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1.
Oncology ; 102(1): 67-75, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37527640

RESUMO

INTRODUCTION: Altered lipid metabolism has been reported to be associated with prognosis in multiple cancers. This study aimed to investigate the association of polymorphisms in lipid metabolism pathway genes with survival outcomes in patients with surgically resected non-small cell lung cancer (NSCLC). METHODS: In total, 744 patients with surgically resected NSCLC (380 in the discovery cohort and 364 in the validation cohort) were included in this study. The association between 176 polymorphisms of lipid metabolism pathway genes and the clinical outcomes of NSCLC patients was analyzed. RESULTS: Among the polymorphisms investigated, ACADSB rs10902859G>A was associated with significantly better overall survival (OS) in the discovery, validation, and combined cohorts. ACADSB rs10902859G>A was located in the repressed region and had strong linkage disequilibrium (D' = 1.00 and r2 = 0.94), with rs12220683G>C located in the H3K4me3 peak region, which indicates the presence of active promoters. ACADSB rs12220683G>C was also associated with better OS in the discovery, validation, and combined cohorts (in a dominant model; adjusted hazard ratio [aHR] = 0.53, 95% confidence interval [CI] = 0.30-0.94, p = 0.03; aHR = 0.37, 95% CI = 0.15-0.89, p = 0.03; and aHR = 0.47, 95% CI = 0.29-0.75, p = 0.002, respectively). In vitro luciferase assay demonstrated that the promoter activity of ACADSB was significantly increased in the rs12220683 variant C allele compared with that in the wild G allele (p = 3 × 10-5). CONCLUSION: These results suggest that ACADSB rs12220683G>C increases promoter activity and that increased ACADSB expression may result in better OS in patients with surgically resected NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/genética , Metabolismo dos Lipídeos/genética , Genótipo , Polimorfismo de Nucleotídeo Único , Prognóstico
2.
Respiration ; 103(5): 257-267, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38499001

RESUMO

INTRODUCTION: Data on factors related to mortality in patients with bronchiectasis exacerbation are insufficient. Computed tomography (CT) can measure the pectoralis muscle area (PMA) and is a useful tool to diagnose sarcopenia. This study aimed to evaluate whether PMA can predict mortality in patients with bronchiectasis exacerbation. METHODS: Patients hospitalized due to bronchiectasis exacerbation at a single center were retrospectively divided into survivors and non-survivors based on 1-year mortality. Thereafter, a comparison of the clinical and radiologic characteristics was conducted between the two groups. RESULTS: A total of 66 (14%) patients died at 1 year. In the multivariate analysis, age, BMI <18.4 kg/m2, sex-specific PMA quartile, ≥3 exacerbations in the previous year, serum albumin <3.5 g/dL, cystic bronchiectasis, tuberculosis-destroyed lung, and diabetes mellitus were independent predictors for the 1-year mortality in patients hospitalized with bronchiectasis exacerbation. A lower PMA was associated with a lower overall survival rate in the survival analysis according to sex-specific quartiles of PMA. PMA had the highest area under the curve during assessment of prognostic performance in predicting the 1-year mortality. The lowest sex-specific PMA quartile group exhibited higher disease severity than the highest quartile group. CONCLUSIONS: CT-derived PMA was an independent predictor of 1-year mortality in patients hospitalized with bronchiectasis exacerbation. Patients with lower PMA exhibited higher disease severity. These findings suggest that PMA might be a useful marker for providing additional information regarding prognosis of patients with bronchiectasis exacerbation.


Assuntos
Bronquiectasia , Progressão da Doença , Músculos Peitorais , Tomografia Computadorizada por Raios X , Humanos , Masculino , Feminino , Bronquiectasia/mortalidade , Bronquiectasia/diagnóstico por imagem , Idoso , Músculos Peitorais/diagnóstico por imagem , Estudos Retrospectivos , Pessoa de Meia-Idade , Hospitalização , Sarcopenia/diagnóstico por imagem , Sarcopenia/mortalidade , Sarcopenia/diagnóstico , Prognóstico
3.
Oncology ; 101(2): 96-104, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36257285

