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PURPOSE: With DCIS incidence on the rise, up to 30% of patients undergo mastectomy for Ductal carcinoma in situ (DCIS) (Nash and Hwang, in: Ann Surg Oncol 30(6):3206-3214, 2023). Local recurrence rates after mastectomy for DCIS are reportedly low, but risk factors for recurrence are not known (Kim et al., in: J Cancer Res Ther 16(6):1197-1202, 2020). We aim to define risk factors associated with ipsilateral breast cancer recurrence in patients undergoing mastectomy for DCIS. METHODS: We aimed to identify risk factors that may contribute to recurrence of breast cancer following mastectomy for pure DCIS. We hypothesized that close or positive mastectomy margins, age at diagnosis, extent of breast disease and mutation carriers would be associated with increased risk of recurrence. We performed a retrospective chart review of patients who underwent unilateral or bilateral mastectomies for pure DCIS at a single academic tertiary referral center from 2013 to 2023. RESULTS: There were 165 patients who met inclusion criteria with an average length of follow-up of 39.9 months. On final surgical pathology, the average span of DCIS was 33.7 mm (± 24.6 mm). Hormone receptor positive disease was identified in 80.6% of the patient cohort. For margin status, 23 patients (14%) had < 1 mm margins on final pathology and of those, 1 received adjuvant radiation therapy and 4 returned to the OR for re-excision. Only 1 (0.6%) patient had ipsilateral disease recurrence during the study period. CONCLUSION: Recurrence after mastectomy for pure DCIS is a rare event and in our study sample, only one recurrence occurred. Risk factors for recurrence appear unrelated to margin status, age, extent of DCIS, or pathogenic mutation (ElSherif et al., in Am J Surg 226(5):646-651, 2023).
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BACKGROUND AND AIMS: For patients with congenitally corrected transposition of the great arteries (ccTGA), factors associated with progression to end-stage congestive heart failure (CHF) remain largely unclear. METHODS: This multicentre, retrospective cohort study included adults with ccTGA seen at a congenital heart disease centre. Clinical data from initial and most recent visits were obtained. The composite primary outcome was mechanical circulatory support, heart transplantation, or death. RESULTS: From 558 patients (48% female, age at first visit 36 ± 14.2 years, median follow-up 8.7 years), the event rate of the primary outcome was 15.4 per 1000 person-years (11 mechanical circulatory support implantations, 12 transplantations, and 52 deaths). Patients experiencing the primary outcome were older and more likely to have a history of atrial arrhythmia. The primary outcome was highest in those with both moderate/severe right ventricular (RV) dysfunction and tricuspid regurgitation (n = 110, 31 events) and uncommon in those with mild/less RV dysfunction and tricuspid regurgitation (n = 181, 13 events, P < .001). Outcomes were not different based on anatomic complexity and history of tricuspid valve surgery or of subpulmonic obstruction. New CHF admission or ventricular arrhythmia was associated with the primary outcome. Individuals who underwent childhood surgery had more adverse outcomes than age- and sex-matched controls. Multivariable Cox regression analysis identified older age, prior CHF admission, and severe RV dysfunction as independent predictors for the primary outcome. CONCLUSIONS: Patients with ccTGA have variable deterioration to end-stage heart failure or death over time, commonly between their fifth and sixth decades. Predictors include arrhythmic and CHF events and severe RV dysfunction but not anatomy or need for tricuspid valve surgery.
