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BACKGROUND/AIM: Numerous studies have reported the over-expression of the radiation-sensitive protein 51 (RAD51) in various types of cancer. However, the role of RAD51 genotypes in lung cancer remains largely unknown. This study aimed to assess the impact of the common variant RAD51 rs1801320 (G-135C) genotypes on the risk of lung cancer in Taiwan. MATERIALS AND METHODS: The contribution of RAD51 rs1801320 genotypes to lung cancer risk was investigated in a cohort comprising 358 lung cancer patients and 716 age- and sex-matched healthy controls, utilizing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. RESULTS: The analysis revealed that among the control subjects, the percentages of GG, CG, and CC genotypes of RAD51 rs1801320 were 73.2%, 24.3%, and 2.5%, respectively. Among the lung cancer patients, these percentages were 71.0%, 25.1%, and 3.9%, respectively (p for trend=0.4075). Allelic frequency distributions showed no significant association between the C allele of RAD51 rs1801320 and lung cancer risk determination (p=0.2987). Specifically, the RAD51 rs1801320 CC genotypes were associated with an elevated risk of lung cancer among males [adjusted odds ratio (aOR)=2.28, 95% confidence interval (95%CI)=1.03-4.87] and smokers (aOR=2.93, 95%CI=1.23-5.87), but not among females and non-smokers. CONCLUSION: The RAD51 rs1801320 CC genotype was identified as a risk factor for elevated lung cancer risk in males and smokers. This genotype may serve as a molecular biomarker at the DNA level for early detection and prediction of lung cancer in Taiwan.
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Neoplasias Pulmonares , Masculino , Femenino , Humanos , Neoplasias Pulmonares/genética , Predisposición Genética a la Enfermedad , Taiwán/epidemiología , Polimorfismo de Nucleótido Simple , Genotipo , Factores de Riesgo , Estudios de Casos y ControlesRESUMEN
OBJECTIVES: The increasing epidemic of infections caused by drug-resistant Gram-negative bacteria has led to the development of several antibiotic therapies. Owing to the scarcity of head-to-head comparisons of current and emerging antibiotics, the present network meta-analysis aimed to compare the efficacy and safety of antibiotics in patients with nosocomial pneumonia, complicated intra-abdominal infection, or complicated urinary tract infection. METHODS: Two independent researchers systematically searched databases up to August 2022 and included 26 randomised controlled trials that fulfilled the inclusion criteria. The protocol was registered in the Prospective Register of Systematic Reviews, PROSPERO (CRD42021237798). The frequentist random effects model (R version 3.5.1, netmeta package) was utilized. The DerSimonian-Laird random effects model was used to estimate heterogeneity. The calculated P-score was applied to rank the interventions. Additionally, inconsistencies, publication bias, and subgroup effects were assessed in the present study to avoid bias. RESULTS: There was no significant difference among included antibiotics in terms of clinical response and mortality, probably because most antibiotic trials were designed to be non-inferior. In terms of P-score ranking, carbapenems may be the recommended choice considering both adverse events and clinical responses. On the other hand, for carbapenem-sparing options, ceftolozane-tazobactam was the preferred antibiotic for nosocomial pneumonia; eravacycline, for complicated intra-abdominal infection; and cefiderocol, for complicated urinary tract infection. CONCLUSION: Carbapenems may be preferable options in terms of safety and efficacy for the treatment of Gram-negative bacterial complicated infections. However, to preserve the effectiveness of carbapenems, it is important to consider carbapenem-sparing regimens.
