Time-averaged Mean Velocity Research Articles

Pattern of Cerebral Blood Flow Velocity Using Transcranial Doppler Ultrasonography in Children with Sickle Cell Disorder in Lagos State, Nigeria.

Cerebrovascular accident (CVA) is a common, devastating neurological complication of sickle cell disorder (SCD) with a high recurrent and mortality rate. The Stroke Prevention Trial in Sickle Cell Anaemia study (STOP) recommends routine screening with transcranial Doppler ultrasonography in children aged two to sixteen years with SCD. The present study assessed cerebral blood flow velocities of children with SCD in accordance with the recommendation of routine screening by the STOP study.MethodsTranscranial Doppler ultrasonography was done for children with SCD that attended Sickle Cell Foundation, Nigeria between July and November 2015.ResultsIn all, 388 subjects were screened within the study period (360 HbSS and 28 HbSC). The prevalence of abnormal Time-Averaged Maximum Mean Velocity (TAMMV) of at least 200 cm/second was 10.8%: this was seen solely in HbSS subjects. The mean Time-averaged mean of the maximum (TAMM) velocity were 163±25 cm/sec, 162±30 cm/sec and 150±30 cm/sec for children less than five years, five to ten years and eleven to sixteen years respectively.ConclusionThe prevalence of abnormal TAMM velocity in children with HbSS is 10.8%. Identification of subjects at risk helped in primary CVA prevention by prompt therapy institution.

Evaluation of arterial digital blood flow using Doppler ultrasonography in healthy dairy cows

BackgroundLocal circulatory disturbances have been implicated in the development of foot disorders in cattle. The goals of this study were to evaluate the suitability of the interdigital artery in the pastern region in both hind limbs using pulsed-wave (PW) Doppler ultrasonography and to investigate quantitative arterial blood flow variables at that site in dairy cows. An Esaote MyLabOne ultrasound machine with a 10-MHz linear transducer was used to assess blood flow in the interdigital artery in the pastern region in both hind limbs of 22 healthy German Holstein cows. The cows originated from three commercial farms and were restrained in a standing hoof trimming chute without sedation.ResultsA PW Doppler signal suitable for analysis was obtained in 17 of 22 cows. The blood flow profiles were categorised into four curve types, and the following quantitative variables were measured in three uniform cardiac cycles: vessel diameter, pulse rate, maximum systolic velocity, maximum diastolic velocity, end-diastolic velocity, reverse velocity, maximum time-averaged mean velocity, blood flow rate, resistance index and persistence index. The measurements did not differ among cows from the three farms. Maximum systolic velocity, vessel diameter and pulse rate did not differ but other variables differed significantly among blood flow profiles.ConclusionsDifferences in weight-bearing are thought to be responsible for the normal variability of blood flow profiles in healthy cows. The scanning technique used in this report for evaluation of blood flow in the interdigital artery appears suitable for further investigations in healthy and in lame cows.

Stroke prevention in sickle cell disease – The role of cervical echo-doppler

Objective: Cerebrovascular disease is the main cause of mortality and chronic morbidity in pediatric sickle cell disease (SCD) patients. Systematic screening using transcranial doppler (TCD) stratifies the risk of stroke and allows effective primary prevention. The role of cervical vasculopathy remains unclear and some patients present stroke events with normal TCD. Methods: In this retrospective study we included all children/adolescents with HbSS, HbSC or HbSβ0 and at least one appointment in our Pediatric Hematology clinic from January 2013 to December 2015. After 2 years old, they performed TCD and cervical echo-doppler and attended a Pediatric Neurology appointment, according to our Cerebrovascular Prevention Program. We collected patient's information regarding: demographic data, therapy, stroke history, neurological exam, last cranial and cervical echo-doppler and cranial MRI results. Results: A total of 110 patients were included with median age of 10. From the group of 102 patients older than 2 years, 98 (96%) have at least one TCD. In the last TCD, only 1 (1%) had a time-averaged maximum mean (TAMM) velocity ≥ 200 cm/sec and 4 (4%) had velocities in the conditional range (170–199 cm/sec). Thirty-six patients (33%) performed cranial MRI, 16 (44%) had vascular pathological findings – 6 stroke, 10 silent cerebral infarcts (5 isolated), 6 intracranial stenosis or moya–moya pattern and 3 other changes. Six patients (5.5%) had a stroke (5 ischemic and 1 hemorrhagic), 5 with normal TCD but 5 with abnormal cervical doppler velocities. In the last years the clinical presentation of ischemic strokes (2) was mild limb paresis diagnosed in the pediatric neurology appointment, in patients with normal TCD, abnormal cervical echo-doppler and evidence of cranial vasculopathy in MRI. Conclusion: More studies are needed to clarify the role of cervical vasculopathy in cerebrovascular disease and the best prevention treatment in patients with abnormal cervical echo-doppler remains unclear.

