Transcranial Ultrasound in the Neurocritical Care Unit.

Ultrasound evaluation of the brain is performed through acoustic windows. Transcranial Doppler has long been used to monitor patients with subarachnoid hemorrhage for cerebral vasospasm. Transcranial color-coded sonography permits parenchymal B-mode imaging and duplex evaluation. Transcranial ultrasound may also be used to assess the risk of delayed cerebral ischemia, screen patients for the presence of elevated intracranial pressure, confirm the diagnosis of brain death, measure midline shift, and detect ventriculomegaly. Transcranial ultrasound should be integrated with other point-of-care ultrasound techniques as an essential skill for the neurointensivist.

Factors influencing ultrasound cardiac output monitor waveform quality in patients admitted to the emergency intensive care unit.

Objective: The ultrasonic cardiac output monitor (USCOM), an instrument that monitors the evolution of a patient's hemodynamic status and determines the type of shock, has become an important tool for assessing cardiac pathology and predicting changes in disease, but there are some variations in the instrumental findings for different physical conditions of patients. This article examines whether there are differences in the quality of USCOM waveforms measured in different types of critically ill patients based on clinical characteristics and test parameters. Methods: Baseline data, diagnoses, echocardiograms, ventilation patterns, and USCOM results were retrospectively collected from patients in the emergency intensive care unit. Waveform quality was quantified using the Fremantle score to determine the extent to which age, body mass index (BMI), chronic obstructive pulmonary disease (COPD), respiratory failure, cardiac enlargement, valvular heart disease, and ventilation pattern influenced USCOM waveform quality. Results: Age, body mass index, chronic obstructive pulmonary disease, respiratory failure, right and left heart enlargement, aortic valve disease (excluding aortic stenosis), and ventilation mode did not have a significant effect on USCOM waveform quality in critically ill patients (P > 0.05). Conclusions: Various physical conditions of critically ill patients may have limited effect on the quality of the USCOM waveform, potentially rendering USCOM suitable for early assessment of hemodynamic status during ICU admission.

Cesarean Scar Ectopic Pregnancy: A Rare Case.

Cesarean scar ectopic pregnancy is one of the rarest of all ectopic pregnancies. Cesarean scar ectopic can occur after previous uterine manipulation, in vitro fertilization, hysterotomy, etc. With the increasing number of cesarean sections, the incidence of cesarean scar ectopics has increased worldwide. A high degree of suspicion over the occurrence of ectopic pregnancy after a cesarean section should be maintained by all healthcare workers. Timely diagnosis and treatment according to the presentation of an individual is of utmost importance. Here, we present a case of a 24-year-old second gravida with nine weeks of amenorrhea and a previous cesarean section presenting with the possibility of a scar ectopic, initially managed with medical management, followed by a planned laparotomy.

Aspirin administration from early pregnancy versus initiation after 11 weeks of gestation for prevention of pre-eclampsia in high-risk pregnant women: Study protocol for randomized controlled trial.

Background: Pre-eclampsia (PE) is a multiorgan disorder that affects 2-5% of all pregnant women. Present recommendations for when to start aspirin in high-risk women are after 11 wk of gestation. Objective: We present a protocol to investigate the effectiveness of aspirin use from early pregnancy, which is a randomized controlled trial to assess whether prescribed low-dose aspirin from early pregnancy reduces the prevalence of early and late-onset PE. Additionally, to compare the effectiveness of aspirin administration before and after 11 wk in reducing the occurrence of PE? Materials and Methods: All pregnancies at risk of PE, according to demographic and midwifery history, who are referred to the Maternal-Fetal Clinic of Tehran University hospital, Tehran, Iran were invited to take part in the trial. The outcomes of pregnancy and newborns will be gathered and analyzed. The first registration for the pilot study was in January 2023, and the participants were recognized as high-risk for PE. In addition, enrollment in the main study will begin as of October 2023.

Vascular resistance index and the immediate hemodynamic success of lower limb distal artery revascularization.

