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BackgroundFacial synkinesis (FS) is a distressing sequela of facial palsy (FP) characterized by involuntary, simultaneous movements of facial muscles occurring during voluntary facial expressions. Treatment of synkinesis is challenging, and preventive methods are needed.AimThis study evaluated the efficacy of physical facial nerve rehabilitation (PFNR) therapy alone vs. PNFR with eyelid surgery to correct lagophthalmos and prevent the onset of synkinesis.MethodsTwenty five outpatients were randomized to receive either PFNR alone (neuromuscular retraining and Kabat proprioceptive neuromuscular facilitation) or PNFR and early (90 days after FP onset) eyelid surgery (involving a conservative oculoplastic correction for lagophthalmos with epiphora or ectropion). Comprehensive otolaryngological assessments and Magnetic Resonance Imaging (MRI) were conducted. Synkinesis progression was measured using Another Disease Scale (ADS) at baseline, 3-, 6-, 12-, and 24-months post-treatment. The data were analyzed with ANOVA, τ-test, Chi-Square analyses.ResultsPatients undergoing eyelid surgery with PFNR showed faster (p

The ability to analyze perilymph could allow inner ear pathologies to be studied. However, today, perilymph sampling is only performed for research purposes because of the risk of negative outcomes such as hearing loss or balance disorders. This paper aims to analyze the current literature on perilymph sampling and propose a method to collect perilymph in clinical settings. The published literature on perilymph sampling and its analyses was screened, and the results were analyzed and discussed in this mini review. Also, articles that discussed microneedle technology were reviewed and included in the analysis of the data. Based on the results of this review, we would like to propose a feasible technique to perform perilymph sampling in clinical settings. A total of eight studies analyzing perilymph were identified; data on proteomic, metabolomic and miRNA features present within human perilymph were collected and described. Two articles describing the use and auditory outcomes post microneedle drug injection into the inner ear were identified. Based on the methods for perilymph sampling described in humans and the recent innovations introduced by the use of microneedles, we suggested a feasible method to collect perilymph in the outpatient setting. The analysis of perilymph undoubtedly represents a valid instrument to fully understand inner ear diseases. A combination of traditional and innovative techniques, such as gaining access to the round window through the transcanalar approach using micro-endoscopes and microneedles to perform sampling, might simplify the sampling procedure and make it practicable in a clinical setting.

The purpose of this clinical epidemiological investigation was to examine the oral health conditions of homeless people in the city of Rome, Italy. A total of 157 homeless subjects were subjected to a first dental visit, during which anamnestic information was recorded in a digital medical record. A diagnosis of dental disorders was performed by assessing oral hygiene conditions, periodontal health, the presence of caries and/or root residues, and the presence of partial and/or total edentulousness. Caries and missing teeth were evaluated by the DMFT index. The first major criticality was represented by poor or absent oral hygiene. The examined sample showed a major percentage of high DMFT (63.0%); the most common clinical condition was the presence of numerous root residues. Regarding periodontal health, 73.2% of patients had gingivitis, 21.6% periodontitis, while 11 patients had periodontal pathologies with tooth mobility (7%). Finally, 8.9% of patients had one or two missing elements, 22.9% had partial edentulousness, and 8.9% of the sample had total edentulism. This analysis provides an important basis for strengthening health promotion and the importance of accessible and effective care for this population. It will therefore be necessary to continue to adopt a patient-centered approach geared towards addressing the demands that this population faces in maintaining their oral health.

NGF plays a crucial immunomodulatory role and increased levels are found in numerous tissues during autoimmune states. NGF directly modulates innate and adaptive immune responses of B and T cells and causes the release of neuropeptides and neurotransmitters controlling the immune system activation in inflamed tissues. Evidence suggests that NGF is involved in the pathogenesis of numerous immune diseases including autoimmune thyroiditis, chronic arthritis, multiple sclerosis, systemic lupus erythematosus, mastocytosis, and chronic granulomatous disease. Furthermore, as NGF levels have been linked to disease severity, it could be considered an optimal early biomarker to identify therapeutic approach efficacy. In conclusion, by gaining insights into how these molecules function and which cells they interact with, future studies can devise targeted therapies to address various neurological, immunological, and other disorders more effectively. This knowledge may pave the way for innovative treatments based on NGF manipulation aimed at improving the quality of life for individuals affected by diseases involving neurotrophins.

Recent evidence shows that it is possible to identify the elements responsible for sensorineural hearing loss, such as pro-inflammatory cytokines and macrophages, by performing perilymph sampling. However, current studies have only focused on the diagnosis of such as otologic conditions. Hearing loss is a feature of certain neuroinflammatory disorders such as multiple sclerosis, and sensorineural hearing loss (SNHL) is widely detected in Alzheimer’s disease. Although the environment of the inner ear is highly regulated, there are several communication pathways between the perilymph of the inner ear and cerebrospinal fluid (CSF). Thus, examination of the perilymph may help understand the mechanism behind the hearing loss observed in certain neuroinflammatory and neurodegenerative diseases. Herein, we review the constituents of CSF and perilymph, the anatomy of the inner ear and its connection with the brain. Then, we discuss the relevance of perilymph sampling in neurology. Currently, perilymph sampling is only performed during surgical procedures, but we hypothesize a simplified and low-invasive technique that could allow sampling in a clinical setting with the same ease as performing an intratympanic injection under direct visual check. The use of this modified technique could allow for perilymph sampling in people with hearing loss and neuroinflammatory/neurodegenerative disorders and clarify the relationship between these conditions; in fact, by measuring the concentration of neuroinflammatory and/or neurodegenerative biomarkers and those typically expressed in the inner ear in aging SNHL, it could be possible to understand if SNHL is caused by aging or neuroinflammation.

