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Introduction: Primary hyperparathyroidism (PHPT) is a common endocrine disorder in which surgery is the only curative therapy. Ectopic parathyroid adenoma in the pyriform sinus resulting from a pathological migration of parathyroid glands along the embryological development is a rare cause of PHPT. We describe a case of a persistent primary hyperparathyroidism after previous unsuccessful surgery due to an ectopic parathyroid adenoma within the pyriform sinus and we review the previous reports on this issue., Case Presentation: A 62-year-old woman was referred for persistent hypercalcemia following unsuccessful cervical exploratory surgery. Cervical ultrasound did not detect any parathyroid abnormalities. At variance, 99m Tc-sestamibi SPECT/CT and CT scan of the neck identified a parathyroid adenoma in the left pyriform sinus, which was confirmed by endoscopy. The patient was successfully treated by transoral robotic resection and the pathology confirmed a parathyroid adenoma., Conclusions: The ectopic parathyroid adenoma in the pyriform sinus is so uncommon that only fourteen cases have been reported. However, the pyriform sinus should be considered a possible location of ectopic parathyroid glands, especially in the setting of persistent or recurrent PHPT after parathyroid surgery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Sardella, Seccia, Giambalvo, Pierotti, Dinoi, Della Valentina, Pardi, Materazzi, Dallan, Berrettini and Cetani.)

Background: Severe Eosinophilic Asthma (SEA) may be the prodromal phase of Eosinophilic Granulomatosis with Polyangiitis (EGPA). Nevertheless, few studies have tried to recognize EGPA in the early stages of the disease., Objectives: To identify a panel of clinical and biological markers to detect which severe asthmatic patient might be considered in a prodromal phase of EGPA and crafting a strategy for diagnostic decision-making., Methods: 30 patients with EGPA and 49 with SEA were enrolled. A complete pulmonary, ear, nose and Throat (ENT) and rheumatologic assessment were made. Blood (eosinophil count, eosinophilic cationic protein-ECP, IL5, IL4, total-IgE, IgG4, anti-neutrophil cytoplasmic antibody (ANCA), sputum (eosinophils count, periostin, IL8 and GMCSF) and nasal smear (eosinophilia) biomarkers were assessed. Asthma Control Test, Short Form-36, SinoNasalOutcome Test-22, and Asthma Quality of Life Questionnaire were also used., Results: SEA patients had poorer asthma control (p<0.001) and higher level of sputum eosinophils (p<0.002) while EGPA patients reported higher levels of blood eosinophils in the past. Sputum GMCSF was the only biomarker significantly increased in EGPA patients compared with SEA (p<0.0001). Among SEA patients, those with some suggestive but not diagnostic criteria of EGPA, particularly tissue eosinophilic infiltrates, presented higher levels of sputum GMCSF (p<0.0005), blood and sputum eosinophils (p<0.0006, p<0.011) in comparison with the other patients., Conclusion: Sputum GMCSF and eosinophils might be useful biomarkers to support early diagnosis and treatment choices in SEA patients, suspected of having EGPA., (Copyright © 2024. Published by Elsevier Inc.)

Competing Interests: BD received grants for speeches and advisory boards from Angelini, Astrazeneca, GSK, Novartis, Sanofi and Zambon. BL received fees from Astrazeneca, GSK, Novartis and Sanofi. BC received fees from GSK, Novartis and Sanofi. CL received fees for lectures from Alk Abellò, Astrazeneca, GSK, Novartis and Sanofi. DCE received fees for consultation, lectures and advisory board from Astrazeneca, GSK, Novartis, Regeneron and Sanofi. LMI reveived fees from Chiesi, DMG Firma, GSK, Novartis and Sanofi. MG has received fees from GSK, Novartis and Sanofi. MA received fee for advisory board and speaker for Astra Zeneca, Chiesi, CSL Boerhing, GSK, Novartis, Sanofi, and Takeda. SV partecipated in advisory boards and scientific meetings on behalf of Astrazeneca, Firma, GSK, Novartis and Sanofi. VA received fees for lectures and advisory boards from Astrazeneca, GSK, Novartis, and Sanofi. PP received grants for speeches and expert opinion from GSK, LeoPharma, and Novartis. CFRM received fees from GSK, Novartis and Sanofi. RM and SC are GSK full time employes. Macchi A, ML, NS, PG and PL declare to have no conflicts of interest.

Purpose of Review: We aimed to reach an Italian multidisciplinary consensus on some crucial aspects of treatment decision making in CRSwNP, following 2 years of clinical experience in order to support specialists in the management of CRSwNP in clinical practice. We addressed issues relating to therapeutic decision-making and shared criteria for the treatment choice, as well as appropriate timing and criteria for evaluating treatment response, and highlighted the need for repeated multidisciplinary assessments., Recent Findings: A national survey has been conducted recently to understand how rhinology practice has changed in Italy with the advent of biologics and how this affects patients with uncontrolled, severe CRSwNP. Despite the many published consensus documents, practical recommendations, and protocols on the use of biologics in CRSwNP, heterogenous behaviors in practice are still observed mainly conditioned by the novelty of the topic. The consensus procedure followed a modified Delphi approach. The scientific board included 18 otorhinolaryngologists and 8 allergists, who selected the 4 main topics to be addressed and developed overall 20 statements. Consensus on these statements was sought by a larger group of 48 additional experts, through two rounds of voting, the first web-based, the second in presence with discussion and possible refinement of the statements. The statements reaching an average score ≥ 7 at the second voting round were approved. Five statements were proposed for each of the following topics: baseline evaluation of patients eligible for biologic therapy; choice between different therapeutic options; assessment of the response to biologic treatment; multidisciplinary management. At the first voting round, 19 out of the 20 statements reached a mean score ≥ 7. Following the discussion and a few consequent amendments, at the second round of voting all the 20 statements were approved., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose of Review: The development of biological therapies for type 2 inflammatory diseases raises the possibility of addressing remission in those dis-immune conditions. No consensus exists for a definition of remission in chronic rhinosinusitis with nasal polyps (CRSwNP). This review aims to critically evaluate the published data to provide the basis for defining remission in CRSwNP., Recent Findings: The published evidence has yet to provide an unequivocal definition on remission in type 2 inflammatory diseases, in part reflecting differences in approaches to diagnosis and follow-up. A multidimensional evaluation is necessary when considering complete remission, including clinical, inflammatory, and histologic criteria, but how to combine or tailor the three perspectives according to disease severity at baseline or timing of assessment of treatment category is yet to reach consensus. We suggest defining remission starting from the approach taken in asthma and eosinophilic esophagitis, that is, including the resolution of symptoms and improvements in objective parameters of disease severity and/or inflammatory activity. Future studies and consensuses should provide validated criteria with cutoffs for the day-to-day definition of remission. The definition of remission in CRSwNP should include the following criteria, to be verified and maintained for a period of ≥ 12 months: absence of symptoms (nasal obstruction, loss of smell, rhinorrhea as the main ones); no impact of symptoms on quality of life; no need of surgery; no chronic or rescue medications (systemic corticosteroids or antibiotics); and recovery of smell function, possibly evaluated by objective test. Assessment of underlying inflammation should also be considered once accurate and feasible biomarkers are available in clinical practice., (© 2023. The Author(s).)

