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Objective: There are currently no guidelines for simultaneous vestibular schwannoma surgery and cochlear implantation. This paper therefore provides our experience and our results regarding predictive parameters of good hearing. Methods: Morphological appearance of the cochlear nerve after tumour resection was used as the main criterion for implantation in the case series. Patients were then divided into responders and non-responders to cochlear implantation, and potential outcome predicting factors were evaluated in the two groups. Results: Nine of the 16 patients showed a response to cochlear implantation. Pre-surgery serviceable hearing was significantly more common in the responder group, while no difference was found in the two groups for other variables. Conclusion: This study highlights how the morphological appearance of the cochlear nerve can be useful to predict the hearing outcome and indicates that satisfactory hearing results are closely related to pre-surgery serviceable hearing. [ABSTRACT FROM AUTHOR]

Background: The suprageniculate fossa (SGF) is located between the geniculate ganglion, the middle cranial fossa (MCF) and the anterior semicircular canal (ASCC). An endoscopic transcanal approach has been recently proposed to treat the different lesions in this area. The aim of the study is to describe the anatomical pathway of this approach by measuring the dimensions of its boundaries while checking their correlation with the pneumatization of the SGF area., Methods: This is a retrospective anatomical analysis of Cone Beam CT scans of 80 patients, for a total of 160 temporal bones analyzed. Two checkpoints were measured for the SGF route, as an internal and an external window. These are triangles between the MCF dura, the geniculate ganglion and the ASCC on parasagittal and axial planes. The pneumatization of the SGF was also assessed, classified and correlated with the measured dimensions., Results: The depth of the SGF was 7.5 ± 1.8 mm. The width of the external window was 7.5 ± 1.9, 5.6 ± 2.4 and 1.6 ± 1.6 mm for the posterior, middle and anterior points of measurement, respectively. The height of the internal window was 7.6 ± 1.2, 4.5 ± 1.5 and 1.7 ± 1.7 mm for the posterior, middle and anterior points of measurement, respectively. Type A pneumatization was found in 87 cases, type B in 34 and type C in 39. The degree of pneumatization directly correlated to the depth and height of the fossa., Conclusions: The suprageniculate approach route is defined by the internal and external windows which should be evaluated during a pre-surgery imaging assessment. The detailed anatomy of the approach and the novel classification of the pneumatization of the SGF are here described which may be useful to plan a safer procedure with minimal complications.

Background : Petrous apex cholesterol granulomas (PACGs) are benign inflammatory cystic lesions of the temporal bone. Usually, asymptomatic patients may develop symptoms as the lesions expand. The diagnosis is based on both CT and MRI scans and the management relies on "wait and scan" or surgery. This paper aims at evaluating surgical outcomes and proposing a CT-based classification and a management algorithm. Methods : Patients with PACGs who were surgically treated between 2014 and 2024 were included. Symptoms, imaging, approach type and complications were considered. CT scans were classified as Type A (preserved apex cellularity), Type B (erosion of the apex cellularity), and Type C (involvement of the noble structures bone boundaries). The possible connection of the lesion with the infracochlear, perilabyrinthine and sphenoidal cellularity was assessed. Results : Nineteen patients with symptoms like diplopia, headache and sensorineural hearing loss were included. According to our classification, 1/19 patients was Type A, 4/19 were Type B and 14/19 were Type C. Five patients underwent a total resection, seven a subtotal and seven a surgical drainage. Only two complications were recorded, and 17/19 patients showed symptom regression and stability during follow-up. Conclusions : While the management of PACGs is still controversial, according to our classification and surgical outcomes, Type A, being mostly asymptomatic, should be managed with "wait and scan", Type B should undergo surgery when symptoms are present, while Type C should always undergo surgery because of their invasiveness and potential complications. When possible, a drainage should be attempted; otherwise, a surgical resection is chosen, and its completeness depends on the preoperative general and hearing status.