PurposeThe aim of the present work is to explore the impact of the COVID-19 pandemic on research activities in a vast multidisciplinary academic community to identify the most critical issues.MethodTo this purpose we planned a survey addressed to the entire academic research staff at "Sapienza" University of Rome, which represents the largest Italian academic community. A questionnaire consisting of both open and closed-ended questions was delivered to 4118 individuals in April 2021.ResultsA total of 544 responses were collected. All academic roles were sufficiently represented in the study cohort. The median number of critical issues experienced by academic research staff was three. Among these, the three most frequently reported were related to: "Access to libraries / laboratories / research sites" (21.9%), "Limitation to stay abroad / study / research periods" (17.6%), "Progress of experimental work" (14.7%), with variable prevalence according to academic position and gender. Older subjects reported issues with "Projects' financial reporting" and "Expiration of acquired consumable material more frequently". The most common critical aspects reported in relation to the economic burden were: being "Unable to allocate funds" (31.4%), a "Reduction in clinical and scientific activity" (26.3%) and experiencing "Increased expenses (comprising private costs)" (21.2%) with no differences between genders. Researchers in Applied Sciences and Natural Sciences reported a higher frequency of problems in clinical and scientific activities, whereas increased expenses were reported also by researchers operating in the Humanities field. As a possible solution aimed at improving these issues, most subjects, especially those aged >45 years, indicated "Economic aid" (22.6%), "Reduction in bureaucracy" (19.9%) or "Enhancement of the scientific and clinical activities", whereas those aged ≤45 years felt that an increased duration and better access to PhD programs were to be prioritized.ConclusionOur findings highlight the most critical issues related to research activities during the COVID-19 pandemic in a large academic community. The information achieved may be useful to identify researchers' needs and to design appropriate policies aimed at preparing research institutions for unexpected catastrophic events and limiting the negative impact on academic research activities.

BackgroundHearing can be impaired in many neurological conditions and can even represent a forme fruste of specific disorders. Auditory function can be measured by either subjective or objective tests. Objective tests are more useful in identifying which auditory pathway (superior or inferior) is most affected by disease. The inner ear’s perilymphatic fluid communicates with the cerebrospinal fluid (CSF) via the cochlear aqueduct representing a window from which pathological changes in the contents of the CSF due to brain inflammation could, therefore, spread to and cause inflammation in the inner ear, damaging inner hair cells and leading to hearing impairment identifiable on tests of auditory function.MethodsA systematic review of the literature was performed, searching for papers with case–control studies that analyzed the hearing and migraine function in patients with neuro-inflammatory, neurodegenerative disorders. With data extracted from these papers, the risk of patients with neurological distortion product otoacoustic emission (DPOAE) was then calculated.ResultsPatients with neurological disorders (headache, Parkinson’s disease, and multiple sclerosis) had a higher risk of having peripheral auditory deficits when compared to healthy individuals.ConclusionExisting data lend credence to the hypothesis that inflammatory mediators transmitted via fluid exchange across this communication window, thereby represents a key pathobiological mechanism capable of culminating in hearing disturbances associated with neuroimmunological and neuroinflammatory disorders of the nervous system.

Different types of tissues respond differently to the action of oxidative stress. The visual system is very sensitive to oxidative action due to continuous exposure to light. In consideration of the growing interest of scientific studies towards various compounds endowed with antioxidant and anti-inflammatory properties, we performed a review of the literature focusing on the use of some antioxidant molecules for the treatment of conditions affecting the visual system. In this study, we focused on the ability of two antioxidant agents, the small molecule α-lipoic acid (ALA) and the enzyme superoxide dismutase (SOD), to influence the neurodegenerative physiological processes related to aging and oxidative stress affecting the ocular segment. The literature data report that ALA and SOD can protect against neurodegenerative effects both the optic nerve and retina and, if administered together, they are able to lower the levels of oxidative stress, thus preventing neurodegeneration and reducing the apoptotic process.

Objectives To assess the frequency of loss of smell and taste in children during Covid-19 infection and their prevalence along with other symptoms, as well as the recovery of chemosensory function once healed. Methods To evaluate symptoms during infection, we adapted the Scandinavian adaptation of the Multi-Clinic Smell and Taste Questionnaire and the modified Monel-Jefferson questionnaire. For smell analysis we used Odor Identification (OI) and two variants of the Odor Discrimination (OD) test, and we compared the results with those of a control group. Results We enrolled nine patients in our experimental group and nine in our control group. Fever was the most frequent symptom (55% of cases), followed by anosmia and ageusia (44% of cases), muscle pain and asthenia (22% of cases) and diarrhea, abdominal pain, cough, and headache (11% of cases). In 11% of cases, olfactory symptoms were the only manifestation of the disease. There was no statistically significant difference in OI test and OD tests between the two groups (Children healed from Covid-19 and Control Group). Conclusion Loss of smell and taste are the second most common symptoms of pediatric Covid-19, and they should always be tested because they can be the only manifestations of infection. Olfactory function in Covid-19 children decreases with increasing age and improves with the passage of time after illness.

Several specific groups within the world’s population have shown that they are particularly vulnerable to quality health care problems, differential experiences in the health system or increased burden of ill health [...]

Sudden sensorineural hearing loss (SSHL) affects a patient’s quality of life and requires rapid treatment. The etiology is viral, vascular, and autoimmune, even though, in most cases, it remains idiopathic SSHL. Since 2019, several different complications have been identified following COVID-19 infection. The post-COVID-19 ENT manifestations reported in the literature are sore throat, headache, pharyngeal erythema, nasal obstruction, rhinorrhea, upper respiratory tract infection, and tonsil enlargement. Cases of SSHL, vestibular neuronitis, and audio-vestibular disorders (such as tinnitus, dizziness, and vertigo) have also been reported, albeit in a smaller percentage of patients. We reported our experience of a case of post-COVID-19 SSHL in the absence of any other type of post-COVID symptoms or brain and internal auditory canal magnetic resonance imaging and magnetic resonance angiography modifications. We aimed to identify a serological biomarker of sudden sensorineural hearing loss, and we also dosed and monitored the value of the serum neurofilament light (NfL). the best of our knowledge, this is the first report that associates SSHL and the serological increase in NfL as a potential biomarker of neuronal-disease-related damage.

