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1.
Clin Cancer Res ; 25(6): 1786-1794, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30154229

RESUMO

PURPOSE: To establish a cohort of high-risk women undergoing intensive surveillance for breast cancer.Experimental Design: We performed dynamic contrast-enhanced MRI every 6 months in conjunction with annual mammography (MG). Eligible participants had a cumulative lifetime breast cancer risk ≥20% and/or tested positive for a pathogenic mutation in a known breast cancer susceptibility gene. RESULTS: Between 2004 and 2016, we prospectively enrolled 295 women, including 157 mutation carriers (75 BRCA1, 61 BRCA2); participants' mean age at entry was 43.3 years. Seventeen cancers were later diagnosed: 4 ductal carcinoma in situ (DCIS) and 13 early-stage invasive breast cancers. Fifteen cancers occurred in mutation carriers (11 BRCA1, 3 BRCA2, 1 CDH1). Median size of the invasive cancers was 0.61 cm. No patients had lymph node metastasis at time of diagnosis, and no interval invasive cancers occurred. The sensitivity of biannual MRI alone was 88.2% and annual MG plus biannual MRI was 94.1%. The cancer detection rate of biannual MRI alone was 0.7% per 100 screening episodes, which is similar to the cancer detection rate of 0.7% per 100 screening episodes for annual MG plus biannual MRI. The number of recalls and biopsies needed to detect one cancer by biannual MRI were 2.8 and 1.7 in BRCA1 carriers, 12.0 and 8.0 in BRCA2 carriers, and 11.7 and 5.0 in non-BRCA1/2 carriers, respectively. CONCLUSIONS: Biannual MRI performed well for early detection of invasive breast cancer in genomically stratified high-risk women. No benefit was associated with annual MG screening plus biannual MRI screening.See related commentary by Kuhl and Schrading, p. 1693.

2.
Front Oncol ; 8: 156, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29872641

RESUMO

Background: Several (neo)adjuvant treatments for patients with HER2-positive breast cancer have been compared in different randomized clinical trials. Since it is not feasible to conduct adequate pairwise comparative trials of all these therapeutic options, network meta-analysis offers an opportunity for more detailed inference for evidence-based therapy. Methods: Phase II/III randomized clinical trials comparing two or more different (neo)adjuvant treatments for HER2-positive breast cancer patients were included. Relative treatment effects were pooled in two separate network meta-analyses for overall survival (OS) and disease-free survival (DFS). Results: 17 clinical trials met our eligibility criteria. Two different networks of trials were created based on the availability of the outcomes: OS network (15 trials: 37,837 patients); and DFS network (17 trials: 40,992 patients). Two studies-the ExteNET and the NeoSphere trials-were included only in this DFS network because OS data have not yet been reported. The concept of the dual anti-HER2 blockade proved to be the best option in terms of OS and DFS. Chemotherapy (CT) plus trastuzumab (T) and lapatinib (L) and CT + T + Pertuzumab (P) are probably the best treatment options in terms of OS, with 62.47% and 22.06%, respectively. In the DFS network, CT + T + Neratinib (N) was the best treatment option with 50.55%, followed by CT + T + P (26.59%) and CT + T + L (20.62%). Conclusion: This network meta-analysis suggests that dual anti-HER2 blockade with trastuzumab plus either lapatinib or pertuzumab are probably the best treatment options in the (neo)adjuvant setting for HER2-positive breast cancer patients in terms of OS gain. Mature OS results are still expected for the Aphinity trial and for the sequential use of trastuzumab followed by neratinib, the treatment that showed the best performance in terms of DFS in our analysis.