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Insuficiência Cardíaca , Transposição dos Grandes Vasos , Insuficiência da Valva Tricúspide , Disfunção Ventricular Direita , Adulto , Humanos , Feminino , Criança , Adulto Jovem , Pessoa de Meia-Idade , Masculino , Transposição das Grandes Artérias Corrigida Congenitamente , Estudos Retrospectivos , Transposição dos Grandes Vasos/complicações , Transposição dos Grandes Vasos/cirurgia , Insuficiência da Valva Tricúspide/complicações , Disfunção Ventricular Direita/complicações , Insuficiência Cardíaca/complicaçõesRESUMO
BACKGROUND: Luminal narrowing, suspected secondary to thrombus, occurs within stent grafts at an unclear incidence after thoracic endovascular aortic repair (TEVAR). The significance of this phenomenon has not been determined, nor have the risk factors for development of intragraft luminal narrowing. Small graft diameter is hypothesized to be a risk factor for the development of ingraft stenosis. METHODS: A retrospective analysis was performed of a multicenter healthcare system including all patients who underwent TEVAR between July 2011 and July 2019 with at least 1 year of subsequently available surveillance contrast-enhanced computed tomography imaging. Standard demographic, preoperative, intraoperative, and postoperative variables were collected. Measurements were obtained via direct off-line images from computed tomography scans. Patent intragraft diameters were compared with baseline and interval change values were normalized to time to follow-up. The primary outcome measure was annual rate of intragraft luminal narrowing. RESULTS: There were 208 patients who met the inclusion criteria (94 women, 114 men) with a median follow-up of 822 days. The mean annual rate of percent intragraft diameter reduction was 10.5 ± 7.7% for women and 7.6 ± 5.6% for men (P = .0026). Multivariate analysis demonstrated female gender (P = .0283), preoperative diagnosis of hypertension (P = .0449), and need for coverage of the left subclavian artery (P = .0328) were all significant predictors of intragraft luminal narrowing. Small aortic diameters were not found to be associated independently with ingraft luminal narrowing nor was the concomitant use of antiplatelet or anticoagulation medications. Significant amounts of ingraft luminal narrowing, defined as a greater than 20% intragraft diameter decrease, were associated with an increased need for any reintervention, including for malperfusion, endoleak, and symptomatic aneurysm (P = .0249). Kaplan-Meier estimates demonstrated a significant gender-associated difference in high rates of intragraft luminal narrowing (P = .00189). CONCLUSIONS: In this analysis, female gender is shown to be a significant nonmodifiable risk factor for intragraft luminal narrowing after TEVAR. The development of this phenomenon is not benign; as such, these findings were associated with an increased need for reintervention. This finding may be attributable to differences in aortic compliance or gender-associated differences in coagulation pathways and merits further investigation. Surveillance after thoracic stent grafting must account for patient-specific variations in complication risk.
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Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/cirurgia , Implante de Prótese Vascular/efeitos adversos , Oclusão de Enxerto Vascular/epidemiologia , Adulto , Idoso , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/cirurgia , Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/instrumentação , Angiografia por Tomografia Computadorizada , Feminino , Oclusão de Enxerto Vascular/diagnóstico , Oclusão de Enxerto Vascular/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Stents/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Left ventricular (LV) wall thickening occurs in patients following thoracic endovascular aortic repair (TEVAR). Clinical consequences of cardiovascular (CV) remodeling may be more significant younger patients with longer anticipated life spans. Risk factors for CV remodeling following TEVAR are unknown but may be related to graft size. METHODS: A retrospective analysis was performed of a multicenter healthcare system including patients aged ≤60 who underwent TEVAR between 2011 and 2019 with at least 1 year follow-up computed tomography angiography imaging available. Standard perioperative variables, native aortic diameter, and stent graft specifications were collected. Graft oversizing was calculated by dividing proximal graft diameter by proximal aortic diameter on preoperative imaging. Posterior LV wall thickness was measured at baseline and interval increases were normalized to time-to-follow-up. Primary outcome was annual rate of posterior LV wall thickening. RESULTS: One hundred one patients met inclusion criteria with a mean (SD) follow-up time of 1270 (693) days. Overall mean (SD) rate of LV wall thickness change was 0.534 (0.750) mm per year. Mean (SD) absolute LV wall thickness at most recent follow-up was 10.97 (2.85) mm for men, 9.69 (2.03) mm for women. Multivariate analysis demonstrated that higher rates of LV wall thickening were associated with narrower graft diameters (P = 0.0311). Greater absolute LV wall thickness at follow-up was associated with narrower grafts (P= 0.0155) and greater graft oversizing (P= 0.0376). Logistic regression demonstrated individuals who met criteria for LV hypertrophy were more likely to have narrower stent-grafts (P= 0.00798) and greater graft oversizing (P= 0.0315). CONCLUSIONS: LV wall thickening occurred to a greater degree in individuals with narrower stent-grafts and higher rates of graft oversizing. This has significant implications for long-term cardiovascular health in younger patients may undergo TEVAR for atypical indications. Particular attention should be paid to long-term effects of stent-graft oversizing when selecting grafts in such populations.
