Publications by authors named "Eugenio De Corso"

66 Publications

Olfaction Recovery following Dupilumab Is Independent of Nasal Polyp Reduction in CRSwNP.

J Pers Med 2022 Jul 26;12(8). Epub 2022 Jul 26.

Otorhinolaryngology, Head and Neck Surgery Unit, Department of Mental and Physical Health and Preventive Medicine, Università degli Studi della Campania Luigi Vanvitelli, 80131 Naples, Italy.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic type 2 inflammatory disease characterized by olfactory impairment (OI) as one of the most troublesome symptoms. Currently, biologics represent a new option in the treatment of uncontrolled type 2 CRSwNP. This is a retrospective real-life observational study involving adult patients affected by severe uncontrolled CRSwNP. At baseline, and 3 and 6 months after Dupilumab add on to intranasal steroids (INS), patients underwent the 22-item Sinonasal Outcome Test (SNOT-22), nasal endoscopy, Visual Analogue Scale (VAS) scale for OI, and Sniffin Sticks-16 items identification test (SS-I). We observed improvement in all clinical outcomes with a significant correlation between VAS-SS-I/SNOT22, whereas we did not find a correlation between Nasal Polyp Score (NPS) and SS-I or VAS. Interestingly, patients reported a higher degree of improvement of OI on the VAS than on the SS-I. These data demonstrate that the patients were not aware about the degree of their OI and the perception of general improvement in their health-related quality of life (HRQoL) may have influenced the VAS score. Moreover, we observed a lack of correlation between NPS and SS-I or VAS, suggesting that OI did not depend on the polyps' volume and may be due mainly to the resolution of inflammation. So, the physiopathological mechanisms underlying OI in CRSwNP and its recovery after Dupilumab might be unrelated to the volume of the polyps and might depend mainly on the anti-inflammatory effects. Future studies including biomarkers may be useful to clarify this aspect.
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http://dx.doi.org/10.3390/jpm12081215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330729PMC
July 2022

Mometasone Furoate in Non-Allergic Rhinitis: A Real-Life Italian Study.

J Pers Med 2022 Jul 20;12(7). Epub 2022 Jul 20.

UOSD Allergologia e Immunologia Clinica, Dipartimento Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.

Background: In order to evaluate the efficacy of intranasal mometasone furoate in patients with non-allergic rhinitis (NAR), a real-life, observational, prospective study is performed.

Methods: Thirty-one patients (age 18-64 years) receive intranasal (mometasone furoate, 200 µg b.i.d. for 15 consecutive days per month for 6 consecutive months), plus isotonic nasal saline. The cytologic pattern of local inflammation, nasal airflow, through peak nasal inspiratory flow (PNIF), quality of life (QoL), through the rhinitis quality of life questionnaire (RQLQ), the sinonasal outcome test (SNOT-22), the short-form 36-item health survey (SF-36v2), and the combined symptom medication score (CSMS), and, finally, olfactory function, through Sniffin' sticks-16 identification test (SSIT-16), are evaluated at baseline and after treatment.

Results: NARNE is the most frequent cytological pattern (48% of the total sample). The therapeutic response shows improvement in olfactory function and QoL.

Conclusions: The results of this study confirm that intranasal mometasone furoate is an effective treatment for patients with NAR.
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http://dx.doi.org/10.3390/jpm12071179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9322075PMC
July 2022

Management of Patients with Severe Asthma and Chronic Rhinosinusitis with Nasal Polyps: A Multidisciplinary Shared Approach.

J Pers Med 2022 Jul 1;12(7). Epub 2022 Jul 1.

Department of Cardiovascular and Thoracic Sciences, Università Cattolica Sacro Cuore, 00168 Rome, Italy.

Chronic rhinosinusitis (CRS) is one of the most frequent comorbidities associated with asthma and it contributes to an amplified global disease burden in asthmatics. CRS prevalence is much higher in asthmatic patients compared to the general population and it is more frequently related to severe asthma, especially in presence of nasal polyps (chronic rhinosinusitis with nasal polyps, CRSwNP). Moreover, asthma exacerbation has a higher occurrence in CRSwNP. From a pathologic point of view, CRS and asthma share similar and connected mechanisms (e.g., type-2 inflammation). A multidisciplinary approach represents a crucial aspect for the optimal management of patients with concomitant asthma and CRSwNP and improvement of patient quality of life. An Italian panel of clinicians with different clinical expertise (pulmonologists, ear, nose and throat specialists, immunologists and allergy physicians) identified three different profiles of patients with coexisting asthma and nasal symptoms and discussed the specific tracks to guide a comprehensive approach to their diagnostic and therapeutic management. Currently available biological agents for the treatment of severe asthma act either on eosinophil-centered signaling network or type-2 inflammation, resulting to be effective also in CRSwNP and representing a valid option for patients with concomitant conditions.
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http://dx.doi.org/10.3390/jpm12071096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320671PMC
July 2022

Calprotectin in nasal secretion: a new biomarker of non-type 2 inflammation in CRSwNP.

Acta Otorhinolaryngol Ital 2022 06 30. Epub 2022 Jun 30.

A. Gemelli Hospital Foundation IRCCS, Unit of Otorhinolaryngology, Head and Neck Surgery, Rome, Italy.

Objective: We analysed calprotectin in sinonasal secretions of different chronic rhinosinusitis with nasal polyps (CRSwNP) endotypes to assess its role as a biomarker of non-type 2 inflammation.

