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BACKGROUND: Bronchial thermoplasty (BT) is a recently developed non-pharmacological therapy for refractory bronchial asthma. Although increasing evidence has suggested that BT is effective for various phenotypes of severe asthma, its safety and efficacy in patients with severe irreversible impaired lung function are unclear. OBJECTIVES: To assess the efficacy and safety of BT in patients with refractory asthma, including patients with a severely impaired forced expiratory volume in 1 second (FEV1). DESIGN: This was a single-center, retrospective, observational cohort study. METHODS: We retrospectively reviewed the medical records of 15 patients with refractory asthma (Global Initiative for Asthma step 4 or 5), including patients with severely impaired airflow limitation (% predicted pre-bronchodilator FEV1 <60%), who had undergone BT between June 2016 and January 2022. We analyzed the efficacy (change in asthma symptoms, exacerbation rate, pulmonary function, asthma medication, and serum inflammatory chemokine/cytokines before and after BT) and complications in all patients. We compared these data between patients with severe obstructive lung dysfunction [group 1(G1)] and patients with FEV1 ⩾ 60% [group 2 (G2)]. RESULTS: Six patients were in G1 and nine were in G2. Clinical characteristics, T2 inflammation, and concurrent treatment were equivalent in both groups. BT significantly improved asthma-related symptoms (measured using the Asthma Control Test and Asthma Quality of Life Questionnaire scores) in both groups. FEV1 was significantly improved in G1 but not in G2. Four patients in G2, but none in G1, experienced asthma exacerbation requiring additional systemic corticosteroids (including two requiring prolonged hospitalization) after BT. Long-term responders (patients who reduced systemic or inhaled corticosteroid without newly adding biologics in a follow-up > 2 years) of BT were identified in G1 and G2 (n = 2, 33.3% and n = 4, 44.4%, respectively). CONCLUSION: BT in patients with refractory asthma and severe airflow limitation is equally safe and efficacious as that in patients with moderate airflow limitation.
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Asma , Termoplastia Brônquica , Pulmão , Índice de Gravidade de Doença , Humanos , Masculino , Estudos Retrospectivos , Feminino , Termoplastia Brônquica/efeitos adversos , Asma/fisiopatologia , Asma/terapia , Pessoa de Meia-Idade , Volume Expiratório Forçado , Resultado do Tratamento , Idoso , Pulmão/fisiopatologia , Adulto , Recuperação de Função Fisiológica , Fatores de Tempo , Qualidade de VidaRESUMO
INTRODUCTION: Increasing numbers of cases of mild asymptomatic pulmonary alveolar proteinosis (PAP) are being reported with the recent increase in chest computed tomography (CT). Bronchoscopic diagnosis of mild PAP is challenging because of the patchy distribution of lesions, which makes it difficult to obtain sufficient biopsy samples. Additionally, the pathological findings of mild PAP, particularly those that differ from severe PAP, have not been fully elucidated. This study aimed to clarify the pathological findings of mild PAP and the usefulness of optical biopsy using probe-based confocal laser endomicroscopy (pCLE). METHODS: We performed bronchoscopic optical biopsy using pCLE and tissue biopsy in 5 consecutive patients with PAP (three with mild PAP and two with severe PAP). We compared the pCLE images of mild PAP with those of severe PAP by integrating clinical findings, tissue pathology, and chest CT images. RESULTS: pCLE images of PAP showed giant cells with strong fluorescence, amorphous substances, and thin alveolar walls. Images of affected lesions in mild PAP were equivalent to those obtained in arbitrary lung lesions in severe cases. All 3 patients with mild PAP spontaneously improved or remained stable after ≥3 years of follow-up. Serum autoantibodies to granulocyte-macrophage colony-stimulating factor were detected in all 5 cases. CONCLUSION: Optical biopsy using pCLE can yield specific diagnostic findings, even in patients with mild PAP. pCLE images of affected areas in mild and severe PAP showed similar findings, indicating that the dysfunction level of pathogenic alveolar macrophages in affected areas is similar between both disease intensities.
