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Background There is limited data on electrocardiographic (ECG) abnormalities and their prognostic significance in women with peripartum cardiomyopathy (PPCM). We sought to characterize ECG findings in PPCM and explore the association of ECG findings with myocardial recovery and clinical outcomes. Hypothesis We hypothesized that ECG indicators of myocardial remodeling would portend worse systolic function and outcomes. Methods Standard 12‐lead ECGs were obtained at enrollment in the Investigations of Pregnancy‐Associated Cardiomyopathy study and analyzed for 88 women. Left ventricular ejection fraction (LVEF) was measured by echocardiography at baseline, 6 months, and 12 months. Women were followed for clinical events (death, mechanical circulatory support, and/or cardiac transplantation) until 1 year. Results Half of women had an “abnormal” ECG, defined as atrial abnormality, ventricular hypertrophy, ST‐segment deviation, and/or bundle branch block. Women with left atrial abnormality (LAA) had lower LVEF at 6 months (44% vs 52%, P = 0.02) and 12 months (46% vs 54%, P = 0.03). LAA also predicted decreased event‐free survival at 1 year (76% vs 97%, P = 0.008). Neither left ventricular hypertrophy by ECG nor T‐wave abnormalities predicted outcomes. A normal ECG was associated with recovery in LVEF to ≥50% (84% vs 49%, P = 0.001) and event‐free survival at 1 year (100% vs 85%, P = 0.01). Conclusions ECG abnormalities are common in women with PPCM, but a normal ECG does not rule out the presence of PPCM. LAA predicted lower likelihood of myocardial recovery and event‐free survival, and a normal ECG predicted favorable event‐free survival.

Some prior evidence suggests that adverse pregnancy outcomes (APOs) may be associated with heart failure (HF). Identifying unique factors associated with the risk of HF and studying HF subtypes are important next steps. To investigate the association of APOs with incident HF overall and stratified by HF subtype (preserved vs reduced ejection fraction) among postmenopausal women in the Women's Health Initiative (WHI). In 2017, an APO history survey was administered in the WHI study, a large multiethnic cohort of postmenopausal women. The associations of 5 APOs (gestational diabetes, hypertensive disorders of pregnancy [HDP], low birth weight, high birth weight, and preterm delivery) with incident adjudicated HF were analyzed. In this cohort study, the association of each APO with HF was assessed using logistic regression models and with HF subtypes using multinomial regression, adjusting for age, sociodemographic characteristics, smoking, randomization status, reproductive history, and other APOs. Data analysis was performed from January 2020 to September 2021. APOs (gestational diabetes, HDP, low birth weight, high birth weight, and preterm delivery). All confirmed cases of women hospitalized with HF and HF subtype were adjudicated by trained physicians using standardized methods. Of 10 292 women (median [IQR] age, 60 [55-64] years), 3185 (31.0%) reported 1 or more APO and 336 (3.3%) had a diagnosis of HF. Women with a history of any APO had a higher prevalence of hypertension, diabetes, coronary heart disease, or smoking. Of the APOs studied, only HDP was significantly associated with HF with a fully adjusted odds ratio (OR) of 1.75 (95% CI, 1.22-2.50), and with HF with preserved ejection fraction in fully adjusted models (OR, 2.06; 95% CI, 1.29-3.27). In mediation analyses, hypertension explained 24% (95% CI, 12%-73%), coronary heart disease 23% (95% CI, 11%-68%), and body mass index 20% (95% CI, 10%-64%) of the association between HDP and HF. In this large cohort of postmenopausal women, HDP was independently associated with incident HF, particularly HF with preserved ejection fraction, and this association was mediated by subsequent hypertension, coronary heart disease, and obesity. These findings suggest that monitoring and modifying these factors early in women presenting with HDP may be associated with reduced long-term risk of HF.

