVIEW: To assess the olfactory impact of ESS in patients with CRS. TYPE OF REVIEW: A meta-analysis. SEARCH STRATEGY: A systematic literature search in the PubMed, EMBASE and Cochrane Library databases was conducted to identify studies that assessed change in olfaction after ESS in patients with CRS. Search terms were related to paranasal sinus diseases, smell and endoscopy. EVALUATION METHOD: The extracted data included authors, publication year, study type, age, sex, diagnostic criteria, surgical mode, sample size, follow-up time, olfaction measurement tool and outcome. We analysed the olfactory changes as continuous variables. RESULTS: Thirty-five studies including 3164 patients with CRS were eligible for the meta-analysis. Among patients having CRS with nasal polyps, olfactory dysfunction improved, as assessed by the Sniffin' Sticks total score (P = .000), Sniffin' Sticks discrimination score (P = .023), Sniffin' Sticks identification score (P = .005), University of Pennsylvania Smell Identification Test (P = .046) and Visual Analogue Scale (P = .000). However, the threshold score of the Sniffin' Sticks test did not improve significantly (P = .361). Olfactory dysfunction did not improve in patients having CRS without nasal polyps according to the University of Pennsylvania Smell Identification Test (P = .404). In non-classified CRS patients, improvement in olfactory dysfunction was observed according to the University of Pennsylvania Smell Identification Test (P = .000), Visual Analogue Scale (P = .001) and Questionnaire of Olfactory Disorders-Negative Statements (P = .001). However, there were no significant improvements according to the Brief Smell Identification Test (P = .325), Sniffin' Sticks threshold score (P = .160) and Sniffin' Sticks identification score (P = .079). CONCLUSION: Endoscopic sinus surgery may be beneficial for improvement in olfactory conditions in patients with CRS. Further thorough and comprehensive studies need to be conducted.

Inducible and conditional activation of ERK5 MAP kinase rescues mice from cadmium-induced olfactory memory deficits.

Cadmium (Cd) is a heavy metal that is one of the most toxic environmental pollutants throughout the world. We previously reported that Cd exposure impairs olfactory memory in mice. However, the underlying mechanisms for its neurotoxicity for olfactory function are not well understood. Since adult Subventricular zone (SVZ) and Olfactory Bulb (OB) neurogenesis contributes to olfaction, olfactory memory defects caused by Cd may be due to inhibition of neurogenesis. In this study, using bromodeoxyuridine (BrdU) labeling and immunohistochemistry, we found that 0.6 mg/L Cd exposure through drinking water impaired adult SVZ/OB neurogenesis in C57BL/6 mice. To determine if the inhibition of olfactory memory by Cd can be reversed by stimulating adult neurogenesis, we utilized the transgenic caMEK5 mouse strain to conditional stimulate of adult neurogenesis by activating the endogenous ERK5 MAP kinase signaling pathway. This was accomplished by conditionally induced expression of active MEK5 (caMEK5) in adult neural stem/progenitor cells. The caMEK5 mice were exposed to 0.6 mg/L Cd for 38 weeks, and tamoxifen was administered to induce caMEK5 expression and stimulate adult SVZ/OB neurogenesis during Cd exposure. Short-term olfactory memory test and sand-digging based, odor-cued olfactory learning and memory test were conducted after Cd and tamoxifen treatments to examine their effects on olfaction. Here we report that Cd exposure impaired short-term olfactory memory and odor-cued associative learning and memory in mice. Furthermore, the Cd-impaired olfactory memory deficits were rescued by the tamoxifen-induction of caMEK5 expression. This suggests that Cd exposure impairs olfactory function by affecting adult SVZ/OB neurogenesis in mice.

Response to Glucocorticosteroids Predicts Olfactory Outcome After ESS in Chronic Rhinosinusitis.

