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.     

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.     

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.     

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.     

Role of immunosuppressive therapy and predictors of therapeutic effectiveness and renal outcome in IgA nephropathy with proteinuria

Introduction

The aim of the study was to analyze the role of immunosuppressive therapy and identify independent predictors of therapeutic effectiveness and outcome in IgA nephropathy (IgAN) patients with proteinuria.

Material and methods

Two hundred and six IgAN patients with proteinuria (1–3.5 g/day) were included between January 2005 and December 2011, and divided into two groups: group A (n = 125), receiving renin-angiotensin system blockade therapy alone; and group B (n = 81), combining the above with immunosuppressive therapy. The clinicopathological features, response and safety were recorded. In univariate and multivariate models, the factors that influence response to therapy and renal outcome, especially pathologic features, were analyzed.

Results

The patients in group B presented more severe proteinuria and hypoalbuminemia with more severe hematuria (p < 0.05) but no significant difference in the pathologic changes compared with group A. After follow-up, the response rate was higher in group B than in group A (p < 0.001). No pathologic feature or clinical parameter apart from steroid therapy (HR = 0.500, 95% CI: 0.304–0.821, p = 0.006) was strongly associated with therapeutic effectiveness. Endocapillary hypercellularity (HR = 2.849, 95% CI: 1.244–6.524, p = 0.013) seemed to be an independent predictor of poor response to steroid therapy. The renal survival rate was not significantly different between the two groups (p = 0.074). Estimated glomerular filtration rate at baseline may be an independent predictor of renal outcome.

Conclusions

Steroid therapy could be an effective therapy in proteinuric IgAN patients, and endocapillary hypercellularity seemed to predict poor response to steroid. Renal function at baseline rather than treatment strategies and pathologic features may be independently associated with renal survival.     

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.     

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.     

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.     

Sipuleucel-T immunotherapy for castration-resistant prostate cancer. A systematic review and meta-analysis

Introduction

Sipuleucel-T is a novel active cellular immunotherapy for the treatment of asymptomatic or minimally symptomatic metastatic castrate-resistant prostate cancer (mCRPC). It is assumed to be associated with less adverse events than conventional docetaxel-based chemotherapy.

Material and methods

A systematic review of literature published between January, 1 1966 and February, 6 2012 was performed to assess the efficacy and safety of sipuleucel-T in patients with mCRPC. Databases were searched: Medline, EMBASE, Cochrane, CancerLit as well as ASCO and ESCO websites.

Results

Three randomized clinical trials with a total of 737 participants fulfilled established criteria. The overall survival of patients who received sipuleucel-T in comparison to the control group was significantly longer with a hazard ratio (HR) of 0.73 (95% CI: 0.61-0.88; p = 0.001). Time to disease progression was not prolonged using sipuleucel-T compared to placebo, HR = 0.89 (95% CI: 0.75-1.05; p = 0.18). Relative benefit (RB) of serum PSA level reduction of at least 50% for sipuleucel-T compared to placebo did not meet statistical significance, RB = 1.97 (95% CI: 0.48-8.14; p = 0.38). The safety population consisted of 729 patients with mCRPC. Compared to the control group, the pooled relative risks (RR) of all adverse events – RR = 1.03 (95% CI: 1.00-1.05; p = 0.06), grade 3 to 5 adverse events – RR = 0.98 (95% CI: 0.79-1.22; p = 0.86) and cerebrovascular events – RR = 1.93 (95% CI: 0.73-5.09; p = 0.18) were not significantly higher for men treated with sipuleucel-T.

Conclusions

The use of sipuleucel-T prolonged the overall survival among men with mCRPC. No effect on time to disease progression was observed and the safety profile was acceptable.     

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.     

–308 G/A TNF-α gene polymorphism influences the course of basal cell carcinoma in a Polish population

Introduction

The etiopathogenesis of basal cell carcinoma (BCC) is multifactorial. The TNF-α gene seems to be an interesting gene candidate for BCC susceptibility because of the proinflammatory and immunosuppressive properties of its product. The aim of the study was to assess the frequency of –308 G/A and –238 G/A gene polymorphisms in the TNF-α gene and serum levels of cytokine in patients with BCC.

