Plasma levels of procalcitonin and eight additional inflammatory molecules in febrile neutropenic patients

OBJECTIVE:

This study aimed to examine the association between different inflammatory markers and specific clinical endpoints in patients with febrile neutropenia.

METHOD:

We prospectively evaluated the expression of procalcitonin (PCT), interleukin 8 (IL-8), induced protein-10, tumor necrosis factor alpha (TNF-α), two soluble TNF-α receptors (sTNF-R I and sTNF-R II), monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1 alpha, and eotaxin in 37 episodes of febrile neutropenia occurring in 31 hospitalized adult onco-hematologic patients. Peripheral blood samples were collected in the morning at inclusion (day of fever onset) and on days 1, 3, and 7 after the onset of fever. Approximately 2–3 ml of plasma was obtained from each blood sample and stored at -80°C.

RESULTS:

The sTNF-R II level at inclusion (day 1), the PCT level on the day of fever onset, and the change (day 3 - day 1) in the IL-8 and eotaxin levels were significantly higher in patients who died during the 28-day follow-up. A requirement for early adjustment of antimicrobial treatment was associated with higher day 3 levels of IL-8, sTNF-R II, PCT, and MCP-1.

CONCLUSION:

Procalcitonin, sTNF-R II, IL-8, MCP-1, and eotaxin could potentially be used to assess the risk of death and the requirement for early adjustment of antimicrobial treatment in febrile, neutropenic onco-hematologic patients. The levels of the other markers showed no association with any of the evaluated endpoints.     

Immunogenicity of influenza H1N1 vaccination in mixed connective tissue disease: effect of disease and therapy

OBJECTIVE:

To assess the potential acute effects regarding the immunogenicity and safety of non-adjuvanted influenza A H1N1/2009 vaccine in patients with mixed connective tissue disease and healthy controls.

METHODS:

Sixty-nine mixed connective tissue disease patients that were confirmed by Kasukawa''s classification criteria and 69 age- and gender-matched controls participated in the study; the participants were vaccinated with the non-adjuvanted influenza A/California/7/2009 (H1N1) virus-like strain. The percentages of seroprotection, seroconversion, geometric mean titer and factor increase in the geometric mean titer were calculated. The patients were clinically evaluated, and blood samples were collected pre- and 21 days post-vaccination to evaluate C-reactive protein, muscle enzymes and autoantibodies. Anti-H1N1 titers were determined using an influenza hemagglutination inhibition assay. ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT01151644","term_id":"NCT01151644"}}NCT01151644.

RESULTS:

Before vaccination, no difference was observed regarding the seroprotection rates (p = 1.0) and geometric mean titer (p = 0.83) between the patients and controls. After vaccination, seroprotection (75.4% vs. 71%, p = 0.7), seroconversion (68.1% vs. 65.2%, p = 1.00) and factor increase in the geometric mean titer (10.0 vs. 8.0, p = 0.40) were similar in the two groups. Further evaluation of seroconversion in patients with and without current or previous history of muscle disease (p = 0.20), skin ulcers (p = 0.48), lupus-like cutaneous disease (p = 0.74), secondary Sjögren syndrome (p = 0.78), scleroderma-pattern in the nailfold capillaroscopy (p = 1.0), lymphopenia ≤1000/mm³ on two or more occasions (p = 1.0), hypergammaglobulinemia ≥1.6 g/d (p = 0.60), pulmonary hypertension (p = 1.0) and pulmonary fibrosis (p = 0.80) revealed comparable rates. Seroconversion rates were also similar in patients with and without immunosuppressants. Disease parameters, such as C-reactive protein (p = 0.94), aldolase (p = 0.73), creatine phosphokinase (p = 0.40) and ribonucleoprotein antibody levels (p = 0.98), remained largely unchanged pre and post-vaccination. No severe side effects were reported.

CONCLUSIONS:

The non-adjuvanted influenza A/H1N1 vaccination immune response in mixed connective tissue disease patients is adequate and does not depend on the disease manifestations and therapy.     

Reduced plasma adiponectin levels relative to oxidized low density lipoprotein and nitric oxide in coronary artery disease patients

INTRODUCTION:

Adiponectin is a circulating hormone that is produced exclusively by adipocytes and has anti-inflammatory and anti-atherogenic properties. The hypothesis that there are differences in adiponectin levels between stable and unstable coronary-artery disease patients remains controversial. Furthermore, the potential relationships between the plasma adiponectin level and the inflammatory and non-inflammatory markers (oxidized low density lipoprotein and nitric oxide) in patients with stable and unstable coronary-artery disease relative to normal subjects have not been assessed.

OBJECTIVES:

To assess whether plasma adiponectin levels differ among patients with stable and unstable coronary-artery disease and among control subjects, and to correlate plasma adiponectin level with inflammatory and clinical risk factors (such as oxidized-LDL and nitric oxide) in these patients.

