Apolipoprotein E polymorphism and the risk of aneurysmal subarachnoid hemorrhage in a South Indian population

Background

The rupture of a brain aneurysm causes bleeding in the subarachnoid space. This is known as aneurysmal subarachnoid hemorrhage (aSAH). We evaluated the association of apolipoprotein E (APOE) polymorphism and the risk of aSAH in a South Indian population.

Methods

The study was performed on 200 subjects with aSAH and 253 healthy control subjects. Blood samples (5 ml) were used to isolate DNA and genotyping was performed for rs7412 and rs429358 using a Taqman allelic discrimination assay. Statistical software R.3.0.11 was used to statistically analyze the data and a p value <?0.05 was considered as statistically significant.

Results

We found a significant association with the risk of aSAH in ε3/ ε4 genetic model (OR?=?1.91, 95% CI?=?1.16–3.14, p?=?0.01). However, in the other genetic models and allele frequency, there was no significant association with the risk of aSAH. In subtyping, we found a significant association of ε2 allele frequency with posterior communicating artery (PCOM) aneurysm (OR?=?3.59, 95% CI?=?1.11–11.64, p?=?0.03).

Conclusion

Our results suggest that APOE polymorphism has an influence on the risk of aSAH in this South Indian population, specifically in the PCOM subtype.

     

Association between <Emphasis Type="Italic">TNF,IL1B,IL6, IL10</Emphasis> and <Emphasis Type="Italic">IFNG</Emphasis> polymorphisms and recurrent miscarriage: a case control study

Background

Approximately half of recurrent miscarriages have unexplained etiology. Recent evidences suggest that cytokines are important determinants in pregnancy maintenance and as such, cytokine gene polymorphisms, which can affect cytokine production and/or functionality, could play a role in the disorder. Thus, we aimed to investigate the association of selected cytokine gene polymorphisms with risk of recurrent miscarriage among Chinese.

Methods

TNF -238G > A, TNF -308G > A, IL1B -511 T > C, IL1B 3954C > T, IL6 -174G > C, IL6 -634C > G, IL10 -1082A > G and IFNG 874A > T polymorphisms were genotyped on 775 women with idiopathic recurrent miscarriage and 805 healthy parous control women. Logistic regression analysis was performed to determine the odds ratios (ORs) of the association between the polymorphisms and recurrent miscarriage risk.

Results

Among the eight polymorphisms studied, only the IL1B -511 T > C and IL6 -634C > G polymorphisms showed statistically significant associations with recurrent miscarriage risk. For the former, a significantly increased risk of recurrent miscarriage was observed for the mutant (CC) genotype (OR: 1.377; 95% CI: 1.039–1.824; P?=?0.026). However, for the IL6 -634C?>?G polymorphism, a decreased recurrent miscarriage risk was observed for the heterozygous (CG) genotype (OR: 0.614; 95% CI: 0.493–0.765; P < 0.001) and the mutant (GG) genotype (OR: 0.414; 95% CI: 0.251–0.684; P?=?0.001).

Conclusions

The IL1B -511 T > C polymorphism may serve as important risk factor for recurrent miscarriage while the IL6 -634C > G polymorphism may protect against the risk of recurrent miscarriage.

     

In-hospital cardiovascular events after liver transplantation: predictors and long-term outcome

Introduction

Liver transplantation has emerged as a successful therapy for end-stage liver disease. However, cardiovascular mortality is the leading cause of fatality in the postoperative period. The aim of this study was to reveal the prevalence and identify risk factors of early cardiovascular events (CVEs).

Methods

We performed a retrospective study of all consecutive patients who underwent a primary liver transplantation from 1986 to 2017 (n?=?916). We investigated the occurrence of in-hospital CVEs, their predictors, and short- and long-term outcome.

Results

The prevalence of CVEs was 11%. The adjusted analysis showed that higher age (OR 1.06, 95% CI 1.03–1.09), higher MELD score (OR 1.04, 95% CI 1.01–1.07 CI) and sinus tachycardia at time of screening (OR 3.12, 95% CI 1.45–6.72) were positive predictors for a CVE. Preoperative propranolol use showed a trend towards a higher risk of CVE (OR 1.66, 95% CI 1.00–2.77, p?=?0.051). In a sub-analysis of patients where echocardiography data were available (n?=?597), a larger left atrial diameter and a higher E/E′ ratio were related to early CVEs. Ten-year survival in 30-day survivors was favourable (68.6%; 56.0% vs. 69.8% in the CVE+ vs. the CVE-group, respectively, p?=?0.056).