Tauopathies such as Alzheimer's disease are characterized by aggregation and increased phosphorylation of the microtubule-associated protein tau. Tau's pathological changes are closely linked to neurodegeneration, making tau a prime candidate for intervention. We developed an approach to monitor pathological changes of aggregation-prone human tau in living neurons. We identified 2-phenyloxazole (PHOX) derivatives as putative polypharmacological small molecules that interact with tau and modulate tau kinases. We found that PHOX15 inhibits tau aggregation, restores tau's physiological microtubule interaction, and reduces tau phosphorylation at disease-relevant sites. Molecular dynamics simulations highlight cryptic channel-like pockets crossing tau protofilaments and suggest that PHOX15 binding reduces the protofilament's ability to adopt a PHF-like conformation by modifying a key glycine triad. Our data demonstrate that live-cell imaging of a tauopathy model enables screening of compounds that modulate tau-microtubule interaction and allows identification of a promising polypharmacological drug candidate that simultaneously inhibits tau aggregation and reduces tau phosphorylation., (© 2024. The Author(s).)

Alzheimer's Disease (AD) and Parkinson's Disease (PD) represent two among the most frequent neurodegenerative diseases worldwide. A common hallmark of these pathologies is the misfolding and consequent aggregation of amyloid proteins into soluble oligomers and insoluble β-sheet-rich fibrils, which ultimately lead to neurotoxicity and cell death. After a hundred years of research on the subject, this is the only reliable histopathological feature in our hands. Since AD and PD are diagnosed only once neuronal death and the first symptoms have appeared, the early detection of these diseases is currently impossible. At present, there is no effective drug available, and patients are left with symptomatic and inconclusive therapies. Several reasons could be associated with the lack of effective therapeutic treatments. One of the most important factors is the lack of selective probes capable of detecting, as early as possible, the most toxic amyloid species involved in the onset of these pathologies. In this regard, chemical probes able to detect and distinguish among different amyloid aggregates are urgently needed. In this article, we will review and put into perspective results from ex vivo and in vivo studies performed on compounds specifically interacting with such early species. Following a general overview on the three different amyloid proteins leading to insoluble β-sheet-rich amyloid deposits (amyloid β 1-42 peptide, Tau, and α-synuclein), a list of the advantages and disadvantages of the approaches employed to date is discussed, with particular attention paid to the translation of fluorescence imaging into clinical applications. Furthermore, we also discuss how the progress achieved in detecting the amyloids of one neurodegenerative disease could be leveraged for research into another amyloidosis. As evidenced by a critical analysis of the state of the art, substantial work still needs to be conducted. Indeed, the early diagnosis of neurodegenerative diseases is a priority, and we believe that this review could be a useful tool for better investigating this field.

