Advanced risk prediction for aortic dissection patients using imaging-based computational flow analysis.

Patients with either a repaired or medically managed aortic dissection have varying degrees of risk of developing late complications. High-risk patients would benefit from earlier intervention to improve their long-term survival. Currently serial imaging is used for risk stratification, which is not always reliable. On the other hand, understanding aortic haemodynamics within a dissection is essential to fully evaluate the disease and predict how it may progress. In recent decades, computational fluid dynamics (CFD) has been extensively applied to simulate complex haemodynamics within aortic diseases, and more recently, four-dimensional (4D)-flow magnetic resonance imaging (MRI) techniques have been developed for in vivo haemodynamic measurement. This paper presents a comprehensive review on the application of image-based CFD simulations and 4D-flow MRI analysis for risk prediction in aortic dissection. The key steps involved in patient-specific CFD analyses are demonstrated. Finally, we propose a workflow incorporating computational modelling for personalised assessment to aid in risk stratification and treatment decision-making.

Preventing ovariectomy-induced weight gain decreases tumor burden in rodent models of obesity and postmenopausal breast cancer.

BACKGROUND: Obesity and adult weight gain are linked to increased breast cancer risk and poorer clinical outcomes in postmenopausal women, particularly for hormone-dependent tumors. Menopause is a time when significant weight gain occurs in many women, and clinical and preclinical studies have identified menopause (or ovariectomy) as a period of vulnerability for breast cancer development and promotion. METHODS: We hypothesized that preventing weight gain after ovariectomy (OVX) may be sufficient to prevent the formation of new tumors and decrease growth of existing mammary tumors. We tested this hypothesis in a rat model of obesity and carcinogen-induced postmenopausal mammary cancer and validated our findings in a murine xenograft model with implanted human tumors. RESULTS: In both models, preventing weight gain after OVX significantly decreased obesity-associated tumor development and growth. Importantly, we did not induce weight loss in these animals, but simply prevented weight gain. In both lean and obese rats, preventing weight gain reduced visceral fat accumulation and associated insulin resistance. Similarly, the intervention decreased circulating tumor-promoting growth factors and inflammatory cytokines (i.e., BDNF, TNFα, FGF-2), with greater effects in obese compared to lean rats. In obese rats, preventing weight gain decreased adipocyte size, adipose tissue macrophage infiltration, reduced expression of the tumor-promoting growth factor FGF-1 in mammary adipose, and reduced phosphorylated FGFR indicating reduced FGF signaling in tumors. CONCLUSIONS: Together, these findings suggest that the underlying mechanisms associated with the anti-tumor effects of weight maintenance are multi-factorial, and that weight maintenance during the peri-/postmenopausal period may be a viable strategy for reducing obesity-associated breast cancer risk and progression in women.

Investigation of the safety and feasibility of AAV1/SERCA2a gene transfer in patients with chronic heart failure supported with a left ventricular assist device - the SERCA-LVAD TRIAL.

The SERCA-LVAD trial was a phase 2a trial assessing the safety and feasibility of delivering an adeno-associated vector 1 carrying the cardiac isoform of the sarcoplasmic reticulum calcium ATPase (AAV1/SERCA2a) to adult chronic heart failure patients implanted with a left ventricular assist device. The SERCA-LVAD trial was one of a program of AAV1/SERCA2a cardiac gene therapy trials including CUPID1, CUPID 2 and AGENT trials. Enroled subjects were randomised to receive a single intracoronary infusion of 1 × 1013 DNase-resistant AAV1/SERCA2a particles or a placebo solution in a double-blinded design, stratified by presence of neutralising antibodies to AAV. Elective endomyocardial biopsy was performed at 6 months unless the subject had undergone cardiac transplantation, with myocardial samples assessed for the presence of exogenous viral DNA from the treatment vector. Safety assessments including ELISPOT were serially performed. Although designed as a 24 subject trial, recruitment was stopped after five subjects had been randomised and received infusion due to the neutral result from the CUPID 2 trial. Here we describe the results from the 5 patients at 3 years follow up, which confirmed that viral DNA was delivered to the failing human heart in 2 patients receiving gene therapy with vector detectable at follow up endomyocardial biopsy or cardiac transplantation. Absolute levels of detectable transgene DNA were low, and no functional benefit was observed. There were no safety concerns in this small cohort. This trial identified some of the challenges of performing gene therapy trials in this LVAD patient cohort which may help guide future trial design.

