Genetic polymorphisms in oxidative stress‐related genes are associated with outcomes following treatment for aggressive B‐cell non‐Hodgkin lymphoma

Variable survival outcomes are seen following treatment for aggressive non‐Hodgkin lymphoma (NHL). This study examined whether outcomes for aggressive B‐cell NHL are associated with single nucleotide polymorphisms (SNPs) in oxidative stress‐related genes, which can alter drug metabolism and immune responses. Genotypes for 53 SNPs in 29 genes were determined for 337 patients given anthracycline‐based therapies. Their associations with progression‐free survival (PFS) and overall survival (OS) were estimated by Cox proportional hazard regression; associations with hematologic toxicity were estimated by logistic regression. To validate the findings, the top three SNPs were tested in an independent cohort of 572 DLBCL patients. The top SNPs associated with PFS in the discovery cohort were the rare homozygotes for MPO rs2243828 (hazard ratio [HR] = 1.87, 95% confidence interval [CI] = 1.14–3.06, P = 0.013), AKR1C3 rs10508293 (HR = 2.09, 95% CI = 1.28–3.41, P = 0.0032) and NCF4 rs1883112 (HR = 0.66, 95% CI = 0.43–1.02, P = 0.06). The association of the NCF4 SNP with PFS was replicated in the validation dataset (HR = 0.66, 95% CI = 0.44–1.01, P = 0.05) and the meta‐analysis was significant (HR = 0.66, 95% CI = 0.49–0.89, P < 0.01). The association of the MPO SNP was attenuated in the validation dataset, while the meta‐analysis remained significant (HR = 1.64, 95% CI = 1.12–2.41). These two SNPs showed similar trends with OS in the meta‐analysis (for NCF4, HR = 0.72, 95% CI = 0.51–1.02, P = 0.07 and for MPO, HR = 2.06, 95% CI = 1.36–3.12, P < 0.01). In addition, patients with the rare homozygote of the NCF4 SNP had an increased risk of hematologic toxicity. We concluded that genetic variations in NCF4 may contribute to treatment outcomes for patients with aggressive NHL. Am. J. Hematol. 89:639–645, 2014. © 2014 Wiley Periodicals, Inc.     

Predictors of moderate‐to‐severe paravalvular aortic regurgitation immediately after corevalve implantation and the impact of postdilatation

Objective : To investigate the predictors of moderate‐to‐severe aortic regurgitation (AR≥2+) after CoreValve implantation and evaluate the feasibility and safety of postdilatation in reducing the degree of AR. Background : Although transcatheter aortic valve implantation is an alternative treatment for high surgical risk patients with severe aortic stenosis, post‐implantation paravalvular AR remains a complication. Methods : From July 2008 to July 2010, we enrolled 79 consecutive patients with severe aortic stenosis who underwent CoreValve implantation. Results : On univariable analysis, the predictors of AR≥2+ immediately after CoreValve implantation were: larger annulus size, low implantation, prosthesis mismatch, chronic renal insufficiency, a history of heart failure, and peripheral vascular disease. On multivariable analysis, the independent predictors of AR≥2+ were: larger annulus diameter (OR 1.78, 95%CI 1.25–2.55; P = 0.002), low implantation (OR 3.67, 95%CI 1.01–13.35, P = 0.05), and peripheral vascular disease (OR 3.54, 95%CI 1.19–10.56, P = 0.02). Post‐CoreValve implantation, AR ≥ 2 was seen in 40.5% (32/79). Twenty‐one patients underwent postdilatation with improvement in AR grade in the majority (17/21). Of the four patients who did not respond to postdilatation, two underwent valve‐in‐valve implantation. In one patient, the valve was pulled more proximally by the snare technique. The remaining 10 patients were treated conservatively. Conclusion : The appropriate strategy for treating patients with AR≥2+ depends on the causes and severity of AR post‐TAVI. This study suggests that we should carefully select the size of CoreValve prosthesis to prevent prosthesis mismatch, especially when implanted in larger annulus sizes. For valves implanted in the appropriate position, postdilatation appears effective in reducing the degree of AR. © 2011 Wiley‐Liss, Inc.     