RESUMO

OBJECTIVE: This study was conducted to investigate the association between genetic variants in histone modification regions and clinical outcomes of PEM chemotherapy in patients with lung adenocarcinoma. METHODS: Potentially functional SNPs were selected using integrated analysis of ChIP-seq and RNA-seq. The associations of 279 SNPs with chemotherapy response and overall survival (OS) were analyzed in 314 lung adenocarcinoma patients who underwent PEM chemotherapy. RESULTS: Among the SNPs investigated, 18 were significantly associated with response to chemotherapy, while 28 with OS. Of these SNPs, rs549794A>G in an enhancer which is expected to regulate the expression of ribosomal protein S3 (RPS3) gene was significantly associated with both worse response to chemotherapy and worse OS (adjusted odds ratio = 0.59, 95% CI = 0.36-0.97, p = 0.04; adjusted hazard ratio = 1.44, 95% CI = 1.09-1.91, p = 0.01, respectively). Previous studies suggested that RPS3, a multi-functional protein with various extraribosomal activities, may play a role in chemotherapy resistance. Therefore, it is postulated that rs549794-induced change in the expression level of RPS3 may affect the response to PEM chemotherapy and consequently the survival outcomes in lung adenocarcinoma patients. CONCLUSION: This study suggests that genetic variants in the histone modification regions may be useful for the prediction of clinical outcomes of PEM chemotherapy in advanced lung adenocarcinoma.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Pemetrexede/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Código das Histonas , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
4.
J Korean Med Sci ; 38(45): e381, 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-37987107

RESUMO

BACKGROUND: Neurogenic differentiation 1 (NeuroD1) is a representative small cell lung cancer (SCLC) transcription regulator involved in the carcinogenesis and behavior of SCLC. Histone modifications play an important role in transcription, and H3 lysine 4 trimethylation (H3K4me3) is primarily associated with promoter regions. METHODS: We investigated the association between single nucleotide polymorphisms (SNPs) in NeuroD1 and H3K4me3 coincident regions, selected using ChIP sequencing (ChIP-seq), and the clinical outcomes of 261 patients with SCLC. RESULTS: Among 230 SNPs, two were significantly associated with both the chemotherapy response and overall survival (OS) of patients with SCLC. RNF145 rs2043268A>G was associated with worse chemotherapy response and OS (under a recessive model, adjusted odds ratio [aOR], 0.50, 95% confidence interval [CI], 0.26-0.94, P = 0.031, and adjusted hazard ratio [aHR], 1.88, 95% CI, 1.38-2.57, P < 0.001). CINP rs762105A>G was also associated with worse chemotherapy response and OS (under a dominant model, aOR, 0.47, 95% CI, 0.23-0.99, P = 0.046, and aHR, 2.03, 95% CI, 1.47-2.82, P < 0.001). ChIP-quantitative polymerase chain reaction and luciferase assay confirmed that the two SNPs were located in the active promoter regions and influenced the promoter activity of each gene. CONCLUSION: To summarize, among SNPs selected using ChIP-seq in promoter regions with high peaks in both NeuroD1 and H3K4me3, RNF145 rs2043268A>G and CINP rs762105A>G were associated with clinical outcomes in patients with SCLC and also affected the promoter activity of each gene.


Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Histonas/genética , Histonas/metabolismo , Histonas/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Regiões Promotoras Genéticas , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/genética
5.
J Infect Chemother ; 28(1): 47-53, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34627705

RESUMO

INTRODUCTION: Patients with aspiration pneumonia (AP) exhibit higher mortality than those with non-AP. However, data regarding predictors of short-term prognosis in patients with community-acquired AP are limited. METHODS: Patients hospitalized with community-acquired pneumonia (CAP) were retrospectively classified into aspiration pneumonia (AP) and non-AP groups. The AP patients were further divided into nonsurvivors and survivors by 30-day mortality, and various clinical variables were compared between the groups. RESULTS: Of 1249 CAP patients, 254 (20.3%) were classified into the AP group, of whom 76 patients (29.9%) died within 30 days. CURB-65, pneumonia severity index (PSI), and Infectious Diseases Society of America/American Thoracic Society criteria for severe CAP (SCAP) showed only modest prognostic performance for the prediction of 30-day mortality (c-statistics, 0.635, 0.647, and 0.681, respectively). Along with the PSI and SCAP, Eastern Cooperative Oncology Group performance status (ECOG-PS) and blood biomarkers, including, N-terminal of prohormone brain natriuretic peptide (NT-proBNP) and albumin, were independent predictors of 30-day mortality. In models based on clinical prediction rules, including CURB-65, PSI, and SCAP, the addition of ECOG-PS further improved their c-statistics compared to the clinical prediction rules alone. In the four combinations based on SCAP, ECOG-PS, and two blood biomarkers (NT-proBNP and albumin), the c-statistics further increased to reach approximately 0.8. CONCLUSIONS: CURB-65, PSI, and SCAP exhibited only modest discriminatory power in predicting the 30-day mortality of patients with community-acquired AP. The addition of performance status and blood biomarkers, including NT-proBNP and albumin, further increased prognostic performance, showing good predictive accuracy in the SCAP-based model.