Many techniques have been proposed to restore facial symmetry in facial nerve palsies. This study presents our surgical approach called Endoscopic Temporalis Tendon Extension (ETTE). After nasotracheal intubation, a 4 cm skin incision is made at the nasolabial fold. Under endoscopic view, the medial face of the masseter muscle is detached from the mandibular ramus. The coronoid process is then sectioned by Piezosurgery®. Finally, a fascia lata graft is suspended between the temporalis tendon and the orbicularis oris. ETTE is a mixed technique, with a static suspension component and a dynamic contraction one. The preservation of the temporalis muscle insertion in temporal fossa allows for an optimal contraction. A fascia lata graft is necessary for reasons of length. The scar produced by the nasolabial incision allows to recreate the missing nasolabial fold. The endoscopic assistance provides greater precision during the procedure and entails a shorter learning curve., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Objective: Diffusion of endoscopic techniques for the resection of ethmoid bone malignancies through a transcribriform approach (TA) has raised new challenges regarding reconstruction options to reduce post-operative complications. Although there is consensus on the advantages of vascularized flaps over free grafts for large defects, no standard protocol exists on reconstruction procedures. In addition, although the pedicled nasoseptal flap has been extensively discussed, few studies have been published on extranasal pedicled flaps. The aim of this manuscript is to provide a detailed description of a reconstruction technique for large anterior skull base defects with the pericranial flap as part of a multilayered reconstruction. Moreover, patients treated with this approach were retrospectively assessed for post-operative complications., Methods: A detailed description of the reconstruction procedure as performed in our departments is provided. Pictures depicting the main surgical steps are also included. In addition, preliminary functional results from a retrospective series of patients who underwent a TA and subsequent pericranial flap-based multilayer reconstruction for ethmoid roof malignancies between 2016 and 2022 at two institutional centers are reported., Results: 16 patients were included in the study. Nine patients (56.3%) underwent adjuvant radiotherapy. Two patients had a biochemically-confirmed postoperative CSF leak. Only one of the two patients required surgical revision. During follow-up (mean 13 months), no other early nor delayed complications were observed., Conclusion: A standardized surgical technique with pericranial flap as part of a multilayered reconstruction for large anterior skull base defects following resection of sinonasal malignancies is proposed, which appears to be a safe choice when endonasal flaps are not available., Level of Evidence: Level 4 Laryngoscope, 133:2942-2947, 2023., (© 2023 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Tau is a protein characterized by large structural portions displaying extended conformational changes. Unfortunately, the accumulation of this protein into toxic aggregates in neuronal cells leads to a number of severe pathologies, collectively named tauopathies. In the last decade, significant research advancements were achieved, including a better understanding of Tau structures and their implication in different tauopathies. Interestingly, Tau is characterized by a high structural variability depending on the type of disease, the crystallization conditions, and the formation of pathologic aggregates obtained from in vitro versus ex vivo samples. In this review, we reported an up-to-date and comprehensive overview of Tau structures reported in the Protein Data Bank, with a special focus on discussing the connections between structural features, different tauopathies, different crystallization conditions, and the use of in vitro or ex vivo samples. The information reported in this article highlights very interesting links between all these aspects, which we believe may be of particular relevance for a more informed structure-based design of compounds able to modulate Tau aggregation.

Introduction and Objectives: The aim of the present study is the assessment of exclusive endoscopic ear surgery for the management of primarily acquired pars tensa cholesteatoma, which is commonly linked to the failure of the Eustachian tube leading to the formation of retraction pockets., Materials and Methods: Patients suffering from primarily acquired pars tensa cholesteatoma, who underwent primary surgery in our clinic, between 2014 and 2018 were included in this retrospective study. The disease was classified according to the EAONO/JOS system. Exclusive endoscopic ear surgery was performed for patients without mastoid involvement, while a microscopic-endoscopic tympanoplasty was carried out in case of mastoid extension. We assessed the recidivism rate during the follow-up., Results: Cholesteatomas belonged to stage I in 28% of cases, to stage II in 68% and only one patient was stage III. Only a portion of the pars tensa was involved in 13 instances, the whole pars tensa in 3 and both the tensa and the flaccida in 9. 17 out of 25 patients underwent exclusive endoscopic ear surgery and 8 needed a combined approach. We discovered 1 recurrence and 6 residual diseases., Conclusions: With only one case of recurrence in our series, we showed how pars tensa cholesteatoma cannot be exclusively explained through Eustachian tube dysfunction, but also through a ventilation blockage between the Eustachian tube and other mesotympanic areas due to the formation of intratympanic folds. Endoscopic ear surgery proved highly effective in the control of recurrences and it should be considered the treatment of choice., (Copyright © 2022 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Artificial intelligence (AI) is currently being used to augment histopathological diagnostics in pathology. This systematic review aims to evaluate the evolution of these AI-based diagnostic techniques for diagnosing head and neck neoplasms., Materials and Methods: Articles regarding the use of AI for head and neck pathology published from 1982 until March 2022 were evaluated based on a search strategy determined by a multidisciplinary team of pathologists and otolaryngologists. Data from eligible articles were summarized according to author, year of publication, country, study population, tumor details, study results, and limitations., Results: Thirteen articles were included according to inclusion criteria. The selected studies were published between 2012 and March 1, 2022. Most of these studies concern the diagnosis of oral cancer; in particular, 6 are related to the oral cavity, 2 to the larynx, 1 to the salivary glands, and 4 to head and neck squamous cell carcinoma not otherwise specified (NOS). As for the type of diagnostics considered, 12 concerned histopathology and 1 cytology., Discussion: Starting from the pathological examination, artificial intelligence tools are an excellent solution for implementing diagnosis capability. Nevertheless, today the unavailability of large training datasets is a main issue that needs to be overcome to realize the true potential., (© 2022 The Author(s).)