Hemophagocytosis and relapsed peripheral T‐cell lymphoma

Although the survival of patients with hairy cell leukemia (HCL) has been improved by the therapeutic introduction of interferon α and purine analogs, it is still worsened by complications such as severe infections. In this long‐term study, we identified factors influencing patient outcomes in 73 patients with HCL. Median age at diagnosis was 53 yr and the gender ratio (M/F) was 2.3. At the time of HCL diagnosis, 60 patients (82%) were symptomatic and 22 of these had an infection. After a median follow‐up of 13 yr, eight patients had died of secondary cancer (n = 2), HCL progression (n = 1) and age‐related complications (n = 5). The 10‐yr overall survival (OS), progression‐free survival and relapse rates were 91 ± 3%, 14 ± 5% and 87 ± 5%, respectively. In multivariate analyses, age >53 yr was the only factor adversely influencing OS and secondary cancer incidence, with adjusted hazard ratio (HR) of 9.30 (95%CI, 1.15–76.6; P = 0.037) and 2.80 (95%CI, 1.05–7.71; P = 0.04), respectively. Eleven patients developed severe infections. Absolute lymphocyte count (<1 × 10⁹/L) at diagnosis was the only factor influencing the occurrence of severe infections, with an adjusted HR of 4.01 (P = 0.007). Strikingly, we did not observe any significant correlation between neutrophil or monocyte counts and the incidence of infection. We confirmed long‐term survival in HCL but found a high incidence of infection – even late in the course of the disease. The absolute lymphocyte count at diagnosis is a risk factor for the occurrence of severe infections. In addition to careful monitoring of infections, prompt initiation of anti‐HCL treatment should be considered in patients with low lymphocyte counts.     

Plasma D‐Dimer Level and the Failure of Forearm Autologous Arteriovenous Fistula in Patients With End‐Stage Renal Disease

Failed autologous arteriovenous fistula (AVF) is a major issue in the creation of functional hemodialysis vascular access. To date, the relationship between D‐dimer and AVF failure is still uncertain. Hence, we conducted a retrospective cohort study to explore the patency rate of forearm AVFs and to clarify whether plasma D‐dimer level can predict the failure of AVFs. In this study, 290 ESRD patients (the mean age 54.1 ± 14.6 years, 63.8% of them were males) receiving forearm AVFs surgery were consecutively enrolled with a median follow‐up time of 34 months. Primary patency rates and risk factors associated with AVFs failure were explored by the Kaplan–Meier method or Cox proportional hazards model. Patients were divided into two groups based on the median level of D‐dimer (group 1 <1.1 mg/L and group 2 ≥1.1 mg/L). The Kaplan–Meier survival analysis demonstrated that the patency of AVF in group 1 was similar in group 2, which were 92.4% versus 88.9%, 84.8% versus 84.0%, 80.0% versus 79.2%, 76.7% versus 78.5%, and 76.7% versus 78.5% at 12, 24, 36, 48, and 60 months (Log‐rank test, P = 0.8), respectively. In the crude analysis, D‐dimer (per 1 mg/L increase) was independently associated with AVFs failure, with OR of 1.08 (95% CI, 1.02–1.15). However, after adjusting for potential confounders, the D‐dimer (per 1 mg/L increase) was not associated with the AVFs failure (OR = 1.06, 95% CI = 0.99–1.13). This study did not find that the plasma D‐dimer level can predict the failure of forearm AVFs.     

Effect of sex difference in clinical presentation (stable coronary artery disease vs unstable angina pectoris or non‐ST‐elevation myocardial infarction vs ST‐elevation myocardial infarction) on 2‐year outcomes in patients undergoing percutaneous coronary intervention

Objective

To determine whether there is a difference in 2‐year prognosis among patients across the spectrum of coronary artery disease undergoing percutaneous coronary intervention (PCI).

Methods

We analyzed all consecutive patients undergoing PCI at a single center from 1/1‐12/31/2013. Clinical presentations were compared between sexes according to baseline clinical, angiographic, and procedural characteristics and 2‐year (mean 730 ± 30‐day) outcomes.

Results

We grouped 10 724 consecutive patients based on sex and clinical presentation. Among patients with ST‐elevation myocardial infarction (STEMI), rates of all‐cause death (6.7% vs 1.4%) and cardiac death (3.8% vs 1.1%) were significantly higher in women than in men (P < 0.05), but these rates did not differ between men and women with stable coronary artery disease (SCAD) and non‐ST‐elevation acute coronary syndrome ((NSTE‐ACS). Incidence of major bleeding was greater than in men only in those women presenting with ACS. After multivariable adjustment, female sex was not an independent predictor of outcomes in STEMI (hazard ratio [HR] for all‐cause death: 1.33, 95% confidence interval [CI]:0.52‐3.38; P = 0.55; HR for cardiac death: 0.69, 95%CI: 0.23‐2.09, P = 0.51], but was still an independent predictor of bleeding in STEMI (HR: 3.53, 95%CI: 1.26‐9.91, P = 0.017).

