RESUMO
Thymocyte selection-associated high-mobility group box (TOX) is a transcription factor that is crucial for T cell exhaustion during chronic antigenic stimulation, but its role in inflammation is poorly understood. Here, we report that TOX extracellularly mediates drastic inflammation upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by binding to the cell surface receptor for advanced glycation end-products (RAGE). In various diseases, including COVID-19, TOX release was highly detectable in association with disease severity, contributing to lung fibroproliferative acute respiratory distress syndrome (ARDS). Recombinant TOX-induced blood vessel rupture, similar to a clinical signature in patients experiencing a cytokine storm, further exacerbating respiratory function impairment. In contrast, disruption of TOX function by a neutralizing antibody and genetic removal of RAGE diminished TOX-mediated deleterious effects. Altogether, our results suggest an insight into TOX function as an inflammatory mediator and propose the TOX-RAGE axis as a potential target for treating severe patients with pulmonary infection and mitigating lung fibroproliferative ARDS.
Assuntos
COVID-19 , Receptor para Produtos Finais de Glicação Avançada , SARS-CoV-2 , Humanos , Receptor para Produtos Finais de Glicação Avançada/metabolismo , COVID-19/imunologia , COVID-19/metabolismo , COVID-19/patologia , COVID-19/complicações , COVID-19/virologia , Animais , Camundongos , Inflamação/metabolismo , Inflamação/patologia , Síndrome do Desconforto Respiratório/imunologia , Síndrome do Desconforto Respiratório/metabolismo , Síndrome do Desconforto Respiratório/patologia , Síndrome do Desconforto Respiratório/virologia , Lesão Pulmonar/imunologia , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Proteínas de Grupo de Alta Mobilidade/metabolismo , Proteínas de Grupo de Alta Mobilidade/genética , Masculino , Pulmão/patologia , Pulmão/metabolismo , Pulmão/imunologia , FemininoRESUMO
Investigating cholesterol trafficking pathways continues to be of significant scientific interest owing to its homeostasis being associated with several debilitating cardiovascular and neurodegenerative diseases including atherosclerosis, Niemann-Pick's disease, Alzheimer's disease, and Parkinson's disease. To further our understanding of cholesterol trafficking, it is imperative to develop new fluorescent probes that possess improved photostability, low efflux, and high spatial and temporal resolution for live-cell imaging. In this study, we developed a photoconvertible fluorescent cholesterol analog, Duo-Chol, enabling the improved spatiotemporal fluorescence imaging of the dynamic localization of cholesterol in live cells. This tool provides a unique and powerful approach to interrogating cholesterol dynamics, addressing the limitations of existing methods, and expanding our ability to probe the biological role of sterols in living cells.
Assuntos
Colesterol , Corantes Fluorescentes , Colesterol/análise , Colesterol/química , Colesterol/metabolismo , Humanos , Corantes Fluorescentes/química , Imagem Óptica/métodosRESUMO
BACKGROUND: Remimazolam is safe and effective for moderate sedation during flexible bronchoscopy, but its safety and efficacy during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) remains undetermined. The REST trial (NCT06275594) will be a prospective randomized study of remimazolam in patients undergoing EBUS-TBNA with conscious sedation. The primary aim is to evaluate whether remimazolam is safe and effective for moderate sedation during EBUS-TBNA compared to real-world midazolam and on-label midazolam. METHODS: The REST trial will recruit 330 patients from four university hospitals with mediastinal lesions suspected of being lung cancer who are eligible for EBUS-TBNA under moderate sedation. The participants will be randomized into groups using remimazolam, real-world midazolam, and on-label midazolam (US prescribing information dosage) to perform EBUS-TBNA for procedural sedation. The primary endpoint will be procedural success using composite measures. DISCUSSION: The REST trial will prospectively evaluate the efficacy and safety of remimazolam during EBUS-TBNA under moderate sedation. It will provide information for optimizing sedation modalities and contribute to practical benefits in patients undergoing EBUS-TBNA. TRIAL REGISTRATION: ClinicalTrials.gov (NCT06275594). Prospectively registered on 15 February 2024.
