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Protontherapy to maintain local control of head and neck paragangliomas

Inflammatory labyrinthitis is defined as a fluctuant vestibulo-cochlear syndrome associated with an impairment of the blood-labyrinthine barrier (BLB) on delayed FLAIR MRI sequences. Systemic and intratympanic corticosteroids are the gold standard treatment but their effect is frequently insufficient. The objective is here to determine whether infliximab could be of value in the treatment of bilateral inflammatory labyrinthitis. A retrospective monocentric study was conducted between January 2013 and December 2021. All patients included in the study were affected with a bilateral vestibulo-cochlear syndrome associated with bilateral blood-labyrinthine barrier impairment. Patients were administered infliximab at the dose of 5 mg/kg every 6 weeks for 6 months. Audiometry, MRI with delayed FLAIR sequences on the labyrinth, and corticosteroid doses still required were assessed both before and after treatment with infliximab was completed. Pure-tone average (PTA) was the primary outcome. The secondary outcomes were the speech recognition threshold (SRT), the Dizziness Handicap Inventory (DHI) score, and the corticosteroid (CS) dose. A total of nine patients including five men and four women were enrolled in the study. Thirteen ears were analyzed. After a 6-month period of treatment, the mean PTA (54 ± 24 db versus 66 ± 22 db; p = 0.027), SRT (54 ± 37 db versus 66 ± 32 db; p = 0.041) and DHI score (27 ± 15 versus 9 ± 2; p = 0.032) significantly improved. After the 6-month treatment period, the mean CS dose decreased from 38 ± 33 to 6 ± 5 mg/day (p = 0.003). We conclude that infliximab substantially improves the vestibulo-cochlear function in patients with bilateral inflammatory labyrinthitis and could be of value in corticosteroid-dependent cases.

HeadNeck Paragangliomas have been historically relying on surgery mostly, with worsened quality of life and major sequelae. Conventional external radiation therapy seems to offer an equivalent control rate with a low toxicity profile. The aim of this study was to assess the safety and efficiency of intensity-modulated radiation therapy in HeadNeck paragangliomas.This is a retrospective monocentric study conducted in a referral center, including all patients treated with IMRT, whether as an exclusive or post-operative treatment for a tympanic and jugular, carotid, or vagal paraganglioma. Data collection was performed through the manuscript and computerized medical files, including consultation, operative, imaging, pathological analyses, delineation, and treatment planning reports. Success was defined as the complete or partial regression or stabilization without progression, or relapse in accordance with the RECIST criteria. Acute toxicities and long-term sequelae were assessed.Our cohort included 39 patients included between 2011 and 2021: 18 patients treated for a TJ PG (45.9%), 11 patients for a carotid PG (28.4%), and 9 for a vagal PG (23.1%). Twenty-nine patients had IMRT as an exclusive treatment (74.4%), whereas 10 patients had a post-operative complementary treatment (25.6%). Median follow-up in our cohort was 2318 days (average = 2200 days, 237-5690, sd = 1281.9). Among 39 patients, 37 were successfully controlled with IMRT (94.8%), and the toxicity profile was low without any major toxicity.IMRT seems an ideal treatment, whether exclusive or post-operative for HeadNeck paragangliomas.3 Laryngoscope, 2022.

Branchial cyst of the second pouch is the most common lesion of the nasopharyngeal lateral wall, generally localized between the pharyngeal wall and internal carotid artery. Cases consistent with such lesion, were collected. Symptomatic patients were treated with endoscopic trans-nasal marsupialisation, asymptomatic cases were followed-up. Among the 10 patients included, 4 were symptomatic and accordingly treated. In the literature, 36 cases were found, all of which were treated, most commonly with a total excision. Considering the benign nature of branchial nasopharyngeal cyst, its treatment should be tailored to each patient: endoscopic marsupialization in symptomatic lesion, follow-up in asymptomatic one. Laryngoscope, 132:1904-1908, 2022.

