Plasma Glial Fibrillary Acidic Protein in the Differential Diagnosis of Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Plasma GFAP (glial fibrillary acidic protein) has recently emerged as a potential biomarker for the differentiation of acute intracerebral hemorrhage (ICH) from acute ischemic stroke (AIS). We prospectively assessed the diagnostic accuracy of GFAP in the differential diagnosis of ICH. METHODS: Consecutive patients presenting to the emergency department within 6 hours from symptom onset were evaluated. All patients underwent extensive diagnostic work-up and were classified according to discharge diagnosis in AIS, ICH, subarachnoid hemorrhage, and stroke mimics. GFAP was also measured in healthy volunteers (controls). Baseline stroke severity was evaluated using National Institutes of Health Stroke Scale. Receiver operating characteristic curve analysis was used to identify the optimal cutoff point for the differentiation between subgroups. Correlation analyses of GFAP plasma concentrations with baseline National Institutes of Health Stroke Scale and onset to sampling time were performed with the nonparametric Spearman rank test and fractional polynomial regression, respectively. RESULTS: Our study population consisted of 270 individuals (AIS: 121, ICH: 34, stroke mimics: 31, subarachnoid hemorrhage: 5, controls: 79). No differences on baseline stroke severity and onset to sampling time were detected between AIS and ICH. Higher median plasma GFAP values were documented in ICH compared with AIS, stroke mimics, and controls (P<0.001). Receiver operating characteristic analysis highlighted a cutoff value of 0.43 ng/mL as the optimal threshold for the differentiation between ICH and AIS (sensitivity: 91%, specificity: 97%). No association was detected between plasma GFAP concentrations and baseline stroke severity for both AIS (P=0.515) and ICH (P=0.387). In the fractional polynomial analysis, the association between GFAP concentration and onset to sampling time was best described by a J-shaped curve for AIS and an inverted U-shaped curve for ICH, with a peak at 2 hours. CONCLUSIONS: Plasma GFAP seems to be a sensitive and specific biomarker for the differentiation of ICH from both AIS and other acute neurological disorders, with the optimal diagnostic yield being present in the second hour from symptom onset.

Prognostic significance of serum albumin level changes in acute ischemic stroke: the role of biological and analytical variation.

BACKGROUND: Animal studies have shown a neuroprotective effect of human serum albumin (sAlb) in ischemic stroke (IS). Previous studies have shown an association of high sAlb with better outcome. Our aim is to investigate the kinetics of sAlb in acute IS and its possible correlation with outcome taking into account the analytical and biological variation of sAlb measurement. METHODS: In a prospective observational study, we enrolled 105 patients with acute IS. sAlb was measured upon admission, at 24 h, 48 h, 72 h and Day 7 thereafter. Stroke severity was assessed upon admission and at 72 h, and functional outcome on Day 7. Patients were divided into two groups according to functional outcome on discharge. Calculation of reference change value was used to assess the clinical significance of sAlb changes and multiple logistic regression to assess the independent association between variables and outcome. RESULTS: Fifty-one patients (48.6%) had poor outcome. Their sAlb levels exhibit a significant daily decrease until 72 h (35.9 g/L) compared to baseline (41.1 g/L) and remained low until Day 7 (36.0 g/L). These changes were clinically significant only from 72 h on. Among non-poor outcome patients a significant daily decrease until 72 h (40.9 g/L) was followed by recovery on Day 7 (41.2 g/L), but these changes were not clinically significant. sAlb was not independently associated with the functional outcome at any time-point. CONCLUSIONS: This study shows that sAlb levels might change during the first days after an acute IS, but these changes although statistically significant are not clinically significant if we take into account the analytical and biological variation of sAlb.

Effect of green tea on postprandial antioxidant capacity, serum lipids, C-reactive protein and glucose levels in patients with coronary artery disease.

