Comparison of Acyclovir and Multistrain <Emphasis Type="Italic">Lactobacillus brevis</Emphasis> in Women with Recurrent Genital Herpes Infections: a Double-Blind,Randomized, Controlled Study

We performed a randomized double-blind controlled trial to compare the efficacy and safety of multistrain probiotic and acyclovir in women patients with recurrent genital herpes simplex virus type 2 (HSV-2) infections. Eighty-one patients enrolled in the study were being treated with multistrain Lactobacillus brevis one vaginal capsule every 12 h and oral acyclovir 400 mg twice daily for 6 months. Of 53 patients who completed both treatment courses, no important differences were identified between acyclovir and probiotic for the primary and secondary efficacy endpoint, resolution of episode (hazard ratio, 0.60; 95% CI, 0.3429 to 1.0663; P = 0.08), lesion healing time (hazard ratio, 0.57; 95% CI, 0.3034 to 1.0717, P = 0.08), viral shedding (hazard ratio, 0.54; 95% CI, 0.3027 to 0.9750, P = 0.04), and percentage of pain (hazard ratio, 0.48; 95% CI, 0.2708 to 0.8545, P = 0.01). The median time to first and second recurrence after treatment were 43 and 121 days in patients receiving acyclovir and 33 and 118 days in patients receiving probiotic (HR 2.61; 95% CI, 1.4427 to 4.7546, P = 0.001, and HR 0.62; 95% CI, 0.3500 to 1.1133, P = 0.1, respectively). No clinically important effects happened during the probiotic treatment but some of adverse events reported in patients taking acyclovir. Easy availability, low cost, and no side effect of L. brevis are valuable properties of probiotic therapy compared with acyclovir. Therefore, we concluded that multistrain L. brevis could play an important role in suppression of recurrent genital herpes simplex virus infection.     

Oxidative Stress-Related Genes in Type 2 Diabetes: Association Analysis and Their Clinical Impact

Worldwide prevalence of diabetes mellitus motivates a number of association studies to be conducted throughout the world. Eleven polymorphisms from nine candidate genes in oxidative stress pathway have been analyzed in eastern Indian type 2 diabetic patients (n = 145) and healthy controls (n = 100). Different biochemical parameters were also analyzed for their association with the disease. Significant associations were observed for rs2070424 A>G SOD1 (OR 3.91, 95% CI 2.265–8.142, P < 0.001), rs854573 A>G PON1 (OR 3.415, 95% CI 2.116–5.512, P < 0.001), rs6954345 G>C PON2 (OR 3.208, 95% CI 2.071–4.969, P < 0.001), RAGE rs1800624 ?374 T>A (OR 3.58, 95% CI 2.218–5.766, P < 0.001), and NOS3 ?786 T>C (OR 3.75, 95% CI 2.225–6.666, P < 0.001). Haplotype containing two risk alleles of PON1 and PON2 genes was significantly associated with disease (OR 8.34, 95% CI 1.554–44.804, P < 0.002). Our results suggest that carriers of major and efficient alleles of oxidative stress genes are more likely to survive the comorbid complications and single copy of risk allele is sufficient for developing the disease.     

Genetic variants in microRNA and microRNA biogenesis pathway genes and breast cancer risk among women of African ancestry

MicroRNAs (miRNA) regulate breast biology by binding to specific RNA sequences, leading to RNA degradation and inhibition of translation of their target genes. While germline genetic variations may disrupt some of these interactions between miRNAs and their targets, studies assessing the relationship between genetic variations in the miRNA network and breast cancer risk are still limited, particularly among women of African ancestry. We systematically put together a list of 822 and 10,468 genetic variants among primary miRNA sequences and 38 genes in the miRNA biogenesis pathway, respectively; and examined their association with breast cancer risk in the ROOT consortium which includes women of African ancestry. Findings were replicated in an independent consortium. Logistic regression was used to estimate the odds ratio (OR) and 95 % confidence intervals (CI). For overall breast cancer risk, three single-nucleotide polymorphisms (SNPs) in miRNA biogenesis genes DROSHA rs78393591 (OR = 0.69, 95 % CI: 0.55–0.88, P = 0.003), ESR1 rs523736 (OR = 0.88, 95 % CI: 0.82–0.95, P = 3.99 × 10^?4), and ZCCHC11 rs114101502 (OR = 1.33, 95 % CI: 1.11–1.59, P = 0.002), and one SNP in primary miRNA sequence (rs116159732 in miR-6826, OR = 0.74, 95 % CI: 0.63–0.89, P = 0.001) were found to have significant associations in both discovery and validation phases. In a subgroup analysis, two SNPs were associated with risk of estrogen receptor (ER)-negative breast cancer, and three SNPs were associated with risk of ER-positive breast cancer. Several variants in miRNA and miRNA biogenesis pathway genes were associated with breast cancer risk. Risk associations varied by ER status, suggesting potential new mechanisms in etiology.     

