While several prognostic factors have been identified in breast carcinoma, the clinical outcome remains hard to predict for individual patients. Better predictive markers are needed to help guide difficult treatment decisions. In a previous study of 78 breast carcinoma specimens, we noted an association between poor clinical outcome and the expression of cytokeratin 17 and/or cytokeratin 5 mRNAs. Here we describe the results of immunohistochemistry studies using monoclonal antibodies against these markers to analyze more than 600 paraffin-embedded breast tumors in tissue microarrays. We found that expression of cytokeratin 17 and/or cytokeratin 5/6 in tumor cells was associated with a poor clinical outcome. Moreover, multivariate analysis showed that in node-negative breast carcinoma, expression of these cytokeratins was a prognostic factor independent of tumor size and tumor grade.

The purpose of this paper is to present results from methodologies used in our laboratory that are targeted toward identifying specific brain injury thresholds. Results from studying one form of brain injury, diffuse axonal injury, are presented in this report. Physical models, or surrogates, of the skull-brain complex are used to estimate the relationship between inertial loading and brain deformation. A porcine model of diffuse axonal injury, developed with information from these physical models and earlier in vitro tissue modeling studies, is used to correlate histologic and radiologic evidence of axonal injury to predicted regions of injury from the experimental and theoretical analysis. These results form the basis for developing improved diffuse brain injury tolerance levels, as well as identifying new means of diagnostic and treatment techniques for diffuse axonal injury.

Short sleep duration in the natural environment may negatively affect in vivo antibody responses to novel antigens, providing a possible explanation for observed associations of poor sleep with increased susceptibility to infectious disease.

Laboratory studies show that individuals differ appreciably in the magnitude of their inflammatory responses to acute psychological stress. These individual differences are poorly understood, yet may contribute to variation in stress-associated disease vulnerability. The present study examined the possibility that affective responses to acute stress contribute to these differences. For this purpose, 102 relatively-healthy community volunteers (mean age 50 years; 60% female; 91.2% white) performed an acute stress protocol and measures of affective state and serum levels of the proinflammatory cytokine, interleukin (IL)-6 were collected at the end of a 30-min resting baseline, a 5-min evaluative public speaking task, and a 30-min recovery period. Results of regression analyses, controlling for age, race, gender, menopausal status, and body mass index, revealed a positive association of task-related increases in anger and anxiety with increases in IL-6 (R 2 change = .08, p = .004; R 2 change = .08, p = .005, respectively). Further examination showed that these affective responses to the task were independent predictors of change in IL-6. Cardiovascular reactivity to the task did not explain the association. These results suggest that individuals who exhibit angry or anxious responses to acute challenge are more vulnerable to stress-related increases in markers of systemic inflammation, possibly rendering them more susceptible to inflammatory disease.

Key Points Question Are concerns about the opioid epidemic in the United States and the heightened oversight and restrictions on prescribing opioids associated with changes in the management of acute and chronic pain for patients with sickle cell disease? Findings This qualitative study interviewed 15 adults with sickle cell disease. Participants reported that they face increased barriers to the use of opioids for pain management, that their physicians exclusively focus on opioid dosage without establishing a multimodality pain management plan, and that they lack access to nonopioid therapies. Meaning Adult patients with sickle cell disease should be included in establishing goals for managing pain and improving functionality using multimodality approaches.

Emerging evidence suggests that acute psychological stress modulates inflammatory competence; however, not all findings are consistent. Gender is one factor that may impact magnitude of response. To explore this possibility, we examined the effects of acute mental stress on lipopolysaccharideinduced production of pro-inflammatory cytokines interleukin (IL)-1 β, IL-6, and tumor necrosis factor (TNF)-α among a relatively healthy sample of midlife men (n=28) and women (n=34). Blood samples for the assessment of cytokine production were drawn before, immediately after and 30 minutes following subjects' performance of an evaluative speech task. Relative to baseline evaluations, the speech stressor elicited a significant increase in stimulated production of all 3 proinflammatory cytokines, as measured 30 minutes following the end of the task. There were no gender differences in the magnitude of this effect. However, men showed a significant decrease in cytokine production from before to immediately following the stressor, whereas women showed no change across this period. Menopausal status partially accounted for these gender differences, with postmenopausal women displaying greater increases in IL-6 and TNF-α production from baselineto-post task when compared to men. These data provide further evidence that acute psychological stress primes the immune system to mount larger inflammatory responses and initial support for gender differences in the patterning of stress-related cytokine activity. In addition, this study presents novel evidence that post-menopausal women may be particularly susceptible to stress-related inflammatory responses. The possibility that this contributes to the increased risk of inflammatory disease observed among older women warrants investigation.

The longitudinal collection of pain data with the inclusion of hospital data during periods of hospitalization is feasible and acceptable in patients with SCD over periods of 30 to 60 days. Long-term collection of pain diary data, while informative, is associated with higher rates of missing data. Novel metrics of pain have the potential to better describe intraindividual and interindividual variation in pain, inform studies of the transition from acute to chronic pain as well as contribute patient-reported end points of pain for interventional clinical trials of pain in SCD.

Sickle cell disease (SCD) is an inherited blood disorder that primarily affects African-American and other ethnic minority populations. There are three available disease-modifying therapies for sickle cell disease: hydroxyurea (HU), bone marrow transplantation (BMT), and chronic blood transfusion (CBT). Since these treatments vary in their therapeutic intent, efficacy in preventing progression of the disease, short and long-term adverse effects, costs and patient burden, the decision-making process regarding these therapies is complicated for both the patient and healthcare provider. While previous research has focused on the patient perspective of treatment-related decision making, there is a paucity of research investigating the physician perspective of treatment-related decision making. We conducted a qualitative study with physicians who were experts in the field of SCD. Interviews focused on physician perceptions of patient decisional needs as well as physicians’ approach to decision making regarding disease-modifying therapies in SCD. Thirty-six physician interviews were analyzed, with a focus on their perspectives regarding available treatment options and on how they approach decision making with patients. We identified two narrative approaches. The Collaborative approach (CA) was characterized by emphasizing the need to discuss all possible treatment options to ensure that the patient and/or family was equipped to make an informed decision. The Proponent approach (PA) was characterized by strongly advocating a pre-determined treatment plan and providing patients/families with information, with the objective of convincing them to accept the treatment. An interplay of patient-related and disease-related factors, decision type and physician-related factors, as well as institutional frameworks, influenced physician perspectives on treatment options and decision making regarding these therapies. These findings point to the potential value of developing systems to foster patient engagement as a way of facilitating shared decision making.