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Background: Fibromyalgia (FM) is a chronic condition related to dysfunctional central pain processing mechanisms, which affects 3-6% of the world population, leading to widespread pain, stiffness, and tenderness of the muscles, tendons, and joints, as well as restless sleep, fatigue, depression, and anxiety. Exercise is the most effective way of reducing pain and improving global well-being in people with FM, but such patients present an important limitation to exercise adherence. Objective: We aim to evaluate whether a home-based gamification strategy will improve the Fibromyalgia Impact Questionnaire Revised (FIQR) scores in female patients aged 18-60 years old as an alternative to traditional exercise. Methods: The proposed trial is a multicenter, phase II, open-label, parallel, randomized, superiority trial. Female patients ranging from 18 to 60 years old with a diagnosis of FM will be randomized to the intervention group, designed to play the Nintendo Switch Ring Fit Adventure game on three home-based weekly sessions, or to the control group, which will receive general educational guidance through videos and pamphlets provided by the study staff for a total of 12 weeks. The primary outcome will be the mean change in FIQR score results. Discussion: The development of new strategies to increase exercise adherence can enhance the control of symptoms such as pain, depression, low quality of sleep, and physical limitation in FM patients, thereby improving their quality of life. We believe that gamification strategies such as the one used here can make physical activity more playful, accessible, and dynamic, motivating patients and increasing their physical function compared to those seeking center-based or conventional exercises.

BACKGROUND Cystatins are epithelial protease inhibitors that participate in sinonasal immunity and inflammation. Nasal mucus-derived exosomes (NMDEs) are small vesicles secreted by epithelial cells that carry protein cargo reflective of their host cell. NMDEs have been used as a noninvasive biomarker source to study chronic rhinosinusitis with nasal polyps (CRSwNP) proteomics with superior sensitivity to whole mucus. The purpose of this study was to noninvasively quantify exosomal cystatins in a heterogenous population to determine their utility in predicting phenotype and disease severity. METHODS This was an Institutional Review Board-approved study in which NMDEs were purified from 105 patients undergoing sinonasal surgery by ultracentrifugation. Demographic and clinical variables were collected and phenotypes were assigned a priori. Linear discriminant analysis was executed based on normalized Cystatin values as phenotype predictor variables. Unsupervised cluster analysis was performed using Ward's linkage followed by Duda/Hart Je(2)/Je(1) index cluster stopping rules. Analysis of variance (ANOVA), Welch's test, and Fisher's exact tests were used for continuous and categorical variables. RESULTS NMDE Cystatin-2 expression segregated by phenotype (mean ± standard error [SEM]): control (23.4 ± 4.2 pg/µg, n = 32); CRS without NP (CRSsNP) (56.6 ± 8.3 pg/µg, n = 33); and CRSwNP (130.5 ± 16.7 pg/µg, n = 40) (p < 0.0001). Seven clusters were identified among patients where the highest NMDE Cystatin-2 levels clustered with asthma, tissue eosinophilia, and aspirin-exacerbated respiratory disease (AERD). CONCLUSION Cystatin levels in NMDEs predict CRS phenotype and disease severity. As a "liquid biopsy," noninvasive NMDE collection offers a promising opportunity to study disease pathophysiology, discriminate disease states, and potentially reveal novel therapeutic targets.

Chronic rhinosinusitis (CRS) is a heterogeneous definition that includes different disease states that usually are associated with abnormal inflammatory responses. Besides being prevalent, the mechanisms involved in its pathogenesis are not clear and there are few therapeutic options with tolerable side effects. P-glycoprotein (P-gp) is an efflux pump responsible of extruding xenobiotics and cellular metabolites from multiple cell types. It has been widely studied in the cancer field, due to its ability to confer resistance to chemotherapy. It also promotes Type 2 helper T-cell polarizing cytokine secretion in CRS and may represent a potential target to differentiate subtypes of CRS and personalize treatment. This state-of-the-art review explores current knowledge on the participation of P-gp in the pathogenesis of CRS, the P-gp inhibition as a novel targeted therapeutic strategy and the exosomal P-gp test, a non-invasive biomarker that can represent an important advance in the field of rhinology. Keywords: Sinusitis, ATP binding cassette transporter, sub-family B, Verapamil, Exosomes, Nasal polyps, Nasal mucosa

