Risk stratification by systemic manifestations secondary to hemodynamic disorders of patients with severe tricuspid regurgitation.

BACKGROUND: Tricuspid regurgitation (TR) is a prevalent disease that triggers systemic pathological changes including cardiac, respiratory, hepatic and digestive, hematopoietic, renal and skin issues. The burden of extra-cardiac manifestations has not been well described in TR patients and the clinical impact is unknown. METHODS: Patients with severe or more-than-severe TR during hospitalization, who did not have any previous cardiac procedures, hemodynamically significant congenital heart disease or concomitant severe aortic or mitral valve disease, were retrospectively analyzed. Pre-specified criteria and diagnosis of baseline characteristics were used to evaluate the presence of extra-cardiac manifestations secondary to TR after excluding comorbidities that may also lead to corresponding abnormalities. Extra-cardiac involvements encompass respiratory, hepatic and, digestive, renal, hematopoietic and dermatic system. Staging criteria are defined as no extra-cardiac system involvement in Stage 1, one in Stage 2, at least two extra-cardiac involvements in Stage 3 and any end-stage organ failure in Stage 4. A telephone follow-up was conducted to record the composite endpoint namely all-cause death or cardiac rehospitalization after the index hospitalization. RESULTS: A total of 258 patients were identified with a median age of 73 (interquartile range [IQR]: 62-83) years and 52.3% were female. Severe TR and more-than-severe TR patients accounted for 92.6% and 7.4% of the cohort. There were 20.5%, 27.5%, 37.6% and 14.3% of patients from Stage 1 to 4 respectively. The follow-up time was at a median of 251 (IQR: 183-324) days. TR Patients in Stage 3&4 were at an increased risk with borderline statistical significance to experience the composite endpoint compared to patients in Stage 1&2 (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.0 to 3.7, P = 0.049). CONCLUSIONS: Approximately half of patients with at least severe TR presented with two or more extra-cardiac systemic manifestations, which may incur a 1.9-fold higher risk of all-cause death or cardiac rehospitalization than TR patients with one or less extra-cardiac involvement.

Comparison of patients with bicuspid and tricuspid aortic valve in transcatheter aortic valve implantation.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has emerged as a safe and effective alternative to surgery for aortic stenosis (AS). However, there are still differences in the procedural process and outcome of bicuspid aortic valve (BAV) treated with TAVI compared with tricuspid aortic valve. AREAS COVERED: This review paper aims to summarize the main characteristics and clinical evidence of TAVI in patients with bicuspid and tricuspid aortic valves and compare the outcomes of TAVI procedure. EXPERT OPINION: The use of TAVI in patients with BAV has shown similar clinical outcomes compared with tricuspid aortic valve. The efficacy of TAVI for challenging BAV anatomies remains a concern due to the lack of randomized trials. Detailed preprocedural planning is of great importance in low-surgical-risk BAV patients. A better understanding of which subtypes of BAV anatomy are at greater risk for adverse outcomes can potentially benefit the selection of TAVI or open-heart surgery in low surgical risk AS patients.

Reshaping bicuspid aortic valve stenosis with an hourglass-shaped balloon for transcatheter aortic valve replacement: A pilot study.

