Protein geranylgeranylation (GGylation) is an important biochemical process for many cellular signaling molecules. Previous studies have shown that GGylation is essential for cell survival in many ...types of cancer. However, the molecular mechanism mediating the cell survival effect remains elusive. In this report, we show that the Hippo pathway mediates GGylation-dependent cell proliferation and migration in breast cancer cells. Blockade of GGylation enhanced phosphorylation of Mst1/2 and Lats1, and inhibited YAP and TAZ activity and the Hippo-YAP/TAZ pathway-dependent transcription. The effect of GGylation blockade on inhibition of breast cancer cell proliferation and migration is dependent on the Hippo-YAP/TAZ signaling, in which YAP appears to regulate cell proliferation and TAZ to regulate cell migration. Furthermore, GGylation-dependent cell proliferation is correlated with the activity of YAP/TAZ in breast cancer cells. Finally, Gγ and RhoA are the GGylated proteins that may transduce GGylation signals to the Hippo-YAP/TAZ pathway. Taken together, our studies have demonstrated that the Hippo-YAP/TAZ pathway is essential for GGylation-dependent cancer cell proliferation and migration.
ABSTRACT
Purpose
Survival nomograms offer individualized predictions using a more diverse set of factors than traditional staging measures, including the American Joint Committee on Cancer Tumor Node ...Metastasis (AJCC TNM) Staging System. A nomogram predicting overall survival (OS) for resected, non-metastatic non-small cell lung cancer (NSCLC) has been previously derived from Asian patients. The present study aims to determine the nomogram’s predictive capability in the US using the National Cancer Database (NCDB).
Methods
This was a retrospective review of adults with resected, non-metastatic NSCLC entered into the NCDB between 2004 and 2012. Concordance indices and calibration plots analyzed discrimination and calibration, respectively. Multivariate analysis was also used.
Results
A total of 57,313 patients were included in this study. The predominant histologies were adenocarcinoma (48.2%) and squamous cell carcinoma (31.3%), and patients were diagnosed with stage I-A (38.3%), stage I-B (22.7%), stage II-A (14.2%), stage II-B (11.5%), and stage III-A (13.3%). Median OS was 74 months. 1-, 3- and 5-year OS rates were 89.8% 95% confidence interval (CI) 89.5–90.0%, 71.1% (95% CI 70.7–71.6%), and 55.7% (95% CI 54.7–56.6%), respectively. The nomogram’s concordance index (C-index) was 0.804 (95% CI 0.792–0.817). AJCC TNM staging demonstrated higher discrimination (C-index 0.833, 95% CI 0.821–0.840).
Conclusions
The nomogram’s individualized estimates accurately predicted survival in this patient collective, demonstrating higher discrimination in this population than in the developer’s cohorts. However, the generalized survival estimates provided by traditional staging demonstrated superior predictive capability; therefore, AJCC TNM staging should remain the gold standard for the prognostication of resected NSCLC in the US.
The aim of this study was to evaluate the influence of sex on facultys' perception of resident autonomy and performance.
Autonomy/performance/complexity evaluations performed by faculty of ...categorical general surgery residents (2015-2021) were analyzed. Comparisons of scores by faculty and resident sex were performed.
A total of 10967 paper/electronic evaluations were collected. Female attendings rated female residents significantly lower in autonomy when compared to males (2.75 vs 2.91, p = 0.0037). There was no significant difference in autonomy ratings for male versus female residents when evaluated by a male attending (2.93 vs 2.96, p = 0.054) but male attendings did rate female residents significantly lower in autonomy at the highest complexities (2.37 vs 2.50, p = 0.012).
The data suggests a unique interaction between attending and resident sex. A periodic evaluation of evaluations within one's program may provide invaluable implicit bias insight and should be considered.
The COVID-19 pandemic disrupted the delivery of surgical services. The purpose of this communication was to report the impact of the pandemic on surgical training and learner well-being and to ...document adaptations made by surgery departments.
