Effectiveness of dupilumab versus endoscopic sinus surgery for the treatment of type-2 chronic rhinosinusitis with nasal polyps: a preliminary report.

PURPOSE: Historically managed with intranasal corticosteroids (INCS) and endoscopic sinus surgery (ESS), type-2 Chronic RhinoSinusitis with Nasal Polyps (CRSwNP) treatment was revolutionized by the introduction of dupilumab but universally accepted guidelines are still lacking. METHODS: Patients treated at our University Hospital for type-2 CRSwNP were enrolled. Demographic data were collected, as well as laboratory (eosinophils, total IgE), endoscopic [nasal polyps score (NPS), modified Lund-Kennedy score (mLKS)], radiological [Lund-Mackay score (LMS) at CT scan], SNOT-22, and olfactory [Sniffin' Sticks identification test (SSIT)] features. Patients were treated with dupilumab or ESS and re-evaluated after 3 and 12 months. RESULTS: At 3 and 12 months, patients undergoing ESS achieved a higher reduction of NPS and mLKS, while patients receiving dupilumab experienced a higher improvement at SNOT-22 and SSIT with a greater positive variation in the prevalence of anosmia (- 57.7% vs - 42.9%) and normosmia (+ 37.8 vs + 28.5%). Mean mLKS and LMS were quite similar. Results were independent of clinical features known to contribute to CRSwNP severity, except for patients with ≥ 2 prior ESS who had a significantly lower smell improvement. CONCLUSION: ESS and dupilumab were effective at reducing CRSwNP inflammatory burning. CRSwNP smell impairment cannot be attributed only to olfactory cleft obstruction and other mechanisms may be involved. Dupilumab acts systemically with poor correlation with NPS. As of today, dupilumab appears to be more suitable for elderly patients with anesthesiological contraindications and/or several previous surgeries, while ESS may represent the first-line choice in surgery-naive patients.

Efficacy and safety of dupilumab in the treatment of CRSwNP in the real-life setting: a review of the literature.

INTRODUCTION: The recent approval of Dupilumab has profoundly revolutionized the management of patients affected by severe and recalcitrant Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). However, a review that summarizes the results of real-life studies and compares them to phase 3 studies SINUS-24 and 52 is still lacking. MATERIALS AND METHODS: A search of all real-life studies published from 2019 to 2023 was performed. Patients characteristics at baseline and 6 and 12 months after starting Dupilumab were extracted and compared to those from phase 3 trials: age, sex, smoking habits, comorbid asthma and aspirin-exacerbated respiratory disease (AERD), previous endoscopic sinus surgery (ESS), hematic eosinophils and total IgE, NasalAQ2 Polyps Score (NPS), smell, SNOT-22, adverse events (AEs), and response to treatment. RESULTS: 15 papers were included with an overall number of 1658 patients. A higher rate of comorbidities and previous ESS was found in patients from real-life studies. In addition, they had worse smell and SNOT-22 at baseline compared to patients from SINUS-24 and 52. Comorbid and post-ESS patients tended to have a faster NPS and SNOT-22 improvement, although the absolute values were not clinically relevant. A more extensive surgery and a number of ESS ≥ 2 were related to worse olfactory outcomes, probably due to iatrogenic damage. No correlation was found between hematic eosinophils and outcomes. AEs were reported by 12.4% of patients and 2.2% had to discontinue dupilumab. Weight gain was an emergent AE (0.8%), probably related to the restored sense of smell and taste. Non-responders were 3.5% and they were switched to systemic steroid, ESS, or another biologic. CONCLUSION: Despite some differences in prescription criteria between countries, dupilumab was demonstrated to be effective even in the real-life scenario. However, emerging AEs and possible unknown long-term AEs of a likely lifelong therapy should be considered.

Cystic fibrosis-related chronic rhinosinusitis: the key role of a comprehensive evaluation in the era of highly effective modulator therapy.