Assuntos
Sedação Consciente , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Hipnóticos e Sedativos , Neoplasias Pulmonares , Midazolam , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Benzodiazepinas , Broncoscopia/métodos , Broncoscopia/efeitos adversos , Sedação Consciente/métodos , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/efeitos adversos , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Hipnóticos e Sedativos/administração & dosagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Midazolam/administração & dosagem , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Global Lung Function Initiative (GLI)-2012 reference equation is currently suggested for interpretation of spirometry results and a new local reference equation has been developed in South Korea. However, lung function profiles according to the different reference equations and their clinical relevance have not been identified in chronic obstructive pulmonary disease (COPD) patients. METHODS: Our cross-sectional study evaluated Choi's, Korean National Health and National Examination Survey (KNHANES)-VI, and GLI-2012 reference equations. We estimated the percentages of predictive forced expiratory volume in one second (FEV1) and airflow limitation severity according to reference equations and analyzed their associations with patient reported outcomes (PROs): COPD assessment test (CAT) score, St. George's Respiratory Questionnaire for COPD patients (SGRQ-C) score, and six minute walk distance (6MWD). RESULTS: In the eligible 2,180 COPD patients, lower predicted values of FEV1 and forced vital capacity (FVC) were found in GLI-2012 compared to Choi's and KNHANES-VI equations. GLI-2012 equation resulted in a lower proportion of patients being classified as FEV1 < 80% or FVC < 80% compared to the other equations. However, the Z-scores of FEV1 and FVC were similar between the KNHANES-VI and GLI-2012 equations. Three reference equations exhibited significant associations between FEV1 (%) and patient-reported outcomes (CAT score, SGRQ-C score, and 6MWD). CONCLUSION: GLI-2012 reference equation may not accurately reflect FEV1 (%) in the Korean population, but the Z-score using GLI-2012 equation can be a viable option for assessing FEV1 and airflow limitation in COPD patients. Similar to the other two equations, the GLI-2012 equation demonstrated significant associations with PROs.
Assuntos
Relevância Clínica , Doença Pulmonar Obstrutiva Crônica , Humanos , Estudos Transversais , Valores de Referência , Pulmão , Espirometria , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Volume Expiratório Forçado , Capacidade VitalRESUMO
BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for chronic obstructive pulmonary disease (COPD) recommend considering patient preference when choosing an inhaler device. However, few studies have assessed both inhaler satisfaction and factors associated with high inhaler satisfaction. Therefore, we assessed inhaler satisfaction and determinants of high satisfaction in Korean COPD patients. METHODS: COPD patients were prospectively enrolled from January 2018 to November 2019. The 308 inhalers used by the 261 participants in this study included dry powder inhalers (Turbuhaler, Breezhaler, Ellipta, Diskus, and Genuair), a soft mist inhaler (Respimat), and pressurized metered dose inhalers (pMDIs). Inhaler satisfaction was assessed by the Feeling of Satisfaction with Inhaler (FSI-10) questionnaire. High inhaler satisfaction was defined as an FSI-10 ≥ 43. RESULTS: Among 261 COPD patients, 163 (62.5%) were highly satisfied with their inhaler device. The rates of high inhaler satisfaction for Turbuhaler, Breezhaler, Ellipta, Diskus, Genuair, Respimat, and pMDI usage were 40.0%, 67.2%, 66.7%, 50.0%, 55.6%, 63.4%, and 45.0%, respectively (P = 0.215). In univariate analyses, higher body mass index, non-current smoker, GOLD grades I and II, a modified Medical Research Council (mMRC) score < 2, lower inhaler puff burden, once daily usage of inhaler, and good inhaler adherence were associated with high inhaler satisfaction. In multivariate analyses, an mMRC score < 2, and good inhaler adherence were independently associated with high inhaler satisfaction. CONCLUSION: High inhaler satisfaction was associated with dyspnea symptom and good inhaler adherence in COPD patients. Effective strategies are needed including appropriate inhaler device selection, consideration of patient preference, and repeated inhaler education to improve patient satisfaction of inhalers.
