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1.
Nat Commun ; 13(1): 3321, 2022 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-35680890

RESUMO

This study investigates how specific members of the lung microbiome influence the early immune response to infection. Prevotella species are a major component of the endogenous airway microbiota. Increased abundance of Prevotella melaninogenica correlates with reduced infection with the bacterial pathogen Streptococcus pneumoniae, indicating a potentially beneficial role. Here, we show that P. melaninogenica enhances protection against S. pneumoniae, resulting in rapid pathogen clearance from the lung and improved survival in a mouse lung co-infection model. This response requires recognition of P. melaninogenica lipoproteins by toll-like receptor (TLR)2, the induction of TNFα, and neutrophils, as the loss of any of these factors abrogates Prevotella-induced protection. Improved clearance of S. pneumoniae is associated with increased serine protease-mediated killing by lung neutrophils and restraint of P. melaninogenica-induced inflammation by IL-10 in co-infected mice. Together, these findings highlight innate immune priming by airway Prevotella as an important protective feature in the respiratory tract.


Assuntos
Streptococcus pneumoniae , Receptor 2 Toll-Like , Animais , Modelos Animais de Doenças , Pulmão , Camundongos , Camundongos Endogâmicos C57BL , Ativação de Neutrófilo , Neutrófilos , Prevotella
2.
Ann Otol Rhinol Laryngol ; 129(11): 1135-1143, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32486832

RESUMO

BACKGROUND: Recommendations regarding head and neck paragangliomas (HNPGL) have undergone a fundamental reorientation in the last decade as a result of increased understanding of the genetic and pathophysiologic basis of these disorders. OBJECTIVE: We aim to provide an overview of HNPGL and recent discoveries regarding their molecular genetics, along with updated recommendations on workup, treatment, and surveillance, and their implications for otolaryngologists treating patients with these disorders. RESULTS: SDHx susceptibility gene mutations, encoding subunits of the enzyme succinate dehydrogenase (SDH), give rise to the Hereditary Pheochromocytoma/Paraganglioma Syndromes. SDHA, SDHB, SDHC, SDHD, and SDHAF2 mutations each result in unique phenotypes with distinct penetrance and risk for variable tumor development as well as metastasis. Genetic and biochemical testing is recommended for every patient with HNPGL. Multifocal disease should be managed in multi-disciplinary fashion. Patients with SDHx mutations require frequent biochemical screening and whole-body imaging, as well as lifelong follow-up with an expert in hereditary pheochromocytoma and paraganglioma syndromes. CONCLUSION: Otolaryngologists are likely to encounter patients with HNPGL. Keeping abreast of the latest recommendations, especially regarding genetic testing, workup for additional tumors, multi-disciplinary approach to care, and need for lifelong surveillance, will help otolaryngologists appropriately care for these patients.


Assuntos
Neoplasias de Cabeça e Pescoço/genética , Proteínas de Membrana/genética , Mutação , Otorrinolaringologistas , Paraganglioma/genética , Testes Genéticos , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Proteínas de Membrana/metabolismo , Paraganglioma/metabolismo , Fenótipo
3.
Laryngoscope ; 128(10): 2261-2267, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29417586

RESUMO

OBJECTIVE: To review experience, safety, and cost of office-based esophageal dilation in patients with history of head and neck cancer (HNCA). METHODS: The medical records of patients undergoing esophageal dilation in the office were retrospectively reviewed between August 2015 and May 2017. Patients were given nasal topical anesthesia. Next, a transnasal esophagoscopy (TNE) was performed. If the patient tolerated TNE, we proceeded with esophageal dilation using Seldinger technique with the CRE™ Boston Scientific (Boston Scientific Corp., Marlborough, MA) balloon system. Patients were discharged directly from the outpatient clinic. RESULTS: Forty-seven dilations were performed in 22 patients with an average of 2.1 dilations/patient (range 1-10, standard deviation [SD] ± 2.2). Seventeen patients (77%) were male. The average age was 67 years (range 35-78 years, SD ± 8.5). The most common primary site of cancer was oral cavity/oropharynx (n = 10), followed by larynx (n = 6). All patients (100%) had history of radiation treatment. Four patients were postlaryngectomy. The indication for esophageal dilation was esophageal stricture and progressive dysphagia. All dilations occurred in the proximal esophagus. There were no major complications. Three focal, superficial lacerations occurred. Two patients experienced mild, self-limited epistaxis. One dilation was poorly tolerated due to discomfort. One patient required pain medication postprocedure. Office-based esophageal dilation generated $15,000 less in health system charges compared to traditional operating room dilation on average per episode of care. CONCLUSION: In patients with history of HNCA and radiation, office-based TNE with esophageal dilation appears safe, well-tolerated, and cost-effective. In a small cohort, the technique has low complication rate and is feasible in an otolaryngology outpatient office setting. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:2261-2267, 2018.


Assuntos
Transtornos de Deglutição/cirurgia , Dilatação/métodos , Estenose Esofágica/cirurgia , Esofagoscopia/métodos , Neoplasias de Cabeça e Pescoço/complicações , Adulto , Idoso , Procedimentos Cirúrgicos Ambulatórios/efeitos adversos , Procedimentos Cirúrgicos Ambulatórios/economia , Procedimentos Cirúrgicos Ambulatórios/métodos , Custos e Análise de Custo , Transtornos de Deglutição/etiologia , Dilatação/efeitos adversos , Dilatação/economia , Estenose Esofágica/etiologia , Esofagoscopia/efeitos adversos , Esofagoscopia/economia , Esôfago/patologia , Esôfago/cirurgia , Estudos de Viabilidade , Feminino , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
4.
J Pediatr ; 188: 96-102.e1, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28669608

RESUMO

OBJECTIVE: To evaluate postnatal lung volume in infants with congenital diaphragmatic hernia (CDH) and determine if a compensatory increase in lung volume occurs during the postnatal period. STUDY DESIGN: Using a novel pulmonary magnetic resonance imaging method for imaging neonatal lungs, the postnatal lung volumes in infants with CDH were determined and compared with prenatal lung volumes obtained via late gestation magnetic resonance imaging. RESULTS: Infants with left-sided CDH (2 mild, 9 moderate, and 1 severe) were evaluated. The total lung volume increased in all infants, with the contralateral lung increasing faster than the ipsilateral lung (mean ± SD: 4.9 ± 3.0 mL/week vs 3.4 ± 2.1 mL/week, P = .005). In contrast to prenatal studies, the volume of lungs of infants with more severe CDH grew faster than the lungs of infants with more mild CDH (Spearman's ρ=-0.086, P = .01). Although the contralateral lung volume grew faster in both mild and moderate groups, the majority of total lung volume growth in moderate CDH came from increased volume of the ipsilateral lung (42% of total lung volume increase in the moderate group vs 32% of total lung volume increase in the mild group, P = .09). Analysis of multiple clinical variables suggests that increased weight gain was associated with increased compensatory ipsilateral lung volume growth (ρ = 0.57, P = .05). CONCLUSIONS: These results suggest a potential for postnatal catch-up growth in infants with pulmonary hypoplasia and suggest that weight gain may increase the volume growth of the more severely affected lung.


Assuntos
Hérnias Diafragmáticas Congênitas/fisiopatologia , Pulmão/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Pulmão/crescimento & desenvolvimento , Medidas de Volume Pulmonar/métodos , Masculino , Gravidez
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