Comparative real-world outcomes of dupilumab versus endoscopic sinus surgery in the treatment of severe CRSwNP patients.

INTRODUCTION: Management of severe chronic rhinosinusitis with nasal polyps (CRSwNP) has changed significantly in recent years, with different treatments now available including biologics and endoscopic sinus surgery (ESS), although there are still few comparative studies. We aimed to compare 1-year outcomes of patients with severe CRSwNP treated with dupilumab or ESS plus intranasal corticosteroids (INCS). METHODS: In this retrospective, real-life, observational, cohort study, we enrolled 101 patients with severe CRSwNP who were treated with INCS and either ESS (n = 49) or dupilumab (n = 52). The following outcomes were considered: nasal polyp score (NPS), Sino Nasal Outcome Test-22 (SNOT-22), visual analogue scale (VAS) for specific symptoms, Sniffin' Sticks identification test (SSIT), need for oral corticosteroids (OCS) and local eosinophilia detected by nasal cytology. RESULTS: ΔNPS was significantly higher in the surgery group up to 12 months when the difference with dupilumab group was no longer significant (ΔNPS: 4 vs. 4.1). ΔVAS rhinorrhoea, ΔVAS smell and ΔSNOT-22 were significantly higher in the dupilumab group at 12 months (p < .05). SSIT scores were significantly better in the dupilumab group starting from the first month of follow-up (p < .05). In the dupilumab group, only 6.1% of patients had detectable local eosinophilia compared to 57% in the surgery group alongside with a lower need for OCS (16.3% vs. 61%). CONCLUSIONS: Both dupilumab and ESS were effective in improving outcomes in patients with severe CRSwNP over 12 months. Nevertheless, patients treated with dupilumab had greater improvement in terms of SNOT-22, VAS rhinorrhoea, VAS smell and SSIT scores, with better control of local inflammation and less need for OCS.

Smell impairment in patients with chronic rhinosinusitis: a real-life study.

OBJECTIVE: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a frequently occurring condition involving type 2 inflammation. It has a global prevalence of approximately 4% and has a major effect on the quality of life of those affected by it. CRSwNP is a complex condition for otorhinolaryngologists to manage, since its precise pathogenic basis has not been established, treatment is challenging and the condition often recurs. It is common to find abnormalities in smelling in those with CRSwNP. MATERIALS AND METHODS: This cross-sectional study enrolled patients suffering from CRS. Three groups were compared: 1812 patients with CRS, 571 with CRSwNP, and 120 with CRSwNP treated by FESS. The Sniffin' Sticks® olfactory test was used to measure olfactory function in all patients. RESULTS: Olfactory dysfunction was a common symptom in patients with CRS, ranging in frequency from 56 to 74%. In patients with CRSwNP, impairment of sense of smell affected 64% of subjects (42% with anosmia, 10% with hyposmia, and 12% with cacosmia). After surgery, there was a significant improvement in the ability to smell normally. CONCLUSION: The present study confirms that impairment of smell is a common symptom in patients with chronic rhinosinusitis, mainly in subjects with nasal polyps. FESS reduces the prevalence of olfactory dysfunction.

Long-term voice outcomes and quality of life after open partial horizontal laryngectomy type II vs. total laryngectomy: A cross-sectional study.

OBJECTIVES: We aim to analyse long-term voice outcomes and quality of life (QoL) in patients undergoing open partial horizontal laryngectomy type II (OPHL type II) and to compare them to those obtained by patients undergoing total laryngectomy (TL) with voice prosthesis (VP). DESIGN: Cross-sectional cohort study. SETTING: Patients undergoing surgery for advanced laryngeal cancer, assessed during the usual follow-up consultations at the Phoniatric Unit (February 2020-December 2020). PARTICIPANTS: Forty-five patients were enrolled and divided into two groups: OPHL group and TL group. MAIN OUTCOMES MEASURES: Acoustic analysis, maximum phonation time, INFV0  scale, I-SECEL, UW-QoL-V4 and MDADI questionnaires were used to assess the long-term outcomes. RESULTS: Voices of patients undergoing OPHL Type II were worse than those of laryngectomised patients with VP. Nevertheless, scores in voice and dysphagia-related QoL were comparable and scores in the social domain of QoL were higher in OPHL group. CONCLUSIONS: Open partial horizontal laryngectomy Type II allows an acceptable voice recovery and a satisfactory QoL.