Conclusion

Among STEMI patients, women had worse 2‐year mortality after PCI therapy, but female sex was not an independent predictor of mortality after adjustment for baseline characteristics. In STEMI patients, women were at higher bleeding risk than men after PCI, even after multivariable adjustment.     

Efficacy of Long‐Term Treatment With Tolvaptan to Prolong the Time Until Dialysis Initiation in Patients With Chronic Kidney Disease and Heart Failure

The short‐term effectiveness of tolvaptan (TLV) against heart failure has been established. TLV is known to decrease the worsening of renal function more than loop diuretics. Long‐term TLV administration decreases the rate of re‐hospitalization in heart failure and prevents deterioration of kidney function. If repeated hospitalization for heart failure can be prevented in patients having concurrent chronic kidney disease (CKD), the period until dialysis initiation may be prolonged. We investigated whether long‐term TLV management can extend the period until dialysis initiation in patients with CKD and heart failure. A retrospective, observational study was conducted among patients with CKD stage G4 and G5 admitted because of heart failure between April 2013 and July 2018. They were divided into those with TLV and those without TLV. They were followed up until August 2018 and relevant data was collected. Data from 115 patients (68 men and 47 women), with a mean age of 73.4 ± 11.9 (median 76.0 and IQR 66.5–82.0) years and a mean eGFR of 11.8 ± 5.7 (median 9.9 and IQR 7.5–14.8) mL/min/1.73m² were included in the analysis. Twenty‐five patients had received long‐term TLV treatment, and 90 had not. Multivariate analysis after adjustment showed that long‐term use of TLV significantly lowered the hazard ratio (HR) for time taken to reach dialysis initiation (HR: 0.3286, 95%CI: 0.1282–0.8423, P = 0.0205). Propensity score‐matched analysis showed similar results (HR: 0.3220, 95%CI: 0.1107–0.9369, P = 0.0376). In patients with CKD G4 and G5 and heart failure, long‐term treatment with TLV can prolong the time until dialysis initiation.     

Survival analysis of platinum‐refractory patients with advanced esophageal cancer treated with docetaxel or best supportive care alone: a retrospective study

The survival benefit of second‐line chemotherapy with docetaxel in platinum‐refractory patients with advanced esophageal cancer (AEC) remains unclear. A retrospective analysis of AEC patients with Eastern Cooperative Oncology Group performance status (PS) ≤ 2 was performed, and major organ functions were preserved, who determined to receive docetaxel or best supportive care (BSC) alone after failure of platinum‐based chemotherapy. The post‐progression survival (PPS), defined as survival time after disease progression following platinum‐based chemotherapy, was analyzed by multivariate Cox regression analysis using factors identified as significant in univariate analysis of various 20 characteristics (age, sex, PS, primary tumor location, etc) including Glasgow prognostic score (GPS), which is a well‐known prognostic factor in many malignant tumors. Sixty‐six and 45 patients were determined to receive docetaxel and BSC between January 2007 and December 2011, respectively. The median PPS was 5.4 months (95% confidence interval [CI] 4.8–6.0) in the docetaxel group and 3.3 months (95% CI 2.5–4.0) in the BSC group (hazard ratio [HR] 0.56, 95% CI 0.38–0.84, P = 0.005). Univariate analysis revealed six significant factors: treatment, PS, GPS, number of metastatic organs, liver metastasis, and bone metastasis. Multivariate analysis including these significant factors revealed three independent prognostic factors: docetaxel treatment (HR 0.62, 95% CI 0.39–0.99, P = 0.043), better GPS (HR 0.61, 95% CI 0.46–0.81, P = 0.001), and no bone metastasis (HR 0.31, 95% CI 0.15–0.68, P = 0.003). There was a trend for PPS in favor of the docetaxel group compared with patients who refused docetaxel treatment in the BSC group (adjusted HR 0.61, 95% CI 0.29–1.29, P = 0.20). Docetaxel treatment may have prolonged survival in platinum‐refractory patients with AEC.     

