Persistent COVID-19 parosmia and olfactory loss post olfactory training: randomized clinical trial comparing central and peripheral-acting therapeutics.

PURPOSE: Although COVID-19 anosmia is often transient, patients with persistent olfactory dysfunction (pOD) can experience refractory parosmia and diminished smell. This study evaluated four putative therapies for parosmia in patients with chronic COVID-19 olfactory impairment. METHODS: After screening nasal endoscopy, 85 patients (49 female, 58%) with pOD and treatment-refractory parosmia were randomized to: (1) ultramicronized palmitoylethanolamide and luteolin + olfactory training (OT) (umPEALUT group, n = 17), (2) alpha-lipoic acid + OT (ALA group, n = 21), (3) umPEALUT + ALA + OT (combination group, n = 28), or 4) olfactory training (OT) alone (control group, n = 23). Olfactory function was assessed at baseline (T0) and 6 months (T1) using a parosmia questionnaire and Sniffin' Sticks test of odor threshold, detection, and identification (TDI). Analyses included one-way ANOVA for numeric data and Chi-Square analyses for nominal data on parosmia. RESULTS: The umPEALUT group had the largest improvement in TDI scores (21.8 ± 9.4 to 29.7 ± 7.5) followed by the combination group (19.6 ± 6.29 to 27.5 ± 2.7), both p < 0.01. The control and ALA groups had no significant change. Patients in the combination and umPEALUT groups had significantly improved TDI scores compared to ALA and control groups (p < 0.001). Rates of parosmia resolution after 6 months were reported at 96% for combination, 65% for control, 53% for umPEALUT and 29% for ALA (p < 0.001). All treatment regimens were well-tolerated. CONCLUSIONS: umPEALUT and OT, with or without ALA, was associated with improvement in TDI scores and parosmia, whereas OT alone or OT with ALA were associated with little benefit.

Fresh Frozen Homologous Rib Cartilage: A Narrative Review of a New Trend in Rhinoplasty.

Background: Revision rhinoplasty is a technically demanding surgical procedure that can put every surgeon in trouble. The main issue of these cases is often an altered osteocartilaginous framework following over-resection during the first intervention. Moreover, the available septal or auricular cartilage for grafting is usually not enough. This review aims to examine contemporary advances in applications of fresh frozen cartilage in rhinoplasty. Methods: A structured review of the current literature (up to December 2023) was performed on four bibliographic databases: PubMed, EMBASE, Cochrane and Medline. The search terms were combinations of "Rhinoplasty" and "Cartilage Graft", "Allograft" or "Fresh Frozen Cartilage". The citations of selected studies and review articles were also evaluated if present. Results: The research resulted in 152 articles, and only ten met the inclusion criteria: nine clinical articles and one in vitro study. One of the ten eligible articles was excluded. Conclusions: Fresh frozen rib cartilage proved to be a viable alternative to autologous rib grafts and irradiated homologous rib graft. Despite the higher costs, FFRG can provide a sufficient amount of tissue for grafting avoiding donor site complications and reducing the operative time and proved to have more chondrocytes and to be less prone to resorption compared to irradiated rib.

Modified Valente Technique for Cauliflower Ear: Outcomes in Children at Two-Year Follow-Up : New Surgical Technique for Cauliflower Ear.

BACKGROUND: Cauliflower ear deformity, a common sequela of auricular trauma, presents an esthetic and reconstructive challenge. Existing surgical techniques have limitations, including complexity, donor site morbidity, and variable long-term outcomes. MATERIALS AND METHODS: In this case series, we present a novel and minimally invasive surgical approach for the correction of cauliflower ear deformity that adapts the Valente otoplasty technique; it combines cartilage debulking with helical rim release and Mustardé mattress stitches to restore ear contour and reduce the risk of recurrence. The procedural steps include bielliptic post-auricular skin and soft tissue incision, release of the cartilaginous spring, removal of excess fibrocartilaginous tissue, cartilage reshaping with suture to restore contour, and tissue redistribution to promote adherence of skin to the cartilage framework. RESULTS: Outcomes were evaluated in 7 patients (9 ears) with cauliflower ear deformity, assessing surgical duration, complications, patient satisfaction, and esthetic outcomes at two years after surgery. The mean surgical duration per patient was 52 ± 17 minutes, including 2 bilateral procedures. Follow-up at 24 months showed favorable esthetic outcome in all patients with sustained improvements in auricular contour and symmetry with neither loss of the shape nor recurrence of deformity. Patients reported high satisfaction and improved quality of life, with mean Glasgow Children Benefit Questionnaire scores of 99.3 ± 6.3. CONCLUSIONS: This technique thus demonstrated lasting correction of cauliflower ear with favorable cosmetic outcomes, low risk of complications, and high patient satisfaction. Further investigations and longer-term follow-up are warranted to validate the technique's durability and expand its application to older and more diverse patient populations. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of contents or the online Instructions to Authors www.springer.com/00266 .

