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The Laryngoscope Jun 2022Olfactory dysfunction (OD) is a common presenting symptom of COVID-19 infection. Radiological imaging of the olfactory structures in patients with COVID-19 and OD can... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Olfactory dysfunction (OD) is a common presenting symptom of COVID-19 infection. Radiological imaging of the olfactory structures in patients with COVID-19 and OD can potentially shed light on its pathogenesis, and guide clinicians in prognostication and intervention.
METHODS
PubMed, Embase, Cochrane, SCOPUS were searched from inception to August 1, 2021. Three reviewers selected observational studies, case series, and case reports reporting radiological changes in the olfactory structures, detected on magnetic resonance imaging, computed tomography, or other imaging modalities, in patients aged ≥18 years with COVID-19 infection and OD, following preferred reporting items for systematic reviews and meta-analyses guidelines and a PROSPERO-registered protocol (CRD42021275211). We described the proportion of radiological outcomes, and used random-effects meta-analyses to pool the prevalence of olfactory cleft opacification, olfactory bulb signal abnormalities, and olfactory mucosa abnormalities in patients with and without COVID-19-associated OD.
RESULTS
We included 7 case-control studies (N = 353), 11 case series (N = 154), and 12 case reports (N = 12). The pooled prevalence of olfactory cleft opacification in patients with COVID-19 infection and OD (63%, 95% CI = 0.38-0.82) was significantly higher than that in controls (4%, 95% CI = 0.01-0.13). Conversely, similar proportions of cases and controls demonstrated olfactory bulb signal abnormalities (88% and 94%) and olfactory mucosa abnormalities (2% and 0%). Descriptive analysis found that 55.6% and 43.5% of patients with COVID-19 infection and OD had morphological abnormalities of the olfactory bulb and olfactory nerve, respectively, while 60.0% had abnormal olfactory bulb volumes.
CONCLUSION
Our findings implicate a conductive mechanism of OD, localized to the olfactory cleft, in approximately half of the affected COVID-19 patients. Laryngoscope, 132:1260-1274, 2022.
Topics: Adolescent; Adult; COVID-19; Humans; Olfaction Disorders; Olfactory Bulb; Olfactory Mucosa; Smell
PubMed: 35318656
DOI: 10.1002/lary.30078 -
Cureus Jan 2023The objective of this systematic review was to investigate the expression of angiotensin converting enzyme 2 (ACE 2) in the head and neck region. We examined the... (Review)
Review
The objective of this systematic review was to investigate the expression of angiotensin converting enzyme 2 (ACE 2) in the head and neck region. We examined the evidence of the association of ACE 2 expression in oral tissues, salivary glands, and head and neck carcinoma. We searched Pub Med/Medline, Biorxiv, and Google Scholar to identify relevant literature. Studies reporting ACE 2 expression in human oral tissues and with a focus on head and neck carcinoma samples were included. From 110 studies, we extracted 15 studies analyzing the distribution and expression of ACE 2 in different head and neck tissues - olfactory mucosa and nasopharynx n=5, oral mucosa n=5, salivary gland n=5, head and neck squamous cell carcinoma patients n=3. ACE 2 was found to be expressed at a 4.43-fold increase in the head and neck region (OR, 4.43; 95% CI, 3.76-5.22; I= 97%, P=<0.00001) when compared with controls (other tissues except for head and neck region). RNA expression of ACE 2 was 60% higher in head and neck squamous cell carcinoma patients than that in the normal tissues (OR=0.60, 95% CI, 0.04-9.26, P=0.00001). In conclusion, the meta-analysis of the studies indicated that ACE 2 is highly expressed in olfactory mucosa, nasopharynx, oral mucosa, and salivary glands. Furthermore, the results indicate that ACE 2 expression is increased in patients with head and neck cancer.
PubMed: 36819393
DOI: 10.7759/cureus.33673 -
American Journal of Rhinology & Allergy May 2021Post-viral olfactory dysfunction is a common cause of both short- and long-term smell alteration. The coronavirus pandemic further highlights the importance of...
BACKGROUND
Post-viral olfactory dysfunction is a common cause of both short- and long-term smell alteration. The coronavirus pandemic further highlights the importance of post-viral olfactory dysfunction. Currently, a comprehensive review of the neural mechanism underpinning post-viral olfactory dysfunction is lacking.