Material and methods

The study included 176 (94 women, 82 men) patients with BCC and 261 healthy volunteers. –308 G/A and –238 G/A TNF-α polymorphisms were analyzed using the amplification refractory mutation system-polymerase chain reaction method (ARMS-PCR). Serum concentrations of TNF-α were measured using ELISA.

Results

There was no statistically significant association between allele, genotype and haplotype frequencies in BCC patients in comparison with controls. Occurrence of the –308 TNF-α A allele or GA genotype in the group of patients with BCC increases risk of recurrence of tumor recurrence (OR = 4.8, 95% CI: 1.6–13.9, p = 0.004 and OR = 4.97, 95% CI: 1.7–14.5, p = 0.004). Moreover, –308 TNF-α GG genotype decreased risk of recurrence (OR = 0.2, 95% CI: 0.07–0.6, p = 0.004). The –238/–308 GA haplotype was connected with increased risk of recurrence (OR = 4.36, 95% CI: 1.49–12.7, p = 0.007). We also found significantly higher TNF-α levels among BCC patients in comparison with controls (p = 0.004).

Conclusions

The obtained results did not confirm the role of the –308 G/A and –238 G/A TNF-α gene polymorphisms in BCC development, but the presence of the A allele or GA genotype in –308 G/A TNF-α gene polymorphism may have an impact on the course of the disease.     

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.     

Predictive factors of proximal advanced neoplasia in the large bowel

Introduction

The aim of the study was to evaluate the impact of sex, age, family history and distal findings on the risk of proximal advanced neoplasia (cancer or advanced adenoma) in the large bowel.

Material and methods

Records for 10 111 asymptomatic participants of the Colonoscopy Screening Program (CSP), recruited from the Warsaw region between 2000 and 2004, were analyzed. A multivariate logistic regression model was used to estimate the impact of sex, age, family history and most advanced distal lesions on the occurrence of proximal advanced neoplasia. To enhance comparability of the study two definitions of the proximal colon were applied – either the splenic flexure (1^st) or the bend between the descending and sigmoid colon (2^nd definition) represented the boundary.

Results

One hundred and thirty-three (1^st) and 167 patients (2^nd definition) were found to have at least one advanced neoplastic lesion in the proximal part, respectively. Eleven and 14 patients were found to have carcinoma, while in 130 and 163 patients at least one proximal advanced adenoma appeared. Men were at twice as high risk of having advanced neoplasia in the proximal colon than women (OR = 1.94, 95% CI: 1.31–2.87, p = 0.001 or OR = 1.69, 95% CI: 1.20–2.40, p = 0.003, respectively). The presence of distal advanced neoplastic lesions was associated with 3.5 times higher risk of proximal advanced neoplasia (OR = 3.58, 95% CI: 2.00–6.43, p < 0.0001 or OR = 3.41, 95% CI: 1.95–5.96, p < 0.0001), respectively.

Conclusions

The results may confirm some limitation of flexible sigmoidoscopy in the screening settings in comparison with colonoscopy, at least in men and people with distal advanced neoplasia.     

Toll-like receptor 4 gene polymorphisms and susceptibility to colorectal cancer: a meta-analysis and review

Introduction

Many case-control studies have investigated the association between toll-like receptor 4 (TLR4) Asp299Gly and Thr399Ile polymorphisms and risk of colorectal cancer (CRC). However, published data are still conflicting.

Material and methods

A systematic search was conducted in the electronic databases of PubMed, MEDLINE, EMBASE, Web of Science and CNKI between 2000 and 2014. The associations between TLR4 polymorphisms and CRC susceptibility were assessed by pooled odds ratios (ORs) and 95% confidence intervals (95% CI) in fixed or random effects models.

