Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 127
Filtrar
1.
Ann Surg ; 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38814074

RESUMO

OBJECTIVE: An expert panel made recommendations to optimize surgical education and training based on the effects of contemporary challenges. BACKGROUND: The inaugural Blue Ribbon Committee (BRC I) proposed sweeping recommendations for surgical education and training in 2004. In light of those findings, a second BRC (BRC II) was convened to make recommendations to optimize surgical training considering the current landscape in medical education. METHODS: BRC II was a panel of 67 experts selected on the basis of experience and leadership in surgical education and training. It was organized into subcommittees which met virtually over the course of a year. They developed recommendations, along with the Steering Committee, based on areas of focus and then presented them to the entire BRC II. The Delphi Method was chosen to obtain consensus, defined as>80% agreement amongst the panel. Cronbach alpha was computed to assess the internal consistency of three Delphi rounds. RESULTS: Of 50 recommendations, 31 obtained consensus in the following aspects of surgical training (# consensus recommendation /# proposed): Workforce (1/5), Medical Student Education (3/8), Work Life Integration (4/6), Resident Education (5/7), Goals, Structure and Financing of Training (5/8), Education Support and Faculty Development (5/6), Research Training (7/9), and Educational Technology and Assessment (1/1). The internal consistency was good in Rounds 1 and 2 and acceptable in Round 3. CONCLUSIONS: BRC II used the Delphi approach to identify and recommend 31 priorities for surgical education in 2024. We advise establishing a multidisciplinary surgical educational group to oversee, monitor and facilitate implementation of these recommendations.

2.
JAMA Surg ; 159(2): 228-229, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38117492

RESUMO

This cross-sectional study assesses the level of adoption of 5 new tools that promote high quality and transparency in surgical research.


Assuntos
Publicações Periódicas como Assunto , Humanos , Editoração , Revisão da Pesquisa por Pares
3.
Clin Cancer Res ; 30(4): 729-740, 2024 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-38109213

RESUMO

PURPOSE: The neutralizing peptibody trebananib prevents angiopoietin-1 and angiopoietin-2 from binding with Tie2 receptors, inhibiting angiogenesis and proliferation. Trebananib was combined with paclitaxel±trastuzumab in the I-SPY2 breast cancer trial. PATIENTS AND METHODS: I-SPY2, a phase II neoadjuvant trial, adaptively randomizes patients with high-risk, early-stage breast cancer to one of several experimental therapies or control based on receptor subtypes as defined by hormone receptor (HR) and HER2 status and MammaPrint risk (MP1, MP2). The primary endpoint is pathologic complete response (pCR). A therapy "graduates" if/when it achieves 85% Bayesian probability of success in a phase III trial within a given subtype. Patients received weekly paclitaxel (plus trastuzumab if HER2-positive) without (control) or with weekly intravenous trebananib, followed by doxorubicin/cyclophosphamide and surgery. Pathway-specific biomarkers were assessed for response prediction. RESULTS: There were 134 participants randomized to trebananib and 133 to control. Although trebananib did not graduate in any signature [phase III probabilities: Hazard ratio (HR)-negative (78%), HR-negative/HER2-positive (74%), HR-negative/HER2-negative (77%), and MP2 (79%)], it demonstrated high probability of superior pCR rates over control (92%-99%) among these subtypes. Trebananib improved 3-year event-free survival (HR 0.67), with no significant increase in adverse events. Activation levels of the Tie2 receptor and downstream signaling partners predicted trebananib response in HER2-positive disease; high expression of a CD8 T-cell gene signature predicted response in HR-negative/HER2-negative disease. CONCLUSIONS: The angiopoietin (Ang)/Tie2 axis inhibitor trebananib combined with standard neoadjuvant therapy increased estimated pCR rates across HR-negative and MP2 subtypes, with probabilities of superiority >90%. Further study of Ang/Tie2 receptor axis inhibitors in validated, biomarker-predicted sensitive subtypes is warranted.