3.
Bioinformatics ; 33(18): 2873-2881, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28505251

RESUMO

Motivation: Next generation sequencing technologies have enabled the study of the human microbiome through direct sequencing of microbial DNA, resulting in an enormous amount of microbiome sequencing data. One unique characteristic of microbiome data is the phylogenetic tree that relates all the bacterial species. Closely related bacterial species have a tendency to exhibit a similar relationship with the environment or disease. Thus, incorporating the phylogenetic tree information can potentially improve the detection power for microbiome-wide association studies, where hundreds or thousands of tests are conducted simultaneously to identify bacterial species associated with a phenotype of interest. Despite much progress in multiple testing procedures such as false discovery rate (FDR) control, methods that take into account the phylogenetic tree are largely limited. Results: We propose a new FDR control procedure that incorporates the prior structure information and apply it to microbiome data. The proposed procedure is based on a hierarchical model, where a structure-based prior distribution is designed to utilize the phylogenetic tree. By borrowing information from neighboring bacterial species, we are able to improve the statistical power of detecting associated bacterial species while controlling the FDR at desired levels. When the phylogenetic tree is mis-specified or non-informative, our procedure achieves a similar power as traditional procedures that do not take into account the tree structure. We demonstrate the performance of our method through extensive simulations and real microbiome datasets. We identified far more alcohol-drinking associated bacterial species than traditional methods. Availability and implementation: R package StructFDR is available from CRAN. Contact: chen.jun2@mayo.edu. Supplementary information: Supplementary data are available at Bioinformatics online.


Assuntos
Bactérias/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Microbiota/genética , Filogenia , Software , Genômica/métodos , Humanos , Polimorfismo Genético , Análise de Sequência de DNA/métodos
4.
Clin Genitourin Cancer ; 14(6): 511-517, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27150640

RESUMO

BACKGROUND: Level 1 evidence has demonstrated increased overall survival with cisplatin-based neoadjuvant chemotherapy for patients with muscle-invasive urothelial cancer. Usage remains low, however, in part because neoadjuvant chemotherapy will not be effective for every patient. To identify the patients most likely to benefit, we evaluated germline pharmacogenomic markers for association with neoadjuvant chemotherapy sensitivity in 2 large cohorts of patients with urothelial cancer. PATIENTS AND METHODS: Patients receiving neoadjuvant cisplatin-based chemotherapy for muscle-invasive urothelial cancer were eligible. Nine germline single nucleotide polymorphisms (SNPs) potentially conferring platinum sensitivity were tested for an association with a complete pathologic response to neoadjuvant chemotherapy (pT0) or elimination of muscle-invasive cancer (

Assuntos
Antineoplásicos/administração & dosagem , Carcinoma de Células de Transição/tratamento farmacológico , Cisplatino/administração & dosagem , Mutação em Linhagem Germinativa , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/farmacologia , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/patologia , Cisplatino/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Variantes Farmacogenômicos , Análise de Sobrevida , Resultado do Tratamento
5.
Biom J ; 58(4): 935-43, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26890370

RESUMO

In clinical studies, it is often of interest to see the diagnostic agreement among clinicians on certain symptoms. Previous work has focused on the agreement between two clinicians under two different conditions or the agreement among multiple clinicians under one condition. Few have discussed the agreement study with a design where multiple clinicians examine the same group of patients under two different conditions. In this paper, we use the intraclass kappa statistic for assessing nominal scale agreement with such a design. We derive an explicit variance formula for the difference of correlated kappa statistics and conduct hypothesis testing for the equality of kappa statistics. Simulation studies show that the method performs well with realistic sample sizes and may be superior to a method that did not take into account the measurement dependence structure. The practical utility of the method is illustrated on data from an eosinophilic esophagitis (EoE) study.


Assuntos
Biometria/métodos , Técnicas e Procedimentos Diagnósticos/normas , Modelos Estatísticos , Simulação por Computador , Humanos , Reprodutibilidade dos Testes , Projetos de Pesquisa , Tamanho da Amostra
6.
J Am Stat Assoc ; 110(511): 1187-1196, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26576066

RESUMO

Regression analysis of censored failure observations via the proportional hazards model permits time-varying covariates which are observed at death times. In practice, such longitudinal covariates are typically sparse and only measured at infrequent and irregularly spaced follow-up times. Full likelihood analyses of joint models for longitudinal and survival data impose stringent modelling assumptions which are difficult to verify in practice and which are complicated both inferentially and computationally. In this article, a simple kernel weighted score function is proposed with minimal assumptions. Two scenarios are considered: half kernel estimation in which observation ceases at the time of the event and full kernel estimation for data where observation may continue after the event, as with recurrent events data. It is established that these estimators are consistent and asymptotically normal. However, they converge at rates which are slower than the parametric rates which may be achieved with fully observed covariates, with the full kernel method achieving an optimal convergence rate which is superior to that of the half kernel method. Simulation results demonstrate that the large sample approximations are adequate for practical use and may yield improved performance relative to last value carried forward approach and joint modelling method. The analysis of the data from a cardiac arrest study demonstrates the utility of the proposed methods.