PURPOSE: Cardiovascular risk factors have been identified in the postprandial state, particularly in patients with coronary artery disease (CAD). Tea consumption has been linked to cardiovascular risk reduction, but the beneficial effect of tea has not been investigated under postprandial conditions. The objective was to examine the effect of green tea on postprandial levels of plasma total antioxidant capacity (TAC), serum lipids, C-reactive protein (CRP) and glucose in patients with CAD. METHODS: In a randomized controlled, parallel design with 2 arms, 43 patients with CAD were assigned to consume breakfast consisting of bread, butter and 330 ml water or tea (4.5 g green tea/330 ml, providing approximately 400 mg catechins). Blood samples were drawn immediately before and 1.5, 3 and 5 h after breakfast. TAC was measured in plasma with the ferric reducing antioxidant power of plasma and oxygen radical absorbance capacity assays. Total cholesterol, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglycerides, glucose, CRP, uric acid and pancreatic lipase levels were measured in serum. RESULTS: Tested biomarkers did not differ between tea and water group at baseline, 1.5, 3 and 5 h (P > 0.05) postprandially. However, TAC increased 1.5 and 3 h after consumption of breakfast with tea (P < 0.005), but no change was observed after consumption of breakfast with water. Serum triglycerides levels significantly increased 3 h after breakfast with water (P = 0.031), but not after breakfast with tea. Serum uric acid decreased 1.5 h after breakfast with tea (P = 0.038). Pancreatic lipase, CRP, total cholesterol, HDL-C, LDL-C and glucose levels remained unchanged after breakfast with tea at any time point (P > 0.05). CONCLUSIONS: Tea consumption did not affect selected biomarkers at any postprandial time point in patients with CAD.

Atrial fibrillation post CABG and the risk of arrhythmia recurrence: the AFRODITE study.

BACKGROUND: New-onset postoperative atrial fibrillation (POAF) after coronary artery bypass surgery (CABG) occurs with an incidence of 20-40%. The clinical relevance of POAF remains a concern, and the need for further studies regarding the clinical management of POAF is necessary. AIM: The AFRODITE study, a prospective multicenter cohort study, had as its primary endpoint the evaluation of AF recurrence in patients post CABG over a one-year period. METHODS: Two hundred twenty-eight patients aged >50 years who underwent isolated CABG were included in the study. Patients were stratified into two groups, POAF and non-POAF, and followed for 12 months for AF recurrence, hospitalizations, and death. RESULTS: Two hundred twenty-eight patients (mean age 67 years, 88.6% male) were included in the study. 28.5% of patients experienced at least one episode of POAF during index hospitalization (POAF group) and were compared with the non-POAF group (n = 163). Multivariate stepwise logistic regression analysis showed that the strongest prognostic parameter for POAF was the CHA2DS2-VASc score (odds ratio = 1.61, p < 0.001). POAF patients had a worse in-hospital outcome, but the incidence of long-term AF recurrence was not statistically different (3.6% vs. 4.8%, p = 0.9). CONCLUSION: Interestingly, a one-year prospective follow-up of patients in the study did not reveal significant differences between POAF and non-POAF patients. A notable finding was that patients with a higher CHA2DS2-VASc score were more likely to develop POAF.

Treating volume overload in acutely decompensated heart failure: established and novel therapeutic approaches.

BACKGROUND: Most patients hospitalized for acutely decompensated heart failure (ADHF) present with symptoms and signs of volume overload, which is also associated with substantially high rates of death and rehospitalization in ADHF. OBJECTIVE: To review the recent experimental and clinical evidence on existing therapeutic algorithms and investigational drugs used for the treatment of volume overload in ADHF patients. METHODS: A systematic search of peer-reviewed publications was performed on Medline and EMBASE from January 1990 to March 2012. The results of unpublished trials were obtained from presentations at national and international meetings. RESULTS: Apart from intrinsic renal insufficiency and neurohormonal activation, volume overload through venous congestion may be the primary haemodynamic factor triggering the worsening of renal function in ADHF patients. It is well known that heart and kidneys are closely interrelated and an acute or chronic disorder in one organ may induce acute or chronic dysfunction in the other organ. Established therapeutic strategies, (e.g. loop diuretics, vasodilators, and inotropes), are sometimes associated with limited clinical success due to tolerance and the need for frequent up titration of the doses in order to achieve the desired effect. That leads to an increasing interest in novel options, such as the use of adenosine A1 receptor antagonists, vasopressin antagonists, and renal-protective dopamine. Initial clinical trials have shown quite encouraging results in some heart failure subpopulations but have failed to demonstrate a clear beneficial role of these agents. On the other hand, ultrafiltration appears to be a more promising therapeutic procedure that will improve volume regulation, while preserving renal and cardiac function. CONCLUSION: Further clinical studies are required in order to determine their net effect on renal function and potential cardiovascular outcomes. Until then, management of volume overload in ADHF patients remains a challenge for the clinicians.

Intraabdominal desmoplastic small round cell tumor: Report of a case and literature review.

