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Titanium middle ear (ME) prostheses are widely used in surgical practice due to their acoustic properties. However, they present a significant drawback shared by all synthetic materials currently in use for ME reconstruction: they can be rejected by the organism of the host. In this study, we aim to review the current literature on titanium partial ossicular replacement prostheses (PORPs) and total ossicular replacement prostheses (TORPs) extrusion and dislocation. Eighty articles were analysed after a full article review based on the inclusion and exclusion criteria. The most common indication for reconstruction was chronic otitis media with cholesteatoma. The average extrusion or dislocation rate was 5.2%, ranging from 0 to 35%. The average improvements in the air-bone gap were 12.1 dB (1.6 dB to 25.1 dB) and 13.8 (-0.5 dB to 22.7 dB) for the PORP and TORP groups, respectively. The data reported on this topic are highly variable, demonstrating that functional outcomes are difficult to predict in clinical practice. We believe that the current limitations could be overcome with technological developments, including bioengineering research focused on promoting prosthesis adaptation to the ME environment.

Background: To make the regenerative process more effective and efficient, tissue engineering (TE) strategies have been implemented. Three-dimensional scaffolds (electrospun or 3D-printed), due to their suitable designed architecture, offer the proper location of the position of cells, as well as cell adhesion and the deposition of the extracellular matrix. Moreover, the possibility to guarantee a concomitant release of drugs can promote tissue regeneration., Methods: A PLA/PCL copolymer was used for the manufacturing of electrospun and hybrid scaffolds (composed of a 3D-printed support coated with electrospun fibers). Dexamethasone was loaded as an anti-inflammatory drug into the electrospun fibers, and the drug release kinetics and scaffold biological behavior were evaluated., Results: The encapsulation efficiency (EE%) was higher than 80%. DXM embedding into the electrospun fibers resulted in a slowed drug release rate, and a slower release was seen in the hybrid scaffolds. The fibers maintained their nanometric dimensions (less than 800 nm) even after deposition on the 3D-printed supports. Cell adhesion and proliferation was favored in the DXM-loading hybrid scaffolds., Conclusions: The hybrid scaffolds that were developed in this study can be optimized as a versatile platform for soft tissue regeneration.

Salivary gland cancers (SGCs) are rare, accounting for less than 5% of all malignancies of the head and neck region, and are morphologically heterogeneous. The diagnosis is mainly based on histology, with the complementary aid of molecular profiling, which is helpful in recognizing some poorly differentiated, borderline, or atypical lesions. Instrumental imaging defines the diagnosis, representing a remarkable tool in the treatment plan. Ultrasound and magnetic resonance are the most common procedures used to describe the primary tumour. The treatment of SGCs is multimodal and consists of surgery, radiotherapy, and systemic therapy; each treatment plan is, however, featured on the patient and disease's characteristics. On 24 June 2022, in the meeting "Current management and future challenges in salivary gland cancers" many experts in this field discussed the state of the art of SGCs research, the future challenges and developments. After the meeting, the same pool of experts maintained close contact to keep these data further updated in the conference proceedings presented here. This review collects the insights and suggestions that emerged from the discussion during and after the meeting per se., Competing Interests: LDL received conference honoraria/advisory board fees from: Lilly, MSD, EISAI, Roche, Bayer, Merck Serono, Istituto Gentili Srl, New Bridge; RF had consulting or Advisory Role in Regeneron, Sanofi, Prelude Therapeutics, Elevar Therapeutics, Guidepoint, Expert Connect, Remix, Eisai, Bioatla, Coherus in the past 24 months and received Research Funds Inst from Prelude, Ayala, Merck, Genentech, Pfizer, Rakuten, Nanobiotix, EMD Serono, ISA, Viracta, and Gilead in the past 24 months; LL received Research funds donated directly to the institution for clinical trials from: Adlai Nortye, Astrazeneca, BMS, Debiopharm International SA, Eisai, Eli Lilly and Company, Exelixis, Hoffmann-La Roche ltd, Isa Therapeutics, Kura Oncology, Merck-Serono, MSD, Merck Sharp&Dome Corp, Nektar Therapeutics, Novartis, Regeneron, Roche, Sanofi, Syneos, Sun Pharmaceutica and received occasional fees for participation as a speaker at conferences/congresses or as a scientific consultant for advisory boards from: Adlai Nortye, Astrazeneca, Bicara Therapeutics, DRG part of Clarivate, Genmab US, GlaxoSmithKline, Bayer, Mirati Therapeutics, MSD, Merck-Serono, Merck Healthcare KGaA, Neutron Therapeutics Inc, Seagen International BmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Locati, Ferrarotto, Licitra, Benazzo, Preda, Farina, Gatta, Lombardi, Nicolai, Vander Poorten, Chua, Vischioni, Sanguineti, Morbini, Fonseca, Sozzi, Merlotti and Orlandi.)

In this work, four different active encapsulation methods, microfluidic (MF), sonication (SC), freeze-thawing (FT), and electroporation (EP), were investigated to load a model protein (bovine serum albumin-BSA) into neutral liposomes made from 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC):cholesterol (Chol) and charged liposomes made from DSPC:Chol:Dioleoyl-3-trimethylammonium propane (DOTAP), DSPC:Chol:1,2-dioleoyl-sn-glycero-3-phospho-L-serine (DOPS), and DSPC:Chol:phosphatidylethanolamine (PE). The aim was to increase the protein encapsulation efficiency (EE%) by keeping the liposome size below 200 nm and the PDI value below 0.7, which warrants a nearly monodisperse preparation. Electroporation (100 V) yielded the best results in terms of EE%, with a dramatic increase in liposome size (>600 nm). The FT active-loading method, either applied to neutral or charged liposomes, allowed for obtaining suitable EE%, keeping the liposome size range below 200 nm with a suitable PDI index. Cationic liposomes (DSPC:Chol:DOTAP) loaded with the FT active method showed the best results in terms of EE% (7.2 ± 0.8%) and size (131.2 ± 11.4 nm, 0.140 PDI). In vitro release of BSA from AM neutral and charged liposomes resulted slower compared to PM liposomes and was affected by incubation temperature (37 °C, 4 °C). The empty charged liposomes tested for cell viability on Human Normal Dermal Fibroblast (HNDF) confirmed their cytocompatibility also at high concentrations (10 10 particles/mL) and cellular uptake at 4 °C and 37 °C. It can be concluded that even if both microfluidic passive and active methods are more easily transferable to an industrial scale, the FT active-loading method turned out to be the best in terms of BSA encapsulation efficiencies, keeping liposome size below 200 nm.

