National Comparison of Program Director Perceptions vs. Resident Reports of the Learning Environment and Well-Being.

OBJECTIVE: Our research objectives were to (1) assess the correlation between PD perceptions and their residents' reported experiences and (2) identify PD and program characteristics associated with alignment between PD perceptions and their residents' reports. DESIGN, SETTING, PARTICIPANTS: A survey was administered to US general surgery residents following the 2019 American Board of Surgery In-Training Examination (ABSITE) to study wellness (burnout, thoughts of attrition, and suicidality) and mistreatment (gender discrimination, sexual harassment, racial/ethnic/religious discrimination, bullying). General surgery program directors (PDs) were surveyed about the degree to which they perceived mistreatment and wellness within their programs. Concordance between PDs' perceptions and their residents' reports was assessed using Spearman correlations. Multivariable logistic regression models examined factors associated with alignment between PDs and residents. RESULTS: Of 6,126 residents training at SECOND Trial-enrolled programs, 5,240 (85.5%) responded to the ABSITE survey. All 212 PDs of programs enrolled in the SECOND Trial (100%) responded to the PD survey. Nationally, the proportion of PDs perceiving wellness issues was similar to the proportion of residents reporting them (e.g., 54.9% of PDs perceive that burnout is a problem vs. 40.1% of residents experience at least one burnout symptom weekly); however, the proportion of PDs perceiving mistreatment vastly underestimated the proportion of residents reporting it (e.g., 9.3% of all PDs perceive vs. 65.9% of all residents report bullying). Correlations between PDs' perceptions of problems within their program and their residents' reports were weak for racial/ethnic/religious discrimination (r = 0.176, p = 0.019), sexual harassment (r = 0.180, p = 0.019), burnout (r = 0.198, p = 0.007), and thoughts of attrition (r = 0.193, p = 0.007), and non-existent for gender discrimination, bullying, or suicidality. Multivariable regression models did not identify any program or PD characteristics that were consistently associated with improved resident-program director alignment. CONCLUSIONS: Resident and PD perceptions were generally disparate regarding mistreatment, burnout, thoughts of attrition, and suicidality. Reconciling this discrepancy is critical to enacting meaningful change to improve the learning environment and resident well-being.

Sex-Based Disparities in Timeliness of Trauma Care and Discharge Disposition.

Importance: Differences in time to diagnostic and therapeutic measures can contribute to disparities in outcomes. However, whether there is an association of timeliness by sex for trauma patients is unknown. Objective: To investigate whether sex-based differences in time to definitive interventions exist for trauma patients in the US and whether these differences are associated with outcomes. Design, Setting, and Participants: This was a retrospective cohort study conducted from July 2020 to July 2021, using the 2013 to 2016 Trauma Quality Improvement Program (TQIP) databases from level I to III trauma centers in the US. Patients 18 years or older with an Injury Severity Score (ISS) greater than 15 and who carried diagnoses of traumatic brain injury, intra-abdominal injury, pelvic fracture, femur fracture, and spinal injury as a result of their trauma were included in the study. Data were analyzed from July 2020 to July 2021. Main Outcomes and Measures: Primary outcomes assessed timeliness to interventions, using Wilcoxon signed rank and χ2 tests. Secondary outcomes included location of discharge after injury, using propensity score-matched generalized estimating equations modeling. Results: Of the 28 332 patients included, 20 002 (70.6%) were male patients (mean [SD] age, 43.3 [18.2] years) and 8330 (29.4%) were female patients (mean [SD] age, 48.5 [21.1] years), with significantly different distributions of ISS scores (ISS score 16-24: male patient, 10 622 [53.1%]; female patient, 4684 [56.2%]; ISS score 41-74: male patient, 2052 [10.3%]; female patient, 852 [10.2%]). Male patients more frequently had abdominal (4257 [21.3%] vs 1268 [15.2%]) and spinal cord (3989 [20.0%] vs 1274 [15.3%]) injuries, whereas female patients experienced greater proportions of femur (3670 [44.0%] vs 8422 [42.1%]) and pelvic (3970 [47.6%] vs 6963 [34.8%]) fractures. Female patients experienced significantly longer emergency department length of stay (median [IQR], 184 [92-314] minutes vs 172 [86-289] minutes; P < .001), longer time in pretriage (median [IQR], 52 [36-80] minutes vs 49 [34-77] minutes; P < .001), and increased likelihood of discharge to nursing or long-term care facilities instead of home after matching by age, ISS, mechanism, and injury type (male patient:female patient, odds ratio, 0.72; 95% CI, 0.67-0.78). Conclusions and Relevance: Results of this cohort study suggest that female trauma patients experienced slightly longer delays in trauma care and had a higher likelihood of discharge to long-term care facilities than their male counterparts.

