Decitabine induction with myeloablative conditioning and allogeneic hematopoietic stem cell transplantation in high-risk patients with myeloid malignancies is associated with a high rate of infectious complications.

Patients with high-risk myelodysplastic syndrome or acute myeloid leukemia have an increased risk of death following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Decitabine has minimal non-hematologic toxicity and proven efficacy in myeloid diseases, and post-transplant cyclophosphamide (PTCy) has reduced rates of graft-versus-host-disease (GVHD). We hypothesized that decitabine induction with allo-HSCT and PTCy would improve outcomes in a high-risk myeloid disease population. We performed a phase-II trial of decitabine at 20 mg/m2 for 10 days followed by allo-HSCT using a myeloablative regimen of fludarabine, IV busulfan and 4 Gy total body irradiation with PTCy for GVHD prophylaxis. Twenty patients underwent decitabine induction and 17 patients proceeded to transplant per protocol. Median overall survival from decitabine induction was 210 days (95 % CI 122-not reached). All patients developed grade 4 neutropenia after decitabine, eleven patients (55 %) developed grade 3-4 infections, and 5 cases were fatal. There were 5/20 (25 %) long-term survivors with a median follow-up of 3.6 years. Decitabine induction followed by myeloablative allo-HSCT in a high-risk population was associated with a high risk of infection and mortality related to enhanced immunosuppression. Further exploration of decitabine conditioning on reduced intensity platforms and improved infectious prophylaxis and screening may better mitigate toxicity (ClinicalTrials.gov (NCT01707004)).

A digital media attention diversion improves mood and fear in patients receiving chemotherapy for recurrent gynecologic malignancies: results of a randomized trial.

BACKGROUND: Recurrent gynecologic cancer patients experience symptoms that affect psychologic, emotional, social, and physical well-being. Chemotherapy can further exacerbate these symptoms. Poor mood, pain, and fatigue are linked and are detrimental to quality of life. Interventions targeting these symptoms may improve patient-reported outcomes and performance status. OBJECTIVES: To determine the ability of a humorous digital media attention diversion to improve symptom domains of positive and negative mood during chemotherapy for patients with recurrent gynecologic cancers. STUDY DESIGN: This randomized, crossover clinical trial enrolled women with recurrent gynecologic cancers. Subjects participated over three cycles of chemotherapy. The primary outcome was the change in mood on the validated Positive and Negative Affect Scale-Extended (PANAS-X) instrument, which measures positive and negative affect domains. All subjects completed the PANAS-X after receiving chemotherapy during cycle 1 on study. In atudy arm 1, subjects watched their choice of humorous movies on a digital media device while receiving chemotherapy during cycle 2 on study. They selected from non-humorous movies during cycle 3 on study. In arm 2, the order of movies was reversed. After each cycle, mood, fatigue, and other patient-reported outcomes were assessed for comparison with baseline measurements. RESULTS: The target enrollment of 66 subjects was achieved. Subjects watched humorous content for an average of 96.0 min and non-humorous content for an average of 62.5 min. Negative mood improved after exposure to humorous (p=0.017) and non-humorous content (p=0.001). Patient-reported fear also improved after exposure to both humorous (p=0.038) and non-humorous content (p=0.002). Subjects reported higher use of affiliating and self-effacing humor types. CONCLUSIONS: Offering patients a choice of digital media during chemotherapy significantly improved negative mood and fear. This was seen with both humorous and non-humorous content. This low-cost and low-risk intervention should be implemented as an attention diversion to improve negative mood and fear for patients receiving chemotherapy.

Combined gadoxetic acid and gadobenate dimeglumine enhanced liver MRI: a parameter optimization study.

