NC100100, a new echo contrast agent for the assessment of myocardial perfusion--safety and comparison with technetium-99m sestamibi single-photon emission computed tomography in a randomized multicenter study

BACKGROUND AND HYPOTHESIS: Myocardial contrast echocardiography using second-generation agents has been proposed to study myocardial perfusion. A placebo-controlled, multicenter trial was conducted to evaluate the safety, optimal dose, and imaging mode for NC100100, a novel intravenous second-generation echo contrast agent, and to compare this technique with technetium-99m sestamibi (MIBI) single-photon emission computed tomography (SPECT). METHODS: In a placebo-controlled, multicenter trial, 203 patients with myocardial infarction > 5 days and < 1 year previously underwent rest SPECT and MCE. Fundamental and harmonic imaging modes combined with continuous and electrocardiogram-- (ECG) triggered intermittent imaging were used. Six dose groups (0.030, 0.100, and 0.300 microliter particles/kg body weight for fundamental imaging; and 0.006, 0.030, and 0.150 microliter particles/kg body weight for harmonic imaging) were tested. A saline group was also included. Safety was followed for 72 h after contrast injection. Myocardial perfusion by MCE was compared with myocardial rest perfusion imaging using MIBI as a tracer. RESULTS: NC100100 was well tolerated. No serious adverse events or deaths occurred. No clinically relevant changes in vital signs, laboratory parameters, and ECG recordings were noted. There was no significant difference between adverse events in the NC100100 (25.7%) and in the placebo group (17.9%, p = 0.3). Intermittent harmonic imaging using the intermediate dose was superior to all other modalities, allowing the assessment of perfusion in 76% of all segments. Eighty segments (96%) with normal perfusion by SPECT imaging also showed myocardial perfusion with MCE. However, a substantial percentage of segments (61-80%) with perfusion defects by SPECT imaging also showed opacification by MCE. This resulted in an overall agreement of 66-81% and a high specificity (80-96%), but in low sensitivity (20-39%) of MCE for the detection of perfusion defects. CONCLUSION: NC100100 is safe in patients with myocardial infarction. Intermittent harmonic imaging with a dose of 0.03 microliter particles/kg body weight can be proposed as the best imaging protocol. Myocardial contrast echocardiography with NC 100100 provides perfusion information in approximately 76% of segments and results in myocardial opacification in the vast majority of segments with normal perfusion as assessed by SPECT. Although the discrepancies between MCE and SPECT with regard to the definition of perfusion defects requires further investigation, MCE with NC 100100 is a promising technique for the noninvasive assessment of myocardial perfusion.     

Oral active vitamin D is associated with improved survival in hemodialysis patients

Injection of active vitamin D is associated with better survival of patients receiving chronic hemodialysis. Since in many countries oral active vitamin D administration is the most common form of treatment for secondary hyperparathyroidism we determined the survival benefit of oral active vitamin D in hemodialysis patients from six Latin America countries (FME Register as part of the CORES study) followed for a median of 16 months. Time-dependent Cox regression models, after adjustment for potential confounders, showed that the 7,203 patients who received oral active vitamin D had significant reductions in overall, cardiovascular, infectious and neoplastic mortality compared to the 8,801 patients that had not received vitamin D. Stratified analyses found a survival advantage in the group that had received oral active vitamin D in 36 of the 37 strata studied including that with the highest levels of serum calcium, phosphorus and parathyroid hormone. The survival benefit of oral active vitamin D was seen in those patients receiving mean daily doses of less than 1 microg with the highest reduction associated with the lowest dose. Our study shows that hemodialysis patients receiving oral active vitamin D had a survival advantage inversely related to the vitamin dose.     

Female Liver Transplant Recipients with the Same GFR as Male Recipients Have Lower MELD Scores—A Systematic Bias