Assuntos
Satisfação do Paciente , Doença Pulmonar Obstrutiva Crônica , Humanos , Desenho de Equipamento , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Nebulizadores e Vaporizadores , Inaladores de Pó Seco , República da Coreia , Administração por Inalação , Broncodilatadores/uso terapêuticoRESUMO
BACKGROUND: The presence of the bronchus sign on chest computed tomography is associated with an increased diagnostic yield of radial probe endobronchial ultrasound-guided transbronchial lung biopsy (RP-EBUS-TBLB). However, the utility of RP-EBUS-TBLB for bronchus sign negative peripheral pulmonary lesions (PPLs) remains unknown. We investigated the utility of RP-EBUS-TBLB in bronchus sign negative PPLs. METHODS: We retrospectively reviewed data from 109 patients who underwent RP-EBUS for bronchus sign negative PPLs from January 2019 to August 2020. TBLB was performed using RP-EBUS with a guide sheath and without fluoroscopy. The EBUS visualization and TBLB diagnostic yields were assessed. Multivariable logistic regression analyses were used to identify factors affecting the EBUS visualization and diagnostic yields. RESULTS: The EBUS visualization yield was 74.1% (68/109). Of the 109 lung lesions, 92 were definitively diagnosed. The overall diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 50.5% (55/109), 34.9% (29/83), 100% (26/26), 100% (29/29), and 32.5% (26/80), respectively. In multivariable analyses, the size of the lesion (≥ 20 mm; odds ratio [OR], 2.62; 95% confidence interval [CI], 1.16-5.93; P = 0.021) and the distance from the pleura (> 10 mm; OR, 2.37; 95% CI, 1.02-5.52; P = 0.045) were associated with EBUS visualization. Regarding diagnostic yield, having the probe within the lesion (OR, 28.50; 95% CI, 6.26-129.85; P < 0.001) and a solid lesion (OR, 14.58; 95% CI, 2.64-80.38; P = 0.002) were associated with diagnostic success. Pneumothorax and hemoptysis occurred in 3.7% (4/109) and 0.9% (1/109), respectively, of the patients. CONCLUSION: RP-EBUS-TBLB using a GS can be considered a diagnostic method in bronchus sign negative solid PPLs. Having the probe within the lesion and a solid lesion were important for diagnostic success. Complication rates were acceptable.
Assuntos
Biópsia/métodos , Broncoscopia/métodos , Endossonografia/instrumentação , Endossonografia/métodos , Neoplasias Pulmonares/patologia , Pulmão/patologia , Nódulos Pulmonares Múltiplos/patologia , Ultrassonografia de Intervenção/métodos , Adulto , Idoso , Biópsia/instrumentação , Brônquios/patologia , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Valor Preditivo dos Testes , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodosRESUMO
BACKGROUND: It is difficult to distinguish subtle differences shown in computed tomography (CT) images of coronavirus disease 2019 (COVID-19) and bacterial pneumonia patients, which often leads to an inaccurate diagnosis. It is desirable to design and evaluate interpretable feature extraction techniques to describe the patient's condition. METHODS: This is a retrospective cohort study of 170 confirmed patients with COVID-19 or bacterial pneumonia acquired at Yeungnam University Hospital in Daegu, Korea. The Lung and lesion regions were segmented to crop the lesion into 2D patches to train a classifier model that could differentiate between COVID-19 and bacterial pneumonia. The K-means algorithm was used to cluster deep features extracted by the trained model into 20 groups. Each lesion patch cluster was described by a characteristic imaging term for comparison. For each CT image containing multiple lesions, a histogram of lesion types was constructed using the cluster information. Finally, a Support Vector Machine classifier was trained with the histogram and radiomics features to distinguish diseases and severity. RESULTS: The 20 clusters constructed from 170 patients were reviewed based on common radiographic appearance types. Two clusters showed typical findings of COVID-19, with two other clusters showing typical findings related to bacterial pneumonia. Notably, there is one cluster that showed bilateral diffuse ground-glass opacities (GGOs) in the central and peripheral lungs and was considered to be a key factor for severity classification. The proposed method achieved an accuracy of 91.2% for classifying COVID-19 and bacterial pneumonia patients with 95% reported for severity classification. The CT quantitative parameters represented by the values of cluster 8 were correlated with existing laboratory data and clinical parameters. CONCLUSION: Deep chest CT analysis with constructed lesion clusters revealed well-known COVID-19 CT manifestations comparable to manual CT analysis. The constructed histogram features improved accuracy for both diseases and severity classification, and showed correlations with laboratory data and clinical parameters. The constructed histogram features can provide guidance for improved analysis and treatment of COVID-19.
