Publications

BACKGROUND AND OBJECTIVES

Breast milk is a complex bioactive fluid that varies across numerous maternal and environmental conditions. Although breast-feeding is known to affect neonatal gut microbiome, the milk components responsible for this effect are not well-characterized. Given the wide range of immunological activity breast milk cytokines engage in, we investigated 3 essential breast milk cytokines and their association with early life gut microbiota.

METHODS

A total of 52 maternal-child pairs were drawn from a racially diverse birth cohort based in Detroit, Michigan. Breast milk and neonatal stool specimens were collected at 1-month postpartum. Breast milk transforming growth factor (TGF)β1, TGFβ2, and IL-10 were assayed using enzyme-linked immunosorbent assays, whereas neonatal gut microbiome was profiled using 16S rRNA sequencing.

RESULTS

Individually, immunomodulators TGFβ1 and TGFβ2 were significantly associated with neonatal gut microbial composition (R = 0.024, P = 0.041; R = 0.026, P = 0.012, respectively) and increased richness, evenness, and diversity, but IL-10 was not. The effects of TGFβ1 and TGFβ2, however, were not independent of one another, and the effect of TGFβ2 was stronger than that of TGFβ1. Higher levels of TGFβ2 were associated with the increased relative abundance of several bacteria, including members of Streptococcaceae and Ruminococcaceae, and lower relative abundance of distinct Staphylococcaceae taxa.

CONCLUSIONS

Breast milk TGFβ concentration explains a portion of variability in gut bacterial microbiota composition among breast-fed neonates. Whether TGFβ acts in isolation or jointly with other bioactive components to alter bacterial composition requires further investigation. These findings contribute to an increased understanding of how breast-feeding affects the gut microbiome-and potentially immune development-in early life.

BACKGROUND

The prevalence of atrial fibrillation in the HIV-infected population is growing, but the ability of the CHA2DS2-VASc score to predict thromboembolic (TE) risk is unknown in this population.

SETTING

Within the Veterans Affairs HIV Clinical Case Registry, 914 patients had an atrial fibrillation diagnosis between 1997 and 2011 and no previous TE events.

METHODS

We compared TE incidence by CHA2DS2-VASc scores and stratified by warfarin use. Using Cox proportional hazards regression with adjustment for competing risks, we modeled associations of CHA2DS2-VASc scores and warfarin use with TE risk.

RESULTS

At baseline, the distribution of CHA2DS2-VASc scores was 0 (n = 208), 1 (n = 285), and 2+ (n = 421); 34 patients developed 38 TE events during a median of 3.8 years follow-up. Event rates by CHA2DS2-VASc scores of 0, 1, and 2+ were 5.4, 9.3, and 8.1 per 1000 person years, respectively; multivariate-adjusted hazards ratios (HRs) were 1.70 (95% confidence interval: 0.65 to 4.45) for CHA2DS2-VASc score 1 (P = 0.28) and HR = 1.34 (0.51, 3.48) for score 2+ versus 0 (P = 0.55). Baseline warfarin use was associated with increased TE risk, although not statistically significant [HR 2.06 (0.86, 4.93), P = 0.11] with similar results when modeled as time-updated use and duration of use.

CONCLUSION

In this national registry of HIV-infected veterans with atrial fibrillation, CHA2DS2-VASc scores were only weakly associated with TE risk. Furthermore, warfarin did not seem to be effective at preventing TE events. These results should raise concerns about the optimal strategy for TE prevention among HIV-infected persons with atrial fibrillation.

Background

Osteopetrosis encompasses a group of rare metabolic bone diseases characterized by impaired osteoclast activity or development, resulting in high bone mineral density. Existing guidelines focus on treatment of the severe infantile forms with hematopoietic cell transplantation (HCT) but do not address the management of patients with less severe forms for whom HCT is not the standard of care. Therefore, our objective was to develop expert consensus guidelines for the management of these patients.

Methods

A modified Delphi method was used to build consensus among participants of the Osteopetrosis Working Group, with responses to an anonymous online survey used to identify areas of agreement and conflict and develop a follow-up survey. The strength of recommendations and quality of evidence was graded using the Grading of Recommendations Assessment, Development and Evaluation system.

Results

Consensus was found in the areas of diagnosis, monitoring, and treatment. We recommend relying on characteristic radiographic findings to make the diagnosis and found that genetic testing adds important information by identifying mutations associated with unique disease complications. We recommend ongoing monitoring for changes in mineral metabolism and other complications, including cranial nerve impingement, anemia, leukopenia, and dental disease. We suggest that calcitriol should not be used in high doses and instead recommend symptom-based supportive therapy for disease complications because noninfantile osteopetrosis has no effective treatment.

Conclusions

Scarcity of published studies on osteopetrosis reduce the ability to develop evidence-based guidelines for the management of these patients. Expert opinion-based guidelines for this rare condition are nevertheless important to enable improved care.

BACKGROUND

Adequate antiretroviral exposure is crucial to virological suppression. We assessed the relationship between atazanavir hair levels with self-reported adherence, virological outcomes, and the effect of a home-based adherence intervention in HIV-infected adolescents failing second-line antiretroviral treatment in Zimbabwe.

METHODS

HIV-infected adolescents on atazanavir/ritonavir-based second-line treatment for ≥6 months with viral load (VL) >1000 copies/mL were randomized to either standard care (control) or standard care plus modified directly administered antiretroviral therapy (intervention). Questionnaires were administered; VL and hair samples were collected at baseline and after 90 days in each group. Viral suppression was defined as <1000 copies/mL after follow-up.