Background: Revascularization surgery is used to attempt to restore blood flow to the foot in patients with critical ischemia (CI) caused by peripheral arterial occlusive disease of the lower limbs (LL). Ultrasonography with Doppler (USD) SAH emerged in recent years as a highly valuable method for planning this surgical intervention. Objectives: To evaluate the relationship between the resistance index (RI), measured with USD, and immediate hemodynamic success of LL revascularization surgery in patients with CI. Methods: The study design was a prospective cohort assessing 46 patients with LL CLI who underwent operations to perform infrainguinal revascularization by angioplasty or bypass from August 2019 to February 2022. All patients underwent preoperative clinical vascular assessment with USD including measurement of the RI of distal LL arteries, LL arteriography, and measurement of the ankle-brachial index (ABI). All patients had their ABI measured again in the immediate postoperative period. Results: Forty-six patients were assessed, 25 (54.3%) of whom were male. Age varied from 32 to 89 years (mean: 67.83). Hemodynamic success was assessed by comparison of preoperative and postoperative ABI, showing that hemodynamic success was achieved in 31 (67.4%) patients after revascularization surgery (ABI increased by 0.15 or more). A positive correlation (p ≤ 0.05) was observed between the RI of the distal revascularized LL artery and immediate hemodynamic success assessed by ABI (lower RI and hemodynamic success). Conclusions: This study observed a positive correlation between the resistance index of the distal artery and immediate hemodynamic success of lower limb revascularizations, as assessed by the ankle-brachial index, so that the lower the RI the greater the hemodynamic success achieved.

What Is the Added Value of Carotid CEUS in the Characterization of Atherosclerotic Plaque?

Background and Objectives: Unstable atherosclerotic plaque in the arteries is one of the main risk factors for cerebral ischemia. Duplex ultrasound is a frequently used diagnostic method, but it has some limitations for microvascularization and neovascularization evaluation. The aim of this review was to evaluate the role of the new multiparametric US method-contrast-enhanced ultrasound (CEUS)-in atherosclerotic plaque instability verification. Materials and Methods: Original studies, reviews, and meta-analyses were included in this article. A total of 53 studies were retrieved; 29 were included in this study. Results: Carotid artery CEUS as a part of the multiparametric ultrasound method shows promising results and provides additional characteristics of soft- and high-risk atherosclerotic plaques; it can be advised in clinical practice for patients with carotid artery soft- and high-risk plaques. However, there are some limitations, such as extensive calcinosis with important acoustic shadows in carotid atherosclerotic plaque neovascularization diagnostics by CEUS. The added value of CEUS in the characterization of atherosclerotic plaque is that it indicates regions with high neovascularization and visualizes ulcerations on plaque surfaces, suggestive of increased instability risk.

Individual Patient Data Meta-Analysis of Dynamic Cerebral Autoregulation and Functional Outcome After Ischemic Stroke.

BACKGROUND: The relationship between dynamic cerebral autoregulation (dCA) and functional outcome after acute ischemic stroke (AIS) is unclear. Previous studies are limited by small sample sizes and heterogeneity. METHODS: We performed a 1-stage individual patient data meta-analysis to investigate associations between dCA and functional outcome after AIS. Participating centers were identified through a systematic search of the literature and direct invitation. We included centers with dCA data within 1 year of AIS in adults aged over 18 years, excluding intracerebral or subarachnoid hemorrhage. Data were obtained on phase, gain, coherence, and autoregulation index derived from transfer function analysis at low-frequency and very low-frequency bands. Cerebral blood velocity, arterial pressure, end-tidal carbon dioxide, heart rate, stroke severity and sub-type, and comorbidities were collected where available. Data were grouped into 4 time points after AIS: <24 hours, 24 to 72 hours, 4 to 7 days, and >3 months. The modified Rankin Scale assessed functional outcome at 3 months. Modified Rankin Scale was analyzed as both dichotomized (0 to 2 versus 3 to 6) and ordinal (modified Rankin Scale scores, 0-6) outcomes. Univariable and multivariable analyses were conducted to identify significant relationships between dCA parameters, comorbidities, and outcomes, for each time point using generalized linear (dichotomized outcome), or cumulative link (ordinal outcome) mixed models. The participating center was modeled as a random intercept to generate odds ratios with 95% CIs. RESULTS: The sample included 384 individuals (35% women) from 7 centers, aged 66.3±13.7 years, with predominantly nonlacunar stroke (n=348, 69%). In the affected hemisphere, higher phase at very low-frequency predicted better outcome (dichotomized modified Rankin Scale) at <24 (crude odds ratios, 2.17 [95% CI, 1.47-3.19]; P<0.001) hours, 24-72 (crude odds ratios, 1.95 [95% CI, 1.21-3.13]; P=0.006) hours, and phase at low-frequency predicted outcome at 3 (crude odds ratios, 3.03 [95% CI, 1.10-8.33]; P=0.032) months. These results remained after covariate adjustment. CONCLUSIONS: Greater transfer function analysis-derived phase was associated with improved functional outcome at 3 months after AIS. dCA parameters in the early phase of AIS may help to predict functional outcome.