Introduction: The pneumatization of the different regions of the temporal bone is strictly related to the age and the degree of development of the mastoid and the middle ear. Petrous apex pneumatization is the last step of the development of the petrous bone system. The subcochlear canaliculus is an anatomical cavity, originating in the space between the fustis and the finiculus, and connecting the round window area to the petrous apex. The aim of the present article is analyzing the trend of development of the subcochlear canaliculus pneumatization, classified through CT scan examination, in different age subgroups., Materials and Methods: We conducted a retrospective review of patients who underwent temporal bone CT scans between 2014 and 2019. Pediatric and adult patients were included and divided into different age subgroups. The subcochlear canaliculus was examined through coronal view scans at the level of the round window niche and classified into 3 different groups (A, B and C) according to the degree of pneumatization., Results: A total of 270 Petrous bone CT scans was analyzed. The percentage of type A subcochlear canaliculus was significantly higher in the pediatric population if compared to the adult population (p = 0.001326). As far as type B subcochlear canaliculus is concerned, the difference between children and adults was not statistically significant (p = 0.2378). On the other hand, type C subcochlear canaliculus was predominant in the adult population (p = 0.000256)., Conclusions: There is a constant increase in pneumatization of the subcochlear canaliculus from 0 to 19 years and then a progressive decrease. This discovery has relevant surgical implications and has to be borne in mind in particular for cholesteatoma surgery and cochlear implantation surgery in the age groups in which the subcochlear canaliculus is highly pneumatized., (© 2021. The Author(s), under exclusive licence to Springer-Verlag France SAS part of Springer Nature.)

Alpha-synuclein (αSyn) is a highly expressed and conserved protein, typically found in the presynaptic terminals of neurons. The misfolding and aggregation of αSyn into amyloid fibrils is a pathogenic hallmark of several neurodegenerative diseases called synucleinopathies, such as Parkinson's disease. Since αSyn is an Intrinsically Disordered Protein, the characterization of its structure remains very challenging. Moreover, the mechanisms by which the structural conversion of monomeric αSyn into oligomers and finally into fibrils takes place is still far to be completely understood. Over the years, various studies have provided insights into the possible pathways that αSyn could follow to misfold and acquire oligomeric and fibrillar forms. In addition, it has been observed that αSyn structure can be influenced by different parameters, such as mutations in its sequence, the biological environment (e.g., lipids, endogenous small molecules and proteins), the interaction with exogenous compounds (e.g., drugs, diet components, heavy metals). Herein, we review the structural features of αSyn (wild-type and disease-mutated) that have been elucidated up to present by both experimental and computational techniques in different environmental and biological conditions. We believe that this gathering of current knowledge will further facilitate studies on αSyn, helping the planning of future experiments on the interactions of this protein with targeting molecules especially taking into consideration the environmental conditions., 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 Bisi, Feni, Peqini, Pérez-Peña, Ongeri, Pieraccini and Pellegrino.)

