Trigeminal function in patients with COVID-associated olfactory loss.

PURPOSE: Olfactory dysfunction (OD) can be a long-term consequence of various viral infections, including COVID-19. Dysfunction includes hyposmia/anosmia and parosmia (odor distortions). Interactions of the virus with the olfactory nerve have been extensively researched, but little is known about the interactions of the intranasal trigeminal nerve system in modulating this sensory loss. METHODS: We investigated intranasal trigeminal function across COVID-19 OD patients with and without parosmia compared to normosmic controls, to determine whether (1) post-viral hyposmia and/or (2) post-viral hyposmia with parosmia is associated with altered trigeminal function. OD patients (n = 27) were tested for olfactory function using the extended Sniffin' Sticks olfactory test and for trigeminal function through three methods-odor lateralization, subjective ratings of nasal patency, and ammonium vapor pain intensity ratings. This group was subsequently compared to controls, normosmic subjects (n = 15). RESULTS: Our findings revealed that post-COVID OD patients without parosmia experienced decreased sensitivity in ammonium vapor pain intensity ratings and odor lateralization scores-but similar nasal patency ratings-compared to normosmic controls. There were no significant differences in trigeminal function between OD patients with and without parosmia. CONCLUSIONS: Based on our results, we conclude that the trigeminal nerve dysfunction may partially explain post-viral OD, but does not seem to be a major factor in the generation of parosmia pathophysiology.

Position paper on olfactory dysfunction: 2023

BACKGROUND: Since publication of the original Position Paper on Olfactory Dysfunction in 2017 (PPOD-17), the personal and societal burden of olfactory disorders has come sharply into focus through the lens of the COVID-19 pandemic. Clinicians, scientists and the public are now more aware of the importance of olfaction, and the impact of its dysfunction on quality of life, nutrition, social relationships and mental health. Accordingly, new basic, translational and clinical research has resulted in significant progress since the PPOD-17. In this updated document, we present and discuss currently available evidence for the diagnosis and management of olfactory dysfunction. Major updates to the current version include, amongst others: new recommendations on olfactory related terminology; new imaging recommendations; new sections on qualitative OD and COVID-19 OD; updated management section. Recommendations were agreed by all co-authors using a modified Delphi process. CONCLUSIONS: We have provided an overview of current evidence and expert-agreed recommendations for the definition, investigation, and management of OD. As for our original Position Paper, we hope that this updated document will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency, and generalisability of work in this field.

Developing a core outcome set for clinical trials in olfactory disorders: a COMET initiative.

STATEMENT OF PROBLEM: Evaluating the effectiveness of the management of Olfactory Dysfunction (OD) has been limited by a paucity of high-quality randomised and/or controlled trials. A major barrier is heterogeneity of outcomes in such studies. Core outcome sets (COS) - standardized sets of outcomes that should be measured/reported as determined by consensus-would help overcome this problem and facilitate future meta-analyses and/or systematic reviews (SRs). We set out to develop a COS for interventions for patients with OD. METHODS: A long-list of potential outcomes was identified by a steering group utilising a literature review, thematic analysis of a wide range of stakeholders' views and systematic analysis of currently available Patient Reported Outcome Measures (PROMs). A subsequent e-Delphi process allowed patients and healthcare practitioners to individually rate the outcomes in terms of importance on a 9-point Likert scale. RESULTS: After 2 rounds of the iterative eDelphi process, the initial outcomes were distilled down to a final COS including subjective questions (visual analogue scores, quantitative and qualitative), quality of life measures, psychophysical testing of smell, baseline psychophysical testing of taste, and presence of side effects along with the investigational medicine/device and patient's symptom log. CONCLUSIONS: Inclusion of these core outcomes in future trials will increase the value of research on clinical interventions for OD. We include recommendations regarding the outcomes that should be measured, although future work will be required to further develop and revalidate existing outcome measures.

Mechanisms and solutions for nasal drug delivery - a narrative review.

