Bivalirudin versus heparin and provisional GP IIb/IIIa inhibitors in patients treated for ST‐segment elevation myocardial infarctions: Comparison of outcomes in a “real‐world” setting

Introduction

The beneficial effects of bivalirudin during primary PCIs are controversially discussed, data on unselected patients are rare. It was the aim of the study to compare bivalirudin versus heparin and provisional glycoprotein IIb/IIIa inhibitors (GPIs) in a “real‐world” study.

Methods

From 05/2013 until 11/2014, the STEMI‐patients in the Bremen STEMI registry were treated with periinterventional bivalirudin; before and after this period the standard anticoagulative treatment was heparin and provisional GPIs.

Results

In 714 patients bivalirudin was used for PCI, this cohort was compared to 683 patients with heparin and provisional GPIs. In patients with bivalirudin a significantly lower rate of hospital bleedings was observed compared to patients with heparin (4.6% vs 8.1%, P < 0.01, multivariate HR 0.57, 95%CI 0.35‐0.93), in an exclusive analysis of severe bleedings a trend toward less bleedings was found in patients with bivalirudin (2.0% vs 3.5%, P = 0.07, multivariate HR 0.66, 95%CI 0.30‐1.42). The rate of stent thromboses reinfarctions and mortality was not different between the bivalirudin and the heparin group. During 1‐year follow‐up bivalirudin was associated with a lower rate of bleedings and no significant differences in stent thromboses, reinfarctions, and mortality. Bivalirudin was not associated with an excess of bleedings or stent thromboses in subgroups that are regularly underrepresented in randomized trials (older patients, women, cardiogenic shock).

Conclusions

In this “real‐world” cohort of patients with STEMI bivalirudin compared to heparin and GPIs was associated with less bleedings and no significant differences in stent thromboses, reinfarctions, and mortality during hospital and long‐term course.

     

Organ preservation treatment using TPF—a pilot study in patients with advanced primary and recurrent cancer of the oral cavity and the maxillary sinus

Purpose

Induction chemotherapy with Taxotere, cisplatin, and 5-fluororacil (TPF) was mainly used in hypopharyngeal and laryngeal cancer patients for larynx preservation. This study aimed to assess feasibility and toxicity in oral cavity and maxillary sinus cancer patients.

Patients and methods

Between 2003 and 2008, 21 patients (18 male, three female; mean age 58 years; 15 patients Eastern Cooperative Oncology Group ≥1) suffering from advanced squamous cell cancers of the oral cavity (seven primaries, eight locoregional recurrences) and the maxillary sinus (six patients) were prospectively treated with three cycles of TPF (q3w) and were scheduled to undergo definitive chemoradiation.

Results

Of 21 patients, 15 (71%) could be treated with all three cycles, one patient with two cycles, and five patients with one cycle. Reasons for incomplete treatment were tumor progression, edema, seizure, bad general condition, sepsis, pneumonia (each once). The infections led to two treatment-related deaths (9.5%). Acute grade III/IV side effects were noted maximally in 11 patients (52%). Main toxicities were afebrile leukopenias and neutropenias and stomatitis. Of 15 patients, six and four patients had a clinical complete or partial remission following three cycles (67%); five patients with recurrences had no response. Ten patients underwent a definitive chemoradiation or radiation (47.6%). After a mean observation time of 17 months, nine patients are alive; one of them developed a local recurrence.

Conclusions

Chemotherapy with TPF is a highly effective treatment with considerable toxicity that needs special expertise which is best assured in a multidisciplinary setting. Pretreated recurrent cancers demonstrated bad response. A target for organ preservation could be the maxillary sinus; due to tumor regression in advanced oral tongue cancer, consecutively, a reduced function has to be encountered.     

Development and implementation of a curricular-wide electronic portfolio system in a school of pharmacy

The Feik School of Pharmacy collaborated with a commercial software development company to create a Web-based e-portfolio system to document student achievement of curricular outcomes and performance in pharmacy practice experiences. The multi-functional system also could be used for experiential site selection and assignment and continuing pharmacy education. The pharmacy school trained students, faculty members, and pharmacist preceptors to use the e-portfolio system. All pharmacy students uploaded the required number of documents and assessments to the program as evidence of achievement of each of the school's curricular outcomes and completion of pharmacy practice experiences.     

