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1.
Cancer Med ; 13(14): e70035, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39031010

RESUMO

INTRODUCTION: The prognostic capability of targeted sequencing of primary tumors in patients with estrogen receptor-positive, human epidermal growth factor receptor-2-negative early-stage invasive breast cancer (EBC) in a real-world setting is uncertain. Therefore, we aimed to determine the correlation between a 22-gene mutational profile and long-term survival outcomes in patients with ER+/ERBB2- EBC. PATIENTS AND METHODS: A total of 73 women diagnosed with ER+/ERBB2- EBC between January 10, 2004, and June 2, 2008, were followed up until December 31, 2022. Univariate and multivariate Cox models were constructed to plot the relapse-free survival (RFS) and overall survival (OS). The log-rank test derived p-value was obtained. For external validation, we performed a survival analysis of 1163 comparable patients retrieved from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset. RESULTS: At follow-up, 16 (21.9%) patients had relapsed, while 21 (nearly 29%) harbored mutant genes. Thirty-three missense mutations were detected in 14 genes. The median ages were 51 and 46 years in patients with and without mutations, respectively. Patients with any mutation had a 1.85-fold higher risk of relapse (hazard ratio [HR]: 1.85, 95% confidence interval [CI]: 0.60-5.69) compared to those without any mutation. Patients who harbored any of the six genes (MAP2K4, FGFR3, APC, KIT, RB1, and PTEN) had a nearly 6-fold increase in the risk of relapse (HR: 5.82, 95% CI: 1.31-18.56; p = 0.0069). Multivariate Cox models revealed that the adjusted HR for RFS and OS were 6.67 (95% CI: 1.32-27.57) and 8.31 (p = 0.0443), respectively. METABRIC analysis also demonstrated a trend to significantly worse RFS (p = 0.0576) in the subcohort grouped by having a mutation in any of the six genes. CONCLUSIONS: Our single-institution tissue bank study of Taiwanese women with ER+/ERBB2- EBC suggests that a novel combination of six gene mutations might have prognostic capability for survival outcomes.


Assuntos
Neoplasias da Mama , Mutação , Receptor ErbB-2 , Receptores de Estrogênio , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Pessoa de Meia-Idade , Receptores de Estrogênio/metabolismo , Prognóstico , Adulto , Estadiamento de Neoplasias , Biomarcadores Tumorais/genética , Idoso , Invasividade Neoplásica
2.
SAGE Open Med Case Rep ; 12: 2050313X241253471, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38741602

RESUMO

Head and neck mucosal melanoma is a rare but highly aggressive malignant tumor that usually has a poor prognosis. We describe a 53-year-old male patient, having no any medical history, with left maxillary sinus mucosal melanoma causing bilateral lung metastasis. Rapid tumor regrowth was observed on the 49th day after radical tumor resection. Subsequent pembrolizumab immunotherapy initially elicited pseudoprogression, for which add-on radiation therapy was carried out during maintenance pembrolizumab. A gradual decrease in tumor volume and complete remission were observed by a series of magnetic resonance imaging scans and lung windows of a computer tomography scan of chest. At the 29-month follow-up, the patient was rendered disease-free. In conclusion, head and neck mucosal melanoma may regrow rapidly after surgical resection and pseudoprogression could be frightening during immunotherapy. Subsequent single-agent pembrolizumab plus localized radiation therapy aiming to release more tumor antigens may offer the possibility of long-term remission.