OBJECTIVES: Olfaction is frequently impaired in chronic rhinosinusitis with nasal polyps (CRSwNP) and often improves after endoscopic sinus surgery (ESS). Data about dynamics of olfactory changes after ESS are lacking, and little information is available concerning whether preoperatively administered glucocorticosteroids predict postoperative olfaction. Therefore, the aim of this study was to examine dynamics of olfaction after ESS in relation to the effect of preoperative administration of glucocorticosteroids in CRSwNP. METHODS: This prospective study included 52 CRSwNP patients (30 men, 22 women, mean age 54 ± 14 years) divided into a control group (n = 31) subjected to ESS without preoperative steroids and a treatment group (n = 21) receiving orally administered glucocorticosteroids preoperatively. Self-ratings of olfaction and olfactory testing using the extended Sniffin' Sticks test battery (threshold, discrimination and identification [TDI] score) were performed. Olfaction was measured preoperatively; after termination of glucocorticosteroid treatment (only treatment group); and 2 weeks, 1 month, and 3 months postoperatively. RESULTS: After glucocorticosteroids, TDI score significantly improved in 57% of patients, and olfactory function remained unchanged in 43%. In addition, improvement in TDI score after steroids and 3 months postoperatively were significantly correlated (r = 0.66, P = 0.01). Patients whose olfaction did not improve after glucocorticosteroids did not benefit from surgery. Regarding postoperative olfactory dynamics, TDI score reached its maximum 1 month postoperatively and decreased again approximately 3 months after surgery. CONCLUSION: Glucocorticosteroids improved olfaction in CRSwNP comparable to surgery. In addition, changes in relation to steroids predicted olfactory outcome postoperatively. Regarding the olfactory dynamics, it could be demonstrated that olfactory function increased 1 month after surgery and decreased 3 months postoperatively. LEVEL OF EVIDENCE: 2 Laryngoscope, 130:1616-1621, 2020.

Preservation of olfaction in anterior midline skull base meningiomas: a comprehensive approach.

BACKGROUND: Olfaction is an undervalued sense in neurosurgery. Attempted surgical resection of anterior cranial fossa meningiomas puts the olfactory pathway at risk. Preservation of olfaction may increase the postoperative quality of life. Objective assessment of olfaction may inform clinical decision-making and influence the selection of operative approaches for surgical resection. METHODS: We reviewed all patients who underwent surgical resection for midline anterior skull base meningiomas from July 1, 2014, through December 31, 2017. Patient demographics, tumor size, operative approach, pre- and postoperative deficits, and Simpson grade were collected and analyzed. Postoperative olfaction was assessed by clinical evaluation as well as objective evaluation using the University of Pennsylvania Smell Identification Test (UPSIT). RESULTS: Twenty-eight patients (10 male, 18 female) were included with an average age of 53.8 years (range 27-80 years). Twenty-six patients underwent craniotomy for resection, while 2 patients had endoscopic approaches. Average tumor volume was 402.1 cm3 (6.6-2507.7 cm3). Preoperatively, five patients (17.8%) presented with olfactory impairment. Objectively, 50% of patients (14/28) consented and completed the UPSIT. The average postoperative UPSIT score was 25.8/40 (9/40-38/40). Two patients not identified on clinical assessment alone demonstrated postoperative olfactory deficit on UPSIT (2/14). CONCLUSION: There are limited published studies evaluating olfaction in patients who undergo skull-based approaches for anterior fossa meningiomas. Our series showed the highest olfaction preservation rate (87.5%) using a comprehensive strategy and multitude of surgical approaches based on the olfactory function and tumor characteristics.

Comparison of Olfactory Function and Quality of Life With Different Surgical Techniques for Nasal Septum Deviation.

OBJECTIVE: To assess the nasal functions, nasal resistance, olfactory function, and quality of life in different surgical techniques for nasal septum deviation STUDY DESIGN:: Randomized controlled trial. METHODS: This prospective controlled study was carried out on patients who underwent septoplasty. Patients participating in the study were divided into 2 groups; group 1: classic septoplasty (n: 25) and group 2: extracorporeal septoplasty (n: 14). The sinonasal outcome test-22 (SNOT-22), peak nasal flowmetry, and Connecticut Chemosensory Clinical Research Center test were applied to all patients before and 8 weeks after surgery. Surgical outcomes also assessed to evaluate complications 6 months after surgery. RESULT: In total, 39 (27 males, 12 females) patients diagnosed with nasal septum deviation were included in this study. A septoplasty was performed in all patients: 25 of them (18 males, 7 females; mean age = 29.4 [range, 23-50] years) underwent classic septoplasties and 14 (9 males, 5 females; mean age = 31.3 [range, 23-50] years) underwent extracorporeal septoplasties. Airway openness was achieved in all patients. As a result, the SNOT-22 scores, peak nasal inspiratory flowmeter results, and smell function scores showed significant improvements (P < 0.001). CONCLUSION: All corrective surgical methods for a septum deviation have positive effects on nasal airflow, quality of life, and olfaction. The rates of complications were not significantly different between 2 treatment groups.