Methods: We included primary diffuse CRSwNP patients (n = 41) and three different control groups [non-allergic rhinitis (NAR) (n = 13), non-allergic eosinophilic syndrome (NARES) (n = 10) and healthy subjects (n = 12)]. Calprotectin levels were detected in nasal secretions using a chemiluminescent immunoassay (CLIA).

Results: Calprotectin levels in nasal secretions were significantly higher in all non-type 2 endotypes of CRSwNP compared to healthy controls (p < 0.05). In contrast, in type-2 CRSwNP calprotectin was significantly lower compared to controls (p < 0.05). A significant correlation between calprotectin levels and neutrophilic count/HPF was found in CRSwNP (p < 0.01). Clinically, mean levels of calprotectin and neutrophilia were significantly higher in patients who previously underwent 3 or more endoscopic sinus surgeries (p < 0.05).

Conclusions: Calprotectin in nasal secretions may be a biomarker of non-type 2 inflammation. Low levels of calprotectin are indicative of a type-2 immune response in both CRSwNP and non-allergic rhinitis. We observed that calprotectin levels significantly increased based on the number of previous surgeries.
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http://dx.doi.org/10.14639/0392-100X-N1800DOI Listing
June 2022

Parathyroid hormone-related peptide and parathyroid hormone-related peptide receptor type 1 in locally advanced laryngeal cancer as prognostic indicators of relapse and survival.

BMC Cancer 2022 Jun 27;22(1):704. Epub 2022 Jun 27.

Formerly Institute of Histology, Università Cattolica del Sacro Cuore, Rome, Italy.

Background: Parathyroid hormone-related peptide (PTHrP) overexpression and poor patient outcome have been reported for many human tumors, but no studies are available in laryngeal cancer. Therefore, we studied the expression of PTHrP and its receptor, parathyroid hormone-related peptide receptor type 1 (PTH1R), in primary locally advanced laryngeal squamous cell carcinomas (LALSCC) also in relation to the clinical outcome of patients.

Methods: We conducted a retrospective exploratory study, using immunohistochemistry, on PTHrP, PTH1R and HER1 expressions in LALSCC of 66 patients treated with bio-radiotherapy with cetuximab.

Results: The expressions of PTHrP and PTH1R in LALSCC were associated with the degree of tumor differentiation (p = 0.01 and 0.04, respectively). Poorly differentiated tumors, with worse prognosis, expressed PTHrP at nuclear level and were PTH1R negative. PTHrP and PTH1R were expressed at cytoplasmic level in normal larynx epithelium and more differentiated laryngeal cancer cells, suggesting an autocrine/paracrine role of PTHrP in squamous cell differentiation of well differentiated tumors with good prognosis. Eighty-one percent HER1 positive tumors expressed PTHrP (p < 0.0001), mainly at nuclear level, consistent with the known up-regulation of PTHrP gene by HER1 signaling. In multivariable analyses, patients with PTHrP positive tumors had a higher relative risk of relapse (HR = 5.49; CI 95% = 1.62-22.24; p = 0.006) and survival (HR = 8.21; CI 95% = 1.19-105.00; p = 0.031) while those with PTH1R positive tumors showed a lower relative risk of relapse (HR = 0.18; CI 95% = 0.04-0.62; p = 0.002) and survival (HR = 0.18; CI 95% = 0.04-0.91; p = 0.029).

Conclusions: In LALSCC nuclear PTHrP and absence of PTH1R expressions could be useful in predicting response and/or resistance to cetuximab in combined therapies, contributing to an aggressive behavior of tumor cells downstream to HER1.
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http://dx.doi.org/10.1186/s12885-022-09748-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9235225PMC
June 2022

Cost-Utility Analysis of Dupilumab for the Treatment of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) in Italy.

J Pers Med 2022 Jun 10;12(6). Epub 2022 Jun 10.

Director Department of Otorhinolaryngology, G. da Saliceto Hospital of Piacenza, 29121 Piacenza, Italy.

The objective of this analysis was to estimate the incremental cost-utility ratio (ICUR) of dupilumab as an add-on treatment to best supportive care (BSC), versus BSC alone, in Italy for severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP). A simulation of outcomes and costs was undertaken using a 1-year decision tree, followed by a lifetime horizon Markov model. Clinical data were derived from a pooled analysis of two studies (SINUS-24 NCT02912468 and SINUS-52 NCT02898454). The Italian National Healthcare Service (NHS) perspective was considered. Model robustness was tested through sensitivity analyses. In the base-case analysis, treatment with dupilumab + BSC resulted in an increase in quality of life-adjusted survival (+1.02 quality-adjusted life years (QALY-gained)), compared to the BSC alone. The resulted ICUR was €21,817 per QALY-gained and it is below the acceptability threshold commonly used in Italy. Both one-way deterministic and probabilistic sensitivity analyses confirmed the robustness of base-case results. The cost-utility analysis showed that dupilumab, as an add-on treatment to BSC, is a cost-effective therapeutic alternative to BSC in the treatment of patients with severe uncontrolled chronic rhinosinusitis with nasal polyps, confirming that it is economically sustainable.
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http://dx.doi.org/10.3390/jpm12060951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9225649PMC
June 2022

The Role of Allergen-Specific Immunotherapy in ENT Diseases: A Systematic Review.

J Pers Med 2022 Jun 9;12(6). Epub 2022 Jun 9.

Unit of Otorhinolaryngology Head and Neck Surgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.

