Experiences of cohabiting partners of women diagnosed with cancer during pregnancy: a qualitative study.

PURPOSE: When a pregnant woman is diagnosed with cancer, she faces complex and unique challenges while navigating both obstetric and oncological care. Despite often being the primary support for women diagnosed with cancer during pregnancy (CDP), little is known about the experiences of their partners. We undertook an in-depth exploration of the experiences of partners of women diagnosed with CDP in Australia. METHODS: Semi-structured interviews were conducted with partners of women diagnosed with CDP treated in Australia. Interviews explored partners' inclusion in decision making and communication with health professionals and their own coping experiences. Data were analysed thematically. RESULTS: Data from interviews with 12 male partners (N = 12) of women diagnosed with CDP were analysed. Two unique themes relevant to partners were identified: 'Partners require support to adjust to changing roles and additional burdens' and 'Treating the couple as a team facilitates agency and coping, but partners' needs are placed second by all'. CONCLUSION: Partners of women diagnosed with CDP commonly experience unique stressors and a substantial shift in previously established roles across multiple domains including medical advocacy, household coordination and parenting. Partners' coping is interlinked with how the woman diagnosed with CDP is coping. Inclusion of partners in treatment decisions and communications, and considering partners' wellbeing alongside that of the woman with CDP, is likely to be supportive for partners. In turn, this is likely to enhance the quality of support that women diagnosed with CDP receive from their partners.

Psychiatric disorders in childhood cancer survivors: A retrospective matched cohort study of inpatient hospitalisations and community-based mental health services utilisation in Western Australia.

OBJECTIVE: We examined the impact of long-term mental health outcomes on healthcare services utilisation among childhood cancer survivors in Western Australia using linked hospitalisations and community-based mental healthcare records from 1987 to 2019. METHOD: The study cohort included 2977 childhood cancer survivors diagnosed with cancer at age < 18 years in Western Australia from 1982 to 2014 and a matched non-cancer control group of 24,994 individuals. Adjusted hazard ratios of recurrent events were estimated using the Andersen-Gill model. The cumulative burden of events over time was assessed using the method of mean cumulative count. The annual percentage change in events was estimated using the negative binomial regression model. RESULTS: The results showed higher community-based service contacts (rate/100 person-years: 30.2, 95% confidence interval = [29.7-30.7] vs 22.8, 95% confidence interval = [22.6-22.9]) and hospitalisations (rate/1000 person-years: 14.8, 95% confidence interval = [13.6-16.0] vs 12.7, 95% confidence interval = [12.3-13.1]) in childhood cancer survivors compared to the control group. Childhood cancer survivors had a significantly higher risk of any event (adjusted hazard ratio = 1.5, 95% confidence interval = [1.1-2.0]). The cumulative burden of events increased with time since diagnosis and across age groups. The annual percentage change for hospitalisations and service contacts significantly increased over time (p < 0.05). Substance abuse was the leading cause of hospitalisations, while mood/affective and anxiety disorders were common causes of service contacts. Risk factors associated with increased service events included cancer diagnosis at age < 5 years, leukaemia diagnosis, high socioeconomic deprivation, and an attained age of < 18 years. CONCLUSIONS: The elevated utilisation of healthcare services observed among childhood cancer survivors emphasises the need for periodic assessment of psychiatric disorders, particularly in high-risk survivors, to facilitate early management and optimise healthcare resources.

Getting the MOST out of follow-up: a randomized controlled trial comparing 3 monthly nurse led follow-up via telehealth, including monitoring CA125 and patient reported outcomes using the MOST (Measure of Ovarian Symptoms and Treatment concerns) with routine clinic based or telehealth follow-up, after completion of first line chemotherapy in patients with epithelial ovarian cancer.

