Phosphatase and Tensin Homologue Genetic Polymorphisms and their Interactions with Viral Mutations on the Risk of Hepatocellular Carcinoma

Background:

Chronic hepatitis B virus (HBV) infection is the major cause of hepatocellular carcinoma (HCC). Some HBV mutants and dysregulation of phosphatase and tensin homolog (PTEN) may promote the development of HCC synergistically. We aimed to test the effects of PTEN genetic polymorphisms and their interactions with important HBV mutations on the development of HCC in HBV-infected subjects.

Methods:

Quantitative polymerase chain reaction was applied to genotype PTEN polymorphisms (rs1234220, rs2299939, rs1234213) in 1012 healthy controls, 302 natural clearance subjects, and 2011 chronic HBV-infected subjects including 1021 HCC patients. HBV mutations were determined by sequencing. The associations of PTEN polymorphisms and their interactions with HBV mutations with HCC risk were assessed using multivariate logistic regression analysis.

Results:

Rs1234220 C allele was significantly associated with HCC risk compared to healthy controls (adjusted odds ratio [AOR] = 1.35, 95% confidence interval [CI] = 1.07–1.69) and HCC-free HBV-infected subjects (AOR = 1.27, 95% CI = 1.01–1.57). rs1234220 C allele was significantly associated with increased frequencies of HCC-risk A1652G, C1673T, and C1730G mutations in genotype B HBV-infected subjects. Rs2299939 GT genotype was inversely associated with HCC risk in HBV-infected patients (AOR = 0.75, 95% CI = 0.62–0.92). The interaction of rs2299939 variant genotypes (GT+TT) with A3054T mutation significantly increased HCC risk (AOR = 2.41, 95% CI = 1.08–5.35); whereas its interaction with C3116T mutation significantly reduced HCC risk (AOR = 0.34, 95% CI = 0.18–0.66). These significant effects were only evident in males after stratification.

Conclusions:

PTEN polymorphisms and their interactions with HBV mutations may contribute to hepatocarcinogenesis in males. The host-virus interactions are important in identifying HBV-infected subjects who are more likely to develop HCC.     

Parents' Perception and their Decision on their Children's Vaccination Against Seasonal Influenza in Guangzhou

Background:Seasonal influenza epidemic occurs every year in Guangzhou,which can affect all age groups.Young children are the most susceptible targets.Parents can decide whether to vaccinate their child...     

ApaI,BsmI, FokI,and TaqI Polymorphisms in the Vitamin D Receptor Gene and Parkinson's Disease

Background:

The vitamin D receptor (VDR) gene has been identified as a candidate gene for susceptibility to Parkinson''s disease (PD), but results from genetic association studies to date are inconsistent. Here, we conducted a meta-analysis of published case-control studies to evaluate the association of the extensively studied VDR ApaI (G/T), BsmI (G/A), FokI (C/T), and TaqI (T/C) gene polymorphisms with risk of PD.

Methods:

Electronic search at PubMed, EMBASE, EBSCO, China National Knowledge Infrastructure, Weipu database, and Wanfang database was conducted to identify all relevant studies. Odds ratio (OR) with 95% confidence interval (CI) values was applied to evaluate the strength of the association.

Results:

A total of seven studies with 2034 PD cases and 2432 controls were included in the meta-analysis following the inclusion and exclusion criteria. Overall, no significant association between ApaI, BsmI, and TaqI gene polymorphisms and PD susceptibility in all four genetic models was found (T vs. G: OR = 1.00, 95% CI: 0.89–1.12, P = 0.97; A vs. G: OR = 0.94, 95% CI: 0.77–1.15, P = 0.53; C vs. T: OR = 1.03, 95% CI: 0.85–1.25, P = 0.77) while a significant association between FokI (C/T) and PD risk was observed (C vs. T: OR = 1.41, 95% CI: 1.14–1.75, P = 0.001; CC vs. TT: OR = 2.45, 95% CI: 1.52–3.93, P = 0.0002; CT vs. TT: OR = 2.21, 95% CI: 1.38–3.52, P = 0.0009, CC vs. CT+TT: OR = 2.32, 95% CI: 1.49–3.61, P = 0.0002).

