Vascular endothelial growth factor-165 gene therapy promotes cardiomyogenesis in reperfused myocardial infarction

BACKGROUND: Vascular endothelial growth factor (VEGF)-165 promotes cardiomyogenesis in chronic myocardial ischemia and nonreperfused myocardial infarction (MI). It is unknown whether this effect is present in reperfused MI. We sought to investigate the effect of VEGF-165 gene therapy on cardiomyogenesis after reperfused MI. METHODS AND RESULTS: Twenty-four Yucatan minipigs underwent thoracotomy and a vascular clamp was placed in the left circumflex artery. Reperfusion was reestablished after 90 minutes, and VEGF-165 gene therapy or placebo was administered. A replication-deficient recombinant human adenovirus serotype 5 was used for gene transfer (Ad5-VEGF165). The same viral vector devoid of VEGF gene (Ad5-beta-galactosidase) was used as placebo. Two administration routes were tested, intramyocardial (IM) injection and circumflex intracoronary (IC) infusion. The pigs were assigned to one of the following groups: IM Ad5-VEGF165 (n = 6), IM Ad5-betaGal (n = 6), IC Ad5-VEGF165 (n = 6), and IC Ad5-betaGal (n = 6). All pigs received 5-bromo-2'-deoxyuridine (BrdU) 250 mg IV twice a week to label cells undergoing DNA replication. The hearts were explanted at 4 weeks. BrdU-labeled cardiomyocytes in the peri-infarct area were counted by a pathologist blinded to group assignment. The number of BrdU-labeled cardiomyocytes per million cells was 4-fold higher in the group receiving IM VEGF-165 (64 +/- 11.4) vs. IM placebo (16 +/- 10.6), P = 0.034. No difference in infarct size or ventricular function was observed between the groups. CONCLUSIONS: IM VEGF-165 gene therapy promotes cardiomyogenesis in reperfused MI. However, no benefit in infarct size or cardiac function was observed at 4 weeks. The origin of these cells remains unknown and needs to be determined.     

Cutting balloon versus conventional balloon angioplasty for the treatment of in-stent restenosis: results of the restenosis cutting balloon evaluation trial (RESCUT)

OBJECTIVES: The aim of this trial was to compare cutting balloon angioplasty (CBA) with conventional balloon angioplasty (i.e., percutaneous transluminal coronary angioplasty [PTCA]) for the treatment of patients with coronary in-stent restenosis (ISR). BACKGROUND: Retrospective studies suggest CBA might be superior to conventional PTCA in the treatment of ISR. METHODS: The Restenosis Cutting Balloon Evaluation Trial (RESCUT) is a multicenter, randomized, prospective European trial including 428 patients with all types of ISR (e.g., focal, multifocal, diffuse, proliferative). RESULTS: In both groups, the majority of ISR lesions were shorter than 20 mm. The length of restenotic stents was similar (CBA: 18.6 +/- 9.7 mm; PTCA: 18.3 +/- 8.7 mm). The number of balloons used to treat ISR was lower in the CBA group: only one balloon was used in 82.3% of CBA cases, compared with 75% of PTCA procedures (p = 0.03). Balloon slippage was less frequent in the CBA group (CBA 6.5%, PTCA 25%; p < 0.01). There was a trend toward a lower need for additional stenting in the CBA group (CBA 3.9%, PTCA 8.0%; p = 0.07). At seven-month angiographic follow-up, the binary restenosis rate was not different between the groups (CBA 29.8%, PTCA 31.4%; p = 0.82), with a similar pattern of recurrent restenosis. Clinical events at seven months were also similar. CONCLUSIONS: Cutting balloon angioplasty did not reduce recurrent ISR and major adverse cardiac events, as compared with conventional PTCA. However, CBA was associated with some procedural advantages, such as use of fewer balloons, less requirement for additional stenting, and a lower incidence of balloon slippage.     

