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Background: Adverse local tissue reaction (ALTR) is a recognized complication of total hip arthroplasty (THA) with metal-on-polyethylene (MoP) bearing surface implants. Specific models of THA implants have been identified as having a higher incidence of ALTR. The purpose of this study is to determine if serum metal levels, patient symptoms, implant factors, and imaging findings can be predictive of ALTR within this high-risk population. Methods: We retrospectively reviewed an observational cohort of 474 patients who underwent MoP THA and were at increased risk of having ALTR. Patients were stratified based on the presence or absence of ALTR. Patient symptoms, serum metal ions, implant head offset, and imaging findings were compared. Results: Patients with ALTR were more likely to be symptomatic (52.9% vs 9.9%, P < .0001). The presence of ALTR was associated with significantly higher serum cobalt and chromium levels (6.2 ppb vs 3.6 ppb, P < .0001; 2.3 ppb vs 1.2 ppb, P < .0001). Head offsets greater than 4 mm were associated with a higher prevalence of ALTR (53% vs 38%, P = .05). On metal artifact reduction sequence magnetic resonance imaging, patients with ALTR had larger effusions (4.7 cm vs 2.1 cm, P < .001) and a higher incidence of trochanteric bursitis (47% vs 16%, P < .001). Conclusions: In high-risk MoP implants, serum cobalt and chromium levels are elevated, even in patients without ALTR. A larger femoral head offset is a risk factor for the development of ALTR. Our study suggests that patients presenting with painful THA and elevated metal ions require risk stratification based on patient symptoms, metal artifact reduction sequence magnetic resonance imaging findings, and implant factors.

Background: The Core Curriculum Review Course in Cardiovascular and Thoracic Surgery is a 4-day educational program consisting of 77 didactic lectures that provide a comprehensive review of the material required for surgeons preparing for the American Board of Thoracic Surgery competency written examination. The lectures are supplemented with a written syllabus and interactive audience participation system. We sought to determine whether participation in this course could improve participants' performance on a cardiothoracic subject-based test. Methods: Sixty-five participants attended the 2018 course. Before beginning the course lectures, a multiple-choice pretest consisting of 77 questions was administered via mobile application to gauge the participants' baseline knowledge. A second multiple-choice posttest was made available beginning 7 weeks after the course, also by mobile application. Results: Twenty-nine participants completed both the pretest and the posttest. The median pretest score was 47% (36 of 77 correct answers). The median posttest score was 61% (47 of 77 correct answers), representing an increase of 14%. The Wilcoxon signed-rank test indicated a significant difference between the pretest and posttest scores (z = -4.36; P = .00). Overall, 25 participants (86%) improved their posttest score. Conclusions: The core curriculum review course was successful in improving participants' performance on the course tests, indicating that the participants' fund of knowledge was likely increased by attendance at the program. Additional strategies should be considered to address particular areas of study both for individual participants and for residents currently in training.

Objective:. To determine trends in internet search volume for elective surgery terms during the first peak of the coronavirus disease 2019 (COVID-19) pandemic using Google Trends data. Background:. Postponement of much-needed elective and urgent oncologic surgeries takes a toll on patients and the health care system. The COVID-19 pandemic has led to a decline in elective surgery volume, partially due to the cancellation of elective surgeries at the start of the pandemic. Methods:. We performed a cross-sectional analysis of internet search volume trends for elective surgery terms during the first peak of the COVID-19 pandemic using Google Trends data and compared to a control group of terms representing common urgent and oncologic surgeries. Results:. Search volume for elective surgery terms (“knee replacement,” “spinal fusion,” “hip replacement,” “laminectomy,” “cataract surgery”) revealed a decrease of up to 54% compared to the prepandemic period, a significantly greater decrease than search volume for urgent and oncologic surgery terms (“C-section,” “cholecystectomy,” “CABG,” “colectomy,” “lobectomy,” and “mastectomy”). Conclusions:. The first phase of the COVID-19 pandemic led to sharp declines in search volume for essential elective surgical procedures, which may have been partially due to the cancellation of elective surgeries, but patient factors such as a temporary decline in interest in elective surgery might have also played a role. Attention to internet search volume may be used during future public health crises to monitor public engagement and interest in important health topics, including preventive health measures such as cancer screening.

Background: Posthospital syndrome is associated with a decrease in physical and cognitive function and can contribute to overall patient decline. We can speculate on contributors to this decline (eg, poor sleep and nutrition), but other factors may also contribute. This study seeks to explain how patients experience hospitalization with particular attention on what makes the hospital stay difficult. Design: Qualitative interview study using grounded theory methodology. Setting: Single-site academic medical center. Patients: Hospitalized general medicine patients. Measurements: Interviews using a semistructured interview guide. Results: We recruited 20 general medicine inpatients from an academic medical center. Of the participants, 12 were women and the mean age was 55 years (range = 22-82 years). We found 4 major themes contributing to the hospital experience: (1) hospital environment (eg, food quality and entertainment), (2) patient factors (eg, indifference and expectations), (3) hospital personnel (eg, care team size and level of helpfulness), and (4) patient feelings (eg, level of control and feeling like an object). We discovered that these emotions arising from hospital experiences, together with the other 3 major themes, led to the patients’ perception of their hospital experience overall. We also explore the role that patient tolerance may play in the reporting of patient satisfaction. Conclusions: This article demonstrates the factors affecting how patients experience hospitalization. It provides insight into possible contributors to posthospital syndrome and offers a blueprint for specific quality improvement initiatives. Lastly, it briefly explores how patient tolerance may prove a challenge to the current system of quality reporting.

Category: Ankle Introduction/Purpose: Total ankle replacement (TAR) success has improved since first-generation implants, but patient satisfaction continues to be less than knee and hip replacements. Little is known about variations in distal tibia anatomy between genders and across ethnicities; therefore it is unclear the extent to which current TAR prostheses accommodate variability in patient size and shape. This study quantified distal tibia morphometrics relevant to TAR design, and assessed differences between ethnicities and genders. The hypotheses were: (1) The anterior-posterior (AP) location of the dwell point of the tibia is centralized; (2) The sagittal radius of curvature of the tibial articulation increases with bone size; (3) Differences in dwell point location or sagittal radii between genders and ethnicities can be attributed to size differences between those populations. Methods: Tibial CT scans were obtained from cadavers or individuals of various ethnicities (Table 1). Landmarks were defined on digital models created from the scans, including medial and lateral edges of the distal tibial articulation (Figure 1a), and sagittal contours of the articulation (Figure 1b). The articulation center was defined as the average center point of all contours (Figure 1c). The AP center and AP length at the level of a distal tibial resection for TAR were determined, and the AP offset of the articulation center was calculated (Figure 1c). Differences in metrics for each ethnic and gender group were determined using a one-way Anova (P< .05) with Tukey’s method for differentiating groups. Regression fits of AP offset, average medial radius, and average lateral radius were determined. Utilizing AP length as a covariate, ANCOVA was utilized to assess differences in AP offset and sagittal radii between gender and ethnic groups (P< .05). Results: Descriptive statistics for AP length, AP offset, and medial/lateral radii are shown in Table 1, with Tukey groupings assigned. The relationship between medial and lateral radius was not consistent across all groups. AP length was a significant covariate for medial and lateral radii, but not AP offset. The relationship between lateral radius and AP length was significantly impacted by ethnicity (P< .001), but not by gender (P=.067) (Figure 2a). Medial radius versus AP length was significantly impacted by both ethnicity (P=.01) and gender (P< .03) (Figure 2b). Conclusion: This study illustrates for the first time the complexity of anatomical variation of the distal tibia across ethnic groups and between genders. The location of the articulation center is invariant to tibia size across each ethnicity. Medial and lateral sagittal radii generally increase with bone size, but the relative radii of the medial and lateral compartments are not consistent across ethnicities. These results highlight the need for increased anatomic understanding of the distal tibia, and implications on TAR design and technique.

Treatment interference in children with acute and critical conditions is the conscious or unconscious, threatened or actual disrupting, dislodgment, or removal of the technological equipment/devices used for monitoring and/or treating such conditions. The purpose of this research was to explore the intervention strategies used by critical care nurses and parents as they attempted to maintain the technological interface and avoid treatment interference. Using an ethological approach, data were collected by observing and interviewing 18 children, ages 3 through 6 years, who were hospitalized in the pediatric intensive care unit (PICU) of a pediatric hospital located in the mid-Atlantic region, reviewing systematically their health care records, and interviewing their parents/legal guardians. Field notes were analyzed using a qualitative content analysis. Parents used psychosocial and physiologic strategies, as well as manual restraint, to avoid treatment interference. Nurses used psychosocial, physiologic, activities, and environmental strategies, in addition to physical restraint, to maintain the technological interface. [ABSTRACT FROM AUTHOR]

