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.

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.

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.

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.

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.

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.

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.