Abstract Objective First-line therapy for metastatic squamous cell carcinoma of the head and neck (R/M HNSCC) has been revolutionized by the introduction of anti-checkpoint monoclonal antibodies, which have shown a significant improvement in overall survival (OS) gaining approval in a first line setting. Efficacy and safety of first-line weekly chemotherapy, compared to 3-weeks treatment, was retrospectively evaluated in a frail patient population with R/M HNSCC with the aim to evaluate its role as part of a personalized first-line approach. Methods A total of 124 patients with locally incurable R/M HNSCC receiving weekly (21) or three-weekly (103) chemotherapy plus cetuximab in a first line setting from December 2010 to September 2020 were retrospectively reviewed. Treatment outcomes in terms of objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and toxicities were analysed. Results Patients in the three-week subgroup were ECOG PS 0 (39) and 1 (64) while patients in weekly group (21) were all PS 2. No significant differences were reported in terms of age, sex, smoking and previous alcohol abuse considering the two distinct subgroups. Moreover, no statistically significant difference was found in PFS and OS between the two treatment subgroups. The response rate was 35% (36 patients) and 34% (7 patients) in three-week and weekly treatment group, respectively. Seventy patients (68%) in the three-week group experienced chemotherapy-related toxicities, predominantly G3. In the weekly group a predominantly low-grade toxicity was found in a lower number of patients (52%). Conclusion The weekly schedule appears to be an active and safe strategy in frail patients with R/M HNSCC. Based on these data, a weekly schedule could be considered as a first line treatment in all frail patients excluded from pembrolizumab treatment and a study on the combination of weekly chemotherapy and immunotherapy should be performed.

Italy is a natural corridor for entry into Europe, receiving thousands of refugees and migrants needing socio-economic and health assistance yearly. Impaired vision due to eye disease is estimated to affect at least 2.2 billion people worldwide, especially in this underprivileged population. To overcome this deep disparity, new intervention strategies, such as the PROTECT project, were planned with the aim of assessing, in the context of the head–neck area, the eye health in vulnerable applicants and holders of international protection. A total of 3023 migrants were involved in the project. Demographic factors and eye history were collected using a questionnaire. Using portable diagnostic instruments, an eye screening including monocular visual acuity, intraocular pressure, anterior segment, and ocular fundus was performed. The mean age was 31.6 ± 13.1 years and more than 50% underwent the first eye evaluation. Vision impairment was claimed by 16.6% of subjects and the most frequent diseases diagnosed were: refractive errors (11%), strabismus (6%), red eye (6%), cataract (5.3%), and ocular hypertension (1%). Retinal alterations were observed in 5% of migrants. The PROTECT project allows us to increase the accessibility of head–neck disease prevention care. Moreover, our results confirm the utility of an eye screening assessment for early identification of the most relevant and preventable ocular diseases, especially in disadvantaged populations.

Introduction: Arachnoid cyst in the internal auditory canal is a quite rare pathology but due to its compressive action on the nerves in this district should be surgically removed. Several surgical techniques have been proposed but no surgeons have used the minimally assisted endoscope retrosigmoid approach for its removal. Objective: To investigate the feasibility of using a minimally invasive endoscope assisted retro-sigmoid approach for surgical removal of arachnoid cysts in the internal auditory canal. Methods: Minimally invasive endoscope assisted retrosigmoid approach allows to access to the internal auditory canal through a minimally invasive retrosigmoid approach that combines the use of a microscope and an endoscope. It is performed in six steps: soft tissue step, bone step, dura step, cerebellopontine angle step (performed using an endoscope and a microscope), microscope-endoscope assisted arachnoid cysts removal and closure. We tested minimally invasive endoscope assisted retrosigmoid approach for removal of arachnoid cysts in the internal auditory canal on two human cadaveric heads (specimens) of subjects affected from audio-vestibular disorders and with arachnoid cysts in the internal auditory canal confirmed by magnetic resonance imaging. Results: The mass was completely and successfully removed from the two specimens with no damage to the nerves and/or vessels in the surgical area. Conclusion: The results of our study are encouraging and support the feasibility of using minimally invasive endoscope assisted retrosigmoid approach for removal of arachnoid cysts in the internal auditory canal. While further clinical in-vivo studies are needed to confirm the accuracy and safety of using the minimally invasive endoscope assisted retrosigmoid approach for this specific surgery, our group has successfully used the minimally invasive endoscope assisted retrosigmoid approach in the treatment of microvascular compressive syndrome, schwannoma removal and vestibular nerve resection.