3.
Sci Rep ; 12(1): 20799, 2022 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-36460770

RESUMO

Particulate matter and volatile organic compounds, including total hydrocarbons (THCs), are major ambient air pollutants. Primary nonmethane hydrocarbons (NMHCs) originate from vehicle emissions. The association between air pollution and urinary bladder cancer (UBC) is debatable. We investigated whether long-term exposure to ambient hydrocarbons increases UBC risk among people aged ≥ 20 years in Taiwan. Linkage dataset research with longitudinal design was conducted among 589,135 initially cancer-free individuals during 2000-2013; 12 airborne pollutants were identified. Several Cox models considering potential confounders were employed. The study outcomes were invasive or in situ UBC incidence over time. The targeted pollutant concentration was divided into three tertiles: T1/T2/T3. The mean age of individuals at risk was 42.5 (SD 15.7), and 50.5% of the individuals were men. The mean daily average over 10 years of airborne THC concentration was 2.25 ppm (SD 0.13), and NMHC was 0.29 ppm (SD 0.09). Both pollutants show long-term monotonic downward trend over time using the Mann-Kendall test. There was a dose-dependent increase in UBC at follow-up. UBC incidence per 100,000 enrollees according to T1/T2/T3 exposure to THC was 60.9, 221.2, and 651.8, respectively; it was 170.0/349.5/426.7 per 100,000 enrollees, corresponding to T1/T2/T3 exposure to NMHC, respectively. Without controlling for confounding air pollutants, the adjusted hazard ratio (adj.HR) was 1.83 (95% CI 1.75-1.91) per 0.13-ppm increase in THC; after controlling for PM2.5, adj.HR was even higher at 2.09 (95% CI 1.99-2.19). The adj.HR was 1.37 (95% CI 1.32-1.43) per 0.09-ppm increase in ambient NMHC concentration. After controlling for SO2 and CH4, the adj.HR was 1.10 (95% CI 1.06-1.15). Sensitivity analyses showed that UBC development risk was not sex-specific or influenced by diabetes status. Long-term exposure to THC and NMHC may be a risk factor for UBC development. Acknowledging pollutant sources can inform risk management strategies.


Assuntos
Poluentes Atmosféricos , Poluentes Ambientais , Neoplasias da Bexiga Urinária , Feminino , Humanos , Masculino , Poluentes Atmosféricos/efeitos adversos , Hidrocarbonetos/efeitos adversos , Incidência , Neoplasias da Bexiga Urinária/induzido quimicamente , Neoplasias da Bexiga Urinária/epidemiologia
4.
Artigo em Inglês | MEDLINE | ID: mdl-35437353

RESUMO

Introduction: Only a proportion of triple-negative breast cancer (TNBC) is immunotherapy-responsive. We hypothesized that the tumor microenvironment (TME) influences the outcomes of TNBC and investigated the relevant signaling pathways. Materials and Methods: Immune score (IS) and stromal score (SS) were calculated using the ESTIMATE and correlated with the overall survival (OS) in TNBC. RNA-seq data from 115 TNBC samples and 112 normal adjacent tissues were retrieved. Validations in the methylation levels in 10 TNBC and five non-TNBC cell lines were obtained. Cox model overall survival (OS) validated the derived transcription factor (TF) genes in cBioPortal breast cancer patients. Results: SS-low predicts a higher OS compared with SS-high patients (P = 0.0081 IS-high/SS-low patients had better OS (P = 0.045) than IS-low/SS-high patients. More macrophages were polarized to the M2 state in patients with IS-low/SS-high patients (P < 0.001). Moreover, CIBERSORTx showed more CD8+ cytotoxic T-cells in IS-high/SS-low patients (p = 0.0286) and more resting NK cells in the IS-low/SS-high TME (P = 0.0108). KEGG pathway analysis revealed that overexpressed genes were enriched in the IL-17 and cytokine-cytokine receptor interaction pathways. The lncRNA DRAIC, a tumor suppressor, was consistently deactivated in the 10 TNBC cell lines. On the cBioPortal platform, we validated that 13% of ER-negative, HER2-unamplified BC harbored IL17RA deep deletion and 25% harbored TRAF3IP2 amplification. On cBioPortal datasets, the nine altered TF genes derived from the X2K analysis showed significantly worse relapse-free survival in 2377 patients and OS in 4819 invasive BC patients than in the unaltered cohort. Conclusion: Of note, the results of this integrated in silico study can only be generalized to approximately 17% of patients with TNBC, in which infiltrating stromal cells and immune cells play a determinant prognostic role.