A comparison of haemodynamics between subcranial-intracranial bypass and the traditional extracranial-intracranial bypass

Background: Ischemic cerebrovascular diseases are traditionally treated using an extracranial-intracranial (EC-IC) bypass. The use of the internal maxillary artery (IMA) in the subcranial-intracranial (SC-IC) bypass was recently described as an alternative treatment. However, the haemodynamics of this new approach have not been defined.Methods: The haemodynamic parameters (flow volume [FV], internal diameter [ID], time-averaged mean velocity [TAM], pulsatility index [PI] and resistance index [RI]) of the IMA-radial artery graft (RAG)-middle cerebral artery (MCA) (n = 12) bypass and superficial temporal artery (STA)-MCA bypass (n = 18) were measured using intraoperative duplex ultrasonography and compared.Results: The FV was 81.36 ± 30.41 (62.05–100.70) ml/min for the IMA-RAG-MCA bypass. This was significantly higher than that of the STA-MCA bypass (27.25 ± 9.32 (22.62–31.88) ml/min; P < .01). The ID and TAM in the IMA-RAG-MCA bypass were higher than in the STA-MCA bypass (P < .01; P < .01). No significant differences were observed in PI (P ≈ .21) and RI (P ≈ .08). The early patency rate (one month after the operation) was 100% for the IMA-RAG-MCA bypass and 94% for the STA-MCA bypass.Conclusions: The IMA-RAG-MCA bypass provides moderate to high blood flow to the revascularized territory and blood flow was higher by this method than the STA-MCA bypass.

Lower Transcranial Doppler Flow Velocities in Sickle Cell Anemia Patients on Hydroxyurea: Myth or Fact.

Transcranial Doppler (TCD) detects stroke risk in patients with sickle cell anemia (SCA). Hydroxyurea therapy has the ability to induce increased levels of fetal hemoglobin in sickle cells thus decreasing tendency for red cell sickling. This study aimed to evaluate TCD findings in SCA patients on hydroxyurea and correlate the time-averaged mean velocity (TAMV) with their hematological parameters. Forty SCA patients of both sexes, aged 16-22years with no history of stroke were screened with TCD for an elevated TAMV, divided into: Group T (20 patients on blood transfusion); and Group H (20 patients on daily hydroxyurea). For all, full medical history, clinical examination, hemoglobin, hematocrit, leukocytes, platelets, fetal hemoglobin and sickling test, in addition TCD to describe the pattern of cerebral blood flow abnormalities were done. TAMV in all cerebral arteries were significantly higher in Group T than Group H, the highest TAMV (147.5±57.09cm/s) was found in the right middle cerebral artery and correlated negatively with hematocrit in Groups H (P<0.001). There were 2 (10%) abnormal TAMV results and 5 (25%) conditional in Group T, while all results were normal in Group H. Hydroxyurea therapy may lower TCD velocities and prevent the risk of primary stroke in SCA patients.

Test-Retest Reliability of Measuring the Vertebral Arterial Blood Flow Velocity in People With Cervicogenic Dizziness

ObjectivesThe purpose of this study was to determine the within-session and between-sessions reliability of measuring the vertebral artery blood flow velocities in people with cervicogenic dizziness using Doppler ultrasound at both upper and lower cervical levels. MethodsOutcome measures were taken on 2 occasions 3 weeks apart with no active treatment provided in between the assessments on 12 participants. Pulsed-wave Doppler ultrasound was used to quantify time-averaged mean velocities through the vertebral artery at upper cervical (C0-1) and lower cervical vertebrae (C5-6). The clinical outcome measures were also recorded in people with cervicogenic dizziness. The intraclass correlation coefficient (ICC) was used to determine the within-session and between-session repeatability. Paired t test was used to determine the differences in the time-averaged mean velocities of blood flow at the same site of the vertebral artery and the clinical outcome measures in 2 sessions 3 weeks apart. ResultsIn people with cervicogenic dizziness, there was no significant change in both clinical outcome measures and the time-averaged mean velocities when the patients were measured 3 weeks apart (P > .05). This study identified good within-session (ICC: 0.903-0.967) and between-session (ICC: 0.922-0.984) repeatability in measuring the vertical blood flow velocities in patients with cervicogenic dizziness when the clinical outcome measures were unchanged. ConclusionsThis study supports the use of Doppler ultrasound to identify changes in mean vertebral arterial blood flow velocities before and after intervention in people with cervicogenic dizziness in future studies.

Transcatheter aortic valve implantation improves carotid and vertebral arterial blood flow in patients with severe aortic stenosis: practical role of orthostatic stress test.