Conclusions:

Polymorphisms of ApaI, BsmI, and TaqI may not be associated with the susceptibility to PD while the FokI (C/T) polymorphism is possibly associated with increased PD risk. However, conclusions should be cautiously interpreted due to the relatively small number of studies included.     

Interaction of Polymorphisms of Resistin Gene Promoter -420C/G,Glutathione Peroxidase -1 Gene Pro198Leu and Cigarette Smoking in Nonalcoholic Fatty Liver Disease

Background:

Many studies have suggested that cigarette smoking and polymorphisms of resistin and glutathione peroxidase-1 (GPx-1) genes are closely correlated with the pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, few reports have investigated these associations with respect to NAFLD susceptibility. We, therefore, examined the distribution of polymorphisms in GPx-1 and resistin genes in NAFLD patients and healthy controls and analyzed the relationship between these polymorphisms and smoking status.

Methods:

Nine hundred NAFLD patients and 900 healthy controls were selected, and the genetic polymorphisms of resistin gene promoter-420C/G and GPx-1 gene Pro198Leu were analyzed by polymorphism-polymerase chain reaction (PCR) in DNA extracted from peripheral blood leukocytes. Interactions between the two mutants and the gene–environment interaction with cigarette smoking were also analyzed.

Results:

Genotype frequencies of −420C/G (GG) and Pro198Leu (LL) were significantly higher in NAFLD cases (49.56% and 50.11%, respectively) compared with healthy controls (23.67% and 24.22%, respectively) (P = 0.0069; P = 0.0072). Moreover, the risk of NAFLD with −420C/G (GG) was significantly higher than in controls (odds ratio [OR] =3.1685, 95% confidence interval (CI) =1.9366–5.2073). Individuals carrying Pro198Leu (LL) had a high risk of NAFLD (OR = 3.1424, 95% CI = 1.7951–5.2367). Combined analysis of the polymorphisms showed that the −420C/G (GG)/Pro198Leu (LL) genotype was significantly more common in the NAFLD group than in the control group (39.44% vs. 12.78%, respectively, P = 0.0054), while individuals with −420C/G (GG)/Pro198Leu (LL) had a high risk of NAFLD (OR = 5.0357, 95% CI = 3.1852–7.8106). Moreover, the cigarette smoking rate in the NAFLD group was significantly higher than in the control group (OR = 1.8990, P = 0.0083 in the smoking index (SI) ≤400 subgroup; OR = 5.0937, P = 0.0051 in the SI >400 subgroup), and statistical analysis suggested a positive interaction between cigarette smoking and −420C/G (GG) (γ = 5.6018 in the SI ≤400 subgroup; γ = 4.4770 in the SI >400 subgroup) and Pro198Leu (LL) (γ = 5.7715 in the SI ≤400 subgroup; γ = 4.5985 in the SI >400 subgroup) in increasing the risk of NAFLD.

Conclusion:

NAFLD risk factors include -420C/G (GG), Pro198Leu (LL) and cigarette smoking, and these three factors have a significant additive effect on NAFLD risk.     

Clinical Characteristics and Prognosis of Peri-strut Low-intensity Area Detected by Optical Coherence Tomography

Background:

Peri-strut low-intensity area (PLIA) is a typical image pattern of neointima detected by optical coherence tomography (OCT) after stent implantation. However, few studies evaluated the predictors and prognosis of the PLIA; therefore, we aimed to explore the genesis and prognosis of PLIA detected by OCT in this study.

Methods:

Patients presenting neointimal hyperplasia documented by OCT reexamination after percutaneous coronary intervention were prospectively included from 2009 to 2011. Peri-strut intensity was analyzed and classified into two patterns: Low-intensity and high-intensity. Clinical characteristics were analyzed to assess their contribution to peri-strut intensity patterns. Follow-up were performed in patients who did not receive revascularization during OCT reexamination, and the prognosis of the patients was evaluated.