Objective: To assess artifact size and MRI visibility when applying the "Orthopedic-Metal Artifact Reduction" (O-MAR) algorithm for cochlear implant (CI) scanning., Methods: Two volunteers were submitted to 1.5 T MRI with an Ultra 3D CI receiver stimulator placed on their head. Four angular CI orientations were adopted: 90, 120, 135 and 160 degrees. Volunteers were scanned in each condition using T1w and T2w TSE sequences, as well as O-MAR sequences, in both axial and coronal planes. Quantitative comparisons were made of signal void and penumbra extent. Additionally, qualitative evaluations of global image quality, MRI readability with respect to 12 anatomical structures and visibility through the penumbra were undertaken., Results: After application of the O-MAR protocol, the radius of the signal void reduced from 50.76 mm to 45.43 mm and from 49.22 mm to 40.15 mm on T1w and T2w TSE axial sequences, respectively (p < 0.05). Qualitatively, sequences acquired with O-MAR produced better outcomes in terms of image quality and anatomical depiction. Despite the area of the penumbra being increased for the O-MAR protocol, visibility through penumbra was improved., Conclusions: Application of O-MAR may provide a complementary strategy to those already in use to obtain diagnostically useful MRI examinations in the presence of a CI, especially in case of skull base diseases requiring MRI monitoring., (Copyright © 2023 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

Background: Refractory or metastatic nasopharyngeal carcinoma (NPC) patients have a poor prognosis due to the lack of effective salvage treatments and prolonged survival by means of combination chemotherapy being described only for a minority of younger patients with oligometastatic disease. Targeting the Epstein - Barr virus (EBV) proteins expressed in NPC cells has been shown to be a feasible strategy that could help control systemic disease., Patients and Methods: Between 2011 and 2014, 16 patients with recurrent/metastatic EBV-NPC received first-line chemotherapy (CT) followed by 2 doses of autologous cytotoxic EBV specific T-lymphocytes (15-25 x 10 7 total cells/dose, 2 weeks apart), based on our previous studies showing the feasibility and efficacy of this infusion regimen. Cumulative overall survival (OS) and median OS were analysed in the whole population and according to specific clinical and biological parameters., Results: All patients received the planned T-cell therapy schedule, 9 after reaching partial (n=5) or complete (n=4) disease remission with CT, and 7 after failing to obtain benefit from chemotherapy. No severe adverse events were recorded. Patients who received cytotoxic T-lymphocytes (CTLs) had a cumulative 10-year OS of 44%, with a median OS of 60 months (95% CI 42-62). Patients responding to CT, with oligometastatic disease (<3 disease sites), and plasma EBV-DNA <1000 copies/mL had a better outcome., Conclusions: Autologous EBV-specific CTLs transplanted following conventional first-line CT demonstrated promising efficacy with several patients obtaining long-lasting disease control. The rationale provided by this study, with the crucial role likely played by the timing of CTL administration when trying to induce synergy with conventional treatment needs to be confirmed in a prospective controlled trial., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Secondino, Pedrazzoli, Basso, Bossi, Bianco, Imarisio, Pagani, De Cicco, Muscianisi, Casanova, Morosi, Bergamini, Benazzo, Cossu Rocca, Perotti, Baldanti, Zecca, Licitra and Comoli.)

Introduction: The problem of organs' shortage for transplantation is widely known: different manufacturing techniques such as Solvent casting, Electrospinning and 3D Printing were considered to produce bioartificial scaffolds for tissue engineering purposes and possible transplantation substitutes. The advantages of manufacturing techniques' combination to develop hybrid scaffolds with increased performing properties was also evaluated. Methods: Scaffolds were produced using poly-L-lactide-co-caprolactone (PLA-PCL) copolymer and characterized for their morphological, biological, and mechanical features. Results: Hybrid scaffolds showed the best properties in terms of viability (>100%) and cell adhesion. Furthermore, their mechanical properties were found to be comparable with the reference values for soft tissues (range 1-10 MPa). Discussion: The created hybrid scaffolds pave the way for the future development of more complex systems capable of supporting, from a morphological, mechanical, and biological standpoint, the physiological needs of the tissues/organs to be transplanted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pisani, Mauri, Negrello, Mauramati, Alaimo, Auricchio, Benazzo, Dorati, Genta, Conti, Ferretti, De Silvestri, Pietrabissa and Marconi.)

Objective: To report our experience in the use of silicone septal splint for recurrent severe epistaxis in hereditary haemorrhagic telangiectasia patients (HHT)., Methods: This is a descriptive analysis carried out at the Otorhinolaryngology Department of Fondazione IRCCS Policlinico San Matteo in Pavia, a reference centre for the treatment and diagnosis of HHT. We retrospectively evaluated HHT patients who underwent silicone septal splint positioning after the endoscopic surgical treatment of epistaxis from 2000 to 2022., Results: Of the 506 patients surgically treated in the period of analysis, 74 patients underwent silicone septal splint positioning and 37 were post-operatively interviewed. With a mean of 2.4 previous surgical treatments and a mean epistaxis severity of 7.38, the majority of patients presented with septal perforation (71.6%). On average, patients maintained the splint in place for 54.5 months, with a good tolerability and a significant reduction in epistaxis severity, need for blood transfusion and improvement of haemoglobin levels., Conclusions: In HHT patients with recurrent severe epistaxis and with septal perforation, the placement of septal splints offers a useful additional strategy in the management of nosebleeds., (Copyright © 2023 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

Objectives: Recurrent respiratory papillomatosis (RRP) is a benign, rare disease caused by Human Papilloma Virus (HPV) that can be divided into juvenile and adult forms. The course of the disease is variable, but is usually more aggressive in the juvenile form. The standard surgical treatment is represented by CO 2 laser resection, although photoangiolytic lasers represent a valid alternative. Adjuvant therapies have been proposed for disease control in case of frequent surgical resections or spreading into the lower airways. In recent years, the development of immunotherapy led to the use of bevacizumab either intratumorally or intravenously, but the most promising therapeutic development is represented by HPV vaccination. This paper aims to present a narrative review of the literature and the experience of three different University Centres in the treatment of RRP., Methods: A retrospective analysis of the clinical charts of all patients affected by laryngeal papillomatosis and treated in three different University Centres between 2002 and 2022 was performed. The following parameters were collected: sex, age at first evaluation, sites of larynx involved, HPV type, type of first surgical treatment, presence and number of recurrences, surgical treatment of recurrences, adjuvant therapies, side effects and status at last follow-up., Results: Seventy-eight patients were available for evaluation. Of these, 88% had adult onset RRP (Ao-RRP) and 12% juvenile onset RRP (Jo-RRP). The glottis was the most frequently involved subsite; all patients were submitted to surgical resection with CO 2 laser under general anaesthesia. Recurrences appeared in 79% of the patients, the patients who did not recur were all adults. The mean number of recurrences was 9 (range 1-110). Recurrences were more frequent in children (M = 20; range 2-110) than adults (M = 5; range 1-21). Thirty-two (52%) of the 62 patients who recurred were re-treated with CO 2 laser under general anaesthesia, while office-based treatment with a photoangiolytic laser was preferred in the remaining 30 (48%) patients. Adjuvant treatments were applied in 26 patients. The analysis of the course of the disease showed that in the 9 patients with Jo-RRP, 6 (67%) were free of lesions at the last follow-up, while the other 3 (33%) had papillomas. Of the 69 patients with Ao-RRP, 53 (77%) were alive and free of disease at the last visit, 14 (21%) were alive with disease, 1 (1%) was lost at follow-up and 1 (1%) died for other disease. Severe side effects were not observed except for 2 patients, who developed posterior glottic stenosis., Conclusions: Our results confirmed the literature review. RRP is a potentially aggressive disease, especially in juvenile onset. Surgical resection is still first-line treatment, but in case of multiple recurrences the use of adjuvant therapies must be taken into consideration., (Copyright © 2023 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

