Making Informed Choices On Incorporating Chemoprevention into carE (MiCHOICE, SWOG 1904): Design and methods of a cluster randomized controlled trial.

INTRODUCTION: Women with atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS) have a significantly increased risk of breast cancer, which can be substantially reduced with antiestrogen therapy for chemoprevention. However, antiestrogen therapy for breast cancer risk reduction remains underutilized. Improving knowledge about breast cancer risk and chemoprevention among high-risk patients and their healthcare providers may enhance informed decision-making about this critical breast cancer risk reduction strategy. METHODS/DESIGN: We are conducting a cluster randomized controlled trial to evaluate the effectiveness and implementation of patient and provider decision support tools to improve informed choice about chemoprevention among women with AH or LCIS. We have cluster randomized 26 sites across the U.S. through the SWOG Cancer Research Network. A total of 415 patients and 200 healthcare providers are being recruited. They are assigned to standard educational materials alone or combined with the web-based decision support tools. Patient-reported and clinical outcomes are assessed at baseline, after a follow-up visit at 6 months, and yearly for 5 years. The primary outcome is chemoprevention informed choice after the follow-up visit. Secondary endpoints include other patient-reported outcomes, such as chemoprevention knowledge, decision conflict and regret, and self-reported chemoprevention usage. Barriers and facilitators to implementing decision support into clinic workflow are assessed through patient and provider interviews at baseline and mid-implementation. RESULTS/DISCUSSION: With this hybrid effectiveness/implementation study, we seek to evaluate if a multi-level intervention effectively promotes informed decision-making about chemoprevention and provide valuable insights on how the intervention is implemented in U.S. TRIAL REGISTRATION: NCT04496739.

Long-Term Imaging Follow-up from the Management of Myelomeningocele Study.

BACKGROUND AND PURPOSE: Short-term results demonstrate that prenatal repair of a myelomeningocele is associated with a reduction in hydrocephalus and an increased likelihood of the reversal of Chiari II malformations compared with postnatal repair. The purpose of this study was to identify the long-term imaging findings at school age among subjects who underwent pre- versus postnatal repair of a myelomeningocele. MATERIALS AND METHODS: A subset of subjects enrolled in the Management of Myelomeningocele Study who underwent either prenatal (n = 66) or postnatal (n = 63) repair of a lumbosacral myelomeningocele and had follow-up brain MR imaging at school age were included. The prevalence of posterior fossa features of Chiari II malformation and supratentorial abnormalities and the change in these findings from fetal to school-age MR imaging were compared between the 2 groups. RESULTS: Prenatal repair of a myelomeningocele was associated with higher rates of normal location of fourth ventricle and lower rates of hindbrain herniation, cerebellar herniation, tectal beaking, brainstem distortion, and kinking at school age compared with postnatal repair (all P < .01). Supratentorial abnormalities, including corpus callosal abnormalities, gyral abnormalities, heterotopia, and hemorrhage, were not significantly different between the 2 groups (all P > .05). The rates of resolution of brainstem kinking, tectal beaking, cerebellar and hindbrain herniation, and normalization of fourth ventricle size from fetal to school age MR imaging were higher among the prenatal compared with postnatal surgery group (all, P < .02). CONCLUSIONS: Prenatal repair of a myelomeningocele is associated with persistent improvement in posterior fossa imaging findings of Chiari II malformation at school age compared with postnatal repair.

Exploratory Multisite MR Spectroscopic Imaging Shows White Matter Neuroaxonal Loss Associated with Complications of Type 1 Diabetes in Children.

BACKGROUND AND PURPOSE: Type 1 diabetes affects over 200,000 children in the United States and is associated with an increased risk of cognitive dysfunction. Prior single-site, single-voxel MRS case reports and studies have identified associations between reduced NAA/Cr, a marker of neuroaxonal loss, and type 1 diabetes. However, NAA/Cr differences among children with various disease complications or across different brain tissues remain unclear. To better understand this phenomenon and the role of MRS in characterizing it, we conducted a multisite pilot study. MATERIALS AND METHODS: In 25 children, 6-14 years of age, with type 1 diabetes across 3 sites, we acquired T1WI and axial 2D MRSI along with phantom studies to calibrate scanner effects. We quantified tissue-weighted NAA/Cr in WM and deep GM and modeled them against study covariates. RESULTS: We found that MRSI differentiated WM and deep GM by NAA/Cr on the individual level. On the population level, we found significant negative associations of WM NAA/Cr with chronic hyperglycemia quantified by hemoglobin A1c (P < .005) and a history of diabetic ketoacidosis at disease onset (P < .05). We found a statistical interaction (P < .05) between A1c and ketoacidosis, suggesting that neuroaxonal loss from ketoacidosis may outweigh that from poor glucose control. These associations were not present in deep GM. CONCLUSIONS: Our pilot study suggests that MRSI differentiates GM and WM by NAA/Cr in this population, disease complications may lead to neuroaxonal loss in WM in children, and deeper investigation is warranted to further untangle how diabetic ketoacidosis and chronic hyperglycemia affect brain health and cognition in type 1 diabetes.