7.
J R Stat Soc Series B Stat Methodol ; 77(4): 755-776, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26568699

RESUMO

We consider estimation of regression models for sparse asynchronous longitudinal observations, where time-dependent responses and covariates are observed intermittently within subjects. Unlike with synchronous data, where the response and covariates are observed at the same time point, with asynchronous data, the observation times are mismatched. Simple kernel-weighted estimating equations are proposed for generalized linear models with either time invariant or time-dependent coefficients under smoothness assumptions for the covariate processes which are similar to those for synchronous data. For models with either time invariant or time-dependent coefficients, the estimators are consistent and asymptotically normal but converge at slower rates than those achieved with synchronous data. Simulation studies evidence that the methods perform well with realistic sample sizes and may be superior to a naive application of methods for synchronous data based on an ad hoc last value carried forward approach. The practical utility of the methods is illustrated on data from a study on human immunodeficiency virus.

8.
Parkinsonism Relat Disord ; 21(8): 877-81, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26037459

RESUMO

INTRODUCTION: The etiology of Parkinson's disease (PD) remains unclear. The aim of this study was to examine the association between common pathogenic infections and PD. METHODS: Antibody titers to common infectious pathogens including cytomegalovirus (CMV), Epstein Barr virus (EBV),herpes simplex virus type-1 (HSV-1), Borrelia burgdorferi (B. burgdorferi), Chlamydophila pneumoniae (C. pneumoniae) and Helicobacter pylori (H. pylori) were measured by ELISA in serum of 131 PD patients and 141 normal controls. Infectious burden (IB) was defined as a composite serologic measure of exposure to these common pathogens. RESULTS: Seropositivities toward zero-two, three-four and five-six of these pathogens were found in 11%, 74% and 15% of normal controls while in 4%, 61% and 35% of PD patients, respectively. IB, bacterial burden and viral burden were independently associated with PD. Schwab and England (S&E) scores were negatively correlated with IB in patients with PD. Serum α-synuclein protein levels and inflammatory cytokines (interleukin-1ß and interleukin-6) in individuals with higher IB were also significantly higher. CONCLUSIONS: IB consisting of CMV, EBV, HSV-1, B. burgdorferi, C. pneumoniae and H. pylori is associated with PD. This study supports the role of infection in the etiology of PD.


Assuntos
Anticorpos Antibacterianos/sangue , Anticorpos Antivirais/sangue , Bactérias Gram-Negativas/imunologia , Herpesviridae/imunologia , Interleucina-1beta/sangue , Interleucina-6/sangue , Doença de Parkinson/sangue , alfa-Sinucleína/sangue , Idoso , Borrelia burgdorferi/imunologia , Estudos de Casos e Controles , Chlamydophila pneumoniae/imunologia , Citomegalovirus/imunologia , Feminino , Helicobacter pylori/imunologia , Herpesvirus Humano 1/imunologia , Herpesvirus Humano 4/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
9.
Neurotox Res ; 27(3): 292-9, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25612546