Assuntos
Neoplasias da Mama , Proteínas Recombinantes de Fusão , Feminino , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Teorema de Bayes , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Terapia Neoadjuvante , Paclitaxel/efeitos adversos , Receptor ErbB-2/metabolismo , Receptor TIE-2 , Trastuzumab/efeitos adversos
4.
Cell Rep Med ; 4(12): 101312, 2023 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-38086377

RESUMO

Molecular subtyping of breast cancer is based mostly on HR/HER2 and gene expression-based immune, DNA repair deficiency, and luminal signatures. We extend this description via functional protein pathway activation mapping using pre-treatment, quantitative expression data from 139 proteins/phosphoproteins from 736 patients across 8 treatment arms of the I-SPY 2 Trial (ClinicalTrials.gov: NCT01042379). We identify predictive fit-for-purpose, mechanism-of-action-based signatures and individual predictive protein biomarker candidates by evaluating associations with pathologic complete response. Elevated levels of cyclin D1, estrogen receptor alpha, and androgen receptor S650 associate with non-response and are biomarkers for global resistance. We uncover protein/phosphoprotein-based signatures that can be utilized both for molecularly rationalized therapeutic selection and for response prediction. We introduce a dichotomous HER2 activation response predictive signature for stratifying triple-negative breast cancer patients to either HER2 or immune checkpoint therapy response as a model for how protein activation signatures provide a different lens to view the molecular landscape of breast cancer and synergize with transcriptomic-defined signatures.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Neoplasias de Mama Triplo Negativas , Humanos , Resistencia a Medicamentos Antineoplásicos/genética , Terapia Neoadjuvante , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Biomarcadores , Perfilação da Expressão Gênica
5.
Ann Surg Open ; 4(1): e260, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37600898

RESUMO

Background: Surgeon productivity is measured in relative value units (RVUs). The feasibility of attaining RVU productivity targets requires surgeons to have enough allocated block time to generate RVUs. However, it is unknown how much block time is required for surgeons to attain specific RVU targets. We aimed to estimate the effect of surgeon and practice environment characteristics (SPECs) on block time needed to attain fixed RVU targets. Methods: We computationally simulated individual surgeons' annual caseloads under a variety of SPECs in the following way. First, empirical case data were sampled from ACS NSQIP in accordance with surgeon specialty, case-mix complexity, and RVU target. Surgeons' operating schedules were then constructed according to the block length, turnover time, and scheduling flexibility of the practice environment. These 6 SPECs were concurrently varied over their ranges for a 6-way sensitivity analysis. Results: Annual operating schedules for 60,000,000 surgeons were simulated. The number of blocks required to attain RVU targets varied significantly with surgeon specialty and increased with increased case-mix complexity, increased turnover time, and decreased scheduling flexibility. Intraspecialty variation in block requirement with variation in environmental characteristics exceeded interspecialty variation with fixed environmental characteristics. Multivariate linear models predicted block utilization across surgical specialties with consideration for the stated factors. An online tool is shared with which to apply these results to one's particular practice. Conclusions: Block time required to attain RVU targets varies widely with SPECs; intraspecialty variation exceeds interspecialty variation. The feasibility of attaining RVU targets requires alignment between targets and allocated operating time with consideration for surgical specialty and other practice conditions.

6.
medRxiv ; 2023 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-37205325

RESUMO

Open science practices are research tools used to improve research quality and transparency. These practices have been used by researchers in various medical fields, though the usage of these practices in the surgical research ecosystem has not been quantified. In this work, we studied the use of open science practices in general surgery journals. Eight of the highest-ranked general surgery journals by SJR2 were chosen and their author guidelines were reviewed. From each journal, 30 articles published between January 1, 2019 and August 11, 2021 were randomly chosen and analyzed. Five open science practices were measured (preprint publication prior to peer-reviewed publication, use of Equator guidelines, study protocol preregistration prior to peer-reviewed publication, published peer review, and public accessibility of data, methods, and/or code). Across all 240 articles, 82 (34%) used one or more open science practices. Articles in the International Journal of Surgery showed greatest use of open science practices, with a mean of 1.6 open science practices compared to 0.36 across the other journals (p<.001). Adoption of open science practices in surgical research remains low, and further work is needed to increase utilization of these tools.