Background: Progressive enhancement predicted poor survival in ACRIN 6677/RTOG 0625, a multi-center trial of bevacizumab with irinotecan or temozolomide in recurrent glioblastoma, but pseudoresponse likely limited enhancement-based survival prognostication in T1 non-progressors. We aimed to determine whether early change in cerebral blood volume from baseline (ΔCBV) could further stratify the T1 non-progressors according to overall (OS) and progression-free (PFS) survival., Methods: 37/123 enrolled patients had DSC-MRI, including 13, 15, and 8 patients without 2D-T1 progression at 2, 8, and 16 weeks post-treatment initiation, respectively. Mean CBV normalized to white matter (nRCBV) and mean standardized CBV (sRCBV) were extracted from enhancing tumor. ROC curves were derived for ΔCBV using six-month PFS and one-year OS as reference standards. Kaplan-Meier survival estimates and log-rank test compared PFS and OS for both ΔCBV (increase vs. decrease) and T1 response status (stable vs. decreasing enhancement)., Results: PFS and OS were significantly worse for increasing CBV at 2 weeks (p=0.003 and p=0.002 for nRCBV, and p=0.03 and p=0.03 for sRCBV, respectively), but not for 2D-T1 patients with stable vs. decreasing enhancement (p=0.44 and p=0.86, respectively). ΔCBV at week 2 was also a good prognostic marker for OS-1 and PFS-6 using ROC analysis. By contrast, 2D-T1 response status at weeks 2, 8, and 16 was not associated with PFS-6. ΔCBV at 16 weeks (p=0.008 for sRCBV) but not 8 weeks (p=0.74 for nRCBV and p=0.56 for sRCBV) was associated with significant difference in median survival, but no difference in survival was observed for 2D-T1 patients with stable vs. decreasing enhancement at 8 weeks (p=0.69) or 16 weeks (p=0.21). At 16 weeks, OS did not differ significantly between 2D-T1 progressors and 2D-T1 non-progressors with increasing CBV (median survival 3.3 months post week 16 scan vs. 9.2 months, respectively; p=0.13), suggesting that 2D-T1 non-progressors with increasing CBV may have a prognosis like that of 2D-T1 progressors., Conclusion: After 2 weeks of anti-angiogenic therapy, ΔCBV in 2D-T1 non-progressors significantly prognosticated PFS and OS, whereas 2D-T1 response status did not, identifying a subpopulation that benefits from bevacizumab. Combining 2D-T1 progression and ΔCBV may yield a response assessment paradigm with 3-tiered OS stratification., Competing Interests: Author JB is a paid consultant for Neosoma, Inc. Author KS has ownership interest in IQ-AI Ltd and financial interest in Imaging Biometrics LLC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Boxerman, Snyder, Barboriak and Schmainda.)

Background: Uncertainty regarding the reproducibility of the apparent diffusion coefficient (ADC) hampers the use of quantitative diffusion-weighted imaging (DWI) in evaluation of the prostate with magnetic resonance imaging MRI. The quantitative imaging biomarkers alliance (QIBA) profile for quantitative DWI claims a within-subject coefficient of variation (wCV) for prostate lesion ADC of 0.17. Improved understanding of ADC reproducibility would aid the use of quantitative diffusion in prostate MRI evaluation., Purpose: Evaluation of the repeatability (same-day) and reproducibility (multi-day) of whole-prostate and focal-lesion ADC assessment in a multi-site setting., Study Type: Prospective multi-institutional., Subjects: Twenty-nine males, ages 53 to 80 (median 63) years, following diagnosis of prostate cancer, 10 with focal lesions., Field Strength/sequence: 3T, single-shot spin-echo diffusion-weighted echo-planar sequence with four b-values., Assessment: Sites qualified for the study using an ice-water phantom with known ADC. Readers performed DWI analyses at visit 1 ("V1") and visit 2 ("V2," 2-14 days after V1), where V2 comprised scans before ("V2pre") and after ("V2post") a "coffee-break" interval with subject removal and repositioning. A single reader segmented the whole prostate. Two readers separately placed region-of-interests for focal lesions., Statistical Tests: Reproducibility and repeatability coefficients for whole prostate and focal lesions derived from median pixel ADC. We estimated the wCV and 95% confidence interval using a variance stabilizing transformation and assessed interreader reliability of focal lesion ADC using the intraclass correlation coefficient (ICC)., Results: The ADC biases from b 0 -b 600 and b 0 -b 800 phantom scans averaged 1.32% and 1.44%, respectively; mean b-value dependence was 0.188%. Repeatability and reproducibility of whole prostate median pixel ADC both yielded wCVs of 0.033 (N = 29). In 10 subjects with an evaluable focal lesion, the individual reader wCVs were 0.148 and 0.074 (repeatability) and 0.137 and 0.078 (reproducibility). All time points demonstrated good to excellent interreader reliability for focal lesion ADC (ICC V1  = 0.89; ICC V2pre  = 0.76; ICC V2post  = 0.94)., Data Conclusion: This study met the QIBA claim for prostate ADC. Test-retest repeatability and multi-day reproducibility were largely equivalent. Interreader reliability for focal lesion ADC was high across time points., Level of Evidence: 1 TECHNICAL EFFICACY: Stage 2 TOC CATEGORY: Pelvis., (© 2022 International Society for Magnetic Resonance in Medicine.)

Importance: Guiding treatment decisions for women with ductal carcinoma in situ (DCIS) requires understanding patient preferences and the influence of preoperative magnetic resonance imaging (MRI) and surgeon recommendation., Objective: To identify factors associated with surgery preference and surgery receipt among a prospective cohort of women with newly diagnosed DCIS., Design, Setting, and Participants: A prospective cohort study was conducted at 75 participating institutions, including community practices and academic centers, across the US between March 25, 2015, and April 27, 2016. Data were analyzed from August 2 to September 24, 2021. This was an ancillary study of the ECOG-ACRIN Cancer Research Group (E4112). Women with recently diagnosed unilateral DCIS who were eligible for wide local excision and had a diagnostic mammogram within 3 months of study registration were included. Participants who had documented surgery and completed the baseline patient-reported outcome questionnaires were included in this substudy., Exposures: Women received preoperative MRI and surgeon consultation and then underwent wide local excision or mastectomy. Participants will be followed up for recurrence and overall survival for 10 years from the date of surgery., Main Outcomes and Measures: Patient-reported outcome questionnaires assessed treatment goals and concerns and surgery preference before MRI and after MRI and surgeon consultation., Results: Of the 368 participants enrolled 316 (86%) were included in this substudy (median [range] age, 59.5 [34-87] years; 45 women [14%] were Black; 245 [78%] were White; and 26 [8%] were of other race). Pre-MRI, age (odds ratio [OR] per 5-year increment, 0.45; 95% CI, 0.26-0.80; P = .007) and the importance of keeping one's breast (OR, 0.48; 95% CI, 0.31-0.72; P < .001) vs removal of the breast for peace of mind (OR, 1.35; 95% CI, 1.04-1.76; P = .03) were associated with surgery preference for mastectomy. After MRI and surgeon consultation, MRI upstaging (48 of 316 [15%]) was associated with patient preference for mastectomy (OR, 8.09; 95% CI, 2.51-26.06; P < .001). The 2 variables with the highest ORs for initial receipt of mastectomy were MRI upstaging (OR, 12.08; 95% CI, 4.34-33.61; P < .001) and surgeon recommendation (OR, 4.85; 95% CI, 1.99-11.83; P < .001)., Conclusions and Relevance: In this cohort study, change in patient preference for DCIS surgery and surgery received were responsive to MRI results and surgeon recommendation. These data highlight the importance of ensuring adequate information and ongoing communication about the clinical significance of MRI findings and the benefits and risks of available treatment options.

Importance: The use of magnetic resonance imaging (MRI) in pretreatment planning of ductal carcinoma in situ (DCIS) remains controversial. Understanding changes in short-term health-related quality of life associated with breast MRI would allow for a more complete comparative effectiveness assessment., Objective: To assess whether there are changes in patient-reported quality of life associated with breast MRI among women diagnosed with DCIS., Design, Setting, and Participants: This cohort study was a substudy of a nonrandomized clinical trial conducted at 75 participating US institutions from March 2015 to April 2016. Women recently diagnosed with unilateral DCIS who were eligible for wide local excision and had a diagnostic mammogram within 3 months of study registration were included. A total of 355 women met the eligibility criteria and underwent the study MRI. Data analysis was performed from June 3, 2020, to July 1, 2021., Exposures: Participants underwent bilateral breast MRI within 30 days of study registration and before surgery. Information on patient-reported testing burden for breast MRI was collected after MRI and before surgery., Main Outcomes and Measures: The primary outcome of this substudy was the patient-reported testing burden of breast MRI, measured by the Testing Morbidities Index (TMI) summated scale score. The TMI is a 7-item instrument that evaluates the temporary changes in quality of life associated with imaging before, during, and after the test (0 represents the worst possible, 100 the hypothetical ideal test experience)., Results: Of the 355 women who met the eligibility criteria, 244 (69%) completed both questionnaires and were included in this analysis. The median age was 59 years (range, 34-85 years). The mean MRI TMI summated scale score was 85.9 (95% CI, 84.6-87.3). Of the 244 women, 142 (58%) experienced at least some fear and anxiety before the examination, and 120 women (49%) experienced fear and anxiety during the examination. A total of 156 women (64%) experienced pain or discomfort during the examination. In multivariable analyses, greater test-related burden was associated with higher levels of cancer worry (regression coefficient, -2.75; SE, 0.94; P = .004)., Conclusions and Relevance: In this cohort study, a clinically meaningful breast MRI testing burden among women with DCIS was revealed that was significantly associated with cancer worry. Understanding the potential quality-of-life reduction associated with MRI, especially when used in combination with mammography, may allow development of targeted interventions to improve the patient experience.