Noncontrast MRI Protocol for Selected Pediatric Pituitary Endocrinopathies: A Procedure with High Diagnostic Yield and Potential to Reduce Anesthesia and Gadolinium-Based Contrast Exposure.

BACKGROUND AND PURPOSE: Although many pediatric neuroradiology practices empirically use noncontrast brain and pituitary MR imaging for evaluation of growth hormone deficiency, central precocious puberty, and short stature, there are currently insufficient published data to support this practice in an evidence-based fashion. Therefore, the use of contrast-enhanced MR imaging for all pediatric pituitary endocrinopathies remains widespread. We evaluated whether noncontrast MR imaging has adequate diagnostic yield for the evaluation of pediatric growth hormone deficiency, central precocious puberty, and short stature. MATERIALS AND METHODS: Pituitary MR imaging studies obtained for growth hormone deficiency, central precocious puberty, or short stature in patients 0-18 years of age from 2010 to 2019 were analyzed. Separate blinded review of noncontrast images in cases with abnormalities on the original radiology report was performed by 2 subspecialty-trained pediatric neuroradiologists, with discrepancies resolved by consensus. RESULTS: Of the 134/442 MR imaging studies obtained for growth hormone deficiency, central precocious puberty, or short stature with hypothalamic-pituitary region abnormalities, there was 70% concordance with the original reports on blinded review of noncontrast images. Twenty-two of 40 discrepancies were deemed unrelated to the indication, and 9 cases originally interpreted as possible microadenoma were read as having normal findings on blinded review. Only 9 of 40 discrepancies required contrast for further characterization. CONCLUSIONS: In our study, most relevant radiologic findings in patients with growth hormone deficiency, central precocious puberty, and short stature were detectable without contrast, providing evidence that contrast can be avoided in routine MR imaging evaluation of these indications. We propose a "rapid noncontrast pituitary" MR imaging protocol for pediatric patients presenting with growth hormone deficiency, central precocious puberty, or short stature, which may increase efficiency and decrease contrast and anesthesia exposure.

Diffuse Leptomeningeal Glioneuronal Tumor of Childhood.

Diffuse leptomeningeal glioneuronal tumor is a newly defined entity under the neuronal and mixed neuronal-glial tumors category in the 2016 World Health Organization classification of brain tumors. In this series, we report clinical, radiologic, and histologic findings in 7 cases of diffuse leptomeningeal glioneuronal tumor. Our cases and literature review indicate that the most characteristic imaging finding is diffuse intracranial and intraspinal nodular leptomeningeal thickening and enhancement. This is often associated with small cyst-like, nonenhancing lesions. It should be noted that tumors sometimes bear nontypical features, for example, presenting as a solitary spinal cord mass without leptomeningeal involvement or with a dominant intracranial mass. In children with characteristic imaging findings and without clinical features of infection, the radiologist has an opportunity to promptly raise the possibility of diffuse leptomeningeal glioneuronal tumor, and thereby, affect streamlined diagnostic evaluation.

Human Parechovirus Meningoencephalitis: Neuroimaging in the Era of Polymerase Chain Reaction-Based Testing.

Human parechovirus infection is an increasingly recognized cause of neonatal meningoencephalitis. We describe characteristic clinical features and brain MR imaging abnormalities of human parechovirus meningoencephalitis in 6 infants. When corroborated by increasingly available polymerase chain reaction-based testing of the CSF, the distinctive MR imaging appearance may yield a specific diagnosis that obviates costly and time-consuming further clinical evaluation. In our study, infants with human parechovirus presented in the first 35 days of life with seizures, irritability, and sepsis. MR imaging consistently demonstrated low diffusivity within the thalami, corpus callosum, and subcortical white matter with a frontoparietal predominance. T1 and T2 shortening connoting white matter injury along the deep medullary veins suggests venous ischemia as an alternative potential pathogenetic mechanism to direct neuroaxonal injury.

