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Transcatheter mitral valve repair should be considered for patients with severe secondary mitral regurgitation with symptomatic heart failure with reduced ejection fraction for symptom improvement and survival benefit. Patients with a higher severity of secondary mitral regurgitation relative to the degree of left ventricular dilation are more likely to benefit from transcatheter mitral valve repair. A multidisciplinary Heart Team should participate in patient selection for transcatheter mitral valve therapy.
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OBJECTIVE: Racial disparities in health care have come to the forefront. We hypothesized that Black race was associated with worse preoperative risk, lower repair rates, and worse outcomes among patients who underwent mitral valve surgery. METHODS: All patients who underwent mitral valve repair or replacement with or without coronary artery bypass grafting from 2011 to 2020 in a statewide collaborative database were stratified into 3 racial groups, White, Black, and other. Preoperative characteristics, procedure type, and outcomes were evaluated. RESULTS: A total of 9074 mitral valve operations were performed at 33 centers (Black 1009 [11.1%], White 7862 [86.6%]). Preoperative combined Society of Thoracic Surgeons morbidity and mortality was higher for Black patients (Black 32%, White 22%, other 23%, [P < .001]) because of a greater proportion of diabetes, hypertension, and chronic lung disease. White patients were more likely to undergo mitral repair (White 66%, Black 53.3%, other 57%; P < .001). Operative mortality was similar across racial groups (White 3.7%, Black 4.6%, other 4.5%; P = .36). After adjusting for preoperative factors, mitral etiology, and hospitals, race was not associated with mitral valve repair, complications, or mortality, but Black patients had higher odds of extended care facility utilization and readmission. CONCLUSIONS: Contrary to our hypothesis, there was no difference in the odds of repair or operative mortality across races after accounting for risk and etiology. However, Black patients were more likely to be readmitted after discharge. These findings support a greater focus on reducing disparities in mitral valve surgery.
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Implante de Prótese de Valva Cardíaca , Valva Mitral , Humanos , Valva Mitral/cirurgia , Resultado do Tratamento , Grupos Raciais , Ponte de Artéria Coronária , Hospitais , Implante de Prótese de Valva Cardíaca/métodosAssuntos
Insuficiência Cardíaca , Coração Auxiliar , Disfunção Ventricular Direita , Humanos , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/cirurgia , Função Ventricular Esquerda , Hemodinâmica , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/cirurgia , Disfunção Ventricular Direita/etiologia , Disfunção Ventricular Direita/terapia , Estudos RetrospectivosRESUMO
BACKGROUND: Recent guidelines for the treatment of moderate or severe ischemic mitral regurgitation (IMR) in patients undergoing coronary artery bypass grafting (CABG) have changed. This study assessed the real-world impact of changing guidelines on the management of IMR during CABG over time. We hypothesized that the utilization of mitral valve repair for IMR would decrease over time, whereas mitral valve replacement for severe IMR would increase. METHODS: Patients undergoing CABG in a statewide collaborative database (2011-2020) were stratified by severity of IMR. Trends in mitral valve repair or replacement were evaluated. To account for differences of the patients, propensity score-matched analyses were used to compare patients with and without mitral intervention. RESULTS: A total of 11,676 patients met inclusion criteria, including 1355 (11.6%) with moderate IMR and 390 (3.3%) with severe IMR. The proportion of patients undergoing mitral intervention for moderate IMR decreased over time (2011, 17.7%; 2020, 7.5%; Ptrend = .001), whereas mitral replacement for severe IMR remained stable (2011, 11.1%; 2020, 13.3%; Ptrend = .14). Major morbidity was higher for patients with moderate IMR who underwent mitral intervention (29.1% vs 19.9%; P = .005). In a propensity analysis of 249 well-matched pairs, there was no difference in major morbidity (29.3% with mitral intervention vs 23.7% without; P = .16) or operative mortality (1.2% vs 2.4%; P = .5). CONCLUSIONS: Consistent with recent guideline updates, patients with moderate IMR were less likely to undergo mitral repair. However, the rate of replacement for severe IMR did not change. Mitral intervention during CABG did not increase operative mortality or morbidity.
