The effect of Helicobacter pylori eradication on proteinuria in patients with primary glomerulonephritis

Introduction

Glomerulonephritis is still the primary cause among the diseases causing end stage renal disease. Helicobacter pylori (HP), also having a local proinflammatory effect on gastric mucosa, can trigger a local and systemic inflammatory response, and consequently have a role in the development of extragastrointestinal defects.

Material and methods

The study was composed of patients diagnosed with primary glomerulonephritis who had dyspeptic complaints throughout the diagnosis. Patients who received endoscopic biopsy upon the determination of pathologic findings in their upper gastrointestinal endoscopy were HP positive in their biopsy material. A triple eradication therapy was initiated for HP.

Results

The study included 14 female and 19 male patients, 33 in total, whose biopsy material was determined to be HP positive. Before the eradication for HP, we found serum albumin to be 34.0 (19.0–51.0) g/l, serum total protein 58.6 ±12.9 g/l, serum creatinine 0.9 (0.5–1.2) and proteinuria 3069 (652–12392) mg/day in 24-hour urine. After the eradication, however, serum albumin was found to be 40 (20–52) g/l, serum total protein 62.3 ±11.1 g/l, serum creatinine 1.02 (0.6–1.29) mg/dl and proteinuria was 2850 (172–15181) mg/day in 24-hour urine. A comparison of the results showed that a statistically significant difference is established between the serum albumin, total protein and creatinine values (p = 0.001, p = 0.001 and p = 0.021, respectively), but not between proteinuria values in 24-hour urine (p = 0.990).

Conclusions

Patients with primary glomerulonephritis, HP eradication treatment has an effect on serum albumin levels.     

Clinical efficacy and safety of colistin treatment in patients with pulmonary infection caused by Pseudomonas aeruginosa or Acinetobacter baumannii: a meta-analysis

Introduction

The aim of this study was to evaluate the efficacy and safety of colistin treatment in patients with pulmonary infection caused by Pseudomonas aeruginosa or Acinetobacter baumannii.

Material and methods

The relevant studies were identified through a search of public databases including PubMed, MEDLINE and EMBASE up to December 2012. A meta-analysis was conducted to compare the clinical response, mortality and renal damage of colistin (colistin group) versus other effective antibiotics (control group). The odds ratio (OR) was chosen as the effect size.

Results

A total of 9 studies were eventually identified. The result of the meta-analysis showed that the pooled OR of clinical response was 1.24 (95% CI = 0.68–2.27, p > 0.05) for patients in the colistin group versus the control group, indicating no significant difference in efficacy between colistin and control groups. Similar results were obtained by the further subgroup meta-analyses by sample size, research year, ethnicity and study method. Treatment with colistin versus other agents did not affect hospital mortality (OR = 1.05, 95% CI = 0.58–1.89, p > 0.05) or renal damage (OR = 1.25, 95% CI = 0.78–2.00, p > 0.05). The combined estimate of our analysis was strong across multiple sensitivity analyses and without significant publication bias.

Conclusions

Our results suggest that colistin may be as efficacious and safe as standard antibiotics for the treatment of pulmonary infection.     

Renal vascular response to angiotensin II inhibition in intensive antihypertensive treatment of essential hypertension

Introduction

High blood pressure (BP) leads to target organ damage. It is suggested that regression of early organ lesions is possible on condition of BP normalization. The study objective was to assess whether permanent reduction of BP to the recommended values modifies renal vascular response to acute angiotensin II inhibition in the Doppler captopril test (DCT) in patients with essential hypertension (EH).

Material and methods

Twenty-nine persons (58 kidneys) were found eligible for the study: 18 patients with EH and 11 healthy volunteers constituting the control group. Glomerular filtration rate estimation (eGFR), 24-h ambulatory BP monitoring (ABPM) and DCT with evaluation of renal resistive index change (ΔRI) were performed before and after a 6-month period of intensive antihypertensive therapy (IAT). Additional ABPM was performed at the end of IAT.