Background: Radiomics represents an emerging field of precision-medicine. Its application in head and neck is still at the beginning., Methods: Retrospective study about magnetic resonance imaging (MRI) based radiomics in oral tongue squamous cell carcinoma (OTSCC) surgically treated (2010-2019; 79 patients). All preoperative MRIs include different sequences (T1, T2, DWI, ADC). Tumor volume was manually segmented and exported to radiomic-software, to perform feature extraction. Statistically significant variables were included in multivariable analysis and related to survival endpoints. Predictive models were elaborated (clinical, radiomic, clinical-radiomic models) and compared using C-index., Results: In almost all clinical-radiomic models radiomic-score maintained statistical significance. In all cases C-index was higher in clinical-radiomic models than in clinical ones. ADC provided the best fit to the models (C-index 0.98, 0.86, 0.84 in loco-regional recurrence, cause-specific mortality, overall survival, respectively)., Conclusion: MRI-based radiomics in OTSCC represents a promising noninvasive method of precision medicine, improving prognosis prediction before surgery., (© 2023 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Objective: To establish the safety and effectiveness of subtotal petrosectomy with cochlear implantation in patients affected by chronic middle ear disorders to refractory to previous surgical treatments., Methods: A multicentre, retrospective study was conducted on patients affected by recalcitrant chronic middle ear disorders who underwent cochlear implantation in combination with subtotal petrosectomy. Patients' details were collected from databases of 11 Italian tertiary referral centres. Additionally, a review of the most updated literature was carried out., Results: 55 patients were included with a mean follow-up time of 44 months. Cholesteatoma was the most common middle ear recurrent pathology and 50.9% of patients had an open cavity. 80% of patients underwent a single stage surgery. One case of explantation for device failure was reported among the 7 patients with post-operative complications., Conclusions: Subtotal petrosectomy with cochlear implantation is a benchmark for management of patients with recalcitrant chronic middle ear disorders. A single stage procedure is the most recommended strategy. Optimal follow-up is still debated. Further studies are required to investigate the role of this surgery in paediatric patients., (Copyright © 2023 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

This study is a proof of concept performed to evaluate process parameters affecting shape memory effect of copolymer poly-L-lactide-co-poly-ε-caprolactone (PLA:PCL) 70:30 ratio based nanofibrous scaffolds. A design of experiment (DOE) statistical approach was used to define the interaction between independent material and process variables related to electrospun scaffold manufacturing, such as polymer solution concentration (w/v%), spinning time (min), and needle size (Gauge), and their influence on Rf% (ability of the scaffold to maintain the induced temporary shape) and Rr% (ability of the scaffold to recover its original shape) outputs. A mathematical model was obtained from DOE useful to predict scaffold Rf% and Rr% values. PLA-PCL 15% w/v, 22G needle, and 20-min spinning time were selected to confirm the data obtained from theoretical model. Subsequent morphological (SEM), chemical-physical (GPC and DSC), mechanical (uniaxial tensile tests), and biological (cell viability and adhesion) characterizations were performed., (© 2022. The Author(s).)

BACKGROUND Transoral robotic surgery (TORS) is an effective and safe option for obstructive sleep apnea syndrome (OSAS) patients with isolated retrolingual obstruction, as well as part of multilevel surgical approach in case of multilevel obstruction. Stenosis after TORS in OSAS patients is rarely described and no literature review has investigated this dramatic untoward event. CASE REPORT We report on a case of severe recalcitrant oropharyngeal stenosis after multilevel surgery with transoral robotic tongue base resection in an OSAS patient, leading to tracheotomy and gastrostomy dependence. Following the failure of numerous conservative therapeutic attempts, oropharyngeal patency was restored after extensive scar tissue removal through an open-neck approach, followed by a pharyngeal reconstruction with radial forearm free flap (RFFF). CONCLUSIONS Recalcitrant oropharyngeal stenosis is a dramatic complication that must be considered in OSAS patients submitted to TORS in a multilevel strategy and that is rarely described in the literature. A thorough review of the existing literature is presented to assess which factors are involved and the therapeutic strategies invoked in this scenario. The adoption of resection tools suited for robot-assisted surgery and the staging of TORS in case of multilevel surgery could decrease the risk of extensive scar formation. To date there is still no broad consensus on which therapeutic choice is the best for recalcitrant oropharyngeal stenosis. When minimally invasive treatments fail, a wide scar resection with a RFFF oropharyngeal reconstruction could be considered as a valuable option to restore the upper aerodigestive tract patency.

Squamous cell carcinoma is the most common malignancy that arises in the head-and-neck district. Traditional treatment could be insufficient in case of recurrent and/or metastatic cancers; for this reason, more selective and enhanced treatments are in evaluation in preclinical and clinical trials to increase in situ concentration of chemotherapy drugs promoting a selectively antineoplastic activity. Among all cancer treatment types (i.e., surgery, chemotherapy, radiotherapy), electroporation (EP) has emerged as a safe, less invasive, and effective approach for cancer treatment. Reversible EP, using an intensive electric stimulus (i.e., 1000 V/cm) applied for a short time (i.e., 100 μs), determines a localized electric field that temporarily permealizes the tumor cell membranes while maintaining high cell viability, promoting cytoplasm cell uptake of antineoplastic agents such as bleomycin and cisplatin (electrochemotherapy), calcium (Ca 2+ electroporation), siRNA and plasmid DNA (gene electroporation). The higher intracellular concentration of antineoplastic agents enhances the antineoplastic activity and promotes controlled tumor cell death (apoptosis). As secondary effects, localized EP (i) reduces the capillary blood flow in tumor tissue ("vascular lock"), lowering drug washout, and (ii) stimulates the immune system acting against cancer cells. After years of preclinical development, electrochemotherapy (ECT), in combination with bleomycin or cisplatin, is currently one of the most effective treatments used for cutaneous metastases and primary skin and mucosal cancers that are not amenable to surgery. To reach this clinical evidence, in vitro and in vivo models were preclinically developed for evaluating the efficacy and safety of ECT on different tumor cell lines and animal models to optimize dose and administration routes of drugs, duration, and intensity of the electric field. Improvements in reversible EP efficacy are under evaluation for HNSCC treatment, where the focus is on the development of a combination treatment between EP-enhanced nanotechnology and immunotherapy strategies.

Natural killer (NK) cells are emerging as unique players in the immune response against cancer; however, only limited data are available on tumor infiltrating NK cells in head and neck squamous cell carcinoma (HNSCC), one of the most common cancer. Occurrence of HNSCC is closely related to the immune microenvironment, and immunotherapy is increasingly being applied to this setting. However, the limited success of this type of treatment in this tumor calls for further investigation in the field. Surgical HNSSC specimens of 32 consecutive patients were mechanically and enzymatically dissociated. Tumor cells were separated from infiltrating cells by short centrifugation and infiltrating NK cells were phenotypically and functionally characterized by multiple antibody staining and flow cytometry. Tumor infiltrating NK cells in HNSCC showed a peculiar phenotype predominantly characterized by increased NKG2A and reduced Siglec-7, NKG2D, NKp30 and CD16 expression. This phenotype was associated with a decreased ability to perform antibody-dependent cellular cytotoxicity (ADCC). However, NK, CD4 and CD8 shared an increment of glucocorticoid-induced tumor necrosis factor-related (GITR) costimulatory receptor which could be exploited for immunotherapy with agonistic anti-GITR antibodies combined with checkpoint inhibitors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest, (Copyright © 2022 Mele, Pessino, Trisolini, Luchena, Benazzo, Morbini, Mantovani, Oliviero, Mondelli and Varchetta.)

