Exosomes multiplex profiling, a promising strategy for early diagnosis of laryngeal cancer.

BACKGROUND: Exosomes are nanosized vesicles released from all cells into surrounding biofluids, including cancer cells, and represent a very promising direction in terms of minimally invasive approaches to early disease detection. They carry tumor-specific biological contents such as DNA, RNA, proteins, lipids, and sugars, as well as surface molecules that are able to pinpoint the cellular source. By the above criteria, exosomes may be stratified according to the presence of tissue and disease-specific signatures and, due to their stability in such biofluids as plasma and serum, they represent an indispensable source of vital clinical insights from liquid biopsies, even at the earliest stages of cancer. Therefore, our work aimed to isolate and characterize LCa patients' derived exosomes from serum by Flow Cytometry in order to define a specific epitope signature exploitable for early diagnosis. METHODS: Circulating exosomes were collected from serum collected from 30 LCa patients and 20 healthy volunteers by the use of antibody affinity method exploiting CD63 specific surface marker. Membrane epitopes were then characterized by Flow cytometry multiplex analysis and compared between LCa Patients and Healthy donors. Clinical data were also matched to obtain statistical correlation. RESULTS: A distinct overexpression of CD1c, CD2, CD3, CD4, CD11c, CD14, CD20, CD44, CD56, CD105, CD146, and CD209 was identified in LCa patients compared to healthy controls, correlating positively with tumor presence. Conversely, CD24, CD31, and CD40, though not overexpressed in tumor samples, showed a significant correlation with nodal involvement in LCa patients (p < 0.01). CONCLUSION: This approach could allow us to set up a cost-effective and less invasive liquid biopsy protocol from a simple blood collection in order to early diagnose LCa and improve patients' outcomes and quality of life.

Identification and bioinformatic characterization of a serum miRNA signature for early detection of laryngeal squamous cell carcinoma.

BACKGROUND: The growing understanding of cancer biology and the establishment of new treatment modalities has not yielded the expected results in terms of survival for Laryngeal Squamous Cell Cancer (LSCC). Early diagnosis, as well as prompt identification of patients with high risk of relapse would ensure greater chance of therapeutic success. However, this goal remains a challenge due to the absence of specific biomarkers for this neoplasm. METHODS: Serum samples from 45 LSCC patients and 23 healthy donors were collected for miRNA expression profiling by TaqMan Array analysis. Additional 20 patients and 42 healthy volunteers were included for the validation set, reaching an equal number of clinical samples for each group. The potential diagnostic ability of the such identified three-miRNA signature was confirmed by ROC analysis. Moreover, each miRNA was analyzed for the possible correlation with HNSCC patients' survival and TNM status by online databases Kaplan-Meier (KM) plotter and OncomiR. In silico analysis of common candidate targets and their network relevance to predict shared biological functions was finally performed by PANTHER and GeneMANIA software. RESULTS: We characterized serum miRNA profile of LSCC patients identifying a novel molecular signature, including miR-223, miR-93 and miR-532, as circulating marker endowed with high selectivity and specificity. The oncogenic effect and the prognostic significance of each miRNA was investigated by bioinformatic analysis, denoting significant correlation with OS. To analyse the molecular basis underlying the pro-tumorigenic role of the signature, we focused on the simultaneously regulated gene targets-IL6ST, GTDC1, MAP1B, CPEB3, PRKACB, NFIB, PURB, ATP2B1, ZNF148, PSD3, TBC1D15, PURA, KLF12-found by prediction tools and deepened for their functional role by pathway enrichment analysis. The results showed the involvement of 7 different biological processes, among which inflammation, proliferation, migration, apoptosis and angiogenesis. CONCLUSIONS: In conclusion, we have identified a possible miRNA signature for early LSCC diagnosis and we assumed that miR-93, miR-223 and miR-532 could orchestrate the regulation of multiple cancer-related processes. These findings encourage the possibility to deepen the molecular mechanisms underlying their oncogenic role, for the desirable development of novel therapeutic opportunities based on the use of short single-stranded oligonucleotides acting as non-coding RNA antagonists in cancer.

