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Objectives: To describe primary Sjögren's disease (SjD) patients presenting no or low level of dryness and to compare them with SjD patients with oral or ocular dryness features., Methods: All patients diagnosed with SjD according to AECG or ACR/EULAR criteria in our tertiary reference centre were included. Patients with high or low subjective symptoms or objective signs of dryness were compared., Results: Overall, 509 patients were included for the comparison of patients with high (n=456) or low (n=53) level of subjective dryness and 472 for the comparison of patients with (n=359) or without (n=113) high objective dryness. Compared with patients with subjective dryness, patients without high subjective dryness were significantly younger (median 49 (39-62) years vs 58 (47-67) years, p<0.01), diagnosed earlier (median time from first symptoms to diagnosis 2 (0.5-4.5) years vs 4 (1-9.25), p=0.0056), more frequently anti-SSA positive ((83% vs 64%, p=0.008) and had less focal sialadenitis in minor salivary gland biopsy (69% vs 83%, p=0.02).The patients without high level of objective dryness (n=113) were also younger (51 (41-60) vs 58 (47-67) years, p<0.001) and were more frequently anti-SSA positive (79% vs 63%, p=0.002).In both groups, no difference was observed regarding disease activity., Conclusions: Among the patients with SjD, those without high subjective or objective dryness features had a younger profile, a faster diagnosis which may result from a more acute onset, were more frequently anti-SSA positive than patients with high dryness features., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Tinnitus is generally defined as an auditory perception in the absence of environmental sound stimulation. However, this definition is quite incomplete as it omits an essential aspect, the patient's point of view. This point of view constitutes, first and foremost, a global and unified lived experience, which is not only sensory (localization, loudness, pitch and tone), but also cognitive (thoughts, attentiveness, behaviors) and emotional (discomfort, suffering). This experience can be lived in a very unpleasant way and consequently have a very negative impact on quality of life. This article proposes and justifies a new definition for tinnitus elaborated by a group of French clinicians and researchers, which is more in line with its phenomenology. It also provides a minimum knowledge base, including possibilities for clinical care, hoping to eradicate all misinformation, misconceptions and inappropriate attitudes or practices toward this condition. Here is the short version of our definition: Tinnitus is an auditory sensation without an external sound stimulation or meaning, which can be lived as an unpleasant experience, possibly impacting quality of life., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Gitelman syndrome (GS) is a rare salt-losing tubulopathy caused by an inactivating mutation in the SLC12A3 gene, encoding the thiazide-sensitive sodium chloride cotransporter (NCC). Patients with GS frequently complain of vertigo, usually attributed to hypovolemia. Because NCC is also located in the endolymphatic sac, we hypothesized that patients with GS might have vestibular dysfunction. Between April 2013 and September 2016, 20 (22%) out of 90 patients followed at the reference center complained of vertigo in the absence of orthostatic hypotension. Sixteen of them were referred to an otology department for investigation of vestibular function. The vertigo was of short duration and triggered in half of them by head rotation. Seven patients (44%) had a vestibular syndrome. Vestibular syndrome was defined: (1) clinically, as nystagmus triggered by the head shaking test ( n = 5); and/or (2) paraclinically, as an abnormal video head impulse test ( n = 0), abnormal kinetic test ( n = 4) and/or abnormal bithermal caloric test ( n = 3). Five patients had associated auditory signs (tinnitus, aural fullness or hearing loss). In conclusion, we found a high frequency of vestibular disorder in GS patients suffering from vertigo, suggesting a role of NCC in the inner ear. Referent physicians of these patients should be aware of this extrarenal manifestation that requires specific investigations and treatment.