Assuntos
COVID-19/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Pneumonia Bacteriana/diagnóstico por imagem , Síndrome do Desconforto Respiratório/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Idoso , Algoritmos , Inteligência Artificial , Análise por Conglomerados , Aprendizado Profundo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reconhecimento Automatizado de Padrão , Reprodutibilidade dos Testes , República da Coreia/epidemiologia , Síndrome do Desconforto Respiratório/complicações , Estudos Retrospectivos , Índice de Gravidade de Doença , Máquina de Vetores de SuporteRESUMO
BACKGROUND: The case fatality rate of coronavirus disease 2019 (COVID-19) is estimated to be between 4.3% and 11.0%. Currently there is no effective antiviral treatment for COVID-19. Thus, early recognition of patients at high risk is important. METHODS: We performed a retrospective observational study of 110 patients with severe acute respiratory syndrome coronavirus 2 infection. We compared the effectiveness of three scoring systems: the Systemic Inflammatory Response Syndrome (SIRS), quick Sequential Organ Failure Assessment (qSOFA), and National Early Warning Score (NEWS) systems, for predicting the prognosis of COVID-19. The area under the receiver operating characteristic curve (AUROC) was used for these assessments, and Kaplan-Meier survival curves were used to identify the cumulative risk for 28-day mortality according to the NEWS stratification. RESULTS: For predicting 28-day mortality, NEWS was superior to qSOFA (AUROC, 0.867 vs. 0.779, P < 0.001), while there was no significant difference between NEWS and SIRS (AUROC, 0.867 vs. 0.639, P = 0.100). For predicting critical outcomes, NEWS was superior to both SIRS (AUROC, 0.918 vs. 0.744, P = 0.032) and qSOFA (AUROC, 0.918 vs. 0.760, P = 0.012). Survival time was significantly shorter for patients with NEWS ≥ 7 than for patients with NEWS < 7. CONCLUSION: Calculation of the NEWS at the time of hospital admission can predict critical outcomes in patients with COVID-19. Early intervention for high-risk patients can thereby improve clinical outcomes in COVID-19 patients.