Inhibition of phosphodiesterase-4 decreases ethanol intake in mice

Rationale  

Cyclic AMP (cAMP)–protein kinase A signaling has been implicated in the regulation of ethanol consumption. Phosphodiesterase-4 (PDE4) specifically hydrolyzes cAMP and plays a critical role in controlling intracellular cAMP levels in the brain. However, the role of PDE4 in ethanol consumption remains unknown.     

Caffeic acid phenethyl ester inhibits PDGF-induced proliferation of vascular smooth muscle cells via activation of p38 MAPK, HIF-1α, and heme oxygenase-1

Hyperproliferation of vascular smooth muscle cells (VSMCs) is critically involved in the onset of atherosclerosis and restenosis. Although caffeic acid phenethyl ester (CAPE, 1), one of the main constituents of honeybee propolis, has been shown to exert a beneficial effect in models of vascular injury in vivo, detailed mechanistic investigations in vascular cells are scarce. This study has examined the antiproliferative activity of 1 in platelet-derived growth factor (PDGF)-stimulated primary rat aortic VSMCs and aimed to shed light on underlying molecular mechanisms. Compound 1 inhibited the proliferation of VSMCs upon exposure to PDGF in a dose-dependent manner by interfering with cell cycle progression from the G0/1- to the S-phase. Enhanced phosphorylation of p38 mitogen-activated protein kinase (MAPK) as well as stabilization of hypoxia-inducible factor (HIF)-1α and subsequent induction of heme oxygenase-1 (HO-1) could be identified as molecular events contributing to the observed growth arrest in PDGF-activated VSMCs upon exposure to 1.     

Organization and function of the FKBP52 and FKBP51 genes

Best established as components of steroid hormone receptor complexes, it is now clear that the large molecular weight immunophilins, FKBP52 and FKBP51, play important regulatory roles elsewhere in the cell. This review outlines what is known about the organization of the genes, FKBP4 and FKBP5, respectively, encoding these proteins and describes their diverse actions in the nervous system, reproduction, and cancer. The organization of FKBP4 and FKBP5 is very similar among the chordates, and gene expression is influenced by both genetic and epigenetic mechanisms. Recent studies identifying roles of FKBP52 and FKBP51 in the regulation of the microtubule-associated protein tau and microtubule assembly are discussed, as is their interaction with and influence on the transient receptor potential canonical (TRPC) subfamily of ion channel proteins.     

A review of the chemopreventative effects of oral retinoids for internal neoplasms

With the recent data showing that psoriasis patients are at higher risk for systemic malignancies, there is a growing awareness for the need to minimize cancer risks in psoriasis patients. Retinoids as a class of medication have been widely studied as potential agents for cancer chemoprevention. Since they act by inducing cell differentiation and maturation, they may help reverse the pathogenesis of malignancies. Through an extensive literature review, this paper provides an update on the available data on retinoids and their systemic anti-cancer properties. Retinoids appear to be beneficial in the prevention of cutaneous T-cell lymphoma, acute promyelocytic leukemia, head and neck cancers, hepatocellular carcinoma, breast cancer and neuroblastoma. So far the data does not support anti-cancer efficacy of retinoids in the prevention of prostate or pancreatic cancer and may possibly have harmful effects in the pathogenesis of lung cancer in smokers. J Drugs Dermatol. 2011;10(11):1292-1298.     

6-Thioguanine reactivates epigenetically silenced genes in acute lymphoblastic leukemia cells by facilitating proteasome-mediated degradation of DNMT1

Thiopurines including 6-thioguanine ((S)G), 6-mercaptopurine, and azathioprine are effective anticancer agents with remarkable success in clinical practice, especially in effective treatment of acute lymphoblastic leukemia (ALL). (S)G is understood to act as a DNA hypomethylating agent in ALL cells, however, the underlying mechanism leading to global cytosine demethylation remains unclear. Here we report that (S)G treatment results in reactivation of epigenetically silenced genes in T leukemia cells. Bisulfite genomic sequencing revealed that (S)G treatment universally elicited demethylation in the promoters and/or first exons of the genes that were reactivated. (S)G treatment also attenuated the expression of histone lysine-specific demethylase 1 (LSD1), thereby stimulating lysine methylation of the DNA methylase DNMT1 and triggering its degradation via the ubiquitin-proteasomal pathway. Taken together, our findings reveal a previously uncharacterized but vital mechanistic link between (S)G treatment and DNA hypomethylation.