Results:

There were 128 patients underwent OCT reexamination after stent implantation included in the study. PLIA was detected in 22 (17.2%) patients. The incidence of PLIA was positively correlated with serum triglyceride (odds ratio [OR]: 2.11, 95% confidence interval [CI]: 1.14–3.90, P = 0.017), low-density lipoprotein (OR: 2.61, 95% CI: 1.22–5.66, P = 0.015), history of cerebrovascular disease (OR: 101.11, 95% CI: 6.54–1562.13, P < 0.001), and initial clinical presentation of acute coronary syndrome (ACS, OR: 18.77, 95% CI: 2.73–128.83, P = 0.003) while negatively correlated with stent implantation time (OR: 0.57, 95% CI: 0.33–0.98, P = 0.043). The median follow-up was longer than 3.8 years. Major adverse cardiovascular events (MACEs) occurred in 7 (7.3%) patients while showed no correlation with PLIA. A total of 17 (17.7%) patients experienced unstable angina (UA) and showed significant correlation with PLIA (hazard ratio: 6.16, 95% CI: 1.25–30.33, P = 0.025).

Conclusions:

PLIA detected by OCT was positively correlated with higher serum lipid level, history of cerebrovascular disease and initial presentation of ACS, and negatively correlated with stent implantation time. Patients with PLIA were more likely to have UA than those with high-intensity while no significant difference was found in MACEs.     

Impact of Libido at 2 Weeks after Stroke on Risk of Stroke Recurrence at 1-Year in a Chinese Stroke Cohort Study

Background:

There were few studies on the relation between changes in libido and incidence of stroke recurrence. The aim of this study was to investigate the relationship between libido decrease at 2 weeks after stroke and recurrent stroke at 1-year.

Methods:

It is a multi-centered, prospective cohort study. The 14^th item of the Hamilton Depression Rating Scale-17 was used to evaluate changes of libido in poststroke patients at 2 weeks. Stroke recurrence was defined as an aggravation of former neurological functional deficit, new local or overall symptoms, or stroke diagnosed at re-admission.

Results:

Among 2341 enrolled patients, 1757 patients had completed follow-up data, 533 (30.34%) patients had decreased libido at 2 weeks, and 166 (9.45%) patients had recurrent stroke at 1-year. Multivariate logistic regression analysis showed that, compared with patients with normal libido, the odds ratio (OR) of recurrent stroke in patients with decreased libido was reduced by 41% (OR = 0.59, 95% confidence interval [CI]: 0.40–0.87). The correlation was more prominent among male patients (OR = 0.52, 95% CI: 0.31–0.85) and patients of ≥60 years of age (OR = 0.57, 95% CI: 0.35–0.93).

Conclusions:

One out of three stroke patients in mainland China has decreased libido at 2 weeks after stroke. Decreased libido is a protective factor for stroke recurrence at 1-year, which is more prominent among older male patients.     

Baseline Hepatitis B Virus DNA Level is a Promising Factor for Predicting the 3rd Month Virological Response to Entecavir Therapy: A Study of Strict Defined Hepatitis B virus Induced Cirrhosis

Background:Cirrhosis is a common complication of chronic hepatitis B.It remains unclear if viral and biochemical parameters at baseline affect virological response to entecavir and therefore warrant in...     

Transjugular Intrahepatic Portosystemic Shunt Versus Surgical Shunting in the Management of Portal Hypertension

Background:

The purpose of this article was to clarify the optimal management concerning transjugular intrahepatic portosystemic shunts (TIPSs) and surgical shunting in treating portal hypertension.

Methods:

All databases, including CBM, CNKI, WFPD, Medline, EMBASE, PubMed and Cochrane up to February 2014, were searched for randomized controlled trials (RCTs) comparing TIPS with surgical shunting. Four RCTs, which were extracted by two independent investigators and were evaluated in postoperative complications, mortality, 2- and 5-year survival, hospital stay, operating time and hospitalization charges.