OBJECTIVES: We evaluated the safety and usefulness of preparatory anatomical reshaping with a geometric hourglass-shaped balloon to optimize transcatheter aortic valve replacement (TAVR) outcomes in bicuspid aortic valve (BAV) stenosis. BACKGROUND: TAVR has been increasingly performed for BAV stenosis; however, technical challenges remain. Procedural results are suboptimal given unfavorable valvular anatomies. METHODS: Eligible patients with BAV stenosis were enrolled to undergo aortic valve predilatation with the hourglass-shaped TAV8 balloon before TAVR using the self-expandable Venus A-Valve. Procedural details and outcomes were compared to a sequential group of patients with BAV who underwent TAVR with the same device following preparatory dilatation using a cylindrical balloon. RESULTS: A total of 22 patients were enrolled in the TAV8 group and 53 were included in the control group. Valve downsizing was less common in the TAV8 group (36.4 vs. 67.9%; p = .012). Stable valve release and optimal implant depth were consistently achieved in the TAV8 group with no requirement for a second valve (0 vs. 17.0%; p = .039) and with higher device success rates (100.0 vs 77.4%; p = .014). Residual aortic regurgitation graded as ≥mild was less common in the TAV8 group (13.6 vs 45.3%; p = .009). Mortality was similar (0 vs. 3.8%; p = 1); no major/disabling stroke or conversion to open-heart surgery was seen in either group within 30 days. CONCLUSIONS: Compared with standard cylindrical balloon valvuloplasty, preparatory reshaping with the hourglass-shaped balloon before self-expandable TAVR in BAV was associated with significantly better procedural results and may encourage more promising outcomes.

Classification and Prognosis Prediction from Histopathological Images of Hepatocellular Carcinoma by a Fully Automated Pipeline Based on Machine Learning.

OBJECTIVE: The aim of this study was to develop quantitative feature-based models from histopathological images to distinguish hepatocellular carcinoma (HCC) from adjacent normal tissue and predict the prognosis of HCC patients after surgical resection. METHODS: A fully automated pipeline was constructed using computational approaches to analyze the quantitative features of histopathological slides of HCC patients, in which the features were extracted from the hematoxylin and eosin (H&E)-stained whole-slide images of HCC patients from The Cancer Genome Atlas and tissue microarray images from West China Hospital. The extracted features were used to train the statistical models that classify tissue slides and predict patients' survival outcomes by machine-learning methods. RESULTS: A total of 1733 quantitative image features were extracted from each histopathological slide. The diagnostic classifier based on 31 features was able to successfully distinguish HCC from adjacent normal tissues in both the test [area under the receiver operating characteristic curve (AUC) 0.988] and external validation sets (AUC 0.886). The random-forest prognostic model using 46 features was able to significantly stratify patients in each set into longer- or shorter-term survival groups according to their assigned risk scores. Moreover, the prognostic model we constructed showed comparable predicting accuracy as TNM staging systems in predicting patients' survival at different time points after surgery. CONCLUSIONS: Our findings suggest that machine-learning models derived from image features can assist clinicians in HCC diagnosis and its prognosis prediction after hepatectomy.

Meta-Analysis of the Effectiveness and Safety of Transcatheter Aortic Valve Implantation Without Balloon Predilation.

Evidence regarding the safety and feasibility of transcatheter aortic valve implantation without balloon predilation (BP) is scarce. A literature search of PubMed, EMBASE, CENTRAL, and major conference proceedings was performed from January 2002 to July 2015. There were 18 studies incorporating 2,443 patients included in the present study. No differences were observed in the baseline characteristics between patients without BP (no-BP) and with BP. Compared with BP, no-BP had a shorter procedure time (no-BP vs BP, 124.2 vs 138.8 minutes, p = 0.008), used less-contrast medium (no-BP vs BP, 126.3 vs 156.3 ml, p = 0.0005) and had a higher success rate (odds ratio [OR] 2.24, 95% CI 1.40 to -3.58). In addition, no-BP was associated with lower incidences of permanent pacemaker implantation (OR 0.45, 95% CI 0.3 to 0.67), grade 2 or greater paravalvular leakage (OR 0.55, 95% CI 0.37 to 0.83), and stroke (OR 0.57, 95% CI 0.32 to 1.0). Furthermore, no-BP was associated with a 0.6-fold decreased risk for 30-day all-cause mortality (OR 0.60, 95% CI 0.39 to 0.92). However, the difference in the risk for permanent pacemaker implantation, grade 2, or higher aortic regurgitation, stroke was noted to be significant only in the subgroup of the CoreValve-dominating studies. In conclusion, no-BP before transcatheter aortic valve implantation was not only safe and feasible but was also associated with fewer complications and short-term mortality in selected patients especially using self-expandable valve.

