Recoverable cognitive dysfunction at hospital admission in older persons during acute illness

BACKGROUND: While acute illness and hospitalization represent pivotal events for older persons, their contribution to recoverable cognitive dysfunction (RCD) has not been well examined. OBJECTIVE: Our goals were to estimate the frequency and degree of RCD in an older hospitalized cohort; to examine the relationship of RCD with delirium and dementia; and to determine 1-year cognitive outcomes. DESIGN: Prospective cohort study. PARTICIPANTS: Four hundred and sixty patients aged > or =70 years drawn from consecutive admissions to an academic hospital. MEASUREMENTS: Patients underwent interviews daily during hospitalization and at 1 year. The primary outcome was RCD, defined as an admission Mini-Mental State Examination (MMSE) score that improved by 3 or more points by discharge. RESULTS: Recoverable cognitive dysfunction occurred in 179 of 460 (39%) patients, with MMSE impairment at baseline ranging from 3 to 13 points (median=5.0 points). The majority of cases were not characteristic of either delirium or dementia, as 144 of 179 (80%) cases did not meet criteria for delirium, and 133 of 164 (81%) cases did not meet criteria for dementia at baseline. In multivariable analysis controlling for baseline MMSE level, 3 factors were predictive of RCD: higher educational level, preadmission functional impairment, and higher illness severity. At 1 year, further improvement in MMSE score occurred in 38 of 92 (41%) patients with RCD. Recoverable cognitive dysfunction was independently predictive of 1-year mortality with an adjusted odds ratio of 1.82 (95% confidence interval [95% CI] 1.03 to 3.20). CONCLUSIONS: Acute illness is accompanied by a high rate of RCD that is neither characteristic of delirium or dementia. Our observations underscore the reversible nature of this cognitive dysfunction with continued improvement over the ensuing year, and highlight the potential clinical implications of this under-recognized phenomenon.     

Identification of sokotrasterol sulfate as a novel proangiogenic steroid

The potential to promote neovascularization in ischemic tissues using exogenous agents has become an exciting area of therapeutics. In an attempt to identify novel small molecules with angiogenesis promoting activity, we screened a library of natural products and identified a sulfated steroid, sokotrasterol sulfate, that induces angiogenesis in vitro and in vivo. We show that sokotrasterol sulfate promotes endothelial sprouting in vitro, new blood vessel formation on the chick chorioallantoic membrane, and accelerates angiogenesis and reperfusion in a mouse hindlimb ischemia model. We demonstrate that sulfation of the steroid is critical for promoting angiogenesis, as the desulfated steroid exhibited no endothelial sprouting activity. We thus developed a chemically synthesized sokotrasterol sulfate analog, 2beta,3alpha,6alpha-cholestanetrisulfate, that demonstrated equivalent activity in the hindlimb ischemia model and resulted in the generation of stable vessels that persisted following cessation of therapy. The function of sokotrasterol sulfate was dependent on cyclooxygenase-2 activity and vascular endothelial growth factor induction, as inhibition of either cyclooxygenase-2 or vascular endothelial growth factor blocked angiogenesis. Surface expression of alpha(v)beta(3) integrin was also necessary for function, as neutralization of alpha(v)beta(3) integrin, but not beta(1) integrin, binding abrogated endothelial sprouting and antiapoptotic activity in response to sokotrasterol sulfate. Our findings indicate that sokotrasterol sulfate and its analogs can promote angiogenesis in vitro and in vivo and could potentially be used for promoting neovascularization to relieve the sequelae of vasoocclusive diseases.     

Determinants of platelet count in pediatric patients with congenital cyanotic heart disease: Role of immature platelet fraction

Objectives

Congenital heart defects are common noninfectious causes of mortality in children. Bleeding and thrombosis are both limiting factors in the management of such patients. We assessed the frequency of thrombocytopenia in pediatric patients with congenital cyanotic heart disease (CCHD) and evaluated determinants of platelet count including immature platelet fraction (IPF) and their role in the pathogenesis of thrombocytopenia.

Methods

Forty‐six children and adolescents with CCHD during pre‐catheter visits were studied; median age was 20.5 months. Complete blood count including IPF as a marker of platelet production and reticulated hemoglobin content (RET‐He) as a marker of red cell production and iron status were done on Sysmex XE 2100 (Sysmex, Japan). C‐reactive protein, prothrombin time (PT), Activated partial thromboplastin time (APTT) were also assessed.

Results

Thrombocytopenia was found in 6 patients (13%). PT was prolonged (P = .016) and IPF was significantly higher in patients with thrombocytopenia compared with patients with normal platelet count (14.15 ± 5.2% vs 6.68 ± 3.39%; P = .003). Platelet count was negatively correlated with IPF while significant positive correlations were found between IPF and hemoglobin, red blood cells (RBCs) count, hematocrit (Hct), PT, reticulocytes count, and immature reticulocyte fraction.

Conclusions

We suggest that elevated IPF in CCHD patients with thrombocytopenia may denote peripheral platelets destruction as an underlying mechanism. Hemoglobin level, RBCs count, Hct, and RET‐He were not significant determinants for platelet count in CCHD.     

Role of echocardiography in reducing shock reversal time in pediatric septic shock: a randomized controlled trial

Objective

To evaluate the role of echocardiography in reducing shock reversal time in pediatric septic shock.