Challenges and Complications in the Management of Advanced Oropharyngeal Carcinoma: Role of Post-Mortem Diagnosis and Future Perspectives.

Oropharyngeal squamous-cell carcinoma (OPSCC) poses significant challenges in diagnosis, treatment, and management and has important medico-legal and forensic implications. In particular, the management of OPSCC and its treatment-related complications can often be challenging. In cases with advanced OPSCC, a loco-regional extension of the tumor can contribute to the destruction of oral cavity tissues, while the radiotherapy treatment can induce profound changes in tissue morphology and structure. These changes, which resemble tumor neoplasms and endovascular effects, are related to a higher risk of fatal bleeding, as reported in the case study illustrated, in which a hemorrhage occurred from a lingual artery, originating from an ulcerative, necrotic, hemorrhagic lesion on the tongue. Bleeding complications in OPSCC and prolonged radiotherapy are associated with high mortality and require comprehensive management strategies to improve survival and quality of life. Autopsy investigations, contributing to the definition of post-mortem diagnosis, can provide valuable insights into the pathogenetic mechanisms underlying bleeding and guide therapeutic decisions and preventive measures. The integration of autopsy and histopathological investigation into clinical practice should be considered as a necessary support to optimize the management of complications in advanced OPSCC patients, emphasizing the importance of a patient-centered approach and continued research.

Efficacy of tailor-made notched music training for primary tinnitus: A systematic review and meta-analysis.

OBJECTIVE: We systematically reviewed and meta-analyzed the efficacy of Tailor-Made Notched Music Training (TMNMT) for primary subjective tinnitus in adults. The main goal was to evaluate TMNMT's impact on tinnitus symptoms. METHODS: Following PRISMA guidelines, we included randomized and non-randomized trials. Studies considered involved adults with primary subjective tinnitus treated with TMNMT alone or combined with other therapies. Bias risk was assessed using the Cochrane RoB 2 and ROBINS-I tools. Comprehensive database searches were conducted, and relevant data were extracted and analyzed. RESULTS: Three studies (total: 99 TMNMT patients, 109 sound therapy) were meta-analyzed. Using THI scores, the Forest plot showed no significant difference in tinnitus distress between TMNMT and listening to music groups (p > 0.05), with low study heterogeneity (I2 = 0 %). CONCLUSION: While TMNMT offers a non-invasive approach with a potential to reduce tinnitus distress, it did not significantly outperform the only listening to music. More research is needed to optimize TMNMT for tinnitus management and to better document its safety profile.

A novel seated repositioning maneuver for geotropic lateral canal BPPV: efficacy and technique.

PURPOSE: This study introduces and evaluates the sitting lateral canal maneuver (SLCM), a novel seated repositioning technique for treating geotropic lateral canal benign paroxysmal positional vertigo (BPPV). METHODS: We conducted a retrospective chart review at the Hospital of Salerno, focusing on 26 patients diagnosed with geotropic LC-BPPV between 2021 and 2022. The SLCM was applied, and its efficacy was assessed based on the resolution of nystagmus and vertigo symptoms. A 95% confidence interval was calculated to estimate the success rate. RESULTS: The SLCM demonstrated a high success rate, with 22 out of 26 patients (approximately 85%, 22/26 patients) showing positive outcomes. The 95% confidence interval for the success rate ranged from approximately 65.02-100%. These findings suggest that SLCM is a potentially effective intervention for LC-BPPV, especially beneficial for patients who find traditional supine or lateral maneuvers uncomfortable. CONCLUSION: The SLCM represents a promising alternative to traditional BPPV maneuvers, especially for patients requiring a seated approach. While the initial results are encouraging, further research with larger sample sizes and longer follow-up periods is needed to validate its efficacy and explore its full potential in the management of LC-BPPV. LEVEL OF EVIDENCE: This study represents a Level IV source of evidence, as defined by the evidence-based practice guidelines. It is a retrospective chart review that involves a moderate cohort of patients diagnosed with geotropic horizontal positional nystagmus consistent with lateral canal benign paroxysmal positional vertigo (LC-BPPV). While the study provides valuable insights into the efficacy of the sitting lateral canal maneuver (SLCM) and contributes to the existing literature on BPPV management, it is important to note the inherent limitations associated with this level of evidence.

Role of Tumor-Infiltrating Lymphocytes and the Tumor Microenvironment in the Survival of Malignant Parotid Gland Tumors: A Two-Centre Retrospective Analysis of 107 Patients.

