Multi-disciplinary care in patients with complex pediatric general and thoracic surgical pathology: lessons learned from a 20-year experience.

PURPOSE: Complex pediatric surgery patients with thoracic tumors invading the mediastinum and infradiaphragmatic tumors extending into the chest are at risk for surgical morbidity and mortality if the patient's care is not coordinated. We sought to identify areas of focus when managing these patients to improve care. METHODS: A 20-year, retrospective study of pediatric patients with complex surgical pathology was performed. Demographic data, pre-operative characteristics, intraoperative data, complications, and outcomes data were collected. Three index cases were highlighted to provide granularity in patient management. RESULTS: Twenty-six patients were identified. Common pathology included mediastinal teratomas, foregut duplications, advanced Wilms tumors, hepatoblastoma, and lung masses. All cases were performed in a multidisciplinary fashion. All cases were done with pediatric cardiothoracic surgery and three cases (11.5%) required pediatric otolaryngology. Eight patients (30.7%) required cardiopulmonary bypass. Operative and 30-day mortality was zero. CONCLUSIONS: Management of complex pediatric surgical patients requires a multidisciplinary approach throughout the patient's hospital course. This multidisciplinary team should meet in advance of a patient's procedure to create a customized care plan that may include pre-operative optimization. At the time of their procedure, all necessary and emergency equipment should available. This approach improves patient safety and has resulted in excellent outcomes. LEVEL OF EVIDENCE: IV.

Understanding the burden of traumatic injuries at the United States-Mexico border: A scoping review of the literature.

ABSTRACT: The US-Mexico border is the busiest land crossing in the world and faces continuously increasing numbers of undocumented border crossers. Significant barriers to crossing are present in many regions of the border, including walls, bridges, rivers, canals, and the desert, each with unique features that can cause traumatic injury. The number of patients injured attempting to cross the border is also increasing, but significant knowledge gaps regarding these injuries and their impacts remain. The purpose of this scoping literature review is to describe the current state of trauma related to the US-Mexico border to draw attention to the problem, identify knowledge gaps in the existing literature, and introduce the creation of a consortium made up of representatives from border trauma centers in the Southwestern United States, the Border Region Doing Research on Trauma Consortium. Consortium members will collaborate to produce multicenter up-to-date data on the medical impact of the US-Mexico border, helping to elucidate the true magnitude of the problem and shed light on the impact cross-border trauma has on migrants, their families, and the US health care system. Only once the problem is fully described can meaningful solutions be provided.

Up and over: Consequences of raising the United States-Mexico border wall height.

OBJECTIVES: San Diego County's geographic location lends a unique demographic of migrant patients injured by falls at the United States-Mexico border. To prevent migrant crossings, a 2017 Executive Order allocated funds to increase the southern California border wall height from 10 ft to 30 ft, which was completed in December 2019. We hypothesized that the elevated border wall height is associated with increased major trauma, resource utilization, and health care costs. METHODS: Retrospective trauma registry review of border wall falls was performed by the two Level I trauma centers that admit border fall patients from the southern California border from January 2016 to June 2022. Patients were assigned to either "pre-2020" or "post-2020" subgroups based upon timing of completion of the heightened border wall. Total number of admissions, operating room utilization, hospital charges, and hospital costs were compared. RESULTS: Injuries from border wall falls grew 967% from 2016 to 2021 (39 vs. 377 admissions); this percentage is expected to be supplanted in 2022. When comparing the two subgroups, operating room utilization (175 vs. 734 total operations) and median hospital charges per patient ($95,229 vs. $168,795) have risen dramatically over the same time period. Hospital costs increased 636% in the post-2020 subgroup ($11,351,216 versus $72,172,123). The majority (97%) of these patients are uninsured at admission, with costs largely subsidized by federal government entities (57%) or through state Medicaid enrollment postadmission (31%). CONCLUSION: The increased height of the United States-Mexico border wall has resulted in record numbers of injured migrant patients, placing novel financial and resource burdens on already stressed trauma systems. To address this public health crisis, legislators and health care providers must conduct collaborative, apolitical discussions regarding the border wall's efficacy as a means of deterrence and its impact on traumatic injury and disability. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

Modified laparoscopic gastrostomy tube placement in children: Does subcutaneous suture type matter?