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Infección Hospitalaria , Infecciones por Bacterias Gramnegativas , Neumonía Asociada a la Atención Médica , Infecciones Intraabdominales , Infecciones Urinarias , Humanos , Antibacterianos/efectos adversos , Carbapenémicos/uso terapéutico , Infección Hospitalaria/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Neumonía Asociada a la Atención Médica/tratamiento farmacológico , Infecciones Intraabdominales/tratamiento farmacológico , Infecciones Intraabdominales/microbiología , Metaanálisis en Red , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/microbiología , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) is a key pathogen associated with ventilator-associated pneumonia (VAP). Research on treatment outcomes, especially ventilator dependence, in patients with VAP caused by CRAB remains limited. METHODS: This retrospective multicenter study included ICU-admitted patients with VAP caused by CRAB. The original cohort was included as the mortality evaluation cohort. The ventilator dependence evaluation cohort included cases that survived more than 21 days after VAP and without prolonged ventilation before VAP onset. The mortality rate, ventilator dependence rate, clinical factors associated with treatment outcomes, and treatment outcome differences with various VAP onset times were investigated. RESULTS: In total, 401 patients with VAP caused by CRAB were analyzed. The 21-day all-cause mortality rate was 25.2%, and the 21-day ventilator dependence rate was 48.8%. Clinical factors associated with 21-day mortality included lower body mass index, higher sequential organ failure assessment score, vasopressors usage, CRAB persistence, and VAP onset time > seven days. Clinical factors associated with 21-day ventilator dependence included older age, vasopressors usage, and VAP onset time > seven days. CONCLUSIONS: ICU-admitted patients with CRAB-related VAP had high mortality and ventilator dependence rates. Older age, vasopressor usage, and longer VAP onset time were independent factors associated with ventilator dependence.
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Acinetobacter baumannii , Neumonía Asociada al Ventilador , Humanos , Neumonía Asociada al Ventilador/tratamiento farmacológico , Enfermedad Crítica , Estudios Retrospectivos , Carbapenémicos/farmacología , Carbapenémicos/uso terapéutico , Ventiladores Mecánicos/efectos adversosRESUMEN
The combination of bevacizumab or ramucirumab with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy, chemotherapy, or immunotherapy for non-small-cell lung cancer (NSCLC) patients with EGFR mutations could have survival benefits. However, no study, to date, has been conducted to compare the efficacy and safety of these two antiangiogenic therapies (AATs). Stage IIIB to IV EGFR-mutated NSCLC patients who received first-line EGFR-TKIs between January 2014 and May 2022 were enrolled. These patients were divided into two groups: those receiving bevacizumab and those receiving ramucirumab as a combination therapy in any line of treatment. Ninety-six patients were enrolled in this study's final analysis. The progression-free survival (PFS) of patients who received front-line AATs combined with EGFR-TKI therapy was longer than that of patients receiving later-line AATs combined with other therapies (19.6 vs. 10.0 months, p < 0.001). No difference in overall survival (OS) was observed between front-line and later-line therapy (non-reach vs. 44.0 months, p = 0.261). Patients who received these two different AATs did not differ in PFS (24.1 vs. 15.7 months, p = 0.454) and OS (48.6 vs. 43.0 months, p = 0.924). In addition, these two AATs showed similar frequencies of the T790M mutation (43.6% vs. 38.2%; p = 0.645). Multivariate Cox regression analysis indicated several AAT cycles as an independent good prognostic factor in OS. The incidence of some adverse events such as bleeding and hepatitis was higher for bevacizumab than for ramucirumab but it was not significant. Front-line AAT and EGFR-TKI combination therapy improved the PFS of stage IV EGFR-mutated NSCLC patients. The effectiveness and safety of the two AATs were similar.
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BACKGROUND/AIM: Triple negative breast cancer (TNBC) is one of the most challenging breast cancer types. Interleukin-8 (IL-8) is a pro-tumorigenic cytokine, promoting tumor proliferation and migration. This study aimed to examine the contribution of IL-8 rs4073 genotypes to breast cancer risk and provide a summary of related literature. MATERIALS AND METHODS: IL-8 genotypic profiles were determined among 1,232 breast cancer cases and 1,232 controls via polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The IL-8 rs4073 AT and AA genotypes had significantly lower prevalence in the case group compared to control group. Allelic frequency analysis showed that individuals carrying the A allele have relatively decreased risk for breast cancer. The stratification analysis showed that IL-8 rs4073 genotypes were protective markers for those with younger (≤55) age. CONCLUSION: IL-8 rs4073 A allele is a novel predictor for breast cancer, especially TNBC.