Purpose: We investigated the activities of an ImmunoTOX board, an academic, multidisciplinary group of oncologists and organ specialists that adopts a real-life, case-by-case approach in the management of patients with immune-related adverse events (irAEs)., Experimental Design: The ImmunoTOX assessment board was set up in 2016 at Gustave Roussy in France. It meets every 2 weeks to discuss the case-by-case management of patients presenting with irAEs. Here, we describe the ImmunoTOX board's activities between 2016 and 2019., Results: Over study period, 398 requests (concerning 356 patients) were submitted to the ImmunoTOX board. Most of the requests concerned the putative causal link between immunotherapy and the irAE (n = 148, 37%), followed by possible retreatment after temporary withdrawal because of an adverse event (n = 109, 27%), the clinical management of complex situations (n = 100, 25%) and the initiation of immunotherapy in patients with pre-existing comorbidities (n = 41, 10%). The ImmunoTOX board discerned 273 irAEs. The five organ systems most frequently involved by irAEs were lung (n = 58, 21%), gastrointestinal tract (n = 36, 13%), liver or biliary tract (n = 33, 12%), musculoskeletal system (n = 27, 10%), and nervous system (n = 23, 8%). The time to occurrence was shorter for severe irAEs (grade III and VI) than for mild irAEs (grades I and II), with medians of 47 and 91 days, respectively (p = 0.0216)., Conclusion: The main medical needs in the management of irAEs involved the lung organ. Severe irAEs were expected to occur earlier than mild irAEs. This real-life study can help to better estimate medical needs and therefore help to assess the management of irAEs., Competing Interests: Conflict of interest statement Pr Olivier Lambotte: Has received expert testimony and consultancy fees from BMS France, MSD, and Astra Zeneca, consultancy fees from Genzyme, and expert testimony fees from Janssen. Dr Jean-Marie Michot: Principal/sub-Investigator of Clinical Trials for: Abbvie, Aduro, Agios, Amgen, Argen-x, Astex, AstraZeneca, Aveo pharmaceuticals, Bayer, Beigene, Blueprint, BMS, Boeringer Ingelheim, Celgene, Chugai, Clovis, Daiichi Sankyo, Debiopharm, Eisai, Eos, Exelixis, Forma, Gamamabs, Genentech, Gortec, GSK, H3 biomedecine, Incyte, Innate Pharma, Janssen, Kura Oncology, Kyowa, Lilly, Loxo, Lysarc, Lytix Biopharma, Medimmune, Menarini, Merus, MSD, Nanobiotix, Nektar Therapeutics, Novartis, Octimet, Oncoethix, Oncopeptides AB, Orion, Pfizer, Pharmamar, Pierre Fabre, Roche, Sanofi, Servier, Sierra Oncology, Taiho, Takeda, Tesaro, Xencor. PERSONAL FEES (Monies paid to you for services rendered, generally honoraria, royalties or fees for consulting, lectures, speakers bureaus, expert testimony, employment, ad-boards, etc.): Roche, Celgene, Bristol-Myers Squibb, AstraZeneca, Janssen. Dr Aurélien Marabelle: Principal/sub-Investigator of Clinical Trials for: Abbvie, Aduro, Agios, Amgen, Argen-x, Astex, AstraZeneca, Aveo pharmaceuticals, Bayer, Beigene, Blueprint, BMS, Boeringer Ingelheim, Celgene, Chugai, Clovis, Daiichi Sankyo, Debiopharm, Eisai, Eos, Exelixis, Forma, Gamamabs, Genentech, Gortec, GSK, H3 biomedecine, Incyte, Innate Pharma, Janssen, Kura Oncology, Kyowa, Lilly, Loxo, Lysarc, Lytix Biopharma, Medimmune, Menarini, Merus, MSD, Nanobiotix, Nektar Therapeutics, Novartis, Octimet, Oncoethix, Oncopeptides AB, Orion, Pfizer, Pharmamar, Pierre Fabre, Roche, Sanofi, Servier, Sierra Oncology, Taiho, Takeda, Tesaro, Xencor. PERSONAL FEES (Monies paid to you for services rendered, generally honoraria, royalties or fees for consulting, lectures, speakers bureaus, expert testimony, employment, ad-boards, etc.): Medimmune, Pfizer, Servier, AstraZeneca, Janssen Bristol-Myers Squibb. Pr Christophe Massard: Principal/sub-Investigator of Clinical Trials for: Abbvie, Aduro, Agios, Amgen, Argen-x, Astex, AstraZeneca, Aveo