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.

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.

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.

Disruption of the murine procollagen C-proteinase enhancer 2 gene causes accumulation of pro-apoA-I and increased HDL levels.

Given the increased prevalence of cardiovascular disease in the world, the search for genetic variations that impact risk factors associated with the development of this disease continues. Multiple genetic association studies demonstrate that procollagen C-proteinase enhancer 2 (PCPE2) modulates HDL levels. Recent studies revealed an unexpected role for this protein in the proteolytic processing of pro-apolipoprotein (apo) A-I by enhancing the cleavage of the hexapeptide extension present at the N-terminus of apoA-I. To investigate the role of the PCPE2 protein in an in vivo model, PCPE2-deficient (PCPE2 KO) mice were examined, and a detailed characterization of plasma lipid profiles, apoA-I, HDL speciation, and function was done. Results of isoelectric focusing (IEF) electrophoresis together with the identification of the amino terminal peptides DEPQSQWDK and WHVWQQDEPQSQWDVK, representing mature apoA-I and pro-apoA-I, respectively, in serum from PCPE2 KO mice confirmed that PCPE2 has a role in apoA-I maturation. Lipid profiles showed a marked increase in plasma apoA-I and HDL-cholesterol (HDL-C) levels in PCPE2 KO mice compared with wild-type littermates, regardless of gender or diet. Changes in HDL particle size and electrophoretic mobility observed in PCPE2 KO mice suggest that the presence of pro-apoA-I impairs the maturation of HDL. ABCA1-dependent cholesterol efflux is defective in PCPE2 KO mice, suggesting that the functionality of HDL is altered.

Automated reporting of pharmacokinetic study results: gaining efficiency downstream from the laboratory.

The purpose of bioanalysis in the pharmaceutical industry is to provide 'raw' data about the concentration of a drug candidate and its metabolites as input for studies of drug properties such as pharmacokinetic (PK), toxicokinetic, bioavailability/bioequivalence and other studies. Building a seamless workflow from the laboratory to final reports is an ongoing challenge for IT groups and users alike. In such a workflow, PK automation can provide companies with the means to vastly increase the productivity of their scientific staff while improving the quality and consistency of their reports on PK analyses. This report presents the concept and benefits of PK automation and discuss which features of an automated reporting workflow should be translated into software requirements that pharmaceutical companies can use to select or build an efficient and effective PK automation solution that best meets their needs.

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.

Relationships of video assessments of touching and mouthing behaviors during outdoor play in urban residential yards to parental perceptions of child behaviors and blood lead levels.

Childrens' touching and mouthing behaviors during outdoor play in urban residential yards were measured using video observations. Descriptions were made of childrens' outdoor residential play environments. Behaviors assessed were used to examine (1) validity of parental responses to questions on childrens' oral behaviors and outdoor play and (2) relationships of mouthing behaviors to blood lead levels (BLLs). Thirty-seven children aged 1-5 years were recruited for 2 h of video recording in their yard and blood lead measurement. Video assessments included hourly rates of hand touches to ground/walking-level surfaces (cement/stone/steel, porch floor/steps, grass, and bare soil) and oral behaviors. Parental questionnaires assessed their child's outdoor activities, behaviors, and home environment. The children were: mean 39 months; 51% male; 89% Hispanic; and 78% Medicaid or uninsured. Twenty-two children had a blood lead measured (mean 6 microg/dl). During taping, all children had access to cement, 92% to grass, 73% to bare soil, and 59% to an open porch. Children had frequent touching and mouthing behaviors observed (median touches/h: touches to surfaces 81; hand-to-mouth area (with and without food) 26; hand-in-mouth 7; and object-in-mouth 17). Blood lead was directly correlated with log-transformed rates of hand-in-mouth (Pearson's correlation, r=0.564, n=22, P=0.006) and object-in-mouth (Pearson's correlation, r=0.482, n=22, P=0.023) behaviors. Parental questionnaire responses did not accurately reflect childrens' observed oral behaviors, play habits, or play environment. These data confirm the direct relationship between hand-to-mouth activities and BLLs and fail to validate parental perceptions of their child's mouthing behaviors or outdoor play environment.

Patients' refusal of surgery strongly impairs breast cancer survival.

OBJECTIVE: To compare patient and tumor characteristics and survival between women who refused and women who accepted surgery for breast cancer. SUMMARY BACKGROUND DATA: Surgery represents the central component of curative breast cancer treatment, but some women decide not to undergo surgery. Recent studies on the prognosis of non operated breast cancer are nonexistent. PATIENTS AND METHODS: This study included all 5339 patients aged < 80 years with nonmetastatic breast cancer recorded at the Geneva Cancer Registry between 1975 and 2000. We consulted the clinical files of all nonoperated women to identify those who refused surgery. Patients who refused surgery were compared with those accepting surgery using logistic regression. The effect of refusal of surgery on breast cancer mortality was evaluated by Cox proportional hazards analysis. RESULTS: Seventy patients (1.3%) refused surgery. These women were older, more frequently single, and had larger tumors. Overall, 37 (53%) women had no treatment, 25 (36%) hormone-therapy alone, and 8 (11%) other adjuvant treatments alone or in combination. Five-year specific breast cancer survival of women who refused surgery was lower than that of those who accepted (72%, 95% confidence interval, 60%-84% versus 87%, 95% confidence interval, 86%-88%, respectively). After accounting for other prognostic factors including tumor characteristics and stage, women who refused surgery had a 2.1-fold (95% confidence interval, 1.5-3.1) increased risk to die of breast cancer compared with operated women. CONCLUSIONS: Women who refuse surgery for breast cancer have a strongly impaired survival. This information might help patients who are hesitant toward surgery make a better informed decision.

