Post-COVID-19 Hyposmia Does Not Exhibit Main Neurodegeneration Markers in the Olfactory Pathway.

The biological substrate of persistent post-COVID-19 hyposmia is still unclear. However, as many neurodegenerative diseases present with smell impairment at onset, it may theoretically reflect degeneration within the central olfactory circuits. However, no data still exist regarding the post-COVID-19 patients. As the olfactory neurons (ONs) mirror pathological changes in the brain, allowing for tracking the underlying molecular events, here, we performed a broad analysis of ONs from patients with persistent post-COVID-19 OD to identify traces of potential neurodegeneration. ONs were collected through the non-invasive brushing of the olfactory mucosa from ten patients with persistent post-COVID-19 hyposmia (lasting > 6 months after infection) and ten age/sex-matched controls. Immunofluorescence staining for protein quantification and RT-PCR for gene expression levels were combined to measure ONs markers of α-synuclein, amyloid-ß, and tau pathology, axonal injury, and mitochondrial network. Patients and controls had similar ONs levels of oligomeric α-synuclein, amyloid-ß peptide, tau protein, neurofilament light chain (NfL), cytochrome C oxidase subunit 3 (COX3), and the heat shock protein 60 (HSP60). Our findings thus did not provide evidence for synucleinopathy and amyloid-ß mismetabolism or gross traces of neuronal injury and mitochondrial dysfunction within the olfactory system in the early phase of persistent post-COVID-19 hyposmia.

Angioleiomyoma of the Sinonasal Tract: A Systematic Review of an Uncommon Clinicopathological Entity.

Introduction Angioleiomyoma is a rare neoplasm that represents ∼ 0.2 % of all head and neck benign tumors and ∼ 2% of total cases of tumors of the sinonasal tract. It was once considered a possible subtype of leiomyoma, but, in the 2020 World Health Organization (WHO) classification of soft tissue tumors, it is accepted as a singular entity. Objective To systematically review the existing literature on angioleiomyoma in the light of the new classification of soft tissue tumors. Data Synthesis The present study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A comprehensive search in the PubMed, Cochrane, Scopus, and Google Scholar databases was performed in January 2022. The search items included the following keywords: nasal angioleiomyoma OR sinonasal angioleiomyoma OR nasal vascular leiomyoma OR sinonasal vascular leiomyoma . A total of 87 patients were evaluated. He age of the patients in the studies ranged from 15 to 88 years (mean age at diagnosis: 55.6 years). The most common site of involvement was the nasal septum (28.4 %), followed by the inferior turbinate (22.5%). The most common symptom was nasal obstruction (66.7%), followed by epistaxis (47.1%). Surgical excision represented the main treatment, and there was recurrence of pathology in only 1 case (0.9%). Conclusion To our knowledge, only 87 cases of sinonasal-tract angioleiomyoma have been previously described. The results of the present review seem to confirm the rarity and the benign nature of this neoplasm, and they seem to confirm the necessity to improve the available data about sinonasal-tract angioleiomyoma.

Refractory Pseudomonas Osteomyelitis of the Skull Base With Gradenigo's Syndrome: Early Dysphagia and Late Abducens Nerve Palsy.

Gradenigo's syndrome (GS) is a rare entity characterized by otitis media, pain in the trigeminal nerve distribution and abducens nerve palsy. The classic triad is uncommon, making the diagnostic workup challenging. Specifically, the diagnostic approach includes medical history, a complete otorhinolaryngological examination, a pure-tone audiogram and radiological investigation such as contrast-enhanced computed tomography scan and magnetic resonance imaging of head and neck. Broad-spectrum antibiotics are the first-line treatment, such as intravenous (IV) ceftriaxone and IV metronidazole. Here, we present the case of a 71-year-old man with a previous history of otitis media and poorly controlled type 2 diabetes mellitus. He presented to our attention with facial pain, left hemilarynx paralysis, dysphagia and otorrhea. The patient was treated with broad-spectrum antibiotics without any clinical improvement. Imaging evaluations demonstrated the presence of wide and poorly defined pathological material with epicenter in the masticatory space, involving all nearby structures. The patient underwent multiple biopsies without obtaining a definitive tissue diagnosis of neoplasia. After 2 months, the patient developed delayed VI cranial nerve palsy, providing evidence of GS. Although incomplete, GS has been described in the literature; however, none of the cases exhibited a latent abducent deficit. To the best of our knowledge, this is the only case with a delayed onset of abducens nerve palsy.

Assessing Cognitive Effort in Ménière's Disease: Pupillometry as a Novel Tool for Postural Control.