What is the impact of e-cigarette adverts on children's perceptions of tobacco smoking? An experimental study.

OBJECTIVE: Exposure to e-cigarette adverts increases children's positive attitudes towards using them. Given the similarity in appearance between e-cigarettes and tobacco cigarettes, we examined whether exposure to e-cigarette adverts has a cross-product impact on perceptions and attitudes towards smoking tobacco cigarettes. METHODS: Children aged 11-16 (n=564) were interviewed in their homes and randomised to one of three groups: two groups saw different sets of 10 images of e-cigarette adverts and one group saw no adverts. Of the 20 e-cigarette adverts, 10 depicted the product as glamorous and 10 depicted it as healthy. The children then self-completed a questionnaire assessing perceived appeal, harms and benefits of smoking tobacco cigarettes. RESULTS: The analyses were conducted on 411 children who reported never having smoked tobacco cigarettes or used e-cigarettes. Exposure to the adverts had no impact on the appeal or perceived benefits of smoking tobacco cigarettes. While the perceived harm of smoking more than 10 cigarettes per day was similar across groups, those exposed to either set of adverts perceived the harms of smoking one or two tobacco cigarettes occasionally to be lower than those in the control group. CONCLUSIONS: This study provides the first evidence that exposure to e-cigarette adverts might influence children's perceptions of smoking tobacco cigarettes, reducing their perceived harm of occasional smoking. These results suggest the potential for e-cigarette adverts to undermine tobacco control efforts by reducing a potential barrier (ie, beliefs about harm) to occasional smoking.

Adolescents' interest in trying flavoured e-cigarettes.

BACKGROUND: More US adolescents use e-cigarettes than smoke cigarettes. Research suggests flavoured e-cigarettes appeal to youth, but little is known about perceptions of and reasons for attraction to specific flavours. METHODS: A national sample of adolescents (n=1125) ages 13-17 participated in a phone survey from November 2014 to June 2015. We randomly assigned adolescents to respond to survey items about 1 of 5 e-cigarette flavours (tobacco, alcohol, menthol, candy or fruit) and used regression analysis to examine the impact of flavour on interest in trying e-cigarettes and harm beliefs. RESULTS: Adolescents were more likely to report interest in trying an e-cigarette offered by a friend if it were flavoured like menthol (OR=4.00, 95% CI 1.46 to 10.97), candy (OR=4.53, 95% CI 1.67 to 12.31) or fruit (OR=6.49, 95% CI 2.48 to 17.01) compared with tobacco. Adolescents believed that fruit-flavoured e-cigarettes were less harmful to health than tobacco-flavoured e-cigarettes (p<0.05). Perceived harm mediated the relationship between some flavours and interest in trying e-cigarettes. A minority of adolescents believed that e-cigarettes did not have nicotine (14.6%) or did not know whether they had nicotine (3.6%); these beliefs did not vary by flavour. DISCUSSION: Candy-flavoured, fruit-flavoured and menthol-flavoured e-cigarettes appeal to adolescents more than tobacco-flavoured or alcohol-flavoured e-cigarettes. This appeal is only partially explained by beliefs about reduced harm. Given adolescents' interest in trying e-cigarettes with certain flavours, policymakers should consider restricting advertisements promoting flavoured products in media that reach large numbers of young people. Future research should examine other reasons for the appeal of individual flavours, such as novelty and perceived luxury.

Evidence of clinical efficacy of counterpulsation therapy methods.