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Interleucina-8 , Neoplasias de la Mama Triple Negativas , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Interleucina-8/genética , Polimorfismo de Nucleótido Simple , Taiwán/epidemiología , Neoplasias de la Mama Triple Negativas/genéticaRESUMEN
BACKGROUND/AIM: The elevated expression of interleukin-18 (IL-18) among lung cancer patients raised our curiosity to examine the role of IL-18 genotypes in lung cancer. MATERIALS AND METHODS: IL-18 -656 (rs1946519), -607 (rs1946518), and -137 (rs187238) genotypes of 358 lung cancer cases and 716 controls were determined via the PCR-RFLP methodology. RESULTS: The distributions of genotypic and allelic frequencies of IL-18 -607, but not those of -656 or -137, were differentially distributed between cases and controls. IL-18 -607 AC and CC genotypes were both lower (45.8% and 16.2%) in lung cancer patients compared to controls (51.4% and 24.7%). In addition, IL-18 -607 AC and CC genotypes were of significantly lower percentages both among non-smokers and smokers. Otherwise, no differential distribution was found regarding IL-18 -656 or -137. CONCLUSION: IL-18 -607 C allele can serve as a protective predictor for lung cancer risk in Taiwanese.
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Interleucina-18 , Neoplasias Pulmonares , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Interleucina-18/genética , Neoplasias Pulmonares/genética , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: The treatment options for epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) with brain metastases (BMs) include EGFR-tyrosine kinase inhibitors (TKIs), stereotactic radiosurgery (SRS), whole-brain radiotherapy, brain surgery, and antiangiogenesis therapy. As treatment options evolve, redefining optimal treatment strategies to improve survival are crucial. METHODS: A total of 150 EGFR-mutant NSCLC patients with BMs who received first- or second-generation EGFR-TKIs as first-line treatment between January 2012 and October 2019 were included in this analysis. RESULTS: After multivariate analysis, patients with the graded prognostic assessment for lung cancer using molecular markers (Lung-mol GPA) ≥3 (hazard ratio [HR]: 0.538, 95% confidence interval [CI]: 0.35-0.83), who received afatinib or erlotinib as first-line treatment (HR: 0.521, 95% CI: 0.33-0.82), underwent SRS therapy (HR: 0.531, 95% CI: 0.32-0.87), or were sequentially treated with osimertinib (HR: 0.400, 95% CI: 0.23-0.71) were associated with improved overall survival (OS). Furthermore, SRS plus EGFR-TKI provided more OS benefits in patients with Lung-mol GPA ≥3 compared with EGFR-TKI alone in our patient cohort (44.9 vs. 26.7 months, p = 0.005). The OS in patients who received sequential osimertinib therapy was significantly longer than those without osimertinib treatment (43.5 vs. 24.3 months, p < 0.001), regardless of T790 mutation status (positive vs. negative vs. unknown: 40.4 vs. 54.6 vs.43.4 months, p = 0.227). CONCLUSIONS: The study demonstrated that EGFR-mutant NSCLC patients with BMs could be precisely treated with SRS according to Lung-mol GPA ≥3. Sequential osimertinib was associated with prolonged survival, regardless of T790M status.
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Neoplasias Encefálicas , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/secundario , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Mutación , Inhibidores de Proteínas Quinasas/uso terapéutico , TaiwánRESUMEN
BACKGROUND/AIM: Chronic inflammation is believed to play a critical role in the pathogenesis of lung cancer. Interleukin-8 (IL-8) is an inflammatory cytokine and plays an important role in cancer development. Few studies have investigated the association between interleukin-8 - 251T/A (rs4073) genotype and lung cancer risk in various populations. MATERIALS AND METHODS: In the current study, genotypes of interleukin-8 rs4073 were analyzed in 358 lung cancer patients and 716 healthy controls in Taiwan, by the PCR-RFLP methodology. RESULTS: The distribution frequencies of interleukin-8 rs4073 genotypes between control and case groups were compared, and the homozygous variant AA genotypes showed a lower percentage in the case group compared to the control group (OR=0.57, 95%CI=0.39-0.85, p=0.0059). The distributions of alleles frequencies also exhibited statistical difference (p=0.0066). There was an interaction between interleukin-8 rs4073 and smoking habits (p=0.0051). CONCLUSION: Interleukin-8 rs4073 genotypes were associated with lung cancer susceptibility, especially for smokers.
