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.

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

BACKGROUND: Parathyroid hormone-related peptide (PTHrP) overexpression and poor patient outcome have been reported for many human tumors, but no studies are available in laryngeal cancer. Therefore, we studied the expression of PTHrP and its receptor, parathyroid hormone-related peptide receptor type 1 (PTH1R), in primary locally advanced laryngeal squamous cell carcinomas (LALSCC) also in relation to the clinical outcome of patients. METHODS: We conducted a retrospective exploratory study, using immunohistochemistry, on PTHrP, PTH1R and HER1 expressions in LALSCC of 66 patients treated with bio-radiotherapy with cetuximab. RESULTS: The expressions of PTHrP and PTH1R in LALSCC were associated with the degree of tumor differentiation (p = 0.01 and 0.04, respectively). Poorly differentiated tumors, with worse prognosis, expressed PTHrP at nuclear level and were PTH1R negative. PTHrP and PTH1R were expressed at cytoplasmic level in normal larynx epithelium and more differentiated laryngeal cancer cells, suggesting an autocrine/paracrine role of PTHrP in squamous cell differentiation of well differentiated tumors with good prognosis. Eighty-one percent HER1 positive tumors expressed PTHrP (p < 0.0001), mainly at nuclear level, consistent with the known up-regulation of PTHrP gene by HER1 signaling. In multivariable analyses, patients with PTHrP positive tumors had a higher relative risk of relapse (HR = 5.49; CI 95% = 1.62-22.24; p = 0.006) and survival (HR = 8.21; CI 95% = 1.19-105.00; p = 0.031) while those with PTH1R positive tumors showed a lower relative risk of relapse (HR = 0.18; CI 95% = 0.04-0.62; p = 0.002) and survival (HR = 0.18; CI 95% = 0.04-0.91; p = 0.029). CONCLUSIONS: In LALSCC nuclear PTHrP and absence of PTH1R expressions could be useful in predicting response and/or resistance to cetuximab in combined therapies, contributing to an aggressive behavior of tumor cells downstream to HER1.

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

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.

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

BACKGROUND: Compared to the other members of human epidermal growth factor family receptors (HER), the role of HER3 has not been well defined in laryngeal cancer. The predictive and prognostic role of HER3 has been the focus of clinical attention but the research findings are contradictory, especially in laryngeal squamous cell carcinoma (LSCC). The variable localization of HER3 within cancer cells and the role of HER3 in primary and acquired resistance to HER1-targeted therapies remain unclear. METHODS: We performed a retrospective analysis of two cohorts of 66 homogeneous consecutive untreated primary advanced LSCC patients, in which co-expression of HER1, HER2 and HER3 receptors was investigated by semi-quantitative immunohistochemistry. The association of their pattern of expression with survival was evaluated by Kaplan-Meier and Cox's proportional hazard analyses. Multivariable Cox proportional hazards models were developed to predict median 2- and 3-year RFS and 2.5- and 5-year OS. The Akaike information criterion technique and backwards stepwise procedure were used for model selections. The performance of the final Cox models was assessed with respect to calibration and discrimination. RESULTS: Immunohistochemical labeling for HER1 and HER2 was localized both in the cell membrane and in the cytoplasm, while HER3 labeling was observed both in the cell cytoplasm and in the nucleus. HER3 expression was inversely correlated with HER1 positivity. The expression patterns of HERs were associated with tumor differentiation. In both cohorts of patients, HER1 expression was associated with reduced relapse-free (RFS) and overall survival (OS). In HER1 positive tumors, the co-expression with nuclear HER3 was associated with better RFS and OS, compared with HER3 negative tumors or tumors expressing HER3 at cytoplasmic level. HER3 expressing tumors had a higher Geminin/MCM7 ratio than HER3 negative ones, regardless of HER1 co-expression. Multivariable analyses identified age at diagnosis, tumor site, HER1, HER3 and age at diagnosis, tumor stage, HER1, HER3, as covariates significantly associated with RFS and OS, respectively. Bootstrapping verified the good fitness of these models for predicting survivals and the optimism-corrected C-indices were 0.76 and 0.77 for RFS and OS, respectively. CONCLUSIONS: Nuclear HER3 expression was strongly associated with favourable prognosis and allows to improve the prognostic stratification of patients with HER1 positive advanced LSCC carcinoma.

