Brazilian guideline for the use of immunobiologicals in chronic rhinosinusitis with nasal polyps ‒ 2024 update.

INTRODUCTION: Biologics targeting type 2 inflammation have revolutionized the way we treat patients with Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). Particularly in severe and difficult-to-control cases, these drugs have provided a new reality for these patients, allowing for the effective and safe treatment of extensive diseases that were not completely managed with the typical strategy of surgery and topical medications. OBJECTIVES: The experience achieved with the approval of these medications by ANVISA for use in CRSwNP and the knowledge obtained regarding outcomes, adverse effects, and the ideal patient profile prompted the update of the previously published guideline, with a detailed review of the most recent scientific literature, the personal experiences of experts, and the adaptation to the reality of the Brazilian healthcare system, both public and private. RESULTS: We proposed a new eligibility criterion for biologics in patients with CRSwNP based on four pillars of indication: the impact of the disease on the patient's life, whether in the presence of specific symptoms or in overall quality of life; the extent of sinonasal disease; the presence of type 2 comorbidities, considering other associated diseases that may also benefit from anti-T2 biologics, and the presence of biomarkers to define type 2 inflammation, especially those associated with worse disease prognoses. CONCLUSIONS: This innovative and pioneering method has two major advantages. First, it ensures a comprehensive evaluation of patients; second, it is flexible, as advancements in our understanding of the disease and changes in cost-effectiveness can be addressed by simply adjusting the required score for indication, without the need to modify the entire evaluation scheme.

Guideline for the use of immunobiologicals in chronic rhinosinusitis with nasal polyps (CRSwNP) in Brazil / Diretriz para o uso dos imunobiológicos em rinossinusite crônica com pólipo nasal (RSCcPN) no Brasil

Abstract Introduction Severe uncontrolled chronic rhinosinusitis with nasal polyps has a negative impact on an individual's quality of life. Therefore, new biologics have emerged for use in specific phenotypes of chronic rhinosinusitis, changing the paradigms of its treatment. Objective To review the current status of biologic treatment indications in chronic rhinosinusitis. Methods The Brazilian Academy of Rhinology brought together different specialists to suggest a course of action, considering its particularities and aspects related to the national reality. Results Of particular interest for decision making will be the identification of subgroups of patients refractory to pre-existing treatment options and the construction of a strategy that improves their quality of life, with the best cost-benefit ratio. Conclusion The use of biologics is a valid option for treatment in more severe cases. This strategy must be better understood and improved in the future, with more studies and greater clinical experience.

Resumo Introdução A rinossinusite crônica com pólipos nasais grave não controlada impacta negativamente na qualidade de vida do indivíduo. Para esses casos, novos imunobiológicos têm surgido, para uso em fenótipos específicos da rinossinusite crônica, e mudaram os paradigmas de seu tratamento. Objetivo Revisar o estado atual das indicações de imunobiológicos em rinossinusite crônica. Método A Academia Brasileira de Rinologia reuniu diferentes especialistas para sugerir uma conduta que considerasse suas particularidades e seus aspectos relacionados à realidade nacional. Resultados De particular interesse para a tomada de decisão serão a identificação dos subgrupos de pacientes refratários às opções de tratamento pré-existentes e a construção de uma estratégia que realmente melhore a qualidade de vida deles, dentro da melhor relação custo-benefício. Conclusão O uso de imunobiológicos é uma opção válida para tratamento em casos mais graves. Essa estratégia deve ser mais bem compreendida e aprimorada no futuro, com mais estudos e maior experiência clínica.

Guideline for the use of immunobiologicals in chronic rhinosinusitis with nasal polyps (CRSwNP) in Brazil.

INTRODUCTION: Severe uncontrolled chronic rhinosinusitis with nasal polyps has a negative impact on an individual's quality of life. Therefore, new biologics have emerged for use in specific phenotypes of chronic rhinosinusitis, changing the paradigms of its treatment. OBJECTIVE: To review the current status of biologic treatment indications in chronic rhinosinusitis. METHODS: The Brazilian Academy of Rhinology brought together different specialists to suggest a course of action, considering its particularities and aspects related to the national reality. RESULTS: Of particular interest for decision making will be the identification of subgroups of patients refractory to pre-existing treatment options and the construction of a strategy that improves their quality of life, with the best cost-benefit ratio. CONCLUSION: The use of biologics is a valid option for treatment in more severe cases. This strategy must be better understood and improved in the future, with more studies and greater clinical experience.

