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Background: Fatigue with reduced tolerance to exercise is a common persistent long-lasting feature amongst COVID-19 survivors. The assessment of muscle function in this category of patients is often neglected.Aim.: To evaluate the potential impact of a daily supplementation based on amino acids, minerals, vi-tamins, and plant extracts (Apportal (R)) on muscle function, body composition, laboratory parameters and self-rated health in a small group of COVID-19 survivors affected by fatigue.Methods: Thirty participants were enrolled among patients affected by physical fatigue during or after acute COVID-19 and admitted to the post-COVID-19 outpatient service at Fondazione Policlinico Gemelli in Rome between 1st March 2021 and 30th April 2021. All participants were evaluated at first visit (t0) and at control visit (t1), after taking a daily sachet of Apportal (R) for 28 days. Muscle function was analyzed using hand grip strength test, exhaustion strength time and the number of repetitions at one -minute chair stand test. Body composition was assessed with bioelectrical impedance analysis (BIA). Laboratory parameters, including standard blood biochemistry and ferritin levels, were evaluated at the first visit and during the control visit. A quick evaluation of self-rated health, before COVID-19, at t0 and t1, was obtained through a visual analogue scale (VAS). Results: Participants aged 60 years and older were 13 (43%). Females represented the 70% of the study sample. Participants hospitalized for COVID-19 with low -flow oxygen supplementation represented the 43.3% of the study sample while 3.3% received noninvasive ventilation (NIV) or invasive ventilation. Hand grip strength improved from 26.3 Kg to 28.9 Kg (p < 0.05) at t1 as compared to t0. The mean time of strength exhaustion increased from 31.7 s (sec) at t0 to 47.5 s at t1 (p < 0.05). Participants performed a higher number of repetitions (28.3 vs. 22.0; p < 0.05) during the one-minute chair stand test at

Diagnosis and management of sinonasal complications of dental diseases or treatment (SCDDT) may be challenging. We aimed to report our real-life experience in patients treated with endoscopic endonasal approach describing data about symptoms, etiology, extension of the disease and success rate. We evaluated retrospectively data about 262 patients diagnosed as SCDDT and managed from August 2015 to May 2022. In 44.65% cases, maxillary sinus complications were determined by a dental disorder; the remaining 55.34% of cases were iatrogenic. Patients were managed according to our multidisciplinary protocol including ENT, dental, and radiological evaluation. Treatments were planned with a personalized approach, based on the patient’s clinical characteristics; all patients were treated with an endonasal endoscopic mini-invasive conservative approach. Combined dental treatment was performed simultaneously in 152/262 (58%) of patients; in the remaining cases, it was postponed after surgery. The overall treatment success rate (symptom resolution and endoscopically observed maxillary sinus healing) was 96.5%. At 15 days after surgery, we observed a significant improvement in the quality of life. The mean post-operative Sinonasal outcome test-22 (SNOT-22) score was significantly lower compared to baseline (6 versus 43.4; p < 0.05). Our study showed that endoscopic sinus surgery can be a successful procedure for treatment of SCDDT, leading to fast resolution of sinonasal symptoms and improving the quality of life. Furthermore, the technique allows removal of migrated dental material or dental implants even in challenging cases.

The aim of the study was to evaluate survival in patients with advanced glottic laryngeal squamous cell carcinoma treated by bioradiotherapy (BioRT) with cetuximab and eventual salvage surgery (group A, n = 66) or upfront surgery (total laryngectomy or near-total laryngectomy) with or without postoperative radiotherapy (PORT) (group B, n = 66). The predictive role of HER1 expression in the bioselection of tumors was evaluated. Relapse-free (RFS), metastasis-free (MFS), overall (OS) survivals, salvageability, and rates of larynx preservation were analyzed. The two groups were balanced by propensity score method on their baseline characteristics. No significant differences in RFS and OS were found, while MFS results were significantly higher in group A (p = 0.04). Group A showed a 22% reduction in the probability of nodal metastasis (p = 0.0023), mostly in tumors with higher HER1 expression. The salvageability with TL at 3 years was 54% after prior BioRT and 18% after prior upfront NTL (p < 0.05). BioRT with cetuximab showed a reduction in the risk of lymph node relapse, particularly in the case of HER1 positive tumors, and it allowed to achieve a higher rate of functional larynx preservation and a higher salvageability compared with upfront surgery. HER1 analysis could be clinically useful in the bioselection of tumors that may benefit from BioRT with cetuximab, particularly in those with neck node metastatic propensity.

(1) Background: Periorificial face cancer (PFC), defined as both squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) arising around the eyelids, the nose vestibule and the lips, has very high incidence rates worldwide. The aim of our retrospective analysis, focusing on local control (LC) and patients’ degree of satisfaction with the cosmetic outcome, is to present the results of a single institutional series of patients affected by PFC and treated by interventional radiotherapy (brachytherapy–IRT). (2) Methods: We retrospectively evaluated patients affected by PFC who were treated at our Interventional Oncology Center (IOC) with interstitial IRT from 2012 to 2021 with doses and volumes specific for each subsite considered. (3) Results: We report the results of 40 patients affected by PFC and treated by HDR interstitial IRT. The median follow-up was 24 months. The actuarial 3-year LC was 94%. Regarding patients’ satisfaction, we found that 93% of patients were satisfied and only 7% of patients were not completely satisfied with the final cosmetic result. (4) Conclusions: Interstitial HDR IRT could be an effective therapeutic option providing adequate disease control and preventing potentially disfiguring surgical approaches. More numerous and standardized studies are warranted to confirm the available evidence.

Background: Fatigue with reduced tolerance to exercise is a common persistent long-lasting feature amongst COVID-19 survivors. The assessment of muscle function in this category of patients is often neglected. Aim.: To evaluate the potential impact of a daily supplementation based on amino acids, minerals, vi- tamins, and plant extracts (Apportal®) on muscle function, body composition, laboratory parameters and self-rated health in a small group of COVID-19 survivors affected by fatigue. Methods: Thirty participants were enrolled among patients affected by physical fatigue during or after acute COVID-19 and admitted to the post-COVID-19 outpatient service at Fondazione Policlinico Gemelli in Rome between 1st March 2021 and 30th April 2021. All participants were evaluated at first visit (t0) and at control visit (t1), after taking a daily sachet of Apportal® for 28 days. Muscle function was analyzed using hand grip strength test, exhaustion strength time and the number of repetitions at one- minute chair stand test. Body composition was assessed with bioelectrical impedance analysis (BIA). Laboratory parameters, including standard blood biochemistry and ferritin levels, were evaluated at the first visit and during the control visit. A quick evaluation of self-rated health, before COVID-19, at t0 and t1, was obtained through a visual analogue scale (VAS). Results: Participants aged 60 years and older were 13 (43%). Females represented the 70% of the study sample. Participants hospitalized for COVID-19 with low-flow oxygen supplementation represented the 43.3% of the study sample while 3.3% received noninvasive ventilation (NIV) or invasive ventilation. Hand grip strength improved from 26.3 Kg to 28.9 Kg (p < 0.05) at t1 as compared to t0. The mean time of strength exhaustion increased from 31.7 s (sec) at t0 to 47.5 s at t1 (p < 0.05). Participants performed a higher number of repetitions (28.3 vs. 22.0; p < 0.05) during the one-minute chair stand test at t1

Background: In order to evaluate the efficacy of intranasal mometasone furoate in patients with non-allergic rhinitis (NAR), a real-life, observational, prospective study is performed. Methods: Thirty-one patients (age 18-64 years) receive intranasal (mometasone furoate, 200 mu g b.i.d. for 15 consecutive days per month for 6 consecutive months), plus isotonic nasal saline. The cytologic pattern of local inflammation, nasal airflow, through peak nasal inspiratory flow (PNIF), quality of life (QoL), through the rhinitis quality of life questionnaire (RQLQ), the sinonasal outcome test (SNOT-22), the short-form 36-item health survey (SF-36v2), and the combined symptom medication score (CSMS), and, finally, olfactory function, through Sniffin' sticks-16 identification test (SSIT-16), are evaluated at baseline and after treatment. Results: NARNE is the most frequent cytological pattern (48% of the total sample). The therapeutic response shows improvement in olfactory function and QoL. Conclusions: The results of this study confirm that intranasal mometasone furoate is an effective treatment for patients with NAR.

