Citations

Objective The aim of this study was to quantitatively demonstrate radiation dose reduction for sinus and temporal bone examinations using high-resolution photon-counting detector (PCD) computed tomography (CT) with an additional tin (Sn) filter. Materials and Methods A multienergy CT phantom, an anthropomorphic head phantom, and a cadaver head were scanned on a research PCD-CT scanner using ultra-high-resolution mode at 100-kV tube potential with an additional tin filter (Sn-100 kV) and volume CT dose index of 10 mGy. They were also scanned on a commercial CT scanner with an energy-integrating detector (EID) following standard clinical protocols. Thirty patients referred to clinically indicated sinus examinations, and two patients referred to temporal bone examinations were scanned on the PCD-CT system after their clinical scans on an EID-CT. For the sinus cohort, PCD-CT scans were performed using Sn-100 kV at 4 dose levels at 10 mGy (n = 9), 8 mGy (n = 7), 7 mGy (n = 7), and 6 mGy (n = 7), and the clinical EID-CT was performed at 120 kV and 13.7 mGy (mean CT volume dose index). For the temporal bone scans, PCD-CT was performed using Sn-100 kV (10.1 mGy), and EID-CT was performed at 120 kV and routine clinical dose (52.6 and 66 mGy). For both PCD-CT and EID-CT, sinus images were reconstructed using H70 kernel at 0.75-mm slice thickness, and temporal bone images were reconstructed using a U70 kernel at 0.6-mm slice thickness. In addition, iterative reconstruction with a dedicated sharp kernel (V80) was used to obtain high-resolution PCD-CT images from a sinus patient scan to demonstrate improved anatomic delineation. Improvements in spatial resolution from the dedicated sharp kernel was quantified using modulation transfer function measured with a wire phantom. A neuroradiologist assessed the H70 sinus images for visualization of critical anatomical structures in low-dose PCD-CT images and routine-dose EID-CT images using a 5-point Likert scale (structural detection obscured and poor diagnostic confidence, score = 1; improved anatomic delineation and diagnostic confidence, score = 5). Image contrast and noise were measured in representative regions of interest and compared between PCD-CT and EID-CT, and the noise difference between the 2 acquisitions was used to estimate the dose reduction in the sinus and temporal bone patient cohorts. Results The multienergy phantom experiment showed a noise reduction of 26% in the Sn-100 kV PCD-CT image, corresponding to a total dose reduction of 56% compared with EID-CT (clinical dose) without compromising image contrast. The PCD-CT images from the head phantom and the cadaver scans demonstrated a dose reduction of 67% and 83%, for sinus and temporal bone examinations, respectively, compared with EID-CT. In the sinus cohort, PCD-CT demonstrated a mean dose reduction of 67%. The 10- and 8-mGy sinus patient images from PCD-CT were significantly superior to clinical EID-CT for visualization of critical sinus structures (median score = 5 ± 0.82 and P = 0.01 for lesser palatine foramina, median score = 4 ± 0.68 and P = 0.039 for nasomaxillary sutures, and median score = 4 ± 0.96 and P = 0.01 for anterior ethmoid artery canal). The 6- and 7-mGy sinus patient images did not show any significant difference between PCD-CT and EID-CT. In addition, V80 (sharp kernel, 10% modulation transfer function = 18.6 cm −1 ) PCD-CT images from a sinus patient scan increased the conspicuity of nasomaxillary sutures compared with the clinical EID-CT images. The temporal bone patient images demonstrated a dose reduction of up to 85% compared with clinical EID-CT images, whereas visualization of inner ear structures such as the incudomalleolar joint were similar between EID-CT and PCD-CT. Conclusions Phantom and cadaver studies demonstrated dose reduction using Sn-100 kV PCD-CT compared with current clinical EID-CT while maintaining the desired image contrast. Dose reduction was further validated in sinus and temporal bone patient studies. The ultra-high resolution capability from PCD-CT allowed improved anatomical delineation for sinus imaging compared with current clinical standard.

