Mechanical,inflammatory, and embolic complications of myocardial infarction: An emergency medicine review

IntroductionDespite the declining incidence of coronary heart disease (CHD) in the United States, acute myocardial infarction (AMI) remains an important clinical entity, with many patients requiring emergency department (ED) management for mechanical, inflammatory, and embolic complications.ObjectiveThis narrative review provides an evidence-based summary of the current data for the emergency medicine evaluation and management of post myocardial infarction mechanical, inflammatory, and embolic complications.DiscussionWhile 30-day mortality rate after AMI has decreased in the past two decades, it remains significantly elevated at 7.8%, owing to a wide variety of subacute complications evolving over weeks. Mechanical complications such as ventricular free wall rupture, ventricular septal rupture, mitral valve regurgitation, and formation of left ventricular aneurysms carry significant morbidity. Additional complications include ischemic stroke, heart failure, renal failure, and cardiac dysrhythmias. This review provides several guiding principles for management of these complications. Understanding these complications and an approach to the management of various complications is essential to optimizing patient care.ConclusionsMechanical, inflammatory, and embolic complications of AMI can result in significant morbidity and mortality. Physicians must rapidly diagnose these conditions while evaluating for other diseases. In addition to understanding the natural progression of disease and performing a focused physical examination, an electrocardiogram and bedside echocardiogram provide quick, noninvasive determinations of the underlying pathophysiology. Management varies by presentation and etiology, but close consultation with cardiology and cardiac surgery is recommended.     

Mechanical ventilation considerations in complex congenital heart disease.

It is the philosophy of our institution to provide primary surgical repair of complex congenital heart defects to avoid pulmonary and myocardial damage that occurs over time. Application of knowledge of the normal physiology and a clear understanding of the physiologic alterations of complex lesions are essential in understanding the effect of positive-pressure ventilation in complex CHD. The care and management of patients with CHD have a great deal to do with ventilatory management, which can be life-threatening when not fully understood but lifesaving when mastered. A dedicated team approach enhances communication and collaborative practice, which provides optimal patient management and outcome.     

Pharmacokinetics in children: history, considerations, and applications

Crucial to safe pharmacological intervention in the pediatric population is a thorough understanding of the pharmacokinetic and pharmacodynamic differences in children as opposed to adults. This article discusses these differences and clarifies factors related to medication prescribing and administration techniques.     

Predictive genetic testing for drug-induced liver injury: considerations of clinical utility

Genetic predisposition to drug-induced liver injury may be due to variation in both pharmacokinetic and pharmacodynamic pathways. Recent genome-wide association studies have identified, in the human leukocyte antigen (HLA) alleles, strong genetic factors that predispose to liver injury on exposure to any of several drugs. Although the genetic associations have provided mechanistic insights, none has been developed as a predictive test. Further work in this area, in combination with other "-omics" technologies, is needed to develop tests that are both clinically useful and cost-effective.     

Helicobacter pylori strain-specific differences in genetic content, identified by microarray, influence host inflammatory responses

Helicobacter pylori enhances the risk for ulcer disease and gastric cancer, yet only a minority of H. pylori-colonized individuals develop disease. We examined the ability of two H. pylori isolates to induce differential host responses in vivo or in vitro, and then used an H. pylori whole genome microarray to identify bacterial determinants related to pathogenesis. Gastric ulcer strain B128 induced more severe gastritis, proliferation, and apoptosis in gerbil mucosa than did duodenal ulcer strain G1.1, and gastric ulceration and atrophy occurred only in B128+ gerbils. In vitro, gerbil-passaged B128 derivatives significantly increased IL-8 secretion and apoptosis compared with G1.1 strains. DNA hybridization to the microarray identified several strain-specific differences in gene composition including a large deletion of the cag pathogenicity island in strain G1.1. Partial and complete disruption of the cag island in strain B128 attenuated induction of IL-8 in vitro and significantly decreased gastric inflammation in vivo. These results indicate that the ability of H. pylori to regulate epithelial cell responses related to inflammation depends on the presence of an intact cag pathogenicity island. Use of an H pylori whole genome microarray is an effective method to identify differences in gene content between H. pylori strains that induce distinct pathological outcomes in a rodent model of H. pylori infection.     