Previous studies have demonstrated that both subcutaneous (SCIT) and sublingual specific immunotherapy (SLIT) are effective in treating allergic rhinitis (AR). Further studies have evaluated the efficacy of allergen-specific immunotherapy (AIT) on different ear, nose, and throat (ENT) manifestations, in which allergy might have an etiopathogenetic role, such as local allergic rhinitis (LAR), rhinosinusitis (RS), otitis media (OM), and adenotonsillar (AT) disease. Nevertheless, the management of allergy in ENT diseases is still debated. To the best of our knowledge, this is the first systematic review assessing the efficacy of AIT in ENT diseases aside from AR. Literature data confirmed that AIT might be an effective therapeutic option in LAR, although its effect is restricted to studies with short-term follow-up. Furthermore, previous research demonstrated that AIT may improve symptoms and surgical outcomes of chronic rhinosinusitis when used as an adjunctive treatment. Few studies supported the hypothesis that AIT may exert positive therapeutic effects on recurrent upper airway infections as adenotonsillar disease. Finally, some clinical observations suggested that AIT may add some benefits in the management of otitis media with effusion (OME). The results of this systematic review allow us to conclude that the efficacy of AIT in ENT disorders has been only slightly investigated and additional studies are needed.
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http://dx.doi.org/10.3390/jpm12060946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9224998PMC
June 2022

Survey on Use of Local and Systemic Corticosteroids in the Management of Chronic Rhinosinusitis with Nasal Polyps: Identification of Unmet Clinical Needs.

J Pers Med 2022 May 29;12(6). Epub 2022 May 29.

Department of Head-Neck and Sensory Organs, Catholic University of Sacred Heart, 00168 Rome, Italy.

: Local and systemic corticosteroids have long been the workhorse in management of chronic rhinosinusitis with nasal polyps (CRSwNP), although there is no universally accepted modality of prescription. We carried out a survey in Italy to capture current trends in the use of topical and systemic corticosteroids in patients with CRSwNP. : A survey was set up on Survey Monkey. Each author distributed the link to the survey in an ad hoc manner and a total of 437 participants filled out the survey. : Mometasone furoate (79.3%) was the most frequently prescribed, administered daily by 61.9% of participants; the remaining preferred to discontinue treatment for brief periods to reduce side effects or to modulate the therapy in mild cases. The majority believe that a short cycle of systemic steroids should be prescribed for re-exacerbation of symptoms and that the number of cycles in the previous year should be evaluated to define control of the disease even if international guidelines do not provide clear indications on this topic. A certain degree of divergence emerged from responses regarding how long and the maximal dose of systemic steroids which place patients at high risk for adverse events. Finally, systemic corticosteroids seem to offer only temporary benefit on recovery of smell without guaranteeing long-term control even if the patient is adherent to topical corticosteroids. : Our results highlight the need for clear guidelines on oral steroids, which could help supporting the use of a precision medicine approach, including indications for new biological agents.
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http://dx.doi.org/10.3390/jpm12060897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9225345PMC
May 2022

Personalized Management of Patients with Chronic Rhinosinusitis with Nasal Polyps in Clinical Practice: A Multidisciplinary Consensus Statement.

J Pers Med 2022 May 23;12(5). Epub 2022 May 23.

Personalized Medicine, Asthma and Allergy-IRCCS Humanitas Research Hospital, 20122 Milan, Italy.

Chronic rhinosinusitis (CRS) is a sino-nasal chronic inflammatory disease, occurring in 5-15% of the general population. CRS with nasal polyps (CRSwNP) is present in up to 30% of the CRS population. One-third of CRSwNP patients suffer from disease that is uncontrolled by current standards of care. Biologics are an emerging treatment option for patients with severe uncontrolled CRSwNP, but their positioning in the treatment algorithm is under discussion. Effective endotyping of CRSwNP patients who could benefit from biologics treatment is required, as suggested by international guidelines. Other issues affecting management include comorbidities, such as allergy, non-steroidal anti-inflammatory drug-exacerbated respiratory disease, and asthma. Therefore, the choice of treatment in CRSwNP patients depends on many factors. A multidisciplinary approach may improve CRSwNP management in patients with comorbidities, but currently there is no shared management model. We summarize the outcomes of a Delphi process involving a multidisciplinary panel of otolaryngologists, pulmonologists, and allergist-immunologists involved in the management of CRSwNP, who attempted to reach consensus on key statements relating to the diagnosis, endotyping, classification and management (including the place of biologics) of CRSwNP patients.
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http://dx.doi.org/10.3390/jpm12050846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9143504PMC
May 2022

Effectiveness of Dupilumab in the Treatment of Patients with Severe Uncontrolled CRSwNP: A "Real-Life" Observational Study in the First Year of Treatment.

J Clin Med 2022 May 10;11(10). Epub 2022 May 10.

Unit of Otorhinolaryngology-Head and Neck Surgery, A. Gemelli Hospital Foundation IRCCS, 00168 Rome, Italy.

The aim of this study was to evaluate the efficacy of dupilumab in the treatment of severe uncontrolled Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), with or without asthma as add-on therapy with intra-nasal corticosteroids in a real-life setting over the first year of treatment. Our data demonstrated that subcutaneous 300 mg dupilumab administered at home via a pre-filled auto-injector every two weeks, based on indications set by the Italian Medicines Agency, was rapidly effective in reducing the size of polyps, decreasing symptoms of disease, improving quality of life, and recovering olfaction. Significant improvement was observed after only 15 days of treatment, and it progressively increased at 6 and 12 months. Dupilumab was also effective in reducing the local nasal eosinophilic infiltrate, in decreasing the need for surgery and/or oral corticosteroids, and in improving control of associated comorbidities such as chronic eosinophilic otitis media and bronchial asthma. After 12 months of treatment, 96.5% of patients had a moderate/excellent response. From our data, it was evident that there was a group of patients that showed a very early response within one month of therapy, another group with early response within six months from baseline, and a last group that improved later within 12 months. The results of this study support the use of dupilumab as an effective option in the current standard of care for patients affected by severe uncontrolled CRSwNP.
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http://dx.doi.org/10.3390/jcm11102684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9146210PMC
May 2022

Update of endoscopic classification system of adenoid hypertrophy based on clinical experience on 7621 children.

