Time-averaged Maximum Velocity Research Articles

P118: THE ROLE OF HEMOGLOBIN AND HEMOLYSIS ON TRANSCRANIAL DOPPLER VELOCITIES IN CHILDREN WITH SICKLE CELL DISEASE: DATA FROM A NATURAL HISTORY COHORT

Background: Children with sickle cell disease (SCD) are at increased risk of cerebrovascular events that can impact neurocognitive development and quality of life (Colombatti 2016). Transcranial Doppler ultrasound (TCD) is a validated screening tool to identify pediatric SCD patients with the highest risk of stroke, to start on a preventive chronic blood transfusion regimen (Estcourt 2020; Inusa 2019). We aimed to evaluate the distribution of TCD velocities in a pediatric natural history cohort and investigate their correlation with hematological variables and treatments. Methods: We performed a retrospective analysis on data from a prospective pediatric cohort followed from January 1, 2009, to December 31, 2020 (censoring date). We used transcranial Doppler imaging (TCDi) and classified results according to STOP criteria, considering terminal internal carotid artery (TICA) and middle cerebral artery (MCA) time-averaged maximum mean velocities (TAMMVs). Hematological, clinical, and treatment variables were available from the natural history cohort database. Two-sample and Welch t-tests for unequal variances were used to compare mean hemoglobin (Hb) values and hemolysis markers in patients with and without abnormal/conditional TCDi results. Fisher and chi-square tests were used to compare categorical variables. Linear regression models were used to assess the effects of MCA and TICA TAMMVs as continuous variables on Hb. Odds ratios (ORs) for neurological events at different Hb levels were estimated using generalized estimated equations (GEE) with a binomial distribution, logistic function, and exchangeable correlation structure, allowing for correlation among repeated observations for the same patient. Multivariable GEE including characteristics and treatment variables were used to evaluate the association between neurological events and Hb. Results: Of the 182 SCD patients in the cohort, 169 had assessments of cerebral vasculopathy, and 155 had evaluable TCDi (583 exams). The median follow-up of the entire cohort was 79.8 months (range: 2.1–298.6 months) (interquartile range [IQR]: 36.9–126.3 months). The median age at the censoring date was 13.4 years (IQR: 9.1–17.5 years). Patients with abnormal/conditional TCDi results had lower Hb (8.4 vs 8.9 g/dL, P≤0.0001) and higher reticulocyte counts (317,766 vs 262,750/mm3, P≤0.0001), lactate dehydrogenase (843 vs 690 U/L, P=0.0012), and aspartate aminotransferase (61 vs 54 U/L, P=0.0007) compared with patients with normal/low results. We detected an inverse linear correlation between TICA/MCA TAMMVs and Hb (Figure 1A and 1B). Univariate analysis showed significant inverse correlation between abnormal/conditional TCDi results and Hb considered as a continuous variable (OR: 0.484, P<0.001). In the multivariate analysis, the correlation between TCDi results and Hb remained significant; moreover, the risk of presenting abnormal/conditional TCDi results decreased with age (OR: 0.833, P<0.0064). Conclusions: This analysis from our natural history cohort shows a significant inverse correlation between Hb and MCA and TICA velocities, supporting the beneficial effect of higher Hb levels in reducing TAMMV.

Chios ram testicular blood flow and echotexture changes depending on age, season and ejaculation process.

The present study aimed to investigate the impact of age, season and ejaculation on ram testicular blood flow and echotexture. The survey was conducted biweekly on 7 Chios rams for one year, including breeding and non-breeding periods. The rams were divided into 2 age groups: 3 rams 2-6 years old (mature) and 4 rams 9-13 years old (old). Hemodynamic indices [Pulsatility index (PI), Resistive index (RI), End-diastolic velocity (EDV), testicular artery Diameter (D), Time-averaged maximum velocity (TAVM), Blood flow volume (BFV)] and echotexture parameters [Mean value (MV), Contrast (Con), Gray value distribution (GVD), Run length distribution (RunLD), Long run emphasis (LRunEm), Entropy (Ent), Correlation (Cor), Standard deviation (StD), Gray variance (GV) and Gradient mean value (GMV)] were evaluated in each testis before and after ejaculation. Ejaculation did not affect testes blood flow or echotexture (p>0.05). PI and RI were higher in the breeding period compared to the non-breeding period, for both testes (p⟨0.001). Left testis GV and Cor before ejaculation were lower (p=0.01) and higher (p=0.03), respectively, in the breeding compared to the non-breeding period. Left testis D (p=0.005) and BFV (p⟨0.001) were higher in old compared to mature rams after ejaculation. Right testis Con (p=0.03) and Cor (p=0.05) before ejaculation were higher in old rams, whereas right testis Ent after ejaculation was higher in mature rams (p=0.05). In conclusion, testicular blood flow and echotexture are affected by season and ram age, but not by ejaculation.