5.
Breast Cancer Res Treat ; 193(2): 361-379, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35348974

RESUMO

BACKGROUND: Invasive lobular carcinoma (ILC) treatment is similar to invasive ductal carcinoma (IDC; now invasive carcinoma-no special type, IBC-NST), based on its intrinsic subtype. However, further investigation is required for an integrative understanding of differentially perturbed molecular patterns and pathways in these histotypes. METHODS: A dataset of 780 IDC and 201 ILC samples from the TCGA-BRCA project for cross-platform multi-omics was analyzed. We leveraged a consensus approach integrating different bioinformatic algorithms to analyze mutations, CNAs, mRNA, miRNA abundance, methylation, and protein abundance to understand the complex crosstalks that distinguish ILC and IDC samples. A histotype-matched comparison was performed. We performed Cox survival analyses for prognosis based on our identified 53 histotype-specific and four discordant genes. RESULTS: Approximately 90% of ILC cases were of the luminal subtype. Somatic mutations in CDH1 were higher in ILC than in IDC (FDR-adjusted p < 0.01). Fifty-three significant oncogenic or tumor-suppressive DEGs were identified in a single histotype. PPAR signaling and lipolysis regulation in adipocytes were significantly enriched in ILC tumors. CDH1 protein had the highest differential abundance (AUC: 0.85). Moreover, BTG2, GSTA2, GPR37L1, and PGBD5 amplification was associated with poorer OS in ILC compared with no alteration. RIMS2, NACA4P, MYC, ZFPM2, and POU5F1B amplification showed a lower overall survival in patients with IDC. miR-195 showed an IDC-specific downregulation, causing overexpression of CCNE1. Integrative multi-omics supervised analysis identified 296 differentially expressed genes that successfully distinguished IDC and ILC histotypes. CONCLUSIONS: Our findings identify novel molecular candidates that potentially drive and modify the disease differentially among these histotypes.


Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Lobular , Proteínas Imediatamente Precoces , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Feminino , Humanos , Prognóstico , Receptores Acoplados a Proteínas G , Análise de Sobrevida , Proteínas Supressoras de Tumor
6.
Breast Cancer Res Treat ; 189(3): 665-676, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34553296

RESUMO

PURPOSE: Neratinib, an irreversible pan-HER tyrosine kinase inhibitor, has demonstrated systemic efficacy and intracranial activity in various stages of HER2+breast cancer. NALA was a phase III randomized trial that assessed the efficacy and safety of neratinib+capecitabine (N+C) against lapatinib+capecitabine (L+C) in HER2+ metastatic breast cancer (mBC) patients who had received ≥ 2 HER2-directed regimens. Descriptive analysis results of the Asian subgroup in the NALA study are reported herein. METHODS: 621 centrally assessed HER2+ mBC patients were enrolled, 202 of whom were Asian. Those with stable, asymptomatic brain metastases (BM) were eligible for study entry. Patients were randomized 1:1 to N (240 mg qd) + C (750 mg/m2 bid, day 1-14) with loperamide prophylaxis or to L (1250 mg qd) + C (1000 mg/m2 bid, day 1-14) in 21-day cycles. Co-primary endpoints were centrally assessed progression-free survival (PFS) and overall survival (OS). Secondary endpoints included time to intervention for central nervous system (CNS) disease, objective response rate, duration of response (DoR), clinical benefit rate, and safety. RESULTS: 104 and 98 Asian patients were randomly assigned to receive N+C or L+C, respectively. Median PFS of N+C and L+C was 7.0 and 5.4 months (P = 0.0011), respectively. Overall cumulative incidence of intervention for CNS disease was lower with N+C (27.9 versus 33.8%; P = 0.039). Both median OS (23.8 versus 18.7 months; P = 0.185) and DoR (11.1 versus 4.2 months; P < 0.0001) were extended with N+C, compared to L+C. The incidences of grade 3/4 treatment emergent adverse events (TEAEs) and TEAEs leading to treatment discontinuation were mostly comparable between the two arms. Diarrhea and palmar-plantar erythrodysesthesia were the most frequent TEAEs in both arms, similar to the overall population in incidence and severity. CONCLUSION: Consistent with the efficacy profile observed in the overall study population, Asian patients with HER2+ mBC, who had received ≥ 2 HER2-directed regimens, may also benefit from N+C. No new safety signals were noted. CLINICAL TRIAL REGISTRATION: NCT01808573.