Association between <Emphasis Type="Italic">cagA</Emphasis>, <Emphasis Type="Italic">vacAi</Emphasis>, and <Emphasis Type="Italic">dupA</Emphasis> genes of <Emphasis Type="Italic">Helicobacter pylori</Emphasis> and gastroduodenal pathologies in Chilean patients

In addition to the already known cagA gene, novel genetic markers have been associated with Helicobacter pylori (H. pylori) virulence: the dupA and vacAi genes. These genes might play an important role as specific markers to determine the clinical outcome of the disease, especially the vacAi gene, which has been expected to be a good marker of severe pathologies like gastric adenocarcinoma. In the present study, the association of cagA, dupA, and vacAi genes with gastroduodenal pathologies in Chilean patients was studied. One hundred and thirty-two patients positive for H. pylori were divided into two groups—non-severe and severe gastric pathologies—and investigated for the presence of cagA, dupA, and vacAi H. pylori virulence genes by PCR. The cagA gene was detected in 20/132 patients (15.2%), the vacAi1 gene was detected in 54/132 patients (40.9%), the vacAi2 gene was detected in 26/132 patients (19.7%), and the dupA gene was detected in 50/132 (37.9%) patients. Logistic regression model analysis showed that the vacAi1 isoform gene in the infected strains and the severity of the diseases outcome were highly associated, causing severe gastric damage that may lead to gastric cancer (p < 0.0001; OR = 8.75; 95% CI 3.54–21.64). Conversely, cagA (p = 0.3507; OR = 1.62; 95% CI 0.59–4.45) and vacAi2 (p = 0.0114; OR = 3.09; 95% CI 1.26–7.60) genes were not associated with damage, while the dupA gene was associated significantly with non-severe clinical outcome (p = 0.0032; OR = 0.25; 95% CI 0.09–0.65). In addition, dupA gene exerts protection against severe gastric pathologies induced by vacAi1 by delaying the outcome of the disease by approximately 20 years.     

Mid-term and long-term safety and efficacy of bioresorbable vascular scaffolds versus metallic everolimus-eluting stents in coronary artery disease: A weighted meta-analysis of seven randomised controlled trials including 5577 patients

Aims

Mid- and long-term safety and efficacy of the Absorb bioresorbable vascular scaffold (BVS) have been studied in randomised trials; however, most were not individually powered for clinical endpoints. We performed a weighted meta-analysis comparing mid- and long-term outcomes in patients treated with the BVS compared with the Xience metallic stent.

Methods and results

Randomised trials comparing the BVS and Xience were identified by searching MEDLINE, EMBASE and conference abstracts. Seven trials were included (BVS n = 3258, Xience n = 2319) with follow-up between 1–3 years. The primary outcome of target lesion failure occurred more frequently in BVS compared with Xience [OR 1.34; 95% CI 1.11–1.62, p = 0.003]. Overall definite or probable device thrombosis occurred more frequently with the BVS [OR 2.86; 95% CI 1.88–4.36, p < 0.001] and this extended beyond 1 year of follow-up [OR 4.13; 95% CI 1.99–8.57, p < 0.001]. Clinically indicated or ischaemia driven target lesion revascularisation [OR 1.43; 95% CI 1.11–1.83, p = 0.005] and myocardial infarction (all MI) [OR 1.64; 95% CI 1.20–2.23, p = 0.002] were more frequently seen in the BVS compared with Xience. Rates of target vessel failure [OR 1.15; 95% CI 0.91–1.46, p = 0.25] and cardiac death [OR 0.91; 95% CI 0.57–1.46, p = 0.71] were not significantly different between BVS and Xience.

Conclusion

This meta-analysis shows a higher rate of target lesion failure and an almost threefold higher rate of device thrombosis in BVS compared with Xience, which extends beyond the first year. Device thrombosis did not lead to an overall increased (cardiac) mortality.