Acta Otorhinolaryngol Ital 2022 Jun 8;42(3):257-264. Epub 2022 Apr 8.

Unit of Otolaryngology, University of Foggia, Foggia, Italy.

Introduction: Nasal endoscopy is likely to be the method of choice to evaluate nasal obstruction and adenoid hypertrophy (AH) in children given its excellent diagnostic accuracy and low risk for the patient. The aim of this study was to update the previous classification of AH to guide physicians in choosing the best therapeutic option.

Materials And Methods: This is a retrospective observational study including 7621 children (3565 females; mean age 5.92; range: 3-14 years) who were managed for adenoid hypertrophy at our institution between 2003 and 2018. All patients were initially treated with medical therapy and then with surgery if not adequately controlled. We performed a specific analysis based on the presence or absence of comorbidities.

Results: In 1845 (24.21%) patients, adenoid obstruction was classified as Grade I when the fiberoptic endoscopy showed adenoid tissue occupying < 25% of choanal space. In 2829 of 7621 (37.12%) patients, the adenoid tissue was scored as Grade II since it was confined to the upper half of nasopharynx, with sufficiently pervious choana and visualisation of tube ostium. In 1611 of 7621 (21.14%) cases, adenoid vegetation occupied about 75% of the nasopharynx with partial involvement of tube ostium and considerable obstruction of choanal openings, and was classified as Grade III. Finally, 1336 of 7621 (17.53%) patients were scored as Grade IV due to complete obstruction with adenoid tissue reaching the lower choanal border without allowing the visualisation of the tube ostium. Based on resolution of symptoms in Grade III obstruction after medical therapy (that was mostly seen in patients without comorbidities), we divided patients in two subclasses: Grade IIIA was not associated with comorbidities, while Grade IIIB was correlated with important comorbidities.

Conclusions: These results can be useful to guide medical or surgical therapeutic intervention. In patients with class IIIB AH, surgical treatment offered adequate control not only of nasal symptoms but also of associated comorbidities.
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http://dx.doi.org/10.14639/0392-100X-N1832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330757PMC
June 2022

Efficacy of Biologics on Refractory Eosinophilic Otitis Media Associated with Bronchial Asthma or Severe Uncontrolled CRSwNP.

J Clin Med 2022 Feb 10;11(4). Epub 2022 Feb 10.

Unit of Otorhinolaryngology-Head and Neck Surgery, "A. Gemelli" Hospital Foundation IRCCS, 00168 Rome, Italy.

Eosinophilic otitis media (EOM) is a difficult-to-treat otitis media characterized by eosinophilic accumulation in the middle ear mucosa and effusion. It is resistant to conventional treatments and strongly associated with asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). The aim of our study is to evaluate the effectiveness of biologics drugs in the control of EOM. This is a retrospective no-profit real-life observational study, involving patients affected by refractory EOM and in treatment with different biologics for concomitant severe eosinophilic asthma or severe uncontrolled CRSwNP (Dupilumab: = 5; Omalizumab: = 1; Mepolizumab: = 1; Benralizumab: = 1). We analyzed data at baseline and at the 6-month follow-up, including specific nasal and otological parameters. We observed an improvement of all nasal outcomes, including NPS, SNOT-22, VAS, and smell function. Regarding specific otological parameters, we observed a significant reduction in the mean value of COMOT-15 score and of Otitis Severity Score at 6-month follow-up compared to baseline ( < 0.05). Finally, we observed an improvement in terms of air conduction hearing levels during the treatment. Our results demonstrated that anti type-2 inflammatory pathway biologics can be effective in improving symptoms control and in reducing the severity of eosinophilic otitis media when treating coexisting type-2 diseases, such as asthma and or CRSwNP.
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http://dx.doi.org/10.3390/jcm11040926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8879230PMC
February 2022

Clinical Evidence of Type 2 Inflammation in Non-allergic Rhinitis with Eosinophilia Syndrome: a Systematic Review.

Curr Allergy Asthma Rep 2022 04 9;22(4):29-42. Epub 2022 Feb 9.

Department of Head and Neck Surgery - Otorhinolaryngology, Università Cattolica del Sacro Cuore, Rome, Italy.

Purpose Of Review: Non-allergic rhinitis (NAR) includes different subtypes, among which NAR with eosinophilia syndrome (NARES) is the most important because of severity of symptoms and the high risk of comorbidities. Its pathophysiology is still object of debate, but a crucial role of chronic eosinophilic inflammation has been recognized. The aim of this review is to critically analyze the current evidence regarding the hypothesis that NARES may be considered a type 2 inflammatory disorder.