Assuntos
Deterioração Clínica , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Insuficiência de Múltiplos Órgãos/diagnóstico , Escores de Disfunção Orgânica , Pneumonia Viral/diagnóstico , Pneumonia Viral/mortalidade , Idoso , Betacoronavirus , COVID-19 , Infecções por Coronavirus/patologia , Diagnóstico Precoce , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/patologia , Prognóstico , Estudos Retrospectivos , SARS-CoV-2RESUMO
BACKGROUND: Since its first detection in December 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 infection has spread rapidly around the world. Although there have been several studies investigating prognostic factors for severe COVID-19, there have been no such studies in Korea. METHODS: We performed a retrospective observational study of 110 patients with confirmed COVID-19 hospitalized at a tertiary hospital in Daegu, Korea. Demographic, clinical, laboratory, and outcome data were collected and analyzed. Severe disease was defined as a composite outcome of acute respiratory distress syndrome, intensive care unit care, or death. RESULTS: Diabetes mellitus (odds ratio [OR], 19.15; 95% confidence interval [CI], 1.90-193.42; P = 0.012), body temperature ≥ 37.8°C (OR, 10.91; 95% CI, 1.35-88.36; P = 0.025), peripheral oxygen saturation < 92% (OR, 33.31; 95% CI, 2.45-452.22; P = 0.008), and creatine kinase-MB (CK-MB) > 6.3 (OR, 56.84; 95% CI, 2.64-1,223.78, P = 0.010) at admission were associated with higher risk of severe COVID-19. The likelihood of development of severe COVID-19 increased with an increasing number of prognostic factors. CONCLUSION: In conclusion, we found that diabetes mellitus, body temperature ≥ 37.8°C, peripheral oxygen saturation < 92%, and CK-MB > 6.3 are independent predictors of severe disease in hospitalized COVID-19 patients. Appropriate assessment of prognostic factors and close monitoring to provide the necessary interventions at the appropriate time in high-risk patients may reduce the case fatality rate of COVID-19.
Assuntos
Infecções por Coronavirus/patologia , Complicações do Diabetes/virologia , Diabetes Mellitus/patologia , Febre/patologia , Hipóxia/patologia , Pneumonia Viral/patologia , Adolescente , Adulto , Idoso , Betacoronavirus , COVID-19 , Criança , Pré-Escolar , Feminino , Hospitalização , Humanos , Lactente , Recém-Nascido , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Pandemias , Prognóstico , República da Coreia , Síndrome do Desconforto Respiratório/etiologia , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Adulto JovemRESUMO
Purpose: The use of inhaled bronchodilators is the mainstay of treatment for patients with chronic obstructive pulmonary disease (COPD). Although the soft mist inhaler (SMI) was developed to overcome the disadvantages of pressurized metered dose and drug powder inhalers, misuse during handling has been frequently observed in many studies. However, few studies have focused on SMI misuse among patients with COPD. Thus, we aimed to assess and identify the risk factors associated with SMI misuse among patients with COPD. Patient and Methods: In this prospective, observational, cross-sectional study, we enrolled patients with COPD who were undergoing SMI treatment between January 2018 and March 2020. An advanced nurse practitioner assessed the participants' handling of the device by using a check list. Results: Among 159 participants, 136 (85.5%) reported inhaler misuse. Duration of COPD and COPD assessment test (CAT) scores were positively associated with inhaler misuse; adherence and education level were negatively associated with inhaler misuse. In the multivariable analysis, a low educational level (less than high school), high CAT score (≥ 10), and short duration of COPD (≤ 2 years) were identified as risk factors for SMI misuse. Conclusion: SMI misuse remains common among patients with COPD. Therefore, clinicians should pay close attention to their patients using SMIs, especially in the early period after the diagnosis of COPD.
