Pembrolizumab-based first-line treatment for PD-L1-positive, recurrent or metastatic head and neck squamous cell carcinoma: a retrospective analysis.

BACKGROUND: The KEYNOTE-048 trial showed that pembrolizumab-based first-line treatment for R/M HNSCC led to improved OS in the PD-L1 CPS ≥ 1 population when compared to the EXTREME regimen. However, the R/M HNSCC real-world population is generally frailer, often presenting with multiple comorbidities, worse performance status and older age than the population included in phase III clinical trials. METHODS: This is a retrospective, single-centre analysis of patients with R/M HNSCC treated with pembrolizumab-based first-line treatment. RESULTS: From February 2021 to March 2023, 92 patients were treated with pembrolizumab-based first-line treatment. Patients treated with pembrolizumab-based chemoimmunotherapy had better ECOG PS and younger age than those treated with pembrolizumab monotherapy. Median PFS and OS were 4 months and 8 months, respectively. PFS was similar among patients treated with pembrolizumab-based chemoimmunotherapy and pembrolizumab monotherapy, while patients treated with pembrolizumab monotherapy had worse OS (log-rank p =.001, HR 2.7). PFS and OS were improved in patients with PD-L1 CPS > = 20 (PFS: log-rank p =.005, HR 0.50; OS: log-rank p =.04, HR 0.57). Patients with higher ECOG PS scores had worse PFS and OS (PFS, log-rank p =.004; OS, log-rank p = 6e-04). In multivariable analysis, ECOG PS2 was associated with worse PFS and OS. CONCLUSIONS: PFS in our real-world cohort was similar to the KEYNOTE-048 reference while OS was numerically inferior. A deeper understanding of clinical variables that might affect survival outcomes of patients with R/M HNSCC beyond ECOG PS and PD-L1 CPS is urgently needed.

Polycystic Ovary Syndrome and Alteration of Vocal Function: A Systematic Review and Meta-Analysis.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a common hormonal disorder among young women, correlated with hyperandrogenism. Among the symptoms of PCOS, vocal alterations are quite unknown. Dysphonia may be related to hyperandrogenism, and there is no consensus about its prevalence and the severity of vocal disorders, which can cause noticeable discomfort. METHODS: A systematic review of the literature was conducted. Four studies on PCOS that evaluated the phonatory system were included for a total of 174 patients (96 PCOS, 78 controls), and a meta-analysis on comparable data was performed. RESULTS: Four studies evaluated parameters related to vocal symptomatology, altered audiometric examination, and findings at the laryngoscopy in patients affected by PCOS versus controls. Although the individual studies showed increased incidence of alterations and a tendency to develop speech fatigue in women with PCOS, when the results of studies were pulled in meta-analysis, the overall difference was not statistically significant. The studies themselves were very different from each other; therefore, it is hard to draw any firm conclusions. DISCUSSION: The aim of this study was to assess the prevalence of vocal alterations, the correlation with hyperandrogenism, the quality of life, and the voice changes after starting a therapy for PCOS. The present meta-analysis failed to find any difference in terms of PCOS and control cohort. However, the lack of high-quality studies makes it difficult to draw firm conclusions. New and larger studies or big population program data are therefore warranted.

Clinico-histopathological review of 255 patients who underwent parotidectomy for pleomorphic adenoma: a 10-year retrospective study-a proposal for an optimal diagnostic and therapeutic algorithm for patients with recurrent pleomorphic adenoma.

PURPOSE: Pleomorphic adenoma (mixed tumor) is the most common neoplasm of the parotid gland and one of the most frequent types of salivary gland tumor, generally with benign behavior and relatively slow growing. The adenomas could arise from the superficial, deep or from both superficial and deep parotid's lobes. METHODS: The aim of this review is to retrospectively analyze the surgical management of patients with pleomorphic adenoma of the parotid gland performed at the Department of Otorhinolaryngology (Department of Sense Organs of "Azienda Policlinico Umberto I" in Rome), from 2010 to 2020, with a focus on the percentage of recurrence and on the complication related to surgery to suggest an optimal diagnostic and therapeutic algorithm for patients with recurrent pleomorphic adenoma. The analysis of the complications observed in case of different surgical approaches was performed using the X2 test. RESULTS: The choice of a surgical approach (superficial parotidectomy-SP, total parotidectomy-TP, extracapsular dissection-ECD) depends on several elements, such as the location and the size of the adenoma, the availability of existing technical facilities and the professional experience of the surgeon. A transient facial palsy was present in 37.6%, 2.7% reported a permanent facial nerve palsy, 1.6% developed a salivary fistula, 1.6% a post-operative bleeding and 2.3% showed Frey Syndrome. CONCLUSION: The surgical management of this benign lesion is required, even in asymptomatic cases, to prevent the progressive growing and to reduce the risk of malignant transformation. The goal of surgical excision is to obtain the complete resection to minimize the risk of tumor recurrence and avoiding facial nerve disability. Therefore, an accurate preoperative study of the lesion and the choice of the most appropriate surgical treatment are essential to minimize the rate of recurrence.

