Evaluation of umbilical venous flow volume measured using ultrasound compared to circuit flow volume in the EXTra-uterine Environment for Neonatal Development (EXTEND) system in fetal sheep.

OBJECTIVE: To compare and validate umbilical venous flow volume (UVFV) measured at the intra-abdominal portion using ultrasound with actual flow volume of umbilical vein (UV) in fetal sheep sustained on the EXTrauterine Environment for Neonatal Development (EXTEND) system. METHODS: Circuit flow volume through the oxygenator was obtained using sensors. Ultrasound derived UVFV (ml/min) was calculated as (UV diameter [cm]/2)2 × 3.14 × maximum velocity (cm/s) × 0.5 × 60, measured at approximately the mid portion between its abdominal insertion and the origin of the ductus venosus. UVFV was measured by ultrasound once daily and was compared to the average of daily circuit flow volume directly measured. RESULTS: UVFV was measured 168 times in 15 fetal sheep. The ratio of circuit flow volume to combined cardiac output remained stable within the anticipated physiological range throughout. UVFV measured by ultrasound showed good correlation to directly measured circuit flow (r = 0.72). Interclass correlation coefficients for intra-observer variability was 0.991 (95% confidence interval [CI], 0.979-0.996). CONCLUSION: UVFV measured at the intra-abdominal portion using ultrasound shows a good correlation with directly measured circuit flow volume in UV of fetal sheep on the EXTEND system. Regular incorporation of such validated UVFV measures into clinical use may offer opportunities to better understand conditions of placental dysfunction.

Same-day discharge after laparoscopic appendectomy for non-perforated appendicitis is safe and cost effective.

AIM OF THE STUDY: To compare the outcomes and hospital charges of patients who underwent laparoscopic appendectomy for non-perforated appendicitis and were discharged home either shortly after the operation after being admitted for overnight observation. METHODS: Postoperative (30-day) emergency department (ED) visits, hospital readmissions, and reoperations were compared between patients who were discharged shortly after surgery (same-day discharge [SDD] group) and patients who were discharged after spending one night in the hospital (overnight observation group). STUDY PERIOD: July/2015 to June/2019. Patients with perforated appendicitis and/or who spent > 1 night in the hospital were excluded from the study. RESULTS: We did 1957 laparoscopic appendectomies within the 4-year study period. After excluding all non-eligible cases, 930 patients were included in the overnight observation group, and 511 in the SDD group. Mean age and mean operative time were similar in both groups: 11.5 (SD 3.6)/11.8 (SD 3.5) years, and 35 (SD 13)/33 (SD 12) minutes, respectively. There were 24 (2.6%) ED visits within the overnight observation group. Sixteen patients (1.7%) were discharged from the ED, and 8 (0.9%) required a re-admission. There were 11 (2.1%; P = 0.61) ED visits within the SDD group. Six patients (1.1%; P = 0.41) were discharged from the ED, and 5 (1%; P = 0.82) required a readmission. Six of the 11 ED visits within the SDD group occurred on the 5th postoperative day or later, whereas five (1%) occurred within the first 3 days post appendectomy. These five patients would have likely benefited from an overnight admission and were erroneously discharged on the same day of the appendectomy. There were no reoperations in the overnight observation group, but there were 3 reoperations in the SDD group (0.6%, P = 0.01). The reasons for the reoperations (two bowel obstructions and one bowel perforation) were in no way related to the time of the original discharge. The mean hospital charges per patient in the SDD group and the overnight observation group were significantly different: $32,450 and $35,420, respectively (> 9% margin, P < 0.01). CONCLUSION: Healthy children who undergo laparoscopic appendectomy for non-perforated appendicitis can be discharged home during the same day of the operation after a short period of observation. This approach is safe and does not result in more postoperative ED visits or hospital readmissions. In addition, there is a significant financial benefit when patients are discharged early. LEVEL-OF-EVIDENCE: Level III-retrospective comparative treatment study.

Technical feasibility of umbilical cannulation in midgestation lambs supported by the EXTra-uterine Environment for Neonatal Development (EXTEND).