Abstract Background Congenital cytomegalovirus (cCMV) infection is the most frequent non-genetic cause of sensorineural hearing-loss (SNHL) (i.e., hearing loss due to a cochlear and/or auditory nerve damage). It is widely accepted that SNHL at birth, when associated to cCMV symptomatic infection involving the central nervous system, benefits from antiviral therapy started in the neonatal period. Conversely, there is no consensus for antiviral treatment in congenitally infected infants diagnosed with isolated SNHL (i.e., SNHL in an otherwise asymptomatic infant) at birth. Our aim was to assess the frequency and the auditory outcome of isolated SNHL at birth due to auditory neuropathy (AN) (i.e., SNHL in a patient with normal cochlear function and auditory nerve dysfunction) in infants with cCMV infection. Methods We retrospectively reviewed the clinical history of 60 infants, born at term, with cCMV asymptomatic infection, without additional risk factors for SNHL, and exhibiting bilateral “pass” otoacustic emissions (OAE). None of them underwent antiviral therapy. Hearing thresholds were assessed by means of Auditory Brainstem Responses (ABR). AN affected children were followed up until possible normalization of the hearing thresholds or definitive diagnosis of AN. Each infant diagnosed with monolateral or bilateral AN was classified according to the worst ear threshold. Results In our population, the first ABR was performed at a mean age of 5.00 ± 2.79 (SD) months and AN was diagnosed in 16/60 (26.67%) infants; in 4 infants the AN was defined as mild (4/4 monolateral), moderate in 11 (5/11 bilateral), and severe in 1 (bilateral). The mean age at first ABR was 3.69 ± 2.80 (SD) months in the 16 babies with AN and 5.48 ± 2.66 (SD) months in the 44 infants with normal hearing (p = 0.007). All AN cases spontaneously recovered a normal auditory threshold over time. The mean length of the audiological follow-up was 32.44 ± 17.58 (SD) months (range 5–60 months). Conclusion A delayed maturation of the auditory pathways should be considered when a mild/moderate isolated AN at birth is detected in cCMV infected infants. Prospective studies conducted on larger populations, and with a longer audiological follow-up, are needed to confirm our findings.

Abstract Hemangiomas are developmental vascular abnormalities that are common in the head and neck (60%), rare in the oral cavity, and uncommon in the tongue. A patient performed a multi‐parametric MRI, which characterized the lesion of his tongue, providing relevant information for diagnostic, therapeutic orientation, and realization of slight aggressive surgery with consequent excellent recovery.

Programmed cell death ligand-1 (PD-L1) binds PD-1 on CD8+ lymphocytes, inhibiting their cytotoxic action. Its aberrant expression by head and neck squamous cell carcinoma (HNSCC) cells leads to immune escape. Pembrolizumab and nivolumab, two humanized monoclonal antibodies against PD-1, have been approved in HNSCC treatment, but ~60% of patients with recurrent or metastatic HNSCC fail to respond to immunotherapy and only 20 to 30% of treated patients have long-term benefits. The purpose of this review is to analyze all the fragmentary evidence present in the literature to identify what future diagnostic markers could be useful for predicting, together with PD-L1 CPS, the response to immunotherapy and its durability. We searched PubMed, Embase, and the Cochrane Register of Controlled Trials and we summarize the evidence collected in this review. We confirmed that PD-L1 CPS is a predictor of response to immunotherapy, but it should be measured across multiple biopsies and repeatedly over time. PD-L2, IFN-γ, EGFR, VEGF, TGF–β, TMB, blood TMB, CD73, TILs, alternative splicing, tumor microenvironment, and some macroscopic and radiological features are promising predictors worthy of further studies. Studies comparing predictors appear to give greater potency to TMB and CXCR9.

Laryngeal adenoid cystic carcinoma (LACC) is a sporadic neoplasm, especially if supraglottic. The COVID-19 pandemic worsened the presenting stage of many cancers and impacted their prognosis negatively. Here, a case of a patient with adenoid cystic carcinoma (ACC) with delayed diagnosis and a rapid deterioration with distant metastasis due to the COVID-19 pandemic is illustrated. Next, we present a literature review of this rare glottic ACC. The COVID-19 pandemic worsened the stage of presentation of many cancers and adversely affected their prognosis. The present case had a rapidly lethal course, undoubtedly due to the diagnosis delay caused by the COVID-19 pandemic, which impacted the prognosis of this rare glottic ACC. Strict follow-up is recommended for any suspicious clinical findings, as an early diagnosis will improve the disease prognosis, and to consider the influence of the COVID-19 pandemic, especially on the timing of common diagnostic and therapeutic procedures for oncological diseases. In the post-COVID-19 era, it is important to generate new diagnostic scenarios to achieve an increasingly rapid diagnosis of oncological diseases, especially the rare ones, through screening or similar procedures.

Introduction: The number of migrants living in Europe is growing rapidly. The PROTECT project is a national study conducted among refugees and migrants in the Lazio region, Italy from February 2018 to September 2021 to evaluate their otolaryngological, dental, and ophthalmic health status. This article reports the results of this study with a special focus on otolaryngological conditions and diseases. Materials and methods: A total of 3023 participants were included in the project. Data on the participants’ demographic factors, migration status, and otolaryngological history were collected using a questionnaire. Each patient underwent clinical ear, nose, and throat examination, and the main otolaryngological conditions and diseases were noted. Results: nearly two-thirds of participants were males (68.1%). The mean age was 31.6 ± 13.1. Most of the participants were born in Nigeria, followed by Bangladesh, Pakistan, Somalia, Mali, and Gambia. The prevalence of chronic noise exposure was 5.2%. Unilateral hearing loss was reported by 6.5% of the subjects, and bilateral hearing loss by 3.6%. The most frequent symptoms reported in the questionnaire were snoring (10.4%), nasal obstruction (5.9%), vertigo (5.0%), otalgia (4.5%), and tinnitus (4.2%). At the clinical examination, the most frequent findings were nasal septum deviation (25.2%), ear wax (6.5%), hypertrophic palatine tonsils (5.3%), and tympanic membrane perforation (1.3%). Conclusions: the PROTECT project allowed for the evaluation of otolaryngological, dental, and ophthalmological conditions in over 3000 migrants, giving them the possibility to access specialist care.

