Olfactory capacity declines with aging, but increasing evidence shows that smell dysfunction is one of the early signs of prodromal neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. The study of olfactory ability and its role in neurodegenerative diseases arouses much interest in the scientific community. In neurology, olfactory impairment is a potential early marker for the onset of neurodegenerative diseases, but the underlying mechanism is poorly understood. The loss of smell is considered a clinical sign of early-stage disease and a marker of the disease’s progression and cognitive impairment. Highlighting the importance of biological bases of smell and molecular pathways could be fundamental to improve neuroprotective and therapeutic strategies. We focused on the review articles and meta-analyses on olfactory and cognitive impairment. We depicted the neurobiology of olfaction and the most common olfactory tests in neurodegenerative diseases. In addition, we underlined the close relationship between the olfactory and cognitive deficit due to nasal neuroepithelium, which is a direct extension of the CNS in communication with the external environment. Neurons, Nose, and Neurodegenerative diseases highlights the role of olfactory dysfunction as a clinical marker for early stages of neurodegenerative diseases when it is associated with molecular, clinical, and neuropathological correlations.

Obstructive sleep apnea syndrome (OSAS) is characterized by intermittent hypoxia (IH) during sleep due to recurrent upper airway obstruction. The derived oxidative stress (OS) leads to complications that do not only concern the sleep-wake rhythm but also systemic dysfunctions. The aim of this narrative literature review is to investigate molecular alterations, diagnostic markers, and potential medical therapies for OSAS. We analyzed the literature and synthesized the evidence collected. IH increases oxygen free radicals (ROS) and reduces antioxidant capacities. OS and metabolic alterations lead OSAS patients to undergo endothelial dysfunction, osteoporosis, systemic inflammation, increased cardiovascular risk, pulmonary remodeling, and neurological alterations. We treated molecular alterations known to date as useful for understanding the pathogenetic mechanisms and for their potential application as diagnostic markers. The most promising pharmacological therapies are those based on N-acetylcysteine (NAC), Vitamin C, Leptin, Dronabinol, or Atomoxetine + Oxybutynin, but all require further experimentation. CPAP remains the approved therapy capable of reversing most of the known molecular alterations; future drugs may be useful in treating the remaining dysfunctions.

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.

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.

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.