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Introduction: Olfactory dysfunction is a prevalent condition associated with post-viral syndromes, chronic rhinosinusitis, and neurodegenerative diseases. While olfactory cleft sampling has been investigated in neurology, its potential for assessing localized biomarkers in rhinological conditions remains underexplored. This study presents a minimally invasive nasal brushing technique specifically targeting the olfactory cleft, enabling simultaneous biomarker quantification and cytological analysis. A comprehensive literature review was performed to highlight its potential utility in both clinical practice and research., Methods: Nasal brushing was performed under endoscopic guidance in the olfactory cleft using a cytology brush. Samples were processed to quantify localized biomarkers, including calprotectin, circulating immune complexes, and anti-endothelial cell antibodies, among others. Cytological analysis evaluated cellular composition and inflammatory changes. A literature review focused on nasal brushing applications for biomarker collection across rhinology and other fields., Results: This technique allowed precise biomarker analysis specific to the olfactory cleft, demonstrating feasibility and reproducibility. The procedure was well-tolerated, with only minor discomfort and occasional spotting reported. Cytological analysis revealed preserved cellular architecture and inflammatory changes in patients with olfactory dysfunction. Reproducibility testing demonstrated consistent biomarker levels (Spearman correlation 0.9) and stable cytological findings., Conclusion: Olfactory cleft brushing provides a minimally invasive and reproducible approach for assessing localized biomarkers and cytological characteristics in olfactory dysfunction. By focusing on the olfactory cleft, this method offers a targeted tool for advancing the diagnosis and understanding of OD, CRS, and related rhinological conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Septal perforation refers to a defect within the nasal septum, which subsequently creates communication between the two nasal cavities. More than one surgical approach has been described to repair nasal septal perforations; however, they have a high rate of complication. We aim to introduce a new technique of endoscopic repair of septal perforations, which supports the flap and is thus used to prevent commonly encountered complications., Methods: This is a prospective cohort study with 40 patients who underwent thorough clinical examination, including nasal endoscopy, to determine the perforation details. This was followed by computed tomography (CT) scans and blood tests, which were done to exclude granulomatous disease, tumours, base of skull defects, polyps, etc. This new technique uses either a piece of cartilage alone or cartilage combined with a bone to support the flap. In the assessment, the perforation sizes were categorized, and a treatment plan was made for each., Results: The patients in the study were evaluated, and their most common complaint was crusting. Most patients with less than 1 cm perforations did not need support; the majority of those with 1-2 cm perforations required cartilage support, and 2-3 cm perforations required cartilage and bone support., Conclusion: We have proposed a new endoscopic technique that involves using cartilage and bone grafts to support the flaps used for nasal septal perforation repair and reduce the risk of associated complications., Competing Interests: Declarations. Competing interests: The authors have no competing interests to declare that are relevant to the content of this article. Ethics approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the ethics Committee of the University of Sulaimani, College of Medicine. Informed consent: was obtained from all individual participants included in the study. Patients signed informed consent regarding publishing their data and photographs., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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-β, and tau pathology, axonal injury, and mitochondrial network. Patients and controls had similar ONs levels of oligomeric α-synuclein, amyloid-β 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-β mismetabolism or gross traces of neuronal injury and mitochondrial dysfunction within the olfactory system in the early phase of persistent post-COVID-19 hyposmia., (© 2024. The Author(s).)

Background/Objectives : This study aims to explore the potential relationship between unilateral or asymmetric glaucoma and ipsilateral hearing impairment. Methods : In this retrospective study, visual and hearing functions were assessed in patients with unilateral or asymmetric glaucoma. Correlations between retinal nerve fiber layer (RNFL) thickness, visual field mean deviation (MD) values, and pure tone audiometry (PTA) measurements across various frequencies were analyzed to explore potential associations between visual and ipsilateral hearing functions. Differences in PTA values between ears ipsilateral to the more affected glaucomatous eyes and the contralateral ears were studied for statistical significance. Results : Twenty-six patients with unilateral or asymmetric glaucoma were included in the study. Significant differences in hearing thresholds between the ears corresponding to the more severely glaucomatous eyes and the contralateral ears were found at 0.7, 1, 1.5, and 3 kHz ( p < 0.05). Additionally, a statistically significant difference was observed in the speech frequencies (0.5, 0.7, 1, 1.5, 2, 3, and 4 kHz) between ears corresponding to glaucomatous or more affected glaucomatous eyes and the contralateral ears ( p = 0.016). Furthermore, a moderately positive correlation was found between differences in MD and PTA values at 0.125 kHz (r = 0.50; p = 0.01). Conclusions : This study highlights a potential association between unilateral or asymmetric glaucoma and ipsilateral hearing impairment, particularly at speech-relevant frequencies. These findings underscore the importance of integrated sensory assessment in the management of glaucoma patients, suggesting that early detection and intervention for concurrent hearing loss could enhance overall quality of life.