EXTEND (EXTra-uterine Environment for Neonatal Development) is a novel system for supporting extremely premature infants that replicates in utero conditions by maintaining a sterile fluid environment and providing gas exchange via a pumpless arteriovenous oxygenator circuit connected to the umbilical vessels. Target gestational age (GA) for EXTEND support in human infants is 23-27 weeks, when immature lungs are most susceptible to injury in the setting of air ventilation. We previously demonstrated physiologic support of premature lambs cannulated at 105-117 days GA (lungs developmentally analogous to the 23-27 week GA human infant) for up to 28 days on EXTEND. In the present study, we sought to determine the technical feasibility of umbilical vessel cannulation in 85-96 days GA lambs delivered to EXTEND at weights equivalent to the 23-27 week GA human infant (500-850 g). Five preterm lambs were cannulated at 85-96 days GA (term 145 days) and supported on EXTEND for 4-7 days. All lambs underwent umbilical artery and umbilical vein cannulation. Circuit flows and pressures were monitored continuously, and blood gases were obtained at regular intervals for assessment of oxygen parameters. Systemic pH and lactate were measured at least once daily. Mean body weight at cannulation was 641 ± 71 g (range 480-850 g). All lambs were cannulated successfully (cannula size varied from 8 to 12 Fr), and mean survival on EXTEND was 140 ± 7 hours. Mean circuit flow was 213 ± 15 mL/kg*min, mean pH was 7.37 ± 0.01, and mean lactate was 1.6 ± 0.2 mmol/L. During the initial 120 hours after EXTEND cannulation, there were no significant differences between 85-96 days GA lambs and 105-117 days GA lambs in weight-adjusted circuit flows, oxygen delivery, pH, or lactate levels. This study demonstrates successful umbilical cord cannulation and adequate circuit flows and oxygen delivery in midgestation lambs size-matched to the 23-27 week GA human fetus, which represents an important step in the translation of EXTEND to clinical practice.

Erythropoietin Prevents Anemia and Transfusions in Extremely Premature Lambs Supported by an EXTrauterine Environment for Neonatal Development (EXTEND).

BACKGROUND: We recently developed an EXTrauterine Environment for Neonatal Development (EXTEND) that provides physiologic support for premature lambs. Here, we assess the efficacy of exogenous erythropoietin (EPO) to prevent anemia and transfusions on EXTEND. MATERIALS AND METHODS: Lambs were cannulated at 0.7 gestation and supported on EXTEND for up to 4 weeks. The lambs were divided into three groups: (1) No EPO, (2) Low EPO (300 U kg-1 per day), and (3) High EPO (800 U kg-1 per day). Daily hematocrit and weekly complete blood count were assessed. RESULTS: The mean percentage change in hematocrit from baseline was significantly different between the groups (No EPO -23.6 ± 7.8% vs. Low EPO -16.6 ± 6.4% vs. High EPO +2.6 ± 6.6%; p = 0.02). This occurred despite a greater median number of blood transfusions in the No EPO group (5 vs. 1 vs. 0; p = 0.02). EPO administration was associated with a higher mean corpuscular volume (MCV; p < 0.01) and reticulocyte count (p = 0.02). The High EPO group was comparable to in utero control fetuses with respect to hematocrit (p = 0.49), MCV (p = 0.24), and reticulocyte count (p = 0.68). CONCLUSIONS: EPO (800 U kg-1 per day) prevents anemia, eliminates transfusions, and restores normal red blood cell indices in premature lambs supported by EXTEND.

Umbilical cannulation optimizes circuit flows in premature lambs supported by the EXTra-uterine Environment for Neonatal Development (EXTEND).

