The risk of recurrent small-for-gestational-age infants at term is dependent on the number of previously affected births.

BACKGROUND: Small-for-gestational-age infants are at a substantially increased risk of perinatal complications, but the risk of recurrent small-for-gestational-age is not well known, particularly because there are many demographic and obstetrical factors that interact and modify this risk. We investigated the relationship between previous small-for-gestational-age births and the risk of recurrence at term in a large Australian cohort. OBJECTIVE: We aimed to identify key demographic and obstetrical variables that influence the risk of recurrence of a small-for-gestational-age infant at term. The primary outcome measure was the odds of recurrence of small-for-gestational-age in subsequent pregnancies up to a maximum of 4 consecutive term births. STUDY DESIGN: This was a retrospective analysis of women who had more than 1 consecutive nonanomalous, singleton, term live births between July 1997 and September 2018 at the Mater Mother's Hospital in Brisbane, Australia. Women with multiple pregnancy, preterm birth, or major congenital malformations were excluded. Small-for-gestational-age was defined as birthweight at the <10th centile. We calculated the odds of recurrence depending on the number of previous small-for-gestational-age infants and if only the preceding infant was small-for-gestational-age. The study population was dichotomized into small-for-gestational-age and non-small-for-gestational-age for each consecutive pregnancy. Univariate analyses compared baseline demographic and obstetrical characteristics followed by logistic regression modeling to determine the odds of recurrence in the second, third, and fourth pregnancies. RESULTS: The final study comprised 24,819 women. The proportion of women who had a small-for-gestational-age infant in their first pregnancy was 9.4%, whereas the proportion of women who had a small-for-gestational-age infant in their second, third, and fourth pregnancies after the birth of a previous small-for-gestational-age infant were 20.5% (479 of 2338), 24.6% (63 of 256), and 30.4% (14 of 46), respectively. Regardless of parity, the odds of recurrence increased if the preceding infant was small-for-gestational-age. The odds of recurrence increased markedly if there was more than 1 previous small-for-gestational-age infant. In women with 3 previous small-for-gestational-age infants, the adjusted odds of another small-for-gestational-age infant were 66.00 (95% confidence interval, 11.35-383.76). Maternal age, body mass index, ethnicity, and smoking were significant risk factors for recurrent small-for-gestational-age. However, maternal diabetes mellitus or hypertension, either in a previous or current pregnancy, did not influence the risk of recurrence. CONCLUSION: The risk of recurrence in a subsequent pregnancy increased if there was a previous small-for-gestational-age birth. Women with consecutive small-for-gestational-age infants were at the highest risk of recurrence. Our results highlight that women with a previous small-for-gestational-age infant are at a substantial risk of another small infant and need to be counseled and monitored appropriately.

NHLBI-Sponsored Randomized Trial of Postconditioning During Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction.

RATIONALE: Postconditioning at the time of primary percutaneous coronary intervention (PCI) for ST-segment-elevation myocardial infarction may reduce infarct size and improve myocardial salvage. However, clinical trials have shown inconsistent benefit. OBJECTIVE: We performed the first National Heart, Lung, and Blood Institute-sponsored trial of postconditioning in the United States using strict enrollment criteria to optimize the early benefits of postconditioning and assess its long-term effects on left ventricular (LV) function. METHODS AND RESULTS: We randomized 122 ST-segment-elevation myocardial infarction patients to postconditioning (4, 30 seconds PTCA [percutaneous transluminal coronary angioplasty] inflations/deflations)+PCI (n=65) versus routine PCI (n=57). All subjects had an occluded major epicardial artery (thrombolysis in myocardial infarction=0) with ischemic times between 1 and 6 hours with no evidence of preinfarction angina or collateral blood flow. Cardiac magnetic resonance imaging measured at 2 days post-PCI showed no difference between the postconditioning group and control in regards to infarct size (22.5±14.5 versus 24.0±18.5 g), myocardial salvage index (30.3±15.6% versus 31.5±23.6%), or mean LV ejection fraction. Magnetic resonance imaging at 12 months showed a significant recovery of LV ejection fraction in both groups (61.0±11.4% and 61.4±9.1%; P<0.01). Subjects randomized to postconditioning experienced more favorable remodeling over 1 year (LV end-diastolic volume =157±34 to 150±38 mL) compared with the control group (157±40 to 165±45 mL; P<0.03) and reduced microvascular obstruction ( P=0.05) on baseline magnetic resonance imaging and significantly less adverse LV remodeling compared with control subjects with microvascular obstruction ( P<0.05). No significant adverse events were associated with the postconditioning protocol and all patients but one (hemorrhagic stroke) survived through 1 year of follow-up. CONCLUSIONS: We found no early benefit of postconditioning on infarct size, myocardial salvage index, and LV function compared with routine PCI. However, postconditioning was associated with improved LV remodeling at 1 year of follow-up, especially in subjects with microvascular obstruction. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01324453.