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Aorta Torácica/cirurgia , Doenças da Aorta/cirurgia , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Procedimentos Endovasculares/instrumentação , Hipertrofia Ventricular Esquerda/etiologia , Stents , Função Ventricular Esquerda , Remodelação Ventricular , Adulto , Fatores Etários , Aorta Torácica/diagnóstico por imagem , Doenças da Aorta/diagnóstico por imagem , Implante de Prótese Vascular/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
Using the 12-item World Health Organization Disability Assessment Schedule (WHODAS-12), we measured the prevalence of disability in all eligible patients during a 4-month period who were presenting for preoperative evaluation at a US Veterans Affairs hospital. Overall disability was at least moderate in more than half of these patients (total n = 472 at Durham, NC). Two of the 6 WHODAS domains, "Getting Around" and "Participation in Society," contributed most to the overall scores-25% and 20%, respectively. Further studies are needed to determine the impact of domain-specific disabilities on postoperative outcomes and to identify potential interventions to address these vulnerabilities.
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Avaliação da Deficiência , Período Pré-Operatório , Veteranos , Adulto , Idoso , Idoso de 80 Anos ou mais , Pessoas com Deficiência , Feminino , Hospitais de Veteranos , Humanos , Masculino , Pessoa de Meia-Idade , Limitação da Mobilidade , Prevalência , Comportamento Social , Inquéritos e Questionários , Estados Unidos , United States Department of Veterans AffairsRESUMO
BACKGROUND: Patients with transposition of the great arteries (TGA) and systemic right ventricle often confront significant adverse cardiac events. The prognostic significance of invasive hemodynamic parameters in this context remains uncertain. Our hypothesis is that the aortic pulsatility index and hemodynamic profiling utilizing invasive measures provide prognostic insights for patients with TGA and a systemic right ventricle. METHODS: This retrospective multicenter cohort study encompasses adults with TGA and a systemic right ventricle who underwent cardiac catheterization. Data collection, spanning from 1994 to 2020, encompasses clinical and hemodynamic parameters, including measured and calculated values such as pulmonary capillary wedge pressure, aortic pulsatility index, and cardiac index. Pulmonary capillary wedge pressure and cardiac index values were used to establish 4 distinct hemodynamic profiles. A pulmonary capillary wedge pressure of ≥15 mmâ Hg indicated congestion, termed wet, while a cardiac index <2.2 L/min per m2 signified inadequate perfusion, labeled cold. The primary outcome comprised a composite of all-cause death, heart transplantation, or the requirement for mechanical circulatory support. RESULTS: Of 1721 patients with TGA, 242 individuals with available invasive hemodynamic data were included. The median follow-up duration after cardiac catheterization was 11.4 (interquartile range, 7.5-15.9) years, with a mean age of 38.5±10.8 years at the time of cardiac catheterization. Among hemodynamic parameters, an aortic pulsatility index <1.5 emerged as a robust predictor of the primary outcome, with adjusted hazard ratios of 5.90 (95% CI, 3.01-11.62; P<0.001). Among the identified 4 hemodynamic profiles, the cold/wet profile was associated with the highest risk for the primary outcome, with an adjusted hazard ratio of 3.83 (95% CI, 1.63-9.02; P<0.001). CONCLUSIONS: A low aortic pulsatility index (<1.5) and the cold/wet hemodynamic profile are linked with an elevated risk of adverse long-term cardiac outcomes in patients with TGA and systemic right ventricle.
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Cateterismo Cardíaco , Ventrículos do Coração , Hemodinâmica , Transposição dos Grandes Vasos , Humanos , Masculino , Feminino , Transposição dos Grandes Vasos/fisiopatologia , Transposição dos Grandes Vasos/cirurgia , Estudos Retrospectivos , Hemodinâmica/fisiologia , Adulto , Prognóstico , Ventrículos do Coração/fisiopatologia , Ventrículos do Coração/diagnóstico por imagem , Pessoa de Meia-Idade , Função Ventricular Direita/fisiologia , Pressão Propulsora Pulmonar/fisiologiaRESUMO
Cancer progression depends on an accumulation of metastasis-supporting physiological changes, which are regulated by cell-signaling molecules. In this regard, a disintegrin and metalloproteinase 8 (Adam8) is a transmembrane glycoprotein that is selectively expressed and induced by a variety of inflammatory stimuli. In this study, we identified Adam8 as a sox2-dependent protein expressed in MDA-MB-231 breast cancer cells when cocultured with mesenchymal-stem-cell-derived myofibroblast-like cancer-associated fibroblasts (myCAF). We have previously found that myCAF-induced cancer stemness is required for the maintenance of the myCAF phenotype, suggesting that the initiation and maintenance of the myCAF phenotype require distinct cell-signaling crosstalk pathways between cancer cells and myCAF. Adam8 was identified as a candidate secreted protein induced by myCAF-mediated cancer stemness. Adam8 has a known sheddase function against which we developed an RNA aptamer, namely, Adam8-Apt1-26nt. The Adam8-Apt1-26nt-mediated blockade of the extracellular soluble Adam8 metalloproteinase domain abolishes the previously initiated myCAF phenotype, or, termed differently, blocks the maintenance of the myCAF phenotype. Consequently, cancer stemness is significantly decreased. Xenograft models show that Adam8-Apt-1-26nt administration is associated with decreased tumor growth and metastasis, while flow cytometric analyses demonstrate a significantly decreased fraction of myCAF after Adam8-Apt-1-26nt treatment. The role of soluble Adam8 in the maintenance of the myCAF phenotype has not been previously characterized. Our study suggests that the signal pathways for the induction or initiation of the myCAF phenotype may be distinct from those involved with the maintenance of the myCAF phenotype.