7.
Ann Surg ; 277(5): e1006-e1017, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35796435

RESUMO

OBJECTIVE: To propose a framework for quantification of surgical team familiarity. BACKGROUND: Operating room (OR) teamwork quality is associated with familiarity among team members and their individual specialization. We describe novel measures of OR team familiarity and specialty experience. METHODS: Surgeon-scrub (SS) and surgeon-circulator (SC) teaming scores, defined as the pair's proportion of interactions relative to the surgeon's total cases in the preceding 6 months were calculated between 2017 and 2021 at an academic medical center. Nurse service-line (SL) experience scores were defined as the proportion of a nurse's cases performed within the given specialty. SS, SC, and nurse-SL scores were analyzed by specialty, case urgency, robotic approach, and surgeon academic rank. Two-sample Kolmogorov-Smirnov tests were used to determine heterogeneity between distributions. RESULTS: A total of 37,364 operations involving 150 attending surgeons and 222 nurses were analyzed. Median SS and SC scores were 0.08 (interquartile range: 0.03-0.19) and 0.06 (interquartile range: 0.03-0.13), respectively. Higher margin SLs, senior faculty rank, elective, and robotic cases were associated with greater SS, SC, and nurse-SL scores ( P <0.001). CONCLUSIONS: These novel measures of teaming and specialization illustrate the low levels of OR team familiarity and objectively highlight differences that necessitate a deliberate evaluation of current OR scheduling practices.


Assuntos
Medicina , Robótica , Cirurgiões , Humanos , Equipe de Assistência ao Paciente , Centros Médicos Acadêmicos , Especialização
8.
Ann Surg ; 277(1): 66-72, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35997268

RESUMO

OBJECTIVE: The aim of this review was to review the ethical and multidisciplinary clinical challenges facing trauma surgeons when resuscitating patients presenting with penetrating brain injury (PBI) and multicavitary trauma. BACKGROUND: While there is a significant gap in the literature on managing PBI in patients presenting with multisystem trauma, recent data demonstrate that resuscitation and prognostic features for such patients remains poorly described, with trauma guidelines out of date in this field. METHODS: We reviewed a combination of recent multidisciplinary evidence-informed guidelines for PBI and coupled this with expert opinion from trauma, neurosurgery, neurocritical care, pediatric and transplant surgery, surgical ethics and importantly our community partners. RESULTS: Traditional prognostic signs utilized in traumatic brain injury may not be applicable to PBI with a multidisciplinary team approach suggested on a case-by-case basis. Even with no role for neurosurgical intervention, neurocritical care, and neurointerventional support may be warranted, in parallel to multicavitary operative intervention. Special considerations should be afforded for pediatric PBI. Ethical considerations center on providing the patient with the best chance of survival. Consideration of organ donation should be considered as part of the continuum of patient, proxy and family-centric support and care. Community input is crucial in guiding decision making or protocol establishment on an institutional level. CONCLUSIONS: Support of the patient after multicavitary PBI can be complex and is best addressed in a multidisciplinary fashion with extensive community involvement.


Assuntos
Lesões Encefálicas Traumáticas , Traumatismos Cranianos Penetrantes , Obtenção de Tecidos e Órgãos , Humanos , Criança , Ressuscitação/métodos , Procedimentos Neurocirúrgicos
9.
J Am Coll Surg ; 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36472390

