Neuroprotective effect of placenta-derived mesenchymal stromal cells: role of exosomes.

We have established early-gestation chorionic villus-derived placenta mesenchymal stromal cells (PMSCs) as a potential treatment for spina bifida (SB), a neural tube defect. Our preclinical studies demonstrated that PMSCs have the potential to cure hind limb paralysis in the fetal lamb model of SB via a paracrine mechanism. PMSCs exhibit neuroprotective function by increasing cell number and neurites, as shown by indirect coculture and direct addition of PMSC-conditioned medium to the staurosporine-induced apoptotic human neuroblastoma cell line, SH-SY5Y. PMSC-conditioned medium suppressed caspase activity in apoptotic SH-SY5Y cells, suggesting that PMSC secretome contributes to neuronal survival after injury. As a part of PMSC secretome, PMSC exosomes were isolated and extensively characterized; their addition to apoptotic SH-SY5Y cells mediated an increase in neurites, suggesting that they exhibit neuroprotective function. Proteomic and RNA sequencing analysis revealed that PMSC exosomes contain several proteins and RNAs involved in neuronal survival and development. Galectin 1 was highly expressed on the surface of PMSCs and PMSC exosomes. Preincubation of exosomes with anti-galectin 1 antibody decreased their neuroprotective effect, suggesting that PMSC exosomes likely impart their effect via binding of galectin 1 to cells. Future studies will include in-depth analyses of the role of PMSC exosomes on neuroprotection and their clinical applications.-Kumar, P., Becker, J. C., Gao, K., Carney, R. P., Lankford, L., Keller, B. A., Herout, K., Lam, K. S., Farmer, D. L., Wang, A. Neuroprotective effect of placenta-derived mesenchymal stromal cells: role of exosomes.

A Decade of Experience with the Ovine Model of Myelomeningocele: Risk Factors for Fetal Loss.

INTRODUCTION: The ovine model is the gold standard large animal model of myelomeningocele (MMC); however, it has a high rate of fetal loss. We reviewed our experience with the model to determine risk factors for fetal loss. METHODS: We performed a retrospective review from 2009 to 2018 to identify operative factors associated with fetal loss (early fetal demise, abortion, or stillbirth). Operative risk factors included gestational age at operation, operative time, reduction of multiple gestations, amount of replaced amniotic fluid, ambient temperature, and method of delivery. RESULTS: MMC defects were created in 232 lambs with an overall survival rate of 43%. Of the 128 fetuses that died, 53 (42%) had demise prior to repair, 61 (48%) aborted, and 14 (11%) were stillborn. Selective reduction of multiple gestations in the same uterine horn was associated with increased fetal demise (OR 3.03 [95% CI 1.29-7.05], p = 0.01). Later gestational age at MMC repair and Cesarean delivery were associated with decreased abortion/stillbirth (OR 0.90 [95% CI 0.83-0.90], p = 0.03, and OR 0.37 [95% CI 0.16-0.31], p = 0.02), respectively. CONCLUSION: Avoiding selective reduction, repairing MMC later in gestation, and performing Cesarean delivery decreases the rate of fetal loss in the ovine MMC model.

Clamping trials prior to thoracostomy tube removal and the need for subsequent invasive pleural drainage.

BACKGROUND: There is little evidence supporting or refuting clamping trials, a period of clamping thoracostomy tubes prior to removal. We sought to evaluate whether clamping trials reduce the need for subsequent pleural drainage procedures. METHODS: We conducted a retrospective cohort study of trauma patients who underwent tube thoracostomy during 2009-2015. We compared patients who underwent clamping trials to those who did not, adjusting for confounders. The primary outcome was subsequent ipsilateral pleural drainage within 30 days. RESULTS: We evaluated 214 clamping trial and 285 control patients. Only two of 214 patients failed their clamping trial and none developed a tension pneumothorax [0.0% (95% CI 0.0-1.7%)]. Clamping trials were associated with fewer pleural drainage procedures [13 (6%) vs. 33 (12%); adjusted OR 0.41 (95% CI 0.20-0.84)]. CONCLUSIONS: A clamping trial prior to thoracostomy tube removal seems to be safe and was associated with less likelihood of a subsequent pleural drainage procedure.

Subcutaneous local anesthetic infusion could eliminate use of epidural analgesia after the Nuss procedure.

AIM: To compare outcomes of continuous subcutaneous infusion of local anesthetic and epidural analgesia following the Nuss procedure. PATIENTS & METHODS: A retrospective chart review compared patients managed with subcutaneous local anesthetic infusion (n = 12) versus thoracic epidural (n = 19) following the Nuss procedure from March 2013 to June 2015. RESULTS: There was no difference in hospital length of stay or days on intravenous narcotics. Epidural catheter placement prolonged operating room time (146.58 ± 28.30 vs 121.42 ± 21.98 min, p = 0.01). Average pain scores were slightly higher in the subcutaneous infusion group (3.72 ± 1.62 vs 2.35 ± 0.95, p = 0.02), but of negligible clinical significance. CONCLUSION: Continuous subcutaneous infusion of local anesthetic could eliminate the need for thoracic epidural for pain management after the Nuss procedure.

Intercostal nerve cryoablation versus thoracic epidural catheters for postoperative analgesia following pectus excavatum repair: Preliminary outcomes in twenty-six cryoablation patients.

BACKGROUND: Multimodal pain management strategies are used for analgesia following pectus excavatum repair. However, the optimal regimen has not been identified. We describe our early experience with intercostal cryoablation for pain management in children undergoing the Nuss procedure and compare early cryoablation outcomes to our prior outcomes using thoracic epidural analgesia. METHODS: A multi-institutional, retrospective review of fifty-two patients undergoing Nuss bar placement with either intercostal cryoablation (n=26) or thoracic epidural analgesia (n=26) from March 2013 to January 2016 was conducted. The primary outcome was hospital length of stay. Secondary outcomes included telemetry unit monitoring time, total intravenous narcotic use, duration of intravenous narcotic use, and postoperative complications. RESULTS: Patients who underwent intercostal cryoablation had a significant reduction in the mean hospital length of stay, time in a monitored telemetry bed, total use of intravenous narcotics, and the duration of intravenous narcotic administration when compared to thoracic epidural patients. Cryoablation patients had a slightly higher rate of postoperative complications. CONCLUSION: Intercostal cryoablation is a promising technique for postoperative pain management in children undergoing repair of pectus excavatum. This therapy results in reduced time to hospital discharge, decreased intravenous narcotic utilization, and has eliminated epidurals from our practice. LEVEL OF EVIDENCE: Retrospective study - level III.