BACKGROUND: Physical symptoms, anxiety, depression, fear of recurrence, sexual dysfunction, and social withdrawal are common in women after treatment for ovarian cancer. Most patients would like and need help dealing with these symptoms. The traditional model of follow-up care is unstructured and largely focused on diagnosing recurrent disease, and most oncologists lack skills to identify and manage psychosocial issues. No high quality prospective clinical trials have been conducted to determine the optimal follow-up regimen or the cost effectiveness of ovarian cancer surveillance strategies. PRIMARY OBJECTIVES: To assess emotional wellbeing, acceptability, safety, and cost effectiveness of nurse led follow-up via telehealth for women with ovarian cancer following completion of primary treatment. STUDY HYPOTHESIS: We hypothesize that compared with routine clinic based follow-up, nurse led follow-up via telehealth, including serum CA125 monitoring and completion of a patient reported outcome instrument, the Measure of Ovarian Symptoms and Treatment concerns-Surveillance (MOST-S26), will improve emotional wellbeing in women with ovarian cancer; be feasible, safe, acceptable, and not delay the time to diagnosis of recurrent disease; will result in greater patient satisfaction; will identify more patients with psychological distress, lead to better care, and improved psychological outcomes; and be cost-effective. TRIAL DESIGN: Phase II multicenter randomized trial comparing 3 monthly nurse led telehealth consultations that include serum CA125 monitoring and completion of the MOST-S26, with routine clinic based follow-up. The allocation ratio will be 1:1. MAJOR INCLUSION/EXCLUSION CRITERIA: Eligible patients will be women with high grade epithelial ovarian cancer who have normalized serum CA125 (to <35 kU/L) at completion of first line chemotherapy. PRIMARY ENDPOINTS: Emotional wellbeing at 12 months. SAMPLE SIZE: 150 patients. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: July 2023. Results expected in 2025, 24 months after the last participant is enrolled. TRIAL REGISTRATION: ACTRN12620000332921.

Perinatal outcomes of women with gestational breast cancer in Australia and New Zealand: A prospective population-based study.

OBJECTIVE: To determine the epidemiology, clinical management, and outcomes of women with gestational breast cancer (GBC). METHODS: A population-based prospective cohort study was conducted in Australia and New Zealand between 2013 and 2014 using the Australasian Maternity Outcomes Surveillance System (AMOSS). Women who gave birth with a primary diagnosis of breast cancer during pregnancy were included. Data were collected on demographic and pregnancy factors, GBC diagnosis, obstetric and cancer management, and perinatal outcomes. The main outcome measures were preterm birth, maternal complications, breastfeeding, and death. RESULTS: Forty women with GBC (incidence 7.5/100 000 women giving birth) gave birth to 40 live-born babies. Thirty-three (82.5%) women had breast symptoms at diagnosis. Of 27 women diagnosed before 30 weeks' gestation, 85% had breast surgery and 67% had systemic therapy during pregnancy. In contrast, all 13 women diagnosed from 30 weeks had their cancer management delayed until postdelivery. There were 17 preterm deliveries; 15 were planned. Postpartum complications included the following: hemorrhage (n = 4), laparotomy (n = 1), and thrombocytopenia (n = 1). There was one late maternal death. Eighteen (45.0%) women initiated breastfeeding, including 12 of 23 women who had antenatal breast surgery. There were no perinatal deaths or congenital malformations, but 42.5% of babies were preterm, and 32.5% were admitted for higher-level neonatal care. CONCLUSIONS: Gestational breast cancer diagnosed before 30 weeks' gestation was associated with surgical and systemic cancer care during pregnancy and planned preterm birth. In contrast, cancer treatment was deferred to postdelivery for women diagnosed from 30 weeks, reflecting the complexity of managing expectant mothers with GBC in multidisciplinary care settings.

Isolation experienced by women with gestational cancer: could peer support and tailored information be the answer?

Women diagnosed with cancer during pregnancy (gestational cancer) are a small but vulnerable population, with experts suggesting they require greater psycho-social support than either other women with cancer or other pregnant women. However, information on their psychological needs remains sparse. This commentary describes our work exploring the psychological needs of women diagnosed with gestational cancer, areas of unmet need we identified, and our recommendations for future programs and research. We conducted in-depth, semi-structured interviews with 23 Australian women diagnosed with gestational cancer in the preceding 5 years. Our findings depicted a group of women for whom cancer diagnosis and treatment had resulted in a sense of isolation and loneliness. Women reported seeking tailored information about their condition and treatments as well as one-on-one peer support with other gestational cancer survivors, which was challenging for them to access and which existing services struggled to provide. To address these unmet needs, innovative solutions may be necessary. Technology has the potential to connect and match women with one-to-one peer support, and research exploring the efficacy and acceptability of such interventions is required. Creative solutions, such as virtual resource hubs monitored or moderated by experts, would potentially meet the information needs of this group. However, as gestational cancer is relatively rare, the development and evaluation of such interventions would require a collaborative effort across multiple sites, as well as international collaboration and data pooling.