Background: This study aims to retrospectively investigate the prognostic significance of the tumor microenvironment, with a focus on TILs (tumor-infiltrating lymphocytes), in relation to survival in a large cohort of patients with parotid gland cancer, and it uses the method proposed by the International TILs Working Group in breast cancer. Methods: We included a cohort of consecutive patients with biopsy-proven parotid cancer who underwent surgery between January 2010 and September 2023. A retrospective review of medical records, including surgical, pathological and follow-up reports, was performed. The density of TILs was determined according to the recommendations of the International TILs Working Group for breast cancer. Results: A weak negative correlation (p = 0.3) between TILs and time of survival and a weak positive correlation (p = 0.05) between TILs and months of survival (high TILs were correlated with longer survival in months) were identified. High TILs were weakly negatively, but not statistically significantly p (0.7), correlated with the grading of tumor; this means that high TILs were associated with low-grade tumors. Conclusions: Contrary to previous preliminary reports, this retrospective work found no statistically significant prognostic role of TILs in parotid gland malignancies. This case series represents the largest cohort ever reported in the literature and includes all malignant histological types. Future larger molecular studies may be useful in this regard.

Post-operative radiotherapy in adenoid cystic carcinoma of salivary glands versus surgery alone: what is the evidence about survival and local control? A systematic review and meta-analysis.

BACKGROUND: Adenoid cystic carcinoma of the salivary glands is a relatively rare malignancy characterized by slow growth and a poor prognosis, and effective treatments remain challenging to identify. This systematic review, following the PRISMA guidelines, aimed to analyze the potential benefits of post-operative radiotherapy in terms of local control of recurrences and survival advantages when compared with surgery alone in patients with adenoid cystic carcinoma. METHODS: A comprehensive systematic review was conducted by searching the MEDLINE, Cochrane, EMBASE, and OVID databases from January 1999 to July 2022. The goal was to identify articles comparing surgery alone with surgery plus postoperative radiotherapy for adenoid cystic carcinoma of the salivary glands. Downs and Black Checklist was used to assess the methodological quality and risk of bias of each included study. The data analysis was performed using Review Manager version 5.4.1. RESULTS: This review included 8 studies comprising a total of 3103 patients, divided based on the analyzed outcomes. The pooled odds ratio for overall survival at 5 years was 0.87 (95% confidence interval 0.43-1.76, p = 0.70), and at 10 years was 1.23 (95% confidence interval 0.69-2.16, p = 0.48). In both cases, no statistically significant differences were observed. However, the pooled odds ratio for local control at 5 years was 3.37 (95% confidence interval 1.35-8.42, p = 0.009), providing strong support for the use of post-operative radiation. CONCLUSIONS: The findings from the meta-analysis suggest that post-operative radiotherapy significantly improves local control in patients with adenoid cystic carcinoma. However, there was no statistically significant increase in survival at 5 and 10 years. It is essential to note that the quality of the studies included in this meta-analysis ranged from fair to poor. To better clarify the indications for post-operative radiotherapy, future high-quality research is needed, particularly with improved stratification of patient groups. Additionally, it is important to recognize that achieving local control in adenoid cystic carcinoma is crucial for enhancing the overall quality of life for patients. We acknowledge that this review was not registered in the PROSPERO database, and the data pooling was conducted using a random effects model.

Enhancing the therapeutic potential of intravenous glycerol for Meniere's disease: Robust results from an extensive patient cohort.

INTRODUCTION: Meniere's disease (MD) is an idiopatic condition characterized by recurrent attacks of vertigo, hearing loss, tinnitus, and aural fullness, affecting quality of life. Intravenous glycerol has shown potential as a therapeutic option. This study evaluates its efficacy in a larger patient cohort. MATERIALS AND METHODS: Retrospective study with 168 patients having unilateral MD unresponsive to dietary restrictions. Intravenous 10 % glycerol with 0.9 % sodium chloride was administered for six months. Audio-vestibular assessments and questionnaires were used. RESULTS: Significant improvements in vertigo control observed. 7.1 % achieved complete control, and 58.3 % had substantial control. Quality of life measures improved, and audiometry thresholds remained unchanged. No major adverse events reported. DISCUSSION: Intravenous glycerol effectively controlled vertigo and improved MD patients' quality of life. Limitations include lack of a control group and a relatively short-term follow-up. Future prospects include randomized controlled trials and optimization of treatment protocols. CONCLUSION: Intravenous glycerol shows promise as a therapeutic option for MD, with notable improvements in vertigo control and quality of life. Further research is needed for validation and optimization.

Efficacy and preservation of hearing with low-dose gentamicin in unilateral meniere's disease: A clinical symptomatology-based study.