The Role of Hemoglobin and Hemolysis on Transcranial Doppler Velocities in Children with Sickle Cell Disease: Data from a Natural History Cohort

Background: Children with sickle cell disease (SCD) are at increased risk of cerebrovascular events that can impact neurocognitive development and quality of life (Colombatti 2016). Transcranial Doppler ultrasound (TCD) is a validated screening tool to identify pediatric SCD patients with the highest risk of stroke to start on a preventive chronic blood transfusion regimen (Estcourt 2020; Inusa 2019). High TCD velocities are an indication to start disease-modifying treatments or consider disease-curative options in children with SCD (Khemani 2019). However, real-world pediatric data on the correlation between hematological variables and TCD results are scarce (Salama 2020). We aimed to evaluate the distribution of TCD velocities in a pediatric natural history cohort and investigate their correlation with hematological variables and treatments.Methods: We performed a retrospective analysis on data from a prospective pediatric cohort followed from January 1,2009, to December 31, 2020 (censoring date). Standard care includes annual TCD from 2 years of age. We used transcranial Doppler imaging (TCDi) and classified results according to STOP criteria, considering terminal internal carotid artery (TICA) and middle cerebral artery (MCA) time-averaged maximum mean velocities (TAMMVs). Only complete exams with right and left measures available for both vessels were included. Hematological, clinical, and treatment variables were available from the natural history cohort database. Patients were divided according to genotype: HbSS/HbSβ 0 or HbSC/HbSβ +.Two-sample and Welch t-tests for unequal variances were used to compare mean hemoglobin (Hb) values and hemolysis markers in patients with and without abnormal/conditional TCDi results. Fisher and chi-square tests were used to compare categorical variables. Linear regression models were used to assess the effects of MCA and TICA TAMMVs as continuous variables on Hb. Odds ratios (ORs) for neurological events at different Hb levels were estimated using generalized estimated equations (GEE) with a binomial distribution, logistic function, and exchangeable correlation structure, allowing for correlation among repeated observations for the same patient. Multivariable GEE including characteristics and treatment variables were used to evaluate the association between neurological events and Hb.Results: Of the 182 SCD patients in the cohort, 169 had assessments of cerebral vasculopathy, and 155 had evaluable TCDi (583 exams). The median follow-up of the entire cohort was 79.8 months (range: 2.1-298.6 months) (interquartile range [IQR]: 36.9-126.3 months). The median age at the censoring date was 13.4 years (IQR: 9.1-17.5 years); 130 were HbSS/HbSβ 0, and 25 were HbSC/HbSβ +. Basic demographic characteristics of the cohort are in Table 1. The distribution of TCDi results was significantly different between genotypes (P<0.0001): in the HbSC/HbSβ + group (70 exams), 14 were normal (20.0%), and 56 were low (80.0%); in the HbSS/HbSβ 0 group (513 exams), 8 were abnormal (1.6%), 56 were conditional (10.9%), 311 were normal (60.6%), and 138 were low (26.9%). Only 37/138 (26.8%) low TCDi results were confirmed as stenosis at the nearest MRA. Patients with abnormal/conditional TCDi results had lower Hb (8.4 vs 8.9 g/dL, P≤0.0001) and higher reticulocyte counts (317,766 vs 262,750/mm 3, P≤0.0001), lactate dehydrogenase (843 vs 690 U/L, P=0.0012), and aspartate aminotransferase (61 vs 54 U/L, P=0.0007) compared with patients with normal/low results.We detected a linear correlation between TICA/MCA TAMMVs and Hb (Figure 1A and 1B). Univariate analysis showed significant inverse correlation between abnormal/conditional TCDi results and Hb considered as a continuous variable (OR: 0.484, P<0.001). In the multivariate analysis, the correlation between TCDi results and Hb remained significant; moreover, the risk of presenting abnormal/conditional TCDi results decreased with age (OR: 0.833, P<0.0064).Conclusions: This analysis from our natural history cohort shows a significant inverse correlation between Hb and MCA and TICA velocities, supporting the beneficial effect of higher Hb levels in reducing TAMMV. Disease-modifying therapies increasing Hb and reducing hemolysis could be helpful in reducing TAMMV in children with SCD.Funding: This study was supported by Global Blood Therapeutics. [Display omitted] DisclosuresAgodoa: Global Blood Therapeutics: Current Employment, Current equity holder in publicly-traded company. Beaubrun: Global Blood Therapeutics: Current Employment, Current equity holder in publicly-traded company. Biffi: BlueBirdBio: Consultancy, Other: Advisory Board. Colombatti: Global Blood Therapeutics: Research Funding; Addmedica: Consultancy; Forma Therapeutics: Consultancy; Novartis: Consultancy; NovoNordisk: Consultancy; BlueBirdBio: Consultancy; Global Blood Therapeutics: Consultancy; BlueBirdBio: Research Funding.

Evaluation of Functional Structures in the Ovaries Pre and Post Ovulation by Doppler Ultrasonography in Bitches

In this article, functional structures on the ovaries of bitches before and after ovulation are evaluated with Doppler ultrasonography and information concerning the interpretations of findings are transferred. Doppler effect is the first step of Doppler imaging. This effect is the shift in the frequency of the transmitted ultrasound. Spectral and/or color Doppler ultrasonography is the easiest and the most important diagnostic technique in assessing ovarian hemodynamic. The Doppler shift and the Doppler angle are used by the instrument for computing blood velocity. Spectral Doppler contains quantitative information. This information includes the peak systolic volume, end-diastolic volume, and time-averaged maximum velocities, Doppler indices (pulsatility index; PI; resistance index, RI). Doppler indices are used to assess vascular perfusion and computed using values PSV, EDV, and TAMV. The presence of blood flow in a color doppler image is shown as color-encoded and superimposed on a real-time B-mode image. Color Doppler imaging provides detailed monitoring of the local blood flow in ovarian follicles and corpus luteum. The discovery of Doppler ultrasonography that includes blood flow information has led to the formation of research issues in veterinary medicine. It is a developing technology in veterinary medicine. This technology is provided an understanding of hemodynamics and the relationship between blood flow and physiological-pathophysiological processes.