Although heart transplantation remains the ultimate treatment for end-stage heart failure, its epidemiological impact is limited by donor organ availability. Surgical and device-based approaches have been introduced with the aim of increasing systemic perfusion and in some circumstances promoting left ventricular recovery by inducing reverse remodelling. Innovative counterpulsation devices based on the established principle of the intra-aortic balloon pump have been developed, and of these, the CardioVad and the C-Pulse System have been introduced in clinical practice with convincing evidence of haemodynamic efficacy. The evolution from pulsatile to continuous-flow left ventricular assist devices has been associated with improved survival rates during the first 2 years of support with the potential of matching heart transplantation outcomes. However, blood contact with the device remains a significant challenge despite the highly sophisticated technology currently available. Innovative extra-vascular counterpulsation devices have been shown to overcome the limitations of the intra-aortic balloon pump and rend the device suitable for prolonged support. Monitoring of the performance of these novel devices is essential, and carotid Doppler ultrasonography is of utility in assessing the haemodynamic performance of the devices in a clinical setting. Computational modelling has played a role in the simulation of these devices and should continue to assist with their optimisation and implementation in clinical practice.

Postpartum Breast Cancer and Survival in Women With Germline BRCA Pathogenic Variants.

Importance: In young-onset breast cancer (YOBC), a diagnosis within 5 to 10 years of childbirth is associated with increased mortality. Women with germline BRCA1/2 pathogenic variants (PVs) are more likely to be diagnosed with BC at younger ages, but the impact of childbirth on mortality is unknown. Objective: To determine whether time between most recent childbirth and BC diagnosis is associated with mortality among patients with YOBC and germline BRCA1/2 PVs. Design, Setting, and Participants: This prospective cohort study included women with germline BRCA1/2 PVs diagnosed with stage I to III BC at age 45 years or younger between 1950 and 2021 in the United Kingdom, who were followed up until November 2021. Data were analyzed from December 3, 2021, to November 29, 2023. Exposure: Time between most recent childbirth and subsequent BC diagnosis, with recent childbirth defined as 0 to less than 10 years, further delineated to 0 to less than 5 years and 5 to less than 10 years. Main Outcomes and Measures: The primary outcome was all-cause mortality, censored at 20 years after YOBC diagnosis. Mortality of nulliparous women was compared with the recent post partum groups and the 10 or more years post partum group. Cox proportional hazards regression analyses were adjusted for age, tumor stage, and further stratified by tumor estrogen receptor (ER) and BRCA gene status. Results: Among 903 women with BRCA PVs (mean [SD] age at diagnosis, 34.7 [6.1] years; mean [SD] follow-up, 10.8 [9.8] years), 419 received a BC diagnosis 0 to less than 10 years after childbirth, including 228 women diagnosed less than 5 years after childbirth and 191 women diagnosed 5 to less than 10 years after childbirth. Increased all-cause mortality was observed in women diagnosed within 5 to less than 10 years post partum (hazard ratio [HR], 1.56 [95% CI, 1.05-2.30]) compared with nulliparous women and women diagnosed 10 or more years after childbirth, suggesting a transient duration of postpartum risk. Risk of mortality was greater for women with ER-positive BC in the less than 5 years post partum group (HR, 2.35 [95% CI, 1.02-5.42]) and ER-negative BC in the 5 to less than 10 years post partum group (HR, 3.12 [95% CI, 1.22-7.97]) compared with the nulliparous group. Delineated by BRCA1 or BRCA2, mortality in the 5 to less than 10 years post partum group was significantly increased, but only for BRCA1 carriers (HR, 2.03 [95% CI, 1.15-3.58]). Conclusions and Relevance: These findings suggest that YOBC with germline BRCA PVs was associated with increased risk for all-cause mortality if diagnosed within 10 years after last childbirth, with risk highest for ER-positive BC diagnosed less than 5 years post partum, and for ER-negative BC diagnosed 5 to less than 10 years post partum. BRCA1 carriers were at highest risk for poor prognosis when diagnosed at 5 to less than 10 years post partum. No such associations were observed for BRCA2 carriers. These results should inform genetic counseling, prevention, and treatment strategies for BRCA PV carriers.

Rat mammary extracellular matrix composition and response to ibuprofen treatment during postpartum involution by differential GeLC-MS/MS analysis.