Trastuzumab is a monoclonal antibody highly effective in the treatment of several cancers, but its use is associated with cardiac toxicity which usually responds to cessation of the drug and/or medical therapy. We present an unusual case of acute cardiac toxicity temporally related to administration of trastuzumab in which the clinical presentation suggested an acute coronary syndrome. Coronary angiography, however, demonstrated minimal epicardial disease, but new wall motion abnormalities. Furthermore, the patient did not respond to withdrawal of the drug or medical therapy for heart failure.

Introduction Cardio‐oncology focuses on diagnosing and preventing adverse cardiovascular outcomes in cancer patients. Interdisciplinary cardio‐oncology services address the spectrum of prevention, detection, monitoring, and treatment of cancer patients at risk of cardio‐toxicity and aim to improve the continuum of cardiac care for oncology patients. The goal of this study was to engage clinician and administrative stakeholders to assess multilevel needs, barriers, and expectations regarding cardio oncology services. Methods We interviewed clinicians and administrators at an academic medical center using the Consolidated Framework for Implementation Research (CFIR) to understand multilevel determinants influencing cardio‐oncology service implementation. We also conducted a web‐based survey to assess the knowledge, attitude, and perceptions of cardio‐oncology services held by local and regional clinicians who may refer cardio‐oncology patients to the study site. Results Multiple facilitators to cardio‐oncology service implementation emerged. Interview participants believed cardio‐oncology services could benefit patients and the organization by providing a competitive advantage. A majority (74%) of clinicians surveyed thought a cardio‐oncology service would significantly improve cancer patients’ prognoses. Implementation barriers discussed included costs and a siloed organizational structure that complicated cross‐service collaboration. In the clinician survey, differences in the views toward cardio‐oncology services held by cardiology versus oncology providers would need to be negotiated in future cardio‐oncology service development. For example, while most providers accepted similar risk of cardio‐toxicity when consenting patients for cancer therapy in a curative setting, cardiologists accepted significantly higher levels of risk than oncologists in an incurable setting: 75% of oncologists accepted 1‐5% risk; 77% of cardiologists accepted ≥5% risk). Conclusions Participants supported implementation and development of cardio‐oncology services. Respondents also noted multi‐level barriers that could be addressed to maximize the potential for success. Engaging administrators and clinicians from cardiology and oncology disciplines in the future development of such services can help ensure maximal relevance and uptake.

Background Cardiovascular health (CVH) has been defined by the American Heart Association (AHA) as the presence of the “Life’s Simple 7” ideal lifestyle and clinical factors. CVH is known to predict longevity and freedom from cardiovascular disease, the leading cause of death for women in the United States. DNA methylation markers of aging have been aggregated into a composite epigenetic age score, which is associated with cardiovascular morbidity and mortality. However, it is unknown whether poor CVH is associated with acceleration of aging as measured by DNA methylation markers in epigenetic age. Methods and results We performed a cross-sectional analysis of racially/ethnically diverse post-menopausal women enrolled in the Women’s Health Initiative cohort recruited between 1993 and 1998. Epigenetic age acceleration (EAA) was calculated using DNA methylation data on a subset of participants and the published Horvath and Hannum methods for intrinsic and extrinsic EAA. CVH was calculated using the AHA measures of CVH contributing to a 7-point score. We examined the association between CVH score and EAA using linear regression modeling adjusting for self-reported race/ethnicity and education. Among the 2,170 participants analyzed, 50% were white and mean age was 64 (7 SD) years. Higher or more favorable CVH scores were associated with lower extrinsic EAA (~ 6 months younger age per 1 point higher CVH score, p  < 0.0001), and lower intrinsic EAA (3 months younger age per 1 point higher CVH score, p  < 0.028). Conclusions These cross-sectional observations suggest a possible mechanism by which ideal CVH is associated with greater longevity.