Cyclic nucleotide phosphodiesterase type 4 (PDE4), which controls the intracellular level of cyclic adenosine monophosphate (cAMP), has aroused scientific attention as a suitable target for anti-inflammatory therapy of respiratory diseases. This work describes the development and characterization of pyridazinone derivatives bearing an indole moiety as potential PDE4 inhibitors and their evaluation as anti-inflammatory agents. Among these derivatives, 4-(5-methoxy-1 H -indol-3-yl)-6-methylpyridazin-3(2 H )-one possesses promising activity, and selectivity towards PDE4B isoenzymes and is able to regulate potent pro-inflammatory cytokine and chemokine production by human primary macrophages., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objectives: The current study aims at assessing the effectiveness of the guidelines set up by our clinic for the protection of patients and staff which enabled us to proceed with urgent and oncological surgery after the outbreak of the Covid-19 pandemic., Material and Methods: Our ENT department devised specific equipment to be worn by the staff for personal protection when dealing with Covid-19 patients both in aerosol generating and non-generating procedures. Moreover, restrictive measures were enforced both for the outpatient department and for the ward where only urgent practices were carried out and visitors were not allowed, while non-urgent elective surgery was postponed. A codified scheme was followed to perform tracheostomy procedure in Covid-19 positive testing patients on the part of 3 specific teams of 2 surgeons each, while the resident educational program was reorganized to limit the spread of the infection., Results: In about a couple of months (from March 8th to May 3rd) a relevant amount of medical tests and surgical procedures were carried out on non COVID-19 patients and a certain number of tracheostomies were performed on COVID-19 patients. Consequently, all the ENT personnel were checked and found negative. Also, all the patients in the ward were swab tested and chest X-rayed, only one had a positive outcome and was adequately handled and treated., Conclusion: Our ENT guidelines regarding personal protection equipment and multiple simultaneous diagnostic procedures have proved to be an essential instrument for the management of patients with both known and unknown COVID-19 status., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Studies concerning programmed death-ligand 1 (PD-L1) expression in precancerous lesions of head and neck (HN) region have shown variable results., Methods: We systematically reviewed the published evidence on PD-L1 expression in HN precancerous lesions., Results: Of 1058 original articles, 14 were included in systematic review and 9 in meta-analysis. The pooled estimate of PD-L1 expression was 48.25% (confidence interval [CI] 21.07-75.98, I 2 98%, tau2 0.18). PD-L1 expression appeared to be more frequent in precancerous lesions than in normal mucosa (risk ratio [RR] 1.65, CI 0.65-4.03, I 2 91%, tau2 0.82) and less frequent than in invasive squamous cell carcinoma (RR 0.68, CI 0.43-1.08, I 2 91%, tau2 0.22)., Conclusions: PD-L1 expression could reflect a point of balance between host immune response and cancer escape ability. High heterogeneity and moderate quality suggest that further studies with larger sample size and more rigorous case selection will allow more precise assessment of PD-L1 expression in HN precancerous lesions., (© 2020 Wiley Periodicals, Inc.)

Objective: The aim of this article is to study the role and advantages of combined microscopic/endoscopic procedures or exclusive endoscopic approaches in the treatment of petrous apex pathologies., Methods: The study was designed as a retrospective case series analysis. We included patients affected by pathologies of the petrous apex, who underwent microscopic/endoscopic-assisted or exclusive endoscopic procedures. Patient and pathology characteristics and surgical data (focusing on the involvement of the internal carotid artery (ICA) and facial nerve by the disease) were collected. Residual disease, detected through the endoscopic check, and the feasibility of endoscopic residual tumor removal were also evaluated. Finally, facial nerve and hearing functions were assessed pre- and postoperatively., Results: The records of 75 patients undergoing lateral skull base surgery for petrous apex lesions, from May 2009 to March 2019, were collected. In 17 out of 75 patients, an exclusive endoscopic procedure was possible. The remaining 58 patients underwent a combined microscopic/endoscopic approach. In 15 cases, residual disease was found and removed endoscopically at the end of the microscopic procedure; in eight cases, the residual disease was medial and/or inferior to the horizontal segment of the ICA, while in two cases, it was located in the fundus of the internal auditory canal. In five cases, it involved the labyrinthine segment of the facial nerve., Conclusion: Petrous apex surgery remains a traditional microscopic-based surgery, but the recent advent of endoscopic surgery has permitted an improvement in radicality minimizing the manipulation of neurovascular structures.