Diagnostic accuracy of loop-mediated isothermal amplification in detection of Clostridium difficile in stool samples: a meta-analysis

Introduction

Clostridium difficile infection (CDI) remains a diagnostic challenge for clinicians. More recently, loop-mediated isothermal amplification (LAMP) has become readily available for the diagnosis of CDI, and many studies have investigated the usefulness of LAMP for rapid and accurate diagnosis of CDI. However, the overall diagnostic accuracy of LAMP for CDI remains unclear. In this meta-analysis, our aim was to establish the overall diagnostic accuracy of LAMP in detection of Clostridium difficile (CD) in stool samples.

Material and methods

A search was done in PubMed, MEDLINE, EMBASE and Cochrane Library databases up to February 2014 to identify published studies that evaluated the diagnostic role of LAMP for CD. Methodological quality was assessed according to the quality assessment for studies of diagnostic accuracy (QUADAS) instrument. The sensitivities (SEN), specificities (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) were pooled statistically using random effects models. Statistical analysis was performed by employing Meta-Disc 1.4 software. Summary receiver operating characteristic (SROC) curves were used to summarize overall test performance. Funnel plots were used to test the potential publication bias.

Result

A total of 9 studies met inclusion criteria for the present meta-analysis. The pooled SEN and SPE for diagnosing CD were 0.93 (95% CI: 0.91–0.95) and 0.98 (95% CI: 0.98–0.99), respectively. The PLR was 47.72 (95% CI: 15.10–150.82), NLR was 0.07 (95% CI: 0.04–0.14) and DOR was 745.19 (95% CI: 229.30−2421.72). The area under the ROC was 0.98. Meta-regression indicated that the total number of samples was a source of heterogeneity for LAMP in detection of CD. The funnel plots suggested no publication bias.

Conclusions

The LAMP meets the minimum desirable characteristics of a diagnostic test of SEN, SPE and other measures of accuracy in the diagnosis of CD, and it is suitable as a rapid, effective and reliable stand-alone diagnostic test for diagnosis of CDI, potentially decreasing morbidity and nosocomial spread of CD.     

Association of STAT4 gene rs7574865G > T polymorphism with ulcerative colitis risk: evidence from 1532 cases and 3786 controls

Introduction

Several studies have reported the relationship between the STAT4 rs7574865G > T polymorphism as a susceptibility factor to ulcerative colitis (UC). However, the results have been controversial. Therefore, we conducted this meta-analysis to obtain the most reliable estimate of the association.

Material and methods

PubMed, Embase and Web of Science databases were searched. Crude odds ratios (OR) with 95% confidence intervals (CI) were extracted and pooled to assess the strength of the association between the STAT4 rs7574865G > T polymorphism and risk of UC. A total of five eligible studies including 1532 cases and 3786 controls based on the search criteria were involved in this meta-analysis.

Results

We observed that the STAT4 rs7574865G > T polymorphism was significantly correlated with UC risk when all studies were pooled into the meta-analysis (the allele contrast model: OR = 1.13, 95% CI = 1.02–1.25; the heterozygote codominant model: OR = 1.22, 95% CI = 1.04–1.43; the dominant model: OR = 1.25, 95% CI = 1.07–1.45). In the stratified analysis by ethnicity, significant associations were observed in Spanish for the allele contrast model (OR = 1.20; 95% CI = 1.04–1.39), for the homozygote codominant model (OR = 1.57; 95% CI = 1.07–2.31), for the dominant model (OR = 1.20; 95% CI = 1.01–1.43), and for the recessive model (OR = 1.50; 95% CI = 1.03–2.19).

Conclusions

This meta-analysis suggests that the STAT4 rs7574865G > T polymorphism is a low-penetrant risk factor for UC, especially in Spanish.     

Vitamin D receptor BsmI polymorphism and osteoporosis risk in post-menopausal women

Introduction

Many studies have suggested that the vitamin D receptor polymorphism BsmI might be associated with the risk of osteoporosis development in post-menopausal women. However, the results have been inconsistent. The aim of this meta-analysis was to derive a more precise evaluation of the relationship.