RESUMO

BACKGROUND: This study assessed the national impact of the COVID-19 pandemic on the education of medical students assigned to surgery clerkship rotations, as reported by surgery clerkship directors(CDs). STUDY DESIGN: In the spring of 2020 and 2021, the authors surveyed 164 CDs from 144 LCME-accredited US medical schools regarding their views of the pandemic's impact on the surgery clerkship curriculum, students' experiences, outcomes, and institutional responses. RESULTS: Overall survey response rates, calculated as no. respondents/no. surveyed were 44.5%(73/164) and 50.6%(83/164) for the spring 2020 and 2021 surveys, respectively. Nearly all CDs(>95%) pivoted to virtual platforms and solutions. Most returned to some form of in-person learning by winter 2020, and pre-pandemic status by spring 2021(46%, 38/83). Students' progression to the next year was delayed by 12%(9/73), and preparation was negatively impacted by 45%(37/83). Despite these data, CDs perceived students' interest in surgical careers was not significantly affected(89% vs. 77.0%, p=0.09). Over the one-year study, the proportion of CDs reporting a severe negative impact on the curriculum dropped significantly(p<0.0001) for most parameters assessed except summative evaluations(40.3% vs. 45.7%,p=0.53). CDs(n=83) also noted the pandemic's positive impact with respect to virtual patient encounters(21.7%), didactics(16.9%), student test performance(16.9%), continuous personal learning(14.5%), engagement in the clerkship(9.6%) and student interest in surgery as a career(7.2%). CONCLUSION: During the pandemic, the severe negative impact on student educational programs lessened and novel virtual curricular solutions emerged. Student interest in surgery as a career was sustained. Measures of student competency and effectiveness of new curriculum, including telehealth, remain areas for future investigation.

10.
NPJ Breast Cancer ; 8(1): 128, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36456573

RESUMO

HSP90 inhibitors destabilize oncoproteins associated with cell cycle, angiogenesis, RAS-MAPK activity, histone modification, kinases and growth factors. We evaluated the HSP90-inhibitor ganetespib in combination with standard chemotherapy in patients with high-risk early-stage breast cancer. I-SPY2 is a multicenter, phase II adaptively randomized neoadjuvant (NAC) clinical trial enrolling patients with stage II-III breast cancer with tumors 2.5 cm or larger on the basis of hormone receptors (HR), HER2 and Mammaprint status. Multiple novel investigational agents plus standard chemotherapy are evaluated in parallel for the primary endpoint of pathologic complete response (pCR). Patients with HER2-negative breast cancer were eligible for randomization to ganetespib from October 2014 to October 2015. Of 233 women included in the final analysis, 140 were randomized to the standard NAC control; 93 were randomized to receive 150 mg/m2 ganetespib every 3 weeks with weekly paclitaxel over 12 weeks, followed by AC. Arms were balanced for hormone receptor status (51-52% HR-positive). Ganetespib did not graduate in any of the biomarker signatures studied before reaching maximum enrollment. Final estimated pCR rates were 26% vs. 18% HER2-negative, 38% vs. 22% HR-negative/HER2-negative, and 15% vs. 14% HR-positive/HER2-negative for ganetespib vs control, respectively. The predicted probability of success in phase 3 testing was 47% HER2-negative, 72% HR-negative/HER2-negative, and 19% HR-positive/HER2-negative. Ganetespib added to standard therapy is unlikely to yield substantially higher pCR rates in HER2-negative breast cancer compared to standard NAC, and neither HSP90 pathway nor replicative stress expression markers predicted response. HSP90 inhibitors remain of limited clinical interest in breast cancer, potentially in other clinical settings such as HER2-positive disease or in combination with anti-PD1 neoadjuvant chemotherapy in triple negative breast cancer.Trial registration: www.clinicaltrials.gov/ct2/show/NCT01042379.

11.
J Am Coll Surg ; 235(2): 195-209, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35839394

RESUMO

BACKGROUND: A previous survey documented the severe disruption of the coronavirus disease 2019 pandemic on surgical education and trainee well-being during the initial surge and systemic lockdowns. Herein, we report the results of a follow-up survey inclusive of the 2020 to 2021 academic year. STUDY DESIGN: A survey was distributed to education leaders across all surgical specialties in summer 2021. We compared the proportion of participants reporting severe disruption in key areas with those of the spring 2020 survey. Aggregated differences by year were assessed using chi-square analysis. RESULTS: In 2021, severe disruption of education programs was reported by 14% compared with 32% in 2020 (p < 0.0001). Severe reductions in nonemergency surgery were reported by 38% compared with 87% of respondents in 2020. Severe disruption of expected progression of surgical trainee autonomy by rank also significantly decreased to 5% to 8% in 2021 from 15% to 23% in 2020 among respondent programs (p < 0.001). In 2021 clinical remediation was reported for postgraduate year 1 to 2 and postgraduate year 3 to 4, typically through revised rotations (19% and 26%) and additional use of simulation (20% and 19%) maintaining trainee promotion and job placement. In 2021, surgical trainees' physical safety and health were reported as less severely impacted compared with 2020; however, negative effects of isolation (77%), burnout (75%), and the severe impact on emotional well-being (17%) were prevalent. CONCLUSIONS: One year after the initial coronavirus disease 2019 outbreak, clinical training and surgical trainee health were less negatively impacted. Disruption of emotional well-being remained high. Future needs include better objective measures of clinical competence beyond case numbers and the implementation of novel programs to promote surgical trainee health and well-being.