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Interleucina-8/genética , Neoplasias Pulmonares/genética , Regiones Promotoras Genéticas , Anciano , Pueblo Asiatico/genética , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/etnología , Masculino , Persona de Mediana Edad , Fenotipo , Medición de Riesgo , Factores de Riesgo , Fumar/efectos adversos , Fumar/etnología , Taiwán/epidemiologíaRESUMEN
The development of third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) targeting T790M-mutant non-small cell lung cancer (NSCLC) has raised the importance of re-biopsy after EGFR-TKI failure. This study aimed to investigate the feasibility of interventional pulmonology (IP) procedures as re-biopsy methods for identifying the T790M mutation in EGFR-TKI-resistant patients. One hundred and thirty-nine NSCLC patients who underwent IP procedures for re-biopsy as their initial investigation after EGFR-TKI treatment failure were enrolled in this study between January 2020 and August 2022. All patients underwent a first re-biopsy with IP methods, with a diagnostic yield of 81.2% and T790M mutation detection rate of 36%. Thirty patients underwent a second re-biopsy; IP methods were used for 17 (56.6%) patients and non-IP methods for 13 (43.4%) patients; the T790M mutation detection rate was 36.4%. Only six patients underwent a third re-biopsy; no T790M mutation was noted. The T790M mutation detection rate did not differ between IP and non-IP methods (33.6 % vs. 37.5%, p = 0.762). In 11 cases (7.5%), a re-biopsy revealed histologic transformation from lung adenocarcinoma. IP procedures, as first-line re-biopsy methods for NSCLC, are feasible and provide sufficient tissue for identification of the resistance mechanism and target gene T790M mutation.
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Targeting protein kinase C (PKC) family was found to repress the migration and resistance of non-small cell lung cancer cells to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, none of the PKC inhibitors has been approved for anticancer therapy yet due to the limited efficacy in clinical trials, and the underlying mechanisms remain unclear. l-lactic acidosis, a common condition comprising high l-lactate concentration and acidic pH in the tumor microenvironment, has been known to induce tumor metastasis and drug resistance. In this study, l-lactic acid was found to reverse the inhibitory effects of pan-PKC inhibitors GO6983 on PKC activity, cell migration, and EGFR-TKI resistance, but these effects were not affected by the modulators of lactate receptor GPR81. Interestingly, blockade of lactate transporters, monocarboxylate transporter-1 and -4 (MCT1 and MCT4), attenuated the intracellular level of GO6983, and its inhibitory effect on PKC activity, suggesting that lactic acid promotes the resistance to PKC inhibitors by competing for the uptake through these transporters rather than by activating its receptor, GPR81. Our findings explain the underlying mechanisms of the limited response of PKC inhibitors in clinical trials.
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Acidosis Láctica , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Simportadores , Receptores ErbB/metabolismo , Humanos , Ácido Láctico/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Transportadores de Ácidos Monocarboxílicos/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Simportadores/metabolismo , Microambiente TumoralRESUMEN
The increase in incidental discovery of pulmonary nodules has led to more urgent requirement of tissue diagnosis. The peripheral pulmonary nodules are especially challenging for clinicians. There are various modalities for diagnosis and tissue sampling of pulmonary lesions, but most of these modalities have their own limitations. This has led to the development of many advanced technical modalities, which have empowered pulmonologists to reach the periphery of the lung safely and effectively. These techniques include thin/ultrathin bronchoscopes, radial probe endobronchial ultrasound (RP-EBUS), and navigation bronchoscopy-including virtual navigation bronchoscopy (VNB) and electromagnetic navigation bronchoscopy (ENB). Recently, newer technologies-including robotic-assisted bronchoscopy (RAB), cone-beam CT (CBCT), and augmented fluoroscopy (AF)-have been introduced to aid in the navigation to peripheral pulmonary nodules. Technological advances will also enable more precise tissue sampling of smaller peripheral lung nodules for local ablative and other therapies of peripheral lung cancers in the future. However, we still need to overcome the CT-to-body divergence, among other limitations. In this review, our aim is to summarize the recent advances in diagnostic bronchoscopy technology.