Material and methods

Published literature from PubMed, EMBASE and the CNKI database was searched. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of any association.

Results

Ten case-control studies were included with a total of 1,403 osteoporosis cases and 2,144 healthy controls. In the overall analysis, no significant association was found between BsmI polymorphism and osteoporosis risk (BB vs. bb: OR = 0.76, 95% CI = 0.39–1.48; BB vs. Bb: OR = 0.90, 95% CI = 0.71–1.15; dominant model: OR = 1.20, 95% CI = 0.74–1.93; recessive model: OR = 0.83, 95% CI = 0.53–1.30). In the subgroup analysis by ethnicity, the results showed similar result that BsmI polymorphism m had no association with osteoporosis.

Conclusions

Results from the current meta-analysis suggest that vitamin D receptor BsmI polymorphism may not be a risk factor for osteoporosis in post-menopausal women.     

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.     

Incidental extraspinal findings on magnetic resonance imaging of intervertebral discs

Introduction

We aimed to evaluate pathological extraspinal findings and congenital anomalies/anatomical variations that were incidentally detected on the magnetic resonance imaging (MRI) scans of intervertebral discs, to find the frequencies of these incidental findings, and to emphasise the clinical importance of them.

Material and methods

A retrospective study including 1031 consecutive patients (730 females and 301 males, with a median age of 46 years) was conducted by evaluating a total of 1106 MRI examinations of intervertebral discs. Examinations were performed with a 1.5 T MRI unit. Incidental findings were classified as pathological findings and congenital anomalies/anatomical variations.

Results

The percentages of incidental extraspinal pathological findings and congenital anomalies/anatomical variations were 16.6% (95% confidence interval (CI): 14.4–18.8) and 3.7% (95% CI: 2.6–4.3), respectively. The percentage of incidental extraspinal pathological findings on cervical spinal MRI was 25.7% (95% CI: 20.1–31.7), thyroid nodules being the most common incidental findings. On thoracic spinal MRI (n = 19), inferior pole thyroid nodules were demonstrated as incidental extraspinal pathological findings, with a percentage of 10.5% (95% CI: 9.6–11.5). On lumbar spinal MRI, incidental pathological findings were detected with a percentage of 14.2% (95% CI: 11.9–16.6), while the percentage of congenital anomalies/anatomical variations was 4.8% (95% CI: 3.4–6.3). Eventually, 6.5% (95% CI: 2.6–9.4) of all cases with incidental extraspinal pathological findings underwent surgery.

Conclusions

On MRI examination of intervertebral discs, paying attention to incidentally detected pathological extraspinal findings and congenital anomalies/anatomical variations is very important due to the fact that they can alter the treatment of the patient or affect the patient''s life.     

Clinical features of severe cases of hand,foot and mouth disease with EV71 virus infection in China

Introduction

Hand, foot and mouth disease (HFMD) caused by EV71 infection has become one of the major public health issues in China, which deeply affects children''s health. The prevention and control of EV71 is a challenge currently because there is no safe and effective vaccine or antiviral medications available.

Material and methods

A case control study was conducted in a designated hospital to compare severe and mild cases of patients infected with the EV71 virus. Demographic information along with clinical features of HFMD was collected through a standardized questionnaire. Multi-factorial logistic regression was used to analyze independent associations between potential risk factors and severe HFMD.

Results

There were 120 cases (60 cases and 60 controls) collected. The male-to-female ratio was 1.3: 1 in the case group and 1.7: 1 in the control group. Multi-factorial logistic regression revealed that the main risk factors for severe cases were highest body temperature being ≥ 38.5°C (OR = 9.45, 95% CI: 2.07–43.11, p < 0.05), first visited a village level clinic (OR = 4.72, 95% CI: 1.15–19.45, p < 0.05), etc.