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a disease with a significant impact on quality of life. The overall goal of CRSwNP management, as with other chronic conditions, is to achieve "disease control", and for that reason, a definition of control of disease is pivotal in deciding the best treatment strategy. Although many staging systems have already been developed to evaluate the disease, disease control is not yet to be standardized, and a specific tool that is consistently applied and accepted by all practitioners is still missing in daily clinical practice. To gain an overview of the implementation and limitations of existing guidelines and to shed light on real-life definitions of control and disease severity, we conducted a nationwide survey of otorhinolaryngologists routinely treating CRSwNP to identify unmet clinical needs in Italy. The results showed homogeneous responses regarding the knowledge contained in international guidelines while highlighting the difficulty of their implementation in day-to-day practice. Respondents called attention to the importance of clinical symptoms, giving more weight to the patient's perspective. Among the symptoms to be considered, respondents emphasized nasal obstruction, followed by loss of sense of smell and rhinorrhea. Others also believe that the physician's perspective should be considered, and the inclusion of endoscopy as a measure of control was warranted by many. The need for a specific tool that is able to unequivocally ascertain disease control is increasingly pivotal in this new era of biologics for treating CRSwNP.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with significant morbidity and reduced health-related quality of life. Findings from clinical trials have demonstrated the effectiveness of dupilumab in CRSwNP, although real-world evidence is still limited., Methods: This Phase IV real-life, observational, multicenter study assessed the effectiveness and safety of dupilumab in patients with severe uncontrolled CRSwNP (n = 648) over the first year of treatment. We collected data at baseline and after 1, 3, 6, 9, and 12 months of follow-up. We focused on nasal polyps score (NPS), symptoms, and olfactory function. We stratified outcomes by comorbidities, previous surgery, and adherence to intranasal corticosteroids, and examined the success rates based on current guidelines, as well as potential predictors of response at each timepoint., Results: We observed a significant decrease in NPS from a median value of 6 (IQR 5-6) at baseline to 1.0 (IQR 0.0-2.0) at 12 months (p < .001), and a significant decrease in Sino-Nasal Outcomes Test-22 (SNOT-22) from a median score of 58 (IQR 49-70) at baseline to 11 (IQR 6-21; p < .001) at 12 months. Sniffin' Sticks scores showed a significant increase over 12 months (p < .001) compared to baseline. The results were unaffected by concomitant diseases, number of previous surgeries, and adherence to topical steroids, except for minor differences in rapidity of action. An excellent-moderate response was observed in 96.9% of patients at 12 months based on EPOS 2020 criteria., Conclusions: Our findings from this large-scale real-life study support the effectiveness of dupilumab as an add-on therapy in patients with severe uncontrolled CRSwNP in reducing polyp size and improving the quality of life, severity of symptoms, nasal congestion, and smell., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Objective: We conducted a national survey to understand how rhinology practice has changed with the advent of biologics and how this affected patients with uncontrolled, severe chronic rhinosinusitis with nasal polyps (CRSwNP). We aimed to analyse the results of the survey and infer practical recommendations for clinical practice., Methods: A group of ear, nose, and throat specialists (ENTs) experienced in the management of CRSwNP developed a 74-question survey. ENTs from rhinology centres authorised to prescribe biologics in the context of the national health system were invited to answer it between 01/05/2022 and 31/07/2022. The responses underwent descriptive analyses, and the authors discussed the results and derived practical recommendations for clinical practice., Results: ENTs working in rhinology centres changed their practices coinciding with the advent of biologics. CRSwNP evaluations have become more complex because they involve diagnostic confirmation, determining the patients' immunologic profile, and other factors. We observed heterogenous behaviours in practice that may be conditioned by the novelty of the topic. The results of the survey were used to develop practical recommendations for ENTs and are summarised herein., Conclusions: Clinical practice in rhinology outpatient clinics has changed profoundly in the era of biologics. Our practical recommendations for clinicians working in rhinology centres are expected to help standardise practice and improve care., (Copyright © 2023 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

Chronic rhinosinusitis (CRS) is a complex and heterogeneous disorder whose etiopathogenetic picture is not yet completely known and is classically divided into CRS with (CRSwNP) and without nasal polyps (CRSsNP). But today the distinction is made with type 2 and nontype 2 variants. A rational and defined pathway for the diagnosis of chronic rhinosinusitis is an indispensable means to be able to arrive at a correct identification of the patient. This typing is essential to be able to arrive at the correct course of treatment, which turns out to be different for different types of patients. For this reason, the realization of a diagnostic therapeutic pathway represents a fundamental way for the otolaryngologist specialist but not only, since today diagnostics has a multidisciplinary framework. In the present work, precise indications have been developed to arrive at a correct diagnosis. The various diagnostic pathways and processes to arrive at a correct therapeutic framing have been highlighted. Therapy ranging from medical therapy to surgical therapy without neglecting the new biological therapies. It does not represent a guideline but a diagnostic method that can be adapted to all the various territorial realities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Canevari, Giorli, Monti, Biagini, Bagnasco, Cavaliere, Pipolo, De Corso, Gelardi, Gramellini, loppi, La Mantia, Malvezzi, Bignami, Dehgani-Mobaraki, Seccia, Maggiore, Macchi.)

Introduction: The impairment of the sense of smell is often related to chronic rhinosinusitis (CRS) with or without nasal polyps (CRSwNP, CRSsNP). CRSwNP is a frequent condition that drastically worsens the quality of life of those affected; it has a higher prevalence than CRSsNP. CRSwNP patients experience severe loss of smell with earlier presentation and are more likely to experience recurrence of their symptoms, often requiring revision surgery., Methods: The present study performed a multicentric data collection, enrolling 811 patients with CRS divided according to the inflammatory endotype (Type 2 and non-Type 2). All patients were referred for nasal endoscopy for the assessment of nasal polyposis using nasal polyp score (NPS); Sniffin' Sticks olfactory test were performed to measure olfactory function, and SNOT-22 (22-item sinonasal outcome test) questionnaire was used to assess patients' quality of life; allergic status was evaluated with skin prick test and nasal cytology completed the evaluation when available., Results: Data showed that Type 2 inflammation is more common than non-type 2 (656 patients versus 155) and patients suffer from worse quality of life and nasal polyp score. Moreover, 86.1% of patients with Type 2 CRSwNP were affected by a dysfunction of the sense of smell while it involved a lesser percentage of non-Type 2 patients. Indeed, these data give us new information about type-2 inflammation patients' characteristics., Discussion: The present study confirms that olfactory function weights on patients' QoL and it represents an important therapeutic goal that can also improve patients' compliance when achieved. In a future - and present - perspective of rhinological precision medicine, an impairment of the sense of smell could help the clinician to characterize patients better and to choose the best treatment available., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Macchi, Giorli, Cantone, Carlotta Pipolo, Arnone, Barbone, Bertazzoni, Bianchini, Ciofalo, Cipolla, De Massimi, De Vita, Di Lieto, Ghidini, Govoni, Gramellini, Maselli Del Giudice, Ottaviano, Seccia, Sireci, Sollini, Staffieri, Gallo, Heffler, Mantia, De Corso, Canevari, Lombardo, Malvezzi, Orietti, Pasquini, Presutti and Monti.)