Results

The mean IAT period was 8.5 ±2.4 months. The mean 24-h values of systolic and diastolic BP in the EH group were significantly lower in the IAT period than at the beginning and at the end of the study. Significantly lower systolic and diastolic BP (p < 0.05) and improvement of renal function (eGFR 121 ±38 vs. 139 ±40 ml/min, p < 0.001) were found after IAT as compared to initial values. Before IAT, ΔRI was significantly lower in the EH group as compared to the controls, but no such differences were found after IAT.

Conclusions

In EH patients, intensive BP lowering to the recommended values was associated with improvement of renal function and normalisation of renal vascular response to acute angiotensin II inhibition.     

Role of cytological characteristics of benign thyroid nodules on effectiveness of their treatment with levothyroxine

Introduction

Levothyroxine (LT4) therapy has been used for the treatment of euthyroid nodular goiter, but there are controversial results about its usefulness. We aimed to evaluate the possible role of benign nodules’ cytological characteristics in response to LT4 therapy.

Material and methods

In total, 93 patients with 128 nodules were included in the study; 74 of the nodules were treated with LT4 (group 1), and 54 of them had no medication (group 2). The subgroups consisted of adenomatous nodules, colloid nodules and cystic nodules.

Results

In group 1, mean thyroid volume and mean nodule volume were reduced significantly (p = 0.002 and p = 0.022, respectively) with low-normal level thyrotropin (TSH) suppression (between 0.3 mIU/ml and 1.0 mIU/ml), while there were no significant changes in group 2. When we evaluated changes of the initial and last nodule volumes in cytological subgroups, only colloid nodules in group 1 had significant reduction (p = 0.040) and the others had no significant changes. By omitting the colloid nodules, when the other nodules were revaluated, there were no significant changes in either group.

Conclusions

On the basis of these results, obtained from a large sample of Anatolian patients, it is possible that LT4 therapy leads to significant reductions of both thyroid volume and nodule size in colloid nodules, but not in other kinds of benign nodules.     

The influence of steroid receptor status on the cardiotoxicity risk in HER2-positive breast cancer patients receiving trastuzumab

Introduction

Expression of steroid receptors and HER2 overexpression in breast cancer cells are predictive and prognostic factors. Overexpression of HER2 allows the use of immunotherapy, in which the most serious side effect is cardiotoxicity. The aim of this study was to evaluate the influence of steroid receptor status on cardiotoxicity risk in HER2 breast cancer patients receiving trastuzumab both in adjuvant treatment and in the case of disease dissemination. This study also assessed well-known cardiac risk factors.

Material and methods

The study was conducted on 166 patients who received immunotherapy in the Clinical and Experimental Oncology Department, between the years 2006 and 2012.

Results

A predisposition to cardiac side effects (13% vs. 5%) in patients with negative steroid receptor status was observed (p = 0.08). The decrease of left ventricular ejection fraction (LVEF) (12% vs. 0) and cardiac adverse side effects (2% vs. 0) were detected only in ER-/PR- patients but without statistical significance. Discontinuation of therapy because of cardiotoxicity was associated with negative receptor status (33% vs. 7%) (p = 0.019). Irrespective of steroid receptor status, older age of patients (p = 0.009) and previous radiotherapy to the left side of the chest (p = 0.02) were associated with the occurrence of cardiotoxicity and decrease of LVEF. In patients who received previous anthracycline-based chemotherapy, acute cardiac side effects were observed significantly more often (p = 0.01).

Conclusions

There was no influence of steroid receptor status on the cardiac side effects. Breast cancer type containing Erb-B2 overexpression was associated with predisposition to cardiotoxicity. The results require confirmation in a larger group of patients.     

Bone mineral density,bone turnover markers,lean mass,and fat mass in Egyptian children with congenital adrenal hyperplasia

Introduction

Aim of this paper is to assess bone mineral density (BMD) and body composition, by dual energy X-ray absorptiometry (DXA), and various markers of bone growth, in a group of children with congenital adrenal hyperplasia (CAH) on long-term glucocorticoid therapy.