Discussion

In conclusion, besides known risk factors (age and MELD score), sinus tachycardia (related to the presence of acute liver failure and cirrhosis) was an independent predictor for CVE after liver transplantation.

     

Urine metabolites are associated with glomerular lesions in type 2 diabetes

Introduction

Little is known about the association of urine metabolites with structural lesions in persons with diabetes.

Objectives

We examined the relationship between 12 urine metabolites and kidney structure in American Indians with type 2 diabetes.

Methods

Data were from a 6-year clinical trial that assessed renoprotective efficacy of losartan, and included a kidney biopsy at the end of the treatment period. Metabolites were measured in urine samples collected within a median of 6.5 months before the research biopsy. Associations of the creatinine-adjusted urine metabolites with kidney structural variables were examined by Pearson’s correlations and multivariable linear regression after adjustment for age, sex, diabetes duration, hemoglobin A_1c, mean arterial pressure, glomerular filtration rate (iothalamate), and losartan treatment.

Results

Participants (n?=?62, mean age 45?±?10 years) had mean?±?standard deviation glomerular filtration rate of 137?±?50 ml/min and median (interquartile range) urine albumin:creatinine ratio of 34 (14–85) mg/g near the time of the biopsy. Urine aconitic and glycolic acids correlated positively with glomerular filtration surface density (partial r?=?0.29, P?=?0.030 and r?=?0.50, P?<?0.001) and total filtration surface per glomerulus (partial r?=?0.32, P?=?0.019 and r?=?0.43, P?=?0.001). 2-ethyl 3-OH propionate correlated positively with the percentage of fenestrated endothelium (partial r?=?0.32, P?=?0.019). Citric acid correlated negatively with mesangial fractional volume (partial r=-0.36, P?=?0.007), and homovanillic acid correlated negatively with podocyte foot process width (partial r=-0.31, P?=?0.022).

Conclusions

Alterations of urine metabolites may associate with early glomerular lesions in diabetic kidney disease.

     

Effects of <Emphasis Type="Italic">ADIPOQ</Emphasis> polymorphisms on PCOS risk: a meta-analysis

Background

Whether adiponectin (ADIPOQ) polymorphisms are associated with the risk of polycystic ovary syndrome (PCOS) remain controversial. Therefore, we performed this study to better explore correlations between ADIPOQ polymorphisms and PCOS risk.

Methods

Literature retrieve was conducted in PubMed, Medline and Embase. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.

Results

Eighteen studies were enrolled for analyses. Pooled overall analyses showed that rs1501299 polymorphism was significantly associated with PCOS risk (recessive model: p?=?0.02, OR?=?0.77, 95%CI 0.62–0.95; allele model: p?=?0.001, OR?=?1.15, 95%CI 1.06–1.26). Further subgroup analyses according to ethnicity of participants revealed that rs1501299 and rs2241766 polymorphisms were both significantly correlated with PCOS risk in Caucasians. In addition, rs1501299 polymorphism was also significantly correlated with PCOS risk in East Asians.

Conclusions

Our findings indicated that rs1501299 and rs2241766 polymorphisms might serve as genetic biomarkers of PCOS in certain ethnicities.

     

Gel electrophoresis of human sperm: a simple method for evaluating sperm protein quality

Background

The limitations of conventional sperm analyses have highlighted the need for additional means of evaluating sperm quality.

Methods

In a study of a cohort of 245 men with known conventional sperm parameters, one-dimensional PAGE was used to monitor protein content and quality in samples from individual ejaculates.