We measured changes in 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT) images in the lung parenchyma to quantify the degree of lung inflammation in patients with locally advanced non-small cell lung cancer (NSCLC) who received radiotherapy (RT). The goal of this study was to demonstrate successful implementation of this imaging methodology on NSCLC patients and to report quantitative statistics between pre-RT and post-RT. Seventy-one patients with NSCLC underwent FDG-PET/CT imaging before and after RT in a prospective study (ACRIN 6668/RTOG 0235). Comparisons between pre-RT and post-RT PET/CT were conducted for partial volume corrected (PVC)-mean standardized uptake value (SUVmean), PVC-global lung parenchymal glycolysis (GLPG), and lung volume for both ipsilateral and contralateral lungs using the nonparametric Wilcoxon signed-rank test. Regression modeling was conducted to associate clinical characteristics with post-RT PET/CT parameters. There was a significant increase in average SUVmean and GLPG of the ipsilateral lung (relative change 40% and 20%) between pre-RT and post-RT PET/CT scans (P<0.0001 and P=0.004). Absolute increases in PVC-SUVmean and PVC-GLPG were more pronounced (ΔPVC-SUVmean 0.32 versus ΔSUVmean 0.28; ΔPVC-GLPG 463.34 cc versus ΔGLPG 352.90 cc) and highly significant (P<0.0001). In contrast, the contralateral lung demonstrated no significant difference between pre-RT to post-RT in either GLPG (P=0.12) or SUVmean (P=0.18). The only clinical feature significantly associated with post-RT PET/CT parameters was clinical staging. Our study demonstrated inflammatory response in the ipsilateral lung of NSCLC patients treated with photon RT, suggesting that PET/CT parameters may serve as biomarkers for radiation pneumonitis (RP)., Competing Interests: None., (AJNMMI Copyright © 2021.)

Background There are limited data from clinical trials describing preoperative MRI features and performance in the evaluation of mammographically detected ductal carcinoma in situ (DCIS). Purpose To report qualitative MRI features of DCIS, MRI performance in the identification of additional disease, and associations of imaging features with pathologic, genomic, and surgical outcomes from the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) E4112 trial. Materials and Methods Secondary analyses of a multicenter prospective clinical trial from the ECOG-ACRIN Cancer Research Group included women with DCIS diagnosed with conventional imaging techniques (mammography and US), confirmed via core-needle biopsy (CNB), and enrolled between March 2015 and April 2016 who were candidates for wide local excision (WLE) based on conventional imaging and clinical examination results. DCIS MRI features and pathologic features from CNB and excision were recorded. Each woman without invasive upgrade of the index DCIS at WLE received a 12-gene DCIS score. MRI performance metrics were calculated. Associations of imaging features with invasive upgrade, dichotomized DCIS score (<39 vs ≥39), and single WLE success were estimated in uni- and multivariable analyses. Results Among 339 women (median age, 60 years; interquartile range, 51-66 years), most DCIS cases showed nonmass enhancement (NME) (195 of 339 [58%]) on MRI scans with larger median size than on mammograms (19 mm vs 12 mm; P < .001). Positive predictive value of MRI-prompted CNBs was 32% (21 of 66) (95% CI: 22, 44), yielding an additional cancer detection rate of 6.2% (21 of 339) (95% CI: 4.1, 9.3). MRI false-positive rate was 14.2% (45 of 318) (95% CI: 10.7, 18.4). No imaging features were associated with invasive upgrade or DCIS score ( P = .05 to P = .95). Smaller size and focal NME distribution at MRI were linked to single WLE success ( P < .001). Conclusion Preoperative MRI depicted ductal carcinoma in situ (DCIS) diagnosed with conventional imaging most commonly as nonmass enhancement, with larger median span than mammography, and additional cancer detection rate of 6.2%. MRI features of this subset of DCIS did not enable prediction of pathologic or genomic outcomes. Clinical trial registration no. NCT02352883 © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Kuhl in this issue. An earlier incorrect version of this article appeared online. This article was corrected on August 4, 2021.

Background The RESCUE (Randomized Evaluation of Patients with Stable Angina Comparing Utilization of Noninvasive Examinations) trial was a randomized, controlled, multicenter, comparative efficacy outcomes trial designed to assess whether initial testing with coronary computed tomographic angiography (CCTA) is noninferior to single photon emission computed tomography (SPECT) myocardial perfusion imaging in directing patients with stable angina to optimal medical therapy alone or optimal medical therapy with revascularization. Methods and Results The end point was first major adverse cardiovascular event (MACE) (cardiac death or myocardial infarction), or revascularization. Noninferiority margin for CCTA was set a priori as a hazard ratio (HR) of 1.3 (95% CI=0, 1.605). One thousand fifty participants from 44 sites were randomized to CCTA (n=518) or SPECT (n=532). Mean follow-up time was 16.2 (SD 7.9) months. There were no cardiac-related deaths. In patients with a negative CCTA there was 1 acute myocardial infarction; in patients with a negative SPECT examination there were 2 acute myocardial infarctions; and for positive CCTA and SPECT, 1 acute myocardial infarction each. Participants in the CCTA arm had a similar rate of MACE or revascularization compared with those in the SPECT myocardial perfusion imaging arm, (HR, 1.03; 95% CI=0.61-1.75) ( P =0.19). CCTA segment involvement by a stenosis of ≥50% diameter was a better predictor of MACE and revascularization at 1 year ( P =0.02) than the percent reversible defect size by SPECT myocardial perfusion imaging. Four (1.2%) patients with negative CCTA compared with 14 (3.2%) with negative SPECT had MACE or revascularization ( P =0.03). Conclusions There was no difference in outcomes of patients who had stable angina and who underwent CCTA in comparison to SPECT as the first imaging test directing them to optimal medical therapy alone or with revascularization. CCTA was a better predictor of MACE and revascularization. Registration Information URL: https://www.clinicaltrials.gov/. Identifier: NCT01262625.

Importance: Improved screening methods for women with dense breasts are needed because of their increased risk of breast cancer and of failed early diagnosis by screening mammography., Objective: To compare the screening performance of abbreviated breast magnetic resonance imaging (MRI) and digital breast tomosynthesis (DBT) in women with dense breasts., Design, Setting, and Participants: Cross-sectional study with longitudinal follow-up at 48 academic, community hospital, and private practice sites in the United States and Germany, conducted between December 2016 and November 2017 among average-risk women aged 40 to 75 years with heterogeneously dense or extremely dense breasts undergoing routine screening. Follow-up ascertainment of cancer diagnoses was complete through September 12, 2019., Exposures: All women underwent screening by both DBT and abbreviated breast MRI, performed in randomized order and read independently to avoid interpretation bias., Main Outcomes and Measures: The primary end point was the invasive cancer detection rate. Secondary outcomes included sensitivity, specificity, additional imaging recommendation rate, and positive predictive value (PPV) of biopsy, using invasive cancer and ductal carcinoma in situ (DCIS) to define a positive reference standard. All outcomes are reported at the participant level. Pathology of core or surgical biopsy was the reference standard for cancer detection rate and PPV; interval cancers reported until the next annual screen were included in the reference standard for sensitivity and specificity., Results: Among 1516 enrolled women, 1444 (median age, 54 [range, 40-75] years) completed both examinations and were included in the analysis. The reference standard was positive for invasive cancer with or without DCIS in 17 women and for DCIS alone in another 6. No interval cancers were observed during follow-up. Abbreviated breast MRI detected all 17 women with invasive cancer and 5 of 6 women with DCIS. Digital breast tomosynthesis detected 7 of 17 women with invasive cancer and 2 of 6 women with DCIS. The invasive cancer detection rate was 11.8 (95% CI, 7.4-18.8) per 1000 women for abbreviated breast MRI vs 4.8 (95% CI, 2.4-10.0) per 1000 women for DBT, a difference of 7 (95% CI, 2.2-11.6) per 1000 women (exact McNemar P = .002). For detection of invasive cancer and DCIS, sensitivity was 95.7% (95% CI, 79.0%-99.2%) with abbreviated breast MRI vs 39.1% (95% CI, 22.2%-59.2%) with DBT (P = .001) and specificity was 86.7% (95% CI, 84.8%-88.4%) vs 97.4% (95% CI, 96.5%-98.1%), respectively (P < .001). The additional imaging recommendation rate was 7.5% (95% CI, 6.2%-9.0%) with abbreviated breast MRI vs 10.1% (95% CI, 8.7%-11.8%) with DBT (P = .02) and the PPV was 19.6% (95% CI, 13.2%-28.2%) vs 31.0% (95% CI, 17.0%-49.7%), respectively (P = .15)., Conclusions and Relevance: Among women with dense breasts undergoing screening, abbreviated breast MRI, compared with DBT, was associated with a significantly higher rate of invasive breast cancer detection. Further research is needed to better understand the relationship between screening methods and clinical outcome., Trial Registration: ClinicalTrials.gov Identifier: NCT02933489.

Importance: Advanced diagnostics, such as magnetic resonance imaging (MRI) and gene expression profiles, are potentially useful to guide targeted treatment in patients with ductal carcinoma in situ (DCIS)., Objectives: To examine the proportion of patients who converted to mastectomy after MRI and the reasons for those conversions and to measure patient adherence to radiotherapy guided by the 12-gene DCIS score., Design, Setting, and Participants: Analysis of a prospective, cohort, nonrandomized clinical trial that enrolled women with DCIS on core biopsy who were candidates for wide local excision (WLE) from 75 institutions from March 25, 2015, to April 27, 2016, through the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network trial E4112., Interventions: Participants underwent breast MRI before surgery, and subsequent management incorporated MRI findings for choice of surgery. The DCIS score was used to guide radiotherapy recommendations among women with DCIS who had WLE as the final procedure and had tumor-free excision margins of 2 mm or greater., Main Outcomes and Measures: The primary end point was to estimate the conversion rate to mastectomy and the reason for conversion., Results: Of 339 evaluable women (mean [SD] age, 59.1 [10.1] years; 262 [77.3%] of European descent) eligible for WLE before MRI, 65 (19.2%; 95% CI, 15.3%-23.7%) converted to mastectomy. Of these 65 patients, conversion was based on MRI findings in 25 (38.5%), patient preference in 25 (38.5%), positive margins after attempted WLE in 10 (15.4%), positive genetic test results in 3 (4.6%), and contraindication to radiotherapy in 2 (3.1%). Among the 285 who had WLE performed after MRI as the first surgical procedure, 274 (96.1%) achieved successful breast conservation. Of 171 women eligible for radiotherapy guided by DCIS score (clear margins, absence of invasive disease, and score obtained), the score was low (<39) in 82 (48.0%; 95% CI, 40.6%-55.4%) and intermediate-high (≥39) in 89 (52.0%; 95% CI, 44.6%-59.4%). Of these 171 patients, 159 (93.0%) were adherent with recommendations., Conclusions and Relevance: Among women with DCIS who were WLE candidates based on conventional imaging, multiple factors were associated with conversion to mastectomy. This study may provide useful preliminary information required for designing a planned randomized clinical trial to determine the effect of MRI and DCIS score on surgical management, radiotherapy, overall resource use, and clinical outcomes, with the ultimate goal of achieving greater therapeutic precision., Trial Registration: ClinicalTrials.gov identifier: NCT02352883.

