An atlas of cells in the human tonsil.

Palatine tonsils are secondary lymphoid organs (SLOs) representing the first line of immunological defense against inhaled or ingested pathogens. We generated an atlas of the human tonsil composed of >556,000 cells profiled across five different data modalities, including single-cell transcriptome, epigenome, proteome, and immune repertoire sequencing, as well as spatial transcriptomics. This census identified 121 cell types and states, defined developmental trajectories, and enabled an understanding of the functional units of the tonsil. Exemplarily, we stratified myeloid slan-like subtypes, established a BCL6 enhancer as locally active in follicle-associated T and B cells, and identified SIX5 as putative transcriptional regulator of plasma cell maturation. Analyses of a validation cohort confirmed the presence, annotation, and markers of tonsillar cell types and provided evidence of age-related compositional shifts. We demonstrate the value of this resource by annotating cells from B cell-derived mantle cell lymphomas, linking transcriptional heterogeneity to normal B cell differentiation states of the human tonsil.

Significance of clinical-immunological patterns and diagnostic yield of biopsies in microscopic polyangiitis and granulomatosis with polyangiitis.

BACKGROUND: Microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are the two major antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). OBJECTIVES: To characterize a homogenous AAV cohort and to assess the impact of clinicopathological profiles and ANCA serotypes on clinical presentation and prognosis. Clinical differences in GPA patients according to ANCA serotype and the diagnostic yield for vasculitis of biopsies in different territories were also investigated. RESULTS: This retrospective study (2000-2021) included 152 patients with AAV (77 MPA/75 GPA). MPA patients (96.1% myeloperoxidase [MPO]-ANCA and 2.6% proteinase 3 [PR3]-ANCA) presented more often with weight loss, myalgia, renal involvement, interstitial lung disease (ILD), cutaneous purpura, and peripheral nerve involvement. Patients with GPA (44% PR3-ANCA, 33.3% MPO, and 22.7% negative/atypical ANCA) presented more commonly with ear, nose, and throat and eye/orbital manifestations, more relapses, and higher survival than patients with MPA. GPA was the only independent risk factor for relapse. Poor survival predictors were older age at diagnosis and peripheral nerve involvement. ANCA serotypes differentiated clinical features in a lesser degree than clinical phenotypes. A mean of 1.5 biopsies were performed in 93.4% of patients in different territories. Overall, vasculitis was identified in 80.3% (97.3% in MPA and 61.8% in GPA) of patients. CONCLUSIONS: The identification of GPA presentations associated with MPO-ANCA and awareness of risk factors for relapse and mortality are important to guide proper therapeutic strategies in AAV patients. Biopsies of different affected territories should be pursued in difficult-to-diagnose patients based on their significant diagnostic yield.

The impact of margins in laryngeal cancer patients treated with transoral laser microsurgery: a systematic review and meta-analysis.

PURPOSE: In laryngeal squamous cell carcinoma (LSCC) treated with transoral laser microsurgery (TOLMS), the status of margins significantly affected local control. When a positive or close margin is present, there is no ubiquitous consensus regarding further treatments. The rationale of the present systematic review and meta-analysis is to investigate the survival impact of the status of the margins in patients affected by LSCC treated with TOLMS. DATA SOURCES: PubMed, EMBASE, and Cochrane Library. METHODS: We performed a systematic search, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Inclusion criteria were: patients affected by LSCC, staged according to the American Joint Committee on Cancer Staging System and treated by TOLMS without any previous treatment; margins status (close, positive, negative) and the adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) of overall survival, disease-specific survival, and disease-free survival has to be reported. RESULTS: Nine studies were deemed eligible for the qualitative analysis, and 3 for the quantitative analysis to investigate the association between margin status and OS. The cumulative number of patients was 3130. The sample size ranged from 96 to 747 patients. The follow-up period ranged from 0 to 201 months. The meta-analysis results show that positive margins have an aHR of 1.30 yet with CI range (0.56 to 2.97). CONCLUSIONS: Our current meta-analysis results are unable to definitively assess the real impact of resection margins on OS. Few authors provide accurate data regarding position and types of margins. Further prospective or high-quality studies are required.

An automated approach for real-time informative frames classification in laryngeal endoscopy using deep learning.

