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.     

Association of a common genetic variant in prostate stem cell antigen with cancer risk

Introduction

Polymorphisms in the prostate stem cell antigen (PSCA) gene have been hypothesized to increase the genetic susceptibility to cancers. The common sequence variation in PSCA rs2294008 (C>T) has been implicated in cancer risk. However, results of the relevant published studies were somewhat underpowered and controversial in general.

Material and methods

To evaluate the role of PSCA rs2294008 (C>T) genotype in global cancer, we performed a pooled analysis of all the available published studies involving 22,817 cancer patients and 27,753 control subjects.

Results

The results showed evidence that PSCA rs2294008 (C>T) was associated with increased total cancer risk in the overall comparisons. Stratified analysis by cancer type indicated that PSCA rs2294008 T is associated with increased risk of gastric cancer (OR = 1.24, 95% CI = 1.09–1.42, p_{heterogeneity} < 0.001, I² = 88.0%) and bladder cancer (OR = 1.07, 95% CI = 1.04–1.11, p_{heterogeneity} = 0.108, I² = 55.0%) by allelic contrast. Furthermore, in stratified analysis by histological types of gastric cancer, this PSCA variant showed significant associations with diffuse type (OR = 1.81, 95% CI = 1.16–2.81, p_{heterogeneity} < 0.001, I² = 88.9%) but not intestinal type (OR = 1.29, 95% CI = 0.95–1.74, p_{heterogeneity} < 0.001, I² = 85.2%) in a dominant genetic model. Similar results were found in Asian and European descendents and population-based studies.

Conclusions

In all, our meta-analysis suggests that PSCA rs2294008 (C>T) may play allele-specific roles in cancer development. Further prospective studies with larger numbers of participants worldwide should be performed in different kinds of cancer and other descendents in more detail.     

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.     

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.     

The incidence of acute myocardial infarction in relation to overweight and obesity: a meta-analysis

Introduction

Epidemiological evidence suggests that overweight and obesity have been associated with acute myocardial infarction (AMI). However, data on this issue are controversial. This study aims to use meta-analysis to determine whether overweight and obesity are related to AMI.

Material and methods

We searched PubMed and Embase databases up to October 23^rd, 2013 for related literature. The association of overweight and obesity with AMI was assessed by odd ratio (OR) with 95% confidence interval (CI) as the effect size. Then subgroup analysis was performed according to gender, area and study type.

Results

Five primary studies (one cohort study and four case-control studies) were included in this meta-analysis involving 36 803 participants, 14 883 of whom had an AMI. There was a significant association between overweight and AMI (OR = 1.27, 95% CI: 1.21–1.33, p < 0.001). Similar results revealed a relation between obesity and AMI (OR = 1.22, 95% CI: 1.07–1.40, p = 0.003). Subgroup analysis showed that overweight and obesity were positively associated with AMI risk except for obese subjects in Europe. There was no publication bias (Begg''s test p = 0.972, Egger''s test p = 0.858).

Conclusions

Both overweight and obesity increased the incidence of AMI, and it is necessary to control weight to prevent AMI. A large number of studies is needed to explore the mechanisms that link overweight and obesity with AMI.     

Factors associated with suicidal behaviour among depressed patients in Penang,Malaysia

Introduction

This study aims to highlight the factors associated with suicidal behavior among patients with depressive disorders.

Material and methods

A retrospective (Jan 2002 – Dec 2007) evaluation of medical records was done at the psychiatric clinic at the Penang (Malaysia) Public Hospital. Data was analyzed using Statistical Package for Social Science SPSS version 13^®. Chi-square (χ²) test was used to assess the association among variables. Odds ratios were calculated. Multiple logistic regression was applied to identify the predictors for suicidal behavior.

Results

Of 298 patients, 99 patients reported having thoughts of suicide. Overall, female respondents, particularly Chinese, constituted the majority reporting suicidal thoughts (p = 0.01). Cigarette (p < 0.01) and alcohol use (p < 0.01) were found to be associated with suicidal ideation. Among patients with medical comorbidities, diabetics were at a high risk for suicidal thoughts (odds ratio – OR = 1.05, 95% confidence interval – CI 0.45-2.46). In terms of social problems, marital and relationship difficulties were the main risk factors (OR = 2.03, 95% CI: 1.16-3.58). The significant predictors for suicidal behavior were found to be smoking and alcohol use (adjusted R² = 0.39, F change = 75.55, p < 0.01).

