Citations

BackgroundCommunication failures between clinicians and dermatopathologists are prevalent. Our primary objective was to characterize the concerns and challenges of dermatopathologists posed by incomplete or inaccurate clinical information in the skin biopsy requisition form.MethodsAn explanatory sequential, mixed‐methods study design comprised of a survey sent to 1103 members of the American Society of Dermatopathology (ASDP), followed by two focus group sessions.ResultsA total of 54% (598/1103) of dermatopathologists completed the questionnaire. Most dermatopathologists (80%; 436/548) viewed their roles to be providers of histopathological diagnosis and a report that is clinically meaningful. Paper or electronic requisition forms were the most common communication method (85%; 458/541) and were associated with the highest rates of dissatisfaction in 36% (193/537) of respondents. Inadequacy of specimens emerged as an important factor influencing judgment of the quality of provided clinical information. 44.7% (261/584) of dermatopathologists spent 30 minutes or more on average every day searching for relevant clinical information to assist with their histopathologic interpretation.ConclusionASDP dermatopathologists expressed significant dissatisfaction with the quality of clinical information in the requisition form and the time spent gathering information necessary for accurate, timely and clinically meaningful diagnosis. These findings have implications for the quality, safety and efficiency of dermatologic care.

Purpose Legislation mandating disclosure of breast density (BD) information has passed in 21 states; however, actual awareness of BD and knowledge of its impact on breast cancer detection and risk are unknown. Methods We conducted a national cross-sectional survey administered in English and Spanish using a probability-based sample of screening-age women, with oversampling of Connecticut, the only state with BD legislation in effect for > 1 year before the survey. Results Of 2,311 women surveyed, 65% responded. Overall, 58% of women had heard of BD, 49% knew that BD affects breast cancer detection, and 53% knew that BD affects cancer risk. After multivariable adjustment, increased BD awareness was associated with white non-Hispanic race/ethnicity (Hispanic v white non-Hispanic: odds ratio [OR], 0.23; P < .001), household income (OR, 1.07 per category increase; P < .001), education (OR, 1.19 per category increase; P < .001), diagnostic evaluation after a mammogram (OR, 2.64; P < .001), and postmenopausal hormone therapy (OR, 1.69; P = .002). Knowledge of the masking effect of BD was associated with higher household income (OR, 1.10; P < .001), education (OR, 1.22; P = .01), prior breast biopsy (OR, 2.16; P < .001), and residing in Connecticut (Connecticut v other states: OR, 3.82; P = .003). Connecticut residents were also more likely to have discussed their BD with a health care provider (67% v 43% for residents of other US states; P = .001). Conclusion Disparities in BD awareness and knowledge exist by race/ethnicity, education, and income. BD legislation seems to be effective in increasing knowledge of BD impact on breast cancer detection. These findings support continued and targeted efforts to improve BD awareness and knowledge among women eligible for screening mammography.

Abstract Purpose: To evaluate safety (primary endpoint), tolerability, pharmacokinetics, pharmacodynamic profile, and preliminary activity of the intravenous, pan-class I isoform PI3K/mTOR inhibitor PF-05212384 in patients with advanced solid tumors. Experimental Design: Part 1 of this open-label phase I study was designed to estimate the maximum-tolerated dose (MTD) in patients with nonselected solid tumors, using a modified continual reassessment method to guide dose escalation. Objectives of part 2 were MTD confirmation and assessment of preliminary activity in patients with selected tumor types and PI3K pathway dysregulation. Results: Seventy-seven of the 78 enrolled patients received treatment. The MTD for PF-05212384, administered intravenously once weekly, was estimated to be 154 mg. The most common treatment-related adverse events (AE) were mucosal inflammation/stomatitis (58.4%), nausea (42.9%), hyperglycemia (26%), decreased appetite (24.7%), fatigue (24.7%), and vomiting (24.7%). The majority of patients treated at the MTD experienced only grade 1 treatment-related AEs. Grade 3 treatment-related AEs occurred in 23.8% of patients at the MTD. No treatment-related grade 4–5 AEs were reported at any dose level. Antitumor activity was noted in this heavily pretreated patient population, with two partial responses (PR) and an unconfirmed PR. Eight patients had long-lasting stable disease (&gt;6 months). Pharmacokinetic analyses showed a biphasic concentration–time profile for PF-05212384 (half-life, 30–37 hours after multiple dosing). PF-05212384 inhibited downstream effectors of the PI3K pathway in paired tumor biopsies. Conclusions: These findings demonstrate the manageable safety profile and antitumor activity of the PI3K/mTOR inhibitor PF-05212384, supporting further clinical development for patients with advanced solid malignancies. Clin Cancer Res; 21(8); 1888–95. ©2015 AACR.

