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1.
EMBO Mol Med ; 11(8): e10316, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31313878

RESUMO

Hematopoiesis, or the process of blood cell production, is a paradigm of multi-lineage cellular differentiation that has been extensively studied, yet in many aspects remains incompletely understood. Nearly all clinically measured hematopoietic traits exhibit extensive variation and are highly heritable, underscoring the importance of genetic variation in these processes. This review explores how human genetics have illuminated our understanding of hematopoiesis in health and disease. The study of rare mutations in blood and immune disorders has elucidated novel roles for regulators of hematopoiesis and uncovered numerous important molecular pathways, as seen through examples such as Diamond-Blackfan anemia and the GATA2 deficiency syndromes. Additionally, population studies of common genetic variation have revealed mechanisms by which human hematopoiesis can be modulated. We discuss advances in functionally characterizing common variants associated with blood cell traits and discuss therapeutic insights, such as the discovery of BCL11A as a modulator of fetal hemoglobin expression. Finally, as genetic techniques continue to evolve, we discuss the prospects, challenges, and unanswered questions that lie ahead in this burgeoning field.

2.
Pediatr Blood Cancer ; 66(9): e27874, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31207059

RESUMO

Growth factor-independent 1B (GFI1B) variants are a rare cause of thrombocytopenia. We report on a male child who was initially diagnosed with immune thrombocytopenia. However, subtle clinical signs led to suspicion of a genetic cause of thrombocytopenia. Gene panel sequencing revealed a rare variant in GFI1B (C168F), which has recently been reported in several families with thrombocytopenia. We demonstrate that this variant significantly alters platelet parameters in population studies. This case highlights how diagnoses of exclusion, such as immune thrombocytopenia, can be confounded by genetic variation. Our understanding of blood disorders will undoubtedly evolve from an increased knowledge of human genetic variation.

4.
Am J Hum Genet ; 2018 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-30503522

RESUMO

Diamond-Blackfan anemia (DBA) is a rare bone marrow failure disorder that affects 7 out of 1,000,000 live births and has been associated with mutations in components of the ribosome. In order to characterize the genetic landscape of this heterogeneous disorder, we recruited a cohort of 472 individuals with a clinical diagnosis of DBA and performed whole-exome sequencing (WES). We identified relevant rare and predicted damaging mutations for 78% of individuals. The majority of mutations were singletons, absent from population databases, predicted to cause loss of function, and located in 1 of 19 previously reported ribosomal protein (RP)-encoding genes. Using exon coverage estimates, we identified and validated 31 deletions in RP genes. We also observed an enrichment for extended splice site mutations and validated their diverse effects using RNA sequencing in cell lines obtained from individuals with DBA. Leveraging the size of our cohort, we observed robust genotype-phenotype associations with congenital abnormalities and treatment outcomes. We further identified rare mutations in seven previously unreported RP genes that may cause DBA, as well as several distinct disorders that appear to phenocopy DBA, including nine individuals with biallelic CECR1 mutations that result in deficiency of ADA2. However, no new genes were identified at exome-wide significance, suggesting that there are no unidentified genes containing mutations readily identified by WES that explain >5% of DBA-affected case subjects. Overall, this report should inform not only clinical practice for DBA-affected individuals, but also the design and analysis of rare variant studies for heterogeneous Mendelian disorders.

5.
J Cell Biol ; 217(9): 3301-3311, 2018 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-29980624

RESUMO

We developed a general approach for investigation of how cellular processes become adapted for specific cell types during differentiation. Previous studies reported substantial differences in the morphology and dynamics of clathrin-mediated endocytosis (CME) sites. However, associating specific CME properties with distinct differentiated cell types and determining how these properties are developmentally specified during differentiation have been elusive. Using genome-edited human embryonic stem cells, and isogenic fibroblasts and neuronal progenitor cells derived from them, we established by live-cell imaging and platinum replica transmission electron microscopy that CME site dynamics and ultrastructure on the plasma membrane are precisely reprogrammed during differentiation. Expression levels for the endocytic adaptor protein AP2µ2 were found to underlie dramatic changes in CME dynamics and structure. Additionally, CME dependency on actin assembly and phosphoinositide-3 kinase activity are distinct for each cell type. Collectively, our results demonstrate that key CME properties are reprogrammed during differentiation at least in part through AP2µ2 expression regulation.

