Quantifying Impact of Disruption to Radiology Education During the COVID-19 Pandemic and Implications for Future Training.

PURPOSE: The aim of this study was to assess the impact on radiology resident education due to the COVID-19 pandemic in order to inform future educational planning. METHODS: During a 10-week study period from March 16 to May 22, 2020, changes to educational block-weeks (BW) of first through fourth year residents (R1-4) were documented as disrupted in the setting of the COVID-19 pandemic. The first 5 weeks and the second 5 weeks were evaluated separately for temporal differences. Overall and mean disrupted BW per resident were documented. Wilcoxon rank-sum tests were used to assess pairwise differences between classes with Bonferroni-adjusted P-values, as well as differences in the early versus later phase of the pandemic. RESULTS: Of 373 BW, 56.6% were assigned to virtual curriculum, 39.4% radiology clinical duties, 2.9% illness, and 1.1% reassignment. Scheduling intervention affected 6.2 ± 2.3 (range 1-10) mean BW per resident over the 10-week study period. The R3 class experienced the largest disruption, greater than the R2 classes, and statistically significantly more than the R1 and R4 classes (both P < 0.05). The second half of the pandemic caused statistically significantly more schedule disruptions than the first half (P = 0.009). DISCUSSION: The impact of COVID-19 pandemic varied by residency class year, with the largest disruption of the R3 class and the least disruption of the R4 class. To optimize future educational opportunities, shifting to a competency-based education paradigm may help to achieve proficiency without extending the length of the training program.

Intraprocedural MRI monitoring during percutaneous cryoablation procedures of the head and neck, and spine: a single institution experience.

RATIONALE AND OBJECTIVES: Evaluate whether intraprocedural MRI monitoring of percutaneous cryoablation procedures of head and neck, and spine lesions is effective for avoiding iatrogenic neurovascular and mucosal injury. MATERIALS AND METHODS: We retrospectively reviewed 64 consecutive percutaneous head and neck, and spine cryoablation procedures with intraprocedural MRI monitoring performed on 45 patients (mean age 55 years, range 17-91 years). Ablation goals were either complete local control of primary or metastatic lesions or pain relief. RESULTS: The technical success rate was 100%. The complication rate was 13% with only 2 complications (3%) requiring further intervention. There were no deaths or persistent neurological or vascular complications. Subsequent cryoablation in the same location was performed in 12 patients (27%). Subsequent surgical intervention in the same location was performed in 7 patients (16%) for progressive disease or worsening symptoms. CONCLUSIONS: MRI provides excellent visualization of the ice ball margin during percutaneous cryoablation procedures. Accurate intraprocedural visualization of the ice ball allows for adjustment of cryoablation parameters to avoid damage to adjacent vital neurovascular structures or mucosal surfaces. Intraprocedural MRI monitoring is thus a novel and highly effective method that allows a high rate of technical success for cryoablation in the head and neck, and spine while avoiding iatrogenic injury.

Beyond business as usual: Radiology residency educational response to the COVID-2019 pandemic.

The COVID-19 pandemic has disrupted standard hospital operations and diagnostic radiology resident education at academic medical centers across the country. Deferment of elective surgeries and procedures coupled with a shift of resources toward increased inpatient clinical needs for the care of COVID-19 patients has resulted in substantially decreased imaging examinations at many institutions. Additionally, both infection control and risk mitigation measures have resulted in minimal on-site staffing of both trainees and staff radiologists at many institutions. As a result, residents have been placed in nonstandard learning environments, including working from home, engaging in a virtual curriculum, and participating in training sessions in preparation for potential reassignment to other patient care settings. Typically, for residents to gain the necessary knowledge, skills, and experience to practice independently upon graduation, radiology training programs must provide an optimal balance between resident education and clinical obligations. We describe our experience adapting to the challenges in educational interruptions and clinical work reassignments of 41 interventional and diagnostic radiology residents at a large academic center. We highlight opportunities for collaboration and teamwork in creatively adjusting and planning for the short and long-term impact of the pandemic on resident education. This experience shows how the residency educational paradigm was shifted during a pandemic and can serve as a template to address future disruptions.

The Role of Extent of Resection in IDH1 Wild-Type or Mutant Low-Grade Gliomas.