     

Association study of protamine 2 (<Emphasis Type="Italic">PRM2</Emphasis>) gene polymorphism with male infertility in Chinese Han population

Protamine 2 (PRM2), an essential nuclear protein expressed in sperm, is known to be involved in the spermatogenesis. Although PRM2 defects have been reported to be involved in male infertility, studies for the relationship between male infertility and PRM2 polymorphisms are inconclusive. With the purpose to determine the association of PRM2 variant with male infertility in Chinese Han population, one single nucleotide polymorphism locus G398C in PRM2 which might play a role in semen quality was selected and the variant frequency was analyzed in 144 idiopathic infertile men (case group) and 111 proven-fertile men (control group) in the study. Three genotypes were discovered in the studied population and statistical analysis showed that the frequencies of GG and GC genotypes of PRM2 G398C were significantly different between the fertile and infertile men (P < 0.05) and GC genotype was associated with increased risk of male infertility (OR = 1.795, 95 % CI 1.070–3.013, P = 0.026). Further, the C allele distribution was significantly elevated in infertile group (OR = 1.484, 95 % CI 1.001–2.200, P = 0.049). Moreover, we discovered that sperm motility, progressive motility, sperm DNA integrity as well as nuclear maturity rate of GG genotype presented the highest values and were dramatically different with that of CC genotype (P < 0.05). Our results gave the first evidence that PRM2 G398C polymorphism was associated with the pathogenesis of male infertility and its genetic variation was in relation to semen quality in Chinese Han population.     

Prognostic factors in infective endocarditis in general hospitals in the Netherlands

Introduction

Despite advances in treatment, infective endocarditis (IE) still ranks amongst the most lethal infectious diseases. We sought to determine prognostic factors in general hospitals in the Netherlands as research in this setting is scarce.

Results

Between 2004 and 2011, we identified 216 cases of IE, 30.1?% of which were prosthetic valve IE. This leads to an annual incidence of IE of 5.7 new cases per 100,000 persons per year. Women were less likely to undergo surgical intervention (OR = 1.96, 95?% CI 1.06–3.61, p = 0.031). Also, ageing was an independent prognostic factor for not receiving surgery in a multivariate analysis (annual OR = 1.04, 95?% CI 1.02–1.06, p < 0.001). Female sex was a prognostic factor for mortality (OR = 2.35, 95?% CI 1.29–4.28, p = 0.005). Age was also an independent prognostic factor for mortality (OR = 1.05, 95% CI 1.03–1.08, p < 0.001). Conservative treatment was a prognostic factor for mortality (OR = 3.39, 95?% CI 1.80–6.38, p < 0.001) whereas surgical intervention was an independent prognostic factor for adverse events (OR = 3.03, 95% CI 1.64–5.55, p < 0.001). Staphylococcus aureus was an independent prognostic factor for adverse events (OR = 2.05, 95?% CI 1.10–3.84, p = 0.024) but not for mortality.

Conclusion

This study shows that endocarditis in general hospitals has a high rate of morbidity and mortality. Even when treated, it ranks as one of the most lethal infectious diseases in the Netherlands, especially in women and the elderly.

     

Pastoralists’ Vulnerability to Trypanosomiasis in Maasai Steppe

Trypanosomiasis is a neglected tropical disease of both livestock and humans. Although pastoral communities of the Maasai Steppe have been able to adapt to trypanosomiasis in the past, their traditional strategies are now constrained by changes in climate and land regimes that affect their ability to move with their herds and continually shape the communities’ vulnerability to trypanosomiasis. Despite these constraints, information on communities’ vulnerability and adaptive capacity to trypanosomiasis is limited. A cross-sectional study was therefore conducted in Simanjiro and Monduli districts of the Maasai Steppe to establish pastoralists’ vulnerability to animal trypanosomiasis and factors that determined their adaptation strategies. A weighted overlay approach in ArcGIS 10.4 was used to analyze vulnerability levels while binomial and multinomial logistic regressions in R 3.3.2 were used to analyze the determinants of adaptation. Simanjiro district was the most vulnerable to trypanosomiasis. The majority (87.5%, n = 136) of the respondents were aware of trypanosomiasis in animals, but only 7.4% (n = 136) knew about the human form of the disease. Reported impacts of animal trypanosomiasis were low milk production (95.6%, n = 136), death of livestock (96.8%, n = 136) and emaciation of animals (99.9%, n = 136). Crop farming was the most frequently reported animal trypanosomiasis adaptation strategy (66%, n = 136). At a 95% confidence interval, accessibility to livestock extension services (β = 7.61, SE = 3.28, df = 135, P = 0.02), years of livestock keeping experience (β = 6.17, SE = 1.95, df = 135, P = 0.001), number of cattle owned (β = 5.85, SE = 2.70, df = 135, P = 0.03) and membership in associations (β = ? 4.11, SE = 1.79, df = 135, P = 0.02) had a significant impact on the probability of adapting to animal trypanosomiasis.     