The aim of this paper is to review mechanisms and solutions for nasal drug delivery. Literature survey was performed via PubMed, Google Scholar, Google, and ProQuest Central database of Kirikkale University. The nasal lining presents a large area of endothelium of variable permeability and with a rich vascular supply. Advantages of this route include eliminating first-pass metabolism and being easily accessible. The nasal route enables some agents which are otherwise difficult to administer to enter the systemic circulation, for example, low molecular mass compounds with high polarity, peptides, or proteins. There are three principal factors that influence the extent to which drugs can be absorbed through the nasal lining, namely the physico-chemical characteristics of the drug molecule itself, the action of the mucociliary system within the nose, and the presence of any factors increasing nasal absorption. A key factor limiting the use of the intranasal route of administration is insufficient absorption through the nasal mucosa. A number of drugs in development cannot be administered intranasally because their bioavailability following nasal administration is too low. There has been considerable research focus on methods to enhance absorption via the nasal mucosa. In this chapter, we review the literature related to this problem and discuss potential solutions.

Hedonic perception of odors in children aged 5-8 years is similar across 18 countries: Preliminary data.

OBJECTIVE: Olfactory preference emerges very early in life, and the sense of smell in children rapidly develops until the second decade of life. It is still unclear whether hedonic perception of odors is shared in children inhabiting different regions of the globe. METHODS: Five-hundred ten healthy children (N = 510; ngirls = 256; nboys = 254) aged from 5 to 8 years from 18 countries rated the pleasantness of 17 odors. RESULTS: The hedonic perception of odors in children aged between 5 and 8 years was rather consistent across 18 countries and mainly driven by the qualities of an odor and the overall ability of children to label odorants. CONCLUSION: Conclusions from this study, being a secondary analysis, are limited to the presented set of odors that were initially selected for the development of U-Sniff test and present null findings for the cross-cultural variability in hedonic perception of odors across 18 countries. These two major issues should be addressed in the future to either contradict or replicate the results presented herewith. This research lays fundament for posing further research questions about the developmental aspects of hedonic perception of odors and opens a new door for investigating cross-cultural differences in chemosensory perception of children.

Role of spreader flaps in primary rhinoplasty, functional and aesthetic outcomes: a systematic review.

BACKGROUND: The standard treatment for reconstructing the middle vault of the nose is to use spreader grafts. Recently, an alternative technique using spreader flaps has become widely accepted. METHODOLOGY: A literature search was performed in MEDLINE, Science Direct, the Cochrane Library and multiple trial registries. The systematic review included studies evaluating the effectiveness of spreader flaps, with or without comparison to the spreader graft technique, in patients who had undergone primary rhinoplasty. RESULTS: Thirteen studies with a total of 500 patients met the inclusion criteria and were reviewed systematically. All studies measured breathing function improvement. Additionally, aesthetic improvement/satisfaction was evaluated in seven studies. The use of spreader flaps seems to improve breathing function, as seen in twelve out of thirteen studies. Furthermore, the studies assessing the aesthetic aspect of a primary rhinoplasty showed that spreader flaps can provide satisfactory results. The comparison between spreader flaps and spreader grafts showed similar results in most studies dealing with this topic in both the breathing function improvement and aesthetic improvement/satisfaction domains. CONCLUSIONS: This study is the first systematic review assessing the functional and aesthetic outcomes of spreader flaps in primary rhinoplasty, and it shows encouraging results comparable to those of spreader grafts.

Magnetic nanoparticles: An indicator of health risks related to anthropogenic airborne particulate matter.

Due to their small dimensions, airborne particles are able to penetrate through inhalation into many human organs, from the lungs to the cardiovascular system and the brain, which can threaten our health. This work establishes a novel approach of collecting quantitative data regarding the fraction, the composition and the size distribution of combustion-emitted particulate matter through the magnetic characterization and analysis of samples received by common air pollution monitoring. To this end, SQUID magnetometry measurements were carried out for samples from urban and suburban areas in Thessaloniki, the second largest city of Greece, taking into consideration the seasonal and weekly variation of airborne particles levels as determined by occurring traffic and meteorological conditions. The level of estimated magnetically-responding atmospheric particulate matter was at least 0.5 % wt. of the collected samples, mostly being present in the form of ultrafine particles with nuclei sizes of approximately 14 nm and their aggregates. The estimated quantities of magnetic particulate matter show maximum values during autumn months (0.8 % wt.) when increased commuting takes place, appearing higher in the city center by up to 50% than those in suburban areas. In combination with high-resolution transmission electron imaging and elemental analysis, it was found that Fe3O4 and similar ferrites, some of them attached to heavy metals (Co, Cr), are the dominant magnetic contributors arising from anthropogenic high-temperature processes, e.g. due to traffic emissions. Importantly, nasal cytologic samples collected from residents of both central and suburban areas showed same pattern in what concerns magnetic behavior, thus verifying the critical role of nanosized magnetic particles in the assessment of air pollution threats. Despite the inherent statistical limitations of our study, such findings also indicate the potential transmission of infectious pathogens by means of pollution-derived nanoparticles into the respiratory system of the human body.