RESULTS

Fifty adolescents (10-18 years) were enrolled; 23 (46%) were randomized to intervention and 27 (54%) to control. Atazanavir hair concentration <2.35 ng/mg (lower interquartile range for those with virological suppression) defined a cutoff below which most participants experienced virological failure. Male sex (P = 0.03), virological suppression at follow-up (P = 0.013), greater reduction in VL (P = 0.006), and change in average self-reported adherence over the previous month (P = 0.031) were associated with adequate (>2.35 ng/mg) hair concentrations. Participants with virological failure were more likely to have suboptimal atazanavir hair concentrations (RR = 7.2, 95% CI: 1 to 51, P = 0.049). There were no differences in atazanavir hair concentration between the arms after follow-up.

CONCLUSIONS

A threshold of atazanavir concentrations in hair (2.35 ng/mg), above which virological suppression was likely, was defined for adolescents failing second-line atazanavir/ritonavir-based ART in Zimbabwe. Male sex and better self-reported adherence were associated with adequate atazanavir hair concentrations. Antiretroviral hair concentrations may serve as a useful clinical tool among adolescents.

Cancer disparities research is motivated by persistent inequities in cancer outcomes by race, ethnicity, social status, neighborhood location, and other subpopulation characteristics. These inequities have proven to be persistent and difficult to alter. Part of the reason for the frustration with slow progress is a lack of appreciation of the long-term nature of the undertaking. It is highly likely that the disparities observed in adulthood find their origins in young adulthood, if not earlier. A long-term perspective is needed, recognizing that successes may take many years to realize. This commentary presents the experience of the Center for Health And Risk in Minority youth and young adults project, which is a comprehensive center of excellence funded by the National Institute of Minority Health and Health Disparities for addressing disparities and chronic disease prevention in minority youth and young adults. The use of logic models is advanced for this kind of research because they can provide a theory of change and illustrate the course of knowledge translation over time. Logic models for cancer disparities research can place individual project activities in a realistic context that at one time indicates what is possible and reasonable to expect during the duration of a typical research project as well as the future steps that need to be taken on the way to an expected ultimate impact on cancer inequities.

BACKGROUND

Adipose fat transfer is increasingly used for contour corrections of the tumor bed after lumpectomy and breast reconstructions after mastectomy. The lipophilic nature of the fat tissue may render adipocytes an ideal vehicle with which to deliver a high boost of an antiestrogen to the tumor bed to serve as an adjunct systemic hormonal therapy. The authors therefore tested whether adipocytes could safely be loaded with an antiestrogen and allow for release at therapeutic concentrations to treat breast cancer.

METHODS

Adipose tissue was collected from patients undergoing autologous fat grafting. The influence of adipose tissue on tumorigenesis was determined both in vitro and in vivo using breast cancer cell lines. Ex vivo, adipose tissue was assessed for its ability to depot fulvestrant and inhibit the growth of breast cancer cell lines.

RESULTS

Adipose tissue harvested from patients did not promote breast cancer cell growth in vitro or in an in vivo mouse model. Adipose tissue was successfully loaded with fulvestrant and released at levels sufficient to inhibit estrogen receptor signaling and growth of breast cancer cells.

CONCLUSIONS

This work supports the hypothesis that adipose tissue used for autologous fat grafting can serve as a novel method for local drug delivery. As this technique is used to reconstruct a variety of postsurgical defects following cancer resection, this approach for local drug delivery may be an effective alternative in therapeutic settings beyond breast cancer.

Advance care planning (ACP) is increasingly implemented in oncology and beyond, but a definition of ACP and recommendations concerning its use are lacking. We used a formal Delphi consensus process to help develop a definition of ACP and provide recommendations for its application. Of the 109 experts (82 from Europe, 16 from North America, and 11 from Australia) who rated the ACP definitions and its 41 recommendations, agreement for each definition or recommendation was between 68-100%. ACP was defined as the ability to enable individuals to define goals and preferences for future medical treatment and care, to discuss these goals and preferences with family and health-care providers, and to record and review these preferences if appropriate. Recommendations included the adaptation of ACP based on the readiness of the individual; targeting ACP content as the individual's health condition worsens; and, using trained non-physician facilitators to support the ACP process. We present a list of outcome measures to enable the pooling and comparison of results of ACP studies. We believe that our recommendations can provide guidance for clinical practice, ACP policy, and research.

Importance

Poor communication by health care professionals contributes to physical and psychological suffering in patients living with serious illness. Patients may not fully understand their illness, prognosis, and treatment options or may not receive medical care consistent with their goals. Despite considerable research exploring the role of communication in this setting, many questions remain, and a clear agenda for communication research is lacking.

Observations

Through a consensus conference and subsequent activities, we reviewed the state of the science, identified key evidence gaps in understanding the impact of communication on patient outcomes, and created an agenda for future research. We considered 7 broad topics: shared decision making, advance care planning, communication training, measuring communication, communication about prognosis, emotion and serious illness communication, and cultural issues. We identified 5 areas in which further research could substantially move the field forward and help enhance patient care: measurement and methodology, including how to determine communication quality; mechanisms of communication, such as identifying the specific clinician behaviors that patients experience as both honest and compassionate, or the role of bias in the clinical encounter; alternative approaches to advance care planning that focus on the quality of serious illness communication and not simply completion of forms; teaching and disseminating communication skills; and approaches, such as economic incentives and other clinician motivators, to change communication behavior.

Conclusions

Our findings highlight the urgent need to improve quality of communication between health care professionals and patients living with serious illness through a broad range of research that covers communication skills, tools, patient education, and models of care.