How Long Is Otosclerosis Surgery Effective? Hearing Results after a 22-Year Follow-Up.

INTRODUCTION: Stapes surgery is a safe procedure, with favourable hearing outcome. The objective of the study is to assess the long-term hearing results, addressing the bone conduction (BC) decay and the need for hearing aids in otosclerosis patients. METHODS: We enrolled patients who underwent stapes surgery by means of stapedectomy or stapedotomy between 1991 and 2001. All enrolled patients underwent pure-tone audiometry (PTA) between September 2017 and June 2018. A set of questions was administered to record the prevalence of subjective symptoms and the need for hearing aids. RESULTS: Seventy patients were enrolled for a long-term evaluation; 37 patients underwent bilateral surgery; therefore, 107 ears were included in the analysis. The average follow-up period was 22 years. No statistically significant difference was found between early and late post-operative air conduction (AC) PTA (41 vs. 49 dB; p > 0.05) nor between early and late post-operative BC-PTA (29 vs. 37 dB; p > 0.05). A significant difference was observed for AC at 8 kHz (65 vs. 78 dB; p < 0.05) and BC at 2 and 4 kHz (28 vs. 40 dB and 45 vs. 58 dB, respectively; p < 0.05). CONCLUSIONS: This is, to our knowledge, the longest mean follow-up time in the literature. A mild decrease in both AC and BC threshold can be expected and the sensorineural decay is more pronounced on the high frequencies. The subjective hearing symptoms and overall sound perception are satisfactory.

The usefulness of the IMAP propeller flap for trachea and tracheostome reconstruction after resection of parastomal recurrence of squamous cell carcinoma following salvage total laryngectomy.

PURPOSE: Parastomal recurrence of squamous cell carcinoma (SCC) with tracheal involvement following salvage total laryngectomy after prior concurrent chemoradiotherapy is one of the most insidious challenges in head and neck surgery because a complex reconstruction is often required for covering a large area of skin loss, filling the dead space beneath, tracheal reconstruction and suspension, and tracheostome resurfacing. The aim is to describe our experience with the internal mammary artery perforator (IMAP) propeller flap for tracheal and tracheostome reconstruction and neck resurfacing after parastomal and cervical trachea resection, especially for suspension and anchoring the stump of the residual distal trachea to the island flap itself. METHODS: We describe IMAP flap reconstruction after resection of parastomal recurrence of SCC requiring cervical trachea resection in five patients between January 1, 2005 and August 30, 2019. RESULTS: IMAP propeller flap was successfully used for reconstruction after complex resection of parastomal recurrence of SCC with cervical trachea involvement in all cases. The mean length and width were, respectively, 16.8 cm (range 13-23) and 6.9 cm (range 5.5-8). We did not report complications of both the donor and the recipient site. Pharyngo-cutaneous or tracheoesophageal fistulas and wound dehiscence were not observed. CONCLUSIONS: to the best of our knowledge, this is the first report about the use of the IMAP propeller flap in this more complex clinical setting and we provide the message that this surgical procedure is worthy of consideration.

Narrow Band Imaging for lingual tonsil hypertrophy and inflammation, in laryngo-pharyngeal reflux disease.

PURPOSE: The objective of this study is to analyse the relationship between the endoscopic signs of laryngo-pharyngeal reflux, the lingual tonsil hypertrophy (LTH) and its inflammation, adopting Narrow Band Imaging (NBI) technology. METHODS: We enrolled, as cases, patients with clinical diagnosis of laryngopharyngeal reflux disease (LPRD), a Reflux Symptom Index (RSI) ≥ 13, and a Reflux Finding Score (RFS) ≥ 7. Controls were enrolled among patients who underwent the same transnasal endoscopy, equipped with NBI, with a RSI < 13 and a RFS < 7. Nasopharynx, Lingual Tonsils (LT), Hypopharynx and Larynx were evaluated by two experienced otolaryngologists, who calculated the Reflux Finding Scale (RFS) score and focused their attention on the base of the tongue, observing its surface with NBI technology. RESULTS: 82 patients with diagnosis of laryngopharyngeal reflux were enrolled as cases. Mean RFS was 11.7 (SD = 2.9). As controls, we enrolled 80 patients. Mean RFS was 2.7 (SD = 1.63). We found that RFS positivity was associated with a significant increase in LT dimension (2.5 vs 1.1, p < 0.001), with a higher LT crypt inflammation grading (1.8 vs 0.09, p < 0.001) and with a higher Roman Cobblestone pattern grading (1.48 vs 0.11, p < 0.001). A significant correlation between the crypt inflammation and the hyperemia subscore of RFS was present (r = 0.696, p < 0.0001), while it was not possible to find a correlation between crypt inflammation and either diffuse laryngeal edema (r = 0.166, p = 0.135) and posterior commissure hypertrophy (r = 0.089, p = 0.427). CONCLUSIONS: NBI allowed us to identify endoscopically the presence of enlarged lingual tonsil, crypt inflammation and superficial mucosal changes, in patients affected by LPRD. LEVEL OF EVIDENCE: 2 (prospective, case-control study).