Germline mutations in genes encoding succinate dehydrogenase (SDH) are frequently involved in pheochromocytoma/paraganglioma (PPGL) development and were implicated in patients with the ‘3PAs’ syndrome (associating pituitary adenoma (PA) and PPGL) or isolated PA. However, the causality link between SDHx mutation and PA remains difficult to establish, and in vivo tools for detecting hallmarks of SDH deficiency are scarce. Proton magnetic resonance spectroscopy (1H-MRS) can detect succinate in vivo as a biomarker of SDHx mutations in PGL. The objective of this study was to demonstrate the causality link between PA and SDH deficiency in vivo using 1H-MRS as a novel noninvasive tool for succinate detection in PA. Three SDHx-mutated patients suffering from a PPGL and a macroprolactinoma and one patient with an apparently sporadic non-functioning pituitary macroadenoma underwent MRI examination at 3 T. An optimized 1H-MRS semi-LASER sequence (TR = 2500 ms, TE = 144 ms) was employed for the detection of succinate in vivo. Succinate and choline-containing compounds were identified in the MR spectra as single resonances at 2.44 and 3.2 ppm, respectively. Choline compounds were detected in all the tumors (three PGL and four PAs), while a succinate peak was only observed in the three macroprolactinomas and the three PGL of SDHx-mutated patients, demonstrating SDH deficiency in these tumors. In conclusion, the detection of succinate by 1H-MRS as a hallmark of SDH deficiency in vivo is feasible in PA, laying the groundwork for a better understanding of the biological link between SDHx mutations and the development of these tumors.

OBJECTIVE Chordomas represent one of the most challenging subsets of skull base and craniovertebral junction (CVJ) tumors to treat. Despite extensive resection followed by proton-beam radiation therapy, the recurrence rate remains high, highlighting the importance of developing efficient treatment strategies. In this study, the authors present their experience in treating clival and CVJ chordomas over a 29-year period. METHODS The authors conducted a retrospective study of clival and CVJ chordomas that were surgically treated at their institution from 1991 to 2020. This study focuses on three aspects of the management of these tumors: the factors influencing the extent of resection (EOR), the predictors of survival, and the outcomes of the endoscopic endonasal approaches (EEAs) compared with open approaches (OAs). RESULTS A total of 265 surgical procedures were performed in 210 patients, including 123 OAs (46.4%) and 142 EEAs (53.6%). Tumors that had an intradural extension (p = 0.03), brainstem contact (p = 0.005), cavernous sinus extension (p = 0.004), major artery encasement (p = 0.01), petrous apex extension (p = 0.003), or high volume (p = 0.0003) were significantly associated with a lower EOR. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 52.1% and 75.1%, respectively. Gross-total resection and Ki-67 labeling index < 6% were considered to be independent prognostic factors of longer PFS (p = 0.0005 and p = 0.003, respectively) and OS (p = 0.02 and p = 0.03, respectively). Postoperative radiation therapy correlated independently with a longer PFS (p = 0.006). Previous surgical treatment was associated with a lower EOR (p = 0.01) and a higher rate of CSF leakage after EEAs (p = 0.02) but did not have significantly lower PFS and OS compared with primary surgery. Previously radiation therapy correlated with a worse outcome, with lower PFS and OS (p = 0.001 and p = 0.007, respectively). EEAs were more frequently used in patients with upper and middle clival tumors (p = 0.002 and p < 0.0001, respectively), had a better rate of EOR (p = 0.003), and had a lower risk of de novo neurological deficit (p < 0.0001) compared with OAs. The overall rate of postoperative CSF leakage after EEAs was 14.8%. CONCLUSIONS This large study showed that gross-total resection should be attempted in a multidisciplinary skull base center before providing radiation therapy. EEAs should be considered as the gold-standard approach for upper/middle clival lesions based on the satisfactory surgical outcome, but OAs remain important tools for large complex chordomas.

Approximately 20% of patients diagnosed with a phaeochromocytoma or paraganglioma carry a germline mutation in one of the succinate dehydrogenase (SDHx) genes (SDHA, SDHB, SDHC and SDHD), which encode the four subunits of the SDH enzyme. When a pathogenic SDHx mutation is identified in an affected patient, genetic counselling is proposed for first-degree relatives. Optimal initial evaluation and follow-up of people who are asymptomatic but might carry SDHx mutations have not yet been agreed. Thus, we established an international consensus algorithm of clinical, biochemical and imaging screening at diagnosis and during surveillance for both adults and children. An international panel of 29 experts from 12 countries was assembled, and the Delphi method was used to reach a consensus on 41 statements. This Consensus Statement covers a range of topics, including age of first genetic testing, appropriate biochemical and imaging tests for initial tumour screening and follow-up, screening for rare SDHx-related tumours and management of elderly people who have an SDHx mutation. This Consensus Statement focuses on the management of asymptomatic SDHx mutation carriers and provides clinicians with much-needed guidance. The standardization of practice will enable prospective studies in the near future.