OBJECTIVES
To synthesize the existing primary literature related to olfactory dysfunction secondary to viral infection, detail the underlying pathophysiological mechanisms, highlight relevance for the current COVID-19 pandemic, and identify high impact areas of future research.
METHODS
PubMed and Embase were searched to identify studies reporting primary scientific data on post-viral olfactory dysfunction. Results were supplemented by manual searches. Studies were categorized into animal and human studies for final analysis and summary.
RESULTS
A total of 38 animal studies and 7 human studies met inclusion criteria and were analyzed. There was significant variability in study design, experimental model, and outcome measured. Viral effects on the olfactory system varies significantly based on viral substrain but generally include damage or alteration in components of the olfactory epithelium and/or the olfactory bulb.
CONCLUSIONS
The mechanism of post-viral olfactory dysfunction is highly complex, virus-dependent, and involves a combination of insults at multiple levels of the olfactory pathway. This will have important implications for future diagnostic and therapeutic developments for patients infected with COVID-19.
Topics: Animals; COVID-19; Humans; Olfaction Disorders; Olfactory Bulb; Olfactory Mucosa; Olfactory Pathways; SARS-CoV-2; Species Specificity; Post-Acute COVID-19 Syndrome
PubMed: 32915650
DOI: 10.1177/1945892420957853 -
Scientific Reports Jan 2018There are considerable disagreements on the application of olfactory ensheathing cells (OEC) for spinal cord injury (SCI) rehabilitation. The present meta-analysis was... (Meta-Analysis)
Meta-Analysis Review
There are considerable disagreements on the application of olfactory ensheathing cells (OEC) for spinal cord injury (SCI) rehabilitation. The present meta-analysis was designed to investigate the efficacy of OEC transplantation on motor function recovery and neuropathic pain alleviation in SCI animal models. Accordingly, all related studies were identified and included. Two independent researchers assessed the quality of the articles and summarized them by calculating standardized mean differences (SMD). OEC transplantation was shown to significantly improve functional recovery (SMD = 1.36; 95% confidence interval: 1.05-1.68; p < 0.001). The efficacy of this method was higher in thoracic injuries (SMD = 1.41; 95% confidence interval: 1.08-1.74; p < 0.001) and allogeneic transplants (SMD = 1.53; 95% confidence interval: 1.15-1.90; p < 0.001). OEC transplantation had no considerable effects on the improvement of hyperalgesia (SMD = -0.095; 95% confidence interval: -0.42-0.23; p = 0.57) but when the analyses were limited to studies with follow-up ≥8 weeks, it was associated with increased hyperalgesia (SMD = -0.66; 95% confidence interval: -1.28-0.04; p = 0.04). OEC transplantation did not affect SCI-induced allodynia (SMD = 0.54; 95% confidence interval: -0.80-1.87; p = 0.43). Our findings showed that OEC transplantation can significantly improve motor function post-SCI, but it has no effect on allodynia and might lead to relative aggravation of hyperalgesia.
Topics: Animals; Cell Transplantation; Humans; Neuralgia; Olfactory Bulb; Olfactory Mucosa; Spinal Cord Injuries
PubMed: 29321494
DOI: 10.1038/s41598-017-18754-4 -
Ear, Nose, & Throat Journal Nov 2023To summarize the current applications and potential uses of optical coherence tomography (OCT), a noninvasive imaging modality that uses near-infrared light to produce... (Review)
Review
To summarize the current applications and potential uses of optical coherence tomography (OCT), a noninvasive imaging modality that uses near-infrared light to produce cross-sectional, high-resolution images of biologic tissues, for evaluating the sinonasal mucosa in patients. Original articles utilizing OCT to image the sinonasal mucosa in patients were identified from the PubMed, Embase, Cochrane Library, Web of Science, and Scopus databases using the search phrase: "Optical Coherence Tomography" AND (sinonasal OR intranasal OR sinus OR nose OR sinusitis OR rhinitis OR olfactory). Strength of evidence, quality of evidence, and risk of bias were measured using validated scales. Study results were qualitatively assessed. Out of 1662 original records identified through database searching, 9 studies were included in the systematic review. Levels of evidence ranged from III to IV and quality of evidence ranged from moderate to very low. Endoscopic OCT systems as well as OCT systems integrated with surgical microscopes were described in the literature. Applications of OCT for imaging the sinonasal mucosa included identifying morphological patterns unique to individual diseases, detecting mucosal structural changes after medical therapies and procedures, and evaluating mucociliary clearance. Most studies investigating OCT imaging of the sinonasal mucosa featured small sample sizes and lacked control groups. While OCT imaging could be a useful adjunct for diagnosing sinonasal disorders and monitoring response to treatment in the future, additional high-quality studies are necessary to determine if the use of OCT imaging can lead to improved diagnostic accuracy and health outcomes for patients with sinonasal pathologies.
