Video-assisted cardioscopy for intraventricular repair in congenital heart disease

BACKGROUND: Video-assisted thoracoscopic surgical techniques have been widely adopted as a means to reduce surgical trauma. By adapting pediatric thoracoscopic instrumentation, we have developed a technique for video-assisted cardioscopy (VAC). We report our experience and describe the technical feasibility of VAC. METHODS: Since June 1995, 409 consecutive patients underwent 431 intracardiac procedures (ventricular septal defect, 150; tetralogy of Fallot or double outlet right ventricle, 101; atrioventricular canal, 52; subaortic stenosis, 43; valve repair, 50; Rastelli procedure, 12; Konno or Ross Konno operation, 11; and miscellaneous, 12) using VAC at Miami Children's Hospital. Using a prospective database, we tracked outcomes and operative events to delineate the usefulness and efficacy of this technique. RESULTS: VAC provided clear and precise imaging of small or remote intracardiac structures during repair of congenital heart defects without technical complications. Procedure times and aortic cross-clamp times using VAC were not prolonged. Intraoperative images were collected for every operation, documenting each patient's cardiac anatomy before and after repair. Surgery through small incisions was facilitated. Operative mortality was 1.2% (5 of 409), and no patient required reoperation before discharge. At a mean follow-up interval of 22 months, the incidence of reoperation for residual or recurrent lesions was 1.2% (5 of 404). CONCLUSIONS: Our experience demonstrates the technical feasibility and clinical utility of routine endoscopic imaging during open heart surgery for congenital heart repair.     

Evaluation of in vivo genotoxicity induced by N‐ethyl‐N‐nitrosourea,benzo[a]pyrene,and 4‐nitroquinoline‐1‐oxide in the Pig‐a and gpt assays

The recently developed Pig‐a mutation assay is based on flow cytometric enumeration of glycosylphosphatidylinositol (GPI) anchor‐deficient red blood cells caused by a forward mutation in the Pig‐a gene. Because the assay can be conducted in nontransgenic animals and the mutations accumulate with repeat dosing, we believe that the Pig‐a assay could be integrated into repeat‐dose toxicology studies and provides an alternative to transgenic rodent (TGR) mutation assays. The capacity and characteristics of the Pig‐a assay relative to TGR mutation assays, however, are unclear. Here, using transgenic gpt delta mice, we compared the in vivo genotoxicity of single oral doses of N‐ethyl‐N‐nitrosourea (ENU, 40 mg/kg), benzo[a]pyrene (BP, 100 and 200 mg/kg), and 4‐nitroquinoline‐1‐oxide (4NQO, 50 mg/kg) in the Pig‐a (peripheral blood) and gpt (bone marrow and liver) gene mutation assays. Pig‐a assays were conducted at 2, 4, and 7 weeks after the treatment, while gpt assays were conducted on tissues collected at the 7‐week terminal sacrifice. ENU increased both Pig‐a and gpt mutant frequencies (MFs) at all sampling times, and BP increased MFs in both assays but the Pig‐a MFs peaked at 2 weeks and then decreased. Although 4NQO increased gpt MFs in the liver, only weak, nonsignificant increases (two‐ or threefold above control) were detected in the bone marrow in both the Pig‐a and the gpt assay. These findings suggest that further studies are needed to elucidate the kinetics of the Pig‐a mutation assay in order to use it as an alternative to the TGR mutation assay. Environ. Mol. Mutagen. 54:747–754, 2013. © 2013 Wiley Periodicals, Inc.     

Acarbose treatments improve arterial stiffness in patients with type 2 diabetes mellitus

Aims/Introduction: Although the improvement of postprandial hyperglycemia by an alpha‐glucosidase inhibitor (α‐GI) has been associated with a risk reduction of cardiovascular events, the relationship between postprandial hyperglycemia and arterial stiffness has not been well understood. We therefore examined whether ameliorating the postprandial state by α‐GI leads to an improvement in arterial stiffness. Materials and Methods: A total of 22 patients with type 2 diabetes mellitus were treated with acarbose. Cardio‐ankle vascular index (CAVI) as the arterial stiffness was measured by using a VaSera CAVI instrument before and 12 months after acarbose treatment. Serum high‐sensitivity C‐reactive protein (hs‐CRP), pentraxin‐3 (PTX3) and matrix metalloproteinase (MMP) ‐2, ‐9 were measured at the same time points. Furthermore, circulating peripheral blood mononuclear cells were examined for the frequencies of CD14 positive cells expressing membrane type‐1 MMP (MT1‐MMP) at the single cell level using flow cytometry. Results: After acarbose treatment, postprandial glucose and glycosylated hemoglobin (HbA_1c) were significantly decreased. Serum levels of hs‐CRP, PTX3, MMP‐2 and MMP‐9 were significantly decreased. CAVI showed a significant reduction, although the changes were not significant in blood pressure and heart rate. MT1‐MMP expression was significantly decreased by acarbose treatment. In multivariate analysis, improvement of blood glucose, decrease of PTX3 levels and MT1‐MMP expression were independent predictors of beneficial change in CAVI. Conclusions: The present study showed that the beneficial effects of acarbose on arterial stiffness are mediated by an improvement of postprandial hyperglycemia and vascular remodeling markers. In conclusion, acarbose treatment might reduce the risk of cardiovascular diseases by altering the arterial stiffness in postprandial hyperglycemic status. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2010.00079.x , 2010)     