Experimental measurements of airflow features and velocity distribution exhaled from sneeze and speech using particle image velocimetry

Airflow exhaled from sneeze and speech is an important source of viruses and droplets in daily life and may cause imperceptible virus propagation. The velocities of sneeze and speech airflow exhaled from 10 healthy young participants repeatedly using high-frequency (2986 Hz) particle image velocimetry are measured. The parameters for describing the dynamic process of sneeze airflow, such as sneeze duration time (SDT), peak velocity time (PVT), maximum velocities, and sneeze spread angle, are analyzed. The sneeze airflow lasts 430 ms (SDT) and reaches the peak velocity in the first 20 ms (PVT). The maximum sneeze airflow velocity is approximately 15.9 m/s. The temporal variation of the sneeze velocity exhibits the gamma distribution. For speech airflow, the maximum instantaneous velocity and maximum time-averaged velocity are reported. The maximum instantaneous velocity is approximately 6.25 m/s, whereas the time-averaged value is only 0.208 m/s owing to the extremely small airflow velocity among syllables. The vertical/horizontal spread angles of the airflow are 15.1°/15.4° for sneeze and 52.9°/42.9° for speech. The difference in airflow features based on gender is generally slight for both sneeze and speech. Subsequently, an ensemble-average operation is conducted to obtain the general and representative velocity distributions. We report each component of the temporal and spatial velocity distributions of the sneeze airflow and the time-averaged velocity distribution of the speech airflow. These detailed distribution data can provide a comprehensive understanding of sneeze and speech airflow movement mechanisms as well as a detailed database for future sneeze and speech computational fluid dynamics simulations.

Fetal Superior Vena Cava Blood Flow and Its Fraction of Cardiac Output: A Longitudinal Ultrasound Study in the Second Half of Pregnancy.

Introduction: In the fetus, a large proportion of the superior vena cava blood flow (QSVC) comes from the brain. To provide the possibility of using this blood flow as a representation of fetal brain circulation, we aimed to determine the fetal QSVC and its fraction of cardiac output during the second half of physiological pregnancies.Materials and Methods: This was a prospective longitudinal study specifically designed for studying fetal hemodynamic development. Healthy women with singleton low-risk pregnancies were included. Ultrasonography was performed at 4-weekly intervals from 20+0 gestational weeks to term. Doppler velocity recordings of the superior vena cava (SVC) and cardiac ventricular outflow tracts were used to obtain the time-averaged maximum velocities (TAMxV). Vessel diameters were measured to calculate their cross-sectional areas (CSA): π(diameter/2)2. Blood flow (Q) was computed as: h*TAMxV*CSA, h being the spatial blood velocity profile, to obtain QSVC and cardiac outputs. The sum of left and right ventricular cardiac outputs constituted the combined cardiac output (CCO). Ultrasound biometry based estimated fetal weight and brain weight were used to normalize the flow. QSVC was also expressed as the fraction (%) of CCO. Gestational age specific percentiles were established for each blood flow parameter using multilevel modeling.Results: Totally, 134 of the 142 included women were eligible for the study with 575 sets of observations. The SVC mean diameter (19–52 mm), mean TAMxV (8.83–16.14 cm/s), and QSVC (15.4–192.0 ml/min) increased significantly during the second half of pregnancy (p < 0.001) while the mean QSVC normalized by estimated fetal weight (49 ml/min/kg) and by estimated brain weight (50 ml/min/100 g) were relatively stable. Similarly, the mean CCO increased (156–1,776 ml/min; p < 0.001) while the normalized CCO (509 ± 13 ml/min/kg) and QSVC as a fraction of CCO (10 ± 0.92%) did not change significantly with gestational age.Conclusion: We provide reference values for fetal QSVC which increases significantly with gestation, and constitutes roughly 10% of the fetal CCO at any time during the second half of pregnancy.

Analyzing the correlation between uterine involution and blood flow in post-partum dairy cows

The objective of this study was to assess the applicability of trans-rectal color Doppler ultrasonography for quantification of uterine blood flow in 30 healthy lactating Jersey cows on a weekly interval from days 0 to 56 after parturition (day 0). Significantly higher time average mean velocity (TAMEAN), time average maximum velocity (TAMAX) and blood flow volume (BFV-TAMEAN and BFV-TAMAX) in artery ipsilateral to previous gravid uterine horn (PGUH) was found as compared to contralateral middle uterine artery (MUA) on day 0 to 14 postpartum. Similarly, transverse diameter (D) of ipsilateral MUA was significantly higher as compared to contralateral MUA during first two weeks after parturition. Clinical uterine involution completed on day 32.47±0.85 postpartum as demonstrated by B-mode ultrasonography and a significant correlation (r= 0.31–0.44 from day 7–28) between size of PGUH and BFV-TAMAX was found. Also, significant correlation between transverse diameter of ipsilateral (r=0.56–0.80) and contralateral (r=0.51–0.79) MUA-D and BFV-TAMAX was found on different examination days. In conclusion, trans-rectal Doppler ultrasonography was a useful tool to investigate haemodynamic changes whereas PI, RI, Doppler pulse duration and systolic upstroke time were found unsuitable to indagate alterations in uterine perfusion during post-partum period.