Late Prevalence of Typical and Atypical Symptoms of Frey's Syndrome after Parotidectomy for Benign Tumor.

BACKGROUND: The treatment of choice for tumors located in the parotid gland is surgery. Nevertheless, postoperative complications are not infrequent. Regardless of the type of surgical procedure, the most common complication is Frey's syndrome (FS). Traditionally, FS includes unilateral gustatory sweating and flushing of the facial skin lining the parotid compartment. Recent research describes atypical discomfort associated with FS. The aim of this study was to assess the late prevalence and severity of both usual and atypical symptoms after parotidectomy for benign tumors. METHODS: We conducted a cross-sectional study involving 86 subjects who underwent superficial parotidectomy at least one year before the study. The questionnaire included the sweating-flushing-itch-paresthesia-pain (SFIPP) Frey scale supplemented by specific questions about symptoms. RESULTS: Sixty-seven out of eighty-six (77.9%) cases reported almost one symptom. The most frequent symptom was itch (36/67-53.7%), followed by pain (35/67-52.2%), while 28/67 (41.8%) subjects complained of atypical symptoms without flushing or sweating. A desire to treat the discomfort was reported by 50/67 (74.6%) subjects. CONCLUSIONS: Late postparotidectomy local discomfort is not infrequent and includes both usual and "unusual" symptoms almost equally. Our results suggest the importance of informing patients about the occurrence of the syndrome and the available treatment options during pre- and postoperative counseling.

Correlation between inflammatory biomarkers and disease control in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) may have a heterogeneous response to medical/surgical treatments based on endotypes. Data correlating biomarkers and severity of the disease are lacking. We aimed to determine if IL-5 and calprotectin may be useful in defining severity of disease and identifying uncontrolled patients. METHODS: This was a case-control study including 81 patients with diffuse CRSwNP who underwent at least one previous surgery and treated with intranasal steroids. We enrolled 39 uncontrolled patients (SNOT-22 ≥ 40 and two or more cycles of systemic corticosteroids in last year) (Group A) and 42 controlled one (SNOT-22 < 40 and less than two cycles of systemic corticosteroids in last year) (Group B). We analyzed IL-5 and calprotectin in both nasal secretions and nasal polyp tissue. RESULTS: Calprotectin and IL-5 were significantly higher in Group A in both secretions and tissue, and the higher the number of previous surgeries, the higher the levels detected in nasal secretions. At univariate analyses, smoking, asthma, non-steroidal anti-inflammatory drugs-exacerbated respiratory disease (NSAID-ERD), blood eosinophilia, neutrophils, and eosinophils at nasal cytology were significantly associated with uncontrolled disease. Multivariate analyses showed that asthma, NSAID-ERD, and IL-5 in nasal secretion/polyp tissue were significantly related to the risk of uncontrolled disease. CONCLUSIONS: Our data suggest that asthma, NSAID-ERD, and IL-5 in nasal secretions/tissue may be helpful to identify more severe patients, as they are related to the risk of uncontrolled disease. Nonetheless, high levels of calprotectin and neutrophilia were also observed in uncontrolled patients, especially after multiple surgeries.

Validity of Italian adaptation of the Vanderbilt Paediatric Dizziness Handicap Inventory.

