Comparison of 1.0 M gadobutrol and 0.5 M gadopentate dimeglumine-enhanced MRI in 471 patients with known or suspected renal lesions: results of a multicenter, single-blind, interindividual, randomized clinical phase III trial

The purpose of this phase III clinical trial was to compare two different extracellular contrast agents, 1.0 M gadobutrol and 0.5 M gadopentate dimeglumine, for magnetic resonance imaging (MRI) in patients with known or suspected focal renal lesions. Using a multicenter, single-blind, interindividual, randomized study design, both contrast agents were compared in a total of 471 patients regarding their diagnostic accuracy, sensitivity, and specificity to correctly classify focal lesions of the kidney. To test for noninferiority the diagnostic accuracy rates for both contrast agents were compared with CT results based on a blinded reading. The average diagnostic accuracy across the three blinded readers (‘average reader’) was 83.7% for gadobutrol and 87.3% for gadopentate dimeglumine. The increase in accuracy from precontrast to combined precontrast and postcontrast MRI was 8.0% for gadobutrol and 6.9% for gadopentate dimeglumine. Sensitivity of the average reader was 85.2% for gadobutrol and 88.7% for gadopentate dimeglumine. Specificity of the average reader was 82.1% for gadobutrol and 86.1% for gadopentate dimeglumine. In conclusion, this study documents evidence for the noninferiority of a single i.v. bolus injection of 1.0 M gadobutrol compared with 0.5 M gadopentate dimeglumine in the diagnostic assessment of renal lesions with CE-MRI.

Surgery for ventricular tachycardia of left ventricular origin: risk factors for success and long-term outcome.

OBJECTIVES: To review 26 consecutive patients with sustained monomorphic ventricular tachycardia (VT) of left ventricular origin, who underwent direct VT surgery. METHODS: Economic factors precluded the use of an implantable cardioverter defibrillator (ICD) in the majority of these patients, and the indication for surgery in 81% of patients was for failed medical drug therapy and 27% of patients had frequent or incessant life-threatening VT. The principles of direct VT surgery included intraoperative mapping, extended endocardial resection, cryoablation, left ventricular aneurysm repair by left ventricular remodelling and endoaneurysmorrhaphy, as well as coronary artery bypass grafting. RESULTS: Two patients with non-ischaemic VT were significantly younger (37.7 +/- 19.4 years, P = 0.03), had lower preoperative New York Heart Association class (P = 0.03), and had better left ventricular ejection fractions of 59.5 +/- 2.1% (P = 0.001) than the 24 ischaemic patients. No operative mortality or recurrence of VT occurred in this group. Ischaemic VT patients had an operative mortality of 8.3%; risk factors were concomitant valve surgery (P = 0.02), and perioperative intra-aortic balloon pump (P = 0.02). Surgery improved the left ventricular ejection fraction from 28.4 +/- 9.8% to 43.2 +/- 8.2% (P = 0.0001). Freedom from recurrence or inducibility of VT in operative survivors was 78.8 +/- 9.6% at 10 years; risk factors were arrhythmic focus remote to the left ventricular aneurysm (P = 0.015), and simple cryoablation or endocardial resection alone and not in combination (P = 0.003). Survival was 54.1 +/- 11.6% and 43.3 +/- 13.4% at 5 and 10 years, respectively, and there were no arrhythmic or sudden cardiac deaths. Patients with immediately life-threatening VT unsuitable for ICD implantation requiring urgent or emergent VT surgery had a 10-year survival of 22.2 +/- 13.9% compared to the more elective surgical group with a rate of 73.3 +/- 13.9% (P = 0.08). CONCLUSIONS: Direct VT surgery should remain an objective for symptomatic drug refractory VT of left ventricular origin.     

Long-term Outcomes After Bladder-preserving Tri-modality Therapy for Patients with Muscle-invasive Bladder Cancer: An Updated Analysis of the Massachusetts General Hospital Experience

Background

Tri-modality therapy (TMT) is a recognized treatment strategy for selected patients with muscle-invasive bladder cancer (MIBC).

Online adaptive algorithm for optimal control of structures subjected to travelling loads

The problem of adaptive optimal semiactive control of a structure subjected to a moving load is studied. The control is realised by a change of damping of the structure's supports. The results presented in the previous works of the authors demonstrate that switched optimal controls can be very efficient at reducing the vibration levels of the structure. On the other hand, these controls exhibit a high sensitivity to changes of the speed of the travelling load. The aim of this paper is to develop an algorithm that enables real‐time adaptation of the optimal controls according to both the measured speed of the travelling load and the estimated state of the structure. The control objective is to provide smooth passage for the vehicles and reduce the material stresses on the carrying structures. The designed adaptive algorithm uses reference optimal controls computed for constant speeds and a set of functions describing the sensitivity of the system dynamics to the measured parameters. The convergence of the algorithm, as well as aspects of its implementation, is studied. The performance of the proposed method is validated by means of numerical simulations conducted for different travelling speed scenarios. In the assumed objective functional, the proposed adaptive controller can outperform the reference optimal solutions by over 50%. The practicality of the proposed method should attract the attention of practising engineers.     