Noninvasive Intracranial Pressure Monitoring: Are We There Yet?

There is an urgent unmet need for a reliable noninvasive tool to detect elevations in intracranial pressure (ICP) above guideline-recommended thresholds for treatment. Gold standard invasive ICP monitoring is unavailable in many settings, including resource-limited environments, and in situations such as liver failure in which coagulopathy increases the risk of invasive monitoring. Although a large number of noninvasive techniques have been evaluated, this article reviews the potential clinical role, if any, of the techniques that have undergone the most extensive evaluation and are already in clinical use. Elevations in ICP transmitted through the subarachnoid space result in distension of the optic nerve sheath. The optic nerve sheath diameter (ONSD) can be measured with ultrasound, and an ONSD threshold can be used to detect elevated ICP. Although many studies suggest this technique accurately detects elevated ICP, there is concern for risk of bias and variations in ONSD thresholds across studies that preclude routine use of this technique in clinical practice. Multiple transcranial Doppler techniques have been used to assess ICP, but the best studied are the pulsatility index and the Czosnyka method to estimate cerebral perfusion pressure and ICP. Although there is inconsistency in the literature, recent prospective studies, including an international multicenter study, suggest the estimated ICP technique has a high negative predictive value (> 95%) but a poor positive predictive value (≤ 30%). Quantitative pupillometry is a sensitive and objective method to assess pupillary size and reactivity. Proprietary indices have been developed to quantify the pupillary light response. Limited data suggest these quantitative measurements may be useful for the early detection of ICP elevation. No current noninvasive technology can replace invasive ICP monitoring. Where ICP monitoring is unavailable, multimodal noninvasive assessment may be useful. Further innovation and research are required to develop a reliable, continuous technique of noninvasive ICP assessment.

A Study on Clinico-Pathological Presentation and Management Prospective of Venolymphatic Malformation.

To evaluate the clinical perspective of Veno lymphatic malformation and definitive management in respect to outcome. (1) To discuss clinical presentation, symptomatology of Veno lymphatic malformation. (2) Demonstration of radiological features, diagnosis and management of Veno lymphatic malformation with its complication. This prospective study was conducted on four patients attending ENT-OPD of R.G.Kar Medical College, Kolkata, India who had presented with suspected vascular malformation. The study was conducted from March 2021 to March 2023 for a period of 2 years. The patients were subjected to detailed history and examination. The diagnosis of the Veno lymphatic malformation was based on the results of Doppler ultrasonography, computed tomography and magnetic resonance imaging. In our study there was male predominance. Most of the patients belonged to the 2nd and 3rd decade of life. The main sites of involvement were lateral neck followed by parotid region. The lesion size ranged in between 3.5 × 3.5 cm and 7 × 5 cm. The patient with parotid lesion was found to have phlebolith. Since most of the lesions were small with well-defined margins, we were able to excise the lesions completely without leaving any residue. Out of four cases one patient developed temporary paresis of spinal accessory nerve which resolved eventually. Veno lymphatic malformations are rare and there is no definitive protocol for management and to be individualized. Our study will be helpful for furthering the existing knowledge regarding the management of Veno lymphatic lesion emphasizing the need of multimodality approach in surgical decision making.