RESUMO

Mounting evidence suggests that ischemic stroke (IS) is associated with Alzheimer's disease (AD). IS and vascular risk factors increase the risk for AD. However, whether AD pathologies exist in IS and the effects of these pathologies on stroke remain unknown. In the present study, we aimed to investigate the alterations of serum Aß after acute IS (AIS), and its correlations with the neurological deficits, infarction volume, and site after stroke. AIS patients (n = 35) were recruited within 24 h of symptom onset. Age- and gender-matched AD patients (n = 48) and cognitively normal controls (NC, n = 37) were also enrolled. Serum Aß40 and Aß42 and the National Institute of Health Stroke Scale Score (NIHSS) were measured on day 1, 3, and 7 after stroke onset. We found that serum Aß40 and Aß42 levels were increased at day 1 and reached peak levels at day 3, and decreased to pre-stroke levels at day 7. Serum Aß40 levels at day 1 were correlated with the NIHSS scores and infarction volume of AIS patients. Serum Aß42 levels at day 1 were significantly higher in IS patients with dominant gray matter infarction. Serum Aß40 levels at day 1 were predictive for NIHSS at day 7. Our results indicate that AIS can induce the generation of Aß in the brain, which may in turn be involved in the pathogenesis of neurological deficits after stroke. Serum Aß might be predictive for the short-term neurological deficits after AIS.


Assuntos
Peptídeos beta-Amiloides/sangue , Isquemia Encefálica/sangue , Isquemia Encefálica/psicologia , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/psicologia , Doença Aguda , Adulto , Idoso , Encéfalo/patologia , Isquemia Encefálica/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Acidente Vascular Cerebral/complicações
10.
Anticancer Drugs ; 26(3): 343-9, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25486599

RESUMO

Head and neck cancer patients undergoing chemoradiation experience considerable toxicities including acute kidney injury (AKI). However, it remains unclear what factors predispose patients to renal toxicity during treatment. Here, we assessed the predictors and outcomes of patients experiencing AKI during chemoradiation. We carried out a retrospective cohort study to assess the maximum changes in serum creatinine (Cr) in 173 patients with stage III-IV head and neck cancer treated with chemoradiation between 1999 and 2012. We defined AKI as Cr increases 26.5 µmol/l or more over the pretreatment baseline. AKI was associated with angiotensin-converting enzyme inhibitor (ACEI) use (33.0 vs. 11.0%; P=0.0004), but no other medications or comorbidities. On multivariate analysis, ACEI use, weight loss 10% or more of body weight, and performance status 70 or more predicted for Cr increments 26.5 µmol/l or more, whereas only ACEI use predicted for Cr increments of 44.2 µmol/l or greater. Furthermore, on multivariate analysis, AKI predicted for more interventions during radiotherapy including intravenous fluid use (P=0.0005) and hospitalizations (P=0.007), as well as long-term renal dysfunction (P<0.0001). Renal toxicity was not associated with worse locoregional control, progression-free survival, or overall survival. Renal toxicity during chemoradiation was associated with ACEI use alone or coupled with weight loss 10% or more of body weight during therapy. Our results suggest that actively managing ACEI use and intravascular volume status during chemoradiation may avoid AKI, minimize subsequent interventions, and reduce the risk for long-term renal dysfunction.


Assuntos
Lesão Renal Aguda/etiologia , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Quimiorradioterapia/efeitos adversos , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Lesão Renal Aguda/induzido quimicamente , Idoso , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Estudos de Coortes , Creatinina/sangue , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Perda de Peso/efeitos dos fármacos , Perda de Peso/efeitos da radiação
11.
Artigo em Chinês | MEDLINE | ID: mdl-25257265