Conclusions

Chinese females were found at higher risk of suicidal ideation, as were smokers and alcohol users. The elderly aged 50 and over were also at a higher risk, followed by adolescents and youths aged 15-24 years. Comorbid medical complications and social problems were other factors that may contribute to suicidal ideation among the patients with depressive disorders.     

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.     

–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.     

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.     

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.     

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.     

Predictors of In-Hospital Mortality Among Older Patients

OBJECTIVE:

The objective of this study was to determine predictors of in-hospital mortality among older patients admitted to a geriatric care unit.

INTRODUCTION:

The growing number of older individuals among hospitalized patients demands a thorough investigation of the factors that contribute to their mortality.

METHODS:

This was a prospective observational study implemented from February 2004 to October 2007 in a tertiary university hospital. A consecutive sample of 922 patients was evaluated for possible inclusion in this study. Patients hospitalized for palliative care, those who declined to participate, and those with incomplete data were excluded, resulting in a group of 856 patients aged 60 to 104 years. Bivariate and multivariate analyses were performed to determine associations between in-patient mortality and gender, age, length of stay, number of prescribed medications and diagnoses at admission, history of heart failure, neoplastic disease, immobility syndrome, delirium, infectious disease, and laboratory tests at admission (serum albumin and creatinine).

RESULTS:

The overall mortality rate was 16.4%. The following factors were associated with higher in-hospital mortality: delirium (OR=4.13, CI=2.65–6.44, P<.001), neoplastic disease (OR=3.38, CI=2.11–5.42, P<.001), serum albumin levels at admission <3.3mg/dL (OR=3.23, CI=2.03–5.13, P<.001), serum creatinine levels at admission ≥ 1.3mg/dL (OR=2.39, CI=1.53–3.72, P<.001), history of heart failure (OR=1.97, CI=1.20–3.22, P=.007), immobility (OR=1.84, CI=1.16–2.92, P =.009), and advanced age (OR=1.03, CI=1.01–1.06, P=.019).

CONCLUSIONS:

This study strengthens the perception of delirium as a mortality predictor among older inpatients. Cancer, immobility, low albumin levels, elevated creatinine levels, history of heart failure and advanced age were also related to higher mortality rates in this population.     

Obesity risk factors in a representative group of Polish prepubertal children

Introduction

The study aim was to evaluate risk factors of obesity in Polish children aged 7 to 9 years.

Material and methods

A representative group of 2571 children (1268 girls and 1303 boys) was randomly selected according to the European Childhood Obesity Group protocol. Weight and height were measured and body mass index (BMI) was calculated. A questionnaire was completed by the children''s parents with respect to behavioural and family-related risk factors of obesity. International Obesity Task Force criteria were used for classification of children''s obesity.

Results

Obesity was found in 3.7% of girls and 3.6% of boys. There was a statistically significant association between the prevalence of obesity in girls and their mother''s obesity: OR = 5.06 (1.96–13.05), p < 0.001, father''s obesity: OR = 5.19 (1.96–13.69), p < 0.001, and both parents’ obesity: OR = 5.43 (1.39–21.29), p = 0.01. Obesity in boys was significantly associated with mother''s obesity: OR = 5.6 (2.6–12.02), p < 0.001, father''s obesity: OR = 6.21 (2.89–13.37), p < 0.001, and both parents’ obesity: OR = 7.22 (2.44–31.33), p < 0.001. Skipping or irregular eating of breakfast was a risk factor for obesity in girls with OR = 2.71 (1.33–5.51), p = 0.005. Neither family income nor parents’ education level was related to their offspring''s obesity. TV watching, physical activity level and eating in fast food places were not significant risk factors for obesity.

Conclusions

Eating breakfast regularly seems to protect girls from obesity development while low physical activity is not a significant obesity risk factor in this age group for either boys or girls. This finding stresses the more important role of healthy diet than physical activity promotion in obesity prevention in prepubertal children.     

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.     

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.     

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.     

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.     

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.     

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.