PURPOSE: Meniere's disease (MD), a disorder of the inner ear, presents numerous therapeutic challenges, and intratympanic (IT) gentamicin has been proposed for intractable cases. However, controversy regarding dosage and method persists. The purpose of this study was to assess the efficacy and safety of low-dose IT gentamicin on vertigo attacks in MD using a clinical symptomatology-based method, wherein administration was repeated only if vertigo attacks recurred, with a 2-week interval between injections. MATERIALS AND METHODS: This study included 88 patients with unilateral intractable MD. All patients received one to five IT injections with 0.5 ml of 10 mg of gentamicin (80 mg/2 ml) with an interval of 2 weeks between injections. Vertigo attacks were evaluated before and after therapy and categorized into classes A-F according to the 2015 Equilibrium Committee criteria. Audiovestibular assessments, including Pure Tone Audiometry and Vestibulo-Ocular Reflex evaluations, were performed. RESULTS: Before treatment, patients had an average of 4.4 vertigo attacks/month; after treatment, this average decreased to 0.52. The majority of patients (57 %) reached Class A or B vertigo control with five or fewer gentamicin injections. VOR gain was slightly affected on the healthy side and significantly reduced on the affected side. No hearing deterioration was found in any of the treated patients. CONCLUSIONS: Low-dose IT gentamicin administration based on clinical symptomatology can produce a satisfactory control of vertigo attacks after treatment. This protocol primarily affected the vestibular function, as demonstrated by the significant reduction in VOR gain on the affected side, while avoiding cochlear damage. The lack of adverse events and preservation of hearing underscore the safety and efficacy of this method. These findings have significant clinical implications, suggesting that a low-dose, clinical symptomatology-based gentamicin treatment regimen could be an effective and safe strategy for managing unilateral Meniere's disease in a larger population.

A Retrospective Multicenter Italian Analysis of Epidemiological, Clinical and Histopathological Features in a Sample of Patients with Acinic Cell Carcinoma of the Parotid Gland.

BACKGROUND: The acinic cell carcinoma (AciCC) of the parotid gland is a rare tumor with an indolent behavior; however, a subgroup of this tumor presents an aggressive behavior with a tendency to recur. The aim of this multicenter study was to identify and stratify those patients with AciCC at high risk of tumor recurrence. METHODS: A retrospective study was carried out involving 77 patients treated with surgery between January 2000 and September 2022, in different Italian referral centers. Data about tumor characteristics and its recurrence were collected. The histological specimens and slides were independently reviewed by a senior pathologist coordinator (L.C.) and the institution's local head and neck pathologist. RESULTS: The patients' age average was 53.6 years, with a female prevalence in the group. The mean follow-up was 67.4 months (1-258, SD 59.39). The five-year overall survival (OS) was 83.2%. The 5-year disease-free survival (DFS) was 60% (95% CI 58.2-61.7). A high incidence of necrosis, extraglandular spread, lymphovascular invasion (LVI), atypical mitosis, and cellular pleomorphism was observed in the high-risk tumors compared to the low-risk ones. CONCLUSION: AciCC generally had an indolent behavior, optimal OS, DFS with few cervical node metastases, and rare distant relapses. This multicenter retrospective case series provides evidence of the need for clinical-epidemiological-histological stratification for patients at risk of poor outcomes. Our results suggest that the correct definition of high-risk AciCC should include tumor size, the presence of necrosis, extraglandular spread, LVI, atypical mitosis, and cellular pleomorphism.

Different Prognostic Role of Soluble PD-L1 in the Course of Severe and Non-Severe COVID-19.

Understanding the link between COVID-19 and patient immune characteristics is crucial. We previously demonstrated that high levels of the soluble Programmed Death-Ligand1 (sPD-L1) at the beginning of the infection correlated with low lymphocyte number and high C-reactive protein (CRP), longer length of stay (LOS), and death. This study investigated whether sPD-L1 can be a prognosis biomarker during COVID-19. Severe and non-severe COVID-19 patients were enrolled at the University Hospital of Salerno. During hospitalization, at admission, and after 12-14 days, patients' data were collected, and sPD-L1 levels were measured by enzyme-linked immunosorbent assay. The peripheral lymphocyte number negatively correlated with the time of negativization (p = 0.006), length of stay (LOS) (p = 0.032), and CRP (p = 0.004), while sPD-L1 positively correlated with LOS (p = 0.015). Patients with increased sPD-L1 and lymphocyte number showed a shorter LOS than those with decreased sPD-L1 and lymphocyte number (p = 0.038) and those with increased sPD-L1 and decreased lymphocyte number (p = 0.025). Moreover, patients with increased sPD-L1 and decreased CRP had a shorter LOS than those with increased sPD-L1 and CRP (p = 0.034) and those with decreased sPD-L1 and CRP (p = 0.048). In conclusion, while at an early phase of COVID-19, sPD-L1 promotes an immune escape, later, it might act to dampen an excessive immune response, proving its role in COVID-19 prognosis.