Neoadjuvant chemotherapy and transoral robotic surgery for the posterior pharyngeal wall carcinoma.

BACKGROUND: The squamous cell carcinoma (SCC) of the posterior pharyngeal wall (PPW) is associated with poor oncological outcomes based on current literature data. We reported the preliminary outcomes of a potential new treatment protocol based on neoadjuvant chemotherapy (NCT) and transoral robotic surgery (TORS). METHODS: A retrospective single-center case series was performed including a total of 20 patients diagnosed with a SCC of the PPW between October 2010 and September 2021. All patients successfully completed TORS with neck dissection after NCT. Adjuvant treatment was performed in the presence of adverse pathologic features. Loco-regional control (LRC), overall survival (OS), and disease-specific survival (DSS) were defined as the time from surgery to tumor recurrence or death, as appropriate. Survival estimates were calculated by Kaplan-Meier analysis. Surgical data and post-operative functional outcomes were also reported. RESULTS: Estimated 3-year LRC, OS, and DSS rates (95% Confidence interval) were 59.7% (39.7-89.6), 58.6% (38.7-88.8), and 69.4% (49.9-96.6). The median hospital stay was 21 days (IQR 17.0-23.5). Oral diet and decannulation were achieved after a median of 14 days (IQR 12.0-15.0). Feeding tube and tracheostomy dependence after 6 months was observed in 3 (15%) and 2 (10%) patients, respectively. CONCLUSIONS: The use of NCT followed by TORS for PPW SCC treatment appears to have good oncological and functional outcomes for both early and locally advanced cancers. Further randomized trials and site-specific guidelines are needed.

Molecular Pathology, Oxidative Stress, and Biomarkers in Obstructive Sleep Apnea.

Obstructive sleep apnea syndrome (OSAS) is characterized by intermittent hypoxia (IH) during sleep due to recurrent upper airway obstruction. The derived oxidative stress (OS) leads to complications that do not only concern the sleep-wake rhythm but also systemic dysfunctions. The aim of this narrative literature review is to investigate molecular alterations, diagnostic markers, and potential medical therapies for OSAS. We analyzed the literature and synthesized the evidence collected. IH increases oxygen free radicals (ROS) and reduces antioxidant capacities. OS and metabolic alterations lead OSAS patients to undergo endothelial dysfunction, osteoporosis, systemic inflammation, increased cardiovascular risk, pulmonary remodeling, and neurological alterations. We treated molecular alterations known to date as useful for understanding the pathogenetic mechanisms and for their potential application as diagnostic markers. The most promising pharmacological therapies are those based on N-acetylcysteine (NAC), Vitamin C, Leptin, Dronabinol, or Atomoxetine + Oxybutynin, but all require further experimentation. CPAP remains the approved therapy capable of reversing most of the known molecular alterations; future drugs may be useful in treating the remaining dysfunctions.

SMN Deficiency Destabilizes ABCA1 Expression in Human Fibroblasts: Novel Insights in Pathophysiology of Spinal Muscular Atrophy.

The deficiency of survival motor neuron protein (SMN) causes spinal muscular atrophy (SMA), a rare neuromuscular disease that affects different organs. SMN is a key player in RNA metabolism regulation. An intriguing aspect of SMN function is its relationship with plasma membrane-associated proteins. Here, we provide a first demonstration that SMN affects the ATP-binding cassette transporter A1, (ABCA1), a membrane protein critically involved in cholesterol homeostasis. In human fibroblasts, we showed that SMN associates to ABCA1 mRNA, and impacts its subcellular distribution. Consistent with the central role of ABCA1 in the efflux of free cholesterol from cells, we observed a cholesterol accumulation in SMN-depleted human fibroblasts. These results were also confirmed in SMA type I patient-derived fibroblasts. These findings not only validate the intimate connection between SMN and plasma membrane-associated proteins, but also highlight a contribution of dysregulated cholesterol efflux in SMA pathophysiology.