6.
J Cardiothorac Vasc Anesth ; 32(6): 2654-2661, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29754733

RESUMO

OBJECTIVE: The authors investigated the effect of preoperative thoracic epidural (PreTE) catheter placement versus not placing a preoperative thoracic epidural catheter (NoPreTE) on the duration of postoperative ventilation time, time to become coherent (measured as time to become Confusion Assessment Method-intensive care unit [ICU] negative), opioid consumption, ICU length of stay (LOS), and hospital LOS. DESIGN: Retrospective cohort design. SETTING: Single institution, university hospital. PARTICIPANTS: Patients undergoing lung transplantation. COMPARISON GROUPS: PreTE group was defined as patients who received a thoracic epidural preoperatively. NoPreTE group was defined as patients who either received a thoracic epidural postoperatively or who did not receive a thoracic epidural postoperatively. MEASUREMENTS AND MAIN RESULTS: Fifty-six patients for the PreTE and 99 for NoPreTE groups were included in the study. After a excluding patients with postoperative ventilation times greater than 96 hours, preoperative thoracic epidural was associated with shorter time on the ventilator (19.1 hours v 30.6 hours; p < 0.001), time to become coherent (26.4 hours v 37.6 hours; p = 0.008), ICU LOS (6.4 days v 12.4 days; p = 0.018), and hospital LOS (15.9 days v 23.5 days; p = 0.04) compared to patients who did not receive a preoperative epidural. After controlling for single versus double lung transplantation and duration of cardiopulmonary bypass (CPB), differences in time to become coherent, ICU LOS, and hospital LOS became nonsignificant. Opioid consumption was significantly higher in those patients who did not receive a preoperative epidural. Despite a high rate of anticoagulation for CPB (89.5%), no neurologic complications or epidural hematomas were observed. CONCLUSION: For those lung transplant patients ventilated for less than 96 hours postoperatively, preoperative thoracic epidural placement is associated with shorter postoperative ventilator time and reduced opioid consumption. Time to become coherent postoperatively, ICU LOS, and hospital LOS also improved in this cohort, though the significance decreased after adjusting for possible confounders. A larger prospective study is necessary to confirm if timing of thoracic epidural placement alters time to become coherent postoperatively and ICU LOS.

7.
Ann Thorac Surg ; 104(1): 227-233, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28577842

RESUMO

BACKGROUND: Surgical repair or drainage is the standard treatment for benign esophageal perforation. The United States Food and Drug Administration has approved the use of esophageal stents for the management of malignant esophageal stricture or fistula, or both. We hypothesize that increasing enthusiasm and experience with esophageal stents has led to greater use of stents for the management of benign esophageal perforation. METHODS: We performed a retrospective cohort study (2007 to 2014) of patients with benign esophageal perforation using MarketScan (Thomson Reuters, New York, NY), a commercial claims database. Patients had 6 months of follow-up. Regression was used for risk-adjustment. RESULTS: Benign esophageal perforation was treated in 659 patients (mean age, 49 years; 41% women), comprising surgical repair in 449 (69%), surgical drainage in 110 (17%), and stent in 100 (15%). Stent use increased from 7% in 2007 to 30% in 2014 (p < 0.001 for trend). Over the same period, surgical repair decreased from 71% to 53% (p = 0.001 for trend), but surgical drainage did not change (p = 0.24). After adjustment for other factors that could vary over time, stent use increased by 28% per year (incidence rate ratio, 1.28; 95% confidence interval, 1.17 to 1.39). Changes in risk-adjusted deaths, discharges home, readmissions, or costs over the same period were not significant (all p > 0.05 for trend). CONCLUSIONS: The use of stents for the management of benign esophageal perforation has increased by over fourfold in just 8 years, but short-term outcomes have not changed over time for this population of patients. A national registry for off-label use of esophageal stents may clarify the indications for and risks and benefits of stenting benign esophageal perforations.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/métodos , Perfuração Esofágica/cirurgia , Esôfago/cirurgia , Stents/estatística & dados numéricos , Perfuração Esofágica/diagnóstico , Esofagoscopia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Estados Unidos
8.
J Heart Lung Transplant ; 36(4): 443-450, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27863861