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BACKGROUND: For patients with d-loop transposition of the great arteries (d-TGA) with a systemic right ventricle after an atrial switch operation, there is a need to identify risks for end-stage heart failure outcomes. OBJECTIVES: The authors aimed to determine factors associated with survival in a large cohort of such individuals. METHODS: This multicenter, retrospective cohort study included adults with d-TGA and prior atrial switch surgery seen at a congenital heart center. Clinical data from initial and most recent visits were obtained. The composite primary outcome was death, transplantation, or mechanical circulatory support (MCS). RESULTS: From 1,168 patients (38% female, age at first visit 29 ± 7.2 years) during a median 9.2 years of follow-up, 91 (8.8% per 10 person-years) met the outcome (66 deaths, 19 transplantations, 6 MCS). Patients experiencing sudden/arrhythmic death were younger than those dying of other causes (32.6 ± 6.4 years vs 42.4 ± 6.8 years; P < 0.001). There was a long duration between sentinel clinical events and end-stage heart failure. Age, atrial arrhythmia, pacemaker, biventricular enlargement, systolic dysfunction, and tricuspid regurgitation were all associated with the primary outcome. Independent 5-year predictors of primary outcome were prior ventricular arrhythmia, heart failure admission, complex anatomy, QRS duration >120 ms, and severe right ventricle dysfunction based on echocardiography. CONCLUSIONS: For most adults with d-TGA after atrial switch, progress to end-stage heart failure or death is slow. A simplified prediction score for 5-year adverse outcome is derived to help identify those at greatest risk.
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Transposição das Grandes Artérias , Insuficiência Cardíaca , Transposição dos Grandes Vasos , Adulto , Transposição das Grandes Artérias/efeitos adversos , Artérias , Feminino , Seguimentos , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/etiologia , Humanos , Masculino , Estudos Retrospectivos , Transposição dos Grandes Vasos/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: Care Assessment of Need (CAN) scores predicting 90-day mortality and hospitalization are automatically computed each week for patients receiving care at Veterans Health Administration facilities. While currently used only by primary care teams for care coordination, we explored their value as a perioperative risk stratification tool before major elective surgery. METHODS: We collected relevant demographic and perioperative data along with perioperative CAN scores for veterans who underwent total knee replacement between July 2014 and December 2015. We examined score distribution, relationships of preoperative CAN 1-year mortality scores with 1-year postoperative mortality and index hospital length of stay (LOS), and patterns of mortality. RESULTS: Among 8206 patients, 1-year mortality was 1.4% (110 patients), and CAN scores exhibited near-normal distribution. Median scores among survivors were significantly higher than those of in nonsurvivors (45 vs 75; P < .001). The Kaplan-Meier curves showed an approximately 4-fold higher rate of death at 1 year in the highest tercile for 1-year mortality CAN scores compared with those with lower scores (2.0% vs 0.5% respectively; P < .001). Locally estimated scatterplot smoothing curves revealed a significant and nonlinear increase in hospital LOS across preoperative CAN scores. CONCLUSIONS: Although designed for ambulatory care use, CAN scores can identify patients at high risk for mortality and extended hospital LOS in an elective surgery population. The CAN scores may prove valuable in supporting informed decision making and preoperative planning in high-risk and vulnerable populations. Further study is needed to confirm the validity of CAN scores and compare them to other more widely used surgical risk calculators.
