Characteristics of Moyamoya Syndrome in Sickle-Cell Disease by Magnetic Resonance Angiography: An Adult-Cohort Study

Background: Sickle cell disease (SCD) can be complicated by moyamoya syndrome. Brain magnetic resonance angiography (MRA) is a non-invasive method to diagnose this syndrome and, steno-occlusion and moyamoya vessels (MMV) scores have been proposed to evaluate its severity. Previous studies of SCD moyamoya syndrome did not evaluate the severity according to MRA scores. The objective was to assess the characteristics of moyamoya syndrome in an adult cohort of SCD using these MRA scores.Methods: Twenty-five SCD patients with moyamoya syndrome were included using MRA with 3D time of flight technique. We evaluate steno-occlusion score for each hemisphere (range 0–10) from: steno-occlusion severity of internal carotid (ICA) (0–3), anterior cerebral (ACA) (0–3), middle cerebral (MCA) (0–2), and posterior cerebral (PCA) (0–2) arteries. MMV score for each hemisphere (range 0–5) depended from 5 MMV areas: (1) anterior communicating artery (2) basal ganglia (3) ICA/MCA (4) posterior communicating artery/PCA (5) basilar artery.Results: Eight patients (32%) showed unilateral moyamoya syndrome. ICA steno-occlusion was involved in 22 patients (88%), MCA in 23 patients (92%), ACA in 9 patients (36%), and PCA in 3 patients (12%). MMV involved ACoA area in 10 patients (40%), basal ganglia in 13 patients (52%), PCoA/PCA in 10 patients (40%), MCA/ICA in 7 patients (28%), and BA in 1 patient (4%). Steno-occlusion and MMV mean hemisphere scores were 3.4/10 (± 1.42) and 1.6/5 (± 0.71), respectively.Conclusion: Frequent unilateral moyamoya syndrome, uncommon PCA involvement and, moderate steno-occlusion and MMV scores seem to be features of SCD moyamoya syndrome. In future studies, MRA scores could be collected to assess the follow-up in these patients

A methodology to develop a vascular geometry for in vitro cell culture using additive manufacturing

Today, additive manufacturing (AM) is implemented in medical industry and profoundly revolutionizes this area. This approach consists of producing parts by additions of layers of successive materials and offers advantages in terms of rapidity, complexity of parts, competitive costs that can be exploited and can lead to a significant advancement in biological research. Everything becomes technically feasible and gives way to a “techno-centered” approach. Many parameters must be controlled in this field, so it is necessary to be guided for the development of such a product. This article aims to present a state of the art of existing design methodologies focused on AM to create medical devices. Finally, a development method is proposed that consists of producing vascular geometry using AM, based on patient data, designed for cell culture in vitro studies

Effects of corticosteroids in patients with sickle cell disease and acute complications: a systematic review and meta-analysis

Whether corticosteroids improve outcome in patients with acute complications of sickle cell disease (SCD) is still debated. We performed a systematic review of the literature with the aim of estimating effects of corticosteroids on the clinical course of vaso-occlusive crisis (VOC) or acute chest syndrome (ACS) in patients with SCD. The primary outcome was transfusion requirement during hospitalization. Studies were identified by search of MEDLINE and CENTRAL database. Three randomized clinical trials (RCT) and three retrospective cohort studies (RCS) were included, involving 3,304 participants and 5,562 VOC or ACS episodes. There was no difference between corticosteroids and standard treatment regarding transfusion requirement overall (odds ratio [OR]=0.98, 95% confidence interval [CI]: 0.38-2.53) but there was a significant interaction of the study type (P<0.0001): corticosteroid therapy was associated with a lower risk of transfusion in RCT (OR=0.13, 95% CI: 0.04-0.45) and a higher risk of transfusion in RCS (OR=2.12, 95% CI: 1.33-3.40. In RCT, the length of hospital stay was lower with corticosteroids as compared with standard treatment: mean difference - 24 hours (95% CI: -35 to -14). Corticosteroids were associated with an increased risk of hospital readmission as compared with standard treatment, in RCT, RCS, and the entire cohort: OR=5.91, 95% CI: 1.40-24.83; OR=3.28, 95% CI: 1.46-7.36 and OR=3.21, 95% CI: 1.97-5.24, respectively. Corticosteroids were associated with reduced number of transfusions and length of stay in RCT but not in RCS, with more rehospitalizations overall. Additional RCT should be conducted while minimizing the risk of rehospitalizations