Traumatic benign paroxysmal positional vertigo: personal experience and comparison with idiopathic BPPV.

OBJECTIVE: Benign paroxysmal positional vertigo (BPPV) is the most common cause of vestibular vertigo, with post-traumatic origin in about 15% of cases. Management and prognosis of traumatic BPPV (T-BPPV) are still debated, especially about recurrence. The aim was to compare T-BPPV to idiopathic (I-BPPV). DESIGN AND STUDY SAMPLE: We analysed data about 795 BPPV patients: 716 idiopathic (90%) and 79 post-traumatic (10%), evaluating clinical history and bedside-examination, treating all patients with repositioning manoeuvres and reassessing them until the resolution of symptoms and nystagmus. RESULTS: Persistence rate in T-BPPV and I-BPPV patients was significantly different (p = 0.0074, OR = 2.31), respectively 12.6% and 5%. Also the rate of bilateral disease (p = 0.0063, OR = 4.72) and multicanalar involvement (p = 0.0183; OR = 4.67) were significantly higher in T-BPPV patients . There were no significant differences in age and sex distribution, side and canal interested. In T-BPPV group, the resolution rate with one manoeuvre was lower than I-BPPV (p = 0.0132: OR: 0,56). Recurrence rate was 38% in the T-BPPV group and 30.6% in the I-BPPV group, without significant difference. CONCLUSIONS: T-BPPV resulted different from I-BPPV in the resolution rate, bilateral or multiple canal involvement and persistence rate. T-BPPV and I-BPPV does not differ for recurrence rate, suggesting that, after resolution, the natural course of post-traumatic and idiopathic BPPV is similar.

Olfactory perception rehabilitation after total laryngectomy (OPRAT): proposal of a new protocol based on training of sensory perception skills.

PURPOSE: We aim to propose a new protocol for olfaction rehabilitation after total laryngectomy based on training of sensory perception levels using the Nasal Airflow-Inducing Maneuver. METHODS: This is a randomized clinical trial including patients undergoing total laryngectomy between March 2010 and March 2019. Patients with nasal or oral abnormalities, prior olfaction impairment, a muco-ciliary transport time higher than 30 min, positive history for feeding, and neurological disorders were excluded. Thirty-three patients were enrolled and were randomized into two groups: an Experimental group, submitted to the new protocol (olfactory perception rehabilitation after total laryngectomy-OPRAT) and a Control group that did not receive any treatment. Subjective Olfactometry, Chemosensory Complaints Score, and University of Washington Quality of Life version 4 questionnaires were used to assess the outcomes before and after treatment, and at 3-month, 6-month, and 10-month follow-up. RESULTS: Among the 33 patients included (32 men and 1 woman; mean age, 67.94 ± 5.64 years), 17 were subjected to olfaction rehabilitation and 16 did not receive any treatment. At baseline evaluation, there were not significant differences between the two groups. At the end of treatment, the rehabilitated group improved their olfaction capability significantly. Such improvement remained stable over time, and after 10 months, only the Experimental group had significant improvements in all outcome measures. CONCLUSIONS: The OPRAT may guarantee excellent results in the short- and long-term time with positive effects on the Quality of Life.

Chrono-proteomics of human saliva: variations of the salivary proteome during human development.