There are no data on the impact of transcatheter aortic valve implantation (TAVI) on carotid and vertebral arterial blood flow. Our aim was to assess the effects of the orthostatic stress test on carotid and vertebral artery blood flow in patients with severe aortic stenosis (AS) undergoing TAVI. TAVI may have beneficial effect on carotid and vertebral artery flow in patients with severe aortic stenosis. Thirty carefully selected patients with severe AS undergoing TAVI were enrolled. Peak systolic blood-flow velocity and end-diastolic velocity in the common carotid artery, internal carotid artery, and vertebral artery, as well as spectral analysis of flow pattern with time-averaged maximum velocity (centimeters per second), time-averaged mean velocity (centimeters per second), and flow volume (milliliters per minute) on both sides were measured by duplex ultrasound. Measurements were performed in the supine position and at 1 to 2 minutes after the assumption of the standing position at baseline and 3 months after TAVI. All duplex ultrasound parameters assessed in the supine position have significantly improved in patients after TAVI as compared to baseline (P < 0.001 for all). The orthostatic stress test induced decrease of carotid and vertebral arterial flow velocities in AS patients before and after TAVI. However, the drop in velocities and flow volume was numerically lower after TAVI. TAVI may have some beneficial effect on extracranial artery blood flow by minimalization of its decrease as a response to orthostatic stress.

Randomised Controlled Trial: Potential Benefit of a Footplate Neuromuscular Electrical Stimulation Device in Patients with Chronic Venous Disease

Chronic venous disease (CVD) is common, affecting a quarter of the population. Current conservative methods of treatment aim to prevent progression of disease by reducing ambulatory venous pressure. Neuromuscular electrical stimulation (NMES) refers to the use of electrical impulses to elicit muscle contraction. This pilot randomised controlled trial investigates the effect of a footplate NMES device (REVITIVE) on venous flow parameters, limb oedema, and quality of life outcome measures in patients with CVD. Twenty-two patients with Clinical Etiological Anatomical and Pathophysiological (CEAP) clinical class C2–C4 venous disease were randomised to receive a sham or test device. The recommended duration of use was for 30 minutes daily for 6 weeks. Venous flow parameters (duplex ultrasound), limb volume (optoelectric volumeter), and quality of life outcome measures were measured at baseline and after 6 weeks. The mean age of participants was 62 years, body mass index 28.6, with a 15:7 female preponderance. There was a significant difference in the percentage change in femoral vein flow parameters (from baseline) between the test and sham group while using the device (Week 0 time-averaged mean velocity 102.4% vs. −9.1%, p < .0001; volume flow 107.9% vs. −3.7%, p < .0001; peak velocity 377.7% vs. −6.7%, p < .0001). Limb volume was observed to increase significantly in the sham group (2.0% at Week 0 and 1.2% at Week 6; p < .01). This was prevented in the test group (+0.8% at Week 0 and 1.0% at Week 6; p = .06). There was a significant difference in the Aberdeen Varicose Vein Questionnaire between the two groups over the 6 weeks. This trial demonstrated a significant difference in venous flow parameters and prevention of orthostatic limb oedema with NMES. There was a positive effect on quality of life. Larger studies are required to determine the clinical significance of this in patients with venous disease.

Laboratory and Genetic Biomarkers Associated with Cerebral Blood Flow Velocity in Hemoglobin SC Disease.

Reference values for cerebral blood flow velocity (CBFV) in hemoglobin SC disease (HbSC) have not been established. We aimed to investigate associations between laboratory and genetic biomarkers associated with CBFV in HbSC children. Sixty-eight HbSC children were included; CBFV was analyzed by transcranial Doppler, and the time-averaged maximum mean velocity (TAMMV) was estimated. Hematological, biochemical, immunological, and genetic analyses were performed. TAMMV was negatively correlated with red blood cell count (RBC) count, hemoglobin, hematocrit, and direct bilirubin (DB), yet positively correlated with monocytes and ferritin. We found that children with TAMMV ≥ 128 cm/s had decreased red blood cell distribution width (RDW) and nitric oxide metabolite (NOx) concentration. Children with TAMMV ≥ 143.50 cm/s had decreased hemoglobin and hematocrit, as well as increased ferritin levels. Decreased hemoglobin, hematocrit, RDW, and NOx and increased ferritin were detected in children with TAMMV ≥ 125.75 cm/s. The CAR haplotype was associated with higher TAMMV. In association analyses, RBC, hemoglobin, hematocrit, RDW, monocyte, DB, NOx, and ferritin, as well as the CAR haplotype, were found to be associated with higher TAMMV in HbSC children. Multivariate analysis suggested that high TAMMV was independently associated with hematocrit, RDW, and NOx. Additional studies are warranted to validate the establishment of a cutoff value of 125.75 cm/s associated with elevated TAMMV in HbSC children.

Transcranial Doppler in hemoglobin SC disease.