BACKGROUND: Maximizing extent of resection (EOR) improves outcomes in adults with World Health Organization (WHO) grade II low-grade gliomas (LGG). However, recent studies demonstrate that LGGs bearing a mutation in the isocitrate dehydrogenase 1 (IDH1) gene are a distinct molecular and clinical entity. It remains unclear whether maximizing EOR confers an equivalent clinical benefit in IDH mutated (mtIDH) and IDH wild-type (wtIDH) LGGs. OBJECTIVE: To assess the impact of EOR on malignant progression-free survival (MPFS) and overall survival (OS) in mtIDH and wtIDH LGGs. METHODS: We performed a retrospective review of 74 patients with WHO grade II gliomas and known IDH mutational status undergoing resection at a single institution. EOR was assessed with quantitative 3-dimensional volumetric analysis. The effect of predictor variables on MPFS and OS was analyzed with Cox regression models and the Kaplan-Meier method. RESULTS: Fifty-two (70%) mtIDH patients and 22 (30%) wtIDH patients were included. Median preoperative tumor volume was 37.4 cm3; median EOR of 57.6% was achieved. Univariate Cox regression analysis confirmed EOR as a prognostic factor for the entire cohort. However, stratifying by IDH status demonstrates that greater EOR independently prolonged MPFS and OS for wtIDH patients (hazard ratio [HR] = 0.002 [95% confidence interval {CI} 0.000-0.074] and HR = 0.001 [95% CI 0.00-0.108], respectively), but not for mtIDH patients (HR = 0.84 [95% CI 0.17-4.13] and HR = 2.99 [95% CI 0.15-61.66], respectively). CONCLUSION: Increasing EOR confers oncologic and survival benefits in IDH1 wtLGGs, but the impact on IDH1 mtLGGs requires further study.

Sex, Age, Anatomic Location, and Extent of Resection Influence Outcomes in Children With High-grade Glioma.

BACKGROUND: Survival duration and prognostic factors in adult high-grade glioma have been comprehensively analyzed, but less is known about factors contributing to overall survival (OS) and progression-free survival (PFS) in pediatric patients. OBJECTIVE: To identify these factors in the pediatric population. METHODS: We retrospectively reviewed institutional databases evaluating all patients ≤21 years with high-grade glioma treated between 1988 and 2010. Kaplan-Meier curves and log-rank statistics were used to compare groups univariately. Multivariate analyses were completed using Cox proportional hazards regression models. RESULTS: Ninety-seven patients were identified with a median age of 11 years. Median OS was 1.7 years, and median PFS was 272 days. Location was significant for OS (P < .001). Patients with gross total resection (GTR) had a median OS of 3.4 years vs 1.6 years for subtotal resection and 1.3 years for biopsy patients (P < .001). Female patients had improved OS (P = .01). Female patients with GTR had a mean OS of 8.1 years vs 2.4 years for male patients with GTR and 1.4 years for all other female patients and male patients (P = .001). PFS favored patients ≤3 and ≥13 years and females (P = .003 and .001). CONCLUSION: OS was significantly correlated with the location of the tumor and the extent of resection. GTR significantly improved overall survival for both glioblastoma multiforme and anaplastic astrocytoma patients, and female patients showed a much larger survival benefit from GTR than male patients.

Subtype-specific MEK-PI3 kinase feedback as a therapeutic target in pancreatic adenocarcinoma.

Mutations in the KRAS oncogene are dominant features in pancreatic ductal adenocarcinoma (PDA). Because KRAS itself is considered "undruggable," targeting pathways downstream of KRAS are being explored as a rational therapeutic strategy. We investigated the consequences of MAP-ERK kinase (MEK) inhibition in a large PDA cell line panel. Inhibition of MEK activated phosphoinositide 3-kinase in an EGF receptor (EGFR)-dependent fashion and combinations of MEK and EGFR inhibitors synergistically induced apoptosis. This combinatorial effect was observed in the epithelial but not mesenchymal subtype of PDA. RNA expression analysis revealed predictors of susceptibility to the combination, including E-cadherin, HER3, and the miR200-family of microRNAs, whereas expression of the transcription factor ZEB1 was associated with resistance to the drug combination. Knockdown of HER3 in epithelial-type and ZEB1 in mesenchymal-type PDA cell lines resulted in sensitization to the combination of MEK and EGFR inhibitors. Thus, our findings suggest a new, subtype-specific, and personalized therapeutic strategy for pancreatic cancer.

Effects of CETP inhibition on triglyceride-rich lipoprotein composition and apoB-48 metabolism.