Assuntos
Infecções Comunitárias Adquiridas , Pneumonia Aspirativa , Pneumonia , Humanos , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença
6.
Oncology ; 99(5): 336-344, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33626541

RESUMO

BACKGROUND: Activating transcription factor 3 (ATF3) plays a significant role in cancer development and progression. We investigated the association between variants in expression quantitative trait loci (eQTLs) within ATF3 binding regions and the prognosis of non-small cell lung cancer (NSCLC) after surgery. METHODS: A total of 772 patients with NSCLC who underwent curative surgery were enrolled. Using a public database (http://galaxyproject.org), we selected 104 single nucleotide polymorphisms (SNPs) in eQTLs in the ATF3 binding regions. The association of those SNPs with disease-free survival (DFS) was evaluated. RESULTS: Among those SNPs, HAX1 rs11265425T>G was associated with significantly worse DFS (aHR = 1.30, 95% CI = 1.00-1.69, p = 0.05), and ME3 rs10400291C>A was associated with significantly better DFS (aHR = 0.66, 95% CI = 0.46-0.95, p = 0.03). Regarding HAX1 rs11265425T>G, the significant association remained only in adenocarcinoma, and the association was significant only in squamous cell carcinoma regarding ME3 rs10400291C>A. ChIP-qPCR assays showed that the two variants reside in active enhancers where H3K27Ac and ATF3 binding occurs. Promoter assays showed that rs11265425 G allele had significantly higher HAX1 promoter activity than T allele. HAX1 RNA expression was significantly higher in tumor than in normal lung, and higher in rs11265425 TG+GG genotypes than in TT genotype. Conversely, ME3 expression was significantly lower in tumor than in normal lung, and higher in rs10400291 AA genotype than in CC+CA genotypes. CONCLUSIONS: In conclusion, this study shows that the functional polymorphisms in ATF3 binding sites, HAX1 rs11265425T>G and ME3 rs10400291C>A are associated with the clinical outcomes of patients in surgically resected NSCLC.


Assuntos
Fator 3 Ativador da Transcrição/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Álcool Oxidorredutases Dependentes de NAD(+) e NADP(+)/metabolismo , Polimorfismo de Nucleotídeo Único , Fator 3 Ativador da Transcrição/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/cirurgia , Sítios de Ligação , Biomarcadores Tumorais/genética , Carcinoma de Células Grandes/genética , Carcinoma de Células Grandes/metabolismo , Carcinoma de Células Grandes/patologia , Carcinoma de Células Grandes/cirurgia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Feminino , Seguimentos , Genótipo , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Álcool Oxidorredutases Dependentes de NAD(+) e NADP(+)/genética , Prognóstico , Regiões Promotoras Genéticas , Taxa de Sobrevida
7.
J Korean Med Sci ; 36(1): e10, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33398944

RESUMO

The cause of epithelioid granulomatous inflammation varies widely depending on the affected organ, geographic region, and whether the granulomas morphologically contain necrosis. Compared with other organs, the etiological distribution and morphological patterns of pleural epithelioid granulomas have rarely been investigated. We evaluated the final etiologies and morphological patterns of pleural epithelioid granulomatous inflammation in a tuberculosis (TB)-prevalent country. Of 83 patients with pleural granulomas, 50 (60.2%) had confirmed TB pleurisy (TB-P) and 29 (34.9%) had probable TB-P. Four patients (4.8%) with non-TB-P were diagnosed. With the exception of microbiological results, there was no significant difference in clinical characteristics and granuloma patterns between the confirmed TB-P and non-TB-P groups, or between patients with confirmed and probable TB-Ps. These findings suggest that most pleural granulomatous inflammation (95.2%) was attributable to TB-P in TB-endemic areas and that the granuloma patterns contributed little to the prediction of final diagnosis compared with other organs.