METHODS:

This study included 50 control subjects, 50 stable angina patients and 50 unstable angina patients with angiographically documented coronary-artery disease. Plasma adiponectin and oxidized-LDL levels were determined using an enzyme immunoassay. Plasma nitric oxide, high sensitivity C-reactive protein and lipid profile levels were also measured.

RESULTS:

Plasma adiponectin levels were lower in the unstable angina patients (4.9±1.30 µg/mL) than in the stable angina patients (6.34±1.0 µg/mL) or in the controls (9.25±1.8 µg/mL); these levels were also significantly lower in stable angina patients versus controls (p<0.001). Plasma adiponectin levels were negatively correlated with oxidized-LDL, high sensitivity C-reactive protein, lipid profile and other clinical risk factors but positively correlated with nitric oxide.

CONCLUSION:

Plasma adiponectin levels were found to be lower in both stable and unstable angina patients relative to control subjects, and the correlation between plasma adiponectin and cardiovascular markers is weakened in these patients.     

C-Reactive protein predicts acute myocardial infarction during high-risk noncardiac and vascular surgery

BACKGROUND:

High-sensitivity C-reactive protein predicts cardiovascular events in a wide range of clinical contexts. However, the role of high-sensitivity C-reactive protein as a predictive marker for perioperative acute myocardial infarction during noncardiac surgery is not yet clear. The present study investigated high-sensitivity C-reactive protein levels as predictors of acute myocardial infarction risk in patients undergoing high-risk noncardiac surgery.

METHODS:

This concurrent cohort study included patients aged ≥50 years referred for high-risk noncardiac surgery according to American Heart Association/ACC 2002 criteria. Patients with infections were excluded. Electrocardiograms were performed, and biomarkers (Troponin I or T) and/or total creatine phosphokinase and the MB fraction (CPK-T/MB) were evaluated on the first and fourth days after surgery. Patients were followed until discharge. Baseline high-sensitivity C-reactive protein levels were compared between patients with and without acute myocardial infarction.

RESULTS:

A total of 101 patients undergoing noncardiac surgery, including 33 vascular procedures (17 aortic and 16 peripheral artery revascularizations), were studied. Sixty of the patients were men, and their mean age was 66 years. Baseline levels of high-sensitivity C-reactive protein were higher in the group with perioperative acute myocardial infarction than in the group with non-acute myocardial infarction patients (mean 48.02 vs. 4.50, p = 0.005). All five acute myocardial infarction cases occurred in vascular surgery patients with high CRP levels.

CONCLUSIONS:

Patients undergoing high-risk noncardiac surgery, especially vascular surgery, and presenting elevated baseline high-sensitivity C-reactive protein levels are at increased risk for perioperative acute myocardial infarction.     

CTNNB1, AXIN1 and APC expression analysis of different medulloblastoma variants

OBJECTIVES:

We investigated four components of the Wnt signaling pathway in medulloblastomas. Medulloblastoma is the most common type of malignant pediatric brain tumor, and the Wnt signaling pathway has been shown to be activated in this type of tumor.

METHODS:

Sixty-one medulloblastoma cases were analyzed for β-catenin gene (CTNNB1) mutations, β-catenin protein expression via immunostaining and Wnt signaling pathway-related gene expression. All data were correlated with histological subtypes and patient clinical information.

RESULTS:

CTNNB1 sequencing analysis revealed that 11 out of 61 medulloblastomas harbored missense mutations in residues 32, 33, 34 and 37, which are located in exon 3. These mutations alter the glycogen synthase kinase-3β phosphorylation sites, which participate in β-catenin degradation. No significant differences were observed between mutation status and histological medulloblastoma type, patient age and overall or progression-free survival times. Nuclear β-catenin accumulation, which was observed in 27.9% of the cases, was not associated with the histological type, CTNNB1 mutation status or tumor cell dissemination. The relative expression levels of genes that code for proteins involved in the Wnt signaling pathway (CTNNB1, APC, AXIN1 and WNT1) were also analyzed, but no significant correlations were found. In addition, large-cell variant medulloblastomas presented lower relative CTNNB1 expression as compared to the other tumor variants.

CONCLUSIONS:

A small subset of medulloblastomas carry CTNNB1 mutations with consequent nuclear accumulation of β-catenin. The Wnt signaling pathway plays a role in classic, desmoplastic and extensive nodularity medulloblastoma variants but not in large-cell medulloblastomas.     

High admission levels of γ-glutamyltransferase predict poor myocardial perfusion after primary percutaneous intervention

OBJECTIVE:

This retrospective study aimed to investigate the relationship between admission levels of serum γ-glutamyltransferase and poor myocardial perfusion after primary percutaneous coronary intervention in patients with acute myocardial infarction.