Tissue expression of miR-449a as risk factor for occult neck metastasis in patients with cT3-T4 N0 laryngeal cancer. A pilot study.

OBJECTIVE: To explore the potential role of miR-449a as biomarker for laryngeal squamous cell carcinoma (LSCC), especially in the decision strategy of neck dissection (ND). METHODS: Each patient underwent total laryngectomy and bilateral ND (levels II-IV); during surgery, tissue samples of around 1 × 0.5 cm were extracted from both healthy tissue adjacent to the tumor and the visibly affected tumor tissue. The extraction of total RNA, encompassing miRNA, was performed using a mirVana PARIS kit. To detect miR449a, cDNA was synthesized from 200 ng of RNA using a TaqMan miRNA reverse transcription kit. RESULTS: The study group was formed of 66 patients (62 males, and 4 females) with LSCC, aged between 39 and 77 years (mean 60 + 14.56 yr). MiR-449a was up-regulated in twenty-eight tumors (42%), while it was down-regulated in 38 samples (58%). In the present study, there was a statistical relevance for miR-449a tissue expression for pN staging (p = 0.017), and PNI (p = 0.005). Eight tumors (12%) cN0 became pN + showing occult cervical lymph node metastases at the final histopathological examination, and all of these patients showed miR-449a downregulation. CONCLUSION: Super-selective ND (sparing the sub evels IIb and IV) might be the approach to cT3-T4 N0 LSCCs with upregulation of miR-449a; on the other hand, to ensure and effective control of occult neck metastases it would be appropriate to reserve elective ND (including sublevels IIb and IV) for cT3-T4 N0 LSCCs with miR-449a downregulation. Although promising, due to the small size of the cohort, the results of this work can be considered preliminary and need to be confirmed by prospective and larger studies.

Predictors of inappropriate shock in Brugada syndrome patients with a subcutaneous implantable cardiac defibrillator.

BACKGROUND: Subcutaneous implantable cardioverter defibrillators (S-ICDs) avoid complications secondary to transvenous leads, but inappropriate shocks (ISs) are frequent. Furthermore, IS data from patients with Brugada syndrome (BrS) with an S-ICD are scarce. OBJECTIVE: We aimed to establish the frequency and predictors of IS in this population. METHODS: We analyzed the clinical and electrocardiographic characteristics, automated screening test data, device programming, and IS occurrence in adult patients with BrS with an S-ICD. RESULTS: Thirty-nine patients were enrolled (69% male, mean age at diagnosis 46 ± 13 years, mean age at implantation 48 ± 13 years). During a mean follow-up of 26 ± 21 months, 18% patients experienced IS. Patients with IS were younger at the time of diagnosis (36 ± 8 vs. 48 ± 13 years, p = .018) and S-ICD implantation (38 ± 9 vs. 50 ± 23 years, p = .019) and presented with spontaneous type 1 Brugada electrocardiogram pattern more frequently at diagnosis or during follow-up (71% vs. 25%, p = .018). During automated screening tests, patients with IS showed lower QRS voltage in the primary vector in the supine position (0.58 ± 0.26 vs. 1.10 ± 0.35 mV, p = .011) and lower defibrillator automated screening score in the primary vector in the supine (123 ± 165 vs. 554 ± 390 mV, p = .005) and standing (162 ± 179 vs. 486 ± 388 mV, p = .038) positions. Age at diagnosis was the only independent predictor of IS (hazard ratio = 0.873, 95% confidence interval: 0.767-0.992, p = .037). CONCLUSION: IS was a frequent complication in patients with BrS with an S-ICD. Younger age was independently associated with IS. A more thorough screening process might help prevent IS in this population.

Aerodynamic findings and Voice Handicap Index in Parkinson's disease.

