Botulinum toxin therapy: functional silencing of salivary disorders.

Botulinum toxin (BTX) is a neurotoxic protein produced by Clostridium botulinum, an anaerobic bacterium. BTX therapy is a safe and effective treatment when used for functional silencing of the salivary glands in disorders such as sialoceles and salivary fistulas that may have a post-traumatic or post-operative origin. BTX injections can be considered in sialoceles and salivary fistulas after the failure of or together with conservative treatments (e.g. antibiotics, pressure dressings, or serial aspirations). BTX treatment has a promising role in chronic sialadenitis. BTX therapy is highly successful in the treatment of gustatory sweating (Frey\u2019s syndrome), and could be considered the gold standard treatment for this neurological disorder

A higher Angiogenin expression is associated with a non-nuclear Maspin location in laryngeal carcinoma

Objectives. In numerous malignancies, angiogenin (ANG) and Maspin are important proangiogenic and antiangiogenic regulators, respectively. The aim of this study was to identify potential relationships between the biological roles of these two proteins in laryngeal squamous cell carcinoma (LSCC). Methods. Immunohistochemical staining for ANG and Maspin was performed on specimens from 76 consecutive LSCC patients treated with surgery alone, considering the subcellular pattern of Maspin expression. Univariate and multivariate statistical models were used for prognostic purposes. Results. On univariate analysis, a different level of ANG expression was seen for patients stratified by subcellular Maspin expression pattern: the mean ANG expression was higher in cases with a nonnuclear MASPIN expression than in those with a nuclear pattern (P=0.002). Disease-free survival (DFS; in months) differed significantly when patients were stratified by N stage (P=0.01). Patients whose Maspin expression was nonnuclear (i.e., it was cytoplasmic or there was none) had a significantly higher recurrence rate (P<0.001), and shorter DFS (P=0.01) than those with a nuclear Maspin pattern. The mean ANG expression was significantly higher in cases with loco-regional recurrent disease (P=0.007); and patients with an ANG expression 655.0% had a significantly shorter DFS than those with an ANG expression <5.0% (P=0.007). On multivariate analysis, ANG expression 655.0% was a significant, independent, negative prognostic factor in terms of DFS (P=0.041). Conclusion. Our results support the hypothesis that a higher ANG expression is associated with a nonnuclear Maspin expression pattern in patients with LSCC. Further studies are needed to clarify the relationship between the ANG and Maspin pathways, and their potential diagnostic and therapeutic role in LSCC

Contemporary Perspectives in Pathophysiology of Facial Nerve Damage in Oto-Neurological and Skull Base Surgical Procedures: A Narrative Review

During the last decades, neuro-otological surgery has progressively reduced functional morbidity, including facial nerve damage. However, the occurrence of this sequela may significantly impact on patients’ quality of life. The aim of this narrative review is to provide an update on the patho-physiological and clinical issues related to facial nerve damage in oto-neurological and skull base surgery, in the light of a comprehensive therapeutic and rehabilitative approach to iatrogenic disfunctions. The narrative review is based on a search in the PubMed, Scopus, andWeb of Science databases. In this surgical setting, the onset of intraoperative facial nerve damage is related to various aspects, mainly concerning the anatomical relationship between tumor and nerve, the trajectory of the surgical corridor, and the boundaries of the resection margins. Mechanisms related to stretching, compression, devascularization, and heating may play a role in determining intraoperative facial nerve damage and provide the patho-physiological basis for possible nerve regeneration disorders. Most of the studies included in this review, dealing with the pathophysiology of surgical facial nerve injury, were preclinical. Future research should focus on the association between intraoperative trauma mechanisms and their clinical correlates in surgical practice. Further investigations should also be conducted to collect and record intraoperative data on nerve damage mechanisms, as well as the reports from neuro-monitoring systems

Prognostic significance of serine-phosphorylated STAT3 expression in pT1-T2 oral tongue carcinoma

Objectives. Phosphorylated (activated) STAT3 (pSTAT3) is a regulator of numerous genes that play an essential part in the onset, development and progression of cancer; it is involved in cell proliferation and preventing apoptosis, and in invasion, angiogenesis, and the evasion of immune surveillance. This study aimed mainly to investigate the potential prognostic role of pSTAT3 expression in oral tongue squamous cell carcinoma (SCC). Methods. Phospho-ser727 STAT3 immunolabeling was correlated with prognostic parameters in 34 consecutive cases of pT1\u2013T2 tongue SCCs undergoing primary surgery. Computer-based image analysis was used for the immunohistochemical reactions analysis. Results. Statistical analysis showed a difference in disease-free survival (DFS) when patients were stratified by pN status (P=0.031). Most tumors had variable degrees (mean\ub1SD, 80.7%\ub123.8%) of intense nuclear immunoreaction to pSTAT3. Our findings rule out any significant association of serine-phosphorylated nuclear STAT3 expression with tumor stage, grade, lymph node metastasis, recurrence rate, or DFS. Conclusion. In spite of these results, it is worth further investigating the role of pSTAT3 (serine-and tyrosine-pSTAT3) in oral tongue SCC in larger series because preclinical models are increasingly showing that several anticancer strategies would benefit from STAT3 phosphorylation inhibition

β-Arrestin-1 expression and epithelial-to-mesenchymal transition in laryngeal carcinoma.