Conclusions

Close surveillance combined with laboratory testing should be in place during the epidemic period of HFMD. Grass root level medical facilities and training of clinical and laboratory staff should be reinforced so that the diagnostic and treatment capacity can be improved.     

Asymmetrical dimethylarginine and severity of erectile dysfunction and their impact on cardiovascular events in patients with acute coronary syndrome

Introduction

Coronary artery disease (CAD) and vascular erectile dysfunction (ED) are related to endothelial dysfunction. Elevated asymmetrical dimethylarginine (ADMA) levels and ED are common in patients with increased cardiovascular risk. Our aim was to investigate whether ADMA has a predictive role for major adverse cardiovascular events (MACE) in acute coronary syndrome (ACS). The secondary aim of this study was to investigate whether severity of ED predicts MACE in these patients.

Material and methods

Follow-up data were available for severity of ED in 71 patients with ACS. Plasma ADMA levels were determined by ELISA in 57 patients. Erectile dysfunction was assessed by the International Index of Erectile Function-6 (IIEF-6) score. Major adverse cardiovascular events (reinfarction, all-cause hospitalisation, stroke and all-cause death) was evaluated after a median of 10 months.

Results

Severe ED had no significantly increased hazard ratio for cardiovascular events compared with mild, mild to moderate, and moderate ED (0.259 [95% CI 0.041–1.6], p = 0.147; 0.605 [95% CI 0.095–3.8], p = 0.594; 0.980 [95% CI 0.233–4.1], p = 0.978; and 0.473 [95% CI 0.052–1.3], p = 0.508). The patients who had ADMA levels ≥ 0.32 µmol/l had no significantly increased hazard ratio for cardiovascular events compared with patients who had ADMA levels < 0.32 µmol/l (2.018 [95% CI 0.615–6.6], p = 0.247).

Conclusions

Severity of ED and ADMA did not increase the risk of cardiovascular events in follow-up patients with ACS in our study. Larger prospective studies are necessary to evaluate whether ADMA predicts cardiovascular events in patients with ACS.     

Interleukin-1B-31T/C promoter polymorphism and chronic obstructive pulmonary disease risk: a meta-analysis

Introduction

The role of interleukin (IL)-1β –31T/C promoter polymorphism in the pathogenesis of chronic obstructive pulmonary disease (COPD) has been studied with inconsistent results. This meta-analysis was performed to assess the association of IL-1β –31T/C promoter polymorphism with COPD susceptibility.

Material and methods

Published case-control studies from PubMed and China National Knowledge Infrastructure (CNKI) databases were retrieved. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated.

Results

Six case-control studies were included in this meta-analysis. The pooled effect size showed that IL-1β -31T/C was significantly associated with COPD susceptibility in an overdominant genetic model (CC+TT vs. TC, OR: 0.77, 95% CI: 0.63–0.94), indicating that homozygotes (CC and TT) had a decreased risk for COPD compared with heterozygotes (TC). In the subgroup analysis by ethnicity, the results indicated that IL-1β –31T/C was significantly correlated with COPD susceptibility in Asians (overdominant model, OR: 0.75, 95% CI: 0.61–0.93), further suggesting a protective role of IL-1β –31T/C in COPD pathogenesis in Asians. Moreover, after excluding the study without Hardy-Weinberg equilibrium, the pooled results were robust and no publication bias was found in this study.

Conclusions

This meta-analysis suggests that IL-1β –31T/C promoter polymorphism confers protection against COPD in Asians.     

Association of the Alu insertion polymorphism in the progesterone receptor gene with breast cancer in a Mexican population

Introduction

The progesterone receptor (PR) gene plays an important role in reproduction-related events. Data on polymorphisms in the PR gene have revealed associations with cancer, particularly for the Alu insertion polymorphism, which has been suggested to affect progesterone receptor function and contribute to tumor promotion in the mammary gland.