Systematic Review of Management and Survival Outcome of Parotid Cancers with Lateral Skull Base Invasion.

Lateral skull base involvement from parotid cancers is a rare condition and is considered a poor prognostic indicator. The aim of this study was to systematically review the literature of parotid tumors with temporal bone invasion to analyze the survival outcome. A systematic literature review was performed in August 2022, without time limits, and 289 patients affected by parotid gland cancers and lateral skull base involvement were included. The most common symptoms in parotid tumors at the onset were indolent mass, facial weakness, pain, and hearing loss; the chi-square value is 23.1063, with a statistically significance (p = < 0.000121). The five most common histologies were adenoid cystic carcinoma, acinic cell carcinoma, mucoepidermoid carcinoma, adenocarcinoma, and squamous cell carcinoma. The facial nerve function after surgery showed statistically significance (functional vs. non-functional; chi-square was 91.7698, p = < 0.00001). Mean follow-up was 36.2 months (range 0.3-192). At the last follow-up, more patients died of disease (DOD; 60/289, 21%) than other causes (DOOC; 5/289, 2%). There is a statistically significant correlation between patients died for tumor (DOD) and patients died for other causes (DOOC) (p = < 0.0001), suggesting that the lateral skull base invasion negatively impacts on survival. Basing on the results of our systematic review, lateral skull base involvement from parotid recurrent/advance tumors should be considered a poor prognostic factor, as the majority of patients die due to this condition. It also would be necessary to have "clear"works, with full data (demographic, clinical, surgical data), and with a longer follow up, in order to assess the best treatment modality of these patients.

Pharyngocutaneous Fistula in Salvage Laryngectomy: Use of the Stapler Versus Manual Suturing Technique.

A pharyngocutaneous fistula (PCF) is the most common complication after salvage total laryngectomy (STL) with an incidence ranging from 5 to 73%, causing an increase in morbidity and delaying the patient's recovery. A surgical technique to prevent PCF formation is the use of the stapler to suture the pharyngeal mucosa.  We have reviewed the medical files of 91 patients who had undergone STL, dividing the patients into two groups (manual suture vs. stapler), based on the type of pharyngeal suture performed during the STL. We found 12/49 (24.5%) cases of a PCF in group A (manual) and 5/42 (11.9%) cases of a PCF in group B (stapler). There is a statistically significant difference between the two groups with the patients in group B presenting better results in terms of the reduction of the surgical time, the length of the hospital stay and also in the restarting of oral feeding. The advantages of mechanical suturing with the stapler are reduced surgical times, a lower PCF formation rate, which involves an early removal of the nasogastric tube, and reduced hospitalization times. Further studies with a larger case series will be necessary to confirm the results obtained and to standardize the surgical technique.

Correlation Between Air-Bone Gap and Vestibular Aqueduct Size in Enlarged Vestibular Aqueduct Syndrome: A Systematic Review.

The purpose of this review was to evaluate the air-bone gap with vestibular aqueduct size in enlarged vestibular aqueduct syndrome. According to the PRISMA guidelines we conducted a systematic review of the literature. Published international articles in English from 2000 to 2022 were screened, checking for studies that evaluated the air-bone gap of patients affected by enlarged vestibular aqueduct syndrome and the size of vestibular aqueduct. Data related to the hearing assessment and imaging investigation of enrolled participants were extracted. The chosen primary outcome measure was the correlation between air-bone-gap and vestibular aqueduct size. The database search allowed us to screen 485 articles and to select 5 articles discussing this topic for a total of 349 patients. Two studies showed a positive correlation between air-bone gap and vestibular aqueduct size, one only a trend and two no correlation. To date, it is not possible to draw conclusions whether or not there is a positive correlation between air-bone gap and vestibular aqueduct size in enlarged vestibular aqueduct syndrome. Higher quality studies would be conducted with standardized outcome measures to clarify the specific research question.

Practical recommendations for managing severe chronic rhinosinusitis with nasal polyps in the era of biologics.