INTRODUCTION:

Reperfusion injury caused by free radical release and increased oxidative stress is responsible for the pathophysiology of the no-reflow phenomenon in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention. Serum γ-glutamyltransferase is an established marker of increased oxidative stress.

METHODS:

The study population consisted of 80 patients (64 men and 16 women, mean age = 67.5±6.6 years) with thrombolysis in myocardial infarction 0/1 flow pre-procedurally. The patients were divided into two groups according to thrombolysis in myocardial perfusion grades that were assessed immediately following primary percutaneous coronary intervention. The two groups (group 1 and group 2) each consisted of 40 patients with thrombolysis in myocardial perfusion grades 0-1 and thrombolysis in myocardial perfusion grades 2-3, respectively.

RESULTS:

Admission pain to balloon time, γ-glutamyltransferase and creatine kinase-MB isoenzyme levels of group 1 patients were significantly higher than those of group 2 patients. Pain to balloon time, γ-glutamyltransferase, peak creatine kinase-MB isoenzyme, low left ventricular ejection fraction and poor pre-procedural thrombolysis in myocardial infarction grade were significantly associated with poor myocardial perfusion by univariate analysis. However, only pain to balloon time and γ-glutamyltransferase levels showed a significant independent association with poor myocardial perfusion by backward logistic regression analysis. Adjusted odds ratios were calculated as 4.92 for pain to balloon time and 1.13 for γ-glutamyltransferase.

CONCLUSION:

High admission γ-glutamyltransferase levels are associated with poor myocardial perfusion in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention, particularly in patients with prolonged pain to balloon time.     

What is the influence of hormone therapy on homocysteine and crp levels in postmenopausal women?

OBJECTIVE:

To evaluate the influence of estrogen therapy and estrogen-progestin therapy on homocysteine and C-reactive protein levels in postmenopausal women.

METHODS:

In total, 99 postmenopausal women were included in this double-blind, randomized clinical trial and divided into three groups: Group A used estrogen therapy alone (2.0 mg of 17β-estradiol), Group B received estrogen-progestin therapy (2.0 mg of 17 β-estradiol +1.0 mg of norethisterone acetate) and Group C received a placebo (control). The length of treatment was six months. Serum measurements of homocysteine and C-reactive protein were carried out prior to the onset of treatment and following six months of therapy.

RESULTS:

After six months of treatment, there was a 20.7% reduction in homocysteine levels and a 100.5% increase in C-reactive protein levels in the group of women who used estrogen therapy. With respect to the estrogen-progestin group, there was a 12.2% decrease in homocysteine levels and a 93.5% increase in C-reactive protein levels.

CONCLUSION:

Our data suggested that hormone therapy (unopposed estrogen or estrogen associated with progestin) may have a positive influence on decreasing cardiovascular risk due to a significant reduction in homocysteine levels.     

Tgf-β1 expression as a biomarker of poor prognosis in prostate cancer

OBJECTIVE:

To evaluate the correlation between transforming growth factor beta (TGF-β1) expression and prognosis in prostate cancer.

PATIENTS AND METHODS:

TGF-β1 expression levels were analyzed using the quantitative real-time polymerase chain reaction to amplify RNA that had been isolated from fresh-frozen malignant and benign tissue specimens collected from 89 patients who had clinically localized prostate cancer and had been treated with radical prostatectomy. The control group consisted of 11 patients with benign prostate hyperplasia. The expression levels of TGF-β1 were compared between the groups in terms of Gleason scores, pathological staging, and prostate-specific antigen serum levels.

RESULTS:

In the majority of the tumor samples, TGF-β1 was underexpressed 67.0% of PCa patients. The same expression pattern was identified in benign tissues of patients with prostate cancer. Although most cases exhibited underexpression of TGF-β1, a higher expression level was found in patients with Gleason scores ≥7 when compared to patients with Gleason scores <7 (p = 0.002). Among the 26 cases of TGF-β1 overexpression, 92.3% had poor prognostic features.

CONCLUSIONS:

TGF-β1 was underexpressed in prostate cancers; however, higher expression was observed in tumors with higher Gleason scores, which suggests that TGF-β1 expression may be a useful prognostic marker for prostate cancer. Further studies of clinical specimens are needed to clarify the role of TGF-β1 in prostate carcinogenesis.     

Short-Term Treatment with Metformin Improves the Cardiovascular Risk Profile in First-Degree Relatives of Subjects with Type 2 Diabetes Mellitus who have a Metabolic Syndrome and Normal Glucose Tolerance without Changes in C-Reactive Protein or Fibrinogen

OBJECTIVE:

To study if metformin, when administered to first-degree relatives of type 2 diabetes mellitus subjects who have metabolic syndrome and normal glucose tolerance, could improve the cardiovascular risk profile and reduce the levels of both C-reactive protein and fibrinogen.

