Leukocyte ß-adrenergic receptor sensitivity and depression severity in patients with heart failure.

OBJECTIVES: Clinical outcomes are worse for patients with heart failure (HF) and elevated depression symptoms. Depression-related sympathoimmune dysregulation may be one mechanism leading to poorer HF prognosis. Sympathetically mediated adrenergic activity is known to regulate immune activity via ß-adrenergic receptors (ß-ARs). However, studies show conflicting relationships between leukocyte ß-AR sensitivity and depression symptoms. The aim of this study was to determine in patients with HF the relationship of leukocyte ß-AR sensitivity with two diverse measures of depression, self-report questionnaire versus clinical diagnostic interview. METHODS: Patients with HF (N = 73, mean [standard deviation] age = 56.3 [13.0]) completed the Beck Depression Inventory-1A and a modified Structured Clinical Interview for the DSM-IV. Leukocyte ß-AR sensitivity was determined from isoproterenol-stimulated cyclic adenosine monophosphate levels; plasma norepinephrine and epinephrine were also assessed. RESULTS: Patients with major depression determined by Structured Clinical Interview for the DSM-IV had significantly higher ß-AR sensitivity than did nondepressed patients (F(6,72) = 9.27, p = .003, η = 0.12). The Beck Depression Inventory-1A revealed a more complex relationship. Minimal, mild, and moderate-to-severe depression symptom groups had significant differences in ß-AR sensitivity (F(7,72) = 7.03, p = .002, η = 0.18); mild symptoms were associated with reduced ß-AR sensitivity and moderate-to-severe symptoms with higher ß-AR sensitivity compared with patients with minimal depressive symptoms. CONCLUSIONS: Clinical depression was associated with elevated ß-AR sensitivity in patients with HF. By deconstructing depression measurements, a greater depth of information may be garnered to potentially reveal subtypes of depression symptoms and their relation to ß-AR sensitivity.

Management of pediatric uveitis.

Pediatric uveitis is a topic of special interest not only because of the unique diagnostic and therapeutic challenges but also because of the lifetime burden of vision loss if the problem is not adequately treated, as well as the economic and psychological toll on the family. Often, uveitis in children is discovered as part of a routine eye exam; this silent, insidious inflammation can be difficult to treat and can lead to further complications if not handled skillfully. Corticosteroids have long been the mainstay of therapy; however, the significant associated side effects mandate a corticosteroid-sparing therapeutic regimen in pursuit of remission. In this review, we cover the therapeutic options for pediatric uveitis, specifically focusing on the most common non-infectious varieties, juvenile idiopathic arthritis-associated uveitis and pars planitis.

A comprehensive review and update on the biologic treatment of adult noninfectious uveitis: part II.

INTRODUCTION: Treatment of adult, noninfectious uveitis remains a major challenge for ophthalmologists around the world, especially in regard to recalcitrant cases. It is reported to comprise approximately 10% of preventable blindness in the USA. The cause of uveitis can be idiopathic or associated with infectious and systemic disorders. The era of biologic medical therapies provides new options for patients with otherwise treatment-resistant inflammatory eye disease. AREAS COVERED: This two-part review gives a comprehensive overview of the existing medical treatment options for patients with adult, noninfectious uveitis, as well as important advances for the treatment ocular inflammation. Part I covers classic immunomodulation and latest information on corticosteroid therapy. In part II, emerging therapies are discussed, including biologic response modifiers, experimental treatments and ongoing clinical studies for uveitis. EXPERT OPINION: The hazard of chronic corticosteroid use in the treatment of adult, noninfectious uveitis is well documented. Corticosteroid-sparing therapies, which offer a very favorable risk-benefit profile when administered properly, should be substituted. Although nothing is currently approved for on-label use in this indication, many therapies, through either translation or novel basic science research, have the potential to fill the currently exposed gaps.

A comprehensive review and update on the non-biologic treatment of adult noninfectious uveitis: part I.

INTRODUCTION: Treatment of adult, noninfectious uveitis remains a challenge for ophthalmologists around the world. The disease accounts for almost 10% of preventable blindness in the US and can be idiopathic or associated with infectious and systemic disorders. Strong evidence is still emerging to indicate that pharmacologic strategies presently used in rheumatologic or autoimmune disease may be translated to the treatment of intraocular inflammation. Corticosteroid monotherapy is widely regarded as wholly inappropriate, due to the unfavorable risk/benefit profile and poor long-term outcomes. Treatment plans have shifted away from low-dose, chronic corticosteroid therapy for maintenance, towards medium- to high-dose therapy for acute inflammation, followed immediately by initiation of immunomodulatory therapy. These therapies follow the 'stepladder approach', whereby least to more aggressive therapies are trialed to induce remission of inflammation, eventually without corticosteroids of any form (topical, local and systemic). AREAS COVERED: This two-part review gives a comprehensive overview of the existing medical treatment options for patients with adult, noninfectious uveitis, as well as important advances for the treatment of ocular inflammation. Part I covers classic immunomodulation and latest information on corticosteroid therapy. EXPERT OPINION: The hazard of chronic corticosteroid use for the treatment of adult, noninfectious uveitis is well-documented. Corticosteroid-sparing therapies, which offer a very favorable risk-benefit profile when administered properly, should be substituted.

Neutrophil gelatinase-associated lipocalin as diagnostic and prognostic tool for cardiovascular disease and heart failure.