Cancer during pregnancy: A qualitative study of healthcare experiences of Australian women.

OBJECTIVES: To identify features enhancing the quality of healthcare experiences for women with gestational cancer, and explore the impact of the heterogeneous Australian healthcare system on those experiences. METHODS: Semi-structured, qualitative interviews were conducted with women diagnosed with any cancer during pregnancy in the last five years. Recruitment occurred during 2018-2019 via social media and professional, clinical and community networks. Questions related to women's experiences of their healthcare, wellbeing and psychosocial needs. Interviews were analysed thematically. RESULTS: Study participants (n = 23) received treatment in the private sector (n = 10), public sector (n = 8), or both (n = 5). Five interview themes were found: Control over healthcare; Trust in clinicians, hospitals and systems; Coordination of care; An uncommon diagnosis; Holistic, future-oriented care. Women were most likely to have had a positive healthcare experience when (a)care was well-coordinated and adjusted to meet their unique needs/challenges, and (b)women perceived their care went beyond their immediate medical needs and encompassed future psychosocial wellbeing, including preparation for postpartum challenges. CONCLUSION: Existing 'usual care' in the public and/or private sector for both the pregnancy and the cancer is insufficient to meet these women's needs. Prioritising psychological wellbeing including psychosocial needs, and communication and planning around fertility and postnatal challenges are essential for this population.

Reproductive outcomes following a stem cell transplant for a haematological malignancy in female cancer survivors: a systematic review and meta-analysis.

PURPOSE: The use of high-dose chemotherapy and radiotherapy combined with haematopoietic stem cell transplantation (HSCT) may negatively affect a woman's reproductive potential. Reproductive outcomes such as infertility are a major concern for women who undergo treatment for a haematological cancer diagnosis. OBJECTIVE: This systematic review and meta-analysis explores reproductive outcomes following a haematological cancer requiring HSCT. METHODS: Electronic databases were searched to identify studies that reported on reproductive outcomes after treatment for a haematological cancer diagnosis. Studies were included that reported on pregnancy and reproductive outcomes following HSCT for a haematological malignancy. RESULTS: The meta-analysis included 14 studies, collectively involving 744 female patients. The subgroup analysis showed an overall pooled estimated pregnancy rate, for autologous or allogeneic HSCT recipients, of 22.7% (n = 438). There were 25% (n = 240) of women who became pregnant after autologous HSCT compared with 22% (n = 198) who subsequently became pregnant following allogeneic HSCT. CONCLUSIONS: This meta-analysis reflects low pregnancy rates for cancer survivors desiring a family. However, live births are improving over time with new technology and novel therapies. Hence, female cancer patients should be offered timely discussions, counselling and education around fertility preservation options prior to starting treatment with gonadotoxic therapy.

Stress Hormones Epinephrine and Corticosterone Selectively Modulate Herpes Simplex Virus 1 (HSV-1) and HSV-2 Productive Infections in Adult Sympathetic, but Not Sensory, Neurons.

Herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) infect and establish latency in peripheral neurons, from which they can reactivate to cause recurrent disease throughout the life of the host. Stress is associated with the exacerbation of clinical symptoms and the induction of recurrences in humans and animal models. The viruses preferentially replicate and establish latency in different subtypes of sensory neurons, as well as in neurons of the autonomic nervous system that are highly responsive to stress hormones. To determine if stress-related hormones modulate productive HSV-1 and HSV-2 infections within sensory and autonomic neurons, we analyzed viral DNA and the production of viral progeny after treatment of primary adult murine neuronal cultures with the stress hormones epinephrine and corticosterone. Both sensory trigeminal ganglion (TG) and sympathetic superior cervical ganglion (SCG) neurons expressed adrenergic receptors (activated by epinephrine) and the glucocorticoid receptor (activated by corticosterone). Productive HSV infection colocalized with these receptors in SCG but not in TG neurons. In productively infected neuronal cultures, epinephrine treatment significantly increased the levels of HSV-1 DNA replication and production of viral progeny in SCG neurons, but no significant differences were found in TG neurons. In contrast, corticosterone significantly decreased the levels of HSV-2 DNA replication and production of viral progeny in SCG neurons but not in TG neurons. Thus, the stress-related hormones epinephrine and corticosterone selectively modulate acute HSV-1 and HSV-2 infections in autonomic, but not sensory, neurons.IMPORTANCE Stress exacerbates acute disease symptoms resulting from HSV-1 and HSV-2 infections and is associated with the appearance of recurrent skin lesions in millions of people. Although stress hormones are thought to impact HSV-1 and HSV-2 through immune system suppression, sensory and autonomic neurons that become infected by HSV-1 and HSV-2 express stress hormone receptors and are responsive to hormone fluctuations. Our results show that autonomic neurons are more responsive to epinephrine and corticosterone than are sensory neurons, demonstrating that the autonomic nervous system plays a substantial role in HSV pathogenesis. Furthermore, these results suggest that stress responses have the potential to differentially impact HSV-1 and HSV-2 so as to produce divergent outcomes of infection.