PURPOSE: To demonstrate the feasibility of combined delayed-phase gadoxetic acid (GA) and gadobenate dimeglumine (GD) enhanced liver MRI for improved detection of liver metastases, and to optimize contrast agent dose, timing, and flip angle (FA). METHODS: Fourteen healthy volunteers underwent liver MRI at 3.0T at two visits during which they received two consecutive injections: 1. GA (Visit 1 = 0.025 mmol/kg; Visit 2 = 0.05 mmol/kg) and 2. GD (both visits = 0.1 mmol/kg) 20 min after GA administration. Two sub-studies were performed: Experiment-1 Eight subjects underwent multi-phase breath-held 3D-fat-saturated T1-weighted spoiled gradient echo (SGRE) imaging to determine the optimal imaging window for the combined GA + GD protocol to create a homogeneously hyperintense liver and vasculature ("plain-white-liver") with maximum contrast to muscle which served as a surrogate for metastatic lesions in both experiments. Experiment-2 Six subjects underwent breath-held 3D-fat-saturated T1-weighted SGRE imaging at three different FA to determine the optimal FA for best image contrast. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were evaluated. RESULTS: Experiment-1 The combined GA + GD protocol created a homogeneously hyperintense liver and vasculature with maximum CNR liver/muscle at approximately 60-120 s after automatic GD-bolus detection. Experiment-2 Flip angles between 25° and 35° at a dose of 0.025 mmol/kg GA provided the best combination that minimized liver/vasculature CNR, while maximizing liver/muscle CNR. CNR performance to achieve a "plain-white-liver" was superior with 0.025 mmol/kg GA compared to 0.05 mmol/kg. CONCLUSION: Combined GA + GD enhanced T1-weighted MRI is feasible to achieve a homogeneously "plain-white-liver". Future studies need to confirm that this protocol can improve sensitivity of liver lesion detection in patients with metastatic liver disease.

Pharmacokinetics of Ferumoxytol in the Abdomen and Pelvis: A Dosing Study with 1.5- and 3.0-T MRI Relaxometry.

Background The off-label use of ferumoxytol (FE), an intravenous iron preparation for iron deficiency anemia, as a contrast agent for MRI is increasing; therefore, it is critical to understand its pharmacokinetics. Purpose To evaluate the pharmacokinetics of FE in the abdomen and pelvis, as assessed with quantitative 1.5- and 3.0-T MRI relaxometry. Materials and Methods R2*, an MRI technique used to estimate tissue iron content in the abdomen and pelvis, was performed at 1.5 and 3.0 T in 12 healthy volunteers between April 2015 and January 2016. Volunteers were randomly assigned to receive an FE dose of 2 mg per kilogram of body weight (FE2mg) or 4 mg/kg (FE4mg). MRI was repeated at 1.5 and 3.0 T for each volunteer at five time points: days 1, 2, 4, 7, and 30. A radiologist experienced in MRI relaxometry measured R2* in organs of the mononuclear phagocyte system (MPS) (ie, liver, spleen, and bone marrow), non-MPS anatomy (kidney, pancreas, and muscle), inguinal lymph nodes (LNs), and blood pool. A paired Student t test was used to compare changes in tissue R2*. Results Volunteers (six female; mean age, 44.3 years ± 12.2 [standard deviation]) received either FE2 mg (n = 5) or FE4 mg (n = 6). Overall R2* trend analysis was temporally significant (P < .001). Time to peak R2* in the MPS occurred on day 1 for FE2mg and between days 1 and 4 for FE4mg (P < .001 to P < .002). Time to peak R2* in non-MPS anatomy, LNs, and blood pool occurred on day 1 for both doses (P < .001 to P < .09). Except for the spleen (at 1.5 T) and liver, MPS R2* remained elevated through day 30 for both doses (P = .02 to P = .03). Except for the kidney and pancreas, non-MPS, LN, and blood pool R2* returned to baseline levels between days 2 and 4 at FE2mg (P = .06 to P = .49) and between days 4 and 7 at FE4mg (P = .06 to P = .63). There was no difference in R2* change between non-MPS and LN R2* at any time (range, 1-71 sec-1 vs 0-50 sec-1; P = .06 to P = .97). Conclusion The pharmacokinetics of ferumoxytol in lymph nodes are distinct from those in mononuclear phagocyte system (MPS) organs, parallel non-MPS anatomy, and the blood pool. © RSNA, 2019 Online supplemental material is available for this article.

Validation of an epigenetic field of susceptibility to detect significant prostate cancer from non-tumor biopsies.