Results

The sperm protein content varied markedly from sample to another, especially in the high-molecular-weight range. The intensity of the 80–110 kDa bands was correlated with progressive motility (r?=?0.15, p?=?0.015) and was significantly higher (p?=?0.0367) in the group of men with conventional parameters above the World Health Organization’s 2010 reference values than in the group with at least one subnormal parameter (i.e. semen volume, sperm concentration, sperm count per ejaculate, progressive motility, proportion of normal forms or multiple anomaly index below the lower reference value). Using mass spectrometry, the 80–110 kDa bands were found to correspond primarily to three proteins from the flagellum’s fibrous sheath: A-kinase anchor protein 4, A-kinase anchor protein 3, and spermatogenic cell-specific type 1 hexokinase.

Conclusion

One-dimensional PAGE constitutes a simple, rapid, reliable, inexpensive method for analyzing proteins associated with sperm motility in individual human ejaculates.

     

Candidemia in Adults at a Tertiary Hospital in China: Clinical Characteristics,Species Distribution,Resistance, and Outcomes

Background

Candidemia is one of the most common nosocomial bloodstream infections. Early diagnosis and antifungal treatment improve clinical outcomes in some studies but not all, with diverse data reported from different institutions. Similarly, antifungal resistance is more common in the USA than in Europe, but there is little data regarding the microbiology and clinical course of candidemia in adult patients in Asia.

Aims

(1) To capture species distribution and drug resistance rates among Candida bloodstream isolates, (2) to describe clinical features of candidemia, and (3) to identify factors associated with all-cause mortality, with emphasis on early initiation of antifungal treatment, at a large tertiary University Hospital in China.

Methods

In this single-center retrospective study, we identified all patients with candidemia, between 2008 and 2014. Demographic and clinical characteristics, microbiological information, details of antifungal therapy and clinical outcomes were collected.

Results

We studied 166 patients. 71 (42.8%) had cancer. Candida albicans was the most frequent species (37.3%), followed by C. parapsilosis (24.1%), C. tropicalis (22.8%), and C. glabrata (14.5%). Antifungal resistance was more frequent in non-albicans strains and especially C. glabrata. Twenty patients received inappropriate treatment with all-cause mortality of 35%. The remaining 146 patients had significantly lower mortality (21.9%, P?=?0.045). Among patients who received antifungal treatment, mortality rate increased with time to appropriate antifungal therapy (AAT): 13.7%, for?<?24 h, 21.1% for 24–48 h, 23.1% for?>?48 h, and 32.4% among patients who received no AT (χ² for trend P?=?0.039). Initiating AAT more than 24 h after blood culture collection was an independent risk factor for mortality, after adjustment for other confounders (OR 7.1, 95% CI 1.3–39.4, P?=?0.024).

Conclusions

Candida albicans was the most frequent cause of candidemia at a large tertiary hospital in China, but antifungal resistance is a growing concern among non-albicans Candida species. The mortality rate of patients treated with ineffective antifungal agents based on in vitro susceptibilities was similar to that of patients who received no treatment at all, and delayed initiation of antifungal treatment was associated with increased risk of death.

     

The relationship between human leukocyte antigen-DP/DQ gene polymorphisms and the outcomes of HCV infection in a Chinese population

Background

Recently, human leukocyte antigen (HLA) class-II gene polymorphisms have been reported to be related to Hepatitis C virus (HCV) infection and chronicity. The objective of this study was to explore the relationship of HLA-DP rs9277535 and HLA-DQ rs7453920 with the outcomes of HCV infection.

Methods

The rs9277535 and rs7453920 were genotyped in 370 subjects with chronic HCV infection, 194 subjects with spontaneous HCV clearance, and 973 subjects with non-HCV infection from the Chinese population using the ABI TaqMan allelic discrimination assay.

Results

Logistic regression analyses showed that the minor allele A of rs7453920 significantly increased the susceptibility of HCV infection in dominant model (adjusted OR?=?1.33, 95% CI: 1.04–1.71, P?=?0.026) and additive models (adjusted OR?=?1.30, 95% CI: 1.06–1.60, P?=?0.012). Rs9277535 A allele significantly increased the risk of chronic HCV infection in dominant model (adjusted OR?=?1.52, 95% CI: 1.01–2.28, P?=?0.046). Haplotype AA showed a higher risk of HCV infection than the most frequent haplotype GG (adjusted OR?=?1.37, 95% CI: 1.05–1.78, P?=?0.018).