Perceived influence of psychological consultation on psychological well-being, body image, and intimacy following bilateral prophylactic mastectomy: A qualitative analysis.

OBJECTIVE: This study explored whether psychological consultation offered to women prior to bilateral prophylactic mastectomy (BPM) appeared to provide psychosocial benefit to younger women (<35 years) at high risk of developing breast cancer due to a mutation or family history. METHODS: Qualitative interviews guided by interpretative phenomenological analysis were conducted retrospectively with 26 women who had undergone BPM. Participants were recruited from New Zealand and Australia, via a genetics clinic, registry, research cohort, and online. RESULTS: Three themes were identified: psychological well-being and adjustment, satisfaction with intimacy, and body image. Participants that had seen a psychologist reported being more prepared for BPM and appeared to adjust positively post-surgery. They appeared to have improved psychological well-being, reported satisfaction with intimacy, and a more positive body image, compared with those who had no support. CONCLUSIONS: Women who undergo psychological consultation prior to BPM appear to adjust positively after surgery. Implications for practice include standard psychological consultation for younger women (>35 years) considering BPM.

Out-of-pocket expenses experienced by rural Western Australians diagnosed with cancer.

PURPOSE: Out-of-pocket expenses (OOPE) can have a significant impact on patients' experiences of cancer treatment. This cross-sectional study sought to quantify the OOPEs experienced by rural cancer patients in Western Australia (WA), and determine factors that contributed to higher OOPE. METHODS: Four hundred people diagnosed with breast, lung, colorectal or prostate cancer who resided in selected rural regions of WA were recruited through the WA Cancer Registry and contacted at least 3 months after diagnosis to report the medical OOPE (such as surgery or chemotherapy, supportive care, medication and tests) and non-medical OOPE (such as travel costs, new clothing and utilities) they had experienced as a result of accessing and receiving treatment. Bootstrapped t tests identified demographic, financial and treatment-related factors to include in multivariate analysis, performed using log-linked generalised linear models with gamma distribution. RESULTS: After a median 21 weeks post-diagnosis, participants experienced an average OOPE of AU$2179 (bootstrapped 95% confidence interval $1873-$2518), and 45 (11%) spent more than 10% of their household income on these expenses. Participants likely to experience higher total OOPE were younger than 65 years (p = 0.008), resided outside the South West region (p = 0.007) and had private health insurance (PHI) (p < 0.001). CONCLUSIONS: Rural WA cancer patients experience significant OOPE following their diagnosis. The impact these expenses have on patient wellbeing and their treatment decisions need to be further explored.

Influences on Satisfaction with Reconstructed Breasts and Intimacy in Younger Women Following Bilateral Prophylactic Mastectomy: a Qualitative Analysis.

PURPOSE: The aim of this study was to explore the influences on satisfaction with reconstructed breasts and intimacy following bilateral prophylactic mastectomy (BPM) in younger women (< 35) with a strong family history of breast cancer. METHODS: Twenty-six women who had undergone BPM between 1 and6 years ago were recruited from New Zealand and Australia through a genetics clinic, registry, research cohort, and online (Mage = 31). Twenty-three were BRCA mutation carriers. Qualitative interviews guided by interpretative phenomenological analysis were conducted. RESULTS: Four themes were identified: satisfaction with breasts before surgery, outcome expectations, type of mastectomy, and open communication. Women who liked their breasts pre-BPM appeared less satisfied with their reconstructed breasts post-surgery, and women who disliked their breasts before BPM were more satisfied with their reconstructed breasts. Women with unrealistic expectations concerning the look and feel of reconstructed breasts were often unhappy with their reconstructed breasts and felt they did not meet their expectations. Unrealistic photos of breast reconstruction and satisfactory communication of realistic outcome expectations by surgeons or psychologists also appeared to influence satisfaction. Communication with partners prior to BPM appeared to improve satisfaction with intimacy post-BPM. CONCLUSIONS: The findings suggest that satisfaction with reconstructed breasts for younger women post-BPM appeared to be influenced by realistic outcome expectations and communication with others concerning reconstructed breast appearance and intimacy post-BPM. Implications for practice include discussion of realistic reconstructed breast appearance, referral to a psychologist to discuss sensitive issues, and accurate communication of surgical risks and consequences.

