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Headache and migraine in children with sickle cell disease are associated with lower hemoglobin and higher pain event rates but not silent cerebral infarction.
Dowling MM, Noetzel MJ, Rodeghier MJ, Quinn CT, Hirtz DG, Ichord RN, Kwiatkowski JL, Roach ES, Kirkham FJ, Casella JF, DeBaun MR
(2014) J Pediatr 164: 1175-1180.e1
MeSH Terms: Adolescent, Anemia, Sickle Cell, Biomarkers, Blood Transfusion, Cerebral Infarction, Child, Child, Preschool, Cross-Sectional Studies, Female, Headache, Hemoglobins, Humans, Logistic Models, Magnetic Resonance Imaging, Male, Migraine Disorders, Multivariate Analysis, Pain, Recurrence, Risk Factors, Severity of Illness Index
Show Abstract · Added February 19, 2014
OBJECTIVE - To identify risk factors for headache and migraine in children with sickle cell disease and test the hypothesis that either or both are independently associated with silent cerebral infarcts.
STUDY DESIGN - In this cross-sectional study, we evaluated the health history, laboratory values, and brain magnetic resonance imaging findings of participants with sickle cell disease (hemoglobinSS or hemoglobinSβ°-thalassemia) with no history of overt stroke or seizures. Participants characterized headache severity and quality. Migraine was defined by International Headache Society criteria modified for increased sensitivity in children. Neuroradiology and neurology committees adjudicated the presence of silent cerebral infarction by review of magnetic resonance imaging and standardized examination by pediatric neurologists.
RESULTS - The cohort included 872 children (51.1% males), ranging in age from 5 to 15 years (mean age, 9.1 years). Of these children, 317 (36.4%) reported recurrent headaches, and 132 (15.1%) reported migraines. In multivariable logistic regression analyses, both were associated with lower steady-state hemoglobin (P = .01 for headaches; P < .01 for migraines) and higher pain rate (P < .01 for headaches; P < .01 for migraines), defined as the number of admissions requiring opioids in the previous 3 years. The presence of silent cerebral infarction was not associated with recurrent headaches or migraines. Only 1.9% (6 of 317) of children with recurrent headaches received medication for headache prophylaxis.
CONCLUSION - Recurrent headaches and migraines are common and undertreated in children with sickle cell disease. Low hemoglobin levels and high pain rates are associated with recurrent headaches and migraines; whereas, silent cerebral infarction is not.
Copyright © 2014 Elsevier Inc. All rights reserved.
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21 MeSH Terms
The case for and against initiating either hydroxyurea therapy, blood transfusion therapy or hematopoietic stem cell transplant in asymptomatic children with sickle cell disease.
Kassim AA, DeBaun MR
(2014) Expert Opin Pharmacother 15: 325-36
MeSH Terms: Anemia, Sickle Cell, Antisickling Agents, Blood Transfusion, Chest Pain, Child, Hematopoietic Stem Cell Transplantation, Humans, Hydroxyurea, Models, Statistical, Pain, Stroke
Show Abstract · Added February 19, 2014
INTRODUCTION - The perception of an asymptomatic sickle cell disease (SCD) state is a misnomer. Children without overt symptoms, likely have subclinical disease beginning in infancy with progression into adulthood. Predictive models of SCD severity are unable to predict a subgroup of asymptomatic children likely to develop severe SCD. The introduction of penicillin prophylaxis, conjugated pneumococcal and Haemophilus influenzae type B vaccines have dramatically decreased the rate of life-threatening infections, while use of hydroxyurea in children has decreased pain and acute chest syndrome events. Use of transcranial Doppler coupled with regular blood transfusion therapy has decreased the rate of overt strokes and premature death associated with strokes. Currently, therapy for asymptomatic children includes hydroxyurea, regular blood transfusion or allogeneic hematopoietic stem cell transplant (allo-HSCT).
AREAS COVERED - The pros and cons of initiating hydroxyurea, regular blood transfusion or allo-HSCT in asymptomatic children with SCD.
EXPERT OPINION - Emerging evidence from observational studies indicates that hydroxyurea prolongs survival in children and adults with sickle cell anemia. Regular blood transfusions reduce incidence of strokes, acute chest and pain episodes, but is associated with the burden of monthly visits and excessive iron stores. Although curative, the perceived risk:benefit ratio associated with allo-HSCT limits its use in asymptomatic children.
1 Communities
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11 MeSH Terms
Blood loss associated with radical cystectomy: a prospective, randomized study comparing Impact LigaSure vs. stapling device.