The association between the Lys751Gln polymorphism in the XPD gene and the risk of bladder cancer.

The Lys751Gln polymorphism in the XPD gene have been suggested as a risk factor for bladder cancer, however the results were inconclusive. The aim of the current study is to assess the association by meta-analysis. A total of 15 case-control studies concerning the association between the XPD Lys751Gln polymorphism and bladder cancer risk were included in the meta-analysis. The results suggested that the Lys751Gln polymorphism was not associated with an increased risk of bladder cancer in the dominant model (OR = 1.03, 95 % CI 0.95-1.11, P = 0.53 for Lys/Gln+Gln/Gln vs. Lys/Lys) in overall analysis. In the subgroup analysis by ethnicity, no significant association was found in Caucasians or Asians. Other comparatives suggested a slight significant association between the polymorphism with the risk of bladder cancer in the recessive comparative (OR = 1.14, 95 % CI 1.02-1.29, P = 0.03). The current meta-analysis indicated that the Lys751Gln polymorphism in the XPD gene might be a risk factor for bladder cancer. In the future, more large-scale case-control studies are needed to validate our results.

Study on the association between the Arg194Trp polymorphism in the XRCC1 gene and the risk of hematological malignancies.

The association between the Arg194Trp polymorphism in the XRCC1 gene and the risk of hematological malignancies has been extensively investigated. However, the results were inconsistent. The objective of the current study is to investigate the association by meta-analysis. We searched the PubMed, Embase, CNKI, Wanfang, and Weipu databases, covering all studies until Aug. 7, 2013. Statistical analysis was performed by using the RevMan4.2 software and the Stata10.0 software. A total of 20 case-control studies concerning the Arg194Trp polymorphism were indentified from 19 articles. In total analysis, our results suggested that the Arg194Trp polymorphism was not associated with an increased/decreased risk of hematological malignancies (odds ratio (OR) = 1.01, 95 % confidence interval (CI) = 0.85-1.22, P = 0.87 for Arg/Trp+Trp/Trp vs. Arg/Arg). In the subgroup analysis by ethnicity, no significant association was found either among Asians (OR = 1.04, 95% CI = 0.84-1.29, P = 0.72) or among Europeans (OR = 1.04, 95% CI = 0.72-1.49, P = 0.83); in the subgroup analyses by cancer types, no significant association was found either among leukemia (OR = 1.10, 95% CI = 0.89-1.35, P = 0.39) or in lymphoma (OR = 0.83, 95% CI = 0.57-1.22, P = 0.35). The current meta-analysis indicated that the Arg194Trp polymorphism in the XRCC1 gene might be not a risk factor for hematological malignancies. In the future, more large-scale case-control studies are needed to validate these results.

The Arg188His polymorphism in the XRCC2 gene and the risk of cancer.

The Arg188His polymorphism in the XRCC2 gene has been suggested as a risk factor for cancer with inconclusive results. The aim of the current study is to investigate the association between the polymorphism with of cancer by meta-analysis. A total of 33 case-control studies from 27 publications were included for data analyses. The results suggested that the Arg188His polymorphism was not associated with increased/decreased risk of cancer in total analysis (Arg/His+His/His vs. Arg/Arg: OR = 0.98, 95% CI = 0.91-1.06). In the subgroup analysis by ethnicity, no statistical significant association was found in Europeans. In the subgroup analysis by cancer types, statistical significant association was found in ovarian cancer but not in other cancers. The current meta-analysis indicated that the Arg188His polymorphism in the XRCC2 gene might be a risk factor for ovarian cancer. In the future, more large-scale case-control studies are needed to validate our results.

The -786T > C polymorphism in the NOS3 gene is associated with increased cancer risk.