Material and methods

A case-control study included thirty patients with CAH with different states of metabolic control. Their mean age was 7.5 ±4.2 years. All patients are subjected to BMD using DXA at the neck of the femur and lumbar spine. A blood sample was taken for assessment of osteocalcin, osteoprotegerin, and procollagen type 1, as markers of bone formation, as well as RANKL and urinary deoxypyridinoline (DPD), as markers of bone resorption.

Results

We found no difference in BMD in patients and control subjects; however, patients showed significantly lower serum osteocalcin (p = 0.008) and osteoprotegerin (p = 0.0001) and significantly higher serum RANKL levels (p = 0.0001). Our results show that patients had significantly lower lean body mass (p = 0.005) and fat/lean ratio (p = 0.008) compared to matched controls. The duration of treatment showed a significant negative correlation with procollagen type 1 (r = –0.49, p = 0.02) and lean mass % (r = –0.43, p = 0.04); however, it showed a significant positive correlation with total fat mass % (r = 0.6, p = 0.0006), and fat/lean ratio (r = 0.43, p = 0.04). Dose of steroid had a significant positive correlation with BMI SDS (r = 0.4, p = 0.02).

Conclusions

Bone mineral density is normal but bone turnover is low in patients with CAH. There is an increase in fat/lean mass in patients with CAH.     

Stepwise Treatment Using Corticosteroids Alone and in Combination with Cyclosporine in Korean Patients with Idiopathic Membranous Nephropathy

Purpose

We undertook an observational study to investigate the effects of immunosuppressive treatment on proteinuria and renal function in 179 Korean idiopathic membranous nephropathy patients with nephrotic syndrome.

Materials and Methods

The primary outcome was regarded as the first appearance of remission and the secondary outcomes as a decline in estimated glomerular filtration rate (eGFR) >50% or initiation of dialysis, and all-cause mortality. Seventy-two (40.2%) and 50 (27.9%) patients were treated with corticosteroids alone (C) and corticosteroids plus cyclosporine (C+C), respectively, whereas 57 (31.8%) did not receive immunosuppressants (NTx). Cyclosporine was added if there was no reduction in proteinuria of >50% from baseline by corticosteroids alone within 3 months.

Results

There were no differences in baseline renal function and the amount of proteinuria among the three groups. Overall, complete remission (CR) was achieved in 88 (72.1%) patients by immunosuppressants. In a multivariate analysis adjusted for covariates associated with adverse renal outcome, the probability of reaching CR was significantly higher in the C [hazard ratio (HR), 4.09; p<0.001] and C+C groups (HR, 2.57; p=0.003) than in the NTx group. Kaplan-Meier analysis revealed that 5-year CR rates of C, C+C, and NTx groups were 88.5%, 86.2%, and 56.7% (p<0.001). Ten-year event-free rates for the secondary endpoints in these three groups were 91.7%, 79.9%, and 57.2% (p=0.01).

Conclusion

Immunosuppressive treatment was effective in inducing remission and preserving renal function in these patients. Therefore, stepwise treatment using corticosteroids alone and in combination with cyclosporine is warranted in these patients.     

Multifactorial analysis of risk factors for reduced bone mineral density among postmenopausal women

Introduction

The study aimed to determine the risk factors for reduced bone mineral density (BMD) among postmenopausal women.

Material and methods

Two hundred and fifty-three postmenopausal women were included to the study. The study group consisted of 85 women with osteoporosis (mean age: 59.9 years) and 168 with osteopenia (mean age: 57.8 years). Patients were assigned to groups according to their BMD measured in the lumbar spine, hip and femoral neck by dual X-ray absorptiometry. Bone formation was assessed by measuring serum osteocalcin and bone resorption by measuring serum C-terminal type I α-collagen chain telopeptide.

Results

Multiple regression analysis for lumbar spine showed association of age (p = 0.001), parental history of fracture (p = 0.05), use of hormone replacement therapy (p = 0.034), bisphosphonates therapy (p < 0.001), calcium and vitamin D supplements therapy (p = 0.001), oestradiol level (p = 0.007) and body mass index (p < 0.001). Multiple regression analysis for femoral neck and hip total showed association of age (p = 0.001), parental history of fracture (p = 0.049), use of bisphosphonates (p < 0.03)) use of calcium and vitamin D supplements (p = 0.039), oestradiol level (p = 0.047). All the variables together explain 40.4% of variance in BMD for the lumbar spine and 25.6% of variance in BMD for femoral neck and hip total.