Challenges of lymphoedema management in an ageing population.

The risk of developing chronic oedema increases with age. Many factors affect the successful management of this condition, which a robust holistic assessment will identify. This article discusses some of the challenges and complications associated with managing this long-term condition, alongside comorbidities and the effects of ageing. It will consider the implications of wider issues such as social care and the current healthcare economy. The challenges of lymphoedema management can be overcome by offering a collaborative approach to care. This can be achieved by specialist practitioners offering support, advice and guidance on how to ensure satisfactory outcomes for patients in a timely manner.

Admissions for antibiotic-resistant infections in cancer patients during first year of cancer diagnosis: a cross-sectional study.

In this study, linked Western Australian health data were used to determine presence of an antibiotic-resistant infection (ABRI) for all people diagnosed with a primary invasive cancer in 2009. Of 10 858 cancer cases, 154 (1.42%) had an ABRI. Patients with an ABRI were older (71.5 vs 66 years), and more had died in the year following diagnosis (37.7 vs 20.2%, P < 0.001). The ABRI cohort had a higher proportion of colorectal, genitourinary and haematological cancers (19.5 vs 11.9%; 14.3 vs 9.7% and 16.9 vs 5.8%, respectively). Hospital admissions with an ABRI were longer (22.3 vs 2.9 days, P < 0.001) and had a higher proportion of unplanned admissions (60.3 vs 15.2%), admissions through emergency department (36.8 vs 8.3%) and intensive care admissions (14.9 vs 1.7%, P < 0.001). Patients with solid tumours who developed an ABRI were more likely to have received chemotherapy (35.9 vs 27.8%, P = 0.04). In haematological cancer patients, a greater proportion of the admissions with an ABRI occurred after radiation therapy or chemotherapy (P = 0.01 and P = 0.005, respectively). This study is the first to report population-level data on ABRI in cancer patients. Patients with an ABRI had more hospital admissions and poorer outcomes.

Herpes Simplex Virus 1 Reactivates from Autonomic Ciliary Ganglia Independently from Sensory Trigeminal Ganglia To Cause Recurrent Ocular Disease.

Herpes simplex virus 1 (HSV-1) and HSV-2 establish latency in sensory and autonomic neurons after ocular or genital infection, but their recurrence patterns differ. HSV-1 reactivates from latency to cause recurrent orofacial disease, and while HSV-1 also causes genital lesions, HSV-2 recurs more efficiently in the genital region and rarely causes ocular disease. The mechanisms regulating these anatomical preferences are unclear. To determine whether differences in latent infection and reactivation in autonomic ganglia contribute to differences in HSV-1 and HSV-2 anatomical preferences for recurrent disease, we compared HSV-1 and HSV-2 clinical disease, acute and latent viral loads, and viral gene expression in sensory trigeminal and autonomic superior cervical and ciliary ganglia in a guinea pig ocular infection model. HSV-2 produced more severe acute disease, correlating with higher viral DNA loads in sensory and autonomic ganglia, as well as higher levels of thymidine kinase expression, a marker of productive infection, in autonomic ganglia. HSV-1 reactivated in ciliary ganglia, independently from trigeminal ganglia, to cause more frequent recurrent symptoms, while HSV-2 replicated simultaneously in autonomic and sensory ganglia to cause more persistent disease. While both HSV-1 and HSV-2 expressed the latency-associated transcript (LAT) in the trigeminal and superior cervical ganglia, only HSV-1 expressed LAT in ciliary ganglia, suggesting that HSV-2 is not reactivation competent or does not fully establish latency in ciliary ganglia. Thus, differences in replication and viral gene expression in autonomic ganglia may contribute to differences in HSV-1 and HSV-2 acute and recurrent clinical disease.

Designing and implementing a bundle of care for patients with early-stage breast cancer: lessons from a pilot program.