Neurons, Nose, and Neurodegenerative Diseases: Olfactory Function and Cognitive Impairment.

Olfactory capacity declines with aging, but increasing evidence shows that smell dysfunction is one of the early signs of prodromal neurodegenerative diseases such as Alzheimer's and Parkinson's disease. The study of olfactory ability and its role in neurodegenerative diseases arouses much interest in the scientific community. In neurology, olfactory impairment is a potential early marker for the onset of neurodegenerative diseases, but the underlying mechanism is poorly understood. The loss of smell is considered a clinical sign of early-stage disease and a marker of the disease's progression and cognitive impairment. Highlighting the importance of biological bases of smell and molecular pathways could be fundamental to improve neuroprotective and therapeutic strategies. We focused on the review articles and meta-analyses on olfactory and cognitive impairment. We depicted the neurobiology of olfaction and the most common olfactory tests in neurodegenerative diseases. In addition, we underlined the close relationship between the olfactory and cognitive deficit due to nasal neuroepithelium, which is a direct extension of the CNS in communication with the external environment. Neurons, Nose, and Neurodegenerative diseases highlights the role of olfactory dysfunction as a clinical marker for early stages of neurodegenerative diseases when it is associated with molecular, clinical, and neuropathological correlations.

The RNA-Binding Protein SMN as a Novel Player in Laryngeal Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) arises from the mucosal epithelium in the oral cavity, pharynx, sino-nasal region, and larynx. Laryngeal squamous cell carcinoma (LSCC) represents one-third of all head and neck cancers. Dysregulated RNA-related pathways define an important molecular signature in this aggressive carcinoma. The Survival Motor Neuron (SMN) protein regulates fundamental aspects of the RNA metabolism but, curiously, its role in cancer is virtually unknown. For the first time, here, we focus on the SMN in the cancer context. We conducted a pilot study in a total of 20 patients with LSCC where the SMN was found overexpressed at both the protein and transcript levels. By a cellular model of human laryngeal carcinoma, we demonstrated that the SMN impacts cancer-relevant behaviors and perturbs key players of cell migration, invasion, and adhesion. Furthermore, in LSCC we showed a physical interaction between the SMN and the epidermal growth factor receptor (EGFR), whose overexpression is an important feature in these tumors. This study proposes the SMN protein as a novel therapeutic target in LSSC and likely in the whole spectrum of HNSCC. Overall, we provide the first analysis of the SMN in human cancer.

Accuracy of Dysphagia Standard Assessment (DSA®) bedside screening test: a flowchart for patient eligibility.

BACKGROUND: Oropharyngeal dysphagia (OD) screening tests have improved patient management; however, the complex applicability and high percentage of false negatives do not allow these tests to be considered completely reliable if not supported by an instrumental investigation. The aim of the present study is to evaluate an OD screening test, the Dysphagia Standard Assessment (DSA®) with different volumes and viscosities. MATERIALS AND METHODS: Prospective study of 72 patients evaluated for suspected OD through a double-blind methodology conducted by two operators. All patients underwent fiberoptic endoscopic evaluation of swallowing (FEES) as a reference test and a separate DSA® test. DSA® was performed by administering boluses with different viscosities, with the signal of interruption of the test being: onset of the cough reflex, wet voice after swallowing, and/or desaturation of O2 ≥ 5%. The Penetration-Aspiration Scale (PAS) was evaluated by FEES. The cut-off identified to diagnose OD was PAS ≥ 3. RESULTS: The test showed an accuracy of 82%, a sensitivity of 0.93 (95% C.I. 0.84-0.97), and a specificity of 0.78 (95% C.I. 0.67-0.87); positive predictive value 0.55 (95% C.I. 0.43-0.67); negative predictive value 0.97 (95% C.I. 0.90-0.99), positive likelihood ratio 4.37 (95% C.I. 3.6-5.2); likelihood negative ratio 0.08 (95% C.I. 0.06-0.09). CONCLUSIONS: According to the preliminary results, the test showed good outcomes in determining the presence or absence of OD with a wide spectrum of applicability with some limitations that could be overcome by the selection of a target population. For this reason, a flowchart to address patient eligibility was developed.