Material and methods

We examined the role of the Alu insertion polymorphism in the PR gene by comparing the genotypes of 209 healthy Mexican women with those of 481 Mexican women with breast cancer (BC).

Results

The genotype frequencies observed in the controls and BC patients were 0% and 4% for T2/T2 (Alu insertion), 16% and 21% for T1/T2, and 84% and 75% for T1/T1 (Alu deletion), respectively. The obtained odds ratio (OR) was 1.7, with a 95% confidence interval (95% CI) of 1.1–2.6, p = 0.009, for the T1/T2–T2/T2 genotypes. The association was also evident when the distributions of the T1/T2–T2/T2 genotypes in patients in the following categories were compared: obesity grade II (OR = 1.81, 95% CI: 1.03–3.18, p = 0.039) and the chemotherapy response (OR = 1.91, 95% CI: 1.27–3.067, p = 0.002).

Conclusions

The T1/T2–T2/T2 genotypes of the Alu insertion polymorphism in the PR gene are associated with BC susceptibility in the analyzed Mexican population.     

Efficacy and tolerability of renzapride in irritable bowel syndrome: a meta-analysis of randomized,controlled clinical trials including 2528 patients

Introduction

By targeting different subtypes of 5-hydroxytryptamine (5HT) receptors in the gastrointestinal (GI) tract, several drugs have been introduced for the management of irritable bowel syndrome (IBS). Renzapride is a full agonist for 5HT4 receptor and an antagonist to 5HT2b and 5HT3 receptors which is thought a promising therapeutic agent for constipation predominant IBS (C-IBS) patients due to its accelerating effect on the GI tract. In this meta-analysis, our aim was to evaluate the efficacy and tolerability of renzapride in the management of IBS.

Material and methods

A search was done from 1992 to February 2013 for placebo-controlled trials that investigated the efficacy of renzapride in IBS.

Results

Relative risk (RR) for clinical efficacy in IBS patients treated for 5 weeks or less comparing renzapride to placebo was 1.07 (95% CI = 0.89–1.29, p = 0.38). This value for IBS patients treated for more than 5 weeks was 1.04 (95% CI = 0.78–1.239, p = 0.77). The RR for clinical efficacy in IBS patients treated with renzapride (4 mg) for 5 weeks or less and more than 5 weeks in comparison to placebo was 1.2 (95% CI = 0.97–1.48, p = 0.1) and 1.16 (95% CI = 0.98–1.37, p = 0.08), respectively, which were statistically non-significant but clinically important. The analysis of tolerability demonstrated that amongst different reported adverse effects, renzapride caused diarrhea more than placebo (RR = 1.61 with a 95% CI = 1.16–2.24, p = 0.004). The RR for withdrawals from renzapride compared to placebo was 1.58 (95% CI = 1.26–2.07, p = 0.0007).

Conclusions

Renzapride is not superior to placebo in relieving IBS symptoms and causes significant incidences of diarrhea and drop-outs due to adverse effects in treated patients vs. placebo. Thus, this medicine might be a cost burden to patients without providing good effectiveness.     

Genetic variability and the risk of myocardial infarction in Poles under 45 years of age

Introduction

Myocardial infarction is caused by the obstruction of an artery in places of atherosclerosis plaque rupture. Endothelial cells during their activation express chemoattractant and adhesion molecules whereas infiltrating inflammatory cells produce enzymes, predisposing a lesion to rupture.

Material and methods

We investigated the correlation between polymorphisms in the human genes E-selectin (Ser128Arg), ICAM1 (K469E), OLR1 (K167N), MMP1 (1G/2G) and MMP3 (−1612 5A/6A) and the risk of MI in young Poles under 45 years. There was no significant difference in the frequency of single nucleotide polymorphism (SNP) of the studied genes E-selectin (Ser128Arg), ICAM1 (K469E), OLR1 (K167N) and MMP3 (−1612 5A/6A) between patients with MI and controls.