Background and Purpose: Brain tumor clinical trials requiring solid tumor assessment typically rely on the 2D manual delineation of enhancing tumors by ≥2 expert readers, a time-consuming step with poor interreader agreement. As a solution, we developed quantitative dT1 maps for the delineation of enhancing lesions. This retrospective analysis compares dT1 with 2D manual delineation of enhancing tumors acquired at 2 time points during the post therapeutic surveillance period of the American College of Radiology Imaging Network 6677/Radiation Therapy Oncology Group 0625 (ACRIN 6677/RTOG 0625) clinical trial., Materials and Methods: Patients enrolled in ACRIN 6677/RTOG 0625, a multicenter, randomized Phase II trial of bevacizumab in recurrent glioblastoma, underwent standard MR imaging before and after treatment initiation. For 123 patients from 23 institutions, both 2D manual delineation of enhancing tumors and dT1 datasets were evaluable at weeks 8 ( n = 74) and 16 ( n = 57). Using dT1, we assessed the radiologic response and progression at each time point. Percentage agreement with adjudicated 2D manual delineation of enhancing tumor reads and association between progression status and overall survival were determined., Results: For identification of progression, dT1 and adjudicated 2D manual delineation of enhancing tumor reads were in perfect agreement at week 8, with 73.7% agreement at week 16. Both methods showed significant differences in overall survival at each time point. When nonprogressors were further divided into responders versus nonresponders/nonprogressors, the agreement decreased to 70.3% and 52.6%, yet dT1 showed a significant difference in overall survival at week 8 ( P = .01), suggesting that dT1 may provide greater sensitivity for stratifying subpopulations., Conclusions: This study shows that dT1 can predict early progression comparable with the standard method but offers the potential for substantial time and cost savings for clinical trials., (© 2019 by American Journal of Neuroradiology.)

Objectives: Vancomycin weight-based dosing regimens often fail to achieve therapeutic trough serum concentration in children ≤12 years of age and rigorous studies evaluating efficacy and safety of body surface area (BSA)-based dosing regimens have not been performed. We compared vancomycin trough serum concentrations in pediatric patients receiving a weight- or BSA-based dosing regimen., Methods: This was a single-center, retrospective study evaluating pediatric patients, ages 1 to 12 years, who received vancomycin from September 2012 to October 2015. Patients received a minimum of 3 consecutive doses at the same scheduled interval within a dosing regimen prior to a measured vancomycin serum trough concentration. The primary outcome was percentage of initial vancomycin trough concentrations ≥10 mg/L. The secondary outcomes were percentage of supratherapeutic, therapeutic, and subtherapeutic vancomycin serum concentration for all patients, including a subset of overweight and obese patients, and number of nephrotoxic occurrences., Results: BSA-based dosing regimens resulted in 50% of the initial vancomycin trough concentrations ≥ 10 mg/L compared with 17% for the weight-based dosing regimens (p < 0.0001). No statistically significant differences were noted between the 2 dosing regimens for supratherapeutic, therapeutic, or subtherapeutic trough concentrations for all patients, and for the subset of overweight and obese patients. Nephrotoxic occurrences were noted in 7% of the weight-based dosing regimens compared with none in the BSA-based dosing regimens., Conclusions: A BSA-based vancomycin dosing regimen resulted in significantly more initial vancomycin trough concentrations ≥10 mg/L and trended towards higher initial vancomycin trough concentrations without observable nephrotoxicity., Competing Interests: Disclosure The authors declare no conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria. Beth Sawrey and Mary Subramanian have full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Purpose To evaluate factors contributing to interreader variation (IRV) in parameters measured at dynamic contrast material-enhanced (DCE) MRI in patients with glioblastoma who were participating in a multicenter trial. Materials and Methods A total of 18 patients (mean age, 57 years ± 13 [standard deviation]; 10 men) who volunteered for the advanced imaging arm of ACRIN 6677, a substudy of the RTOG 0625 clinical trial for recurrent glioblastoma treatment, underwent analyzable DCE MRI at one of four centers. The 78 imaging studies were analyzed centrally to derive the volume transfer constant (K trans ) for gadolinium between blood plasma and tissue extravascular extracellular space, fractional volume of the extracellular extravascular space (v e ), and initial area under the gadolinium concentration curve (IAUGC). Two independently trained teams consisting of a neuroradiologist and a technologist segmented the enhancing tumor on three-dimensional spoiled gradient-recalled acquisition in the steady-state images. Mean and median parameter values in the enhancing tumor were extracted after registering segmentations to parameter maps. The effect of imaging time relative to treatment, map quality, imager magnet and sequence, average tumor volume, and reader variability in tumor volume on IRV was studied by using intraclass correlation coefficients (ICCs) and linear mixed models. Results Mean interreader variations (± standard deviation) (difference as a percentage of the mean) for mean and median IAUGC, mean and median K trans , and median v e were 18% ± 24, 17% ± 23, 27% ± 34, 16% ± 27, and 27% ± 34, respectively. ICCs for these metrics ranged from 0.90 to 1.0 for baseline and from 0.48 to 0.76 for posttreatment examinations. Variability in reader-derived tumor volume was significantly related to IRV for all parameters. Conclusion Differences in reader tumor segmentations are a significant source of interreader variation for all dynamic contrast-enhanced MRI parameters. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Wolf in this issue.

Background The role of arterial load in severe aortic stenosis is increasingly recognized. However, patterns of pulsatile load and their implications in this population are unknown. We aimed to assess the relationship between the arterial properties and both (1) left ventricular remodeling and fibrosis and (2) the clinical course of patients with severe aortic stenosis undergoing aortic valve replacement ( AVR ). Methods and Results We enrolled 38 participants with symptomatic severe aortic stenosis scheduled to undergo surgical AVR . Aortic root characteristic impedance, wave reflections parameters (reflection magnitude, reflected wave transit time), and myocardial extracellular mass were measured with cardiac magnetic resonance imaging and arterial tonometry Cardiac magnetic resonance imaging was repeated at 6 months in 30 participants. A reduction in cellular mass (133.6 versus 113.9 g; P=0.002) but not extracellular mass (42.3 versus 40.6 g; P=0.67) was seen after AVR . Participants with higher extracellular mass exhibited greater reflection magnitude (0.68 versus 0.54; P=0.006) and lower aortic root characteristic impedance (56.3 versus 96.9 dynes/s per cm 5 ; P=0.006). Reflection magnitude was a significant predictor of smaller improvement in the quality of life (Kansas City Cardiomyopathy Questionnaire score) after AVR ( R=-0.51; P=0.0026). The 6-minute walk distance at 6 months after AVR was positively correlated with the reflected wave transit time ( R=0.52; P=0.01). Conclusions Consistent with animal studies, arterial wave reflections are associated with interstitial volume expansion in severe aortic stenosis and predict a smaller improvement in quality of life following AVR . Future trials should assess whether wave reflections represent a potential therapeutic target to mitigate myocardial interstitial remodeling and to improve the clinical status of this patient population.

Ideally, neoadjuvant chemotherapy (NAC) assessment should predict pathologic complete response (pCR), a surrogate clinical endpoint for 5-year survival, as early as possible during typical 3- to 6-month breast cancer treatments. We introduce and demonstrate an approach for predicting pCR within 10 days of initiating NAC. The method uses a bedside diffuse optical spectroscopic imaging (DOSI) technology and logistic regression modeling. Tumor and normal tissue physiological properties were measured longitudinally throughout the course of NAC in 33 patients enrolled in the American College of Radiology Imaging Network multicenter breast cancer DOSI trial (ACRIN-6691). An image analysis scheme, employing z-score normalization to healthy tissue, produced models with robust predictions. Notably, logistic regression based on z-score normalization using only tissue oxygen saturation (StO2) measured within 10 days of the initial therapy dose was found to be a significant predictor of pCR (AUC  =  0.92; 95% CI: 0.82 to 1). This observation suggests that patients who show rapid convergence of tumor tissue StO2 to surrounding tissue StO2 are more likely to achieve pCR. This early predictor of pCR occurs prior to reductions in tumor size and could enable dynamic feedback for optimization of chemotherapy strategies in breast cancer.

