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1.
Eur Arch Otorhinolaryngol ; 281(1): 227-235, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37658224

RESUMO

PURPOSE: To describe the self-reported practices on the diagnosis, treatment, and follow-up of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) by ear, nose, and throat (ENT) specialists in Spain to identify potential areas for management optimization. METHODS: A cross-sectional online survey with 16 questions was carried out. Recruitment was performed by emailing registered ENT specialists in the Spanish Society of Otorhinolaryngology and Head and Neck Surgery (SEORL-CCC). RESULTS: In total, 127 ENT specialists completed the survey. Fifty-one percent of respondents combined clinical criteria and objective evidence of mucosal inflammation to diagnose CRSwNP. Patient interview and, to a lower degree, a visual analogue scale were the most employed diagnostic tools to quantify symptom severity. Less than half (45%) routinely used the 22-item sino-nasal outcomes test (SNOT-22) to assess the impact of CRSwNP disease in quality of life. The use of patient-reported outcomes and other clinical evaluation tools showed a larger uptake among ENT specialists that worked at an ENT department with an available rhinology unit. Almost all the specialists surveyed (95%) recommended biological treatment, particularly in patients with uncontrolled CRSwNP with respiratory comorbidities (76%), as well as in candidates for revision surgery (66%). CONCLUSION: Spanish otorhinolaryngologists showed a trend toward incorporating CRSwNP guideline recommendations in their clinical practice. The observed low uptake of patient-reported outcomes and objective clinical evaluation tools in routine clinical practise have been identified as areas for optimizing the management of patients with CRSwNP.


Assuntos
Pólipos Nasais , Rinite , Rinossinusite , Sinusite , Humanos , Pólipos Nasais/complicações , Pólipos Nasais/diagnóstico , Pólipos Nasais/cirurgia , Qualidade de Vida , Espanha/epidemiologia , Estudos Transversais , Rinite/complicações , Rinite/diagnóstico , Rinite/cirurgia , Sinusite/complicações , Sinusite/diagnóstico , Sinusite/terapia , Doença Crônica , Inquéritos e Questionários
2.
Front Immunol ; 14: 1310211, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38250075

RESUMO

Eosinophil-related diseases represent a group of pathologic conditions with highly heterogeneous clinical presentation and symptoms ranging from mild to critical. Both systemic and localized forms of disease are typically treated with glucocorticoids. The approval of novel biologic therapies targeting the interleukin-5 pathway can help reduce the use of systemic glucocorticoids (SGC) in eosinophilic diseases and reduce the risk of SGC-related adverse effects (AEs). In this article, a panel of experts from different medical specialties reviewed current evidence on the use of SGC in two systemic eosinophilic diseases: Eosinophilic Granulomatosis with PolyAngiitis (EGPA) and HyperEosinophilic Syndrome (HES); and in two single-organ (respiratory) eosinophilic diseases: Chronic RhinoSinusitis with Nasal Polyps (CRSwNP) and Severe Asthma with Eosinophil Phenotype (SA-EP), and contrasted it with their experience in clinical practice. Using nominal group technique, they reached consensus on key aspects related to the dose and tapering of SGC as well as on the initiation of biologics as SGC-sparing agents. Early treatment with biologics could help prevent AEs associated with medium and long-term use of SGC.


Assuntos
Produtos Biológicos , Síndrome de Churg-Strauss , Granulomatose com Poliangiite , Transtornos Leucocíticos , Humanos , Glucocorticoides/efeitos adversos , Consenso , Eosinófilos
3.
J Med Chem ; 63(9): 4732-4748, 2020 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-32275415

RESUMO

Screening of a GSK-proprietary library against intracellular Mycobacterium tuberculosis identified 1, a thioalkylbenzoxazole hit. Biological profiling and mutant analysis revealed that this compound is a prodrug that is bioactivated by the mycobacterial enzyme MymA. A hit-expansion program including design, synthesis, and profiling of a defined set of analogues with optimized drug-like properties led to the identification of an emerging lead compound, displaying potency against intracellular bacteria in the low micromolar range, high in vitro solubility and permeability, and excellent microsomal stability.


Assuntos
Antituberculosos/farmacologia , Proteínas de Bactérias/metabolismo , Benzoxazóis/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Oxigenases/metabolismo , Pró-Fármacos/farmacologia , Animais , Antituberculosos/síntese química , Antituberculosos/metabolismo , Benzoxazóis/síntese química , Benzoxazóis/metabolismo , Linhagem Celular Tumoral , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Microssomos Hepáticos/efeitos dos fármacos , Estrutura Molecular , Pró-Fármacos/síntese química , Pró-Fármacos/metabolismo , Relação Estrutura-Atividade
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