RESUMO

OBJECTIVE: To investigate the efficacy of surgery followed by adjuvant radiotherapy and the prognostic factors affecting the results of treatment in hypopharyngeal carcinoma. METHODS: A retrospective review of 149 patients with hypopharyngeal carcinoma that received surgical treatment from Jun 2003 to Jun 2010 was accomplished. In the 149 patients, the site of origin were pyriform sinus (n = 121), posterior pharyngeal wall (n = 21) and postcricoid (n = 7). According to UICC 2002 criteria, there were 3 in stage I, 15 in stage II, 29 in stage III and 102 in stage IV. Surgical methods for primary tumor were: pyriform sinus resection or posterior pharyngeal wall resection in 22 cases, partial pharyngectomy and partial laryngectomy in 29 cases, partial pharyngectomy and total laryngectomy in 67 cases, total pharyngectomy and total laryngectomy in 16 cases, total pharyngolaryngectomy and partial esophagus resection in 12 cases, and total esophagus resection in 3 cases. All the patients received elective and/or radical neck dissection. Unilateral or bilateral thyroid lobectomy was performed in 98 cases. Eighty-seven patients received intensity modulation radiated therapy (IMRT) postoperatively in the cancer center of Provincial Hospital Affiliated to Shandong University. Individualized adjustment of the radiation field was made according to the surgical condition. Forty-nine cases received radiotherapy in other hospitals (dose 50-70 Gy). Laryngeal function was restored in 51 patients (34.2%). The risk clinicopathological factors of survival and the causes of death were analyzed. RESULTS: The survival rate was calculated with Kaplan-Meier method. The overall 3- and 5- year survival rates were 47.7% and 38.7%, respectively. There were no significant differences in 3-year survival between T1-2 and T3-4 groups, N0 and N+ groups, stage I-II and III-IV groups, laryngeal function preserved and unpreserved groups. The overall 3 years survival rate of patients received surgery and adjuvant radiotherapy was higher than those just received surgery alone (χ² = 6.851, P < 0.05). The 3-year survival rate in patients treated in comprehensive treatment group has showed a good trend, although still no statistical significance (χ² = 0.176, P > 0.05). The cause of death in 86 patients, including regional lymph nodes recurrence in 25 cases (29.1%). Of them, one was stoma recurrence and 9 were retropharyngeal lymph nodes metastasis; distant metastasis in 19 cases (22.1%); local recurrence in 13 cases, local or regional recurrence with distant metastasis in 8 cases (9.3%), and second primary cancer in 6 cases (7.0%). CONCLUSIONS: The overall prognosis of hypopharyngeal carcinoma was poor and dismal. In accordance with specific conditions of surgery, active adjustment of the personalized protocol of IMRT was the key of improving the efficacy of hypopharyngeal carcinoma.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias Hipofaríngeas/diagnóstico , Terapia Combinada , Humanos , Laringectomia , Laringe , Laringe Artificial , Linfonodos , Esvaziamento Cervical , Recidiva Local de Neoplasia , Segunda Neoplasia Primária , Faringectomia , Faringe , Radioterapia Adjuvante , Radioterapia de Intensidade Modulada , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Taxa de Sobrevida
12.
Artigo em Chinês | MEDLINE | ID: mdl-25257269

RESUMO

OBJECTIVE: To investigate the necessity and feasibility of planned dissection of the retropharyngeal lymph nodes (RPLN) in advanced hypopharyngeal cancer. METHODS: Between February 2011 and December 2012, 54 patients with advanced hypopharyngeal cancer accepted planned dissection of the RPLN during primary surgery. There were 45 cases of pyriform sinus carcinoma, 5 cases of posterior pharyngeal wall carcinoma, and 4 cases of postcricoid carcinoma. All patients underwent surgery and postoperative adjuvant radiotherapy, meanwhile bilateral neck dissection and RPLN dissection were performed. All patients received preoperative CT scanning (with contrast). The results of the radiographic assessment were compared with the postoperative pathologic findings respectively. RESULTS: RPLN were confirmed positive by pathology in 13 cases, and negative in another 43 cases. For the entire treatment group, metastasis to the RPLN was confirmed hispathologically in 12 patients (22.2%). Eight patients were pyriform sinus carcinoma, 4 were posterior pharyngeal wall carcinoma. Among them, seven patients were diagnosed as RPLN metastasis by CT imaging and another 5 patients were not confirmed. The overall accuracy for the radiologist's interpretation was 79.6%, the sensitivity was 58.3%, and the specificity was found to be 85.7%. Eleven patients were N2-3 and 6 patients were N2c. No RPLN metastasis or recurrence was found during more than one year follow-up period. CONCLUSIONS: It is not rare for the RPLN metastasis in patients with advanced hypopharyngeal carcinoma. CT imaging is not effective in determining the early presence of RPLN metastasis. The planned dissection of the RPLN is highly recommended during the initial surgery of hypopharyngeal cancer, especially in posterior pharyngeal wall carcinoma, T3-4 pyriform sinus carcinoma and staged N2-3 cases.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias Hipofaríngeas/cirurgia , Humanos , Linfonodos/cirurgia , Metástase Linfática , Pescoço , Esvaziamento Cervical , Recidiva Local de Neoplasia , Neoplasias Faríngeas , Radioterapia Adjuvante , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Tomografia Computadorizada por Raios X
13.
J Infect Dis ; 210(7): 1012-8, 2014 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-24740631