Results

The analysis of the association of the 1G2G polymorphism with the risk of myocardial infarction indicated an odds ratio (OR) of 5.68 (95% confidence interval [95% CI] 2.60 to 12.36). Other factors associated with myocardial infarction were: smoking (OR 4.12; 95% CI 1.63–10.44), male sex (OR 16.02; 95% CI 5.90–43.46), hypercholesterolaemia (OR 2.74; 95% CI 1.29–5.83) and arterial hypertension (OR 4.56; 95% CI 1.66–14.47).

Conclusions

We found that only MMP1 1G/2G polymorphism is associated with myocardial infarction in the Polish population of individuals younger than 45 years. Clinical factors seemed to play a greater role in the analysed group.     

Vitamin D intake and type 2 diabetes risk: a meta-analysis of prospective cohort studies

Background

The findings form studies on the relationship between vitamin D and type 2 diabetes were inconsistent.

Objectives

To elucidate the association between vitamin D consumption and type 2 diabetes risk by conducting a meta-analysis.

Methods

We conducted a systematic literature search to identify prospective cohort studies of vitamin D intake and type 2 diabetes risk prior to November 2012. Eligible studies were retrieved via both computer searches and manual review of references. The summary risk estimates were calculated based on the highest versus the lowest categories.

Results

Meta-analysis of 4 prospective cohort studies involving 187, 592 participants and 9, 456 incident cases showed an absence of significant association between total vitamin D intake and type 2 diabetes risk. The combined RR was 0.93 (95% CI: 0.85–1.01). The associations were similar for subgroup analyses, a combined RR respectively was 0.94 (95% CI: 0.77–1.08), 0.91 (95% CI: 0.77–1.08), 0.93 (95% CI: 0.84–1.02), and 0.92 (95% CI: 0.84–1.01) for the intake of dietary vitamin D, supplemental vitamin D, total vitamin D in USA and total vitamin D for women only.

Conclusions

Our results support that there was no association between vitamin D intake and type 2 diabetes.     

Causes and prevalence of inadequate pulmonary function testing among patients with systemic sclerosis

Introduction

Spirometry is a screening tool for evaluating the degree of restrictive lung disease in systemic sclerosis (SSc). Observations indicated that some patients could not complete the test. The aim of the study was to identify the prevalence, causes and clinical predictors of an inadequate pulmonary function test (PFT) in SSc.

Material and methods

A cross-sectional study was performed among SSc patients over 18 years old followed up at Srinagarind Hospital, Khon Kaen, Thailand, during January 2006–December 2012. The adequacy of the PFT was based on the acceptable blow criteria as set out by the American Thoracic Society and the European Respiratory Society 2005 Standardizations of Spirometry.

Results

Two hundred and forty-nine patients were included (female to male ratio was 2 : 1). The mean age at performing PFT was 51.4 ±11.1 years (range: 19.6–79.5). Median duration of disease at performing PFT was 2 years (IQR: 0.6–4.4). Inadequate PFT occurred in 73 cases (prevalence 29.3%: 95% CI: 23.6–35.0); the majority (60 cases; 82.2%) had an expiration time < 6 s and the others were due to plateau < 1 s (11 cases; 15%), air leak around mouth piece (1 case; 1.4%) and hesitation (1 case; 1.4%). Thirteen of 73 (17.8%) had an unusable graph with the overall prevalence of 5.2% (95% CI: 2.4–8.0). The factor associated with inadequate PFT was docy mass index (BMI) < 18.5 kg/m² (OR = 2.17: 95% CI: 1.49–3.17); the same factor was associated with an unusable graph, which was confirmed by the multivariate analysis (OR = 5.21; 95% CI: 1.60–16.95).

Conclusions

One-third of Thai SSc patients had an inadequate pulmonary function test – the majority because of inadequate time for expiring. Low BMI influenced the effectiveness of the test, leading to an incomplete graph for evaluating lung disease in SSc.     