Unilateral endonasal transcribriform approach with septal transposition for olfactory groove meningioma: can olfaction be preserved?

BACKGROUND: Loss of olfaction has been considered inevitable in endoscopic endonasal resection of olfactory groove meningiomas. Olfaction preservation may be feasible through an endonasal unilateral transcribriform approach, with the option for expansion using septal transposition and contralateral preservation of the olfactory apparatus. METHODS: An expanded unilateral endonasal transcribriform approach with septal transposition was performed in five cadaver heads. The approach was applied in a surgical case of a 24 × 26-mm olfactory groove meningioma originating from the right cribriform plate with partially intact olfaction. RESULTS: The surgical approach offered adequate exposure to the anterior skull base bilaterally. The nasal/septal mucosa was preserved on the contralateral side. Gross total resection of the meningioma was achieved with the successful preservation of the contralateral olfactory apparatus and preoperative olfaction. Six months later, the left nasal cavity showed no disruption of the mucosal lining and the right side was at the appropriate stage of healing for a harvested nasoseptal flap. One year later, the preoperative olfactory function was intact and favorably viewed by the patient. Objective testing of olfaction showed microsomia. CONCLUSIONS: Olfaction preservation may be feasible in the endoscopic endonasal resection of a unilateral olfactory groove meningioma through a unilateral transcribriform approach with septal transposition and preservation of the contralateral olfactory apparatus.

Evaluation of residual symptoms: A method to assess surgical outcomes for nasal polyposis.

BACKGROUND: The assessment of residual symptoms after endoscopic sinus surgery for nasal polyposis (NP) could be an accurate way to evaluate surgical outcomes. OBJECTIVE: To assess the residual symptoms and their severity at 6 weeks and 7 months after radical ethmoidectomy for NP. METHODS: Sixty-five patients who had surgery for NP were included in this prospective study. Six residual symptoms (nasal obstruction, anterior rhinorrhea, postnasal discharge, olfactory disturbances, facial pain, and cough) were assessed by using the validated Dysfonctionnement Nasal Chronique (French) or Chronic Nasal Dysfunction (English) questionnaire at 6 weeks and 7 months after surgery. Olfactory measurements were performed with the Sniffin' Stick test. A self-rating score of ≥1 was considered as "having a complaint." RESULTS: Radical ethmoidectomy for NP improved not only the number of symptoms but also the intensity of symptoms. Before surgery, 64 of 65 patients (98.46%) reported at least three of the six symptoms, whereas 26 patients (40%) reported six symptoms, 16 (24.62%) reported five symptoms, and 14 (21.54%) reported four symptoms. At 6 weeks and at 7 months after surgery, one-third of the patients had fewer than three symptoms. Olfactory disturbance remained the most mentioned postoperative disabling problem. Posterior discharge tended to become more pronounced at 7 months than at 6 weeks after surgery but remained considerably improved compared with the preoperative state. CONCLUSION: This information is useful to warn patients about the difficulty of getting rid of all symptoms and that there is a chance that some symptoms remain or even reappear after NP surgery.

How Many and Which Odor Identification Items Are Needed to Establish Normal Olfactory Function?

The establishment of normal olfactory function by means of a simple and reliable test is one method that could minimize olfactory test procedures in the clinic. This retrospective study analyzed the identification of 16 odors by 613 subjects (aged 18-96 years, 266 men) as a part of a complex olfactory test battery by which 183, 251, and 179 subjects were diagnosed with anosmia, hyposmia, or normosmia, respectively. Cinnamon was identified as the best scoring odor, that is, identified correctly by most normosmic subjects, but identified correctly by the fewest anosmic patients. An exact calculation of the optimum number of items needed for a diagnosis of normosmia resulted in 1 single odor identification item as being sufficient. The inclusion of more items is solely determined by the acceptable proportion of chance, which in a 4-alternative forced choice paradigm is only 1.6% with 3 odors. A proposed screening test using cinnamon, fish odor, and banana established normosmia at a sensitivity of 80.4% and a specificity of 84.3% and a negative predictive value of 91.3%.A positive test result reliably establishes normosmia providing a confidence basis to terminate olfactory assessments following the application of only 3 odor identification items.

[Specific anosmia as a principle of olfactory perception]. / Spezifische Anosmie als Prinzip olfaktorischer Wahrnehmung.

