The Added Value of Exercise Variables in Heart Failure Prognosis.

INTRODUCTION: Diminished exercise capacity is a key symptom in heart failure (HF). Exercise predictors (peak VO2, VE/VCO2 slope, and oxygen uptake efficiency slope [OUES]) are prognostic markers but studied in isolation. We evaluated if these exercise variables offer additional prognostic value to clinical predictors in HF. METHODS AND RESULTS: This was a single-institution retrospective cohort study of 517 consecutive HF patients. We used Cox proportional hazards modeling to determine the additional prognostic value of exercise variables on mortality, HF hospital admissions, and a composite outcome of ventricular assistance device (VAD) implantation, heart transplantation (HT), and death. During a mean follow-up of 2.7 years, 52 deaths, 47 HTs, and 19 VAD implantations occurred. After adjusting for age, New York Heart Association functional class, ejection fraction, body mass index, creatinine, and B-type natriuretic peptide, peak VO2 (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.85-0.96), OUES (HR 0.92, 95% CI 0.87-0.97), and VE/VCO2 (HR 1.03, 95% CI 1.01-1.05) were independent predictors of the composite outcome. Similar discriminatory capacity existed between the exercise variables (c-statistics 0.77, 0.78, and 0.78, respectively). Only VE/VCO2 was an independent predictor of admissions (HR 1.04, 95% CI 1.01-1.07), and only peak VO2 was an independent predictor of mortality (HR 0.90, 95% CI 0.84-0.98). CONCLUSIONS: Peak VO2, OUES, and VE/VCO2 are independent predictors of HF prognosis over recognized clinical variables. However, no single exercise variable was superior.

Right ventricular function and prognosis in stable heart failure patients.

BACKGROUND: Right ventricular ejection fraction (RVEF) is a mortality predictor in heart failure (HF) patients. There are controversial results regarding the influence of RVEF on other important prognostic variables. The purpose of this study was to investigate the effect of RVEF on exercise parameters obtained during cardiopulmonary exercise testing (CPET), creatinine and B-type natriuretic peptide (BNP) levels, and a composite outcome of death, heart transplantation, or ventricular assist device implantation in ambulatory HF patients. METHODS AND RESULTS: This retrospective cohort study included 246 ambulatory HF patients with CPET and RVEF evaluated with the use of first-pass radionuclide angiography. We analyzed the impact of RVEF on other prognostic factors with the use of multivariable linear regression. The mean age was 49 ± 12 years. The mean peak VO2 was 16.4 ± 5.7 mL kg(-1) min(-1), mean peak VE/VCO2 34.1 ± 9.1, mean creatinine 1.17 ± 0.40 mg/dL, and median BNP 158 pg/mL (interquartile range 374 pg/mL). The mean left ventricular ejection fraction was 35 ± 12% and the mean RVEF 38 ± 10%. For every 10% decrease in RVEF, peak VO2 decreased 0.97 mL kg(-1) min(-1) (P < .05), creatinine increased 0.12 mg/dL (P < .01), and log BNP increased 0.26 (P < .05). CONCLUSIONS: We found an independent association between RVEF and prognostic markers in HF patients. Worsening RV function may exert its negative effect on prognosis through increasing congestion (elevated BNP), affecting renal blood flow (increased creatinine) and limiting left ventricular preload, thereby reducing exercise tolerance.

Neuroanatomical characterisation of the expression of the lipodystrophy and motor-neuropathy gene Bscl2 in adult mouse brain.

The endoplasmic reticulum localised protein seipin, encoded by the gene Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2), serves a critical but poorly defined function in the physiology of both adipose and neural tissue. In humans, BSCL2 loss-of-function mutations cause a severe form of lipodystrophy, whilst a distinct set of gain-of-toxic-function mutations are associated with a heterogeneous group of neuropathies. However, despite the importance of seipin dysfunction to the pathophysiology of these conditions, little is known about its physiological role in adipocytes or neurons. BSCL2 mRNA has previously been identified in human and mouse brain, yet no definitive assessment of its expression has been undertaken. Here we comprehensively characterised the neuroanatomical distribution of mouse Bscl2 using complementary in situ hybridisation histochemistry and immunohistochemistry techniques. Whilst Bscl2 was broadly expressed throughout the rostral-caudal extent of the mouse brain, it exhibited a discrete neuroanatomical profile. Bscl2 was most abundantly expressed in the hypothalamus and in particular regions associated with the regulation of energy balance including, the paraventricular, ventromedial, arcuate and dorsomedial nuclei. Bscl2 expression was also identified within the brainstem dorsal vagal complex, which together with the paraventricular nucleus of the hypothalamus represented the site of highest expression. Further neurochemical profiling of these two nuclei revealed Bscl2/seipin expression within energy balance related neuronal populations. Specifically, seipin was detected in oxytocin neurons of the paraventricular nucleus of the hypothalamus and in catecholamine neurons of the dorsal vagal complex. These data raise the possibility that in addition to its role in adipose tissue development, seipin may also be involved in the central regulation of energy balance.

Coronaviral hypothetical and structural proteins were found in the intestinal surface enterocytes and pneumocytes of severe acute respiratory syndrome (SARS).

Severe acute respiratory syndrome (SARS) is a newly emerging infectious disease that haunted the world from November 2002 to July 2003. Little is known about the biology and pathophysiology of the novel coronavirus that causes SARS. The tissue and cellular distributions of coronaviral hypothetical and structural proteins in SARS were investigated. Antibodies against the hypothetical (SARS 3a, 3b, 6, 7a and 9b) and structural proteins (envelope, membrane, nucleocapsid and spike) of the coronavirus were generated from predicted antigenic epitopes of each protein. The presence of these proteins were first verified in coronavirus-infected Vero E6 tissue culture model. Immunohistochemical studies on different human tissues, including a cohort of nine autopsies, two liver biopsies and intestinal biopsies of SARS patients, further confirmed the existence of coronaviral hypothetical and structural proteins in the cytoplasm of pneumocytes and small intestinal surface enterocytes in SARS patients. With this vast array of antibodies, no signal was observed in other cell types including those organs in which reverse transcriptase-polymerase chain reactions were reported to be positive. Structural proteins and the functionally undefined hypothetical proteins were expressed in coronavirus-infected cells with distinct expression pattern in different organs in SARS patients. These antipeptide antibodies can be useful for the diagnosis of SARS at the tissue level.

AKT plays a role in the survival of the tumor cells of extranodal NK/T-cell lymphoma, nasal type.

Phosphorylated AKT has been detected in extranodal NK/T-cell lymphoma, nasal type (ENTL). Either interleukin-2 (IL-2) or interleukin-15 (IL-15) could prevent AKT dephosphorylation and apoptosis in the NK-92 cell line model. IL-15, but not IL-2, was preferentially elevated in patients' serum. AKT and IL-15 may be important in ENTL tumor survival.