RESUMO

Staphyococcus aureus frequently causes recurrent skin and soft-tissue infection (SSTI). In the pediatric population, elevated serum antibody targeting S. aureus α-toxin is correlated with a reduced incidence of recurrent SSTI. Using a novel model of recurrent SSTI, we demonstrated that expression of α-toxin during primary infection increases the severity of recurrent disease. Antagonism of α-toxin by either a dominant-negative toxin mutant or a small molecule inhibitor of the toxin receptor ADAM10 during primary infection reduces reinfection abscess severity. Early neutralization of α-toxin activity during S. aureus SSTI therefore offers a new therapeutic strategy to mitigate primary and recurrent disease.


Assuntos
Toxinas Bacterianas/toxicidade , Proteínas Hemolisinas/toxicidade , Infecções dos Tecidos Moles/patologia , Infecções Cutâneas Estafilocócicas/patologia , Staphylococcus aureus/fisiologia , Animais , Toxinas Bacterianas/antagonistas & inibidores , Toxinas Bacterianas/metabolismo , Proteínas Hemolisinas/antagonistas & inibidores , Proteínas Hemolisinas/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Recidiva , Infecções dos Tecidos Moles/tratamento farmacológico , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/metabolismo
14.
Leuk Lymphoma ; 55(12): 2866-73, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24564572

RESUMO

Abstract We examined clofarabine pharmacokinetics and association with renal toxicity in 62 patients participating in a phase I-II study of clofarabine-melphalan-alemtuzumab conditioning for hematopoietic stem cell transplant (HSCT). Pharmacokinetic parameters, including clofarabine area under the concentration-time curve (AUC), maximum concentration and clearance, were measured, and patients were monitored for renal injury. All patients had normal pretreatment creatinine values, but over half (55%) experienced acute kidney injury (AKI) after clofarabine administration. Age was the strongest predictor of AKI, with older patients at greater risk (p = 0.002). Clofarabine AUC was higher in patients who developed AKI, and patients with the highest dose-normalized AUCs experienced the most severe grades of AKI (p = 0.01). Lower baseline renal function, even when normal, was associated with lower clofarabine clearance (p = 0.008). These data suggest that renal-adjustment of clofarabine dosing should be considered for older and at-risk patients even when renal function is ostensibly normal.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Nucleotídeos de Adenina/efeitos adversos , Antimetabólitos Antineoplásicos/efeitos adversos , Arabinonucleosídeos/efeitos adversos , Transplante de Células-Tronco Hematopoéticas , Condicionamento Pré-Transplante/efeitos adversos , Lesão Renal Aguda/diagnóstico , Nucleotídeos de Adenina/administração & dosagem , Nucleotídeos de Adenina/farmacocinética , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/farmacocinética , Arabinonucleosídeos/administração & dosagem , Arabinonucleosídeos/farmacocinética , Área Sob a Curva , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Clofarabina , Feminino , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Índice de Gravidade de Doença , Transplante Homólogo
15.
Artigo em Chinês | MEDLINE | ID: mdl-25598364

