Is there a role for melatonin in the ICU?

Summary In the last decade, there have been significant developments in the understanding of the hormone melatonin in terms of its physiology, regulatory role and potential utility in various domains of clinical medicine. Melatonin’s purported properties include, among others, regulation of mitochondrial function, anti-inflammatory, anti-oxidative and neuro-protective effects, sleep promotion and immune enhancement. As such, its role has been explored specifically in the critical care setting in terms of many of these properties. This review addresses the physiological basis for considering melatonin in the critical care setting as well as the current evidence pertaining to its potential utility Contributions of the study This review examines and discusses the role of melatonin in the intensive care unit in terms of sleep, delirium and sepsis, both the physiology and as a therapy.     

Is there a role for subcutaneous furosemide in the community and hospice management of end-stage heart failure?

Patients with advanced chronic heart failure (CHF) can experience 'revolving door' admissions, often for parenteral diuretics, when time at home is precious. Home intravenous diuretic services are patchy. This retrospective review describes 43 consecutive episodes of continuous subcutaneous infusion of furosemide (CSCI-F) in 32 advanced CHF patients; 28 episodes aiming to correct fluid balance and prevent hospital admission and 15 aiming to prevent symptoms in the dying. Overall, 26/28 (93%) avoided hospital admission. Weight loss occurred in 20/28 (70%): a median loss of 5.6?kg [interquartile range (IQR) 0.1-8.9]). The daily dose of furosemide ranged from 40 to 250?mg. The median number of days on CSCI-F was 10.5 (range 2-48; IQR 6-13.8). Site reactions occurred in 10/43 (23%); all of which were mild except two, one of which required oral antibiotics. Symptoms were controlled in all 15 dying patients. CSCI-F for patients with advanced CHF is effective in terms of weight loss and prevention of hospital admission with the heart failure nurse specialist playing a key overall management role in selection and monitoring. As the majority of community and hospice nurses have access to and are familiar with CSCI pumps, this practice should be nationally transferable. The role in the dying patient requires further assessment.     

Angiopoietin/tie‐2 as mediators of angiogenesis: a role in congestive heart failure?

Angiogenic factors, in particular vascular endothelial growth factor (VEGF) and the angiopoietins, Ang-1 and -2, have recently generated significant interest, especially in oncology. The process of angiogenesis is also thought to occur in response to ischaemic conditions, which lie at the core of cardiovascular disease states such as coronary artery disease and congestive heart failure. However, current data do not conclusively show evidence of angiogenesis per se in these conditions, despite (for example) the presence of high levels of VEGF and Ang-2. High levels of these angiogenic factors in heart disease also have not translated into clinically significant new vessel formation, as in accelerated cancer growth or proliferative retinopathy. Indeed, we would hypothesize that these angiogenic markers--especially the angiopoietins--do not necessarily translate into new vessel formation in congestive heart failure (CHF), but may well reflect disturbances of endothelial integrity in CHF.     

Inhibition of 11beta-HSD1 as a novel treatment for the metabolic syndrome: do glucocorticoids play a role?

The metabolic syndrome (syndrome X) is a cluster of risk factors and a common cause of cardiovascular disease in humans. Although the underlying mechanism for metabolic syndrome is still poorly understood, recent clinical data and studies with transgenic animals implicate elevated intracellular glucocorticoid tone in the etiology of metabolic syndrome. Development of selective inhibitors of 11beta-hydroxysteroid dehydrogenase (11beta-HSD)-1 and their use in rodent animal disease models encompassing several aspects of metabolic syndrome indicate the possibility of therapeutic intervention. This review will focus on recent advances in our understanding of the role of 11beta-HSD1 in metabolic disorders and other disease processes.     

Thymosin β4: multiple functions in protection,repair and regeneration of the mammalian heart

Introduction: Despite recent improvements in interventional medicine, cardiovascular disease still represents the major cause of morbidity worldwide, with myocardial infarction being the most common cardiac injury. This has sustained the development of several regenerative strategies based on the use of stem cells and tissue engineering approaches in order to achieve cardiac repair and regeneration by enhancing coronary neovascularization, modulating acute inflammation and supporting myocardial regeneration to provide new functional muscle.

Areas covered: The actin monomer binding peptide, Thymosin β4 (Tβ4), has recently been described as a powerful regenerative agent with angiogenic, anti-inflammatory and cardioprotective effects on the heart and which specifically acts on its resident cardiac progenitor cells. In this review we will discuss the state of the art regarding the many roles of Tβ4 in preserving and regenerating the mammalian heart, with specific attention to its ability to activate the quiescent adult epicardium and specific subsets of epicardial progenitor cells for repair.

Expert opinion: The therapeutic potential of Tβ4 for the treatment of cardiac failure is herein evaluated alongside existing, emerging and prospective novel treatments.     

Recombinant FIXFc: a novel therapy for the royal disease?

INTRODUCTION: Hemophilia B, the deficiency or complete absence of coagulation factor IX (FIX), affects an estimated 80,000 people throughout the world. Some of these individuals are managed with prophylaxis, which involves the intravenous infusion of FIX concentrate two to three times weekly to prevent bleeding. Because FIX prophylaxis remains underutilized, patients with hemophilia B are at risk for bleeding that may be severe and potentially life- or limb-threatening, and they may experience arthropathy resulting from recurrent hemarthroses. AREAS COVERED: This review focuses on recent advances in therapeutic protein fusion technology as they apply to FIX deficiency. The National Library of Medicine Medline database was searched for articles containing the term 'Fc fusion proteins'. EXPERT OPINION: Genetically engineered recombinant FIX fused to the Fc portion of immunoglobulin significantly extends FIX half-life, thereby decreasing the frequency of prophylactic infusions. This in turn may increase the adoption of, and adherence to, prophylaxis, leading to better outcomes for hemophilia B patients.     

Human kallikrein 10: a novel tumor marker for ovarian carcinoma?

BACKGROUND: Human kallikrein 10 (hK10, encoded by KLK10 gene) is a recently discovered member of the human kallikrein family. hK10 is a secreted serine protease. With the development of a highly sensitive and specific immunoassay for hK10, quantification of hK10 in the circulation is now feasible. Our aim was to investigate whether hK10 concentration in serum changes in various malignancies. METHODS: We used a highly specific and sensitive immunofluorometric assay to quantify hK10 protein in 374 serum samples from healthy individuals and patients with various malignancies. RESULTS: Serum hK10 concentration was found to be significantly elevated in 56% of the ovarian cancer patients and such an increase was not observed in serum of healthy individuals or in serum of patients with other types of cancer, with the exception of approximately 15% of patients with gastrointestinal cancer. This hK10 elevation does not correlate well with CA 125. We have further demonstrated that hK10 concentration changes during ovarian cancer progression. CONCLUSION: This is the first report describing that hK10 serum concentration is significantly elevated in the majority of ovarian cancer patients. Our results indicate that hK10 may be a potential new serological marker for ovarian cancer diagnosis and monitoring.