Objective: Petrous apex cholesterol granuloma (PACG) is a lesion that can give rise to different symptoms, and correlations with etiopathology are ambiguous. The aim of this study is to analyze the association between PACG symptoms and radiological findings at presentation, in order to establish a reproduceable pre-operative radiological evaluation and guide the surgical indication. Methods: PACG patients were collected in two tertiary care hospitals. All cases underwent CT/MRI to evaluate the cyst localization and erosion of surrounding structures. Typical and atypical symptoms were then analyzed and compared to radiologic findings established in accordance with the literature. Results: Twenty-nine patients were recruited; the most common symptoms were headache (69%), diplopia (20.7%) and fainting (24.1%), an atypical clinical manifestation related to jugular tubercle involvement. Significant associations between symptoms and radiologic findings were noted in terms of headache and temporal lobe compression (p = 0.04), fainting and jugular tubercle erosion (p < 0.001), vestibular symptoms and internal auditory canal erosion (p = 0.02), facial paresthesia and Meckel’s cave compression (p = 0.03), diplopia and Dorello canal involvement (p = 0.001), and tinnitus and cochlear basal turn erosion (p < 0.001). All patients were treated via an endoscopic–endonasal approach, in which extension was tailored to each case. At a median follow-up of 46 months, 93.1% of patients experienced resolution of symptoms. Conclusions: This clinico-radiological series demonstrates associations between symptoms and anatomical subsites involved with PACG. Hence, it may guide the surgeon at the time of surgical decision, since it asserts that typical and atypical symptoms are actually related to PACG.

Unilateral vestibular atelectasis (UVA), an entity first described by Merchant and Schuknecht in 1988, has rarely been reported in vivo as of yet. We specify here the clinical characteristics of 22 patients diagnosed with UVA. Patients with a radiological diagnosis of UVA who underwent delayed inner ear MRI were included between April 2017 and January 2020. Full clinical testing including ocular infrared video-oculography, oVEMPs, cVEMPs, vHIT, bithermal caloric testing and auditory testing was performed. There were 13 men and 9 women, of mean age 58.6 ± 13.7 years. Onset was more frequently sudden (73%) than insidious (27%) though both clinical presentations were reported, and positional vertigo was described in 41% of cases. There were only two (9%) patients reporting Tullio’s phenomenon. Vestibular testing showed that in 90% of cases, there was utricular dysfunction on oVEMP, while in 77% of cases, saccular function was preserved on cVEMP. vHIT showed high-velocity canal function impairment in all 22 patients: 8 patients (36%) had one impaired canal, 5 (23%) had two and 9 (41%) had all three canals affected. Caloric tests found complete unilateral areflexia, in 65% of tested cases, and partial deficiency in 35% of cases. Nine patients (40%) displayed asymmetrical hearing. We described in this study the various clinical presentations of a disease rarely reported in vivo, UVA. Initial clinical presentation can appear similar to an acute vestibular deficit, a recurrent positional vertigo, or fluctuating dizziness.

Patients with superior semicircular canal dehiscence syndrome, which can only be treated by surgery, present cochleo-vestibular symptoms related to a third-mobile window but also endolymphatic hydrops. Since cVEMP and oVEMP are disturbed by the presence of the dehiscence, the aim of the study is to assess the value of MRI for the diagnosis of endolymphatic hydrops in patients with superior semicircular canal dehiscence syndrome in comparison with cVEMP and oVEMP. In this retrospective cohort study we enrolled 33 ears in 24 patients with superior semicircular dehiscence syndrome who underwent a 4-h delayed intravenous Gd-enhanced 3D-FLAIR MRI and pure tone audiometry, cVEMP and oVEMP. For each patient MRI images were evaluated by two radiologists who used a compartmental endolymphatic hydrops grading system in comparison with cVEMP and oVEMP. Endolymphatic hydrops was found on MRI in 9 out of 33 SCDS ears (27.3%). We found no significant correlation between the presence of endolymphatic hydrops on MRI and cVEMP and oVEMP (p = 0.36 and p = 0.7, respectively). However, there was a significant correlation between the presence of endolymphatic hydrops on MRI and the degree of sensorineural hearing loss, Air Conduction-Pure Tone Average level (p = 0.012) and Bone Conduction-Pure Tone Average level (p = 0.09), respectively. We demonstrated that EH might be observed in 27.3% of superior semicircular dehiscence syndrome ears. The role of inner ear MRI is important to detect endolymphatic hydrops, since cVEMP and oVEMP are disturbed by the presence of the dehiscence, because these patients could benefit from a medical treatment. Level 3.