BACKGROUND: An epigenetic field of cancer susceptibility exists for prostate cancer (PC) that gives rise to multifocal disease in the peripheral prostate. In previous work, genome-wide DNA methylation profiling identified altered regions in the normal prostate tissue of men with PC. In the current multicenter study, we examined the predictive strength of a panel of loci to detect cancer presence and grade in patients with negative biopsy tissue. RESULTS: Four centers contributed benign prostate biopsy tissues blocks from 129 subjects that were either tumor associated (TA, Grade Group [GG] ≥ 2, n = 77) or non-tumor associated (NTA, n = 52). Biopsies were analyzed using pyrosequencing for DNA methylation encompassing CpG loci near CAV1, EVX1, FGF1, NCR2, PLA2G16, and SPAG4 and methylation differences were detected within all gene regions (p < 0.05). A multiplex regression model for biomarker performance incorporating a gene combination discriminated TA from NTA tissues (area under the curve [AUC] 0.747, p = 0.004). A multiplex model incorporating all the above genes and clinical information (PSA, age) identified patients with GG ≥ 2 PC (AUC 0.815, p < 0.0001). In patients with cancer, increased variation in gene methylation levels occurs between biopsies across the prostate. CONCLUSIONS: A widespread epigenetic field defect is utilized to detect GG ≥ 2 PC in patients with histologically negative biopsies. These alterations in non-tumor cells display increased heterogeneity of methylation extent and are spatially distant from tumor foci. These findings have the potential to decrease the need for repeated prostate biopsy.

Incidence and implications of fracture in core muscle injury.

OBJECTIVE: To determine the pubic bone fracture incidence and associated injury patterns in patients with core muscle injury. MATERIALS AND METHODS: Ninety-three consecutive patients with core muscle injury protocol MRI showing rectus abdominis-adductor longus aponeurotic plate injuries from June 2007 through August 2017 were independently analyzed in blinded fashion by two musculoskeletal radiologists for the presence or absence of pubic bone fracture. A variety of other osseous and soft tissue injury characteristics were recorded. Pain duration prior to MRI and return to play time were taken from the clinical record. Statistical analysis included fracture incidence as well as the association of fracture with other injury characteristics, duration of pain, and return to play time. RESULTS: Eighty-seven men and six women with a mean age of 34.4 years (range, 16-66 years) were included in the study cohort. Overall fracture incidence was 18.3% (17/93) including 13 fatigue fractures of the pubic body and four elevated cortical fractures/fragments. After correction for multiple comparisons, no strong association was identified with osseous or soft tissue injury characteristics, pain duration, or return to play time. CONCLUSIONS: Pubic fractures-particularly fatigue fractures-are a common co-existing injury in patients with a wide range of core muscle injury patterns. The presence of fracture did not have a strong correlation with injury patterns, pain duration, or return to play time but may have implications for patient management.

Collagen organization of renal cell carcinoma differs between low and high grade tumors.

BACKGROUND: The traditional pathologic grading for human renal cell carcinoma (RCC) has low concordance between biopsy and surgical specimen. There is a need to investigate adjunctive pathology technique that does not rely on the nuclear morphology that defines the traditional grading. Changes in collagen organization in the extracellular matrix have been linked to prognosis or grade in breast, ovarian, and pancreatic cancers, but collagen organization has never been correlated with RCC grade. In this study, we used Second Harmonic Generation (SHG) based imaging to quantify possible differences in collagen organization between high and low grades of human RCC. METHODS: A tissue microarray (TMA) was constructed from RCC tumor specimens. Each TMA core represents an individual patient. A 5 µm section from the TMA tissue was stained with standard hematoxylin and eosin (H&E). Bright field images of the H&E stained TMA were used to annotate representative RCC regions. In this study, 70 grade 1 cores and 51 grade 4 cores were imaged on a custom-built forward SHG microscope, and images were analyzed using established software tools to automatically extract and quantify collagen fibers for alignment and density assessment. A linear mixed-effects model with random intercepts to account for the within-patient correlation was created to compare grade 1 vs. grade 4 measurements and the statistical tests were two-sided. RESULTS: Both collagen density and alignment differed significantly between RCC grade 1 and RCC grade 4. Specifically, collagen fiber density was greater in grade 4 than in grade 1 RCC (p < 0.001). Collagen fibers were also more aligned in grade 4 compared to grade 1 (p < 0.001). CONCLUSIONS: Collagen density and alignment were shown to be significantly higher in RCC grade 4 vs. grade 1. This technique of biopsy sampling by SHG could complement classical tumor grading approaches. Furthermore it might allow biopsies to be more clinically relevant by informing diagnostics. Future studies are required to investigate the functional role of collagen organization in RCC.