Breast cancer patients diagnosed within five years following pregnancy have increased metastasis and decreased survival. A hallmark of postpartum biology that may contribute to this poor prognosis is mammary gland involution, involving massive epithelial cell death and dramatic stromal remodeling. Previous studies show pro-tumorigenic properties of extracellular matrix (ECM) isolated from rodent mammary glands undergoing postpartum involution. More recent work demonstrates systemic ibuprofen treatment during involution decreases its tumor-promotional nature. Utilizing a proteomics approach, we identified relative differences in the composition of mammary ECM isolated from nulliparous rats and those undergoing postpartum involution, with and without ibuprofen treatment. GeLC-MS/MS experiments resulted in 20327 peptide identifications that mapped to 884 proteins with a <0.02% false discovery rate. Label-free quantification yielded several ECM differences between nulliparous and involuting glands related to collagen-fiber organization, cell motility and attachment, and cytokine regulation. Increases in known pro-tumorigenic ECM proteins osteopontin, tenascin-C, and laminin-α1 and pro-inflammatory proteins STAT3 and CD68 further identify candidate mediators of breast cancer progression specific to the involution window. With postpartum ibuprofen treatment, decreases in tenascin-C and three laminin chains were revealed. Our data suggest novel ECM mediators of breast cancer progression and demonstrate a protective influence of ibuprofen on mammary ECM composition.

A multiplex implantable microdevice assay identifies synergistic combinations of cancer immunotherapies and conventional drugs.

Systematically identifying synergistic combinations of targeted agents and immunotherapies for cancer treatments remains difficult. In this study, we integrated high-throughput and high-content techniques-an implantable microdevice to administer multiple drugs into different sites in tumors at nanodoses and multiplexed imaging of tumor microenvironmental states-to investigate the tumor cell and immunological response signatures to different treatment regimens. Using a mouse model of breast cancer, we identified effective combinations from among numerous agents within days. In vivo studies in three immunocompetent mammary carcinoma models demonstrated that the predicted combinations synergistically increased therapeutic efficacy. We identified at least five promising treatment strategies, of which the panobinostat, venetoclax and anti-CD40 triple therapy was the most effective in inducing complete tumor remission across models. Successful drug combinations increased spatial association of cancer stem cells with dendritic cells during immunogenic cell death, suggesting this as an important mechanism of action in long-term breast cancer control.

Mammary collagen is under reproductive control with implications for breast cancer.

Mammographically-detected breast density impacts breast cancer risk and progression, and fibrillar collagen is a key component of breast density. However, physiologic factors influencing collagen production in the breast are poorly understood. In female rats, we analyzed gene expression of the most abundantly expressed mammary collagens and collagen-associated proteins across a pregnancy, lactation, and weaning cycle. We identified a triphasic pattern of collagen gene regulation and evidence for reproductive state-dependent composition. An initial phase of collagen deposition occurred during pregnancy, followed by an active phase of collagen suppression during lactation. The third phase of collagen regulation occurred during weaning-induced mammary gland involution, which was characterized by increased collagen deposition. Concomitant changes in collagen protein abundance were confirmed by Masson's trichrome staining, second harmonic generation (SHG) imaging, and mass spectrometry. We observed similar reproductive-state dependent collagen patterns in human breast tissue obtained from premenopausal women. SHG analysis also revealed structural variation in collagen across a reproductive cycle, with higher packing density and more collagen fibers arranged perpendicular to the mammary epithelium in the involuting rat mammary gland compared to nulliparous and lactating glands. Involution was also characterized by high expression of the collagen cross-linking enzyme lysyl oxidase, which was associated with increased levels of cross-linked collagen. Breast cancer relevance is suggested, as we found that breast cancer diagnosed in recently postpartum women displayed gene expression signatures consistent with increased collagen deposition and crosslinking compared to breast cancers diagnosed in age-matched nulliparous women. Using publicly available data sets, we found this involution-like, collagen gene signature correlated with poor progression-free survival in breast cancer patients overall and in younger women. In sum, these findings of physiologic collagen regulation in the normal mammary gland may provide insight into normal breast function, the etiology of breast density, and inform breast cancer risk and outcomes.

Dental Care Use, Edentulism, and Systemic Health among Older Adults.