Associations of MMP-2 −1306 C/T and MMP-9 −1562 C/T polymorphisms with breast cancer risk among different populations: a meta-analysis

The meta-analysis aims to investigate association between two matrix metalloproteinases (MMPs) polymorphisms (MMP-2 ?1306 C/T and MMP-9 ?1562 C/T) and breast cancer risk. Eligible studies were retrieved from relevant databases, based on predefined criteria. Quality assessment was evaluated by Newcastle–Ottawa Scale. Odds ratio (OR) with its 95% confidence interval (CI) was selected as the effect size for the meta-analysis. As a result, 13 studies were included. MMP-2 ?1306 C/T polymorphism was not significantly associated with breast cancer risk under all genetic models (P > 0.05). However, subgroup analysis stratified by ethnicity showed a significant association between MMP-2 ?1306 C/T polymorphism and reduced breast cancer risk in Asian populations under allelic model (OR 0.60, 95% CI 0.39–0.90, P = 0.02) and dominant model (OR 0.55, 95% CI 0.34–0.89, P = 0.02). MMP-9 ?1562 C/T polymorphism was significantly related to increased breast cancer risk under allelic model (OR 1.50, 95% CI 1.06–2.12, P = 0.02), additive model (OR 1.45, 95% CI 1.02–2.05, P = 0.04) and recessive model (OR 1.54, 95% CI 1.13–2.12, OR 0.007). A significant association between MMP-9 ?1562 C/T polymorphism and increased breast cancer risk in Caucasian was detected under most of the genetic models (P < 0.05). MMP-2 ?1306 C/T polymorphism might be significantly associated with reduced breast cancer risk in Asian, while MMP-9 ?1562 C/T might be closely related to increased breast cancer risk, especially in Caucasian.     

<Emphasis Type="Italic">A MCP</Emphasis>-<Emphasis Type="Italic">1</Emphasis> promoter polymorphism at G-2518A is associated with spontaneous preterm birth

Monocyte chemoattractant protein-1 (MCP-1) is an important chemokine involved in the pathogenesis of spontaneous preterm birth (SPTB). We examined whether the MCP-1 G-2518A polymorphism is associated with the risk of SPTB in a Chinese population. The MCP-1 G-2518A polymorphism was genotyped in 569 preterm singleton neonates and in 673 term neonates using polymerase chain reaction–restriction fragment length polymorphism analysis. The distribution of the MCP-1 G-2518A genotype and the allele frequencies between the SPTB patients and the controls were not significantly different in the overall sample. However, we found that the AA genotype was associated with significantly increased susceptibility to very SPTB (<32 weeks) [odds ratio (OR) 2.07; 95 % confidence interval (CI), 1.27–3.36; P = 0.005) and extremely SPTB (<28 weeks) (OR 2.74; 95 % CI, 1.10–6.72; P = 0.014) compared with ?2518G-positive genotypes (GG + GA genotypes). When extremely preterm neonates and very preterm neonates were combined, the AA genotype was also significantly associated with increased susceptibility to SPTB (OR 2.23; 95 % CI, 1.40–3.54; P < 0.001). The MCP-1 G-2518A polymorphism was not associated with increased susceptibility to SPTB in patients with premature rupture of the membranes (PROM) or in those without PROM. Our findings suggest that the MCP-1 G-2518A polymorphism may plays a role in mediating the susceptibility to SPTB in the Chinese population. Knowledge of genetic factors contributing to the pathogenesis of SPTB may have implications for screening and treatment of this disorder.     

Meta-analysis of ART outcomes in women with different preconception TSH levels

Background

To assess whether elevated thyroid-stimulating hormone (TSH) levels before conception can predict poor outcomes of assisted reproductive technology (ART).

Methods

Prior to July 2018, we searched the PubMed, EMBASE, COCHRANE, Google Scholar, and CNKI databases for studies. Retrospective or prospective reports that compared ART results in patients with subclinical hypothyroidism (SCH) with normal thyroid function were selected. Two reviewers separately reviewed each potential article for qualification, analyzed the quality of the studies according to the Newcastle-Ottawa scale, and extracted the data. The PRISMA guidelines were adopted.