Instrumental Assessment and Pharmacological Treatment of Migraine-Related Vertigo in Pediatric Age.

BACKGROUND: The most frequent form of vertigo in pediatric age is represented by vertigo linked to migraine, with a prevalence of 32.7%. This group of pathologies has received a redefinition of the diagnostic criteria to adapt them to the pediatric age with a new classification of the clinical pictures. We have several kinds of problems with these conditions that often have a significant impact on patients' and parents' quality of life: the diagnostic approach involves different tools for the different age groups contained in the pediatric range; the treatment of this type of vertigo is not consolidated due to the limited availability of trials carried out on pediatric patients. Focusing on this topic, the aim of this review was to provide an update on the more recent clinical advances in the diagnosis and treatment of Vestibular Migraine (VM) in children. METHODS: We searched the PubMed, Embase, and Cochrane library databases for articles published in English from January 2015 to April 2023. The secondary search included articles from reference lists, identified by the primary search. Records were first screened by title/abstract, and then full-text articles were retrieved for eligibility evaluation. The searches combined a range of key terms ("Pediatric" AND "Childhood" AND "dizziness" OR "vertigo" AND "vestibular"). RESULTS: Migraine-related vertigo, in its most recent definitions and classifications, is the most frequent group of balance pathologies in pediatric age. The results from the various experiences present in the literature suggest a clinical approach to be integrated with the use of instrumental tests selected according to the age of the patient and the reliability of the results. CONCLUSION: Knowing the timeline of the applicability of vestibular tests and the information that can be obtained from them is fundamental for diagnostic accuracy. Therapy is strongly conditioned by the limited availability of pediatric trials and by the wide range it includes, from very young children to adolescents.

A pilot study to evaluate the expression of microRNA­let­7a in patients with intestinal­type sinonasal adenocarcinoma.

Despite its histological resemblance to colorectal adenocarcinoma, there is little information about the molecular events involved in the pathogenesis of intestinal-type sinonasal adenocarcinoma (ITAC). The present study investigated the possible role and clinical value of microRNA (miR)-let-7a, a head and neck squamous cell carcinoma-related miR, in a well-characterized and homogeneous cohort of patients with ethmoidal ITAC associated with occupational exposure, treated by primary surgery. miR-let-7a expression levels were analyzed in 23 pairs of ethmoidal ITAC and adjacent normal formalin-fixed paraffin-embedded tissues by reverse transcription-quantitative PCR. The expression was evaluated in tumor and healthy tissues according to: Tumor grade (G) of differentiation and extension, and pTNM stage, and presence/absence of recurrence. Comparisons within and between groups were performed using two-tailed Student's paired t-test and one-way ANOVA with Tukey's post hoc test. P<0.05 was considered to indicate a statistically significant difference. miR-let-7a expression in ethmoidal ITAC tissues was significantly lower than that in adjacent normal tissues (P<0.05; mean expression level ± SD, 1.452707±1.4367189 vs. 4.094017±2.7465375). miR expression varied with pT stage. miR-let-7a was downregulated (P<0.05) in advanced stages (pT3-pT4) compared with earlier stages (pT1-pT2). Furthermore, downregulation of miR-let-7a in ITAC was associated with poorly-differentiated (G3) cancer (P<0.05). No other associations were observed between miR-let-7a expression and the other clinicopathological parameters, including disease-free survival. In conclusion, downregulation of miR-let-7a in ITAC was associated with advanced-stage (pT3 and pT4) and poorly-differentiated (G3) disease, suggesting that the mutation of this gene, combined with additional genetic events, could serve a role in ITAC pathogenesis.

