The Impact of Dupilumab on Work Productivity and Emotional Health in CRSwNP: A Multicentric Study in Northeast Italy.

Chronic rhinosinusitis with nasal polyps (CRSwNP) in the severe forms is associated with a poor quality of life. Dupilumab has been suggested as an add-on treatment option for severe CRSwNP. Severe CRSwNP patients treated with Dupilumab in different rhinological units were considered for this study via their evaluation at the baseline at first and the consequential follow-up at 6-, 12-, and 24 months from the first administration. At baseline (T0) and at each follow-up, patients underwent NPS, Sinonasal Outcome Test (SNOT)-22, Visual Analogue Scale (VAS) for smell, and Sniffin' sticks identification test (SSIT). The SNOT-22 domains for function and emotion were also analysed separately. Two hundred and seventeen patients with at least 6 months of follow-up were included. All parameters have improved during treatment (p < 0.0001). Noticeably, both the function and emotion SNOT-22 domains have improved within 6 months of treatment and have continued to progress during every interval within 12 months from the baseline, positively influencing patients' emotivity and augmenting their social and economic performances. Dupilumab improves the QoL of CRSwNP patients with good effects on the reported productivity and emotional health. Clinicians should pay attention to these two aspects when dealing with patients affected by severe CRSwNP.

Polyps' Extension and Recurrence in Different Endotypes of Chronic Rhinosinusitis: A Series of 449 Consecutive Patients.

Different inflammatory endotypes reflect the heterogeneity of chronic rhinosinusitis with nasal polyps' (CRSwNPs) clinical presentation. This retrospective study aimed to analyze the distribution of polyps in nasal cavities and paranasal sinuses to establish a possible association between CRSwNP endotypes, prognosis, and polyps' extension. This study included 449 adult patients who underwent endoscopic sinus surgery for CRSwNPs between 2009 and 2022. Patients were categorized based on the number of paranasal sinuses involved by polyps. Statistical analyses, including Cox regression, were performed to identify associations between demographic, clinical, and histopathological factors and disease recurrence. CRSwNP patients were stratified into four groups based on the extent of polyp involvement. Asthma and acetylsalicylic acid (ASA) sensitivity were associated with more sinuses involved (p-values = 0.0003 and 0.0037, respectively). Blood eosinophil counts increased with the number of sinuses affected (p-value < 0.0001). The distribution of eosinophilic and non-eosinophilic histotypes varied significantly among these groups (p-value < 0.0001). The risk of CRSwNP recurrence was higher in patients with asthma, higher basophil percentages, and eosinophilic histotype (p-value 0.0104, 0.0001, 0.0118, and 0.0104, respectively). This study suggests a positive association between the number of paranasal sinuses involved by polyps and the severity of CRSwNPs, particularly in patients with eosinophilic histotype, asthma, and ASA sensitivity.

Blood Basophils Relevance in Chronic Rhinosinusitis with Aspirin-Exacerbated Respiratory Disease.

Aspirin-exacerbated respiratory disease (AERD) is characterized by eosinophilic asthma, chronic rhinosinusitis with nasal polyps (CRSwNP) and intolerance to cyclooxygenase-1 inhibitors. Interest is emerging in studying the role of circulating inflammatory cells in CRSwNP pathogenesis and its course, as well as their potential use for a patient-tailored approach. By releasing IL-4, basophils play a crucial role in activating the Th2-mediated response. The main aim of this study was to, first, investigate the level of the pre-operative blood basophils' values, blood basophil/lymphocyte ratio (bBLR) and blood eosinophil-to-basophil ratio (bEBR) as predictors of recurrent polyps after endoscopic sinus surgery (ESS) in AERD patients. The secondary aim was to compare the blood basophil-related variables of the AERD series (study group) with those of a control group of 95 consecutive cases of histologically non-eosinophilic CRSwNP. The AERD group showed a higher recurrence rate than the control group (p < 0.0001). The pre-operative blood basophil count and pre-operative bEBR were higher in AERD patients than in the control group (p = 0.0364 and p = 0.0006, respectively). The results of this study support the hypothesis that polyps removal may contribute to reducing the inflammation and activation of basophils.

The Prognostic Role of the Immune Microenvironment in Sinonasal Intestinal-Type Adenocarcinoma: A Computer-Assisted Image Analysis of CD3+ and CD8+ Tumor-Infiltrating Lymphocytes.