The -786T > C polymorphism in NOS3 gene may affect the DNA repair pathways and be associated with risk of cancer. However, the results of previous studies are inconsistent. The objective of this study is to investigate the association between the -786T > C polymorphism in NOS3 and risk of cancer by meta-analysis. We searched PubMed, Embase, CNKI, and Wanfang databases and the last search was updated on Sept. 20, 2013. Statistical analysis was performed using Revman4.2 and Stata10.0 software. A total of 9 case-control studies concerning 4,089 cases and 3,847 controls were included. The results suggested a significant association between the -786T > C polymorphism in NOS3 and cancer risk (CC vs. TT + CT; OR = 1.30, 95% CI = 1.07-1.57, P = 0.007) in total analysis. In the subgroup analysis by ethnicity and cancer types, significant associations were found in the breast cancer subgroup (OR 1.51, 95% CI 1.07-2.12; P = 0.02) and European subgroup (OR 1.26, 95% CI 1.01-1.58; P = 0.04). The current meta-analysis suggested that the -786T > C polymorphisms in NOS3 may be a risk factor for cancer. In the future, more case-control studies are needed to validate our results.

The Thr241Met polymorphism in the XRCC3 gene is associated with increased risk of cancer in Chinese mainland populations.

The Thr241Met polymorphism in XRCC3 gene may affect the DNA repair pathways and be associated with the risk of cancer. However, the results of previous studies are inconsistent in Chinese mainland populations. The objective of this study is to investigate the association between the Thr241Met polymorphism in XRCC3 gene and risk of cancer for the Chinese Mainland populations by meta-analysis. We searched PubMed database, Embase database, CNKI database, and Wanfang database, and the last search was updated on July 24, 2013. Statistical analysis was performed using RevMan4.2 and Stata10.0 software. Finally, a total of 23 case-control studies in 23 articles were included. The results suggested a significant association between the Thr241Met polymorphism in XRCC3 gene and cancer risk in Chinese mainland populations (Met/Met + Thr/Met vs. Thr/Thr: OR = 1.25, 95 % CI = 1.02-1.54, P = 0.04). In the subgroup analyses by cancer types, significant associations were found in cervical cancer and nasopharyngeal cancer. The current meta-analysis suggested that the Thr241Met polymorphism in the XRCC3 gene may be a risk factor for cancer in Chinese mainland populations. In the future, more case-control studies are needed to validate these results.

The association between the Arg280His polymorphism in the XRCC1 gene and the risk of hematological malignancies.

The associations between the Arg280His polymorphism in X-ray repair cross-complementing gene 1 (XRCC1 gene) and hematological malignancies have been extensively investigated. However, the results were inconsistent. The objective of the current study was to investigate the associations between the Arg280His polymorphism in XRCC1 gene and the risk of hematological malignancies by meta-analysis. We searched PubMed, Embase, CNKI, Wanfang, and Weipu databases, covering all studies until 07 Aug 2013. Statistical analysis was performed by using the Revman4.2 software and the Stata10.0 software. A total of 2,650 cases and 3,856 controls in 12 case-control studies concerning the Arg280His polymorphism were included. The results suggested that the Arg280His polymorphism might not be associated with risk of hematological malignancies (OR = 1.08, 95%CI = 0.86-1.35, P = 0.50). In the subgroup analyses by cancer types and ethnicity, no significant associations were found among different cancers or different ethnicities. The current meta-analysis indicated that the Arg280His polymorphism in the XRCC1 gene might not be a risk factor for hematological malignancies. In future, more large-scale case-control studies are needed to validate these results.

The polymorphisms in the MGMT gene and the risk of cancer: a meta-analysis.

