Contributors and Solutions to High Out-of-Pocket Costs for Heart Failure Medications.

As expensive therapeutics rise to the fore of heart failure management, out-of-pocket (OOP) medication costs have become increasingly relevant to patient care. Prescription medication costs influence medical decision-making and affect adherence. Yet, individualized cost estimates are seldom available during clinical encounters when prescription decisions are made.

The Economic Burden of Heart Failure with Reduced Ejection Fraction: Living Longer but Poorer?

Treatment of heart failure with reduced ejection fraction (HFrEF) has benefitted from a proliferation of new medications and devices. These treatments carry important clinical benefits, but also come with costs relevant to payers, providers, and patients. Patient out-of-pocket costs have been implicated in the avoidance of medical care, nonadherence to medications, and the exacerbation of health care disparities.

Recurrent leishmaniasis infection isolated in the pleural fluid.

We present a rare case of recurrent leishmaniasis infection in a female in her 80s who re-presented with a pleural effusion. The patient was initially investigated as an outpatient for cytopenia and underwent a bone marrow biopsy which subsequently diagnosed visceral leishmaniasis. Following full treatment, and apparent recovery, she re-presented with pleural effusion, hypoalbuminaemia and cytopenia.

Principal diagnostic features of paediatric foreign body aspiration.

Objectives: The aim of this study is to identify the most common and important features within the presenting history, clinical examination and chest radiograph that are associated with foreign body (FB) aspiration in the paediatric population, to support rationalised decision making in regards to proceeding with diagnostic bronchoscopy.

Methods: A retrospective notes review was conducted of 70 patients over a 12-year period at our tertiary referral centre. Their presenting history, clinical and radiographic signs were documented and univariate logistic regression model used to calculate odds ratios.

The Economic Burden of Heart Failure with Reduced Ejection Fraction: Living Longer but Poorer?

Treatment of heart failure with reduced ejection fraction (HFrEF) has benefitted from a proliferation of new medications and devices. These treatments carry important clinical benefits, but also come with costs relevant to payers, providers, and patients. Patient out-of-pocket costs have been implicated in the avoidance of medical care, nonadherence to medications, and the exacerbation of health care disparities.

Are we cross-matching too much blood for elective open abdominal aortic aneurysm repair?

Objectives: This study aims to identify current blood transfusion requirements in elective open abdominal aortic aneurysm repair and to compare this to an existing maximum surgical blood order schedule.

Methods: We retrospectively identified patients who underwent elective open abdominal aortic aneurysm repair over a 40-month period in our institution. Pre-operative number of units cross-matched and the number of units actually transfused were identified.

In Vitro Generation of Human NK Cells Expressing Chimeric Antigen Receptor Through Differentiation of Gene-Modified Hematopoietic Stem Cells.

NK cells represent a very promising source for adoptive cellular approaches for cancer immunotherapy, and extensive research has been conducted, including clinical trials. Gene modification of NK cells can direct their specificity and enhance their function, but the efficiency of gene transfer techniques is very limited. Here we describe two protocols designed to generate mature human NK cells from gene-modified hematopoietic stem cells.

Cocaine-mediated impact on HIV infection in humanized BLT mice.

Cocaine abuse has been shown to have broad-ranging effects on human immunity. With regards to HIV infection, in vitro studies have shown that cocaine enhances infection of stimulated lymphocytes. Moreover, cohort studies in the pre- and post-HAART era have linked stimulant abuse with increased HIV pathogenesis.

Engineering Cellular Resistance to HIV-1 Infection In Vivo Using a Dual Therapeutic Lentiviral Vector.

We described earlier a dual-combination anti-HIV type 1 (HIV-1) lentiviral vector (LVsh5/C46) that downregulates CCR5 expression of transduced cells via RNAi and inhibits HIV-1 fusion via cell surface expression of cell membrane-anchored C46 antiviral peptide. This combinatorial approach has two points of inhibition for R5-tropic HIV-1 and is also active against X4-tropic HIV-1. Here, we utilize the humanized bone marrow, liver, thymus (BLT) mouse model to characterize the in vivo efficacy of LVsh5/C46 (Cal-1) vector to engineer cellular resistance to HIV-1 pathogenesis.

Engineering HIV-1-resistant T-cells from short-hairpin RNA-expressing hematopoietic stem/progenitor cells in humanized BLT mice.

Down-regulation of the HIV-1 coreceptor CCR5 holds significant potential for long-term protection against HIV-1 in patients. Using the humanized bone marrow/liver/thymus (hu-BLT) mouse model which allows investigation of human hematopoietic stem/progenitor cell (HSPC) transplant and immune system reconstitution as well as HIV-1 infection, we previously demonstrated stable inhibition of CCR5 expression in systemic lymphoid tissues via transplantation of HSPCs genetically modified by lentiviral vector transduction to express short hairpin RNA (shRNA). However, CCR5 down-regulation will not be effective against existing CXCR4-tropic HIV-1 and emergence of resistant viral strains.

Toll-like receptor 2 signaling protects mice from tumor development in a mouse model of colitis-induced cancer.

Inflammatory bowel disease (IBD) is a disorder of chronic inflammation with increased susceptibility to colorectal cancer. The etiology of IBD is unclear but thought to result from a dysregulated adaptive and innate immune response to microbial products in a genetically susceptible host. Toll-like receptor (TLR) signaling induced by intestinal commensal bacteria plays a crucial role in maintaining intestinal homeostasis, innate immunity and the enhancement of intestinal epithelial cell (IEC) integrity.

Identification of a novel human MD-2 splice variant that negatively regulates Lipopolysaccharide-induced TLR4 signaling.

Myeloid differentiation factor 2 (MD-2) is a secreted gp that assembles with TLR4 to form a functional signaling receptor for bacterial LPS. In this study, we have identified a novel alternatively spliced isoform of human MD-2, termed MD-2 short (MD-2s), which lacks the region encoded by exon 2 of the MD-2 gene. Similar to MD-2, MD-2s is glycosylated and secreted.

Involvement of innate and adaptive immunity in a murine model of coronary arteritis mimicking Kawasaki disease.

Kawasaki disease (KD) is the most common cause of acquired cardiac disease and acute vasculitis in children in the developed world. Injection of a cell wall extract isolated from Lactobacillus casei (LCCWE) into mice causes a focal coronary arteritis that histopathologically mimics the coronary lesions observed in KD patients. In this study we used this model to investigate the participation of T cells, B cells, and dendritic cells (DC) in the development of coronary arteritis.

Ubiquitination and de-ubiquitination: role in regulation of signaling by Toll-like receptors.

Signaling by Toll-like receptors (TLRs) has attracted accelerating attention over the past decade because of the central role of TLR signaling in both innate and adaptive immunity. In addition, TLR signaling is now increasingly implicated in a remarkably wide range of diseases that are either caused, or accompanied, by dysregulated inflammation. Much has been learned about the basic signaling framework and participants, as well as how signaling is turned off and fine-tuned.