BACKGROUND: This study aimed to investigate the utility of pupillometry as a measure of cognitive effort in individuals with Ménière's disease experiencing chronic postural destabilization. By integrating pupillometry with static posturography, we sought to gain deeper insights into the cognitive demands and arousal levels associated with postural control in this specific patient population. METHODS: The study included 36 patients who met the diagnostic criteria for Ménière's disease and a control group comprising 36 healthy volunteers. We performed static posturography using a computerized static posturography platform to objectively assess postural imbalance. Additionally, pupillometry was recorded using infrared video-oculoscopy. Pupil dilation was measured before and after participants walked for 7 steps on-site with their vision obscured. RESULTS: Baseline tonic pupil size showed no significant difference between healthy controls and Ménière's patients. However, after walking stimulation, Ménière's patients exhibited highly significant abnormal walking-induced pupil dilation. This suggests increased arousal in response to the challenging task of walking with closed eyes, linked to static upright stance imbalance as correlated with posturography parameters. CONCLUSION: Pupillometry holds promise as an objective tool to assess cognitive effort and arousal during postural control in Ménière's disease. Implementing pupillometry in clinical practice could enhance the management of postural instability in these patients. Our findings contribute to the understanding of cognitive aspects in balance control and open new avenues for further investigations in vestibular dysfunction.

Autoantibody profiles assessment in individuals with persistent olfactory impairment following SARS-CoV-2 infection.

BACKGROUND: Olfactory impairment, particularly hyposmia and anosmia, has emerged as a distinctive early symptom of SARS-CoV-2. Drawing on the historical association of autoimmune diseases with olfactory function, this study delves into the connections between COVID-19, autoimmunity, and persistent olfactory dysfunctions, focusing on individuals experiencing long-lasting smell disorders (3-18 months post-SARS-CoV-2 infection). METHODS: The study comprised 36 Long Covid patients with persistent olfactory dysfunctions, alongside two control groups. Olfactory functionality was assessed using the Sniffin' Sticks extended test. Non-invasive olfactory mucosa brushing and nasal secretions were processed for nasal samples, while serum samples were obtained through peripheral venous sampling. A panel of autoantibodies, including Immunocirculating Complexes, ANA, ENA, and AECA, was investigated in serum and brush supernatant samples. RESULTS: Contrary to expectations, the absence of traditional autoantibodies challenges the proposed autoimmune etiology of Long Covid-associated olfactory dysfunction. However, the presence and potential pathogenic role of AECA suggest viral cytopathic and inflammatory involvement in specific anatomical districts. One hypothesis explores the impact of inflammation and cytokine release induced by the viral infection, altering neuronal signaling and contributing to persistent hyposmia. CONCLUSION: This research contributes to our understanding of the complex relationships between autoimmunity, olfactory impairment, and COVID-19. The absence of classical autoantibodies challenges prevailing theories, while the prominence of AECA hints at unique viral-induced pathogenic mechanisms. By unraveling these complexities, this study enhances our comprehension of post-acute sequelae, offering valuable perspectives on immune-mediated responses in the aftermath of the pandemic.

Biologics in severe uncontrolled chronic rhinosinusitis with nasal polyps: A bicentric experience.

BACKGROUND AND AIM: The introduction of biologics in the management of chronic rhinosinusitis with nasal polyposis (CRSwNP) has allowed new therapeutic options and Dupilumab represents the first approved biological agent. Aim of this paper is to provide a multicentric study in a real-life setting of treatment with Dupilumab for severe uncontrolled CRSwNP in Italy. METHODS: A retrospective data collection was performed from the departments of Otolaryngology of two major health institutions in Rome: San Camillo Forlanini Hospital and Tor Vergata University. Both centres contributed to the study providing information about patients affected by severe uncontrolled CRSwNP and treated with Dupilumab. RESULTS: A total of 83 patients were included in the study (43 males; 40 females; mean age: 55.8 years). Monitoring our patients, we observed improvement in reduction of nasal polyposis and nasal obstruction, respectively measured through NPS and PNIF. Concerning the CRSwNP symptoms and their impact on quality of life, we found an improvement in the olfaction, as measured respectively by SSIT-16 and SNOT-22. CONCLUSIONS: Dupilumab has demonstrated broad efficacy in CRSwNP management. Further studies are needed to confirm our results and to establish biomarkers to identify endotypes and predict response to biologics treatment in CRSwNP.

Transnasal Endoscopic Treatment of Tension Pneumocephalus Caused by Posttraumatic or Iatrogenic Ethmoidal Damage.