Past research suggests there are systematic associations between oral health and chronic illness among older adults. Although causality has not yet been credibly established, periodontitis has been found to be associated with higher risk of both heart disease and stroke. We advance this literature by estimating the direct association between dental care use and systemic health using multiple waves of the 1992 to 2016 Health and Retirement Study. Through the inclusion of individual fixed effects in our regression models, we account for unobservable time-invariant characteristics of individuals that might otherwise bias estimates of the association between dental care use and health. We find statistically significant negative associations between dental care use and the number of health conditions, self-reported overall health, the incidence of heart disease, and the incidence of stroke. In particular, the use of dental care within the past 2 y is associated with a 2.7% reduction in the likelihood of being diagnosed with a heart condition and a reduction in the likelihood of a stroke diagnosis of between 5.3% and 11.6%. We also find large positive correlations between edentulism and the measures of chronic illness. Associations from models estimated separately for men and women are qualitatively similar to one another. These findings provide additional motivation for the consideration of a Medicare dental benefit.

Hedgehog signaling promotes endoneurial fibroblast migration and Vegf-A expression following facial nerve injury.

BACKGROUND: Peripheral nerve injuries are a common clinical problem which may result in permanent loss of motor or sensory function. A better understanding of the signaling pathways that lead to successful nerve regeneration may help in discovering new therapeutic targets. The Hedgehog (Hh) signaling pathway plays significant roles in nerve development and regeneration. In a mouse model of facial nerve injury, Hedgehog-responsive fibroblasts increase in number both at the site of injury and within the distal nerve. However, the role of these cells in facial nerve regeneration is not fully understood. We hypothesize that the Hh pathway plays an angiogenic and pro-migratory role following facial nerve injury. METHODS: Hedgehog pathway modulators were applied to murine endoneurial fibroblasts isolated from the murine facial nerve. The impact of pathway modulation on endoneurial fibroblast migration and cell proliferation was assessed. Gene expression changes of known Hedgehog target genes and the key angiogenic factor Vegf-A were determined by qPCR. In vivo, mice were treated with pathway agonist (SAG21k) and injured facial nerve specimens were analyzed via immunofluorescence and in situ hybridization. RESULTS: Hedgehog pathway activation in facial nerve fibroblasts via SAG21k treatment increases Gli1 and Ptch1 expression, the rate of cellular migration, and Vegf-A expression in vitro. In vivo, expression of Gli1 and Vegf-A expression appears to increase after injury, particularly at the site of nerve injury and the distal nerve, as detected by immunofluorescence and in situ hybridization. Additionally, Gli1 transcripts co-localize with Vegf-A following transection injury to the facial nerve. DISCUSSION: These findings describe an angiogenic and pro-migratory role for the Hedgehog pathway mediated through effects on nerve fibroblasts. Given the critical role of Vegf-A in nerve regeneration, modulation of this pathway may represent a potential therapeutic target to improve facial nerve regeneration following injury.

Effect of the estrous cycle and surgical ovariectomy on energy balance, fuel utilization, and physical activity in lean and obese female rats.

This study presents an in-depth analysis of the effects of obesity on energy balance (EB) and fuel utilization in adult female rats, over the estrous cycle and immediately after surgical ovariectomy (OVX), to model pre- and postmenopausal states, respectively. Female Wistar rats were fed a high-fat (46%) diet for 16 wk to produce mature lean and obese animals. Stage of estrous was identified by daily vaginal lavage, while energy intake (EI), total energy expenditure (TEE), and fuel utilization were monitored in a multichamber indirect calorimeter and activity was monitored by infrared beam breaks. Metabolic monitoring studies were repeated during the 3-wk period of rapid OVX-induced weight gain. Component analysis of TEE was performed to determine the nonresting and resting portions of energy expenditure. Obesity was associated with a greater fluctuation in EB across the estrous cycle. Cycling obese rats were less active, expended more energy per movement, and oxidized more carbohydrate than lean rats. The changes in EB over the cycle in lean and obese rats were driven by changes in EI. Finally, OVX induced a large positive energy imbalance in obese and lean rats. This resulted primarily from an increase in EI in both groups, with little change in TEE following OVX. These observations reveal a dominant effect of obesity on EB, fuel utilization, and activity levels in cycling rats, which has implications for studies focused on obesity and EB in female rodents.