Does radial or median nerve blocks affect the area and blood flow of radial artery?

Background and aimsRadial artery is a common site of cannulation in acute care setting. There are conflicting reports as to which nerve, radial or median or both supplies the radial artery. We did this prospective study in patients undergoing minor procedures under peripheral nerve blocks to ascertain which nerve block, radial or median increases the cross sectional area and blood flow in the radial artery. MethodsNinety ASA I/II patients undergoing upper limb minor surgeries under various blocks (radial or median or radial + median nerve) were enrolled in this study. Patients in group R were those who received Ultrasound-guided (USG) radial nerve block, group M median nerve block while group MR received both the nerve blocks. The primary objective was to assess the increase in cross sectional area (CSA) of radial artery in the groups after the block. Secondary objectives included assessment of time average maximum velocity (TAMAX) and blood volume (BV) after the block. ResultsThe CSA, TAMAX and BV of radial artery increased in all the three groups. Within each group the difference between the preblock and postblock parameters were highly significant. However, the differences are greater in groups M and M + R than in group R; (P < 0.001). ConclusionUltrasound-guided median nerve block causes arterial vasodilation, and an increase in radial artery blood flow velocity. There was no added benefit of radial block along with median block in increasing the blood flow further.

Post-exercise pulsatility index indicates treatment effects in peripheral arterial occlusive disease (PAOD).

BackgroundHypothesis: Post-exercise measurements better discriminate PAOD-patients from healthy persons and they more sensitively detect hemodynamic improvements after treatment procedures than resting measurements.MethodsA total of 19 healthy volunteers and 23 consecutive PAOD-patients underwent measurements of peak systolic velocity (PSV), end-diastolic velocity (EDV), minimal diastolic velocity (MDV), time-averaged maximum velocities (TAMAX), resistance index (RI) and pulsatility index (PI) before and after a standard exercise test (at 1, 2, 3, 4 and 5 min) before and after treatment (incl. epidemiological data, PAOD risk factors and comorbidities).ResultsIn resting values, healthy persons and PAOD-patients did not differ significantly in any of the hemodynamic parameters. PSV increased after treatment in PAOD-patients by 5 cm/s (paired t‑test, p: 0.025); however, when the amplitude of autoregulatory changes related to the resting values were calculated, PAOD-patients showed clearly less hemodynamic changes after exercise than healthy persons (p: 0.04; 0.002; <0.001 for PSV, TAMAX and PI, resp.). The time course after exercise was compared by repeated measures of ANOVA. Healthy persons differed significantly in PI, RI and PSV from PAOD patients before and after treatment (p<0.001 each). The PAOD-patients revealed a significantly improved PI after treatment (p: 0.042). The only factor contributing significantly to PI independently from grouping was direct arterial vascularization as compared to discontinuous effects by an obstructed arterial tree.ConclusionHealthy persons cannot be well differentiated from PAOD-patients solely by hemodynamics at rest but by characteristic changes after standard exercise. Treatment effects are reflected by higher PI-values after exercise.

Fetal Umbilical Vein Flow in the Classification of Fetuses with Growth Restriction

Objectives: To assess umbilical vein (UV) blood flow in fetal growth restriction (FGR) and in pregnancy with small for gestational age (SGA) fetus. To evaluate the predictive capacity of UV blood flow (QUV) in the discrimination of SGA fetuses from FGR before and after 32 weeks of pregnancy. Methods: Sixty-five women with a recent diagnosis of FGR or SGA fetuses were enrolled and underwent a complete fetal Doppler examination comprehending QUV. We collected SGA (n = 34), early-FGR (n = 9), and late-FGR (n = 22) fetuses. Results: UV diameter was lower in early and late-FGR compared to SGA, while time-averaged maximum velocity (TAMXV) was lower only in early-FGR. UV blood flow (QUV) and QUV corrected for estimated fetal weight (cQUV) were significantly lower in early-FGR and late-FGR compared to SGA. The receiver operating characteristic (ROC) curves analysis of cQUV showed a significant predictive capacity for SGA diagnosis before and after 32 weeks. Conclusions: The evaluation of UV blood flow allows distinguishing SGA fetuses from FGR. The assessment of UV flow should be taken into consideration in future research of new parameters to differentiate SGA from FGR.

Reference ranges of fetal superior vena cava blood flow velocities and pulsatility index in the second half of pregnancy: a longitudinal study

BackgroundFetal superior vena cava (SVC) is essentially the single vessel returning blood from the upper body to the heart. With approximately 80-85% of SVC blood flow representing cerebral venous return, its interrogation may provide clinically relevant information about fetal brain circulation. However, normal reference values for fetal SVC Doppler velocities and pulsatility index are lacking. Our aim was to establish longitudinal reference intervals for blood flow velocities and pulsatility index of the SVC during the second half of pregnancy.MethodsThis was a prospective study of low-risk singleton pregnancies. Serial Doppler examinations were performed approximately every 4 weeks to obtain fetal SVC blood velocity waveforms during 20–41 weeks. Peak systolic (S) velocity, diastolic (D) velocity, time-averaged maximum velocity (TAMxV), time-averaged intensity-weighted mean velocity (TAMeanV), and end-diastolic velocity during atrial contraction (A-velocity) were measured. Pulsatility index for vein (PIV) was calculated.ResultsSVC blood flow velocities were successfully recorded in the 134 fetuses yielding 510 sets of observations. The velocities increased significantly with advancing gestation: mean S-velocity increased from 24.0 to 39.8 cm/s, D-velocity from 13.0 to 19.0 cm/s, and A-velocity from 4.8 to 7.1 cm/s. Mean TAMxV increased from 12.7 to 23.1 cm/s, and TAMeanV from 6.9 to 11.2 cm/s. The PIV remained stable at 1.5 throughout the second half of pregnancy.ConclusionsLongitudinal reference intervals of SVC blood flow velocities and PIV were established for the second half of pregnancy. The SVC velocities increased with advancing gestation, while the PIV remained stable from 20 weeks to term.

