Patient age is related to decision-making, treatment selection, and perceived quality of life in breast cancer survivors

BACKGROUND: Patients with breast cancer must choose among a variety of treatment options when first diagnosed. Patient age, independent of extent of disease, is also related to quality of life. This study examined the impact of patient age on treatment selected, factors influencing this selection, and perceived quality of life. METHODS: A 62-question survey evaluating breast cancer treatment and quality of life was mailed to breast cancer survivors. Responses were stratified by age (<50, 50-65, >65 years) and extent of disease. RESULTS: Of the 1,131 surveys mailed, 402 were included for analysis. There were 104, 179, and 119 women aged <50, 50-65, and >65 years, respectively. The median patient age was 58 years, and the average interval from diagnosis to survey participation was 31.5 months. CONCLUSIONS: Young women were more likely to have undergone aggressive therapies and had better physical functioning than old women. Old patients reported good quality of life and body image. Clinicians should consider patient age when discussing breast cancer treatment options

Improving Antimicrobial Stewardship Programs in Small Community Hospitals Through an Assessment and Feedback Model

Small community hospitals often lack expertise and resources for antimicrobial stewardship program implementation. Using an assessment-and-feedback model, Nebraska ASAP performed onsite assessment of antimicrobial stewardship efforts in 5 small community hospitals and provided facility specific feedback on implementation/augmentation of antimicrobial stewardship program. As a result of this model, participating small community hospitals were able to increase the number of antimicrobial stewardship core elements implemented while reducing antibiotic use and incidence of CDI.https://digitalcommons.unmc.edu/asap_pres/1001/thumbnail.jp

A pathologically expanded, clonal lineage of IL-21-producing CD4+ T cells drives inflammatory neuropathy.

Inflammatory neuropathies, which include chronic inflammatory demyelinating polyneuropathy (CIDP) and Guillain Barré syndrome (GBS), result from autoimmune destruction of the PNS and are characterized by progressive weakness and sensory loss. CD4+ T cells play a key role in the autoimmune destruction of the PNS. Yet, key properties of pathogenic CD4+ T cells remain incompletely understood. Here, we used paired single-cell RNA-Seq (scRNA-Seq) and single-cell T cell receptor-sequencing (scTCR-Seq) of peripheral nerves from an inflammatory neuropathy mouse model to identify IL-21-expressing CD4+ T cells that were clonally expanded and multifunctional. These IL-21-expressing CD4+ T cells consisted of 2 transcriptionally distinct expanded cell populations, which expressed genes associated with T follicular helper (Tfh) and T peripheral helper (Tph) cell subsets. Remarkably, TCR clonotypes were shared between these 2 IL-21-expressing cell populations, suggesting a common lineage differentiation pathway. Finally, we demonstrated that IL-21 receptor-KO (IL-21R-KO) mice were protected from neuropathy development and had decreased immune infiltration into peripheral nerves. IL-21 signaling upregulated CXCR6, a chemokine receptor that promotes CD4+ T cell localization in peripheral nerves. Together, these findings point to IL-21 signaling, Tfh/Tph differentiation, and CXCR6-mediated cellular localization as potential therapeutic targets in inflammatory neuropathies

Frequently Identified Gaps in Antibiotic Stewardship Programs in Critical Access Hospitals