Results:

The morbidity in variceal rehemorrhage was significantly higher in TIPS than in surgical shunts (odds ratio [OR] = 7.45, 95% confidence interval[CI]: (3.93–14.15), P < 0.00001), the same outcomes were seen in shunt stenosis (OR = 20.01, 95% CI: (6.67–59.99), P < 0.000001) and in hepatic encephalopathy (OR = 2.50, 95% CI: (1.63–3.84), P < 0.0001). Significantly better 2-year survival (OR = 0.66; 95% CI: (0.44–0.98), P = 0.04) and 5-year survival (OR = 0.44; 95% CI: (0.30–0.66), P < 0.00001) were seen in patients undergoing surgical shunting compared with TIPS.

Conclusions:

Compared with TIPS, postoperative complications and survival after surgical shunting were superior for patients with portal hypertension. Application of surgical shunting was recommended for patients rather than TIPS.     

Clustering of Risk Behaviors and their Social Determinants among Primary School Learners in Beijing,China: A Cross-sectional Study

Background:

Studies in developed countries reveal that poor lifestyle choices triggering diseases typically cluster among children. However, there is insufficient evidence on the clustering of risk behaviors among children in developing countries. This study aimed to determine the clustering of risk behaviors and their social determinants among 4^th-and 5^th -grade learners in Beijing, China.

Methods:

The sample comprised of 967 learners from six primary schools enrolled migrant and resident learners by two-stage stratified cluster sampling. Prevalence denoted the risk behaviors and their clustering. A log-linear model was used to explore the clustering patterns. Ordinal logistic regression determined the influence of demographic characteristics, school environment, and family context on behavioral clustering.

Results:

The prevalence of none, one, two, and three or more risk factors was 61.2%, 20.0%, 10.8%, and 8.1% for infectious diseases and 46.0%, 30.6%, 15.4%, and 8.0% for chronic diseases, respectively. Some behaviors appeared dependent and were more likely to be observed together. The three most influential factors for infectious diseases were school type (odds ratio [OR] =4.47, 95% confidence interval [CI] 3.00–6.66), school located in an inner suburb (OR = 0.27, 95% CI 0.18–0.38), and gender (OR = 0.56, 95% CI 0.42–0.74). Regarding risk behaviors for chronic diseases, clustering was not associated with household registration status and number of appliances, but was significantly associated with school type (OR = 5.36, 95% CI 3.72–7.73), school located in an inner suburb (OR = 0.59, 95% CI 0.43–0.81), and gender (OR = 0.61, 95% CI 0.47–0.78). School environment variables were the most significant contributor to the number of risk behaviors.

Conclusions:

The characteristics of schools enrolling migrants and residents influenced the number of risk behaviors. Therefore, improved school conditions and integrated behavioral interventions are particularly recommended for health promotion.     

Mitochondrial DNA Haplogroups and the Risk of Sporadic Parkinson's Disease in Han Chinese

Background:

Mitochondrial dysfunction is linked to the pathogenesis of Parkinson''s disease (PD). However, the precise role of mitochondrial DNA (mtDNA) variations is obscure. On the other hand, mtDNA haplogroups have been inconsistently reported to modify the risk of PD among different population. Here, we try to explore the relationship between mtDNA haplogroups and sporadic PD in a Han Chinese population.

Methods:

Nine single-nucleotide polymorphisms, which define the major Asian mtDNA haplogroups (A, B, C, D, F, G), were detected via polymerase chain reaction-restriction fragment length polymorphism or denaturing polyacrylamide gel electrophoresis in 279 sporadic PD patients and 510 matched controls of Han population.