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BACKGROUND/AIM: The tissue inhibitor of metalloproteinase-2 (TIMP-2) is a critical inhibitor of matrix metalloproteinases (MMPs). Along with MMPs, TIMP-2 regulates the breakdown and remodeling of the extracellular matrix (ECM) and basement membranes. This study investigated the role of genotypes of the TIMP-2 -418G/C (rs8179090) single nucleotide polymorphism on lung risk. MATERIALS AND METHODS: A total of 358 lung cancer patients and 716 healthy subjects were recruited in this study. Genotypes were identified via the polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The distribution of alleles and genotype frequencies of TIMP-2 -418G/C genotypes between the two groups were compared and no statistically significant difference (p>0.05) was found. The heterozygous and homozygous variant genotypes showed no differential distribution between the control and case groups (p>0.05). CONCLUSION: TIMP-2 -418G/C variants might not be associated with lung cancer susceptibility and could not serve as predictors.
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Biomarcadores de Tumor/genética , Neoplasias Pulmonares/genética , Polimorfismo de Nucleótido Simple , Inhibidor Tisular de Metaloproteinasa-2/genética , Anciano , Estudios de Casos y Controles , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Persona de Mediana Edad , Fenotipo , Medición de Riesgo , Factores de Riesgo , TaiwánRESUMEN
Hesperidin (HD) is a common flavanone glycoside isolated from citrus fruits and possesses great potential for cardiovascular protection. Hesperetin (HT) is an aglycone metabolite of HD with high bioavailability. Through the docking simulation, HD and HT have shown their potential to bind to two cellular proteins: transmembrane serine protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2), which are required for the cellular entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our results further found that HT and HD suppressed the infection of VeroE6 cells using lentiviral-based pseudo-particles with wild types and variants of SARS-CoV-2 with spike (S) proteins, by blocking the interaction between the S protein and cellular receptor ACE2 and reducing ACE2 and TMPRSS2 expression. In summary, hesperidin is a potential TMPRSS2 inhibitor for the reduction of the SARS-CoV-2 infection.
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Tratamiento Farmacológico de COVID-19 , Hesperidina/química , Hesperidina/farmacología , SARS-CoV-2/efectos de los fármacos , Enzima Convertidora de Angiotensina 2/química , Enzima Convertidora de Angiotensina 2/metabolismo , Animales , COVID-19/metabolismo , COVID-19/virología , Línea Celular Tumoral , Chlorocebus aethiops , Proteasas Similares a la Papaína de Coronavirus/química , Proteasas Similares a la Papaína de Coronavirus/metabolismo , Humanos , Simulación del Acoplamiento Molecular , SARS-CoV-2/metabolismo , Serina Endopeptidasas/química , Serina Endopeptidasas/efectos de los fármacos , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/metabolismo , Células VeroRESUMEN
OBJECTIVES: To investigate the association between adjunctive nebulized colistin and treatment outcomes in critically ill patients with nosocomial carbapenem-resistant Gram-negative bacterial (CR-GNB) pneumonia. METHODS: This retrospective, multi-centre, cohort study included individuals admitted to the intensive care unit with nosocomial pneumonia caused by colistin-susceptible CR-GNB. Enrolled patients were divided into groups with/without nebulized colistin as adjunct to at least one effective intravenous antibiotic. Propensity score matching was performed in the original cohort (model 1) and a time-window bias-adjusted cohort (model 2). The association between adjunctive nebulized colistin and treatment outcomes was analysed. RESULTS: In total, 181 and 326 patients treated with and without nebulized colistin, respectively, were enrolled for analysis. The day 14 clinical failure rate and mortality rate were 41.4% (75/181) versus 46% (150/326), and 14.9% (27/181) versus 21.8% (71/326), respectively. In the propensity score-matching analysis, patients with nebulized colistin had lower day 14 clinical failure rates (model 1: 41% (68/166) versus 54.2% (90/166), p 0.016; model 2: 35.3% (41/116) versus 56.9% (66/116), p 0.001). On multivariate analysis, nebulized colistin was an independent factor associated with fewer day 14 clinical failures (model 1: adjusted odds ratio (aOR) 0.59, 95% CI 0.37-0.92; model 2: aOR 0.37, 95% CI 0.21-0.65). Nebulized colistin was not associated independently with a lower 14-day mortality rate in the time-dependent analysis in both models 1 and 2. CONCLUSIONS: Adjunctive nebulized colistin was associated with lower day 14 clinical failure rate, but not lower 14-day mortality rate, in critically ill patients with nosocomial pneumonia caused by colistin-susceptible CR-GNB.