Background: Patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) often require repeat sinus surgery. Mepolizumab reduced the need for sinus surgery in the SYNAPSE trial; this analysis sought to provide a more in-depth assessment of surgery endpoints in SYNAPSE., Methods: SYNAPSE was a double-blind Phase III trial (NCT03085797) in adults with recurrent, refractory, severe, CRSwNP eligible for repeat sinus surgery despite standard of care treatments and previous surgery. Patients were randomized (1:1) to mepolizumab 100 mg subcutaneously or placebo, plus standard of care, every 4 weeks for 52 weeks. Time to first inclusion on a waiting list for sinus surgery and time to first actual sinus surgery (both up to week 52) were assessed; the latter endpoint was also analyzed post hoc according to time since last sinus surgery before study screening and baseline blood eosinophil count., Results: Among 407 patients (mepolizumab: 206; placebo: 201), mepolizumab versus placebo reduced the risk of being included on a waiting list for sinus surgery (week 52 Kaplan-Meier probability estimate [95% confidence interval]: 13.9% [9.8%, 19.5%] vs. 28.5% [22.7%, 35.4%]). Mepolizumab versus placebo reduced the risk of sinus surgery irrespective of time (<3 vs ≥3 years) since patients' last sinus surgery prior to study screening (hazard ratios [95% confidence intervals] 0.28 [0.09, 0.84] and 0.50 [0.26, 0.98], respectively) and baseline blood eosinophil count., Conclusions: Mepolizumab reduced the risk of further sinus surgery in patients with recurrent, refractory, severe CRSwNP, irrespective of the patient baseline characteristics assessed., (© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Introduction: Cutaneous squamous cell carcinoma (cSCC) is a frequent skin cancer with a high risk of recurrence characterized by tumor infiltration and, in advanced cases, a poor prognosis. ECT (electrochemotherapy) is an alternative treatment option for locally advanced or recurrent cSCC that is unsuitable for surgical resection. In this study, we aimed to evaluate the data in the InspECT (International Network for Sharing Practice on ECT) registry of the referral centers and to clarify the indications for the use of ECT as a treatment modality for cSCC., Materials and Methods: Patients with primary, recurrent or locally advanced cSCC from 18 European centers were included. They underwent at least one ECT session with bleomycin between February 2008 and November 2020, which was performed following the European Standard Operating Procedures., Results: The analysis included 162 patients (mean age of 80 years; median, 1 lesion/patient). Side effects were mainly local and mild (hyperpigmentation, 11%; ulceration, 11%; suppuration, 4%). The response to treatment per patient was 62% complete and 21% partial. In the multivariate model, intravenous drug administration and small tumor size showed a significant association with a positive outcome (objective response). One-year local progression-free survival was significantly better (p<0.001) in patients with primary tumors (80% (95% C.I. 70%-90%) than in patients with locally advanced disease (49% (95% C.I. 30%-68%)., Conclusion: In the present study, ECT showed antitumor activity and a favorable safety profile in patients with complex cSCC for whom there was no widely accepted standard of care. Better results were obtained in primary and small tumors (<3 cm) using intravenous bleomycin administration., Competing Interests: FT is an IGEA employer. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bertino, Groselj, Campana, Kunte, Schepler, Gehl, Muir, Clover, Quaglino, Kis, Mascherini, Bisase, Pecorari, Bechara, Matteucci, Odili, Russano, Orlando, Pritchard-Jones, Moir, Mowatt, Silvestri, Seccia, Saxinger, de Terlizzi and Sersa.)

Objective: The upcoming introduction of mepolizumab represents a promising treatment for chronic rhinosinusitis with nasal polyps (CRSwNP). The present study aimed to evaluate the effectiveness of mepolizumab on sinonasal outcomes of comorbid CRSwNP and severe asthma in a real-life setting. The primary endpoint was to evaluate changes in the SinoNasal Outcome Test (SNOT)-22 score, Nasal Polyp (NP) score, and blood eosinophil count during a 12-month treatment with mepolizumab. Secondary endpoints were to quantify mepolizumab’s effects on the mentioned parameters, identify clinical variables influencing the degree of response to treatment, and portray responder and nonresponder patients. Methods: A multicentric retrospective no-profit observational study on severe asthmatic patients, treated with mepolizumab, and comorbid CRSwNP was conducted. All patients were followed for at least 12 months. SNOT-22 score, NP score, and blood eosinophil count (and other CRS-specific variables) were collected at baseline and after 12 months. Results: Forty-three patients were included. A statistically significant reduction was observed for SNOT-22 score (mean t0 SNOT-22 54.8 ± 25.9; mean t12 SNOT-22 31.5 ± 21.3, p < 0.0001), NP score (median t0 NPS 3 (IQR 3); median t12 NPS 2 (IQR 4), p < 0.0001), and blood eosinophil count (mean t0 blood eosinophils 804.7 ± 461.5 cell/µL; mean t12 blood eosinophils 107.5 ± 104.6 cell/µL, p < 0.0001) after 12 months of treatment. Twenty patients (47%) gained improvement both in clinical and endoscopic outcome. Mepolizumab responder patients presented a t0 SNOT-22 significantly higher than nonresponders (p = 0.0011). Conclusions: Mepolizumab improved CRSwNP outcomes in a population of severe asthmatic patients. No clinical feature emerged to outline the profile of a “typical” responder patient, except for baseline SNOT-22 score, which seemed to affect the response to treatment. Further studies would be necessary to supplement these preliminary evaluations.

This prospective registry-based study aims to describe electrochemotherapy (ECT) modalities in basal cell carcinoma (BCC) patients and evaluate its efficacy, safety, and predictive factors. The International Network for Sharing Practices of Electrochemotherapy (InspECT) multicentre database was queried for BCC cases treated with bleomycin-ECT between 2008 and 2019 (n = 330 patients from seven countries, with 623 BCCs [median number: 1/patient; range: 1-7; size: 13 mm, range: 5-350; 85% were primary, and 80% located in the head and neck]). The procedure was carried out under local anaesthesia in 68% of cases, with the adjunct of mild sedation in the remaining 32%. Of 300 evaluable patients, 242 (81%) achieved a complete response (CR) after a single ECT course. Treatment naïvety (odds ratio [OR] 0.35, 95% confidence interval [C.I.] 0.19-0.67, p = 0.001) and coverage of deep tumour margin with electric pulses (O.R. 5.55, 95% C.I. 1.37-21.69, p = 0.016) predicted CR, whereas previous radiation was inversely correlated (O.R. 0.25, p = 0.0051). Toxicity included skin ulceration (overall, 16%; G3, 1%) and hyperpigmentation (overall, 8.1%; G3, 2.5%). At a 17-month follow-up, 28 (9.3%) patients experienced local recurrence/progression. Despite no convincing evidence that ECT confers improved outcomes compared with standard surgical excision, it can still be considered an opportunity to avoid major resection in patients unsuitable for more demanding treatment. Treatment naïvety and coverage of the deep margin predict tumour clearance and may inform current patient selection and management.

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.