Stroke is a severe clinical disorder in sickle cell disease (SCD), and few studies have evaluated transcranial Doppler (TCD) flow velocities in hemoglobin SC disease (HbSC). The guidelines for stroke risk are based on evaluations in sickle cell anemia (SCA) or HbS/β thalassemia. In this study, we compare cerebral blood flow in patients with SCD stratified by genotypes. A total of 1,664 pediatric patients with SCD underwent TCD velocity screening, and the time-averaged maximum mean velocity (TAMM) was determined in the middle cerebral artery (MCA), anterior cerebral artery (ACA), and distal intracranial internal carotid artery (ICA). Abnormal velocities were not identified in the ACA; therefore, we only use ICA and MCA velocities. TAMM from the left and right in the ICA and MCA was 134.3 ± 32.0 and 134.4 ± 32.6 cm/s in patients with SCA, and 105.2 ± 20.6 and 104.7 ± 20.0 cm/s in the patients with HbSC, respectively. Mean TAMM between right and left ICA/MCA was 134.5 ± 30.5 cm/s in the SCA group, and 104.9 ± 19.3 cm/s in the HbSC group. Notably, our data show that TCD velocities were significantly lower among the patients with HbSC compared to SCA. TAMM was negatively correlated with hemoglobin and hematocrit in both genotypes. These results suggest that a different cut-off value for abnormal TCD velocities could be considered for patients with HbSC. Additional studies are warranted to determine the actual risk of stroke in HbSC genotype associated with this possible TCD risk value.

Dynamic response of cerebral perfusion during low-intensity cycling exercise: A study using transcranial Doppler ultrasound

&lt;p&gt;&lt;tt&gt;We investigated the changes in cerebral perfusion during constant low-intensity exercise and the effect of a late increase in workload. Eleven healthy males participated in this study. Four subjects performed 15 min of constant low-intensity exercise on a cycle ergometer, while seven subjects performed 20 min of exercise consisting of 17 min of low-intensity exercise, which was incremented to moderate-intensity for the final 3 min. As an index for cerebral perfusion, the time-averaged mean velocity of flow in the middle cerebral artery (MCAV&lt;sub&gt;mean&lt;/sub&gt;) was measured using transcranial Doppler ultrasound. During the 15-min of low-intensity exercise (78 ± 3 Watts), pulmonary oxygen consumption (&lt;em&gt;V&lt;/em&gt;O&lt;sub&gt;2&lt;/sub&gt;) increased to 19.1 ± 2.5 ml/min/kg within 3-6 min, while &lt;/tt&gt;end-tidal pressure of carbon dioxide (P&lt;sub&gt;ET&lt;/sub&gt;CO&lt;sub&gt;2&lt;/sub&gt;) increased to &lt;tt&gt;42.0 ± 3.2 mmHg, and MCAV&lt;sub&gt;mean&lt;/sub&gt; increased to a peak 19.2 ± 9.1 % above the pre-exercise resting level then gradually decreased back toward the resting level. During the 20-min exercise at low and then moderate intensity &lt;/tt&gt;(77 &lt;tt&gt;± 4 and &lt;/tt&gt;111 &lt;tt&gt;± 7 Watts for low and moderate intensity, respectively), &lt;em&gt;V&lt;/em&gt;O&lt;sub&gt;2&lt;/sub&gt; increased from 19.1 ± 2.8 to 24.2 ± 3.6 ml/min/kg after the late increment in exercise intensity, while&lt;/tt&gt; P&lt;sub&gt;ET&lt;/sub&gt;CO&lt;sub&gt;2&lt;/sub&gt; remained unchanged (&lt;tt&gt;p = 0.48, Tukey’s post hoc test&lt;/tt&gt;), and &lt;tt&gt;MCAV&lt;sub&gt;mean&lt;/sub&gt; tended to increase but did not change significantly. K&lt;/tt&gt;inetic analysis of &lt;em&gt;V&lt;/em&gt;O&lt;sub&gt;2&lt;/sub&gt; and &lt;tt&gt;MCAV&lt;sub&gt;mean&lt;/sub&gt;&lt;/tt&gt; at low and moderate exercise intensities &lt;tt&gt;using a monoexponential model revealed that the &lt;/tt&gt;time constant (τ) for &lt;em&gt;V&lt;/em&gt;O&lt;sub&gt;2&lt;/sub&gt; was significantly related to the τ for &lt;tt&gt;MCAV&lt;sub&gt;mean&lt;/sub&gt;&lt;/tt&gt; at low (n=9) (R&lt;sup&gt;2 &lt;/sup&gt;=0.52, P =0.03) and moderate intensity (n=6) (R&lt;sup&gt;2&lt;/sup&gt; = 0.69, P =0.04). These findings imply that cardiac output exerts an indirect effect to alter cerebral perfusion and that cerebral autoregulation likely operates to stabilize cerebral blood flow during prolonged exercise at a constant workload.&lt;/p&gt;

Variation in Serial TCD Velocity Measurements in the TCD with Transfusions Changing to Hydroxyurea (TWiTCH) Trial

