Pediatric mechanical circulatory support

Over the past two decades clinicians and researchers have sought to bring mechanical circulatory support (MCS) to pediatric patients with heart failure. ECMO, IABPs, and VADs have all been used in infants and children as a bridge to myocardial recovery or as a bridge to transplant. However, until recently, a commitment by industry, government, and researchers towards the development of pediatric MCS has not been present, especially in the United States. Advancements in adult VAD design to smaller, quieter, and fully implantable pumps capable of complete outpatient support have sparked curiosity in the application of this technology to children. Also, the increasing success of palliating congenital heart disease is creating an ever-growing cohort of children and adolescents with heart failure. These changing demographics and technological advances have caused a refocus of attention. This is most clearly demonstrated by the international use of several established MCS pediatric and neonatal systems, by the FDAOs increasing proclivity to allow the use of international pediatric VADs in the USA, and by the recent National Heart, Lung, and Blood Institute funding of several institutions to develop pediatric VADs. This review describes the different aspects of pediatric MCS including indications, the features of the various VADs, and their current application in children worldwide.     

Pediatric mechanical circulatory support

Extracorporeal membrane oxygenation (ECMO) is based on technology that has been used clinically for decades. Largely because of its widespread use in pediatric patients with respiratory failure, familiarity with this technology has established ECMO as the most commonly used form of circulatory support for children. However, clinical applications and technical aspects of ECMO support continue to evolve, ensuring the ongoing importance of this modality for pediatric circulatory support. Although traditionally lagging behind development for adult applications, the use of ventricular assist devices (VADs) is expanding in pediatrics. Of particular interest, a number of new VADs designed specifically for children are becoming available, while early development of some innovative devices for pediatric circulatory support is currently underway.     

Pediatric circulatory support: current strategies and future directions. Biventricular and univentricular mechanical assistance

Mechanical circulatory support is gaining increased recognition as a viable treatment option for pediatric patients who suffer from congenital or acquired heart disease. Historically, the treatment options have been very limited for pediatric patients, but recent technological advances, combined with new research into circulatory support devices, are seeking alternative therapeutics options for infants and children. We present a review of the technological advances of mechanical circulatory support in the pediatric population, including the recent emergence of a new class of circulatory support devices for pediatric patients with single ventricle physiology. The National Heart, Lung, and Blood Institute pediatric circulatory support program is discussed, in addition to the use of adult devices in pediatric applications, the Berlin Heart Excor, and several other blood pumps in development for bridge-to-transplant and bridge-to-recovery support. These devices have the potential to generate a paradigm shift in the treatment of the pediatric patients with heart failure--a shift is likely already be underway.     

Medical device evaluation in the United Kingdom: past, present and future

The evaluation of medical devices in the UK has been through many changes since the early hospital equipment assessments in the 1960s. The range of medical devices evaluated has increased and the evaluation reports published have changed, but the evaluation programme continues to be a respected service for the NHS and social care. This review documents the history of the Device Evaluation Service, from its beginnings to the present day, and looks forward to its future. Following an independent strategic review and the Healthcare Industries Task Force (HITF) recommendations, the Device Evaluation Service is now entering a new and exciting developmental phase.     

Medical device evaluation in the United Kingdom: past,present and future

The evaluation of medical devices in the UK has been through many changes since the early hospital equipment assessments in the 1960s. The range of medical devices evaluated has increased and the evaluation reports published have changed, but the evaluation programme continues to be a respected service for the NHS and social care. This review documents the history of the Device Evaluation Service, from its beginnings to the present day, and looks forward to its future. Following an independent strategic review and the Healthcare Industries Task Force (HITF) recommendations, the Device Evaluation Service is now entering a new and exciting developmental phase.     

Poxviruses: past, present and future

The analysis of poxvirus genomes is complex, in part, because of their size (130-360 kb) and the fact that gene content is variable; a common set of 49 genes has been found in all sequenced poxviruses and an additional 41 genes are also present in all sequenced orthopoxviruses. As a group, poxviruses have a very broad range of eukaryotic hosts (including mammals, birds, reptiles and insects) and many poxvirus genes are associated with blocking host anti-viral responses. One consequence of this is that many poxvirus genes are not essential for growth in tissue culture and that extensive passaging in vitro results in the accumulation of mutations, including deletions that result in loss of gene function. Here, we review various comparative analyses of the poxviruses including gene prediction, gene conservation and function, genome organization, and poxvirus taxonomy and evolution.     

Secondary prevention of HIV in the United States: past, current, and future perspectives

To provide a synopsis of past, current, and potential next-generation approaches to prevention for positives (PfP) interventions in the United States. For a variety of reasons, PfP interventions, with the goals of limiting HIV transmission from people living with HIV/AIDS (PLWHA) to others and protecting the health of PLWHA, did not appear with any frequency in the United States until about 2000. Even today, the number and breadth of evidence-based PfP interventions is very limited. Nevertheless, meta-analytic evidence demonstrates that such interventions can be effective, perhaps even more so than interventions targeting HIV-uninfected individuals. We review early and more recent PfP interventions and suggest that next-generation PfP interventions must involve behavioral and biologic components and target any element that affects HIV risk behavior and/or infectivity. Next-generation PfP interventions should include increased HIV testing to identify additional PLWHA, components to initiate and maintain HIV care, to initiate antiretroviral therapy and promote adherence, and to reduce sexual and injection drug use risk behavior, as well as ancillary treatments and referrals to services. Comprehensive next-generation PfP interventions, including all of these elements and effective linkages among them, are discussed.     