Benign mammary epithelial cells enhance the transformed phenotype of human breast cancer cells.

BACKGROUND: Recent research has yielded a wealth of data underscoring the key role of the cancer microenvironment, especially immune and stromal cells, in the progression of cancer and the development of metastases. However, the role of adjacent benign epithelial cells, which provide initial cell-cell contacts with cancer cells, in tumor progression has not been thoroughly examined. In this report we addressed the question whether benign MECs alter the transformed phenotype of human breast cancer cells. METHODS: We used both in vitro and in vivo co-cultivation approaches, whereby we mixed GFP-tagged MCF-10A cells (G2B-10A), as a model of benign mammary epithelial cells (MECs), and RFP-tagged MDA-MB-231-TIAS cells (R2-T1AS), as a model of breast cancer cells. RESULTS: The in vitro studies showed that G2B-10A cells increase the colony formation of R2-T1AS cells in both soft agar and clonogenicity assays. Conditioned media derived from G2B-10A cells enhanced colony formation of R2-T1AS cells, whereas prior paraformaldehyde (PFA) fixation of G2B-10A cells abrogated this enhancement effect. Moreover, two other models of benign MECs, MCF-12A and HuMECs, also enhanced R2-T1AS colony growth in soft agar and clonogenicity assays. These data reveal that factors secreted by benign MECs are responsible for the observed enhancement of the R2-T1AS transformed phenotype. To determine whether G2B-10A cells enhance the tumorigenic growth of co-injected R2-T1AS cells in vivo, we used the nude mouse xenograft assay. Co-injecting R2-T1AS cells with G2B-10A cells +/- PFA-fixation, revealed that G2B-10A cells promoted a ~3-fold increase in tumor growth, irrespective of PFA pre-treatment. These results indicate that soluble factors secreted by G2B-10A cells play a less important role in promoting R2-T1AS tumorigenesis in vivo, and that additional components are operative in the nude mouse xenograft assay. Finally, using array analysis, we found that both live and PFA-fixed G2B-10A cells induced R2-T1AS cells to secrete specific cytokines (IL-6 and GM-CSF), suggesting that cell-cell contact activates R2-T1AS cells. CONCLUSIONS: Taken together, these data shift our understanding of adjacent benign epithelial cells in the cancer process, from passive, noncontributory cells to an active and tumor-promoting vicinal cell population that may have significant effects early, when benign cells outnumber malignant cells.

Pregnancy and breast cancer: when they collide.

Women of childbearing age experience an increased breast cancer risk associated with a completed pregnancy. For younger women, this increase in breast cancer risk is transient and within a decade after parturition a cross over effect results in an ultimate protective benefit. The post-partum peak of increased risk is greater in women with advanced maternal age. Further, their lifetime risk for developing breast cancer remains elevated for many years, with the cross over to protection occurring decades later or not at all. Breast cancers diagnosed during pregnancy and within a number of years post-partum are termed pregnancy-associated or PABC. Contrary to popular belief, PABC is not a rare disease and could affect up to 40,000 women in 2009. The collision between pregnancy and breast cancer puts women in a fear-invoking paradox of their own health, their pregnancy, and the outcomes for both. We propose two distinct subtypes of PABC: breast cancer diagnosed during pregnancy and breast cancer diagnosed post-partum. This distinction is important because emerging epidemiologic data highlights worsened outcomes specific to post-partum cases. We reported that post-partum breast involution may be responsible for the increased metastatic potential of post-partum PABC. Increased awareness and detection, rationally aggressive treatment, and enhanced understanding of the mechanisms are imperative steps toward improving the prognosis for PABC. If we determine the mechanisms by which involution promotes metastasis of PABC, the post-partum period can be a window of opportunity for intervention strategies.

Mucosal Immunity and Liver Metabolism in the Complex Condition of Lactation Insufficiency.