Post-operative radiotherapy in adenoid cystic carcinoma of salivary glands versus surgery alone: what is the evidence about survival and local control? A systematic review and meta-analysis.

BACKGROUND: Adenoid cystic carcinoma of the salivary glands is a relatively rare malignancy characterized by slow growth and a poor prognosis, and effective treatments remain challenging to identify. This systematic review, following the PRISMA guidelines, aimed to analyze the potential benefits of post-operative radiotherapy in terms of local control of recurrences and survival advantages when compared with surgery alone in patients with adenoid cystic carcinoma. METHODS: A comprehensive systematic review was conducted by searching the MEDLINE, Cochrane, EMBASE, and OVID databases from January 1999 to July 2022. The goal was to identify articles comparing surgery alone with surgery plus postoperative radiotherapy for adenoid cystic carcinoma of the salivary glands. Downs and Black Checklist was used to assess the methodological quality and risk of bias of each included study. The data analysis was performed using Review Manager version 5.4.1. RESULTS: This review included 8 studies comprising a total of 3103 patients, divided based on the analyzed outcomes. The pooled odds ratio for overall survival at 5 years was 0.87 (95% confidence interval 0.43-1.76, p = 0.70), and at 10 years was 1.23 (95% confidence interval 0.69-2.16, p = 0.48). In both cases, no statistically significant differences were observed. However, the pooled odds ratio for local control at 5 years was 3.37 (95% confidence interval 1.35-8.42, p = 0.009), providing strong support for the use of post-operative radiation. CONCLUSIONS: The findings from the meta-analysis suggest that post-operative radiotherapy significantly improves local control in patients with adenoid cystic carcinoma. However, there was no statistically significant increase in survival at 5 and 10 years. It is essential to note that the quality of the studies included in this meta-analysis ranged from fair to poor. To better clarify the indications for post-operative radiotherapy, future high-quality research is needed, particularly with improved stratification of patient groups. Additionally, it is important to recognize that achieving local control in adenoid cystic carcinoma is crucial for enhancing the overall quality of life for patients. We acknowledge that this review was not registered in the PROSPERO database, and the data pooling was conducted using a random effects model.

Fitostimoline® in fibro-endoscopic and trans-nasal trans-speculum septoplasty as a beneficial tool to improve post-surgical outcome: Preliminary results of a case-control study.

OBJECTIVES: Topic treatment can be useful to improve short and long-term nasal outcomes after nasal surgery, reducing discomfort and risk of synechia. This study aimed at evaluating the effect on clinical outcomes of nasal packaging using Fitostimoline® gauze in FESS and septoplasty. METHODS: A case-control study on hospitalized patients was performed in a tertiary referral center. The control group included 20 patients treated with the standard surgical protocol for septoplasty and standard nasal packaging; treatment group included 21 patients underwent same surgical procedure but in whom the nasal tampon was wrapped with a gauze containing Fitostimoline® before being placed into the nose. RESULTS: Patients in treatment group had better outcomes than control; nasal mucosa showed better healing - recovery of normal color- in those patients in whom we applied the Fitostimoline® gauze around tampons. Moreover, 100 % patients in the treatment group did not refer discomfort during at tampon removal versus 60 % subjects in the control group who referred pain, tension or tearing during the same action. CONCLUSION: Our results, although preliminary because of the small cohort of subjects included, suggest that the apposition of a gauze with Fitostimoline® after nasal surgery might improve the mucosal healing with consequent reduction of patients discomfort during the post-surgical period.

Efficacy and preservation of hearing with low-dose gentamicin in unilateral meniere's disease: A clinical symptomatology-based study.