Polymorphisms in the MGMT gene have been implicated in susceptibility to cancer, but the published studies have reported inconclusive results. The objective of the current study was to investigate the genetic risk of polymorphisms in the MGMT gene for cancer. A meta-analysis was carried out to analyze the association between polymorphisms in the MGMT gene and cancer risk. Five polymorphisms (Leu84Phe, Leu53Leu, Ile143Val, Lys178Arg, and -485C/A) with 98 case-control studies from 49 articles were analyzed. The results indicated that individuals who carried the Phe/Phe homozygote genotype of Leu84Phe had a 31 % increased risk of cancer compared with the Leu allele (Leu + Leu/Phe) carriers (odds ratio [OR] = 1.32, 95 % confidence interval [CI] = 1.15-1.52, P < 0.0001 for Phe/Phe vs. Phe/Leu + Leu/Leu). However, there was no significant association between the risk of cancer and the other four polymorphisms (Leu53Leu, Ile143Val, Lys178Arg, and -485C/A). In further stratified analyses for the Leu84Phe and Ile143Val polymorphisms, the increased risk of cancer remained in subgroups of Caucasians, patients with esophageal cancer for the Leu84Phe polymorphism, and patients with lung cancer for the Ile143Val polymorphism. Results from the current meta-analysis suggested that Leu84Phe and Ile143Val in the MGMT gene are risk factors for cancer. In the future, more studies should be performed to validate our results.

The Cdx-2 polymorphism in the VDR gene is associated with increased risk of cancer: a meta-analysis.

The Cdx-2 polymorphism in VDR gene has been extensively investigated for association with cancer risk, however, results of different studies have been inconsistent. The objective of this study is to assess the relationship of the Cdx-2 polymorphism in VDR and cancer risk by meta-analysis. All eligible case-control studies were searched in Pubmed, Embase, CNKI and Wanfang databases. Odds ratios (OR) with the 95 % confidence intervals (CI) were used to assess the association. A total of 12,906 cases and 13,700 controls in 18 case-control studies were included. The results indicated that the AA homozygote carriers had a 16 % increased risk of cancer, when compared with the homozygote GG and heterozygote AG (OR = 1.16, 95 % CI 1.05-1.29 for AA vs. GG+AG). In the subgroup analysis by ethnicity, significant elevated risks were associated with AA homozygote carriers in Caucasians (OR = 1.16, 95 % CI 1.01-1.33, and P = 0.04) and African Americans (OR = 1.31, 95 % CI 1.07-1.61, and P = 0.01). In the subgroup analysis by cancer types, the polymorphism was associated with increased risk of breast cancer (OR = 1.23, 95 % CI 1.04-1.46, and P = 0.02). This meta-analysis suggested that the Cdx-2 polymorphism of VDR gene would be a risk factor for cancer. To further evaluate gene-to-gene and gene-to-environmental interactions between polymorphisms of VDR gene and cancer risk, more studies with large groups of patients are required.

The association between the poly(A) polymorphism in the VDR gene and cancer risk: a meta-analysis.

The poly(A) polymorphism (L/S) in the VDR gene has been implicated in susceptibility of cancer, but a number of studies have reported inconclusive results. The aim of this study is to investigate the relationship between the poly(A) polymorphism in the VDR gene and cancer risk by meta-analysis. We searched PubMed database, EMBASE database, CNKI database, and Wanfang database, covering all studies until January 22, 2013. Statistical analysis was performed by using the software Revman4.2 and STATA 10.0. A total 8,186 cancer cases and 8,685 controls in 19 case-control studies from 15 studies were identified for data analysis. The results suggested that the S allele carriers (SS+SL) did not have an increased or decreased risk of cancer when compared with the homozygote LL carriers (odds ratio (OR) =0.96, 95 % CI=0.87-1.06, P=0.43 for SS+SL vs. LL). In addition, in the subgroup analysis by ethnicity and cancer type, no significant association was found among Caucasians, African-Americans, prostate cancer, or breast cancer. This current meta-analysis suggested that the poly(A) polymorphism in the VDR gene may not contribute to the risk of cancer. Future studies are needed to validate our findings.