Comparison of COVID-19 and common cold chemosensory dysfunction.

Anosmia constitutes a prominent symptom of COVID-19. However, anosmia is also a common symptom of acute colds of various origins. In contrast to an acute cold, it appears from several questionnaire-based studies that in the context of COVID-19 infection, anosmia is the main rhinological symptom and is usually not associated with other rhinological symptoms such as rhinorrhoea or nasal obstruction. Until now, no study has directly compared smell and taste function between COVID-19 patients and patients with other causes of upper respiratory tract infection (URTI) using valid and reliable psychophysical tests. In this study, we aimed to objectively assess and compare olfactory and gustatory functions in 10 COVID-19 patients (PCR diagnosed, assessed on average 2 weeks after infection), 10 acute cold (AC) patients (assessed before the COVID-19 outbreak) and 10 healthy controls, matched for age and sex. Smell performance was assessed using the extended "Sniffin' Sticks" test battery (4), while taste function was assessed using "taste strips" (5). Receiver Operating Characteristic (ROC) curves were built to probe olfactory and gustatory scores in terms of their discrimination between COVID-19 and AC patients. Our results suggest that mechanisms of COVID-19 related olfactory dysfunction are different from those seen in an AC and may reflect, at least to some extent, a specific involvement at the level of central nervous system in some COVID-19 patients. In the future, studies to assess the prevalence of persistent anosmia and neuroanatomical changes on MRI correlated to chemosensory function, will be useful to understand these mechanisms.

Development of a new psychophysical method to assess intranasal trigeminal chemosensory function.

BACKGROUND: The aim of this study was to develop a new psychophysical test to assess intranasal trigeminal chemosensory function. METHODOLOGY: The test is similar to the Sniffin’ Sticks test, but using pens impregnated with substances preferentially activating trigeminal afferents. Our test comprises detection threshold, discrimination, identification and lateralization tasks. In a first study, we evaluated healthy controls. In a second study, we evaluated the potential usefulness of this test in patients with rhinological conditions. RESULTS: Study 1: 86 controls were included. Threshold, identification and lateralization performance decreased with age. Test-retest reliability was similar to that of olfactory tests. Study 2: results of the controls group were compared to those of 59 patients (14 allergic rhinitis, 11 chronic rhinosinusitis with nasal polyps (CRSwNP), 9 without nasal polyps (CRSsNP), and 25 with an olfactory disorder (OD)). Controls had 1) lower detection thresholds compared to CRSwNP, CRSsNP and OD, 2) better discrimination and identification scores compared to OD, and 3) better lateralization scores compared to CRSwNP and CRSsNP. CONCLUSIONS: Our test allows to identify age-related changes in trigeminal chemosensory function. Trigeminal function seems to be differently affected in different pathologies. Further studies are necessary to validate our results and evaluate the impact of olfactory co-activation on the observed results.

Disparities in survival after trimodality therapy for esophageal adenocarcinoma.