pharmaceuticals, Bayer, Beigene, Blueprint, BMS, Boeringer Ingelheim, Celgene, Chugai, Clovis, Daiichi Sankyo, Debiopharm, Eisai, Eos, Exelixis, Forma, Lilly, Loxo, Lysarc, Lytix Biopharma, Medimmune, Menarini, Merus, MSD, Nanobiotix, Nektar Therapeutics, Novartis, Octimet, Oncoethix, Oncopeptides AB, Orion, Pfizer, Pharmamar, Pierre Fabre, Roche, Sanofi, Servier, Sierra Oncology, Taiho, Takeda, Tesaro, Xencor. PERSONAL FEES (Monies paid to you for services rendered, generally honoraria, royalties or fees for consulting, lectures, speakers bureaus, expert testimony, employment, ad-boards, etc.): Medimmune, Pfizer, AstraZeneca, Janssen, Bristol-Myers Squibb. Pr Jean-Charles Soria: From September 2017 to the end of 2019, Pr Soria was Senior Vice-President Research & Development Oncology at AstraZeneca in Gaithersburg, Maryland, United States. Pr Benjamin Besse: Sponsored research at Gustave Roussy Cancer CenterAbbvie, Amgen, AstraZeneca, Blueprint Medicines, BMS, Boehringer Ingelheim, Celgene, Cristal Therapeutics, Eli Lilly, GSK, Ignyta, IPSEN, Janssen, Merck KGaA, MSD, Nektar, Onxeo, OSE Immunopharmaceutics, Pfizer, Pharma Mar, Sanofi, Spectrum Pharmaceuticals, Takeda, Tiziana Pharma. Dr Stéphane Champiat: Principal/sub-Investigator of Clinical Trials for: Abbvie, Aduro, Agios, Amgen, Argen-x, Astex, AstraZeneca, Aveo pharmaceuticals, Bayer, Beigene, Blueprint, BMS, Boeringer Ingelheim, Celgene, Chugai, Clovis, Daiichi Sankyo, Debiopharm, Eisai, Eos, Exelixis, Forma, Lilly, Loxo, Lysarc, Lytix Biopharma, Medimmune, Menarini, Merus, MSD, Nanobiotix, Nektar Therapeutics, Novartis, Octimet, Oncoethix, Oncopeptides AB, Orion, Pfizer, Pharmamar, Pierre Fabre, Roche, Sanofi, Servier, Sierra Oncology, Taiho, Takeda, Tesaro, Xencor. PERSONAL FEES (Monies paid to you for services rendered, generally honoraria, royalties or fees for consulting, lectures, speakers bureaus, expert testimony, employment, ad-boards, etc.): Amgen. All other authors: no conflicts of interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The interrogation is essential to trace the genesis of the tinnitus and to appreciate its repercussion. Clinical examination should look for a local, vascular or cervical cause. The ENT consultation with audiogram and tinnitus evaluation is essential to know the characteristics of the tinnitus and to consider the treatment. If tinnitus is accompanied by a decrease in hearing, then wearing hearing aids can correct deafness and decrease the tinnitus. The psychological impact of tinnitus must always be taken into account and the use of a multidisciplinary team is an interesting solution. Medical treatments are not very effective; on the other hand psychotherapies (CBT, TRT and sophrology) bring a real improvement. The doctor's speech must always be supportive and provide therapeutic hope., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Objective: The relevance of the Th17 pathway in primary SS (pSS) is unclear. Published studies have relied on restimulating circulating CD161 + T cells in vitro for quantitation of IL-17-producing cells. While CD161 marks all IL-17 + T cells, it is also expressed by other Th subsets. The aim of this study was to directly analyse retinoic acid receptor-related orphan nuclear receptor (ROR)-γ expressing and non-expressing subsets of CD161 + T cells to determine the relevance of the Th17 pathway in pSS., Methods: We quantitated the frequencies of both CD161 - and RORγ-expressing T cells by comparative flow cytometry in peripheral blood mononuclear cells from a well-stratified cohort of pSS patients and control subjects. We also analysed the expression of antigen D-related HLA (HLA-DR) and CD161 in labial salivary glands from nine subjects undergoing a diagnostic biopsy., Results: While the frequencies of both RORγ + and RORγ - subsets of CD161 + CD4 + T cells were increased in peripheral blood from pSS patients, the increase in the