Sulindac Improves Stiffness and Quality of Life in Women Taking Aromatase Inhibitors for Breast Cancer.

PURPOSE: To examine benefit of sulindac for relief of musculoskeletal symptoms (MSS) in patients stable on aromatase inhibitors (AIs). METHODS: Sulindac was evaluated at 150 mg twice daily for effects on MSS at 3, 6, 9, and 12 months in 50 postmenopausal women stable on AI therapy for a median of 12.5 months for hormone receptor-positive breast cancer. A separate, non-randomized group of 50 similar patients was observed for change in MSS over 12 months. MSS severity was assessed using the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index and Brief Pain Inventory Short Form (BPI-SF). The Functional Assessment of Cancer Therapy-General form (FACT-G) measured quality of life (QOL). Change in MSS and QOL across time was assessed in each group using linear mixed effects models. RESULTS: Stiffness, not pain, was the main complaint at baseline. At 12 months, sulindac patients reported decreases (improvements) in mean (95% CI) Total WOMAC score [- 5.85 (- 9.73, - 1.96)] and WOMAC pain [- 5.40 (- 10.64, - 0 .18)], Stiffness [- 9.53 (- 14.98, - 4.08)] and Physical Function [- 5.61 (- 9.62, - 1.60)] subscales, but not BPI-SF worst pain. Among sulindac patients with higher baseline MSS severity, 35% experienced ≥ 50% improvement in Total WOMAC and Total FACT-G scores [6.18 (2.08, 10.27); P = 0.003]. For the observation group, MSS and QOL did not improve over 12 months, even among those with higher baseline MSS severity. CONCLUSIONS: Sulindac may relieve MSS in AI patients, especially physical function and stiffness. Randomized controlled trials should further evaluate NSAIDs on AI-MSS and AI adherence. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: NCT01761877, December, 2012.

Integration of metabolomics and transcriptomics reveals convergent pathways driving radiation-induced salivary gland dysfunction.

Radiation therapy for head and neck cancer causes damage to the surrounding salivary glands, resulting in salivary gland hypofunction and xerostomia. Current treatments do not provide lasting restoration of salivary gland function following radiation; therefore, a new mechanistic understanding of the radiation-induced damage response is necessary for identifying therapeutic targets. The purpose of the present study was to investigate the metabolic phenotype of radiation-induced damage in parotid salivary glands by integrating transcriptomic and metabolomic data. Integrated data were then analyzed to identify significant gene-metabolite interactions. Mice received a single 5 Gy dose of targeted head and neck radiation. Parotid tissue samples were collected 5 days following treatment for RNA sequencing and metabolomics analysis. Altered metabolites and transcripts significantly converged on a specific region in the metabolic reaction network. Both integrative pathway enrichment using rank-based statistics and network analysis highlighted significantly coordinated changes in glutathione metabolism, energy metabolism (TCA cycle and thermogenesis), peroxisomal lipid metabolism, and bile acid production with radiation. Integrated changes observed in energy metabolism suggest that radiation induces a mitochondrial dysfunction phenotype. These findings validated previous pathways involved in the radiation-damage response, such as altered energy metabolism, and identified robust signatures in salivary glands, such as reduced glutathione metabolism, that may be driving salivary gland dysfunction.

A randomized controlled trial of metformin in women with components of metabolic syndrome: intervention feasibility and effects on adiposity and breast density.