KEY POINTS: Bronchopulmonary dysplasia is a disease of extreme prematurity that occurs when the immature lung is exposed to gas ventilation. We designed a novel 'artificial womb' system for supporting extreme premature lambs (called EXTEND) that obviates gas ventilation by providing oxygen via a pumpless arteriovenous circuit with the lamb submerged in sterile artificial amniotic fluid. In the present study, we compare different arteriovenous cannulation strategies on EXTEND, including carotid artery/jugular vein (CA/JV), carotid artery/umbilical vein (CA/UV) and umbilical artery/umbilical vein (UA/UV). Compared to CA/JV and CA/UV cannulation, UA/UV cannulation provided significantly higher, physiological blood flows to the oxygenator, minimized flow interruptions and supported significantly longer circuit runs (up to 4 weeks). Physiological circuit blood flow in UA/UV lambs made possible normal levels of oxygen delivery, which is a critical step toward the clinical application of artificial womb technology. ABSTRACT: EXTEND (EXTra-uterine Environment for Neonatal Development) is a novel system that promotes physiological development by maintaining the premature lamb in a sterile fluid environment and providing gas exchange via a pumpless arteriovenous oxygenator circuit. During the development of EXTEND, different cannulation strategies evolved with the aim of improving circuit flow. The present study examines how different cannulation strategies affect EXTEND circuit haemodynamics in extreme premature lambs. Seventeen premature lambs were cannulated at gestational ages 105-117 days (term 145-150 days) and supported on EXTEND for up to 4 weeks. Experimental groups were distinguished by cannulation strategy: carotid artery outflow and jugular vein inflow (CA/JV; n = 4), carotid artery outflow and umbilical vein inflow (CA/UV; n = 5) and double umbilical artery outflow and umbilical vein inflow (UA/UV; n = 8). Circuit flows and pressures were measured continuously. As we transitioned from CA/JV to CA/UV to UA/UV cannulation, mean duration of circuit run and weight-adjusted circuit flows increased (P < 0.001) and the frequency of flow interruptions declined (P < 0.05). Umbilical vessels generally accommodated larger-bore cannulas, and cannula calibre was directly correlated with circuit pressures and indirectly correlated with flow:pressure ratio (a measure of post-membrane resistance). We conclude that UA/UV cannulation in fetal lambs on EXTEND optimizes circuit flow dynamics and flow stability and also supports circuit flows that closely approximate normal placental flow.

Weight Nadir and Long-Term Weight Outcomes After Laparoscopic Sleeve Gastrectomy in a Diverse Cohort of Adolescents and Young Adults.

INTRODUCTION: Laparoscopic sleeve gastrectomy (LSG) is currently the most common bariatric procedure performed in adolescents and young adults in the United States (USA), but there are limited data available on long-term postoperative weight outcomes in these patients. This single-institution US study follows longitudinal weight data in a diverse group of patients undergoing LSG at age 25 years or younger. METHODS: We retrospectively reviewed records of all patients 25 years or younger who underwent LSG at our institution between 2013 and 2020. All weight data documented in the medical record through January 2023 was included. We calculated weight change postoperatively as percent total weight loss (%TWL) relative to preoperative weight. RESULTS: One hundred forty-one patients underwent LSG, at a mean age of 23.1 years. Within this cohort, 56.1% identified as non-Hispanic Black or Hispanic, and 39.7% had private health insurance. The mean %TWL at weight nadir was 28.5% at a mean of 1.35 years postoperatively. The mean long-term %TWL (in patients with ≥ 4 years of follow-up) was 11.8% at a mean of 5.6 years postoperatively, with 43 of the 84 patients with long-term weight data (51%) within 10% of their preoperative weight at most recent follow-up. CONCLUSION: Adolescents and young adults undergoing LSG at our institution had weight nadir comparable to published results during the first 1 to 2 years postoperatively, but the majority developed significant weight recurrence over the ensuing years. Our findings highlight the need for adjuvant weight loss strategies to improve the durability of weight outcomes after LSG in this population.

'Bovine' aortic arch - a marker for thoracic aortic disease.

OBJECTIVES: Very few studies have addressed the clinical significance of 'bovine' aortic arch (BA). We sought to determine whether BA is associated with thoracic aortic disease, including thoracic aortic aneurysm, aortic dissection, aortic rupture, and accelerated aortic growth rate. METHODS: We retrospectively reviewed CT and/or MRI scans of 612 patients with thoracic aortic disease and 844 patients without thoracic aortic disease to determine BA prevalence. In patients with thoracic aortic disease, we reviewed hospital records to determine growth rate, prevalence of dissection and rupture, and accuracy of radiology reports in citing BA. RESULTS: 26.3% of the patients with thoracic aortic disease had concomitant BA, compared to 16.4% of the patients without thoracic aortic disease (p < 0.001). There was no association between BA and prevalence of dissection or rupture (p = 0.38 and p = 0.56, respectively). The aortic expansion rate was 0.29 cm/year in the BA group and 0.09 cm/year in the non-BA group (p = 0.004). Radiology reports cited BA in only 16.1% of the affected patients. CONCLUSIONS: (1) BA is significantly more common in patients with thoracic aortic disease than in the general population. (2) Aortas expand more rapidly in the setting of BA. (3) Radiology reports often overlook BA. (4) BA should not be considered a 'normal' anatomic variant.

Cryptogenic acute lower extremities and multiorgan ischemia in an 8-year-old girl.