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Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Mitral , Isquemia Miocárdica , Humanos , Insuficiência da Valva Mitral/complicações , Insuficiência da Valva Mitral/cirurgia , Resultado do Tratamento , Ponte de Artéria Coronária , Isquemia Miocárdica/complicações , Isquemia Miocárdica/cirurgiaRESUMO
OBJECTIVE: Failure to rescue (FTR), defined as death after a complication, is recognized as a principal driver of variation in mortality among hospitals. We evaluated FTR as a quality metric in patients who received durable left ventricular assist devices (LVADs) using the Society of Thoracic Surgeons Interagency Registry for Mechanically Assisted Circulatory Support. METHODS: Data on 13,617 patients who received primary durable LVADs from April 2012 to October 2017 at 131 hospitals that performed at least 20 implants were analyzed from the Society of Thoracic Surgeons Interagency Registry for Mechanically Assisted Circulatory Support. Rates of major complications and FTR were compared across risk-adjusted in-hospital mortality terciles (low, medium, high) and hospital volume. Logistic regression was used to estimate expected FTR rates on the basis of patient factors for each major complication. RESULTS: The overall unadjusted in-hospital mortality rate was 6.96%. Risk-adjusted in-hospital mortality rates varied 3.1-fold across terciles (low, 3.3%; high, 10.3%; P trend <.001). Rates of major complications varied 1.1-fold (low, 34.0%; high, 38.8%; P < .0001). Among patients with a major complication, 854 died in-hospital for an FTR rate of 17.7%, with 2.8-fold variation across mortality terciles (low, 8.5%; high, 23.9%; P < .0001). FTR rates were highest for renal dysfunction requiring dialysis (45.3%) and stroke (36.5%). Higher average annual LVAD volume was associated with higher rates of major complications (<10 per year, 26.7%; 10-20 per year, 34.0%; 20-30 per year, 34.0%; >30 per year, 40.1%; P trend <.0001) whereas hospitals implanting <10 per year had the highest FTR rate (<10 per year, 23.5%; 10-20 per year, 16.5%; 20-30 per year, 17.0%; >30 per year, 17.9%; P = .03). CONCLUSIONS: FTR might serve as an important quality metric for durable LVAD implant procedures, and identifying strategies for successful rescue after complications might reduce hospital variations in mortality.
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Coração Auxiliar , Procedimentos Cirúrgicos Torácicos , Humanos , Coração Auxiliar/efeitos adversos , Complicações Pós-Operatórias , Diálise Renal , Hospitais , Mortalidade Hospitalar , Estudos RetrospectivosRESUMO
Importance: In 2020, the Centers for Medicare & Medicaid Services revised its national coverage determination, removing the requirement to obtain review from a Medicare-approved heart transplant center to implant a durable left ventricular assist device (LVAD) for bridge-to-transplant (BTT) intent at an LVAD-only center. The association between center-level transplant availability and access to heart transplant, the gold-standard therapy for advanced heart failure (HF), is unknown. Objective: To investigate the association of center transplant availability with LVAD implant strategies and subsequent heart transplant following LVAD implant before the Centers for Medicare & Medicaid Services policy change. Design, Setting, and Participants: A retrospective cohort study of the Society of Thoracic Surgeons Intermacs multicenter US registry database was conducted from April 1, 2012, to June 30, 2020. The population included patients with HF receiving a primary durable LVAD. Exposures: LVAD center transplant availability (LVAD/transplant vs LVAD only). Main Outcomes and Measures: The primary outcomes were implant strategy as BTT and subsequent transplant by 2 years. Covariates that might affect listing strategy and outcomes were included (eg, patient demographic characteristics, comorbidities) in multivariable models. Parameters for BTT listing were estimated using logistic regression with center-level random effects and for receipt of a transplant using a Cox proportional hazards regression model with death as a competing event. Results: The sample included 22â¯221 LVAD recipients with a median age of 59.0 (IQR, 50.0-67.0) years, of whom 17â¯420 (78.4%) were male and 3156 (14.2%) received implants at LVAD-only centers. Receiving an LVAD at an LVAD/transplant center was associated with a 79% increased adjusted odds of BTT LVAD designation (odds ratio, 1.79; 95% CI, 1.35-2.38; P < .001). The 2-year transplant rate following LVAD implant was 25.6% at LVAD/transplant centers and 11.9% at LVAD-only centers. There was an associated 33% increased rate of transplant at LVAD/transplant centers compared with LVAD-only centers (adjusted hazard ratio, 1.33; 95% CI, 1.17-1.51) with a similar hazard for death at 2 years (adjusted hazard ratio, 0.99; 95% CI, 0.90-1.08). Conclusions and Relevance: Receiving an LVAD at an LVAD-transplant center was associated with increased odds of BTT intent at implant and subsequent transplant receipt for patients at 2 years. The findings of this study suggest that Centers for Medicare & Medicaid Services policy change may have the unintended consequence of further increasing inequities in access to transplant among patients at LVAD-only centers.