Assuntos
Neoplasias da Mama , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Capecitabina/uso terapêutico , Feminino , Humanos , Lapatinib/uso terapêutico , Quinolinas , Receptor ErbB-2/genética , Resultado do Tratamento
7.
J Exp Clin Cancer Res ; 40(1): 119, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33794967

RESUMO

The circadian system temporally regulates physiology to maintain homeostasis. Co-opting and disrupting circadian signals appear to be distinct attributes that are functionally important for the development of a tumor and can enable or give rise to the hallmarks that tumors use to facilitate their initiation, growth and progression. Because circadian signals are also strong regulators of immune cell proliferation, trafficking and exhaustion states, they play a role in how tumors respond to immune-based cancer therapeutics. While immuno-oncology has heralded a paradigm shift in cancer therapeutics, greater accuracy is needed to increase our capability of predicting who will respond favorably to, or who is likely to experience the troubling adverse effects of, immunotherapy. Insights into circadian signals may further refine our understanding of biological determinants of response and help answer the fundamental question of whether certain perturbations in circadian signals interfere with the activity of immune checkpoint inhibitors. Here we review the body of literature highlighting circadian disruption as a cancer promoter and synthesize the burgeoning evidence suggesting circadian signals play a role in how tumors respond to immune-based anti-cancer therapeutics. The goal is to develop a framework to advance our understanding of the relationships between circadian markers, cancer biology, and immunotherapeutics. Bolstered by this new understanding, these relationships may then be pursued in future clinical studies to improve our ability to predict which patients will respond favorably to, and avoid the adverse effects of, traditional and immune-based cancer therapeutics.


Assuntos
Relógios Circadianos/imunologia , Imunoterapia/métodos , Neoplasias/terapia , Humanos , Neoplasias/imunologia
8.
Front Oncol ; 11: 564799, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33816221

RESUMO

INTRODUCTION: The acquired resistance mechanisms in patients with epidermal growth factor receptor (EGFR)-mutant lung cancer, particularly adenocarcinoma (ADC), following treatment with an EGFR tyrosine kinase inhibitor (TKI) have received extensive investigations. The phenotypic transformation to small cell carcinoma (SCCT) has been estimated to occur in approximately 3 to 10% of patients treated with an EGFR-TKI. The prognosis after SCCT is extremely poor. CASE STUDY: We report about SCCT that occurred 45 months after the initial diagnosis of ADC in an East Asian never-smoker woman with advanced-stage EGFR Del-19-mutant lung ADC treated with combined chemoradiotherapy before the era of insurance coverage for EGFR-TKIs in this country and subsequently gefitinib; deletion at codon 746-750 in exon 19 of the EGFR gene was ascertained in the original formalin-fixed paraffin-embedded lung biopsy tissue. Spinal cord compression at thoracic-12 level from SCCT was successfully relieved with neurosurgical treatment, chemotherapy with etoposide and cisplatin, and radiotherapy, while gefitinib treatment was maintained. Eleven months later, SCCT relapsed in the lung parenchyma, which was resected and was found to be sensitive to second-line weekly topotecan. Prophylactic cranial irradiation was subsequently administered. SCCT was confirmed by MALDI-TOF MS analysis of formalin-fixed paraffin-embedded tissues demonstrating the same exon 19 deletion. At the 12th-year follow-up, the patient remains relapse free with very good performance status. The novelty of this case is the successful interdisciplinary team effort to correct the spinal cord compression by maintaining the patient in an ambulatory state, non-stop use of gefitinib justified by the presence of activating EGFR mutation in SCCT tumor cells, and aggressive dose-intensive chemotherapy and radiotherapy for the SCCT that leads to an unprecedented prolonged remission and survival. This case also supports the observation that SCCT is chemotherapy sensitive, and thus, re-biopsy or complete tumor excision is recommended to understand the mutation profiles of the current tumor. Aggressive prudent administration of systemic chemotherapy obtaining optimal dose intensity leads to the successful management of the patient.