The prognostic value of conventional histopathological parameters in the sinonasal intestinal-type adenocarcinoma (ITAC) has been debated and novel variables should be investigated. Increasing evidence demonstrated that the evolution of cancer is strongly dependent upon the complex interactions within tumor microenvironment. The aim of this retrospective study was to assess the features of immune microenvironment in terms of CD3+ and CD8+ cells in a series of ITAC and explore their prognostic role, as well as their relations with clinicopathological variables. A computer-assisted image analysis of CD3+ and CD8+ tumor-infiltrating lymphocytes (TIL) density was conducted on surgical specimens of 51 patients with ITAC that underwent a curative treatment including surgery. ITAC displays variable TIL density, which is associated with OS. In a univariate model, the density of CD3+ TIL was significantly related to OS (p = 0.012), whereas the association with CD8+ TIL density resulted in being non-significant (p = 0.056). Patients with intermediate CD3+ TIL density were associated with the best outcome, whereas 5-year OS was the lowest for intermediate CD8+ TIL density. CD3+ TIL density maintained a significant association with OS in the multivariable analysis. TIL density was not significantly related to demographic and clinicopathological variables. CD3+ TIL density was independently associated with OS in a non-linear fashion and patients with intermediate CD3+ TIL density had the best outcome. Though based on a preliminary analysis on a relatively small series of patients, this finding makes TIL density a potential independent prognostic factor of ITAC.

Transnasal Endoscopic Approach for Osteoid Osteoma of the Odontoid Process in a Child: Technical Note and Systematic Review of the Literature.

Osteoid osteoma (OO) is a primary benign tumor that accounts for up to 3% of all bone tumors. The cervical spine is less affected by OOs, and very few cases of C2 OOs have been reported in the literature, both in adults and children. Surgery may be required in case of functional torticollis, stiffness, and reduced range of motion (ROM) due to cervical OOs refractory to medical therapy. Several posterior and anterior surgical techniques have been described to remove C2 OOs. In particular, anterior approaches to the cervical spine represent the most used surgical route for treating C2 OOs. We describe the first case of OO of the odontoid process removed through a transnasal endoscopic approach with the aid of neuronavigation in a 6-year-old child. No intraoperative complications occurred, and the post-operative course was uneventful. The patient had immediate relief of neck pain and remained pain-free throughout the follow-up period, with complete functional recovery of the neck range of motion (ROM). In this case, based on the favorable anatomy, the transnasal endoscopic approach represented a valuable strategy for the complete removal of an anterior C2 OO without the need for further vertebral fixation since the preservation of ligaments and paravertebral soft tissue.

Primary temporal bone squamous cell carcinoma: Comparing the prognostic value of the American Joint Committee on Cancer TNM classification (8th edition) with the revised Pittsburgh staging system.

BACKGROUND: Retrospectively considering a temporal bone squamous cell carcinomas (TBSCCs) series, our aim was to compare the predictive power of the American Joint Committee on Cancer (AJCC) staging system (8th edition) with the revised Pittsburgh staging system (rPSS) in terms of disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS). METHODS: Forty-three TBSCCs consecutively treated surgically were reviewed. The prognostic performance of AJCC and rPSS was compared. RESULTS: The areas under the curves for the prediction of DFS, DSS, and OS did not differ significantly between both staging systems (p = 0.518, p = 0.940, and p = 0.910, respectively). Harrel's C-indexes for respectively the AJCC and rPSS were 0.76 and 0.70 for DFS, 0.73 and 0.76 for DSS, 0.66 and 0.63 for OS. CONCLUSION: Comparable prognostic accuracy was observed between AJCC and rPSS. Levels of prognostic performance were only acceptable for both systems, according to Hosmer-Lemeshow scale. Further efforts are needed to define new TBSCC staging modalities with higher prognostic reliability.

Angiogenesis, programmed death ligand 1 (PD-L1) and immune microenvironment association in laryngeal carcinoma.