RESUMO

OBJECTIVE: To study the feasibility and therapeutic effect of recurrent laryngeal nerve (RLN) decompression in the treatment of bilateral paralyzed RLN after thyroid surgery. METHODS: From March 2005 to June 2013, 15 cases of bilateral RLN paralyses occurring within 3 months after thyroid surgery were treated with RLN decompression. Bilateral RLN paralyses were caused by revised thyroid surgery in 8 cases and by primary thyroid surgery in 7 cases. RESULTS: RLN injuries were found in 15 cases/22 side, including RLN-cut in 9 sides and RLN-ligated in 13 sides. RLN decompression was performed in the 10 cases/13 sides of ligated RLN. Vocal cord mobility was detected through electrolaryngoscope for evaluating the postoperative functional recovery of decompressed RLN.Of 8 patients with bilateral RLN paralyses due to the ligation of RLN after previous revised thyroid surgeries, functional adduction and abduction of the vocal cord was recovered completely in 4 patients and recovered basically with a slight weak abduction in one patient after RLN decompression, and the 5 patients were decannulated in 1-4 months postoperatively. For 7 patients with bilateral RLN paralyses resulted from previous primary surgeries, unilateral or bilateral RLN decompress was performed in 2 cases and in 3 cases respectively. The mobility of the paralyzed vocal cord restored in 1-6 months after RLN decompression, besides one case with relative deficient abduction and one case with slight limited abduction and adduction, and the 5 patients were decannulated successfully. CONCLUSION: Exploration surgery could be performed as soon as possible in patients with bilateral RLN paralyses and RLN decompress is effective for the restoration of the function of the nerve.


Assuntos
Traumatismos do Nervo Laríngeo Recorrente/etiologia , Nervo Laríngeo Recorrente , Glândula Tireoide/cirurgia , Tireoidectomia , Descompressão Cirúrgica , Humanos , Período Pós-Operatório , Traumatismos do Nervo Laríngeo Recorrente/diagnóstico , Paralisia das Pregas Vocais , Prega Vocal
16.
Cancer Inform ; 13(Suppl 4): 91-3, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25733794
17.
Cancer ; 120(2): 244-52, 2014 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-24122486

RESUMO

BACKGROUND: Although black patients experience worse outcomes after treatment for squamous cell carcinoma of the head and neck (HNSCC), these conclusions were based on populations in which blacks comprised a minority of patients. The objective of the current study was to determine the impact of race on outcomes in patients with HNSCC who received radiotherapy at an institution in which blacks comprised the majority of patients. METHODS: In this retrospective cohort study, the authors reviewed 366 black patients and 236 white patients who had nonmetastatic HNSCC for which they received radiotherapy between 1990 and 2012. The primary study outcome measures were locoregional control, freedom from distant metastasis, progression-free survival, and overall survival. RESULTS: The median follow-up was 18.3 months for all patients. The 2-year locoregional control rate was 71.9% for black patients compared with 64.2% for white patients (hazard ratio, 0.72; P=.03). There was no difference between blacks and whites regarding 2-year freedom from distant metastasis, progression-free survival, or overall survival. Among the patients who had stage III through IVB disease, blacks and whites had similar outcomes. On multivariate analysis, race was not statistically significant for locoregional control, freedom from distant metastasis, progression-free survival, or overall survival. Despite these similar outcomes, black patients had worse socioeconomic factors and increased comorbidities but had similar treatment compliance compared with white patients. CONCLUSIONS: With more adverse prognostic factors, black patients experienced oncologic outcomes similar to the outcomes of white patients after receiving radiotherapy for HNSCC. The current data suggest that centers that treat large percentages of minority patients who receive radiotherapy for HNSCCs may overcome existing health care disparities through improved treatment compliance.


Assuntos
Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeça e Pescoço/radioterapia , Afro-Americanos , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Dermatite/etiologia , Intervalo Livre de Doença , Grupo com Ancestrais do Continente Europeu , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Radioterapia/efeitos adversos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Resultado do Tratamento
18.
PLoS One ; 8(11): e80691, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24260455

RESUMO

BACKGROUND: We utilized data from the Health Effects of Arsenic Longitudinal Study (HEALS) in Araihazar, Bangladesh, to evaluate the association of steamed rice consumption with urinary total arsenic concentration and arsenical skin lesions in the overall study cohort (N=18,470) and in a subset with available urinary arsenic metabolite data (N=4,517). METHODS: General linear models with standardized beta coefficients were used to estimate associations between steamed rice consumption and urinary total arsenic concentration and urinary arsenic metabolites. Logistic regression models were used to estimate prevalence odds ratios (ORs) and their 95% confidence intervals (CIs) for the associations between rice intake and prevalent skin lesions at baseline. Discrete time hazard models were used to estimate discrete time (HRs) ratios and their 95% CIs for the associations between rice intake and incident skin lesions. RESULTS: Steamed rice consumption was positively associated with creatinine-adjusted urinary total arsenic (ß=0.041, 95% CI: 0.032-0.051) and urinary total arsenic with statistical adjustment for creatinine in the model (ß=0.043, 95% CI: 0.032-0.053). Additionally, we observed a significant trend in skin lesion prevalence (P-trend=0.007) and a moderate trend in skin lesion incidence (P-trend=0.07) associated with increased intake of steamed rice. CONCLUSIONS: This study suggests that rice intake may be a source of arsenic exposure beyond drinking water.