Assuntos
Broncodilatadores , Nebulizadores e Vaporizadores , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Masculino , Feminino , Estudos Transversais , Fatores de Risco , Idoso , Estudos Prospectivos , Pessoa de Meia-Idade , Broncodilatadores/administração & dosagem , Broncodilatadores/efeitos adversos , Administração por Inalação , Adesão à Medicação , Desenho de Equipamento , Medição de Risco , Escolaridade , Pulmão/fisiopatologia , Pulmão/efeitos dos fármacosRESUMO
Diagnosing ground-glass opacity (GGO) pulmonary lesions poses challenges. This study evaluates the utility of radial probe endobronchial ultrasound-guided transbronchial lung biopsy (RP-EBUS-TBLB) in diagnosing GGO pulmonary lesions. A total of 1651 RP-EBUS procedures were performed during the study period. This study analyzed 115 GGO lesions. The EBUS visualization yield was 80.1%. Of 115 lesions, 69 (60%) were successfully diagnosed. The average size of diagnosed lesions was significantly larger than that of undiagnosed lesions (21.9 ± 7.3 vs. 17.1 ± 6.6 mm, p < 0.001). Diagnostic yield varied by lesion size: 50.0% for lesions <20 mm, 65.1% for 20-30 mm lesions, and 85.7% for lesions >30 mm. The mixed blizzard sign on EBUS appeared in 60.6% of mixed GGO lesions, with no cases in pure GGO lesions. Multivariable analyses showed that lesion size (odds ratio [OR], 1.10; 95% confidence interval [CI], 1.00-1.16; p < 0.001) and mixed blizzard sign on EBUS (OR, 20.92; CI, 7.50-58.31; p < 0.001) were significantly associated with diagnostic success. Pneumothorax and hemoptysis occurred in 1.7% and 2.6% of patients, respectively. RP-EBUS-TBLB without fluoroscopic guidance is a viable diagnostic approach for GGO pulmonary lesions with acceptable complications.
RESUMO
BACKGROUND: The PACIFIC trial demonstrated survival benefit of durvalumab after concurrent chemoradiotherapy (CCRT) in unresectable stage III non-small-cell lung cancer. Data on the effectiveness and safety of durvalumab in elderly patients is lacking. METHODS: This retrospective study was conducted between September 2017 and September 2022. Progression-free survival (PFS), overall survival (OS), recurrence patterns, first subsequent treatment after recurrence, factors associated with survival outcomes, and adverse events (AEs) were compared. RESULTS: Of the 286 patients, 120 (42.0%) were ≥ 70 years and 166 (58.0%) were < 70 years. The median PFS (17.7 vs. 19.4 months; P = .43) and median OS (35.7 months vs. not reached; P = .13) were similar between 2 groups. Proportion of patients who completed durvalumab was lower in elderly patients (27.5% vs. 39.2%; P = .040). In elderly patients, ECOG PS 0 or 1 was associated with better PFS, and being male and having received a cisplatin-based regimen during CCRT were factors associated with better and worse OS, respectively. In patients aged < 70 years, a PD-L1 ≥ 50% was associated with improved PFS and OS. Elderly patients experienced more treatment-related AEs, grade 3/4 AEs, permanent discontinuation of durvalumab, and treatment-related deaths. Among the AEs leading to permanent discontinuation or death, pulmonary AE was significantly more common in elderly patients. CONCLUSION: Durvalumab demonstrated similar outcomes in elderly compared to younger patients. However, AEs were more common in elderly patients. Thus, judicious selection of patients and chemotherapy regimens, coupled with careful AE monitoring, are important factors for ensuring optimal durvalumab treatment.