Interpretation of the mucous plug through sialendoscopy.

OBJECTIVE: The purpose of this manuscript is to highlight the behaviour of mucus inside the ducts of the major salivary glands, in presence of typical pathologies, through images obtained with sialendoscopy. SUBJECT: The authors present and comment on some sialendoscopies that show mucous plug in the ducts of the major salivary glands. RESULTS: In primary Sjogren's syndrome, mucous plugs confirm the qualitative anomaly of the mucins and acidification saliva. Instead, salivary calculations behave like foreign bodies that generate mechanical pressure and friction on the duct walls of major salivary glands, so mucus deposits in the duct in its defence; in case of infected stone, mucous plugs are formed also with the function of protecting the ducts from the aggression of germs. During sialadenitis, there is a conflict between mucus and bacteria which explains sialendoscopic evidence such as white duct walls and mucous plugs. CONCLUSIONS: The study of the salivary ducts through sialendoscopy often confirms the clinical diagnosis or hypothesize it. During its execution, it is necessary not only to liberate the ducts of the major salivary glands but also analyse the appearance of the mucous plugs and the ductal walls as they are useful to guide the physician towards diagnosis.

Barbed reposition pharyngoplasty (BRP) in obstructive sleep apnea treatment: State of the art.

PURPOSE: In this paper, we perform a systematic review that discusses the state of the art and evolution on the barbed reposition pharyngoplasty (BRP) in the velo-pharyngeal surgery. Clinical evidence and published outcomes of this surgical technique are reported and discussed. MATERIALS AND METHODS: We performed a systematic review of the current literature through the analysis of the last 10 years of literature on barbed palate surgery. Study design, number of patients enrolled, inclusion criteria, pre- and posttreatment outcomes (AHI, ODI), surgical success rate, follow-up time and complication has been collected and reported. RESULTS: 15 studies for a total of 1531 patients, out of which 1061 underwent barbed reposition pharyngoplasty. Five trials were uncontrolled prospective studies (215 patients, 14% of total), nine were retrospective studies (1266 patients, 82,6% of total), and one randomized prospective clinical trial (RCT) (50 patients, 3,32% of total). All analyzed studies reported good outcomes after BRP surgery. Average preoperative values of AHI and ODI reduced in all studies considered with a significative statistical difference between preoperative and postoperative values (p < 0.05 in all cases). The postoperative surgical success rate ranged between 65.4 and 93% of cases. There were no significant intra-operative or post-operative complications in all studies considered in this systematic review. CONCLUSIONS: Barbed reposition pharyngoplasty has proven to be an easy to learn, quick, safe and effective new palatopharyngeal procedure, that can be used in a single level surgery or as a part of multilevel procedures.

Voice quality after transoral CO2 laser microsurgery (TOLMS): systematic review of literature.

PURPOSE: Transoral laser microsurgery (TOLMS) with carbon dioxide is a safe approach for laryngeal carcinoma. In literature there are three main methods for evaluating speech outcomes: acoustic and aerodynamics analysis, perceptual evaluation and patient-reported outcomes (PROs). The aim of this study was to systematically review the literature about the voice quality outcomes of TOLMS according to type of cordectomy. METHODS: A systematic literature review was performed and all the results until December 2021 were extrapolated. We evaluated the acoustic and aerodynamics parameters (fundamental frequency, harmonics to noise ratio, jitter, shimmer and maximum phonation time), perceptual data (GRBAS scale) and patient-related outcomes (VHI scale). RESULTS: 24 studies met the inclusion criteria for a total number of 1207 patients enrolled. The number for each type of cordectomy are: 287 type I (23.78%), 311 type II (25.78%), 328 type III (27.14%), 129 type 4 (10.69%) and 152 type V (12.60%). Patients are grouped according to the type of cordectomy in: limited cordectomy (type I and II) and extended cordectomy (types III-IV-V). The difference between two groups is statistically significative in terms of acoustic analysis, perceptual data and patient-related outcomes (p < 0.05). CONCLUSIONS: Patients who underwent type I or II cordectomy have significantly better quality of voice in terms of VHI, perceptual voice quality evaluations and acoustic parameters compared to type III, IV and V cordectomies. The effect of TOLMS on the voice should depend from the extent of the resection and in particular from the scar of the vocal muscle.