Objective: The paediatric caregiver version of the Dizziness Handicap Inventory (DHI-PC) questionnaire is a useful Quality of Life (QoL) evaluation instrument for children experiencing dizziness, vertigo or unsteadiness. Its English version has been validated for use with a paediatric population between 5 and 12 years of age. The aim of this work is to validate the DHI-PC into Italian for both patient assessment and appropriate rehabilitative treatment planning. Materials and methods: Cross-cultural adaptation of the DHI-PC was performed using standard techniques. Items of the original questionnaire were translated into Italian by two bilingual investigators. Two native English speakers carried out a back translation of the new version that was compared with the original to check that they had the same semantic value. A pre-final version was obtained by an expert committee and was applied in a pilot test. Results: A total of 42 patient caregivers completed the final adapted questionnaire twice with an interval of 2 weeks. Internal consistency was excellent, with Cronbach's alpha = 0.95. Conclusions: Our study showed evidence that the Italian version of DHI-PC is a valid and reliable tool to quantify the degree of dizziness handicap and its application is recommended.

How to manage recurrences after surgery in CRSwNP patients in the biologic era: a narrative review.

Objective: This narrative review analyses factors affecting recurrence of Chronic rhinosinusitis with nasal polyps (CRSwNP) after surgery, such as type, extension and completeness of endoscopic sinus surgery (ESS). We also described new implications in the management of recurrences after the advent of biologics. Methods: We identified four topics: definition of disease state; factors linked to recurrence of polyps; evaluation and management of recurrence in clinical practice. Results: We analysed the differences between exacerbation and recurrence, as well as the concept of "controlled disease". We focused on potential predictors of recurrence after ESS, such as type 2 inflammation, asthma, aspirin-exacerbated respiratory disease, incomplete initial surgery and lack of adherence to long-term post-operative local corticosteroids. We discussed the new aspects of diagnosis and treatment of recurrences after surgery, summarising our suggestions in a detailed algorithm for practical management of patients with recurrent disease. Conclusions: The results emphasised the importance of accurate evaluation of patients with CRSwNP recurrence, focusing on the reasons of failure and risk of disease progression, in order to guide personalised interventions. It is crucial to define the concept of appropriate surgery, which affects the choice between starting a biologic or repeating surgery.

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 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.

Elective Neck Dissection during Salvage Total Laryngectomy: Personal Experience.

The role of elective neck dissection during salvage surgery in patients with a clinically negative neck (cN0) is still discussed. The main objective of this work was to estimate the prevalence and predictive factors of occult neck nodes metastasis; we therefore aimed to evaluate the survival rate and the main oncologic outcomes of cN0 patients who underwent salvage total laryngectomy and elective bilateral neck dissection. In this retrospective observational study, we enrolled 80 cN0 patients affected by recurrent laryngeal cancer and who underwent salvage total laryngectomy and bilateral selective elective neck dissection. Several parameters were collected in order to find prognostic factors; finally, postoperative complications were reviewed and survival analysis was performed. Occult lymph node metastases were reported in 18 out of 80 patients (22.5%). Significant statistical correlation between lymphovascular invasion (p = 0.007), perineural invasion (p = 0.025) and occult nodal metastasis was found. Other variables (glottic subsite of recurrence, clinical T, pathological T, previous chemotherapy) were not significantly predictive of occult nodal metastasis. The 5-year OS, DSS, and RFS were 50.4%, 64.7%, and 63.4%, respectively. In conclusion, our single-institution data on a large cohort of patients, suggest performing routinely elective selective bilateral neck dissection during salvage total laryngectomy in cN0 patients due to the biological attitude of the tumor to spread to cervical nodes, considering an acceptable complications rate.

Factors Influencing Personalized Management of Vestibular Schwannoma: A Systematic Review.

Management of vestibular schwannoma (VS) is a complex process aimed at identifying a clinical indication for fractionated stereotactic radiotherapy (sRT) or microsurgical resection or wait and scan (WS). The aim of the review was to clarify which patient and tumor parameters may lead to different therapeutic choices, with a view to a personalized VS approach. A systematic review according to Preferred Reporting Items for Systematic Review and Meta-Analysis criteria was conducted between February and March 2022. The authors defined six parameters that seemed to influence decision-making in VS management: 1-incidental VS; 2-tumor size; 3-tumor regrowth after sRT; 4-subtotal resection; 5-patients' age; 6-symptoms. The initial search yielded 3532 articles, and finally, 812 articles were included. Through a qualitative synthesis of the included studies, management strategies were evaluated and discussed. An individualized proposal of procedures is preferable as compared to a single gold-standard approach in VS decision-making. The most significant factors that need to be considered when dealing with a VS diagnosis are age, tumor size and hearing preservation issues.