Background: Nebraska (NE) Infection Control Assessment and Promotion Program (ICAP) is a CDC funded project. ICAP team works in collaboration with NE Department of Health and Human Services (NEDHHS) to assess and improve infection prevention and control programs (IPCP) in various health care settings including resource limited settings like critical access hospitals (CAH). Little is known about the existing gaps in antimicrobial stewardship programs (ASP) of CAH. Hence, we decided to study the current level of ASP activities and factors associated with these activities in CAH. Methods: NE ICAP conducted on-site surveys in 36 CAH from October 2015 to February 2017. ASP activities related to the 7 CDC recommended core elements (CE) including leadership support (LS), accountability, drug expertise (DE), action, tracking, reporting, and education were assessed using a CDC Infection Control Assessment Tool for acute care hospitals. Descriptive analyses evaluated CAH characteristics and frequency of CE implementation. Fisher’s exact, Mann–Whitney, and Kruskal–Wallis tests were used for statistical analyses examining the association of various factors with level of ASP activities. Results: The 36 surveyed CAH had a median of 20 (range 10–25) beds and employed a median of 0.4 (range 0.1–1.6) infection preventionist (IP) full-time equivalent (FTE)/25-bed. Frequency of CE implementation varied among CAH with action and LS as the most (69%) and least (28%) frequently implemented elements, respectively. Close to half (47%) of surveyed CAH had implemented ≥4 CE but only 14% of facilities had all 7 CE. Median bed size and IP FTE/25-bed were similar among CAH with 0–2, 3-5, or ≥6 CE in place. CAH with LS or accountability for ASP implemented higher median numbers of the remaining CE compared with CAH without LS or accountability (5 vs. 2, P \u3c 0.01 and 4 vs. 2, P \u3c 0.01, respectively). Facilities with The presence of LS, accountability and drug expertise were more likely to have all 4 remaining CE implemented than others (56% vs. 8%, P \u3c 0.01). Conclusion: LS, accountability, and DE are important factors for the implementation of the remaining 4 CE in CAH. Although LS was the least frequently implemented CE, when present was associated with implementation of most of the other CE. Acquiring LS will facilitate implementation of additional ASP efforts in CAH.https://digitalcommons.unmc.edu/asap_pres/1000/thumbnail.jp

Clinical and serological features of systemic sclerosis in a multicenter African American cohort: Analysis of the genome research in African American scleroderma patients clinical database.

Racial differences exist in the severity of systemic sclerosis (SSc). To enhance our knowledge about SSc in African Americans, we established a comprehensive clinical database from the largest multicenter cohort of African American SSc patients assembled to date (the Genome Research in African American Scleroderma Patients (GRASP) cohort).African American SSc patients were enrolled retrospectively and prospectively over a 30-year period (1987-2016), from 18 academic centers throughout the United States. The cross-sectional prevalence of sociodemographic, clinical, and serological features was evaluated. Factors associated with clinically significant manifestations of SSc were assessed using multivariate logistic regression analyses.The study population included a total of 1009 African American SSc patients, comprised of 84% women. In total, 945 (94%) patients met the 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for SSc, with the remaining 64 (6%) meeting the 1980 ACR or CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) criteria. While 43% were actively employed, 33% required disability support. The majority (57%) had the more severe diffuse subtype and a young age at symptom onset (39.1 ± 13.7 years), in marked contrast to that reported in cohorts of predominantly European ancestry. Also, 1 in 10 patients had a severe Medsger cardiac score of 4. Pulmonary fibrosis evident on computed tomography (CT) chest was present in 43% of patients and was significantly associated with anti-topoisomerase I positivity. 38% of patients with CT evidence of pulmonary fibrosis had a severe restrictive ventilator defect, forced vital capacity (FVC) ≤50% predicted. A significant association was noted between longer disease duration and higher odds of pulmonary hypertension, telangiectasia, and calcinosis. The prevalence of potentially fatal scleroderma renal crisis was 7%, 3.5 times higher than the 2% prevalence reported in the European League Against Rheumatism Scleroderma Trials and Research (EUSTAR) cohort.Our study emphasizes the unique and severe disease burden of SSc in African Americans compared to those of European ancestry

Kinetic Assessment and Therapeutic Modulation of Metabolic and Inflammatory Profiles in Mice on a High-Fat and Cholesterol Diet

The kinetics of metabolic and inflammatory parameters associated with obesity were evaluated in a murine diet-induced obesity (DIO) model using a diet high in fat and cholesterol. Cellular infiltration and mediator production were assessed and shown to be therapeutically modulated by the PPARgamma agonist rosiglitazone. C57BL/6 mice were maintained on a 45% fat/ 0.12% cholesterol (HF/CH) or Chow diet for 3, 6, 16, or 27 weeks. Flow cytometry was employed to monitor peripheral blood monocytes and adipose tissue macrophages (ATM). Gene expression and protein analysis methods were used to evaluate mediator production from total epididymal fat (EF), stromal vascular fraction (SVF), and sorted SVF cells. To investigate therapeutic intervention, mice were fed a HF/CH diet for 12 weeks and then a diet formulated with rosiglitazone (5 mg/kg) for an additional 6 weeks. A HF/CH diet correlated with obesity and a dramatic proinflammatory state. Therapeutic intervention with rosiglitazone attenuated the HF/CH induced inflammation. In addition, a novel population was found that expressed the highest levels of the pro-inflammatory mediators CCL2 and IL-6