PURPOSE: Informative image selection in laryngoscopy has the potential for improving automatic data extraction alone, for selective data storage and a faster review process, or in combination with other artificial intelligence (AI) detection or diagnosis models. This paper aims to demonstrate the feasibility of AI in providing automatic informative laryngoscopy frame selection also capable of working in real-time providing visual feedback to guide the otolaryngologist during the examination. METHODS: Several deep learning models were trained and tested on an internal dataset (n = 5147 images) and then tested on an external test set (n = 646 images) composed of both white light and narrow band images. Four videos were used to assess the real-time performance of the best-performing model. RESULTS: ResNet-50, pre-trained with the pretext strategy, reached a precision = 95% vs. 97%, recall = 97% vs, 89%, and the F1-score = 96% vs. 93% on the internal and external test set respectively (p = 0.062). The four testing videos are provided in the supplemental materials. CONCLUSION: The deep learning model demonstrated excellent performance in identifying diagnostically relevant frames within laryngoscopic videos. With its solid accuracy and real-time capabilities, the system is promising for its development in a clinical setting, either autonomously for objective quality control or in conjunction with other algorithms within a comprehensive AI toolset aimed at enhancing tumor detection and diagnosis.

Persistent lymph nodes after curative chemoradiotherapy for head and neck cancer: imaging predictors of response for decision-making.

PURPOSE: To identify response predictors in patients with head and neck squamous cell carcinoma (N + HNSCC) and persistent lymph nodes after curative chemoradiotherapy treatment (CCRT). MATERIALS AND METHODS: Consecutive patients with N + HNSCC treated with CCRT and persistent lymph nodes at first follow-up between 2015 and 2021 were identified and analyzed. Complete response was defined as the absence of lymph node metastatic involvement in patients with salvage lymphadenectomy or the absence of progression after 1 year of successive follow-ups. Tumour type and location, staging, and human papillomavirus (HPV) status were considered for analysis. The number and size of lymph nodes, type, shape, enhancement and margins on diagnostic and follow-up CT were also analyzed. RESULTS: The cohort included 46 patients with 134 pathological lymph nodes. Logistic regression models showed the following variables to be significant: performance of salvage lymphadenectomy (OR 0.094, [CI 95% 0.004-0.61], p = 0.037); the type of lymphadenopathy on diagnostic CE-CT (solid vs. cystic) (N1: OR = 4.11, [CI 95% 1.11-17.93], p = 0.042 and N3: OR 6.42, [CI 95% 1.2-42.56], p = 0.036); the change of shape (round to oval) on the follow-up CE-CT (OR 9.76, [CI 95% 1.79-8.57], p = 0.016) and the time in days between CCRT and the first follow-up CE-CT (OR 1.06, [CI 95% 1.004-1.13], p = 0.048). CONCLUSIONS: In our experience, the presence of solid lymph nodes on pre-treatment CT and the change in shape from round to oval on post-treatment CT are predictors of response to treatment in patients with N + HNSCC persistent lymph nodes after CCRT. Increasing the temporal interval between treatment and follow-up CT should be considered to avoid unnecessary nodal dissections.

Consensus for voice quality assessment in clinical practice: guidelines of the European Laryngological Society and Union of the European Phoniatricians.

INTRODUCTION: To update the European guidelines for the assessment of voice quality (VQ) in clinical practice. METHODS: Nineteen laryngologists-phoniatricians of the European Laryngological Society (ELS) and the Union of the European Phoniatricians (UEP) participated to a modified Delphi process to propose statements about subjective and objective VQ assessments. Two anonymized voting rounds determined a consensus statement to be acceptable when 80% of experts agreed with a rating of at least 3/4. The statements with ≥ 3/4 score by 60-80% of experts were improved and resubmitted to voting until they were validated or rejected. RESULTS: Of the 90 initial statements, 51 were validated after two voting rounds. A multidimensional set of minimal VQ evaluations was proposed and included: baseline VQ anamnesis (e.g., allergy, medical and surgical history, medication, addiction, singing practice, job, and posture), videolaryngostroboscopy (mucosal wave symmetry, amplitude, morphology, and movements), patient-reported VQ assessment (30- or 10-voice handicap index), perception (Grade, Roughness, Breathiness, Asthenia, and Strain), aerodynamics (maximum phonation time), acoustics (Mean F0, Jitter, Shimmer, and noise-to-harmonic ratio), and clinical instruments associated with voice comorbidities (reflux symptom score, reflux sign assessment, eating-assessment tool-10, and dysphagia handicap index). For perception, aerodynamics and acoustics, experts provided guidelines for the methods of measurement. Some additional VQ evaluations are proposed for voice professionals or patients with some laryngeal diseases. CONCLUSION: The ELS-UEP consensus for VQ assessment provides clinical statements for the baseline and pre- to post-treatment evaluations of VQ and to improve collaborative research by adopting common and validated VQ evaluation approach.