Assuntos
Arsênico/toxicidade , Arsênico/urina , Exposição Ambiental , Contaminação de Alimentos , Oryza/química , Adolescente , Adulto , Bangladesh/epidemiologia , Água Potável/análise , Água Potável/química , Feminino , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Dermatopatias/epidemiologia , Dermatopatias/etiologia , Adulto Jovem
19.
Surgery ; 154(6): 1436-46; discussion 1446-7, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24075674

RESUMO

BACKGROUND: Although recurrence and death can occur in patients with papillary thyroid cancer (PTC) several years after being diagnosed, the necessary duration of follow-up for these patients remains unclear. METHODS: This was a single-institution, retrospective review of 269 patients with PTC. Cox proportional hazards model and Kaplan-Meier curves were used to identify risk factors for recurrence and death. Risk predictors included age, sex, radiation exposure history, extent of operation, radioactive iodine treatment, follicular variant of PTC (FVPTC), extrathyroidal invasion, multifocality, TNM status, and stage. RESULTS: Median follow-up was 27 years. Of 269 patients, 180 (66%) were female, and 196 (73%) were ≤45 years of age. Recurrence and cancer-specific death rates were 28% and 9%, respectively. Time to recurrence (±SD) was 8.1 (± 8.3) years and to cancer-specific death was 9.0 (± 11.0) years; however, 11% of recurrences and 17% of deaths occurred after 20 years. Risk factors for recurrence were older age, FVPTC, T4 tumors, cervical lymph node involvement, metastases, and stage ≥ 4a. Predictors of death from PTC were older age, metastases, and stage ≥ 3. CONCLUSION: Both recurrences and death from PTC can occur more than 30 years after being treated, thus lifelong follow-up of patients with PTC is necessary.


Assuntos
Carcinoma Papilar/mortalidade , Carcinoma/mortalidade , Neoplasias da Glândula Tireoide/mortalidade , Adulto , Idoso , Carcinoma/patologia , Carcinoma/terapia , Carcinoma Papilar/patologia , Carcinoma Papilar/terapia , Chicago/epidemiologia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Fatores de Risco , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/terapia , Fatores de Tempo
20.
Neurosci Lett ; 550: 55-9, 2013 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-23831349

RESUMO

Alzheimer's disease (AD) is characterized by the degeneration of basal forebrain cholinergic neurons, whose survival and function are affected by neurotrophins and their receptors. The impaired signaling pathway of brain-derived neurotrophic factor/tropomyosin-related kinase B (BDNF/TrkB) is considered to play an important role in AD pathogenesis. To explore the association of polymorphisms within the NTRK2 gene (encoding TrkB) and sporadic AD (sAD), a case-control study was conducted in a Chinese Han cohort including 216 sAD patients and 244 control participants. Five single nucleotide polymorphisms (SNPs), with four of them within the promoter region and one in intron, were selected and genotyped with a polymerase chain reaction-ligase detection reaction (PCR-LDR) method. No association was revealed between these SNPs or the haplotypes containing four promoter SNPs and the risk of sAD. The results of this study indicate that polymorphisms in the selected regions of the NTRK2 gene are unlikely to confer the susceptibility of sAD in the Chinese Han population.


Assuntos
Doença de Alzheimer/genética , Grupo com Ancestrais do Continente Asiático/genética , Receptor trkB/genética , Idoso , Idoso de 80 Anos ou mais , Alelos , Doença de Alzheimer/etnologia , Estudos de Casos e Controles , China , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas
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