RESUMEN
Compared with other breast cancer subtypes, triple negative breast cancer (TNBC) is an aggressive malignancy with a high recurrence rate and reduced overall survival. Immune checkpoint inhibition (ICI) has shown modest results in this subgroup, highlighting the need for improved targeted therapeutic options. Notch is a defining feature of TNBC and drives the expression of interleukin-1 beta (IL1ß) and C-C motif chemokine ligand 2 (CCL2). These cytokines are involved in the recruitment of tumor-associated macrophages (TAMs) to the tumor, resulting in immune evasion and tumor progression. Targeting Notch, IL1ß or CCL2 may reduce TAM recruitment and resistance to ICI, illuminating the potential of combination immunotherapy in TNBC.
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Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/terapia , Neoplasias de la Mama Triple Negativas/metabolismo , Quimiocinas , Citocinas , Inmunoterapia , Microambiente TumoralRESUMEN
BACKGROUND: Serious concerns regarding quality of conduct and reporting of noninferiority trials (NITs) have been raised. Systematic analysis of the quality of the surgical NITs is lacking. Assessing the quality of conduct, reporting, and interpretation of surgical NITs in cancer patients is critical given their potential clinical impact. We aim to assess the quality of conduct, reporting, and interpretation of NITs that investigate the effects of surgical management in cancer patients. METHODS: A cross-sectional analysis of papers identified through a comprehensive literature database search was performed. Forty papers employing a phase III noninferiority (NI) randomized trial design to study effects of surgical methodology or sequencing of surgery in patients with solid cancers were included. Papers were assessed for type of analysis, justification of the noninferiority margin (NIM), consistency of type I error with confidence intervals (CIs), ability to achieve the predefined sample size, and interpretations regarding NI. RESULTS: Only half of the papers used both intention-to-treat and per protocol analyses; 62.5% provided no or poor justification for the NIM; 42.5% showed inconsistency of the type I error rate with CIs; 52.5% were deemed poor or fair quality, and 60.0% did not achieve the predefined sample size. One-fifth of the papers provided interpretation of the NI hypothesis that was not in concordance with the CONSORT guidelines. CONCLUSIONS: The quality of conduct, reporting, and interpretation of surgical NITs is suboptimal, requiring further improvements through adherence to guidelines and rigorous assessment at the stages of the study approval, funding, and the peer-review process.
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Neoplasias , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Transversales , Estudios de Equivalencia como Asunto , Humanos , Neoplasias/cirugíaRESUMEN
Importance: Within medical specialties, surgical disciplines disproportionately and routinely demonstrate the greatest underrepresentation of women and individuals from racial/ethnic minority groups. Understanding the role that diversity plays in surgical resident training may identify strategies that foster resident resiliency, optimize surgical training, and improve patient outcomes. Objective: To examine the implication of gender and visible minority (VM [ie, nonaboriginal people who are not White individuals]) status for resiliency and training experiences of general surgery residents in Canada. Design, Setting, and Participants: In this survey study, a 129-item questionnaire was emailed from May 2018 to July 2018 to all residents enrolled in all Canadian general surgery training programs during the 2017-2018 training year. Survey responses were extracted and categorized into 5 major themes. The survey was designed by the Resident Committee and reviewed by the Governing Board of the Canadian Association of General Surgeons. French and English versions of the survey were created, distributed, and administered using Google Forms. Main Outcomes and Measures: Survey questions were formulated to characterize resident diversity and training experience. Self-perceptions of diversity, mentorship, and training experience were evaluated using a 5-point Likert scale (1 for strongly disagree, 2 for disagree, 3 for neither agree or disagree, 4 for agree, and 5 for strongly agree) and open-ended responses. The frequency of perceived unprofessional workplace encounters was evaluated using a 5-point scale (1 for daily, 2 for weekly, 3 for monthly, 4 for annually, and 5 for never). Results: Of the 510 general surgery residents invited, a total of 210 residents (40.5%) completed the survey. Most respondents were younger than 30 years (119 [56.7%]), were women (112 [53.3%]), reported English as their first language (133 [63.3%]), did not identify as a VM (147 [70.0%]), had no dependents (184 [87.6%]), and were Canadian medical graduates (178 [84.8%]). Women residents who identified as VM compared with male residents who did not identify as a VM were less likely to agree or strongly agree that they had a collegial relationship with staff, (21 [63.6%] vs 61 [89.7%]; P = .01), to feel like they fit in with their training programs (21 [63.6%] vs 56 [82.3%]; P = .003), and to feel valued at work (15 [45.4%] vs 47 [69.1%]; P = .03). Both female residents and female residents who identified as VM described significant concerns about receiving fewer training opportunities because of their gender vs their male peers (54 [48.2%] vs 3 [3.0%]; P < .001). Ninety-one of 112 female residents (81.2%) reported feeling that their medical expertise was dismissed because of their gender at least once annually, with 37 women (33.0%) experiencing dismissal of their expertise at least once every week (P < .001). In contrast, 98% of male residents reported never experiencing dismissal of their medical expertise because of their gender. Similarly, residents with VM status vs those without VM status reported at least monthly dismissal of their expertise because of their race/ethnicity (9 of 63 [14.3%] vs 1 of 147 [0.7%]; P < .001). Conclusions and Relevance: In this study, female sex and VM status appeared to be associated with adverse implications for the training experience of general surgery residents. These findings suggest that new strategies focused on the intersectionality of gender and race/ethnicity are needed to improve the training experience of at-risk residents.