Conclusions

The present study demonstrated correlations between the variables and BMD, which are known and widely described in the literature. Osteoporosis and osteopenia in Polish subjects appear to be associated with several known risk factors that are well described in the literature.     

Ovarian reserve markers in unexplained infertility patients treated with clomiphene citrate during intrauterine insemination

Introduction

The aim of this retrospective case control study was to identify predictors of ovarian response and pregnancy outcomes in intrauterine insemination (IUI).

Material and methods

One hundred women undergoing IUI cycles with clomiphene citrate were enrolled. The number of antral follicles and the total ovarian volume by ultrasound, and the basal levels of follicle-stimulating hormone (FSH), estradiol, and inhibin B on cycle day 3 were measured in groups that were divided according to ovarian response. The tests were also evaluated according to ovarian response and pregnancy outcomes. All analyses were performed using the Statistical Package for the Social Sciences, version 15.0 (SPSS, Chicago, IL, USA).

Results

The antral follicle count (AFC) was the best single predictor for ovarian response and pregnancy outcomes. The sensitivity and specificity for prediction of ovarian response were 81% and 78% for AFC at an optimum cutoff value of ≤ 13.1. Age was negatively correlated with ovarian volume (r = –0.280, p = 0.021) and AFC (r = –0.358, p = 0.003). Increasing FSH was associated with a reduction in AFC (r = –0.273, p = 0.025). The AFC was significantly correlated with ovarian volume (r = 0.660, p < 0.0001) and FSH (r = –0.273, p = 0.03).

Conclusions

Our data demonstrate that the AFC provides better prognostic information on the occurrence of ovarian response during clomiphene citrate stimulation for IUI.     

Strain of experimental animals and modulation of nitric oxide pathway: their influence on development of renal failure in an experimental model of hepatorenal syndrome

Introduction

Pathomechanism of HRS is still poorly understood. The aim of our study was: (1) to test whether different strains of rats could develop typical HRS, and (2) to estimate the influence of activation and inhibition of nitric oxide for development of renal failure in course of HRS.

Material and methods

First, we used 16 of Wistar and 16 of Sprague-Dawley rats in galactosamine model of HRS. Next, we used 48 of SDR rats, which received saline, N-nitro-L-arginine or L-arginine before and after liver damage. Twenty four hours urine and blood samples were collected 48 h after saline or Ga1N injection. Biochemical parameters were determined in serum or urine and then creatinine clearance and osmolality clearance were calculated. Liver and kidney tissues were collected for histopathological examination.

Results

Liver failure developed in all tested groups with significant increase of bilirubin (p < 0.001), ALT (p < 0.001) and ammonia (p < 0.001). Nevertheless we did not achieve any evidence of renal failure in Wistar, but we found typical renal failure in Sprague-Dawley group with significant decrease in creatinine clearance (p < 0.0012) and increase in concentration of creatinine and urea (p < 0.001) and (p < 0.001) respectively. Inhibition of NOS prevented development of renal failure with significant improvement of GFR both before (p < 0.0017) and after (p < 0.003) Ga1N injection. Injection of L-arginine after Ga1N injection did not caused significant improvement of GFR.

Conclusions

Our study showed, that genetic factors might be responsible for development of renal failure in course of HRS and nitric oxide play important role in acute model of this syndrome.     

Ondansetron-droperidol combination vs. ondansetron or droperidol monotherapy in the prevention of postoperative nausea and vomiting

Introduction

Laparoscopic cholecystectomy is associated with a high incidence of postoperative nausea and vomiting. In this study we investigated comparatively the efficacy of combination therapy with ondansetron plus droperidol versus monotherapy with each agent alone in preventing postoperative nausea and vomiting following elective laparoscopic cholecystectomy.