Assuntos
COVID-19 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Controle de Doenças Transmissíveis , Educação de Pós-Graduação em Medicina/métodos , Seguimentos , Humanos , Pandemias/prevenção & controle , Inquéritos e Questionários
12.
Cancer Cell ; 40(6): 609-623.e6, 2022 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-35623341

RESUMO

Using pre-treatment gene expression, protein/phosphoprotein, and clinical data from the I-SPY2 neoadjuvant platform trial (NCT01042379), we create alternative breast cancer subtypes incorporating tumor biology beyond clinical hormone receptor (HR) and human epidermal growth factor receptor-2 (HER2) status to better predict drug responses. We assess the predictive performance of mechanism-of-action biomarkers from ∼990 patients treated with 10 regimens targeting diverse biology. We explore >11 subtyping schemas and identify treatment-subtype pairs maximizing the pathologic complete response (pCR) rate over the population. The best performing schemas incorporate Immune, DNA repair, and HER2/Luminal phenotypes. Subsequent treatment allocation increases the overall pCR rate to 63% from 51% using HR/HER2-based treatment selection. pCR gains from reclassification and improved patient selection are highest in HR+ subsets (>15%). As new treatments are introduced, the subtyping schema determines the minimum response needed to show efficacy. This data platform provides an unprecedented resource and supports the usage of response-based subtypes to guide future treatment prioritization.


Assuntos
Neoplasias da Mama , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Feminino , Humanos , Terapia Neoadjuvante , Receptor ErbB-2/genética , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo
13.
Am J Surg ; 223(2): 395-403, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34272062

RESUMO

BACKGROUND: The time course and longitudinal impact of the COVID -19 pandemic on surgical education(SE) and learner well-being (LWB)is unknown. MATERIAL AND METHODS: Check-in surveys were distributed to Surgery Program Directors and Department Chairs, including general surgery and surgical specialties, in the summer and winter of 2020 and compared to a survey from spring 2020. Statistical associations for items with self-reported ACGME Stage and the survey period were assessed using categorical analysis. RESULTS: Stage 3 institutions were reported in spring (30%), summer (4%) [p < 0.0001] and increased in the winter (18%). Severe disruption (SD) was stage dependent (Stage 3; 45% (83/184) vs. Stages 1 and 2; 26% (206/801)[p < 0.0001]). This lessened in the winter (23%) vs. spring (32%) p = 0.02. LWB severe disruption was similar in spring 27%, summer 22%, winter 25% and was associated with Stage 3. CONCLUSIONS: Steps taken during the pandemic reduced SD but did not improve LWB. Systemic efforts are needed to protect learners and combat isolation pervasive in a pandemic.


Assuntos
COVID-19/epidemiologia , Controle de Doenças Transmissíveis/normas , Educação Médica/estatística & dados numéricos , Pandemias/prevenção & controle , Especialidades Cirúrgicas/educação , COVID-19/prevenção & controle , COVID-19/psicologia , COVID-19/transmissão , Educação Médica/organização & administração , Educação Médica/normas , Humanos , Aprendizagem , Especialidades Cirúrgicas/estatística & dados numéricos , Inquéritos e Questionários/estatística & dados numéricos , Estados Unidos/epidemiologia
14.
Nat Commun ; 12(1): 6428, 2021 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-34741023

