Renal Responses to Long-Term Carotid Baroreflex Activation Therapy in Patients With Drug-Resistant Hypertension.

Renal Responses to Long-Term Carotid Baroreflex Activation Therapy in Patients With Drug-Resistant Hypertension.

Hypertension. 2013 Apr 15;
Alnima T, de Leeuw PW, Tan FE, Kroon AA,

Carotid baroreflex activation has been demonstrated to provide enduring reductions in arterial blood pressure. The aim of this study was to investigate the effect of long-term therapy on renal function. A total of 322 patients were enrolled in the Rheos Pivotal Trial. Group 1 consisted of 236 patients who started baroreflex activation therapy 1 month after device implantation, whereas in the 86 patients from group 2 the device was activated 6 months later. Serum creatinine and urine albumin/creatinine ratio were collected at screening (before device activation), and at months 6 and 12. Multilevel statistical analyses were adjusted for various covariables. Serum creatinine increased from 78 to 84 ?mol/L, and glomerular filtration rate decreased from 92 to 87 mL/min per 1.73 m(2) in group 1 at month 6 (P<0.05). These values did not change any further after 12 months of therapy. Patients with highest glomerular filtration rate showed the greatest decrease in glomerular filtration. Group 2 showed the same trends as group 1 even before device activation at month 6. Systolic blood pressure reduction seemed to be significantly related to the change in glomerular filtration rate in both groups. Albumin/creatinine ratio did not change in both groups during follow-up. In conclusion, baroreflex activation therapy in hypertensive patients is associated with an initial mild decrease in glomerular filtration rate, which may be considered as a normal hemodynamic response to the drop in blood pressure. Long-term treatment does not result in further decrease in renal function, indicating baroreflex activation as a safe and effective therapy. HubMed – drug

 

Reduced Neuroanatomic Volumes in Long-Term Survivors of Childhood Acute Lymphoblastic Leukemia.

J Clin Oncol. 2013 Apr 15;
Zeller B, Tamnes CK, Kanellopoulos A, Amlien IK, Andersson S, Due-T√łnnessen P, Fjell AM, Walhovd KB, Westlye LT, Ruud E

PURPOSETo compare regional brain volumes in adult long-term survivors of childhood acute lymphoblastic leukemia (ALL) and healthy controls. PATIENTS AND METHODSWe investigated 130 survivors of childhood ALL diagnosed between 1970 and 2002 with magnetic resonance imaging (MRI) and neuropsychological testing at a median of 22.5 years after diagnosis. Morphometric analyses including whole-brain segmentation were performed using a validated automated procedure; 130 healthy adults served as controls.ResultsCompared with healthy controls, ALL survivors showed significantly smaller volumes of cortical gray matter, cerebral white matter, amygdala, caudate, hippocampus, thalamus, and estimated intracranial volume. Effect sizes ranged from small to medium. The strongest effect was found for the caudate, which on average was 5.2% smaller in ALL survivors. Caudate volumes were also smaller when controlling for intracranial volume, suggesting a specific effect. Neither age at diagnosis nor treatment variables such as radiation therapy or drug dose had a major impact on neuroanatomic volumes. Neuropsychological assessment revealed reduced processing speed, executive function, and verbal learning/memory in survivors compared with controls but no difference in estimated general intellectual ability. In ALL survivors, but not in controls, neuropsychological test results correlated with volumes of cortical gray matter, caudate, and thalamus as well as intracranial volume. CONCLUSIONStructural MRI of long-term survivors of childhood ALL demonstrated smaller volumes of multiple brain structures compared with healthy controls. Because of possible selection biases, these results must be interpreted with caution. Future studies are required to clarify the significance of these findings and the neurobiologic mechanisms involved. HubMed – drug

 

Future of Clinical Genomics in Pediatric Oncology.

J Clin Oncol. 2013 Apr 15;
Janeway KA, Place AE, Kieran MW, Harris MH

The somatic genomic alterations in pediatric cancers to some extent overlap with those seen in adult cancers, but the exact distribution throughout the genome and the types and frequency of alterations differ. The ultimate goal of genomic research in children, as with adults, is translation to the clinic to achieve more accurate diagnosis, more precise risk stratification, and more effective, less toxic therapy. The genomic features of pediatric malignancies and pediatric-specific issues in clinical investigation may make translating genomic discoveries to the clinic more difficult. However, through large-scale molecular profiling of pediatric tumors, continued coordinated efforts to evaluate novel therapies in the pediatric population, thoughtful phase II and III trial design, and continued drug development, genomically based therapies will become more common in the pediatric oncology clinic in the future. HubMed – drug