Evaluation of suspected musculoskeletal infection in children over 2 years of age using only fluid-sensitive sequences at MRI.

PURPOSE: This study was conducted in order to evaluate whether an MRI protocol with only fluid-sensitive sequences can be used to evaluate for musculoskeletal (MSK) infection of the pelvis and limbs in children. MATERIALS AND METHODS: This retrospective study analyzed 90 contrast-enhanced (CE) MRI studies from 88 consecutive patients (52 boys and 36 girls; mean age 9 ± 4.3 years; range 2-17) that were performed for the clinical suspicion of MSK infection. Two radiologists reviewed each study twice. The initial study review included only the fluid-sensitive sequences (fluid-sensitive study); the second review, performed at least 1 month later, included all sequences of the contrast-enhanced study (CE study). At each review, anatomic sites of abnormal signal and overall suspicion for infection were recorded. Cohen's kappa and percent agreement were performed to compare agreement between readers, types of studies, and clinical diagnoses. RESULTS: Interreader agreement for both types of studies had kappa values between 0.86 and 1. For the assessment of MSK infection, the fluid-sensitive study had 100% sensitivity and 61.3% specificity, with 84.8% interreader agreement; and the CE study had 100% sensitivity and 71.0% specificity, with 88.6% interreader agreement. All cases of septic arthritis (13 cases) and osteomyelitis (25 cases) were identified as possible infection or infection until proven otherwise (negative predictive value 100%) with 100% interreader agreement on fluid-sensitive sequences. CONCLUSION: An abbreviated MRI study using only fluid-sensitive sequences has the same high degree of sensitivity as a CE study to identify MSK infection in children and could be used to exclude septic arthritis and osteomyelitis. KEY POINTS: • MRI with only fluid-sensitive sequences can be used to evaluate for musculoskeletal infection in children.

International Survey on the Use of Complementary and Alternative Medicines for Common Toxicities of Radiation Therapy.

PURPOSE: Complementary and alternative medicines (CAMs) are widely used by patients with cancer. However, little is known about the extent to which these potential remedies are used internationally to treat the most common toxicities of radiation therapy. We report on the results of an international survey that assessed the use of CAMs. METHODS AND MATERIALS: Surveys were distributed to 1174 practicing radiation oncologists. Questions evaluated the perceptions of CAMs and specific practice patterns for the use of CAM remedies in the treatment of common radiation-induced toxicities (eg, skin, fatigue, nausea, diarrhea, and mucositis/xerostomia). The responses were compared between the groups using the χ2 test and stratified on the basis of provider location, number of years in practice, and perception of CAMs. RESULTS: A total of 114 radiation oncologists from 29 different countries completed the survey, with a balanced distribution between North American (n = 56) and non-North American (n = 58) providers. Among the responding clinicians, 63% recommended CAMs in their practice. The proportion of clinicians who recommend CAMs for radiation toxicities did not significantly vary when stratified by provider's number of years in practice (P = .23) or location (United States/Canada vs other; P = .74). Overall, providers reported that 29.4% of their patients use CAMs, and 87.7% reported that their practice encouraged or was neutral on CAM use, whereas 12.3% recommended stopping CAMs. The most common sources of patient information on CAMs were the Internet (75.4%), friends (60.5%), and family (58.8%). Clinicians reported the highest use of CAMs for radiation skin toxicity at 66.7%, followed by 48.2% for fatigue, 40.4% for nausea, and 36.8% for mucositis/xerostomia. CONCLUSIONS: Nearly two-thirds of the surveyed radiation oncologists recommend CAMs for radiation-related toxicities; however, they estimated that less than one third of patients use CAMs for this purpose. This suggests a need for further investigation and perhaps greater patient education on the roles of CAMs in treating radiation toxicities.

Granulocyte colony-stimulating factor utilization postautologous hematopoietic stem cell transplant in multiple myeloma patients: Does one size fit all?