Conclusion

The HLA-DQ rs7453920 and -DP rs9277535 mutations were significantly associated with HCV infection susceptibility and chronicity, respectively.

     

Pediatric premedication: a double-blind randomized trial of dexmedetomidine or ketamine alone versus a combination of dexmedetomidine and ketamine

Background

Preoperative anxiety is common in pediatric patients. When dexmedetomidine is used alone for sedation as premedication, children tend to awaken when separated from their parents, and body movements occur during invasive procedures. We tested the hypothesis that the combination of dexmedetomidine and ketamine may be a useful premedication to alleviate preoperative anxiety and improve cooperation during intravenous cannulation in pediatric patients, while producing minimal adverse events.

Methods

A total of 135 children, aged 2–5 years and American Society of Anesthesiologists status I–II, scheduled for eye surgery were randomly allocated to receive intranasal dexmedetomidine 2.5 μg/kg (group D), oral ketamine 3 mg/kg and intranasal dexmedetomidine 2 μg/kg (group DK), or oral ketamine 6 mg/kg (group K) 30 min before surgery. Sedation state was evaluated every 10 min after premedication and emotional state was assessed during separation from their parents and peripheral intravenous cannulation. Adverse events were recorded for 24 h postoperatively. The primary endpoint was the rate of successful intravenous cannulation.

Results

The rate of successful venous cannulation was 47% with dexmedetomidine alone, 68% with ketamine alone, and 80% with combined premedication (P?=?0.006). The rate of satisfactory separation from parents was not different among groups. The incidence of adverse events was higher in group K compared with the other two groups (postoperative vomiting, P?=?0.0041; respiratory-related complications during the perioperative period, P?=?0.0032; and postoperative psychological/psychiatric adverse events, P?=?0.0152).

Conclusion

The combination of intranasal dexmedetomidine 2 μg/kg and oral ketamine 3 mg/kg produces satisfactory separation from parents and more successful venous cannulation, allowing children to smoothly accept induction of general anesthesia.

Trial registration

Chinese Clinical Trial Register (Unique identifier: ChiCTR-TRC-14004475, Date of registration: 2 April 2014).

     

Characterization of a <Emphasis Type="Italic">Bacillus amyloliquefaciens</Emphasis> strain for reduction of citrulline accumulation during soy sauce fermentation

Objectives

To reduce the amount of citrulline produced by arginine-consuming bacteria in the moromi mash during soy sauce production.

Results

Bacillus amyloliquefaciens JY06, a salt-tolerant strain with high arginine consumption ability and low citrulline accumulation capacity, was isolated from moromi mash. The concentration of citrulline was decreased from 26.8 to 5.1 mM and ethyl carbamate in soy sauce, after sterilization, decreased from 97 to 17 μg kg^?1 when B. amyloliquefaciens JY06 was added during fermentation. The aroma of the sauce was improved by increasing the ester content.

Conclusions

B. amyloliquefaciens JY06 is a beneficial bacterium that can be used in soy sauce fermentation to eliminate ethyl carbonate and enhance the flavor of the sauce.

     

Statin consumption as a risk factor for developing colorectal cancer: a retrospective case study

Background

Statins are the backbone of lipid-lowering therapy and are among the most commonly prescribed drugs in the elderly population in Sweden today. Colorectal cancer is the second most common cancer in men and women, after prostate and breast cancer, respectively, with a median age of 72 years at diagnosis. Statins induce mitochondrial damage leading to accumulation of reactive oxygen species in the cell. Reactive oxygen species can cause mutations in mitochondrial as well as nuclear DNA leading to the development of cancer. Our hypothesis was that statins increase the risk for colorectal cancer.

Methods

A case study was performed on consecutive cases of colorectal cancer diagnosed at Norrlands University Hospital (NUS) in Umeå between 2012 and 2015 (n?=?325). Patients diagnosed with diabetes mellitus type II (DM II n?=?65) were excluded in the primary endpoint analysis (occurrence of colorectal cancer). As control, three databases were used to create an age-matched population in order to calculate the proportion of inhabitants using statins in the county of Västerbotten, Sweden. A secondary endpoint was cancer-specific survival among our study group of colorectal cancer patients, including those with DM II, investigating whether there was a difference if the patient was a ‘recent’ statin user or not at the time of diagnosis.