Carcinosarcomas of the larynx: systematic review of the literature of a rare nosologic entity.

PURPOSE: Carcinosarcoma, also known as Spindle Cell Carcinoma (SpCC), is a rare type of malignant tumor. Generally, this type of pathology occurs in the urogenital tract, the gastrointestinal tract, respiratory tract and mammary gland; in the larynx, SpCC represents only 2-3% of all malignancies. Due to its rarity, there is currently no generally acceptable treatment guideline for this disease. The aim of this study was to systematically review the literature of SpCC of larynx and report epidemiologic, clinicopathologic and main therapeutic approaches for this entity. METHODS: A systematic literature review was performed using MEDLINE, EMBASE, PubMed and Scopus databases. For this review, the results were extrapolated in the period between January 1990 to September 2020. Data extraction was performed using a standard registry database. The clinical and pathological staging were recalculated according to the Eight Edition of AJCC Cancer Staging Manual and statistical analyses were performed using SPSS Version 25.0. RESULTS: A total of 111 patients affected by laryngeal carcinosarcoma were included. From our review arises that surgery is the main treatment for primary laryngeal carcinosarcoma. In this way, various techniques such as minimally invasive laryngoscopy excision, laser CO2 cordectomy, partial laryngectomy (vertical and horizontal) and total laryngectomy. The role of radiotherapy is still controversial. The overall survival (OS) for T1 stage tumor at 5 years of follow-up is 82.9%, the OS for T2 and T3 tumor is 74% and 73.4%. The OS at 5 years of follow-up is 91.7% for supraglottic tumor, 69.3% for glottic tumor and 50% for transglottic site. Subglottic site is described in only 2 cases [12-13], so the OS at 5 years is not statistically significant. The 5-year overall survival in patients without lymph nodes involvement (N0) is 90.2%, 66.7% and 50%, respectively, for N1 and N2 lesions. CONCLUSION: Primary laryngeal carcinosarcoma is a very rare malignancy. There are no clear guidelines in the management but in the literature, surgery is described as the best modality of therapy; radiation only can be a reasonable alternative with controversial efficacy. The most important prognostic factor is the nodal metastasis.

Listening comprehension in profoundly deaf children with cochlear implants: the role of auditory perception and foundational linguistic and cognitive skills.

PURPOSE: The aim of the study was to investigate the listening comprehension (LC) skills in deaf and hard of hearing children (DHH) using cochlear implants (CI). Besides, personal and audiological variables that could influence the levels of competence reached were analyzed. METHODS: Thirty-four children using CI were enrolled. LC skills were assessed through the standardized Italian test "Comprensione Orale-Test e Trattamento" (CO-TT). A univariate analysis was conducted to compare LC with gender, listening mode (unilateral or bilateral), maternal level of education and family income. A bivariate analysis was performed to search possible connections between children's performances and their individual characteristics, audiological conditions, and language levels. Finally, a multivariate analysis was performed using a stepwise hierarchical linear regression model which included all variables whose p value resulted ≤ 0.05. RESULTS: Twenty-one children using CI (61.8%) showed adequate performances in terms of chronological age, while 13 (38.2%) showed difficulties in LC. Maternal level of education, age at diagnosis and non-verbal cognitive level accounted for 43% of the observed variance. Auditory attention skills explained an additional 15% of variance. Morphosyntactic comprehension added a further 12% of variance. CONCLUSION: CI can really help many DHH children to reach adequate LC skills, but in some cases difficulties remain. Factors influencing LC need to be early investigated and considered when planning an appropriate rehabilitative intervention.

Diagnostic performance of nasal cytology.