Diet diversity in pastoral and agro-pastoral households in Ugandan rangeland ecosystems

We explore how diet diversity differs with agricultural seasons and between households within pastoral and agro-pastoral livelihood systems, using variety of foods consumed as a less complex proxy indicator of food insecurity than benchmark indicators like anthropometry and serum nutrients. The study was in the central part of the rangelands in Uganda. Seventy nine households were monitored for three seasons, and eight food groups consumed during a 24 hour diet recall period used to create a household diet diversity score (HDDS). Mean HDDS was 3.2, varied significantly with gender, age, livelihood system and season (p < .001, F = 15.04), but not with household size or household head’s education level. Agro-pastoralists exhibited lower mean diet diversity than pastoralists (p < .01, F = 7.84) and among agro-pastoralists, households headed by persons over 65 years were most vulnerable (mean HDDS 2.1). This exploratory study raises issues requiring further investigation to inform policies on nutrition security in the two communities

Efficacy and Safety of Lenabasum, a Cannabinoid Type 2 Receptor Agonist, in a Phase 3 Randomized Trial in Diffuse Cutaneous Systemic Sclerosis

INTRODUCTION: Efficacy and safety of lenabasum, a cannabinoid type 2-receptor agonist, was tested in a Phase 3 study in patients with diffuse cutaneous systemic sclerosis (dcSSc). METHODS: A multi-national double-blind study was conducted in 365 dcSSc patients who were randomized and dosed 1:1:1 with lenabasum 20 mg, lenabasum 5 mg, or placebo, each twice daily and added to background treatments including immunosuppressive therapies (IST). RESULTS: The primary endpoint, ACR Combined Response Index in dcSSc (ACR-CRISS) score at Week 52, lenabasum 20 mg BID versus placebo, was not met, with ACR-CRISS scores of 0.888 versus 0.887, P = 0.4972, mixed models repeated measures (MMRM). Change in modified Rodnan Skin Score (mRSS) at Week 52 was -6.7 versus -8.1 points for lenabasum 20 mg BID versus placebo, P = 0.1183, MMRM. Pre-specified analyses showed higher ACR-CRISS scores, greater improvement in mRSS, and less decline in forced vital capacity in subjects on background mycophenolate and those receiving IST for ≤ 1 year duration. No deaths or excess in serious or severe adverse events related to lenabasum were observed. CONCLUSIONS: A benefit of lenabasum in dcSSc was not demonstrated. The majority of patients were treated with background IST, and treatment with MMF in particular was associated with better outcomes. This supports the use of IST in the treatment of dcSSc, and highlights the challenge of demonstrating a treatment effect when investigational treatment is added to standard of care IST. These findings have relevance to trial design in SSc, as well as clinical care

Induction of interleukin-8 preserves the angiogenic response in HIF-1 alpha-deficient colon cancer cells

authorHypoxia inducible factor-1 (HIF-1) is considered a crucial mediator of the cellular response to hypoxia through its regulation of genes that control angiogenesis^1, ^2, ^3, ^4. It represents an attractive therapeutic target^5, ^6 in colon cancer, one of the few tumor types that shows a clinical response to antiangiogenic therapy^7. But it is unclear whether inhibition of HIF-1 alone is sufficient to block tumor angiogenesis^8, ^9. In HIF-1_α knockdown DLD-1 colon cancer cells (DLD-1^HIF-kd), the hypoxic induction of vascular endothelial growth factor (VEGF) was only partially blocked. Xenografts remained highly vascularized with microvessel densities identical to DLD-1 tumors that had wild-type HIF-1_α (DLD-1^HIF-wt). In addition to the preserved expression of VEGF, the proangiogenic cytokine interleukin (IL)-8 was induced by hypoxia in DLD-1^HIF-kd but not DLD-1^HIF-wt cells. This induction was mediated by the production of hydrogen peroxide and subsequent activation of NF-_KB. Furthermore, the KRAS oncogene, which is commonly mutated in colon cancer, enhanced the hypoxic induction of IL-8. A neutralizing antibody to IL-8 substantially inhibited angiogenesis and tumor growth in DLD-1^HIF-kd but not DLD-1^HIF-wt xenografts, verifying the functional significance of this IL-8 response. Thus, compensatory pathways can be activated to preserve the tumor angiogenic response, and strategies that inhibit HIF-1α may be most effective when IL-8 is simultaneously targeted