Pediatric acute limb ischemia is rare but can have devastating effects on children. The most common causes of acute limb ischemia in the pediatric age group are iatrogenic injury during cardiac catheterization and traumatic vessel injury. Embolic events have been described less often. We present the case of an 8-year-old girl with cryptogenic extensive bilateral lower extremity ischemia and embolization to multiple visceral organs. Our findings have highlighted the importance of interdisciplinary workup, timely intervention, and the advantage of intraoperative imaging for revascularization.

Neurologic outcomes of the premature lamb in an extrauterine environment for neonatal development.

BACKGROUND/PURPOSE: Neurologic injury remains the most important morbidity of prematurity. Those born at the earliest gestational ages can face a lifetime of major disability. Perinatal insults result in developmental delay, cerebral palsy, and other profound permanent neurologic impairments. The EXTracorporeal Environment for Neonatal Development (EXTEND) aims to transition premature neonates through this sensitive period, but it's impact on neurologic development requires analysis. METHODS: Fetal sheep were maintained in a fluid-filled environment for up to 28 days. Physiologic parameters were measured continuously; tissues were subsequently fixed and preserved for myelin quantification, glial cell staining, and structural assessment via magnetic resonance. Surviving animals were functionally assessed. RESULTS: No evidence of fetal brain ischemia or white matter tract injury associated with the EXTEND system was detected, and the degree of myelination was regionally appropriate and consistent with age matched controls. No evidence of neurologic injury or immaturity was visible on magnetic resonance; animals that transitioned from the system had no persistent neurologic deficits. CONCLUSIONS: No evidence of major neurologic morbidity was found in animals supported on the EXTEND system, though more work needs to be done in order to verify its safety during critical periods of neurologic development.

Pumpless arteriovenous extracorporeal membrane oxygenation: A novel mode of respiratory support in a lamb model of congenital diaphragmatic hernia.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is commonly required in neonates with congenital diaphragmatic hernia (CDH) complicated by pulmonary hypertension (PH). ECMO carries significant risk, and is contraindicated in the setting of extreme prematurity or intracranial hemorrhage. Pumpless arteriovenous ECMO (P-ECMO) may represent an alternative for respiratory support. The present study summarizes our initial experience with P-ECMO in a lamb model of CDH. STUDY DESIGN: Surgical creation of CDH was performed at 65-75days' gestation. At term (135-145days), lambs were delivered into the P-ECMO circuit. Three animals were maintained on a low-heparin infusion protocol (target ACT 160-180) and three animals were maintained with no systemic heparinization. RESULTS: Animals were supported by the circuit for 380.7 +/- 145.6h (range, 102-504h). Circuit flow rates ranged from 97 to 208ml/kg/min, with adequacy of organ perfusion demonstrated by stable serum lactate levels (3.0 +/- 1.7) and pH (7.4 +/- 0.3). Necropsy demonstrated no evidence of thrombogenic complications. CONCLUSION: Pumpless extracorporeal membrane oxygenation achieved support of CDH model lambs for up to three weeks. This therapy has the potential to bridge neonates with decompensated respiratory failure to CDH repair with no requirement for systemic anticoagulation, and may be applicable to patients currently precluded from conventional ECMO support.

An EXTrauterine environment for neonatal development: EXTENDING fetal physiology beyond the womb.

Extreme prematurity is a major cause of neonatal mortality and morbidity, and remains an unsolved clinical challenge. The development of an artificial womb, an extrauterine system recreating the intrauterine environment, would support ongoing growth and organ maturation of the extreme preterm fetus and would have the potential to substantially improve survival and reduce morbidity. Previous efforts toward the development of such a system have demonstrated the ability to maintain the isolated fetus for short periods of support, but have failed to achieve the long-term stability required for clinical application. Here we describe our initial experiments demonstrating the stable support of fetal lambs developmentally equivalent to the extreme premature infant for up to four weeks with stable hemodynamics, growth, and development. The achievement of long-term physiologic support of the fetus in an extrauterine system has the potential to fundamentally change the management and clinical outcome of the extreme premature infant.

Corrigendum: An extra-uterine system to physiologically support the extreme premature lamb.

This corrects the article DOI: 10.1038/ncomms15112.

An extra-uterine system to physiologically support the extreme premature lamb.