PURPOSE: Nasal pathologies are characterized by a symptomatology that hardly allows to distinguish allergic rhinitis (AR), non-allergic rhinitis (NAR), and chronic rhinosinusitis (CRS). Nasal cytology (NC) has shown increasing importance in helping the clinician to differentiate the various phenotypes of rhinitis. NC allows us to evaluate nasal cellularity by distinguishing AR and various types of NAR. The objective of the study is to assess the diagnostic performance of the NC by evaluating its sensitivity, specificity, and predictive value. METHODS: We recruited 387 patients with persistent rhinitis symptoms, and nasal cytology was performed. The rhinocytogram was obtained by reading for fields and the cellular count was made using quantitative and semi-quantitative grading together. RESULTS: Two hundred and fifteen patients (55.5%; 38 had acute rhinitis, 24 acute sinusitis, 153 chronic rhinosinusitis) out of 387 referred nasal symptoms. Cytological specimen showed a mean of 94 ± 4% ciliated cells, 29 ± 0.2% mucinous cells, 16 ± 0.1% neutrophils, 11 ± 0.08% eosinophils, 4 ± 0.03 lymphocytes, 4 ± 0.03% mast cells, and 4 ± 0.01% other cells. NC was positive in 271 cases (70%). After revision of medical history, 153 patients (39%) were considered positive for NAR. Test sensibility was 100% (95% CI 97-100), specificity was 49.6% (95% CI 43-56%). Positive predictive value (PPV) was 56% (95% CI 50-62%), and negative predictive value (NPV) was 100% (95% CI 96-100%). The positive likelihood ratio was 1.98 (95% CI 1.75-2.25). Accuracy of the test was 69.5% (95% CI 64.6-74.0%). CONCLUSION: Our data showed ability to identify the true-positive patients with NAR but a low ability to identify the true-negative patients, with a global accuracy of 69.5%.

Open partial horizontal laryngectomy for T2-T3-T4a laryngeal cancer: oncological outcomes and prognostic factors of two Italian hospitals.

PURPOSE: The purpose of this study was to analyse the oncologic results of open partial horizontal laryngectomy (OPHL) and to assess the prognostic factors that could affect the survival of patients affected by T2, T3 and T4a laryngeal cancer. Using this data, we aim to identify clinical criteria to select patients amenable to conservative surgery, and to facilitate a more targeted approach in the management of advanced laryngeal cancer. METHODS: A retrospective study was performed in patients who underwent OPHL type II for laryngeal squamous cell carcinoma from January 2005 to December 2018. We analysed a total of 170 patients; 21(12.36%) cases were staged as pT2, 116 (68.23%) as pT3 and 33 (19.41%) as pT4a. RESULTS: Five-year overall survival (OS) was 80.9%, 79.3%, 70.4% for T2, T3 and T4 respectively. Disease-specific survival (DSS) was 90.4%, 85.3% and 77.4%. Posterior tumour extension, perineural invasion and N status showed to considerably influence survival in both uni- and multivariate analyses. CONCLUSION: The oncological outcomes from our study show that OPHL for advanced laryngeal cancer can guarantee a high percentage of success. Accurate patient selection is of utmost importance to differentiate advanced disease amenable to conservative surgery, and treatment options should consider selected criteria based on tumour and patient features.

Impact of COVID-19 pandemic on the incidence of otitis media with effusion in adults and children: a multicenter study.

PURPOSE: To compare and analyze the incidence of otitis media with effusion (OME), before and during the COVID-19-related pandemic period, to evaluate the effects of the social changes (lockdown, continuous use of facial masks, social distancing, reduction of social activities) in the OME incidence in children and adults. METHODS: The number of diagnosed OME in e five referral centers, between 1 March 2018 and 1 March 2021, has been reviewed and collected. To estimate the reduction of OME incidence in children and adults during the COVID-19 pandemic period the OME incidence in three period of time were evaluated and compared: group 1-patients with OME diagnosis achieved between 1/03/2018 and 01/03/2019 (not pandemic period). Group 2-patients with OME diagnosis achieved between 1/03/2019 and 1/03/2020 (not pandemic period). Group 3-patients with OME diagnosis achieved between 1/03/2020 and 1/03/2021 (COVID-19 pandemic period). RESULTS: In the non-pandemic periods (group 1 and 2), the incidence of OME in the five referral centers considered was similar, with 482 and 555 diagnosed cases, respectively. In contrast, the OME incidence in the same centers, during the pandemic period (group 3) was clearly reduced with a lower total number of 177 cases of OME estimated. Percentage variation in OME incidence between the first non-pandemic year considered (group 1) and the pandemic period (group 3) was-63, 3%, with an absolute value decrease value of-305 cases. Similarly, comparing the second non-pandemic year (group 2) and the pandemic year (group 3) the percentage variation of OME incidence was-68, 1% with an absolute value of-305 cases decreased. CONCLUSIONS: Our findings showed a lower incidence of OME during the pandemic period compared with 2 previous non pandemic years. The drastic restrictive anti-contagion measures taken by the Italian government to contain the spread of COVID-19 could have had a positive impact on the lower OME incidence during the last pandemic year.