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BACKGROUND: Eight novel virtual surgery electives (VSEs) were developed and implemented in April-May 2020 for medical students forced to continue their education remotely due to COVID-19. METHODS: Each VSE was 1-2 weeks long, contained specialty-specific course objectives, and included a variety of teaching modalities. Students completed a post-course survey to assess changes in their interest and understanding of the specialty. Quantitative methods were employed to analyze the results. RESULTS: Eighty-three students participated in the electives and 67 (80.7%) completed the post-course survey. Forty-six (68.7%) respondents reported "increased" or "greatly increased" interest in the course specialty completed. Survey respondents' post-course understanding of each specialty increased by a statistically significant amount (p-value = <0.0001). CONCLUSION: This initial effort demonstrated that VSEs can be an effective tool for increasing medical students' interest in and understanding of surgical specialties. They should be studied further with more rigorous methods in a larger population.
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Educação a Distância/métodos , Educação de Graduação em Medicina/métodos , Especialidades Cirúrgicas/educação , COVID-19/epidemiologia , COVID-19/prevenção & controle , Escolha da Profissão , Controle de Doenças Transmissíveis/normas , Currículo , Educação a Distância/organização & administração , Educação a Distância/normas , Educação a Distância/estatística & dados numéricos , Educação de Graduação em Medicina/organização & administração , Educação de Graduação em Medicina/normas , Educação de Graduação em Medicina/estatística & dados numéricos , Avaliação Educacional/estatística & dados numéricos , Humanos , Aprendizagem , Pandemias/prevenção & controle , Avaliação de Programas e Projetos de Saúde , Smartphone , Estudantes de Medicina/estatística & dados numéricos , Comunicação por Videoconferência/instrumentaçãoRESUMO
BACKGROUND: Robotics offers improved ergonomics, enhanced visualization, and increased dexterity. Disadvantages include startup, maintenance and instrument costs. Surgeon education notwithstanding, we hypothesized that robotic inguinal hernia repair carries minimal advantages over the open or laparoscopic approach in the inpatient setting. METHODS: The HCUP-SID and AHA datasets were queried for inguinal hernia repair codes. Hospital and patient demographic, financial and comorbidity data were evaluated. Data are presented as mean⯱â¯SEM. RESULTS: 36396 cases (27776 Open, 7104 Laparoscopic and 1516 Robotic) were identified. Total costs were: $13595⯱â¯104 (Open), $13581⯱â¯176 (Laparoscopic) and $18494⯱â¯323 (Robotic). (pâ¯<â¯0.0001 Robotic vs Open, Robotic vs Laparoscopic) Robotic costs were 38% greater than that of the Open and Laparoscopic subsets (pâ¯<â¯0.001 Robotic vs. Open and Laparoscopic). The Open, Laparoscopic and Robotic subsets' length of stay were 4.2, 3.2 and 2.3 days, respectively. (pâ¯<â¯0.0001 among Open, Laparoscopic and Robotic). CONCLUSION: The Robotic approach to the inguinal hernia repair had the lowest length of stay, despite having the highest costs. The benefits of robotic surgery in inguinal hernia repair are unclear in the inpatient setting.
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Hérnia Inguinal/cirurgia , Herniorrafia/métodos , Pacientes Internados , Laparoscopia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Adolescente , Adulto , Idoso , Feminino , Herniorrafia/economia , Humanos , Laparoscopia/economia , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Robóticos/economia , Estados UnidosRESUMO
BACKGROUND: Robotics offers improved ergonomics, visualization, instrument articulation, and tremor filtration. Disadvantages include startup cost and system breakdown. Surgeon education notwithstanding, we hypothesize that robotic inguinal hernia repair carries minimal advantages over the laparoscopic or open approach. METHODS: The 2009-2015 Healthcare Cost and Utilization Project-State Ambulatory Surgery and Services and American Hospital Association Annual Health data sets from Florida were queried for open, laparoscopic, and robotic inguinal hernia repairs. Hospital and patient demographic, financial, and comorbidity data (26 total variables) were evaluated. Data are presented as mean ± SEM; p < 0.05 was considered significant. RESULTS: We identified 103,183 cases (63,375 open, 38,886 laparoscopic, and 922 robotic). Patient characteristics were the following: male, white, aged 51 to 70 years, nongovernmental and not-for-profit hospitals, grouped Charlson Comorbidity Category = 0, private insurance coverage, median income quartile 3 (4 = highest), and routine discharge disposition (all, p < 0.05). Total charges were: $18,261 ± $38 (open), $25,223 ± $60 (laparoscopic), and $45,830 ± $1,023 (robot) (p < 0.0001 robot vs open, robot vs laparoscopic, and laparoscopic vs open). Top factors associated with open procedures (area under the curve 0.785): hospital is investor owned for profit, self-pay, black, Latino, and Medicaid; with laparoscopic procedures (area under the curve 0.771): private insurance, median income quartile 4 (highest), median income quartile 3, median income quartile 2, and nongovernmental, not-for-profit hospitals; and with robotic procedures (area under the curve 0.936): Charlson Comorbidity Category = 2, Charlson Comorbidity Category = 1, median income quartile 3, median income quartile 2, and age. CONCLUSIONS: Robotic surgery has increased charges and is performed in sicker, higher-income patients. The open approach is more apt to be performed in black/Hispanic, self-pay patients, and for-profit hospitals. The role for robotic inguinal hernia repair is undefined.