Improved prognosis with additional medium‐dose VP16 to CY/TBI in allogeneic transplantation for high risk ALL in adults

Allogeneic hematopoietic stem cell transplantation (HSCT) with the conventional cyclophosphamide and total body irradiation (CY/TBI) regimen is an essential therapeutic strategy for acute lymphoblastic leukemia (ALL) in adults. Medium‐dose etoposide (VP16, 30‐40 mg/kg) can be added to intensify this CY/TBI regimen and reduce relapse; however, differences in prognosis between the VP16/CY/TBI and CY/TBI regimens have not yet been fully analyzed. We conducted a retrospective cohort study using a Japanese transplant registry database to compare the prognosis between the VP16/CY/TBI (VP16, total 30‐40 mg/kg) (N = 376) and CY/TBI (N = 1178) regimens in adult patients with ALL transplanted at complete remission (CR) between January 1, 2000 and December 31, 2014. Our analyses indicated that VP16/CY/TBI significantly reduced relapse compared with CY/TBI (risk ratio, 0.75; 95% confidence interval [CI], 0.56‐1.00; P = .05) with a corresponding improvement in leukemia‐free survival (hazard ratio [HR], 0.76; 95%CI, 0.62‐0.93; P = .01), particularly in patients transplanted at CR1 with advanced‐risk (positive minimal residual disease, presence of poor‐risk cytogenetics, or an initial elevated leukocyte count) (HR, 0.75; 95%CI, 0.56‐1.00; P = .05) or those transplanted beyond CR2 (HR, 0.58; 95%CI, 0.39‐0.88; P = .01). The addition of VP16 did not increase post‐transplant complications or nonrelapse mortality (HR, 0.88; 95%CI, 0.65‐1.18; P = .38). This study is the first to reveal the efficacy of the addition of medium‐dose VP16 to CY/TBI in high‐risk ALL. To establish new myeloablative conditioning regimens including VP16, a large‐scale prospective study is necessary.     

Risk Factors for Early Failure of Arteriovenous Vascular Access Among Patients With Type 2 Diabetes Mellitus

The aim of the study was to identify the potential risk factors for early arteriovenous access failure in a diabetic population. The data of 223 end‐stage renal disease (ESRD) patients with type 2 diabetes who had an arteriovenous fistula (AVF) or arteriovenous graft (AVG) placed as their initial vascular accesses were retrospectively reviewed. The association between clinical factors and risk for early failure was then analyzed. In multivariate analysis, the predictors associated with early failure were female gender (odds ratio (95% confidence interval): 2.52 (1.32–4.81); P = 0.005), AVF with prior peritoneal dialysis (3.26 (1.05‐10.11); P = 0.039), and lower hemoglobin level (P = 0.015). The results of significant predictors in the AVF group remained similar to the entire study population. In conclusion, there was an association of female gender, AVF with prior peritoneal dialysis and lower hemoglobin level with early arteriovenous access failure in a diabetic ESRD population.     

Comparison of single‐ versus two‐stent techniques in treatment of unprotected left main coronary bifurcation disease

Background : This study sought to compare 3‐year outcomes of single‐ versus two‐stent techniques in patients with distal unprotected left main coronary artery (LMCA) disease treated with drug‐eluting stents (DES). Methods and Results : A total of 392 patients with distal unprotected LMCA disease who underwent DES implantation with single‐ (n = 234) or two‐ (n = 158) stent techniques were evaluated. The primary end point was major adverse cardiac events (MACE), defined as the composite of death, myocardial infarction (MI), and target lesion revascularization (TLR). The two‐stent group was more likely to have extensive coronary artery stenosis. After adjustment with weighted Cox model using the inverse probability of treatment weighting, the 3‐year risk of death was similar in the single‐ and two‐stent groups (hazard ratio [HR], 0.77, 95% confidence interval [CI], 0.28–2.13, P = 0.62). However, the 3‐year risks of MI (HR, 0.38, 95% CI, 0.19–0.78, P = 0.008), TLR (HR, 0.16, 95% CI, 0.05–0.57, P = 0.005), and MACE (HR, 0.89, 95% CI, 0.22–0.67, P = 0.0007) were significantly lower in the single‐stent group. Conclusion : Compared with the two‐stent technique, the single‐stent technique showed more favorable long‐term clinical outcomes in patients with distal unprotected LMCA disease who received DES. © 2011 Wiley‐Liss, Inc.     