In the specific field of laryngeal carcinoma (LSCC), evidence about the interaction between angiogenetic pathway and immune microenvironment has not yet been explored. Given the potential relevance of such an interaction for prognostic and therapeutic purposes, the main aim of this exploratory study was to investigate the existence of a correlation between angiogenesis (quantified through CD31 expression), programmed cell death ligand 1 (PD-L1) expression, and immune microenvironment. A secondary aim was to verify whether considering a combination of angiogenesis and immune microenvironment variables might improve prognostic accuracy compared to the traditional clinical-pathological prognostic tools. CD31-assessed micro-vessel density (MVD), PD-L1 in terms of combined positive score (CPS), and tumour infiltrating lymphocytes (TILs) were assessed on 45 consecutive cases of LSCC. Cox proportional hazards model revealed increasing CD31-assessed MVD values, PD-L1 CPS <1, and TILs count rate <30%, as predictive of reduced disease free survival (DFS). Multivariate analysis found that MVD (p<0.0001) and TILs (p=0.0420) retained their significant independent prognostic value. Spearman's correlation model disclosed a significant negative correlation between CD31-assessed MVD values and PD-L1 CPS (p=0.0040). PD-L1 CPS and TILs count rate were positively correlated (p<0.0001). DFS was significantly lower in the CD31-assessed MVD >7, PD-L1 CPS <1, TILs <30% group than in the MVD ≤7, PD-L1 CPS ≥1, TILs ≥30% group (p=0.0001). These data preliminarily support an integrated interpretation of the prognostic role or angiogenesis and immune microenvironment markers in LSCC. This is of potential clinical relevance suggesting a synergistic effect of the combination of anti-angiogenic drugs with programmed death-1/PD-L1 checkpoint inhibitors in advanced LSCC.

COVID-19 in the tonsillectomised population.

OBJECTIVE: Interactions between SARS-CoV-2 and pharyngeal associated lymphoid tissue are thought to influence the manifestations of COVID-19. We aimed to determine whether a previous history of tonsillectomy, as a surrogate indicator of a dysfunctional pharyngeal associated lymphoid tissue, could predict the presentation and course of COVID-19. METHODS: Multicentric cross-sectional observational study involving seven hospitals in Northern and Central Italy. Data on the clinical course and signs and symptoms of the infection were collected from 779 adults who tested positive for SARS-CoV-2, and analysed in relation to previous tonsillectomy, together with demographic and anamnestic data. RESULTS: Patients with previous tonsillectomy showed a greater risk of fever, temperature higher than 39°C, chills and malaise. No significant differences in hospital admissions were found. CONCLUSIONS: A previous history of tonsillectomy, as a surrogate indicator of immunological dysfunction of the pharyngeal associated lymphoid tissue, could predict a more intense systemic manifestation of COVID-19. These results could provide a simple clinical marker to discriminate suspected carriers and to delineate more precise prognostic models.

Six-Month Psychophysical Evaluation of Olfactory Dysfunction in Patients with COVID-19.

This study prospectively assessed the 6-month prevalence of self-reported and psychophysically measured olfactory dysfunction in subjects with mild-to-moderate COVID-19. Self-reported smell or taste impairment was prospectively evaluated by SNOT-22 at diagnosis, 4-week, 8-week, and 6-month. At 6 months from the diagnosis, psychophysical evaluation of olfactory function was also performed using the 34-item culturally adapted University of Pennsylvania Smell Identification Test (CA-UPSIT). 145 completed both the 6-month subjective and psychophysical olfactory evaluation. According to CA-UPSIT, 87 subjects (60.0%) exhibited some smell dysfunction, with 10 patients being anosmic (6.9%) and seven being severely microsmic (4.8%). At the time CA-UPSIT was administered, a weak correlation was observed between the self-reported alteration of the sense of smell or taste and olfactory test scores (Spearman's r = -0.26). Among 112 patients who self-reported normal sense of smell at last follow-up, CA-UPSIT revealed normal smell in 46 (41.1%), mild microsmia in 46 (41.1%), moderate microsmia in 11 (9.8%), severe microsmia in 3 (2.3%), and anosmia in 6 (5.4%) patients; however, of those patients self-reporting normal smell but who were found to have hypofunction on testing, 62 out of 66 had a self-reported reduction in sense of smell or taste at an earlier time point. Despite most patients report a subjectively normal sense of smell, we observed a high percentage of persistent smell dysfunction at 6 months from the diagnosis of syndrome coronavirus 2 (SARS-CoV-2) infection, with 11.7% of patients being anosmic or severely microsmic. These data highlight a significant long-term rate of smell alteration in patients with previous SARS-COV-2 infection.

