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Interleukin-10 haplotypes are not associated with acute cerebral ischemia or high-risk transcranial Doppler in a newborn cohort of 395 children with sickle cell anemia.

ABSTRACT: BACKGROUND:The etiology of stroke, a severe complication of sickle cell anemia, involves inflammatory processes. However, the pathogenetic mechanisms are unknown. The aim of this study was to evaluate the influence of interleukin-10 polymorphisms and haplotypes on the risk of acute cerebral ischemia and high-risk transcranial Doppler in 395 children with sickle cell anemia from the state of Minas Gerais, Brazil. METHODS:Interleukin-10 haplotypes were determined by polymerase chain reaction-restriction fragment length polymorphism and sequencing. The outcomes studied were acute cerebral ischemia and high-risk transcranial Doppler. Clinical data were retrieved from the children's records. RESULTS:There was no statistically significant difference in the frequencies of polymorphisms and haplotypes between children with and without acute cerebral ischemia or children with or without high-risk transcranial Doppler. These data are consistent with a previous report that showed an absence of association between interleukin-10 plasma levels and high-risk transcranial Doppler velocity in children with sickle cell anemia. CONCLUSION:Interleukin-10 haplotypes were not associated with the risk of acute cerebral ischemia or high-risk transcranial Doppler velocity in children with sickle cell anemia from the state of Minas Gerais, Brazil.

SUBMITTER: Belisario AR

PROVIDER: S-EPMC5457462 | biostudies-literature | 2017 Apr - Jun

REPOSITORIES: biostudies-literature

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Interleukin-10 haplotypes are not associated with acute cerebral ischemia or high-risk transcranial Doppler in a newborn cohort of 395 children with sickle cell anemia.

Belisário André Rolim AR Sales Rahyssa Rodrigues RR Toledo Nayara Evelin NE Velloso-Rodrigues Cibele C Silva Célia Maria CM Viana Marcos Borato MB

Revista brasileira de hematologia e hemoterapia 20170221 2

<h4>Background</h4>The etiology of stroke, a severe complication of sickle cell anemia, involves inflammatory processes. However, the pathogenetic mechanisms are unknown. The aim of this study was to evaluate the influence of interleukin-10 polymorphisms and haplotypes on the risk of acute cerebral ischemia and high-risk transcranial Doppler in 395 children with sickle cell anemia from the state of Minas Gerais, Brazil.<h4>Methods</h4>Interleukin-10 haplotypes were determined by polymerase chain ...[more]

PMID: 28577646

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Project description:ImportanceIn children with sickle cell anemia (SCA), high transcranial Doppler (TCD) velocities are associated with stroke risk, which is reduced by chronic transfusion. Whether matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) can reduce velocities in patients with SCA is unknown.ObjectiveTo determine the association of MSD-HSCT with TCD velocities as a surrogate for the occurrence of ischemic stroke in children with SCA.Design, setting, and participantsNonrandomized controlled intervention study conducted at 9 French centers. Patients with SCA were enrolled between December 2010 and June 2013, with 3-year follow-up ending in January 2017. Children with SCA were eligible if younger than 15 years, required chronic transfusions for persistently elevated TCD velocities, and had at least 1 sibling without SCA from the same 2 parents. Families agreed to HLA antigen typing and transplantation if a matched sibling donor was identified or to standard care in the absence of a matched sibling donor.ExposuresMSD-HSCT (n = 32), compared with standard care (n = 35) (transfusions for ≥1 year with potential switch to hydroxyurea thereafter), using propensity score matching.Main outcomes and measuresThe primary outcome was the highest time-averaged mean of maximum velocities in 8 cerebral arteries, measured by TCD (TCD velocity) at 1 year. Twenty-five of 29 secondary outcomes were analyzed, including the highest TCD velocity at 3 years and normalization of velocities (<170 cm/s) and ferritin levels at 1 and 3 years.ResultsSixty-seven children with SCA (median age, 7.6 years; 35 girls [52%]) were enrolled (7 with stroke history). In the matched sample, highest TCD velocities at 1 year were significantly lower on average in the transplantation group (129.6 cm/s) vs the standard care group (170.4 cm/s; difference, -40.8 cm/s [95% CI, -62.9 to -18.6]; P < .001). Of the 25 analyzed secondary end points, 4 showed significant differences, including the highest TCD velocity at 3 years (112.4 cm/s in the transplantation group vs 156.7 cm/s in the standard care group; difference, -44.3 [95% CI, -71.9 to -21.1]; P = .001); normalization rate at 1 year (80.0% in the transplantation group vs 48.0% in the standard care group; difference, 32.0% [95% CI, 0.2% to 58.6%]; P = .045); and ferritin levels at 1 year (905 ng/mL in the transplantation group vs 2529 ng/mL in the standard care group; difference, -1624 [95% CI, -2370 to -879]; P < .001) and 3 years (382 ng/mL in the transplantation group vs 2170 ng/mL in the standard care group; difference, -1788 [95% CI, -2570 to -1006]; P < .001).Conclusions and relevanceAmong children with SCA requiring chronic transfusion because of persistently elevated TCD velocities, MSD-HSCT was significantly associated with lower TCD velocities at 1 year compared with standard care. Further research is warranted to assess the effects of MSD-HSCT on clinical outcomes and over longer follow-up.Trial registrationClinicalTrials.gov Identifier: NCT01340404.