PURPOSE: Obesity is a known risk factor for post-menopausal breast cancer and may increase risk for triple negative breast cancer in premenopausal women. Intervention strategies are clearly needed to reduce obesity-associated breast cancer risk. METHODS: We conducted a Phase II double-blind, randomized, placebo-controlled trial of metformin in overweight/obese premenopausal women with components of metabolic syndrome to assess the potential of metformin for primary breast cancer prevention. Eligible participants were randomized to receive metformin (850 mg BID, n = 76) or placebo (n = 75) for 12 months. Outcomes included breast density, assessed by fat/water MRI with change in percent breast density as the primary endpoint, anthropometric measures, and intervention feasibility. RESULTS: Seventy-six percent in the metformin arm and 83% in the placebo arm (p = 0.182) completed the 12-month intervention. Adherence to study agent was high with more than 80% of participants taking ≥ 80% assigned pills. The most common adverse events reported in the metformin arm were gastrointestinal in nature and subsided over time. Compared to placebo, metformin intervention led to a significant reduction in waist circumference (p < 0.001) and waist-to-hip ratio (p = 0.019). Compared to placebo, metformin did not change percent breast density and dense breast volume but led to a numerical but not significant decrease in non-dense breast volume (p = 0.070). CONCLUSION: We conclude that metformin intervention resulted in favorable changes in anthropometric measures of adiposity and a borderline decrease in non-dense breast volume in women with metabolic dysregulation. More research is needed to understand the impact of metformin on breast cancer risk reduction. TRIAL REGISTRATION: ClinicalTrials.gov NCT02028221. Registered January 7, 2014, https://clinicaltrials.gov/ct2/show/NCT02028221.

Patient Questions Surrounding Mask Use for Prevention of COVID-19 and Physician Answers from an Evidence-Based Perspective: a Narrative Review.

Recent mandates to wear masks in public places across the USA combined with conflicting messaging from the media and government agencies have generated a lot of patient questions surrounding the appropriate use and efficacy of cloth masks. Here, we have organized the evidence in the context of real patient questions and have provided example answers from a physician's perspective. The purpose of this review is to offer healthcare providers with examples of how to respond to patient questions about masks in a way that encourages responsible decision-making. We conclude, based on the evidence showing a benefit for cloth masks and the recent reports supporting a role for aerosols in the transmission of SARS-CoV-2, that cloth masks will be effective when used correctly. We further assert that stronger public messaging surrounding cloth masks in the community setting is needed, and should specify that 2-3 layer, fitted face masks be worn at all times in public as another layer of protection in addition to social distancing, not just when social distancing cannot be maintained.

Evaluation of a Workflow to Define Low Specific Absorption Rate MRI Protocols for Patients With Active Implantable Medical Devices.

BACKGROUND: MRI exams for patients with MR-conditional active implantable medical devices (AIMDs) are contraindicated unless specific conditions are met. This limits the maximum specific absorption rate (SAR, W/kg). Currently, there is no general framework to guide meeting a lower SAR limit. PURPOSE: To design and evaluate a workflow for modifying MRI protocols to whole-body SAR (WB-SAR ≤0.1 W/kg) and local-head SAR (LH-SAR ≤0.3 W/kg) limits while mitigating the impact on image quality and exam time. STUDY TYPE: Prospective. POPULATION: Twenty healthy volunteers on head (n = 5), C-spine (n = 5), T-spine (n = 5), and L-spine (n = 5) with IRB consent. ASSESSMENT: Vendor-provided head, C-spine, T-spine, and L-spine protocols (SARRT ) were modified to meet both low SAR targets (SARLOW ) using the proposed workflow. in vitro SNR and CNR were evaluated with a T1 -T2 phantom. in vivo image quality and clinical acceptability were scored using a 5-point Likert scale for two blinded readers. FIELD STRENGTH/SEQUENCES: 1.5T/spin-echoes, gradient-echoes. STATISTICAL ANALYSIS: In vitro SNR and CNR values were evaluated with a repeated measures general linear model. in vivo image quality and clinical acceptability were evaluated using a generalized estimating equation analysis (GEE). The two reader's level of agreement was analyzed using Cohen's kappa statistical analysis. RESULTS: Using the workflow, SAR limits were met. LH-SAR: 0.12 ± 0.02 W/kg, median (SD) values for LH-SAR were 0.12 (0.02) W/kg and WB-SAR: 0.09 (0.01) W/kg. Examination time did not increase ≤2x the initial time. SARRT SNR values were higher and significantly different than SARLOW (P < 0.05). However, no significant difference was observed between the CNR values (value = 0.21). Median (IQR) CNR values were 14.2 (25.0) vs. 15.1 (9.2) for head, 12.1 (16.9) vs. 25.3 (14.2) for C-spine, 81.6 (70.1) vs. 71.0 (26.6) for T-spine, and 51.4 (52.6) vs. 37.7 (27.3) for L-spine. Image quality scores were not significantly different between SARRT and SARLOW (median [SD] scores were 4.0 [0.01] vs. 4.3 [0.2], P > 0.05). DATA CONCLUSION: The proposed workflow provides guidance for modifying routine MRI exams to achieve low SAR limits. This can benefit patients referred for an MRI exam with low SAR MR-conditional AIMDs. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2020;52:91-102.

