Rachel Kesse-Adu

Low flow nocturnal oxygen therapy does not suppress haemoglobin levels or increase painful crises in sickle cell disease

15 antibodies using the two allelic variants of CD109. Again, the expected immunoreactivity was observed: both antiHPA-15b samples reacted against the HPA-15b variant (CD109, Y682) with little reactivity against HPA-15a (CD109, Y682; Fig 2F, G). Similarly, the two anti-HPA-15a samples showed stronger reactivity to HPA-15a than to HPA-15b (Fig 2H, I); the magnitude of the response again varied between individuals, as expected. Taken together, these data demonstrate that recombinant proteins that contain the epitopes responsible for HPA-5 and HPA-15 alloreactivity can be expressed in a format suitable for systematic screening in a clinical setting. These findings now provide an important proof-of-principle to develop a costeffective screening assay for these HPAs which are responsible for several rare but potentially life-threatening diseases.

Effect of N-acetylcysteine on pain in daily life in patients with sickle cell disease: a randomised clinical trial

N.J.S. collected and analysed the data and wrote the manuscript; H.K. designed the study and treated patients; E.J., J.E.C, D.A.T, M.E.R., N.D., Y.A., M.K., P.K., W.G.W. and C.D.D. treated patients; C.B., D.M. and M.A.R. collected and analysed the data; F.R. designed the study, collected and analysed the data, treated patients and wrote the manuscript. All authors approved the final version of the manuscript.

Intracranial Aneurysms in Sickle-Cell Disease Are Associated With the Hemoglobin SS Genotype But Not With Moyamoya Syndrome

Background and Purpose— Intracranial aneurysms and aneurysmal subarachnoid hemorrhage may occur more frequently in sickle-cell disease (SCD), and this could be related to the sickle genotype and moyamoya syndrome seen in SCD. Methods— Records from a total of 1002 patients with SCD attending 2 specialized adult hematologic services were retrospectively reviewed. We analyzed data of a cohort of 767 patients attending 1 SCD clinic between 2002 and 2013 and of 235 patients from the other clinic who have had neurovascular imaging between 2007 and 2014. Results— We identified 4 patients in the cohort who had an aneurysmal subarachnoid hemorrhage during 9063 patient-years. The highest incidence rate was seen among women in the age group 30 to 39 years with the hemoglobin SS (HbSS) genotype (440 per 100 000 patient-years). Unruptured intracranial aneurysms were found in 20 of the 324 patients, who had imaging data; the prevalence was significantly higher in patients with HbSS genotype compared with other sickle genotypes with the highest prevalence (15%) observed in women in the age group 30 to 39 years. Fifty-one HbSS patients had a moyamoya vasculopathy, but only 3 of these had concomitant intracranial aneurysms. Conclusions— Intracranial aneurysms are common in HbSS SCD. There was also a trend toward more common occurrence of aneurysmal subarachnoid hemorrhage in HbSS; women in the age group 30 to 39 years were most at risk. There was no correlation between the occurrence of intracranial aneurysms and moyamoya syndrome.

Cementless total hip replacements in sickle cell disease

Background Sickle cell disease (SCD) affects around 80,000 people in the USA and 12,000 in the UK. Up to 40% of patients will get osteonecrosis of the femoral head. Cemented acetabular components yield poor results with the rate of osteolysis ranging from 13.5 to 46%. We report on a consecutive cohort of patients with SCD who underwent uncemented THA with ceramic-on-ceramic (CoC) bearings. Methods Since 2002 52 primary THAs were carried out in 40 patients. The average age was 36.1 years (17-54). 48 cases had exchange blood transfusion preoperatively and 3 had top-up transfusions. An S-ROM was used in 47 hips a Solutions stem in 4 hips and an AML in 1. It was necessary to drill the femur during 12 hips. There were 5 intra-operative peri-prosthetic fractures. 2 dislocations were observed. 2 superficial infections were detected. Results All components have in-grown. There have been no cases of radiographic osteolysis, migration or loosening of the hip with average 5-year (2-10.1) follow-up. Conclusions The combination of a multidisciplinary team approach and uncemented implants, with ceramic-on-ceramic bearings used, has made THA in patients with SCD a safe and reliable procedure in our hospital.

White matter integrity and processing speed in sickle cell anemia

Objective The purpose of this retrospective cross-sectional study was to investigate whether changes in white matter integrity are related to slower processing speed in sickle cell anemia. Methods Thirty-seven patients with silent cerebral infarction, 46 patients with normal MRI, and 32 sibling controls (age range 8–37 years) underwent cognitive assessment using the Wechsler scales and 3-tesla MRI. Tract-based spatial statistics analyses of diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) parameters were performed. Results Processing speed index (PSI) was lower in patients than controls by 9.34 points (95% confidence interval: 4.635–14.855, p = 0.0003). Full Scale IQ was lower by 4.14 scaled points (95% confidence interval: −1.066 to 9.551, p = 0.1), but this difference was abolished when PSI was included as a covariate (p = 0.18). There were no differences in cognition between patients with and without silent cerebral infarction, and both groups had lower PSI than controls (both p < 0.001). In patients, arterial oxygen content, socioeconomic status, age, and male sex were identified as predictors of PSI, and correlations were found between PSI and DTI scalars (fractional anisotropy r = 0.614, p < 0.00001; r = −0.457, p < 0.00001; mean diffusivity r = −0.341, p = 0.0016; radial diffusivity r = −0.457, p < 0.00001) and NODDI parameters (intracellular volume fraction r = 0.364, p = 0.0007) in widespread regions. Conclusion Our results extend previous reports of impairment that is independent of presence of infarction and may worsen with age. We identify processing speed as a vulnerable domain, with deficits potentially mediating difficulties across other domains, and provide evidence that reduced processing speed is related to the integrity of normal-appearing white matter using microstructure parameters from DTI and NODDI.

AnaemiaInherited anaemias: sickle cell and thalassaemia

Inherited haemolytic anaemias are caused by a genetic mutation that results in an abnormality within the red cell leading to its early destruction. This abnormality may affect the cell membrane (e.g. hereditary spherocytosis), result from an absence or abnormality of a red cell enzyme (e.g. glucose-6-phosphate dehydrogenase deficiency) or affect haemoglobin, leading to a haemoglobinopathy such as sickle cell disease or thalassaemia.