RESUMO

HER2-targeted therapy dramatically improves outcomes in early breast cancer. Here we report the results of two HER2-targeted combinations in the neoadjuvant I-SPY2 phase 2 adaptive platform trial for early breast cancer at high risk of recurrence: ado-trastuzumab emtansine plus pertuzumab (T-DM1/P) and paclitaxel, trastuzumab and pertuzumab (THP). Eligible women have >2.5 cm clinical stage II/III HER2+ breast cancer, adaptively randomized to T-DM1/P, THP, or a common control arm of paclitaxel/trastuzumab (TH), followed by doxorubicin/cyclophosphamide, then surgery. Both T-DM1/P and THP arms 'graduate' in all subtypes: predicted pCR rates are 63%, 72% and 33% for T-DM1/P (n = 52), THP (n = 45) and TH (n = 31) respectively. Toxicity burden is similar between arms. Degree of HER2 pathway signaling and phosphorylation in pretreatment biopsy specimens are associated with response to both T-DM1/P and THP and can further identify highly responsive HER2+ tumors to HER2-directed therapy. This may help identify patients who can safely de-escalate cytotoxic chemotherapy without compromising excellent outcome.


Assuntos
Ado-Trastuzumab Emtansina/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Terapia Neoadjuvante/métodos , Adulto , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Biomarcadores Tumorais , Humanos , Maitansina/uso terapêutico , Pessoa de Meia-Idade , Paclitaxel/uso terapêutico , Receptor ErbB-2/uso terapêutico , Trastuzumab/uso terapêutico
15.
NPJ Breast Cancer ; 7(1): 131, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34611148

RESUMO

I-SPY2 is an adaptively randomized phase 2 clinical trial evaluating novel agents in combination with standard-of-care paclitaxel followed by doxorubicin and cyclophosphamide in the neoadjuvant treatment of breast cancer. Ganitumab is a monoclonal antibody designed to bind and inhibit function of the type I insulin-like growth factor receptor (IGF-1R). Ganitumab was tested in combination with metformin and paclitaxel (PGM) followed by AC compared to standard-of-care alone. While pathologic complete response (pCR) rates were numerically higher in the PGM treatment arm for hormone receptor-negative, HER2-negative breast cancer (32% versus 21%), this small increase did not meet I-SPY's prespecified threshold for graduation. PGM was associated with increased hyperglycemia and elevated hemoglobin A1c (HbA1c), despite the use of metformin in combination with ganitumab. We evaluated several putative predictive biomarkers of ganitumab response (e.g., IGF-1 ligand score, IGF-1R signature, IGFBP5 expression, baseline HbA1c). None were specific predictors of response to PGM, although several signatures were associated with pCR in both arms. Any further development of anti-IGF-1R therapy will require better control of anti-IGF-1R drug-induced hyperglycemia and the development of more predictive biomarkers.