Background: Tension pneumocephalus is a neurosurgical emergency caused by progressive accumulation of air in the intracranial spaces mediated by a valve mechanism. Tension pneumocephalus usually presents with headaches, reduced consciousness, and even death. One of the most common causes is an ethmoidal defect resulted by nasal surgery or facial traumas. Methods: A literature review about tension pneumocephalus resulting from ethmoidal damages was performed. Surgery strategies included decompression by frontal burr holes and multilayer repair of the ethmoidal defect. In this paper, an endoscopic technique that exploits the ethmoidal defect to decompress the intracranial spaces and to resolve tension pneumocephalus with fewer complications and shorter hospitalization in comparison to frontal craniotomy is proposed. Conclusion: The proposed endonasal endoscopic technique could be effectively used as a first-line treatment for symptomatic tension pneumocephalus caused by posttraumatic or iatrogenic ethmoidal defect.

Hearing and Ageing.

Age-related hearing loss (ARHL), or presbycusis, occurs in most mammals, humans included, with a different age of onset and magnitude of loss. It is associated with two major symptoms: loss of sensitivity to sound, especially for high pitches, and a reduced ability to understand speech in background noise. This phenomenon involves both the peripheral structures of the inner ear and the central acoustic pathways. Several mechanisms have been identified as pro-ageing in the human cochlea. The main one is the oxidative stress. The inner ear physiological degeneration can be affected by both intrinsic conditions, such as genetic predisposition, and extrinsic ones, such as noise exposure. The magnitude of neuronal loss precedes and exceeds that of inner hair cell loss, which is also less important than the loss of outer hair cells. Patients with HL often develop atrophy of the temporal lobe (auditory cortex) and brain gliosis can contribute to the development of a central hearing loss. The presence of white matter hyperintensities (WMHs) on the MRI, which is radiologic representation of brain gliosis, can justify a central HL due to demyelination in the superior auditory pathways. Recently, the presence of WMHs has been correlated with the inability to correctly understand words in elderly with normal auditory thresholds.

Correction: Guerrieri et al. Nasal and Salivary Mucosal Humoral Immune Response Elicited by mRNA BNT162b2 COVID-19 Vaccine Compared to SARS-CoV-2 Natural Infection. Vaccines 2021, 9, 1499.

The authors wish to make the following corrections to this paper [...].

Substance P and Prokineticin-2 are overexpressed in olfactory neurons and play differential roles in persons with persistent post-COVID-19 olfactory dysfunction.

Persistent olfactory dysfunction (OD) is one of the most complaining and worrying complications of long COVID-19 because of the potential long-term neurological consequences. While causes of OD in the acute phases of the SARS-CoV-2 infection have been figured out, reasons for persistent OD are still unclear. Here we investigated the activity of two inflammatory pathways tightly linked with olfaction pathophysiology, namely Substance P (SP) and Prokineticin-2 (PK2), directly within the olfactory neurons (ONs) of patients to understand mechanisms of persistent post-COVID-19 OD. ONs were collected by non-invasive brushing from ten patients with persistent post-COVID-19 OD and ten healthy controls. Gene expression levels of SP, Neurokinin receptor 1, Interleukin-1ß (IL-1ß), PK2, PK2 receptors type 1 and 2, and Prokineticin-2-long peptide were measured in ONs by Real Time-PCR in both the groups, and correlated with residual olfaction. Immunofluorescence staining was also performed to quantify SP and PK2 proteins. OD patients, compared to controls, exhibited increased levels of both SP and PK2 in ONs, the latter proportional to residual olfaction. This work provided unprecedented, preliminary evidence that both SP and PK2 pathways may have a role in persistent post-COVID-19 OD. Namely, if the sustained activation of SP, lasting months after infection's resolution, might foster chronic inflammation and contribute to hyposmia, the PK2 expression could instead support the smell recovery.

Olfactory Neuron Prokineticin-2 as a Potential Target in Parkinson's Disease.