Temporal bone carcinoma: testing the prognostic value of a novel clinical and histological scoring system.

PURPOSE: Our group recently proposed the novel Padova prognostic scoring system for temporal bone carcinoma (TBSCC) that considers: the revised Pittsburgh staging system; radiological dura mater involvement; non-anterior spread (medial, inferior or posterior into the temporal bone and skull base) of T4 tumors; and histological grade. The aim of the present study was to validate this prognostic TBSCC scoring system in a case series selected from the literature. METHODS: A search was run to identify studies on TBSCC reporting the variables included in our score for each patient. Then our system was applied to the data extracted. RESULTS: Only two published investigations reported all the clinical and pathological data required for our scoring system. In one series from the Gruppo Otologico in Piacenza (Italy), a significantly higher recurrence rate (p = 0.008), shorter disease-free survival (DFS) (p = 0.001), higher disease-specific mortality (DSM) (p = 0.006), and shorter disease-specific survival (DSS) (p = 0.004) were associated with scores ≥ 5. Receiver operating curve (ROC) analysis showed an AUC of 0.804 for TBSCC recurrence, and 0.832 for DSM. In a series from Kyushu University Hospital (Japan), a significantly higher DSM (p = 0.018) and shorter DSS (p = 0.021) were associated with scores ≥ 5. ROC analysis showed an AUC of 0.812 for tumor relapse and 0.790 for DSM. CONCLUSION: Our TBSCC Padova scoring system confirmed its validity when applied to the only two international TBSCC series providing the required data. These preliminary results need to be confirmed in a multi-center prospective setting.

Transmeatal microsurgery for intralabyrinthine and intrameatal schwannomas: a reappraisal.

OBJECTIVE: The interest in surgical routes to the internal auditory canal (IAC) through the external auditory canal for vestibular schwannoma removal has been recently raised by the endoscopic approaches to the lateral skull base. The aim of the study was to reappraise the transmeatal microsurgical approach (TMMa) to the labyrinth and IAC, first described 50 years ago. METHODS: A retrospective series of 8 consecutive patients treated for intralabyrinthine and intrameatal schwannomas through TMMa is presented. Main outcome measures consisted of surgical indications, postoperative complications, facial nerve status, bed mobilisation time, hospitalisation time and tumour recurrence rate. RESULTS: Surgical indications for TMMa were tumour growth (62.5%) and disabling vertigo (37.5%) in the present series. Complete tumour removal with no complications and postoperative normal facial nerve function was obtained in all cases. Bed mobilisation occurred after a median of 3 postoperative days (IQR 2.2-3.0) and discharge after a median of 5.6 days (IQR 4.7-7.0). After a median follow-up of 13 months (IQR 7.5-27.5), no tumour recurrence was observed. CONCLUSIONS: TMMa indications are limited to schwannomas of the labyrinth and IAC, which dropped out from observation protocols due to unmanageable symptoms or growth. Despite the narrow mini-invasive surgical corridor, the TMMa was a safe an effective microsurgical technique in terms of tumour removal and postoperative course.

Temporal bone carcinoma: Novel prognostic score based on clinical and histological features.

BACKGROUND: This study aimed to develop a novel temporal bone squamous cell carcinoma (TBSCC) prognosis scoring system and compare it with the revised Pittsburgh staging system. METHODS: Forty-four consecutive TBSCC patients were assessed to identify predictors of recurrence. Each predictor's hazard ratio for recurrence was used to develop our novel scoring system. RESULTS: Based on variables with P < .10 in Cox's regression model, our score included: revised Pittsburgh stage; non-anterior spread of T4 carcinoma; dural involvement; and histological grade. A higher recurrence rate (P = .000) and shorter disease-free survival (P = .000) were associated with scores of ≥5. The area under the curve of our score was larger than that of the revised Pittsburgh stage for both recurrence and disease-specific mortality (P = .0178 and P = .0193, respectively). CONCLUSION: Our TBSCC scoring system is based on variables that are obtainable preoperatively from clinical and radiological data and biopsies. Its prognostic value should be validated for published TBSCC series and then in prospective settings.