Material and methods

One hundred twenty-seven patients who underwent elective laparoscopic cholecystectomy under general anesthesia were included in the study, and assigned to one of the following three groups according to the antiemetic drug given intravenously at the end of the surgery: droperidol 1.25 mg in group D, ondansetron 4 mg in group O, and a combination of droperidol and ondansetron at the doses mentioned above in group D + O. Incidence of postoperative nausea and vomiting, and doses of given rescue antiemetics were recorded during the first postoperative day. The total drug cost per patient spent for postoperative nausea and vomiting management (including prophylactic antiemetics plus rescue postoperative antiemetics) was calculated.

Results

Combination therapy significantly reduced postoperative nausea and vomiting at 30 min, 3 h and 6 h after surgery compared with group D (p < 0.01 for all time points) and O (p < 0.01 at 30 min, p < 0.05 at 3 h) and required less rescue antiemetic treatment (p < 0.01). Total antiemetic cost analyses revealed no significant differences among the three groups (p > 0.05).

Conclusions

Pretreatment with ondansetron plus droperidol is more effective than monotherapy in preventing postoperative nausea and vomiting following laparoscopic cholecystectomy, without increasing the cost comparatively.     

Clinicopathologic characteristics and prognostic factors for HER2-positive patients with metastatic breast cancer in southern China

Introduction

The aim of the study was to analyze clinicopathologic characteristics and survival and to identify prognostic factors for Chinese patients with HER2-positive metastatic breast cancer.

Material and methods

A total of 243 patients with HER2-positive metastatic breast cancer, treated during the period 2002 to 2009, were followed up from initial disease diagnosis to death or date of last follow-up (December 2011). Cumulative survival curves were created using Kaplan-Meier analysis with the log-rank test. Prognostic factors were analyzed by univariate and multivariate Cox proportional hazards regression analysis.

Results

During follow-up, 205 patients died, with a median OS of 27 months (95% CI: 23.5, 30.5 months), and the 1-, 3-, and 5-year survival rates were 84.4%, 38.6%, and 18.1%, respectively. The median OS of HR+ patients was significantly higher than that of HR– patients (p < 0.001). Surgery (hazard ratio = 0.60, p = 0.002), endocrine therapy (hazard ratio = 0.53, p < 0.01), and anti-HER2 therapy (hazard ratio = 0.63, p = 0.003) were favorable independent prognostic factors for patients with HER2-positive metastatic breast cancer.

Conclusions

These results indicated that surgical intervention, endocrine therapy, and anti-HER2 therapy were good for these HER2 positive patients with metastatic breast cancer, but ECOG performance status < 1 and metastasis to brain were unfavorable independent prognostic factors. HR status was not an independent prognostic factor.     

Sleep changes following statin therapy: a systematic review and meta-analysis of randomized placebo-controlled polysomnographic trials

Introduction

Statin use might be associated with an increased risk of sleep disturbances including insomnia, but the evidence regarding sleep changes following statin therapy has not been conclusive. Therefore we assessed the impact of statin therapy on sleep changes through a systematic review and meta-analysis of available randomized controlled trials (RCTs).

Material and methods

We searched MEDLINE and SCOPUS up to October 1, 2014 to identify placebo-controlled RCTs investigating the effect of statin therapy on sleep changes. A meta-analysis was performed using either a fixed-effects or a random-effect model according to the I2 statistic. Effect size was expressed as weighted mean difference (WMD) and 95% confidence interval (CI).

Results

Overall, the impact of statin therapy on polysomnography (PSG) indices of sleep was reported in 5 trials comprising 9 treatment arms. Overall, statin therapy had no significant effect on total sleep duration (WMD: –7.75 min, 95% CI: –18.98, 3.48, p = 0.176), sleep efficiency (WMD: 0.09%, 95% CI: –2.27, 2.46, p = 0.940), entries to stage I (WMD: 0.36, 95% CI: –0.91, 1.63, p = 0.580), or latency to stage I (WMD: –1.92 min, 95% CI: –4.74, 0.89, p = 0.181). In contrast, statin therapy significantly reduced wake time (WMD: –4.43 min, 95% CI: –7.77, –0.88, p = 0.014) and number of awakenings (WMD: –0.40, 95% CI: –0.46, –0.33, p < 0.001). Meta-regression did not suggest any correlation between changes in wake time and awakening episodes with duration of treatment and LDL-lowering effect of statins.