INTRODUCTION: Desmoplastic small round cell tumor is a rare malignancy with poor prognosis that predominantly affects young males. Its etiopathogenesis is still unknown and diagnosis can be achieved only by immunohistochemistry and cytogenetic studies. Due to our limited knowledge of the pathologic and clinical nature of this disease, there is no clear consensus regarding the optimal therapeutic procedures for treating this neoplasm. A high degree of care and improvements in diagnostic capabilities are required in order to identify this entity and avoid misdiagnosis. CASE PRESENTATION: We report a new case of a 29-year-old male who proceeded to our Emergency Department complaining about non-specific abdominal pain. Physical examination revealed no abnormalities except for a palpable mass in the lower abdomen and a diffuse abdominal pain. Computed Tomography scan showed enlarged paraortic and mesenteric lymphadenopathy, thickness of the small bowel wall and dispersed masses intraperitoneally. He underwent an exploratory laparotomy and the resultant biopsy revealed desmoplastic small round cell tumor. DISCUSSION: Diagnosis of desmoplastic small round cell tumor can easily be missed because it presents with few early warning symptoms and signs, while the routine blood tests are within normal limits. CONCLUSION: A high degree of suspicion, a thorough physical examination, a full imaging check and an aggressive therapeutic approach are required in order to identify this disease and fight for a better quality of life for these patients. In addition we make a review of the literature in an effort to clarify the epidemiological, clinical and pathological aspects of this entity.

Combined effects of atorvastatin and metformin on glucose-induced variations of inflammatory process in patients with diabetes mellitus.

BACKGROUND: Statin treatment improves survival in patients with atherosclerosis, but their effect on the glucose-induced variations of inflammatory markers, is unknown. We examined the effect of combined therapy with atorvastatin and metformin on glucose-induced variations of inflammatory molecules in patients with newly diagnosed diabetes mellitus type 2 (DM). METHODS: Thirty five subjects with newly diagnosed DM were randomized to receive metformin 850 mg/d (M, n=17) or metformin 850 mg/d+atorvastatin 10mg (n=18). All subjects underwent glucose loading (75 g oral glucose) at baseline and after 12 weeks of treatment. Blood samples were obtained at baseline and 3h post-loading, while serum tumor necrosis factor alpha (TNF-α) levels were determined at baseline and at 3h. RESULTS: Serum TNF-α remained unchanged in metformin at baseline (1.36±0.18 to 1.47±0.21 pg/ml p=NS) and after treatment (1.44±0.71 to 1.31±0.17 pg/ml, p=NS), while it was reduced in metformin+atorvastatin (2.3±0.3 to 2.0±0.4 pg/ml, p=NS at baseline and 1.80±0.2 to 1.65±0.2 pg/ml, p=0.03 after treatment). CONCLUSIONS: Interestingly, the combination of metformin and atorvastatin partly prevents the glucose-loading induced elevation of glucose levels (at 1 h), suggesting a better response to glucose intake than monotherapy with metformin. In addition, combined treatment with atorvastatin and metformin reduces the post-glucose loading levels of TNF-α compared to metformin monotherapy.

Therapeutic options for the management of the cardiorenal syndrome.

Patients with heart failure often present with impaired renal function, which is a predictor of poor outcome. The cardiorenal syndrome is the worsening of renal function, which is accelerated by worsening of heart failure or acute decompensated heart failure. Although it is a frequent clinical entity due to the improved survival of heart failure patients, still its pathophysiology is not well understood, and thus its therapeutic approach remains controversial and sometimes ineffective. Established therapeutic strategies, such as diuretics and inotropes, are often associated with resistance and limited clinical success. That leads to an increasing concern about novel options, such as the use of vasopressin antagonists, adenosine A1 receptor antagonists, and renal-protective dopamine. Initial clinical trials have shown quite encouraging results in some heart failure subpopulations but have failed to demonstrate a clear beneficial role of these agents. On the other hand, ultrafiltration appears to be a more promising therapeutic procedure that will improve volume regulation, while preserving renal and cardiac function. Further clinical studies are required in order to determine their net effect on renal function and potential cardiovascular outcomes. Until then, management of the cardiorenal syndrome remains quite empirical.

Impact of 6 weeks of treatment with low-dose metformin and atorvastatin on glucose-induced changes of endothelial function in adults with newly diagnosed type 2 diabetes mellitus: A single-blind study.