OBJECTIVE: To verify possible relations between vocal disability and aerodynamic measures in selected Parkinson's disease (PD) patients with low/moderate-grade dysphonia. METHODS: Fifteen idiopathic dysphonic PD male patients were examined and compared with 15 euphonic subjects. Testing included the following measures: Voice Handicap Index (VHI), maximum phonation time (MPT), mean estimated subglottal pressure (MESGP), mean sound pressure level (MSPL), mean phonatory power (MPP), mean phonatory efficiency (MPE) and mean phonatory resistance (MPR). RESULTS: Statistical analysis showed: a significant reduction in MPR and MSPL in PD subjects compared to the healthy ones; a significant positive correlation between VHI score and MSPL, MPR, MPP, MESGP and a significant negative correlation between VHI and MTP within PD subjects. Test for multiple linear regression showed a significant correlation between VHI score, MPT, MPR and MSPL. CONCLUSIONS: A relationship between VHI and aerodynamic measures was shown in the present study. Compensatory mechanisms may aggravate vocal disability in PD subjects.

Procalcitonin for Early Detection of Pharyngocutaneous Fistula after Total Laryngectomy: A Pilot Study.

OBJECTIVES: The aim of this prospective study was to investigate the role of procalcitonin as an early diagnostic marker of pharyngocutaneous fistula (PCF) in a cohort of head and neck patients treated with total laryngectomy for squamous cell carcinoma. METHODS: This prospective study was conducted on a sample of patients enrolled from January 2019 to March 2022. All patients were subjected to a "protocol" of blood chemistry investigations, scheduled as follows: complete blood count with formula, ESR dosage, CPR, and PCT. PCT was also dosed by salivary sampling and a pharyngo-cutaneous swab in patients who presented with PCF. The dosage scheme was systematically repeated: the day before the intervention (t0); the 5th day postoperative (t1); the 20th day postoperative (t2); and at time X, the day of the eventual appearance of the pharyngocutaneous fistula. RESULTS: A total of 36 patients met the inclusion criteria. The patients enrolled in the study were subsequently divided into two groups: 27 patients underwent total laryngectomy (TL) for laryngeal cancer without postoperative complications, and 9 patients were undergoing TL with postoperative PCF. Using the Cochran's Q test, statistical significance was found for PCT among T0, T1, Tx, and T2 (p-value < 0.001) between the PCF and non-PCF groups. The Z test demonstrated that there is a difference in PCT levels at T1 and T2 and that this difference is statistically significant (p < 0.001). CONCLUSIONS: PCT could be considered an early marker of complications in open laryngeal surgery. According to our results, it could be useful in the precocious detection of pharyngocutaneous fistulas and in the management of antibiotic therapy.

Aerodynamic Study of Velopharyngeal Insufficiency in 22q11.2 Deletion Syndrome.

OBJECTIVES: We aim to verify velopharyngeal sphincter function in 22q11.2 deletion syndrome patients (22q11.2DS) to establish correlations between aerodynamic and perceptual measures of nasality, and to identify aerodynamic measures differentiating typical from atypical velopharyngeal behavior. METHODS: Eleven subjects with 22q11.2DS and twenty similar-age control subjects were recruited. The aerodynamic measures were mean Sound Pressure Level, air pressure peak, pressure wave duration, airflow pattern and nasal airflow during the sequence /pi/. The nasality perceptual measures were rhinolalia, rhinophony and nasal air escape. RESULTS: Airflow patterns and perceptual measures were statistically different in the two groups. Pressure wave duration and air pressure peak were lower in study subjects than in controls. Air pressure peak and nasal airflow were negatively correlated with rhinolalia; pressure wave duration was negatively correlated with nasal air escape and rhinolalia in 22q11.2DS patients. CONCLUSIONS: This aerodynamic study identified velopharyngeal qualitative and quantitative dysfunctions, suggesting heterogeneous models of velopharyngeal function in syndromic subjects as compared to controls.