Conclusions

The results indicated that statins have no significant adverse effect on sleep duration and efficiency, entry to stage I, or latency to stage I sleep, but significantly reduce wake time and number of awakenings.     

The roles of connective tissue growth factor in the development of anastomotic esophageal strictures

Introduction

The aim of this study was to investigate the roles of connective tissue growth factor (CTGF) in the development of anastomotic strictures after surgical repair of the esophagus.

Material and methods

Tissues collected from the patients were divided into three groups based on the results of endoscopy and clinical grading. Patients without dysphagia after esophagectomy were used as the control population. The protein levels of CTGF, TGF-β1, Smad2, and Smad4 were determined by immunohistochemistry (IHC) and western blot analyses, while the mRNA levels of the two growth factors were evaluated by real-time polymerase chain reaction.

Results

Compared with the control group, significantly increased (p < 0.01) levels of CTGF and TGF-β1 protein were observed in the anastomotic stenosis (AS) group, and levels of the two proteins detected by the IHC and western blot analyses were also significantly increased with the increasing severity of stenosis (p < 0.05). The mRNA levels of CTGF and TGF-β1 in the tissues collected from the patients with stenosis were significantly up-regulated (p < 0.05) as compared with those from the control group. In addition, the levels of Smad2 and Smad4 protein were also significantly increased (p < 0.05) with the increasing severity of stenosis, and the protein levels were positively correlated with the levels of CTGF (r = 0.59, p < 0.05) and TGF-β1 (r = 0.63, p < 0.05).

Conclusions

Inhibition of CTGF protein or mRNA expression may be a distinctive and effective therapy for the treatment of postoperative anastomotic strictures.     

The anti-tumor effect of a polypeptide extracted from Tegillarca granosa Linnaeus on renal metastatic tumor OS-RC-2 cells

Introduction

Renal cell carcinoma is a type of malignant tumor often diagnosed in the urinary system. The aim of this study is to evaluate the anti-tumor effects and mechanisms of a polypeptide, Haishengsu (TG-1), with different concentrations (125, 250, 500 mg/kg) on renal metastatic tumor OS-RC-2 cells.

Material and methods

We first established the renal metastatic tumor model. After being administered with TG-1, the weight of tumors was measured and the microstructural changes of renal carcinoma OS-RC-2 cells were compared using transmission electron microscopy before and after the therapy. The Ki67 expression in renal carcinoma OS-RC-2 cells was analyzed by RT-PCR and downstream signal molecule caspase-3 was measured by Western blot assay.

Results

After treatment with different doses of TG-1, the tumor weights in the positive control group and experimental groups were smaller than those in the untreated control group, suggesting that TG-1 could effectively inhibit tumor growth in mice. The transmission electron microscopy and flow cytometry results indicated that TG-1 induces tumor cell apoptosis (p < 0.05). The tumor cells exhibited polymorphism changes and chromatin edge clustering. TG-1 also inhibited Ki67 expression and promoted caspase-3 expression in the tumor significantly (p < 0.05).

Conclusions

TG-1 inhibits the growth of the tumor and induces apoptosis of the tumor cells by inducing caspase-3 expression. The results provide a basis for clinical application of TG-1 in the future.     

Distinctive biochemical changes in pulmonary tuberculosis and pneumonia

Introduction

We aimed to investigate the relationship between radiological extent and serum biochemical changes and body mass index (BMI) in patients with pulmonary tuberculosis (PTB) and pneumonia and to determine the usefulness of C-reactive protein (CRP) in clinical discriminative diagnosis.

Material and methods

One hundred fifteen patients with tuberculosis (group 1), 70 patients with pneumonia (group 2) and 30 healthy controls (group 3) were included in this case-control study.