Lessons Learned from Applying a Modified Learning Collaborative Model to Promote Change in Regional and Statewide HIV Care Systems.

The Health Resources and Services Administration Special Projects of National Significance launched the Systems Linkage and Access to Care for Populations at High Risk of HIV Infection Initiative in 2011. Six state departments of health were funded to utilize a modified Learning Collaborative model to develop and/or adapt HIV testing, linkage to care and retention in care system-level interventions. More than 60 Learning Sessions were held over the course of the Learning Collaborative. A total of 22 unique interventions were tested with 18 interventions selected and scaled up. All interventions were created to impact services at a systems level, with standardized protocols developed to ensure fidelity. Our findings provide key lessons and present considerations for replication for use of a modified Learning Collaborative to achieve state-level systems change.

Advantages of breast cancer visualization and characterization using synchrotron radiation phase-contrast tomography.

The aim of this study was to highlight the advantages that propagation-based phase-contrast computed tomography (PB-CT) with synchrotron radiation can provide in breast cancer diagnostics. For the first time, a fresh and intact mastectomy sample from a 60 year old patient was scanned on the IMBL beamline at the Australian Synchrotron in PB-CT mode and reconstructed. The clinical picture was described and characterized by an experienced breast radiologist, who underlined the advantages of providing diagnosis on a PB-CT volume rather than conventional two-dimensional modalities. Subsequently, the image quality was assessed by 11 breast radiologists and medical imaging experts using a radiological scoring system. The results indicate that, with the radiation dose delivered to the sample being equal, the accuracy of a diagnosis made on PB-CT images is significantly higher than one using conventional techniques.

Mobile Multidisciplinary HIV Medical Care for Hard-to-Reach Individuals Experiencing Homelessness in San Francisco.

The San Francisco, California-based HIV Homeless-Health Outreach Mobile Engagement (HHOME) program aims to improve health and housing outcomes for multiply diagnosed people experiencing chronic homelessness whom the HIV care system has failed to reach. From 2014 to 2017, HHOME's mobile multidisciplinary team served 106 clients. Viral suppression increased from 23.6% to 60%, and 73.8% obtained permanent supportive housing (n = 61). System-level changes included the adoption of city-wide standardized acuity assessment tools HIV Care Coordination Taskforce by community partners. This article highlights HHOME's core components and its public health implications.

Peer Support and the HIV Continuum of Care: Results from a Multi-Site Randomized Clinical Trial in Three Urban Clinics in the United States.

Racial/ethnic minorities living with HIV and behavioral health co-morbidities are more likely to be disengaged from HIV primary care. Peer programs have been effective in HIV outreach and prevention but effectiveness of such programs for retention in care and viral suppression is understudied. Subjects (n = 348) were randomized in equal allocation to a peer navigation and education intervention versus standard clinical care at three urban clinics in the United States. The intervention group received seven structured interventions plus weekly contact to address medical and social needs. Primary outcomes included time-to-first 4-month gap in HIV care and viral suppression up to 12 months of follow-up. Intention-to-treat analysis showed no difference between groups on 4-month gap in HIV primary care, but subgroup analysis showed a suggestive effect of the peer intervention in reducing gaps in care among stably housed subjects. Fully compliant subjects in the peer intervention experienced significantly fewer 4-month gaps in HIV primary care (p < 0.0001). Those in the peer group who had more clinical face-to-face encounters in the first 3 months were also significantly more likely to have better retention in care (p = 0.04). There were no significant differences between any study subgroups in viral suppression at 12 months. Peer interventions may improve retention in primary care among subgroups of people living with HIV from racial/ethnic minority communities, although such improved retention may not increase viral load suppression. Attending and completing structured educational sessions along with early, intensive contact with peers could improve retention in HIV primary care for patients. Future peer programs should consider training on housing referral systems to help increase retention for patients who are not stably housed. clinicaltrials.gov registration number: NCT01616940.