Distal Radial Artery Pressures Predict Angiographic Result and Short‐Term Patency Outcome in Hemodialysis Patients With Juxta‐Anastomotic Inflow Stenosis of Radiocephalic Fistula Undergoing Transradial Angioplasty

Distal radial artery pressure (RAP) was observed to be reduced after transradial percutaneous transluminal angioplasty (PTA) on the juxta‐anastomotic venous stenosis of radiocephalic arteriovenous fistula (RCAVF). Distal RAPs are easily obtained from a pressure transducer connected with an introducer retrograde inserted into distal radial artery. The clinical role of distal RAP in the setting of transradial PTA remains unknown. This prospective and observational study aimed to explore the relationship between distal RAPs and clinical outcomes. This study recruited hemodialysis patients with RCAVF juxta‐anastomotic venous stenosis undergoing transradial PTA. RAP‐related variables and procedural data before PTA (pre‐PTA) and after PTA (post‐PTA) were analyzed. The study endpoint was dysfunction‐driven re‐PTA during the 1‐year follow‐up. Overall, 73 PTAs significantly reduced the mean of systolic RAPs from 159.6 ± 41.4 to 108.4 ± 41.5 mm Hg; P < 0.0001. Post‐PTA systolic RAP was associated with angiographic outcome (P = 0.004) and unassisted patency at 3 months (P = 0.036), but not at 6, 9, or 12 months (P > 0.05). The group with angiographically successful PTAs had a significantly lower mean of post‐PTA systolic RAPs compared with that with unsuccessful PTAs (98.4 ± 35.4 vs. 128.7 ± 46.1 mm Hg; P = 0.003). The post‐PTA systolic RAP may be seen as a predictor for 3‐month unassisted patency (AUC = 0.669; P = 0.048). In conclusion, this study provides the RAP profile to help guide transradial PTA on RCAVF juxta‐anastomotic venous stenosis and predict 3‐month unassisted patency in a hemodynamic manner.     

Nuclear magnetic resonance‐based metabolomics identifies phenylalanine as a novel predictor of incident heart failure hospitalisation: results from PROSPER and FINRISK 1997

Aims

We investigated the association between quantified metabolite, lipid and lipoprotein measures and incident heart failure hospitalisation (HFH) in the elderly, and examined whether circulating metabolic measures improve HFH prediction.

Methods and results

Overall, 80 metabolic measures from the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) trial were measured by proton nuclear magnetic resonance spectroscopy (n = 5341; 182 HFH events during 2.7‐year follow‐up). We repeated the work in FINRISK 1997 (n = 7330; 133 HFH events during 5‐year follow‐up). In PROSPER, the circulating concentrations of 13 metabolic measures were found to be significantly different in those who were later hospitalised for heart failure after correction for multiple comparisons. These included creatinine, phenylalanine, glycoprotein acetyls, 3‐hydroxybutyrate, and various high‐density lipoprotein measures. In Cox models, two metabolites were associated with risk of HFH after adjustment for clinical risk factors and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP): phenylalanine [hazard ratio (HR) 1.29, 95% confidence interval (CI) 1.10–1.53; P = 0.002] and acetate (HR 0.81, 95% CI 0.68–0.98; P = 0.026). Both were retained in the final model after backward elimination. Compared to a model with established risk factors and NT‐proBNP, this model did not improve the C‐index but did improve the overall continuous net reclassification index (NRI 0.21; 95% CI 0.06–0.35; P = 0.007) due to improvement in classification of non‐cases (NRI 0.14; 95% CI 0.12–0.17; P < 0.001). Phenylalanine was replicated as a predictor of HFH in FINRISK 1997 (HR 1.23, 95% CI 1.03–1.48; P = 0.023).

Conclusion

Our findings identify phenylalanine as a novel predictor of incident HFH, although prediction gains are low. Further mechanistic studies appear warranted.     