OBJECTIVE: The objective of this study was to outline the dynamics of prokineticin-2 pathway in relation to clinical-pathological features of Parkinson's disease by examining olfactory neurons of patients. METHODS: Thirty-eight patients (26 de novo, newly diagnosed) and 31 sex/age-matched healthy controls underwent noninvasive mucosa brushing for olfactory neurons collection, and standard clinical assessment. Gene expression levels of prokineticin-2, prokineticin-2 receptors type 1 and 2, and prokineticin-2-long peptide were measured in olfactory neurons by real-time polymerase chain reaction (PCR); moreover, the prokineticin-2 protein and α-synuclein species (total and oligomeric) were quantified by immunofluorescence staining. RESULTS: Prokineticin-2 expression was significantly increased in Parkinson's disease. De novo patients had higher prokineticin-2 levels, directly correlated with Movement Disorder Society-Sponsored Revision of the Unified Parkinson Disease Rating Scale (MDS-UPDRS) part III motor score. In addition, oligomeric α-synuclein was higher in Parkinson's disease and directly correlated with prokineticin-2 protein levels. Total α-synuclein did not differ between patients and controls. INTERPRETATION: Prokineticin-2 is a chemokine showing neuroprotective effects in experimental models of Parkinson's disease, but translational proof of its role in patients is still lacking. Here, we used olfactory neurons as the ideal tissue to analyze molecular stages of neurodegeneration in vivo, providing unprecedented evidence that the prokineticin-2 pathway is activated in patients with Parkinson's disease. Specifically, prokineticin-2 expression in olfactory neurons was higher at early disease stages, proportional to motor severity, and associated with oligomeric α-synuclein accumulation. These data, consistently with preclinical findings, support prokineticin-2 as a candidate target in Parkinson's disease, and validate reliability of olfactory neurons to reflect pathological changes of the disease. ANN NEUROL 2023;93:196-204.

Evaluation of the accuracy in the mucosal detection of anti-SARS-CoV-2 antibodies in nasal secretions and saliva.

COVID-19 vaccination with mRNA vaccines induces immune responses capable of neutralizing SARS-CoV-2. Commercially available serological anti-SARS-CoV-2 quantitative and neutralizing assays are essential for the determination of immune responses to vaccines. Nevertheless, at present there is a lack of validated tests to assess the mucosal response to COVID-19 vaccination and standardized analytic and pre-analytic methods have not yet been defined. The aim of our study was to evaluate the accuracy of two diagnostic immunoassays for COVID-19 (ELISA for IgA-S1 and chemiluminescent assay for IgG-RBD) on serum, saliva, and nasal secretions, by the enrollment of three study populations (healthy controls, vaccinated subjects, and subjects recovered from COVID-19 infection). In order to obtain an appropriate cut-off value for the biological matrices studied, ROC curve analyses were performed. Data demonstrate that the analytical and pre-analytical method we have developed can provide accurate and reliable results for the detection of anti-SARS-CoV-2 mucosal specific antibodies (IgA-S1 and IgG-RBD) on saliva and, as a novelty, on nasal secretions, either after COVID-19 infection or in vaccinated subjects.

Deep learning and machine learning-based voice analysis for the detection of COVID-19: A proposal and comparison of architectures.

Alongside the currently used nasal swab testing, the COVID-19 pandemic situation would gain noticeable advantages from low-cost tests that are available at any-time, anywhere, at a large-scale, and with real time answers. A novel approach for COVID-19 assessment is adopted here, discriminating negative subjects versus positive or recovered subjects. The scope is to identify potential discriminating features, highlight mid and short-term effects of COVID on the voice and compare two custom algorithms. A pool of 310 subjects took part in the study; recordings were collected in a low-noise, controlled setting employing three different vocal tasks. Binary classifications followed, using two different custom algorithms. The first was based on the coupling of boosting and bagging, with an AdaBoost classifier using Random Forest learners. A feature selection process was employed for the training, identifying a subset of features acting as clinically relevant biomarkers. The other approach was centered on two custom CNN architectures applied to mel-Spectrograms, with a custom knowledge-based data augmentation. Performances, evaluated on an independent test set, were comparable: Adaboost and CNN differentiated COVID-19 positive from negative with accuracies of 100% and 95% respectively, and recovered from negative individuals with accuracies of 86.1% and 75% respectively. This study highlights the possibility to identify COVID-19 positive subjects, foreseeing a tool for on-site screening, while also considering recovered subjects and the effects of COVID-19 on the voice. The two proposed novel architectures allow for the identification of biomarkers and demonstrate the ongoing relevance of traditional ML versus deep learning in speech analysis.

Improvement of Psoriasis Using Oral Probiotic Streptococcus salivarius K-12: a Case-Control 24-Month Longitudinal Study.