BACKGROUND Oral steroids, traditionally thought of as immunosuppressive agents that are broad in their immunomodulatory effects, are a mainstay of treatment to reduce disease burden in chronic rhinosinusitis with nasal polyps (CRSwNP). The purpose of this study was to determine how differentially expressed proteins in CRSwNP are affected by oral steroid therapy. METHODS Matched exosomal proteomic arrays were quantified using aptamer-based methods in systemic steroid-naive CRSwNP patients before and after a standardized oral prednisone course (n = 12). Previously identified differentially expressed proteins in CRSwNP patients were compared to determine the effect of steroids on expression. Fisher's exact test and t test were applied to normalized protein expression profiles to determine significance. RESULTS Of 18 proteins previously identified to be highly underexpressed in CRSwNP, 16 (89%) had an average increase after systemic steroid treatment (p < 0.05). Lactoperoxidase, initially present at 9-fold lower concentrations in CRSwNP subjects, increased by 209% after steroid treatment. A similar trend was observed with other proteins of interest, including platelet factor 4 and C-C motif ligand 28. The converse of this steroid effect was not true; of the 53 proteins that are highly overexpressed in CRSwNP, only 22 (42%) decreased in quantity with steroid use. CONCLUSION Proteomic analysis of differentially expressed proteins in CRSwNP demonstrates that systemic steroids cause almost uniform upregulation of transcriptionally decreased proteins, whereas the effects of steroids on transcriptionally increased proteins are more heterogeneous. Thus, proteomic analysis may be an effective tool to understand specific therapeutic benefits of steroid use in polyp disease and to create more targeted treatments.

Objective To analyze the incidence of otorrhea in the postoperative period of patients submitted to tympanotomy to place ventilation tube, and who did not protect the ear when exposed to water. Methods Open, randomized-controlled trial. Eighty patients submitted to unilateral or bilateral ear grommet tympanostomy were included and divided into two groups: Auricular Protection and Non-Protection to water during bathing and activities in water. Results In the first postoperative month, the Non-Protection Group presented a significant increase in the number of patients with otorrhea and in the incidence. Four patients of the Protection Group (11%) presented at least one episode of otorrhea in this period, representing an incidence of 0.11 (standard deviation ±0.32) episode/month, whereas in the Non-Protection Group there were 12 episodes (33%; p=0.045) and incidence of 0.33 (±0.48; p=0.02). Between the 2nd and the 13th postoperative months, there was no difference between groups. Seven patients in the Protection Group (20%) had at least one episode of otorrhea, representing an incidence of 0.04 (±0.09) episodes/month, while in the Non-Protection Group there were seven episodes (22%; p=0.8) and incidence of 0.05 (±0.1; p=0.8). Conclusion Patients who underwent ear protection when exposed to water had a lower incidence of otorrhea in the first postoperative month than those who did not undergo protection. From the second month, there was no difference between groups. RESUMO Objetivo Avaliar a incidência de otorreia no período pós-operatório em pacientes submetidos à timpanotomia para colocação de tubo de ventilação e que não realizaram proteção auricular quando expostos à água. Métodos Ensaio clínico controlado, aberto e randomizado. Foram incluídos 80 pacientes submetidos à timpanotomia para colocação de tubo de ventilação unilateral ou bilateral, divididos em dois grupos: Grupo Proteção e Grupo Não Proteção auricular da água durante o banho e as atividades aquáticas. Resultados No primeiro mês pós-operatório, o Grupo Não Proteção apresentou aumento significativo tanto no número de pacientes com otorreia quanto na incidência. Quatro pacientes do Grupo Proteção (11%) apresentaram ao menos um episódio de otorreia neste período, representando incidência de 0,11 (desvio padrão ±0,32) episódio/mês, enquanto no Grupo Não Proteção ocorreram 12 episódios (33%; p=0,045) e incidência de 0,33 (±0,48; p=0,02). Entre o 2º e o 13º meses pós-operatórios, não houve diferença entre os grupos. Sete pacientes do Grupo Proteção (20%) apresentaram ao menos um episódio de otorreia, representando incidência de 0,04 (±0,09) episódios/mês, enquanto no Grupo Não Proteção foram registrados sete episódios (22%; p=0,8) e incidência de 0,05 (±0,1; p=0,8). Conclusão Pacientes que realizaram a proteção auricular quando expostos à água apresentaram menor incidência de otorreia no primeiro mês pós-operatório do que aqueles que não a realizaram. A partir do segundo mês, não houve diferença entre os grupos.