Meta-analysis of randomized trials on access site selection for percutaneous coronary intervention in ST-segment elevation myocardial infarction

Introduction

Superior outcomes with transradial (TRPCI) versus transfemoral coronary intervention (TFPCI) in the setting of acute ST-segment elevation myocardial infarction (STEMI) have been suggested by earlier studies. However, this effect was not evident in randomized controlled trials (RCTs), suggesting a possible allocation bias in observational studies. Since important studies with heterogeneous results regarding mortality have been published recently, we aimed to perform an updated review and meta-analysis on the safety and efficacy of TRPCI compared to TFPCI in the setting of STEMI.

Material and methods

Electronic databases were searched for relevant studies from January 1993 to November 2012. Outcome parameters of RCTs were pooled with the DerSimonian-Laird random-effects model.

Results

Twelve RCTs involving 5,124 patients were identified. According to the pooled analysis, TRPCI was associated with a significant reduction in major bleeding (odds ratio (OR): 0.52 (95% confidence interval (CI) 0.38–0.71, p < 0.0001)). The risk of mortality and major adverse events was significantly lower after TRPCI (OR = 0.58 (95% CI: 0.43–0.79), p = 0.0005 and OR = 0.67 (95% CI: 0.52–0.86), p = 0.002 respectively).

Conclusions

Robust data from randomized clinical studies indicate that TRPCI reduces both ischemic and bleeding complications in STEMI. These findings support the preferential use of radial access for primary PCI.     

The association between the 844ins68 polymorphism in the CBS gene and breast cancer

Introduction

The cystathionine beta synthase (CBS) gene plays an important role in homocysteine metabolism because it catalyzes the first step of the transsulfuration pathway, during which homocysteine is converted to cystathionine. Polymorphisms of CBS have been associated with cancer.

Material and methods

We examined the role of the 844ins68 polymorphism by comparing the genotypes of 371 healthy Mexican women with the genotypes of 323 Mexican women with breast cancer (BC).

Results

The observed genotype frequencies for controls and BC patients were 1% and 2% for Ins/Ins, 13% and 26% for W/Ins, and 86% and 72% for W/W, respectively. We found that the odds ratio (OR) was 2.2, with a 95% confidence interval (95% CI) of 1.5–3.3, p = 0.0001. The association was also evident when comparing the distribution of the W/Ins-Ins/Ins genotypes in patients in the following categories: 1) menopause and high γ-glutamyltransferase (GGT) levels (OR of 2.17, 95% CI: 1.17–4.26, p = 0.02), 2) chemotherapy response and high lactate dehydrogenase (LDH) levels (OR 2.2, 95% CI: 1.08–4.4, p = 0.027), 3) chemotherapy response and high GGT levels (OR 2.46, 95% CI: 1.2–4.8, p = 0.007), and 4) body mass index (BMI) and III–IV tumor stage (OR 3.2, 95% CI: 1.2–8.3, p = 0.013).

Conclusions

We conclude that the genotypes W/Ins-Ins/Ins of the 844ins68 polymorphism in the CBS gene contribute significantly to BC susceptibility in the analyzed sample from the Mexican population.     

Lipid profile and glucose changes after supplementation with astaxanthin: a systematic review and meta-analysis of randomized controlled trials

Introduction

Many studies have shown that oral supplementation with astaxanthin may be a novel potential treatment for inflammation and oxidative stress in cardiovascular diseases, but evidence of the effects on lipid profile and glucose is still inconclusive. Therefore, we performed a meta-analysis to evaluate the efficacy of astaxanthin supplementation on plasma lipid and glucose concentrations.

Material and methods

The search included PubMed, Cochrane Library, Scopus, and EMBASE (up to November 27, 2014) to identify randomized controlled trials (RCTs) investigating the effects of astaxanthin supplementation on lipid profile and glucose levels. Two independent reviewers extracted data on study characteristics, methods and outcomes.