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Doenças Autoimunes , Proteinose Alveolar Pulmonar , Humanos , Proteinose Alveolar Pulmonar/diagnóstico por imagem , Microscopia Confocal/métodos , Biópsia , LasersRESUMO
Induced pluripotent stem (iPS) cells are widely used as a research tool in regenerative medicine and embryology. In studies related to lens regeneration in the eye, iPS cells have been reported to differentiate into lens epithelial cells (LECs); however, to the best of our knowledge, no study to date has described their formation of three-dimensional cell aggregates. Notably, in vivo studies in newts have revealed that iris cells in the eye can dedifferentiate into LECs and regenerate a new lens. Thus, as basic research on lens regeneration, the present study investigated the differentiation of human iris tissue-derived cells and human iris tissue-derived iPS cells into LECs and their formation of three-dimensional cell aggregates using a combination of two-dimensional culture, static suspension culture and rotational suspension culture. The results revealed that three-dimensional cell aggregates were formed and differentiated into LECs expressing αA-crystallin, a specific marker protein for LECs, suggesting that the cell-cell interaction facilitated by cell aggregation may have a critical role in enabling highly efficient differentiation of LECs. However, the present study was unable to achieve transparency in the cell aggregates; therefore, we aim to continue to investigate the degradation of organelles and other materials necessary to make the interior of the formed cell aggregates transparent. Furthermore, we aim to expand on our current work to study the regeneration of the lens and ciliary body as a whole in vitro, with the aim of being able to restore focusing function after cataract surgery.
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OBJECTIVE: The prevalence of obstructive sleep apnea (OSA) in Japan is 9% among males and 3% among females. Up to 2.5 million patients are estimated to suffer from the disease, but limited number of facilities are capable of carrying out polysomnography (PSG), leaving more than 80% of these individuals are undiagnosed. In recent years, the development of new portable sleep monitoring (PMs) devices has been remarkable. We evaluate the correlation between the results of the LS-140 PMs device (Fukuda Denshi Tech Co. Ltd.), released in 2017, and those of PSG. METHODS: We obtained contemporaneous data from the same patients by equipping 58 patients with PMs (LS-140) devices while they underwent PSG. Our primary outcome was Case 2 of the intraclass correlation coefficient (ICC), i.e., the ICC (2.1). And we used a Bland-Altman analysis to compare the apnea-hypopnea index (AHI) given by PSG and the respiratory event index (REI) given by LS-140 and examined the sensitivity and specificity of the REI relative to the AHI in the diagnosis of OSA. We also carried out the same comparison but in terms of the presence or absence of periodic limb movements (PLMs). RESULTS: The ICC (2.1) between The REI and the AHI was 0.944, a rather high value (p<0.0001). The mean difference between AHI and REI values was -3.6 (p<0.0001), indicating a negative fixed bias. Sensitivity may decrease in groups with PLMs. CONCLUSION: The REI and the AHI are highly correlated, giving LS-140 sufficient diagnostic sensitivity and specificity to screen for OSA.
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BACKGROUND: Pneumothorax is one complication of transbronchial biopsy (TBB) using endobronchial ultrasonography with a guide sheath (EBUS-GS-TBB). We sought to clarify the risk factors for pneumothorax after EBUS-GS-TBB under fluoroscopic guidance. METHODS: We retrospectively reviewed data from 916 patients who underwent EBUS-GS-TBB at Fujita Health University Hospital. We evaluated the following risk factors for pneumothorax after EBUS-GS-TBB: patient characteristics (sex, age, and pulmonary comorbidities); lesion data (location, size, existence of ground-glass opacities [GGOs], pleural involvement, computed tomography [CT] bronchus sign, visibility on fluoroscopy, and EBUS findings); final diagnosis; years of bronchoscopist experience; and guide sheath size. Univariate and multivariate logistic regression analyses were performed. RESULTS: Among the 916 patients, 30 (3.28%) presented with pneumothorax. With a univariate analysis, factors that independently predisposed to pneumothorax included lesions containing GGOs, lesions in sagittal lung segments on fluoroscopy, lesions that were not visible on fluoroscopy, and infectious lesions. A univariate analysis also showed that lesions in the right upper lobe or left upper division, as well as malignant lesions, were less likely to lead to pneumothorax. Age, underlying pulmonary disease, CT bronchus sign, EBUS findings, bronchoscopist experience, and guide sheath size did not influence the incidence of pneumothorax. A multivariate analysis revealed that only lesions containing GGOs (odds ratio [OR] 6.47; 95% confidence interval [CI] 2.13-19.6, P = 0.001) and lesions in lung segments with a sagittal orientation on fluoroscopy (OR 2.47; 95% CI 1.09-5.58, P = 0.029) were significant risk factors for EBUS-GS-TBB-related pneumothorax. CONCLUSIONS: EBUS-GS-TBB of lesions containing GGOs or lesions located in sagittal lung segments on fluoroscopy correlate with a higher pneumothorax risk.