Evaluation of the frequency of non-motor symptoms of Parkinson's disease in adult patients with Gaucher disease type 1.

BACKGROUND: Gaucher disease (GD) is caused by deficiency of beta-glucocerebrosidase (GCase) due to biallelic variations in the GBA1 gene. Parkinson's disease (PD) is the second most common neurodegenerative condition. The classic motor symptoms of PD may be preceded by many non-motor symptoms (NMS), which include hyposmia, rapid eye movement (REM) sleep behavior disorder, constipation, cognitive impairment, and depression. Population studies have identified mutations in GBA1 as the main risk factor for idiopathic PD. The present study sought to evaluate the prevalence of NMS in a cohort of patients with GD type 1 from Southern Brazil. METHODOLOGY: This is an observational, cross-sectional study, with a convenience sampling strategy. Cognition was evaluated by the Montreal Cognitive assessment (MoCa), daytime sleepiness by the Epworth Scale, depression by the Beck Inventory, constipation by the Unified Multiple System Atrophy Rating Scale, and REM sleep behavior disorder by the Single-Question Screen; hyposmia by the Sniffin' Sticks. Motor symptoms were assessed with part III of the Unified Parkinson's Disease Rating Scale. All patients were also genotyped for the GBA1 3'-UTR SNP (rs708606). RESULTS: Twenty-three patients (female = 13; on enzyme replacement therapy = 21, substrate reduction therapy = 2) with a mean age of 41.45 ± 15.3 years (range, 22-67) were included. Eight patients were found to be heterozygous for the 3'-UTR SNP (rs708606). Fourteen patients (8 over age 40 years) presented at least one NMS; daytime sleepiness was the most frequent (n = 10). Two patients (aged 63 and 64, respectively) also presented motor symptoms, probably drug-related. CONCLUSIONS: NMS were prevalent in this cohort. We highlight the importance of a multidisciplinary follow-up focusing on earlier diagnosis of PD, especially for patients with GD type 1 over the age of 40.

Anatomical terminology of the internal nose and paranasal sinuses: cross-cultural adaptation to Portuguese / Anatomical terminology of the internal nose and paranasal sinuses: cross-cultural adaptation to Portuguese

Abstract Introduction: Functional endonasal endoscopic surgery is a frequent surgical procedure among otorhinolaryngologists. In 2014, the European Society of Rhinology published the "European Position Paper on the Anatomical Terminology of the Internal Nose and Paranasal Sinuses", aiming to unify the terms in the English language. We do not yet have a unified terminology in the Portuguese language. Objective: Transcultural adaptation of the anatomical terms of the nose and paranasal cavities of the "European Anatomical Terminology of the Internal Nose and Paranasal Sinuses" to Portuguese. Methods: A group of rhinologists from diverse parts of Brazil, all experienced in endoscopic endonasal surgery, was invited to participate in the creation of this position paper on the anatomical terms of the nose and paranasal sinuses in the Portuguese language according to the methodology adapted from that previously described by Rudmik and Smith. Results: The results of this document were generated based on the agreement of the majority of the participants according to the most popular suggestions among the rhinologists. A cross-cultural adaptation of the sinonasal anatomical terminology was consolidated. We suggest the terms "inferior turbinate", "nasal septum", "(bone/cartilaginous) part of the nasal septum", "(middle/inferior) nasal meatus", "frontal sinus drainage pathway", "frontal recess" and "uncinate process" be standardized. Conclusion: We have consolidated a Portuguese version of the European Anatomical Terminology of the Internal Nose and Paranasal Sinuses, which will help in the publication of technical announcements, scientific publications and the teaching of the internal anatomical terms of the nose and paranasal sinuses in Brazil.