Feasibility and acceptability of a beverage intervention for Hispanic adults: results from a pilot randomized controlled trial.

OBJECTIVE: To assess the feasibility and acceptability of a beverage intervention in Hispanic adults. DESIGN: Eligible individuals identified as Hispanic, were 18-64 years old and had BMI 30·0-50·0 kg/m2. Participants were randomized 2:2:1 to one of three beverages: Mediterranean lemonade (ML), green tea (GT) or flavoured water control (FW). After a 2-week washout period, participants were asked to consume 32 oz (946 ml) of study beverage daily for 6 weeks and avoid other sources of tea, citrus, juice and sweetened beverages; water was permissible. Fasting blood samples were collected at baseline and 8 weeks to assess primary and secondary efficacy outcomes. SETTING: Tucson, AZ, USA.ParticipantsFifty-two participants were recruited over 6 months; fifty were randomized (twenty-one ML, nineteen GT, ten FW). Study population mean (sd) age 44·6 (sd 10·2) years, BMI 35·9 (4·6) kg/m2; 78 % female. RESULTS: Forty-four (88 %) completed the 8-week assessment. Self-reported adherence was high. No significant change (95 % CI) in total cholesterol (mg/dl) from baseline was shown -1·7 (-14·2, 10·9), -3·9 (-17·2, 9·4) and -13·2 (-30·2, 3·8) for ML, GT and FW, respectively. Mean change in HDL-cholesterol (mg/dl) -2·3 (-5·3, 0·7; ML), -1·0 (-4·2, 2·2; GT), -3·9 (-8·0, 0·2; FW) and LDL-cholesterol (mg/dl) 0·2 (-11·3, 11·8; ML), 0·5 (-11·4, 12·4; GT), -9·8 (-25·0, 5·4; FW) were also non-significant. Fasting glucose (mg/dl) increased significantly by 5·2 (2·6, 7·9; ML) and 3·3 (0·58, 6·4; GT). No significant change in HbA1c was demonstrated. Due to the small sample size, potential confounders and effect modifiers were not investigated. CONCLUSIONS: Recruitment and retention figures indicate that a larger-scale trial is feasible; however, favourable changes in cardiometabolic biomarkers were not demonstrated.

Feasibility and acceptability of a beverage intervention for Hispanic adults: a protocol for a pilot randomized controlled trial.

BACKGROUND: In the U.S., Hispanics have among the highest rates of overweight and obesity when compared to other racial/ethnic groups placing them at a greater risk for obesity-related disease. Identifying intervention strategies to reduce caloric intake and/or improve cardiometabolic health in Hispanics is critical to reducing morbidity and mortality among this large and growing population. Evidence exists to support diet-specific behavioral interventions, including beverage modifications, in reducing obesity-related health risks. However, the acceptability and feasibility of a beverage intervention in obese Hispanic adults has not been robustly evaluated. METHODS: The objective of this pilot study is to assess the feasibility and acceptability of a randomized, controlled beverage intervention in 50 obese Hispanic adults ages 18-64 over 8-weeks. Eligible participants were obese (30-50.0 kg/m2), between the ages 18-64, self-identified as Hispanic, and were able to speak, read, and write in either English and/or Spanish. Study recruitment was completed August 2017. Upon the completion of baseline assessments, participants will be randomized to either Mediterranean lemonade, Green Tea, or flavored water control. After completing a 2-week washout period, participants will be asked to consume 32 oz. per day of study beverage for 6-weeks while avoiding all other sources of tea, lemonade, citrus, juice, and other sweetened beverages; water is permissible. Primary outcomes will be recruitment, retention, and acceptability of the intervention strategies. Our study will also evaluate participant-reported tolerance and as an exploratory aim, assess safety/toxicity-related to renal and/or liver function. Fasting blood samples will be collected at baseline and 8-weeks to assess the primary efficacy outcomes: total cholesterol, high-density lipoprotein (HDL), and low-density lipoprotein (LDL). Secondary outcomes include fasting glucose, hemoglobin A1c (HbA1c), and high-sensitivity C-reactive protein (hs-CRP). DISCUSSION: This pilot study will provide important feasibility, safety, and early efficacy data necessary to design a larger, adequately-powered randomized controlled trial. TRIAL REGISTRATION: NCT02911753 ( ClinicalTrials.gov ). Registered September 19, 2016. Last updated November 1, 2017.