Treatment of Benign Lesion of Levels I or II of the Parotid Gland: Long Term Results of Partial Superficial Parotidectomy.

ABSTRACT: The correct surgical approach to benign parotid gland tumors is still matter of debate, it should be chosen considering the possibility of local recurrence or facial nerve complications in case of "not necessary" facial nerve dissection. In the era of minimally invasive surgery, more sparing approaches such as extracapsular dissection or partial superficial parotidectomy (PSP) are gaining popularity. The aim of the study is to present surgical results and long-term outcomes of PSP (level i or ii) in a large group of patients. Six hundred fifty-one patients who underwent parotid surgery between 2004 and 2020 were initially considered. Five hundred forty patients with benign lesions treated with PSP, enucleation, ECD were enrolled. Clinical features, surgical data, postoperative scarring, seroma, dehiscence, neuroma, outcomes as Frey syndrome, and delayed facial nerve dysfunction have been evaluated. 65.5% PSP, 25.2% enucleation, and 9.2% extracapsular dissection. No statistical difference in surgical time has been found (P 0.16). P  > 0.05 for seroma, neuroma, Frey syndrome, and facial palsy between different type of surgery. Frey syndrome in PSP: 6/135 (4.4%) in 2004 to 2012 and 2/219 (0.9%) in 2013 to 2020. The reduction between periods is significant (P < 0.04). Recurrence: 0.8% (3/354) for PSP patients, 3.4% (5/ 136) in enucleation and 10% (5/50) in ECD (P = 0.02). Partial superficial parotidectomy can be considered a minimally invasive and quick procedure with low complication rate. Our data seem to support this statement (large case series and long-term follow-up).

Programmed Cell Death-Ligand 1 in Head and Neck Squamous Cell Carcinoma: Molecular Insights, Preclinical and Clinical Data, and Therapies.

Aberrant expression of the programmed cell death protein ligand 1 (PD-L1) constitutes one of the main immune evasion mechanisms of cancer cells. The approval of drugs against the PD-1-PD-L1 axis has given new impetus to the chemo-therapy of many malignancies. We performed a literature review from 1992 to August 2022, summarizing evidence regarding molecular structures, physiological and pathological roles, mechanisms of PD-L1 overexpression, and immunotherapy evasion. Furthermore, we summarized the studies concerning head and neck squamous cell carcinomas (HNSCC) immunotherapy and the prospects for improving the associated outcomes, such as identifying treatment response biomarkers, new pharmacological combinations, and new molecules. PD-L1 overexpression can occur via four mechanisms: genetic modifications; inflammatory signaling; oncogenic pathways; microRNA or protein-level regulation. Four molecular mechanisms of resistance to immunotherapy have been identified: tumor cell adaptation; changes in T-cell function or proliferation; alterations of the tumor microenvironment; alternative immunological checkpoints. Immunotherapy was indeed shown to be superior to traditional chemotherapy in locally advanced/recurrent/metastatic HNSCC treatments.

Exploring Mitochondrial Localization of SARS-CoV-2 RNA by Padlock Assay: A Pilot Study in Human Placenta.

The ongoing COVID-19 pandemic dictated new priorities in biomedicine research. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, is a single-stranded positive-sense RNA virus. In this pilot study, we optimized our padlock assay to visualize genomic and subgenomic regions using formalin-fixed paraffin-embedded placental samples obtained from a confirmed case of COVID-19. SARS-CoV-2 RNA was localized in trophoblastic cells. We also checked the presence of the virion by immunolocalization of its glycoprotein spike. In addition, we imaged mitochondria of placental villi keeping in mind that the mitochondrion has been suggested as a potential residence of the SARS-CoV-2 genome. We observed a substantial overlapping of SARS-CoV-2 RNA and mitochondria in trophoblastic cells. This intriguing linkage correlated with an aberrant mitochondrial network. Overall, to the best of our knowledge, this is the first study that provides evidence of colocalization of the SARS-CoV-2 genome and mitochondria in SARS-CoV-2 infected tissue. These findings also support the notion that SARS-CoV-2 infection can reprogram mitochondrial activity in the highly specialized maternal-fetal interface.