RESUMO

BACKGROUND: Hospital readmissions are costly and have become a focus for quality improvement. We aimed to determine risk factors, rate, and outcomes of readmissions within the first year after lung transplantation and the potential impact on patient survival. METHODS: A retrospective cohort study of all lung transplant recipients ≥18 years old who had undergone initial transplantation (2004-2013) at a single center was conducted. Logistic regression was used to identify independent predictors of readmission for patients who survived hospitalization. Cox regression was used to explore the relationship between readmission and long-term risk of death, while adjusting for potential confounders for patients who survived the first year. RESULTS: During the study period, 412 patients met inclusion criteria for the readmission analysis. There were 276 patients (67%) readmitted within 1 year after lung transplantation for a total of 609 readmissions (average ± SD, 1.5 ± 2). Average length of readmission stay was 6 days ± 7, with 44% of readmissions lasting ≤3 days. Airway complications were found to be a significant risk factor for readmission (odds ratio, 4.18; 95% confidence interval, 1.78-9.54; p = 0.001). After adjustment, the overall risk of death was significantly higher with each readmission during the first year (hazard ratio, 1.22; 95% confidence interval, 1.13-1.31, p < 0.0001). CONCLUSIONS: Most patients who survive the first post-operative year experience at least 1 readmission, with patients who experience airway complications at particular risk. Patients discharged to inpatient rehabilitation were less likely to be readmitted. The cumulative burden of multiple readmissions is associated with worse long-term survival.


Assuntos
Pneumopatias/cirurgia , Transplante de Pulmão/efeitos adversos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Readmissão do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Modelos Logísticos , Pneumopatias/complicações , Pneumopatias/mortalidade , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo
9.
Hepatol Commun ; 1(8): 803-815, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-29404495

RESUMO

Iron overload causes the generation of reactive oxygen species that can lead to lasting damage to the liver and other organs. The goal of this study was to identify genes that modify the toxicity of iron overload. We studied the effect of iron overload on the hepatic transcriptional and metabolomic profile in mouse models using a dietary model of iron overload and a genetic model, the hemojuvelin knockout mouse. We then evaluated the correlation of nicotinamide N-methyltransferase (NNMT) expression with body iron stores in human patients and the effect of NNMT knockdown on gene expression and viability in primary mouse hepatocytes. We found that iron overload induced significant changes in the expression of genes and metabolites involved in glucose and nicotinamide metabolism and that NNMT, an enzyme that methylates nicotinamide and regulates hepatic glucose and cholesterol metabolism, is one of the most strongly down-regulated genes in the liver in both genetic and dietary iron overload. We found that hepatic NNMT expression is inversely correlated with serum ferritin levels and serum transferrin saturation in patients who are obese, suggesting that body iron stores regulate human liver NNMT expression. Furthermore, we demonstrated that adenoviral knockdown of NNMT in primary mouse hepatocytes exacerbates iron-induced hepatocyte toxicity and increases expression of transcriptional markers of oxidative and endoplasmic reticulum stress, while overexpression of NNMT partially reversed these effects. Conclusion: Iron overload alters glucose and nicotinamide transcriptional and metabolic pathways in mouse hepatocytes and decreases NNMT expression, while NNMT deficiency worsens the toxic effect of iron overload. For these reasons, NNMT may be a drug target for the prevention of iron-induced hepatotoxicity. (Hepatology Communications 2017;1:803-815).

11.
Blood Cells Mol Dis ; 60: 36-43, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27519943

RESUMO

Hepcidin, a peptide produced in the liver, decreases intestinal iron absorption and macrophage iron release by causing degradation of the iron exporter, ferroportin. Because its levels are inappropriately low in patients with iron overload syndromes, hepcidin is a potential drug target. We previously conducted a chemical screen that revealed ipriflavone, an orally available small molecule, as a potent inducer of hepcidin expression. To evaluate ipriflavone's effect on iron homeostasis, we placed groups of 5-week old wild type or thalassemia intermedia (Hbb(Th3+/-)) mice on a soy-free, iron-sufficient diet, AIN-93G containing 220mg iron and 0-750mgipriflavone/kg of food for 50days. Ipriflavone 500mg/kg significantly reduced liver iron stores and intestinal ferroportin expression in WT mice, while increasing the ratio of hepcidin transcript levels to liver iron stores. Ipriflavone supplementation in Hbb(Th3+/-) mice failed to alleviate iron overload and was associated with a milder reduction in intestinal ferroportin and a failure to alter the ratio of hepcidin transcript levels to liver iron stores or splenic expression of the hepcidin-regulatory hormone, erythroferrone. These data suggest that dietary supplementation with ipriflavone alone would not be sufficient to treat iron overload in thalassemia intermedia.