Chronic olfactory dysfunction after SARS-CoV-2 infection occurs in approximately 10% of patients with COVID-19-induced anosmia, and it is a growing public health concern. A regimen of olfactory training and anti-neuroinflammatory therapy with co-ultramicronized palmitoylethanolamide with luteolin (um-PEA-LUT) has shown promising results in clinical trials; however, approximately 15% of treated patients do not achieve full recovery of a normal olfactory threshold, and almost 5% have no recovery. Disease-modifying therapies (DMTs), which are used to treat autoimmune neuroinflammation in multiple sclerosis (MS), have not been studied for treating persistent inflammation in refractory post-COVID-19 smell disorder. This study evaluated COVID-19-related smell loss and MS-related smell loss, comparing the responses to different therapies. Forty patients with MS and 45 reporting post-COVID-19 olfactory disorders were included in the study. All patients underwent nasal endoscopy and were evaluated by using validated Sniffin’ Sticks testing. The patients with long COVID were treated for three months with um-PEA-LUT plus olfactory training. The patients with MS were treated with DMTs. Olfactory functions before and after treatment were analyzed in both groups. At the experimental endpoint, 13 patients in the COVID-19 group treated with um-PEA-LUT had residual olfactory impairment versus 10 patients in the MS group treated with DMTs. The severity of the persistent olfactory loss was lower in the MS group, and the patients with MS treated with IFN-beta and glatiramer acetate had the preservation of olfactory function. These data provide a rationale for considering prospective trials investigating the efficacy of DMTs for post-COVID-19 olfactory disorders that are refractory to um-PEA-LUT with olfactory training. This study is the first to consider the role of DMT in treating refractory post-viral olfactory loss in patients with long COVID.

Head and neck squamous cell carcinoma (HNSCC) arises from the mucosal epithelium in the oral cavity, pharynx, sino-nasal region, and larynx. Laryngeal squamous cell carcinoma (LSCC) represents one-third of all head and neck cancers. Dysregulated RNA-related pathways define an important molecular signature in this aggressive carcinoma. The Survival Motor Neuron (SMN) protein regulates fundamental aspects of the RNA metabolism but, curiously, its role in cancer is virtually unknown. For the first time, here, we focus on the SMN in the cancer context. We conducted a pilot study in a total of 20 patients with LSCC where the SMN was found overexpressed at both the protein and transcript levels. By a cellular model of human laryngeal carcinoma, we demonstrated that the SMN impacts cancer-relevant behaviors and perturbs key players of cell migration, invasion, and adhesion. Furthermore, in LSCC we showed a physical interaction between the SMN and the epidermal growth factor receptor (EGFR), whose overexpression is an important feature in these tumors. This study proposes the SMN protein as a novel therapeutic target in LSSC and likely in the whole spectrum of HNSCC. Overall, we provide the first analysis of the SMN in human cancer.

Introduction: The number of people with migrant status living in Europe is proliferating. Most of the refugees in Italy come from war zones, and many of them denounce having been victims of persecutory acts in their country of origin. Highly cultured migrant populations have shown better results and oral health behaviour than those who were poorly cultured. The PROTECT project aimed to build a network for the early management of head and neck pathologies among refugees and migrants, promoting the dissemination of correct information about the prevention and treatment of these pathologies. Materials and methods: A national cross-sectional study among the refugees and migrant population in the Lazio region, Italy, from February 2018 to September 2021 was performed. The oral health of 3023 participants was investigated within a network of 56 reception centres and cultural associations. Data collected via an oral health survey questionnaire gathered information on participants’ demographic factors, migration status and dental behaviours and clinical examinations of the participants with the help of mouth mirrors, periodontal probes and artificial light. Results: The mean age was 31.6 ± 13.1, and among all the subjects, 2058 were male (68.1%) and 965 were women (41.9%). Most participants were born in Nigeria, followed by Bangladesh, Pakistan, Somalia, Mali and Senegal. The overall oral pain prevalence was 48.2%. The prevalence of patients claiming poor oral hygiene was 32.4%; 36.2% of the subjects consumed high amounts of sugar; and 26.7% saw their dentist for a check-up in the last year. At the clinical examination, 68.9% of patients had caries experience (considering decay of deciduous teeth, and caries of permanent teeth and teeth with fillings), with 32.2% showing pulpal involvement. Low levels of oral hygiene were also found at the clinical examination, with 46.5% of patients presenting plaque and calculus. The trend of the DMFT index was found to be 5.41. Good periodontal health (CPI = 0) was present in approximately 33.5% of patients. The CPI = 1 index reported bleeding from gingivitis in 37% of patients; tartar was found in 27% of patients (CPI = 2). The percentage of patients with CPI = 3 was 3.6%. Just over half (52.2%) of the migrants examined had malocclusion, and only 0.7% had a malocclusion in treatment. Conclusions: The goal to be achieved is to develop education and prevention programs for head–neck diseases, and perhaps even more. The first step towards this goal can be removing the obstacles migrants encounter in accessing health care.

Both physiological and pathological aging processes induce brain alterations especially affecting the speed of processing, working memory, conceptual reasoning and executive functions. Many therapeutic approaches to reduce the impact of brain aging on cognitive functioning have been tested; unfortunately, there are no satisfactory results as a single therapy. As aging is partly contributed by free radical reactions, it has been proposed that exogenous antioxidants could have a positive impact on both aging and its associated manifestations. The aim of this report is to provide a summary and a subsequent review of the literature evidence on the role of antioxidants in preventing and improving cognition in the aging brain. Manipulation of endogenous cellular defense mechanisms through nutritional antioxidants or pharmacological compounds represents an innovative approach to therapeutic intervention in diseases causing brain tissue damage, such as neurodegeneration. Coherently with this notion, antioxidants, especially those derived from the Mediterranean diet such as hydroxytyrosol and resveratrol, seem to be able to delay and modulate the cognitive brain aging processes and decrease the occurrence of its effects on the brain. The potential preventive activity of antioxidants should be evaluated in long-term exposure clinical trials, using preparations with high bioavailability, able to bypass the blood-brain barrier limitation, and that are well standardized.