Changes in aldehyde dehydrogenase-1 expression during neoadjuvant chemotherapy predict outcome in locally advanced breast cancer.

INTRODUCTION: Although neoadjuvant chemotherapy (NAC) for locally advanced breast cancer can improve operability and local disease control, there is a lack of reliable biomarkers that predict response to chemotherapy or long-term survival. Since expression of aldehyde dehydrogenase-1 (ALDH1) is associated with the stem-like properties of self-renewal and innate chemoresistance in breast cancer, we asked whether expression in serial tumor samples treated with NAC could identify women more likely to benefit from this therapy. METHODS: Women with locally advanced breast cancer were randomly assigned to receive four cycles of anthracycline-based chemotherapy, followed by four cycles of taxane therapy (Arm A), or the same regimen in reverse order (Arm B). Tumor specimens were collected at baseline, after four cycles, and then at surgical resection. ALDH1 expression was determined by immunohistochemistry and correlated with tumor response using Fisher's exact test while Kaplan-Meier method was used to calculate survival. RESULTS: A hundred and nineteen women were enrolled into the study. Fifty seven (48%) were randomized to Arm A and 62 (52%) to Arm B. Most of the women (90%) had ductal carcinoma and 10% had lobular carcinoma. Of these, 26 (22%) achieved a pathological complete response (pCR) after NAC. There was no correlation between baseline ALDH1 expression and tumor grade, stage, hormone receptor, human epidermal growth factor receptor 2 (HER2) status and Ki67 index. ALDH1 negativity at baseline was significantly associated with pCR (P = 0.004). The presence of ALDH1(+) cells in the residual tumor cells in non-responding women was strongly predictive of worse overall survival (P = 0.024). Moreover, serial analysis of specimens from non-responders showed a marked increase in tumor-specific ALDH1 expression (P = 0.028). Overall, there was no survival difference according to the chemotherapy sequence. However, poorly responding tumours from women receiving docetaxel chemotherapy showed an unexpected significant increase in ALDH1 expression. CONCLUSIONS: ALDH1 expression is a useful predictor of chemoresistance. The up-regulation of ALDH1 after NAC predicts poor survival in locally advanced breast cancer. Although the chemotherapy sequence had no effect on overall prognosis, our results suggest that anthracycline-based chemotherapy may be more effective at targeting ALDH1(+) breast cancer cells. TRIAL REGISTRATION: ACTRN12605000588695.

IL-33 is more potent than IL-25 in provoking IL-13-producing nuocytes (type 2 innate lymphoid cells) and airway contraction.

BACKGROUND: IL-25 and IL-33 belong to distinct cytokine families, but experimental mouse studies suggest their immunologic functions in type 2 immunity are almost entirely overlapping. However, only polymorphisms in the IL-33 pathway (IL1RL1 and IL33) have been significantly associated with asthma in large-cohort genome-wide association studies. OBJECTIVE: We sought to identify distinct pathways for IL-25 and IL-33 in the lung that might provide insight into their roles in asthma pathogenesis and potential for therapeutic intervention. METHODS: IL-25 receptor-deficient (Il17rb(-/-)), IL-33 receptor-deficient (ST2, Il1rl1(-/-)), and double-deficient (Il17rb(-/-)Il1rl1(-/-)) mice were analyzed in models of allergic asthma. Microarrays, an ex vivo lung slice airway contraction model, and Il13(+/eGFP) mice were then used to identify specific effects of IL-25 and IL-33 administration. RESULTS: Comparison of IL-25 and IL-33 pathway-deficient mice demonstrates that IL-33 signaling plays a more important in vivo role in airways hyperreactivity than IL-25. Furthermore, methacholine-induced airway contraction ex vivo increases after treatment with IL-33 but not IL-25. This is dependent on expression of the IL-33 receptor and type 2 cytokines. Confocal studies with Il13(+/eGFP) mice show that IL-33 more potently induces expansion of IL-13-producing type 2 innate lymphoid cells, correlating with airway contraction. This predominance of IL-33 activity is enforced in vivo because IL-33 is more rapidly expressed and released in comparison with IL-25. CONCLUSION: Our data demonstrate that IL-33 plays a critical role in the rapid induction of airway contraction by stimulating the prompt expansion of IL-13-producing type 2 innate lymphoid cells, whereas IL-25-induced responses are slower and less potent.

