A Burnout Reduction and Wellness Strategy: Personal Financial Health for the Medical Trainee and Early Career Radiation Oncologist

PurposePhysician burnout is reported in more than one out of every 2 practicing clinicians and is just as prevalent in training physicians. Burnout severity is also associated with increasing levels of financial debt. Medical professionals are notable for their high and increasing levels of debt; despite this, financial literacy is poor among physicians, and financial education is largely absent from medical education. Radiation oncologists (ROs) are no different in this regard, with 33% of residents reporting high levels of burnout symptoms, 33% carrying >$200,000 of educational debt, and 75% reporting being unprepared to handle future financial decisions. To fill this gap, we reviewed the basic tenets of personal financial health for the early career RO.Methods and materialsThe core concept of financial independence (FI) is introduced, and we review 4 basic tenets of personal financial health for the young medical professional: debt, behavior, investment, and asset protection strategies.ResultsFI is achieved by saving until the desired quality of life can be maintained, independent of employment income. Debt strategy involves minimizing debt accrual, understanding student loans, and having a debt management plan. Behavioral strategy involves setting financial goals, calculating worth and a savings rate, budgeting, and frugal living. The basics of investing include asset allocation, diversification, rebalancing, and minimizing expenses. Finally, asset protection includes insuring against catastrophic events with disability, life, health, liability, and property insurance.ConclusionsHealthy financial practices can lead to FI and may facilitate professional and personal freedoms with the goal of mitigating burnout-associated stressors. The tenets of strong financial health for ROs in the early stages of their career include sound debt, behavioral, investment, and asset protection strategies. Furthermore, initial and continuing financial education is an overlooked but important curriculum component. ROs with their financial houses in order can devote more resources to learning and practicing good medicine while living healthy, rewarding lives.     

Preclinical Modeling of Osimertinib for NSCLC With EGFR Exon 20 Insertion Mutations

IntroductionNSCLC with EGFR exon 20 insertion mutations is the third most common type of EGFR-mutant NSCLC and is resistant to EGFR tyrosine kinase inhibitors (TKIs). This study was conducted to evaluate the efficacies of first- to third-generation EGFR TKIs against NSCLC cells harboring EGFR exon 20 insertion mutations.MethodsWe developed seven EGFR exon 20 insertion-mutant Ba/F3 models and one patient-derived NSCLC (SNU-3173) of subtypes A763insFQEA, V769insASV, D770insSVD, D770insNPG, P772insPR, H773insH, H773insNPH, and H773insAH. Cell viability assays, immunoblotting, and N-ethyl-N-nitrosourea mutagenesis screenings were performed. EGFR exon 20 insertion–mutant structures and couplings with osimertinib, a third-generation EGFR TKI, were modeled and compared.ResultsEGFR exon 20 insertion–mutant NSCLC cells, excluding EGFR A763insFQEA, were resistant to first-generation EGFR TKIs (concentration that inhibits 50% [IC₅₀], 1.1 ± 0.067 to 5.4 ± 0.115 μM). Mutants were sensitive to second-generation EGFR TKIs (IC₅₀, 0.02 ± 0.0002 to 161.8 ± 18.7nM), except EGFR H773insH (IC₅₀, 46.3 ± 8.0 to 352.5 ± 22.7nM). The IC₅₀ ratios for mutant to wild-type cells were higher than those for third-generation EGFR TKIs. Third-generation EGFR TKI osimertinib was highly potent against EGFR exon 20 insertion–mutant cells (IC₅₀, 14.7-62.7 nM), including EGFR H773insH, and spared wild-type EGFR cells. N-ethyl-N-nitrosourea mutagenesis screening of EGFR exon 20 insertion–mutant Ba/F3 cells showed various second sites for EGFR mutations, mostly at exons 20 and 21, including E762K, P794S, and G796D. In addition, osimertinib-resistant cells were established by stepwise exposure to osimertinib and harbored EGFR E762K mutation.ConclusionsOsimertinib is active against EGFR exon 20 insertion–mutant NSCLC and flexibly binds within drug-binding pockets in preclinical models.     