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Antibacterianos/uso terapéutico , Colistina/uso terapéutico , Infecciones por Bacterias Gramnegativas , Neumonía Asociada a la Atención Médica , Neumonía Bacteriana , Carbapenémicos/uso terapéutico , Enfermedad Crítica , Farmacorresistencia Bacteriana Múltiple , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/mortalidad , Neumonía Asociada a la Atención Médica/tratamiento farmacológico , Neumonía Asociada a la Atención Médica/mortalidad , Humanos , Neumonía Bacteriana/tratamiento farmacológico , Neumonía Bacteriana/mortalidad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND/AIM: Matrix metalloproteinase 2 (MMP2) is reported to be overexpressed in asthma; however, its genotypic contribution to asthma is not well studied. Therefore, we examined the association of MMP2 genotypes with asthma risk among Taiwanese. MATERIALS AND METHODS: One hundred and ninety-eight asthma patients and 453 non-asthmatic subjects were determined with respect to their MMP2 -1306 (rs243845) and -735 (rs2285053) genotypes. RESULTS: CT and TT at MMP2 rs243845 are 17.7% and 1.5% among asthma cases, whereas their presence in healthy subjects is at 28.1% and 2.4%, respectively (p for trend=0.0118). In detail, the CT genotype in MMP2 rs243845 was associated with a decreased asthma risk [adjusted odds ratio (OR)=0.57, 95% confidence interval (CI)=0.37-0.78, p=0.0040], and the T allele conferred a significantly lower asthma risk compared to the wild-type C allele (adjusted OR=0.55, 95%CI=0.43-0.77, p=0.0042). No significance was found for MMP2 rs2285053. CONCLUSION: The genotype of CT in MMP2 rs243845 may serve as a novel biomarker in determining susceptibility to asthma in Taiwan.
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Asma , Metaloproteinasa 2 de la Matriz , Asma/epidemiología , Asma/genética , Estudios de Casos y Controles , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Metaloproteinasa 2 de la Matriz/genética , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Taiwán/epidemiologíaRESUMEN
BACKGROUND: This study aimed to evaluate the characteristics of patients with newly diagnosed advanced lung cancer who initially presented with respiratory failure. METHODS: This was a retrospective study which analyzed patients in the intensive care unit (ICU) with newly diagnosed advanced lung cancer who were placed on mechanical ventilation (MV). We defined newly diagnosed lung cancer as pathological or molecular results for treatment decisions not yet determined when the patient was admitted to ICU. RESULTS: During the 14-year inclusion period, 845 lung cancer patients requiring MV were screened. A total of 56 newly diagnosed extensive lung cancer patients were analyzed. Cancer-related to central airway obstruction (n = 29, 51.8%) was the leading cause of respiratory failure. The significant etiologies of delay in the diagnosis of lung cancer were diagnostic error, mistaking cancer for tuberculosis, and missed hilar lesions. The six-month survival rate was only 7.1% (n = 4). The sequential organ failure assessment (SOFA) score was significantly associated with mortality (HR = 1.142, 95% CI = 1.012-1.288, P = 0.031). The six-month survival rate in patients receiving suitable targeted therapy and accepting chemotherapy and best supportive care was 40% (2/5), 0% (0/7), and 4.5% (2/44), respectively. CONCLUSIONS: Patients with newly diagnosed advanced lung cancer with acute life-threatening respiratory failure have poor outcomes. Cancer-related to central airway obstruction is a leading cause of respiratory failure. Diagnostic errors such as tuberculosis and missed hilar lesions are the two main etiologies of a delay in diagnosis. The SOFA score is correlated with mortality. Targeted therapy can raise the six-month survival rates in patients with oncogenic mutation adenocarcinoma, who survive after presentation in a critical condition.