Trimodality therapy with neoadjuvant chemoradiation followed by surgery has emerged as the standard of care for the treatment of locally advanced esophageal cancer. Yet, there is considerable variation in survival within this population. We sought to analyze factors associated with survival after trimodality therapy in esophageal adenocarcinoma. We identified 4,679 patients from the National Cancer Database (NCDB) of the American College of Surgeons who received chemotherapy and radiation prior to surgery for esophageal adenocarcinoma from 2006 to 2013. We excluded patients with stage IV disease and unknown pathological nodal status. We performed regression analyses using a Cox proportional hazards model to identify independent predictors of overall survival. On multivariate analysis, pathologic characteristics associated with decreased overall survival included stage, lymphovascular invasion, and positive surgical margins. Insurance status, age, and comorbidity index were also associated with decreased survival. We found that pathologically node-positive patients who received additional adjuvant chemotherapy were associated with improved survival. Compared to private insurance, Medicaid (HR 1.45, CI 1.22-1.73, P < 0.0001), Medicare (HR 1.17, CI 1.04-1.31, P = 0.0082), or having no insurance (HR 1.50, CI 1.17-1.92, P = 0.0012) were all negative predictors of overall survival. In patients with esophageal adenocarcinoma who have undergone trimodality therapy, a number of different factors are associated with overall survival. In particular, socioeconomic factors relating to access to care are independent predictors of survival. Despite receiving the standard of care, treatment disparities persist in this population of patients.

Monoclonal antibodies for the treatment of chronic rhinosinusitis with nasal polyposis: a systematic review.

BACKGROUND: Monoclonal antibodies have been proposed as a novel therapy in patients suffering from chronic rhinosinusitis with nasal polyposis (CRSwNP). The purpose of this systematic review was to evaluate their efficacy and safety. METHODOLOGY: A literature search was performed in MEDLINE, Web of Science, the Cochrane Library and multiple trial registries followed by extensive hand-searching for the identification of relevant studies. Only randomized controlled trials (RCTs) comparing the use of monoclonal antibodies with placebo or another therapy in adult patients with CRSwNP were included. RESULTS: Anti-immunoglobin E (IgE) therapy with omalizumab was assessed in two studies, anti-interleukin (IL)-5 therapy in three studies (1 reslizumab, 2 mepolizumab) and finally anti-IL-4 and anti-IL-13 therapy in only one. With the exception of one study, biologic therapy was proved to be effective in reducing total nasal endoscopic polyp score (TPS) in treatment as compared to placebo groups. Monoclonal antibodies brought about improvement in several other outcomes, such as opacification in computed tomography (CT), quality of life measures, nasal airflow, olfaction and type 2 helper T-cell (Th2) associated biomarkers. Overall, the use of these agents was deemed safe and well-tolerated. CONCLUSIONS: This is the first systematic review showing encouraging results for the use of all three main categories of monoclonal antibodies in CRSwNP patients and highlights the need for further well-designed and with larger sample sizes RCTs.

Position paper on olfactory dysfunction.

Background: Olfactory dysfunction is an increasingly recognised condition, associated with reduced quality of life and major health outcomes such as neurodegeneration and death. However, translational research in this field is limited by heterogeneity in methodological approach, including definitions of impairment, improvement and appropriate assessment techniques. Accordingly, effective treatments for smell loss are limited. In an effort to encourage high quality and comparable work in this field, among others, we propose the following ideas and recommendations. Whilst the full set of recommendations are outlined in the main document, points include the following: • Patients with suspected olfactory loss should undergo a full examination of the head and neck, including rigid nasal endoscopy with small diameter endoscopes. • Subjective olfactory assessment should not be undertaken in isolation, given its poor reliability. • Psychophysical assessment tools used in clinical and research settings should include reliable and validated tests of odour threshold, and/or one of odour identification or discrimination. • Comprehensive chemosensory assessment should include gustatory screening. • Smell training can be helpful in patients with olfactory loss of several aetiologies. Conclusions: We hope the current manuscript will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency and generalisability of work in this field.

Pain and discomfort following immediate and delayed loading by overdentures in the single mandibular implant study (SMIS).

OBJECTIVES: This randomized clinical trial compares immediate and delayed loading of single implants to support mandibular overdentures. The aim of this preliminary analysis is to test the hypothesis whether patients with immediate loading will experience less pain and discomfort through the intervention than patients with delayed loading. MATERIALS AND METHODS: Edentulous patients in nine German dental schools received a midline implant with a length of 11 mm. Implants with a minimum insertion torque of 30 Ncm and an implant stability quotient of ≥60 were randomly allocated to group A for immediate loading using ball attachments or to group B for delayed loading after 3 months. Patients completed questionnaires with 100-mm visual analogue scales about the items pain, pain during chewing, swelling, bleeding, and perception of the intervention at the day of surgery and 1, 2, 3, and 7 days, thereafter. Groups were compared by Wilcoxon-Mann-Whitney tests (P ≤ 0.05). RESULTS: The questionnaires of 81 patients in group A and 74 patients in group B were completed. The medians for pain and discomfort were moderate (<30). Participants of group A felt significantly more pain from the first day and more swelling from the third day after implantation than participants of group B. The individual perception of interventions showed no significant differences between groups. CONCLUSIONS: Immediate loading evoked more postoperative pain and swelling than the two stages of delayed loading. CLINICAL RELEVANCE: Immediate loading of a single mandibular midline implant supporting overdentures should be carefully considered.