Supplementation with long-acting injectable progesterone 3 days after TAI impaired luteal function in buffaloes.

Three experiments were conducted to evaluate the effects of long-acting injectable progesterone (iP4) in buffalo cows. In Experiment 1, ovariectomized buffaloes received 300 mg (iP300) or 600 mg (iP600) of iP4, and serum P4 concentrations were evaluated. In experiment 2, three groups were compared: control or administration of 300 mg of iP4 3 (iP4-D3) or 6 days (iP4-D6) after timed artificial insemination (TAI). On day 16, reproductive tract was recovered for conceptus, endometrium, and corpus luteum (CL) analysis. In experiment 3, pregnancy per AI (P/TAI) and proportion of pregnancy losses were evaluated after administration of 300 mg of iP4 3 (iP4-D3) or 6 days (iP4-D6) after TAI in lactating buffaloes. In experiment 1, serum P4 concentrations remained over 1 ng/mL for ~ 3 days in both groups. The 300 mg dose was used in subsequent experiments. In experiment 2, CL weight and endometrial glands density were decreased, and conceptus length was increased in iP4-D3 compared to control and to iP4-D6 (P < 0.05). Transcript abundance of Prostaglandin F Receptor (FP) and ISG15 in CL and of ISG15 and MX1 in endometrium was greater in iP4-D3 when compared to control and to iP4-D6 (P < 0.05). In experiment 3, there was no difference among experimental groups for P/TAI at D30 and pregnancy losses (P > 0.1); however, iP4-D3 presented a lower P/TAI at day 60 (41.7%) when compared to control (56.8%) and iP4-D6 (57.7%; P = 0.07). In conclusion, administration iP4 at 3 days after TAI affects CL development and consequently decreases final pregnancy outcome in buffaloes.

Risk of Ovarian Malignancy Algorithm and Pelvic Mass Score for the prediction of malignant ovarian tumors: a prospective comparative study.

Aim: Ovarian cancer is the seventh most common female cancer worldwide. Nevertheless, there is no available universal screening method for malignant ovarian masses. This study compares the value of the Risk of Ovarian Malignancy Algorithm (ROMA) and Pelvic Mass Score (PMS) scoring systems in the diagnosis of malignant ovarian masses. Material and methods: This prospective comparative study was conducted from March 2021 until April 2022. A total of 258 women diagnosed with ovarian mass and eligible for surgical intervention according to institutional guidelines were enrolled in the study. Ultrasound was performed for the assessment of masses, ascites and metastases, also color flow Doppler was done to measure the resistance index of the mass vasculature. Preoperative venous blood samples were collected to measure CA 125 and HE4. PMS and ROMA scoring systems were calculated for each patient. All women were subjected to a surgical intervention (according to applicable institutional guidelines), using either open or laparoscopic techniques. Histopathological examination of the removed specimens was done, and in line with the recognized gold standard, the results were compared with the pre-operative diagnosis of both scoring systems. Results: Both PMS and ROMA showed a high predictive probability for ovarian malignancies (AUC = 0.93, sensitivity = 83.3%, specificity = 90.37%; AUC = 0.91, sensitivity = 84.4%, specificity = 95.56%, respectively), yet no statistical significant difference was found between the two scoring systems (p = 0.353, 95% CI -0.025 to 0.070). Conclusions: Both PMS and ROMA seem to be promising scoring systems for discriminating benign from malignant ovarian masses, but more research is needed to determine the optimum diagnostic pathway, especially one yielding the least false-negative results.

A Comparative Study of Transcranial Color-Coded Doppler (TCCD) and Transcranial Doppler (TCD) Ultrasonography Techniques in Assessing the Intracranial Cerebral Arteries Haemodynamics.