Computational Hemodynamic Analysis in Congenital Heart Disease: Simulation of the Norwood Procedure

Hypoplastic left heart syndrome (HLHS) is a congenital heart disease which should be treated at neonate. Even now, its operation is one of the greatest challenges. However, currently there are no quantitative standards to evaluate and predict the outcome of the therapy. In this study, computational fluid dynamics (CFD) was used to estimate the performance of first stage HLHS surgery, the Norwood operation. An image data transfer system was developed to convert clinical images into three-dimensional geometry. To confirm software applicability, a validation process was carried out to eliminate any influence of numerical procedures. The velocities derived from echocardiography measurements were used as boundary conditions, and pressure waves measured by a cardiac catheter simultaneous with an electrocardiogram (ECG) were employed to validate the results of CFD simulation. Calculated results were congruent with the in vivo measurement results. The blood flow circulations were successfully simulated and the distribution of blood flow in each vessel was estimated. Time-varying energy losses (EL), local pressure and wall shear stress (WSS) were analyzed to estimate clinical treatment. The results indicated that pulsatile simulation is essential in quantitative evaluation. Computational hemodynamics may be applied in the surgical optimization for the treatment of HLHS.     

Predictive Factors for the Development or Regression of Fatty Liver in Japanese Adults

Fatty liver is commonly associated with alcohol or metabolic syndrome. We aimed to examine the longitudinal aspects of fatty liver, and clarify the independent predictors for the development or regression of fatty liver. In the present study, the clinical features of 1578 Japanese adults (1208 men and 370 women; 35 to 69 years of age) who visited our center both in 2000 and 2007–2008 were recorded and compared, including liver status diagnosed by ultrasonography. Of the 1578 participants, 217 (13.8%) showed fatty liver development, and 74 (4.7%) showed fatty liver regression. Logistic regression analysis revealed that body mass index and percentage body fat were strongly associated with the development or regression of fatty liver. Metabolic syndrome-related disorders such as serum levels of total cholesterol, triglyceride, uric acid, and fasting blood glucose were also associated with clinical course to some degree. However, the history of alcohol intake, the presence of metabolic syndrome, blood pressure, and habitual physical exercise were not independent predictors for the development or regression of fatty liver. Our present data suggest that control of body weight in men and the percentage body fat in women are particularly important for the prevention or treatment of fatty liver.     

Comparative analysis of clinical outcomes after allogeneic bone marrow transplantation versus peripheral blood stem cell transplantation from a related donor in Japanese patients

A reduced incidence of graft versus host disease (GvHD) has been documented among Japanese allogeneic bone marrow transplantation (BMT) patients, as the Japanese are genetically more homogeneous than western populations. To clarify whether this ethnic difference affects the results of allogeneic peripheral blood stem cell transplantation (PBSCT), we conducted a nationwide survey to compare clinical outcomes of allogeneic PBSCT (n = 214) and BMT (n = 295) from a human leucocyte antigen-identical-related donor in Japanese patients. The cumulative incidence of grades II-IV acute GvHD was 37.4% for PBSCT and 32.0% for BMT. The cumulative incidence of extensive chronic GvHD at 1 year was significantly higher after PBSCT than BMT (42% vs. 27%; P < 0.01). The organ involvement patterns of GvHD were different between the two groups. By multivariate analyses, the incidence of chronic GvHD was significantly increased in PBSCT, whereas the stem cell source did not affect the incidence of acute GvHD, transplant-related mortality, relapse or survival. We concluded that Japanese PBSCT patients have an increased risk of chronic GvHD compared with BMT patients, but the incidence of acute GvHD was still lower than in western populations. Thus, the choice of haematopoietic stem cell source should be considered based on data for individual ethnic populations.