Abstract Delayed terminal duct lobular unit (TDLU) involution is associated with elevated mammographic breast density (MD). Both are independent breast cancer risk factors among women with benign breast disease (BBD). Prior digital analyses of normal breast tissues revealed that epithelial nuclear density (END) and TDLU involution are inversely correlated. Accordingly, we examined associations of END, TDLU involution, and MD in BBD clinical biopsies. This study included digitized images of 262 representative image-guided hematoxylin and eosin–stained biopsies from 224 women diagnosed with BBD, enrolled within the cross-sectional BREAST-Stamp project that were visually assessed for TDLU involution (TDLU count/100 mm2, median TDLU span and median acini count per TDLU). A digital algorithm estimated nuclei count per unit epithelial area, or END. Single X-ray absorptiometry of prebiopsy ipsilateral craniocaudal digital mammograms measured global and localized MD surrounding the biopsy region. Adjusted ordinal logistic regression models assessed relationships between tertiles of TDLU and END measures. Analysis of covariance examined mean differences in MD across END tertiles. TDLU measures were positively associated with increasing END tertiles [TDLU count/100 mm2, ORT3vsT1: 3.42, 95% confidence interval (CI), 1.87–6.28; acini count/TDLUT3vsT1, OR: 2.40, 95% CI, 1.39–4.15]. END was significantly associated with localized, but not, global MD. Relationships were most apparent among patients with nonproliferative BBD. These findings suggest that quantitative END reflects different but complementary information to the histologic information captured by visual TDLU and radiologic MD measures and merits continued evaluation in assessing cellularity of breast parenchyma to understand the etiology of BBD.

Abstract Background: Mammographic breast density (MBD) is a strong breast cancer (BC) risk factor, but its biologic underpinnings are poorly understood. Use of estrogen plus progestin menopausal hormone therapy is linked to increased MBD and BC risk. Experimental data suggest that ratios of tumor promoting (5α-dihydroprogesterone [5αP]) and anti-tumorigenic (3α-dihydroprogesterone [3αP]) progesterone metabolite levels may be related to BC risk. However, relationships of endogenous progesterone and its metabolites with MBD and BC risk have not been established. Accordingly, we assessed levels of circulating progesterone and its metabolites with MBD. Methods: In this cross-sectional study, serum progesterone and its metabolites were quantified using a novel liquid chromatography-tandem mass spectrometry assay in 103 postmenopausal and 52 premenopausal (luteal menstrual cycle phase) women, ages 40-65, undergoing diagnostic image-guided ipsilateral breast biopsy. MBD was measured as percent fibroglandular volume (MBD-V) on pre-biopsy digital mammograms using single X-ray absorptiometry. Square-root transformed MBD-V was examined across tertile categories of progesterone/progesterone metabolites using age and body mass index (BMI)-adjusted linear regression models. Results: Concentrations of the hormones were as follows among postmenopausal women: progesterone [mean: 12.6 pmol/L (range: 5.2-45.8)], 3αP [5.6 pmol/L (1.4-18.8)], 5αP [100 pmol/L (16.7-388)], and 5αP/3αP ratio [26.1 (2.1-150)]; and among luteal phase premenopausal women: progesterone [2063 pmol/L (13.6-7098), 3αP [12.7 pmol/L (2.4-64.4)], 5αP [243 pmol/L (25.3-774)], 5αP/3αP ratio [25.9 (2.3-73.7)]. Among postmenopausal women, progesterone was positively associated with MBD-V (Tertile 3 vs. 1: β=0.68, p-trend=0.02). A similar borderline positive association was observed among premenopausal women (β=0.74, p-trend=0.10). Additional adjustment for circulating estradiol did not substantively alter observed associations. Levels of 3αP, 5αP and the 5αP/3αP ratio were not associated with MBD-V among pre- or postmenopausal women. Conclusions: Concentrations of progesterone and it metabolites show substantial inter-woman variation. We observed a positive association between endogenous progesterone and MBD-V among both postmenopausal and premenopausal luteal phase women. We did not observe an association with the ratio of 5αP to 3αP levels and MBD-V. These findings suggest the need for additional studies to understand the biological basis of the role of progesterone and its metabolites in MBD and BC risk. Citation Format: Manila Hada, Hannah Oh, Sharon Fan, Roni T. Falk, Berta Geller, Pamela Vacek, Donald Weaver, John Shepherd, Jeff Wang, Bo Fan, Amir P. Mahmoudzadeh, Serghei Malkov, Sally Herschorn, Louise A. Brinton, Xia Xu, Mark E. Sherman, Britton Trabert, Gretchen L. Gierach. Relationship of serum progesterone and progesterone metabolites with mammographic density [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 588.