The role of elective neck dissection during salvage surgery in patients with a clinically negative neck (cN0) is still discussed. The main objective of this work was to estimate the prevalence and predictive factors of occult neck nodes metastasis; we therefore aimed to evaluate the survival rate and the main oncologic outcomes of cN0 patients who underwent salvage total laryngectomy and elective bilateral neck dissection. In this retrospective observational study, we enrolled 80 cN0 patients affected by recurrent laryngeal cancer and who underwent salvage total laryngectomy and bilateral selective elective neck dissection. Several parameters were collected in order to find prognostic factors; finally, postoperative complications were reviewed and survival analysis was performed. Occult lymph node metastases were reported in 18 out of 80 patients (22.5%). Significant statistical correlation between lymphovascular invasion (p = 0.007), perineural invasion (p = 0.025) and occult nodal metastasis was found. Other variables (glottic subsite of recurrence, clinical T, pathological T, previous chemotherapy) were not significantly predictive of occult nodal metastasis. The 5-year OS, DSS, and RFS were 50.4%, 64.7%, and 63.4%, respectively. In conclusion, our single-institution data on a large cohort of patients, suggest performing routinely elective selective bilateral neck dissection during salvage total laryngectomy in cN0 patients due to the biological attitude of the tumor to spread to cervical nodes, considering an acceptable complications rate.

Eosinophilic otitis media (EOM) is a difficult-to-treat otitis media characterized by eosinophilic accumulation in the middle ear mucosa and effusion. It is resistant to conventional treatments and strongly associated with asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). The aim of our study is to evaluate the effectiveness of biologics drugs in the control of EOM. This is a retrospective no-profit real-life observational study, involving patients affected by refractory EOM and in treatment with different biologics for concomitant severe eosinophilic asthma or severe uncontrolled CRSwNP (Dupilumab: n = 5; Omalizumab: n = 1; Mepolizumab: n = 1; Benralizumab: n = 1). We analyzed data at baseline and at the 6-month follow-up, including specific nasal and otological parameters. We observed an improvement of all nasal outcomes, including NPS, SNOT-22, VAS, and smell function. Regarding specific otological parameters, we observed a significant reduction in the mean value of COMOT-15 score and of Otitis Severity Score at 6-month follow-up compared to baseline (p < 0.05). Finally, we observed an improvement in terms of air conduction hearing levels during the treatment. Our results demonstrated that anti type-2 inflammatory pathway biologics can be effective in improving symptoms control and in reducing the severity of eosinophilic otitis media when treating coexisting type-2 diseases, such as asthma and or CRSwNP.

Objectives: To confirm the data reported in our previous studies on the analysis of the variability of the electroglottographic signal in the pathological voice; to evaluate possible differences in variability between organic and functional pathologies; to identify any distinctive/typical EGG patterns for these pathologies. Methods: One hundred twenty-five subjects were enrolled (36 euphonic and 89 pathological: 24 functional dysphonia, 21 bilateral vocal nodules, 23 unilateral polyps and 21 unilateral cysts). All subjects were studied with videolaryngostroboscopy, spectrographic analysis of voice and electroglottography (EGG). The EGG signal variability was then investigated using amplitude-speed combined analysis, by means of a proprietary software algorithm. Amplitude and Speed variation were expressed as a new parameter, the Variability Index (VI), calculated both for the whole EGG signal recorded (VI-tot) and in each phase of the glottic cycle (VI-Q, absolute value; VI-Q%, percentage value). Results: In the comparison of VI values between pathological and normal groups, VI-tot and VI-Q2% (which corresponds to the final phase of vocal fold contact) were significantly greater in pathological subjects (P= 0.002). The comparison of VI values among subgroups of the various pathologies showed a difference for VI-tot (P< 0.0001) and VI-Q2% (P= 0.001); this difference was more marked in the cysts than in the functional dysphonia. The cut-off values of VI-tot and VI-Q2% were 0.191 and 18.17%, respectively (sensitivity and specificity 65.2% and 66.7% for VI-tot and 84.3% and 77.8% for VI-Q2%). Conclusions: The variability of the EGG signal investigated through the combined analysis of the amplitude and the speed of vibration using a proprietary algorithm software has proved useful not only to distinguish the normal voice from the pathological voice, but also to characterize which phases are more altered in the various voice pathologies studied, both functional and org

The cross-talk between oxidative stress and inflammation seems to play a key role in noise-induced hearing loss. Several studies have addressed the role of PPAR receptors in mediating antioxidant and anti-inflammatory effects and, although its protective activity has been demonstrated in several tissues, less is known about how PPARs could be involved in cochlear dysfunction induced by noise exposure. In this study, we used an in vivo model of noise-induced hearing loss to investigate how oxidative stress and inflammation participate in cochlear dysfunction through PPAR signaling pathways. Specifically, we found a progressive decrease in PPAR expression in the cochlea after acoustic trauma, paralleled by an increase in oxidative stress and inflammation. By comparing an antioxidant (Q-ter) and an anti-inflammatory (Anakinra) treatment, we demonstrated that oxidative stress is the primary element of damage in noise-induced cochlear injury and that increased inflammation can be considered a consequence of PPAR down-regulation induced by ROS production. Indeed, by decreasing oxidative stress, PPARs returned to control values, reactivating the negative control on inflammation in a feedback loop.

Objectives: The primary end point of this study was to evaluate the impact of bile acids on severity of laryngo-pharyngeal reflux (LPR) and the possible correlation with esophagitis and upper airway malignancies. The second end point was to evaluate if salivary bile acids and molecules other than pepsin might serve as diagnostic biomarkers of LPR. Design: Observational prospective comparative study. Setting: Otorhinolaryngology unit of a tertiary hospital. Participants: Sixty-two consecutive adult outpatients suspected of LPR. Main outcome measures: Bile acids, bilirubin and pepsinogen I-II were measured in saliva. Patients underwent pH metry and based on the results of bile acids were subdivided as acid, mixed and alkaline LPR. Results: Significantly higher Reflux Findings Score (RFS) and Reflux Symptoms Index (RSI) were seen in patients with alkaline and mixed LPR compared to acid LPR. Salivary bile acids >1 µmol/L seem to be a reliable indicator of the severity of LPR. Compared to those without, patients with esophagitis or a history of upper airway malignancy have high concentrations of bile acids in saliva. Among the molecules studied, bile acids were the most suitable for diagnosis of LPR, with a sensitivity of 86% and a positive predictive value of 80.7%. Conclusions: Our data suggest that high concentrations of bile acids are associated with higher values of RSI and RFS in LPR as well as a higher risk of esophagitis and history of upper airway malignancies. We finally observed that bile acids provided the best biometric parameters for diagnosis of LPR among the molecules tested.