Assuntos
Granuloma/patologia , Pleurisia/diagnóstico , Tuberculose/diagnóstico , Adenosina Desaminase/metabolismo , Adulto , Algoritmos , DNA Bacteriano/metabolismo , Feminino , Granuloma/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Pleura/metabolismo , Pleurisia/complicações , Tuberculose/complicações , Tuberculose/microbiologia
8.
Oncology ; 98(7): 468-477, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32252059

RESUMO

OBJECTIVE: This study was conducted to investigate whether polymorphisms in glycolysis-related genes are associated with clinical outcomes of patients with advanced-stage non-small cell lung cancer (NSCLC) undergoing chemotherapy. METHODS: A total of 377 patients with NSCLC were enrolled. Sixty-five single-nucleotide polymorphisms in 26 genes involved in the glycolytic pathway were evaluated. The associations of the variants with the chemotherapy response and overall survival (OS) were analyzed. RESULTS: Among the 65 variants investigated, PFKL rs2073436C>G and GPI rs7248411C>G significantly correlated with clinical outcomes after chemotherapy in multivariate analyses. PFKL rs2073436C>G was significantly associated with both a worse response to chemotherapy (adjusted odds ratio [aOR] = 0.64, 95% CI = 0.45-0.90, p = 0.01) and a worse OS (adjusted hazard ratio [aHR] = 1.35, 95% CI = 1.14-1.61, p = 0.001). GPI rs7248411C>G was significantly associated with both a better chemotherapy response (aOR = 1.58, 95% CI = 1.07-2.23, p = 0.02) and a better OS (aHR = 0.80, 95% CI = 0.66-0.98, p = 0.03). When stratified by tumor histology, PFKL rs2073436C>G was significantly associated with OS only in squamous cell carcinoma, whereas GPI rs7248411C>G exhibited a significant association with the chemotherapy response and OS only in adenocarcinoma. CONCLUSION: This result suggests that the PFKL rs2073436C>G and GPI rs7248411C>G are useful for predicting the clinical outcome of first-line paclitaxel-cisplatin chemotherapy in NSCLC.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Glicólise/genética , Neoplasias Pulmonares/tratamento farmacológico , Polimorfismo de Nucleotídeo Único , Adenocarcinoma/mortalidade , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma de Células Escamosas/mortalidade , Cisplatino/uso terapêutico , Citocinas/genética , Feminino , Glucose-6-Fosfato Isomerase/genética , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Paclitaxel/uso terapêutico , Fosfofrutoquinase-1 Hepática/genética , Prognóstico , Taxa de Sobrevida , Resultado do Tratamento
9.
Oncology ; 98(12): 897-904, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32791502

RESUMO

BACKGROUND: This study was conducted to investigate the association between genetic variants in one-carbon metabolism and survival outcomes of surgically resected non-small cell lung cancer (NSCLC). METHODS: We genotyped 41 potentially functional variants of 19 key genes in the one-carbon metabolism pathway among 750 NSCLC patients who underwent curative surgery. The association between genetic variants and overall survival (OS)/disease-free survival (DFS) were analyzed. RESULTS: Among the 41 single-nucleotide polymorphisms (SNPs) analyzed, 4 SNPs (MTHFD1L rs6919680T>G and rs3849794T>C, MTR rs2853523C>A, and MTHFR rs4846049G>T) were significantly associated with survival outcomes. MTHFD1L rs6919680T>G and MTR rs2853523C>A were significantly associated with better OS (adjusted hazard ratio [aHR] = 0.73, 95% confidence interval [CI] = 0.54-0.99, p = 0.04) and worse OS (aHR = 2.14, 95% CI = 1.13-4.07, p = 0.02), respectively. MTHFD1L rs3849794T>C and MTHFR rs4846049G>T were significantly associated with worse DFS (aHR = 1.41, 95% CI = 1.08-1.83, p = 0.01; and aHR = 1.97, 95% CI = 1.10-3.53, p = 0.02, respectively). When the patients were divided according to histology, the associations were significant only in squamous cell carcinoma (SCC), but not in adenocarcinoma (AC). In SCC, MTHFD1L rs6919680T>G and MTR rs2853523C>A were significantly associated with better OS (aHR = 0.64, 95% CI = 0.41-1.00, p = 0.05) and worse OS (aHR = 2.77, 95% CI = 1.11-6.91, p = 0.03), respectively, and MTHFD1L rs3849794T>C and MTHFR rs4846049G>T were significantly associated with worse DFS (aHR = 1.73, 95% CI = 1.17-2.56, p = 0.01; and aHR = 2.78, 95% CI = 1.12-6.88, p = 0.03, respectively). CONCLUSIONS: Our results suggest that the genetic variants in the one-carbon metabolism pathway could be used as biomarkers for predicting the clinical outcomes of patients with early-stage NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Proteínas de Neoplasias/genética , Transferases de Grupo de Um Carbono/genética , Prognóstico , Idoso , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Intervalo Livre de Doença , Feminino , Variação Genética/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade
10.
Ann Surg Oncol ; 26(11): 3756-3764, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31313037