Results:

Overall, the distribution of mtDNA haplogroups did not show any significant differences between patients and controls. However, after stratification by age at onset, the frequency of haplogroup B was significantly lower in patients with early-onset PD (EOPD) compared to the controls (odds ratio [OR] =0.225, 95% confidence interval [CI]: 0.082–0.619, P = 0.004), while other haplogroups did not show significant differences. After stratification by age at examination, among subjects younger than 50 years of age: Haplogroup B also showed a lower frequency in PD cases (OR = 0.146, 95% CI: 0.030–0.715, P = 0.018) while haplogroup D presented a higher risk of PD (OR = 3.579, 95% CI: 1.112–11.523, P = 0.033), other haplogroups also did not show significant differences in the group.

Conclusions:

Our study indicates that haplogroup B might confer a lower risk for EOPD and people younger than 50 years in Han Chinese, while haplogroup D probably lead a higher risk of PD in people younger than 50 years of age. In brief, particular Asian mtDNA haplogroups likely play a role in the pathogenesis of PD among Han Chinese.     

Aggressive Blood Pressure Lowing Therapy in Patients with Acute Intracerebral Hemorrhage is Safe: A Systematic Review and Meta-analysis

Background:

The influence of blood pressure (BP) lowering on intracerebral hemorrhage (ICH) patients is unclear. To assess the safety and efficacy of aggressive antihypertensive therapies in acute ICH patients, we carried out a systematic review and meta-analysis.

Methods:

PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, and VIP database up to July 2014 were searched. High-quality randomized controlled trials were included. Low-quality trials were excluded. Serious adverse events were defined as the primary outcome. The secondary outcomes were hematoma enlargement (HE) at 24 h after onset, mortality, and favorable clinical outcome at 90 days.

Results:

Four high-quality trials involving a total of 1427 patients met the inclusion criteria and were analyzed. Odds ratios (ORs) of primary outcome was 0.96 (95% confidence interval [CI ]: 0.82–1.13, P = 0.61). ORs of HE at 24 h after onset, mortality and favorable clinical outcome at 90 days were 0.91 (95% CI: 0.72–1.17, P = 0.47), 0.97 (95% CI: 0.79–1.20, P = 0.81), 1.13 (95% CI: 0.98–1.30, P = 0.09) respectively.

Conclusions:

Aggressive BP management policies are safe and might have a potency of reducing HE and improving clinical outcome.     

Initiating Characteristics of Early-onset Type 2 Diabetes Mellitus in Chinese Patients

Background:

Type 2 diabetes mellitus (T2DM) has traditionally been considered to affect mainly the elderly; however, the age at diagnosis has gradually reduced in recent years. Although the incidence of young-onset T2DM is increasing, it is still not fully clear the onset characteristics and risk factors of early-onset T2DM. The aim of this study was to describe the initiating characteristics of early-onset T2DM in Chinese patients and evaluate the risk factors for diabetes mellitus.

Methods:

This cross-sectional controlled study was performed using a questionnaire survey method in outpatients of multiple centers in China. A total of 1545 patients with T2DM with an age at onset of <40 years were included, and the control group consisted of subjects aged <40 years with normal blood glucose level.

Results:

In patients with young-onset T2DM, the mean age and initial hemoglobin 1Ac at diagnosis were 32.96 ± 5.40 years and 9.59 ± 2.71%, respectively. Most of the patients were obese, followed irregular diet pattern and sedentary lifestyle, had life or work pressure, and had a family history of diabetes mellitus. Compared with subjects with normal blood glucose level, logistic regression analysis showed that waist-to-hip ratio (odds ratio [OR] 446.99, 95% confidence interval [CI] 42.37–4714.87), family history of diabetes mellitus (OR 23.46, CI 14.47–38.03), dyslipidemia (OR 2.65, CI 1.54–4.56), diastolic blood pressure (OR 1.02, CI 1.00–1.04), and body mass index (OR 0.95, CI 0.92–0.99) are independent factors for early-onset T2DM.

Conclusions:

We observed that abdominal obesity, family history of diabetes mellitus, and medical history of hypertension and dyslipidemia are independent risk factors for early-onset T2DM. It is, therefore, necessary to apply early lifestyle intervention in young people with risk of diabetes mellitus.     