BACKGROUND: Chronic rhinosinusitis (CRS) is prevalent in cystic fibrosis (CF), significantly affecting quality of life. The introduction of CFTR modulators, including elexacaftor-tezacaftor-ivacaftor (ETI), offers promise for improving sinonasal outcomes. METHODS: We conducted a retrospective cohort multicenter study analyzing electronic medical records of 45 adult CF patients with CRS, predominantly heterozygous for the ΔF508 mutation, treated with ETI between January 2018 and December 2023. Assessments included Sinonasal Outcome Test 22 (SNOT-22), Nasal Polyp Score (NPS), modified Lund-Kennedy Score (mLKS), Lund-Mackay Score (LMS), and olfactory function using smell loss visual analog scale (VAS) and Sniffin' Sticks identification test (SSIT). RESULTS: After 12 months of ETI therapy, significant improvements were observed in pulmonary function parameters (FEV1, FVC), CRS severity scores (SNOT-22, NPS, mLKS), radiological findings (LMS), and olfactory function. Subgroup analysis suggested enhanced efficacy in patients with prior endoscopic sinonasal surgery. CONCLUSIONS: ETI therapy demonstrates comprehensive improvements in CRS and olfactory function in CF patients, highlighting the potential of CFTR modulators in managing sinonasal manifestations.

Effects of Mepolizumab in the treatment of type 2 CRSwNP: a real-life clinical study.

PURPOSE: Mepolizumab was recently approved for treating Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) unresponsive to standard treatment or recurring after endoscopic sinus surgery (ESS). To date, few studies have assessed Mepolizumab's efficacy in severe type-2 CRSwNP. Our study aimed to analyze sinonasal outcomes in type-2 CRSwNP patients treated with 100 mg Mepolizumab administered subcutaneously every four weeks. METHODS: We conducted a retrospective study of patients with severe, recalcitrant CRSwNP treated with Mepolizumab. Demographic and clinical characteristics were collected, including age, sex, and comorbidities such as asthma, nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (NERD), and allergic rhinitis (AR), as well as the number of previous ESS procedures and the interval since the last one. Patients were evaluated at baseline and after one year for blood eosinophil count, nasal polyp score (NPS), modified Lund-Kennedy score (mLKS), olfactory function (using a VAS scale and a 16-item Sniffin' identification test), SNOT-22, and sinus opacification on CT scans. The need for rescue ESS or systemic corticosteroids (SCS), response to treatment, and side effects were also recorded. RESULTS: Data from 27 patients were collected. After one year, all scores showed significant improvement. NERD was the only factor associated with a less favorable improvement in olfactory function. There were no side effects reported, although 2 patients discontinued Mepolizumab as they were considered "non-responders." CONCLUSIONS: Mepolizumab is safe and effective in reducing the clinical, endoscopic, and radiological burden of disease, as well as in decreasing the need for salvage ESS or systemic steroids.

High proportion of inflammatory CD62Llow eosinophils in blood and nasal polyps of severe asthma patients.

BACKGROUND: In mice models, eosinophils have been divided into different subpopulations with distinct phenotypes and functions, based on CD62L and CD101 patterns of membrane expression. Limited data are available in humans. OBJECTIVE: To investigate eosinophils subpopulations in peripheral blood (PB) and nasal polyp tissue (NP) from severe eosinophilic asthma (SEA) patients plus concomitant chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: We recruited 23 SEA patients (14 with CRSwNP); as controls, we enrolled 15 non-severe asthma patients, 15 allergic rhinitis patients without asthma and 15 healthy donors. Eosinophils were isolated from PB and NP and analysed by FACS. Eotaxin-3 and eotaxin-1 mRNA expression in NP tissue was also evaluated. RESULTS: A significantly higher percentage of circulating CD62Llow cells was observed in SEA, as compared with controls, expressing higher levels of CCR3, CD69 and lower levels of CD125 (IL-5R), CRTH2, CD86 and CD28 in comparison with CD62Lbright cells. In NP, eosinophils showed a high proportion of CD62Llow phenotype, significantly greater than that observed in PB. Surface expression of IL-3R, IL-5R, CD69 and CD86 was significantly higher in CD62Llow eosinophils from NP than in those from blood. Moreover, eotaxin-3 mRNA expression positively correlated with the percentage of CD62Llow cells in NP. CONCLUSION: Two different eosinophil subphenotypes can be identified in blood and NP of SEA patients, with a preferential accumulation of CD62Llow inflammatory cells in NP.