In the developed world, extreme prematurity is the leading cause of neonatal mortality and morbidity due to a combination of organ immaturity and iatrogenic injury. Until now, efforts to extend gestation using extracorporeal systems have achieved limited success. Here we report the development of a system that incorporates a pumpless oxygenator circuit connected to the fetus of a lamb via an umbilical cord interface that is maintained within a closed 'amniotic fluid' circuit that closely reproduces the environment of the womb. We show that fetal lambs that are developmentally equivalent to the extreme premature human infant can be physiologically supported in this extra-uterine device for up to 4 weeks. Lambs on support maintain stable haemodynamics, have normal blood gas and oxygenation parameters and maintain patency of the fetal circulation. With appropriate nutritional support, lambs on the system demonstrate normal somatic growth, lung maturation and brain growth and myelination.

Rectal diazepam gel in the home management of seizures in children.

This study assessed the utility of rectal diazepam gel in the home management of prolonged or repetitive seizures in children. Thirty-eight children being prescribed rectal diazepam gel by their clinician were prospectively recruited. Seizures, rectal diazepam use, emergency department visits, and quality of life data before and after study entry were recorded. The 38 children included 14 (37%) with complex febrile seizures, and 24 with epilepsy (n = 22) or a single seizure (n = 2). There were 23 (61%) children with prolonged seizures and 15 (39%) with repetitive seizures. During the 6-month follow-up period, 12 children experienced 26 seizures which met the criteria for rectal diazepam administration. Rectal diazepam gel was administered to 8 children on 19 occasions. In 16 (84%) of these episodes, seizures stopped and no emergency department visit was required. Parental stress was decreased between baseline and 6 months in both the overall group and in all the subgroups. Home use of rectal diazepam gel is effective in aborting seizure activity, often avoiding an emergency department visit. Its use reduces morbidity and costs associated with hospital visits and provides parents a treatment option for home management of prolonged or repetitive seizures.

Guilt by association: paradigm for detecting a silent killer (thoracic aortic aneurysm).

Recent studies have confirmed a close association between various medical conditions (intracranial aneurysm, abdominal aortic aneurysm, temporal arteritis, autoimmune disorder, renal cysts), certain aortic anatomic variants (bovine aortic arch, direct origin of left vertebral artery from aortic arch, bicuspid aortic valve), and family history of aneurysm disease with thoracic aortic aneurysm and dissection. This paper reviews these associations. We propose to capitalise on these associations as powerful and expanding opportunities to diagnose the virulent but silent disease of thoracic aortic aneurysm. This can be accomplished by recognition of this 'guilt by association' with the other conditions. Thus, patients with associated diseases and anatomic variants should be investigated for silent aortic aneurysms. Such a paradigm holds substantial potential for reducing death from the silent killer represented by thoracic aortic aneurysm disease.

Nonresectional single-suture leaflet remodeling for degenerative mitral regurgitation facilitates minimally invasive mitral valve repair.

BACKGROUND: Both leaflet resection and neochordal construction are effective mitral repair techniques, but they may become incrementally time-consuming when using minimally invasive approaches. We have used a single-suture leaflet-remodeling technique of inverting the prolapsed or flail segment tissue into the left ventricle. This repair is straightforward, expeditious, and facilitates a minimally invasive approach. METHODS: Ninety-nine patients with degenerative mitral regurgitation (MR) underwent a minimally invasive single-suture repair of the mitral valve from May 2007 through December 2012. Preoperative and perioperative echocardiograms as well as patient outcomes were analyzed and compared with those obtained from patients undergoing minimally invasive mitral valve repair using quadrangular resection at the same institution during the same period. RESULTS: All 99 patients had a successful mitral repair through a sternal-sparing minimally invasive approach. Ninety-one of the 99 patients had zero MR on postoperative echocardiogram, and 8 of 99 had trace to mild MR. Patients in the nonresectional group had significantly shorter cardiopulmonary bypass and cross-clamp times compared with the quadrangular resection group (115.8 ± 41.7 minutes versus 144.9 ± 38.2 minutes; p < 0.001; 76.2 ± 28.1 minutes versus 112.6 ± 33.5 minutes; p < 0.001, respectively). The mean length of stay was 7.5 ± 3 days. All patients were discharged alive and free from clinical symptoms of MR. There have been no reoperations for recurrent MR on subsequent average follow-up of 1 year. CONCLUSIONS: An effective, highly efficient, and thus far durable single-suture mitral leaflet-remodeling technique facilitates minimally invasive repair of degenerative MR.