Results

In total nine case-control studies were identified in this meta-analysis. For TLR4 Asp299Gly polymorphism, 9 studies included 1198 cases and 1290 controls. The GG genotype carriers had higher risk for developing CRC than AA + GA genotype carriers (OR = 1.95, 95% CI: 1.00–3.77, p = 0.05). No association was found in other genetic models (p > 0.05). Analysis stratified by ethnicity showed no association in any genetic models among the Asian or Caucasian population. For TLR4 Thr399Ile polymorphism, 6 studies contained 619 cases and 632 controls. The overall analysis showed significantly increased risk in TT homozygote carriers compared to CC homozygote (OR = 4.99, 95% CI: 1.41–17.65, p = 0.01) and C carriers (TC + CC) (OR = 4.50, 95% CI: 1.27–15.87, p = 0.02). In terms of analyses stratified by race, a significant association was found in each genetic model among the Asian population, rather than the Caucasian group.

Conclusions

The GG homozygote carriers of TLR4 Asp299Gly and TT homozygote carriers of TLR4 Thr399Ile polymorphisms might be correlated with an increased risk of CRC, suggesting they may serve as genetic risk factors for CRC.     

The role of gender in patients with diffuse large B cell lymphoma treated with rituximab-containing regimens: a meta-analysis

Introduction

Diffuse large B cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL). Although gender has not been included in prognostic systems, male gender has been found as a bad prognostic indicator in Hodgkin lymphoma, follicular lymphoma and chronic lymphocytic leukemia. The relationship between gender and prognosis is not clear in patients with DLBCL treated with rituximab-containing regimens. The aim of this meta-analysis is to determine the prognostic/predictive role of gender in patients with DLBCL treated with rituximab-containing regimens.

Material and methods

We systematically searched for studies investigating the relationships between gender and prognosis in DLBCL treated with rituximab-containing regimens. After careful review, survival data were extracted from eligible studies. A meta-analysis was performed to generate combined hazard ratios for overall survival, disease-free survival (DFS) and event-free survival (EFS).

Results

A total of 5635 patients from 20 studies were included in the analysis. Our results showed that male gender was associated with poor prognosis in terms of overall survival (OS) (hazard ratio (HR) = 1.155; 95% confidence interval (CI): 1.037–1.286; p < 0.009). The pooled hazard ratio for DFS and EFS showed that male gender was not statistically significant (HR = 1.219; 95% CI: 0.782–1.899; p = 0.382, HR = 0.809; 95% CI: 0.577–1.133; p = 0.217).

Conclusions

The present meta-analysis indicated male gender to be associated with a poor prognosis in patients with DLBCL treated with rituximab-containing regimens.     

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.     

Lack of reliable clinical predictors to identify obstructive sleep apnea in patients with hypertrophic cardiomyopathy

OBJECTIVE:

Obstructive sleep apnea is common among patients with hypertrophic cardiomyopathy and may contribute to poor cardiovascular outcomes. However, obstructive sleep apnea is largely unrecognized in this population. We sought to identify the clinical predictors of obstructive sleep apnea among patients with hypertrophic cardiomyopathy.

METHODS:

Consecutive patients with hypertrophic cardiomyopathy were recruited from a tertiary University Hospital and were evaluated using validated sleep questionnaires (Berlin and Epworth) and overnight portable monitoring. Ninety patients (males, 51%; age, 46±15 years; body mass index, 26.6±4.9 kg/m²) were included, and obstructive sleep apnea (respiratory disturbance index ≥15 events/h) was present in 37 patients (41%).

RESULTS:

Compared with the patients without obstructive sleep apnea, patients with obstructive sleep apnea were older and had higher body mass index, larger waist circumference, larger neck circumference, and higher prevalence of atrial fibrillation. Excessive daytime sleepiness (Epworth scale) was low and similar in the patients with and without obstructive sleep apnea, respectively. The only predictors of obstructive sleep apnea (using a logistic regression analysis) were age ≥45 years (odds ratio [OR], 4.46; 95% confidence interval [CI 95%], 1.47–13.54; p = 0.008) and the presence of atrial fibrillation [OR, 5.37; CI 95%, 1.43–20.12; p = 0.013].