While biomarkers have been proposed to identify individuals at risk for radiation-induced cardiovascular disease (RICVD), little is known about long-term associations with cardiac events. We examined associations of biomarkers of oxidative stress (myeloperoxidase, growth differentiation factor-15, 8-hydroxy-2′-deoxyguanosine [8-OH-dG], placental growth factor), cardiac injury (troponin I, cystatin-C), inflammation (interleukin-6, C-reactive protein), and myocardial fibrosis (transforming growth factor-ß) with long-term RICVD in breast cancer (BC) survivors. We conducted a nested case–control study within the Women’s Health Initiative of postmenopausal women with incident BC stages I–III, who received radiation and had pre- and post-BC diagnosis serum samples. Cases ( n  = 55) were defined as developing incident, physician-adjudicated myocardial infarction, coronary heart disease death, other CVD death, heart failure, or stroke after BC. Cases were matched to three controls ( n  = 158). After adjustment, a higher 8-OH-dG ratio was significantly associated with an elevated long-term risk of RICVD, suggesting oxidative DNA damage may be a putative pathway for RICVD. Graphical abstract

Couples with repeated pregnancy wastage are often referred for cytogenetics studies to exclude a chromosomal aberration as the etiology of their reproductive loss. In approximately 5% of these couples, one member will have a chromosome rearrangement (either a translocation or an inversion). Some investigators have reported a higher incidence of sex chromosome aneuploidy, especially in women with recurrent spontaneous abortions. Among women with repeated pregnancy wastage, the presence of one or a few X chromosome aneuploid cells is a fairly common laboratory finding. To determine the clinical significance of the occasional X aneuploid cell, a study was initiated comparing 49 women with two or more spontaneous abortions (experimental group) with 49 age-matched women with healthy children and no miscarriages (control group). Thirty G-banded metaphase cells from cultured lymphocytes were examined for each subject and low levels of sex chromosome aneuploidy were recorded for both groups. The predominant chromosomal pattern was 46,XX with an occasional cell having either 45,X or 47,XXX. Neither the total number of women with sex chromosome mosaicism nor the number of cells with extra or missing chromosomes was significantly different between the two groups ($\\alpha$ = 0.05).

A large ex vivo screen of approved and investigational anti-cancer drugs in primary cells derived from CML and ALL patients identifies axitinib, a VEGFR inhibitor approved for the treatment of kidney cancer, as a potent inhibitor of BCR–ABL1(T315I) with unique binding interactions that overcome the gatekeeper resistance mutation, highlighting the potential of repurposing existing drugs for additional cancer types. Anti-leukaemia potential of axitinib Many chronic myeloid leukaemias (CMLs) and acute lymphoblastic leukaemias (ALLs) are driven by the BCR-ABL fusion gene. Targeting BCR-ABL with selective kinase inhibitors has revolutionized CML treatment, but patients often develop resistance, often due to secondary mutations in BCR-ABL . In this large-scale screen of approved and investigational anti-cancer drugs in primary cells from CML and ALL patients, Krister Wennerberg and colleagues identify axitinib, a multi-kinase inhibitor approved for the treatment of kidney cancer, as having activity in primary patient-derived CML and ALL cells, including cells with secondary resistance mutations. In one CML patient, for whom all other treatment options had been exhausted, axitinib induced reduced levels of circulating BCR - ABL transcripts. These preliminary clinical findings highlight the potential of repurposing existing drugs for additional cancer types. The BCR-ABL1 fusion gene is a driver oncogene in chronic myeloid leukaemia and 30–50% of cases of adult acute lymphoblastic leukaemia 1 . Introduction of ABL1 kinase inhibitors (for example, imatinib) has markedly improved patient survival 2 , but acquired drug resistance remains a challenge 3 , 4 , 5 . Point mutations in the ABL1 kinase domain weaken inhibitor binding 6 and represent the most common clinical resistance mechanism. The BCR–ABL1 kinase domain gatekeeper mutation Thr315Ile (T315I) confers resistance to all approved ABL1 inhibitors except ponatinib 7 , 8 , which has toxicity limitations. Here we combine comprehensive drug sensitivity and resistance profiling of patient cells ex vivo with structural analysis to establish the VEGFR tyrosine kinase inhibitor axitinib as a selective and effective inhibitor for T315I-mutant BCR–ABL1-driven leukaemia. Axitinib potently inhibited BCR–ABL1(T315I), at both biochemical and cellular levels, by binding to the active form of ABL1(T315I) in a mutation-selective binding mode. These findings suggest that the T315I mutation shifts the conformational equilibrium of the kinase in favour of an active (DFG-in) A-loop conformation, which has more optimal binding interactions with axitinib. Treatment of a T315I chronic myeloid leukaemia patient with axitinib resulted in a rapid reduction of T315I-positive cells from bone marrow. Taken together, our findings demonstrate an unexpected opportunity to repurpose axitinib, an anti-angiogenic drug approved for renal cancer, as an inhibitor for ABL1 gatekeeper mutant drug-resistant leukaemia patients. This study shows that wild-type proteins do not always sample the conformations available to disease-relevant mutant proteins and that comprehensive drug testing of patient-derived cells can identify unpredictable, clinically significant drug-repositioning opportunities.