Epidemics of overweight and obesity among growing childhood in China between 1997 and 2009: Impact of Family Income,Dietary Intake,and Physical Activity Dynamics

Background:Obesity has become a major health problem among children and adolescents worldwide.This study aimed to examine the trends of overweight and obesity among childhood in China and assess their ...     

Clinical Characteristics and Risk Factors of Left Ventricular Thrombus after Acute Myocardial Infarction: A Matched Case-control Study

Background:

Left ventricular thrombus (LVT) is reported to be a common complication in acute myocardial infarction (AMI) patients. And it has the potential to cause systemic embolism. This retrospective study was to present the current situation of LVT in clinical practice, as well as to evaluate the clinical characteristics and the risk factors of LVT after AMI.

Methods:

LVT cases (n = 96) were identified from 13,732 AMI (non-ST elevation myocardial infarction was excluded) patients in Fuwai Hospital''s electronic medical records system from January 2003 to January 2013. The controls (n = 192) were gender- and age-matched AMI patients without LVT during this period. A conditional logistic regression (fitted by the Cox model) was performed to identify the independent risk factors.

Results:

The incidence of LVT after AMI was 0.7%. Univariate analysis indicated that the anterior myocardial infarction (especially extensive anterior myocardial infarction), lower left ventricular ejection fraction (LVEF), LVEF ≤40%, severe regional wall motion abnormalities (RWMA), pericardial effusion, and left ventricular aneurysm were all related to LVT after AMI. The independent risk factors obtained from the conditional logistic regression analysis were lower LVEF (odds ratio (OR) = 0.891, 95% confidence interval (CI): 0.828–0.960), extensive anterior myocardial infarction (OR = 6.403, 95% CI: 1.769–23.169), severe RWMA (OR = 7.348, 95% CI: 1.323–40.819), and left ventricular aneurysm (OR = 6.955, 95% CI: 1.673–28.921).

Conclusions:

This study indicated that lower LVEF, extensive anterior myocardial infarction, severe RWMA, and left ventricular aneurysm were independent risk factors of LVT after AMI. It also suggested that further efforts are needed for the LVT diagnosis after AMI in clinical practice.     

Clinical and Angiographic Predictors of Major Side Branch Occlusion after Main Vessel Stenting in Coronary Bifurcation Lesions

Background:

Major side branch (SB) occlusion is one of the most serious complications during percutaneous coronary intervention (PCI) for bifurcation lesions. We aimed to characterize the incidence and predictors of major SB occlusion during coronary bifurcation intervention.

Methods:

We selected consecutive patients undergoing PCI (using one stent or provisional two stent strategy) for bifurcation lesions with major SB. All clinical characteristics, coronary angiography findings, PCI procedural factors and quantitative coronary angiographic analysis data were collected. Multivariate logistic regression analysis was performed to identify independent predictors of SB occlusion. SB occlusion after main vessel (MV) stenting was defined as no blood flow or any thrombolysis in myocardial infarction (TIMI) flow grade decrease in SB after MV stenting.

Results:

Among all 652 bifurcation lesions, 32 (4.91%) SBs occluded. No blood flow occurred in 18 lesions and TIMI flow grade decreasing occurred in 14 lesions. In multivariate analysis, diameter ratio between MV/SB (odds ratio [OR]: 7.71, 95% confidence interval [CI]: 1.53–38.85, P = 0.01), bifurcation angle (OR: 1.03, 95% CI: 1.02–1.05, P < 0.01), diameter stenosis of SB before MV stenting (OR: 1.05, 95% CI: 1.03–1.07, P < 0.01), TIMI flow grade of SB before MV stenting (OR: 3.59, 95% CI: 1.48–8.72, P < 0.01) and left ventricular eject fraction (LVEF) (OR: 1.06, 95% CI: 1.02–1.11, P < 0.01) were independent predictors of SB occlusion.