Deep brain stimulation as a palliative treatment for myorhythmia: A case of failure.

BACKGROUND AND PURPOSE: Myorhythmia is a hyperkinetic movement disorder that derives from a disruption of the Guillain-Mollaret triangle, due to an identifiable structural lesion. It is often disabling and with disappointing control under medical treatment. METHODS: Herein, a case of myorhythmia secondary to a vascular insult in the brainstem is reported and an unsuccessful attempt to palliate it with functional neurosurgery. RESULTS: A 67-year-old man displayed a repetitive, rhythmic, slow 2-3 Hz movement, 6 months after suffering a pontomesencephalic hypertensive haematoma. The kinetic phenomenon affected the orbicular and low facial muscles, the neck, the thorax and the upper limbs. Furthermore, he exhibited tremor of the soft palate and pendular nystagmus. On T2-weighted magnetic resonance imaging, hypertrophic degeneration of the inferior olivary complex was seen. He was diagnosed with secondary myorhythmia and multiple pharmacological treatments were tested, but failed. Ultimately, deep brain stimulation with bilateral electrodes placed in the thalamic ventralis intermedius nucleus was offered. Unfortunately, no alleviation of the symptoms was achieved other than mild improvement in involuntary eye movements. CONCLUSIONS: This is the first case to report the use of deep brain stimulation for myorhythmia. Better understanding of the pathophysiology of this condition, and localization of the pacemaker, may allow identification of reliable neurosurgical therapeutic targets.

Alpha-synuclein seeds in olfactory mucosa of patients with isolated REM sleep behaviour disorder.

Isolated REM sleep behaviour disorder (RBD) is an early-stage α-synucleinopathy in most, if not all, affected subjects. Detection of pathological α-synuclein in peripheral tissues of patients with isolated RBD may identify those progressing to Parkinson's disease, dementia with Lewy bodies or multiple system atrophy, with the ultimate goal of testing preventive therapies. Real-time quaking-induced conversion (RT-QuIC) provided evidence of α-synuclein seeding activity in CSF and olfactory mucosa of patients with α-synucleinopathies. The aim of this study was to explore RT-QuIC detection of α-synuclein aggregates in olfactory mucosa of a large cohort of subjects with isolated RBD compared to patients with Parkinson's disease and control subjects. This cross-sectional case-control study was performed at the Medical University of Innsbruck, Austria, the Hospital Clinic de Barcelona, Spain, and the University of Verona, Italy. Olfactory mucosa samples obtained by nasal swab in 63 patients with isolated RBD, 41 matched Parkinson's disease patients and 59 matched control subjects were analysed by α-synuclein RT-QuIC in a blinded fashion at the University of Verona, Italy. Median age of patients with isolated RBD was 70 years, 85.7% were male. All participants were tested for smell, autonomic, cognitive and motor functions. Olfactory mucosa was α-synuclein RT-QuIC positive in 44.4% isolated RBD patients, 46.3% Parkinson's disease patients and 10.2% control subjects. While the sensitivity for isolated RBD plus Parkinson's disease versus controls was 45.2%, specificity was high (89.8%). Among isolated RBD patients with positive α-synuclein RT-QuIC, 78.6% had olfactory dysfunction compared to 21.4% with negative α-synuclein RT-QuIC (P < 0.001). The extent of olfactory dysfunction was more severe in isolated RBD patients positive than negative for olfactory mucosa a-synuclein RT-QuIC (P < 0.001). We provide evidence that the α-synuclein RT-QuIC assay enables the molecular detection of neuronal α-synuclein aggregates in olfactory mucosa of patients with isolated RBD and Parkinson's disease. Although the overall sensitivity was moderate in this study, nasal swabbing is attractive as a simple, non-invasive test and might be useful as part of a screening battery to identify subjects in the prodromal stages of α-synucleinopathies. Further studies are needed to enhance sensitivity, and better understand the temporal dynamics of α-synuclein seeding in the olfactory mucosa and spreading to other brain areas during the progression from isolated RBD to overt α-synucleinopathy, as well the impact of timing, disease subgroups and sampling technique on the overall sensitivity.