▪Introduction: The multicenter phase 3 randomized clinical trial TCD With Transfusions Changing to Hydroxyurea (TWiTCH, NCT01425307) investigated whether hydroxyurea could maintain TCD velocities and prevent stroke in children with sickle cell anemia and abnormal TCD velocities. The trial was stopped early after reaching the primary endpoint, when the average TCD velocity in the alternative (hydroxyurea) arm was found to be non-inferior and even slightly better (138 versus 143 cm/sec) than the standard (transfusion) arm. A planned secondary analysis was to determine the variation in serial TCD velocity measurements for individual study participants, to document the normal TCD velocity fluctuations that occur and to inform the need for frequent TCD evaluations in this clinical setting.Methods: All TCD examinations collected in TWiTCH were analyzed for the maximum time-averaged mean velocity (TAMV) measured in the main intracranial arteries. TCD studies were performed by certified examiners using identical non-imaging instruments, no more than one week before a scheduled transfusion or phlebotomy procedure. Measurements on the index side, defined as the cerebral hemisphere with the higher mean arterial velocity at baseline assessment, were used for these statistical analyses. TCD values were analyzed according to four phases of the trial: (1) screening with three monthly TCD examinations performed at Weeks -8, -4, and 0 before randomization; (2) initial treatment period (hydroxyurea dose escalation with overlap transfusions or transfusions only) with three quarterly TCD measurements at Weeks 12, 24, and 36; (3) steady-state treatment period (hydroxyurea only or transfusions only) with four quarterly TCD measurements at Weeks 48, 60, 72, and 84; and (4) study exit with three monthly TCD examinations performed at Weeks 96, 100, and 104 or during the accelerated close-out period. The within-patient variance and standard deviation of the TAMV values were found using a linear mixed model, which was calculated using SAS Version 9.3.Results: TAMV measurements on the index side from 1458 TCD examinations on 121 randomized patients formed the overall dataset. TAMV values ≥170 cm/sec were identified in 140 measurements on 40 children (9.6% of TCD values) and exceeded 200 cm/sec in 1.8% of examinations (26 values, 8 children) during the study treatment phase. The within-patient TCD variation, representing fluctuation of repeated TCD measurements in the same study participant, was 12.0 cm/sec for the entire cohort during the initial screening phase (363 TCD measurements). In the initial treatment phase, TCD variation in the hydroxyurea arm (180 values, 60 children) was 10.5 cm/sec, similar to 10.2 cm/sec on the transfusion arm (183 values, 61 children). In the steady-state treatment phase, the TCD variation in the hydroxyurea arm was 10.2 cm/sec (207 values, 57 children), compared to 12.3 cm/sec on the transfusion arm (212 values, 58 children). In the final exit phase, TCD variation in the hydroxyurea arm was 9.8 cm/sec (155 values, 58 children), similar to 10.2 cm/sec on the standard arm (155 values, 57 children). TCD variation was greater with higher baseline TCD velocity and shorter transfusion duration, but was not affected by age or gender. For example, participants with baseline TCD velocity of <170 cm/sec had a post-randomization measurement variation of 10.8 cm/sec, while those ≥170 cm/sec had higher variation (13.7 cm/sec, p=0.001).Conclusions: The TWiTCH trial provides prospective data regarding the biological variation in serial TCD values that occurs in children with previous abnormal TCD examinations but no severe vasculopathy. The observed within-patient variation in TCD velocities was consistently 10-14 cm/sec, with higher variation observed in children with higher baseline TCD velocities. This fluctuation can be expected with serial TCD examinations and should be considered before making treatment decisions based on a single TCD measurement. Since comparison of entry and exit TCD values in the TWiTCH trial documented that hydroxyurea at maximum tolerated dose was non-inferior to transfusions, frequent TCD examinations may not be warranted. DisclosuresWare:Bayer Pharmaceuticals: Consultancy; Addmedica: Research Funding; Global Blood Therapeutics: Consultancy; Bristol Myers Squibb: Research Funding; Biomedomics: Research Funding; Nova Laboratories: Consultancy. Heeney:Eli Lilly and Company: Research Funding; Pfizer: Research Funding; Sancilio and Company: Consultancy, Research Funding. Thompson:Baxalta (now part of Shire): Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Mast: Research Funding; Eli Lily: Research Funding; Celgene: Research Funding; Amgen: Research Funding; ApoPharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; bluebird bio: Consultancy, Research Funding.

Randomised Controlled Trial: Potential Benefit of a Footplate Neuromuscular Electrical Stimulation Device in Patients with Chronic Venous Disease

Chronic venous disease (CVD) is common, affecting a quarter of the population. Current conservative methods of treatment aim to prevent progression of disease by reducing ambulatory venous pressure. Neuromuscular electrical stimulation (NMES) refers to the use of electrical impulses to elicit muscle contraction. This pilot randomised controlled trial investigates the effect of a footplate NMES device (REVITIVE) on venous flow parameters, limb oedema, and quality of life outcome measures in patients with CVD. Twenty-two patients with Clinical Etiological Anatomical and Pathophysiological (CEAP) clinical class C2-C4 venous disease were randomised to receive a sham or test device. The recommended duration of use was for 30minutes daily for 6 weeks. Venous flow parameters (duplex ultrasound), limb volume (optoelectric volumeter), and quality of life outcome measures were measured at baseline and after 6 weeks. The mean age of participants was 62 years, body mass index 28.6, with a 15:7 female preponderance. There was a significant difference in the percentage change in femoral vein flow parameters (from baseline) between the test and sham group while using the device (Week 0 time-averaged mean velocity 102.4% vs.-9.1%, p<.0001; volume flow 107.9% vs.-3.7%, p<.0001; peak velocity 377.7% vs.-6.7%, p<.0001). Limb volume was observed to increase significantly in the sham group (2.0% at Week 0 and 1.2% at Week 6; p<.01). This was prevented in the test group (+0.8% at Week 0 and 1.0% at Week 6; p=.06). There was a significant difference in the Aberdeen Varicose Vein Questionnaire between the two groups over the 6 weeks. This trial demonstrated a significant difference in venous flow parameters and prevention of orthostatic limb oedema with NMES. There was a positive effect on quality of life. Larger studies are required to determine the clinical significance of this in patients with venous disease.