Resumo: Introdução: A cirurgia endoscópica funcional endonasal é um procedimento cirúrgico frequente entre os otorrinolaringologistas. Em 2014, a Sociedade Europeia de Rinologia publicou o "Documento Europeu para Posicionamento sobre a Terminologia Anatômica Interna do Nariz e das Cavidades Paranasais" com o objetivo de unificar os termos na língua inglesa. Ainda não dispomos de uma terminologia unificada na língua portuguesa. Objetivo: Adaptação transcultural dos termos anatômicos do nariz e das cavidades paranasais para o português da "European Anatomical Terminology of the Internal Nose and Paranasal Sinuses". Método: Um grupo de rinologistas de todo o Brasil, com experiência em cirurgia endoscópica endonasal, foi convidado a participar da elaboração desse posicionamento sobre os termos anatômicos do nariz e das cavidades paranasais para o português conforme metodologia adaptada da previamente descrita por Rudmik e Smith. Resultados: Os resultados desse documento foram gerados a partir da concordância da maioria dos participantes conforme as sugestões mais populares entre os rinologistas. Uma adaptação transcultural da terminologia anatômica nasossinusal foi consolidada. Sugerimos que se busque uniformizar termos como "concha inferior", "septo nasal", "porção (óssea/cartilaginosa) do septo nasal", "meato (médio/ inferior) nasal", "via da drenagem do seio frontal", "recesso frontal" e "processo uncinado". Conclusão: Consolidamos uma versão adaptada em português da "European Anatomical Terminology of the Internal Nose and Paranasal Sinuses" que auxiliará a publicação de comunicados técnicos, publicações científicas e o ensino dos termos anatômicos internos do nariz e das cavidades paranasais no Brasil.

Anatomical terminology of the internal nose and paranasal sinuses: cross-cultural adaptation to Portuguese.

INTRODUCTION: Functional endonasal endoscopic surgery is a frequent surgical procedure among otorhinolaryngologists. In 2014, the European Society of Rhinology published the "European Position Paper on the Anatomical Terminology of the Internal Nose and Paranasal Sinuses", aiming to unify the terms in the English language. We do not yet have a unified terminology in the Portuguese language. OBJECTIVE: Transcultural adaptation of the anatomical terms of the nose and paranasal cavities of the "European Anatomical Terminology of the Internal Nose and Paranasal Sinuses" to Portuguese. METHODS: A group of rhinologists from diverse parts of Brazil, all experienced in endoscopic endonasal surgery, was invited to participate in the creation of this position paper on the anatomical terms of the nose and paranasal sinuses in the Portuguese language according to the methodology adapted from that previously described by Rudmik and Smith. RESULTS: The results of this document were generated based on the agreement of the majority of the participants according to the most popular suggestions among the rhinologists. A cross-cultural adaptation of the sinonasal anatomical terminology was consolidated. We suggest the terms "inferior turbinate", "nasal septum", "(bone/cartilaginous) part of the nasal septum", "(middle/inferior) nasal meatus", "frontal sinus drainage pathway", "frontal recess" and "uncinate process" be standardized. CONCLUSION: We have consolidated a Portuguese version of the European Anatomical Terminology of the Internal Nose and Paranasal Sinuses, which will help in the publication of technical announcements, scientific publications and the teaching of the internal anatomical terms of the nose and paranasal sinuses in Brazil.

Rhinosinusitis in autologous and allogeneic bone marrow transplantation: a retrospective study on the performance of imaging studies on severity and prognostic evaluation / Rinossinusite em transplante de células-tronco hematopoéticas autólogo e alogênico: um estudo retrospectivo sobre o desempenho de estudos de imagem na avaliação de severidade e prognóstico