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Endossonografia/métodos , Biópsia Guiada por Imagem/efeitos adversos , Pneumopatias/patologia , Pneumotórax/etiologia , Idoso , Feminino , Fluoroscopia/efeitos adversos , Humanos , Modelos Logísticos , Masculino , Análise Multivariada , Pneumotórax/prevenção & controle , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Ultrassonografia de IntervençãoAssuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Asma Induzida por Aspirina/complicações , Celecoxib/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Doenças Respiratórias/diagnóstico , Doenças Respiratórias/etiologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Asma Induzida por Aspirina/tratamento farmacológico , Celecoxib/uso terapêutico , HumanosRESUMO
BACKGROUND: Infectious complications after endobronchial ultrasound-guided transbronchial biopsy with a guide sheath (EBUS-GS-TBB) are serious in that they may delay or change scheduled subsequent therapy. The aim of this study was to identify risk factors for infection after EBUS-GS-TBB. RESEARCH QUESTION: What are the risk factors for infection after EBUS-GS-TBB? STUDY DESIGN AND METHODS: We retrospectively reviewed the medical records of 1,045 consecutive patients who had undergone EBUS-GS-TBB for peripheral lung lesions between January 2013 and December 2017 at Fujita Health University Hospital. We evaluated the following risk factors for infectious complications after EBUS-GS-TBB: relevant patient characteristics (age and comorbidities), lesion size, CT scan features of target lesion (intratumoral low-density areas [LDAs] and cavitation), stenosis of responsible bronchus observed by bronchoscopy, and laboratory data before EBUS-GS-TBB (WBC count and C-reactive protein concentration). RESULTS: Forty-seven of the study patients developed infectious complications (24 with pneumonia, 14 with intratumoral infection, three with lung abscess, three with pleuritis, and three with empyema), among whom the complication caused a delay in cancer treatment in 13 patients, cancellation of cancer treatment in seven patients, and death in three patients. Multivariate analysis showed that cavitation (P = .007), intratumoral LDAs (P < .001), and stenosis of responsible bronchus observed by bronchoscopy (P < .001) were significantly associated with infectious complications after EBUS-GS-TBB. Prophylactic antibiotics had been administered to 13 patients in the infection group. Propensity matched analysis could not show significant benefit of prophylactic antibiotics in preventing post-EBUS-GS-TBB infections. INTERPRETATION: Cavitation, LDAs for CT scan features of target lesions, and stenosis of responsible bronchus observed by bronchoscopy are risk factors of post-EBUS-GS-TBB infection. In the cohort, prophylactic antibiotics failed to prevent infectious complications.
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Endossonografia/métodos , Biópsia Guiada por Imagem/efeitos adversos , Neoplasias Pulmonares/patologia , Infecções Respiratórias/etiologia , Ultrassonografia de Intervenção , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antibioticoprofilaxia , Broncoscopia , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Respiratórias/prevenção & controle , Estudos Retrospectivos , Fatores de RiscoAssuntos
Pólipos Nasais , Aspirina , Citocinas , Humanos , Japão , Prostaglandina D2 , Linfopoietina do Estroma do TimoRESUMO
Atopic cataracts develop under the ages of 40 years, after which visual acuity rapidly declines. However, the mechanism underlying the development of atopic cataracts is not yet clear. We focused on the eosinophil granule major basic protein (MBP), which was detected in the aqueous humor of atopic cataracts previously, and which was cytotoxic. Specifically, we investigated its origin in this fluid and its effects on lens epithelial cells (LECs). MBP immunostaining was positive in atopic cataract-derived LECs, but negative in age-related cataract-derived LECs. MBP mRNA was not detected in either type of cataract, but protein was detected in the aqueous humor. Furthermore, the flare values associated with atopic cataracts were higher than those with age-related cataracts. When MBP was purified from eosinophils or recombinant MBP was added to LEC culture medium, cell viability decreased in a concentration-dependent manner, but an MBP antibody neutralized the cytotoxic effect of this protein towards these cells. These results were consistent with the flow of MBP into the aqueous humor from the blood due to a compromised blood-aqueous barrier. Thus, MBP could further penetrate the lens capsule and adhere to LECs, resulting in decreased cell viability and the development of atopic cataracts.