Tuberculosis vaccines: the past,present and future

Tuberculosis still remains a leading infectious cause of death worldwide, although the BCG vaccine has been used for 80 years. There is an urgent need to develop improved BCG or new tuberculosis vaccines. This apparently represents a daunting task, since it will take a long time before a vaccine can be declared to be better than the current BCG vaccine, both in experimental and human studies. The current review takes a brief historic look at the use of current BCG vaccine and provides an overview on what are considered to be the key immunologic criteria that have to be met by a new generation of tuberculosis vaccines. It also provides the most up-to-date information on the latest developments in tuberculosis vaccine research, with a focus on mycobacterial organism-based and Mycobacterium tuberculosis antigen-based vaccines. Consideration is also given to the mucosal route of immunization and 'prime and boost' regimens. This review also presents several important tables, highlighting critical components of antituberculosis immunity, the most commonly tested immune adjuvants, the types of novel tuberculosis antigen-based vaccines and the outcome of different heterologous 'prime and boost' vaccination regimens.     

Interpersonal psychotherapy: past, present and future

The authors briefly describe the origins, theory, and development of interpersonal psychotherapy: its roots in clinical outcome research, its spread from major depression to other psychiatric disorders and its increasing dissemination as an empirically validated clinical intervention included in treatment guidelines. They attempt to forecast research, organizational and training issues the growing interpersonal psychotherapy community may face in the future.     

Recombivax-HB: perspectives past, present and future

Hepatitis B disease has caused a heavy burden worldwide. The development of an immunogenic, efficacious and safe vaccine to combat this problem has already eased this burden to some extent. The incorporation of the vaccine into the infant and childhood immunization schedule has led to a decrease in the number of new hepatitis B cases reported each year, and there has been a significant decline in hepatocellular carcinoma in children. This implies that the future will see less hepatitis B disease as the infant and adolescent population that has been immunized ages, meaning that the disease burden should fall even further.     

Artificial skin: past, present and future

The integrity of the skin should be restored as soon as possible whenever the skin gets wounded. Recent research has revealed some of the complex pathways in wound healing. Based on this knowledge, researchers have been looking for better skin substitutes to treat difficultly healing or large wounds. Some of these highly sophisticated wound dressings, also known as bio-dressings, contain material of human or animal origin, e.g. cultured skin cells. Although the ideal skin substitute has not been established yet, the currently available bio-dressings help clinicians close difficultly healing skin wounds.     

The macrophage: past, present and future

As we approach the centenary of Elie Metchnikoff's Nobel Prize (1908), it is opportune to reflect upon the history of macrophage immunobiology, take stock of current knowledge and anticipate questions for the future. Starting from his appreciation of phagocytosis as an important determinant of host defence against infection and injury, we have learned a great deal about the distribution of macrophages throughout the body, their heterogeneous phenotype and complex functions in tissue homeostasis as well as in innate and acquired immunity. Recent discoveries of Toll-like and other plasma membrane, vacuolar and cytosolic recognition molecules have brought the macrophage and closely related dendritic cells to the centre of immunologic attention, but many earlier discoveries of their cellular and molecular properties have laid a broader foundation to the appreciation of their remarkable plasticity and adaptability to local and systemic cues. Discoveries of pro-inflammatory mediators such as TNF and other secretory products have provided valuable insights into the role of macrophages in many acute and chronic disease processes, and led to the development of effective therapeutics. Much remains to be discovered regarding both their specific functions and by study of their general cellular properties, in vitro and in vivo.     

Gleason grading: past, present and future

In 1966 Donald Gleason developed his grading and scoring system for prostatic adenocarcinoma. This classification was refined in 1974 and gained almost universal acceptance, being classified as a category 1 prognostic parameter by the College of American Pathologists. Modifications to the classification were recommended at a conference convened by the International Society of Urological Pathology (ISUP) in 2005. This modified classification has resulted in a significant upgrading of tumours, although some studies have shown a greater concordance between needle biopsy and radical prostatectomy scores when compared to classical Gleason (CG) grading. The ISUP consensus conference recommended that for needle biopsies higher tertiary patterns should be incorporated into the final Gleason score, and this has been correlated with biochemical failure, tumour volume and mortality. Recently the validity of including cribriform glands as a component of Gleason pattern 3 has been questioned and it has been recommended that all tumours showing cribriform architecture should be classified as Gleason pattern 4. The recommendations arising from the 2005 Consensus Conference were largely unsupported by validating data, yet this new grading system has achieved widespread usage. It is unfortunate that recent suggestions for further modification are similarly lacking in supporting evidence. In view of this it is recommended that the Modified Gleason Scoring Classification should continue to be utilized in its original (2005) format and that any future alterations should be implemented only when mandated by tumour-related outcome studies.