Assuntos
Anticorpos Monoclonais , Carcinoma Pulmonar de Células não Pequenas , Quimiorradioterapia , Neoplasias Pulmonares , Estadiamento de Neoplasias , Humanos , Masculino , Feminino , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Estudos Retrospectivos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/mortalidade , Quimiorradioterapia/métodos , Anticorpos Monoclonais/uso terapêutico , Pessoa de Meia-Idade , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Idoso de 80 Anos ou mais , Taxa de Sobrevida , Quimioterapia de ConsolidaçãoRESUMO
BACKGROUND: Few studies assessed the use of endobronchial ultrasound (EBUS)-guided re-biopsy for detecting the T790M mutation after epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) failure. METHODS: A total of 2996 EBUS procedures were performed during the study period (January 2019-June 2022). In total, 44 consecutive patients who underwent EBUS-guided re-biopsy (56 procedures) for detecting the T790M mutation were analyzed. The success rates and T790M mutation frequencies were analyzed according to the re-biopsy site and EBUS method. Multivariate logistic regression analyses were used to identify factors affecting the likelihood of the T790M mutation. RESULTS: The success rates for the mutation analyses using EBUS with a guide-sheath (EBUS-GS), EBUS guided transbronchial needle aspiration (EBUS-TBNA), and EBUS-GS with EBUS-TBNA for re-biopsy were 80.6% (29/36), 93.3% (14/15), and 100% (5/5), respectively. Patients who underwent lymph node biopsy using EBUS-TBNA had an increased rates of the T790M mutation compared with those undergoing lung biopsy using EBUS-GS (EBUS-TBNA, 60.0%; EBUS-GS with EBUS-TBNA, 40.0%; EBUS-GS, 11.1%; p < 0.001). In multivariate analysis, the use of a first-generation EGFR-TKI (odds ratio [OR], 4.29; 95% confidence interval [CI], 1.05-17.58; p = 0.043) was associated with occurrence of the T790M mutation. Re-biopsy of the metastatic site tended to be associated with a higher T790M mutation rate. Mild hemoptysis occurred in 3.6% (2/56) of the patients. CONCLUSIONS: EBUS-guided re-biopsy can be used for detecting the T790M mutation in patients who failed EGFR-TKI therapy. The T790M mutation frequency differed according to the re-biopsy site. The use of a first-generation EGFR-TKI was an independent predictor of the T790M mutation.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/diagnóstico , Receptores ErbB/genética , Mutação , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Biópsia Guiada por Imagem/métodos , Estudos Retrospectivos , Ultrassonografia de Intervenção , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Broncoscopia/métodosRESUMO
BACKGROUND: Poor pulmonary function and chronic obstructive pulmonary disease (COPD) are associated with poorer overall survival (OS) in non-small-cell lung cancer (NSCLC) patients. Few studies have investigated the association between pulmonary function and OS in small-cell lung cancer (SCLC) patients. We compared the clinical characteristics of extensive disease SCLC (ED-SCLC) with or without moderately impaired diffusion capacity for carbon monoxide (DLco) and investigated the factors associated with survival in ED-SCLC patients. METHODS: This retrospective single-center study was performed between January 2011 and December 2020. Of the 307 SCLC patients who received cancer therapy during the study, 142 with ED-SCLC were analyzed. The patients were divided into DLco < 60% group and DLco ≥ 60% groups. OS and predictors of poor OS were analyzed. RESULTS: The median OS of the 142 ED-SCLC patients was 9.3 months and the median age was 68 years. In total, 129 (90.8%) patients had a history of smoking, and 60 (42.3%) had COPD. Thirty-five (24.6%) patients were assigned to the DLco < 60% group. Multivariate analysis revealed that DLco < 60% (odds ratio [OR], 1.609; 95% confidence interval [CI], 1.062-2.437; P = 0.025), number of metastases (OR, 1.488; 95% CI, 1.262-1.756; P < 0.001), and < 4 cycles of first-line chemotherapy (OR, 3.793; 95% CI, 2.530-5.686; P < 0.001) were associated with poor OS. Forty (28.2%) patients received < 4 cycles of first-line chemotherapy; the most common reason for this was death (n = 22, 55%) from grade 4 febrile neutropenia (n = 15), infection (n = 5), or massive hemoptysis (n = 2). The DLco < 60% group had a shorter median OS than the DLco ≥ 60% group (10.6 ± 0.8 vs. 4.9 ± 0.9 months, P = 0.003). CONCLUSIONS: In this study, approximately one quarter of the ED-SCLC patients had DLco < 60%. Low DLco (but not forced expiratory volume in 1 s or forced vital capacity), a large number of metastases, and < 4 cycles of first-line chemotherapy were independent risk factors for poor survival outcomes in patients with ED-SCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Doença Pulmonar Obstrutiva Crônica , Carcinoma de Pequenas Células do Pulmão , Humanos , Idoso , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Neoplasias Pulmonares/patologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/complicações , Estudos Retrospectivos , PrognósticoRESUMO