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Catarata/imunologia , Proteína Básica Maior de Eosinófilos/metabolismo , Eosinófilos/metabolismo , Proteoglicanas/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Humor Aquoso/imunologia , Humor Aquoso/metabolismo , Estudos de Casos e Controles , Catarata/sangue , Catarata/patologia , Extração de Catarata , Sobrevivência Celular/imunologia , Células Cultivadas , Proteína Básica Maior de Eosinófilos/análise , Proteína Básica Maior de Eosinófilos/imunologia , Proteína Básica Maior de Eosinófilos/isolamento & purificação , Eosinófilos/imunologia , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Feminino , Humanos , Cristalino/citologia , Cristalino/imunologia , Cristalino/patologia , Cristalino/cirurgia , Masculino , Cultura Primária de Células , Proteoglicanas/análise , Proteoglicanas/imunologia , Proteoglicanas/isolamento & purificação , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Adulto JovemRESUMO
Dendritic cell-based immunotherapy, which uses a patient's own immune cells, can be used for cancer treatment and allergy control, such as autoimmune disease and rejection associated with transplantation. However, these treatments create a burden on patients due to repeated blood collection. We used cell biological analysis of monocytes with few mutations obtained from minimal blood collection for genome recombination. Next, we established human peripheral blood monocyte-derived induced pluripotent stem cells (iPSCs) using a commercial vector and standard culture method. We found that when established iPSCs were induced to differentiate, monocytes showed phagocytic properties and expressed CD14 and CX3CR1. Further, the generated dendritic cells (DCs) expressed CCL17 and highly expressed HLA-DR following the addition of the mite antigen. Taken together, these data show that monocyte-derived iPS cells can be used to differentiate into monocytes and DCs. In addition, the use of these cells can be applied to the pathological analysis of dendritic cell therapy and monocyte diseases.
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Diferenciação Celular , Células Dendríticas/fisiologia , Células-Tronco Pluripotentes Induzidas/fisiologia , Monócitos/fisiologia , Receptor 1 de Quimiocina CX3C/análise , Receptor 1 de Quimiocina CX3C/metabolismo , Células Cultivadas , Quimiocina CCL17/análise , Quimiocina CCL17/metabolismo , Células Dendríticas/transplante , Feminino , Citometria de Fluxo , Antígenos HLA-DR/análise , Antígenos HLA-DR/metabolismo , Voluntários Saudáveis , Humanos , Imunoterapia/métodos , Receptores de Lipopolissacarídeos/análise , Receptores de Lipopolissacarídeos/metabolismo , Masculino , Pessoa de Meia-Idade , Cultura Primária de Células/métodosRESUMO
BACKGROUND: Myeloperoxidase anti-neutrophil cytoplasmic antibody-related nephritis (MPO-ANCA nephritis) is occasionally accompanied by lung abnormalities such as pulmonary fibrosis. However, the clinical features of pulmonary fibrosis in patients with MPO-ANCA nephritis have not been well documented. This study was performed to compare the prognosis of a usual interstitial pneumonia (UIP) pattern of lung fibrosis in patients with MPO-ANCA nephritis with the prognosis of idiopathic pulmonary fibrosis (IPF). METHODS: We retrospectively reviewed the medical records of 126 patients with MPO-ANCA nephritis and identified 31 with a UIP pattern of lung fibrosis on high-resolution or thin-slice computed tomography (CT). We