Results

We selected a total of 18 publications that included 14,846 participants for this meta-analysis. When the TSH cut-off value for SCH was set at 2.5 mIU/L, no significant differences were observed in ART-related outcomes between SCH patients and normal women. The evaluated outcomes included the live birth rate (LBR) (OR: 0.93; 95% CI (0.77,1.12), P =?0.43), clinical pregnancy rate (CPR) (OR:1.02; 95% CI (0.90,1.17); P =?0.74), pregnancy rate (PR) (OR: 1.00; 95% CI (0.89,1.12); P =?0.99), and miscarriage rate (MR) (OR:1.24; 95% CI (0.85, 1.80); P =?0.26). Furthermore, when a higher TSH level was used as the cut-off value to diagnose SCH (i.e., 3.5–5 mIU/L), a significant difference was found in the MR (OR: 1.91; 95% CI (1.09, 3.35); P =?0.02) between the two groups of ART-treated women. However, when a broader cut-off value was used to define SCH, no significant differences were observed in the LBR (OR: 0.72; 95% CI (0.47,1.11); P =?0.14), CPR (OR: 0.82; 95% CI (0.66,1.00); P =?0.052), or PR (OR: 1.07; 95% CI (0.72,1.60); P =?0.74) between the two groups of ART-treated women.

Conclusion

No difference was observed in ART outcomes when a TSH cut-off value of 2.5 mIU/L was used. However, when a broader TSH cut-off value was used, preconception SCH resulted in a higher miscarriage rate than in normal women.

     

The efficacy and feasibility of total reconstruction versus nontotal reconstruction of the pelvic floor on short-term and long-term urinary continence rates after radical prostatectomy: a meta-analysis

Background

Recently, total pelvic floor reconstruction (TR) has been the treatment of choice for improving urinary incontinence (UI) after radical prostatectomy (RP). However, the superiority of TR with respect to urinary continence recovery following RP remains controversial. This study identified the effect of TR versus nonTR of the pelvic floor on short-term and long-term continence rates after RP.

Methods

A literature search was performed in November 2017 using the PubMed, Embase, and Web of Science databases. Only comparative research or clinical studies reporting urinary continence outcomes was included in the meta-analysis, and the quality of evidence was evaluated using the 2011 Level of Evidence for therapy research.

Results

We analyzed ten studies reporting urinary continence rates after RP at one or more postoperative time points (1, 2, 4, 12, 24, and 52 weeks). TR was associated with significantly better urinary continence outcomes at 1 week (OR 2.76, 95% CI 1.58–4.84, P?<?0.001), 2 weeks (OR 2.57, 95% CI 1.74–3.80, P?<?0.001), 4 weeks (OR 2.61, 95% CI 1.56–4.38, P?<?0.001), 12 weeks (OR 4.33, 95% CI 2.01–9.33, P?<?0.001), 24 weeks (OR 3.83, 95% CI 1.54–9.55, P?=?0.004), 52 weeks (OR 4.10, 95% CI 1.80–9.38, P?<?0.001) after RP. There was no difference in the rate of complications between the two arms (OR 0.54, 95% CI 0.19–1.54, P?=?0.25).

Conclusions

Compared with nonTR, TR is significantly and positively associated with a return to continence but not with complication rate in men following RP, suggesting that TR may be useful for decreasing the urinary incontinence rate after surgery.

     

A novel haplotype within C-reactive protein gene influences CRP levels and coronary heart disease risk in Northwest Indians

According to several epidemiological and clinical studies, the concentration of C-reactive protein (CRP) in blood is associated with the risk of coronary heart disease (CHD). However, these studies are limited in high incidence and prevalence area of North-West India. The present case control study investigated the contribution of three relevant CRP single nucleotide polymorphisms: ?717A>G located in the promoter region (rs2794521), +1059G>C on exon2 (rs1800947) and +1444C>T in the 3′ UTR (rs1130864) in 180 angiographically verified CHD cases and 175 control subjects. Minor allele frequencies (G, C and T) of rs2794521, rs1800947 and rs1130864 are observed to be 21.1, 11.7, 29.4 and 11.4, 10.0, 19.7 % in CHD cases and controls respectively. AA genotype of ?717A>G and TT genotype of +1444C>T were significantly associated (P = 0.02 & 0.03 respectively) with the risk of CHD whereas, +1059G and +1444T were found to be strongly related (P = 0.023 & P = 0.008 respectively) with multivariable adjusted CRP levels. AGT Haplotype was significantly associated with the adjusted CRP levels (P < 0.05). Disease association analysis revealed that haplotype AGT influences CHD risk (OR 2.4, 95 % CI 1.23–4.84, P = 0.006) which exacerbates after correcting the confounding effects of risk variables (OR 2.5, 95 % CI 1.27–4.99, P = 0.004). With the global index of Akaike information criterion, it has been observed that the carrying each single unit of this susceptibility haplotype increases CHD risk by a value of 2.41 ± 0.439 (β ± SE) in the recessive mode.     