Results

Seven studies meeting inclusion criteria with 280 participants were selected for this meta-analysis; 163 participants were allocated to the astaxanthin supplementation group and 117 to the control group. A random-effect meta-analysis of data from 7 RCTs (10 treatment arms) did not show any significant effect of supplementation with astaxanthin on plasma concentrations of total cholesterol (weighted mean difference (WMD): –1.52 mg/dl, 95% CI: –8.69 to –5.66, p = 0.679), LDL-C (WMD: +1.25 mg/dl, 95% CI: –6.70 to +9.21, p = 0.758), HDL-C (WMD: +1.75 mg/dl, 95% CI: –0.92 to +4.42, p = 0.199), triglycerides (WMD: –4.76 mg/dl, 95% CI: –21.52 to +12.00, p = 0.578), or glucose (WMD: –2.65 mg/dl, 95% CI: –5.84 to +0.54, p = 0.103). All these effect sizes were robust, and omission of any of the included studies did not significantly change the overall estimate.

Conclusions

This meta-analysis of data from 10 RCT arms did not indicate a significant effect of supplementation with astaxanthin on plasma lipid profile, but a slight glucose-lowering effect was observed. Further, well-designed trials are necessary to validate these results.     

The –553 T/A polymorphism in the promoter region of the FGF2 gene is associated with increased breast cancer risk in Polish women

Introduction

Fibroblast growth factor-2 (FGF2) is an important signalling molecule contributing to angiogenesis, tumour growth and progression and its expression is implicated in breast cancer (BC) development. We investigated whether –553 T/A FGF2 gene polymorphism is associated with the risk and progression of BC in Polish women.

Material and methods

The –553 T/A polymorphism was genotyped in 230 breast cancer patients and 245 control subjects, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach. Moreover, FastQuant human angiogenesis array was used to measure FGF2 levels in tumour (n = 127) and serum (n = 76) samples.

Results

The T/A genotypes (OR = 2.12, 95% CI: 1.20–3.74) (p = 0.08) and the combined heterozygotes T/A and homozygote A/A (OR = 2.18, 95% CI: 1.24–3.83) (p = 0.006) had an increased risk of BC. The median FGF2 levels in the tumours of A allele carriers were significantly increased compared to T/T patients, whereas in serum FGF2 levels were hardly altered among different genotype carriers. Significantly higher frequency of A allele was found in patients with lymph node metastases (OR = 2.53; 95% CI: 1.23–5.17) (p = 0.009) and human epidermal growth factor receptor 2 positive tumour (OR = 3.22, 95% CI: 1.49–6.99) (p = 0.002). Furthermore, Kaplan-Meier survival analysis showed that the A allele predicted worse disease-free survival (DFS) in BC patients.

Conclusions

Our study shows for the first time that the –553 T/A FGF2 gene polymorphism may be associated with a risk of BC developing and progression in Polish women and may have prognostic value for the assessment of BC high-risk groups.     

Anti-epidermal growth factor receptor monoclonal antibody-based therapy for metastatic colorectal cancer: a meta-analysis of the effect of PIK3CA mutations in KRAS wild-type patients

Introduction

We conducted a meta-analysis to dissect the association between PIK3CA mutations (exon 9 and exon 20) and resistance to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MoAbs) in KRAS wild-type metastatic colorectal cancer (mCRC) patients.

Material and methods

In 11 previously published studies, 864 cancer patients were treated with cetuximab or panitumumab-based therapy. Primary outcomes included objective response (complete response + partial response vs. stable disease + progressive disease), progression-free survival (PFS), and overall survival (OS). We calculated the odds ratio (OR) or hazard ratio (HR) with 95% confidence intervals (CIs) to estimate the risk or hazard. We found consistent and clinically substantial risk or hazard for objective response, PFS, and OS in the cetuximab or panitumumab-treated mCRC patients.