Lactation insufficiency is variously defined and includes the inability to produce milk, not producing enough milk to exclusively meet infant growth requirements, and pathological interruption of lactation (e.g., mastitis). Of women with intent-to-breastfeed, lactation insufficiency has been estimated to affect 38%-44% of newly postpartum women, likely contributing to the nearly 60% of infants that are not breastfed according to the World Health Organization's guidelines. To date, research and clinical practice aimed at improving feeding outcomes have focused on hospital lactation support and education, with laudable results. However, researchers' reports of recent rodent studies concerning fundamental lactation biology have suggested that the underlying pathologies of lactation insufficiency may be more nuanced than is currently appreciated. In this article, we identify mucosal biology of the breast and lactation-specific liver biology as two under-researched aspects of lactation physiology. Specifically, we argue that further scientific inquiry into reproductive state-dependent regulation of immunity in the human breast will reveal insights into novel immune based requirements for healthy lactation. Additionally, our synthesis of the literature supports the hypothesis that the liver is an essential player in lactation-highlighting the potential that pathologies of the liver may also be associated with lactation insufficiency. More research into these biologic underpinnings of lactation is anticipated to provide new avenues to understand and treat lactation insufficiency.

Exclusive Breastfeeding Rates at 6 Weeks Postpartum as a Function of Preconception Body Mass Index Are Not Impacted by Postpartum Obstetrical Practices or Routines.

Objective: Women with overweight/obesity have significantly lower rates of exclusive breastfeeding (EBF) at 6 weeks postpartum compared with women of normal weight. We sought to determine whether differences in Baby-Friendly Hospital Initiative (BFHI) adherence, obstetric practices, or social support explain these weight-related EBF disparities. Methods: One hundred forty-two healthy women who intended EBF (61 normal weight, 50 overweight, and 31 obese by preconception body mass index [BMI]) were enrolled in a cross-sectional study. Obstetric data were collected and participants completed modified Infant Feeding Practices Study II surveys at 6 weeks postpartum. Results: Women with obesity were significantly less likely to undergo spontaneous labor and more likely to receive synthetic oxytocin and epidural anesthesia compared with women with overweight or normal weight. Women who were overweight were less likely to report extended family support for breastfeeding compared with women with obesity or normal weight; however, BFHI components and composite BFHI score did not differ by maternal BMI. Furthermore, regardless of BMI, women with greater adherence to BFHI practices were more likely to be EBF at 6 weeks postpartum (p-value <0.001). Nonetheless, at 6 weeks postpartum, women with obesity were expressing milk more frequently and less likely to have met their own breastfeeding goals compared with women with overweight and normal weight. Conclusions: Differences in EBF rates by BMI were not explained by BFHI adherence or obstetric practices. These data suggest physiological differences, rather than intrapartum practices and support services, may explain differences in EBF rates by maternal overweight/obesity.

Group treatments for sensitive health care problems: a randomised controlled trial of group versus individual physiotherapy sessions for female urinary incontinence.

BACKGROUND: The aim was to compare effectiveness of group versus individual sessions of physiotherapy in terms of symptoms, quality of life, and costs, and to investigate the effect of patient preference on uptake and outcome of treatment. METHODS: A pragmatic, multi-centre randomised controlled trial in five British National Health Service physiotherapy departments. 174 women with stress and/or urge incontinence were randomised to receive treatment from a physiotherapist delivered in a group or individual setting over three weekly sessions. Outcome were measured as Symptom Severity Index; Incontinence-related Quality of Life questionnaire; National Health Service costs, and out of pocket expenses. RESULTS: The majority of women expressed no preference (55%) or preference for individual treatment (36%). Treatment attendance was good, with similar attendance with both service delivery models. Overall, there were no statistically significant differences in symptom severity or quality of life outcomes between the models. Over 85% of women reported a subjective benefit of treatment, with a slightly higher rating in the individual compared with the group setting. When all health care costs were considered, average cost per patient was lower for group sessions (Mean cost difference 52.91 pounds 95%, confidence interval ( 25.82 pounds- 80.00 pounds)). CONCLUSION: Indications are that whilst some women may have an initial preference for individual treatment, there are no substantial differences in the symptom, quality of life outcomes or non-attendance. Because of the significant difference in mean cost, group treatment is recommended. TRIAL REGISTRATION NUMBER: ISRCTN 16772662.