PubMed: 38032064
DOI: 10.1177/01455613231214622 -
International Journal of Molecular... Jun 2021FcRn plays a major role in regulating immune homeostasis, but it is also able to transport biologics across cellular barriers. The question of whether FcRn could be an... (Meta-Analysis)
Meta-Analysis
FcRn plays a major role in regulating immune homeostasis, but it is also able to transport biologics across cellular barriers. The question of whether FcRn could be an efficient transporter of biologics across the nasal epithelial barrier is of particular interest, as it would allow a less invasive strategy for the administration of biologics in comparison to subcutaneous, intramuscular or intravenous administrations, which are often used in clinical practice. A focused systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. It was registered on the international prospective register of systematic reviews PROSPERO, which helped in identifying articles that met the inclusion criteria. Clinical and preclinical studies involving FcRn and the nasal delivery of biologics were screened, and the risk of bias was assessed across studies using the Oral Health Assessment Tool (OHAT). Among the 12 studies finally included in this systematic review (out of the 758 studies screened), 11 demonstrated efficient transcytosis of biologics through the nasal epithelium. Only three studies evaluated the potential toxicity of biologics' intranasal delivery, and they all showed that it was safe. This systematic review confirmed that FcRn is expressed in the nasal airway and the olfactory epithelium, and that FcRn may play a role in IgG and/or IgG-derived molecule-transcytosis across the airway epithelium. However, additional research is needed to better characterize the pharmacokinetic and pharmacodynamic properties of biologics after their intranasal delivery.
Topics: Animals; Biological Products; Biological Transport; Biomarkers; Drug Delivery Systems; Gene Expression; Histocompatibility Antigens Class I; Humans; Nasal Mucosa; Protein Binding; Receptors, Fc; Transcytosis
PubMed: 34204226
DOI: 10.3390/ijms22126475 -
Biology Apr 2023The devastating effects of Alzheimer's disease (AD) are yet to be ameliorated due to the absence of curative treatment options. AD is an aging-related disease that...
The devastating effects of Alzheimer's disease (AD) are yet to be ameliorated due to the absence of curative treatment options. AD is an aging-related disease that affects cognition, and molecular imbalance is one of its hallmarks. There is a need to identify common causes of molecular imbalance in AD and their potential mechanisms for continuing research. A narrative synthesis of molecular mechanisms in AD from primary studies that employed single-cell sequencing (scRNA-seq) or spatial genomics was conducted using Embase and PubMed databases. We found that differences in molecular mechanisms in AD could be grouped into four key categories: sex-specific features, early-onset features, aging, and immune system pathways. The reported causes of molecular imbalance were alterations in bile acid (BA) synthesis, PITRM1, TREM2, olfactory mucosa (OM) cells, cholesterol catabolism, NFkB, double-strand break (DSB) neuronal damage, P65KD silencing, tau and APOE expression. What changed from previous findings in contrast to results obtained were explored to find potential factors for AD-modifying investigations.
PubMed: 37106802
DOI: 10.3390/biology12040602 -
Head and Neck Pathology Mar 2021To review the data regarding the expression of angiotensin converting enzyme-2 (ACE2) and transmembrane protease serine-2 (TMPRSS2) in head and neck tissue. Scopus,...
To review the data regarding the expression of angiotensin converting enzyme-2 (ACE2) and transmembrane protease serine-2 (TMPRSS2) in head and neck tissue. Scopus, Cochrane Library, Medrxiv, Google Scholar and PubMED/MEDLINE were searched by four independent investigators for studies investigating ACE2 or TMPRSS2 expressions in head and neck tissues. The following outcomes were considered: sample origin (animal versus human); detection method; anatomical location and cell types. PRISMA checklist and modified population, intervention, comparison, outcome, timing and setting (PICOTS) framework were used to perform the review. Of the 24 identified studies, 17 met our inclusion criteria. Thirteen studies were conducted during the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic. ACE2 and TMPRSS2 were expressed in oral, pharyngeal, sinusonasal human mucosa. The following cell types expressed ACE2: basal, apical, goblet, minor salivary, and endothelial cells. TMPRSS2 was found in goblet and apical respiratory cells. ACE2 and TMPRSS2 were found in the olfactory region, especially in sustentacular non-neural and neural stem cells. Animal studies suggested that ACE2 expression may vary regarding age. There was an important heterogeneity between studies in the methods used to detect ACE2 and TMPRSS2, leading to a potential identification bias. The SARS-CoV-2 receptors, ACE2 and TMPRSS2, are both expressed in many head and neck tissues, enabling the viral entry into the host organism.