Induction of neutralizing antibodies and partial protection from viral challenge in Macaca fascicularis immunized with recombinant dengue 4 virus envelope glycoprotein expressed in Pichia pastoris

A recombinant vaccine that expresses the envelope (E) gene of dengue virus type 4 was tested for immunogenicity and protection in Macaca fascicularis. One hundred micrograms of semipurified recombinant E protein (E4rec) expressed in Pichia pastoris was used to immunize three animals. Neutralizing antibodies to dengue 4 virus with a titer of 1:30 were detected in all immunized monkeys prior to challenge. Animals were challenged with 10(5) plaque-forming units of dengue 4 virus. One vaccine-immunized monkey was protected from viremia, while the other two were partially protected. Monkeys immunized with E4rec elicited the highest neutralizing antibody titers (P < 0.05) ranging from 1:85 to 1:640 at day 30. In both immunized and control animals, the longest duration of viremia correlated with earliest and highest level of IgM antibody to dengue virus. The vaccinated animals showed anamnestic antibody responses upon virus challenge, indicating successful priming by the recombinant vaccine. Our results suggest that E4rec expressed in P. pastoris can provide partial protection against viremia. However, the results were not effective enough to use it as a vaccine candidate. Further work is required to improve the quality of the immunogen.     

Does the specific intravascular ultrasound criterion used to optimize stent expansion have an impact on the probability of stent restenosis?

Intravascular ultrasound (IVUS) imaging has been used to optimize stent implantation in coronary arteries, but the criteria used were chosen on an empiric basis. The aim of this study was to determine whether any of these criteria have an independent role in predicting the probability of freedom from restenosis. The study population consisted of 425 patients (496 lesions) who underwent angiographically successful IVUS-guided stenting. Five IVUS criteria were studied: (1) intrastent minimal lumen cross-sectional area (ISMLCSA) > or =9 mm2; (2) ISMLCSA (> or =9 mm2 and > or =80% of average reference lumen cross-sectional area [CSA]); (3) ISMLCSA > or =90% of average reference lumen CSA; (4) ISMLCSA > or =90% of distal reference lumen CSA; and (5) ISMLCSA > or =55% of average reference vessel CSA. These criteria were met in 33%, 29%, 68%, 82%, and 69% of lesions, respectively. Angiographic follow-up was performed in 335 of 421 eligible patients (80%) at 5.3 +/- 2.7 months. An absolute ISMLCSA > or =9 mm2 was associated with the lowest restenosis, but this criterion was primarily achieved in large vessels. The only criterion that was associated with higher probability of freedom from restenosis independently from vessel size was an ISMLCSA > or =55% of average reference vessel CSA. Therefore, when IVUS is used to guide stent implantation an effort should be made to achieve the largest lumen safely possible. An ISMLCSA > or =55% of the average reference vessel CSA seems to be the most appropriate criterion in terms of frequency of achievement and in terms of increasing the probability of freedom from restenosis.     

Survival following renal artery stent revascularization: four-year follow-up

To evaluate survival following renal artery stenting, 72 consecutive patients (Mean age 69 +/-10 years, 72% African-American) were retrospectively evaluated over a 4-year period. Complete follow-up was available in 97% patients (70/72). Twelve patients (12/70 = 17%) died; 2 procedure-related (renal stent = 1, coronary stent = 1), one cancer-related and 9 cardiac. The overall survival at a mean follow-up of 31 +/- 13 months was 83%. Eight patients (8/70 = 11%) were eligible for 1 year, 25/70 (36%) for 2 year, 16/70 (23%) for 3 year, 21/70 (30%) for 4 years (or longer) follow up. Five patients died within 1 year, three during the second year, three during the third year and 1 patient after the forth year. Abnormal baseline serum creatinine, male gender, bilateral renal artery stenosis and systolic dysfunction were associated with statistically significant lower survival.     

Cutting balloon angioplasty for the treatment of in-stent restenosis: a matched comparison with rotational atherectomy, additional stent implantation and balloon angioplasty