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Actitud del Personal de Salud/etnología , Educación/estadística & datos numéricos , Etnicidad/psicología , Cirugía General/educación , Cirugía General/estadística & datos numéricos , Internado y Residencia/estadística & datos numéricos , Grupos Minoritarios/psicología , Racismo/psicología , Adulto , Canadá/epidemiología , Diversidad Cultural , Etnicidad/estadística & datos numéricos , Femenino , Estado de Salud , Encuestas Epidemiológicas , Humanos , Masculino , Grupos Minoritarios/estadística & datos numéricos , Racismo/estadística & datos numéricos , Resiliencia Psicológica , Factores Sexuales , Encuestas y CuestionariosRESUMEN
BACKGROUND: Several models have been introduced to improve and restructure surgical training, but continued barriers exist. Residents are uniquely positioned to offer perspective on practical challenges and needs of reformatting surgical education. This study aimed to establish a nationwide, Delphi consensus statement on the perceptions of Canadian residents regarding the future of general surgery training. METHODS: Canadian general surgery residents participated in a moderated focus group using the Nominal Group Technique to discuss early subspecialization, competency-based medical education, and transition to practice. Qualitative verbal data were transcribed, categorized into themes, and synthesized into recommendation statements. During an iterative Delphi survey, resident leaders ranked each statement on a 5-point Likert scale of agreement. The survey was terminated once consensus was achieved (≥2 survey rounds and Cronbach's α ≥ 0.80). RESULTS: A total of 66 statements were synthesized by 16 members of the Canadian Association of General Surgeons Resident Committee. A total of 49 residents participated in the Delphi consensus, which was achieved after 2 voting rounds (Cronbach's α = 0.93). Participants agreed that (1) residency should focus on achieving standardized competencies and milestones based on resident ability to meet specific measurable metrics, (2) early streaming should be offered after "core" milestones and competencies have been achieved, and (3) an explicit period should allow transition-to-independent practice with tailored rotations, greater autonomy, and resident-run clinics. We identified 10 barriers to competency-based medical education implementation. CONCLUSION: A nationwide consensus regarding the future of surgical training was established among current residents. These findings can inform and help implement guidelines and national curricula that meet the needs of the trainee and address the many challenges they face during their training.
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Educación Basada en Competencias/tendencias , Consenso , Cirugía General/educación , Internado y Residencia/tendencias , Modelos Educacionales , Adulto , Canadá , Competencia Clínica , Educación Basada en Competencias/métodos , Técnica Delphi , Femenino , Grupos Focales , Humanos , Internado y Residencia/métodos , Masculino , Investigación Cualitativa , Cirujanos/educaciónRESUMEN
BACKGROUND: Guidelines recommend biologic prosthetics for ventral hernia repair (VHR) in contaminated fields, yet long-term and patient-reported data are limited. We aimed to determine the long-term rate of hernia recurrence, and other clinical and patient-reported outcomes following the use of porcine small intestine submucosa (PSIS) for VHR in a contaminated field. METHODS: Consecutive patients undergoing open VHR with PSIS mesh in a contaminated field from 2004 to 2014 were prospectively evaluated for hernia recurrence and other post-operative complications. Multivariate logistic and Cox regression analyses identified predictors of hernia recurrence and surgical site infection. Patient-reported outcomes were evaluated using SF-36, Hernia-Related Quality-of-Life Survey (HerQLes) and Body Image Questionnaire instruments. RESULTS: Forty-six hernias were repaired in clean-contaminated [16 (35 %)], contaminated [11 (24 %)] and dirty [19 (41 %)] fields. Median follow-up was 47 months [interquartile range: 31-79] and all patients had greater than 12-month follow-up. Sixteen patients (35 %) were not re-examined. Incidence of surgical site events and surgical site infection were 43 % (n = 20) and 56 % (n = 25), respectively. American Society of Anesthesiologists score 3 or greater was an independent predictor of surgical site infection (odds ratio 5.34 [95 % confidence interval 1.01-41.80], p = 0.04). Hernia recurrence occurred in 61 % (n = 28) with a median time to diagnosis of 16 months [interquartile range 8-26]. After bridged repair, 16 of 18 patients (89 %) recurred, compared to 12 of 28 (43 %) when fascia was approximated (p < 0.01). Bridged repair was an independent predictor of recurrence (odds ratio 10.67 [95 % confidence interval 2.42-76.08], p < 0.01). Patients with recurrences had significantly worse scores on the SF-36 mental health component and self-perceived body image, whereas HerQLes scores were similar. CONCLUSIONS: Hernia recurrences and wound infections are high with the use of biologic PSIS mesh in contaminated surgical fields. Careful consideration is warranted using this approach.