An important contribution to the variability of any proteome is given by the time dimension that should be carefully considered to define physiological modifications. To this purpose, whole saliva proteome was investigated in a wide age range. Whole saliva was collected from 17 preterm newborns with a postconceptional age at birth of 178-217 days. In these subjects sample collection was performed serially starting immediately after birth and within about 1 year follow-up, gathering a total of 111 specimens. Furthermore, whole saliva was collected from 182 subjects aged between 0 and 17 years and from 23 adults aged between 27 and 57 years. The naturally occurring intact salivary proteome of the 316 samples was analyzed by low- and high-resolution HPLC-ESI-MS platforms. Proteins peculiar of the adults appeared in saliva with different time courses during human development. Acidic proline-rich proteins encoded by PRH2 locus and glycosylated basic proline-rich proteins encoded by PRB3 locus appeared following 180 days of postconceptional age, followed at 7 months (±2 weeks) by histatin 1, statherin, and P-B peptide. The other histatins and acidic proline-rich proteins encoded by PRH1 locus appeared in whole saliva of babies from 1 to 3 weeks after the normal term of delivery, S-type cystatins appeared at 1 year (±3 months), and basic proline-rich proteins appeared at 4 years (±1 year) of age. All of the proteinases involved in the maturation of salivary proteins were more active in preterm than in at-term newborns, on the basis of the truncated forms detected. The activity of the Fam20C kinase, involved in the phosphorylation of various proteins, started around 180 days of postconceptional age, slowly increased reaching values comparable to adults at about 2 years (±6 months) of age. Instead, MAPK14 involved in the phosphorylation of S100A9 was fully active since birth also in preterm newborns.

A prospective open-label study to assess the efficacy and safety of a herbal medicinal product (Sinupret) in patients with acute rhinosinusitis.

AIMS: We present a multicenter, prospective, open-label study to assess the efficacy and safety of a phytomedicine. The aim of the research was to evaluate the efficacy and safety of 14 days of treatment with Sinupret for acute rhinosinusitis. Sinupret is a herbal preparation used to restore and maintain the physiological function of the membranes in the sinus cavity. METHODS: Sixty patients with acute rhinosinusitis based on the EPOS guidelines were enrolled in the study. Thirty patients were treated with Sinupret Forte, while 30 patients were treated with intranasal fluticasone furoate. The criteria for the evaluation of efficacy were the major symptom scores according to the investigator and the Health-Related Quality of Life score. The criteria used to evaluate safety were the number of patients with adverse events, the patients' vital signs, and laboratory safety. RESULTS: All patients considered showed significant improvements in symptoms. Among the patients treated with Sinupret, none had an adverse event, while 3 patients treated with fluticasone furoate had minor adverse events. The patients' vital signs and laboratory values were normal. CONCLUSIONS: The results of this study suggest that this phytomedicinal preparation has a significant level of efficacy in acute rhinosinusitis and that treatment is safe.

Surgery or No Surgery? Exploring the Dilemma of Epistaxis Management in Patients with HHT.

Background: Epistaxis, particularly in Hereditary Hemorrhagic Telangiectasia (HHT) patients, is a common otolaryngological emergency, often requiring complex management. A hierarchy of increasingly invasive interventions, from external compression of the nasal pyramid to nostril closure, is typically proposed and applied. Methods: We conducted a retrospective study on HHT patients to assess the effectiveness and longevity of invasive procedures postoperatively. Data were collected using the Epistaxis Severity Score (ESS) questionnaire. The primary focus was on changes in the frequency and intensity of epistaxis, while the secondary focus was on the overall quality of life. Results: This study found that invasive procedures initially improved the frequency and intensity of epistaxis in HHT patients. However, within 1 to 9 months postoperatively, these benefits often diminished, with hemorrhagic symptoms recurring at similar or worsened levels. Conclusions: The findings suggest a need for a cautious and restrained approach to using invasive treatments in managing epistaxis in HHT patients. Highly invasive procedures should be reserved for cases where less invasive methods fail, due to their temporary effectiveness and the risk of causing anatomical-functional changes in the rhino-sinus area, complicating future management of severe epistaxis.

How to manage recurrences after surgery in CRSwNP patients in the biologic era: a narrative review.

Objective: This narrative review analyses factors affecting recurrence of Chronic rhinosinusitis with nasal polyps (CRSwNP) after surgery, such as type, extension and completeness of endoscopic sinus surgery (ESS). We also described new implications in the management of recurrences after the advent of biologics. Methods: We identified four topics: definition of disease state; factors linked to recurrence of polyps; evaluation and management of recurrence in clinical practice. Results: We analysed the differences between exacerbation and recurrence, as well as the concept of "controlled disease". We focused on potential predictors of recurrence after ESS, such as type 2 inflammation, asthma, aspirin-exacerbated respiratory disease, incomplete initial surgery and lack of adherence to long-term post-operative local corticosteroids. We discussed the new aspects of diagnosis and treatment of recurrences after surgery, summarising our suggestions in a detailed algorithm for practical management of patients with recurrent disease. Conclusions: The results emphasised the importance of accurate evaluation of patients with CRSwNP recurrence, focusing on the reasons of failure and risk of disease progression, in order to guide personalised interventions. It is crucial to define the concept of appropriate surgery, which affects the choice between starting a biologic or repeating surgery.