OBJECTIVES: The purpose of the study was to determine whether cutting balloon angioplasty (CBA) has advantages over other modalities in treatment of in-stent restenosis (ISR). BACKGROUND: Controversies exist regarding optimal treatment for ISR. Recently, CBA emerged as a tool in management of ISR. METHODS: A total of 648 lesions treated for ISR were divided into four groups according to the treatment strategy: CBA, rotational atherectomy (ROTA), additional stenting (STENT), and percutaneous transluminal coronary angioplasty (PTCA). Following the matching process, 258 lesions were entered into the analysis. RESULTS: Baseline clinical and angiographic characteristics were similar among the groups (p = NS). Acute lumen gain was significantly higher in the STENT group (2.12 +/- 0.7 mm), whereas in the CBA group the gain was similar to one achieved following ROTA and following PTCA (1.70 +/- 0.6 vs. 1.79 +/- 0.5 mm and 1.56 +/- 0.7 mm, respectively; p = NS). The lumen loss at follow-up was lower for the CBA versus ROTA and versus STENT (0.63 +/- 0.6 vs. 1.30 +/- 0.8 mm and 1.36 +/- 0.8 mm, respectively; p < 0.0001), yielding a lower recurrent restenosis rate (20% vs. 35.9% and 41.4%, respectively; p < 0.05). By multivariate analysis, CBA (odds ratio [OR] = 0.17; confidence interval [CI], 0.06 to 0.51; p = 0.001) and diffuse restenosis type at baseline (OR = 2.07; CI, 1.15 to 3.71; p = 0.02) were identified as predictors of target lesion revascularization. CONCLUSIONS: We conclude that CBA is a safe and efficient technique for treatment of ISR, with immediate results similar to atheroablation and better clinical and angiographic outcomes at follow-up. This approach might be implemented as a viable option in management of focal ISR and to prepare diffuse ISR for brachytherapy treatment.     

Environmental and anthropometric factors associated with childhood arterial hypertension

Childhood obesity is considered pandemic with significant social and economical costs because of its high morbidity and mortality. To evaluate the association between biological and environmental factors and infantile arterial hypertension (AH), a cross-sectional study was performed with 701 children, ranging from 5 to 9 years old, from Feira de Santana, BA. The arterial pressure was measured following the criteria of the Update on the 1987 Task Force Report on High Blood Pressure in Children and Adolescents. Overweight and obesity were defined as body-mass index equal or above the 85th and the 95th percentiles for age and gender, respectively. Interviews with the children's responsible were used to determine the role of gender, ethnic group, age, familiar history of AH, and type of school. Overweight (OR= 4.49; rho= 0.04), obesity (OR= 13.05; rho= 0.000) and studying at private school (OR= 1.93; r= 0.13) were observed as predictive and independent factors associated with hypertension. Therefore, biological and environmental factors seem to be involved on the genesis of AH in children.     

Indications for operative fixation of distal radius fractures - a review of the evidence

Operative fixation of distal radius fractures is one of the most commonly performed orthopedic procedures. However, there remains little consensus on the indications for operative versus nonoperative treatment of these injuries. The American Academy of Orthopaedic Surgeons has recently published clinical practice guidelines to help guide management of these injuries. The purpose of this paper is to review the biomechanical and clinical retrospective and prospective data pertinent to the indications for operative management of distal radius fractures. Conflicting data exists as to the optimal management of these injuries, especially in patients over the age of 55. Although there is some evidence to support operative fixation of distal radius fractures, better longterm, prospective, randomized studies with validated patient outcome measures are needed to definitively establish the optimal method of treatment for these injuries.     

High Blood Pressure in Overweight and Obese Youth: Implications for Screening

In the absence of evidence‐based guidelines for high blood pressure screening in asymptomatic youth, a reasonable strategy is to screen those who are at high risk. The present study aimed to identify optimal body mass index (BMI) thresholds as a marker for high‐risk youth to predict hypertension prevalence. In a cross‐sectional study, youth aged 6 to 17 years (n=237,248) enrolled in an integrated prepaid health plan in 2007 to 2009 were classified according to their BMI and hypertension status. In moderately and extremely obese youth, the prevalence of hypertension was 3.8% and 9.2%, respectively, compared with 0.9% in normal weight youth. The adjusted prevalence ratios (95% confidence intervals) of hypertension for normal weight, overweight, moderate obesity, and extreme obesity were 1.00 (Reference), 2.27 (2.08–2.47), 4.43 (4.10–4.79), and 10.76 (9.99–11.59), respectively. The prevalence of hypertension was best predicted by a BMI‐for‐age ≥94th percentile. These results suggest that all obese youth should be screened for hypertension.