Purpose: In recent years, multiple studies have demonstrated the value of volumetric FDG-PET/CT parameters as independent prognostic factors in patients with non-small cell lung cancer (NSCLC). We aimed to determine the optimal cut-off points of pretreatment volumetric FDG-PET/CT parameters in predicting overall survival (OS) in patients with locally advanced NSCLC and to recommend imaging biomarkers appropriate for routine clinical applications., Methods: Patients with inoperable stage IIB/III NSCLC enrolled in ACRIN 6668/RTOG 0235 were included. Pretreatment FDG-PET scans were quantified using semiautomatic adaptive contrast-oriented thresholding and local-background partial-volume-effect-correction algorithms. For each patient, the following indices were measured: metabolic tumor volume (MTV), total lesion glycolysis (TLG), SUVmax, SUVmean, partial-volume-corrected TLG (pvcTLG), and pvcSUVmean for the whole-body, primary tumor, and regional lymph nodes. The association between each index and patient outcome was assessed using Cox proportional hazards regression. Optimal cut-off points were estimated using recursive binary partitioning in a conditional inference framework and used in Kaplan-Meier curves with log-rank testing. The discriminatory ability of each index was examined using time-dependent receiver operating characteristic (ROC) curves and corresponding area under the curve (AUC(t))., Results: The study included 196 patients. Pretreatment whole-body and primary tumor MTV, TLG, and pvcTLG were independently prognostic of OS. Optimal cut-off points were 175.0, 270.9, and 35.5 cm 3 for whole-body TLG, pvcTLG, and MTV, and were 168.2, 239.8, and 17.4 cm 3 for primary tumor TLG, pvcTLG, and MTV, respectively. In time-dependent ROC analysis, AUC(t) for MTV and TLG were uniformly higher than that of SUV measures over all time points. Primary tumor and whole-body parameters demonstrated similar patterns of separation for those patients above versus below the optimal cut-off points in Kaplan-Meier curves and in time-dependent ROC analysis., Conclusion: We demonstrated that pretreatment whole-body and primary tumor volumetric FDG-PET/CT parameters, including MTV, TLG, and pvcTLG, are strongly prognostic for OS in patients with locally advanced NSCLC, and have similar discriminatory ability. Therefore, we believe that, after validation in future trials, the derived optimal cut-off points for primary tumor volumetric FDG-PET/CT parameters, or their more refined versions, could be incorporated into routine clinical practice, and may provide more accurate prognostication and staging based on tumor metabolic features.

Objective: We sought to derive and validate a model for identifying suspected ACS patients harboring undiagnosed significant coronary artery disease (CAD)., Methods: This was a secondary analysis of data from a randomized control trial (RCT). Patients randomized to the CTA arm of an RCT examining a CTA-based strategy for ruling-out acute coronary syndrome (ACS) constitute the derivation cohort, which was randomly divided into a training dataset (2/3, used for model derivation) and a test dataset (1/3, used for internal validation (IV)). ED patients from a different center receiving CTA to evaluate for suspected ACS constitute the external validation (EV) cohort. Primary outcome was CTA-assessed significant CAD (stenosis of ≥50% in a major coronary artery)., Results: In the derivation cohort, 11.2% (76/679) of subjects had CTA-assessed significant CAD, and in the EV cohort, 8.2% of subjects (87/1056) had CTA-assessed significant CAD. Age was the strongest predictor of significant CAD among the clinical risk factors examined. Predictor variables included in the derived logistic regression model were: age, sex, tobacco use, diabetes, and race. This model exhibited an area under the receiver operating characteristic curve (ROC AUC) of 0.72 (95% CI: 0.61-0.83) based on IV, and 0.76 (95% CI: 0.70, 0.82) based on EV. The derived random forest model based on clinical risk factors yielded improved but not sufficient discrimination of significant CAD (ROC AUC = 0.76 [95% CI: 0.67-0.85] based on IV). Coronary artery calcium score was a more accurate predictor of significant CAD than any combination of clinical risk factors (ROC AUC = 0.85 [95% CI: 0.76-0.94] based on IV; ROC AUC = 0.92 [95% CI: 0.88-0.95] based on EV)., Conclusions: Clinical risk factors, either individually or in combination, are insufficient for accurately identifying suspected ACS patients harboring undiagnosed significant coronary artery disease., (Copyright © 2017 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine whether higher pre-treatment metabolic tumor volume (tMTV-pre) is associated with worse overall survival (OS) in patients with inoperable NSCLC treated with definitive chemoradiation (CRT)., Methods: This is a secondary analysis of the American College of Radiology Imaging Network (ACRIN) 6668/Radiation Therapy Oncology Group 0235 trial. Pre-treatment PET scans were performed on ACRIN-qualified scanners. Computer-aided MTV measurement was performed using RT&#95;Image. Kaplan-Meier curves and Cox proportional hazards regression models were used to assess the association between tMTV and OS., Results: Of the 250 patients enrolled on the study, 230 were evaluable for tMTV-pre. Patients with MTV-pre >32 mL (median value) vs. ≤32 mL had worse median OS (14.8 vs. 29.7 months, p < 0.001). As a continuous variable, higher tMTV-pre (per 10-mL increase) remained associated with worse OS (HR = 1.03, p < 0.001) after controlling for other variables. A significant interaction between radiation dose and tMTV-pre occurred for OS (p = 0.002), demonstrating that the negative prognostic impact of tMTV-pre decreased as radiotherapy dose increased. Among patients with tMTV-pre ≤32 mL, there was no difference in survival according to radiotherapy dose delivered (p = 0.694). However, median OS was inferior in patients with tMTV-pre >32 mL who received ≤60 Gy compared with those who received 61-69 Gy or ≥70 Gy (p = 0.001)., Conclusions: Higher tMTV-pre is associated with significantly worse OS in inoperable stage III NSCLC treated with definitive CRT. Our findings suggest that for patients with large tMTV-pre, achieving a therapeutic radiation dose may help maximize OS. Prospective studies are needed to confirm this finding.

The prospective multicenter ACRIN 6691 trial was designed to evaluate whether changes from baseline to mid-therapy in a diffuse optical spectroscopic imaging (DOSI)-derived imaging endpoint, the tissue optical index (TOI), predict pathologic complete response (pCR) in women undergoing breast cancer neoadjuvant chemotherapy (NAC). DOSI instruments were constructed at the University of California, Irvine (Irvine, CA), and delivered to six institutions where 60 subjects with newly diagnosed breast tumors (at least 2 cm in the longest dimension) were enrolled over a 2-year period. Bedside DOSI images of the tissue concentrations of deoxy-hemoglobin (ctHHb), oxy-hemoglobin (ctHbO 2 ), water (ctH 2 O), lipid, and TOI (ctHHb × ctH 2 O/lipid) were acquired on both breasts up to four times during NAC treatment: baseline, 1-week, mid-point, and completion. Of the 34 subjects (mean age 48.4 ± 10.7 years) with complete, evaluable data from both normal and tumor-containing breast, 10 (29%) achieved pCR as determined by central pathology review. The percent change in tumor-to-normal TOI ratio (%TOI TN ) from baseline to mid-therapy ranged from -82% to 321%, with a median of -36%. Using pCR as the reference standard and ROC curve methodology, %TOI TN AUC was 0.60 (95% CI, 0.39-0.81). In the cohort of 17 patients with baseline tumor oxygen saturation (%StO 2 ) greater than the 77% population median, %TOI TN AUC improved to 0.83 (95% CI, 0.63-1.00). We conclude that the combination of baseline functional properties and dynamic optical response shows promise for clinical outcome prediction. Cancer Res; 76(20); 5933-44. ©2016 AACR., Competing Interests: of Potential Conflicts of Interest: A. Cerussi and B.J. Tromberg report patents, which are owned by the University of California, that are related to the technology and analysis methods described in this study. The University of California has licensed diffuse optical spectroscopic imaging technology and analysis methods to LG, Inc. This research was completed without LG, Inc. participation, knowledge, or financial support and data were acquired and processed from patients by coauthors unaffiliated with this entity. The Institutional Review Board and Conflict of Interest Office of the University of California, Irvine, have reviewed both patent and corporate disclosures and did not find any concerns. No potential conflicts of interest were disclosed by the other authors., (©2016 American Association for Cancer Research.)

Background: The transient rise in blood lipids following a high-fat meal (HFM), known as postprandial lipemia, is linked to systemic inflammation and cardiovascular disease, but can be blunted by exercise. However, minimal research has investigated the effects of realistic exercise bouts on postprandial lipemia and inflammation in at-risk individuals. The purpose of this study was to assess the effects of moderate-intensity aerobic exercise lasting 30 or 60 min performed the evening before a HFM, on postprandial lipemia and inflammation in overweight, insufficiently active men., Methods: In this randomized-crossover study, twelve participants remained sedentary (CON), or performed a brisk walk on a treadmill at 60 % VO2peak for either 30 min (EX-30) or 60 min (EX-60), after which they consumed a small snack (270 kcal) to partially replace exercise energy expenditure. Following a 12-h overnight fast, participants consumed a standard HFM (1 g fat/kg; 1 g CHO/kg; 1117.8 ± 117.0 kcal). Blood draws were performed at baseline (pre-HFM) and 1, 2, 4, 6, and 8 h post-HFM to assess glucose, insulin, lipids, and systemic inflammation., Results: There were no significant differences (p > 0.05) in fasting triglycerides between EX-60 (118.7 ± 68.3 mg/dL), CON (134.8 ± 66.2 mg/dL) or EX-30 (135.5 ± 85.4 mg/dL). There were no differences in peak, time-to-peak, total or incremental area-under-the-curve between trials for triglyceride response (p > 0.05). There was no significant main effect of time (p > 0.05) in IL-1ra, IL-4, IL-5, IL-6, IL-10 or TNF-α from baseline to 8 h post-HFM in any trial., Conclusions: In summary, we found that in overweight, insufficiently active men, neither 30 nor 60 min of moderate-intensity exercise performed 12 h prior to a HFM attenuated postprandial lipemia or inflammation, which could potentially be explained by the partial caloric replacement of exercise energy expenditure.