A prospective study of dietary and supplemental zinc intake and risk of type 2 diabetes depending on genetic variation in <Emphasis Type="Italic">SLC30A8</Emphasis>

Background

The solute carrier family 30 member 8 gene (SLC30A8) encodes a zinc transporter in the pancreatic beta cells and the major C-allele of a missense variant (rs13266634; C/T; R325W) in SLC30A8 is associated with an increased risk of type 2 diabetes (T2D). We hypothesized that the association between zinc intake and T2D may be modified by the SLC30A8 genotype.

Results

We carried out a prospective study among subjects with no history cardio-metabolic diseases in the Malmö Diet and Cancer Study cohort (N = 26,132, 38% men; 86% with genotype data). Zinc intake was assessed using a diet questionnaire and food record. During a median follow-up of 19 years, 3676 T2D cases occurred. A BMI-stratified Cox proportional hazards regression model with attained age as the time scale was used to model the association between total and dietary zinc intake, zinc supplement use, zinc to iron ratio, and risk of T2D adjusting for putative confounding factors.The median total zinc intake was 11.4 mg/day, and the median dietary zinc intake was 10.7 mg/day. Zinc supplement users (17%) had a median total zinc intake of 22.4 mg/day. Dietary zinc intake was associated with increased risk of T2D (P _trend < 0.0001). In contrast, we observed a lower risk of T2D among zinc supplement users (HR = 0.79, 95% CI 0.70–0.89). The SLC30A8 CC genotype was associated with a higher risk of T2D (HR = 1.16, 95% CI 1.07–1.24), and the effect was stronger among subjects with higher BMI (P _interaction = 0.007). We observed no significant modification of the zinc-T2D associations by SLC30A8 genotype. However, a three-way interaction between SLC30A8 genotype, BMI, and zinc to iron ratio was observed (P _interaction = 0.007). A high zinc to iron ratio conferred a protective associated effect on T2D risk among obese subjects, and the effect was significantly more pronounced among T-allele carriers.

Conclusions

Zinc supplementation and a high zinc to iron intake ratio may lower the risk of T2D, but these associations could be modified by obesity and the SLC30A8 genotype. The findings implicate that when considering zinc supplementation for T2D prevention, both obesity status and SLC30A8 genotype may need to be accounted for.

     

Impact of neutrophil-to-lymphocyte ratio on periprocedural myocardial infarction in patients undergoing non-urgent percutaneous coronary revascularisation

Background

Pro-thrombotic conditions importantly influence myocardial perfusion and procedural results after percutaneous coronary intervention (PCI). The neutrophil-to-lymphocyte ratio (NLR) has emerged as a predictor of cardiovascular events and of long-term prognosis, especially in ST-elevation myocardial infarction patients undergoing primary PCI. The aim of our study was to evaluate the role of NLR on periprocedural myocardial infarction (MI) in patients undergoing non-urgent PCI.

Methods

In a consecutive cohort of 1542 patients undergoing PCI, myonecrosis biomarkers were determined at 6, 12, 24 and 48 hours post-procedure. Patients were divided into quintiles according to NLR values. Periprocedural myonecrosis was defined as a troponin I increase of 3 times the upper limit of normal or as 50?% of an elevated baseline value, whereas periprocedural MI was defined as a CK-MB increase of 3 times the upper limit of normal or 50?% of baseline.

Results

Higher NLR was related to age, established risk factors and cardiovascular history. NLR was associated with severe coronary artery disease (p = 0.009), tighter stenosis (p < 0.001), coronary calcifications (p = 0.005), intracoronary thrombus or thrombectomy use (p < 0.001), TIMI flow pre- and post-PCI (p < 0.001), and inversely to restenosis (p = 0.04) and use of a drug-eluting stent (p = 0.001). NLR did not influence the occurrence of myonecrosis (p = 0.75; adjusted OR (95?% CI) = 0.99 (0.63–1.54), p = 0.96), but was associated with a higher occurrence of periprocedural MI, even after correction for baseline differences (p = 0.03; adjusted OR (95?% CI) = 1.33 (1.02–2.3), p = 0.02), with NLR ≥ 3 best predicting the risk of periprocedural MI at the receiver operating characteristic curve analysis.

Conclusion

In patients undergoing non-urgent PCI, a higher NLR increases the risk of periprocedural MI, especially for values ≥ 3.