Developing evaluation measures for health departments sharing and linking HIV and STI surveillance data.

Enhancing data sharing, quality, and use across siloed HIV and STI programs is critical for national and global initiatives to reduce new HIV infections and improve the health of people with HIV. As part of the Enhancing Linkage of STI and HIV Surveillance Data in the Ryan White HIV/AIDS Program initiative, four health departments (HDs) in the U.S. received technical assistance to better share and link their HIV and STI surveillance data. The process used to develop evaluation measures assessing implementation and outcomes of linking HIV and STI data systems involved six steps: 1) measure selection and development, 2) review and refinement, 3) testing, 4) implementation and data collection, 5) data quality review and feedback, and 6) dissemination. Findings from pilot testing warranted slight adaptations, including starting with a core set of measures and progressively scaling up. Early findings showed improvements in data quality over time. Lessons learned included identifying and engaging key stakeholders early; developing resources to assist HDs; and considering measure development as iterative processes requiring periodic review and reassessment to ensure continued utility. These findings can guide programs and evaluations, especially those linking data across multiple systems, in developing measures to track implementation and outcomes over time.

Surgical management of breast cancer in Victoria: A state-wide audit.

AIM: The Victorian Tumour Summits are an initiative of the Victorian Integrated Cancer Services to engage clinicians and consumers in identifying unwarranted variations in cancer care across the state. From the analysis presented at the Victorian Breast Tumour Summit in 2021, this study provides a state-wide overview of epidemiology and surgical care of breast cancer in Victoria to outline any variations in care across the state, and limitations in data reporting, which impacts the understanding of breast cancer burden and service planning. METHODS: A retrospective analysis of Victorian breast cancer patients diagnosed between 2016 and 2018 was performed using a linked data set provided by the Department of Health. The linked data sources include Victorian Cancer Registry, Victorian Admitted Episodes Dataset and Victorian Radiotherapy Minimum Data Set, from which patient demographic details, tumor characteristics and treatment records were extracted. Pearson's chi-squared test was used to determine the statistical significance of relationships between various categorical parameters. Variables including demographics, types of surgery (breast-conserving vs. mastectomy), rates of neoadjuvant chemotherapy, and time to surgery were examined. RESULTS: One thousand nine hundred thirty-seven patients with ductal carcinoma in situ and 13,375 patients with invasive breast cancer (IBC) were included. Of 11,351 patients with stages I-III IBC (85%, N = 13,375) 66% underwent breast-conserving surgery (BCS), and 31% underwent mastectomy. The ratio of mastectomy to BCS increased with increasing disease stage. Neoadjuvant chemotherapy was utilized in 11% of early IBC patients who were surgically treated. Eighty-three percent of patients undergoing upfront breast surgery were treated within 5 weeks of diagnosis, with a significant difference in the median time to surgery between public and private sectors. Breast reconstruction was performed in 37% of mastectomy patients, of whom 83% underwent immediate breast reconstruction, and 17% underwent delayed breast reconstruction. CONCLUSIONS: Victorian breast cancer data show a high quality of surgical care coordination. Significant gaps in our data warrant future improvements in the Victorian breast cancer notification system and access to pharmaceutical data for an enhanced understanding of the breast cancer treatment pathways and care delivery.

Propagation-based phase-contrast imaging of the breast: image quality and the effect of X-ray energy and radiation dose.

OBJECTIVES: Propagation-based phase-contrast computed tomography (PB-CT) is a new imaging technique that exploits refractive and absorption properties of X-rays to enhance soft tissue contrast and improve image quality. This study compares image quality of PB-CT and absorption-based CT (AB-CT) for breast imaging while exploring X-ray energy and radiation dose. METHODS: Thirty-nine mastectomy samples were scanned at energy levels of 28-34keV using a flat panel detector at radiation dose levels of 4mGy and 2mGy. Image quality was assessed using signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), spatial resolution (res) and visibility (vis). Statistical analysis was performed to compare PB-CT images against their corresponding AB-CT images scanned at 32keV and 4mGy. RESULTS: The PB-CT images at 4mGy, across nearly all energy levels, demonstrated superior image quality than AB-CT images at the same dose. At some energy levels, the 2mGy PB-CT images also showed better image quality in terms of CNR/Res and vis compared to the 4mGy AB-CT images. At both investigated doses, SNR and SNR/res were found to have a statistically significant difference across all energy levels. The difference in vis was statistically significant at some energy levels. CONCLUSION: This study demonstrates superior image quality of PB-CT over AB-CT, with X-ray energy playing a crucial role in determining image quality parameters. ADVANCES IN KNOWLEDGE: Our findings reveal that standard dose PB-CT outperforms standard dose AB-CT across all image quality metrics. Additionally, we demonstrate that low dose PB-CT can produce superior images compared to standard dose AB-CT in terms of CNR/Res and vis.