Purpose: Differentiating Warthin tumor (WT) from pleomorphic adenoma (PA) is of primary importance due to differences in patient management, treatment and outcome. We sought to evaluate the performance of MRI-based radiomic features in discriminating PA from WT in the preoperative setting., Methods: We retrospectively evaluated 81 parotid gland lesions (48 PA and 33 WT) on T2-weighted (T2w) images and 52 of them on post-contrast fat-suppressed T1-weighted (pcfsT1w) images. All MRI examinations were carried out on a 1.5-Tesla MRI scanner, and images were segmented manually using the software ITK-SNAP (www.itk-snap.org)., Results: The most discriminative feature on pcfsT1w images was GLCM&#95;InverseVariance, yielding area under the curve (AUC), sensitivity and specificity of 0.9, 86 % and 87 %, respectively. Skewness was the feature extracted from T2w images with the highest specificity (88 %) in discriminating WT from PA., Conclusion: Radiomic analysis could be an important tool to improve diagnostic accuracy in differentiating PA from WT., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors.)

Introduction: S. aureus is a major opportunistic pathogen that has been implicated in the pathogenesis of several chronic inflammatory diseases including bronchial asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), chronic spontaneous urticaria (CSU), and atopic dermatitis. S. aureus can induce the production of both polyclonal and specific IgE that can elicit an inflammatory cascade., Areas Covered: The link between the sensitization to S. aureus enterotoxins and the severity of several chronic inflammatory diseases is reviewed in detail, as well as its therapeutic implications., Expert Opinion: An anti-IgE strategy to inhibit S. aureus enterotoxins would be a valid approach to treat several endotypes of severe asthma, CRSwNP and CSU in which IgE against S. aureus enterotoxins should represent, not only a marker of severity of the diseases but also a target of a treatment.

Background : 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. Methods : 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. Results : 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. Conclusions : 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.

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.

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., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a predominantly type 2 inflammation-mediated disease of the nasal mucosa and paranasal sinuses that often coexists with asthma. The role of atopy in the development and severity of CRSwNP is still a controversial issue., Objective: The aim of our study was to propose a systematic allergy workup to identify atopic patients in the context of CRSwNP and to characterize their allergen sensitization profile (sources/molecules)., Methods: Patients with a diagnosis of CRSwNP (n = 97) were studied in the otorhinolaryngologist and allergy settings. Demographic and clinical data were collected for each patient. Different allergen sensitization profiles (sources/molecules) were evaluated in atopic CRSwNP patients by using component-resolved diagnosis (CRD)., Results: In our cohort of patients, the CRSwNP was frequently diagnosed during adulthood with significant impact on health-related quality of life. Asthma and atopy were the most common comorbidities with a prevalence of asthma in the atopic group. In CRSwNP patients sensitized to grass pollens and/or to house dust mites, the CRD analysis revealed a prevalence of sensitization to species-specific allergens of Phleum pratense (Phl p1, Phl p2, and Phl p5) or Dermatophagoides pteronyssinus (Der p1 and Der p2) rather than to cross-reactive ones., Conclusion: To define the allergen sensitization profile in atopic CRSwNP patients by CRD, it may be useful to better characterize type 2 inflammation, thus providing a personalized endotype-driven treatment., (© 2022 S. Karger AG, Basel.)

Nasal polyps (NPs) are benign inflammatory masses causing chronic nasal obstruction, usually associated with underlying chronic rhinosinusitis (CRS), which are rarely reported in childhood. The interest in NPs has recently increased due to new therapeutic options, namely biological agents, such as dupilumab, and an update of the European position paper on this topic was released in 2020, providing a detailed classification for these lesions and also discussing diagnostic and therapeutic approaches also in children. In childhood, NPs usually represent red flags for systemic diseases, such as cystic fibrosis and immunodeficiencies. This review outlines the recent data on NPs in childhood, focusing on predisposing factors for CRS as well as on the potential endotypes in this particular age group, for which further studies are required in order to better clarify their pathogenesis and to identify molecular biomarkers that could help achieve more personalized treatments.

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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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., (© 2021 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Purpose: Spontaneous skull base cerebrospinal fluid leaks occurring without any apparent cause are rare. But those patients that present such leaks simultaneously, or successively, in multiple locations are even rarer. Given the rarity of this condition, we collected data from other groups in a multicentre study to reach an adequate number of patients and draw some preliminary considerations., Methods: We carried out a multicentre retrospective study on a cohort of patients treated at third level hospitals in Italy, Spain, United Kingdom and Greece for multiple spontaneous-CSF leaks and we compared them with a control group of patients treated for recurrent spontaneous-CSF leaks. Data regarding clinical aspects, radiological findings, surgical techniques and outcome were collected and preliminary considerations on the results were discussed., Results: A total of 25 patients presented multiple simultaneous spontaneous CSF leaks while 18 patients fit with the criteria of recurrent spontaneous CSF leaks. Data analysis was conducted separately., Conclusions: Our understanding of the pathogenesis of this condition is currently very limited. A causative role of IIH may be present but the differences that emerged from the comparison with patients with recurrent fistulas seem to promote the possible role of other cofactors. A longer follow-up period is needed, and, in our opinion, prospective and multicentre studies are the only solution to seriously deal with such a complex topic.

Our purpose is to evaluate the performance of magnetic resonance (MR) radiomics analysis for differentiating between malignant and benign parotid neoplasms and, among the latter, between pleomorphic adenomas and Warthin tumors. We retrospectively evaluated 75 T2-weighted images of parotid gland lesions, of which 61 were benign tumors (32 pleomorphic adenomas, 23 Warthin tumors and 6 oncocytomas) and 14 were malignant tumors. A receiver operating characteristics (ROC) curve analysis was performed to find the threshold values for the most discriminative features and determine their sensitivity, specificity and area under the ROC curve (AUROC). The most discriminative features were used to train a support vector machine classifier. The best classification performance was obtained by comparing a pleomorphic adenoma with a Warthin tumor (yielding sensitivity, specificity and a diagnostic accuracy as high as 0.8695, 0.9062 and 0.8909, respectively) and a pleomorphic adenoma with malignant tumors (sensitivity, specificity and a diagnostic accuracy of 0.6666, 0.8709 and 0.8043, respectively). Radiomics analysis of parotid tumors on conventional T2-weighted MR images allows the discrimination of pleomorphic adenomas from Warthin tumors and malignant tumors with a high sensitivity, specificity and diagnostic accuracy.

Background: Electrochemotherapy (ECT) is a treatment for both primary and secondary cutaneous tumours. The international Network for sharing practices on ECT group investigates treatment outcomes after ECT using a common database with defined parameters., Methods: Twenty-eight centres across Europe prospectively uploaded data over an 11-year period. Response rates were investigated in relation to primary diagnosis, tumour size, choice of electrode type, route of bleomycin administration, electrical parameters recorded and previous irradiation in the treated field., Results: Nine hundred eighty-seven patients, with 2482 tumour lesions were included in analysis. The overall response (OR) rate was 85% (complete response [CR]: 70%, partial response rate: 15%, stable disease: 11%, and progressive disease: 2%). For different histologies, OR and CR rates for metastases of malignant melanoma were 82% and 64%, basal cell carcinoma were 96% and 85%, breast cancer metastases were 77% and 62%, squamous cell carcinoma were 80% and 63% as well as Kaposi's sarcoma were 98% and 91%, respectively. Variance was demonstrated across histotypes (p < 0.0001) and in accordance with size of lesion treated (dichotomised at diameter of 3 cm (p < 0.0001). Hexagonal electrodes were generally used for larger tumours, but for tumours up to 3 cm, linear array electrodes provided better tumour control than hexagonal electrodes (80%:74%, p < 0.003). For tumours more than 2 cm, intravenous administration was superior to intratumoural (IT) administration (p < 0.05). Current recorded varied across tumour histologies and size but did not influence response rate. In previously irradiated areas, responses were selectively lower for IT administration., Conclusions: These cumulative data endorse efficiency of ECT across a broad range of histotypes. Analysis of 2482 lesions details subgroup analysis on treatment response informing future treatment choices., Competing Interests: Conflict of interest statement The following authors have conflict of interest: A.J.P.C. reports receiving travel fees for a meeting related to manuscript preparation by IGEA. F.d.T. is an employee of IGEA. J.O. reports receiving travel fees and accommodation fees from IGEA. L.G.C. reports receiving travel support for the International Network for Sharing Practice in Electrochemotherapy (InspECT) meeting from IGEA. D.M. reports receiving travel fees and accommodation fees for InspECT meeting from IGEA. A.D.M.R. reports receiving flight and accommodation fees for electrochemotherapy meeting and has aso received an honorarium. J.G. reports receiving travel fees and accommodation for a meeting related to manuscript preparation from IGEA. The other authors report no conflict of interest., (Copyright © 2020. Published by Elsevier Ltd.)