Blood CD62Llow inflammatory eosinophils are related to the severity of asthma and reduced by mepolizumab.

BACKGROUND: Eosinophils have been divided into different subpopulations with distinct phenotypes based on CD62L expression. No data are available regarding the correlation between eosinophils subphenotypes and clinical severity of asthma, as well as the effect of anti-IL-5 therapy on these cells. The study investigates the correlation between blood CD62Llow inflammatory eosinophils (iEos) and clinical severity of severe eosinophilic asthma (SEA) and evaluates the impact of mepolizumab on iEos. METHODS: 112 patients were screened and were divided in two groups: biological-naive (n = 51) and biological-treated patients (n = 61). The Biological-naive patients were analyzed before treatment (Group A) and 19 out of 51 patients, were longitudinally analyzed before and after treatment with mepolizumab 100 mg s.c/4 weeks (Group B); 32 patients were excluded because they were being treated with other biological therapies. Blood eosinophils were analyzed by FACS and correlated with clinical scores. In vitro effect of IL-5 and mepolizumab on CD62L expression was assessed. RESULTS: A significant correlation between blood CD62Llow cells and clinical scores of asthma and nasal polyps, as well as the number of asthma exacerbations in the last year was shown in untreated patients. In longitudinally studied patients we observed a marked reduction of CD62Llow cells paralleled by an increase in the proportion of CD62Lbright cells, associated with clinical improvement of asthma control. In vitro, CD62L expression on eosinophils is modulated by IL-5 and anti-IL-5. CONCLUSION: A positive correlation between CD62Llow iEos and the baseline clinical features of SEA with CRSwNP was shown. Furthermore mepolizumab restores the healthy balance among eosinophils sub-phenotypes in SEA patients.

Oncological and functional impact of adjuvant treatments after open partial laryngeal surgery: a systematic review of the literature and a meta-analysis.

BACKGROUND: The oncological and functional role of postoperative radiotherapy (PORT) after open partial laryngeal surgery (OPLS) remains debatable. METHODS: A systematic review and a meta-analysis of the literature were conducted according to the PRISMA guidelines. Outcomes of patients receiving OPLS with and without PORT for laryngeal cancer were summarized. RESULTS: In the 10 studies that were included in the meta-analysis, no significant difference emerged in terms of pooled overall survival between OPLS patients who did and who did not receive PORT (- 0.3%, 95% CI - 5.4 to 4.9%, p = 0.922). Only one study showed a significantly higher incidence of complications in the PORT cohort. CONCLUSIONS: PORT may apparently be performed after OPLS in face of adverse postoperative features without an increased risk of toxicities affecting the neolarynx. Because of the limitations in the available literature, the oncological and functional effects of PORT in this setting needs to be prospectively assessed to strengthen the evidence of this treatment strategy for laryngeal cancer.

Otoendoscopy in the era of narrow-band imaging: a pictorial review.

PURPOSE: Otoendoscopy represents the initial non-invasive diagnostic cornerstone for external and middle ear disorders. Recently, new techniques of enhanced imaging such as narrow-band imaging (NBI) have been introduced but their role as a potential aid in otological practice remains unproven. In this pictorial review, we want to present the potential application of this endoscopic method, highlight its limitations, and give some hints regarding its future implementation. METHODS: Representative cases of external and/or middle ear pathologies were selected to illustrate the role of NBI in this regard. RESULTS: NBI may represent a useful aid in the otological work-up, in the differential diagnosis of ear tumor-like masses, and, possibly, in the prognosis of tympanic perforations. For other ear disorders, instead, this technique does not seem to add anything to the standard clinical practice. CONCLUSIONS: NBI might prove useful in the assessment of selected external and middle ear disorders but its role must be prospectively validated.