Recognition of the major cat allergen Fel d 1 through the cysteine-rich domain of the mannose receptor determines its allergenicity.

Dendritic cells are professional antigen-presenting cells that are specialized in antigen uptake and presentation. Allergy to cat has increased substantially in recent years and has been shown to be positively associated with asthma. We have recently shown that the mannose receptor (MR), a C-type lectin expressed by dendritic cells, recognizes various glycoallergens from diverse sources and is involved in promoting allergic responses to a major house dust mite allergen in vitro. Here we investigated the potential role of MR in allergic responses to Fel d 1, a major cat allergen. Fel d 1 binding to MR was confirmed by ELISA. Using blocking, gene silencing (siRNA) experiments, and MR knock-out (MR(-/-)) cells, we have demonstrated that MR plays a major role in internalization of Fel d 1 by human and mouse antigen-presenting cells. Intriguingly, unlike other glycoallergens, recognition of Fel d 1 by MR is mediated by the cysteine-rich domain, which correlates with the presence of sulfated carbohydrates in natural Fel d 1. WT and MR(-/-) mice were used to study the role of MR in allergic sensitization to Fel d 1 in vivo. MR(-/-) mice sensitized with cat dander extract and Fel d 1 produced significantly lower levels of total IgE, Fel d 1-specific-IgE and IgG1, the hallmarks of allergic response, compared with WT mice. Our data show for the first time that Fel d 1 is a novel ligand of the cysteine-rich domain of MR and that MR is likely to play a pivotal role in allergic sensitization to airborne allergens in vivo.

Occurrence and impact of pelvic floor dysfunction in women with and without breast cancer: a cross-sectional study.

BACKGROUND: One of the sequalae of breast cancer treatments may be pelvic floor (PF) dysfunction such as urinary incontinence (UI), faecal incontinence (FI), and pelvic organ prolapse (POP). OBJECTIVE: The aim of this study was to compare the occurrence and related distress and impact of PF dysfunction between women with and without breast cancer. METHODS: Women with and without breast cancer participated in this cross-sectional study. The Pelvic Floor Distress Inventory and Pelvic Floor Impact Questionnaire were used to quantify the prevalence and related distress, and impact of PF dysfunction. Factors associated with PF outcomes were examined using logistic and linear regressions while controlling for known risk factors for PF dysfunction (age, body mass index, and parity). RESULTS: 120 women with breast cancer, and 170 women without breast cancer responded. The occurrence of any type of UI was higher in women with breast cancer than women without breast cancer (percentage difference=17%; 95% CI: 7, 29). Women with breast cancer experienced higher impact of urinary symptoms (mean difference=18.2; 95% CI: 8.9, 27.7) compared to those without. Multivariable analysis indicated that having breast cancer (ß 0.33; 95%CI: 0.08, 0.51) was the strongest predictor of greater impact of urinary symptoms. CONCLUSION: Women with breast cancer reported a higher occurrence and impact of urinary symptoms than women without breast cancer. While further studies are required to confirm our findings, routine screening and offering treatment for urinary symptoms may be indicated for women with breast cancer.

A typology of models for expanding access to oral health care for people living with HIV/AIDS.

OBJECTIVES: This article describes a typology of program models for expanding access to dental services for people living with HIV/AIDS (PLWHA). These programs serve communities with limited access and high unmet need for oral health care, such as rural areas, low-income and racial/ethnic minorities. METHODS: Interviews and site visits with dental and program directors were conducted at participating sites, including AIDS service organizations, community health centers, and university-affiliated medical centers or hospitals. RESULTS: Despite the differences across organizational structure, similar models and approaches were developed to engage and retain PLWHA in dental care. These approaches included: using mobile dental units; expanding the type and availability of previous dental services provided; providing training opportunities for dental residents and hygienists; establishing linkages with medical providers; providing transportation and other ancillary services; using dental case managers and peer navigators to coordinate care; and patient education. CONCLUSIONS: This typology can assist program planners, medical and dental care providers with service delivery strategies for addressing the unmet need for oral health care in their area.