Introduction: The novel coronavirus SARS-Cov-2 can infect the respiratory tract causing a spectrum of disease varying from mild to fatal pneumonia, and known as COVID-19. Ongoing clinical research is assessing the potential for long-term respiratory sequelae in these patients. We assessed the respiratory function in a cohort of patients after recovering from SARS-Cov-2 infection, stratified according to PaO2/FiO2 (p/F) values. Method: Approximately one month after hospital discharge, 86 COVID-19 patients underwent physical examination, arterial blood gas (ABG) analysis, pulmonary function tests (PFTs), and six-minute walk test (6MWT). Patients were also asked to quantify the severity of dyspnoea and cough before, during, and after hospitalization using a visual analogic scale (VAS). Seventy-six subjects with ABG during hospitalization were stratified in three groups according to their worst p/F values: above 300 (n = 38), between 200 and 300 (n = 30) and below 200 (n = 20). Results: On PFTs, lung volumes were overall preserved yet, mean percent predicted residual volume was slightly reduced (74.8 ± 18.1%). Percent predicted diffusing capacity for carbon monoxide (DLCO) was also mildly reduced (77.2 ± 16.5%). Patients reported residual breathlessness at the time of the visit (VAS 19.8, p < 0.001). Patients with p/F below 200 during hospitalization had lower percent predicted forced vital capacity (p = 0.005), lower percent predicted total lung capacity (p = 0.012), lower DLCO (p < 0.001) and shorter 6MWT distance (p = 0.004) than patients with higher p/F. Conclusion: Approximately one month after hospital discharge, patients with COVID-19 can have residual respiratory impairment, including lower exercise tolerance. The extent of this impairment seems to correlate with the severity of respiratory failure during hospitalization.

Objectives: Tinnitus is a common symptom largely impactful on quality of life, especially in the elderly. Our aim was to evaluate the efficacy of self-administered screening tests to correlate the severity of subjective perception of tinnitus with emotional disorders and the overall cognitive status. Methods: Patients aged ≥ 55 years with chronic tinnitus were recruited and submitted to a complete audiological evaluation; Tinnitus Handicap inventory (THI); Hospital Anxiety and Depression Scale (HADS-A and HADS-D) and Mini-Mental State Examination (MMSE). Demographic and audiological features of patients with and without cognitive impairment (MMSE score cut-off of 24/30) were analyzed in order to reveal the relationship among tinnitus, emotional disorders, and cognitive dysfunction. Results: 102 patients were recruited (mean age: 70.4 ± 9.6). THI score was directly related to HADS-A score (r =.63) HADS-D score (r =.66), whereas there was no relationship between tinnitus severity and MMSE (r =.13). CI and n-CI groups did not differ in the characteristics of tinnitus (p >.05), however, hearing threshold (p =.049) and anxious depressive traits measured with HADS-A (p =.044) and HADS-D (p =.016) were significantly higher in the group with cognitive impairment. Furthermore, age ≥ 75 years (p =.002, OR = 13.8), female sex (p =.032; OR = 6.5), severe hearing loss (p =.036; OR = 2.3), and anxiety (p =.029; OR = 9.2) resulted risk factors for CI. Therefore, in CI group MMSE score was inversely related to age (r = −.84). Conclusions: Cognitive impairment and psychiatric discomfort should be considered in tinnitus patients, related to increasing age, female sex, and severe hearing loss. Thus, self-administered questionnaires can be useful in addressing clinical approach.

Background: Compared to the other members of human epidermal growth factor family receptors (HER), the role of HER3 has not been well defined in laryngeal cancer. The predictive and prognostic role of HER3 has been the focus of clinical attention but the research findings are contradictory, especially in laryngeal squamous cell carcinoma (LSCC). The variable localization of HER3 within cancer cells and the role of HER3 in primary and acquired resistance to HER1-targeted therapies remain unclear. Methods: We performed a retrospective analysis of two cohorts of 66 homogeneous consecutive untreated primary advanced LSCC patients, in which co-expression of HER1, HER2 and HER3 receptors was investigated by semi-quantitative immunohistochemistry. The association of their pattern of expression with survival was evaluated by Kaplan–Meier and Cox’s proportional hazard analyses. Multivariable Cox proportional hazards models were developed to predict median 2- and 3-year RFS and 2.5- and 5-year OS. The Akaike information criterion technique and backwards stepwise procedure were used for model selections. The performance of the final Cox models was assessed with respect to calibration and discrimination. Results: Immunohistochemical labeling for HER1 and HER2 was localized both in the cell membrane and in the cytoplasm, while HER3 labeling was observed both in the cell cytoplasm and in the nucleus. HER3 expression was inversely correlated with HER1 positivity. The expression patterns of HERs were associated with tumor differentiation. In both cohorts of patients, HER1 expression was associated with reduced relapse-free (RFS) and overall survival (OS). In HER1 positive tumors, the co-expression with nuclear HER3 was associated with better RFS and OS, compared with HER3 negative tumors or tumors expressing HER3 at cytoplasmic level. HER3 expressing tumors had a higher Geminin/MCM7 ratio than HER3 negative ones, regardless of HER1 co-expression. Multivariable analyses identified a

PMID: 33427617 Abstract Objectives: Rheumatoid arthritis (RA) may affect the postural control through abnormal sensory inputs and impaired motor responses. Sensory Organization Test (SOT) objectively evaluates contribution of different sensorial afferences in postural control. The aim of the study is to assess mechanisms of postural instability and their relations with disability and disease characteristics in an early RA(ERA) cohort. Methods: The equilibrium scores were assessed in 30 ERA patients and 30 age- and sex-matched controls. The somatosensory (SOM), visual (VIS) and vestibular (VEST) ratios were computed to assess the use of different sensory and the composite equilibrium score (CES) as a measure of global balance performance. Results: ERA patients had lower CES (78.4±6.0% vs. 83.4±5.0%, p=0.002), SOM ratio (98.5±1.8% vs. 99.6±2.1%, p=0.035), VIS ratio (85.2±7.6% vs. 91.5±6.0%, p=0.001) and VEST ratio (70.8±10.0% vs. 80.3±7.8%, p<0.001) compared to controls. The presence of ankle arthritis correlated negatively to both SOM (r=-0.369, p=0.045) and VIS ratio (r=0.470, p=0.009), pain severity to CES (r=-0.389, p=0.045) and VIS ratio (r=-0.385, p=0.048) and HAQ-DI to CES (r=-0.591, p=0.001), SOM (r=-0.510, p=0.004) and VIS ratio (r=-0.390, p=0.033.). Patients-reported postural instability was associated with lower CES (75.4±5.4% vs. 80.7±5.5%, p=0.016) and VEST ratios (66.5±10.1% vs. 74.1±8.8%, p=0.036). SOT outcomes did not differ according to acute phase reactants, disease activity or autoantibody positivity. Conclusions: RA patients showed an early impairment of postural control related to the degree of disability and subjective postural instability. Our data suggest that the lack of balance could result from both impaired motor response and abnormal sensory organisation.

There are controversial results about the role of “ex novo” HLA-DR expression by tumor cells and its correlation with the oncological outcomes. Unfortunately, little is known about HLA-DR expression in laryngeal cancer tumor cells. The main purpose of this retrospective study is to strengthen the usefulness of studying “ex novo” HLA-DR expression on tumor cells from primary laryngeal squamous cell carcinoma (LSCC) patients and investigate its correlation with clinical outcome. We analyzed HLA-DR expression by immunohistochemical analysis in 56 patients with LSCC. The “ex novo” HLA-DR expression on laryngeal cancer tumor cells, assessing non-neoplastic LSCC – adjacent tissue, and the association of HLA-DR expression (HLA-DR+) with clinical outcomes were investigated. HLA-DR+ tumor cells were detected in 18/56 LSCC patients (32.1%). All specimens of non-neoplastic laryngeal carcinoma-adjacent tissue resulted HLA-DR negative (HLA-DR-). A statistically significant association was observed between HLA-DR + and well differentiated tumors (G1) (p<0.001). The Kaplan-Meier method showed how HLA-DR+ is significantly associated with both a better disease specific survival (HLA-DR+=100% vs. HLA-DR-=77.4%; p=0.047) and a better relapse free survival (HLA-DR+=100% vs. HLA-DR-=72.3%; p=0.021). Cox regression univariate analysis for death of disease confirmed a higher HR for HLA-DR absence on the surface of epithelial tumor cell [HR:37.489; 95% CI:0.750-18730.776; p=0.253] and for high-grade (G3) tumors [HR:18.601; 95% CI:3.613-95.764; p<0.0001]. Our results confirm that MHC class II HLA-DR expression is activated in a sub-set of LSCC patients. Evaluation of HLA-DR expression in LSCC could be useful for prognosis and future approaches towards personalized therapy.