Rhino-oropharingeal osteoradionecrotic soft-tissue and bony defect reconstruction with submental artery island flap: a case report.

BACKGROUND: The submental artery island flap is widely used in head and neck reconstruction, since it is easy and quick to harvest, and it can be successfully used for the coverage of perioral, intraoral and facial defects. We used this technique for the reconstruction of a complex soft-tissue and bony defect of rhino-oropharinx. CASE REPORT: Osteoradionecrosis of rhino-oropharingeal posterior wall with C2 necrotic body exposure occurred in a 77-year-old woman. After the failure of reconstruction with a Hadad-Bassagasteguy flap, a submental island flap with cervical spine stabilization was planned to be performed in a one-stage operation. The anterior arc of C1 and odontoid process of C2 were removed and, according to the defect size, a submental island flap was designed in an elliptical fashion. The flap was rotated 180° and tunnelized under the left parapharingeal-prevertebral space, then it was positioned in the rhino-oropharinx and fixed with reabsorbable sutures. The donor site was closed primarily. No peri- or post-operative complications occurred, neither in the recipient nor in the donor-site. At the latest follow-up, 15 months postoperatively, the patient was able to speak without any impairment and started swallowing rehabilitation with good results and an aesthetically satisfactory outcome. CONCLUSION: The submental island flap may be a reliable and versatile flap for reconstruction of head and neck defects, even though in the rhino-oropharingeal posterior wall.

Extracellular vesicles miR-210 as a potential biomarker for diagnosis and survival prediction of oral squamous cell carcinoma patients.

BACKGROUND: The identification of early diagnostic and prognostic biomarkers in oral squamous cell carcinoma (OSCC) is an unmet clinical need. We hypothesized that extracellular vesicles miR-210 expression (EV-miR-210) could be a potential biomarker for OSCC diagnosis and follow-up. METHODS: The expression of EV-miR-210 was measured in the plasma of OSCC patients (n = 30) and compared to that of controls (n = 14). RESULTS: The median EV-miR-210 expression was significantly higher in OSCC patients compared to controls who had often, undetectable levels (p < 0.0001). We performed receiver operating characteristic (ROC) analysis for discriminating OSCC cases from controls. EV-miR-210 yielded an area under the curve (AUC) of 0.9513 with sensitivity 92.3% and specificity 86.6%. Kaplan-Meier curves indicated that high EV-miR-210 expression was associated with worse 3 years' survival (p < 0.05). Cox regression hazard model indicated that high EV-miR-210, G2, and G3 grading and pathological nodal status (pN)>1 were independent predictors of worse survival in OSCC patients. CONCLUSION: These preliminary data suggest that EV-mir-210 may be a novel diagnostic and prognostic biomarker in OSCC.

A practical overview of CT and MRI features of developmental, inflammatory, and neoplastic lesions of the sphenoid body and clivus.

The sphenoid bone is an unpaired bone that contributes to the formation of the skull base. Despite the enormous progress in transnasal endoscopic visualisation, imaging techniques remain the cornerstones to characterise any pathological condition arising in this area. In the present review, we offer a bird's-eye view of the developmental, inflammatory, and neoplastic alterations affecting the sphenoid body and clivus, with the aim to propose a practical diagnostic aid for radiologists based on clinico-epidemiological, computed tomography, and magnetic resonance imaging features.

The prognostic role of IL-10 in non-severe COVID-19 with chemosensory dysfunction.

