Citations

Despite knowledge that EGDT improves outcomes in septic patients, staff education on EGDT and compliance with the CPOE order set has been variable. Based on results of a resident survey to identify barriers to decrease severe sepsis/septic shock mortality in the medical intensive care unit (MICU), multifaceted interventions such as educational interventions to improve awareness to the importance of early goal-directed therapy (EGDT), and the use of the Computerized Physician Order Entry (CPOE) order set, were implemented in July 2013. CPOE order set was established to improve compliance with the EGDT resuscitation bundle elements. Orders were reviewed and compared for patients admitted to the MICU with severe sepsis/septic shock in July and August 2013 (controls) and 2014 (following the intervention). Similarly, educational slide sets were used as interventions for residents before the start of their ICU rotations in July and August 2013. While CPOE order set compliance did not significantly improve (78% vs. 76%, p = 0.74), overall EGDT adherence improved from 43% to 68% ( p = 0.0295). Although there was a trend toward improved mortality, this did not reach statistical significance. This study shows that education interventions can be used to increase awareness of severe sepsis/septic shock and improve overall EGDT adherence.

Background Socioeconomic status (SES) is an important predictor for outcomes of chronic diseases. However, it is often unavailable in clinical data. We sought to determine whether an individual housing-based SES index termed HOUSES can influence the likelihood of multiple chronic conditions (MCC) and hospitalisation in a community population. Methods Participants were residents of Olmsted County, Minnesota, aged >18 years, who were enrolled in Mayo Clinic Biobank on 31 December 2010, with follow-up until 31 December 2011. Primary outcome was all-cause hospitalisation over 1 calendar-year. Secondary outcome was MCC determined through a Minnesota Medical Tiering score. A logistic regression model was used to assess the association of HOUSES with the Minnesota tiering score. With adjustment for age, sex and MCC, the association of HOUSES with hospitalisation risk was tested using the Cox proportional hazards model. Results Eligible patients totalled 6402 persons (median age, 57 years; 25th–75th quartiles, 45–68 years). The lowest quartile of HOUSES was associated with a higher Minnesota tiering score after adjustment for age and sex (OR (95% CI) 2.4 (2.0 to 3.1)) when compared with the highest HOUSES quartile. Patients in the lowest HOUSES quartile had higher risk of all-cause hospitalisation (age, sex, MCC-adjusted HR (95% CI) 1.53 (1.18 to 1.98)) compared with those in the highest quartile. Conclusions Low SES, as assessed by HOUSES, was associated with increased risk of hospitalisation and greater MCC health burden. HOUSES may be a clinically useful surrogate for SES to assess risk stratification for patient care and clinical research.

Abstract Purpose: Prostate cancers incite tremendous morbidity upon metastatic growth. We previously identified Asporin (ASPN) as a potential mediator of metastatic progression found within the tumor microenvironment. ASPN contains an aspartic acid (D)-repeat domain and germline polymorphisms in D-repeat-length have been associated with degenerative diseases. Associations of germline ASPN D polymorphisms with risk of prostate cancer progression to metastatic disease have not been assessed. Experimental Design: Germline ASPN D-repeat-length was retrospectively analyzed in 1,600 men who underwent radical prostatectomy for clinically localized prostate cancer and in 548 noncancer controls. Multivariable Cox proportional hazards models were used to test the associations of ASPN variations with risk of subsequent oncologic outcomes, including metastasis. Orthotopic xenografts were used to establish allele- and stroma-specific roles for ASPN D variants in metastatic prostate cancer. Results: Variation at the ASPN D locus was differentially associated with poorer oncologic outcomes. ASPN D14 [HR, 1.72; 95% confidence interval (CI), 1.05–2.81, P = 0.032] and heterozygosity for ASPN D13/14 (HR, 1.86; 95% CI, 1.03–3.35, P = 0.040) were significantly associated with metastatic recurrence, while homozygosity for the ASPN D13 variant was significantly associated with a reduced risk of metastatic recurrence (HR, 0.44; 95% CI, 0.21–0.94, P = 0.035) in multivariable analyses. Orthotopic xenografts established biologic roles for ASPN D14 and ASPN D13 variants in metastatic prostate cancer progression that were consistent with patient-based data. Conclusions: We observed associations between ASPN D variants and oncologic outcomes, including metastasis. Our data suggest that ASPN expressed in the tumor microenvironment is a heritable modulator of metastatic progression. Clin Cancer Res; 22(2); 448–58. ©2015 AACR.