We present a case study on the design and implementation of a value-based bundled package of care for patients with early-stage breast cancer treated in the private health sector in Australia. Value-based healthcare is an essential change to how we deliver healthcare, shifting the focus from paying for individual services provided to a focus on the health outcomes gained over a full cycle of care. The Australian health system has unintentionally created barriers to value-based cancer care through fragmented care pathways and complex funding arrangements where patients can unexpectedly encounter high out-of-pocket costs. A team of clinicians, service providers, health systems and funding experts, private health insurers and consumers have collaborated to design and pilot a complete bundled package of care for breast cancer patients which aims to address these challenges. With 40 patients recruited to date, early evaluation results show positive patient experience of 'joined-up' care and financial transparency. This case study provides a high-level overview of the approach taken to design and implement the Breast Cancer Bundle and the lessons learned for its expansion in both public and private settings.

Contrast-enhanced mammography (CEM) versus MRI for breast cancer staging: detection of additional malignant lesions not seen on conventional imaging.

BACKGROUND: Contrast-enhanced mammography (CEM) is more available than MRI for breast cancer staging but may not be as sensitive in assessing disease extent. We compared CEM and MRI in this setting. METHODS: Fifty-nine women with invasive breast cancer underwent preoperative CEM and MRI. Independent pairs of radiologists read CEM studies (after reviewing a 9-case set prior to study commencement) and MRI studies (with between 5 and 25 years of experience in breast imaging). Additional lesions were assigned National Breast Cancer Centre (NBCC) scores. Positive lesions (graded NBCC ≥ 3) likely to influence surgical management underwent ultrasound and/or needle biopsy. True-positive lesions were positive on imaging and pathology (invasive or in situ). False-positive lesions were positive on imaging but negative on pathology (high-risk or benign) or follow-up. False-negative lesions were negative on imaging (NBCC < 3 or not identified) but positive on pathology. RESULTS: The 59 women had 68 biopsy-proven malignant lesions detected on mammography/ultrasound, of which MRI demonstrated 66 (97%) and CEM 67 (99%) (p = 1.000). Forty-one additional lesions were detected in 29 patients: six of 41 (15%) on CEM only, 23/41 (56%) on MRI only, 12/41 (29%) on both; CEM detected 1/6 and MRI 6/6 malignant additional lesions (p = 0.063), with a positive predictive value (PPV) of 1/13 (8%) and 6/26 (23%) (p = 0.276). CONCLUSIONS: While MRI and CEM were both highly sensitive for lesions detected at mammography/ultrasound, CEM may not be as sensitive as MRI in detecting additional otherwise occult foci of malignancy. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry: ACTRN 12613000684729.

Accuracy and precision of contrast enhanced mammography versus MRI for predicting breast cancer size: how "good" are they really?

OBJECTIVE: To evaluate and compare the accuracy and precision of contrast-enhanced mammography (CEM) vs MRI to predict the size of biopsy-proven invasive breast cancer. METHODS: Prospective study, 59 women with invasive breast cancer on needle biopsy underwent CEM and breast MRI. Two breast radiologists read each patient's study, with access limited to one modality. CEM lesion size was measured using low-energy and recombined images and on MRI, the first post-contrast series. Extent of abnormality per quadrant was measured for multifocal lesions. Reference standards were size of largest invasive malignant lesion, invasive (PathInvasive) and whole (PathTotal). Pre-defined clinical concordance ±10 mm. RESULTS: Mean patient age 56 years, 42 (71%) asymptomatic. Lesions were invasive ductal carcinoma 40 (68%) with ductal carcinoma in situ (31/40) in 78%, multifocal in 12 (20%). Median lesion size was 17 mm (invasive) and 27 mm (total), range (5-125 mm). Lin's concordance correlation coefficients for PathTotal 0.75 (95% CI 0.6, 0.84) and 0.71 (95% CI 0.56, 0.82) for MRI and contrast-enhanced spectral mammography (CESM) respectively. Mean difference for total size, 3% underestimated and 4% overestimated, and for invasive 41% and 50% overestimate on MRI and CESM respectively. LOAs for PathTotal varied from 60% under to a 2.4 or almost threefold over estimation. MRI was concordant with PathTotal in 36 (64%) cases compared with 32 (57%) for CESM. Both modalities concordant in 26 (46%) cases respectively. CONCLUSION: Neither CEM nor MRI have sufficient accuracy to direct changes in planned treatment without needle biopsy confirmation. ADVANCES IN KNOWLEDGE: Despite small mean differences in lesion size estimates using CEM or MRI, the 95% limits of agreement do not meet clinically acceptable levels.