Cerebrovascular disease (CVD) poses a major public health and socio-economic burden worldwide due to its high morbidity and mortality rates. Accurate assessment of cerebral arteries' haemodynamic plays a crucial role in the diagnosis and treatment management of CVD. The study compared a non-imaging transcranial Doppler ultrasound (TCD) and transcranial color-coded Doppler ultrasound (with (cTCCD) and without (ncTCCD)) angle correction in quantifying middle cerebral arteries (MCAs) haemodynamic parameters. A cross-sectional study involving 50 healthy adults aged ≥ 18 years was conducted. The bilateral MCAs were insonated via three trans-temporal windows (TTWs-anterior, middle, and posterior) using TCD, cTCCD, and ncTCCD techniques. The MCA peak systolic velocity (PSV) and mean flow velocity (MFV) were recorded at proximal and distal imaging depths that could be visualised on TCCD with a detectable spectral waveform. A total of 152 measurements were recorded in 41 (82%) subjects with at least one-sided open TTW across the three techniques. The mean PSVs measured using TCD, ncTCCD, and cTCCD were 83 ± 18 cm/s, 81 ± 19 cm/s, and 93 ± 21 cm/s, respectively. There was no significant difference in PSV between TCD and ncTCCD (bias = 2 cm/s, p = 1.000), whereas cTCCD yielded a significantly higher PSV than TCD and ncTCCD (bias = -10 cm/s, p < 0.001; bias = -12 cm/s, p ≤ 0.001, respectively). The bias in MFV between TCD and ncTCCD techniques was (bias = -0.5 cm/s; p = 1.000), whereas cTCCD demonstrated a higher MFV compared to TCD and ncTCCD (bias = -8 cm/s, p < 0.001; bias = -8 cm/s, p ≤ 0.001, respectively). TCCD is a practically applicable imaging technique in assessing MCA blood flow velocities. cTCCD is more accurate and tends to give higher MCA blood flow velocities than non-imaging TCD and ncTCCD techniques. ncTCCD is comparable to non-imaging TCD and should be considered in clinical cases where using both TCD and TCCD measurements is needed.

Comparing Doppler Ultrasonography and Computerized Tomography Angiography in Emergency Department Evaluation of Earthquake-Related Crush Injuries: A Case Series Analysis.

OBJECTIVE: This case series aims to provide a comprehensive description of the utilization of doppler ultrasonography (USG) and computerized tomography angiography (CTA) in evaluating patients with earthquake-induced crush injuries in the emergency department (ED). METHODS: This retrospective case series was conducted on 11 patients who presented with crush injuries following a seismic event. These patients underwent initial assessment using doppler USG, with CTA performed when deemed necessary. Clinical outcomes and diagnostic findings were systematically reviewed. RESULTS: A cohort of 11 earthquake-related crush injury patients (six females, five males; age 3-59 years), predominantly with lower extremity injuries, with entrapped durations that ranged from 12 to 128 hours. Transport centers received patients from both affected regions and nearby provinces. Initial X-rays identified fractures in two cases. Doppler USG and subsequent CTA were employed for vascular evaluation, with CTA confirming doppler USG findings. Of the 11 patients, five exhibited abnormal doppler USG findings. Four patients required dialysis and four underwent amputation surgery. Fasciotomy and debridement procedures were performed in five and seven patients, respectively. Three patients received hyperbaric oxygen therapy (HBOT). CONCLUSION: Doppler USG emerged as a dependable tool for assessing vascular injuries in earthquake-related crush injuries, offering an effective alternative to CTA without the associated contrast agent risks. These findings underscore the need for further research to establish definitive imaging guidelines in these challenging clinical scenarios.

Testicular Torsion in the Undescended Testis of a Four-Year-Old: A Delayed Diagnosis.