Results

PIK3CA mutations as a whole were associated with reduced response and poor PFS and OS in KRAS wild-type mCRC patients (objective response: OR = 0.42 and 95% CI 0.23–0.75; PFS: HR = 1.54 and 95% CI 1.13–2.09; and OS: HR = 1.4 and 95% CI 1.02–1.91). PIK3CA exon 9 mutations had no effect, whereas exon 20 mutations were associated with a worse outcome compared with wild types, with an OR of 0.21 (95% CI 0.05–0.93).

Conclusions

PIK3CA mutations as a whole might be useful prognostic factors for assessing clinical outcomes of anti-EGFR MoAb-based chemotherapies in KRAS wild-type mCRC patients. In particular, PIK3CA exon 20 mutations were significantly associated with lack of response.     

Tumor necrosis factor-α antibodies (infliximab,adalimumab and certolizumab) in Crohn's disease: systematic review and meta-analysis

Introduction

This meta-analysis compares the effectiveness and safety of tumor necrosis factor α (TNF-α) antibodies (infliximab, adalimumab and certolizumab) with either a placebo or each of them in the treatment of Crohn''s disease (CD).

Material and methods

A systematic review of literature published up to November 2012 was performed and a meta-analysis of identified studies was carried out. We searched the following databases: PubMed, EMBASE, The Cochrane Library and others. Only randomized or clinical controlled trials were included.

Results

Nineteen clinical trials fulfilled the established criteria (5 studies for infliximab vs. placebo, 6 for each adalimumab or certolizumab vs. placebo and 2 comparing infliximab with adalimumab). The results of meta-analysis showed that anti-TNF therapy in patients with CD is safe and statistically significantly more effective when compared with the placebo for induction of remission at week 4 (RB = 1.90, 95% CI: 1.55–2.33, p < 0.00001), maintenance of remission at weeks 20–30 (RB = 1.86, 95% CI: 1.61–2.15, p < 0.00001) and at weeks 48–56 (RB = 2.75, 95% CI: 2.13–3.54, p < 0.00001) in patients who responded to the induction therapy and patients randomized before the induction. Anti-TNF agents were also superior to the placebo in fistula healing (during short-term induction, as well as long-term maintenance) and inducing CR-70 but not CR-100 at week 4. Moreover, the anti-TNF therapy had a significant effect on achieving both CR-70 and CR-100 during long-term maintenance.

Conclusions

Infliximab, adalimumab and certolizumab are effective as both induction and maintenance therapy in moderate to severe Crohn''s disease in adults, including patients with fistulas. The safety profile was acceptable.     

Prognostic role of SPARC expression in gastric cancer: a meta-analysis

Introduction

Secreted protein acidic and rich in cysteine (SPARC) is involved in regulating cell adhesion, proliferation, migration, and tissue remodeling. We performed a meta-analysis to evaluate the association between SPARC expression and the clinicopathologic features and outcomes of gastric cancer patients.

Material and methods

Publications that assessed the clinical or prognostic significance of SPARC in gastric cancer up to October 2013 were identified. A meta-analysis was performed to clarify the association between SPARC expression and clinical outcomes.

Results

Ten studies, including 1417 cases, met the inclusion criteria. The data were analyzed and the results show that SPARC is not significantly associated with the depth of gastric cancer invasion (odds ratio (OR) = 1.17, 95% confidence interval (CI): 0.60–2.29, Z = 0.47, p = 0.64) or tumor differentiation (OR = 0.59, 95% CI: 0.22–1.58, Z = 1.06, p = 0.29). Moreover, SPARC was not significantly correlated with lymph node metastasis (OR = 0.72, 95% CI: 0.37–1.41, Z = 0.96, p = 0.34). However, SPARC overexpression was highly correlated with reduced overall survival (relative risk (RR) = 1.78, 95% CI: 1.52–2.09, Z = 7.10, p = 0.43).

Conclusions

The SPARC may play an important role in the progression of gastric cancer, and SPARC overexpression is closely correlated with poor patient survival. The SPARC is a potential clinical marker for the survival of gastric cancer patients; however, well-designed prospective studies are needed to confirm these findings.