10.
Aging (Albany NY) ; 13(3): 3573-3587, 2021 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-33429365

RESUMO

Inflammation is considered as a key pathogenesis factor of dementia and epilepsy. However, epilepsy's association with dementia, particularly its role in the development of dementia, remains unclear. To evaluate the association between epilepsy and the risk of dementia, in Taiwan, we have now conducted a retrospective cohort study comprising 675 individuals (age, ≥50 years) with epilepsy and 2,025 matched control subjects without epilepsy. In order to match individuals diagnosed with epilepsy with those with no diagnosis of epilepsy (comparison cohort), we utilized exact matching at a ratio of 1:3. Compared with those in the comparison cohort, individuals in the epilepsy cohort had a significantly increased risk of developing dementia (adjusted hazard ratio = 2.87, p < 0.001). A similar result has been observed after stratifying for sex (adjusted hazard ratio in males = 2.95, p < 0.001; adjusted hazard ratio in females = 2.66, p < 0.001). To conclude, based on these data, epileptic individuals ≥50 years were at a greater risk of developing dementia than people who do not have epilepsy, which indicates that a diagnosis of epilepsy presents a greater risk for the development of dementia.


Assuntos
Demência/epidemiologia , Epilepsia/epidemiologia , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Transtornos Cerebrovasculares/epidemiologia , Estudos de Coortes , Comorbidade , Traumatismos Craniocerebrais/epidemiologia , Depressão/epidemiologia , Feminino , Humanos , Hipertensão/epidemiologia , Hepatopatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia
11.
Int J Nanomedicine ; 15: 8019-8036, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33116515

RESUMO

Exosomes are a subset of tiny extracellular vesicles manufactured by all cells and are present in all body fluids. They are produced actively in tumor cells, which are released and utilized to facilitate tumor growth. Their characteristics enable them to assist major cancer hallmarks, leveraged by cancer cells in fostering cancer growth and spread while implementing ways to escape elimination from the host environment. This review updates on the latest progress on the roles of cancer-derived exosomes, of 30-100 nm in size, in deregulating paracrine trafficking in the tumor microenvironment and circulation. Thus, exosomes are being exploited in diagnostic biomarker development, with its potential in clinical applications as therapeutic targets utilized in exosome-based nanoparticle drug delivery strategies for cancer therapy. Ongoing studies were retrieved from PubMed® and Scopus database and ClinicalTrials.gov registry for review, highlighting how cancer cells from entirely different cell lines rely on genetic information carried by their exosomes for homotypic and heterotypic intercellular communications in the microenvironment to favor proliferation and invasion, while establishing a pre-metastatic niche in welcoming cancer cells' arrival. We will elaborate on the trafficking of tumor-derived exosomes in fostering cancer proliferation, invasion, and metastasis in hematopoietic (leukemia and myeloma), epithelial (breast cancer), and mesenchymal (soft tissue sarcoma and osteosarcoma) cancers. Cancer-derived exosomal trafficking is observed in several types of liquid or solid tumors, confirming their role as cancer hallmark enabler. Their enriched genetic signals arising from their characteristic DNA, RNA, microRNA, and lncRNA, along with specific gene expression profiles, protein, or lipid composition carried by the exosomal cargo shed into blood, saliva, urine, ascites, and cervicovaginal lavage, are being studied as a diagnostic, prognostic, or predictive cancer biomarker. We reveal the latest research efforts in exploiting the use of nanoparticles to improve the overall cancer diagnostic capability in the clinic.


Assuntos
Biomarcadores Tumorais/metabolismo , Exossomos/patologia , Neoplasias/metabolismo , Neoplasias/patologia , Humanos , Neoplasias/tratamento farmacológico
12.
Front Oncol ; 10: 268, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32185135