BACKGROUND: Statin treatment has been reported to improve survival in patients with atherosclerosis, partly by improving vascular endothelial function. Elevation of blood glucose concentrations impairs endothelial function and promotes atherogenesis, but the effect of statins on glucose-induced endothelial dysfunction is unknown. Endothelium-dependent dilation (EDD) measured by gauge-strain plethysmography in the forearm is considered to be a reliable marker of endothelial function in forearm resistance vessels. OBJECTIVE: This study examined the combined effects of metformin and atorvastatin treatment on glucose-induced endothelial dysfunction (as EDD) in patients with newly diagnosed type 2 diabetes mellitus (DM). METHODS: Patients with newly diagnosed DM were recruited and were randomly assigned to receive metformin 850 mg/d or metformin 850 mg/d + atorvastatin 10 mg/d for 6 weeks in a single-blind study. All patients underwent glucose loading (75 g oral glucose after 12 hours of fasting) at baseline and at the end of the treatment period. Blood samples were obtained at baseline before glucose loading and 3 hours after loading to determine serum concentrations of cholesterol, lipoproteins, triglycerides, glucose, and glycosylated hemoglobin. EDD was evaluated at baseline and at 1, 2, and 3 hours after loading. The investigators were blinded to the treatment group assignments, and all analyses were performed in a blinded manner. Adverse events (eg, gastrointestinal disorders, myopathy, liver disorders) were monitored based on reported symptoms or signs (eg, myalgias, muscle cramps), clinical examination, and laboratory parameters (eg, increased liver and muscle enzymes). RESULTS: Thirty-two white patients with newly diagnosed type 2 DM were randomly assigned to receive metformin 850 mg/d (n = 17 [12 men]; mean [SD] age, 53.88 [45] years; body mass index [BMI], 28.7 [4.5] kg/m²) or metformin 850 mg/d + atorvastatin 10 mg/d (n = 15 [6 men]; mean age, 52.53 [37] years; BMI, 28.5 [2.1] kg/m²). At baseline, EDD was reduced 1 and 2 hours after glucose loading in both study groups (P < 0.01). Glucose loading was associated with an elevation of blood glucose concentrations at 1 and 2 hours (P < 0.01 vs resting levels before loading), and concentrations returned to resting levels at 3 hours, in both groups at baseline and after treatment. Metformin alone or in combination with atorvastatin was associated with a significant reduction in resting glucose concentrations after 6 weeks (both, P < 0.05 vs baseline), but only the combination of metformin + atorvastatin partly prevented the glucose-induced elevation of serum glucose at 1 hour after loading and the glucose-induced decrease in EDD (both, P < 0.01 vs baseline). CONCLUSIONS: Glucose loading blunted endothelial function, with a deterioration in EDD, in these patients with newly diagnosed type 2 DM. However, combined treatment with metformin and atorvastatin for 6 weeks partly prevented the glucose-induced impairment of EDD in these patients, with a significant difference compared with monotherapy with metformin.

Common community infections and the risk for coronary artery disease and acute myocardial infarction: evidence for chronic over-expression of tumor necrosis factor alpha and vascular cells adhesion molecule-1.

BACKGROUND: Although several common community infections have been associated with the risk for coronary artery disease (CAD), their role in the development of acute myocardial infarction (AMI) is still unclear. We examined the prevalence of IgG and IgM (or IgA) antibodies against common infections such as HSV, Hepatitis A (HAV), Helicobacter pylori (HP), cytomegalovirus (CMV) and Chlamydia pneumoniae (CP), in CAD and AMI patients, and their relationship with pro-atherogenic inflammatory molecules. METHODS: A total number of 337 subjects were included in this study: 150 patients with angiographically documented stable CAD, 138 patients admitted with AMI and 49 healthy individuals. Serum IgG and IgM against HAV, CMV and HSV, IgG against HP and IgG/IgA against CP were determined in all participants. Serum tumor necrosis factor alpha (TNF-alpha) and soluble vascular cells adhesion molecule (sVCAM-1), were determined by ELISA. RESULTS: Patients with CAD were more likely to have anti-HAV IgG (94.4%), anti-HSV IgG (97.2%) and anti-HP IgG (55.1%) compared to healthy individuals (70.8%, 89.6% and 39.6% respectively, p<0.05 for all). In multivariate analysis, anti-HAV IgG was an independent predictor of CAD (beta(SE): 0.187(0.075), p=0.015). Among the CAD patients, the presence of anti-CP IgA was more frequent in those admitted with AMI (39%) compared to those with stable CAD (21%, p<0.05). Finally, both patients and controls had significantly higher levels of sVCAM-1 and TNF-alpha in the presence of anti-HAV IgG, compared to those without anti-HAV IgG (p<0.05 for all). CONCLUSION: Past infections with HAV, HSV and HP are associated with higher risk for coronary atherosclerosis, while the presence of anti-HAV IgG is also associated with higher levels of TNF-alpha and sVCAM-1. Furthermore, the presence of recent infection by CP is associated with higher risk for AMI among CAD patients. These findings are important since they demonstrate that past HAV, HSV and HP infections may affect cardiovascular risk, while recent CP infection may be implicated in the triggering of AMI among CAD patients.