Specific anosmia, the inability to perceive a specific odor, while olfactory perception is otherwise intact, is known as a rather seldom phenomenon. By testing the prevalence of specific anosmia to 20 different odors in a sample of 1600 people, we were able to estimate the general prevalence of anosmia. This revealed that specific anosmia is not rare at all. In contrast, the general likelihood for specific anosmia approaches 1. In addition, specific anosmia can be very well reversed by "smell training" during the course of 3 months. To summarize, specific anosmia seems to be a rule, not an exception, of olfactory sensation. The lack of perception of certain odors may constitute a flexible peripheral filter mechanism, which can be adapted by exposure to odors.

Association of decreased rate of influenza vaccination with increased subjective olfactory dysfunction.

IMPORTANCE: Seasonal influenza causes significant morbidity and mortality, with cardiovascular and respiratory complications the most common among susceptible individuals. Upper respiratory tract infections (URIs) are known to precede olfactory dysfunction in some patients. To our knowledge, there has been no study assessing the possible relationship between influenza vaccination status and olfactory dysfunction. OBJECTIVE: To compare vaccination status of a group of patients with subjective olfactory dysfunction with that of a group of controls. DESIGN, SETTING, AND PARTICIPANTS: Retrospective medical record review and telephone survey in a matched case-control study. Forty-two patients were identified via diagnosis codes who presented to a tertiary care academic rhinologic center with subjective smell dysfunction over the course of 1 year. Only post-URI and idiopathic etiologies were included. Forty-two age-, sex-, and race/ethnicity-matched control patients were also selected. MAIN OUTCOMES AND MEASURES: Demographic data, influenza vaccination status, and smoking status were reviewed. χ² Testing was used. RESULTS: We were able to obtain vaccination data for 36 of 42 patients in the olfactory dysfunction group and 38 of 42 in the control group. Seven of the 36 (19%) in the olfactory dysfunction group had received the vaccine in the year prior to presentation compared with 16 of 38 (42%) in the control group (P = .04). CONCLUSIONS AND RELEVANCE: Influenza vaccination seems to be associated with a decreased rate of subjective olfactory dysfunction. This is a preliminary finding, and further studies would be needed to elucidate the exact role of influenza and influenza vaccination in patients with olfactory loss.

Olfactory disruption: toward controlling important insect vectors of disease.

Chemical repellents are used to decrease contacts between insect disease vectors and their hosts, thus reducing the probability of disease transmission. The molecular mechanisms by which repellents have their effects are poorly understood and remain a controversial topic. Here, we present recent results of studies aimed at a more thorough understanding of the mode of action of repellents and discuss the implications of these findings for future research and development of novel or improved repellents.

Repair of nasal septal perforation using middle turbinate flap (monopedicled superiory based bone included conchal flap): a new unilateral middle turbinate mucosal flap technique.

UNLABELLED: The purpose of this study is to present a new approach for treatment of nasal septal perforation using middle turbinate flap. A consecutive study with follow-up of 31 patients with nasal septal perforation treated using middle turbinate flap. All patients underwent an endoscopic repair of nasal septal perforation using middle turbinate flap. All patients were followed for 18-24 months. Complete closure of the perforation was achieved in 29 of the 31 patients. Complete failure of the repair was observed in two patients. All patients showed nasal crusting in varying degrees for a period of 2-4 weeks. None of the patients showed nasal obstruction or atrophic rhinitis symptoms (stuffy nose, purulent postnasal drip, nasal crusting, epistaxis and anosmia) in postoperative follow-up. This technique provides a new method with many advantages compared to other techniques for closure of septal perforations. LEVEL OF EVIDENCE: IV.

Olfactory outcomes after endoscopic pituitary surgery with nasoseptal "rescue" flaps: electrocautery versus cold knife.

BACKGROUND: Olfaction has been shown to have a large impact on patients' lives. Endoscopic pituitary surgery is associated with potentially significant damage to olfactory tissues. The objective of this study was to determine the effect of cauterization on olfactory function when performing endoscopic pituitary surgery with a nasoseptal "rescue" flap. METHODS: A retrospective review was performed of prospectively collected data. Olfaction was the primary outcome and was measured using the subjective visual analog scale (VAS; 0-100) and Cross-Cultural Smell Identification Test (CC-SIT) before and 3 months after surgery. Significant olfactory deficit was defined as >20% loss compared with preoperative functions. Patients who underwent an endoscopic transsphenoidal approach with NSRFs for pituitary adenoma from June 2012 to March 2013 were included. Included patients were divided into two groups; group 1 underwent rescue flaps raised by monopolar cautery and group 2 underwent rescue flaps by cold knife. RESULTS: Forty-nine patients were included in this study. There were 19 patients in group 1 and 30 patients in group 2. There was no significant difference in subjective olfactory change between the two groups (p = 0.386; group 1, 13.68 ± 17.7, versus group 2, 6.83 ± 8.25). However, 5 of 19 patients (26.3%) had significant olfactory loss in group 1 and 1 of 30 (3.3%) in group 2. This difference was statistically significant (p = 0.027). None of the patients showed a significant decrease in CC-SIT score. CONCLUSION: Raising the rescue flap by cold knife could reduce the rate of hyposmia compared with using an electrocautery postoperatively.