RESUMO

Starting in 2014, large phase III clinical trials began to disclose the study results of using programmed death (PD)-1 immune checkpoint inhibitors (ICIs) (pembrolizumab, nivolumab) and PD-ligand (L)1 (atezolizumab, durvalumab, avelumab) ICIs immunotherapy in patients with advanced head and neck squamous cell carcinoma (HNSCC). In the recurrent and metastatic (R/M), cisplatin-refractory setting, nivolumab achieved a 2.2-fold increase of the median 1-year overall survival as compared with investigators' choice of salvage chemotherapy (36.0 vs. 16.6%). A paradigm shift to the winning regimen, pembrolizumab combined with platinum and infusional fluorouracil, has outperformed the past gold standard of cetuximab-based platinum and fluorouracil combination in terms of overall survival (median, 13.6 vs. 10.1 mo) when administered as the first-line treatment for R/M HNSCC. Nevertheless, many patients still did not respond to the PD-1/PD-L1 checkpoint inhibitor treatment, indicating innate, adapted, or quickly acquired resistance to the immunotherapy. The mechanisms of resistance to ICIs targeting the PD-1/PD-L1 signaling pathway in the context of HNSCC are the focus of this review. The past 5 years have seen improved understanding of the mechanisms underlying checkpoint inhibition resistance in tumor cells, such as: tumor cell adaption with malfunction of the antigen-presenting machinery via class I human leukocyte antigen (HLA), reintroduction of cyclin D-cyclin-dependent kinase (CDK) 4 complex to cell cycles, enrichment of CD44+ cancer stem-like cells, or development of inactivating mutation in IKZF1 gene; impairment of T-cell functions and proliferation through mutations in the interferon-γ-regulating genes, suppression of the stimulator of interferon genes (STING) pathway, or resulted from constitutional nutritional iron deficiency state; metabolic reprogramming by cancer cells with changes in metabolites such as GTP cyclohydrolase 1, tetrahydrobiopterin, kynurenine, indoleamine 2,3-dioxygenase, and arginase 1; defective dendritic cells, CD-69 sufficient state; and the upregulation or activation of the alternative immune checkpoints, including lymphocyte activation gene-3 (LAG3), T-cell immunoglobulin and ITIM domain (TIGIT)/CD155 pathway, T-cell immunoglobulin mucin-3 (TIM-3), and V domain-containing Ig suppressor of T-cell activation (VISTA). Several potential biomarkers or biosignatures, which could predict the response or resistance to the PD-1/PD-L1 checkpoint immunotherapy, are also discussed.

13.
PLoS One ; 14(12): e0225363, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31800599

RESUMO

Exposure to air pollutants is known to have adverse effects on human health; however, little is known about the association between hydrocarbons in air and an ischemic stroke (IS) event. We investigated whether long-term exposure to airborne hydrocarbons, including volatile organic compounds, increased IS risk. This retrospective cohort study included 283,666 people aged 40 years or older in Taiwan. Cox proportional hazards regression analysis was used to fit single- and multiple-pollutant models for two targeted pollutants, total hydrocarbons (THC) and nonmethane hydrocarbons (NMHC), and estimated the risk of IS. Before controlling for multiple pollutants, hazard ratios (HRs) of IS with 95% confidence intervals for the overall population were 2.69 (2.64-2.74) at 0.16-ppm increase in THC and 1.62 (1.59-1.66) at 0.11-ppm increase in NMHC. For the multiple-pollutant models controlling for PM2.5, the adjusted HR was 3.64 (3.56-3.72) for THC and 2.21 (2.16-2.26) for NMHC. Our findings suggest that long-term exposure to THC and NMHC may be a risk factor for IS development.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Isquemia Encefálica/epidemiologia , Hidrocarbonetos/efeitos adversos , Exposição por Inalação/estatística & dados numéricos , Acidente Vascular Cerebral/epidemiologia , Adulto , Idoso , Feminino , Humanos , Incidência , Exposição por Inalação/efeitos adversos , Masculino , Pessoa de Meia-Idade , Taiwan
14.
PLoS One ; 14(9): e0222895, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31550294

RESUMO

This study aimed to investigate whether long-term exposure to airborne hydrocarbons, including volatile organic compounds, increases the risk of developing retinal vein occlusion (RVO) among the population of Taiwan. A retrospective cohort study involving 855,297 people was conducted. Cox proportional hazards regression analysis fitted the multiple pollutant models for two targeted pollutants, including total hydrocarbons (THC), nonmethane hydrocarbons (NMHC) were used, and the risk of RVO was estimated. The chi-squared test and one-way analysis of variance were used to test differences in demographics and comorbidity distribution among tertiles of the targeted pollutants. Before controlling for multiple pollutants, hazard ratios for the overall population were 19.88 (95% CI: 17.56-22.50) at 0.51-ppm increases in THC and 4.33 (95% CI: 3.97-4.73) at 0.27-ppm increases in NMHC. The highest adjusted hazard ratios for different multiple pollutant models of each targeted pollutant were statistically significant (all p values were ≤0.05) for all patients at 29.67 (95% CI: 25.57-34.42) for THC and 16.24 (95% CI: 14.14-18.65) for NMHC. Our findings suggest that long-term exposure to THC and NMHC contribute to RVO development.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/efeitos adversos , Oclusão da Veia Retiniana/epidemiologia , Adolescente , Adulto , Poluição do Ar/estatística & dados numéricos , Criança , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Humanos , Hidrocarbonetos/efeitos adversos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Oclusão da Veia Retiniana/etiologia , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia , Fatores de Tempo , Adulto Jovem
15.
Environ Health Insights ; 13: 1178630219862236, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31367176