Insidious Cases of Enlarged Vestibular Aqueduct (EVA) Syndrome Resembling Otosclerosis: Clinical Features for Differential Diagnosis and the Role of High-Resolution Computed Tomography in the Pre-Operative Setting.

BACKGROUND: Enlarged vestibular aqueduct (EVA) syndrome can mimic otosclerosis in adults, presenting with an air-bone gap (ABG) and even absent stapedial reflexes. The ABG in inner-ear disorders is currently the object of several authors' studies and seems to be related to a third mobile window (TMW) phenomenon. This can lead to misdiagnosis and inappropriate treatment. Given that it would be inappropriate and harmful to perform CT scans in all patients with a clinical diagnosis of otosclerosis, this study aims to highlight some clinical features useful for the differential diagnosis between otosclerosis and these rare cases of EVA presenting with an ABG, thus enabling the identification of suspected cases to be tested with CT scans. METHODS: Between April and May 2024, a narrative review was conducted focusing on the differential diagnosis between some rare cases of EVA and otosclerosis. Clinical, audiological, and radiologic features of both conditions were investigated. RESULTS: This review demonstrates the diagnostic challenge in differentiating atypical cases of EVA from otosclerosis in a subset of patients. Clinical and audiological features are important for differential diagnosis, but may not always be sufficient. Therefore, high-resolution computed tomography (HRCT) of the temporal bone plays a pivotal role in definitive diagnosis. CONCLUSIONS: In some specific cases, pre-operative imaging assessment using HRCT emerges as an essential tool for differentiating these two conditions and avoiding unnecessary stapes surgery.

Critical Steps and Common Mistakes during Temporal Bone Dissection: A Survey among Residents and a Step-by-Step Guide Analysis.

BACKGROUND: Given that the temporal bone is one of the most complex regions of the human body, cadaveric dissection of this anatomical area represents the first necessary step for the learning and training of the young oto-surgeon in order to perform middle ear surgery, which includes the management of inflammatory pathology, hearing rehabilitation, and also cognitive decline prevention surgery. The primary objective of this study was to identify common mistakes and critical passages during the initial steps of temporal bone dissection, specifically cortical mastoidectomy and posterior tympanotomy. METHODS: A survey among 100 ENT residents was conducted, gathering insights into the most prevalent errors encountered during their training to uncover the most challenging aspects faced by novice surgeons during these procedures. RESULTS: The most common mistakes included opening the dura of the middle cranial fossa (MCF), injury of the sigmoid sinus (SS), chorda tympani (CT), and facial nerve (FN) injury while performing the posterior tympanotomy. The most important critical steps to prevent mistakes are related to the absence of wide exposure during cortical mastoidectomy and the consequent impossibility of identifying the landmarks of the facial recess before performing posterior tympanotomy. Injury of these structures was more common in younger surgeons and in the ones who performed less than five temporal bone dissection courses. CONCLUSIONS: Numerous temporal bone dissections on cadavers are mandatory for ENT residents looking forward to performing middle ear surgery.

Quality of Life and Respiratory Performance in the Laryngectomized Patient: Role of the HME Filters during Physical Activity.