OBJECTIVE: Impaired lung function is associated with an increased risk for cognitive decline. F-18 fluorodeoxyglucose (FDG) PET is a well-known neurodegenerative biomarker for dementia. We investigated the association between lung and brain function using FDG PET in patients with lung cancer. METHODS: A random sub-sample of 102 patients with lung cancer and without a self-reported history of neuropsychiatric disorders were recruited and underwent both lung function tests and FDG PET scans before treatment. Lung function was analyzed as the percentage predicted value (% pred) of forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1). FDG uptake was measured as standardized uptake values (SUVs) in the frontal, parietal, temporal, and occipital cortices and cognition-related regions. Regional SUV ratios (SUVRs) were calculated by dividing the SUV in each region by the whole-brain SUV and were then evaluated against lung function indices and clinical variables. RESULTS: After excluding five patients with brain metastases, 97 patients were included in the final analysis (mean age, 67.7 ± 10.3 years). Mean FVC and mean FEV1 were 80.0% ± 15.4% and 77.6% ± 17.8%, respectively. Both FVC and FEV1 were positively correlated with SUVRs in all brain regions after adjusting the data for clinical variables. The degree of decrease in SUVRs related to lung function was not significantly different between cognition-related regions and other regions. CONCLUSION: Impaired lung function was associated with decreased glucose metabolism in all regions of the brain, indicating that cognitive decline related to decreased glucose metabolism may be due to reduced perfusion.
Assuntos
Disfunção Cognitiva , Neoplasias Pulmonares , Humanos , Pessoa de Meia-Idade , Idoso , Fluordesoxiglucose F18/metabolismo , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Tomografia por Emissão de Pósitrons , Encéfalo/metabolismo , Pulmão/patologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/metabolismo , Glucose/metabolismo , Compostos Radiofarmacêuticos/uso terapêuticoRESUMO
Models trained on datasets with texture bias usually perform poorly on out-of-distribution samples since biased representations are embedded into the model. Recently, various image translation and debiasing methods have attempted to disentangle texture biased representations for downstream tasks, but accurately discarding biased features without altering other relevant information is still challenging. In this paper, we propose a novel framework that leverages image translation to generate additional training images using the content of a source image and the texture of a target image with a different bias property to explicitly mitigate texture bias when training a model on a target task. Our model ensures texture similarity between the target and generated images via a texture co-occurrence loss while preserving content details from source images with a spatial self-similarity loss. Both the generated and original training images are combined to train improved classification or segmentation models robust to inconsistent texture bias. Evaluation on five classification- and two segmentation-datasets with known texture biases demonstrates the utility of our method, and reports significant improvements over recent state-of-the-art methods in all cases.
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How ubiquitous circadian clocks orchestrate tissue-specific outputs is not well understood. Pancreatic ß cell-autonomous clocks attune insulin secretion to daily energy cycles, and desynchrony from genetic or behavioral disruptions raises type 2 diabetes risk. We show that the transcription factor DEC1, a clock component induced in adult ß cells, coordinates their glucose responsiveness by synchronizing energy metabolism and secretory gene oscillations. Dec1-ablated mice develop lifelong hypo-insulinemic diabetes, despite normal islet formation and intact circadian Clock and Bmal1 activators. DEC1, but not CLOCK/BMAL1, binds maturity-linked genes that mediate respiratory metabolism and insulin exocytosis, and Dec1 loss disrupts their transcription synchrony. Accordingly, ß-cell Dec1 ablation causes hypo-insulinemia due to immature glucose responsiveness, dampening insulin rhythms. Thus, Dec1 links circadian clockwork to the ß-cell maturation process, aligning metabolism to diurnal energy cycles.
RESUMO
Amidst attention towards improving equality, inclusivity, and diversity, citizen science is woefully anachronistic in its name. There is a critical need for this field to distance itself from the exclusionary nature of the term 'citizen'. We provide reasoning for abandoning this term and an outline for adopting a new name.