Impact of SARS-CoV-2 infection in patients with hereditary hemorrhagic telangiectasia: epidemiological and clinical data from the comprehensive Italian retrospective multicenter study.

Rare Disease patients manifested high concern regarding the possible increased risk of severe outcomes and worsening of disease-specific clinical manifestation due to the impact of COVID-19. Our aim was to assess the prevalence, outcomes, and impact of COVID-19 in patients with a rare disease such as Hereditary Hemorrhagic Telangiectasia (HHT) in Italian population. A nationwide, multicentric, cross-sectional observational study was conducted on patients with HHT from five Italian HHT centers by online survey. The association between COVID-19-related signs and symptoms and nosebleeds worsening, the impact of personal protective equipment on nosebleeds pattern, and the relationship between the presence of visceral AVMs and severe outcomes were analyzed. Out of 605 total survey responses and eligible for analysis, 107 cases of COVID-19 were reported. A mild-course COVID-19 disease, not requiring hospitalization, was observed in 90.7% of patients, while the remaining eight cases needed hospitalization, two of them requiring intensive-care access. No fatal outcome was recorded and 79.3% of patients reported a complete recovery. No difference in infection risk and outcome between HHT patients and general population was evidenced. No significative interference of COVID-19 on HHT-related bleeding was found. The majority of patients received COVID-19 vaccination, with relevant impact on symptoms and need for hospitalization in case of infection. COVID-19 in HHT patients had an infection profile similar to the general population. COVID-19 course and outcome were independent from any specific HHT-related clinical features. Moreover, COVID-19 and anti-SARS-CoV-2 measures did not seem to affect significantly HHT-related bleeding profile.

Postinfectious Olfactory Complaints: A Follow-up Study.

Introduction Acute upper respiratory infection (AURI) is the most common cause of postinfectious olfactory dysfunction (PIOD). Objective We investigated the prevalence of PIOD in a large group of patients reporting persistent smell impairment perception after the AURI resolution. Methods Olfactometry was performed within 1 month after the common cold resolution and after 1 year in 467 (299 males, mean age 41.7 years) outpatients. The Sniffin' Sticks olfactory test (Burghart instruments, Wedel, Germany) was used. Results Anosmia was documented in 28 (6%) patients, hyposmia in 33 (7%), and cacosmia in 55 (11.7%). After 1 year, PIOD improved in 82 (79.6%) patients re-tested. Conclusion The current study demonstrated that persistent olfactory dysfunction is a relevant symptom in patients with AURI, even though many patients had normal olfactometry. Thus, smell impairment deserves careful attention and requires objective documentation.

Decision Making on Vestibular Schwannoma: Lessons from a Multidisciplinary Board.

BACKGROUND: Management of vestibular schwannoma (VS) is a complex process aimed at identifying a clinical indication for fractionated stereotactic radiotherapy (sRT) or radiosurgery, microsurgical resection, or wait and scan (WS). We describe the experience of our VS multidisciplinary team (MDT) at a tertiary university referral center created for diagnosis, treatment, and follow-up of VS patients. METHODS: We conducted a retrospective study on 132 consecutive patients referred to the MDT and managed by observation (WS), microsurgery, or fractionated sRT. The analysis included patient age, tumor size, hearing level, facial nerve function, tumor control, complications, and quality of life questionnaires. RESULTS: Among the patients, 21% were subjected to microsurgery, 10% to sRT, and 69% to WS. The median follow-up time was 30 months. Outcomes based on different management modalities are described. Statistically significant differences among groups were detected in terms of quality of life (physical domain). CONCLUSIONS: MDT may provide the best individualized therapy for VS patients compared with a single gold-standard strategy.