Accuracy of liquid-based brush cytology and HPV detection for the diagnosis and management of patients with oropharyngeal and oral cancer.

OBJECTIVES: This study aims to evaluate the usefulness of liquid-based brush cytology for malignancy diagnosis and HPV detection in patients with suspected oropharyngeal and oral carcinomas, as well as for the diagnosis of tumoral persistence after treatment. MATERIAL AND METHODS: Seventy-five patients with suspicion of squamous cell carcinoma of the oropharynx or oral cavity were included. Two different study groups were analyzed according to the date of the sample collection: (1) during the first endoscopy exploration and (2) in the first control endoscopy after treatment for squamous cell carcinoma. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for malignancy diagnosis as well as for HPV-DNA detection on brush cytologies were assessed. RESULTS: Before treatment, the brush cytology showed a sensitivity of 88%, specificity of 100%, and accuracy of 88%. After treatment, it showed a sensitivity of 71%, specificity of 77%, and accuracy of 75%. HPV-DNA detection in cytology samples showed a sensitivity of 85%, specificity of 100%, and accuracy of 91% before treatment and an accuracy of 100% after treatment. CONCLUSIONS: Liquid-based brush cytology showed good accuracy for diagnosis of oropharyngeal and oral squamous cell carcinoma before treatment, but its value decreases after treatment. Nevertheless, it is useful for HPV-DNA detection, as well as to monitor the patients after treatment. CLINICAL RELEVANCE: Brush cytology samples are reliable for the detection of HPV-DNA before and after treatment and may be a useful method to incorporate in the HPV testing guidelines.

Circulating microRNAs modulating glycolysis as non-invasive prognostic biomarkers of HNSCC.

BACKGROUND: The identification of prognostic non-invasive biomarkers is a priority for cancer patients' care. Circulating microRNA (miRNAs) have been described in numerous human malignancies as diagnostic, prognostic, and therapeutic cancer biomarkers. The aim of our study was to analyze the expression profile of a set of miRNAs, involved in the modulation of the glycolytic pathway, as prognostic factors in human head and neck squamous cell carcinomas (HNSCC). METHODS: Serum samples of 54 patients with untreated HNSCC were obtained at the time of diagnosis. The prognostic value of circulating miR-26b, miR-124, miR-155 and miR-375 was evaluated towards disease-free survival. RESULTS: We found that there were optimal miRNAs cut-off values for lower risk of recurrence in HNSCC patients. Kaplan-Meier curves showed that higher levels of miR-26b and lower levels of miR-155 were associated with better disease-free survival rates. In the multivariate analysis, patients with serum miR-26b > 0.062 and miR-155 < 0.159 presented more than 2.9 times lower risk of poor outcome. CONCLUSION: Our results suggest that two miRNAs that modulate the glycolytic pathway, miR-26b and miR-155, are independently associated with the risk of recurrence in patients with HNSCC. The overall results in this study supports the evidence that the glucose homeostasis may be a target to improve the outcomes for patients with HNSCC. LEVEL OF EVIDENCE: Individual retrospective cohort study (2b).

Salvage carbon dioxide transoral laser microsurgery for laryngeal cancer after (chemo)radiotherapy: a European Laryngological Society consensus statement.