The Brain and Body Donation Program (BBDP) at Banner Sun Health Research Institute (http://www.brainandbodydonationprogram.org) started in 1987 with brain‐only donations and currently has banked more than 1600 brains. More than 430 whole‐body donations have been received since this service was commenced in 2005. The collective academic output of the BBDP is now described as the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND). Most BBDP subjects are enrolled as cognitively normal volunteers residing in the retirement communities of metropolitan Phoenix, Arizona. Specific recruitment efforts are also directed at subjects with Alzheimer's disease, Parkinson's disease and cancer. The median age at death is 82. Subjects receive standardized general medical, neurological, neuropsychological and movement disorders assessments during life and more than 90% receive full pathological examinations by medically licensed pathologists after death. The Program has been funded through a combination of internal, federal and state of Arizona grants as well as user fees and pharmaceutical industry collaborations. Subsets of the Program are utilized by the US National Institute on Aging Arizona Alzheimer's Disease Core Center and the US National Institute of Neurological Disorders and Stroke National Brain and Tissue Resource for Parkinson's Disease and Related Disorders. Substantial funding has also been received from the Michael J. Fox Foundation for Parkinson's Research. The Program has made rapid autopsy a priority, with a 3.0‐hour median post‐mortem interval for the entire collection. The median RNA Integrity Number (RIN) for frozen brain and body tissue is 8.9 and 7.4, respectively. More than 2500 tissue requests have been served and currently about 200 are served annually. These requests have been made by more than 400 investigators located in 32 US states and 15 countries. Tissue from the BBDP has contributed to more than 350 publications and more than 200 grant‐funded projects.

Abstract BAFF and a proliferation-inducing ligand (APRIL), which control B cell homeostasis, are therapeutic targets in autoimmune diseases. TACI-Fc (atacicept), a soluble fusion protein containing the extracellular domain of the BAFF–APRIL receptor TACI, was applied in clinical trials. However, disease activity in multiple sclerosis unexpectedly increased, whereas in systemic lupus erythematosus, atacicept was beneficial. In this study, we show that an endogenous soluble TACI (sTACI) exists in vivo. TACI proteolysis involved shedding by a disintegrin and metalloproteinase 10 releasing sTACI from activated B cells. The membrane-bound stub was subsequently cleaved by γ-secretase reducing ligand-independent signaling of the remaining C-terminal fragment. The shed ectodomain assembled ligand independently in a homotypic way. It functioned as a decoy receptor inhibiting BAFF- and APRIL-mediated B cell survival and NF-κB activation. We determined sTACI levels in autoimmune diseases with established hyperactivation of the BAFF–APRIL system. sTACI levels were elevated both in the cerebrospinal fluid of the brain-restricted autoimmune disease multiple sclerosis correlating with intrathecal IgG production, as well as in the serum of the systemic autoimmune disease systemic lupus erythematosus correlating with disease activity. Together, we show that TACI is sequentially processed by a disintegrin and metalloproteinase 10 and γ-secretase. The released sTACI is an immunoregulator that shares decoy functions with atacicept. It reflects systemic and compartmentalized B cell accumulation and activation.