Aim: The novel primary end-point of the present study was to ascertain β-arrestin-1 expression in a cohort of consecutive patients with laryngeal squamous cell carcinoma (LSCC) with information available on their cigarette-smoking habits. A secondary end-point was to conduct a preliminary clinical and pathological investigation into the possible role of β-arrestin-1 in the epithelial-to-mesenchymal transition (EMT), identified by testing for E-cadherin, Zeb1, and Zeb2 expression, in the setting of LSCC. Methods: The expression of β-arrestin-1, E-cadherin, zeb1, and zeb2 was ascertained in 20 consecutive LSCCs. Results: Statistical analysis showed no significant associations between β-arrestin-1 and EMT (based on the expression of E-cadherin, Zeb1, and Zeb2). The combined effect of nicotine and β-arrestin-1 was significantly associated with a shorter disease-free survival ( P=0.01) in our series of LSCC. This latter result was also confirmed in an independent, publicly available LSCC cohort ( P=0.047). Conclusions: Further investigations on larger series (ideally in prospective settings) are needed before we can consider closer follow-up protocols and/or more aggressive treatments for patients with LSCC and a combination of nicotine exposure and β-arrestin-1 positivity in tumor cells at the time of their diagnosis. Further studies on how β-arrestin functions in cancer via different signaling pathways might reveal potential targets for the treatment of even advanced laryngeal malignancies

Voice parameters in children with cochlear implants: a systematic review and meta-analysis

ABSTRACT: Introduction: An intact auditory system is essential for the development and maintenance of voice quality and speech prosody. On the contrary hearing loss affects the adjustments and appropriate use of organs involved in speech and voice production. Spectro-acoustic voice parameters have been valuated in CI users, and the authors of previous systematic reviews on the topic concluded that preliminary Fundamental Frequency seemed the most reliable parameter to evaluate voice alterations in adult CI users. The main aim of this systematic review and meta-analysis was to clarify the vocal parameters and prosodic alterations of speech in pediatric CI users. Materials and methods: The protocol of the systematic review was registered on the PROSPERO database International prospective register of systematic reviews. We conducted a search of the English literature published in the period between January 1st 2005 and April 1st 2022 on the Pubmed and Scopus databases. A meta-analysis was conducted to compare the values of voice acoustic parameters in CI users and nonhearing-impaired controls. The analysis was conducted using the standardized mean difference as the outcome measure. A random-effects model was fitted to the data. Results: A total of 1334 articles were initially evaluated using title and abstract screening. After applying inclusion/exclusion criteria, 20 articles were considered suitable for this review. The age of the cases ranged between 25 to 132 months at examination. The most studied parameters were F0, Jitter, Shimmer and Harmoni Noise Ratio (HNR); other parameters were seldom reported. A total of 11 studies were included in the meta-analysis of F0, with the majority of estimates being positive (75%); the estimated average standardized mean difference based on the random-effects model was 0.3033 (95% CI: 0.0605 to 0.5462; p = 0.0144). For Jitter (0.2229; 95% CI: -0.1862 to 0.7986; p = 0.2229) and shimmer (0.2540; 95% CI: -0.1404 to 0.6485; p = 0.2068) there was a trend toward positive values without reaching statistical significance. Discussion and conclusions: This meta-analysis confirmed that higher F0 values have been observed in the pediatric population of CI users compared to age-matched normal hearing volunteers, whereas the parameters of voice noise were not significantly different between cases and controls. Prosodic aspects of language need further investigations. In longitudinal contexts, prolonged auditory experience with CI has brought voice parameters closer to the norm. Following the available evidence, we stress the utility of inclusion of vocal acoustic analysis in the clinical evaluation and follow-up of CI patients to optimize the rehabilitation process of pediatric patients with hearing loss

Application of Patients Reported Outcome measures in Cochlear Implant patients: implications for the design of specific rehabilitation programs

Introduction: Cochlear implants (CI) had been developed to enable a satisfying verbal communication, music experiences have remained in the background of research and development and consequently many CI users are dissatisfied by the music they listen to. Nonetheless, concise indications for clinicians to test music abilities and prescribe rehabilitation programs are still lacking. The main aim of the present study was to test the utility of the application of two different Patient Reporting Outcomes (PRO) measures in a group of CI users. A secondary objective was to identify items capable of driving the indication and design specific music rehabilitation programs for CI patients. Material and Methods: A consecutive series of 73 CI patients referred to the Audiology Unit - University of Padova - was enrolled from November 2021 to May 2022 and evaluated with audiological battery test and PRO measures: Musica e Qualità della Vita (MUSQUAV) and Nijmegen Cochlear Implant Questionnaire (NCIQ) Italian version. Results: The Reliability analysis showed good consistency between the different PRO measures, (Cronbach alpha = 0.873). After accounting for epidemiological and clinical variables, PRO measures showed a correlation with audiological outcomes in only one case (rho=-0.170 for NCIQ-T with CI-Pure Tone Average. A willingness for musical rehabilitation was present in 63% of patients, (Rehab Factor, mean value of 0.791±0.675). Conclusions: we support the role of the application of MUSQUAV and NCIQ to improve the clinical and audiological evaluation of CI patients. Moreover, we proposed a derivative item, called Rehab Factor, which could be used in clinical practice and future studies to clarify the indication and priority of specific music rehabilitation programs