Cerebrospinal fluid (CSF) leak remains a rare condition, characterized by serious complications and potentially fatal. According to different etiologies, CSF leaks may be classi-fied into two main categories: traumatic and spontaneous. Spontaneous fistulas seem to be mainly related to obesity and idiopathic intracranial hypertension. Diagnosis is both clinical and radiological. During the last three decades, surgical treatment has mostly shifted to endonasal endoscopic approach, which widely demonstrated to be more effective than invasive intracranial ones. Post-operative complications, long-term sequelae and hospital stay are strongly reduced thanks to endoscopic approach. The diagnosis and treatment of CSF leaks represent a difficult and challenge task. The main effort seems to be related to the precise localization of the leak. An accurate assessment of both predisposing factors and comorbidities is mandatory in case of spontaneous leaks. However, a clinical multidiscipli-nary evaluation as well as treatment, is essential to decrease the rate of failure of surgery. The presence of a dedicated instruments, the Skull Base Team, the knowledge of recon-structive materials and techniques represents a decisive result in therapeutical management even if for each patient an effective therapeutic algorithm can be obtained considering the correct leak detection and characteristics. In conclusion the strict teamwork with neurosur-geons, neuroradiologists, ophtalmologists will enable the development also of innovative biomaterials, which could spread and standardize multi-layer techniques, nowadays still related to surgeon preferences.

[This corrects the article DOI: 10.1155/2020/2291759.].

Introduction: allergy may be an important risk factor for adenotonsillar disease in children, although conflicting results have been reported in the literature. In previous articles, authors often failed in distinguishing between adeno-tonsillar hypertrophy and recurrent tonsillitis and in not discriminating between isolated or combined adenoid and tonsillar hypertrophy. Aim: to evaluate clinical evidence and biomarkers linking allergy to different phenotypes of adeno-tonsillar disease. Furthermore, we questioned whether anti-allergy treatment might prevent occurrence of adeno-tonsillar disease or improve its specific management. Methods: our systematic review, in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) process, yielded 1010 articles finally screened. This resulted in 21 full texts that were included in a qualitative analysis. Results: literature data support the association between allergy and combined adeno-tonsillar hypertrophy and isolated adenoid hypertrophy, whereas describe a mainly negative correlation between allergy and isolated tonsillar hypertrophy. The results of this review suggest that local allergic inflammation may play a role in adeno-tonsillar hypertrophy. Data correlating bacterial recurrent tonsillitis and allergy are few, although evidence from the lab revealed that allergy might suppress innate immunity in tonsillar tissue by reducing levels of anti-microbial proteins. Conclusion: basing on our qualitative analyses allergy should not be misdiagnosed in children with combined adenotonsillar hypertrophy or isolated adenoid hypertrophy, whereas evidence do not support a link between allergy and isolated tonsil hypertrophy. Finally, some data support a link between allergy and recurrent adeno-tonsillar infection although future studies are required to confirm this data. We summarized our conclusions in a practical algorithm.

Background: Allergic rhinitis is a common childhood disease responsible for a major impact on quality of life and healthcare resources. Many hypotheses have been proposed to explain the link between allergy and otitis media, although a definitive mechanism has not been identified yet. One of the major critical points is that authors failed in distinguishing among different phenotypes of middle ear inflammation. This review pointed out literature evidence from the laboratory and clinical experience linking allergy to different phenotypes of otitis media in children. Methods: We performed a systematic review in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) process. Our search yielded 3010 articles that were finally screened. This resulted in 20 manuscripts of which the full texts were included in a qualitative analysis. We paid particular attention in distinguishing among phenotypes of otitis media. Results: Clinical evidence and analyses of biomarkers suggested that allergy may be linked to some phenotypes of otitis media and, in particular, to otitis media with effusion (OME) and acute re-exacerbations in children with middle ear effusion. It was not possible to perform the analysis for allergy and acute and chronic otitis media because of paucity and heterogeneity of data. Conclusion: Allergy should be considered in the diagnostic workup of children with OME as well as OME should be excluded in children with persistent moderate to severe AR. In these cases, clinicians should evaluate prompt and accurate treatment of allergy in improving outcomes, although futures studies are required to increase evidence supporting that anti-allergy treatment may be effective in the recovery and outcome of otitis media with effusion.

Purpose: Surgery, external beam radiotherapy (EBRT), and interventional radiotherapy (IRT, BrachyTherapy BT) are the current therapeutic options for nose vestibule (NV) squamous cell carcinoma (SCC). In this article, we evaluate the nose functional parameters of patients affected by SCCs of the NV, primarily treated by interstitial IRT comparing them with healthy controls and with patients treated with intensity-modulated EBRT. Methods: Ten patients treated by using IRT (group 1), 10 healthy controls and eight patients treated by EBRT (group 2) on the region of the nose were submitted to clinical evaluation (with the NOSE scale score), rhinomanometry, olfactory testing, nasal citology, and evaluation of mucociliary clearance through saccharine test. Results: No long-term skin or cartilaginous toxicity are recorded. The olfactometry threshold discrimination identification TDI is lower in EB group. The mean NOSE scale score was significantly higher in group 2 than in group 1 and healthy controls (p < 0.05). The distribution of cytologic patterns resulted significantly different as well. Patients treated by EB have a significantly impaired mucociliary clearance, with a mean time for the transport of the stained marker, which is more than double in the patients treated by EB than in those treated with IRT (p < 0.001). Conclusions: Nasal function and cytological findings are significantly better, substantially preserved, in patients treated by IRT than in those treated by EBRT, bringing new relevant evidence for the establishment of interstitial IRT as the new standard for the treatment of the primary lesion in cT1 and cT2 -Wang staging NV SCCs.

Purpose: The surgical thyroid disease includes upper aerodigestive complaints with not homogenous prevalence and specific features. The purpose was to analyze before and after total thyroidectomy (TT) the prevalence and severity of voice, swallowing, respiratory, and reflux airway symptoms in relation with thyroid weight. Methods: A total of 98 consenting patients undergoing TT were enrolled. Preoperatively, 1 and 3 months after TT, patients underwent videolaryngoscopy, subjective evaluation of voice (VIS), swallowing (SIS and EAT-10), respiratory (mMRC), and reflux symptoms (RSI, Gerd-Q). The scores were analyzed based on thyroid weight (<25 gr, 26–50 gr, 51–75 gr, >75 gr) and post-operative score gain was calculated from the score before TT and the follow-up examination. Results: In total, 40/98 selected cases of uncomplicated TT completed the postoperative evaluation. Endoscopic signs suggestive of reflux disease were observed in 1/40 (2.5%) and 0/19 cases before and after TT respectively. The prevalence of cases with abnormal reflux symptom index decreased significantly after surgery (8/40 vs 1/40) (p < 0.05), similarly occurred for the Gerd-Q (4/40 vs 1/40) (p < 0.05). Three months after TT the voice, swallowing and respiratory scores were significantly lower than the preoperative ones (p < 0.05). The SIS correlated positively with EAT-10 and RSI. After 3 months the postoperative score gain of voice, swallowing, respiratory, and reflux symptoms (Gerd-Q) was statistically higher (p < 0.05) in the cases with heaviest gland. Conclusions: The surgical thyroid disease is associated to mild aerodigestive preoperative compressive symptoms, that include respiratory abnormalities and reflux like symptoms, regardless of the gland weight. In absence of endoscopic signs of airway reflux the presence of reflux symptoms suggests an overlapping with thyroid neck complaints. The patients undergoing uncomplicated TT had improvement in compressive symptoms and