RESUMO

BACKGROUND: A limited number of potentially hazardous trace elements were quantified in the aquatic environment near the world's second largest coal-fired power plant (CFPP) and the coal combustion residual (CCR) disposition sites in Central Taiwan. We postulated that contamination from specific trace elements would be present in the abovementioned aquatic environments. METHODS: Cross-sectional sampling of trace elements was first performed between September 24, 2017 and October 3, 2017 outside the CFPP, in the effluent sampled from Changhua, a county south of metropolitan Taichung, and at the historical CCR disposal sites, using the intertidal zone surface seawater and the seawater in an oyster farm as controls. Aqueous samples were collected from 12 locations for analysis of 13 trace elements (Al, As, B, Cd, total Cr, Co, Fe, Pb, Mn, Se, Sr, Tl, and V). We used inductively coupled plasma (ICP) optical emission spectrometry to determine B and Fe levels, and ICP mass spectrometry for all other trace elements. The Spearman rank correlation coefficient (Rho) was calculated to examine the pairwise relation among the trace elements. RESULTS: Al (50% of all samples), B (66.7%), Fe (25%), Mn (50%), Sr (8.3%), and V (25%) were identified as being above the Environmental Protection Agency (EPA) regulation limit. The oyster farm seawater had no concerns. Mn (96.4 µg/L) in the CFPP drainage effluent was 1.9-fold above the regulation limit. Fe, Mn, and V were detected from the cooling channel at 4379, 625, and 11.3 µg/L, respectively. The effluent and water from the areas surrounding the 2 CCR dump sites revealed similar magnitudes of trace element contamination. B is highly correlated with Sr (Rho = 0.94, 95% confidence interval [CI], 0.80-0.98). Meanwhile, Fe is highly correlated with Al (Rho = 0.77), Pb (Rho = 0.71), Co (Rho = 0.75), and V (Rho = 0.84). CONCLUSIONS: The EPA must set an explicit regulation limit for aluminum, boron, iron, and strontium in the aquatic environment. This exploratory research will inform policymaking regarding certain trace elements that could potentially have an adverse impact on public health and wildlife.

16.
Cancers (Basel) ; 11(7)2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31311148

RESUMO

We hypothesized that sorafenib plus transarterial chemoembolization (TACE) would confer survival benefits over sorafenib alone for advanced hepatocellular carcinoma (aHCC). We investigated this while using the population-based All-Cancer Dataset to assemble a cohort (n = 3674; median age, 60; 83% men) of patients receiving sorafenib for aHCC (Child-Pugh A) with macro-vascular invasion or nodal/distant metastases. The patients were classified into the sorafenib-TACE group (n = 426) or the propensity score-matched sorafenib-alone group (n = 1686). All of the participants were followed up until death or the end of the study. Time-dependent Cox model and the Mantel-Byar test were used for survival analysis. During the median follow-ups of 221 and 133 days for the sorafenib-TACE and sorafenib-alone groups, 164 (39%) and 916 (54%) deaths occurred, respectively; the corresponding median overall survivals (OS) were 381 and 204 days, respectively (hazard ratio, HR: 0.74; 95% confidence interval, CI, 0.63-0.88; p = 0.021). The one-year and six-month OS were 53.5% and 80.3% in the sorafenib-TACE group and 32.4% and 54.4% in the sorafenib-alone group, respectively. The major complications were comparable between the two groups. The addition of TACE to sorafenib improves survival, with a 26% reduction in mortality. These findings provide strong real-world evidence that supports this combination strategy for eligible Child-Pugh A aHCC patients.