Effectiveness of Dupilumab in the Treatment of Patients with Severe Uncontrolled CRSwNP: A "Real-Life" Observational Study in the First Year of Treatment.

The aim of this study was to evaluate the efficacy of dupilumab in the treatment of severe uncontrolled Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), with or without asthma as add-on therapy with intra-nasal corticosteroids in a real-life setting over the first year of treatment. Our data demonstrated that subcutaneous 300 mg dupilumab administered at home via a pre-filled auto-injector every two weeks, based on indications set by the Italian Medicines Agency, was rapidly effective in reducing the size of polyps, decreasing symptoms of disease, improving quality of life, and recovering olfaction. Significant improvement was observed after only 15 days of treatment, and it progressively increased at 6 and 12 months. Dupilumab was also effective in reducing the local nasal eosinophilic infiltrate, in decreasing the need for surgery and/or oral corticosteroids, and in improving control of associated comorbidities such as chronic eosinophilic otitis media and bronchial asthma. After 12 months of treatment, 96.5% of patients had a moderate/excellent response. From our data, it was evident that there was a group of patients that showed a very early response within one month of therapy, another group with early response within six months from baseline, and a last group that improved later within 12 months. The results of this study support the use of dupilumab as an effective option in the current standard of care for patients affected by severe uncontrolled CRSwNP.

Mometasone Furoate in Non-Allergic Rhinitis: A Real-Life Italian Study.

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 µg 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.

Survey on Use of Local and Systemic Corticosteroids in the Management of Chronic Rhinosinusitis with Nasal Polyps: Identification of Unmet Clinical Needs.

Background: Local and systemic corticosteroids have long been the workhorse in management of chronic rhinosinusitis with nasal polyps (CRSwNP), although there is no universally accepted modality of prescription. We carried out a survey in Italy to capture current trends in the use of topical and systemic corticosteroids in patients with CRSwNP. Methods: A survey was set up on Survey Monkey®. Each author distributed the link to the survey in an ad hoc manner and a total of 437 participants filled out the survey. Results: Mometasone furoate (79.3%) was the most frequently prescribed, administered daily by 61.9% of participants; the remaining preferred to discontinue treatment for brief periods to reduce side effects or to modulate the therapy in mild cases. The majority believe that a short cycle of systemic steroids should be prescribed for re-exacerbation of symptoms and that the number of cycles in the previous year should be evaluated to define control of the disease even if international guidelines do not provide clear indications on this topic. A certain degree of divergence emerged from responses regarding how long and the maximal dose of systemic steroids which place patients at high risk for adverse events. Finally, systemic corticosteroids seem to offer only temporary benefit on recovery of smell without guaranteeing long-term control even if the patient is adherent to topical corticosteroids. Conclusions: Our results highlight the need for clear guidelines on oral steroids, which could help supporting the use of a precision medicine approach, including indications for new biological agents.

The Empty Nose Syndrome: a pragmatic classification in clinical practice.

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Benign Paroxysmal Positional Vertigo (BPPV) in COVID-19.

OBJECTIVE: The purpose of this article is to describe BPPV in COVID-19 patients by discussing the possible mechanisms underlying the onset of this vertigo. METHODS: We studied eight patients (4 F, 4 M, aged between 44 and 69 years) with COVID-19 infections complaining of vertigo. Patients were evaluated at the end of infection with an accurate clinical history, and the investigation of spontaneous, positional and positioning nystagmus. RESULTS: The vestibular findings showed benign paroxysmal positional vertigo (BPPV) in all the patients. Three patients had a mild phenotype of the COVID infection, whereas five subjects were hospitalized for the COVID infection and in three cases intensive care was required. Vestibular evaluation showed an involvement of posterior semicircular canals in five patients and horizontal in three. Three patients were treated with the Epley maneuver, two with Semont, one with Lempert and two with Gufoni maneuvers. CONCLUSIONS: We hypothesize that BPPV in COVID-19 infections can be relate to drugs, prolonged bed rest and to direct damage by viral infection on the peripheral vestibular system and in particular on the otolitic membrane due to the cytopathic effect of the virus and to the inflammatory response. Studies on large series of patients are needed to confirm our preliminary observation and to better evaluate the pathophysiological mechanisms underlying BPPV in these patients.