The role of nasal microbiota in contributing to neuroinflammation is gradually emerging. Multiple sclerosis and chronic rhinosinusitis share important clinical and epidemiological similarities, and the hypothetical connection among these two pathological entities should be carefully investigated. This editorial is based on a review of available literature on this topic. The main international databases were searched using the following keywords: neuroinflammation, nasal microbiota, multiple sclerosis, chronic rhino-sinusal disorders, chronic sinusitis. Four fully-consistent articles that investigated nasal microbiota alteration and/or chronic rhinosinusitis presence in subjects affected by multiple sclerosis were identified. Overall, these studies showed a significant connection between nasal microbiota dysbiosis and the presence of multiple sclerosis. New specific studies to analyze the nasal microbiota and its metabolism in patients affected by multiple sclerosis should be performed. In fact, a series of treatments able to change this flora could improve the rhino-sinusal state with consequent reduction of recurrent episodes of neuro-inflammation.

Background: Three-dimensional (3D) printing has allowed great progression in the medical field. In otolaryngology practice, 3D printing can be used for planning in case of malformation/complex surgery, for surgeon training, and for recreating missing tissues. This systematic review aimed to summarize the current benefits and the possible future application of 3D technologies in the otolaryngology field. Methods: A systematic review of articles that discuss the use of 3D printing in the otolaryngology field was performed. All publications without the restriction of time and that were published by December 2021 in the English language were included. Searches were performed in the PubMed, MEDLINE, Scopus, and Embase databases. Keywords used were: “3D printing”, “bioprinting”, “three-dimensional printing”, “tissue engineering” in combination with the terms: “head and neck surgery”, “head and neck reconstruction”, “otology”, “rhinology”, “laryngology”, and “otolaryngology”. Results: Ninety-one articles were included in this systematic review. The articles describe the clinical application of 3D printing in different fields of otolaryngology, from otology to pediatric otolaryngology. The main uses of 3D printing technology discussed in the articles included in the review were surgical planning in temporal bone malformation, the reconstruction of missing body parts after oncologic surgery, allowing for medical training, and providing better information to patients. Conclusion: The use of 3D printing in otolaryngology practice is constantly growing. However, available evidence is still limited, and further studies are needed to better evaluate the benefits of this technology.

Aberrant expression of the programmed cell death protein ligand 1 (PD-L1) constitutes one of the main immune evasion mechanisms of cancer cells. The approval of drugs against the PD-1-PD-L1 axis has given new impetus to the chemo-therapy of many malignancies. We performed a literature review from 1992 to August 2022, summarizing evidence regarding molecular structures, physiological and pathological roles, mechanisms of PD-L1 overexpression, and immunotherapy evasion. Furthermore, we summarized the studies concerning head and neck squamous cell carcinomas (HNSCC) immunotherapy and the prospects for improving the associated outcomes, such as identifying treatment response biomarkers, new pharmacological combinations, and new molecules. PD-L1 overexpression can occur via four mechanisms: genetic modifications; inflammatory signaling; oncogenic pathways; microRNA or protein-level regulation. Four molecular mechanisms of resistance to immunotherapy have been identified: tumor cell adaptation; changes in T-cell function or proliferation; alterations of the tumor microenvironment; alternative immunological checkpoints. Immunotherapy was indeed shown to be superior to traditional chemotherapy in locally advanced/recurrent/metastatic HNSCC treatments.

Objectives: Asymptomatic carriers account for over a third of all Coronavirus Disease 19 (COVID-19) cases and are characterized by the absence of symptoms but the same infectivity as symptomatic infections. The high percentage of asymptomatic COVID-19 patients is significant in settings with specific vulnerabilities, such as homeless shelters, where the consequences of an outbreak may be dramatic. In this work, we briefly report our experience on residents and staff of homeless shelters in the City of Rome, Italy, with a particular focus on asymptomatic transmission, and compare it with the available evidence. Methods: We performed routine Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) nasopharyngeal swab tests in all residents and staff of homeless shelters managed by the Eleemosynaria Apostolica of the Vatican City State in the city of Rome, Italy, in addition to daily symptom screening, body temperature monitoring, and application of other prevention measures. Results: We evaluated 298 persons and identified twelve positive cases (4%). Most of the positive cases (75%) were asymptomatic, while only three patients reported symptoms that included fever, diarrhea, and cough. Conclusions: Our data confirm the importance of early identification of asymptomatic carriers that could, in vulnerable conditions such as homeless shelters, spread the infection and cause outbreaks with severe consequences on individual and public health.

Background: Oral squamous cell carcinoma (OSCC) is one of the most frequent cancers worldwide. Endoscopic methods may be useful in the evaluation of oral injuries even though the diagnostic gold standard is a biopsy. Targeted screenings could be considered the best way to prevent the occurrence of oral cancer. Aimed to elucidate the potential identification of specific biomarkers of OSCC, the use of saliva is convenient and noninvasive. Many studies reported more than a hundred putative saliva biomarkers for OSCC, and proteogenomic approaches were fundamental to disclosing this issue. Methods: Relevant literature published in the last few years was systematically searched on PubMed and we focused on articles about the use and study of salivary biomarkers in the diagnostics of head and neck cancer (n = 110). Thereafter, we performed a selection focusing on diagnosis with salivary proteomics in OSCC (n = 8). Results: Saliva proteomics can be a source of biomarkers for OSCC. We reviewed literature of biomarker proteins in saliva that could also be evaluated as probable targets for non-invasive screening of oral neoplasm such as cytokines, matrix metalloproteinases, and acute-phase response proteins. Conclusions: The measurement of salivary biomarkers is a highly hopeful technique for the diagnosis of OSCC. Proteogenomic approaches could permit an accurate and early diagnosis of OSCC. This review seeks to generate an up-to-date view on translational OSCC issues by raising awareness of researchers, physicians, and surgeons. Renewed clinical studies, which will validate the sensitivity and specificity of salivary biomarkers, are necessary to translate these results into possible strategies for early diagnosis of OSCC, thus improving patient outcomes.