     

Effects of Common Polymorphisms in the MTHFR and <Emphasis Type="Italic">ACE</Emphasis> Genes on Diabetic Peripheral Neuropathy Progression: a Meta-Analysis

Diabetic peripheral neuropathy (DPN) is a microvascular complication of diabetes mellitus. The aim of this meta-analysis was to evaluate the effects of methylenetetrahydrofolate reductase (MTHFR) 677 C>T and ACE I/D polymorphisms in the development of DPN. We systematically reviewed published studies on MTHFR 677 C>T and ACE I/D polymorphisms and DPN found in various types of electronic databases. Strengthening the Reporting of Observational studies in Epidemiology (STROBE) quality score systems were used to determine the quality of the articles selected for inclusion. Odds ratios (ORs) and its corresponding 95 % confidence interval (95 % CI) were calculated. We used STATA statistical software (version 12.0, Stata Corporation, College Station, TX, USA) to deal with statistical data. Our results indicated an association of ACE D>I mutation (OR?=?1.43, 95 % CI 1.12–1.83, P?=?0.004) and MTHFR 677 C>T mutation (OR?=?1.43, 95 % CI 1.08–1.90, P?=?0.014) with DPN under the allele model, and similar results were also found under the dominant model (all P?<?0.05). Subgroup analysis by country indicated that the MTHFR 677 C>T polymorphism may be the main risk factor for DPN in Turkey under four genetic models. ACE D>I mutation was correlated with DPN in Japanese and Pakistani populations in the majority of groups. The relationships of MTHFR 677 C>T and ACE I/D polymorphisms with DPN patients presented in this meta-analyses support the view that the MTHFR and ACE genes might play an important role in the development of DPN.     

The Impact of MMP-2 and Its Specific Inhibitor TIMP-2 Expression on the WHO Grade and Prognosis of Gliomas in Chinese Population: a Meta-Analysis

So far, the prognostic value of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of matrix metalloproteinase 2 (TIMP-2) expressions in patients with gliomas has been widely reported, especially in China. But, the results were inconsistent. Thus, we conducted a meta-analysis to determine the correlation of MMP-2 and TIMP-2 expressions with the prognosis of patients with gliomas. Identical search strategies were used to search relevant literature in electronic databases updated to May 1, 2015, and odds ratios (ORs) with 95 % confidence intervals (95 % CIs) were estimated. Funnel plots and Egger’s tests were conducted for the evaluation of publication bias, and heterogeneity and sensitivity were also analyzed. Finally, a total of 25 studies involving 1572 patients were included in the meta-analysis. Coincidentally, all these studies were conducted in Chinese population. It was found that MMP-2 expression was significantly associated with high-WHO grade gliomas (n?=?24, OR?=?6.54, CI?=?4.98–8.60; I ²?=?0 %, P?=?0.911) and poor overall survival (OS), while it did not correlate to age (n?=?2, OR?=?0.78, CI?=?0.35–1.74; I ²?=?0 %, P?=?0.621) and gender (n?=?2, OR?=?1.15, CI?=?0.51–2.62; I ²?=?0 %, P?=?0.995). Moreover, the results of the pooled analysis indicated that there was no association between TIMP-2 expression and the WHO grade of gliomas (n?=?7, OR?=?1.02, 95 % CI?=?0.68–1.54; I ²?=?71.4 %, P?=?0.002), but the ratio of MMP-2 and TIMP-2 (MMP-2/TIMP-2) rose with the increase of the WHO grade of gliomas. In conclusion, there was no correlation between TIMP-2 expression and the WHO grade of gliomas, while MMP-2 expression was potently associated with high-WHO grade of gliomas.     

Clinical and economic impact of the introduction of a nucleic acid amplification assay for <Emphasis Type="Italic">Clostridium difficile</Emphasis>

Background

The clinical outcomes and cost implications of a diagnostic shift from an EIA- to PCR-based assay for Clostridium difficile infection (CDI) have not been completely described in the literature.

Methods

The impact of the PCR-based assay on the incidence and duration of CDI therapy was compared to the EIA assay for patients with a negative CDI diagnostic result. Secondary clinical and economic outcomes were also evaluated. Independent predictors of receipt of antibiotic therapy were assessed via logistic regression.