Results

Statin use at the time of colorectal cancer diagnosis in the study group was 23.8%. The corresponding figure in an age-matched population in Västerbotten was 24.6%. Using a one-proportional one-sided z test, there was no significant difference between these (23.8%, 95% CI 18.6–29.0%, p?=?0.601). When comparing groups 20–64 years of age, the difference was greater with recent statin use in 17.8% in the study population and 11.9% in Västerbotten (17.8%, 95% CI 9.0–26.6%, p?=?0.059). When considering cancer-specific survival, no significant difference in survival was seen when comparing ‘former/never’ statin users as reference category with ‘recent’ users diagnosed with colorectal cancer (HR 1.39, 95% CI 0.89–2.16).

Conclusions

No significant increase in risk for developing colorectal cancer among patients (type II diabetics excluded) medicated with statins was found. We found no correlation between ‘recent’ statin use at the time of diagnosis and cancer-specific survival.

     

Device updates successfully reduce T‑wave oversensing and inappropriate shocks in subcutaneous ICD patients

Aims

To analyse the impact of device and software updates on the prevention of T?wave oversensing (TWOS) and inappropriate shocks (IS) in subcutaneous ICD (S-ICD) patients.

Background

TWOS is a feared complication after implantation. It may lead to harmful IS. To date, specific strategies to reduce these events are lacking.

Methods

In this retrospective single-centre trial we analysed 146 S?ICD patients who were implanted between 2010 and 2016. In all eligible consecutive patients (n?=?139), follow-up of at least 6 weeks was studied. The incidence of TWOS/IS was analysed in patients receiving a 2^nd generation S?ICD (Emblem-S-ICD) between 2014 and 2016 (Emblem). Their outcome was compared with a control group (SQ) treated with the SQ1010 device between 2010 and 2014, who were followed up for a maximum of 2 years. Furthermore, to test if the software update SMR8 reduces inappropriate shocks in the SQ1010-S-ICD population, the incidence of TWOS/IS was evaluated before and after update installation.

Results

Basic characteristics and indications for S?ICD implantation were similar in both groups. However, the cumulative incidence of TWOS/IS was significantly decreased in Emblem vs. SQ (SQ: 15.4%, n?=?14/91 vs. Emblem 4.2%, n?=?2/48; p?=?0.049). Furthermore, with regards to the SQ population we also observed a trend towards a significant reduction of TWOS/IS after installation of the software update SMR8 in 2014 (before update: 13.4%, n?=?11/82 vs. after update: 4.6%, 3/65, p?=?0.07).

Conclusion

2^nd generation devices but probably also the SMR8 software update reduce the incidence of TWOS/IS in S?ICD patients.

     

Association analysis of ILVBL gene polymorphisms with aspirin-exacerbated respiratory disease in asthma

Background

We previously reported that the ILVBL gene on chromosome 19p13.1 was associated with the risk for aspirin-exacerbated respiratory disease (AERD) and the percent decline of forced expired volume in one second (FEV1) after an oral aspirin challenge test. In this study, we confirmed the association between polymorphisms and haplotypes of the ILVBL gene and the risk for AERD and its phenotype.

Methods

We recruited 141 AERD and 995 aspirin-tolerant asthmatic (ATA) subjects. All study subjects underwent an oral aspirin challenge (OAC). Nine single nucleotide polymorphisms (SNPs) with minor allele frequencies above 0.05, which were present in the region from 2 kb upstream to 0.5 kb downstream of ILVBL in Asian populations, were selected and genotyped.

Results

In an allelic association analysis, seven of nine SNPs were significantly associated with the risk for AERD after correction for multiple comparisons. In a codominant model, the five SNPs making up block2 (rs2240299, rs7507755, rs1468198, rs2074261, and rs13301) showed significant associations with the risk for AERD (corrected P?=?0.001–0.004, OR?=?0.59–0.64). Rs1468198 was also significantly associated with the percent decline in FEV1 in OAC tests after correction for multiple comparisons in the codominant model (corrected P?=?0.033), but the other four SNPs in hapblock2 were not.