Infertility is a worldwide health issue defined by the World Health Organization (WHO) as the inability to establish a pregnancy after 12 months or more of regular and unprotected sexual intercourse. Male infertility etiology can be related to either congenital or acquired factors. The therapeutical approach to male infertility depends on the underlying causes and includes medical and surgical treatments. In recent studies, the potential role of nerve growth factor (NGF) in male reproductive physiology has been proposed. It has been hypothesized that neurotrophins might be involved in testis morphogenesis and regulation of several aspects of spermatogenesis. Moreover, it has been shown that NGF exerts its role on gonadotropin-releasing hormone (GnRH) neurons through the activation of the PKC/p–ERK1/2/p–CREB cascade, which leads to the activation of hypothalamic cells and the consequent activation of hypothalamus–pituitary–gonadal axis (HPG) with the secretion of GnRH. Lastly, it has been shown that the physiology of mature sperm is affected by both exogenous and endogenous NGF. The NGF impact on the HPG axis and its effect on GnRH neurons might be exploited in the therapy of male hypogonadism or used as a protective strategy against gonadal dysfunction related to chemotherapeutic agents. Moreover, the improving effect of NGF on sperm motility and vitality could be useful to enhance assisted reproduction outcomes. NGF could be supplemented to cryopreserved sperm samples to counteract the oxidative stress induced by the frozen and thawing processes. Indeed, the potential clinical applications of NGF in male infertility treatment have been discussed.

Vulnerability, as a phenomenon of analysis, has long been the subject of extensive social and economic policy reflections, aimed at planning social welfare interventions to support the areas most exposed to the effects of the economic crisis, especially with reference to the presence of potentially weaker segments of the population [...]

Background and Objectives: Several treatments are available for sudden sensorineural hearing loss (SSNHL), but no studies have compared the different treatments based on the delay from the onset of the disease. Our study aims to compare the effect of hyperbaric oxygen therapy (HBOT), oral steroids (OS) and combination of both therapies (HBOT + OS) for treating SSNHL. Materials and Methods: This randomized study analyzed 171 patients with SSNHL. Patients were evaluated by pure tone audiometry test (PTA) at baseline (T0) and 20 days after treatment (T1). Three groups were available HBOT-A-, OS-B- and HBOT + OS-C-. After baseline PTA, patients were randomly assigned to each group. Statistical analysis was performed by one-way ANOVA and Chi-square. Results: Patients in the HBOT + OS and HBOT groups improved their auditory function (p < 0.05). HBOT was the best choice for treatment when started by 7 days from SSNHL onset, while HBOT + OS in case of late treatment. Profound SNHL recovered equally by HBOT and HBOT + OS (p < 0.05). Upsloping SNHL obtained better auditory results by HBOT compared to HBOT + OS (p < 0.05). Downsloping and flat SSNHL had the most improvement with HBOT + OS compared to HBOT only (p < 0.05). Conclusions: Combination of HBOT and OS is a valid treatment for SSNHL both in case of early and late treatment. Combination of HBOT and OS was the choice with the best results in case of treatment started >14 days from symptom onset.

Patients affected by COVID-19 present a series of different symptoms; despite some of these are common, other less likely appear. Auditory symptoms seem to be less frequent, maybe because rarer or, alternatively, because they are underestimated during the clinical investigation. The hearing impairment might be related to the central or peripheral involvement of the auditory pathways; in particular, the likelihood of thrombosis might be one of the causes. To date, the prevalence of auditory symptoms such as sudden or progressive sensorineural hearing loss and tinnitus is unclear in COVID-19 patients. However, their presence might be an early sign of thrombosis or spread of the infection into the brain. In this systematic review of the literature we investigated the presence of auditory symptoms in COVID-19 patients and discussed their potential origin and causal relationship with SARS-CoV-2. Results showed that, despite rarely, auditory impairment can appear in patients with COVID-19 and should always be investigated for an early treatment and potential indicator of involvement of the central nervous system.

The lingual cyst with respiratory epithelium (LCRE) is a very rare congenital cyst of the tongue, floor of the mouth, pharynx, or hypopharynx with 21 cases reported in the literature [1,2]. Differential diagnosis is very important for patients presenting with lingual cysts, as this may impact treatment and follow-up. The LCRE should be included in the different diagnosis of a dermoid cyst [3], teratoid cyst [4], epidermoid cyst [5], thyroglossal duct cyst [6], lymphoepithelial cyst [7], and mucocele or ranula [8]. Each entity has a peculiar histologic presentation, although the clinical aspect may be very similar [1]. The dermoid cyst is lined by a keratinized squamous epithelium and contains skin appendages in the cyst. The epidermoid cyst is similar to the dermoid cyst but is characterized by non-keratinized squamous epithelium and has a lumen filled with keratin. The teratoid cyst contains derivatives of the endoderm, ectoderm, and/or mesoderm. The thyroglossal duct cyst is usually lined by columnar, stratified squamous epithelium, or an intermediate transition type of epithelium, with the mandatory presence of thyroid tissue in the cyst wall. The lymphoepithelial cyst is identified by the presence of lymphoid aggregates in the cyst wall. A mucous retention cyst, so-called mucocele or ranula, contains mucin and granulation tissue [1]. Read the full text [PDF]

Abstract Epigenetic pathways play a pivotal role in the development and function of the immune system. Over the last decade, a growing body of studies has been published out seeking to explain a correlation between epigenetic modifications and the development of autoimmune disorders. Epigenetic changes, such as DNA methylation, histone modifications, and noncoding RNAs, are involved in the pathogenesis of autoimmune diseases mainly by regulating gene expression. This paper reviews the importance of epigenetic alterations during the development of the most prevalent human autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), Sjogren’s syndrome (SS), autoimmune thyroid diseases (AITD), and type 1 diabetes (T1D), aiming to provide new insights in the pathogenesis of autoimmune diseases and the possibility to develop novel therapeutic approaches targeting the epigenome.