A 37-item survey was distributed to educational leaders in general surgery and other surgical specialty training programs. It included both closed- and open-ended questions and the self-reported stages of GME during the COVID-19 pandemic, as defined by the ACGME. Statistical associations for items with stage were assessed using categorical analysis.
The response rate was 21% (472 of 2,196). US stage distribution (n = 447) was as follows: stage 1, 22%; stage 2, 48%; and stage 3, 30%. Impact on clinical education significantly increased by stage, with severe reductions in nonemergency operations (73% and 86% vs 98%) and emergency operations (8% and 16% vs 34%). Variable effects were reported on minimal expected case numbers across all stages. Reductions were reported in outpatient experience (83%), in-hospital experience (70%), and outside rotations (57%). Increases in ICU rotations were reported with advancing stage (7% and 13% vs 37%). Severity of impact on didactic education increased with stage (14% and 30% vs 46%). Virtual conferences were adopted by 97% across all stages. Severity of impact on learner well-being increased by stage—physical safety (6% and 9% vs 31%), physical health (0% and 7% vs 17%), and emotional health (11% and 24% vs 42%). Regardless of stage, most but not all made adaptations to support trainees’ well-being.
The pandemic adversely impacted surgical training and the well-being of learners across all surgical specialties proportional to increasing ACGME stage. There is a need to develop education disaster plans to support technical competency and learner well-being. Careful assessment for program advancement will also be necessary. The experience during this pandemic shows that virtual learning and telemedicine will have a considerable impact on the future of surgical education.
Display omitted
Background Learning styles theory posits that learners have distinct preferences for how they assimilate new information. The VARK model categorizes learners based on combinations of 4 learning ...preferences: visual (V), aural (A), read/write (R), and kinesthetic (K). A previous single institution study demonstrated that the VARK preferences of applicants who interview for general surgery residency are different from that of the general population and that learning preferences were associated with performance on standardized tests. This multiinstitutional study was conducted to determine the distribution of VARK preferences among interviewees for general surgery residency and the effect of those preferences on United States Medical Licensing Examination (USMLE) scores. Methods The VARK learning inventory was administered to applicants who interviewed at 3 general surgery programs during the 2014 to 2015 academic year. The distribution of VARK learning preferences among interviewees was compared with that of the general population of VARK respondents. Performance on USMLE Step 1 and Step 2 Clinical Knowledge was analyzed for associations with VARK learning preferences. Chi-square, analysis of variance, and Dunnett’s test were used for statistical analysis, with p < 0.05 considered statistically significant. Results The VARK inventory was completed by a total of 140 residency interviewees. Sixty-four percent of participants were male, and 41% were unimodal, having a preference for a single learning modality. The distribution of VARK preferences of interviewees was different than that of the general population (p = 0.02). By analysis of variance, there were no overall differences in USMLE Step 1 and Step 2 Clinical Knowledge scores by VARK preference (p = 0.06 and 0.21, respectively). However, multiple comparison analysis using Dunnett’s test revealed that interviewees with R preferences had significantly higher scores than those with multimodal preferences on USMLE Step 1 (239 vs. 222, p = 0.02). Conclusion Applicants who interview for general surgery residency have a different pattern of VARK preferences than that of the general population. Interviewees with preferences for read/write learning modalities have higher scores on the USMLE Step 1 than those with multimodal preferences. Learning preferences may have impact on residency applicant selection and represents a topic that warrants further investigation.