RORγ + subset positively correlated with humoral manifestations of the disease (anti-SSA/SSB autoantibodies and hypergammaglobulinaemia), but not with disease activity, and vice versa for the RORγ - subset. An increased frequency of HLA-DR + CD161 + CD4 + T cells was observed in labial salivary gland biopsies from pSS patients, suggesting chronic activation of CD161 + CD4 + T cells in the target tissue of the disease., Conclusion: In addition to pointing to CD161 as a marker of a pathogenic subset of CD4 + T cells in pSS patients, our data indicate that even though the RORγ + (Th17) CD161 + subset might contribute to humoral manifestations of the disease, the RORγ - (non-Th17) CD161 + subset is the one associated with disease activity in pSS patients., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Mass cytometry has recently emerged as a promising tool for clinical research. However, few studies have demonstrated its benefit for patient stratification and biomarker identification. Primary Sjögren's syndrome (pSS) is a prototype of chronic autoimmune disease, the pathogenesis of which remains unclear and for which treatment does not exist., Objective: This observational case-control study was designed to discover new cellular biomarkers and therapeutic targets in patients with pSS., Methods: Forty-nine patients with pSS and 45 control subjects were enrolled for clinical evaluation and mass cytometry quantification of 34 protein markers in blood. For a third of these subjects, matched labial salivary gland biopsy specimens were also analyzed by mass cytometry and immunohistochemistry., Results: In salivary gland biopsy specimens from patients with pSS, we identified a high number of activated CD8(+) T cells, terminally differentiated plasma cells, and activated epithelial cells, pointing to new pathogenic mechanisms for future clinical intervention. In blood, we identified a 6-cell disease signature defined by decreased numbers of CD4 and memory B lymphocytes, decreased plasmacytoid dendritic cell numbers, and increased representation of activated CD4 and CD8 T cells and plasmablasts. These blood cellular components correlated with clinical parameters and, when taken together, clustered patients into subsets with distinct disease activity and glandular inflammation., Conclusion: This first application of mass cytometry to a well-stratified clinical cohort and small biopsy tissues establishes the benefits of such an approach for the discovery of new biomarkers and therapeutic targets. Similar high-dimensional immunophenotyping strategies could be implemented in longitudinal and interventional clinical settings in this and other disease areas., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

The usual treatments for primary snoring are uvulopalatopharyngoplasty (UPPPP) and laser assisted uvulopalatoplasty, their morbidity is known, particularly considerable postoperative pain. We have performed a prospective study on a population of 23 patients with primary snoring (respiratory disturbance index =6 +/- 1) to 1) evaluates by means of questionnaires the short term (2 month) efficacy of the application of radiofrequency energy at the level of the soft palate, and 2) assess the morbidity associated with this treatment in this population. In the group of patients receiving treatment at three sites in a maximum of three sessions, the short term satisfaction rate was 75 %. The postoperative pain was of minor importance and the use of major analgesics was necessary in 2 cases only. We conclude that this treatment with radiofrequency energy seems to be an effective treatment for primary snoring at short term. The morbidity, specially the pain seems to be distinctly inferior compared to UPPP or laser treatment. Further prospective studies on a larger number of patients and with a longer follow-up are absolutely necessary to confirm these results.