RESUMO

BACKGROUND: We evaluated the association between genetic variants in the Notch pathway and survival outcomes of patients with surgically resected NSCLC. METHODS: Sixty-four single nucleotide polymorphisms (SNPs) in the Notch pathway genes were evaluated in the discovery study (n = 354) and two sequential validation studies (n = 772 and n = 746, respectively). The association of genotype with overall survival (OS) and disease-free survival (DFS) was evaluated. RESULTS: Of the 64 SNPs analyzed in the discovery study, 9 were significantly associated with OS or DFS. Among them, the association remained significant only for Deltex-1 (DTX1) rs1732786A>G in the first validation study. The second validation study confirmed again the association between DTX1 rs1732786A>G and survival outcomes. In the combined analysis, rs1732786A>G was significantly associated with better OS and DFS (adjusted HR ·aHR· for OS, 0.75; 95% CI 0.64-0.87; P = 0.0002; aHR for DFS, 0.79; 95% CI 0.71-0.89; P = 0.0001). In vitro luciferase assay showed that the rs1732786G allele was associated with higher promoter activity compared to rs1732786A allele. Consistently, relative mRNA expression level of DTX1 showed significant positive correlation with rs1732786 A-to-G change (Ptrend = 0.02) in tumor tissues. CONCLUSIONS: These results suggest that DTX1 rs1732786 is a potential prognostic factor that may have clinical utility in the management of early stage NSCLC.


Assuntos
Adenocarcinoma/mortalidade , Carcinoma de Células Grandes/mortalidade , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma de Células Escamosas/mortalidade , Neoplasias Pulmonares/mortalidade , Polimorfismo de Nucleotídeo Único , Ubiquitina-Proteína Ligases/genética , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Biomarcadores Tumorais/genética , Carcinoma de Células Grandes/genética , Carcinoma de Células Grandes/patologia , Carcinoma de Células Grandes/cirurgia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Feminino , Seguimentos , Genótipo , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Prognóstico , Taxa de Sobrevida
11.
Respiration ; 97(6): 508-517, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30625485

RESUMO

BACKGROUND: Data regarding community-acquired pneumonia (CAP) identified on chest computed tomography (CT) but not on chest radiography (CR) are limited. OBJECTIVES: The present study aimed to investigate the clinical and radiological features of these patients. METHODS: We retrospectively compared the clinical characteristics, etiological agents, treatment outcomes, and CT findings between CAP patients with negative CR and positive CT findings (negative CR group) and those with positive CR as well as CT findings (control group). RESULTS: Of 1,925 patients, 94 patients (4.9%) were included in the negative CR group. Negative CR findings could be attributed to the location of the lesions (e.g., those located in the dependent lung) and CT pattern with a low attenuation, such as ground-glass opacity (GGO). The negative CR group was characterized by a higher frequency of aspiration pneumonia, lower incidences of complicated parapneumonic effusion or empyema and pleural drainage, and lower blood levels of inflammatory markers than the control group. On CT, the negative CR group exhibited higher rates of GGO- and bronchiolitis-predominant patterns and a lower rate of consolidation pattern. Despite shorter length of hospital stay in the negative CR group, 30-day and in-hospital mortalities were similar between the two groups. CONCLUSIONS: CAP patients with negative CR findings are characterized by lower blood levels of inflammatory markers, a higher incidence of aspiration pneumonia, and a lower incidence of complicated para-pneumonic effusion or empyema than those with positive CR findings. Chest CT scan should be considered in suspected CAP patients with a negative CR, especially in bedridden patients.