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Procedimentos Cirúrgicos Ambulatórios/métodos , Hérnia Inguinal/cirurgia , Herniorrafia/métodos , Pacientes Ambulatoriais , Robótica/métodos , Adolescente , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Osteopontin acts thru myeloid zinc finger-1 and transforming growth factor-ß to drive the adoption of a cancer-associated fibroblast phenotype by local mesenchymal stem cells. Cancer-associated fibroblasts increase cancer cell stemness. METHODS: Mesenchymal stem cells were exposed to osteopontin or were cocultured with MB231 human breast cancer cells (high osteopontin producer) in the presence or absence of aptamer (inactivates extracellular osteopontin). Myeloid zinc finger-1 phosphorylation sites were identified, and phosphomutants of T134 (SCAN domain) and S453 (zinc finger DNA binding domain) were constructed. Transforming growth factor-ß F and cancer-associated fibroblast markers (smooth muscle actin, vimentin, and tenascin-c) were measured in mesenchymal stem cells. In MB231, stemness markers Sox2, Nanog, and Oct4 were measured. RESULTS: Mesenchymal stem cells plus osteopontin increased transforming growth factor-ß and cancer-associated fibroblast markers (P < .05 vs mesenchymal stem cells alone); this was abolished by aptamer inactivation of osteopontin. In mesenchymal stem cells transfected with phosphoresistant myeloid zinc finger-1, osteopontin did not increase cancer-associated fibroblast markers or transforming growth factor-ß. In contrast, phosphomimetic myeloid zinc finger-1 increased cancer-associated fibroblast markers and transforming growth factor-ß (P < .05 vs mesenchymal stem cells alone). In mesenchymal stem cells plus MB231, MB231 stemness markers were increased (P < .05 vs MB231 alone). In MB231 plus mesenchymal stem cells expressing phosphoresistant myeloid zinc finger-1, MB231 stemness markers were not increased in comparison with MB231 plus mesenchymal stem cells. CONCLUSION: Myeloid zinc finger-1 phosphorylation in mesenchymal stem cells drives the osteopontin-mediated cancer-associated fibroblast phenotype, which then increases the cancer cell stemness profile.
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Neoplasias da Mama/genética , Fibroblastos Associados a Câncer/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Regulação da Expressão Gênica , Fatores de Transcrição Kruppel-Like/genética , Osteopontina/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Fibroblastos Associados a Câncer/citologia , Linhagem Celular Tumoral , Técnicas de Cocultura , Feminino , Humanos , Células-Tronco Mesenquimais , Sensibilidade e Especificidade , Fator de Crescimento Transformador beta1/metabolismo , Microambiente TumoralRESUMO
BACKGROUND: The categorical general surgery (GS) applicant pool and trainees have evolved. The purpose of this study is to profile contemporary applicants and subsequent matriculates of GS residencies. STUDY DESIGN: This study is a retrospective review of GS applicant and PGY1 trainee data which were obtained from ERAS, NRMP, and AAMC for the years 2013-2016. Univariate statistics were used to compare matched GS trainees other trainees in other specialties. RESULTS: In 2016â¯GS was among the top 5 most competitive residencies as measured by mean applications/applicant. In 2013, 2415 applicants applied for 1185 spots resulting in 99.6% fill. The 2014 PGY1 class exhibited: mean Step 1232 vs. 213 and Step 2245 vs. 226 when comparing matched to unmatched. The mean number of abstracts/publications and %AOA were 4.4 v. 2.7, and 4.4% vs.2.7% respectively. Surgical subspecialty trainees had significantly higher Step 1 and 2 scores, publications, and %AOA (pâ¯<â¯.0001). CONCLUSION: General surgery is an increasingly competitive specialty. PGY1 trainees compare well with their CIM and Obstetrics peers, but lag behind their surgical subspecialty colleagues.