Objective: We conducted a national survey to understand how rhinology practice has changed with the advent of biologics and how this affected patients with uncontrolled, severe chronic rhinosinusitis with nasal polyps (CRSwNP). We aimed to analyse the results of the survey and infer practical recommendations for clinical practice. Methods: A group of ear, nose, and throat specialists (ENTs) experienced in the management of CRSwNP developed a 74-question survey. ENTs from rhinology centres authorised to prescribe biologics in the context of the national health system were invited to answer it between 01/05/2022 and 31/07/2022. The responses underwent descriptive analyses, and the authors discussed the results and derived practical recommendations for clinical practice. Results: ENTs working in rhinology centres changed their practices coinciding with the advent of biologics. CRSwNP evaluations have become more complex because they involve diagnostic confirmation, determining the patients' immunologic profile, and other factors. We observed heterogenous behaviours in practice that may be conditioned by the novelty of the topic. The results of the survey were used to develop practical recommendations for ENTs and are summarised herein. Conclusions: Clinical practice in rhinology outpatient clinics has changed profoundly in the era of biologics. Our practical recommendations for clinicians working in rhinology centres are expected to help standardise practice and improve care.

Y-Columellar Strut Graft: A Method for Reconstructing the Nasal Tip in Primary and Revision Rhinoplasty.

SUMMARY: Several techniques have been proposed to modify tip shape and projection, both in congenital and in acquired nasal tip deformities. The authors describe a novel technique, the Y-columellar strut graft (Y-strut), which uses auricular cartilage to increase tip projection and restore contour in primary or revision rhinoplasty. Thirty-seven patients with congenital, acquired, or iatrogenic nasal tip malformation underwent reconstruction with Y-strut using short or long upper limbs ("wings"). The short wing variant was used to increase tip projection in primary rhinoplasty, and the long wing variant was used to corrected iatrogenic deformities of alar cartilages in revision rhinoplasty, improving contour and projection. Frontal, oblique, and lateral views before and after surgery were analyzed in blinded fashion at 1 year for tip shape and projection. Statistical analyses compared demographic characteristics, deformity type, and nasolabial angle before and after surgery to evaluate aesthetic outcome. All patients demonstrated improved nasal tip position. The Y-strut increased the nasolabial angle, reflecting tip rotation, and findings were independent of type or location of deformity ( P < 0.00001). No statistically significant differences were observed in comparisons of the short- versus long-wing technique. Three patients with congenital nasal tip malformations showed mild tip deviation at 1-year follow-up, and one had mild dorsal irregularity unrelated to grafting; no negative outcomes were observed in revision rhinoplasty patients. The Y-columellar strut graft is a reliable and versatile rhinoplasty technique using paired, symmetric grafts fashioned from auricular cartilage to correct tip deformities. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Specific local nasal immunotherapy: Single center experience on 324 patients.

OBJECTIVE: To evaluate the efficacy and safety of specific local nasal immunotherapy (LNIT) in patients with allergic rhinitis. MATERIALS AND METHODS: A retrospective single-center study of 324 patients with allergic rhinitis (191 allergic to mites, 133 allergic to Grarninaceae or Parietaria pollen) treated with specific LNIT was carried out. As control group, 158 patients without allergic rhinitis were enrolled. All patients were evaluated before and after 32 weeks of treatment by subjective analysis of their self-reported symptoms and by objective analysis of nasal provocation test, nasal resistance by anterior rhinomanometry, and mucociliary clearance time. RESULTS: Clinical efficacy of LNIT for allergy to mites and pollens was confirmed by the differences in the symptoms score between the active group and the placebo group. The nasal provocation test and the rhinomanometric analysis confirm the result with a difference statistically significant. No differnces in mucociliary clearance time were found. CONCLUSIONS: Specific LNIT is a valide alternative to subcutaneous and sublingual administration. It is effective, safe, well tolerated by the patient, it can be done at home with fewer systemic reactions.

Dynamics of nasopharyngeal tract phageome and association with disease severity and age of patients during three waves of COVID-19.

In December 2019, several patients were hospitalized and diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which subsequently led to a global pandemic. To date, there are no studies evaluating the relationship between the respiratory phageome and the SARS-CoV-2 infection. The current study investigated the phageome profiles in the nasopharyngeal swabs collected from 55 patients during the three different waves of coronavirus disease 2019 (COVID-19) in the Campania Region (Southern Italy). Data obtained from the taxonomic profiling show that phage families belonging to the order Caudovirales have a high abundance in the patient samples. Moreover, the severity of the COVID-19 infection seems to be correlated with the phage abundance.

Entorhinal Cortex and Persistent Olfactory Loss in COVID-19 Patients: A Neuroanatomical Hypothesis. Comment on Fiorentino et al. Correlations between Persistent Olfactory and Semantic Memory Disorders after SARS-CoV-2 Infection. Brain Sci. 2022, 12, 714.

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