Interpreting contrast imaging to plan breast surgery.

BACKGROUND: Contrast enhanced mammography (CEM) and magnetic resonance imaging (MRI) are more accurate than conventional imaging (CI) for breast cancer staging. How adding CEM and MRI to CI might change the surgical plan is understudied. METHODS: Surgical plans (breast conserving surgery (BCS), wider BCS, BCS with diagnostic excision (>1BCS), mastectomy) were devised by mock-MDT (radiologist, surgeon and pathology reports) according to disease extent on CI, CI + CEM and CI + MRI. Differences in the mock-MDT's surgical plans following the addition of CEM or MRI were investigated. Using pre-defined criteria, the appropriateness of the modified plans was assessed by comparing estimated disease extent on imaging with final pathology. Surgery performed was recorded from patient records. RESULTS: Contrast imaging modified mock-MDT plans for 20 of 61(32.8%) breasts. The addition of CEM changed the plan in 16/20 (80%) and MRI in 17/20 breasts (85%). Identical changes were proposed by both CEM and MRI in 13/20 (65%) breasts. The modified surgical plan based on CI + CEM was possibly appropriate for 6/16 (37.5%), and CI + MRI in 9/17, (52.9%) breasts. The surgery performed was concordant with the mock-MDT plan for all 10 patients where the plans could be compared (BCS 1, >1 BCS 2 and mastectomy 7). CONCLUSION: Adding CEM or MRI to CI changed mock-MDT plans in up to one third of women, but not all were appropriate. Changing surgical plans following addition of contrast imaging to CI without biopsy confirmation could lead to over or under-treatment.

Stress Hormones Epinephrine and Corticosterone Selectively Reactivate HSV-1 and HSV-2 in Sympathetic and Sensory Neurons.

Herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) establish latency in sensory and autonomic neurons, from which they can reactivate to cause recurrent disease throughout the life of the host. Stress is strongly associated with HSV recurrences in humans and animal models. However, the mechanisms through which stress hormones act on the latent virus to cause reactivation are unknown. We show that the stress hormones epinephrine (EPI) and corticosterone (CORT) induce HSV-1 reactivation selectively in sympathetic neurons, but not sensory or parasympathetic neurons. Activation of multiple adrenergic receptors is necessary for EPI-induced HSV-1 reactivation, while CORT requires the glucocorticoid receptor. In contrast, CORT, but not EPI, induces HSV-2 reactivation in both sensory and sympathetic neurons through either glucocorticoid or mineralocorticoid receptors. Reactivation is dependent on different transcription factors for EPI and CORT, and coincides with rapid changes in viral gene expression, although genes differ for HSV-1 and HSV-2, and temporal kinetics differ for EPI and CORT. Thus, stress-induced reactivation mechanisms are neuron-specific, stimulus-specific and virus-specific. These findings have implications for differences in HSV-1 and HSV-2 recurrent disease patterns and frequencies, as well as development of targeted, more effective antivirals that may act on different responses in different types of neurons.

A Global Review of Causes of Morbidity and Mortality in Free-Living Vultures.

Vulture species worldwide play a key role in ecosystems as obligate scavengers, and several populations have had precipitous declines. Research on vulture health is critical to conservation efforts including free-living vultures and captive breeding programs, but is limited to date. In this systematic review, we determined the reported causes of free-living vulture species morbidity and mortality worldwide. The most commonly reported cause of mortality was from toxins (60%), especially lead and pesticides, followed by traumatic injury (49%), including collisions with urban infrastructure and gunshot. Neglected areas of research in free-living vulture health include infectious diseases (16%), endocrine and nutritional disorders (6%), and neoplasia (< 1%). Almost half of the studies included in the review were conducted in either Spain or the USA, with a paucity of studies conducted in South America and sub-Saharan Africa. The highest number of studies was on Griffon (Gyps fulvus) (24%) and Egyptian vultures (Neophron percnopterus) (19%), while half of all vulture species had five or fewer studies. Future investigations on free-living vulture health should focus on neglected areas of research, such as infectious diseases, and areas with gaps in the current literature, such as South America, sub-Saharan Africa, and under-studied vulture species.