Objective: Periprosthetic leakage represents the most demanding long-term complication in the voice prosthesis rehabilitation. The aim of this article is to discuss the various causes of periprosthetic leakage and to propose a systematic management algorithm. Study Design: Retrospective cohort study. Setting: Otolaryngology clinic of the University Polyclinic A. Gemelli–IRCCS Foundation. Methods: The study included 115 patients with voice prosthesis who were treated from December 2014 to December 2019. All patients who experienced periprosthetic leakage were treated with the same step-by-step therapeutic approach until it was successful. Incidence, management, and success rate of every attempt are analyzed and discussed. Results: Periprosthetic leakage was reported 330 times by 82 patients in 1374 clinic accesses. Radiotherapy, timing of tracheoesophageal puncture, and type of total laryngectomy (primary or salvage) did not influence the incidence of periprosthetic leakage. Salvage total laryngectomy increases the risk of more clinically relevant leakages. Conclusion: By using a systematic algorithm with a step-by-step standardized approach, periprosthetic leakage management could become a less treacherous issue.

Objective: Fine needle aspiration cytology (FNAC) is a well-established diagnostic procedure for head and neck masses not clearly originating from mucosal or cutaneous surfaces. We analysed head and neck masses evaluated over a 2-year period, to assess the reliability of FNAC for the evaluation of malignancy. Methods: We enrolled all patients undergoing FNAC, from April 2013 to July 2015, in a single service of a large Italian university hospital. Relevant clinical data and ultrasonographic parameters of the lesions were recorded. We performed both conventional and thin-prep smears. Clinical presentation, ultrasonographic features and final cytology diagnoses were analysed and correlated with histology. Results: The series included 301 lesions in 285 patients, with a single (94.4%) or two (5.6%) lesions. Only eight samples were considered non-diagnostic/inadequate (2.6%). Among the cases, 139 FNAC (46.1%) underwent surgery. Cytological-histological correspondence was found in 89% of the cases. Concerning malignancy, we documented less than 4% false positives and less than 2.5% false negatives, with 92.7% sensitivity and 94.6% specificity. Conclusion: FNAC diagnosis can be highly specific. Most importantly, it is highly reliable in assessing malignancy, thus defining the priority and guiding the management procedures.

Purpose: Parastomal recurrence of squamous cell carcinoma (SCC) with tracheal involvement following salvage total laryngectomy after prior concurrent chemoradiotherapy is one of the most insidious challenges in head and neck surgery because a complex reconstruction is often required for covering a large area of skin loss, filling the dead space beneath, tracheal reconstruction and suspension, and tracheostome resurfacing. The aim is to describe our experience with the internal mammary artery perforator (IMAP) propeller flap for tracheal and tracheostome reconstruction and neck resurfacing after parastomal and cervical trachea resection, especially for suspension and anchoring the stump of the residual distal trachea to the island flap itself. Methods: We describe IMAP flap reconstruction after resection of parastomal recurrence of SCC requiring cervical trachea resection in five patients between January 1, 2005 and August 30, 2019. Results: IMAP propeller flap was successfully used for reconstruction after complex resection of parastomal recurrence of SCC with cervical trachea involvement in all cases. The mean length and width were, respectively, 16.8 cm (range 13–23) and 6.9 cm (range 5.5–8). We did not report complications of both the donor and the recipient site. Pharyngo-cutaneous or tracheoesophageal fistulas and wound dehiscence were not observed. Conclusions: to the best of our knowledge, this is the first report about the use of the IMAP propeller flap in this more complex clinical setting and we provide the message that this surgical procedure is worthy of consideration.

Dysphagia is common in tracheostomized patients who underwent head and neck surgery for cancer treatment. The objective of this study was to evaluate, by means of oropharyngoesophageal scintigraphy (OPES), the impact of an occluded tracheal tube (TT) on swallowing in patients treated for head and neck cancer before hospital discharge, to provide further information to the benefit of out-patient care management. From October 2018 to November 2019, we enrolled 19 tracheostomized patients (6 females and 13 males; mean age 61 years) who underwent primary surgical resection of head and neck tumor and swallowing rehabilitation during hospitalization. All subjects underwent a double-standard OPES, one with occluded tracheal tube and the other without TT, with their tracheal stoma being closed directly by a plaster. For each study, we assessed and compared the following quantitative parameters: oral transit time (OTTsec), pharyngeal transit time (PTTsec), esophageal transit time (ETTsec), oral retention index (ORI%), pharyngeal retention index (PRI%), esophageal retention index (ERI%), and aspiration percentage (AP%). The mean values of OTT, PTT, ORI%, PRI%, and ERI% were abnormal during OPES both with TT and without TT and did not statistically differ between the two tests (p > 0.05). Aspiration was detected in 4 cases out of 19 (21.05%) cases during OPES with TT and in 4/19 (21.05%) cases without TT who showed a mean AP% of 11.4% and 11.5% respectively (p > 0.05). Patients with abnormal AP% (> 0%) during OPES with TT showed aspiration signs without TT. Our study showed that the mere presence of a closed tracheal tube does not impact significantly the oropharyngeal transit of bolus during swallowing. This result suggests the possibility to maintain a small-diameter occluded tracheal tube in place for the postsurgical management of head and neck cancer patients.

In the original version of this Article, the author Anna Rita Fetoni was incorrectly indexed. This error has now been corrected.

Background. Pregnancy is a specific female physiological period characterized by significant changes, included oto-logical and neurotological manifestations. Vestibular disorders like vertigo and dizziness, are common complaints from pregnant women to primary care. Objectives. The aim of this paper is to describe clinical pictures, evaluation methods and therapeutic options of acute vertigo in pregnancy with the related pathogenetic hypotheses. Method. We describe 11 cases of vertigo in pregnancy. All patients underwent audio-vestibular evaluation, consisting of pure-tone audiometry, impedance and clinical testing of the vestibular function, the “bed side examination”. Results. Audiological evaluation showed normal pure-tone audiometry and impedance in 10 patients. Only in one case a sudden right total deafness was highlighted with vestibular areflexia, showing a secondary positional vertigo. Seven patients presented a benign paroxysmal positional vertigo (BPPV) effectively treated by liberatory maneuvers. Three patients had a diagnosis of vestibular neuritis and they were treated with corticosteroids therapy with a complete resolution of dizziness and vertigo in one month. Conclusions. Our results point out the importance of multidisciplinarity between otolaryngologist, neurologist and gynecologist. From a pathogenic point of view, the vascular etiology, strictly related to the gravidic hormonal variations, is often hypothesized.

Background: It is well known that age-related hearing loss (ARHL) is strongly associated with dementia. Different hypotheses have been considered to explain this link, including sensorial deprivation, the reduction in cognitive reserve, and the presence of shared pathological pathways (microvascular damage of the brain). Aims: We carried out a study of the audiological and neuropsychological characteristics of a sample of hearing impaired but cognitively healthy individuals (HIH). The aim of our study was to carefully outline the neuropsychological profile of the patients in order to verify whether hearing loss correlated with deficits in specific cognitive domains. Results: Episodic memory is affected by the presence of hearing loss, while semantic competences, syntactic, and grammar skills seem not to be affected. Furthermore, some audiological features linked to the intelligibility of spoken words can predict the presence of executive dysfunction; the same does not apply to memory impairment. Conclusion: In HIH, executive functions are widely employed in maintaining an acceptable level of comprehension of spoken language; consequently, other cognitive domains and instrumental abilities in HIH are not properly supported. Thus, it is arguable that programs of hearing rehabilitation for HIH could restore the allocation of attentional resources to the functioning of other cognitive domains.