Background: This longitudinal prospective study aims to investigate the potential of circulating calprotectin (cCLP) as a biomarker in persistent olfactory dysfunctions following COVID-19 infection., Methods: Thirty-six patients with persistent hyposmia or anosmia post COVID-19 were enrolled (HT0) and re-evaluated after three months of olfactory training (HT1). Two control groups included 18 subjects without olfactory defects post COVID-19 (CG1) and 18 healthy individuals (CG2). Nasal brushing of the olfactory cleft and blood collection were performed to assess circulating calprotectin levels., Results: Higher calprotectin levels were observed in serum and nasal supernatant of hyposmic patients (HT0) compared to control groups (CG1 and CG2). Post-olfactory training (HT1), olfactory function improved significantly, paralleled by decreased calprotectin levels in serum and nasal samples. Circulating calprotectin holds potential as a biomarker in persistent olfactory dysfunctions after COVID-19. The decrease in calprotectin levels post-olfactory training implies a role in monitoring and evaluating treatment responses., Discussion and Conclusions: These findings contribute to the growing literature on potential biomarkers in post-COVID-19 olfactory dysfunctions and underscore the importance of investigating novel biomarkers for personalized patient management. Nevertheless, further studies are needed to validate the application of calprotectin assay in nasal diseases and its correlation with nasal cytology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This study investigates a novel multimodal treatment for chronic tinnitus, a condition that significantly affects quality of life, by combining personalized sound therapy with both low- and high-frequency electromagnetic wave stimulation. Conducted at Tor Vergata University Hospital in Rome, the research involved 55 patients and employed a portable medical device for therapy delivery. Treatment effectiveness was measured through the Tinnitus Functional Index (TFI), Tinnitus Handicap Inventory (THI), Visual Analogue Scale (VAS), Hyperacusis Questionnaire (HQ), and Short Form-36 Health Survey (SF-36), encompassing initial sound therapy and subsequent multimodal treatment phases. Remarkably, 73% of participants experienced notable improvements in TFI scores, with 39% reporting a significant enhancement of 13 points or more. This improvement was mirrored in secondary outcomes like THI, VAS, and HQ scores, along with certain SF-36 domains, indicating enhanced life quality and reduced tinnitus distress. The study underscored high compliance and no adverse effects, suggesting the combined therapy's promising potential in chronic tinnitus management. The findings advocate for further research to discern the distinct contributions of each treatment modality, positing that this innovative approach could ameliorate tinnitus symptoms and improve patient well-being, confirming its safety and efficacy.

This review discusses available evidence on the mechanisms of action of bacterial lysates, and the clinical effects of their sublingual administration. Bacterial lysates act through many immunological effects, including dendritic cell activation, modification of circulating lymphocyte subsets and antibody production. The production of salivary IgA was repeatedly shown to be induced by the sublingual administration of a prototype bacterial lysate containing soluble and corpuscular antigens. Bacterial lysates are a useful tool for the prevention of recurrent respiratory tract infections. Sublingual administration should be the preferred option., Competing Interests: Disclosure and potential conflicts of interest: GN is the Medical Director of Bruschettini srl, Genova, Italy; GM and FB act as consultant advisors of Bruschettini srl, Genova, Italy; SDG, MDG, MF and GWC have no competing interests. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2024/06/dic.2024-1-5-COI.pdf, (Copyright © 2024 Braido F, Melioli G, Nicolini G, Ferraris M, Di Girolamo S, Di Gioacchino M, Canonica GW.)

The peripheral nervous system can encounter alterations due to exposure to some of the most commonly used anticancer drugs (platinum drugs, taxanes, vinca alkaloids, proteasome inhibitors, thalidomide), the so-called chemotherapy-induced peripheral neurotoxicity (CIPN). CIPN can be long-lasting or even permanent, and it is detrimental for the quality of life of cancer survivors, being associated with persistent disturbances such as sensory loss and neuropathic pain at limb extremities due to a mostly sensory axonal polyneuropathy/neuronopathy. In the state of the art, there is no efficacious preventive/curative treatment for this condition. Among the reasons for this unmet clinical and scientific need, there is an uncomplete knowledge of the pathogenetic mechanisms. Ion channels and transporters are pivotal elements in both the central and peripheral nervous system, and there is a growing body of literature suggesting that they might play a role in CIPN development. In this review, we first describe the biophysical properties of these targets and then report existing data for the involvement of ion channels and transporters in CIPN, thus paving the way for new approaches/druggable targets to cure and/or prevent CIPN.

Introduction: While different methods are employed for fixing narrowed nasal valves and preventing the notching of soft triangles, this study aims to demonstrate the effectiveness of a new technique called Süreyya-Dani Technique., Methods: This prospective study composed 100 patients who underwent rhinoplasty using the Süreyya-Dani technique. All patients presented with either notching of the soft triangle and/or external nasal valve dysfunction. Patients with the absence of soft triangle notching and external nasal valve dysfunction were excluded from this study. Facial analysis was conducted for all patients to identify any asymmetry in the face, and all nasal defects were identified. Descriptive statistics were calculated for different variables. Analytical statistics, namely Chi-Square test, was conducted with a significance level set at P  < 0.05., Results: In the current study, 100 patients were involved, out of which 63 (63%) were female and 37 (37%) were male. The participants' ages ranged from 18 to 46 years, with a mean age of 30 years. various chief complaints were found among patients, with the majority 37(37%) expressing cosmetic concerns. A statistically significant difference was found for the association of nasal tip defects with genders, intraoperative findings, and chef complaints, and the association between the degree of external valve insufficiency and crural weakness ( P -value < 0.05)., Conclusion: Despite many techniques that have been put forward to fix narrowed nasal valves and prevent notching of the soft triangle, the Süreyya-Dani Technique could work to prevent its occurrence successfully., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Omer, Şeneldir, Di Girolamo, Habibullah, Ahmed, Ali, Abdullah, Mustafa, Abdalla, Hassan, Mohammed and Kakamad.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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., Competing Interests: None to declare., (Copyright 2024, Mammarella et al.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

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.