PURPOSE: Meniere's disease (MD), a disorder of the inner ear, presents numerous therapeutic challenges, and intratympanic (IT) gentamicin has been proposed for intractable cases. However, controversy regarding dosage and method persists. The purpose of this study was to assess the efficacy and safety of low-dose IT gentamicin on vertigo attacks in MD using a clinical symptomatology-based method, wherein administration was repeated only if vertigo attacks recurred, with a 2-week interval between injections. MATERIALS AND METHODS: This study included 88 patients with unilateral intractable MD. All patients received one to five IT injections with 0.5 ml of 10 mg of gentamicin (80 mg/2 ml) with an interval of 2 weeks between injections. Vertigo attacks were evaluated before and after therapy and categorized into classes A-F according to the 2015 Equilibrium Committee criteria. Audiovestibular assessments, including Pure Tone Audiometry and Vestibulo-Ocular Reflex evaluations, were performed. RESULTS: Before treatment, patients had an average of 4.4 vertigo attacks/month; after treatment, this average decreased to 0.52. The majority of patients (57 %) reached Class A or B vertigo control with five or fewer gentamicin injections. VOR gain was slightly affected on the healthy side and significantly reduced on the affected side. No hearing deterioration was found in any of the treated patients. CONCLUSIONS: Low-dose IT gentamicin administration based on clinical symptomatology can produce a satisfactory control of vertigo attacks after treatment. This protocol primarily affected the vestibular function, as demonstrated by the significant reduction in VOR gain on the affected side, while avoiding cochlear damage. The lack of adverse events and preservation of hearing underscore the safety and efficacy of this method. These findings have significant clinical implications, suggesting that a low-dose, clinical symptomatology-based gentamicin treatment regimen could be an effective and safe strategy for managing unilateral Meniere's disease in a larger population.

Enhancing the therapeutic potential of intravenous glycerol for Meniere's disease: Robust results from an extensive patient cohort.

INTRODUCTION: Meniere's disease (MD) is an idiopatic condition characterized by recurrent attacks of vertigo, hearing loss, tinnitus, and aural fullness, affecting quality of life. Intravenous glycerol has shown potential as a therapeutic option. This study evaluates its efficacy in a larger patient cohort. MATERIALS AND METHODS: Retrospective study with 168 patients having unilateral MD unresponsive to dietary restrictions. Intravenous 10 % glycerol with 0.9 % sodium chloride was administered for six months. Audio-vestibular assessments and questionnaires were used. RESULTS: Significant improvements in vertigo control observed. 7.1 % achieved complete control, and 58.3 % had substantial control. Quality of life measures improved, and audiometry thresholds remained unchanged. No major adverse events reported. DISCUSSION: Intravenous glycerol effectively controlled vertigo and improved MD patients' quality of life. Limitations include lack of a control group and a relatively short-term follow-up. Future prospects include randomized controlled trials and optimization of treatment protocols. CONCLUSION: Intravenous glycerol shows promise as a therapeutic option for MD, with notable improvements in vertigo control and quality of life. Further research is needed for validation and optimization.

A Retrospective Multicenter Italian Analysis of Epidemiological, Clinical and Histopathological Features in a Sample of Patients with Acinic Cell Carcinoma of the Parotid Gland.

BACKGROUND: The acinic cell carcinoma (AciCC) of the parotid gland is a rare tumor with an indolent behavior; however, a subgroup of this tumor presents an aggressive behavior with a tendency to recur. The aim of this multicenter study was to identify and stratify those patients with AciCC at high risk of tumor recurrence. METHODS: A retrospective study was carried out involving 77 patients treated with surgery between January 2000 and September 2022, in different Italian referral centers. Data about tumor characteristics and its recurrence were collected. The histological specimens and slides were independently reviewed by a senior pathologist coordinator (L.C.) and the institution's local head and neck pathologist. RESULTS: The patients' age average was 53.6 years, with a female prevalence in the group. The mean follow-up was 67.4 months (1-258, SD 59.39). The five-year overall survival (OS) was 83.2%. The 5-year disease-free survival (DFS) was 60% (95% CI 58.2-61.7). A high incidence of necrosis, extraglandular spread, lymphovascular invasion (LVI), atypical mitosis, and cellular pleomorphism was observed in the high-risk tumors compared to the low-risk ones. CONCLUSION: AciCC generally had an indolent behavior, optimal OS, DFS with few cervical node metastases, and rare distant relapses. This multicenter retrospective case series provides evidence of the need for clinical-epidemiological-histological stratification for patients at risk of poor outcomes. Our results suggest that the correct definition of high-risk AciCC should include tumor size, the presence of necrosis, extraglandular spread, LVI, atypical mitosis, and cellular pleomorphism.

Neuroinflammatory disorders of the brain and inner ear: a systematic review of auditory function in patients with migraine, multiple sclerosis, and neurodegeneration to support the idea of an innovative 'window of discovery'.