Among 30 children with cholesteatoma undergoing surgery at the Bicetre Hospital between 1985 and 1990, 8 had intact tympanic membranes. Since this represents a larger portion of the patient population than would be expected from previously published data, we under-look a critical analysis of the clinical findings. Among these 8 cases, 2 corresponded to the criteria of congenital cholesteatoma with no history of otitis or trauma and 3 corresponded to acquired types with histories of ventilatory intubation, myringoplasty and accidental trauma. Finally, 3 cases were possibly of mixed origin with lesions typical of congenital epithelial rests and a history of commonplace era infections. Based on these observations, the authors review the clinical characteristics and pathogenesis of congenital cholesteatoma and evoke the etiologic impact of trauma, particularly iatrogenic events such as myringoplasty and ventilatory intubation.

The authors report a case of acute mastoiditis in a four year-old boy due to fusobacterium necrophorum. The importance of the complications (septiciemia, lateral sinus thrombosis, meningitis, osteitis) and the fusobacterium necrophorum are the two majors interests of this observation. A review of the literature is performed.

An open operative technique was used in 36 (38%) of 95 patients with chronic cholesteatomatous otitis followed up by the same surgeon between 1986 and 1990. Although a good anatomical result was obtained in 88% of cases the functional result was less evident, since 57% of patients were left with a liminal tonal loss of less than 30 décibels. The reasons for using an open technique are analyzed, but in only 5% of cases could the possibility of using a closed technique be envisaged, making the classical discussion between open and closed methods of treatments of only academic interest. Petromastoidian evidement with reorganization of the cavity is considered to be effective therapy for cholesteatoma, but indications and technical procedures must be adhered to strictly.

The syndrome combining velar myoclonia with objective tinnitus is rare and, in adults, it corresponds most of the times to a neurological lesion of the dento-olivary tractus. Its functional manifestations are often invalidating and propounded medical treatments uneffective. The authors report a case in which local injection of botulinus toxin allowed to obtain satisfactory functional improvement. Such therapy may prove useful when conventional management is failing.

Limited resection in partial surgery for carcinoma of the larynx leads to discussion of three surgical attitudes: total surgical resection as a matter of principle, additional treatment by radiotherapy, or waiting, with the need for strict surveillance. The present study reports the results of this latter attitude adopted in 23 cases out of 24 of limited resection in a group involving 119 partial laryngectomies (vertical or horizontal) consisting of: 57 cordectomies, 20 hemilaryngectomies, 42 supraglottal laryngectomies. Results of analysis show that there was no recurrence and patients were well with a 3 year follow-up in 19 cases of limited resection out of 24. Overall survival following limited resection was identical to that seen after satisfactory resection, but there was a marked difference with insufficient resection (X2 significant) Following partial laryngeal surgery involving a limit resection, it is felt to be legitimate to temporise as long as the patient can be seen regularly. Such an approach would not seem to modify the overall survival in these patients.

Congenital laryngeal anomalies are a frequent cause of obstructive dyspnea in neonates and young infants, and raise diagnostic and emergency treatment problems. Clinical symptomatology includes stridor of variable severity, obstructive dyspnea and deglutition disorders, but a less typical picture may be seen of apnea, cyanotic episodes, bradycardia and even cardiac arrests. A retrospective study of 687 case-reports of infants treated between 1974 and 1983 was conducted. Lesions included essential congenital laryngeal stridor (laryngomalacia) in 378 cases (50%), of which 15% were severe with respiratory distress and/or deglutition disorders; laryngeal palsy in 161 cases (23%), bilateral in 56 and unilateral in 105 cases; laryngeal incoordination in 23 cases; laryngeal stenosis: 79 cases (11%) including 58 subglottic and 18 dysphragmatic stenoses and 3 atresias; subglottic hematoma: 49 cases; ary-epiglottic or glosso-epiglottic cyst: 15 cases; laryngeal diastema: 11 cases; and bifid epiglottis: 1 case. Clinical, radiologic and endoscopic findings, and the principal therapies used, are discussed for each anomaly.