The role of umbilical artery velocities in the clinical assessment of twin-twin transfusion syndrome at stage.

To analyze the discordances of the umbilical artery velocities between pregnancies with twin-twin transfusion syndrome (TTTS) at stage I and those with normal monochorionic-diamniotic (MCDA) twins, and investigate the value of their discordances in predicting TTTS at stage I. We recruited 58 twin pregnancies with TTTS at stage I and 60 normal MCDA twin pregnancies in a tertiary referral center retrospectively. The umbilical artery velocities and their discordances were compared between the normal and TTTS twins. The discordances of umbilical artery mean diastolic velocity (UA-MDV), umbilical artery time-averaged maximum velocity (UA-TAmax), umbilical artery peak systolic velocity (UA-PSV), and umbilical artery end-diastolic velocity (UA-EDV) were higher in the TTTS group than in the normal group. In TTTS co-twins, the UA-MDV, UA-TAmax, UA-PSV, and UA-EDV in recipients were higher than those in donors. The discordances of UA-TAmax and UA-PSV were found to be independent predicting factors for TTTS at stage I. Co-twin umbilical artery velocity discordances were significantly associated with stage I TTTS. The results suggest that UA-TAmax and UA-PSV might be new parameters for predicting TTTS at stage I.

530 Uterine artery volumes, small for gestational age, preeclampsia, and adverse neonatal outcomes

To determine if uterine artery flow volume (UtaV) estimated throughout gestation is different in pregnancies complicated by SGA, pre-eclampsia (PE), or adverse neonatal outcomes; to evaluate the potential of using UtaV as a screening tool when combined with maternal characteristics. This prospective longitudinal study over a 5-year period measured uterine artery vessel diameter and time-averaged maximum velocity (TAMXV) using color Doppler between 11+0 to 14+0, 18+0 to 22+6, and 28+0 to 34+6 weeks of gestation. UtaV was calculated from the vessel diameter and TAMXV. SGA was defined as birthweight < 10th percentile. PE was defined using ACOG criteria. A composite adverse neonatal outcome (ANO) was defined including presence of any of the following: 5 min Apgar score <5, arterial pH <7.10, respiratory distress syndrome, grade III or IVH (III or IV), seizures or neonatal death. Student t-tests were used to compared UtaV between normal and complicated pregnancies. ROC curves were constructed and AUCs compared. 397 pregnancies were included. Among pregnancies evaluated, SGA was seen in 26 (6.5%), PE in 22 (5.7%) and ANO in 22 (3.5%). The UtaV increased with gestational age (Figure). UtaV was significantly lower in SGA neonates in all trimesters but not in ANO (Table). UtaV was only significantly different in PE in the third-trimester. This difference persisted when UtaV was corrected for estimated fetal weight at the time of estimation (p=0.02). Prediction models for SGA including maternal characteristics: race, body mass index, smoking, hypertension, pre-gestational diabetes and UtaV had areas under the ROC curves of 0.68, 0.69 and 0.71 in first, second, and third trimesters, respectively. For PE, the AUC was 0.83, 0.82, 0.81, respectively. Uterine artery blood flow in all trimesters is reduced in pregnancies resulting in SGA. In pregnancies resulting in PE, UtaV was reduced in the third trimester. When combined with maternal characteristics, UtaV represents a promising screening marker for SGA and PE.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

232 Longitudinal assessment of umbilical vein flow, small for gestational age (SGA) and adverse neonatal outcomes

To determine if umbilical vein flow (QuV) estimated throughout gestation is different in pregnancies resulting in SGA or adverse neonatal outcomes and evaluate the potential of using this as a screening tool when combined with maternal characteristics. This prospective longitudinal study over a 5-year period measured umbilical vein diameter and time-averaged maximum velocity (TAMXV)using Color Doppler between 11 to 13 + 6, 18 to 21 + 6 and 28 to 34 weeks of gestation. QuV was calculated from the vein diameter and TAMXV. SGA was defined as birthweight < 10th percentile. QuV was not adjusted for estimated fetal weight as the later is in the causal pathway leading to SGA. A composite adverse neonatal outcome (ANO) was defined including presence of any of the following: 5 min Apgar score <5, arterial pH <7.10, respiratory distress syndrome, grade III or IVH (III or IV), seizures or neonatal death. Student t-tests were used to compared QuV between normal and complicated pregnancies. ROC curves were constructed and AUCs compared. Among 537 pregnancies evaluated, SGA was seen in 38 (7.1%) and ANO in 22 (4.1%).The QuV increased with gestational age (Figure). QuV and QuV adjusted for EFW were significantly lower in SGA and ANO groups in the second trimester. In the third-trimester, absolute QuV was significantly different only in pregnancies complicated by SGA. Prediction models for SGA including maternal characteristics: race, body mass index, smoking, hypertension, pre-gestational diabetes and QuV had areas under the ROC curves of, 0.69, 0.71 and 0.72 in first, second and third, trimesters respectively. Umbilical vein blood flow is reduced in pregnancies resulting in SGA and adverse neonatal outcomes and represents a promising screening marker when combined with maternal characteristics.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Intrauterine infusion of killed semen adversely affects uterine blood flow and endometrial gene expression of inflammatory cytokines in mares susceptible to persistent breeding-induced endometritis