Background: Hearing 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. Methods: A 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. Results: Patients with neurological disorders (headache, Parkinson's disease, and multiple sclerosis) had a higher risk of having peripheral auditory deficits when compared to healthy individuals. Conclusion: Existing 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.

Systematic Review of Management and Survival Outcome of Parotid Cancers with Lateral Skull Base Invasion.

Lateral skull base involvement from parotid cancers is a rare condition and is considered a poor prognostic indicator. The aim of this study was to systematically review the literature of parotid tumors with temporal bone invasion to analyze the survival outcome. A systematic literature review was performed in August 2022, without time limits, and 289 patients affected by parotid gland cancers and lateral skull base involvement were included. The most common symptoms in parotid tumors at the onset were indolent mass, facial weakness, pain, and hearing loss; the chi-square value is 23.1063, with a statistically significance (p = < 0.000121). The five most common histologies were adenoid cystic carcinoma, acinic cell carcinoma, mucoepidermoid carcinoma, adenocarcinoma, and squamous cell carcinoma. The facial nerve function after surgery showed statistically significance (functional vs. non-functional; chi-square was 91.7698, p = < 0.00001). Mean follow-up was 36.2 months (range 0.3-192). At the last follow-up, more patients died of disease (DOD; 60/289, 21%) than other causes (DOOC; 5/289, 2%). There is a statistically significant correlation between patients died for tumor (DOD) and patients died for other causes (DOOC) (p = < 0.0001), suggesting that the lateral skull base invasion negatively impacts on survival. Basing on the results of our systematic review, lateral skull base involvement from parotid recurrent/advance tumors should be considered a poor prognostic factor, as the majority of patients die due to this condition. It also would be necessary to have "clear"works, with full data (demographic, clinical, surgical data), and with a longer follow up, in order to assess the best treatment modality of these patients.

Partial Horizontal Supracricoid Laryngectomy: Which Factors Impact on Post-decannulation Swallowing Outcomes? A Prospective Single-Center Experience.

Early decannulation, performed within the first ten days after supracricoid partial laryngectomy, can result in a more rapid recovery of swallowing function with a semisolid bolus in the short term, about 30 days. We selected 20 patients with squamous cell carcinoma of larynx, who underwent supracricoid laryngectomies: 10 cricohyoidopexy (CHP) and 10 cricohyoidoepiglottopexy (CHEP). Staging was pT2 (10 pts), and pT3 (10 pts). Fiberoptic endoscopic evaluation of swallowing was used to assess postoperative swallowing function after a mean of 12 and 22 days from surgery. A modified PAS score (penetration-aspiration scale) was assigned for subtotal laryngectomies. Decannulation occurred after 6.7 ± 2.1 days. Univariate analysis showed that the type of surgery (CHP or CHEP), pT, resection of one arytenoid, and decannulation time are significantly associated with the 12-day PAS score. The 22-day PAS score is significantly associated with only 3 variables: type of surgery, pT, and resection of one arytenoid. From the data presented, the factors that most delay an effective recovery of swallowing are T3 and the resection of one arytenoid. Early decannulation has been shown statistically to improve PAS score in the short term, but not in the long term.

Correlation Between Air-Bone Gap and Vestibular Aqueduct Size in Enlarged Vestibular Aqueduct Syndrome: A Systematic Review.

The purpose of this review was to evaluate the air-bone gap with vestibular aqueduct size in enlarged vestibular aqueduct syndrome. According to the PRISMA guidelines we conducted a systematic review of the literature. Published international articles in English from 2000 to 2022 were screened, checking for studies that evaluated the air-bone gap of patients affected by enlarged vestibular aqueduct syndrome and the size of vestibular aqueduct. Data related to the hearing assessment and imaging investigation of enrolled participants were extracted. The chosen primary outcome measure was the correlation between air-bone-gap and vestibular aqueduct size. The database search allowed us to screen 485 articles and to select 5 articles discussing this topic for a total of 349 patients. Two studies showed a positive correlation between air-bone gap and vestibular aqueduct size, one only a trend and two no correlation. To date, it is not possible to draw conclusions whether or not there is a positive correlation between air-bone gap and vestibular aqueduct size in enlarged vestibular aqueduct syndrome. Higher quality studies would be conducted with standardized outcome measures to clarify the specific research question.