Results

Total cholesterol (TC, p < 0.001 in group 1; p = 0.011 in group 2), high-density lipoprotein (HDL, p < 0.001), albumin (ALB, p < 0.001) and BMI (p < 0.001) values were significantly lower group 1 and group 2 than group 3. Erythrocyte sedimentation rate (ESR), leucocyte (LEU) and CRP were higher in group 2 than group 1 and group 3 (p < 0.001). As important point; triglyceride (TG) and BMI were significantly lower in group 1 than group 2 (p < 0.001). In group 1; BMI, HDL, TG, total protein (TP) and albumin were found to decrease, while CRP and ESR increased as the radiological stage increased (p < 0.05). But no significant difference was found in levels of TC and LDL (p > 0.05). In group 2; BMI, TC, HDL, LDL, TP and ALB were observed to decrease, while LEU, CRP and ESR increased as the radiological stage increased (p < 0.05). But no significant difference was found in levels of TG (p > 0.05). The best serum CRP cut-off value in differential diagnosis of tuberculosis and pneumonia was defined as 9.4.

Conclusions

The acute phase response occurring in tuberculosis and pneumonia determines the severity of the disease, leads to a decrease of serum levels of lipoproteins and BMI, and is correlated with the radiological extent. The CRP and ESR were found to be useful in differential diagnosis of tuberculosis and pneumonia.     

The influence of statin therapy on platelet activity markers in hyperlipidemic patients after ischemic stroke

Introduction

Low-density lipoprotein cholesterol (LDL-C) has been reported to increase platelet activation. Reducing the level of LDL-C with statins induces important pleiotropic effects such as platelet inhibition. This association between platelet activity and statin therapy may be clinically important in reducing the risk of ischemic stroke. We investigated the effect of simvastatin therapy on platelet activation markers (platelet CD62P, sP-selectin, and platelet-derived microparticles (PDMPs)) in hyperlipidemic patients after ischemic stroke.

Material and methods

The study group consisted of 21 hyperlipidemic patients after ischemic stroke confirmed by CT, and 20 healthy subjects served as controls. We assessed the CD62P expression on resting and thrombin-activated blood platelets. CD62P and PDMPs were analyzed by the use of monoclonal antibodies anti-CD61 and anti-CD62 on a flow cytometer. The level of sP-selectin in serum was measured by the ELISA (enzyme-linked immunosorbent assay) method. All markers were re-analyzed after 6 months of treatment with simvastatin (20 mg/day).

Results

Hyperlipidemic patients presented a significantly higher percentage of CD62+ platelets and higher reactivity to thrombin compared to control subjects. After simvastatin therapy hyperlipidemic patients showed a reduction of the percentage of resting CD62P(+) platelets (p = 0.005) and a reduction of expression and percentage of CD62P(+) platelets after activation by thrombin (median p < 0.05; percentage: p = 0.001). A decrease of sP-selectin levels (p = 0.001) and percentage of PDMPs (p < 0.05) in this group was also observed.

Conclusions

HMG-CoA reductase inhibitor therapy in stroke patients with hyperlipidemia may be useful not only due to the lipid-lowering effect but also because of a significant role in reduction of platelet activation and reactivity.     

Procalcitonin kinetics – prognostic and diagnostic significance in septic patients

Introduction

Severe sepsis and septic shock are advanced clinical conditions representing the patient''s response to infection and having a variable but high mortality rate. Early evaluation of sepsis stage and choice of adequate treatment are key factors for survival. Some study results suggest the necessity of daily procalcitonin (PCT) monitoring because of its prognostic and discriminative value.

Material and methods

An observational and prospective study was conducted to evaluate the prognostic and discriminative value of PCT kinetics in comparison to PCT absolute value measurements. In a group of 50 intensive care unit patients with diagnosis of severe sepsis or septic shock, serum PCT measurements were performed on admission, and on the 2^nd, 3^rd and 5^th day of therapy. The level of PCT was determined with a commercially available test according to the manufacturer''s protocol.

Results

The kinetics of PCT assessed by ΔPCT was statistically significant in the survivors vs. the non-survivors subgroup (ΔPCT_3/1, p = 0.022; ΔPCT_5/1, p = 0.021). ΔPCT has no statistical significance in the severe sepsis and septic shock subgroups for all analyzed days. Only the 5^th day PCT level was significantly higher in the non-survivors vs. survivors group (p = 0.008). The 1^st day PCT level in the severe sepsis vs. septic shock group has a discriminative impact (p = 0.009).