Background: Smell and taste disturbances are among the most frequent neurological symptoms in patients with COVID-19. A concomitant impairment of the trigeminal nerve has been suggested in subjects with olfactory dysfunction, although it has not been confirmed with objective measurement techniques. In this study, we explored the trigeminal function and its correlations with clinical features in COVID-19 patients with impaired smell perception using electrophysiological testing., Methods: We enrolled 16 consecutive patients with mild COVID-19 and smell impairment and 14 healthy controls (HCs). Olfactory and gustatory symptoms were assessed with self-reported questionnaires. Electrophysiological evaluation of the masseter inhibitory reflex (MIR) and blink reflex (BR) was carried out to test the trigeminal function and its connections within the brainstem., Results: Masseter inhibitory reflex (MIR) analysis revealed higher latency of ipsilateral and contralateral early silent period in patients when compared with HCs. No significant differences between groups were detected as regards the duration of the early and late silent period. However, several patients showed a prolonged duration of the early silent period. BR evaluation disclosed only an increased amplitude of early components in patients., Conclusions: Patients with COVID-19 and smell impairment show a subclinical trigeminal nerve impairment. Trigeminal alterations mainly involve the oligosynaptic pathway, as a result of either direct viral damage or secondary neuroinflammation of the peripheral trigeminal fibers, whereas the polysynaptic ponto-medullary circuits seem to be spared. The prolonged duration of the early silent period and the increased amplitude of early BR response might reflect a compensatory upregulation of the trigeminal function as a consequence of the olfactory dysfunction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cosentino, Maiorano, Todisco, Prunetti, Antoniazzi, Tammam, Quartesan, Lettieri, De Icco, Corsico, Benazzo, Pisani, Tassorelli and Alfonsi.)

Alongside the currently used nasal swab testing, the COVID-19 pandemic situation would gain noticeable advantages from low-cost tests that are available at any-time, anywhere, at a large-scale, and with real time answers. A novel approach for COVID-19 assessment is adopted here, discriminating negative subjects versus positive or recovered subjects. The scope is to identify potential discriminating features, highlight mid and short-term effects of COVID on the voice and compare two custom algorithms. A pool of 310 subjects took part in the study; recordings were collected in a low-noise, controlled setting employing three different vocal tasks. Binary classifications followed, using two different custom algorithms. The first was based on the coupling of boosting and bagging, with an AdaBoost classifier using Random Forest learners. A feature selection process was employed for the training, identifying a subset of features acting as clinically relevant biomarkers. The other approach was centered on two custom CNN architectures applied to mel-Spectrograms, with a custom knowledge-based data augmentation. Performances, evaluated on an independent test set, were comparable: Adaboost and CNN differentiated COVID-19 positive from negative with accuracies of 100% and 95% respectively, and recovered from negative individuals with accuracies of 86.1% and 75% respectively. This study highlights the possibility to identify COVID-19 positive subjects, foreseeing a tool for on-site screening, while also considering recovered subjects and the effects of COVID-19 on the voice. The two proposed novel architectures allow for the identification of biomarkers and demonstrate the ongoing relevance of traditional ML versus deep learning in speech analysis., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Authors Giovanni Costantini, Giovanni Saggio, and Antonio Pisani are advisory members of VoiceWise S.r.l., spin-off company of University of Rome Tor Vergata (Rome, Italy) developing voice analysis solutions for diagnostic purposes; Valerio Cesarini cooperates with VoiceWise and is employed by CloudWise S.r.l., a company developing cloud data storage and software solutions., (© 2022 Elsevier B.V. All rights reserved.)

Objective: To perform a cross-cultural adaptation into Italian and to analyse reliability and validity of the Transsexual Voice Questionnaire for male-to-female transsexuals (I-TVQ MtF )., Study Design: Cross-sectional nonrandomized survey study., Methods: For item-generation, a cross-cultural adaptation and translation process was performed following standard guidelines. Transgender women were consecutively recruited and asked to fill out the I-TVQ MtF and a form on social, demographic and transition-related variables. Firstly, data collected from participants were used to perform confirmatory factor analysis, and to evaluate internal consistency and test-retest reliability Subsequently, convergent validity was evaluated comparing I-TVQ MtF total scores with the two extra items addressing self-perception (SPVF) and aspiration (AVF) of voice femininity. To evaluate convergent validity, scores of the Italian version of the Voice Handicap Index were considered for comparisons. A correlation analysis was performed to verify potential association between I-TVQ MtF scores and social, demographic and transition-related variables., Results: Confirmatory factor analysis demonstrated that a two-factor model fits data better than the unidimensional one. Both internal consistency and test retest reliability of the I-TVQ MtF were satisfactory. Negative correlations were highlighted between I-TVQ MtF scores on one side and self-perception vocal functioning and aspiration vocal functioning on the other. Positive correlations between I-TVQ MtF and Italian version of the Voice Handicap Index scores were also found. Finally, negative correlations were demonstrated between I-TVQ MtF scores and time spent living in the female role., Conclusion: The I-TVQ MtF appears to be a reliable and valid instrument for the assessment of voice-related quality of life in transgender women., (Copyright © 2020 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: To report the personalized decision-making pro- cess adopted for a cochlear implant (CI) candidate requiring magnetic resonance imaging (MRI) brain surveillance., Study Design: Clinical capsule report., Setting: Tertiary academic referral center., Patient: A 23-year-old man affected by posttraumatic bilat- eral profound hearing loss, already in radiological follow-up for a suspected small left cuneal low-grade glioma., Interventions: A multidisciplinary approach involving preoperative MRI simulations and 3D printed (3DP) models aiming to adapt the CI position to facilitate MRI brain lesion visibility., Main Outcome Measures: MRI visibility and surgical approach., Results: Preoperative MRI scans with the placement of an Ultra 3D CI were performed simulating different implant location to assess the brain lesion visibility in MRI. CI was positioned 9 cm away from the external auditory canal with an angle of 90 degrees. To assess the technical feasibility of the surgical procedure, a patient-specific 3DP head model was produced preoperatively. The postoperative course was uneventful, the patient showed a significant benefit from CI, and the brain lesion was highly visible at the MRI follow-up., Conclusions: The employment of strategies aimed at improving the MRI quality in CI recipients still represents a topic requiring attention. Thanks to multidisciplinary team collaboration, in our case, the CI position was successfully determined to allow unhindered MRI visibility of a specific intracranial structure., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2022, Otology & Neurotology, Inc.)

Purposes: To investigate the effects for Ultra 3D cochlear implant (CI) positioning on MR imaging quality, looking at a comprehensive description of intracranial structures in cases of unilateral and bilateral CI placement., Methods: Four CI angular positions (90°, 120°, 135° and 160°) at 9 cm distance from the outer-ear canal were explored. The 1.5 T MRI assessment included our institutional protocol for the investigation of brain pathologies without gadolinium application. Three investigators (two experienced neuroradiologists and one experienced otoneurosurgeon) independently evaluated the MR findings. A 4-point scale was adopted to describe 14 intracranial structures and to determine which CI positioning allowed the best image quality score and how bilateral CI placement modified MRI scan visibility., Results: A high positive correlation was found between the three blinded observers. Structures situated contralateral from the CI showed high-quality values in all four placements. Structures situated ipsilaterally provided results suitable for diagnostic purposes for at least one position. At 90°, artifacts mainly involved brain structures located cranially and anteriorly (e.g., temporal lobe); on the contrary, at 160°, artifacts mostly influenced the posterior fossa structures (e.g., occipital lobe). For the bilateral CI condition, MR imaging examination revealed additional artifacts involving all structures located close to either CI, where there was a signal void/distortion area., Conclusions: Suitable unilateral CI positioning can allow the visualization of intracranial structures with sufficient visibility for diagnostic purposes. Bilateral CI positioning significantly deteriorates the anatomical visibility. CI positioning might play a crucial role for patients who need post-operative MRI surveillance., (© 2021. The Author(s).)