Objective To compare the risk of mortality and morbidity between outborn and propensity score-matched inborn extremely preterm neonates. Setting Multiple neonatal intensive care units (NICU) across the USA. Patients Singleton neonates born at 22–29 weeks’ gestation with no major anomalies who were admitted to a NICU and discharged between 2000 and 2014. Outborn neonates were restricted to those who transferred into a NICU on the day of birth. Methods The association between inborn-outborn status and the time-to-event outcomes of in-hospital mortality and necrotising enterocolitis (NEC) were assessed using Cox proportional hazards regression. Logistic regression was used to assess the remaining secondary outcomes: retinopathy of prematurity requiring treatment (tROP), chronic lung disease (CLD), periventricular leucomalacia (PVL) and severe intraventricular haemorrhage (IVH). Since outborn status was not random, we used 1:1 propensity score matching to reduce the imbalance in illness severity. Results There were 59 942 neonates (7991 outborn) included in the study. Outborn neonates had poorer survival than inborns and higher rates of NEC, severe IVH, tROP and PVL. Inborn-outborn disparities in mortality were reduced over the study period. When analysing the matched cohort (6524 matched pairs), outborns were less likely to die in-hospital compared with inborns (HR 0.84, 95% CI 0.77 to 0.91). However, outborns experienced higher rates of NEC (HR 1.14, 95% CI 1.04 to 1.25), severe IVH (OR 1.52, 95% CI 1.38 to 1.68), tROP (OR 1.45, 95% CI 1.25 to 1.69) and CLD (OR 1.12, 95% CI 1.01 to 1.24). Conclusion Additional research is needed to understand the contributors to increased morbidity for outborn extremely preterm neonates and identify interventions that mitigate this risk.

Background Despite a continued focus on improved cardiopulmonary resuscitation quality, survival remains low from in-hospital cardiac arrest. Advanced Resuscitation Training has been shown to improve survival to hospital discharge and survival with good neurological outcome following in-hospital cardiac arrest at its home institution. We sought to determine if Advanced Resuscitation Training implementation would improve patient outcomes and cardiopulmonary resuscitation quality at our institution. Methods This was a prospective, before–after study of adult in-hospital cardiac arrest victims who had cardiopulmonary resuscitation performed. During phase 1, standard institution cardiopulmonary resuscitation training was provided. During phase 2, providers received the same quantity of training, but with emphasis on Advanced Resuscitation Training principles. Primary outcomes were return of spontaneous circulation, survival to hospital discharge, and neurologically favorable survival. Secondary outcomes were cardiopulmonary resuscitation quality parameters. Results A total of 156 adult in-hospital cardiac arrests occurred during the study period. Rates of return of spontaneous circulation improved from 58.1 to 86.3% with an adjusted odds ratios of 5.31 (95% CI: 2.23–14.35, P < 0.001). Survival to discharge increased from 26.7 to 41.2%, adjusted odds ratios 2.17 (95% CI: 1.02–4.67, P < 0.05). Survival with a good neurological outcome increased from 24.8 to 35.3%, but was not statistically significant. Target chest compression rate increased from 30.4% of patients in P1 to 65.6% in P2, adjusted odds ratios 4.27 (95% CI: 1.72–11.12, P = 0.002), and target depth increased from 23.2% in P1 to 46.9% in P2, adjusted odds ratios 2.92 (95% CI: 1.16–7.54, P = 0.024). Conclusions After Advanced Resuscitation Training implementation, there were significant improvements in cardiopulmonary resuscitation quality and rates of return of spontaneous circulation and survival to discharge.

