Fetal echocardiographic assessment of cardiovascular impact of prolonged support on EXTrauterine Environment for Neonatal Development (EXTEND) system.

OBJECTIVE: EXTrauterine Environment for Neonatal Development (EXTEND) is a system to support ongoing fetal growth and organ development in an extrauterine environment, utilizing a pumpless low-resistance oxygenator circuit. The aim of this study was to evaluate hemodynamics and cardiac function in fetal sheep sustained on the EXTEND system. METHODS: This was a prospective study of fetal sheep supported for a minimum of 3 weeks on EXTEND. Hemodynamic parameters were assessed weekly and included heart rate, mean arterial pressure (MAP), Doppler-echocardiography-derived cardiac output (CO), pulsatility indices (PIs) of the fetal middle cerebral artery (MCA), umbilical artery (UA) and ductus venosus and cardiac function, as assessed by speckle-tracking-derived global longitudinal strain and strain rate in the right (RV) and left (LV) ventricles. Parameters were compared at 0 days and 1, 2 and 3 weeks following placement on EXTEND. RESULTS: Of 10 fetal sheep enrolled, seven survived for 3 weeks and were included in the analysis. Median gestational age at cannulation was 107 (range, 95-109) days. Heart rate decreased and MAP increased significantly, but within acceptable ranges, during the study period. The quantities and relative ratios of right and left CO remained stable within the anticipated physiological range throughout the study period. Vascular tracings and PIs appeared to be similar to those seen normally in the natural in-utero state, with MCA-PI being higher than UA-PI. UA tracings demonstrated maintained abundant diastolic flow despite the absence of placental circulation. In both the RV and LV, strain decreased significantly at 1 and 2 weeks relative to baseline but returned to baseline values by week 3. CONCLUSIONS: The EXTEND mechanical support system replicates natural physiology and creates a stable and sustainable cardiovascular construct that supports growth over a 3-week period. However, there is a period of depressed contractility within the first week with subsequent improvement by week 3. This may reflect a period of physiological accommodation that warrants further investigation. This study lays the foundation for further exploration as the EXTEND system moves towards human application. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Sample entropy predicts lifesaving interventions in trauma patients with normal vital signs.

INTRODUCTION: Heart rate complexity, commonly described as a "new vital sign," has shown promise in predicting injury severity, but its use in clinical practice is not yet widely adopted. We previously demonstrated the ability of this noninvasive technology to predict lifesaving interventions (LSIs) in trauma patients. This study was conducted to prospectively evaluate the utility of real-time, automated, noninvasive, instantaneous sample entropy (SampEn) analysis to predict the need for an LSI in a trauma alert population presenting with normal vital signs. METHODS: Prospective enrollment of patients who met criteria for trauma team activation and presented with normal vital signs was conducted at a level I trauma center. High-fidelity electrocardiogram recording was used to calculate SampEn and SD of the normal-to-normal R-R interval (SDNN) continuously in real time for 2 hours with a portable, handheld device. Patients who received an LSI were compared to patients without any intervention (non-LSI). Multivariable analysis was performed to control for differences between the groups. Treating clinicians were blinded to results. RESULTS: Of 129 patients enrolled, 38 (29%) received 136 LSIs within 24 hours of hospital arrival. Initial systolic blood pressure was similar in both groups. Lifesaving intervention patients had a lower Glasgow Coma Scale. The mean SampEn on presentation was 0.7 (0.4-1.2) in the LSI group compared to 1.5 (1.1-2.0) in the non-LSI group (P < .0001). The area under the curve with initial SampEn alone was 0.73 (95% confidence interval [CI], 0.64-0.81) and increased to 0.93 (95% CI, 0.89-0.98) after adding sedation to the model. Sample entropy of less than 0.8 yields sensitivity, specificity, negative predictive value, and positive predictive value of 58%, 86%, 82%, and 65%, respectively, with an overall accuracy of 76% for predicting an LSI. SD of the normal-to-normal R-R interval had no predictive value. CONCLUSIONS: In trauma patients with normal presenting vital signs, decreased SampEn is an independent predictor of the need for LSI. Real-time SampEn analysis may be a useful adjunct to standard vital signs monitoring. Adoption of real-time, instantaneous SampEn monitoring for trauma patients, especially in resource-constrained environments, should be considered.

Randomized controlled trials affecting polytrauma care.

Trauma remains the leading cause of death in the world in patients under 45 years of age. The evaluation, resuscitation, and appropriate management of polytraumatized patients are paramount to successful outcomes. The advance of evidence-based medicine has had a powerful and positive impact on trauma care, even though the nature of many traumatic injuries lends itself poorly to study in a randomized fashion. During the initial management of bleeding patients, hypotensive resuscitation prior to surgical control has found strong support in the literature, and its use has been adopted by many surgeons. Head injury is the most common cause of traumatic death, and while high-level evidence is limited, adherence to management guidelines is associated with improved outcomes. For abdominal trauma, the concept of damage control surgery, while popular, has never been put to the test in a randomized controlled trial. Numerous randomized trials in the field of critical care have affected the management of severely injured patients, including intensive insulin therapy and low tidal volume ventilation in patients with compromised respiratory function. Finally, a multidisciplinary approach to trauma care in designated trauma centers allows for improved outcomes in polytraumatized patients.

Severe phenotype of a patient with autosomal recessive centronuclear myopathy due to a BIN1 mutation.

Centronuclear myopathy (CNM) is a rare hereditary congenital myopathy characterized by muscular hypotonia and abnormal centralization of nuclei in muscle fibers. The autosomal recessive (AR) form presents from birth to childhood, followed by a mild progression of muscle weakness. Despite recently identified genetic loci in the AR form, genotype-phenotype correlations are poorly established. Our index case is a 17 year old boy with recessive CNM causing loss of ambulation at 13 years of age and requiring ventilatory assistance nightly. Recent genetic testing revealed a c.1723A > T mutation in the BIN1 gene. The phenotype of the index case contrasts to previously published cases, where recessive CNM patients have lost ambulation in their 20s and have not required ventilatory assistance. The disease severity of our index case, carrying a c.1723A > T mutation, widens the phenotypic spectrum of AR CNM to include earlier loss of ambulation and respiratory failure.