Recent Findings: The definition and diagnostic criteria for NARES are not universally shared and adopted, thus generating difficulties in reproducing the results. At present, there is extreme heterogeneity in sampling methods and disagreement in the cut-off of local eosinophilic count to determine a diagnosis of NARES. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) standard was applied to identify English-language experimental and clinical articles regarding NARES. The search was performed in April 2021. Twenty-six articles were included. Our data suggest a particular heterogeneity regarding sampling and specific cut-offs adopted for diagnosis of NARES and consensus should be reached. We suggest that eosinophil count should be reported as an absolute value for at least 10 observed rich fields in order to increase the level of standardization. Consensus among authors on this topic should be reached with particular attention to the cut-off for diagnosis. In the future, this limitation may be overcome by the identification of repeatable biomarkers to refine diagnosis and prognosis of NARES. Furthermore, our data strongly suggest that NARES have numerous similarities with clinical features of the most common type 2 diseases such as eosinophilic asthma and chronic rhinosinusitis with nasal polyps (CRSwNP): late onset, association with type 2 comorbidities, selective eosinophilic tissue infiltration, remarkable response to oral and intranasal corticosteroids, and progression in a type 2 CRSwNP.
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http://dx.doi.org/10.1007/s11882-022-01027-0DOI Listing
April 2022

Long-term auditory follow-up in the management of pediatric platinum-induced ototoxicity.

Eur Arch Otorhinolaryngol 2022 Jan 13. Epub 2022 Jan 13.

Pediatric Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Sacro Cuore, 00168, Rome, Italy.

Purpose: Irreversible bilateral sensorineural hearing loss is a common side effect of platinum compounds. Because of the extended overall survival, a prolonged hearing surveillance and management of hearing impairments are emerging concerns for pediatric oncology.

Methods: In this retrospective observational study, we enrolled 38 children out of 116 treated at our institution by chemotherapy (cisplatin and/or carboplatin) with or without irradiation between 2007 and 2014, submitted to hearing monitoring before every cycle of chemotherapy, and who completed a 5-year long-term audiological follow-up. Chemotherapy regimens, demographic findings, cumulative doses, and cranial irradiation were compared.

Results: At the end of 5-year follow-up, ototoxicity was significantly increased compared to that observed at the end of chemotherapy (52.5% vs 39.5%, p < 0.001). A late onset of hearing loss was experienced in 13.1% of children, while in 26.3% progressive hearing loss was measured. Deafness at the end of chemotherapy and irradiation were significant prognostic factors for late ototoxicity outcomes (Odds Ratio 7.2-CI 1.67-31.1-p < 0.01 and 5.25-CI 1.26-21.86-p < 0.01 respectively). No significant differences were found between cisplatin and combined treatment (i.e., cisplatin shifted to carboplatin during monitoring for the onset of ototoxicity) and ototoxicity was not associated with platinum compounds cumulative dose (p > 0.05). 13.1% of children needed hearing aids at the end of follow-up.

Conclusion: Long-term monitoring of at least 5 years prevents the harmful effects of hearing deprivation identifying late onset/progressive hearing loss after platinum compound chemotherapy in children thanks to early hearing rehabilitation, especially in those who underwent multimodal therapy or subjected to irradiation.
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http://dx.doi.org/10.1007/s00405-021-07225-2DOI Listing
January 2022

Decision Making on Vestibular Schwannoma: Lessons from a Multidisciplinary Board.

World Neurosurg 2022 01 26;157:e506-e513. Epub 2021 Oct 26.

Department of Otolaryngology-Head and Neck Surgery, University Hospital of Modena, Modena, Italy.

Background: Management of vestibular schwannoma (VS) is a complex process aimed at identifying a clinical indication for fractionated stereotactic radiotherapy (sRT) or radiosurgery, microsurgical resection, or wait and scan (WS). We describe the experience of our VS multidisciplinary team (MDT) at a tertiary university referral center created for diagnosis, treatment, and follow-up of VS patients.

Methods: We conducted a retrospective study on 132 consecutive patients referred to the MDT and managed by observation (WS), microsurgery, or fractionated sRT. The analysis included patient age, tumor size, hearing level, facial nerve function, tumor control, complications, and quality of life questionnaires.

Results: Among the patients, 21% were subjected to microsurgery, 10% to sRT, and 69% to WS. The median follow-up time was 30 months. Outcomes based on different management modalities are described. Statistically significant differences among groups were detected in terms of quality of life (physical domain).

Conclusions: MDT may provide the best individualized therapy for VS patients compared with a single gold-standard strategy.
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http://dx.doi.org/10.1016/j.wneu.2021.10.140DOI Listing
January 2022

Nuclear HER3 expression improves the prognostic stratification of patients with HER1 positive advanced laryngeal squamous cell carcinoma.

J Transl Med 2021 09 27;19(1):408. Epub 2021 Sep 27.

Department of Histology, Università Cattolica del Sacro Cuore, Roma, Italy.

Background: Compared to the other members of human epidermal growth factor family receptors (HER), the role of HER3 has not been well defined in laryngeal cancer. The predictive and prognostic role of HER3 has been the focus of clinical attention but the research findings are contradictory, especially in laryngeal squamous cell carcinoma (LSCC). The variable localization of HER3 within cancer cells and the role of HER3 in primary and acquired resistance to HER1-targeted therapies remain unclear.

Methods: We performed a retrospective analysis of two cohorts of 66 homogeneous consecutive untreated primary advanced LSCC patients, in which co-expression of HER1, HER2 and HER3 receptors was investigated by semi-quantitative immunohistochemistry. The association of their pattern of expression with survival was evaluated by Kaplan-Meier and Cox's proportional hazard analyses. Multivariable Cox proportional hazards models were developed to predict median 2- and 3-year RFS and 2.5- and 5-year OS. The Akaike information criterion technique and backwards stepwise procedure were used for model selections. The performance of the final Cox models was assessed with respect to calibration and discrimination.