Association Between Postpartum Breast Cancer Diagnosis and Metastasis and the Clinical Features Underlying Risk.

Importance: In women 45 years or younger, breast cancer diagnosis after childbirth increases the risk for metastasis and death, yet limited data exist to define this window of risk and associated prognostic factors. Objective: To assess the window of elevated risk for metastasis following a postpartum breast cancer (PPBC) diagnosis and whether clinical prognostic factors are associated with the increased risk. Design, Setting, and Participants: This multicenter cohort study conducted using cases from the Colorado Young Women's Breast Cancer Cohort diagnosed between January 1, 1981, and December 31, 2014, included 701 women 45 years or younger with stage I to III invasive breast cancer for whom parity data, including time of last childbirth, were available. Data analysis was conducted from July 1 to September 30, 2017. This study involved a tertiary care academic hospital-based breast center and its regional affiliates with cases from the greater Rocky Mountain region. Exposures: Primary exposures were prior childbirth or no childbirth, time between most recent childbirth and breast cancer diagnosis, and time between breast cancer diagnosis and metastasis. Main Outcomes and Measures: The primary outcome was distant metastasis-free survival. Results: A total of 701 women 45 years or younger from the greater Rocky Mountain states region were included in the analysis; mean (SD) age at diagnosis was 37.9 (5.1) years. Breast cancer diagnosis within 10 years after parturition was associated with elevated risk for metastasis, particularly in women with stage I or II disease. In addition, women with PPBC diagnosed within 10 years of a completed pregnancy that was estrogen receptor-positive showed distant metastasis-free survival similar to that of nulliparous patients with estrogen receptor-negative cancer, and women with estrogen receptor-negative PPBC had further reduced metastasis-free survival. Moreover, women with PPBC had increased lymphovascular invasion and lymph node involvement. In addition, tumor-associated Ki67 positivity identified 129 patients with luminal B cancer in the cohort that, independent of parity status, had poorer prognosis compared with patients with luminal A cancer, although it did not reach statistical significance. Conclusions and Relevance: Diagnosis of PPBC within 10 years post partum appears to be associated with an increased risk for metastasis. This increased risk was highest in stages I and II cancer at diagnosis and present in both patients with estrogen receptor-positive and estrogen receptor-negative cancer, persisting in estrogen receptor-positive cases for up to 15 years after diagnosis. Postpartum breast cancer diagnoses were not associated with increased Ki67 index but were associated with increased lymphovascular invasion and lymph node involvement compared with breast cancer in nulliparous patients.

Computational study of aortic hemodynamics for patients with an abnormal aortic valve: The importance of secondary flow at the ascending aorta inlet.

Blood flow in the aorta is helical, but most computational studies ignore the presence of secondary flow components at the ascending aorta (AAo) inlet. The aim of this study is to ascertain the importance of inlet boundary conditions (BCs) in computational analysis of flow patterns in the thoracic aorta based on patient-specific images, with a particular focus on patients with an abnormal aortic valve. Two cases were studied: one presenting a severe aortic valve stenosis and the other with a mechanical valve. For both aorta models, three inlet BCs were compared; these included the flat profile and 1D through-plane velocity and 3D phase-contrast magnetic resonance imaging derived velocity profiles, with the latter being used for benchmarking. Our results showed that peak and mean velocities at the proximal end of the ascending aorta were underestimated by up to 41% when the secondary flow components were neglected. The results for helical flow descriptors highlighted the strong influence of secondary velocities on the helical flow structure in the AAo. Differences in all wall shear stress (WSS)-derived indices were much more pronounced in the AAo and aortic arch (AA) than in the descending aorta (DAo). Overall, this study demonstrates that using 3D velocity profiles as inlet BC is essential for patient-specific analysis of hemodynamics and WSS in the AAo and AA in the presence of an abnormal aortic valve. However, predicted flow in the DAo is less sensitive to the secondary velocities imposed at the inlet; hence, the 1D through-plane profile could be a sufficient inlet BC for studies focusing on distal regions of the thoracic aorta.