Dupilumab in the treatment of severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP): A multicentric observational Phase IV real-life study (DUPIREAL)

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

Cerebrospinal fluid leak repair: utility of intrathecal fluorescein for correct topographic identification of the skull base defects

Background: In the management of cerebrospinal fluid (CSF) leak the identification of the exact discharge spot is paramount. This can represent a challenge for the radiologist and the surgeon. In the present study, we analyzed a series of patients affected by endonasal CSF leak who underwent endoscopic surgical reconstruction aided by the use of intrathecal fluorescein (ITF). The purpose of this work is to assess the efficacy of intraoperative ITF in addition to computed tomography (CT) scan and magnetic resonance imaging (MRI) for correct topographic localization of the CSF leak. Methods: Eighty-three patients were enrolled in the study. The main outcome was the concordance between the supposed radiological defect site and the actual one seen intraoperatively. The recurrence free survival (RFS) was evaluated as secondary outcome. Results: ITF better defined the defect site allowing a change in the treatment in 21 cases (25.3%), in which a non-concordance was observed between the suspected radiological site and the actual surgical one. Good agreement was found between the specific topographic localization (k=0.737, p<0.0001), whereas fair agreement was observed considering the side of the defect (k=0.362, p=0.0009) and correct identification of multiple sites (k=0.044, p=0.666). The 10-year 96% estimate of RFS confirmed the correct repair of the fistula site in most of the cases. Conclusions: Our data demonstrate the utility and safety of intraoperative ITF for management of patients affected by endonasal CSF leak. ITF improved the topographical diagnosis of the leak site, ensuring the best target reconstruction and very low recurrence rate

SmartProbe: a bioimpedance sensing system for head and neck cancer tissue detection

This study presents SmartProbe, an electrical bioimpedance (EBI) sensing system based on a concentric needle electrode (CNE). The system allows the use commercial CNEs for accurate EBI measurement, and was specially developed for in-vivo real-time cancer detection. Considering the uncertainties in EBI measurements due to the CNE manufacturing tolerances, we propose a calibration method based on statistical learning. This is done by extracting the correlation between the measured impedance value |Z| and the material conductivity \u3c3 of a group of reference materials. By utilizing this correlation, the relationship of \u3c3 and |Z| can be described as a function and reconstructed using a single measurement on a reference material of known conductivity. This method simplifies the calibration process, and is verified experimentally. Its effectiveness is demonstrate by results that show less than 6% relative error. An additional experiment is conducted for evaluating the system's capability to detect cancerous tissue. Four types of ex-vivo human tissue from the head and neck region, including mucosa, muscle, cartilage and salivary gland, are characterized using SmartProbe. The measurements include both cancer and surrounding healthy tissue excised from 10 different patients operated for head and neck cancer. The measured data is then processed using dimension reduction and analyzed for tissue classification. The final results show significant differences between pathologic and healthy tissues in muscle, mucosa and cartilage specimens. These results are highly promising and indicate a great potential for SmartProbe to be used in various cancer detection tasks

Electric Bioimpedance Sensing for the Detection of Head and Neck Squamous Cell Carcinoma

The early detection of head and neck squamous cell carcinoma (HNSCC) is essential to improve patient prognosis and enable organ and function preservation treatments. The objective of this study is to assess the feasibility of using electrical bioimpedance (EBI) sensing technology to detect HNSCC tissue. A prospective study was carried out analyzing tissue from 46 patients undergoing surgery for HNSCC. The goal was the correct identification of pathologic tissue using a novel needle-based EBI sensing device and AI-based classifiers. Considering the data from the overall patient cohort, the system achieved accuracies between 0.67 and 0.93 when tested on tissues from the mucosa, skin, muscle, lymph node, and cartilage. Furthermore, when considering a patient-specific setting, the accuracy range increased to values between 0.82 and 0.95. This indicates that more reliable results may be achieved when considering a tissue-specific and patient-specific tissue assessment approach. Overall, this study shows that EBI sensing may be a reliable technology to distinguish pathologic from healthy tissue in the head and neck region. This observation supports the continuation of this research on the clinical use of EBI-based devices for early detection and margin assessment of HNSCC

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

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

Practical recommendations for managing severe chronic rhinosinusitis with nasal polyps in the era of biologics

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 recom- mendations for clinical practice. Results. ENTs working in rhinology centres changed their practices coinciding with the advent of biologics. CRSwNP evaluations have be- come more complex because they involve diagnostic confirmation, determining the patients’ immunologic profile, and other factors. We ob- served 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

PRACTICAL RECOMMENDATIONS FOR MANAGING SEVERE CHRONIC RHINOSINUSITIS WITH NASAL POLYPS IN THE ERA OF BIOLOGICS

Objective: we conducted a national survey to understand how rhinology practice 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 survey’s results 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 heterogeneous 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 practices and improve care