Results: Immunohistochemical labeling for HER1 and HER2 was localized both in the cell membrane and in the cytoplasm, while HER3 labeling was observed both in the cell cytoplasm and in the nucleus. HER3 expression was inversely correlated with HER1 positivity. The expression patterns of HERs were associated with tumor differentiation. In both cohorts of patients, HER1 expression was associated with reduced relapse-free (RFS) and overall survival (OS). In HER1 positive tumors, the co-expression with nuclear HER3 was associated with better RFS and OS, compared with HER3 negative tumors or tumors expressing HER3 at cytoplasmic level. HER3 expressing tumors had a higher Geminin/MCM7 ratio than HER3 negative ones, regardless of HER1 co-expression. Multivariable analyses identified age at diagnosis, tumor site, HER1, HER3 and age at diagnosis, tumor stage, HER1, HER3, as covariates significantly associated with RFS and OS, respectively. Bootstrapping verified the good fitness of these models for predicting survivals and the optimism-corrected C-indices were 0.76 and 0.77 for RFS and OS, respectively.

Conclusions: Nuclear HER3 expression was strongly associated with favourable prognosis and allows to improve the prognostic stratification of patients with HER1 positive advanced LSCC carcinoma.
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http://dx.doi.org/10.1186/s12967-021-03081-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8477517PMC
September 2021

Benign Paroxysmal Positional Vertigo (BPPV) in COVID-19.

Audiol Res 2021 Aug 13;11(3):418-422. Epub 2021 Aug 13.

Otolaryngology Institute-Department of Head and Neck, Fondazione Policlinico Universitario A Gemelli IRCCS, 00168 Rome, Italy.

Objective: The purpose of this article is to describe BPPV in COVID-19 patients by discussing the possible mechanisms underlying the onset of this vertigo.

Methods: We studied eight patients (4 F, 4 M, aged between 44 and 69 years) with COVID-19 infections complaining of vertigo. Patients were evaluated at the end of infection with an accurate clinical history, and the investigation of spontaneous, positional and positioning nystagmus.

Results: The vestibular findings showed benign paroxysmal positional vertigo (BPPV) in all the patients. Three patients had a mild phenotype of the COVID infection, whereas five subjects were hospitalized for the COVID infection and in three cases intensive care was required. Vestibular evaluation showed an involvement of posterior semicircular canals in five patients and horizontal in three. Three patients were treated with the Epley maneuver, two with Semont, one with Lempert and two with Gufoni maneuvers.

Conclusions: We hypothesize that BPPV in COVID-19 infections can be relate to drugs, prolonged bed rest and to direct damage by viral infection on the peripheral vestibular system and in particular on the otolitic membrane due to the cytopathic effect of the virus and to the inflammatory response. Studies on large series of patients are needed to confirm our preliminary observation and to better evaluate the pathophysiological mechanisms underlying BPPV in these patients.
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http://dx.doi.org/10.3390/audiolres11030039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395413PMC
August 2021

Sclerotherapy with polidocanol microfoam in head and neck venous and lymphatic malformations.

Acta Otorhinolaryngol Ital 2022 Apr 23;42(2):116-125. Epub 2021 Jul 23.

UOC Otorinolaringoiatria, Area Testa-Collo, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.

Objective: Polidocanol sclerotherapy of head and neck venous malformations (VMs) and lymphatic malformations (LMs) has been reported only in limited series. In this manuscript we evaluated the efficacy and safety of polidocanol sclerotherapy in a series of head and neck venous and lymphatic malformations.

Methods: This retrospective observational study analysed data on 20 head and neck VMs and LMs that underwent to percutaneous or endoscopic intra-lesional 3% polidocanol microfoam sclerotherapy at our institution. Clinical response was ranked as excellent, moderate and poor based on volume reduction by MRI and resolution of symptoms.

Results: The median volume decreased from 19.3 mL to 5.8 mL after sclerotherapy (mean volume reduction: 72.98 ± 16.1%). An excellent-moderate response was observed in 94.4% of cases. We observed a mean volume reduction of 79.5 ± 16.1 in macrocystic LMs, of 76.1 ± 13.0% in VMs, of 60.5 ± 10.9% in mixed lymphatic ones and 42.5% in microcystic lymphatic ones.

Conclusions: Polidocanol sclerotherapy appears to be an effective and safe treatment for venous and lymphatic head and neck malformations. We observed the best responses in macrocystic LMs and VMs, whereas mixed lymphatic ones showed a moderate response and microcystic lymphatic ones a poor response.
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http://dx.doi.org/10.14639/0392-100X-N1310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9131995PMC
April 2022

The evaluation of global cognitive and emotional status of older patients with chronic tinnitus.

Brain Behav 2021 08 21;11(8):e02074. Epub 2021 Jul 21.

Institute of Otolaryngology, Fondazione Policlinico Agostino Gemelli, IRCCS, Rome, Italy.

Objectives: Tinnitus is a common symptom largely impactful on quality of life, especially in the elderly. Our aim was to evaluate the efficacy of self-administered screening tests to correlate the severity of subjective perception of tinnitus with emotional disorders and the overall cognitive status.

Methods: Patients aged ≥ 55 years with chronic tinnitus were recruited and submitted to a complete audiological evaluation; Tinnitus Handicap inventory (THI); Hospital Anxiety and Depression Scale (HADS-A and HADS-D) and Mini-Mental State Examination (MMSE). Demographic and audiological features of patients with and without cognitive impairment (MMSE score cut-off of 24/30) were analyzed in order to reveal the relationship among tinnitus, emotional disorders, and cognitive dysfunction.