Background: The evolution of endoscopic skull base approaches has enabled surgeons to manage selected skull base tumors through a transnasal endoscope-assisted approach. On the other side, more extensive lesions may require a combined cranioendoscopic approach. In this paper, we analysed and compared the incidence of frontal lobe sagging after endoscopic multilayer (EM) reconstruction versus pericranial flap (PF) reconstruction., Methodology: Subjects were selected retrospectively according to specific inclusion and exclusion criteria. The degree of frontal lobe sagging after surgery was calculated based on the most inferior position of the frontal lobe relative to the nasion-sellar line defined on preoperative and postoperative imaging. A positive value signified upward displacement, and a negative value represented frontal lobe sagging., Results: Twenty subjects were enrolled in our study. In the EM technique group the average frontal lobe displacement was -2,34 ± 1,55 mm. The average postoperative frontal lobe sagging was -0,45 ± 8,92 mm in subjects reconstructed with the PF. The skull base defect size correlated with the degree of frontal lobe sagging in subjects reconstructed with the PF, but not in the other group and when merging the two groups., Conclusions: In conclusion, the EM technique and the PF reconstruction showed a good reliability for the closure of anterior skull base defects. Moreover the PF seemed to prevent frontal lobe sagging but, for larger skull base defects, it could be useful to be combined with other autologous or heterologous materials to avoid the frontal lobe falling.

Purpose of the Review: We provide a systematic review of experimental and clinical evidences linking allergy to acute, including common cold, and chronic rhinosinusitis in children. Furthermore, we questioned if anti-allergy treatment may prevent the occurrence of rhinosinusitis or improve outcomes of its specific management., Recent Findings: Allergic rhinitis is a common childhood disease in industrialized countries that is responsible for a major impact on quality of life and healthcare resources. Over the years many authors tried to correlate allergy with comorbidities and in particular to the onset of rhinosinusitis including common cold, even though conflicting results are frequently reached. We performed a systematic review in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) process. Our search yielded 7103 that were finally screened. This resulted in 25 publications of which the full texts were assessed and included in a qualitative analysis per different phenotypes of rhinosinusitis. The evidence suggests that allergy may lead to overall impairment of mechanical and immunological defense function of the nasal mucosa against viruses and that anti-allergy treatment may significantly decrease the number and severity of upper respiratory tract infections including common colds in children. It was not possible to perform the analysis for allergy and post-viral acute rhinosinusitis, bacterial acute rhinosinusitis, and recurrent acute rhinosinusitis because of paucity and heterogeneity of data. Although there is no definitive proof of causation linking allergy to chronic rhinosinusitis, studies lead to suppose that anti-allergy treatment may improve outcomes of specific CRS treatments.

Background: Among chordoma patients, recurrent cases are by far more complex to be managed, and cranio-cervical junction (CCJ) localizations represent a particular challenge due to the complexity of the anatomical region which makes it difficult to obtain a radical resection., Methodology: We report our personal experience in treating four patients with recurrent CCJ chordoma with "personalized" multiportal and eventually multistage approaches., Conclusions: Endoscopic endonasal approaches have gained widespread acceptance and are considered the workhorse in most cases of craniocervical junction chordomas. Nonetheless, in some cases of recurrence, or in presence of very lateralized lesions/ anatomical variations midline approaches are either contraindicated or very difficult to perform. In all these cases it seems reasonable to consider a versatile strategy including different approaches, modulating the surgical needs with different answers and solutions offered by the different routes. In other words to personalize as much as possible the approach, being creative and not dogmatic.

The purpose of this study was to define the proteome profile of fine needle aspiration (FNA) samples of malignant major salivary gland tumors (MSGT) compared to benign counterparts, and to evaluate potential clinical correlations and future applications. Patients affected by MSGT (n = 20), pleomorphic adenoma (PA) (n = 37) and Warthin's tumor (WT) (n = 14) were enrolled. Demographic, clinical and histopathological data were registered for all patients. FNA samples were processed to obtain the protein extracts. Protein separation was obtained by two-dimensional electrophoresis (2-DE) and proteins were identified by mass spectrometry. Western blot analysis was performed to validate the 2-DE results. Statistical differences between groups were calculated by the Mann-Whitney U test for non-normal data. Spearman's rank correlation coefficient was calculated to evaluate correlations among suggested protein biomarkers and clinical parameters. Twelve and 27 differentially expressed spots were found for MSGT versus PA and MSGT versus WT, respectively. Among these, annexin-5, cofilin-1, peptidyl-prolyl-cis-trans-isomerase-A and F-actin-capping-alpha-1 were able to differentiate MSGT from PA, WT, and healthy samples. Moreover, STRING analysis suggested cofilin-1 as a key node of protein interactions. Some of the overexpressed proteins are related to some clinical factors of our cohort, such as survival and outcome. Our results suggest potential protein biomarkers of MSGT, which could allow for more appropriate treatment plans, as well as shedding light on the molecular pathways involved.

Background: Ecchordosis physaliphora is a congenital, benign lesion originating from notochordal remnants along the craniospinal axis, most frequently located at the level of the clivus and sacrum. Sometimes ecchordosis physaliphora is difficult to recognise and treat, with a total of twenty-six cases described in the literature., Methods: This study reports on three cases of previously undiagnosed ecchordosis physaliphora presenting with cerebrospinal fluid rhinorrhoea and meningitis., Conclusion: Endoscopic transclival or transsphenoid surgery including three-layer (fat, fascia and nasoseptal flap) reconstruction was used in all cases with complete resolution of the symptoms.