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Insuficiência Cardíaca , Transplante de Coração , Coração Auxiliar , Humanos , Masculino , Idoso , Estados Unidos/epidemiologia , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , Medicare , Insuficiência Cardíaca/cirurgiaRESUMO
BACKGROUND: Improved health-related quality of life (HRQOL) is an important outcome following durable left ventricular assist device (LVAD) implant. However, half of pre-implant HRQOL data are incomplete in The Society of Thoracic Surgeons' Intermacs registry. Pre-implant HRQOL incompleteness may reflect patient status or hospital resources to capture HRQOL data. We hypothesized that pre-implant HRQOL incompleteness predicts 90 day outcomes and serves as a novel quality metric. METHODS: Risk factors for pre-implant HRQOL (EQ-5D-5L visual analog scale; 12-item Kansas City Cardiomyopathy Questionnaire "KCCQ") incompleteness were examined by stepwise logistic modeling. Direct standardization method was used to calculate adjusted incompleteness rates using a mixed effects logistic model. Hospitals were dichotomized as low or high based on median adjusted incompleteness rates. Andersen-Gill models were used to associate pre-implant HRQOL adjusted incompleteness rate with adverse events within 90 day post-implant. RESULTS: The study cohort included 14,063 patients receiving a primary LVAD (4/2012-8/2017). HRQOL incompleteness at high-rate hospitals was more often due to administrative reasons (risk difference, EQ-5D: 10.1%; KCCQ-12: 11.6%) and less likely due to patient reasons (risk difference, EQ-5D: -8.9%; KCCQ-12: -11.4%). A 10% increase in the adjusted pre-implant EQ-5D incompleteness rate was significantly associated with higher risk of infection-related mortality (HR: 1.09), infection (HR: 1.05), and renal dysfunction (HR: 1.03). A 10% increase in the adjusted pre-implant KCCQ-12 incompleteness rate was significantly associated with higher risk of infection (HR: 1.04). CONCLUSIONS: Hospital adjusted pre-implant HRQOL incompleteness was predictive of 90-day post-implant outcomes and may serve as a novel quality metric.
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Insuficiência Cardíaca , Coração Auxiliar , Estudos de Coortes , Insuficiência Cardíaca/cirurgia , Coração Auxiliar/efeitos adversos , Humanos , Qualidade de Vida , Sistema de Registros , Inquéritos e QuestionáriosRESUMO
Infections are widely prevalent in left ventricular assist device (LVAD) recipients and associated with adverse events including mortality and rehospitalizations. Current evidence examining factors associated with infections in this setting predominantly comprises single-center observational data. We performed a scoping review to systematically summarize all existing studies examining patient-related factors associated with infections after LVAD implantation. Studies published between 01/06 and 02/19 were identified through searching 5 bibliographic databases: PubMed, Scopus, EMBASE, CINAHL, and Web of Science Core Collection. Inclusion criteria required examination of patient-related factors associated with infections among recipients of contemporary implantable, continuous flow LVADs. Key study characteristics were extracted by four independent reviewers and current literature described narratively. All analyses took place between February 2019 and May 2021. A total of 31 studies met inclusion criteria. All included studies were observational, and most commonly focused on driveline infections (n = 17). Factors studied most commonly included body composition (n = 8), diabetes and other comorbidities (n = 8), and psychosocial/socio-economic factors (n = 6). Studies were frequently single-center with heterogeneity in definition of infectious outcomes as well as exposure variables. Patient race and sex did not correlate with infection risk. There was no consistent association noted between obesity, diabetes, or psychosocial/socio-economic factors and infections in LVAD recipients. Two studies reported a significant association between malnutrition and hypoalbuminemia and post implant infections. This review summarizes 31 studies that described patient-related factors associated with infection after LVAD implantation. Patient related comorbidities, especially body composition and diabetes, were most commonly evaluated, but were not consistently associated with infections after LVAD implantation.