In this report, we discuss the case of a four-year-old boy known to have global developmental delay (GDD) and infantile spasm. The child was brought to the emergency department (ER) with a tender inguinal swelling and fever. Notably, there was no previous indication of an undescended testicle (UDT), and the scrotum was not examined in the ER initially. The abdominal radiograph was unremarkable, and an ultrasound of the groin was requested to investigate the nature of the swelling. The ultrasound yielded a differential diagnosis of direct or indirect inguinal hernia containing intestinal loops or a necrotic lymph node. Ultimately, scrotal examination and repeated imaging confirmed the diagnosis of bilateral UDT with torsion and suspected infarction on the right side. Both UDT and testicular torsion (TT) are prevalent genitourinary disorders. However, the occurrence of torsion in an undescended testis is not commonly observed or documented, particularly within the age group presented in our case. TT is a surgical emergency, and its prognosis relies on early recognition and management in order to salvage the testis. In this case, there was a missed examination opportunity; therefore, it is imperative for emergency physicians to routinely include scrotal examination as part of the physical assessment when evaluating children with abdominal or groin pain in order to promptly identify such cases.

The effect of intrahepatic cholestasis of pregnancy and ursodeoxycholic acid treatment on Doppler parameters of fetal and maternal circulation.

OBJECTIVES: We aimed to evaluate feto-maternal blood flow parameters using Doppler ultrasonography (USG) in pregnant women with intrahepatic cholestasis of pregnancy (ICP) and the effect of ursodeoxycholic acid (UDCA) treatment on these parameters. MATERIAL AND METHODS: This prospective cohort study was performed at Dr. Sami Ulus Women's and Children's Health Teaching and Research Hospital, in Turkey between September 2022 and February 2023. Sixty pregnant women, 30 with ICP disease and 30 healthy women were included in the study. Obstetric Doppler parameters were measured by USG at diagnosis and after 48 hours of UDCA treatment for the ICP group. RESULTS: The obstetric Doppler parameters did not significantly differ in the ICP group and the healthy control group. The Doppler findings were similar after UDCA treatment in the ICP group. Gestational week at delivery and birth weight were lower in the ICP group in our study. CONCLUSIONS: We demonstrated that pregnant women with ICP had similar obstetric Doppler parameters when compared with healthy pregnant women and that the UDCA agent used for treatment of ICP disease did not affect these parameters.

Investigation of alterations in retrobulbar hemodynamics and their correlation with choroidal thickness after strabismus surgery.

BACKGROUND: To evaluate the changes in retrobulbar circulation after strabismus surgery and to assess the relationship of these changes with choroidal thickness (CT). METHODS: This prospective study included 26 eyes of 26 patients who underwent strabismus surgery and 15 eyes of 15 healthy individuals as control group. The patients who had single horizontal muscle surgery were included in Group 1 (n = 14); and those who had surgery on both horizontal muscles were included in Group 2 (n = 12). Peak systolic velocity (PSV), end-diastolic velocity (EDV), resistive index (RI) and pulsatility index (PI) of ophthalmic artery (OA), posterior ciliary artery (PCA), and central retinal artery (CRA) were measured using Color Doppler Ultrasonography. Subfoveal CT was measured via Optical Coherence Tomography. All measurements were obtained preoperatively, at 1st week and 1st month after surgery. RESULTS: There were no differences regarding preoperative blood flow velocity parameters among the groups. OA RI increased significantly at 1st week and 1st month after surgery in Group 1 and 2 (P = 0.029 and P = 0.045, respectively). There was a significant increase in PCA PSV at 1st week in Group 1 (P = 0.002). There was no difference between the mean preoperative and postoperative CT among the 3 groups. A negative correlation between the percentage changes of CT and CRA EDV was found in Group 2 (P = 0.011). CONCLUSION: Single and double horizontal rectus muscle surgery have a measurable effect on retrobulbar hemodynamics but these changes do not correlate with CT.

Diagnostic accuracy of CT and Doppler US for hepatic outflow obstruction after pediatric liver transplantation using left lobe or left lateral section grafts.