Serum exosomes and cytokines promote a T-helper cell type 2 environment in the peripheral blood of glioblastoma patients.

BACKGROUND: Glioblastoma (GBM) is an aggressive infiltrative brain tumor with a particularly poor prognosis that is characterized by microvascular proliferation, necrotic tissue, and significant infiltration of M2-like monocytes. Compromised barrier function in tumor vasculature might be expected to permit communication between the tumor microenvironment and peripheral blood. METHODS: To ascertain whether tumor-derived vesicles and/or factors might reach the bloodstream and what effects these molecules have on the peripheral compartment, we analyzed blood samples collected from primary GBM patients. RESULTS: Notably, a significant number of patient sera samples contained tumor exosome-reactive immunoglobulin (Ig)G2 and IgG4 antibody isotypes, which are consistent with Th2 immunity. M2-like monocytes expressing CD14+ and CD163+, another indicator of Th2 bias, are elevated in GBM patient blood and associated with high serum concentrations of colony-stimulating factor 2 and 3, as well as interleukin-2, -4, and -13, the latter 2 cytokines being hallmarks of Th2 immunity. GBM patient sera samples induce high levels of CD163 expression when added to normal monocytes, providing mechanistic evidence of a basis for Th2 bias. Fractionation of GBM patient sera into samples enriched for exosomes or soluble factors proved that both fractions are capable of inducing CD163 expression in normal monocytes. CONCLUSIONS: The results of the current study indicate a Th2 bias in the periphery of GBM patients, likely as a result of products elaborated by the tumor. Consequentially, through immune modulation these brain tumors exert systemic effects beyond the confines of the CNS.

Glioblastoma exosomes and IGF-1R/AS-ODN are immunogenic stimuli in a translational research immunotherapy paradigm.

Glioblastomas are primary intracranial tumors for which there is no cure. Patients receiving standard of care, chemotherapy and irradiation, survive approximately 15 months prompting studies of alternative therapies including vaccination. In a pilot study, a vaccine consisting of Lucite diffusion chambers containing irradiated autologous tumor cells pre-treated with an antisense oligodeoxynucleotide (AS-ODN) directed against the insulin-like growth factor type 1 receptor was found to elicit positive clinical responses in 8/12 patients when implanted in the rectus sheath for 24 h. Our preliminary observations supported an immune response, and we have since reopened a second Phase 1 trial to assess this possibility among other exploratory objectives. The current study makes use of a murine glioma model and samples from glioblastoma patients in this second Phase 1 trial to investigate this novel therapeutic intervention more thoroughly. Implantation of the chamber-based vaccine protected mice from tumor challenge, and we posit this occurred through the release of immunostimulatory AS-ODN and antigen-bearing exosomes. Exosomes secreted by glioblastoma cultures are immunogenic, eliciting and binding antibodies present in the sera of immunized mice. Similarly, exosomes released by human glioblastoma cells bear antigens recognized by the sera of 6/12 patients with recurrent glioblastomas. These results suggest that the release of AS-ODN together with selective release of exosomes from glioblastoma cells implanted in chambers may drive the therapeutic effect seen in the pilot vaccine trial.