Assuntos
Infecções Comunitárias Adquiridas/diagnóstico por imagem , Infecções Comunitárias Adquiridas/microbiologia , Pneumonia/diagnóstico por imagem , Pneumonia/microbiologia , Idoso , Antibacterianos/uso terapêutico , Infecções Comunitárias Adquiridas/terapia , Reações Falso-Negativas , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia/terapia , Radiografia Torácica , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
12.
Cancer Sci ; 109(12): 3902-3909, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30281872

RESUMO

RegulomeDB is a new tool that can predict the regulatory function of genetic variants. We applied RegulomeDB in selecting putative functional variants and evaluated the relationship between these variants and survival outcomes of surgically resected non-small-cell lung cancer. Among the 244 variants studied, 14 were associated with overall survival (P < 0.05) in the discovery cohort and one variant (rs2257609 C>T) was replicated in the validation cohort. In the combined analysis, rs2257609 C>T was significantly associated with worse overall and disease-free survival under a dominant model (P = 2 × 10-5 and P = 0.001, respectively). rs2257609 is located in the SLC5A10 intron, but RegulomeDB predicted that this variant affected DRG2, not SLC5A10 expression. The expression level of SLC5A10 was not different with the rs2257609 genotype. However, DRG2 expression was different according to the rs2257609 genotype (Ptrend   = 0.03) and was significantly higher in tumor than in non-malignant lung tissues (P = 1 × 10-5 ). Luciferase assay also showed higher promoter activity of DRG2 in samples with the rs2257609 T allele (P < 0.0001). rs2257609 C>T affected DRG2 expression and, thus, influenced the prognosis of early-stage non-small-cell lung cancer. This study was approved by the Institutional Review Broad of Kyungpook National University of Hospital (Approval No. KNUMC 2014-04-210-003).


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Proteínas de Ligação ao GTP/genética , Perfilação da Expressão Gênica/métodos , Neoplasias Pulmonares/patologia , Polimorfismo de Nucleotídeo Único , Proteínas de Transporte de Sódio-Glucose/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Estudos de Associação Genética , Variação Genética , Humanos , Íntrons , Neoplasias Pulmonares/genética , Masculino , Estadiamento de Neoplasias , Prognóstico , Regiões Promotoras Genéticas , Análise de Sobrevida
13.
Ann Surg Oncol ; 25(11): 3396-3403, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30062472

RESUMO

BACKGROUND: This study was conducted to investigate whether polymorphisms of glucose transporter 1 (GLUT1) gene are associated with the prognosis of patients with non-small cell lung cancer (NSCLC) after surgical resection. METHODS: Five single nucleotide polymorphisms (SNPs) in GLUT1 were investigated in a total of 354 patients with NSCLC who underwent curative surgery. The association of the SNPs with patients' survival was analyzed. RESULTS: Among the five SNPs investigated, two SNPs (GLUT1 rs3820589T > A and rs4658G > C) were significantly associated with OS in multivariate analyses. GLUT1 rs3820589T > A was associated with significantly better OS (adjusted hazard ratio [aHR] = 0.57, 95% confidence interval [CI] = 0.34-0.94, P = 0.03, under dominant model), and rs4658G > C was associated with significantly worse OS (aHR = 1.91, 95% CI = 1.09-3.33, P = 0.02, under recessive model). In the stratified analysis by tumor histology, the effect of these SNPs on OS was only significant in squamous cell carcinoma but not in adenocarcinoma. When the two SNPs were combined, OS decreased as the number of bad genotypes increased (Ptrend = 4 × 10-3). CONCLUSIONS: This study suggests that genetic variation in GLUT1 may be useful in predicting survival of patients with early stage NSCLC.


Assuntos
Adenocarcinoma/patologia , Carcinoma de Células Grandes/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/patologia , Transportador de Glucose Tipo 1/genética , Neoplasias Pulmonares/patologia , Polimorfismo de Nucleotídeo Único , Adenocarcinoma/genética , Adenocarcinoma/terapia , Biomarcadores Tumorais/genética , Carcinoma de Células Grandes/genética , Carcinoma de Células Grandes/terapia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/terapia , Terapia Combinada , Feminino , Seguimentos , Genótipo , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Taxa de Sobrevida
15.
Ann Surg Oncol ; 24(11): 3386-3395, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28766235