PURPOSE: To provide expert opinion and consensus on salvage carbon dioxide transoral laser microsurgery (CO2 TOLMS) for recurrent laryngeal squamous cell carcinoma (LSCC) after (chemo)radiotherapy [(C)RT]. METHODS: Expert members of the European Laryngological Society (ELS) Cancer and Dysplasia Committee were selected to create a dedicated panel on salvage CO2 TOLMS for LSCC. A series of statements regarding the critical aspects of decision-making were drafted, circulated, and modified or excluded in accordance with the Delphi process. RESULTS: The expert panel reached full consensus on 19 statements through a total of three sequential evaluation rounds. These statements were focused on different aspects of salvage CO2 TOLMS, with particular attention on preoperative diagnostic work-up, treatment indications, postoperative management, complications, functional outcomes, and follow-up. CONCLUSION: Management of recurrent LSCC after (C)RT is challenging and is based on the need to find a balance between oncologic and functional outcomes. Salvage CO2 TOLMS is a minimally invasive approach that can be applied to selected patients with strict and careful indications. Herein, a series of statements based on an ELS expert consensus aimed at guiding the main aspects of CO2 TOLMS for LSCC in the salvage setting is presented.

Intra and interobserver agreement of narrow band imaging for the detection of head and neck tumors.

BACKGROUND: Narrow band imaging (NBI) in combination with white light endoscopy (WLE) has improved the accuracy for the diagnosis and follow-up of head and neck carcinomas by identifying changes in the vascular patterns of the mucosa. However, NBI evaluation is explorer-dependent and may be influenced by the learning curve. The aim of this study is to assess the intra and interobserver agreement of NBI and WLE at the office, under local anaesthesia, by either experienced or non-experienced observers. METHODS: Eighty-seven images of head and neck lesions were routinely collected under WLE and NBI. A group of three experienced otolaryngologists and three medical students assessed the images after a brief training. No additional patient information was provided. The same protocol was repeated after three weeks. Intra and interobserver agreement were calculated with the kappa index. RESULTS: NBI intraobserver agreement was substantial (κ = 0.62) and better than with WLE alone, which was moderate (κ = 0.57) in both groups. Interobserver agreement was moderate with WLE (κ = 0.58) and substantial with NBI (κ = 0.63). Both groups improved intraobserver and interobserver agreement with the implementation of NBI. CONCLUSIONS: Intra and interobserver agreement with NBI for the evaluation of head and neck lesions are substantial, and improve the results of WLE alone in both, professionals and trainees.

Survey of Spanish general practitioners' attitudes toward management of sore throat: an internet-based questionnaire study.

BACKGROUND: The management of sore throat varies widely in Europe. The objective of this study was to gain insight into clinicians' perceptions on the current management of sore throat in Spain. METHODS: Cross-sectional, internet-based questionnaire study answered from July to September 2013. General practitioners (GPs) affiliated with the two largest scientific societies of primary care were invited to participate in the study. Questions were asked about physician knowledge, the use of current national guidelines for sore throat management, and management in two clinical scenarios, depicting a young adult with sore throat and: 1. cough, coriza with or without fever, and 2. fever without cough and coriza. RESULTS: The questionnaire was completed by 1476 GPs (5%) and 12.7% declared using rapid antigen detection tests. Antibiotics were considered by 18.8% of the GPs in the first scenario and by 32% in the second scenario (p < 0.001). The antibiotics most commonly mentioned by GPs were amoxicillin and amoxicillin + clavulanate (52.7 and 31.2%, respectively) whereas penicillin V was only prescribed in 11.9% of the cases. The drugs most commonly considered in both scenarios were analgesics and anti-inflammatory drugs. Antitussives, decongestants and expectorants were more commonly prescribed in cases of suspected viral infection (p < 0.001). CONCLUSIONS: GPs have misconceptions as to the indications for using rapid antigen detection tests and prescribing drugs in the management of sore throat. These results suggest that guidelines are seldom followed since one in five GPs declared giving antibiotics for patients with a suspected viral infection and the use of second-choice antibiotics seems considerable.

Long-term quality of life after transoral laser microsurgery for laryngeal carcinoma.