Conclusion

To the best of our knowledge, this is the first report of an association between SNPs on ILVBL and AERD. SNPs on ILVBL could be promising genetic markers of this condition.

     

Short versus long duration of dual antiplatelet therapy following drug-eluting stents: a meta-analysis of randomised trials

Background

Dual antiplatelet therapy (DAPT) remains the cornerstone therapy in the prevention of ischaemic events following drug-eluting stent (DES) implantation. Mandatory duration of DAPT after DES however, is a matter of debate. We aimed to evaluate safety and efficacy of short-term (up to 6 months) versus long-term (12 months) DAPT after DES implantation.

Methods

We searched PubMed, EMBASE, Cochrane databases, and international meetings for randomised clinical trials (RCTs) comparing short with long DAPT. We performed a systematic review and meta-analysis of major trials with primary outcomes: all-cause death, myocardial infarction, definite or probable stent thrombosis, stroke, and major bleeding event.

Results

Nine RCTs with a total number of 19,099 patients were pooled in the present meta-analysis. When compared with long DAPT, short DAPT was associated with a significant reduction in major bleeding events (0.62% vs. 1.10%, risk ratio (RR) 0.58, 95% confidence interval (CI) 0.39 to 0.86, p?<?0.007, I²?=?21%), whereas all-cause death (1.65% vs. 1.84%, RR 0.90, 95% CI 0.73 to 1.11, p?=?0.34, I2?=?0%), myocardial infarction (1.91% vs. 1.68%, RR 1.14, 95% CI 0.92 to 1.40, p?=?0.23, I2?=?0%), definite or probable stent thrombosis (0.62% vs. 0.47%, RR 1.25, 95% CI 0.84 to 1.86, p?=?0.27, I2?=?0%), and stroke (0.60% vs. 0.67%, RR 0.91, 95% CI 0.63 to 1.31, p?=?0.61, I2?=?0%) were similar.

Conclusions

Short DAPT following DES implantation results in a significant reduction of major bleeding events with no apparent increase in all-cause death, myocardial infarction, stent thrombosis, or stroke. Future dedicated trials should investigate the optimal strategies for patient-tailored DAPT in various subgroups.

     

Serum vaspin concentration in elderly patients with type 2 diabetes mellitus and macrovascular complications

Background

Adipose tissue, an endocrine organ of the body, is involved in some obesity-related disease states such as insulin resistance, diabetes mellitus, and atherosclerosis. Vaspin is a novel adipocyte with insulin sensitizing effects. In this study, we planned to estimate serum vaspin concentrations as related to glycemic status and the presence of macrovascular complications among elderly patients with type-2 diabetes mellitus (T2DM).

Methods

A total of 230 elderly patients with T2DM were evaluated. These patients were divided into two groups: patients without complications (T2DM group, n?=?110), and patients with macrovascular complications (T2DM + MC group, n?=?120). In addition, 60 healthy elderly subjects were enrolled and assigned into the control group (NC group). Relevant parameters were matched for age and gender ratio. Serum vaspin concentrations were measured by Enzyme-linked immunosorbent assay (ELISA). Anthropometric measurements, plasma glucose and HbA_1C levels, insulin concentration, liver and kidney functions, and lipid profile were measured for each participant.

Results

Serum vaspin concentrations were significantly higher in the T2DM group than in the T2DM + MC group (F?=?13.122, P?<?0.01). These concentrations were also significantly higher among females, compared to males (T?=?3.567, P?<?0.05). Logistic regression analysis revealed that serum vaspin concentration, systolic blood pressure, HDL-C and T2DM duration were independent influencing factors for diabetic macrovascular complications.

Conclusion

Serum vaspin may be considered as a potential marker to assess the status of elderly patients with T2DM and the risk of developing serious macrovascular complications. Further prospective studies are warranted.

Trial registration

ChiCTR-OPC-14005698, retrospectively registered on 20 Dec. 2014.

     

Trends in patient characteristics and clinical outcome over 8 years of transcatheter aortic valve implantation

Aim

In the evolving field of transcatheter aortic valve implantations (TAVI) we aimed to gain insight into trends in patient and procedural characteristics as well as clinical outcome over an 8?year period in a real-world TAVI population.