Objective Characterize the concordance among faculty and resident perceptions of surgical case complexity, resident technical performance, and autonomy in a diverse sample of general surgery ...procedures using case-specific evaluations. Design A prospective study was conducted in which a faculty surgeon and surgical resident independently completed a postoperative assessment examining case complexity, resident operative performance (Milestone assessment) and autonomy (Zwisch model). Pearson correlation coefficients ( r ) reaching statistical significance (p < 0.05) were further classified as moderate ( r ≥ 0.40), strong ( r ≥ 0.60), or very strong ( r ≥ 0.80). Setting This study was conducted in the General Surgery Residency Program at an academic tertiary care facility (Geisinger Medical Center, Danville, PA). Participants Participants included 6 faculty surgeons, in addition to 5 postgraduate year (PGY) 1, 6 midlevel (PGY 2-3), and 4 chief (PGY 4-5) residents. Results In total, 75 surgical cases were analyzed. Midlevel residents accounted for the highest number of cases (35, 46.6%). Overall, faculty and resident perceptions of case complexity demonstrated a strong correlation ( r = 0.76, p < 0.0001). Technical performance scores were also strongly correlated ( r = 0.66, p < 0.0001), whereas perceptions of autonomy demonstrated a moderate correlation ( r = 0.56, p < 0.0001). Subgroup analysis revealed very strong correlations among faculty perceptions of case complexity and the perceptions of PGY 1 ( r = 0.80, p < 0.0001) and chief residents ( r = 0.82, p < 0.0001). All other intergroup correlations were strong with 2 notable exceptions as follows: midlevel and chief residents failed to correlate with faculty perceptions of autonomy and operative performance, respectively. Conclusions General surgery residents generally demonstrated high correlations with faculty perceptions of case complexity, technical performance, and operative autonomy. This generalized accord supports the use of the Milestone and Zwisch assessments in residency programs. However, discordance among perceptions of midlevel resident autonomy and chief resident operative performance suggests that these trainees may need more direct communication from the faculty.
This study assessed the national impact of the coronavirus disease 2019 (COVID-19) pandemic on the education of medical students assigned to surgery clerkship rotations, as reported by surgery ...clerkship directors (CDs).
In the spring of 2020 and 2021, the authors surveyed 164 CDs from 144 Liaison Committee on Medical Education-accredited US medical schools about their views of the pandemic's impact on the surgery clerkship curriculum, students' experiences, outcomes, and institutional responses.
Overall survey response rates, calculated as number of respondents/number of surveyed, were 44.5% (73 of 164) and 50.6% (83 of 164) for the spring 2020 and 2021 surveys, respectively. Nearly all CDs (more than 95%) pivoted to virtual platforms and solutions. Most returned to some form of in-person learning by winter 2020, and prepandemic status by spring 2021 (46%, 38 of 83). Students' progression to the next year was delayed by 12% (9 of 73), and preparation was negatively impacted by 45% (37 of 83). Despite these data, CDs perceived students' interest in surgical careers was not significantly affected (89% vs 77.0%, p = 0.09). During the 1-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%).
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.
The position of Vice Chair of Education (VCE) is increasingly common in Surgery Departments. The role remains ill-defined. The purpose of this study was to explore perceptions of Department Chairs ...(DCs) and Other Education Stakeholders (OESs) regarding the VCE role.
DCs and OESs at institutions with a VCE were surveyed. Descriptive statistics and cross-tabulations were calculated (SAS V9.4).
The overall response rate was 25% (166/666). There were significant differences in whether DCs and OESs agree that the VCE supports others in fulfilling educational roles (95.2% vs 49.5%, p = 0.0002), is critical in achieving education missions (90.5% vs 56.6%, p = 0.0032), enhances the quality of education (95.3% vs 65.7%, p = 0.0174), and is important to education teams (95.0% vs 68.7%, p = 0.0464).
DCs value the VCE role more so than OESs, whom VCEs support. In order for VCEs to be effective educational leaders in Departments of Surgery, the needs of key stakeholders deserve further clarification.
•The Vice Chair of Education role is increasingly common in Departments of Surgery.•Department Chairs believe the Vice Chair of Education is a highly valuable role.•Other educational stakeholders ascribe significantly less value to this role.•There is confusion as to the roles and responsibilities of a Vice Chair for Education.•The role and value of the Vice Chair of Education should be made more transparent.
PDF