Thompson IM, Kappa SF, Morgan TM, Barocas DA, Bischoff CJ, Keegan KA, Stratton KL, Clark PE, Resnick MJ, Smith JA, Cookson MS, Chang SS
(2014) Urol Oncol 32: 45.e11-5
MeSH Terms: Aged, Blood Loss, Surgical, Blood Transfusion, Carcinoma, Transitional Cell, Cystectomy, Female, Humans, Ligation, Male, Middle Aged, Outcome Assessment, Health Care, Prospective Studies, Sutures, Urinary Bladder Neoplasms
Show Abstract · Added March 7, 2014
OBJECTIVES - Radical cystectomy (RC) is associated with significant blood loss and transfusion requirement. We performed a prospective, randomized trial to compare blood loss, operative time, and cost using 2 different and commonly employed approaches to tissue ligation and division during RC: mechanical (stapler device) and electrosurgical (heat-sealing device).
METHODS AND MATERIALS - Eighty patients undergoing RC for urothelial bladder carcinoma were randomized to use of either an Endo GIA Stapler or Impact LigaSure device for tissue ligation and division. Primary outcomes were blood loss, operative time, and device costs. Data were analyzed with Wilcoxon rank sum test and Welch 2-sample t test.
RESULTS - There were no significant demographic or preoperative differences between the cohorts. Mean estimated blood loss was similar between the electrosurgical (687 ml) and stapler (708 ml) arms (P = 0.850). There were no significant differences between cohorts when comparing operative times or transfusion requirement. There was a significant increase in the mean number of adjunctive suture ligatures used in the stapling device arm (3.0 vs. 1.5, P = 0.047). Total device costs were significantly lower with the LigaSure compared with the GIA Stapler ($625.00 vs. $1490.10, P<0.001). There were no complications attributable to either device.
CONCLUSIONS - This prospective, randomized study demonstrates no significant difference in blood loss, transfusion requirement, or safety between mechanical vs. electrosurgical control of the vascular pedicles. The LigaSure device, however, is significantly less costly than the GIA Stapler and required fewer additional measures for hemostasis.
Copyright © 2014 Elsevier Inc. All rights reserved.
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14 MeSH Terms
Contribution of endogenous bradykinin to fibrinolysis, inflammation, and blood product transfusion following cardiac surgery: a randomized clinical trial.
Balaguer JM, Yu C, Byrne JG, Ball SK, Petracek MR, Brown NJ, Pretorius M
(2013) Clin Pharmacol Ther 93: 326-34
MeSH Terms: Aminocaproic Acid, Antifibrinolytic Agents, Blood Transfusion, Bradykinin, Bradykinin Receptor Antagonists, Cardiopulmonary Bypass, Female, Fibrin Fibrinogen Degradation Products, Fibrinolysis, Humans, Inflammation, Male, Middle Aged, Postoperative Complications, Postoperative Hemorrhage
Show Abstract · Added December 10, 2013
Bradykinin increases during cardiopulmonary bypass (CPB) and stimulates the release of nitric oxide, inflammatory cytokines, and tissue-type plasminogen activator (t-PA), acting through its B2 receptor. This study tested the hypothesis that endogenous bradykinin contributes to the fibrinolytic and inflammatory response to CPB and that bradykinin B2 receptor antagonism reduces fibrinolysis, inflammation, and subsequent transfusion requirements. Patients (N = 115) were prospectively randomized to placebo, ε-aminocaproic acid (EACA), or HOE 140, a bradykinin B2 receptor antagonist. Bradykinin B2 receptor antagonism decreased intraoperative fibrinolytic capacity as much as EACA, but only EACA decreased D-dimer formation and tended to decrease postoperative bleeding. Although EACA and HOE 140 decreased fibrinolysis and EACA attenuated blood loss, these treatments did not reduce the proportion of patients transfused. These data suggest that endogenous bradykinin contributes to t-PA generation in patients undergoing CPB, but that additional effects on plasmin generation contribute to decreased D-dimer concentrations during EACA treatment.
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15 MeSH Terms
Comparison of Impella and intra-aortic balloon pump in high-risk percutaneous coronary intervention: vascular complications and incidence of bleeding.