Genetic testing: practical, ethical, and counseling considerations

Genetic testing is becoming a much more common practice in medicine today. This presents a unique set of challenges for medical professionals in virtually all specialties. The practical aspects of determining which test to order, and in interpreting the result accurately in the context of the family history, can be difficult. Additionally, the ethical conundrums that frequently present themselves when genetic risk assessment and/or genetic testing is being considered can be daunting. These challenges present real concerns for medical professionals and patients alike. Included in this article is a review of some of the practical and ethical complexities associated with genetic testing. Pretest and posttest genetic counseling is also emphasized as an important and essential process in today's medical practice.     

Pharmacovigilance and biosimilars: considerations,needs and challenges

Introduction: Biosimilars are biologic medicines that are highly similar to approved biologics, notwithstanding minor differences in clinically inactive components. Since 2007, biosimilars have been approved for use in patients in the European Union (EU) and other regions. European experience provides several lessons as the United States (US) healthcare system prepares for biosimilar approvals. These lessons emphasize the need for adequate efficacy and safety studies, post-marketing surveys and a robust pharmacovigilance system that can accurately track and trace biologics, including biosimilars and their reference products, from the patient to the manufacturer.

Areas covered: We review the EU experience with biosimilar pharmacovigilance and discuss the implications for biosimilar pharmacovigilance in the USA. Furthermore, we review several aspects of biosimilar pharmacovigilance, including cohort event monitoring, traceability, biosimilar interchangeability, pharmacovigilance system development, nomenclature and counterfeit tracking.

Expert opinion: The availability of biosimilars as lower-cost biologics must carefully consider issues of safety, efficacy and traceability. Stringent pharmacovigilance procedures are required to detect potential differences in safety signals between biosimilars and their reference products. Pharmacovigilance of biologics should include processes that are easily used by prescribing practitioners to ensure that data are consistent and new safety signals are properly reported and assigned to the correct product.     

Large molecular size EDTA-resistant complexes containing S100A12, ERAC, in serum during inflammatory conditions

The pro-inflammatory, leukocyte-derived S100A12 protein occurs as calcium-dependent oligomers in serum, while EDTA plasma from the majority of healthy individuals contains only monomers. Addition of 5 mM EDTA to serum leads to a rapid dissociation of the oligomers in most samples. However, using gel permeation chromatography, we have found that sera from some patients and seemingly healthy individuals contain molecular complexes in the 400-1000 kDa range reacting with anti-S100A12 even in the presence of EDTA; for these we introduce the name ERAC (EDTA Resistant S100A12 Complexes). Based upon monoclonal antibodies and the lateral flow principle, we have developed a quantitative rapid ERAC test giving results within 10 minutes. The highest prevalence of ERAC positivity was found in sera from patients with concomitant rheumatoid arthritis and coronary heart disease. The structure of ERAC is not yet known. Further studies are needed to analyse the mechanism behind the appearance of ERAC and the possible association with inflammatory-related diseases.     

Innovation in nursing management: professional, management and methodological considerations

There are many changes occurring in the National Health Service (NHS) at this time, not just to economic and funding policies, but also at the very heart of nursing care delivery. The introduction of 'managerialism' into the senior clinical grades of nursing, midwifery and other professional staff has characterized the past few years. Against this backdrop is the increasing belief that NHS organizations must find improved ways of delivering patient care and other services. This has inexorably led to the consideration of diffusing innovation into practice as a way to improve performance and competitiveness. While there have been a number of clinical attempts at understanding this process, there has been very little written about innovation from the perspective of the nurse (or midwifery) clinical manager. This paper discusses some of the issues surrounding management innovation including the planning of interventions aimed at introducing innovation, and some of the methodological difficulties of studying complex organizations. The wider issues of innovation, nursing management and professional staff are also discussed.     

Heart transplantation in children: indications, complications, and management considerations.

Heart transplantation in children has increased in the last 5 years because of the availability of cyclosporine and improved surgical techniques. The primary indications for transplantation in children are dilated cardiomyopathy and complex congenital heart disease. The major complications affecting morbidity and mortality are infection and rejection. However, the development of accelerated coronary artery disease represents a serious complication limiting long-term survival. Successful rehabilitation and long-term survival depend on careful selection of potential recipients, application of stringent medical and psychosocial criteria, operative technique, comprehensive medical surveillance, and thorough and effective patient and family education.