Background and Aims: Severe asthma may require the prescription of one of the biologic drugs currently available, using surrogate markers of airway inflammation (serum IgE levels and allergic sensitization for anti-IgE, or blood eosinophils for anti-IL5/IL5R). Our objective: to assess upper and lower airway inflammation in severe asthmatics divided according to the eligibility criteria for one of the target biologic treatments., Methods: We selected 91 severe asthmatics, uncontrolled despite high-dose ICS-LABA, and followed for >6 months with optimization of asthma treatment. Patients underwent clinical, functional and biological assessment, including induced sputum and nasal cytology. They were then clustered according to the eligibility criteria for omalizumab or mepolizumab/benralizumab., Results: Four clusters were selected: A (eligible for omalizumab, n  = 23), AB (both omalizumab and mepolizumab, n  = 26), B (mepolizumab, n  = 22) and C (non-eligible for both omalizumab and mepolizumab, n  = 20). There was no difference among clusters for asthma control (Asthma Control Test and Asthma Control Questionnaire 7), pre-bronchodilator forced expiratory volume in 1 s, serum IgE and fractional exhaled nitric oxide levels. Sputum eosinophils were numerically higher in clusters AB and B, in agreement with the higher levels of blood eosinophils. Allergic rhinitis was more frequent in clusters A and AB, while chronic rhinosinusitis with nasal polyps prevalence increased progressively from A to C. Eosinophils in nasal cytology were higher in clusters AB, B and C., Conclusion: Eosinophilic upper and lower airway inflammation is present in the large majority of severe asthmatics, independently from the prescription criteria for the currently available biologics, and might suggest the use of anti-IL5/IL5R or anti IL4/13 also in patients without blood eosinophilia. The reviews of this paper are available via the supplemental material section .

Purpose: Transoral robotic surgery (TORS) and maxillo-mandibular advancement (MMA) are effective options for obstructive sleep apnea patients. Identification of the correct candidate is by far the most important item in achieving a succesful outcome. As a consequence, not all patients can be managed successfully via one or the other procedure. To overcome the limits of any single procedure we have combined, in a very selected population of patients, TORS tongue base reduction and MMA. Preliminary data are encouraging, in terms of both AHI and ESS., Methods: A retrospective cohort study was conducted on five patients treated with combined TORS-MMA surgery. Demographic and clinical data, pre-operative and post-operative PSG and ESS were collected., Results: Three of five patients were recruited. All patients presented severe OSAHS. Mean AHI and ESS went respectively from 48 and 12 pre-operatively to 19 and 4 post-operatively. Minor bleeding occurred in two patients. No significant sequelae have been reported., Conclusions: Combined TORS and MMA is feasible and safe. Our very preliminary data are encouraging, in terms of both AHI and ESS. Long-term follow-up and a larger amount of subjects are needed to confirm this surgical approach as a valuable option for selected OSAHS patient.

Salivary gland tumors (SGTs) are rare tumors of the head and neck with different clinical behavior. Preoperative diagnosis, based on instrumental and cytologic examinations, is crucial for their correct management. The identification of molecular markers might improve the accuracy of pre-surgical diagnosis helping to plan the proper treatment especially when a definitive diagnosis based only on cytomorphology cannot be achieved. miRNAs appear to be new promising biomarkers in the diagnosis and prognosis of cancer. Studies concerning the useful of miRNA expression in clinical decision-making regarding SGTs remain limited and controversial.The expression of a panel of 798 miRNAs was investigated using Nanostring technology in 14 patients with malignant SGTs (6 mucoepidermoid carcinomas, 4 adenoid cystic carcinomas, 1 acinic cell carcinoma, 1 ductal carcinoma, 1 cystadenocarcinoma and 1 adenocarcinoma) and in 10 patients with benign SGTs (pleomorphic adenomas). The DNA Intelligent Analysis (DIANA)-miRPath v3.0 software was used to determinate the miRNA regulatory roles and to identify the controlled significant Kyoto Encyclopedia of Genes and Genomes (KEGG) molecular pathways. Forty six miRNAs were differentially expressed (False Discovery Rate-FDR<0.05) between malignant and benign SGTs. DIANA miRPath software revealed enriched pathways involved in cancer processes as well as tumorigenesis, cell proliferation, cell growth and survival, tumor suppressor expression, angiogenesis and tumor progression. Interestingly, clustering analysis showed that this signature of 46 miRNAs is able to differentiate the two analyzed groups. We found a correlation between histological diagnosis (benign or malignant) and miRNA expression profile.The molecular signature identified in this study might become an important preoperative diagnostic tool., Competing Interests: The authors have declared that no competing interests exist.

Background: According to ATS/ERS document on severe asthma (SA), the management of these patients requires the identification and proper treatment of comorbidities, which can influence the control of asthma., Methods: The aim of this study was to assess the independent effect of different comorbidities on clinical, functional and biologic features of SA. Seventy-two patients with SA according to GINA guidelines were examined. We collected demographic data, smoking habit, asthma history, and assessment of comorbidities. Pulmonary function, inflammatory biomarkers, upper airway disease evaluation, asthma control and quality of life were carefully assessed., Results: The mean age of patients was 59.1 years (65.3% female, 5.6% current smokers). Comorbidities with higher prevalence were: chronic rhinosinusitis with or without nasal polyps (CRSwNP or CRSsNP), obesity and gastro-esophageal reflux (GERD), with some overlapping among them. In an univariate analysis comparing patients with single comorbidities with the other ones, asthmatics with CRSwNP had lower lung function and higher sputum eosinophilia; obese asthmatics had worse asthma control and quality of life, and tended to have lower sputum eosinophils; asthmatics with GERD showed worse quality of life. In multivariate analysis, obesity was the only independent factor associated with poor asthma control (OR 4.9), while CRSwNP was the only independent factor associated with airway eosinophilia (OR 16.2). Lower lung function was associated with the male gender and longer duration of asthma (OR 3.9 and 5.1, respectively) and showed a trend for the association with nasal polyps (OR 2.9, p = 0.06)., Conclusion: Our study suggests that coexisting comorbidities are associated with different features of SA.

Background and Purpose: A prospective instrumental assessment of late dysphagia using swallowing organs at risk (SWOARs)-sparing IMRT for nasopharyngeal and oropharyngeal cancers., Materials and Methods: Objective instrumental assessment included fiberoptic endoscopic evaluation of swallowing (FEES) and videofluoroscopy (VFS) at baseline, and at 6 and 12 months after treatment. FEES assessed the pharyngeal residue according to the Farneti pooling score (P-score) as follows: 4-5 no dysphagia; 6-7 mild dysphagia; 8-9 moderate dysphagia; 10-11 severe dysphagia. Three different consistencies were tested for the P‑score: liquid (L), semisolid (SS), and solid (S). VFS assessed penetration-aspiration according to the Penetration-Aspiration Scale (PAS) and two different consistencies of the bolus were tested: thin liquid barium (L) and paste barium (S)., Results: 38 patients were evaluable. There was a significant worsening of the P‑score at 6 months both for SS (p = 0.015) and S (p < 0.001), which persisted only for S at 12 months (p < 0.0001). Similarly, there was a significant worsening of the PAS score at 6 and 12 months (p = 0.065 and 0.039, respectively) for the S bolus. Overall, 3-7 and 10-14% aspiration after L and S was observed, respectively., Conclusions: Promising results using a SWOARs-sparing IMRT technique are reported. Therefore, treatment plans should be optimized for reducing doses to these structures.