BACKGROUND A significant proportion of spontaneous cerebrospinal fluid (sCSF) leaks are associated with idiopathic intracranial hypertension (IIH). The aim of this study was to assess the association between sCSF rhinorrhea and transverse venous sinus stenosis (VSS), a feature commonly observed in IIH with a proposed role in its pathophysiology. METHODS In this single-center, retrospective, matched case-control study, venous and pituitary imaging data of consecutive patients undergoing endoscopic surgery for sCSF rhinorrhea over the last 10 years were retrospectively reviewed. Measurement of the height of the pituitary gland was used to assess empty sella and VSS was quantified as the ratio between the minimal area of the transverse sinus and the cross-sectional area of the sigmoid sinus. VSS was considered significant when it was ≥50% and bilateral. Cases were compared with 1:1 age- and sex-adjusted controls explored for causes other than IIH, intracranial mass effect, or venous thrombosis. RESULTS Twenty-nine patients were included (median age 56 years, females 69%, body mass index [BMI] 33.8 kg/m2 ). Cases had a significantly lower height of the pituitary gland than controls (2.5 mm vs 6.6 mm, p < 0.001). Bilateral VSS was found in 23 of 29 cases (79%; 95% confidence interval [CI], 65% to 94%) vs 3 of 29 controls (10%; 95% CI, 0% to 21%), with p < 0.001. CONCLUSION In this retrospective study, sCSF leaks were strongly associated with VSS. This novel finding provides a rationale for further investigation of the role of VSS in the onset of sCSF leaks and of the potential interest in venous stenting after the surgical repair of leaks.

(1) Background: In head and neck squamous cell carcinoma, tumor hypoxia has been associated with radio/chemoresistance and poor prognosis, whereas human papillomavirus (HPV)-positive status has a positive impact on treatment response and survival outcomes. The aim of this study was to evaluate the expression and the potential prognostic value of hypoxia-induced endogenous markers in patients treated for squamous cell carcinoma of the nasal cavity and paranasal sinuses (SNSCC), and their correlation with HPV status. (2) Methods: In this monocentric study, patients treated in a curative intent for a SNSCC were screened retrospectively. Protein expression of CA-IX, GLUT-1, VEGF, VEGF-R1, and HIF-1α was determined by immunohistochemical staining, scored, and then correlated with overall survival (OS) and locoregional recurrence free survival (LRRFS). HPV status was assessed and correlated with hypoxic markers. (3) Results: 40 patients were included. A strong expression of CA-IX, GLUT-1, VEGF, and VEGF-R1 was detected in 30%, 32.5%, 50%, and 37.5% of cases, respectively. HIF-1α was detected in 27.5% of cases. High CA-IX expression was associated in univariate analysis with poor OS (p = 0.035), but there was no significant association between GLUT-1, VEGF, VEGF-R1, and HIF-1α expression, and OS/LRRFS. There was no correlation found between HPV status and hypoxia-induced endogenous markers (all p > 0.05). (4) Conclusions: This study provides data on the expression of hypoxia-induced endogenous markers in patients treated for SNSCC and underlines the potential role of CA-IX as a prognostic biomarker for SNSCC.

Bilateral vestibulopathy (BV) is an uncommon disorder and the etiology remained idiopathic in most cases. Delayed 3D-FLAIR sequences have provided new insights into various inner ear diseases, allowing the evaluation of the endolymphatic space and the permeability of the blood–labyrinthine barrier (BLB). The aim of this study was to assess both the morphology of the endolymphatic space and the permeability of the BLB in patients with BV as evaluated by delayed 3D-FLAIR sequences. In this retrospective study, we performed 3D-FLAIR sequences 4 h after administering contrast media to 42 patients with BV. Two radiologists independently evaluated the morphology of the endolymphatic space (either vestibular atelectasis or endolymphatic hydrops) and the permeability of the BLB. Morphologic anomalies of the endolymphatic space and vestibular blood–labyrinthine barrier impairment were observed in 59.6% of patients with BV. Bilateral vestibular atelectasis (VA) was found in 21 patients (50%), involving only the utricle and all three ampullas while the saccule was always observed with no sign of collapse: idiopathic BV (n = 19), aminoglycoside administration (n = 1) and few days following abdominal surgery (n = 1). One patient had bilateral vestibular malformation. BLB impairment was observed in five patients (11.9%): paraneoplastic (n = 1), lymphoma (n = 1), autoimmune (n = 1), and vestibular “neuritis” (n = 2). Seventeen patients (40.4%) had normal MRI with no endolymphatic space anomaly or BLB impairment. Patients with BV presented with morphologic anomalies of the endolymphatic space or BLB impairment in 59.6% of patients.