Longitudinal assessment of renal size and function in extremely low birth weight children at 7 and 11 years of age

Background

There are a lack of studies describing a longitudinal association between preterm delivery and renal complications later in life. We assessed renal size and function in preterm infants born with extremely low birth weight (ELBW) during 4 years of follow-up, comparing these parameters to age-matched children born full term (term controls).

Methods

The results of selected renal laboratory tests [levels of cystatin C, creatinine, blood urea nitrogen (BUN)] and of renal ultrasound evaluations were compared between the ELBW group and the term control group at age 7 and 11 years.

Results

The study population consisted of 64 children born with ELBW (ELBW children) who had been recruited at birth and 36 children born at term (term children) who took part in both follow-up assessments. Renal ultrasound examination revealed a significantly smaller renal volume in the 7- and 11-year-old ELBW children compared to the term controls [right kidney volume: 50.8 vs. 61.2 ml/m², respectively, at 7 years (p <0.01) and 51.4 vs. 58.2 ml/m², respectively, at 11 years (p <0.01); left kidney volume: 51.4 vs. 60.3 ml/m², respectively, at 7 years (p <0.01) and 55.2 vs. 60.7 ml/m², respectively, at 11 years (p?=?0.02)]. Renal function in ELBW children was also affected. Serum cystatin C levels were significantly higher in ELBW children than in the controls at 7 years of age, and this difference remained statistically significant at 11 years of age [0.63 vs. 0.59 mg/l, respectively, at 7 years (p?=?0.02) and 0.72 vs. 0.61 mg/l, respectively, at 11 years (p?=?0.01)]. Six ELBW children also had elevated cystatin C levels (0.97–1.11 mg/l) at 11 years of age. Cystatin C levels were within normal range in the ELBW children at age 7 years and in term children in both follow-up studies. BUN levels were higher in ELBW children at the age of 11 years (4.49 vs. 4.15 mmol/l; p?=?0.028).

Conclusion

Continued follow-up of these patients will reveal whether the observed worsening in renal function will persist into adulthood.

     

Preassembled stentless valved-conduit for the replacement of the ascending aorta and aortic root

Here we report the early clinical results of a new preassembled stentless valved-conduit incorporating artificial sinuses of Valsalva (BioValsalva). This new composite conduit incorporates a stentless porcine aortic valve (Elan, Vascutek Terumo, UK) suspended within a triple-layered vascular conduit (Triplex, Vascutek Terumo, UK) constructed with sinuses of Valsalva. Between December 2006 and January 2008, 17 patients with the mean age of 65 years underwent aortic valve, root and ascending aorta replacement with the BioValsalva valved-conduit. There was no perioperative mortality. There were no myocardial infarctions, cardiac failure or cerebrovascular events. Mean cardiopulmonary bypass time was 156+/-56 min and ischemic time was 112+/-33 min. Eight patients required deep hypothermic circulatory arrest for additional distal ascending aorta replacement. Mean mediastinal drainage was 499+/-262 ml. Postoperative transthoracic echocardiography and CT-scans of the aorta in all patients before discharge demonstrated well-functioning prosthetic aortic valves with small residual mean gradients, no regurgitation, and the presence of sinuses of Valsalva. In conclusion, the novel prefabricated, composite stentless valved-conduit BioValsalva possesses excellent hemodynamic performance and can be implanted with low morbidity. In addition, the conduit material has good hemostatic properties which reduced bleeding, and is easy to implant with a variety of surgical techniques.     

Cause of Death in Multiorgan Donors and Its Relation to the Function of Transplanted Kidneys

Background

Brain death is an important variable contributing to donor-specific kidney damage. Poor kidney performance posttransplantation may be related to the cause of death of the donor.

Objective

To assess the influence of cause of death in multiorgan donors on the function of transplanted kidneys.

Material and Methods

Standard criteria for the brain stem death protocol were applied in 146 potential heart donors included in the study. Conventional supportive management consisted of mechanical ventilation to achieve normocapnia, rewarming, and fluid and electrolyte replacement. Dopamine infusion not exceeding 10 μg/kg/min and desaminovasopressin were titrated to predetermined mean arterial pressure (MAP). In renal allograft recipients (n = 232), kidney function was monitored using serial serum creatinine concentrations on days 1, 2, 3, 7, 14, 30, and 90 posttransplantation. The relation between donor cause of death (injury, bleeding, or other cause) and recipient serum creatinine concentration was analyzed in the postoperative period.

Results

Significantly greater serum creatinine concentrations were observed up to 14 days posttransplantation in recipients of a kidney from a donor who died of any cause other than injury. Recipients of a kidney from a donor who died of bleeding exhibited significantly greater serum creatinine concentrations at 30 days posttransplantation.

Conclusions

A cause of death other than injury or bleeding in a multiorgan donor is predictive of worse kidney graft function in the first 14 days posttransplantation. Intracranial bleeding in a multiorgan donor is predictive of worse kidney graft function in the early period posttransplantation.     