Assuntos
Suplementos Nutricionais , Sobrecarga de Ferro/tratamento farmacológico , Ferro/metabolismo , Isoflavonas/farmacologia , Fígado/metabolismo , Animais , Proteínas de Transporte de Cátions/efeitos dos fármacos , Hepcidinas/genética , Ferro/administração & dosagem , Sobrecarga de Ferro/prevenção & controle , Isoflavonas/uso terapêutico , Fígado/efeitos dos fármacos , Camundongos , RNA Mensageiro/efeitos dos fármacos , Falha de Tratamento , Talassemia beta/tratamento farmacológico
12.
Ann Thorac Surg ; 100(6): 2006-12, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26507425

RESUMO

BACKGROUND: Practice guidelines recommend routine use of pulmonary function tests (PFTs), computed tomography (CT), and positron emission tomography (PET) for the workup of resectable lung cancer patients. Little is known about the frequency of guideline concordance in routine practice. METHODS: A cohort study (2007 to 2013) of 15,951 lung cancer patients undergoing lobectomy or pneumonectomy was conducted with MarketScan, a claims database of individuals with employer-provided health insurance. Guideline concordance was defined by claims for PFT within 180 days of resection and for CT and PET within 90 days of resection. Generalized linear models were used to evaluate temporal trends, patient characteristics, and costs associated with guideline-concordant care. RESULTS: Overall, 61% of patients received guideline-concordant care, increasing from 57% in 2007 to 66% in 2013 (p < 0.001). Compared with patients who received guideline-discordant care, patients with guideline-concordant care more frequently underwent repeat testing (PFT: 21% versus 12%, p < 0.001; CT: 46% versus 22%, p < 0.001; PET: 2.3% versus 1.1%, p < 0.001). Health plan-adjusted mean total test-related costs were higher among guideline-concordant patients who underwent repeat testing than patients who did not ($4,304 versus $3,454, p < 0.001). CONCLUSIONS: Forty percent of lung cancer patients treated with surgical procedures did not receive recommended noninvasive cancer staging and physiologic assessment before resection. Guideline concordance was associated with repeat testing, and repeat testing was associated with higher costs. These findings support the need for quality improvement interventions that can increase guideline concordance while curbing potential excess use of diagnostic tests.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Diagnóstico por Imagem/normas , Fidelidade a Diretrizes , Neoplasias Pulmonares/diagnóstico , Estadiamento de Neoplasias/normas , Guias de Prática Clínica como Assunto/normas , Testes de Função Respiratória/normas , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/normas , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/normas
13.
J Thorac Dis ; 7(4): 576-84, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25973222

RESUMO

BACKGROUND: A prediction model for pathologic N2 (pN2) among lung cancer patients with a negative mediastinum by positron emission tomography (PET) was recently internally validated. Our study sought to determine the external validity of that model. METHODS: A cohort study [2005-2013] was performed of lung cancer patients with a negative mediastinum by PET. Previously published model coefficients were used to estimate the probability of pN2 based on tumor location and size, nodal enlargement by computed tomography (CT), maximum standardized uptake value (SUVmax) of the primary tumor, N1 disease by PET, and pretreatment histology. RESULTS: Among 239 patients, 18 had pN2 [7.5%, 95% confidence interval (CI): 4.5-12%]. Model discrimination was excellent (c-statistic 0.80, 95% CI: 0.75-0.85) and the model fit the data well (P=0.191). The accuracy of the model was as follows: sensitivity 100%, 95% CI: 81-100%; specificity 49%, 95% CI: 42-56%; positive predictive value (PPV) 14%, 95% CI: 8-21%, and negative predictive value (NPV) 100%, 95% CI: 97-100%. CI inspection revealed a significantly higher c-statistic in this external validation cohort compared to the internal validation cohort. The model's apparently poor specificity for patient selection is in fact significantly better than usual care (i.e., aggressive but allowable guideline concordant staging) and minimum guideline mandated selection criteria for invasive staging. CONCLUSIONS: A prediction model for pN2 is externally valid. The high NPV of this model may allow pulmonologists and thoracic surgeons to more comfortably minimize the number of invasive procedures performed among patients with a negative mediastinum by PET.