Olfactory neuroblastomas (ONBs) are rare malignant tumours that arise in the nasal vault. To date, the Hyams grade remains the only widely used histological grading system. However, it is based only on morphological criteria, and has not been updated since 1988. The objective of this study was to explore the prognostic potential of the Ki67 proliferation index (PI) and tumour-infiltrating lymphocytes (TILs) in ONB.A retrospective study was conducted on a bicentric series of 45 cases. The Ki67 PI was determined by counting at least 1000 nuclei on whole slides. TILs were evaluated with CD20, CD4 and CD8 immunohistochemical markers on whole slides. In this series, Hyams grades I, II, III and IV accounted for 13.4%, 44.4%, 20% and 22.2% of all cases, respectively. The Ki67 PI ranged from 1 to 93; the Ki67 PI was significantly higher in Hyams grade III-IV ONBs than in Hyams grade I-II ONBs (P 0.0001). A Ki67 PI of ≥25 was associated with poorer survival (P = 0.02). TILs were present in both stromal and intratumoral compartments, but were located predominantly in the stromal component of the tumour. The numbers of intratumoral CD8+ cells/mmOur findings suggest that the Ki67 PI and TILs could be used as prognostic markers, as a potential alternative to the Hyams grade.

The fungal pathogen Candida albicans frequently forms drug-resistant biofilms in hospital settings and in chronic disease patients. Cell adhesion and biofilm formation involve a family of cell surface Als (agglutinin-like sequence) proteins. It is now well documented that amyloid-like clusters of laterally arranged Als proteins activate cell-cell adhesion under mechanical stress, but whether amyloid-like bonds form between aggregating cells is not known. To address this issue, we measure the forces driving Als5-mediated intercellular adhesion using an innovative fluidic force microscopy platform. Strong cell-cell adhesion is dependent on expression of amyloid-forming Als5 at high cell surface density and is inhibited by a short antiamyloid peptide. Furthermore, there is greatly attenuated binding between cells expressing amyloid-forming Als5 and cells with a nonamyloid form of Als5. Thus, homophilic bonding between Als5 proteins on adhering cells is the major mode of fungal aggregation, rather than protein-ligand interactions. These results point to a model whereby amyloid-like β-sheet interactions play a dual role in cell-cell adhesion, that is, in formation of adhesin nanoclusters ( cis-interactions) and in homophilic bonding between amyloid sequences on opposing cells ( trans-interactions). Because potential amyloid-forming sequences are found in many microbial adhesins, we speculate that this novel mechanism of amyloid-based homophilic adhesion might be widespread and could represent an interesting target for treating biofilm-associated infections.

The ongoing COVID-19 pandemic, caused by SARS-CoV-2, constitutes a tremendous global health issue. Continuous monitoring of the virus has become a cornerstone to make rational decisions on implementing societal and sanitary measures to curtail the virus spread. Additionally, emerging SARS-CoV-2 variants have increased the need for genomic surveillance to detect particular strains because of their potentially increased transmissibility, pathogenicity and immune escape. Targeted SARS-CoV-2 sequencing of wastewater has been explored as an epidemiological surveillance method for the competent authorities. Few quality criteria are however available when sequencing wastewater samples, and those available typically only pertain to constructing the consensus genome sequence. Multiple variants circulating in the population can however be simultaneously present in wastewater samples. The performance, including detection and quantification of low-abundant variants, of whole genome sequencing (WGS) of SARS-CoV-2 in wastewater samples remains largely unknown. Here, we evaluated the detection and quantification of mutations present at low abundances using the SARS-CoV-2 lineage B.1.1.7 (alpha variant) defining mutations as a case study. Real sequencing data were in silico modified by introducing mutations of interest into raw wild-type sequencing data, or by mixing wild-type and mutant raw sequencing data, to mimic wastewater samples subjected to WGS using a tiling amplicon-based targeted metagenomics approach and Illumina sequencing. As anticipated, higher variation, lower sensitivity and more false negatives, were observed at lower coverages and allelic frequencies. We found that detection of all low-frequency variants at an abundance of 10%, 5%, 3% and 1%, requires at least a sequencing coverage of 250X, 500X, 1500X and 10,000X, respectively. Although increasing variability of estimated allelic frequencies at decreasing coverages and lower allelic frequencies was observed, its impact on reliable quantification was limited. This study provides a highly sensitive low-frequency variant detection approach, which is publicly available at https://galaxy.sciensano.be, and specific recommendations for minimum sequencing coverages to detect clade-defining mutations at specific allelic frequencies.