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Insuficiência Cardíaca , Coração Auxiliar , Comorbidade , Coração Auxiliar/efeitos adversos , Humanos , Estudos RetrospectivosRESUMO
BACKGROUND: Patients undergoing left ventricular assist device (LVAD) implantation are at risk for death and postoperative adverse outcomes. Interhospital variability and concordance of quality metrics were assessed using the Society of Thoracic Surgeons Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs). METHODS: A total of 22 173 patients underwent primary, durable LVAD implantation across 160 hospitals from 2012 to 2020, excluding hospitals performing <10 implant procedures. Observed and risk-adjusted operative mortality rates were calculated for each hospital. Outcomes included operative and 90-day mortality, a composite of adverse events (operative mortality, bleeding, stroke, device malfunction, renal dysfunction, respiratory failure), and secondarily failure to rescue. Rates are presented as median (interquartile range [IQR]). Hospital performance was evaluated using observed-to-expected (O/E) ratios for mortality and the composite outcome. RESULTS: Interhospital variability existed in observed (median, 7.2% [IQR, 5.1%-9.6%]) mortality. The rates of adverse events varied across hospitals: major bleeding, 15.6% (IQR, 11.4%-22.4%); stroke, 3.1% (IQR, 1.6%-4.7%); device malfunction, 2.4% (IQR, 0.8%-3.7%); respiratory failure, 10.5% (IQR, 4.6%-15.7%); and renal dysfunction, 6.4% (IQR, 3.2%-9.6%). The O/E ratio for operative mortality varied from 0.0 to 6.1, whereas the O/E ratio for the composite outcome varied from 0.28 to 1.99. Hospital operative mortality O/E ratios were more closely correlated with the 90-day mortality O/E ratio (r = 0.74) than with the composite O/E ratio (r = 0.12). CONCLUSIONS: This study reported substantial interhospital variability in performance for hospitals implanting durable LVADs. These findings support the need to (1) report hospital-level performance (mortality, composite) and (2) undertake benchmarking activities to reduce unwarranted variability in outcomes.
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Insuficiência Cardíaca , Coração Auxiliar , Nefropatias , Insuficiência Respiratória , Acidente Vascular Cerebral , Cirurgiões , Benchmarking , Feminino , Coração Auxiliar/efeitos adversos , Humanos , Nefropatias/etiologia , Masculino , Sistema de Registros , Insuficiência Respiratória/etiologia , Estudos Retrospectivos , Acidente Vascular Cerebral/etiologia , Resultado do TratamentoRESUMO
BACKGROUND: Infections are the most common complication in recipients of durable left ventricular assist devices (LVAD) and are associated with increased morbidity, mortality, and expenditures. The existing literature examining factors associated with infection in LVAD recipients is limited and principally comprises single-center studies. This scoping review synthesizes all available evidence related to identifying modifiable, non-patient factors associated with infections among LVAD recipients. METHODS: Published studies were identified through searching 5 bibliographic databases: PubMed, Scopus, EMBASE, CINAHL, and Web of Science Core Collection. Inclusion criteria required examination of factors associated with infections among recipients of contemporary, implantable, continuous flow LVADs. Key study characteristics were extracted by 4 independent reviewers and current literature described narratively. The Systems Engineering Initiative for Patient Safety (SEIPS) model was used to develop a taxonomy for non-patient related factors (e.g., tasks, tools, technologies, organization, and environment) associated with infections following LVAD implantation. All analyses took place between February 2019 and May 2021. FINDINGS: A total of 43 studies met inclusion criteria. The majority of included studies were observational (n = 37), single-center (n = 29), from the U.S. (n = 38), and focused on driveline infections (n = 40). Among the 22 evaluated sub-domains of non-patient related factors, only two: increasing center experience and establishing a silicone-skin interface at the driveline exit site, were identified as consistently being associated with a lower risk of infection. CONCLUSION: This review identified 43 studies that described non-patient related factors associated with infection in LVAD recipients. Only two factors were consistently associated with lower infection risk in LVAD recipients: increasing experience and establishing a silicone-skin interface at driveline exit site. The large variability in reporting across multiple studied interventions limited the ability to discern their effectiveness.
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Coração Auxiliar/efeitos adversos , Infecções Relacionadas à Prótese/etiologia , HumanosRESUMO
There are few reports of HeartMate 3 pump thrombosis, with existing reports relating to outflow occlusion or early perioperative thrombosis. We present a case of late pump thrombosis requiring pump exchange.