Results: 102 patients were recruited (mean age: 70.4 ± 9.6). THI score was directly related to HADS-A score (r = .63) HADS-D score (r = .66), whereas there was no relationship between tinnitus severity and MMSE (r = .13). CI and n-CI groups did not differ in the characteristics of tinnitus (p > .05), however, hearing threshold (p = .049) and anxious depressive traits measured with HADS-A (p = .044) and HADS-D (p = .016) were significantly higher in the group with cognitive impairment. Furthermore, age ≥ 75 years (p = .002, OR = 13.8), female sex (p = .032; OR = 6.5), severe hearing loss (p = .036; OR = 2.3), and anxiety (p = .029; OR = 9.2) resulted risk factors for CI. Therefore, in CI group MMSE score was inversely related to age (r = -.84).

Conclusions: Cognitive impairment and psychiatric discomfort should be considered in tinnitus patients, related to increasing age, female sex, and severe hearing loss. Thus, self-administered questionnaires can be useful in addressing clinical approach.
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http://dx.doi.org/10.1002/brb3.2074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413806PMC
August 2021

Cross-cultural adaptation and Italian validation of chronic otitis media outcome test 15 (COMOT-15).

Acta Otorhinolaryngol Ital 2021 Jun;41(3):277-281

Department of Neuroscience, Reproductive and Odontostomatological Sciences - ENT section, University "Federico II", Naples, Italy.

Objective: Chronic suppurative otitis media (CSOM) may result in a serious impairment of the quality of life (QoL). The most relevant characteristics of CSOM are well represented in the "Chronic Otitis Media Outcome Test 15" questionnaire (COMOT-15). The aim of the study was to translate and adapt the COMOT-15 questionnaire into Italian.

Methods: This is a prospective study conducted on 52 Caucasian Italian-speaking patients with CSOM and 52 controls. The linguistic adaptation of the COMOT-15 consisted of the translation of the English version into Italian and reliability assessment of the translation. Psychometric measurements included internal consistency and test-retest reliability.

Results: Cronbach's α was 0.95. The test-retest reliability showed a strong positive correlation for total score and all subscales. Age and gender had no influence on the scores. The correlation between the COMOT-15 and the pure tone average showed a significant association for the scale "Hearing Function".

Conclusions: The Italian COMOT-15 questionnaire provides good internal consistency and is suitable for QoL evaluation in Italian-speaking patients suffering from CSOM. In addition, it is able to evaluate the subjective symptoms perceived by patients.
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http://dx.doi.org/10.14639/0392-100X-N1184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283399PMC
June 2021

A systematic review of the clinical evidence and biomarkers linking allergy to adeno-tonsillar disease.

Int J Pediatr Otorhinolaryngol 2021 Aug 12;147:110799. Epub 2021 Jun 12.

Department of Neuroscience, Reproductive and Odontostomatological Sciences - ENT Section, University "Federico II", Naples, Italy.

Introduction: allergy may be an important risk factor for adenotonsillar disease in children, although conflicting results have been reported in the literature. In previous articles, authors often failed in distinguishing between adeno-tonsillar hypertrophy and recurrent tonsillitis and in not discriminating between isolated or combined adenoid and tonsillar hypertrophy.

Aim: to evaluate clinical evidence and biomarkers linking allergy to different phenotypes of adeno-tonsillar disease. Furthermore, we questioned whether anti-allergy treatment might prevent occurrence of adeno-tonsillar disease or improve its specific management.

Methods: our systematic review, in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) process, yielded 1010 articles finally screened. This resulted in 21 full texts that were included in a qualitative analysis.

Results: literature data support the association between allergy and combined adeno-tonsillar hypertrophy and isolated adenoid hypertrophy, whereas describe a mainly negative correlation between allergy and isolated tonsillar hypertrophy. The results of this review suggest that local allergic inflammation may play a role in adeno-tonsillar hypertrophy. Data correlating bacterial recurrent tonsillitis and allergy are few, although evidence from the lab revealed that allergy might suppress innate immunity in tonsillar tissue by reducing levels of anti-microbial proteins.

Conclusion: basing on our qualitative analyses allergy should not be misdiagnosed in children with combined adenotonsillar hypertrophy or isolated adenoid hypertrophy, whereas evidence do not support a link between allergy and isolated tonsil hypertrophy. Finally, some data support a link between allergy and recurrent adeno-tonsillar infection although future studies are required to confirm this data. We summarized our conclusions in a practical algorithm.
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http://dx.doi.org/10.1016/j.ijporl.2021.110799DOI Listing
August 2021

Multidisciplinary approach to nose vestibule malignancies: setting new standards.

Acta Otorhinolaryngol Ital 2021 Apr;41(Suppl. 1):S158-S165

UOC di Otorinolaringoiatria, Dipartimento Scienze dell'Invecchiamento, Neurologiche, Ortopediche e della Testa Collo, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy.

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http://dx.doi.org/10.14639/0392-100X-suppl.1-41-2021-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172111PMC
April 2021

Cooperation between ENT surgeon and dentist in head and neck oncology.

Acta Otorhinolaryngol Ital 2021 Apr;41(Suppl. 1):S124-S137

Head and Neck Oncology Service, Candiolo Cancer Institute - FPO, IRCCS, Candiolo, Italy.

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http://dx.doi.org/10.14639/0392-100X-suppl.1-41-2021-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172104PMC
April 2021

Tinnitus and Neuropsychological Dysfunction in the Elderly: A Systematic Review on Possible Links.