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Escolha da Profissão , Cirurgia Geral/educação , Internato e Residência , Bases de Dados Factuais , Escolaridade , Feminino , Humanos , Masculino , Estudos Retrospectivos , Estados Unidos , Adulto JovemRESUMO
BACKGROUND: Cancer cells metastasize to the bone marrow to create the premetastatic niche. Cancer stemness (expression of stem cell characteristics) is regulated by the tumor microenvironment and associated with self-renewal and poor clinical outcomes. Osteopontin induces mesenchymal stem cells in the tumor microenvironment to adopt a cancer-associated fibroblast phenotype to potentiate cancer growth and metastasis. The mechanisms by which cancer cells and tumor microenvironment regulate stemness in the bone marrow premetastatic niche is unknown. METHODS: Human breast cancer cell lines, MDA-MB-231 and MCF-7 were used in an orthotopic murine xenograft model. NOD-scid mice were implanted with 2 × 106 tumor cells in the presence and absence of human mesenchymal stem cells-green fluorescent protein cells and/or osteopontin aptamer, which blocks and inactivates extracellular osteopontin, or mutant aptamer (osteopontin mutant aptamer). In select instances, MCF-7 cells transfected to express osteopontin were coimplanted instead of MCF-7. Stemness markers (Nanog, Oct4, Sox2) in the tumor cells and cancer-associated fibroblast (α-smooth muscle actin, Vimentin) markers in the mesenchymal stem cells were measured in femoral bone marrow via real-time polymerase chain reaction. Cell number was determined by titrating cell number to Ct value in vitro. RESULTS: Tumor cells and mesenchymal stem cells migrate from the primary tumor site to the bone marrow. Migration of mesenchymal stem cells is osteopontin dependent. In both MDA-MB-231 and MCF-7 cell lines, levels of both cancer-associated fibroblast and stemness markers were 3 to 4 times greater under conditions wherein mesenchymal stem cells were present with osteopontin. Inactivation of extracellular osteopontin with an aptamer decreased migration of mesenchymal stem cells and expression of both cancer-associated fibroblast and stemness markers. Cancer cells exhibited a significantly increased stem cell profile in the presence of cancer-associated fibroblast in the bone marrow. In the presence and absence of osteopontin, Sox2 knockdown abolished expression of both Nanog and Oct4. CONCLUSION: We conclude that osteopontin-dependent migration of cancer-associated fibroblast is required for increased cancer cell stemness in the bone marrow premetastatic niche.
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Medula Óssea/patologia , Neoplasias da Mama/patologia , Fibroblastos Associados a Câncer/fisiologia , Células-Tronco Mesenquimais/fisiologia , Micrometástase de Neoplasia , Osteopontina/fisiologia , Animais , Movimento Celular , Feminino , Humanos , Células MCF-7 , Neoplasias Mamárias Experimentais , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Transplante de Neoplasias , Células-Tronco NeoplásicasRESUMO
BACKGROUND: We hypothesized that the increasing body mass index of the population has affected general surgery malpractice claims. METHODS: We queried the Physician Insurers Association of America database from 1990 to 1999 (ie, period 1) and 2000 to 2009 (ie, period 2) for claims associated with obesity and morbid obesity. We analyzed the error involved, injury severity, procedure, and outcome. RESULTS: Five hundred seventy-five claims were identified. The percentage of paid claims did not differ by body mass index. Improper performance was the most common alleged error, gastric bypass was the most common procedure, and death was the most common injury. For obesity claims, the case was more likely to be settled in period 1 and withdrawn/dismissed in period 2 (P < .001). The number of morbid obesity claims rose from 9 in period 1 to 249 in period 2. CONCLUSIONS: The significant rise in morbid obesity claims between periods is likely caused by the substantial increase in the number of bariatric procedures performed.