Phase II study of metformin for reduction of obesity-associated breast cancer risk: a randomized controlled trial protocol.

BACKGROUND: Two-thirds of U.S. adult women are overweight or obese. High body mass index (BMI) and adult weight gain are risk factors for a number of chronic diseases, including postmenopausal breast cancer. The higher postmenopausal breast cancer risk in women with elevated BMI is likely to be attributable to related metabolic disturbances including altered circulating sex steroid hormones and adipokines, elevated pro-inflammatory cytokines, and insulin resistance. Metformin is a widely used antidiabetic drug that has demonstrated favorable effects on metabolic disturbances and as such may lead to lower breast cancer risk in obese women. Further, the anti-proliferative effects of metformin suggest it may decrease breast density, an accepted biomarker of breast cancer risk. METHODS/DESIGN: This is a Phase II randomized, double-blind, placebo-controlled trial of metformin in overweight/obese premenopausal women who have elements of metabolic syndrome. Eligible participants will be randomized to receive metformin 850 mg BID (n = 75) or placebo (n = 75) for 12 months. The primary endpoint is change in breast density, based on magnetic resonance imaging (MRI) acquired fat-water features. Secondary outcomes include changes in serum insulin levels, serum insulin-like growth factor (IGF)-1 to insulin-like growth factor binding protein (IGFBP)-3 ratio, serum IGF-2 levels, serum testosterone levels, serum leptin to adiponectin ratio, body weight, and waist circumference. Exploratory outcomes include changes in metabolomic profiles in plasma and nipple aspirate fluid. Changes in tissue architecture as well as cellular and molecular targets in breast tissue collected in a subgroup of participants will also be explored. DISCUSSION: The study will evaluate whether metformin can result in favorable changes in breast density, select proteins and hormones, products of body metabolism, and body weight and composition. The study should help determine the potential breast cancer preventive activity of metformin in a growing population at risk for multiple diseases. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02028221 . Registered on January 2, 2014. Grant #: 1R01CA172444-01A1 awarded on Sept 11, 2013.

Phase-sensitive deep reconstruction method for rapid multiparametric MR fingerprinting and quantitative susceptibility mapping in the brain.

INTRODUCTION: This study explores the potential of Magnetic Resonance Fingerprinting (MRF) with a novel Phase-Sensitivity Deep Reconstruction Network (PS-DRONE) for simultaneous quantification of T1, T2, Proton Density, B1+, phase and quantitative susceptibility mapping (QSM). METHODS: Data were acquired at 3 T in vitro and in vivo using an optimized EPI-based MRF sequence. Phantom experiments were conducted using a standardized phantom for T1 and T2 maps and a custom-made agar-based gadolinium phantom for B1 and QSM maps. In vivo experiments included five healthy volunteers and one patient diagnosed with brain metastasis. PSDRONE maps were compared to reference maps obtained through standard imaging sequences. RESULTS: Total scan time was 2 min for 32 slices and a resolution of [1 mm, 1 mm, 4.5 mm]. The reconstruction of T1, T2, Proton Density, B1+ and phase maps were reconstructed within 1 s. In the phantoms, PS-DRONE analysis presented accurate and strongly correlated T1 and T2 maps (r = 0.99) compared to the reference maps. B1 maps from PS-DRONE showed slightly higher values, though still correlated (r = 0.6) with the reference. QSM values showed a small bias but were strongly correlated (r = 0.99) with reference data. In the in vivo analysis, PS-DRONE-derived T1 and T2 values for gray and white matter matched reference values in healthy volunteers. PS-DRONE B1 and QSM maps showed strong correlations with reference values. CONCLUSION: The PS-DRONE network enables concurrent acquisition of T1, T2, PD, B1+, phase and QSM maps, within 2 min of acquisition time and 1 s of reconstruction time.