RESUMO

BACKGROUND: This study was conducted to determine whether single-nucleotide polymorphisms (SNPs) in EMT-related genes may influence the prognosis of NSCLC after surgery. METHODS: There were 88 SNPs in EMT-related genes evaluated in a discovery set of 376 patients who underwent curative surgery for NSCLC. Significantly, 14 SNPs were evaluated in a validation set of 428 patients. Luciferase assay and RT-PCR were conducted to examine functional relevance of polymorphisms. RESULTS: Fourteen SNPs that were associated with survival outcomes in a discovery set were selected for validation. Among those, two SNPs (FOXF2 rs1711972A>C and HEYL rs784621G>A) were replicated in a validation study. In combined analysis, FOXF2 rs1711972 AC+CC genotype was associated with significantly better overall survival (OS) and disease-free survival (DFS) compared with AA genotype (adjusted hazard ratio [aHR] for OS = 0.67, 95% confidence interval [CI] 0.51-0.88, P = 0.004; and aHR for DFS = 0.77, 95% CI 0.62-0.95, P = 0.01). HEYL rs784621 AA genotype exhibited a significantly worse OS compared with GG+GA genotype (aHR for OS = 2.65, 95% CI 1.63-4.31, P = 8 × 10-5). FOXF2 rs1711972C allele had a significantly increased promoter activity than rs1711972A allele (P = 0.01), and HEYL rs784621A allele had a significantly lower promoter activity than rs784621G allele (P = 0.004). FOXF2 rs1711972A>C was significantly associated with increased FOXF2 mRNA expression. CONCLUSIONS: FOXF2 rs1711972A>C and HEYL rs784621G>A were associated with survival outcomes of surgically treated NSCLC. These SNPs may help to identify patients at high risk of poor disease outcomes.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Transição Epitelial-Mesenquimal , Fatores de Transcrição Forkhead/genética , Neoplasias Pulmonares/patologia , Polimorfismo de Nucleotídeo Único , Proteínas Repressoras/genética , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Carcinoma de Células Grandes/genética , Carcinoma de Células Grandes/patologia , Carcinoma de Células Grandes/cirurgia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Feminino , Seguimentos , Genótipo , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida
16.
Infection ; 45(1): 59-65, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27488820

RESUMO

PURPOSE: Tuberculous pleural effusion (TPE) and parapneumonic effusion (PPE) are usually distinguished by cellular predominance and pleural fluid adenosine deaminase (ADA) levels. However, both diseases may occasionally show similar neutrophilic predominance and high ADA levels. In such cases, the differential diagnosis between TPE and PPE is challenging and has been rarely investigated. METHODS: A retrospective study was conducted on TPE and PPE patients with neutrophilic exudate and pleural fluid ADA levels ≥40 U/L. Individual and combined parameters of routine blood and pleural fluid tests were compared between the two groups, and receiver operating characteristic (ROC) curves were constructed for identifying TPE. RESULTS: Thirty-six TPE and 41 PPE patients were included. White blood cell counts, serum C-reactive protein (S-CRP), and pleural fluid pH, lactate dehydrogenase, and ADA levels showed significant difference between the two groups (p < 0.001). Among multiple parameters, pleural fluid ADA/S-CRP ratio, which best reflected different local and systemic characteristics between TPE and PPE, provided the highest diagnostic accuracy with an area under the ROC curve of 0.93. At a cutoff value of 5.62, ADA/S-CRP ratio had a sensitivity of 89 %, specificity of 88 %, positive likelihood ratio of 7.29, and negative likelihood ratio of 0.13 for identifying TPE. Additionally, more than half of TPE patients had a ratio above 15.82, while none of PPE patients showed such findings. CONCLUSIONS: Pleural fluid ADA/S-CRP ratio, as a simple method using routine laboratory tests, may be helpful in discriminating between TPE and PPE patients with neutrophilic predominance and ADA ≥40 U/L.


Assuntos
Adenosina Desaminase/análise , Proteína C-Reativa/análise , Derrame Pleural/metabolismo , Tuberculose Pulmonar/diagnóstico , Adulto , Idoso , Exsudatos e Transudatos/química , Exsudatos e Transudatos/citologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neutrófilos , Curva ROC , Estudos Retrospectivos
18.
Respirology ; 22(3): 551-558, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27862706