Unlabelled: In a secondary analysis of American College of Radiology Imaging Network (ACRIN) 6668/RTOG 0235, high pretreatment metabolic tumor volume (MTV) on (18)F-FDG PET was found to be a poor prognostic factor for patients treated with chemoradiotherapy for locally advanced non-small cell lung cancer (NSCLC). Here we utilize the same dataset to explore whether heterogeneity metrics based on PET textural features can provide additional prognostic information., Methods: Patients with locally advanced NSCLC underwent (18)F-FDG PET prior to treatment. A gradient-based segmentation tool was used to contour each patient's primary tumor. MTV, maximum SUV, and 43 textural features were extracted for each tumor. To address overfitting and high collinearity among PET features, the least absolute shrinkage and selection operator (LASSO) method was applied to identify features that were independent predictors of overall survival (OS) after adjusting for MTV. Recursive binary partitioning in a conditional inference framework was utilized to identify optimal thresholds. Kaplan-Meier curves and log-rank testing were used to compare outcomes among patient groups., Results: Two hundred one patients met inclusion criteria. The LASSO procedure identified 1 textural feature (SumMean) as an independent predictor of OS. The optimal cutpoint for MTV was 93.3 cm(3), and the optimal SumMean cutpoint for tumors above 93.3 cm(3) was 0.018. This grouped patients into three categories: low tumor MTV (n = 155; median OS, 22.6 mo), high tumor MTV and high SumMean (n = 23; median OS, 20.0 mo), and high tumor MTV and low SumMean (n = 23; median OS, 6.2 mo; log-rank P < 0.001)., Conclusion: We have described an appropriate methodology to evaluate the prognostic value of textural PET features in the context of established prognostic factors. We have also identified a promising feature that may have prognostic value in locally advanced NSCLC patients with large tumors who are treated with chemoradiotherapy. Validation studies are warranted., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Study Objective: Three large, multicenter, randomized, clinical trials have shown that coronary computed tomography (CT) angiography allows efficient evaluation and safe discharge of patients with low- to intermediate-risk chest pain who present to the emergency department (ED). We report 1-year event rates and resource use from the American College of Radiology Imaging Network-Pennsylvania 4005 multicenter trial., Methods: Patients with low- to intermediate-risk chest pain and presenting to the ED were randomized in a 2:1 ratio to a coronary CT angiography care pathway or traditional care. Subjects were contacted by telephone at least 1 year after ED presentation. Medical record review was performed for all cardiac hospitalizations, procedures and diagnostic tests, and adverse cardiac events. Our main outcome was the composite of cardiac death and myocardial infarction within 1 year. The secondary outcome was resource use., Results: One thousand three hundred sixty-eight patients enrolled and 1,285 (94%) had direct participant or proxy contact at 1 year. All others had record review or death index search. From index presentation through 1 year, there was no difference between patients in the coronary CT angiography arm versus traditional care with respect to major adverse cardiac event (1.4% versus 1.1%; difference 0.3%; 95% CI -5.5% to 6.0%). From hospital discharge through 1 year, there was also no difference in ED revisits (36% versus 38%; difference -2.1%; 95% CI -7.9% to 3.7%), hospital admissions (16% versus 17%; difference -0.9%; 95% CI -6.7% to 4.9%), or subsequent cardiac testing (13% versus 13%; difference -0.4%; 95% CI -6.2% to 5.5%). One of 640 subjects with a negative coronary CT angiography result had a major adverse cardiac event within 1 year of presentation (0.16%; 95% CI 0.004% to 0.87%)., Conclusion: A coronary CT angiography-based strategy for evaluation of patients with low- to intermediate-risk chest pain who present to the ED does not result in increased resource use during 1 year. A negative coronary CT angiography result is associated with a less than 1% major adverse cardiac event rate during the first year after testing., (Copyright © 2015 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Purpose: The American College of Radiology Imaging Network (ACRIN) 6668/Radiation Therapy Oncology Group (RTOG) 0235 study demonstrated that standardized uptake values (SUV) on post-treatment [(18)F]fluorodeoxyglucose-positron emission tomography (FDG-PET) correlated with survival in locally advanced non-small cell lung cancer (NSCLC). This secondary analysis determined whether SUV of regional lymph nodes (RLNs) on post-treatment FDG-PET correlated with patient outcomes., Methods and Materials: Included for analysis were patients treated with concurrent chemoradiation therapy, using radiation doses ≥60 Gy, with identifiable FDG-avid RLNs (distinct from primary tumor) on pretreatment FDG-PET, and post-treatment FDG-PET data. ACRIN core laboratory SUV measurements were used. Event time was calculated from the date of post-treatment FDG-PET. Local-regional failure was defined as failure within the treated RT volume and reported by the treating institution. Statistical analyses included Wilcoxon signed rank test, Kaplan-Meier curves (log rank test), and Cox proportional hazards regression modeling., Results: Of 234 trial-eligible patients, 139 (59%) had uptake in both primary tumor and RLNs on pretreatment FDG-PET and had SUV data from post-treatment FDG-PET. Maximum SUV was greater for primary tumor than for RLNs before treatment (P<.001) but not different post-treatment (P=.320). Post-treatment SUV of RLNs was not associated with overall survival. However, elevated post-treatment SUV of RLNs, both the absolute value and the percentage of residual activity compared to the pretreatment SUV were associated with inferior local-regional control (P<.001)., Conclusions: High residual metabolic activity in RLNs on post-treatment FDG-PET is associated with worse local-regional control. Based on these data, future trials evaluating a radiation therapy boost should consider inclusion of both primary tumor and FDG-avid RLNs in the boost volume to maximize local-regional control., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Selecting resources to support didactic courses is a critical decision, and the advantages and disadvantages must be carefully considered. During clinical rotations, students not only need to possess strong background knowledge but also are expected to be proficient with the same evidence-based POC resources used by clinicians. Students place high value on “real world” learning and therefore may place more value on POC resources that they know practicing clinicians use as compared with medical textbooks. The condensed nature of PA education requires students to develop background knowledge and information literacy skills over a short period. One way to build that knowledge and those skills simultaneously is to use POC resources in lieu of traditional medical textbooks during didactic training. Electronic POC resources offer several advantages over traditional textbooks and should be considered as viable options in PA education.

Background: The study goal was to determine whether changes in relative cerebral blood volume (rCBV) derived from dynamic susceptibility contrast (DSC) MRI are predictive of overall survival (OS) in patients with recurrent glioblastoma multiforme (GBM) when measured 2, 8, and 16 weeks after treatment initiation., Methods: Patients with recurrent GBM (37/123) enrolled in ACRIN 6677/RTOG 0625, a multicenter, randomized, phase II trial of bevacizumab with irinotecan or temozolomide, consented to DSC-MRI plus conventional MRI, 21 with DSC-MRI at baseline and at least 1 postbaseline scan. Contrast-enhancing regions of interest were determined semi-automatically using pre- and postcontrast T1-weighted images. Mean tumor rCBV normalized to white matter (nRCBV) and standardized rCBV (sRCBV) were determined for these regions of interest. The OS rates for patients with positive versus negative changes from baseline in nRCBV and sRCBV were compared using Wilcoxon rank-sum and Kaplan-Meier survival estimates with log-rank tests., Results: Patients surviving at least 1 year (OS-1) had significantly larger decreases in nRCBV at week 2 (P = .0451) and sRCBV at week 16 (P = .014). Receiver operating characteristic analysis found the percent changes of nRCBV and sRCBV at week 2 and sRCBV at week 16, but not rCBV data at week 8, to be good prognostic markers for OS-1. Patients with positive change from baseline rCBV had significantly shorter OS than those with negative change at both week 2 and week 16 (P = .0015 and P = .0067 for nRCBV and P = .0251 and P = .0004 for sRCBV, respectively)., Conclusions: Early decreases in rCBV are predictive of improved survival in patients with recurrent GBM treated with bevacizumab., (© The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To evaluate three coronary artery calcification (CAC) scoring methods to assess risk of coronary heart disease (CHD) death and all-cause mortality in National Lung Screening Trial (NLST) participants across levels of CAC scores., Materials and Methods: The NLST was approved by the institutional review board at each participating institution, and informed consent was obtained from all participants. Image review was HIPAA compliant. Five cardiothoracic radiologists evaluated 1575 low-dose computed tomographic (CT) scans from three groups: 210 CHD deaths, 315 deaths not from CHD, and 1050 participants who were alive at conclusion of the trial. Radiologists used three scoring methods: overall visual assessment, segmented vessel-specific scoring, and Agatston scoring. Weighted Cox proportional hazards models were fit to evaluate the association between scoring methods and outcomes., Results: In multivariate analysis of time to CHD death, Agatston scores of 1-100, 101-1000, and greater than 1000 (reference category 0) were associated with hazard ratios of 1.27 (95% confidence interval: 0.69, 2.53), 3.57 (95% confidence interval: 2.14, 7.48), and 6.63 (95% confidence interval: 3.57, 14.97), respectively; hazard ratios for summed segmented vessel-specific scores of 1-5, 6-11, and 12-30 (reference category 0) were 1.72 (95% confidence interval: 1.05, 3.34), 5.11 (95% confidence interval: 2.92, 10.94), and 6.10 (95% confidence interval: 3.19, 14.05), respectively; and hazard ratios for overall visual assessment of mild, moderate, or heavy (reference category none) were 2.09 (95% confidence interval: 1.30, 4.16), 3.86 (95% confidence interval: 2.02, 8.20), and 6.95 (95% confidence interval: 3.73, 15.67), respectively., Conclusion: By using low-dose CT performed for lung cancer screening in older, heavy smokers, a simple visual assessment of CAC can be generated for risk assessment of CHD death and all-cause mortality, which is comparable to Agatston scoring and strongly associated with outcome., Competing Interests: of Conflicts of Interest: C.C. Financial activities related to the present article: disclosed no relevant relationships. Financial activities not related to the present article: author received money for consultancies from the National Cancer Institute and the American College of Radiology Imaging Network. Other relationships: disclosed no relevant relationships. F.D. disclosed no relevant relationships. G.W.G. disclosed no relevant relationships. J.G.R. disclosed no relevant relationships. S.G.B. disclosed no relevant relationships. B.S.S. disclosed no relevant relationships. S.D. disclosed no relevant relationships. S.S.D. disclosed no relevant relationships. R.F.M. disclosed no relevant relationships.