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Neoplasias Pulmonares/complicaciones , Insuficiencia Respiratoria/etiología , Anciano , Diagnóstico Tardío , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Insuficiencia Respiratoria/patología , Estudios Retrospectivos , Tasa de Supervivencia , Factores de TiempoRESUMEN
OBJECTIVE: Approximately 10%-15% patients with epidermal growth factor receptor (EGFR) mutations harbor non-classical mutations. However, the effects of EGFR-tyrosine kinases (TKIs), particularly second-generation EGFR-TKI (afatinib) compared to first-generation EGFR-TKIs (gefitinib/erlotinib), in patients with non-classical EGFR mutations remain unknown. METHODS: We conducted this retrospective study at the China Medical University Hospital (Taichung, Taiwan) from June 2011 to July 2016. Specimens from 1632 patients were tested for EGFR mutations. We surveyed the effectiveness of afatinib and gefitinib/erlotinib in stage IIIb-IV lung adenocarcinoma patients with non-classical EGFR mutations. RESULTS: Fifty-six patients with advanced-stage (stage IIIB-IV) lung adenocarcinoma with non-classical mutations and receiving EGFR-TKI treatment had completed follow-up and were further analyzed. Afatinib versus gefitinib/erlotinib showed that the objective response rates were 62.5% versus 50.0% (p=0.35). Median progression-free survival (PFS) of 11.0 versus 3.6 months (p=0.03), respectively, was observed for the 51 non-classical EGFR mutated (excluding 5 patients with exon 20 insertions) lung adenocarcinomas. Subset analysis showed that PFS curves of afatinib were more easily distinguished in non-classical EGFR mutations lacking a combination with a classical mutation (non-classical with classical complex mutations group: median PFS, 11.0 versus 8.2 months, p=0.19; non-classical mutation alone or in combination with other non-classical mutations group: median PFS, 18.3 versus 2.8 months, p=0.07). CONCLUSIONS: Afatinib may be a first-choice EGFR-TKI for patients with advanced-stage lung adenocarcinomas harboring non-classical mutations.
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Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Receptores ErbB/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Mutación , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adenocarcinoma del Pulmón , Afatinib , Anciano , Anciano de 80 o más Años , Análisis Mutacional de ADN , Clorhidrato de Erlotinib/administración & dosificación , Femenino , Gefitinib , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Quinazolinas/administración & dosificación , Estudios Retrospectivos , Resultado del TratamientoAsunto(s)
Duodeno/lesiones , Embolización Terapéutica/efectos adversos , Migración de Cuerpo Extraño/diagnóstico , Hemorragia Gastrointestinal/terapia , Anciano , Angiografía , Cateterismo Periférico , Remoción de Dispositivos/métodos , Diagnóstico Diferencial , Embolización Terapéutica/instrumentación , Endoscopía Gastrointestinal , Migración de Cuerpo Extraño/cirugía , Humanos , MasculinoRESUMEN
The title compound, [Zn(SO(4))(C(12)H(10)N(2))](n), features a layered structure based on [Zn(SO(4))](n) spirals linked by 1,2-di-4-pyridylethylene (bpe) ligands, with the tetrahedral Zn and S atoms lying on twofold axes. The bpe ligands are centrosymmetric. The layers are linked by weak C-H...O interactions.