Evaluation of landscape coverings to reduce soil lead hazards in urban residential yards: The Safer Yards Project.

This study was designed primarily to evaluate the effectiveness of landscape coverings to reduce the potential for exposure to lead-contaminated soil in an urban neighborhood. Residential properties were randomized in to three groups: application of ground coverings/barriers plus placement of a raised garden bed (RB), application of ground coverings/barriers only (no raised bed, NRB), and control. Outcomes evaluated soil lead concentration (employing a weighting method to assess acute hazard soil lead [areas not fully covered] and potential hazard soil lead [all soil surfaces regardless of covering status]), density of landscape coverings (6 = heavy, > 90% covered; 1 = bare, < 10% covered), lead tracked onto carpeted entryway floor mats, and entryway floor dust lead loadings. Over 1 year, the intervention groups had significantly reduced acute hazard soil lead concentration (median change: RB, -478 ppm; NRB, -698 ppm; control, +52 ppm; Kruskal-Wallis, P = 0.02), enhanced landscape coverings (mean change in score: RB, +0.6; NRB, +1.5; control, -0.6; ANOVA, P < 0.001), and a 50% decrease in lead tracked onto the floor mats. The potential hazard soil lead concentration and the entryway floor dust lead loading did not change significantly. Techniques evaluated by this study are feasible for use by property owners but will require continued maintenance. The long-term sustainability of the method needs further examination.

Association between CD62 ligand on naïve and memory T cells and history of cow's milk hypersensitivity in atopic patients.

BACKGROUND: Both IgE and non-IgE cell-mediated reactions can contribute to the immunopathogenesis of food hypersensitivity. OBJECTIVE: To study L-selectin expression in naïve (CD45RA+) and memory (CD45RO+) T cells in atopic patients with a history of cow's milk allergy and CD69 expression. METHODS: We evaluated 12 children with a history of cow's milk allergy. All 12 children underwent clinical history, examination, in vivo skin prick testing to inhalants and milk allergen, and in vitro radioallergosorbent testing for milk and total serum IgE levels. L-selectin levels on naive and memory T cells from patients and controls were analyzed by flow cytometry with fluorochrome-conjugated monoclonal antibodies after 4 hours or 7 days of incubation with medium alone, 1 microg/mL of pokeweed mitogen, or 50 microg/mL of casein. RESULTS: The percentage of CD45RA+ 62L+ cells with casein was 56% +/- 11% vs 38% +/- 7.7% in healthy controls (P < .009). The percentage of CD45RO- 62L+ cells was 22% +/- 7.1% vs 39% +/- 7.6% in healthy controls (P < .001), whereas the expression of CD62L+ in CD45RA+ and CD45RO+ cells decreased 149% +/- 33% vs 540% +/- 36% for healthy controls (P < .001) and 89% -+/- 16% vs 402% +/- 103% for healthy controls (P < .001), respectively. CONCLUSIONS: The results of the present study demonstrate the presence of CD62 ligand on naive and memory T cells, which might serve as a predictive marker for atopic dermatitis withother overlapping atopic disorders, such as asthma and allergic rhinitis.

Amplified Muc1-specific gene expression in colon cancer cells utilizing a binary system in adenoviral vectors.

Mucin-1 is expressed in a variety of colon carcinomas and Muc-1/DF3 promoters have been utilized to reduce systemic toxicity through specific gene expression. To overcome weak expression, which is much lower than the widely used cytomegalovirus-promoter (CMV), new adenoviral vectors containing a binary system of transgene amplification have been developed. The Muc-1/DF3 promoter was used to control the expression of a Gal4VP16 fusion protein. This vector also contained Gal4 binding sites enabling the fusion protein to act as a transactivator, inducing transgene expression within the same construct. Mucin-1 expression was analyzed in a variety of colon cancer cell lines. After infection with recombinant adenoviruses, transgene expression was quantified using the luciferase system. Integration of the Gal4VP16-binary resulted in an up to 250-fold increase of Muc-1/DF3-specific gene expression. In mucin-positive cell lines utilizing this amplified Muc-1/DF3 promoter, expression was up to 590-fold higher as compared to the CMV-promoter. Western blot detected the presence of Gal4VP16 in infected muc-1-positive but not-negative cell lines. These new adenoviral vectors combing highly efficient and specific transgene expression and will contribute to the safety and efficacy of experimental approaches in cancer gene therapy.