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The effects of angiotensin-converting enzyme (ACE) inhibition and angiotensin II type 1 receptor blockade (ARB) on fibrinolysis and inflammation after cardiopulmonary bypass (CPB) are uncertain. This study tested the hypothesis that ACE inhibition enhances fibrinolysis and inflammation to a greater extent than ARB in patients undergoing CPB. One week to 5 days before surgery, patients were randomized to ramipril 5 mg/day, candesartan 16 mg/day, or placebo. ACE inhibition increased intraoperative bradykinin and tissue-type plasminogen activator (t-PA ) concentrations as compared to AR B. Both ACE inhibition and AR B decreased the need for plasma transfusion relative to placebo, but only ACE inhibition decreased the duration of hospital stay. Neither ACE inhibition nor AR B significantly affected concentrations of plasminogen activator inhibitor-1 (PAI -1), interleukin (IL )-6, IL -8, or IL -10. ACE inhibition enhanced intraoperative fibrinolysis without increasing the likelihood of red-cell transfusion. By contrast, neither ACE inhibition nor ARB affected the inflammatory response. ACE inhibitors and ARBs may be safely continued until the day of surgery.
This review will focus on the strengths and limitations associated with the current standard of care for primary prevention of ischaemic strokes in children with sickle cell anaemia (SCA) - transcranial Doppler ultrasound (TCD) screening followed by regular blood transfusion therapy when TCD measurement is above a threshold defined by a randomized clinical trial (RCT). The theoretical basis for potential alternative strategies for primary prevention of neurological injury in SCA is also discussed. These strategies will include, but will not be limited to: immunizations to prevent bacterial infections, particularly in low income countries; management of elevated blood pressure; and targeted strategies to increase baseline haemoglobin levels with therapies such as hyroxycarbamide or potentially definitive haematopoietic stem cell transplant.
© 2012 Blackwell Publishing Ltd.
A 10-year-old male patient with hemoglobin SS suffered a stroke at 7 years of age and was initially transfused at the time of presentation to lower the hemoglobin S concentration to < 30%. You are asked by the family if their child can be treated with oral hydroxyurea rather than monthly transfusions for the secondary prevention of strokes.
The most common form of neurologic injury in sickle cell anemia (SCA) is silent cerebral infarction (SCI). In the Silent Cerebral Infarct Multi-Center Clinical Trial, we sought to identify risk factors associated with SCI. In this cross-sectional study, we evaluated the clinical history and baseline laboratory values and performed magnetic resonance imaging of the brain in participants with SCA (HbSS or HbSβ° thalassemia) between the ages of 5 and 15 years with no history of overt stroke or seizures. Neuroradiology and neurology committees adjudicated the presence of SCI. SCIs were diagnosed in 30.8% (251 of 814) participants who completed all evaluations and had valid data on all prespecified demographic and clinical covariates. The mean age of the participants was 9.1 years, with 413 males (50.7%). In a multivariable logistic regression analysis, lower baseline hemoglobin concentration (P < .001), higher baseline systolic blood pressure (P = .018), and male sex (P = .030) were statistically significantly associated with an increased risk of an SCI. Hemoglobin concentration and systolic blood pressure are risk factors for SCI in children with SCA and may be therapeutic targets for decreasing the risk of SCI. This study is registered at www.clinicaltrials.gov as #NCT00072761.
BACKGROUND/AIMS - Percutaneous kidney biopsy (PKB) is the primary diagnostic tool for kidney disease. Outpatient 'day surgery' (ODS) following PKB in low-risk patients has previously been described as a safe alternative to inpatient observation (IO). This study aims to determine if ODS is less costly compared to IO while accounting for all institutional costs (IC) associated with post-PKB complications, including death.
METHODS - A cost minimization study was performed using decision analysis methodology which models relative costs in relation to outcome probabilities yielding an optimum decision. The potential outcomes included major complications (bleeding requiring blood transfusion or advanced intervention), minor complications (bleeding or pain requiring additional observation), and death. Probabilities were obtained from the published literature and a base case was selected. IC were obtained for all complications from institutional activity-based cost estimates. The base case assumed a complication rate of 10% with major bleeding occurring in 2.5% of patients (for both arms) and death in 0.1 and 0.15% of IO and ODS patients, respectively.
RESULTS - ODS costs USD 1,394 per biopsy compared to USD 1,800 for IO inclusive of all complications. IC for ODS remain less when overall complications <20%, major complications <5.5%, and IC per death
CONCLUSION - Outpatient management after PKB for low-risk patients costs less from the institutional perspective compared to IO, inclusive of complications and death. ODS should be considered for low-risk patients undergoing native kidney biopsy.
Copyright © 2011 S. Karger AG, Basel.
BACKGROUND - A doctor's diagnosis of asthma is associated with increased morbidity (pain and acute chest syndrome [ACS]) among children with sickle cell disease (SCD). An association between IgE levels and asthma and morbidity has not been investigated in children with SCD.
OBJECTIVE - We tested the hypothesis that elevated total and allergen-specific IgE levels are associated with asthma and SCD morbidity in children with SCD.
METHODS - A cross-sectional study of children with SCD who participated in the Silent Cerebral Infarct Trial was conducted. Logistic regression and negative binomial regression were used to investigate potential associations of total and allergen-specific IgE levels with asthma diagnosis and SCD morbidity, both confirmed by medical record review. Elevation of total IgE level was defined as age-adjusted and sex-adjusted IgE level exceeding the 90th percentile compared with a nonatopic reference population. IgE antibody positivity to Alternaria alternata (mold), Blattellagermanica (cockroach), and Dermatophagoides pteronyssinus (dust mite) was assessed by ImmunoCAP analysis.