14.
Oncology (Williston Park) ; 29(3): 160-6, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25772453

RESUMO

Low-dose computed tomography (LDCT) screening decreases lung cancer mortality in high-risk individuals and has now been approved and adopted for lung cancer screening in the United States. As more LDCT lung cancer screening programs are implemented, more patients with early-stage lung cancer who could benefit from surgical intervention will be identified. Although lobectomy currently remains the standard of care for early-stage non-small-cell lung cancer (NSCLC), thoracic surgeons are increasingly adopting minimally invasive surgery via thoracoscopy as a viable-and perhaps even preferred-approach for select lung cancer resections. Video-assisted thoracic surgery (VATS) lobectomy has been associated with decreased perioperative morbidity, and similar rates of locoregional recurrence and cancer-free survival can be achieved compared with the standard open surgical procedure. However, as lung cancers are detected at earlier stages, the optimal extent of lung resection for long-term cure continues to be investigated. For patients with very small-sized lung tumors and indolent lesions, cancer-free survival may not necessarily be compromised by undergoing less invasive approaches that intentionally resect less lung tissue, such as sublobar resections (eg, segmentectomy and wedge resection). This review looks at the current data and guidelines for thoracoscopic resection of stage I NSCLC and discusses the potential for limited lung resection in patients with the disease.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Pneumonectomia/métodos , Cirurgia Torácica Vídeoassistida , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Intervalo Livre de Doença , Detecção Precoce de Câncer/métodos , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Pneumonectomia/efeitos adversos , Pneumonectomia/mortalidade , Valor Preditivo dos Testes , Fatores de Risco , Cirurgia Torácica Vídeoassistida/efeitos adversos , Cirurgia Torácica Vídeoassistida/mortalidade , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Carga Tumoral
15.
J Thorac Cardiovasc Surg ; 149(5): 1365-71; discussion 1371-3.e3, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25791948

RESUMO

OBJECTIVE: Failure to rescue is defined as death after an acute inpatient event and has been observed among hospitals that perform general, vascular, and cardiac surgery. This study aims to evaluate variation in complication and failure to rescue rates among hospitals that perform pulmonary resection for lung cancer. METHODS: By using the Society of Thoracic Surgeons General Thoracic Surgery Database, a retrospective, multicenter cohort study was performed of adult patients with lung cancer who underwent pulmonary resection. Hospitals participating in the Society of Thoracic Surgeons General Thoracic Surgery Database were ranked by their risk-adjusted, standardized mortality ratio (using random effects logistic regression) and grouped into quintiles. Complication and failure to rescue rates were evaluated across 5 groups (very low, low, medium, high, and very high mortality hospitals). RESULTS: Between 2009 and 2012, there were 30,000 patients cared for at 208 institutions participating in the Society of Thoracic Surgeons General Thoracic Surgery Database (median age, 68 years; 53% were women, 87% were white, 71% underwent lobectomy, 65% had stage I). Mortality rates varied over 4-fold across hospitals (3.2% vs 0.7%). Complication rates occurred more frequently at hospitals with higher mortality (42% vs 34%, P < .001). However, the magnitude of variation (22%) in complication rates dwarfed the 4-fold magnitude of variation in failure to rescue rates (6.8% vs 1.7%, P < .001) across hospitals. CONCLUSIONS: Variation in hospital mortality seems to be more strongly related to rescuing patients from complications than to the occurrence of complications. This observation is significant because it redirects quality improvement and health policy initiatives to more closely examine and support system-level changes in care delivery that facilitate early detection and treatment of complications.