16.
JAMA Oncol ; 7(11): 1654-1663, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34529000

RESUMO

IMPORTANCE: Residual cancer burden (RCB) distributions may improve the interpretation of efficacy in neoadjuvant breast cancer trials. OBJECTIVE: To compare RCB distributions between randomized control and investigational treatments within subtypes of breast cancer and explore the relationship with survival. DESIGN, SETTING, AND PARTICIPANTS: The I-SPY2 is a multicenter, platform adaptive, randomized clinical trial in the US that compares, by subtype, investigational agents in combination with chemotherapy vs chemotherapy alone in adult women with stage 2/3 breast cancer at high risk of early recurrence. Investigational treatments graduated in a prespecified subtype if there was 85% or greater predicted probability of higher rate of pathologic complete response (pCR) in a confirmatory, 300-patient, 1:1 randomized, neoadjuvant trial in that subtype. Evaluation of a secondary end point was reported from the 10 investigational agents tested in the I-SPY2 trial from March 200 through 2016, and analyzed as of September 9, 2020. The analysis plan included modeling of RCB within subtypes defined by hormone receptor (HR) and ERBB2 status and compared control treatments with investigational treatments that graduated and those that did not graduate. INTERVENTIONS: Neoadjuvant paclitaxel plus/minus 1 of several investigational agents for 12 weeks, then 12 weeks of cyclophosphamide/doxorubicin chemotherapy followed by surgery. MAIN OUTCOMES AND MEASURES: Residual cancer burden (pathological measure of residual disease) and event-free survival (EFS). RESULTS: A total of 938 women (mean [SD] age, 49 [11] years; 66 [7%] Asian, 103 [11%] Black, and 750 [80%] White individuals) from the first 10 investigational agents were included, with a median follow-up of 52 months (IQR, 29 months). Event-free survival worsened significantly per unit of RCB in every subtype of breast cancer (HR-positive/ERBB2-negative: hazard ratio [HZR], 1.75; 95% CI, 1.45-2.16; HR-positive/ERBB2-positive: HZR, 1.55; 95% CI, 1.18-2.05; HR-negative/ERBB2-positive: HZR, 2.39; 95% CI, 1.64-3.49; HR-negative/ERBB2-negative: HZR, 1.99; 95% CI, 1.71-2.31). Prognostic information from RCB was similar from treatments that graduated (HZR, 2.00; 95% CI, 1.57-2.55; 254 [27%]), did not graduate (HZR, 1.87; 95% CI, 1.61-2.17; 486 [52%]), or were control (HZR, 1.79; 95% CI, 1.42-2.26; 198 [21%]). Investigational treatments significantly lowered RCB in HR-negative/ERBB2-negative (graduated and nongraduated treatments) and ERBB2-positive subtypes (graduated treatments), with improved EFS (HZR, 0.61; 95% CI, 0.41-0.93) in the exploratory analysis. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, the prognostic significance of RCB was consistent regardless of subtype and treatment. Effective neoadjuvant treatments shifted the distribution of RCB in addition to increasing pCR rate and appeared to improve EFS. Using a standardized quantitative method to measure response advances the interpretation of efficacy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01042379.


Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Neoplasia Residual , Prognóstico , Intervalo Livre de Progressão , Receptor ErbB-2/análise
17.
J Am Coll Surg ; 233(6): 722-729, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34438078

RESUMO

BACKGROUND: Program directors use US Medical Licensing Exam (USMLE) scores as criteria for ranking applicants. First-time pass rates of the American Board of Surgery (ABS) Qualifying (QE) and Certifying (CE) Examinations have become important measures of residency program quality. USMLE Step 1 will become pass/fail in 2022. STUDY DESIGN: American Board of Surgery QE and CE success rates were assessed considering multiple characteristics of highly ranked (top 20) applicants to 22 general surgery programs in 2011. Chi-square, t-test, Wilcoxon Rank sum, linear and logistic regression were used, as appropriate. RESULTS: The QE and CE first attempt pass rates were 96% (235/244) and 86% (190/221), respectively. QE/CE success was not significantly associated with sex, race, research experience, or publications. Alpha Omega Alpha (AΩA) status was associated with success on the index CE (98% vs 83%; p = 0.008). Step 1 and Step 2 Clinical Knowledge (CK) scores of surgeons who passed QE on their first attempt were higher than scores of those who failed (Step 1: 233 vs 218; p = 0.016); (Step 2CK: 244 vs 228, p = 0.009). For every 10-point increase in Step 1 and 2CK scores, the odds of passing CE on the first attempt increased 1.5 times (95% CI 1.12, 2.0; p = 0.006) and 1.5 times (95% CI 1.11, 2.02, p = 0.008), respectively. For every 10-point increase in Steps 1 and 2CK scores, the odds of passing the QE on the first attempt increased 1.85 times (95% CI 1.11, 3.09; p = 0.018) and 1.86 times (95% CI 1.14, 3.06, p = 0.013), respectively. CONCLUSIONS: USMLE Step 1 and Step 2 CK examination scores correlate with American Board of Surgery QE and CE performance and success. The USMLE decision to transition Step 1 to a pass/fail examination will require program directors to identify other factors that predict ABS performance for ranking applicants.