Laboratorial and Genetic Biomarkers Associated to Cerebral Blood Flow Velocity on Hemoglobin SC Disease

INTRODUCTIONClinical complications in hemoglobin SC disease (HbSC) are mild compared to sickle cell anemia (SCA), the most severe type of sickle cell disease. However, HbSC individuals have 100 times greater risk of stroke compared to the healthy population. The lack of studies to determine reference values for transcranial Doppler (TCD) velocities in HbSC is still a limitation considering that we have been used TCD velocities previously determined for the SCA and having as standard the one described by Adams et al. (1992). Other studies described cerebral blood flow velocities (CBFV) for HbSC individuals, and considered as abnormal values that exceed 128 cm/s and 143.5 cm/s respectively. Studies show the association of abnormal TCD with distinct laboratorial biomarkers, despite the controversial results. To our knowledge, there are no published studies based on specific biomarkers and abnormal CBFV for HbSC individuals. Thus, we aim to investigate the association of genetic, hematological and biochemical data with CBFV in HbSC. METHODSA cross-sectional study comprising 68 HbSC individuals, with an average age of 6.96 ± 3.90 years, whom 40 (58.82 %) were female, attended the Pediatric Cerebrovascular Disease Outpatient Center at the Hospital Universitario Professor Edgar Santos (HUPES) of the Universidade Federal da Bahia (UFBA) was conducted. All procedures were in accordance with the 1964 Helsinki declaration and its later amendments. The CBFV was estimated with TCD, and the time-averaged maximum mean velocity (TAMMV) in the middle cerebral arteries, anterior cerebral artery and distal intracranial internal carotid was assessed. Hematological and biochemical parameters, nitric oxide (NO) measurement and genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) 677C>T (rs1801133), vascular cell adhesion molecule (VCAM)-833T>C (rs1041163)and VCAM 1238G>C genes, α3.7Kb thalassemia (-α3.7-thal) and Beta S (βS) haplotypes were investigated. Statistical analyses were performed using SPSS version 18.0 software, Graphpad Prism version 6.0 and JMP software. P values <0.05 were considered significant. RESULTSThe median of TAMMV in the HbSC individuals was 111.50 cm/s, the 25th percentile was 101.50 cm/s and the 75th percentile was 125.75 cm/s. The TAMMV was negatively correlated to red blood cells (RBC) (R= -0.2734; P= 0.0315), hemoglobin (Hb) (R= -0.3390; P= 0.0070), hematocrit (Ht) (R= -0.3470; P= 0.0057) and direct bilirubin (R= -0.2545; P= 0.0363) and positively correlated to monocytes (R= 0.2533; P= 0.0470) and ferritin (R= 0.3044; P= 0.0145). Based on previous protocol for SCA established by Adams and colleagues, we found two individuals with low TCD, 64 with normal TCD, one with abnormal TCD and one with inconclusive TCD. Noteworthy, this classification is not suitable for HbSC individuals. Using a cut off value of 128 cm/s, defined by Deane and colleagues (2008), we found significant decreased RDW (p=0.035) and NO (p=0.017) values in HbSC individuals with TAMMV higher than 128 cm/s. Vieira and colleagues (2014) defined a cut off value of 143.50 cm/s for HbSC individuals in the same population of this study. We found significant decrease of Hb (p=0.008) and Ht (p=0.008) concentration and increased ferritin levels (p=0.023) in HbSC individuals with TAMMV higher than 143.50 cm/s. Value of TAMMV at 75th percentile (125.75 cm/s) was used in order to evaluate the laboratorial markers. We found significant differences in Hb, Ht, RDW and NO levels, which were decreased, and in the ferritin, which was elevated in HbSC individuals with TAMMV above 125.75 cm/s (Table 1). The multivariate analysis adjusted by age and sex showed that Ht (< 33.35%), RDW (> 15.55%) and NO (< 29.86 uM) were independently associated with TAMMV values higher than 125.75 cm/s (75th percentile) (Table 2). CONCLUSIONSWe suggest that RBC, Hb, Ht, RDW, monocyte, direct bilirubin, NO, ferritin, polymorphism on the MTHFR 677C>T gene and the absence of α3.7Kb thalassemia are associated with TAMMV on HbSC individuals. The TAMMV 125.75cm/s is lower than the those proposed by Deane et al. (2008) and Vieira et al. (2014), but have shown to be associated with hematological and biochemical changes found in both velocities 128 cm/s and 143.50 cm/s respectively. Thus, we also suggest that TAMMV of 125.75 cm/s should be investigated in additional studies as a cut-off point for stroke risk in HbSC individuals. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Uterine blood flow in sheep and goats during the peri-parturient period assessed by transrectal Doppler sonography