Hospital Days Reduced for Moderate and Severe COVID-19 Patients Through a Home Monitoring Program With Oxygen.

While the COVID-19 pandemic continues to strain the healthcare system, it has also expanded telemedicine. There is a subset of hospitalized moderate to severe COVID-19 patients requiring oxygen but no other intervention. This is a retrospective study of patients ≥18 years with moderate to severe COVID-19 that participated in a home monitoring program with supplemental oxygen (HMP-O2) (N = 25). For study outcomes, HMP-O2 participants were compared to patients meeting the same inclusion criteria but did not participate in the program (N = 60). On average, the HMP-O2 patients spent 5.8 days (±5.5 days) in the hospital compared to 8.12 days (±5.5 days) for non-program patients. This resulted in 19% cost-savings for HMP-O2 patients. Lessons learned from this program can be applied to future HMPs for either COVID-19 or other conditions that would benefit from telecare.

Differences in Metabolomic Profiles by Birthplace in Mexican-Origin Hispanic Men Who Participated in a Weight Loss Lifestyle Intervention.

Birthplace, as a proxy for environmental exposures (e.g., diet), may influence metabolomic profiles and influence risk of cancer. This secondary analysis investigated metabolomic profile differences between foreign and U.S.-born Mexican-origin (MO) Hispanic men to shed light on potential mechanisms through which foreign- and U.S.-born individuals experience differences in cancer risk and risk factors. Plasma samples from MO Hispanic men (N = 42) who participated in a previous lifestyle intervention were collected pre-and post-intervention. Metabolomic profiles were characterized from samples using ultra performance liquid chromatography-quadrupole time of flight mass spectrometry (UPLC-QTOF). Models were visualized using supervised orthogonal projections to latent structures-discriminant analysis (OPLS-DA). Progenesis QI was used for peak integration and metabolite identification. Plasma metabolomic profiles differed between foreign- and U.S.-born pre-intervention (R2 = .65) and post-intervention (R2 = .62). Metabolomic profiles differed pre- versus post-intervention (R2 = .35 and R2 = .65) for the foreign- and U.S.-born group, respectively. Both endogenous metabolites and dietary components characterized differences between foreign- and U.S.-born participants pre- and post-intervention. Plasma metabolomic profiles from MO Hispanic men differed by birthplace. These results advance our understanding of relevant exposures that may affect cancer risk among MO Hispanic men born abroad or in the United States.

Metabolomics analysis of pathways underlying radiation-induced salivary gland dysfunction stages.

Salivary gland hypofunction is an adverse side effect associated with radiotherapy for head and neck cancer patients. This study delineated metabolic changes at acute, intermediate, and chronic radiation damage response stages in mouse salivary glands following a single 5 Gy dose. Ultra-high performance liquid chromatography-mass spectrometry was performed on parotid salivary gland tissue collected at 3, 14, and 30 days following radiation (IR). Pathway enrichment analysis, network analysis based on metabolite structural similarity, and network analysis based on metabolite abundance correlations were used to incorporate both metabolite levels and structural annotation. The greatest number of enriched pathways are observed at 3 days and the lowest at 30 days following radiation. Amino acid metabolism pathways, glutathione metabolism, and central carbon metabolism in cancer are enriched at all radiation time points across different analytical methods. This study suggests that glutathione and central carbon metabolism in cancer may be important pathways in the unresolved effect of radiation treatment.

Oxylipins as Biomarkers for Aromatase Inhibitor-Induced Arthralgia (AIA) in Breast Cancer Patients.