Project description:Cerebral vasospasm in the first 2 weeks after aneurysmal subarachnoid hemorrhage is recognized as a major predictor of delayed cerebral ischemia. The routine screening for cerebral vasospasm with either transcranial Doppler or CT angiography has been advocated, although its diagnostic value has not yet been determined. Our study investigated the diagnostic accuracy of detecting vasospasm by transcranial Doppler and CT angiography for the prediction of delayed cerebral ischemia and functional outcome. Additionally, agreement between transcranial Doppler and CT angiography was determined.DesignProspective diagnostic accuracy study.SettingsNeurocritical care unit and neurosurgical ward at a tertiary academic medical center.PatientsBetween 2013 and 2016, 59 consenting patients were included.InterventionPatients undergo both transcranial Doppler and CT angiography for detection of cerebral vasospasm on days 5 and 10 after aneurysmal subarachnoid hemorrhage. Delayed cerebral ischemia was defined as secondary neurologic deterioration, not explained otherwise. Unfavorable outcome was defined modified Rankin Scale > 2 at 6 months.Measurements and main resultsOn transcranial Doppler, cerebral vasospasm was observed in 26 patients (45%). On CT angiography, vasospasm was observed in 54 patients (95%). The agreement between transcranial Doppler and CT angiography was 0.47. Delayed cerebral ischemia occurred in 16 patients (27%); unfavorable outcome in 12 patients (20%). Transcranial Doppler predicted delayed cerebral ischemia with a sensitivity of 0.44 (day 5) and 0.50 (day 10), with a specificity of 0.67 (day 5) and 0.57 (day 10). CT angiography predicted delayed cerebral ischemia with a sensitivity of 0.81 (day 5 and 10) and with a specificity of 0.070 (day 5) and 0.00 (day 10). The highest accuracy for predicting unfavorable outcome was on day 5 (0.61 for transcranial Doppler vs 0.27 for CT angiography).ConclusionThe diagnostic accuracy of both CT angiography and transcranial Doppler for detection of cerebral vasospasm as well as prediction of delayed cerebral ischemia and functional outcome is limited. The agreement between CT angiography and transcranial Doppler is low.

Dataset Information

Interleukin-10 haplotypes are not associated with acute cerebral ischemia or high-risk transcranial Doppler in a newborn cohort of 395 children with sickle cell anemia.

Publications

Interleukin-10 haplotypes are not associated with acute cerebral ischemia or high-risk transcranial Doppler in a newborn cohort of 395 children with sickle cell anemia.

Similar Datasets

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