compared the characteristics and prognosis of these patients with those of 32 patients with IPF. In 18 patients from both groups, we assessed and compared the decline in lung volume over time using three-dimensional (3D) CT images reconstructed from thin-section CT data. RESULTS: The numbers of male and female patients were nearly equal among patients with MPO-ANCA nephritis exhibiting a UIP pattern; in contrast, significant male dominancy was observed among patients with IPF (p = 0.0021). Significantly fewer smokers were present among the patients with MPO-ANCA nephritis with a UIP pattern than among those with IPF (p = 0.0062). There was no significant difference in the median survival time between patients with MPO-ANCA nephritis with a UIP pattern (50.8 months) and IPF (55.8 months; p = 0.65). All patients with IPF in this cohort received antifibrotic therapy (pirfenidone or nintedanib). Almost half of the deaths that occurred in patients with MPO-ANCA nephritis with a UIP pattern were caused by non-respiratory-related events, whereas most deaths in patients with IPF were caused by respiratory failure such as acute exacerbation. In the 3D CT lung volume analyses, the rate of decline in lung volume was equivalent in both groups. CONCLUSIONS: MPO-ANCA nephritis with a UIP pattern on CT may have an unfavorable prognosis equivalent to that of IPF with a UIP pattern treated with antifibrotic agents.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Pulmão/patologia , Nefrite/imunologia , Fibrose Pulmonar/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Anticorpos Anticitoplasma de Neutrófilos/sangue , Causas de Morte , Feminino , Humanos , Fibrose Pulmonar Idiopática/mortalidade , Imageamento Tridimensional , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Peroxidase/imunologia , Prognóstico , Fibrose Pulmonar/mortalidade , Insuficiência Respiratória/etiologia , Estudos Retrospectivos , Taxa de Sobrevida , Tomografia Computadorizada por Raios XRESUMO
Lymphocyte profiles in mediastinal lymph nodes may reflect the immune status of patients with sarcoidosis. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is useful for the diagnosis of diseases with mediastinal lymphadenopathy including sarcoidosis. The purpose of this study was to determine lymphocyte profiles of lymph nodes in sarcoidosis by analyzing EBUS-TBNA samples. We prepared single cell suspensions from EBUS-TBNA samples of mediastinal lymph nodes from patients with sarcoidosis or lung cancer and analyzed surface markers (CD3, CD4, CD8, CD19, CD25) and FoxP3 expression in the resultant lymphocytes using flow cytometry. We studied 26 patients with sarcoidosis and 16 with lung cancer with mediastinal lymph node metastases. In sarcoidosis, the CD4/CD8 ratio was significantly more elevated in lymph nodes than in bronchoalveolar lavage fluid (P<0.001), although both were strongly correlated. The CD4/CD8 ratio was significantly higher in stage I than in stage II both in the BAL fluid and lymph nodes. When compared with lung cancer lymph node metastasis, the CD4/CD8 ratio was significantly higher in sarcoidosis, whereas the CD3/CD19 ratio was significantly higher in lung cancer. The proportion of regulatory T cells (CD4+, CD25+, FoxP3 high) did not differ between sarcoidosis and lung cancer samples. Lymphocyte profiles in mediastinal lymphadenopathy can be analyzed by flow cytometry of EBUS-TBNA samples. These findings might help elucidate the immunopathology of sarcoidosis.