PURPOSE: To evaluate a single institution's experience with granulocyte colony-stimulating factor after autologous hematopoietic stem cell transplant in myeloma patients to identify populations that benefit most from granulocyte colony-stimulating factor administration. METHODS: Retrospective chart reviews were conducted on patients 18+ years with multiple myeloma that underwent autologous hematopoietic stem cell transplant at UW Health from January 2012 to May 2016. Data collection included demographics, length of stay, time to engraftment, Eastern Cooperative Oncology Group performance status score, and hematopoietic cell transplantation-comorbidity index. The primary outcome was days from transplant to engraftment, defined as absolute neutrophil count > 500/mm3 for two consecutive days or absolute neutrophil count > 1000/mm3 once. A subset analysis was performed on patients whose date of engraftment was known. RESULTS: In total, 216 individual patients were included in the full cohort and 122 patients included in the subset analysis. Median time to engraftment between patients administered granulocyte colony-stimulating factor and the nongranulocyte colony-stimulating factor group was 12 versus 19 days (P < 0.001) in the full cohort and 12 versus 14 days (P < 0.001) in the subset analysis. The average length of stay posthematopoietic stem cell transplant in the granulocyte colony-stimulating factor group was 15 days versus 17 days in the nongranulocyte colony-stimulating factor group (P = 0.026) in the subset analysis. Additionally, no difference in time to engraftment was seen when stratified by age, Eastern Cooperative Oncology Group performance status score, or hematopoietic cell transplantation-comorbidity index. CONCLUSION: Our study supports use of granulocyte colony-stimulating factor posthematopoietic stem cell transplant in myeloma patients to decrease time to engraftment and length of stay. Consideration should be given to utilization in all patients in this population posthematopoietic stem cell transplant. Further research is needed to identify the populations that benefit most from granulocyte colony-stimulating factor administration.

Disparities in the allocation of research funding to gynecologic cancers by Funding to Lethality scores.

PURPOSE: To analyze National Cancer Institute (NCI) funding distributions to gynecologic cancers compared to other cancers from 2007 to 2014. METHODS: The NCI's Surveillance, Epidemiology and End Results (SEER), Cancer Trends Progress Report, and Funding Statistics were used to analyze 18 cancer sites. Site-specific mortality to incidence ratios (MIR) were normalized per 100 cases and multiplied by person-years of life lost to derive cancer-specific lethality. NCI funding was divided by its lethality to calculate Funding to Lethality scores for gynecologic malignancies and compared to 15 other cancer sites. RESULTS: Ovarian, cervical, and uterine cancers ranked 10th (score 0.097, SD 0.008), 12th (0.087, SD 0.009), and 14th (0.057, SD 0.006) for average Funding to Lethality scores. The highest average score was for prostate cancer (score 1.182, SD 0.364). In U.S. dollars per 100 incident cases, prostate cancer received an average of $1,821,000 per person-years of life lost, while ovarian cancer received $97,000, cervical cancer $87,000, and uterine cancer $57,000. Ovarian and cervical cancers had lower average Funding to Lethality scores compared to nine other cancers, while uterine cancer was lower than 13 other cancers (p < 0.01 for all comparisons). Analyses of eight-, five-, and three-year trends for gynecologic cancers showed nearly universal decreasing Funding to Lethality scores. CONCLUSION: Funding to Lethality scores for gynecologic cancers are significantly lower than other cancer sites, indicating a disparity in funding allocation that persists over the most recent eight years of available data. Prompt correction is required to ensure critical discoveries for women with gynecologic cancers.

An analysis of factors associated with increased fluoroscopy time or the need for complex techniques at IVC filter retrieval.