Introduction. Serum amino acid (AA) profiles represent a valuable tool in the metabolic assessment of cancer patients; still, information on the AA pattern in head and neck cancer (HNC) patients is insufficient. The aim of the study was to assess whether serum AA levels were associated with the stage of neoplastic disease and prognosis in primary HNC patients. Methods. Two hundred and two primary HNC patients were included in the study. Thirty-one AAs and derivatives were measured in serum through an ultraperformance liquid chromatography-mass spectrometry (UPLC-MS). The association between AA concentrations and the stage (advanced versus early) of HNC was estimated using a multivariable logistic regression model. A multivariable Cox regression model was used to evaluate the prognostic significance of each AA. Results. At the multivariable logistic regression analysis, increased levels of alpha-aminobutyric acid, aminoadipic acid, histidine, proline, and tryptophan were associated with a reduced risk of advanced stage HNC, while high levels of beta-alanine, beta-aminobutyric acid, ethanolamine, glycine, isoleucine, 4-hydroxyproline, and phenylalanine were associated with an increased risk of advanced stage HNC. Furthermore, at multivariate analysis, increased levels of alpha-aminobutyric acid were associated with increased overall survival (OS), while high levels of arginine, ethanolamine, glycine, histidine, isoleucine, 4-hydroxyproline, leucine, lysine, 3-methylhistidine, phenylalanine, and serine were associated with decreased OS. Conclusions. Our study suggests that AA levels are associated with the stage of disease and prognosis in patients with HNC. More study is necessary to evaluate if serum AA levels may be considered a hallmark of HNC and prove to be clinically useful markers of disease status and prognosis in HNC patients.

The expression of potential stem cell markers in HNSCCs was investigated to assess their potential clinical role. 69 primary, previously untreated oral (OSCC) and oropharyngeal squamous cell carcinomas (OPSCC) were enrolled; personal, clinical and follow-up data were collected. HPV infection and expression of 5 potential stem cell markers (CD44, CD133, Oct-4, Nanog, and Sox-2) were evaluated. HPV+ OPSCC showed lower expression of Nanog. The cytoplasmic expression of Nanog was associated with significantly worse prognosis in OPSCC, but not in OSCC. Sox-2 staining was more intense among OPSCCs. Sox-2 nuclear staining was associated with worse prognosis. Nanog expression was associated with HPV-OPSCC and may have a role as a surrogate diagnostic marker. In general, the expression profile of some stem cell markers in HNSCC seems to vary according to the site of origin and HPV infection. Nanog and Sox-2 may also have prognostic value.

Purpose of the Review: We provide a systematic review of experimental and clinical evidences linking allergy to acute, including common cold, and chronic rhinosinusitis in children. Furthermore, we questioned if anti-allergy treatment may prevent the occurrence of rhinosinusitis or improve outcomes of its specific management. Recent Findings: Allergic rhinitis is a common childhood disease in industrialized countries that is responsible for a major impact on quality of life and healthcare resources. Over the years many authors tried to correlate allergy with comorbidities and in particular to the onset of rhinosinusitis including common cold, even though conflicting results are frequently reached. We performed a systematic review in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) process. Our search yielded 7103 that were finally screened. This resulted in 25 publications of which the full texts were assessed and included in a qualitative analysis per different phenotypes of rhinosinusitis. Summary: The evidence suggests that allergy may lead to overall impairment of mechanical and immunological defense function of the nasal mucosa against viruses and that anti-allergy treatment may significantly decrease the number and severity of upper respiratory tract infections including common colds in children. It was not possible to perform the analysis for allergy and post-viral acute rhinosinusitis, bacterial acute rhinosinusitis, and recurrent acute rhinosinusitis because of paucity and heterogeneity of data. Although there is no definitive proof of causation linking allergy to chronic rhinosinusitis, studies lead to suppose that anti-allergy treatment may improve outcomes of specific CRS treatments.

Introduction: For the EARs NOSE AND THROAT (ENT) surgeon, there are many challenges that show-up in the clinical management of a patient affected by a head and neck cancer during COVID-19 pandemic, especially in the postoperative period. Methods: During the acute COVID-19 emergency phase in Italy, we analyzed the management of a patient affected by a head and neck cancer. We reported several clinical data about the hospitalization period, pointing out the difficulties encountered both from clinical and management point of view. Results: During pandemic, we admitted 27 oncological patients at our ENT Department. Delays in surgical procedures, complications of hospitalizations, need for radiological studies, and possible transfer to other hospital ward, due to suspect SARS-CoV-2 infection, were registered. Conclusions: The changes in the whole health care system during the COVID-19 pandemic have impacted the management of patients with head and neck cancer, generating several clinical challenges for the ENT surgeon.

Management of late complications represents the main reason for reluctance in using voice prosthesis rehabilitation. The aim of this paper is to report our experience by describing the one-year management of a large cohort of patients in order to clarify how demanding management is in terms of burden on clinicians. Between June 2017 and June 2018, each access made at the Otolaryngology Clinic of our Institute for issues related to prosthesis by 70 laryngectomised patients rehabilitated by voice prosthesis was registered in a specific database. A review of the data provided information on the incidence, management and outcomes of adverse events encountered during the selected time frame. In addition, a T test was used to evaluate the differences between irradiated and non-irradiated patients and between primary and secondary tracheo-oesophageal-puncture. Leakage through the prosthesis was the most common cause for access (51.86%). The median number of accesses per patient per year was 3.47. The speech therapist autonomously managed 18.1% of accesses. The median number of accesses per patient per year needing a physician was 2.84. The median lifetime of the prosthesis was 4.85 months. Radiotherapy or modality (primary or secondary) of the puncture did not influence the number of accesses per year or the prosthesis lifetime. This retrospective analysis of results highlighted the most frequent issues and the most effective measures to deal with them, which allowed us to define a systematic algorithm to standardise and ease long-term outpatient management.

Purpose: The aim of this paper was to evaluate treatment outcomes following interventional radiotherapy (brachytherapy – BT) for nasal vestibule cancer. Material and methods: Considering histological diagnosis and staging, a multidisciplinary tumor board indicated an exclusive interventional radiotherapy for all patients. Plastic tubes were placed mainly with interstitial approach. The total dose was 44 Gy in 14 fractions, 3 Gy/fraction (except for the first and last fractions, 4 Gy), 2 fractions per day (b.i.d.), 5 days a week. Inclusion criteria for this analysis were: patients affected by squamous cell carcinoma with follow-up more than 6 months. Results: 20 patients with primary nasal vestibule cancer were treated with IRT from May 2012 to June 2019. We excluded 4 patients due to follow-up less than 6 months and 2 patients affected by basal cell carcinoma. In total, 14 consecutive previously untreated patients were considered for definitive analysis, median age was 67.5 (range, 51-83) years, median follow-up was 53 (range, 6-84) months. All patients followed the protocol except one, who received a total dose of 42 Gy in 12 fractions, 3 Gy per 6 fractions, and 4 Gy per 6 fractions. Local control at 12, 24, and 36 months was 85.7%. Overall survival at 12 months was 92.3%, at 24 months was 76.9%, and at 36 months was 69.2%. Staging system proposed by Wang was statistically significant on local control (LC), disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS). Excellent cosmetic results were observed. Conclusions: This study confirms that interventional radiotherapy could be considered as a definitive treatment in nasal vestibule cancer with excellent oncological and cosmetic outcomes.