RESULTS - Children with SCD (140 with asthma; 381 without asthma) were evaluated. Elevations in total IgE level (P = .04) and IgE antibody specific for Alternaria alternata (P = .0003), Blattella germanica (P = .008), and Dermatophagoides pteronyssinus (P = .01) were associated with asthma. ACS (P = .048) but not pain (P = .20) was associated with total IgE level, but neither was associated with specific IgE levels.
CONCLUSION - Significantly increased levels of total and allergen-specific IgE levels are associated with asthma in SCD. High IgE levels are a risk factor for ACS but not pain rates.
Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
Children with sickle cell disease (SCD) and strokes receive blood transfusion therapy for secondary stroke prevention; despite this, approximately 20% experience second overt strokes. Given this rate of second overt strokes and the clinical significance of silent cerebral infarcts, we tested the hypothesis that silent cerebral infarcts occur among children with SCD being transfused for secondary stroke prevention. A prospective cohort enrolled children with SCD and overt strokes at 7 academic centers. Magnetic resonance imaging and magnetic resonance angiography of the brain were scheduled approximately every 1 to 2 years; studies were reviewed by a panel of neuroradiologists. Eligibility criteria included regularly scheduled blood transfusion therapy. Forty children were included; mean pretransfusion hemoglobin S concentration was 29%. Progressive cerebral infarcts occurred in 45% (18 of 40 children) while receiving chronic blood transfusion therapy; 7 had second overt strokes and 11 had new silent cerebral infarcts. Worsening cerebral vasculopathy was associated with new cerebral infarction (overt or silent; relative risk = 12.7; 95% confidence interval, 2.65-60.5, P = .001). Children with SCD and overt strokes receiving regular blood transfusion therapy experience silent cerebral infarcts at a higher rate than previously recognized. Additional therapies are needed for secondary stroke prevention in children with SCD.
BACKGROUND - Silent cerebral infarct (SCI) is the most common cause of serious neurological disease in sickle cell anemia (SCA), affecting approximately 22% of children. The goal of this trial is to determine whether blood transfusion therapy will reduce further neurological morbidity in children with SCI, and if so, the magnitude of this benefit.
PROCEDURE - The Silent Cerebral Infarct Transfusion (SIT) Trial includes 29 clinical sites and 3 subsites, a Clinical Coordinating Center, and a Statistical and Data Coordinating Center, to test the following hypothesis: prophylactic blood transfusion therapy in children with SCI will result in at least an 86% reduction in the rate of subsequent overt strokes or new or progressive cerebral infarcts as defined by magnetic resonance imaging (MRI) of the brain. The intervention is blood transfusion versus observation. Two hundred and four participants (102 in each treatment assignment) will ensure 85% power to detect the effect necessary to recommend transfusion therapy (86% reduction), after accounting for 10% drop out and 19% crossover rates. MRI examination of the brain is done at screening, immediately before randomization and study exit. Each randomly assigned participant receives a cognitive test battery at study entry, 12-18 months later, and study exit and an annual neurological examination. Blood is obtained from all screened participants for a biologic repository containing serum and a renewable source of DNA.
CONCLUSION - The SIT Trial could lead to a change in standard care practices for children affected with SCA and SCI, with a consequent reduction in neurological morbidity.
OBJECTIVE - To determine whether robotic-assisted laparoscopic radical prostatectomy (RALP) is associated with a lower transfusion rate than radical retropubic prostatectomy (RRP).
PATIENTS AND METHODS - In this cohort study, we evaluated 1244 consecutive patients who underwent RALP (830) or RRP (414) between June 2003 and July 2006. Demographics, clinical characteristics, pathology, blood loss and transfusion data were collected prospectively. Groups were compared for baseline characteristics, blood loss, change in haematocrit and transfusion using univariate statistics, and an exploratory multivariate model was developed.
RESULTS - RALP was associated with lower blood loss (median 100 vs 450 mL, P < 0.001) and a smaller change in haematocrit (median 7% vs 10%, P < 0.001) than RRP. Although both groups had low transfusion rates, the RALP group required fewer transfusions than the RRP group (0.8% vs 3.4%, P= 0.002). On univariate analysis, surgical approach (RRP vs RALP), estimated blood loss ≥500 mL and change in haematocrit ≥10% were the only the significant predictors of transfusion. In the exploratory multivariate model RALP was the only significant predictor of reduced need for transfusion, with an odds ratio of 0.23 (95% confidence interval 0.09-0.58; P= 0.002).
CONCLUSIONS - This study shows that RALP is associated not only with less blood loss and a smaller decrease in haematocrit, but also a decreased need for transfusion.
© 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.
Advances in pediatric bone marrow transplantation (BMT) are slowed by the small number of patients with a given disease who undergo transplantation, a lack of sufficient infrastructure to run early-phase oncology protocols and studies of rare nonmalignant disorders, and challenges associated with funding multi-institutional trials. Leadership of the Pediatric Blood and Marrow Transplant Consortium (PBMTC), a large pediatric BMT clinical trials network representing 77 active and 45 affiliated centers worldwide, met in April 2009 to develop strategic plans to address these issues. Key barriers, including infrastructure development and funding, along with scientific initiatives in malignant and nonmalignant disorders, cellular therapeutics, graft-versus-host disease, and supportive care were discussed. The PBMTC's agenda for approaching these issues will result in infrastructure and trials specific to pediatrics that will run through the PBMTC or its partners, the Blood and Marrow Transplant Clinical Trials Network and the Children's Oncology Group.
Copyright (c) 2010 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.