Simple Summary Sinonasal cancers are rare. Surgery is often the first step of the therapeutic strategy, possibly complemented by adjuvant therapies. Surgical excision can be performed by an open approach with external incision, by an endoscopic approach using the nasal fossa as a surgical corridor, or by a combination of both. This article describes the main surgical techniques that can be used for the management of sinonasal cancer and reviews the criteria that lead to the choice of one technique over another. Abstract Surgery plays an important role in the treatment of sinonasal cancer. Many surgical approaches have been described, including open, endoscopic, or combined approaches. The choice is based on several criteria: general criteria related to the oncological results and morbidity of each technique, specific criteria related to the tumor (tumor extensions, tumor pathology), the patient, or the surgeon himself. The aims of this review are (i) to provide a complete overview of the surgical techniques available for the management of sinonasal malignant tumors, with a special focus on recent developments in the field of transnasal endoscopic surgery; (ii) to summarize the criteria that lead to the choice of one technique over another. In particular, the oncological outcomes, the morbidity of the different techniques, and the specificities of each histologic subtype will be discussed based on a comprehensive literature review.

The worldwide emergence and spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) since 2019 has highlighted the importance of rapid and reliable diagnostic testing to prevent and control the viral transmission. The monitoring of the viral spread can be performed using individual diagnostics in clinical samples and global detection of SARS-CoV-2 in wastewater samples. Reverse-transcription droplet digital PCR (RT-ddPCR) offers an attractive platform for absolute RNA quantification in comparison to the gold standard reverse transcription quantitative PCR (RT-qPCR) that only yields relative quantification results. To avoid inaccurate results due to false negatives caused by polymorphisms or point mutations that can possibly compromise the accuracy of the diagnostic tests, a multiplex RT-ddPCR method was developed by combining previously published SARS-CoV-2 detection RT-qPCR assays targeting well-conserved ORF1a and RdRp genes. These assays were successfully evaluated in silico for their inclusivity using GISAID sequences from the beginning of November 2020 to the end of February 2021. The sensitivity and specificity of the new RT-ddPCR method was evaluated and its applicability on both clinical and wastewater samples was illustrated. In conclusion, a reliable and sensitive multiplex one-step RT-ddPCR assay for reliable quantification of SARS-CoV-2 RNA in clinical and wastewater samples was developed and assessed, providing a key tool for the current health crisis.

Background Management of idiopathic intracranial hypertension (IIH) is recommended after surgical repair of spontaneous cerebrospinal fluid leaks (sCSF-leaks) of the skull base for prevention of recurrence. Purpose To assess the feasibility of venous sinus stenting, a treatment commonly used for the treatment of IIH associated with intracranial venous sinus stenosis (VSS), after sCSF-leaks closure. Materials and methods A single-center cohort series of consecutive patients who underwent sCSF-leak closure was retrospectively analyzed. Stenting was considered either for leak recurrence or in prophylactic manner after repair in patients with VSS as confirmed by cerebral venous imaging. Leak recurrence, need for new repair or adjunctive treatment of IIH, meningitis, and stenting complications were determined at the last follow-up. Cases who had prophylactic stenting were compared to historical controls before stenting option. Results Twenty-two patients had intracranial venous stenting after sCSF-leak closure. Their median age was 58 years (Q1=45; Q3=68), BMI=31 kg.m−2 (Q1=27; Q3=36), and female rate=85%. The overall rate of successful repair after stenting was 95% (95% CI = 87–100%) at a median follow-up of 2.4 years (Q1=1.2; Q3=3.3). Adjunctive treatment for IIH was needed in 4 patients (4/22, 18%) including 2 patients without leak recurrence. No meningitis, permanent morbidity or mortality was observed after stenting. Compared to 18 controls, cases had significantly less recurrence (P = 0.03), and a trend for less adjunctive treatment for IIH (P = 0.06). Conclusions Our study suggests that stenting might be a valid option for prevention of sCSF-leak recurrences after repair in patients with intracranial venous sinus stenosis.