Background: Permanent tracheostomy because of total laryngectomy surgery entails significant consequences for patients regarding respiratory physiopathology, such as the loss of the filtering, humidifying, and heating of air by the nose. The use of special stomal filters can provide adequate protection of the tracheal-bronchopulmonary system with a reduction in respiratory pathologies. In fact, in most cases, laryngectomy patients are first cigarette smokers who for this reason also already have respiratory diseases such as chronic obstructive pulmonary disease (COPD). Despite the availability of tracheal filters, as reported in the literature, patients often tend to limit their use due to reported breathing difficulties, especially in conditions of intense breathing. Methods: The objective of this clinical study was to evaluate the most suitable stomal filter for laryngectomy patients during physical activity. The filters studied were an INHEALTH device (Blom-Singer SpeakFree HME); two ATOS devices (Provox® Life™ Energy HME and Provox® Life™ Home HME); and an FAHL device (Laryvox HME Sport). Results: For this purpose, the performances of 31 laryngectomy patients, subjected to medium-high physical effort, were analyzed through a standardized pneumological test, the Six Minute Walking Test (6MWT), which involves a sustained walk lasting six minutes, with an evaluation of heart rate, oxygen saturation, and meters traveled every 60 s; furthermore, we examined two subjective indices, namely, the basal and final dyspnea index and the initial and final muscular fatigue index. Conclusions: The multidisciplinary approach of the laryngectomee patient must also take pulmonary rehabilitation into consideration. It is the task of the medical team and speech therapy support to help the patient in the correct choice of HME filters taking into account daily needs.

Multidisciplinary Management of Descending Necrotizing Mediastinitis: Is Thoracoscopic Treatment Feasible?

Background: Descending necrotizing mediastinitis (DNM) is a life-threatening condition, generally caused by downward dissemination of oropharyngeal infections through cervical fascial planes. Mediastinal drainage is conventionally achieved by thoracotomy, but a Video-Assisted Thoracoscopic Surgery (VATS) approach is gaining interest due to the reduced invasiveness of procedure. We aimed to evaluate the effectiveness of VATS treatment in patients with DNM. Methods: We conducted a retrospective multicenter study including patients with descending mediastinitis that underwent mediastinal drainage through VATS (VATS group) or thoracotomy (thoracotomy group), both in association with cervical drainage. Patients with mediastinitis secondary to cardiac, pulmonary, or esophageal surgery were excluded. The intergroup differences regarding surgical outcome and postoperative morbidity and mortality were compared. Results: A total of 21 patients were treated for descending mediastinitis during the study period. Cervicotomy and thoracotomy were performed in 15 patients (71%), while cervicotomy and VATS were performed in 6 patients (29%). There were no significant differences in surgical outcome, postoperative morbidity, and mortality between groups. VATS treatment was not associated with a higher complication rate. Patients in the VATS group had a shorter operative time (p = 0.016) and shorter ICU stay (p = 0.026). Conclusions: VATS treatment of DNM is safe and effective. The comparison with thoracotomy showed no significant differences in postoperative morbidity and mortality. The VATS approach is associated with a shorter operative time and ICU stay than thoracotomy.

Effects of guidelines on adeno-tonsillar surgery on the clinical behaviour of otorhinolaryngologists in Italy.

BACKGROUND: Several guidelines on adeno-tonsillar disease have been proposed in recent years and some discrepancies in relation both to clinical manifestations and indications for surgical treatment have emerged. The aim of the study was to verify what influence (adeno)-tonsillectomy guidelines have had on the clinical behaviour of ENT specialists in Italy. Our study is a retrospective and multi-centre case series with chart review. METHODS: The survey involved 14,770 children, aged between the ages of 2 and 11, who had undergone adeno-tonsillar surgery between 2002 and 2008 in fourteen Italian tertiary and secondary referral centres. Anova test was used for the statistical analysis, assuming p < 0.05 as the minimum statistical significance value. RESULTS: The frequency of adeno-tonsillar surgeries did not change significantly (p>0.05) during the study period and following the Italian policy document publication. Overall, adeno-tonsillectomy was the most frequent intervention (64.1%), followed by adenoidectomy (31.1%) and tonsillectomy (4.8%). The indications for surgery did not change significantly for each of the operations (p>0.05), with the exception of adeno-tonsillectomy in case of feverish episodes due to acute recurrent tonsillitis ≥ 5 without nasal obstruction (decreased p= 0.010) , even when the feverish episodes due to acute recurrent tonsillitis were < 5 over the last year. Nasal obstruction was associated with feverish episodes due to acute recurrent tonsillitis in 65.2% of operated cases, while otitis media had been diagnosed in 43.3% of the patients studied. CONCLUSIONS: The recommendations first developed in Italy in a 2003 policy document and then resumed in guidelines in 2008, were not implemented by ENT units involved in the survey. The study highlights the fact that the indications for adeno-tonsillar operations are based on the overall clinical presentation (comorbidity) rather than on a single symptom. Guidelines are necessary to give coherent recommendations based on both the findings obtained through randomized controlled trials and the data collected from observational studies.