Basic and advanced echocardiographic evaluation of myocardial dysfunction in sepsis and septic shock.

Sepsis continues to be a leading cause of mortality and morbidity in the intensive care unit. Cardiovascular dysfunction in sepsis is associated with worse short- and long-term outcomes. Sepsis-related myocardial dysfunction is noted in 20%-65% of these patients and manifests as isolated or combined left or right ventricular systolic or diastolic dysfunction. Echocardiography is the most commonly used modality for the diagnosis of sepsis-related myocardial dysfunction. With the increasing use of ultrasonography in the intensive care unit, there is a renewed interest in sepsis-related myocardial dysfunction. This review summarises the current scope of literature focused on sepsis-related myocardial dysfunction and highlights the use of basic and advanced echocardiographic techniques for the diagnosis of sepsis-related myocardial dysfunction and the management of sepsis and septic shock.

Multigene expression profile testing in breast cancer: is there a role for family physicians?

BACKGROUND: Family physicians (fps) play a role in aspects of personalized medicine in cancer, including assessment of increased risk because of family history. Little is known about the potential role of fps in supporting cancer patients who undergo tumour gene expression profile (gep) testing. METHODS: We conducted a mixed-methods study with qualitative and quantitative components. Qualitative data from focus groups and interviews with fps and cancer specialists about the role of fps in breast cancer gep testing were obtained during studies conducted within the pan-Canadian canimpact research program. We determined the number of visits by breast cancer patients to a fp between the first medical oncology visit and the start of chemotherapy, a period when patients might be considering results of gep testing. RESULTS: The fps and cancer specialists felt that ordering gep tests and explaining the results was the role of the oncologist. A new fp role was identified relating to the fp-patient relationship: supporting patients in making adjuvant therapy decisions informed by gep tests by considering the patient's comorbid conditions, social situation, and preferences. Lack of fp knowledge and resources, and challenges in fp-oncologist communication were seen as significant barriers to that role. Between 28% and 38% of patients visited a fp between the first oncology visit and the start of chemotherapy. CONCLUSIONS: Our findings suggest an emerging role for fps in supporting patients who are making adjuvant treatment decisions after receiving the results of gep testing. For success in this new role, education and point-of-care tools, together with more effective communication strategies between fps and oncologists, are needed.

Improving Perfusion Measurement in DSC-MR Imaging with Multiecho Information for Arterial Input Function Determination.

BACKGROUND AND PURPOSE: Clinical measurements of cerebral perfusion have been increasingly performed with multiecho dynamic susceptibility contrast-MR imaging techniques due to their ability to remove confounding T1 effects of contrast agent extravasation from perfusion quantification. However, to this point, the extra information provided by multiecho techniques has not been used to improve the process of estimating the arterial input function, which is critical to accurate perfusion quantification. The purpose of this study is to investigate methods by which multiecho DSC-MRI data can be used to automatically avoid voxels whose signal decreases to the level of noise when calculating the arterial input function. MATERIALS AND METHODS: Here we compare postprocessing strategies for clinical multiecho DSC-MR imaging data to test whether arterial input function measures could be improved by automatically identifying and removing voxels exhibiting signal attenuation (truncation) artifacts. RESULTS: In a clinical pediatric population, we found that the Pearson correlation coefficient between ΔR2* time-series calculated from each TE individually was a valuable criterion for automated estimation of the arterial input function, resulting in higher peak arterial input function values while maintaining smooth and reliable arterial input function shapes. CONCLUSIONS: This work is the first to demonstrate that multiecho information may be useful in clinically important automatic arterial input function estimation because it can be used to improve automatic selection of voxels from which the arterial input function should be measured.

Hormone therapy for management of menopausal symptoms: understanding [corrected] breast cancer risk.

Since the publication of the Women's Health Initiative, women seeking relief from menopausal symptoms often express concerns about the risk of hormone therapy (HT). In women at increased risk for breast cancer or with a personal history of breast cancer, the decision to use HT for the treatment of menopausal symptoms must be carefully considered in the context of the most recent literature. It is well established that HT is the most effective treatment for climacteric symptoms and sexual dysfunction. The evidence to date on the use of HT in women with a history of breast cancer is complicated by the fact that the majority of breast cancers are estrogen responsive and the concern about risk of recurrence. Over the past decade, survival after breast cancer treatment has continued to improve resulting in millions of survivors worldwide. As a result of breast cancer therapies, the prevalence of menopausal symptoms is increasing in survivors, and both clinicians and patients are seeking safe and effective therapies for symptom management. This article will review the role of HT in the treatment of menopausal symptoms in women without breast cancer and those with a personal history of breast cancer or those who are at increased risk of breast cancer. Management of menopause-related symptoms will be reviewed with a focus on strategies to improve quality of life.