OBJECTIVES: To evaluate factors associated with increased fluoroscopy time or the need for complex techniques at IVC filter retrieval. METHODS: This is a single-institution retrospective cohort study of 187 consecutive patients who underwent IVC filter retrieval. An analysis was performed on associations of patient factors with increased fluoroscopy time and/or the need for complex retrieval techniques. A complex retrieval was defined as one requiring more than standard sheath and snare technique. RESULTS: Access vein during filter placement was not associated with filter tilt at placement or removal (p = 0.61 and 0.48). Neither the direction of the hook nor its relationship to the tilt was associated with the need for complex retrieval or increased retrieval fluoroscopy time (p = 0.25, 0.23, p = 0.18, 0.23). Tilt angle at placement correlated with hook apposition at time of removal (p = 0.01). Hook apposition was associated with complex retrieval and increased fluoroscopy time (p < 0.01). Larger tilt angle at placement was not associated with complex retrieval (p = 0.22), but a larger angle at removal was (p < 0.01). Longer dwell time correlated with the need for complex retrieval (p = 0.02). Filter type, sex, and age were not associated with complex retrievals (p = 0.58, p = 0.90, p = 0.99). CONCLUSION: Contrary to previous hypotheses and studies, access vein for filter placement did not affect filter tilting, and direction of filter hook-tilt relationship did not affect retrieval fluoroscopy time or the need for complex retrieval techniques. Increased filter placement angle was associated with a larger angle at removal and hook-wall apposition, both of which were associated with complex retrievals. KEY POINTS: • Filter hook orientation did not correlate with retrieval complexity. • Filter insertion vein did not correlate with filter tilt. • Filter tilt and hook apposition to the caval wall at the time of retrieval correlated with retrieval procedure complexity.

Procedure-Specific Risk Prediction for Recurrence in Patients Undergoing Lobectomy or Sublobar Resection for Small (≤2 cm) Lung Adenocarcinoma: An International Cohort Analysis.

INTRODUCTION: This work was performed to develop and validate procedure-specific risk prediction for recurrence following resection for early-stage lung adenocarcinoma (ADC) and investigate risk prediction utility in identifying patients who may benefit from adjuvant chemotherapy (ACT). METHODS: In patients who underwent resection for small (≤2 cm) lung ADC (lobectomy, 557; sublobar resection, 352), an association between clinicopathologic variables and risk of recurrence was assessed by a competing risks approach. Procedure-specific risk prediction was developed based on multivariable regression for recurrence. External validation was conducted using cohorts (N = 708) from Japan, Taiwan, and Germany. The accuracy of risk prediction was measured using a concordance index. We applied the lobectomy risk prediction approach to a propensity score-matched cohort of patients with stage II-III disease (n = 316, after matching) with or without ACT and compared lung cancer-specific survival between groups among low- or high-risk scores. RESULTS: Micropapillary pattern, solid pattern, lymphovascular invasion, and necrosis were involved in the risk prediction following lobectomy, and micropapillary pattern, spread through air spaces, lymphovascular invasion, and necrosis following sublobar resection. Both internal and external validation showed good discrimination (concordance index in lobectomy and sublobar resection: internal, 0.77 and 0.75, respectively; and external, 0.73 and 0.79, respectively). In the stage II-III propensity score-matched cohort, among high-risk patients, ACT significantly reduced the risk of lung cancer-specific death (subhazard ratio 0.43, p = 0.001), but not among low-risk patients. CONCLUSIONS: Procedure-specific risk prediction for patients with resected small lung ADC can be used to better prognosticate and stratify patients for further interventions.

Detection of pediatric musculoskeletal pathology using the fluid-sensitive sequence.

BACKGROUND: Musculoskeletal complaints are common among children, and magnetic resonance (MR) is increasingly used to supplement the clinical assessment. The validation of a short triage protocol could reduce the number of unnecessary contrast-enhanced MR studies that sometimes also require the need for sedation. OBJECTIVE: To compare the diagnostic accuracy between fluid-sensitive sequence and contrast-enhanced MR study in the detection of musculoskeletal pathology in the pelvis and the appendicular skeleton in children older than 2 years. MATERIALS AND METHODS: We performed a retrospective review between Feb. 1, 2016, and Oct. 31, 2016, and identified 99 studies from 96 patients (48 boys and 48 girls; mean age ± standard deviation, 11.1±4.6 years) without syndromic deformity, recent trauma, a history of infectious or inflammatory arthropathy, prior instrumentation or incomplete records. Two radiologists reviewed each study twice, at least 1 month apart, first using only the fluid-sensitive sequences (triage study) and later using the contrast-enhanced study. Readers rated the presence or absence of pathology independently and generated final impressions in consensus. We used Cohen's kappa (κ) and percentage agreement to compare agreement between readers and between studies, respectively. RESULTS: Inter-reader agreement was overall higher for the contrast-enhanced studies (κ range = 0.91-1) than for the triage studies (κ range = 0.49-1). Percentage agreement between studies was high for the detection of pathology (97-100%) and for the impressions (93%). Clinical diagnoses were stress reaction or overuse in 31%, infection in 21%, space-occupying process in 17%, normal in 15%, inflammatory in 14%, and both inflammatory and overuse in 1%. The full study increased diagnostic confidence in five studies and accuracy in two but did not alter management. CONCLUSION: The fluid-sensitive sequence had a near-perfect percentage of agreement with the contrast-enhanced study in the detection of musculoskeletal pathology and could possibly be used to screen children who need a contrast-enhanced MR study.