Assuntos
Derivação Gástrica/mortalidade , Imperícia/economia , Obesidade Mórbida/cirurgia , Obesidade/cirurgia , Índice de Massa Corporal , Distribuição de Qui-Quadrado , Feminino , Humanos , Seguro de Responsabilidade Civil/economia , Masculino , Obesidade/mortalidade , Obesidade Mórbida/mortalidade , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: The increasing prevalence of obesity has altered the practice of medicine and surgery, with the emergence of new operations and medications. We hypothesized that the landscape of medical malpractice claims has also changed. METHODS: We queried the Physician Insurers Association of American database for 1990 through 1999 and 2000 through 2009 for cases corresponding to International Classification of Diseases, 9th edition, codes for obesity. We extracted adjudicatory outcome, closed and paid claims data, indemnity payments, primary alleged error codes, National Association of Insurance Commissioners severity of injury class, procedural codes, and medical specialty data. RESULTS: A total of 411 obesity claims were filed from 1990 to 1999 and 1,591 obesity claims were filed from 2000 to 2009. General surgery was the specialty with the greatest number of obesity claims from 1990 to 1999 and was second to family practice for 2000 to 2009. Although the percentage of paid general surgery obesity claims has decreased significantly from 69% in 1990-1999 to 36% in 2000-2009, the mean indemnity payments have increased substantially ($94,000 to $368,000). CONCLUSION: Recently, the percentage of paid general surgery obesity claims has significantly decreased; however, individual and total indemnity payments have increased. Obesity continues to impact general surgery malpractice substantially. Efforts to manage this component of physician and hospital practices must continue.
Assuntos
Fármacos Antiobesidade/efeitos adversos , Cirurgia Bariátrica/efeitos adversos , Imperícia , Obesidade/tratamento farmacológico , Obesidade/cirurgia , Humanos , Seguro de Responsabilidade Civil , Obesidade/epidemiologia , Fatores de TempoRESUMO
BACKGROUND: In the current environment, pressure is ever increasing to maximize financial performance in surgery departments. Factors such as physician extenders, billing and collection, payor mix, contracting, incentives from the Centers for Medicare and Medicaid Services, and administrative incentives may greatly influence financial performance. However, despite a plethora of information from the University HealthSystem Consortium and the Association of American Medical Colleges, best-practice information for business infrastructure is lacking. To obtain a sampling of current practices, we conducted a survey of departments of surgery. METHODS: An anonymous 30-question survey addressing demographics, productivity, revenue and expense profile, payor mix, physician extender and staff personnel, billing and collections methodology, and financial performance was distributed among members of the Society of Surgical Chairs via SurveyMonkey. This was approved by the Loyola Institutional Research Board. Multivariate linear regression analyses and t tests/rank-sum tests were performed, as appropriate. Data are presented as mean ± SEM. RESULTS: A total of 25 (19%) departments responded; 14 were integrated with the hospital/health system, and 11 were integrated with the medical school. In 60% (n = 15), the main hospital had 500 to 1,000 beds; 48% (n = 12) had >4 hospitals in their system. For FY10, MD clinical full-time equivalents (FTEs) were 49 ± 10; total work relative value units (wRVUs) were 320 ± 8 k; and total billed cases were 43 ± 16 k. A total of 23 of 25 used physician-extenders with an average of 18 ± 5 per department and in 22 of 23, the physician extenders billed. On average, there were 18 ± 6 clinical-support staff, 25 ± 11 front-office staff, and 13 ± 3 back-office support staff FTEs. Among these FTEs, there were 16 ± 5 devoted to business operations (billing, coding, denial/claims management, financial oversight). Collections/wRVUs were $60 ± 3 (range, 39-80). Regression modeling demonstrated that total wRVUs were determined by the number of MD FTEs (P = .01), number of physician extenders (P = .01), number of front-office staff (P = .01), number of back-office staff (P = .02), and number of total business staff (P = .01). Collections/wRVUs were predicted by number of hospitals (P = .04), number of MD FTEs (P = .03), number of physician extenders (P = .01), and number of cases/total business staff (P = .02). Interestingly, wRVUs/MD was predicted by number of MD FTEs (P = .01) but were not greatly impacted by numbers of clinical or business support staff. In 4 of 25, the billing and coding staff were incentivized and had a Collections/wRVU = 64 ± 5 whereas nonincentivized staff had collections/wRVU = 59 ± 3. (P = NS) Also, %Accounts receivable >90 days (15% vs 25%) were not substantially different. Only 48% (12/25) have departments have recouped Centers for Medicare and Medicaid dollars for Physician Quality Reporting Initiative, Meaningful Use, Patient-Centered Medical Homes, or other Accountable Care-like programs. One-half (13) of the departments had both an inpatient and outpatient electronic medical record. Finally, on a scale of 1-10 (10 = highest), the average level of satisfaction with billing and collections processes was 6. CONCLUSION: Our results indicate that the physician extender, clinical support staff, and business staff environment can impact surgeon productivity, and there is opportunity for improvement. Determining best practices for ratios of support staff/MD and optimizing the role of electronic medical record in workflow and billing/collections are critical in the current environment. Our pilot study requires extension across more institutions for validation.