The aim of the present study was to evaluate uterine blood flow (UBF) during the postpartum period in small ruminants. The study involved measures of UBF in 5 ewes and 5 goats during the first 4 weeks after parturition. Transrectal quantification of UBF was assessed by determining the diameter (DM), time averaged mean velocity (TAMEAN), blood flow volume (BFV), blood flow acceleration (ACCE) and pulsatility index (PI) in the uterine arteries ipsilateral to the previously gravid uterine horn(s) at Wk 20 of gestation and every 3days from the day of parturition (D 0) until Day 27 postpartum (D 27). The diameters of the uterine arteries decreased (P<0.01) in both species during the postpartum period. The results revealed decreases (P<0.0001) in BFV, ACCE and TAMEAN, while PI increased during the postpartum period in both sheep and goats. Furthermore, there were positive correlations (P<0.05) between blood flow parameters in sheep and goats, respectively (BFV and DM, r=0.62 and 0.58; BFV and ACCE, r=0.32 and 0.26; BFV and TAMEAN, r=0.51 and 0.37). There were negative correlations (P<0.05) between PI and other parameters (PI and BFV, r=−0.39 and −0.36; PI and DM, r=−0.54 and −0.24; PI and ACCE, r=−0.58 and −0.48; and PI and TAMEAN, r=−0.80 and −0.79) in sheep and goats, respectively. Altogether, these results indicate that non-invasive Doppler ultrasound parameters provide important information toward understanding changes in the vasculature and its perfusion of the uterus during the postpartum period in sheep and goats.

EXpanding Treatment for Existing Neurological Disease (EXTEND): An Open-Label Phase II Clinical Trial of Hydroxyurea Treatment in Sickle Cell Anemia.

BackgroundCerebral vasculopathy in sickle cell anemia (SCA) begins in childhood and features intracranial arterial stenosis with high risk of ischemic stroke. Stroke risk can be reduced by transcranial doppler (TCD) screening and chronic transfusion therapy; however, this approach is impractical in many developing countries. Accumulating evidence supports the use of hydroxyurea for the prevention and treatment of cerebrovascular disease in children with SCA. Recently we reported that hydroxyurea significantly reduced the conversion from conditional TCD velocities to abnormal velocities; whether hydroxyurea can be used for children with newly diagnosed severe cerebrovascular disease in place of starting transfusion therapy remains unknown.ObjectiveThe primary objective of the EXpanding Treatment for Existing Neurological Disease (EXTEND) trial is to investigate the effect of open label hydroxyurea on the maximum time-averaged mean velocity (TAMV) after 18 months of treatment compared to the pre-treatment value. Secondary objectives include the effects of hydroxyurea on serial TCD velocities, the incidence of neurological and non-neurological events, quality of life (QOL), body composition and metabolism, toxicity and treatment response, changes to brain magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA), genetic and serologic markers of disease severity, and cognitive and pulmonary function.MethodsThis prospective Phase II trial will enroll children with SCA in Jamaica, between the ages of 2 and 17 years, with either conditional (170-199 cm/sec) or abnormal (≥ 200 cm/sec) TCD velocities. Oral hydroxyurea will be administered daily and escalated to the maximum tolerated dose (MTD). Participants will be seen in the Sickle Cell Unit (SCU) in Kingston, Jamaica monthly until achieving MTD, and then every 3 months. TCD will be performed every 6 months.ResultsCurrently, 43 participants have been enrolled out of a projected 50. There was one withdrawal due to immigration, with no permanent screen failures. Of the 43 enrolled, 37 participants have initiated study treatment.ConclusionsThis trial investigates the effects of hydroxyurea treatment at MTD in children with conditional or abnormal TCD velocities before transfusion therapy and may represent an important advance towards establishing a suitable non-transfusion protocol for stroke prevention in children with SCA. The trial outcomes will have profound significance in developing countries where the disease burden is highest.ClinicalTrialClinicalTrials.gov NCT02556099; https://clinicaltrials.gov/ct2/show/NCT02556099 (Archived by WebCite at http://www.webcitation.org/6k1yMAa9G)

The effects of sildenafil citrate on feto-placental development and haemodynamics in a rabbit model of intrauterine growth restriction.

The present study evaluated the effectiveness of sildenafil citrate (SC) to improve placental and fetal growth in a diet-induced rabbit model of intrauterine growth restriction (IUGR). Pregnant rabbits were fed either ad libitum (Group C) or restricted to 50% of dietary requirements (Group R) or restricted and treated with SC (Group SC). The treatment with SC improved placental development by increasing vascularity and vessel hypertrophy in the decidua. The assessment of feto-placental haemodynamics showed higher resistance and pulsatility indices at the middle cerebral artery (MCA) in fetuses treated with SC when compared with Group R, which had increased systolic peak and time-averaged mean velocities at the MCA. Furthermore, fetuses in the SC group had significantly higher biparietal and thoracic diameters and longer crown-rump lengths than fetuses in Group R. Hence, the SC group had a reduced IUGR rate and a higher kit size at birth compared with Group R. In conclusion, SC may provide potential benefits in pregnancies with placental insufficiency and IUGR, partially counteracting the negative effects of food restriction on placental development and fetal growth. However, the present study also found evidence of a possible blood overflow in the brain that warrants further investigation.