The Effect of Psychiatric Diagnosis and Psychotropic Medication on Outcomes Following Total Hip and Total Knee Arthroplasty

BackgroundNearly 20% of the US adult population lives with mental illness, and less than 50% of these receive treatment. Preoperative mental health may affect postoperative outcomes in patients undergoing total joint arthroplasty (TJA), yet is rarely addressed; poor outcomes increase the cost of care and burden on the healthcare system. This study examines the influence of patients with psychiatric diagnosis (PD) and taking psychotropic medication (PM) on emergency room visits, readmissions, and discharge disposition following TJA.MethodsSingle institution retrospective analysis of a consecutive series of 3020 primary TJA performed between January 2017 and June 2018. Chi-squared, t-tests, and analysis of variance were used to quantify differences between groups.ResultsNine hundred seventy-six (32.3%) patients had a PD, most had depression (10.1%), anxiety (8.6%), or both (8.4%); 808 (26.8%) patients were on PM. Patients with PD were more likely to experience emergency room visits (6.3% vs 10.0%, P = .034) and skilled nursing facility discharge (11.6% vs 17.9%, P = .005). Patients taking PM were more likely to experience skilled nursing facility discharge (12.4 vs 17.1, P = .047); those taking >2 PM had the highest rate (21.6%).ConclusionPatients with PD on or off PM may experience increased healthcare utilization in the postoperative period. Increased patient education and support may reduce these discrepancies. PD is not a deterrent for TJA, but targeted interventions should be developed to provide additional support where needed and avoid unnecessary utilization of resources.     

miR-101 Represses T-Cell Acute Lymphoblastic Leukemia by Targeting CXCR7/STAT3 Axis

Although miR-101 is involved in the development and progression of T-cell acute lymphoblastic leukemia (T-ALL), the underlying molecular mechanisms remain unclear. In this article, we report that miR-101 expression was inversely correlated with CX chemokine receptor 7 (CXCR7) level in T-ALL. Introducing miR-101 inhibited T-ALL cell proliferation and invasion in vitro and suppressed tumor growth and lung metastasis in vivo. CXCR7 was identified as a direct target of miR-101. The inhibitory effects of miR-101 were mimicked and counteracted by CXCR7 depletion and overexpression, respectively. Mechanistically, miR-101 targets CXCR7/STAT3 axis to reduce T-ALL growth and metastasis. Overall, these findings implied the potential application of miR-101 and CXCR7 in T-ALL treatment.     

Altered function of the glutamate–aspartate transporter GLAST,a potential therapeutic target in glioblastoma

In glioma patients, high levels of glutamate can cause brain edema and seizures. GLAST, a glutamate–aspartate transporter expressed by astrocytes with a role in glutamate uptake, is highly expressed on the plasma membrane of glioblastoma (GBM) cells, and its expression significantly correlates with shortened patient survival. Here, it was demonstrated that inhibition of GLAST expression limited the progression and invasion of GBM xenografts. Magnetic resonance spectroscopy was used to measure glutamate in GLAST-expressing gliomas showing that these tumors exhibit increased glutamate concentration compared to GLAST-depleted glioma. Despite their GLAST expression, GBM stem-like cells (GSCs) released rather than taking up glutamate due to their lack of Na+/K+-ATPase. Overexpression of Na+/K+-ATPase in these cells restored glutamate uptake and induced apoptosis. The therapeutic relevance of targeting GLAST in gliomas was assessed using the inhibitor UCPH-101. In glioma-bearing mice, a single intratumoral injection of UCPH-101 significantly increased survival by decreasing GLAST expression and inducing apoptosis. Thus, GLAST has a novel role in GBM that appears to have crucial relevance in glutamate trafficking and may thus be a new therapeutic target.