BACKGROUND: Laparoscopic gastrostomy tube (GT) placement carries the risk of early tube dislodgement and is often modified with absorbable subcutaneously-tunneled transabdominal tacking sutures that can aid in tube replacement. However, these buried sutures may increase the risk of surgical site infection (SSI). This study sought to evaluate SSI rates associated with different types of transabdominal tacking sutures used in modified laparoscopic GT placement. METHODS: A single-institution, retrospective review was performed of all patients ≤18 years-old undergoing modified laparoscopic GT placement between September 2016 and March 2020. Patients were stratified into three groups by suture type used, and the primary outcome was SSI within six weeks of surgery. Demographic and perioperative data were analyzed by chi-square or Fisher's exact test. RESULTS: A total of 113 modified laparoscopic GT placements were performed at a median age of 9 months (interquartile range 3 months to 3 years). Prophylactic antibiotic use was similar between groups. Eleven patients (10%) developed an SSI, and all were treated with antibiotics alone. No SSIs were observed with the use of poliglecaprone suture (n = 46), and higher SSI rates were observed with use of polyglactin (n = 17) and polydioxanone (n = 51) suture (18% polyglactin vs. 16% polydioxanone vs. 0% poliglecaprone, p<0.05). No differences were observed in rates of early postoperative dislodgement, leakage, or granulation tissue. CONCLUSION: Absorbable braided and long-lasting monofilament transabdominal tacking sutures may increase risk of SSI following modified laparoscopic gastrostomy tube placement. In this cohort, the use of poliglecaprone (Monocryl) suture was associated with no SSIs and similar rates of postoperative dislodgement, leakage, and granulation tissue. LEVEL OF EVIDENCE: Treatment Study, Level III.

Minimizing the risk of occupational Q fever exposure: A protocol for ensuring Coxiella burnetii-negative pregnant ewes are used for medical research.

Q fever is a worldwide zoonosis caused by Coxiella burnetii that can lead to abortion, endocarditis, and death in humans. Researchers utilizing parturient domestic ruminants, including sheep, have an increased risk of occupational exposure. This study evaluated the effectiveness of our screening protocol in eliminating C. burnetii-positive sheep from our facility. From August 2010 to May 2018, all ewes (N = 306) and select lambs (N = 272; ovis aries) were screened twice for C. burnetii utilizing a serum Phase I and Phase II antibody immunofluorescence assay (IFA). The first screen was performed by the vendor prior to breeding, and the second screen was performed on arrival to the research facility. Ewes that were positive on arrival screening were quarantined and retested using repeat IFA serology, enzyme-linked immunosorbent assay, buffy coat polymerase chain reaction (PCR), and amniotic fluid PCR. The overall individual seroprevalence of C. burnetii in the flocks tested by the vendor was 14.2%. Ewes with negative Phase I and Phase II IFA results were selected for transport to the research facility. Upon arrival to the facility, two (0.7%) ewes had positive Phase I IFA results. Repeat testing demonstrated seropositivity in one of these two ewes, though amniotic fluid PCR was negative in both. The repeat seropositive ewe was euthanized prior to use in a research protocol. No Q fever was reported among husbandry, laboratory or veterinary staff during the study period. Serologic testing for C. burnetii with IFA prior to transport and following arrival to a research facility limits potential exposure to research staff.

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.

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.

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.

Design of a cost-effective, hemodynamically adjustable model for resuscitative endovascular balloon occlusion of the aorta (REBOA) simulation.

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is an adjunct technique for salvaging patients with noncompressible torso hemorrhage. Current REBOA training paradigms require large animals, virtual reality simulators, or human cadavers for acquisition of skills. These training strategies are expensive and resource intensive, which may prevent widespread dissemination of REBOA. We have developed a low-cost, near-physiologic, pulsatile REBOA simulator by connecting an anatomic vascular circuit constructed out of latex and polyvinyl chloride tubing to a commercially available pump. This pulsatile simulator is capable of generating cardiac outputs ranging from 1.7 to 6.8 L/min with corresponding arterial blood pressures of 54 to 226/14 to 121 mmHg. The simulator accommodates a 12 French introducer sheath and a CODA balloon catheter. Upon balloon inflation, the arterial waveform distal to the occlusion flattens, distal pulsation within the simulator is lost, and systolic blood pressures proximal to the balloon catheter increase by up to 62 mmHg. Further development and validation of this simulator will allow for refinement, reduction, and replacement of large animal models, costly virtual reality simulators, and perfused cadavers for training purposes. This will ultimately facilitate the low-cost, high-fidelity REBOA simulation needed for the widespread dissemination of this life-saving technique.