Boudoulas KD, Pederzolli A, Saini U, Gumina RJ, Mazzaferri EL, Davis M, Bush CA, Capers Q, Magorien R, Pompili VJ
(2012) Acute Card Care 14: 120-4
MeSH Terms: Acute Coronary Syndrome, Aged, Blood Transfusion, Coronary Stenosis, Female, Gastrointestinal Hemorrhage, Heart-Assist Devices, Hematocrit, Hemodynamics, Hemorrhage, Hospital Mortality, Humans, Intra-Aortic Balloon Pumping, Male, Middle Aged, Retrospective Studies
Show Abstract · Added February 21, 2015
OBJECTIVE - Compare vascular complications and incidence of bleeding of Impella 2.5 and intra-aortic balloon pump (IABP) in high-risk percutaneous coronary interventions (PCI).
BACKGROUND - Large arterial sheath size for device insertion is associated with vascular and/or bleeding complications; gastrointestinal bleeding may also occur with anti-coagulation use.
METHODS - Patients with an acute coronary syndrome receiving Impella 2.5 or IABP during high-risk PCI were studied (13 Impella; 62 IABP). Vascular complications and incidence of bleeding were compared.
RESULTS - Post-procedure hematocrit was similar between groups. Blood transfusion occurred in 38.4% and 32.2% of patients in the Impella and IABP groups, respectively (P = NS); 65.3%, 30.7% and 3.8% of bleeding were due to vascular access site/procedure related, gastrointestinal and genitourinary, respectively. There was no statistical significant difference in vascular complications between the Impella and IABP groups (15.3% and 6.4% of patients, respectively); mesenteric ischemia (n = 1) and aortic rupture (n = 1) were only in the IABP group. In-hospital and one-year mortality were not statistically significant between groups.
CONCLUSION - Impella can be used as safely as IABP during high-risk PCI with similar vascular and bleeding complications. Importantly, approximately one third of bleeding was from the gastrointestinal system warranting careful prophylactic measures and monitoring.
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16 MeSH Terms
Magnetic resonance angiography-defined intracranial vasculopathy is associated with silent cerebral infarcts and glucose-6-phosphate dehydrogenase mutation in children with sickle cell anaemia.
Thangarajh M, Yang G, Fuchs D, Ponisio MR, McKinstry RC, Jaju A, Noetzel MJ, Casella JF, Barron-Casella E, Hooper WC, Boulet SL, Bean CJ, Pyle ME, Payne AB, Driggers J, Trau HA, Vendt BA, Rodeghier M, DeBaun MR
(2012) Br J Haematol 159: 352-9
MeSH Terms: Adolescent, Anemia, Sickle Cell, Blood Transfusion, Cerebral Infarction, Child, Child, Preschool, Female, Glucosephosphate Dehydrogenase, Humans, Magnetic Resonance Angiography, Male, Mutation, Sex Factors, alpha-Globins
Show Abstract · Added November 27, 2013
Silent cerebral infarct (SCI) is the most commonly recognized cause of neurological injury in sickle cell anaemia (SCA). We tested the hypothesis that magnetic resonance angiography (MRA)-defined vasculopathy is associated with SCI. Furthermore, we examined genetic variations in glucose-6-phosphate dehydrogenase (G6PD) and HBA (α-globin) genes to determine their association with intracranial vasculopathy in children with SCA. Magnetic resonance imaging (MRI) of the brain and MRA of the cerebral vasculature were available in 516 paediatric patients with SCA, enrolled in the Silent Infarct Transfusion (SIT) Trial. All patients were screened for G6PD mutations and HBA deletions. SCI were present in 41·5% (214 of 516) of SIT Trial children. The frequency of intracranial vasculopathy with and without SCI was 15·9% and 6·3%, respectively (P < 0·001). Using a multivariable logistic regression model, only the presence of a SCI was associated with increased odds of vasculopathy (P = 0·0007, odds ratio (OR) 2·84; 95% Confidence Interval (CI) = 1·55-5·21). Among male children with SCA, G6PD status was associated with vasculopathy (P = 0·04, OR 2·78; 95% CI = 1·04-7·42), while no significant association was noted for HBA deletions. Intracranial vasculopathy was observed in a minority of children with SCA, and when present, was associated with G6PD status in males and SCI.
© 2012 Blackwell Publishing Ltd.
1 Communities
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14 MeSH Terms
Intraoperative use of low-dose recombinant activated factor VII during thoracic aortic operations.