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., (Copyright © 2022 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

Background: Parkinson's disease (PD) is a neurodegenerative disorder characterized by a combination of motor and non-motor dysfunction. Dysphagia is a common symptom in PD, though it is still too frequently underdiagnosed. Consensus is lacking on screening, diagnosis, and prognosis of dysphagia in PD., Objective: To systematically review the literature and to define consensus statements on the screening and the diagnosis of dysphagia in PD, as well as on the impact of dysphagia on the prognosis and quality of life (QoL) of PD patients., Methods: A multinational group of experts in the field of neurogenic dysphagia and/or PD conducted a systematic revision of the literature published since January 1990 to February 2021 and reported the results according to PRISMA guidelines. The output of the research was then analyzed and discussed in a consensus conference convened in Pavia, Italy, where the consensus statements were drafted. The final version of statements was subsequently achieved by e-mail consensus., Results: Eighty-five papers were used to inform the Panel's statements even though most of them were of Class IV quality. The statements tackled four main areas: (1) screening of dysphagia: timing and tools; (2) diagnosis of dysphagia: clinical and instrumental detection, severity assessment; (3) dysphagia and QoL: impact and assessment; (4) prognostic value of dysphagia; impact on the outcome and role of associated conditions., Conclusions: The statements elaborated by the Consensus Panel provide a framework to guide the neurologist in the timely detection and accurate diagnosis of dysphagia in PD., (© 2021. The Author(s).)

Shape-Memory Polymers (SMPs) are considered a kind of smart material able to modify size, shape, stiffness and strain in response to different external (heat, electric and magnetic field, water or light) stimuli including the physiologic ones such as pH, body temperature and ions concentration. The ability of SMPs is to memorize their original shape before triggered exposure and after deformation, in the absence of the stimulus, and to recover their original shape without any help. SMPs nanofibers (SMPNs) have been increasingly investigated for biomedical applications due to nanofiber's favorable properties such as high surface area per volume unit, high porosity, small diameter, low density, desirable fiber orientation and nanoarchitecture mimicking native Extra Cellular Matrix (ECM). This review focuses on the main properties of SMPs, their classification and shape-memory effects. Moreover, advantages in the use of SMPNs and different biomedical application fields are reported and discussed.

Acquired congenital esophageal malformations, such as malignant esophageal cancer, require esophagectomy resulting in full thickness resection, which cannot be left untreated. The proposed approach is a polymeric full-thickness scaffold engineered with mesenchymal stem cells (MSCs) to promote and speed up the regeneration process, ensuring adequate support and esophageal tissue reconstruction and avoiding the use of autologous conduits. Copolymers poly-L-lactide-co-poly-ε-caprolactone (PLA-PCL) 70:30 and 85:15 ratio were chosen to prepare electrospun tubular scaffolds. Electrospinning apparatus equipped with two different types of tubular mandrels: cylindrical (&empty; 10 mm) and asymmetrical (&empty; 10 mm and &empty; 8 mm) were used. Tubular scaffolds underwent morphological, mechanical (uniaxial tensile stress) and biological (MTT and Dapi staining) characterization. Asymmetric tubular geometry resulted in the best properties and was selected for in vivo surgical implantation. Anesthetized pigs underwent full thickness circumferential resection of the mid-lower thoracic esophagus, followed by implantation of the asymmetric scaffold. Preliminary in vivo results demonstrated that detached stitch suture achieved better results in terms of animal welfare and scaffold integration; thus, it is to be preferred to continuous suture.

Purpose: New-onset olfactory and gustatory dysfunction (OGD) represents a well-acknowledged COVID-19 red flag. Nevertheless, its clinical, virological and serological features are still a matter of debate., Materials and Methods: For this cohort study, 170 consecutive subjects with new-onset OGD were consecutively recruited. Otolaryngological examination, OGD subjective grading, nasopharyngeal swabs (NS) for SARS-CoV-2 RNA detection and serum samples (SS) collection for SARS-CoV-2 IgG quantification were conducted at baseline and after one (T1), two (T2) and four weeks (T3)., Results: SARS-CoV-2 infection was confirmed in 79% of patients. Specifically, 43% of positive patients were detected only by SS analysis. The OGD was the only clinical complaint in 10% of cases. Concurrent sinonasal symptoms were reported by 45% of patients. Subjective improvement at T3 was reported by 97% of patients, with 40% recovering completely. Hormonal disorders and RNA detectability in NS were the only variables associated with OGD severity. Recovery rate was higher in case of seasonal influenza vaccination, lower in patients with systemic involvement and severe OGD. Not RNA levels nor IgG titers were correlated with recovery., Conclusion: Clinical, virological and serological features of COVID-19 related OGD were monitored longitudinally, offering valuable hints for future research on the relationship between host characteristics and chemosensory dysfunctions., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Internal or common carotid artery encasement (CAE) is observed in almost 2-7% of head and neck cancers (HNC) and designates the tumor with the T4b category. This clinical scenario is associated with a dismal prognosis, owing to the risk for thrombosis and bleeding that usually characterizes such an advanced cancer. Standardized radiological criteria to infer invasion of the carotid artery are lacking. Complete surgical resection in the context of a multimodality treatment is supposed to offer the greatest chances of cure. Surgery can either be carotid-sparing or include carotidectomy. Data on probability of cerebrovascular and non-cerebrovascular complications, risk of carotid blowout, poor oncologic outcomes, and less-than-certain efficacy of diagnostic and interventional preventive procedures against cerebral infarction make it difficult to define surgery as the recommended option among other therapeutic strategies. Non-surgical therapies based on radiation therapy possibly combined with chemotherapy are more frequently employed in HNC with CAE. In this context, carotid blowout is the most feared complication, and its probability increases with tumor stage and cumulative radiation dose received by the vessel. The use of highly conformal radiotherapies such as intensity-modulated particle therapy might substantially improve the manageability of HNC with CAE by possibly reducing the risk of late sequalae. Despite evidence is frail, it appears logical that a case-by-case evaluation through multidisciplinary decision making between head and neck surgeons, radiation oncologists, medical oncologists, diagnostic and interventional radiologists, and vascular surgeons are of paramount value to offer the best therapeutic solution to patients affected by HNC with CAE., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Orlandi, Ferrari, Lafe, Preda, Benazzo, Vischioni, Bonora, Rampinelli, Schreiber, Licitra and Nicolai.)