Effects of Adenotonsillectomy on Vocal Function.

INTRODUCTION: Correct breathing is a fundamental condition for adequate vocal production. Respiratory dynamics are able to modify the growth of facial mass and lingual posture, i.e., of the skull, the mandibular one. For this reason, infant mouth breathing can cause hoarseness. MATERIALS AND METHODS: We evaluated the actual changes in the characteristics of the voice and articulation of language in a group of subjects affected by adenotonsillar hypertrophy (grade 3-4), with frequent episodes of pharyngo-tonsillitis who underwent adenotonsillectomy. Our study included 20 children-10 boys and 10 girls-aged 4 to 11 years who had adenotonsillar hypertrophy and pharyngotonsillitis episodes exceeding 5-6 per year in the previous 2 years. The control group (Group B) included 20 children-10 boys and 10 girls-aged 4 to 11 years (average age of 6.4 years) who had not undergone surgery and shared the same degree of adenotonsillar hypertrophy as those in Group A but who did not experience recurrent pharyngotonsillitis episodes. DISCUSSION: The hypertrophy of adenoids and tonsils significantly impacted breathing, vocal function, and speech articulation. All this is responsible for a state of tension in the neck muscles, which at the level of the vocal tract causes hoarseness. The changes objectively observed in our study in the pre- and post-operative phase demonstrate how adenotonsillar hypertrophy is responsible for an increase in resistance to the passage of air at the glottic level. CONCLUSIONS: For this reason, adenotonsillectomy has an impact on recurrent infections and can also lead to an improvement in speech, breathing, and posture.

QoL Following Dacryocystorhinostomy: Linguistic Adaptation of Italian Version of GBI.

The Glasgow Benefit Inventory (GBI) is a generic patient recorded outcome measure assessing the quality of life of patients undergoing ear nose and troth surgery. Although largely used in the clinical practice, it has never been adapted and validated in the Italian language. The aim of the study was to translate the original GBI from English to Italian and to examine its reliability for use in the Italian adult population of patients undergoing endonasal endoscopic dacryocystorhinostomy. After translation and back-translation of the original English we evaluated the reliability of GBI for use in 79 Italian adults undergoing dacryocystorhinostomies. Reliability of GBI-IT was examined by the internal consistency of the scale (using the Cronbach's alpha coefficient), and by the test-retest analysis. The GBI-IT showed adequate internal consistency (Cronbach's alpha = 0.85 for the total scale). The total GBI-IT score showed a strong correlation in retests (CCC 0.87). In conclusion, our study showed that the GBI-IT has satisfactory internal consistency and reliability and is equivalent to the original English version. In addition, it can be considered a valuable measure for both clinical and research uses.

Transoral Approach to Parapharyngeal Space Tumours: Preliminary Reports from a Single-Centre Retrospective Analysis.

PURPOSE: The aim of this study is to identify certain parapharyngeal space tumours with specific characteristics that can be treated successfully through an endoscopically assisted transoral approach (EATA). METHODS: Nine patients with PPS tumours underwent surgery through an EATA between 2003 and 2021. All patients underwent clinical examination and fibrolaryngoscopy. Preoperative CT and/or MRI was performed on all patients. RESULTS: All the patients were successfully treated through an endoscopically assisted transoral approach. Histological examination revealed five pleomorphic adenomas, two schwannomas, one ectopic thyroid gland and one lipoma. The only long-term sequelae observed was Horner syndrome in the two schwannomas arising from the carotid space. The mean hospitalisation time was 2.6 days, while the mean follow-up time was of 9.7 years. CONCLUSIONS: An endoscopically assisted transoral approach (EATA) is a valid technique for treating benign capsulated tumours of the true PPS and some benign capsulated tumours of the superomedial aspect of the carotid space.