Assuntos
Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Pneumonectomia/mortalidade , Complicações Pós-Operatórias/mortalidade , Idoso , Bases de Dados Factuais , Assistência à Saúde , Feminino , Mortalidade Hospitalar , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Pneumonectomia/efeitos adversos , Complicações Pós-Operatórias/terapia , Melhoria de Qualidade , Indicadores de Qualidade em Assistência à Saúde , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Falha de Tratamento , Estados Unidos/epidemiologia
16.
J Natl Compr Canc Netw ; 13(2): 166-70, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25691608

RESUMO

Surgery remains the primary therapy in the treatment of early-stage lung cancer. Traditionally, anatomic resection via open thoracotomy has been the conventional approach, but as experience with minimally invasive lung surgery has increased, video-assisted thoracoscopic surgical (VATS) lobectomy is being performed more commonly for treatment of lung cancer. Proponents of VATS have argued that thoracoscopic resection for lung cancer is not only safe but is also superior to the open approach. VATS enthusiasts even have proposed that this approach should be the standard of care and a metric for quality in lung cancer surgery. Such zeal for promoting a "preferred" technique, however, obscures focus from other time-proven, but perhaps less fashionable, factors that have a tremendous impact on quality and lung cancer outcomes, namely cancer staging and quality of cancer surgery. Rather than debate incisions, thoracic surgeons should advocate for specialty care and surgical quality that assures the best short- and long-term outcomes for patients, regardless of the surgical approach.


Assuntos
Neoplasias Pulmonares/cirurgia , Pneumonectomia , Cirurgia Torácica Vídeoassistida , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Pneumonectomia/métodos , Cirurgia Torácica Vídeoassistida/métodos , Resultado do Tratamento
17.
J Cancer Educ ; 30(1): 26-30, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24969319

RESUMO

The Asian Grocery Store-Based Cancer Education Program (the Program) is a proven strategy for promoting early breast cancer detection among Asian American women. The authors sought to test whether the same public health model can become an effective strategy for increasing the Asian community's awareness of the California Smokers' Helpline (the Helpline) and thereby, potentially decreasing this community's use of tobacco products. The new module, mainly staffed by four well-trained, volunteer undergraduates, explained the risks of first- and second-hand tobacco exposure and how to access the Helpline's services. A brochure, provided in English, Chinese, Korean, and Vietnamese (the Helpline's available Asian languages), was used to guide the bicultural, bilingual students' tobacco-related discussions with shoppers. The students' repeated presence at the nine partnering Asian grocery stores served as reminders of the Helpline's availability. In its first year of operation, the student trainers reached 1,052 men and 1,419 women with tobacco cessation messages. Equally important, the participating grocery stores' managers did not object to students telling their customers to quit using the tobacco products sold in their stores. The results suggest that the Program's tobacco cessation module is a viable, community-specific, public health strategy. It is also a strategy with the potential for applications to reduce other health threats.


Assuntos
Educação em Saúde , Serviços de Saúde/provisão & distribução , Disseminação de Informação , Abandono do Hábito de Fumar/etnologia , Abandono do Hábito de Fumar/estatística & dados numéricos , Americanos Asiáticos , California/etnologia , Feminino , Humanos , Masculino , Grupo com Ancestrais Oceânicos , Projetos Piloto
18.
Ann Thorac Surg ; 98(6): 1944-51; discussion 1951-2, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25282167