Topics: Angiotensin-Converting Enzyme 2; Animals; COVID-19; Head; Humans; Neck; SARS-CoV-2; Serine Endopeptidases
PubMed: 32816230
DOI: 10.1007/s12105-020-01212-5 -
Acta Otorrinolaringologica Espanola 2020There is debate as to whether olfactory dysfunction should be considered a symptom of COVID-19 infection, given the implications for managing the symptom itself, for...
There is debate as to whether olfactory dysfunction should be considered a symptom of COVID-19 infection, given the implications for managing the symptom itself, for diagnostic testing, and for implementing isolation measures. We undertook a systematic literature review of the articles indexed in PubMed on olfactory disorders in viral respiratory tract conditions, with special emphasis on COVID-19. The main objective was to find evidence of clinical interest to support the relationship between anosmia and COVID-19. Olfactory disorders in upper respiratory tract infections are frequent, most caused by obstruction due to oedema of the nasal mucosa. Occasionally, post-viral sensorineural olfactory dysfunction occurs, with a variable prognosis. The evidence on anosmia in COVID-19 patients is extremely limited, corresponding to a level 5 or D of the Centre for Evidence-Based Medicine. According to the various medical societies that have issued reports on the subject, it seems reasonable to apply isolation, hygiene and social distancing measures in patients with recent olfactory disorders as the only symptom, although the usefulness of diagnostic tests for this type of patient should be studied.
Topics: Betacoronavirus; COVID-19; COVID-19 Testing; Clinical Laboratory Techniques; Coronavirus Infections; Humans; Hygiene; Olfaction Disorders; Olfactory Mucosa; Pandemics; Patient Isolation; Pneumonia, Viral; Practice Guidelines as Topic; Prognosis; Quarantine; Respiratory Tract Infections; SARS-CoV-2; Virus Diseases
PubMed: 32466862
DOI: 10.1016/j.otorri.2020.04.003 -
International Journal of Nanomedicine 2024Addressing disorders related to the central nervous system (CNS) remains a complex challenge because of the presence of the blood-brain barrier (BBB), which restricts...
Addressing disorders related to the central nervous system (CNS) remains a complex challenge because of the presence of the blood-brain barrier (BBB), which restricts the entry of external substances into the brain tissue. Consequently, finding ways to overcome the limited therapeutic effect imposed by the BBB has become a central goal in advancing delivery systems targeted to the brain. In this context, the intranasal route has emerged as a promising solution for delivering treatments directly from the nose to the brain through the olfactory and trigeminal nerve pathways and thus, bypassing the BBB. The use of lipid-based nanoparticles, including nano/microemulsions, liposomes, solid lipid nanoparticles, and nanostructured lipid carriers, has shown promise in enhancing the efficiency of nose-to-brain delivery. These nanoparticles facilitate drug absorption from the nasal membrane. Additionally, the in situ gel (ISG) system has gained attention owing to its ability to extend the retention time of administered formulations within the nasal cavity. When combined with lipid-based nanoparticles, the ISG system creates a synergistic effect, further enhancing the overall effectiveness of brain-targeted delivery strategies. This comprehensive review provides a thorough investigation of intranasal administration. It delves into the strengths and limitations of this specific delivery route by considering the anatomical complexities and influential factors that play a role during dosing. Furthermore, this study introduces strategic approaches for incorporating nanoparticles and ISG delivery within the framework of intranasal applications. Finally, the review provides recent information on approved products and the clinical trial status of products related to intranasal administration, along with the inclusion of quality-by-design-related insights.
Topics: Administration, Intranasal; Blood-Brain Barrier; Brain; Drug Delivery Systems; Lipids; Liposomes; Nanoparticles; Nasal Mucosa
PubMed: 38414526
DOI: 10.2147/IJN.S439181