Stress and depression among Latina women in rural southeastern North Carolina.

The purposes of this study were to assess the level of depression and types of major stressors, and to identify stressors contributing to depression, among 135 Latina women in rural southeastern North Carolina. Nearly half of the participants (47.6%) had scores of greater than, or equal to, 16 on the Center for Epidemiologic Studies Depression Scale, used to identify possible depression, suggesting the need for early intervention. "Difficult to be away from family members," "immigration status," and "religion" were the most reliable predictors of stress, accounting for 34.5% of the total variance in depression.

Factors Associated with Increased Risk of Early Severe Neonatal Morbidity in Late Preterm and Early Term Infants.

Although the risk of neonatal mortality is generally low for late preterm and early term infants, they are still significantly predisposed to severe neonatal morbidity (SNM) despite being born at relatively advanced gestations. In this study, we investigated maternal and intrapartum risk factors for early SNM in late preterm and early term infants. This was a retrospective cohort study of non-anomalous, singleton infants (34+0-38+6 gestational weeks) born at the Mater Mother's Hospital in Brisbane, Australia from January 2015 to May 2020. Early SNM was defined as a composite of any of the following severe neonatal outcome indicators: admission to neonatal intensive care unit (NICU) in conjunction with an Apgar score <4 at 5 min, severe respiratory distress, severe neonatal acidosis (cord pH < 7.0 or base excess <-12 mmol/L). Multivariable binomial logistic regression analyses using generalized estimating equations (GEE) were used to identify risk factors. Of the total infants born at 34+0-38+6 gestational weeks, 5.7% had at least one component of the composite outcome. For late preterm infants, pre-existing diabetes mellitus, instrumental birth and emergency caesarean birth for non-reassuring fetal status were associated with increased odds for early SNM, whilst for early term infants, pre-existing and gestational diabetes mellitus, antepartum hemorrhage, instrumental, emergency caesarean and elective caesarean birth were significant risk factors. In conclusion, we identified several risk factors contributing to early SNM in late preterm and early term cohort. Our results suggest that predicted probability of early SNM decreased as gestation increased.

Factors involved in treatment decision making for women diagnosed with ductal carcinoma in situ: A qualitative study.

Whilst some of the diversity in management of women with ductal carcinoma in situ (DCIS) may be explained by tumour characteristics, the role of patient preference and the factors underlying those preferences have been less frequently examined. We have used a descriptive qualitative study to explore treatment decisions for a group of Australian women diagnosed with DCIS through mammographic screening. Semi-structured telephone interviews were performed with 16 women diagnosed with DCIS between January 2012 and December 2018, recruited through the LifePool dataset (a subset of BreastScreen participants who have agreed to participate in research). Content analysis using deductive coding identified three themes: participants did not have a clear understanding of their diagnosis or prognosis; reported involvement in decision making about management varied; specific factors including the psychosexual impact of mastectomy and perceptions of radiotherapy, could act as barriers or facilitators to specific decisions about treatment. The treatment the women received was not simply determined by the characteristics of their disease. Interaction with the managing clinician was pivotal, however many other factors played a part in individual decisions. Recognising that decisions are not purely a function of disease characteristics is important for both women with DCIS and the clinicians who care for them.

Propagation-Based Phase-Contrast CT of the Breast Demonstrates Higher Quality Than Conventional Absorption-Based CT Even at Lower Radiation Dose.

RATIONALE AND OBJECTIVES: Propagation-based phase-contrast CT (PB-CT) is an advanced X-ray imaging technology that exploits both refraction and absorption of the transmitted X-ray beam. This study was aimed at optimizing the experimental conditions of PB-CT for breast cancer imaging and examined its performance relative to conventional absorption-based CT (AB-CT) in terms of image quality and radiation dose. MATERIALS AND METHODS: Surgically excised breast mastectomy specimens (n = 12) were scanned using both PB-CT and AB-CT techniques under varying imaging conditions. To evaluate the radiological image quality, visual grading characteristics (VGC) analysis was used in which 11 breast specialist radiologists compared the overall image quality of PB-CT images with respect to the corresponding AB-CT images. The area under the VGC curve was calculated to measure the differences between PB-CT and AB-CT images. RESULTS: The highest radiological quality was obtained for PB-CT images using a 32 keV energy X-ray beam and by applying the Homogeneous Transport of Intensity Equation phase retrieval with the value of its parameter γ set to one-half of the theoretically optimal value for the given materials. Using these optimized conditions, the image quality of PB-CT images obtained at 4 mGy and 2 mGy mean glandular dose was significantly higher than AB-CT images at 4 mGy (AUCVGC = 0.901, p = 0.001 and AUCVGC = 0.819, p = 0.011, respectively). CONCLUSION: PB-CT achieves a higher radiological image quality compared to AB-CT even at a considerably lower mean glandular dose. Successful translation of the PB-CT technique for breast cancer imaging can potentially result in improved breast cancer diagnosis.