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Insuficiência Cardíaca , Coração Auxiliar , Trombose , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/cirurgia , Coração Auxiliar/efeitos adversos , Humanos , Estudos Retrospectivos , Trombose/etiologiaRESUMO
PURPOSE: Timely and high-quality feedback is important in cardiothoracic (CT) surgery education. Feedback on operative proficiency is an area for improvement in CT surgery programs. Traditional evaluations significantly lag behind operative interactions. We hypothesized that use of the System for Improving and Measuring Procedural Learning (SIMPL) app would improve operative feedback for trainees. METHODS: Use of SIMPL was evaluated from December 2018 to January, 2021 within an academic CT surgery training program. Ratings include level of supervision, complexity of the operation, and trainee performance. Completion was limited to 72 h after the operation. Descriptive statistics of the users and ratings are presented. RESULTS: Over 28 months, 816 evaluations were completed, and of these, 495 had a rating from both the faculty and trainee. There were 19 trainees representing post-graduate years 1-8 and 19 faculty members who received or submitted at least one evaluation over the study period. The number of evaluations for each trainee ranged from 1 to 166 and from 1 to 81 for each of the faculty. The response rate for faculty ranged from 0% to 100%. "Active help" was the most common type of supervision (50.7% by the faculty, 60.4% from the trainees). CONCLUSIONS: Use of SIMPL within a CT surgery training program was feasible and engagement was observed from both trainees and faculty. SIMPL provided trainees with timely, concise feedback on operative performance. Further work will focus on correlating SIMPL ratings with pre-existing assessments of performance.
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Internato e Residência , Aplicativos Móveis , Competência Clínica , Estudos de Viabilidade , Humanos , SmartphoneRESUMO
BACKGROUND: After completing traditional fellowship or integrated residency in cardiothoracic surgery, many trainees spend time in nonaccredited "super fellowships." The prevalence and motivations for pursuing super fellowships are unknown. METHODS: A survey was distributed to all 776 cardiothoracic surgery graduates who completed training between 2008 and 2019. The number of graduates was used as the denominator to calculate response rate. Comparisons between responses were made using Fisher's exact test. RESULTS: Over an 8-week period, 261 surveys were completed with a response rate of 34%. The majority were traditional graduates (75%), for example, not integrated residents, and of those, 64% did a 2-year program. The majority (60%) did not pursue super fellowships. Among those who did complete a super fellowship, areas of training included congenital, transplantation, aortic pathology, valvular disease, and other. Among the 90 who completed super fellowships, reasons included "congenital" (34%), "felt training inadequate" (28%), "required for position" (24%), "personal" (6%), and "other" (8%). Among the 25 who selected "training inadequate," 32% focused in general thoracic-related areas. There was no relationship between length of traditional training (2 vs 3 years) and completing additional training (P = .17), but there was a significant association between completing a traditional track versus integrated residency and pursuing a super fellowship (P = .02). CONCLUSIONS: Additional training in cardiothoracic surgery is common. The reasons for further instruction are varied but relate to readiness and need for specialized skills. Program directors should consider employers' needs to ensure trainees graduate with the necessary skills for future practice.
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Bolsas de Estudo , Motivação , Cirurgia Torácica/educação , Autorrelato , Estados UnidosRESUMO
BACKGROUND: Sarcopenia, visceral fat volume, and bone density have been associated with lung cancer survival. We developed a morphomic index based on computed tomographic measurements of these components, and assessed its relationship to survival after lung cancer resection. METHODS: Patients who underwent lung cancer resection from 1995 to 2014 were evaluated. A morphomic index (range of 0 to 3) was developed as the sum of the scores for three body components-dorsal muscle area, vertebral trabecular bone density, and visceral fat area-measured at vertebral levels T10 to T12, with a point assigned to each component when in the lowest tercile. The relationship of the morphomic index to overall survival was assessed by the log rank test. Overall survival was assessed using Cox proportional hazards models adjusted for relevant covariates. RESULTS: We included 944 patients (451 women; 48%). The mean age was 66.4 ± 10.3 years. Median follow-up was 4.5 years. Median survival was associated with the morphomic index scores on univariate analysis (P < .001). Morphomic index scores of 2 (P = .026) and 3 (P = .004) referenced to score 0 or 1 were independent predictors of survival on Cox regression analysis. CONCLUSIONS: A morphomic index is an independent predictor of survival after lung cancer resection. The index may help in calibrating patient expectations and in shared decision making regarding lung cancer surgery.
