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.

Multicentre study on resection margins in carcinoma of the oral cavity, oro-hypopharynx and larynx.

Objective: The prognostic significance of the resection margins is still subject of conflicting opinions. The purpose of this paper is to report the results of a study on the margins in carcinoma of the oral cavity, oro-hypopharynx and larynx. Methods: A multicentre prospective study was carried out between 2015 and 2018 with the participation of 10 Italian reference hospitals. The primary objective was to evaluate local control in patients with well-defined clinical characteristics and comprehensive histopathological information. Results: During the study period, 455 patients were enrolled; the minimum follow-up was 2 years. Previous treatment, grading and fresh specimen examination were identified as risk factors for local control in multivariate analysis. On the basis of these results, it seems possible to delineate "risk profiles" for different oncological outcomes. Discussion: The prognostic significance of the margins is reduced, and other risk factors emerge, which require diversified treatment and follow-up. Conclusions: Multidisciplinary treatment with adjuvant therapy, if indicated, reduces the prognostic importance of margins. Collaboration with a pathologist is an additional favourable prognostic factor and quality indicator.An appendix with literature review is present in the online version.

Partially oxidized polyvinyl alcohol conduitfor peripheral nerve regeneration.

Surgical reconstruction of peripheral nerves injuries with wide substance-loss is still a challenge. Many studies focused on the development of artificial nerve conduits made of synthetic or biological materials but the ideal device has not yet been identified. Here, we manufactured a conduit for peripheral nerve regeneration using a novel biodegradable hydrogel we patented that is oxidized polyvinyl alcohol (OxPVA). Thus, its characteristics were compared with neat polyvinyl alcohol (PVA) and silk-fibroin (SF) conduits, through in vitro and in vivo analysis. Unlike SF, OxPVA and neat PVA scaffolds did not support SH-SY5Y adhesion and proliferation in vitro. After implantation in rat model of sciatic nerve transection, the three conduits sustained the regeneration of the injured nerve filling a gap of 5 mm in 12 weeks. Implanted animals showed a good gait recovery. Morphometric data related to the central portion of the explanted conduit interestingly highlighted a significantly better outcome for OxPVA scaffolds compared to PVA conduits in terms of axon density, also with respect to the autograft group. This study suggests the potential of our novel biomaterial for the development of conduits for clinical use in case of peripheral nerve lesions with substance loss.

Nm23-H1 nuclear expression is associated with a more favourable prognosis in laryngeal carcinoma: univariate and multivariate analysis.

AIMS: To use image analysis and multivariate analysis to investigate the prognostic significance of Nm23-H1 subcellular localization in a large cohort of laryngeal squamous cell carcinomas (LSCCs). METHODS AND RESULTS: Nm23-H1 total and nuclear levels were immunohistochemically determined and calculated with an image analysis system in 104 consecutively operated LSCCs. The mean follow-up was 58.3 ± 35.1 months (median 45 months). Total Nm23-H1 levels correlated only with patient stratification by pT (P=0.01). Mean nuclear Nm23-H1 levels were lower in patients with recurrent disease (P=0.01), and disease-free survival (DFS) was longer in patients whose nuclear levels of Nm23-H1 were >2.0% than in those with levels ≤ 2.0% (P=0.019). On multivariate analysis, Nm23-H1 nuclear expression [hazard ratio (HR) 2.59, P=0.005] and N stage (HR 3.60, P=0.0001) were prognostically significant in relation to DFS. CONCLUSIONS: In LSCC, Nm23-H1 nuclear expression may be useful for identifying patients at higher risk of recurrence after treatment and who might be considered for more aggressive therapy. Further investigations are needed before Nm23-H1 can be considered for use in targeted treatments for LSCC.

mTOR expression and prognosis in elderly patients with laryngeal carcinoma: uni- and multivariate analyses.

Cancer is common in the elderly, who may also be frail, which can complicate the choice of the best therapeutic approach. We sought to examine whether the serine-threonine kinase mTOR, a "master switch" in cancer cells that modulates metabolism, the cell cycle, and apoptosis, might help in clinical decision-making. The aim of the present study was thus to assess the potential prognostic role of mTOR in elderly patients with laryngeal carcinoma (LSCC). mTOR expression was determined immunohistochemically in 54 consecutive elderly (≥65 years old) patients with LSCC. On univariate analysis, nodal involvement and pathological stage correlated strongly with the elderly LSCC patients' prognosis in terms of disease recurrence rate and disease-free survival (DFS). Patients whose mTOR expression was >35.3% had a significantly higher recurrence rate (p=0.003) and shorter DFS (p=0.013). In the multivariate model, N status (p=0.001) and mTOR expression (p=0.026) maintained an independent prognostic significance in relation to DFS. mTOR probably influences the aggressive LSCC phenotype in elderly patients and its expression in elderly LSCC cases can be considered a prognostic marker potentially useful for identifying patients at higher risk of disease recurrence, and N0 patients at higher risk of recurrence who may benefit from more aggressive treatment. Since rapalogs (as mTOR inhibitors) might have an effect on LSCC, further investigations are needed to ascertain these agents' role in therapeutic strategies for advanced LSCC in elderly patients.

A scanning electron microscopic study of crimping of stapedial prostheses.

OBJECTIVE: The aim of this study was to evaluate, through the Scanning Electron Microscopy, the loop closure of four types of stapedial prostheses and to compare the different systems of crimping to the long process of the incus. MATERIALS AND METHODS: Four types of stapedial prostheses (one platinum-teflon, two different titanium and one nitinol-teflon pistons) were inserted in 40 specially prepared temporal bones simulating the in vivo stapedotomy procedure. Two pistons were crimped by single manual manoeuvre with a McGee microforceps; the remainders were self-retained and thermal-crimped, respectively. All the specimens were evaluated through the Operative Microscopy and the Scanning Electron Microscopy. RESULTS: Through the Operative Microscopy, all prostheses apparently achieved a correct adhesion to the long process of the incus; on the contrary the Scanning Electron Microscopy study demonstrated some limits of the manual crimping and the different coupling with the ossicular chain of each type of stapedial prosthesis. CONCLUSION: A complete adhesion of the prosthetic loop cannot be obtained because of the irregular profile of the incus at the site of attachment of the stapedial prosthesis. Consequently, on the basis of the morphological analysis with Scanning Electron Microscopy, in the surgical practice, the preference could be given to the stapedial prostheses that achieve greater contact such as the self-retaining and thermal crimping pistons compared to the standard sized prostheses considered.