Nasal cytology is a precious tool to study nasal disorders, but in current literature, there is no consensus on the standardization of the processing procedure of the obtained samples. Therefore, we decided to test on specimens obtained by nasal scraping, a common way of nasal specimen sampling, two different processing techniques, smear and cytocentrifugation, and compare them in terms of inflammatory cell content, quality of slides, and validity on clinical assessment. We analyzed 105 patients with suspected sinonasal diseases, and in each patient, we performed nasal cytology with both techniques. Our analysis showed a good correlation between the two techniques for neutrophil and eosinophil percentages, both returned well-preserved cells, and showed higher neutrophil percentage in males and in smokers and higher eosinophil percentage in patients with polyposis, with a good concordance with clinical symptoms, as measured by a specific disease-related questionnaire (Sino-Nasal Outcome Test-22). Technically speaking, smeared slides were easier to prepare, with no need of dedicated equipment, but cell distribution was better in cytocentrifuged slides allowing shorter reading time. In conclusion, both techniques can be considered superimposable and worthy to be used.

Nasal cytology is an easy, cheap, non-invasive and point-of-care method to assess nasal inflammation and disease-specific cellular features. By means of nasal cytology, it is possible to distinguish between different inflammatory patterns that are typically associated with specific diseases (ie, allergic and non-allergic rhinitis). Its use is particularly relevant when other clinical information, such as signs, symptoms, time-course and allergic sensitizations, is not enough to recognize which of the different rhinitis phenotypes is involved; for example, it is only by means of nasal cytology that it is possible to distinguish, among the non-allergic rhinitis, those characterized by eosinophilic (NARES), mast cellular (NARMA), mixed eosinophilic-mast cellular (NARESMA) or neutrophilic (NARNE) inflammation. Despite its clinical usefulness, cheapness, non-invasiveness and easiness, nasal cytology is still underused and this is at least partially due to the fact that, as far as now, there is not a consensus or an official recommendation on its methodological issues. We here review the scientific literature about nasal cytology, giving recommendations on how to perform and interpret nasal cytology., (© 2018 John Wiley & Sons Ltd.)

Purpose: Parotidectomy may be burdened by numerous complications that may worsen subjects' quality of life (QoL). These include paresis or paralysis of the facial nerve, face profile asymmetry, keloids, salivary fistula, Frey Syndrome (FS), First Bite Syndrome (FBS), and hypo-anaesthesia of the skin. This study is an effort to assess the incidence of complications following parotidectomy and their impact on subjects' QoL., Methods: Subjects undergoing parotidectomy for benign neoplasms from 2012 to 2015 were selected and invited to attend our outpatient clinic. After a brief anamnesis, the medical examiners tested their tactile perception and performed the Minor test for FS. Depending on the complications showed, subjects were asked to complete from 1 to 4 questionnaires about their QoL., Results: 76 subjects completed the medical examination. The most frequent complication was the hypo-anaesthesia of the skin (71%). 21 subjects (28%) were positive to the Minor test, while 8 subjects (11%) reported FBS-compatible symptoms. Two subjects (3%) showed a facial nerve paralysis. Free abdominal fat graft was used in 16 subjects (21%) and it was associated with a lower incidence of FS. Surgery of the deep lobe of the parotid was associated with FBS., Conclusions: FBS appears to have a greater influence on subjects' QoL than FS and hypo-anaesthesia of the skin. Moreover, this work confirms that surgery of the deep lobe of the parotid is a risk factor for developing FBS and the free abdominal fat graft is a reliable technique to prevent FS.

Background: Eosinophilic granulomatosis with polyangiitis and granulomatosis with polyangiitis show variable otorhinolaryngological involvement. Up to 14 per cent of granulomatosis with polyangiitis patients have subglottis involvement; little is known about the laryngeal involvement in eosinophilic granulomatosis with polyangiitis., Method: A literature review was conducted, together with a prospective cross-sectional analysis of 43 eosinophilic granulomatosis with polyangiitis patients. All patients underwent fibre-optic laryngoscopy with narrow-band imaging, and completed health-related questionnaires., Results: The literature review showed only two cases of laryngeal involvement in eosinophilic granulomatosis with polyangiitis; in our cohort, no cases of subglottis stenosis were found, but local signs of laryngeal inflammation were present in 72 per cent of cases. Of the patients, 16.2 per cent had a pathological Reflux Finding Score (of 7 or higher)., Conclusion: Laryngeal inflammation in eosinophilic granulomatosis with polyangiitis is frequent. It is possibly due more to local factors than to eosinophilic granulomatosis with polyangiitis itself. However, ENT evaluation is needed to rule out possible subglottis inflammation. These findings are in line with current literature and worthy of confirmation in larger cohorts.

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a necrotizing vasculitis that predominantly affects small- to medium-sized vessels. It is characterized by a wide spectrum of extrapulmonary symptoms, including sinonasal and paranasal sinus abnormalities. These are the most common features of this disease, constituting diagnostic criteria for EGPA. However, the actual clinical features, cellular mechanisms and impact on patients' quality of life (QoL) are still a matter of study., Methods: Thirty-nine EGPA patients underwent multidimensional rhinological evaluations, including rhinofibroscopy, nasal cytology, and QoL questionnaires. This was coupled with respiratory and rheumatological assessments., Results: Twenty-eight patients were diagnosed with chronic rhinosinusitis (CRS). Of these, 18 had nasal polyposis (NP). Chronic rhinitis was diagnosed in 10 patients. Of these, 3 had allergic rhinitis (AR) and seven had non-AR (NAR). Overall, only 1 patient (2.6%) was normal. Nasal cytology showed that hypereosinophilia was present in 17/28 patients with CRS, 4/7 patients with NAR and all patients with AR. SNOT-22 and SF-36 showed a severe impact of nasal symptoms on QoL. No differences in asthma control or rheumatological patterns for EGPA were observed among patients with or without NP., Conclusions: Even when the rheumatological assessment scored EGPA "under control" according to the Birmingham Vasculitis Activity Score and Vasculitis Damage Index, sinonasal diseases and related nasal inflammatory processes were not controlled. Therefore, there is a need for clinical monitoring and targeted treatment to control the inflammatory processes and improve the QoL of EGPA patients., (© 2018 S. Karger AG, Basel.)