The impact of E‐cadherin expression on the prognosis of esophageal cancer: a meta‐analysis

E‐cadherin is a 120‐KD transmembrane calcium‐dependent cell adhesion protein that has been demonstrated drownregulated in a large amount of invasive tumors. However, its effect on the prognosis of esophageal cancer (EC) remains controversial. All the relevant English articles that reported survival data or clinicopathological parameters were enrolled in this meta‐analysis. A total of 24 studies, including 2691 cases, were included in this study. Twelve studies containing 1669 cases were enrolled to synthesize with hazard ratio (HR) and its 95% confidence interval (CI). The pooled HR for all 12 studies enrolled in this meta‐analysis was 1.33 (95% CI 1.16–1.52; z = 3.99, P = 0.00). When the study measured by enzyme‐linked immunosorbent assay is excluded, the pooled HR‐evaluated E‐cadherin to reduce the expression in EC, and in esophageal squamous cell carcinoma was 1.39 (95% CI 1.22–1.58; z = 5.08, P = 0.00) and 1.38 (95% CI 1.21–1.56; z = 4.87, P = 0.00), respectively. The risk of reduced E‐cadherin expression on poor differentiation degree was 1.636 (95% CI 1.33–2.02). The pooled odds ratio of reduced E‐cadherin expression on deeper tumor invasion, lymph node metastasis, and higher clinical stage were 2.63 (95% CI 1.75–3.94), 1.77 (95% CI 1.06 ?2.97), and 3.39 (95% CI 1.85–6.23). Reduced E‐cadherin expression detected by immunohistochemistry could be a valid prognostic marker in patients with EC, especially in patients with esophageal squamous cell carcinoma. Reduced E‐cadherin expression is significantly associated with poorer differentiation degree.     

IL‐28B polymorphisms and the response to antiviral therapy in HCV genotype 2 and 3 varies by ethnicity: a meta‐analysis

Studies of IL‐28B genotype in patients with hepatitis C virus (HCV) genotype 2/3 infection have yielded conflicting results. The aim of this meta‐analysis was to obtain a pooled odds ratio (OR) of the impact of IL‐28B genotype on achieving sustained virologic response (SVR) in patients with HCV genotype 2/3 infection treated with pegIFN and ribavirin. A meta‐analysis with a random effects model was performed, and study heterogeneity and publication bias were assessed. Forty‐three percent of the Caucasians (11 studies) and 86% of Asians (five studies) had the favourable IL‐28B genotype. In Caucasians, the pooled OR of SVR with the favourable IL‐28B genotype was 1.36 (95%CI: 0.98–1.88, P = 0.07) in all patients and 1.55 (95%CI: 1.10–2.18, P = 0.01) in patients treated with pegIFN and ribavirin for ≥24 weeks. In Asians, the pooled OR of SVR in patients with the favourable IL‐28B genotype was 1.99 (95%CI: 0.94–4.25, P = 0.07). The favourable IL‐28B genotype was also significantly associated with rapid virologic response (RVR) in both groups (Caucasians: OR: 1.82, 95%CI: 1.12–2.96, P = 0.02; Asians: 2.39, 95%CI: 1.39–4.11, P = 0.002), as well as the likelihood of an SVR in a subgroup of 350 Caucasian patients without an RVR (OR: 3.29, 95%CI: 1.67–6.51, P = 0.001). The favourable IL‐28B genotype is a statistically significant predictor of SVR and RVR in Caucasian patients treated with pegIFN and ribavirin for 24 weeks. In contrast, the favourable IL‐28B genotype is associated with RVR, but not SVR in Asian HCV genotype 2 patients.     

Percutaneous radiofrequency ablation as first‐line treatment for small hepatocellular carcinoma: Results and prognostic factors on long‐term follow up

Background and Aims: We evaluated the prognosis and associated factors in patients with small hepatocellular carcinoma (HCC; up to 3 nodules, each up to 3cm in diameter) treated with percutaneous radiofrequency ablation (RFA) as first‐line treatment. Methods: Eighty‐eight consecutive patients who underwent percutaneous RFA as first‐line treatment were enrolled, among whom 70 who had hypervascular HCC nodules which were treated by a combination of transcatheter arterial chemoembolization and RFA. RFA was repeated until an ablative margin was obtained. Results: The rate of local tumor progression at 1 and 3 years was 4.8% and 4.8%, respectively. The rate of overall survival at 3 and 5 years was 83.0% and 70.0%, and the rate of disease‐free survival at 3 and 5 years was 34.0% and 24.0%, respectively. On multivariate analysis, age (< 70 years; hazard ratio [HR] = 2.341, 95% confidence interval [CI] = 1.101–4.977, P = 0.027) and indocyanine green retention rate at 15 min (< 15%; HR = 3.621, 95% CI = 1.086–12.079, P = 0.036) were statistically significant determinants of overall survival, while tumor number (solitary, HR = 2.465, 95% CI = 1.170–5.191, P = 0.018) was identified for disease‐free survival. Overall survival of patients with early recurrence after RFA was significantly worse than that of patients with late recurrence. Tumor size was the only independent risk factor of early recurrence after RFA of HCC (tumor size > 2 cm; risk ratio [RR] = 4.629, 95% CI = 1.241–17.241, P = 0.023). Conclusion: Percutaneous RFA under the protocol reported here has the potential to provide local tumor control for small HCC. In addition to host factors, time interval from RFA to recurrence was an important determinant of prognosis.     