Aromatase inhibitor-induced arthralgia (AIA) presents a major problem for patients with breast cancer but is poorly understood. This prospective study explored the inflammatory metabolomic changes in the development of AIA. This single-arm, prospective clinical trial enrolled 28 postmenopausal women with early-stage (0-3) ER+ breast cancer starting adjuvant anastrozole. Patients completed the Breast Cancer Prevention Trial (BCPT) Symptom Checklist and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) at 0, 3, and 6 months. The plasma levels of four polyunsaturated fatty acids (PUFAs) and 48 oxylipins were quantified at each timepoint. The subscores for WOMAC-pain and stiffness as well as BCPT-total, hot flash, and musculoskeletal pain significantly increased from baseline to 6 months (all p < 0.05). PUFA and oxylipin levels were stable over time. The baseline levels of 8-HETE were positively associated with worsening BCPT-total, BCPT-hot flash, BCPT-musculoskeletal pain, WOMAC-pain, and WOMAC- stiffness at 6 months (all p < 0.05). Both 9-HOTrE and 13(S)-HOTrE were related to worsening hot flash, and 5-HETE was related to worsening stiffness (all p < 0.05). This is the first study to prospectively characterize oxylipin and PUFA levels in patients with breast cancer starting adjuvant anastrozole. The oxylipin 8-HETE should be investigated further as a potential biomarker for AIA.

The Importance of Drug Concentration at the Site of Action: Celecoxib and Colon Polyp Prevention as a Case Study.

Celecoxib is among the more potent and better clinically studied, nonsteroidal anti-inflammatory drugs (NSAID) for use as a chemoprevention agent for colorectal cancer. Its use is associated with a 40% to 50% response rate for reduction in adenomatous polyps. However, rare serious cardiovascular effects and even death with celecoxib and other NSAIDs make it important to understand why some patients respond and others do not. Celecoxib is a selective inhibitor of COX-2. Its anticancer mechanism has largely been attributed to the inhibition of COX-2. Celecoxib also shows activity to induce apoptosis in cancer cells not expressing COX-2. This includes activity to upregulate 15-lipoxygenase-1 (15-LOX-1) independent of COX-2 and increase the synthesis of 13-S-hydroxyoctadecadienoic acid (13-S-HODE) from linoleic acid (LA) to downregulate PPAR-δ and induce apoptosis in colorectal cancer models. In examining the effect of celecoxib on 15-LOX-1 for reducing adenomatous polyps in patients with familial adenomatous polyposis (FAP), Yang and colleagues point out the potential importance of drug bioavailability in blood, normal, and neoplastic colorectal tissue in patient response. See related article, p. 217.

Computational dosimetry in MRI in presence of hip, knee or shoulder implants: do we need accurate surgery models?

Objective.To quantify the effects of different levels of realism in the description of the anatomy around hip, knee or shoulder implants when simulating, numerically, radiofrequency and gradient-induced heating in magnetic resonance imaging. This quantification is needed to define how precise the digital human model modified with the implant should be to get realistic dosimetric assessments.Approach. The analysis is based on a large number of numerical simulations where four 'levels of realism' have been adopted in modelling human bodies carrying orthopaedic implants.Main results. Results show that the quantification of the heating due to switched gradient fields does not strictly require a detailed local anatomical description when preparing the digital human model carrying an implant. In this case, a simple overlapping of the implant CAD with the body anatomy is sufficient to provide a quite good and conservative estimation of the heating. On the contrary, the evaluation of the electromagnetic field distribution and heating caused by the radiofrequency field requires an accurate description of the tissues around the prosthesis.Significance. The results of this paper provide hints for selecting the 'level of realism' in the definition of the anatomical models with embedded passive implants when performing simulations that should reproduce, as closely as possible, thein vivoscenarios of patients carrying orthopaedic implants.

Feasibility Trial to Evaluate Tendon Stiffness Obtained from Shear Wave Elastography Imaging as a Biomarker of Aromatase Inhibitor-Induced Arthralgias.

Aromatase inhibitor-induced arthralgia (AIA) comprises significant, activity-limiting musculoskeletal symptoms, including joint pain, myalgia, and joint stiffness. We conducted a prospective feasibility study in postmenopausal women diagnosed with early-stage (0-3) hormone receptor positive (HR+) breast cancer who were candidates for treatment with adjuvant AI therapy (n = 16). Tendons of the hands and wrists and the median nerve were imaged using gray-scale and power Doppler ultrasound (US) and US SWE. Arthralgia symptoms were evaluated using the Breast Cancer Prevention Trial (BCPT) Symptom Checklist musculoskeletal subscale (MS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and stiffness subscales. At baseline, there were significant differences in the SW velocities of tendons between dominant and nondominant hands. Increased velocity in 2 of 6 tendons and the median nerve was associated with greater pain at baseline, whereas slower velocity of the extensor digitorum tendon (suggesting decreased stiffness) was associated with a higher WOMAC stiffness score. Increased SW velocity (suggestive of increased stiffness) at baseline in the abductor pollicis longus tendon was associated with a worsening of all three pain and stiffness measures by 6 months. Future studies should evaluate SWE scores related to AIA outcomes in a larger sample size.