INTRODUCTION: Cardiovascular disease (CVD) has been a burden on the healthcare system for decades and has increased the need for earlier diagnosis, better risk stratification and cost- effective treatment to reduce the rates of hospitalization. Biomarker research has broadened our knowledge base, shedding more light on the underlying pathophysiological mechanisms associated with the development of heart disorders. Recent technological advances have made it possible to use noninvasive and cost-effective biomarkers for identifying patients who are at risk of developing coronary heart disease and atherosclerosis. AREAS COVERED: In this paper the authors review the development of neutrophil gelatinase-associated lipocalin (NGAL) as a cardiac biomarker, highlighting studies that validate its use in predicting acute changes in patients with an array of cardiac disorders, and stake a case for the use of NGAL as a clinical diagnostic tool to predict outcomes in patients with CVD. EXPERT OPINION: The authors believe that NGAL should be used as a clinical diagnostic tool to predict outcomes in patients with CVD. Growing evidence has illustrated the biological role that neutrophils, such as NGAL, play in inflammation and atherosclerosis. Further studies are needed to determine NGAL's stability in serum and urine, and to substantiate its widespread use, but there are expanding possibilities for this biomarker in clinical practice.

Comparison of moderate and severe hospitalized Pediatric 2009 H1N1 influenza cases.

Since its discovery in 2009, H1N1 influenza (H1N1) has spread globally. Predictive factors for severe disease in children are not well defined. Our retrospective data collection and logistic regression analysis on 137 patients hospitalized between April 2009 and February 2010 at Children's Hospital and Research Center Oakland describe clinical and epidemiologic features of H1N1 in children and determines predictors of severe disease.

Post-traumatic stress disorder: a fast track to premature cardiovascular disease?

An increasing body of evidence reported in the literature indicates a possible role for post-traumatic stress disorder (PTSD) as a cause for cardiovascular disease (CVD). However, mechanistic evidence on the progression of adverse cardiac outcomes in PTSD is lacking. In this review, we examine the potential paths by which CVD could occur in those with PTSD. Dysregulation of the hypothalamic-pituitary-adrenal axis and autonomic nervous dysfunction are commonly observed in PTSD, which in turn leads to a variety of physiological changes potentially damaging to the heart. Increased inflammation, dysfunction of the vascular endothelium, hypercoagulability, and cardiac hyperreactivity all have been noted in patients with PTSD. Altered neurochemistry, most notably increased arginine vasopressin, as well as an increased prevalence of the metabolic syndrome, may also contribute to adverse cardiac outcomes. Although the association between PTSD and physical disease is often complicated by health risk behaviors or comorbid psychiatric conditions, the evidence for a link between PTSD and CVD is substantial. In our examination, we attempt to identify potential cardiac biomarkers that may be useful in detecting increased cardiac risk in patients with PTSD. As research in this area is exceedingly limited, we hope to inspire further research, as there is great potential value in identifying prognostically useful cardiac biomarkers so as to predict and prevent the onset of CVD in patients with PTSD.

Cardiac biomarkers: new tools for heart failure management.

The last decade has seen exciting advances in the field of biomarkers used in managing patients with heart failure (HF). Biomarker research has broadened our knowledge base, shedding more light on the underlying pathophysiological mechanisms occurring in patients with both acute and chronic HF. The criterion required by an ideal cardiovascular biomarker has been progressively changing to an era of sensitive assays that can be used to guide treatment. Recent technological advances have made it possible to rapidly measure even minute amounts of these proteins by means of higher sensitivity assays. With a high prevalence of comorbidities associated with HF, an integrated approach utilizing multiple biomarkers have shown promise in predicting mortality, better risk stratification and reducing re-hospitalizations, thus lowering health-care costs. This review provides a brief insight into recent advances in the field of biomarkers currently used in the diagnosis and prognosis of patients with acute and chronic HF.

Cardiac biomarkers, mortality, and post-traumatic stress disorder in military veterans.

Post-traumatic stress disorder (PTSD) is gaining increasing recognition as a risk factor for morbidity and mortality. The aim of this study was to examine the impact of PTSD and abnormal cardiovascular biomarkers on mortality in military veterans. Eight hundred ninety-one patients presenting for routine echocardiography were enrolled. Baseline clinical data and serum samples for biomarker measurement were obtained and echocardiography was performed at the time of enrollment. Patients were followed for up to 7.5 years for the end point of all-cause mortality. Ninety-one patients had PTSD at the time of enrollment. There were 33 deaths in patients with PTSD and 221 deaths in those without PTSD. Patients with PTSD had a trend toward worse survival on Kaplan-Meier analysis (p = 0.057). Among patients with elevated B-type natriuretic peptide (>60 pg/ml), those with PTSD had significantly increased mortality (p = 0.024). Among patients with PTSD, midregional proadrenomedullin (MR-proADM), creatinine, and C-terminal proendothelin-1 were significant univariate predictors of mortality (p = 0.006, p = 0.024, and p = 0.003, respectively). In a multivariate model, PTSD, B-type natriuretic peptide, and MR-proADM were independent predictors of mortality. In patients with PTSD, MR-proADM was a significant independent predictor of mortality after adjusting for B-type natriuretic peptide, cardiovascular risk factors, cancer, and sleep apnea. Adding MR-proADM to clinical predictors of mortality increased the C-statistic from 0.572 to 0.697 (p = 0.007). In conclusion, this study demonstrates an association among PTSD, abnormal cardiac biomarker levels, and increased mortality.