Extracapsular Tonsillectomy versus Intracapsular Tonsillotomy in Paediatric Patients with OSAS.

OBJECTIVE: The objective of our study was to compare our experience of intracapsular tonsillotomy performed with the help of a microdebrider usually used for adenoidectomy with results obtained from extracapsular surgery through dissection and from adenoidectomy in cases of people affected with OSAS, linked to adeno-tonsil hypertrophy, observed and treated in the last 5 years. METHODS: 3127 children with adenotonsillar hyperplasia and OSAS-related clinical symptoms (aged between 3 and 12 years) underwent tonsillectomy and/or adenoidectomy. A total of 1069 patients (Group A) underwent intracapsular tonsillotomy, while 2058 patients (Group B) underwent extracapsular tonsillectomy, from January 2014 to June 2018. The parameters considered in order to evaluate the effectiveness of the two different surgery techniques taken into consideration were as follows: the presence of possible postoperative complications, represented mainly by pain and perioperative bleeding; the level of postoperative respiratory obstruction compared with the original obstruction through night pulse oximetry, performed 6 months before and after the surgery; tonsillar hypertrophy relapse in Group A and/or the presence of residues in Group B with clinical evaluation performed 1 month, 6 months, and 1 year after the surgery; and postoperative life quality, evaluated through submitting to parents the same survey proposed before the surgery 1 month, 6 months, and 1 year after the surgery. RESULTS: Regardless of the technique used (extracapsular tonsillectomy or intracapsular tonsillotomy), there was a clear improvement in both the obstructive respiratory symptomatology and quality of life in both patient groups, as highlighted by the pulse oximetry and the OSA-18 survey submitted later. CONCLUSIONS: Intracapsular tonsillotomy surgery has improved in terms of a reduction in postoperative bleeding cases and pain reduction, with an earlier return to patients' usual lifestyle. Lastly, using a microdebrider with the intracapsular technique seems to be particularly effective in removing most of the tonsillar lymphatic tissue, leaving only a thin border of pericapsular lymphoid tissue and preventing lymphoid tissue regrowth during one year of follow-up.

Parosmia COVID-19 Related Treated by a Combination of Olfactory Training and Ultramicronized PEA-LUT: A Prospective Randomized Controlled Trial.

During COVID-19 pandemic, clinicians have had to deal with an ever-increasing number of cases of olfactory disturbances after SARS-CoV-2 infections and in some people this problem persisted for long time after negativization from virus. This a prospective randomized controlled trial aims at evaluating the efficacy of ultramicronized palmitoylethanolamide (PEA) and Luteolin (LUT) (umPEA-LUT) and olfactory training (OT) compared to OT alone for the treatment of smell disorders in Italian post-COVID population. We included patients with smell loss and parosmia who were randomized and assigned to Group 1 (intervention group; daily treatment with umPEA-LUT oral supplement and OT) or Group 2 (control group; daily treatment with placebo and OT). All subjects were treated for 90 consecutive days. The Sniffin' Sticks identification test was used to assess the olfactory functions at the baseline (T0) and the end of the treatment (T1). Patients were queried regarding any perception of altered olfaction (parosmia) or aversive smell, such as cacosmia, gasoline-type smell, or otherwise at the same observational points. This study confirmed the efficacy of combination of umPEA-LUT and olfactory training as treatment of quantitative smell alteration COVID-19 related, but the efficacy of the supplement for parosmia was limited. UmpEA-LUT is useful for the treatment of brain neuro-inflammation (origin of quantity smell disorders) but has limited/no effect on peripheral damage (olfactory nerve, neuro-epithelium) that is responsible of quality disorders.