Conclusions:

Among clinical and angiographic findings, diameter ratio between MV/SB, bifurcation angle, diameter stenosis of SB before MV stenting, TIMI flow grade of SB before MV stenting and LVEF were predictive of major SB occlusion after MV stenting.     

Positive Association Between Type 2 Diabetes Risk Alleles Near CDKAL1 and Reduced Birthweight in Chinese Han Individuals

Background:Fetal insulin hypothesis was proposed that the association between low birth weight and type 2 diabetes is principally genetically mediated.The aim of this study was to investigate whether c...     

Association of Estrogen Receptor Gene Polymorphisms and Primary Biliary Cirrhosis in a Chinese Population: A Case–Control Study

Background:

Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease characterized by destruction of the interlobular bile ducts and a striking female predominance. The aim of this study was to identify associations between estrogen receptor (ESR) gene polymorphisms with the risk of developing PBC and abnormal serum liver tests in a Chinese population.

Methods:

Thirty-six patients with PBC (case group) and 35 healthy individuals (control group) from the First Hospital of Jilin University were studied. Whole genomic DNA was extracted from all the participants. Three single-nucleotide polymorphisms (rs2234693, rs2228480, and rs3798577) from ESR1 and two (rs1256030 and rs1048315) from ESR2 were analyzed by a pyrosequencing method. Demographic data and liver biochemical data were collected.

Results:

Subjects with the T allele at ESR2 rs1256030 had 1.5 times higher risk of developing PBC than those with the C allele (odds ratio [OR] = 2.1277, 95% confidence interval [CI] = 1.1872–4.5517). Haplotypes TGC of ESR1 rs2234693, rs2228480, and rs3798577 were risk factors for having PBC. The C allele at ESR1 rs2234693 was associated with abnormal alkaline phosphatase (OR = 5.2469, 95% CI = 1.3704–20.0895) and gamma-glutamyl transferase (OR = 3.4286, 95% CI = 1.0083–13.6578) levels in PBC patients.

Conclusions:

ESR2 rs1256030 T allele may be a significant risk factor for the development of PBC. Screening for patients with gene polymorphisms may help to make early diagnoses in patients with PBC.     

Efficacy and Safety of OnabotulinumtoxinA in Treating Neurogenic Detrusor Overactivity: A Systematic Review and Meta-analysis

Background:

OnabotulinumtoxinA is widely used in treating neurogenic detrusor overactivity (NDO). We carried out a systematic review and meta-analysis to assess the efficacy and safety of the drug for treating NDO.

Methods:

We searched the following databases: Medline, EMBASE, and the Cochrane Controlled Trials Register. All published randomized double-blind, placebo-controlled trials of onabotulinumtoxinA for the treatment of NDO were identified in the analysis. The reference lists of the retrieved studies were also investigated.

Results:

Four publications involving a total of 807 patients were identified in the analysis, which compared onabotulinumtoxinA with placebo. The changes of the mean number of urinary incontinence per week (the standardized mean difference [SMD] = −10.91, 95% confidence intervals [CIs] = −14.18–−7.63, P < 0.0001); maximum cystometric capacity (SMD = 146.09, 95% CI = 126.19–165.99, P < 0.0001) and maximum detrusor pressure (SMD = −32.65, 95% CI = −37.83–−27.48, P < 0.0001) indicated that onabotulinumtoxinA was more effective than the placebo, despite the doses of onabotulinumtoxinA. Safety assessments primarily localized to the urinary tract indicated onabotulinumtoxinA were often associated with more complications. Urinary tract infections (relative risk [RR] =1.48, 95% CI = 1.20–1.81, P = 0.0002); hematuria (RR = 1.81, 95% CI = 1.00–3.24, P = 0.05) and urinary retention (RR = 5.87, 95% CI = 3.61–9.56, P < 0.0001).

Conclusions:

This meta-analysis indicates that onabotulinumtoxinA to be an effective treatment for NDO with side effects primarily localized to urinary tract.     