Cholesteryl ester transfer protein (CETP) facilitates the transfer of HDL cholesteryl ester to triglyceride-rich lipoproteins (TRL). This study aimed to determine the effects of CETP inhibition with torcetrapib on TRL composition and apoB-48 metabolism. Study subjects with low HDL cholesterol (<40 mg/dl), either untreated (n = 9) or receiving atorvastatin 20 mg daily (n = 9), received placebo for 4 weeks, followed by torcetrapib 120 mg once daily for the next 4 weeks. A subset of the subjects not treated with atorvastatin participated in a third phase (n = 6), in which they received torcetrapib 120 mg twice daily for an additional 4 weeks. At the end of each phase, all subjects received a primed-constant infusion of [5,5,5-(2)H(3)]L-leucine, while in the constantly fed state, to determine the kinetics of TRL apoB-48 and TRL composition. Relative to placebo, torcetrapib markedly reduced TRL CE levels in all groups (≥-69%; P < 0.005). ApoB-48 pool size (PS) and production rate (PR) decreased in the nonatorvastatin once daily (PS: -49%, P = 0.007; PR: -49%, P = 0.005) and twice daily (PS: -30%, P = 0.01; PR: -27%, P = 0.13) cohorts. In the atorvastatin cohort, apoB-48 PS and PR, which were already lowered by atorvastatin, did not change with torcetrapib. Our findings indicate that CETP inhibition reduced plasma apoB-48 concentrations by reducing apoB-48 production but did not have this effect in subjects already treated with atorvastatin.

Impact of mifepristone, a glucocorticoid/progesterone antagonist, on HDL cholesterol, HDL particle concentration, and HDL function.

CONTEXT: Mifepristone is a glucocorticoid and progestin antagonist under investigation for the treatment of Cushing's syndrome. Mifepristone decreases high-density lipoprotein (HDL) cholesterol (HDL-C) levels in treated patients, but the clinical significance of this is unclear because recent studies suggest that functional properties of HDL predict cardiovascular disease status better than does HDL-C concentration. OBJECTIVE: The aim of the study was to characterize the impact of mifepristone administration on HDL particle concentration and function. DESIGN AND SETTING: We conducted a double-blind, randomized, placebo-controlled trial at a single-site, clinical research center. PARTICIPANTS: Thirty healthy postmenopausal female volunteers participated in the study. INTERVENTION: Individuals were randomized to receive daily oral mifepristone (600 mg) or placebo for 6 wk. MAIN OUTCOME MEASURES: We measured HDL-C, serum HDL particle concentration, and HDL-mediated cholesterol efflux by treatment group. RESULTS: As expected, ACTH, cortisol, estradiol, and testosterone levels increased in the mifepristone group. Mifepristone treatment decreased HDL-C and HDL particle concentration by 26 and 25%, respectively, but did not alter pre-ß HDL concentration. In contrast, the serum HDL-mediated cholesterol efflux decreased with mifepristone treatment by only 12%, resulting in an effective increase of the efflux capacity per HDL particle. No changes were observed in cholesterol ester transfer protein or lecithin:cholesterol acyltransferase activity. CONCLUSIONS: Treatment with mifepristone reduced HDL-C, HDL particle concentration, and serum HDL cholesterol efflux in postmenopausal women. However, on a per particle basis, the efflux capacity of serum HDL increased. These observations support the concept that a decrease in HDL-C may not represent proportional impairment of HDL function.

Effects of the cholesteryl ester transfer protein inhibitor torcetrapib on VLDL apolipoprotein E metabolism.

Cholesteryl ester transfer protein (CETP) inhibition leads to changes in lipoprotein metabolism. We studied the effect of the CETP inhibitor torcetrapib on VLDL apolipoprotein E (apoE) metabolism. Subjects, pretreated with atorvastatin (n = 9) or untreated (n = 10), received placebo followed by torcetrapib (4 weeks each). After each treatment, subjects underwent a primed-constant infusion of D(3)-leucine to determine the VLDL apoE production rate (PR) and fractional catabolic rate (FCR). Torcetrapib alone reduced the VLDL apoE pool size (PS) (-28%) by increasing the VLDL apoE FCR (77%) and leaving the VLDL apoE PR unchanged. In subjects pretreated with atorvastatin, torcetrapib increased the VLDL apoE FCR (25%) and PR (21%). This left the VLDL apoE PS unchanged but increased the VLDL apoE content, likely enhancing VLDL clearance and reducing LDL production in this group. Used alone, torcetrapib reduces the VLDL apoE PS by increasing the apoE FCR while leaving the VLDL apoE content unchanged. In contrast, torcetrapib added to atorvastatin treatment increases both the VLDL apoE FCR and PR, leaving the VLDL apoE PS unchanged. Adding torcetrapib to atorvastatin treatment increases the VLDL apoE content, likely leading to decreased conversion of VLDL to LDL, reduced LDL production, and lower levels of circulating VLDL and LDL.