Are Excessive Daytime Sleepiness and Lower Urinary Tract Symptoms the Triggering Link for Mental Imbalance? An Exploratory Post Hoc Analysis.

BACKGROUND: Both lower urinary tract symptoms (LUTS) and excessive daytime sleepiness (EDS) could negatively impair the patients' quality of life, increasing the sensitivity to psychological distress that results in mental health disorders. The relationships of both urinary and respiratory domains with psychological distress in obstructive sleep apnea patients is still underestimated. METHODS: This study was a post hoc analysis of a web-based Italian survey, which included 1998 participants. Three hierarchical multiple linear regression analyses with psychological distress as dependent variable were performed on the study of 1988 participants enrolled in the final analysis. Cohen's f2 was used for the assessment of the effect size. RESULTS: From the hierarchical multiple linear regression analyses, it emerged that the final statistical model (including sociodemographic characteristics, comorbidities, perceived urinary function, and excessive daytime sleepiness) for all dimensions accounted for 16.7% of the variance in psychological distress, with a medium effect size (f2 = 0.15). CONCLUSIONS: People reported psychological distress was impaired by the presence of LUTS and EDS. Specifically, our study showed that higher levels of distress were scored especially in young women exhibiting urinary symptoms and with high values of daytime sleepiness.

Evolutionary factor analysis of replicated time series.

In this article, we develop a novel method that explains the dynamic structure of multi-channel electroencephalograms (EEGs) recorded from several trials in a motor-visual task experiment. Preliminary analyses of our data suggest two statistical challenges. First, the variance at each channel and cross-covariance between each pair of channels evolve over time. Moreover, the cross-covariance profiles display a common structure across all pairs, and these features consistently appear across all trials. In the light of these features, we develop a novel evolutionary factor model (EFM) for multi-channel EEG data that systematically integrates information across replicated trials and allows for smoothly time-varying factor loadings. The individual EEGs series share common features across trials, thus, suggesting the need to pool information across trials, which motivates the use of the EFM for replicated time series. We explain the common co-movements of EEG signals through the existence of a small number of common factors. These latent factors are primarily responsible for processing the visual-motor task which, through the loadings, drive the behavior of the signals observed at different channels. The estimation of the time-varying loadings is based on the spectral decomposition of the estimated time-varying covariance matrix.

Intravascular Papillary Endothelial Hyperplasia (Masson's Tumor) of the Supraclavicular Region: Management of a Rare Case.

BACKGROUND Masson's tumor, also known as IPEH (intravascular papillary endothelial hyperplasia), is a rare benign vascular process, comprising approximately 2% of vascular tumors of the skin and subcutaneous tissue. IPEH presenting as a neck mass is rare, with only 5 reports of anterior neck mass and 7 cases of lateral neck lesions, of which 1 was in an external jugular vein aneurysm. To the best of our knowledge, the localization of intravascular papillary endothelial hyperplasia in the supraclavicular region is rarely reported. CASE REPORT We describe our management of a non-traumatic and non-painful mass on the right supraclavicular region in 24-year-old woman. Ultrasound revealed a heterogeneously hypoechoic mass with intense vascularization. Magnetic resonance imaging (MRI) showed a formation with lobulated contours and closely related to muscular layers of serratus anterior muscle. The findings of ultrasound-guided biopsy (FNA) were inconclusive. Complete removal of the mass was performed. Histopathological examination showed a well-circumscribed lesion with numerous small papillary structures. The papillae had hyalinized hypocellular cores covered by flattened endothelium. Immunohistochemical analysis showed endothelial positivity for CD34 and CD31. These features are typical of IPEH. No recurrence had occurred at 12 months after surgery. CONCLUSIONS The differential diagnosis of malignant tumors like angiosarcoma is important because the prognosis significantly differs. Surgical excision is the treatment of choice. In our experience, the size of the lesion and its critical landmarks have not influenced the outcomes of the surgical procedure in terms of potential functional damages.