Results

141 EIA and 140 PCR patients were included. Significantly more patients were started or continued on anti-CDI antibiotic therapy after a known negative assay result in the EIA group (26 patients vs. 8 patients, P = 0.002). Duration of antibiotic therapy after a known negative result was significantly shorter in the PCR group (1 vs. 4 days, P = 0.029) and a 23% reduction in the number of tests obtained per patient was observed (1.41 ± 0.86 vs. 1.82 ± 1.35, P = 0.007). The over fourfold difference in per-test cost of the EIA assay ($8.33 vs. $42.86, P < 0.0001) was offset by the overall medication costs required for the increased treatment in the EIA group ($546.60 vs. $188.96, P = 0.191). Utilization of the EIA-based CDI assay was associated with increased odds of CDI treatment after a negative test (aOR 4.71, 95% CI 1.93–11.46, P = 0.001).

Conclusion

The transition from an EIA to PCR-based assay for diagnosing CDI resulted in a significant decrease in the number of patients treated and the duration of treatment in response to a negative test result. This significant decrease in treatment resulted in decreased costs offsetting the utilization of a more expensive molecular test for patients with a negative CDI diagnostic result.

     

Association between glutathione S-transferases M1, T1 and P1 gene polymorphisms and prostate cancer in Koreans

Prostate cancer (PCa) is the most commonly diagnosed cancer in the developed world, and the incidence of this cancer is rising rapidly in many countries. Several polymorphic genes encoding enzymes involved carcinogenesis have been studied as potential risk factor of prostate cancer. Genetic polymorphisms in glutathione S-transferases M1 (GSTM1), T1 (GSTT1) and P1 (GSTP1) genes have been constantly reported to have a meaningful effect on prostate cancer risk. But other surveys of this relationship have yielded inconsistent results. To assess the possible contribution of the GSTM1, GSTT1, and GSTP1 gene polymorphisms in prostate cancer, we performed a population-based study of 139 prostate cancer patients and 115 healthy controls based on their genotype distributions of the genes. There were no differences in distributions of genotype frequencies of GSTM1 and GSTP1 polymorphisms between prostate cancer patients and controls (OR 1.60, 95 % CI 0.886–2.860 for GSTM1 and OR 1.38, 95 % CI 0.739–2.577 for GSTP1). In contrast, the distribution of GSTT1-null genotype is significantly different between the prostate cancer case and controls (OR 0.26, 95 % CI 0.128–0.518, p < 0.001). Meanwhile, GSTP1 I/V and V/V genotypes were significantly associated with prostate cancer where the PSA level was more than 10.0 (OR 2.73, 95 % CI 1.319–5.639, p = 0.006). Thus, our data imply that the GSTT1-null genotype may not be a risk factor but a protective factor of prostate cancer and GSTP1 Val allele is a risk factor for the prostate cancer where the PSA level was high, although functional studies with larger sample size are necessary to elucidate these findings.     

Genetic polymorphisms of patients on stable warfarin maintenance therapy in a Ghanaian population

Background

Warfarin is a widely prescribed anticoagulant with narrow therapeutic window for thromboembolic events. Warfarin displays large individual variability in dose requirements. The purpose of this study is to assess the contribution of patient-specific and genetic risk factors to dose requirements of patients on either high or low warfarin maintenance dose in Ghana. Blood samples were collected from 141 (62 males, 79 females) Ghanaian patients on stable warfarin dose to determine their INR. Influence of patient specific factors and gene variations within VKORC1, CYP2C9 and CYP4F2 were determined in patients on either high or low warfarin maintenance dose.

Results

One hundred and forty-one patients took part in the study with 79 (56%) participants being Female. The median age of the study participants was 48 years [IQR: 34–58]. The median duration for patients to be on warfarin therapy was 24 months [IQR: 10–72]. Majority of the study participants (80.9%, n = 114) did not have any side effects to warfarin. CYP2C9*2 and CYP2C9*3 variant alleles were not detected. VKORC1 variant allele was observed at 6% and CYP4F2 variant allele was observed at 41%. Duration of patients on warfarin therapy was marginally associated with high warfarin dose (adjusted OR = 1.01 [95% CI 1.00–1.02], p = 0.033) while the odds of heterozygous individuals (G/A) for VKORC1 gene to have high warfarin dose compared to persons with homozygous (G/G) (adjusted OR = 0.06 [95% CI 0.01–0.63], p = 0.019). Age, gender, diagnosis, presence of side effects and other medications were not associated with warfarin dose (p = 0.05).

Conclusion

This study provides data on VKORC1 and CYP4F2 variants among an indigenous African population. Duration of patients on warfarin therapy was marginally associated with high warfarin dose. CYP2C9*2 and *3 variants were not detected and may not be the most important genetic factor for warfarin maintenance dose among Ghanaians.