Comparison of long‐term outcomes of drug‐eluting stents and bare metal stents for saphenous vein graft stenosis

Objective : Our aim was to compare the long‐term outcomes between drug‐eluting stents and bare‐metal stents for saphenous vein graft stenosis. Background : The ideal type of stent to treat saphenous vein graft stenosis has not been clearly established. Short‐term randomized controlled trial results comparing drug‐eluting stents with bare‐metal stents for saphenous vein graft stenosis are conflicting, intermediate‐term retrospective studies and meta‐analyses at two years suggest no difference in outcomes, and there are no long term follow‐up studies. The need for long term follow‐up data has become emerged with concern over late stent thrombosis. Methods : 246 saphenous vein graft patients undergoing stenting from August 2002–December 2008 were studied. Overall survival and event‐free survival were compared by Kaplan‐Meier method. Hazard ratios (HR) were calculated by Cox‐proportional hazards models. Results : We treated 133 patients with DES (median follow‐up four years) and 113 patients with BMS (median follow‐up four years) for SVG stenosis. Overall survival (77.0% ± 3.9% vs. 70.6% ± 4.6%, log‐rank P = 0.60) and MACE‐free survival (57.5% ± 4.6% vs. 56.8% ± 4.9, log‐rank P = 0.70) were not significantly different between the DES and BMS groups. Although BMS was associated with increased risk of target lesion revascularization (TLR) (freedom from TLR 85.2% ± 3.5% vs. 90.0% ± 3.0%, HR 2.07, 95% CI 0.97–4.42, log‐rank P = 0.05), there was no significant difference in the freedom from myocardial infarction (86.7% ± 3.3% vs. 88.7% ± 3.2%, log‐rank P = 0.39) or target vessel revascularization (77.1% ± 4.2% vs. 76.1% ± 4.2%, log‐rank P = 0.33) between the two groups. Conclusions : Although mortality is not statistically different between DES and BMS for SVG stenosis, BMS is associated with increased risk of revascularization, thus suggesting the superiority of DES over BMS in the long term. © 2011 Wiley Periodicals, Inc.     

Rates of myocardial infarction and stroke in patients initiating treatment with SGLT2‐inhibitors versus other glucose‐lowering agents in real‐world clinical practice: Results from the CVD‐REAL study

The multinational, observational CVD‐REAL study recently showed that initiation of sodium‐glucose co‐transporter‐2 inhibitors (SGLT‐2i) was associated with significantly lower rates of death and heart failure vs other glucose‐lowering drugs (oGLDs). This sub‐analysis of the CVD‐REAL study sought to determine the association between initiation of SGLT‐2i vs oGLDs and rates of myocardial infarction (MI) and stroke. Medical records, claims and national registers from the USA, Sweden, Norway and Denmark were used to identify patients with T2D who newly initiated treatment with SGLT‐2i (canagliflozin, dapagliflozin or empagliflozin) or oGLDs. A non‐parsimonious propensity score was developed within each country to predict initiation of SGLT‐2i, and patients were matched 1:1 in the treatment groups. Pooled hazard ratios (HRs) and 95% CIs were generated using Cox regression models. Overall, 205 160 patients were included. In the intent‐to‐treat analysis, over 188 551 and 188 678 person‐years of follow‐up (MI and stroke, respectively), there were 1077 MI and 968 stroke events. Initiation of SGLT‐2i vs oGLD was associated with a modestly lower risk of MI and stroke (MI: HR, 0.85; 95%CI, 0.72‐1.00; P = .05; Stroke: HR, 0.83; 95% CI, 0.71‐0.97; P = .02). These findings complement the results of the cardiovascular outcomes trials, and offer additional reassurance with regard to the cardiovascular effects of SGLT‐2i, specifically as it relates to ischaemic events.     