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Citometria de Fluxo , Linfadenopatia/metabolismo , Linfócitos/metabolismo , Doenças do Mediastino/metabolismo , Sarcoidose/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Biópsia , Relação CD4-CD8 , Feminino , Citometria de Fluxo/métodos , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Linfadenopatia/diagnóstico , Masculino , Doenças do Mediastino/diagnóstico , Pessoa de Meia-Idade , Sarcoidose/diagnóstico , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Adulto JovemRESUMO
In recent research on regenerative medicine, three-dimensional (3D) tissue reconstruction using the induced pluripotent stem cell (iPS cell) differentiated cells has attracted attention. In this study, mouse lungs at 1.5, 10, and 20 d old were subjected to enzyme treatment, and aggregates formed in serum-free suspension culture (3D-culture) were observed. The number of aggregates formed was the highest in 1.5 d. The cell aggregates in which the interior of the aggregate is filled and form small vacuoles and the organoid-like aggregates having a relatively large vacuole inside and forming the alveolar-like structure were observed. At 1.5 d, the formation ratio of the organoid-like aggregates was the highest and aggregate size was small at 20 d. For the cell aggregates derived from 1.5 d, positive cells of SSEA-1, CD29, CD90, CD105, alveolar epithelial stem cell marker of SP-C, and Sca-1 were observed in the center. In the cell aggregates derived from 10 d, the expression level of 1.5 d each protein markers and OCT4 gene of transcription factor was decreased, and furthermore, markers were hardly observed in the organoid-like aggregates derived from 10 d. In addition, cells surrounding the vacuole of organoid-like aggregate obtained over 10 d differentiated into periodic acid-Schiff (PAS), podoplanin-positive cells. When the formed cell aggregates were dispersed, cell aggregates and organoid-like aggregates were reformed. Comparing 3D-culture and adhesion culture (2D-culture), SP-C expression of 10 d of cells was maintained. Expression of markers of undifferentiated markers and alveolar tissue stem cells decreased when cell aggregates were cultured with the addition of fetal bovine serum.
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Alvéolos Pulmonares/citologia , Mucosa Respiratória/citologia , Células-Tronco/citologia , Animais , Biomarcadores/metabolismo , Adesão Celular , Agregação Celular , Diferenciação Celular , Forma Celular , Células Cultivadas , Regulação da Expressão Gênica , Camundongos Endogâmicos C57BL , Coloração e Rotulagem , Células-Tronco/metabolismoRESUMO
Objective Sleep apnea syndrome is more prevalent among men than women and is frequently accompanied by metabolic syndrome (MetS). However, gender differences in the effect of sleep-disordered breathing (SDB) leading to the risk of MetS remain unclear. The aim of our study was to investigate the clinical characteristics of SDB in women and the differential influence of SDB on MetS between genders. Methods In a single-center retrospective study, we compared the data of 1,809 consecutive SDB patients by gender to clarify the characteristics of sleep disorders in women. We also compared the prevalence of MetS and its related abnormalities by gender. A logistic regression analysis was used to determine the contributory factors for MetS. Results The mean age and proportion of patients over 50 years of age were higher in women than in men. SDB was milder in women than in men according to polysomnography findings. Elevated Hemoglobin A1c levels and hyperlipidemia were less frequent in women than in men. The MetS prevalence was similar in women and men (30.0% vs. 35.2%). A logistic regression analysis showed that the apnea-hypopnea index (AHI) was an independent risk factor for MetS in both genders, but that female gender was independently associated with a decreased prevalence of MetS and its related abnormalities. Conclusion Female SDB patients tend to be older with milder apnea and sleepiness than male SDB patients. A higher AHI is a significant risk factor for MetS in both genders, although female gender is an independent inhibitory factor for developing MetS in SDB patients.
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Síndrome Metabólica/epidemiologia , Síndromes da Apneia do Sono/epidemiologia , Síndromes da Apneia do Sono/fisiopatologia , Fatores Etários , Idoso , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Polissonografia , Prevalência , Estudos Retrospectivos , Fatores de Risco , Fatores SexuaisRESUMO
Since induced pluripotent stem (iPS) cells have been established, in recent years, clinical transplantation of cells differentiated from iPS cells derived from human skin fibroblasts is been in progress. On the contrary, monocytes have complete genome information without damage and gene recombination, they are contained in the peripheral blood by â¼3%-8% and differentiate into dendritic cells that are the type of control tower for immune cells. However, generation of monocyte-derived iPS cells has only been successful when special persistent Sendai virus vectors have been used. Therefore, in this study, as a preculture method for monocytes, a culture method for maintaining activity without using any cytokine was established, and using a commercially available vector without genetic toxicity without damaging the chromosome of the cell, iPS cells derived from monocytes were successfully produced. This cell has the ability to differentiate into three germ layers, and when compared with commercially available iPS cells, there was no significant difference between self-renewal and gene expression in the three germ layers. In future, we will compare the differentiation induction of monocyte-derived iPS cells with dendritic cells and investigate the production of dendritic cells that can cope with various antigens.