For 1 year now, the world is undergoing a coronavirus disease-2019 (COVID-19) pandemic due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The most widely used method for COVID-19 diagnosis is the detection of viral RNA by RT-qPCR with a specific set of primers and probe. It is important to frequently evaluate the performance of these tests and this can be done first by an in silico approach. Previously, we reported some mismatches between the oligonucleotides of publicly available RT-qPCR assays and SARS-CoV-2 genomes collected from GISAID and NCBI, potentially impacting proper detection of the virus. In the present study, 11 primers and probe sets investigated during the first study were evaluated again with 84,305 new SARS-CoV-2 unique genomes collected between June 2020 and January 2021. The lower inclusivity of the China CDC assay targeting the gene N has continued to decrease with new mismatches detected, whereas the other evaluated assays kept their inclusivity above 99%. Additionally, some mutations specific to new SARS-CoV-2 variants of concern were found to be located in oligonucleotide annealing sites. This might impact the strategy to be considered for future SARS-CoV-2 testing. Given the potential threat of the new variants, it is crucial to assess if they can still be correctly targeted by the primers and probes of the RT-qPCR assays. Our study highlights that considering the evolution of the virus and the emergence of new variants, an in silico (re-)evaluation should be performed on a regular basis. Ideally, this should be done for all the RT-qPCR assays employed for SARS-CoV-2 detection, including also commercial tests, although the primer and probe sequences used in these kits are rarely disclosed, which impedes independent performance evaluation.

Objective To describe the outcome and feasibility of an exclusive endoscopic transcanal transpromontorial approach (ETTA) for decompression of the labyrinthine segment of the facial nerve (LSFN). Patient A 60-year-old man with a left-sided transverse fracture of temporal bone involving the LSFN, resulting in a grade VI House-Brackmann (HB) facial palsy, associated with ipsilateral total sensorineural hearing loss. Intervention Surgical decompression of the LSFN by ETTA. Main outcome measure The patient underwent ETTA which allowed complete exposure and decompression of the LSFN. Results One year postoperatively, the patient had recovered with House-Brackmann grade II facial function. Conclusion ETTA can be considered a valuable and appropriate technique for posttraumatic decompression of LSFN, associated with unilateral total sensorineural hearing loss. The procedure resulted in significant facial nerve function improvement. ETTA should be considered both a scarless, mastoid conserving and less invasive surgical technique for posttraumatic LSFN decompression associated with pre-existing cochlear impairment.

BACKGROUND The spheno-orbital region (SOR) is a complex anatomic area that can be accessed with different surgical approaches. OBJECTIVE To quantitatively compare, in a preclinical setting, microsurgical transcranial approaches (MTAs), endoscopic endonasal transpterygoid approach (EEA), and endoscopic transorbital approaches (ETOAs) to the SOR. METHODS These approaches were performed in 5 specimens: EEA, ETOAs (superior eyelid and inferolateral), anterolateral MTAs (supraorbital, minipterional, pterional, pterional-transzygomatic, and frontotemporal-orbitozygomatic), and lateral MTAs (subtemporal and subtemporal transzygomatic). All specimens underwent high-resolution computed tomography; an optic neuronavigation system with dedicated software was used to quantify working volume and exposed area for each approach. Mixed linear models with random intercepts were used for statistical analyses. RESULTS Anterolateral MTAs offer a direct route to the greater wings (GWs) and lesser wings (LWs); only they guarantee exposure of the anterior clinoid. Lateral MTAs provide access to a large area corresponding to the GW, up to the superior orbital fissure (SOF) anteriorly and the foramen rotundum medially. ETOAs also access the GW, close to the lateral portion of SOF, but with a different angle of view as compared to lateral MTAs. Access to deep and medial structures, such as the lamina papyracea and the medial SOF, is offered only by EEA, which exposes the LW and GW only to a limited extent. CONCLUSION This is the first study that offers a quantitative comparison of the most used approaches to SOR. A detailed knowledge of their advantages and limitations is paramount to choose the ideal one, or their combination, in the clinical setting.