The objective of this work was to evaluate the diagnostic and prognostic performance of a traditional imaging staging system for rhinosinusitis in the bone marrow transplantation (BMT) scenario. A retrospective cohort study was carried out at a bone marrow transplantation referral center involving subjects who underwent allogeneic or autologous BMT from September 1st 2005 to September 31st 2007 and later evolved with rhinosinusitis during the BMT inpatient period. Patients who had a previous history of sinusal disease or otolaryngologic surgery were excluded from the study. Data concerning mortality, the treatment of rhinosinusitis and BMT outcomes were extracted from medical files. The collected parameters were compared to the Lund-Mackay tomographic staging system score which was calculated based on available tomography films of each patient. A total of 85 BMT were performed and 23 allogeneic and 14 autologous (43.5 percent) BMT patients evolved with rhinosinusitis during transplantation. A significant association with LMS was found for the absolute neutrophil count (ANC), with a higher ANC (>500/mm3) correlating with a higher LMS (Mean LMS for lower ANC 6.08 and higher ANC 9.71 points, p<0.05). Need for surgical management and post-BMT admissions, the resolution of the rhinosinusitis and overall mortality had no significant correlation with LMS. Patients with less than 500 neutrophils/mm3 are known to be prone to more severe infections, but paradoxically showed lower LMS when developing rhinosinusitis. However, there were no differences in the main outcomes between those with higher and lower LMS. This would possibly lead to an equivocal assumption of a less severe disease. Severely neutropenic patients are probably not able to mount an effective inflammatory response capable of inducing significant tomographic abnormalities. So, this imaging study would not be able to adequately evaluate the extent of sinusal involvement. We thus ...

O objetivo deste trabalho foi avaliar o desempenho diagnóstico e prognóstico de um escore de estadiamento de rinossinusite (RS) por tomografia em pacientes submetidos a transplante de medula óssea (TMO). Realizou-se um estudo de coorte retrospectivo de pacientes submetidos a transplante de medula óssea (autólogo e alogênico) de 1º de setembro de 2005 a 31 de setembro de 2007 que desenvolveram RS durante o período de internação do transplante. Pacientes com história prévia de doença sinusal ou cirurgia otorrinolaringológica foram excluídos do estudo. Dados relacionados à mortalidade, resolução da RS e desfechos do TMO foram extraídos do prontuário médico. Os parâmetros coletados foram correlacionados com o escore de estadiamento de Lund-Mackay (ELM), que foi calculado com base nas alterações tomográficas de cada paciente. Um total de 85 TMO foram realizados e 37 (23 alogênicos e 14 autólogos) destes pacientes desenvolveram RS durante o transplante. Uma correlação significativa com o ELM foi encontrada quando se considerava a contagem absoluta de neutrófilos (CAN), com uma CAN mais alta (>500/mcl) se associando com um ELM de maior valor (média de escore para CAN baixa 6,08 e CAN alta 9,71 pontos, p<0,05). A necessidade de intervenção cirúrgica e reinternações pós-TMO, resolução da RS e mortalidade geral não mostraram correlação com o ELM. Mesmo assumindo que a neutropenia severa é um fator de risco relevante para intercorrências infecciosas durante o TMO, paradoxalmente, os pacientes com menos de 500 neutrófilos/mcl mostraram um ELM de menor severidade, embora não tenham evoluído de maneira diferente daqueles com maior ELM. É provável que ELM mais alto esteja simplesmente ligado ao fato de uma CAN mais alta levar a uma maior reação inflamatória e consequente alteração tomográfica. Desta forma, o ELM não parece útil na avaliação de pacientes altamente imunossuprimidos como os do TMO. Rev. Bras. Hematol. Hemoter.

Efficacy and safety of Sultamicillin (Ampicillin/Sulbactan) and Amoxicillin/Clavulanic acid in the treatment of upper respiratory tract infections in adults--an open-label, multicentric, randomized trial.