Maturation-Related Changes in T2 Relaxation Times of Cartilage and Meniscus of the Pediatric Knee Joint at 3 T.

OBJECTIVE: The objective of our study was to use a T2 mapping sequence performed at 3 T to investigate changes in the composition and microstructure of the cartilage and menisci of the pediatric knee joint during maturation. MATERIALS AND METHODS: This retrospective study was performed of MRI examinations of 76 pediatric knees without internal derangement in 72 subjects (29 boys [mean age, 12.5 years] and 43 girls [mean age, 13.0 years]) who were evaluated with a sagittal T2 mapping sequence. T2 relaxation time values were quantitatively measured in eight cartilage subregions and in the medial and lateral menisci. Wilcoxon rank sum and Kruskal-Wallis tests were used to analyze the relationship between cartilage and meniscus T2 relaxation time values and sex and skeletal maturation, respectively. A multivariate linear regression model was used to investigate the independent association between cartilage T2 relaxation time values and age, weight, and body mass index (BMI [weight in kilograms divided by the square of height in meters]). RESULTS: There were no significant sex differences (p = 0.26-0.91) in T2 relaxation time values for cartilage or meniscus. T2 relaxation time values in each individual cartilage subregion significantly decreased (p < 0.001) with progressive maturation. T2 relaxation time values in the lateral meniscus significantly increased (p = 0.001) with maturation, whereas T2 relaxation time values in the medial meniscus did not significantly change (p = 0.82). There was a significant association (p < 0.001) between cartilage T2 relaxation time values and age independent of weight and BMI, but no significant association between cartilage T2 relaxation time values and weight (p = 0.06) and BMI (p = 0.20) independent of age. CONCLUSION: Cartilage T2 relaxation time values significantly decreased in all cartilage subregions and meniscus T2 relaxation time values significantly increased in the lateral meniscus during maturation. These changes in T2 relaxation time values reflect age-related changes in tissue composition and microstructure.

Evaluation of Response to Enzalutamide Consecutively After Abiraterone Acetate/Prednisone Failure in Patients With Metastatic Castration-resistant Prostate Cancer.

INTRODUCTION: Treatment of metastatic castration-resistant prostate cancer (mCRPC) has evolved significantly during the past decade, and the preferred combination and/or sequence of these treatments remains controversial. In this retrospective study, we explored clinical and pathologic factors that could predict response to consecutive treatment with enzalutamide (ENZA) after disease progression (PD) on abiraterone acetate and prednisone (AA/P). PATIENTS AND METHODS: Data were collected from 40 consecutive patients with mCRPC who were treated with ENZA without other interim therapy after progression on AA/P. RESULTS: The median time from prostate cancer initial diagnosis to AA/P treatment was 6.2 (range, 0.9-16.3) years. The median prostate-specific antigen (PSA) progression-free survival (PSA-PFS) from treatment initiation was 8.5 months (95% confidence interval [CI], 7.1-10.1 months) and 2.3 months (95% CI, 1.8-3.4 months) on AA/P and ENZA, respectively. The median time to PD from treatment initiation was 9.7 months (95% CI, 7.1-12.4 months) and 3 months (95% CI, 2.3-4.1 months) on AA/P and ENZA, respectively. The correlations were weak between the best percent change in PSA on ENZA and time from diagnosis to AA/P initiation, best absolute or percentage change in PSA on AA/P, time to PSA progression or PD on AA/P. Patients with longer than the median duration of treatment with AA/P (11.73 months) had longer PSA-PFS on ENZA (median 2.8 vs. 1.9 months; P = .035). CONCLUSIONS: In this retrospective analysis, we did not find any clinical or pathologic factors associated with response to ENZA administered consecutively after AA/P. Patients with longer than median AA/P treatment duration had longer PSA-PFS on ENZA. Further evaluations and validation are greatly needed.