INTRODUCTION: Rates of long acting reversible contraception (LARC) use, including LNGIUS and LD-LNGIUS the United States are increasing. The aim of this study was to compare rates of and reasons for discontinuation of these two LARC. METHODS: Following IRB approval, premenopausal women 13-55 years old undergoing LD-LNGIUS (13.5 mg) insertion for contraception at Mayo Clinic Rochester from 1/1/2013 to 12/31/2015 were identified (n=82). A random sample of 328 women meeting the same criteria with LNGIUS insertion was identified. The cumulative incidence of discontinuation for symptom-related complaints was compared between groups after taking into account discontinuation for other reasons as a competing risk. RESULTS: Compared to those with LNGIUS, women with LD-LNGIUS were younger (mean age, 25.9 vs. 30.3 years), more likely to be nulliparous (86.6% vs. 28.0%), less likely to have previously used LARC (13.4% vs. 35.1%), and had lower BMI (mean, 25.2 vs. 27.0 kg/m 2 ). In women with subsequent follow-up, 57.3% (43/75) of the women with LD-LNGIUS expressed a symptom concern compared to 60.9% (171/281) of the women with LNGIUS. The cumulative incidence of discontinuation for symptom-related complaints by 2 years was higher in the LD-LNGIUS group, with rates of 20.0% vs. 13.8% based on patients with follow-up and 23.4% vs.12.8% based on a subset of 58+58 women matched on age, race, gravidity, and insertion year. CONCLUSION: Women with LD-LNGIUS are less likely to express symptom concerns than women with LNGIUS, but more likely to discontinue for symptom-related complaints. These findings may inform counseling of women with hormonal intrauterine contraception placement.

INTRODUCTION: To compare two published risk stratification criteria (Milwaukee Model vs. Mayo Criteria) to predict lymphatic dissemination (LD) in endometrioid endometrial cancer (EC). METHODS: Patients who underwent surgery for EC between 1/1/2004-9/30/2013 and had endometrioid histology without stage IV disease were included and classified as either low-risk or at-risk for LD using two independent risk stratification systems. LD was defined as positive nodes at time of surgery or lymph node recurrence within 2 years of surgery after negative lymph node assessment (LNA) or when LNA was not performed. False positive (FP) and false negative (FN) rates for each risk model were calculated. RESULTS: Among 1103 patients, 81 (7.3%) had LD (72 positive LN and 9 LN recurrences). Most patients (90.2%) had stage I disease. Integration of the Milwaukee Model was associated with a low at-risk rate for LD (38.1%) but a relatively high FN rate (13.6%, 95% CI 7.0-23.0). Conversely, the traditional Mayo Criteria using a tumor diameter (TD) cutoff of ≤2 cm (vs >2 cm) had a higher at-risk rate for LD (69.5%) but a FN rate of 0.0% (95% CI, 0-4.5). Modifying Mayo Criteria using a TD cutoff of ≤3 cm (vs >3 cm) identified fewer women at-risk than using ≤2 cm cutoff (56.8% vs. 69.5%), but had a higher FN rate of 3.7% (95% CI, 0.8-10.4). CONCLUSIONS: The Milwaukee Model had the lowest at-risk rate of LD but an unacceptable FN rate. Modifying the Mayo Criteria by increasing the TD cutoff from the traditional ≤2 cm to ≤3 cm would spare an estimated 12.7% of patients LNA, but the accompanying FN rate is unacceptably high. The traditional Mayo Criteria for low-risk EC remains the most accurate in determining which patients LNA can be omitted.