Age Does Matter: A Pilot Comparison of Placenta-Derived Stromal Cells for in utero Repair of Myelomeningocele Using a Lamb Model.

INTRODUCTION: Fetal amniotic membranes (FM) have been shown to preserve spinal cord histology in the fetal sheep model of myelomeningocele (MMC). This study compares the effectiveness of placenta-derived mesenchymal stromal cells (PMSCs) from early-gestation versus term-gestation placenta to augment FM repair to improve distal motor function in a sheep model. METHODS: Fetal lambs (n = 4) underwent surgical MMC creation followed by repair with FM patch with term-gestation PMSCs (n = 1), FM with early-gestation PMSCs (n = 1), FM only (n = 1), and skin closure only (n = 1). Histopathology and motor assessment was performed. RESULTS: Histopathologic analysis demonstrated increased preservation of spinal cord architecture and large neurons in the lamb repaired with early-gestation cells compared to all others. Lambs repaired with skin closure only, FM alone, and term-gestation PMSCs exhibited extremely limited distal motor function; the lamb repaired with early-gestation PMSCs was capable of normal ambulation. DISCUSSION: This pilot study is the first in vivo comparison of different gestational-age placenta-derived stromal cells for repair in the fetal sheep MMC model. The preservation of large neurons and markedly improved motor function in the lamb repaired with early-gestation cells suggest that early-gestation placental stromal cells may exhibit unique properties that augment in utero MMC repair to improve paralysis.

Placental mesenchymal stromal cells rescue ambulation in ovine myelomeningocele.

UNLABELLED: Myelomeningocele (MMC)-commonly known as spina bifida-is a congenital birth defect that causes lifelong paralysis, incontinence, musculoskeletal deformities, and severe cognitive disabilities. The recent landmark Management of Myelomeningocele Study (MOMS) demonstrated for the first time in humans that in utero surgical repair of the MMC defect improves lower limb motor function, suggesting a capacity for improved neurologic outcomes in this disorder. However, functional recovery was incomplete, and 58% of the treated children were unable to walk independently at 30 months of age. In the present study, we demonstrate that using early gestation human placenta-derived mesenchymal stromal cells (PMSCs) to augment in utero repair of MMC results in significant and consistent improvement in neurologic function at birth in the rigorous fetal ovine model of MMC. In vitro, human PMSCs express characteristic MSC markers and trilineage differentiation potential. Protein array assays and enzyme-linked immunosorbent assay show that PMSCs secrete a variety of immunomodulatory and angiogenic cytokines. Compared with adult bone marrow MSCs, PMSCs secrete significantly higher levels of brain-derived neurotrophic factor and hepatocyte growth factor, both of which have known neuroprotective capabilities. In vivo, functional and histopathologic analysis demonstrated that human PMSCs mediate a significant, clinically relevant improvement in motor function in MMC lambs and increase the preservation of large neurons within the spinal cord. These preclinical results in the well-established fetal ovine model of MMC provide promising early support for translating in utero stem cell therapy for MMC into clinical application for patients. SIGNIFICANCE: This study presents placenta-derived mesenchymal stromal cell (PMSC) treatment as a potential therapy for myelomeningocele (MMC). Application of PMSCs can augment current in utero surgical repair in the well-established and rigorously applied fetal lamb model of MMC. Treatment with human PMSCs significantly and dramatically improved neurologic function and preserved spinal cord neuron density in experimental animals. Sixty-seven percent of the PMSC-treated lambs were able to ambulate independently, with two exhibiting no motor deficits whatsoever. In contrast, none of the lambs treated with the vehicle alone were capable of ambulation. The locomotor rescue demonstrated in PMSC-treated lambs indicates great promise for future clinical trials to improve paralysis in children afflicted with MMC.

Development of a locomotor rating scale for testing motor function in sheep.