Methods

We performed a single-centre retrospective analysis of 1,011 consecutive patients in a prospectively acquired database. We divided the cohort into tertiles of 337 patients; first interval: January 2009–March 2013, second interval: March 2013–March 2015, third interval: March 2015–October 2016.

Results

Over time, a clear shift in patient selection was noticeable towards lower surgical risks including Society of Thoracic Surgeons predicted risk of mortality score and comorbidity. The frequency of transfemoral TAVI increased (from 66.5 to 77.4%, p?=?0.0015). Device success improved (from 62.0 to 91.5%, p?<?0.0001) as did the frequency of symptomatic relief (≥1 New York Heart Association class difference) (from 73.8 to 87.1%, p?=?0.00025). Complication rates decreased, including in-hospital stroke (from 5.0 to 2.1%, p?=?0.033) and pacemaker implantations (from 10.1 to 5.9%, p?=?0.033). Thirty-day mortality decreased (from 11.0 to 2.4%, p?<?0.0001); after adjustment for patient characteristics, a mortality-risk reduction of 72% was observed (adjusted hazard ratio [HR]: 0.28, 95% confidence interval [CI]: 0.13–0.62). One-year mortality rates decreased (from 23.4 to 11.4%), but this was no longer significant after a landmark point was set at 30 days (mortality from 31 days until 1 year) (adjusted HR: 0.69, 95% CI: 0.41–1.16, p?=?0.16).

Conclusion

A clear shift towards a lower-risk TAVI population and improved clinical outcome was observed over an 8?year period. Survival after TAVI improved impressively, mainly as a consequence of decreased 30-day mortality.

     

MYO18B promotes hepatocellular carcinoma progression by activating PI3K/AKT/mTOR signaling pathway

Background

MYO18B has been identified as a novel tumor suppressor gene in several cancers. However, its specific roles in the progression of hepatocellular carcinoma (HCC) has not been well defined.

Methods

We firstly identified the expression and prognostic values of MYO18B in HCC using TCGA cohort and our clinical data. Then, MYO18B knockdown by RNA inference was implemented to investigate the effects of MYO18B on HCC cells. Quantitative RT-PCR and Western blot were used to determine gene and protein expression levels. CCK-8 and colony formation assays were performed to examine cell proliferation capacity. Wound healing and transwell assays were used to evaluate the migration and invasion of HepG2 cells.

Results

MYO18B was overexpressed and correlated with poor prognosis in HCC. MYO18B expression was an independent risk factor for overall survival. Knockdown of MYO18B significantly inhibited the proliferation, migration and invasion of HepG2 cells. Meanwhile, MYO18B knockdown could effectively suppress the phosphorylation of PI3K, AKT, mTOR and P70S6K, suggesting that MYO18B might promote HCC progression by targeting PI3K/AKT/mTOR signaling pathway.

Conclusions

MYO18B promoted tumor growth and migration via the activation of PI3K/AKT/mTOR signaling pathway. MYO18B might be a promising target for clinical intervention of HCC.

     

Long-term follow-up in adults after tetralogy of Fallot repair

Background

Tetralogy of Fallot (ToF) is the most common cyanotic congenital heart disease and the population of ToF repair survivors is growing rapidly. Adults with repaired ToF develop late complications. The aim of this study was to describe and analyze long-term follow-up of patients with repaired ToF.

Methods

This is a retrospective cohort study. Consecutive 83 patients with repaired ToF who did not undergo pulmonary valve replacement were included. Mean age of all patients was 30.5?±?10.7. There were 49 (59%) male. Patients were divided into two groups according to the time since the repair (<?25 years and?≥?25 years). The electrocardiographic (ECG), cardiopulmonary exercise testing (CPET), echocardiographic and cardiac magnetic resonance (CMR) data were reviewed retrospectively.