Evaluation of Patient Positioning to Mitigate RF-induced Heating of Cardiac Implantable Electronic Devices for Pediatric MRI Exams.

Pediatric patients with cardiac implantable electronic devices (CIEDs) are generally contraindicated for MRI exams. Previous work in the adult population suggests that RF-induced lead-tip heating strongly depends on the patient's position and orientation within the MRI scanner. The objective of this work was to evaluate the local Specific Absorption Rate (local-SAR) in silico for several pediatric patient positions within the MRI scanner as a method to potentially mitigate RF-heating lead-tip heating of CIEDs.

Shear wave elastography detects novel imaging biomarkers of aromatase inhibitor-induced joint pain: a pilot study.

AIM: To determine whether differences in joint and tendon stiffness as measured by ultrasound shear wave elastography are present in breast cancer patients with aromatase inhibitor-associated arthralgias compared to age-comparable healthy control women. METHODS: Postmenopausal women with stage I-III breast cancer who were taking adjuvant aromatase inhibitors and complained of joint pain were enrolled (n = 6). Postmenopausal women with no history of breast cancer, hormone treatment, or joint pain served as controls (n = 7). All subjects had bilateral hands and wrists evaluated by gray-scale and power Doppler ultrasound, and shear wave elastography ultrasound. RESULTS: Patients with AI-associated arthralgias had significantly stiffer tendons than controls in the 1st extensor compartment (long axis; p = 0.001), 4th extensor compartment (long axis; p = 0.014), 3rd metacarpophalangeal joint (p = 0.002), the pooled values of the extensor compartments, both long (p = 0.044) and short axes (p = 0.035), and the pooled values for the metacarpophalangeal joints (p = 0.002). On ultrasound, the patients (but not controls) presented with hyperemia and increased tenosynovial fluid in the flexor and extensor tendon sheaths, and the median nerves were symptomatic and bifid; however, these differences were not statistically significant. CONCLUSIONS: This is the first study to identify increased tendon stiffness as a putative physiological characteristic of aromatase inhibitor-associated arthralgias. Future studies should determine whether increased tendon stiffness is a risk factor for the development of aromatase inhibitor-associated arthralgias, or a result of aromatase inhibitor treatment.

A Protective Role for Arachidonic Acid Metabolites against Advanced Colorectal Adenoma in a Phase III Trial of Selenium.

Oxylipins derived from arachidonic acid (ARA) have been implicated in the development of colorectal adenomas and colorectal cancer. The primary purpose of this work was to determine the relationship between plasma levels of oxylipins and colorectal adenoma characteristics at study entry, as well as with the development of a new adenoma during follow-up within a Phase III adenoma prevention clinical trial with selenium (Sel). Secondarily, we sought to determine whether the selenium intervention influenced plasma oxylipin levels. Four oxylipins were quantified in stored plasma samples from a subset of Sel study subjects (n = 256) at baseline and at 12-months. There were significantly lower odds of an advanced adenoma at baseline with higher prostaglandin E2 (PGE2), with an OR (95% CI) of 0.55 (0.33-0.92), and with 5-hydroxyeicosatetraenoic acid (5-HETE) ((0.53 (0.33-0.94)); and of a large adenoma with higher PGE2 ((0.52 (0.31-0.87)). In contrast, no associations were observed between any oxylipin and the development of a new adenoma during follow-up. Selenium supplementation was associated with a significantly smaller increase in 5-HETE after 12 months compared to the placebo, though no other results were statistically significant. The ARA-derived oxylipins may have a role in the progression of non-advanced adenoma to advanced, but not with the development of a new adenoma.