First evidence of subclinical renal tubular injury during sickle-cell crisis

International audienceBACKGROUND: The pathophysiologic mechanisms classically involved in sickle-cell nephropathy include endothelial dysfunction and vascular occlusion. Arguments demonstrating that ischemia-reperfusion injury-related kidney damage might coincide with vaso-occlusive crisis (VOC) are lacking. METHODS: In this prospective study, we sought to determine whether tubular cells and glomerular permeability might be altered during VOC. Urine neutrophil gelatinase-associated lipocalin (NGAL) levels and albumin-excretion rates (AER) of 25 patients were evaluated prospectively during 25 VOC episodes and compared to their steady state (ST) values. RESULTS: During VOC, white blood-cell counts (WBC) and C-reactive protein (CRP) were significantly higher than at ST but creatinine levels were comparable. Urine NGAL levels were significantly increased during VOC vs ST (P = 0.007) and remained significant when normalized to urine creatinine (P = 0.004), while AER did not change significantly. The higher urine NGAL concentration was not associated with subsequent (24-48 hour) acute kidney injury. Univariate analysis identified no significant correlations between urine NGAL levels and laboratory parameters during VOC. CONCLUSIONS: These results demonstrated that subclinical ischemia-reperfusion tubular injury is common during VOC and highlight the importance of hydroelectrolyte monitoring and correction during VOC

Gene-metabolite annotation with shortest reactional distance enhances metabolite genome-wide association studies results

Metabolite genome-wide association studies (mGWAS) have advanced our understanding of the genetic control of metabolite levels. However, interpreting these associations remains challenging due to a lack of tools to annotate gene-metabolite pairs beyond the use of conservative statistical significance threshold. Here, we introduce the shortest reactional distance (SRD) metric, drawing from the comprehensive KEGG database, to enhance the biological interpretation of mGWAS results. We applied this approach to three independent mGWAS, including a case study on sickle cell disease patients. Our analysis reveals an enrichment of small SRD values in reported mGWAS pairs, with SRD values significantly correlating with mGWAS p values, even beyond the standard conservative thresholds. We demonstrate the utility of SRD annotation in identifying potential false negatives and inaccuracies within current metabolic pathway databases. Our findings highlight the SRD metric as an objective, quantitative and easy-to-compute annotation for gene-metabolite pairs, suitable to integrate statistical evidence to biological networks

Contribution of fetal microchimeric cells to maternal wound healing in sickle cell ulcers

Leg ulcers are a major complication of sickle cell disease (SCD). They are particularly challenging to treat and innovative therapies are needed. We previously showed that the healing of SCD ulcers is delayed because of decreased angiogenesis. During pregnancy, fetal microchimeric cells (FMC) transferred to the mother are recruited to maternal wounds and improve angiogenesis. After delivery, FMC persist in maternal bone marrow for decades. Here, we investigated whether fetal cells could also improve SCD ulcers in the post-partum setting. We found that skin healing was similarly improved in post-partum mice and in pregnant mice, through increased proliferation and angiogenesis. In a SCD mouse model that recapitulates refractory SCD ulcers, we showed that the ulcers of post-partum SCD mice healed more quickly than those of virgin mice. This was associated with the recruitment of fetal cells in maternal wounds where they harbored markers of leukocytes and endothelial cells. In a retrospective cohort of SCD patients, using several parameters we found that SCD women who had ever had a baby had less of a burden related to leg ulcers compared to nulliparous women. Taken together, these results indicate that healing capacities of FMC are maintained long after delivery and may be exploited to promote wound healing in post-partum SCD patients

Endurance training improves oxygen uptake/demand mismatch, metabolic flexibility and recovery in patients with sickle cell disease

Patients with sickle cell disease (SCD) display lower slope coefficients of the oxygen uptake (V_O2) vs. work rate (W) relationship (delineating an O2 uptake/demand mismatch) and a poor metabolic flexibility. Because endurance training (ET) increases the microvascular network and oxidative enzymes activity including one involved in lipid oxidation, ET might improve the slope coefficient of the V_O2 vs. W curve and the metabolic flexibility of SCD patients. ET may also contribute to improve patient post-exercise cardiopulmonary and metabolic recovery. Fifteen patients with SCD performed a submaximal incremental test on a cycle ergometer before (SIT1) and after (SIT2) 8 weeks of ET. Minute ventilation, ventilation rate (VR), heart rate (HR), V_O2, CO2 production, respiratory exchange ratio, carbohydrate/lipid utilization and partitioning (including %Lipidox) and blood lactate concentration ([lactate]b) were measured during and after SIT1 and SIT2. At baseline, the slope coefficient of the V_O2 vs. W curve positively correlated with total hemoglobin, mean corpuscular hemoglobin and percentage of HbF. After training, the slope coefficient of the V_O2 vs. W curve was significantly higher and the [lactate]b increase was delayed. If patients’ energy metabolism apparently relied largely on carbohydrate sources during SIT1, %Lipidox tended to increase at low exercise intensities during SIT2, supporting a training-induced improvement of metabolic flexibility in patients with SCD. Post-exercise recovery of VR, V_E/V_CO2, HR and [lactate]b was faster after training. We concluded that ET in patients with SCD i) ameliorated the oxygen uptake/demand mismatch, ii) blunted the metabolic inflexibility, and iii) improved post-exercise cardiopulmonary and metabolic responses