Hidradenocarcinoma is a rare aggressive form of cutaneous adnexal skin carcinoma originating from the sweat gland. Due to its low incidence, prognostic and treatment strategies are still being explored both for primary and advanced disease. This tumor most often presents as either solid or cystic appearing subcutaneous nodules, which may be associated with pruritus or ulceration. To date the mainstay of treatment for local disease has been surgical excision; however, the paucity of historical data available has shown that these tumors often behave aggressively with high rates of local recurrence, metastasis, and poor overall outcomes. There are few case reports describing the utility of radiation therapy in the treatment of hidradenocarcinoma. Herein, we present a case of metastatic apocrine hidradenocarcinoma in a 32-year-old Caucasian male. The patient initially underwent excisional biopsy which confirmed the diagnosis of poorly differentiated, highly infiltrative, apocrine hidradenocarcinoma. He received systemic chemotherapy for metastatic disease, followed by radiation therapy to areas of grossly palpable adenopathy. Prior to radiation therapy the patient had an enlarged hypermetabolic conglomerate of lymph nodes in the right axilla, and borderline enlarged low activity nodes within the left axilla. He received 3 cycles of chemotherapy followed by tamoxifen and radiation therapy (50.4 Gy in 28 fractions) to areas of progressive disease in the bilateral axilla, lower neck, and axillary skin. Following treatment, the patient had complete resolution of skin nodules and improvement of his pruritus. While the role of radiation therapy in the treatment of hidradenocarcinoma has not been well established, this case report demonstrated the potential benefit of external beam radiotherapy in the management of this rare disease.

Human T-cell lymphoma virus (HTLV)-associated adult T-cell leukemia lymphoma is a rare cancer in the United States, but there are several areas around the world where the virus is endemic. HTLV-associated adult T-cell leukemia lymphoma has been associated with leukemic arthropathy. We present a patient with HTLV-associated adult T-cell leukemia lymphoma with leukemic arthropathy. Although non-steroidal anti-inflammatory drugs and chemotherapy are often used for treatment, we describe the successful use of radiation therapy in the palliative relief of symptoms from leukemic arthropathy.

ABSTRACT Although the role of ERα in regulating bone metabolism has been extensively studied, ERβ has been largely dismissed as a relevant modulator of bone mass. Previous studies examining ERβ utilized a germline knockout mouse expressing transcript variants of ERβ and displaying systemic hormonal changes that confounded interpretation of the skeletal phenotype. Thus, we used a conditional ERβ mouse model to achieve deletion of ERβ specifically in early osteoprogenitor cells using the Prx1-Cre driver. We observed marked increases in the trabecular bone volume fraction (of 58% [p < 0.003] and 93% [p < 0.0003] in 6- and 12-week-old female ERβPrx1–CKO mice, respectively) but no changes in cortical bone. Serum estradiol and IGF-I levels were unaltered in ERβPrx1–CKO mice. Bone formation and resorption indices by histomorphometry and serum assays were unchanged in these mice, suggesting that alterations in bone turnover may have occurred early in development. However, the ratio of colony-forming unit-osteoblasts (CFU-OBs) to CFU-fibroblasts (CFU-Fs) was increased in bone marrow cultures from ERβPrx1–CKO compared with control mice, indicating increased differentiation of osteoblast precursor cells into osteoblasts in ERβPrx1–CKO mice. Detailed quantitative polymerase chain reaction analyses of 128 genes in 16 prespecified pathways revealed significant downregulation of 11 pathways in ERβPrx1–CKO mice. Thus, deletion of ERβ specifically in osteoblast lineage cells, in the absence of all splice variants, increases trabecular bone mass and modulates multiple pathways related to bone metabolism. These findings suggest that pharmacological inhibition of ERβ in bone may provide a novel approach to treat osteoporosis. © 2015 American Society for Bone and Mineral Research.