Statin therapy across the lifespan: evidence in major age groups.

This review provides needed perspective on statin efficacy and safety in individuals under 40, 40-75, and > 75 years of age. Starting with the 2013 ACC-AHA cholesterol guidelines extensive evidence base on randomized controlled trials (RCTs) we added references in the past 5 years that discussed statin efficacy and safety over the life span. In those under 40, statins are primarily used for treatment of severe hypercholesterolemia, often familial, and they are well tolerated. In middle-aged adults, statins have strong evidence for benefit in primary and secondary prevention trials; however, in primary prevention, a clinician-patient risk discussion should precede statin prescription in order to determine appropriate treatment. In those over 75, issues of statin intensity and net benefit loom large as associated comorbidity, polypharmacy, and potential for adverse effects impact the decision to use statins with RCT data strongest in support of use in secondary prevention. Statin drugs have been studied by RCTs in a large number of individuals. In those groups shown to benefit, statins have reduced the risk of atherosclerotic cardiovascular disease with few side effects as compared to controls. This review has detailed considerations that should occur when statins are given to individuals in different age groups.

Etiology of orbital fractures at a level I trauma center in a large metropolitan city.

BACKGROUND/PURPOSE: Orbital fractures are a common facial fracture managed by multiple surgical specialties. Methods: A retrospective review of the electronic medical records of patients (age, 18-85 years) presenting to Northwestern Memorial Hospital and Northwestern Medical Faculty Foundation in Chicago, IL, USA with International Classification of Diseases, Ninth Revision codes for facial fractures or CPT (Current Procedural Terminology) codes for orbital fracture repair. RESULTS: A review of the electronic medical records identified 504 individual incidents of orbital fractures with available imaging for review. The most common location for an orbital fracture was a floor fracture (48.0%) followed by a medial wall fracture (25.2%). Left-sided orbital fractures were statistically significantly more common than right-sided orbital fractures (99% confidence interval). Orbital fractures were more prevalent in younger age groups. The mean patient age was 39.3 years. The most common cause of all orbital fractures was assault followed by falls. However, falls were the most common cause of orbital fractures in women and in patients aged 50 years and older. Evaluation by an ophthalmologist occurred in 62.8% of orbital fracture patients, and evaluation by a team comprising the facial trauma service (Otolaryngology, Plastic Surgery, and Oral and Maxillofacial Surgery) occurred in 81.9% of orbital fracture patients. CONCLUSION: Assault was the largest cause of all orbital fractures, and occurred most commonly in young males. Assaulted patients were more likely to have left-sided fractures compared to nonassaulted patients. In patients aged 50 years and older, falls were the most common cause of orbital fractures.

Anti-angiogenic SPARC peptides inhibit progression of neuroblastoma tumors.

BACKGROUND: New, more effective strategies are needed to treat highly aggressive neuroblastoma. Our laboratory has previously shown that full-length Secreted Protein Acidic and Rich in Cysteine (SPARC) and a SPARC peptide corresponding to the follistatin domain of the protein (FS-E) potently block angiogenesis and inhibit the growth of neuroblastoma tumors in preclinical models. Peptide FS-E is structurally complex and difficult to produce, limiting its potential as a therapeutic in the clinic. RESULTS: In this study, we synthesized two smaller and structurally more simple SPARC peptides, FSEN and FSEC, that respectively correspond to the N-and C-terminal loops of peptide FS-E. We show that both peptides FSEN and FSEC have anti-angiogenic activity in vitro and in vivo, although FSEC is more potent. Peptide FSEC also significantly inhibited the growth of neuroblastoma xenografts. Histologic examination demonstrated characteristic features of tumor angiogenesis with structurally abnormal, tortuous blood vessels in control neuroblastoma xenografts. In contrast, the blood vessels observed in tumors, treated with SPARC peptides, were thin walled and structurally more normal. Using a novel method to quantitatively assess blood vessel abnormality we demonstrated that both SPARC peptides induced changes in blood vessel architecture that are consistent with blood vessel normalization. CONCLUSION: Our results demonstrate that SPARC peptide FSEC has potent anti-angiogenic and anti-tumorigenic effects in neuroblastoma. Its simple structure and ease of production indicate that it may have clinical utility in the treatment of high-risk neuroblastoma and other types of pediatric and adult cancers, which depend on angiogenesis.

Relationship of EGFR mutations, expression, amplification, and polymorphisms to epidermal growth factor receptor inhibitors in the NCI60 cell lines.

PURPOSE: The mechanism of sensitivity and resistance to epidermal growth factor receptor (EGFR) inhibitors is incompletely understood, particularly in cancers other than non-small-cell lung cancer (NSCLC). To understand the variable response to this class of drugs, we used the NCI60 cancer cell lines. We aimed to determine if there are interactions between EGFR expression, mutations, polymorphisms, and gene amplification, and whether these factors are associated with variability in response to EGFR inhibitors. EXPERIMENTAL DESIGN: The EGFRVIII and tyrosine kinase (TK) domain mutations were examined in the NCI60 cancer cell lines. Five polymorphisms, -216G/T, -191C/A, intron 1 (CA)n, R497K, and 2607A/G, were genotyped. EGFR amplification was also assessed with high-density single-nucleotide polymorphism chip and real-time PCR, respectively. The results were correlated with cytotoxicity data for erlotinib and other 11 EGFR inhibitors, as well as other publicly available data for these lines. RESULTS: All 12 inhibitors behaved similarly. No EGFRVIII but putative TK mutations in two cell lines were found. Both mutant cell lines were insensitive to all inhibitors. Meanwhile, response did not correlate with EGFR amplification but with EGFR gene expression, especially in the cell lines with relatively normal gene status. In addition, EGFR expression was associated with the -216G/T polymorphism but not with the intron 1 (CA)n polymorphism. A combination of -216G/T and R497K polymorphisms was weakly associated with drug response. CONCLUSIONS: These observations suggest that in addition to TK mutations, germ-line variability may also contribute to the pharmacodynamics of EGFR inhibitors, particularly when EGFR is genetically normal.