Long term effects of olfactory training in patients with post-infectious olfactory loss.

BACKGROUND: There is evidence of the effectiveness of repeated exposure to odours on short-term olfactory function. The aim of this study was to assess the long-term effects of olfactory training. METHODS: We conducted a prospective study of 111 patients with post-infectious olfactory dysfunction. Two groups of patients performed olfactory training for 16 and 56 weeks, respectively, and were compared with a control group. The training was performed twice daily using four odours (phenyl ethyl alcohol, eucalyptol, citronellal, eugenol). Olfactory testing was performed by means of the Sniffin Sticks test as a baseline assessment and then every 8 weeks for 56 weeks. Subjective ratings were performed using a visual analogue scale (0-100). RESULTS: Both training groups presented significantly higher scores than the controls. The long-term group had better results than the short-term group. Short-term training patients sustained their improvement within the follow-up period. Subsets analysis showed that training patients mainly increased identification and discrimination. Subjective ratings were in accordance with the olfactory test results. CONCLUSION: Long-term olfactory training seems to be associated with better results in patients with post-infectious olfactory loss than a short-term scheme. Short-term training provides sustainable results at 56 weeks follow-up assessment.

Outcomes of direct pulp capping: interrogating an insurance database.

AIM: To evaluate the effectiveness of direct pulp capping under general practice conditions. It was hypothesized that direct pulp capping is an effective procedure in the majority of cases and prevents the need for root canal treatment or extraction. METHODOLOGY: Claims data were collected from the digital database of a major German national health insurance company. Only patients who had been insurance members for the entire 3 year period 2010 to 2012 were eligible. Kaplan-Meier survival analyses were conducted for all teeth with direct pulp capping. Success was defined as not undergoing root canal treatment. Survival was defined as not undergoing extraction. Differences between survival functions were tested with the log rank test. RESULTS: A total of 148 312 teeth were included. The overall success rate was 71.6% at 3 years. The overall survival rate was 95.9% at 3 years. The success rates for single-rooted teeth (71.8%) and multirooted teeth (71.5%) were similar although significantly different (P < 0.001). Best 3-year success rates were found at low (79.7%; <18 years.) and very high age (81.8%; >85 years.). CONCLUSIONS: After direct pulp capping, more than two-thirds of the affected teeth did not undergo root canal treatment within 3 years. Although this study has the typical limits of a claims data analysis, it can be concluded that direct pulp capping is an effective intervention to avoid root canal treatment and extraction in a general practice setting.

Dialysis-requiring acute kidney injury among hospitalized adults with documented hepatitis C Virus infection: a nationwide inpatient sample analysis.

Chronic hepatitis C virus (HCV) infection may cause kidney injury, particularly in the setting of cryoglobulinemia or cirrhosis; however, few studies have evaluated the epidemiology of acute kidney injury in patients with HCV. We aimed to describe national temporal trends of incidence and impact of severe acute kidney injury (AKI) requiring renal replacement 'dialysis-requiring AKI' in hospitalized adults with HCV. We extracted our study cohort from the Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project using data from 2004 to 2012. We defined HCV and dialysis-requiring acute kidney injury based on previously validated ICD-9-CM codes. We analysed temporal changes in the proportion of hospitalizations complicated by dialysis-requiring AKI and utilized survey multivariable logistic regression models to estimate its impact on in-hospital mortality. We identified a total of 4,603,718 adult hospitalizations with an associated diagnosis of HCV from 2004 to 2012, of which 51,434 (1.12%) were complicated by dialysis-requiring acute kidney injury. The proportion of hospitalizations complicated by dialysis-requiring acute kidney injury increased significantly from 0.86% in 2004 to 1.28% in 2012. In-hospital mortality was significantly higher in hospitalizations complicated by dialysis-requiring acute kidney injury vs those without (27.38% vs 2.95%; adjusted odds ratio: 2.09; 95% confidence interval: 1.74-2.51). The proportion of HCV hospitalizations complicated by dialysis-requiring acute kidney injury increased significantly between 2004 and 2012. Similar to observations in the general population, dialysis-requiring acute kidney injury was associated with a twofold increase in odds of in-hospital mortality in adults with HCV. These results highlight the burden of acute kidney injury in hospitalized adults with HCV infection.