Corrigendum: Auditory disturbances and SARS-CoV-2 infection: brain inflammation or cochlear affection? Systematic review and discussion of potential pathogenesis.

[This corrects the article DOI: 10.3389/fneur.2021.707207.].

Recurrent acinic cell carcinoma of the parotid gland with lateral skull base invasion: Case report and discussion of the literature.

Medical records of a 76-year-old woman with a recurrent acinic cell carcinoma of the left parotid gland with lateral skull base invasion were reviewed. She underwent subtotal petrosectomy followed by radiation therapy. After surgery, she remained disease-free for more than 16 months.

Treatment of COVID-19 olfactory dysfunction with olfactory training, palmitoylethanolamide with luteolin, or combined therapy: a blinded controlled multicenter randomized trial.

PURPOSE: Few evidence-based therapies are available for chronic olfactory dysfunction after COVID-19. This study investigated the relative efficacy of olfactory training alone, co-ultramicronized palmitoylethanolamide with luteolin (um-PEA-LUT, an anti-neuroinflammatory supplement) alone, or combined therapy for treating chronic olfactory dysfunction from COVID-19. METHODS: This double-blinded controlled, placebo-controlled multicenter randomized clinical trial was conducted in 202 patients with persistent COVID-19 olfactory dysfunction of > 6 month duration. After a screening nasal endoscopy, patients were randomized to: (1) olfactory training and placebo; (2) once daily um-PEA-LUT alone; (3) twice daily um-PEA-LUT alone; or (4) combination of once daily um-PEA-LUT with olfactory training. Olfactory testing (Sniffin' Sticks odor identification test) was performed at baseline and at 1, 2, and 3 months. The primary outcome was recovery of over three points on olfactory testing, with outcomes compared at T0, T1, T2 and T3 across groups. Statistical analyses included one-way ANOVA for numeric data and chi-square for nominal data. RESULTS: All patients completed the study, and there were no adverse events. At 90 days, odor identification scores improved by > 3 points in 89.2% of patients receiving combined therapy vs. 36.8% receiving olfactory training with placebo, 40% receiving twice daily um-PEA-LUT alone, and 41.6% receiving once daily um-PEA-LUT alone (p < 0.00001). Patients receiving treatment with um-PEA-LUT alone demonstrated subclinical improvement (< 3 point odor identification improvement) more often than patients receiving olfactory training with placebo (p < 0.0001.) CONCLUSIONS: Olfactory training plus once daily um-PEA-LUT resulted in greater olfactory recovery than either therapy alone in patients with long-term olfactory function due to COVID-19. TRIAL REGISTRATION: 20112020PGFN on clinicaltrials.gov. LEVEL OF EVIDENCE: 1b (Individual Randomized Clinical Trial).

Parosmia COVID-19 Related Treated by a Combination of Olfactory Training and Ultramicronized PEA-LUT: A Prospective Randomized Controlled Trial.

During COVID-19 pandemic, clinicians have had to deal with an ever-increasing number of cases of olfactory disturbances after SARS-CoV-2 infections and in some people this problem persisted for long time after negativization from virus. This a prospective randomized controlled trial aims at evaluating the efficacy of ultramicronized palmitoylethanolamide (PEA) and Luteolin (LUT) (umPEA-LUT) and olfactory training (OT) compared to OT alone for the treatment of smell disorders in Italian post-COVID population. We included patients with smell loss and parosmia who were randomized and assigned to Group 1 (intervention group; daily treatment with umPEA-LUT oral supplement and OT) or Group 2 (control group; daily treatment with placebo and OT). All subjects were treated for 90 consecutive days. The Sniffin' Sticks identification test was used to assess the olfactory functions at the baseline (T0) and the end of the treatment (T1). Patients were queried regarding any perception of altered olfaction (parosmia) or aversive smell, such as cacosmia, gasoline-type smell, or otherwise at the same observational points. This study confirmed the efficacy of combination of umPEA-LUT and olfactory training as treatment of quantitative smell alteration COVID-19 related, but the efficacy of the supplement for parosmia was limited. UmpEA-LUT is useful for the treatment of brain neuro-inflammation (origin of quantity smell disorders) but has limited/no effect on peripheral damage (olfactory nerve, neuro-epithelium) that is responsible of quality disorders.