Jacopo Galli1, Maria Raffaella Marchese2, Claudia De Canio3, Mariachiara Mandiello3, Giuseppe Michele Mangone3, Angela Anna Padula4, Giuseppina Abignano4, Lorenzo Santandrea3, Gaetano Paludetti1 1 Department of Aging, Neuroscience, Orthopedics and Head and Neck Sciences, UOC of Otorhinolaryngology, Istituto di Otorinolaringoiatria “Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore”, Roma, Italy; 2 Department of Aging, Neuroscience, Orthopedics and Head and Neck Sciences, UOC of Otorhinolaryngology, “Fondazione Policlinico Universitario A. Gemelli IRCCS”, Roma, Italy; 3 ENT Department, San Carlo Hospital, Potenza, Italy; 4 Rheumatology Institute of Lucania (IReL) and Rheumatology Department of Lucania, San Carlo Hospital of Potenza and Madonna delle Grazie Hospital of Matera, Potenza, Italy.

Objectives: The aim of this systematic review was to estimate the osteoradionecrosis rate in patients with head and neck cancer due to teeth extraction performed before radiotherapy and to identify possible risk factors. Material and Methods: PRISMA protocol was used to evaluate and present the results. PubMed, Scopus and Web of Science were used as search engines: English full-length papers of clinical studies, in peer-reviewed journals, were investigated. Cumulative meta-analysis was performed with a random effects model (PROSPERO registration code: CRD42018079986). Results: Among 2,020 records screened, 8 were included in this review. Sixteen of 494 patients who underwent tooth extraction before radiotherapy developed osteoradionecrosis, with an osteoradionecrosis incidence of 2.2% (95% Confidence of Interval = 0.6–3.9, p <.185, I2 = 3,044%). All cases were reported in the mandible. No other clinical risk factor for osteoradionecrosis was detected. Conclusions: Even if it is generally recommended to remove oral foci before radiotherapy, this systematic review confirmed that teeth extractions before radiotherapy represent a risk factor for osteoradionecrosis; the considerable amount of missing data prevented us from identifying other possible risk factors for osteoradionecrosis onset. Major efforts should be done to perform sounder methodological clinical investigations.

For survivors of severe COVID-19 disease, having defeated the virus is just the beginning of an uncharted recovery path. What follows after the acute phase of SARS-CoV-2 infection depends on the extension and severity of viral attacks in different cell types and organs. Despite the ridiculously large number of papers that have flooded scientific journals and preprint-hosting websites, a clear clinical picture of COVID-19 aftermath is vague at best. Without larger prospective observational studies that are only now being started, clinicians can retrieve information just from case reports and or small studies. This is the time to understand how COVID-19 goes forward and what consequences survivors may expect to experience. To this aim, a multidisciplinary post-acute care service involving several specialists has been established at the Fondazione Policlinico Universitario A. Gemelli IRCSS (Rome, Italy). Although COVID-19 is an infectious disease primarily affecting the lung, its multi-organ involvement requires an interdisciplinary approach encompassing virtually all branches of internal medicine and geriatrics. In particular, during the post-acute phase, the geriatrician may serve as the case manager of a multidisciplinary team. The aim of this article is to describe the importance of the interdisciplinary approach––coordinated by geriatrician––to cope the potential post-acute care needs of recovered COVID-19 patients.

Objective: The authors have evaluated their experience in pre-operative direct puncture embolization of hypervascular tumors of the head and neck using SQUID 12, an embolic liquid agent. Methods: Between July 2016 and March 2019, the authors retrospectively reviewed clinical, embolization and surgical data of 11 consecutive patients with 12 hypervascular head and neck tumors who had undergone pre-operative embolization using SQUID 12. Percutaneous embolizations were performed by inserting a 19-22 Gauge needle directly into the tumor under ultrasound, fluoroscopic and/or endoscopic guidance. The hub of the needle was connected to a 15-cm DMSO-compatible extension tube, and the SQUID 12 was injected. Results: Total or near-total devascularization was achieved in 11 over 12 cases. Complete en-bloc tumor removal by surgery was achieved in all cases. Only one patient required blood transfusion. No major periprocedural adverse events were recorded. Conclusions: Direct puncture embolization of hypervascular tumors of the head and neck using SQUID 12 seems to be safe and effective. It may offer almost complete devascularization due to homogenous, deep penetration in the tumor, with optimal visibility of the agent throughout the percutaneous procedure. It may reduce intraoperative blood loss and the need for transfusion, thus facilitating complete surgical resection.

Immunotherapy can be used for cutaneous, mucosal, uveal and conjunctival melanoma. Nevertheless, we cannot expect the same benefit from checkpoint inhibitors for all the types of melanoma. The different biological features can explain the variable efficacy. The main results obtained with immune checkpoint inhibitors in the various types of melanoma were reviewed.

For survivors of severe COVID-19 disease, having defeated the virus is just the beginning of an uncharted recovery path. What follows after the acute phase of SARS-CoV-2 infection depends on the extension and severity of viral attacks in different cell types and organs. Despite the ridiculously large number of papers that have flooded scientific journals and preprint-hosting websites, a clear clinical picture of COVID-19 aftermath is vague at best. Without larger prospective observational studies that are only now being started, clinicians can retrieve information just from case reports and or small studies. This is the time to understand how COVID-19 goes forward and what consequences survivors may expect to experience. To this aim, a multidisciplinary post-acute care service involving several specialists has been established at the Fondazione Policlinico Universitario A. Gemelli IRCSS (Rome, Italy). Although COVID-19 is an infectious disease primarily affecting the lung, its multi-organ involvement requires an interdisciplinary approach encompassing virtually all branches of internal medicine and geriatrics. In particular, during the post-acute phase, the geriatrician may serve as the case manager of a multidisciplinary team. The aim of this article is to describe the importance of the interdisciplinary approach––coordinated by geriatrician––to cope the potential post-acute care needs of recovered COVID-19 patients.

Objectives: The aim of this systematic review was to estimate the osteoradionecrosis rate in patients with head and neck cancer due to teeth extraction performed before radiotherapy and to identify possible risk factors. Material and Methods: PRISMA protocol was used to evaluate and present the results. PubMed, Scopus and Web of Science were used as search engines: English full-length papers of clinical studies, in peer-reviewed journals, were investigated. Cumulative meta-analysis was performed with a random effects model (PROSPERO registration code: CRD42018079986). Results: Among 2,020 records screened, 8 were included in this review. Sixteen of 494 patients who underwent tooth extraction before radiotherapy developed osteoradionecrosis, with an osteoradionecrosis incidence of 2.2% (95% Confidence of Interval = 0.6–3.9, p <.185, I2 = 3,044%). All cases were reported in the mandible. No other clinical risk factor for osteoradionecrosis was detected. Conclusions: Even if it is generally recommended to remove oral foci before radiotherapy, this systematic review confirmed that teeth extractions before radiotherapy represent a risk factor for osteoradionecrosis; the considerable amount of missing data prevented us from identifying other possible risk factors for osteoradionecrosis onset. Major efforts should be done to perform sounder methodological clinical investigations.

BACKGROUND: the primary end point of our study was to define risk factors and identify the underlying conditions that may have led to the abuse of vasoconstrictors in rhinitis medicamentosa. Moreover, we analysed factors that may influence the vasoconstrictors discontinuation. METHODOLOGY: this was a prospective case-control observational study. Cases and controls were evaluated at the baseline in order define factors that may have influenced onset of rhinitis medicamentosa. They were re-evaluated at 3 months to verify symptoms control and drug discontinuation. Finally, they underwent a phone call questionnaire after 12 months regarding drug discontinuation. A potential bias of our study is that evaluating discontinuation we included subjects treated differently according to the main diagnosis. RESULTS: patients with rhinitis medicamentosa were more frequently smokers than controls, they had higher mean HAMA scores and positive psychiatric diseases history. Additionally, we frequently detected a local inflammation at nasal cytology in patients with rhinitis medicamentosa. A significant improvement in all nasal symptoms scores was observed in cases and controls but 29.4% of cases did not discontinue the vasoconstrictors. Two major factors negatively influenced discontinuation: positive nasal cytology and pathological HAMA score. CONCLUSION: we observed that positive local inflammation, anxiety and smoking habit correlate positively with vasoconstrictors abuse. In addition, we demonstrated that anxiety and local inflammation were the most important factors impairing drug discontinuation.

