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1.
Infect Drug Resist ; 16: 3955-3963, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37361939

RESUMO

Background: Mycobacterium abscessus (M. abscessus) is a rapidly growing bacterium (RGM) that causes refractory pulmonary and extrapulmonary infections. However, studies investigating pharyngeal and laryngeal M. abscessus infections are limited. Case Presentation: A 41-year-old immunocompetent woman complaining of bloody sputum was referred to our hospital. Although her sputum culture tested positive for M. abscessus subsp. abscessus, radiological findings were not indicative of pulmonary infection or sinusitis. Further diagnostic workup, including laryngeal endoscopy and positron emission tomography/computed tomography (PET/CT), confirmed the presence of nasopharyngeal M. abscessus infection. The patient was initially treated with intravenous amikacin, imipenem/cilastatin, azithromycin, and clofazimine for 28 days, after which the patient was provided with amikacin, azithromycin, clofazimine, and sitafloxacin for four months. After the completion of antibiotic therapy, the patient showed negative results on sputum smear and culture and normal findings on PET/CT and laryngeal endoscopy. Whole-genome sequencing of this strain revealed that it belonged to the ABS-GL4 cluster, which has a functional erythromycin ribosomal methylase gene, although it is not a major lineage in non-cystic fibrosis (CF) patients in Japan and Taiwan and in CF patients in European countries. We conducted a literature review and identified seven patients who developed pharyngeal/laryngeal non-tuberculous mycobacterium (NTM) infection. Four of the eight patients had a history of immunosuppressant use, including steroids. Seven of the eight patients responded well to their treatment regimens. Conclusion: Patients whose sputum culture tests are positive for NTM and who meet the diagnostic criteria for NTM infection but do not have intrapulmonary lesions should be evaluated for otorhinolaryngological infections. Our case series revealed that immunosuppressant use is a risk factor for pharyngeal/laryngeal NTM infection and that patients with pharyngeal/laryngeal NTM infections respond relatively well to antibiotic therapy.

2.
Nature ; 609(7928): 754-760, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35940203

RESUMO

Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1-5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.


Assuntos
COVID-19 , Proteínas Ativadoras de GTPase , Estudo de Associação Genômica Ampla , Fatores de Troca do Nucleotídeo Guanina , Interações entre Hospedeiro e Microrganismos , SARS-CoV-2 , Alelos , Animais , COVID-19/complicações , COVID-19/genética , COVID-19/imunologia , COVID-19/fisiopatologia , Modelos Animais de Doenças , Proteínas Ativadoras de GTPase/antagonistas & inibidores , Proteínas Ativadoras de GTPase/genética , Proteínas Ativadoras de GTPase/metabolismo , Predisposição Genética para Doença , Fatores de Troca do Nucleotídeo Guanina/antagonistas & inibidores , Fatores de Troca do Nucleotídeo Guanina/genética , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Interações entre Hospedeiro e Microrganismos/genética , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Interferon Tipo I/genética , Interferon Tipo I/imunologia , Japão , Pulmão/patologia , Macrófagos , Mesocricetus , Pessoa de Meia-Idade , Pneumonia/complicações , Pirazóis/farmacologia , RNA-Seq , SARS-CoV-2/patogenicidade , Carga Viral , Redução de Peso
3.
Chest ; 161(4): e219-e223, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35396055

RESUMO

CASE PRESENTATION: A 70-year-old woman who had received a diagnosis of pneumonia in the right lower lobe was treated with antibiotics at a general practitioner's clinic 9 months earlier. Her pneumonia had improved, but the cough and lung infiltrates persisted for > 6 months, so the patient was referred to our hospital. She had undergone surgery for breast cancer 30 years earlier but had no other medical history. She was not taking any medications and had no history of smoking, including passive smoking.


Assuntos
Pneumonia , Idoso , Tosse , Feminino , Humanos , Pulmão , Pneumonia/diagnóstico , Pneumonia/etiologia
4.
Respir Med Case Rep ; 33: 101408, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34401256

RESUMO

Acquired immunodeficiency in thymoma (Good's syndrome) without hypogammaglobulinemia is a rare condition. Here we describe the case of a 29-year-old Japanese woman with thymoma-associated T cell immunodeficiency after radiation therapy. She was admitted to the hospital with refractory pneumonia, which resulted from as T cell immunodeficiency, as revealed through low peripheral lymphocytes and oral candidiasis triggered through radiotherapy and required long-term antimicrobial therapy. Although radiotherapy is commonly administered for thymoma, our findings suggest that physicians should consider carrying out lymphocyte counts during thymoma treatment.

5.
Kyobu Geka ; 74(2): 116-119, 2021 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-33976016

RESUMO

A 83-year-old man underwent thyroplasty with arytenoid adduction for right recurrent laryngeal nerve palsy 1 year ago. He had been suffering from hemosputum and cough for last 2 months, and was referred to our hospital for medical examination. Laryngoscopy and neck computed tomography showed subglottic nodule. No evidence of malignancy was noted by a transbronchial biopsy of subglottic nodule. Since subglottic nodule grew rapidly during 2 months observation period, subglottic nodule resection was performed by bronchoscope. Histopathologic examination revealed that the tumor was suture granuloma with no evidence of malignancy. Cervical abscess as a complication of subglottic suture granuloma resection was occurred, because of suture material for arytenoid adduction and the injury of mucous membrane for removing the granuloma with the fenestration of thyroid cartilage for thyroplasty.


Assuntos
Laringoplastia , Abscesso/diagnóstico por imagem , Abscesso/etiologia , Abscesso/cirurgia , Idoso de 80 Anos ou mais , Cartilagem Aritenoide/diagnóstico por imagem , Cartilagem Aritenoide/cirurgia , Granuloma , Humanos , Masculino , Suturas
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