PURPOSE: The aim of this study was to evaluate diagnostic accuracy and to establish computed tomography (CT) and Doppler ultrasonography (US) criteria for hepatic outflow obstruction after pediatric liver transplantation (LT) using left lobe (LL) or left lateral section (LLS) grafts. METHODS: Pediatric patients who underwent LT using LL or LLS grafts between January 1999 and December 2021 were retrospectively included. The diagnostic performance of Doppler US and CT parameters for hepatic outflow obstruction was calculated using receiver operating characteristic (ROC) curve analysis. A diagnostic decision tree model combining the imaging parameters was developed. RESULTS: In total, 288 patients (150 girls; median age at LT, 1.8 years [interquartile range, 0.9 to 3.6 years]) were included. Among the Doppler US parameters, venous pulsatility index (VPI) showed excellent diagnostic performance (area under the ROC curve [AUROC], 0.90; 95% confidence interval [CI], 0.86 to 0.93; Youden cut-off value, 0.40). Among the CT parameters, anastomotic site diameter (AUROC, 0.92; 95% CI, 0.88 to 0.95; Youden cut-off, 4.2 mm) and percentage of anastomotic site stenosis (AUROC, 0.88; 95% CI, 0.84 to 0.92; Youden cut-off, 35%) showed excellent and good diagnostic performance, respectively. A decision tree model combining the VPI, peak systolic velocity, and percentage of anastomotic site stenosis stratified patients according to the risk of hepatic outflow obstruction. CONCLUSION: VPI, anastomotic site diameter, and percentage of anastomotic site stenosis were reliable imaging parameters for diagnosing hepatic outflow obstruction after pediatric LT using LL or LLS grafts.

Nutrient restriction during late gestation reduces milk yield and mammary blood flow in lactating primiparous beef females.

Fall-calving primiparous beef females [body weight (BW): 451 ±â€…28 (SD) kg; body condition score (BCS): 5.4 ±â€…0.7] were individually-fed 100% (control; CON; n = 13) or 70% (nutrient restricted; NR; n = 13) of estimated metabolizable energy and metabolizable protein requirements from day 160 of gestation to calving. Post-calving, all dams were individually-fed tall fescue hay supplemented to meet estimated nutrient requirements for maintenance, growth, and lactation until day 149 of lactation. Four-hour milk yields were collected on days 21, 42, 63, 84, 105, and 147 of lactation, and milk nutrient composition was determined. Doppler ultrasonography of both pudendoepigastric arterial trunks was conducted every 21 d from days 24 to 108 of lactation. Total mammary blood flow was calculated, and hemodynamics from both sides were averaged. Data were analyzed as repeated measures with nutritional plane, day of lactation, their interaction, calving date, and calf sex (if P < 0.25) as fixed effects. We previously reported that post-calving, NR dams weighed 64 kg less and were 2.0 BCS lower than CON, but calf birth weight was not affected. Milk weight and volume were 15% less (P = 0.04) for NR dams than CON. Milk protein concentration was lower (P = 0.008) for NR dams than CON, but triglyceride and lactose concentrations were not affected (P ≥ 0.20) by nutritional plane. Milk urea N concentration of NR dams tended to be greater (P = 0.07) on day 42 but was lower (P = 0.01) on day 147 of lactation than CON. Total milk protein, triglyceride, and lactose yields were less (P ≤ 0.05) for NR dams than CON. Total milk urea N yield was less (P ≤ 0.03) for NR dams than CON on days 21, 63, and 147 of lactation. Maternal heart rate was greater (P = 0.008), but pudendoepigastric arterial trunk peak systolic velocity, resistance index, and cross-sectional area were less (P ≤ 0.04) and pulsatility index tended to be less (P = 0.06) for NR dams than CON. Mammary blood flow was 19% less (P = 0.004) for NR dams than CON, but mammary blood flow relative to milk weight or dam BW was not affected (P ≥ 0.14) by nutritional plane. Most milk yield, milk nutrient composition, and mammary blood flow variables were affected (P ≤ 0.04) by day of lactation. In summary, first-parity beef females that were nutrient restricted during late gestation and then fed to meet estimated nutrient requirements during lactation had decreased milk nutrient yield and a similar reduction in mammary blood flow.