Background: Dysphagia is common in Parkinson's disease (PD). The effects of antiparkinsonian drugs on dysphagia are controversial. Several treatments for dysphagia are available but there is no consensus on their efficacy in PD., Objective: To conduct a systematic review of the literature and to define consensus statements on the treatment of dysphagia in PD and related nutritional management., Methods: A multinational group of experts in the field of neurogenic dysphagia and/or Parkinson's disease conducted a systematic evaluation of the literature and reported the results according to PRISMA guidelines. The evidence from the retrieved studies was analyzed and discussed in a consensus conference organized in Pavia, Italy, and the consensus statements were drafted. The final version of statements was subsequently achieved by e-mail consensus., Results: The literature review retrieved 64 papers on treatment and nutrition of patients with PD and dysphagia, mainly of Class IV quality. Based on the literature and expert opinion in cases where the evidence was limited or lacking, 26 statements were developed., Conclusions: The statements developed by the Consensus panel provide a guidance for a multi-disciplinary treatment of dysphagia in patients with PD, involving neurologists, otorhinolaryngologists, gastroenterologists, phoniatricians, speech-language pathologists, dieticians, and clinical nutritionists., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Olfactory and taste disorders (OTD) are commonly found as presenting symptoms of SARS-CoV-2 infection in patients with clinically mild COVID-19. Virus-specific T cells are thought to play an important role in the clearance of SARS-CoV-2; therefore the study of T cell specific immune responses in patients with mild symptoms may help to understand their possible role in protection from severe disease. We evaluated SARS-CoV-2-specific T cell responses to four different peptide megapools covering all SARS-CoV-2 proteins during the acute phase of the disease in 33 individuals with mild or no other symptom beside OTD and in 22 age-matched patients with severe infection. A control group of 15 outpatients with OTD and consistently negative nasopharyngeal SARS-CoV-2 RNA swabs and virus-specific IgG serology was included in the study. Increased frequencies of virus-specific CD4 + and CD8 + T cells were found in SARS-CoV-2 positive patients with OTD compared with those with severe COVID-19 and with SARS-CoV-2 negative OTD individuals. Moreover, enhanced CD4 + and CD8 + T-cell activation induced by SARS-CoV-2 peptides was associated with higher interferon (IFN)γ production. Increased frequencies of Spike (S1/S2)-specific CD4 + T cells showing enhanced IFNγ secretion and granzyme B content were associated with serum spike-specific IgG in the OTD group. In conclusion, patients with SARS-CoV-2 induced OTD develop highly functional virus-specific CD4 + and CD8 + T cells during the symptomatic phase of the disease, suggesting that robust and coordinated T-cell responses provide protection against extension of COVID-19 to the lower respiratory tract., Competing Interests: AS is a consultant for Gritstone, Flow Pharma, Arcturus, Immunoscape, 20 CellCarta, OxfordImmunotech and Avalia. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mele, Calastri, Maiorano, Cerino, Sachs, Oliviero, Mantovani, Baldanti, Bruno, Benazzo, Grifoni, Sette, Mondelli and Varchetta.)

Objectives: To evaluate the role of nasal endoscopy for early clinical diagnosis of hereditary hemorrhagic telangiectasia (HHT) in children and to investigate the characteristics of epistaxis and mucocutaneous telangiectases in our pediatric population., Study Design: From May 2016 to December 2019, a cross-sectional observational study was conducted, recruiting children aged 2-18 years with a parent affected by HHT. To identify the Curaçao criteria, all children underwent collection of clinical history, mucocutaneous examination, and nasal endoscopy. The clinical data were then compared with the genetic data acquired subsequently., Results: Seventy children (median age, 10.8 years) were included. All underwent nasal endoscopy without complications. Forty-six children were positive by genetic testing; of these, 26 % had skin and oral telangiectases and 91 % had nasal telangiectases. The diagnostic sensitivity of the Curaçao criteria increased from 28 % (95 % CI, 16%-43 %) to 85 % (95 % CI, 71%-94 %; P < .0001) when the nasal telangiectases were included., Conclusions: The magnified and complete endoscopic view of the nasal cavities proved useful in increasing the diagnostic sensitivity of the Curaçao criteria. Such an examination turned out to be feasible and safe. For this reason, we believe that nasal endoscopy should be included in the diagnostic assessment of pediatric patients with suspected HHT., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purposes: To primarily evaluate MRI-induced effects for Ultra 3D cochlear implantation in human cadavers in terms of artifact generation and MR image quality., Methods: Three human cadaveric heads were submitted to imaging after unilateral and bilateral cochlear implantation. The 1.5 T MR examination protocol was chosen in accordance with our institutional protocol for the assessment of brain pathology. The maximal signal void size was measured according to each sequence and plane. Two experienced neuro-radiologists and one experienced otoneurosurgeon independently evaluated the MR image quality findings. A 4-point scale was used to describe the diagnostic usefulness of 14 brain structures., Results: Shape and size of the artifacts were found to be highly related to MRI sequences and acquisition planes. MRI sequences and processing algorithms affected the ability to assess anatomical visibility. Image quality appeared either high or assessable for diagnostic purposes in 9 out of 14 of the ipsilateral structures, in at least one plane. Anatomical structures contralateral to the cochlear implant were highly visible in all conditions. Artifact intrusion clearly improved after application of metal artifact-reduction techniques. In the case of bilateral cochlear implant, a mutual interaction between the two implant magnets produced an additional artifact., Conclusions: We performed the first cadaver study aimed at systematically evaluating the MRI-induced artifacts produced by a cochlear implant with a novel four bar magnet system. Specific brain structures can be assessable for diagnostic purposes under 1.5 T MRI, with the cochlear implant magnet in place., (© 2020. The Author(s).)

Introduction : Severe asthma and chronic rhinosinusitis (CRS), with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP), are heterogeneous diseases characterized by different mechanistic pathways (endotypes) and variable clinical presentations (phenotypes). Areas covered : This review provides the clinician with an overview of the prevalence and clinical impact of severe chronic upper and lower airways disease and suggests a novel therapeutic approach with biological agents with possible biomarkers. To select relevant literature for inclusion in this review, we conducted a literature search using the PubMed database, using terms 'severe airways disease' AND 'endotype' AND 'treatment.' The literature review was performed for publication years 2010-2020, restricting the articles to humans and English language publications. Expert opinion : The coronavirus disease (COVID-19) pandemic has brought forth many challenges for patients with severe airway disease and healthcare practitioners involved in care. These patients could have an increased risk of developing severe SARS-CoV-2 disease, although treatment with biologics is not associated with a worse prognosis. Eosinopenia on hospital admission plays a key role as a diagnostic and prognostic biomarker.

The clinical management of BRAF -mutated metastatic melanoma had an important turning point after the introduction of the targeted therapy. Despite the efficacy and good tolerability of this treatment, the development of resistance mechanisms causes disease progression. The aim of this review is to investigate the role of treatment beyond progression and locoregional approaches in BRAF -mutated metastatic melanoma and provide oncologists dealing with this malignancy a useful road map on when and why to choose this strategy. The article is structured in the form of a narrative review reporting the most significant studies on the subject. Most of the available articles are represented by retrospective studies and case reports, leading to limitations in the final interpretations. Nevertheless, a correct analysis of the selected studies allows the drawing of some conclusions. In well-selected cases, treatment beyond progression could play an important role in the treatment sequence of patients with BRAF -mutated advanced melanoma and would seem to produce good disease control rates and positive survival outcomes. A careful evaluation of the radiological examinations and laboratory tests, based on the clinical conditions, allows the identification of which patients can benefit from this strategy. Such patients are those who, at the time of progression, have favourable features such as a lower performance status according to Eastern Cooperative Oncology Group (ECOG-PS), normal lactate dehydrogenase levels and lower disease burden. The clinical benefit is also consolidated by the addition of locoregional approaches. Locoregional approaches can include electrochemotherapy, radiotherapy or surgery, and their use provides local disease control and a better quality of life for patients., Competing Interests: Disclosure and potential conflicts of interest: The authors declare that they have no conflicts of interest relevant to this manuscript. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2021/07/dic.2021-3-1-COI.pdf, (Copyright © 2021 Serra F, Faverio C, Lasagna A, Barruscotti S, Dominioni T, Benazzo M, Pedrazzoli P, Chiellino S.)