Olfactory outcomes in chronic rhinosinusitis with nasal polyposis after medical treatments: a systematic review and meta-analysis.

BACKGROUND: Olfactory dysfunction is common among patients with chronic rhinosinusitis and has a negative impact upon quality of life. Olfactory dysfunction can be both subjective and objective and appears to be more predominant in patients with concomitant nasal polyposis. The efficacy of medical interventions on olfaction among patients with CRS with nasal polyposis (CRSwNP) is not well known. Our aim was to perform a systematic review with meta-analysis of the efficacy of medical therapies on objective and subjective hyposmia among patients with CRSwNP. METHODS: Olfaction specific outcomes from randomized controlled trials evaluating medical interventions on patients with CRSwNP were evaluated. Interventions included corticosteroids, antibacterials, antifungals, diuretics, herbals and anti-immunoglobulin E (IgE) medications. RESULTS: A total of 28 randomized control trials evaluation olfaction in CRSwNP was identified and systematically reviewed. Sufficient data for meta-analysis was retrieved for 5 trials. In the meta-analysis, oral steroids showed significant improvement in subjective olfaction scores compared to placebo (standardized mean difference [SMD] -2.22; 95% confidence interval [CI], -3.94 to -0.49). Oral steroids also showed significant improvement in objective olfaction scores compared to placebo (SMD 0.65; 95% CI, 0.28 to 1.01). In the systematic review, both topical steroids and combined topical and oral steroid groups showed overall improvement in subjective olfaction outcomes. Antibacterials, antifungals, herbals, and anti-IgE medications had no impact on overall olfaction scores. CONCLUSION: The results of this meta-analysis demonstrated that oral and topical steroids significantly improve olfaction in patients suffering from CRSwNP.

A novel mitochondrially-targeted apocynin derivative prevents hyposmia and loss of motor function in the leucine-rich repeat kinase 2 (LRRK2(R1441G)) transgenic mouse model of Parkinson's disease.

Recently, we demonstrated that dimeric apocynin prevented loss of motor function in the leucine-rich repeat kinase 2 (LRRK2(R1441G)) transgenic (tg) mouse (treated with 200mg/kg, three times per week) [B.P. Dranka et al., Neurosci. Lett. 549 (2013) 57-62]. Here we extend those studies by treating LRRK2(R1441G) mice with an orally-available, mitochondrially-targeted apocynin derivative. We hypothesized that the increased mitochondrial permeability of Mito-apocynin, due to the triphenylphosphonium moiety, would allow improvement of Parkinson's disease (PD) symptoms at lower doses than those required for diapocynin. Tests of motor coordination (pole test, Rotor-Rod) revealed a significant deficit in coordinated motor function in LRRK2(R1441G) mice by 15 months of age. Decreased performance on the pole test and Rotor-Rod in the LRRK2(R1441G) mice was prevented with Mito-apocynin treatment (3mg/kg, three times per week). Decreased olfactory function is an early indication of PD in human patients. LRRK2(R1441G) tg mice displayed deficits in sense of smell in both the hidden treat test, and a radial arm maze test. Interestingly, treatment with Mito-apocynin prevented this hyposmia, and animals retained normal ability to identify either a scented treat or a food pellet as well as wild type littermates. Together, these data demonstrate that the mitochondria-targeted apocynin analog is effective in preventing early PD-like symptoms in the LRRK2(R1441G) mouse model.

[Olfactory function in old age]. / Riechvermögen im Alter.

Olfactory function decreases with age. This is frequent: one in four individuals above 52 years of age exhibits olfactory loss. This decrease in olfactory function can be seen at all levels of olfactory information processing, both on a functional and a morphological level. Recent studies, however, indicate that olfactory loss with age may not be an inevitable fate.