OBJECTIVES: Olfactory and gustatory dysfunction (OD/GD) are now recognized as typical symptoms of COVID-19 infection. However, their pathogenesis remains unclear and no clear prognostic factors have been identified. We have analyzed a cohort of mild/moderate hospitalized patients to identify possible clinical or immunological predictors of recovery from OD/GD. METHODS: Clinical and biological parameters were reviewed along with associated comorbidities. Chemosensory Complaint Score was administered on admission and 30 days after the first negative swab. Unpaired Wilcoxon and chi-squared tests were used to compare the variables in the patients who recovered versus those who did not. RESULTS: From a cohort of 119 hospitalized patients, 43 (36%) reported OD/GD on admission. 60.6% had a full recovery from OD and 69.2% from GD. Only the concentration of IL-10 on admission emerged as significantly associated with recovery of taste (p = 0.041) while allergic respiratory disease was more prevalent in the group who did not recover from OD (p = 0.049) and GD (p = 0.007). CONCLUSION: These findings suggest that COVID-19 associated OD/GD is an inflammatory-mediated condition and that clinical and immunological parameters could predict the evolution of these symptoms.

Epidemiological analysis of a COVID-19 outbreak associated with an infected surgeon.

Control of the novel COronaVIrus Disease-2019 (COVID-19) in a hospital setting is a priority. A COVID-19-infected surgeon performed surgical activities before being tested. An exposure risk classification was applied to the identified exposed subjects and high- and medium-risk contacts underwent active symptom monitoring for 14 days at home. All healthcare professionals (HCPs) were tested for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) at the end of the quarantine and serological tests were performed. Three household contacts and 20 HCPs were identified as high- or medium-risk contacts and underwent a 14-day quarantine. Fourteen HCPs and 19 patients were instead classified as low risk. All the contacts remained asymptomatic and all HCPs tested negative for SARS-CoV-2. About 25-28 days after their last exposure, HCPs underwent serological testing and two of them had positive IgM but negative confirmatory swabs. In a low COVID-19 burden area, the in-hospital transmission of SARS-CoV-2 from an infectious doctor did not occur and, despite multiple and frequent contacts, a hospital outbreak was avoided. This may be linked to the adoption of specific recommendations and to the use of standard personal protective equipment by HCPs.

The impact of the COVID-19 pandemic on the quality of life of head and neck cancer survivors.

BACKGROUND: Head and neck cancer (HNC) survivors are particularly vulnerable to the deleterious consequences of lockdown and social distancing. The psychosocial effects of the COVID-19 pandemic on this group are still unknown, and we want to explore how their quality of life (QoL) has changed in this unique situation. MATERIALS AND METHODS: An online survey, composed of pandemic-specific items, plus the EORTC QLQ-C30, was administered to a cohort of HNC survivors. Using previously published reference values as a control group, we have evaluated the impact of the pandemic on their QoL. We have also explored the differences between those who had received a total laryngectomy (LP, laryngectomized population) vs other HNC patients, in order to assess the role of tracheostomy in this regard. RESULTS: One hundred and twenty-one HNC patients completed the survey. The scores of the physical (80.5 vs 85, p = 0.028), role (78 vs 84, p = 0.030), and emotional functioning (76 vs 81, p = 0.041) were significantly different in the two groups, with worse functioning in our patients. Comparing LP with the other HNC patients, social (76.6 vs 88.9, p = 0.008) and physical functioning (75.5 vs 86.1, p = 0.006) were significantly worse in the former group. LP also reported a greater perception that others are afraid to be close to them (1.67 vs 1.32, p = 0.020). No differences were found between LP with and without voice prosthesis. CONCLUSIONS: Our results show how HNC patients are at high risk for a worsening in QoL because of the ongoing COVID-19 global pandemic.

Sudden olfactory loss as an early marker of COVID-19: a nationwide Italian survey.