Objective: To assess changes of CT perfusion parameters (ΔPCTp) of cervical lymph node metastases from head and neck cancer (HNC) before and after radiochemotherapy (RT-CT) and their association with nodal tumor persistence., Patients and Methods: Eligibility criteria included HNC (Stage III-IV) candidates for RT-CT. Patients underwent perfusion CT (PCT) at baseline 3 weeks and 3 months after RT-CT. Blood volume (BV), blood flow (BF), mean transit time (MTT) and permeability surface (PS) were calculated. PET/CT examination was also performed at baseline and 3 months after treatment for metabolic assessment., Results: Between July 2012 and May 2016, 27 patients were evaluated. Overall, only 3 patients (11%) experienced tumor persistence in the largest metastatic lymph node. A significant reduction of all PCTp values (p<0.0001), except MTT (from 6.3 to 5.7 s; p=0.089), was observed at 3 weeks post-RT-CT compared to baseline. All PCTp values including MTT were significantly lower at 3-month follow-up compared to baseline (p<0.05). Moreover, a statistically significant association was observed between nodal tumor persistence and high BF values (p=0.045) at 3 months after treatment that did not occur for the other parameters., Conclusions: Our preliminary findings show that all PCTp except MTT are significantly reduced after RT-CT. High BF values at 3 months post-RT-CT are predictive of nodal tumor persistence.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common inflammatory disorder that strongly impacts patients' quality of life. CRSwNP is still a challenge for ENT specialists due to its unknown pathogenesis, difficult control and frequent relapse. We tested the hypothesis that a new standardised therapeutic approach based on individual clinical-cytological grading (CCG), may improve control of the disease and prevent the needing for surgery. We analysed 204 patients suffering from bilateral CRSwNP, 145 patients of whom regularly assumed therapy, respecting the planned check-up, and were considered cases; 59 patients were not assuming therapy as indicated and were considered as controls. After five years of standardised treatment, 15 of 145 (10.5%) improved endoscopic staging, 61 of 145 (42%) did not change their endoscopic staging, and 69 of 145 (47.5%) were worse. In the control group, 49 of 59 (83%) were worse by at least two stages (p < 0.05). Patients and controls were stratified basing on clinical and cytological grading as mild, moderate and severe. After patient stratification, in the mild group (n = 27) 92% patients had a constant trend, with no worsening and no need for surgery over a 5-year period, whereas in the mild CCG control group 1 of 59 (1.6%) required surgery (p < 0.05). In moderate GCC (n = 83), 44% of patients did not modify or improve endoscopic staging and 3.6% needed surgery, compared to 13.6% of controls with moderate GCC (p < 0.05). In severe CCG (n = 35), even though no patients achieved significant amelioration of endoscopic grading, 40% of patients were considered as "clinically controlled" and 5.7% of patients underwent surgery, but the percentage was significantly higher (49%) in the control group significant (p = 0.0000). Finally, statistical analyses revealed a clear trend that polyp size increased at a faster rate in the control group than in the treatment group and for each subgroup (low, moderate and severe). The present study suggests a new approach in the management of CRS according to clinical cytological grading that allows defining the grade of CRSwNP severity and to adapt the intensity of treatment. This approach limited the use of systemic corticosteroids to only moderate-severe CRSwNP with a low corticosteroid dosage in comparison with those previously suggested. Our protocol seems to improve the adherence by patients, control of disease and the need for surgery in the long-term., (© Copyright by Società Italiana di Otorinolaringologia e Chirurgia Cervico-Facciale, Rome, Italy.)

Inflammatory non-allergic rhinitis (INAR) is characterized by the presence of an inflammatory infiltrate and a non-IgE-mediated pathogenesis. This retrospective, controlled, multicentre study investigated whether a symbiotic, containing Lactobacillus acidophilus NCFM, Bifidobacterium lactis, and fructo-oligosaccharides (Pollagen®, Allergy Therapeutics, Italy), prescribed as adjunctive therapy to a standard pharmacological treatment, was able to reduce symptom severity, endoscopic features, and nasal cytology in 93 patients (49 males and 44 females, mean age 36.3±7.1 years) with INAR. The patients were treated with nasal corticosteroid, oral antihistamine, and isotonic saline. At randomization, 52 patients were treated also with symbiotic as adjunctive therapy, whereas the remaining 41 patients served as controls. Treatment lasted for 4 weeks. Patients were visited at baseline, after treatment, and after 4-week follow-up. Adjunctive symbiotic treatment significantly reduced the percentages of patients with symptoms and endoscopic signs, and diminished inflammatory cells. In conclusion, the present study demonstrates that a symbiotic was able, as adjuvant treatment, to significantly improve symptoms, endoscopic feature, and cytology in patients with INAR, and its effect may be long lasting.

Objectives/hypothesis: To evaluate the clinical features of audiologic impairment and its relationship with the nasal, vestibular, and rheumatologic profile in a cohort of patients with eosinophilic granulomatosis with polyangiitis (EGPA), formerly named Churg-Strauss syndrome., Study Design: Prospective cross-sectional study., Methods: Thirty-nine patients with EGPA, considered controlled according to the Birmingham Vasculitis Activity Score and the Vasculitis Damage Index, underwent a complete audiologic evalutaion with otomicroscopy, impedance audiometry, speech audiometry, and auditory brainstem responses; rhinologic evaluation was made by means of fiberoptic endoscopy and nasal cytology; the clinical evaluation was completed with analysis of the facial function and, in patients with referred vertigo, with videonystagmography (VNG). Data were compared to the rheumatologic profile (eosinophil count, antineutrophil cytoplasmic antibodies status)., Results: Thirty-four of 39 patients fulfilled the inclusion criteria. Of those, 18 (52, 8%) were affected by variable degrees of hearing loss (sensorineural hearing loss [SNHL]) in four cases (11, 8%), mixed sensorineural and conductive hearing loss in two (5, 9%), presbycusis in six (17, 6%), and otitis media with effusion (OME) in six (17, 6%). Vestibular impairment was represented by benign paroxysmal positional vertigo and unspecific dizziness in three (8, 8%) and four cases (11, 8%), respectively, all with normal VNG. Ear involvement was statistically related to the EGPA vasculitic pattern and independent from the nasal impairment, cytology, and duration of nasal symptoms. No facial palsy was registered., Conclusion: In our experience, the largest in the existing literature, the otological involvement in EGPA is common and may occur variably as SNHL or OME. Otological involvement occurs early in the course of the disease process, but is nonspecific in making the diagnosis of EGPA. Its recognition is therefore fundamental., Level of Evidence: 4. Laryngoscope, 126:2792-2797, 2016., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

The parapharyngeal space (PPS) is a challenging anatomical region, rich in vascular and nervous vital structures. Surgery is considered the treatment of choice for the majority of PPS lesions. Herein, we present a retrospective evaluation on ten patients with various types of lesions of the parapharyngeal and infratemporal fossa (ITF) regions operated on via an endoscopic-assisted transoral-transpharyngeal approach (EATTA), focusing on feasibility and safety. A retrospective evaluation of patients treated by means of EATTA to PPS and/or ITF lesions was carried out. The clinical records of patients who were operated on with EATTA for PPS and/or ITF lesions between March 2009 and October 2015 at two referral centres were reviewed and the intra-operative and post-operative complications were analysed. Ten patients who underwent EATTA on the PPS and ITF were included in this series. The procedure was performed in six patients for tumour removal, in three patients for diagnostic purposes and in one patient for pain control. No major complications occurred. No conversion to external approach was required. We observed only two minor complications which were promptly solved. No dysphagia or other problems during the food intake were observed in our series. One day after surgery all patients, except one, referred a value of VAS minor than 4. To date, no evidence of disease recurrence has been assessed in all six oncological cases. Although preliminary, our experience seems to demonstrate the feasibility and safety of EATTA when properly planned and performed.

In recent decades, the management of sinonasal tumors abutting the orbit has been widely discussed. A real guideline has yet to be proposed, as prospective randomized studies on this topic are very difficult to organize, given the relative rarity of this pathology, the wide spectrum of histologic patterns, and the different clinical behavior of tumors. Nevertheless, in recent years, a better assessment of tumor extension has been obtained thanks to the refinement of preoperative imaging tools and, therefore, more conservative approaches could be adopted, with no worsening of the oncological outcomes and, at the same time, with more attention given to the post-surgical quality of life. Currently, tumors that extend to the bony orbital walls with or without focal infiltration of the periorbit are amenable to orbital preservation. On the other hand, infiltration of extraocular muscles and neurovascular structures are an indication to orbital exenteration. The ideal surgical treatment in cases of limited involvement of orbital fat still remains a matter of debate. We report and discuss the recent English literature on this interesting topic.