UNLABELLED: Upper respiratory tract infections are the most common causes of medical visits in children and adults, demanding massive use of antibiotics. Bacterial resistance caused by beta-lactamase is one of the most serious problems in this matter. Sultamicillin, a double pro-drug of Ampicillin/Sulbactan, is a potent beta-lactamase inhibitor which can face this challenge. AIM: Evaluate efficacy, safety and tolerability of Ampicillin/Sulbactan compared to Amoxicillin/Clavulanate in upper respiratory tract infections in adults. METHODS: 102 patients were enrolled and randomized to receive Ampicillin/Sulbactan or Amoxicillin/Clavulanate during 10 days. They were evaluated 10 and 30 days after treatment to learn about the therapeutic response. RESULTS: There were no differences between the two groups respecting cure at the end of treatment (visit 2) or at the end of the study (visit 3). Cure ratio was 61.7% and 93.2% (visits 2 and 3) in the Amoxicillin/Clavulanate group compared to 64.4% and 97.4%, respectively, in Ampicillin/Sulbactan group. The adverse events ratio for the two groups was the same (p=0.940). The number of patients with diarrhea was greater in the group of patients receiving Amoxicillin/Clavulanate (70.6%) than in the group receiving Ampicillin/Sulbactan (29.4%) (p=0.0164). CONCLUSIONS: Ampicillin/Sulbactan is as safe and efficient as Amoxicillin/Clavulanate in the empiric treatment of upper respiratory infections in adults. The low occurrence of diarrhea in the group receiving Ampicillin/Sulbactan needs confirmation in other studies.

Eficácia e segurança de Sultamicilina (Ampicilina/Sulbactam) e Amoxacilina/Clavulanato no tratamento das infecções de via aéreas superiores em adultos: um estudo multicêntrico, aberto e randomizado / Efficacy and safety of Sultamicillin (Ampicillin/Sulbactan) and Amoxicillin/Clavulanic Acid in the treatment of upper respiratory tract infections in adults: an open-label, multicentric, randomized trial

As IVAS em crianças e adultos são os motivos mais freqüentes de consulta médica e os que mais demandam o uso de antibióticos. A crescente resistência bacteriana causada pela produção das beta-lactamases constitui um dos mais sérios problemas atuais. A Sultamicilina é uma pró-droga dupla da ampicilina e do sulbactam, um potente inibidor de beta-lactamases que pode fazer frente a estas dificuldades. OBJETIVO: avaliar a eficácia, segurança e tolerabilidade da Ampicilina/Sulbactan comparada à Amoxacilina/Acido Clavulânico no tratamento de IVAS, em adultos. METODOLOGIA: 102 pacientes com diagnóstico de IVAS foram randomizados em dois grupos recebendo Ampicilina/Sulbactan ou Amoxacilina/Clavulanato por 10 dias. Foram avaliados 10 e 30 dias após para análise da resposta terapêutica. RESULTADOS: Não houve diferença entre os grupos com relação à proporção de pacientes curados ao final do tratamento (visita 2) ou do estudo (visita 3). No grupo que recebeu Amoxacilina/Clavulanato, as proporções de cura foram de 61.7 por cento e 93.2 por cento nas visitas 2 e 3, comparadas a 64.4 por cento e 97.4 por cento, respectivamente, no grupo que recebeu Ampicilina/Sulbactan. A proporção de pacientes que experimentou pelo menos um evento adverso foi semelhante nos dois grupos (p = 0.940). A diarréia foi significativamente mais freqüente no grupo Amoxacilina-Clavulanato (70.6 por cento) do que no grupo Ampicilina/Sulbactan (29.4 por cento), (p=0.0164). CONCLUSÕES: A Ampicilina/Sulbactan é tão segura e eficaz quanto a Amoxacilina/Clavulanato no tratamento empírico de IVAS em adultos. A ocorrência significativamente menor de quadros de diarréia no grupo recebendo Ampicilina/Sulbactan necessita confirmação em estudos posteriores.

Upper respiratory tract infections are the most common causes of medical visits in children and adults, demanding massive use of antibiotics. Bacterial resistance caused by beta-lactamase is one of the most serious problems in this matter. Sultamicillin, a double pro-drug of Ampicillin/Sulbactan, is a potent beta-lactamase inhibitor which can face this challenge. AIM: evaluate efficacy, safety and tolerability of Ampicillin/Sulbactan compared to Amoxicillin/Clavulanate in upper respiratory tract infections in adults. METHODS: 102 patients were enrolled and randomized to receive Ampicillin/Sulbactan or Amoxicillin/Clavulanate during 10 days. They were evaluated 10 and 30 days after treatment to learn about the therapeutic response. RESULTS: There were no differences between the two groups respecting cure at the end of treatment (visit 2) or at the end of the study (visit 3). Cure ratio was 61.7 percent and 93.2 percent (visits 2 and 3) in the Amoxicillin/Clavulanate group compared to 64.4 percent and 97.4 percent, respectively, in Ampicillin/Sulbactan group. The adverse events ratio for the two groups was the same (p=0.940). The number of patients with diarrhea was greater in the group of patients receiving Amoxicillin/Clavulanate (70.6 percent) than in the group receiving Ampicillin/Sulbactan (29.4 percent) (p=0.0164). CONCLUSIONS: Ampicillin/Sulbactan is as safe and efficient as Amoxicillin/Clavulanate in the empiric treatment of upper respiratory infections in adults. The low occurrence of diarrhea in the group receiving Ampicillin/Sulbactan needs confirmation in other studies.