In pediatric familial hypercholesterolemia, lipoprotein(a) is more predictive than LDL-C for early onset of cardiovascular disease in family members.

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) level and lipoprotein(a) [Lp(a)] ≥ 50 mg/dL predict atherosclerotic cardiovascular disease (ASCVD) risk in adults with familial hypercholesterolemia (FH), but their role for children with FH is less clear. OBJECTIVE: This study examined the relationship between elevated Lp(a) and LDL-C levels in a pediatric population with FH and onset of ASCVD in family members. METHODS: Retrospective review of pediatric patients with FH identified LDL-C, Lp(a), and family history of ASCVD. Logistic regression modeling evaluated the association between the child's Lp(a) and peak LDL-C level with earliest age of ASCVD onset in their family. RESULTS: One hundred twenty-nine children from 109 families were identified. Children from families with early-onset ASCVD were 3 times more likely to have high Lp(a) than those with a family history of late-onset ASCVD (OR: 3.77, 95% CI: 1.16-12.25, P = .027) but were not more likely to have highly elevated peak LDL-C (≥190 mg/dL) (OR: 0.45, 95% CI: 0.11-1.80, P = .26). CONCLUSION: Children with FH and family history of early-onset ASCVD were more likely to have Lp(a) ≥50 mg/dL than children with FH and family history of late-onset ASCVD. Family history of early-onset ASCVD was more predictive of a child's Lp(a) level than of a child's peak LDL-C. Measurement of Lp(a) in children with FH may better characterize their cardiovascular risk, particularly when knowledge of family history is limited. Lp(a) testing may also identify children with FH that could benefit from more aggressive management to reduce ASCVD risk.

Do Headache Patients Require More Care in Between Visits Than Other Neurology Outpatients?

BACKGROUND: There is evidence that time spent in patient care in between patient visits is increasing and a contributor to physician burnout. The extent of this work on providers in the field of headache medicine is unknown. OBJECTIVES: To establish whether headache outpatients require a high level of care in addition to clinic visits, based on the quantity of remote encounters per patient (phone calls and secure email communication to the clinics), in comparison to other neurologic clinics. METHODS: In an academic referral clinic, a total of 3164 established patients were included in this retrospective analysis, 275 from the headache clinic, the remainder from various other neurology clinics (2 physician providers per clinic except 3 physician providers in the headache clinic). Patients presenting for a follow-up visit between January 2014 and April 2016 were observed for a 12-month period during which the number of a) telephone and b) secure email (MyChart) encounters per patient was recorded, and in addition, the number of entries related to each of these encounters. This analysis did not require IRB approval as per institutional guidelines. RESULTS: Headache clinic patients required a high frequency of remote encounters (composite of both telephone and email messages) per patient, second only to the MS clinic patients. Use of secure email messaging (MyChart) per patient was much higher in the headache clinic compared to all other clinics. CONCLUSION: Patients in a headache clinic in an academic tertiary care setting require a high intensity of remote outpatient care, more so than patients in other neurology subspecialty clinics and general neurology clinic, with the exception of the neuroimmunology/MS clinic. This is to a large extent secondary to the very frequent use of secure email linked to the electronic medical record by headache patients.

Utility of Genetic Testing in Addition to Mammography for Determining Risk of Breast Cancer Depends on Patient Age.

While screening and treatment have sharply reduced breast cancer mortality in the past 50 years, more targeted diagnostic testing may improve the accuracy and efficiency of care. Our retrospective, age-matched, case-control study evaluated the differential value of mammography and genetic variants to predict breast cancer depending on patient age. We developed predictive models using logistic regression with group lasso comparing (1) diagnostic mammography findings, (2) selected genetic variants, and (3) a combination of both. For women older than 60, mammography features were most predictive of breast cancer risk (imaging AUC = 0.74, genetic variants AUC = 0.54, combined AUC = 0.71). For women younger than 60 there is additional benefit to obtaining genetic testing (imaging AUC = 0.69, genetic variants AUC = 0.70, combined AUC = 0.72). In summary, genetic testing supplements mammography in younger women while mammography appears sufficient in older women for breast cancer risk prediction.