Persistent breeding-induced endometritis (PBIE) is a leading cause of infertility in mares. The objective of the study was to assess genital perfusion and endometrial gene expression of inflammatory cytokines in mares classified as susceptible (n = 5) or resistant (n = 5) to PBIE. Ten mares were examined daily during estrus until 6 d after hCG-induced ovulation for two estrous cycles. Twenty-four hours after application of 1500 IU hCG, 4 mL of killed (by repeated freezing in liquid nitrogen and thawing at 50 °C) deep-frozen semen or sterile saline was instilled into the uterine body and examinations were carried out immediately before and 3, 6, and 12 h after intrauterine infusion. Examinations included blood sampling to determine plasma progesterone (P4) concentrations, and transrectal ultrasonography in B- and color Doppler mode to determine follicular and luteal size and blood flow, the extent of intrauterine fluid, as well as time-averaged maximum velocity (TAMV), blood flow volume (BFV), and blood flow resistance (expressed as pulsatility index, PI) of the uterine arteries. Additionally, endometrial biopsies were obtained at 24 h before, and 2 and 7 d after infusion, and mRNA expressions of IL1B, IL6, IL8, IL10, TNF, CASP3, and COX2 were determined by qRT-PCR. Statistical analyses were performed with mixed models. Intrauterine fluid retention (diameter >20 mm for at least 3 d) was found after infusion of killed semen in five susceptible mares. There was no treatment effect (semen vs saline; P > 0.05) on genital blood flow, plasma P4 concentration, and endometrial gene expression. In comparison to resistant mares, susceptible mares had an increased (P = 0.04) BFV of the uterine arteries at 24 h before intrauterine infusion of killed semen, and an increased (P = 0.03) PI at 2 d after infusion. The TAMV, plasma P4 concentrations, and follicular and luteal size and blood flow did not differ (P > 0.05) between resistant and susceptible mares. Endometrial mRNA expression of IL1B increased (P = 0.05) at 2 d after the infusion of killed semen in the susceptible mares, and the expression of IL10 increased (P = 0.003) at 7 d after the infusion within the resistant mares. Interleukin 6 mRNA was increased (P = 0.05) in susceptible compared to resistant mares at 2 d after infusion. In summary, an intrauterine infusion of killed semen increases uterine blood flow resistance and alters endometrial gene expression of inflammatory cytokines for at least 7 d but does not affect ovarian blood supply and luteal function in mares susceptible to PBIE.

Uterine, vaginal and placental blood flows increase with dynamic changes in serum metabolic parameters and oxidative stress across gestation in buffaloes.

The aims of the present study were to determine uterine, vaginal and placental blood flows by Doppler ultrasound cross-buffalo gestation and to evaluate the relationships among reproductive Doppler parameters and serum metabolic parameters as well as oxidative stress. Uterine (UA) and vaginal (VA) arteries were scanned every month, and placentome was scanned from month 4 till 8 in gestation. Time-averaged maximum velocity (TAMV), pulsatility index (PI), resistance index (RI), systolic/diastolic ratio (SD) and arterial diameter (AD) were used for accessing UA and VA hemodynamics. Time-averaged maximum velocity positively correlated with and AD, and both negatively correlated with their PI, RI and SD in UA and VA. TAMV and AD increased constantly in pregnancy, with maximum increase in months 4 and 9. Pulsatility index, RI and AD of UA decreased between months 4 and 9, while PI, RI and AD of VA decreased between months 5 and 9 and then increased in month 10 in pregnancy. Time-averaged maximum velocity of placentome blood flow increased exponentially from months 4 to 8, but decreased at the last two months in pregnancy. Serum lipids were significantly higher in the first month compared to all other months, while glucose was significantly lower in months 9 and 10. Malondialdehyde increased from month 3 till term, but peaked in month 5 and 10. Glutathione and catalase were highest in the first month and remained after. Time-averaged maximum velocity and AD for both UA and VA negatively correlated with serum lipids, glucose, catalase and glutathione, while positively correlated with malondialdehyde and total protein. Thus, increases in uterine blood flow (UtBF), vaginal blood flow (VaBF) and placental blood flow (PaBF) are associated with increased metabolism and oxidative stress in buffalo pregnancy.