Objectives: The 2-hour accelerated diagnostic protocol (ADAPT) is a decision rule designed to identify emergency department (ED) patients with chest pain for early discharge. Previous studies in the Asia-Pacific region demonstrated high sensitivity (97.9% to 99.7%) for major adverse cardiac events (MACE) at 30 days. The objective of this study was to determine the validity of ADAPT for risk stratification in a cohort of U.S. ED patients with suspected acute coronary syndrome (ACS)., Methods: A secondary analysis of participants enrolled in the American College of Radiology Imaging Network (ACRIN) PA 4005 trial was conducted. This trial enrolled 1,369 patients at least 30 years old with symptoms suggestive of ACS. All data elements were collected prospectively at the time of enrollment. Each patient was classified as low risk or at risk by ADAPT. Early discharge rate and sensitivity for MACE, defined as cardiac death, myocardial infarction (MI), or coronary revascularization at 30 days, were calculated., Results: Of 1,140 patients with complete biomarker data, MACE occurred in 31 patients (2.7%). Among 551 of the 1,140 (48.3%, 95% confidence interval [CI] = 45.4% to 51.3%), ADAPT identified for early discharge; five of the 551 (0.9%, 95% CI = 0.3% to 2.1%) had MACE at 30 days. ADAPT was 83.9% (95% CI = 66.3% to 94.5%) sensitive, identifying 26 of 31 patients with MACE. Of the five patients identified for early discharge by ADAPT with MACE, there were no deaths, one patient with MI, and five with revascularizations., Conclusions: In this first North American application of the ADAPT strategy, sensitivity for MACE within 30 days was 83.9%. One missed adverse event was a MI, with the remainder representing coronary revascularizations. The effect of missing revascularization events needs further investigation., (© 2015 by the Society for Academic Emergency Medicine.)

Background: ACRIN 6668/RTOG 0235 evaluated the prognostic value of positron emission tomography with (18)F-fluorodeoxyglucose (FDG-PET) uptake before and after definitive, concurrent, platinum-based chemoradiotherapy for locally advanced non-small cell lung cancer (NSCLC). In this secondary analysis, we evaluate volumetric pretreatment PET measures as predictors of clinical outcomes., Methods: Patients with stage III NSCLC underwent FDG-PET prior to treatment. A commercially available gradient-based segmentation tool was used to contour all visible hypermetabolic lesions on each scan. For each patient, the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total glycolytic activity (TGA) for all contoured lesions were recorded. Cox proportional hazards regression models were used to evaluate clinical variables and PET metrics as predictors of overall survival (OS) and locoregional control (LRC). Time-dependent covariables were added to the models when necessary to address nonproportional hazards. All statistical tests were two-sided., Results: Complete data were available for 214 patients in the OS analysis and 189 subjects in the LRC analysis. In multivariable analysis incorporating clinical and imaging data available prior to treatment, MTV was an independent predictor of OS (HR = 1.04 per 10 cm(3) increase, 95% CI = 1.03 to 1.06, P < .001). High MTV was also associated with increased risk of locoregional failure at baseline (HR = 1.16 per 10 cm(3) increase, 95% CI = 1.08 to 1.23, P < .001) and at six months (HR = 1.05 per 10 cm(3) increase, 95% CI = 1.02 to 1.07, P < .001) but not at 12 months or later time points., Conclusion: Pretreatment MTV is a predictor of clinical outcomes for NSCLC patients treated with chemoradiotherapy. Quantitative PET measures may serve as stratification factors in clinical trials for this patient population and may help guide novel trial designs., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Low-dose computed tomography (LDCT) lung screening has been associated with a 20% reduction in lung cancer mortality. A major barrier to the adoption of lung screening is the potential negative psychological impact of a false-positive (FP) screen, occurring in 20% to 50% of those screened. The objective of this study was to assess the impact of abnormal findings on health-related quality of life (HRQoL) and anxiety in the American College of Radiology (ACRIN)/National Lung Screening Trial (NLST)., Methods: The NLST was a randomized screening trial comparing LDCT with chest X-ray screening (CXR). This study was part of the original protocol. A total of 2812 participants at 16 of 23 ACRIN sites who had baseline HRQoL assessments were asked to complete the Short Form-36 and the State Trait Anxiety Inventory (form Y-1) questionnaires to assess short-term (1 month) and long-term (6 months) effects of screening. FP were lung cancer-free at 1 year, and true-positives (TP) were not., Results: Of the total participants, 1024 (36.4%) participants were FP, 63 (2.2%) were TP, 344 (12.2%) had significant incidental findings (SIFs), and 1381 (49.1%) had negative screens. Participants had been randomized to LDCT (n = 1947) and CXR (n = 865). Short-term and long-term HRQoL and state anxiety did not differ across participants with FP, SIF, or negative screens. Short-term and long-term HRQoL were lower and anxiety was higher for TP participants compared to participants with FP, SIF, and negative screens., Conclusions: In a large multicenter lung screening trial, participants receiving a false-positive or SIF screen result experienced no significant difference in HRQoL or state anxiety at 1 or at 6 months after screening relative to those receiving a negative result., (© 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.)

Purpose: In this prospective National Cancer Institute-funded American College of Radiology Imaging Network/Radiation Therapy Oncology Group cooperative group trial, we hypothesized that standardized uptake value (SUV) on post-treatment [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) correlates with survival in stage III non-small-cell lung cancer (NSCLC)., Patients and Methods: Patients received conventional concurrent platinum-based chemoradiotherapy without surgery; postradiotherapy consolidation chemotherapy was allowed. Post-treatment FDG-PET was performed at approximately 14 weeks after radiotherapy. SUVs were analyzed both as peak SUV (SUVpeak) and maximum SUV (SUVmax; both institutional and central review readings), with institutional SUVpeak as the primary end point. Relationships between the continuous and categorical (cutoff) SUVs and survival were analyzed using Cox proportional hazards multivariate models., Results: Of 250 enrolled patients (226 were evaluable for pretreatment SUV), 173 patients were evaluable for post-treatment SUV analyses. The 2-year survival rate for the entire population was 42.5%. Pretreatment SUVpeak and SUVmax (mean, 10.3 and 13.1, respectively) were not associated with survival. Mean post-treatment SUVpeak and SUVmax were 3.2 and 4.0, respectively. Post-treatment SUVpeak was associated with survival in a continuous variable model (hazard ratio, 1.087; 95% CI, 1.014 to 1.166; P = .020). When analyzed as a prespecified binary value (≤ v > 3.5), there was no association with survival. However, in exploratory analyses, significant results for survival were found using an SUVpeak cutoff of 5.0 (P = .041) or 7.0 (P < .001). All results were similar when SUVmax was used in univariate and multivariate models in place of SUVpeak., Conclusion: Higher post-treatment tumor SUV (SUVpeak or SUVmax) is associated with worse survival in stage III NSCLC, although a clear cutoff value for routine clinical use as a prognostic factor is uncertain at this time.

Background: The prognosis for patients with recurrent glioblastoma remains poor. The purpose of this study was to assess the potential role of MR spectroscopy as an early indicator of response to anti-angiogenic therapy., Methods: Thirteen patients with recurrent glioblastoma were enrolled in RTOG 0625/ACRIN 6677, a prospective multicenter trial in which bevacizumab was used in combination with either temozolomide or irinotecan. Patients were scanned prior to treatment and at specific timepoints during the treatment regimen. Postcontrast T1-weighted MRI was used to assess 6-month progression-free survival. Spectra from the enhancing tumor and peritumoral regions were defined on the postcontrast T1-weighted images. Changes in the concentration ratios of n-acetylaspartate/creatine (NAA/Cr), choline-containing compounds (Cho)/Cr, and NAA/Cho were quantified in comparison with pretreatment values., Results: NAA/Cho levels increased and Cho/Cr levels decreased within enhancing tumor at 2 weeks relative to pretreatment levels (P = .048 and P = .016, respectively), suggesting a possible antitumor effect of bevacizumab with cytotoxic chemotherapy. Nine of the 13 patients were alive and progression free at 6 months. Analysis of receiver operating characteristic curves for NAA/Cho changes in tumor at 8 weeks revealed higher levels in patients progression free at 6 months (area under the curve = 0.85), suggesting that NAA/Cho is associated with treatment response. Similar results were observed for receiver operating characteristic curve analyses against 1-year survival. In addition, decreased Cho/Cr and increased NAA/Cr and NAA/Cho in tumor periphery at 16 weeks posttreatment were associated with both 6-month progression-free survival and 1-year survival., Conclusion: Changes in NAA and Cho by MR spectroscopy may potentially be useful as imaging biomarkers in assessing response to anti-angiogenic treatment.