INTRODUCTION:

Metabolic syndrome is associated with higher cardiovascular morbidity and mortality. Metformin has vasculo-protective effects even in normoglycemic subjects, and C-reactive protein and fibrinogen are considered markers of endothelial injury and inflammation.

METHODS:

Thirty-one non-diabetic first-degree relatives of type 2 diabetes mellitus subjects with metabolic syndrome were randomized (1:1) and double-blinded for placement in the placebo and metformin groups (850mg bid/±90days); 16 subjects were administered metformin (mean age 40.0 [33.5–50] years; 13 females) and 15 subjects were in the placebo group (mean age 37.0 [32–42] years; 9 females). Blood samples were collected at baseline and at the end of treatment for biochemical analyses, including an assessment of C-reactive protein and fibrinogen levels.

RESULTS:

Metformin improved the lipid profile and decreased fasting plasma glucose, systolic blood pressure, weight and body mass index without changing body composition. For those in the placebo we identified no changes in fibrinogen (282.2 [220.4–323.7] mg/L vs. 286.7 [249.6–295.1] mg/L; NS) or in C-reactive protein levels (0.68 [0.3–1.2] vs. 0.64 [0.3–1.0] mg/L; NS). The same was also observed for the levels of fibrinogen (303.9 [217.6–347.6] mg/L vs. 290.9 [251.5–301.9] mg/L; NS) and C-reactive proteins (0.78 [0.3–1.1] vs. 0.80 [0.4–0.9] mg/L; NS) in the metformin group.

CONCLUSIONS:

Metformin treatment in first-degree relatives of type 2 diabetes mellitus sufferers who have metabolic syndrome and normal glucose tolerance improved the cardiovascular risk profile without changing the levels of C-reactive protein and fibrinogen.     

Residual C-peptide in patients with Type 1 diabetes and multiethnic backgrounds

OBJECTIVE:

To evaluate serum C-peptide in 88 patients from a multiethnic population with Type-1 diabetes and variable disease durations.

METHOD:

Eighty-eight patients with a mean disease duration of 8.1±7.6 years were included and underwent C-peptide measurement before and after glucagon stimulation. Chi-squared and Mann Whitney U-tests were used to compare the variables between groups (all two-tailed, α  = 0.05). Spearmańs correlation coefficient was used to test the association between the continuous variables. Logistic regression was used for the multivariate analysis. Twenty-eight (31.8%) individuals had significantly detectable C-peptide levels after stimuli, particularly those with a shorter disease duration (p<0.001).

RESULTS:

Patients with detectable C-peptide levels required lower insulin doses (p<0.009) and had similar HbA1C results (p = 0.182) and fewer chronic complications (p = 0.029).

CONCLUSION:

C-peptide detection was common in Type-1 diabetics, particularly shortly after being diagnosed. This result may have clinical implications.     

Statin therapy blunts inflammatory activation and improves prognosis and left ventricular performance assessed by Tissue Doppler Imaging in subjects with chronic ischemic heart failure: results from the Daunia Heart Failure Registry

BACKGROUND:

A limited number of studies have used Tissue Doppler Imaging (TDI) to evaluate the effect of statin therapy on left ventricular dysfunction in patients with chronic heart failure. In this work, we aimed to determine whether statin administration influenced prognosis, inflammatory activation and myocardial performance evaluated by Tissue Doppler Imaging in subjects enrolled in the Daunia Heart Failure Registry, a local registry of patients with chronic heart failure.

METHODS:

This study retrospectively analyzed 353 consecutive outpatients with chronic heart failure (mean follow-up 384 days), based on whether statin therapy was used. In all patients, several Tissue Doppler Imaging parameters were measured; circulating levels of interleukin (IL)-6, IL-10 and C-reactive protein were also assayed.

RESULTS:

Statin administration in 128 subjects with ischemic heart disease was associated with a lower incidence of adverse events (rehospitalization for HF 15% vs. 46%, p<0.001; ventricular arrhythmias 5% vs. 21%, p<0.01; cardiac death 1% vs. 8%, p<0.05), lower circulating levels of IL-6 (p<0.05) and IL-10 (p<0.01), lower rates of chronic heart failure (p<0.001) and better Tissue Doppler Imaging performance (E/E'' ratio 12.82±5.42 vs. 19.85±9.14, p<0.001; ET: 260.62±44.16 vs. 227.11±37.58 ms, p<0.05; TP: 176.79±49.93 vs. 136.7±37.78 ms, p<0.05 and St: 352.35±43.17 vs. 310.67±66.46±37.78 ms, p<0.05).

CONCLUSIONS:

Chronic ischemic heart failure outpatients undergoing statin treatment had fewer readmissions for adverse events, blunted inflammatory activation and improved left ventricular performance assessed by Tissue Doppler Imaging.