Purpose: The aim of this study is to evaluate the prognostic value of pre-treatment advanced lung cancer inflammation index (ALI) in patients with HPV-negative HNSCC undergoing up-front surgical treatment., Methods: The present multi-centre, retrospective study was performed in a consecutive cohort of patients who underwent upfront surgery with or without adjuvant (chemo)-radiotherapy for head and neck squamous cell carcinoma (HNSCC). Patients were stratified by ALI, and survival outcomes were compared between groups. In addition, the prognostic value of ALI was compared with two other indices, the prognostic nutritional index (PNI) and systemic inflammatory index (SIM)., Results: Two hundred twenty-three patients met the inclusion criteria (151 male and 72 female). Overall and progression-free survival were significantly predicted by ALI < 20.4 (HR 3.23, CI 1.51-6.90 for PFS and HR 3.41, CI 1.47-7.91 for OS). Similarly, PNI < 40.5 (HR = 2.43, 95% CI: 1.31-4.51 for PFS and HR = 2.40, 95% CI: 1.19-4.82 for OS) and SIM > 2.5 (HR = 2.51, 95% CI: 1.23-5.10 for PFS and HR = 2.60, 95% CI: 1.19-5.67 for OS) were found to be significant predictors. Among the three indices, ALI < 20.4 identified the patients with the worst 5-year outcomes. Moreover, patients with a combination of low PNI and low ALI resulted to be a better predictor of progression (HR = 5.26, 95% CI: 2.01-13.73) and death (HR = 5.68, 95% CI: 1.92-16.79) than low ALI and low PNI considered alone., Conclusions: Our results support the use of pre-treatment ALI, an easily measurable inflammatory/nutritional index, in daily clinical practice to improve prognostic stratification in surgically treated HPV-negative HNSCC.

Nearly 250 years ago, Antonio Scarpa became a professor of anatomy and surgery only 2 years after he graduated from the University of Padua. The young lecturer soon became one of the most renowned anatomists in Italy and a director of the Faculty of Medicine at the University of Pavia. He worked in the fields of general surgery and ophthalmology. Several anatomic structures have been named after him, mainly Scarpa fascia and Scarpa triangle. His interest in neuroanatomy was ardent, despite being occasionally neglected. Scarpa's contributions to the fields of neurosciences have been significant. He was the first to describe the round window and the secondary tympanic membrane, and he eventually focused on the auditory and olfactory organs. Notably, the vestibular ganglion is now known as Scarpa ganglion. Scarpa's magnum opus was the book Tabulae Neurologicae, in which he described the path of several cranial nerves including the vagus nerve and innervation of the heart. Since his death in 1832, Scarpa's head has been preserved at the University History Museum of the University of Pavia. In this historical vignette, we aim to describe Antonio Scarpa's troubled life and brilliant career, focusing on his core contributions to neuroanatomy, neurosurgery, and otoneurosurgery., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Over 50% of patients with head-and-neck squamous cell carcinoma (HNSCC) experience locoregional recurrence, which is associated with poor outcome. In the course of follow-up for patients surviving primary surgery for HNSCC, one might ask: What is the probability of recurrence in one year considering that the cancer has not yet recurred to date?, Materials and Methods: To answer this question, 979 patients surgically treated for HNSCC (i.e. cancer of the oral cavity, oropharynx, hypopharynx or larynx) between March 2004 and June 2018 were enrolled in a multicenter retrospective cohort study, followed up for death and recurrence over a 5 year period. The conditional probability of recurrence in 12 months - i.e. the probability of recurrence in the next 12 months given that, to date, the patient has not recurred - was derived from the cumulative incidence function (Aalen-Johansen method)., Results: Overall, the probability of recurrence was the highest during the first (17.3%) and the second years (9.6%) after surgery, declining thereafter to less than 5.0% a year thereafter. The probability of recurrence was significantly higher for stage III-IV HNSCCs than for stage I-II HNSCCs in the first year after surgery (20.4% versus 10.0%; p  < 0.01), but not thereafter. This difference was most pronounced for oral cavity cancers. No significant differences were observed across different tumor sites., Conclusion: This dynamic evaluation of recurrence risk in patients surgically treated for HNSCC provides helpful and clinically meaningful information, which can be useful to patients in planning their future life, and to clinicians in tailoring post-treatment surveillance according to a more personalized risk stratification.

Objectives: SARS-CoV-2 T-cell response characterization represents a crucial issue for defining the role of immune protection against COVID-19. The aim of the study was to assess the SARS-CoV-2 T-cell response in a cohort of COVID-19 convalescent patients and in a group of unexposed subjects., Methods: SARS-CoV-2 T-cell response was quantified from peripheral blood mononuclear cells (PBMCs) of 87 COVID-19 convalescent subjects (range 7-239 days after symptom onset) and 33 unexposed donors by ex vivo ELISpot assay. Follow-up of SARS-CoV-2 T-cell response was performed in ten subjects up to 12 months after symptom onset. The role of SARS-CoV-2 specific CD4 and CD8 T cells was characterized in a group of COVID-19 convalescent subjects. Moreover, neutralizing antibodies were determined in serum samples., Results: In 14/33 (42.4%) unexposed donors and 85/87 (97.7%) COVID-19 convalescent subjects a positive result for at least one SARS-CoV-2 antigen was observed. A positive response was observed up to 12 months after COVID-19 infection (median 246 days after symptom onset; range 118-362 days). Of note, SARS-CoV-2 T-cell response seems to be mainly mediated by CD4 T cells. A weak positive correlation was observed between Spike-specific T-cell response and neutralizing antibody titre (p 0.0028; r 2  = 0.2891) and positive SARS-CoV-2 T-cell response was observed in 8/9 (88.9%) COVID-19 convalescent subjects with undetectable SARS-CoV-2 neutralizing antibodies., Discussion: Cross-reactive SARS-CoV-2 T-cell response in uninfected patients may be due to previous infections with other common coronaviruses. Our data suggest that long-term SARS-CoV-2 T-cell response might accompany a waning humoral response., (Copyright © 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

A successful regenerative process has to consider the role of immune system after surgical implantation of a polymer-based matrix due to the reaction of monocytes and macrophages cells after contact with biomaterial. Pro-inflammatory (TNF-alfa, IL-6 and IL-8) and anti-inflammatory (IL-10) cytokines released by macrophages cells are fundamental in acute inflammatory response (2-3 days) to destroy pathogens and help scaffold during regenerative process supporting the up-regulation of ECM and endothelial progenitor cells. Aim of this work was to evaluate the in vitro acute response induced by pre-optimized polymeric electrospun matrices (EL-Ms), after 3 days contact with macrophages (M0) and EL-Ms ability to modulate M1 and/or M2 macrophages polarization. Biological characterization included MTT, LDH and Live/Dead assays, immunological characterization by ELISA for cytokine-expression levels determination. Morphological characterization was carried out by Confocal Laser Scanning Microscopy and Scanning Electron Microscopy. The results showed an initial pro-inflammatory response (after 24 h) characterized by release of TNF-alfa, IL-6 and IL-8 cytokines. A preferential anti-inflammatory response was highlighted after 72 h, demonstrated by higher release of IL-10 and elongation of macrophages in contact with EL-Ms, that is typical of M2 cell polarization. EL-Ms could be used as eligible support to enhance tissue regeneration promoting an anti-inflammatory response., (Copyright © 2021. Published by Elsevier B.V.)