Assuntos
Avaliação Educacional/estatística & dados numéricos , Licenciamento em Medicina/estatística & dados numéricos , Estudantes de Medicina/estatística & dados numéricos , Cirurgiões/estatística & dados numéricos , Feminino , Cirurgia Geral/educação , Cirurgia Geral/legislação & jurisprudência , Cirurgia Geral/organização & administração , Conselho Diretor/legislação & jurisprudência , Conselho Diretor/estatística & dados numéricos , Humanos , Internato e Residência/estatística & dados numéricos , Candidatura a Emprego , Licenciamento em Medicina/legislação & jurisprudência , Masculino , Estudos Retrospectivos , Cirurgiões/economia , Cirurgiões/legislação & jurisprudência , Estados Unidos
19.
Pediatr Surg Int ; 37(10): 1383-1392, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34245339

RESUMO

BACKGROUND: Chronic pancreatitis (CP) and acute recurrent pancreatitis (ARP) in pediatric patients are strongly associated with genetic mutations and lead to pan-parenchymal disease refractory to medical and endoscopic treatment. Our aim was to assess pain resolution and glucose control in patients with CP and ARP following total pancreatectomy with islet auto-transplantation (TPIAT). METHODS: We retrospectively analyzed prospectively collected clinical data of 12 children who developed CP and ARP and underwent TPIAT when 21 years old or younger at the University of Chicago between December 2009 and June 2020. Patients with recurrent or persistent abdominal pain attributed to acute or chronic pancreatic inflammation and a history of medical interventions attempted for the relief of pancreatic pain were selected by a multi-disciplinary team for TPIAT. We followed patients post-operatively and reported data for pre-TPIAT, post-operative day 75, and yearly post-TPIAT. RESULTS: All 12 patients experienced complete resolution of pancreatic pain. The overall insulin-independence rate after 1 year was 66% (8/12) and 50% (3/6) at 4 years. Shorter duration of CP/ARP pre-TPIAT, higher mass of islets infused, and lower BMI, BMI percentile, and BSA were associated with insulin-independence post-TPIAT. CONCLUSIONS: TPIAT is a viable treatment option for pediatric patients with CP and ARP. Pediatric patients undergoing TPIAT for CP achieved resolution of pancreatic-type pain and reduced opioid requirements. The majority were able to achieve insulin-independence which was associated with lower pre-TPIAT BMI and higher islet mass transplanted (i.e., over 2000 IEQ/kg), the latter of which can be achieved by earlier TPIAT. LEVEL OF EVIDENCE: Treatment study, Level IV.


Assuntos
Glicemia , Pancreatite Crônica , Dor Abdominal , Criança , Humanos , Pancreatectomia , Pancreatite Crônica/cirurgia , Estudos Retrospectivos , Transplante Autólogo , Resultado do Tratamento
20.
J Vasc Surg ; 74(2S): 2S-5S, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34303457

RESUMO

Healthcare disparities are a serious problem that shorten the lives of many Americans, even after accounting for social, cultural, and economic factors and correcting for confounders such as the lack of medical insurance and access to healthcare, black Americans and other minority groups receive worse medical care and experience worse outcomes as a result. Healthcare does not occur in a vacuum; surgeons cannot serve our patients' needs isolated in a bubble and cocooned from larger societal concerns. Although disparities rooted in race likely have the greatest negative effects on our patients' health, plenty of groups exist that have not historically received equal opportunities and acceptance within the surgical world. Despite now accounting for more than one half of all medical graduates, women remain underrepresented in leadership positions, and the gender pay gap has remained significant in all branches of medicine. It will require active, multifaceted, and sustained effort to increase diversity, equity, and inclusion in academic surgery. We have described the steps that can be taken within surgical departments and in national surgical societies to recruit, retain, and foster a diverse surgical workforce and to develop a more inclusive culture within surgery and surgical training.


Assuntos
Diversidade Cultural , Equidade de Gênero , Princípios Morais , Seleção de Pessoal , Médicas , Racismo , Sexismo , Cirurgiões , Procedimentos Cirúrgicos Vasculares , Assistência à Saúde Culturalmente Competente/etnologia , Feminino , Disparidades em Assistência à Saúde/etnologia , Direitos Humanos , Humanos , Liderança , Masculino , Mentores , Fatores Raciais , Fatores Sexuais , Sociedades Médicas , Cirurgiões/educação , Procedimentos Cirúrgicos Vasculares/educação
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA