The Prognostic Value of Olfactory Dysfunction in Patients with COVID-19: The COVIDORA Study.

BACKGROUND: Among all studies describing COVID-19 clinical features during the first wave of the pandemic, only a few retrospective studies have assessed the correlation between olfac-tory dysfunction (OD) and the evolution of disease severity. The main aim was to assess whether OD is a predictive factor of COVID-19 severity based on the patient's medical management (outpa-tient care, standard hospital admission, and ICU admission). METHODS: A national, prospective, mul-ticenter cohort study was conducted in 20 public hospitals and a public center for COVID-19 screen-ing. During the first wave of the pandemic, from 6 April to 11 May 2020, all patients tested positive for COVID-19 confirmed by RT-PCR underwent two follow-up ENT consultations within 10 days of symptom onset. The main outcome measures were the evolution of medical management (out-patient care, standard hospital admission, and ICU admission) at diagnosis and along the clinical course of COVID-19 disease. RESULTS: Among 481 patients included, the prevalence of OD was 60.7%, and it affected mostly female patients (74.3%) under 65 years old (92.5%), with fewer comor-bidities than patients with normal olfactory function. Here, 99.3% (290/292) of patients with OD presented with non-severe COVID-19 disease. Patients reporting OD were significantly less hospi-talized than the ones managed as outpatients, in either a standard medical unit or an ICU. Conclu-sions: As regards the clinical course of COVID-19 disease, OD could predict a decreased risk of hospitalization during the first wave of the pandemic.

The Role of Ear, Nose, and Throat Specialists in the Nose-to-Brain Pathway.

This Viewpoint discusses the role of ear, nose, and throat specialists in the understanding, development, growth, and administration of direct nose-to-brain delivery route devices and therapies.

The SQ HDM SLIT-Tablet is safe and well tolerated in patients with House Dust Mite allergic rhinitis with or without asthma: A "real-life" French study.

BACKGROUND: The SQ House Dust Mite (HDM) SubLingual ImmunoTherapy (SLIT)-Tablet (Acarizax) is the only allergen immunotherapy authorized by European regulatory authorities to treat HDM-induced allergic asthma (AA) that is not well-controlled by inhaled corticosteroids and associated with mild-to-severe HDM allergic rhinitis (AR). The aim of this study was to add evidence on the safety of the SQ HDM SLIT-Tablet in patients with AR, alone or with AA, under real-life conditions. METHODS: This was a French "real-life", multicenter, non-comparative, longitudinal, prospective study. It included patients initiating the SQ HDM SLIT-Tablet for either persistent moderate-to-severe HDM AR or AA not well-controlled by inhaled corticosteroids and associated with mild-to-severe HDM AR. Adverse Events (AEs) were collected at the first intake and throughout the study. Logistic regression was used to compare safety according to asthma control before treatment initiation. RESULTS: Between May 09, 2018 and May 29, 2019, 1526 patients were enrolled at 185 sites and 1483 were included in the safety population (SAF). Of them, 33.6% had suspected clinical manifestations of AA. Asthma was uncontrolled for 18.2% of the patients, partially controlled for 27.9% and well-controlled for 53.8%. Overall, 31.9% of the SAF patients experienced at least one AE. The percentage of patients with AEs was 29.9% among patients with AR alone and 35.9% among those with AA (p = 0.0193). No significant difference was observed in the rate of AE or SAE depending on asthma control at inclusion (2.2% of SAEs reported for patients with uncontrolled asthma, 1.4% for partly controlled and 1.1% for well-controlled). CONCLUSIONS: The overall results indicate a good SQ HDM SLIT-Tablet safety profile consistent with that reported in previous studies, regardless of asthma control.

Decongestant use and the risk of myocardial infarction and stroke: a case-crossover study.

Pharmacovigilance reports of cerebral and cardiovascular events in those who use decongestants have triggered alerts related to their use. We aimed to assess the risk of stroke and myocardial infarction (MI) associated with the use of decongestants. We conducted a nested case-crossover study of patients with incident stroke and MI identified in France between 2013 and 2016 in two systematic disease registries. Decongestant use in the three weeks preceding the event was assessed using a structured telephone interview. Conditional logistic multivariable models were used to estimate the odds of incident MI and stroke, also accounting for transient risk factors and comparing week 1 (index at-risk time window, immediately preceding the event) to week 3 (reference). Time-invariant risk factors were controlled by design. In total, 1394 patients with MI and 1403 patients with stroke, mainly 70 years old or younger, were interviewed, including 3.2% who used decongestants during the three weeks prior to the event (1.0% definite exposure in the index at-risk time window, 1.1% in the referent time window; adjusted odds ratio (aOR), 0.78; 95%CI, 0.43-1.42). Secondary analysis yielded similar results for individual events (MI/stroke). We observed no increased risk of MI or stroke for patients 70 years of age and younger without previous MI or stroke who used decongestants.

Small Private Online Course in Teaching Oncology-Feedback After 1 Year: What Lessons?

In response to the complexity of medical care in oncology, 2 years ago, we designed a new teaching method (SPOC, Small Private Online Course) to improve cancer treatment and its management by emphasizing the community-hospital interface. The educational objective of this study was to evaluate after 1 year if the interest for this teaching remained constant over the long term to meet both educational and financial requirements. We designed a questionnaire including 18 questions grouped in 3 main parts describing the profile of the participants, his/her own experience, and the current utilization of the SPOC. Of 1574 participants of the 2 first sessions, 182 (11.5%) completed the questionnaire after 1 year. The majority of respondents were between the ages of 31 and 60 and belonged to a paramedical group (47.81%). After 1 year, 84.6% participants were satisfied or very satisfied with the content of the SPOC, 83.6% would recommended it, and 67% would be interested in using an updated SPOC again. Only 4.9% kept some contacts with other participants and 4.9% with teachers. 31.3% considered that the SPOC had a medium impact on their professional activity, 33.5% a lot, and 2.7% completely whereas 24.7% considered that it had little impact. The evaluation at 1 year showed that this digital learning method had a global positive impact on the professional practice of the participants. This study highlighted the empowerment of participants after this kind of teaching, but the network between participants was not enhanced.

Cost-effectiveness of trans-nasal endoscopic sphenopalatine artery ligation vs arterial embolisation for intractable epistaxis: Long-term analyses.

OBJECTIVES: Trans-nasal endoscopic sphenopalatine artery ligation (TESPAL) and endovascular arterial embolisation both provide excellent success rates for intractable epistaxis. Recent economic models suggest that TESPAL could be a cost-saving strategy. Our main aim was to perform cost-effectiveness analyses on TESPAL compared with embolisation to treat patients with epistaxis. DESIGN: We performed retrospective, monocentric, comparative analyses on patients referred to our centre and treated with embolisation or TESPAL. SETTING: This economic evaluation was carried out from a payer's perspective (ie French National Health Insurance) within a time horizon of 12 months. PARTICIPANTS: Thirty-seven TESPAL procedures and thirty-nine embolisation procedures to treat intractable epistaxis were used in the analyses. MAIN OUTCOME MEASURES: The primary outcome is presented as the cost per 1% of non-recurrence. Effectiveness was defined as avoiding recurrence of epistaxis during the 1-year follow-up. Cost estimates were performed from the payer's perspective. RESULTS: Hospitalisation costs were higher for embolisation compared with TESPAL (5972 vs 3769 euros). On average, hospitalisation costs decreased by 41% when a patient was treated by TESPAL compared with an embolisation strategy (P = 0.06). The presence of comorbidities increased hospitalisation costs by 79% (P = 0.04). TESPAL enabled 1867€ to be gained in intractable epistaxis. CONCLUSIONS: The outcomes from our decision model confirm that TESPAL is more cost-effective for patients with intractable epistaxis.

Renal cell carcinoma metastatic to the sinonasal cavity: A review and report of 8 cases.

Renal cell carcinoma (RCC) metastatic in the sinonasal cavity is rare. In many cases, it represents the initial presentation of RCC. We conducted a retrospective chart review to report the clinical presentation, imaging, and treatment of RCC metastases in the sinonasal cavity at two tertiary care referral centers. Our population was made up of 8 patients-6 men and 2 women, aged 55 to 86 years (mean: 66.9; median: 63.5)-who had been diagnosed with cancer in the sinonasal cavity. The most common complaints were epistaxis, nasal obstruction, and diplopia. Cancers were located in the ethmoid sinus (n = 3), nasal cavity (n = 2), sphenoid sinus (n = 2), and maxillary sinus (n = 1). Local treatment involved resection and adjuvant radiotherapy in 4 patients, surgery alone in 2 patients, and radiotherapy alone in the other 2. The lesion was embolized before surgery in 4 cases. We also performed a critical review of similar published cases. Our literature review covered 53 cases of RCC metastatic to the sinonasal cavity, including ours. Metastases were the first presentation of RCC in 24 of these cases (45.3%); in our series, the metastases led to the diagnosis of the primary RCC in 3 cases (37.5%). In the 53 reported cases, metastatic resection was performed on 35 patients (66.0%). Survival data were available for 22 of these operated patients, and 17 of them achieved a complete local response. Adjunctive radiotherapy was not associated with a better local response. Overall survival was significantly better in patients who had an isolated metastasis rather than multiple metastases (p = 0.013). There was no difference in overall survival between patients whose metastasis represented the initial presentation of RCC and those whose metastasis did not (p = 0.95). We recommend that sinonasal metastasis be suspected in the event of unilateral nasal bleeding or nasal obstruction in patients diagnosed with RCC. Embolization may prevent abundant bleeding during removal. Surgery may improve the quality of life of these patients while decreasing nasal obstruction and bleeding.

The Impact of a Small Private Online Course as a New Approach to Teaching Oncology: Development and Evaluation.

BACKGROUND: Oncology involves complex care and multidisciplinary management of patients; however, misinformation and ineffective communication remain problematic. OBJECTIVE: The educational objective of our study was to develop a new teaching method to improve cancer treatment and management by emphasizing the link between hospitals (inpatients) and their surrounding communities (outpatients). METHODS: A team of 22 professionals from public and private institutions developed a small private online course (SPOC). Each offering of the course lasted 6 weeks and covered 6 topics: individual health care plans, cancer surgery, ionizing radiation, cancer medicines, clinical research, and oncological supportive care. For participants in the course, we targeted people working in the cancer field. The SPOC used an active teaching method with collaborative and multidisciplinary learning. A final examination was offered in each session. We evaluated participants' satisfaction rate through a questionnaire and the success of the SPOC by participants' completion, success, and commitment rates. RESULTS: Of the total participants (N=1574), 446 completed the evaluation form. Most participants were aged 31 to 45 years. Participants included 56 nurses, 131 pharmacists, 80 from the medical field (including 26 physicians), 53 from patients' associations, 28 health teachers, and 13 students (medical and paramedical). Among the participants, 24.7% (90/446) had an independent medical practice, 38.5% (140/446) worked in a public institution, and 36.8% (134/446) worked in a private institution. After completing the SPOC sessions, 85.9% (384/446) thought they had learned new information, 90.8% (405/446) felt their expectations were met, and 90.4% (403/446) considered that the information had a positive impact on their professional practice. The completion rate was 35.51% (559/1574), the success rate was 71.47% (1025/1574), and the commitment rate was 64.67% (1018/1574). Concerning the cost effectiveness of SPOC compared with a traditional classroom of 25 students, online education became more effective when there were more than 950 participants. CONCLUSIONS: SPOCs improved the management of oncology patients. This new digital learning technique is an attractive concept to integrate into teaching practice. It offered optimal propagation of information and met the students' expectations.

Multicenter assessment of exclusive endoscopic endonasal approach for the treatment of 53 olfactory neuroblastomas.

BACKGROUND: Given the particularities of olfactory neuroblastoma (ONB) and the lack of studies on the subject, a multicenter collaborative study was conducted to assess treatment strategy. METHODS: Fifty-three patients with ONB were included from the French Rare Head and Neck Cancer Expert Network (REFCOR) database: 16T1, 8T2, 19T3, and 10T4. All cases were treated endoscopically with skull base removal and repair in 26 cases (49%) and without external craniotomy. RESULTS: The overall survival (OS) and disease-free survival (DFS) rates at 5 years were 87% and 71%, respectively, with mean follow-up of 45.4 ± 26.5 months. The complication rate was 18.8% with 4 cases of meningitis. Pathological analysis showed positive margins in 26.8%, notably on the dura-mater and periorbita, without impairment of OS or DFS. Forty-eight patients received adjuvant radiotherapy on T ± N. Ten patients had a recurrence (18.9%). Six patients died of their disease. Prophylactic neck irradiation seemed to reduce the recurrence rate. CONCLUSION: Exclusively endoscopic treatment proved efficient and reliable in a large controlled series.

Adipose stromal cells improve healing of vocal fold scar: Morphological and functional evidences.

OBJECTIVES/HYPOTHESIS: Adipose derived stromal cells (ASCs) are abundant and easy to prepare. Such cells may be useful for treating severe vocal disturbance caused by acute vocal fold scars. STUDY DESIGN: Prospective animal experiments with controls. METHODS: Twenty New-Zealand white rabbits were used in the present study. We evaluated vocal fold healing, with or without injection of autologous ASCs, after acute scarring. A defined lesion was created and the ASCs were immediately injected. Vocal fold regeneration was evaluated histomorphometrically and via viscoelastic analysis using an electrodynamic shaker. RESULTS: Six weeks after ASC injection, vocal folds exhibited significantly less inflammation than control folds (P < 0.005). In addition, hypertrophy of the lamina propria and fibrosis were significantly reduced upon ASC injection (P < 0.02). The decrease in viscoelastic parameters was less important in the ASC injected group compared to the noninjected group (P = 0.08). CONCLUSION: Injection of autologous ASCs improved vocal fold healing in our preclinical model. Further studies are needed, but this method may be useful in humans. LEVEL OF EVIDENCE: NA. Laryngoscope, 126:E278-E285, 2016.

Arterial embolization with Onyx of head and neck paragangliomas.

OBJECT: To report the morbidity and long term results in the treatment of paragangliomas by transarterial embolization with ethylene vinyl alcohol (Onyx), either as preoperative or palliative treatment. METHODS: Between September 2005 and 2012, 18 jugulotympanic, 7 vagal, and 4 carotid body paragangliomas (CBPs) underwent Onyx embolization, accordingly to our head and neck multidisciplinary team's decision. CBPs were embolized preoperatively. Jugulotympanic and vagal paragangliomas underwent surgery when feasible, otherwise palliative embolization was carried out alone, or in combination with radiotherapy or tympanic surgery in the case of skull base or tympanic extension. Treatment results, and clinical and MRI follow-up data were recorded. RESULTS: In all cases, devascularization of at least 60% of the initial tumor blush was obtained; 6 patients underwent two embolizations. Post-embolization, 8 patients presented with cranial nerve palsy, with partial or complete regression at follow-up (mean 31 months, range 3-86 months), except for 2 vagal and 1 hypoglossal palsy. 10 patients were embolized preoperatively; 70% were cured after surgery and 30% showed residual tumor. 19 patients received palliative embolization, of whom 5 underwent radiotherapy and 3 received tympanic surgery post-embolization. Long term follow-up of palliative embolization resulted in tumor volume stability (75%) or extension in intracranial or tympanic compartments. Onyx embolization of CBPs resulted in more difficult surgical dissection in 2 of 4 cases. CONCLUSIONS: Onyx embolization is a valuable alternative to surgery in the treatment of jugulotympanic and vagal paragangliomas; tympanic surgery or radiosurgery of the skull base should be considered in selected cases. Preoperative Onyx embolization of CBPs is not recommended.

Is neuroendocrine differentiation useful to discriminate primary sinonasal intestinal-type adenocarcinomas from metastatic colorectal adenocarcinomas?

Primary sinonasal intestinal-type adenocarcinomas (ITAC) are defined on the basis of their morphological similarities to colorectal adenocarcinomas (CRA). Thus, differential diagnosis with sinonasal metastasis of CRA could be a real challenge. Neuroendocrine differentiation has been variably described in several types of adenocarcinomas and notably in ITACs and CRAs. In a series of 25 ITACs and 25 lymph node metastasis of CRAs (nmCRA), we analysed neuroendocrine differentiation by immunohistochemistry with anti-chromogranin A and synaptophysin antibodies. Neuroendocrine differentiation (chromogranin A and/or synaptophysin positivity) was significantly different (p=0.0002) in ITACs (72%) and in nmCRAs (20%). In conclusion, presence of neuroendocrine cells seems more in favour of a sinonasal intestinal-type adenocarcinoma, than metastatic CRA. This immunohistochemical study could be useful in difficult cases and should be an interesting complement in a clinical discussion.

Our experience with respiratory epithelial adenomatoid hamartomas of the olfactory cleft.

Respiratory epithelial adenomatoid hamartoma (REAH) is a relatively recent diagnosis that is gaining more interest in sinus surgery. REAH of the olfactory cleft was often misdiagnosed, and interpreted as nasal polyposis (NP). We present a retrospective case series of 27 patients who were diagnosed and treated for REAH of the olfactory cleft, in the past 7 years, in our department. The aim of this study is to present the diagnostic modalities and the results and follow-up after surgery. The male to female ratio was 2.9:1, with a mean age of 56 years. Almost half of these patients were operated at least once before on their sinuses. The most common presenting symptoms of isolated REAH are olfactory disorders. All cases were treated surgically with endoscopic sinus surgery, without recurrences in the follow-up period. Knowledge and identification of REAH of the olfactory cleft are fundamental. Knowledge, identification, and adequate treatment of these lesions are fundamental, as they limit the number of recurrences.

A comparative immunohistochemistry study of diagnostic tools in salivary gland tumors: usefulness of mammaglobin, gross cystic disease fluid protein 15, and p63 cytoplasmic staining for the diagnosis of mammary analog secretory carcinoma?