On March 11, 2020, WHO has defined the novel coronavirus disease SARS-CoV-2 (COVID-19) outbreak as a pandemic and still today continues to affect much of the world. Among the reasons for the rapid spread of SARS-CoV-2 infection, there is not only the high transmissibility of the virus, but also the role of asymptomatic or minimally symptomatic carriers. Therefore diagnostic testing is central to contain the global pandemic. Up to now real-time reverse transcriptase polymerase chain reaction (RT-PCR)-based molecular assays for detecting SARSCoV-2 in respiratory specimens is the current reference standard for COVID-19 diagnosis. Nasopharyngeal swab is the preferred choice for SARS-CoV-2 testing; however is not always a free of complications procedure. In patients with severe coagulopathies or diseases such as HHT, the risk of nosebleeding may be high. As in all those conditions like advanced stage sinonasal neoplasms or unfavorable anatomical characteristics, the nasopharyngeal swab may not be feasible. This work reports a safe and effective procedure of nasopharyngeal swab collection for COVID-19 testing, through the transoral way, in patients with contraindication to perform it transnasally. The procedure proved feasible and well tolerated. The discomfort for the patient is comparable with the execution of an oropharyngeal swab without exposing him to additional complications. In selected cases, the procedure described represents a valid alternative to nasopharyngeal swab performed transnasally. In particular, it allows reaching the area with the highest diagnostic sensitivity. Moreover it can be performed by Otolaryngology and, with adequate training, also by non-specialist staff., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background & Aims: Estimation errors associated with bioelectric impedance evaluation may affect the accuracy of body composition and its prognostic value. We evaluated the prognostic value of a new body composition parameter (Nutrigram®) obtained from bioimpedance vectorial analysis-derived body cell mass and its association with nutritional and functional status., Design: Data of Italian and German cancer patients observed prospectively until death were used. Multivariable models (adjusted for age, gender, hydration status, performance status, and disease's stage) were built in both cohorts to assess the association between body composition outcome parameters (low fat-free mass [FFM], <15 [females] and <17 [males] kg/m 2 ; low standardized phase angle [SPA], <-1.65; low Nutrigram®, <510 [females] and <660 [males] mg/24 h/m) and 1-year all-cause mortality, low body mass index (BMI; <20 [<70 years] and <22 [≥70 years] kg/m 2 ), clinically significant weight loss (WL; ≥10% in 6 months) and low handgrip strength (HG; <20 [females] and <30 [males] kg)., Results: Low Nutrigram® was independently associated with mortality in both Italian (HR = 1.84 [95%CI, 1.18-2.86]; P = 0.007) and German cohorts (HR = 1.52 [95%CI, 1.17-2.07]; P = 0.008). Low FFMI and low SPA did not predict survival in the German cohort. In patients with low Nutrigram®, worse nutritional and functional status were observed in both study populations. Performance of models addressing the study endpoints showed substantial consistency with both cohorts, particularly of those including low Nutrigram®., Conclusions: We validated a new prognostic body composition parameter, which is easier to interpret than standard nutritional parameters and may be useful for identifying cancer patients at nutritional risk, requiring early nutritional support., Competing Interests: Conflict of interest All Authors certify that there are no affiliations with or involvement in any organization or entity with a direct financial interest in the subject matter or materials discussed in the manuscript., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Introduction: The retrosigmoidal (RS) placement of the Bonebridge system (BB) has been advocated for cases of unfavourable anatomical or clinical conditions which contraindicate transmastoid-presigmoidal positioning. However, these disadvantageous conditions, combined with the considerable dimensions of the implant, may represent a challenge, especially for surgeons with no skull base experience. Moreover, the literature reports only limited experience concerning RS implantation of the BB system., Methods: A multicentre, retrospective study was conducted to analyse the surgical and functional outcomes of a wide population of patients undergoing RS placement of the BB system by means of a surgical technique specifically developed to overcome the intraoperative issues related to this surgery. Twenty patients with conductive or mixed hearing loss and single sided deafness were submitted to RS implantation of the BB system., Results: Audiological assessment concerning the measurement of the functional and effective gain by pure-tone audiometry (28 dB HL and -12.25 dB HL, respectively) and speech audiometry (24.7 dB HL and -21 dB HL, respectively) was conducted. A high overall subjective improvement of quality of life was recorded with the Glasgow Benefit Inventory questionnaire. No major complications, such as device extrusions or other conditions requiring revision surgery, were reported during the follow-up period (median: 42 months)., Conclusions: In our study, which has one of the largest cohort of patients reported in the literature, RS placement of the BB system was safe and effective. Our functional results showed comparable hearing outcomes with presigmoidal placement. The effective gain, rarely investigated in this field, may be the object of further research to improve our understanding of bone conduction mechanisms exploited by bone conduction hearing implants., (Copyright © 2021 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

Background: Human placenta is recognized as a valuable vascular microneurosurgery training model because of its abundant availability, ethical acceptance, and analogous vasculature with other vessels of the human body; however, human placenta laboratory preparation techniques are not well described in the literature. This study outlines a detailed and standardized laboratory protocol for preparation of a color-perfused human placenta model. Survey-based validation of the model is also reported herein., Methods: The protocol involved cleaning and cannulation of the umbilical vein and arteries, irrigation with heparin, and storage at 3°C or freezing at -18°C. Before use, arteries were perfused with carmine/cochineal, and veins were perfused with methylthioninium chloride. A questionnaire with 5 questions was administered to 40 participants among attending or resident neurosurgeons, otolaryngologists, and maxillofacial surgeons on 4 consecutive microsurgical courses to assess the reliability of the placenta model. Trainees were divided into 3 groups based on their experience. A χ 2 test was used to identify differences between groups., Results: Forty-two placentas were considered appropriate for training and were successfully perfused with dyes. Thirty-three participants completed the questionnaire, of which most, especially advanced and intermediate participants, indicated the placenta as a valuable, accurate, and reproducible model. No differences were observed among the groups., Conclusions: The human placenta is an excellent tool for vascular microneurosurgery laboratory training. Color perfusion enhances the reliability of this model, which was validated by most surgeons, regardless of their experience., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Isolated Eustachian tube osteomata are a very rare entity indeed, with the last case being reported in 1979. We describe a case of the otoscopic finding of a blue-yellowish eardrum and successive identification by computed tomography scan of an osteoma localized in the Eustachian tube. Clinical presentation and diagnostic and therapeutic phases in comparison with the literature will be discussed.