Psoriasis is a common chronic skin disease, associated with an important physical and physiological involvement for any age. There is a strong link between psoriasis and streptococcal infection, particularly that of the tonsils. There are many therapies to treat psoriasis including topical, systemic, and biologic agents but these treatments are not free from side effects. Streptococcus salivarius K-12 is an oral probiotic product useful for the prophylaxis and treatment of tonsillar infections in children and adults, now tested here for the first time for control of psoriasis. Our retrospective analysis was conducted on 198 patients affected by mild to moderate psoriasis: 100 patients were first treated for 90 days with Streptococcus salivarius K-12, while 98 did not receive any probiotics and were the control group. The patients treated with S. salivarius K-12 exhibited a significant improvement of their psoriasis from the baseline condition: 83.7% patients treated achieved a 100% improvement of the PASI score at 24 weeks and efficacy continued to improve with longer treatment, maintaining same result also during follow-up observation. In all patients, the treatment was well tolerated, and no adverse events have been observed. Our data show that oral preparations containing Streptococcus salivarius may provide a beneficial option for the prevention and cure of pediatric and adult psoriasis.

Odontogenic Maxillary Sinusopathies: a Radiological Classification.

Purpose: Before implant surgery, a preoperative radiological evaluation is recommended for recognizing maxillary inflammatory conditions. In order to avoid a failure of the dental procedure and prevent medical-legal consequences, it is necessary to treat patients suffering of maxillary sinus pathologies. The classification proposed in our study aims to standardize the reference values for mucosal thickening and to verify their association with the odontogenic or disventilatory causes of sinus pathology. Methods: The maximum mucosal thickness was measured at the level of the maxillary sinus floor: mucosal thickness was present when greater than 1 mm and was classified according to its extension within the sinus cavity. Results: Imaging data of 270 adult patients were included, performed for dental diagnosis and treatment planning, and they were divided into four main classes: Class I (85 pt.), mucosal thickness lesser than 2 mm, not pathological. Class II A (52 pt.), mucosal thickness between 2 and 5 mm, localized to the maxillary sinus floor: it is still considered non-pathological, and a "wait-and-see" approach is recommended. Class II B (46 pt.), mucosal thickness greater than 5 mm but localized at sinus floor: pathological mucosa with odontogenic etiology, requiring dental treatment. Class III A (39 pt.), mucosa thicker than 5 mm and concentric, most likely due to sinus ventilation disfunction: it requires maxillary antrostomy. Class III B (30 pt.), sinonasal manifestations such as nasal polyposis, retention cysts, mucocele, dental foreign body: pathological mucosa to be treated with ESS. Class IV (12 pt.), oroantral fistula: nasal endoscopic or oral approach. Conclusions: Our classification intends to suggest the better therapeutic option, in case of sinus pathology, according to the entity and pathogenesis of the mucosal thickening, in order to reduce complication and failure rate of dental surgery.

Olfactory Dysfunction, Headache, and Mental Clouding in Adults with Long-COVID-19: What Is the Link between Cognition and Olfaction? A Cross-Sectional Study.

Smell alteration and cognitive impairment are common features of the Long-COVID Syndrome. Mental clouding, often described as brain fog, might affect smell by altering recollection of odors or through a share mechanism of neuroinflammation. We investigated mental clouding, headache, and cognitive function in adult patients with persistent COVID-19 olfactory dysfunction. This multi-center cross-sectional study enrolled 152 adults with self-reported olfactory dysfunction from 3 tertiary centers specialized in COVID-19 olfactory disorders. Inclusion criteria were smell alterations after COVID-19 persisting over 6 months from infection, age >18 and < 65. Exclusion criteria included smell alterations, headache, or memory problems prior to COVID-19 infection. The patients were evaluated by olfactometry, nasal endoscopy, headache scale, cognitive assessment, Mini Mental State Examination (MMSE), and self-reported measures. Smell dysfunction was stratified and classified based on olfactory deficit severity and presence of olfactory distortion (parosmia, cacosmia). Data on smell disorder, mental clouding, MMSE, and headache were analyzed to assess correlations. Among the 152 patients studied, 50 (32.8%) presented with anosmia, 25 (16.4%) with hyposmia, 10 (6.6%) with parosmia/cacosmia, and 58 patients (38.2%) with a combination of hyposmia and parosmia; seven (4.6%) patients suffered from headache exclusively, and two (1.4%) had headache and mental clouding as their primary symptom. Headache was reported by 76 (50%) patients, and mental clouding by 71 (46.7%). The patients reporting headache, mental clouding, or both, had significantly increased risk of suffering from anosmia and/or hyposmia when compared with their counterparts without these neurological symptoms. No patients had reduced MMSE scores. In our cohort of adult patients with post-COVID-19, smell alterations persisting over 6 months, cognitive impairment and headache were associated with more severe olfactory loss, consistent with neuroinflammatory mechanisms mediating a variety of Long-COVID symptoms.