International audience

International audience; Background: To describe the characteristics of the largest European study of MEC of salivary glands and to determine the prognostic factors for overall and disease free survival.Patients and methods: Patients with MEC were prospectively included in the Réseau d'Expertise Français sur les Cancers ORL Rares (REFCOR, French Network of Rare Head and Neck Tumors) database between 2009 and 2015.Results: A total of 292 patients were included. Tumors were classified as low grade in 175 cases (60%), intermediate in 39 (13%) and high grade in 78 (27%). Median follow-up was 26 months. The 5-year OS and DFS rates were respectively 83% and 69%. In multivariate analysis, age (p = 0.004), diabetes (p = 0.02) and advanced stage (p = 0.03) were found to have a significant negative impact on OS. Diabetes (p = 0.001), alcohol consumption (p = 0.003) and advanced stage (p = 0.001) were found to have a significant negative impact on DFS. Compare to low grade, high grade tended to have a negative impact on OS (p = 0.05) and had a significant effect on DFS (0.002) while intermediate grade had no significant influence on survival. The surgical treatment had a positive impact on both OS (p = 0.00005) and DFS (p = 0.0005). Postoperative radiotherapy had no impact in multivariate analysis.Conclusion: Advanced clinical stage, high grade tumor, high age, the impossibility of carrying out a complete surgical resection, and diabetes are the main prognostic factors in this prospective series of patients with MEC. Such findings open new research perspectives on the influence of these components on initial patient care.

Background The association between spontaneous cerebrospinal fluid (CSF) leak/rhinorrhea and idiopathic intracranial hypertension (IIH) has been increasingly recognized over the last years. However, considerable variability of opinion regarding the assessment, investigations, and management of patients with spontaneous CSF rhinorrhea remains. Methods A consensus group was formed from experts from Europe, Asia, Australia, South and North America. Following literature review and open discussions with members of the panel, a set of 61 statements was produced. A modified Delphi method was used to refine expert opinion with 3 rounds of questionnaires and a consensus group meeting in Santo-Rhino meeting in September 2019. Results Fifty statements (82% of total) on spontaneous CSF leak and IIH reached consensus. In 38 of 50 statements, the median response was 7 (strongly agree) and in the 12 remaining statements the median response was 6 (agree). Eleven statements were excluded because they did not reach consensus and one new statement was added during SantoRhino meeting. The final statements refer to patient history and clinical examination ("History taking should include presence of headache, tinnitus and visual defects"), investigations (role of Thin Slice Computed Tomography and CISS/FLAIR sequences in Magnetic Resonance Imaging), principles of management (watchful waiting or measures to reduce ICP are supplementary but cannot subsitute surgical closure), surgical technique, intraoperative, early postoperative and long term management. Conclusion We present fifty consensus statements on the diagnosis, investigation, and management of spontaneous CSF rhinorrhea based on the currently available evidence and expert opinion. Although by no means comprehensive and final, we believe they can contribute to the standardization of clinical practice. Early diagnosis, prompt surgical closure of the defect, assesment for and treatment of potentially co-existing idiopathic intracranial hypertension in a comprehensive multidisciplinary approach are essential in order to successfully manage spontaneous CSF rhinorrhea, reduce associated morbidity and prevent recurrence.

International audience; Scedosporiosis/lomentosporiosis is a devastating emerging fungal infection. Our objective was to describe the clinical pattern and to analyze whether taxonomic grouping of the species involved was supported by differences in terms of clinical presentations or outcomes. We retrospectively studied cases of invasive scedosporiosis in France from 2005 through 2017 based on isolates characterized by polyphasic approach. We recorded 90 cases, mainly related to Scedosporium apiospermum (n = 48), S. boydii/S. ellipsoideum (n = 20), and Lomentospora prolificans (n = 14). One-third of infections were disseminated, with unexpectedly high rates of cerebral (41%) and cardiovascular (31%) involvement. In light of recent Scedosporium taxonomic revisions, we aimed to study the clinical significance of Scedosporium species identification and report for the first time contrasting clinical presentations between infections caused S. apiospermum, which were associated with malignancies and cutaneous involvement in disseminated infections, and infections caused by S. boydii, which were associated with solid organ transplantation, cerebral infections, fungemia, and early death. The clinical presentation of L. prolificans also differed from that of other species, involving more neutropenic patients, breakthrough infections, fungemia, and disseminated infections. Neutropenia, dissemination, and lack of antifungal prescription were all associated with 3-month mortality. Our data support the distinction between S. apiospermum and S. boydii and between L. prolificans and Scedosporium sp. Our results also underline the importance of the workup to assess dissemination, including cardiovascular system and brain. Lay Summary Scedosporiosis/lomentosporiosis is a devastating emerging fungal infection. Our objective was to describe the clinical pattern and to analyze whether taxonomic grouping of the species involved was supported by differences in terms of clinical presentations or outcomes.