Cytokine profiles in a rat model of otitis media with effusion caused by eustachian tube obstruction with and without Streptococcus pneumoniae infection.

OBJECTIVE: Cytokine expression was studied in a rat model of otitis media with effusion. METHODS: The left eustachian tube was obstructed (eustachian tube obstruction [ETO]) in 84 rats. Forty-two ears were challenged with, and those rats were treated from day 2 to day 7 with ampicillin. Twelve rats (6 per group) were killed on days 1, 2, 7, 21, 35, 56, and 112; mucosa was harvested and assayed for interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-10 (IL-10), interferon-gamma (IFN-gamma), transforming growth factor-beta (TGF-beta), monocyte chemoattractant protein-1 (MCP-1), and interleukin-8 (IL-8) gene expression, and effusion was assayed for IL-1beta, TNF-alpha, IL-6, IL-10, and macrophage inflammatory protein-2 (MIP-2) protein. RESULTS: Most cytokines were detectable in the effusion from infected ears with ETO on days 1 and 2 only. MIP-2 exhibited a biphasic response. Only effusion MIP-2 was consistently detected in uninfected ears with ETO. Three patterns of mucosal cytokine messenger RNA (mRNA) upregulation were observed: isolated early (IL-1beta, IL-8), isolated late (TNF-alpha, IFN-gamma), and biphasic (MCP-1, IL-6, TGF-beta) responses. Early cytokine mRNA upregulations were observed only in the infected ears with ETO, whereas late upregulations were observed in both groups. CONCLUSIONS: Early expression of the assayed cytokines occurred only in ears with active infection. For both groups, a late upregulation of cytokine message but not protein was documented. The profile of cytokine expression during otitis media episodes may be useful in defining etiology, disease stage, and prognosis.

A rat model of otitis media with effusion caused by eustachian tube obstruction with and without Streptococcus pneumoniae infection: methods and disease course.

OBJECTIVE: To describe the clinical and histopathologic progression of a rat model of otitis media with effusion caused by eustachian tube obstruction (ETO) with and without Streptococcus pneumoniae infection. METHODS: In 164 rats, the left, bony eustachian tube was approached via a ventral incision and obstructed with dental material. Then 108 rats were infected via an intrabullar injection with S pneumoniae. At 48 hours, the infected rats were treated for 5 days with ampicillin. All ears were evaluated by weekly otomicroscopy. On each of days 1, 2, 7, 21, 35, 56, and 112, four rats were killed for histologic study. All effusions were cultured for bacteria. RESULTS: Fourteen rats died of surgical complications; effusion resolved by 2 weeks in 9 rats. During the first few days, infected ears with ETO had bulging tympanic membranes, followed by tympanic membrane retraction, purulent effusion, and otorrhea (50%) over the next few weeks, whereas uninfected ears with ETO developed retraction and serous effusion during the same time frame. At later times, all ears with ETO presented with retraction and serous or serous-mucoid effusion. S pneumoniae was recovered only from the infected ears with ETO (days 1 and 2), with some colonization by nonpathogenic microorganisms observed equally in both groups of ears. Histology showed a typical acute inflammatory reaction in the challenged ears with ETO through day 14 and then a chronic inflammation for all ears with ETO. CONCLUSION: The experimental methods provoked reproducible pathologic signs similar to those for otitis media with effusion. Given the availability of rat-specific reagents, this model is well suited for studies of cytokine elaboration during disease pathogenesis.