Coronavirus disease 2019 (COVID-19) was declared a pandemic due to its rapid spread worldwide, and its vaccination campaign is considered one of the most historic public hygiene measures in modern medicine. Sudden sensorineural hearing loss (SSHL) is a common emergency that affects patient’s quality of life and requires rapid treatment with steroids. The etiology could be viral or vascular even though in most cases it remains unknown (idiopathic SSHL). During the SARS-CoV-2 vaccination campaign, several rare but serious adverse events have been reported including thrombosis with thrombocytopenia syndrome, myocarditis, and Guillain-Barré Syndrome. ENT adverse events after vaccination were reported too, including cases of sudden sensorineural hearing loss (SSHL), vestibular neuronitis and audio vestibular disorders (such as tinnitus, dizziness, and vertigo). For the first time here, we reported two cases of SSHL after third administration of COVID-19 mRNA vaccine. Even if there is not clear evidence of an association between SSHL and vaccination, adverse effects should be kept in mind since viral infection could be the etiology of SSHL.

Background: Living in socio-economically disadvantaged neighborhoods can predispose persons to numerous health conditions. The purpose of this study was to report the general health conditions of persons living in disadvantaged neighborhoods in Rome, Italy, a large European metropolitan city. Participants were reached through the mobile facilities of the primary care services of the Dicastery for the Charity Services, Vatican City. Methods: People living in disadvantaged neighborhoods were reached with mobile medical units by doctors, nurses, and paramedics. Demographic characteristics, degree of social integration, housing conditions, and history of smoking and/or alcohol use were investigated. Unstructured interviews and general health assessments were performed to investigate common acute and/or chronic diseases, and history of positivity to COVID-19. Basic health parameters were measured; data were collected and analyzed. Results: Over a 10-month period, 436 individuals aged 18–95 years were enrolled in the study. Most lived in dormitories, whereas a few lived in unsheltered settings. Most participants (76%) were unemployed. Smoking and drinking habits were comparable to the general population. The most common pathological conditions were cardiovascular diseases in 103 subjects (23.39%), diabetes in 65 (14.9%), followed by musculoskeletal system disorders (11.7%), eye diseases (10.5%), psychiatric conditions such as anxiety and depression (9.2%), and chronic respiratory conditions (8.7%). Conclusions: Subjects in our sample showed several pathologic conditions that may be related to their living conditions, thus encouraging the development of more efficient and effective strategies for a population-tailored diagnosis and treatment.

Since the COVID-19 outbreak, Italy has been one of the most affected countries in Europe and the second for number of deaths. In this commentary, we discuss some lessons that we learned as health-care providers working in a large public hospital during the pandemic, with a special focus on the importance of infection containment and early diagnosis, the role of swab, serological tests, home isolation and individual protection devices, and the available therapies and management indications to better face a possible new outbreak in the near future. These comments should stimulate a more diffused, efficient, and efficacious management of COVID-19 patients, also reducing the number of admissions to hospital emergency departments and the related spread of the infection.

The United Nations 2030 Agenda for Sustainable Development promotes the “Leaving no one behind” principle and sets goals in areas of critical importance. This principle has become extraordinarily important during the COVID-19 pandemic, and is especially relevant for fragile populations, such as people experiencing homelessness. Homeless persons live in congregate and poor hygiene settings that may favor virus transmission, often have underling physical and mental comorbidities that place them at high risk of severe forms of COVID-19, and have limited access to public healthcare and social services. In addition, the homeless are often overlooked by safety and health monitoring actions. All of these factors, taken together, place homeless persons at high risk of being left behind. It is therefore of utmost importance to put in place adequate public health measures to limit spread of infection among homeless persons, rapidly identify and isolate asymptomatic and minimally symptomatic subjects, promptly and appropriately treat positive cases, and correctly handle the entire socioeconomic environment of vulnerable people.

Background: The development of COVID-19 pandemic has affected all segments of the population; however, it had a significant impact on vulnerable subjects, such as in people experiencing homelessness. The aim of this study was to evaluate the prevalence of COVID-19 spread in homeless persons in the city of Rome, Italy. Design and Methods: Patients included in the study underwent a clinical evaluation and rapid antibody analysis on capillary blood for the presence of immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies to SARS-CoV-2 virus. Symptomatic patients were not included in the screening and immediately referred to local hospitals for further evaluation. Results: One-hundred seventy-three patients of both sexes were tested for SARS-CoV-2 infection through rapid serological test. Age range was 8-80 years; people came from 35 different countries of origin and 4 continents. Test results were negative for most patients (170-98.2%); two patients had positive IgM (1.2%) and one patient had positive IgG (0.6%). Conclusions: Our study is the first to evaluate the prevalence of SARS-CoV-2 infection in people experiencing homelessness in the city of Rome, Italy. Most patients were negative for COVID-19, although several factors may have had an impact on this result, such as the exclusion of symptomatic patients, the limited sensitivity of rapid serological tests in the initial stage of infection and the prevention measures adopted in these populations. Larger studies on fragile populations are needed to prevent and intercept new clusters of infection in the upcoming months.