Mammary development in preparation for lactation is largely complete at the time of calving, and final prepartum mammary growth and differentiation are occurring for the first time in heifers. Nutrient requirements increase substantially during late gestation, resulting in competition for nutrient use among maternal growth, fetal growth, and mammary growth in primiparous beef females. Undernutrition during late gestation can occur due to poor forage nutrient availability or drought, potentially impacting mammary gland development and subsequent milk production. We report that first-parity beef females that were nutrient restricted during late gestation and then fed to meet estimated nutrient requirements during lactation had 15% lower milk yield, reduced milk protein concentration, and less total milk protein, triglycerides, lactose, and urea N available for their calves than controls. Additionally, previously nutrient restricted dams had 19% less total mammary blood flow, and the major arteries supplying the mammary gland were smaller.

Pharmacokinetics and pharmacodynamics of perfluoropropane after intra-venous bolus injection of perflutren lipid microsphere injection (DEFINITY®) in healthy Chinese volunteers.

BACKGROUND AND OBJECTIVE: Definity is an ultrasound contrast agent consisting of phospholipids-encapsulated perfluoropropane (PFP), also known as perflutren, microspheres, which is initially designed to enhance echocardiographic ultrasound images. With no pharmacologic action, Definity can increase the backscatter of ultrasound resulting enhanced ultrasound signals. The objective of this study was to determine the pharmacokinetics (PKs), Pharmacodynamics (PDs) and safety of Definity in healthy male and female Chinese volunteers. METHODS: A simple GC-MS method was developed and applied to simultaneously quantify PFP both in human whole blood and in expired air using Perfluorobutane (PFB) as internal standard. Meanwhile, the blood microbubble Doppler intensities were continuously monitored as companion PDs by a Doppler ultrasonography system using a non-imaging method. RESULTS: After intravenous infusion of 10 µL/kg of PFP within 30 seconds, the mean AUClast of the pharmacokinetic analysis set was 0.000653 (uL/mL)*min, the average AUC∞ was 0.001051 (uL/mL)*min. The main coefficient of variation of parameters were within 30%. In this trial, the blood drug concentration of female subjects was lower than that of males. Female Cmax, AUClast and AUC∞ were lower than males', Tmax and t1/2 was close to males', Vss and CL were slightly higher than males'. The concentration of PFP in the expired air of the subject reached the maximum value 1-2 min after administration and the PFP accumulation curve in the expired air began to become flat at 9.5-11 min after administration. The PFP in the expired air at the last sampling point of most subjects was still measurable. The results of the analysis showed that female subjects had slightly more and faster PFP excretion via the lungs than males. The change of blood drug concentration in this trial was related to the change process of Doppler signal intensity. The trend of the two was close, but the peak time of blood drug concentration was slightly delayed compared with the peak time of the Doppler signal intensity. The results showed that female tmax-pd, t10 was earlier than male, and women have lower AUCpd than men. CONCLUSION: The pharmacokinetics and pharmacodynamics of Definity in blood and expired air were systematically evaluated for the first time in this study. The PK/PD analysis results of this trial showed that the change of blood concentration was related to the change process of Doppler signal intensity, the trend of the two was close and expired air are the main excretion pathways of Definity. Definity was well tolerated by all subjects in the trial. TRIAL REGISTRATION: This study was registered on 08 December 2017 at the Chinese Clinical Trial Registry (CTR20171087).

Noninvasive Neuromonitoring Modalities in Children Part I: Pupillometry, Near-Infrared Spectroscopy, and Transcranial Doppler Ultrasonography.

BACKGROUND: Noninvasive neuromonitoring in critically ill children includes multiple modalities that all intend to improve our understanding of acute and ongoing brain injury. METHODS: In this article, we review basic methods and devices, applications in clinical care and research, and explore potential future directions for three noninvasive neuromonitoring modalities in the pediatric intensive care unit: automated pupillometry, near-infrared spectroscopy, and transcranial Doppler ultrasonography. RESULTS: All three technologies are noninvasive, portable, and easily repeatable to allow for serial measurements and trending of data over time. However, a paucity of high-quality data supporting the clinical utility of any of these technologies in critically ill children is currently a major limitation to their widespread application in the pediatric intensive care unit. CONCLUSIONS: Future prospective multicenter work addressing major knowledge gaps is necessary to advance the field of pediatric noninvasive neuromonitoring.