PURPOSE: The presence of many asymptomatic COVID-19 cases may increase the risks of disease dissemination, mainly for physicians. There are numerous reports on the frequent findings of sudden anosmia or hyposmia, before or at the same time of the typical COVID-19 symptoms onset. The aim of this study was to verify the association of olfactory impairment and COVID-19, providing a basis for subsequent research in the field of COVID-19 clinical heterogeneity. METHODS: We developed a 15-item online questionnaire on "Sudden Olfactory Loss (SOL) and COVID-19" that was administered during March 2020 to Italian general practitioners registered to a social media group. RESULTS: One hundred and eighty responses were received. SOL was identified as a significant sign of infection in COVID-19 patients, mainly aged between 30 and 40 years, even in the absence of other symptoms. SOL was present as an initial symptom in 46.7% of subjects, and in 16.7%, it was the only symptom. Among the COVID-19 confirmed cases, SOL occurred as the only symptom in 19.2% of patients. CONCLUSION: SOL could represent a possible early symptom in otherwise asymptomatic COVID-19 subjects. Subjects affected by SOL should be considered as potential COVID-19 cases. LEVEL OF EVIDENCE: 4.

The Umbrella Technique for the Closure of Cerebrospinal Fluid Fistula.

ABSTRACT: The diagnosis and management of cerebrospinal fluid (CSF) rhinorrhea remains an important challenge in the field of rhinology. In this study, the authors want to propose a technique for transnasal endoscopic closure of CSF fistulas, tested for the first time on 2 adult fresh cadaveric specimens. The authors think that the use of a device similar to the umbrella device, used to close cardiac atrial defects, may also be valid for the closure of defects at the level of the anterior skull base.

A New Solution for Routine Endoscopic Aerosol-Generating Procedures (AGPs) in the COVID-19 Pandemic.

INTRODUCTION: There is urgent need to find a swift and cheap way to safely perform routine endoscopic procedures during the otolaryngological and anesthesiological practice. We want to share our experience of a novel device, inspired by the pediatric head box experience. MATERIALS AND METHODS: Five otolaryngologists and four anesthesiologists were asked to visualize the glottic plane by using the device. A total of 15 attempts was allowed to reach the vocal folds within 60 seconds after entering the box. Student's t-test for unpaired samples was used to compare groups. RESULTS: Transnasal laryngoscopy through our endobox could be successfully performed by all the physicians involved and the mean number of attempts before visualizing and passing the glottis for the first time was 2.8 (range 1-5) in the otolaryngologists' group versus 3.2 (range 1-6) in the anesthesiologists' group (P=0.583). Out of the 15 attempts, the group of otolaryngologists reached the glottis 10.2 times, on average, against 9.7 in the other group (P=0.692). CONCLUSIONS: Our endobox seems a practical and feasible strategy to control droplets diffusion during standard ear, nose, and throat and anesthesiological practice.

Outcomes of endoscopic sinus surgery in adult lung transplant patients with cystic fibrosis.

PURPOSE: Cystic Fibrosis (CF) is the most common autosomal recessive disease in Caucasian population. Due to its pathological mechanism, chronic rhino sinusitis (CRS) associated or not with nasal polyposis usually occurs in adults and affects close to one-half of all CF patients. The goal of our work was to evaluate the impact of Endoscopic Sinus Surgery (ESS) in the quality of life (QoL) of the CF patients and demonstrate an improvement of the functional outcomes in the patients underwent the surgical procedure rather than in the not treated ones, particulary in lung transplant patients. METHODS: We studied 54 adult patients affected by CF. Lund-Kennedy, Lund-Mackay scores, and SNOT-22 were analysed. 14 had lung transplant and 9 had both lung tranplant and ESS procedures. RESULTS: 22 (40.7%) out of 54 CF patients underwent ESS. This group presented more likely complaints consistent with CRS. Lund-Kennedy and Lund-Mackay scores appeared higher in the ESS group: 10 (range of 6-12) and 15 (range of 12-20), respectively. SNOT-22 showed median values for non-ESS and ESS group of 20 (range of 3-68) and 40 (range of 10-73), respectively. CONCLUSIONS: ESS represents the best option to improve clinical QoL of CF patients who do not response to conventional medical therapy, with a stabilization of respiratory function after transplantation.