BACKGROUND/PURPOSE: Research to cure paralysis associated with myelomeningocele (MMC) is ongoing using the fetal sheep model of MMC. Despite decades of research using this model, no standardized motor function assessment exists. The purpose of this study is to develop a sensitive and reliable locomotor scale for assessing the functional status of sheep. METHODS: Twenty lambs were used to develop and validate the locomotor scale. Lambs (n=15) underwent a surgically created MMC defect at gestational age (GA) 75 days, followed by repair with various methods at GA 100. One lamb underwent a sham operation (n=1). Normal lambs (n=4) served as controls. All lambs were born via spontaneous vaginal delivery, and motor function was assessed for 24 hours. A locomotor rating scale was developed based on behavioral observations of lambs. Inter-rater reliability testing was performed to determine if the scale could be reliably applied by different raters. RESULTS: Observations led to the definition of 7 categories of locomotor recovery. A scoring system was developed to rank these categories. The scale captured a wide variety of neurologic outcomes. Inter-rater reliability revealed minimal variability between examiners (average standard deviation ±0.431). The average score for all raters was within 1 point of the consensus score 100% of the time. CONCLUSIONS: The sheep locomotor rating scale is capable of capturing subtle differences in neurologic function with minimal inter-rater variability. We propose a standardized rating scale for neurologic outcomes and believe this is a critical component for assessing the validity of experimental treatments to cure paralysis in MMC.

Innate healing in the fetal sheep model of myelomeningocele: A standardized defect grading system.

BACKGROUND/PURPOSE: The fetal sheep model of myelomeningocele (MMC) is well-established. While the variability of innate fetal healing of the defect at the time of the repair operation has been acknowledged, it remains poorly described. We characterized the healing within the fetal sheep MMC model and present a standardized defect grading system. METHODS: Forty-three fetuses underwent surgical MMC creation at a gestational age of 75 days and repair at 100 days. Defects were graded based on percentage of exposed spinal cord and degree of scarring. A scale was developed and validated by interrater reliability testing. RESULTS: The phenotypic appearance of the defect at the time of the repair operation was highly variable. The defect length ranged from 3.0 to 5.5cm. Three spinal cords remained fully exposed across their length; 18 were completely covered in fibrinous exudate. Twenty-two fetuses demonstrated varying degrees of open spinal cord. Interrater reliability revealed consistent grades 91% of the time. CONCLUSION: Despite consistent defect creation, the fetal MMC defect has a wide spectrum of appearance at the time of the second surgery. This study describes the innate fetal healing within the model and presents a feasible and valid grading scale to ensure scientific rigor within the model.

Pregnancy-related attrition in general surgery.

IMPORTANCE: Residency attrition rates remain a great challenge for general surgery training programs. Despite the increasing acceptance of pregnancy during training, 1 common perception is that women who become pregnant are at increased risk of leaving surgery programs. OBJECTIVE: To determine whether child rearing increases the risk of attrition from general surgery residency. DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of all categorical general surgery residents in a single academic general surgery residency program over a 10-year period. All categorical general surgery residents matriculated from July 1, 1999, until July 1, 2009. MAIN OUTCOMES AND MEASURES: Voluntary attrition rate, involuntary attrition rate, and incidence of child rearing among residents. RESULTS: Eighty-five residents matched into categorical general surgery postgraduate year 1 spots from July 1, 1999, to July 1, 2009. Of the total residents, 49 (58%) were men while 36 (42%) were women. Attrition in the program was 18.8% (16 of 85). Seven (44%) of the residents who left the program were women; this was 19% of all female residents in the program. This was not significantly different from the proportion of men who left the program (P = .90). A higher percentage of women (57%) left after their intern year compared with men (22%). Furthermore, men had the highest rate of attrition during research (33%) while no women left during research years. Among the 85 residents, 9 women reported a total of 10 pregnancies and 16 men reported raising 21 children (1 woman and 1 man left the program). The proportion of child rearing was higher in those who did not leave the program but this did not reach significance (P = .10). Neither age (odds ratio, 1.0; 95% CI, 0.8-1.4), sex (odds ratio, 1.0; 95% CI, 0.2-3.6), nor incidence of child rearing during training (odds ratio, 1.0; 95% CI, 0.1-9.6) were associated with an increased risk of attrition. Residents with children born during training did not demonstrate fewer total case numbers (men, P = .40; women, P = .93) or board pass rates (men, P = .76; women, P = .50) compared with residents who did not have children during training. Women who had children during training were more likely to pursue fellowship (87.5%) than those who did not (66.7%)(P < .001). CONCLUSIONS AND RELEVANCE: The current study demonstrated there was no association between female sex and attrition at our institution. Child rearing did not appear to be a risk factor for attrition in either men or women. Furthermore, child rearing did not negatively impact the quality of training based on case numbers and board pass rates. Despite prevalent stereotypes, child rearing did not cause women or men to leave the program.