Long‐term clinical outcomes of successful versus unsuccessful revascularization with drug‐eluting stents for true chronic total occlusion

Objectives: The aims of this study were to investigate the long‐term clinical outcomes of patients with successful versus unsuccessful revascularization with drug‐eluting stents (DES) for chronic total occlusion (CTO). Background: The benefits of successful revascularization of CTO remain unclear. Methods: Consecutive patients (n = 333) with “true” CTO, defined as Thrombolysis In Myocardial Infarction (TIMI) flow grade 0 on angiography and duration ≥3 months, were divided into two groups, those with successful (CTO success group, n = 251) and unsuccessful (CTO failure group, n = 82) revascularization with DES for CTO lesions. The primary endpoint was defined as major adverse cardiac events (MACE) the composite of death, Q‐wave myocardial infarction (MI), or target vessel revascularization (TVR). Results: The CTO success group was significantly younger, with a higher involvement of LAD, and lower incidences of renal failure, previous myocardial infarction, and previous coronary intervention than the CTO failure group. After a median follow up of 1,317 days (interquartile range, 1,059–1,590 days), there were no significant between‐group differences in rate of MACE, both after crude analysis (9.4% vs. 11.8%, log‐rank P = 0.16) and after adjustment (HR 1.17; 95% CI 0.47–2.88, P = 0.53). On multivariate analysis, major predictors of MACE were left ventricle ejection fraction (LVEF) <40% (HR 3.14; 95% CI 1.39–7.09, P = 0.005) and multiple CTO (HR 2.38; 95% CI 1.01–5.71, P = 0.049). Conclusions: Long‐term clinical outcomes were similar in the CTO success and failure groups. Multiple CTOs and LVEF <40% in CTO patients were independent predictors of MACE. © 2011 Wiley‐Liss, Inc.     

Comparative long-term efficacy and safety of drug-eluting stent versus coronary artery bypass grafting in ostial left main coronary artery disease: analysis of the MAIN-COMPARE registry

Background : To date, drug‐eluting stent (DES) implantation has not been compared with coronary artery bypass grafting (CABG) for ostial left main coronary artery (LMCA) lesions. Methods : Of the 263 patients in the MAIN‐COMPARE registry with ostial LMCA stenosis, 123 were treated with percutaneous coronary intervention (PCI) with DES and 140 with CABG. We compared their 5‐year overall survival, composite outcomes of death, Q‐wave myocardial infarction (MI) or stroke, and target vessel revascularization (TVR) rates. Results : Unadjusted analysis showed no significant differences between CABG and DES in overall survival rates (95% confidence interval (CI) for hazard ratio (HR): 0.44 to 1.77, P = 0.71), composite outcomes (death, Q‐wave MI, or stroke)‐free survival rates (95% CI for HR: 0.41–1.63, P = 0.56), and TVR‐free survival rates (95% CI for HR: 0.79–5.03, P = 0.14). Multivariate adjusted Cox regression analysis also showed no significant between‐group differences in TVR (95% CI for HR: 0.52–3.79, P = 0.49), death (95% CI for HR: 0.79–2.82, P = 0.22) and the composite of death, Q‐wave MI, or stroke (95% CI for HR: 0.65–2.57, P = 0.46). These results were sustained after propensity score adjustment and propensity score matching analysis. Conclusions : DES implantation for ostial LMCA lesions showed similar 5‐year outcomes of death, major adverse events, and TVR compared with CABG. Although meticulous adjustments decreased baseline difference between the two treatments, the absence of statistical significance could be attributable to the size of the study sample and hidden bias. © 2012 Wiley Periodicals, Inc.     

Preoperative and Intraoperative Factors for Early Failure of Native Arteriovenous Fistulas

The aim of the study was to assess the potential predictive factors for early arteriovenous fistula (AVF) failure following the fistula first initiative. We retrospectively reviewed the data of 159 end‐stage renal disease (ESRD) patients who underwent AVF creation. The preoperative factors such as demographic, comorbidity condition, laboratory parameters and medication, and intraoperative or surgical‐related factors were assessed. In multivariate logistic regression analysis, significant predictive factors of early AVF failure were female gender (odds ratio (95% confidence interval): 2.63 (1.19–5.81); P = 0.017), higher body mass index (P = 0.038), and lower hemoglobin level (P = 0.048), while adjusting for preoperative factors or all factors. For adjusting of intraoperative factors, reduced venous diameter (P = 0.056) tended to be associated with early AVF failure. In conclusion, female gender, higher body mass index and lower hemoglobin level predicted the occurrence of early AVF failure in ESRD patients.