J Clin Med 2021 Apr 27;10(9). Epub 2021 Apr 27.

Department of Otolaryngology Head & Neck Surgery, School of Medicine, Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy.

Introduction: Tinnitus is a common and disabling symptom often associated with hearing loss. While clinical practice frequently shows that a certain degree of psychological discomfort often characterizes tinnitus suffers, it has been recently suggested in adults as a determining factor for cognitive decline affecting attention and memory domains. The aim of our systematic review was to provide evidence for a link between tinnitus, psychological distress, and cognitive dysfunction in older patients and to focus on putative mechanisms of this relationship.

Methods: We performed a systematic review, finally including 192 articles that were screened. This resulted in 12 manuscripts of which the full texts were included in a qualitative analysis.

Results: The association between tinnitus and psychological distress, mainly depression, has been demonstrated in older patients, although only few studies addressed the aged population. Limited studies on cognitive dysfunction in aged patients affected by chronic tinnitus are hardly comparable, as they use different methods to validate cognitive impairment. Actual evidence does not allow us with certainty to establish if tinnitus matters as an independent risk factor for cognitive impairment or evolution to dementia.

Conclusion: Tinnitus, which is usually associated with age-related hearing loss, might negatively affect emotional wellbeing and cognitive capacities in older people, but further studies are required to improve the evidence.
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http://dx.doi.org/10.3390/jcm10091881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123622PMC
April 2021

Patient-reported olfactory recovery after SARS-CoV-2 infection: A 6-month follow-up study.

Int Forum Allergy Rhinol 2021 08 4;11(8):1249-1252. Epub 2021 Feb 4.

Department of Otolaryngology-Head and Neck Surgery, AOU Policlinico and University of Modena and Reggio Emilia, Modena, Italy.

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http://dx.doi.org/10.1002/alr.22775DOI Listing
August 2021

Otitis media in children: Which phenotypes are most linked to allergy? A systematic review.

Pediatr Allergy Immunol 2021 04 11;32(3):524-534. Epub 2021 Jan 11.

Department of Head and Neck Surgery - Otorhinolaryngology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.

Background: Allergic rhinitis is a common childhood disease responsible for a major impact on quality of life and healthcare resources. Many hypotheses have been proposed to explain the link between allergy and otitis media, although a definitive mechanism has not been identified yet. One of the major critical points is that authors failed in distinguishing among different phenotypes of middle ear inflammation. This review pointed out literature evidence from the laboratory and clinical experience linking allergy to different phenotypes of otitis media in children.

Methods: We performed a systematic review in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) process. Our search yielded 3010 articles that were finally screened. This resulted in 20 manuscripts of which the full texts were included in a qualitative analysis. We paid particular attention in distinguishing among phenotypes of otitis media.

Results: Clinical evidence and analyses of biomarkers suggested that allergy may be linked to some phenotypes of otitis media and, in particular, to otitis media with effusion (OME) and acute re-exacerbations in children with middle ear effusion. It was not possible to perform the analysis for allergy and acute and chronic otitis media because of paucity and heterogeneity of data.

Conclusion: Allergy should be considered in the diagnostic workup of children with OME as well as OME should be excluded in children with persistent moderate to severe AR. In these cases, clinicians should evaluate prompt and accurate treatment of allergy in improving outcomes, although futures studies are required to increase evidence supporting that anti-allergy treatment may be effective in the recovery and outcome of otitis media with effusion.
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http://dx.doi.org/10.1111/pai.13431DOI Listing
April 2021

Functional results of exclusive interventional radiotherapy (brachytherapy) in the treatment of nasal vestibule carcinomas.

Brachytherapy 2021 Jan-Feb;20(1):178-184. Epub 2020 Oct 9.

UOC di Otorinolaringoiatria, Dipartimento Scienze dell'Invecchiamento, Neurologiche, Ortopediche e della testa collo. Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy; Institute of Otolaryngology, Università Cattolica del Sacro Cuore, Policlinico Agostino Gemelli, Rome, Italy.

Purpose: Surgery, external beam radiotherapy (EBRT), and interventional radiotherapy (IRT, BrachyTherapy BT) are the current therapeutic options for nose vestibule (NV) squamous cell carcinoma (SCC). In this article, we evaluate the nose functional parameters of patients affected by SCCs of the NV, primarily treated by interstitial IRT comparing them with healthy controls and with patients treated with intensity-modulated EBRT.

Methods: Ten patients treated by using IRT (group 1), 10 healthy controls and eight patients treated by EBRT (group 2) on the region of the nose were submitted to clinical evaluation (with the NOSE scale score), rhinomanometry, olfactory testing, nasal citology, and evaluation of mucociliary clearance through saccharine test.

Results: No long-term skin or cartilaginous toxicity are recorded. The olfactometry threshold discrimination identification TDI is lower in EB group. The mean NOSE scale score was significantly higher in group 2 than in group 1 and healthy controls (p < 0.05). The distribution of cytologic patterns resulted significantly different as well. Patients treated by EB have a significantly impaired mucociliary clearance, with a mean time for the transport of the stained marker, which is more than double in the patients treated by EB than in those treated with IRT (p < 0.001).

Conclusions: Nasal function and cytological findings are significantly better, substantially preserved, in patients treated by IRT than in those treated by EBRT, bringing new relevant evidence for the establishment of interstitial IRT as the new standard for the treatment of the primary lesion in cT1 and cT2 -Wang staging NV SCCs.
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http://dx.doi.org/10.1016/j.brachy.2020.08.008DOI Listing
August 2021
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