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Vetores Genéticos , Células-Tronco Pluripotentes Induzidas , Monócitos , Vírus Sendai , Animais , Técnicas de Cultura de Células , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Camundongos , Monócitos/citologia , Monócitos/metabolismoRESUMO
BACKGROUND: When epidermal growth factor receptor (EGFR) gene mutation-positive non-small cell lung cancer (NSCLC) acquires resistance to the initial tyrosine kinase inhibitor (TKI) treatment, reassessing the tumor DNA by re-biopsy is essential for further treatment selection. However, the process of TKI-sensitive tumor re-progression and whether re-biopsy is possible in all cases of acquired resistance to EGFR-TKI remain unclear. METHODS: We retrospectively analyzed data from 69 consecutive patients with EGFR gene mutation-positive advanced NSCLC who had been treated with EGFR-TKI and exhibited disease relapse after initial disease remission. The relapsing lesions were identified at the time of RECIST-progressive disease (PD) and clinical-PD (when the attending physician judged the patient as clinically relapsing and stopped EGFR-TKI therapy). We determined the potential re-biopsy methods for each relapsing lesion and evaluated their feasibility according to difficulty and invasiveness criteria as follows: category A, accessible by conventional biopsy techniques; category B, difficult (but possible) to biopsy and accessible with invasive methods; and category C, extremely difficult to biopsy or inaccessible without using highly invasive methods, including surgical biopsy. RESULTS: The total feasibility rate of re-biopsy (category A or B) was 68% at RECIST-PD and 84% at clinical-PD, and the most common accessible relapsing lesions were primary tumors at RECIST-PD and pleural effusion at clinical-PD. All relapsing lesions at primary sites (categories A and B) were assessed as having the potential for re-biopsy. However, re-biopsy for metastasis was assessed as difficult in a substantial proportion of the study population (42 and 20% category C at RECIST-PD and clinical-PD, respectively). CONCLUSIONS: Re-biopsy of relapsing disease is feasible in many cases, although it may present difficulties in cases with, e.g., metastatic relapsing lesions. To facilitate treatment strategies in NSCLC patients with relapse after EGFR-TKI therapy, re-biopsy should be standardized with the use of simpler and more reliable methods.
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Adenocarcinoma/genética , Biópsia/métodos , Carcinoma Pulmonar de Células não Pequenas/genética , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Recidiva Local de Neoplasia/genética , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha , Broncoscopia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Coortes , Progressão da Doença , Receptores ErbB/antagonistas & inibidores , Estudos de Viabilidade , Feminino , Humanos , Biópsia Guiada por Imagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: The purpose of this study was to evaluate renal function in lung cancer patients who were administered cisplatin with continuous higher-volume hydration (CH) or a short hydration (SH) regimen. METHODS: We retrospectively evaluated patients with lung cancer who were treated with chemotherapy regimens including >50 mg/m2 of cisplatin between August 2007 and March 2015. Between August 2007 and December 2012, patients received a continuous higher-volume hydration regimen without magnesium (Mg) supplementation (CH group), and after May 2013, patients received a short hydration regimen with Mg supplementation (SH group). To evaluate the factors influencing serum creatinine (SCr) increase during the first course of cisplatin chemotherapy, univariate and multivariate logistic regression analyses were conducted. RESULTS: A total of 122 patients were evaluated, 62 patients in the CH group and 60 patients in the SH group. Grade 1 (National Cancer Institute Common Toxicity Criteria for Adverse Events; version 4.0) or higher SCr increases were more frequently observed in the CH group than in the SH group after the first cycle (P = 0.01, Fisher's exact test) and for all cycles (P = 0.03). Multivariate analysis revealed that short hydration (odds ratio (OR), 0.30; 95% confidence internal (CI) (0.11-0.75), P = 0.01) and estimated creatinine clearance (eCcr) of ≥70 mL/min (OR, 0.25; 95% CI (0.088-0.69), P = 0.008) were associated with a significantly reduced risk for cisplatin-induced grade 1 or higher SCr increase. CONCLUSION: Our study suggested that a short hydration method with Mg supplementation and eCcr of ≥70 mL/min reduced the risk of cisplatin-induced nephrotoxicity.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/toxicidade , Rim/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Magnésio/uso terapêutico , Adulto , Idoso , Feminino , Humanos , Rim/metabolismo , Rim/patologia , Neoplasias Pulmonares/complicações , Magnésio/administração & dosagem , Magnésio/farmacologia , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosAssuntos
Monofosfato de Adenosina/administração & dosagem , Asma Induzida por Aspirina/fisiopatologia , Hiper-Reatividade Brônquica/fisiopatologia , Testes de Provocação Brônquica , Hipersensibilidade Respiratória/fisiopatologia , Adulto , Feminino , Humanos , Masculino , Cloreto de Metacolina/administração & dosagem , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Bronchial occlusion with an Endobronchial Watanabe Spigot (EWS) has been shown to be useful in managing prolonged bronchopleural fistulas and intractable hemoptysis. EWS bronchial occlusion using a curette is less technically demanding. This retrospective study evaluated the clinical utility and simplicity of this method. METHODS: A total of 18 consecutive patients (15 men, 3 women, aged 47-85 years) who underwent bronchial occlusion using an EWS from April 2012 to August 2014 were evaluated. The method involves sticking the tip of a curette into an EWS to the first joint, allowing it to be turned in any direction or at any angle. The time required to occlude the target bronchus was measured on routinely recorded digital videos. Other parameters evaluated included success rates, complications, and clinical outcomes. RESULTS: Of the 18 patients, 11 underwent bronchial occlusion for intractable pneumothorax, 5 for postoperative bronchopleural fistula, two for intractable empyema, and one for hemoptysis. Each patient required 1-7 EWSs (median 4). Target bronchi included the right upper (n = 8), left upper (n = 5), right lower (n = 2), left lower (n = 2), and right middle (n = 1) bronchi. The success rate of EWS insertion into the target bronchus was 100%. Time per EWS occlusion ranged from 65-528 sec (median 158.5 sec). Of the 62 insertions, 36 (58.1%) were completed within 3 min, and 58 (93.5%) within 5 min. Successful outcomes were observed in 15 (83.3%) of the 18 patients. CONCLUSIONS: EWS bronchial occlusion using a curette is a simple method for managing intractable bronchopleural fistulas in daily clinical settings.
Assuntos
Fístula Brônquica/terapia , Doenças Pleurais/terapia , Pneumotórax/terapia , Oclusão Terapêutica/métodos , Idoso , Idoso de 80 Anos ou mais , Empiema/terapia , Feminino , Hemoptise/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Elastômeros de Silicone , Oclusão Terapêutica/instrumentação , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Recent advances in bronchoscopy, such as transbronchial biopsy (TBB) using endobronchial ultrasonography with a guide sheath (EBUS-GS), have improved the diagnostic yield of small-sized peripheral lung lesions. In some cases, however, it is difficult to obtain adequate biopsy samples for pathological diagnosis. Adequate prediction of the diagnostic accuracy of TBB with EBUS-GS is important before deciding whether bronchoscopy should be performed. METHODS: We retrospectively reviewed 149 consecutive patients who underwent TBB with EBUS-GS for small-sized peripheral lung lesions (≤30 mm in diameter) from April 2012 to March 2013. We conducted an exploratory analysis to identify clinical factors that can predict an accurate diagnosis by TBB with EBUS-GS. All patients underwent thin-section chest computed tomography (CT) scans (0.5-mm slices), and the CT bronchus sign was evaluated before bronchoscopy in a group discussion. The final diagnoses were pathologically or clinically confirmed in all studied patients (malignant lesions, 110 patients; benign lesions, 39 patients). RESULTS: The total diagnostic yield in this study was 72.5% (95% confidence interval: 64.8-79.0%). Lesion size, lesion visibility on chest X-ray, and classification of the CT bronchus sign were factors significantly associated with the definitive biopsy result in the univariate analysis. In the multivariate analysis, only the CT bronchus sign remained as a significant predictive factor for successful bronchoscopic diagnosis. The CT bronchus sign was also significantly associated with the EBUS findings of the lesions. CONCLUSION: Our results suggest that the CT bronchus sign is a powerful predictive factor for successful TBB with EBUS-GS.