Studies of the resident community of bottlenose dolphins ( Tursiops truncatus ) of Sarasota Bay, Florida, have been conducted for more than 50 years. Detailed histories have been collected for resident individuals through integrated observations, systematic photographic identification surveys, tagging and tracking, catch-and-release health assessments, remote biopsy sampling, and stranding response. This has produced a unique dataset documenting life history milestones and vital rates of a small cetacean. Analyses of data from 482 resident Sarasota Bay dolphins have revealed estimated maximum life spans of 67 years for females and 52 years for males. For females, predicted age at sexual maturation is 8.5 years, with a predicted age at first reproduction of 9.6 years. Females were observed to give birth when 6-48 years of age, and have been documented with as many as 12 calves, with 45% observed post-separation. Ten percent of females were considered to be reproductively senescent, having gone >13 years without producing a calf. For males, predicted age at sexual maturation is 10 years. Males 10-43 years old sired calves, producing up to 7 calves each. The average calving interval was 3.5 years, albeit with effects due to mother’s age, birth order, and calf survival. Seasonal reproduction was evident, with 81% of births occurring during May-July. Mean annual birth rate was 0.071. Mean annual fecundity was 0.182 births/adult female (defined as females 6 yrs or older). Recruitment rate through reproduction was estimated to be 0.050 based on calves surviving their first year. Immigration was infrequent, with an estimated annual rate of 0.003-0.013. Estimated mean annual maximum loss rate, from mortality, emigration, and changed identification characteristics, was 0.072. Periods of increased loss rates were related to environmental events, and factors that may be important to long-term population resilience were suggested.

This study addresses the gap in research on the educational experiences of adolescent human trafficking survivors, with a focus on their past, present, and future educational experiences and goals. Its objective is to inform the best practices for educational programming within female adolescent residential care centers in the United States. Drawing on a subset of data from a broader mixed-methods case study conducted at the Allasso House residential facility, this research involved 11 current residents. The data sources included case files detailing their past educational experiences, assessments of their current educational achievements, and interviews exploring their future aspirations. The findings reveal key themes related to the residents past risk factors, current educational successes and barriers, and tensions in setting future goals. Most of the residents expressed a desire to attain high school equivalency, identifying financial stability as a primary motivation. They also aspired to form healthy families, while placing significant value on material success. Unlike studies that define success primarily through survival, sobriety, and the avoidance of re-trafficking, this research highlights the broader aspirations of these adolescents, emphasizing the critical role of education in general wellbeing, risk mitigation, and future success. This study underscores the importance of prioritizing educational attainment and long-term aspirations in future research and in the design of residential programs for adolescent survivors of trafficking.