Position paper on olfactory dysfunction.

BACKGROUND: Olfactory dysfunction is an increasingly recognised condition, associated with reduced quality of life and major health outcomes such as neurodegeneration and death. However, translational research in this field is limited by heterogeneity in methodological approach, including definitions of impairment, improvement and appropriate assessment techniques. Accordingly, effective treatments for smell loss are limited. In an effort to encourage high quality and comparable work in this field, among others, we propose the following ideas and recommendations. Whilst the full set of recommendations are outlined in the main document, points include the following: - Patients with suspected olfactory loss should undergo a full examination of the head and neck, including rigid nasal endoscopy with small diameter endoscopes. - Subjective olfactory assessment should not be undertaken in isolation, given its poor reliability. - Psychophysical assessment tools used in clinical and research settings should include reliable and validated tests of odour threshold, and/or one of odour identification or discrimination. - Comprehensive chemosensory assessment should include gustatory screening. - Smell training can be helpful in patients with olfactory loss of several aetiologies. CONCLUSIONS: We hope the current manuscript will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency and generalisability of work in this field.

Evaluation and management of juvenile recurrent parotitis in children from northern Greece.

BACKGROUND: Juvenile Recurrent Parotitis (JRP) is a recurrent parotid inflammation of childhood.  The aim of our study was to investigate the clinical, laboratory and imaging profile of children with JRP as well as to estimate the impact of siadendoscopy as a therapeutic tool in the clinical outcome of JRP. METHODS: Twenty-three children with JRP aged 3.5-16 years, were investigated. Twelve of them underwent sialendoscopy: seven aged <8 years under general and five aged >8 years under local anesthesia. RESULTS: The age at onset ranged from 2-15 years while the number of episodes from 2-8 per year. The autoantibody profile was negative in all patients, suggesting no evidence for autoimmune diseases.  Antibody deficiency was found in two children. The imaging studies reveal an overall parotid swelling and intraparotid lymph nodes while microabscesses were present in 31% of the patients. Twelve patients who underwent sialendoscopy had a significant improvement in their clinical outcome; the mean episodes of JRP before sialendoscopy was 3.9/year and reduced to 0.4 at the post-intervention year. CONCLUSION: Sialendoscopy represents an alternative and promising perspective in the management of JRP. Hippokratia 2015; 19 (4): 356-359.

Long-term results of combined approach in parotid sialolithiasis.

Combined sialendoscopic and transcutaneous approach in parotid sialolithiasis is a surgical option for large and impacted stones. The aim of this study is to assess the long-term results regarding postoperative stenosis, recurrent swellings and gland function. Prospective study in a tertiary referral center of patients with parotid sialolithiasis requiring combined approach. A total of 12 patients have been treated within a period of 3 years. Intraductal stents were placed in 9 of 12 cases. Scintigraphic evaluation of salivary glands and follow-up sialendoscopy performed 1 year postoperatively. In total, fourteen stones (two stones in two cases) were successfully removed along with two coexisted inflammatory polyps. Postoperative endoscopic evaluation revealed mild stenosis in 7 out of 12 cases without clinical significance as no recurrent swellings were reported. Scintigraphy showed normal gland function in 11 cases and mild hypofunction in 1 case with long-standing history of sialolithiasis. All patients were free of symptoms within the follow-up period of time (median follow-up 15.5 months). Combined approach is a safe, gland preserving and efficacious procedure in long term. The stenosis in the area of ductal surgical opening when present does not seem to be of clinical value.