Effect of x-ray energy on the radiological image quality in propagation-based phase-contrast computed tomography of the breast.

Purpose: Breast cancer is the most common cancer in women in developing and developed countries and is responsible for 15% of women's cancer deaths worldwide. Conventional absorption-based breast imaging techniques lack sufficient contrast for comprehensive diagnosis. Propagation-based phase-contrast computed tomography (PB-CT) is a developing technique that exploits a more contrast-sensitive property of x-rays: x-ray refraction. X-ray absorption, refraction, and contrast-to-noise in the corresponding images depend on the x-ray energy used, for the same/fixed radiation dose. The aim of this paper is to explore the relationship between x-ray energy and radiological image quality in PB-CT imaging. Approach: Thirty-nine mastectomy samples were scanned at the imaging and medical beamline at the Australian Synchrotron. Samples were scanned at various x-ray energies of 26, 28, 30, 32, 34, and 60 keV using a Hamamatsu Flat Panel detector at the same object-to-detector distance of 6 m and mean glandular dose of 4 mGy. A total of 132 image sets were produced for analysis. Seven observers rated PB-CT images against absorption-based CT (AB-CT) images of the same samples on a five-point scale. A visual grading characteristics (VGC) study was used to determine the difference in image quality. Results: PB-CT images produced at 28, 30, 32, and 34 keV x-ray energies demonstrated statistically significant higher image quality than reference AB-CT images. The optimum x-ray energy, 30 keV, displayed the largest area under the curve ( AUC VGC ) of 0.754 ( p = 0.009 ). This was followed by 32 keV ( AUC VGC = 0.731 , p ≤ 0.001 ), 34 keV ( AUC VGC = 0.723 , p ≤ 0.001 ), and 28 keV ( AUC VGC = 0.654 , p = 0.015 ). Conclusions: An optimum energy range (around 30 keV) in the PB-CT technique allows for higher image quality at a dose comparable to conventional mammographic techniques. This results in improved radiological image quality compared with conventional techniques, which may ultimately lead to higher diagnostic efficacy and a reduction in breast cancer mortalities.

The role of chemotherapeutic drugs in the evaluation of breast tumour response to chemotherapy using serial FDG-PET.

INTRODUCTION: The aims of this study were to investigate whether drug sequence (docetaxel followed by anthracyclines or the drugs in reverse order) affects changes in the maximal standard uptake volume (SUVmax) on [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) during neoadjuvant chemotherapy in women with locally advanced breast cancer. METHODS: Women were randomly assigned to receive either drug sequence, and FDG-PET scans were taken at baseline, after four cycles and after eight cycles of chemotherapy. Tumour response to chemotherapy was evaluated based on histology from a surgical specimen collected upon completion of chemotherapy. RESULTS: Sixty women were enrolled into the study. Thirty-one received docetaxel followed by anthracyclines (Arm A) and 29 received drugs in the reverse order (Arm B). Most women (83%) had ductal carcinoma and 10 women (17%) had lobular or lobular/ductal carcinoma. All but one tumour were downstaged during therapy. Overall, there was no significant difference in response between the two drug regimens. However, women in Arm B who achieved complete pathological response had mean FDG-PET SUVmax reduction of 87.7% after four cycles, in contrast to those who had no or minor pathological response. These women recorded mean SUVmax reductions of only 27% (P < 0.01). Women in Arm A showed no significant difference in SUVmax response according to pathological response. Sensitivity, specificity, accuracy and positive and negative predictive values were highest in women in Arm B. CONCLUSIONS: Our results show that SUVmax uptake by breast tumours during chemotherapy can be dependent on the drugs used. Care must be taken when interpreting FDG-PET in settings where patients receive varied drug protocols.