Women have lower glomerular filtration (GFR) than men for the same serum creatinine (Cr) value, not accounted for in model for end-stage liver disease (MELD). We compare male/female Cr, GFR (using MDRD formula) and respective MELD scores in 403 Cr measurements using standard (sCr), O'Leary modified (mCr) and Compensated (cCr) Jaffe and Enzymatic (eCr) in 158 liver disease patients, mCr in 208 liver transplantation (LT) candidates, and EDTA-Cr(51)-GFR in 38 other candidates for LT; considering each female as male, a 'corrected' Cr was derived. MELD scores were calculated for measured and "corrected" Cr in females. Median Cr and GFR in females were lower than males (p < 0.05). Both MDRD and EDTA-Cr(51) GFR were lower in females than males, despite lower Cr values. In females, each MELD score was lower than the corresponding MELD-corrected Cr (p < 0.001) with > or =three-point difference in liver disease patients: 25%[sCr]; 23%[mCr]; 11%[eCr]; and 14%[cCr]. In 65% of female LT candidates, two- or three-point difference was found. Females with liver disease have lower GFR than males for the same Cr value; correcting Cr increases MELD score by two or three points in 65% of female LT candidates. MELD score adjustment in females would ensure equal LT priority by gender.     

Tricuspid valve repair using autologous pericardium annuloplasty in adults

Uncorrected functional tricuspid regurgitation can lead to long-term morbidity and mortality. To evaluate our results using autologous pericardium annuloplasty to treat tricuspid regurgitation, we retrospectively reviewed 59 consecutive adult patients aged 19 years to 83 years (58.7 +/- 15.5 years) who underwent tricuspid valve annuloplasty between 2000 and 2003. Concomitant procedures consisted of mitral valve surgery in 83% of patients, aortic valve surgery in 28%, coronary bypass in 31%, and atrial-septal defect correction in 28%. Annuloplasty was performed using a strip of pericardium treated in glutaraldehyde 0.6% for 10 min. Two rows of continuous horizontal mattress Gore-Tex sutures were used to secure the pericardium to the tricuspid annulus. Follow-up was performed in 100% of the patients, and the mean follow-up was 4.4 +/- 1.2 years (range, 2.4 to 7 years). Postoperative death within 30 days occurred in 1 of 59 patients (1.6%). None of the patients required reoperation related to tricuspid regurgitation or stenosis. The actuarial survival rate was 98.4% at 7 years after operation. Echocardiography was performed in 58 of 58 surviving patients (100%). Up to 7 years postoperatively, tricuspid regurgitation was trace in 67.2% of patients, mild in 31%, and moderate in 1.8%; there was no occurrence of severe regurgitation on follow-up. Our results indicate that autologous pericardium tricuspid annuloplasty is a useful procedure in patients with moderate or severe tricuspid regurgitation. This procedure provides a durable, reproducible annuloplasty of the tricuspid valve.     

Review article: renal function assessment in cirrhosis - difficulties and alternative measurements

BACKGROUND: Renal function in patients with cirrhosis is important prognostically, both before and following liver transplantation. Its prognostic impact is reflected by the inclusion of serum creatinine in the model for end-stage liver disease score, which is now used for recipient prioritization on liver transplantation waiting lists in the USA. AIM: To review the accuracy of the surrogate markers for the assessment of renal function, i.e. glomerular filtration rate, particularly in patients with cirrhosis. METHOD: We reviewed the available literature in PubMed regarding the markers for GFR evaluation and the factors which affect their accuracy in cirrhosis. RESULTS: Although creatinine is widely available, it is an unreliable marker of glomerular filtration rate, particularly in patients with cirrhosis. Clearance of exogenous markers is considered the 'gold standard', but this methodology has many drawbacks, particularly poor applicability. Several mathematical formulae for estimated glomerular filtration rate are used to overcome some of these limitations: Cockcroft-Gault and Modification of Diet in Renal Disease formulae are the most frequently applied, but they are based on serum creatinine. CONCLUSIONS: Due to the inaccuracy of serum creatinine and its derived formulae in estimating glomerular filtration rate, alternative serum markers, such as cystatin C, and new formulae are desirable. These need formal evaluation in patients with cirrhosis so as to have a reliable surrogate of glomerular filtration rate, and to obviate many problems that are associated with using creatinine and estimated glomerular filtration rate.     

Satisfaction and compliance in hormonal contraception: the result of a multicentre clinical study on women's experience with the ethinylestradiol/norelgestromin contraceptive patch in Italy

Background  

For many women finding the right contraceptive method can be challenging and consistent and correct use over a lifetime is difficult. Even remembering to take a birth control pill every day can be a challenge. The primary objective of this study was to evaluate women's experience with a weekly ethinylestradiol/norelgestromin contraceptive patch (EE/NGMN patch), given new technologies recently developed in hormonal contraception to increase women's options in avoiding daily dosing.