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Composição Corporal , Neoplasias Pulmonares/cirurgia , Estadiamento de Neoplasias , Pneumonectomia , Medição de Risco/métodos , Idoso , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Masculino , Período Pós-Operatório , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: The purpose of this study was to identify morphomic factors on standard, pretransplantation computed tomography (CT) scans associated with outcomes after lung transplantation. METHODS: A retrospective review of 200 patients undergoing lung transplantation at a single institution from 2003 to 2014 was performed. CT scans obtained within 1 year before transplantation underwent morphomic analysis. Morphomic characteristics included lung, dorsal muscle group, bone, and subcutaneous and visceral fat area and density. Patient data were gathered from institutional and United Network for Organ Sharing databases. Outcomes, including initial ventilator support greater than 48 hours, length of stay, and survival, were evaluated using univariate and multivariable analyses. RESULTS: On multivariable Cox regression, subcutaneous fat/total body area (hazard ratio [HR] 0.60, p = 0.001), lung density 3 volume (HR 0.67, p = 0.013), and creatinine (HR 4.37, p = 0.010) were independent predictors of survival. Initial ventilator support more than 48 hours was associated with decreased vertebral body to linea alba distance (odds ratio [OR] 0.49, p = 0.002) and Zubrod score 4 (OR 14.0, p < 0.001). Increased bone mineral density (p < 0.001) and increased cross-sectional body area (p < 0.001) were associated with decreased length of stay, whereas supplemental oxygen (p < 0.001), bilateral transplantation (p = 0.002), cardiopulmonary bypass (p < 0.001), and Zubrod score 3 (p < 0.001) or 4 (p = 0.040) were associated with increased length of stay. CONCLUSIONS: Morphomic factors associated with lower metabolic reserve and frailty, including decreased subcutaneous fat, bone density, and body dimensions were independent predictors of survival, prolonged ventilation, and increased length of stay. Analytic morphomics using pretransplantation CT scans may improve recipient selection and risk stratification.
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Gordura Intra-Abdominal/diagnóstico por imagem , Transplante de Pulmão , Complicações Pós-Operatórias/diagnóstico , Insuficiência Respiratória/cirurgia , Medição de Risco , Tomografia Computadorizada por Raios X/métodos , Estudos Transversais , Feminino , Seguimentos , Humanos , Incidência , Masculino , Michigan/epidemiologia , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Período Pré-Operatório , Prognóstico , Radiografia Torácica , Insuficiência Respiratória/diagnóstico , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Fatores de TempoRESUMO
Erythropoietin (Epo) is used in clinical settings to enhance hematopoietic function and to improve the quality of life for patients undergoing chemotherapy by reducing fatigue and the need for transfusions. However, several meta-analyses have revealed that Epo treatments are associated with an increased risk of mortality in cancer patients. In this study, we examined the role of Epo in prostate cancer (PCa) progression, using in vitro cell culture systems and in vivo bone metastatic assays. We found that Epo did not stimulate the proliferation of PCa cell lines, but did protect PCa cells from apoptosis. In animal models of PCa metastasis, no evidence was found to support the hypothesis that Epo enhances metastasis. Together, these findings suggest that Epo may be useful for treating severe anemia in PCa patients without increasing metastatic risk.
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Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Proliferação de Células/efeitos dos fármacos , Eritropoetina/uso terapêutico , Metástase Neoplásica/prevenção & controle , Neoplasias da Próstata/complicações , Neoplasias da Próstata/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Linhagem Celular Tumoral , Citometria de Fluxo , Humanos , Masculino , Camundongos , Camundongos SCIDRESUMO
HSC homing, quiescence, and self-renewal depend on the bone marrow HSC niche. A large proportion of solid tumor metastases are bone metastases, known to usurp HSC homing pathways to establish footholds in the bone marrow. However, it is not clear whether tumors target the HSC niche during metastasis. Here we have shown in a mouse model of metastasis that human prostate cancer (PCa) cells directly compete with HSCs for occupancy of the mouse HSC niche. Importantly, increasing the niche size promoted metastasis, whereas decreasing the niche size compromised dissemination. Furthermore, disseminated PCa cells could be mobilized out of the niche and back into the circulation using HSC mobilization protocols. Finally, once in the niche, tumor cells reduced HSC numbers by driving their terminal differentiation. These data provide what we believe to be the first evidence that the HSC niche serves as a direct target for PCa during dissemination and plays a central role in bone metastases. Our work may lead to better understanding of the molecular events involved in bone metastases and new therapeutic avenues for an incurable disease.