This study investigated the incidence, mortality, and 5-year survival rates of testicular cancers diagnosed in a northern Italian province, which were eventually associated with previous or subsequent extratesticular neoplasms. Cases from 1996 to 2020 were examined by age and histotype (seminoma vs. non-seminoma). The standardized incidence rate was calculated using the European population, and the annual percent change (APC) was reported. The five-year relative survival was estimated using the Pohar Perme method. The association with the second neoplasm was also evaluated. In our study, 385 patients with testicular cancer were included, most of whom were aged between 30 and 40 years. The non-seminoma and seminoma groups accounted for 44% and 18% of younger adults, respectively. The incidence rate increased during the study period (APC 1.6*); however, it increased in seminomas (APC 2.3*) but not in non-seminomas (APC -0.1). Conversely, the mortality rate remained constantly low either overall or in each of the two groups. The overall 5-year survival rate of testicular cancer patients was 95% (99% and 88% for seminomas and non-seminomas, respectively). Primary extratesticular tumors were documented in 37 cases, 18 after and 19 before the testicular cancer diagnosis. Our study confirms that the increased incidence and excellent survival rate are the prerogative of seminomas.

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.

Hormone therapies (HTs) with anti-androgenic properties are a cornerstone for the treatment of prostate cancer (PC) and have significantly improved the survival of patients, though exposing them to a higher risk of cardiovascular diseases (CVDs), which represent a major cause of morbidity and mortality. This occurs due to the high average age of patients undergoing HT for PC, an age group in which CVDs have a high prevalence and incidence, and due to the type and duration of HTs that are increasingly effective but at the same time more aggressive towards cardiovascular health. Recent evidence from the real world suggests, however, that the cardiometabolic risk is widely underestimated and undertreated with significant impact also on the oncological prognosis. In the light of the results of the PRONOUNCE study, in this review it is emphasized the need for a multidisciplinary management of patients with PC who are candidate for or treated with HT by implementing a personalized treatment program in accordance with the current European guidelines on CVD prevention.

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., Competing Interests: Conflict of Interests The authors have no conflict of interests to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit ( https://creativecommons.org/licenses/by/4.0/ ).)

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., Competing Interests: The authors declare that they have no conflicts of interest regarding the publication of this article., (Copyright © 2023 Goran Latif Omer et al.)

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-1β (IL-1β), 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

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., (© 2022 American Neurological Association.)

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., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

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., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Authors Giovanni Costantini, Giovanni Saggio, and Antonio Pisani are advisory members of VoiceWise S.r.l., spin-off company of University of Rome Tor Vergata (Rome, Italy) developing voice analysis solutions for diagnostic purposes; Valerio Cesarini cooperates with VoiceWise and is employed by CloudWise S.r.l., a company developing cloud data storage and software solutions., (© 2022 Elsevier B.V. All rights reserved.)

The aim of this study was to examine the incidence and mortality trends for tumors and cardiovascular disease (CVD) in a province of northern Italy. The study included kidney cancers recorded in the period 1996−2020, divided by sex, age, year of incidence and years from diagnosis. The standardized incidence rate was calculated using the European population, and the Annual Percent Change (APC) was reported. In total, 2331 patients with kidney cancers were identified, mainly males (1504 cases) aged 60−79 years (1240 cases). There were 1257 deaths; there were no differences according sex but there were differences according to age (12.1% among younger adults and 80.4% among 80+). The incidence rate increased in males between 1996 and 2011 (APC = 2.3), while the mortality rate decreased in both males (APC = −3.3%) and females (APC = −4.5%). Comparing the same periods, kidney cancer-specific mortality decreased from 81.8% to 43.7%, while in the same period there was an increasing trend for CVD mortality. Moreover, the risk of CVD mortality increased as we moved away from the diagnosis (from 6.2% to 27.5%, p < 0.01). The same trend was observed for other causes of death (from 12.6% to 32.1%, p < 0.01). Thus, a multidisciplinary approach seems necessary during the follow-up and treatments of patients with kidney cancer.

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., (© 2022. The Author(s).)

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., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Association of Oral and Maxillofacial Surgeons of India 2020.)

Competing Interests: I have no commercial associations, contractual relations, or proprietary considerations that might pose a conflict of interest related or unrelated with the submitted manuscript, and have had no involvements that might raise the question of bias in the work reported or in the conclusions, implications, or opinions stated. The authors disclose no conflicts of interest.

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.