Coronary artery anomalies: assessment with free-breathing three-dimensional coronary MR angiography

PURPOSE: To evaluate a simplified protocol by using free-breathing three-dimensional (3D) coronary magnetic resonance (MR) angiography to determine the anatomy of anomalous coronary arteries, in particular the relationship of the vessels to the aortic root. MATERIALS AND METHODS: Twenty-six patients (18 men, eight women; mean age, 50 years; age range, 18-77 years) who had a history of chest pain, palpitations, or syncope and who were suspected of having coronary artery anomalies were examined with free-breathing MR angiography. Multiple 3D volume slabs were acquired at the level of the sinuses of Valsalva by using diaphragmatic navigators for respiratory artifact suppression. The proximal anatomy of the coronary arteries was determined. RESULTS: Six anomalous circumflex arteries originated from the right sinus of Valsalva and passed behind the aortic root. Six right coronary arteries arose from the left sinus of Valsalva and coursed between the aortic root and the right ventricular outflow tract (RVOT). Nine left coronary arteries arose from the right sinus of Valsalva; seven of nine coursed between the aortic root and the RVOT. Five patients had minor anomalies. Overall, in eight patients with anomalous arteries that coursed between the aortic root and the RVOT, conventional coronary angiography could not be used confidently to identify the proximal course. CONCLUSION: Free-breathing 3D coronary MR angiography can be used to identify the proximal anatomy of anomalous coronary arteries.     

High technology medicine and the physician-patient relationship

While technologic problems in critical care have become highly refined with precise solutions, ethical problems and solutions have remained fairly primitive. A useful distinction between technology and techniques is made with individual technologies being the parts that make up the therapeutic techniques as a whole. The phenomena of “technical convergence” is discussed wherein we may control each part of the system, but the system itself may be out of control. This is explained in terms of the logical fallacy of composition, noting that a whole may not necessarily have the same characteristics of its parts. Resolution of some of the ethical problems in critical care is suggested through a reexamination of the physician-patient relationship. It is noted that the relationship needs to be personal-technologic rather than sociotechnologic in nature, with the former focusing solely on the best interest of the individual patient and the latter focusing more on the broader concerns of society in the allocation of limited resources. The detrimental effects for the physician as well as the patient of the shift toward the sociotechnologic relationship is explored, especially the dehumanization of the physician. A call for a reaffirmation of the traditional professional model of medicine emphasizing the best interest of patients as opposed to the more popular business model emphasizing materialism and efficiency is given.     

PI3K inhibition to overcome endocrine resistance in breast cancer

Introduction: Activation of the phosphatidylinositol-3 kinase (PI3K) pathway is a critical step in oncogenesis and plays a role in the development of treatment resistance for both estrogen receptor (ER) positive and human epidermal growth factor receptor 2 (HER2) positive breast cancers. Hence, there have been efforts to therapeutically inhibit this pathway.

Areas covered: Several inhibitors of PI3K are now progressing through clinical trials with varying degrees of efficacy and toxicity to date. Numerous unresolved questions remain concerning the optimal isoform selectivity of PI3K inhibitors and use of predictive biomarkers. This review examines the most important PI3K inhibitors in ER positive breast cancer to date, with a particular focus on their role in overcoming endocrine therapy resistance and the possible use of PIK3CA mutations as a predictive biomarker.

Expert opinion: We discuss some of the emerging challenges and questions encountered during the development of PI3K inhibitors from preclinical to phase III studies, including other novel biomarkers and future combinations to overcome endocrine resistance.     

Racial/Ethnic and Socioeconomic Differences in Short-Term Breast Cancer Survival Among Women in an Integrated Health System