BACKGROUND AND OBJECTIVES: Previous studies showed good short-term Quality of life (QOL) after Transoral Laser Microsurgery (TLM) for laryngeal cancer. Here, we aimed to evaluate QOL after TLM in the long-term. METHODS: Prospective longitudinal study. Sixty-two consecutive disease-free patients were evaluated using UW-QOL v4 and SF-12 questionnaires, 1 and 5 years after TLM. Changes over time were assessed according to age, location, and tumor size. Long-term VHI-10 was also evaluated. RESULTS: The mean follow-up time was 5.41 ± 2.02 years. No differences in the global UW-QOL score were observed between 1 and 5 years after TLM (1135.00 vs. 1127.20; P = 0.4). Activity worsened slightly in the long-term (93.03 vs. 87.70; P = 0.02). Forty-two and 58% of the patients reported that their health 1 and 5 years after treatment was much better than prior to diagnosis. Initially, 3.3% considered their health much worse, which was reduced to 1.7% at 5 years. SF-12 scores remained unchanged for both physical and mental aspects (P > 0.05). The VHI-10 was 3.81 ± 5.7 for supraglottic and 7.2 ± 9.6 for glottic tumors. CONCLUSION: Patients treated with TLM present a very good long-term QOL. Only activity deteriorates over time, while voice and swallowing remain satisfactory in the majority of patients. J. Surg. Oncol. 2016;114:789-795. © 2016 2016 Wiley Periodicals, Inc.

[Recommendations for management of acute pharyngitis in adults]. / Recomendaciones para el manejo de la faringoamigdalitis aguda del adulto.

Acute pharyngitis in adults is one of the most common infectious diseases seen in general practitioners' consultations. Viral aetiology is the most common. Among bacterial causes, the main agent is Streptococcus pyogenes or group A ß-haemolytic streptococcus (GABHS), which causes 5%-30% of the episodes. In the diagnostic process, clinical assessment scales can help clinicians to better predict suspected bacterial aetiology by selecting patients who should undergo a rapid antigen detection test. If these techniques are not performed, an overdiagnosis of streptococcal pharyngitis often occurs, resulting in unnecessary prescriptions of antibiotics, most of which are broad spectrum. Consequently, management algorithms that include the use of predictive clinical rules and rapid tests have been set up. The aim of the treatment is speeding up symptom resolution, reducing the contagious time span and preventing local suppurative and non-suppurative complications. Penicillin and amoxicillin are the antibiotics of choice for the treatment of pharyngitis. The association of amoxicillin and clavulanate is not indicated as the initial treatment of acute infection. Neither are macrolides indicated as first-line therapy; they should be reserved for patients allergic to penicillin. The appropriate diagnosis of bacterial pharyngitis and proper use of antibiotics based on the scientific evidence available are crucial. Using management algorithms can be helpful in identifying and screening the cases that do not require antibiotic therapy.

Prognostic factors of quality of life after transoral laser microsurgery for laryngeal cancer.

We aimed to evaluate factors influencing quality of life (QOL) after transoral laser microsurgery (TLM) of laryngeal cancer. Four hundred and one consecutive disease-free patients were evaluated 1 year after treatment using the University of Washington-QOL v4, the SF-12 (short form of SF-36), and a questionnaire about self-rated health status. The importance of age, gender, tumor location, tumor size, tumor stage, neck dissection and adjuvant treatment were evaluated. One year after TLM patients had a good QOL, with only 6 % of patients reporting a worsening in their health status. Radiation therapy (p = 0.000) and neck dissection (p = 0.000) were negative factors for disease-specific QOL, whereas age ≥ 70 (p = 0.01) was a positive independent factor for mental score of SF-12. Speech was negatively influenced by tumor size (p = 0.001) as was swallowing by age (p = 0.001) and postoperative radiation (p = 0.000). Patients treated with TLM present a good QOL 1 year after surgery. Radiation and neck dissection negatively impact QOL. Elderly patients cope better with their disabilities.

[Recommendations for management of acute pharyngitis in adults]. / Recomendaciones para el manejo de la faringoamigdalitis aguda del adulto.