Andersen ND, Bhattacharya SD, Williams JB, Fosbol EL, Lockhart EL, Patel MB, Gaca JG, Welsby IJ, Hughes GC
(2012) Ann Thorac Surg 93: 1921-8; discussion 1928-9
MeSH Terms: Aged, Aorta, Thoracic, Blood Coagulation Tests, Blood Transfusion, Blood Vessel Prosthesis Implantation, Cardiopulmonary Bypass, Cohort Studies, Critical Pathways, Dose-Response Relationship, Drug, Factor VIIa, Female, Heart Arrest, Induced, Hemostasis, Surgical, Hospital Costs, Humans, Intraoperative Period, Male, Matched-Pair Analysis, Middle Aged, Postoperative Hemorrhage, Propensity Score, Recombinant Proteins
Show Abstract · Added June 14, 2016
BACKGROUND - Numerous studies have supported the effectiveness of recombinant activated factor VII (rFVIIa) for the control of bleeding after cardiac procedures; however safety concerns persist. Here we report the novel use of intraoperative low-dose rFVIIa in thoracic aortic operations, a strategy intended to improve safety by minimizing rFVIIa exposure.
METHODS - Between July 2005 and December 2010, 425 consecutive patients at a single referral center underwent thoracic aortic operations with cardiopulmonary bypass (CPB); 77 of these patients received intraoperative low-dose rFVIIa (≤60 μg/kg) for severe coagulopathy after CPB. Propensity matching produced a cohort of 88 patients (44 received intraoperative low-dose rFVIIa and 44 controls) for comparison.
RESULTS - Matched patients receiving intraoperative low-dose rFVIIa got an initial median dose of 32 μg/kg (interquartile range [IQR], 16-43 μg/kg) rFVIIa given 51 minutes (42-67 minutes) after separation from CPB. Patients receiving intraoperative low-dose rFVIIa demonstrated improved postoperative coagulation measurements (partial thromboplastin time 28.6 versus 31.5 seconds; p=0.05; international normalized ratio, 0.8 versus 1.2; p<0.0001) and received 50% fewer postoperative blood product transfusions (2.5 versus 5.0 units; p=0.05) compared with control patients. No patient receiving intraoperative low-dose rFVIIa required postoperative rFVIIa administration or reexploration for bleeding. Rates of stroke, thromboembolism, myocardial infarction, and other adverse events were equivalent between groups.
CONCLUSIONS - Intraoperative low-dose rFVIIa led to improved postoperative hemostasis with no apparent increase in adverse events. Intraoperative rFVIIa administration in appropriately selected patients may correct coagulopathy early in the course of refractory blood loss and lead to improved safety through the use of smaller rFVIIa doses. Appropriately powered randomized studies are necessary to confirm the safety and efficacy of this approach.
Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
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22 MeSH Terms
Comparative effects of angiotensin receptor blockade and ACE inhibition on the fibrinolytic and inflammatory responses to cardiopulmonary bypass.
Billings FT, Balaguer JM, C Y, Wright P, Petracek MR, Byrne JG, Brown NJ, Pretorius M
(2012) Clin Pharmacol Ther 91: 1065-73
MeSH Terms: Aged, Angiotensin II Type 1 Receptor Blockers, Angiotensin-Converting Enzyme Inhibitors, Benzimidazoles, Blood Transfusion, Bradykinin, Cardiopulmonary Bypass, Endpoint Determination, Female, Fibrinolysis, Hematocrit, Hospital Mortality, Humans, Inflammation, Interleukins, Length of Stay, Male, Middle Aged, Monitoring, Intraoperative, Perioperative Care, Postoperative Complications, Ramipril, Tetrazoles, Treatment Outcome
Show Abstract · Added December 10, 2013
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.
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24 MeSH Terms
Prospects for primary stroke prevention in children with sickle cell anaemia.
Jordan LC, Casella JF, DeBaun MR
(2012) Br J Haematol 157: 14-25
MeSH Terms: Adolescent, Anemia, Sickle Cell, Antisickling Agents, Bacterial Infections, Blood Transfusion, Brain Ischemia, Child, Child, Preschool, Female, Hematopoietic Stem Cell Transplantation, Humans, Hydroxyurea, Immunization, Male, Stroke, Transplantation, Homologous
Show Abstract · Added November 27, 2013
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.
1 Communities
1 Members
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16 MeSH Terms
What is the evidence for using hydroxyurea for secondary stroke prevention?
Lebensburger JD, DeBaun MR, Thompson AA
(2011) Hematology Am Soc Hematol Educ Program 2011: 440-2
MeSH Terms: Blood Transfusion, Child, Humans, Hydroxyurea, Male, Secondary Prevention, Stroke
Show Abstract · Added November 27, 2013
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.
1 Communities
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7 MeSH Terms