Background: RTOG 0625/ACRIN 6677 is a multicenter, randomized, phase II trial of bevacizumab with irinotecan or temozolomide in recurrent glioblastoma (GBM). This study investigated whether early posttreatment progression on FLAIR or postcontrast MRI assessed by central reading predicts overall survival (OS)., Methods: Of 123 enrolled patients, 107 had baseline and at least 1 posttreatment MRI. Two central neuroradiologists serially measured bidimensional (2D) and volumetric (3D) enhancement on postcontrast T1-weighted images and volume of FLAIR hyperintensity. Progression status on all posttreatment MRIs was determined using Macdonald and RANO imaging threshold criteria, with a third neuroradiologist adjudicating discrepancies of both progression occurrence and timing. For each MRI pulse sequence, Kaplan-Meier survival estimates and log-rank test were used to compare OS between cases with or without radiologic progression., Results: Radiologic progression occurred after 2 chemotherapy cycles (8 weeks) in 9 of 97 (9%), 9 of 73 (12%), and 11 of 98 (11%) 2D-T1, 3D-T1, and FLAIR cases, respectively, and 34 of 80 (43%), 21 of 58 (36%), and 37 of 79 (47%) corresponding cases after 4 cycles (16 weeks). Median OS among patients progressing at 8 or 16 weeks was significantly less than that among nonprogressors, as determined on 2D-T1 (114 vs 278 days and 214 vs 426 days, respectively; P < .0001 for both) and 3D-T1 (117 vs 306 days [P < .0001] and 223 vs 448 days [P = .0003], respectively) but not on FLAIR (201 vs 276 days [P = .38] and 303 vs 321 days [P = .13], respectively)., Conclusion: Early progression on 2D-T1 and 3D-T1, but not FLAIR MRI, after 8 and 16 weeks of anti-vascular endothelial growth factor therapy has highly significant prognostic value for OS in recurrent GBM.

Purpose: To compare whole-body magnetic resonance (MR) imaging with conventional imaging for detection of distant metastases in pediatric patients with common malignant tumors., Materials and Methods: This institutional review board-approved, HIPAA-compliant, multicenter prospective cohort study included 188 patients (109 male, 79 female; mean age, 10.2 years; range, < 1 to 21 years) with newly diagnosed lymphoma, neuroblastoma, or soft-tissue sarcoma. Informed consent was obtained and all patients underwent noncontrast material-enhanced whole-body MR imaging and standard-practice conventional imaging. All images were reviewed centrally by 10 pairs of readers. An independent panel verified the presence or absence of distant metastases. Detection of metastasis with whole-body MR and conventional imaging was quantified by using the area under the receiver operating characteristic curve (AUC). The effects of tumor subtype, patient age, and distant skeletal and pulmonary disease on diagnostic accuracy were also analyzed., Results: Of the 134 eligible patients, 66 (33 positive and 33 negative for metastasis) were selected for image review and analysis. Whole-body MR imaging did not meet the noninferiority criterion for accuracy when compared with conventional imaging for detection of metastasis (difference between average AUCs was -0.03 [95% confidence interval: -0.10, 0.04]); however, the average AUC for solid tumors was significantly higher than that for lymphomas (P = .006). More skeletal metastases were detected by using whole-body MR imaging than by using conventional imaging (P = .03), but fewer lung metastases were detected (P < .001). Patient age did not affect accuracy., Conclusion: The noninferior accuracy for diagnosis of distant metastasis in patients with common pediatric tumors was not established for the use of whole-body MR imaging compared with conventional methods. However, improved accuracy was seen with whole-body MR imaging in patients with nonlymphomatous tumors.

Objective. The objective was to compare the postprandial glycemic and insulinemic responses to nutrition bars containing either cross-linked RS type 4 (RS4(XL)) or standard wheat starch in normoglycemic adults (n = 13; age = 27 +/- 5 years; BMI = 25 +/- 3 kg/m(2)). Methods. Volunteers completed three trials during which they consumed a glucose beverage (GLU), a puffed wheat control bar (PWB), and a bar containing cross-linked RS4 (RS4(XL)) matched for available carbohydrate content. Serial blood samples were collected over two hours and glucose and insulin concentrations were determined and the incremental area under the curve (iAUC) was calculated. Results. The RS4(XL) peak glucose and insulin concentrations were lower than the GLU and PWB (P < .05). The iAUC for glucose and insulin were lower following ingestion of RS4 compared with the GLU and PWB trials. Conclusions. These data illustrate, for the first time, that directly substituting standard starch with RS4(XL), while matched for available carbohydrates, attenuated postprandial glucose and insulin levels in humans. It remains to be determined whether this response was due to the dietary fiber and/or resistant starch aspects of the RS4(XL) bar.

Alterations of skeletal muscle redox state via antioxidant supplementation have the potential to impact contractile function and vascular smooth muscle tone. The effects of antioxidants on the regulation of muscle O(2) delivery-O(2) utilization (Q(O(2)m/V(O(2)m)) matching (which sets the microvascular partial pressure of O(2); P(O(2)mv)) in young healthy muscle are not known. Therefore, the purpose of this study was to test the effects of acute antioxidant supplementation on rat spinotrapezius muscle force production, blood flow, V(O(2)m) and P(O(2)mv) (phosphorescence quenching). Anaesthetized male Fischer 344 x Brown Norway rats (6-8 months old) had their right spinotrapezius muscles either exposed for measurement of blood flow and (n = 13) or exteriorized for measurement of muscle force production (n = 6). Electrically stimulated 1 Hz twitch contractions (approximately 7-9 V) were elicited for 180 s, and measurements were made before and after acute intra-arterial antioxidant supplementation (76 mg kg(-1) ascorbic acid, 52 mg kg(-1) tempol) dissolved in saline and infused over 30 min. The principal effects of antioxidants were a approximately 25% decrease (P < 0.05) in contracting spinotrapezius muscle force production concurrent with reductions in muscle blood flow and V(O(2)m) at rest and during contractions (P < 0.05 for both). Antioxidant supplementation reduced the resting baseline P(O(2)mv) (before, 29.9 +/- 1.2 mmHg; after, 25.6 +/- 1.3 mmHg; P < 0.05), and this magnitude of depression was sustained throughout the rest-to-exercise transition (steady-state value before, 16.4 +/- 0.7 mmHg; after, 13.6 +/- 0.9 mmHg; P < 0.05). In addition, the time constant of the P(O(2)mv) decrease was reduced after antioxidant supplementation (before, 23.4 +/- 4.3 s; after, 15.6 +/- 2.7 s; P < 0.05). These results demonstrate that antioxidant supplementation significantly impacts the control of (Q(O(2)m/V(O(2)m)) in young rats at rest and during contractions.

Aged rats exhibit a decreased muscle microvascular O(2) partial pressure (Pmv(O(2))) at rest and during contractions compared with young rats. Age-related reductions in nitric oxide bioavailability due, in part, to elevated reactive O(2) species, constrain muscle blood flow (Qm). Antioxidants may restore nitric oxide bioavailability, Qm, and ameliorate the reduced Pmv(O(2)). We tested the hypothesis that antioxidants would elevate Qm and, therefore, Pmv(O(2)) in aged rats. Spinotrapezius muscle Pmv(O(2)) and Qm were measured, and oxygen consumption (Vm(O(2))) was estimated in anesthetized male Fisher 344 x Brown Norway hybrid rats at rest and during 1-Hz contractions, before and after antioxidant intravenous infusion (76 mg/kg vitamin C and 52 mg/kg tempol). Before infusion, contractions evoked a biphasic Pmv(O(2)) that fell from 30.6 +/- 0.9 Torr to a nadir of 16.8 +/- 1.2 Torr with an "undershoot" of 2.8 +/- 0.7 Torr below the subsequent steady-state (19.7 +/- 1.2 Torr). The principal effect of antioxidants was to elevate baseline Pmv(O(2)) from 30.6 +/- 0.9 to 35.7 +/- 0.8 Torr (P < 0.05) and reduce or abolish the undershoot (P < 0.05). Antioxidants reduced Qm and Vm(O(2)) during contractions (P < 0.05), while decreasing force production 16.5% (P < 0.05) and elevating the force production-to-Vm(O(2)) ratio (0.92 +/- 0.03 to 1.06 +/- 0.6, P < 0.05). Thus antioxidants increased Pmv(O(2)) by altering the balance between muscle O(2) delivery and Vm(O(2)) at rest and during contractions. It is likely that this effect arose from antioxidants reducing myocyte redox below the level optimal for contractile performance and directly (decreased tension) or indirectly (altered balance of vasoactive mediators) influencing O(2) delivery and Vm(O(2)).

Objective: To uncover the meaning of living with polycystic ovary syndrome., Design: Phenomenology., Setting: A women's health care practice in northeast United States., Participants: A purposive sample consisting of 12 women, ages 21 to 48 years, who had been previously diagnosed with polycystic ovary syndrome., Data Collection: Semistructured interviews., Results: Analysis of the participants' responses revealed the following themes: (a) identifying differences, (b) wanting to be normal, (c) searching for answers, (d) gaining control, (e) attempting to achieve femininity, (f) letting go of guilt, and (g) dealing with it., Conclusions: Polycystic ovary syndrome is a syndrome that impacts women both physically and psychosocially. Nurses can play a key role in assisting women afflicted with this hormonal disturbance through education and support.

The anterior cruciate ligament (ACL) of the knee fails to heal after primary repair. Here we hypothesize that a beneficial biologic repair response can be induced by placing a collagen-platelet rich plasma (collagen-PRP) material into a central ACL defect. A collagen-PRP scaffold was used to treat a central ACL defect in vivo. In the first experiment, the histologic response in treated and untreated defects was evaluated at 3 (n = 5) and 6 weeks (n = 5). In the second experiment, biomechanical testing of the treated ligaments (n = 8) was performed at 6 weeks and compared with the results of biomechanical testing of untreated defects at the same time-point (n = 6). The percentage filling of the defects in the treated ACLs was significantly higher at both the 3- and 6-week time-points when compared with the untreated contralateral control defects (50 +/- 21% vs. 2 +/- 2% at 3 weeks, and 43 +/- 11% vs. 23 +/- 11 at 6 weeks; all values mean +/- SEM. Biomechanically, the treated ACL defects had a 40% increase in strength at 6 weeks, which was significantly higher than the 14% increase in strength previously reported for untreated defects (p < 0.02). Placement of a collagen-PRP bridging scaffold in a central ACL defect can stimulate healing of the ACL histologically and biomechanically., (Copyright 2006 Orthopaedic Research Society)