PURPOSE: The objective of this study is to analyse the relationship between the endoscopic signs of laryngo-pharyngeal reflux, the lingual tonsil hypertrophy (LTH) and its inflammation, adopting Narrow Band Imaging (NBI) technology. METHODS: We enrolled, as cases, patients with clinical diagnosis of laryngopharyngeal reflux disease (LPRD), a Reflux Symptom Index (RSI) ≥ 13, and a Reflux Finding Score (RFS) ≥ 7. Controls were enrolled among patients who underwent the same transnasal endoscopy, equipped with NBI, with a RSI < 13 and a RFS < 7. Nasopharynx, Lingual Tonsils (LT), Hypopharynx and Larynx were evaluated by two experienced otolaryngologists, who calculated the Reflux Finding Scale (RFS) score and focused their attention on the base of the tongue, observing its surface with NBI technology. RESULTS: 82 patients with diagnosis of laryngopharyngeal reflux were enrolled as cases. Mean RFS was 11.7 (SD = 2.9). As controls, we enrolled 80 patients. Mean RFS was 2.7 (SD = 1.63). We found that RFS positivity was associated with a significant increase in LT dimension (2.5 vs 1.1, p < 0.001), with a higher LT crypt inflammation grading (1.8 vs 0.09, p < 0.001) and with a higher Roman Cobblestone pattern grading (1.48 vs 0.11, p < 0.001). A significant correlation between the crypt inflammation and the hyperemia subscore of RFS was present (r = 0.696, p < 0.0001), while it was not possible to find a correlation between crypt inflammation and either diffuse laryngeal edema (r = 0.166, p = 0.135) and posterior commissure hypertrophy (r = 0.089, p = 0.427). CONCLUSIONS: NBI allowed us to identify endoscopically the presence of enlarged lingual tonsil, crypt inflammation and superficial mucosal changes, in patients affected by LPRD.

OBJECTIVES: Laryngopharyngeal reflux (LPR) is a complex problem in pediatric population: diagnosis and clinical presentation are still controversial. Classic white light endoscopy shows some pathognomonic signs of LPR in children, such as thickening of pharyngo-laryngeal mucus, the cobblestoning aspect of pharyngeal mucosa, arytenoid edema/hyperemia, nodular thickening/true vocal cord edema, hypertrophy of the posterior commissure, subglottic edema. The NBI (Narrow Band Imaging) technology, generally used in oncology, allows to study neoangiogenesis and hypervascularization of the mucosa, common aspects in both chronic inflammation and neoplastic transformation. The aim of our study was to evaluate the added value of this technology in identifying the main laryngopharyngeal reflux sign in a pediatric population. METHODS: We evaluated at the Otolaryngology Unit of the "Fondazione Policlinico A. Gemelli" hospital and the Airway Surgery Unit of the "Bambino Gesù" Children's Hospital 35 patients aged from 2 months to 16 years divided into two groups in the period between November 2017 and May 2018. Group A included patients with clinical suspicion of LPR after gastroenterologist evaluation and Group B included patients who underwent an endoscopic evaluation for the assessment of recurrent respiratory symptoms such as stridor, recurrent croup, wheezing and persistent cough. We performed an endoscopic evaluation by white light and NBI for each patient, comparing the results of both methods to evaluate signs of pharyngo-laryngeal reflux and to calculate the value of reflux finding score (RFS). RESULTS: The analysis of the data showed: for Group A an average value of RFS with white light of 11,84 (range 8-17, standard deviation 2,52 ± 0,57) and with NBI of 13,63 (range 10-17, standard deviation 2,13 ± 0,49); for Group B the analysis of the data showed an average value of RFS with white light of 10,06 (range 8-14, standard deviation 2,32 ± 0,58) and with NBI of 12,50 (range

In the original version of this Article, the author Anna Rita Fetoni was incorrectly indexed. This error has now been corrected.

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Connexin hemichannels, which are plasma membrane hexameric channels (connexons) composed of connexin protein protomers, have been implicated in a host of physiological processes and pathological conditions. A number of single point pathological mutations impart a "leaky" character to the affected hemichannels, i.e., make them more active or hyperactive, suggesting that normal physiological condition could be recovered using selective hemichannel inhibitors. Recently, a human-derived monoclonal antibody named abEC1.1 has been shown to inhibit both wild type and hyperactive hemichannels composed of human (h) connexin 26 (hCx26) subunits. The aims of this work were (1) to characterize further the ability of abEC1.1 to selectively modulate connexin hemichannel function and (2) to assess its in vitro stability in view of future translational applications. In silico analysis of abEC1.1 interaction with the hCx26 hemichannel identified critically important extracellular domain amino acids that are conserved in connexin 30 (hCx30) and connexin 32 (hCx32). Patch clamp experiments performed in HeLa DH cells confirmed the inhibition efficiency of abEC1.1 was comparable for hCx26, hCx30 and hCx32 hemichannels. Of note, even a single amino acid difference in the putative binding region reduced drastically the inhibitory effects of the antibody on all the other tested hemichannels, namely hCx30.2/31.3, hCx30.3, hCx31, hCx31.1, hCx37, hCx43 and hCx45. Plasma membrane channels composed of pannexin 1 were not affected by abEC1.1. Finally, size exclusion chromatography assays showed the antibody does not aggregate appreciably in vitro. Altogether, these results indicate abEC1.1 is a promising tool for further translational studies.

Social functioning and personal satisfaction about quality of life are issues in the spotlight in most fields of otolaryngology. However, in ear surgery, few studies performed standardised measurements through interviews and validated questionnaires. We enrolled 81 patients undergoing tympanomastoidectomy from January 2011 to December 2014, at the “A. Gemelli” Hospital of the Catholic University, Rome. 50 patients (61.7%) underwent non-obliterative Canal Wall Down (CWD) mastoidectomy, whereas 31 patients (38.3%) underwent Canal Wall Up (CWU) mastoidectomy. We administered the Chronic Ear Survey (CES) 3 and 12-months post-operatively and the Chronic Otitis Media Outcome Test-15 (COMOT-15) 12 months post-operatively. Results were compared to hearing threshold, sex and age. In the CWD Group, significant improvements were observed in all CES subscale scores and total scores over time (p < 0.001) whereas in the CWU Group we found a partial improvement. Inter-group comparison showed no significant differences in administration of CES in CWD vs CWU (p > 0.05 for all subsections and overall scores). A significant difference was found only in the COMOT-15 “Hearing Function” subsection, in favour of CWU over CWD (61 vs 39 respectively; p < 0.05). A significant association was found between PTA and COMOT-15 “Hearing Function” subsection scores. According to our results, a significant difference in the post-operative QoL between CWD and CWU should not be taken for granted.

Background: Salvage total laryngectomy (TL) and laryngopharyngectomy (LP) after chemoradiotherapy may produce disfiguring defects with severe complications that require complex reconstructions. Methods: Between January 2012 and December 2018, we enrolled 25 patients who underwent internal mammary artery perforator (IMAP) flap reconstruction after salvage TL or LP. We performed retrospective review of clinical charts to collect information such as history, timing of reconstruction, type of defect, follow-up, donor and recipient site complications, and overall flap survival (OFS) rate. Three years overall survival (OS), relapse-free survival (RFS), and disease-specific survival (DSS) were calculated. Results: The OFS rate was 95%. One partial flap necrosis was recorded. No donor-site complications were found. The mean follow-up was 18 months. Three years OS was 44%, RFS was 47%, and DSS was 54%. Conclusions: IMAP flap appears to be safe, versatile, and easy to harvest, with minimal donor site morbidity. It is a reliable option in Head&Neck reconstruction, in salvage surgery as well.