Acute pharyngitis in adults is one of the most common infectious diseases seen in general practitioners' consultations. Viral aetiology is the most common. Among bacterial causes, the main agent is Streptococcus pyogenes or group A ß-haemolytic streptococcus (GABHS), which causes 5%-30% of the episodes. In the diagnostic process, clinical assessment scales can help clinicians to better predict suspected bacterial aetiology by selecting patients who should undergo a rapid antigen detection test. If these techniques are not performed, an overdiagnosis of streptococcal pharyngitis often occurs, resulting in unnecessary prescriptions of antibiotics, most of which are broad spectrum. Consequently, management algorithms that include the use of predictive clinical rules and rapid tests have been set up. The aim of the treatment is speeding up symptom resolution, reducing the contagious time span and preventing local suppurative and non-suppurative complications. Penicillin and amoxicillin are the antibiotics of choice for the treatment of pharyngitis. The association of amoxicillin and clavulanate is not indicated as the initial treatment of acute infection. Neither are macrolides indicated as first-line therapy; they should be reserved for patients allergic to penicillin. The appropriate diagnosis of bacterial pharyngitis and proper use of antibiotics based on the scientific evidence available are crucial. Using management algorithms can be helpful in identifying and screening the cases that do not require antibiotic therapy.

Five-year follow-up of substantia nigra echogenicity in idiopathic REM sleep behavior disorder.

Hyperechogenicity of the substantia nigra visualized by transcranial sonography occurs in most Parkinson's disease (PD) patients. Idiopathic rapid eye movement (REM) sleep behavior disorder (IRBD) subjects eventually develop PD and other synucleinopathies. This study was undertaken to evaluate whether in IRBD, transcranial sonography identifies subjects who convert to PD and other synucleinopathies, and whether substantia nigra echogenic size changes with time. It was a prospective study in which 55 IRBD patients underwent transcranial sonography at baseline and were invited to follow-up after 5 years. Patients were assessed by the same experienced sonographer who was blinded to clinical data and baseline transcranial sonography results, and used the same equipment and adjustments. Twenty-one (38.2%) subjects were diagnosed with a synucleinopathy (PD in 11, dementia with Lewy bodies in nine, and multiple system atrophy in one). Sensitivity of baseline substantia nigra hyperechogenicity for the development of a synucleinopathy was 42.1%, specificity 67.7%, positive predictive value 44.4%, negative predictive value 65.6%, and relative risk 1.29. No differences were detected between the first and second examination in mean size of the substantia nigra (0.20 ± 0.09 cm(2) vs. 0.19 ± 0.07 cm(2) ; P = 0.777) and in percentage of patients with substantia nigra hyperechogenicity (33.3% vs. 42.8%, P = 0.125). Transcranial sonography of the substantia nigra alone is not a useful tool to identify IRBD subjects at risk for the development of PD or a synucleinopathy after 5 years of follow-up. In IRBD, transcranial sonography cannot be used to monitor the degenerative process in the substantia nigra, because echogenicity size remains stable over time.

Upper airway manifestations of anti-IgLON5 disease: Otorhinolaryngological point of view.

INTRODUCTION: Anti-IgLON5 disease is a recently described neurological disorder with multisystemic features. The disease is characterized by the presence of IgLON5 antibodies in serum and cerebrospinal fluid. Our objective is to describe in detail the otorhinolaryngological manifestations of this disease, which are frequent and may include dysphagia, dysarthria, vocal cord paralysis and laryngospasm. METHODS: In this study, we present a series of 9 patients with anti-IgLON5 disease and otolaryngological manifestations. Patients were evaluated between July 2012 and March 2022 by video-polysomnography, fiber-optic laryngoscopy, and functional endoscopic evaluation of swallowing. RESULTS: The median age was 71 years, and 5 (56%) were female. Video-polysomnography showed a NREM/REM parasomnia in 6 patients (67%), obstructive sleep apnea in 8 (88%), stridor during sleep in 7 (78%) and central apneas in 1 (11%). Six out of the 9 patients (67%) presented episodes of acute respiratory failure that required mechanical ventilation, 6 had vocal fold palsy with 4 of them requiring tracheostomy (3 had to be performed on an emergency basis). Dysphagia occurred in 8 patients (89%). Prominent upper airway secretion and sialorrhea was also present in 3 cases. CONCLUSION: The anti-IgLON5 disease exhibits extensive otolaryngological symptoms, mainly affecting the upper airway. These symptoms affect the quality of life and can be life-threatening. Prompt acute management is essential for stridor, dyspnea, and dysphagia. Given the potential severity of the symptoms and rarity of the disease, it is important for otolaryngologists to be familiar with anti-IgLON5 disease. LEVEL OF EVIDENCE: Level 4.