CONCLUSION:

Consistent clinical predictors of obstructive sleep apnea are lacking for patients with hypertrophic cardiomyopathy, which suggests that objective sleep evaluations should be considered in this population, particularly among elderly patients with atrial fibrillation.     

Interleukin-1β (3953/4) C→T polymorphism increases the risk of chronic periodontitis in Asians: evidence from a meta-analysis of 20 case-control studies

Introduction

To investigate the association of the interleukin-1β (IL-1β) (3953/4) C→T polymorphism with chronic periodontitis (CP) in Asians.

Material and methods

Systematic searches of electronic databases and hand searching of references were performed, including PubMed, Embase, the Cochrane Library, and the Chinese National Knowledge Infrastructure (CNKI). Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the associations. Publication bias was tested by Egger''s test. Sensitivity analysis was conducted by limiting the meta-analysis studies conforming to Hardy-Weinberg equilibrium (HWE). Data analyses were carried out using RevMan 6.0.

Results

A meta-analysis was performed on 20 published case-control studies, including 1,656 CP cases and 1,498 healthy controls. The pooled OR was 1.60 (95% CI = 1.02–2.52, p = 0.04) for the T allele carriers (TT + CT) compared with CC and 1.60 (95% CI = 1.06–2.42, p = 0.02) for T vs. C. Subgroup analysis by country revealed significant risks of CP among Indians carrying the T allele (TT vs. CC: OR = 3.88, 95% CI = 1.77–8.50, p = 0.0007).

Conclusions

The analysis showed that IL-1β (3953/4) C→T polymorphism probably increases the risk of CP in Asians, and the IL-1β+3954 TT genotype may be associated with a strongly increased risk of CP in Indians, but not in Chinese.     

Habitual Sleep Duration and Insomnia and the Risk of Cardiovascular Events and All-cause Death: Report from a Community-Based Cohort

Study Objectives:

To investigate the relationship between sleep duration and insomnia severity and the risk of all-cause death and cardiovascular disease (CVD) events

Design:

Prospective cohort study

Setting:

Community-based

Participants:

A total of 3,430 adults aged 35 years or older

Intervention:

None

Measurements and Results:

During a median 15.9 year (interquartile range, 13.1 to 16.9) follow-up period, 420 cases developed cardiovascular disease and 901 cases died. A U-shape association between sleep duration and all-cause death was found: the age and gender-adjusted relative risks (95% confidence interval [CI]) of all-cause death (with 7 h of daily sleep being considered for the reference group) for individuals reporting ≤ 5 h, 6 h, 8 h, and ≥ 9 h were 1.15 (0.91–1.45), 1.02 (0.85–1.25), 1.05 (0.88–1.27), and 1.43 (1.16–1.75); P for trend, 0.019. However, the relationship between sleep duration and risk of CVD were linear. The multivariate-adjusted relative risk (95% CI) for all-cause death (using individuals without insomnia) were 1.02 (0.86–1.20) for occasional insomnia, 1.15 (0.92–1.42) for frequent insomnia, and 1.70 (1.16–2.49) for nearly everyday insomnia (P for trend, 0.028). The multivariate adjusted relative risk (95% CI) was 2.53 (1.71–3.76) for all-cause death and 2.07 (1.11–3.85) for CVD rate in participants sleeping ≥9 h and for those with frequent insomnia.

Conclusions:

Sleep duration and insomnia severity were associated with all-cause death and CVD events among ethnic Chinese in Taiwan. Our data indicate that an optimal sleep duration (7–8 h) predicted fewer deaths.

Citation:

Chien K; Chen P; Hsu H; Su T; Sung F; Chen M; Lee Y. Habitual sleep duration and insomnia and the risk of cardiovascular events and all-cause death: report from a community-based cohort. SLEEP 2010;33(2):177–184.