BACKGROUND: Mammary analog secretory carcinoma (MASC) of the salivary gland has been recently described according to morphological, immunohistochemical, and molecular (ETV6-NTRK3 translocation) similarities with the mammary secretory carcinoma. The most important differential diagnostic considerations of MASC are low-grade adenocarcinoma not otherwise specified (NOS), cystadenocarcinoma, and acinic cell carcinoma (AciCC). These tumors may share an overlapping morphology with MASC, and additional immunohistochemical studies are required to reinforce the diagnosis. Mammaglobin, GCDFP-15, and p63 staining have been reported in MASC. Our study was designed to check the specificity of these antibodies in MASC compared to other frequent tumors of salivary glands. METHODS: A series of 62 salivary gland tumors [10 MASCs, 5 adenocarcinomas NOS and 2 cystadenocarcinomas with MASC features and without ETV6 rearrangement, one low-grade cribriform cystadenocarcinoma (LGCCC), 9 AciCCs, 10 MECs, 10 adenoid cystic carcinomas (AdeCCs), 5 polymorphous low-grade adenocarcinomas (PLGAs), and 10 pleomorphic adenomas (PAs)] was analyzed by immunohistochemistry with mammaglobin, GCDFP-15, and p63 antibodies. RESULTS: Positivity for mammaglobin was observed in all MASCs, cystadenocarcinomas, LGCCC, and PLGAs, in some adenocarcinomas NOS, PAs, and MECs, rarely in AciCCs and never in AdeCCs. Positivity for GCDFP-15 was observed in most of the tumor types except in AdeCCs. Interestingly, cytoplasmic positivity for p63 was observed in most of MASCs and PLGAs while rarely in adenocarcinomas NOS and PAs, and never in the other tumor types. CONCLUSION: Our study revealed the usefulness of mammaglobin and p63 cytoplasmic staining to define which tumors are worth to be screened for ETV6 rearrangement.

Long-term oncological outcome after endoscopic surgery for olfactory esthesioneuroblastoma.

CONCLUSIONS: Endoscopic techniques seem to be safe approaches for the treatment of esthesioneuroblastomas (ENBs). However, they are intended for selected patients and require extensive experience in base of the skull surgery. OBJECTIVES: ENB is a rare tumor of the nasal cavity. The craniofacial approaches remain the gold standard of treatment in multiple centers. Endoscopic endonasal approaches were progressively developed. The main objective of this work was to study the overall survival and recurrence-free period for patients with ENB who underwent endoscopic resection. METHODS: We performed a retrospective study from 1996 to 2014, reviewing the patients treated by endonasal endoscopic surgery for ENB. RESULTS: Eight patients benefited from endoscopic surgical resection. According to the Kadish classification, one patient was stage A, three patients were stage B, and four patients were stage C. According to the Dulguerov classification, one patient was stage T1, five patients were stage T2, and two were stage T4. Reconstruction of the base of the skull was performed in three patients. No postoperative complications were noted. The mean follow-up period was 95 months. The 5-year overall survival was 87.5% and the 5-year recurrence-free survival was 75%. To date, there have been no local recurrences but two patients had lymph node recurrences. Seven patients are disease-free and one is deceased.

300IR 5-Grass pollen sublingual tablet offers relief from nasal symptoms in patients with allergic rhinitis.

BACKGROUND: 300IR 5-grass pollen sublingual immunotherapy tablets have been approved for the treatment of allergic rhinitis (AR) with or without conjunctivitis in adults and children >5 years with grass pollen allergy. This study was designed to review data on nasal symptoms with 300IR 5-grass pollen sublingual tablets in adults and children. METHODS: We reviewed data from four double-blind, placebo-controlled, randomized clinical trials. Two groups of patients who received a daily dose of either placebo or 300IR 5-grass pollen sublingual tablets starting 4 months before the expected start of the pollen season and continuing through the season were compared (analysis of covariance) for scores of sneezing, rhinorrhea, nasal pruritus, nasal congestion, total nasal symptom score (TNSS), and adult Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores. RESULTS: Data for 266 children (one pediatric trial) and 1036 adults (three trials) were analyzed. Compared with the placebo groups, mean TNSS in the 300IR groups was lower by 22% in children and 19-36% in adults. Among the four nasal symptoms, the lowest scores relative to placebo were for nasal congestion in children (31%) and adults (43%). Mean adult RQLQ scores were 21-31% lower in the 300IR group than in the placebo group. CONCLUSION: Allergen immunotherapy with 300IR 5-grass pollen sublingual tablets was consistently associated with AR symptom relief in adults and children and provided a clinically meaningful improvement in quality of life.