Thalidomide-based Regimens for Elderly and/or Transplant Ineligible Patients with Multiple Myeloma: A Meta-analysis

Background:

Thalidomide is an immunomodulatory and anti-angiogenic drug that has shown promise in patients with myeloma. Trials comparing efficacy of standard melphalan and prednisone (MP) therapy with MP plus thalidomide (MPT) in transplant-ineligible or elderly patients with multiple myeloma (MM) have provided conflicting evidence. This meta-analysis aimed to determine the efficacy and toxicity of thalidomide in previously untreated elderly patients with myeloma.

Methods:

Medline, the Cochrane Controlled Trials register, conference proceedings of the American Society of Hematology (1995–2014), the American Society of Clinical Oncology (1995–2014), and CBM, VIP, and CNKI databases were searched for randomized control trials with the use of the medical subject headings “MM” and “thalidomide”. Trials were assessed by two reviewers for eligibility. Meta-analysis was conducted using a fixed effects model. Sensitivity analysis was performed to test the robustness of the findings.

Results:

Overall, seven trials were identified, covering a total of 1821 subjects. The summary hazard ratio (thalidomide vs. control) was 0.82 (95% confidence interval [CI]: 0.72–0.94) for overall survival (OS), and 0.65 (95% CI: 0.58–0.73) for progression-free survival, in favor of thalidomide treated group. The risk ratio of complete response with induction thalidomide was 3.48 (95% CI: 2.24–5.41). A higher rate of III/IV adverse events were observed in MPT arm compared with the MP arm. However, analysis of sub-groups administering anticoagulation as venous thromboembolism prophylaxis suggested no difference in relative risk of thrombotic events between two arms (RR = 1.47, 95% CI: 0.43–5.07, P = 0.54). Further analysis of trials on the treatment effects of MPT versus MP on adverse events-related mortality showed no statistical difference between two arms (RR = 1.24, 95% CI: [0.95–1.63], P = 0.120).

Conclusion:

Thalidomide appears to improve the OS of elderly and/or transplant-ineligible patients with MM when it is added to standard MP therapy.     

Comparison of Therapeutic Efficacy between Gastrectomy with Transarterial Chemoembolization Plus Systemic Chemotherapy and Systemic Chemotherapy Alone in Gastric Cancer with Synchronous Liver Metastasis

Background:

Systemic chemotherapy (SC) is the recommended treatment for gastric cancer with liver metastasis. However, the improvement in survival has been disappointing. The aim of this study was to compare the therapeutic efficacy of gastrectomy with transarterial chemoembolization plus SC (GTC) and SC alone for gastric cancer with synchronous liver metastasis.

Methods:

From January 2008 to December 2013, 107 gastric cancer patients with synchronous liver metastasis attending the four participating centers were enrolled in this multicenter, ambispective, controlled cohort study. Patients who underwent GTC (n = 32) were compared with controls who were received SC alone (n = 75). The primary endpoints of the study were overall survival (OS) and progression-free survival (PFS). The secondary endpoints were response rate to treatment and treatment-related adverse effects.

Results:

The median OS was 14.0 months (95% confidence interval [CI]: 13.1–14.9 months) in the GTC treatment group and 8.0 months (95% CI: 6.6–9.4 months) in SC group, this difference being statistically significant (P < 0.001). The median PFS was significantly longer in the GTC than in the SC group (5 months, 95% CI: 2.2–7.8 months vs. 3 months, 95% CI: 2.3–3.4 months, respectively) (P < 0.001). The rate of response to treatment was significantly better in the GTC than the SC group (59.4% vs. 37.4%, respectively) (P = 0.035). According to multivariate analysis, OS in patients receiving combination treatment was significantly correlated with the size (P = 0.037) and extent of liver metastases (P < 0.001). PFS was also correlated with the extent of liver metastases (P = 0.003).

Conclusions:

GTC is more effective than SC alone in patients with gastric cancer with synchronous liver metastasis. GTC therapy prolongs the survival of selected gastric cancer patients with synchronous liver metastasis.