Unusual radiographic appearance of drug-induced pharyngeal angioedema and differential considerations.

A 59-year-old woman treated chronically with enalapril, an angiotensin-converting enzyme inhibitor (ACE-I) presented with difficult swallowing and speaking. Although her symptoms were clinically consistent with an adverse angioedema reaction to the ACE-I, initial imaging was not entirely consistent with our conceptual understanding of angioedema. This case report will discuss the myriad possible imaging presentations of this disease, as well as the differential diagnosis for this atypical manifestation of ACE-I-induced angioedema.

Vitamin E supplementation in the prevention of coronary heart disease.

Vitamin E consists of a number of compounds, tocopherols and tocotrienols, that function as lipid-soluble antioxidants. A hypothesis is that vitamin E may slow the progression of atherosclerosis by blocking the oxidative modification of low-density lipoprotein cholesterol and thus decrease its uptake into the arterial lumen. Basic science and animal studies have generally supported this hypothesis. Observational studies have primarily assessed patients with no established coronary heart disease (CHD), and results have generally supported a protective role of vitamin E in CHD. Early primary and secondary prevention clinical trials (Alpha-Tocopherol, Beta-Carotene Cancer Protection study and Cambridge Heart Antioxidant Study) showed mixed results. Despite years of encouraging evidence from basic science and observational studies, 3 large randomized clinical trials (Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico, Heart Outcomes Prevention Evaluation, and Primary Prevention Project) with a combined total of more than 25,000 patients failed to show a significant benefit with vitamin E taken as a dietary supplement for the prevention of CHD. Four large randomized primary prevention trials currently under way should add to our knowledge. The American Heart Association has recommended consumption of a balanced diet with emphasis on antioxidant-rich fruits and vegetables but has made no recommendations regarding vitamin E supplementation for the general population. Although vitamin E supplementation seems to be safe for most people, recommendations from health care professionals should reflect the uncertainty of established benefit as demonstrated in clinical trials.

Detection and evaluation of a palpable breast mass.

The discovery of a breast mass, either self-detected or identified by a clinician, is a common, often distressing occurrence for many women. Although most detected breast masses are benign, every woman presenting with a breast mass should be evaluated to exclude or establish a diagnosis of cancer. This article provides a succinct overview of normal breast anatomy and reviews common causes of breast masses. The role of the clinical breast examination is discussed, and an algorithm is provided for optimal utilization of available tools in the diagnostic evaluation of a breast mass. The evaluation should be performed expeditiously and the results communicated promptly to the patient. Regardless of the age of the woman, a clinically suspicious mass must be evaluated even if findings on a mammogram are normal.

Tamoxifen in the management of pseudoangiomatous stromal hyperplasia.

Pseudoangiomatous stromal hyperplasia (PASH) is a relatively uncommon histologic finding in breast specimens. The clinicopathologic spectrum of this disease entity can range from a focal nonsignificant microscopic finding to a dominant palpable breast mass. To confirm the diagnosis, a biopsy is required primarily to distinguish PASH from a low-grade angiosarcoma. The mammographic description of PASH is a round or ovoid, circumscribed or partially circumscribed mass. The sonographic feature is a hypoechoic mass. PASH is similar to a fibroadenoma in clinical and imaging features. Progressive breast enlargement associated with engorgement, cyclical breast pain, and burning sensation is of significant concern for some women. The management of the palpable mass and associated symptoms has included excisional biopsy, often leading to recurrent excisions and even mastectomy. This report documents an impressive response to tamoxifen in a patient with PASH presenting with breast enlargement, pain, and breast masses. To our knowledge, there are no reports on the use of tamoxifen or other selective estrogen receptor modulators in the management of this benign breast condition.

Hypertensive retinopathy mimicking neuroretinitis in a twelve-year-old girl.

Bilateral disk swelling and marked peripapillary and macular exudates were found on routine ophthalmologic examination in a 12 1/2-year-old girl. Eleven months later, with persistent findings, her blood pressure was found to be extremely elevated. She had an Ask-Upmark kidney, a rare form of segmental renal hypoplasia. The Ask-Upmark kidney abnormality occurs primarily in young women and is associated with hypertension. The disk edema and retinopathy resolved after the hypertension was controlled. Hypertensive retinopathy can sometimes resemble neuroretinitis.