Arterial Hypertension due to Perirenal and Subcapsular Hematoma Induced by Renal Percutaneous Biopsy

In this study we report three patients, in whom arterial hypertension was induced by compression of the kidney parenchyma due to perirenal or subcapsular hematoma following percutaneous blind renal biopsy with use of Vim-Silverman type needle.     

HSP70-hom gene polymorphism in allogeneic hematopoietic stem-cell transplant recipients correlates with the development of acute graft-versus-host disease

BACKGROUND: A number of genetic polymorphisms have been shown to be associated with the outcome after allogeneic hematopoietic stem-cell transplantation (HSCT). In the present study, HSP70-hom polymorphism (+2763 G/A) was analyzed in the patients and donors of allogeneic HSCT in relation to transplantation outcome, susceptibility for generation of severe toxic lesions, and acute (a) graft-versus-host disease (GVHD). METHODS: One hundred thirty-three recipients of allogeneic hematopoietic stem cells and 64 haploidentical and matched unrelated donors were investigated. All these individuals were typed for dimorphism within the HSP70-hom gene (+2763 G/A) with the use of amplification refractory mutation system technique. RESULTS.: Patients with the HSP-AA homozygous genotype presented more frequently with grade II to IV toxic lesions (12 of 14 vs. 61 of 105, P = 0.039) and aGVHD (12 of 16 vs. 56 of 114, P = 0.045). Conversely, DRB1*11 was associated with a lower risk of aGVHD manifestation (10 of 31 vs. 58 of 99, P = 0.009). These contrary associations of HSP-AA and DRB1*11 with the risk of aGVHD were confirmed using logistic regression modeling in multivariable analysis (HSP-AA, odds ratio [OR] = 3.833, P = 0.004; DRB1*11, OR = 0.224, P = 0.048). None of donor HSP genotypes or patient-donor incompatibility within HSP alleles was associated with susceptibility to toxic complications or aGVHD. CONCLUSIONS: Polymorphism of the HSP70-hom gene is associated with the development of posttransplant complications. Recipient HSP-AA homozygous genotype is a risk factor for aGVHD.     

Effects of ranolazine on recurrent cardiovascular events in patients with non-ST-elevation acute coronary syndromes: the MERLIN-TIMI 36 randomized trial

Context  Ranolazine is a novel antianginal agent that reduces ischemia in patients with chronic angina but has not been studied in patients with acute coronary syndromes (ACS). Objective  To determine the efficacy and safety of ranolazine during long-term treatment of patients with non–ST-elevation ACS. Design, Setting, and Patients  A randomized, double-blind, placebo-controlled, multinational clinical trial of 6560 patients within 48 hours of ischemic symptoms who were treated with ranolazine (initiated intravenously and followed by oral ranolazine extended-release 1000 mg twice daily, n = 3279) or matching placebo (n = 3281), and followed up for a median of 348 days in the Metabolic Efficiency With Ranolazine for Less Ischemia in Non–ST-Elevation Acute Coronary Syndromes (MERLIN)-TIMI 36 trial between October 8, 2004, and February 14, 2007. Main Outcome Measures  The primary efficacy end point was a composite of cardiovascular death, myocardial infarction (MI), or recurrent ischemia through the end of study. The major safety end points were death from any cause and symptomatic documented arrhythmia. Results  The primary end point occurred in 696 patients (21.8%) in the ranolazine group and 753 patients (23.5%) in the placebo group (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.83-1.02; P = .11). The major secondary end point (cardiovascular death, MI, or severe recurrent ischemia) occurred in 602 patients (18.7%) in the ranolazine group and 625 (19.2%) in the placebo group (HR, 0.96; 95% CI, 0.86-1.08; P = .50). Cardiovascular death or MI occurred in 338 patients (10.4%) allocated to ranolazine and 343 patients (10.5%) allocated to placebo (HR, 0.99; 95% CI, 0.85-1.15; P = .87). Recurrent ischemia was reduced in the ranolazine group (430 [13.9%]) compared with the placebo group (494 [16.1%]; HR, 0.87; 95% CI, 0.76-0.99; P = .03). QTc prolongation requiring a reduction in the dose of intravenous drug occurred in 31 patients (0.9%) receiving ranolazine compared with 10 patients (0.3%) receiving placebo. Symptomatic documented arrhythmias did not differ between the ranolazine (99 [3.0%]) and placebo (102 [3.1%]) groups (P = .84). No difference in total mortality was observed with ranolazine compared with placebo (172 vs 175; HR, 0.99; 95% CI, 0.80-1.22; P = .91). Conclusions  The addition of ranolazine to standard treatment for ACS was not effective in reducing major cardiovascular events. Ranolazine did not adversely affect the risk of all-cause death or symptomatic documented arrhythmia. Our findings provide support for the safety and efficacy of ranolazine as antianginal therapy. Trial Registration  clinicaltrials.gov Identifier: NCT00099788