Building Capacity and Assessing Stroke Risk with Transcranial Doppler Ultrasonography in Sub-Saharan Africa: The Reach Experience

Introduction: Transcranial Doppler (TCD) screening data from Uganda, Tanzania, and Nigeria have documented elevated velocities in &amp;gt;20% of children with sickle cell anemia (SCA) not receiving hydroxyurea treatment. Realizing Effectiveness Across Continents with Hydroxyurea (REACH, NCT01966731) has demonstrated the safety, feasibility, and benefits of hydroxyurea for children with SCA living in sub-Saharan Africa, especially when escalated to maximum tolerated dose (MTD). Whether hydroxyurea also confers protection against stroke risk in this setting remains unproven, though hydroxyurea-associated increases in hemoglobin and fetal hemoglobin, plus decreases in TCD arterial flow velocities, should lower the risk of both primary and secondary stroke. The availability of TCD equipment and appropriately trained and certified TCD examiners to perform this non-invasive and inexpensive procedure is an important limitation in low-resource settings. Methods: REACH teams in Angola, Democratic Republic of Congo, Kenya, and Uganda identified two local persons at each site to receive formal TCD training and certification from two experienced and certified super-users, one from Uganda and one from the US. Initial training included hands-on teaching at each site by the Ugandan trainer, followed by didactic teaching and hands-on examinations at a central African location with both trainers and all four REACH teams. Follow-up training included monthly web-based teaching sessions of TCD technique and discussion of centrally reviewed exams. Each local examiner had at least 30 completed examinations reviewed, critiqued, and discussed together with the trainers before becoming formally certified as a REACH TCD examiner. After certification, all REACH participants taking hydroxyurea at a stable dose were eligible for TCD using a standardized protocol with identical Sonara/tek advanced non-imaging TCD ultrasound units with 2MHz probes and version 7 software (Natus, Middleton, WI). Time-averaged maximum velocities (TAMV) were measured in the middle cerebral artery, distal internal carotid artery, and the bifurcation. The highest TAMV was recorded and categorized as normal (&amp;lt;170 cm/sec), conditional (170-199 cm/sec), or abnormal (≥200 cm/sec) and correlated with laboratory and clinical parameters. Results: Between November 2018 and March 2020, a total of 481 children in REACH received TCD screening; the average age was 9.3 ± 2.6 years, on hydroxyurea for 43 ± 8 months at an average dose of 23.5 ± 5.0 mg/kg/day with good response (Hb = 8.4 ± 1.3 g/dL, HbF = 23.9 ± 5.0%). There were 16 (3.3%) inadequate exams, defined as no vessel flow in either hemisphere; 5 inadequate exams were in children with prior stroke at hydroxyurea initiation and 1 with stroke on treatment. Of 465 adequate exams, the overall median TAMV was 128 cm/sec (IQR 25 cm/sec) with 449 normal velocities (96.6% overall, range by site 95.1-99.2%), 16 conditional velocities (3.4% overall, range by site 2.3-4.9%), and no abnormal velocities. In univariate analysis, maximum TAMV was inversely correlated with hemoglobin (r = -0.29, p&amp;lt;0.0001), age (r = -0.23, p&amp;lt;0.0001), and fetal hemoglobin (r = -0.12, p=0.027); and positively correlated with reticulocytes (r = 0.17, p&amp;lt;0.001). No gender difference was noted, but alpha thalassemia trait (2-gene deletion) was associated with significantly lower TCD velocities, while G6PD A- deficiency had no observed effects. Conclusions: Robust TCD screening capability was developed in REACH with detailed training, certification, and oversight of local personnel, most of whom had no prior experience. Compared to untreated children, very few REACH participants had elevated TAMV velocities, confirming that hydroxyurea lowers TCD velocities and reduces stroke risk for children with SCA in sub-Saharan Africa. The observed associations between TAMV and both hemoglobin and fetal hemoglobin document the importance of escalating hydroxyurea to achieve and maintain an optimized dose. In low-resource settings, TCD screening efforts by trained and certified examiners should be aligned with hydroxyurea treatment protocols that feature dose escalation, to provide a feasible and effective stroke prevention program. TCD screening of African children with SCA will allow early identification of stroke risk and optimized hydroxyurea dosing, thereby reducing morbidity and mortality in this vulnerable population. Disclosures Aygun: National Heart, Lung, and Blood Institute: Research Funding; bluebird bio: Membership on an entity's Board of Directors or advisory committees, Research Funding; Patient-Centered Outsomes Research Institute: Research Funding; National Institute of Nursing Research: Research Funding.

Evaluation of haemodynamic changes of uterine arteries using Doppler ultrasonography during different stages of pregnancy in Bos indicus cows

The objectives of the study were to evaluate haemodynamic changes and their relationships among ipsilateral (IPS) and contralateral (CONT) uterine arteries (UA) during different stages of pregnancy in Bos indicus cows. Multiparous pregnant cows (n=40) having a gestation length 30.47±0.54 (mean±SD) days were randomly enrolled and subjected to Doppler ultrasonography sequentially at 1st, 2nd, 4th, 6th and 8th months of gestation. Blood flow indices including diameter of UA (mm), blood flow volume (BFVo, ml/min), blood flow velocity (BFVe, cm/s), time-averaged maximum velocity (TAMV, cm/s), pulsatility index (PI) and resistance index (RI) were recorded. Data were analysed with mixed models using the PROC MIXED procedures, and Pearson correlation coefficients were calculated using the PROC CORR statement in SAS. The final statistical models included the fixed effects of side of UA, gestation month and the interaction between side of UA and gestation month. Results revealed that the mean diameter of the UA (12.13±0.22 vs. 10.09±0.22), BFVo (1236.33±0.55 vs. 770.41±0.55), BFVe (17.18±0.42 vs. 15.58±0.42) and TAMV (17.11±0.44 vs. 15.77±0.44) was higher (p<.05) in IPS as compared to CONT side of the UA in cows. However, PI and RI did not differ between IPS and CON arteries of uterus in cows. A very high and positive correlation (r=.89; p<.05) existed between the diameter of UA and BFVo starting from 1st to 8th months of gestation in IPS as well as CONT sides of UA. Moreover, TAMV was highly and positively correlated (r=.91; p<.05) with BFVe throughout the gestation. In conclusion, these haemodynamic changes in the UA could be used as a valuable validity tool to differentiate the compromised pregnancy in Bos indicus cows.