Background: Cancer is the second leading cause of death globally. Up to 86% of advanced cancer patients experience significant pain, while 10-20% live in chronic pain. Besides, increasing prescription of opioids resulted in 33,000 deaths in the US in 2015. Both reduce patients’ functional status and quality of life. While cancer survival rates are increasing, therapeutic options for chronic opioid refractory pain are still limited. Esketamine is the s-enantiomer of ketamine, with superior analgesic effect and less psychotomimetic side effects. Intranasal esketamine was approved by the FDA for treatment-resistant depression. However, its use in chronic cancer pain has never been tested. Therefore, we propose a phase II, randomized, placebo-controlled trial to evaluate the efficacy and safety of intranasal esketamine in chronic opioid refractory cancer pain. Methods and analysis: We will recruit 120 subjects with chronic opioid refractory pain, defined as pain lasting more than 3 months despite optimal therapy with high dose opioids (>60 mg morphine equivalent dose/day) and optimal adjuvant therapy. Subjects will be randomized into two groups: intranasal esketamine (56mg) and placebo. Treatment will be administered twice a week for four consecutive weeks. The primary outcome is defined as reduction in the Numeric Pain Rating Scale (NPRS) after first application. Secondary outcomes include NPRS reduction after four weeks, the number of daily morphine rescue doses, functional status and satisfaction, and depression. Conclusion: This study may extend therapeutic options in patients with chronic pain, thus improving their quality of life and reducing opioid use. Trial registration: Clinical Trials.gov, NCT04666623. Registered on 14 December 2020

INTRODUCTION: Extranodal NK/T-Cell lymphoma, nasal type (NKTLN) is a disease that mainly affects the nasal cavity and the paranasal sinuses. Early nasal symptoms are nonspecific, simulating sinus infection. With disease progression, necrosis of the nasal mucosa increases, hindering histological diagnosis. Thus, multiple biopsies may be necessary until definitive diagnosis. Most studies on NKTLN address the hematological and immunological aspects of the disease. OBJECTIVES: To present data from a Brazilian quaternary hospital, with emphasis on the clinical aspects of the disease, and to correlate the findings with the most recent literature data. METHODS: Case study of seven patient files. RESULTS: Patients were evaluated on their medical history, number of biopsies necessary, association with Epstein-Barr virus, treatment, and outcome. All patients had nonspecific nasal complaints and underwent at least three cycles of antibiotic therapy. The earlier a biopsy was performed, the fewer biopsies were required to diagnose the disease and start treatment. However, this fact did not translate into better prognosis. CONCLUSION: The otolaryngologist plays a fundamental role in the prognosis of NKTLN and can shorten time between symptom onset and treatment of the patient. INTRODUÇÃO: O linfoma extranodal de células NK/T tipo nasal (LNKTN) é uma doença que acomete preferencialmente a cavidade nasal e os seios paranasais. Os sintomas nasais iniciais são inespecíficos, mimetizando um quadro de infecção nasossinusal. Com a progressão da doença, aumenta a necrose da mucosa nasossinusal, dificultando o diagnóstico histológico e podendo ser necessárias múltiplas biópsias até o diagnóstico definitivo. A maioria dos estudos sobre o LNKTN aborda aspectos imunológicos e hematológicos da doença. OBJETIVO: Apresentar a casuística de um hospital quaternário brasileiro, destacando os aspectos clínicos dos pacientes e correlacionando aos achados mais recentes da literatura. MÉTODO: Estudo de casos de sete pacientes. RESULTADOS: Pacientes foram avaliados quanto a aspectos de sua história clínica, número de biópsias necessárias, associação ao EBV, tratamento e evolução. Todos iniciaram o quadro com queixas inespecíficas nasais e foram submetidos a pelo menos três ciclos de antibióticos. Quanto mais precocemente a biópsia foi realizada, menos biópsias foram necessárias para se obter o diagnóstico e iniciar o tratamento. Entretanto, esta situação não refletiu num melhor prognóstico dos pacientes. CONCLUSÃO: O otorrinolaringologista tem papel fundamental no prognóstico do LNKTN, podendo encurtar o tempo entre o início dos sintomas e o tratamento do paciente.