Clinical Markers of Need for Surgery in Orbital Complication of Acute Rhinosinusitis in Children: Overview and Systematic Review.

BACKGROUND: Although they can occur at all ages, orbital (OC) and periorbital cellulitis (POC) prevail in the pediatric population. Acute rhinosinusitis (ARS) is the most frequent predisposing factor of OC. Recent literature has suggested a medical management approach for OC and POC, with surgery reserved only for more severe cases. However, there is still a lack of consensus on the clinical markers of a need for surgery. The aim of this systematic review was to identify clinical markers of a need for surgery in children with OC. Our systematic review, in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) process, yielded 1289 articles finally screened. This resulted in 31 full texts that were included in a qualitative analysis. The results of this review suggest that in children aged over 9 years, large subperiosteal orbital abscesses (SPOAs), impaired vision, ophthalmoplegia, proptosis, elevated C-reactive protein (CRP) and absolute neutrophil counts (ANC), hemodynamic compromise, no clinical improvement after 48/72 h of antibiotic therapy, and a Chandler III score or higher are clinical markers of the need for surgery. However, most of the studies are observational and retrospective, and further studies are needed to identify reliable and repeatable clinical markers of the need for surgery.

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

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

Optimizing Pulmonary Outcomes After Total Laryngectomy: Crossover Study on New Heat and Moisture Exchangers.

OBJECTIVE: To evaluate the effects of new devices-heat and moisture exchangers (HMEs) and adhesives-on pulmonary symptoms, subject adherence, quality of life, dermatologic symptoms, and patient satisfaction after laryngectomy. STUDY DESIGN: Prospective crossover study. SETTING: Between December 2020 and April 2021, 40 patients were enrolled who had undergone laryngectomy, routinely used HMEs and adhesive, and were followed in our Department of Otolaryngology-Head and Neck Surgery. METHODS: Patients were allocated into group A (new products) or group B (usual care) for 6 weeks. Then the 2 groups reversed, and each patient acted as his or her own control. Patients kept a diary and cough tally sheet. At baseline and after each 6-week period, 2 questionnaires were administered: EQ-5D (European Quality of Life-5 Dimensions) and CASA-Q (Cough and Sputum Assessment Questionnaire). RESULTS: Six weeks of using new products resulted in the following effects for both groups: (1) a significant reduction in daily forced expectoration and dry coughs, (2) a significant improvement in all domains of the CASA-Q, (3) an increase in adherence to HME use, (4) a significant reduction in shortness of breath and skin irritation, and (5) significantly better scores in the anxiety/depression domain of the EQ-5D. CONCLUSION: Achieving this reduction in patients who were already highly adherent to HME use is clinically relevant and underscores the importance of using better-performing HMEs that can compensate for the humidification deficit. Improving pulmonary symptomatology could reduce patient restrictions in daily life and avoidance of social activity, with a consequent positive effect on quality of life.

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

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

A predictive nomogram for trismus after radiotherapy for head and neck cancer.

BACKGROUND: The aim of this study is to develop a prediction model for trismus (maximal interincisal distance equal to or less than 35 mm) based on a multivariable analysis of dosimetric and clinical factors. METHODS: The maximum inter-incisal opening (MIO) of hean and neck cancer (HNC) patients who underwent radiotherapy (RT) ± concurrent chemotherapy with radical intent, was prospectively measured prior to RT (baseline) and 6 months post-RT. The outcome variable is trismus. The potential risk factors (clinical and dosimetric) were first screened by univariate analysis and then by multivariate analysis. At the end of this process, we used the features identified as relevant, to fit a logistic regression model and calculate the probability of observed trismus during the 6-month follow-up after RT. RESULTS: One hundred and four consecutive patients were included (mean age 63 years, range 25-87), 68 males, 36 females. In the univariate analysis, the MIO at baseline, as an independent variable, and several Vdoses of different masticatory structures were found as significant. Additionally, using a bivariate model, a feature selection process was performed. Finally, we considered as best performing model the MIO at baseline and V42 at masseter muscles. The area under curve (AUC) of Receiver Operating Characteristic (ROC) curve value was 0.8255 (95% CI 0.74-0.9). The Hosmer and Lemeshow goodness-of-fit test, used to calibrate our model, was not-significant. CONCLUSIONS: A prediction nomogram was developed to assess trismus risk in planning process. An external validation of the model is required to apply it for current clinical use.

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

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