RESUMO

BACKGROUND: Current guidelines recommend routine imaging surveillance for patients with non-small cell lung cancer (NSCLC) after treatment. Little is known about surveillance patterns for patients with surgically resected early-stage lung cancer in the community at large. We sought to characterize surveillance patterns in a national cohort. METHODS: We conducted a retrospective study using the Surveillance, Epidemiology, and End-Results (SEER)-Medicare database (1995-2010). Patients with stage I/II NSCLC treated with surgical resection were included. Our primary outcome was receipt of imaging between 4 and 8 months after the surgical procedure. Covariates included demographics and comorbidities. RESULTS: Chest radiography (CXR) was the most frequent initial modality (60%), followed by chest computed tomography (CT) (25%). Positron emission tomography (PET) was least frequent as an initial imaging modality (3%). A total of 13% of patients received no imaging within the initial surveillance period. Adherence to National Comprehensive Cancer Network (NCCN) guidelines for imaging by overall prevalence was 47% for receipt of CT; however, rates of CT increased over time from 28% to 61% (p < 0.01). Reduced rates of CT were associated with stage I disease and surgical resection as the sole treatment modality. CONCLUSIONS: Imaging after definitive surgical treatment for NSCLC predominantly used CXR rather than CT. Most of this imaging is likely for surveillance, and in that context CXR has inferior detection rates for recurrence and new cancers. Adherence to guideline-recommended CT surveillance after surgical treatment is poor, but the reasons are multifactorial. Efforts to improve adherence to imaging surveillance must be coupled with greater evidence demonstrating improved long-term outcomes.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Diagnóstico por Imagem/métodos , Neoplasias Pulmonares/diagnóstico , Estadiamento de Neoplasias , Pneumonectomia , Programa de SEER , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Seguimentos , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Tomografia por Emissão de Pósitrons , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Tempo , Tomografia Computadorizada por Raios X , Washington/epidemiologia
19.
J Clin Oncol ; 32(30): 3428-35, 2014 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-25245440

RESUMO

PURPOSE: Optimizing evidence-based care to improve quality is a critical priority in the United States. We sought to examine adherence to imaging guideline recommendations for staging in patients with locally advanced lung cancer in a national cohort. METHODS: We identified 3,808 patients with stage IIB, IIIA, or IIIB lung cancer by using the national Department of Veterans Affairs (VA) Central Cancer Registry (2004-2007) and linked these patients to VA and Medicare databases to examine receipt of guideline-recommended imaging based on National Comprehensive Cancer Network and American College of Radiology Appropriateness Criteria. Our primary outcomes were receipt of guideline-recommended brain imaging and positron emission tomography (PET) imaging. We also examined rates of overuse defined as combined use of bone scintigraphy (BS) and PET, which current guidelines recommend against. All imaging was assessed during the period 180 days before and 180 days after diagnosis. RESULTS: Nearly 75% of patients received recommended brain imaging, and 60% received recommended PET imaging. Overuse of BS and PET occurred in 25% of patients. More advanced clinical stage and later year of diagnosis were the only clinical or demographic factors associated with higher rates of guideline-recommended imaging after adjusting for covariates. We observed considerable regional variation in recommended PET imaging and overuse of combined BS and PET. CONCLUSION: Receipt of guideline-recommended imaging is not universal. PET appears to be underused overall, whereas BS demonstrates continued overuse. Wide regional variation suggests that these findings could be the result of local practice patterns, which may be amenable to provider education efforts such as Choosing Wisely.


Assuntos
Neoplasias Pulmonares/patologia , Adulto , Idoso , Osso e Ossos/diagnóstico por imagem , Estudos de Coortes , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons
20.
J Cell Biol ; 205(5): 721-35, 2014 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-24891602

RESUMO

Clathrin-mediated endocytosis (CME) involves the recruitment of numerous proteins to sites on the plasma membrane with prescribed timing to mediate specific stages of the process. However, how choreographed recruitment and function of specific proteins during CME is achieved remains unclear. Using genome editing to express fluorescent fusion proteins at native levels and live-cell imaging with single-molecule sensitivity, we explored dynamin2 stoichiometry, dynamics, and functional interdependency with actin. Our quantitative analyses revealed heterogeneity in the timing of the early phase of CME, with transient recruitment of 2-4 molecules of dynamin2. In contrast, considerable regularity characterized the final 20 s of CME, during which ∼26 molecules of dynamin2, sufficient to make one ring around the vesicle neck, were typically recruited. Actin assembly generally preceded dynamin2 recruitment during the late phases of CME, and promoted dynamin recruitment. Collectively, our results demonstrate precise temporal and quantitative regulation of the dynamin2 recruitment influenced by actin polymerization.


Assuntos
Actinas/metabolismo , Clatrina/química , Dinamina II/metabolismo , Endocitose/fisiologia , Linhagem Celular , Separação Celular , Citoesqueleto/metabolismo , Citometria de Fluxo , Genoma , Humanos , Processamento de Imagem Assistida por Computador , Células K562 , Mutagênese , Estrutura Terciária de Proteína , Transferrina
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