Objectives. We examined the combined influence of race/ethnicity and neighborhood socioeconomic status (SES) on short-term survival among women with uniform access to health care and treatment.Methods. Using electronic medical records data from Kaiser Permanente Northern California linked to data from the California Cancer Registry, we included 6262 women newly diagnosed with invasive breast cancer. We analyzed survival using multivariable Cox proportional hazards regression with follow-up through 2010.Results. After consideration of tumor stage, subtype, comorbidity, and type of treatment received, non-Hispanic White women living in low-SES neighborhoods (hazard ratio [HR] = 1.28; 95% confidence interval [CI] = 1.07, 1.52) and African Americans regardless of neighborhood SES (high SES: HR = 1.44; 95% CI = 1.01, 2.07; low SES: HR = 1.88; 95% CI = 1.42, 2.50) had worse overall survival than did non-Hispanic White women living in high-SES neighborhoods. Results were similar for breast cancer–specific survival, except that African Americans and non-Hispanic Whites living in high-SES neighborhoods had similar survival.Conclusions. Strategies to address the underlying factors that may influence treatment intensity and adherence, such as comorbidities and logistical barriers, should be targeted at low-SES non-Hispanic White and all African American patients.Breast cancer is the most common cancer among women in the United States, and it is the second leading cause of cancer death.1 Despite significant improvements in breast cancer survival from 1992 to 2009,1,2 racial/ethnic and socioeconomic survival disparities have persisted.3,4 African American women have consistently been found to have worse survival after breast cancer,3,5–11 Hispanic women have worse or similar survival,3,9,11,12 and Asian women as an aggregated group have better or similar survival3,9,11,12 than do non-Hispanic White women. Underlying factors thought to contribute to these racial/ethnic disparities include differences in stage at diagnosis,8,12,13 distributions of breast cancer subtypes,14–16 comorbidities,12,13,17 access to and utilization of quality care,13,18 and treatment.12,13Numerous studies also have found poorer survival after breast cancer diagnosis among women residing in neighborhoods of lower socioeconomic status (SES).6,9,19,20 Research has shown that inadequate use of cancer screening services, and consequent late stage diagnosis and decreased survival, contribute to the SES disparities.21,22 Similar to racial/ethnic disparities, SES disparities have been attributed to inadequate treatment and follow-up care and comorbidities.18 Previous population-based studies have continued to observe racial/ethnic survival disparities after adjusting for neighborhood SES, but these studies have not considered the combined influence of neighborhood SES and race/ethnicity.3,9,11,12,23 These disparities may remain because information on individual-level SES, health insurance coverage, comorbidities, quality of care, and detailed treatment regimens have typically not been available.3,8,9,11,13 Even among studies using national Surveillance Epidemiology and End Results–Medicare linked data, in which more detailed information on treatment and comorbidities are available among some patients aged 65 years and older, survival disparities have remained.12,23,24 However, not all data on medical conditions and health care services are captured in Medicare claims, including data on Medicare beneficiaries enrolled in HMOs (health maintenance organizations).25,26Using electronic medical records data from Kaiser Permanente Northern California (KPNC) linked to data from the population-based California Cancer Registry (CCR), we recently reported that chemotherapy use followed practice guidelines but varied by race/ethnicity and neighborhood SES in this integrated health system.27 Therefore, to overcome the limitations of previous studies and address simultaneously the multiple social28 and clinical factors affecting survival after breast cancer diagnosis, we used the linked KPNC–CCR database to determine whether racial/ethnic and socioeconomic differences in short-term overall and breast cancer–specific survival persist in women in a membership-based health system. Our study is the first, to our knowledge, to consider the combined influence of neighborhood SES and race/ethnicity and numerous prognostic factors, including breast cancer subtypes and comorbidities, thought to underlie these long-standing survival disparities among women with uniform access to health care and treatment.     

Coordinated Strategy for a Model-Based Decision Support Tool for Coronavirus Disease,Utah, USA

The coronavirus disease pandemic has highlighted the key role epidemiologic models play in supporting public health decision-making. In particular, these models provide estimates of outbreak potential when data are scarce and decision-making is critical and urgent. We document the integrated modeling response used in the US state of Utah early in the coronavirus disease pandemic, which brought together a diverse set of technical experts and public health and healthcare officials and led to an evidence-based response to the pandemic. We describe how we adapted a standard epidemiologic model; harmonized the outputs across modeling groups; and maintained a constant dialogue with policymakers at multiple levels of government to produce timely, evidence-based, and coordinated public health recommendations and interventions during the first wave of the pandemic. This framework continues to support the state’s response to ongoing outbreaks and can be applied in other settings to address unique public health challenges.     

Employment Hardships and Single Mothers’ Self-Rated Health: Evidence from the Panel Study of Income Dynamics

Using a national sample of single mothers from the 2007 and 2009 waves of the Panel Study of Income Dynamics, this study examined the effects of multiple employment statuses on the selfrated health of single mothers during the recent economic recession. Unlike other studies, the current study minimized selection bias by controlling for prior self-rated health, in addition to other predisposing factors, enabling factors, and need factors. We found that underemployment, but not unemployment, is associated with lower levels of self-rated health of single mothers. Results further indicate that the 25–39 age range (compared to the 18–24 age range), lower family income, prior lower self-rated health, more chronic diseases, and binge drinking place single mothers at an increased risk of lower levels of self-rated health. In contrast, strength-building physical activity is significantly associated with higher levels of self-rated health. Implications for health care policy and social work practice are drawn from the results.     

1,4-Benzodiazepines as inhibitors of respiratory syncytial virus

Respiratory syncytial virus (RSV) is the cause of one-fifth of all lower respiratory tract infections worldwide and is increasingly being recognized as a serious threat to patient groups with poorly functioning immune systems. Our approach to finding a novel inhibitor of this virus was to screen a 20 000-member diverse library in a whole cell XTT assay. Parallel assays were carried out in the absence of virus in order to quantify any associated cell toxicity. This identified 100 compounds with IC(50)'s less than 50 muM. A-33903 (18), a 1,4-benzodiazepine analogue, was chosen as the starting point for lead optimization. This molecule was moderately active and demonstrated good pharmacokinetic properties. The most potent compounds identified from this work were A-58568 (47), A-58569 (44), and A-62066 (46), where modifications to the aromatic substitution enhanced potency, and A-58175 (42), where the amide linker was modified.