18.
Scand J Clin Lab Invest ; 79(1-2): 25-31, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30628465

RESUMO

Pathogenic bacteremia portends a high mortality risk in adult patients admitted to an Emergency Department (ED). This study aims to investigate the effect of adding high-sensitivity C-reactive protein (hs-CRP) to procalcitonin (PCT) and lactate in predicting bacteremia, Gram-negative (GNB) and Gram-positive bacteremia (GPB), using the optimal cutoff derived from the receiver operating characteristics analysis. We evaluated the diagnostic measures, including the positive-test likelihood (LR+), the negative-test likelihood (LR-), and the diagnostic odds ratio (DOR) using a single-center retrospective analysis design. This Standards for Reporting Diagnostic-compliant study comprised 886 consecutive adults who were admitted to the ED in 2010; to this cohort, a 22.2% prevalence of true bacteremia was subsequently confirmed. At the cutoff of 3.9 µg/L, PCT had a DOR of 5.3 (95% confidence interval [CI]: 3.76-7.61) and LR + of 2.8 (95% CI: 2.3-3.4) in predicting overall bacteremia. Elevated PCT and lactate (cutoff at 2 mmol/L), increased the DOR and LR + to 6.3 (95% CI: 4.27-9.29) and 4.0 (95% CI: 3.1-5.2). The DOR and LR + were further improved to 7.1 (95% CI: 4.2-11.95) and 5.6 (95% CI: 3.7-8.6), respectively, when hs-CRP at the cutoff of 1238 nmol/L was added to PCT plus lactate. High-sensitivity CRP at the cutoff of 1,255 nmol/L can enhance the discriminative power raising DOR and LR + values for GPB. The elevation of hs-CRP at the optimal cutoff might improve the diagnostic performance to predict unspecified bacteremia and GPB, but not GNB.


Assuntos
Bacteriemia/diagnóstico , Proteína C-Reativa/metabolismo , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Positivas/diagnóstico , Ácido Láctico/sangue , Pró-Calcitonina/sangue , Adulto , Idoso , Bacteriemia/sangue , Bacteriemia/microbiologia , Bacteriemia/patologia , Biomarcadores/sangue , Serviço Hospitalar de Emergência , Feminino , Infecções por Bactérias Gram-Negativas/sangue , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/patologia , Infecções por Bactérias Gram-Positivas/sangue , Infecções por Bactérias Gram-Positivas/microbiologia , Infecções por Bactérias Gram-Positivas/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Curva ROC , Estudos Retrospectivos
19.
Curr Alzheimer Res ; 16(14): 1276-1289, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31902365

RESUMO

BACKGROUND: Alzheimer's disease, the most common cause of dementia among the elderly, is a progressive and irreversible neurodegenerative disease. Exposure to air pollutants is known to have adverse effects on human health, however, little is known about hydrocarbons in the air that can trigger a dementia event. OBJECTIVE: We aimed to investigate whether long-term exposure to airborne hydrocarbons increases the risk of developing dementia. METHOD: The present cohort study included 178,085 people aged 50 years and older in Taiwan. Cox proportional hazards regression analysis was used to fit the multiple pollutant models for two targeted pollutants, including total hydrocarbons and non-methane hydrocarbons, and estimated the risk of dementia. RESULTS: Before controlling for multiple pollutants, hazard ratios with 95% confidence intervals for the overall population were 7.63 (7.28-7.99, p <0.001) at a 0.51-ppm increases in total hydrocarbons, and 2.94 (2.82-3.05, p <0.001) at a 0.32-ppm increases in non-methane hydrocarbons. The highest adjusted hazard ratios for different multiple-pollutant models of each targeted pollutant were statistically significant (p <0.001) for all patients: 11.52 (10.86-12.24) for total hydrocarbons and 9.73 (9.18-10.32) for non-methane hydrocarbons. CONCLUSION: Our findings suggest that total hydrocarbons and non-methane hydrocarbons may be contributing to dementia development.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Demência/epidemiologia , Poluição Ambiental/efeitos adversos , Hidrocarbonetos/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Taiwan
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