Results

In CPET values were not significantly different in the two groups. In CMR volumes of left and right ventricles were not significantly different in the two groups. There were no differences between the groups in ventricular ejection fraction, mass of ventricles, or pulmonary regurgitation fraction. Among all the patients, ejection fraction and left and right ventricle mass, indexed pulmonary regurgitation volume measured by CMR did not correlate with the time since repair. In ECG among all the patients, ejection fraction of the RV, measured in CMR, negatively correlated with QRS duration (r?=???0.43; p?<?0.001). There was a positive correlation between QRS duration and end diastolic volume of the RV (r?=?0.30; p?<?0.02), indexed end diastolic volume of the RV (r?=?0.29; p?=?0.04), RV mass (r?=?0.36; p?<?0.001) and left ventricle mass (r?=?0.26; p?=?0.04).

Conclusion

Long-term survival and clinical condition after surgical correction of ToF in infancy is generally good and the late functional status in ToF – operated patients could be excellent up to 25 years after the repair. QRS duration could be an utility and easy factor to assessment of right ventricular function.

Trial registration

The study protocol was approved by the local Ethics Committee. Each participant provided informed consent to participate in the study (license number 122.6120.88.2016 from 28.04.2016).

     

The impact of <Emphasis Type="Italic">MTHFR</Emphasis> 677C → T risk knowledge on changes in folate intake: findings from the Food4Me study

Background

It is hypothesised that individuals with knowledge of their genetic risk are more likely to make health-promoting dietary and lifestyle changes. The present study aims to test this hypothesis using data from the Food4Me study. This was a 6-month Internet-based randomised controlled trial conducted across seven centres in Europe where individuals received either general healthy eating advice or varying levels of personalised nutrition advice. Participants who received genotype-based personalised advice were informed whether they had the risk (CT/TT) (n?=?178) or non-risk (CC) (n?=?141) alleles of the methylenetetrahydrofolate reductase (MTHFR) gene in relation to cardiovascular health and the importance of a sufficient intake of folate. General linear model analysis was used to assess changes in folate intake between the MTHFR risk, MTHFR non-risk and control groups from baseline to month 6 of the intervention.

Results

There were no differences between the groups for age, gender or BMI. However, there was a significant difference in country distribution between the groups (p?=?0.010). Baseline folate intakes were 412?±?172, 391?±?190 and 410?±?186 μg per 10 MJ for the risk, non-risk and control groups, respectively. There were no significant differences between the three groups in terms of changes in folate intakes from baseline to month 6. Similarly, there were no changes in reported intake of food groups high in folate.

Conclusions

These results suggest that knowledge of MTHFR 677C?→?T genotype did not improve folate intake in participants with the risk variant compared with those with the non-risk variant.

Trial registration

ClinicalTrials.gov NCT01530139

     

Genetic risk factors for restenosis after percutaneous coronary intervention in Kazakh population

Background

After coronary stenting, the risk of developing restenosis is from 20 to 35 %. The aim of the present study is to investigate the association of genetic variation in candidate genes in patients diagnosed with restenosis in the Kazakh population.

Methods

Four hundred fifty-nine patients were recruited to the study; 91 patients were also diagnosed with diabetes and were excluded from the sampling. DNA was extracted with the salting-out method. The patients were genotyped for 53 single-nucleotide polymorphisms. Genotyping was performed on the QuantStudio 12K Flex (Life Technologies). Differences in distribution of BMI score among different genotype groups were compared by analysis of variance (ANOVA). Also, statistical analysis was performed using R and PLINK v.1.07. Haplotype frequencies and LD measures were estimated by using the software Haploview 4.2.

Results

A logistic regression analysis found a significant difference in restenosis rates for different genotypes. FGB (rs1800790) is significantly associated with restenosis after stenting (OR?=?2.924, P?=?2.3E?06, additive model) in the Kazakh population. CD14 (rs2569190) showed a significant association in the additive (OR?=?0.08033, P?=?2.11E?09) and dominant models (OR?=?0.05359, P?=?4.15E?11). NOS3 (rs1799983) was also highly associated with development of restenosis after stenting in additive (OR?=?20.05, P?=?2.74 E?12) and recessive models (OR?=?22.24, P?=?6.811E?10).

Conclusions

Our results indicate that FGB (rs1800790), CD14 (rs2569190), and NOS3 (rs1799983) SNPs could be genetic markers for development of restenosis in Kazakh population. Adjustment for potential confounder factor BMI gave almost the same results.