Near wake study of counter-rotating horizontal axis tidal turbines based on PIV measurements in a wind tunnel

The reveal of the near wake structure and development is of vital importance to the understanding of the working principle and power coefficient of tidal turbines. In this paper, the detailed near wake flow field was visualized by high resolution particle image velocimetry (PIV) technique, and the time-averaged mean velocity (both axial and tangential) and phase-locked transient velocity were measured, respectively, for a counter-rotating horizontal axis tidal turbine in the wind tunnel. The vortex was captured by vorticity and swirling strength calculation of the vector field for each phase, and the vortex formation and development were analyzed based on the summation of the data from all the different phases. To achieve more information about vortex, the experiment was conducted for two different axis distances and three different tip speed ratios. The existence of the rear rotor affects the trajectory of vortices shed from the front rotor and enhances the velocity deficit of the free stream. The experimental result can serve as a reference for numerical simulations.

Long-term treatment follow-up of children with sickle cell disease monitored with abnormal transcranial Doppler velocities

AbstractStroke risk in sickle cell anemia (SCA), predicted by high transcranial Doppler (TCD) velocities, is prevented by transfusions. We present the long-term follow-up of SCA children from the Créteil newborn cohort (1992-2012) detected at risk by TCD and placed on chronic transfusions. Patients with normalized velocities and no stenosis were treated with hydroxyurea, known to decrease anemia and hemolytic rate. Trimestrial Doppler was performed and transfusions restarted immediately in the case of reversion to abnormal velocities. Patients with a genoidentical donor underwent transplant. Abnormal time-averaged maximum mean velocities (TAMMV) ≥200 cm/s were detected in 92 SCA children at a mean age of 3.7 years (range, 1.3-8.3 years). No stroke occurred posttransfusion after a mean follow-up of 6.1 years. Normalization of velocities (TAMMV < 170 cm/s) was observed in 83.5% of patients. Stenosis, present in 27.5% of patients, was associated with the risk of non-normalization (P < .001). Switch from transfusions to hydroxyurea was prescribed for 45 patients, with a mean follow-up of 3.4 years. Reversion, predicted by baseline reticulocyte count ≥400 × 109/L (P < .001), occurred in 28.9% (13/45) patients at the mean age of 7.1 years (range, 4.3-9.5 years). Transplant, performed in 24 patients, allowed transfusions to be safely stopped in all patients and velocities to be normalized in 4 patients who still had abnormal velocities on transfusions. This long-term cohort study shows that transfusions can be stopped not only in transplanted patients but also in a subset of patients switched to hydroxyurea, provided trimestrial Doppler follow-up and immediate restart of transfusions in the case of reversion.

Original Research: Sickle cell anemia and pediatric strokes: Computational fluid dynamics analysis in the middle cerebral artery.

Children with sickle cell anemia (SCA) have a high incidence of strokes, and transcranial Doppler (TCD) identifies at-risk patients by measuring blood velocities in large intracerebral arteries; time-averaged mean velocities greater than 200 cm/s confer high stroke risk and warrant therapeutic intervention with blood transfusions. Our objective was to use computational fluid dynamics to alter fluid and artery wall properties, to simulate scenarios causative of significantly elevated arterial blood velocities. Two-dimensional simulations were created and increasing percent stenoses were created in silico, with their locations varied among middle cerebral artery (MCA), internal carotid artery (ICA), and anterior cerebral artery (ACA). Stenoses placed in the MCA, ICA, or ACA generated local increases in velocity, but not sufficient to reach magnitudes > 200 cm/s, even up to 75% stenosis. Three-dimensional reconstructions of the MCA, ICA, and ACA from children with SCA were generated from magnetic resonance angiograms. Using finite element method, blood flow was simulated with realistic velocity waveforms to the ICA inlet. Three-dimensional reconstructions revealed an uneven, internal arterial wall surface in children with SCA and higher mean velocities in the MCA up to 145 cm/s compared to non-SCA reconstructions. There were also greater areas of flow recirculation and larger regions of low wall shear stress. Taken together, these bumps on the internal wall of the cerebral arteries could create local flow disturbances that, in aggregate, could elevate blood velocities in SCA. Identifying cellular causes of these microstructures as adhered blood cells or luminal narrowing due to endothelial hyperplasia induced by disturbed flow would provide new targets to treat children with SCA. The preliminary qualitative results provided here point out the critical role of 3D reconstruction of patient-specific vascular geometries and provide qualitative insight to complex interplay between vascular geometry and rheological properties possibly altered by SCA.