Role of first‐trimester umbilical vein blood flow in predicting large‐for‐gestational age at birth

To describe umbilical vein (UV) hemodynamics at 11 + 0 to 13 + 6 weeks of gestation in pregnancies delivering a large-for-gestational-age (LGA) neonate, and to build a multiparametric model, including pregnancy and ultrasound characteristics in the first trimester, that is able to predict LGA at birth. This was a matched case-control study, of singleton pregnancies that underwent ultrasound examination at 11 + 0 to 13 + 6 weeks for aneuploidy screening, at a single center over a 4-year period. Cases were women who delivered a neonate with birth weight (BW) > 90th centile for gestational age and sex, according to local birth-weight standards, while controls were those who delivered a neonate with BW ranging between the 10th and 90th centiles, matched for maternal and gestational age, at a ratio of 1:3. Each included case underwent Doppler assessment of the uterine arteries and UV, including measurement of its diameter, time-averaged maximum velocity (TAMXV) and UV blood flow (UVBF). UVBF and its components were expressed as Z-scores. Fisher's exact test and Mann-Whitney U-test were used to compare differences in maternal biomarkers and ultrasound characteristics between pregnancies complicated by LGA and controls. Logistic regression and receiver-operating-characteristics (ROC) curve analyses were carried out to identify independent predictors of LGA and to build a multiparametric prediction model integrating different maternal, pregnancy and ultrasound characteristics. Subgroup analysis was also performed, considering women who delivered a neonate with BW > 4000 g. In total, 964 pregnancies (241 with LGA at birth and 723 without) were included in the study. In LGA pregnancies compared with controls, UV-TAMXV Z-score (0.8 (interquartile range (IQR), 0.4-1.5) vs 0.0 (IQR, -0.3 to 0.5); P ≤ 0.001) and UVBF Z-score (1.3 (IQR, 0.8-1.9) vs 0.1 (IQR, -0.4 to 0.4); P ≤ 0.001) were higher, while there was no difference in median UV diameter Z-score (P = 0.56). Median uterine artery pulsatility index multiples of the median (MoM; 0.94 (IQR, 0.78-1.12) vs 1.02 (IQR, 0.84-1.19); P = 0.04) was significantly lower in LGA pregnancies. On multivariate logistic regression analysis, maternal body mass index (BMI; adjusted odds ratio (aOR), 1.2 (95% CI, 1.1-1.7); P < 0.001), parity (aOR, 1.4 (95% CI, 1.2-1.6); P < 0.001), pregnancy-associated plasma protein-A (PAPP-A) MoM (aOR, 1.1 (95% CI, 1.0-1.6); P = 0.04) and UVBF Z-score (aOR, 1.6 (95% CI, 1.1-1.9); P < 0.001) were associated independently with LGA. A multiparametric model integrating parity, BMI and PAPP-A MoM provided an area under the ROC curve (AUC) of 0.72 (95% CI, 0.67-0.76) for the prediction of LGA. The addition of UVBF Z-score to this model significantly improved the prediction of LGA provided by maternal and biochemical factors, with an AUC of 0.79 (95% CI, 0.75-0.83; P = 0.03). Similarly, the model incorporating UVBF Z-score predicted BW > 4000 g with an AUC of 0.83 (95% CI, 0.75-0.93). UVBF measured at the time of the 11-14-week scan is associated independently with, and is predictive of, LGA and BW > 4000 g. Adding measurement of UVBF to a multiparametric model that includes maternal (parity and BMI) and biochemical (PAPP-A) parameters improves the diagnostic accuracy of prenatal screening for LGA at birth. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Clinical and ultrasound variables for early diagnosis of septic acute kidney injury in bitches with pyometra

The aetiology of septic acute kidney injury (AKI) is not completely elucidated. Early identification of AKI in septic patients is considered to improve survival rate since it allows rapid treatment onset. We evaluated clinical, haematological, urinary, B-mode, spectral Doppler, and contrast-enhanced ultrasound variables in 20 bitches with pyometra as sepsis models and 12 healthy controls. All animals with pyometra presented some degree of renal damage on histological examination; however, sequential organ failure assessment (SOFA) classified only 40% cases with sepsis. AKI derived from systemic infection was identified in 57% of cases with hypoperfusion and in 22% with inflammation, being an affection of multifactorial origin. Among the evaluated parameters, urinary protein/creatinine ratio >0.15, serum albumin <2.94 mg/dL, time-averaged minimum velocity <21.5 cm/s, renal length/aorta diameter ratio >5.93, pulsatility index >1.53, haematocrit <45%, time-averaged maximum velocity <45.7 cm/s, haemoglobin <16 g/dL, leukocytes >12.53 × 103/uL, and cortical contrast peak intensity <69%, in the order of accuracy, are significant indicators of septic AKI with an accuracy >80%. Thus, AKI is a very prevalent condition in septic patients, derived mainly from changes in renal perfusion and inflammation. Additionally, reviewing the SOFA score parameters is suggested to identify renal failure.