RESUMO

BACKGROUND AND OBJECTIVE: Few studies have analysed a large number of patients with necrotizing pneumonia (NP) diagnosed based on computed tomography (CT) scans. The aim of the present study was to document the incidence and clinical features of NP in patients with community-acquired pneumonia (CAP). METHODS: This retrospective study was conducted on CAP patients who had been admitted to a tertiary referral centre and who had available enhanced CT scan images. Patients were allocated into NP and non-NP groups, and they were compared with respect to various clinical variables. RESULTS: Of the 830 patients included in the present study, necrotizing change was observed in 103 patients (12%). Patients with NP experienced more symptoms of pneumonia, had higher blood levels of inflammatory markers and more often required pleural drainage compared to patients with non-NP. Although the use of mechanical ventilation, vasopressor infusion, 30-day mortality, in-hospital mortality and clinical deterioration did not differ between the NP and non-NP groups, the median length of hospital stay (LOS) was significantly longer in the NP group. Multivariate analysis using Cox proportional hazards model showed that necrotizing change independently predicted LOS in patients with CAP. CONCLUSION: NP affects approximately one-tenth of hospitalized CAP patients. It may be associated with more severe clinical manifestations and may increase the need for pleural drainage. NP was found to be an independent predictor of LOS, but not of mortality in CAP patients.


Assuntos
Infecções Comunitárias Adquiridas/diagnóstico por imagem , Pulmão/patologia , Pneumonia/diagnóstico por imagem , Idoso , Infecções Comunitárias Adquiridas/complicações , Drenagem , Feminino , Mortalidade Hospitalar , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Necrose/diagnóstico por imagem , Necrose/etiologia , Pleura/cirurgia , Pneumonia/complicações , Estudos Retrospectivos , Avaliação de Sintomas , Tomografia Computadorizada por Raios X
19.
Respiration ; 93(4): 271-278, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28196360

RESUMO

BACKGROUND: Data regarding pleural effusion due to pulmonary embolism (PE) are limited. OBJECTIVES: The aim of this study was to investigate the clinical characteristics of PE patients with pleural effusion caused by PE. METHODS: Patients with PE were retrospectively analyzed and divided into 2 groups based on computed tomography: a group with pleural effusion due to PE (effusion group) and a group without pleural effusion (control group). Clinical characteristics were compared between the 2 groups. RESULTS: The study population consisted of the effusion group (n = 127) and the control group (n = 651). Serum C-reactive protein (CRP) level was significantly higher in the effusion group than in the control group. The percentages of high-risk Simplified PE Severity Index (57 vs. 47%, p = 0.008), central PE (84 vs. 73%, p = 0.013), right ventricular dilation (45 vs. 36%, p = 0.053), and pulmonary infarction (40 vs. 8%, p < 0.001) were higher in the effusion group than in the control group. Multivariate analysis demonstrated that pulmonary infarction (odds ratio [OR] 6.20, 95% confidence interval [CI] 3.49-10.91, p < 0.001) and CRP level (OR 1.05, 95% CI 1.101-1.09, p = 0.023) were independent predictors of pleural effusion due to PE. The presence of pleural effusion was not a predictor of short-term outcomes or length of hospital stay. CONCLUSIONS: Patients with more severe PE are likely to have pleural effusion caused by PE. However, pleural effusion was not a proven predictor of short-term outcome or length of hospital stay. Pulmonary infarction and CRP levels were independent risk factors for the development of pleural effusion.


Assuntos
Derrame Pleural/etiologia , Embolia Pulmonar/complicações , Adulto , Idoso , Biomarcadores/sangue , Proteína C-Reativa/análise , Mortalidade Hospitalar , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Embolia Pulmonar/sangue , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/mortalidade , Infarto Pulmonar/etiologia , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X
20.
J Korean Med Sci ; 32(4): 700-703, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28244300

RESUMO

The cause of death in patients with tuberculosis (TB) may differ according to the phase of anti-tuberculosis treatment. However, there are limited data regarding this issue in Korea. We compared the cause of death of TB patients who died during the early intensive and late continuation phase of treatment. Twenty (56%) of the 36 early deaths were due to TB-related causes, whereas 34 (89%) of the 38 late deaths were due to TB-unrelated causes. This finding suggests that TB-related early deaths mainly attributable to delayed diagnosis should be improved to further reduce the overall TB deaths.


Assuntos
Tuberculose/mortalidade , Idoso , Idoso de 80 Anos ou mais , Antituberculosos/uso terapêutico , Causas de Morte , Diagnóstico Tardio , Feminino , Humanos , Masculino , República da Coreia , Fatores de Risco , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico
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