Conclusions

According to the results, single serum PCT measurement, regardless of absolute value, has a discriminative impact but no prognostic significance, during the first 2 days of therapy. The PCT kinetics is of prognostic value from the 3^rd day and is of earlier prognostic significance in comparison to changes in the patient''s clinical condition evaluated by SOFA score kinetics.     

The effect of combining rosuvastatin with sartans of different peroxisome proliferator receptor-γ activating capacity on plasma 8-isoprostane prostaglandin F2a levels

Introduction

Oxidative stress is associated with the development and progression of cardiovascular disease. Plasma 8-isoprostane prostaglandin F_2a (8-iso-PGF_2a) levels are a reliable marker of oxidative stress.

Material and methods

Patients (n = 151) with hypertension, dyslipidemia and impaired fasting glucose were randomly allocated to rosuvastatin (10 mg/day) plus telmisartan 80 mg/day (RT group, n = 52) or irbesartan 300 mg/day (RI group, n = 48) or olmesartan 20 mg/day (RO group, n = 51). After 6 months of treatment, changes in plasma 8-iso-PGF_2a levels were blindly evaluated.

Results

A decrease of 8-iso-PGF_2a levels vs baseline was observed only in the RT group (–8.6%; p = 0.02). A trend for decrease vs. baseline was observed in the RI (–5.7%; p = 0.40) and RO (–3.7%; p = 0.60) groups. Changes of 8-iso-PGF_2a levels between groups were not significantly different (p = 0.70).

Conclusions

The combination of rosuvastatin with sartans of different peroxisome proliferator receptor-γ activating capacity was associated with a decrease in levels of plasma 8-iso-PGF_2a. This decrease reached significance only in the telmisartan group.     

Antithrombotic therapy – predictor of early and long-term bleeding complications after transcatheter aortic valve implantation

Introduction

Dual antiplatelet therapy (DAPT) – aspirin and clopidogrel – is recommended after transcatheter aortic valve implantation (TAVI) without an evidence base. The main aim of the study was to estimate the impact of antithrombotic therapy on early and late bleeding. Moreover, we assessed the impact of patients’ characteristics on early bleeding and the influence of bleeding on prognosis.

Material and methods

Between 2009 and 2011, 83 consecutive TAVI patients, age 81.1 ±7.2 years, were included. Bleeding complications were defined by the Valve Academic Research Consortium (VARC) scale. The median follow-up was 12 ±15.5 months (range: 1 to 23) and included 68 (81.9%) patients.

Results

Early bleeding occurred in 51 (61.4%) patients. Vitamin K antagonists (VKA) pre-TAVI (p = 0.001) and VKA + clopidogrel early post-TAVI (p = 0.04) were the safest therapies; in comparison to the safest one, peri-procedural DAPT (p = 0.002; p = 0.05) or triple anticoagulant therapy (TAT) (p = 0.003, p = 0.05) increased the risk for early bleeding. Predictors for early bleeding were: clopidogrel pre-TAVI (OR: 4.43, 95% CI: 1.02–19.24, p = 0.04), preceding percutaneous coronary intervention (PCI) (10.08, OR: 95% CI: 1.12–90.56, p = 0.04), anemia (OR: 4.00, 95% CI: 1.32–12.15, p = 0.01), age > 85 years (OR: 5.96, 95% CI: 1.47–24.13, p = 0.01), body mass index (BMI) (OR: 0.86, 95% CI: 0.74–0.99, p = 0.04). Late bleeding occurred in 35 patients (51.4%) on combined therapy, and none on VKA or clopidogrel monotherapy (p = 0.04). Bleeding complications did not worsen the survival.

Conclusions

This study seems to suggest that advanced age, BMI, and a history of anemia increased the risk for early bleeding after TAVI. Clopidogrel pre-TAVI should be avoided; therefore, time of preceding PCI should take into account discontinuation of clopidogrel in the pre-TAVI period. Vitamin K antagonists with clopidogrel seems to be the safest therapy in the early post-TAVI period, similarly as VKA/clopidogrel monotherapy in long-term prophylaxis.